PMID- 4014225 TI - Histidine-rich glycoprotein and changes in the components of the fibrinolytic system after streptokinase therapy in patients with pulmonary thromboembolism. AB - Although the biological function of histidine-rich glycoprotein (HRG) is unknown, it may serve as an antifibrinolytic agent by interfering with the binding of plasminogen to fibrin. To define the role of HRG, plasma titers were measured by single radial immunodiffusion in eleven patients with thromboembolism before and after streptokinase (SK) therapy and were found unchanged (84.7 +/- 6.2%, M +/- SEM before, and 99.5 +/- 6.3% after 12 hr of SK therapy). The HRG peaks on crossed immunoelectrophoresis before and after SK infusion were also unchanged. Alpha 2-plasmin inhibitor fell during SK infusion as measured immunologically (102.0 +/- 15.0% before and 28.0 +/- 1.6% after 12 hr of therapy) and fibrinogen fibrin degradative products appeared (mean titer of 1:2,048 after 12 hr of therapy), indicating that the infused SK was biologically active. Plasminogen levels before therapy were normal, as measured functionally and immunologically (105.4 +/- 4.9% and 96.0 +/- 5.6%, respectively), and both decreased after 12 hr of SK therapy (15.2 +/- 5.6% and 50.8 +/- 4.3%). No changes in functional antithrombin III titer, Hageman factor antigen level, or fibrinogen concentration, as measured turbidimetrically, were observed. Thus, although these data do not allow one to make any firm conclusions regarding the physiologic role of this protein in fibrinolysis, they do not exclude its increased catabolism, compensated by increased production, in patients undergoing fibrinolytic therapy. PMID- 4014226 TI - Treatment of hemophilic arthritis with D-penicillamine: a preliminary report. AB - Current medical management programs for established joint diseases in hemophiliacs are unsatisfactory and do not modify the eventual outcome. D penicillamine, a drug effective in the proliferative synovitis of rheumatoid arthritis, was evaluated in a rabbit model of hemarthroses-induced arthritis and in four hemophiliacs with chronic synovitis. The animals had intra-articular injections of citrate (left knees) and autologous citrated whole blood (right knees). Eight weeks later, the rabbits were divided into two groups: no treatment and D-penicillamine (50 mg/kg/day, IM) until sacrificed at 6 months. The saline injected joints showed no inflammation and no iron deposition. The blood-injected knees showed iron deposition in both groups, the D-penicillamine animals had marked suppression of chronic inflammation. Of the four patients treated, three had clinical responses (reduction in synovial thickness, reduction in number of bleeds in the affected joint). One patient, who did not respond, developed mild moderate proteinuria. Those patients who responded received between 5.3 and 7.1 mg/kg/day of the drug. Mild abnormalities in platelet aggregation were seen in the responders. This preliminary study suggests that D-penicillamine is beneficial in the chronic synovitis/arthritis induced by hemarthroses. Further trials are recommended. PMID- 4014227 TI - Obstructive jaundice from hepatic amyloidosis in a patient with multiple myeloma. AB - A patient with multiple myeloma is described who developed severe intrahepatic cholestasis secondary to hepatic deposition of amyloid. This is the first reported case of this complication's developing in a patient with multiple myeloma. PMID- 4014228 TI - Autoimmune hyperthyroidism and thrombocytopenia developing in a patient with chronic lymphocytic leukemia. AB - A 56-year-old white man is described whose course of chronic lymphocytic leukemia (CLL) was complicated by the occurrence of the autoimmune hyperthyroidism/thrombocytopenia syndrome. The implications of this syndrome on the treatment of CLL are discussed. PMID- 4014229 TI - Pharmacoepidemiology: emerging roles for pharmacists. PMID- 4014230 TI - Demonstrating mutagenicity using the Ames test. PMID- 4014231 TI - College of pharmacy-teaching hospital relationships: building strength. AB - Perhaps the most important factor to focus on is that organizations work because of the people in them; also, they don't work because of the people in them. Perhaps some people in some of our organizations need changing. Hospitals and colleges face similar issues that need to be worked on together. The philosophy of collaboration needs adopting because competition will not provide the success desired by the college or the hospital. Without a strong commitment on the part of decision makers, time and effort will be wasted. There must be an active process. It can't be talked about only once a year. There should also be an ongoing, active process at the national level. We must build on our mutual needs. We must use positive approaches rather than developing more negative arguments. The key to success is to concentrate more heavily on communications, visibility, and accountability. F. Scott Fitzgerald put it this way: The test of a first-rate intelligence is the ability to hold two opposed ideas in mind at the same time and still retain the ability to function. We have three ideas that at times are in opposition. Service, education, and research can be integrated by applying the intelligence found in every teaching hospital and college of pharmacy. PMID- 4014232 TI - National audit of drug information centers. AB - A comprehensive audit of drug information centers (DICs) was conducted to obtain information on sources of funding, staffing, information resources, computerization, workload, and scope of services and activities and to examine the role of DICs in education, patient care, and research. Responses were obtained from 98 of the 121 DICs surveyed. The scope of activities and services varied considerably between centers and depended on such factors as source of funding, size of institution, academic affiliation, staffing, and workload. Many DICs are involved in writing newsletters, preparing information for pharmacy and therapeutics committee meetings, developing and updating formularies, and providing contract services to other organizations. The patient-care activities of DICs include providing consultations, performing drug-use reviews, monitoring adverse drug reactions, and coordinating investigational drug studies; DICs are also involved in training undergraduate and graduate pharmacy students and residents and conducting research projects. Large workloads and lack of time were cited most often as factors limiting DIC participation in patient-care, educational, and research activities. Because DICs are involved in a wide variety of educational, research, and patient-care activities, more emphasis should be placed on documenting the costs of these services in relation to their benefits to the institution. PMID- 4014233 TI - Managing employee apprehension toward handling cytotoxic drugs. AB - A strategy for dealing with employee apprehension about handling cytotoxic agents without a biological safety cabinet is described. Available evidence in the literature concerning the health risks of handling cytotoxic drugs was reviewed with employees. A committee was appointed to evaluate the institution's needs and current practices for handling cytotoxic agents. Airflow studies were conducted in the pharmacy department's sterile preparation areas, and policies and procedures were developed for use until biological safety cabinets could be installed. Plans were developed for dealing with special situations, such as exemption of certain employees from preparation of cytotoxic drugs or refusal of an employee to prepare these drugs. Managers can substantially reduce employees' apprehension about handling cytotoxic drugs by keeping employees informed about departmental plans, listening to their concerns, and developing procedures for safe handling of these agents. PMID- 4014234 TI - Twenty-four hour emergency pharmaceutical services. AB - Operation of an emergency department satellite pharmacy in which the pharmacist provided clinical, educational, and drug distribution services during patient visits is described. In a Detroit trauma and ambulatory-care center, drugs were dispensed to outpatients 24 hours a day from a satellite pharmacy located in the 75-bed emergency department. Emergency department pharmaceutical services were expanded to include distributive, clinical, and educational activities by the pharmacist on a 24-hour basis. The pharmacist contributed to improved inventory control and billing for drug products. When reductions in the work force were necessary, the institution chose to retain 24-hour pharmacist coverage during emergency department patient visits and to eliminate 24-hour dispensing to outpatients. In this urban trauma center, the emergency department pharmacist's clinical, distributive, and educational services contributed substantially to delivery of patient care. PMID- 4014235 TI - Decision analysis applied to the purchase of frozen premixed intravenous admixtures. AB - A structured decision-analysis model was used to evaluate frozen premixed cefazolin admixtures. Decision analysis is a process of stating the desired outcome, establishing and weighting evaluation criteria, identifying options for reaching the outcome, evaluating and numerically ranking each option for each criterion, multiplying the ranking by the weight for each criterion, and calculating total points for each option. It was used to compare objectively frozen premixed cefazolin admixtures with batch reconstitution from vials and reconstitution of lyophilized, ready-to-mix containers. In this institution the model numerically demonstrated a distinct preference for the premixed frozen admixture over these other alternatives. A comparison of these results with the total cost impact of each option resulted in a decision to purchase the frozen premixed solution. The advantages of the frozen premixed solution that contributed most to this decision were decreased waste and personnel time. The latter was especially important since it allowed for the reallocation of personnel resources to other potentially cost-reducing clinical functions. Decision analysis proved to be an effective tool for formalizing the process of selecting among various alternatives to reach a desired outcome in this hospital pharmacy. PMID- 4014236 TI - Compatibility of clindamycin phosphate with cefotaxime sodium or netilmicin sulfate in small-volume admixtures. AB - The stability and compatibility of clindamycin phosphate plus either cefotaxime sodium or netilmicin sulfate in small-volume intravenous admixtures were studied. Admixtures containing each drug alone and two-drug admixtures of clindamycin phosphate plus cefotaxime sodium or netilmicin sulfate were prepared in 100 mL of 5% dextrose injection and 0.9% sodium chloride injection in both glass bottles and polyvinyl chloride (PVC) bags. Final concentrations of clindamycin, cefotaxime, and netilmicin were 9, 20, and 3 mg/mL, respectively. All solutions were prepared in duplicate and stored at room temperature (24 +/- 2 degrees C). Samples were visually inspected, tested for pH, and assayed for antibiotic concentration using stability-indicating assays at 0, 1, 4, 8, 16, and 24 hours for admixtures in glass bottles and at 0, 8, and 24 hours for admixtures in PVC bags. No substantial changes in color, clarity, pH, or drug concentration were observed in any of the solutions. Clindamycin phosphate is compatible with cefotaxime sodium or netilmicin sulfate in 5% dextrose and 0.9% sodium chloride injections in glass bottles or PVC bags for 24 hours. PMID- 4014237 TI - Advice of manufacturers about effects of temperature on biologicals. AB - Information was obtained from manufacturers on the stability of biologicals when exposed to higher-than-recommended temperatures, and procedures were developed for determining whether the quality of these products is compromised after such exposure. Questionnaires were sent to 24 manufacturers asking for product information regarding stability of frozen biologicals exposed to refrigeration or room temperature, stability of refrigerated biologicals exposed to room temperature, shelf life under optimal conditions, and recommended transport temperature. Information was provided by 20 of the manufacturers. Some manufacturers declined to make general recommendations; instead, they stated that the manufacturer should be contacted regarding the individual situation. The responses indicated that most products do not require freezing for storage and transport. Most must be stored refrigerated but can be transported at room temperature. Use of manufacturers' stability recommendations can help the pharmacist determine whether biologicals are of an acceptable quality for patient use. PMID- 4014239 TI - Two approaches to cost containment in hospital pharmacy. PMID- 4014238 TI - Repercussions of the Drug Price Competition and Patent Term Restoration Act of 1984. AB - Recently enacted legislation involving patent terms and the approval of new generic equivalent drug products is described, and the law's potential repercussions are discussed. The Drug Price Competition and Patent Term Restoration Act of 1984 (PL 98-417) consists of two titles that affect introduction procedures and patent requirements for certain types of generic new drug products. Title I allows drug manufacturers to use an abbreviated new drug application when seeking approval to make generic copies of drug products that were approved by the FDA after 1962. Title II encourages drug manufacturers to assume the increased costs of research and development of certain products that were subject to premarketing clearance by restoring some of the time lost on patent life while the product was awaiting FDA approval. Legislative analysts continue to question whether the short-term gains of eased market access to the generic manufacturers will be outweighed by the long-term benefits of patent extensions to the pioneer drug companies. The potential difficulties in the implementation of the Act and unresolved questions of law surrounding the new law are discussed. The possible effects of the new law on the drug manufacturing industry and market composition are described. Since PL 98-417 was implemented in September 1984, little has been settled in the way of implementing its provisions or accurately measuring its nonregulatory impact. It seems certain that the bill will be difficult to regulate and that litigation will proliferate. Furthermore, the impact of the statute on the composition of the drug industry will undoubtedly be substantial. PMID- 4014241 TI - Computer help for missing doses and refills. PMID- 4014240 TI - Physician perception of a triplicate prescription law. PMID- 4014242 TI - Using fluorescence of antineoplastic agents to demonstrate proper handling technique. PMID- 4014243 TI - Reporting problems about medical devices. PMID- 4014244 TI - Directions for clinical practice in pharmacy. Proceedings of an invitational conference conducted by the ASHP Research and Education Foundation and the American Society of Hospital Pharmacists. February 10-13, 1985. PMID- 4014245 TI - Pharmacy as a clinical profession. PMID- 4014246 TI - Panel discussion on realities of contemporary practice. PMID- 4014247 TI - Practitioner-educator coalition for reprofessionalizing an occupation. PMID- 4014248 TI - Practice perspective on practitioner-educator relationships. PMID- 4014249 TI - Building our image as a clinical profession. PMID- 4014250 TI - Controlling cephalosporin and aminoglycoside costs through pharmacy and therapeutics committee restrictions. AB - The cost-reducing effect of antibiotic restrictions imposed by a pharmacy and therapeutics (P & T) committee was evaluated. The pharmacy department developed guidelines restricting the use of second-generation cephalosporins and aminoglycosides in cooperation with the infectious disease division. The P & T committee approved the restrictions, and the pharmacy department disseminated information on the program to the hospital's physicians. Specific indications were developed for the use of amikacin, tobramycin, cefoxitin, and cefamandole. In order to prescribe a restricted antibiotic, physicians are required to write an approved indication on the physician's order form. Residents cannot prescribe restricted antibiotics for unapproved indications unless they acquire the signature of an attending physician. Pharmacy personnel closely monitor the restricted antibiotic use and enforce the established guidelines. The major impact of the restrictions was the reversal of a previous trend toward the use of more expensive second-generation cephalosporins and tobramycin to the use of first-generation cephalosporins and gentamicin. Injectable antibiotic expenses decreased by $193,172 in the first 12 months of the program. Antibiotic restrictions imposed by the P & T committee were effective in reducing the cost of antimicrobial therapy. PMID- 4014251 TI - Implementing clinical pharmacy services in an outpatient oncology clinic. AB - The implementation of clinical pharmacy services in an outpatient oncology clinic is described. An oncologist hired by the department of internal medicine and the director of the department of pharmacy designed the program. Both departments agreed that the pharmacists should have central responsibility for the antineoplastic agents. Pharmacists for the program were selected from the existing staff. They were trained in an established i.v. therapy certification course offered by the hospital. The biweekly clinics are staffed by a team consisting of two pharmacists, three nurses, two faculty physicians, and a rotating resident physician. The pharmacists provide clinical and distributive services including patient monitoring and medication storage, delivery, preparation, administration, and disposal. A survey showed that the pharmacists were well accepted by the other members of the team. After a trial period, principles of break-even analysis and differential accounting were used to justify the costs of the program. This program will remain an integral part of this hospital's pharmaceutical services. PMID- 4014252 TI - Compatibility of heparin sodium and morphine sulfate. AB - The compatibility of morphine sulfate and heparin sodium was studied in solutions of deionized water and 0.9% sodium chloride. Crystalline morphine sulfate was reconstituted and heparin sodium 100 or 200 units/mL was added. Duplicate samples with a final volume of 5 mL were prepared and stored at room temperature. Morphine sulfate concentrations were 1, 2, 5, and 10 mg/mL in each diluent with each heparin concentration. Samples were visually inspected immediately after preparation and at 0.5 and 24 hours; pH was tested before adding heparin and at 0.5 and 24 hours. Similar procedures were followed adding morphine to the heparin. Samples containing morphine sulfate 2 and 10 mg/mL were analyzed by high performance liquid chromatography for morphine concentrations immediately before adding heparin and at 0.5 and 24 hours. Precipitate appeared immediately after the second drug was added in samples containing morphine sulfate 10 mg/mL at both heparin concentrations in the water admixtures. No precipitate formed in any solutions containing morphine concentrations of 5 mg/mL or less nor in any samples containing 0.9% sodium chloride. In both diluents, pH values decreased as morphine sulfate concentrations increased. Morphine sulfate concentrations decreased significantly in water admixtures but not in admixtures prepared with 0.9% sodium chloride solution. Morphine sulfate and heparin sodium are incompatible only at morphine concentrations greater than 5 mg/mL. The incompatibility can be prevented by using 0.9% sodium chloride as the admixture diluent. PMID- 4014253 TI - Evaluation of an extension set for intermittent intravenous drug delivery to infants. AB - An intravenous administration set designed for delivery of drug doses to pediatric patients was tested in vitro for the effect of fluid density and flow rate on drug delivery, and delivery of drug by this extension set was compared in vivo with delivery by other methods. Gentamicin (as the sulfate salt) and penicillin G potassium were used to represent low-density and high-density drugs, respectively; a 1-mL solution of each drug, labeled with carbon 14, was tested with each of two primary infusion solutions: 0.45% sodium chloride injection and 10% dextrose injection. The drug dose was injected via a port into a piston containing chamber from which an equivalent amount of the primary fluid was displaced. Serial samples collected from the end of the filter-containing extension set were analyzed for drug concentration using a liquid scintillation technique. In 12 infants receiving i.v. gentamicin, this delivery method was compared in a randomized crossover trial with delivery by a syringe pump and by i.v. push. Each delivery system was used on one of three consecutive days, and serum gentamicin concentrations were measured by enzyme-multiplied immunoassay. The time required for in vitro delivery of the dose was dependent on flow rate. Density of the drug solution or the primary i.v. fluid did not significantly affect drug delivery. Serum gentamicin concentrations were not significantly different for the three delivery methods, but variability of drug delivery was greatest with the pediatric extension set. This pediatric extension set provides accurate and reliable drug delivery at primary infusion flow rates slower than 10 mL/hr when the drug dosage volume is 2-3 mL or less. PMID- 4014254 TI - Pharmacists' perceptions of mental health care, psychiatrists, and mentally ill patients. AB - The attitudes of hospital pharmacists in Texas toward mental health care, psychiatrists, and mentally ill patients were evaluated. The pretested survey instrument contained 33 statements, which the respondents graded on a five-step Likert scale. These questionnaires were mailed to a random sample of 300 pharmacists. In general, the 170 respondents perceived psychiatrists and mentally ill patients in a positive manner. The psychiatrist was viewed as a true professional with legitimate expertise, and mentally ill patients were considered to be basically similar to normal individuals, generally rational, nondangerous, and without blame for their disease. The pharmacists showed more negative attitudes toward hospitals for mentally ill patients. They supported statements that depicted mental hospitals as understaffed, too drug oriented, and at times insensitive to individual needs. The surveyed hospital pharmacists generally demonstrated healthy, unprejudiced views toward psychiatrists and mentally ill patients; however, their attitudes toward mental hospitals were skewed in the negative direction. PMID- 4014255 TI - Challenges in purchasing and inventory control. AB - In this concluding installment in a multipart series, issues that should be considered in the improvement of hospital pharmacy purchasing and inventory control systems are presented. Pharmacists must be aware of possible variation in bioavailability among different formulations of the same drug and evaluate new vendors critically. Hospital pharmacists and industry representatives should strive for a cooperative relationship by fostering ongoing dialogue. Pharmacists must continue to demand competitive bid prices on generically equivalent products of equal quality. Firm contact prices cannot be expected if product use estimates are unreliable. It is unethical to encourage additional price reductions on competitive products after a formal bid has been received. Institutions should limit their participation to one group purchasing organization or wholesaler for the competitive bid process. Inventory management through methods such as ABC analysis, economic-order quantities, calculated optimum reorder points, and other quantitative measurements should become commonplace. The use of data processing systems and devices can enable pharmacists to become more proficient at pharmaceutical purchasing and inventory control. The acquisition and distribution of pharmaceuticals in health-care institutions require good management to capture the opportunities in this area for pharmacy to contribute to fiscally sound health care. PMID- 4014256 TI - Gynecomastia in a hospitalized male population. PMID- 4014257 TI - Potential hazards of 67gallium lung scanning. PMID- 4014258 TI - Effects of a high-complex-carbohydrate, low-fat, low-cholesterol diet on levels of serum lipids and estradiol. PMID- 4014259 TI - Erythrocyte sedimentation rate. From folklore to facts. AB - The erythrocyte sedimentation rate is a simple, inexpensive laboratory test that clinicians have used for decision-making for over 50 years. Despite this fact, many criticize the test because of its lack of specificity and because the concept of erythrocyte sedimentation rate as a "sickness index" seems scientifically unsound. This review discusses the physical and chemical properties that govern red blood cell sedimentation, how sedimentation is measured, and the way in which the erythrocyte sedimentation rate has previously been used to assist in the diagnosis of infectious, inflammatory, or neoplastic disease. The clinical significance, sensitivity, specificity, and predictive value of a low or elevated erythrocyte sedimentation rate are also re-evaluated. PMID- 4014260 TI - Fever and abdominal mass in a 74-year-old man with long-standing vena caval obstruction. PMID- 4014261 TI - Metastatic intravagal paraganglioma. Case report and review of the literature. AB - Intravagal paragangliomas are rare tumors of neural crest origin. These tumors are usually benign with few reports of metastases or aggressive behavior. One case of intravagal paraganglioma metastatic to a regional lymph node is described and the diagnosis and management of these tumors are discussed. The reports of 14 other cases with regional or distal metastases are reviewed. PMID- 4014262 TI - Hypocalcemic heart failure. AB - Hypocalcemia is a relatively uncommon but reversible cause of congestive heart failure. A 39-year-old woman with hypocalcemia due to untreated hypoparathyroidism presented with congestive heart failure and a left ventricular ejection fraction of 25 percent. She had no evidence of underlying cardiac disease. The serum calcium level was normalized within one week, associated with complete clearing of the signs and symptoms of heart failure and a twofold increase to 50 percent in the ejection fraction. This is the first patient without underlying myocardial disease in whom significant improvement of left ventricular function has been quantitatively assessed prior to and following correction of hypocalcemia. PMID- 4014263 TI - Reversible decerebrate posturing secondary to hypoglycemia. AB - Two cases of decerebrate posturing that resolved following the administration of dextrose are reported. The literature on hypoglycemia-induced neurologic deficits is reviewed and an explanation for the quick remission of the decerebrate posturing is postulated. PMID- 4014264 TI - Neisseria sicca pneumonia. Report of two cases and review of the literature. AB - Neisseria sicca is considered part of the normal flora of the oropharynx. Although usually believed to be a harmless saprophyte, it has rarely been recognized as an etiologic agent in human disease, particularly in immunodeficient hosts. Two immunodeficient women are described in whom N. sicca pneumonia of the left lower lobe developed. One patient was 30 years old and had just completed a full-term pregnancy, and the other patient was 73 years of age and was receiving prednisone for bullous pemphigoid. Each had an uncomplicated pulmonary course, the pneumonia being successfully treated with penicillin or cephalothin. Only one patient with N. sicca pneumonia has been previously described in the literature. The significance of N. sicca pneumonia is discussed on the basis of a review of findings in these three patients. Although unusual N. sicca should be considered among the organisms causing pneumonia in immunodeficient patients. PMID- 4014265 TI - Neurogenic bladder. New clinical finding in Legionnaires' disease. AB - Legionnaires' disease presents with a spectrum of organ involvement including pulmonary, hepatic, gastrointestinal, metabolic, and renal dysfunction. Known neurologic manifestations include hallucinations, delirium, cerebral and cerebellar disturbance, and encephalomyelitis. Clinical and subclinical peripheral neuropathy has been described. This report describes a 51-year-old man with legionnaires' disease complicated by cerebral and persistent cerebellar and brainstem dysfunction, without evidence of direct bacterial invasion of the nervous system. Of particular interest was the development of a flaccid neurogenic bladder, a clinical manifestation not previously described. PMID- 4014266 TI - Changing concepts in treatment of severe symptomatic hyponatremia. Rapid correction and possible relation to central pontine myelinolysis. AB - Severe symptomatic hyponatremia (serum sodium level below 120 meq/liter) is often a life-threatening emergency that can result in permanent neurologic damage or death if left untreated. Early recognition and rapid correction to mildly hyponatremic levels by the administration of hypertonic saline are important in order to reduce the potential mortality and morbidity. If the serum sodium level is more than 105 meq/liter, it can be corrected to a value of 125 to 130 meq/liter. However, if the serum sodium level is less than 105 meq/liter, it may be safe to raise the value by only 20 meq/liter. Care should be taken to avoid acute correction to normonatremia or hypernatremia. Moreover, it is also of equal importance to avoid development of hypernatremia in the subsequent days following the correction to mild hyponatremia. PMID- 4014267 TI - Two-dimensional echocardiographic detection of preclinical aortic root abnormalities in rheumatoid variant diseases. AB - Two-dimensional echocardiographic findings of subaortic fibrous ridging, aortic leaflet thickening, and aortic root dilatation and thickening are described in a group of 36 patients with rheumatoid variant diseases. The group consisted of 25 patients with ankylosing spondylitis, nine patients with Reiter's syndrome, and two patients with inflammatory bowel disease and spondylitis. No patient had clinical or laboratory evidence of aortic regurgitation or heart block. Subaortic fibrous ridging or marked leaflet thickening was noted in 11 of 36 patients; in contrast, no such changes were found in an age-matched control group of 29 men. The subgroup of patients with subaortic fibrous ridging or leaflet thickening (11 patients) had significantly longer disease duration (28.1 versus 17.7 years) and higher incidence of aortic root echo-density (82 versus 36 percent) than the remaining patients. It is concluded that a significant portion of patients with ankylosing spondylitis or Reiter's syndrome have echocardiographic evidence of aortic root involvement prior to the clinical onset of aortic regurgitation. PMID- 4014268 TI - "Noninvasive" oral treatment of asthma in the emergency room. AB - One hundred forty consecutive patients with acute asthmatic episodes presenting to the emergency room were studied prospectively to assess the efficacy of oral therapy. After the emergency room staff was oriented to the pharmacologic action of hydroalcoholic elixir of theophylline, oral terbutaline, and a metered-dose hand-held nebulizer (metaproterenol), use of oral therapy as initial therapy rose from 12 percent to 76 percent (p = 0.005). More than half of these patients were discharged without receiving any of the traditional more invasive therapies of subcutaneous epinephrine, intravenous hydrating fluids with aminophylline, and machine-delivered sympathomimetic aerosols. Oral therapy did not substantially alter the total time spent in the emergency room. Only 4 percent treated with oral therapy required further treatment in the emergency room within 48 hours; 2 percent vomited after treatment. Oral therapy is safe and effective for most asthmatic patients presenting to the emergency room, as they generally are undermedicated with regard to theophyllines and sympathomimetic drugs. Use of oral therapy in the emergency room is a potent tool for educating asthmatic patients in the use of medication available for home use. The patients who require emergency room treatment despite being well-medicated at home (a small minority) need a higher level of care including intermittent positive-pressure breathing, corticosteroids, and often hospitalization. PMID- 4014269 TI - Effect of labetalol on exercise tolerance and double product in mild to moderate essential hypertension. AB - Maximal exercise capacity after control of resting blood pressure with labetalol was studied in nine hypertensive men aged 34 to 69 years (average 52 years). Subjects exercised to exhaustion on an upright cycle ergometer with workload increased as a step function by 25 watts every three minutes, both before and after control of blood pressure was obtained. Mean exercise capacity expressed as total time of exercise until exhaustion was 936 seconds prior to control of the resting blood pressure and 884 seconds (no significant difference) after control of resting blood pressure with labetalol. Double product at peak exercise fell from 254 X 10(2) mm Hg beats per minute prior to blood pressure control to 183 X 10(2) mm Hg beats per minute (p = 0.006) after control of blood pressure with labetalol. The difference in the means of resting heart rate and both peak blood pressure and peak heart rate with exercise were all statistically significant after control of blood pressure with labetalol. These findings suggest that labetalol has an ideal exercise profile affording a cardioprotective effect by decreasing double product but without sacrificing exercise capacity. PMID- 4014270 TI - Risk factors for the development and rupture of intracranial berry aneurysms. AB - Risk factors for the development and rupture of intracranial saccular (berry) aneurysms were identified in a case-control study of autopsy subjects. The development of berry aneurysms was positively correlated with increased frequencies of systemic arterial hypertension (p less than 0.001), cerebral artery atherosclerosis (p less than 0.05), and marked asymmetry of the cerebral vessels comprising the circle of Willis (p less than 0.005). In addition, patients with berry aneurysms more frequently had histories of persistent headache (p less than 0.001), pregnancy-induced hypertension (p less than 0.01), long-term use of analgesics (p less than 0.001), especially aspirin (p less than 0.05), and a family history of stroke (p less than 0.05). Factors associated with a decreased risk of berry aneurysms included treatment with insulin to control diabetes mellitus (p less than 0.005), leanness (p less than 0.05), chronic pancreatitis (p less than 0.001), malignant tumors (p less than 0.001), and moderate or severe coronary or renal atherosclerosis (p less than 0.05). Rupture of berry aneurysms was positively correlated with size (p less than 0.05) and the presence of multiple aneurysms (p less than 0.005), but also with long-term analgesic usage (p less than 0.05), excessive ethanol consumption (p less than 0.01), and fatty metamorphosis of the liver (p less than 0.01). The factors that predispose to rupture of berry aneurysms are interrelated in the sense that several of them are known to cause a decrease in the synthesis of prostaglandin E, whereas one of the factors that appears to be protective has the opposite effect. Marked and abrupt lowering of serum prostaglandin levels would cause dilatation of cerebral vasculature and increased cerebral blood flow; in the setting of hypertension, focal defects in cerebral arteries could develop, leading to the formation and subsequent rupture of berry aneurysms. PMID- 4014271 TI - Meningitis due to Staphylococcus aureus. AB - A retrospective analysis of 10 adult patients with community-acquired Staphylococcus aureus meningitis was performed in order to elucidate the characteristics and treatment of this lethal disease. In all patients, a focus of infection outside the central nervous system was apparent at presentation. A poor prognosis was associated with severe underlying disease, greater degree of hyponatremia at presentation, development of seizures, failure of nuchal rigidity to develop, persistent or recurrent bacteremia, and the presence of concurrent S. aureus bronchopneumonia. Degree of deterioration in mental status and cerebrospinal fluid pleocytosis, protein levels, and glucose levels did not appear to have any prognostic significance. Therapy with rifampin and a semisynthetic penicillin effected a cure in all six patients treated with this regimen. In contrast, three of four patients treated with other antibiotic combinations died. On the basis of this experience, it is concluded that further trials with rifampin in combination with another anti-staphylococcal antibiotic for the treatment of S. aureus meningitis are warranted. PMID- 4014272 TI - Complement-activating antineutrophil antibody in systemic lupus erythematosus. AB - Serum samples from 18 patients with systemic lupus erythematosus (SLE) were tested for neutrophil C3-fixing ability and neutrophil-binding lgG by the binding of radioiodinated monoclonal anti-C3 antibody and staphylococcal protein A to paraformaldehyde-fixed allogeneic neutrophils sensitized with serum. Serum from patients with SLE resulted in the binding of significantly greater amounts of lgG to neutrophils than normal serum, but this lgG binding did not correlate with the degree of neutropenia. In contrast, serum samples from 10 neutropenic patients with SLE resulted in the binding of significantly greater amounts of C3 to neutrophils when compared with serum samples from eight non-neutropenic patients with SLE. Fixation of C3 to neutrophils by serum from patients with SLE appeared to be due to the binding of complement-activating monomeric antineutrophil lgG autoantibody. A significant negative correlation (r = -0.78) between the neutrophil count and the C3-fixing ability of serum from patients with SLE suggested that antineutrophil antibody-mediated activation of complement may be important in the pathophysiology of neutropenia in SLE. PMID- 4014273 TI - Influence of medical and premedical education on important personal qualities of physicians. AB - Three interrelated personal qualities of physicians are believed important for sensitive patient care and optimal individual adjustment to the stresses of medical practice: maturity, social competence, and moderation in aggressive competitive (exaggerated "type A" behavior). Despite widespread recognition of the importance of these qualities by patients and physicians alike, they have commonly been neglected in favor of scientific and scholastic excellence in the selection process for medical schools. In addition, some aspects of premedical and medical education may actually have an adverse influence on these personal qualities of future physicians. More emphasis in premedical and medical education on the importance of physicians' noncognitive abilities, and more individualized feedback to students and residents on the interactions between their personal qualities and their success and happiness as physicians, are needed. PMID- 4014275 TI - Infective endocarditis. An overview. PMID- 4014274 TI - Emerging perspectives in management and prevention of infectious diseases. PMID- 4014276 TI - Pathogenesis of endocarditis. AB - The pathophysiology of infective endocarditis comprises at least three critical elements: preparation of the cardiac valve for bacterial adherence, adhesion of circulating bacteria to the prepared valvular surface, and survival of the adherent bacteria on the surface, with propagation of the infected vegetation. It appears that circulating bacteria do not readily adhere to normal endothelial surfaces. Trauma to the valve, however, produces an alteration in the endothelial cells, leading to either disruption of the surface and deposition of platelets and fibrin, or other phenomena that render the surface susceptible to colonization by circulating bacteria. Once the surface is prepared, some bacterial strains appear to adhere to the fibrin-platelet matrix more avidly than others. The bacterial virulence factors that promote adherence are complex, but at least one, an extracellular polysaccharide (dextran), has been identified. Adherence can be blocked by antibodies directed against various surface structures. The survival of bacteria adherent to the surface of the vegetation appears to be complex as well, requiring resistance in situ to the bactericidal properties of complement and phagocytosis by white cells. In addition, vegetation propagation involves activation of the clotting cascade. For at least some streptococci, this occurs partly through perturbation of the valvular cells to produce tissue factor (tissue thromboplastin), which results in the deposition and growth of a fibrin-platelet clot over the rapidly growing bacterial colonies. PMID- 4014277 TI - Current issues in prevention of infective endocarditis. AB - Prevention of infective endocarditis continues to concern health care providers in many specialties. The well-known lack of primary clinical trials in this area is not expected to change. Therefore, the evolution of recommendations and practice must be based on theoretic considerations and continuing assessment of secondary sources of information. Recent developments include a report of 52 cases in which antibiotic prophylaxis for infective endocarditis was attempted but appeared to fail. Most of these patients had undergone dental procedures after oral penicillin prophylaxis, with subsequent development of streptococcal endocarditis. In two thirds, the organism was sensitive to the antibiotic used. Notably, the most common underlying cardiac lesion among these patients was mitral valve prolapse. However, two recent independent analyses have concluded that providing endocarditis prophylaxis for all patients with mitral valve prolapse during procedures that might cause bacteremia would not be cost effective. This is primarily because mitral valve prolapse is common and endocarditis is relatively rare, resulting in an adverse risk-benefit ratio. Parenteral prophylaxis for mitral valve prolapse might even cause a net loss of life from anaphylaxis. On the other hand, for the individual patient or physician, the reassurance provided by attempted prophylaxis with oral penicillin can be purchased at low cost and low risk. Very few cases of infective endocarditis have been reported after gastrointestinal and other endoscopic procedures; most of these do not need antibiotic coverage. Prophylactic antibiotics should be restricted to those situations in which both the procedure and the underlying cardiac condition seem to pose significant risk, for example, endoscopic sclerotherapy of esophageal varices in patients with prosthetic heart valves. Newly revised recommendations have been issued by the Medical Letter, the American Heart Association, and the American Dental Association. These regimens are shorter and simpler than earlier versions. PMID- 4014278 TI - Changing pattern of infective endocarditis. AB - There has been a significant trend toward an increase in the age of patients with endocarditis, and it seems likely that the age of these patients will continue to increase as the population ages. The proportion of patients with endocarditis who have rheumatic heart disease as an underlying lesion has decreased from about 40 percent in patients studied from 1950 to 1970 to about 25 percent in more recent series, and this trend will probably continue. Prosthetic valves and degenerative heart disease will undoubtedly become increasingly important underlying heart lesions in patients with endocarditis. Another large group of patients with infective endocarditis have no diagnosable underlying heart disease and comprise an increasing proportion of patients with endocarditis. Because of the aging of the population, more Streptococcus bovis and enterococcal endocarditis should be expected. With more prosthetic valves and with the aging of the population, more staphylococcal endocarditis should be anticipated. Economic forces will probably result in earlier discharge from the hospital, with either shorter courses of therapy or completion of therapy at home and perhaps more valve replacements. PMID- 4014279 TI - Obstetrics and gynecology. An overview. PMID- 4014280 TI - Patient cost in the treatment of postsurgical female pelvic infection. AB - Soft tissue female pelvic infections, that is, postpartum endomyometritis, pelvic cellulitis, and salpingitis, are frequently polymicrobial, involving aerobic and anaerobic bacteria. The most common antibiotic regimen employed for the treatment of these patients is clindamycin and an aminoglycoside. Single-agent therapy, utilizing the newer beta-lactams, is more economical, potentially less toxic, and as effective. PMID- 4014281 TI - Bone and joint infections. An overview. PMID- 4014282 TI - Animal models of osteomyelitis. AB - Clinical research involving osteomyelitis is difficult because of the multiple variables found in the disease process. In order to evaluate osteomyelitis critically, a more precise staging system is needed, along with reproducible animal models for each of the clinical stages. The current animal models for osteomyelitis include the rabbit models of Norden and Andriole, the rat model of Zak, and the dog models of Fitzgerald and Deysine. Although each animal model of osteomyelitis has certain advantages and limitations, they have provided us with a clearer understanding of this disease process and what forms of treatment may prove satisfactory. PMID- 4014283 TI - Hip implant infection. Treatment with resection arthroplasty and late total hip arthroplasty. AB - In 131 patients with an infected hip implant, treatment was surgical excision of the implant (resection arthroplasty) and delayed reconstruction with a total hip arthroplasty. Most of the patients had low-grade infections: only 5 percent had a temperature of 37.8 degrees C or higher and only 20 percent had wound drainage. Hip pain was the primary symptom of a deep infection in 90 percent. Staphylococci were the most frequently isolated causal organisms, recovered from deep tissue specimens in 84 patients. The hip was reconstructed six days to 32 years (mode, 429 days) after resection arthroplasty. At follow-up two to nine years after reconstruction, 88 percent of the 131 patients were free of infection. Recurrent sepsis was more common (p less than 0.05) in patients with incomplete acrylic cement removal or patients in whom reconstruction was performed less than 429 days after resection arthroplasty. Risk of recurrent sepsis was increased when gram-negative bacilli in pure or mixed cultures were found, but the difference was not statistically significant. PMID- 4014284 TI - Emerging perspectives in management and prevention of respiratory tract infections. An overview. PMID- 4014285 TI - Epidemiology of community-acquired respiratory tract infections in adults. Incidence, etiology, and impact. AB - Upper respiratory tract infections are the most common types of infectious diseases among adults. It is estimated that each adult in the United States experiences two to four respiratory infections annually. The morbidity of these infections is measured by an estimated 75 million physician visits per year, almost 150 million days lost from work, and more than $10 billion in costs for medical care. Serotypes of the rhinoviruses account for 20 to 30 percent of episodes of the common cold. However, the specific causes of most upper respiratory infections are undefined. Pneumonia remains an important cause of morbidity and mortality for nonhospitalized adults despite the widespread use of effective antimicrobial agents. There are no accurate figures on the number of episodes of pneumonia that occur each year in ambulatory patients. In younger adults, the atypical pneumonia syndrome is the most common clinical presentation; Mycoplasma pneumoniae is the most frequently identified causative agent. Other less common agents include Legionella pneumophila, influenza viruses, adenoviruses, and Chlamydia. More than half a million adults are hospitalized each year with pneumonia. Persons older than 65 years of age have the highest rate of pneumonia admissions, 11.5 per 1,000 population. Pneumonia ranks as the sixth leading cause of death in the United States. The pathogens responsible for community-acquired pneumonias are changing. Forty years ago, Streptococcus pneumoniae accounted for the majority of infections. Today, a broad array of community-acquired pathogens have been implicated as etiologic agents including Legionella species, gram-negative bacilli, Hemophilus influenzae, Staphylococcus aureus and nonbacterial pathogens. Given the diversity of pathogenic agents, it has become imperative for clinicians to establish a specific etiologic diagnosis before initiating therapy or to consider the diagnostic possibilities and treat with antimicrobial agents that are effective against the most likely pathogens. PMID- 4014286 TI - Emerging perspectives in management and prevention of infections of the respiratory tract in infants and children. AB - New products, new procedures, new information, and new legislation will have a significant impact on management and prevention of respiratory infections in children. Current areas of investigation include the changing epidemiology (increased number of children in day care), concern about morbidity of common infections (hearing impairment and effect on development of speech and language due to otitis media), and new modes of microbiologic diagnosis (antigen detection). New antimicrobial agents have wider spectrums of activity, increased concentrations in body fluids, and lesser toxicity than available drugs. New uses of old drugs are identified (value of erythromycin for Legionella pneumophila, Chlamydia trachomatis, and Mycoplasma pneumoniae). Increased usage of chemoprophylaxis for prevention of recurrences of acute otitis media follows publication of impressive results of recent studies. New conjugate polysaccharide vaccines are immunogenic in young infants. Finally, and of major importance to children, physicians, and manufacturers, is vaccine liability legislation, now in congressional committee. PMID- 4014287 TI - Economic costs of respiratory tract infections in the United States. AB - To evaluate one aspect of the impact of respiratory tract infections in the United States, national survey data were used to estimate direct and indirect economic costs. Overall, upper and lower respiratory tract infections are estimated to be responsible for approximately $15 billion in direct treatment costs. Physician charges account for about one half and hospital care accounts for approximately one quarter of these costs. An estimated 1.25 million patients are hospitalized yearly for community-acquired respiratory tract infections, and charges for their care are projected to exceed $4 billion. Almost 300 thousand patients acquire nosocomial respiratory infections yearly, and charges for treating these infections are approximately $470 million. Although costs associated with hospital care are substantial, approximately $10 billion (67 percent of the total estimated cost of these infections) results from treatment of patients in ambulatory settings. It is not possible to calculate the full magnitude of the indirect costs of respiratory infections, but losses in income of employed persons who miss work because of infection are calculated to be more than $9 billion per year. PMID- 4014288 TI - Community-acquired lower respiratory tract infections. Prevention and cost control strategies. AB - The treatment of patients with community-acquired pneumonia can be expensive, particularly if care is hospital-based. Cost control begins with prevention. Current influenza vaccines are about 80 percent protective, but grossly underused. Amantadine and rimantadine are effective chemoprophylactic agents against influenza A, but also underused. Use of pneumococcal vaccine is controversial, but patients who are thought to be at increased risk should be immunized. Management decisions in patients with pneumonia that have major cost implications include the need for hospitalization and choice of diagnostic tests and therapy. The need for hospitalization has not been well studied. In general, young patients with atypical pneumonia are treated at home, whereas older patients with complicating illnesses are admitted to hospitals. Length of hospitalization has decreased in recent years. Diagnostic tests have traditionally emphasized chest roentgenography, Gram staining of the sputum, and sputum culture. Published data suggest that a Gram staining of the sputum can be useful. Sputum cultures are frequently confusing and should be discontinued. Intermittent positive pressure breathing treatments have no value, and chest physiotherapy is unnecessary for most patients. PMID- 4014289 TI - Respiratory tract infections. Goals for 1995. AB - Goals to be identified for 1995, a decade hence, in the prevention, diagnosis, and management of respiratory tract infections may conveniently be divided into diagnostic goals and goals in therapy and prophylaxis. Major diagnostic goals for bacterial, viral, and mycoplasmal infections of the respiratory tract focus on the development of systems to identify microbial components, such as specific antigens or segments of DNA, using monoclonal antibody techniques or DNA probes for hybridization. Sputum cultures, in the traditional sense, should ultimately become obsolete. Management goals include the development of algorithms to identify patients who should be hospitalized, in contrast to those who can safely be treated on an outpatient basis. New antibiotic drug development should include drugs active against methicillin-resistant staphylococci, broad-spectrum beta lactam drugs that are orally active against gram-negative bacilli, and drugs that can be used parenterally on a once-daily basis in settings other than the acute care hospital. There are certainly needs to enhance the present spectrum of antiviral drugs and to develop therapeutically useful immunomodulators. There are promising prospects for vaccine development, including live attenuated influenza virus vaccine, parainfluenza virus vaccine, respiratory syncytial virus vaccine, and a Mycoplasma pneumoniae vaccine. With major research support, such vaccines could possibly be fully developed by 1995. Finally, of greatest importance is the need to achieve greater utilization of existing vaccines, that is, inactivated influenza vaccine and the current 23-valent pneumococcal vaccine. A legitimate goal for 1995 would be to achieve 70 percent or greater utilization of these vaccines within the recommended target populations. PMID- 4014290 TI - Diarrheal diseases. An overview. PMID- 4014291 TI - Evaluation and diagnosis of acute infectious diarrhea. AB - The appropriate approach to the diagnosis and management of acute infectious diarrhea is determined by the frequency and setting of the illness, the recognizable causes or syndromes, the cost and yield of available diagnostic tests, and the treatability of the disease. Acute diarrhea affects everyone throughout the world from one to more than six times each year, depending on age, location, and living conditions. The range of identifiable viral, bacterial, and parasitic etiologies is great, and the cost of indiscriminate use of etiologic studies for diagnosis is prohibitive. Because of its insensitivity for many organisms and poor selection of cases for testing, routine stool culture has been one of the most costly and ineffective microbiologic tests; the cost per positive result has traditionally exceeded $900 to $1,000. The appropriate treatment for the vast majority of cases (independent of their cause) is simple and effective: oral glucose- and electrolyte-containing rehydration solution. On the basis of an appropriate history and understanding of pathogenesis, fecal specimens can be selectively obtained and promptly examined for leukocytes and parasites, and the common noninflammatory diarrheas can be separated from the inflammatory infections in order to focus further studies on the latter group. The bacteria for which specific antimicrobial therapy should be considered usually cause inflammatory diarrhea in the United States. Therefore, only when the history or fecal leukocyte findings indicates an inflammatory process is it appropriate to culture for the routine invasive bacterial pathogens. In sporadic inflammatory diarrhea, culture methods should include those for Campylobacter jejuni as well as Salmonella and Shigella. Several special circumstances may prompt a consideration of parasites (including Giardia, Entamoeba, Strongyloides, Cryptosporidium), Vibrio, Yersinia, Clostridium difficile, enterotoxigenic Escherichia coli, food-borne agents, or sexually transmitted pathogens. The practical value of specific identification of rotaviruses (by enzyme-linked immunosorbent assay, Rotazyme, or electron microscopy) is primarily epidemiologic, particularly in hospitalized infants or young children. Using such a selective approach to fecal culture will greatly increase its yield and can reduce the cost per positive result from $1,000 to less than $150. PMID- 4014292 TI - Pure primary hyperaldosteronism due to adrenal cortical carcinoma. PMID- 4014293 TI - Catheter-induced versus spontaneous spasm. Do these coronary bedfellows deserve to be estranged? PMID- 4014294 TI - Guillain-Barre syndrome following danazol and corticosteroid therapy for hereditary angioedema. AB - A case of hereditary angioedema secondary to C1 esterase inhibitor deficiency associated with lupus-like nephritis is reported. The patient was initially treated with both corticosteroids and danazol and subsequently had Guillain-Barre syndrome together with appearance of circulating immune complexes and an increase in total complement and C1q, C3, C4, B, and C1 esterase inhibitor levels. Guillain-Barre syndrome might be secondary to danazol therapy since this drug could increase both circulating immune complex production and complement synthesis, thereby providing additional substrate for the underlying immune complex disease. Normalization of complement might therefore be hazardous in lupus with underlying complement deficiency states. PMID- 4014295 TI - Exogenous protein as the cause of nephrotic-range proteinuria. AB - Hematuria and proteinuria developed in a young woman with waxing and waning symptoms suggestive of systemic lupus erythematosus. Quantitatively, the proteinuria was in the nephrotic range, but other manifestations of the nephrotic syndrome were absent. Serologic evaluation demonstrated normal results. The hematuria was subsequently found to be self-induced and related to foreign objects in the bladder. Urine protein electrophoresis confirmed severe proteinuria with a spike in the gamma region. Immunoelectrophoresis demonstrated that the proteinuria was not of human origin. Subsequent urinary protein values were normal. This case exhibits features compatible with Munchausen's syndrome and shows that severe proteinuria may be factitious. PMID- 4014296 TI - Development of malignant melanoma after levodopa therapy for Parkinson's disease. Report of a case and review of the literature. AB - Malignant melanoma developed in an apparently benign nevus four months after therapy with levodopa in a patient with Parkinson's disease. This case is reported, and previous reports of this possible causal relationship are reviewed. Although this and previously reported cases are not inconsistent with the unpredictable and variable natural history of malignant melanoma, it seems prudent to clinically monitor pigmentary lesions in patients receiving levodopa therapy. Biopsy specimens of suspicious lesions in these patients should be examined histologically, and if malignancy is found, alternate therapies for treatment of parkinsonism should be considered. PMID- 4014297 TI - Novel factor X deficiency. Normal partial thromboplastin time and associated spindle cell thymoma. AB - This report presents a heretofore undescribed laboratory variant of congenital factor X deficiency, seen in conjunction with a relatively rare tumor. The patient had a history of bleeding, a prolonged prothrombin time, and a factor X value of 4.2 percent of normal activity, but the partial thromboplastin time and Russell's viper venom clotting time were normal. Management of this case required unusual measures to treat the patient's coagulopathy. PMID- 4014298 TI - Pseudohyperparathyroidism. Syndrome associated with aluminum intoxication in patients with renal failure. AB - Aluminum intoxication is an increasingly frequent complication of chronic renal failure. Because hypercalcemia, elevated parathyroid hormone levels, and radiologic changes said to be typical of osteitis fibrosa commonly occur with aluminum intoxication, it is frequently confused with hyperparathyroidism. In this report, examples of this dilemma are described. The pathophysiology leading to the confusing clinical picture is discussed, with a suggested approach to the problem. PMID- 4014299 TI - Evaluation of hyperviscosity in monoclonal gammopathies. AB - The serum or plasma hyperviscosity syndrome has been described in both monoclonal and polyclonal immunoglobulin disorders. The usefulness of initial and serial plasma viscosity measurements by an automated viscometer technique was evaluated and compared with serum protein electrophoresis data in 107 patients without monoclonal gammopathies and 153 patients with monoclonal gammopathies. In patients without monoclonal gammopathies, plasma viscosity correlated best with the concentration of gamma globulins. In patients with monoclonal gammopathies, plasma viscosity correlated best with the serum monoclonal protein concentration, but individual patient variations in the ratio of plasma viscosity to monoclonal protein concentration made accurate prediction of plasma viscosity difficult without direct measurement. Six of eight patients with plasma viscosity above 5.0 cp had classic symptoms of hyperviscosity syndrome, and four of the six had recurrent episodes. Six other patients with plasma viscosity above 4.0 cp had more subtle presentations of hyperviscosity but responded equally well to therapeutic lowering of plasma viscosity. These patients are part of a larger subset of 27 patients in whom initial plasma viscosity was above 3.0 cp. No patient with an initial plasma viscosity below 3.0 cp subsequently showed hyperviscosity symptoms. Plasma viscosity measured by this technique is a useful tool in screening patients with dysproteinemias to identify and monitor those with and at risk for the hyperviscosity syndrome. PMID- 4014300 TI - Autoinoculation herpes of the hand in a child with recurrent herpes labialis. AB - Herpes simplex virus infections involving the fingers and hands have been reported primarily in medical and dental personnel. A 10-year-old boy is described who presented with herpes simplex virus infection of his left hand two weeks after resolution of an episode of recurrent herpes labialis. Since herpes simplex infections of the fingers and hands may be confused with a variety of other more common conditions, clinicians should be alert to this possibility when diagnosing vesiculopustular lesions of the hands, particularly in medical and dental personnel and in patients with histories of recurrent herpes simplex infections elsewhere. A need for greater patient awareness of the potential for herpes simplex virus autoinoculation is also stressed. PMID- 4014301 TI - Insulin-induced cardiac failure. AB - Self-limited edema is a well-recognized complication of insulin therapy. However, progression to overt cardiac failure has only recently been reported in one patient with pre-existing heart disease. This report describes the first case of insulin-induced cardiac failure in a patient without underlying heart disease. Current trends toward intensive insulin therapy for rapid near-normalization of blood glucose levels will increase the recognition of this entity. Careful follow up of so-called "self-limited" insulin edema is encouraged, and the early institution of diuretic therapy is advocated in elderly patients to prevent the development of overt cardiac failure. PMID- 4014302 TI - Pulmonary functional impairment and symptoms in women in the Los Angeles Harbor area. AB - Spirometric measurements of vital capacity and flow rates, thoracic gas volume, and single-breath diffusing capacity for carbon monoxide were obtained in 360 white women, 238 wives age 58 years and 122 daughters age 32 years of shipyard workers from the Long Beach area of southern California. The values for nonsmokers, exsmokers, and current smokers were compared with smoking-specific mean values, age- and height-adjusted, from a reference population in Michigan. The wives from Long Beach had significantly lower mid and terminal flows, single breath diffusing capacity for carbon monoxide, and alveolar volume, except that single-breath diffusing capacity for carbon monoxide was not significantly lower in current smokers. Nonsmokers and ex-smokers showed significantly different values for one-second forced expiratory volume in addition to flow rates and single-breath diffusing capacity for carbon monoxide. Daughters showed significant reductions in single-breath diffusing capacity for carbon monoxide and alveolar volume, which are attributable to maldistribution of inspired gas. These data showed that a powerful factor has affected expiratory air flow and distribution of gas, resulting in altered single-breath diffusing capacity for carbon monoxide and alveolar volume in this population. The factor is additive with and resembles the effect of cigarette smoking, and it is postulated that this factor is oxidant air pollution. PMID- 4014303 TI - Mycobacterial meningitis. Retrospective analysis from 1970 to 1983. AB - The clinical presentation and course of tuberculous meningitis in 21 patients treated between 1970 and 1983 are analyzed. Tuberculous meningitis may present as acute, subacute, or chronic meningitis. Although characteristic cerebrospinal fluid findings of lymphocytic pleocytosis, low glucose level, and elevated protein level occur in the majority of cases, there are many atypical presentations. The protein level, glucose level, and white blood cell count may be normal, and there may be a predominance of polymorphonuclear cells rather than lymphocytes in the cerebrospinal fluid. Poor prognostic factors in this series were age greater than 65, underlying diseases, and stage 3 presentation. Incorrect or inadequate therapy had a disastrous outcome. Nontuberculous mycobacteria rarely are involved in central nervous system disease. Tuberculous meningitis must be considered in the differential diagnosis of any patient with fever and change in sensorium. A deteriorating mental status and falling cerebrospinal fluid glucose level in the presence of negative findings on bacterial culture and india ink preparation should lead to strong consideration for empiric initiation of anti-tuberculous therapy. PMID- 4014304 TI - Nocturnal oxyhemoglobin desaturation following tracheostomy for obstructive sleep apnea. AB - Eleven obese men with coexistent obstructive sleep apnea and chronic obstructive pulmonary disease underwent tracheostomy. Nocturnal polysomnography prior to tracheostomy revealed oxyhemoglobin desaturation associated with obstructive apnea. Following surgery, repeated polysomnography was performed to assess the effect of tracheostomy on nocturnal oxygen saturation. Non-apneic desaturation characteristic of that previously described in patients with "type B" chronic obstructive pulmonary disease was noted in six subjects. Oxyhemoglobin saturation in these six fell more than 8 percent below baseline waking and non-rapid-eye movement (REM) sleep levels. These episodes usually lasted five minutes or longer, occurred almost uniformly during REM sleep, and were acutely ameliorated by low-flow (4 liters per minute) supplemental oxygen. The subjects with REM associated desaturation did not differ from the subjects without desaturation by preoperative anthropomorphic, blood gas, or pulmonary function criteria. However, subjects with REM-associated desaturation tended to have lower right and left ventricular ejection fractions by pooled gated wall studies. It is concluded that patients with obstructive sleep apnea and chronic obstructive pulmonary disease should be re-evaluated after tracheostomy, since they may be at risk for continued oxyhemoglobin desaturation and progressive right ventricular deterioration despite adequate treatment of their apneic condition. PMID- 4014305 TI - Discriminant scorecard for diagnosis of invasive pulmonary aspergillosis in patients with acute leukemia. AB - Invasive pulmonary aspergillosis, a serious opportunistic infection in adult patients with acute leukemia, is difficult to diagnose antemortem. To identify patients with invasive pulmonary aspergillosis without reliance on invasive diagnostic procedures, a discriminant scorecard for invasive pulmonary aspergillosis based on clinical parameters was evaluated in a three-phase study. In phase I, the records of 62 patients, including 15 with invasive pulmonary aspergillosis, were reviewed. Eleven clinical parameters distinguished patients with invasive pulmonary aspergillosis from control subjects. These parameters were combined into a discriminant scorecard. In phase II, the discriminant scorecard was validated by a blinded, retrospective review of 94 consecutive admissions. The discriminant scorecard score was highly associated with the clinical outcome (p less than 0.0005). The sensitivity of the discriminant scorecard was calculated as a range from 62.9 to 92.8 percent and the specificity as a range from 87.5 to 98.3 percent. In phase III, the clinical utility of the discriminant scorecard was determined by its prospective application to 49 consecutive patient admissions. The discriminant scorecard identified patients with invasive pulmonary aspergillosis at an average of 4.1 days prior to clinical recognition of the disease and initiation of amphotericin B therapy. The discriminant scorecard outperformed a complex function based on multiple linear regressions, was easy to use, and did not require difficult calculations. Thus, for this patient population, the discriminant scorecard was an accurate, useful noninvasive screening test for invasive pulmonary aspergillosis. The scorecard allows more rapid clinical identification of patients with this infection and could lead to improved patient survival through earlier diagnostic and therapeutic intervention. PMID- 4014306 TI - Mouth and genital ulcers with inflamed cartilage: MAGIC syndrome. Five patients with features of relapsing polychondritis and Behcet's disease. AB - Five patients with features of coexistent relapsing polychondritis and Behcet's disease are described. Review of the literature supports the overlap of the clinical manifestations of these two conditions. A common immunologic abnormality is likely, and elastin is cited as a possible target antigen. The "mouth and genital ulcers with inflamed cartilage (MAGIC) syndrome" is the proposed name for this entity. PMID- 4014307 TI - Esophageal manometry in familial amyloid polyneuropathy. AB - The motility of the esophagus was studied by esophageal manometry in eight patients with familial amyloid polyneuropathy. All eight patients had an abnormality of the lower esophageal sphincter. Seven of eight had a borderline or decreased lower esophageal sphincter pressure and the other patient had a non relaxing lower esophageal sphincter pressure. Six of eight patients had abnormalities of the body of the esophagus consisting of either simultaneous or decreased amplitude of contractions involving the smooth or striated muscle or both. In addition, seven of eight patients had diarrhea and six of these seven patients had evidence for steatorrhea. The manometric abnormalities observed were consistent with deposition of amyloid in smooth and striated muscle as well as in the enteric nervous system. Esophageal manometry appears to be a sensitive technique to determine if the gastrointestinal tract is involved in familial amyloid polyneuropathy. PMID- 4014308 TI - Survival analysis of the severely and profoundly mentally retarded. AB - Life-table analyses were performed on 1,915 severely/profoundly retarded institutionalized persons. Data on probability of death and hazard rates are presented according to sex and previously described diagnostic/etiologic categories. The median remaining lifetime for a resident of Central Wisconsin Center on admission was found to be greater than 25 years. The average age of admission was 7.3 years with a range of 0-66 years. The highest death rate was noted in residents with inborn errors of metabolism; the lowest death rate was in residents with primary seizures disorders. On admission, the median remaining lifetime was 8.81 +/- 4.16 years (95% confidence interval) for residents with inborn errors of metabolism, 18.56 +/- 4.26 years for residents with primary CNS malformations, and 24.66 +/- 4.05 years for residents with known syndromes. Residents of all other diagnostic/etiologic categories had a median remaining lifetime of greater than 25 years. PMID- 4014309 TI - Partial deletion of distal 17q. AB - A newborn female was found to have a deletion of the terminal portion of 17q. Prominent manifestations included microcephaly, apparent hypertelorism, epicanthic folds, a broad nasal bridge with anteverted nostrils, posteriorly angulated ears, micrognathia, widely spaced nipples, arachnodactyly with proximal thumbs, and a coxa vara deformity. The unbalanced translocation was inherited from the mother, who had a reciprocal translocation involving the terminal portions of 2p and 17q. To the best of our knowledge, this is the first report of a liveborn infant with deletion of the distal portion of 17q with the exception of reports of patients with ring chromosome 17. PMID- 4014310 TI - The effect of Mendelian disease on human health: a measurement. AB - We describe an attempt to measure effects of Mendelian phenotypes on human health (homeostasis) in man. We used the McKusick Catalogs as the source for descriptions of autosomal dominant, recessive, and X-linked phenotypes. Three hundred and fifty one entries (76% of the initial sample) were disadaptive causing an impairment, disability, or handicap. (Terms used are in accordance with World Health Organization (WHO) definitions.) Phenotypic effects were scored to measure impact on life-span, reproductive capability, and psychosocial characteristics. We found 1) 25% of the disadaptive Mendelian phenotypes were apparent at birth and over 90% by the end of puberty; age at onset is unimodal in distribution for autosomal recessive and X-linked diseases, and trimodal for autosomal dominant (with modes during morphogenesis, infancy, and early adult life); 2) 58% of phenotypes involved more than one anatomical or functional system; autosomal dominants were more likely to involve only a single system; 3) life-span was reduced in 57%, particularly in those with onset in pre- or intra reproductive life, and more often in recessive and X-linked diseases (data corrected for genetic lethals); prognosis varied with system involvement; 4) reproductive capability was impaired in 69% of phenotypes; and 5) most phenotypes compatible with life beyond infancy caused psychosocial handicap and limited the access to schooling and work. These findings have implications for medical care. PMID- 4014311 TI - The effect of Mendelian disease on human health. II: Response to treatment. AB - We describe an attempt to measure efficacy of treatment in the Mendelian diseases of man. We used the McKusick Catalogs to identify 351 single gene diseases. We scored the impact of each disease in seven phenotypic categories: lifespan, reproductive capability, somatic growth, intellectual development, learning ability, capacity to work, and cosmetic effect. We then scored the success of treatment in ameliorating each of these component manifestations separately and together. The response to treatment was slight in the whole sample (n = 351): lifespan was increased in 15%, reproductive capability in 11%, and social adaptation in 6%. We observed that the mutant gene product was known in only 15% of the conditions comprising our sample. Since the mutant polypeptide is known in most inborn errors of metabolism, the diseases of this type (n = 65) in our sample of Mendelian traits were studied separately. In each of the seven categories of phenotypic impact, only a few of the hereditary metabolic diseases responded in any degree to specific treatment: the treatment gave complete relief in 12%, there was a partial response in 40%, and none in the remaining 48%. These findings have implications for prognosis, genetic counseling, and medical care of patients with Mendelian disease. PMID- 4014312 TI - Osteogenesis imperfecta with unusual skeletal lesions: report of three families. AB - Thirteen individuals with osteogenesis imperfecta (OI) from three families were evaluated. All examined persons with OI had multilocular radiolucent, radiopaque, or radiolucent-radiopaque lesions of the maxilla and mandible. In most patients, the lesions involved the tooth bearing areas, but in two, the rami also were involved. Teeth were normal. Radiologic findings in the extragnathic skeleton included marked coarseness of trabeculae and diffuse osteopenia. It is proposed that these patients represent yet another dominantly inherited OI syndrome. PMID- 4014313 TI - Autosomal recessive deafness with skeletal dysplasia and facial appearance of Marshall syndrome. AB - We report on two sibs born to consanguineous parents with clinical and radiological features closely resembling those previously described by Insley and Astley [1974]. This observation provides further evidence for a distinct autosomal recessive condition with the facial appearance of Marshall syndrome, deafness, and skeletal dysplasia. PMID- 4014314 TI - A method to assess the environment for genetic studies: the Common Environment Index and the Household Relationships Interview. AB - Genetic and environmental influences in causing a disease are difficult to measure because of lack of precision in identification of relevant nongenetic variables. The Household Relationships Interview and Schedule was developed to measure shared common environment in families (Common Environment Index) and to take into account developmental stages throughout the life cycle and separation/disruption. Seven trained persons interviewed three individuals who reported fictitious interrelated life histories varying in length and complexity. Discrepancies between the recorded data and the true data were analyzed. Overall 96.1% of the items were recorded correctly. Thus, the method has shown good face and construct validity and reliability for measuring quantity of time shared by relatives in a common household. Common environment as measured by this instrument should be a particularly useful tool in behavior-genetic studies. PMID- 4014315 TI - A taxonomic approach to the del(4p) phenotype. AB - The findings of 23 patients with the del(4p) phenotype are compared systematically. Three patients with a small deletion evident only on analysis of extended chromosomes have a phenotype comparable to 13 patients with a more extensive chromosomal deletion. Two patients with no detectable deletion also fit into the phenotypic spectrum of patients with del(4p), suggesting the same etiology. Five patients with fewer typical and more atypical findings probably represent a heterogeneous group of other syndromes. Numerical analysis of the phenotype allows one to identify patients who most likely have a deletion requiring a more intensive cytogenetics analysis. PMID- 4014316 TI - Wolf-Hirschhorn syndrome owing to 1:3 segregation of a maternal 4;21 translocation. AB - We describe a child with Wolf-Hirschhorn syndrome with the karyotype 45,XY,inv(9)(p11q13)pat,-4,-21,+der(4),t(4;21)(p15.3;q11.2)mat. This is the second case known to us of Wolf-Hirschhorn syndrome caused by 1:3 segregation of a parental rearrangement. This mode of segregation can be predicted in both cases by a pachytene-diagram model. It is uncertain whether or not the proximal 21q monosomy in this case has affected the phenotype. PMID- 4014317 TI - The heterogeneity problem. I: Separating genetic from environmental forms of the same disease. AB - The purposes of this work were 1) to reparameterize the likelihood used in segregation analysis in a way particularly suited to detecting heterogeneity (the result of the analysis is a parameter giving the proportion of families with the genetic form of the disease in the dataset) and 2) to test how well this reparameterization works using simulation. We assume that a dataset contains nuclear family data, with some of the families having a form of the disease that is environmentally caused and the others with a genetic form of the disease. In this study, we considered the case where the genetic form is a simple recessive and the environmental form a random model. The underlying parameters were the gene frequency, q, and the frequency of sporadics, R. We reparameterized the likelihood in terms of alpha, the percentage of genetic families in the dataset, which we attempt to estimate. We contrast the estimates of alpha with the population heterogeneity as reflected in the estimates of q and R. For the simulation, nuclear families are generated. Genetic families were simulated with a mendelian recessive pattern and environmental families according to a simple random model. Over a wide range of generating parameters, estimates of alpha were good, differing from the "true" values by only a few percent. Estimates of q and R, on the other hand, ranged from fair to poor. Our results indicate that the amount of heterogeneity in a dataset can be accurately estimated using segregation analysis, even when estimates of the gene frequency and penetrance among sporadics are unreliable. PMID- 4014318 TI - The dynamics of quantifiable homeostasis. VI: Processes of fractional order. PMID- 4014319 TI - A preliminary study of serum beta-glucuronidase enzyme activity in progressive muscular dystrophies. PMID- 4014320 TI - Dermatoglyphics in Borjeson-Forssman-Lehmann syndrome. PMID- 4014321 TI - Clinicopathologic correlations in a series of 143 patients with IgA glomerulonephritis. AB - In an unselected series of patients with IgA glomerulonephritis, old age, high blood pressure, and high urinary protein excretion at the time of renal biopsy were found to correlate with impaired renal function, whereas sex, estimated duration of the disease, or high serum IgA levels did not. The following clinical features were favorable prognostic signs: asymptomatic proteinuria, macroscopic hematuria, and isolated microscopic hematuria. The degree of diffuse mesangial alteration and the presence of segmental glomerular lesions correlated clearly with the subsequent clinical outcome. Vascular lesions, i.e. arteriosclerosis and renal vascular deposition of C3, were most often present in patients with severe glomerulopathy. The presence of electron-dense deposits in glomerular capillary walls was also an unfavorable prognostic finding. Renal biopsy findings of interstitial infiltrates of inflammatory cells and IgA distributed along glomerular capillary walls were usually associated with extrarenal manifestations of the disease. PMID- 4014322 TI - Membranous glomerulonephropathy with crescents in systemic lupus erythematosus. AB - Over a 2-year period percutaneous renal biopsies were carried out on 23 patients with systemic lupus nephritis. When classified by immunofluorescence, and light and electron microscopy, 4 patients had mesangial disease, 1 had focal and segmental proliferation, 5 had diffuse proliferation and 5 had membranous changes. 3 biopsies were unclassifiable with end-stage changes and 5 showed an unusual combination of pure membranous changes in association with significant crescent formation. The outcome of the latter group of patients was uniformly poor. We think that this group represents a distinct histological entity with a poor prognosis. PMID- 4014323 TI - Fungal peritonitis in patients on peritoneal dialysis: incidence, clinical features and prognosis. AB - Fungal peritonitis occurred in 17 patients on chronic peritoneal dialysis. The incidence of infection per 100 patient-dialysis months was 0.36 for patients on intermittent peritoneal dialysis and 1.6 for patients on continuous ambulatory dialysis (p less than 0.005). Initial clinical findings included abdominal pain (76%), fever (59%), cloudy dialysate (76%) and poor dialysate outflow (6%). 15 patients received antibiotics within 4 weeks of developing peritonitis. All infections were caused by yeasts, with Candida parapsilosis and Candida albicans as the most common species. 14 patients were unable to continue peritoneal dialysis due to persistent or relapsing infection or the development of complications. 2 of the 3 patients who were able to continue peritoneal dialysis were treated with catheter replacement, intraperitoneal miconazole and oral ketoconazole. PMID- 4014324 TI - Clinicopathological correlation of IgA nephropathy in children. AB - 22 patients with IgA nephropathy aged 7-16 years, 15 of whom were found by mass urine screening of school children, were divided into three groups based on the degree of their proteinuria at admission: group A (n = 6) below 0.5 g/day of urine protein, group B (n = 7) between 0.6 and 3.0, and group C (n = 9) above 3.0 g/day of urine protein. The degree of proteinuria seemed to be related to the severity of pathological changes of the glomerular basement membrane; most severe in group C, moderate in group B, and minimal in group A. IgA deposits in the mesangial area were found in all groups of patients, but those in the capillary walls were most frequently found in group C. In addition to electron-dense deposits in the mesangial area, which was found in all groups of patients, the subendothelial and subepithelial deposits were the most remarkable changes found in group C. During the clinical observation period, which was between 2.0 and 7.1 years, no patient belonging to group A progressed to groups B or C. 4 cases in group C developed chronic renal failure, but none in the other groups did. The amount of urine protein might be used as a valuable parameter of the pathological damage of the glomerulus in children with IgA nephropathy. PMID- 4014325 TI - Disseminated visceral infection with Mycobacterium fortuitum in a hemodialysis patient. AB - A 28-year-old patient with chronic renal failure on maintenance hemodialysis developed fever, granulomatous hepatitis, pulmonary infiltrates, sacroiliitis, and spondylitis which were unresponsive to conventional antituberculous treatment. Cultures of the sputum gave repeated growth of Mycobacterium fortuitum. This organism was resistant 'in vitro' to most antituberculous drugs and sensitive to some aminoglycosides and doxycycline. No mycobacteria were found in the water used for dialysis. The patient was successfully treated with amikacin and doxycycline. Nontuberculous mycobacterial infection should be considered in the differential diagnosis of febrile illnesses resembling tuberculosis in hemodialysis patients. Defective immune mechanisms could contribute to this complication. Since M. fortuitum is usually resistant to antituberculous drugs, precise identification and sensitivity testing are essential for optimal management. PMID- 4014326 TI - Rapidly progressive glomerulonephritis in a patient with rheumatoid arthritis during treatment with high-dosage D-penicillamine. AB - A patient with advanced rheumatoid arthritis and severe clinical manifestations of rheumatoid vasculitis died of acute renal failure after 30 months of treatment with high-dosage D-penicillamine. She had had no signs of adverse drug reactions until the terminal illness. Although streptococcal pharyngitis was diagnosed late in her disease, penicillamine-induced immune complex glomerular damage is considered more likely than poststreptococcal glomerulonephritis, because her microscopic hematuria preceded diagnosis of pharyngitis. Postmortem examination disclosed findings suggestive of rapidly progressive glomerulonephritis of immune complex pathogenesis. The short period of microscopic hematuria and the rapidity of development of renal failure before death emphasize the need for frequent monitoring of renal function and prompt discontinuation of D-penicillamine treatment upon detection of otherwise unexplained hematuria. There is urgent need for early immunological evaluation, renal biopsy, and vigorous therapeutic measures. PMID- 4014327 TI - Hematuria, proteinuria, and hypertension in a patient with multiple organ system disease. PMID- 4014328 TI - Amyloid, carpal tunnel syndrome, and chronic hemodialysis. PMID- 4014329 TI - The changing scene. PMID- 4014330 TI - Experience with the pulmonary artery catheter in obstetrics and gynecology. AB - Although traditionally the exclusive domain of other medical specialties, pulmonary artery catheterization may be of tremendous benefit to a variety of obstetric and gynecologic patients. Our experience with such invasive hemodynamic monitoring in 72 patients in an obstetrics and gynecology service is presented. In 86% of cases, catheter placement and primary management were carried out by residents in obstetrics and gynecology. Although many of the indications for pulmonary artery catheterization encountered are common to other areas of medicine, certain conditions such as severe preeclampsia or rheumatic heart disease in pregnancy involve pathophysiologic conditions unique to our specialty. On the basis of our experience, recommended indications for pulmonary artery catheterization in obstetric and gynecologic patients are presented. Insertion techniques, complications, and clinical outcome are discussed. PMID- 4014331 TI - Lymphatic spread in carcinoma of the vulva. AB - A study of 153 patients with squamous cell carcinoma of the vulva is reviewed. Regional node metastases were present in 20%, and lymphatic spread proved the single most significant prognostic factor in this disease. Recurrent carcinoma developed in 47% of cases with nodal metastases. Lymph node metastases were directly related to stage of disease, tumor differentiation, lesion size, and depth of invasion. Sixty percent of nodal disease was not suspected by clinical examination. No patient developing recurrent disease after identification of positive nodes survived the disease. Surgical staging based only upon size of lesion and presence of nodal metastases appears to offer a clearer prognostic profile than conventional clinical staging. The pattern and frequency of nodal spread suggest that in selected instances modifications of the standard surgical treatment of vulvar cancer may be appropriate. PMID- 4014332 TI - Sterilization failures and their causes. AB - To say that a sterilization failure rate is expected does not answer why. Forty seven cases of repeat sterilization have undergone such surgical and pathologic scrutiny. Resection methods failed most frequently because of spontaneous reanastomosis or fistula formation. Fimbriectomy was particularly vulnerable to reanastomosis because the fimbria ovarica was not removed. Mechanical devices failed when the device was defective, placed improperly, or placed in an improper location. Tissue damage was evident but incomplete when the bipolar electrocoagulation method failures were reviewed, and the endosalpinx remained viable. Unipolar method injuries, in contrast, were complete; they failed by fistula formation. Thus bipolar method failures may occur because of the limited range of electrical power available when using bipolar generators. Some sterilization failures are preventable, but many are not. When medicolegal questions arise, these findings may help answer the question, Why? PMID- 4014333 TI - Evaluation of the use of continuous lumbar epidural anesthesia for hypertensive pregnant women in labor. AB - The use of continuous lumbar epidural anesthesia in women with pregnancy-induced hypertension remains controversial. We retrospectively reviewed the charts of 285 women with pregnancy-induced hypertension who were delivered in a 2-year period. Among 185 vaginally delivered patients who received continuous lumbar epidural or local anesthesia, there were no significant differences in the incidence of maternal hypotension, abnormal fetal heart rate tracings, low Apgar scores, or neonatal intensive care unit admissions. Of 100 patients delivered by cesarean section, the incidence of low Apgar scores, depressed umbilical cord pH values, and neonatal intensive care unit admission was increased among those who received general anesthesia (p less than 0.05). However, general anesthesia patients were more likely to have abnormal fetal heart rate tracings (27% versus 4%) requiring urgent delivery. Thus differences in outcome probably reflect poorer fetal condition prior to anesthesia induction rather than a specific anesthetic effect. These results demonstrate that continuous lumbar epidural anesthesia is safe and effective for both the fetus and the mother with pregnancy-induced hypertension. PMID- 4014334 TI - Twin pregnancy with intrauterine death of one twin. AB - The antepartum death of one twin is a rare obstetric complication. Two cases are presented, accompanied by a review of the current literature. The premature and neonatal death rates are high in the surviving twins. Toxemia, fetal distress, abnormal presentation, and dystocia are also increased. Maternal disseminated intravascular coagulation has been demonstrated without a concomitant fetal coagulation defect. A more unique finding is fetal disseminated intravascular coagulation with a monochorionic placenta. The common circulation between the live and dead twins may result in fetal cerebral, renal, and cutaneous lesions, usually without demonstrable maternal disease. High-risk obstetric management is reviewed and a careful pediatric follow-up is recommended with monozygotic twins. PMID- 4014335 TI - Amniotic fluid embolism: an overview and case report. AB - This article gives an overview of amniotic fluid embolism, which still carries a fatality rate of approximately 86% and which accounts for 9% of all maternal deaths. A case report is presented which ended with a fatal outcome. Photomicrographs show fetal squames and lanugo hairs in the pulmonary capillaries as well as ones aspirated from the right atrium. The treatment is discussed in terms of acute primary and acute secondary care. Acute primary care centers around the prompt recognition and treatment of pulmonary edema. This is apparently due to the mechanical blockade of the pulmonary vasculature and particulate matter from the amniotic fluid and also to an anaphylactoid reaction adding to the pulmonary arteriolar spasm. The acute secondary treatment deals with combating the almost inevitable disseminated intravascular coagulation and uterine atony. Being always alert to the possible occurrence of this condition and being able to institute appropriate therapy rapidly are necessary for a successful outcome. PMID- 4014336 TI - Analysis of 2136 genetic amniocenteses: experience of a single physician. AB - Between 1979 and 1984, 2136 midtrimester genetic amniocenteses were performed by a single physician at the University of California (Davis) Medical Center. The medical records were reviewed for maternal age, amniocentesis indication, ultrasound findings, location of placenta, location of the needle insertion (transplacental versus nontransplacental), color of the amniotic fluid, results of prenatal testing, complications of procedure, and pregnancy outcome. Follow-up data were available for 88% of the pregnancies. There were 38 miscarriages (1.9%), 18 stillbirths (0.9%), and four neonatal deaths (0.2%), resulting in a total postprocedural loss rate of 3.1%. Miscarriage within 2 weeks of amniocentesis occurred in only 0.4% of procedures (seven of 1918). No significant difference in pregnancy outcome was noted between transplacental and nontransplacental amniocentesis. Greenish brown discolored amniotic fluid was found in 3.6% of procedures (76 of 2136). In this group there was a 14.5% fetal loss rate with an overall 22.4% adverse outcome. PMID- 4014337 TI - Abdominal pregnancy: a study of twenty-one consecutive cases. AB - Early abdominal pregnancy is self-limited by hemorrhage from trophoblastic invasion, with complete abortion of the gestational sac that leaves a discrete crater which is sometimes difficult to identify. Advanced abdominal pregnancy survives the hemorrhage of trophoblastic invasion and partial tubal abortion and implants secondarily in the first trimester on any adjacent structure. It may progress to term if not diagnosed or interrupted by abruptio placentae and have spurious labor and fetal death. A case of cornual abortion with secondary implantation on the uterus is discussed. PMID- 4014338 TI - Water-soluble radiocontrast material in the treatment of postoperative ileus. AB - Reviewed was a series of 47 obstetric, gynecologic, and general surgical patients with apparent postoperative ileus who had received an oral administration of water-soluble radiocontrast material. Forty of these patients were found to have an ileus, and seven to have a mechanical small bowel obstruction. In the 40 patients with ileus, prompt resolution of the ileus was obtained, no complications were noted, and the method provided rapid differentiation between ileus and obstruction. This modality of therapy offers an excellent alternative both therapeutically and diagnostically to the traditional treatment of ileus with intravenous fluid, nasogastric suction, and gastrointestinal rest. PMID- 4014339 TI - Adnexal torsion. AB - A series of 128 cases of adnexal torsion and an additional 97 cases where the preoperative diagnosis of torsion was incorrect are reviewed. The diagnosis is uncertain and surgical intervention is likely to be delayed. The adnexa are seldom salvaged despite the fact that torsion infrequently involves a malignant neoplasm. Laparoscopy is an effective means of reducing the number of necessary laparotomies when a diagnosis of torsion is uncertain. PMID- 4014340 TI - Elevated static pressure and pregnancy well-being. AB - Static pressure is defined as the pressure existing at all points in the circulation when the heart is stopped and is a determinant of cardiac output and blood pressure. By using the proposed relationship that static pressure = cardiac output X "resistance to venous return," estimates were made of peripheral static pressure in pregnant women. Measurements of cardiac output and venous resistance were accomplished with indirect plethysmographic techniques. Approximately 65% of pregnant women with complications had elevated values for their estimated peripheral static pressure. It is proposed that estimation of peripheral static pressure has both diagnostic and therapeutic applications in women with complications of pregnancy. PMID- 4014341 TI - The age extremes for reproduction: current implications for policy change. AB - The changing demographic features of births in the United States include an increasing number of older women and a decreasing number of adolescents giving birth. Births in adolescents have lower risks than those in women more than 34 years of age and probably of those more than 30 years of age. There is an increase in complicated pregnancies in the United States, related, no doubt in part, to the above. Older women require more costly, high-technology prenatal care, such as genetic counseling, genetic antenatal diagnosis, amniocentesis, ultrasonography, and electronic fetal heart rate testing. The financing of health care needs to recognize these changes. Detailed studies of the economics of perinatal care, more specific to patient population mix and complication treatment patterns are needed to establish priorities with the payment system to assure appropriate care. PMID- 4014342 TI - The Zavanelli maneuver: a potentially revolutionary method for the resolution of shoulder dystocia. AB - Shoulder dystocia is a perilous complication for the fetus. Suffocation and death are imminent. For the obstetrician, there is insufficient time for consultation. Either he or she is ready with an array of manipulative remedies for sequential application or a disorganized chaos will ensue and chance will determine the outcome. Worthy accoucheurs will have planned for this event and will have selected from the numerous procedures touted for its correction that group he or she intuitively feels will be most effective or, at a minimum, most easily remembered. The Zavanelli maneuver deserves to be on every obstetrician's list. It must occupy a bottom priority, however, until its virtue and applicability, demonstrated to date in but a single case, can be confirmed. All current maneuvers for the treatment of shoulder dystocia are directed to completion of vaginal delivery. The Zavanelli maneuver is predicated on cephalic replacement with subsequent delivery by cesarean section. PMID- 4014343 TI - Obstetric outcome in women with epilepsy. AB - A comparison of 150 pregnancies in women with epilepsy and 150 pregnancies in matched nonepileptic control women showed similar rates of pregnancy-induced hypertension, albuminuria, premature contractions, premature labor, and bleeding in pregnancy. Duration of labor, blood loss at delivery, cesarean section rates, and vacuum extraction rates were also similar among epileptic and control groups. There were five perinatal deaths in the epileptic group and two in the control group. A fetal heart rate tracing during a maternal grand mal seizure showed bradycardia, reduced short-term and long-term variability, and late decelerations suggesting asphyxia. It is concluded that grand mal seizures during pregnancy should be avoided by the use of antiepileptic drugs. Women with epilepsy require antenatal neurological and obstetric follow-up during pregnancy. PMID- 4014344 TI - The fetal biophysical profile in patients with premature rupture of the membranes -an early predictor of fetal infection. AB - A modified fetal biophysical profile (nonstress test, fetal movements, fetal breathing movements, fetal tone, amniotic fluid volume, and placental grading) was serially assessed in 73 patients who presented with premature rupture of the membranes and were not in labor. The last study before delivery was compared with the outcome of pregnancy. The relationships between individual variables and combinations of variables (biophysical scoring) and the outcome of pregnancy--as reflected by the development of chorioamnionitis and/or neonatal sepsis--were determined. These data suggest that the fetal biophysical profile is a useful tool for evaluating patients with rupture of the membranes. Rupture of the membranes by itself does not alter the biophysical scoring of the healthy fetus; however, a low biophysical score (less than or equal to 7) was a good predictor of impending fetal infection in patients with premature rupture of the membranes. PMID- 4014345 TI - The survival of very low-birth weight infants by level of hospital of birth: a population study of perinatal systems in four states. AB - This study estimates differentials in survival among very low-birth weight infants according to hospital of birth, and seeks to determine importance of birth at high-technology centers versus birth at other urban or rural hospitals. Data from four states for 1978 and 1979 were used to estimate survival curves for the first 24 hours of life by type of hospital at birth, birth weight, and race. Significant (p less than 0.0001) differences in survival by type of hospital for both races at birth weights of 1000 to 1500 gm were observed. Smaller disparities were seen at birth weights of 750 to 1000 gm. Differentials in survival by hospital setting emerged in the first few hours after birth, underscoring the effectiveness of neonatal intensive care units in reducing infant mortality and the importance of maternal transport. Differentials persisted throughout the neonatal and postneonatal periods, although differences were attenuated. Prenatal assessment and provider and institutional cooperation can contribute to lowered mortality for high-risk infants and mothers. PMID- 4014346 TI - Fetal echocardiography. V. M-mode measurements of the aortic root and aortic valve in second- and third-trimester normal human fetuses. AB - The aortic root dimension and aortic valve excursion of 43 normal fetuses were recorded with M-mode echocardiography and the measured dimensions correlated with noncardiac measurements (biparietal diameter, head circumference, abdominal circumference, and femur length) and cardiac measurements (diastolic biventricular inner dimension, diastolic left ventricular internal dimension, and mitral valve excursion). The correlation coefficients for the aortic root dimension ranged between 0.87 and 0.95, while those for the aortic valve excursion ranged between 0.78 and 0.87. Regression analysis demonstrated that the best fit of the data was a linear model from which the 5% and 95% confidence limits were computed for individual predictions of aortic root dimension and aortic valve excursion from noncardiac and cardiac measurements. PMID- 4014347 TI - Sympathoadrenal and cardiovascular reactivity in pregnancy-induced hypertension. II. Responses to tilting. AB - Sympathoadrenal and cardiovascular responses to tilting were studied in patients with pregnancy-induced hypertension and healthy control subjects during the last trimester of pregnancy and 8 to 12 weeks post partum. Blood volumes were lower in the patients with pregnancy-induced hypertension during pregnancy (0.065 versus 0.081 L/kg, p less than 0.01) but not post partum. Tilting induced significantly smaller increases in heart rate and arterial plasma norepinephrine concentrations and smaller changes in blood pressure during pregnancy as compared to after pregnancy in both groups. Forearm vascular resistance increased significantly in both groups after pregnancy but only in the patients with pregnancy-induced hypertension during pregnancy. The forearm vasoconstrictor response to tilting was, in fact, totally abolished in the third trimester of normal pregnancy. The hypertensive patients had higher arterial plasma epinephrine levels at rest and greater epinephrine and norepinephrine responses to tilting than the control subjects during pregnancy. Normal pregnancy appears to reduce the circulatory and sympathoadrenal responses to orthostatic stress, presumably because of volume expansion that allows venous return to be better maintained in the upright position. The less pronounced pregnancy-induced increase in blood volume in patients with pregnancy-induced hypertension appears to explain the increased sympathoadrenal and forearm vascular reactivity in this group during pregnancy. PMID- 4014348 TI - Prevention of endomyometritis by local application of antibiotic solution during cesarean section. AB - Previous studies have demonstrated a reduction in the incidence of endomyometritis by using irrigation with 1000 ml of saline as a diluent at cesarean section. In this study 2 gm of cefoxitin sodium in 20 ml of saline solution was used for local application to the uterus and abdominal wound in 100 patients undergoing emergency cesarean section; results were compared to those in 100 patients who received no antibiotic at operation. Six patients in the treatment group developed endomyometritis as opposed to 33 in the untreated group (p less than 0.001) and hospital stay was reduced by almost 2 days (p less than 0.001). Local use of cefoxitin sodium appears effective in reducing the incidence of endomyometritis. A prospective double-blind study, however, is imperative before definite conclusions can be made. PMID- 4014349 TI - Bartholin's cyst: marsupialization or aspiration? AB - Of 34 patients with bartholinitis, two thirds had abscesses and one third had cysts. Aspiration provided not only relief but also material for bacteriologic culture. Ninety-five percent of the abscesses, half of them caused by gonorrhea, could be treated with penicillin and metronidazole. Cysts were not treated with chemotherapy. Cure rate was 85%. PMID- 4014350 TI - Maternal virilization in pregnancy due to an unclassified sex-cord stromal neoplasm. AB - Virilization in pregnancy has been reported with various ovarian neoplasms. Presented is a case of maternal virilization resulting from an unclassified sex cord stromal neoplasm. PMID- 4014351 TI - Fluorescence polarization values of amniotic fluid collected from the vagina after rupture of the membranes. AB - Transvaginal collection of amniotic fluid and the use of a reliable test for fetal lung maturity will provide information needed in the management of patients with premature rupture of the membranes. PMID- 4014352 TI - Severe hypoglycemia associated with HELLP syndrome. AB - Presented is a case of the syndrome of hemolysis, elevated liver enzymes, and low platelet counts, in which severe maternal hypoglycemia occurred 8 hours after delivery. It is proposed that the hepatic pathologic features in this case were severe enough to interfere with glycogenolysis and glyconeogenesis. PMID- 4014353 TI - Disposition of ethanol in maternal blood, fetal blood, and amniotic fluid of third-trimester pregnant ewes. AB - The disposition of ethanol in maternal arterial blood, fetal arterial blood, and amniotic fluid of nine conscious, cannulated pregnant ewes (128 to 137 days' gestation) was determined for 1-hour maternal intravenous infusion of ethanol, 1 gm/kg maternal body weight. The maternal arterial blood and fetal arterial blood ethanol concentration-time curves were virtually superimposable up to 14 hours. The apparent zero-order ethanol elimination rates for maternal arterial blood and fetal arterial blood were similar. There was a time lag in the transfer of ethanol into amniotic fluid relative to fetal arterial blood, and the peak ethanol concentration in amniotic fluid was significantly lower than the concentrations in maternal arterial blood and fetal arterial blood. The apparent zero-order ethanol elimination rate for amniotic fluid was slower, but not significantly so, compared with the ethanol elimination rates for maternal arterial blood and fetal arterial blood. Ethanol-derived acetaldehyde was found in maternal arterial blood, fetal arterial blood, and amniotic fluid at concentrations at least 1000-fold lower than the respective ethanol concentrations. The data indicate that, for administration of this ethanol dosage regimen to the third-trimester pregnant ewe, there is rapid, bidirectional placental transfer of ethanol; elimination of ethanol from the fetus is regulated primarily by maternal elimination of ethanol; the amniotic fluid may serve as a reservoir for ethanol in utero; and there is appreciable acetaldehyde metabolizing capacity. PMID- 4014354 TI - Direct-vision sampling of chorionic villi during extra-amniotic instillation of physiologic saline solution: effect on intrauterine pressure and fetal heart activity. AB - After 150 ml of physiologic saline solution had been infused into the extra amniotic space before first-trimester vacuum aspiration abortion, intrauterine pressure ranged between 16 and 23 mm Hg, thus not more than during Braxton Hicks contractions. At chorionic villi sampling during continuous saline solution infusion, fetal heart activity (beats per 15 seconds) decreased temporarily from about 36 to about 33. PMID- 4014355 TI - Vascular reactivity in the hind limb of the pregnant ewe. AB - The data generated by this study are consistent with the fact that pregnancy and progesterone treatment are associated with an increase in vascular reactivity to phenylephrine and a decrease in reactivity to angiotensin II in the circulation to the hind limb of the ewe. This shows that the way in which vascular reactivity changes during pregnancy is dependent both upon the circulation and the vasoconstrictor being examined. It suggests that sensitivity and contractility could change in opposite directions in this circulation during pregnancy. This will require additional verification, both as to its existence and whether this is an important normal cardiovascular adaptation to pregnancy. PMID- 4014356 TI - 3H-dopamine clearance from the intravascular compartment of the maternal and fetal rhesus monkey. AB - The clearance of epinephrine and norepinephrine from the intravascular compartment has previously been demonstrated in both pregnant and nonpregnant models. With the use of the pregnant rhesus monkey, this study describes the clearance of dopamine from the fetal and maternal intravascular compartments. In both, the dopamine clearance was biphasic with an initial half-life of 1.5 minutes in fetal blood and 1.0 minute in maternal blood. These studies also confirmed that dopamine does not significantly cross the placenta in an intact form. These observations are consistent with those made for the other two major catecholamines. PMID- 4014358 TI - Diabetes and spontaneous abortion. PMID- 4014357 TI - Clearance of 3H-dopamine from the amniotic fluid in the rhesus monkey. AB - Previous studies have suggested that dopamine is the major catecholamine in the amniotic fluid; however, there are few data available concerning the metabolism of this hormone in the amniotic fluid compartment. With the use of acute 3H dopamine injection studies into the amniotic sac of pregnant rhesus monkeys, the dopamine half-life was observed to be 29 minutes, the amniotic fluid volume was 113 ml, the metabolic clearance rate was 164 ml/hr, and the calculated production rate was 436 ng/hr. The biphasic pattern of dopamine clearance from this compartment suggests that it is cleared from the amniotic sac by mechanisms similar to those used in the intravascular compartment. PMID- 4014359 TI - Prenatal screening for hemoglobinopathies. PMID- 4014360 TI - Article does not show harm from midforceps. PMID- 4014361 TI - In defense of midforceps. PMID- 4014362 TI - The role of midforceps in current obstetric practice. PMID- 4014363 TI - Idiopathic nonimmune hydrops: a common entity. PMID- 4014364 TI - Proper documentation of hemoglobinopathies. PMID- 4014365 TI - Tocolysis of eclampsia-associated uterine hypertonus. PMID- 4014366 TI - More on malignant hyperthermia during delivery. PMID- 4014367 TI - Premature rupture of membranes at term. PMID- 4014368 TI - Unusual melanocytic nevi of the conjunctiva. AB - In one patient, an epithelioid cell nevus of the conjunctiva contained numerous large, unpigmented, mononucleated, binucleated, and multinucleated benign appearing nevus cells with abundant cytoplasm and frequent intranuclear vacuoles. Despite their overall size, the cells manifested a low nuclear-cytoplasmic ratio. After a partial excision of the lesion, the remainder spontaneously regressed during a two-year period. Another patient's lesion was dominated by a proliferation of spindle nevus cells developing in a long-standing epibulbar nevus. The spindle cells were moderately pigmented, frequently located within walls of epithelial inclusion cysts, and had benign cytologic features. Finally, in a third patient with the cutaneous B-K mole syndrome, a dysplastic conjunctival nevus developed that featured intraepithelial, atypical melanocytic proliferation with superficial colonization of the substantia propria. This portion coexisted with a deeper, preexistent lesion in the substantia propria that was comprised of orderly nests of unpigmented cuboidal nevus cells surrounded by pigmented, spindle-shaped blue nevus cells--a so-called "mixed nevus." PMID- 4014369 TI - Results of conventional vitreous surgery for proliferative vitreoretinopathy. AB - During a five-year period (1978 through 1982), we used conventional vitreous surgery techniques to treat patients who had recurrent retinal detachment as the result of proliferative vitreoretinopathy. At a six-month follow-up, 24 (33%) of 72 patients achieved total retinal reattachment; 14 patients regained ambulatory vision (5/200 or better) after one operation. Only 12 patients were reoperated on; four achieved retinal reattachment. Anatomic success correlated with a lesser grade of proliferative vitreoretinopathy and an absence of detectable retinal breaks. Creation of iatrogenic retinal tears and broad scleral buckling and an extended interval between the initial detachment and vitreous surgery did not improve the prognosis. PMID- 4014370 TI - The ocular findings in Kniest dysplasia. AB - We studied seven patients who had Kniest dysplasia. All of the patients had congenital severe myopia and vitreoretinal degeneration. Four patients developed rhegmatogenous retinal detachments. Early surgery on one patient resulted in successful reattachment and 20/50 vision at a three-year follow-up visit. Other ocular findings included cataracts in two patients, dislocated lenses in one patient, and blepharoptosis in one patient. PMID- 4014371 TI - Shape factor in the penetration of intraocular foreign bodies. AB - We studied the way in which the shape of a missile striking the eye affects the ease of penetration of the central cornea. The test objects were enucleated pigs' eyes restored to normal intraocular pressure by cannulation of the optic nerve and connection of the cannula to a manometric system of physiologic saline. The shape, size, and weight of the missiles were carefully controlled. We attempted to keep these factors within the range of common civilian experience. Missile speed was measured photoelectrically. For each combination of weight and velocity, penetration of the missile was determined consistently, by the point shape. Penetration was most difficult for the blunt tip and least difficult for the knife-shaped tip. PMID- 4014372 TI - The pathophysiology of proliferative vitreoretinopathy in its management. AB - Cellular proliferation following retinal reattachment surgery frequently results in contraction and subsequent recurrent detachment of the retina, negating an initial successful reattachment. This process has been called by a variety of names, such as massive vitreous retraction, massive preretinal retraction, and, more recently, proliferative vitreoretinopathy. Although a good start has been made by the Retina Society to classify the various types of proliferative vitreoretinopathy, some modifications in the classification are required. The fundamental problem in the treatment of proliferative vitreoretinopathy is a lack of knowledge regarding the factors that stimulate the proliferation of cells. The vitreoretinal surgeon should recognize in the life cycle of this process that stage which an eye with retinal detachment has reached. If there is no active cellular proliferation, then a scleral buckle will usually suffice. If there is traction from epiretinal membranes which cannot be relieved by a buckle, then vitrectomy and adjunct procedures are necessary. If there is active cellular proliferation and epiretinal membranes, then the arguments related to proper timing of vitrectomy must be considered. In cases where the retinal holes can be identified and closed, scleral buckling may be performed with subsequent delayed vitrectomy. In most cases, in my experience, a combination of revision of the scleral buckle is required at the time of vitrectomy and membrane segmentation for proliferative vitreoretinopathy. Until such time as drugs are available to inhibit cellular proliferation or until our basic understanding of the cell biology of this process allows other means of pharmacologic intervention, mechanical approaches will remain necessary for the treatment of the most advanced cases. PMID- 4014373 TI - Fluorescein angiography in reticular degeneration of the pigment epithelium. AB - We studied reticular degeneration of the pigment epithelium by fluorescein angiography in 32 eyes of 50 consecutive patients who had ophthalmoscopic indications of this aging-related entity. In this type of degeneration, fluorescein angiography delineated extensive abnormalities of the retinal pigment epithelium and demonstrated normal-appearing retinal vessels and choriocapillaries in the affected areas. PMID- 4014374 TI - Functional visual loss. AB - Patients with functional loss of visual acuity or visual fields range from the "deliberate malingerer" to the "suggestible innocent." Between these extremes are patients with varying mixtures of fraud and suggestibility. These patients do not, as a rule, have psychiatric disease and do not need to see a psychiatrist. The ophthalmologist must be able to control frustration with these patients to prove that the patient has better visual fields and visual acuity than admitted to, and so that he can perform a careful, dispassionate examination to establish that no organic disease is present. This examination makes it possible to offer believable reassurance to the patient. Simple reassurance seems to be effective therapy. PMID- 4014375 TI - Idiopathic amblyopia. AB - Two children without strabismus, anisometropia, or a history of form-vision deprivation who had normal stereoacuity were amblyopic in one eye. The amblyopia responded to occlusion treatment of the sound eye and visual acuity decreased again after cessation of therapy. There is no explanation for this amblyopia. It is possible, however, that binocularly provoked inhibition of the fovea of one eye was conditioned during infancy by an amblyopiogenic condition such as anisometropia. This inhibition may have continued to be triggered by binocular vision in these patients, even though the original obstacle to fusion was no longer apparent. PMID- 4014376 TI - Slit-lamp microscopic appearance of corneal wound healing after radial keratotomy. AB - Radial keratotomy offers a unique opportunity to study corneal wound healing because the corneas are normal, the fine knife blades disrupt adjacent tissue minimally, no sutures are used, there is minimal inflammation, and few postoperative drugs are administered. We studied corneal wounds with a slit-lamp microscope as they healed from two weeks to three years after radial keratotomy in 84 eyes of 51 consecutive patients enrolled in the Prospective Evaluation of Radial Keratotomy (PERK) Study. One day after surgery, the incisions were surrounded by edema. At two weeks, a dense, gray, diffusely marginated opacity occupied 0.1 mm on both sides of the incision. At three months, the area adjacent to the incision was filled with discrete, fine, gray spicules that protruded at right angles from the incision. At six months, the gray cloudiness had completely disappeared, and the individual spicules were more prominent. By one year, the spicules were disappearing from the anterior portion of the incision and were concentrated primarily in the posterior part of the incisions. At two and three years, the incision scar was fainter and the spicules had disappeared from all but the deep posterior part of the wound. We believe that these spicules correspond to the reorganization of the stroma along the edges of the corneal incision. The persistence of the spicules suggests that wound healing in radial keratotomy may not be complete until two years or more after surgery. PMID- 4014377 TI - Recurrences and bilaterality in the multiple evanescent white-dot syndrome. AB - Multiple evanescent white-dot syndrome recurred in two men (23 and 44 years of age, respectively). One patient had a recurrence in the previously affected eye three years after the initial visual loss; the other patient had two recurrences in the contralateral eye, each separated by two years. Two additional patients (a 28-year-old woman and a 21-year-old man) had bilateral but asymmetric acute involvement. Computerized visual study showed a loss of retinal sensitivity in both eyes, correlating poorly with the clinically observed lesions. Results of electro-oculography were abnormal in the patients with bilateral involvement; results of electro-retinography were abnormal only in the more severely involved eye. Systemic investigation in the two bilateral cases was unrevealing. None of the four patients had experienced a preceding influenza-like illness and all had complete recovery of vision within four to six weeks. PMID- 4014378 TI - Characterization of human uveal melanoma cells by phosphorus 31 nuclear magnetic resonance spectroscopy. AB - We performed experiments to determine the potential usefulness of nuclear magnetic resonance spectra in the diagnosis and follow-up of ocular melanoma. High-resolution phosphorus 31 nuclear magnetic resonance spectra at 109.3 MHz were obtained for human uveal melanoma, Greene hamster melanoma, and normal human diploid fibroblast cells. Phosphate metabolites were identified and their concentrations were shown to vary among the different cell lines. Uveal melanoma cells contain unusually high concentrations of the phospholipid metabolite phosphorylcholine and the phosphodiesters glycerol 3-phosphoryl choline and glycerol 3-phosphoryl ethanolamine. Baseline data are thus provided for studies of the effect of various treatment modalities on uveal melanoma. These initial results suggest that the data provided by high-resolution phosphorus 31 nuclear magnetic resonance spectra can provide useful diagnostic and follow-up data with respect to ocular melanoma. PMID- 4014379 TI - Effects of eye rubbing on the conjunctiva as a model of ocular inflammation. AB - We assessed the effects of eye rubbing on the histologic characteristics and inflammatory cell infiltrate of the conjunctiva. The upper eyelids of 20 adult rats were rubbed during a five-minute period, and then the animals were killed immediately, or at four, eight, or 24 hours after trauma. One eye of each animal was rubbed; the unrubbed contralateral eye served as a control. Counts of mast cells, degranulated mast cells, and inflammatory cells (neutrophils, eosinophils, lymphocytes, plasma cells, and macrophages) were recorded from conjunctival samples from the upper eyelid. Immediately after eye rubbing the conjunctival epithelium was histologically disrupted and 50% of the mast cells showed evidence of degranulation. At four hours after trauma the increase in the number of neutrophils was more than 2,300%. Neutrophils were in the margins in the conjunctival vessels, had migrated into the substantia propria, and were aligned subjacent to the epithelial basement membrane; large numbers of neutrophils populated the epithelium. The four-hour stage was the most dramatic phase of inflammation that occurred from the eye rubbing. At 24 hours there was a significant increase in the number of macrophages. The numbers of lymphocytes, plasma cells, and eosinophils were not significantly changed throughout the study. Our findings demonstrate that eye rubbing histologically disrupts the epithelium and induces significant alteration in the inflammatory cell infiltrate of the conjunctiva. These changes may influence the course of ocular disease. PMID- 4014380 TI - A morphologic and autoradiographic study of cell death and regeneration in the retinal microvasculature of normal and diabetic rats. AB - Cell loss and regeneration were investigated and compared in the retinal microvasculature of age- and sex-matched normal and streptozotocin diabetic rats. Selective pericyte loss in the diabetic rat was characterized by changes in the pericyte to endothelial cell ratio in retinal capillaries isolated for microscopy by the trypsin digest technique. A comparison of 3- and 9-month-old normal rats showed no significant change in the pericyte to endothelial cell ratio (1:2.7). In diabetic animals the ratio was reduced to 1:4.03, which was statistically significant (P less than .001). Premitotic retinal vascular cells in normal and diabetic rats were labelled with tritiated thymidine and the labelling indices calculated from cell counts of trypsin digest preparations. Methyl H3 thymidine was infused continuously over an eight-day period using osmotic mini pumps. The labelling index of endothelial cells (0.33%) in normal rats increased to 0.91% in diabetic animals (P less than .05). The labelling index of pericyte cells in normal animals (0.16%) did not increase significantly (P greater than .05) in diabetic animals (0.19%). A special stain was used to exclude labelled polymorphonuclear leukocytes from the cell counts. PMID- 4014381 TI - Cryptogenic oculomotor nerve palsies in children. AB - We examined two cases of isolated, acquired, unremitting oculomotor palsies in children. The results of systemic, neurologic, and neuroradiologic investigations were normal. Both children were observed for more than two years and showed no additional signs or symptoms. Acquired isolated oculomotor palsies in some cases are not necessarily a harbinger of serious disease. PMID- 4014382 TI - Evolution of benign concentric annular macular dystrophy. AB - In 1974, Deutman described a family with an autosomal dominantly inherited macular dystrophy that he termed "benign concentric annular macular (bull's-eye) dystrophy." Ten years later, we performed a follow-up examination. Some patients complained of deterioration of visual acuity, night vision, and color vision. The macular dystrophy had progressed. The fundus periphery was more involved and in two patients there were bone corpuscle-like pigmentations. Electrophysiologic examination showed increased photoreceptor dysfunction with equal involvement of the rod and cone system. The patients had an acquired type III blue-yellow color vision defect with pseudoprotanomaly. PMID- 4014383 TI - Hematologic reactions to carbonic anhydrase inhibitors. AB - The National Registry of Drug-Induced Ocular Side Effects has received 79 case reports of suspected hematopoietic toxicity caused by carbonic anhydrase inhibitors. Twenty-six of these suspected cases (32%) resulted in death secondary to aplastic anemia, thrombocytopenia, or agranulocytosis. In 54 of these 79, adverse reactions (68%) occurred during the first six months of therapy. PMID- 4014384 TI - A clinical, fluorescein angiographic, and electron microscopic correlation of cystoid macular edema. AB - Electron microscopic findings in an eye removed from a woman who had biomicroscopic and angiographic signs of cystoid macular edema occurring in association with a peripheral choroidal melanoma disclosed evidence that the anatomic basis for the biomicroscopic and angiographic changes was the polycystic expansion of the extravascular compartment of the retina by serous exudate and not, as previously reported, edema of the Mueller's cells. PMID- 4014385 TI - Unilateral esotropia after enucleation in infancy. AB - Five patients developed esotropia in the remaining eye after unilateral enucleation in the first few weeks to months of life. Esotropia was associated with a face turn toward the opposite side and abduction nystagmus with a null point in extreme adduction. Our experience with these patients supports the reflexogenic theory for the development of a type of congenital-infantile esotropia. An intact globe-ocular muscle relationship, even in a blind eye, may have a stabilizing effect on the fellow eye in the first few weeks to months of life, and this should be considered before enucleation is done. PMID- 4014386 TI - Radiation therapy for thyroid eye diseases. AB - Sixty-two patients (28 men and 34 women, 26 to 84 years old) with thyroid ophthalmopathy were treated with approximately 20 Gy of fractionated photon irradiation. Eight of 14 patients with motility problems improved after treatment. Ten of 14 with thyroid optic neuropathy improved or stabilized, but four had recurrences within five months after completion of irradiation. Generally, patients who had disease durations of less than six months responded better than those with more long-term ocular changes. PMID- 4014387 TI - Iris melanomas. AB - Most iris tumors behave benignly, reflecting their small size and the high proportion of nevi and spindle A melanomas. Of 1,043 reported iris melanomas, 31 metastasized (3%). Metastasis from a spindle A melanoma is not known to occur despite documented growth and local recurrence after excision. If known spindle A melanomas are excluded from all reported spindle cell tumors of the iris, the rate of metastasis for spindle cell tumors is 2.6%. Mixed-cell melanomas have a metastasis rate of 10.5% and epithelioid melanomas a rate of 6.9%. The interval between the histologic diagnosis and death from metastases ranged from three months to 12 years, with an average of 6.5 years. Five- and ten-year mortality rates for different cell types cannot be ascertained. Iris angiography may be useful in defining the limits of tumor involvement but is of uncertain value in differentiating benignancy from malignancy. Of the 31 cases with metastases, 21 included information on the type of surgical procedure used to obtain the histologic diagnosis. In 13 of the 21 cases (62%), the tumors were initially involved with either incomplete excision or inadvertent transection before enucleation. PMID- 4014388 TI - The oculocardiac reflex during ophthalmoscopy in premature infants. AB - Of 54 consecutive infants referred for ophthalmoscopy with the pupils dilated, continuous electrocardiographic monitoring showed that 17 (31%) had bradycardia, ranging from 10% to 59% of baseline, coincident with instillation of eyedrops, insertion of an eyelid speculum, pressure on the globe, or stretching of the medial and lateral recti muscles. PMID- 4014389 TI - Rearranged automated keratometer for newborn infants and patients in the supine position. AB - To measure corneal curvature in newborn infants and patients in the supine position, we rearranged an automated keratometer, dividing it into two parts, the power unit and the measuring system. The measuring unit was mounted on a universal stand. We observed no difference in measured value between the sitting and supine positions and no difference in maneuverability. We also examined the effect of a speculum in normal adult subjects in the supine position, in which both the strong and the weak radii and the axis of astigmatism were slightly affected. However, there was no significant difference in the mean values of the strong and weak radii of corneal curvature in 22 eyes of infants with corrected gestational ages of 37 to 43 weeks. The examination was carried out with ease. The mean value of corneal curvature was 7.05 mm and the range was 6.63 to 7.74 mm. PMID- 4014390 TI - Ocular deviation after retinal detachment surgery. AB - Thirty patients with untreated rhegmatogenous retinal detachments underwent complete ocular muscle examinations before scleral buckling procedures. The examination was repeated three weeks, six weeks, three months, and six months after surgery. We found a high incidence of heterotropia after surgery; in most cases this resolved during the first six postoperative months. This resolution progressed from heterotropia to heterophoria to orthophoria. We believe this change results from phoria adaptation. Diplopia occurred in three patients. We found no statistically significant association between this diplopia and the type of surgery used. PMID- 4014391 TI - Fluid dynamics in eyes with rhegmatogenous retinal detachments. AB - Inward and outward permeabilities to sodium fluorescein at the blood-retinal barrier were measured by kinetic vitreous fluorophotometry in ten eyes with rhegmatogenous retinal detachments. Fellow eyes were used as controls. Inward permeability of eyes with detachments was significantly larger than that of controls (P less than .005), suggesting damage to the blood-retinal barrier in eyes with detachments. Outward permeability of eyes with detachment and retinal holes was slightly less than that of controls, but the difference was not statistically significant. However, outward permeability of eyes with detachments and with retinal tears was significantly larger than that of controls (P less than .05). This increased outward permeability may be attributed to the increased fluid flow posteriorly through the break across the retinal pigment epithelium. PMID- 4014392 TI - The clinical significance of the reduced capillary resistance factor in the diabetic patient. AB - A statistical survey in a group of 235 subjects (174 diabetic patients and 61 nondiabetic control subjects) was conducted to evaluate the incidence of reduced capillary resistance factor in respect to diabetic disease, to its duration, and to the severity of retinopathy. To evaluate the capillary resistance we used a cupping-glass method (Parrot's angiosterrometer test). The incidence of reduced capillary resistance proved to increase in frequency with diabetes, with its duration, and with the severity of retinopathy. Thus, reduced capillary resistance represents a negative prognostic element for retinopathy. PMID- 4014393 TI - Progressive cone dystrophy associated with low alpha-L-fucosidase activity in serum and leukocytes. AB - The enzyme activities of acid phosphatase, beta-glucuronidase, N-acetyl-beta-D glucosaminidase, and alpha-D-mannosidase were not significantly different in patients with myopia, retinal detachment, hereditary macular dystrophy, and unusual progressive cone dystrophy. alpha-L-Fucosidase activity in sera was lower in three patients with myopia and in two patients with unusual progressive cone dystrophy than in most of the others. Leukocytic alpha-L-fucosidase activity was lower in those with unusual progressive cone dystrophy. The two unrelated patients with unusual progressive cone dystrophy had slowly deteriorating visual acuity, color vision, and photopic electroretinographic responses, but ophthalmoscopically normal fundi and noncontributory family histories. PMID- 4014394 TI - Argon laser trabeculoplasty as a means of decreasing intraocular pressure from "normal" levels in glaucomatous eyes. AB - We conducted a retrospective study of 67 patients (85 eyes) with severe glaucoma to determine whether argon laser trabeculoplasty could reduce intraocular pressures below the "normal" range. All patients had initial intraocular pressures of less than or equal to 19 mm Hg. Success was defined as a decrease in intraocular pressure of at least 20%, no increase in medications, stable visual field, and no subsequent glaucoma surgery. After an average follow-up period of 30 months, treatment was successful in 31 cases. One half of the failures occurred by six months and 11 failures (30%) occurred after 12 months. Sixteen patients were able to decrease their medications. Two patients achieved intraocular pressures between 6 and 9 mm Hg and 20 between 10 and 12 mm Hg. PMID- 4014395 TI - Clinical evaluation of the Dicon CAT 100 applanation tonometer. AB - A comparison of the Dicon CAT 100 applanation tonometer with the Goldmann tonometer in anesthetized human eyes with normal corneas disclosed high correlations for low, intermediate, high, and mean readings, but regression analysis showed that the y intercept was significantly different from 0 and that the slope was different from 1. The CAT 100 systematically overestimated low intraocular pressure levels and underestimated high intraocular pressure levels and thus is not accurate enough for clinical use. PMID- 4014396 TI - Mydriasis and conjunctival paresthesia from local gentamicin. PMID- 4014397 TI - Susceptibility of Acanthamoeba to surgical instrument sterilization techniques. PMID- 4014398 TI - Iritis after herbicide exposure. PMID- 4014399 TI - Insect sting in a cornea. PMID- 4014400 TI - Idiopathic sectoral corneal endotheliitis. PMID- 4014401 TI - Pneumatic syringe used in fibrovascular membrane surgery. PMID- 4014402 TI - A method of removing displaced silicone tubing from the nasolacrimal duct system. PMID- 4014403 TI - A new subperiosteal glass bead inserter. PMID- 4014404 TI - Retinal detachment in chronic brucellosis. PMID- 4014405 TI - Xerophthalmia rates in children in Ethiopia and Sudan. PMID- 4014406 TI - Prolonged complementary chromatopsia in users of video display terminals. PMID- 4014407 TI - Pseudo-internuclear ophthalmoplegia after surgical paresis of the medial rectus muscle. PMID- 4014408 TI - Fleck retina in Kjellin's syndrome. PMID- 4014409 TI - Avulsed retinal veins without retinal breaks. PMID- 4014410 TI - The role of the occupational therapist-work evaluator. AB - This paper presents the role of the occupational therapist as that of a work evaluator who provides services to injured workers. Therapists, by virtue of their professional knowledge, have a frame of reference for work evaluation and understand the factors that interrupt the work process. In work evaluation, the therapist assists the injured worker to develop work readiness and the physical capacities necessary for working productively. This development takes place in a therapeutic milieu where the "worker" role is regained. The role of the occupational therapist-work evaluator includes work-oriented treatment in the acute care setting, job analysis, work tolerance screening, work capacity evaluation, work hardening, and job market reentry management in the work evaluation and community settings. PMID- 4014411 TI - Work hardening: occupational therapy in industrial rehabilitation. AB - Work hardening, presented in this paper as a "new" service for the industrially injured, is actually well grounded in the traditional models and practices of occupational therapy. From the profession's early roots in industrial therapy to the development of a variety of programs for the industrially injured through the 1950s and 1960s, the historical and philosophical bases of occupational therapy support the use of work as an evaluative and therapeutic medium. What is actually new is the adoption of terminology, technology, and a program format that fits in with the needs of consumers in the 1980s. Recent developments that created the need for the specialized services that occupational therapists are uniquely qualified to provide include growth of private sector vocational rehabilitation, changes in workers' compensation laws, and increasing costs of vocational rehabilitation. This paper describes work hardening in its present form. A case example is given that demonstrates how work hardening can be a cost-effective and time-saving bridge which spans the gap between curative medicine and the return to work. PMID- 4014412 TI - Vocational rehabilitation of the older worker. AB - Work is an important social role. A disability can interfere with a person's work abilities and opportunities at any age. Unfortunately, the older population has received disproportionately little attention in rehabilitation, particularly in vocational rehabilitation. This is true, in spite of the fact that there is a growing population of older persons, with a high prevalence of disability. When returning an older disabled person to work, consideration of his or her particular physical, psychological, and social characteristics is required. This paper discusses the involvement of occupational therapists in the returning of older persons to work. PMID- 4014413 TI - Three frames of reference in work-related occupational therapy programs. AB - This paper discusses the relationship of a theoretical frame of reference to the implementation of a work-oriented program. Three frames of reference in occupational therapy are reviewed, and work-related theories and approaches available to therapists are categorized under each. Examples of the application of various frames of reference are given through an analysis of work programs described in the occupational therapy literature. We recommend that therapists select and apply frames of reference systematically when developing work programs to facilitate the development of a body of knowledge in this area. PMID- 4014414 TI - Specialized accreditation: endangered species in an era of change. PMID- 4014415 TI - Professional development: clinician to academician. AB - Drawing on literature from other professions, this paper identifies factors that occupational therapists should consider when making the transition from clinician to academician. It describes the following four stages of a professional career: apprentice, colleague, mentor, and sponsor. Five academic stages of faculty development are also presented. In addition, the work life of a faculty member is delineated. PMID- 4014416 TI - The use of community networks for chronic psychiatric patients. AB - This paper describes a program, the Work Readiness Seminar, designed in collaboration with a community organization, the Altrusa Club, to respond to needs of chronic psychiatric female patients. The five sessions of the program provide the women with information about everyday survival skills and an opportunity to practice these skills. The excellent role models provided by the Altrusa Club members and the programming of life skills "in vivo" are the strengths of the program. This paper also briefly describes three additional programs that evolved from the Work Readiness Seminar. All four programs use community groups as a resource for teaching life skills to chronic psychiatric patients. PMID- 4014417 TI - Variables that contribute to leadership among female occupational therapists. AB - This study determined which variables differentiated occupational therapy leaders from nonleaders and identified factors that contributed to leadership. The subjects were 405 occupational therapists 36 to 74 years old. Some (79) were leaders in the field, and others (326) were randomly selected members of The American Occupational Therapy Association who did not occupy leadership roles. Eighty-nine percent of the questionnaires were returned. Few demographic differences separated the two groups; however, the findings showed that a substantial portion of the leaders shared experiences in childhood, adolescence, and early adulthood that the nonleaders did not share. Leaders viewed themselves as leaders, desired leadership, and saw leadership as an appropriate activity for women. Their view of the female role was less traditional than that of nonleaders. They married much less frequently; those who did marry had fewer children. Most married leaders' husbands highly supported their wives' leadership activities. PMID- 4014418 TI - Time allocation patterns of occupational therapists in Israel: implications for job satisfaction. AB - This study analyzes the time allocation patterns at work of a sample group of Israeli occupational therapists who function in different roles and specialty areas. The sample consisted of 89 female occupational therapists working in the areas of physical impairment, rehabilitation, psychiatry, and pediatrics. Subjects recorded all of their activities during one work week and rated 23 previously identified occupational therapy activities according to perceived levels of importance. The results indicated that, on the whole, occupational therapists in all areas devoted at least two-thirds of their time to treatment related activities (direct and indirect treatment). The results led us to conclude that the time allocation patterns used may have been conducive to "burnout." Therefore, to facilitate professional growth, we recommend that priorities be set and followed and also that role definitions be adhered to more strictly. PMID- 4014419 TI - Brief or new: toilet independence for the severe bilateral upper limb amputee. PMID- 4014420 TI - Promises to keep: implications of the referent "patient" versus "client" for those served by occupational therapy. PMID- 4014421 TI - Ethics of clinical research. AB - The clinical researcher has certain obligations to subjects and theorists associated with the research being proposed. This article has identified some of the major ethical considerations that characterize "good" research. The related readings will give more information regarding ethics of clinical research. PMID- 4014422 TI - Symposium on nearpoint visual stress. Introduction. PMID- 4014423 TI - Functional case analysis: an interpretation of the Skeffington model. AB - The four components of the model of vision developed by Skeffington are described. The influence of stress induced by reading on the interrelation between accommodation (identification) and convergence (centering) is discussed. The use of a convex lens to reduce the need for adaptive responses is presented. PMID- 4014424 TI - Models of mutual interactions between accommodation and convergence. AB - Several possible models of interactions between accommodation and convergence are compared. Accommodative and fusional vergence effort are predicted for each model using the same set of clinical data. Only one model makes predictions that are consistent with clinical and laboratory observations of fixation disparity. The results support the clinical use of graphical analysis of mutual interactions between accommodation and convergence in the diagnosis of accommodative vergence disorders. PMID- 4014425 TI - Clinical approaches to nearpoint lens power determination. AB - Qualitative and quantitative criteria for prescribing plus lenses at near for prepresbyopes together with 12 behavioral objectives are described. Four quantitative prescription criteria are presented using a combined monocular estimate method-low neutral (MEM-LN) dynamic retinoscopy testing procedure. Each of the four prescription criteria are evaluated relative to an arbitrary +0.50 sphere prescription for seven different observable patterns of accommodative responses at 40 cm. Clinical and research implications of prescribing plus spheres are evaluated relative to the change in proximal stimulus characteristics and the change in accommodative response. Intersystem and intermodal consequences are suggested. PMID- 4014426 TI - Clinical management of nearpoint stress-induced vision problems. AB - Functional vision problems caused by or associated with nearpoint vision stress include: accommodative disorders (insufficiency, ill-sustained, infacility); abnormal heterophorias (esophoria, high exophoria); and vergence disorders. These vision disorders cause problems with acuity, comfort, and performance (efficiency). A combination of lens prescribing, vision therapy, and work/study visual hygiene recommendations can eliminate or greatly reduce nearpoint stress induced vision problems. PMID- 4014427 TI - Determination of the effective diameter for the calculation of equivalent thickness of soft contact lenses. AB - This study determines the effective diameter of soft contact lenses for the calculation of their equivalent thickness by relating the physiological response to the wear of prescription and calibration (constant thickness) lenses in a group of subjects. First a relationship is derived between corneal swelling response and thickness of the calibration lenses. Then, by relating the swelling response obtained with the prescription lens to this relationship, it is possible to determine the equivalent thickness of the prescription lens. After determining the geometry of the prescription lenses it is possible to calculate by an iterative integration technique the diameter of the prescription lens to be used in the determination of equivalent thickness. This diameter is found to differ between plus and minus prescription lenses. The integration diameter for all lens powers was found to be 6.7 mm. PMID- 4014428 TI - Effects of soft contact lenses on contrast sensitivity. AB - This study attempts to resolve the conflicting reports relative to contrast sensitivity function (CSF) and soft contact lens wear. Contrast sensitivity was measured at six spatial frequencies for 19 subjects (38 eyes) when corrected with either spectacles or soft lenses. Measured amounts of residual astigmatism and/or sphere were corrected using a trial frame and lenses. Additionally, data were evaluated on more than one occasion in order to investigate the effect of time upon visual performance with the lenses. The results indicate a measurable decrease in contrast sensitivity for only the highest of the spatial frequencies tested (22.8 c/deg) when soft lenses were worn. For those eyes demonstrating a clinically significantly decrease in contrast sensitivity, responsibility appears to be shared by both the contact lens and the cornea. There were no significant changes in CSF over time. PMID- 4014429 TI - Illusory differences which are stereoacuity test cues. AB - Some persons perceive an illusion of unequal blackness when viewing two equally black rods in a stereoacuity test. With binocular vision, the blacker rod is usually the nearer of the two. If blackness is used as a cue to nearness, a stereoacuity test can be performed successfully without using stereopsis. Nevertheless, stereoacuity obtained by this means is usually inferior to that obtained with distance judgments. For this reason it is advisable to warn subjects against using a blackness difference as a cue to the nearer rod. Those who saw this illusion binocularly also saw it monocularly. Therefore, it is more than just an artifact of stereopsis. One person observed an illusory difference in rod width as well as blackness. PMID- 4014430 TI - Steady-state visual evoked response amplitudes and concurrent electroencephalographic activity. AB - Among the possible causes of steady-state visual evoked response (VER) amplitude variability are: concurrent electroencephalographic (EEG) activity occurring at frequencies other than that of the VER (alpha rhythms, etc.), and EEG activity occurring at the same frequency as the VER (Noise). To evaluate these two factors, 10 steady-state VER's (7.8 Hz pattern reversal rate) and 10 samples of resting EEG activity were obtained from each of 20 normal subjects. The correlations between VER and concurrent EEG activity at other frequencies were calculated from simultaneous determinations of Fourier-derived VER and EEG amplitudes. No significant correlations were found. Because EEG Noise occurring at the same frequency and time as the VER cannot easily be separated from the VER by Fourier transformation, two indirect techniques for assessing the amplitude of this Noise were evaluated: measurement of simultaneously recorded activity at frequencies directly adjacent to the 15.6 Hz VER frequency and measurement of EEG activity at 15.6 Hz obtained just before the VER measurements. Neither of these procedures could predict trial-by-trial variations in the amplitude of the Noise at 15.6 Hz. However, across subjects both procedures provided good estimates of the mean EEG Noise underlying the VER. PMID- 4014431 TI - Glomerular basement membrane discontinuities. Scanning electron microscopic study of acellular glomeruli. AB - Glomerulonephritides which develop necrotizing and crescentic lesions usually have glomerular basement membrane (GBM) disruptions when carefully examined by light microscopy or transmission electron microscopy. Despite numerous excellent and detailed ultrastructural investigations of GBM discontinuities, a complete appreciation of their actual number, appearance, and distribution within a glomerulus has been difficult to achieve by reconstruction of two-dimensional light or transmission electron microscopic images. Selective removal of podocytes by a sequence of lytic and solubilization procedures has been developed which exposes any structural alteration of the GBM to direct examination by scanning electron microscopy. A case of idiopathic, immune-complex-negative, focal segmental necrotizing glomerulonephritis has been studied by this technique, permitting three-dimensional visualization of the GBM defects which result in free communication between the vascular and urinary spaces. These disruptions were distinctive by their frequency within an affected lobule, variable size, and sharply demarcated edges. Application of this technique to human renal biopsies is capable of enhancing our understanding of the morphologic alterations occurring in human glomerulonephritis. PMID- 4014432 TI - Proliferative and morphologic changes in rat colon following bypass surgery. AB - In this study the proliferative and morphologic changes that occur in the colon of normal and dimethylhydrazine-treated rats following surgical bypass of the middle third of the colon are reported. Proliferative changes were measured by estimating accumulated mitotic indexes following vinblastine treatment and morphologic changes were observed with the use of light microscopy and scanning electron microscopy. Data were collected on Days 0, 7, 14, 30, and 72 after surgery. The results show that surgical bypass produces contrasting effects in the segments proximal to and distal to the suture line. In the proximal segment there was morphologic evidence of hyperplasia, although proliferative activity was unchanged except for an increase at 7 days in normal rats. In the distal segment there was a long-lived increase in the mitotic index, although morphologic changes were not seen. The results for DMH-treated rats were similar to those in normal rats. Groups of isolated dysplastic epithelial cells were often seen in the submucosa adjacent to sutures up to 72 days after surgery. Increased lymphoid infiltration was seen in segments proximal to but not distal to the suture line. It is hypothesized that the different responses of the proximal and distal segments may be related to the different embryologic origins of those segments. It is also hypothesized that the seeding of the submucosa with epithelial cells during suturing may be a factor in tumor recurrence. PMID- 4014433 TI - Differences in lectin binding in tissue sections of human and murine malignant tumors and their metastases. AB - Lectin binding to tumor cells in tissue sections of 16 nonmetastatic and 24 metastatic human adenocarcinomas and 5 nonmetastatic and 5 metastatic murine Lewis lung carcinomas (LLCs) was assessed with an avidin-biotin peroxidase technique. In human tumors, Ulex europaeus agglutinin I (UEA I) showed no binding; whereas concanavalin A (Con A), Ricinus communis agglutinin I (RCA I), wheat germ agglutinin (WGA), soybean agglutinin (SBA), and Dolichos biflorus agglutinin (DBA) bound equally to primaries and metastases. However, peanut agglutinin (PNA) bound to less than 5% of cells in 37 of 40 primaries but to greater than 50% of cells in 18 of 24 metastases. In LLC tumors, UEA I and DBA showed no binding; whereas Con A, RCA I, and WGA bound equally to primaries and metastases. SBA bound to greater than 50% of cells in 5 metastases but not to the 5 primaries. There was less than 5% binding of PNA to 10 primary murine tumors after neuraminidase pretreatment of tissue sections but greater than 50% binding in 3 of 5 metastases. These studies indicate, in both human adenocarcinomas and an experimental tumor system, that most tumor cells which metastasize show preferential binding of PNA and SBA. PMID- 4014434 TI - Autoimmune vasculitis resulting from in vitro immunization of lymphocytes to smooth muscle. AB - Lymphocytes sensitized in vitro to syngenic microvascular smooth muscle and transferred to syngeneic recipients produced in vivo microvessel vasculitis characterized by mononuclear cells which adhered to endothelium, infiltrated the vessel wall, and formed a perivascular cuff. A granulomatous type of vascular inflammation was seen in 20% of the affected recipients in which the vessel smooth muscle appeared to be preferentially attacked. These lesions bear a striking resemblance to certain human vasculitides, and the model provides an important means of studying vasculitis as well as general cellular autoimmune disease mechanisms. PMID- 4014435 TI - Immunohistochemical detection of filaggrin in preneoplastic and neoplastic lesions of the human oral mucosa. AB - The distribution pattern of filaggrin in lesions of human oral mucosa was studied with the use of an anti-filaggrin serum raised in rabbits. A peroxidase antiperoxidase method for the detection of filaggrin was applied to specimens from 9 cases of leukoplakia, 5 cases of verrucous carcinomas, 2 cases of carcinoma in situ, and 5 cases of invasive carcinoma. Areas of normal mucosa with different stages of keratinization were available in the same biopsy specimens. The granular layer of normal orthokeratinized epithelium was positive, whereas the horny layer was negative. Parakeratinized and nonkeratinized epithelia stained less than orthokeratinized epithelium. In leukoplakia and verrucous carcinoma, the reaction was irregular both in the granular and the cornified layers. Carcinoma in situ had a virtually negative reaction, and invasive carcinoma exhibited a slight positive reaction in the more differentiated areas. The immunohistochemical demonstration of altered filaggrin patterns in oral lesions correlates well with the degree of epithelial dysplasia and could be a helpful tool in grading white lesions and neoplasms of the oral mucosa. PMID- 4014436 TI - The pathology of experimentally induced cecal amebiasis in gerbils (Meriones unguiculatus). Liver changes and amebic liver abscess formation. AB - The pathogenesis of experimentally induced cecal amebiasis in gerbils (Meriones unguiculatus) was studied from 5 to 60 days after inoculation. Ulcerative lesions were noted 10 to 60 days after inoculation. The sequential development of lesions was asynchronous and progressed from destruction of the interglandular epithelium and of glandular crypt elements to loss of mucosa and formation of granulomatous lesions in the submucosa involving the muscularis mucosae. Pathologic changes in the liver correlated with the formation of ulcerative cecal lesions. Subacute hepatic changes showed lymphocytic portal infiltrate, Kupffer cell hyperplasia, multinucleated giant cells, granuloma formation, and sinusoidal mononuclear and granulocytic infiltrates. Metastatic amebic liver abscesses occurred as early as 10 days after inoculation, and small abscesses were found in the portal areas of the right liver lobe. The sequential development and pathologic manifestation of the infection and the usefulness of the gerbil for the study of human intestinal amebiasis are discussed. PMID- 4014437 TI - The effect of ethchlorvynol on cultured endothelial cells. A model for the study of the mechanism of increased vascular permeability. AB - Ethchlorvynol (ECV), an agent which produces reversible pulmonary edema, was studied for its effects on cultured bovine pulmonary artery endothelial cell (BPAE) and human umbilical vein endothelial cell (HUVE) monolayers. Endothelial cell monolayers 6 days post-confluent were treated with 1 mg/ml ECV for time intervals of from 5 minutes to 15 hours. ECV treatment caused a mild endothelial cell retraction evident at 10 minutes which increased in severity with increasing duration of exposure to ECV. Retraction of endothelial cells resulted in the formation of irregularly delineated gaps between cells, which remained attached to one another by slender filamentous processes. Despite the severity of the endothelial cell lesion, no cell lysis or cell detachment from the substratum occurred. Furthermore, removal of ECV from cell cultures resulted in the reversal of the endothelial cell lesion. Cytochemical distribution of actin microfilaments in control monolayers localized to a dense peripheral band of actin filaments and to a set of interconnected central microfilaments oriented in general parallel to the long axis of the cell. Endothelial cells treated with ECV for as little as 10 minutes showed a loss of F-actin from the dense peripheral band of microfilaments progressing until the dense peripheral band was entirely lost after 4 hours' exposure to ECV. By 4 hours central microfilaments had reorganized into a prominent series of microfilament bundles aligned parallel to each other and to the long axis of the cell. For investigation of a possible loss of attachment sites of actin filaments as the basis for the lesion, the localization of vinculin was examined in control and ECV-treated BPAE monolayers. After 2 hours' exposure to ECV, vinculin localization within monolayers was affected little, if at all. No effects of ECV on intermediate filaments were observed either. It is proposed that the dense peripheral band of actin bundles is important in maintaining well-spread endothelial cells in monolayers and that ECV acts to destroy the integrity of this structure. It is further proposed that a reaction of endothelial cells to ECV in vivo analogous to that seen in tissue culture accounts for the production of pulmonary edema by creating gaps between cells. PMID- 4014438 TI - Tobacco constituents are mitogenic for arterial smooth-muscle cells. AB - Tobacco glycoprotein (TGP) purified from flue-cured tobacco leaves, tar-derived material (TAR), the water soluble, nondialyzable, delipidized extract of cigarette smoke condensate, rutin-bovine serum albumin conjugates, quercetin, and chlorogenic acid are mitogenic for bovine aortic smooth-muscle cells, but not adventitial fibroblasts. The mitogenicity appears to depend on polyphenol epitopes on carrier molecules. Ellagic acid, another plant polyphenol, inhibited arterial smooth-muscle proliferation. These results suggest that a number of ubiquitous, plant-derived substances may influence smooth-muscle cell proliferation in the arterial wall. PMID- 4014439 TI - Effects of anoxic or oxygenated reperfusion in globally ischemic, isovolumic, perfused rat hearts. AB - It has not previously been possible to study the in vitro effects of reperfusion on severely injured isolated perfused hearts because of the development of the no reflow phenomenon, concomitant with the onset of irreversible myocardial cell injury. A new model of ischemic injury which utilizes an intraventricular balloon to allow uniform reperfusion of irreversibly damaged hearts is described. The effects of reperfusion were studied in Langendorff perfused rat hearts after no flow ischemia for 60 and 150 minutes at 37 C. Uniform reflow was facilitated by maintaining the left ventricle at an isovolumic diastolic volume with a balloon during ischemia and removal of the balloon prior to reflow. Reperfusion was with 1) anoxic media, 2) oxygenated media, 3) oxygenated media in the presence of the mitochondrial inhibitor Amytal, or 4) an initial anoxic reperfusion followed by oxygenated media. Injury was monitored by the assay of released creatine kinase (CK) and myoglobin (Myo), by light-microscopic estimates of the percent of cells containing contraction bands, and by ultrastructural changes. CK and Myo were released with anoxic reperfusion, but larger releases occurred with oxygenated reperfusion. Amytal inhibited the oxygen but not the nitrogen component of release. Contraction bands occurred following oxygenated, but not anoxic, reperfusions and were inhibited by Amytal. Following an initial anoxic reperfusion, oxygen caused additional CK and Myo release and produced an increase in the percent of cells with contraction bands, compared with that with oxygen alone. The response of cells to injury was heterogeneous, and the hearts contained cells with a spectrum of ultrastructural changes. Anoxic reperfusion was associated with cellular swelling and oxygenated reperfusion with contraction band necrosis. PMID- 4014440 TI - Extracellular matrix proteins (fibronectin, laminin, and type IV collagen) bind and aggregate bacteria. AB - The normal microbial colonization of sites in the body's tissues by certain bacteria requires that the bacteria first bind to extracellular secreted constituents, cell-surface membranes, or cell matrixes. This study examines two interactions of a variety of bacteria with the cell matrix noncollagenous proteins fibronectin and laminin and with basement membrane (Type IV) collagen. Adherence of bacteria to matrix proteins coated on tissue culture wells was examined with the use of radiolabeled bacteria. Staphylococcus aureus, Streptococcus pyogenes, and Streptococcus sanguis bound well to fibronectin, laminin, and Type IV collagen, whereas a variety of gram-negative organisms did not bind. The interaction of soluble laminin, fibronectin, and Type IV collagen with bacteria was monitored by nephelometry with the use of a platelet aggregometer. S. aureus aggregated in response to fibronectin, laminin, or Type IV collagen. In contrast, gram-negative organisms did not aggregate with these proteins. It appears that fibronectin, laminin, and Type IV collagen can bind and aggregate certain gram-positive bacteria, and this binding is dependent on the surface characteristics of the organism. These adhesion molecules may play a role in the normal colonization of sites by microorganisms and in invasion during infections. PMID- 4014441 TI - Pathologic findings in adenosine deaminase-deficient severe combined immunodeficiency. I. Kidney, adrenal, and chondro-osseous tissue alterations. AB - The authors have reviewed the autopsies of 8 patients with adenosine-deaminase deficient severe combined immunodeficiency disease (ADA-SCID). Several new findings in nonlymphoid organs, including kidney and adrenal gland, and chondro osseous tissue indicate the multisystem nature of this disorder. Examination of renal tissue in 7 of 8 cases showed mesangial sclerosis. This was confirmed in 3 cases by electron microscopy. One case, treated with multiple erythrocyte partial exchange transfusions for several years, had no mesangial sclerosis. Six of 8 cases showed adrenal-gland cortical sclerosis. Chondro-osseous tissue from vertebrae and costochondral junctions of 4 cases examined showed typical alterations previously reported in ADA-SCID such as short growth plates with few proliferating and some hypertrophic chondrocytes. The authors report the new observations of necrotic chondrocytes, as well as large amounts of cellular debris. These changes were not observed in the 2 other patients examined, who received bone marrow or multiple partial exchange transfusions. The distribution and severity of these lesions, their relationship to ADA replacement therapy, and their homology to mice treated with a potent ADA inhibitor suggests that, in addition to lymphoid dysfunction, disordered nucleoside metabolism due to absent ADA activity in ADA-SCID may be the cause of diverse multi-system pathologic changes in tissues which continue to differentiate or mature after birth. PMID- 4014442 TI - Subcutaneous fibromatosis associated with an acquired immune deficiency syndrome in pig-tailed macaques. AB - A spontaneous multifocal subcutaneous fibromatosis is described in 6 pig-tailed macaques (Macaca nemestrina) with simian acquired immune deficiency syndrome (simian AIDS). The lesions consisted of a proliferation of vascular fibrous tissue that was infiltrated by lymphocytes and plasma cells. One animal also had retroperitoneal fibromatosis, which has also been found in this colony of pig tailed macaques. Progressive weight loss, diarrhea, lymphadenopathy, and neutropenia were seen. Peripheral lymph nodes were hyperplastic, and there was splenomegaly. Aggregates of lymphocytes were present in the bone marrow, kidneys, liver, and lungs. Type D retrovirus particles were found in three nodules by electron microscopy; intracytoplasmic type A and budding particles were identified in fibroblasts. In a setting of acquired immunodeficiency, these subcutaneous tumors in pig-tailed macaques present a striking analogy to Kaposi's sarcoma in human AIDS. PMID- 4014443 TI - Insoluble low-density lipoprotein-proteoglycan complexes enhance cholesteryl ester accumulation in macrophages. AB - The interaction of arterial proteoglycans (PGs) and low-density lipoproteins (LDLs) has been postulated to be an important factor in extracellular cholesterol accumulation in the arterial wall. In the present study, insoluble complexes of LDL and PG (LDL-PG) were prepared and their effects on cholesteryl ester accumulation in mouse peritoneal macrophages was tested. The cholesteryl ester content of macrophages incubated with LDL-PG for 3 days was greater than 20 times that observed in cells incubated with LDL alone. The uptake of 125I-LDL by macrophages was markedly stimulated if LDL was incorporated into a complex with PG. However, in contrast to either LDL or acetylated LDL (ALDL), the extent of subsequent degradation of LDL-PG by the cells was reduced. The uptake and degradation of LDL-PG complexes stimulated macrophage incorporation of 14C-oleic acid into cholesteryl oleate 4- to 5-fold over LDL alone; however, esterification was significantly less than that observed with ALDL, even though more LDL-PG was degraded. Ultrastructurally, macrophages incubated with LDL-PG complexes contained lipid droplets as well as numerous phagocytic vacuoles often containing material similar in appearance to insoluble complexes. These results demonstrate that components of the extracellular matrix, such as PG, can modify the catabolism of LDL by scavenger cells. This phenomenon may be potentially important with respect to foam-cell genesis from macrophages in the arterial wall. PMID- 4014444 TI - Uptake and subcellular localization of bacterial lipopolysaccharide in the adrenal gland. AB - For determination of the kinetics of uptake and subcellular localization of lipopolysaccharide (LPS) from LPS-high density lipoprotein (LPS-HDL) complexes in the adrenal gland, LPS-HDL complexes were isolated by immunoaffinity chromatography of 125I-Salmonella minnesota Re595 LPS that had been incubated with 20 mM EDTA-rabbit plasma. After intravenous injection of LPS-HDL complexes in rabbits, preferential uptake of the LPS was observed in the adrenal, so that by 5 hours, adrenal-tissue-bound LPS concentrations (determined by use of 131I BSA blood marker) exceeded all other tissues examined, including liver and spleen, by at least three-fold. For determination of the subcellular localization of LPS, cholesterol-rich (lipid droplet) fractions and cholesterol-depleted fractions were obtained by ultracentrifugation of homogenates of adrenal tissue from rabbits killed at various times after injection of LPS-HDL complexes. As much as 40% of the adrenal-tissue-bound LPS was recovered in the cholesterol-rich fraction 2.5-24 hours after injection of LPS-HDL complexes. Electron-microscopic autoradiographic and immunocytochemical analysis of adrenal cortex of animals killed 5 hours after injection of LPS-HDL complexes demonstrated specific localization of LPS in lipid droplets. These data thus provide direct evidence for the uptake of LPS into the adrenal cortex of animals with intravascular LPS HDL complexes and indicate that further study of the effect of LPS on adrenocortical function is warranted. PMID- 4014445 TI - Mononuclear-cell pulmonary vasculitis in NZB/W mice. I. Histopathologic evaluation of spontaneously occurring pulmonary infiltrates. AB - This report describes the spontaneous occurrence of pulmonary vasculitis in NZB/W mice, a well-characterized autoimmune strain of mice. These mice develop pulmonary vasculitis in an age-related fashion. Mild perivascular and peribronchiolar lymphoid hyperplasia is first seen at 4 months of age and progresses into severe hyperplasia by 8 months. This precedes the development of angiodestructive lesions, which are first noticeable at 10 months. By 12 months of age all mice show multilobe disease characterized by transmural infiltration of the vascular walls by plasma cells, histiocytes, and mature lymphocytes. Mitotic figures and necrosis are rare to absent. Vessel lumens are markedly narrowed and obliterated in severe cases, with focal disruption of the limiting elastic membranes. In mice older than 10 months of age, there is extension of the infiltrate into the interstitium in a manner similar to that of lymphoid interstitial pneumonia. Arteries and veins are equally affected. The cellular infiltrates and pattern of involvement bears similarity to various pulmonary vasculitides in humans. This is the first report of spontaneous pulmonary vasculitis in NZB/W mice. PMID- 4014446 TI - Regulation of glyceraldehyde-3-phosphate dehydrogenase by a cytosolic protein. AB - Stimulation of glyceraldehyde-3-phosphate dehydrogenase (G3PD) activity and accelerated growth occur in cultures of monkey kidney epithelial cells (BSC-1 line) that are exposed to medium with a reduced K concentration (3.2 mM). We recently found that this activation of G3PD was mediated by the appearance of a new cytosolic protein with an apparent molecular weight of 62,000. G3PD and this modifier protein were isolated from BSC-1 cells, and the interaction between them was characterized to define the mechanism(s) of enzyme activation. The enzyme protein was purified from cells grown in control medium (5.4 mM K). The enzyme, in the presence of modifier, exhibited an increase in maximal rate of enzyme reaction and a decrease in the apparent Km for NAD+. Analysis using Dixon plots revealed that the presence of modifier increased the Ki for NADH by two- to threefold. Inhibition by NADH was competitive with respect to NAD+, glyceraldehyde-3-phosphate, and inorganic phosphate. ATP also inhibited enzyme activity in a competitive manner with respect to NAD+; however, the Ki for ATP was similar both in the presence and absence of modifier. These results suggest that one mechanism by which the cytosolic modifier protein stimulates G3PD activity is to decrease product inhibition by NADH. PMID- 4014447 TI - Cell volume and metabolic dependence of NEM-activated K+-Cl- flux in human red blood cells. AB - The effects of incubation in anisosmotic media and of metabolic depletion on ouabain-resistant (OR) Cl--dependent K+ influxes stimulated by N-ethylmaleimide (NEM) were studied in human red blood cells using Rb+ as K+ analogue. The NEM stimulated but not the basal Rb+-Cl- influx measured in phosphate-buffered anisosmotic media was found to be cell volume dependent. When cellular ATP, [ATP]c, was lowered to less than 0.10 of its initial level by exposure to nonmetabolizable 2-deoxy-D-glucose, the NEM-stimulated but not the basal Cl- dependent Rb+ influxes were abolished. Metabolically depleted red blood cells subsequently repleted by incubation in glucose plus inosine regained the NEM inducible Rb+ (K+) transport activity. The difference in the time course of ATP breakdown and Rb+ influx inhibition suggests that energization of the NEM stimulated Rb+ flux by metabolism may involve factors additional to ATP. PMID- 4014448 TI - Effects of metabolic acidosis on viability of cells exposed to anoxia. AB - The effects of metabolic acidosis were examined in isolated rat hepatocytes under substrate-free oxygenated or anoxic conditions. Lowering extracellular pH to 6.6 under aerobic conditions had no deleterious effects on the cells as determined by trypan blue exclusion, lactate dehydrogenase (LDH) release, cellular K+ and Ca2+ content, and ability to increase ATP levels after nutrients and adenosine were added to media. Cytosolic pH was measured in aerobic cells at varying extracellular pH using 6-carboxyfluorescein. By using values for cytosolic pH obtained in this manner together with 5,5-dimethyl[2-14C]oxazolidine-2,4-dione (DMO) distribution data, a method was derived for determining intramitochondrial pH. The pH gradient across the mitochondrial membrane was found not to change with a decrease in extracellular pH from 7.4 to 6.9. At pH 6.9 hepatocytes were protected against anoxic injury as compared with cells incubated at pH 7.5 or 6.6. This protection was manifested by a decrease in vital dye uptake and LDH release, maintenance of higher cellular K+ content, less stimulation of respiration with succinate, improved recovery of ATP levels after return to an oxygenated nutrient environment, and maintenance of normal cellular Ca2+ content after reoxygenation. Recovery of cellular ATP content was independent of ATP levels, total adenine nucleotide pool, and energy charge ratio at the end of the anoxic period. Measurement of cytoplasmic pH in anaerobic cells by [14C]DMO distribution showed progressive cellular acidification with lowering of extracellular pH. The protective effects observed at pH 6.9 are not unique to hepatocytes since isolated renal cortical tubules exposed to anoxia have improved ATP levels on reoxygenation at this pH when compared with tubules incubated at pH 7.5. PMID- 4014449 TI - Spectral characterization of ciliary beating: variations of frequency with time. AB - Ciliary beating frequency in tissue culture from frog palate and isolated lung was optically examined using instrumentation that was adjusted to measure a fraction of the surface area of a single ciliary cell. Consecutive 1-s segments of the analogue signal were fast Fourier transformed (FFT) to obtain a power spectrum. At room temperature, these power spectra changed over time from 1 s to the next. Each spectrum contained several dominant frequencies of similar intensities. Cooling the preparation resulted in a single-peak spectrum that was constant over time. A mathematical model is proposed to simulate these findings. The results and the mathematical model support the hypothesis that ciliary beating frequency fluctuates over short periods of time. PMID- 4014450 TI - Primary culture of duck salt gland. I. Morphology of confluent cell layers. AB - Dissociated avian salt gland secretory cells were maintained in primary culture after plating on hydrated collagen gels. When seeded at 3 X 10(6) cells/cm2, confluent cell sheets formed within 2-3 days, whereas cultures seeded at lower densities formed a complex reticulum of cell aggregates, which remained nonconfluent even after 7 days. Scanning electron microscopy showed that the free surface of 3-day confluent cultures consisted of intermixed convex and flattened cell membranes with prominent junctional boundaries and abundant microvilli. Transmission electron microscopy indicated that these cultures were multilayers of 1-4 cells in thickness. The plasma membranes of the superficial cells were polarized into apical and basolateral regions displaying, respectively, microvilli and interdigitating lateral membrane folds. These membrane domains were separated by shallow occluding junctions, which consisted of both single strands and simple net-like arrays in freeze-fracture images. Underlying epithelial cells retained lateral membrane folds and formed desmosomal contacts with superficial and neighboring cells. These cultures, unlike the intact tissue, allow direct access to the apical and basolateral cell surfaces for electrophysiological analysis of transmural active ion transport. PMID- 4014451 TI - NBD-taurine fluorescence as a probe of anion exchange in gallbladder epithelium. AB - Previous work has demonstrated that after osmotic shrinkage of Necturus gallbladder epithelial cells, their volumes are restored to control levels despite the continued presence of the hyperosmotic medium. It has been proposed that activation of parallel neutral Na+-H+ and Cl--HCO-3 exchangers in the apical membrane is necessary for regulatory volume increase. As an independent technique to determine whether and for how long ion flux through the anion exchanger is actually enhanced by exposure to hypertonicity, fluorescence measurements of N-(2 aminoethylsulfonate)-7-nitrobenz-2-oxa-1,3-diazole (NBD-taurine), a substrate of the anion exchanger in red blood cells, have been made in intact Necturus gallbladder. The cells were loaded with the dye by incubation. The tissue was perfused in a miniature chamber placed on the stage of a microscope and viewed with high-magnification optics combined with video. Fluorescence was monitored at frequent intervals with a photomultiplier tube, and transmittance of the tissue to the laser excitation light was monitored with a photodiode. The epithelium was simultaneously observed with transmitted light to control for changes in focus or lateral movement. Exposure of the tissue to a mucosal medium made hypertonic by the addition of mannitol transiently enhanced the efflux of NBD-taurine from the cells in approximately 70% of the tissues examined. In the presence of the anion exchange inhibitor 4-acetamido-4'-isothiocyanostilbene-2,2'-disulfonic acid (SITS, 100 microM), hypertonicity enhanced NBD-taurine efflux in only 14% of the preparations.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4014452 TI - Absence of significant sodium-hydrogen exchange by rabbit erythrocyte sodium lithium countertransporter. AB - Red blood cells of several mammalian species (e.g., human, rabbit, bovine) possess a countertransport system for Li and Na. We have used rabbit red blood cells to determine the extent of sodium-proton exchange by this countertransporter. Ouabain-insensitive 22Na efflux into phosphate-buffered K acetate media of varying Na concentrations was determined at extracellular pH 7.5 and 6.9. To maintain the intracellular pH at approximately 7.2, most of the acetate in the pH 6.9 medium was replaced by gluconate, a nonpenetrating anion. Extracellular Na strongly (greater than 10-fold) stimulated the 22Na efflux in both high- and low-pH media, but the K1/2 for this stimulation was higher at pH 6.9. This is consistent with a competitive binding of H to the outward-facing transport site. However, the lower pH itself, in a Na-free medium, stimulated the 22Na efflux only very slightly. The 22Na efflux stimulated by lowering the extracellular pH to 6.9 was less than 1% of the stimulation produced by 100 mM extracellular Na. It is concluded that, although H appears to bind to the substrate site of the Na-Li exchanger, there is no significant H transport in the physiological pH range. PMID- 4014453 TI - In vivo membrane potentials of smooth muscle cells in the caudal artery of the rat. AB - Membrane potentials measured in vivo may differ significantly from those measured in vitro in part due to humoral factors, innervation, and wall tension. These studies were initiated to determine whether it is feasible to record membrane potentials from vascular smooth muscle cells in vivo in the caudal artery of the pentobarbital-anesthetized male Wistar rat. Membrane potentials were measured using glass microelectrodes and correlated with systolic, diastolic, and mean blood pressures. For systolic blood pressures between 100 and 140 mmHg the average resting membrane potential was -38.4 +/- 0.48 mV. There was good correlation of systolic, diastolic, and mean blood pressures with membrane potential between 100 and 140 mmHg (r = 0.89, 0.75, and 0.89, respectively). Below 80 mmHg the arterial muscle cells became more depolarized than would be expected if the membrane potential were determined solely by transmural pressure. The depolarized membrane potential at low arterial pressures may be due to enhanced neural input. Spontaneous electrical activity was observed in some of the in vivo cells. When action potentials were present, they were generated at rates between 1-2/s and 6-7/min. These studies indicate that it is feasible to measure membrane potentials from arterial smooth muscle cells in vivo in the caudal artery of the rat. PMID- 4014454 TI - Myosin phosphorylation and contraction of feline esophageal smooth muscle. AB - We tested the hypothesis that phosphorylation of the 20,000-Da light chain of myosin (LC 20) is related to mechanical activation of esophageal smooth muscle. Circular muscle layer strips of cat esophagus were taken from the lower esophageal sphincter (LES) and the distal esophageal body (EB). The LES strips developed tone spontaneously, and the EB strips were tonically contracted with carbachol. Both tissues relaxed in response to electrical-field stimulation. Phosphorylation of the LC 20 was determined in tissues quick-frozen during relaxation and during stress redevelopment after cessation of field stimulation. Stress and phosphorylation levels were low after 30 s of field stimulation, and a rapid contraction followed field stimulation. Phosphorylation in the LES increased from 0.043 +/- 0.029 to 0.328 +/- 0.043 mol Pi/mol LC 20 within 10 s after stimulation of the inhibitory nerves was terminated, while stress was still rising rapidly. Phosphorylation in the LES then declined to a steady-state value of 0.162 +/- 0.034 mol Pi/mol LC 20 after 10 min. Isotonic shortening velocities at a constant afterload following a quick release showed changes with time that were proportional to the level of phosphorylation. This was also true for values of maximal shortening velocity estimated for zero external load and for the rate of stress redevelopment after a step shortening. Comparable measurements were made in the carbachol-contracted EB. These results indicate that visceral smooth muscles, which normally function tonically (LES) or phasically (EB), exhibit an initial rapid mechanical activation associated with myosin phosphorylation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4014455 TI - Human adipose tissue lipoprotein lipase: changes with feeding and relation to postheparin plasma enzyme. AB - An assay procedure using three different methods to recover lipoprotein lipase (LPL) activity from biopsy specimens of human adipose tissue has been developed. Elution of enzyme from small pieces of tissue was performed at 4 and 37 degrees C using a physiological buffer containing heparin and serum. Extraction of enzyme from a tissue homogenate was carried out in the presence of detergent (sodium deoxycholate and Nonidet P-40), which markedly improved the recovery of enzyme activity. It is suggested that elution at 4 degrees C represents extracellular enzyme activity only and therefore theoretically is the closest measure of physiologically active LPL on vascular endothelium, whereas elution at 37 degrees C, in addition, reflects some intracellular enzyme secreted during the incubation period. In female subjects of various relative body weights activity eluted at 37 degrees C as well as detergent-extracted activity were highly correlated with the extracellular activity eluted at 4 degrees C (r = 0.9). Furthermore, all three parameters correlated strongly with LPL activity in post-heparin plasma, suggesting that they are valid indices of physiologically active LPL. The regression of LPL activity in plasma after a 60-min heparin infusion on adipose tissue LPL yielded higher correlation coefficients for activities recorded after elution at 4 and 37 degrees C (r = 0.725 and 0.754, respectively) than for detergent extraction (r = 0.607). Moreover, the increment of adipose tissue LPL after feeding was approximately twice as high for the activity eluted at 4 and 37 degrees C (34%) as for detergent-extracted activity (19%).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4014456 TI - Decreases in ovine fetal cartilage sulfate uptake and serum sulfate during gestation. AB - In vitro assays for [35S]sulfate uptake by ovine fetal costal cartilage were used to assess gestational changes in cartilage metabolism. Addition of 20% normal human serum to the incubation medium increased fetal cartilage [35S]sulfate incorporation into glycosaminoglycans. Both basal and human serum-stimulated uptakes of [35S]sulfate by fetal sheep cartilage decreased from midgestation to full term. The incremental response in [35S]sulfate uptake that was stimulated by human serum decreased as gestation proceeded to full-term. Fetal serum sulfate concentration decreased logarithmically during gestation, raising the possibility that cartilage sulfate uptake might become substrate limited as full term is approached. Perfusion of seven late gestation sheep fetuses for 7 days with Na2SO4 to achieve serum sulfate concentrations similar to those observed earlier in gestation resulted in a 33% increase in mean cartilage [35S]sulfate uptake compared with that of control twin fetuses, but uptake was not increased to values that occurred spontaneously earlier in gestation. These results suggest that the decreasing rate of [35S]sulfate uptake by fetal cartilage during the last half of gestation is associated only minimally with decreasing serum sulfate levels and is most consistent with intrinsic change in resting chondrocyte metabolism during gestation. PMID- 4014457 TI - Effects of [15N]leucine infused at low rates on leucine metabolism in humans. AB - The present studies were carried out to determine whether infusions of [15N]leucine at low rates affect estimates of leucine oxidation and of proteolysis and protein synthesis in humans. Three groups of normal subjects were infused for 3 h with either [15N]leucine at a rate of 0.16 or 0.26 mumol X kg-1 X min-1 or saline using [2H3]leucine and alpha-[14C]ketoisocaproate as isotopic tracers of leucine metabolism. Data were analyzed at steady state using both single- and dual-isotope models. Preliminary studies were carried out to characterize the dual-isotope model in humans using infusions of [3H]leucine and alpha-[14C]ketoisocaproate. In the postabsorptive state estimates of leucine appearance, disappearance, and oxidation derived from the two isotope models were in good agreement. Infusion of stable isotope up to approximately 10% of the leucine carbon flux do not have a significant effect on leucine metabolism, but the data derived from such studies must be properly controlled and interpreted with care because these tracers are not massless. PMID- 4014458 TI - Metabolic adaptation to reduced muscle blood flow. II. Mechanisms and beneficial effects. AB - Increased mitochondrial enzyme activities are induced in rat muscles after common iliac artery ligation, giving a 76-93% blood flow reduction, and 6 days of intermittent muscle stimulation. To elucidate the trigger for this enzyme induction, the acute alterations in the metabolite pattern during contractions were evaluated. More pronounced changes in intramuscular PO2, creatine phosphate, ATP/ADP, lactate/pyruvate, and glycogen were observed in the ligated leg. The benefit of this enzyme alteration was investigated with the hindlimb perfusion technique. Enzymatically adapted and control legs were perfused at reduced flow during contractions. Similar oxygen consumption and glucose uptake but a significantly lower lactate release were observed in the adapted legs. A lower lactate level, lactate/pyruvate, and a better maintained creatine phosphate/creatine were found in the adapted soleus muscle. The results demonstrate that the increase of mitochondrial enzymes is preceded by acute alterations in energy metabolites due to intermittent hypoxia during contractions at reduced flow and that this enzyme adaptation allows the muscle tissue to maintain a lower anaerobic metabolism and a better energy state during exercise. PMID- 4014459 TI - Energy dependence of lung phosphatidylcholine biosynthesis studied with CO hypoxia. AB - The energy dependence of lung phosphatidylcholine (PC) biosynthesis was evaluated by measuring incorporation of radiolabeled precursor substrates by the isolated perfused lung during carbon monoxide (CO)-induced hypoxia. Ventilation with gases containing 75 or 90% CO (plus 5% O2 and 5% CO2) resulted in a mean decrease of lung ATP content by 29 and 53%, respectively, and a significant decrease of [U 14C]glucose incorporation into free fatty acids and the fatty acyl moiety of lung PC. [9,10-3H]palmitate incorporation into lung PC was also decreased by hypoxia but [methyl-14C] choline incorporation was unaffected. For disaturated PC, incorporation of all three substrates was significantly depressed during CO ventilation. These results indicate that lung synthesis of PC is inhibited by alterations of lung energy state. The reactions in lung PC metabolism that are inhibited by this degree of energy limitation are the de novo synthesis of fatty acids from glucose, the acylation of exogenous palmitate, and the remodeling of PC into disaturated PC by the deacylation-reacylation pathway. PMID- 4014460 TI - Saturable and nonsaturable copper and calcium transport in mouse duodenum. AB - Duodenal copper and calcium absorption was evaluated in 30-day-old normal male Swiss mice by an in situ loop procedure. For both ions, the 90-min absorption values yielded a curve that was resolvable into a hyperbolic (saturable) and a linear (nonsaturable) function. The two ions differed, however, in total absorption and the relative importance of the two functions. For copper, the maximum saturable component of transepithelial movement (Jmax) was 127 +/- 2.4 (SE) pmol in 90 min, the apparent half-saturation constant of the saturable process (Kt) was 4.3 +/- 0.7 microM, and the slope of the nonsaturable function was 0.011 +/- 0.006. Thus, when luminal copper equaled plasma copper (approximately equal to 15 microM), only 8% was absorbed, nearly all of which was by the saturable component. For calcium, on the other hand, Jmax was 4.8 +/- 0.1 mumol, the Kt was 27 +/- 2 mM, and the slope was 0.10 +/- 0.01. At luminal calcium concentrations equal to the inorganic plasma calcium (1 mM), calcium absorption was 75%, but only 80% of that was moved by the saturable process. The findings suggest the existence of separate transport mechanisms for copper and calcium. PMID- 4014461 TI - Kinetic and energetic aspects of the inhibition of taurocholate uptake by Na+ dependent amino acids: studies in rat liver plasma membrane vesicles. AB - The kinetic and energetic aspects of the inhibition of taurocholate uptake by the Na+-dependent amino acid L-alanine were studied in rat basolateral liver plasma membrane vesicles. In the presence of an inwardly directed Na+ gradient, alanine (5 mM) reduced the initial velocity of taurocholate uptake to 60% of control and virtually abolished the overshoot. In the presence of a K+ gradient, the slow rate of Na+-independent taurocholate uptake was similar in the presence or absence of the amino acid. Inhibition of Na+-dependent taurocholate uptake increased nonlinearly with alanine concentration (half-maximal inhibition at approximately 1 mM) and plateaued at 5-10 mM. Kinetic studies showed that alanine significantly reduced the Vmax for taurocholate uptake from 6.32 +/- 0.22 to 3.68 +/- 0.21 nmol X mg prot-1 X min-1 but did not significantly affect taurocholate Km (38.4 +/- 3.6 vs. 29.0 +/- 4.9 microM). In contrast, the Na+-independent amino acid 2-aminobicyclo[2.2.1]heptane-2-carboxylic acid did not affect either the initial velocity or peak uptake of taurocholate. The effects of alanine on the driving forces for bile acid uptake were directly assessed by measuring vesicle uptake of 22Na. At early time points, 22Na uptake was faster in the presence of alanine than under control conditions. These findings provide further evidence that Na+-dependent amino acids noncompetitively inhibit Na+-dependent bile acid uptake in association with accelerated dissipation of the transmembrane Na+ gradient and extend previous observations of this phenomenon made in isolated rat hepatocytes [Am. J. Physiol. 245 (Gastrointest. Liver Physiol. 8): G399-G403, 1983]. PMID- 4014462 TI - Nonprotein sulfhydryl compounds in canine gastric mucosa: effects of PGE2 and ethanol. AB - By use of an in vivo canine chambered stomach preparation in which the gastric mucosa was partitioned into two equal halves, the effect of topical 16,16 dimethyl PGE2 (DMPGE2) (1 microgram/ml of perfusate) and 8% and 40% ethanol on tissue levels of nonprotein sulfhydryl compounds was assessed. Both DMPGE2 and 8% ethanol significantly increased (P less than 0.005) mucosal levels of nonprotein sulfhydryls when compared with corresponding mucosa bathed with saline alone. In contrast, mucosa bathed with 40% ethanol showed significantly decreased levels. If mucosa was bathed with DMPGE2 or 8% ethanol prior to exposing the stomach to 40% ethanol, this depletion in sulfhydryl compounds was not observed. Since other experimental observations have shown that exogenously administered prostaglandins and mild irritants (such as low-dose alcohol) can prevent gastric mucosal damage by necrotizing agents (such as high-dose alcohol), our findings are consistent with the hypothesis that nonprotein sulfhydryls may play a role in mediating gastric mucosal protection. PMID- 4014463 TI - Rapid and repeated blood sampling in the conscious laboratory rat: a new technique. AB - A method for obtaining repeated blood samples from conscious rats by translumbar vena cava puncture is presented. Studies performed at laparotomy enabled us to select a 5/8-in., 25-gauge needle as the ideal instrument for aspirating blood. The awake rat is held prone by an assistant and the needle inserted at the level of the first lumbar vertebra in the coronal plane at an angle of 45 degrees from the vertical. We performed the procedure 350 times in 30 rats (100-300 g) at weekly intervals for 8 wk. Each time, we have obtained 2 ml of blood. The time required for obtaining 30 samples is 15-20 min. There have been no complications and only three deaths (mortality rate, 0.9% per puncture); in all three instances the rats jerked free, lacerating the vena cava. The procedure has been performed in guinea pigs and hamsters, with equal ease, without morbidity or mortality. This new technique permits rapid, atraumatic, repeated samplings from awake animals with no morbidity and minimal mortality. PMID- 4014464 TI - Role of lymph flow in intestinal chylomicron transport. AB - In this study we investigated the influence of lymph flow on chylomicron transport. We examined the effects of varying the hydration of the interstitial matrix on chylomicron appearance time and on lymphatic lipid transport rate when a lipid test meal containing oleic acid and 1-monoolein was infused intraduodenally at a constant rate. The three groups of rats tested were control rats (normal interstitial hydration), rats receiving intravenous saline infusion (expanded interstitial matrix), and rats with an attenuated water absorption rate (dehydrated interstitial matrix). This study shows that lymph flow has a profound effect on intestinal chylomicron transport. As lymph flow increased, the chylomicron appearance time (time between the placement of radioactive fatty acid into the intestinal lumen to the appearance of radioactive lipid in the central lacteal) was reduced. When lymph flow exceeded 40 microliter/min, the chylomicron appearance time reached a minimum value of 13.6 min. This minimum chylomicron appearance time probably represents the time required for assembly of absorbed lipid, formation of chylomicrons, and their subsequent discharge into the lymphatics. The chylomicron appearance time lengthened as lymph flow fell. The results of this study underscore the necessity of using steady-state lymphatic lipid output data to assess factors affecting the cellular packaging and release of chylomicrons in the small intestine. PMID- 4014465 TI - Duodenal acidification releases cholecystokinin. AB - We studied the effect of hydrochloric acid (HCl) in the proximal small intestine on release of cholecystokinin (CCK) and secretin and on exocrine pancreatic secretion in conscious dogs with gastric cannulas and modified Herrera pancreatic cannulas. Intraduodenal administration of HCl in a concentration of 50 or 100 mM at rates of 0.05, 0.1, 0.2, and 0.4 mmol/min significantly increased plasma concentration of CCK in a dose-dependent manner, whereas plasma gastrin levels decreased. The increased plasma CCK level paralleled a significant increase in pancreatic trypsin output. Plasma secretin concentration and pancreatic bicarbonate output also increased in response to the acid, and the increase was dependent on the acid loads delivered in the duodenum. Thus, in dogs, HCl in the duodenum releases both CCK and secretin to stimulate pancreatic secretion of bicarbonate as well as enzymes. PMID- 4014466 TI - Glucocorticoid receptors in isolated intestinal epithelial cells in rats. AB - There is evidence that glucocorticoid hormones influence a variety of epithelial cell functions in the small intestine. To exert their effect, glucocorticoids bind to cytoplasmic glucocorticoid receptors (GR), which, following translocation to the nucleus, stimulate mRNA transcription and then protein synthesis and ultimately trigger hormonal actions. To determine the distribution of GR in small intestinal villus and crypt cells, we measured GR activity in enriched villus and crypt cell fractions by use of [3H]dexamethasone. In normal rats GR activity was present in all cell fractions but was lowest in fully mature villus cells of the upper villus and greatest in immature crypt cells. In contrast, 1 wk after adrenalectomy and ovariectomy or sham operation, both of which reduced plasma corticosterone levels, GR activities were comparable in enriched villus cell and enriched crypt cell fractions. Kinetic studies indicated a single class of binding sites with comparable Kd values in villus and crypt cells of normal and steroid-depleted animals, suggesting that there are more glucocorticoid-binding sites in crypt than in villus cells of normal animals. Immature crypt cells may be more susceptible to glucocorticoid modulation than fully mature villus cells in normal rats in view of their higher GR activity. PMID- 4014467 TI - Localization of sites within dorsal motor nucleus of vagus that affect gastric motility. AB - The purpose of our study was to determine the localization of sites within the dorsal motor nucleus of the vagus (DMV) of the cat that when stimulated would increase gastric motility. To do this, two types of experiments were performed. First, the retrograde tracer fast blue was injected into the antrum and pylorus, and labeled neurons in the DMV were identified. Second, electrical stimulation was performed in areas of the DMV labeled with fast blue as well as in nearby areas with no labeling while monitoring gastric motility, arterial pressure, and heart rate. Results from the first type of studies revealed that peak labeling in the DMV occurred between 0.56 and 1.56 mm rostral to obex. Electrical stimulation in this area using 100 microA, 0.2 ms duration pulses, and 50 Hz resulted in increases in antral and pyloric contractions in 20 animals. The magnitude of pyloric and antral responses elicited by stimulation of the DMV generally correlated to the number of cell bodies labeled with fast blue within the DMV. No changes in arterial pressure occurred, and only a slight (-4%) decrease in heart rate was observed. Maximal increases in motility occurred with 20 Hz (antrum) or 100 Hz (pylorus). These increases in motility were maintained even at 200- and 400-Hz stimulation. Ipsilateral vagotomy or pretreatment with propantheline bromide prevented the increases in gastric motility produced by electrical stimulation of the DMV. Electrical stimulation of more rostral sites in the DMV, the medial nucleus of the solitary tract (NTS), and an area within 1.0 mm medial to the DMV resulted in attenuated or no motility responses. Stimulation of the medial nucleus of the NTS did result in pronounced slowing in heart rate (-61 +/- 21 beats/min). These results suggest that there is a localization of a "stomach area" within the DMV and that electrical stimulation of this area results in gastric motility responses that are mediated by vagal fibers projecting directly to the stomach. In addition, electrical stimulation of the DMV results in selective effects on the gastrointestinal tract in that no pronounced changes in heart rate and arterial pressure occur. PMID- 4014468 TI - Gastrointestinal myoelectric activity in conscious guinea pigs. AB - Myoelectric activity was recorded from the gastric antrum and small intestine of conscious, unrestrained guinea pigs using bipolar Ag-Ag chloride electrodes that had been previously implanted under pentobarbital sodium/Innovar anesthesia. In fasted guinea pigs, the migrating myoelectric complex (MMC) was recorded from the small intestine and was observed to propagate aborally at a speed that declined with distance from the pylorus (range of speeds of the front of phase 3: 17.5 cm/min in the duodenum to 4.1 cm/min in the ileum). The complex was not disrupted by feeding but occurred less frequently in the freely fed state (82-min cycle period in the fasted state versus 139 min in the fed state). The complex started in the duodenum and was accompanied by a brief (6.3 +/- 0.9 min) period of inhibition of antral myoelectric activity. Slow waves were also recorded from the gastric antrum (10.3 +/- 1.3/min) and the small intestine. The frequency of intestinal slow waves was uniform along the length of the bowel (26.2 +/- 1.3/min in the duodenum to 24.7 +/- 1.3/min in the ileum). It is concluded that the guinea pig is similar to other mammalian species, so far examined, in its pattern of gastrointestinal myoelectric activity. PMID- 4014469 TI - Evidence for transcellular osmotic water flow in rat proximal tubules. AB - To determine the predominant pathway for transepithelial osmotic water flow, the transepithelial osmotic water permeability [Pf(TE)] and the apparent dimensions of paracellular pores and slits were determined in rat proximal convoluted tubules microperfused in vivo. To measure Pf(TE), tubules were perfused with a hyposmotic, cyanide-containing solution. Pf(TE), calculated from the observed volume flux in response to the measured log mean osmotic gradient, was 0.12-0.15 cm/s, assuming sigmaNaCl equal to 1.0-0.7, respectively. The dimensions of the paracellular pathways were determined using measured sucrose and mannitol permeabilities (nonelectrolytes confined to the extracellular space). These were 0.43 and 0.87 X 10(-5) cm/s, respectively. By using the ratio of these permeabilities, their respective free solution diffusion coefficients and molecular radii, and the Renkin equation, the radius of the nonelectrolyte permeable pores and the total pore area/cm2 surface area/channel length were calculated to be 1.4 nm and 3.56 cm-1, respectively. Similar calculations for slits yielded a slit half-width of 0.8 nm and a total slit area/cm2 surface area/channel length of 3.16 cm-1. The osmotic water permeability of these nonelectrolyte-permeable pathways was calculated by Poiseuille's law to be 0.0018 cm/s (pores) or 0.0014 cm/s (slits), at most 2% of Pf(TE). We conclude that the nonelectrolyte-permeable pathway in the tight junctions is not the major route of transepithelial osmotic water flow in the rat proximal tubule. PMID- 4014470 TI - Dynamics of glomerular filtration in the river lamprey, Lampetra fluviatilis L. AB - Hydrostatic pressures decreased in the dorsal aorta (from 21.6 +/- 2.0 to 18.7 +/ 0.2 mmHg), proximal (from 19.5 +/- 1.6 to 16.2 +/- 1.7 mmHg) and distal (from 16.7 +/- 0.7 to 13.2 +/- 0.9 mmHg) renal arteries, and glomerular capillaries (from 16.1 +/- 1.1 to 12.3 +/- 0.6 mmHg) of anesthetized lampreys transferred from freshwater to isosmotic 20-30% seawater. Maximal vascular resistance appeared to be in the efferent arteriole; there was a 67% decrease in pressure between glomerular and peritubular capillaries. Plasma oncotic pressure was unchanged. The calculated afferent effective filtration pressure decreased by 87% after transfer and showed a good correlation with single nephron filtration rate. Effective renal plasma flow was high but variable in freshwater lampreys and decreased by 84% after transfer, but glomerular filtration rate did not decrease proportionately and there was a nonsignificant increase in mean filtration fraction from 0.045 +/- 0.022 to 0.080 +/- 0.021. Calculation of glomerular efferent oncotic pressure indicated that filtration equilibrium did not exist in freshwater lampreys but was attained after transfer. The mean coefficient of filtration of freshwater lampreys was 0.028 +/- 0.002 nl X s-1 X mmHg-1. PMID- 4014471 TI - Responses of the normal rat kidney to sequential ischemic events. AB - This study was undertaken to help define how one episode of renal ischemia, insufficient to cause acute renal failure, influences the susceptibility of the kidney to a second more severe ischemic event. Female Sprague-Dawley rats underwent either 15 min of bilateral renal artery occlusion (RAO) or sham RAO. They were subjected 30 min, 3.5 h, or 24 h later to 25 min of RAO. Renal function (GFR, BUN, creatinine), histology, and adenine nucleotide concentrations were compared before and after the 25-min ischemic event. Only the rats with a 30-min hiatus between the 15- and 25-min bouts of RAO had significantly worse renal failure than controls subjected to a single 25-min ischemic event. Three findings were noted only in the rats with increased susceptibility: tubular cell swelling and luminal membrane injury prior to 25 min of RAO and a relative failure of ATP formation immediately following 25 min of RAO. Susceptibility to 25 min of RAO did not correlate with preischemia ATP content. CONCLUSION: prior mild ischemic injury transiently lowers renal resistance to a second ischemic event. Normal resistance is rapidly restored once improvements in prior cell membrane injury, cell volume regulation, and cellular energetics occur. However, resistance to additional ischemia can be normal despite persisting depressions in renal ATP content. PMID- 4014472 TI - Tubuloglomerular feedback activity in virgin and 12-day-pregnant rats. AB - Tubuloglomerular feedback activity was evaluated by micropuncture and microperfusion techniques in virgin and 12-day-pregnant Munich-Wistar rats. Plasma volume increases in pregnancy, which could suppress feedback activity, thus contributing to the rise in glomerular filtration rate observed in normal midterm pregnancy. Late proximal tubules were microperfused at 0, 10, 20, and 40 nl/min and the resulting filtration rate in the same nephron was evaluated. Nephron filtration rate (SNGFR) in proximal and distal tubules of other nephrons was also measured to assess the degree of activation of the tubuloglomerular feedback system and the relation of the spontaneous (normal) late proximal flow rate and SNGFR (distal tubule collections). SNGFR decreased significantly (from the 0 nl/min perfusion value) when late proximal tubules were perfused at 20 and 40 nl/min in both virgin and 12-day-pregnant rats. Tubuloglomerular feedback activity was not suppressed in pregnancy, but the relationship between SNGFR and late proximal tubule perfusion rate was reset for a higher value for SNGFR. The difference between proximal and distal SNGFR suggests that the feedback system was more activated in the virgin than in the pregnant rat. Thus, in spite of the known increases in plasma volume that occur in pregnancy, the kidney does not sense this volume expansion as a stimulus to suppress feedback activity. PMID- 4014473 TI - Effect of barium on cell volume regulation in rabbit proximal straight tubules. AB - Rabbit proximal straight tubules swell abruptly when exposed to hypotonic medium but then shrink in a few minutes as they approach their base-line volume following loss of solute and water. Potassium, the major intracellular cation, as well as sodium, is lost during this process. In the present experiments, we studied hypotonic cell volume regulation in the presence of barium, an agent reported to decrease potassium permeability. Exposure to BaCl2 significantly prolonged hypotonic volume recovery in a dose-dependent manner. Tubules depleted of potassium and loaded with sodium chloride by exposure to 10(-4) M ouabain for 1 h swelled osmometrically and subsequently volume regulated in dilute medium. Volume regulation in such tubules is a consequence of transbasement membrane hydrostatic forces. By contrast, tubules similarly loaded with sodium, but also exposed to 10(-3) M BaCl2, volume regulated only minimally in dilute medium, suggesting BaCl2 might also affect sodium movement. However, hypotonic volume regulation was restored in sodium-loaded BaCl2-treated tubules when cells were more effectively depleted of potassium by incubation in 0-mM potassium medium. We conclude that barium retards hypotonic volume regulation primarily because of its effect on potassium movement. PMID- 4014474 TI - Lack of potassium effect on Na-Cl cotransport in the medullary thick ascending limb. AB - The effect of potassium on sodium chloride uptake into rabbit renal medullary thick ascending limb of Henle's loop (mTALH) cells was studied to assess whether K participates in the Na-Cl cotransport system. Na uptake into the mTALH cells was inhibited 70% at 3 min by 1 mM furosemide. The total and furosemide-sensitive Na uptake was stimulated by Cl. Additionally, Cl uptake into the mTALH cells was stimulated by Na gradients and inhibited 42% at 3 min by 1 mM furosemide. Na uptake was studied in the presence of 0,5, or 140 mM external K gradients. Na uptake was similar in the absence and presence of K. Additionally, furosemide inhibited Na uptake as effectively in the absence or presence of K. Similar studies were conducted to study the effects of Na on 86Rb uptake. Na did not stimulate 86Rb uptake. The uptake of 86Rb was similar in the presence of 0,5, or 140 mM Na gradients. Furosemide had no significant inhibitory effect on 86Rb uptake. Barium (5 mM), an inhibitor of K conductance pathways, inhibited total 86Rb uptake by 19%. In the presence of 5 mM BaCl2, Na still did not have a stimulatory effect on 86Rb uptake. The results confirm the existence of a Na-Cl cotransport system in mTALH cells, but a direct effect of K on the NaCl cotransport system could not be demonstrated under the experimental conditions we used. PMID- 4014475 TI - Renal hydroxybutyrate and acetoacetate reabsorption and utilization in the rat. AB - Is the renal conservation of ketones effected through saturable transport systems? Does the renal reabsorption of ketoacids limit their utilization? The reabsorptive transport (T) and metabolic utilization (Q) of D-3-hydroxybutyrate (HB) and acetoacetate (AA) in the kidney were measured in anesthetized rats by use of clearance and arteriovenous extraction determinations. THB and TAA increased in proportion with increasing HB and AA filtered loads. Fractional THB decreases from 0.97 to 0.72 upon increases in the plasma HB. Fractional TAA also decreases from 0.89 to 0.73, at a constant filtered AA load, when the filtered HB load increased. Thus both saturable and nonsaturable components effect the reabsorption of HB and AA. Renal QHB increased from 0.4 to 4 mumol X g-1 X min-1 on increase in the plasma HB. THB always exceeded the simultaneously measured QHB. However, QHB was significantly correlated with THB, suggesting that QHB may be limited by delivery of HB to the renal cells through reabsorptive pathways. There was no net renal conversion of HB and AA. Both HB and AA were utilized by the kidney. Thus, utilized ketoacids must have entered pathways for complete oxidation or for synthesis (lipid?) in the kidney. PMID- 4014476 TI - Dietary protein intake conditions the degree of renal vasoconstriction in acute renal failure caused by ureteral obstruction. AB - Whole kidney inulin (CIn) and PAH (CPAH) clearances were measured after unilateral release of bilateral ureteral obstruction (BUO) of 24-h duration in rats fed for 4 wk isocaloric diets containing either 40% casein (high protein diet) or 6% casein (low protein diet). Values for CIn and CPAH were markedly depressed in both groups but to a greater extent in high protein-fed rats, averaging less than 60% of values measured in low protein-fed animals. Captopril, an inhibitor of the angiotensin I converting enzyme, increased CIn and CPAH markedly but comparably in high or low protein fed rats. Micropuncture studies performed after unilateral release of BUO in another group of rats fed a high or a low protein diet revealed lower levels of glomerular plasma flow rate (QA) and single nephron glomerular filtration rate (SNGFR) in rats fed a high protein diet. Values for renal arteriolar resistances were nearly twofold in high as compared with low protein-fed animals. Infusion of OKY-1581, an inhibitor of thromboxane A2 synthetase, increased both QA and SNGFR, decreased arteriolar resistances, and increased glomerular capillary ultrafiltration coefficient in high but not in low protein-fed rats. Urinary thromboxane B2 excretion per milliliter of GFR was greater in rats fed a high protein diet than in those fed a low protein diet after release of BUO but not in normal rats. In normal rats infusion of OKY-1581 did not increase CIn or CPAH.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4014477 TI - Cyanate and temperature regulation in anephric rabbits. AB - Knochel and Seldin proposed that the lowered body temperature observed during uremia was caused by an elevation in the circulating levels of cyanate. To test this hypothesis, normal rabbits were infused with varying concentrations of sodium cyanate. Infusion of pharmacological doses of cyanate (plasma concentration rose to 1,080 +/- 70 microM, n = 5) resulted in reductions in body temperature similar to that found during uremia; however, when normal rabbits were nephrectomized the plasma cyanate concentration only rose from 3.7 +/- 1.6 to 18 +/- 1.8 microM (n = 8) by 1-day postnephrectomy (body temperature fell 0.33 +/- 0.1 degrees C, n = 6). Plasma cyanate concentration did not rise further on days 2 and 3 postnephrectomy, despite a continued fall in body temperature. Infusion of cyanate in control rabbits to plasma concentrations attained 1-3 days postnephrectomy did not result in a fall in body temperature. Based on the failure of pathophysiological concentrations of cyanate to cause a reduction in the body temperature of normal rabbits, we conclude that cyanate is not responsible for the lowered body temperature associated with the acute response to uremia. PMID- 4014478 TI - Slow inward current may produce many results attributed to IX1 in cardiac Purkinje fibers. AB - We have tried to answer two fundamental questions concerning the outward current IX1 of cardiac Purkinje fibers. 1) Is it possible that current changes identified as arising from IX1 in voltage-clamp experiments are actually manifestations of changes in the slow inward current (Isi); and 2) is IX1 in fact required to produce the electrical phenomena attributed to it? Isi behavior and the role of IX1 were explored using computer simulation. The Isi model produced current changes during depolarizations and hyperpolarizations from depolarized resting potentials like those attributed to IX1. It also produced a component of "tail currents" that behaved like IX1. If these current changes were analyzed, assuming that an outward current is responsible, the resulting kinetics and current voltage relation would be very similar to the kinetics and current voltage relation reported for IX1. Using the McAllister, Noble, and Tsien formulation of the Purkinje fiber action potential, we found that IX1 is not essential for repolarization of the reconstructed action potential nor is it needed to reproduce interval duration effects and the effects of applied current in that model. Data suggesting that calcium channel blockers reduce IX1 and that catecholamines increase IX1 may be explained as arising from changes in Isi. Thus many manifestations of IX1 can be explained as arising from unanticipated behavior of Isi, and IX1 does not necessarily play a key role in generating Purkinje fiber electrical activity. PMID- 4014479 TI - Differential responses accompanying sequential stimulation and ablation of vagal branches to dog heart. AB - Electrical excitation of small thoracic vagal branches elicited highly localized responses in the canine heart. Specific pathways to the sinoatrial nodal (SAN) regions were identified from negative chronotropic responses to stimulation (20 Hz, 5.0 ms, 3.0-5.0 V) of these branches. Pathways to the atrioventricular nodal (AVN) region were determined from changes in A-H interval (His bundle electrogram) and incidence of heart block as vagal branches were stimulated during concurrent atrial pacing. A few small branches influenced a single cardiac function (atrial rate, contractile force, or AV conduction). More commonly, activation of such branches elicited simultaneous chronotropic and dromotropic effects. However, many branches failed to elicit any detectable cardiac change. The major outflow from the left vagus to SAN and AVN regions is by way of cardiac branches from the recurrent laryngeal nerve at its reflection around the aorta. Activation of the left recurrent nerve reduced atrial rate by 43% and doubled A-H interval 84 to 167 ms. The right thoracic vagus or its branches induced A-H prolongation from 78 to 131 ms. H-V intervals remained constant at a mean of 35 ms. Outflows from the right thoracic vagus to SAN and/or AVN regions originated just below the middle cervical ganglion and at all levels down to the azygos vein. PMID- 4014480 TI - Polarographic measurement of ascorbate washout in isolated perfused rabbit hearts. AB - To study the myocardial washout of ascorbate, the applicability of polarographic detection of ascorbate ions by a platinum electrode (sensitive area 0.03 mm2) was investigated, in both a calibration setup (sampling flow along the electrode: 100 microliter X s-1) and isolated, retrogradely perfused rabbit hearts. In the calibration setup at pH 7.4, the sensitivity of the electrode was 70 microA/mol. This sensitivity increased moderately with increasing pH (13%/unit pH) and increasing sampling flow rate (14% at an increase from 100 to 150 microliter X s 1). In the isolated hearts, ascorbate infused into the aorta was detected in a right ventricular drain by the electrode as well as by the use of 14C-labeled ascorbate. Both recorded time courses were similar except for a scaling factor dependent on flow velocity. During continuous infusion the arteriovenous difference of ascorbate was 2 +/- 2% (SD), indicating a relatively low consumption of ascorbate by the isolated heart. We conclude that polarographic measurement of ascorbate in the coronary effluent of an isolated rabbit heart can be performed on-line and relatively easily. PMID- 4014481 TI - Effects of anesthetics on regional hemodynamics in normovolemic and hemorrhaged rats. AB - Twenty-nine male Sprague-Dawley rats were divided into four groups based on anesthetic exposure, i.e., awake animals and those receiving anesthesia produced by chloralose-urethan, pentobarbital, or by midcollicular brain stem transsection. Before and after hemorrhage (30% of the estimated blood volume), cardiac output (CO) and regional blood flows were measured by the microsphere method. Arterial blood gases and lactate (L) and pyruvate (P) were also determined. CO and regional blood flows were greatest and the L/P ratio was least in awake animals both before and after hemorrhage. In normovolemic rats, the frequency of altered values (as compared with those in awake animals) was similar for all anesthetic techniques, whereas the CO and regional blood flow responses to hemorrhage were altered less frequently in decerebrated animals. Decerebration may be the preferable procedure if the intent is to produce responses in anesthetized animals similar to those in awake rats. If the intent is to study hemodynamics in a specific organ, the selection of an anesthetic technique should be guided by the individual anesthetic effects on that particular tissue. PMID- 4014482 TI - Capillary pressures in rat intestinal muscle and mucosal villi during venous pressure elevation. AB - Whole-organ experiments designed to estimate the capillary filtration coefficient require information about the numerical relationship between capillary pressure and venous pressure. Indirect estimates using isogravimetric and isovolumetric methods indicate that 62-85% of a step change in venous pressure reaches the intestinal capillaries, taken as a whole. We have made direct measurements of capillary pressure with a servo-null micropressure system in the microcirculation of both the intestinal muscle and the mucosal villi of rats during local elevation of venous pressure. Consistent regional differences in the relationship between capillary pressure and venous pressure were observed. During increased venous pressure, submucosal arterioles constricted, while muscularis arterioles dilated. The diameter changes of the small arterioles were consistent with blood flow redistribution from mucosa to muscle during venous pressure elevation, but inconsistent with a pure myogenic response. These data raise questions about the exact role for the expression of the myogenic response during venous pressure elevation in the intestine and about previous interpretations of whole-organ experiments concerned with intestinal blood flow and fluid exchange. PMID- 4014483 TI - A simple method for reducing cardiac output in the conscious lamb. AB - We have developed a method for reducing cardiac output in a controlled stepwise fashion using awake, intact, unsedated lambs. The method involves placing a balloon-tipped (Foley) catheter into the right atrium from a jugular vein isolated by a small neck incision. Systemic venous return and cardiac output are limited by balloon inflation. With each balloon inflation the animal reaches a new and stable cardiac output, which allows the measure of steady-state hemodynamic and metabolic variables. We have been able to decrease cardiac output to as low as 20% of the resting cardiac output and maintain a stable preparation. The reductions in cardiac output are quickly reversible by balloon deflation. Animal survival allows repeated study. We present data from five lambs studied between 26 and 36 days of age. Alterations in O2 consumption, O2 transport, O2 extraction, blood pressure, and arterial lactate concentration are examined in response to decrements in systemic blood flow and are consistent with changes seen in response to a reduction of cardiac output by other methods. PMID- 4014484 TI - Response of canine cardiocyte lysosomes to ATP. AB - The present study was designed to evaluate the relationship of adenosine triphosphate (ATP) to maintenance of cardiac lysosome latency. Highly latent lysosomes were isolated from adult canine ventricular myocytes or cardiocytes and exhibited latency values (based on % free N-acetyl-beta-glucosaminidase, NAGA) of 29.3 +/- 4.7% (SE), minimal cross contamination by mitochondria (less than 2% cardiolipin by weight) and only 1.68% of the total cytochrome c oxidase activity; enzymatic enrichments ranged from 10-fold for NAGA to almost 50-fold for cathepsin B. Incubations of cardiocyte lysosomes at pH 7.0 and 25 degrees C for up to 1 h resulted in changes in the rate of loss in lysosomal latency when ATP levels were adjusted from 0.0 to 5.0 mM; under these conditions as ED50 of 0.62 mM ATP was determined. The protection afforded by ATP was reversed by addition of the H+ ionophore m-chlorocarbonylcyanide phenylhydrazone (CCCP) at 10 microM to the lysosomal suspensions. A significant increase in lysosomal membrane fluidity, measured by fluorescent polarization of diphenylhexatriene, was also seen in the absence of ATP. Adenosine diphosphate (ADP) afforded significant protection only at the very highest concentration (5.0 mM); inorganic pyrophosphate (PPi) did not protect against loss of latency at any concentration. Thus ATP exerts a significant stabilizing effect on cardio(myo)cyte lysosomes in vitro and may be one of the metabolites regulating lysosomal integrity in vivo. PMID- 4014485 TI - Hemodynamic effects of arginine vasopressin in conscious water-deprived rats. AB - By means of a specific antagonist [d(CH2)5AVP] of the vasoconstrictor activity of arginine vasopressin (AVP), we studied whether the vasoconstrictor effect of AVP contributed to the blood pressure control during water deprivation in conscious rats. After 24 h of dehydration plasma AVP rose from 3.5 +/- 0.5 to 11.2 +/- 2.0 fmol/ml. Intravenous injection of 5 micrograms/kg d(CH2)5AVP reduced total peripheral resistance. Since cardiac output rose simultaneously, mean arterial blood pressure remained unchanged. In rats with sinoaortic deafferentation (SAD) 4 wk before water deprivation, d(CH2)5AVP caused a reduction of total peripheral resistance and of mean arterial pressure, whereas cardiac output remained unchanged. Consequently, mean arterial pressure fell. No hemodynamic changes were observed in hydrated control rats with and without SAD. It is concluded that the vasoconstrictor activity of AVP plays an important role in maintaining blood pressure during water deprivation in conscious rats. After AVP blockade, arterial pressure fell only in SAD rats as intact rats maintain arterial pressure via acute increase cardiac output. PMID- 4014486 TI - Relationships among arteriolar, regional, and whole organ blood flow in cremaster muscle. AB - The relationship between microvessel and tissue blood flow (BF) was determined with two different techniques during changes in local vasomotor tone in the rat cremaster muscle. Whole organ and regional BF were measured with the radioactive microsphere technique (BFms) and compared with values calculated in individual arterioles (BFc) using the dual-slit cross-correlation technique. In the muscle prepared for microcirculatory observation (i.e., dissected, surgically divided into a flattened sheet, and covered with clear plastic), resting BFms was 43 +/- 3 ml X min-1 X 100 g-1, which was significantly higher than paired BFms in the contralateral undisturbed muscle (24 +/- 7 ml X min-1 X 100 g-1). Over a range in vasomotor tone, regional BFms to the edge of the tissue, which was exposed to the trauma of the surgery, was 56 +/- 7 ml X min-1 X 100 g-1 compared with 38 +/- 5 in the less traumatized center region, a significant difference of 79 +/- 31%. There was no linear relationship between arteriolar BFc and BFms. The correlation was not improved if the factors of vessel size, vasomotor tone, animal size, or muscle size were considered. Changes in arteriolar BFc (y) overestimated changes in total tissue BFms (x) by a factor of 2 (y = 2.01x - 0.6; r = 0.86), but changes in arteriolar BFc were proportional to changes in BFms if only the center region (x) of the tissue was considered (y = 1.08x - 0.1; r = 0.84). The general implication from these results is that factors that influence perfusion heterogeneity, such as surgical trauma, should be carefully considered when correlating macro- and microcirculatory measurements of BF. PMID- 4014487 TI - Hyperresponsiveness of monoaminergic mechanisms in DOCA/NaCl hypertensive rats. AB - To examine the role of the sympathetic nervous system in the development of deoxycorticosterone acetate (DOCA)/NaCl hypertension and to test the hypothesis that the responsiveness of the sympathetic nervous system to stress is enhanced during the developmental phase of hypertension in this model before resting sympathetic activity becomes increased, DOCA/NaCl-treated rats and uninephrectomized control animals were studied after 3, 7, 14, and 28 days of treatment. Basal plasma norepinephrine and epinephrine in conscious, unrestrained resting DOCA/NaCl-treated rats were the same as in controls at 3, 7, and 14 days but were significantly elevated at 28 days of treatment. Ganglionic blockade resulted in a significantly greater decrease in mean arterial pressure in DOCA/NaCl rats than in controls at 14 and 28 days of treatment. At 14 days, DOCA/NaCl rats exhibited significantly greater increments in plasma norepinephrine and epinephrine following cold stress than did H2O controls. Basal plasma prolactin levels were elevated and release of dopamine from isolated superfused mediobasal hypothalami reduced in 28-day DOCA/NaCl hypertensive rats. These results indicate that sympathetic nervous system activity increases progressively during the development of DOCA/NaCl hypertension and that the sympathoadrenal system is hyperresponsive to environmental stress even early in the course of DOCA/NaCl treatment and suggest that hypothalamo-hypophyseal function is altered in this model of hypertension. PMID- 4014488 TI - Defining the mechanical border zone: a study in the pig heart. AB - Wall motion abnormalities can occur in nonischemic areas contiguous with ischemic myocardium. The extent of the mechanical border zone contiguous with an acute myocardial ischemic region was mapped in eight open-chest anesthetized pigs using sonomicrometer crystals implanted parallel with the visible ischemic border in the subepicardium of ischemic (IZ), proximal border (BZ1), distal border (BZ2), and remote normal (NZ) zones. Regional systolic shortening fraction was near 15%, and epicardial blood flow was approximately 1.5 ml X min-1 X g-1 in all locations before ischemia was induced. Blood flow fell to less than 0.05 ml X min-1 X g-1 and the left ventricular free wall supplied by the distal one-third of the left anterior descending artery exhibited holosystolic lengthening when the vessel was occluded. After occlusion, systolic shortening fraction was depressed by 45% in the BZ1 located 3.1 +/- 1.1 mm from the ischemic margin and by 25% in the BZ2, which was measured at 9.3 +/- 1.5 mm from the ischemic margin without significant flow reduction. The NZ, 22.3 +/- 4.6 mm from ischemic margin, was unaffected by occlusion. Computer analysis of the data shows that wall motion is depressed as far as 12 mm from the ischemic margin. This abnormal wall motion surrounding focal transmural myocardial ischemia is presumed to result from mechanical tethering. PMID- 4014489 TI - Multiple regression for physiological data analysis: the problem of multicollinearity. AB - Multiple linear regression, in which several predictor variables are related to a response variable, is a powerful statistical tool for gaining quantitative insight into complex in vivo physiological systems. For these insights to be correct, all predictor variables must be uncorrelated. However, in many physiological experiments the predictor variables cannot be precisely controlled and thus change in parallel (i.e., they are highly correlated). There is a redundancy of information about the response, a situation called multicollinearity, that leads to numerical problems in estimating the parameters in regression equations; the parameters are often of incorrect magnitude or sign or have large standard errors. Although multicollinearity can be avoided with good experimental design, not all interesting physiological questions can be studied without encountering multicollinearity. In these cases various ad hoc procedures have been proposed to mitigate multicollinearity. Although many of these procedures are controversial, they can be helpful in applying multiple linear regression to some physiological problems. PMID- 4014491 TI - Pineal gland influences period of circannual rhythms of ground squirrels. AB - Female golden-mantled ground squirrels were pinealectomized (Pinx) or Sham-Pinx at 70 days of age and maintained for more than 2 yr at 23 degrees C in a 10:14 light-dark photoperiod. Reproductive condition and body weight were recorded weekly and bi-weekly, respectively. Pinx and Sham-Pinx squirrels displayed circannual rhythms in body weight; the groups did not differ with respect to absolute magnitudes of annual peaks and troughs in body mass. The period of the circannual body weight cycle (measured peak to peak) was 27 and 58 days shorter in Pinx than in Sham-Pinx squirrels during the 1st and 2nd yr, respectively, after surgery. The onset of estrus during the second postoperative cycle occurred significantly earlier in Pinx than in Sham-Pinx squirrels. The pineal gland is not essential for the generation or expression of circannual or circadian cycles but may affect the period of some circannual rhythms. PMID- 4014490 TI - Characterization of muscles from aspartic acid obese rats. AB - This study was undertaken to determine whether changes in muscle mass, muscle fiber diameter, or shifts in fiber type occur in the aspartic acid-injected rat, an animal model of hypothalamically induced obesity. We found that diaphragm, gastrocnemius, and soleus muscle mass was 140, 149, and 171% greater, respectively, in control compared with aspartic acid-injected rats. No differences were noted in heart weights. Significant reductions in mean fiber diameter of aspartic compared with control rats were present in each skeletal muscle. Furthermore, significant size reductions were noted for each fiber type in the diaphragm, with fast-glycolytic fibers showing the greatest reduction compared with controls at both 7 and 12 mo. Fiber type composition within the diaphragm did not differ between groups but showed a change with age. These results are compared with genetic models of obesity, the Zucker rat and the ob/ob mouse, as well as the ventromedial hypothalamic lesioned rat and the gold thioglucose mouse. Based on these results, the aspartic rat appears more similar to the two genetic models of obesity and also mimics some of the effects of malnutrition in rodents. PMID- 4014492 TI - Amniotic fluid volume and fetal swallowing rate in sheep. AB - To investigate amniotic fluid (AF) dynamics and volume regulatory mechanisms, we measured the concentration of radioiodinated (125I) serum albumin (RISA), 51Cr labeled red blood cells (Cr-RBC), and 103Ru-labeled microspheres after injection into the amniotic cavity and determined AF volume and fetal swallowing rate in 22 singleton pregnant sheep. Under normal conditions 2-3 h were required for complete mixing of RISA and Cr-RBC within AF; however, when the fetus was dead only 3-5 h were required. AF volume of 17 sheep on the 5th postoperative day averaged 975 +/- 128 ml by RISA and 986 +/- 130 ml by Cr-RBC. AF volume determined with RISA and Cr-RBC correlated well. In contrast, AF volume measurement with microspheres produced erratic results. The disappearance rate of the labels in 17 ewes on the 5th postoperative day averaged 4.9 +/- 0.7%/h for RISA and 5.5 +/- 0.7 for Cr-RBC, and the calculated rates of fetal swallowing were 935 +/- 78 ml/day by RISA and 1,085 +/- 102 by Cr-RBC. In dead fetuses the disappearance rates were almost zero, suggesting that the labels disappear mainly by swallowing. Absolute volume swallowed and swallowed volume per fetal weight correlated with gestational age. AF volume correlated with fetal weight. Radiolabeled albumin or red blood cells may be used to simultaneously measure amniotic fluid volume and the rate of fetal swallowing. Furthermore it appears that fetal swallowing increases with gestational age. PMID- 4014493 TI - Monosaccharide transport into hemocytes of a sipunculan worm Themiste dyscrita. AB - The hemerythrin-containing blood cells, or hemocytes, of the sipunculan worm Themiste dyscrita were found to have a stereospecific and nonconcentrative monosaccharide transport system. The transport system transferred both D-glucose and 3-O-methyl-D-glucose (3-OMG), and transport into cells by this system was rapid, reaching 50% equilibrium in approximately 20 s at 10 degrees C with an initial concentration gradient of 0.1 mM; the contribution to total uptake by simple diffusion was very small. 3-OMG uptake showed saturation kinetics with a low half-saturation constant (Km less than or equal to 0.1 mM). The uptake of labeled 3-OMG by the hemocytes was strongly inhibited by unlabeled 3-OMG, 2-deoxy D-glucose, alpha- and beta-D-glucose, D-galactose, and D-mannose. It was moderately inhibited by D-xylose, only slightly by alpha-methyl-D-glucoside and D fructose, and uninhibited by sucrose, L-glucose, or D-sorbitol. Phloretin was more potent than phloridzin in blocking entry of 3-OMG. Cytochalasin B did not bind tightly to the T. dyscrita transporter and was not a potent inhibitor of transport; it half-maximally inhibited 3-OMG transport at 0.1 mM. Therefore, despite some differences the data suggest functional similarities in the mechanism of monosaccharide transport into blood cells of mammals and this invertebrate. PMID- 4014494 TI - Influence of age on cardiovascular reflex response in anesthetized rats. AB - To test the hypothesis that aging is associated with an altered hemodynamic response to physiological (nonpharmacological) stimuli, such as postural change and intravascular volume perturbations, we studied the adult (A, 6 mo) and senescent (S, 24 mo) Fischer 344 rat, a mammalian aging model not influenced by atherosclerosis or hypertension. Special emphasis was placed on the afferent limb of the baroreceptor reflex arc, an area not previously studied with respect to age. The base-line heart rate (HR), systemic arterial pressure (SAP), pulmonary arterial pressure (PAP), and carotid sinus nerve activity were not influenced by age. Following postural change (60 degrees upward tilt), the old animals demonstrated a greater drop in systolic pressure (-11 +/- 2, A; -21 +/- 4 mmHg, S; P less than 0.05), but there was no significant change in HR in either group. In response to a controlled withdrawal of 0.5 ml, the A had a greater reduction in systolic pressure (-29 +/- 4, A; -12 +/- 3 mmHg, S; P less than 0.01), whereas HR or PAP did not change; both groups showed a similar decrease in nerve activity. After infusions of 0.5 and 1.0 ml, the systolic and diastolic pressure changes were greater (P less than 0.02), and the changes in nerve activity appeared to be slightly more prolonged in the A compared with the S. Thus the response to changes in intravascular volume and posture are altered with age, and differences in volume-mediated venovasomotor reflex response may contribute to these age-related changes in the rat. PMID- 4014495 TI - Pulmonary vascular resistance during unilateral pulmonary arterial occlusion in ducks. AB - We measured mean pulmonary arterial pressure (Ppa) during temporary unilateral pulmonary arterial occlusion (TUPAO) in 10 ducks. Ppa increased from 11.4 +/- 0.8 mmHg during control conditions to 18.8 +/- 1.8 during TUPAO. In 5 of the 10 ducks we also measured mean left atrial pressure (Pla) and cardiac output (Q). In these ducks Ppa significantly increased with TUPAO from 13.9 +/- 0.4 to 22.0 +/- 1.2 mmHg, whereas Pla and Q did not change significantly. Pulmonary vascular resistance (PVR) increased from 10.6 +/- 1.3 to 24.1 +/- 5.3 mmHg X min X 1(-1) on TUPAO. By assuming equal vascular resistance in either lung it can be calculated that the vascular resistance in only one lung was 22.5 +/- 3.5 mmHg X min X 1(-1) during control conditions. Thus doubling flow resulted in no significant change in one lung's vascular resistance. A morphometric study of both lungs of a domestic goose that were rapidly frozen during TUPAO indicated very little compliance in pulmonary blood capillaries. The relative volume of exchange tissue occupied by blood capillaries was 0.28 in the occluded lung and 0.36 in the perfused lung. Surface-to-volume ratios of blood capillaries were 12,524 cm-1 in the occluded lung and 11,056 cm-1 in the perfused lung. We conclude that PVR in birds is relatively insensitive to changes in Q, in contrast to mammals. PMID- 4014496 TI - Food intake in diabetic rats: isolation of primary metabolic effects of fat feeding. AB - The effects of varying dietary fat content on food intake and metabolism in streptozotocin-diabetic rats were examined. The metabolic consequences of fat feeding were separated from the marked adjustments in voluntary food consumption that occur when diabetic rats are fed diets containing different amounts of fat by feeding rats a fixed ration of food in which either fats or carbohydrates were reduced by equicaloric amounts, or in which only the concentration of fat, but not other dietary nutrients, was varied systematically. Resulting changes in metabolism and subsequent ad libitum food intake on refeeding were then measured. Rats did not increase their food intake after a prior reduction in carbohydrate consumption but did so after an equicaloric reduction in fat consumption. Urinary glucose excretion during rationing was a function of carbohydrate consumption and was not predictive of changes in food intake during refeeding. The more fat that rats consumed during rationing, the higher their levels of plasma triglycerides and ketone bodies were at the time of refeeding and the less they ate when allowed to eat ad libitum. The orderly changes in food consumption and in plasma triglycerides and ketones observed with variations in fat intake suggest that the effects of fat feeding on food intake in diabetic rats are mediated through the oxidation of ingested fat. PMID- 4014497 TI - Small male body size in garter snake depends on testes. AB - In the red-sided garter snake (Thamnophis sirtalis parietalis) adult females are larger than adult males; this difference is apparent within 3 wk of birth, a time coinciding with high circulating levels of androgens. To study the ontogeny and regulation of this sexual dimorphism, male neonates were either castrated, castrated and given Silastic capsules containing testosterone or estradiol, or given a sham operation at 8, 9, or 10 wk of age. Female neonates were either given a Silastic capsule containing testosterone or dihydrotestosterone or given a sham operation at 8, 9, 10, or 14 wk of age. The sex difference in body size and growth rate in neonates was abolished by castration; the pattern of growth of castrated males was similar to sham-operated females. Androgens in the amounts administered failed to reverse the effects of castration, because castrated male and female neonates receiving exogenous androgens grew at the same rate as did sham-operated females. Males castrated as adults grow larger than adult males given a sham operation, indicating the inhibitory role of the testes on body size exists after sexual maturity. Treatment of adult males with testosterone, however, prevented the increase in body size after castration, suggesting that the mechanism regulating weight gain in the garter snake depends on gonadal androgen. PMID- 4014498 TI - Glucose and lactate kinetics in American eel Anguilla rostrata. AB - Simultaneous infusion of [6-3H]glucose and [U-14C]lactate was used to calculate the turnover rate of glucose, the irreversible replacement rate of lactate, and the rates of the exchange of carbon atoms between glucose and lactate in free swimming American eels (Anguilla rostrata) fed or food deprived for 6, 15, and 36 (maturing) mo. The mean turnover rate of glucose in fed animals averaged 1.0 mg X min-1 X 100 g-1, while the lactate irreversible replacement rate was approximately 4.0 micrograms X min-1 X 100 g-1. The conversion of 35% of lactate carbon to glucose implied a substantial Cori cycle activity, but this amounted to less than 1% of total glucose production. Food deprivation for 6 mo altered few kinetic patterns, except for an increased lactate irreversible replacement rate and a minor increase in gluconeogenesis from lactate. After a 15-mo fast, glucose turnover decreased to 0.09 +/- 0.02 mg X min-1 X 100 g-1. Plasma lactate concentrations and production rates continuously increased during the experiment. Maturing eels that had been food deprived for 36 mo maintained glucose and lactate concentrations and kinetics similar to values in animals food deprived for only 6 mo. This study stresses the importance of carbohydrate in the metabolism of this species under fed and food-deprived conditions and further supports the tolerance of Anguillid species to food deprivation. PMID- 4014499 TI - Recovery of lipid mass after removal of adipose tissue in ground squirrels. AB - Male golden-mantled ground squirrels subjected to surgical removal of substantial portions of inguinal, retroperitoneal, and epididymal adipose tissue [lipectomy (Lipx)] or to sham lipectomy (Sham) during the early prehibernatory fattening phase did not differ in body mass 4 mo later at the time of their annual body weight peaks. Body mass restoration by Lipx squirrels was achieved without compensatory increases in food intake. There was little or no regeneration of epididymal adipose tissue, complete regeneration of the retroperitoneal depot, and an increase in mass of subcutaneous fat of Lipx animals. Epididymal and retroperitoneal adipocytes were equivalent in size in Sham and Lipx squirrels; adipocytes in subcutaneous fat were 20% larger in Lipx than in Sham animals. Generation of the annual body mass cycle of this ground squirrel involves active regulation of the lipid mass. PMID- 4014500 TI - Spinal pathways mediating respiratory influences on sympathetic nerves. AB - The location of spinal pathways mediating the respiratory modulation of sympathetic nerve activity was determined. Left inferior cardiac sympathetic, phrenic, and external intercostal (T1) nerve activities were recorded in 16 alpha chloralose-anesthetized, vagotomized, paralyzed cats. Baroreceptor reflex activation of sympathetic activity was tested by bilateral carotid occlusion. Eight cats received C6-C7 level ventral spinal cord hemisections followed by cumulative lesions leading to total spinal cord transection. Eight other cats received C6-C7 level dorsolateral funiculus (DLF) lesions followed by dorsal spinal cord hemisection and subsequent spinal cord transection. The respiratory modulation of sympathetic activity was quantitatively assessed using respiration triggered computer summation of sympathetic activity. Ventral hemisection had no significant effect on the respiratory modulation of sympathetic activity or bilateral carotid occlusion responses. In contrast, bilateral DLF lesions eliminated both the respiratory modulation and bilateral carotid occlusion responses. Unilateral disruption of DLF pathways ipsilateral to the recorded sympathetic nerve indicated spinal level decussations. Thus bilaterally descending DLF pathways with spinal level decussations mediate the respiratory modulation of sympathetic activity. PMID- 4014501 TI - Psychiatric diagnosis across cultural boundaries. AB - Diagnosis across cultural boundaries has become a practical rather than an esoteric matter as migration, the number of effective psychiatric therapies, and access to psychiatric care have increased. Cross-cultural diagnosis involves such theoretical considerations as diagnostic categories, pathoplasticity of psychiatric disorder, so-called culture-bound syndromes, "emic" (intracultural) versus "etic" (cross-cultural) conceptual frameworks, and different reporting of symptoms and expression of signs from one cultural group to another. Important clinical issues include distinguishing cultural belief systems from delusions and understanding the special problems of minority, migrant, and refugee patients. PMID- 4014502 TI - Differences in nocturnal melatonin secretion between melancholic depressed patients and control subjects. AB - The authors took multiple serum samples for measurement of melatonin between 4:30 p.m. and 7:30 a.m. in seven male depressed patients with melancholia and five healthy male control subjects and found that melancholic patients had a significantly lower rise of melatonin. They also compared a second, separate group of 14 women and five men suffering from melancholic depression with seven healthy male control subjects and nine depressed women without melancholia. The melancholic patients had a significantly lower concentration of serum melatonin at 11:00 p.m. than either the control subjects or the nonmelancholic depressed patients. These findings support the possibility that the functioning of the pineal gland is altered in these patients. PMID- 4014503 TI - Bipolar I, bipolar II, and nonbipolar major depression among the relatives of affectively ill probands. AB - An earlier report described symptoms and background features in depressed probands grouped by polarity: bipolar I, bipolar II, and nonbipolar. The present study made similar comparisons among relatives with a lifetime history of major depression. The 73 relatives with bipolar II disorder had the highest rates of marital disruption, psychopathology in the previous month, nonserious suicide attempts, and nonaffective syndromes and were the youngest when first treated. PMID- 4014504 TI - Subtype stability in schizophrenia. AB - The authors examine the long-term stability of the subtypes of schizophrenia defined by four diagnostic systems. When all patients were considered, agreement between subtype assigned at index and follow-up was modest. This agreement increased considerably when only patients diagnosed as paranoid, hebephrenic, or catatonic at both index and follow-up were considered. As for individual subtypes, stability was highest for paranoid schizophrenia, intermediate for hebephrenia, and virtually absent for undifferentiated schizophrenia. The stability of paranoid schizophrenia was greatest when onset occurred after age 30. As length of follow-up increased, a larger proportion of patients were diagnosed as undifferentiated or residual. PMID- 4014505 TI - The role of the press and the medical community in the epidemic of "mysterious gas poisoning" in the Jordan West Bank. AB - In March and April 1983, an epidemic of "mysterious gas poisoning" occurred in the Jordan West Bank region, affecting more than 900 persons, predominantly schoolgirls. That both Arabs and Israelis believed there was an etiologic poisonous substance reflected their longstanding conflict. Israeli newspaper reports, opinions by Arab and Israeli physicians, and the emotional climate in Djenin Hospital contributed to the generation and propagation of this belief. The author discusses the specific difficulties he met in investigating the outbreak. PMID- 4014507 TI - The DST in psychiatric outpatients with generalized anxiety disorder, panic disorder, or primary affective disorder. AB - The authors administered the dexamethasone suppression test (DST) to outpatients, who were free from psychoactive drugs for at least 10 days before the test, with primary affective disorder (N = 60), generalized anxiety disorder (N = 26), panic disorder (N = 22), and agoraphobia with panic attacks (N = 13). With a cortisol value of 5 micrograms/dl considered nonsuppression, there were no significant differences in dexamethasone nonsuppression rates among the diagnostic groups. Scores on the Hamilton Rating Scale for Depression and a melancholia subscale were significantly higher in the depressed group than in the anxiety disorder group. The findings raise questions concerning the specificity of the DST for primary affective disorder in relationship to anxiety disorders. PMID- 4014506 TI - Antithyroid antibodies in depressed patients. AB - The presence of antithyroid (antimicrosomal and antithyroglobulin) antibodies was assessed in 45 psychiatric inpatients with prominent depressive symptoms (28 with DSM-III major depression). Nine patients (20%) had detectable titers of antithyroid antibodies, a rate considerably higher than the 5%-10% observed in the normal population. Each of these nine patients with symptomless autoimmune thyroiditis had normal baseline serum thyrotropin concentrations and normal thyroid function (as assessed by T4, T3 uptake, and free thyroxine index). These findings support the hypothesis of subtle thyroid dysfunction in a sizable sample of psychiatric inpatients with prominent depressive symptoms. PMID- 4014508 TI - Comparison of three systems for diagnosing borderline personality disorder. AB - The authors assessed three systems for diagnosing borderline personality disorder: DSM-III, the checklist criteria of Spitzer et al., and the Diagnostic Interview for Borderline Patients. In an inpatient sample of 51 patients, 43 (84%) met the criteria of at least one of these systems; analyses were carried out on 28 of these patients. Twelve (43%) of these 28 patients met criteria for all three systems, seven (25%) for two systems, and nine (32%) for only one system. Kernberg's structural criteria showed reasonable overlap with the other diagnostic criteria. Affective disorders were prominent across diagnostic measures in this sample of borderline patients. PMID- 4014509 TI - Lactate infusions in obsessive-compulsive disorder. AB - Panic attacks followed sodium lactate infusions in one of seven patients with obsessive-compulsive disorder and 26 of 48 patients with panic disorder or agoraphobia with panic attacks. This suggests that lactate-induced panic is specific to the latter groups. PMID- 4014510 TI - Plasma 10-hydroxynortriptyline and ECG changes in elderly depressed patients. AB - Among 18 elderly depressed patients given ECGs before and during nortriptyline treatment, plasma E-10-hydroxynortriptyline and the sum of E-10 hydroxynortriptyline and nortriptyline distinguished the group with conduction/repolarization effects. Plasma nortriptyline, age, drug dose, and baseline cardiovascular status did not. PMID- 4014511 TI - Treatment of PCP intoxication with verapamil. PMID- 4014512 TI - Treatment of an aggressive, compulsive adolescent with sultopride. PMID- 4014513 TI - Polydipsia in psychiatric patients. PMID- 4014514 TI - The malignant neglect of the mentally ill street people. PMID- 4014515 TI - Lithium, CNS serotonergic tone, and intoxication. PMID- 4014516 TI - Confirmation of abnormal DST results in manic patients. PMID- 4014517 TI - The placing of antifertility drugs in food supplies: one answer to our global population crisis? PMID- 4014518 TI - Do psychotherapies have specific effects? AB - The authors provide a critical review of the evidence from psychotherapy outcome research for and against the assumption that specific techniques produce specific effects. They describe the refinement in research and methodology that will be necessary to document specific effects. PMID- 4014519 TI - Fulfillment of therapeutic tasks as a precondition for acceptance in therapy. AB - Giving a patient therapeutic tasks to fulfill as a precondition for his acceptance in therapy facilitates the therapeutic process. Patients' commitment to therapy is increased, initial functioning level is raised and morale is boosted. The setting of precondition-tasks may work because of the influence of therapists' positive expectations for patients' behavior. As the patient fulfills the task his own self-efficacy expectations are enhanced. Practical aspects in the implementation of this technique are considered, and cases are described. PMID- 4014520 TI - Wife rape: barriers to identification and treatment. AB - Sexual abuse of women by husbands or long-term lovers is emerging as a significant problem in our society. Identification and treatment of this problem by the psychiatric community may be constricted by a value system that condones secrecy and tolerates abuse. This paper focuses on the significant clinical issues in such cases and offers suggestions for interventions that break down barriers between patient and therapist. PMID- 4014521 TI - I.Q. changes in young children following intensive long-term psychotherapy. AB - A review of the literature revealed only three cases of long-term psychotherapy of young children in which significant I.Q. gains were reported. A series of ten children is presented who received intensive long-term psychotherapeutic treatment and who obtained a mean I.Q. gain of 27.9 points. PMID- 4014522 TI - The effect of media involvement on transference. AB - The psychiatric literature contains contrasting opinions about the wisdom of public exposure by a therapist. This issue has become more relevant because of the recent acceptance of advertising and solicitation by professionals. Most of the current discussions focus on political and economic issues rather than the impact on the therapeutic process. This paper describes the effect of media exposure by the therapist on the transference of twenty-eight patients seen in his private practice. PMID- 4014523 TI - Man's purgative passion. AB - Overconcern with bowel function has been prevalent throughout history. Overuse of laxatives is persisting for a certain segment of the population even today. This paper attempts to put this practice into perspective by presenting a review of mankind's treatment and mistreatment of the GI system from the ancient Egyptians to modern times. PMID- 4014524 TI - Contagious hysteria in a West Bengal village. AB - This article reports on the phenomenon of contagious hysteria in a village in West Bengal. The psychosocial and psychodynamic aspects are discussed. PMID- 4014525 TI - Therapeutic processes in a Yoga Ashram. AB - Although communal and new religious groups are said to provide quasi-therapeutic experiences for relatively healthy individuals in our society, there is little information about how this occurs. This study examines the lifestyle and social structure of a yoga ashram and describes how they facilitate processes where residents learn to release and prevent stress in their lives. PMID- 4014526 TI - American Society for the Immunology of Reproduction. Abstracts from the sixth annual meeting. June 12-14, 1985, Ann Arbor, Michigan. PMID- 4014527 TI - The sensitivity of placental trophoblast cells to intraplacental and allogeneic cytotoxic lymphocytes. AB - The NK-susceptibility of trophoblast cells to allogeneic and autologous intraplacental natural killer (NK), antibody-dependent (K), and mitogen-induced cell-mediated cytotoxicity was studied, using untreated and neuraminidase-treated trophoblast cells from normal, full-term deliveries. The work was preceded by systematic studies of placental cell separation and labelling techniques, and the effects of these techniques on the NK target, K562. The results indicated that maternal NK cells are present among intraplacental lymphocytes, but that their activity is lower than that of peripheral blood lymphocytes and they are not stimulated by interferon to the same extent as peripheral blood lymphocytes (PBL). Trophoblast cells were rarely susceptible to allogeneic NK cells, with low cytotoxicity at high effector-target cell ratios in only two of five experiments. Interferon (IF)-boosted NK cells mediated some cytolysis of trophoblasts in three of four experiments, but high effector/target cell ratios were also required for the effect to be observed. The trophoblast cells could be lysed, however, by K cells and lectin-induced cytotoxicity. Removal of surface sialic acid by neuraminidase treatment of the trophoblast cells had little effect on the susceptibility of these cells to unstimulated NK cells (one of four experiments), but resulted in susceptibility to IF-boosted NK cells in four of four experiments. Normal trophoblast cells did not compete in IF-NK(K562) assays and neuraminidase-treated cells competed weakly in only one of three such experiments, indicating that the NK "target structure" is only weakly expressed on human trophoblast cells. Intraplacental lymphocytes lysed autologous trophoblast cells to a lower extent than allogeneic PBL.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4014528 TI - Head and neck injuries in college football: an eight-year analysis. AB - The present study documented head and neck injuries in a study group of 342 college football players at a single institution for a period of 8 years. All freshmen players were screened for evidence of: (1) past history of head and neck injuries, and (2) abnormalities of the cervical spine on physical examination and x-ray film. By recording all head injuries and those neck injuries with time loss, incidence rates and patterns of injury incurred in college competition were determined. A total of 175 head and neck injuries were sustained by 100 players over the 8 year period. Those players with abnormal findings on screening examination were twice as likely to have a head or neck injury at some point in their college careers as those players with a normal screening examination. The greater the degree of abnormality on freshman screening examination, the more severe the neck injury in college was likely to be. Twenty-nine percent of all players in the study group sustained a head or neck injury during their college careers. The probability of a subsequent head or neck injury escalated sharply following a single incident. The overall incidence of injury was found to have been dramatically reduced over the 8 years. Influential factors such as legislative rule changes, medical status of recruits, and general coaching philosophies are discussed with regard to injury reduction and prevention of head and neck injuries in college football. PMID- 4014529 TI - Shoulder strength following acromioclavicular injury. AB - The acromioclavicular (AC) joint enjoys the dubious distinction of being one of the few joints in the body whose total dislocation is routinely treated by simply leaving the joint dislocated. Adherents of both conservative and operative treatment have presented reasons for their viewpoints. Residual shoulder weakness has been offered as a sequela of untreated acromioclavicular injury and a reason for repairing the joint. An objective evaluation of shoulder strength would be valuable in determining the optimum treatment for this injury. The purpose of our study was to quantitate, using the Cybex II, the residual shoulder weakness following various modes of treatment. Seventeen patients with Grade III AC separations and eight patients with Grade II AC sprains were reviewed. Nine of the Grade III injuries were treated and eight nonoperatively. All Grade II injuries were treated nonsurgically. All patients were tested on the Cybex II isokinetic dynamometer at both slow and fast speeds through various ranges of motion. Grade III injuries treated nonoperatively showed no significant strength deficits. Surgically treated Grade III injuries had a significant strength deficit in vertical abduction at fast speeds (19.8%) when compared to the uninjured shoulder. Interestingly, the Grade II injuries led to a significant weakness in horizontal abduction (24.3%) at fast velocity. Evaluation of subjective results showed that Grade III injuries treated conservatively had the most pain and stiffness, despite their strong shoulders. Patients with Grade III injuries treated operatively rated their overall outcome below that of those treated conservatively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4014530 TI - A review of scaphoid fracture healing in competitive athletes. AB - A fractured scaphoid is a common disabling injury occurring in contact sports. Plaster immobilization is the most frequently used form of therapy. However, the rules governing most amateur sports do not allow an unyielding form of immobilization distal to the elbow. We describe a method of treating scaphoid fractures with custom-made Silastic (Dow Corning Wright, Arlington, TN) casts for competitive athletes. A retrospective review of 14 scaphoid fractures occurring in athletes competing in contact sports was completed to determine if effective immobilization could be maintained with this technique. The study covered a 10 year period with an average followup of 3.9 years (range 2 to 9 years). Ten of 11 middle third scaphoid fractures healed uneventfully. One nonunion occurred following a 7 week delay in diagnosis. Two of three proximal third scaphoid fractures went on to nonunion, while the third healed after a prolonged period of treatment. Our data indicate that nondisplaced middle third scaphoid fractures can be effectively immobilized for competition in contact sports with the custom made Silastic cast described. PMID- 4014531 TI - Chronic compartment syndrome: diagnosis, management, and outcomes. AB - A consecutive operative series of 100 patients with chronic compartment syndrome involving 233 compartments is reported. Seven of every eight were athletes, and runners predominated. Exercise-induced symptoms of consistently recurring tightness, aching (in some, sharp pains) in anatomically defined compartments were pathognomonic. Mean months of symptoms prior to operation was 22; median age was 26 years. Bilaterality occurred in 82. The distribution of compartments was: anterior, 39%; lateral, 12%; and posterior, 48%. Incidental compartment pressures were elevated (mean = 23 mmHg). Fasciotomy using local anesthesia was performed on 70 outpatients. At a median of 4.5 months, over 90% were cured or significantly improved in symptoms and/or function. Median time to walking unassisted was 2 days, and to resumption of conditioned running 21 days. Fasciotomy can be a safe, effective, and economical treatment for chronic compartment syndrome. PMID- 4014532 TI - Nerve injury and grades II and III ankle sprains. AB - Nerve injuries associated with inversion sprains of the ankle have been mentioned in the literature on a case presentation basis only. Sixty-six consecutive patients with Grade II (30) and Grade III (36) ankle sprains were examined by electromyography 2 weeks after injury to determine the presence and distribution of nerve injuries. Ankle active range of motion (AROM) and the number of weeks postinjury when the patient could heel/toe walk and return to full activity were also noted. Five patients (17%) with Grade II sprains had mild peroneal nerve injury and three (10%) injured the tibial nerve. Clinical measurements were normal by the end of the second week. Thirty-one patients (86%) with Grade III sprains injured their peroneal nerve, while 30 (83%) incurred posterior tibial nerve injury. Ankle AROM was impaired, and heel/toe walking (5.1 weeks) and return to full activity (5.3 weeks) were markedly prolonged. The likely cause of this injury is considered to be a mild nerve traction or a hematoma in the epineural sheath at the bifurcation of the sciatic nerve into peroneal and posterior tibial branches. This report indicates that a consistently high percentage of patients with Grade III ankle sprains sustain a significant injury to both motor nerves in the leg and that rehabilitation time is markedly prolonged. PMID- 4014533 TI - The course of partial anterior cruciate ligament ruptures. AB - In a prospective study 21 consecutive patients were followed up for an average of 6 years after partial tear of the anterior cruciate ligament (ACL) diagnosed by clinical examination and arthroscopy. The ACL tear was treated conservatively and associated lesions were sutured. At followup a knee function score was recorded. The maximum possible score was 100 points. The mean score at followup was 93 +/- 6 points. All patients were classified as good or excellent. Three knees were unstable at followup, but the score was not impaired. With a partial tear of the ACL the course is benign and the long-term result good, in contrast to total ruptures of ACLs. It is, therefore, important to make an accurate diagnosis in order to choose the proper treatment. PMID- 4014534 TI - Nontraumatic injuries in amateur long distance bicyclists. AB - All 132 participants in a 500 mile, 8 day bicycle tour were surveyed by questionnaire to characterize the demographics and bicycling experience of the riders, and to determine the frequency and severity of nontraumatic injuries they experienced. Riders who developed significant symptoms were interviewed and/or examined. Eighty-six percent of ride participants responded to the survey. The average age of the riders was 41.4 years (+/- 11.7 years). They rode an average of 95.8 miles per week on a routine basis, but the majority were new to long distance touring. Most were healthy, but 5% had serious cardiovascular disease and bicycled as part of a rehabilitation program. The most common nontraumatic injury was buttocks pain (experienced by 32.8% of riders); four had skin ulceration of the buttocks. Knee problems occurred in 20.7% of riders; patellar pain syndromes and lateral knee complaints were the most common knee problems. One cyclist withdrew from the tour because of knee pain. Neck-shoulder pain occurred in 20.4% of the riders. Groin numbness and palmar pain or paresthesias each occurred in approximately 10%. Other less common problems were foot and ankle symptoms and sunburn. PMID- 4014535 TI - A comparison of athletic mouthguard materials. AB - The development of protective mouthguards resulted from extensive injuries during participation in contact sports. This has produced a dramatic decrease in the incidence of injuries to the orofacial complex. Numerous materials and techniques have been used for mouthguard fabrication. The purpose of this investigation was to make an in vivo comparison of various thermoplastic mouthguard materials. Mouthguards were fabricated upon maxillary models of 40 members of the UCLA football team. The mouthguards were made of the following materials: poly (vinyl acetate-ethylene) copolymer clear thermoplastic; polyurethane; and laminated thermoplastic. Eleven measurements were taken for each mouthguard to demonstrate dimensional changes that occurred with wear. Statistical analyses determined differences between the types of mouthguards. The clear thermoplastic revealed less dimensional change than the polyurethane material. The laminated thermoplastic showed significantly less dimensional change than the other materials tested. PMID- 4014536 TI - Isolated posterior shoulder dislocation in a child. A case report. AB - Posterior dislocations of the shoulder are rare, and even rarer in children. The outcome depends on early recognition and treatment if normal shoulder function is to be obtained. PMID- 4014537 TI - Slipped distal femoral epiphyseal plate following closed manipulation of the knee. A case report. PMID- 4014538 TI - Megapatella following a rupture of patellar tendon. A case report. PMID- 4014539 TI - Epithelioid sarcoma. Diagnosis, prognostic indicators, and treatment. AB - A retrospective review of 241 cases of epithelioid sarcoma reaffirmed the propensity of this tumor to occur in the distal extremities of young adults. The tumor was generally firm and nontender, and involved the dermis, subcutis or deeper soft tissues, particularly fascial planes, aponeuroses, and tendon sheaths. Follow-up data, available in 202 cases (84%), showed a 77% recurrence and a 45% metastatic rate. The most common initial sites of metastasis were lymph nodes (48%) and lungs (25%). A more aggressive course was associated with a proximal or axial tumor location, increased size and depth, hemorrhage, mitotic figures, necrosis, or the presence of vascular invasion. More favorable behavior was observed when the tumor arose in younger individuals, in distal extremities, or in females between the ages of 10 and 49. (The last observation calls for further work with steroid receptors.) Radical excision or amputation still appears to be the initial treatment of choice, though adjunctive high-dose radiotherapy to the excision site may prove to be of additional value. PMID- 4014540 TI - Inverted hyperplastic polyps of the colon. AB - An unusual form of hyperplastic polyp of the colon is described in which endophytic growth can simulate adenoma or carcinoma by penetration of the muscularis mucosae and a complex epithelial growth pattern. These lesions differ clinically from exophytic hyperplastic polyps by being more frequent on the right side than in the left colon and being relatively more common in women. PMID- 4014541 TI - T-cell signet-ring cell lymphoma. A histologic, ultrastructural, and immunohistochemical study of two cases. AB - The histologic, ultrastructural, and immunologic characteristics of two signet ring cell lymphomas of T-cell derivation are presented. Histologically, both lymphomas were diffuse large cell lymphomas with many neoplastic cells containing cytoplasmic vacuoles imparting a signet-ring configuration. Ultrastructural examination revealed the vacuoles to consist of electron-lucent spaces containing variable numbers of microspherules. Immunohistochemical studies showed that both lymphomas expressed T-cell phenotypes with no reactivity with antibodies to B cell antigens. In contrast to previous reports which have shown signet-ring cell lymphomas to be invariably B-cell in derivation and usually follicular center cell type, this study demonstrates that these lymphomas may also be of T-cell origin. PMID- 4014542 TI - Neuron-specific enolase as an immunohistochemical tool for the diagnosis of Hirschsprung's disease. AB - Immunohistochemical staining of paraffin-embedded sections of rectal biopsies and of surgical specimens of the colon for neuron-specific enolase (NSE) by the peroxidase-antiperoxidase (PAP) technique greatly facilitates the diagnosis of Hirschsprung's disease. Axons were stained in normal and in aganglionic colon. The perikarya of normal ganglion cells from unaffected patients were strongly positive for NSE and were easily recognizable even when the nerve cells were immature. This technique, therefore, simplifies the task of distinguishing hypoganglionic from aganglionic colon. The hypertrophic submucosal axonal bundles characteristic of Hirschsprung's disease were also readily demonstrable. PMID- 4014543 TI - Bursa formation in secondary chondrosarcoma with intrabursal chondrosarcomatosis. AB - Osteocartilaginous exostoses (osteochondromata) are rather common bone tumors. Although most are straightforward lesions, one may occasionally encounter one of a number of well-recognized complications. In the current case, secondary malignant transformation and bursal sac formation were present. Additionally, numerous malignant chondroid nodules were shed into the attached bursa, giving rise to a large soft tissue mass, a situation which we feel is both remarkable and, to our knowledge, unique. PMID- 4014544 TI - Intraoperative biliary endoscopy (choledochoscopy) in California hospitals. PMID- 4014545 TI - Acute pancreatitis in Algeria. Report of 221 Cases. AB - A review of 221 patients operated on for acute pancreatitis during a 16 year period showed that women predominated 2:1. This is explained by the common occurrence of biliary stones in Algerian women. In more than half the patients, primary symptoms were biliary. Only 56 percent of diagnoses were established preoperatively. Acute edematous pancreatitis predominated, occurring in 58 percent, with necrotic pancreatitis occurring in 42 percent. Edematous pancreatitis was most often treated by biliary procedures and infiltration and draining of the pancreatic area. Necrotic forms were treated by necrotectomy, whereas segmental pancreatectomy was performed in seven patients. Postoperative mortality was 9.4 percent in the whole group but 37 percent in those with necrotic hemorrhagic pancreatitis. It is noteworthy that alcoholism, which is rare in Algeria, was the cause of pancreatitis in only six patients (3 percent). The main cause was biliary disease. PMID- 4014546 TI - Effect of diverting colostomy on breaking strength of anastomoses after resection of the left side of the colon. Studies in the rat. AB - In the present investigation, the effect of a proximal diverting colostomy on suture holding capacity and on anastomotic strength of the excluded left colon was studied. Suture holding capacity was increased 7 days after fecal diversion. Anastomotic strength development, however, was significantly delayed. These differences were accompanied by a diminished collagen response in the anastomotic region after fecal diversion. This might suggest impairment of healing in the excluded colon. The gross appearance of the anastomoses would, however, indicate that increased collagen formation and greater strength development in animals without colostomy is a result of more complicated healing. PMID- 4014547 TI - Nonoperative management of adult splenic injury due to blunt trauma: a warning. AB - An analysis of 11 patients with splenic injury initially receiving nonoperative treatment revealed that 73 percent subsequently required surgery for delayed hemorrhage. The influence of age and the anatomic differences between the adult's spleen and child's spleen may account for the increased incidence of delayed bleeding seen in this series. Which patients might avoid surgical intervention cannot be predicted with certainty from the mechanism of injury or the lack of early physical signs and symptoms. The corresponding medical problems that often exist with the older patient may make nonoperative management, with the inherent risk of hypotension and large transfusion requirements, inappropriate. Although not advocating immediate splenectomy, we encourage early operative intervention with splenorrhaphy. Although improved diagnostic techniques will uncover a greater incidence of splenic injury, the inability to identify the nonoperative patient remains a clinical dilemma. The true role of nonoperative management of splenic injuries in the adult and the criteria for selection need to be further defined with larger prospective series. Although this approach may be useful for some patients, its application cannot be universal, and one must be willing to accept the consequences of delayed hemorrhage. PMID- 4014548 TI - Surgical complications of peritoneal dialysis catheters. AB - Peritoneal catheters are relatively easy to insert but are associated with specific complications. Proper placement and appropriate management reduce the problems associated with these complications, reduce morbidity and mortality, and increase catheter survival. On the basis of our findings the following procedures are recommended: placement of the catheter in the operating room, use of a paramedian incision, closure of the fascia with a running nonabsorbable suture, use of small exchanges initially to allow for healing, cessation of peritoneal dialysis for a limited time when leaks occur, performance of omentectomy when necessary, repair of abdominal wall hernias preoperatively or whenever they occur, maintenance of meticulous asepsis, removal of the catheter after fungal peritonitis or multiple episodes of peritonitis with the same organism, and early operation if there is any doubt of an intraabdominal catastrophe. PMID- 4014549 TI - Management of esophageal dehiscences by an intraluminal bypass tube. An experimental study. AB - The high incidence of leaks from esophageal anastomoses and the significant morbidity resulting from spontaneous or iatrogenic perforations have prompted an experimental study involving the protection of esophageal anastomoses, dehiscences, and perforation by use of an intraluminal bypass graft. To accomplish this, a specially prepared soft tube is inserted that conducts the salivary and esophageal secretions and ingested food to the stomach, thus preventing any contact with the anastomotic site. Even in the face of surgically created gross esophageal anastomotic dehiscences and perforations, there has been a complete absence of leakage as evidenced by barium studies and by gross and microscopic examination of anastomoses and dehiscences. The technique of inserting the intraluminal bypass graft and its efficacy in protecting the esophageal anastomoses with gross dehiscences has been presented. PMID- 4014550 TI - Recurrent hyperparathyroidism due to implantation of parathyroid tissue. AB - Recurrence of hyperparathyroidism after initially successful primary operation is usually caused by inadequate resection of diseased tissue or recurrent carcinoma. Since it is known that normal parathyroid tissue may be autotransplanted into a muscle bed, it is plausible that inadvertent implantation of parathyroid tissue spilled at operation may occur. In four of 23 reoperations for hyperparathyroidism in an 11 year period, we found evidence that iatrogenic parathyroid implantation had occurred. Two of the four patients had multiple parathyroid implants in the previous operative field, and one of these patients had documented spillage of a cystic adenoma during the original operation. Another two of the four patients were found to have recurrent adenomas containing suture material at sites of previous excision of the adenomas. No patient had gross or histologic evidence of parathyroid carcinoma. We conclude that inadvertently spilled parathyroid tissue may implant in the neck or mediastinum and cause persistent or recurrent hypercalcemia. Therefore, all efforts should be made to handle the parathyroid glands only by their pedicles and not to crush, suture, or violate the capsule. Needle aspiration of parathyroid cysts could lead to implantation along the needle tract. PMID- 4014551 TI - Parotidectomy versus limited resection for benign parotid masses. AB - Parotidectomy for benign parotid masses in 86 patients has been reviewed. Morbidity, although common, was mild and transient. Recurrence and permanent facial nerve weakness did not occur in any patient with 5 to 13 year follow-up. Superficial and conservative parotidectomies remain the procedures of choice for most benign tumor masses. PMID- 4014552 TI - Treatment of necrotizing soft tissue infections. The need for a new approach. AB - Necrotizing soft tissue infections are classified by the type of infecting organism, the presenting clinical picture, and the treatment required. However, reliance on this schema is impractical since it often leads to an inordinate delay in appropriate surgical therapy with an unwarranted loss of a limb or life. Since 1958, 21 patients were treated at the UCLA Medical Center with necrotizing soft tissue infections. Unifocal ulcerations and nonspreading infections were excluded. Of the 21 patients, the initial classification of the infections included necrotizing fasciitis in 38 percent, clostridial gangrene in 38 percent, bacterial synergistic gangrene in 19 percent, and streptococcal hemolytic gangrene in 5 percent. Diabetes or evidence of immunosuppression was found in 71 percent of the patients. The course could be traced to either a perforated viscus in 43 percent or a traumatic injury in 43 percent. No single clinical sign, including tissue gas, was diagnostic for a specific type of necrotizing soft tissue infection. Culture revealed a polymicrobial flora in 76 percent. Overall mortality was 52 percent and the amputation rate was 36 percent. Mean time to appropriate surgical therapy was 1.9 days. Operations performed more than 24 hours after recognition of infection resulted in a 70 percent mortality versus a 36 percent mortality when operations were performed less than 24 hours after recognition. A lesser operation to conserve tissue resulted in a 71 percent mortality versus a 43 percent mortality with initial radical surgery which encompassed all devitalized tissue. Based on these data, we conclude that classification of necrotizing soft tissue infections should be simplified to clostridial and nonclostridial infections. Radical operative debridement, regardless of tissue loss, should be carried out immediately after fluid resuscitation, and antibiotic coverage must be broad spectrum from the time of onset due to the polymicrobial nature of these infections. PMID- 4014553 TI - Surgical treatment of high gastric ulcer. AB - The purpose of this study has been to review the late results of surgical treatment of 244 patients with endoscopically proved benign chronic gastric ulcer located 5 cm or less from the cardia. In five patients, a total gastrectomy with esophagojejunostomy was performed. Proximal gastrectomy was used in 3 patients, mesogastrectomy in 5 patients, a partial Schoemaker's procedure in 73 patients, Pauchet's procedure in 70 patients, and Csendes' procedure in 23 patients. Nonresective procedures were employed in 67 patients and included the Kelling Madlener procedure in 23 patients, pyloroplasty alone in 10 patients, gastrojejunostomy alone in 4 patients, local or wedge excision of the ulcer in 9 patients, and vagotomy and pyloroplasty in 21 patients. The follow-up evaluation was performed in 91 percent of the patients (mean 9 years postoperatively, range 5 to 15 years), with emptying endoscopy in all nonresected patients. A high mortality was observed after total or proximal gastrectomy, as well as after nonresective procedures. After the other resective techniques, low postoperative morbidity and mortality were observed. No recurrent ulcer was seen after the resective procedures. Based on these results, we propose that when the ulcer is located 5 cm below the cardia, Schoemaker's or Pauchet's procedure should be performed; if the ulcer is located 2 cm or less from the cardia, Csendes' procedure or the Kelling-Madlener procedure should be employed. PMID- 4014554 TI - Surgical management of gastric adenocarcinoma. AB - This paper has analyzed the results of surgical management of 196 patients with gastric carcinoma treated from 1958 through 1982 at the Brigham and Women's Hospital in Boston and compares the experience during this time period with that of the previous 45 years. Surgical technique, operative mortality and complications, and 5 year survival were recorded. The resectability rate of the tumor in patients explored was 78.1 percent, and the 5 year survival rate for all 153 gastrectomies was 24.9 percent (36.2 percent for curative gastrectomy and 8.6 percent for palliative gastrectomy). Chronologic comparison over the years showed a decrease in the incidence of cancer of the stomach over the past 65 years, a steady increase in the 5 year absolute survival of patients with gastric carcinoma, and a significant decrease in the operative mortality and an increase in the 5 year survival after subtotal gastrectomy. PMID- 4014555 TI - Distribution of colorectal cancer in patients with and without ulcerative colitis. AB - A comparison of the anatomic distribution of colorectal cancer in patients with and without CUC is difficult because of the unequal number of patients in each group and the changing epidemiologic parameters of colorectal cancer in general. In the present study, the distribution of colorectal tumors in patients with and without CUC was compared over two different time periods at a single hospital. In the early time period (1960 to 1975), there was a significantly higher percentage of proximal tumors in the group with cancer and CUC compared to the group with cancer alone. In the most recent time period (1975 to 1981), there was no difference in distribution of colorectal cancer regardless of whether the patient had CUC or not. We believe that the increased percentage of proximal tumors in patients with colorectal cancers and no CUC that has occurred in recent years has led to the present findings of a similar distribution of tumors in patients with and without CUC. PMID- 4014556 TI - Serendipitous adrenal masses: prevalence, significance, and management. AB - Over a 2 year period, 63 of 1,459 patients examined by computerized tomography were found to have adrenal masses. In 19 patients (1.3 percent of patients examined and 30 percent of patients with adrenal masses), they were unexpected and did not give rise to symptoms or signs. Three patients were explored. Two of the patients had adrenocortical adenomas and a third, a ganglioneuroma. Adrenal function tests were performed in 14 patients and showed evidence of Cushing's syndrome in 1 patients and revealed no abnormalities in 13. The lesions in 10 of 11 nonsurgical patients followed by computerized tomography for 11 to 36 months showed no change. One lesion became significantly smaller. In a review of 988 autopsy reports, grossly visible adrenal masses were present in 73 patients (7.3 percent), including 19 adrenocortical adenomas (1.9 percent) and 50 metastases (5 percent). We conclude that serendipitous adrenal masses are usually small, nonfunctioning, and benign, the most common lesion being adrenocortical adenoma. A protocol has been suggested for management to identify the minority of patients with functioning or malignant lesions and to avoid unnecessary surgery in the others who have benign disease. PMID- 4014557 TI - Innovations in skin suture removal. AB - A cutting forceps and suture removal scissors have been specially designed for removal of percutaneous sutures. Our clinical experience with these instruments indicate that they facilitate removal of percutaneous sutures in the surgical patient. PMID- 4014558 TI - The fuzzy foreign body fragment: a subtle roentgenographic clue to mediastinal vascular injury. AB - Foreign body injury to mediastinal vascular structures may be present in clinically stable patients who have sustained thoracic trauma. Angiography may occasionally fail to demonstrate such an injury which may lead to delay in surgical management. A subtle roentgenographic finding consisting of a fuzzy metallic fragment contiguous with the mediastinum on admission chest films suggested vascular injury in two patients and prompted surgical exploration. Despite preoperative hemodynamic stability and normal angiograms, major transmural injuries to the pulmonary artery and aorta were encountered in these two patients and were managed successfully. PMID- 4014559 TI - Congenital duplication of the gallbladder associated with an anomalous right hepatic artery. AB - A case report describing the incidental finding of a double gallbladder associated with an anomalous anteriorly displaced right hepatic artery has been presented. The literature has also been reviewed and the appropriate surgical intervention for supranumerary gallbladder suggested. PMID- 4014560 TI - Familial visceral myopathy: the role of surgery. AB - Familial visceral myopathy is a form of chronic intestinal pseudoobstruction in which fibrosis of the smooth muscle of the alimentary tract causes protean symptoms of disordered visceral motility. Based on our 8 year observation of six members of one family with familial visceral myopathy and review of the few well documented case reports of this disease, we have confirmed a role for surgeons in tissue diagnosis, case identification, and palliation of incapacitating symptoms of familial visceral myopathy after obtaining dynamic radiographic assessment of the entire alimentary canal. Because the duodenum and colon are the usual sources of major dysmotility symptoms, patients incapacitated by duodenal or colonic pseudoobstruction may benefit from bypass or resective operations. PMID- 4014561 TI - Limb-sparing surgery for extremity sarcomas after preoperative intraarterial doxorubicin and radiation therapy. AB - Complete local control of 25 extremity bone and soft tissue sarcomas was obtained by combined preoperative intraarterial doxorubicin and radiation therapy, followed by limb-sparing resection with reconstruction and adjuvant chemotherapy. At a 32 month median follow-up, there are no local tumor recurrences. Functional limbs were salvaged in 21 patients (84 percent). Fifteen patients (60 percent) were continuously disease-free and overall survival was 80 percent. After the extensive combined modality therapy, extremity complications, including delays in wound healing, occurred in 10 patients. Nevertheless, most complications were resolved with salvage of functional limbs. These results support an aggressive multimodality limb-sparing approach to high-grade extremity sarcomas. PMID- 4014562 TI - Cancer of the distal esophagus and cardia: preoperative irradiation prolongs survival. AB - Ninety-five patients with carcinoma of the esophagus and gastric cardia seen between 1979 and 1984 were managed in one of four ways: radiotherapy alone (6,000 rads), esophagogastrectomy alone, preoperative radiotherapy (4,000 rads over 4 weeks) followed by esophagogastrectomy, or no definitive treatment for patients with advanced disease. Patients who receive radiotherapy alone or no definitive therapy were considered unfit for operation; however, those patients who had operation only were equivalent with regard to histologic stage and risk to patients who received preoperative radiotherapy and surgery. Patients who received no definitive therapy died within 1 year, with a mean survival of 3.7 months. The mean survival for patients who received radiotherapy only was 8.3 months; for those who had surgery alone, 13 months; and for those who had preoperative radiotherapy, 24 months. Patients who received preoperative radiotherapy had significantly longer survival times when followed 12, 15, and 18 months postoperatively. Preoperative radiotherapy did not improve overall resectability, and postoperative mortality was similar in the two surgical groups. In comparable patients treated by esophagogastrectomy, preoperative irradiation prolonged the disease-free survival time and is advocated for all surgical candidates. PMID- 4014563 TI - Pancreatic abscess: impact of computerized tomography on early diagnosis and surgery. AB - Pancreatic abscess continues to be a lethal complication of acute pancreatitis, with mortality rates of 40 percent in recent surgical series. A major factor contributing to this high mortality has been delay in diagnosis. When combined with diagnostic needle aspiration, computerized tomographic scanning has greatly enhanced the early detection of pancreatic abscesses. In a 4 year period at our institutions, 21 patients with proved pancreatic abscesses were evaluated early in their clinical course by computerized tomography. On follow-up ranging from 7 months to 3 1/2 years, there were only four deaths for a mortality rate of 19 percent. Many of the surviving patients had a long and protracted clinical course (mean length of hospitalization was 56 days) and reoperation for recurrent abscess or gastrointestinal complications was required in eight patients (38 percent). Computerized tomography proved to be of considerable value in localizing the site of de novo or recurrent pancreatic abscess and in detecting postoperative complications. An aggressive approach encompassing early computerized tomographic scanning with diagnostic needle aspiration appears to be a factor in the improved survival rate of these patients. PMID- 4014564 TI - Management of injuries of the thoracic and abdominal aorta. AB - Thirty-five patients had surgery for injuries of the aorta at the Los Angeles County-USC Medical Center over a 4 1/2 year period. There were 27 survivors. The principles of management were to operate without delay if there was evidence of continued bleeding after initial fluid replacement as occurred in 11 patients. For the 24 patients who became stable after initial resuscitation, a more deliberate plan of management was used. Blood pressure was carefully monitored and controlled to avoid hypertension. Priorities for associated injuries were established and in several cases, they took treatment precedence over the aortic injury. Delay was sometimes necessary to utilize the more experienced personnel. In no instance did a stabilized patient hemorrhage during the delay. The most common injury seen was a blunt disruption of the proximal descending aorta. The details of the operative technique for this injury have been reported herein, along with a justification for not using either pump bypass or shunt to perfuse the distal aorta during the period of aortic cross-clamping. PMID- 4014565 TI - Choledochal cysts: results of primary surgery and need for reoperation in young patients. AB - The UCLA Medical Center experience in the surgical treatment of 23 young patients with choledochal cysts over a 28 year period has been reviewed. All patients had saccular or fusiform extrahepatic cysts, and one patient also had a diverticular cyst. Eleven patients had no intrahepatic dilatation, whereas 9 had cylindrical and 3 cystic intrahepatic dilatation. There were 39 operations for biliary drainage performed: 17 Roux-Y choledochojejunostomies, 7 choledochoduodenostomies, 7 excisions, and 8 miscellaneous procedures. The morbidity for initial operations was 17 percent and for reoperations, 31 percent. Biliary calculi were found after 2 of 23 primary operations (9 percent) and 6 of 16 reoperations (37.5 percent). All developed while enteric drainage was present and were primary bile duct stones. No reoperation was necessary after cyst excision. An intrahepatic cholangiocarcinoma developed in one patient treated with enteric drainage. Three of 10 patients who did not undergo cholecystectomy at their initial operation later required laparotomy for cholecystectomy alone. We recommend cholecystectomy and cyst excision when technically feasible for primary operative treatment of choledochal cysts. PMID- 4014566 TI - Lumbar sympathectomy for lower extremity vasospasm. AB - Ten patients, 8 female and 2 male, with refractory episodic lower extremity vasospasm were encountered during a 15 year period in which over 600 patients with upper extremity vasospasm were studied. Seven patients had associated upper extremity vasospasm. No patient had evidence of autoimmune disease. Lower extremity reserpine Bier block produced symptomatic relief for 1 to 3 days in all patients in whom it was used. Oral medications were ineffectual. A diagnostic toe photoplethysmographic pattern was noted in these patients, consisting of a normally pulsatile tracing after warming and a flat, nonpulsatile or minimally pulsatile tracing after cooling. Each patient underwent lumbar sympathectomy. During follow-up, which averaged 4 years, each patient remained free of episodic vasospasm on the side of surgery. We conclude that lumbar sympathectomy is an effective and durable treatment for lower extremity vasospasm. PMID- 4014567 TI - Carotid endarterectomy in the awake patient. AB - The advantages of performing carotid endarterectomy in the awake patient have been presented based on a 13 year experience. Anesthesia consisted of either local infiltration of local lidocaine or regional neck block supplemented by intravenous sedation. The principal advantages of the technique are that it is the only exact method of assessing the need for an intraluminal shunt by neurologic assessment of the awake patient during trial carotid cross-clamping, and the elimination of general anesthesia allows carotid endarterectomy to be safely performed on patients with advanced inoperable coronary artery disease and in those with chronic obstructive pulmonary disease. One hundred consecutive carotid endarterectomies have been reported with one late death and one mild, permanent neurologic deficit. These results support the belief that carotid endarterectomy can be performed with very low morbidity and mortality rates by operating on the awake patient. PMID- 4014568 TI - Alkaline reflux gastritis and the effect of biliary diversion on gastric emptying of solid food. AB - We prospectively studied 15 consecutive patients treated for alkaline reflux gastritis to determine the gastric motility pattern associated with this disease and the effects of Roux-Y gastrojejunostomy on gastric emptying. Eleven patients had previous antrectomies (the Billroth I procedure in 4 and the Billroth II procedure in 7), and 4 had previous cholecystectomies. Gastric emptying was measured before and after Roux-Y reconstruction by computer analysis of data from a scintillation camera using technetium 99m tagged chicken liver mixed with beef stew. Gastric emptying was also measured in another 10 patients who had previous Roux-Y gastrojejunostomies and were thought from clinical findings to have gastroparesis. In the patients with alkaline gastritis, before surgery gastric emptying was normal in 25 percent, rapid in 45 percent, and delayed in 30 percent. After Roux-Y reconstruction, the rate of gastric emptying increased in 25 percent of patients, decreased in 45 percent, and did not change in 30 percent. Gastric bezoars developed in half of the patients whose gastric emptying decreased after surgery. There were no technical features of the operations nor mechanical abnormalities of the reconstructions that characterized the patients whose gastric emptying slowed postoperatively. Forty percent of the patients studied only after Roux-Y reconstruction had rapid gastric emptying, 30 percent had normal gastric emptying, and 30 percent had delayed gastric emptying. These data show that patients with alkaline reflux gastritis do not have a single pattern of gastric emptying, and Roux-Y reconstruction has no consistent effect on gastric emptying. PMID- 4014569 TI - The surgeon and the cost of medical care. PMID- 4014570 TI - Value of therapeutic hyperthermic limb perfusion in advanced recurrent melanoma of the lower extremity. AB - Twenty-six patients with advanced melanoma metastases confined to the lower extremity underwent 28 therapeutic limb perfusions without a major complication or treatment-related death. A complete response to treatment occurred in 21 patients (81 percent). Of 16 patients, response persisted until death in 13 and was noted at 75, 87, and 96 months follow-up in 3. In five patients, response lasted a median of 5 months (range 3 to 14 months), and repeat perfusion in two of these patients was not beneficial. Unfortunately, despite locoregional disease control, most patients died from distant metastases at a median of 15 months after treatment. In fact, regardless of response to perfusion, the 3 year survival rate of patients with advanced metastatic melanoma of the extremity was only 25 percent or less. Thus, although limb perfusion can be a safe and highly effective means of achieving locoregional disease control, there appears to be little survival benefit. Therefore, perfusion should be reserved for palliative treatment of selected patients with locally advanced melanoma. PMID- 4014571 TI - Aortic and peripheral prosthetic graft infection: differential management and causes of mortality. AB - This report of 25 patients with prosthetic graft infection has compared the diagnosis, management, and outcome in 14 patients with infected aortic grafts with 11 patients with infected peripheral grafts (two axillofemorofemoral, five femorofemoral, five femoropopliteal, and one femoral interposition). Peripheral graft infection had a significantly shorter interval to diagnosis compared with aortic graft infection. Total graft removal combined with either autogenous revascularization or extraanatomic bypass using prosthetic graft was performed in all 14 patients with infected aortic grafts. Management of peripheral graft infection consisted of total graft removal in eight patients (four with autogenous revascularization and two with amputation) and partial graft removal in three patients (two with amputation). Mortality and amputation rates for infected aortic grafts were 43 percent and 25 percent, respectively compared with 36 percent and 27 percent for infected peripheral grafts. Recommendations for management of the infected aortic prosthetic graft include total graft removal, but methods and timing of revascularization are dependent on the specific features of the individual case. However, preferred management for the infected peripheral prosthetic graft includes total graft removal and, if indicated, revascularization using autogenous tissue. PMID- 4014572 TI - External carotid artery reconstruction: its role in the treatment of cerebral ischemia. AB - Twenty-one patients who underwent 22 external carotid artery reconstructions for cerebral ischemia were reviewed. Ten patients had amaurosis fugax, 9 had hemispheric ischemia, and 2 were asymptomatic. With the exception of one patient, all had ipsilateral internal carotid artery occlusion and either external carotid stenosis or a cul-de-sac of the occluded internal carotid artery. Six patients had ipsilateral common carotid occlusions. The operative technique has been presented. There were no operative strokes or new neurologic deficits. All patients were relieved of symptoms. Patients were followed a mean of 32 months. During follow-up, 3 ipsilateral transient ischemic attacks occurred during the first 3 months. Four strokes occurred (one ipsilateral and three contralateral) from 4 to 33 months postoperatively. Ipsilateral stroke rate by life table analysis was 1 percent per year. These data suggest that external carotid artery reconstruction is a safe, effective, and durable therapeutic alternative for management of patients with cerebral ischemia and an ipsilateral occluded internal carotid artery. External carotid endarterectomy eliminates a potential source of emboli and increases cerebral perfusion. Because of the increase in cerebral blood flow, subsequent extracranial-to-intracranial bypass may be unnecessary. PMID- 4014573 TI - Influence of age on mortality of colon surgery. AB - The geriatric population continues to grow and surgical decision making is often confused by the effect of aging. This study is part of an ongoing effort to determine surgical risk in the elderly population and to identify the significant factors affecting outcomes which could be used to plan surgical procedures. Records of 163 patients over 70 years of age with elective or emergency surgery (133 patients and 30 patients, respectively) were reviewed. There were 17 deaths. All deaths in a cohort of patients under 70 were examined as well. Ninety-five variables were explored to seek differences between groups. The patients who died, independent of age, were similar. Patients over 70 years of age who died differed from the survivors in many ways, both physiologically and in terms of disease state. Survivors were younger; did not have congestive heart failure; had better hepatic, renal, and pulmonary function; less extensive involvement if malignant disease was present; and fewer postoperative complications. If these factors were removed and only apparently normal physiologic characteristics considered, there were no differences in mortality between the patients over 70 years of age and younger patients. Age was less of a factor than physiologic status. PMID- 4014574 TI - Aggressive approach to the extremity damaged by electric current. AB - Electrical current injuries involving the extremities occurred in 41 of 75 patients with electrical burns admitted to the Oregon Burn Center over an 11 year period. Based solely on physical findings, the muscle compartments of 27 limbs in 14 patients were promptly explored, decompressed, and debrided of necrotic tissue on admission. This resulted in the salvage of 10 useful extremities. Major amputation of 11 extremities was carried out during initial surgery. No extremity needing exploration was overlooked. After exploration and fasciotomy, exposed tissues were protected with biologic dressings until repeated explorations and debridements demonstrated the absence of necrotic tissues and closure could be accomplished. The use of both local and free flaps was helpful in closing the wounds. No evidence or renal failure and no deaths attributable to retained necrotic tissue occurred. PMID- 4014575 TI - Lung abscess: a changing pattern of the disease. AB - Alcoholic stupor with aspiration has been the most commonly recognized cause of lung abscess. Eighty-nine patients treated for lung abscess in a large community hospital from 1968 through 1982 have been described. Forty-six percent of these patients were 60 to 80 years of age. The most common predisposing factors included pneumonia, immunosuppression steroid therapy, carcinoma at a distant site, alcoholism, and lung cancer. Surgical therapy was employed in 23 patients when there was suspicion of cancer and failure to improve with medical management. Fifty-seven percent of patients were either cured or improved at the time of discharge. Twenty-nine percent died from other causes during hospitalization, and 9 percent died as a direct result of the abscess. Thus, the patients encountered in the community hospital setting tended to be older and had a wide variety of illnesses that precipitated the development of lung abscesses. PMID- 4014576 TI - Inner ear immunology. AB - Previously the authors proposed that the perilymphatic inner ear immune system is independent of that of the cerebrospinal fluid. In the present study, the effect of dilatation of blood vessels surrounding the cochlea of chinchillas on the transfer of serum antibodies to the perilymph was tested. The possibility of local production of antibodies in the perilymphatic space was also investigated by antigen introduction into the inner ear through the facial nerve canal. The dilatation of blood vessels accelerated the transfer of serum antibodies to the perilymph, even though this transfer activity was limited. Results of the study, showing the effect of antibody production in the perilymphatic space upon introduction of antigen into the inner ear through the facial nerve canal, would deny local antibody production in the inner ear, particularly in the perilymphatic space. PMID- 4014577 TI - Oxygen consumption of middle ear and peripheral blood neutrophils in acute suppurative otitis media. AB - Using an oxygen electrode, oxygen consumption has been measured in peripheral blood neutrophils and the corresponding middle ear fluid neutrophils of 26 patients with acute suppurative otitis media. The data suggest that the middle ear fluid neutrophil is functional and is capable of producing an adequate oxygen burst in response to membrane stimulation by opsonized zymosan particles. Some middle ear neutrophils are actually capable of producing a greater respiratory burst than their counterparts in the peripheral blood. However, middle ear neutrophils do not show the increased metabolic activity at 40 degrees C, which blood neutrophils regularly displayed compared with tests performed at 37 degrees C. It is believed that this temperature (40 degrees C) is more physiological during infection and might explain why middle ear neutrophils may not always be capable of destroying bacteria, even though they are present in adequate numbers in the middle ear fluid in some cases of acute suppurative otitis media. Further studies are needed to determine the nature of the defect(s) present in middle ear neutrophil at 40 degrees C. PMID- 4014578 TI - Color electromyographic topographic analysis of facial movements. AB - To determine the precise amount of facial function present in patients with facial palsy, color electromyographic (EMG) topograms of the facial movements were made using a computerized system, newly designed and manufactured by the authors. During mimetic movements, such as wrinkling the forehead, closing the eyes, blinking, grinning, and blowing out the cheeks, EMGs from 16 monopolar disk electrodes were concurrently recorded from the frontalis, orbicularis oculi, and orbicularis oris muscles on both sides. The amplitude values of the integrated EMG spikes from each electrode were calculated by an interpolation formula in the computer, and the color topographic figures derived from these calculations were displayed on a ten-color computer monitor. The colors ranged from blue to dark red, and they were related to the amount of muscular activity. This technique was applied to patients with facial palsy to document their degree of mimetic movement loss and the time course of the palsy evolution. The results obtained were reliable and reproducible, and the technique made it easy to quantify the loss of mimetic movements in patients with facial palsy. PMID- 4014579 TI - The eustachian tube midportion in infants. AB - The eustachian tube midportion in infants and children was measured in 44 eustachian tubes from normal temporal bones and 11 eustachian tubes from temporal bones harboring acute otitis media. The temporal bones were serially sectioned, and the lumina of the eustachian tubes' midportions were measured with the aid of a grid mounted on a microscope. These measurements showed that the eustachian tube lumen grows to a small degree with age. Each age group showed a considerable variation in the range of the luminal area compatible with natural biologic distribution. No statistically significant difference was found in the sizes of the midportions of the eustachian tube lumina from temporal bones that harbored acute otitis media when compared with the lumina of the eustachian tube midportions from normal ears. PMID- 4014580 TI - Pupillary dynamics in patients with Meniere's disease. AB - A newly devised pupillograph that can record the pupillary responses of both eyes simultaneously in a supine subject is described. Three patients with Meniere's disease in the attack and quasiattack stages showed a similar abnormality of pupillary light contraction on the affected side, compared with the unaffected side, that disappeared in the interval stage. These results are discussed in regard to the possible cause of Meniere's disease. PMID- 4014581 TI - Norepinephrine in cochlear microcirculation of guinea pigs. AB - The blood flow in the radiating arteriole through a small cochlear fenestra was recorded with motion pictures in anesthetized guinea pigs, before and after norepinephrine injection into the ipsilateral carotid artery. The flow velocity was determined by measuring the displacement of plasma space running through the radiating arteriole per second. Norepinephrine injection of 0.01 and 0.15 mg/kg increased both flow velocity and arterial blood pressure. The flow velocity increase related directly to the increase in arterial blood pressure. However, a larger norepinephrine dose (1.2 and 2.5 mg/kg) led to transient cessation in flow, which was independent of the blood pressure increase. Dilatation of vessel diameter was always observed with the rise in blood pressure, irrespective of norepinephrine doses. When blood flow in the radiating arteriole stopped after a large norepinephrine injection, the arteriole's vascular lumen was completely obstructed by the aggregated red blood cells. These results suggested that cochlear microcirculation is disturbed by microemboli formed by norepinephrine induced platelet hyperaggregation. PMID- 4014582 TI - Prevention and cure of some effects of auditory deprivation. PMID- 4014583 TI - Tympanic membrane changes resulting from different methods of transmyringeal middle ear ventilation. AB - This experimental study was designed to evaluate the morphologic changes of the tympanic membrane in the rat after different methods of transmyringeal ventilation. Artificial ventilation was obtained in two principal ways, either by making tympanic membrane perforations with delayed healing or by inserting a tympanostomy tube. Perforations occupying the upper rear quadrant of the tympanic membrane were made by diathermy or by a carbon dioxide laser with healing times of 12 to 15 days and 18 to 21 days, respectively. Compared with the healing times of perforations made by lancet (9 to 11 days), the healing pattern was considerably delayed. The structural changes of the healed tympanic membrane were minimal, but the connective tissue remained thickened for several months. Repeated insertion of tympanostomy tubes caused a remarkable thickening (30-fold) of the tubulated quadrants. The thickened tympanic membranes were characterized by a hyperplastic, dense connective tissue containing sclerotic plaques. Similar changes, though less pronounced, were also seen after reiterated myringotomies without tube insertion. PMID- 4014584 TI - [Clinical thinking in modern obstetrics. I. The gnoseological clinical aspect]. PMID- 4014585 TI - [Concentration of magnesium and calcium electrolytes in the last trimester of normal pregnancy and in fetal hypotrophy]. PMID- 4014586 TI - [Our treatment experience in late pregnancy toxicoses using bed rest]. PMID- 4014587 TI - [Our treatment experience in premature labor using bed rest]. PMID- 4014588 TI - [Dexamethasone induction and preparation for labor in prolonged pregnancy]. PMID- 4014589 TI - [Dynamic changes in the mean values of systolic blood pressure during tocolysis with the beta-adrenomimetic Pre-par]. PMID- 4014590 TI - [Comparative evaluation of inhalation anesthetics in cesarean section]. PMID- 4014591 TI - [Hemodynamic changes during epidural anesthesia for cesarean section]. PMID- 4014592 TI - [Treatment of hormonal sterility in the family]. PMID- 4014593 TI - [Characteristics of bacterial infection in chronic nonspecific epididymitis]. PMID- 4014594 TI - [Our cerclage method in congenital uterine anomalies]. PMID- 4014595 TI - [A rare case of combined uterine and extrauterine pregnancy and the birth of live and viable fetuses]. PMID- 4014596 TI - [Case of posthemorrhagic nonhemolytic anemia in a newborn infant]. PMID- 4014597 TI - [A rarely encountered formation simulating an ovarian tumor]. PMID- 4014598 TI - [Thyroid functional characteristics in normal pregnancy]. PMID- 4014599 TI - [Passive smoking among pregnant women and its effect on the weight and growth of the newborn infant]. PMID- 4014600 TI - [Monitoring changes in the reactivity of the premature fetus during tocolysis with the beta-adrenomimetics Partusisten and Pre-par]. PMID- 4014601 TI - [Spontaneous delivery of a live giant fetus weighing 6750 g]. PMID- 4014602 TI - [Etiology of a clavicular fracture due to the birth process]. PMID- 4014603 TI - [Anesthesia of labor by epidural analgesia. I. The effect and impact on the mother and labor activity]. PMID- 4014604 TI - [Anesthesia induction in cesarean section. A comparison of thiopental with althesin]. PMID- 4014605 TI - [Beta therapy in treating leukoplakia vulvae]. PMID- 4014606 TI - [Rupture of an ovarian cyst during the puerperium--its diagnosis and management]. PMID- 4014607 TI - Diagnosis of atypical patients with lipid storage diseases. PMID- 4014608 TI - Practical problems of therapeutic drug monitoring of anticonvulsants. PMID- 4014609 TI - Proceedings of the 26th annual meeting of the Japanese Society of Child Neurology. Osaka, June 21-23, 1984. Abstracts. PMID- 4014610 TI - [Bronchoalveolar lavage as a diagnostic method in intensive therapy]. AB - Bronchoalveolar lavage is presented as a standardised diagnostic method in the clarification of interstitial pulmonary changes in the acute respiratory distress syndrome (ARDS). Its justification is based on the fact that changes in lung biopsies are reflected by early changes in the composition of the rinse and in the ability of the cellular components to function properly, independent of the origin of the immunological processes in ARDS. Pulmonary function is not adversely affected by the procedure provided it is carried out "lege artis". We hope that it will be possible in future to achieve early detection of a developing progressive failure of pulmonary function, by employing early markers. The procedure also allows continual follow-up of the success of an initiated therapy. PMID- 4014611 TI - [Animal experiment studies on the hemodynamic effect of adrenaline following intravenous and endobronchial administration]. AB - The objective of this study was to find a dosage of endobronchially administered epinephrine with haemodynamic effects comparable to those after intravenous injection and therefore useful in cardiopulmonary resuscitation without an intravenous line. We found that 100 micrograms/kg epinephrine given endobronchially was almost as effective as an intravenous dose of 10 micrograms/kg concerning onset (10 seconds after intravenous injection, 15 seconds after endobronchial instillation) and maximum drug effect but with a remarkable prolongation of drug action. The instillation of 250 micrograms/kg epinephrine produced no significant increase in haemodynamic response. It was concluded, that the endobronchial instillation of epinephrine--in adequate dosage -is very useful in CPR without an intravenous line. PMID- 4014612 TI - [The situation on relatives in the intensive care unit]. AB - Up to now there are almost no investigations on the situation of relatives of ICU patients. Therefore a study was designed into the impressions left on relatives by intensive care treatment in their next of kin. A questionnaire including 46 items was developed which mainly refers to the following topics: first contact with the ICU, experience with the situation in the ICU, information given on the patient's state, psychosocial assistance, evaluation of experiences made in the ICU. The questionnaire was sent to 210 relatives of former long-term intensive care patients; 57 completed forms could be evaluated. It can be demonstrated that the first contact with the ICU is characterised by the concern for the patient's actual state of disease so that previous information about the ICU and on the patient's condition are considered helpful. The contact with the intensive care patient seems to be most impressive for all relatives. It creates feelings of uneasiness, compassion and despair. The relatives of moribund patients additionally show feelings of mourning. The request for information mainly refers to the patient's present state. The technical equipment of the ICU represents a reassuring factor to most of the relatives; likewise the smallest number of them feels disturbed by witnessing therapeutical measures. The relation to the medical and nursing staff is described as positive, especially by relatives of surviving patients. In retrospect the relatives--like the former ICU patients--hold a positive view of the intensive care unit. The reasons are discussed. PMID- 4014613 TI - Local and regional anaesthesia in children. PMID- 4014614 TI - Sciatic nerve block for children. Sciatic nerve block by the anterior approach for postoperative pain relief. AB - This study aimed to establish whether it was practical to perform sciatic nerve block by the anterior approach in a group of children of different ages and weights. A total of 82 blocks were performed of which 78 (95.2%) were judged to have been successful. The technique of the block differed slightly from that used in adult practice, in that great reliance was placed on the loss of resistance felt as the needle point passed through the thigh muscles into the sciatic neurovascular compartment. There were no immediate or late complications associated with this block in any of the patients. It is concluded that the block is easy to perform and can produce reliable postoperative analgesia for most common operations on the foot and ankle in paediatric practice. PMID- 4014615 TI - Nitrous oxide solubility in halothane and its effect on the output of vaporizers. AB - The absorption of nitrous oxide in halothane was studied by bubbling nitrous oxide and nitrous oxide/oxygen gas mixtures through a halothane bottle, using 100% oxygen as a control. The gas volume emerging from the halothane bottle was measured each minute, over a period of up to 15 minutes. When oxygen was used as a control gas, the averaged flow rate dropped slightly over the experimental period, due to the cooling of the halothane. However, in the presence of nitrous oxide, the initial flow rate of the gas emerging from the halothane bottle was greatly diminished, but then accelerated rapidly to reach that obtained with oxygen. The results suggested that nitrous oxide dissolved in large quantities in halothane, and the data are consistent with an Ostwald coefficient in excess of 4.0. PMID- 4014616 TI - Some predisposing factors to hypersensitivity reactions following first exposure to Althesin. AB - Three possible factors predisposing to Althesin hypersensitivity, namely total dose, method of administration, either by bolus dose or infusion, and pregnancy have been studied in patients receiving the drug for the first time. Of 137 patients given Althesin, four exhibited clinical signs of mild hypersensitivity, while C3 conversion alone, indicative of a subclinical reaction, was seen in a further six patients. No reactions were observed in two control groups in whom anaesthesia was induced with thiopentone. Neither the total dose nor method of administration appeared consistently to influence the incidence of reactions, but eight of the ten patients producing an altered response to Althesin were pregnant. PMID- 4014617 TI - Self-administered isoflurane in labour. A comparative study with Entonox. AB - Entonox (50% nitrous oxide in oxygen) and isoflurane (0.75% in oxygen) were compared as analgesics in the first stage of labour in 32 consenting women. The drugs were self-administered and given in random sequence, each during five consecutive uterine contractions. Each patient acted as her own control. Linear analogue pain scores were significantly lower (p less than 0.001) with isoflurane than with Entonox, but scores for drowsiness were higher for isoflurane. Further study is needed to assess the effects of more prolonged use of isoflurane in labour. PMID- 4014618 TI - Plasma bupivacaine levels associated with extradural anaesthesia for caesarean section. AB - Plasma bupivacaine levels were measured in 47 women undergoing extradural Caesarean delivery. They were divided into four groups according to the following dose regimens using 0.5% bupivacaine. Group A were given a bolus of 20 ml with increment after 20 minutes. Groups B and C were given 10 ml initially with further increments if required at 10 minutes (group B) and 20 minutes (group C); Group D consisted of patients who had an extradural block extended for emergency Caesarean delivery. In the elective groups the highest and most rapidly achieved values were associated with group A and the lowest levels found in group C. The highest levels of all were found in the emergency group. The investigation indicates that slow controlled induction of extradural anaesthesia for Caesarean section greatly reduces the risk of local anaesthetic toxicity. PMID- 4014619 TI - Cardiovascular and cerebral complications during glossopharyngeal nerve thermocoagulation. AB - The cardiovascular and cerebral complications observed during percutaneous radiofrequency thermocoagulation of the glossopharyngeal nerve are described. The value of such symptoms in anticipating a lesion of the vagus nerve is discussed. PMID- 4014620 TI - Effect of premedication with controlled-release oral morphine on postoperative pain. A comparison with intramuscular morphine. AB - Thirty fit patients presenting for elective total hip replacement were randomly allocated to receive a premedication of 60 or 90 mg controlled-release oral morphine or 15 mg intramuscular morphine. Postoperative analgesia was assessed using on-demand intravenous pethidine supplementation requirements. In 15 patients free plasma morphine concentrations were measured. Both 60 and 90 mg controlled-release oral morphine led to a reduced pethidine requirement compared to the intramuscular group but the reduction was not statistically different. PMID- 4014621 TI - Tracheal tube cuff pressures. The effects of different gas mixtures. AB - Changes in cuff pressure and volume of tracheal tubes were studied in 60 patients undergoing lower abdominal surgery under general anaesthesia with nitrous oxide and oxygen as the anaesthetic gas mixture. The cuffs were inflated with either anaesthetic gas mixture or air. Three different brands of tubes were used. The pressure in the air filled cuffs increased steadily throughout the procedure and reached level high enough to impede microcirculation in the tracheal mucosa within one hour. We conclude that filling the cuff with anaesthetic gas mixture is a simple and reliable way to achieve stable cuff pressure during anaesthesia. PMID- 4014622 TI - Anaesthetic experience with percutaneous lithotripsy. A review of potential and actual complications. AB - Percutaneous lithotripsy has evolved over the last several years as a procedure for removing renal calculi via percutaneous puncture of the renal collecting system. This article reviews our initial anaesthetic experience with 48 procedures and identifies both actual and potential complications. The most significant complication identified is instillation of large volumes of irrigation fluid into the retroperitoneal space. Two cases of metabolic acidosis and abdominal distension are presented. One responded to treatment while the other progressed to a fatal disseminated intravascular coagulopathy. Recommendations to prevent this are given. PMID- 4014623 TI - Isolated intrapulmonary haemorrhage. An unusual complication of internal jugular vein cannulation. AB - A case of intrapulmonary haemorrhage following internal jugular vein cannulation is described and the subsequent treatment outlined. A cautionary note is expressed, especially when the procedure is performed in obese, thick-set individuals with chronic lung disease. PMID- 4014624 TI - Automatic blood pressure monitors. A clinical evaluation of five models in adults. AB - Five automatic blood pressure monitors were evaluated by comparing their values with almost simultaneous blood pressure readings from radial artery catheters. A total of 583 comparisons were made on 48 patients. Statistical analysis was performed on the pooled comparisons of systolic and diastolic pressure for each monitor. Agreement between the pressure measurements was variable between both patients and machines. For systolic pressure, two machines (Copal and Sentron) had correlation coefficients of over 0.9 while for the other machines (Dinamap 845XT, Narco and Vitastat 9001S) the values lay between 0.7 and 0.8. The steepest regression lines were also found with the Copal (0.93) and Sentron (0.86) data, but the other machines had considerably flatter slopes (0.55 to 0.67). The intercepts on the Y axes ranged from +14.1 (Copa) to +50.1 (Dinamap). In clinical use, popularity of the different machines reflected the degree to which the machine reproduced the behaviour of the direct pressure measurement. PMID- 4014625 TI - Hard questions in intensive care. A moralist answers questions put to him at a meeting of the Intensive Care Society, Autumn, 1984. PMID- 4014626 TI - Systemic absorption of lignocaine ointment from tracheal tubes. AB - Arterial plasma concentrations of lignocaine were studied in fifteen adult patients following insertion of a tracheal tube whose cuff area was smeared with 5% lignocaine ointment. Twelve patients had 2 ml of ointment (114 mg) and samples were taken every 5 minutes until 30 minutes and in eight of the 12 patients at 40, 50 and 60 minutes after insertion and inflation of the tracheal tube and cuff. Three patients had 1 ml of ointment on the tube and were studied over 60 minutes. Plasma concentrations were determined using gas liquid chromatography. In the 2 ml lignocaine group mean plasma lignocaine levels were 1.9 (SD 0.9) micrograms/ml at 10 minutes, 2.3 (SD 0.8) micrograms/ml at 20 minutes, 2.3 (SD 0.8) micrograms/ml at 30 minutes and 1.7 (SD 1.0) micrograms/ml at 60 minutes. After 1 ml of lignocaine, levels were 1.2 (SD 0.1) micrograms/ml at 10 minutes, 1.1 (SD 0.7) micrograms/ml at 20 minutes, 0.8 (SD 0.3) micrograms/ml at 30 minutes and 0.75 (SD 0.1) micrograms/ml at 60 minutes. PMID- 4014627 TI - A resuscitation box for every anaesthetist? AB - The results are reported of a questionnaire which asks whether or not anaesthetists routinely carry any resuscitation equipment in their cars. A small, simple resuscitation box is described which is adequate for the majority of life threatening situations. PMID- 4014628 TI - Failure of magnesium sulphate to prevent suxamethonium induced muscle pains. AB - In fit unpremedicated patients undergoing minor operations and who were ambulant on the afternoon of the operations, pretreatment with magnesium sulphate given intravenously did not reduce the incidence of suxamethonium induced myalgia below that in a similar series who received no prophylactic therapy. The injection of magnesium in conscious patients is followed by unpleasant side effects. PMID- 4014629 TI - Meptazinol as an analgesic adjunct to total intravenous anaesthesia in cystoscopy patients. AB - Sixty-four unpremedicated patients undergoing cystoscopy received either intravenous meptazinol 2 mg/kg or saline in equivalent volume in a randomised, double-blind manner immediately before induction of anaesthesia with Althesin. Inclusion of meptazinol reduced the total dose of anaesthetic required, allowed a more rapid recovery and was associated with less movement in response to surgery. The patients in the control group tended to hyperventilate, and had lower end tidal CO2 tension (p less than 0.001), and also higher pulse rates during surgery (p less than 0.01) than the meptazinol group. However, the patients who received meptazinol had a more frequent incidence of complications during induction and recovery (p less than 0.05). PMID- 4014630 TI - Entonox hazard. PMID- 4014631 TI - Peri-operative plasma glucose in children. PMID- 4014632 TI - Ergometrine and death from acid aspiration. PMID- 4014633 TI - Epidural analgesia: a valuable precaution. PMID- 4014634 TI - Delayed cardiorespiratory depression following nalbuphine administration. PMID- 4014635 TI - The glass bead game. PMID- 4014636 TI - A comparison of different concentrations of lignocaine hydrochloride used for topical anaesthesia of the larynx of the cat. AB - Electromyographic (EMG) recordings were made from the intrinsic laryngeal muscles (cricothyroid, thyroarytenoid) and the diaphragm of the cat to compare the effect of the same dose of different concentrations of lignocaine hydrocholoride applied topically to the laryngeal mucosa. All concentrations of lignocaine hydrochloride tested, two, five and ten per cent, produced desensitisation of the larynx, as demonstrated by a loss of response of the crocothyroid and thyroarytenoid to mechanical stimulation of the mucosa. Desensitisation was produced in a mean of 1.80 minutes in the thirty experiments performed. Return of baseline response took significantly longer when 5 or 10% lignocaine was used compared with that when 2% was used (p less than 0.05). The usefulness of lignocaine hydrochloride as a topical anaesthetic for the larynx is reviewed. PMID- 4014637 TI - Pacemaker reversion for suspected supraventricular tachycardia. AB - Overdrive atrial pacing was employed in twelve patients with suspected supraventricular tachycardia resistant to drug therapy. Eleven of these patients reverted to sinus rhythm with pacing either immediately or after a short episode of atrial fibrillation. In one patient, recordings from the atrial electrode indicated that a broad complex tachycardia was of ventricular rather than supraventricular origin. No complications were encountered and the procedure was well tolerated in all. Overdrive pacing is suggested as a safe alternative to DC cardioversion in drug-resistant supraventricular tachycardia, particularly in the presence of digitalis, in the elderly and in patients with chronic lung disease. PMID- 4014638 TI - Implications for vigilance of a method for evaluating patterns of change in heart rate during anaesthesia. AB - Instantaneous heart rate was recorded in five patients and analysed for change in rate using the criterion of percentage variation either side of the starting rate with resetting throughout the anaesthetic each time the permitted variation was exceeded. The number of occasions on which change occurred was counted, the patterns of change were analysed and the effect of two sampling methods (six second sample and six-second average) on these patterns was compared. A large number of patients (131) was investigated using the six-second sampling method and the number of changes and patterns of change were evaluated. It is suggested that the six-second sampling technique, combined with the 10 or 15% variation, may be useful for the evaluation of vigilance, and has implications for the design of monitoring apparatus in the future. PMID- 4014639 TI - A comparison of continuous flush devices. AB - Six different makes of continuous flush device were compared for reliability of flow rate and ease of use. All of the devices tested were considered suitable for flushing of vascular pressure monitoring catheters. However, flow rates were considered too variable for control of drug infusions or flushing of intracranial pressure monitoring systems. PMID- 4014640 TI - An overhead heater for use in infant anaesthesia. PMID- 4014641 TI - Interpretation and critical appraisal of journal articles. PMID- 4014643 TI - Spinal anaesthesia in obstetrics. PMID- 4014642 TI - Rhabdomyolytic renal failure and suxamethonium. PMID- 4014644 TI - Atropine and caesarean section. PMID- 4014645 TI - Management of chest injuries. PMID- 4014646 TI - The management of acute haemorrhage. PMID- 4014647 TI - Accidental dural puncture. PMID- 4014648 TI - Amitriptyline and ephedrine in subarachnoid anaesthesia. PMID- 4014649 TI - Mouth to mask ventilation. PMID- 4014651 TI - Scavenging misconnection. PMID- 4014650 TI - Multiple uses for a new 'T' piece. PMID- 4014652 TI - Oxygen supply at risk. PMID- 4014653 TI - Analysis of the calcium-dependent interaction of calmodulin with bovine serum albumin. AB - An air-driven ultracentrifuge has been used to investigate the calcium-dependent association between calmodulin and bovine serum albumin. Procedures were described which allowed the interaction to be analyzed to yield the equilibrium constant. At low ionic strength (25 mM Tris-HCl, pH 7.5, pCa 6.68, 9 degrees C) the equilibrium constant for the interaction was estimated to be 2.1 X 10(4) M-1, while at high ionic strength (25 mM Tris-HCl, pH 7.5, 150 mM KCl, pCa 6.68, 9 degrees C) the value was 4.5 X 10(3) M-1. Under similar conditions, calmodulin was also found to interact with beta-lactoglobulin A and gelatin, but no detectable association was observed with ovalbumin. PMID- 4014654 TI - Anaerobic multiphasic gel electrophoresis of the molybdoproteins in extracts of Clostridium pasteurianum. AB - Simple procedures using multiphasic buffer systems for anaerobic electrophoresis have been devised to identify oxygen-labile metalloproteins. An anaerobic slab gel apparatus was developed with cooling and design for anaerobic conditions. Included is a procedure to remove sample wells after stacking proteins in a crude extract, to prevent streaking (background) caused by continuous leakage of "nonstacked protein" from the sample wells. Identification of eleven Mo zones in extracts of Clostridium pasteurianum demonstrates the usefulness of the technique in identifying radiolabeled oxygen-labile proteins in cell-free crude lysates. PMID- 4014655 TI - Determination of inorganic phosphate with molybdate and Triton X-100 without reduction. AB - A new colorimetric procedure is described for inorganic phosphate determination using the color reaction between inorganic phosphate and acidified ammonium molybdate in the presence of Triton X-100. The method is simple and specific, and produces results comparable with those of the widely used method of Fiske Subbarow [C. H. Fiske and Y. Subbarow (1925) J. Biol. Chem. 66, 375]. The linearity of the standard curve is observed up to an absorbance of 0.410, compared to 0.370 in the Fiske-Subbarow method. Trichloroacetic acid and tungstic acid are found to interfere in the assay. However, the method is not disturbed by nonionic detergents and can therefore be used for the determination of inorganic phosphate contaminated with nonionic detergents. PMID- 4014656 TI - Small sucrose density gradients: reproducible and automatic fractionation using a commercial fraction collector (Pharmacia). AB - A simple, inexpensive modification of a programmable commercial fraction collector (Frac 100; Pharmacia, Sweden) was described. This modification allowed reproducible automatic fractionation of small sucrose gradients by rinsing the hanging drop at the delivery head of the fraction collector into the sampling tube, using signals from the fraction collector to control this specialized function. The described principle may also be useful whenever fraction size is near to drop volume and high resolution and reproducibility are desired. PMID- 4014657 TI - High-performance liquid chromatographic analysis of metabolites of the nicotine derived nitrosamines, N'-nitrosonornicotine and 4-(methylnitrosamino)-1-(3 pyridyl)-1-butanone. AB - An improved high-performance liquid chromatographic system was developed for separation of 11 metabolites of the nicotine-derived nitrosamines N' nitrosonornicotine (NNN) and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). The new system employed a 5-microns octadecylsilane bonded column eluted with aqueous sodium acetate-methanol gradients of varying pH. Analysis times were typically 30 min for NNN metabolites and 50 min for NNK metabolites, compared to 80 and 90 min, respectively, when 10-microns columns were used. The E and Z isomers of all nitrosamine-containing metabolites of NNK were separated. The chromatographic behavior of the 11 metabolites as well as NNN and NNK was studied between pH 4.0 and 7.5. The retention times of several metabolites were altered significantly as a function of pH. The results of the pH study provide valuable additional criteria for metabolite identification as well as optimized conditions for their separation. Applications of the system to the metabolism of [2'-14C]NNN in cultured rat esophagus and [carbonyl-14C]NNK in rat liver slices are presented. PMID- 4014658 TI - Microquantitative analysis of neutral and amino sugars as fluorescent pyridylamino derivatives by high-performance liquid chromatography. AB - A method for the quantitation of picomole amounts of neutral and amino sugars in glycoconjugates was developed. Glycoconjugates were hydrolyzed with a mixture of equal amounts of 4 M trifluoroacetic acid and 4 M hydrochloric acid, and the free amino groups were acetylated. Sugars were coupled with 2-aminopyridine. After the excess reagents were removed by gel-permeation high-performance liquid chromatography, the fluorescent pyridylamino derivatives of sugars were separated and quantified by high-performance liquid chromatography on a reversed-phase column. This method allowed the determination of 0.01-10 nmol of sugars. About 100 pmol of several glycoconjugates were analyzed by the present method, with satisfactory results. PMID- 4014659 TI - Gas chromatography-mass spectroscopy analysis of juvenile hormone released by insect corpora allata. AB - Corpora allata incubated in appropriate medium release several compounds including juvenile hormones. Juvenile hormones (14C labeled or unlabeled) were extracted with hexane and directly analyzed by gas chromatography-mass spectroscopy. This method allowed the qualitative and quantitative analysis of total released juvenile hormone. It could also be used as a routine assay for evaluation of corpus allatum activity. Data obtained by this method were compared to those obtained by radiochemical assay. PMID- 4014660 TI - A method for quantitative analysis of ratios of types I and II collagen in small samples of articular cartilage. AB - Currently available methods for quantitative analysis of type II collagen in studies of articular cartilage repair either require much larger samples than are available or are inaccurate and unreliable. A method of determining the percentage of type II collagen in small samples of articular cartilage (100 to 200 micrograms) by measuring the spectrophotometric densities of specific cyanogen bromide peptide bands from mixtures of types I and II collagen on sodium dodecyl sulfate-polyacrylamide gels has been developed and found to be accurate and very reliable. The ratio of the area under the alpha 1(II)CB10 peak to the area under the alpha 1(I)CB7,8 + alpha 1(II)CB11 peak was function of the proportion of type II collagen in the sample. Since the ratio was independent of the quantity of sample loaded onto the gel, it was not affected by moderate losses of sample. This method should therefore be useful in the fields of collagen research and particularly valuable to those investigating the repair and regeneration of articular cartilage. PMID- 4014661 TI - Oxygen consumption of mammalian myocardial cells in culture: measurements in beating cells attached to the substrate of the culture dish. AB - A Lucite attachment which permitted the measurement of oxygen consumption in cells in culture without manipulating the cells was constructed. The attachment fit over commercially available dishes for cell culture and had an oxygen electrode built into it. Oxygen uptake of cells in culture was thus measured. Cells were attached to the substrate of the culture dish during the measurements and could be observed in an inverted phase microscope. Cells did not show any morphological changes, e.g., cell shapes or beating rate in case of myocardial cells, before and after the measurements of oxygen consumption. Using this method the rate of oxygen consumption was determined in rat myocardial and heart non muscle cells in culture and also in HeLa and L6 cell lines. Myocardial cells in culture had an approximately four times higher rate of oxygen uptake compared with heart non-muscle, HeLa, and L6 cells. The oxygen uptake of beating myocardial cells was higher by about 50% compared with quiescent myocardial cells. PMID- 4014662 TI - Coupling of peptides to protein carriers by mixed anhydride procedure. AB - Carboxyl groups of succinylated bovine serum albumin were activated by isobutylchloroformate in dimethylformamide solution. Subsequent reaction of the mixed anhydride with amino groups of the added peptide provided rapid and efficient coupling of peptide to protein. For different peptides the yield of coupling was equal to 40-100%. These values corresponded to 20-50 mol peptide bound/mol protein. Immunization of rabbits with these conjugates produced antisera to peptides with titers of 1:1000-1:3000 (estimated by enzyme-linked immunosorbent assay). PMID- 4014663 TI - High-pressure liquid chromatography of neutral oligosaccharides: effects of structural parameters. AB - Sixty-five neutral oligosaccharides were analyzed by high-pressure liquid chromatography on an amine-modified silica column (Lichrosorb-NH2). By systematic comparison of the retention times, it was possible to attribute chromatographic behavior to specific structural features. It appeared that retention times increase with the number of sugar residues. The presence of a fucose or an N acetylglucosamine residue results in a decreased retention time, in particular when the latter sugar is at the reducing end. A dramatic increase in retention time is shown by oligosaccharides having a 1----6 linkage, regardless of whether this linkage is involved in a branch. Less important features are the nature of the component sugars other than N-acetylglucosamine and fucose, the anomeric configuration of the sugars, and the presence of a reduced terminal sugar. PMID- 4014664 TI - Treatment of dialysis membranes for simultaneous dialysis and concentration. AB - Dialysis membranes used for simultaneous dialysis-concentration required pretreatment to remove uv-absorbing compounds leached from the membranes and to reduce the absorption of protein to the membranes. This was accomplished with sodium carbonate and ethanol or with "sulfur-removal solutions." Protein determinations were made with a micro-Bradford protein reaction and with uv absorbance at 280 nm. Soluble membrane components contributed to aberrant uv spectra and altered the ratio of 280/260-nm absorbance. Simultaneous dialysis and concentration in the micro protein dialyzer-concentrator apparatus, combining aspects of thin-layer dialysis and ultrafiltration, resulted in rapid removal of salts from the protein solutions. Prior treatment of membranes reduced uncertainties in retentate recoveries, eliminated uv-absorbing components of membranes, and improved recoveries of protein. PMID- 4014665 TI - Isolation of enzymes from polyacrylamide disk gels by a centrifugal homogenization method. AB - A sliced segment of polyacrylamide gel was quickly homogenized without any loss of gel pieces. The gel segment was placed on a disposable pipet tip, which was packed with a small amount of lumped copper wires and held in a microfuge tube. The gel was homogenized by centrifugation for 15 s at 15,000 g at 0 to 4 degrees C. Almost 70% of endodextranase activity could be recovered from homogenized gel within 30 min at 4 degrees C, whereas only 20% of activity was eluted from gel slices. If necessary, copper wire could be replaced by fine stainless-steel wire or by the nylon string used in fishing lines. Proteins could also be recovered from the homogenized gel by charging electric current for 1 h at 4 degrees C. PMID- 4014666 TI - Gas chromatographic-mass spectrometric determination of isotopic enrichment of 6 15NH2 in adenine nucleotides. AB - A gas chromatographic-mass spectrometric method for the determination of isotopic abundance in [6-15NH2]adenine nucleotides is described. The method involves formation of the di-t-butyldimethylsilyl (TBDMS) derivative of adenine following isolation of the nucleotide fraction with solid-phase ion-exchange chromatography and subsequent acid hydrolysis of nucleotides to free base. Mass spectra for both adenine-diTBDMS and [6-15NH2]adenine-diTBDMS were obtained to identify those ions containing the 6-NH2 moiety. The base peak (m/z 306) was formed by loss of C4H9 (57) and constitutes approximately one-third of the total ion current. Using selected ion monitoring of the m/z 306/m/z 307 ratio, levels of isotopic abundance of 1.0-50.0 mol% excess could be measured reproducibly with the injection of 10-20 pmol of the adenine-diTBDMS derivative obtained from isolated rat hepatocytes. Confirmation that measured isotopic abundance was referable to labeling of the 6-15NH2 group was obtained by oxidation of adenine to hypoxanthine and determination of enrichment in the hypoxanthine-diTBDMS derivative. The method was used to study the formation of [6-15NH2]adenine nucleotides during the incubation of isolated rat hepatocytes with [15N]alanine. A level of approximately 6.0 mol% excess was observed at 60 min incubation. PMID- 4014667 TI - A spectrophotometric resin competition procedure to determine dissociation constants for metal ion-nucleotide complexes. AB - The resin competition method for determining the dissociation constants of metal ion-nucleotide complexes was modified to take into account the fact that some metal nucleotide complexes are anionic and thus, like the free nucleotide, will bind to the resin. A simple, rapid spectrophotometric titration procedure is given for the determination of both the metal ion-nucleotide complex dissociation constant and the ratio of the affinities of the nucleotide and its complex for the resin. PMID- 4014668 TI - New spectrophotometric and radiochemical assays for acetyl-CoA: arylamine N acetyltransferase applicable to a variety of arylamines. AB - Simple and sensitive spectrophotometric and radiochemical procedures are described for the assay of acetyl-CoA:arylamine N-acetyltransferase (NAT; EC 2.3.1.5), which catalyzes the reaction acetyl-CoA + arylamine----N-acetylated arylamine + CoASH. The methods are applicable to crude tissue homogenates and blood lysates. The spectrophotometric assay is characterized by two features: (i) NAT activity is measured by quantifying the disappearance of the arylamine substrate as reflected by decreasing Schiff's base formation with dimethylaminobenzaldehyde. (ii) During the enzymatic reaction, the inhibitory product CoASH is recycled by the system acetyl phosphate/phosphotransacetylase to the substrate acetyl-CoA. The radiochemical procedure depends on enzymatic synthesis of [3H]acetyl-CoA in the assay using [3H]acetate, ATP, CoASH, and acetyl-CoA synthetase. NAT activity is measured by quantifying N [3H]acetylarylamine after separation from [3H]acetate by extraction. Product inhibition by CoASH is prevented in this system by the use of acetyl-CoA synthetase. PMID- 4014669 TI - Dynamic headspace analysis of volatile metabolites from the reductive dehalogenation of trichloro- and tetrachloroethanes by hepatic microsomes. AB - A dynamic headspace technique was developed to facilitate the identification and quantitation of low levels of volatile metabolites produced in vitro by subcellular preparations. The method is complementary to commonly used static headspace and solvent-extraction techniques, and involves purging the compounds from microsomal suspensions with an inert gas, trapping them on a short column of adsorbant resin, and transferring the metabolites to a gas chromatograph. An apparatus was designed to facilitate the incubations and isolations of volatile compounds. Recoveries of several chlorinated hydrocarbons with boiling points in the range 12 to 186 degrees C were 85% or higher, and the recovery of vinyl chloride (boiling point -13 degrees C) was 25%. The quantitative precision of the method was determined and calibration curves were established for each metabolite, demonstrating that no discrimination occurred over a wide range of concentrations. This technique was employed to investigate the reductive metabolism of 1,1,1-trichloroethane, 1,1,2-trichloroethane, and 1,1,2,2 tetrachloroethane by rat liver microsomes. The metabolites from these substrates were 1,1-dichloroethane, vinyl chloride, and 1,2-dichloroethylene, respectively. These conversions were NADPH-dependent, occurred only under anaerobic conditions, and indicate that chloroethanes with relatively low electron affinities can be reduced slowly by microsomal cytochrome P-450. The rates of formation of vinyl chloride, 1,1-dichloroethane, and 1,2-dichloroethylene with 1.0 mM substrate were 12.5 +/- 2.0, 122 +/- 14, and 147 +/- 12 pmol/min/mg of protein, respectively. The results show that there are distinct advantages of the purge/trap method over the static headspace method for studying volatile metabolites when high sensitivity is required. PMID- 4014670 TI - Synthesis, storage, and stability of [4-14C]oxaloacetic acid. AB - A simple procedure for preparing [4-14C]oxaloacetic acid based on the reaction between [14C]HCO-3 and phosphoenolpyruvate catalyzed by phosphoenolpyruvate carboxylase is described. A simple method for preparing highly purified phosphoenolpyruvate carboxylase from maize leaves is described and the degradation of oxaloacetate under conditions of varying pH and divalent metal ion concentration is reported on. [4-14C]Oxaloacetic acid is stable for several months in 0.1 M HCl solution at -80 degrees C. PMID- 4014671 TI - New spectrophotometric assays of acid lipase and their use in the diagnosis of Wolman and cholesteryl ester storage diseases. AB - Trinitrophenylaminolauric acid (TNPAL) was linked to glycerol or cholesterol and the resulting yellow compounds were used as substrates for several lipases and cholesteryl esterase in cells from normal individuals and patients with Wolman's or cholesteryl ester storage diseases. Normal cells (lymphoid cell lines or skin fibroblasts) showed two peaks of lipase or cholesteryl esterase activity at about pH 4.0 and 6.0 each. The activity of the most acidic enzyme, which hydrolyzed natural or synthetic triacylglycerols as well as cholesteryl esters, was considerably reduced in cells derived from patients with Wolman's or cholesteryl ester storage diseases. Simple spectrophotometric procedures were developed for using tri-TNPAL glycerol or TNPAL cholesterol to identify homozygotes of these two respective diseases. PMID- 4014672 TI - O2 solubility in aqueous media determined by a kinetic method. AB - A kinetic method for the determination of O2 solubility in air-saturated aqueous solutions of widely varying composition and temperature is described. It is based on the precise molar stoichiometry between the rates of uptake of H+ and O2, measured with response-matched electrodes, in the reaction NADH + H+ + 1/2O2--- NAD+ + H2O, catalyzed by an NADH oxidase preparation. To the initially anaerobic test system, which contains an excess of NADH and NADH oxidase in a buffered medium, an aliquot of the O2-containing solution to be tested is added and the rates of both O2 uptake and H+ uptake are recorded; the H+ electrode is calibrated against standard HCl. From these data the amount of O2 in the aliquot is calculated. Some representative values for O2 solubility at 25 degrees C and 760 mm in air-saturated systems are (i) distilled H2O, 516 nmol O/ml, (ii) 0.15 M KCl, 480 nmol O/ml, and (iii) 0.25 M sucrose, 458 nmol O/ml. Data and equations are also given for the solubility of O2 at 760 mm in air-saturated and lightly buffered 0.15 M KCl and 0.25 M sucrose over the range 5 to 40 degrees C. In the method described the rates of O2 and H+ uptake are precisely linear and stoichiometric when NADH is present in large excess over O2. However, when O2 is in excess and small additions of 340-nm-standardized NADH are made, as in earlier methods based on NADH oxidation, the endpoint is approached very gradually and tends to overestimate O2 solubility, owing to (i) the higher Km for NADH than for O2, (ii) the relatively slow response of the Clark O2 electrode, and (iii) the incomplete oxidation of NADH in the presence of 340-nm-absorbing inhibitory substances. PMID- 4014673 TI - Estimation of liposome integrity by 1H-NMR spectroscopy. AB - A fast and simple method of 1H-NMR spectroscopic control of liposome membrane integrity is suggested. The method is based on the redistribution of intensities between two singlet 1H-NMR signals--from intraliposomal marker compound (nitrilotriacetic acid sodium salt, 1H-NMR signal at 4 p.p.m.) and from its complex with Eu3+ added to the external medium (NMR signal of the complex at - 1 p.p.m.). The method permits registration of the kinetics of liposome destruction under the action of detergent or serum. It is shown that the presence of cholesterol in the membrane makes it more stable. PMID- 4014674 TI - Proteins transferred to nitrocellulose for use as immunogens. AB - Proteins were separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and were eluted efficiently from the gel by transfer to nitrocellulose paper. The protein-bearing nitrocellulose was solubilized with dimethyl sulfoxide and used as an immunogen in rabbits. Polyclonal antibodies to the proteins were generated. PMID- 4014675 TI - Purification of beta-glucocerebrosidase by preparative-scale high-performance liquid chromatography: the use of ethylene glycol-containing buffers for chromatography of hydrophobic glycoprotein enzymes. AB - beta-Glucocerebrosidase, partially purified by the method of F. S. Furbish et al. (1977, Proc. Natl. Acad. Sci. USA 74, 3560-3563), was shown by sodium dodecyl sulfate-polyacrylamide gel electrophoresis to contain, in addition to the desired enzyme, variable amounts of a very hydrophobic contaminant (apparent Mr 45,000). Purification of the enzyme was accomplished by gel-permeation HPLC on a TSK 3000 SW column (0.7 X 60 cm). Adsorptive losses of protein on the column were minimized by using buffers containing up to 50% ethylene glycol. We have examined the effects of varying the ethylene glycol concentration on the elution times and recoveries of the two major proteins in this preparation. The high reproducibility of the individual chromatograms permitted the use of an automatic sampler and fraction collector to perform multiple, continuous runs for the purification of milligram quantities of enzyme. Multiple runs of a preparative scale column, TSK G3000 SWG (2.15 X 60 cm), permitted gram-scale purification of beta-glucocerebrosidase without loss in efficiency of separation. Recovery of enzyme activity is greater than 94% with less than 1% contamination by other proteins. Reaction of enzyme prepared in this fashion with rabbit polyclonal antiserum or mouse monoclonal anti-beta-glucocerebrosidase shows the enzyme to be pure and not immunologically related to the 45,000 Mr contaminant. The specific activity of enzyme prepared by this means is 1.6 X 10(6) nmol/h/mg protein. Inclusion of ethylene glycol in buffers was shown to overcome hydrophobic protein interactions with TSK 3000 SW column matrices for both the soluble human lysosomal enzyme alpha-galactosidase A and the plant toxin ricin. PMID- 4014676 TI - Solid-phase radiolabeling of glycolipids with galactose oxidase and sodium boro[3H]hydride. AB - Neutral glycosphingolipids immobilized on plastic surfaces were specifically radiolabeled with the galactose oxidase-sodium boro[3H]hydride method. Glycolipids could be immobilized in the absence of any other lipids such as phosphatidylcholine and cholesterol. Rather, the presence of these lipid components decreased the efficiency of radiolabeling. Glycolipids having more than four carbohydrate moieties with terminal galactosyl residues were effectively radiolabeled and could be easily recovered by elution from the plastic with ethanol in one step. This method will be suitable for analysis of small samples of "upper-phase" neutral glycolipids having terminal galactose or N acetylgalactosamine. PMID- 4014677 TI - Microsequence analysis of peptides and proteins. V. Design and performance of a novel gas-liquid-solid phase instrument. AB - We describe the construction and performance of a novel, automated, Edman chemistry-based microsequencer. The reagent and solvent delivery system, the reaction cartridge for coupling and cleavage, and the conversion flask are all constructed from chemically inert perfluoroelastomers. The delivery valves are of a new design incorporating the use of electromagnetically actuated solenoids and zero-dead-volume construction, and may be connected in a modular fashion resulting in multiple inputs with a single output line which can be flushed with inert gas. The bottle closures are of a new design based on an all-Teflon compression fitting. The reaction cartridge and conversion flask are thermostated by solid-state heaters in an aluminum block. The overall size of the instrument is 25 X 34 X 14 in. The chemistry utilizes 2% aqueous triethylamine as the coupling base which is delivered to the reaction cartridge via a stream of nitrogen. The "gas-phase" delivery of the coupling base and the cleavage acid (trifluoroacetic acid) is modeled after the method described by R. M. Hewick et al. (J. Biol. Chem. 256, 7990-7997,1981). The instrument has performed well over a period of 3 years in terms of low background peaks, sensitivity in the picomole range, and reliability of operation. The use of economical components, ease of construction and operation, and sensitive analytical capability make this instrument a useful tool for microsequence analysis of peptides and proteins. PMID- 4014678 TI - An amino-terminal tryptophan derivative which is refractory to Edman degradation. AB - A new derivative of tryptophan is proposed to account for the observation that some peptides having amino-terminal tryptophan residues become refractory to Edman degradation. An acid-catalyzed oxidation of the indole nucleus and subsequent cyclization to a unique 3-anilinopyrrolidin-2-one derivative with cleavage of the peptide chain is the most likely chemical explanation. This amino acid is reactive with ninhydrin and contains an aryl amine. However, the amine does not bond to the alpha carbon so while reactive to phenyl isothiocyanate, distances are too great for the residue to be cleaved from the peptide during Edman degradation. PMID- 4014679 TI - Product analysis of in vitro ribosomal protein synthesis for the assessment of kinetic parameters. AB - For the characterization of the product distribution of in vitro ribosomal protein synthesis a new method is introduced in which radioactively labeled peptides are separated on a reversed-phase HPLC column and detected on line with a flow radioactivity monitor. Employing this procedure the kinetics of product formation under pre-steady-state conditions were measured under a variety of conditions. These measurements yield the intrinsic monomolecular rate constants for peptidyl transfer (greater than 20 s-1) and translocation (rate limiting for elongation). The usefulness of this technique for accuracy measurements is illustrated. PMID- 4014680 TI - Labeling of cysteine-containing peptides with 2-nitro-5-thiobenzoic acid. AB - A method for specific labeling of cysteine-containing peptides has been developed using Ellman's reagent, 5,5'-dithiobis(2-nitrobenzoic acid) (DTNB). Prior to cleavage with proteases or chemical reagents, proteins are reacted with DTNB, resulting in the formation of a mixed disulfide between the protein sulfhydryl group and 2-nitro-5-thiobenzoic acid (TNB). The formation of the mixed disulfide introduces a chromophore, with an absorbance peak at 328 nm. By monitoring peptide maps generated by HPLC at 210 and 328 nm, peptides containing cysteine residues are readily identified. The stability of the derivative was tested using glutathione-TNB as a model compound. Glutathione-TNB is stable to conditions used for CNBr cleavage, as well as those for tryptic cleavage. The TNB label may also increase the hydrophobicity of small peptides, which otherwise might not bind to reverse-phase matrices. This was the case for an oxidatively modified tetrapeptide isolated from Escherichia coli glutamine synthetase. PMID- 4014682 TI - Relative molecular weight and concentration determination of sodium hyaluronate solutions by gel-exclusion high-performance liquid chromatography. AB - Gel-exclusion chromatography coupled with HPLC instrumentation can be used to determine the molecular weight of highly purified sodium hyaluronate in solution. The method is very reproducible, precise, and rapid, and allows molecular weight determinations up to 2 million to be done in the presence of considerable impurities. This technique offers considerable advantages over traditional light scattering, sedimentation equilibrium, and viscometry methods for molecular weight determinations, in that HPLC-gel exclusion is rapid and not subject to errors arising from impurities. Simultaneous with molecular weight measurements, sodium hyaluronate concentrations can be determined with a lower range of 0.1 to 0.3 mg/ml dependent upon the sensitivity of the refractive index-detecting system. Unlike the carbazole reaction, this technique is unaffected by low molecular-weight impurities such as monosaccharides or substances with relative molecular weights less than 18,000. PMID- 4014681 TI - Immunodetection with streptavidin-acid phosphatase complex on Western blots. AB - A technique for the detection of nanogram amounts of protein blotted onto nitrocellulose membranes has been developed using nonradioactive probes. Protein transferred to nitrocellulose membranes is detected by a specific antibody followed by incubation with biotinylated anti-antibody. After addition of streptavidin-acid phosphatase complex, incubation with fast violet B salt produces sharp magenta bands. This method allows detection of bands containing less than 20 ng of protein. The procedure does not use radioactive or carcinogenic materials. PMID- 4014683 TI - Immunodetection of nitrocellulose-adhesive proteins at the nanogram level after trinitrophenyl modification. AB - A method for protein detection on nitrocellulose membranes based on modification with 2,4,6-trinitrobenzenesulfonic acid and reaction with anti-trinitrophenyl (TNP) serum as first antibody followed by peroxidase-conjugated second antibody is described. Protein quantities between 1 and 3 ng can be detected in the dot test. This method was used in a double immunodetection procedure after electrophoretic transfer of proteins localizing first a distinct antigen with its specific antiserum followed by visualization of the complete protein pattern on the same blot by the TNP/anti-TNP method as described above. As only water soluble reagents are employed no shrinkage of the membrane occurs. Furthermore, the method can be used in a simultaneous immunodetection procedure visualizing the specific antigen together with TNP marker proteins using a mixture of the specific antiserum and the anti-TNP serum as first antibody. PMID- 4014684 TI - High-performance liquid chromatography of tetrahydro-beta-carbolines extracted from plasma and platelets. AB - A fast method for extraction and concentration of tryptamine (TA), 5-hydroxy-TA, and 5-methoxy-TA was developed using reverse-phase C-18 sample preparation columns in combination with an ion-pairing reagent. Using this method, 1,2,3,4 tetrahydro-beta-carboline (THBC), 6-hydroxy-THBC, and 6-methoxy-THBC, the respective reaction products formed after reaction of formaldehyde with the primary amines mentioned above, and beta-carboline (BC, norharman) and 1-methyl beta-carboline (1-Me-BC, harman) could also be extracted from human and rat platelets and platelet-poor plasma (PPP). A HPLC method combined with fluorometric detection was developed for the quantitative determination of these compounds in the picomole range. The formation of beta-carbolines during the extraction procedure was below the limit of detection of the assay procedure. 6 OH-THBC, THBC, 1-Me-BC, and 5-HT were identified as normal constituents of human platelets, whereas only 5-hydroxytryptamine (5-HT) and 6-OH-THBC could be identified in human PPP. In rat platelets and PPP 5-HT, but no THBCs, could be detected. PMID- 4014685 TI - A simple and sensitive method for monitoring drug-induced cell injury in cultured cells. AB - A simple, sensitive method has been developed for evaluating cell injury noninvasively in monolayer cells in culture. The cell ATP pool was radiolabeled by incubating the cells with [14C]adenine. The uptake and incorporation of [14C]adenine was shown to proportional to the number of cells. As determined by HPLC, about 65-70% of the incorporated 14C label was in the ATP pool, 15-20% was in the ADP pool, and the rest was in the 5'-AMP pool. When prelabeled cells were exposed to toxic drugs (acetaminophen, calcium ionophore A-23187, or daunomycin) there was a marked decrease in cell ATP with a concomitant increase in leakage of labeled nucleotides, mainly 5'-AMP and 5'IMP. We have shown that leakage of 14C label into the medium from the prelabeled cells may be employed for quantitation of cell injury. This new measure of toxicity was shown to correlate very well with LDH leakage from the cells, which is a well accepted measure of cell injury. The leakage of 5'-[14C]AMP also correlated very well with the reduction of cell ATP in cardiac myocytes. This method has been used for monitoring drug-induced toxicity in liver cells, cardiac myocytes, and LB cells. PMID- 4014686 TI - A radiometric assay for determining the incorporation of L-canavanine or L arginine into protein. AB - Procedures for a radiometric assay of L-[guanidinooxy-14C]canavanine were developed which provide a convenient and accurate measure of the incorporation of [14C]canavanine into de novo-synthesized proteins. These methods are also applicable to determining [14C]arginine incorporation into protein. These procedures have been employed to study the synthesis of L-[guanidinooxy 14C]canavanine- and L-[guanidino-14C]arginine-containing proteins from the hemolymph of Manduca sexta and Heliothis virescens, two highly destructive insect pests. PMID- 4014687 TI - Analysis of trimethylselenonium ion in urine by high-performance liquid chromatography. AB - A rapid and simple method for the separation of trimethylselenonium ion and other cationic forms of selenium in urine by HPLC on a strong cation exchanger is described. Most of the inorganic salts in urine are removed prior to chromatography by means of ethanolic precipitation, thus minimizing interferences. Following sample loading and elution with 0.003 M ammonium phosphate (pH 4), a linear gradient to 0.33 M ammonium phosphate (pH 4) is employed. Complete separation of the trimethylselenonium ion from four other selenonium compounds was achieved, and good recovery of the compounds was obtained for the desalting and chromatographic procedures. The procedure was successfully employed to demonstrate that dimethylselenocysteineselenonium iodide and Se-methylselenomethionineselenonium iodide are extensively metabolized when administered to rats, and that trimethylselenonium ion is a major urinary metabolite of both compounds. PMID- 4014688 TI - Liquid chromatographic determination of free and conjugated 3-methoxy-4 hydroxyphenylethylene glycol with wide-ranging substances related to monoamine metabolism. AB - A simple and sensitive procedure was developed for the simultaneous determination of substances metabolically related to monoamine transmitters including 3-methoxy 4-hydroxy-phenylethylene glycol (MOPEG) in dissected brain regions of rats using high-performance liquid chromatography combined with electrochemical detection. The tissue sample was homogenized in HCl solution. The homogenate was divided into two portions, of which one was used for the assay of MOPEG after enzymatic hydrolysis with sulfatase. A butanol extraction process was performed on the remaining portion to obtain the sample of monoamine transmitters, precursor amino acids, and acidic metabolites. The monoamines and precursor amino acids were finally recovered in HCl solution, while the acidic metabolites shifted into the alkaline buffer from the organic layer. The basic and neutral substances were separated with a 0.1 M sodium citrate/citric acid buffer system (pH 4.0) containing 1% tetrahydrofuran, and the acidic ones with 0.075 M sodium citrate/citric acid buffer (pH 3.5) containing 1% tetrahydrofuran, 10% methanol, and 12% acetic acid. The steady-state concentrations of three monoamine transmitters (noradrenaline, dopamine, and 5-hydroxytryptamine) were determined together with their precursors and metabolites. Changes in the concentrations of these substances were examined for various drugs, of which the effects had been previously confirmed. The changes reflected putative drug effects and demonstrated that the procedure was applicable to the regional determination of monoamines and their metabolically related substances. PMID- 4014689 TI - A high-performance liquid chromatographic procedure for the purification of mouse monoclonal antibodies. AB - High-performance liquid chromatography was applied to the purification of monoclonal antibodies from mouse ascites fluid. The method was based on anion exchange chromatography using a TSK DEAE-5PW column and a gradient elution with 20 mM Tris, pH 8.5, and 20 mM Tris, pH 8.5, containing 2.0 M sodium acetate. The method can be applied to analytic or preparative scale separations. Purified immunoglobulins were isolated from samples of 20 to 100 microliter containing up to 19 mg total protein. The average recovery of total protein was 89 +/- 12%. Recovery of the immunoglobulins, based on recovery of immunological activity, was quantitative. In addition to separating the immunoglobulins from the other serum proteins, the various classes of IgG were resolved. PMID- 4014690 TI - Brain cerebrosides: preparative purification using a new chromatographic support- magnammsil. AB - A preparative method for isolation and purification of cerebrosides from bovine brain is described. A crude cerebroside fraction is precipitated with ether from a chloroform-methanol extract and purification is achieved by column chromatography on a new column support, "magnammsil." A partial separation of hydroxy and nonhydroxy cerebrosides is achieved. The method is more economical for a large-scale preparation than previously published methods. PMID- 4014691 TI - Assay of beta-glucuronidase in bile following ion-pair extraction of pigments and bile acids. AB - A method for improving the assay of beta-glucuronidase in hepatic and gallbladder bile is described. The method uses ion-pair extraction with N,N,N-triheptyl-1 heptanaminium bromide to remove pigments and bile acids. Conjugated bilirubin, unconjugated bilirubin, and taurine and glycine conjugates of deoxycholic and chenodeoxycholic acids are extracted efficiently from bile by the procedure. The sensitivity of the spectrophotometric assay of beta-glucuronidase in bile using phenolphthalein glucuronide is increased significantly. PMID- 4014692 TI - Comparison of fluorographic methods for detecting radioactivity in polyacrylamide gels or on nitrocellulose filters. AB - The commercial fluorographic enhancers, En3Hance or Amplify, were not as efficient as 2,5-diphenyloxazole (PPO) for detecting radioactively labeled proteins in polyacrylamide gels or on nitrocellulose filters. For most of the X ray films tested, optimal preexposure was essential to obtain maximum sensitivity in fluorography or indirect autoradiography using intensifying screens. The best results were obtained with nitrocellulose by saturating the filters with PPO. The minimum levels of 35S/14C that could be detected on filters by autoradiography or fluorography in a 24-h exposure were 4 X 10(2) or 1 X 10(2) dpm cm-2 respectively. For 3H these levels were, respectively, 20 X 10(3) or 0.5 X 10(3) dpm cm-2. PMID- 4014693 TI - Enzyme-linked coagulation assay: a clot-based, solid-phase assay for thrombin. AB - A new, solid-phase microtiter plate assay for thrombin has been developed, using fibrinogen bound to wells of a microtiter plate and peroxidase-fibrinogen in solution as an indicator system. When small amounts of thrombin are added to the mixture, peroxidase-fibrin and plate-bound fibrin are formed, and the peroxidase fibrin binds to the plate-bound fibrin. The amount of peroxidase-fibrin binding is proportional to the thrombin concentration and time of incubation. Using this assay, thrombin was measured at concentrations as low as 0.25 ng/ml (0.006 nM) in 150 microliter of sample. In the presence of the specific inhibitors benzamidine and D-phenylalanyl-L-prolyl-L-arginine chloromethyl ketone, the thrombin activity is reduced, at relative concentrations of inhibitors consistent with their affinities and mechanisms of action. The enzyme-linked coagulation assay is generally useful as a highly sensitive and convenient alternative to conventional "clot-based" tests of coagulation. PMID- 4014694 TI - Influence of the time of acidification after sample collection on the preservation of drinking water for lead determination. PMID- 4014695 TI - Californium-252 plasma desorption mass spectrometry of cationic, anionic, and neutral dyes. PMID- 4014696 TI - Sample preparation and system calibration for proton-induced X-ray emission analysis of hair from occupationally exposed workers. PMID- 4014697 TI - Saturation effects in gas-phase photothermal deflection spectrophotometry. PMID- 4014698 TI - Photomultiplier gating for improved detection in laser-excited atomic fluorescence spectrometry. PMID- 4014699 TI - Spectrophotometric determination of hydrogen peroxide with titanium 2-((5 bromopyridyl)azo)-5-(N-propyl-N-sulfopropylamino)phe nol reagent and its application to the determination of serum glucose using glucose oxidase. PMID- 4014700 TI - Caffeine-picrylsulfonate liquid membrane electrode for selective determination of caffeine in analgesic preparations. PMID- 4014701 TI - Identification of polycyclic aromatic hydrocarbon metabolites in mixtures using fluorescence line narrowing spectrometry. PMID- 4014702 TI - Pole bias scanner circuit for quadrupole mass spectrometers of early design. PMID- 4014703 TI - Degeneration of the greater splanchnic nerve by operation. AB - By 1 d after unilateral ligation or severance of the greater splanchnic nerve in the rat immediately caudal to the diaphragm, mitochondrial swelling, lysosomal multiplication and an increase in electron density in axoplasm combined to form a debris of axoplasm in unmyelinated fibers, and both shrinkage and disintegration of myelin occurred in myelinated fibers in the distal stump of the nerve operated upon. By 2 d after operation, the nerve had shrunk to 2 third its original diameter, and most of the nerve fibers except for prominent thick myelinated fibers had dissolved into fatty droplets or other bodies, which were phagocytized by Schwann cells. The degenerated parts adjacent to ligation were then completely replaced by many fibroblasts and numerous collagenous fibers, and the ganglion cells which escaped from direct injury by operation, survived with a remarkable number of free ribosomes and many autophagic lysosomes dispersed within their cytoplasms, together with intact axon terminals, while a few myelinated and several unmyelinated fibers also underwent degeneration at the proximal stumpf of the nerve. These facts can suggest not only that centrifugal elements in the greater splanchnic nerve degenerate more drastically and quickly than has been reported hitherto, but also that there are characteristics of centripetal function in a few myelinated and several unmyelinated fibers. PMID- 4014704 TI - Eye enucleation and regeneration of neural retina in axolotl larvae (Ambystoma mexicanum). AB - The eyes of Axolotl larvae were enucleated at stages 30 and 37. Animals with single dorsomedian eyes resulted in the first case (i.e. stage 30). When a piece of pigment epithelium was re-implanted into stage 37 animals at the site of the lesion, limited regeneration was observed when the implant formed a vesicle, but, when the pigment epithelium remained "open" regeneration of the neural retina was extensive. The possible resons for this difference was discussed. PMID- 4014705 TI - Embryopathic effects of ethanol and caffeine in the chick. AB - The combined effects of ethanol (20 and 40%, 0.1 ml/egg) and caffeine (0.5 and 1 mg/egg) on early chick embryos were investigated. After treatment with 0.5 mg caffeine and 20% ethanol at 48 h incubation, teratogenicity was potentiated, but without affecting embryonic growth. Embryotoxic interactions of this nature might account for congenital defects of doubtful etiology. PMID- 4014706 TI - [Light and electron microscopy analysis of the differentiation of oropharyngeal epithelium in Salamandra salamandra (L.) during metamorphosis (Urodela:Salamandridae)]. AB - During metamorphosis the oropharyngeal-epithelium of Salamandra salamandra consists of cells partly with features typical for larvae partly with these characteristic for metamorphosed animals. In the stratum intermedium cells which in larvae develop to secreting non-ciliated pavement cells become precursors of ciliated cells. During this process mucus granulus were discharged and cells develop cilia. Cells of deepe layers stop the production of mucus granules; those granules, which are already present, disintegrate. Furthermore, new types of goblet cells (type 2 and 3 according to Clemen, 1984) arise. Goblet cells of older larvae (typ 1) are to be found nearly unchanged in metamorphosed animals. Older goblet cells degenerate. In the stratum superficiale during transformation of pavement cells to ciliated cells discharge of mucus and ciliogenesis run parallely. Some of the pavement cells, however, degenerate. The stratum basale remains unaltered. PMID- 4014707 TI - Fine structure of epidermal mucous cells of some Brazilian earthworms (Oligochaeta:Annelida). AB - Electron microscopic techniques were adopted to study the comparative morphology of the secretory granules of the epidermal mucous cells of 4 species of brazilian earthworms. 2 main types of secretory granules were described: A first type, presenting a central body with a high electron density and surrounded by a material with variable aspects and electron densities. The second type of secretory granule possesses an homogeneous aspect and a relatively low electron density. The size and the morphology of secretory granules reveal significant variations among the species and also inside a single specie. PMID- 4014708 TI - Morphological observations on the mesodermal cells in the 8 day opossum embryo. AB - Cells of the mesodermal layer of the 8 day opossum were examined by scanning and transmission electron microscopy after removal of the ectoderm. The mesodermal layer is formed by a multilayered network of large somewhat flattened, stellate shaped cells, whose broad surfaces usually lie parallel to the external surface of the embryo. The mesodermal cells show numerous cytoplasmic processes which often appear as long delicate threads that may branch. The processes may course for considerable distances and establish contact with adjacent mesodermal cells. Contact points between processes, processes and cells, and between adjacent cell bodies showed junctional complexes. Most of the junctional complexes appeared morphologically similar to the nexus (communicating) type. Occasional desmosome like junctions also were observed. Extracellular fibers were not observed. PMID- 4014709 TI - [Topography of the infratemporal fossa in the newborn infant]. AB - We compared in our investigations the shape and extent of the infratemporal fossa in newborn, children, and adult specimen. By macroscopical preparation we watched the course of the branches of the mandibular nerve and the maxillary artery and their relations to the masticatory muscles. For identifying of arterial and venous blood vessels the external carotid artery was injected with black ink. In the newborn a fibrous membrane was found coating the internal aspect of the mandibular ramus. The membrane is absent in adults. PMID- 4014710 TI - The use of medial axis transformation to examine evolutionary changes in mandibular shape. AB - Traditional osteometric studies serve to combine both size and shape together, so whether contrasts in mandibular form during recent times reflect predominantly size, or shape, changes remains controversial. In order to examine specific changes in morphological shape, mandibular outline form was subjected to medial axis transformation. This technique was performed on museum mandibles derived from Romano-British, Anglo-saxon and modern (19th century) samples. The lengths of the derived component medial axes, and angles subtended by pairs of medial axes, were subsequently subjected to univariate and multivariate statistical analysis. The data indicated that there were contrasts in mandibular shape between the 3 samples, predominantly reflecting a more vertical ramus, closer approximation between both coronoid and condylar processes with a more prominent mental region in the modern compared with the two older samples. Although the causes of such mandibular changes remain obscure, this study provided objective data on mandibular shape differences in recent times. PMID- 4014711 TI - [Regional differences in the chemical composition of the human tibia]. AB - The chemical homogeneity in all parts of the bone compacta was investigated in 2 human tibiae taken from male cadavers. The ash and nitrogen contents were used as parameters of the chemical homogeneity. Analyses for calcium and phosphorus were performed in addition to characterize the ash content. The mineral components reached their highest levels in the middle of the diaphysis, but the ash contents decline in the directions towards the epiphysis. The distributions of the values for the organic compounds (nitrogen) show a converse pattern. The nitrogen content was highest especially at points where tendons are anchored in the compacta. The ash or mineral content is approximately proportional to the density of the dry bone substance. The chemical composition of the bone compacta can therefore be used to draw conclusions regarding zones that are subject to different functional loads. PMID- 4014712 TI - Experimental morphological studies on the functional role of the pulpal nerves in dentinogenesis. AB - The role of the pulpal nerves in the dentinogenesis of the rat dentition was studied experimentally by means of a time marker of lead acetate and by electron microscope after the individual dissection of the trigeminal and cervical sympathetic nerves or both. Following trigeminectomy, the longitudinal growth of the denervated incisor decreased. Contrary to this, following cervical sympathectomy, the longitudinal growth of the denervated incisor and molar increased 10-5%, and the collagen fibers increased predominantly in the pulpal tissue. The sympathetic nerves seem to play an important part in controlling the differentiation of the odontoblasts, inhibiting the maturation of the growth center of the apical pulp in the continuously developing teeth. PMID- 4014713 TI - Development of the human nervous system in fetuses of Chinese descent--from 80 mm (4 month) to 240 mm CR (end of 7 month gestation). AB - Important regional developments--e.g. histogenesis of areas of cortices, genesis of thalamic nuclei as well as gross morphogenesis remain to be elucidated. The present investigation is an attempt to commence a series of studies to obtain such information. PMID- 4014714 TI - [Mathematical model of the longitudinal growth of long bones]. AB - The specific shape of the long bones is due to a more or less regular increase in length at the level of the epiphyseal plate (Pauwels 1958). This theory assumes, that the epiphyseal cartilage reacts to the local magnitude of stresses. The amount of bone formation is supposed to be proportional to the stress magnitudes. The bone grows straight in the direction of its axis, if the stresses are distributed evenly over the cross-section; but if the stresses increase toward one border of the epiphyseal plate, the bone formation will be stimulated more intensively at this side and consequently the axis of the bone will be bent to the opposite side. By this mechanism, the epiphyseal plate becomes oriented at a right angle to the direction of the stressing force. Pauwels (1958) explains the reorientation of the articular extremities in bones with fractures, consolidated in an angular position by the described reaction. The same reaction is responsible for the formation of the juvenile genu valgum. The genu varum and the so-called coxa vara congenita on the other hand are due to overloading of the epiphyseal cartilage. The described theory has been expressed by a mathematical function and the biological response of the bone has been simulated by means of a computer model. This model explains in a first approximation normal reactions of the growing bone even well as some pathological growth processes. PMID- 4014715 TI - Binucleate cells and liver karyometry. AB - Liver karyometry of uni- and binucleate cells was compared with karyometric measurements excluding binucleate cells in pervinous regions of rat liver parenchyma. Depending on their percentage of the cell population and due to their smaller nuclear size binucleate cells decrease nuclear volume means and the main maximum of frequency distributions of nuclear size (karyometric curves) but increase the lower second maximum in the range of smaller nuclear volumes. The main characteristics of the course of the curves, however, remain unchanged. PMID- 4014716 TI - [Relations of standing height, sitting height and weight of male Americans]. AB - Based on log/log graphs correlating weight with standing and sitting height of U.S. Americans as given by Altman and Dittmer (1962) allometric relations between both heights are tested and found to give relatively good results. With lacking dates of age the standing and sitting heights can only be put in loose time junction by comparison with the length/age tables of Maaser (1974). Approximate relations can be gained between the log weight and standing or sitting height respectively by following a method set up and applied by the author (Sager 1981a, b) with good success. PMID- 4014717 TI - [Fine structure of the fundic gland zone epithelium in various eastern African ruminants]. AB - Light- and electron microscopic investigations were conducted on the epithelium of the area glandulae gastricae propriae of the abomasum, using material of 12 East African game ruminants of nine species. The members of the main feeding categories (Hofmann, Stewart 1972): concentrate selector, roughage eater and intermediate feeder did not differ much in the ultrastructure of the fundic stomach epithelium but showed greater differences with respect to the height and shape of the glandular tubules and the arrangement of the epithelial cell types. Specifically the following cell types were observed: mucoid cells, chief cells, parietal cells, seven different endocrine cells, tuft cells and two types of migrating cells. In some epithelial celltypes of the concentrate selector dikdik, cristalloid cytoplasmic inclusions were found. PMID- 4014718 TI - Myoepithelial cell ultrastructure in the submandibular gland of man. AB - In human submandibular glands, two types of myoepithelial cells can be distinguished in serial ultrathin sections. The dark myoepithelial cell type was stellate in shape and exhibited a pronounced electron density due to numerous myofilaments with focal densities. Dark cell types accounted for the greater part (76%) of the myoepithelial cells and furthermore showed adenosine triphosphatase activity. This type of myoepithelial cell is considered to be that previously observed in mammalian salivary glands. Occasionally, desmosomes could be found between the processes of adjacent dark myoepithelial cell types, which is appropriate with respect to the strong compression of acinar or intercalated duct cells. The light myoepithelial cell type was large and ellipsoid with a few short thick processes, and was characterized by an electron lucent cytoplasm which included scant and unevenly distributed myofilaments. Light cell types showed positive adenosine triphosphatase activity and accounted for only a small part (17%) of the myoepithelial cell number. Transitional forms between these two types were also observed. The light myoepithelial cell type may mature into the dark myoepithelial cell type by means of the transitional form. In addition, clear cells were sometimes encountered between the myoepithelial cell and the acinar or intercalated duct cells. PMID- 4014719 TI - Afferent projections from forelimb muscles to the external and main cuneate nuclei in the cat. A study with transganglionic transport of horseradish peroxidase. AB - Muscular and cutaneous afferents from distal forelimb distributed to the cuneate and external cuneate nuclei have been demonstrated in cat with the method of transganglionic transport of horseradish peroxidase. Injections of the same tracer were also done in ganglia C7 to T6 to demonstrate the afferents to these two nuclei. It is concluded that only muscle afferents terminate in the external cuneate nucleus. Afferents from paw and forearm occupy sequential territories in the medial part of the nucleus, which are only partly exclusive. Afferents from individual flexor muscles of forearm occupy distinct sites but their distributions overlap with those of forearm extensor muscles. In the external cuneate nucleus, the distributions of afferents from individual muscles constitute integral parts of a segmental representation. In the cuneate nucleus, cutaneous afferents are located dorsally and terminate over cells of the "clusters". Muscle afferents are distributed in ventral regions and are topographically arranged. They terminate over "reticular" regions. PMID- 4014720 TI - Large particles associated with gap junctions of pancreatic exocrine cells during embryonic and neonatal development. AB - The formation of gap junctions was studied in pancreatic exocrine cells of rats and mice during late embryonic and neonatal development by the freeze-fracture replica method. Small gap junctions were present in association with tight junctional strands near the cell apex during embryonic development. Independently of tight junctions, small gap junctions were sometimes seen more basally on day 13 to 15 of gestation. The gap junctions increased in number and were rapidly enlarged by day 18 to 20 of gestation. Large particles 12-13 nm in diameter were frequently associated with the gap junction, which consisted of 10 nm particles. The large particles were either irregularly distributed or arranged in hexagonal patterns. The number of large particles decreased with time, so that they sparsely rimmed the gap junction in postnatal animals. This suggests that large particles are precursors of typical gap junctional particles, and that they participate in rapid growth of the gap junction during late embryonic development. It may be also possible that large particles represent functionally different gap junctions. PMID- 4014721 TI - Morphological studies on the role of the periductal stroma in the regression of the human male Mullerian duct. AB - The regression of the male Mullerian duct has been studied in human embryos and fetuses by means of the semi-thin light microscopic technique and by electron microscopy. After completion of the duct's differentiation during week 7, a periductal stroma is formed by two types of mesenchymal-like cells: light, epitheloid cells originating from the coelomic epithelium and dark, fusiform cells of mesonephric origin. During week 9 these cells condense to a compact cuff in which the light cells occupy the inner core. The duct is entirely sealed by an epitheloid stratum of the periductal stroma. At the same time, the basal lamina thickens up to 300 nm by apposition of extracellular material. During weeks 10 to 12, the inner stromal core is invaded by dark fusiform cells from the peripheral stratum which intermingle with the light cells. The basal lamina dissolves, the epithelio-stromal interface becomes indistinct and finally disappears. During week 13 remnants of the Mullerian duct can be observed. They result from the complete merging of the ductal into the periductal compartment. Mullerian duct regression is divided into two functional steps: First the duct is prevented from growth by the epitheloid cells of the stromal cuff. This process lasts for 2 to 3 weeks. In the second place the basal lamina breaks up under the influence of the dark stromal component. This event launches the regression proper and lasts for another 2 to 3 weeks. Necrosis of cells or programmed cell death does not play a decisive role in the regression of the human Mullerian duct. In the upper, nonregressing part of the duct, light epitheloid cells are scarce and do not seal the duct. A periductal extracellular space is preserved during the entire period and the periductal stroma does not fuse with the duct's epithelium. The epithelio stromal interface is maintained along this section. PMID- 4014722 TI - Axonal microtubules: a computer-linked quantitative analysis. AB - Employing current computer-aided morphometric techniques, axonal microtubule density was determined for the rat sural nerve. Analysis of extensive data showed that while microtubule number increases with axon size, the increase is not directly proportional. Thus the relationship between microtubule density and axonal size is inversely related, so that microtubule density is greater in smaller axons than in larger axons. When a proximal and distal site, separated by 2 cm, were compared for microtubule density there was no significant difference, using pooled data for all fibre diameters. The results are interpreted in terms of our present knowledge of axonal-microtubule quantitative relationships, which is reviewed. PMID- 4014723 TI - A quantitative approach to cytoarchitectonics. X. The areal pattern of the neostriatum in the domestic pigeon, Columba livia f.d. A cyto- and myeloarchitectonical study. AB - The areal pattern of the neostriatum of the domestic pigeon, Columba livia f.d., is described in detail. The map was completed with the help of cyto- and myeloarchitectonical studies during which both qualitative and quantitative methods were applied. The map is divided into 16 areas which are characterized in this paper. Most of these areas can be interpreted as being not only structural but also functional units. The areas Ne 1, Ne 7, and Ne 12 represent primary projection fields. The areas Ne 2, Ne 4, Ne 5, Ne 9, Ne 13, and Ne 14 can be regarded as associative areas, closely connected with the primary areas. The areas Ne 6, Ne 11, Ne 15, and Ne 16 are described with regard to a possible integrative function. PMID- 4014724 TI - Nerve growth factor treatment does not prevent dorsal root ganglion cell death induced by target removal in chick embryos. AB - In chick embryos, on the 3rd day of incubation, the developing right wing bud was removed. One group of the operated embryos was treated with a daily dose of 20 micrograms purified nerve growth factor (NGF) from the 5th day of incubation and sacrificed on the 12th day. The other group was sacrificed on the 12th day of incubation and served as control. NGF was also administered to intact, unoperated embryos for comparison. The size of the dorsal root ganglia in segments 13-16 innervating the wings, were estimated and the number of surviving dorsal root ganglion cells counted both on the right (operated) and left (intact) sides. Although NGF brought about an increase in the size of the ganglia and an increase in the number of dorsal root ganglion cells bilaterally, it was not able to prevent excessive cell death of dorsal root ganglion cells on the operated side. The number of surviving neurons in the dorsal root ganglia on the operated side in embryos with or without NGF administration was only about 30-50% of the number of the intact side. These results show that cell death induced by target removal cannot be offset by NGF administration. It is concluded that NGF may act as a growth promoting agent for developing sensory neurons but other peripheral trophic factor/s are also needed for the maintenance and survival of dorsal root ganglion cells. PMID- 4014726 TI - An ultrastructural study of meconium corpuscles in human foetal colon. AB - In human foetal colon meconium corpuscles were observed in the colonic epithelium during the stage of secondary lumina development and enlargement. Transmission electron microscopy of these specimens revealed inclusion bodies in the superficial and deeper layers of the epithelium. Many of the membrane-bounded inclusion bodies contained well-preserved organelles and some inclusions contained nuclear fragments. There was evidence of nuclear fragmentation with condensed chromatin arranged in crescentic caps. The ultrastructural observations are typical of apoptosis, a mode of cell death first described in 1972 by Kerr and colleagues. Thus, meconium corpuscles are apoptotic bodies found as a result of the deletion of healthy normal cells during the reshaping and development of organs. PMID- 4014727 TI - The B.B. Sankey Anesthesia Advancement Award. PMID- 4014725 TI - Ultrastructural localization of type IV collagen and laminin in the seven-day-old mouse embryo. AB - The localization of the basement membrane components type IV collagen and laminin was investigated in seven-day-old mouse embryos (NMRI) fixed with formaldehyde, using an immunoperoxidase technique. Posttreatment of the embryos with TBS (trishydroxymethylaminomethane buffered saline) buffer was prerequisite for restoration of the antigenicity after fixation. The localization of the peroxidase (PO) positive reaction after treatment with anti-type IV collagen and anti-laminin antibodies in the embryos has been compared with results obtained after fixating embryos with the addition of tannic acid. Tannic acid stained the basement membrane of the ectodermal cell layer, in particular the lamina densa. After immunostaining for type IV collagen and laminin, a strong PO-positive reaction in the lamina densa of the ectodermal basement membrane was observed. A basement membrane of the endodermal cell layer had not yet been formed at this developmental stage. In this region, which is where a basement membrane was to develop in later stages, a tannic acid positive material consisting of granules with a diameter of about 25 nm was found near the surface of the endoderm. Moreover, PO-positive patches were seen in this part of the embryo after staining for laminin as well as after staining for type IV collagen. These PO-positive patches were mainly localized in areas where mesodermal cells lay adjacent to the surface of the endodermal cell layer. No positive staining for type IV collagen and laminin was found in the cytoplasm of either ectodermal or endodermal cells. PMID- 4014728 TI - Direct opioid application to peripheral nerves does not alter compound action potentials. AB - The identification of opiate receptors on primary afferent fibers near the dorsal root ganglia suggests that opiates may be able to affect conduction in primary afferent nerve fibers. We examined the effect of directly applied, preservative free morphine sulfate (0.1 mg/kg) and fentanyl citrate (25 micrograms/kg) on the A beta, A delta, and C components of the compound action potential of the superficial radial nerve in decerebrate cats (n = 18). Neither drug caused any significant change in the area under the curve of any of the compound action potentials studied. These data indicate that systemically administered opiates are unlikely to cause changes in primary afferent nerve conduction. PMID- 4014729 TI - The hemodynamic consequences of high-dose thiopental anesthesia. AB - The hemodynamic and electroencephalographic effects of a 60 min infusion of thiopental, given at the rate of 1.25 mg X kg-1 X min-1 (total dose 75 mg/kg), were studied in 10 patients without cardiorespiratory disease undergoing surgery for the removal of large and/or deeply seated arteriovenous malformations. Data on heart rate, arterial, right atrial, pulmonary arterial, and pulmonary capillary wedge pressures, thermodilution cardiac output (expressed as cardiac index), the electroencephalogram, arterial blood gases, and serum thiopental concentrations were collected during a sedated, resting control period, and then every 15 min during drug infusion. Lactated Ringer's solution (total volume 1-2 liters) was infused throughout the study period at rates sufficient to maintain pulmonary capillary wedge pressure at control values. In doses sufficient to render the electroencephalogram isoelectric [t approximately equal to 30 min, 37.5 mg/kg cumulative dose, serum concentration 51 +/- 17 micrograms/ml (mean +/- SD)], drug infusion resulted in significant increases in heart rate (to 116% of control), and decreases in arterial pressure (to 87% of control), stroke volume index (to 87% of control), systemic resistance (84% of control), and both left and right ventricular stroke work indices (66% and 69% of control, respectively). Cardiac index was unchanged (following a transient increase at t = 15 min). There were no changes in pulmonary vascular resistance, or blood gases. A large total dose of thiopental (8-11 gm) was needed to maintain electroencephalogram suppression for the remainder of these 10-20 hr procedures, and emergence was slow (48-72 hr). The resultant prolonged ICU support may have contributed to serious postoperative complications in two patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4014730 TI - Cardiac electrophysiologic effects of pancuronium. AB - A microelectrode examination of guinea pig left ventricular papillary muscle was performed to determine whether there was a direct effect of pancuronium on cardiac cells and, if so, to attempt to ascertain the mechanism of this effect. Electrical events were measured before and during superfusion with pancuronium, epinephrine, propranolol, and verapamil; alone and in various combinations. Pancuronium prolonged the duration of the action potential (AP); increased resting potential (Em), AP magnitude, and rate of rise of the AP (dV/dt); and resulted in spontaneity in 12% of the muscles. Epinephrine and pancuronium combined caused spontaneity in 80% of the muscles and oscillatory behavior. Additionally, this combination decreased AP magnitude, Em, and dV/dt in several preparations--a pattern of response similar to that seen in ouabain-treated myocardial cells under the influence of catecholamines. These changes were always reversed by verapamil or by perfusion with a drug-free medium, and were usually reversed by propranolol. The data suggest a combined pancuronium/epinephrine induced increase in cardiac membrane permeability to Ca2+. PMID- 4014731 TI - Incidence of malignant hyperthermia in Denmark. AB - Questionnaires were sent to all anesthesia departments in Denmark to determine the total number of anesthetics given per year, and the distribution of different types of anesthesia. All cases of suspected malignant hyperthermia forwarded to the Danish Malignant Hyperthermia Register during a 6.5 yr period were reviewed and divided into subgroups according to clinical criteria. The incidence of suspected malignant hyperthermia in these subgroups was calculated in relation to type of anesthesia. The results are based on information about 386,250 anesthetics and 154 cases of suspected malignant hyperthermia. All cases of malignant hyperthermia occurred during general anesthesia, and more than 75% during anesthesia with a combination of potent inhalation agents and succinylcholine. The incidence of fulminant malignant hyperthermia was low: 1 in 250,000 total anesthetic procedures, but 1 in 62,000 anesthetic procedures with a combination of potent inhalation agents and succinylcholine. Masseter spasm occurred in 1 of 12,000 anesthetic procedures in which succinylcholine was administered. Suspicion of malignant hyperthermia was raised in 1 of 16,000 anesthetics total, but in 1 of 4,200 anesthetics with the above-mentioned combination of agents. PMID- 4014732 TI - A retrospective study of the incidence and causes of failed spinal anesthetics in a university hospital. AB - One hundred sequential spinal anesthetic procedures were reviewed retrospectively to study specifically the incidence and causes of spinal anesthesia. Variables examined included the patient population, the technical aspects of performing subarachnoid tap and subsequent blockade, and the level of training of the anesthetists. We found a 17% incidence of spinal failure, defined as the need to use general anesthesia during the surgical procedure. Failure was found to be significantly associated with a lack of free flow of cerebral spinal fluid, the use of tetracaine without epinephrine, and an increased administration of intravenous supplementation. Forty-one% of the failures represented errors in judgement, either in not properly anticipating the duration of surgery or injecting local anesthetic solution in the absence of a free flow of cerebral spinal fluid. An incidental finding was the lack of documentation in many of the variables examined. We attribute the high incidence of failed spinal anesthesia mainly to technical reasons, most of them avoidable. The use of local and regional anesthesia requires considerable technical skills and demands a precise and total understanding of regional anatomic relationships. With the decreasing use of regional anesthesia in our operating rooms, only those regional anesthesia techniques that require minimum dexterity, such as spinal and epidural anesthesia, continue to be utilized widely; and even these techniques, safe as they are, are being poorly taught. PMID- 4014733 TI - Continuous measurement of intravascular pH with a fiberoptic sensor. PMID- 4014734 TI - Sublingual emphysema complicating dental anesthesia. PMID- 4014735 TI - Atomizer modification for nasal administration of cocaine and other drugs. PMID- 4014736 TI - Ventilatory management of massive bronchial hemorrhage by endobronchial high frequency jet ventilation and continuous suctioning. PMID- 4014737 TI - A method for detection of incompetent unidirectional dome valves: a prevalent malfunction. PMID- 4014739 TI - Sensitive measures of outcome. PMID- 4014738 TI - Respiratory insufficiency after gastrostomy prior to tracheoesophageal fistula repair. PMID- 4014740 TI - Anesthesia and analgesia are mediated by different mechanisms. PMID- 4014741 TI - Regional blood flows during induced hypotension produced by nitroprusside or trimethaphan in the rhesus monkey. AB - In monkeys anesthetized with 70% nitrous oxide and 0.5% inspired halothane in oxygen, we measured changes in systemic hemodynamics and regional blood flows produced by nitroprusside and trimethaphan. Regional blood flow measurements were made using the radioactive microsphere technique. Control measurements were made before infusion of nitroprusside and trimethaphan into each animal in sequence in amounts adequate to reduce mean arterial pressure to approximately 55 +/- 5 mm Hg. Measurements were made during each drug infusion after a stable period of hypotension lasting at least 30 min. During nitroprusside infusion, cerebral blood flow remained unchanged, but myocardial blood flow increased significantly. However, pressure-rate product, an indirect measure of myocardial oxygen consumption, was unchanged, implying that myocardial blood flow exceeded myocardial oxygen requirement. During trimethaphan infusion, cerebral blood flow decreased, although cerebral metabolic rate for oxygen was unchanged due to increased oxygen extraction by the brain. Trimethaphan also produced a decrease in myocardial blood flow that was in proportion to the decrease in myocardial oxygen requirement as indicated by pressure-rate product. Neither drug produced changes in renal or total hepatic blood flows. We conclude that brain oxygen reserve is decreased during hypotension induced by trimethaphan. Blood flows to other organs are not significantly impaired in monkeys during hypotension to a mean arterial pressure of approximately 55 mm Hg induced by either nitroprusside or trimethaphan. PMID- 4014742 TI - Antagonism of phase II succinylcholine block by neostigmine. AB - The neuromuscular effect of neostigmine, 1.25 mg/70 kg, was assessed in 40 adult patients 10 min after cessation of a succinylcholine infusion. The patients had received a thiopental-nitrous oxide anesthetic supplemented by halothane or fentanyl during which they were given at least 5 mg/kg succinylcholine over more than 90 min. Train-of-four monitoring was used. Neostigmine accelerated recovery of neuromuscular function in all patients. The degree of recovery was directly related to the train-of-four ratio, and the results in patients who had received halothane were no different from those who had received fentanyl. The findings are compatible with the hypothesis that phase I block depends upon the presence of circulating succinylcholine and decreases as the latter is cleared, whereas phase II block decreases more slowly. Thus succinylcholine block can be antagonized by neostigmine if enough time is allowed for phase I block to disappear and for a pure phase II block to be present. PMID- 4014743 TI - Epidural morphine: a clinical double-blind study of dosage. AB - The purpose of this randomized double-blind study was to determine the optimal dose of epidural morphine by establishing a dose-effect relationship. The 139 patients, who had orthopedic operations on the lower extremities, received continuous lumbar epidural anesthesia with bupivacaine, 0.75%, with or without the addition of 1, 2, 3, 4, or 5 mg of morphine hydrochloride. Analgesia and side effects were determined during the first 24 hr postoperatively. In the 12-hr period after epidural anesthesia, arterial blood gas tensions were compared between those patients who received 5 mg morphine (n = 13) and those who received no morphine (n = 14). Patients who received 2 or more mg of morphine were less likely to require the administration of postoperative systemic analgesics (P less than 0.05). The addition of 2 or more mg of morphine to bupivacaine, 0.75%, reduced postoperative pain intensity (P less than 0.05); 5 mg of morphine reduced pain intensity for the longest time. Frequency of catheterization and pruritus increased dose-dependently. The mean PaCO2 after 5 mg of epidural morphine averaged 5 mm Hg higher than in the control group, indicating minor respiratory depression, better analgesia, or both. The dose of 3 mg of epidural morphine added to the local anesthetic is recommended for postoperative analgesia after surgery of the lower extremity; it is a compromise that provides adequate analgesia with an acceptably low frequency and intensity of side effects. PMID- 4014744 TI - Potentiation of systemic morphine analgesia in humans by proglumide, a cholecystokinin antagonist. AB - Proglumide, a cholecystokinin antagonist, potentiates analgesia produced in rats by morphine and endogenous opiates, and appears to reverse tolerance in rats to opiate analgesia. Therefore, proglumide and other cholecystokinin antagonists may be clinically valuable. We have tested proglumide's possible opiate analgesic potentiating effects by examining, in volunteers, the effects of morphine and proglumide on human pain visual analogue scale responses to 45-51 degrees C skin temperature stimuli. Proglumide (50-100 micrograms intravenously) potentiated both the magnitude and duration of analgesia produced by small doses of morphine. This study provides indirect evidence for a cholecystokinin-opiate interaction in humans. Therefore, cholecystokinin antagonists such as proglumide may serve to potentiate exogenous or endogenous opiate action. PMID- 4014745 TI - Respiratory sinus arrhythmia during recovery from isoflurane-nitrous oxide anesthesia. AB - Heart rate and respiratory patterns were monitored in ten ambulatory female patients undergoing elective laparoscopy. The patients were anesthetized with isoflurane-nitrous oxide. An index of cardiac vagal tone determined from the heart rate pattern by quantifying the amplitude of respiratory sinus arrhythmia was elevated over four 10-min periods: before induction of anesthesia; during maintenance of anesthesia; upon arrival in the recovery room; and 20-30 min later when the patient was fully conscious. All ten patients' vagal tones were lowest during maintenance of anesthesia. During the recovery periods vagal tone increased and approached the conscious level. On-line analysis of respiratory sinus arrhythmia may provide a physiological index of the level of anesthesia and the rate of recovery. PMID- 4014746 TI - Temperature and ventilation after hypothermic cardiopulmonary bypass. AB - Rewarming in the postoperative period after hypothermic cardiopulmonary bypass is often associated with hemodynamic and ventilatory instability. Temperature changes, PaCO2 values, and delivered mechanical ventilation were observed for the first 12 hr in the intensive care unit in 73 patients who had undergone cardiac surgery with hypothermic cardiopulmonary bypass. Mean rectal temperature increased from 34.7 to 38.3 degrees C over the first 8 hr after admission to the intensive care unit (P less than 0.001). The temperature curve was sigmoid rather than linear, and the most rapid rate of temperature increase occurred 2-4 hr after admission. During rewarming, the most common abnormality of PaCO2 on mechanical ventilation was acute respiratory acidosis (PaCO2 greater than 45 mm Hg, pH less than 7.35), which occurred in 42% of patients. This suggests that ventilatory management in the early postoperative period after hypothermic cardiopulmonary bypass should be carefully adjusted to the increased metabolic rate during rapid rewarming. PMID- 4014747 TI - Aminophylline is an antagonist of lorazepam. PMID- 4014748 TI - Hydropneumothorax after percutaneous nephrolithotomy. PMID- 4014749 TI - Closed circuit anesthesia is accurate at any altitude. PMID- 4014750 TI - Epidural anesthesia in patients with spinal fusion. PMID- 4014751 TI - An unusual complication of the Arrow Radial Artery Kit. PMID- 4014752 TI - Valsalva maneuver in pulmonary artery catheterization. PMID- 4014753 TI - Convulsions and ventricular tachycardia from bupivacaine with epinephrine: successful resuscitation--congratulations! PMID- 4014754 TI - Use of neurosurgical patients for muscle relaxant studies. PMID- 4014755 TI - Equilibrium of 1% halothane with components of the central nervous system. PMID- 4014756 TI - Are neuromuscular blocking agents more efficacious in pairs? PMID- 4014757 TI - Persistent phrenic nerve paresis following interscalene brachial plexus block. PMID- 4014758 TI - In support of diffusion barriers about nerve. PMID- 4014759 TI - General anesthesia without O2 analyzer--a substandard practice. PMID- 4014760 TI - Portable semiclosed circuit for prolonged oxygen administration in aircraft. PMID- 4014761 TI - Differentiating interstitial fluid from cerebral spinal fluid. PMID- 4014762 TI - An alternate method to manage patients with protamine hypersensitivity for cardiac surgery. PMID- 4014763 TI - Early detection of malignant hyperthermia. PMID- 4014764 TI - Respiratory monitoring for children undergoing radiation therapy. PMID- 4014765 TI - Failure to withdraw flexible fiberoptic laryngoscope after nasotracheal intubation. PMID- 4014766 TI - Simple charcoal filter for closed circuit anesthesia. PMID- 4014767 TI - Isoflurane-fentanyl flush. PMID- 4014768 TI - Pronounced, episodic oxygen desaturation in the postoperative period: its association with ventilatory pattern and analgesic regimen. AB - The respiratory effects of two postoperative analgesic regimens were compared in two groups of 16 patients each, recovering from general anesthesia and major surgery. One group received a pain-relieving dose of iv morphine (mean, 18.1 mg), with the same dose repeated as a continuous intravenous infusion over the subsequent 24 h. The other group received regional anesthesia using bupivacaine. The patients were monitored for 16 h after surgery. The two analgesic regimens provided patients with comparable analgesia throughout the study period, but there were quite different respiratory effects in the two groups. Ten patients receiving morphine infusions had a total of 456 episodes of pronounced oxygen desaturation (SaO2 less than 80%). These occurred only while the patients were asleep, and all were associated with disturbances in ventilatory pattern, namely, obstructive apnea (144 episodes in eight patients), paradoxic breathing (275 episodes in six patients), and period of slow ventilatory rate (37 episodes in one patient). In contrast, in patients receiving regional anesthesia, oxygen saturation never decreased below 87%. Central apnea, obstructive apnea, and paradoxic breathing occurred more frequently in patients in the morphine group (12, 10, and 10 patients, respectively) than patients in the regional anesthesia group (4, 3, and 5 patients, respectively). The interaction of sleep and morphine analgesia produced disturbances in ventilatory pattern, causing profound oxygen destruction. These results suggest that postoperative pain relief using regional anaesthesia has a greater margin of safety in terms of respiratory side effects than does the continuous administration of opiates. PMID- 4014769 TI - Anticonvulsant actions of enflurane on epilepsy models in cats. AB - The effects of enflurane on three epilepsy models were studied in cats. The models used were seizures in amygdaloid kindled cats and those induced by bicuculline and penicillin. The authors found that not only a subconvulsive (1.5%) but a convulsive (3.5%) dose of enflurane suppressed the seizures in all models. There was no sign of activation by enflurane of the epileptic focal activities in the dose range studied: the penicillin-induced cortical seizure was suppressed completely, and the threshold dose of bicuculline required to induce seizure in normal cats and the threshold current required to induce seizure in amygdaloid-kindled cats were both increased by both the subconvulsive and convulsive dose of enflurane. The pattern of suppression was, however, dissimilar in each model. It was dose dependent in the case of penicillin-induced seizure, while it was biphasic in several aspects in the seizures of bicuculline-induced and amygdaloid kindled models. For the subconvulsive dose the degrees of increase in the thresholds required to induce seizure in bicuculline-induced and amygdaloid-kindled models were both greater than those for the convulsive dose of enflurane. In spite of such a definite suppression of the excitability of focus, the propagation of amygdaloid after-discharge was facilitated by the convulsive dose. The intensity of convulsion induced by suprathreshold dose of bicuculline was depressed in a dose-related manner. The intensity of the convulsion in the amygdaloid-kindled model was also suppressed when it was estimated by visual inspection of behavior and the degree of activation of the brain electrical activities. The authors conclude that there is little, if any, exacerbation by enflurane of preexisting epileptic foci, the only exception possibly being the case of certain myoclonic type epilepsies such as progressive myoclonic epilepsy and photosensitive epilepsy. This anesthetic probably can be used with a considerable degree of safety for epileptic patients. PMID- 4014770 TI - Thiopental pharmacokinetics under conditions of long-term infusion. AB - Thiopental was used in long-term infusion (3-4.5 mg . kg-1 . h-1 during 4-8 days) to protect the brain from injury following trauma. Thiopental plasma concentrations were measured during infusion (48 patients) and after infusion (14 patients) to determine the kinetics of the drug in continuous infusion. All mean values were mean +/- SD. Steady state concentrations (Css) were 31.8 +/- 10.7 mg/l for an infusion rate of 3.05 +/- 0.37 mg . kg-1 . h-1 and 48.9 +/- 14.6 mg/l for a rate of 4.2 +/- 0.3 mg . kg-1 . h-1. Corresponding steady state clearance decreased when Css increased, indicating possible saturation of the metabolic enzymatic system. Michaelis-Menten kinetics were confirmed by postinfusion data that give, for higher Css, a nonlinear decay of log C versus time. First-order kinetics were only obtained with Css below 30 mg/l. The maximum rate of elimination (Vm) was 1.76 +/- 1.15 mg . l-1 . h-1 (n = 11), and the Michaelis constant (Km) was 26.7 +/- 22.9 mg/l (n = 11). Hepatic enzyme saturation was between 35 and 85%. The volume of distribution at steady state was 4.35 +/- 1.83 l/kg (n = 11). Apparent half-lives of elimination were between 18 and 36 h at the end of infusion, and predicted terminal half-lives were 10.15 +/- 5.43 h (n = 11). Phases of burst-suppression were observed on electroencephalographic traces for concentrations greater than 40 mg/l. The authors' results suggest that a continuous infusion at a dose of 4 mg . kg-1 . h-1 induces EEG changes consistent with a near-maximum reduction in cerebral metabolism. Because of the thiopental Michaelis-Menten kinetics at doses above 4 mg . kg-1 . h-1, the authors suggest that thiopental plasma concentrations be measured and/or the drug effect be measured with the EEG to prevent excessive thiopental overdosage, causing a prolonged recovery time. PMID- 4014771 TI - Local spinal cord blood flow and glucose utilization during spinal anesthesia with bupivacaine in conscious rats. AB - The author studied in conscious rats the local spinal blood flow (SCBF) and metabolic effects of intrathecally administered bupivacaine. Fourteen rats received 0.75% bupivacaine, 15 microliters, through a chronically implanted lumbar subarachnoid catheter. Twelve control animals were treated identically, except that they received only an equal volume of saline intrathecally. Ten minutes after intrathecal drug injection, either local SCBF or glucose utilization was measured in the lumbar spinal cord of seven experimental and six control animals with the quantitative autoradiographic iodo-[14C]antipyrine or 2 [14C]deoxyglucose methods, respectively. Intrathecal bupivacaine produced a limp tail, absent hindlimb withdrawal to pinch, and 25-30 min of analgesia on the tail flick test. Mean arterial blood pressure decreased 14% (P less than 0.01) after bupivacaine was administered, but there was no change in arterial blood gases, pH, or rectal temperature. Subarachnoid bupivacaine reduced both local SCBF and glucose utilization, but the SCBF effect was larger. Local SCBF decreased 27-34% (P less than 0.01) in all five spinal gray and three white matter areas measured, and there was little regional variability in the response. The reduction in spinal glucose utilization was regionally selective and less marked. For example, glucose utilization decreased 15% (P less than 0.05) and 21% (P less than 0.05) in lateral and anterior spinal white matter, respectively, but only decreased approximately 3% in laminae I-III and dorsal white matter (P greater than 0.1). A trend toward metabolic depression was also evident in laminae VIII (-15%, P = 0.06), VII (-13%, P = 0.09), and IV-VI (-11%, P greater than 0.1).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4014772 TI - Differential margin of safety of conduction in individual peripheral axons. AB - The relation between fiber size and safety of conduction was tested in vitro on individual afferent axons of rabbit vagus nerve by lowering the external sodium ion concentration and noting the effect on threshold excitability and conduction velocity. Conduction safety of myelinated axons was found to be independent of fiber size and slightly less than among unmyelinated axons. The results are consistent with previous data from the same model, where blocking concentration and diffusion time of lidocaine to the excitable membrane of individual axons also were independent of myelinated axonal size. The evidence from these single unit studies implies that the differential blocks of functional modalities observed with spinal and epidural anesthesia probably do not arise from fiber size-related differences in susceptibility to block: possible alternatives are mentioned briefly. PMID- 4014773 TI - The effect of halothane on drug disposition: contribution of changes in intrinsic drug metabolizing capacity and hepatic blood flow. AB - Several studies have shown that halothane may influence drug disposition in animals and humans, but the mechanism remains unclear. The relative contributions of changes in metabolizing capacity and hepatic blood flow to altered drug disposition were investigated during halothane anesthesia, using propranolol as a model compound. The studies were performed on six dogs on three separate days; first, the day before anesthesia, second, during halothane (2.0 MAC) anesthesia, and third, 24 h after anesthesia. Each dog simultaneously received 40 mg unlabeled propranolol directly into the portal vein and 200 mCi of 3H-propranolol intravenously via chronically implanted catheters. Blood samples were taken every 5 min for the first hour and then every 15 min for a further 3 h for the measurement of unlabeled and 3H-propranolol concentrations. During halothane anesthesia, intraportal-intrinsic clearance was decreased by 62% (P less than 0.05) from 2,110 +/- 298 to 799 +/- 233 ml/min, while systemic clearance was decreased (P less than 0.05) from 470 +/- 33 ml/min preanesthesia to 280 +/- 38 ml/min during halothane anesthesia. The intravenous elimination half-life was increased (P less than 0.05) from 87 +/- 12 to 155 +/- 23 min during anesthesia. Although halothane anesthesia tended to lower liver plasma flow from 642 +/- 80 to 473 +/- 47 ml/min, this change was not significant. The large change in portal or intrinsic clearance indicates that halothane anesthesia markedly inhibits drug metabolizing ability. The authors therefore conclude that the alterations in drug disposition observed during halothane anesthesia are mainly due to inhibition of drug-metabolizing capacity in the liver. PMID- 4014774 TI - An analyzer for in-line measurement of expiratory sulfur hexafluoride concentration. AB - An infrared analyzer for the inert tracer gas sulfur hexafluoride (SF6) is described and evaluated. The analyzer consists of a transducer and a processor unit. It is designed to operate in a nonrebreathing system with a ventilator and a computer. The transducer, which is placed over a cuvette with windows in the ventilator tubings, reads the SF6 concentration in the airway during the expiratory phase. At the end of the inspiratory phase, the zero level of the instrument is automatically reset. The response time and linearity of the analyzer were tested, and interference by other gases was assessed. Full response was reached within 20 ms after a sudden introduction of 0.5% SF6 into the cuvette. The analyzer-computer system had adequate linearity below 0.5% of SF6. Oxygen, nitrogen, and humid air had no influence on the analyzer signal. One hundred per cent nitrous oxide, 4% enflurane, 4% isoflurane, and 4% halothane caused signals corresponding to 0.010, 0.023, 0.022, and 0.043% SF6, respectively. Due to the method for zero reset, the importance of interference from these gases is greatly reduced when inspired and expired concentration approach each other. The disturbance from CO2 (10% CO2 gave a signal corresponding to 0.020% SF6) can be compensated for by including a CO2 analyzer in the set-up. The rapid response and the high sensitivity of the analyzer may make it useful for studies of pulmonary gas mixing and for measurements of lung volume during mechanical ventilation. PMID- 4014775 TI - The hemodynamic response to traction on the abdominal mesentery. PMID- 4014776 TI - Cyanosis and tachypnea with weight loss in an infant. PMID- 4014777 TI - Rhinolaryngoscopy in the allergy office. AB - Rhinolaryngoscopy is a valuable diagnostic and treatment assessment tool for the allergist. We present a method for office use of the rhinolaryngofiberscope and review our experience with 400 consecutive examinations. PMID- 4014778 TI - Intranasal cocaine abuse in an allergists office. AB - Fourteen adults complaining of persistent nasal congestion were found to be recreational cocaine users. All eventually admitted to intranasal drug snorting. None responded to routine nasal therapy. PMID- 4014779 TI - The influence of perennial allergic rhinitis on facial type and a pilot study of the effect of allergy management on facial growth patterns. AB - Perennial rhinitis with an allergic component (PRAC) in association with chronic mouthbreathing has been thought to cause skeletal open-bite facial type and narrow transverse facial dimensions. The object of this study was to supply data for this theory and to determine if allergy management would alter the course of facial growth. When a group of children, aged 5 to 10 years, with PRAC was compared with a matched control sample, a significantly larger palatomandibular angle and lower anterior facial height were found for the PRAC group. Transverse cephalometric measurements showed significantly narrower bilateral orbital breadth, bizygomatic, and binasal dimensions (narrower face) of the PRAC patients compared with the control sample. A pilot study of twelve PRAC patients who received 2 1/2 years of allergy management revealed no significant dento-facial dimensional change. This study suggests that PRAC with chronic mouthbreathing can alter the development of the midface. Whether allergy therapy can prevent or change this is as yet uncertain. PMID- 4014780 TI - Calcium phosphate adjuvanted allergens. AB - Calcium phosphate has been used for many years as an adjuvant for vaccines. Results of field trials using calcium phosphate in several countries have been published and demonstrate high immunogenicity and the absence of untoward reactions. This paper presents preliminary results of studies on the use of calcium phosphate, instead of aluminum compounds, for preparing adsorbed allergens. These were performed with purified house dust, mite, and grass pollen extracts. Immunotherapy with house dust and mite extracts gave a high rate (70%) of satisfactory therapeutic results. Efficacy was compared with immunization carried out with fluid preparations under the same conditions. It was found that satisfactory results were of the same order, but elicited a higher number of injections. Immunotherapy with calcium phosphate adjuvanted allergens was also equal, as with aluminium adjuvanted allergens, according to published data. Good tolerance was noted for adsorbed grass pollen extracts, but clinical evaluation of results can only be reported after treatments during at least three seasons. PMID- 4014781 TI - The occurrence of indoor allergens in Saudi Arabia. AB - Investigations on indoor airborne allergens in Saudi Arabia were performed by mold cultures and dust analyses by counter-current immunoelectrophoresis. Twenty fungal genera were isolated, with Aspergillus as the most often encountered. Most of the dust-bound fungi found are ubiquitous and common. Antibodies against Dermatophagoides pteronyssinus, cat- cow- and rat dander, and Cynodon dactylon pollen were used in the dust analyses. Animal antigens were found in five of the ten dust samples. House dust mites were extraordinarily rare. Pollen of Cynodon dactylon (Bermuda grass) was present in nearly all the samples, and in a concurrent clinical study this antigen was found to be the most common cause of perennial rhinitis. PMID- 4014782 TI - Irritable bowel syndrome and hypersensitivity to food. AB - Food hypersensitivity as a cause of irritable bowel syndrome was investigated by means of exclusion diet and blind provocation. Twelve atopic and twelve non atopic individuals entered into the study. Skin prick testing with 20 foods and food additives and RAST specific for food only, were done in all cases. Serum IgE level was also measured. In 14 patients one or several food or additives were shown to induce the typical symptoms of IBS. In at least nine cases of atopy, an IgE-mediated mechanism could be incriminated. Among other potential pathogenetic mechanisms, the presence in the intestinal tract of yeast (Candida albicans, Geotrichum candidum) seems to be of major importance. Yeast apparently favor the development of allergic as well as pseudo-allergic reactions, at least in some patients. Finally, at least in atopic patients complaining of IBS, it is of importance to search for a food component. Dramatic clinical improvements can result from the introduction of an adequate exclusion diet. PMID- 4014783 TI - Non-allergic bronchial hyperreactivity in asthmatic children decreases with age and increases with mite immunotherapy. AB - Bronchial reactivity to histamine increased 2-fold or greater in six of seven mite-sensitive asthmatic children after mite immunotherapy for 1 year. Bronchial reactivity decreased 2-fold or greater in seven of the eight subjects who received no injections (P = .008). PMID- 4014784 TI - Mononeuritis multiplex and eosinophilia in a patient with asthma. PMID- 4014785 TI - Behavioral strategies and theophylline compliance in asthmatic children. PMID- 4014786 TI - Metered dose inhaler induced bronchospasm in asthmatic patients. AB - Beta-adrenergic agonists in metered dose inhalers (MDIs) are used extensively in the treatment of asthma. Previously we reported that 23 of 1450 (1.6%) of our asthmatic patients experienced immediate bronchoconstriction after using MDI albuterol. In this study we investigated immediate bronchoconstriction after use of MDI-metaproterenol and after placebo-inhaler with "inert ingredients" only. Results suggest that those patients who complained of chest tightness or lack of relief following the use of MDI beta-adrenergic agonists are having true bronchoconstriction. The bronchoconstrictive response is most likely caused by the propellants or the other inert ingredients contained in these MDIs. PMID- 4014787 TI - Migraine: a diagnostic test for etiology of food sensitivity by a nutritionally supported fast and confirmed by long-term report. AB - A diagnostic procedure during a nutritionally supported fast week followed by conventional food sensitivity management achieved major improvement for 80% of a migraine panel. This procedure gave a reliable (0.8 correlation coefficient) prognosis on the substantial value of this approach for selection of the treatment of migraine. The study gave two lines of evidence which indicate that migraine has an etiology of food sensitivity. PMID- 4014788 TI - Severe acute "occupational asthma" caused by accidental allergen exposure in an allergen challenge laboratory. PMID- 4014789 TI - Severe anemia and chronic bronchitis associated with a markedly elevated specific IgG to cow's milk protein. PMID- 4014790 TI - Storage mites culturing, sampling technique, identification and their role in housedust allergy in rural areas in the United Kingdom. AB - Patients with symptoms suggesting housedust mite allergy were tested to storage mites, housedust, and Dermatophagoides spp. Housedust was examined for mites. All patients responded to storage mites. Some were negative to Dermatophagoides. All houses proved to have storage mites in the dust as well as Dermatophagoides, mainly in food stores or pet beds. Storage mites, therefore, are involved in dust allergy. PMID- 4014791 TI - New treatment for ragweed hayfever: polymerized ragweed. PMID- 4014792 TI - Ingestible vegetable antigens for immunotherapy? PMID- 4014793 TI - [What is wrong with your article?]. PMID- 4014794 TI - [Quality of recovery after general anesthesia with isoflurane or halothane]. AB - The quality of recovery and the time required for it were compared in two groups of 20 patients after general anaesthesia with isoflurane or halothane for elective head and neck surgery. The groups were comparable with regard to age, sex ratio, ASA physical status, type of surgery and duration of anaesthesia. After premedication with diazepam and atropine, a standard induction technique was used (thiopentone, succinylcholine), avoiding opiates and sedatives. Maintenance was assured with a mixture of 30% oxygen, 70% nitrous oxide and isoflurane or halothane. The time between the end of administration of anaesthetic drugs and eye opening was 7.15 +/- 2.9 min in the isoflurane group, and 11.0 +/- 4.7 min in the halothane group (p less than 0.01). The differences between the times for the return of spatial and temporal orientation and of mental arithmetic were not significant, though they were clinically clearly perceptible. The patients were less sleepy, livelier and less agitated in the isoflurane group in the first hour of recovery. Recovery was more rapid after general anaesthesia with isoflurane, and of better clinical quality. PMID- 4014795 TI - [Central venous catheterization in pediatric hematology]. AB - Central venous catheters (CVC) have proven to be a reliable route of the administration of chemotherapy, saline, blood cells and nutritional support in patients with malignant haematological disease. However, infection remained one of the most important causes of morbidity associated with this procedure. The aims of this study were a) to evaluate the efficacy of laminar air flow to prevent CVC infections, b) to study morbidity associated with polyethylene (PE) and silicone (S) catheters, and c) to evaluate the part played by increasing staff practice. 177 CVC were inserted in 170 children during a period of 20 months. Ages ranged from 5 months to 15 years (mean: 7 years). All the S CVC were tunnelled whereas, because of their rigidity, none of the PE CVC were. At the time of their removal, bacteriological samples from the CVC skin exit site, blood drawn through the catheter and the tips of these CVC were cultured. During the first period (one year), three groups of CVC were studied: in group 1, 37 S CVC in patients placed in a non-sterile ward; in group 2, 40 S CVC in children nursed under laminar air flow; in group 3, 60 PE CVC in patients of a non-sterile ward. During the second period (8 months), 40 new S CVC were inserted in children nursed in non-sterile wards, but after nursing staff training (group 4).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4014796 TI - [Blood loss and nausea during legal abortion]. AB - The efficiency of oxytocic drugs in therapeutic abortion was studied in 113 women who were randomly assigned to either a control group (n = 44) receiving no oxytocic drugs, a group (n = 36) receiving 0.2 mg ergometrine by slow intravenous injection, or a group (n = 33) given 5 units oxytocin in a intravenous infusion throughout the procedure. The three groups were comparable with regard to the age of patients, the age of pregnancies and parity. The surgical procedure was the same in all three groups and carried out by the same surgeon. General anaesthesia was obtained with an infusion of 500 mg methohexitone and 500 micrograms fentanyl in 500 ml isotonic dextrose solution at a rate of 3 ml X min-1. The anaesthetic requirements were 2.94 +/- 0.80 micrograms X kg-1 fentanyl and 2.94 +/- 0,80 mg X kg-1 methohexitone. The criteria studied were the blood loss as measured by the volume aspired, the presence or absence of nausea and vomiting after the procedure, the age of pregnancy and the total amount of anaesthetic drugs given. No correlation was found between the amount of anaesthetic drugs given and the frequency of nausea and vomiting, and between the amount of blood lost (r = 0.287; ddl = 111; alpha = 17.322). The study did not, therefore, confirm the reputation of oxytocic drugs in reducing the bleeding. It seemed that, in therapeutic abortion, spontaneous uterine contraction was sufficient to control the bleeding. But a significant correlation was found between the amount of blood lost and the age of the pregnancy (r = 0.399; ddl = 111; alpha less than 1%). PMID- 4014797 TI - [Acute renal failure after extracorporeal circulation with aortic counterpulsation in surgically treated patients]. AB - In a series of 604 adults operated on for cardiac surgery with cardiopulmonary bypass (CPB), 21 (3.5%) underwent circulatory assistance by intra-aortic balloon pump (IABP); in 5 of them (24%), acute renal failure (ARF) was observed. ARF occurred in only 26 (4.4%) of the other patients who did not require IABP. Evolution of ARF and its factors were therefore investigated in those patients having received IABP. ARF was defined as serum blood urea nitrogen (BUN) greater than or equal to 16 mmol X 1(-1), urinary urea/BUN less than 10, creatinine clearance less than 40 ml X min-1 X 1.73 m-2. Some perioperative features were compared between patients with postoperative ARF and those without ARF. ARF occurred in the 5 patients with IABP during, or immediately after, weaning from IABP. ARF was more frequent in patients operated on for mechanical complications of myocardial infarction with a significant more severe haemodynamic status. They had significantly longer CPB and aortic clamping times. The prognosis depended on the cardiac failure and not on the ARF. In patients with mechanical complications of infarction, early IABP seemed to be the predominant preventive measure. Other therapeutic implications are suggested, particularly the use of dopamine (1 to 3 micrograms X kg-1 X min-1) because of its renal vasodilating action which can contribute to the maintenance of urinary flow. PMID- 4014798 TI - [Hemostasis and thrombosis in the preoperative period. Practical management]. PMID- 4014799 TI - [Pleural clot ablation and fibrinolytic agents]. AB - Two patients presenting with an important intrapleural clot with cardiorespiratory repercussions were given in situ thrombolytic treatment after drainage with a suction tube had failed. The first patient was treated immediately after thoracophrenolaparotomy for hepatic surgery. Dissolution of the clot was obtained with two local injections of urokinase (450,000 IU). The second patient was treated on the tenth day of a recurring post-traumatic clot, with urokinase (75,000 IU, then 225,000 IU) each day. In addition, this patient received lys-plasminogen locally (15 mukat, then 30 mukat). Dissolution of the clot was complete within five days. Clinical tolerance was excellent and there was no effect on the usual clotting studies. This study confirms previous findings, and underlines the usefulness of this method and its lack of adverse effects, even immediately postoperatively. PMID- 4014800 TI - [Circulatory arrest in the operating room in a patient with a congenital long QT syndrome]. AB - Reversible cardiocirculatory arrest was observed during orthopaedic treatment of a digital dislocation in a 37 year old female patient. Cardiological studies showed a prolonged QT interval (0.6 s) in the patient and her daughter, associated with hypokalemia (3.4 mmol) in the former. The diagnosis suggested was that of Romano-Ward's syndrome. Preparation and choice of anaesthesia are discussed. PMID- 4014801 TI - [Massive traumatic hemoptysis]. AB - A case is reported of a patient who suffered a rupture of one lung as result of thoracic trauma. This gave rise to respiratory distress with massive haemoptysis which was initially treated with a double-lumen endotracheal tube, with separate lung ventilation, a chest drain and massive transfusion. A haemostatic pneumonectomy had to be performed because of the persisting and profuse bleeding. PMID- 4014802 TI - [Percutaneous catheterization of the deep brachial vein]. AB - 50 attempts of deep percutaneous antecubital catheterization are reported. A tourniquet was applied to the upper arm and the medial deep brachial vein was punctured in a point immediately medial to the brachial artery, in the antecubital fossa. Venepuncture was successful in 88% of the cases (44 cases), catheterization possible in 72% of the cases (36 cases). The catheter reached the central venous compartment in 60% of the cases (30 cases). The only benign complication was injury to the brachial artery in 6 cases. Mean duration of catheterization was 20 days. This very easy and safe technique can be used when superficial veins are unusable and use of the deep central veins dangerous or impossible. PMID- 4014803 TI - [Temporary registration of cases of peranesthetic malignant hyperthermia in France]. PMID- 4014804 TI - [General anesthesia for cesarean section. Myths and realities]. PMID- 4014805 TI - [Gas leakage on a respirator]. PMID- 4014806 TI - [Spinal anesthesia in elderly subjects for orthopedic surgery]. PMID- 4014807 TI - [An easily improvisable pneumatic transfusion accelerator]. PMID- 4014808 TI - The effectiveness of calcium chloride in refractory electromechanical dissociation. AB - The effectiveness of calcium in electromechanical dissociation (EMD) has been challenged. Retrospective studies have been contradictory. To determine its effectiveness a prospective, randomized, blinded study comparing calcium chloride and saline in refractory EMD was carried out in the pre-hospital setting from October 1982 to October 1983. Only patients who had received epinephrine and bicarbonate and were refractory were entered in the study. All trauma and pediatric arrests were excluded. Ninety patients presented in refractory EMD. Overall, eight of 48 who received calcium were resuscitated successfully in the field; two of 42 who received saline were resuscitated successfully (P less than .07). A successful resuscitation was defined as the conveyance of a patient with a pulse and a rhythm to an emergency department. Patients were analyzed for age, sex, and witnessing of arrest. There was no statistical difference in demographic data. When the group of EMD patients was broken down into subgroups based on the width of QRS, it was noted that patients with a QRS width less than 0.12 did not respond to calcium, whereas the successfully resuscitated in the group with widened QRS or ischemic changes (N = 70) was eight of 39, compared with one of 31 not receiving calcium (P less than .028). Only one patient who was resuscitated successfully was discharged from the hospital alive. Calcium has been shown to be effective in the cardiac resuscitation of patients in refractory EMD. There may be a subset of patients with widened QRS complexes or ischemic changes who will benefit to a greater extent from the use of calcium chloride. PMID- 4014809 TI - Ionized calcium during CPR in the canine model. AB - The purpose of our study was to determine ionized calcium levels during cardiopulmonary resuscitation (CPR). Following placement of ascending aortic catheters in 15 adult mongrel dogs, ventricular fibrillation was induced electrically. After five minutes without therapy, mechanical external CPR was instituted. Animals received either standard CPR (S-CPR, n = 8) or simultaneous compression and ventilation CPR (SCV-CPR, n = 7) for 30 minutes. Ionized calcium levels were obtained prior to fibrillation and every five minutes during CPR. Mean ionized calcium levels during CPR (1.27 +/- 0.06 mmol/L) did not differ significantly from prearrest levels (1.27 +/- 0.07 mmol/L) at any point during CPR. This was true when the dogs were analyzed together (P = 0.1293) and when the animals receiving S-CPR (P = 0.4465) and SCV-CPR (P = 0.5470) were analyzed by groups. Defibrillation was attempted in all animals and resulted in electromechanical dissociation in three. None of these dogs was hypocalcemic either prior to arrest or during CPR, and none developed an effective rhythm with the administration of calcium. Furthermore, three of the four animals receiving calcium developed markedly elevated ionized calcium levels. Hypocalcemia apparently does not occur during CPR. The beneficial effect of calcium in reported cases cannot be explained routinely by correction of hypocalcemia. Further studies are needed to define the role of calcium administration, if any, in CPR. PMID- 4014810 TI - Antishock trousers: a comparison of inflation techniques and inflation pressures. AB - Ten healthy male volunteers were studied to compare the effects of simultaneous versus sequential inflation of antishock trousers (AST) and simultaneous inflation pressures of 20, 40, and 100 mm Hg on blood volume displacement centrally. Radioisotope scans were used to determine the change in blood volume distribution with various inflation methods and inflation pressures of the AST. Our data suggest that the minimum inflation pressure that displaces blood centrally is 40 mm Hg, and that higher inflation pressures displace a greater percentage of the total blood volume to the central circulation than do lower pressures. The difference is small, however, and probably has no clinical effect. No difference was suggested between simultaneous and sequential inflation. PMID- 4014811 TI - Blood volume distribution in the Trendelenburg position. AB - The Trendelenburg position is used frequently in treating hypotensive patients. It is believed that placing patients in the Trendelenburg position causes an autotransfusion of blood to the central circulation. No published studies document the volume of blood displaced centrally. In our study ten volunteers were placed in the Trendelenburg position. Blood volumes were determined from body surface area, and radionuclide scanning was used to determine blood volume distribution. Placing normovolemic volunteers in the Trendelenburg resulted in a 1.8% (median) displacement of the total volume centrally. The autotransfusion of blood produced by the Trendelenburg position is small and is unlikely to have an important clinical effect. PMID- 4014812 TI - Blunt chest trauma and suspected aortic rupture: reliability of chest radiograph findings. AB - The chest radiographs of 86 patients with suspected aortic rupture from blunt chest trauma were reviewed. Seventy-three patients had no evidence of aortic rupture on aortography or surgical exploration, and 13 patients had surgically confirmed rupture. Sixteen radiographic findings were analyzed for sensitivity and specificity in detecting aortic rupture. The following findings were not statistically significant: hemothorax on either side; rib fractures on either side; pneumothorax on either side; lung contusion; widened left paravertebral stripe; and widening of the mediastinum, along with an increased ratio of mediastinal width to chest width. The most helpful findings leading to suspicion of aortic rupture included nasogastric tube or tracheal deviation to the right at the T4 level; depression of the left mainstem bronchus; and loss of the aortic contour or knob and left apical cap. False positives and false negatives occurred with each radiographic sign, indicating that there is no single finding that is absolutely reliable in predicting or excluding significant injury in every patient with suspected aortic rupture. Analysis of combinations of findings found that when the aortic contour and knob are normal and the nasogastric tube and trachea are not deviated, there was no case of aortic rupture in four consecutive years of experience. These four signs can be used to exclude aortic rupture. PMID- 4014813 TI - Coagulation abnormalities in traumatic shock. AB - Coagulation abnormalities can pose a threat to hemorrhaging patients and to attempts at surgical correction. We have shown that 97.2% of our 180 patients who died of trauma had evidence of coagulation defects prior to fluid or blood treatment. Twelve of 180 patients could not be cross-matched due to inability of their blood to coagulate in the tube. Clinically 50% of these patients had excessive oozing from venipuncture sites, and 28% had excessive hematoma formation not associated with vascular injury. The most frequently abnormal test was the prothrombin time, in 97% of patients followed by platelet count in 72%, and partial thromboplastin time in 70%. The greatest degree of coagulation abnormality occurred in patients with head trauma, followed in decreasing order by gunshot wounds, blunt trauma, and stab wounds to the body. Because 97.2% of the patients had abnormal coagulation studies prior to fluid and blood replacement, this abnormality most likely was due to disseminated intravascular coagulation. We propose using the tube-clot test to give a rapid indication of coagulation in traumatized patients while awaiting laboratory test results. PMID- 4014814 TI - Advanced prehospital care for pediatric emergencies. AB - During an 18-month study period, the mobile intensive care unit (MICU) in Jerusalem responded to 307 pediatric emergencies, representing 5% of the total MICU case load. The most common medical problems were seizures, diagnosed in 100 cases (32%), and conditions related to trauma, diagnosed in 77 cases (23%). Forty one cases (13%) were cardiac arrests. Nineteen patients were pronounced dead with a resuscitation attempt; resuscitation was attempted in 22 patients. Four patients were stabilized for admission to the hospital, but there were no long term survivors. Eighteen cardiac arrest patients (82%) were found in asystole, and most had previous serious medical problems. Based on our experience children are less likely to require or benefit from advanced levels of prehospital care compared to the adult population. When resources for advanced care are limited, priority should be given to adult emergencies. PMID- 4014815 TI - The psychological impact of disaster on rescue personnel. AB - Seventy-nine rescue, fire, and medical personnel and police officers who treated victims of an apartment building explosion completed a questionnaire describing their emotional and coping responses to the disaster. Eighty percent had at least one symptom of posttraumatic stress disorder (PTSD). Eight of 21 PTSD symptoms were present in at least 10% of respondents. The most frequently reported symptom, intrusive thoughts about the disaster, occurred in 74% of those working with or searching for victims at the disaster site. On-the-scene rescue workers had significantly more (P less than .02) PTSD symptoms than did inhospital staff. Fifty-two percent of the respondents reported that family members and coworkers were supportive or very supportive in meeting their emotional needs following the disaster; 36% noted that support networks were not helpful. The coping behaviors most frequently used were to remind oneself that things could be worse (57%) and to try to keep a realistic perspective on the situation (53%). Eleven percent reported seeking emotional support from others or looking to others for direction. Emergency workers responding to a contained, small-scale disaster are likely to experience mild stress responses. Planning for the emotional aspects of these events is needed. PMID- 4014816 TI - CPR training in the community. AB - To provide a profile of potential rescuers of cardiac arrest victims, 1,271 randomly selected subjects were interviewed by telephone. Thirty-nine percent had formal instruction in cardiopulmonary resuscitation (CPR), 90% knew the emergency telephone number (911), and 5% had performed CPR. Subjects with training were significantly younger than those without (36 vs 48 years old) (P less than .001), and they had a lower incidence of known heart disease in family members (7% vs 15%) (P less than .001). More men than women were trained in CPR (44% vs 37%) (P less than .015). We recommend that efforts be undertaken to reach target groups of middle-age and older women for CPR training, and that physicians assume an active role in encouraging families of cardiac patients to learn this procedure. PMID- 4014817 TI - Organization structure and the performance of hospital emergency services. AB - A comparative study of 30 hospital emergency departments (EDs) and nearly 1,500 individuals associated with them was conducted. Data were obtained from institutional records, physicians, patients, and other sources. The object was to investigate the relationship between the organization and performance of these health service systems. The study assessed the quality of medical care, the quality of nursing care, and the economic efficiency of hospital EDs. The results show substantial interinstitutional differences in these criteria. They also show a significant relationship between medical and nursing care, but not between the quality of care and economic efficiency. Differences in ED performance are related to medical staffing patterns, medical teaching affiliation, personnel training, scope of emergency services, number of patient visits processed, and hospital size and complexity. Not all of these variables, however, correlate positively with all three criteria of performance, nor are they equally important to each. PMID- 4014818 TI - Medicolegal management of the organically impaired patient in the emergency department. AB - When the organically impaired patient refuses an indicated treatment or admission, the physician may be subject to legal liability regardless of the action taken. He may be held responsible for a negligent discharge, yet be accountable for charges of battery and false imprisonment should he treat against the patient's wishes. A description of the types of patients involved, an analysis of the basic legal issues, a guide to the assessment of these patients, and recommendations for medicolegal management are presented. PMID- 4014819 TI - Nursemaid's elbow: a radiographic demonstration. AB - Three children aged 13 to 15 months had been pulled by the wrist. Subsequent pain and limitation of motion were typical of nursemaid's elbow. On radiographs, a line drawn through the longitudinal axis of the radius failed to bisect the humeral capitellum as is normally seen. Both the symptoms and the radiographic abnormalities resolved after successful manipulative reduction. PMID- 4014820 TI - Cricoarytenoid arthritis presenting as cardiopulmonary arrest. AB - We describe a patient with a long history of rheumatoid arthritis who presented in full cardiopulmonary arrest. He was given intracardiac epinephrine. Fibroptic laryngoscopy determined the cause of the arrest to be upper airway obstruction from cricoarytenoid joint ankylosis, a complication of long-standing rheumatoid arthritis. The patient underwent a tracheostomy, recovered uneventfully, and was doing well nine months later. The literature is reviewed, and the pathophysiology, clinical findings, presentations, and treatment of this potentially fatal entity are described. PMID- 4014822 TI - Wound ballistics. PMID- 4014821 TI - Salter fractures classified. PMID- 4014823 TI - Emergency medical services at the 1984 Democratic National Convention. PMID- 4014824 TI - Administering endotracheal medication. PMID- 4014825 TI - Effects of furosemide on the racing times of horses with exercise-induced pulmonary hemorrhage. AB - In 3 groups of horses with exercise-induced pulmonary hemorrhage (EIPH), comparisons of racing times and finishing positions were made between the 5 races before the horses were given furosemide and 5 races after furosemide administration. The horses were grouped according to 3 methods used to diagnose EIPH: group 1, observation of hemorrhage at the nostrils within 1 hour after a workout or race; group 2, observation of pulmonary hemorrhage only by endoscopic examination after a race or workout; and group 3, observation of hemorrhage at the nostrils during a race or immediately after a race. Group 4 horses were randomly selected horses running during the study period and were not given furosemide. The statistical method was analysis of covariance and the dependent variable was horses' time per distance. The study compared the 4 groups of horses, using the estimated value of the horses (less than or equal to +10,000 or greater than +10,000), and the horses' interaction in races 1 through 5 before and races 6 through 10 after furosemide treatment. The horses' times were adjusted by the relevant covariates, distance, track variant, and winning time per distance. Significant changes in horses' time per distance were not noticed when comparing values from races 1 through 5 with those in races 6 through 10 in group 1 horses.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4014826 TI - Intravenous histamine administration in ponies with recurrent airway obstruction (heaves). AB - Pulmonary function and airway reactivity to IV histamine were measured in a group of ponies with a history of recurrent airway obstruction (heaves) and their age-, weight-, and gender-matched controls. Ponies were studied during a period of clinical remission (period A), after exposure to a barn environment (period B), and twice during a 2-week recovery phase (periods C and D). At periods A, C, and D, PaO2, dynamic compliance (Cdyn), pulmonary resistance, tidal volume, respiratory frequency, and the log dose of histamine required to reduce Cdyn to 65% of base-line value (log ED65Cdyn) of principals and controls did not differ. Barn exposure (period B) decreased Cdyn, PaO2, and ED65Cdyn and increased pulmonary resistance in principals but not controls. The slope of the histamine dose-Cdyn response curves was not different between principal and control groups of ponies and was unaffected by barn exposure or return to pasture. There was a poor correlation between ED65Cdyn and indices of airway caliber. During acute airway obstruction, ponies with a history of heaves were hyperreactive to IV histamine, but during disease remission, airway response to histamine was not different from that of control ponies. Seemingly, hyperreactivity in principal ponies after exposure to a barn environment cannot be explained solely by alterations in base-line airway caliber. PMID- 4014827 TI - Impact and shear resistance of turf grass racing surfaces for Thoroughbreds. AB - The 2 dominant processes involved in the horse hoof-to-racing surface interaction are the shock loading of the horse's leg upon impact with the racing surface and rotation of the horse's hoof into the racing surface. These processes were measured as impact resistance (ie, the peak deceleration of a moving body upon impact with the test surface) and as resistance to shear. The objective of the present study was to measure physically (under a variety of conditions) those soil and turf factors related to the 2 processes. It was concluded that thatch accumulation and mowing height of the turf did not have a significant (P less than 0.05) effect on racing surface hardness (therefore, turf management should optimize turf growth and recovery), that turf roots were responsible for an increase in impact resistance and in resistance to shear, that control over soil moisture through irrigation and drainage allowed modification of racing surface hardness, and that soil materials tend to have lower impact resistance (ie, lower shock loading of the horse's leg) and higher resistance to shear (ie, greater resistance to hoof rotation) than do sand materials. PMID- 4014828 TI - Base excess as a prognostic and diagnostic indicator in cows with abomasal volvulus or right displacement of the abomasum. AB - The case records of 102 cows with abomasal volvulus and 71 cows with right-side displacement of the abomasum (RDA) were examined to determine whether the preoperative base-excess concentration of the extracellular fluid could be used both as a prognostic indicator for post-operative recovery in cattle with abomasal volvulus and as an aid in differentiating between abomasal volvulus and RDA. The survival rate of cows with abomasal volvulus decreased as the base excess concentration decreased (P = 0.08); the lowest survival rate was observed in cows with base excess less than or equal to -0.1 mEq/L. There was a significant difference (0.01 less than P less than 0.025) among base excess ranges between abomasal volvulus and RDA. All cows with preoperative base-excess concentrations less than or equal to -5.0 mEq/L had abomasal volvulus, rather than RDA. PMID- 4014829 TI - Effects of experimentally induced Pasteurella haemolytica pneumonia on the pharmacokinetics of erythromycin in the calf. AB - Pneumonic pasteurellosis was produced experimentally in 3- to 4-month-old Holstein bull calves by bilateral intrapulmonary administration of 5 X 10(7) to 10(9) colony-forming units of Pasteurella haemolytica. Of 8 calves, 4 developed minor pulmonary changes, 1 died of an apparent bacteremia within 24 hours, and 3 developed extensive pneumonic changes. At 1 week before (1 dose) and at 48, 60, and 72 hours (3 doses) after Pasteurella administration, the calves were given erythromycin at a dosage of 15 mg/kg, and the pharmacokinetic values were determined. There were statistically (P less than or equal to 0.05) significant increases in the distribution and elimination rates associated with pneumonia. The elimination half life decreased from 132.7 +/- 9.6 minutes in prepneumonic calves to 111.1 +/- 13.8 minutes and 99.7 +/- 2.6 minutes in calves with minor and with moderate pneumonic changes, respectively. There also was a decrease in apparent volume of distribution with pneumonia. Erythromycin tissue concentrations were determined 2 hours after the last dose was given to the calves with pneumonia. Tissue concentrations in the pneumonic lung areas were as high or higher than those in nonaffected lung tissues in the same animals. Because of the increased rate of elimination from serum in pneumonic calves, it may be advisable to use shorter dosage intervals in calves with severe respiratory tract disease. PMID- 4014830 TI - Treatment of acute ocular Moraxella bovis infections in calves with a parenterally administered long-acting oxytetracycline formulation. AB - Acute ocular Moraxella bovis infections were induced in the UV-irradiated eyes of 10 calves. Eight calves developed corneal ulcers in at least 1 eye and were used for the treatment experiment. One randomly selected group of 4 calves with corneal ulcers and M bovis infections in 7 eyes was given a long-acting oxytetracycline formulation in 2 IM dosages of 20 mg/kg of body weight each, 72 hours apart. The other 4 calves with corneal ulcers in 6 eyes and M bovis in all 8 eyes served as nontreated controls. Bilateral ocular cultures were obtained and clinical observations were made daily for 20 days after treatment. After administration of the long-acting drug, new ulcers did not develop in the treated calves, whereas 5 new ulcers developed in the control-group calves during this time. The average durations of increased lacrimation/ulcerated eye were 2 and 12 days after treatment in the treatment and control groups, respectively; the average durations of blepharospasm were 3 and 8 days, respectively. Moraxella bovis was not isolated from any of the eyes of the treatment-group calves for the first 6 days after the antibiotic was administered, but was isolated from 1 eye of 1 treated calf on posttreatment day 7 and daily thereafter, for a total of 14 positive cultures of 160 ocular cultures obtained from the treatment-group calves after treatment. The bacterium was isolated from all eyes and from 144 of 160 cultures from the control-group calves during this time. PMID- 4014831 TI - Accelerated bovine mammary involution induced by infusion of concanavalin A or phytohemagglutinin. AB - Right mammary quarters of dairy cows were infused with concanavalin A (conA) or phytohemagglutinin (PHA) near drying off. Significant changes in milk yield and composition were observed by 24 hours after infusion. In general, conA or PHA treatment resulted in significantly greater compositional changes earlier in the dry period compared with control quarters. As involution progressed, lactoferrin, serum albumin, immunoglobulin G, pH, and numbers of somatic cells increased, whereas citrate and the molar ratio of citrate:lactoferrin decreased. Mammary secretion accumulation at 7 days of involution was significantly lower in treated compared with control quarters. The data indicated that intramammary infusion of conA or PHA near drying off accelerates bovine mammary involution, resulting in elevated levels of natural protective factors. PMID- 4014832 TI - Regional distribution of porcine brain blood flow during 50% nitrous oxide administration. AB - Regional distribution of brain blood flow was examined in 6 healthy nonmedicated swine during inhalation of 50% O2 (+ 50% N2) and at 45 minutes of 50% end-tidal nitrous oxide administration. All animals were surgically prepared 10 to 12 days before the hemodynamic study. Catheters were implanted in the left atrium, ascending aorta, descending aorta, and pulmonary artery. Brain blood flow was determined, using 15-micron diameter radionuclide-labeled microspheres injected into the left atrium. Administration of 50% nitrous oxide markedly increased blood flow in all regions of the brain (except corpus callosum), even though the animals were not excited and the arterial blood pressure, arterial blood-gas tensions, pHa, and cardiac output were not different from respective control values. At 45 minutes of 50% nitrous oxide administration, cerebral, cerebellar, and brain-stem blood flows were 144%, 137%, and 137% of respective control values. It is concluded that 50% nitrous oxide administration caused marked vasodilatation in all regions of the porcine brain. PMID- 4014834 TI - Brain stem auditory-evoked potentials of dogs: wave forms and effects of recording electrode positions. AB - Wave forms of canine brain stem auditory-evoked potentials (BAEP) and the effects of electrode positions on the wave forms were studied as a basis for experimental and clinical use of BAEP recording. The BAEP regularly consisted of 5 waves (I to V) with latencies and polarities similar to those of other species. In some dogs, waves II, III, and IV contained distinct subpeaks (a, b, c). Waves similar to waves VI and VII of other species were recorded in some dogs. With respect to BAEP, no site on the head was electrically inactive and BAEP could be recorded as far caudally as the caudal cervical region in some dogs. Wave I, positive in recordings from the dorsal midline of the calvaria (vertex) underwent polarity reversal and increased amplitude and duration in recordings made from caudal ventrolateral regions of the head (mastoid region). As a result, wave I partially or totally obscured wave II so that the latter could no longer be clearly identified. Waves IIIa and IIIb were differentially affected by moving the recording site, indicating that their generators were spatially separated. Waves IV and V were also affected by electrode site, consistent with previous reports that they have spatially separated generators in other species. In recordings made with vertex electrodes referenced to the mastoid region ipsilateral to the stimulated ear, wave I appeared as a high-amplitude positive peak with onset latency equalling that in noncephalic reference recordings, but with somewhat later peak latency and longer duration. As a result, wave II was partially or totally obscured so that only 4 major peaks were evident in the BAEP. In contralateral mastoid reference recordings, latency to peak of wave I was unchanged; however, amplitude of all waves was reduced and waves IIa and IIb were not as clearly differentiated as they were in noncephalic reference recordings. PMID- 4014833 TI - Effect of hydrocortisone on circulating lymphocyte numbers and their mitogen induced blastogenesis in lambs. AB - The effect of hydrocortisone on the number of circulating lymphocytes and their blastogenic response was studied in 20 feedlot lambs given combinations of 3 treatments: hydrocortisone (25 mg/kg of body weight, 4 times a day, IM), feed changes (100% roughage to 90% concentrate over a 6-day period), and oral inoculation of Pasteurella haemolytica biotype T (10(9) to 10(11) bacteria/day via stomach tube) to develop a model for reproduction of septicemic pasteurellosis. Hydrocortisone caused lymphopenia and inhibited the blastogenic response of peripheral blood lymphocytes to phytohemagglutinin and concanavalin A mitogens. A synergistic effect was observed between hydrocortisone injections and feed changes resulting in higher than expected serum hydrocortisone concentrations and lower circulating lymphocyte counts. Seemingly, stress-induced increases in serum hydrocortisone concentrations cause suppression of the immune response of feedlot lambs. The combined effect of feed changes and stress on the immune response of lambs may explain the role of these 2 factors in the pathogenesis of septicemic pasteurellosis. PMID- 4014835 TI - Xylazine-pentobarbital anesthesia in dogs and its antagonism by yohimbine. AB - Once a week for 4 weeks, 5 dogs were given IM injections of xylazine (2.2 mg/kg of body weight) followed in 10 minutes by IV injections of pentobarbital (14 mg/kg). The resultant duration of anesthesia, absence of pedal reflex, and time from return of consciousness to ambulation were consistent from week to week. The mean times were 137.3, 111.8, and 56.9 minutes, respectively. A second experiment using 5 other dogs was performed to evaluate the antagonistic effect of yohimbine on the anesthesia induced by the xylazine-pentobarbital combination. When yohimbine (0.1 mg/kg, IV) was administered 10, 60, and 120 minutes after the xylazine-pentobarbital injection (given as in the 1st experiment), it abolished or markedly reduced the duration of anesthesia, absence of pedal reflex, and the time from return of consciousness to ambulation. After being given yohimbine, the dogs had a smooth recovery without postanesthetic excitement. In experiment 3, IM xylazine injections caused bradycardia without changing mean arterial blood pressure. Subsequent IV pentobarbital administration abolished xylazine-induced bradycardia for approximately 20 minutes and decreased arterial blood pressure slightly and gradually. Respiration was markedly depressed for the first 20 minutes of xylazine-pentobarbital anesthesia and gradually decreased during the rest of the 50-minute monitoring period. Yohimbine injection at postpentobarbital dosing minute 50 reversed the resumed xylazine-induced bradycardia and relieved other signs of respiratory depression associated with xylazine-pentobarbital anesthesia. The xylazine-pentobarbital combination was safe and effective for inducing and maintaining up to 2 hours of anesthesia in dogs.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4014836 TI - Effects of atropine on xylazine-pentobarbital anesthesia in dogs: preliminary study. AB - The influence of atropine on anesthesia induced by xylazine-pentobarbital administration was studied in 5 dogs. The combination of xylazine (2.2 mg/kg of body weight, IM) and pentobarbital (14.0 mg/kg, IV) caused anesthesia with the duration of absence of the pedal reflex, duration of anesthesia, and the time from return of consciousness to ambulation to be 107.4, 123.4, and 59.2 minutes, respectively. Bradycardia and short-term respiratory depression were observed. An IM injection of atropine sulfate (0.045 mg/kg) did not significantly change the durations of absence of the pedal reflex and of anesthesia, the time from return of consciousness to ambulation, or the pattern of respiration in the anesthetized dogs. The PaO2 increased gradually in both groups; however, atropine caused a marked tachycardia and increased the PaCO2. Fifteen minutes after pentobarbital injection, administration of atropine sulfate caused a slight but significant (P less than 0.01) decrease in arterial pH. Although atropine sulfate antagonized xylazine bradycardia, the data indicated that it may have caused increased respiratory depression in dogs anesthetized with xylazine and pentobarbital. PMID- 4014837 TI - Intracellular locations of dermonecrotic toxins in Pasteurella multocida and in Bordetella bronchiseptica. AB - Location of dermonecrotic toxin (DNT) in the cells of Pasteurella multocida or Bordetella bronchiseptica was investigated. After cell lysis by various procedures, various fractions prepared from bacterial cells grown in liquid culture media were assayed for dermonecrotic activity by skin testing of guinea pigs. During the death phase of the growth tested for the 2 bacterial species, little cell-free DNT was detected in the culture supernatants. Throughout the log and stationary phases of the growth, DNT activity was cell associated, but was not seen in the culture supernatants, which indicated that DNT was not secreted by actively growing P multocida or B bronchiseptica cells. Little DNT was released by subjecting whole cells to osmotic shock, a common procedure that releases proteins from the periplasmic space of many gram-negative bacteria. After sonication and centrifugation of whole cells, a substantial amount of DNT was released; results were similar when spheroplasts were used instead of whole cells. Treatment of whole cells with trypsin did not decrease the DNT activity, but trypsin treatment of sonicated cells resulted in a significant decrease in the DNT activity (P less than 0.01). The results indicated an intracellular location of the DNT of P multocida or B bronchiseptica. The DNT of P multocida or of B bronchiseptica is probably located in the cytoplasmic space. PMID- 4014838 TI - Serologic studies of bovine respiratory syncytial virus in Minnesota cattle. AB - Serum antibody titers to bovine respiratory syncytial virus were determined for 559 cattle. Serum samples were obtained through the Minnesota State-Federal Brucellosis Laboratory and were collected over a 1-year period. Results of this study revealed an antibody prevalence of 65.5% to bovine respiratory syncytial virus. The distribution of antibody titers is presented, as well as analysis of titers based on breed, sex, and age of the cattle. PMID- 4014839 TI - Impairment of sympathetic pulmonary vasoconstriction by 3-methylindole in cattle. AB - Sixteen Holstein cattle allotted into 4 groups (4 cattle/group) were each given a single oral dosage of 0.2 g of 3-methylindole (3MI)/kg of body weight. The groups were killed at 12, 24, 48, and 72 hours, respectively, after 3MI administration. Comparison of clinical signs, pathologic pulmonary lesions, and in vitro pulmonary artery responses to pharmacologic stimuli was made between the 4 treated groups and 8 control Holstein cattle of similar age. Clinical signs of pulmonary distress first appeared 8 to 12 hours after 3MI administration. After 20 hours, clinical signs included dyspnea, moderate depression, and a marked expiratory grunt. A partial remission of these clinical signs was seen between 30 and 45 hours after 3MI administration. After remission, the cattle had clinical signs of severe dyspnea and depression and expiratory grunts were more pronounced. Pathologic pulmonary lesions, including heavy rubbery lungs, dilated interlobular septae, and subplural air bullae characteristic of pulmonary edema and interstitial emphysema were observed. The lungs of treated cattle did not collapse when the thorax was incised at necropsy. In vitro pulmonary artery strips contracted dose dependently to norepinephrine (NE). Group I tissues (12 hours after 3MI administration) responded similarly to control samples. Group II tissues (24 hours after 3MI administration) had a significant inhibition (P less than 0.05) in response to NE stimulation as compared with controls. PMID- 4014840 TI - Pathologic changes associated with induced small intestinal strangulation obstruction and nonstrangulating infarction in horses. AB - Arteriovenous (ischemic strangulation obstruction, ISO) or venous (hemorrhagic strangulation obstruction, HSO) occlusions were created in the jejunum of 5 anesthetized horses and were left in situ for 1-, 2-, or 3-hour intervals. Segments were evaluated grossly for color, thickness, and motility. The horses were euthanatized, and the degree of mucosal slough, edema, congestion, and hemorrhage was determined histologically. Segments subjected to ISO became dark, but did not contain edema or hemorrhage. Segments subjected to HSO were characterized by progressive congestion, edema, and hemorrhage especially in the mucosal layer. Histologically, the mucosal epithelium was affected approximately equally by ISO or HSO, although more gross changes were evident in segments subjected to HSO. PMID- 4014841 TI - Comparison of peripheral blood and uterine-derived polymorphonuclear leukocytes from mares resistant and susceptible to chronic endometritis: chemotactic and cell elastimetry analysis. AB - The functional competence of peripheral blood and uterine-derived polymorphonuclear leukocytes (PMN) from 12 mares were analyzed for chemotactic responsiveness using a chemotactic chamber (filter) assay and for deformability by cell elastimetry analysis. Peripheral blood PMN obtained from control mares and from 8 mares experimentally inoculated via the uterus with 1 x 10(9) Streptococcus zooepidemicus had similar normal chemotactic responsiveness and were highly deformable before and at 12 hours after inoculation. Uterine PMN obtained 12 hours after uterine inoculation with S zooepidemicus from resistant mares were not as deformable as peripheral blood PMN, but were within normal functional limits. The chemotactic responsiveness of uterine PMN from these mares was normal. Uterine PMN obtained from mares considered susceptible to endometritis 12 hours after uterine infection did not have chemotactic responsiveness and were nondeformable. The results indicated profound differences in the functional competence of uterine PMN between mares considered resistant and susceptible to chronic endometritis. PMID- 4014842 TI - Plasma and serum concentrations of phenylbutazone and oxyphenbutazone in racing Thoroughbreds 24 hours after treatment with various dosage regimens. AB - The plasma and serum concentrations of phenylbutazone (PBZ) and oxyphenbutazone were measured in 158 Thoroughbred horses after various doses of PBZ wer given. All horses were competing or training at racetracks in various parts of the country. All horses used in the study had not been given PBZ 24 hours before they were placed on a specific dosage schedule. Samples were collected 24 hours after the last PBZ administration. Four grams of PBZ were given daily by stomach tube, paste, or tablet for 3 days. On day 4, 24 hours before sample collection, an IV dose of 2 g of PBZ was given, regardless of the dose and method of administration. The 24-hour PBZ plasma concentrations were 3.51, 6.13, and 6.40 micrograms/ml, respectively. After 2 g of PBZ was administered IV daily for 4 days, the plasma PBZ concentration was 4.16 g/ml; after a single 2-g IV administration, the serum concentration was 0.87 g/ml. Concentrations of oxyphenbutazone were 3.35 (stomach tube), 4.29 (paste), 3.60 (tablet), 3.65 (4 day IV), and 1.11 g/ml (single IV). A significant relationship was not found between the serum and the urinary concentrations at this 24-hour measurement. Split samples sent to various laboratories confirmed the stability of high performance liquid chromatography as a method of analysis. PMID- 4014843 TI - Variation of fiber types in the triceps brachii, longissimus dorsi, gluteus medius, and biceps femoris of horses. AB - The distribution of type-I and type-II fibers in 9 different parts of the musculi triceps brachii, longissimus dorsi, gluteus medius, and biceps femoris was studied to determine whether biopsies from these muscles give reliable information. All 4 investigated muscles were not homogeneous in their fiber-type distribution. Large differences existed among different muscle parts. The percentage of type-I fibers increased toward the deeper and cranial parts of the muscles. In the same zone of the gluteus muscle, differences of 30% were found for type-I fibers. Therefore, results obtained by biopsies of muscles must be interpreted with caution. PMID- 4014844 TI - Simultaneous cecostomy and ileal cannulation with a modified flexible T cannula in gilts. AB - A surgical procedure was developed for the simultaneous cannulation of the ileum and fistulation of the cecum in breeding-age gilts to study the effects of enteric microflora on the nutritional requirements and/or status of the pig. Flexible T-shaped cannulae were made from plastic tubing, placed surgically in the caudal part of the ileum, and exteriorized in the right paralumbar fossa. After the exteriorization of the cecal apex in the right flank area, a cecal fistual was made caudoventral to the ileal cannula. Prececocolonic contents could be collected from the ileal cannulae and/or substances could be infused into the cecum. The flexible cannulae were light weight (35 g), were easily replaced when dislodged with minimal tissue trauma and minimal discomfort to the animal, and had good animal tolerance and patency in long-term experiments. The cecal fistulae allowed the direct introduction of various substances into the cecum. There was little external projection from the abdominal wall, and the fistulae were subject to minimal leakage. The procedure did not adversely affect the subsequent health or performance of the 43 gilts used in the experiment. Postmortem examination of gilts euthanatized 12 to 26 weeks postoperatively revealed normal tissue adhesions around the surgical sites with no detrimental effects on the gastrointestinal tract. PMID- 4014845 TI - Serologic classification of two ovine adenovirus isolates from the central United States. AB - Two ovine adenovirus (OAV) strains (RTS-42 and RTS-151), isolated from lambs in the central United States, were compared using 2-way cross-neutralization tests with the 6 recognized OAV species, 9 bovine adenovirus species, and 4 porcine species. Virus RTS-42 was identified as OAV type 5, confirming previous results. Virus RTS-151 was identified as OAV type 6, although the serologic crossing was largely one-sided. PMID- 4014846 TI - Propionate loading test for liver function during experimental liver necrosis in sheep. AB - The first objective of this work was to study the conversion of propionate to glucose by liver of the sheep during experimentally induced liver necrosis. An additional objective was to determine the most appropriate sampling time after a propionate load has been given to use glucose concentration as an aid in the diagnosis of disturbed liver function. Sodium propionate (3 mmol/kg) was injected IV into 6 healthy sheep before and after they were given carbon tetrachloride (20% CCl4 in mineral oil; 0.25 ml of CCl4/kg, orally). To differentiate the effects of liver necrosis from the effects of decrease in food intake after CCl4 administration, 5 sheep which were fasted for 2 days, but not given CCl4, were studied. Microscopically, liver necrosis was observed, as well as an increase of fatty infiltration in nonnecrotic liver tissue. After sheep were given CCl4, the plasma liver-specific enzyme activities (namely, those of iditol dehydrogenase and gamma-glutamyl-transferase) were elevated. Microscopic and enzymatic changes were not observed in fasted animals. Serum sulfobromophthalein (BSP) half-life (t1/2) was markedly increased in the sheep given CCl4 treatment (t1/2 = 22.8 +/- 11 minutes) when compared with the t1/2 before treatment (t1/2 = 2.5 +/- 0.2 minutes). The BSP t1/2 did not differ between fed and fasted sheep. The t1/2 of the IV propionate load increased significantly, from 6.9 +/- 0.4 minutes in the control sheep to 12.8 +/- 2 minutes in the CCl4-treated sheep, whereas an insignificant increase was seen after fasting (6.8 +/- 1 minutes to 8.3 +/- 1 minutes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4014847 TI - Use of nonprotein nitrogen in pigs: effects of dietary urea on the intestinal microflora. AB - The fecal flora of 2 pigs given an optimal protein diet (digestive crude protein, 13.3%) with 2% urea, 2 pigs given a low protein diet (digestive crude protein, 5.7%) with 2% urea, and 2 pigs given a low protein diet only were bacteriologically investigated before feeding of each diet and on feeding days 21 and 38. The addition of urea to a low protein diet was significantly decreased Lactobacillus (P less than 0.001), Bacteroidaceae (P less than 0.01), Peptococcaceae (P less than 0.05), and Megasphaera (P less than 0.01) in the feces. In addition, there was a marked suppression of anaerobic curved rods (mainly Selenomonas) to undetectable amounts in the feces. A significant reduction (P less than 0.01) of Bifidobacterium and a marked suppression of Megasphaera to undetectable amounts were observed in the feces of pigs given low protein diets without urea. Microbial groups in the ileum and colon of pigs on feeding day 38 were also analyzed. Effects of dietary urea on the intestinal flora included: (i) anaerobic curved rods and spiral rods were restricted mainly to the colon, (ii) smaller numbers of yeasts were present in the intestine, and (iii) Bacteroidaceae, Peptococcaceae, and Eubacterium in the colon were not changed. Many anaerobic isolates, including curved rods and spiral rods, in the colon of pigs may have an important role in urea use. PMID- 4014848 TI - Effects of atropine, acepromazine, meperidine, and xylazine on gastroesophageal sphincter pressure in the dog. AB - Gastroesophageal sphincter (GES) pressure was 47.9 +/- 1.2 mm of Hg in nontreated dogs. Treatment with atropine, acepromazine, and xylazine reduced GES pressure to 13.2 +/- 2.03, 18.6 +/- 2.14, and 11.7 +/- 1.19 mm of Hg, respectively. Treatment with meperidine resulted in phasic contractions with minimum and maximum pressures of 27.9 +/- 4.55 and 98.9 +/- 9.16 mm of Hg, respectively. Drugs used in anesthetic procedures can reduce GES pressure in dogs. PMID- 4014849 TI - Brain stem auditory-evoked response of the nonanesthetized dog. AB - The brain stem auditory evoked-response was measured from a group of 24 healthy dogs under conditions suitable for clinical diagnostic use. The waveforms were identified, and analysis of amplitude ratios, latencies, and interpeak latencies were done. The group was subdivided into subgroups based on tranquilization, nontranquilization, sex, and weight. Differences were not observed among any of these subgroups. All dogs responded to the click stimulus from 30 dB to 90 dB, but only 62.5% of the dogs responded at 5 dB. The total number of peaks averaged 1.6 at 5 dB, increased linearly to 6.5 at 50 dB, and remained at 6.5 to 90 dB. Frequency of recognizability of each wave was tabulated for each stimulus intensity tested; recognizability increased with increased stimulus intensity. Amplitudes of waves increased with increasing stimulus intensity, but were highly variable. The 4th wave had the greatest amplitude at the lower stimulus intensities, and the 1st wave had the greatest amplitude at the higher stimulus intensities. Amplitude ratio of the 1st to 5th wave was greater than 1 at less than or equal to 50 dB stimulus intensity, and was 1 for stimulus intensities greater than 50 dB. Interpeak latencies did not change relative to stimulus intensities. Peak latencies of each wave averaged at 5-dB hearing level for the 1st to 6th waves were 2.03, 2.72, 3.23, 4.14, 4.41, and 6.05 ms, respectively; latencies of these 6 waves at 90 dB were 0.92, 1.79, 2.46, 3.03, 3.47, and 4.86 ms, respectively. Latency decreased between 0.009 to 0.014 ms/dB for the waves. PMID- 4014851 TI - Characteristics of F and H waves of ulnar and tibial nerves in cats: reference values. AB - The latencies and latency rates of H and F waves were determined by percutaneous stimulation of the ulnar and the tibial nerves of healthy cats. In the ulnar and tibial nerves, the latency rates of H wave evoked compound action potentials were 49.1 +/- 7.3 and 44.1 +/- 2.7 m/s, respectively, and of F waves were 68.1 +/- 9.6 and 57.1 +/- 6.2 m/s, respectively. The H wave response of cats was more variable in latency and amplitude than that reported in the dog. PMID- 4014850 TI - Effects of fentanyl citrate and droperidol on electroencephalographic findings in dogs. AB - Electroencephalograms were recorded from 10 dogs before, immediately after, and every 10 minutes (for 60 minutes) after IV injection of 0.005 ml of a fentanyl citrate and droperidol combination/kg of body weight. Narcosis was adequate for recording. At 30 to 40 minutes after injection, tail wagging was the only adverse reaction (EEG artifact) observed. The only changes in EEG activity observed were a slight increase in amplitude of the dominant activity and an increase in spindle-like activity. Daily repetition for 5 days did not alter the EEG pattern or the behavior of the dogs. PMID- 4014852 TI - Clinical, biochemical, acid-base, and electrolyte abnormalities in cats after hypertonic sodium phosphate enema administration. AB - Ten clinically healthy cats were allotted into 2 groups. Group A was given the low (60 ml), and group B was given the high (120 ml) recommended dose of a commercial hypertonic sodium phosphate enema. Enema retention was enforced. All cats developed clinical and/or laboratory abnormalities, with group B cats being more severely affected. Clinical signs that occurred rapidly included depression, ataxia, vomition, bloody diarrhea, mucous membrane pallor, and stupor; tetany was not seen. One cat in group B died. Laboratory abnormalities included hypernatremia, hyperphosphatemia, hypocalcemia, hyperglycemia, calculated hyperosmolality, and metabolic acidosis with high anion gap probably due to hyperlacticacidemia. There were no significant gross or microscopic lesions associated with enema administration. Therefore, the use of hypertonic sodium phosphate enema at recommended doses is potentially dangerous to cats. PMID- 4014853 TI - DSM-III and the politics of truth. PMID- 4014854 TI - Regulation of tissue oxygen extraction is disturbed in adult respiratory distress syndrome. AB - To test the hypothesis that regulation of tissue oxygen (O2) extraction is disturbed in adult respiratory distress syndrome (ARDS), the relationship between O2 availability and O2 extraction ratio (O2ER) was studied in 36 patients with pulmonary edema who met the criteria for either ARDS (n = 21) or acute congestive heart failure (CHF) (n = 15). We found that in response to changes in the levels of O2 availability there was a significantly (p = 0.01) greater negative correlation of change in O2ER for the CHF (r = -0.67) than for the ARDS group (r = -0.41). Whereas patients with CHF eventually died of pump failure and low O2 delivery, the ARDS group developed multiorgan failure, especially renal failure, despite significantly higher ratios of O2 availability to O2 consumption. These findings suggest that patients with ARDS have lost their ability to regulate their tissue O2 extraction to compensate for changes in the availability of O2 in order to meet demand. Pulmonary capillary endothelial injury, through its role on whole-body metabolism, may be responsible for this observation. PMID- 4014855 TI - Nitrogen washout and mortality. AB - We studied the association between different tests of pulmonary function and subsequent mortality. Subjects were drawn from an epidemiology study of chronic obstructive pulmonary disease. Between 1971 and 1976, 2,539 nonpatient adults had tests of forced expiration, diffusing capacity, and single-breath nitrogen washout. By 1981, 115 of those subjects had died, including 3 from known lung disease. In assessing the relationship between lung function and mortality, the following tests of pulmonary function were examined: forced expiratory volume in one second as a percentage of forced vital capacity, forced expiratory volume divided by height cubed, slope of phase III from the single-breath nitrogen test, closing capacity, diffusing capacity for CO, and the ratio of maximal flow at 75% to that at 25% vital capacity. When adjustments for age and smoking were made, slope of phase III was strongly associated with mortality, even more so than tests of forced expiration. There are two possible explanations for this striking relationship between these observed abnormalities of lung function and subsequent overall mortality (which is largely from nonpulmonary disease): the lungs may serve to protect other systems of the body and therefore poor pulmonary function may contribute to a number of diseases leading to death, or lung function may merely reflect existing disorders in other systems of the body, and the observed association between mortality and pulmonary function is a byproduct of nonpulmonary diseases. PMID- 4014856 TI - Effects of spirometry standards in two occupational cohorts. AB - Characteristics of subjects with nonreproducible lung function tests (test failures) are described in two studies of occupational respiratory disease. According to current guidelines for spirometry, subjects with test failure are excluded from analyses of epidemiologic pulmonary function data. Among 415 Chinese cotton textile workers, the prevalence of byssinosis was 5.8% for subjects with repeatable tests and 13.3% for subjects with test failure. In regression analysis, the estimate of the association between cotton dust exposure and FEV1 decreased when subjects with test failure were excluded. In a second cohort of 378 asbestos-exposed machinists, the prevalence of chronic bronchitis was significantly greater among those with test failure. Considering only subjects with repeatable measurements, FEV1 was lower among textile workers with byssinosis and machinists with chronic bronchitis than among their asymptomatic coworkers. This suggests that, on average, subjects with poor test performance had lower (unobserved) FEV1 values, and therefore that the exclusion of subjects with test failure may cause selection bias. PMID- 4014857 TI - Epidemiology of tuberculous infection in a chronic care population. AB - A prospective study of serial tuberculin skin testing was performed on 642 patients from the chronic care wards of a Veterans Administration Hospital. Five hundred eighty-eight patients without a documented history of tuberculosis or a positive tuberculin skin test received an initial 5 TU PPD, and results in 139 were positive (23.6%). Of those initially tuberculin negative, 398 received a second 5 TU PPD 2 to 4 wk later; 45 (11.3%) showed a booster effect. Of the initial 642 patients, 64 had documented negative tuberculin skin tests within the year preceding the survey. Eight (12.5%) of the 64 patients were positive at the initial survey. There were 213 patients with 2 negative tuberculin tests within the first 4 wk of the study who were followed for the year of the study, and 10 converted their tuberculin skin test for a converter rate of 4.7%. The decrease in the converter rate from 12.5 to 4.7% suggests that the initial converter rate was falsely elevated by the booster effect. The high rate of conversion during the year of the study (4.7%) suggests that there may have been inapparent spread of tuberculous infection among patients in this chronic care facility. PMID- 4014858 TI - Size aspects of metered-dose inhaler aerosols. AB - The aerodynamic size distribution of several bronchodilator and corticosteroid metered-dose inhaler (MDI) aerosols was estimated in both dry and humid (90% RH) air environments with a six-stage cascade impactor. The distribution of aerosol size that penetrated into a simulated lung model were also measured. The size distributions were approximately log-normal and ranged from 2.4 to 5.5 micron in mass median aerodynamic diameter (MMAD) with geometric standard deviation (GSD) of 1.7 to 2.5 in a dry environment. In humid air, MMAD increased from 1 to 26% above the dry air state, but GSD remained unchanged. The size of aerosol delivered by MDI that penetrated into a simulated lung model fell to 2.4 to 2.8 micron in MMAD (GSD, 1.9 to 2.2). In contrast to aerosols produced by MDI, MMAD of an aerosol of cromolyn sodium powder dispersed by a Spinhaler increased rapidly with increasing humidity, 5.6 +/- 0.3 micron in dry air and 10.1 +/- 0.8 micron in 90% RH air. Finally, the factors influencing size of MDI-delivered aerosols, including formulation, canister pressure, physicochemical properties of propellants, and design of the valve and actuator orifices are discussed. Effective delivery of MDI-generated aerosols into the lung is highly dependent on particle dynamics and jet flow, and no single parameter can produce a unique particle size and jet pattern. PMID- 4014859 TI - A comparison of the ferruginous body and uncoated fiber content in the lungs of former asbestos workers. AB - Tissue samples from 12 former asbestos workers were digested and analyzed for ferruginous body and uncoated fiber populations. It was noted that there were large numbers of nonasbestos fibers in each of the samples. In some samples, these fibers constituted over 80% of the total uncoated fibers, and they could greatly influence the data as to asbestos content of the tissue unless differentiated by light and electron microscopic techniques, such as X-ray energy dispersive analysis. There were great variations in the numbers of uncoated fibers per ferruginous body between the individual workers. The digested samples from lungs of 2 workers yielded no ferruginous bodies by light microscopy, even though these samples by electron microscopy contained respective loads of 780,000 and 1.2 million uncoated amphibole fibers per gram. Light microscopy examination of adjacent tissues confirmed mild fibrosis in both workers. Ferruginous bodies serve as a general marker for asbestos exposure. However, our data suggest that their absence in tissue with interstitial fibrosis from a worker with previous occupational exposure may not be sufficiently conclusive to rule out asbestos induced disease. Rather, as shown by our data, individual exceptions may require correlated analysis by analytical electron microscopy in order to define particulate load and support the diagnosis of the disease. PMID- 4014860 TI - Abnormal ventilation scans in middle-aged smokers. Comparison with tests of overall lung function. AB - We have assessed the uniformity of regional ventilation during tidal breathing using continuous inhalation of krypton-81m in 43 male, lifelong nonsmokers and 46 male, current cigarette smokers (mean daily consumption 24.1 cigarettes/day) between 44 and 61 yr of age and with mild or no respiratory symptoms. All subjects had normal chest radiographs. The results of the ventilation scans were compared with tests of overall lung function (spirometry, maximal expiratory flow volume curves, and single-breath N2 test). Diffuse abnormalities of the ventilation scan were found in 19 (41%) of the 46 smokers but in none of the nonsmokers. Focal abnormalities were found in 7 smokers and 3 nonsmokers. Smokers showed the expected abnormalities in overall lung function (reduced FEV1 and VC, increased single-breath N2 slope, and closing volume), but in individual smokers there was only a weak relation between the severity of abnormality of overall lung function and an abnormal ventilation scan. Abnormal scans could be found when overall lung function was normal and were not invariably found when significant abnormalities in FEV1/VC or N2 slope were present. There was no relation between the presence of chronic expectoration and an abnormal scan. The prognostic significance of an abnormal ventilation scan in such smokers remains to be established. PMID- 4014862 TI - Tuberculin test. Variability with the Mantoux procedure. PMID- 4014861 TI - Protection against pulmonary oxygen toxicity in rats by the intratracheal administration of liposome-encapsulated superoxide dismutase or catalase. AB - To test the feasibility of using liposomes to deliver therapeutic agents to the lungs, the effect of liposome-encapsulated superoxide dismutase (SOD) or catalase on pulmonary oxygen toxicity was studied in rats. The SOD or catalase was encapsulated in negatively changed multilamellar liposomes and administered directly into the trachea of adult rats, which were subsequently exposed to hyperoxia (greater than 95% O2). Response to hyperoxia was examined by studying lung SOD and catalase activities, survival rates, and lung morphology. Rats receiving liposome-encapsulated SOD or catalase showed increased levels of enzyme activities in the lung homogenates compared with those in the control groups after 24 to 72 h of hyperoxic exposure. Elevated enzyme levels in the lungs of rats treated with liposome-encapsulated SOD or catalase were accompanied by a significant improvement in survival rates after 72 h of hyperoxic exposure and less lung injury than in the other control groups. PMID- 4014863 TI - Tuberculin test. A re-emphasis on clinical judgement. PMID- 4014864 TI - Summary and recommendations of a workshop on the investigative use of fiberoptic bronchoscopy and bronchoalveolar lavage in asthmatics. AB - The participants in the workshop reached unanimous consensus that as an investigative tool, BAL has enormous potential for extending knowledge of the immunopathogenesis of asthma. When utilized according to these guidelines, maximal knowledge may be gained with minimal risks to study subjects. However, we wish to emphasize that the extent to which the safety of the procedure applies to those asthmatics with more symptoms and an FEV1 of less than 60% of predicted remains to be established by carefully controlled clinical investigations. PMID- 4014865 TI - The definition of emphysema. Report of a National Heart, Lung, and Blood Institute, Division of Lung Diseases workshop. PMID- 4014866 TI - Diagnosis of pulmonary amyloidosis by transbronchial biopsy. AB - Previously reported cases of pulmonary parenchymal amyloidosis were diagnosed by open lung biopsy or postmortem examination. We describe 3 patients who were found to have amyloid deposits within the lung parenchyma by flexible fiberoptic bronchoscopy. In each case, the diagnosis was suspected when a waxy eosinophilic substance was observed within the alveolar walls of transbronchial biopsy specimens stained with hematoxylin-eosin. When stained with Congo red and examined under polarized light, this amorphous material exhibited the apple-green birefringence characteristic of amyloid fibrils. We suggest that a diagnosis of pulmonary amyloidosis can be made by transbronchial biopsy provided the appropriate histologic stains are employed. Special stains for amyloid should be obtained whenever histologic sections from transbronchial biopsy specimens reveal amorphous eosinophilic material within the alveolar septa or within the walls of small vessels. PMID- 4014867 TI - Sustained-release theophylline reduces dyspnea in nonreversible obstructive airway disease. PMID- 4014868 TI - Do prostaglandins have a role in breathlessness? AB - The effects of indomethacin on the relationship between breathlessness and minute ventilation during exercise have been determined in a double-blind, randomized study on 6 normal subjects. Indomethacin did not significantly after ventilation or oxygen uptake either at rest or during submaximal exercise. Breathlessness was assessed with visual analogue scales, and, when compared with placebo, the sensation was significantly reduced in relation to ventilation (p less than 0.02). These findings provide evidence of a possible role for prostanoids in the mechanisms that give rise to breathlessness. PMID- 4014869 TI - Prevalence and nature of bronchial hyperresponsiveness in subjects with chronic obstructive pulmonary disease. AB - The prevalence, nature, and severity of bronchial hyperresponsiveness in subjects with chronic obstructive pulmonary disease (COPD) is not known. To determine these factors, a 1 in 4 random sample of adults attending the Busselton population survey was studied. Subjects answered a modified Medical Research Council questionnaire and had spirometric function tested. They were defined as having COPD or asthma from the questionnaire. Bronchial responsiveness to histamine was measured using the rapid method, and results in the subjects with COPD were compared with those in asthmatic subjects with abnormal lung function. Fifty-nine subjects with COPD had a histamine inhalation test, and of these, 27 had bronchial hyperresponsiveness (BHR) (PD20FEV1 less than 3.9 mumol). The position of the dose response curves of the subjects with COPD overlapped considerably with those obtained from the 17 asthmatics. The geometric mean values for PD20FEV1 for these 2 groups were significantly different (p less than 0.001). There was a good correlation between FEV1/FVC and PD20FEV1 values in the subjects with COPD but not in the asthmatic subjects. Pretreatment with 600 micrograms of aerosolized fenoterol significantly improved the PD20FEV1 values in 11 subjects with COPD (1.26 to 6.16 mumol; p less than 0.001). The results suggest that approximately half the subjects with COPD in a general population have BHR but this BHR has different characteristics from that occurring in asthmatic subjects. PMID- 4014870 TI - Ozone response relationships in healthy nonsmokers. AB - Significant concentration responses were observed in FVC, FEV1, FEF25-75, SGaw, IC, and TLC in 20 healthy, nonsmoking volunteers exposed randomly to 0.00, 0.10, 0.15, 0.20, and 0.25 ppm O3. In addition, significant response changes for FVC, FEV1, and FEF25-75 were shown with time over the 2-h exposure. Intermittent, heavy exercise (VE, 68 L/min) lasting 14 min was employed every 30 min during exposure. Inspection of the concentration and time response curves suggests that the threshold for the group response is at or below 0.15 ppm O3. Six subjects experienced decreases greater than 5% in FEV1 or greater than 15% in SGaw at 0.15 ppm. This concentration is only slightly higher than the 1-h O3 National Ambient Air Quality Standard. A dose-related response was also seen for cough, nose and throat irritation, and chest discomfort. The work load, length of exposure, and individual sensitivity must be considered for establishing a safe O3 exposure level. PMID- 4014871 TI - Determinants of maximal inspiratory pressure in chronic obstructive pulmonary disease. AB - Inspiratory muscle strength in COPD could be reduced either because of mechanical disadvantage consequent to increased lung volume or because respiratory muscles share in generalized muscle weakness. To assess the relative contributions of these factors, we measured maximal inspiratory and expiratory pressures (Pimax, Pemax, cmH2O) at RV and TLC, respectively, in 32 patients with COPD. The TLC, RV, and diaphragm length index at RV (DLI, cm/cm height) were determined roentgenographically and compared with values from 22 normal subjects studied at comparable lung volume. Half the patients with COPD had normal and half had low values of Pemax, but both groups had similar values of TLC, RV, and DLI. In patients with COPD, Pimax correlated (p less than 0.001) with Pemax (r = 0.73) and DLI (r = 0.64). The slope of the Pimax-DLI relationship was essentially the same in both groups of patients with COPD as it was in the normal subjects. However, at any value of DLI, Pimax was in the normal range in patients with normal Pemax, but significantly lower in patients with low Pemax (p less than 0.001). Expressing Pimax as a combined function of Pemax and DLI yielded the highest correlation (r = 0.84, p less than 0.001), with Pemax explaining 46% and DLI explaining 35% of the variance in Plmax not explained by the other variable alone (p less than 0.001). The PaCO2 was elevated in 13 of 18 patients whose Pimax was less than 55 cm H2O, and inversely correlated with Pimax (r = -0.66, p less than 0.005).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4014872 TI - Inspiratory muscle function in patients with severe kyphoscoliosis. AB - In 9 patients with severe kyphoscoliosis we studied inspiratory muscle function by measuring transdiaphragmatic pressure (Pdi) and its components: gastric (Pga) and esophageal (Pes) pressures during quiet breathing. Maximal Pdi and maximal inspiratory mouth pressure (Pimax) were also measured. The results showed that Pimax and Pdimax were significantly lower in patients than in normal subjects. During quiet breathing, all patients had positive swings in Pga, indicating an active contraction of the diaphragm, but Pes was significantly more negative, suggesting the recruitment of intercostal and accessory inspiratory muscles. We did not find significant correlations between Pimax, Pdimax, delta Pga/delta Pes, FVC, PaO2, or PaCO2 and the degree of spinal deformity. The FVC tended to correlate with Pimax (r = 0.63) and with Pdimax (r = 0.53). The Pdi correlated with PaO2 (r = 0.66) and with PaCO2 (r = -0.76; p less than 0.05). A significant correlation was also observed between Pimax and PaO2 (r = 0.785; p less than 0.05) and between Pimax and PaCO2 (r = -0.86; p less than 0.01). We conclude that impairment of inspiratory muscle function is related to the development of ventilatory failure in kyphoscoliosis. PMID- 4014873 TI - Relationship between respiratory muscle electromyogram and rib cage motion in tetraplegia. AB - In an attempt to understand the intersubject variation in rib cage motion in tetraplegia, and to assess the isolated action of the diaphragm on the human rib cage, we studied the pattern of rib cage motion in relation to the pattern of nondiaphragmatic respiratory muscle electromyogram (EMG) in 20 tetraplegic patients breathing at rest in the seated posture. The general pattern included a greater expansion of the lower than of the upper rib cage, and a greater and earlier expansion of the lower rib cage in its transverse than in its anteroposterior (AP) diameter. However, whereas the upper rib cage moved paradoxically inward with inspiration in 11 patients, it did not move or slightly expanded in 9 patients; in 1 of these, all rib cage diameters increased in the same proportion during inspiration as during relaxation. This intersubject variation was not related to the duration of tetraplegia, the pattern of the abdominal muscle EMG, or the presence of continuous spastic EMG activity in the parasternal intercostals. By contrast, it was related in part to the pattern of scalene EMG activity: upper rib cage AP paradox was present in 7 of 8 patients with spastic or silent scalenes but only in 4 of 12 patients with phasic inspiratory scalene EMG activity. When studied during quiet breathing in the supine posture, the 8 subjects with denervated scalene, intercostal, and abdominal muscles still showed inspiratory increase in the rib cage transverse diameter, but in 7 patients the lower rib cage AP diameter decreased in concert with the upper rib cage AP diameter.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4014874 TI - Usefulness of tumor markers in serum and bronchoalveolar lavage of patients undergoing fiberoptic bronchoscopy. AB - To evaluate the diagnostic usefulness of simultaneous determinations of 4 tumor markers (carcinoembryonic antigen, calcitonin, creatinine kinase-BB, and DNA), we studied 31 patients with lung cancer, 22 with benign lung disease, and 15 normal volunteers as control subjects. The measurements were made by radioimmunoassay in bronchoalveolar lavage (BAL) and in serum obtained on the same day. The results showed that in serum, only CEA levels were significantly higher in malignancy; in lavage fluids, all 4 markers were abnormally high in cancer patients when compared with control subjects (p less than 0.05); there was no correlation between the levels in lavage and those in the bloodstream. When the mean levels in lavage of the normal control subjects were designated as the limits for a positive test, significant association was found between malignancy and abnormally elevated marker concentration (p less than 0.01). The particular combination of CEA-BAL greater than 35 ng/mg, CEA-serum greater than 4 ng/ml, and calcitonin-BAL greater than 120 pg/mg taken together with the results of bronchoscopy (histologic and cytologic) showed the highest discriminating power between malignant and benign lung disease. The sensitivity of the bronchoscopy procedure increased from 50 to 89%, with at least 2 positive markers, and had a specificity of 71%. When both bronchoscopy and all 3 markers were negative, the results showed a negative predictive value of 100%. We conclude that tumor marker levels in lavage are a useful aid in the diagnosis of malignancy in patients undergoing bronchoscopy. PMID- 4014875 TI - The effect of acute airway inflammation on bronchial reactivity in guinea pigs. AB - This study compared airways reactivity before and after an inflammatory response was induced in the airways by exposing them to cigarette smoke. Airways reactivity was measured to graded doses of histamine using a standard technique in 24 animals without drug pretreatment, in 17 pretreated with propranolol, in 17 pretreated with atropine, and in 18 pretreated with both atropine and propranolol. In each group, at least 5 animals not exposed to cigarette smoke served as controls, and the remaining animals were studied in groups of 4 or more at 30 min, 6, and 24 h after exposure to 100 puffs of whole cigarette smoke. The data show that airways reactivity was increased at 30 min but not at 6 and 24 h after exposure to cigarette smoke. Pretreatment with propranolol or the combination of propranolol and atropine prior to the histamine dose-response curve did not affect the increased response seen after cigarette smoke exposure, but pretreatment with atropine abolished it. Comparing this study with our previous histologic studies of the airways in similarly exposed animals, we conclude that the observed increase in airways reactivity occurs during the fluid exudative phase of the inflammatory response before the polymorphonuclear leukocytes migrate into the epithelium. PMID- 4014876 TI - IgA-mediated phagocytosis by mouse alveolar macrophages. AB - Ingestion of antibody-opsonized sheep red blood cells by murine alveolar and peritoneal exudate macrophages was studied. Alveolar macrophages or peritoneal macrophages were isolated by lavage and incubated with TNP-SRBC, which had been preincubated with anti-DNP IgG, IgA, and IgE. Significant enhancement of phagocytosis by alveolar macrophages of TNP-SRBC was mediated by all classes of antibody examined, most markedly with IgG and less so with IgA and IgE. Enhancement of phagocytosis by peritoneal macrophages was mediated by IgG and IgE, but not by IgA. These results suggest that the interaction of IgA and Fc receptors for IgA on alveolar macrophages may increase the level of this cell's function in the mammalian lung to clear pathogens and immune complexes from the alveolar spaces. PMID- 4014877 TI - Breathing and oxygenation during sleep are similar in normal men and normal women. AB - Most patients with the sleep apnea syndrome are male, and it has been suggested that there is a fundamental sex difference in breathing during sleep. To explore this we measured overnight ear oxygen saturation (SaO2), breathing patterns, and electroencephalographic sleep stage in 21 healthy nonobese women (10 premenopausal, 11 postmenopausal) and in 19 healthy nonobese men of similar age. Sleep duration averaged 6 h 51 min (range 343 to 468 min). The 21 older (greater than 45 yr) subjects had more episodes of apnea and hypopnea (p less than 0.01) and became more hypoxemic (p less than 0.02) than did the 20 younger subjects, but there was no sex difference, either in the younger or older subjects, in irregular breathing or nocturnal hypoxemia. Seven subjects 51 to 68 yr of age (4 men and 3 women) had more than 30 episodes of apnea and/or hypopnea and/or SaO2 decreases below 90%, but the clinical importance of this finding is unclear, 6 of the 7 being alive and 5 asymptomatic at an average of 47 months (range 5 to 67) later. Thus, irregular breathing and hypoxemia during sleep are common in both sexes older than 50 yr of age. Previous reports of a sex difference are probably explained by poor matching of the men and women, particularly with regard to body weight. PMID- 4014878 TI - An aggressive treatment approach for adult osteomyelitis. AB - Osteomyelitis in the adult patient has been associated with failure of eradication, late recurrence, nonunion, and prolonged hospitalization. A staged aggressive approach has been used for the past seven years to treat 53 patients with adult osteomyelitis. This approach includes: evaluation of bone necrosis and identification of the etiologic organisms by deep bone culture; radical surgical debridement of devascularized tissue; intensive systemic antibiotics; and early bone and soft tissue reconstruction. All patients have been followed at least 1 year (mean, 33 months). Lower extremity bones predominated in the series (24 tibias, 13 femurs); and 19 patients had bony instability. Thirty-seven patients had initial successful eradication of their infections with 26 of these returning to full activity status. The remaining 16 patients developed recurrent infection; however, 11 patients totally responded to further aggressive treatment. Of the five failures in the total series, three patients required amputation and two patients have persistent infection. Fifteen of the 19 patients with bony instability healed with initial treatment, and the remaining four patients healed with subsequent treatment. Six patients had primary muscle flap soft tissue reconstruction, and an additional two patients had reconstruction as a secondary procedure. In all these patients with tibial instability, bony union was accelerated compared to those patients with tibial instability not receiving muscle flaps (4 months vs 12 months). The muscle coverage provided by either pedicled flaps or transferred by microvascular anastomoses.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4014879 TI - A nonoperative approach to the adult ruptured spleen sustained from blunt trauma. AB - From 1978 to 1983, 53 consecutive adult patients with ruptured spleens documented by radionuclide studies, computerized axial tomography, or surgery, were evaluated at William Beaumont Hospital. Thirty-four patients (64%) underwent an exploratory laparotomy; 33 resulted in a splenectomy and one patient had an attempted splenorraphy which failed. Nineteen patients (36%) were hemodynamically stable on admission, or had transient episodes of hypotension readily reversed by intravenous fluids. They were placed at strict bedrest under intensive monitoring. Two patients deteriorated clinically and were taken to surgery, resulting in a splenectomy on the fourth and sixth hospital day, respectively. Seventeen patients (32%) were successfully treated nonoperatively, representing an 89 per cent success rate. The average admitting hemoglobin in the nonoperative group was 13.2 gm/dl, with an average drop of 1.6 gm/dl, and an average total blood transfusion of 1.2 units. These patients were followed for an average of 19.2 months, with no sequelae from their splenic injury. In a hemodynamically stable adult patient with a splenic injury sustained from blunt trauma, a nonoperative approach is a viable alternative when close intensive monitoring is available. PMID- 4014880 TI - Parathyroid carcinoma. A report of five cases. AB - Parathyroid carcinoma, although rare, represents 0.5-4.0 per cent of the cases of hyperparathyroidism. The authors have encountered five cases of parathyroid carcinoma in their experience treating 445 patients with primary hyperparathyroidism (1.1%) since 1965. All five patients were women, ranging in age fro 29 to 60 years, and had marked hypercalcemia at the time of presentation, with values up to 26 mg/dl in one case. All the tumors were locally adherent to surrounding structures at the time of parathyroidectomy. Pathologically they were characteristic with a dense sclerotic reaction and fibrous bands criss-crossing islands of parathyroid cells. Three patients with local as well as distant metastases have died as a result of recurrent parathyroid carcinoma (follow-up: 2, 3, and 6 years). The remaining two patients became normocalcemic following resection, and have been asymptomatic for 1 and 7 years, respectively. The overall survival and clinical course, in our limited experience with five parathyroid carcinoma cases demonstrates that the morbidity and mortality in these patients is mainly due to local recurrence with the resultant metabolic disturbances, as has been previously noted in the literature. PMID- 4014881 TI - The asymptomatic carotid bruit. AB - Management of the asymptomatic carotid bruit remains a controversial subject. The purpose of this study is to determine whether or not such bruits are important risk factors in the evolution of stroke. Since April 1977, 87 patients with 131 asymptomatic carotid bruits were evaluated with the Gee oculoplethysmography (OPG). Eleven bruits (8.4%) were hemodynamically significant (ophthalmic artery/brachial artery systolic pressure index below 0.69 or a difference of 5 mm Hg or more between the eyes). The patients were reevaluated at 6-month intervals. The mean follow-up was 34 months (range, 1-60 months). During this period, 14 bruits (11.6%) that initially were nonhemodynamically significant (NHS) later became hemodynamically significant (HS). Patients with asymptomatic carotid bruits had a stroke incidence of 10.3 per cent. Patients with HS bruits had a stroke incidence of 24 per cent and a transient ischemic attack (TIA) incidence of 16 per cent, which were significantly higher (P greater than 0.01) compared to the patients with NHS bruits (4.8% incidence of stroke and 3.2% incidence of TIA). Nine patients (10.3%) developed strokes without antecedent TIA and six patients (6.9%) developed TIA. The strokes occurred in the cerebral hemisphere supplied by the carotid artery with HS bruit in three of six patients. The strokes in three patients with NHS bruits were on the same side of the bruits. The TIAs developed in four patients with HS bruits and in two patients with NHS bruits. The authors conclude that the patient with an asymptomatic HS carotid bruit has a high risk of developing a stroke and that surgical treatment is warranted. PMID- 4014882 TI - Differential endothelial injury caused by vascular clamps and vessel loops. I. Normal vessels. AB - Silicone rubber looped tourniquets were compared with standard crossmembered metallic peripheral vascular occlusive clamps in a canine aorto-iliac vessel model to compare the degree and severity of endothelial injury as demonstrated by scanning electron microscopy. The moderate-to-severe injury incurred by the standard clamps was not seen whatsoever with the looped tourniquets. Selective and preferential use of silastic rubber vessel tourniquet loops for vascular occlusion and control is thus advocated. PMID- 4014883 TI - Differential endothelial injury caused by vascular clamps and vessel loops. II. Atherosclerotic vessels. AB - Performance of a vascular anastomosis or repair requires meticulous, gentle technique and a bloodless operative field. Many vascular surgeons rely on commercial "atraumatic" vascular clamps for the latter; however, most experimental evidence incriminates clamps as agents of moderate to severe endothelial and medial injury. Our previous studies in normal canine aortoiliac vessels have demonstrated that silastic rubber vessel loops did not cause injury in that setting; this study examines in vivo atherosclerotic human femoropopliteal artery segments. Ten centimeter segments of perfused femoropopliteal arteries were exposed during performance of above-knee lower extremity amputation for endstage vascular insufficiency. DeBakey, Cooley, Fogarty, and bulldog vascular clamps, and double-looped silastic rubber vessel loops were applied at 3-centimeter intervals for 15 minutes. Each segment was then examined under scanning electron microscopy. All vascular clamps caused endothelial and presumed medial injury; no injury was seen with the vessel loops. Selective and preferential use of silastic rubber vessel loops is thus advocated to minimize iatrogenic complications. PMID- 4014884 TI - Operative risks in patients with colorectal cancer. AB - This study emphasizes the risks in the operative treatment of patients with colorectal cancer. In dissecting our overall operative mortality of 7.4 per cent in consecutive patients over a 5-year period, three factors influencing the outcome were identified. These were the age of the patient, the stage of the disease, and the availability of preoperative bowel preparation by mechanical cleansing and antibiotic suppression of the colonic bacterial flora. Earlier diagnosis and elective resection of prepared bowel offers marked improvement in the operative risk for patients with colorectal cancer. PMID- 4014885 TI - Surgeon's role in ethical decisions. AB - Three clinical cases are summarized to provide examples of reasonably common dilemmas in decision making. Instead of a focus on the solutions, the issue of "who decides" is raised. Contrary to frequent practice, the position is taken that, legally and ethically, substantive patient involvement is required. Factors implicated in physician dominance are briefly discussed, including subjectivity, medical care environments, and notions of the proper role of the physician. Suggestions for the surgeon's role include professional competence, patient education (including effective communication), and separation of the medical/technical aspects of decisions from the ethical/personal ones. PMID- 4014886 TI - Endometriosis in the male. AB - An 83-year-old man with an endometrioma of the lower abdominal wall has been reported. This occurred following the administration of 25 mg of TACE for a period of about 10 years for what was thought to be carcinoma of the prostate. A second transurethral resection done by Dr. R. C. Thompson proved to be adenocarcinoma. Subsequent to this he was continued on TACE. A review of the more commonly accepted theories of the development of endometriosis in the female has been presented. It is pointed out that the separation between the male and female urogenital systems occurs in the embryo between the eighth week and the fourth month. There is always a possibility for remnants of the opposite sex to remain in individuals. No such was seen in the case which is herein reported. Normal phenotype male was demonstrated in the chromosomal evaluation. A review of the literature on endometriosis in the male reveals several cases which have occurred; the origin of which is though to be from the prostatic utricle which is a remnant of the uterus existing in the male. After a prolonged course the patient reported was followed until he died in 1979. There was no recurrence of the abdominal wall mass but persistent low grade carcinoma of the prostate remained. The terminal process was related to cardiovascular disease and not carcinoma of the prostate. There was delay in publication of this unusual case. The original plan was to await final confirmation of the exact pathologic nature of this condition; unfortunately this was never done since a postmortem examination was not performed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4014887 TI - [Detection of subclinical glomerulopathies in childhood]. PMID- 4014888 TI - [Boutonneuse fever in children]. AB - Due to an increase in the number of cases of spotted fever, a prospective study was undertaken in 31 children affected by the disease, including clinical, laboratory and microbiological data from may to october of 1983. The most frequent symptoms found were: fever 100%, "tache noire" 87%, and a maculopapular rash 81%. The Weil-Felix reaction was positive in 65% of them and indirect immunofluorescence was positive in 81%, confirming the sensitivity and specificity of this serologic procedure. The 27 children who received specific treatment, 26 with tetracycline and one with chloramphenicol, differed considerably in a lesser duration of their symptoms, in comparison with the group of children without treatment. PMID- 4014890 TI - [Current trends in breastfeeding in Valladolid]. AB - Authors studied influence of several factors on the election of infant feeding type, and breast feeding incidence and its duration. Two hundred questionnaires were obtained from mothers living within Valladolid. 76% intended to breast-feed. Breast-feeding was not modified by mothers' age, geographic area, instruction, economic-social class, tradition, desired pregnancy, maternal opinion about lactation, aesthetic impairment, maternal or neonatal pathology, husband advice and medical opinion. Nevertheless, frequency of bottle feeding was significantly increased by medical advice contrary to breast-feeding, absence of husband's opinion, hospital admission of the newborn and absence of feeding type distinction by mother. Duration of breast-feeding was longer in low level cultural classes, without differences of mother's age or economic condition. Motives for election were: breast-feed was considered more nutritive (78%), family tradition (10%), and medical advice (8%). Reasons for suspension were: Hypogalactia (70%), medical advice (16%), maternal disease (7%), child disease (3%) and maternal work (3%). PMID- 4014889 TI - [Use of skull radiography in craniocerebral injuries in childhood]. AB - Authors review the usefulness of radiographic skull examination in childhood head injury. Two hundred and forty-two patients assisted at the emergency area were prospectively recorded during one year. Data of filiation and epidemiology and symptoms and signs posed by Leonidas as "high risk criteria" to have a skull fracture, were registered. AP and L X-Ray skull were performed in all patients. Thirteen (5.37%) of them had a fracture. Blood discharge from the ear and skull depressed fracture were more frequently found in the fracture group with statistically significant difference (p less than 0.05 and p less than 0.01, respectively). The probability of positive finding was 8.8 for blood discharge from the ear, 17.6 for skull depressed fracture and 4.4 for bilateral black eyes. Because of no correlation between clinical and radiological findings, the radiographic skull examination must be systematically performed in every head injury if the purpose is to diagnose a fracture. PMID- 4014891 TI - [Arterial pressure in adolescents]. AB - We have studied 932 high school and professional institute students aged fifteen to eighteen in Madrid, of which 406 were males and 526 females. Blood pressure measurements were taken on all the individuals on three separate occasions. The recorded values are expressed in percentiles for age and sex. We have found lower diastolic blood pressure levels than those reported so far in the literature, in agreement with the values recorded by us in children between two and fourteen years old. The prevalence of hypertension in the population studied was 3%, higher in males than in females (4.67% and 1.61%, respectively). We assume the idea that the measurement of blood pressure in teenagers is mandatory because of the high prevalence of arterial hypertension in this age group. PMID- 4014892 TI - [Pharmacokinetics of a new slow-release theophylline preparation in asthmatic children]. AB - This study compares the pharmacokinetics of two preparations of slow-release theophylline, one of them already known, and the other one a new product (micronized), very well accepted by pediatric patients. Two similar groups of fifteen patients each all of then asthmatic children under ten years of age, were selected and given a single oral dose of 10 mg/kg of one of the preparations. The pharmacokinetic parameters (T 1/2, Kel, VD, Cl and AUC) did not differ between both groups. The new product could further be used more safely, due to its lower incidence of "erratic" behaviour. PMID- 4014893 TI - [Surgical correction of subcoronal hypospadias]. AB - In 80% of hypospadias admitted in our out-patients clinic, the meatus was located at the ventral surface of glands, the balano-penile groove or the third of the shaft. In these cases we are performing an operative procedure (Duchekt, 1981) that may be accomplished with minimal complication, a short hospital stay and improve cosmetic appearance. This plastic surgical procedure incorporates a Meatal Advancement and Glandulo-Plasty (MAGPI). We have done 95 of these procedures with an hospital stay average of two days. We have not had any complications. Because of the low complication rate, the short hospitalization required and the benign postoperative course of these children, they believe it is perfectly justifiable to offer this procedure in the correction of subcoronal hypospadias. PMID- 4014894 TI - [Growth retardation, GH deficiency, hyperprolactinemia and delayed puberty]. AB - A case of a male eleven years and three months old, brought to medical attention for short height, is reported. A deficiency of growth hormone associated with hyperprolactinemia without previous clinical manifestations is appreciated in endocrinological study. Detectable tumor is not apparent in any of the investigations performed. HGH and bromocriptine therapy is initiated, resulting in and increase in height and a decrease of prolactin. Currently, at fifteen years four months of age, clinical and analytical data suggest a case of hypogonadism and puberal retardation as well. PMID- 4014896 TI - [Kawasaki disease]. PMID- 4014895 TI - [Ureteral triplication]. PMID- 4014897 TI - [Nomogram for phenobarbital dosage in children]. PMID- 4014898 TI - [The tuberculin test. Clarifications]. PMID- 4014899 TI - Postoperative reflux gastritis: pathophysiology and long-term outcome after Roux en-Y diversion. AB - Sixteen patients with clinical features of postoperative gastritis who had been advised to have a Roux-en-Y diversion were studied prospectively. Studies were done pre- and postoperatively (mean follow-up, 4.9 years; range, 3.8 to 6.9), and the findings were compared with those in 11 control subjects with previous enterogastric anastomosis but with no symptoms. The patients had higher concentrations of bile acids and trypsin in gastric samples than did controls. Patients had greater endoscopic changes, although mucosal histologic characteristics were similar in both groups. Administration of aluminum hydroxide or cholestyramine reduced the aqueous concentrations of bile acids in gastric contents. Roux-en-Y diversion virtually eliminated duodenogastric reflux, and gastroscopic appearances returned to normal. However, Roux-en-Y diversion did not change mucosal histologic characteristics. Symptom scores were reduced in the early postoperative period, but bilious vomiting was the only symptom alleviated consistently and permanently. As a treatment for postoperative gastritis, Roux-en Y diversion offers potential but limited benefits. PMID- 4014900 TI - Undiagnosed sleep apnea in patients with essential hypertension. AB - The prevalence of sleep apnea was studied in 46 middle- and older-aged men with "essential hypertension." Thirty-four age- and weight-similar normotensive men were also studied. Fourteen hypertensive men and three controls had sleep apnea syndrome, as defined as greater than ten apneas per hour of sleep. Hypertensive men with apnea tended to be more overweight and slightly older than the hypertensive men without apnea, but differences were not statistically significant. Individual men with apnea could not be distinguished by their answers on a questionnaire that elicited symptoms related to apnea. Seven hypertensive men with apnea were treated with protriptyline and one with uvulopalatopharyngoplasty, and apnea index (apneas per hour) decreased by 77% from pretreatment levels while mean blood pressure decreased from 149/95 mm Hg to 139/90 mm Hg. Undiagnosed sleep apnea syndrome may be associated with systemic hypertension in many middle- and older-aged men. In some, sleep apnea syndrome could be the cause of hypertension, and in others it may contribute to hypertension of another cause. PMID- 4014901 TI - Risk of acute nonlymphocytic leukemia and preleukemia in patients treated with cyclophosphamide for non-Hodgkin's lymphomas. Comparison with results obtained in patients treated for Hodgkin's disease and ovarian carcinoma with other alkylating agents. AB - Of 602 patients treated for non-Hodgkin's lymphomas, 9 developed overt acute nonlymphocytic leukemia or preleukemia with refractory cytopenia and cytogenetic abnormalities of the bone marrow. A Kaplan-Meier estimate of the cumulative probability of leukemic complications was 6.3 +/- 2.6% (mean +/- SE) 7 years after start of treatment. All 9 patients with leukemic complications belong to a major subgroup of 498 patients treated with alkylating agents, predominantly cyclophosphamide. The risk of leukemic complications in this subgroup was compared with the risk in 312 patients treated with other alkylating agents for Hodgkin's disease, and with the risk in 553 patients treated with dihydroxybusulfan for ovarian carcinoma. Cumulative 9-year risks were 8.0 +/- 3.3%, 12.8 +/- 3.5%, and 7.1 +/- 1.9%, respectively. The general risk of secondary leukemia after long-term treatment with alkylating agents ranges from 1% to 1.5% per year from 2 to at least 9 years after start of treatment. PMID- 4014902 TI - Waterborne Legionella bozemanii and nosocomial pneumonia in immunosuppressed patients. AB - From October 1983 to February 1984, five episodes of nosocomial pneumonia caused by Legionella bozemanii occurred in immunosuppressed patients at a 300-bed community hospital. Pulmonary infiltrates were predominantly patchy and present in multiple lobes and bilaterally; cavitation occurred in one patient. Patients responded promptly and completely to treatment with erythromycin and rifampin. Epidemiologic studies showed that all patients had been continuously or recently hospitalized at the same institution. Legionella bozemanii was cultured from four of the five infected patients, from tapwater in patient care areas, from the hospital's hotwater holding tank, and from soil in an area of excavation and new construction on hospital property. Chlorination and heat sterilization of the tank eliminated L. bozemanii from the water and no further cases were seen. This outbreak reaffirms that excavation and construction are risk factors for the outbreak of nosocomial legionella pneumonia and is the first description of nosocomial infection due to L. bozemanii. PMID- 4014903 TI - Zollinger-Ellison syndrome associated with persistently normal fasting serum gastrin concentrations. AB - A 63-year-old man with a 2-year history of upper gastrointestinal ulcers was found to have the Zollinger-Ellison syndrome. Despite histologic verification of gastrinoma, several fasting serum gastrin concentrations were normal. However, in response to intravenous secretin infusion, a paradoxical increase in serum gastrin levels indicative of gastrinoma was seen. Although serum gastrin concentrations in patients with suspected gastrinoma may be persistently normal, provocative testing may be necessary to establish the diagnosis of the Zollinger Ellison syndrome. PMID- 4014904 TI - The prophylactic treatment of hemophilia B Leyden with anabolic steroids. PMID- 4014905 TI - No hepatitis after treatment with a modified factor IX concentrate in previously untreated hemophiliacs. PMID- 4014906 TI - Conducting clinical research in geriatric populations. AB - Clinical research on geriatric populations requires adaptation of traditional methodologies, modification of expectations, and the development of new procedures. Some aspects of research methodology are unique to studies of geriatric populations. Experience in this relatively new area of geriatric research indicates that new partnerships between researchers and long-term care providers are needed. These new relationships require an understanding of the needs of geriatric populations and of the differences between providers of long term care and of acute-care. Researchers must consider heterogeneity of the population, the probability of multiple diagnoses and treatments, subject attrition, and the possibility of invalid data. Such considerations require extra staff, more time, and increased funding as well as new thinking about study design and protocol implementation. PMID- 4014907 TI - Does central nervous system adaptation to antecedent glycemia occur in patients with insulin-dependent diabetes mellitus? PMID- 4014908 TI - The GPEP Report: II. Clinical education. PMID- 4014909 TI - Connective tissue in the lung: lessons from the Marfan syndrome. PMID- 4014910 TI - Biofeedback for gastrointestinal disorders. Health and Public Policy Committee, American College of Physicians. PMID- 4014911 TI - Streptokinase and the Guillain-Barre syndrome. PMID- 4014912 TI - Cyclosporine and prostaglandins. PMID- 4014913 TI - Thiazides and thiazide-like diuretics in hypertension. PMID- 4014915 TI - Familial benign hypercalcemia. PMID- 4014914 TI - Obesity and erythrocyte sedimentation rates. PMID- 4014916 TI - Primary sclerosing cholangitis in ulcerative colitis. PMID- 4014917 TI - Afebrile diarrhea and Blastocystis hominis. PMID- 4014918 TI - Eosinophilic cerebrospinal fluid pleocytosis and cryptococcal meningitis. PMID- 4014919 TI - Hepatitis B virus markers in Asian families. PMID- 4014920 TI - Heated sera and laboratory tests. PMID- 4014922 TI - [The speech of hebephrenic patients (maladjustment between assimilation and accommodation)]. AB - Previous studies indicate that schizophrenic thought processes show a disturbance in the balance between assimilation and accommodation, as Piaget uses these terms. The authors postulated that this phenomenon could also account for the typical language disorders of hebephrenics, particularly semantic slippage. Every fourth word was deleted from linguistic material produced by eight controls and thirteen hebephrenics (Silverman). Three judges were then asked to fill in the blanks. The deleted words used by the subjects were compared with the replacement words chosen by the judges. The comparison revealed such disorders in hebephrenic speech as semantic alteration (metaphorical and metonymic) of the linguistic tropic type and syntax disorders including inhibition of the expansion of phrases introduced by functional monemes (morphemes), whether primary or secondary. These observations confirm those of other authors, more especially those of Roch Lecours et al. On the basis of Martinet's functional linguistics, Chomsky's generative grammar and Piaget's cognitive psychology, the authors conclude that the psychopathology underlying hebephrenic speech is a disturbance of language rather than of parole and that hebephrenic syntactical distortions are linked to the disturbance in the balance between assimilation and accommodation characteristic of schizophrenic thought processes. PMID- 4014921 TI - Hypothermia and sepsis. PMID- 4014923 TI - [Computer-assisted qualitative study of states of excitement]. PMID- 4014924 TI - [Full-time hospitalization in adult psychiatry: indications and contraindications]. PMID- 4014925 TI - Retinal detachment surgery with the OPMI-6 surgical microscope. AB - Various aspects of retinal detachment surgery using the OPMI-6 surgical microscope as a visual aid are discussed. The following point is made: Provided that subretinal fluid has been drained prior to retinal detachment surgery, holes or tears in the retina will be clearly visible through the OPMI-6, eliminating the need for a posterior mirror lens as a supplemental visual aid. PMID- 4014926 TI - Diffuse unilateral subacute neuroretinitis. AB - In December 1980, a 26-year-old black man came to the Washington Hospital Center Eye Clinic with a unilateral decrease in visual acuity, vitreous inflammation, optic disk pallor, and a degenerated retinal pigment epithelium. A motile subretinal worm was subsequently found. Unlike an earlier series of 18 patients with diffuse unilateral subacute neuroretinitis reported by other authors, this patient exhibited eosinophilia and a highly positive ELISA for Toxocara. PMID- 4014927 TI - Afferent pupillary defect and dilated episcleral and conjunctival vessels in a patient with arteriovenous malformation of the brain. AB - A 42-year-old man had unilateral Marcus Gunn pupil and bilaterally dilated episcleral vessels. After several weeks of testing, using computed tomographic (CT) scanning and angiography, the diagnosis of arteriovenous malformation (AVM) of the brain was made. Except for the partial optic atrophy in the left eye, fundi were normal, with few of the neurologic and systemic manifestations reported previously. To my knowledge, this is the first documented case of an AVM of the brain with no evidence of an arteriovenous shunt, but with an afferent pupillary defect instead. PMID- 4014928 TI - Successfully treated spheno-orbital mucormycosis in an otherwise healthy adult. AB - Orbital mucormycosis usually occurs in patients with demonstrable systemic illness and continues to carry a significant morbidity. We report a case of successfully treated spheno-orbital mucormycosis in an otherwise healthy adult. PMID- 4014929 TI - Cystic conjunctival masses as the presenting sign of disseminated lymphoma. AB - Systemic malignant lymphoma rarely presents as conjunctival masses. Biopsy of unusual cystic conjunctival masses from a 49-year-old woman showed malignant lymphoma. On subsequent examination, the patient was found to have disseminated systemic malignant lymphoma. Examination of possible predictive clinical features of the conjunctival lesions showed that these were of little value in diagnosing the systemic malignancy. PMID- 4014930 TI - Central retinal artery occlusion following transfemoral cerebral angiography. AB - Whereas most ocular complications following cerebral angiography are benign and transient, central retinal artery occlusion following cerebral angiography produces severe permanent visual deficits in nearly 40% of patients. Physicians ordering and performing cerebral angiography should be aware of this complication, since immediate attention to patients with visual disturbance from central retinal artery occlusion may save useful vision. All previously reported cases of central retinal artery occlusion following cerebral angiography have occurred after direct percutaneous carotid angiography. We report a case of central retinal artery occlusion following transfemoral cerebral angiography using a #5 French catheter and meglumine iothalamate (Conray-60) contrast. PMID- 4014931 TI - Congenital retinal arteriovenous communication associated with an ipsilateral cranial dermatofibrosarcoma. PMID- 4014932 TI - Eye irritations induced by smog. PMID- 4014933 TI - Childhood orbital pseudotumor. AB - Pseudotumor of the orbit is an uncommon entity in children. Three patients under 20 years of age with biopsy-proved orbital pseudotumor are presented. A three month-old infant, to our knowledge the youngest patient reported with orbital pseudotumor, had a history similar to those of previously reported cases, whereas the two older patients differed from previously reported cases of childhood pseudotumor in that they lacked constitutional symptoms and orbital pain. Two of the patients were successfully treated with systemic steroids. In one patient, radiation therapy was required to reduce the mass. PMID- 4014934 TI - The incidence of idiopathic preretinal macular gliosis. AB - A series of 1,000 consecutive routine eye examinations performed on patients over the age of 50 was evaluated with particular reference to the presence of idiopathic preretinal macular gliosis (IPMG). In this group, there were 64 patients with IPMG (6.4%), 13 (20%) of whom had bilateral IPMG. The large majority of cases (63%), however, had only minor visual disability as a result of this disorder. PMID- 4014935 TI - [Velopharyngeal rehabilitation after transmaxillary buccopharyngectomy extending to the soft palate]. AB - Two types of velopharyngeal rehabilitation are proposed after transmaxillary buccopharyngectomy extending to the soft palate region. The first method is by velopharyngoplasty, when exeresis has not involved a half or a quarter of the soft palate and at least half of the posterior pharyngeal wall. The second procedure is for use after exeresis involving all or almost all of the soft palate and a half of the posterior pharyngeal wall, and makes use of velum palatinum reconstruction. The method of choice is velopharyngoplasty, excellent functional results being obtained for both phonation and feeding. PMID- 4014936 TI - [Mediastinal tracheotomy in cervicofacial oncologic surgery. Contribution of the pectoralis major myocutaneous flap]. AB - Four cases of anterior mediastinal tracheostomy with myocutaneous Pectoralis Major flap are described. Resection of the manubrium, clavicular heads and the cartilages of the first and second ribs is necessary. The use of myocutaneous Pectoralis Major flap give good functional results. No infection or hemorrhage of mediastinal great vessels occurred. The indications of Anterior mediastinal tracheostomy are discussed. Stomal and peristomal recurrences following laryngectomy for carcinoma represents the indication of choice. Stomal recurrences are difficult to treat and the prognostic is poor. Prevention of the stomal recurrences is discussed. PMID- 4014937 TI - [Plastic surgery after circular pharyngectomy. Apropos of 78 cases]. AB - 78 patients with hypopharyngeal and/or cervical oesophageal squamous cell carcinoma underwent a total pharyngectomy from 1970 to 1982. The pharyngeal and/or cervical oesophageal reconstruction was carried out with cutaneous flaps, myocutaneous flaps or colon interposition. The advantages and disadvantages of these techniques as well as their complications are discussed. Following this experience, a therapeutic attitude is presented. The authors insist on the quality and duration of survival of patients after the surgical procedure. PMID- 4014938 TI - [Purulent meningitis after minor nasosinus surgery. Apropos of 10 cases]. AB - Purulent meningitis developed during the immediate or late postoperative period in 10 patients undergoing minor surgical procedures for nasosinusal affections. An important point is that the meningeal infection may be a very late onset complication, the osteodural gap sometimes giving rise to several attacks of meningitis at unexpected times. Treatment should be based on the presence or absence of clinical cerebrospinal fluid rhinorrhea, of a fracture of the anterior shelf of base of cranium on tomography, and results of isotopic scanning which are valid only if positive. Surgery to close the gap is justified when rhinorrhea persists after recovery from meningitis or when recurrent bouts are reported. Even after surgery, however, there is still the risk of further attacks of meningitis. An interesting adjuvant to treatment is by antipneumococcal vaccination. PMID- 4014939 TI - [Radiotherapy of carcinoma of the nasopharynx in children after previous chemotherapy. Preliminary results on 21 cases treated at the Institut Gustave Roussy between 1978 and 1981]. AB - Between 1978 and 1981, 21 children were treated at IGR for a poorly differentiated carcinoma of the nasopharynx. In hopes of diminishing the radiation doses and the incidence of metastases, the treatment began by either single agent or combination chemotherapy. The total dose of irradiation could be reduced to 50 Gy in 17 patients. The short term results are available for 18 cases. There were 2 isolated local recurrences, 2 isolated nodal recurrences and 1 combined local and nodal recurrence. In march 1983 the overall results revealed the following: of 21 patients initially treated, 10 are alive without local regional recurrence (but 1 with metastases); 2 are dead metastases; 9 are lost to follow up with metastases. PMID- 4014940 TI - [Total glossectomy with preservation of the larynx and immediate reconstruction. Apropos of 27 cases]. AB - Total glossectomy with preservation of larynx was performed in 27 patients with lesions affecting the whole tongue and developing from the base, the tonsilloglottal recess, of the junction zone and of the posterior wall, or from the mobile tongue. Results in patients followed up for more than one year (27 cases) showed: 11 survivors only, with 12 deaths from local, regional or metastatic recurrence. Among the 11 survivors, 7 presented very satisfactory functional rehabilitation--they no longer required tracheotomies, were free from pain and fed themselves without problem with mixed types of food. Phonation could be understood and they were reasonably autonomous. When tumoral excision is possible in patients with extension not evident as palpable glands, this operation appears quite justified for patients who are psychologically motivated and very insistent on some therapy, the modalities and risks of which have been exposed. PMID- 4014941 TI - Labyrinthine otosclerosis studied with a new computed tomography technique. AB - Forty-two patients (84 ears) with surgically confirmed otosclerosis were examined with a computerized tomographic scanner (Philips Tomoscan 310) equipped with a table swivel mechanism. All ears were scanned in the horizontal and a new semilongitudinal plane. In patients with an unimpaired bone conduction threshold, a normal labyrinthine capsule was found in all ears except two. Normal bone conduction does not exclude extensive labyrinthine otospongiosis. In cases with bone conduction impairment, the bony labyrinth appeared normal in about half the ears. In the other half, areas of bone resorption were present and a positive correlation was found between the degree of bone loss and the amount of bone conduction threshold loss. PMID- 4014942 TI - Clinical assessment of flap perfusion by fiberoptic fluorometry. AB - Perfusion fluorometry, a method which quantifies tissue fluorescence after intravenous fluorescein injection, has been highly predictive of skin flap survival in animals. It is advantageous because it is objective, simple, noninvasive, repeatable, and can be used to monitor flap perfusion constantly by following both uptake and elimination of dye. We applied this method clinically to a variety of flaps used in head and neck surgery. All flaps with good fluorometric values survived totally. Based on experience with 37 flaps, fluorometric indices have been established that accurately predict necrosis. Serial dye injections have been used to document transient flap ischemia in the early postoperative period. Representative cases illustrating the advantages of fluorometry in flap assessment are presented. PMID- 4014943 TI - Vocal function following carbon dioxide laser surgery for glottic carcinoma. AB - Vocal function following laser surgery for glottic T1a carcinoma was evaluated in 17 patients and compared to vocal function following radiotherapy in 14 patients. The results are summarized as follows. 1) A slight degree of hoarseness was found more frequently following laser surgery than following radiotherapy. The quality of hoarseness was rough and breathy in most cases. 2) In stroboscopic examination, incomplete glottal closure and diminution or lack of vibration of the operated vocal fold were frequently observed following laser surgery. 3) There was no marked difference in maximum phonation time, mean airflow rate, fundamental frequency range of phonation, intensity range of phonation, and intensity-flow ratio between the laser and the radiotherapy groups. On the basis of these results, we conclude that there is little difference in vocal function between postlaser and postradiotherapy patients as far as conversational voice is concerned. PMID- 4014944 TI - Auditory brain stem potentials recorded at different scalp locations in neonates and adults. AB - The auditory evoked brain stem potential was recorded in 14 normal full-term infants and nine normal-hearing adults. Silver-silver chloride electrodes were placed at nasion, forehead, vertex, each mastoid over the bony prominence, and the seventh cervical vertebra (noncephalic reference) in order to study the scalp distribution of the auditory brain stem response. Large differences in the scalp distribution between the newborn and adult populations were observed. At the ipsilateral mastoid, an x wave occurring at approximately 2 ms and a y wave occurring at approximately 3.3 ms were identified in the adult; this contrasts to a y wave at approximately 3.7 ms in the neonate. It appears that there are either separate generators for some of the components in the adult versus the neonate, and/or as the nervous system matures, myelinization occurs with a concomitant change in the scalp distribution of the auditory brain stem potentials. PMID- 4014945 TI - Petrous apicitis: surgical anatomy. AB - Various surgical approaches to the petrous apex for exposure and drainage of suppurative processes are available to the otologist. The petrous apex may be conveniently divided into anterior and posterior portions by a line in the coronal plane through the internal auditory canal. The approach to the posterior petrous apex follows fistulous tracts in the sinodural angle, the subarcuate fossa, and the infralabyrinthine tract. The anterior petrous apex may be entered by means of a radical mastoidectomy. Fistulous tracts into an infected anterior petrous apex may be found through the hypotympanum, below the cochlea, through a triangle anterior to the cochlea, below the middle fossa dura, and above the carotid artery. In this approach to the petrous tip, one must have a thorough knowledge of the anatomical relationships around the carotid artery and cochlea: the carotid artery lies within 1.69 +/- 0.70 mm of the cochlea anteriorly, and the carotid artery may be exposed within the middle ear. PMID- 4014946 TI - Effects of repeated stripping on vocal fold mucosa in cats. AB - Repeated stripping of the vocal folds in patients with recurrent vocal nodules may produce permanent, negative effects on voice quality. Hoarseness can be present with no evidence of structural or functional disease on indirect laryngoscopy. A common assumption is that scar tissue has formed, though the relationship between scarring and voice quality is not clear. In the study reported here, cats were subjected to four strippings of the left vocal fold at 6 to 8-week intervals. Tissues obtained were examined for changes in the composition of the mucosa and its nervous network. Alterations observed over the four strippings included 1) an increasing component of fibrous tissue and 2) apparent changes in both the number and structure of nervous elements. Implications of the findings for voice production, clinical management, and further research are discussed. PMID- 4014947 TI - Computerized tomographic evaluation of the middle ear and mastoid for posttraumatic hearing loss. AB - High resolution computerized tomography has been proven valuable in all aspects of temporal bone study. The importance of the procedure in evaluation of traumatic lesions, particularly of the middle ear, has been underemphasized. Damage to the middle ear may occur with blunt trauma, penetrating injury, or barotrauma. Conductive hearing loss and/or CSF otorrhea may result. Detailed evaluation of the ossicles is the hallmark of properly performed computerized tomographic evaluation. PMID- 4014948 TI - Venous hum as a cause of reversible factitious sensorineural hearing loss. AB - Self-heard venous hums have been previously documented and recognized as one cause of audible pulsatile tinnitus. A patient presented with a right internal jugular venous hum causing audible tinnitus and a right sensorineural hearing loss, both of which resolved after high ligation of the right internal jugular vein. We speculate that the hearing loss measured initially was factitious and represented a masking effect due to the venous hum. PMID- 4014949 TI - Squamous cell carcinoma of the middle ear. A 25-year retrospective study. AB - Squamous cell carcinomas of the middle ear cleft are highly unpleasant tumors which pose many problems for the otologist. We have retrospectively reviewed the hospital notes of 21 patients (22 ears) who presented with this disease in order to try to clarify those features which are of prognostic significance. We confirmed that a history of chronic suppuration with or without cholesteatoma predisposes the patient to tumor development and that, in the presence of continuing otorrhea, patients are not protected by mastoid surgery. These patients have been treated with conservative surgery and radiotherapy without en bloc resection of the temporal bone and, in these circumstances, the histological grade of the tumor at presentation appears to bear a direct relationship to survival. PMID- 4014950 TI - Brain stem auditory evoked potential monitoring during profound hypothermia and circulatory arrest. AB - The effects of decreased temperature on brain stem auditory evoked potentials (BAEP) have been previously described in mild to moderate hypothermia. This report describes BAEP monitoring during profound hypothermia (11 degrees C) and circulatory arrest for repair of an aortic arch aneurysm. Recording of BAEP were interpretable during cooling to 14 degrees C, and demonstrated increasing interpeak (I-V) latency compatible with prolongation of brain stem conduction time. The changes rapidly returned to normal during rewarming from profound hypothermia, in a fashion similar to that seen after mild hypothermia, and therefore appear to be completely reversible. PMID- 4014951 TI - Preservation of the human cochlea. AB - Human cochleas processed with a varying interval between death and initial fixation were examined by transmission and scanning electron microscopy. The specimens were fixed by paraformaldehyde-glutaraldehyde fixatives in buffer. Cochleas fixed less than two hours postmortem showed excellent morphology in general. With increasing time lag between death and fixation the results became more variable. In some specimens fixed up to six hours postmortem, however, the morphology still was well preserved, but as the interval increased, a greater variability was introduced. The conclusion is that specimens fixed up to six hours postmortem can show excellent electron microscopic morphology. Limited information can be obtained up to 12 hours postmortem, after which the results tend to be unreliable. PMID- 4014952 TI - Cochlear vessel permeability to horseradish peroxidase in the normal and acoustically traumatized chinchilla: a reevaluation. AB - A method involving incubation of intact cochleae using the small protein, horseradish peroxidase, has revealed that a barrier exists between the blood and the stria vascularis. This barrier is more tenuous than the barrier that exists across other cochlear vessels. The stria-strial vessel barrier can be altered physiologically by acoustic trauma or artifactually by dissection. PMID- 4014953 TI - Nerve fibers in the fetal organ of Corti. Scanning electron microscopic study. AB - Four human fetal inner ears ranging from 22 to 25 weeks' gestation were examined by scanning electron microscopy. Dissection of the organ of Corti revealed nerve fibers at the bottom of Corti's tunnel and the first row of the external spiral bundles on the medial wall of Deiters' cells. The nerve fiber arrangement was more complicated compared to that of animals so far reported. Thin nerve fibers which ran irregularly and showed branching were found both in Corti's tunnel and in the external spiral bundle and at times were connected to the tunnel medial fibers. These thin fibers were estimated to be efferent in nature. PMID- 4014954 TI - Effect of peroral glycerol administration on inner ear fluid electrolytes of guinea pigs. AB - After the oral administration of 50% glycerol (12 mL/kg), serum, CSF and inner ear fluids from scala tympani perilymph, scala vestibuli perilymph, and scala media endolymph were collected from normal guinea pigs under sodium pentobarbital anesthesia (25-35 mg/kg). The sodium and potassium concentrations were determined by microflame photometry. Increases in sodium concentrations were found in CSF, scala tympani perilymph, scala vestibuli perilymph, and cochlear endolymph. No significant change was observed in the serum. These sodium increases were considered to be due to the dehydration caused by the osmotic action of glycerol. Potassium concentration was increased only in scala tympani perilymph. Oral administration of glycerol was found to be more gradual and effective in dehydration compared to intravenous injection. PMID- 4014955 TI - [The carcinogenic role of earlier x-ray irradiation of multiple epitheliomas of the back. Critical study of 15 personal cases]. AB - The authors report 15 cases of multiple epitheliomas of the back, concerning patients who had been previously submitted to X-ray irradiations. Their cases are divided into two groups: the first comprises 11 patients who had undergone lumbar and sacral anti-inflammatory radiotherapy for rheumatologic diseases; the second concerns 4 patients who had had many fluoroscopic examinations for lung tuberculosis and later developed multiple epitheliomas of the back. For each group of patients, they detail the irradiation procedures, and indicate the interval before the subsequent tumoral development, as well as the histologic features. In both groups, basal cell epitheliomas prevail with any type of histologic pattern (mainly pagetoid, however). Fibroepithelial tumours of Pinkus are not more numerous in the lumbar area (on the contrary: 20 p. 100 against 28.57 p. 100). Precancerous keratoses and Bowen-like conditions are only found in the second group (in fact in a single patient). The important feature is not the topography but the dose of irradiation. Fourteen out of 15 patients had only basal cell epitheliomas and fibroepithelial tumours. PMID- 4014956 TI - [Cutaneous prickle-cell epitheliomas and visceral cancer]. AB - We have studied the incidence of internal malignant neoplasms on patients with squamous cell carcinoma (SCC). This incidence has been compared to expected number of malignant neoplasm in that population by a precise statistical analysis. Two-hundred and eighty-three SCC confirmed by histology are diagnosed on 235 patients (159 men, 76 women). These patients have been followed between December 1970 and November 1982 at the specialized consultation on cutaneous tumors. We have examined all these patients, questioned their doctors, consulted their medical case history, to search an internal malignant neoplasm. Twenty eight patients had a malignant neoplasm: this malignant tumor has been found 11 times before and 17 times at the same time or after SCC. These 17 malignant neoplasms are the only statistically interesting cases. The annual incidence of malignant neoplasms related to age and sex has been evaluated by consulting French registers. The French incidence has been compared to foreign incidences. This incidence enables us to calculate the expected observed numbers (12 and 5). The expected numbers are 9.15 for men and 2.1 for women. These numbers are not statistically different from observed numbers (12 and 5). The incidence of internal malignant neoplasms on patients with SCC is not different from the incidence of general population. PMID- 4014957 TI - [Lichen-hepatitis syndrome. General review apropos of a case]. AB - Recently some evidence has accumulated indicating that lichen ruber planus, especially in its erosive variety, may be an important indicant of chronic cirrhogenic hepatitis, either a chronic active hepatitis or a primary biliary cirrhosis. Usually the cutaneous lesions precede the obvious clinical features of liver disease by months or years and the erosive quality of the lesions usually indicates the presence of hepatic cirrhosis. A case is reported herein which had so typical features of both lichen planus and erosivus and chronic active hepatitis to be regarded as representative of this association. In Italy, possibly due to the high prevalence of hepatitis B virus infection, the lichen planus patients seem to have a higher probability to develop a chronic active hepatitis, whereas those in Great Britain and USA, for genetic reasons perhaps, seem to associate with primary biliary cirrhosis. The distinction of the two hepatic diseases is difficult in the earliest stage, but it is very important, because their treatments are quite different. The association lichen planus chronic active hepatitis appears not to be fortuitous and its possible pathogenetic mechanism is proposed. PMID- 4014958 TI - [Radical excision of giant abdominal nevi in infants. Apropos of 3 cases]. AB - Total removal of giant naevi with a minimal residual scar is of course ideal for prevention of malignancy and obvious psychological reasons. One can take advantage of the excess of skin existing in infants to be able to perform such wide excisions with immediate closure. Three cases of abdominal wall excisions in infants are presented, one of the upper abdomen at 9 months, two of the lower abdomen, at 3 months and 6 months. In all cases, a wide undermining was performed to allow the immediate closure. For the two lower abdominal excisions, preservation and transposition of the umbilicus were performed, like on an aesthetic abdominoplasty in adults. The blood loss was minimized by infiltration with epinephrine and meticulous hemostasis. Healing was uneventful. The scars, with a one to two years follow-up, are smooth and fine, and there are no change of contour. Progress in pediatric anesthesiology has resulted in the fact that a large excision and repair in infants presents no more potential dangers than operation performed later. Feasibility of such early wide excisions has been explored in other areas of the body; however, the abdominal wall is the area of choice. PMID- 4014959 TI - [Dermatitis caused by the manchineel tree]. AB - Contact dermatitis form Hippomane mancinella L. (manchineel) is commonly observed in Caribbean and Central American Coast land. Its sap from leaf exudate and from the fruit induce severe dermatitis that may involve oral, ocular, genital mucous membranes and skin, depending on the mediate or direct type of contact. Intense itching or burning sensation occurs within an hour and is followed by painful erythema, vesicles, bullae or pustulae, the latter being highly suggestive of mancheneel. Oropharyngeal and ocular lesions may by very severe. The brief delay and the burnlike appearance of the lesions suggest an orthoergic mechanism due to a caustic that could be similar to the substance identified in an other species of Euphorbiacae as phorbol esters. Traditional and native remedies are presented herein. PMID- 4014960 TI - [The multiple lentigines syndrome and elastic dystrophy]. PMID- 4014961 TI - [Pediatric cardiology, a specialty which, like many others, is evolving]. PMID- 4014962 TI - [Etiologic factors in congenital cardiopathies]. PMID- 4014963 TI - [Coarctation of the aortic isthmus. Current surgical technics in children]. PMID- 4014964 TI - [Management of aortic stenosis in children]. PMID- 4014965 TI - [Contribution of bidimensional echography in pediatric cardiology]. PMID- 4014966 TI - [Porcine valvular bioprostheses in children. Results in 40 patients]. PMID- 4014968 TI - Flow measurements with magnetic resonance. PMID- 4014967 TI - [Scorpion poisoning in children]. PMID- 4014969 TI - Magnetic resonance imaging of clots in the heart and vascular system. PMID- 4014970 TI - Some factors involving slice shape which affect contrast in nuclear magnetic resonance (NMR) imaging. PMID- 4014971 TI - Analysis of parenchymal opacification by digital angiography. PMID- 4014972 TI - Diagnostic and interventional procedures in the biliary tract. PMID- 4014973 TI - Functional imaging of blood flow. PMID- 4014974 TI - Digital angiographic technique for the quantitative assessment of myocardial perfusion. PMID- 4014975 TI - Angiographic evaluations on the influence of vasoactive drugs in renal vascular compartments. PMID- 4014976 TI - VIIIth congress of the European Society of Cardiovascular and Interventional Radiology and the VIth international postgraduate course of the European College of Angiography. 20-25 May 1984, Elsinore, Denmark. PMID- 4014978 TI - Jaundice in children--a spectrum of causes. PMID- 4014977 TI - Computed tomography diagnoses of eye tumors and anomalies in early childhood and infancy. PMID- 4014979 TI - Therapeutic embolization of hemangiomas and hemangioendotheliomas of the liver in infants. A hemodynamics study. PMID- 4014980 TI - Magnetic resonance (MR) imaging of aorta and pulmonary circulation. Initial experience with ECG-gating. PMID- 4014981 TI - Cardiosynchronous MRI intensity changes of the great vessels and pulmonary circulation. A preliminary report. PMID- 4014982 TI - Cardioangiography in children with iohexol, metrizoate and ioxaglate. PMID- 4014983 TI - Nuclear magnetic resonance evaluation of fifty children with cancer. PMID- 4014984 TI - [Experimental study on the predation of Cionella lubrica Muller by Nesovitrea hammonis Strom]. AB - The predation of C. lubrica by N. hammonis was studied under controlled laboratory conditions. Adult N. hammonis ate mainly prey measuring 2 to 4 mm in height. The predation rate was steady in spite of the increase in number of predators for the same number of prey. Vegetable food was indispensable to N. hammonis' predation. The predation was maximum at 20-25 degrees C. N. hammonis cannot be considered as an agent of biological control against C. lubrica owing to its limited predation. PMID- 4014985 TI - [Interference between anthelmintics and immunity in gastrointestinal strongylosis of sheep]. AB - Groups of very similar sheep (breed, sex, age, hemoglobin type, family) were immunised against H. contortus by repeated infections. Self-cure and immune reactions expelled parasites but some of them still remain in the gut of animals; they have been eliminated by dosage of anthelmintics. Animal were challenged; a discrepancy exists between numbers of eggs passed in each group (immune and dosed animals, immune and non-dosed animals and non-immune animals); the best fitting estimated equation on experimental values (or on moving average points) is used for statistical tests. Immunity vanishes partly (or totally) when animals have been dosed; a residual population of worms is thought to be responsible for immunity because of a permanent booster. PMID- 4014986 TI - Study of gastro-intestinal strongylosis in a sheep flock on permanent pasture 2. Sheep parasitism in 1978-1979. AB - The epidemiological study carried out in 1977 in the Limousin region of France was continued for the next two years. Eighty-five lambs were slaughtered at the rate of five animals every weeks: sixty were slaughtered from May 1978 to March 1979 and twenty-five from May to September 1979. Total parasite counts and coprological examinations were carried out. In spring the infestation of the lambs was early and heavy, and revealed that certain free-living stages can survive in low temperatures. The pattern of development of the parasites differed according to the year. It was concluded that control programmes based on theoretical patterns of evolution of the parasite will need profound study of climatic variations. Three species were found most frequently: Ostertagia circumcincta, Nematodirus spp. and Trichostrongylus colubriformis. Haemonchus contortus, exceptionally numerous in 1977, did not return to its normal level until 1979. A significant correlation was demonstrated between the number of eggs per gram of faeces and the number of female adult parasites. Thus the usefulness of coprological examinations in the diagnosis of ovine digestive strongylosis was proven. In spite of relatively high parasitism, no significant difference was found over the two years between the weight gains of regularly treated and untreated lambs. PMID- 4014987 TI - [Short review on the causative agent of scrapie]. PMID- 4014988 TI - In vitro metabolism of zeranol: evaluation of covalent binding to microsomal protein. AB - Using an in vitro system (i.e. bovine liver microsomes), the authors have studied the metabolism of zeranol. The oxidation of zeranol into zearalanone by NADPH dependent monooxygenases has been measured. The rate of metabolic activation and the level of covalent binding to microsomal proteins of zeranol metabolites have been evaluated. They were found to be very low. A possible detoxication effect of glutathione and glutathione-S-transferases was undetectable. PMID- 4014989 TI - [Control of antroduodenal motility in sheep]. AB - The continuous but cyclic delivery of contents through the pylorus in the adult ruminant is regulated by the initiation of the migrating myoelectric complexes on the duodenal bulb. The motor responses of the pyloric antrum to the volume of digestive contents, the presence of lipids and ulcerogenic agents revealed that the inhibition of the motor antral activity, whatever its origin, resulted in a higher frequency of the duodenal cyclic motor events. Conversely, stimulation of duodenal motor activity, for example the increased frequency of migrating myoelectric complexes, resulted in the inhibition of the antral motor activity. It is suggested that the motor profile of the antroduodenal junction corresponded to interactions which fulfill the regulation of gastric emptying motor functions, with the first part of the duodenum as an extremely sensitive and rapid controlling mechanism. PMID- 4014990 TI - Naturally-occurring Tyzzer's disease (Bacillus piliformis infection) in commercial rabbits: a clinical and pathological study. AB - Tyzzer's disease has been detected in nine unrelated, commercial rabbitries. During the acute stage of the disease, recently weaned rabbits showed profuse watery diarrhoea. Mortality was between 14.2 and 41.2% during the first three weeks of the outbreaks. In surviving animals, there was a chronic evolution with depression, anorexia, loss of weight and sometimes extreme cachexia. Reproduction animals were less badly affected. Multifocal hepatic necrosis, focal myocardial necrosis, patches of mucosal necrosis in ileum, caecum and colon and marked caecal oedema were most prominent at autopsy. In histological sections of the liver, bundles of slightly Gram-negative and Giemsa-, PAS- and silver-positive rod-shaped bacilli were established in apparently viable hepatocytes bordering foci of necrosis. They were also present in myocytes around necrotic foci in the heart and in enterocytes and smooth muscle cells of the muscularis mucosae of the intestinal mucosa. Transmission electron microscopy showed that these organisms had a similar ultrastructure as Bacillus piliformis. Most antibiotics used failed to combat the disease. Only oxytetracycline was active. PMID- 4014991 TI - [Experimental paratuberculosis: biological diagnosis in calves inoculated with strains of mycobactin-dependent mycobacteria]. AB - During an experiment on the pathogenicity of mycobactin-dependent mycobacteria strains for calf, the kinetics of antibody formation during infection was studied. The progress of cellular immunity was followed by examining delayed hypersensitivity using four allergens (bovine tuberculin HCSM, avian tuberculin HCSM, avian tuberculin PPD, and johnin PPD), and that of humoral immunity using complement fixation test and ELISA. Simultaneously, the elimination of bacilli in the faeces was examined. The excretion of bacilli, although intermittent, appeared to be the most demonstrative proof of infection: it could be shown at any stage of the disease. On the contrary, the delayed hypersensitivity using the avian tuberculin, and the serologic tests (the complement fixation test and ELISA), were positive only at defined periods of the disease: hypersensitivity reactions developed earlier than humoral reactions. The results obtained during these experiments confirmed that the mycobactin-dependent strains of "wood pigeon" mycobacteria caused a disease in calves similar to the disease caused by Mycobacterium paratuberculosis. PMID- 4014992 TI - Uraemia in the mare: effects of seasonal variations, of energy level of the diet and individual differences. AB - Uraemia variations in the heavy breed mare were studied in different situations. A study with 35 mares during an entire grazing season was conducted. The mean uraemia varied between 48.5 and 67.5 mg/100 ml plasma, with season and type of grass. The highest values were found with first-cycle pasture grass. Uraemia was lower with winter diets: 28.6 to 36.0 mg/100 ml. A study using 15 mares fed isonitrogenous diets based on hay or straw, and concentrates offered two different levels, between two months before and 8 days after foaling, showed that the physiological stage had a very moderate effect on uraemia, but that it was higher with a low concentrate level (35.6 to 44.0 mg/100 ml plasma from one period to another) than with a high concentrate level (25.8 to 33.3 mg/100 ml). An analysis on two herds of 7 and 5 mares sampled 9 times during a whole year showed that the individual effect is highly significant. It could not be explained by age differences. These measurements have further defined some sources of variation other than the nitrogen concentration of the diet. PMID- 4014993 TI - Free and conjugated zeranol residues determined by radio-immunoassay in urine and plasma of calves treated with Forplix. AB - Anti-zeranol 7-hemisuccinate-bovine serum albumin was raised in rabbits. This antiserum was used in a radio-immunoassay of zeranol residues in urine and plasma of calves implanted with Forplix. The antibody was specific for zeranol but cross reacted with its metabolite zearalenone and the mycotoxin zearalenone. Detection limits in plasma and in urine were 100 pg/ml and 1 ng/ml respectively. In veal calves treated with zeranol containing implant, no residues were detected in plasma even if plasma proteins were hydrolysed with pronase before the radio immunoassay. Free and conjugated residues in urine were easily measured. The urine concentration of conjugated residues increased markedly after the 20th day of treatment and was still high (19 ppb) at day 40. PMID- 4014994 TI - Trichostrongylus colubriformis: relationship between ageing of infective larvae, infectivity and egg production by adult female worms. AB - Relationships between egg production and infectivity were studied with infective larvae of Trichostrongylus colubriformis which had been stored for up to 22 weeks at 24 degrees C. After different storage times, larvae were administered to lambs and the number of parasites which reached the adult stage was counted five weeks after infection. Egg production was estimated for the same batches of animals by performing a quantitative coproscopic examination from the third week of infection onwards. Infectivity was maximum and constant during the first six weeks of storage and then decreased regularly from the 9th week to the end of the experiment. However, the number of eggs produced per female worm was constant during the first 6 weeks then doubled and remained constant from the 9th to the 22nd week of storage. PMID- 4014995 TI - Standard residue regulations for chloramphenicol in Spain. PMID- 4014996 TI - [Chloramphenicol in veterinary medicine. Authorization requirements for marketing]. PMID- 4014997 TI - Chloramphenicol in the Dutch situation. PMID- 4014998 TI - [Chloramphenicol: viewpoint and regulations in Switzerland]. PMID- 4014999 TI - The veterinary use of chloramphenicol in the United Kingdom. PMID- 4015000 TI - [Criteria for the use of chloramphenicol in breeding farms in Italy]. PMID- 4015001 TI - [Mechanical prostheses or bioprostheses?]. PMID- 4015002 TI - [Valve replacement. Criteria other than age in the choice of a prosthesis]. PMID- 4015003 TI - [Long-term outcome of mechanical prostheses]. AB - The insertion of mechanical valve prostheses has transformed the particularly severe natural history of certain valve diseases. The inherent complications of the valve decrease the quality of these results. Thromboembolic and haemorrhagic complications remain the major drawbacks of mechanical prostheses. These risks are reasonable for the aortic orifice, especially with well adapted anticoagulant treatment, but many authors prefer bioprostheses for the mitral orifice. PMID- 4015004 TI - [Clinical and hemodynamic evolution of Carpentier-Edwards prostheses]. PMID- 4015005 TI - [Long-term outcome of bioprostheses]. AB - The major advantage of cardiac bioprostheses, apart from the good haemodynamic performance of recent models, is that they are not thrombogenic, so that the patient does not have to follow a life-long anticoagulant treatment. However, their major disadvantage, in comparison with the mechanical prostheses, is that they deteriorate over time. This study defines the durability of bioprostheses over the first seven years and beyond seven years. During the first seven years, if we compare the risk of thromboembolic and haemorrhagic complications of anticoagulant treatment to the risks of tissue deterioration, there is a clear advantage in favour of the bioprostheses. However, this is only true in adults, as in patients under the age of 20, the bioprostheses deteriorate much more rapidly. Few statistics are available concerning the followup of bioprostheses beyond seven years. However, on the basis of these statistics, absence of deterioration was observed in 75% of cases at 9 years and in 65% of cases at 10 years. These figures demonstrate that the great majority, if not all, cases of bioprostheses implanted at the present time will not need to be changed before 8 to 15 years. These results justify the research currently underway in various centres to determine the cause of these deteriorations and to try to prevent them. PMID- 4015006 TI - [Thromboembolic accidents in patients with mechanical prostheses and heterografts]. AB - 759 patients with a prosthetic valve replacement (335 mitral prostheses, 184 aortic prostheses and 240 double or triple valve replacements) were regularly followed-up for a total duration of 3 715 patient years. The mean age of these patients was 30 years. 681 (90%) of these patients were treated by long term anticoagulants, which were effective in only 320 patients. 78 patients did not receive anticoagulant treatment. 97 patients presented a total of 129 thrombo embolic episodes (TEE), i.e. a frequency of 12.7 p. cent or 3.4 embolisms per 100 patients-year. The rate of TEE was influenced by the site of the prosthesis and by the presence or absence of complete arrhythmia due to atrial fibrillation, but it was not influenced by the quality of the anticoagulant treatment. In the patients with a heterograft, the rate of TEE varied according to the site of the prosthesis. In the aortic position, the rate of TEE in our series of prostheses was essentially similar to that reported in series of heterografts by Davila, Oyer and lonescu. This rate is generally higher for the mechanical prostheses in the mitral position and in the case of double valve replacement. The aim of this study was to deduce the current operative indications in relation to the choice of the type of valve replacement. PMID- 4015007 TI - [Valve replacement in children and adolescents. Bioprosthesis or mechanical valve?]. PMID- 4015008 TI - [Diagnosis of thromboses of aortic and mitral valve prostheses. Treatment by fibrinolytic agents]. PMID- 4015009 TI - [Choice of a valve prosthesis in patients between 25 and 70 years of age]. AB - In patients over the age of 70, the choice is unanimously in favour of a bioprosthesis. In children and adolescents, the rapid deterioration of bioprostheses makes them unsuitable for these patients. However, between the ages of 25 and 70, the situation is much more open to discussion. In the aortic orifice, because of the low risk of thrombo-embolism, there is a preference for a mechanical valve, except in the case of a young woman wishing to have a child or in the case of a contraindication to anticoagulants. In the mitral orifice, the higher incidence and the greater severity of the thrombo-embolic complications present an argument in favour of bioprostheses, which should be selected in the case of anticoagulant risks (contraindication, exposure to trauma, impossibility of following a female patient who wishes to become pregnant), in the case of a high thrombogenic risk (ectatic thrombosed left auricle or replacement of a thrombosed prosthesis) and, finally, the preference of the patient and the doctor. The bioprosthesis is unequivocally indicated in the case of tricuspid valve replacement. PMID- 4015010 TI - [Prognosis of myocardial infarction. Introduction]. PMID- 4015011 TI - [Prognosis of the acute stage of myocardial infarction. Rhythm factors]. AB - At the present time, it is still difficult to determine the real prognostic significance of cardiac arrhythmias in the acute phase of myocardial infarction. The metabolic and electrogenic consequences of myocardial ischaemia are responsible for the principal mechanisms involved in the development of arrhythmias in the ICU: conduction disorders and/or ventricular arrhythmias. Based on a review of the literature, the author analyses the prognostic value of the principal arrhythmias: branch block, atrio-ventricular block, primary ventricular fibrillation and repetitive or isolated ventricular extrasystoles. A number of conclusions can be drawn from this study: isolated arrhythmias in the acute phase are a sign of metabolic and electrolyte disorders and only influence the immediate prognosis. The same arrhythmias, associated with anatomical damage, altered myocardial function or heart failure, may be the sign of severe, long term complications. The development of arrhythmias in the acute phase of infarction should not be interpreted in isolation, but together with the results of further investigations to test the value of the myocardium and the electrical instability. The patient's real risk can only be evaluated on the basis of all of these findings. PMID- 4015012 TI - [Cardiac manifestations of chronic atrophic polychondritis]. AB - The authors present a case of chronic atrophic polychondritis with cardiovascular complications, consisting of aortic incompetence due to dilatation of the aortic ring associated with an aneurysm of the ascending aorta and a first degree atrio ventricular block occurring six months after the onset of the disease. The progression towards heart failure resulted in the replacement of the ascending aorta and of the aortic valve. The authors discuss the cardiovascular complications of this disease. PMID- 4015013 TI - [Evaluation of the severity of coronary disease by thallium 201 myocardial scintigraphy and technetium 99m isotope ventriculography. Comparison of the 2 methods apropos of 30 cases]. AB - The evaluation of the severity of coronary artery disease by non-invasive methods may involve the use of isotope techniques. The authors compared the results of technetium 99m cardiac functional angioscintigraphy and thallium 201 myocardial scintigraphy, performed at rest and on effort, in a group of 30 patients. The 30 patients consisted of 6 normal patients (control group) and 24 patients with coronary artery disease (8 cases of angina; 16 infarcts, including 12 inferior infarcts). Coronary angiography revealed 13 cases of one vessel disease, 8 cases of two vessel disease and 3 cases of three vessel disease. The results of angioscintigraphy revealed that the technique was reliable in terms of the evaluation of the abnormalities of contraction (sensitivity: 96%, compared with the results of haemodynamics) and that the study of the ejection fractions at rest and on effort was particularly valuable. The ejection fractions calculated by the isotope method were not statistically different from the ejection fractions calculated by the haemodynamic method. The patients with one vessel disease and the normal subjects increased their ejection fraction on effort by about 12% (p = 0.03), in contrast with the patients with multiple vessel disease, who increased their ejection fraction on effort by 2% (p greater than 0.05). In contrast, the results of myocardial scintigraphy at rest and on effort were disappointing. The method was specific (100%), but in our series, its sensitivity was only 72% for the group of patients with coronary artery disease. In cases with infarction and multiple vessel disease, the zone of the infarction was always detected, but no other abnormalities were observed in the other territories.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4015014 TI - [Iatrogenic internal mammary arteriovenous fistula. Apropos of 2 cases]. AB - Two fairly similar cases of internal mammary arterio-venous fistula were observed in two patients involved in serious road accidents, following which a catheter was inserted into the subclavian vein for the purposes of resuscitation. The clinical diagnosis was made in both cases on routine examination, which revealed a continuous right subclavian bruit with extensive radiation three years after the accident. There were no functional implications. Further investigations revealed a fistula located between the internal mammary artery and the right brachiocephalic venous trunk and demonstrated the haemodynamic consequences: normal intra-cardiac pressures, but a pulmonary blood flow which was twice that of the systemic blood flow. Both cases were treated by means of surgical cure via thoracotomy, which confirmed the nature of the arterio-venous fistula and which defined the relations with the phrenic nerve, which is the most exposed element. The results of this operation were excellent in both cases. PMID- 4015015 TI - [An overlooked electrocardiographic sign of acute embolic cor pulmonale: elevation of the ST segment in right precordial leads]. AB - Elevation of the ST segment in the right precordial leads may be associated with electrocardiographic signs of acute cor pulmonale. This sign, which we have observed in 77 cases of moderate to severe pulmonary embolism (greater than 1.3 per cent of cases), is a very early but transient sign of usually moderate to severe pulmonary embolism. In the presence of this sign, the diagnosis of pulmonary embolism with acute cor pulmonale should be proposed at the same time as more common aetiologies such as coronary insufficiency and pericardial disease. PMID- 4015016 TI - Causes of death in patients previously operated on for primary hyperparathyroidism. AB - Out of 334 patients operated on for PHPT in the years 1956-79, 34 (10.2%) had died before the end of the year 1980. In the sex and age matched control material of 334 patients operated on at the same time for varicose veins, appendicitis or haemorrhoids the mortality was 21 (6.3%). The difference in mortality between these groups was statistically significant (p less than 0.05). The mean age at death of the PHPT patients was 65 years and that of the control patients 67 years. The PHPT patients who died differed from the whole PHPT material in higher mean age at operation (61 years v. 53 years), higher preoperative serum calcium values (3.31 mmol/l v. 3.08 mmol/l), more frequently elevated serum creatine preoperatively (44% v. 17%) and higher mean weight of the removed adenomas (3300 mg v. 2000 mg). The PHPT patients who died had also more often the severe form of PHPT: 55% of the patients with hypercalcaemic crises and 24% of the patients with cystic bone changes had died, whereas the respective percentage was 4% in the renal stone group. Four of the PHPT patients had died of uraemia, and, in addition, four patients had progressive renal damage. 18 PHPT patients had died of cardiac disease, four patients of a cerebrovascular attack and one patient of other vascular disease. There were eight cardiovascular deaths in the control group (p less than 0.01). There were no differences in other causes of death, such as malignant tumours, between the groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4015017 TI - Fractures of the distal forearm in the Helsinki district. AB - The incidence and some epidemiological features of fractures of the distal forearm in the Finnish population are described. An annual incidence of 36.5 per 10 000 was calculated for the population over 15 years of age. The incidence seems to vary within wide limits according to the season, and the patient's age and sex. The highest numbers were noted in women of 60-70 years of age. However, these marked differences in incidence are less evident in cases treated as in patients. The figures do not differ much from those for Oslo, but are higher than those for Sweden or Great Britain. PMID- 4015018 TI - Long term results of late reconstruction for anterior or anteromedial instability of the knee. AB - Forty-one patients who had had surgical repair for anterior or anteromedial instability of the knee were examined on average 3.7 years after the operation. Of these patients, 17 had been injured in sports activities, 11 in work accidents, 5 in traffic accidents and 8 during other activities. Twenty-six patients underwent intra-articular reconstruction of the anterior cruciate ligament where the Jones procedure was used, 7 with the HeyGroves procedure, and 2 by the Eriksson procedure. The remaining 6 patients were treated by transfer of the gracilis, semitendinosus tendon or fascia lata. During the operation, the medial collateral ligament was reefed in 4 knees and Mauck's reconstruction was performed on 4 knees. Medial meniscectomy was carried out in 9 patients. The results were evaluated using subjective, functional and objective criteria. The objective criteria included both clinical examination and stress radiography using a specially designed apparatus. Laxity of the medial collateral ligament and anterior drawer sign were recorded on radiographs, using the uninjured knee for comparison. The operation was estimated to have been successful subjectively (excellent or good) in 25 patients, functionally successful in 20 and objectively successful in 23 patients. In the personal opinion of 33 patients the knee improved. Meniscectomy and long follow-up time were found to cause a decrease in successful results. More arthritic changes appeared if meniscectomy had been performed. The patients returned to work within an average period of 3.7 months. In 7 cases the result was classified as functionally poor, and the knee required a subsequent operation. PMID- 4015019 TI - A broncho-biliary fistula probably due to exacerbation of chronic pancreatitis. A short review of the literature. AB - Broncho-biliary fistulae are generally secondary to echinococcal abscesses in the liver, less frequently to trauma, penetrating or not. A third group seems to follow biliary tract obstruction, surgical or non surgical. Congenital broncho biliary fistulae seem to be extremely rare. We present here a case of broncho biliary fistula probably secondary to an exacerbation of chronic pancreatitis. Liberal surgical drainage, safe closure of the diaphragm and early surgical intervention are mandatory and are emphasized. PMID- 4015020 TI - Semisurgical treatment of giant condylomata. AB - A semisurgical method to treat giant condylomata acuminata is described. Several silk ligatures are placed on the tumourous mass. Complete recovery was found to occur even in very extensive lesions. The procedure proved to be safe, neither bleeding, late scarring, nor local recurrence were observed. PMID- 4015021 TI - Spontaneous rupture of vaginal enterocele. AB - Spontaneous rupture of an enterocele is a rare complication. Only 24 cases including the present case have been reported in the literature. The patients were elderly and had had at least one vaginal operation. The patients were remarkably unaffected symptomatically on admission. PMID- 4015022 TI - Acute appendicitis as primary symptom of gastric cancer. PMID- 4015023 TI - Acute cholecystitis. Frequency of stones in the common duct and predictive value of liver function tests. AB - Two hundred and forty-three patients aged under 75 years with acute calculous cholecystitis treated by early surgery were studied with a view to investigating the frequency of choledocholithiasis and the predictive value of routine liver function tests (bilirubin, alkaline phosphatase, alanine aminotransferase). 7% had stones in the common duct, but 33% had hyperbilirubinaemia. In less than 10% of the latter could be hyperbilirubinaemia be attributed to common bile duct stones. It was concluded that the frequency of common bile duct stones in acute cholecystitis was low, and that patients often had signs of impaired liver function which was of no help in diagnosing the presence of stones in the common duct. PMID- 4015024 TI - Coffee and the heart. PMID- 4015025 TI - Variation of estrogen and progesterone receptor status in breast cancer. AB - In a series of fifty breast cancer patients two estrogen and progesterone receptor assays were performed. In two simultaneous assays (tissue samples taken at the same time) disordant results in estrogen receptor, progesterone receptor and double receptor status were detected in 12%, 12% and 21% of cases respectively. In sequential assays (tissue samples taken with an interval between the samples) this variation was more pronounced, 24%, 36% and 36% respectively. The variation in simultaneous assays was similar between two samples of the same primary tumour as between samples from a primary tumour and a metastasis. In sequential assays there was no difference in the time between assays in concordant and discordant samples. The variation in receptor status is said to be due to the heterogeneity within the primary tumour. PMID- 4015026 TI - Rheumatoid factor seroconversions in relation to clinical rheumatoid arthritis. AB - Two blood samples were taken with an interval of five years in a continuing epidemiological study of a rural population with an age range of 40-64 at the commencement. Paired sera from 1805 subjects were tested for rheumatoid factors using Waaler-Rose and latex tests. Simultaneous conversion in both tests from negative to positive occurred in seven cases and from positive to negative in eight cases, corresponding to 20% of the Waaler-Rose positives. The mean Waaler Rose titre in the cases converting to positive was nearly four times higher than in the cases converting to negative. Five subjects developed Waaler-Rose-positive rheumatoid arthritis after the baseline survey. In three of them, positive rheumatoid factor reactions were observed to precede the joint disease; in two others the chronological order could not be established. PMID- 4015027 TI - The 125I-labelled fibrinogen uptake test in elective hip surgery. AB - The value of the 125I-labelled fibrinogen uptake test as a screening method for deep vein thrombosis was estimated in 49 patients (97 extremities) undergoing elective hip operations. The legs were monitored preoperatively, on the 1st, 2nd and 4th postoperative days. Contrast venography, as a reference method, was performed on the 5th postoperative day. The sensitivity was 73%, specificity 85%, positive predictive value 63%, negative predictive value 86% and correlation coefficient 55%. 78% of fibrinogen uptakes appeared within the first 24 hours, and 6% on the 4th postoperative day. Only 1 of 3 patients with a positive fibrinogen uptake test in the femoral region had roentgenologic evidence of deep vein thrombosis. According to these results the isotope-labelled fibrinogen uptake test can also be utilized as a screening method in elective hip surgery. PMID- 4015028 TI - Orthostatic tolerance at different times of the day in physically average and very fit dayworkers. AB - We studied the relationship between the physical exercise capacity and the orthostatic tolerance of physically average fit and very fit dayworkers at different times of the day. Six male railroad workers were physically very fit and six were averagely fit (mean of the maximal oxygen consumption 57.4 and 34.6 ml.kg-1.min-1, respectively. The mean age was 32 years. The orthostatic tests were performed with a tilt-table at 2.00, 6.00, 10.00, 14.00, 18.00, and 22.00 hours on six different days. Orthostatic lability at night was seen in both groups. At 14.00 and 18.00 hours the orthostatic tolerance in average fit men was slightly lower than in very fit men. This difference in the orthostatic tolerance between the groups may be a sign of the interdependence of good exercise tolerance and orthostatic tolerance. PMID- 4015029 TI - Gastritis, duodenogastric reflux and bacteriology of the gastric remnant in patients operated for peptic ulcer by Billroth I operation. AB - Of 101 patients undergoing Billroth I gastrectomy (BI) 14 years previously, we were able to investigate 39. General abdominal symptoms, haematological status, basal (BAO) and maximal (MAO) hydrochloric acid secretion were studied before (I) and 1 year (II) and 14 years (III) after the operation. Stump mucosa morphology was investigated before the operation and 14 years afterward. Duodenogastric reflux with radioisotope and fasting bile reflux methods and stump bacteriology were studied at the last follow-up and compared with those of controls who had had peptic ulcer 15 years ago. Only 10% of the operated patients could be classified as Visick Grade III, the others being Grades I-II. At the time of the follow-up, mean body weight had not changed. Serum iron was better at 14 than one years after the operation. BAO and MAO decreased significantly after the operation, but these decreases did not continue during the postoperative period. Duodenogastric reflux was significantly greater in the gastrectomized patients than in the controls. Neither the progression of gastritis nor the degree of postoperative gastritis correlated with the reflux. Of the operated patients, 6% had normal stump mucosa and 80% had atrophy. From the stump we cultured colonic bacteria in 44% of the patients, pharyngeal flora in 71% and Candida in 56%. The stomach bacteriology of the controls was: 10% colonic, 35% pharyngeal flora and 30% Candida. The general status of BI-patients remains good. Although gastritis progresses to atrophy and duodenogastric reflux increases, the reflux and atrophy do not seem to be related. In spite of increasing atrophy hydrochloric acid secretion continues. PMID- 4015030 TI - A morphological approach to the problem of the biological similarity of Jewish and non-Jewish populations. AB - The genetic kinship between various Jewish and non-Jewish groups, from the biochemical standpoint, has been much investigated, frequently with very contradictory conclusions. The present paper reports the results of two comparative analyses of several Jewish and non-Jewish populations as based on morphological measurements of adult males. The first analysis employed data on Jewish and non-Jewish communities from five geographic regions of the world. The dendrogram resulting from the cluster analysis clearly indicates that Jewish populations are much closer to one another than to non-Jewish neighbour groups. In the second analysis, 25 ethnoterritorial groups of the USSR (one Jewish and the rest non-Jewish) were evaluated on the basis of 27 anthropometric characters. The latter Jewish group was markedly separate from the other 24 ethnic groups, and especially distinct when only traits with high coefficients of heritability were employed. PMID- 4015031 TI - Palmar pattern reduction among the Bushmen. AB - Hand prints from 98 male and 57 female !Kung Bushmen, who show the characteristic high frequency of digital arches observed in other Bushmen samples, also show attenuation of dermatoglyphic patterns in the third interdigital area. There is an acceptable level of reproducibility between independent observers using Hauser's semi-quantitative scoring method for interdigital pattern reduction. Interdigital reduction forms are more frequent than those reported in Vienna, but their associations are similar, and so is the relationship of the bc count to the total reduction score. As the degree of reduction increases in the third interdigital area, mainline terminations tend to be located more radially. The results provide a further demonstration of the interrelatedness of dermatoglyphic traits. PMID- 4015032 TI - Effect of altitude on the physical growth of upper-class children of European ancestry. AB - The physical growth of 351 upper-socioeconomic-status children (9-20 years) of European ancestry residing in La Paz, Bolivia (altitude 3600 m) is described and compared with that of lowland children of similar background. The purpose is to evaluate the independent effect of continual exposure to atmospheric hypoxia during the period of growth and development on linear growth. The data presented here indicate that the effect of hypoxia on achieved stature ranges from minimal in males and none in females to a maximum of 3 cm in both sexes. The magnitude of this effect is relatively small compared to the potential effect of other factors which affect the growth of highland children. PMID- 4015033 TI - The application of new height-prediction equations (Tanner-Whitehouse mark 2) to a sample of Canadian boys. AB - The adult statures of a sample of 71 Canadian boys from the Saskatchewan Longitudinal Growth Study were predicted using the original TW Mark 1 and the new TW Mark 2 prediction equations. The subjects had a mean chronological age of 11.59 years (SD = 0.30), a mean RUS bone age of 11.62 'years' (SD = 1.18), a mean height of 145.0 cm (SD = 6.98) and a mean measured adult height of 177.2 cm (SD = 6.65). The Mark 2 equations improved the predictions over Mark 1 by an average of 0.2-0.6 cm and slightly reduced the range of errors. No improvement in the prediction of boys above the 75th centile of British standards was noted but 60 70% of boys below the 25th centile predicted better with the Mark 2 equations. This pattern may well be repeated in more extreme subjects. About 80% of individuals who predicted badly with the Mark 1 equations, i.e. with errors equal to or greater than 5 cm, improved their predictions when Mark 2 equations were used. PMID- 4015034 TI - Population structure and blood genetics of the Pacaas Novos Indians of Brazil. AB - Two communities of relatively recently contacted Brazilian Indians, the Pacaas Novos, have been studied in relation to several demographic parameters and 28 genetic systems. The age and sex distribution, fertility and mortality patterns were not very distinct in the two populations, but they differed markedly in relation to the mating, migration and genetic data (six of the 19 variable loci showed differences higher than 10%). This was interpreted as being the consequence of a fission event, one of the many that may periodically occur, sometimes followed by fusions, in populations at this cultural level. The Pacaas Novos also show some distinctive features when previous genetic studies of South American Indians are reviewed, eight alleles of the variable 19 (LMS, R2, R0, Se, Hp1, Gm1,2;21, Gc1F and PGM1(1)), presenting differences varying between 12%-34% from the average obtained considering these earlier investigations. PMID- 4015035 TI - Inbreeding and fertility in a South Indian population. AB - Among 1913 women in Karnataka State, South India, 37.74% had married a relative (a consanguineous union), 60.79% were non-consanguineously married, and 1.46% did not know whether they had married a relative. Mean number of living offspring for consanguineously married women who had completed their reproduction was 3.89, and for the non-consanguineous 4.07. There is no significant difference in the mean level of fertility for the two groups measured in this way. Pre-natal mortality is lower (but not significantly) among consanguineously married women who have completed their reproduction than among the non-consanguineous group, but post natal mortality is significantly higher among the conceptuses of the consanguineously married women. Although consanguineously married women conceive more frequently, that is, are more fecund than the non-consanguineous women (mean number of conceptions being 6.61 and 6.28, respectively), the difference is not significant. The differential survival of the offspring results in the consanguineous group having slightly lower net fertility, although the difference is not statistically significant. The lower sterility rates of the consanguineously married women (3.21% of all consanguineously married women show primary sterility compared to 3.47% of the non-consanguineous) may be due to greater compatibility of uniting gametes in the consanguineous marriages. The data reveal that women married to a relative and having completed their reproduction show higher fecundity, lower pre-natal mortality, higher post-natal mortality, lower sterility rates, and thus no significant difference in net fertility to those who had not married a relative. PMID- 4015036 TI - Androgyny in fat patterning is associated with obesity in adolescents and young adults. AB - Recent work suggests that android or male-type obesity is characterized by fat cell enlargement on the trunk and upper body. This implies adult differences in patterns of body fat distribution may have developmental origins connected with differences in maturation or age of onset of obesity. To investigate this, we studied adolescent females (N = 455, 12 years), males (N = 527, 14 years) and young adults (N = 393 females and N = 413 males, 17 years) of the US Health Examination Survey. Five skinfolds and five maturity indicators were available. Individuals were classed as normal weight, overweight or obese on the basis of the body mass index (WT/HT2). Fat patterning was studied by principal components analysis of the log residual skinfold thickness at the five sites, which revealed trunk/extremity and upper/lower trunk fat distribution components in all sex/age groups studied. The means of both components were significantly (P less than 0.05) greater in obese than in normal weight individuals indicating that obesity in adolescence and young adulthood consists of fat concentrated on the upper aspect of the trunk. The effect was independent of maturity, which was a significant correlate of the trunk/extremity patterning component only and in males only. Advanced physiological maturity is probably not a determinant of adult patterns of body fat distribution, but obesity which occurs in adolescence may be. PMID- 4015037 TI - Linear regressions in the calculation of lethal gene equivalents in man. AB - Linear regressions have been used extensively for the calculation of lethal gene equivalents in human populations. There are considerable theoretical and practical objections to the use of the method for this purpose. PMID- 4015038 TI - Antineoplastic activity of planar rhodium(I) complexes in mice bearing Lewis lung carcinoma and P388 leukemia. AB - The antitumor effects of three rhodium(I) complexes were evaluated using two transplantable tumors of the mouse: Lewis lung carcinoma and P388 lymphocytic leukemia. The examination of the differential effects on primary tumor growth and on the formation of spontaneous pulmonary metastases, in mice bearing Lewis lung carcinoma, indicated that the complex having qualitatively the higher solubility in aqueous solutions and the higher resistance to inactivation via oxidation, displayed the more pronounced antineoplastic activity. The antileukemic effects, in mice bearing P388 lymphocytic leukemia, also seemed to depend on the chemical characteristics of the complex used, and the previously reported trend was particularly evident using an acute treatment performed 24 hr after tumor transplantation. PMID- 4015039 TI - Influence of a prostaglandin synthesis inhibitor and of thrombocytopenia on tumor blood flow and tumor vascular permeability. Experimental studies in the rat. AB - The intratumor distribution of vascular permeability in two transplantable rat tumors was studied by calculating tissue-plasma ratios of two intravenously injected labeled albumins with an interval of five hours between albumin injections. The data were calculated and presented as the capillary permeability surface area product (PS) in multiple tumor biopsies. Furthermore, the intratumor distribution of blood flow was studied by the intratumor uptake of intravenously injected 86Rb. The same parameters were also studied in normal striated muscle. Prolonged administration of a prostaglandin synthesis inhibitor, diclofenac sodium (Voltaren) changed significantly the tumor blood flow towards higher values. A similar change was observed in animals with induced thrombocytopenia. Tumor PS values were increased by administration of diclofenac-sodium, but not by induced thrombocytopenia. The intratumor distribution of plasma volume, calculated from tissue-plasma values of albumin injected 5 minutes before the animals were killed, was not significantly changed as well as blood flow, plasma volume and PS in normal muscle. There was no significant correlation between separate tumor blood flow and PS values, while such a significant correlation was found in normal muscle. The observations made in this study suggest that a release of both prostaglandins and serotonin might be included in the regulation of tumor blood flow and vascular permeability. PMID- 4015040 TI - Effects of a calcium-antagonist (flunarizine) on cancer cell movement and phagocytosis. AB - Flunarizine, a calcium-antagonist drug that binds to calmodulin, was found to inhibit the migration of both B16 melanoma cells and M5076 macrophage-like cancer cells. The migration movement, both under agarose and through a polycarbonate filter membrane, was impaired by the drug. In M5076 macrophage-like cells Fc dependent as well as Fc-independent phagocytosis were also found significantly reduced by flunarizine. Results are discussed in relationship with the previously observed effects of the drug on the growth rate of B16 melanoma cells in vitro. PMID- 4015041 TI - Dietary habits and eating related symptoms in out-patients following total gastrectomy and Roux-en-Y reconstruction for carcinoma of the stomach. AB - Dietary habits and eating related symptoms were studied by one week recording method in thirteen successive out-patients attending the routine control following total gastrectomy and Roux-en-Y reconstruction for carcinoma of the stomach. All the patients except one had daily eating related symptoms such as difficulties in swallowing or/and rapid filling of the stomach, or/and discomfort, meteorism and pain, or/and nausea, faintness, sweating and rapid pulse. The number of daily meals was high (eight to fifteen) and the amounts of food eaten small, consisting of one sandwich, or one fruit, or one glass of milk, especially in those patients with most symptoms and most frequent meals. The daily intake of energy (7.4 +/- 2.0 and 6.8 +/- 1.5 MJ in the males and females, respectively) and nutrients was low, and there were no differences between the daily energy intakes by the patients with eight or fifteen daily meals. Thus, it is concluded that in the out-patients following total gastrectomy and Roux-en-Y reconstruction for carcinoma of the stomach, the symptoms related to eating are common and frequent, what causes the high number of daily meals and decreases the quality of life of the patients. The meals of the patients are simple and the patients are prone to a reduced nutritional state due to the low intake of energy and nutrients. PMID- 4015042 TI - Effects of local microwave hyperthermia and 5-fluorouracil in treatment of experimental liver cancer. AB - The effect of combined treatment with local hyperthermia and i.v. infusion of 5 fluorouracil was studied in 39 Wistar rats with a transplanted adenocarcinoma inoculated in the liver. Ten to 13 days later the rats were divided into three groups. Group A1 was subjected to local microwave hyperthermia (42 degrees C) for 1 h. During the hyperthermia, an i.v. infusion of 5-FU (20 mg/kg body weight) was given. In group A2 5-FU was administered under normothermic conditions. Group A3 received saline infusion under normothermic conditions. The mortality after infusion of 5-fluorouracil and hyperthermia increased during the first week after treatment. In group A1, a significant growth retardation of liver tumor was registered seven days after treatment. This effect was not superior to that of hyperthermia alone as previously described for the same experimental model. Studies of 5-FU pharmacokinetics in plasma were performed in another 20 Wistar rats. Ten rats were given an i.v. infusion of 5-FU during local hyperthermia, while the other 10 were infused under normothermic conditions. Plasma concentration of 5-FU was determined by isotachophoretic separation. The hyperthermia caused a faster decline in serum concentration of 5-FU, probably because of accelerated catabolism of the drug. PMID- 4015043 TI - Treatment of acute non-lymphocytic leukemia in Saitama Cancer Center. AB - Forty patients with previously untreated acute nonlymphocytic leukemia (ANLL) were treated at Saitama Cancer Center between February 1979 and November 1983. Their median age was 43 years (range: 14 to 68 years), 13 patients (32.5%) being 55 years old or older. Twenty-three patients had Auer bodies. Complete remission was achieved in 75.0% of the patients (30/40) with the first line therapy, and in 6 of 7 patients in the second line therapy. Thus, the overall remission rate was 90.0%. The median duration of remission was 14 months and 39% of the patients showed no relapse within 3 years. The median survival for all patients was 26 months and the actuarial 3-year survival rate was 41%. The better results in this series were thought to be due to intensive post-induction reinforcement therapy. PMID- 4015044 TI - Effects of dimethyltriazenes combined with surgery and non-specific immunotherapy in mice bearing Lewis lung carcinoma lines. AB - The therapeutic efficacy of the preoperative administration of DTIC and its benzenoid analog DM-COOK, in terms of prolongation of the life-span of mice bearing Lewis lung carcinoma lines with different metastatic potential, has been evaluated in combined experiments with surgery and postsurgical non-specific immunotherapy with the peptidoglycan monomer PGM. The effects of the presurgical selective antimetastatic treatment with the dimethyltriazenes consist of a statistically significant prolongation of the survival time of the treated mice. The activity is more pronounced, in terms of animals cured, using the tumor line which is endowed of a low ability to colonize the lungs. The addition of postsurgical immunotherapy with PGM improves the overall therapeutic efficacy of the combined treatment with triazenes and surgery, independently from the tumor line used. In general, the presurgical treatment with the benzenoid triazene DM COOK, causes antineoplastic effects slightly better than those observed using the imidazole derivative DTIC. PMID- 4015045 TI - Antiestrogen binding sites in human breast cancer biopsies. Measurement ligand specificity and affinity, and correlation to estrogen and progesterone receptors. AB - Specific binding sites for the antiestrogen tamoxifen (AEBStot), as measured with the dextran-coated charcoal technique and Scatchard analysis, were quantitated in 43 of 44 breast cancer samples (41-2,100 fmol/mg protein). In this work, AEBStot has been defined as the sum of AEBSspec and estrogen receptor (ER), AEBSspec shows a very weak positive correlation with ER, and no correlation with progesterone receptor. Tamoxifen (TAM) has a lower affinity to ER compared with one of its main metabolites, 4-OH-TAM. This may be one reason why inhibition by excess estradiol on 3H-4-OH-TAM binding was better correlated with ER content in the same sample than if 3H-TAM was the radioactive ligand. It is therefore suggested that 3H-4-OH-TAM is a better choice than 3H-TAM for measuring AEBSspec alone. A possible role of AEBSspec for the clinical effects of TAM is discussed. PMID- 4015046 TI - [Congenital diverticula and valves of the anterior urethra]. AB - Basing themselves on fourteen personal cases, the authors propose a distinction between two types of congenital lesions obstructing the anterior urethra--valves and diverticula. The main difference between the two resides in the fact that, while diverticula develop outside the corpus spongiosum, the prevalvular distension, in the case of valves, is covered by it. Valves must be treated by endoscopic resection, and this procedure gave good results in all three cases in which it was followed. A surgical approach to a valve through the walls of the urethra involves a risk of late severe stenosis. Diverticula have been successfully managed surgically in a single operation by ablation followed by reconstruction of the urethra. Attempts to treat them by endoscopic resection of the anterior border of the diverticulum were unsuccessful. Three diverticula were non-obstructive, and a cowperian origin was probable in two cases. PMID- 4015047 TI - [Monseur one-stage urethroplasty in the correction of anterior urethral stenoses]. AB - Urethral dilatation, internal urethrotomy both blind and endoscopical for treatment of strictured male anterior urethra are neither always successful nor without complications. Free full thickness patch grafts of skin and island grafts described for one-stage urethroplasty have their specific indications and are not devoid of complications. Monseur in 1968 described his technique of one-stage urethroplasty which was used in this work in 22 cases. Their age ranged between 18-60 years. None of them was complicated by fistulae, and their follow-up for 36 months excluded recurrence of the stricture. PMID- 4015048 TI - [A non-secreting bladder paraganglioma. A case report]. AB - The authors report the case of a 43 year old patient hospitalized for hematuria extending over eight years. Cystoscopy revealed an endovesical lesion which was resected and diagnosed as a non-secreting vesical paraganglioma. At operation, the cervical localization of the lesion was treated by total cystoprostatectomy. Starting out from this case report, the authors discuss the difficulties of diagnosing non-secreting vesical paragangliomas, the difficulties of assessing their malignancy and therefore the difficulties of treating them. PMID- 4015049 TI - [Thyroid metastases from a nephro-epithelioma]. AB - The authors report a rare case of thyroid metastasis from a nephro-epithelioma, which appeared four years after nephrectomy, and was revealed by a Basedow-type goiter. It was treated by total thyroidectomy. A cervical recurrence was diagnosed in the course of a routine checkup and arteriography. Death occurred 22 years after thyroidectomy and 26 years after nephrectomy. The diagnosis is often only made at necropsy. The slow growth of these metastases does not preclude extended survival after surgical excision, and requires active therapy. PMID- 4015050 TI - [Calcium oxalate monohydrate (whewellite) renal lithiasis]. AB - Pure calcium oxalate monohydrate lithiasis is rare--about 5 to 10% of total renal lithiases. The proportion is the same in men and women. Pure calcium oxalate stones are a polished dark brown color, and are very hard. They are visualized radiologically as regular and homogeneous. From a biological standpoint, this type of stone is frequently associated with normal calciuria and oxaluria. Pure calcium oxalate monohydrate stones rarely evolve. PMID- 4015051 TI - [Increase in urinary uric acid in the rat following portacaval shunt. The action of clofibrate]. AB - Two successive experiments on rats confirm that a portocaval shunt leads to a substantial increase in uricosuria, which does not climax in the first week postoperatively. Clofibrate, an inductive liver enzyme, significantly reduces the uricosuria, but only after a certain timelag. Uricosuria, the degree of which varies with individual rats, leads to crystallization of uric acid, mainly in the form of ammonium urate, but polyuria secondary to portocaval shunt tends to inhibit the crystallization. A reduced water intake one day out of two facilitates the crystallization after a portocaval shunt. PMID- 4015052 TI - [Is iatrogenic vesico-renal reflux a negligible factor in the evolution of recurrent superficial tumors of the bladder?]. AB - The electrocoagulation and resection of superficial tumors of the bladder leads to iatrogenic refluxes. The frequency of subsequent vesical recurrences may thus favor tumoral grafts in the upper urinary tract. Fives cases illustrate this risk. They were treated by ureteral resections and by one bilateral, and two unilateral nephroureterectomies. Should these refluxes be ignored or treated surgically in the event of repeated papillomatous recurrences? PMID- 4015053 TI - [Total prostatocystectomy followed by enterocystoplasty in the treatment of bladder neoplasms]. AB - Bladder replacement enterocystoplasty in the treatment of bladder tumors provides the patient with maximum mictional comfort, and better protection of the kidneys than in the case of cutaneous urinary diversion. The remote carcinological results are satisfactory at over 60% nowadays at three years, against only 20%, seventeen years ago. The functional impact on continence is very good during the day but not yet satisfactory at night, but a sometimes lengthy re-education can help. The result on the upper urinary tract is still the delicate point in this technique, with the hope of an attenuation of the renal insufficiency thanks to the setting up of an antireflux process. However, the indications for this brilliant technique may be limited by the extension of the tumor and the fragility of the diasthesis. PMID- 4015054 TI - [Reabsorption of the irrigation solute during percutaneous nephrolithotomy]. AB - The publication of several accidents, possibly due to the reabsorption of irrigation solutions in the course of percutaneous nephrolithotomy, prompted the authors to quantify the amounts of glycine (1.50 per cent glycocol) reabsorbed in these operations, and to determine the metabolic consequences. In a prospective study of twelve patients subjected to fourteen percutaneous nephrolithotomies, the hemodilution parameters (natremia, protidemia, hematocrit and osmolality) and the amino acid content of the plasma were measured preoperatively, at operation, and immediately postoperatively. The study indicates that there is a hemodilution and reabsorption of irrigation solute comparable to that observed in transurethral resections of the prostate. The resultant hyperglycinemia probably explains the significant increase in ammonemia noted in all the patients. One theory is that hepatocellular insufficiency may increase this ammonemia. This might suggest the advisability of using saline solution, at least in these patients (that is, of course, in the absence of electrical lithotrity). PMID- 4015055 TI - [Obstetrical vesicovaginal fistulas in Africa. Apropos of 57 cases]. AB - The authors describe their experience in the surgical treatment of fifty seven cases of complex vesicovaginal fistulas, and advocate the plastic procedure used. PMID- 4015056 TI - [Duplication of the bladder by a frontal septum. Apropos of a case]. AB - The authors report a case of total bladder duplication by frontal septum. The anterior bladder was functional. The posterior bladder was non-functional, and drained a destroyed kidney. Analysis of the rare cases reported in the literature suggests that this malformation should be differentiated from other bladder duplications, because it may be a giant ureterocele. In conclusion, the authors stress the simplicity of the management, consisting of resection of the septum and nephrectomy of the non-functional kidney. PMID- 4015057 TI - [Balanopreputial hypospadias]. AB - Magpi's technique is described. It is an excellent procedure for the cure of the majority of cases of coronal or just subcoronal hypospadias, but its use is contra-indicated in the presence of a very large meatus, a thin, transparent, distal urethra, or a deeply grooved glans. In these cases, other techniques are required. PMID- 4015058 TI - [Macrotetrolide antibiotics from mycelia of Streptomyces chrysomallus]. AB - White crystalline antibiotically active substances identified as macrotetrolides were isolated from the mycelium of four actinomycetous strains, i.e. S. chrysomallus var. I, S. chrysomallus var. III, S. chrysomallus var. carotenoides and S. chrysomallus var. macrotetrolidi. The component composition of the macrotetrolide antibiotics of all four strains was identical. It was characterized by predominance of nonactin, a lower homologue. The composition ratio was the following: 69-79 per cent of nonactin, 19-29 per cent of monactin, 1-3 per cent of dinactin and the traces of trinactin and tetranactin. The strains differed in the intensity of production of the macrotetrolides and the ability to synthesize other biologically active substances. PMID- 4015059 TI - [Mechanisms of bacterial inactivation as affected by cation surface-active substances]. AB - The death kinetics and ultratructure of gram-positive and gram-negative bacteria exposed to alkyldimethylammonium chloride were studied. It was shown that at low concentrations (0.0001 per cent) the agent had a pronounced bactericidal effect, which was higher with respect to the gram-positive bacteria. Impairment of the intactness of the cytoplasmic membrane, a vitally important organoid of the bacterial cell, was the main factor in the mechanism of action of the cationic surface-active substance. Membrane structures of various configuration and localization not associated with the cell division were detected in the cytoplasm of the dead bacteria. These structures are probably the result of self-assembly of the membrane lipid components broken under the action of the detergent. PMID- 4015060 TI - [Synergistic effect of rifampicin on hepatotoxicity of isoniazid]. AB - It was shown in experiments on male albino rats that rifampicin potentiated the hepatotoxicity of isoniazid. As compared to the use of isoniazid alone, its combination with rifampicin resulted in a higher activity of transaminases and alkaline phosphatases and a higher rate of inhibition of biliary secretion and synthesis and excretion of bile acids, bilirubin and cholesterol with bile. Moreover, an increase was observed in the level of lipid peroxidation products of the hepatocyte membranes in liver homogenates and blood, which was indicative of an increased intensity of lipid peroxidation. The increased hepatotoxicity of isoniazid was evident from a more pronounced decrease in the number of sulfhydryl groups accompanied by an increase in the number of disulfide ones in the liver and blood. The authors suggest that potentiation of isoniazid hepatotoxicity under the action of rifampicin was due to its inducing activity with respect to the microsomal oxidation enzymes. PMID- 4015061 TI - [Decrease of sisomicin nephrotoxicity as affected by cephalothin: pharmacokinetic evaluation]. AB - The effect of cephalothin on the nephrotoxicity and pharmacokinetics of sisomicin was studied on Wistar rats. Sisomicin was injected intramuscularly in doses of 12.5 and 25 mg/kg alone or in combination with cephalothin in a dose of 360 mg/kg once a day for 16 days. It was shown that the combined use of sisomicin and cephalothin resulted in less pronounced functional and morphological changes in the kidneys as compared to the use of sisomicin alone. The decrease in the nephrotoxic effect was accompanied by a decrease in the sisomicin concentration in the blood serum and the site of the nephrotoxic effect (the kidney cortical layer) and the period of the aminoglycoside half-life in the kidney cortical layer under the action of cephalothin. The analysis of the relation between the nephrotoxic effect and the concentration of sisomicin in the kidney cortical layer and blood serum demonstrates that the nephrotoxicity of the sisomicin combination with cephalothin is mainly due to a decrease in the aminoglycoside concentration in the zone of the nephrotoxic effect. PMID- 4015062 TI - [A method of quality control of 3-phenyl-5-methylisoxazole-4-carbonic acid chloranhydride using high performance liquid chromatography]. AB - A method of quantitative determination of 3-phenyl-5-methyl-isoxazole-4-carbonyl chloride useful for its qualitative estimation at all stages of oxacillin industrial synthesis was developed. The methods is based on transformation of this semi-product into isopropyl ester followed by high efficiency liquid chromatography with the use of the "Milikhrom" chromatograph mad in the USSR. A variant of the typical method for determination of 3-phenyl-5-methyl-isoxazole-4 carbonyl chloride concentration in solution is described. PMID- 4015063 TI - [Ampicillin pharmacokinetics in pregnant women with acute pyelonephritis]. AB - The pharmacokinetics of ampicillin was studied in 38 patients with acute pyelonephritis in the second and third trimesters of pregnancy after the first and the last (28th-32nd) intramuscular injections of the antibiotic. The ampicillin levels in the blood and urine were determined with the agar diffusion method. The pharmacokinetic parameters were estimated in a one-compartmental model by computer The ampicillin levels in the blood and urine of the patients did not practically differ at all the investigation periods (0.5-6 hours after the antibiotic administration) in the second and third trimesters of pregnancy. During the treatment, the rate of ampicillin elimination from the host increased and the period of half-elimination from the blood decreased. The antibiotic levels in the urine within 4-6 hours after the last injection were practically lower in the second trimester of pregnancy as compared with the second trimester. The therapy resulted in an increase in the antibiotic renal clearance, which returned to normal in the second trimester of pregnancy and remained under normal in the third trimester of pregnancy. The increase was due to an approximately 2 fold acceleration of the rate of ampicillin secretion by the renal tubules. The total clearance of ampicillin practically increased in the second trimester of pregnancy and remained decreased in the third trimester of pregnancy. The estimation performed in accordance with the Krueger-Timmer principles on the basis of the characteristic features of the pharmacokinetics of ampicillin shown in the study provides recommendation of the following scheme for pyelonephritis treatment in pregnant women: 500 mg of ampicillin injected intramuscularly every 6 hours followed by gradual decreasing of the intervals between the injections to 4 hours as the rate of ampicillin elimination increases. PMID- 4015064 TI - [Effect of bile on bacterial sensitivity to antibiotics]. PMID- 4015065 TI - Effects of apalcillin on platelet function in normal volunteers. AB - We investigated the effects of apalcillin on blood coagulation and platelet function. The drug was administered to 21 human volunteers in daily intravenous doses of 75, 150, and 225 mg/kg. These doses evoked abnormalities in platelet aggregation similar to those found with piperacillin and mezlocillin and less striking than those produced by carbenicillin and ticarcillin. Plasma coagulation as measured by prothrombin time, activated partial thromboplastin time, thrombin time, and fibrinogen concentration was not affected. There were consistent and major reductions in plasma antithrombin III activity, particularly at the two higher dose levels. Of 21 patients, 7 (33%) also manifested maculopapular skin rashes which resolved after discontinuation of the drug. PMID- 4015066 TI - Inhibitory effects of chlorpromazine on Candida species. AB - Chlorpromazine was tested for antifungal activity by using Candida albicans and standard assays. The MIC of chlorpromazine was 35 micrograms/ml; the minimal fungicidal concentration was also 35 micrograms/ml. The minimal effective concentration was 2.2 to 3.5 micrograms/ml (using assays based on quantitative cultures and growth). There was a slight positive interaction between chlorpromazine and amphotericin B but no interaction between chlorpromazine and rifampin. Chlorpromazine also inhibited C. krusei, C. parapsilosis, C. tropicalis, and Torulopsis glabrata. We conclude that phenothiazines have direct anti-Candida activity and that these drugs appear to have a broad antimicrobial spectrum. PMID- 4015067 TI - Antibacterial action of colistin (polymyxin E) against Mycobacterium aurum. AB - Mycobacterium aurum was susceptible to the antibiotic colistin (polymyxin E),which had an MIC of 5 micrograms/ml and an apparent bactericidal effect at concentrations above 50 micrograms/ml. Treatment of actively growing cells with sublethal concentrations of colistin (15 micrograms/ml) resulted in synchronized cell division once the antibiotic was removed. Under conditions of synchronized cell growth, one cycle of DNA replication lasted 120 min and one cycle of cell division lasted about 180 min. Although the antibiotic treatment during synchronization experiments did not produce apparent changes in the bacterial envelope, it was accompanied by the accumulation of a polysaccharide-like substance in the bacterial cytoplasm which gradually decreased after the removal of antibiotic and by an increase in the number of mesosomes at 3 h after antibiotic removal. This step was closely linked to the doubling time of bacteria. Lethal concentrations of colistin of 50 and 100 micrograms/ml, which caused about 90 and 99% cell death, respectively, produced significant cytoplasmic membrane injuries, patchy appearance of the cell wall outer polysaccharide layer, and little cell lysis. These data indicate that the cytoplasmic membrane is a site of action of colistin and raise a question as to whether an outer bilayer exists in mycobacteria, at least functionally. PMID- 4015068 TI - Effect of pentobarbital anesthesia on amikacin concentrations in plasma and perilymph and evaluation of multiple sampling in perilymph of guinea pigs. AB - The purpose of this study was to determine whether a multiple-sampling procedure could be used in guinea pigs to study the kinetics of amikacin in perilymph. Amikacin was infused intravenously for 6 h into conscious anesthetized guinea pigs, and the concentrations of the drug in plasma and perilymph were measured. From each anesthetized guinea pig, five to six perilymph samples were collected from one ear, and one sample was collected from the other ear at 6 h. The concentrations of amikacin in perilymph were dose proportional and increased slowly during the 6-h infusion. However, after 6 h of intravenous infusion, the concentrations of amikacin in perilymph of the multiply sampled ears were significantly higher than those of the singly sampled ears, indicating that the multiple-sampling procedure should not be used as is to study the kinetics of amikacin in perilymph. Amikacin concentrations in perilymph were linearly related to amikacin concentrations in plasma in pentobarbital-anesthetized animals, as had previously been observed for conscious guinea pigs. However, the slope of the regression line was only 0.09 for anesthetized animals compared with 0.24 for conscious animals. Drug concentrations in plasma were found to be threefold higher in anesthetized animals, whereas drug levels in perilymph were the same in both groups at similar dosing rates. These results indicate that the amikacin concentration in perilymph is not solely dependent upon its concentration in plasma and that other factor(s) can affect the entry of amikacin into the inner ear. PMID- 4015069 TI - In vitro activity of Sch 34343 and cefbuperazone against anaerobic bacteria. AB - The in vitro activities of Sch 34343, a new penem antibiotic, and cefbuperazone, a new cephamycin antibiotic, were determined against 459 clinical anaerobic bacterial isolates and compared with the activities of imipenem and cefoxitin, respectively, by an agar dilution method. Both penems showed potent and similar activity against all anaerobic bacteria tested, particularly Peptococcus spp., Bacteroides fragilis, and Clostridium perfringens. All organisms except a single strain of Fusobacterium necrogenes were inhibited by an 8 micrograms/ml concentration of either Sch 34343 or imipenem. Overall, gram-positive bacilli, particularly Lactobacillus species, Clostridium difficile, and Bifidobacterium and Actinomyces species, were relatively more resistant to either penem than other genera of anaerobic bacteria tested. Cefbuperazone demonstrated only modest activity against a wide spectrum of anaerobic bacteria. It had excellent and selective activity against B. fragilis and Bacteroides vulgatus but was highly inactive against Bacteroides distasonis and Bacteroides thetaiotaomicron within the B. fragilis group. Both cephamycins showed virtually no activity against C. difficile and Lactobacillus spp. Although cefbuperazone was more active against Bifidobacterium spp., it had less activity against Fusobacterium spp., Eubacterium spp., and all Bacteroides spp. other than B. fragilis and B. vulgatus. PMID- 4015070 TI - Analysis of amifloxacin in plasma and urine by high-pressure liquid chromatography and intravenous pharmacokinetics in rhesus monkeys. AB - An analytical method for the quantitation of amifloxacin, 6-fluoro-1,4-dihydro-1 (methylamino)-7-(4-methyl-1-piperazinyl)-4-oxo-3- quinolinecarboxylic acid, in plasma and urine has been developed. The method involves extraction with chloroform, back-extraction into 0.1 M sodium hydroxide, and subsequent analysis by reverse-phase high-pressure liquid chromatography with UV detection. The precision of the assay calculated as the overall standard deviation was +/- 4.9% in plasma and +/- 1.1% in urine. The range of mean percent differences from the nominal values was used as an estimate of accuracy and was 93.6 to 103% of the nominal values in plasma and 95.2 to 107% of the nominal values in urine. The minimum quantifiable levels were 0.032 micrograms/ml in plasma and 2.7 micrograms/ml in urine. The methods were employed in a pharmacokinetic analysis of amifloxacin after intravenous administration to rhesus monkeys. The decline in drug plasma levels was described by a biexponential process with mean rates of 8.4 h-1 and 0.32 h-1 with corresponding half-lives of ca. 5 min and 2.2 h. Amifloxacin was rapidly excreted, with ca. 53% of the dose appearing in the urine within 48 h after medication. The mean renal clearance +/- standard deviation was 4.4 +/- 1.0 ml X kg-1 X min-1 and is compatible with passive glomerular filtration in this species. PMID- 4015071 TI - Metabolism and disposition of amifloxacin in laboratory animals. AB - Sprague-Dawley rats received [14C]amifloxacin mesylate either orally or intravenously at 20 mg (base equivalent) per kg. Blood radioactivity peaked at 0.5 h after oral administration and was equivalent to 7.54 micrograms/ml for males and 6.73 micrograms/ml for females. After intravenous administration to rats, 52.5% of the dose was recovered in the urine of males and 45.3% in the urine of females within 72 h. The corresponding values after oral administration were 50.8% for males and 37.2% for females. The remainder of the dose was recovered in the feces. After intravenous administration of [14C]amifloxacin mesylate at 10 mg (base equivalent) per kg to female rhesus monkeys, 80.3% of the radioactivity was excreted in the urine at 24 h. The apparent first-order terminal elimination half-life of intact amifloxacin in plasma was 2.3 h; radioactivity in plasma was eliminated more slowly. Male rats excreted 26.2% of the dose in the urine as amifloxacin and 17.8% as the piperazinyl-N-oxide derivative of amifloxacin after intravenous administration. The corresponding amounts for female rats were 29.0% as amifloxacin and 7.8% as the piperazinyl-N oxide metabolite. Similar excretion profiles were observed after oral administration. After intravenous administration, female monkeys excreted 54.5% of the dose in the urine as amifloxacin, 12.9% as the piperazinyl-N-desmethyl metabolite, and 5.6% as the piperazinyl-N-oxide during the first 12 h. In contrast, there was no evidence of the piperazinyl-N-desmethyl metabolite in rats. PMID- 4015072 TI - Relationship between rat renal accumulation of gentamicin, tobramycin, and netilmicin and their nephrotoxicities. AB - Gentamicin, tobramycin, and netilmicin were given to rats in daily doses of either 5 or 20 mg/kg for 30 days to determine the renal accumulation kinetics of the compounds and to correlate steady-state renal parenchymal concentrations with nephrotoxicity. Four rats from each group were sacrificed daily and renal parenchymal tissue concentrations were determined microbiologically. Nephrotoxicity was assessed by changes in creatinine values in serum, renal creatinine clearances, and pathological scores. There was no indication of aminoglycoside-induced nephrotoxicity in any tests performed. The following steady-state levels resulted: 36, 148, and 176 micrograms/g after 5 mg/kg per day and 148, 260, and 510 micrograms/g after 20 mg/kg per day for tobramycin, gentamicin, and netilmicin, respectively. We conclude that aminoglycoside parenchymal accumulation in rats follows this order: tobramycin less than gentamicin less than netilmicin. Therefore, differences in the relative toxicities of gentamicin, tobramycin, and netilmicin do not correlate with the renal parenchymal accumulation of these agents and may be more dependent on intrinsic toxicity to the renal proximal tubule than to the concentration of the aminoglycoside in the kidney. PMID- 4015073 TI - Structural similarities of the staphylococcin-like peptide Pep-5 to the peptide antibiotic nisin. AB - The staphylococcin-like peptide Pep-5 was shown to be a complex mixture of closely related and strongly basic peptides. Five peptides were purified by high pressure liquid chromatography on reversed-phase and gel filtration columns and further characterized by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and amino acid analysis. Four peptides have molecular weights of ca. 3,500, whereas one is of double size. All contain the thioether amino acid lanthionine and a large number of lysine residues per molecule. The amino terminus of the main active peptide is blocked; the carboxy-terminal end is formed by a lysine residue. The data obtained for Pep-5 suggest striking structural similarities to the peptide antibiotics nisin and subtilin. PMID- 4015074 TI - Mode of action of the peptide antibiotic nisin and influence on the membrane potential of whole cells and on cytoplasmic and artificial membrane vesicles. AB - The peptide antibiotic nisin was shown to cause a rapid efflux of amino acids and Rb+ from the cytoplasm of gram-positive bacteria (Staphylococcus cohnii 22, Bacillus subtilis W 23, Micrococcus luteus ATCC 4698, and Streptococcus zymogenes 24). It strongly decreased the membrane potential of cells as judged by the distribution of the lipophilic tetraphenylphosphonium cation. Ascorbate-phenazine methosulfate-driven transport of L-proline by cytoplasmic membrane vesicles was blocked after addition of nisin, and accumulated amino acids were released from the vesicles. Soybean phospholipid (asolectin) vesicles were not affected by nisin. The data suggest that the cytoplasmic membrane is the primary target and that membrane disruption accounts for the bactericidal action of nisin. PMID- 4015075 TI - Effect of temocillin and moxalactam on platelet responsiveness and bleeding time in normal volunteers. AB - The effects of temocillin and moxalactam on platelet responsiveness and bleeding time were examined in healthy male volunteers. In the first study, moxalactam (4 g intravenously every 12 h) was given to six subjects; template bleeding times were at least doubled in five subjects 12 to 14 h after 7 doses (P = 0.008) and in all six subjects 12 to 14 h after 13 doses (P = 0.004). ADP-induced primary aggregation was approximately halved after 7 (P = 0.026) and 13 doses (P = 0.008), and there was a markedly increased tendency toward disaggregation. Collagen-induced aggregation was also halved, but the effect only reached statistical significance after 13 doses (P = 0.008). There was essentially no effect on primary aggregation in response to the thromboxane receptor agonist U46619 or to platelet activating factor. Temocillin (4 g intravenously every 12 h) was given to eight subjects, three of whom had participated in the moxalactam study 8 weeks earlier. Temocillin had no significant effect on template bleeding time 12 to 14 h after 7 or 13 doses. However, in four subjects, the endpoint may have been less abrupt. There was no significant effect on ADP-induced primary aggregation or responsiveness to collagen. Even after 13 doses of temocillin, secondary aggregation in response to normal concentrations of ADP was demonstrable in the platelet-rich plasma of all eight subjects. Neither antibiotic had any effect on prothrombin times. Thus, with methodology that readily detected the effects of moxalactam on hemostasis, we were unable to demonstrate any unequivocal deleterious effects of temocillin at its maximum recommended dose. Temocillin may therefore be particularly useful for the treatment of many gram-negative infections in patients at increased risk of clinical bleeding. PMID- 4015076 TI - Role of the phosphoroclastic reaction of Clostridium pasteurianum in the reduction of metronidazole. AB - To demonstrate the importance of electron siphoning by the metronidazole reductase system from reduced ferredoxin to the mechanism of action of the drug in Clostridium pasteurianum, the effects of the reduction of metronidazole on the phosphoroclastic reaction were studied. Metronidazole concentrations between 0.5 and 5 mM caused a significant increase in acetyl phosphate production by the phosphoroclastic reaction compared to the control system without metronidazole. When this enzymatic reaction was assayed by standard manometric techniques under nitrogen gas, two simultaneous effects of electron siphoning were demonstrated: (i) the electrons from reduced ferredoxin were initially consumed for the reduction of metronidazole instead of being evolved as H2 via the ferredoxin linked hydrogenase and (ii) phosphoroclastic activity was stimulated, with augmented production of CO2 and acetyl phosphate. This work further supports the notion of preferential scavenging of electrons away from ferredoxin-linked enzymatic reactions by metronidazole reductase(s) in C. pasteurianum. PMID- 4015077 TI - Risk factors of ventricular fibrillation during rapid amphotericin B infusion. AB - Amphotericin B causes reversible concentration-dependent loss of intracellular potassium in vitro and hyperkalemic ventricular arrhythmias in dogs. Hyperkalemic ventricular arrhythmias associated with amphotericin B infusion have not been well documented in humans. Ventricular fibrillation with progressive hyperkalemia (up to 8 to 8.4 meq/liter) occurred twice in an anuric patient during rapid infusion of high-dose amphotericin B (1.4 mg/kg over 45 min). The peak amphotericin B concentration in serum at the end of infusion was 6.7 micrograms/ml. Prolonged infusion (3 h) and concurrent hemodialysis each prevented the development of hyperkalemia and ventricular arrhythmia. In two anuric patients receiving 4-h infusions of amphotericin B during dialysis (0.7 and 1.0 mg/kg), peak amphotericin B concentrations in serum were lower, 1.6 +/- 0.1 and 2.7 +/- 0.7 micrograms/ml, respectively; serum potassium levels were maintained in the normal range; and venous access for outpatient therapy was convenient. Peak concentrations of amphotericin B in serum were also lower (1.7 +/- 0.7 micrograms/ml) in eight patients with normal renal function who received lower doses (0.7 +/- 0.2 mg/kg) over 45 min; there were only slight increases in the serum potassium level (from 3.9 +/- 0.9 to 4.4 +/- 0.6 meq/liter, P less than 0.05). We recommend that rapid infusion of amphotericin B not be used in patients with impaired potassium excretion unless accompanied by hemodialysis and careful potassium monitoring. PMID- 4015078 TI - Effects of general and local anesthesia on the pharmacokinetics of cefazolin in patients undergoing orthopedic surgery. AB - The pharmacokinetics of cefazolin in patients undergoing orthopedic surgery with either general (enflurane) or local (lidocaine or marcaine) anesthesia were studied. No differences in either mean serum levels at 30, 60, or 120 min after the intravenous injection of cefazolin or serum half-lives were seen between the two groups of patients. PMID- 4015079 TI - Prophylactic efficacy and tolerance of low-dose intranasal interferon-alpha 2 in natural respiratory viral infections. AB - The prophylactic activity of intranasal human interferon-alpha 2 (HuIFN-alpha 2) was determined in a randomized, double-blind, placebo-controlled study. Healthy, working adults self-administered sprays of HuIFN-alpha 2(1.25 X 10(6) IU; n = 142) or placebo (n = 145) twice daily. Drug administration was stopped after 12 days because of the frequent occurrence of nasal irritation manifested by blood tinged nasal mucus (44% HuIFN-alpha 2 versus 15% placebo, P less than 0.001) and associated nasal mucosal abnormalities. Over 80% of volunteers had participated in a similar field trial conducted 7 months earlier; no evidence of cumulative toxicity was detected. HuIFN-alpha 2 administration did not decrease the occurrence of illnesses associated with rhinorrhea, cough, or feverishness as compared to placebo, but the number of laboratory-documented respiratory viral infections was small (6 HuIFN-alpha 3 placebo). Intranasal HuIFN-alpha 2 1.25 X 10(6) IU twice daily was associated with significant local intolerance. PMID- 4015080 TI - Self-concept measurement in mentally retarded adults: a micro-analysis of response styles. AB - The Piers-Harris Self-Concept Scale and the Coopersmith Self-Esteem Inventory were administered orally to 46 mentally retarded adults employed in a sheltered workshop. In-depth analysis of transcripts of the taped testing sessions revealed that the majority of the item responses were ambiguous and not readily scorable within the standardized procedures. Characterization of the problematic response patterns indicated assorted qualifications, contradictory assertions, and responses which had little relevance to the item content. Of those factors that might account for these ambiguous responses, it appears that social desirability, acquiescence, personal agendas, recipient design errors, and lack of item comprehension are among the most salient. PMID- 4015081 TI - A comparison of the effects of interspersal and concurrent training sequences on acquisition, retention, and generalization of picture names. AB - A comparison was made between an interspersal and a concurrent procedure in teaching picture names to three mentally handicapped children. During the interspersal procedure a picture thats name was being trained was alternated with pictures already known; during the concurrent procedure a picture thats name was being trained was alternated with other pictures thats names were unknown. An ABA design with counterbalancing (BAB) was used. The children learned naming responses more rapidly when trained by the interspersal procedure than by the concurrent procedure. Weekly retention tests on pictures learned to criterion during the week showed no consistent difference between the two procedures in percentage of learned picture names retained. Weekly generalization tests showed that picture names that were retained in both conditions tended to generalize equally to a different setting and tester, and to the objects depicted in the pictures. PMID- 4015082 TI - A program to increase manual signs with severely/profoundly mentally retarded students in natural environments. AB - A classroom teacher and 12 residential staff members were taught to increase the opportunities for manual sign use with three severely/profoundly mentally retarded students, to use those opportunities for asking the students to sign request, and, if necessary, to provide prompts. A multi-faceted package consisting of written instructions, modeling, video presentation, visual cueing, feedback, and group discussion was used in a multiple-baseline design across situations. During intervention, (a) the number of opportunities for sign use increased in both classroom situations but remained stable on the ward, (b) the number of signs made by the students in response to the question increased across each of the situations, and (c) the number of spontaneously emitted signs increased. PMID- 4015083 TI - City-wide survey of drug patterns among non-institutionalized mentally retarded persons. AB - This was a survey of 1,012 non-institutionalized mentally retarded persons living in a medium-sized metropolitan area. The sample was drawn from special schools and two service agencies in Auckland that serve preschool and adult retarded people. These are the main organizations serving this population in Auckland, and collectively they include a large proportion of non-institutionalized retarded individuals in this city. A comprehensive summary of current medication was obtained for each subject. A variety of demographic, medical, social, and sleep data were collected and, where appropriate, information was gathered regarding time elapsed since the last seizure. Two percent of preschoolers, 3% of special school students, and 14% of adults were receiving psychotropic drugs. Anticonvulsant drugs were prescribed for 31% of preschoolers, 17% of special school cases, and 18% of the adults. A large proportion of the demographic, medical, and social/sleep variables were associated with drug prescription patterns. These factors were discussed with respect to other surveys, and possible explanations were offered to account for their relationship to pharmacotherapy. PMID- 4015084 TI - Training professionals to record proceedings of interdisciplinary team conferences. AB - Two experiments were conducted to assess the effectiveness of an instructional program in preparing staff and trainees at a university affiliated facility (UAF) to record proceedings of interdisciplinary team conferences. Training consisted of a self-instructional manual supplemented by a narrated videotape of a typical interdisciplinary case conference. Data were collected on the extent to which trainees correctly completed individual educational plan work sheets based on conference proceedings as a function of training. Findings of both experiments showed that the training program resulted in rapid acquisition of skills required to record team proceedings. PMID- 4015085 TI - Inhibition by antimicrobial food additives of ochratoxin A production by Aspergillus sulphureus and Penicillium viridicatum. AB - The effects of antimicrobial food additives on growth and ochratoxin A production by Aspergillus sulphureus NRRL 4077 and Penicillium viridicatum NRRL 3711 were investigated. At pH 4.5, growth and toxin production by both A. sulphureus and P. viridicatum were completely inhibited by 0.02% potassium sorbate, 0.067% methyl paraben, 0.0667% methyl paraben, and 0.2% sodium propionate. At pH 5.5, 0.134% potassium sorbate and 0.067% methyl paraben completely inhibited growth and ochratoxin A production by both fungi. Sodium bisulfite at 0.1%, the maximum level tested, was found to inhibit growth of A. sulphureus and P. viridicatum by 45 and 89%, respectively. Toxin production was inhibited by 97 and 99%, respectively. Sodium propionate (0.64%) at pH 5.5 inhibited growth of A. sulphureus and P. viridicatum by 76 and 90%, respectively. Toxin production was inhibited by greater than 99% for each fungus. Antimicrobial agents were ranked as to effectiveness by comparing the level required for complete inhibition of ochratoxin A production to the highest antimicrobial agent level normally used in food. At pH 4.5, the most effective inhibitor of growth and toxin production was potassium sorbate, followed by sodium propionate, methyl paraben, and sodium bisulfite, respectively, for both fungi. However, at pH 5.5, the most effective antimicrobial agents for inhibiting ochratoxin production were methyl paraben and potassium sorbate, followed by sodium propionate. Sodium bisulfite was not highly inhibitory to these toxigenic fungi at the higher pH value tested. PMID- 4015086 TI - Laboratory infection of chicken eggs with Campylobacter jejuni by using temperature or pressure differentials. AB - Fertile chicken eggs were infected in our laboratory with Campylobacter jejuni suspensions by using temperature or pressure differential methods of inoculation. After 2 days of incubation, over 90% of the eggs carried C. jejuni when iron was present in the inoculum. This percentage declined rapidly until by day 8, less than 10% of the eggs were detectably infected. However, up to 11% of hatched, healthy chicks carried C. jejuni in their intestinal tracts. The isolated organisms were of the same serotype as the initial inoculum. C. jejuni was recovered without difficulty when the intestinal tracts of chicks were enriched, but recovery from early dead-in-shell or infertile eggs was poor. This poor recovery and the rapid decline of C. jejuni after 2 days of egg incubation suggest that the vibrio is sensitive to some part of the incubating egg or to the temperature of prolonged incubation. It was impossible to predict which eggs would yield infected chicks on the basis of the number of organisms taken up by each egg, and no correlation existed between the number of organisms taken up and the efficiency of the hatch, i.e., the hatch ratio. If iron was omitted from the inoculum broth, the egg infection rate at day 2 was lower. PMID- 4015087 TI - Toxic effects of chlorinated and brominated alkanoic acids on Pseudomonas putida PP3: selection at high frequencies of mutations in genes encoding dehalogenases. AB - Mutant strains of Pseudomonas putida PP3 capable of utilizing monochloroacetate (MCA) and dichloroacetate (DCA) as the sole sources of carbon and energy were isolated from chemostat cultures. The mutants differed from the parent strain in that they could grow on products of MCA and DCA dehalogenation (catalyzed by inducible dehalogenases I and II) and were resistant to growth inhibition by the two substrates. The growth inhibition of strain PP3 by MCA, DCA, and other halogenated alkanoic acids was studied. Sensitivity to dehalogenase substrates was related to the expression of the dehalogenase genes. For example, mutants producing elevated levels of one or both of the dehalogenases were sensitive to 2 monochloropropionate and 2-monochlorobutanoate at concentrations which did not affect the growth of strain PP3. P. putida PP1, the parent of strain PP3, was resistant to the inhibitory effects of MCA and DCA. Spontaneous mutants of strain PP3, also resistant to MCA and DCA, were selected at high frequency, and four different classes of these strains were distinguished on the basis of dehalogenase phenotype. All dehalogenase-producing mutants were inducible; no constitutive mutant has yet been isolated. Most of the resistant mutants examined did not produce one or both of the dehalogenase, and over half of those tested failed to revert back to the parental (strain PP3) phenotype, indicating that the observed mutations involved high-frequency deletion of DNA base sequences affecting expression of genes encoding dehalogenases and associated permease(s). PMID- 4015088 TI - Serotyping of Campylobacter jejuni, Campylobacter coli, and Campylobacter laridis from domestic and wild animals. AB - By using 50 unabsorbed antisera, we were able to serotype 272 (65.7%) of 414 thermotolerant campylobacters from wild and domestic animals, on the basis of heat-stable antigens identified by means of passive hemagglutination. Forty-two serotypes were recognized. The pattern of serotypes detected in the various animal species was compared to human clinical isolates by using the Czekanowski index (proportional similarity index). The highest degree of similarity to the clinical isolates was observed for the poultry isolates, followed by strains from wild birds, flies, and pigs (in order of decreasing similarity). The serotypes recovered most frequently from poultry (LAU 1 and LAU 2) were also most prevalent in Norwegian patients. In contrast, serotype LAU 35/44, the predominant porcine serotype, was never recovered from human clinical specimens. Flies captured in chicken farms and in piggeries harbored serotypes which were also commonly seen in chickens and pigs, respectively. Nine of the strains included in this study could not be ascribed to any defined species. All of these were resistant to nalidixic acid and did not produce H2S. PMID- 4015089 TI - Tatlockia micdadei (Pittsburgh pneumonia agent) growth kinetics may explain its infrequent isolation from water and the low prevalence of Pittsburgh pneumonia. AB - Sediment and indigenous microflora taken from water distribution systems has been shown to promote the survival of Legionella pneumophila. The effect of sediment and indigenous microflora on Tatlockia micdadei (Pittsburgh pneumonia agent, PPA) was evaluated by growth curve experiments. Symbiosis between PPA and environmental bacteria was demonstrated by satellitism experiments. Unlike L. pneumophila, the concentration of PPA remained stationary in test tube suspensions containing both microflora and sediment. The difference in the ecology between the two organisms may explain the infrequent environmental recovery of PPA and, ultimately, the epidemiologic differences between Legionnaires disease and Pittsburgh pneumonia. PMID- 4015090 TI - Inhibition of mitogen-induced blastogenesis in human lymphocytes by T-2 toxin and its metabolites. AB - Concentrations of T-2, HT-2, 3'-OH T-2, 3'-OH HT-2, T-2 triol, and T-2 tetraol toxins which inhibited [3H]thymidine uptake in mitogen-stimulated human peripheral lymphocytes by 50% were 1.5, 3.5, 4.0, 50, 150, and 150 ng/ml, respectively. The results suggested that the initial hydrolysis of T-2 toxin and the hydroxylation of T-2 toxin to 3'-OH T-2 toxin did not significantly decrease the immunotoxicity of the parent molecule, whereas further hydrolysis to T-2 triol and T-2 tetraol toxins or hydroxylation to 3'-OH HT-2 toxin decreased in vitro toxicity for human lymphocytes. PMID- 4015091 TI - Growth of Legionella pneumophila in continuous culture. AB - A method was developed to grow Legionella pneumophila in continuous culture. A chemostat was used to simulate nutrient-limited, submaximal growth in the natural environmental and to provide a precisely controlled growth regimen. Cultures grew under forced aeration under conditions yielding up to 38% saturation of dissolved oxygen; supplemental CO2 (5%) at the same gas flow rates as ambient air had no effect on culture growth. Pleomorphism was observed during growth under all conditions. Pigment was produced only at D less than 0.03 h-1. Catalase was produced at higher growth rates but not at higher temperatures. The pathogenicity was unaffected by altering either the growth rate or the growth temperature. PMID- 4015092 TI - Substrate-induced changes in sulfhydryl reactivity of bacterial D-amino acid transaminase. AB - D-Amino acid transaminase from Bacillus sphaericus strain ATCC 14577 is a dimer with eight cysteinyl residues per molecule (T.S. Soper, W.M. Jones, and J.M. Manning (1979) J. Biol. Chem. 254, 10,901-10,905). The reaction of the cysteinyl residues with a variety of sulfhydryl reagents has been explored to gain insight into the physical environments around these cysteinyl residues in the absence or the presence of substrates. The native enzyme, in the pyridoxal-P conformation, appears to be a symmetrical dimer, whose SH groups react in pairs with anionic reagents such as 5,5'-dithiobis(2-nitrobenzoic acid) or the halo acids. Two SH groups react with either reagent without altering enzymatic activity. Two additional SH groups react with DTNB with loss of catalytic activity. Positively charged reagents such as beta-bromoethylamine are much more effective in inactivating the pyridoxal-P conformation of the enzyme with almost five of the eight SH groups reacting and this results in a significant loss in catalytic activity. The neutral reagent dithiodipyridine is able to detect some asymmetry in the pyridoxal-P conformation. Upon addition of a D-amino acid substrate, the enzyme is transformed into the pyridoxamine-P conformation. This conformation is much more reactive with anionic reagents and much less reactive with cationic reagents, suggesting that there is a significant change in the net charge around one of the SH groups in the pyridoxamine-P conformation. Also, titration with DTNB indicates that the enzyme is a much more asymmetric dimmer in the pyridoxamine-P conformation than in the pyridoxal-P conformation. Thus, upon binding of a D-amino acid substrate, D-amino acid transaminase is transformed into the pyridoxamine-P conformation. This results in a significant change in the environment of four of the sulfhydryl groups of the enzyme. We conclude that the enzyme is transformed from a symmetrical dimer into an asymmetrical dimer and that the net charge of one of the pairs of cysteinyl groups is changed from a net negative charge into a net positive charge. These results suggest that there is a significant conformational change that occurs during the transition from the pyridoxal-P into the pyridoxamine-P form of this transaminase. PMID- 4015093 TI - Conversion of alpha-amino acids and peptides to nitriles and aldehydes by bromoperoxidase. AB - Pure bromoperoxidase from the marine alga, Penicillus capitatus, converts alpha amino acids and peptides to the corresponding decarboxylated nitriles and aldehydes in the presence of hydrogen peroxide and bromide ion. Thus, both valine and valylvaline are converted to isobutyronitrile and isobutyraldehyde while alanine is converted to acetonitrile and acetaldehyde. The reaction is nonstereospecific and can be catalyzed by bromoperoxidases obtained from different sources. Bromoperoxidase catalyzes the conversion of methoxytyrosine to p-methoxyphenylacetonitrile. This reaction is consistent with the involvement of bromoperoxidase in the formation of aeroplysinin-1, a brominated aromatic nitrile antibiotic produced by a marine sponge. PMID- 4015094 TI - Influences of sulfated glycosaminoglycans on biosynthesis of hyaluronic acid in rabbit knee synovial membrane. AB - The effect of various sulfated glycosaminoglycans on glycoconjugates syntheses in synovial membranes of rabbit knee joints in culture was investigated by two different approaches. In the first approach, synovial membranes isolated from rabbit knee joints were cultured in the presence of sulfated glycosaminoglycans and [14C]glucosamine. In the second approach, solutions of sulfated glycosaminoglycans were injected into rabbit knee joints and synovial membranes isolated from the joints were cultured in the presence of [14C]glucosamine. The major part of [14C]glucosamine-labeled glycoconjugates associated with the synovial membranes and secreted into culture medium was hyaluronic acid. Of the natural glycosaminoglycans tested, dermatan sulfate gave the maximum stimulation of hyaluronic acid synthesis followed by chondroitin 4- and 6-sulfate. Heparin, heparan sulfate, keratan sulfate, keratan polysulfate, and hyaluronic acid had no significant effect. Of the chemically polysulfated glycosaminoglycans, GAGPS (a persulfated derivative of chondroitin sulfate) gave high stimulation but N acetylchitosan 3,6-disulfate had no effect. The effect of sulfated glycosaminoglycans on hyaluronic acid synthesis was the same in both experimental approaches. The increase in the amount of secreted hyaluronic acid in culture medium paralleled that in synovial membranes. The results indicate that the galactosamine-containing sulfated glycosaminoglycans have a specific stimulatory effect on hyaluronic acid synthesis. A high degree of sulfation of the molecules appeared to potentiate the stimulatory effect. PMID- 4015095 TI - Characterization and solubilization of an acyl chain elongation system in microsomes of leek epidermal cells. AB - Microsomes prepared from leek epidermal tissue readily elongate stearoyl-CoA to very long chain fatty acid with malonyl-CoA as the C2 unit. In the absence of stearoyl-CoA, but in the presence of ATP, microsomes elongate endogenous free fatty acids. Endogenous CoA is the source of CoA. Palmitoyl, stearoyl, and higher saturated acyl-CoAs are readily elongated by the microsomal system but oleoyl-CoA is ineffective; however, the higher monounsaturated acyl-CoAs can be elongated. Since the very long chain fatty acids of the leek epidermis are all saturated, it would appear that the reaction controlling the nature of the final acyl product is the inactivity of oleoyl-CoA as a substrate. There is no evidence that acyl carrier protein participates in the elongation reactions. Evidence is also presented suggesting that (a) there may be two elongation systems, one responsible for the conversion of stearoyl-CoA to arachidonyl-CoA and the second involved in the conversion of arachidonyl-CoA to very long chain fatty acids, and that (b) the elongation activities may be associated with a large polypeptide. PMID- 4015097 TI - Isolation and sequencing of an active-site peptide from spinach ferredoxin-NADP+ oxidoreductase after affinity labeling with periodate-oxidized NADP+. AB - Spinach ferredoxin-NADP+ oxidoreductase was inactivated by treatment with 2',3' dialdehyde NADP+ (periodate-oxidized NADP+), which selectively modifies a lysine residue at the nucleotide-binding domain of the enzyme. The identity of the derivatized residue was ascertained by thin-layer chromatography of the protein hydrolysate. Reductase that had been labeled with periodate-oxidized NADP+ and NaB3H4 was treated with trypsin, and samples of the tryptic digest were subjected to reverse-phase high-performance liquid chromatography. The radioactivity profiles showed modification of one specific peptide. The primary structure of this peptide was found to be Gly-Glu-Lys*-Met-Tyr-Ile-Gln-Thr-Arg, where Lys* represents the derivatized lysine. The sequence obtained corresponds to residues 242-250 in the primary structure of spinach ferredoxin-NADP+ reductase recently reported [Karplus et al. (1984) Biochemistry 23, 6576-6583]. PMID- 4015096 TI - Effect of selenium deficiency on the disposition of plasma glutathione. AB - Selenium deficiency causes increased hepatic synthesis and release of GSH into the blood. The purpose of this study was to examine the effect of selenium deficiency on the disposition of plasma glutathione. Plasma glutathione concentration was 40 +/- 3.4 nmol GSH equivalents/ml in selenium-deficient rats and 17 +/- 5.4 nmol GSH equivalents/ml in control rats. The half-life and systemic clearance of plasma glutathione were found to be the same in selenium deficient and control rats (t1/2 = 3.4 +/- 0.7 min). Because selenium-deficient plasma glutathione concentration was twice that of control, the determination that selenium deficiency did not affect glutathione plasma systemic clearance indicated that the flux of glutathione through the plasma was doubled by selenium deficiency. It has been proposed that the kidney is responsible for the removal of a major fraction of plasma glutathione. In these studies, renal clearance accounted for 24% of plasma systemic glutathione clearance in controls and 44% in selenium-deficient rats. This indicates that a significant amount of glutathione is metabolized at extrarenal sites, especially in control animals. More than half of the increased plasma glutathione produced in selenium deficiency was removed by the kidney. Thus, selenium deficiency results in a doubling of cysteine transport in the form of glutathione from the liver to the periphery as well as a doubling of plasma glutathione concentration. PMID- 4015098 TI - Isolation, amino acid sequence, synthesis, and biological activity of some oligopeptides from porcine spinal cord. AB - Four oligopeptides, designated SCP-3, SCP-4, SCP-5, and SCP-6, have been isolated and purified to homogeneity from porcine spinal cord. The amino acid sequences have been determined as pyroGlu-Gly, pyroGlu-Gly-Gly, Met-Met-Gly, and Asp-Ala Gly-Ala-Gly, respectively. All of these peptides have been synthesized by conventional liquid-phase or solid-phase methods. The synthetic and extracted peptides showed identical behavior in a reverse-phase high-performance liquid chromatography system. SCP-3 and SCP-4 exhibited some significant inhibitory activity on the electrical stimulation-induced contractions of longitudinal muscle strip of guinea pig ileum, and SCP-5 showed some stimulating effect on the same preparation. The physiological significance of these purified peptides is being investigated. PMID- 4015099 TI - Organization and structure of two mixed micellar phases of the sphingomyelin/Triton X-305 system. AB - Properties of mixed dispersions of sphingomyelin and the nonionic detergent, Triton X-305, were investigated by analytical ultracentrifugation and by autocorrelation spectroscopy of scattered laser light. These properties were compared with those of the sphingomyelin/Triton X-100 mixed micellar system reported previously [S. Yedgar, Y. Barenholz, and V. G. Cooper (1974) Biochim. Biophys. Acta 363, 98-111]. The substitution of the 30-unit ethylene oxide chain of Triton X-305 for the 10-unit chain of the Triton X-100 resulted in the appearance of two micellar phases at all detergent/lipid mixture ratios studied, whereas only a single mixed micellar phase was observed using Triton X-100. Despite this difference, the properties of the mixed lipid/detergent micelles obtained using Triton X-100 have been verified in the following respects: The detergent aggregation numbers in the mixed micelles are quite constant over a wide range of detergent molar fractions, being about 70 and 400 for the lighter and heavier mixed micellar phases, respectively. The detergent aggregation numbers are larger in the mixed micelle than in the pure detergent micelle. Very large sphingomyelin aggregation numbers can be accommodated within the mixed micelles, apparently by the critical intervention of the detergent molecules to produce a stable micellar structure. PMID- 4015100 TI - The mechanism of helical transition of proteins by organic solvents. AB - This paper describes a theory for the mechanism of three-state transition of proteins which is often observed in aqueous organic cosolvent systems, i.e., from the native, via intermediate to helical forms. The first transition, accompanied by changes in the tertiary and/or secondary structures, was explained by larger bindings of the organic solvent molecules to the intermediate than to the native state; the second transition, resulting in changes mainly in the secondary structure, i.e., helical transition, was explained by less hydration sites for the helical state. Computer simulations of the transition were carried out using plausible values for the number of alcohol and water binding sites of proteins as well as for the equilibrium constant of the transitions in the absence of cosolvent. A reasonable agreement with the experimental transitions was observed. The stronger effect of alcohols with longer alkyl chains was explained by their greater binding to nonpolar groups and their larger exclusion from peptide groups. PMID- 4015101 TI - Formation of benzo[a]pyrene-3,6-quinol mono- and diglucuronides in rat liver microsomes. AB - The formation of benzo[a]pyrene (BP)-3,6 quinol glucuronides in liver microsomes in the presence of UDP-glucuronic acid and NAD(P)H appears to occur by a sequence of three reactions: BP-3,6-quinone----BP-3,6 hydroquinone----BP-3,6-quinol monoglucuronide----BP-3,6-quinol diglucuronide. This conclusion is based on the following results. Incubations with [14C]BP-3,6-quinone or UDP-[14C]glucuronic acid and analysis of the samples by TLC established the existence and identity of the two BP-3,6-quinol glucuronides which exhibit different fluorescence spectra. The nature of the monoglucuronide, i.e., a quinol and not a semiquinone glucuronide, was suggested by the finding that the rate of diglucuronide formation was the same with or without NAD(P)H provided that a sufficient amount of monoglucuronide had been formed prior to oxidation of the nucleotides. Furthermore, BP-3,6-quinol monoglucuronides can serve as substrates in the formation of diglucuronides. The ratio between the decrease in monoglucuronides and the formation of diglucuronides was found to be close to 1, suggesting that the conversion of the monoglucuronide of BP-3,6-quinol to the diglucuronide is also catalyzed by UDP-glucuronosyltransferase. However, great differences in the pattern of induction of mono- and diglucuronide formation indicate that two different UDP-glucuronosyltransferases are involved. The yield of BP-3,6-quinol glucuronides with NADH relative to NADPH and the increase in glucuronide formation observed in the presence of cytosolic DT-diaphorase (NAD(P)H-quinone oxidoreductase) are discussed with regards as to whether DT-diaphorase plays an important role as a BP-3,6-quinone reductase in the formation of BP-3,6-quinol glucuronides compared to other NAD(P)H-oxidizing flavoproteins. PMID- 4015102 TI - Hydrogen-tritium exchange by apoferritin and ferritin. AB - The out-exchange kinetics of tritium from apoferritin, ferritin of various iron contents, and apoferritin subunits were examined. The exchange kinetics indicated no detectable conformational differences in the tetracosamer with and without hydrous ferric oxide in the internal cavity of the molecule. The data for apoferritin subunits were markedly different from those for the tetracosameric state. The exchange kinetics for apoferritin were consistent with a rapid exchange of water between the internal cavity of the protein and the bulk solvent outside the protein shell. PMID- 4015103 TI - The human erythrocyte ghost: a new experimental model for studying adenosine transport. AB - Previous work on adenosine transport has always had problems with the interference of adenosine metabolism, due to its high metabolic rate and because the enzymes involved are consistently present in most tissues. A new experimental model for studying adenosine transport in human erythrocyte ghosts is presented in this work: Human erythrocyte ghosts were sealed in the presence of erythro-3(2 hydroxynonyl)adenine and P1-P5-di(adenosine)5'-pentaphosphate, inhibitors of adenosine deaminase and adenosine kinase, respectively. These ghosts proved to lack adenosine metabolism when incubated in [U-14C]adenosine at 10 microM concentration at lack 37 degrees C for 60 min. Ghosts were 99.4% sealed in the correct orientation and had constant intracellular water volume. With these characteristics, the erythrocyte ghost preparation has many advantages for studying adenosine transport without adenosine metabolism interference. Adenosine transport was studied following the technique of W. R. Lieb and W. D. Stein [(1974) Biochim. Biophys. Acta 373, 165-177, 178-196.] Experiments to study Zero trans influx and efflux, equilibrium exchange, and infinite-trans influx and efflux are presented. Adenosine transport did not behave linearly in any of these experimental procedures. Adenosine basic kinetic constants, calculated according to the procedure of Lieb and Stein, were R1----2 = 4.1 X 10(-4), R2----1 = 3.97 X 10(-4), Ree = 1.94 X 10(-4), Roo = 6.08 X 10(-4), K1----2 = 125.67 microM, and K2 ---1 = 84.36 microM. Lieb and Stein rejection criteria were used to distinguish a simple pore from a simple carrier. The data accumulated indicate that adenosine transport is carried out by a system that satisfies the criteria used for the simple carrier model. Asymmetric behavior was observed indicating lower affinity of the carrier for adenosine influx, although Vmax values for influx and efflux were similar. PMID- 4015104 TI - Chalcone synthase from cell suspension cultures of Daucus carota L. AB - Chalcone synthase (CHS) has been partially purified about 35-fold. Withdrawal of 2-mercaptoethanol after precipitation with ammonium sulfate led to higher stability during further purification steps. In order to determine CHS activity, two procedures [according to Schroder et al. (1979) Plant Sci. Lett. 14, 281-286] were applied. The radioactivity extracted with ethyl acetate from the assay mixture (total products) was compared to 14C-labeled flavanone purified by TLC. The activity of CHS increased with bovine serum albumin (BSA) or 2 mercaptoethanol in the assay. Both effects were synergistic, but BSA did not promote "side products" as 2-mercaptoethanol did. BSA (10 mg ml-1) and 2 mercaptoethanol (1.4 mM) were components of the standard assay. Under these conditions, the CHS from Daucus carota had different pH optima for naringenin formation (7.9) and eriodictyol formation (6.8). The apparent Km values were 0.6 microM for 4-coumaroyl-CoA (pH 7.9), 7.7 microM for caffeoyl-CoA (pH 6.8), and 3.0 microM for malonyl-CoA (pH 7.9). Substrate inhibition was observed with 4 coumaroyl-CoA (greater than 10 microM) and malonyl-CoA (greater than 50 microM). The inhibitory activity of various flavonoids and related compounds (100 microM) was investigated. Naringenin and naringenin-chalcone inhibited eriodictyol formation totally and naringenin formation by 50%. In contrast, eriodictyol and eriodictyol-chalcone inhibited only eriodictyol formation by 40%. It was shown that the inhibition with naringenin was fully uncompetitive. These in vitro data support the view that the true substrate of CHS in D. carota is 4-coumaroyl-CoA. PMID- 4015105 TI - Heterogeneity of solubilized muscarinic cholinergic receptors: binding and hydrodynamic properties. AB - Previous studies have described the conversion, after detergent solubilization, of the multiple populations of membrane-bound muscarinic agonist binding sites to a population of uniform affinity. This paper describes the solubilization of at least two receptor species, distinct in their agonist binding characteristics, which are capable of interconversion by transition metal ions. This finding enabled a more detailed examination of the molecular properties and regional differences of brain muscarinic receptors than was previously possible. Muscarinic receptors (mAChR) obtained from the rat cerebral cortex or medulla pons were solubilized using digitonin or the zwitterion detergent, 3-[(3 cholamidopropyl)dimethylammonio]-1-propanesulfonate (Chaps). The equilibrium binding of the antagonist [3H]-4-N-methylpiperidyl benzilate ([3H]4NMPB) to detergent-solubilized receptors resembled binding to neural membranes and exhibited subnanomolar affinity, saturability, and simple mass action kinetics. Agonist binding to soluble preparations was measured by competition of [3H]4NMPB binding sites. Saturation isotherms for agonist binding to digitonin- and Chaps solubilized mAChR obtained from various brain regions appear flattened and have Hill coefficients in the range 0.52-0.78. Computerized modelling techniques indicate that the best fit to the experimental data is provided by a model specifying two soluble muscarinic agonist binding sites with differing dissociation constants, KH and KL, respectively. Solubilization of cerebral cortex membranes with Chaps or digitonin resulted in a population with a composition of high- and low-affinity sites similar to that found in the membrane bound state. In contrast, solubilization of the medulla pons resulted in an approximately 40% loss of high-affinity sites. Solubilized receptors retained the sensitivity to transition metals ions, but were insensitive to guanine nucleotides. Density gradient centrifugation indicated that Chaps-solubilized mAChR are composed of two molecular forms with S20,W equal to 9.9 S and 14.9 S. The 14.9 S species comprises approximately 30% of the total binding activity in the cortex and approximately 40% in the medulla. We identify the 14.9 S species as being associated with a guanylnucleotide binding protein because treatment of medulla membranes with guanylylimidodiphosphate prior to solubilization results in disappearance of 14.9 S with 9.9 S unchanged. Sedimentation of cortical mAChR in the presence of Cu+2 leads to an increase in 14.9 S to almost 50% of the total binding activity.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 4015106 TI - Sites of interaction of calmodulin with trifluoperazine and glucagon. AB - The combination of glucagon with calmodulin alters the microenvironment of Tyr 99, but not Tyr-138, and is blocked by the binding of trifluoperazine by calmodulin. Trp-25 of glucagon is probably involved in the zone of interaction, which may also overlap one or more strong binding sites for trifluoperazine. From energy transfer measurements, one strong binding site for trifluoperazine probably involves the N-terminal region of binding domain III. Energy transfer and other evidence suggest that the zone of contact with glucagon involves the N terminal region of binding domain III. PMID- 4015107 TI - Kinetics of kidney mitochondrial 25-hydroxycholecalciferol-1 alpha-hydroxylase in vitamin D-repleted weanling guinea pigs. AB - Kinetics of vitamin D-repleted guinea pig kidney mitochondrial 25 hydroxycholecalciferol-1 alpha-hydroxylase were studied. Omission of malate, source of mitochondrial reducing equivalents, abolished the 1 alpha-hydroxylase activity as well as the degradation of 1 alpha, 25-dihydroxycholecalciferol [1,25(OH)2D3], indicating that both functions shared elements of a common pathway. Preincubation of the mitochondrial preparation in presence of 10 nM 1,25(OH)2D3 for 15 min protected the labeled 1,25(OH)2D3 from degradation. Under these conditions an apparent Km of 605 nM and a Vmax of 40 pmol/30 min/mg mitochondrial protein were observed. These data show that this particular mammalian model may be used to study the modulation of mammalian 1 alpha hydroxylase activity. PMID- 4015108 TI - Determination of equilibrium constants for a sequential model of dioxygen binding by hemoglobin-inositol hexaphosphate complexes: the structural pathway from deoxy to oxy-hemoglobin. AB - The affinity of human hemoglobin (Hb4) for dioxygen was determined in 0.050 M bistris, 0.005 M inositol hexaphosphate (IHP) at pH 7.0 and 20.0 degrees C. Binding of dioxygen by Hb4 was determined by detailed spectroscopic analysis of the absorption spectrum in the region from 460 to 620 nm. The absorption spectrum of samples at intermediate values of fractional saturation (F) could not be resolved into components of Hb4 and (HbO2)4 without generating a residual spectrum, the amplitude of which was greatest at F from 0.4 to 0.5 and least at values of F of 0 and 1. An equation of state for dioxygen binding by the Hb4-IHP complex was formulated and tested by its ability to predict (i) the equilibrium binding curve and (ii) the variation in amplitude of the residual spectrum with F. The equilibrium binding data was fitted to the following equation of state: (Formula: see text) where K1 is the equilibrium constant for binding of dioxygen to an alpha chain of the Hb4-IHP complex, K2 is the constant for the second alpha chain, K3 is the equilibrium constant for the large-scale conformational change, K4 is the equilibrium constant for binding of oxygen by both beta chains, and (L) is the ligand concentration. The best-fitting values were as follows: K1, 0.03497 mm Hg-1; K2, 0.01368 mm Hg-1; K3, 2.44; K4, 0.0008867 mm Hg-2. The residual spectra were attributed to differential loading of dioxygen by the alpha and beta chains. Equations of state for F of each chain are presented, and the amplitude of the residual spectra was shown to be accurately predicted by the differences in F of each chain when subjected to the constraint that the best-fitting values of K1-K4 be used in predicting saturation of each chain with dioxygen. PMID- 4015109 TI - Biosynthesis of a chlorophyllide b-like pigment in phenanthroline-treated Chlamydomonas reinhardtii y-1. AB - Incubation of degreened Chlamydomonas reinhardtii y-1 cells in the dark with m phenanthroline induced de novo synthesis of a chlorophyllide b-like pigment. The rate of synthesis of this pigment in the dark was greater than that of total chlorophyll in illuminated cells. Most of the newly synthesized pigment was excreted into the culture medium. The product was extracted from the medium as the metal-free pheophorbide, which had a fluorescence excitation maximum at 428 +/- 1 nm and an emission maximum at 657 +/- 1 nm (E428F657) in ethyl acetate (E427F657 in diethyl ether). Three pheophorbide species were extracted from the medium of green cells treated in the dark, a minor component with a spectrum (E410F670) identical to demetallated chlorophyll a, and two major species with spectral values of E428F657 and E433F657. The latter, predominant form had a spectrum identical to demetallated chlorophyll b, which was purified from the algal cells. E428F657 and E433F657 reacted with hydroxylamine and Girard's T reagent, which caused a shift in the fluorescence emission maximum to 668 nm. Pheophytin b, which contains an aldehyde group, exhibited an identical spectral shift when treated in the same way, but pheophytin a or porphyrin biosynthetic intermediates did not. Proton NMR analysis of the E428F657 chlorin produced by yellow cells treated with m-phenanthroline confirmed the presence of an aldehydic proton. Chelating and nonchelating phenanthroline analogs equally stimulated synthesis of this product. PMID- 4015111 TI - Formation of single-stranded regions in the course of digestion of DNA with DNAase II and micrococcal nuclease. AB - In the course of digestion of DNA with DNAase II or micrococcal nuclease, considerable amounts of single-stranded (ss) regions are formed, as determined by a second digestion with ss-specific nucleases, hyperchromicity measurements, and electron microscopy. Most of the ss stretches are located internally in the DNA molecules. The effect appears to be related to regions of decreased stability arising around single-stranded cuts in the double helix. PMID- 4015110 TI - Decreased mitochondrial creatine kinase activity in dystrophic chicken breast muscle alters creatine-linked respiratory coupling. AB - Dystrophic chicken breast muscle mitochondria contain significantly less mitochondrial creatine kinase than normal breast muscle mitochondria. Breast muscle mitochondria from normal 16- to 40-day-old chickens contain approximately 80 units of mitochondrial creatine kinase per unit of succinate:INT (p iodonitrotetrazolium violet) reductase, a mitochondrial marker, while dystrophic chicken breast muscle mitochondria contain 36-44 units. Normal chicken heart muscle mitochondria contain about 10% of the mitochondrial creatine kinase per unit of succinate:INT reductase as normal breast muscle mitochondria. The levels in heart muscle mitochondria from dystrophic chickens are not affected significantly. Evidence is presented which shows that the reduced level of mitochondrial creatine kinase in dystrophic breast muscle mitochondria is responsible for an altered creatine linked respiration. First, both normal and dystrophic breast muscle mitochondria respire with the same state 3 and state 4 respiration. Second, the post-ADP state 4 rate of respiration of normal breast muscle mitochondria in the presence of 20 mM creatine continues at the state 3 rate. However, the state 4 rate of dystrophic breast muscle mitochondria and mitochondria from other muscle types with a low level of mitochondrial creatine kinase, such as heart muscle and 5-day-old chicken breast muscle, is slower than the state 3 rate. Third, dystrophic breast mitochondria synthesize ATP at the same rate as normal breast muscle mitochondria but rates of creatine phosphate synthesis in 20-50 mM Pi are reduced significantly. Finally, increasing concentrations of Pi displace mitochondrial creatine kinase from mitoplasts of normal and dystrophic breast muscle mitochondria with the same apparent KD, indicating that the outer surface of the inner mitochondrial membrane and the mitochondrial creatine kinase from dystrophic muscle are not altered. PMID- 4015112 TI - The effect of sexual hormones on the sulfated glycosaminoglycan pattern of male genital accessory organs. AB - The absolute and relative amounts of glycosaminoglycans and [35S]sulfate uptake were investigated in several tissues of male guinea pigs and rats under different sexual hormonal conditions (castration, estrogen treatment, or both). The hormonal effects, regarding the pattern of sulfated glycosaminoglycans, were specifically observed in the target organs (vas deferens and seminal vesicles) of both animals. Castration, in both species, decreases the amount of heparan sulfate and chondroitin sulfate, while diethylstilbestrol (DES) treatment causes different effects on rat and guinea pig target organs. In rats the effect of estrogen administration and surgical castration was essentially the same, and in guinea pigs DES increased the content of dermatan sulfate and chondroitin sulfate. The modifications in the specific patterns of the sulfated glycosaminoglycans suggest that these compounds are under sexual hormonal control only in the target organs, and show a specific pattern of distribution according to the tissue layer. PMID- 4015113 TI - Alterations in the physical state and composition of brush border membrane lipids of rat enterocytes during differentiation. AB - The physical state of the membrane lipid of brush border membranes, prepared from rat small intestinal villus and crypt cells, was examined by steady-state fluorescence polarization using three lipid-soluble fluorophors. Membranes prepared from crypt cells were found to possess a higher lipid fluidity than those of villus cells with each probe. Analysis of the composition of these membranes revealed that those from crypt cells had lower ratios of cholesterol/phospholipid (mol/mol), protein/lipid (w/w), and saturated fatty acyl chains/unsaturated chains (w/w). Alterations in the levels of stearic (18:0) and oleic (18:1) acids were responsible for differences in the latter ratio. The results, therefore, demonstrate that alterations in the lipid composition and fluidity of brush border membranes of enterocytes occur during the process of differentiation. PMID- 4015114 TI - The inhibition of plant mitochondrial respiration by the synthetic analog of ubiquinone, 5-n-undecyl-6-hydroxy-4,7-dioxobenzothiazole (UHDBT). AB - The quinone analog, 5-n-undecyl-6-hydroxy-4,7-dioxobenzothiazole (UHDBT), has been shown to inhibit cyanide-sensitive and cyanide-insensitive respiration in higher plant mitochondria. The inhibition is dependent upon the concentration of mitochondrial protein. The low concentrations of UHDBT required to inhibit the cyanide-sensitive pathway (microM) and the cyanide-insensitive pathway (nM) indicate that UHDBT is acting as a tight-binding inhibitor of ubiquinol oxidation. Inhibition of both pathways was dependent upon pH. It is shown that UHDBT appears to be a less potent inhibitor of cyanide-sensitive NADH oxidation than of cyanide-sensitive succinate oxidation, and that the pH dependence of inhibition of these two pathways differs. The inhibition of NADH and succinate oxidation by the cyanide-insensitive pathway shows similar pH dependences although at a given pH NADH oxidation is more susceptible to inhibition than succinate oxidation. PMID- 4015115 TI - [Diagnostic imagings of mediastinal mass]. AB - Conventional postero anterior and lateral chest radiographs constitute the first examination of the mediastinum. A well-penetrating radiograph of 130KV or more is needed to optimally, demonstrate the lung-mediastinal borders as well as air containing structures in the central thorax. Many mediastinal lesions that are obscure on conventional films are clearly demonstrated by CT, which clearly separates structures in the axial plane. The extent and localization of tumor can be more easily determined by CT than by other techniques. Conventional chest tomography has been popular in the past, but with the advent of CT scanning, this procedure has little in evaluating a mediastinal mass if CT is available. Nuclear scan using gallium 67 is fairly accurate in identifying inflammatory lesions and malignant tumors, but with the advent of CT such studies have little if any use in the mediastinum. The list of CT indications conforms somewhat to the report published by the Society of Computed Body Tomography, with some modifications. CT examination of the mediastinum has become one of the most useful complementary modalities in the diagnostic field and often not only is it complementary, but it may be an alternative to other X-ray studies, isotope scanning, or mediastinoscopy. PMID- 4015116 TI - [Treatment of mediastinal tumor]. AB - Mediastinal tumors show many kinds of histology. Surgery is indicated in almost all cases with the exception of malignant lymphomas. This review is divided into 3 parts, Surgical procedures: Some available approaches and special techniques for each tumor are described. Radiotherapy: thymoma, malignant lymphoma, neuroblastoma, and seminoma are indicated for radiotherapy. Chemotherapy: malignant lymphoma, neuroblastoma, germ cell tumors, and thymoma are indicated for chemotherapy. PMID- 4015117 TI - [Diagnosis and therapy of thymoma]. AB - In the postoperative diagnosis of thymoma, the most important problem over the last 30 years has been whether the condition is benign or malignant. In this paper, we discussed the diagnosis of thymoma malignancy and its therapy based on our own experiences. All thymomas have the potential to be malignant. Some thymomas have low malignancy and others high malignancy. As the malignancy is therefore not uniform, it is impossible to divide thymomas into either benign or malignant categories. Masaoka, one of the present authors, introduced the concept of clinical stage to thymoma. We think that the difference between invasive and noninvasive thymomas is due to differences in the clinical stage. We also proposed a new classification of thymomas based on the degree of epithelial differentiation. This new classification reflects the malignancy of the thymoma. Both the clinical stage classification and the classification based on epithelial differentiation showed good correlations with the prognosis of thymoma can be surmised by an exact diagnosis based on these two new classifications. The most important point concerning the therapy of thymoma is radical resection of the tumor. However, reduction surgery can be the method of second choice, especially in myasthenic thymoma, because of its slow growth. We carried out irradiation in all patients with thymoma postoperatively, resulting in a low rate of recurrence of the thymoma. This indicates the effectiveness of radiation therapy for this condition. PMID- 4015118 TI - [Classification and pathology of mediastinal tumors]. AB - The mediastinum is a longitudinal septum between the right and left pleural cavities which contains various organs and tissues. A variety of tumor and tumor like lesions develop in this region. There have been various disputes in the past regarding the histogenesis of thymomas, thymic carcinoids, germ cell tumors, and lymphocytic tumors, and these tumors and their associated disorders, including myasthenia gravis, have attracted the interest of surgeons, physicians, radiologists and pathologists. A general description of the classification and pathology of these interesting tumors has been given as an introduction to this special edition, "Diagnostics and Therapy of Mediastinal Tumors". PMID- 4015119 TI - [Shared antigens between BCG and tumor cells--immunotherapy with BCG for mouse tumor]. AB - Cytotoxic activity of anti-BCG rabbit serum (A-BCG) and the antigenic relationship between BCG and tumor cells were studies. A-BCG showed high cytotoxic activity against line 10 tumor cells of guinea pig Strain 2 and Colon 26 tumor cells of BALB/c mouse but not to cells of human bladder cancer (HT 1197, HT 1376). Cell-killing activity of A-BCG against line 10 and Colon 26 was dependent on complement participation. It was also found that Colon 26 cells were heterogenous in their susceptibility to the killing activity of A-BCG. Antigenic studies between BCG and tumor cells were undertaken using on indirect immunofluorescence method and it was found that all tumor cells used in the experiment shared common antigens with BCG. In immunotherapy with BCG for Colon 26 tumors, BCG worked effectively for suppressing tumor growth. However, enhancement of tumor growth in some of the BCG-treated mice was observed. PMID- 4015120 TI - [Phase II trial of mitoxantrone in patients with relapsed and refractory acute leukemia]. AB - Mitoxantrone, a new anthracenedione, was administered to twenty-five evaluable patients with relapsed or refractory acute leukemia between January 1982 and September 1984. Two patients were not evaluable because of early death. There were 18 males and 7 females with a median age of 42 yrs (range 6-70 yrs). Four of these were less than 14 yrs and 6 more than 55 yrs. The initial dose employed was 3 mg/m2/day X 5 days. Eventually a starting dose of 10 mg/m2 X 5 days was used. Among 16 patients with acute nonlymphocytic leukemia, there was one complete and 3 partial remissions. One of 4 patients with acute lymphocytic leukemia achieved a complete remission. Also, a complete remission was obtained in a patient with T cell lymphoma/leukemia. The overall remission rate was 24% with a complete remission rate of 12%. Remissions occurred at doses of more than 6 mg/m2/day X 5 days. Four of the 6 patients who had attained a remission received one of the anthracyclines. Bone marrow depression was the dose-limiting factor. Mucositis occurred in 6 patients to whom higher doses were administered. This mucositis was thought to be due to drug-related toxicity. The trials were too short to evaluate possible cardiac toxicity. These data indicate that mitoxantrone is a promising single drug for the treatment of relapsed or refractory acute leukemia. PMID- 4015121 TI - [Synergistic activation of rat alveolar macrophages by cepharanthine and OK-432]. AB - We studied the synergistic activation of rat alveolar macrophages (AM) by cepharanthine (Ceph.) and OK-432. Rat AM could be rendered much more tumoricidal against Walker-256 tumors in vitro after the i.v. injection of ceph. (5 mg/Kg) and OK-432 (5 KE/rat) thao of ceph. or OK-432 only. Radioactivity of 14C-acetate OK-432 trapped in murine lung after the i.v. injection of mixed of ceph. was much higher than of 14C-acetate-OK-432 only. Rat AM could be rendered tumoricidal by incubation in vitro with OK-432, but not with ceph. This finding suggests that if OK-432 is injected intravenously with mixed of with ceph., of OK-432 is trapped much more up by the lung without mixture, therefore AM can be much more tumoricidal. Intravenous administration of OK-432 with ceph. may be useful for reduction of lung metastasis by tumoricidal AM. PMID- 4015122 TI - [Phase II study of etoposide (VP-16) in the form of oral capsules for malignant lymphomas]. AB - Twenty-five patients with malignant lymphomas were treated with etoposide oral capsule 200mg/day for 5 days, repeated 3-4-weekly. Twenty-one cases were evaluable. CR was achieved in four cases (19.0%) and PR in six cases (28.6%). The most serious adverse effect of the drug was leukopenia. In one patient (6.7%) the leukocyte count was lower than 1,000/mm3. Gastrointestinal toxicities such as anorexia, nausea, vomiting and diarrhea occurred in about 66.7% of patients but were not serious; alopecia was observed in 65.2%. In conclusion, etoposide is considered effective for malignant lymphomas. PMID- 4015124 TI - Panniculitis in infants. PMID- 4015125 TI - Molluscum contagiosum and the acquired immunodeficiency syndrome. PMID- 4015123 TI - [Clinician-oriented and cytology-oriented autopsy, Part I. Respiratory system]. AB - The autopsy is performed with multiple purposes. It is felt that the first purpose of the autopsy is a service for clinicians. Dissection technic should be determined to present the best clinical pathological correlation of the lesions. Touch preparation (imprint) from the organs is most useful to establish initial pathological diagnoses during autopsy examination. This provides not only oncologic data (identification of tumors), but also the presence of infectious complications such as opportunistic organisms. Multiple photographs illustrate both the gross pathological lesions and infections, demonstrated by the imprints of the respiratory system. PMID- 4015126 TI - Histologic artifact due to Madajet. PMID- 4015127 TI - Eosinophilic cellulitis (Wells' syndrome) PMID- 4015128 TI - Estrogen and progesterone receptors are not increased in generalized essential telangiectasia. PMID- 4015129 TI - Cutaneous horn arising in chronic discoid lupus erythematosus. PMID- 4015130 TI - Conjunctivitis. PMID- 4015131 TI - Toxic epidermal necrolysis and amiodarone treatment. PMID- 4015132 TI - IgE antibodies to Staphylococcus aureus. Prevalence in patients with atopic dermatitis. AB - We determined the prevalence of IgE antibodies to Staphylococcus aureus by optimized immunoradiometric assay methods in serum specimens from 69 patients with atopic dermatitis. All patients had positive aerobic cultures for S aureus from skin. Significant binding attributable to IgE antibodies was noted in three of 25 patients with atopic dermatitis and superimposed impetiginization or pustules, but antibodies were not detected in the remaining 44 patients whose lesions were colonized with S aureus. By comparison, IgE antibodies to S aureus were uniformly present in high titer in serum samples from patients with the hyperimmunoglobulin E syndrome. We conclude that most patients with atopic dermatitis do not have detectable levels of IgE antibodies to S aureus. PMID- 4015133 TI - Etretinate therapy for psoriasis. Reduction of antibody-dependent cell-mediated cytotoxicity of polymorphonuclear leukocytes. AB - We monitored the antibody-dependent cell-mediated cytotoxicity of polymorphonuclear leukocytes from 14 patients with psoriasis before and during etretinate therapy. Neutrophils obtained from the patients with psoriasis at pretherapy demonstrated significantly greater cytotoxic activity than control cells. After four weeks of etretinate therapy, the cytotoxicity of neutrophils from the psoriatic patients decreased significantly and was no longer significantly different from the control value (at a 1:1 effector-to-target ratio). The decline in neutrophil cytotoxicity preceded significant clearing of our patients' psoriasis. The reduction in the antibody-dependent cell-mediated cytotoxicity of polymorphonuclear leukocytes from patients with psoriasis occurs early during therapy and may represent one of the mechanisms of action of etretinate. PMID- 4015134 TI - Familial multiple trichodiscomas. A clinicopathologic study. AB - Three patients had hereditary multiple trichodiscomas of early onset and dominant inheritance. This report is an analysis of the histologic, histochemical, immunohistochemical, and electron microscopic findings in 27 trichodiscomas, the largest published series so far, to our knowledge. The tumors of perifollicular connective tissue are briefly reviewed and a classification is proposed. Hereditary multiple trichodiscomas are regarded as a new entity that should be distinguished from the syndrome recently described by Birt and associates that is characterized by autosomal dominant inherited fibrofolliculomas as the hallmark, associated with trichodiscomas and acrochordons. PMID- 4015135 TI - Granuloma and pseudogranuloma of the skin due to Microsporum canis. Successful management with local injections of miconazole. AB - A 25-year-old immunosuppressed woman with systemic lupus erythematosus experienced a chronic cutaneous and subcutaneous infection due to Microsporum canis. The clinical course and response to therapy of this extremely rare form of dermatophytosis are described. PMID- 4015136 TI - Nocardia asteroides infection with dissemination to skin and joints. AB - A 56-year-old diabetic woman developed multiple cutaneous lesions and septic arthritis secondary to disseminated Nocardia asteroides pulmonary infection. The diagnosis was made rapidly by Gram's and acid-fast stains of pus, sputum, and synovial fluid and later confirmed by cultures. Sulfonamides are the drugs of choice for nocardiosis, and this patient had a complete response to two weeks of intravenous trimethoprim and sulfamethoxasole followed by three months of oral therapy. PMID- 4015137 TI - Cutaneous cryptococcosis resembling molluscum contagiosum in a patient with AIDS. AB - A 29-year-old Haitian man with the acquired immune deficiency syndrome (AIDS) developed disseminated cryptococcosis with an unusual cutaneous presentation. He had numerous hypopigmented papules over his face that clinically resembled molluscum contagiosum. To our knowledge, cutaneous cryptococcosis resembling molluscum contagiosum has not been previously reported. The patient had a T-cell defect consistent with AIDS and belonged to a high-risk group. To our knowledge, this is the second report of cutaneous cryptococcosis in a patient with AIDS. PMID- 4015138 TI - Cytophagic histiocytic panniculitis. Systemic histiocytosis presenting as chronic, nonhealing, ulcerative skin lesions. AB - Systemic histiocytosis was found in a patient who presented with chronic, nodular, and ulcerative skin lesions. The patient's hospital course was complicated by persistent fever, thrombocytopenia, severe neutropenia, and coagulation abnormalities. Treatment consisted only of splenectomy and supportive care. Postoperatively, the patient's skin lesions and the fever, pancytopenia, and coagulopathy resolved. Marked proliferation of histologically benign macrophages was observed in dermal, splenic, hepatic, and lymphoid tissues; leukophagocytosis and erythrophagocytosis were clearly demonstrated. This illness is most consistent with cytophagic histiocytic panniculitis, a newly described syndrome. PMID- 4015139 TI - Histoplasma panniculitis. AB - We encountered two cases of disseminated histoplasmosis with cutaneous involvement. The clinical and histopathologic findings were those of panniculitis. Primary pulmonary histoplasmosis typically induces a hypersensitivity panniculitis remote from the site of infection. In our cases of disseminated disease, however, the organisms were present in the skin and subcutaneous fat. PMID- 4015140 TI - Eosinophilic pustular folliculitis. Report of two cases with a review of the Japanese literature. AB - Two Japanese patients, a 29-year-old woman and a 21-year-old man, had typical eosinophilic pustular folliculitis characterized by pruritic, tiny, red, follicular papulopustules on the face and trunk and eosinophilia in the peripheral blood. The second patient also had palmoplantar pustular lesions. A review of the literature revealed that this folliculitis primarily affects the seborrheic areas and that in one fifth of the patients palmoplantar lesions are a concomitant finding. PMID- 4015141 TI - Eosinophilic pustular folliculitis (Ofuji's disease) with response to dapsone therapy. AB - A 50-year-old man had eosinophilic pustular folliculitis (Ofuji's disease) characterized by follicular pustular papules on the face, confluent vesicles on the fingers, and a papulopustular area on the upper portion of the back. Extensive examinations and cultures of both pustular material and tissue revealed no organisms, except Staphylococcus epidermidis. The disease responded to dapsone therapy. PMID- 4015142 TI - Facial burning and scarring in a child. PMID- 4015143 TI - Eliminating neonatal tetanus--an attainable goal. PMID- 4015145 TI - Selective surgical management of neural tube malformations. AB - The physical characteristics of 49 children with spina bifida cystica, survivors of a group subjected to selection for early surgery are compared with 39 children alive from an earlier unselected series, born in the 1960s, and reviewed retrospectively. Sixteen children were also studied in whom the initial decision not to operate had been followed by survival and subsequent treatment. Children selected for initial surgery have a significantly lower mortality than those not selected and their mobility at 5 to 7 years of age is better, although only marginally so compared with the unselected group. Selection does not decrease the need for shunt treatment of the associated hydrocephalus. None of those not initially selected for surgery have normal faecal or urinary continence, whereas 35% of the selected in group have normal continence and urinary tracts. Children treated immediately have significantly higher degrees of intelligence than both the unselectively treated and those whose treatment was delayed but a fifth of the latter group were intellectually normal. There were only small differences in intelligence between children given delayed treatment and those unselectively treated, suggesting that postponing surgery does not necessarily have a deleterious effect on ability. PMID- 4015144 TI - Congenital dislocation of the hip: early and late diagnosis and management compared. AB - During the decade 1970-9, 23 002 infants born in the University of Bristol Department of Obstetrics were examined for congenital dislocation of the hip by junior members of the paediatric staff on the first day of life and again on discharge from hospital. Suspected hip abnormality was checked by a senior member of the staff on the same day. A total of 445 (1.9%) infants were found to have a hip abnormality in the neonatal period. Immediate treatment in an abduction splint was undertaken, usually six weeks for dislocatable hips and 12 weeks for dislocated hips. Routine follow up included clinical and radiological examination at six, 12, 24, and 60 months. Altogether 90% completed the 12 month, 85% the 24 month, and 76% the 60 month checks. Five infants (1.1%) required further orthopaedic treatment (adductor tenotomy and abduction splinting) but no major surgery was necessary, nor was avascular necrosis encountered. The radiological results were excellent. Every effort (1970-84) was also made to identify all cases of late congenital dislocation of the hip diagnosed after the neonatal period in infants born to women in Avon during the same decade (n = 103 431). Ninety one cases were detected (0.88 per 1000 births), 10 in the university cohort (0.44 per 1000) and 81 in the non-university group (1.00 per 1000) (P less than 0.01). Seven of 10 in the former group required open surgery and in seven the radiological outcome at follow up was moderate or poor. The early and late diagnosed groups are compared in respect of perinatal factors and management. It is possible to detect most cases of congenital dislocation of the hip at birth and treat them safely and successfully. PMID- 4015146 TI - Long term prognosis of recurrent haematuria. AB - A long term follow up study of 100 children referred with recurrent haematuria for at least one year to two regional paediatric nephrology units is described. The mean duration of follow up was 8.2 years. An adequate renal biopsy was obtained in 96 and eight cases of Alport's syndrome and 10 of IgA nephropathy were diagnosed (20% and 26% respectively of the biopsies examined by electron microscopy and immunofluorescence). Five patients developed end stage renal failure and six hypertension requiring treatment, with the occurrence of these complications increasing progressively with increasing duration of follow up (1% at five years compared with 12% at 10 years). Adverse prognostic features were persistence of microscopic haematuria, proteinuria at presentation, and appreciable changes on renal biopsy. Eighty four patients had first degree relatives tested for haematuria; 30% of these families had another affected member. With long term follow up recurrent haematuria is associated with considerable morbidity and potential mortality. PMID- 4015147 TI - Familial juvenile nephronophthisis, Jeune's syndrome, and associated disorders. AB - Fourteen patients with familial juvenile nephronophthisis are described, eight of whom displayed one or more additional disorders. One boy with short limbed dwarfism and an abnormal chest was considered to have Jeune's syndrome; review of the published reports supports the view that nephronophthisis is the principal cause of renal failure in this disorder. Another patient with renal failure and retinitis pigmentosa at presentation developed progressive neurological and neuromuscular impairment leading to the discovery of ragged red fibre disease (mitochondrial cytopathy). Cardiomyopathy was present in this and one other patient. Tapeto-retinal degeneration, hepatic fibrosis, cerebellar ataxia, and oculomotor apraxia were among the other disorders encountered. Three patients presented in extremis with acute heart failure and irreversible oligo-anuria and this complication developed in another child who was already known to have nephronophthisis. Awareness of this disease and its associations is important for early diagnosis and appropriate management. PMID- 4015148 TI - Birthweight between 14 and 42 weeks' gestation. AB - Data representing fetal weight gain between 14 and 42 weeks' gestation are presented; firstly to provide suitable curves enabling the growth of the very immature infant to be monitored and secondly to examine the influence of the improved techniques of paediatric and obstetric assessment developed since the publication of previous studies. Data have been collected from the 57 866 livebirths in Sheffield between 1976 and 1984 and from therapeutically terminated and spontaneously aborted fetuses over the same period. It seems that preterm livebirths do not form a different population with respect to weight from the fetus still in utero, at least until the beginning of the third trimester. Previous studies have reported a bimodality of weight distribution in preterm infants at each gestational age which has been attributed to errors in gestational assessment. The pattern of distribution of weight in this study suggests that early ultrasonography and paediatric assessment techniques have exerted a considerable influence on the accuracy of gestational assessment. The mean weights of the sample differ considerably from those of the Gairdner and Pearson chart which are, therefore, considered to be inappropriate for the Sheffield population. PMID- 4015149 TI - Chronic non-specific diarrhoea. AB - Recurrent, unexplained diarrhoea is the most common intestinal complaint in children aged 6 months to 3 years. We studied 27 consecutive children with this complaint and followed them up until the age of 5 years. Diarrhoea began at the mean age of 9 months (range 4 to 16 months) and resolved in 21 children by 3 years of age. Twelve children had had infantile colic earlier. In six patients diarrhoea was caused by food allergy (cows' milk allergy and allergy to fresh vegetables). Episodes of diarrhoea persisted in four of these six. Twenty one children had unexplained diarrhoea: this resolved in 19. Nutritional deficiencies were rare; only one child had iron deficiency. Relative weights of the children were significantly lower at 2 years than at 1 year of age. At 5 years of age six of the children continued to have episodes of diarrhoea, and abdominal pains, headaches, and atopy occurred more commonly than in the general population. We suggest that there are two major subgroups among children with recurrent diarrhoea--children with food allergy and those who react to environmental stresses with a variety of somatic symptoms. PMID- 4015150 TI - Wheezing presenting in general practice. AB - General practice records of 1058 children were studied to determine the incidence, prevalence, natural history, diagnosis, and treatment of wheezing presenting in the first 21 years of life. Up to 7 years of age, boys were more likely to present with wheeze and to have recurrent episodes. Later there was a higher incidence in girls and a substantial rate of remission among boys, both contributing to changes in prevalence during later childhood and adolescence. All those diagnosed as asthmatic and two thirds of those with recurrent wheeze received bronchodilator treatment. PMID- 4015151 TI - BMX compared with ordinary bicycle accidents. AB - Three hundred new cases of bicycle accidents were seen in the accident and emergency department in 60 consecutive days. Fifty six per cent were related to ordinary cycles and 44% to BMX cycles. Significantly more children on BMX cycles were boys (94% v 76% on ordinary cycles). Those on BMX cycles were somewhat older and more had had previous accidents. By means of a proforma we investigated the nature and causes of the accidents, recorded the type of injury, and compared accidents on the two groups of bicycles. Forty children had fractures and the incidence on BMX machines was almost twice that on conventional bicycles as were serious injuries and admissions to hospital. Twenty one children had concussion, 18 broke teeth, 53 fell head first over handlebars, and 131 had injuries above the neck. Significantly more children on ordinary cycles (53%) had injuries above the neck than those on BMX cycles (31%). Difficulties and methods of preventing the increasing number of cycle accidents are discussed. PMID- 4015152 TI - Dress and care of infants in health and illness. AB - The mothers of 199 infants (mean age 36.7 days) were interviewed to determine how the infant was dressed and wrapped, and how the mother would deal with illness. These data were related to measures of the infant's toe and underarm temperatures and demographic information about the family. The data did not support the hypothesis that infants with particular types of clothing or bedding were at risk of overheating and shows that most mothers dress their infants appropriately. Mothers' ideas about management of illness were often inappropriate particularly in lower socioeducational groups. PMID- 4015153 TI - Pressure volume characteristics of the lungs in sudden infant death syndrome. AB - Data on the pressure volume characteristics of left lungs obtained from 23 babies dying from sudden infant death syndrome were compared with results from 18 length matched babies dying from established but primarily non-pulmonary causes. Volume distension at 30 cm of water and deflation flow volume characteristics were very similar in the two groups. These findings do not suggest that babies dying from sudden infant death syndrome have abnormally stiff lungs. PMID- 4015154 TI - Night cough counts and diary card scores in asthma. AB - A tape recording system for recording night cough in asthmatics at home is described. Objective cough counts and half hour periods containing cough did not correlate with diary card scores awarded to eight children on seven nights each. Night cough diary scores may mislead in the assessment of symptom severity. PMID- 4015155 TI - Remission of progressive renal failure in familial Mediterranean fever during colchicine treatment. AB - Colchicine was administered to a 12 year old girl with familial Mediterranean fever and progressive renal insufficiency. There was immediate resolution of abdominal attacks together with a dramatic fall in the serum creatinine concentration and the degree of proteinuria. At the same time her severely impaired growth was stimulated. PMID- 4015156 TI - Prognosis for babies born with fused eyelids. AB - The overall mortality for babies referred to our unit with fused eyelids was 68.7%; but when severe skin bruising was present only one of 18 babies survived (5.6%). This compares with a survival rate of 75% for those not bruised at or soon after birth. Skin bruising invariably indicates a very poor prognosis in babies born with fused eyelids. PMID- 4015157 TI - Unexpected cure in metastatic rhabdomyosarcoma. AB - A 3 year old boy presented with a presumably incurable form of rhabdomyosarcoma. Conventional treatment for advanced stage rhabdomyosarcoma (chemotherapy plus radiotherapy) was not used and intensive chemotherapy alone was given, resulting in an apparent cure. Our treatment rationale is discussed. PMID- 4015158 TI - Isolated myocarditis in the first year. AB - Over a period of nearly 40 years, 20 cases of isolated myocarditis were traced from 3086 necropsies. Seventeen occurred in infants less than 12 months of age, often with no antecedent clinical signs (sudden deaths) or with a short clinical history of less than 24 hours' duration. PMID- 4015159 TI - Management of school refusal. PMID- 4015160 TI - Changes in understanding of illness as the child grows. PMID- 4015161 TI - Diaphragmatic paralysis due to spinal muscular atrophy. PMID- 4015162 TI - Inspiratory: expiratory ratio and pulmonary interstitial emphysema. PMID- 4015163 TI - Apnoea monitors and sudden infant death. PMID- 4015164 TI - Who should get growth hormone? PMID- 4015165 TI - Complications of diazoxide in the treatment of nesidioblastosis. PMID- 4015166 TI - Infanticide, filicide, and cot death. PMID- 4015167 TI - Aetiology of idiopathic spinal deformities. PMID- 4015168 TI - Ischaemic spinal cord injury after cardiac surgery. AB - The case records of eight children with an acute spinal cord lesion after cardiac surgery were reviewed. All had been operated on for congenital heart disease over the past 10 years. The prognosis for neurological recovery was poor and scoliosis and bladder dysfunction were common complications. Ischaemic cord injury is usually associated with coarctation of the aorta but may occur when surgery is performed for other cardiovascular defects. PMID- 4015169 TI - Non-natural deaths in two health districts. AB - Details of all deaths in children (less than 16 years) resident in Oxfordshire and West Berkshire from 1970-9 were ascertained; 259 non-natural deaths were identified. Half were due to road traffic accidents, and another quarter occurred during play outside the home. There were differences in sex, age, and social class between the types of accident. A clustering of fatal accidents, particularly to pedestrians, was observed at around the time of the child's birthday. It is suggested that the excitement engendered overrides the child's normal caution. Local action to reduce accidents from specific hazards might complement national education campaigns. PMID- 4015170 TI - Sleep apnoea profile in preterm infants recovering from respiratory distress syndrome. AB - Polygraphic recordings were made on 10 preterm infants recovering from respiratory distress syndrome and 12 healthy preterm control infants at 40, 52, and 64 weeks' conceptual age to study the influence of respiratory distress syndrome on the development of the sleep apnoea profile. Two significant differences were found: infants with respiratory distress syndrome not only had a lower incidence of non-obstructive apnoea and periodic breathing at 40 weeks but also a persistently higher incidence of obstructive and mixed apnoea at 52 and 64 weeks' conceptual age; the latter finding being related to non-rapid eye movement sleep only. While the lower incidence of both types of apnoea at 40 weeks suggests an advanced maturation of respiratory drive, the persistence of obstructive and mixed apnoea related to non-rapid eye movement sleep may reflect the impact of respiratory distress syndrome on airway structures. PMID- 4015171 TI - Lack of association between barotrauma and air leak in hyaline membrane disease. AB - A retrospective analysis of 632 infants with hyaline membrane disease admitted to this regional intensive care nursery between 1 July 1974 and 31 December 1982 showed that 387 (61%) received mechanical ventilation. The ventilator pressures at the time the first air leak was detected were available from the records of 120 of 154 (78%) of the infants who sustained pulmonary air leak. There was a significant downward trend in both peak and end expiratory pressure used during the study period. The downward trend in peak pressure persisted when inborn and outborn infants, boys and girls, and infants more than 27, and 23 to 27 weeks' gestation were examined separately. Despite these trends there was no reduction in the incidence of pulmonary air leak in any group. These data do not support the hypothesis, implicit in the term barotrauma, that a reduction in ventilator pressures decreases the risk of air leak. PMID- 4015172 TI - Behavioural deviance and maternal depressive symptoms in paediatric outpatients. AB - A consecutive series of 95 3 to 4 year old and 43 7 to 11 year old children attending surgical, and medical outpatient clinics was studied, using questionnaires that measured behavioural deviance and had adequate reliability and validity for screening populations of children. A control group was also studied in the 7 to 11 year old sample. Depressive symptoms in the mothers of the children were determined using the Wakefield depression inventory. There was considerable behavioural deviance in children attending the outpatient clinics; 44% of the 7 to 11 year olds who were surgical outpatients had deviant scores. Thirty two per cent of mothers of medical outpatients had deviant scores on the depression inventory. These findings have relevance for the approach paediatricians take to their outpatients. PMID- 4015173 TI - Toxic shock syndrome. AB - Presenting features and clinical manifestations of six patients with toxic shock syndrome are reported. In four of the six cutaneous injury, sometimes trivial, occurred before the onset of symptoms and may have been a causal factor. All six children recovered. The need for early recognition and intensive management in this life threatening condition is discussed. PMID- 4015175 TI - Biotinidase deficiency: presymptomatic treatment. AB - Biotinidase deficiency presents with clinical signs of biotin deficiency at the age of 3 months, or soon after. In an infant in whom the diagnosis was made on cord blood, vision and hearing were normal before presymptomatic treatment with biotin. Physical and mental development are good at 14 months. PMID- 4015174 TI - The diabetic with a diabetic parent. AB - Six of eight children with diabetes who have a parent with type I diabetes mellitus presented serious management problems. The doctor and diabetic health visitor should be aware that these families may require extra support. PMID- 4015176 TI - Acid base balance in blood and cerebrospinal fluid. AB - Thirty four infants were studied; 21 with acute gastroenteritis, dehydration, and metabolic acidosis and 13 who served as controls. All infants with metabolic acidosis and without neurological signs had a normal to near normal cerebrospinal fluid acid base balance, but five with metabolic acidosis and severe neurological signs had cerebrospinal fluid acid base disequilibrium. Acute metabolic acidosis in infants may lead to cerebrospinal fluid acid base imbalance causing cerebral dysfunction. PMID- 4015177 TI - Hepatitis B virus replication in acute glomerulonephritis with chronic active hepatitis. AB - A 3 year old boy who had chronic active hepatitis type B with features of ongoing liver damage and active virus replication, developed acute membranous glomerulonephritis two years after the clinical onset of liver disease, when both hepatitis B e antigen and antibody were detectable in serum. After withdrawal of short term steroid treatment and resolution of hepatitis B virus replication, both glomerulonephritis and chronic hepatitis went into remission. Some months later hepatitis B surface antigen was no longer found in serum. PMID- 4015178 TI - Recurrent croup. AB - Thirty one of 486 children followed from birth had recurrent croup in the first four years of life. Twenty one were boys, and 10 girls. Recurrent croup occurred significantly more often in families with a positive history of allergy but was not significantly associated with the initial feeding method. PMID- 4015179 TI - Screening for congenital hypothyroidism: the first decade. PMID- 4015180 TI - Inaccurate coding corrupts medical information. PMID- 4015181 TI - Welfare of children in hospital. PMID- 4015182 TI - Activation of complement by 405-nm light in serum from porphyria cutanea tarda. AB - Sera from three patients with porphyria cutanea tarda (PCT) were examined for evidence of complement activation. The irradiation of sera in vitro with 405-nm light resulted in a dose-dependent diminution of total hemolytic complement activity and the hemolytic titers of C1, C4, C2, C3, and C5. Furthermore, such irradiated sera showed immunoelectrophoretical C3 conversion, chemotactic activity for rat polymorphonuclear leukocytes inhibited by incubation with anti C5 antisera but not anti-C3 antisera, and C5a generation as measured by radioimmunoassay. Factor-B conversion did not occur in such irradiated sera. Using Sephadex G-75 chromatography, the irradiated sera showed a multiphasic elution profile of chemotactic activity similar to that of zymosan-activated serum. The generation of C5a even occurred in factor-B-depleted serum. These studies indicate that the irradiation of PCT serum with 405-nm light induces the activation of the complement system via the classical pathway, resulting in the development of a chemotactic factor. PMID- 4015183 TI - Circadian rhythm of the in vivo migration of neutrophils in psoriatic patients. AB - Neutrophil chemotaxis in ten subjects with psoriasis was evaluated in vivo by the quantitative skin-window technique using autologous serum and in vitro using a modified Boyden technique. The in vitro chemotaxis values of the psoriatics were significantly lower (P less than 0.01) than those of healthy controls. When measured in vivo, however, we found that, after 9, 12, and 24 h, the values of the migrating polymorphonuclear leukocytes (PMNL) of psoriasis patients were only slightly and non-significantly lower than normal values. Analysing the in vivo chemotaxis data by a chronobiological method, we demonstrated statistically significant circadian rhythms in nine of the ten psoriasis patients. In seven of the patients, we found that the population had a significant rhythm, with the acrophase at -328 degrees. Our in vitro and in vivo values are in agreement with previously published values. However, there was a definite circadian rhythm of migration that we could not demonstrate in normal controls. We consider that our data reveal a significant and important difference between neutrophil chemotaxis in vivo in normal subjects and that in patients with psoriasis. PMID- 4015184 TI - Lymphocyte transformation to membrane-conjugated, liposome-conjugated, or unconjugated pentadecylcatechol in the guinea pig. AB - This study examined the in vitro immunogenicity of haptenated liposomes and compared them with haptenated biological membranes and unconjugated hapten. Peripheral-blood lymphocytes were obtained from guinea pigs topically sensitized with pentadecylcatechol (PDC) and immunologically naive guinea pigs. Lymphocyte transformations were studied by [3H]thymidine uptake. PDC failed to stimulate the lymphocytes from the immunologically naive group. There was significant blastogenesis in the cells of the sensitized group, but the degree of stimulation was dependent upon the manner in which the antigen was presented to them. Unconjugated hapten caused a low-level, dose-dependent mitogenesis in the sensitized T cells, and hapten-conjugated liposomes enhanced this response (P less than 0.05). By far the most effective immunogen was a haptenated biologic membrane. In all cases, the mitogenic response was macrophage dependent. It is possible that the haptenated biologic membranes were more effective than synthetic membranes (liposomes) because of the presence of membrane proteins that can conjugate with hapten and from a more effective immunogen. PMID- 4015186 TI - Percutaneous penetration of hair dyes. AB - Scalp penetration of 7 hair dyes (oxidative and direct) that occurs under conditions of hair dye usage was evaluated for both rhesus monkey and man using 14C labeled materials by quantifying their absorbtion via urine assays. Both species showed a remarkably similar pattern of dye penetration. The extent of scalp penetration is slightly higher for direct dyes but in neither case does it exceed 1% of the applied dose. PMID- 4015185 TI - The effect of estradiol on the sebaceous gland of the hamster ear and its antagonism by tamoxifen. AB - To evaluate the antagonism between estradiol and tamoxifen in the sebaceous gland of the hamster ear, animals were topically treated, and the size of the sebaceous glands was measured by histoplanimetry. The systemic effects were described by determining the estradiol and testosterone plasma levels and within the testes, and the size of the seminal vesicles and the contralateral sebaceous gland. The administration of 0.1 micrograms estradiol resulted in a diminution in the size of the treated glands but left all other parameters unchanged, indicating a purely local effect. A higher dose of estradiol (1 microgram) further decreased the size of the treated glands, but this was combined with a systemic effect, i.e. low plasma testosterone, decrease in testis size and a diminution of the contralateral ear gland. Ten micrograms of estradiol maximally suppressed all of the androgen effects without side effects. The administration of tamoxifen alone also decreased the size of the sebaceous glands without side effects, but it did not affect the production or effects of androgens. When administered in combination with estradiol, it antagonized the effects of this hormone completely. We conclude that tamoxifen inhibits the negative effect of estradiol on sebaceous-gland size. It acts predominantly in a systemic manner, because a metabolisation to monohydroxytamoxifen is necessary. PMID- 4015187 TI - Langerhans-cell degeneration in X-linked dominant ichthyosis. A quantitative and ultrastructural study. PMID- 4015188 TI - Quantitative analysis of eumelanin and pheomelanin in human malignant-melanoma tissues. PMID- 4015189 TI - The outcome of pregnancy and preterm delivery after conization of the cervix. AB - Of 607 women who had undergone conization of the cervix in 1973-1980 in the country of Funen, Denmark, 128 women had completed a total of 166 pregnancies before April 1, 1982. There was apparently no adverse effect of conization on these pregnancies. The frequency of delivery before 37 completed weeks of gestation, of a birthweight less than 2500 g or below the 10th percentile did not differ from that for a population standardized for age and parity. Five women had a second trimester abortion in a pregnancy after conization, but without evidence of cervical insufficiency. Eleven conized women had a caesarean section in a subsequent pregnancy for reasons unrelated to conization. PMID- 4015190 TI - Increased lysosomal fragility in the human uterine cervix following estrogen therapy. AB - In vitro stability of the lysosomal membrane complex was studied in non-pregnant human uterine cervices. The oestrogen therapy caused markedly enhanced lability of the lysosomal membrane complex as evidenced by higher activity of the "marker" enzyme when the preparations were challenged by mechanical or detergent stress. Oestradiol-17 beta might be implicated in altering the metabolism of the proteoglycan complex which may result in the "ripening" of the pregnant cervix. PMID- 4015191 TI - The value of ovarian and placental steroid determinations in abnormal early pregnancy. AB - Concentrations of estradiol (E2), progesterone (P), and 170H-progesterone (170H P) were measured by radioimmunoassay in serum samples obtained from a group of 98 women with threatened (n = 60), incomplete (n = 22) or missed (n = 16) abortion between the 4th and 17th week of pregnancy. The diagnosis was based on the clinical symptoms and the results of ultrasound scanning. In threatened abortion 54, out of 60 E2 values were within the 95% normal range, including most of the cases in which abortion occurred later. In incomplete abortion 18 of 21 E2 values were below the lower 95% confidence limit. In missed abortion, 11 of 15 E2 values were abnormal, being below the 95% normal range. Similar patterns in women with threatened, incomplete or missed abortion can be observed for values of P and 170H-P. Our results indicate that serum determinations of ovarian and placental steroids in women with early pregnancy failure are not of great clinical value. PMID- 4015193 TI - [Clinical pharmacology in geriatrics]. PMID- 4015192 TI - Plasma angiotensin I and serum placental leucine aminopeptidase (P-LAP) in pre eclampsia. AB - A study was undertaken on serial measurements of plasma angiotensin I (A-I) and serum placental leucine aminopeptidase (P-LAP) activities in normal and pre eclamptic pregnancy. There was the significant difference in A-I levels between normal and mild pre-eclamptic pregnancy at weeks 30, 35, 37, between normal and severe pre-eclamptic pregnancy at week 37. There were no differences in serum P LAP between normal and mild pre-eclamptic pregnancy up to week 33, but thereafter the levels for the mild pre-eclampsia were significantly higher than for the normal pregnancy. The P-LAP activity for the severe pre-eclampsia reached its maximum level at week 31. Around this week, the levels for severe pre-eclampsia were significantly higher than in the normal pregnancy. After week 35, the activities decreased precipitously to week 40; the activities for severe pre eclampsia in late pregnancy at weeks 39 and 40 were significantly lower than in normal pregnancy. The above data support the idea that P-LAP test is useful for prediction or diagnosis of pre-eclampsia. PMID- 4015194 TI - [Effect of stable strontium on spontaneous and drug-induced motor activity in the rat]. PMID- 4015195 TI - Action of aluminum chloride in isolated muscular strips of rat stomach fundus. PMID- 4015196 TI - [Effect of cortisol administration on the fate of nitrogen in malnourished pregnant rats]. PMID- 4015197 TI - N-acetyl-L-cysteine in acute cobalt poisoning. PMID- 4015198 TI - [Effect of oils heated with aniline on development in the Wistar rat]. PMID- 4015199 TI - Routine quantification of rheumatoid factor by rate nephelometry. AB - In a cross-sectional study of over 3000 consecutive serum specimens the levels of rheumatoid factor (RF) measured by rate nephelometry (Beckman ICS II) were compared with values obtained by the more traditional methods of sheep cell agglutination (Rose-Waaler) and latex agglutination. Similar values for sensitivity and specificity were found for all three methods for rheumatoid arthritis, with nephelometry giving slightly higher levels of sensitivity for other rheumatic disorders. A significant correlation (r = 0.46, p less than 0.01) was found between the nephelometric and Rose-Waaler method for 147 consecutive seropositive specimens. Of interest, however, several disparate results were observed, and explanations for these were sought. Longitudinal studies of RF were performed in 49 seropositive patients over a two-year period. The nephelometric method was considered superior compared with the other techniques because of its ability to detect changes in absolute levels at earlier stages and its low interassay coefficient of variance (11%). We conclude that the nephelometric technique appears suitable for routine diagnostic use, offers several advantages compared with more traditional methods, and is no more expensive per test specimen than the Rose-Waaler technique. PMID- 4015200 TI - Studies on the interaction of rheumatoid factor with monosodium urate crystals and case report of coexistent tophaceous gout and rheumatoid arthritis. AB - Gout and classical rheumatoid arthritis rarely coexist. We report a patient with strong evidence for both these diseases. Possible reasons for the negative correlation between these diseases are summarised. One hypothesis suggests inhibition of surface activity of monosodium urate crystals (MSU) by binding of rheumatoid factor (RF). This was studied with a purified monoclonal rheumatoid factor (mRF) with specificity for IgG. The mRF bound preferentially to MSU coated with IgG in contrast with the IgM control. Inhibition of the neutrophil chemiluminescence (CL) response to IgG-coated MSU was observed at concentrations of mRF that had no effect on the CL response to uncoated crystals. Neutrophil activation was not altered by coating crystals with an IgM control at the same concentration. These data suggest that RF may bind to antigenic determinants on exposed Fc of adsorbed IgG and block the interaction of crystal-bound IgG with Fc receptors. Although crystal coating by RF may modify the expression of gouty arthritis, it is unlikely to be the sole explanation for the dissociation between gout and RA. PMID- 4015201 TI - Demonstration of an abnormality of C apoprotein of very low density lipoprotein in patients with gout. AB - The very low density (VLDL) apolipoproteins of 12 male patients with gout have been studied by analytical isoelectric focusing. The relative percentage distribution of the C apolipoproteins was calculated and compared with that from 12 normolipidaemic and 12 'lipid-matched' controls. In the gout patients apolipoprotein CII (apo CII) represented 19.6% of the VLDL C proteins and the CII/CIII2 ratio was 0.57. In the normolipidaemic controls apo CII represented 28.8% and in the lipid-matched controls 33.1% of VLDL apo C, and the CII/CIII2 ratio approached one in each control group. These differences were significant. This suggests that a reduction in VLDL apo CII may predispose to the hypertriglyceridaemia that is commonly found in patients with gout. PMID- 4015202 TI - Plasma or serum from patients with systemic sclerosis alters behaviour of normal erythrocytes. AB - Incubation of washed normal erythrocytes with fresh or frozen plasma or serum from patients with systemic sclerosis (SS) significantly decreased the filterability of the cells, whereas the incubation of homologous normal serum or plasma with washed erythrocytes did not alter the filterability of these cells. The endothelial cell adherence of normal erythrocytes was increased by 3.5- and 2.6-fold (p less than 0.01) respectively when plasma or serum from patients with SS rather than that from normal controls was added to the incubation medium. Further investigation and isolation of the reactive material(s) present in the serum and plasma of patients with SS, which affect the deformability and endothelial cell adherence of erythrocytes, may be helpful in understanding the pathogenesis of the disease. PMID- 4015203 TI - Acute autonomic neuropathy in association with systemic lupus erythematosus. AB - A patient is described with acute autonomic neuropathy, developing post partum in association with systemic lupus erythematosus, and showing a rapid clinical response to steroids. The pattern of tissue damage is suggestive of an immunologically mediated mechanism. PMID- 4015204 TI - Complete heart block and bowel infarction secondary to rheumatoid disease. AB - A case of complete heart block secondary to rheumatoid involvement of the conduction system is presented. The same patient died after infarction of the colon as a consequence of arterial spasm superimposed upon pre-existing rheumatoid changes in the mesenteric arteries. The coexistence of rheumatoid involvement of the heart and of the bowel vasculature has not previously been reported. PMID- 4015205 TI - Extracellular fluid deficit following operation and its correction with Ringer's lactate. A reassessment. AB - The changes in extracellular fluid volume (ECV) in two groups of surgical patients, one receiving Ringer's lactate solution intraoperatively and the other receiving only dextrose and water, were assessed. A deficit in the ECV, as measured by radioactive sulfate, of 1.9 +/- 0.8 l (p less than 0.003) compared to the preoperative volume was found in the dextrose group. This was accompanied by a decrease in the mean creatinine clearance (-13% p less than 0.01), the mean urinary sodium excretion (-57% p less than 0.05), and the mean rate of clearance of the sulfate tracer (-18% p less than 0.01). The use of intraoperative Ringer's lactate (1660 cc +/- 96 cc) resulted in no change in the ECV, an increase in the mean creatinine clearance (+10% p less than 0.05), and no change in sodium excretion or tracer clearance. As a result of these findings, it appears that postoperative sodium retention is a physiologic response to a decreased ECV, which can be prevented by the administration of Ringer's lactate. PMID- 4015206 TI - Serum-mediated depression of neutrophil chemiluminescence following blunt trauma. AB - To investigate one possible mechanism responsible for decreased neutrophil bactericidal activity following trauma, the chemiluminescence response of normal neutrophils was measured following incubation in nonseptic and septic serum from 19 blunt trauma patients. Incubation of normal neutrophils in septic patients' sera (61 studies) resulted in a marked decrease in the chemiluminescence response (36 +/- 26% of control), compared to incubation in nonseptic sera (92 studies, 80 +/- 53% of control; p less than 0.005). This difference between nonseptic and septic serum was apparent immediately after injury, prior to the development of sepsis (47 +/- 4% versus 77 +/- 12%; p less than 0.05). The depression of the CL response was due to a suppressive factor present in septic patients' sera. This factor was nondialyzable and was present in high performance liquid chromatography (HPLC) fractions containing protein of molecular weight 50 to 100,000. Removal of albumin using Affigel-blue did not remove the suppressive factor. In contrast to the suppressive effect of septic trauma serum, septic patients' neutrophils had a normal chemiluminescence response after their isolation and washing. We conclude that trauma results in the generation of a serum factor that suppresses neutrophil chemiluminescence and that is present in greater amounts in patients who eventually become septic. This factor may be responsible for the decreased bactericidal activity and depressed host defense following injury. PMID- 4015207 TI - Use of transcutaneous oxygen tension measurements [PtcO2] in the diagnosis of peripheral vascular insufficiency. PMID- 4015208 TI - Bacteriology and septic complications of patients with appendicitis. PMID- 4015209 TI - Lumpectomy and level 1 axillary dissection prior to irradiation for operable breast cancer. PMID- 4015210 TI - Recurrent carotid stenosis. A five-year series of 65 reoperations. AB - From 1979 to 1983, 1726 carotid endarterectomies were performed at the Cleveland Clinic. During this period, 39 men (mean age, 60 years) and 22 women (mean age, 63 years) required 65 reoperations (3.8%) for correction of recurrent carotid stenosis occurring 3 to 194 months (mean, 42 months) after previous endarterectomy at this center (N = 43) or elsewhere (N = 22). Remedial procedures were necessary because of restenosis demonstrated by routine noninvasive testing in 32 asymptomatic lesions and because of neurologic symptoms in 33 others. The mean recurrence interval was 57 postoperative months for atherosclerosis (N = 37) in comparison to 21 months (p = 0.0007) for myointimal hyperplasia (N = 28), and was 48 months for men in comparison to 31 months for women (p = NS). Hypercholesterolemia appeared to be associated with late atherosclerotic recurrence (p = 0.05), but was not a feature of myointimal hyperplasia. Patch angioplasty (N = 59) or graft replacement (N = 3) was employed during 62 of the 65 reoperations, with a total of two operative deaths (3.1%), one nonfatal stroke (1.5%), and six transient cranial nerve injuries (9.2%). Three unrelated late deaths have occurred within a mean follow-up period of 23 months, but only three patients have experienced subsequent neurologic symptoms. PMID- 4015211 TI - Endothelial preservation in reversed and in situ autogenous vein grafts. A quantitative experimental study. AB - The hypothesis that superior endothelial preservation occurs when in situ (as opposed to harvested and reversed) autogenous veins are used as arterial grafts was investigated in a canine model by quantitating endothelial loss as seen on scanning electron micrographs. In situ grafts were compared to atraumatically dissected, nondistended, reversed grafts and to grafts distended to 500 mmHg pressure. Two hours after arterial transplantation, endothelial denudation averaged 3.9 +/- 6.7% on in situ grafts, 18.6 +/- 5.9% on reversed grafts (p less than 0.01), and 35.3 +/- 5.4% on reversed and distended grafts (p less than 0.001). At 24 hours after grafting, a significant increase (p less than 0.01) in endothelial destruction on in situ grafts resulted in a smaller, yet still significant difference in endothelial preservation between in situ and reversed grafts (15.2 +/- 9.5% vs. 25.1 +/- 23.4%, p less than 0.05). Endothelial healing was largely accomplished at 2 weeks regardless of technique. No difference in endothelial fibrinolytic activity could be detected between in situ and gently handled, reversed grafts at 24 hours or 6 weeks after surgery. An obligatory, although modest, degree of endothelial destruction occurred on the undissected portion of in situ grafts as a consequence of exposure to arterial hemodynamics. However, in the immediate postoperative period, endothelial preservation on in situ grafts surpassed that seen in even the most gently handled reversed vein grafts. PMID- 4015212 TI - The natural history of diagnosed gallstone disease in symptomatic and asymptomatic patients. AB - The natural history of gallstone disease in 691 patients, followed for a mean +/- SD duration of 78 +/- 61.6 months (median 62.9 months), is presented. These patients are all subscribers of a large health maintenance organization and are believed to represent a cross-section of middle income Americans. Symptoms attributed to biliary tract disease were present in 556 (80.5%), and the other 135 (19.5%) patients were asymptomatic. In the symptomatic group, the mean +/- SD duration of observation was 82.9 +/- 63.2 months (median 68.5 months); 242 (44%) eventually underwent biliary tract operations most often because of persistent symptoms. Only 10% of asymptomatic patients followed for 58 +/- 50.2 months (median 46.3 months) developed symptoms of biliary calculi, and seven per cent required operations. There were 50 deaths in this series of 691 patients, 25 in the symptomatic group, and 25 in the asymptomatic. Only two of these deaths were biliary tract related, and both were in the symptomatic group. This study suggests that patients with silent stones do not need to be operated on prior to the development of symptoms. In addition, many patients with symptoms of biliary calculi can tolerate their symptoms for long periods of time and prefer this course of action to cholecystectomy. PMID- 4015213 TI - Predictive ability of choledocholithiasis indicators. A prospective evaluation. AB - To assess the predictive ability of various indicators of common bile duct calculi, 457 patients undergoing cholecystectomy for gallstone disease were prospectively screened for the presence of 11 predefined criteria of possible choledocholithiasis. The predictive ability of the criteria, individually and in combinations, was determined. For all criteria, except a history of pancreatitis, a significantly increased incidence of choledocholithiasis was found. The number of positive criteria correlated positively with the frequency of common bile duct calculi. The negative predictive value and sensitivity of the total set of criteria were 98% and 89.5%, respectively. Following common duct exploration, the number of complications and the duration of postoperative hospitalization were significantly increased as compared with simple cholecystectomy. Peroperative cholangiography with cholecystectomy is recommended in all patients, with one or more criteria of possible choledocholithiasis. Routine peroperative cholangiography in patients with no positive criteria does not seem to be necessary. PMID- 4015214 TI - Experimental evidence for a vagally mediated and cholecystokinin-independent enteropancreatic reflex. AB - Truncal vagotomy results in diminished pancreatic protein secretion in response to intraduodenal fat. This diminished secretion may be due, at least in part, to interruption of the vagal reflexes between the intestine and the pancreas that work independently of cholecystokinin (CCK). In five dogs with chronic pancreatic fistulas, plasma CCK concentrations and pancreatic protein secretion in response to an intestinal stimulant (intraduodenal oleate) and to two exogenous peptides (bombesin and CCK-33) were compared before and after bilateral truncal vagotomy. Vagotomy decreased integrated protein secretion by about 50% in response to intraduodenal oleate. In contrast, protein output in response to parenteral stimuli increased after vagotomy. Integrated output of CCK in response to intraduodenal oleate or to exogenous bombesin or CCK was not significantly affected by vagotomy, but release of pancreatic polypeptide was decreased significantly in response to all stimuli after truncal vagotomy. These data provide evidence that truncal vagotomy decreases pancreatic protein secretion in response to intestinal stimulants by interrupting enteropancreatic reflexes mediated by the vagus, while maintaining normal (or supranormal) sensitivity of the pancreas to endogenous and exogenous CCK. PMID- 4015215 TI - Volvulus of the colon. Incidence and mortality. AB - Between 1960 and 1980, 137 patients with colonic volvulus (52% cecal, 3% transverse colon, 2% splenic flexure, and 43% sigmoid) were seen at the Mayo Clinic. Among the 59 patients with sigmoid volvulus, four (7%) had colonic infarction. Total mortality with sigmoid volvulus was seven per cent. There were 71 patients with cecal volvulus. Colonoscopic decompression was accomplished in two of these patients; in 15 (21%), gangrenous colon developed and mortality was 33%. Total mortality for cecal volvulus patients was 17%. Mortality for all forms of volvulus in patients with viable colons was 11%. Mortality for all patients with volvulus was 14%. PMID- 4015216 TI - Time and type of prophylactic surgery for familial adenomatosis coli. AB - Data on 61 kinds of familial adenomatosis coli registered in Finland, including 185 affected members, were collected to evaluate the chronological evolution of carcinoma in this disease. The long-term results for 52 patients undergoing colectomy and ileorectostomy were reviewed. Colorectal carcinoma occurred in 105 patients, with cumulative percentages of 1, 6, 16, 28, and 42 at 20, 25, 30, 35, and 40 years of age. Only three out of 50 call-up patients (6%) had a carcinoma, as compared with 62% in the propositi group. No cases of rectal stump carcinomas were recorded after 52 ileorectostomies in a follow-up period of up to 21 years (mean 6 +/- 5 S.D. years). It was concluded that prophylactic colectomy must usually be performed at 20 to 25 years of age, at the latest. Despite conflicting earlier evidence, colectomy and ileorectal anastomosis may still be a viable alternative, providing that the rectal stump is very short (5 to 10 cm) and the surveillance and treatment of all new adenomas is effective. PMID- 4015217 TI - Thin level IV malignant melanoma. A subset in which level is the major prognostic indicator. AB - A small proportion of "thin" malignant melanomas will metastasize and cause death. To assess the role of discordance between the major indicators of tumor depth (thickness and level) as a possible explanation for this phenomenon, prognosis by level has been examined in 255 cases, with tumors ranging in thickness from 0.6 to 1.1 mm. This is the range of thickness at which levels II, III, and IV overlap. The 5-year survival rate of patients with level IV tumors in this thickness range (59.35%) was poor (p less than 0.0001), relative to that of patients with level II (96.8%) and III (94.49%) lesions in the same range of tumor thickness. The distributions of other major prognostic indicators, among the groups of patients with tumors at each level, were examined to assess the possible contribution of factors other than level to the differences in survival between the three groups. These differences in survival could not be attributed to differing distributions of tumor thickness, tumor location, or patient sex. Of six prognostic variables, examined by Cox multivariate regression analysis, for tumors of thickness 0.6 to 1.1 mm, only level was found to have independent prognostic significance (p = 0.0025). The thin level IV melanoma appears to be an important exception to the rule that this melanomas are associated with an excellent prognosis. In this, as well as in other studies, after accounting for the effect on prognosis of tumor thickness, level has been shown to be a prognostic indicator with independent significance. The continued use of level as a prognostic indicator, in addition to thickness, is recommended. PMID- 4015218 TI - Endorectal ileal pullthrough with isoperistaltic ileal reservoir for colitis and polyposis. AB - Seventy-eight patients with ulcerative colitis refractory to medical therapy and eight with colonic polypisis have undergone total colectomy mucosal proctectomy, endorectal ileal pull-through with ileoanal anastomosis, and diverting ileostomy at the UCLA Medical Center during the past 7 years. Seventy-seven patients underwent a second stage operation with construction of a lateral isoperistaltic ileal reservoir, 12 to 30 cm long, and closure of the ileostomy. A reservoir 10 to 15 cm long appears optimal for children, and one 20 cm long appears to function best for adults. Major complications were either related to obstruction of the reservoir outlet from leaving a rectal muscle cuff longer than 6 cm, and/or constructing the reservoir too long in the early experience (16 patients), or from cuff abscesses (four patients). Out of the 77 patients, these problems led to reservoir removal in three, temporary ileostomy in eight, and reservoir revision in 16. Persistent cuff abscess was the cause for reservoir removal in two of four patients. Continence was achieved in all patients within 2 weeks. Good to excellent results were obtained in 65 patients. At one year, 78% were completely continent during the day, 18% had minor seepage, and four per cent had occasional soiling. Frequency of defecation in patients without complications, or those surgically corrected, was seven per 24 hours within 3 months. There were no deaths. Six patients were found to have unsuspected cancer at operation. No patient experienced bladder dysfunction or abnormal sexual function. Although a technically difficult operation, the long-term results indicate that the pullthrough operation is a good alternative to proctocolectomy with ileostomy. PMID- 4015219 TI - Penetrating duodenal injuries. Analysis of 100 consecutive cases. AB - One hundred consecutive patients with penetrating duodenal injuries were reviewed retrospectively to analyze the results of various methods of treatment. The severity of the abdominal injury was quantified by the Penetrating Abdominal Trauma Index (PATI). The overall mortality was 25%. Sixteen per cent of the deaths were related to extensive associated organ injury, eight per cent to sepsis, and one per cent to concurrent head trauma. Duodenal fistulas occurred in four per cent and were associated with mortality in two per cent. The complications of duodenal fistula, abdominal sepsis, and mortality from sepsis were significantly higher in those patients treated by repair and decompressive enterostomy with or without a serosal patch than in those with repair or resection. The severity of duodenal and associated organ injuries, as well as the clinical status, were similar in both groups. It is concluded that the majority of duodenal injuries from penetrating trauma may be treated effectively by primary repair, and that the use of decompressive enterostomy or serosal patch appears to contribute to an increased morbidity rate. PMID- 4015220 TI - A new type of sliding hiatus hernia. AB - A series of patients showing a previously unrecognized type of sliding hiatus hernia is presented and analyzed. This type of hernia is characterized by reflux of the mucous membrane of the Hiss angle into the lumen of the esophagus. The occurrence of mucosal prolapse is a secondary phase of gastroesophageal reflux. The mucous plug prevents further reflux of the acid contents of the stomach into the esophagus and mouth. After the appearance of mucosal prolapse, the symptoms and signs of esophagitis disappear. The most characteristic complaint of the patients is retrosternal pain on lying and bending down. Endoscopy with provocative tests reveals the mucosal prolapse. Tooth erosions due to previous acid reflux into the mouth are diagnostic. The symptoms of this new subtype of sliding hiatus hernia were cured by the Nissen fundoplication. PMID- 4015221 TI - Is there an association between failed antireflux procedures and delayed gastric emptying? AB - Recurrence of gastroesophageal reflux symptoms following antireflux surgery is a difficult clinical problem. Sixteen patients (6 men, 10 women; median age 59; range 33-75 years) with a positive endoscopy or pH-probe-assessed acid reflux and recurrence of reflux symptoms following a fundoplication underwent radionuclide solid and liquid gastric emptying studies. The median time between operation and gastric emptying study was 39 months (range 13-89 months). A control group of 21 patients (10 men, 11 women; median age 47; range 19-72 years) who had undergone a standard fundoplication was similarly studied 6 months following surgery. The per cent of solid remaining at 100 minutes in the stomach had a median value of 43% (range 5-89) in the control group. This was significantly less (p less than 0.0001) than in the failed operative group (median 66%, range 27-100). Similarly, the time taken for 50% of the liquid to leave the stomach had a median value of 13 minutes (range 8-27) in the control group; a value significantly less (p less than 0.01) than the failed operative group (median 18.5 min, range 2-60). It is not known whether the delayed emptying in the failed operative group is responsible for the failure of the antireflux surgery. However, delay in gastric emptying either before or after surgery may be of value in predicting patients likely to have poor outcomes. PMID- 4015223 TI - The relation between carcinoma of the gallbladder and an anomalous connection between the choledochus and the pancreatic duct. AB - An anomalous connection between the choledochus and the pancreatic duct may be associated etiologically or pathogenetically with congenital biliary dilation and carcinoma of the dilated bile duct. During the past 10 years, a total of 14 cases of carcinoma of the gallbladder with an anomalous connection between the choledochus and the pancreatic duct were encountered. These cases were studied in reference to their clinical features and histological findings. An experimental model of pancreatic juice inflow into the gallbladder of mongrel dogs was produced and the histological changes of the mucosa of that organ was observed. The intent was to elucidate the relationship between carcinoma of the gallbladder and this anomaly. The results of this clinical and experimental study suggest that reflux and stasis of pancreatic juice in the gallbladder induce chronic cholecystitis with intestinal metaplasia. This may be important in the pathogenesis of well-differentiated carcinoma of the gallbladder. PMID- 4015222 TI - Abdominal CT scanning in critically ill surgical patients. AB - Clinical parameters, intensive care unit (ICU) course, abdominal computed tomography (CT) scans, and the clinical decisions of 53 critically ill patients were reviewed to determine the influence of the CT scan. No scans were positive before the eighth day. Sensitivity was 48% and specificity, 64%. Seventeen (23%) scans of the 72 provided beneficial results: eight localized abscesses that were drained; nine were negative and not operated on. Five (7%) scans provided detrimental information: scan negative with abscess discovered or scan positive but negative laparotomy. Fifty (70%) scans were either of no help or not used in management. The mortality rate was 50% when CT led to an intervention, and 47% in the entire group. Hospital charges were +33,408. Personnel time and cost were 497 hours and +3658; of the total +37,066, 77% (+28,541) could be considered wasted. From these data, it was concluded that CT scans should be used to confirm abscesses, not to search for a source of sepsis. PMID- 4015224 TI - Hepatic resection for metastatic colon and rectal cancer. An evaluation of preoperative and postoperative factors. AB - Hepatic resection for metastatic colorectal cancer has been reported in over 700 patients. However, approximately 5000 patients each year are candidates for surgical excision. Since 1972, 25 patients have undergone hepatic resection for colorectal metastases at New York University. Potentially curable synchronous lesions were detected by preoperative liver chemistries and operative palpation. Patients were screened for metachronous lesions by serial liver chemistries and carcinoembryonic antigen (CEA) determinations; when clinical findings or laboratory findings were either positive or equivocal, then scanning techniques were used. Most patients had solitary lesions (20). Thirteen of 25 lesions were synchronous; 12 were metachronous. Anatomic lobectomy was performed in 13 patients (6 extended resections); and wedge resection was performed in 12. The operative mortality rate was four per cent; the 2-year survival rate, 65%; the 5 year survival rate, 25%. Hypertonic dextrose solutions were administered during and after operation. Post-operative albumin requirements ranged from 200 to 300 grams/day. Coagulation factors II, V, VII, and fibrinogen decreased after surgery to 30 to 50% of their preoperative levels. Subsequent elevation of these factors correlated with increased bile production and improvement in liver chemistries 10 to 14 days after operation. At present, hepatic resection for colorectal metastases provides the only potential method of salvage, offering a 20 to 25% long-term survival rate. PMID- 4015225 TI - Oophorectomy and colon cancer. Impact on survival. AB - Data on survival and survival free-from-recurrence were analyzed retrospectively in a group of 571 women who had undergone curative resection for colon cancer at the Mayo Clinic between 1972 and 1978. Of these women, 75 (group 1) had required bilateral oophorectomy before or at colon resection, while 496 (group 2) retained one or both ovaries. Average age, location and grade of tumor, and duration of follow-up were similar for both groups. Five-year-survival rate for the 571 women was 73.6%, as compared with 84.3% for matched controls. The 5-year survival rates were not significantly different for group 1 (78.0%) and group 2 (72.9%). Five year survival free-from-recurrence also was not significantly different (82.9%, group 1 and 79.5%, group 2). Women in group 1 who had grade 1 or 2 tumors or lesions in the sigmoid and cecum fared the best (no significant difference from controls). Incidence studies of ovarian metastases from colon cancers suggest that three to eight per cent of women should benefit from bilateral oophorectomy. This agrees with the difference in survival observed between groups 1 and 2 in this study. Our sample size is too small to statistically confirm the reliability of this difference. The design of a prospective study testing this hypothesis is outlined. PMID- 4015226 TI - Preoperative radiation therapy for clinically resectable adenocarcinoma of the rectum. AB - This is an analysis of 71 patients with clinically resectable adenocarcinoma of the rectum treated with preoperative irradiation and surgery at the University of Florida from July 1975 through December 1981. Seven patients were found to have liver metastasis at surgery; six had a complete resection of their primary rectal lesion and one had an incomplete resection of the rectal tumor. The remaining 64 patients had no evidence of metastasis at the time of surgery and underwent a complete resection of their rectal cancer. In the early years of the trial, the maximum tumor dose consisted of 3000 to 3500 rad in 3.5 to 4 weeks; the dose was subsequently increased to 4500 rad in 5 weeks. Patients were taken to surgery between 2 and 11 weeks (mean, 3.5 weeks) following the completion of radiation therapy. All patients have a minimum follow-up of 3 years and 63% have a minimum follow-up of 5 years. The acute complications of treatment have been acceptable, with only one patient requiring a treatment rest for moist desquamation of the perineum. All patients completed the irradiation course and all were operated on. Pathologic examination of the surgical specimen revealed no tumor in 11%, and the incidence of positive lymph nodes was 19%, which was half the incidence of positive lymph nodes in a series of historical controls treated from 1959 to 1976 with surgery alone. Comparison of patients treated with preoperative irradiation and surgery with those treated with surgery alone revealed that the postoperative complications have been similar in incidence, distribution, and severity. There have been no postoperative deaths. The overall incidence of local-regional recurrence is 5/64 (7.8%), and the combined incidence of local-regional recurrence and/or distant metastasis is 18/64 (28%). The incidence of local regional recurrence by preoperative dose is 3/23 (13%) for doses of 3000 to 3500 rad and 2/41 (5%) for doses of 4000 to 5000 rad. The 5-year local-regional failure rate is 3/40 (7.5%) for the group irradiated before surgery, and 39/135 (29%) for the historical controls managed by surgery alone (significance level = 0.015). The 5-year determinate disease-free survival is 27/38 (71%) for the patients irradiated before surgery, and 47/114 (41%) for the historical group of patients treated with surgery alone (significance level = 0.008). PMID- 4015227 TI - Hormonal role of adenosine in maintaining patency of the ductus arteriosus in fetal lambs. AB - The hypothesis that endogenously released adenosine plays an important role in maintaining patency of the fetal lamb ductus arteriosus was tested. The design of the study was (1) to determine the effect, if any, of exogenous adenosine on blood flow through the ductus arteriosus and (2) to evaluate the relationship among the partial pressure of oxygen in arterial blood, circulating endogenous plasma adenosine concentration, and the rate of blood flow through the ductus. When exogenous adenosine (5 mumoles) was administered during oxygen-induced ductal constriction, ductal blood flow increased from 101 +/- 6 ml/min to 153 +/- 4 ml/min (p less than 0.01). When fetal blood adenosine concentrations were measured during nonventilation and ventilation with 100% oxygen, endogenous adenosine concentrations fell to less than one-half of the preventilation levels, i.e., from 1.12 +/- 0.17 to 0.49 +/- 0.03 microM (p less than 0.01). Finally, when fetal lambs were ventilated with increasing concentrations of oxygen (0%, 10%, 20%, 60%, and 100%) and measurements obtained simultaneously at each level, there was a significant monoexponential relationship among the rise in PO2, the fall in plasma adenosine concentration, and the decrease in ductal blood flow. These data suggest that: (1) adenosine is a potent vasodilator of the lamb ductus arteriosus during oxygen-induced vasoconstriction; (2) fetal endogenous plasma adenosine levels fall significantly when PO2 is increased; and (3) the fall in adenosine concentrations parallels a decrease in ductal blood flow. The findings suggest that the endogenous vasodilator adenosine plays an important role in maintaining ductal patency in utero. PMID- 4015228 TI - Sequential changes in circulating total protein and albumin masses after abdominal vascular surgery. AB - Sequential changes in total circulating protein (TCP) and total circulating albumin (TCA) masses after different blood replacement regimens were investigated in a prospective study involving 40 patients undergoing reconstructive abdominal aortic surgery. Group I (13 patients) had 80 gm of albumin during operation and 60 gm of albumin during the following 3 days. Blood loss was replaced milliliter for milliliter by whole blood. Group II (14 patients) had the same blood substitution but no albumin. In group III (13 patients), 800 ml of blood loss was replaced by salt water. Maximum decrease in TCP (group II: 17%, group III: 29%) was found 4 hours after the operation. On postoperative day 1, protein mobilization to plasma equalling 10% of TCP had occurred. On day 4, TCP and plasma colloid osmotic pressure had not changed in group I, indicating an unchanged TCA/TCP ratio. In groups II and III, a significant decrease in TCP was followed by complete recovery of TCP. This also entailed a decrease in the TCA/TCP ratio, indicating an enhanced synthesis of acute-phase proteins. Based on these findings, a depression of globulin synthesis by supplemental albumin administration is proposed. PMID- 4015229 TI - Vascular access for hemodialysis. Patency rates and results of revision. AB - Over a 4-year interval, 324 arteriovenous conduits were created in 256 patients with end-stage renal disease as access for chronic hemodialysis. These included 154 Cimino fistulae, 163 polytetrafluoroethylene (PTFE) grafts, and seven miscellaneous grafts. Satisfactory patency rates were demonstrated for as long as 4 years for both Cimino fistulae and PTFE grafts by life-table analysis. Failures of Cimino fistulae usually occurred early in the postoperative period, secondary to attempts to use inadequate veins. Thrombosis caused the majority of PTFE graft failures and was generally the result of venous stenosis. Correction of such venous stenosis is mandatory to restore graft patency and can result in prolonged graft survival. PMID- 4015230 TI - Lung vascular injury with protease infusion. Relationship to plasma fibronectin. AB - Fibronectin exists in a soluble form in plasma and in an insoluble form in tissues. Plasma fibronectin can modulate phagocytic function as well as incorporate into the tissue matrix where it is believed to influence microvascular integrity and tissue repair. The temporal alterations in plasma and lung lymph fibronectin were studied in relation to increased pulmonary vascular permeability induced by protease infusion. The acute sheep lung lymph fistula model was used. A 39% decrease in plasma fibronectin (control = 421 +/- 67 micrograms/ml) was observed 2.5 hours (255 +/- 43 micrograms/ml) after protease infusion. There was an elevation of lymph fibronectin early after protease infusion, followed by a progressive decline. Concomitant with the decrease in plasma fibronectin, an increase in lymph flow (QL) of greater than 200% (from a control of 6.7 +/- 1.0 ml/hr to 13.9 +/- 1.4 ml/hr) was observed within 2.5 hours. Also, there was a sustained elevation in the total protein lymph/plasma concentration (L/P) ratio, which was maximal at 2.5 hours. The transvascular protein clearance (TVPC = QL X L/P) was 4.5 +/- 0.7 ml/hr at the control period and 13.1 +/- 2.0 ml/hr by 2.5 hours. This was indicative of increased flux of protein-rich fluid across the pulmonary endothelial barrier. Lung vascular permeability stabilized after 2.5 hours as manifested by a slowly declining L/P ratio. Thus, plasma fibronectin deficiency may contribute to the etiology of increased lung vascular permeability with protease infusion. Since the progressive decline in plasma fibronectin was not reflected in a proportional increase in lymph fibronectin, plasma fibronectin may have sequestered in tissues such as the lung, or perhaps in reticuloendothelial cells during the injury phase. Whether the progressive decrease in plasma fibronectin reflects its incorporation into the endothelial barrier matrix where it may mediate stabilization of the pulmonary microvascular barrier remains to be determined. PMID- 4015233 TI - Total trapeziometacarpal arthroplasty. Report on seventeen cases of de generative arthritis of the trapeziometacarpal joint. AB - The authors have studied the results of 17 total trapeziometacarpal arthroplasties, performed in 15 patents between 1973 and 1983. The indications were essentially arthritis of the trapeziometacarpal joint either isolated or associated with peritrapezial lesions. The mean follow-up period was 3 years, the extremes ranged from 1 to 10 years. Results were judged as good in 13 cases, average in one case with 3 failures. Good results allow to recuperate complete mobility with adequate strength and stability.. The key point of this study was that first, cemented total arthroplasty does not represent a surgical escalade, a repeat operation is always possible in case of failure, and second, the concept of peritrapezial arthritis, and especially Crosby's stage 1 or stage 2 scaphotrapezial arthritis, is not a contraindication for total trapeziometacarpal arthroplasty. The best indications seems to be intense Dell's stage 3 or stage 4 trapeziometacarpal arthritis either isolated or associated with moderated peritrapezial arthritis. Two elements must be particularly studied before thinking about total trapeziometacarpal arthroplasty: the size, the consistancy and the configuration of trapezium; the degree of eventually associated scaphotrapezial arthritis. PMID- 4015231 TI - Septic complications of corticosteroid administration after central nervous system trauma. AB - The records of 197 consecutive multiple trauma patients were reviewed to define the infectious complications of corticosteroids used to treat brain and spinal cord injury. An injury severity score (ISS) and a central nervous system (CNS) injury score were determined for each patient. Patients with an ISS less than 20 did well with or without steroids and were excluded from further study. All deaths that occurred 5 or more days after injury were caused by sepsis, and all occurred in steroid recipients. Twenty-nine of 61 steroid-treated early survivors developed infectious complications, compared to eight of 55 patients who did not receive steroids (47.5% vs. 14.5%, p less than 0.001). There was no correlation between severity of CNS trauma and infectious complication rate. Steroid-treated patients frequently developed multiple pathogen primary infections and multiple, simultaneous septic foci. Patients treated with steroids more often developed infections caused by Staphylococcus aureus, assorted gram negative rods, anerobic bacteria, or fungi. The study strongly suggests a significant increase in both the incidence and severity of infectious complications occurring in patients treated with corticosteroids for CNS trauma. PMID- 4015232 TI - Neurogenic hypertension: etiology and surgical treatment. II. Observations in an experimental nonhuman primate model. AB - In a companion paper (Ann Surg 1985; 201(3):391-398), clinical data which suggest that neurogenic hypertension may be caused by arterial compression of the left medulla oblongata was presented. A chronic pathophysiologic animal model of neurogenic hypertension using a substitute for arterial pulsation, the neurovascular compression simulator (NCS), was developed. This paper presents data that demonstrate how development of hypertension in a nonhuman primate baboon (5 subject animals, 5 control animals) can be caused by the NCS, and the blood pressure can subsequently return to normal following cessation of NCS activity. These experiments show that pulsatile compression of the left ventrolateral medulla oblongata results in cardiovascular changes consistent with the sequence found in human neurogenic hypertension. Arteriosclerosis and arterial ectasia in the human contribute to arterial elongation and looping at the base of the brain. An arterial loop, by causing pulsatile compression of neural structures, elicits an increase in blood pressure initiated by an increase in cardiac output. This may be due to interference with the autonomic control of the heart and/or by alteration of the relative capacitance of the vascular system. PMID- 4015234 TI - The metacarpophalangeal stabilization test beevor or bouvier? AB - In a claw hand by ulnar and median nerve palsy if the digits are stabilized in order to prevent overextension of the metacarpophalangeal joints, the long extensor alone can fully extend all phalanges. Based on the proximal interphalangeal stiffness evaluated by this test (in more than 200 claw hands I have had the opportunity to operate in over 20 years), I would like to propose a simple therapeutic plan for palliative surgery. Some have recognized Beevor as the author of this test in 1903, but, it seems as though it was Bouvier who first described it in 1851. In any case, rather than using a name, why not just call it "the metacarpophalangeal stabilization test"? PMID- 4015235 TI - Hand injuries caused by high pressure injection. Contribution of loco-regional anaesthesia. AB - In a reported case of accidental high pressure injection of white spirit into a finger, the authors emphasise the great contribution of regional anaesthesia maintained from the initial trauma until the lesions are stable. Trauma to the hand caused by injection of paint or grease solvents results in tissue destruction and later necrosis and fibrosis. Secondary amputations are required in many cases. Regional anaesthesia of the stellate ganglion and brachial plexus produces analgesia and vasodilatation of peripheral arteries by inhibition of the sympathetic tone. This vasodilatation limits the necrotic process and promotes the supply of drugs to the injured tissues. Regional anaesthesia is of great benefit for surgical excision and avoids extended amputation. PMID- 4015236 TI - New facts about hand control-kinaesthesia. AB - In the cases of major losses, kinaesthesia has to be evaluated in reconstructive arm and hand surgery if adequate functional results are to be obtained. Differing from earlier teaching, experimental work has shown that the dominating afferent receptor system for proprioception is located in the skin, not in joints or in the musculotendineous system. This fact must be taken in account in planning surgery as well as in the following (re-)education and training. PMID- 4015237 TI - [Sarcoidosis of the hand]. AB - A case of a tumor-like lesion (pseudotumor) of sarcoidosis is reported. It was a recurrence of a soft tissue tumor in the hand. Diagnosis was made by pathological examination and led to the detection of the general disease. PMID- 4015238 TI - The extensor apparatus in Dupuytren's disease. AB - If we study the secondary changes in the extensor mechanism we can see changes at each of the three joint levels which are responsible for incomplete correction of the deformity after apparently adequate surgery on the palmar aspect. At the DIP level the flexion may not be restored until tenotomy of this secondarily contracted extensor tendon is performed. At the PIP level the middle slip may be used as a "lively splint" capable of progressive post-operative straightening of this joint if tenotomy over the middle phalanx is used. At the MP joint of the little finger ulnar subluxation of the extensor tendons may produce persistent MP flexion although passively correctable, and relocation of the extensors at this level may occasionally be indicated to correct this persisting disability. PMID- 4015240 TI - Comparison of the effectiveness of myocardial preservation in right atrium and left ventricle. AB - Ten patients underwent cardiac operations during which myocardial preservation was provided by systemic hypothermia, topical cardiac cooling, and cold blood cardioplegia. The duration of ischemia ranged from 45 to 142 minutes (mean, 84.2 +/- 36.2 minutes). Two serial specimens (preischemic and ischemic) were obtained from the right atrium and the left ventricle, respectively; thus, a total of 40 biopsy specimens was obtained from these 10 patients. A combination of grading of ischemic injury and stereological morphometric measurement of mitochondria was performed to assess the effectiveness of myocardial preservation. Our findings from the mitochondrial score studies (grading of ischemic injury) were as follows. In the right atrium, the average mitochondrial score rose from 0.337 +/- 0.235 in the preischemic stage to 1.969 +/- 0.492 in the ischemic stage. In contrast, the average mitochondrial score for the left ventricle was only elevated from 0.380 +/- 0.161 to 1.353 +/- 0.396. The difference between preischemia of the right atrium and left ventricle is not statistically significant, but the difference between ischemia of these chambers is significant (p less than 0.01). Our stereological morphometric studies revealed that in the left ventricle, the average mitochondrial surface area was 0.316 +/- 0.046 micron 2 in the preischemic stage and 0.347 +/- 0.073 micron 2 in the ischemic stage, a 9.8% increase in mitochondrial size (not significant). In contrast, the mitochondrial surface area of the right atrium showed a mean increase of 65.8%, from 0.231 +/- 0.038 micron 2 in the preischemic stage to 0.383 +/- 0.057 micron 2 in the ischemic stage (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4015239 TI - Effect of carnitine on myocardial function and metabolism following global ischemia. AB - Carnitine has therapeutic potential for the postischemic heart by facilitating the oxidation of acylated fatty acid metabolites, the intracellular accumulation of which has a deleterious effect on myocardial function and metabolism. To test this hypothesis, two groups of dogs were given preischemic treatment with carnitine, 50 mg per kilogram of body weight (Group 1) or 100 mg/kg (Group 2), and were compared with untreated controls (N = 12 for all groups). The canine hearts underwent 30 minutes of global 37 degrees C ischemic arrest with reperfusion. Left ventricular systolic and diastolic function was assessed by an intracavitary balloon while metabolic derangements were quantitated by serial myocardial biopsies assayed for adenosine triphosphate (ATP). Comparable 49 to 53% (p less than 0.01) declines in preischemic ATP levels occurred during the study period in the controls and both experimental groups. However, postischemic systolic left ventricular function was better preserved in Group 2: these hearts generated 61 +/- 3% of preischemic peak developed pressure compared with 37 +/- 4% in the controls and 42 +/- 3% in Group 1 (p less than 0.01 for each), and 60 +/- 2% of preischemic maximum rate of rise of left ventricular pressure as opposed to 45 +/- 4% in the controls and 49 +/- 6% in Group 1 (p less than 0.02 for each).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4015241 TI - The results of valve replacement for mitral valve prolapse. AB - Between January, 1975, and December, 1982, 33 patients underwent mitral valve replacement for mitral valve prolapse secondary to myxomatous degeneration. The majority were in the seventh decade of life (median age, 62 years), and all were seen with symptoms of mitral regurgitation. Echocardiography was more accurate in making the diagnosis of mitral valve prolapse more often (75%) than angiography (66%). Thirty-eight percent of the patients who underwent cineangiography had concomitant coronary artery disease and had coronary artery bypass grafting as well as mitral valve replacement. There was 1 operative death, an operative mortality of 3%. There were 6 late deaths, a late mortality of 18%. Of the 26 long-term survivors, 23 (88%) were in New York Heart Association Functional Class I and 3 (12%) were in Class II. The average length of follow-up was 33.25 months, and the 5-year actuarial survival was 76%. There was only one incident of thromboembolism (3%). Short-term and long-term survival were not related to the severity of mitral regurgitation but to the status of the left ventricle and the overall condition of the patient. These data suggest that older patients with severe mitral regurgitation secondary to mitral valve prolapse can undergo valve replacement with low operative mortality and gratifying long-term results. PMID- 4015242 TI - Changing trends in the surgical treatment of coarctation of the aorta. AB - From 1974 through 1983, 107 patients 4 days to 27 years old underwent 115 operations for treatment of coarctation of the aorta. Thirty-two patients were infants (1 year old or younger), and 28 of them were newborns. All newborns were seen with congestive heart failure. Seventy-one patients were seen with hypertension. Associated anomalies were present in 72 patients (67%). Resection was performed in 48 patients, patch aortoplasty in 16, bypass of the coarcted segment in 15, and left subclavian artery flap angioplasty (LSAFA) in 36. Ligation of a patent ductus arteriosus was simultaneously performed in 28 patients and pulmonary artery banding, in 4. Follow-up was 6 months to 9.2 years. There was a significant difference in aortic cross-clamp time between 26 patients who had resection (37.9 +/- 12.9 minutes) (mean +/- standard deviation) and 32 patients who had LSAFA (22.9 +/- 7.7 minutes) (p less than 0.05). Six patients died within thirty days after operation; 5 of them had resection, and 1 had bypass. Major postoperative complications included bleeding requiring exploration in 3 patients (2 after resection and 1 after LSAFA) and paraplegia in 1 patient after reoperation (resection) for recurrent coarctation 3 years after patch aortoplasty. Paradoxical hypertension was observed in 13 patients, and sustained systemic postoperative hypertension developed in 11 after effective repair of coarctation. There was no significant difference in early postoperative arm-leg pressure gradients between the types of operation or the various age groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4015243 TI - Reoperation for aortic coarctation: techniques, results, and indications for various approaches. AB - To define the safety and efficacy of operation for recurrent thoracic aortic coarctation, we reviewed the hospital records and subsequent courses of 53 patients who underwent such procedures over a 23-year period. Previous operations included end-to-end anastomosis, prosthetic patch or subclavian flap aortoplasty, and prosthetic interposition or bypass grafts, performed in patients ranging from 1 day to 44 years old. Several different reoperative procedures were used, including an ascending-descending aortic bypass graft in 4 patients who had had two previous repairs. There were no hospital or late deaths and only 3 relatively minor complications. Only 2 patients have hypertension requiring drug therapy at follow-up, which now averages 7 years. We conclude that operative management of severe, recurrent coarctation is both safe and effective, and that several techniques of reconstruction may have a place in such therapy. PMID- 4015244 TI - The value of computed tomography in staging bronchogenic carcinoma: a changing role for mediastinoscopy. AB - Forty-one patients underwent operative staging for bronchogenic carcinoma following computed tomography of the mediastinum between August, 1982, and March, 1984. Twenty-seven patients were classified as Stage I preoperatively; in 2 of them, positive mediastinal nodes were found at thoracotomy. For the 14 patients in whom positive nodes had been identified by computed tomographic (CT) scanning, staging was unchanged as a result of the findings at mediastinoscopy or thoracotomy or both. In this series, computed tomography had a sensitivity of 89%, a specificity of 100%, and an overall accuracy rate of 95%. We conclude that mediastinoscopy is not needed in patients without evidence of mediastinal nodal enlargement by CT scan; when performed, it should be guided toward those nodes identified as positive. PMID- 4015245 TI - The biological operability of stage III non-small cell lung cancer. AB - Stage III non-small cell lung cancer represents a broad spectrum of anatomical and histological subsets of patients with differing biological characteristics and prognostic expectations. Our experience with 161 consecutive patients undergoing complete resection for Stage III non-small cell lung cancer at the M. D. Anderson Hospital and Tumor Institute from 1965 through 1980 includes 69 patients with T3 N0 or N1 disease and 92 patients with an N2 classification. The cumulative 5-year survival overall was 30%: 35.6% for the T3 N0 or N1 group and 26% for the N2 patients. Seventy-three patients had squamous cell carcinoma and 76, adenocarcinoma. Small numbers of patients had other miscellaneous classifications (N = 12). In the T3 N0 or N1 subset, 43% of the patients with squamous cell carcinoma (N = 37) and 23% of those with adenocarcinoma (N = 25) survived 5 years. In the N2 subset, 39% of the patients with squamous cell carcinoma (N = 36) and 14% of the group with adenocarcinoma (N = 52) achieved long-term survival. Failure of treatment was clinically documented in 61 patients. The first observed recurrence or metastasis was at a distant site in the majority of these patients. Operative intervention for patients with Stage III M0 non-small cell lung cancer is effective and reflects the impact and limitations of resection on disease progression. Adjuvant irradiation was not shown to improve the outcome over the results of operation alone. Effective systemic therapy will be required to produce substantial changes in end results. PMID- 4015246 TI - Strut fracture and disc embolization in Bjork-Shiley mitral valve prostheses: diagnosis and management. AB - Mechanical failure of the Bjork-Shiley tilting disc prosthesis is a rare but catastrophic complication of the valve. Several previously reported cases of major strut fracture with disc embolization led to improvements in the structure of the prosthesis. A case of minor strut fracture in the improved convexoconcave model of the Bjork-Shiley mitral valve prosthesis is described. The literature on mechanical failures in the Bjork-Shiley mitral valve prosthesis is reviewed, and recommendations for recognition and management of this problem are made. PMID- 4015247 TI - Management of an infected mucocele occurring in a bypassed excluded esophageal segment. AB - An infected mucocele of an excluded retained esophageal segment is an infrequently reported complication of esophageal bypass surgery. The subtle symptoms of this entity and its management are discussed. PMID- 4015248 TI - Delayed closure of the median sternotomy incision. AB - Attempts to close a median sternotomy incision in the patient with profound cardiac or pulmonary dysfunction following a cardiac surgical procedure can result in severe hemodynamic deterioration. Delayed sternal closure in this setting may be a lifesaving technique. A method is described for delayed sternal closure that employs a temporary impermeable rubber patch sutured to the presternal fascia. PMID- 4015249 TI - Techniques to maximize mammary artery length. AB - The available length of the internal mammary artery has limited its versatility as a bypass conduit. Several techniques for increasing usable internal mammary artery length are described. PMID- 4015251 TI - Diathermy-induced loss of DDD pacemaker identity. PMID- 4015250 TI - Thoracic surgical problems in asbestos-related disorders. AB - Among 1,577 persons with asbestos exposure followed up from 3 to 30 years, 113 had thoracic surgical procedures for asbestos-related disorders. Twenty-six individuals suspected of having asbestosis with atypical features underwent open lung biopsy; a different disease was revealed in 14. Most of the 29 patients with mesothelioma had a small thoracotomy for diagnosis only; chemotherapy in half of them proved entirely ineffective. Experience with 23 patients with bronchogenic carcinoma did not differ from that in persons not exposed to asbestos. Problems of causal relationship are discussed. Most of the 68 individuals with benign asbestos pleural effusion had no symptoms, but because of recurrence, 15 were operated on for decortication or for possible mesothelioma. Hyaline plaques often were mistaken for lung, rib, or diaphragmatic tumors, and sometimes mesothelioma was suspected. Operative intervention in the 24 patients with plaques could have been avoided by obtaining a more detailed occupational history and reviewing previous chest roentgenograms, which invariably showed identical or smaller plaques from 2 to 17 years earlier. PMID- 4015252 TI - Identification of right coronary ostium. PMID- 4015253 TI - Closure of postpneumonectomy empyema space. PMID- 4015254 TI - Manual external aortic counterpulsation. PMID- 4015255 TI - Noncoronary collateral blood flow. PMID- 4015256 TI - Intracavitary coronary arteries. PMID- 4015257 TI - Selective decrease of hypothalamic noradrenaline by cysteamine. AB - In dose studies, cysteamine pretreatment in a dose of 200 mg/kg or 300 mg/kg (subcutaneously, s.c.) markedly decreased the hypothalamic noradenaline content, but did not influence the dopamine and serotonin contents. In time studies, pretreatment with cysteamine in a dose of 300 mg/kg (s.c.) led to markedly decreased hypothalamic noradrenaline contents 4 hr, 8 hr and 12 hr after treatment. These results suggest that cysteamine treatment selectively decreases the hypothalamic noradrenaline content in dose- and time-related manners. PMID- 4015258 TI - Effects of adenosine triphosphate on neuron activities in the lateral and medial vestibular nuclei. AB - Electrophysiological studies were carried out to elucidate the effects of adenosine triphosphate (ATP) on the vestibular nuclei of cats anesthetized with alpha-chloralose. Intravenous (i.v.) administration of ATP in doses of 0.5-2.0 mg/kg produced an enhancement of spike generation with vestibular nerve stimulation and spontaneous firing in both monosynaptic and polysynaptic neurons in the lateral vestibular nucleus (LVN) as well as in the medial vestibular nucleus (MVN). These effects of ATP, however, were not dose-dependent. In contrast, iontophoretic application of ATP up to 200 nA had only negligible effect on spike generation of mono- and polysynaptic neurons in the LVN and those in the MVN upon vestibular nerve stimulation. The results suggest that the enhancement of neuron activities in the vestibular nuclei following i.v. injection of ATP is due to the indirect effect probably resulting from an increase in blood flow in the brain, but not to a direct, excitatory effect of the drug on the neurons themselves. PMID- 4015259 TI - Adaptation of skeletal muscle energy metabolism to repeated hypoxic-normoxic exposures and drug treatment. AB - Muscular glycolytic fuels, intermediates and end-products (glycogen, glucose, glucose-6-phosphate, pyruvate, lactate), Krebs cycle intermediates (citrate, alpha-ketoglutarate, succinate, malate), related free amino acids (glutamate, alanine), ammonia, energy store (creatine phosphate), energy mediators (ATP, ADP, AMP) and energy charge potential were evaluated. Furthermore the maximum rate (Vmax) of the following muscular enzyme activities was evaluated in the crude extract and/or mitochondrial fraction: for the anaerobic glycolytic pathway: hexokinase, phosphofructokinase, pyruvate kinase, lactate dehydrogenase; for the tricarboxylic acid cycle: citrate synthase, malate dehydrogenase; for the electron transfer chain: total NADH cytochrome c reductase, cytochrome oxidase. The rat gastrocnemius muscles were analyzed in normoxia and after repeated, alternate hypoxic and normoxic exposures (12 hours of hypoxia daily; for 5 days). Naftidrofuryl was administered daily at three different doses: 10, 15 and 22.5 mg/kg i.m., 30 min before the beginning of the experimental hypoxia. The biochemical adaptation to intermittent normobaric hypoxic-normoxic exposures was characterized by the decrease of the muscular contents of creatine phosphate, citrate, alpha-ketoglutarate and glutamate. This adaptation occurred in absence of significant changes in the Vmax of the muscle enzymes tested. By naftidrofuryl treatment, in gastrocnemius muscle from hypoxic rats both alpha-ketoglutarate and creatine phosphate contents maintained normal values, while glutamate concentration remained reduced to subnormal values. With the exception of hexokinase, naftidrofuryl treatment did not modify the Vmax of marker enzymes related to energy transduction. PMID- 4015260 TI - The effect of ranitidine on exocrine pancreatic secretion in the rat. AB - The effect of the H2-receptor antagonist ranitidine on pancreatic exocrine secretion was studied in the rat. In anaesthetized animals with acute fistulas pancreatic secretion was induced by central (2-deoxy-D-glucose, 2-DG) or peripheral (acetylcholine) cholinergic stimulants and by cholecystokinin and secretin. In some experiments cimetidine was used as a reference compound. Ranitidine (20 mg X kg-1 intraperitoneally) did not change neither basal secretion nor the response to the combined hormonal stimulation. On the contrary, it significantly increased 2-DG and acetylcholine-stimulated secretion, whereas cimetidine (100 mg X kg-1 intraperitoneally) inhibited the pancreatic response to 2-DG. The different behaviour of the two H2-antagonists suggests that the effect of ranitidine is independent of the H2-receptor blockade and most probably connected with the cholinergic-like action of the drug. PMID- 4015261 TI - Cardiovascular effects of drugs acting on the autonomous nervous system, in awake, normotensive and hypertensive rats. AB - A study has been carried out in awake normotensive (WKY), spontaneously hypertensive (SHR) and renal hypertensive (RHR) rats in order to compare the reactivity of the autonomous nervous system using different indwelling catheterizations. In all cases, a jugular catheter was implanted for i.v. injections. The arterial cannula was implanted in the femoral artery (group 1) or in the right carotid artery (group 2), where the catheter was routed over 20 mm towards the heart, reaching the aortic arch. The plasma catecholamines levels were lower in the RHR than in the WKY or SHR, and whatever the strain, lower in group 2 than in group 1. In the WKY and the RHR, the mean blood pressure was higher in group 2 than in group 1. The tachycardia induced by isoprenaline and the pressor response to noradrenaline were higher in the SHR than in the WKY and in the RHR. By contrast, the reflex bradycardia was lower. Furthermore, the procedure of catheterization could modify the cardiovascular responses induced by adrenergic and cholinergic agents. These results demonstrate that indwelling catheterizations cannot be performed safely in the rat when studying effects on cardiac performance or vascular reactivity. PMID- 4015262 TI - Influence of verapamil on the digoxin-induced inotropic effect in guinea-pig isolated atria. AB - The nature of the digoxin-verapamil interaction was explored "in vitro" by determining the effect of verapamil on digoxin-induced inotropism in isolated guinea-pig atria. Verapamil, at concentrations (2.10(-8)-3.10(-8)M) too low to have any significant effect on the amplitude or frequency of the basal contractile activity, reduced the inotropic action of digoxin in all experimental circumstances, i.e. in spontaneously beating atria from reserpine-treated or untreated animals, in electrically driven (at 1 Hz frequency stimulation) left atria. The results obtained suggest that a competitive antagonism exists between verapamil and digoxin. In spontaneously beating atria an apparently competitive antagonism was also observed between verapamil and ouabain. The interaction observed between cardiac glycosides and the Ca++ channel blocker suggests that Ca++ movements across the sarcolemma may influence the inotropic effect of digitalis or its toxicity. PMID- 4015263 TI - Effect of aprindine, verapamil and nifedipine on ventricular fibrillation threshold in isolated rabbit hearts. AB - The effect of aprindine, verapamil and nifedipine on electrical stimulation threshold (EST) and ventricular fibrillation threshold (VFT) was studied in isolated rabbit hearts. Aprindine steeply raised EST and VFT in a dose-dependent manner. With the highest concentration of aprindine tested (0.56 mumol/l), protection against electrically-induced ventricular fibrillation was achieved in 4 out of 6 hearts after 60 min exposure to the drug. Perfusion with verapamil (0.1 and 0.2 mumol/l) and nifedipine (0.14 and 0.21 mumol/l) produced significant rise in both thresholds. When the hearts were perfused with higher concentration (0.3 mumol/l verapamil, 0.28 mumol/l nifedipine), EST and VFT did not continue to be increased in a dose-dependent manner but actually dropped below the control value in most hearts. These results suggest that the effect of aprindine on EST and VFT is different from that of verapamil and nifedipine and further indicate a limited effectiveness of these two slow channel blockers against ventricular fibrillation. PMID- 4015264 TI - Efficacy of disopyramide in comparison with verapamil and propranolol in the prevention of acetylcholine-induced atrial fibrillation in the dog. AB - The efficacy of verapamil and propranolol was studied in comparison with disopyramide on the atrial fibrillation experimentally induced in the dog heart in situ by electrical stimulation combined with intra-aortic injection of acetylcholine (ACh). After reducing the amplitude and duration of the monophasic action potential (MAP) and the duration of the effective refractory period (ERP) of the atrial contractile fibres, ACh lowered the fibrillation threshold (FT), and, when fibrillation had been elicited, it accelerated the fibrillation rate (FR). Verapamil and propranolol failed to prevent atrial fibrillation: they did not counteract any of the alterations in the electrophysiological properties of the atrial contractile fibres due to ACh. In contrast, disopyramide, at doses within the therapeutic range, prevented fibrillation. The fibrillation threshold, which fell from 50 mA to 1 mA in the presence of ACh, was restored to control values by disopyramide. Disopyramide also antagonized the reduction in amplitude of MAP caused by ACh before the triggering of fibrillation and the reductions by ACh of the durations of MAP and ERP. Disopyramide first slowed FR, in association with an increase in amplitude of fibrillation waves and a tendency to synchronous activity, and ultimately terminated the fibrillation. PMID- 4015265 TI - Therapeutic range for the control of oral anticoagulant therapy. PMID- 4015266 TI - Hypouricemia due to renal tubular defect. A study with the probenecid pyrazinamide test. AB - Hypouricemia with hyperuricosuria due to isolated renal tubular defects are rare conditions. Two patients with hypouricemia and hyperuricosuria were studied for derangements in the renal urate transport with the combined probenecid pyrazinamide test. In the first patient a significant decrease (64.5%) in the urate clearance--creatinine clearance ratio was noted after pyrazinamide administration, suggesting a post-secretory urate reabsorption defect, whereas the significant rise (44.2%) in urate clearance after the administration of probenecid indicates that this defect may not be complete. In the second patient there was a rise of 96.9% in the urate clearance--creatinine clearance ratio after the administration of probenecid and a decline of 31.6% in that ratio after pyrazinamide. These results suggest a defect in the presecretory reabsorptive site, with a highly significant response most probably of the postsecretory reabsorptive site to probenecid. PMID- 4015267 TI - Acute interstitial nephritis associated with mezlocillin, nafcillin, and gentamicin treatment for Pseudomonas infection. AB - Two patients developed acute interstitial nephritis (AIN) following treatment with mezlocillin sodium. Diagnosis was made by renal biopsy. Gallium 67 citrate scanning was abnormal in both. All patients were receiving multiple-drug therapy, but AIN has either not been described with the other drugs, or the temporal relationship between the AIN and termination of other drug therapy makes a causative relationship unlikely. All were infected with Pseudomonas aeruginosa. A role for the infecting organism or drug synergism in contributing to the renal disease cannot be excluded. PMID- 4015268 TI - Evaluation of silicone elastomer catheters for long-term intravenous chemotherapy. AB - We evaluated the efficacy and the complications of 65 silicone elastomer catheters inserted percutaneously for long-term venous access for administration of chemotherapy, antibiotics, and blood products in patients with metastatic cancer. Treatments were administered either in the hospital or in the outpatient clinic, using a portable infusion pump. The median indwelling time of catheters was 238 days (range, two to 521). The projected duration of catheter function, when the electively removed catheters were censured, was 310 days. Twenty-three catheters were removed because of malfunction, while the remaining either were discontinued electively (20) or were functioning at the conclusion of the study (22). The problems necessitating removal of 23 catheters were inadvertent dislodgement from loose sutures (eight), mechanical damage to the catheters (four), sepsis (four), phlebitis (four), intraluminal blockage with a clot (two), and cellulitis (one). We conclude that silicone elastomer catheters are safe and reliable for extended venous access for cancer chemotherapy. They are easy to insert and remove and can be replaced with a guide wire without requiring surgical intervention. PMID- 4015269 TI - Improved mortality in gram-negative bacillary bacteremia. AB - From 1979 to 1982, the four years of this study, episodes of gram-negative bacillary bacteremia occurred in a 489-bed community teaching hospital--an increase of 15.9%. Mortality related to bacteremia was 19.4% overall and only 3.2% for the 158 episodes involving nonfatal underlying illnesses, lower figures than those reported in the past. The severity of underlying illnesses in bacteremic patients dominated all other clinical variables that were studied as prognostic factors for the outcome of the episode. The same bacteremia-related mortality was seen in patients who had empirically received (1) multiple antibiotic regimens in which one or more drugs were active against the pathogenic organism(s), (2) either an appropriate aminoglycoside or beta-lactam antibiotic alone, or (3) both an aminoglycoside antibiotic and a beta-lactam antibiotic active against the pathogenic organism(s). PMID- 4015270 TI - Decreased platelet aggregation but increased thromboxane A2 generation in polycythemia vera. AB - Patients with polycythemia vera have been described to have hemorrhagic as well as thrombotic tendencies. In a patient with polycythemia vera and angina pectoris, we observed markedly decreased platelet aggregation response to epinephrine but increased platelet and whole-blood thromboxane A2 generation compared with normal subjects. Electron microscopy mostly showed partially activated forms of platelets, which may account for decreased aggregation response in vitro and hemorrhagic tendencies. Young and large platelets found in this disease, however, can generate large amounts of vasoconstrictor and platelet proaggregatory prostanoid thromboxane A2 in response to endogenous thrombin, which may be a basis for thrombotic tendencies. PMID- 4015271 TI - Pancreatic pleuropericardial effusions. Fistulous tracts demonstrated by computed tomography. AB - Demonstration of the fistulous tract linking pancreatic pseudocysts to the mediastinum and pleural cavity has diagnostic and therapeutic implications. In four cases, pseudocyst drainage through the esophageal and aortic diaphragmatic crus into the mediastinum and pleural cavity was delineated by computed tomography. In two cases, significant pericardial effusions were demonstrated. Computed tomography offers an effective diagnostic method when treatment is dependent on anatomic localization of the disrupted pseudocyst and its intrathoracic drainage tract. PMID- 4015272 TI - Cerebrospinal fluid Histoplasma antibodies in central nervous system histoplasmosis. AB - We have evaluated the Histoplasma antibody response in the cerebrospinal fluid (CSF) in nine patients with central nervous system histoplasmosis and 98 controls. While the CSF Histoplasma antibody response identified eight of the nine patients, CSF cultures were positive in only two. Of controls with histoplasmosis but without meningitis (13 patients), or without histoplasmosis (85 patients), elevated CSF antibodies were detected by complement fixation in seven, by IgG radioimmunoassay in 17, and by IgM radioimmunoassay in five. Measurement of the CSF Histoplasma antibody response appears useful for identifying meningitis in patients with histoplasmosis, although cross-reactions occur in half of patients with other forms of chronic fungal meningitis. Patients with these other infections can usually be identified by tests for CSF Coccidioides antibodies, or cryptococcal antigens. PMID- 4015273 TI - The support of clinical research and training by the National Institutes of Health. Introduction to the symposium. PMID- 4015275 TI - Ambulatory care training. The myth and the reality. PMID- 4015274 TI - Early diagnosis and treatment of medullary thyroid carcinoma. PMID- 4015276 TI - The 'chagrin factor' and qualitative decision analysis. PMID- 4015277 TI - The automated complete blood cell count. Use of the red blood cell volume distribution width and mean platelet volume in evaluating anemia and thrombocytopenia. AB - The availability of automated blood cell analyzers that provide an index of red blood cell volume distribution width (RDW) and a mean platelet volume (MPV) has led to new approaches to patients with anemia and thrombocytopenia. The RDW, which measures heterogeneity of the red blood cell population, complements the mean corpuscular volume in the differential diagnosis of anemia based on peripheral blood analysis. The MPV varies inversely but nonlinearly with the platelet count in normal individuals and is of value in assessing platelet production in the thrombocytopenic patient. The clinical applications of the RDW and MPV, which are currently reported on most routine blood cell counts, are discussed. PMID- 4015278 TI - Polymyalgia rheumatica. PMID- 4015279 TI - Physiology of the splanchnic circulation. AB - The splanchnic circulation is composed of gastric, small intestinal, colonic, pancreatic, hepatic, and splenic circulations, arranged in parallel with one another. The three major arteries that supply the splanchnic organs, cellac and superior and inferior mesenteric, give rise to smaller arteries that anastomose extensively. The circulation of some splanchnic organs is complicated by the existence of an intramural circulation. Redistribution of total blood flow between intramural vascular circuits may be as important as total blood flow. Numerous extrinsic and intrinsic factors influence the splanchnic circulation. Extrinsic factors include general hemodynamic conditions of the cardiovascular system, autonomic nervous system, and circulating neurohumoral agents. Intrinsic mechanisms include special properties of the vasculature, local metabolites, intrinsic nerves, paracrine substances, and local hormones. The existence of a multiplicity of regulatory mechanisms provides overlapping controls and restricts radical changes in tissue perfusion. PMID- 4015280 TI - The arrhythmias of digitalis intoxication. PMID- 4015281 TI - Hypercalcemia in leprosy. AB - We report a case of hypercalcemia in a patient with leprosy. Aminoterminal parathyroid hormone and 25-hydroxy-cholecalciferol concentrations were suppressed. Urinary hydroxyproline concentrations were elevated. There was no evidence of malignancy. The hypercalcemia resolved with corticosteroid therapy. PMID- 4015282 TI - Hyperkalemic distal renal tubular acidosis and selective aldosterone deficiency. Combination in a patient with lead nephropathy. AB - A patient with chronic renal failure, a strong history of moonshine abuse, and excessive urinary lead excretion had clinical and laboratory measurements compatible with combined hyperkalemic distal renal tubular acidosis and the syndrome of selective aldosterone deficiency. Extended treatment with fludrocortisone acetate, 0.1 to 0.2 mg/day, did not ameliorate acidosis or restore potassium excretion. PMID- 4015283 TI - Extramedullary hematopoiesis. A cause of severe generalized lymphadenopathy in agnogenic myeloid metaplasia. AB - Although microscopic evidence of extramedullary hematopoiesis in lymph nodes is a frequent finding in autopsy studies of patients with agnogenic myeloid metaplasia, clinically significant lymphadenopathy is a rare occurrence. In this article we describe an unusual case of severe generalized lymphadenopathy and lymphedema secondary to extramedullary hematopoiesis in multiple lymph nodes. With the use of low-dose radiotherapy, both the lymphadenopathy and lymphedema resolved. PMID- 4015284 TI - Massive hepatic necrosis after chemotherapy withdrawal in a hepatitis B virus carrier. AB - A chronic hepatitis B virus (HBV) carrier with diffuse nodular transformation of the liver and malignant lymphoma in the lymph nodes and spleen developed massive hepatic necrosis and died three weeks after the third cycle of chemotherapy. Immunosuppressive drug treatment may favor replication of HBV, resulting in massive hepatocyte destruction when the immune response recovers following withdrawal of chemotherapy. This outcome must be considered in patients with chronic hepatitis B who are treated with a course of prednisone followed by antiviral therapy as well as in HBV carriers following chemotherapy for malignant disease. PMID- 4015285 TI - The relative antihypertensive potency of propranolol, oxprenolol, atenolol, and metoprolol given once daily. A double-blind, crossover, placebo-controlled study in ambulatory patients. AB - The antihypertensive effect of four beta-blocking agents given once daily was compared with that of placebo in a prospective, crossover, double-blind study of 150 patients. The preparations tested were slow-release propranolol hydrochloride, 160 mg, atenolol, 100 mg, slow-release oxprenolol hydrochloride, 160 mg, and metoprolol, 200 mg. Propranolol and atenolol produced a significant decline in lying, standing, and postexercise blood pressure and pulse rate values. The effects of oxprenolol and metoprolol were not significantly different from that of placebo. PMID- 4015286 TI - Behcet's disease preceded by fever of unknown origin. PMID- 4015287 TI - Cerebral emboli of cardiac origin. PMID- 4015288 TI - Physician practices when a patient dies. PMID- 4015289 TI - C5 deficiency in a white family. PMID- 4015290 TI - Psychiatric patient referral. PMID- 4015291 TI - Epidemic outbreak of acute lead poisoning. PMID- 4015292 TI - Hypercalcemia and abnormal bone scan patterns. PMID- 4015293 TI - Phenytoin effects on liver and kidney structure of the rat. PMID- 4015294 TI - Cushing's syndrome produced by bronchial carcinoid associated with hypophyseal adenoma. PMID- 4015295 TI - Production of toxins A and B by Clostridium difficile strains isolated from infants and adults. PMID- 4015296 TI - Problems in management of Cushing's disease. PMID- 4015297 TI - Quantitative variations of melanin during the moulting of atypical fur in the volcano rabbit (Romerolagus diazi). PMID- 4015298 TI - Colchicine effect on intraperitoneal postoperative adherences. Experimental study on rats. PMID- 4015299 TI - Coagulation factors V and VII combined congenital deficiency in a Mexican family: Toledo-Tehuantepec deficiency, a new pathological entity. PMID- 4015300 TI - Morphological evidence indicating that C. cellulosae and C. racemosus are larval stages of Taenia solium. PMID- 4015301 TI - Serum immunoglobulins in acute poststreptococcal glomerulonephritis. PMID- 4015302 TI - [Differential diagnosis of vital and postmortem processes in burn cadavers]. AB - After presenting the most important intravitam reactions in 114 burnt corpses of the Gottingen autopsy material covering the years 1969-83 two cases are described with a) a so called burn haemorrhage in the stomach b) an extremely wide spreading of the upper thighs. Differential diagnosis and forensic significance of these findings according to chemical, histopathological and experimental examinations are discussed. PMID- 4015303 TI - [Findings in intermediate ridges of strangulation marks and their value as signs of vitality]. AB - Ecchymotic skin ridges, which are frequently found between the ligature turns in cases of dual or multiple loop ligature indicate to many authors hanging in life. Our examinations on an unselected group of corpses have led to the result that extravasations on the ridges between the ligature turns can be produced many hours after death, even outside the hypostatic area. In the case of prolonged suspension, small sub- and intra-epidermal blisters filled with serous fluid and fat may form on wide ridged strips between the ligature turns; the cells of the raised epidermis show significant large fat vacuoles. The bullous changes of the skin as well as the ridge ecchymoses can easily be reproduced in post mortem experiments. Therefore, both results cannot prove ante-mortem hanging. The paper presents four cases of suicidal hanging with vesication on the ridge between the ligature turns. PMID- 4015304 TI - Neither an enhancement of autolytic wall degradation nor an inhibition of the incorporation of cell wall material are pre-requisites for penicillin-induced bacteriolysis in staphylococci. AB - In contrast to what has been postulated, penicillin G at its optimal lytic concentration of 0.1 microgram per ml did not lead to a detectable activation of autolytic wall processes in staphylococci in terms of the release of uniformly labelled wall fragments from cells pretreated with the drug for 1 h. Rather a considerable inhibition of this release was observed. A similarly profound inhibition of the release of peptidoglycan fragments occurred when staphylococci pretreated for 1 h with 0.1 microgram penicillin per ml acted as a source of crude autolysins on peptidoglycan isolated from labelled normal cells of the same strain. This clearly demonstrated that the overall inhibition of autolytic wall processes caused by penicillin was mainly due to a decreased total autolysin action rather than to an altered wall structure. Furthermore, no substantial penicillin-induced inhibition of the incorporation of 14C-N-acetylglucosamine into the staphylococcal wall could be observed before bacteriolysis started, i.e., approximately during the first 80 min of penicillin action. These results are not consistent with any of the models hitherto proposed for the action of penicillin. PMID- 4015305 TI - A special morphogenetic wall defect and the subsequent activity of "murosomes" as the very reason for penicillin-induced bacteriolysis in staphylococci. AB - The actual reason for the penicillin-induced bacteriolysis of staphylococci was shown to be the "punching" of one or a few minute holes into the peripheral cell wall at predictable sites. These perforations were the result of the lytic activity of novel, extraplasmatic vesicular structures, located exclusively within the bacterial wall material, which we have named "murosomes". In untreated staphylococci the punching of holes into the peripheral wall is a normal process which follows cross wall completion and represents the first visible step of cell separation. Under penicillin, however, analogous holes are punched by the murosomes at sites of presumptive cell separation even if no sufficient cross wall material had been assembled before at this site (but had rather been deposited at other sites). Consequently, because of the internal pressure of the protoplast, lytic death is the inevitable result of this perforation of the protective peripheral wall. Hence, the real mechanism of penicillin-induced bacteriolysis in staphylococci is considered to be mainly the result of a special morphogenetic wall defect: bacteriolysis is taking place regularly when a cell separation process is no longer preceeded by sufficient cross wall assembly at the correct place. However, hypotheses which are based purely on some variations of overall biochemical processes like total wall enzyme activities or total wall synthesis are not regarded to be sufficient to explain this type of lytic death. PMID- 4015306 TI - Psychiatric disorders. A rural/urban comparison. AB - We studied rural/urban differences in the prevalence of nine psychiatric disorders from a community survey (part of the Epidemiologic Catchment Area Program) of 3,921 adults living in the Piedmont of North Carolina. Crude comparisons disclosed that major depressive episodes and drug abuse and/or dependence were more common in the urban area, whereas alcohol abuse/dependence was more common in the rural area. When prevalence for these disorders was stratified for age, sex, race, and education (factors that may confound urban/rural comparisons), a number of significant differences were identified, such as higher prevalence of major depression in female and white subjects and higher prevalence of alcohol abuse/dependence in the less educated subjects. A logistic-regression analysis was used to determine if significant urban/rural differences persisted when these potential confounders were controlled. Major depressive disorders were found to be twice as frequent in the urban area in this controlled analysis. PMID- 4015307 TI - A comparison of clinical and diagnostic interview schedule diagnoses. Physician reexamination of lay-interviewed cases in the general population. AB - We examined the level of agreement between diagnoses derived from data gathered by lay interviewers using the Diagnostic Interview Schedule (DIS) in a general population survey (the Epidemiologic Catchment Area project) and both DIS and clinical diagnoses made by psychiatrists. Overall percent agreement between the lay DIS and the psychiatrists clinical impression ranged from 79% to 96%. The chance-corrected concordance was .60 or better for eight of the 11 diagnoses. Specificities were all 90% or better. Sensitivities were lower, but lay results showed a bias for only two diagnoses: major depression was significantly underdiagnosed and obsessive illness was overdiagnosed. We compared the present results with those of previous studies from clinical settings. We explored possible reasons for disagreement and discussed the implications of the findings for psychiatric epidemiologic research. PMID- 4015308 TI - Comparison of the lay Diagnostic Interview Schedule and a standardized psychiatric diagnosis. Experience in eastern Baltimore. AB - We studied DSM-III diagnoses made by the lay Diagnostic Interview Schedule (DIS) method in relation to a standardized DSM-III diagnosis by psychiatrists in the two-stage Baltimore Epidemiologic Catchment Area mental morbidity survey. Generally, prevalence estimates based on the DIS one-month diagnoses were significantly different from those based on the psychiatric diagnoses. Subjects identified as cases by each method were often different subjects. Measured in terms of kappa, the chance-corrected degree of agreement between the DIS and psychiatrists' one-month diagnoses was moderate for DSM-III alcohol-use disorder (abuse and dependence combined), and lower for other mental disorder categories. The unreliability of either the DIS or psychiatric diagnoses is one potential explanation for the observed disagreements. Others include the following: insufficient or inadequate information (on which to base a diagnosis); recency of disorder; incomplete criterion coverage; overinclusive DIS questions; and degree of reliance on subject symptom reports. Further study of the nature and sources of these discrepancies is underway. This work should produce a more complete understanding of obstacles to mental disorder case ascertainment by lay interview and clinical examination methods in the context of a field survey. PMID- 4015309 TI - A comparison of two diagnostic methods. Clinical ICD diagnoses vs DSM-III and Research Diagnostic Criteria using the Diagnostic Interview Schedule (version 2). AB - In the context of a seven-year follow-up study, 171 former psychiatric inpatients and 158 subjects from the general population were interviewed twice, first with the German version of the Diagnostic Interview Schedule (DIS) (version 2), and second with a clinical interview using the Arbeitsgemeinschaft fur Methodik und Dokumentation in der Psychiatrie (AMDP) checklist to assign a clinical International Classification of Diseases (eighth revision) (ICD-8) diagnosis, independent of the DIS. With the clinicians' ICD-8 diagnosis as a measure of the quality of the DIS, the results indicate a sufficiently high overall specificity and sensitivity of the DIS as a case-finding instrument in a general population survey, and a surprisingly high concordance of most DIS diagnostic classes with comparable ICD diagnoses. Only for panic disorders (possibly due to different symptom and time criteria) and schizophrenia (possibly due to the strict probe system, the dependence on self-reports, and time criteria) was low sensitivity found. Because there is no DIS diagnostic category comparable with ICD-8 unipolar affective psychosis, a meaningful comparison of this ICD category with Research Diagnostic Criteria and DSM-III was not possible. PMID- 4015311 TI - The assessment of affective disorders in children and adolescents by semistructured interview. Test-retest reliability of the schedule for affective disorders and schizophrenia for school-age children, present episode version. AB - The reliability of assessment of Research Diagnostic Criteria and DSM-III axis I affective disorders in children and adolescents was studied using a semistructured diagnostic interview. The Schedule for Affective Disorders and Schizophrenia (SADS) for School-Age Children (Kiddie SADS) Present Episode Version, an adaptation of the adult SADS for children was used. Fifty-two subjects, aged 6 through 17 years, were interviewed in a test-retest format by one of three pairs of interviewers. Assessment of symptoms and composite scales of the depressive syndrome were determined to have acceptable reliability, as were three depressive diagnoses. Conduct disorder was assessed with high reliability. Four anxiety disorders and their composite symptoms were assessed with unacceptable reliability; only separation anxiety was assessed with acceptable reliability. The results of this study showed generally lower reliability of symptoms, scales, and diagnoses than did two studies of adults using the SADS. PMID- 4015310 TI - Birth-cohort trends in rates of major depressive disorder among relatives of patients with affective disorder. AB - As part of the National Institute of Mental Health-Clinical Research Branch Collaborative Program on the Psychobiology of Depression Clinical Study, 2,289 relatives of 523 probands with affective disorder were interviewed with the Schedule for Affective Disorders and Schizophrenia and diagnosed for major depressive disorder by the Research Diagnostic Criteria. Data were analyzed using life-table and survival methods. The findings suggest a progressive increase in rates of depression in successive birth cohorts through the 20th century and an earlier age at onset of depression in each birth cohort. A predominance of female depressives was found in all birth cohorts but the magnitude of female-male differences fluctuated over the decades. The existence of these trends is reported to stimulate further research. These findings are discussed in terms of possible gene-environment interactions. However, no conclusive causal inferences can be drawn pending further investigation. PMID- 4015312 TI - A proposed method for measuring change beyond symptoms. AB - The initial report of the Patterns of Individual Change Scales battery presented the rationale, development, and conceptualization of this measurement package. Empirical data supported the reliability and validity of the scales as measures of patient characteristics that extended beyond the symptomatic domain. This article presents more extensive reliability and validity data. Ratings on two new samples were collected, and the interrater reliability coefficients for the scales were again of appreciable magnitude. Discriminant validity was examined, as was the factor structure of the battery. The results suggested that the scales tap three distinct sources of variance. Comparisons with symptom measures and case illustrations indicated that the measurement of changes in patients' functioning beyond symptoms is necessary and viable. PMID- 4015314 TI - Diagnosis of psychiatric disorders in epidemiologic field studies. PMID- 4015313 TI - Lactate provocation of panic attacks. II. Biochemical and physiological findings. AB - Thirty-one of 43 patients with panic disorder or agoraphobia with panic attacks and none of 20 normal controls panicked in response to infusions of sodium lactate. Before receiving lactate, patients showed higher heart rates than controls and also signs of hyperventilation. During lactate infusion, patients who did not panic, nevertheless, developed higher lactate and pyruvate levels and greater ionized calcium and pH changes than controls. Lactate-induced panic attacks were regularly accompanied by biological changes consistent with hyperventilation and central noradrenergic activation and irregularly by elevation of plasma norepinephrine and cortisol levels. Panic attacks were not associated with changes in epinephrine or calcium levels or pH. Baseline arousal increased the likelihood of panic during lactate infusion. It is hypothesized that lactate-induced panic primarily involves central noradrenergic discharge with inconsistent peripheral manifestations. PMID- 4015315 TI - A proposed solution to the base rate problem in the kappa statistic. AB - Because it corrects for chance agreement, kappa (kappa) is a useful statistic for calculating interrater concordance. However, kappa has been criticized because its computed value is a function not only of sensitivity and specificity, but also the prevalence, or base rate, of the illness of interest in the particular population under study. For example, it has been shown for a hypothetical case in which sensitivity and specificity remain constant at .95 each, that kappa falls from .81 to .14 when the prevalence drops from 50% to 1%. Thus, differing values of kappa may be entirely due to differences in prevalence. Calculation of agreement presents different problems depending on whether one is studying reliability or validity. We discuss quantification of agreement in the pure validity case, the pure reliability case, and those studies that fall somewhere between. As a way of minimizing the base rate problem, we propose a statistic for the quantification of agreement (the Y statistic), which can be related to kappa but which is completely independent of prevalence in the case of validity studies and relatively so in the case of reliability. PMID- 4015316 TI - Lack of pharmacokinetic interaction of carbamazepine with tranylcypromine. PMID- 4015318 TI - Supervision of the psychotherapeutic process. PMID- 4015317 TI - Postdexamethasone cortisol levels and subgroups of affective illness. PMID- 4015319 TI - Neurological dysfunctioning in offspring of schizophrenics in Israel and Denmark. A replication analysis. AB - Neurological functioning was compared in children at risk for schizophrenia from samples recruited in Israel and Denmark. In both samples neurological signs were assessed in school-age children with one schizophrenic parent and a matched group of children with no mentally ill parents. Multidimensional Scalogram Analysis of data identified, in both samples, a radex structure of neurological functioning, radiating from motor to sensory-perceptual signs. In both samples, the gradient of neurological functioning differed between the offspring of schizophrenics and controls. For both the offspring of schizophrenics and controls, the largest number of children showed no or few signs of neurological dysfunctioning. A subgroup of the offspring of schizophrenics, but not the controls, showed multiple signs of neurological dysfunctioning that varied in pattern among individuals. PMID- 4015320 TI - Institutional rearing and diagnostic outcome in children of schizophrenic mothers. A prospective high-risk study. AB - Within a prospective, longitudinal study of offspring of schizophrenic mothers (so-called high-risk children), diagnostic outcome (schizophrenia, "schizotypal" personality disorder, other diagnoses, and no mental illness) was predicted by the mother's age at first hospitalization and by institutionalization during the first five years of life. Institutionalization was unrelated to adult psychopathology in a low-risk control group. These results are interpreted as supporting a diathesis-stress model of schizophrenic origin. PMID- 4015321 TI - Psychiatric illness in first-degree relatives of schizophrenic and surgical control patients. A family study using DSM-III criteria. AB - This report examines the risk for psychiatric illness in 723 first-degree relatives of schizophrenics and 1,056 first-degree relatives of matched surgical control patients. Diagnoses in patients and relatives were made "blind" to one another, using DSM-III criteria. Information on relatives was obtained from personal interview and/or hospital records. Results were analyzed using two levels of diagnostic certainty and with or without relatives on whom only hospital records were obtained. In all analyses, the risk for schizophrenia was significantly greater (at least 18-fold) in the relatives of schizophrenics v controls. Evidence was also found for an increased risk in relatives of schizophrenics for schizoaffective disorder, paranoid disorder, and atypical psychosis but not for unipolar disorder, anxiety disorder, or alcoholism. As defined by DSM-III, schizophrenia is a familial disorder; however, the increased risk for psychotic illness in relatives of schizophrenics does not appear to be confined to schizophrenia alone. PMID- 4015322 TI - Endorphin activity in childhood psychosis. Spinal fluid levels in 24 cases. AB - Twenty 2- to 13-year-old infantile autistic children (16 boys and four girls) and four 4- to 13-year-old children (two boys and two girls) with other kinds of childhood psychoses were compared with eight 6-month-old to 6-year-old normal children with regard to cerebrospinal fluid contents of endorphin fractions I and II. The psychosis groups showed higher mean cerebrospinal fluid endorphin fraction II levels, and 11 (55%) of the 20 autistic patients showed values higher than the highest in the group of normal children. There was a trend toward a correlation between high fraction II levels and self-destructiveness and decreased pain sensibility in the psychotic children. The results are regarded as preliminary but as warranting further research in this potentially fruitful field. PMID- 4015323 TI - Basal ganglia and limbic system pathology in schizophrenia. A morphometric study of brain volume and shrinkage. AB - The volume of several parts of the basal ganglia and of the limbic system was measured by planimetry of myelin-stained serial sections in postmortem brains of 13 schizophrenic patients and nine control cases. The medial limbic structures of the temporal lobe (amygdala, hippocampal formation, and parahippocampal gyrus) and the pallidum internum were significantly smaller in the schizophrenic group, whereas the pallidum externum showed only a modest trend toward volume reduction. The volumes of the putamen, nucleus caudatus, nucleus accumbens, and the bed nucleus of the stria terminalis did not differ between patients and controls. The volume reductions of the limbic temporal structures and of the pallidum internum of schizophrenics are interpreted as degenerative shrinkages of unknown etiology. PMID- 4015324 TI - Further evidence of abnormal non-rapid-eye-movement sleep in schizophrenia. AB - Very low levels of visually scored stage 4 sleep are found in 40% to 50% of acute and chronic schizophrenics. Stage 4 is a visual estimate of high-amplitude delta (0.5 to 3 Hz) electroencephalographic waves; these waves can now be measured directly and reliably by computer. In this pilot study, we carried out such measurement in the successive non-rapid-eye-movement periods (NREMPs). We also sampled and measured visually sleep spindles by NREMP; spindles constitute a second distinctive feature of the NREM electroencephalogram. In five unmedicated, recently rehospitalized schizophrenic patients we found reduced delta amplitude and abundance (and increased spindle density) in NREMP1 (also called "REM latency") as compared with ambulatory normal controls. NREMP1 was also abnormally short with an average length similar to that reported for major depression. These striking abnormalities of NREM sleep may underlie the abnormal rapid eye movement distributions sometimes found in schizophrenic and depressed patients. Further studies are required to evaluate the relation of these NREM abnormalities to psychopathology (and hence their utility as biological "markers") and to rule out confounding effects of hospitalization or undetected napping. PMID- 4015325 TI - Electroencephalographic sleep of younger depressives. Comparison with normals. AB - The electroencephalographic sleep of younger depressives (aged 20 to 44 years) was compared with that of an age-matched group of normals. The patients demonstrated many of the typical sleep changes reported for older depressed populations: shortened rapid-eye-movement (REM) latency; REM sleep activity alterations, with a shift to the early portion of the night (first REM period); reduced delta sleep; and sleep efficiency reductions marked by sleep-onset difficulties. The traditional scoring procedures were supplemented by automated REM and delta-sleep analyses that provided more precise delineation of these differences between patients and normals, particularly the distributions of REM activity and delta-wave patterning. PMID- 4015326 TI - Activity measures in anorexia nervosa. AB - Twenty-four-hour measurements of wrist and ankle kinetic energy expenditures were obtained on 20 hospitalized female anorectics during the first two weeks of their hospitalization. Kinetic energy was examined against measures of weight, depression, and Minnesota Multiphasic Personality Inventory scores in a regression analysis. Effect of cyproheptadine hydrochloride, amitriptyline hydrochloride, and placebo on activity was assessed. The results supported previous studies showing a positive relationship between weight gain and motor activity and challenge the commonly held notion that activity decreases in anorectics as their clinical condition improves. Motor activity was initially significantly suppressed by cyproheptadine and subsequently increased. PMID- 4015327 TI - Similarity of non-REM abnormalities in schizophrenia and depression. PMID- 4015328 TI - Plasma haloperidol levels: clinical response and fancy mathematics. PMID- 4015329 TI - The interpretation of plasma haloperidol concentrations. PMID- 4015330 TI - Scanning electron microscope studies of the rat mesenteric lymph node with special reference to high-endothelial venules and hitherto unknown lymphatic labyrinth. AB - Mesenteric lymph nodes of the rat were studied by scanning electron microscopy after arterial perfusion fixation. Observation was made mainly of the high endothelial venules (HEVs), inner cortex and medulla. The HEVs were distributed not only in the inner cortex, but also in the interfollicular areas in the outer cortex, extending to closely beneath the marginal sinus. Various surface structures of the HEV endothelial cells were recorded, from quite smooth to densely granular. Special attention was paid to endothelial cells with cytoplasmic ridges concentrated at the center of the cell apex. Lymphocytes were numerously attached to the luminal surface of the HEV. Many lymphocytes presumably under and after emigration through the HEV wall could be recognized. Hitherto unknown labyrinths densely filled with lymphocytes were demonstrated in the inner cortex. These tubular and saccular spaces lined by attenuated cells originated from beneath the germinal centers and from around the HEVs to pour into the medullary sinuses. The lymphatic labyrinths were differentiated from the sinuses by their lack of reticular cell trabeculae and by their containing almost exclusively small lymphocytes. It was proposed that lymphocytes in the blood in HEVs massively emigrate to the labyrinth, and via the medullary sinuses, enter the efferent lymphatics of the lymph node. In the medullary sinuses, some lymphocytes in association with a macrophage were found to extend wing-like processes, probably reflecting their activation. Large free cells extending laminar projections, but smooth in surface otherwise, were occasionally found. Their possible identity with the veiled cells (KELLY et al., 1978) was considered. PMID- 4015331 TI - A new method for scanning and transmission electron microscopy of synaptic vesicles isolated from the cerebral cortex. AB - Spheroid and flattened synaptic vesicles were isolated from the brain homogenate of guinea pigs by a modified purification method. For scanning and transmission electron microscopy, a simple dipping method of preparation was developed and used. The purest and richest fraction of synaptic vesicles was obtained from a 0.1 M sucrose fraction of density gradients. The pellets of synaptic vesicles were easily resuspended without aggregate after ultracentrifugation at 40,000 rpm for 5 min. The isolated synaptic vesicles were dispersed as a monolayer on the surface of a copper grid covered with Formvar membrane. Adequate contrast was obtained by metal impregnation of specimens and gold coating at magnifications as high as 100,000 times using an acceleration voltage of 25 to 40 kV. The specimens were fixed in 0.75% glutaraldehyde (0.1 M phosphate buffer, pH 7.3) and then postfixed in 1% osmium tetroxide. After dipping for 1 to 2 min each in tannic acid, phosphotungstic acid, lead citrate and uranyl acetate, they were dehydrated with graded ethanol and coated with gold by ion sputtering at 400 to 560 volts for 4 min. The preparation method is reported on and technical problems are discussed. PMID- 4015332 TI - Stratified laminae fenestratae (alveolus fenestratus endothelialis) in the glomerular capillaries of the mouse kidney. AB - The fine structure of the stratified lamina fenestrata of the mouse glomerulus was described in detail in both transmission and scanning electron microscopy. We propose to name the extremely developed structure of the stratified lamina fenestrata as the alveolus endothelialis. It consists of numerous small irregular spaces partitioned by thin cytoplasmic processes. Individual spaces communicate with each other through the fenestra surrounded by the cytoplasmic partitions. This structure occurs not only on the basal lamina but also on the perikaryal portion of the endothelium. The constant appearance of the alveolus fenestratus without association of any pathological or degenerative changes suggests that this structure represents a certain general and fundamental feature of the fenestrated endothelial cell. Possible mechanisms for the genesis of this structure are briefly discussed. PMID- 4015333 TI - Transformation of amoeboid microglial cells into microglia in the corpus callosum of the postnatal rat brain. An electron microscopical study. AB - An electron microscope study of the corpus callosum in postnatal rats of various ages was carried out to elucidate the fate of the amoeboid microglial cells. The cells present in the corpus callosum of younger rats (3-5 days) were round and showed an eccentric nucleus with marginal chromatin. They displayed numerous lysosomal granules and vacuoles in the cytoplasm. In older animals, i.e., from 7 days onwards some of the cells became oval so that by 15-20 days of age most of the cells were elongated and branched. In the latter, the cells showed a flattened or angular nucleus with dense chromatin clumps. The cytoplasm showed fewer lysosomal granules and vacuoles which were absent in cells of 20 day old animals. Quantitative measurements showed that there was a gradual diminution in the amount of cytoplasm at the cell body of amoeboid microglial cells with age, so that by the age of 20 days the cells were reduced to less than one-third of their original size as seen in 3 day old rats. The reduction of cytoplasm at the cell body is probably because it is channelled to the cytoplasmic processes which are evident in older rats. Some cytoplasm may have been extruded and phagocytosed by companion cell types. PMID- 4015334 TI - Ultrastructure of the radial components of the mouse optic nerve and its changes during Wallerian degeneration. AB - Radial components of the optic nerve of the mouse were studied by using thin sections and freeze-fracture replicas. The investigations were performed on normal optic nerves, as well as on those undergoing Wallerian degeneration following eyeball enucleation. Normal radial components in thin sections were observed as a series of light lines composed of small electron-lucent dots situated in the interperiod lines across the myelin sheath. They are frequently found in those parts of the myelin sheath lying near the outer and inner processes of the oligodendroglia. Radial components in freeze-fracture replica were observed as a parallel array of many ridges composed of a row of particles. The particles of radial components located in the deeper part of the myelin sheath lose their linear arrangement and fall into disorder in a relatively early post-operative period. The parallel array of rows of particles located closely beneath the outer processes of the oligodendroglia remained intact for a long period, even in a markedly distorted myelin sheath. The present observations suggest that the radial components are resistant against the disintegration of the myelin lamellae during Wallerian degeneration. PMID- 4015335 TI - Intercellular spaces in the lymph nodule associated epithelium of the rabbit Peyer's patch and appendix. AB - Intercellular spaces in the epithelium of the rabbit Peyer's patch and appendix were examined by scanning and transmission electron microscopy to elucidate their three-dimensional structure and their relationship to the reticular spaces in the underlying lymph nodule. Two types of intercellular spaces were distinguished: regularly arranged tubular channels and irregularly winding tunnels. The tubular channels were observed around normal enterocytes on the villi or internodular folds and apical portions of nodule domes. The channel spaces were lined with a successive arrangement of belt-like intercrestal surfaces of prismatic enterocytes and variously sized processes on the crests. The processes adjoining opposed crests formed a ladder-like structure or pectinate septa between neighboring channels. The irregularly winding tunnels were formed among processes of irregularly shaped cells corresponding to FAE cells (Bockman and Cooper, 1973) or M cells (Owen and Jones, 1974) in the nodule associated epithelium. In the appendix, the tunnels were frequently organized into two-story spaces, the adlumenal and basal spaces, which were incompletely separated by cytoplasmic processes. These tunnels continued by pores in the basement membrane to the reticular spaces in the underlying lymph nodules. Furthermore, the tunnels and the basement membrane pores constantly contained single or grouped free cells or their processes. The findings in the present study suggest that the tubular channels are intraepithelial compartments for the absorption of nutrients and fluid, and the irregular tunnels are an intraepithelial network of spaces for the housing of lymphoid cells coming from the underlying lymph nodule. PMID- 4015336 TI - Blood vascular bed of the rat pituitary intermediate lobe, with special reference to its development and portal drainage into the anterior lobe. A scanning electron microscope study of vascular casts. AB - Blood vascular beds of the rat pituitary intermediate lobes were reproduced by injection of low viscosity methacrylate media, and then observed with a scanning electron microscope. Although the intermediate lobes of newborn and pubescent rat were poorly vascularized, the adult rat intermediate lobe contained numerous capillaries forming a fairly independent network whose density, however, was not so great as in the anterior and posterior lobes. The vascular network of the intermediate lobe could be divided into two parts: a superficial plexus close to the anterior lobe, and a deep one close to the posterior lobe, though the two plexuses were continuous with each other. The superficial plexus consisted of anastomosing capillaries, and the deep one of non-anastomosing capillaries with a palisade-fashioned arrangement. The superficial plexus seemed crucially important for the blood supply of the intermediate lobe since it developed or thickened as the animals aged. The superficial plexus received its proper afferent vessels from the middle and posterior hypophyseal arteries and emitted its proper efferent vessels continuous with the sinusoidal capillaries of the anterior lobe. The capillaries of the deep plexus usually communicated with the arterial capillaries of the posterior lobe and possibly represented another afferent route to the superficial plexus. This paper, thus, strongly suggests a portal circulation from the intermediate lobe to the anterior lobe though its functional significance is unknown. PMID- 4015337 TI - Electron microscope study of the Grandry and Herbst corpuscles in the palatine mucosa, gingival mucosa and beak skin of the duck. AB - Grandry and Herbst corpuscles of the palatine mucosa, gingival mucosa and beak skin were studied with the electron microscope. Typical Grandry corpuscles are surrounded by thick bundles of collagen fibers and composed of a terminal axon sandwiched between Grandry cells. Occasionally, two or three nerve endings are found within one corpuscle. The Grandry cell contains numerous electron-dense granules similar to those of a Merkel cell. The cell extends protrusions at the poles and the opposing faces. Desmosome-like attachments are noted between interdigitated protrusions, and between the axon and Grandry cell. Herbst corpuscles are composed of an outer capsule, inner core and central nerve ending. The outer capsule consists of 15 to 20 concentric lamellae, while the inner core possesses 60 to 70 sheets of cytoplasmic extensions. Under the scanning electron microscope, the corpuscles appeared as an elongated oval form surrounded by dense fibrous connective tissue, and each lamella of the outer capsule was composed of a dense network of thick and thin fibrils. These were seen under the transmission electron microscope as thick fibrils about 50 nm in diameter and peripheral thin fibrils about 10 nm in diameter. In some portions, a periodic increase of cytoplasmic density about 20 nm in width located in neighboring sheets was noted. The terminal axons of both corpuscles contain numerous neurofilaments, slender mitochondria, neurotubules, smooth endoplasmic reticulum and vesicles. Both corpuscles are limited by several flat cells which are arranged in parallel and probably correspond to the perineural cells of the peripheral nerve. Tight junctions were observed between these cells. PMID- 4015338 TI - [Thiophene as a structural element of physiologically active substances. 14. The synthesis of 5-[(5-methyl-3-thienyl)oxy]-2(1H)-pyrimidinone]. PMID- 4015339 TI - [Drug analysis by polarographic methods. 24. The polarographic behavior of tofisopam]. PMID- 4015340 TI - Simultaneous femoral and tibial lengthening for limb length discrepancies. AB - Simultaneous lengthening of the femur and tibia can be effectively and safely accomplished. However, the following issues must be kept in perspective: (1) patient selection is essential, and (2) meticulous attention to detail in all aspects of the operative procedure is vital. The advantages of performing such an ambitious operation include: (1) reduced morbidity, (2) reduced number of operations (not procedures), and (3) more rapid recovery when compared to performing the operations sequentially. This kind of program should be carried out only by those experienced in the limb lengthening procedure. PMID- 4015341 TI - Glass-ceramic metal composite bone fixation: effect of surface parameters. AB - The purpose of this study was to compare the rates of bone growth with four different surfaces of cobalt-chrome implants. Two of the implant surfaces were coated by a glass-ceramic of our own composition. One coating was porous. No enhancement of bone ingrowth was found in the glass-ceramic implants. The degree of metal ion contamination was also assessed, and significant, potentially harmful contamination by metal ions was found in the glass-ceramic. This study points out the need for better techniques of coating metal with glass-ceramic to avoid potential carcinogenic effects. PMID- 4015342 TI - Unicompartmental knee replacement in osteoarthritis: an 8-year follow-up. AB - Between 1972 and 1974, 34 patients with medial osteoarthritis in the knee were operated on with unicompartmental femorotibial replacement. Four patients were reoperated on, three of whom had had a McIntosh inlay prior to the operation. Seven patients had died and two were lost at the follow-up which took place on average 8 years (7-10 years) after the operation. Of 21 re-examined knees, 14 were rated as successful or acceptable. PMID- 4015343 TI - Dislocation following total hip arthroplasty. AB - The rate of postoperative dislocation after Stanmore total hip arthroplasty in 427 cases was 4.9%; 1.4% were classified as recurrent cases. Retroversion of the acetabular component and postoperative joint laxity were the only factors that were found to predispose to dislocation. The importance of preserving the effective femoral neck length during total hip arthroplasty is emphasized. PMID- 4015344 TI - Segmental spinal instrumentation without sublaminar wires. AB - We have developed a method of segmental spinal instrumentation that precludes the passage of sublaminar wires, thus reducing the likelihood of neurological complications. The technique utilizes the base of the spinous process as the purchase site for segmental fixation and a newly developed button-wire implant. The technique and early experience with this method are described. PMID- 4015345 TI - Stress in the human ankle joint: a brief review. AB - The articular bones of the ankle joint are subjected to stress along their vertical axis by the resultant force Rt [13]. On this compressive stress is superimposed bending resulting from tensile forces exerted by the collateral ligaments. The loading by tensile forces is greatest in the lateral areas of the joint, especially at the fibular malleolus. The bony elements of the ankle joint are adapted to this specific mode of stress by the distribution of osseous material in the subchondral bone and by cancellous architecture. Results from photoelastic model tests correspond to the morphological findings if models are subjected to stress by both compressive forces and tensile forces. Zones with high fringe orders of isochromatics in the model correspond to areas with high density of the osseous tissue in equidensity pictures, and the trajectorial pattern in Plexiglas models mirrors the alignment of compressive and tensile cancellous trabeculae. PMID- 4015346 TI - Anterior advancement of the tibial tuberosity in the treatment of the patellofemoral pain syndrome. AB - Seventy-two patients with disabling patellofemoral pain were treated with anterior advancement of the tibial tuberosity. In a follow-up examination 1-5 years (mean 2.5) postoperatively, 57% of the patients had improved, 19% were unchanged, and 24% were worse. The high failure rate is disturbing, and we warn against too frequent use of the anterior tuberosity advancement procedure. Patients with patellofemoral pain should be approached by establishing a specific diagnosis and applying a specific treatment. In this study we concluded that the only patients who might benefit from the operation were those with grade I-II changes of the patellar cartilage. PMID- 4015347 TI - Prediction of long-term outcome of tibial osteotomy in medial gonarthrosis. AB - To predict the long-term outcome after tibial osteotomy for medial gonarthrosis, multivariate statistical techniques were used and prognostic equations were defined. A comparison between different evaluation systems was also performed. Clinical and radiographic data from 81 patients followed up for more than 7 years were used. Twenty-eight preoperative variables were analysed in relation to the outcome at 7 years with the multivariate procedures discriminant analysis and cluster analysis. Among the variables, knee flexion and walking capacity were found to be the most dominant factors. Excluding the undercorrected osteotomies, preoperative walking capacity was now the dominating variable for prediction. Seven years postoperatively only small differences were found between the evaluation criteria of pain relief, London Hospital score, and HSS score. The discriminant functions for the highest ranked evaluation criteria are given in the text, as are dendrograms showing the patterns of interdependence between the evaluation criteria. Thus it was possible to transform clinical entities into factors suitable for determination and calculation of postoperative evaluation. The most commonly used evaluation systems had very similar discriminant functions showing good agreement. PMID- 4015348 TI - The comparative properties of plaster of Paris and plaster of Paris substitutes. AB - Modern casting materials are becoming available in an increasing and bewildering variety. A series of tests has been devised to investigate the properties of these materials. They have been tested for strength, flexibility, lamination, fatigue life and radiolucency. Their properties have been compared with those of plaster of Paris in order that the role of the newer materials can be defined. It is suggested that the tests described might form the basis of a standard from which user trials could be designed to appraise the value of these materials in clinical practice. PMID- 4015349 TI - High incidence of low serum vitamin D concentration in patients with hip fracture. AB - The study of 82 consecutive hip fracture patients (22 males and 60 females) and 185 various controls showed that low serum 25-OH-vitamin D3 (25-OD-D3) concentration was common in the hip fracture patients, who in addition were old, incapable of independent daily life, had poor dietary habits, reduced nutritional status, and spent insufficient time in sunlight. The most usual mechanisms of trauma were minor indoor falls. Osteoporosis was common and associated with low 25-OH-D3. Hypocalcemia was more common in hip fracture patients than in controls. Increased serum alkaline phosphatase was not a specific feature in hip fracture patients. The results suggest that vitamin D supplementation is indicated in elderly disabled people. PMID- 4015350 TI - Septic arthritis of the acromioclavicular joint. AB - A patient with isolated pyogenous arthritis of the acromioclavicular joint (A-C joint) caused by Streptococcus viridans is described. The patient had no underlying disease. Minor trauma preceded shortly the development of the septic process. The patient was treated successfully with surgical drainage and antibiotics. To our knowledge this is the first case report of septic arthritis of the A-C joint caused by Streptococcus viridans. The A-C joint is rarely involved in septic processes. Even conditions such as intravenous drug abuse [3, 6] and renal dialysis [4, 7] which tend to infect unusual joints [5] have only rarely been described in association with A-C septic arthritis. PMID- 4015351 TI - Factors influencing referral decisions in physiatry. AB - As the population ages and more emphasis is placed on patient management than on curative exercise, physical medicine gains an important place in medical specialties. This study investigates the referral behavior in physiatry and compares it with referrals to other specialties. From a sample of 159 primary care physicians in the St. Louis metropolitan area who have a high probability of using physical medicine and rehabilitation, a referral model in physiatry was constructed. The results indicate that while the traditional determinants of referral decision play a significant role in influencing the referral behavior in physiatry, there also is a group of variables in physiatry that are significantly different from those of other subspecialties in determining referral process. PMID- 4015352 TI - Daily energy expenditure and basal metabolic rates of patients with spinal cord injury. AB - Basal metabolic rate (BMR) and daily energy expenditure were measured in 48 men with complete traumatic transections of the spinal cord. Subjects were classified according to their residual motor function as high or low quadriplegic (HQ, LQ) or as high or low paraplegic (HP, LP). Measured BMR was lower than predicted BMR in almost all of the subjects and was significantly lower in the HQ group than in the other groups. High quadriplegics also expended significantly less energy while awake and over a 24-hour period than did the other groups. Measurements of BMR and total energy expenditure were significantly correlated with the level of lesion. The data provide a basis for establishing guidelines on the average energy needs of patients with spinal cord injury. PMID- 4015354 TI - Assistive devices: utilization by children. AB - The use of assistive devices by children has become widespread and has been supported financially by insurance carriers and governments. However, there has been little evaluation of the utilization of these devices. To determine utilization of, satisfaction with, and perceived value of the aid, an independent evaluator contacted 502 families who had used a provincial government funding program to obtain an assistive device. High levels of use, satisfaction, and perceived value were reported, indicating that a decentralized funding program can provide aids effectively. PMID- 4015353 TI - Parent perceptions of problems experienced by their children in complying with treatments for juvenile rheumatoid arthritis. AB - Parents of children with chronic diseases, such as juvenile rheumatoid arthritis (JRA), are responsible for insuring that their children comply with medical regimens. Assessing the perceptions parents have of problems their children experience in complying with treatment would be useful in advising them of how to help their children. In this study, a questionnaire assessing the frequency and type of problems children experienced in complying with treatments of JRA was completed by 37 parents. The parents reported more problems with range of motion exercises and splint wearing than with medications. The most common negative reactions exhibited by the children included complaining, crying, forgetting to do what was prescribed, and noncompliance. Additionally, nearly 50% of the parents relied on their child's report or were vague about how they assessed compliance. Suggestions for advising parents about how they can assess and improve compliance are offered in this report. PMID- 4015355 TI - Wheelchair push-ups: measuring pressure relief frequency. AB - Ischial pressure sores (PS) are a long-recognized complication of wheelchair confinement, yet teaching spinal-cord patients to establish lift-off behavior habitually and permanently remains a challenge. A new device was developed to record automatically and continuously the wheelchair lift-off behavior of spinal cord injured patients. Data from seven patients who used the device for between 768 and 1800 hours each are reported. The device was used to monitor longitudinally the behavioral compliance of each individual with prescribed lift off intervals using standard teaching procedures. Wide variability between patients and within patients over time was found. Experimental interventions including the use of an electronic timer and written and oral feedback of the previous day's data also varied in their effectiveness. Data from one patient who developed a pressure sore while being monitored suggest that there is no simple relationship between lift-off intervals and PS formation. PMID- 4015356 TI - Exercise or overloading: effect on skeletal muscle grafts of rats. AB - The effects of increased usage on regenerated muscle grafts was studied in rats. Soleus muscles were grafted orthotopically, either without neuromuscular anastomoses (standard grafts), or with their original nerves undamaged (nerve intact grafts). The rats were either run on a treadmill or their soleus grafts were overloaded by extirpation of approximately 50% of the gastrocnemius muscles. Twitch and tetanic contractions, glycogen concentration, and histological features of the grafts were evaluated 60 days after grafting. The results showed that exercise enhanced glycogen levels in nerve-intact grafts as in normal muscle. Overloading had no effect on glycogen. The nonexercised standard grafts had the lowest values for the mechanical parameters studied. However, this was apparently due to the smaller degree of innervation rather than from the lack of exercise. Within the population of nerve-intact grafts, neither exercise nor overloading significantly improved the twitch and tetanic tensions. It is concluded that exercise, but not overloading, is likely to have positive effects on muscle graft metabolism. PMID- 4015357 TI - Grief in chronic illness: assessment and management. AB - Grief is a normal reaction to the loss of physical function. Its symptoms, however, are often mistaken for major depressive episode and treatment may be inappropriate. Symptoms of grief include a preoccupation with the lost object (a limb, a function, a loved one), somatic distress, inappropriate behavior, hostility, and denial. Depression may be a manifestation of illness or drug therapy. Grief should be treated like a major depressive episode but without antidepressive medications. The first step in management of grief is the development of a proper therapeutic milieu which will encourage the reappearance of self worth. Once the milieu is established, specific rehabilitation problems can be addressed. In formulating a prognosis, it is important to consider the severity of the patient's disability, the premorbid psychologic make-up, and the type of family and community support available to the patient. PMID- 4015358 TI - Self-directed learning and medical rehabilitation: a comparison. AB - A comparison is made between medical rehabilitation and continuing medical education (CME). It is hypothesized that such a comparison can help physicians who have little formal training in educational methodology to become more efficient and effective in carrying out their own self-directed learning. This hypothesis is based on the premise that the decision-making processes are similar for managing the medical rehabilitation of a patient and for carrying out self directed CME. PMID- 4015359 TI - Manual stimulation of reflex voiding after spinal cord injury. AB - Thirty-four urodynamic studies were performed in 20 patients with spinal cord injury (SCI) to determine the most effective triggering mechanism for reflex voiding. The studies were performed at a time when the patient was normally scheduled for catheterization, which avoided stimulation of the detrusor and sphincter by bladder filling via a catheter. The three methods chosen were used in a random sequence. Suprapubic tapping and jabbing were equally effective in producing a rise in detrusor pressure, and the sphincter responses were almost identical. Cutaneous stimulation of the thigh rarely produced any change in detrusor and sphincter activity. When detrusor contractions were produced, a dyssynergic sphincter response prevented voiding in 46% of the studies; however, voiding always occurred when the sphincters were either coordinated or showed no change. Both tapping and jabbing were more effective as the time from injury increased, which reflects the natural recovery from spinal shock. PMID- 4015360 TI - Diabetic Charcot spine as cauda equina syndrome: an unusual presentation. AB - Some 6% to 21% of Charcot joints occur in the spine. The underlying disease is usually tabes dorsalis, but diabetes mellitus is another etiology. Degeneration of spinal elements is accelerated and lumbar spinal stenosis with weakness may occur, as has been reported in tabetic arthropathy. The case presented is unusual in two respects: first, the Charcot spine was secondary to diabetic complications, which resulted in a compressive cauda equina syndrome; second, the patient presented with progressive paraparesis and bowel and bladder dysfunction but physical examination by several examiners revealed no clinically evident sensory abnormality. The patient had vague and inconsistent sensory complaints for several years preceding definitive workup, but the overall picture of his disease process only could be made following multiple laboratory, electrodiagnostic, microbiologic, and radiologic testing. The patient presented with subacute paraparesis, providing a wide differential diagnosis ranging from Guillain-Barre syndrome to spinal neoplasm. The physical, radiologic, laboratory, electrophysiologic, histologic/pathologic findings, treatment, and recovery status are included in this report. PMID- 4015361 TI - Posterior interosseous nerve syndrome caused by an intermuscular lipoma. AB - The posterior interosseous nerve is prone to entrapment at various anatomical sites along its course in the upper forearm. A variety of lesions may account for this resulting nerve palsy. Compression of the nerve by lipomata is uncommon; 16 such cases have been reported in the medical literature. We present a case of a lipoma causing pressure on the deep branch of the radial nerve. In this case, and in seven similar cases previously reported in detail, the mass became visible after the onset of finger and hand extensor muscle weakness. Hence, the possibility of nerve compression by a tumor must be suspected in the differential diagnosis. Paralysis that does not respond to four to six weeks of conservative treatment necessitates surgical intervention in order to assure maximum recovery of the affected nerve. PMID- 4015362 TI - Adaptive device for the quadriplegic golfer. AB - Participation in sports by the individual having quadriplegia is often limited because of the loss of use of intrinsic and extrinsic muscles of the hand. An adaptive device has been developed to enable quadriplegic patients to participate in a golf program. It consists of a molded forearm cuff of Kydex thermoplastic, to which a golf club is attached by several clamps and a golf glove altered by sewing velcro pile to the tips of all fingers and to the back of the glove. These have provided stability to the golfer's grip of the club, and have made it possible for quadriplegic patients to play successfully on the Par 3 golf course at the Medical Center. PMID- 4015363 TI - Is surgery worthwhile? PMID- 4015364 TI - Improved results with diabetic below-knee amputations. AB - This study of 100 consecutive below-knee amputations in 98 diabetic patients was undertaken to review our results and to compare them with a similar report of 20 years ago. Ninety-three limbs were ischemic, and 79% of the patients had significant infection. This finding was similar to that in our previous study group. Twenty-one percent of the patients had previous arterial reconstruction, 11% had had a toe or metatarsal amputation, and 17% required a guillotine (open) amputation to control sepsis. The below- to above-knee amputation ratio was 2.3/1. The selection of level was made on clinical grounds. None of the 100 amputations required revision to above-knee amputation. The mortality rate was 3% and the wound complication rate was 18%. Eighty-three percent of the patients were ambulatory at the time of discharge, which occurred at an average of 35 days. There has been a significant improvement in the number of successful below knee amputations performed since our previous study. We attribute these results to aggressive surgical control of infection and to close follow-up with early recognition and treatment of healing problems. PMID- 4015365 TI - Does the surgeon's annual case load make a difference in the quality of peripheral vascular surgery? A report of the mortality, morbidity, and long-term results of 101 procedures performed over 93 months. AB - The outcome of 101 peripheral vascular procedures performed during 93 months was reviewed to determine the quality of the results. Quality was defined as the following: series mortality rate, frequency and significance of complications, cumulative patency rate for bypass grafts, amputation rate, survival following abdominal aneurysm surgery, and neurologic events associated with carotid procedures. The series mortality rate was 4%; 44 procedures were free of complications; patency rates were not significantly different from published reports; the initial amputation rate was 7.4%; and only one out of ten patients was known to have died following aneurysm surgery. Neither of the two carotid procedures included neurologic complications. These data suggest that factors other than a surgeon's annual case load may influence the quality of the results and point out the need to further study this question in light of current admission criteria for the vascular surgery examination. PMID- 4015366 TI - Primary arteriovenous fistulas of the abdomen. Their occurrence secondary to aneurysmal disease of the aorta and iliac arteries. AB - We present three cases of arteriovenous fistula secondary to aneurysmal disease. The first patient, a 75-year-old man, presented with abdominal pain, a large pulsatile mass, and renal failure. He underwent repair of his aortocaval fistula; his renal failure resolved and the remainder of his course was uneventful. The second patient, a 77-year-old man, presented with a several-day history of nausea, lower abdominal pain, and a pulsatile mass. He underwent repair of his aortocaval fistula but died on the 21st postoperative day of progressive pulmonary failure. The third patient, a 76-year-old man, presented with an episode of syncope and subsequent rapid development of left lower extremity edema. He was subsequently found to have a right iliac artery to left iliac vein fistula, which was repaired. He did well postoperatively with gradual resolution of his lower extremity edema. PMID- 4015367 TI - Sutureless intraluminal graft for repair of abdominal aortic aneurysm. AB - A series of seven patients undergoing elective repair of abdominal aortic aneurysms using sutureless intraluminal aortic prostheses for infrarenal tube grafts was reviewed. Follow-up was five to seven months. There was no morbidity related to the graft and one late mortality. In the uncomplicated cases, the average total operative time was two hours 14 minutes with no bank blood transfusions. The overall average operative time was two hours 41 minutes with an average operative transfusion of 0.28 units and total transfusions of 1.70 units of bank blood per case. Based on this experience and the observation that operative time and blood loss are major determinants of mortality with emergency abdominal aortic aneurysm repairs, we believe that use of sutureless intraluminal prostheses in suitable cases of leaking or ruptured abdominal aortic aneurysms has the potential to markedly improve survival. PMID- 4015368 TI - Retroperitoneal inflow procedures for iliac occlusive vascular disease. AB - We reviewed our experience over the past six years with retroperitoneal inflow procedures (aortofemoral and iliofemoral bypass grafts) in high-risk patients with aortoiliac occlusive disease. There were 57 limbs in 40 patients. Twenty percent of the patients were diabetic, 80% were smokers, 40% had heart disease, 54% had hypertension, and 25% had symptomatic chronic obstructive pulmonary disease. The average patient age was 64 years. There was no operative mortality and cumulative patency rate by life-table analysis at four years was 84%. The site of the proximal anastomosis (aorta vs iliac) or the configuration of the graft (unifemoral vs bifemoral) did not influence the patency rate. Retroperitoneal inflow procedures are an excellent alternative in patients who present an unacceptably high risk for standard aortofemoral reconstruction. PMID- 4015369 TI - Venous stasis ulceration. Effectiveness of subfascial ligation. AB - Forty-seven extremities with recurrent venous ulceration were treated by subfascial ligation of incompetent perforating veins. The limbs were observed for an average of 8.5 years (range, 0.5 to 13 years). The risk for recurrence was 22%, 41%, and 51% at 1, 3, and 5 years, respectively. Patients with bilateral ulceration or prior venous ligation were at the highest risk for recurrence, while those with prior excision of prominent varicose veins had a reduced risk. There has been no loss of limbs or life secondary to this venous problem during the 398 cumulative years of observation. PMID- 4015370 TI - A comprehensive approach to extremity vascular trauma. AB - A review of our experience with 368 patients with 382 extremity injuries has resulted in a treatment plan resulting in improved patient care and limb survival. A thorough examination of the injured extremity will help diagnose a significant vascular injury in the presence of certain clinical findings, eg, bruit or thrill (100%), signs of acute ischemia (100%), absent pulse (91%), shock (89%), neurologic deficit (78%), and hematoma (55%). Arteriography in proximity injuries has resulted in an abnormal finding in 16% of cases. A total of 165 vascular injuries, including 112 arterial and 53 venous injuries, were repaired using a variety of techniques. In 136 patients undergoing operative intervention, there was no operative mortality and a 1.5% amputation rate. PMID- 4015371 TI - Free-floating iliofemoral thrombus. A risk of pulmonary embolism. AB - We retrospectively evaluated the risk of pulmonary embolism in hospitalized patients with venographically proved iliofemoral deep vein thrombosis (DVT). Venograms and clinical records of 78 patients with iliofemoral DVT were reviewed and the proximal intraluminal thrombus was characterized as free-floating (greater than 5-cm nonadherent segment) or occlusive (no free-floating elements). The incidence of pulmonary embolism confirmed by high-probability radioisotope ventilation-perfusion lung scanning within ten days following venography was 9% (7/78) and was associated with 60% (3/5) free-floating and 5.5% (4/73) occlusive phlebographic criteria (P less than .05). All patients who experienced pulmonary embolism were given therapeutic heparin treatment (partial thromboplastin time, more than twice the control value). The mean (+/- SD) time from the diagnosis of DVT to pulmonary embolism was 104 +/- 60 hours, and 120 +/- 71 hours for patients with free-floating and occlusive thrombi, respectively (P greater than .05). Patients with iliofemoral DVT that met free-floating criteria are at significant risk for pulmonary embolism, despite the administration of heparin. PMID- 4015372 TI - In situ femoropopliteal and infrapopliteal bypass. Two-year experience. AB - We describe 83 in situ femoropopliteal and infrapopliteal artery bypass grafts. The in situ technique involved the valve incision method using scissors, the valvulotome (Leather), and a modified valve cutter (Hall). Arteriovenous fistulae were detected intraoperatively by angiography and/or the Doppler method and ligated. The operative indications were rest pain, ulcer, and gangrene in 88% of cases, and claudication in 7.2%. The mean preoperative ankle pressure was 61.3 mm Hg and the ankle-brachial index was 0.43. The mean postoperative ankle pressure was 125.3 mm Hg and the ankle-brachial index was 0.97. The vein utilization rate was 96%. One-year patency for popliteal anastomoses was 85.7%, for peroneal anastomoses it was 100%, and for infrapopliteal anastomoses it was 89.6%. The data suggest that the practicing vascular surgeon can adopt the in situ technique and can expect high graft patency rates even in limb salvage situations with poor distal outflow. PMID- 4015373 TI - Results of aortic grafting in occlusive vs aneurysmal disease. AB - Recent demographic and biochemical studies have suggested that there may be significant differences in the population of patients undergoing reconstruction for an aortic aneurysm (AA) or atherosclerotic occlusive disease (OCC) of the abdominal aorta. The purpose of this retrospective study was to compare the results of aortic surgery in these different patient groups. One hundred three patients undergoing aortic grafting were reviewed. Twenty-four patients underwent reconstruction for OCC, 65 selectively for asymptomatic aneurysms (EAA), and 14 for ruptured aortic aneurysms (RAA). The mean age for OCC patients (54 years) was significantly lower than that for EAA (68 years) or RAA patients (71 years). Patients with AA were predominantly male (92%) compared with those with OCC (62%). Despite the age and sex differences, there were no significant differences between the groups in the incidence of cardiac disease, hypertension, smoking history, diabetes mellitus, or renal or pulmonary disease. In addition, there were no significant intraoperative differences in terms of operative and clamp times, fluid administration, urine output, hypotension, or subsequent postoperative morbidity and mortality. We conclude that despite AA and OCC patients being demographically distinct, there is essentially no difference in elective aortic bifurcation graft surgery between these two populations. PMID- 4015374 TI - Intra-abdominal abscess unassociated with prior operation. AB - During the past five years, 65 patients were treated for intra-abdominal abscesses unassociated with prior operation. Radiologic tests proved quite accurate in confirming the diagnosis. Abdominal x-ray films were abnormal in 25 (57%) of 44 patients, as were ultrasonograms in 33 (89%) of 37 patients, computed tomography scans in 13 (100%) of 13 patients, and gallium scans in five (100%) of five patients. Celiotomy was performed in each patient with both abscess drainage and the appropriate management of the diseased organ. Seven patients (10.8%) died, and in five death was due to uncontrolled sepsis. Duration of hospitalization averaged 23 days (seven days preoperatively and 16 days postoperatively). Twenty-two (34%) of 65 patients had an incorrect preoperative diagnosis leading to prolonged antibiotic treatment and delay in operation. The mortality was significant in seven (10.8%) of 65 patients, unrelated to the type of operative drainage (Penrose v sump) but clearly related to uncontrolled intra abdominal sepsis. A heightened suspicion of this problem should allow for an earlier diagnosis and an improved outcome. Prompt abdominal reexploration is indicated in those patients manifesting continued evidence of sepsis or organ failure. PMID- 4015375 TI - Review of gunshot wounds in Dayton, Ohio. Demographics, anatomic areas, results, and costs. AB - A retrospective review of 210 admissions for gunshot wounds was performed to evaluate the frequency that various anatomic areas were injured, complication rates, results of treatment, and costs. Seventy-two percent of patients had a single anatomic site involved. The complication rate was 13% and the death rate was 10.9%. A good result was obtained in 72%, but 12.4% had long-term disabilities. The average length of stay was 11 days with an average cost of +5,682 per patient. Application of today's prospective payment under diagnosis related groups suggests this system of payment may adversely affect the delivery of trauma care in this country. PMID- 4015376 TI - A comparison of decision analysis and second opinions for surgical decisions. AB - Second opinions and decision analysis, a mathematical process the decision maker can use to represent and solve problems, were compared in hypothetical surgical situations. Fifty expert surgeons gave opinions and provided the information necessary to solve the problems by decision analyses. Each surgeon's opinion was randomly selected again as a second opinion. In six difficult cases, 59% of the individual opinions were correct when compared with previously determined answers. For two surgical second-opinion protocols, the accuracies were 54% and 60%. The accuracy of the decision analyses was 69%. Improvement from second opinion protocols can be predicted mathematically and is limited. Improvement from decision analysis is not limited by mathematical constraints. Decision analysis may be preferable to second opinions in verifying surgical decisions. PMID- 4015377 TI - Extraorbital sebaceous carcinoma. AB - Although sebaceous carcinoma constitutes 1% to 5.5% of all malignant neoplasms of the eyelid, less than 100 cases arising in extraorbital sites have been reported. We treated two cases of extraorbital sebaceous carcinoma arising in anatomic regions never previously reported, to our knowledge. These tumors occur generally in older patients and affect both sexes equally. No clinical features are characteristic of the tumor, but larger skin lesions should be approached with suspicion. Appropriate histopathologic identification is particularly important in the differential diagnosis. Radical surgery is the only effective treatment for this rare tumor, which can recur locally or produce lymph node and even distant metastases. PMID- 4015378 TI - Congenital anorectal malformations. Harbingers of sacrococcygeal teratomas. AB - Since 1973, seven infants treated at the University of Florida, Gainesville, for congenital anorectal anomalies have been found to have concomitant sacrococcygeal teratomas. As anorectal anomalies occur in approximately one in every 5,000 live births and sacrococcygeal teratomas are noted in one in every 40,000 live births, this presentation would suggest a prevalence that precludes a random association. The presence of significant anorectal strictures in these patients resulted in a delay in the diagnosis of the presacral teratomas. As the frequency of malignant change in sacrococcygeal teratomas has been documented to increase proportionately with age, early diagnosis and excision of these lesions is essential. Our experience with these children suggests that the presence of congenital anorectal malformations in infancy should raise the physician's index of suspicion for associated sacrococcygeal teratomas. PMID- 4015379 TI - Peer and/or peerless review. Some vagaries of the editorial process. PMID- 4015380 TI - Pancreatic cancer. Adjuvant combined radiation and chemotherapy following curative resection. AB - The efficacy of combined radiation and fluorouracil as adjuvant therapy for pancreatic cancer is suggested by a prospective randomized study conducted by the Gastrointestinal Tumor Study Group (GITSG). Twenty-two patients randomized to no adjuvant treatment and 21 to combined therapy were analyzed. Neither life threatening toxic reaction nor death due to toxic effect was encountered. The study was terminated prematurely because of an unacceptably low rate of accrual combined with the observation of increasingly large survival differences between the study arms. Median survival for the treatment group (20 months) was significantly longer than that observed for the control group (11 months). Four patients, three in the treated and one in the control group, have survived five years or longer following surgery. The extent of the tumor and initial performance status were significantly and independently related to survival. PMID- 4015381 TI - Irrigation management of sigmoid colostomy. AB - Questionnaires were sent to 270 patients who had undergone abdominoperineal resection and sigmoid colostomy at the Mayo Clinic, Rochester, Minn, during the ten years from 1972 to 1982; 223 patients returned their questionnaires with evaluable data. Sixty percent of the patients were continent with irrigation, and 22% were incontinent with irrigation. Eighteen percent had discontinued irrigation for various reasons. The proportion continent was higher in women, younger patients, and previously constipated patients. A poorly constructed colostomy may cause acute angle, parastoma hernia, stomal prolapse, or stenosis and thus be the cause of failure of irrigation. PMID- 4015382 TI - Growth changes in the thoracic aorta of the piglet following patch angioplasty. AB - Patch repair of the thoracic aorta using prosthetic graft material in neonates and infants has been advocated, but long-term results have not confirmed that the residual aorta grows. In this study five piglets had portions of aortic tissue excised, ranging from 38% to 72% of the aortic wall. Each pig underwent patch angioplasty repair of the thoracic aorta with prosthetic graft material. Piglets achieved full growth at approximately six months. Aortic catheterization and contrast angiography were done in each animal before it was killed. Growth and histologic study of the aorta was documented at postmortem examination. There were no blood pressure gradients at rest or with isoproterenol hydrochloride (Isuprel)-epinephrine challenge in four of the five piglets. In one animal that underwent a 72% resection of the aortic circumference, a 20-mm gradient was present at rest. It was concluded that the thoracic aorta in piglets will grow adequately to allow patch grafting of up to 70% of the aortic circumference. PMID- 4015383 TI - Management of acute postoperative thrombosis following carotid endarterectomy. AB - We reviewed 326 carotid endarterectomies performed from 1960 through 1981 and encountered five instances of acute postoperative thrombosis. Clinical decompensation occurs with the acute onset of severe neurologic deficits, most characteristically dense hemiplegias contralateral to the side that has been operated on. These deficits developed between two and 72 hours postoperatively. Prompt reoperation with thrombectomy and reestablishment of carotid flow within two hours from the onset of the neurologic deficit was performed on four patients with complete resolution of the deficits in three patients. The fourth patient recovered from a severe hemiplegia but retained a slight residual weakness of the hand. The one patient whose condition did not improve underwent thrombectomy more than 24 hours after the onset of her deficit. Time-consuming diagnostic procedures are not warranted as the success of reoperation depends on rapid reestablishment of cerebral flow. PMID- 4015384 TI - Regional blood flow and water content of the obstructed small intestine. AB - The effects of small-bowel obstruction on the regional distribution of blood flow and water content were studied in a new chronic dog model. Nonstrangulative obstruction was induced 40 cm proximal to the canine ileocolic valve. Blood flow was measured with 15-micron microspheres and hemodynamic and respiratory values were recorded before (experimental phase I) and five days after (experimental phase II) the induction of the obstruction. Two separate control groups of dogs were studied: baseline controls and sham-operative groups (phases I and II). Hemodynamic and respiratory values were stable in both phases in all groups. A comparison of sham phase-II data with the experimental phase-II data in the 120 cm segment of bowel proximal to the site of obstruction showed an 85% increase in blood flow (range, 49% to 106%); for the 280 cm of bowel proximal to the site of obstruction, there was a 6% increase in water content (range, 5% to 9%), and a 39% decrease in dry bowel weight (range, 34% to 46%). These findings help illustrate the pathophysiologic characteristics of microvascular changes in bowel obstruction, which are likely to have particular clinical significance for patients with cardiopulmonary diseases. PMID- 4015385 TI - In situ distal saphenous vein bypass using the intraluminal valve-disruption technique. AB - In the last few years there has been a resurgence of interest in in situ saphenous vein bypass for lower extremity revascularization because of improved patency rates. We performed 28 in situ bypass operations in 26 patients with threatened limbs using the intraluminal Hall valve disrupter. Seventy-five percent of these bypasses were to tibial vessels and had a 93% early patency rate. Three late failures were salvaged before thrombosis of the bypass, resulting in a cumulative patency rate of 93% with a mean follow-up of 17 months. In situ saphenous vein bypass has become our procedure of choice for distal reconstruction in severely ischemic limbs because of improved long-term patency compared with reversed-saphenous vein bypass. PMID- 4015386 TI - 2,3-Dihydroxybenzoic acid. Effect on mortality rate in a septic rat model. AB - Neutrophil-derived oxygen-free radicals may play a role in organ dysfunction associated with generalized sepsis. A rat model was used to test the effects of two free radical scavengers, dimethyl sulfoxide (DMSO) and 2,3-dihydroxybenzoic acid (2,3-DHB), on mortality from intra-abdominal sepsis produced by cecal ligation and perforation. Being an iron-chelating agent, 2,3-DHB may have an additional bacteriostatic effect. Therapeutic regimens included no treatment; gentamicin sulfate (2 mg given intraperitoneally [IP] every eight hours); DMSO (2 g/24 hr given IP every eight hours in divided doses); 2,3-DHB (35 mg/kg given IP every eight hours); and combinations of gentamicin with each free radical scavenger. No statistically significant improvement in survival was obtained by therapeutic intervention with gentamicin alone, DMSO alone, 2,3-DHB alone, or gentamicin in combination with DMSO. When used in combination with gentamicin, 2,3-DHB yielded a statistically significant improvement in survival when compared with gentamicin alone or with no treatment. These results show that 2,3-DHB when used in combination with gentamicin has a beneficial effect on mortality following intra-abdominal sepsis in this model. PMID- 4015387 TI - The effect of vitamin E on experimentally induced peritoneal adhesions in mice. AB - Previous studies in our laboratory demonstrated that dietary supplementation with vitamin A enhances peritoneal adhesion formation in mice. Other researchers have shown that vitamin E antagonizes some effects of vitamin A in various systems, eg, wound healing. We investigated our hypothesis that dietary supplementation with vitamin E would decrease peritoneal adhesion formation. Adult mice were divided into the following groups: group 1, which ate a standard chow containing 65 IU of vitamin E per kilogram diet (twice the National Research Council's recommended daily allowance for normal mice); and group 2, which ate the same chow supplemented with vitamin E at 300 IU/kg diet (a nontoxic level). Following peritoneal ligation, all mice were killed on the tenth postoperative day and their peritoneal cavities examined for the presence and extent of adhesions. There was a statistically significant decrease in the incidence and degree of adhesions in the vitamin E-supplemented animals; these data supported our hypothesis. PMID- 4015388 TI - Colostomy wound closure. AB - The management of the wound at the time of colostomy closure has been controversial, and wound infection is a frequently cited complication of this procedure. We have conducted a prospective randomized study of colostomy wound closure in 105 patients with three study groups: (1) primary closure (n = 38); (2) primary closure with subcutaneous drains (n = 29); and (3) delayed primary closure (n = 38). All patients had mechanical bowel preparation with whole gut lavage as well as oral neomycin sulfate/erythromycin estolate and perioperative parenteral cefazolin sodium (Ancef). Five wound infections (4.8%) occurred. Three infections were in the delayed primary closure group and one infection in each of the other two study groups. No statistical difference in wound infection was demonstrated. On the basis of the findings in this study, we would not recommend delayed primary closure for the management of colostomy closure wounds when careful mechanical and antibiotic preparation has been utilized. PMID- 4015389 TI - Inguinal hernias in premature infants operated on before discharge from the neonatal intensive care unit. AB - Sixteen premature infants were operated on during the two-year period from 1981 through 1982 for inguinal hernia prior to discharge from the hospital. There were no complications from the hernias before surgery and during administration of anesthesia and postoperative recovery, and no recurrences, would infections, or testicular atrophy was noted in long-term follow-up. In contrast to a controlled group of 11 full-term patients of this same age who were operated on as outpatients, the operating room time, operation time, and time in the recovery room were significantly increased for the premature infants. This resulted in a 22% increase in cost for the correction of the premature inguinal hernias. Analysis of the factors in repair of these hernias indicates that this increased cost will have to be accepted as part of the care of premature infants in neonatal intensive care units. PMID- 4015390 TI - The surgical implications of herniation of the urinary bladder. AB - The urinary bladder is often involved in an inguinal hernia, but herniation of the entire bladder into the scrotum is rare. As many as 4% of inguinal hernias may involve the bladder, usually in the form of a sliding hernia. Most urinary bladder herniations are diagnosed at the time of inguinal herniorrhaphy, and are therefore most commonly repaired through an inguinal incision. If the diagnosis requires amendment, alternative surgical approaches are available. We studied two patients with massive inguinoscrotal herniation of the urinary bladder, commonly referred to as "scrotal cystocele." We reviewed the literature, incidence, causes, diagnosis, and surgical consideration of herniation of the urinary bladder, and gave particular attention to the interrelationship of bladder herniations with inguinal hernias. PMID- 4015391 TI - Isolated traumatic aortic valvular insufficiency with rapid pulmonary deterioration. Report of two cases. AB - Blunt trauma followed by aortic valvular insufficiency occurs rarely. Valve replacement or repair has most often taken place several months or years after injury; only a few cases have been reported of acute operative intervention performed within a few days after injury. However, we herein report two cases of isolated aortic valvular trauma in young men, in whom fulminant pulmonary edema ensued so rapidly that urgent aortic valve replacement was necessitated within hours after injury. PMID- 4015392 TI - Biomonitoring of aniline and nitrobenzene. Hemoglobin binding in rats and analysis of adducts. AB - Covalent binding to hemoglobin was studied to further substantiate the proposal that it may be used for biomonitoring N-substituted aryl compounds. (14C)-Labeled acetanilide and nitrobenzene were orally administered to female Wistar rats and binding indices [Binding(mmol/mol Hb)/Dose(mmol/kg)] determined; these were 12 +/ 1 and 73 +/- 10, respectively. After mild acidic or alkaline hydrolysis, 90% of the bound material was released and identified as aniline by radio thin layer chromatography. This supports the hypothesis that nitroso aryl derivatives, common intermediates in the metabolism of N-substituted aryl compounds, react with SH-groups of hemoglobin to yield sulfinic acid amides. Aniline was furthermore identified and quantified by capillary gas chromatography, using hemoglobin from animals treated with unlabeled aniline and nitrobenzene. Binding indices in this case were 30 +/- 3 and 85 +/- 19, respectively. With this method human blood samples may also be analysed. Although nitrobenzene is known to produce less methemoglobin than aniline, hemoglobin binding is higher. This indicates that hemoglobin binding may be a better index of body burden than methemoglobin levels in biomonitoring N-substituted aryl compounds. PMID- 4015393 TI - Absence of lipid peroxidation as determined by ethane exhalation in rats treated with 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD). AB - The exhalation of ethane is widely used as an indicator of in vivo lipid peroxidation. To test the hypothesis that lipid peroxidative events are involved in the toxicity of 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD), we administered a lethal dose of TCDD (60 micrograms/kg), IP to male Sprague-Dawley rats (160-180 g) and measured by gas chromatography the exhalation of ethane into the atmosphere of a closed all-glass exposure chamber. TCDD-treated rats exhaled only slightly more ethane than control rats at a single time point 7 days following TCDD administration. Since the exhalation of ethane is the net result of the endogenous production of the gas and its metabolic degradation, the latter was quantified by measuring the clearance of exogenous ethane (initial concentration = 100 ppm) introduced to the atmosphere of the exposure chamber. The clearance of ethane in TCDD-treated rats was markedly decreased, reaching a minimum 7 days following TCDD treatment. Apparently, the slight increase in exhaled ethane was due to an inhibition of ethane metabolism caused by TCDD. However, rats obviously intoxicated and having lost considerable body weight might be impaired in their ability to transport ethane. To bypass this problem we injected ethane (0.2 ml) directly into the rats IP. Here also the metabolic clearance in TCDD-treated rats was diminished. In a further experiment, rats treated with dithiocarb at a dose where ethane metabolism was totally inhibited exhaled more ethane than did TCDD treated rats.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4015394 TI - Covalent binding and glutathione depletion in the rat following niridazole (ambilhar) pretreatment. AB - In vivo and in vitro studies with rats have shown that (14C) niridazole (Ambilhar) binds covalently to tissue proteins, but not to nucleic acids. In the in vitro experiments, binding required the presence of NADPH in the incubation medium, suggesting the production of an active metabolite via a cytochrome P-450 mediated reaction. Niridazole also caused significant dose-dependent decreases in liver and kidney glutathione levels, even though it had no apparent effect on blood glutathione. Alteration of tissue glutathione availability by pretreatment with chloracetamide or cysteine respectively either increased or decreased the NADPH-dependent covalent binding. Pretreatment with phenobarbital, 3 methylcholanthrene or cobaltous chloride, which change the rate of metabolism of (14C) niridazole, similarly altered the extent of protein binding. It is shown that the decrease in tissue glutathione concentration is not due to an effect of the drug on the activities of either glucose-6-phosphate dehydrogenase or glutathione-S-transferases. However, there is a significant reduction in glutathione reductase activity in all the tissues studied. The possible relationships between the results obtained and the cytotoxic effects of niridazole have been discussed. PMID- 4015396 TI - Fast uptake kinetics in vitro of 51Cr (VI) by red blood cells of man and rat. AB - Fast transport kinetics of 51Cr (VI) into red blood cells (RBCs) in vitro were studied. No significant species differences were found between RBCs of man and rat. The uptake of 51Cr (VI) by RBCs in whole blood was composed of two different first order processes of different velocities (apparent t 1/2 of 22.7 s and 10.4 min for man and 6.9 s and 10.1 min for rat, respectively). However, even after longer time periods a fixed portion of approximately 15% of the administered dose remained in the plasma and did not penetrate into RBCs Over the entire concentration range studied (10 microM-50 mM), the fast initial uptake followed Michaelis-Menten kinetics. The maximal capacity of this Cr(VI) transport into RBCs of man and rat was 3.1 X 10(8) CrO4(2-) ions X cell-1 X min-1 and 2.5 X 10(8) CrO4(-2) ions X cell-1 X min-1, respectively. It is likely that Cr(VI) is transported into RBCs via a physiological anion carrier ("band-3-protein"). PMID- 4015395 TI - Early biochemical and morphological changes of the rat adrenal medulla induced by xylitol. AB - Long-term administration of high doses of xylitol and other polyols in rats has been associated with an increase in adrenal medullary hyperplasia and neoplasia. In order to exclude age-related factors and to differentiate between unspecific stress reactions and direct effects of the compound administered, a model was developed for quantifying early adrenomedullary responses. Male SD rats were fed xylitol (10% or 20% in the diet) for 2 and 8 weeks, and early biochemical changes were correlated with a stereological analysis of the adrenal medulla. At first, the in vivo rate of catecholamine (CA) biosynthesis was slightly decreased (at 2 weeks). This was followed by an increase in dopamine-beta-hydroxylase (DBH) activity (at 8 weeks). By that time, the total chromaffin cell volume had increased and the number of chromaffin cells per reference volume had decreased in a dose-dependent way. The total number of chromaffin cells per adrenal gland showed a distinct tendency towards an increase. Adrenal epinephrine and norepinephrine contents were not altered, and both tyrosine hydroxylase and phenylethanolamine-N-methyltransferase activities remained unchanged. These data suggest that continued xylitol administration evoked an inhibitory effect on CA synthesis that, together with stimulation of the adrenal medulla brought about by the compound, resulted in compensatory medullary hypertrophy and hyperplasia. PMID- 4015397 TI - Lead and cadmium in breast milk. Higher levels in urban vs rural mothers during the first 3 months of lactation. AB - Breast milk from 10 women each from the city of Hamburg and from a rural area was analyzed by atomic absorption spectrometry for contamination with lead and cadmium. Samples were examined at regular intervals for 3 months after birth. On day 5 a diurnal profile was analyzed; on the other days milk was taken before and after the morning feed. Daily permissible intake (DPI) for lead is 5 micrograms/kg/day for children; the DPI for cadmium has as yet been determined only for adults as 400-500 micrograms/week, equivalent to about 1 microgram/kg/day (WHO 1972). For breast milk as the main source of nutrition in infants, this study shows values of 9.1 +/- 2.5 (SD) microgram/l for lead in the rural population, with a tendency to decrease towards the end of lactation. Urban mothers had 13.3 +/- 5.5 (SD) microgram/l, with a tendency to increase. This difference was significant only on day 45. Mean cadmium content in rural mothers was 17.3 +/- 4.9 micrograms/l, with much higher values in the colostrum and a decrease after 15 days. Urban mothers had 24.6 +/- 7.3 micrograms/l, again with high colostrum values and a subsequent decrease. These latter values are not significantly different. Calculated daily intake according to these values is presented, based on 840 ml breast milk for a 5.5 kg infant per day. Rural infants ingested 0.9-1.3 micrograms/kg/day of lead, and in the city 1.5-2.3 micrograms/kg/day. Cadmium intake in rural infants amounted from 1.2-1.8 micrograms/kg/day; in Hamburg it was 1.6-2.2 micrograms/kg/day.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4015398 TI - Phthalates and organophosphorus compounds as cholinesterase inhibitors in fractions of industrial hexane impurities. AB - Cholinesterase (ChE) inhibitors have been described in the distillation residue of hexane and other industrial solvents. The residue of a commercial hexane has been fractionated by preparative chromatography. The anticholinesterase (antiChE) activity was isolated in two fractions (F-5, F-7) which contained only 0.61 and 0.16% respectively of the original dry weight hexane residue. In the former fraction, reversible and irreversible progressive inhibition was observed, and organophosphorus compounds (OPs) were detected colorimetrically and by gas chromatography. This fraction was subfractionated in a second chromatographic step. One subfraction containing the highest antiChE activity and 88% phosphorus of F-5 was isolated. In this subfraction triphenylphosphate and other not definitely identified OP compounds were detected by gas chromatography/mass spectrometry, together with several adipates and phthalates, including di-n butylphthalate. This phthalate could explain the reversible inhibition of ChE by the hexane residue, and triphenylphosphate and the unidentified OP the irreversible inhibition. A possible toxicological role of these impurities is discussed in relation to occupational neuropathies by exposure to solvents. PMID- 4015399 TI - Some behavioral effects of early styrene intoxication in experimental animals. AB - Male albino rats were administered styrene in groundnut oil, PO at doses of 100 mg and 200 mg/kg body weight daily for 14 consecutive days. No neurological deficit was observed in any animal during the course of the experiment. Mean % avoidance response (learning) for each treated group, from day 1 to day 4 of conditioned avoidance response training, revealed a general increase. Styrene significantly increased the % avoidance response at both doses as compared to controls, although no definite dose-response relationship was evident. No significant difference was noted in the spontaneous locomotor activity and regional brain catecholamine levels, between controls and treated rats of either dose. Serotonin levels in hippocampus, hypothalamus, and mid-brain were significantly raised at the higher dose of styrene. Therefore, elevated serotonin levels in these brain regions may account for styrene-induced learning. PMID- 4015400 TI - Acute thallium intoxication: kinetic study of the relative efficacy of several antidotal treatments in rats. AB - Rats were administered a sublethal dose of thallium (12.35 mg/kg as aqueous thallous sulfate, Tl2SO4, equivalent to 10 mg Tl+/kg per os) on day 0. Urine and feces were collected separately every day for 8 days and analyzed by atomic absorption spectroscopy. Based on information in the literature, five antidotal treatments (dithizone, activated charcoal, furosemide, Prussian Blue, and a combination of Prussian Blue and furosemide) were compared with controls for their efficacy in reducing the total thallium body load. In the control group (C,n = 10) of an approximate administered dose of 2 mg, after 8 days 411 micrograms (21%) had been eliminated in the urine and 641 micrograms (32%) in the feces, making a total of 1,052 micrograms (53%). In the treated groups the effects were very significant and in accord with the mode of action of the antidotes: furosemide (a diuretic) only enhanced urinary elimination; activated charcoal and Prussian Blue (unabsorbed adsorbents) only increased fecal elimination; dithizone increased only urinary elimination, whereas combined treatment with Prussian Blue and furosemide increased elimination by both routes. At the end of 8 days the control group had only eliminated 53% of the dose; this was increased to 99% by dithizone, 93% by activated charcoal, 64% by furosemide, 82% by Prussian Blue and 92% by combining furosemide and Prussian Blue. In view of the inherent toxicity of dithizone, it is suggested that treatment with a combination of Prussian Blue-furosemide or with activated charcoal should be adequate.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4015402 TI - An evaluation of the efficacy of charcoal haemoperfusion in the treatment of three cases of acute thallium poisoning. AB - The efficacy of intermittent charcoal haemoperfusion in combination with forced diuresis and Prussian blue therapy was evaluated in three cases of thallium poisoning. At a blood flow of 300 ml/min the average blood clearance values obtained with haemoperfusion were 72 +/- 11 ml/min (mean +/- SD) at a starting blood concentration above 2 mg/l and 120 +/- 23 ml/min (mean +/- SD) below this blood level. As a result of the combined intensive treatment, the thallium half lives in blood observed during the period monitored were only 25-41 h. Removal of thallium by haemoperfusion is faster per unit of time than simultaneous excretion by forced diuresis. When forced diuresis was combined with intermittent (4-20 h intervals) haemoperfusion therapy, the total elimination by each technique was about equivalent over the period of combined treatment. Saturation of the Adsorba 300 C columns occurred during treatment. As a result, the clearance obtained did decrease to half the initial value in 2-3 h. As this decrease in efficacy is related to the blood concentration, haemoperfusion is more efficient at lower blood concentrations. This is in contradistinction to forced diuresis, of which the excretion is proportional to the blood concentration. PMID- 4015401 TI - Covalent binding of BP-metabolites to DNA of cultured human hair follicle keratinocytes. AB - Primary cultures of human hair follicle keratinocytes were established by using a basement membrane-like growth substrate, the bovine eye lens capsule. A method was adapted for the isolation of 3H-benzo(a)pyrene (BP)-modified DNA from the cellular outgrowth of only one hair follicle (approximately 2 X 10(5) cells). In a routine procedure hair follicle keratinocytes were incubated with 0.5 microM 3H BP for 24 h. The purified DNA was subjected to enzymic hydrolysis and the adducts were analyzed by Sephadex LH-20 column chromatography followed by HPLC. Only one major adduct, which represented 60-80% of the total radioactivity which can be confined to modified nucleosides in the LH-20 chromatograph, could be identified. This adduct co-chromatographed with the marker adducts resulting from the trans addition of the N-2-amino group of guanine to the 10-position of (+/-)-7 beta,8 alpha-dihydroxy-9 alpha,10 alpha-epoxy-7,8,9,10-tetrahydrobenzo(a)pyrene. Co incubation with 7,8-benzoflavone (0.3 microM), an inhibitor of cytochrome P-448, and with 1,1,1-trichloropropene-2,3-oxide (0.2 microM), an inhibitor of epoxide hydrolase, resulted in a marked inhibitory effect (15% of the control binding) and a large increase (300% of the control value) in BP-DNA binding respectively. Induction of aryl hydrocarbon hydroxylase activity in the cultures with 5,6 benzoflavone (10 microM) or benz(a)anthracene (10 microM) caused a decrease (75 and 46% of the control value respectively) in BP-DNA binding.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4015403 TI - Parathion and gastrointestinal transit in the rat. AB - The possibility of in vivo or post-mortem acceleration of gastrointestinal transit was investigated in the rat after sublethal or lethal doses of the insecticide parathion. Parathion did not change gastrointestinal transit time before or after death in the poisoned rat. PMID- 4015404 TI - Dexamethasone decreases lethality of rats in acute poisoning with T-2 toxin. AB - T-2 toxin, a major trichothecene mycotoxin, was administered intravenously to rats. At a dose of 0.75 mg/kg two thirds of the animals died. In animals that received dexamethasone (1.6 mg/kg IV) either 30 min before or 1 h after the toxin, there was a more than fourfold reduction in lethality rate. Dexamethasone injected 3 h after the toxin was less effective. At a lethal dose of T-2 toxin (1 mg/kg IV) pretreatment with dexamethasone only delayed death, whereas lethality rate was barely affected (9/10 vs 10/10 in controls). Dexamethasone markedly reduced the incidence of lung edema and diarrhea. The incidence of hemorrhages, however, was not reduced by dexamethasone. Gastrointestinal bleeding was even more frequent in treated rats than in controls. PMID- 4015405 TI - Stability of infectious influenza A viruses to treatment at low pH and heating. AB - We have measured the infectivity of influenza A virus strains grown either in embryonated eggs or in chick embryo cells in culture after treatment at low pH. At pH values at which hemolysis occurs there was an irreversible loss of infectivity. The threshold pH, at which the infectivity was lost, depended on the hemagglutinin subtype of the virus strain. All H5 and H7 strains tested were extremely labile at low pH. In contrast, all H3 strains were relatively stable, independent of the species from which the viruses were isolated. With several H1 viruses the hemagglutination (HA) activity was irreversibly lost at intermediate pH values causing inactivation of infectivity. Strains with noncleaved hemagglutinins were much more stable. These observations might explain why duck influenza viruses can easily survive in lake water and wet faeces, and multiply in the intestinal tract, where trypsin is present. There are also significant differences in heat stability exhibited by influenza A strains. In contrast to pH stability this is not a specific trait of the hemagglutinin, since it can be influenced by reassortment. There is no correlation between the stability of infectivity at low pH and heat. PMID- 4015406 TI - Dengue virus induced polypeptide synthesis. Brief report. AB - Dengue 2 virus polypeptide synthesis was investigated in BHK21 cells. Nine or ten virus induced polypeptides were identified, three of which are glycoproteins as demonstrated by tunicamycin treatment of infected cells. We performed pulse chase experiments, experiments with amino-acid analogs, protease inhibitors or pactamycin treatment of infected cells, to determine whether or not large polypeptide processing occurs. In some of these experiments a large polypeptide (P 130) was immunoprecipitated by an anti-dengue 2 serum. We observed a transfer of label between small molecular weight polypeptides which might be the result of restricted proteolytic cleavage. PMID- 4015407 TI - Heterogeneity among influenza H3N2 isolates recovered during an outbreak. Brief report. AB - Isolates of the H3N2 subtype recovered during an outbreak have been analyzed at the genomic and protein level. No reassortant genomes were detected. By T1 oligonucleotide fingerprinting of RNA segments coding for hemagglutinin (HA), nucleoprotein (NP), and neuraminidase (NA) two genotypes were found. PMID- 4015408 TI - Direct evidence for the anti-inflammatory effect of human interferon-alpha in CFLP mice. Brief report. AB - In CFLP mice, intravenously administered partially purified interferon-alpha (IFN alpha 2 X 10(6) mu/mg protein), prepared from human leukocytes, reduced carrageenan-induced paw swelling and produced slight irritation when injected into the footpad. Anti-human IFN-alpha serum abolished the anti-inflammatory effect but did not influence local phlogogenic activity. Highly purified human IFN-alpha (1.2 X 10(8) mu/mg protein) was also found to be anti-inflammatory after intravenous administration, and devoid of irritative effect at the injection site. These results suggest that human IFN-alpha possesses a direct inhibitory effect on acute inflammation in mice, and the irritation appearing at the site of its application might be due to some impurities being present in the partially purified preparations. PMID- 4015409 TI - Characterization of hemagglutinin variant strains of adenovirus 15 and 9. Brief report. AB - Five adenovirus 15/Hx and one Ad9/Hx strain with a common novel hemagglutinin were compared serologically and by DNA restriction analysis with six endonucleases with the related prototypes. The five Ad 15/Hx strains represented five different genome types. PMID- 4015410 TI - Growth of the Phlebovirus Toscana in a mosquito (Aedes pseudoscutellaris) cell line (AP-61): establishment of a persistent infection. AB - Toscana Virus, a sandfly-associated Phlebovirus, was adapted to grow in cultured Aedes pseudoscutellaris (AP-61) mosquito cell line. No evidence of virus growth was seen after primary infection of cell monolayers under maintenance conditions. On the contrary, persistent infections were established by subculturing infected cultures. Cytopathic effect was never observed. Significant titres of virus (10(3)-10(5) PFU/ml), as assayed in Vero cells at 37 degrees C, were released from persistent infected cells after several subcultures at 29 degrees C over a period of six months. The percentage of virus-producing cells in the persistently infected cultures varied from 0.003 to to 0.017 per cent, whereas from 10 to 50 per cent of cells were shown to retain viral antigens by immunofluorescence. The virus released from persistently infected cultures did not show changes in both plaque size and temperature sensitivity from the parental virus. The virus released from persistently infected cultures multiplied in AP-61 cell monolayers reaching relatively high titres (10(4) PFU/ml). PMID- 4015411 TI - [Connections between the posterolateral nucleus of the thalamus and the parietal and occipital areas of the cerebral hemispheres in the cat]. AB - A light optic and electron microscopic investigation on distribution of fibers from the thalamic posterolateral nucleus has been performed in the cat cerebral cortex. The fibers studied are revealed in the fields 7, 19 and 18. In the field 7 they are most numerous, comparatively seldom they are found in the field 19 and still more seldom--in the field 18. In the fields 7 and 19 identical peculiarities on distribution and termination of the fibers are noted: they spread across the whole cortex and end in all the layers with a predominant concentration in the layers III and IV. Most of the fibers make contacts on small dendritic branches and spines. In the field 18 the fibers are mainly limited by the medial layers and terminate predominantly on small, middle-sized dendritic branches, and comparatively rare--on the spines. PMID- 4015412 TI - [Connections between the structuro-spatial architectonics of the neural apparatus of the thyroid gland and its functional activity during cold adaptation]. AB - By means of the fluorescent-histochemical method for revealing monoamines in combination with morphometric analysis and radiologic testing, the thyroid gland activity has been estimated. The spatial characteristics of the perivascular and parafollicular adrenergic plexuses are closely interrelated in time with fluctuations of the specific thyroid function that accompanies the development of the organism's adaptation. Redistribution of the monoamines transport canals towards structures of the greatest functional strain results in an increased density of the parafollicular sympathetic neural apparatus which directly performs the adaptational-trophic influence on thyrocytes. This ensures the status of a moderate hyperactivity in the organ. PMID- 4015413 TI - [Myeloarchitectonics of the vagus nerve in man]. AB - In serial electively stained transversal sections of the vagus nerve trunk taken at the levels beginning from its exit out of the brain, up to terminal branches in the abdominal cavity (10 corpses of mature persons) myelin fibers of three classes have been counted. Along the course of the nerve trunk in the craniocaudal direction the total number of the myelin fibers decreases. Only about 10% of the initial amount of the myelin conductors revealed at the level of the intracranial part of the vagus nerve get into the abdominal cavity. Simultaneously, the ratio of the myelin fibers belonging to different classes changes: the part of the fine conductors increases, and that of the fibers having middle and large diameters decreases. The most important in the dynamics of the whole amount of myelin fibers and in the number of the conductors belonging to different classes at all the levels of the nerve trunk is the getting off the organs' branches with various functional specialization. PMID- 4015415 TI - [Structural features of the intrinsic venous bed of the human urinary bladder]. AB - The intraorganic veins of the human urinary bladder have been studied in a vast sectional material. The veins within the organ make an enormous multilayered plexus which is differently organized in various layers of its wall. Abundant anastomoses, multiplicated ways for outflow from every layer, manifested interactions between the venous plexuses are specific for the intraorganic venous bed of the urinary bladder. The structures for an active regulating the hemomicrocirculatory blood stream are widely presented in the urinary bladder. In its every tunic certain specific morpho-functional features for organization and adaptation of the intraorganic venous bed are revealed. PMID- 4015414 TI - [Constitutional and age-related properties of the aortic isthmus]. AB - By means of micro- and macropreparation and morphometry methods in 200 corpses of children and adult persons, it has been stated that skeletotopy and syntopy of the aortal isthmus depends on the constitution of the person. Certain objective criteria have been elaborated for surgical approaches to the aortal isthmus. In little children, during early and first childhood, anterolateral thoracotomy should be performed in the III intercostal space; in persons with brachymorphose type of constitution--left-sided thoracotomy in the IV intercostal space; in persons with transitional and long-narrow thorax--left-sided thoracotomy in the V intercostal space with resection of the V rib. PMID- 4015416 TI - [Microangiographic signs of blood vessel rearrangement during tumor growth]. AB - In the experiment performed in mice with a subcutaneously implanted sarcoma-37 on the chin, rearrangement of the blood vessels has been followed by means of micro roentgenography. In the process of the implanted tumour growth, the blood vessels undergo a profound functional-anatomical rearrangement, which develops, beginning from the first hours, in two ways: at the expense of the peripheral vessels rearrangement in the recepient and at the expense of real tumorous vessels development ensuaring vascular trophic of the tumour. PMID- 4015417 TI - [Stereologic analysis of the respiratory zone of the lungs of the laboratory rat and man during aging]. AB - By means of stereological analysis methods, lungs of mature and ageing laboratory rats and those of human beings at the age of 21-40, 41-60 and further have been studied. During the process of ageing the fraction of nonparenchymatous structures increases, while that of parenchyma decreases. Architectonics of acini is described: the volume of central passages increases and the volume of alveolar air decreases. The form of the alveoli approaches the spherical one. The area of the internal surface and the alveolar volume increase. The total number of the alveoli and the area of the respiratory lining decrease. The total number of the alveolar capillaries does not change, however, the density of their distribution grows small. The area and volume of a separate segment of the alveolar capillaries grow large. The age rearrangement of the respiratory zone morphologically differs from the changes that are observed at the obstructive emphysema. PMID- 4015418 TI - [Structure of the spleen of Papio hamadryas during ontogenesis]. AB - By means of morphometrical and histochemical methods serial topographic sections of the spleen have been studied in 23 Papio hamadryas of five age groups: fetuses, newborns, 1.5-2 years of age, mature and old animals. The peculiarities of morphogenesis and age histology of the monkey spleen have been followed and their similarity with changes of the organ in the human ontogenesis has been compared. Owing to the analysis of the structural components and the cellular composition relations, it is possible to conclude that in the fetuses the histological structure of the spleen is not completed, the maximal cytopoetic activity of the organ is observed in 1.5-2-year-old animals and involutionary changes begin in mature period. Possible functional peculiarities of the spleen are considered during various age periods. PMID- 4015419 TI - [Colony-forming ability of precursor cells of granulomonocytopoiesis in an agar bilayer system in healthy subjects]. AB - It is necessary to know growth characteristics of normal hemopoietic cells in order to estimate their clonogenic properties at different diseases of the blood system. Twelve healthy persons at the age of 27-49 years have been examined. Cellular aggregates have been counted on the 7th day. The aggregates containing more than 20 cells are considered as colonies, the aggregates containing 3-20 cells--as clusteres. The number of the aggregates is recounted as 1.10(5) nuclear cells. Among the colonies the overwhelming majority belong to neutrophilic ones, among the clusters this predominance is not so clearly manifested. The cells become mature up to the stab and segmental neutrophils and monocytes. Among the clusters, besides the neutrophilic aggregates, there is an essential part of the macrophagal ones. PMID- 4015420 TI - [Features of adaptive changes in the knee joints of fencers exposed to specialized loads]. AB - Sportsman-fencers (683 persons) of various qualification and types of fencing (sabre fencers, foil fencers, swordsmen) have been roentgenologically examined. Of them 97 have been examined for the second time in a year. For a comparison 204 persons nonsportsmen have been examined. Increased specialized loadings of chop push character, peculiar for fencing, accelerate processes of bone sinostosis and result in certain morphological changes in the components of the knee joint: the joint cartilage becomes thinner (as demonstrates the roentgenologically measured joint cleft), periostal osteogenesis on the surface of epiphyses, endothelial osteogenesis in the bone diaphyses become activated. PMID- 4015421 TI - [Dynamics of the ultrastructure of fibroblasts during pre- and postnatal development of the dermis in the rat according to electronic morphometry]. AB - Fibroblasts have been investigated in 18-day-old embryos, in newborns, in 2-week old and in 2-month-old rats of postnatal development. Comparison of fibroblasts population is specific for each stage. Average section area of the fibroblasts nucleus is progressively decreasing during ontogenesis. Average section area of cytoplasm reaches its maximum by the end of the second week of the life and then decreases sharply, and therefore the nucleus/cytoplasm ratio in the fibroblasts is minimal at the age of two weeks. The Golgi complex section area decreases significantly in mature animals as compared to the young ones. Summational extent of the granular endoplasmic reticulum membranes in the fibroblast section in the 2-week-old animals is 2.5 times as great as the corresponding parameters in the fetuses, newborns and mature animals. This parameter is greatly informative for determining the fibroblast type in accordance with its synthetic activity. PMID- 4015422 TI - [Device for raising cadavers out of baths]. PMID- 4015423 TI - [Modelling organs out of modelling clay as a practical exercise in anatomy]. PMID- 4015424 TI - [Histophysiologic microsystem as an element in the structural hierarchy of the body]. PMID- 4015425 TI - Automatic implantable cardioverter-defibrillator: a device for malignant ventricular arrhythmias and sudden death. PMID- 4015426 TI - Barrett's esophagus. PMID- 4015427 TI - Gonorrhea in medically indigent (AHCCCS) patients. PMID- 4015428 TI - Autopsie nouvelle. PMID- 4015429 TI - Mechanical ventilation: weaning criteria and methods. PMID- 4015430 TI - Early experience with an implantable reservoir for intravenous chemotherapy. PMID- 4015431 TI - Air embolism during neurosurgery in children. PMID- 4015432 TI - Herpes simplex virus (type 1) encephalitis: report of a case treated with acyclovir. PMID- 4015433 TI - Immunosuppression with corticosteroids and thymectomy in myasthenia gravis: an evaluation of immediate and short term results in 20 patients. AB - A comparative study was conducted on two groups of patients with the generalized severe form of myasthenia gravis. The first group of 20 patients received oral daily doses of 60-100 mg of prednisone prior to thymectomy. The control group of 20 were submitted to surgery without prior corticosteroid treatment. The study included statistical analysis of the clinical results and surgical complications for both groups. The authors concluded that the use of steroids preoperatively is beneficial. PMID- 4015434 TI - [Detection by the immunoenzymatic test ELISA of IgM anti-Cysticercus cellulosae antibodies in the cerebrospinal fluid in neurocysticercosis]. AB - IgM antibodies against Cysticercus cellulosae in the cerebrospinal fluid (CSF) was demonstrated by ELISA immunoenzymatic assay in neurocysticercosis. CSF samples of 41 patients were analyzed for this purpose. Diagnosis was neurocysticercosis in 26 and neurosyphilis in 5; abnormalities were not registered in the other 10 cases. Neurosyphilis samples and no-abnormalities samples were considered as control groups. ELISA IgM assay for cysticercosis was negative in all CSF samples of control groups and it was positive in 12 of the 26 CSF samples of the neurocysticercosis group (46.2%). Titers ranged from 4 till 32. Positive results were no more obtained after previous treatment of CSF samples by 2-mercaptoethanol. ELISA IgM and IgG titers were compared. IgM titers wee higher than IgG titers in two cases. Results obtained were compared to those found through complement fixation, immunofluorescence and hemagglutination tests for the diagnosis of neurocysticercosis. PMID- 4015435 TI - [Neurocryptococosis and immunosuppression: experimental model in mice]. AB - In order to accomplish a model for immunosuppression in experimental conditions two lots of 50 young mice were divided into groups of 10, and submitted to dexamethasone ingestion. Two experiments were considered in the study. In the first experiment conditions for immunosuppression were established in 50 mice, by per os supply of several concentrations of dexamethasone in the water given for normal daily intake ad libitum. Criteria of immunosuppression considered include: hair standing on end; leukopenia by decrease of lymphocyte population; spleen atrophy in relation to controls, with severe hypoplasy of all lymphoid structures. In the second experiment another lot of 50 mice in similar conditions established for the first experiment and concerning the immunosuppression were submitted to intraperitoneal inoculation of near 10(6) Cryptococcus neoformans. Culture suspensions of cryptococci isolated from cerebrospinal fluid samples of human neurocryptococcosis cases were used for this purpose. Although fungi could be recognized in lungs, liver and spleen from every mice inoculated, only those with central nervous system involvement (near by an half of all) died. The discussion included considerations about the role of the blood-brain barrier function in the findings registered. PMID- 4015436 TI - [Transient global amnesia: study of 26 cases]. AB - The clinical picture and investigation of 26 patients (16 males and 10 females) with diagnosis of transient global amnesia (TGA) are reported. Age ranged from 51 to 78 years at the time of TGA, which occurred mor often between 60 and 70 year old people. Three patients presented more than one episode (3, 4 and 5). Precipitating factors were identified in 8 cases (emotional stress in 7 and physical exercise in 1). Risk factors for cerebrovascular disease were found in 13 cases, mainly hypertension (9 cases) and diabetes (3 cases). EEG was normal in 20 cases and disclosed diffuse delta waves in 2, temporal delta waves in 1 and temporal theta waves in another patient. CAT scan showed no abnormalities in 3 cases and ischemia in the vertebro-basilar system in another 2. Brain angiography was normal in 1 case and showed abnormalities in the vertebro-basilar system arteries in 3. During the follow-up period, which ranged from 1 to 84 months, no neurologic deterioration was seen. The role of risk factors for vascular diseases, epilepsy and migraine in the development of TGA is discussed. PMID- 4015437 TI - [Infantile neuroaxonal dystrophy: diagnosis during life by biopsy of the conjunctiva]. AB - Three cases of infantile neuroaxonal dystrophy diagnosed by conjunctival biopsy are reported. Some axons of the conjunctival nerves showed aggregates of tubular and membranous structures identical to the spheroids of the CNS. The visualization of these structures is the only diagnostic tool in this disease of unknown metabolic basis. Conjunctival biopsy which is ease to perform is the preferential technique for the diagnosis of this disease. Clinically, the intense hypotonia with pyramidal tract signs, the absence of seizures, the cerebellar atrophy observed at the computerized tomography suggest strongly the diagnosis of infantile neuroaxonal dystrophy. PMID- 4015438 TI - [Neurocysticercosis in the Southeast of Bahia: apropos of 4 cases]. AB - Report of four cases of neurocysticercosis observed in the Southeast of Bahia. This region is situated in the Northeast of brazil. The report is justified by the low incidence of the disease in this region of the country according to previous studies. Considerations are made on clinical forms observed, diagnosis and regional characteristics of human infestation. Public health rules considering the disease to be adopted in the region are discussed. The importance to consider neurocysticercosis among possible causes of headache and epilepsy in this region is emphasized. PMID- 4015439 TI - [Isodense intracranial hematomas: study of 5 cases]. AB - The authors report 5 cases of isodense intracranial hematomas identified by computerized tomography and confirmed by angiography and surgical procedures. Radiological aspects are discussed and tomographic signals are emphasized. PMID- 4015440 TI - [Imotivated laughter: report of 3 cases]. AB - The authors present three cases where the involuntary, imotivated laughter was a distinct finding. The first patient was a 29-year-old engineer, who had had several bursts of neurologic deficits, either sensitive or motor, which recovered almost completely and was diagnosed as suffering from multiple sclerosis. During and after one of the episodes he presented involuntary laughter and has been like this since then, albeit in much less extension. The second patient was a 35-year old housewife, who presented several episodes of brain infarction in both hemispheres which were considered as being the result of arteritis. No specific collagen disease was found. The CAT scan showed several hypodense areas in both hemispheres. The third patient was a 52-year-old man of Japanese ancestry who presented three years ago a sudden ischemic stroke with difficulty in the speech and left sided weakness, followed by bursts of imotivated laughter, which persisted since then. Subsequently he had another stroke. He is hypertensive and diabetic. The authors searched the literature for the different causes of involuntary laughter. The occurrence in multiple sclerosis, although reported by several authors is by no means a common finding. In the literature available no case of cerebral arteritis with involuntary laughter could be found. The pathophysiology of this rare symptom was discussed. PMID- 4015441 TI - [Neurocutaneous melanosis: autopsy study of a case]. AB - The clinical, radiological and autopsy features of a 5-month-old child with neurocutaneous melanosis are described. The patient had multiple disseminated benign cutaneous nevi. The pneumoencephalogram showed non-obstructive hydrocephalus. The patient died at the third day of hospitalization and autopsy was performed. A mild hydrocephalus and melanic specks in cerebellum and in the brainstem were disclosed. PMID- 4015442 TI - [Familial myasthenia gravis: report of 2 brothers]. AB - The familial form of myasthenia gravis is a relatively rare condition, occurring in about 3.4 per cent of myasthenic patients. Two familial cases with ocular myasthenia gravis are reported. They had a third brother who died probably with the same disease. Their parents are cousins. The authors made a brief approach of genetic, clinical, statistical and therapeutic aspects of the disease. PMID- 4015443 TI - [Jactatio capitis nocturnus: report of a case in an adult]. AB - A case of an adult female patient with jactatio capitis nocturnus evaluated in a sleep disorders center is reported. the unusual characteristics included symptoms initiating in early childhood and becoming more frequent with age, specifically observed during REM sleep. The occurrence in a 2-year-old son indicates the familial aspects of this syndrome. PMID- 4015444 TI - [Intracranial arachnoid cyst associated with subdural hygroma: report of a case]. AB - A case of a 10-year-old boy with a congenital arachnoid cyst in the right middle cranial fossa is reported. The symptoms were precipitated by head injury of moderate intensity, occurred some days before the beginning of the clinical picture. The computerized tomography has demonstrated the existence of a simultaneous right fronto-parietal subdural hygroma that was responsible for the intracranial hypertension syndrome. The influence of the cyst in the hygroma formation has been suggested. The mechanisms of growth, the etiology, clinical aspects, the diagnostics and the surgical treatment of the arachnoid cysts are discussed. PMID- 4015446 TI - What are the ethical and social implications of artificial organs? PMID- 4015445 TI - [Hemifacial spasm: report of a case]. AB - The author reports a case of a 28-year-old white girl who presented typical clonic spasm on the left side of the face without previous disorder of the facial nerve. No etiology could be determined. The treatment with carbamazepine has showed a very good response. PMID- 4015447 TI - Use of artificial pancreas and portable insulin infusion pumps in diabetes therapy: past, present, and future. AB - The development of the artificial pancreas (AP) was an important contribution to modern diabetology. The practical and theoretical findings obtained by its application in type I diabetic patients gave rise to new forms of treatment, i.e., portable insulin pumps and intensified conventional insulin therapy. Although these therapies lead to better results than conventional insulin administration, there is no doubt that the problems of diabetes therapy can be solved only by an implantable AP or pancreas transplantation. PMID- 4015448 TI - The present and future of cardiac assist devices. AB - This article describes the status of development of an implantable electrically powered ventricular assist device designed for a minimum of a 2-year operation in patients with advanced heart failure. While these devices are envisioned for chronic support of the failing circulation, air-driven blood pumps have been used to provide life support to patients with acute ventricular dysfunction produced by a reversible myocardial injury of unknown origin. The physical and hemodynamic characteristics of the mechanical circulatory support devices are detailed. Clinical indications and results are provided on patients treated with temporary ventricular assist devices. Long-term follow-up of some patients has demonstrated sustained improved cardiac function for up to 5 years after treatment. Reperfusion injury and postischemic myocardial depression are discussed as two possible etiologies of acute ventricular dysfunction. In the summer of 1984, investigators began a collaborative program to test the engineering reliability of implantable devices as well as their performance in animals. This 3-year Device Readiness Program had a goal of demonstrating an 80% reliability with a confidence interval of 70%. In the future, the implantable device will be evaluated clinically in selected patients to investigate its ability to support circulatory functions and the results of host-device interactions. These devices have potential both as experimental tools in studies of heart and vascular disease and in the treatment of patients with intractable heart failure. PMID- 4015449 TI - Cardiac pacing in Japan. AB - A general update on pacemakers and cardiac pacing in Japan in 1981 is presented, including costs, prepacing studies, follow-up, pacing center activity, average number of first implants per million inhabitants, age of patients at first implantation, clinical indications for pacing, etiology, prepacing electrocardiogram, pacemaker hardware, electrode leads, electrocardiogram indications for pacing, indications for generator or electrode changes, and extended application of pacing. The author's data are compared with those obtained by the survey of the Seventh World Symposium on Cardiac Pacing. PMID- 4015450 TI - Clinical validation of a predictive modeling equation for sodium. AB - Changes in plasma sodium (Na) concentration during hemodialysis were predicted by changes in Na concentration of the dialysate at equilibrium with the plasma, according to the formula C't = CD - (CD - C'0) [(V0 - QFt)/V0]A/QF, where C'0 and C't are the Na concentration of the dialysate at equilibrium with the plasma at times 0 and t, respectively; QF is the ultrafiltration flow rate; V0 is the initial total body water; and CD is the Na dialysate concentration. This modeling involves only one parameter, A, which is the effective sodium dialysance and depends on the dialyzer, the QF, the plasma water flow rate, and the actual Donnan coefficient. Parameter A was evaluated after 1 h of dialysis. Seven routine 4-h dialysis sessions were performed in which the Na concentration of dialysate at equilibrium with the plasma was measured at varying times. The mean (+/- SEM) difference between predicted and measured values was delta C = 0.5 +/- 0.2 mmol/L. These data support the validity of the model that allows the monitoring of Na dialysate concentration to obtain a prescribed Na plasma concentration at the end of a dialysis session. PMID- 4015451 TI - What is the actual incidence of peritonitis in maintenance peritoneal dialysis? A prospective study. AB - Generally, the incidence of peritonitis in maintenance peritoneal dialysis programs is calculated as a percentage of the total number of treatments or as the number of episodes per patient-months. Both statistical methods give the wrong impression that peritonitis is seldom observed. However, peritonitis is still the major and unsolved challenge to successful long-term peritoneal dialysis. The lack of a standard and homogeneous definition of peritonitis is another critical point that prevents a rational interpretation of the published experiences. In the present study, dialysate cell counts of greater than 1,100 cells/mm3 were assumed to be the first sign of peritoneal infection. As long as more signs and symptoms are required for recognizing peritonitis (fever, abdominal pains, positive cultures), the statistical probability of making such a diagnosis shows the characteristics of a Poisson distribution. It is concluded that in long-term peritoneal dialysis, the currently used statistical methodology for evaluation of the incidence of peritonitis, including the clinical definition of this complication, is misleading. Dialysate cell counts appear to be the more sensitive sign for early diagnosis of peritonitis. PMID- 4015452 TI - Technical and clinical data on high-performance hemofiltration: twelve patients during one year. AB - In 12 chronic hemodialysis patients, postdilutional hemofiltration (HF) was substituted for conventional acetate hemodialysis (HD) (4-5 h/session with high area capillary dialyzers). In HF, the purposes were to obtain (a) no increase in pre-HF uremia compared with pre-HD uremia (high ultrafiltrate volume), (b) an HF duration shorter than that of HD (mean ultrafiltrate rate greater than 120 ml/min), (c) a disposable cost of an HF session identical to that of an HD session (reuse of hemofilters and extemporaneous preparation of substitution fluid). One-year results were (a) an ultrafiltrate volume of 26.8 L/session and a pre-HF uremia of 35.4 mmol/L (pre-HD uremia 34.0 mmol/L), (b) a mean ultrafiltrate rate of 143 ml/min and a mean HF duration of 190 min (mean HD session duration 250 min), and (c) better clinical tolerance and vascular stability in HF than in HD (weight loss 3.5 kg in HF and 3.0 kg in HD). Reuse of filters and extemporaneous preparation of substitution fluid were not responsible for any pyrogen reaction or bacterial contamination. In conclusion, (a) compared with conventional HD, high-flux HF results included identical removal of small molecules, improvement in vascular stability, decrease in session duration, and identical disposable cost; (b) routine high-flux HF is workable in a dialysis unit; (c) vascular access is the most important limiting factor to high-flux HF. Today 30-40% of patients can be treated with this method. PMID- 4015453 TI - Resin hemoperfusion in hepatic porphyrias. AB - In three types of hepatic porphyrias, 32 hemoperfusions over polyhema-coated Amberlite XAD-2 resin were performed. An attack of acute intermittent porphyria subsided after a 6-h hemoperfusion. During the procedure, 13 L of plasma was completely cleared of porphyrins. In a child with variegate porphyria, the laboratory changes were slight and no clinical effect of hemoperfusion was seen. In a patient suffering from porphyria cutanea tarda resistant to standard therapy, 30 hemoperfusions were performed during a period of 10 months. The total plasma porphyrin concentration increased sharply following the start of the treatment, and preceding the fifth procedure it reached a peak of four times the initial value. Since then, the plasma porphyrin level decreased, eventually to one-half the starting value. The mean drop in porphyrin level during each perfusion was 22%. Similar changes were observed in the amount of porphyrins excreted into the urine, which, following an early rise, decreased to 25% of the initial value. However, the patient's skin vulnerability improved only slightly. There were no untoward effects of the treatment. PMID- 4015454 TI - In vivo comparison of different algorithms for the artificial beta-cell. AB - Using an extracorporeal artificial beta-cell in chronically diabetic dogs, the effects of four different mathematical models of glucose-controlled insulin dosage were compared: the Biostator algorithm (quadratic equation), Toronto algorithm (hyperbolic tangent function), Karlsburg algorithm (modified first order derivative controller), and Ilmenau algorithm (second-order linear difference equation). The constants of all formulas implemented for the artificial beta-cell were obtained by regression analysis of paired blood glucose and plasma insulin data from normal control animals. Thus, they were biologically equivalent for all formulas. The patterns of blood glucose, insulin doses, and plasma insulin before, during, and after an intravenous glucose infusion test performed during the glucose-controlled insulin infusion showed no significant differences between the experimental groups subjected to the different algorithms. However, in no case were really normal blood glucose response curves restored by the artificial beta-cell. This might be due, first, to the fact that the algorithm parameters were not adapted to the actual individual insulin responsiveness, second, to the unphysiological peripheral venous route of insulin administration, and, third, to the lack of appropriate adaptation of the animals to normoglycemia. PMID- 4015455 TI - Mass transfer characterization of a new polysulfone membrane. AB - A new polysulfone capillary membrane has been tested ex vivo for its clearance performance under diffusive, combined diffusive and convective, and pure convective solute mass transfer. As was expected, increasing convective mass transfer produced augmentation only of clearances of high molecular weight solutes, and to a much lesser extent than reported for other membranes. This behavior is explainable by the enormous diffusive clearance capacity of the new membrane, which nearly reaches its theoretical maximal value, as derived from a computer model. Based on the very high hydraulic permeability, which makes this membrane equally suitable for filtrative and diffusive procedures, no membrane solute retention was found up to a molecular weight of 5,000 daltons. Stable hemocompatibility parameters (leukocytes, thrombocyte, and complement measurements) demonstrated absence of activation by this membrane during treatment. It is concluded that since its clearance performance is near the theoretical maximal and it shows superior biocompatibility, the membrane exhibits negligible interaction with the transported solutes independent of the transport mode. PMID- 4015456 TI - Relationship between mechanical and hydrodynamic properties of bioprosthesis produced from canine aortic valve. AB - Static tensile, stress relaxation, and hydrodynamic tests were carried out to investigate the relationships between the mechanical deformation or stiffness of heart valve leaflets and the opening behavior of bioprosthetic valves. The specimens used were fresh and glutaraldehyde (GA)-treated canine aortic valves. The tensile strength depended on the fiber orientation in the leaflet. The deformability of fresh and 0.05% GA-treated tissues was significantly larger than that induced by 0.1-5.0% GA concentrations according to the stress-strain curves. The stress relaxation function, which expresses the viscoelastic property, did not show significant differences in the 0.05-5.0% range of GA concentrations. In the hydrodynamic tests, the opening resistance of fresh and 0.05% GA-treated valves was less than that of 0.1-5.0% GA-treated valves. Thus, it was shown that the hydrodynamic valve functions were closely related to the material properties of aortic valve leaflets. PMID- 4015457 TI - Hydraulic driving unit and control system for artificial hearts. AB - A driving unit for artificial ventricles was constructed in which the power transmission is hydraulic. This avoids the danger of an air embolism, which is characteristic of pneumatic drives in the case of membrane rupture. An electromagnet as a power source drives a rolling membrane pump to move the transmission fluid to the artificial ventricle. This incompressible connection allows direct control of membrane motion and pumped blood volume simply by measuring the armature stroke. The volume-controlled mode is characterized by automatic self-regulation according to Starling's law and self-synchronization when the drive is used as a left (or right) ventricular assist device. Several measures were taken to increase the operational safety. The hemodynamic efficiency of the drive was tested in a number of in vivo experiments. The long term stability was proven in a 12-month durability test. PMID- 4015458 TI - New hollow-fiber dialyzers. PMID- 4015459 TI - New products for blood treatment. PMID- 4015460 TI - New hollow-fiber dialyzers. PMID- 4015461 TI - A prevalence survey of Parkinson's disease and other movement disorders in the People's Republic of China. AB - A door-to-door survey was conducted in six cities of the People's Republic of China. A total of 63,195 individuals were sampled during 1983 to determine the prevalence of major neurologic disorders. The survey involved a complete census, followed by a pretested interview and brief screening examination with a high level of sensitivity for detecting individuals with frequently occurring neurologic diseases, including movement disorders. Subjects with abnormal responses or findings were examined by a neurologist. There was 100% cooperation among the study subjects. Twenty-eight individuals alive on prevalence day (Jan 1, 1983) were identified as having Parkinson's disease, yielding an age-adjusted (to the 1960 US population) prevalence ratio of 57 per 100,000 population. All subjects were older than the age of 50 years. After the fifth decade of life, the age-specific prevalence ratios increased with age. PMID- 4015462 TI - Prognostic significance of hyperglycemia in acute stroke. AB - Prognostic significance of hyperglycemia on short-term survival was evaluated in 72 patients with acute hemispheric stroke. All patients were admitted within 48 hours of onset, and the neurologic deficit was assessed by means of a standardized score. A computed tomogram was taken in all cases on admission. Mortality was higher in hyperglycemic patients with no history of diabetes mellitus (78%) than in diabetic (45%) and in normoglycemic nondiabetic (29%) patients. In nondiabetic patients, the glucose level correlated with the neurologic score and with lesion size on computed tomogram. Reactive hyperglycemia due to a major stress response accounts for the worse prognosis of these patients. This correlation was not found in diabetic patients. Preexisting hyperglycemia, as well as systemic complications, could explain the higher mortality in these patients compared with normoglycemic nondiabetic patients. PMID- 4015463 TI - Spatial vision in Alzheimer's disease. General findings and a case report. AB - Visual contrast sensitivity to sinusoidal gratings of five spatial frequencies was measured in 15 patients with Alzheimer's disease and in eight control subjects. Contrast sensitivity thresholds were elevated at all frequencies in 14 patients compared with control subjects. The 15th patient was unique: she had an impairment in object and face recognition so severe that she could not recognize her husband visually. Her sensitivity to low and intermediate frequencies was markedly reduced in relation to that of other patients, whereas her sensitivity to the highest frequency tested equaled theirs. These observations emphasize the importance of low spatial frequency information for visual object and face recognition. PMID- 4015464 TI - Neurologic complications of gastric partitioning. AB - Six patients who had gastric reduction for morbid obesity suffered severe complex neurologic disturbances that included confusion and inappropriate behavior. All were profoundly weak or paraplegic, and recovery was delayed and incomplete. Encephalopathy was documented by EEG and neurologic examination. The cause is uncertain. Acute catabolism of lipid may predispose to damage of the nervous system, but relative vitamin deficiency is a more obvious and treatable explanation. PMID- 4015465 TI - Combined resting-postural tremors. AB - We studied eight patients with combined resting-postural tremors, which are classified as a subtype of essential tremor. Trihexyphenidyl hydrochloride, levodopa, and propranolol hydrochloride therapy were not effective in reducing these tremors. PMID- 4015466 TI - Radial compression neuropathy in advanced Parkinson's disease. AB - Radial compression neuropathy developed in four patients with advanced Parkinson's disease. Electrodiagnostic studies in two patients documented the upper middle part of the arm as the site of nerve injury. The conditions of three patients improved over four months. One markedly disabled, bradykinetic patient had a permanent flexion deformity of the wrist and hand. Radial compression neuropathy may be an initiating factor in the development of hand deformities in patients with late-stage parkinsonism. PMID- 4015467 TI - Muteness of cerebellar origin. AB - Acute bilateral damage to large areas of both cerebellar hemispheres including the dentate nuclei led to temporary loss of speech in six children. In each case muteness was unassociated with motor paralysis, loss of higher cognitive functions, or cranial nerve dysfunction. Muteness lasted one to three months. All patients were severely dysarthric during recovery. We conclude that transient muteness may result from acute bilateral cerebellar injury. PMID- 4015468 TI - Once-daily administration of phenobarbital in adults. Clinical efficacy and benefit. AB - The clinical anticonvulsant efficacy of once-daily administration of phenobarbital sodium was evaluated in 29 adults with head injuries. All patients were initially well controlled, with therapeutic blood levels of phenobarbital obtained from divided dose regimens, ranging from two to four daily administrations. All therapies were then converted to once-daily administration of the total dose at bedtime. Twenty-six patients (93%) remained within normal therapeutic blood levels without any dose change. Phenobarbital can safely, and perhaps should, be administered in a once-a-day regimen, with resultant benefits of probable increased compliance and decreased daytime sedation, if administered at bedtime. PMID- 4015469 TI - Optic neuritis and multiple sclerosis. PMID- 4015470 TI - Optic neuritis or multiple sclerosis. PMID- 4015471 TI - Optic neuritis and multiple sclerosis. PMID- 4015472 TI - Pituitary apoplexy. A review. AB - Pituitary apoplexy, a rare but life-threatening condition, may be highly variable in its clinical appearance and therefore should be considered in any patient with abrupt neurologic deterioration. We reviewed the literature on acute massive pituitary infarction to create an awareness of predisposing factors, the pathophysiologic mechanisms responsible for its heterogeneous manifestations, and possible options for investigation and management. These concepts are reinforced by examining the course and outcome of a rare case of pituitary apoplexy manifesting a full range of neurologic and endocrine abnormalities. PMID- 4015474 TI - Outpatient surgery. PMID- 4015473 TI - Severe compression neuropathy following sudden onset of parkinsonian immobility. AB - Prolonged immobility with adoption of unusual fixed body postures may lead to compression neuropathy. Although parkinsonism has not been considered to predispose to nerve compression, we report three patients with Parkinson's disease and on-off motor fluctuations who developed severe compression neuropathy following a sudden onset off period. The stereotyped posture assumed by parkinsonian patients during an off period appears to make them especially prone to injury of the radial nerve in the upper arm and the brachial plexus. PMID- 4015475 TI - Childhood esotropia. PMID- 4015476 TI - Prospective evaluation of radial keratotomy (PERK) study patients. PMID- 4015477 TI - Unsuccessful laser cyclophotocoagulation for glaucoma in aniridia. PMID- 4015478 TI - Vibrio conjunctivitis. PMID- 4015479 TI - Symptoms of allergic conjunctivitis. PMID- 4015480 TI - Prevention of fluorescein dye extravasation. PMID- 4015481 TI - How should we manage a patient with uveal melanoma? PMID- 4015482 TI - Comparison of prognosis after enucleation vs cobalt 60 irradiation of melanomas. AB - Between December 1962 and May 1979, growth of choroidal and ciliary body melanomas was documented in 34 patients prior to enucleation. Twenty-seven of the 34 patients underwent enucleation during the same time period (1967 through 1976), when primary treatment with a cobalt 60 episcleral plaque was employed in a nonrandomized fashion in 21 patients with similar-sized melanomas. Comparison of these two groups of patients, none of whom was unavailable for follow-up and all of whom were followed up for a minimum of 66 months, showed that the probability of dying of metastatic melanoma within five years after cobalt 60 therapy was 50% compared with 16% after enucleation. Factors of potential importance in explaining this difference included nonrandomization, small number of patients in both groups, and greater frequency of anterior location of tumors in the cobalt 60 group (76% vs 22%). A randomized, controlled clinical trial is required to determine the relative safety of treatment for uveal melanomas. PMID- 4015483 TI - Comparison of uveal melanoma growth rates with mitotic index and mortality. AB - Between December 1962 and May 1979, growth of choroidal and ciliary body melanomas was documented in 34 patients prior to enucleation, and in one patient whose eye was obtained at autopsy. Melanoma growth rates in 33 of these 35 eyes were calculated and compared with mitotic index, tumor cytology, tumor size, and mortality. Each melanoma appeared to grow at a constant rate that varied widely in different melanomas. Growth rate correlated with mitotic index. Most large tumors and epithelioid and mixed cell melanomas demonstrated fast growth rates. Most melanomas causing death contained epithelioid cells and were growing rapidly. These findings do not support the conclusion of Zimmerman and colleagues that enucleation is responsible for most metastatic deaths. Rather, it argues against one of the fundamental assumptions on which their conclusion is based, namely, that all melanomas have a relatively uniform slow growth rate prior to enucleation. PMID- 4015484 TI - Intraocular metastases from cutaneous malignant melanoma. AB - We present a consecutive series of ten patients (12 eyes) with symptomatic intraocular metastases from primary cutaneous malignant melanoma, with emphasis on the variation in clinical features and extent of intraocular involvement. An investigation of each patient's history and the presence of other concurrent metastatic foci help to establish the diagnosis. Palliative radiation therapy may help to control the intraocular metastatic foci and limit the visual loss. PMID- 4015485 TI - Retinoblastoma and retinoma occurring in a child with a translocation and deletion of the long arm of chromosome 13. AB - A young girl who had an active retinoblastoma in the left eye, and a retinoma or spontaneously regressed retinoblastoma in the right eye, was found to have a complex translocation-deletion involving chromosomes 13 and 10. Karyotypic analysis suggested that three simultaneous breaks had led to the interchange of centric and telomeric regions of chromosome 10 and 13, with loss of an interstitial acentric fragment from 13, which included subband 13q14.2. The child is intellectually retarded, and has the characteristic midface appearance associated with 13q-deletion syndrome. It is believed that this is the first report of a case of retinoblastoma and retinoma occurring in association with 13q deletion syndrome. PMID- 4015486 TI - Massively invasive diffuse choroidal melanoma. AB - A 74-year-old woman was found to have increasing proptosis in a blind, painful left eye with neovascular glaucoma. Uveal malignant melanoma with massive orbital involvement was diagnosed, and the patient underwent orbital exenteration, with preoperative and postoperative orbital irradiation. The tumor was a mixed-cell, diffuse uveal malignant melanoma with involvement of the optic nerve adjacent to the line of surgical transection and of the optic nerve sheath. Subsequently, the cerebrospinal fluid cytology disclosed cells consistent with malignant melanoma, despite the absence of neurologic signs or symptoms. Cerebrospinal fluid cytology is essential in such cases, and ultrasonography is of value. PMID- 4015487 TI - Topical fluorouracil. Pharmacokinetics in normal rabbit eyes. AB - Postoperative subconjunctival fluorouracil injections may be a useful adjunct to standard glaucoma filtering surgery in eyes that are at high risk of failure. Topical administration would be preferable to subconjunctival administration; however, there are no data on the ocular penetration of topically applied fluorouracil. Consequently, we investigated the pharmacokinetics of topically administered fluorouracil labeled with carbon 14 in normal rabbit eyes. One drop (approximately 2.4 mg) of fluorouracil resulted in the following concentrations at 0.5 and six hours, respectively: 17.3 and 0.9 micrograms/g of conjunctiva; 24.3 and 1.3 micrograms/g of cornea; 14.6 and 0.2 micrograms/mL of aqueous; 0.8 and 0.5 microgram/g of lens; 1.1 and 0.3 microgram/g of vitreous; and 0.2 and less than 0.1 microgram/mL of serum. Three drops (approximately 7.2 mg) of fluorouracil resulted in the following concentrations at 0.5 and eight hours, respectively: 589.8 and 1.3 micrograms/g of conjunctiva; 502.9 and 1.8 micrograms/g of cornea; 199.6 and 0.8 micrograms/mL of aqueous; 6.2 and 0.5 micrograms/g of lens; 6.8 and 0.5 micrograms/g of vitreous; and 1.3 and 0.2 microgram/mL of serum. Since a fluorouracil concentration of 0.2 microgram/mL inhibits rabbit conjunctival fibroblast proliferation in cell culture by 50%, these data suggest that topically applied fluorouracil achieves sufficient levels in the ocular compartments and tissues to have potential therapeutic applications. PMID- 4015488 TI - Optic nerve head blood flow in chronic experimental glaucoma. AB - We used the tritiated iodoantipyrine method to estimate blood flow in the retina, optic nerve head, and retrobulbar optic nerve in monkey eyes. Twelve eyes with short-term intraocular pressure (IOP) elevation and nine eyes with long-term (up to 20 months) IOP elevation were compared with their fellow normal eyes. The eyes with long-term glaucoma were staged for degree of optic nerve damage according to disc cup size, nerve fiber layer atrophy, and histologic estimates of the remaining number of nerve fibers. At normal IOP levels, there were only minor differences in blood flow in the superior, inferior, and middle nerve head sections. In eyes with short-term IOP elevation, nerve head blood flow was normal, unless IOP exceeded 75 mm Hg. Above this level, a progressive decrease in nerve head blood flow was measured. Mean blood flow in the nerve head of eyes with long-term glaucoma was not significantly different from that in the normal fellow eyes. Some animals had small increases in blood flow, while others had small decreases. These differences from normal did not correlate with the amount or location of optic nerve damage. Our data do not support decreased blood flow as part of the pathogenesis of long-term experimental glaucoma. PMID- 4015489 TI - Slit-lamp fluid-gas exchange and other office procedures following vitreoretinal surgery. AB - Many complicated postoperative vitreoretinal cases require reoperations. It is possible to perform some of these procedures outside the operating room. We describe examining room techniques for fluid-gas exchange, fluid and gas aspiration, and adherent vitreous strand removal. We also discuss a slit-lamp technique for using sodium hyaluronate (Healon) following fluid-gas exchange to eliminate optical distortion from endothelial striae. PMID- 4015490 TI - New Zealand. Ophthalmology, medical education, and national background. PMID- 4015491 TI - Trapdoor effect in nasolabial flaps. Causes and corrections. AB - The trapdoor effect is an elevated and bulging deformity of tissue within the semicircular confines of a U-, C-, or V-shaped scar. Various theories to explain this phenomenon are lymphatic and venous obstruction, hypertrophy of the scar, excessive fatty and redundant tissue, beveled wound edges, and contracture of the scar. Our data suggest that scar contracture is the predominant cause of the trapdoor effect in nasolabial flaps. For mild to moderately severe trapdoor deformities, multiple, small Z-plasties about the periphery of the nasolabial flap are indicated. Intralesional triamcinolone acetonide injections may produce a "pharmacologic Z-plasty" effect in some trapdoor deformities. For marked trapdoor deformities, the combination of multiple, small Z-plasties along the semicircular scar and peripheral undermining about the trapdoor defect is the corrective procedure. The trapdoor deformity may be prevented or lessened by peripheral undermining about the recipient site of the flap equal to or greater in area than the recipient site. PMID- 4015492 TI - Oblique forehead flap for total reconstruction of the nasal tip and columella. AB - The oblique forehead flap provides sufficient tissue for total reconstruction on the nasal tip and columella. In the majority of cases, the secondary defect of the forehead can be closed primarily. Thus, the oblique forehead flap often obviates the need for a scalping flap, which is a surgical procedure of greater magnitude and results in more significant secondary deformity of the skin of the forehead. PMID- 4015493 TI - The 'note flap'. AB - A versatile local skin flap for the closure of facial defects is presented. A tangent is drawn to the edge of a circular defect parallel to the relaxed skin tension lines for a distance of 1.5 diameter (d); a second line of length d is drawn at 50 degrees to 60 degrees to the first to create a triangular flap. The final flap design when drawn resembles an eighth note. The tip of the flap is de epithelialized to facilitate closure. Two opposing flaps can be used for a larger defect if desired. In a series of 20 consecutive patients, the mean length of the first side of the flap was 1.4d, the length of the second was 1.1d, and the mean tip angle was 50.3 degrees. The area of this average flap is approximately 75% of the area of the circular defect. Skin deformation measured on piglets showed the major tension vector to be perpendicular to the tangential side of the triangular flap. PMID- 4015494 TI - Advances in laser skin surgery for vascular lesions. AB - Recent advances in laser techniques for the treatment of vascular lesions have attempted to overcome the disadvantages of argon laser therapy. The trend toward a more selective treatment of these lesions, with preservation of as much normal tissue as possible, has been set. Minimal argon laser methods, yellow-dye lasers, and treatment with hematoporphyrin derivative photodynamic therapy extend the abilities of the laser surgeon to treat port-wine stains and other vascular lesions safely. PMID- 4015495 TI - Use of electrosurgery in blepharoplasty. AB - The use of electrosurgery in blepharoplasty is controversial. The reluctance to use this technique may be related to a misunderstanding of the principles of electrosurgery and to uncertainty about its physical effects on local tissues. On the basis of a review of the physics of electrosurgery, our personal technique, and our clinical results, we feel the method is safe and may offer several advantages over traditional techniques. PMID- 4015496 TI - Support of unstable nasal fractures with silicone rubber wedge splints. AB - Successful treatment of unstable fractures of the nasal dorsum is often precluded due to inadequate stable postoperative support of the fragmented dorsum. As an adjunctive measure in the treatment of nasal fractures, intranasal silicone rubber (Silastic) wedges transfixed to internal and/or external plates can provide support of unstable dorsal fragments. In a series of 20 cases, there was no incidence of remaining postoperative dorsal depression and no evidence of foreign-body reaction. PMID- 4015497 TI - Laser turbinectomy as an adjunct to rhinoseptoplasty. AB - One hundred two inferior turbinectomies were done with the carbon dioxide laser as an adjunct to rhinoseptoplasty. Indications for surgery were airway obstruction on one or both sides not relieved by medical means (42 cases), patient inability to tolerate medication (36 cases), and patient unwillingness to continue to receive medication for prolonged periods (24 cases) in patients unhappy with their appearance. Pathologic processes included allergic rhinitis (34 cases), vasomotor rhinitis (28 cases), and rhinitis medicamentosum (40 cases). A newly designed suction speculum provided easy access to the internal nose and protected the alar rim and the face from laser energy. Only a few minutes of extra operating time were required. Relief of obstruction was comparable to that obtained from cryosurgery, submucous resection of the turbinate, and partial turbinectomy. Intraoperative and postoperative bleeding was less with laser turbinectomy than with any other means. PMID- 4015498 TI - An approach to large nasoseptal perforations and attendant deformity. AB - Six patients with symptomatic large anterior septal perforations were treated for relief of symptoms and the frequently concomitant saddle-nose deformity. The patients required large anteriorly and posteriorly based rotation flaps consisting of mucoperiosteum from the floor, lateral wall, and inferior turbinate of the nose. PMID- 4015499 TI - External rhinoplasty approach to transsphenoidal hypophysectomy. AB - The history of transsphenoidal hypophysectomy demonstrates the soundness of the basic concept of approaching the sella turcica in a midline fashion through the nose. Conceptually, it has not been eclipsed since first evolved by Cushing in the early part of this century. The surgical advances since Cushing's time have been major refinements in instrumentation and minor refinements of his basic technique. The external rhinoplasty approach is such a refinement. We have used this technique in a two-year period between June 1982 and June 1984 on 14 patients. We have found this technique for transsphenoidal hypophysectomy to be a simple, reliable, rapid technique for exposing the septum and the floor of the nose. It provides excellent exposure to the sphenoid sinus and pituitary gland without loss of nasal tip projection or other cosmetic deformity. PMID- 4015500 TI - Mandibular reconstruction with the A-O plate. AB - At the University of Minnesota and affiliated hospitals several methods of mandibular reconstruction have been used. From October 1978 through March 1984, 11 patients have undergone reconstruction with the A-O plate technique. These patients had both traumatic and oncologic defects. All patients treated with this technique have achieved a solid mandibular arch. Included is a discussion of the theoretical advantages, preoperative prerequisites, and the operative technique. PMID- 4015501 TI - Glottic reconstruction with thyroid perichondrium and investing cervical fascia. AB - Various surgical procedures have been designed for glottic reconstruction following vertical partial laryngectomy. Many of these techniques require flaps or even a second stage to adequately compensate for the loss of lining or bulk that accompanies extended laryngeal resection. Thyroid perichondrium and investing cervical fascia were used in 20 cases of glottic reconstruction. Laryngeal reconstruction following vertical partial laryngectomy using readily available local tissue allows for the wide resection of tumor as well as for the preservation of laryngeal structure and function. PMID- 4015502 TI - Salmonella dublin neck abscess. AB - Salmonella dublin infection is usually a veterinary disease. However, human outbreaks have occurred, mostly following consumption of contaminated raw milk. Salmonella dublin has a predilection for the immunocompromised host and usually causes a severe illness with fever, diarrhea, and bacteremia. PMID- 4015503 TI - Fibromatosis and fibrosarcoma of the larynx and pharynx in an infant. AB - A 14-month-old infant had congenital solitary fibromatosis of the larynx that showed fibrosarcomatous change and that spread to the pharynx and the anterior part of the neck. The histologic condition is discussed, as is the surgical treatment with total laryngopharyngectomy. A five-year postoperative follow-up is included. PMID- 4015504 TI - Laryngeal perichondritis and abscess. AB - Primary infection of the laryngeal cartilages has become rare in the antibiotic era. However, trauma, irradiation, a foreign body, or cancer may initiate the infection, particularly in the immunocompromised patient. We encountered three cases of perichondritis and abscess associated with airway intubation, nasogastric intubation, and external beam radiotherapy. Laryngeal perichondritis and abscess remain serious potential causes of laryngeal deformity and dysfunction. PMID- 4015505 TI - A new concept of impaired glucose tolerance. Relation to cardiovascular risk. PMID- 4015506 TI - Regulation of high density lipoprotein binding activity of aortic endothelial cells by treatment with acetylated low density lipoprotein. AB - High density lipoprotein (HDL) binding to human fibroblasts and arterial smooth muscle cells is up-regulated when sterol is delivered to cells in the form of nonlipoprotein cholesterol or low density lipoprotein (LDL). Results from the present study show that the HDL binding activity of aortic endothelial cells is up-regulated when cholesterol in the form of acetylated LDL (AcLDL) is delivered to cells via the "scavenger" lipoprotein receptor pathway. AcLDL treatment led to a dose-dependent, but saturable, increase in HDL binding to cultured bovine aortic endothelial cells that was reversed when cells were treated with lipoprotein-deficient serum. The AcLDL-mediated enhancement in HDL binding activity was inhibited by cycloheximide, suggesting the involvement of protein synthesis. This enhancement was associated with an increased cell cholesterol content, a suppressed rate of cholesterol synthesis, and an increased rate of cholesterol ester formation. Kinetic analysis of HDL binding showed that AcLDL treatment caused an increase in the apparent number of high-affinity binding sites (Kd approximately 3 micrograms/ml HDL protein). Competition and direct binding studies revealed that the inducible binding sites exhibited relative specificity for HDL over LDL and AcLDL. Thus, aortic endothelial cells appear to possess specific receptors for HDL that may function to facilitate HDL-mediated removal from cells of excess cholesterol internalized by the scavenger receptor pathway. PMID- 4015507 TI - Structural and hemodynamic response of peripheral arteries of macaque monkeys to atherogenic diet. AB - The arteries of monkeys given atherogenic diets develop marked intimal thickening and medial thinning, but luminal size apparently changes minimally. The hemodynamic significance of the atherosclerotic changes is therefore uncertain. To evaluate vascular function in atherosclerotic arteries, we studied the hind limb vessels of adult male rhesus and cynomolgus monkeys to assess the structural and hemodynamic responses to an atherogenic diet given for about 1.5 years or for much longer periods (6.5 years for rhesus and 4.3 years for cynomolgus monkeys). The intimal cross-sectional area greatly increased after the atherogenic diet, but there was no significant luminal narrowing after either the 1.5-year diet or the longer diet periods. The media of atherosclerotic arteries showed focal atrophy and focal thinning after pressure fixation, but the total medial mass was not decreased even after the long diet periods. Hemodynamic studies indicated mild functional impairment in the atherosclerotic vessels; resting resistance increased and vasodilator responses decreased, but adrenergic responses were preserved. Thus, the marked changes that occur in the arterial wall in experimental primate atherosclerosis include adaptations to lesion formation that permit a long prestenotic phase of atherosclerosis in which vascular dysfunction is minimal. PMID- 4015508 TI - Cholesterol metabolism in juvenile baboons. Influence of infant and juvenile diets. AB - The deferred effects of infant diets and the effects of juvenile diets on cholesterol metabolism were estimated in 83 baboons (Papio sp.) at 3.5 years of age. As infants, the animals were breast-fed or fed one of three formulas containing approximately 2, 30, or 60 mg/dl cholesterol. After weaning at 14 weeks of age, the animals were fed one of four juvenile diets high or low in cholesterol with saturated (P/S = 0.37) or unsaturated (P/S = 2.1) fats. Cholesterol absorption and cholesterol turnover were measured by fecal isotopic methods, and variables of cholesterol metabolism were estimated from a two-pool model. Among juvenile animals breast-fed during infancy, the percentage of cholesterol absorption was higher, while the fluxes of cholesterol from Pool A (QAA, QA, and QAB) and the cholesterol mass of Pool B were lower, compared to those fed formulas. The level of cholesterol in formulas fed during infancy did not influence cholesterol metabolism during the juvenile period. During the juvenile period, saturated fat significantly decreased the cholesterol production rate (QA) and increased the rate constants for cholesterol flux between Pool A and Pool B (KAB and KBA) compared to unsaturated fat. High cholesterol intake increased bile acid and neutral steroid excretion, cholesterol turnover rate, the mass of Pool A, and the rate constant KA and fluxes QA and QAA for removal of cholesterol from Pool A. However, KAB, t1/2 B (half-time of Pool B), and the percentage of cholesterol absorbed were decreased.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4015509 TI - Effect of acetylsalicylic acid on pulmonary arteriosclerosis induced by a one year Dirofilaria immitis infection. AB - The ability of aspirin to block arteriosclerosis that developed in response to chronic, low-level injury to pulmonary arteries was evaluated in 21 dogs during their 1-year infection with Dirofilaria immitis. Three groups, with seven dogs in each group, were studied before and after sustained injury produced by the transplantation of 28 adult Dirofilaria immitis into each dog. Group A received no treatment and served as controls; Group B received no treatment for 6 months and then received 7 mg/kg of aspirin daily) for 6 months; Group C received 7 mg/kg of aspirin daily for the entire year. The pulmonary arterial response was evaluated by hemodynamic and arteriographic studies at 6 and 12 months and by scanning electron microscopy at the end of the 12-month study. All groups developed a similar, mild pulmonary hypertension. The arteriographic changes of dilation and flow obstruction were worse in Groups A and B than in Group C at 6 months, and at 12 months both Groups B and C were less obstructed than Group A. Scanning electron microscopy revealed large, complex myointimal proliferations in Group A, whereas the two aspirin-treated groups had smaller, less complex lesions that covered a much smaller surface area. We concluded that: 1) aspirin markedly reduced the microscopic and macroscopic arteriosclerosis in Groups B and C; 2) aspirin in Group B not only arrested further development but also permitted resolution of arteriosclerosis while the arteries were still being injured. PMID- 4015510 TI - Relative contribution of triglyceride-rich lipoprotein particle size and number to plasma triglyceride concentration. AB - These studies were undertaken to determine whether differences in plasma triglyceride concentrations reflected differences in the number or in the size of the triglyceride-rich lipoprotein particles in the circulation. A population of 122 men and women, composed of normotriglyceridemic individuals and individuals with endogenous hypertriglyceridemia (plasma triglyceride concentration from 60 mg/dl to 1400 mg/dl), was studied by one of four independent experimental procedures. Rates of triglyceride production and particle (as reflected by apolipoprotein B) production were simultaneously determined. The data suggest that 71% of any increase in triglyceride production was due to an increase in the production of particles, and only 29% was due to an increase in the amount of triglyceride carried per particle. Direct measurement of the triglyceride-rich lipoprotein particle size by electron microscopy demonstrated that for a fivefold difference in triglyceride borne by the Sf 12-400 lipoproteins (from 100 mg to 500 mg triglyceride/dl plasma), the mean particle size rose by only 29%. Hence, 71% of this difference was due to an increase in particle number. The same results were obtained when triglyceride levels were related to the number of triglyceride-rich lipoproteins in the plasma. The number of particles for these studies was either estimated from apo B concentration or by calculations based on the chemical composition of ultracentrifugal subfractions. These studies have used four different approaches to show that changes of plasma triglyceride concentration primarily reflected a change in the number, not the size, of triglyceride-rich lipoprotein particles. Our studies also demonstrated that 75% to 80% of the triglyceride-rich lipoproteins in both normotriglyceridemic and hypertriglyceridemic subjects were in the Sf 12-60 or intermediate density lipoprotein subfraction. PMID- 4015511 TI - Plasma lipoprotein levels in treated and untreated hypertensive men and women. The National Heart Foundation of Australia Risk Factor Prevalence Study. AB - Experimental studies have reported that common antihypertensive drugs such as diuretics, beta-blockers, and methyldopa have adverse effects on plasma lipids and lipoproteins. To investigate whether such effects can be observed in the general population, plasma lipid and lipoprotein levels were compared in subjects receiving antihypertensive treatment, subjects with untreated high blood pressure, and subjects with normal blood pressure in a random sample of 5603 subjects screened in a national study of risk factor prevalence in Australia. In both sexes, high density lipoprotein (HDL) cholesterol was lower in the group receiving treatment than in the others (p less than 0.001). In men, triglycerides (TG) (p less than 0.001) and the ratio of total cholesterol to HDL cholesterol (TC/HDL cholesterol) (p less than 0.05) were higher in the group receiving treatment. In both sexes, the differences in plasma lipids and lipoproteins between treated and untreated hypertensive groups were independent of age, body mass index, alcohol consumption, and smoking. More than 40% of the treated or untreated hypertensive men and women had elevated total cholesterol (TC greater than 252 mg/dl) or an elevated TC/HDL cholesterol ratio (greater than 6.0). In men receiving antihypertensive treatment, the prevalence of an elevated TC/HDL cholesterol ratio was significantly greater than in men with untreated high blood pressure (p less than 0.01). The results of this study suggest that the effects of antihypertensive treatment on plasma lipids and lipoproteins can be observed in population lipid and lipoprotein levels. Even before treatment, a large proportion of high blood pressure patients have a significant plasma cholesterol abnormality, which may be aggravated by conventional antihypertensive therapy. PMID- 4015512 TI - Measurement of 125I-LDL entry into ballooned rabbit aorta using average plasma value. PMID- 4015513 TI - Calmodulin in breast milk, and umbilical and maternal plasma. PMID- 4015514 TI - Surgical induction of labour. PMID- 4015515 TI - Diagnostic colposcopy in adenocarcinoma of the uterine cervix. PMID- 4015516 TI - The pattern and attitude of Nigerian women in Benin City towards female sterilisation. PMID- 4015517 TI - Dose-response relationship between dose of clomiphene citrate and incidence of ovulation. PMID- 4015518 TI - Characteristics of induced labour. PMID- 4015519 TI - The physiological role of the sitting parturient posture. PMID- 4015520 TI - The effect of electro-cutting and diathermy coagulation on wound healing in gynecological surgery. PMID- 4015521 TI - Neonatal hyperbilirubinemia in oxytocin augmented labour. PMID- 4015522 TI - Danazol (an antigonadotropin) in the treatment of catamenial pneumothorax. PMID- 4015523 TI - A certain kind of madness. Authentic case histories from Australian general practice. PMID- 4015524 TI - Change in hospital access for GPs prompts a research project. PMID- 4015526 TI - Mammography--more harm than good? PMID- 4015525 TI - Diagnosis and management of pancreatic cancer. PMID- 4015527 TI - Screening for breast cancer in apparently well women. PMID- 4015529 TI - Radiological examination of women. Modification of the 10 day rule. PMID- 4015528 TI - Colorectal cancer screening. Faecal occult blood tests. PMID- 4015531 TI - When breast is not best. PMID- 4015530 TI - Chronic leg ulcers. Ozone and other factors affecting healing. PMID- 4015532 TI - Practical treatment for insomnia. PMID- 4015533 TI - Sydney funnel web spider bite. PMID- 4015534 TI - Chest pain and the diagnosis of angina. PMID- 4015535 TI - Sigmoidoscopy. PMID- 4015536 TI - Abdominal pain beyond belief. PMID- 4015537 TI - Paronychia. PMID- 4015538 TI - The glandular fever virus. PMID- 4015539 TI - International travel and infection. PMID- 4015540 TI - Unusual arthropod ectoparasitic infestations of man. PMID- 4015541 TI - The family history. PMID- 4015542 TI - Respiratory tract infections. PMID- 4015543 TI - Suitable alternatives to Debendox for morning sickness in pregnancy. PMID- 4015544 TI - Tumour markers. A clinical review. PMID- 4015545 TI - Recent advances in paediatrics. PMID- 4015546 TI - Marital and family breakdown. Thoughts on the role of doctors, lawyers and behavioural scientists. PMID- 4015547 TI - Standards of accreditation. Teaching posts in general practice. PMID- 4015548 TI - Regulation of immunity and tolerance to type III pneumococcal polysaccharide (SIII) by functionally distinct IgM anti-SIII antibodies. AB - When BALB/c mice and athymic (nude) mice are injected intraperitoneally (i.p.) with pneumococcal type III polysaccharide (SIII), their antibodies as measured by passive haemagglutination (HA) are inhibited more easily by high doses of SIII than antibody measured by passive haemolysis (HL). The HA activity, due mainly to a highly avid non-complement-fixing (NCF) type of IgM, was further distinguished from the HL activity (CF-IgM, or CF-IgM plus CF hybrid IgM/A anti-SIII antibodies) by the failure of the NCF-IgM anti-SIII to bind to protein-A of Staphylococcus aureus (Sa). High-dose tolerance in the HL anti-SIII antibody response of BALB/c and athymic mice was induced only in the absence of circulating NCF-IgM anti-SIII antibodies. The presence of NCF-IgM anti-SIII antibodies formed to multiple daily increasing amounts of SIII, commencing with 0.01 micrograms SIII, decreased the magnitude of the HL anti-SIII response to subsequent daily increments of SIII antigen injected into BALB/c and athymic (nude) mice. Thus, the effect on the HL anti-SIII response was independent of T cells. The concomitant administration of NCF-IgM anti-SIII rendered SIII less tolerogenic in primed mice. In contrast to the HL activity, the NCF-IgM anti-SIII antibodies were induced to low doses of SIII, conferred protection against viable pneumococci, but did not precipitate the soluble antigen in agar. It is proposed that immune paralysis (as defined by the failure of SIII-injected mice to resist pneumococcal challenge) is not necessarily a condition of total unresponsiveness but is due to an absence of protective NCF-IgM anti-SIII antibodies. Thus, immune paralysis can co-exist with either the presence or absence of non-protective CF IgM or CF-IgM/A anti-SIII antibodies. PMID- 4015549 TI - Epithelial cell renewal and antibody transfer in the intestine of the foetal and neonatal lamb. AB - The intestine of the foetal lamb was exposed to large quantities of alpha globulin (IgG) by prolonged intra-duodenal infusion, and absorption of intact IgG, with transfer to the lymph, continued undiminished, i.e., there was no evidence of closure. The rate of proliferation of the intestinal epithelium of the foetal and newborn lamb was measured using mitotic indices and localised labelling with (3H)-thymidine (TdR). In the foetus, cell division in the crypts occurs at a lower rate than the newborn (p less than 0.001) and there is very slow replacement of the intestinal epithelium. In the newborn lamb, a portion of the small intestine was incubated in vivo with TdR and the progress of labelled cells from the crypts upwards along the villi estimated, using autoradiography of serial biopsies from the same animal. A front of mature, digestive epithelium could be seen advancing up the villi, displacing the immature foetal type of cell which was capable of transfer of intact IgG to the lymphatics of the intestine. The evidence presented supports the hypothesis that immediately after birth the intestinal epithelium of the lamb begins to be replaced by a digestive type of cell, and the layer of cells responsible for absorption of colostral antibodies progressively disappears from the villi, resulting in closure. PMID- 4015550 TI - In vitro development of zinc-deficient and replete rat embryos. AB - The development of the zinc-deficient rat embryo has been studied in vitro using embryo culture techniques. Normal 9.5 day embryos cultured for 48 h in serum obtained from zinc-deficient rats grew and developed to the same extent as those cultured in zinc-replete serum. Embryos from dams which had been fed a zinc deficient diet since mating were also removed for culture. Such zinc-deficient embryos fell into two broad morphological categories. One group appeared identical to the normal embryos, while the others had apparently normal visceral yolk sacs but small embryonic poles and retarded or abnormal embryonic development. Culture of the first group in either zinc-deficient or replete serum produced morphologically normal embryos; however, those which appeared abnormal at day 9.5 were grossly malformed after 48 h incubation in either sera. When embryos were cultured in the presence of 65Zinc, the most severely affected zinc deficient embryos accumulated as much zinc as the zinc-replete and apparently unaffected zinc-deficient embryos, indicating that the malformations do not arise from an inability of the embryo or yolk sac to accumulate zinc from the surrounding fluid. The results from these studies suggest that the teratogenic effects of zinc deficiency cannot be induced by direct culture of zinc-replete embryos in zinc-deficient serum. Furthermore, it would appear that maternal zinc deficiency can exert its teratological influence prior to day 9.5 of gestation and that these effects are not readily reversible. PMID- 4015551 TI - Aggravation of experimental atherosclerosis in vasectomized, cholesterol-fed rabbits. AB - Rabbits were fed a stock or atherogenic diet for a period of fourteen months. Half of each group of rabbits was bilaterally vasectomized while the other half underwent sham vasectomy. The level of plasma cholesterol was significantly elevated following vasectomy in stock diet-fed rabbits. Atherogenic diet feeding caused marked elevation of plasma cholesterol in both vasectomized as well as sham-vasectomized animals. At the termination of the experiments, aortic cholesterol in stock diet-fed vasectomized rabbits remained unchanged, but this was increased in both vasectomized and sham-vasectomized atherogenic diet-fed animals. Aortic sudanophilia, atherosclerotic plaque size and coronary atherosclerosis index were significantly increased in vasectomized atherogenic diet-fed rabbits as compared to their controls. In stock diet-fed vasectomized rabbits no macroscopic or microscopic lesions were seen even in the presence of mild hypercholesterolaemia. PMID- 4015552 TI - Candidiasis in a musk lorikeet (Glossopsitta concinna). PMID- 4015553 TI - Dose rate, time of injection and litter size effects on dexamethasone-induced parturition in Border Leicester x Merino ewes. PMID- 4015554 TI - Use of suxamethonium in cats fitted with dichlorvos flea collars. PMID- 4015555 TI - Suspected poisoning of horses by Trema aspera (poison peach). PMID- 4015556 TI - The supply of veterinary graduates. PMID- 4015557 TI - Specific antibody responses to Taenia hydatigena, Taenia pisiformis and Echinococcus granulosus infection in dogs. AB - Groups of dogs reared free of both nematodes and cestodes were infected with Taenia hydatigena, Taenia pisiformis or Echinococcus granulosus. After infections with the Taenia spp became patent, dogs were purged to remove the worms. They were later reinfected and the second infections again removed by purging after patency. A group of 3 uninfected worm free dogs was kept as age-matched controls. The dogs were bled at intervals of 5 days and their serums tested for antibodies using the enzyme-linked immunosorbent assay (ELISA) with excretory/secretory (ES) antigens collected during in vitro incubation of evaginated scoleces (scolex ES antigen) and oncosphere antigens. Antibodies to scolex ES antigen were detected by 3 weeks after infection with each cestode species whereas antibodies to oncosphere antigen were not detected until about one week after eggs were found in the faeces of the infected dogs. Antibody responses to both oncosphere and scolex ES antigens decreased rapidly following removal of the worms by purging. Uninfected control dogs were invariably negative to both oncospheral and scolex ES antigens. There were cross-reactions between the serums from dogs infected with T. pisiformis and T. hydatigena when tested with scolex ES antigens, but oncospheral antigens showed a high degree of species specificity. Scolex ES antigens from E. granulosus were compared with those prepared from T. hydatigena and T. pisiformis for their ability to discriminate between antibodies in serums collected from dogs 31 and 32 days after infection with 100,000 protoscoleces of E. granulosus or dogs infected with Taenia spp.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4015558 TI - Ocular inserts for application of drugs to bovine eyes--in vitro studies on gentamicin release from collagen inserts. AB - Soluble collagen and insoluble collagen films were impregnated with gentamicin and investigated in vitro as vehicles for the delivery drugs. Succinylated collagen released significantly higher levels of antibiotic than the insoluble films, and maintained mean inhibitory concentrations (MIC) for Moraxella bovis for 24 h. PMID- 4015559 TI - Failure of oral zinc therapy to alleviate Bacteroides nodosus infections in cattle and sheep. AB - Cattle and sheep with Bacteroides nodosus infection were treated orally with both high (65 mg Zn/kg and 82 mg Zn/kg) and low (1 mg Zn/kg and 8.6 mg Zn/kg) doses of zinc sulphate respectively. The lower dose rates administered weekly for one month, in the case of cattle, or daily for 2 weeks, in the case of sheep, had no effect either on serum zinc levels or the prevalence or severity of infection in treated animals. High dose rates of zinc (approximately 2.5 g Zn per head per day) were required to elevate serum levels above those normally present in both cattle and sheep. Even these dose rates continued daily for about 2 weeks had no beneficial effect on B. nodosus infection in either species. PMID- 4015560 TI - A retrospective study of head fractures in 21 horses. AB - The clinical features of 21 horses which sustained head fractures are reviewed. There was a higher incidence of fractures in males and Standardbred horses. Surgical treatment was practical and successful in most cases when the fractures involved the bones of the jaws and the face. Fractures which involved the cranial cavity or the cranial nerves were difficult to treat and usually held a poor prognosis. PMID- 4015561 TI - The occurrence, cost and control of sawfly larval (Lophyrotoma interrupta) poisoning of cattle in Queensland 1972-81. AB - A postal survey of cattle producers in the Maranoa, Warrego and Leichhardt districts of Queensland where poisoning of cattle by larvae of the sawfly (Lophyrotoma interrupta) occurs was carried out in 1982 with 179 replies (64% of those contacted). During 1972-81, 50 farms with 84,300 cattle experienced deaths (5254 on 37 farms) during July to September. The worst years were 1975 (955 deaths) and 1979 (1895 deaths). Heavy losses occurred on 9% of farms. These were where the silver-leaved iron bark (Eucalyptus melanophloia) was most common. To prevent the disease, 37 graziers moved cattle from dangerous areas and 52 partly removed E. melanophloia from their farms. 31 fed supplements to try to prevent the pica thought to cause cattle to eat larvae. 53 who had suffered sporadic or no deaths took no action. The survey results indicated that cattle should not be returned to dangerous areas until early October. The estimated total yearly cost from reduced carrying capacity, control measures and deaths was $1,100,000 (1981 values). Improved control by advice on property management and a better knowledge of the population dynamics of the sawfly was suggested. The use of antidotes or toxoids was thought inappropriate. PMID- 4015562 TI - Enzootic pneumonia of pigs in South Australia--factors relating to incidence of disease. AB - Environmental and management conditions of 15 herds with a high-prevalence (greater than 70%) of enzootic pneumonia of pigs at slaughter were compared with 16 herds with a low-prevalence (less than 30%) to determine factors commonly predisposing pigs to enzootic pneumonia in South Australia. Comparisons were made of herds having greater than 100 sows (fully intensive units) and also small herds having 20 to 70 sows (sideline units). Half the herds were visited in summer and half in winter to detect seasonal factors. In small herds, factors commonly found associated with a high prevalence of enzootic pneumonia were larger numbers of pigs per shed section (p less than 0.001), larger group sizes (p less than 0.01) and draughty farrowing and weaner accommodation (p less than 0.01). In large herds, factors associated with a high prevalence were higher pen stocking rate (p less than 0.05) and airspace stocking rate (p greater than 0.05), and a trend toward higher atmospheric ammonia levels in summer (p less than 0.1). PMID- 4015563 TI - Performance following a 500-675 rad neutron pulse. AB - A three-light, three-lever discrete avoidance behavioral task was initiated to study the effects of a 500-675 rad neutron pulse upon performance. Eight primates performed the task for 4 h (3.5 h postexposure) on exposure day and for 4 h on each of 3 d postexposure. For the exposure day, five subjects had a decrease in correct responses, seven had increased reaction times, and six experienced productive emesis within 3.5 hours postexposure. Although the performance degradations were not severe, these data suggest that the performance of time critical tasks could be significantly impaired. PMID- 4015564 TI - The effectiveness of specific weight training regimens on simulated aerial combat maneuvering G tolerance. AB - To assess the effectiveness of muscle-strength (weight training) on simulated aerial combat maneuvering (SACM) G tolerance, seven young men were exposed to a 12-week program of whole-body weight training in which were measured, strengths of various muscle groups, body circumferences, body mass, and the percentage of body fat. The magnitudes of the weights used in training were used to measure muscle strength and were compared and correlated with each subject's SACM tolerance--defined as the total time that a subject could withstand continuous exposure to a 4.5 and 7.0 + Gz centrifuge profile using fatigue as his voluntary endpoint. Chest and biceps circumferences increased 4.2% and 3.1%, respectively; abdomen and thigh circumferences did not significantly change; body fat decreased 16.8%; and body mass increased 2.3%. Abdominal (sit ups) and biceps (arm curl) strengths increased 99% and 26.2%, respectively, and were highly correlated with SACM tolerance time (p less than 0.01); leg (leg press) and chest strengths (bench press) made less significant contributions to the SACM tolerance time. A net increase in SACM tolerance times of 53% resulted from weight-training. Multiple regression analysis of all four muscle groups between weeks 1 and 12 with the SACM tolerance had a correlation of determination of 0.61. PMID- 4015565 TI - Response to muscular exercise following repeated simulated weightlessness. AB - The effect of repeated weightlessness exposures on maximal aerobic capacity was determined when seven healthy men (36-48 yr) underwent two 10-d bedrest (BR) periods in the -6 degrees headdown position, which were separated by a 14-d recovery period. No prescribed exercise was performed by the subjects during the course of the experiment. A graded supine cycle ergometer test consisting of 4 min of unloaded pedaling at 60 rpm followed by increased work rate of 15 W X min 1 until volitional fatigue (max) was performed before (pre) and after (post) the first and second BR periods, i.e., BR1 and BR2, and again 14 d after BR2 (REC). During exercise, submaximal and maximal oxygen uptake (VO2), ventilation (VE), heart rate (HR), systolic (SBP) and diastolic (DBP) blood pressures were measured and the gas exchange anaerobic threshold (AT) was determined. Plasma volume (Vp, T-1824) and body composition were measured pre- and post-BR1 and BR2 and following REC. Compared to the respective pre-BR control values, VO2max decreased (p less than 0.05) by 8.7% after BR1 and 5.2% after BR2 but returned to pre-BR values following 14 d REC. Submaximal and maximal HR increased (p less than 0.05) post-BR1 and BR2 but returned to pre-BR levels after REC. The AT and Vp decreased (p less than 0.05) post-BR1 and BR2 but returned to pre-BR levels after REC. Body weight increased (p less than 0.05) gradually during the experiment and did not return to control values.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4015566 TI - A nationwide survey of civilian air ambulance services. AB - To identify and characterize civilian air ambulance services, a questionnaire was mailed nationwide to 583 prospective air ambulance services, with 154 responding. Our survey identified differences between hospital, hospital-affiliated, and private air ambulance services as to aircraft ownership, availability, types of aircraft, types of patients being transported, types of medical personnel and equipment, aircraft retrofit, and their feelings regarding air ambulance regulations. We found that hospital air ambulances are better suited for transporting critically ill patients while many private air ambulances appear better suited to transport nonemergency patients. Hospital-affiliated air ambulance services, although not as consistent in providing the specialized care of hospital air ambulances, appear better able to provide critical care than private air ambulance services. Based upon this data, we recommend that air ambulance regulations be directed at levels of patient care. Such regulations and guidelines will assist patient safety during aeromedical transports without jeopardizing currently operating air ambulance services. PMID- 4015568 TI - Subjective effects of combined-axis vibration: II. Comparison of X-axis and X plus-pitch vibrations. AB - Seated subjects matched their perceptions of the intensity of single-axis vibrations in the X axis, or combined-axis vibrations made up of X-axis and pitch motions, by adjusting the intensity of a sinusoidal, 5 Hz, Z-axis response vibration. Stimulus vibrations were sinusoidal at 3.15, 4, 5, 6.3 and 8 Hz. For each frequency, both types of vibration were presented at three acceleration levels related to three axis-to-seat distances for the pitch vibrations. Results showed that Z-axis response accelerations were essentially constant across frequency. However, matching responses were significantly higher for X-plus-pitch than for X-axis vibrations. These findings are in contrast to those of a previous experiment involving Y-axis and roll vibrations, and are probably due to additional input from the seat back for X and pitch motions. The two experiments do agree on the importance of the distance of the subject from the axis of rotation for angular motions. In both experiments, as stimulus acceleration (axis to-seat distance) increased, response acceleration increased substantially at every frequency. PMID- 4015567 TI - Age and pilot performance. AB - In military and civilian aviation, pilot age is a major factor which determines if the individual is allowed to continue flying. Many factors, including legal considerations, escalating personnel and training costs, and higher skill levels necessitated by increasing equipment complexity, have generated considerable interest in the development of "age free" criteria to determine continued suitability for aviation duty. Central to this issue is a demonstration that older pilots are not necessarily unsafe pilots. Naval Safety Center data relating mishap rates and causal factors to pilot age are presented and policy implications discussed. Results indicate that there are significant differences in mishap rates and mishap causal factors as a function of age, but these differences are not those which might be expected based on a knowledge of the aging literature. PMID- 4015569 TI - Comparison of the hunting reaction in normals and individuals with Raynaud's disease. AB - Cold-induced vasodilation (CIVD or hunting reaction) was studied in eight subjects with Raynaud's disease, an idiopathic vasospastic disorder of the peripheral vasculature, and in nine normal subjects using 5, 10, 15 +/- 1 degree C water bath immersions of the right middle finger. Differences between Raynaud's and normal subjects were only marginal at 5 degrees C; at 10 degrees C, Raynaud's subjects showed a longer time to the first rise of skin temperature, had lower mean digital skin temperature, and a lower amplitude of their digital skin temperature during CIVD; at 15 degrees C, Raynaud's subjects had a longer time to first rise, lower number of CIVD cycles, and a lower recovery temperature. PMID- 4015570 TI - The Environmental Symptoms Questionnaire in acute mountain sickness. AB - A self-completed questionnaire (modified Environmental Symptoms Questionnaire) was evaluated in a study of acute mountain sickness (AMS). The questionnaire scores for headache, nausea, and the general feeling of ill health correlated well with AMS scores obtained by clinical interview. Modifications in the instructions and the phrasing of some of the questions are suggested and we doubt whether factor analysis provides any better data than more simple statistical methods. The questionnaire is a useful additional method for the assessment of symptoms of AMS. PMID- 4015571 TI - Back to basics: suggested solutions to some flight instruction problems. AB - Since 1976 a series of surveys of flight instructors and students in general and commercial aviation, and the Royal Australian Air Force, has indicated several common problems in flight instruction. These problems have provided a focus for instructor education programs described in this paper. Professional preparation of instructions in areas such as educational psychology (learning and memory, motivation, and skill acquisition) met with the approval of the participants, but no detectable change in instructional methods resulted. It is concluded that a commitment to the professionalization of flight instruction must come from within the occupational group. PMID- 4015572 TI - Transderm scopolamine efficacy related to time of application prior to the onset of motion. AB - We evaluated Transdermal Scopolamine related to the time of application prior to the onset of motion. In this study 44 subjects participated. The first group applied the transdermal disc within 4 h and the second group 8 h or more prior to the onset of motion. We observed a significant decrease in the incidence and the degree of motion sickness for the group with at least 8 h of scopolamine application prior to sea travel. Therefore, the transdermal scopolamine system should be applied at least 8 h before potentially disturbing motion to provide adequate prophylaxis against motion sickness. We found no significant difference in motion sickness susceptibility between men and women, in contrast to earlier reports. PMID- 4015573 TI - Food poisoning as an in-flight safety hazard. AB - The leading cause by far of airline pilot incapacitations is gastrointestinal illness resulting from "food poisoning". This potentially hazardous condition is inadequately dealt with by the airlines today and strikes equally in all pilot age groups. Sufficient incidents are occurring to justify more stringent aircrew meal standards and regulations. Aircrew heart attack and stroke concerns pale into insignificance relative to the far more common food poisoning incapacitations. Specific regulations on aircrew feeding should be promulgated by the Federal Aviation Administration and the regulatory authorities in other countries to preclude simultaneous-onset in-flight incapacitations due to common source food poisoning. PMID- 4015574 TI - Portable air mobile life support unit. AB - The Israeli Air Force Medical Corps has developed a portable Air Mobile Life Support Unit (AMLS) for use in emergency airborne medical evacuations. This unit was designed so that it could be easily moved from one aircraft to another, thus allowing for tactical flexibility and avoiding the necessity for a dedicated ambulance aircraft. The unit is capable of supplying critical care for two patients and supportive care for two less severely injured. Three main functional units comprise the AMLS. These include (1) oxygen ventilation system, (2) cardiac monitoring and defibrillation system, and (3) vacuum pump for aspiration of secretions. Each of these units can be removed and operated independently of the AMLS for field use. Accessories include a control panel, illumination unit and a medical supply cabinet. The AMLS unit may be installed or removed in less than 2 min by two crew men. The AMLS has been operational and successfully used in air evacuations in wartime as well as in peace time. Air Medical crews report that the AMLS has been easily accessed and has operated without any malfunction. PMID- 4015575 TI - Plasmids in bacteria. PMID- 4015576 TI - Control of plasmid replication: theoretical considerations and practical solutions. PMID- 4015577 TI - Conjugal plasmid transfer in Bacillus thuringiensis. PMID- 4015578 TI - Assessment of risk from low-level exposure to radiation and chemicals. A critical overview. PMID- 4015580 TI - The isolation and characterization of the Blym-1 transforming gene. AB - There are a number of similarities between chicken bursal lymphomas and human Burkitt's lymphomas. Both lymphomas are associated with viral infection, by LLV in bursal lymphomas and Epstein-Barr virus in Burkitt's lymphoma. Avian lymphoid leukosis virus integration is associated with enhanced c-myc expression, while the role EBV plays in tumorigenesis remains unclear. In Burkitt's lymphoma, however, c-myc activation does occur as a result of specific chromosomal translocations involving the human c-myc locus. Furthermore, the activated transforming genes detected by transfection of both bursal lymphoma and Burkitt's lymphoma DNAs are homologous members of the Blym family of genes. These similarities between chicken and human lymphomas provide evidence that viral involvement and oncogene activation are significant in tumor development and suggest they are involved in the multi-step progression to the neoplastic phenotype. The function of the Blym genes remains to be determined. Although the chicken and human Blym genes are only distantly related, they have maintained their homology to the amino-terminal regions of transferrins. This fact may reflect some functional constraint on the evolution of these genes. It is therefore possible that transforming genes such as Blym may function via a transferrin-related mechanism. PMID- 4015579 TI - Statistical aspects of the estimation of human risks. AB - The preceding paper has discussed the general problem of high dose to low dose extrapolation within a single animal species. The purpose of this extrapolation is to estimate the effects of low level exposure to toxic agents known to be associated with undesired effects at high dose levels. Mathematical models of dose response are necessary for this extrapolation process since the low dose effects, expected to be on the order of response rates of 10(-6, are too small to be accurately measured with limited study sample sizes. A number of mathematical dose-response models have been proposed for extrapolation purposes; we have shown how similar they can appear to one another in the range of observable response rates, yet how different they become at lower, unobservable response rates, the region of primary interest. This is the single, most important limitation of this extrapolation methodology. An estimate of risk at a particular low dose, or an estimate of the dose leading to a particular level of risk is highly dependent upon the mathematical form of the presumed dose response and differences of 3 - 4 orders of magnitude are not uncommon. Therefore, all these sources of uncertainty, dose-response model, pharmacokinetic behavior of the toxic agent, thresholds, heterogeneity, and patterns of exposure, lead to substantial uncertainties in estimates of risk based on high to low dose extrapolations. PMID- 4015581 TI - Report of National Cancer Institute symposium: comparison of mechanisms of carcinogenesis by radiation and chemical agents. I. Common molecular mechanisms. PMID- 4015582 TI - Quantitative neoplastic transformation in C3H/10T1/2 cells. PMID- 4015583 TI - Risk estimate for genetic effects. PMID- 4015584 TI - Role of tumor promotion in affecting the multi-hit nature of carcinogenesis. AB - The assessment of risk from low-level exposure to radiation and chemicals is hindered by the basic lack of scientific understanding of the complex nature of the multiple levels of protective or synergistic interactions. Radiation and chemicals have the potential of inducing mutations, cell death and altered gene expression. The biological consequences of each of these effects is again complex, since many factors can enhance or mask the effect of a single mutation, cytotoxic or gene modulatory change. Carcinogenesis, representing but one chronic disease state, is a multi-step process, involving the clonal expansion of a single altered cell (that is, the initiation event). Radiation and chemicals appear to contribute to the initiation process by their ability to induce viable mutations. Insufficient theoretical and empirical knowledge precludes a determination of whether mutagenesis and, hence, initiation exhibit a threshold phenomenon. Because of a variety of redundancy mechanisms on the genetic and cellular levels, the physiological impact of a single dysfunctional cell is felt only after it is amplified to a large number (the promotion phase of carcinogenesis). Radiation and chemical-induced cytotoxicity, as well as noncytotoxic chemical induction of mitogenesis, can induce surviving single dysfunctional stem cells to multiply. If during this multiplication of dysfunctional cells, the initiated cells are further exposed chronically to low levels of mutagens, there is an enhanced probability of additional genetic changes. The accumulation of foci of dysfunctional cells can occur in any stem cell population of any tissue. As with mutagens, the existence of threshold levels for promoting conditions and chemicals is still not yet scientifically validated. However, specific examples of the actions of a few promoters does seem to be consistent with that idea. The concepts of initiation and promotion imply the existence of anti-initiation and antipromotion conditions. Together with genetic factors, the complex and unpredictable interactions of radiation and chemicals as initiators, anti-initiators, promoters and antipromoters, defy prospects of an easy means to predict the consequences of exposure to chronic low levels of radiation and chemicals. PMID- 4015585 TI - Genetic and epigenetic aspects of tumor progression and tumor heterogeneity. PMID- 4015586 TI - Epidemiological reservations about risk assessment. PMID- 4015587 TI - Interaction of ionizing radiation and 8-methoxypsoralen photosensitization: some implications for risk assessment. PMID- 4015588 TI - Low-level exposures to chemical carcinogens: mutational end points. PMID- 4015589 TI - Radiogenic neoplasia in the thyroid and mammary clonogens: progress, problems and possibilities. PMID- 4015590 TI - Induction and manifestation of hereditary cataracts. AB - A cataract is an opacity of the lens causing a reduction of visual function. The organogenesis of the lens in various mammals is similar. Therefore, a cataract mutation in mice can be directly compared with cataracts in man. Screening for dominant cataracts in mice was combined with the scoring of specific locus mutations. This combination increases the number of scorable loci, allows the comparison of unselected and selected loci and makes possible a systematic comparison of dominant and recessive mutations. In a combined experiment, dominant cataract and specific locus mutations were scored in the same offspring of mice after treatment of spermatogonia. In radiation experiments the induced frequency of dominant cataracts in spermatogonia was after single exposure 4.5 - 5.5 X 10(-5) mutations/gamete/Gy and for specific locus mutations 1.6 - 2.8 X 10( 5) mutations/locus/Gy. In experiments with ethylnitrosourea (ENU) the induced frequency of dominant cataracts was 0.7 - 1.3 X 10(-5) (mutations/gamete)/(mg ENU/kg body weight) and for specific locus mutations 2.6 - 3.3 X 10(-6) (mutations/locus)/(mg ENU/kg body weight). The radiation-induced mutation rate can be used for the direct estimation of the genetic risk in humans. The genetically significant population dose for 19 000 offspring in Hiroshima and Nagasaki was estimated to be 1.1 X 10(6) man-rem, absorbed at high dose rate. For the 19 000 offspring one would expect less than 1 radiation-induced dominant cataract and a total of 20 - 25 dominant mutations. If the number of dominant and recessive loci are equal one would expect in addition the induction of 250 recessive mutations in this population. Chemically induced dominant cataract mutations could be used to determine the allowable level of exposure for a single compound. The genetically characterized mutations will be an ideal source for studies in the field of developmental genetics. The investigation of alpha-, beta , and gamma-crystallins by electrophoretic methods, the activity determinations of enzymes and the systematic use of cDNA hybridization may lead to an understanding of the genesis of dominant cataracts in mice and man. PMID- 4015591 TI - Extrapolation from large-scale radiation exposures: cancer. AB - Even though much is known about cancer risk associated with exposure to ionizing radiation, societal demands for detailed risk assessment go far beyond our ability to satisfy them according to customary standards of scientific accuracy. Society's requirement, however, is for the best information available, however good it may be, and not necessarily for the definitive solution to the problem posed. Bayesian methods may be useful for presenting incomplete and varied data and informed scientific opinion in a form suitable for use in societal decision making, while at the same time providing a disciplinary framework for incorporating opinion into scientific recommendations. Inferences about individual cases and their relationship to risk of radiation carcinogenesis provide an especially severe test of the completeness of our understanding of the relationship between exposure and risk. This is particularly true with respect to the distribution of excess risk over time following exposure. Recent work suggests that a standard model often used for projection of risk forward in time, the constant relative excess model, may give a surprisingly accurate picture of time to tumor for a number of cancer sites. PMID- 4015592 TI - The feasibility and urgency of monitoring human populations for the genetic effects of radiation: the Hiroshima-Nagasaki experience. PMID- 4015593 TI - Prospects for cellular mutational assays in human populations. PMID- 4015594 TI - Cytogenetic and allied studies in populations exposed to radiations and chemical agents. PMID- 4015595 TI - Report of National Cancer Institute symposium: comparison of mechanisms of carcinogenesis by radiation and chemical agents. II. Cellular and animal models. PMID- 4015596 TI - Where the future? Part I--Round table discussion. PMID- 4015598 TI - The agent carrier and transfer approach to radiobiological responses. PMID- 4015597 TI - Where the future? Part II--Round table discussion. PMID- 4015599 TI - What are we doing when we think we are doing risk analysis? PMID- 4015600 TI - [Experience with Scheel's operation in the treatment of congenital clubfoot]. PMID- 4015601 TI - [Experiences in the rehabilitation of patients with mainly traumatic spinal cord injuries]. PMID- 4015602 TI - [Surgical method in intertrochanteric displacement osteotomy]. PMID- 4015603 TI - [Development of coxarthrosis following intertrochanteric displacement osteotomy as seen in the roentgen film]. PMID- 4015604 TI - [The value of Lindemann's method for the treatment of chronic simple or complicated knee joint instability]. PMID- 4015605 TI - [Complex studies in juvenile osteochondrosis deformans of the hip (Calve-Legg Perthes). II. Roentgen diagnosis studies]. PMID- 4015606 TI - [Sequelae of sickle cell disease for the skeletal system]. PMID- 4015607 TI - [An additional case of an interosseous lipoma of the proximal tibia]. PMID- 4015608 TI - The persistence of phorate and carbofuran in soil and rice plants. AB - The insecticides phorate and carbofuran applied at a range of 1 kg a.i./ha in a field trial against the important rice pest Hydronomidius molitor Faust, the rice root weevil, had largely degraded after 4 and 3 months, respectively, in flooded soil. In rice plants a strong decrease in the content of these insecticides was found three weeks after application. At the time of harvest, the rice plants did not contain any insecticide. PMID- 4015609 TI - Changes in the blood and foetal fluid composition at different stages of gestation in ewes. AB - In 15 West African Dwarf ewes blood and foetal fluid were collected and investigated on the 50th, 100th, and 150th day of gestation in order to determine normal values. The foetal fluid increased in volume and weight from day 50 to day 150. It was clear, colourless, and slightly viscous by day 50, but creamy, more viscous, and mucoid by days 100 and 150. The number of cellular blood components was dependent on the gestational age. The same was found for electrolytes, cholesterol, total proteins, albumins, and globulin in the blood and amniotic fluids. PMID- 4015610 TI - Chromosomal translocation 1/29 in Santa Gertrudis sires. AB - Chromosomal analysis of 38 Holstein, 10 Santa Gertrudis, and 5 Zebu sires revealed for the first time the occurrence of the Robertson translocation in this breed. The importance is stressed of cytogenetic studies for sires. PMID- 4015611 TI - Fertility data from daughters of a Santa Gertrudis bull with chromosomal translocation 1/29. AB - Chromosomal analyses were carried out on 26 daughters of a Santa Gertrudis bull with Robertson translocation. All animals belonged to one herd and were of the same age. 11 of them showed translocation 1/29 associated with the lowest fertility performance. The low fertility of the Santa Gertrudis breed is assumed to be due to chromosome mutation. PMID- 4015612 TI - The influence of season, parity, and duration of lactation on some performance traits of sows indigenous to Nigeria. AB - 120 young sows of less than one year of age and 240 old sows indigenous to Nigeria were randomly subjected to a 2 X 2 X 2 factorial analysis of variance. The results showed that the factors season, parity, and lactation period had no influence on the gestation period and some weaning features, like the number of stillborn piglets per litter and pre-weaning deaths. More piglets were farrowed live by old sows than by the young sows. The litter birth weight, the number of piglets weaned per litter and the number of days to estrous following weaning depended on the season and the lactation length. PMID- 4015613 TI - Characterization of cattle in Nigeria--body measurements. AB - The beef cow breeds Boran, Muturu, and N'Dama, which are widely distributed in southern Nigeria, are described in their phenotypes and their performance characteristics. Body measurements exhibited highly significant differences between the breeds as to body weight, wither height, and body length. The constants are presented for estimating the body weight of these breeds from their heart girth and body length under Nsukka conditions. They can be used for measurements in inches (yielding the body weight in lbs) or in cm (body weight in kg). PMID- 4015614 TI - Electrophoretic analysis of genetic variability in the house fly (Musca domestica L.). AB - Methods are described for the resolution of house fly, Musca domestica L., enzymes by vertical polyacrylamide gel electrophoresis. An electrophoretic survey in Ames, Iowa, of 51 loci distributed among 26 enzyme systems revealed that 40% of the loci are polymorphic. Observed and expected heterozygosities measured at 33 loci were 0.0981 and 0.1148, respectively. A significant deficiency of heterozygotes was noted at certain loci. PMID- 4015615 TI - Linkage of lactate dehydrogenase-2, Ldh-2, in the mouse. AB - An electrophoretically detectable variant of lactate dehydrogenase-2 in Mus musculus has been found and used to locate the structural gene, Ldh-2, on chromosome 6. Gene order and recombination frequencies are estimated as Sig--36.0 +/- 4.8--Lc 21.0 +/- 4.1--Miwh--20.0 +/- 4.0--Ldh-2. PMID- 4015616 TI - Genetic variability of proteins from mitochondria and mitochondrial fractions of mouse organs. AB - Proteins of whole mitochondria from mouse liver and brain and proteins of liver mitochondrial fractions (plasma and rough membrane fraction) were separated by two-dimensional electrophoresis. Protein patterns of two inbred strains of mouse, C57BL/6J and DBA/2J, and of F1 mice of these two strains were studied. The protein patterns obtained from the different mitochondrial materials were analyzed with regard to their protein composition and the genetic variability of proteins (qualitative and quantitative protein variants). Included in this analysis are data previously obtained from the cytosols and plasma membranes of the same organs and mouse strains. The results showed the following. Mitochondria and organelle-free cell components (cytosol and plasma membranes) have only a few percent of their proteins in common, while two organs, liver and brain, reveal up to approximately 50% organ-nonspecific proteins. The frequency of proteins common to solubilized and structure-bound proteins ranges below 20%. Genetic variability in protein amount occurs much more frequently than genetic variability in protein structure. Liver proteins reveal more genetic variants than brain proteins. Proteins solubilized in the cell show more genetic variation than structure-bound proteins. Furthermore, the results show that with regard to the composition and the genetic variability of proteins, liver and brain differ more in their mitochondria than in their cytosol and plasma membranes. PMID- 4015617 TI - Two-dimensional gel electrophoresis of proteins for genetic studies in Douglas fir (Pseudotsuga menziesii). AB - A method of two-dimensional gel electrophoresis of proteins from Douglas fir needles is described. Extraction in the presence of sodium dodecyl sulfate (SDS) and 2-mercaptoethanol followed by heating at 100 degrees C produces reliable two dimensional gels which are convenient for genetic studies. Three genotypes from different geographical origins have been compared: among 225 loci expressed, 22 display regulatory variations and 7 show allelic variations. Thus it is now possible to undertake the genetic study of Douglas fir using this powerful technique. PMID- 4015618 TI - Cell proliferation-associated expression of a recently evolved isozyme of triosephosphate isomerase. AB - An electrophoretically unique, thermolabile isozyme of triosephosphate isomerase (TPI; EC 5.3.1.1) accounts for 10-30% of the enzymatic activity in a range of mitotically active human cells and tissues. This type 2 form (subunit) of human TPI appears in two isozymes, an anodally migrating, relative to the constitutive TPI-1/1 homodimer, TPI-2/2 homodimer and the TPI-1/2 heterodimer with an intermediate mobility. Human cell types expressing the induced isozyme, which is the product of the same structural locus as the constitutive isozyme, include mitogen-stimulated lymphocytes, virally transformed B-lymphoblastoid cells, leukemia-derived T-lymphoblastoid cells, HeLa cells, both normal and transformed fibroblasts, and placental tissue. Extracts of nondividing or terminally differentiated human cells/tissues, such as erythrocytes, striated muscle, peripheral lymphocytes, and platelets, contain high levels of the constitutive TPI-1/1 isozyme but little or undetectable levels of the TPI-1/2 or TPI-2/2 isozyme. The cell division-associated TPI-1/2 and -2/2 isozymes are distinct in electrophoretic mobility from the deamidated forms of the constitutive isozyme. Extracts of dividing gorilla fibroblasts display an isozyme pattern identical to that of proliferating human cells, but various proliferating cells derived from the African green monkey, rabbit, and chicken express only the constitutive isozyme. Thus, expression of the cell division-associated isozyme of TPI is restricted to the hominoids, suggesting a recently evolved modification mechanism which is specifically activated in proliferating cells. PMID- 4015619 TI - Tissue-specific developmental regulation of superoxide dismutase (SOD-1 and SOD 2) activities in genetic strains of mice. AB - The activity levels of CuZn superoxide dismutase (SOD) (SOD-1) and Mn SOD (SOD-2) in liver, kidney, and lung were assessed in newborn and 3-, 10-, 25-, and approximately 70-week-old females from seven genetic strains (BALB/c, Csb, C3H/HeSnJ, C3H/S, C57BL/6J, Swiss-Webster, and 129/ReJ) of mice. Total SOD enzyme activity was high at birth and declined somewhat with old age (approximately 70 weeks) in the liver and increased in both kidney and lung from newborn to 25 weeks. The activity level of SOD-1 was found to be highly variable among strains at different ages in liver, with little change associated with aging in the kidney, and showed a strain-specific increase during aging in the lung. In general, SOD-2 activity was lower than SOD-1 activity in liver and lung but levels of the two forms of this enzyme were similar in the kidney. The SOD-2 activity increased with age with little variation among strains in kidney. The increase in this form of the enzyme with age was relatively small and strain specific in lung and highly variable among strains in the liver. The Csb genotype (acatalasemic) at age approximately 70 weeks showed an exceptionally high SOD-1 activity associated with an exceptionally low SOD-2 activity in the liver. Changes in enzyme activity with age in different tissues associated with differences in activity level among genotypes (of the type reported here for SOD 1 and SOD-2) may be indicative of a complex system of enzyme regulation. Further studies are needed to explain fully the genetic/molecular mechanism(s) for SOD regulation. PMID- 4015621 TI - Localization of genes coding for biochemical traits on the second chromosome of Drosophila imeretensis Sokolov (D. littoralis Meigen). AB - We have investigated 13 alleles of four genes coding for acid phosphatase, alpha- and beta-esterases, and malic enzyme. The genes were localized and their positions regarding the centromere are as follows: Acph-1--centromere--Me--cu--dt -alpha-Est--[Inversion 2t]--beta-Est. The occurrence of crossing over in Drosophila imeretensis males, as well as the tetrameric structure of malic enzyme, was confirmed. PMID- 4015620 TI - Immunological characterization of human acid phosphatase gene products. AB - The immunological cross-reactivity of heterogeneous acid phosphatase isozymes from different human tissues has been studied using monospecific antisera prepared against four homogeneous acid phosphatases. The enzyme characterized as tartrate-inhibitable, prostatic acid phosphatase is also found to be present in leukocytes, kidney, spleen, and placenta. The tartrate-inhibitable (liver) lysosomal enzyme is also found in kidney, fibroblasts, brain, placenta, and spleen, but it is not detectable in erythrocytes and prostate. In several tissues, 10-20% of the tartrate-inhibitable enzyme is not precipitated by any of the antisera used; an exceptionally high amount (54%) of such an enzyme is present in human brain. Antiserum against a low molecular weight tartrate resistant liver enzyme (14 kDa) does not crossreact with the erythrocyte enzyme. (10-20 kDa). All other tissues except placenta, prostate, and fibroblast cells show a cross-reactivity with the 14-kDa acid phosphatase antiserum. Thus, the low molecular weight human liver acid phosphatase is distinct from the erythrocyte enzyme, and there are also at least three different tartrate-inhibitable acid phosphatases in human tissues. Chromosomal assignments have been made for only two of the (at least) five acid phosphatases that are present in adult human tissues. PMID- 4015622 TI - Clinal genetic variation at enzyme loci in bald eagles (Haliaeetus leucocephalus) from the western United States. AB - Five polymorphic enzyme loci of about 50 sampled were discovered in blood extracts of bald eagles from Alaska, Washington, Oregon, and Arizona, representing the first biochemical genetic variation described for the species. All five loci exhibited trends of north-to-south clinal geographic variation in gene frequencies. Gene frequencies at three loci culminated in fixation in the Arizona population, which consists of 12 known breeding pairs. The Arizona birds were maximally heterozygous at the other two loci, suggesting the possibility of maintenance of some clines by natural selection. No significant discontinuities in gene frequencies were observed which correlated with earlier descriptions of two subspecies (northern and southern races) of bald eagles. PMID- 4015623 TI - Solubilization of the alternative oxidase of cuckoo-pint (Arum maculatum) mitochondria. Stimulation by high concentrations of ions and effects of specific inhibitors. AB - Selective solubilization of cyanide- and antimycin-insensitive duroquinol oxidase activity from cuckoo-pint (Arum maculatum) mitochondria was achieved using taurocholate. Inhibitor-sensitivities and water-forming DQH2 (tetramethyl-p hydroquinone, reduced form): O2 stoichiometry were the same for the alternative oxidase of intact Arum mitochondria. Cyanide-insensitive oxidation of DQH2 by intact and solubilized mitochondria was stimulated by up to four-fold by high concentrations of anions high in the Hofmeister series, such as phosphate, sulphate or citrate. Optimal (0.7 M) sodium citrate increased Vmax. for DQH2 oxidation by the solubilized preparation from 450 to 2400 nmol of O2 X min-1 X mg of protein-1 and decreased the apparent Km for DQH2 from 0.53 to 0.38 mM. Inhibition of solubilized DQH2 oxidase activity by CLAM (m-chlorobenzhydroxamic acid) and SHAM (salicylhydroxamic acid) was mixed competitive/non-competitive, with apparent inhibition constants for CLAM of 25 microM (Ki) and 81 microM (KI) and for SHAM of 53 microM (Ki) and 490 microM (KI). Propyl gallate and UHDBT were non-competitive inhibitors with respect to DQH2 (apparent Ki = 0.3 microM and 12 nM respectively). Low concentrations of C18 fatty acids selectively inhibited cyanide-insensitive oxidation by intact and solubilized mitochondria, and inhibition was reversed by 1% (w/v) bovine serum albumin. Inhibition was competitive with DQH2, suggesting that fatty acids interfere reversably with the binding of DQH2 to the oxidase. These results tend to support the view that quinol oxidation by the alternative pathway of Arum maculatum mitochondria is catalysed by a quinol oxidase protein, rather than by a non-enzymic mechanism involving fatty acid peroxidative reaction. [Rustin, Dupont & Lance (1983) Trends Biochem. Sci. 8, 155-157; (1983) Arch. Biochem. Biophys. 225, 630-639]. PMID- 4015624 TI - The inactivation of ornithine transcarbamoylase by N delta-(N'-sulpho diaminophosphinyl)-L-ornithine. AB - Phaseolotoxin, a tripeptide inhibitor of ornithine transcarbamoylase, is a phytotoxin produced by Pseudomonas syringae pv. phaseolicola, the causal agent of halo-blight in beans. In vivo the toxin is cleaved to release N delta-(N'-sulpho diaminophosphinyl)-L-ornithine, the major toxic chemical species present in diseased leaf tissue. This paper reports on the interaction between N delta-(N' sulpho-diaminophosphinyl)-L-ornithine and ornithine transcarbamoylase. N delta (N'-Sulpho-diaminophosphinyl)-L-ornithine was found to be a potent inactivator of the enzyme, in contrast with phaseolotoxin, which previously has been reported to inhibit the enzyme reversibly. Inactivation by N delta-(N'-[35S]sulpho diaminophosphinyl)-L-ornithine resulted in the incorporation of 35S into ethanol precipitated protein. The stoicheiometry of 35S incorporation was approximately 1 mol/mol of active sites. Inactivation was second-order and a rate constant of 10(6) M-1 X s-1 at 0 degree C in 50 mM-Tris/HCl, pH 9.0, was obtained. Carbamoyl phosphate, a substrate of ornithine transcarbamoylase, protected the enzyme from inactivation. A dissociation constant of 3 microM for the enzyme-carbamoyl phosphate complex was calculated. L-Ornithine, the second substrate for ornithine transcarbamoylase, protected the enzyme only at high concentrations. The results are consistent with N delta-(N'-sulpho-diaminophosphinyl)-L-ornithine being a potent affinity label that binds via the carbamoyl phosphate-binding site of ornithine transcarbamoylase. Cleavage of phaseolotoxin to N delta-(N'-sulpho diaminophosphinyl)-L-ornithine in vivo appears to be an important function in the physiology of the disease. PMID- 4015625 TI - A kinetic and equilibrium study of ligand binding to a Root-effect haemoglobin. AB - The blood of the striped marlin (Tetrapturus audax) contains one major Root effect haemoglobin. Titrations of this haemoglobin with CO show that at high pH the molecule is highly co-operative (Hill coefficient 2.8) whereas at low pH the titration data can best be described as the sum of contributions from non-co operating subunits of different affinity. In terms of the two-state model the R state affinity constant is much more sensitive to pH than is that of the T state. Flash-photolysis studies were used to characterize the kinetics of ligand binding to this haemoglobin. Both T and R states show kinetic heterogeneity in their recombination time courses, associated with the alpha- and beta-chains of the molecule. The rate constants for ligand binding to each chain, in each quaternary state, were determined, and in conjunction with the allosteric equilibrium parameters determined at pH8.0 were used in the two-state analysis of reaction curves, over a range of ligand concentration. The two-state model, extended to take account of chain difference, adequately fits the homotrophic effects observed for this haemoglobin. The two-state model is, however, inadequate in its description of the heterotropic effects produced by protons. PMID- 4015626 TI - Studies in vivo and in vitro on the uptake and degradation of soluble collagen alpha 1(I) chains in rat liver endothelial and Kupffer cells. AB - Intravenously administered 125I-labelled monomeric alpha 1 chains (125I-alpha 1) of collagen type I were rapidly cleared and degraded by the liver of rats. Isolation of the liver cells after injection of the label revealed that the uptake per liver endothelial cell equalled the uptake per Kupffer cell, whereas the amount taken up per hepatocyte was negligible. The uptake of 125I-alpha 1 in cultured cells was 10 times higher per liver endothelial cell than per Kupffer cell. The ligand was efficiently degraded by cultures of both cell types. However, spent medium from cultures of Kupffer cells, unlike that from cultures of other cells, contained gelatinolytic activity which degraded 125I-alpha 1. The presence of hyaluronic acid, chondroitin sulphate or mannose/N-acetylglucosamine terminal glycoproteins, which are endocytosed by the liver endothelial cells via specific receptors, did not interfere with binding, uptake or degradation of 125I alpha 1 by these cells. Unlabelled alpha 1 and heat-denatured collagen inhibited the binding to a much greater extent than did native collagen. The presence of fibronectin or F(ab')2 fragments of anti-fibronectin antibodies did not affect the interaction of the liver endothelial cells, or of other types of liver cells, with 125I-alpha 1. The accumulation of fluorescein-labelled heat-denatured collagen in vesicles of cultured liver endothelial cells is evidence that the protein is internalized. Moreover, chloroquine, 5-dimethylaminonaphthalene-1 sulphonylcadaverine (dansylcadaverine), monensin and cytochalasin B, which impede one or more steps of the endocytic process, inhibited the uptake of 125I-alpha 1 by the liver endothelial cells. Leupeptin, an inhibitor of cathepsin B and 'collagenolytic cathepsins', inhibited the intralysosomal degradation of 125I alpha 1, but had no effect on the rate of uptake of the ligand. The current data are interpreted as follows. (1) The ability of the liver endothelial cells and the Kupffer cells to sequester circulating 125I-alpha 1 efficiently may indicate a physiological pathway for the breakdown of connective-tissue collagen. (2) The liver endothelial cells express receptors that specifically recognize and mediate the endocytosis of collagen alpha 1(I) monomers. (3) The receptors also recognize denatured collagen (gelatin). (4) Fibronectin is not involved in the binding of alpha 1 to the receptors. (5) Degradation occurs intralysosomally by leupeptin inhibitable cathepsins. PMID- 4015627 TI - Induction of metallothionein mRNA in rat liver and kidney after copper chloride injection. AB - The kinetics of the increase of metallothionein mRNA in rat liver and kidney after CuCl2 injection was determined by cell-free translation and dot-blot hybridization of total RNA isolated at various times after the injection. Both assay procedures gave essentially the same result: a 16-fold increase in hepatic metallothionein mRNA was observed 7h after CuCl2 injection, with a decline to basal values by 15 h. The response in the kidney was less dramatic, with a 6-fold increase in metallothionein mRNA 5 h after injection, and basal values were attained by 12h. The rise in Cu2+ concentration in both organs was closely correlated with the increase in metallothionein mRNA; hepatic Cu2+ was increased 5.9-fold by 5h after injection and renal Cu2+ was increased 4.3-fold 5h after injection. The Zn2+ concentration in the liver had not risen significantly within 5h of Cu2+ injection. Renal Zn2+ concentrations did not alter appreciably in the Cu2+-treated animals. These results support the conclusion that Cu2+ is acting as a primary inducer of metallothionein mRNA in the rat. PMID- 4015629 TI - Fresh non-fruit latex of Carica papaya contains papain, multiple forms of chymopapain A and papaya proteinase omega. PMID- 4015628 TI - Kinetic studies of the uptake of aspartate aminotransferase and malate dehydrogenase into mitochondria in vitro. AB - Kinetic measurements of the uptake of native mitochondrial aspartate aminotransferase and malate dehydrogenase into mitochondria in vitro were carried out. The uptake of both the enzymes is essentially complete in 1 min and shows saturation characteristics. The rate of uptake of aspartate aminotransferase into mitochondria is decreased by malate dehydrogenase, and vice versa. The inhibition is exerted by isoenzyme remaining outside the mitochondria rather than by isoenzyme that has been imported. The thiol compound beta-mercaptoethanol decreases the rate of uptake of the tested enzymes; inhibition is a result of interaction of beta-mercaptoethanol with the mitochondria and not with the enzymes themselves. The rate of uptake of aspartate aminotransferase is inhibited non-competitively by malate dehydrogenase, but competitively by beta mercaptoethanol. The rate of uptake of malate dehydrogenase is inhibited non competitively by aspartate aminotransferase and by beta-mercaptoethanol. beta Mercaptoethanol prevents the inhibition of the rate of uptake of malate dehydrogenase by aspartate aminotransferase. These results are interpreted in terms of a model system in which the two isoenzymes have separate but interacting binding sites within a receptor in the mitochondrial membrane system. PMID- 4015630 TI - Quantitation of malondialdehyde (MDA) in plasma, by ion-pairing reverse phase high performance liquid chromatography. AB - An ion-pairing high performance liquid chromatography method is described for the separation and quantitation of malondialdehyde in plasma. The MDA is determined as the thiobarbiturate chromogen formed by reaction of the plasma with 2 thiobarbituric acid under acid and heating conditions. However, under these conditions other interfering chromogens can also be formed. Using DEAE-cellulose chromatography followed by ion-pairing HPLC, we have been able to separate and quantitate the levels of MDA-TBA chromogen formed in plasma from other interfering chromogens. Measurements of MDA levels in the plasma of six normal individuals by HPLC gives a mean value of 4.57 +/- 0.33 nmole/ml, whereas the spectrophotometric determined value is 8.83 +/- 1.15 nmole/ml. These data suggest that some reevaluation of the numerous papers published on MDA levels in plasma using spectrophotometric methods may be necessary. PMID- 4015631 TI - Regulation of NAD- and NADP-linked isocitrate dehydrogenase by thyroxine in the brain and liver of female rats of various ages. AB - The specific activity of NAD- and NADP-linked isocitrate dehydrogenase and their regulation by thyroxine in the brain and liver of female rats of various ages were studied with the ultimate goal of better understanding the decreased physiological functioning of the brain and liver during old age. Both thyroidectomy and thyroxine treatment have differential age-dependent effects on the activities of these enzymes in both tissues. The activity of NAD-ICDH decreases whereas both cytoplasmic and mitochondrial NADP-ICDH increase simultaneously following thyroidectomy. Thyroxine administration induces NAD-ICDH and depresses NADP-ICDH. The degree of induction and/or repression is lowest in old rats. These effects of thyroxine are actinomycin D sensitive in both the tissues of rats. PMID- 4015632 TI - The increase of lipid peroxidation in rat adjuvant arthritis and its inhibition by superoxide dismutase. AB - Adjuvant arthritis was induced in rats by the injection of Mycobacterium tuberculosis, and its severity was scored according to the macroscopic findings of the legs, tail, and ears. The average score so obtained was lower in SOD injected rats than in the control group. The depression of albumin/globulin ratio was inhibited significantly in rats treated with 10.0 mg/kg of SOD. The levels of acid phosphatase and beta-glucuronidase were elevated after the administration of an adjuvant, and these lysosomal enzymes showed a remarkable increase in the control rats, while the elevation was inhibited in rats injected with 10.0 mg/kg of SOD. The levels of TBA-reactive substances in the sera and synovia were elevated at 2 weeks after the injection of adjuvant and decreased thereafter. In rats injected with 5.0 mg/kg or 10.0 mg/kg of SOD, the increase in both serum and synovial levels of TBA reactants was inhibited significantly. These observations suggest that the aggravation of adjuvant arthritis may be associated with lipid peroxidation due to superoxide, and that SOD may be beneficial for the treatment of arthritis. PMID- 4015633 TI - Heterogeneity of tissue sterols and glycerolipids in Wolman's disease. PMID- 4015634 TI - A new enzyme-coupled spectrophotometric method for the determination of arginase activity. AB - A spectrophotometric method for the determination of arginase (EC 3.5.3.1) is presented. Arginase is coupled to urease and glutamate dehydrogenase and the decrease in absorbance at 340 nm due to the oxidation of NADPH is followed. The method is rapid, is sensitive, is economical and permits continuous monitoring. The initial velocities were directly proportional to the enzyme concentrations between 0.06 and 0.30 units per 0.5 ml. The Lineweaver-Burk plot yielded positive allosteric behavior for the tetrameric enzyme. The K' and the Hill coefficient, n, calculated from Hill plot were found to be 4.7 mM and 1.26 (r = 1.00), respectively. These values are in good agreement with the literature. PMID- 4015635 TI - Serum concentrations of glucuronidated and sulfated bile acids in children with cholestasis. AB - Serum concentrations of nonglucuronidated-nonsulfated, glucuronidated, and sulfated bile acids in 9 control children and 16 children with cholestasis were quantitated by mass fragmentography. Total bile acid levels in control children were 19.55 +/- 2.78 mumol/liter (mean +/- SEM), and glucuronidated and sulfated bile acids comprised 2.6 +/- 0.5 and 17 +/- 3.1%, respectively. In 9 patients with congenital biliary atrasia, total bile acid levels were 167.34 +/- 11.18 mumole/liter of which 2.1 +/- 0.3% were glucuronidated and 15 +/- 1.4% were sulfated. Lithocholic and 3 beta-hydroxy-5-cholenoic acids, which have hepatotoxic effects, were presented in only small amounts in cholestatic children, and they were almost all glucuronidated or sulfated. The percentages of glucuronidated bile acids in control and cholestatic children were lower than in healthy and cholestatic adults, which may be explained by the lower activity of UDP-glucuronyltransferase in neonatal liver. PMID- 4015636 TI - Effect of clofibrate on peroxisomal and mitochondrial beta-oxidation in chicken liver. AB - The effect of a 0.25% clofibrate diet for 2 weeks on peroxisomal and mitochondrial beta-oxidation in chicken liver was studied. The activities of antimycin antimycin A-insensitive palmitoyl-CoA oxidation (peroxisomal beta oxidation) and carnitine acetyltransferase increased about two-fold. The activities of palmitoyl-CoA-dependent O2 consumption (mitochondrial beta oxidation) and carnitine palmitoyltransferase were also slightly activated by the administration of clofibrate, but not significant. Thus, clofibrate may be a typical drug which activates the peroxisomal beta-oxidation more than the mitochondrial one in various species. The effect of clofibrate on peroxisomal carnitine acetyltransferase was the same as that on the mitochondrial one in chicken liver. Serum lipids were not lowered, but hepatomegaly was observed in the present experiment with chicken. PMID- 4015637 TI - Determination of 3 beta-hydroxy-5-cholenoic acid in serum of hepatobiliary diseases--its glucuronidated and sulfated conjugates. AB - 3 beta-Hydroxy-5-cholenoic acid in the serum of control subjects and 62 patients with various hepatobiliary diseases was quantitated by mass fragmentography after separation into nonglucuronidated-nonsulfated, glucuronidated, and sulfated fractions. Deuterium-labeled deoxycholic acid and its glucuronide and sulfate were used as internal standards. Mean concentrations of total 3 beta-hydroxy-5 cholenoic acid in serum (mumole/liter) were as follows: Control subjects (14), 0.184; obstructive jaundice (15), 6.783; liver cirrhosis, compensated (12), 0.433, and decompensated (12), 1.636; chronic hepatitis (12), 0.241; and acute hepatitis (11), 2.364. Most of the 3 beta-hydroxy-5-cholenoic acid was glucuronidated or sulfated. Only in patients with obstructive jaundice did glucuronidation (60 +/- 14%) exceed sulfation (31 +/- 14%), sulfation exceeding glucuronidation in the others. The UDP-glucuronyltransferase might have different substrate specificities for 3 beta-hydroxy-5-cholenoic acid and other common bile acids, especially in the cholestatic state. PMID- 4015638 TI - Isolation of porcine follicular fluid inhibin of 32K daltons. AB - Purification of ovarian inhibin from porcine follicular fluid was performed by using an bioassay based upon the suppression of spontaneous FSH release from cultured cells of rat anterior pituitary. The presence in the follicular fluid of four molecular forms of inhibin activity corresponding to Mr 100K, 80K, 55K and 32K was revealed by SDS-gel electrophoresis under non-reducing conditions. The smallest inhibin amongst them, named 32K inhibin, eliciting about 70% of the total activity in the follicular fluid, was separated by gel filtration in the presence of 8 M urea. By subsequent ion-exchange chromatography, followed by RP HPLC, 32K inhibin was purified to homogeneity with a 8,000 fold purification factor in a yield of 12%. The purified 32K inhibin was found to comprise two polypeptide subunits (Mr 20K and 13K), linked by disulfide bridges and to specifically suppress the secretion of FSH, but not of LH from the pituitary cells. PMID- 4015639 TI - Direct enzyme transfer from lymphocytes corrects a lysosomal storage disease. AB - Fibroblasts from patients with mannosidosis, the lysosomal storage disease resulting from an inherited deficiency of lysosomal alpha-D-mannosidase (EC 3.2.1.24), accumulate specific mannose-containing oligosaccharides which are characteristic of the disease (1,2). The present study shows that these substances were extensively degraded following transfer of the missing enzyme from normal lymphocytes to mannosidosis fibroblasts on direct contact in tissue culture. Moreover, prolonged correction of the metabolic abnormality of the recipient cells was sustained if contact with fresh donor lymphocytes was periodically renewed. These findings may be highly relevant to lymphocyte function in enzyme replacement therapy by transplantation procedures currently being attempted. PMID- 4015640 TI - Effects of D- and L-thyroxine on the glucocorticoid binding capacity of adult rat liver. AB - Administration of either D- or L-thyroxine (T4) significantly increased the glucocorticoid binding capacity of cytosol of the livers of adrenalectomized adult rats. Administration of up to 0.5 mg/100 g body wt. of L-T4 was more effective than that of D-T4, but higher doses (0.8-3 mg/100 g body wt.) of D-T4 increased the binding capacity markedly to more than that with L-T4. T4- administration did not alter the apparent dissociation constant of glucocorticoid binding proteins for glucocorticoid binding, or their behavior on DEAE-cellulose chromatography either before or after thermal activation (23 degrees C for 40 min). Thus the increased binding capacity seemed to be due to increase in the level of glucocorticoid receptor in rat liver. PMID- 4015641 TI - Chemical modification of carboxyl groups on spinach ferredoxin alters its ability to interact with ferredoxin:NADP reductase. AB - Treatment of spinach ferredoxin with glycine ethyl ester in the presence of a water soluble carbodiimide resulted in the modification of 3-4 carboxyl groups and decreased the ability of ferredoxin to participate in NADP photoreduction by chloroplast membranes by about 80%. The ability of the modified ferredoxin to receive electrons from the reducing side of Photosystem I was relatively unaffected. These findings suggest that the modified ferredoxin is unable to interact with ferredoxin:NADP reductase. This has been verified by demonstration that the modified ferredoxin fails to produce difference spectra typical of a ferredoxin-ferredoxin:NADP reductase complex when added to ferredoxin:NADP reductase. PMID- 4015642 TI - Cardiac substances that influence blood-pressure. II. Potent pressor activity in rat and rabbit atrial muscle. AB - In addition to their natriuretic, diuretic and vasodilator activities, freshly prepared aqueous extracts of either rat or rabbit atrial myocardium were shown to elicit significant increases in the blood-pressure of anaesthetized rats. Small aliquots (0.05 ml) intravenously administered caused a transient rise in mean arterial blood-pressure of up to 20%. Slow infusion of 0.4 ml right atrial extract (corresponding to about one half of a rabbit right atrial lobe) during 90 seconds caused the expected natriuresis and diuresis, together with a sustained elevation in arterial blood-pressure (ca 25%) that returned to normal within 3 minutes. This potent pressor activity could not be detected in ventricular extracts. It was furthermore readily separable from the natriuretic peptides and catecholamines by ultrafiltration. The atrial pressor factor is a small proteolytically unstable molecule (300-1000 dalton). PMID- 4015643 TI - Cysteine conjugate beta-lyase activities in rat kidney cortex: subcellular localization and relationship to the hepatic enzyme. AB - Kidney cortex cysteine conjugate beta-lyase enzymes were characterized using S-(2 benzothiazolyl)-L-cysteine and S-(1,2-dichlorovinyl)-L-cysteine as substrates. The contribution of the hepatic form of cysteine conjugate beta-lyase to renal metabolism of these S-cysteine conjugates is not substantial. No cysteine conjugate beta-lyase activity was found in kidney cortex brush border membrane vesicles. Two cysteine conjugate beta-lyase activities with densities corresponding to the mitochondrial and soluble fractions were separated on Percoll gradients. PMID- 4015644 TI - Effect of calmodulin on the structural state of photoreceptor membranes and rhodopsin-containing phospholipid vesicles. AB - The effect of calmodulin on the order of lipids in rhodopsin-free and rhodopsin containing membranes has been studied using spin-label electron spin resonance methods. Calmodulin, up to 10(-6)M, did not change the measured order of lipids in bilayer membranes containing only rhodopsin. However, for bovine rod outer segment disc membranes, which contain rhodopsin and other proteins, calmodulin induced a significant concentration and temperature dependent increase in the order of the membrane lipids. This suggests that the site of calmodulin binding is remote from rhodopsin itself, and the nature of the binding appears to be a membrane surface phenomenon. PMID- 4015645 TI - Effect of polyamines on hemoglobin and globin chain synthesis. AB - Exposure of reticulocytes to 25 mM spermidine and spermine stimulates the incorporation of 14C leucine into hemoglobin and globin polypeptide chains. These two polyamines stimulate beta chain synthesis to a greater extent than they stimulate alpha chain synthesis, thus resulting in a decreased synthetic alpha/beta globin ratio. Because of the low permeability of the red cell membrane to these polycations, less than 1.0% of extracellular spermidine and spermine accumulate within the erythrocyte, thus these effects occur at intracellular polyamine levels that are physiological. Putrescine progressively decreases hemoglobin synthesis at extracellular concentrations greater than 10 mM without affecting the synthetic alpha/beta ratio. These findings suggest a role for polyamines in the fine tuning of the alpha/beta globin ratio at the translational level. PMID- 4015646 TI - Isoform heterogeneity and lipid affinity of human lymph and plasma apolipoprotein A-IV. AB - We have compared the physical properties and lipid affinity of apolipoprotein A IV isolated from lymph chylomicrons and from lipoprotein-depleted plasma. Lymph and plasma apolipoprotein A-IV demonstrated distinctly different charge properties as assessed by anion exchange chromatography and isoelectric focusing. These differences were not attributable to disparities of amino acid or sialic acid content. Lymph apolipoprotein A-IV displayed a significantly higher affinity than plasma apolipoprotein A-IV for particles of a phospholipid-triglyceride emulsion. We conclude that the charge properties of human lymph and plasma apolipoprotein A-IV may determine conformational states which alter its ability to bind to the surface of lipid particles. PMID- 4015648 TI - Effects of acetylenic and olefinic pyrenes upon cytochrome P-450 dependent benzo[a]pyrene hydroxylase activity in liver microsomes. AB - 1-Ethynylpyrene, trans-, & cis-1-(2-bromovinyl)pyrene, methyl 1-pyrenyl acetylene, and phenyl 1-pyrenyl acetylene are substrates for cytochrome P-450 dependent monooxygenases and also inhibitors of cytochrome P-450 dependent benzo[a]pyrene hydroxylase activities in liver microsomes from 5,6-benzoflavone or phenobarbital pretreated rats. 1-Ethynylpyrene, trans-1-(2-bromovinyl)pyrene, and methyl 1-pyrenyl acetylene cause a mechanism based inhibition (suicide inhibition) of the benzo[a]pyrene hydroxylase activities in microsomes from 5,6 benzoflavone or phenobarbital pretreated rats, while cis-1-(2-bromovinyl)pyrene only causes suicide inhibition of the hydroxylse activities in the 5,6 benzoflavone induced microsomes and phenyl 1-pyrenyl acetylene does not cause a detectable suicide inhibition of these activities in either type of microsome. Incubation with NADPH and 1-ethynylpyrene, trans-, or cis-1-(2-bromovinyl)pyrene causes a loss of the P-450 content in the microsomes from 5,6-benzoflavone or phenobarbital pretreated rats, but incubations with methyl 1-pyrenyl acetylene or phenyl 1-pyrenyl acetylene did not cause a loss of the P-450 content of either microsomal preparation. PMID- 4015647 TI - The [4B-3H] NADH-H2O exchange reaction of the mitochondrial NADH dehydrogenase. AB - The purified mitochondrial NADH dehydrogenase enzyme has been shown to catalyze a rapid [4B-3H] NADH-H2O exchange reaction. When the enzyme is subjected to a single freeze-thaw cycle there is a complete loss of NADH dehydrogenation without a measurable decrease in the [4B-3H] NADH-H2O exchange. Complete loss of the [4B 3H] NADH-H2O exchange follows brief exposure to ultraviolet photoirradiation. The differential sensitivity of the water exchange reaction and the dehydrogenase activity suggests a direct involvement of the enzymes flavin cofactor in the catalysis of the [4B-3H] NADH-H2O exchange. Arylazido-beta-alanyl NAD+ (A3'-0-[3 [N-4-azido-2-nitrophenyl)amino] propionyl]NAD+) is shown to be a potent photodependent inhibitor of the [4B-3H] NADH-H2O exchange activity following photoirradiation with visible light. This is consistent with the observed photodependent inhibition of the dehydrogenase activity by this photoprobe (Chen, S. and Guillory, R.J. (1981) J. Biol. Chem. 256, 8318-8323). PMID- 4015649 TI - Molecular size of histamine H-1 receptor determined by target size analysis. AB - Target size analysis (radiation inactivation) was used to study the molecular size of the histamine H-1 receptor of bovine and human cerebral cortex in the intact membrane-bound state. The H-1 receptor in bovine and human cerebral cortex was found to exist in the membrane as a homogeneous population of the same size (160,000 daltons) in each case. Thus no evidence for the existence of multiple forms of the receptor has been found. PMID- 4015650 TI - Structural studies on Allium cepa L. chromatin: enhanced stability of internucleosome interactions in plant chromatin. AB - The pattern of micrococcal nuclease digestion of chromatin from different organs of Allium cepa has been studied. The DNA from small oligonucleosomes appears to be highly degraded and heterogeneous. In solutions of intermediate ionic strength (0.15 M NaCl) histones H2A and H2B form dimers, however at high salt concentrations (2 M NaCl) they tend to form complexes of higher order, such as tetramers. It is proposed that a correlation exists between the ability of these proteins to form tetramers and the particular stability of internucleosome interactions. PMID- 4015651 TI - Acute effects of tumor-promoting phorbol esters on hepatic intermediary metabolism. AB - In hepatocytes isolated from meal-fed rats, phorbol 12-myristate 13-acetate as well as phorbol 12,13-didecanoate stimulated de novo fatty acid synthesis in a dose-dependent manner. Moreover, phorbol 12-myristate 13-acetate inhibited ketogenesis from exogenous oleate, but slightly enhanced oleate esterification. The stimulation of esterification was more pronounced with endogenously synthesized fatty acids. In hepatocytes from 24h-starved rats a moderate stimulation of gluconeogenesis and ureogenesis was observed with glutamine as substrate. It is concluded that tumor-promoting phorbol esters mimic the short term effects of insulin on hepatic fatty acid metabolism. PMID- 4015652 TI - Synthesis and evaluation of a miniature organic model of chymotrypsin. AB - An artificial chymotrypsin, with all the features of the real chymotrypsin, namely a binding site (from cyclodextrin) attached to a catalytic site containing an imidazolyl group, a carboxylate group and a hydroxyl group, has been synthesized. This artificial chymotrypsin has a molecular weight of only 1,365 while the real enzyme has a molecular weight of 24,800. However, from preliminary measurements, both the real and artificial enzymes have approximately the same catalytic activity (both rate and binding constants). PMID- 4015653 TI - Bromodeoxyuridine treatment of rat liver cells in culture induces an increased metabolic conversion of exogenous ornithine. AB - In the presence of bromodeoxyuridine, rat liver cells show an increased incorporation of radiolabeled ornithine into cellular proteins. This increase was not due to activation of urea cycle enzymes but rather to an increase in metabolism of ornithine. Furthermore, treatment with bromodeoxyuridine changes profoundly and selectively the size of the free amino acid pool in these cells. PMID- 4015654 TI - DNA sequence for cloned cDNA for murine amelogenin reveal the amino acid sequence for enamel-specific protein. AB - Enamel is the unique and highly mineralized extracellular matrix that covers vertebrate teeth. Amelogenin proteins represent the predominate subfamily of gene products found in developing mammalian enamel, and are implicated in the regulation of the formation of the largest hydroxyapatite crystals in the vertebrate body. Previous attempts to isolate, purify and characterize amelogenins extracted from developing matrix have proven difficult. We now have determined the DNA sequence for a cDNA for the 26-kDa class of murine amelogenin and deduced its corresponding amino acid sequence. The murine amino acid sequence is homologous to bovine or porcine amelogenins extracted from developing enamel matrices. However, an additional 10-residues were found at the carboxy terminus of the murine amelogenin. This is the most complete sequence database for amelogenin peptides and the only DNA sequence for enamel specific genes. PMID- 4015655 TI - Role of topological constraints in the all-or-none transition of a globular protein model: theory of the helix-coil transition in doubly crosslinked, coiled coils. AB - Employing a recently developed statistical mechanical theory, the alpha-helix-to random-coil transition in two-chain, coiled coils is shown to possess many of the essential qualitative features of the equilibrium folding process in globular proteins. The role of short vs. long range interactions in stabilizing the native structure is examined. We demonstrate in doubly crosslinked coiled coils how, due to the role of loop entropy, an intrinsically continuous conformational transition evolves into one well approximated by an all-or-none transition. Thus the present work points out the crucial role played by loop entropy in the conformational transition in coiled coils in particular and perhaps in globular proteins in general. PMID- 4015656 TI - Fast atom bombardment-mass spectrometric identification of molecular species of platelet-activating factor produced by stimulated human polymorphonuclear leukocytes. AB - Fast atom bombardment mass spectrometry was used to identify molecular species of platelet-activating factor (PAF) produced by stimulated human neutrophilic polymorphonuclear leukocytes. Normal and reverse-phase high performance liquid chromatography were employed to separate the individual regions with PAF activity prior to mass spectrometric analysis. The following alkyl chain homologs of acetyl glyceryl ether phosphorylcholine (AGEPC) were found: C16:0, C17:0, C18:0 and C18:1. There was also evidence for the presence of the C15:0 homolog, as well as other species which have not yet been identified. PMID- 4015657 TI - Response of hepatic ornithine decarboxylase and polyamine concentration to surgical stress in the rat: evidence for a permissive effect of catecholamines on glucocorticoid action. AB - Laparatomy of the rat dramatically induced hepatic ornithine decarboxylase that reached a peak 4 h after the operation. A similar pattern was shown by putrescine concentration. Spermidine was also enhanced, while spermine maintained unchanged. Administration to the animals of either isoproterenol or glucocorticoids (hydrocortisone or dexamethasone) also caused dramatic elevation of liver ornithine decarboxylase. The effect of isoproterenol, but not that of glucocorticoids, was prevented by previous treatment with propranolol. The beta blockade was unable to prevent the effect of laparatomy on the liver enzyme. This was obtained instead, by depleting the endogenous catecholamines with either alpha-methyl-p-tyrosine or reserpine. Under these conditions, administration of glucocorticoids had no effect on the hepatic enzyme. PMID- 4015658 TI - Monoclonal antibody directed isolation and amino-terminal sequence analysis of phenobarbital induced rat liver cytochromes P-450. AB - Cytochrome P-450 was isolated from liver microsomes of phenobarbital treated rats by an essentially single step immunopurification with a monoclonal antibody (MAb). The amino terminal sequence of the isolated cytochrome P-450 displayed a microheterogeneity of isozymes related to previously identified phenobarbital induced forms, indicating that each of these isozymes possess the MAb-specific epitope. This monoclonal antibody-based approach to isolation and subsequent identification of cytochrome P-450 may serve to classify different isozymes by their content of epitopes that bind to different MAbs. PMID- 4015659 TI - Some characteristics of Ca2+ transport in plant mitochondria. AB - Coupled mitochondria isolated from the white leaves of cabbage (Brassica Oleracea, var. capitata) were inactive in respiration-coupled Ca2+ accumulation, in contrast to mitochondria isolated from etiolated corn (Zea mays) which showed the ability to take up Ca2+ from the medium, although with a much lower activity than liver mitochondria. The addition of corn mitochondria to aerobic medium containing succinate as respiratory substrate and a free Ca2+ concentration of 40 microM resulted in Ca2+ uptake with a decrease in free Ca2+ concentration until a steady state of about 2.0 microM was reached and maintained constant for several minutes. Perturbation of this steady state by the addition of Ca2+ or EGTA was followed by Ca2+ uptake or release, respectively, until the steady state was attained at the original extramitochondrial free Ca2+ concentration. These results indicate that corn but not cabbage mitochondria, as with some animal mitochondria, have the ability to buffer external Ca2+ and may be involved in the maintenance of Ca2+ homeostasis in the cell. PMID- 4015660 TI - Acetaldehyde-dependent oxidation of glutathione catalyzed by rat liver cytosol. AB - We have identified a novel reaction in which acetaldehyde promotes rat hepatic cytosolic catalysis of O2 consumption coupled with glutathione oxidation without apparent release of activated forms of O2. Acetaldehyde is not consumed in the reaction. The reaction (O2 consumption or oxidized glutathione production) is saturable with respect to varying glutathione (K'm congruent to 20-45 microM) but not at high acetaldehyde concentrations. However, activity in the range of acetaldehyde found in liver from alcohol metabolism (10-100 microM) appeared to be saturable (K'm congruent to 25-50 microM). Since neither acetaldehyde dependent glutathione loss nor O2 consumption is detectable in guinea pig hepatic cytosol or hepatic cytosol from selenium-deficient rats, we propose that acetaldehyde interacts with glutathione peroxidase, converting the enzyme into a glutathione oxidase. PMID- 4015661 TI - Effect of esterastin, an acid lipase inhibitor, on the free and esterified cholesterol contents of cultured aortic smooth muscle cells treated with LDL and cholesterol ester liquid crystals. AB - The effects of esterastin, an acid lipase inhibitor, on the free and esterified cholesterol contents of cultured smooth muscle cells from pig aorta were examined. The post-nuclear supernatant fraction of the cell homogenate showed maximum acid cholesterol esterase activity at pH 4.5, and 50% of this activity was inhibited by 0.31 microM esterastin. During a 48 h incubation with esterastin, the esterified cholesterol content of the cells increased to about 13 times that of control cells in the presence of low density lipoprotein and to 7 times that of control cells in the presence of cholesterol oleate liquid crystals. The ratio of esterified to free cholesterol also increased to about 5 times the control value in both conditions. PMID- 4015662 TI - Cytolytic activity of cytotoxin isolated from Indian cobra venom against experimental tumor cells. AB - Cytolytic activity of cytotoxin isolated from the venom of the Indian cobra (Naja naja) on experimental tumor cells was far stronger than that on normal cells such as peritoneal exudate cells, spleen cells, and erythrocytes of the rat. The effect on Yoshida sarcoma cells was temperature-dependent, being stronger at 37 degrees C than at 0 degrees C. Intramolecular disulfide linkages and free amino groups in the cytotoxin molecule were shown to be essential for the lytic action on the cell membrane. Yoshida sarcoma cells treated with 0.1 mM N-ethylmaleimide reduced the cytolytic action of the toxin. Antitumor activity of the cytotoxin toward a Yoshida sarcoma inoculated intraperitoneally into a rat was not observed. PMID- 4015663 TI - Partial purification of the receptor protein essential for import of pre ornithine aminotransferase into mitochondria. AB - The isolated mitochondrial outer membrane fraction strongly inhibits the import of pre-ornithine aminotransferase, but other membranes such as rough microsomes did not. This inhibition seems to be caused by a receptor in the isolated outer membrane which binds competitively pre-ornithine aminotransferase. The mitochondrial outer membrane could be solubilized using detergent. And a receptor for pre-ornithine aminotransferase was partially purified by ammonium sulfate fractionation followed by column chromatography on Sephacryl S-300. Liposomes reconstituted from the partially purified receptor and lecithin could inhibit the import of pre-ornithine aminotransferase into mitochondria and bind the precursor. PMID- 4015664 TI - Effect of intratracheally instilled benzo(a)pyrene on the pulmonary and hepatic drug-metabolizing enzymes in normal and vitamin A deficient rats. AB - The effect of intratracheal instillation of different doses of benzo(a)pyrene (0.1, 1.0 and 2.0 mg) on the drug metabolizing enzymes of lung and liver was analysed in rats fed diet with or without vitamin A for 5-6 weeks. Benzo(a)pyrene exposure at 2.0 mg dose only elevated the level of cytochrome P-450 and b5, and activity of benzopyrene hydroxylase in liver, and extent of increase was similar in normal and vitamin A deficient groups. Contrary to this, pulmonary contents of cytochrome P-450 and b5, and benzopyrene hydroxylase activity increased over control values in both the groups even at lower doses of benzo(a)pyrene. Moreover, their values were higher in vitamin A deficient-treated groups compared to normal-treated controls. Increase in these parameters was greater in lung as compared to increase in liver. NADPH cytochrome C-reductase in lung and liver was not affected either by inducing vitamin A deficiency or exposing these rats further to benzo(a)pyrene. Uridine-diphospho-glucuronosyl-transferase (UDP-GT) activity in normal and vitamin A deficient groups was enhanced following exposure to benzo(a)pyrene both in lung and liver. However, activity of this enzyme remained impaired in vitamin A deficient groups, benzo(a)pyrene exposed or not exposed when compared to respective normal controls. Glutathione S-transferase activity remained unchanged following exposure to benzo(a)pyrene both in lung and liver. The apparent increase in hepatic glutathione S-transferase and decrease in pulmonary glutathione S-transferase activity in vitamin A deficiency was only due to vitamin A deficient status of rats with no further effect of benzo(a)pyrene. PMID- 4015665 TI - Preparation and characterization of antibodies with specificity for the amino terminal tetrapeptide sequence of the platelet-derived connective tissue activating peptide-III. AB - Antisera selectively reactive with the N-terminal tetrapeptide sequence of the platelet-derived connective tissue activating peptide-III mitogen were prepared and characterized. Solid phase synthesized Z-Asn-Leu-Ala-Lys(Z)-OH tetrapeptide representing the N-terminus of the mitogen was used as an immunogen after carbodiimide mediated coupling to methylated bovine serum albumin carrier and subsequent removal of Z groups. Anti-tetrapeptide sera demonstrated cross reactivity to the mitogen but not beta-thromboglobulin, fibroblast growth factor, or epidermal growth factor, and a limited cross-reactivity to parathyroid hormone. The studies indicate that the N-terminal sequence of the mitogen is accessible for binding with antibody and the antitetrapeptide sera provide a reagent for the selective measurement of biologically active mitogen in the presence of structurally similar beta-thrombo-globulin. In addition, computer analysis of amino acid sequences revealed that few proteins contain the Asn-Leu Ala-Lys sequence and of those that do, many are retroviral proteins or transforming polyproteins. PMID- 4015666 TI - Differential lipid peroxidative response of rat liver and lung tissues to glutathione depletion induced in vivo by diethyl maleate: effect of the antioxidant flavonoid (+)-cyanidanol-3. AB - The administration of a single dose of diethyl maleate (DEM) to fed rats elicited a drastic decrease in the content of reduced glutathione (GSH) both in liver and lung tissues after 6 h of treatment. Cellular GSH depletion induced by DEM was accompanied by a marked increase in pulmonary lipid peroxidation which was completely abolished by (+)-cyanidanol-3, without changes in the liver. Superoxide dismutase (SOD) activity remained unchanged in both tissues in this situation. Hepatic and pulmonary GSH depletion induced by a second dose of DEM given 24 h later produced a further increase in lung lipid peroxidation and a diminution of pulmonary SOD activity. In this condition, hepatic lipid peroxidation and SOD activity were not altered. These results indicate that lung and liver tissues exhibit a different lipid peroxidative response to chemically induced GSH depletion. PMID- 4015667 TI - The velocity of the reaction between ornithine decarboxylase and antizyme highly depends on the presence of salt and temperature. AB - Antizyme reversibly inhibits ornithine decarboxylase activity by direct binding to the enzyme. The velocity of the reaction between ornithine decarboxylase and antizyme was markedly accelerated as the concentration of sodium chloride in the medium was increased and as the temperature of incubation was lowered. The equilibrium constant (binding constant) of the reaction between ornithine decarboxylase and antizyme was a little increased by decreasing salt concentrations in the medium and by decreasing the temperature of incubation. PMID- 4015668 TI - Evidence for the existence of a sulfhydryl group in the adenylate cyclase active site. AB - 6-Cloro-9-beta-d-ribofuranosylpurine 5'-triphosphate (CIRTP) and 6-mercapto-9 beta-d-ribofuranosylpurine 5'-triphosphate (SRTP) irreversibly inhibit adenylate cyclase from rat brain. Adenosine 5'-[beta, gamma -imido] triphosphate protects the enzyme against inactivation by CIRTP and SRTP and acts as a competitive inhibitor with respect to ATP with the Ki value 2 X 10(-4) M. Study of the pH dependence of the rate of the enzyme inactivation by CIRTP showed that pK for the group modified by this compound is equal to 7.45. Inactivation is first order with respect to the enzyme; the saturation effect is observed at the increased concentration of CIRTP. The k2 and KI values for irreversible inhibition of brain adenylate cyclase by CIRTP were 0.25 min-1 and 1.9 X 10(-4) M, respectively. Adenylate cyclase inhibition by SRTP is also time-dependent. Partial protection against the enzyme inactivation was observed. Dithiothreitol restores the activity of SRTP-inactivated adenylate cyclase. The results obtained indicate the presence of an -SH group in the purine amino group binding area of the enzyme active site. PMID- 4015669 TI - The effect of thiamine pyrophosphate modification on its coenzyme function in a transketolase-catalyzed reaction. AB - The coenzyme function of TPP analogues: 4'-NH-methyl-TPP,6'-methyl-TPP and 6' methyl-4-nor-TPP has been studied in a transketolase-catalyzed reaction. Their dissociation constants have been found with the aid of the circular dichroism method, and coenzyme activity has been determined in a complete transketolase reaction, involving the substrate-donor and the substrate-acceptor, and also at the intermediate stage (by the alpha-carbanionic intermediate oxidation rate). The coenzyme activity values have been found different and largely dependend on the nature of the substrates used. A possibility of TPP functioning by the "two center mechanism" in a transketolase-catalyzed reaction is discussed. PMID- 4015670 TI - Changes in the triacylglycerol content of mitochondrial membranes during development. AB - The lipid content of mitochondria and mitochondrial membranes isolated from foetal, suckling, and adult rat liver mitochondria were compared. In foetal liver mitochondria triacylglycerol made up 26% of the lipids, while in adult rat liver mitochondria the triacylglycerol content was 7%. Esterified fatty acids originating from non-phospholipid sources amounted to 34% in mitochondrial membranes, and this amount decreased in mitochondrial membranes of adult rat liver to 22%. The concentration of phospholipids in the mitochondrial membranes did not change significantly during development. PMID- 4015671 TI - Inhibition of lipid peroxidation by alpha-tocopherolquinone and alpha tocopherolhydroquinone. AB - The antioxidant effect of alpha-tocopherolquinone and alpha tocopherolhydroquinone was studied in liposomes and rat liver submitochondrial particles. Both alpha-tocopherolquinone and alpha-tocopherolhydroquinone inhibit lipid peroxidation induced by ascorbate/Fe2+ in liposomes and by cumene hydroperoxide in submitochondrial particles. Alpha-tocopherolhydroquinone is much more effective than alpha-tocopherolquinone in inhibiting lipid peroxidation. Submitochondrial particles, depleted of ubiquinones and reincorporated with alpha tocopherolquinone, are protected from lipid peroxidation only in the presence of succinate. Alpha-tocopherolquinone cannot replace endogenous ubiquinones in the respiratory chain function, nevertheless it can be reduced by the mitochondrial respiratory chain substrates, presumably through the reduced ubiquinones. PMID- 4015672 TI - Effects of 17 beta-estradiol and progesterone on intestinal digestive and absorptive functions in ovariectomized rats. AB - The effects of low and high doses of 17 beta-estradiol and progesterone for 2 weeks on intestinal digestive and absorptive functions have been investigated in ovariectomized rats. The uptake of glucose was significantly enhanced following ovariectomy and administration of hormones restored the level of glucose uptake to that observed in sham-operated animals. Neither, the uptake of L-leucine nor calcium was affected after ovariectomy and treatment with the hormones. The activity of alkaline phosphatase (AP) of ileum was significantly elevated with the low and high doses of 17 beta-estradiol but in jejunum only at high doses. Progesterone alone did not alter AP activity but the combination of this hormone and 17 beta-estradiol significantly enhanced the jejunal and ileal AP activities. It seems that activity of AP is mainly under the control of 17 beta-estradiol. The activity of ileal disaccharidases and leucine aminopeptidase were enhanced at high doses of 17 beta-estradiol alone or in combination with progesterone whereas in the jejunum only AP activity was increased significantly. The present study indicates that 17 beta-estradiol plays an important role in regulating the activities of intestinal digestive enzymes and it is the ileal enzymes which are more prone to its action. PMID- 4015673 TI - Proton nuclear magnetic resonance assignments of thyroid hormone and its analogues. AB - 1H NMR data of a series of thyroid hormone analogues, e.g., thyroxine (T4), 3,5,3'-triiodothyronine (T3), 3,3',5'-triiodothyronine (rT3), 3,3' diiodothyronine (3,3'-T2), 3,5-diiodothyronine (3,5-T2), 3',5'-diiodothyronine (3',5'-T2), 3-monoidothyronine (3-T1), 3'-monoiodothyronine (3'-T1), and thyronine (TO) in dimethylsulfoxide (DMSO) have been obtained on a 300 MHz spectrometer. The chemical shift and coupling constant are determined and tabulated for each aromatic proton. The inner tyrosyl ring protons in T4, T3, and 3,5-T2 have downfield chemical shifts with respect to those of the outer phenolic ring protons. Four-bond cross-ring coupling has been observed in all the monoiodinated rings. However, this long-range coupling does not exist in T4, diiodinated on both rings, and T0, containing no iodines on the rings. There is no evidence that at 30 degrees C these iodothyronines have any motional constraint in DMSO solution. In addition to identification of the hormones, the potential use of some characteristic peaks as probes in binding studies is discussed. PMID- 4015674 TI - Specific in vitro and in vivo binding of 3H-raclopride. A potent substituted benzamide drug with high affinity for dopamine D-2 receptors in the rat brain. AB - The substituted benzamide drug raclopride, [((-)-(S)-3,5-dichloro-N-((1-ethyl-2 pyrrolidinyl) methyl)-6-methoxy-salicylamide tartrate; FLA 870(-); A40664] was shown to be a potent and selective antagonist of dopamine D-2 receptors by its high affinity for striatal 3H-spiperone binding sites and low potency to block dopamine stimulated adenylate cyclase in vitro. In vitro studies showed that 3H raclopride binds with a high affinity (KD = 1.2 nM) and a low proportion of non specific binding to rat striatal homogenates. The binding of 3H-raclopride is saturable (Bmax = 23.5 pmoles/g wet wt) and reversible (dissociation half-time = 30 min) with a regional distribution of the specifically bound drug showing the following rank-order: striatum greater than nucleus accumbens greater than olfactory tubercle greater than septum greater than hypothalamus greater than hippocampus greater than frontal cortex. After in vivo administration, 3H raclopride accumulates preferentially in dopamine rich brain areas with approximately 10 times higher levels in the striatum than in the cerebellum, when examined 30 min after injection. The in vivo binding of 3H-raclopride was saturable, reversible and showed a low component of non-specific binding. More than 90% of the drug reached the brain in a non-metabolized form as judged by thin-layer chromatography. Pharmacological analysis of 3H-raclopride binding showed that it could be displaced by dopamine agonists and antagonists but not by serotoninergic or noradrenergic drugs. Taken together, the results suggest that 3H-raclopride labels dopamine D-2 receptors with high specificity in the rat brain both in vitro and in vivo, and thus, that it should be a useful tool in studies of central dopamine D-2 receptors. PMID- 4015675 TI - Cytochrome P-450 dependent metabolic activation of 1-naphthol to naphthoquinones and covalent binding species. AB - 1-Naphthol was metabolised by a fully reconstituted cytochrome P-450 system in the presence of NADPH to methanol-soluble and covalently bound products. The formation of 1,4-naphthoquinone, the major methanol-soluble product at early time points, showed an almost total dependence on cytochrome P-450, NADPH-cytochrome P 450 reductase and NADPH, and to a lesser extent on dilauroylphosphatidylcholine. The metabolism was rapid and detectable levels of 1,4-naphthoquinone were formed within 30 sec. 1,4-Naphthoquinone formation was dependent on the concentration of both cytochrome P-450 (0.05-0.04 microM) and 1-naphthol (5-50 microM). Whereas 1,4-naphthoquinone was the major product observed at early time points, additional products were observed after prolonged incubation. In the absence of NADPH and NADPH-cytochrome P-450 reductase, 1-naphthol was metabolised, in a cumene hydroperoxide- and cytochrome P-450-dependent reaction, to 1,2- and 1,4 naphthoquinone and covalently bound products. Glutathione and ethylenediamine inhibited both the NADPH- and cumene hydroperoxide-dependent formation of covalently bound products. These data show that cytochrome P-450 catalyses the activation of 1-naphthol to naphthoquinone metabolites and covalently bound species, the latter most likely being derived from naphthoquinones. PMID- 4015676 TI - Cytochrome P-450-dependent nicotine oxidation by liver microsomes of guinea pigs. Immunochemical evidence with antibody against phenobarbital-inducible cytochrome P-450. AB - When guinea pigs were treated with phenobarbital (PB), the specific activity of liver microsomal nicotine oxidase increased by 42%. PB-inducible cytochrome P-450 (PB-P-450) was purified to homogeneity from liver microsomes of PB-treated guinea pigs. Purified PB-P-450 catalyzed nicotine oxidation when reconstituted with NADPH-P-450 reductase and phospholipid system. Antibody prepared against the purified PB-P-450 formed single precipitation lines with both purified PB-P-450 and microsomal components in livers of PB-treated guinea pigs, and both precipitation lines fused. The antibody against PB-P-450 strongly inhibited nicotine oxidation in the reconstituted system. The antibody also inhibited liver microsomal nicotine oxidase activities in PB-treated and untreated guinea pigs by about 30% and less than 5% respectively. About 45% of total P-450 in liver microsomes of PB-treated guinea pigs was precipitated by the antibody. These results show that PB-P-450 participates in liver microsomal nicotine oxidation in PB-treated guinea pigs but not in untreated control animals. PMID- 4015677 TI - Selenium and drug metabolism--III. Relation of glutathione-peroxidase and other hepatic enzyme modulations to dietary supplements. AB - Male mice were fed a torula yeast-based diet containing different amounts of added selenium for a period of 4 months. Liver glutathione peroxidase activity assayed with H2O2 showed a logarithmic dependence on dietary selenium with a saturation plateau above 2 ppm Se and an extrapolated zero of 0.02 ppm Se. In contrast, liver selenium content and GSH-Peroxidase activity showed a linear correlation. Glutathione peroxidase activity became undetectable at a liver Se content of about 90 ng Se/g liver wet wt. Thus, about 10% of liver selenium is not related to GSH-Px activity. Five dietary groups were supplemented, respectively, with 0, 0.05, 0.5, 5.0 and 10 ppm Se in the form of Na2SeO3. Some changes in drug metabolism enzymes were observed with the high Se diets. An increase occurred in Non-Se-GSH activity as well as in ethacrynic acid-assayed GSH transferase, these are interpreted as early signs of Se toxicity. The diet containing 0.01 ppm Se with no supplementary Se produced the multiple hepatic enzyme modulations which were previously reported. The animals raised on this very low Se diet had normal hepatic contents of glutathione, alpha-tocopherol, calcium, magnesium, iron, zinc, copper and manganese compared to controls supplemented with 0.5 ppm Se. However, significant changes in the microsomal fatty acid pattern were observed while the total phospholipid content as well as membrane fluidity showed no differences between the two dietary groups. PMID- 4015678 TI - Relationship between stimulated inositol lipid hydrolysis and contractility in guinea-pig visceral longitudinal smooth muscle. AB - Carbamylcholine caused a marked, concentration-dependent stimulation of [3H]Ins P, [3H] InsP2 and to a lesser extent [3H]InsP3 production in guinea-pig longitudinal smooth muscle prelabelled with myo-[3H]inositol. Accumulation of these three inositol phosphates showed differential sensitivity to LiCl. Muscle contraction was apparent at lower concentrations of carbamylcholine. Both responses were mediated via muscarinic-type receptors. An association of inositol phosphate production and contractility was also observed in response to substance P, histamine and noradrenaline, the latter via an alpha-adrenergic mechanism. The Ca2+-channel agonist CGP 28392 failed to stimulate inositol phosphate production despite inducing a contractile response. Carbamylcholine -induced inositol phosphate production persisted in the presence of D600 or Mn2+ despite loss of contractile activity. However, both responses showed a similar, marked dependence on the presence of Ca2+ in the extracellular medium. Mn2+ could restore basal and stimulated inositol phosphate production in low Ca2+ solutions but could not substitute for Ca2+ in restoring contractility. The results suggest that stimulated inositol lipid hydrolysis in longitudinal smooth muscle does not result from Ca2+ entry into the tissue, although the response does depend on the concentration of divalent cations in the extracellular medium. This dependency may be related to the maintenance of membrane potential and possibly phospholipid conformation. PMID- 4015679 TI - Biliary excretion and enterohepatic circulation of 1-nitropyrene metabolites in Fischer-344 rats. AB - 1-Nitropyrene (1-NP), present in diesel engine emissions, is a potent mutagen to bacteria, such as those found in mammalian intestinal tract, which contain nitroreductase enzymes. The purposes of this study were to determine the importance of bile as a route of excretion of 1-NP metabolites and to determine if reabsorption of biliary metabolites required the presence of intestinal bacteria. The bile ducts of male Fischer-344 rats were cannulated, 0.3 or 1.2 mumoles [3H]1-NP was given i.v., and bile, urine, and feces were collected for 24 hr. Biliary excretion accounted for 70 (80%) or 170 (60%) nmoles of [3H]1-NP after the low and high dose, respectively, with half-times for excretion of 1.7 hr +/- 0.3 (+/- S.E.M.) and 3.4 hr +/- 1.6 (+/- S.E.M.). Excretion of [3H]1-NP equivalents in the urine was linearly related to dose, with 6 or 16 nmoles (8%) excreted in 24 hr. At the low dose, more radioactivity appeared in the urine in control rats compared to bile-duct cannulated rats, suggesting that reabsorption of 1-NP metabolites occurred. Pretreatment of rats with orally administered antibiotics prior to i.v. injection of 0.3 mumole [3H]1-NP decreased radioactivity excreted in urine compared to untreated controls, suggesting that intestinal microorganisms may alter the biliary metabolites of 1-NP to facilitate reabsorption. Pretreatment of rats with buthionine sulfoximine, a glutathione depletor, decreased the excretion of certain biliary metabolites, suggesting that they were mercapturic acids of 1-NP metabolites. In summary, the results of these studies indicate that bile was an important route of excretion of nitropyrene metabolites. A portion of the excreted metabolites was reabsorbed from the gut, and this reabsorption required the presence of gut microorganisms. PMID- 4015680 TI - Inhibitory effect of chlorpromazine on bone formation in vivo and in vitro. PMID- 4015681 TI - Inhibition of prostaglandin biosynthesis by the mast-cell-degranulating agent compound 48/80 but not by the mast-cell-degranulating peptide (peptide-401) from bee venom. PMID- 4015682 TI - Interaction of cimetidine and ranitidine with the FAD monooxygenase in pig liver microsomes. PMID- 4015683 TI - Natural occurrence of trans-gamma hydroxycrotonic acid in rat brain. PMID- 4015684 TI - The concentration of cytochrome P-450 in human hepatocyte culture. PMID- 4015685 TI - Uses of molecular volume in biochemical pharmacology. PMID- 4015686 TI - Aromatic amino acid metabolites as potential protein binding inhibitors in human uremic plasma. AB - Decreased binding of aromatic acidic drugs and endogenous metabolites to plasma proteins of patients with severe renal failure appears to be due to accumulation of unknown solutes. Both the warfarin and indole binding sites of albumin, the principal binding protein for these ligands, are affected. We used a large number of endogenous aromatic acids and synthetic congeners as displacers (a) better to characterize the chemical requirements for binding to each site and (b) to derive clues to the chemical structure of the undefined binding inhibitors in uremic plasma. 14C-tryptophan, 14C-warfarin and 14C-salicylate were used as bound ligands. Numerous indoles, quinolines and phenyl derivatives were moderate to strong displacers with several structural correlates. Increasing apolar side chain length enhanced displacing potency. A hydroxyl group at the 5 position of indoles and at the para position of phenyl derivatives severely reduced activity. The two ends of amphophilic molecules showed opposite requirements for displacement of tryptophan: the greater the polarity at the hydrophilic end, the greater the tryptophan displacing potency. Conversely, the greater the total hydrophobic mass of the remainder of the molecule, the more potent the inhibition of binding. The dipeptides l-tryptophyl-l-tryptophan and l-tryptophyl-l phenylalanine were potent displacers. Computer-assisted analysis of warfarin binding in the presence of xanthurenic acid revealed inhibition by a mechanism other than simple competition, probably via a third albumin binding locus. We conclude that decreased binding in uremic plasma is most likely the summation effect of a number of retained aromatic acids, peptides, or both types of ligands. PMID- 4015687 TI - Measurement of the association of cholephylic organic anions with different binding proteins. AB - The binding of the colored cholephylic anions tetrabromosulfonphthalein (BSP), di bromosulfonphthalein (DBSP), indocyanine green (ICG) and thymol blue (ThB) to a number of protein preparations including bovine serum albumin, human serum, rat hepatic cytosol and purified rat liver bilitranslocase has been studied by a direct spectrophotometric method. The experimentation provides extinction coefficients, dissociation constants and number of binding sites for the different complexes between dyes and the various proteins. Data obtained by this technique were in excellent agreement with those obtained on the same samples by ultrafiltration. The data presented indicate that the direct spectrophotometry applied to these dyes is simple, rapid and reproducible, making this the approach of choice during the purification of binding proteins when the binding capacity is the only useful criterion to follow the progress of the procedure. PMID- 4015688 TI - Dependence of dopamine receptor conversion from agonist high- to low-affinity state on temperature and sodium ions. AB - Previous workers found that the anterior pituitary dopamine receptors were inconsistent in converting from their high-affinity state (D2 high) into their low-affinity state (D2 low) for dopamine. We tested, therefore, whether temperature or sodium ion concentration could be factors accounting for such inconsistencies. We found that the proportion of sites which converted depended on the temperature of incubation. No conversion occurred at 4 degrees, despite the presence of guanine nucleotide and sodium ions. At room temperature (20 degrees) guanine nucleotide consistently induced complete conversion in the presence of sodium ions, but gave inconsistent conversion in the absence of sodium ions. At body temperature (37 degrees) guanine nucleotide consistently resulted in complete conversion without requiring sodium ions. PMID- 4015689 TI - Induction of cytochrome P-450 by phenobarbital is mediated at the level of transcription. AB - We have previously shown that the 43-fold induction by phenobarbital of the major phenobarbital-inducible cytochrome P-450 of rat liver microsomal membranes (PB P 450) is mediated by a 20-fold increase in the amount of its mRNA in the cytoplasm. Here we demonstrate that the induction of the mRNA can be almost entirely accounted for by an increase in the rate of transcription of genes coding for PB P-450, and involves little or no change in the rates of processing, transport or degradation of the mRNA. Phenobarbital treatment resulted in no amplification or rearrangement of PB P-450 genes. PMID- 4015690 TI - Inhibition of desmethylimipramine 2-hydroxylation by drugs in human liver microsomes. AB - The 2-hydroxylation of desmethylimipramine (DMI) correlates strongly with the 4 hydroxylation of debrisoquine (D) both in human volunteers and in vitro comparing human liver microsomes from different individuals. D competitively inhibits the 2 hydroxylation of DMI in vitro suggesting that DMI is hydroxylated by the 'debrisoquine hydroxylase' which is under monogenic control in man. We have characterized the effect of drugs on the hydroxylation of DMI in human liver microsomes by measuring the formation of 2-OH-DMI with HPLC using fluorescence detection. Amitriptyline, nortriptyline and metoprolol inhibited the hydroxylation of DMI competitively indicating interaction with the catalytical site for DMI 2-hydroxylation. Antipyrine and amylobarbitone at concentrations similar to their Km-values for metabolism did not inhibit DMI-hydroxylation. Thus, for these compounds there was a good correspondence between the drugs' capacity to inhibit DMI 2-hydroxylation competitively in vitro and their apparent metabolism by the 'debrisoquine hydroxylase' in vivo in man. Thioridazine, chlorpromazine, quinidine and quinine also inhibited DMI-hydroxylation competitively. Thioridazine was an unusually potent inhibitor (apparent inhibition constant Ki = 0.75 microM). Quinidine was also an unusually potent inhibitor (Ki = 0.27 microM) and much more efficient than its isomer quinine (Ki = 12 microM). Theophylline could inhibit DMI hydroxylation but with atypical kinetics. We suggest that this simple DMI in vitro test as well as earlier described inhibition tests with debrisoquine, sparteine and bufuralol can be used to screen if drugs interact with the 'debrisoquine hydroxylase' in human liver. PMID- 4015691 TI - Interactions of cadmium with interstitial tissue of the rat testes. Uptake of cadmium by isolated interstitial cells. AB - Previous studies have shown that the administration of cadmium causes extensive necrosis of the testes and, eventually, a high incidence of interstitial cell tumors. However, the interactions of cadmium with interstitial cells of the testes have not been well defined. Therefore, this study was designed to assess the uptake of cadmium into this potential target cell of cadmium carcinogenesis. Interstitial cells were prepared by collagenase dispersion of decapsulated Wistar rat testes and separated from seminiferous tubules by unit gravity sedimentation. Such preparations showed a high exclusion rate of trypan blue. The interstitial cell preparations were incubated at 33 degrees with various concentrations of cadmium (1.0 to 100 microM) for periods ranging from 0.5 to 60 min. At the end of the incubation, cellular cadmium was separated from cadmium in the media by centrifugation through an oil layer. Initial experiments showed three distinct phases of cadmium influx into interstitial cells, a primary rapid velocity phase (V0; 0 to 1.5 min), a second intermediate velocity phase (V1; 3 to 12 min), and a third low velocity phase (V2; 15 to 60 min). V2 appeared to have both influx and efflux components, as efflux experiments indicated an approximate 20% loss of cadmium from 15 to 60 min. The initial phase was found to be nonsaturable and was not decreased by inclusion of potassium cyanide (1.0 mM), N-ethylmaleimide (1.0 mM), or zinc (100 microM) in the incubation mixture. However, V1 was found to be saturable between 50 and 100 microM cadmium and was substantially decreased by the inclusion of potassium cyanide, N-ethylmaleimide or zinc during incubation. These data suggest that cadmium is taken up into interstitial cells by a transport system that may normally function in zinc uptake and may possibly constitute carrier mediated or active transport. PMID- 4015692 TI - Collagen synthesis and degradation in acutely damaged mouse lung tissue following treatment with prednisolone. AB - Corticosteroids are widely used to treat patients with acute lung damage. Recent work has shown that the administration of 30 mg/kg prednisolone to mice, twice daily on days 1-5 after the induction of lung damage with butylated hydroxytoluene (BHT), results in the development of a more severe fibrotic lesion [J.P. Kehrer, A.J.P. Klein-Szanto, E. M. B. Sorensen, R. Pearlman and M. H. Rosner, Am. Rev. resp. Dis. 130, 256 (1984)]. In the present study, the rate of collagen synthesis in lung tissue from BHT-saline-treated mice was greater than that in lung tissue from oil-treated controls at all days examined. During prednisolone treatment, the rate of pulmonary collagen synthesis was significantly less in tissue from BHT-prednisolone-treated mice compared to BHT saline controls. Two days after steroid treatment was stopped (day 7 after BHT), there was a significant increase in the rate of collagen synthesis in lung tissue from BHT-prednisolone-treated mice compared to tissue from both BHT- and oil treated controls. This increase reached a maximum on day 11 and persisted to day 14 after BHT. The rate of pulmonary non-collagen protein synthesis was inconsistently increased in response to treatments with BHT and/or prednisolone. There was, therefore, a relatively greater increase in the synthesis of collagen. The percentage of total protein synthesis committed to collagen increased from 2% in oil-treated controls to 5% on day 7 after BHT alone and reached a maximum of 7.1% on day 11 in lung tissue from BHT-prednisolone-treated mice. The percentage of newly synthesized collagen that was degraded in lung tissue from BHT prednisolone-treated mice was significantly lower than BHT-saline on days 7 and 11, and lower than oil-prednisolone on day 14. These results show that collagen synthesis was decreased in BHT-damaged mouse lung tissue during short-term, high dose steroid therapy. There was, however, an increase in collagen synthesis and a decrease in the degradation of newly synthesized collagen after steroid therapy was stopped. These changes in collagen metabolism may contribute to the steroid induced enhancement of fibrosis seen in BHT-treated mice. PMID- 4015693 TI - Extracellular pH, transmembrane distribution and cytotoxicity of chlorambucil. AB - The effects of extracellular pH (6.2 to 7.3) on uptake and cytotoxicity of the weak acid anti-tumor drug chlorambucil were investigated. Decreasing extracellular pH from 7.3 to 6.5 had a negligible effect on the intracellular pH of Chinese hamster V79 fibroblasts, thus resulting in the formation of a transmembrane pH gradient (intracellular alkaline). Addition of high concentrations of acetate or bicarbonate partially collapsed the pH gradient. Chlorambucil (pKa = 5.8) behaved as a weak acid with enhanced accumulation and cytotoxicity at extracellular pH less than 7.0. As predicted for a weak acid, partial collapse of the transmembrane pH gradient decreased both uptake and cell killing. Since the interstitial pH of micrometastases and solid tumors of many cancers is low relative to normal tissues, these results have potential implications for both in vitro drug testing and in vivo therapy. PMID- 4015694 TI - Cyclopentenyl cytidine analogue. An inhibitor of cytidine triphosphate synthesis in human colon carcinoma cells. AB - The mechanism of action of the cyclopentenyl analogue of cytidine, cCyd, was investigated in human colon carcinoma cell line HT-29. Upon exposure of cells to 10(-6)M cCyd, cell viability was reduced to 20% of control, whereas cytocidal activity was not present after 2 hr of drug exposure. Cell lethality was partially reversible by Urd, Cyd or dCyd at 10(-6)M cCyd, and fully reversible by these nucleosides at 2.5 X 10(-7)M cCyd. The incorporation of [14C]dThd and [3H]Urd into DNA and RNA was inhibited by 50% by exposure for 2 hr to 2.5 X 10( 7) and 1.5 X 10(-6)M cCyd respectively. Upon 24 hr of drug exposure, the IC50 for RNA synthesis was reduced 2.5-fold, whereas DNA synthesis was almost totally inhibited. cCyd produced a rapid and preferential reduction of CTP synthesis with a half-life of 1 hr at 10(-6)M drug. The IC50 of cCyd for reducing CTP concentrations after 2 hr of drug exposure was 4 X 10(-7)M. Concomitant with the reduction of CTP levels was the inhibition of transcription of rRNA and, to a lesser extent, tRNA, without changes in the processing nucleolar RNA. No changes in the size of DNA were produced following treatment with cCyd. These results indicate that cCyd is a potent and rapid inhibitor of CTP synthesis and that this effect correlates with its cytocidal activity. PMID- 4015695 TI - Inhibition of hepatic microsomal drug metabolism by the calcium channel blockers diltiazem and verapamil. AB - Diltiazem and verapamil were found to be inhibitors of the cytochrome P-450 dependent biotransformation of drugs. Diltiazem and verapamil competitively inhibited the N-demethylation of aminopyrine in hepatic microsomes with Ki values of 100 and 140 microM respectively. Both diltiazem and verapamil were N demethylated themselves by hepatic microsomes with Km values of 62 and 145 microM respectively. Both drugs also interacted directly with cytochrome P-450 as measured by difference spectra. Diltiazem caused a type I spectral change and verapamil caused a reverse type I spectral change. No metabolic intermediate complexes could be demonstrated for either drug. Inhibition also occurred in vivo as both drugs could prolong pentobarbital-induced sleeping times in mice at doses comparable to those used in man. These results suggest that diltiazem and verapamil may have the potential to cause drug interactions involving inhibition of drug biotransformation. PMID- 4015696 TI - New method to detect drug-binding protein in muscle using a fluorescence probe. PMID- 4015697 TI - Effect of 1-beta-D-arabinofuranosyl cytosine and hydroxyurea on the repair of X ray-induced DNA single-strand breaks in human leukemic blasts. PMID- 4015698 TI - Distinctive responses of heart muscle and non-muscle cells to oxygen and glucose deprivation as regards phospholipid fatty acids. PMID- 4015699 TI - Xenobiotic imprinting of hepatic metabolic enzyme systems: effect of neonatal 3 methylcholanthrene administration. PMID- 4015700 TI - Factors influencing drug sulfate and glucuronic acid conjugation rates in isolated rat hepatocytes: significance of preincubation time. PMID- 4015701 TI - Lack of relationship between debrisoquine 4-hydroxylation and other cytochrome P 450 dependent reactions in rat and human liver. AB - The effect of various inhibitors and inducers of cytochrome P-450 on the activity of microsomal debrisoquine 4-hydroxylation (DQH) was investigated in rat liver. DQH was strongly inhibited by SKF 525-A, 7,8-benzoflavone, and metyrapone. Pretreatment of animals with common inducers, such as phenobarbital, 3 methylcholanthrene, the commercial PCB mixture, Clophen A-50, dexamethasone and pregenenolone-16 alpha-carbonitrile did not lead to induction of DQH, while most reference reactions, i.e. aldrin epoxidation, ethylmorphine demethylation, and benzo(a)-pyrene hydroxylation were induced under these conditions. DQH likewise was not induced by pretreatment of animals with the enzyme substrate DQ. The relationship between DQH and other cytochrome P-450 functions was also studied in untreated animals. Both genders of Wistar rats exhibited similar rates of DQH, but different activities of the reference reactions. DQH activity in Wistar females however, was 10 times higher than in females of the DA-strain, whereas the reference activities were similar in both strains. The studies were also extended to human liver. DQH activity in homogenates of various biopsy samples was neither correlated to the activity of aldrin epoxidation nor to AHH activity. The results indicate that DQH in the rat and in man reflects the activity of a cytochrome P-450 species not related to various other known cytochrome P-450 functions. PMID- 4015702 TI - Effect of tetracaine on membrane-bound acetylcholinesterase activity and anilinonaphthalene sulphonate-induced membrane fluorescence. AB - Tetracaine (25-300 microM) reversibly inhibits (in vitro) AChE activity of rat brain synaptosome (4.4-100%) and erythrocyte membrane (3.9-65.2%) in a concentration dependent manner. IC50 values of tetracaine for AChE of synaptosome and erythrocyte membrane are 88 and 200 microM respectively. At sub-inhibitory concentrations (less than or equal to 10 microM) tetracaine activates (8.7-23%) AChE of synaptosome but not of erythrocyte membrane. Lineweaver-Burk plots indicate that tetracaine-induced inhibition of AChE is competitive in nature and Ki value decreases on increasing the concentration (greater than 100 microM) of tetracaine in both synaptosome and erythrocyte membrane. Tetracaine (25-500 microM) produces a concentration dependent increase in 1-anilino-8-naphthalene sulphonate (ANS)-induced relative fluorescence (F470) of both synaptosomal (6.5 102%) and erythrocyte membrane (2.4-53.3%) without shifting their emission maxima (470 nm). Further it is also noted that the quantum yield of F470 of both the membranes increases with the increase of tetracaine concentrations (100-500 microM). These results suggest that the interaction of tetracaine with both the enzyme and its lipid microenvironment may be the cause of inhibition of membrane bound AChE activity. PMID- 4015703 TI - The protective effects of taurine on hypoxia (performed in the absence of glucose) and on reoxygenation (in the presence of glucose) in guinea-pig heart. AB - In isolated guinea-pig heart submitted to hypoxia in the absence of substrate and subsequent reoxygenation 1-20 mM taurine decreases LDH release and ventricular arrhythmias, and the recovery of normal electrical and mechanical activity is increased. The taurine effect is dose-dependent, and is not mimicked by beta alanine. Moreover, taurine reduces the increase in calcium gain of reoxygenated heart. PMID- 4015705 TI - Studies on the mechanism of action of quinone antitumor agents. AB - The presence of a quinone group in the structure of a compound has been shown to produce cell kill and DNA strand breaks by a mechanism involving free radicals and active oxygen species. The ability of the compound to bind to DNA appeared to increase the DNA damage induced and the cytotoxic activity. A new series of model compounds has been used to investigate further the role of the quinone group in the mechanism of action of quinone antitumor agents. Bis(dimethylamino)benzoquinone, which contains a quinone group, produced significant cell kill of L5178Y lymphoblasts and induced concentration-dependent single-strand and double-strand breaks in the DNA of these cells. Benzoquinone dimustard, which possesses a quinone moiety and active alkylating groups, was approximately 2500 times more cycotoxic to L5178Y cells than was bis(dimethylamino)benzoquinone and was approximately 200-fold more active in inducing DNA double-strand breaks than was the quinone agent. Benzoquinone dimustard induced no apparent DNA single-strand breaks, but produced significant DNA cross-linking, a process which interferes with the assay for single-strand breaks. The cell kill produced by both quinone agents was inhibited by catalase, but not by superoxide dismutase. The cytotoxic activity of bis(dimethylamino)benzoquinone and two other quinone model compounds, hydrolyzed benzoquinone mustard and benzoquinone mustard, appeared to correlate with the induction of DNA strand breaks, while there appeared to be no correlation between cell kill and DNA double-strand breaks induced by benzoquinone dimustard. However, the cytotoxicity of benzoquinone dimustard appeared to be related to the cross-linking activity of this agent. These studies have provided additional evidence that the presence of a quinone group in the structure of a compound can result in significant cell kill by a mechanism that appears to involve active oxygen species. Quinone containing agents can induce DNA strand breaks, and this effect is enhanced when the agent is able to bind to DNA. The induction of DNA strand breaks appeared to correlate with cytotoxic activity for bis(dimethylamino)benzoquinone, hydrolyzed benzoquinone mustard and benzoquinone mustard, but not for benzoquinone dimustard, suggesting that the contribution of quinone-induced strand breaks to the overall cytotoxicity of an agent may vary considerably. PMID- 4015704 TI - Vitamin K epoxide reductase activity in the metabolism of epoxides. AB - The importance of vitamin K epoxide reductase for the metabolism of a range of structurally diverse epoxides has been investigated. Vitamin K1 epoxide is reduced by rat liver microsomes at a rate of 0.47 nmoles/g liver/min. The rate of menadione oxide reduction is not significantly higher than the non-enzymatic reduction rate. No measurable reduction of benzo[a]pyrene 4,5-oxide, benzo[a]pyrene 7,8-oxide, phenanthrene 9,10-oxide, styrene 7,8-oxide, and dieldrin has been detected, nor could trichothecene T-2 toxin inhibit reduction of vitamin K1 epoxide. Thus, vitamin K epoxide reductase is very specific for vitamin K1 epoxide. Taking into account the range of structurally diverse epoxides investigated and the high specific activities of microsomal epoxide hydrolase and cytosolic glutathione transferase for these epoxides it may be concluded that vitamin K epoxide reductase, in all likelihood, generally does not significantly contribute to the control of epoxides metabolically formed from xenobiotics. PMID- 4015706 TI - In vitro pigment formation from tryptamine. Role of indole-3-acetaldehyde. AB - The metabolic significance of indole-3-acetaldehyde in the process of in vitro pigment formation from tryptamine in the presence of guinea-pig liver mitochondria was investigated. Among the four type selective MAO inhibitors used, pargyline and deprenyl appear to be more effective in inhibiting pigment formation from tryptamine than serotonin, while in the presence of clorgyline and Lilly 51641, pigment formation from serotonin was preferentially inhibited. Reducing agents like ascorbic acid, cysteine and glutathione were found to block pigment formation significantly. Also, a reduction of pigment formation was noted in the presence of NADH and ethanol but not in the presence of NAD. It was observed that the amount of indole-3-acetaldehyde produced enzymatically from tryptamine under the present experimental conditions is not sufficient to account for the total amount of pigment formed in the standard incubation mixture and the generation of nascent aldehyde has greater contribution in pigment formation than that supplemented to the system exogenously. It appears that indole-3 acetaldehyde, tryptamine and MAO are associated with the process of pigment formation. PMID- 4015707 TI - A study into the effects of 2-acetylaminofluorene on hepatic monooxygenase activities in the chick embryo. AB - 2AAF is a potent inducer of cytochrome P-450 in the chick embryo liver. The induction has been characterized with respect to a range of monooxygenase activities and the regiospecificity of 2AAF hydroxylation. Similarities to the response elicited by both PB and 3MC were noted. 2AAF was rapidly deacetylated by hepatic microsomes prepared from control animals to 2AF, an inhibitor of monooxygenase activity. Metabolites generated in vivo and carried over in vitro might have therefore interfered with the subsequent kinetic analysis. In general terms induction of a unique cytochrome P-450 subform(s) could not be attributed to 2AAF in the chick embryo. The data is discussed with respect to the reported resistance of avian species to the hepatocarcinogenic effects of 2AAF. Two possibilities are highlighted, a diversion of 2AAF to ring hydroxylated metabolites and/or deacetylation of 2AAF. Both effects could reduce carcinogenicity by decreasing the concentration of proximate carcinogen and/or promoter(s). PMID- 4015708 TI - The effect of cholecystokinin octapeptide on rat striatal 3H spiperone binding. AB - In the rat striatum sulphated CCK8 has no significant effect on equilibrium binding of 3H-spiperone but has a considerable, although transient, effect under non-equilibrium conditions. Under non-equilibrium conditions (during the association phase of ligand binding) and at high ligand concentrations (1 nM), CCK8 displaces specific binding and at low ligand concentrations (0.1 nM) CCK8 enhances specific binding. CCK8 has no effect on 3H-spiperone dissociation kinetics. PMID- 4015709 TI - Reduced hepatic uptake of propranolol in rats with acute renal failure. AB - The effect of acute renal failure (ARF) on the hepatic uptake and metabolism of propranolol was investigated in relation to the hepatic clearance of the drug. ARF was induced by the subcutaneous injection of uranyl nitrate to rats. The uptake rate of propranolol in the isolated perfused liver was determined by the multiple-indicator dilution method and was found to decrease from 43.6 +/- 2.0 min-1 (mean +/- S.E.) in control to 29.4 +/- 1.7 min-1 in ARF (P less than 0.001). The recovery fraction of propranolol in effluent venous blood increased about twofold in ARF compared to control (P less than 0.05). The metabolic activity for propranolol was examined using the hepatic microsomal fraction prepared from control and ARF rats. There was no significant difference in the kinetics of oxidative metabolism of propranolol between two groups. These results suggest that the previously reported decrease in the hepatic clearance of propranolol in ARF is due to decreased hepatic uptake of the drug from the blood into the liver cells. PMID- 4015710 TI - Effect of various amounts of selenium on the metabolism of mercuric chloride in mice. AB - Male ddY mice were given one injection of (1) mercury (mercuric chloride) simultaneously with various doses of selenium (sodium selenite), (2) mercury alone, or (3) various doses of selenium alone. The interaction between mercury and selenium in the liver and kidneys at 1, 5, 24, 120, and 240 hr after administration was investigated. The concentrations of mercury in the liver of mice receiving mercury and selenium simultaneously were higher than those after administration of mercury alone, while the concentrations of mercury in the kidney decreased markedly over a 1-120 hr period after administration, depending on the dose of selenium administered simultaneously with mercury. Clearly, selenium had a different effect on the accumulation of mercury in the liver and kidneys. Subcellular distribution studies revealed that mercury and selenium which were administered simultaneously were incorporated into the crude nuclear and mitochondrial fractions as stable complexes. The transport of these complexes to the kidneys seems to be limited. In addition, gel filtration of supernatant fractions of liver and kidney through a Sephadex G-75 column indicated that the proportion of mercury bound to metallothionein fraction decreased depending on the dose of selenium administered simultaneously with the mercury. This reduction was attributed to the decreased synthesis of mercury-thionein due to a reduction in the activity of Hg2+ which results from binding between mercury and selenium in the cells. PMID- 4015711 TI - Hepatic extraction of endogenous inhibitors of drug binding to serum protein in the pregnant rat. AB - Significant decreases in the serum protein binding of a fluorescent dye, 1 anilino-8-naphthalenesulfonate (ANS), and salicylic acid (SA) were observed in pregnant rats compared to that in nonpregnant (control) rats. A significant difference in the serum protein binding of ANS and SA between serum samples taken at the hepatic vein and portal vein or femoral artery was also observed in the pregnant rats, while such a sampling site difference in the serum protein binding was not observed in the control rats. In the pregnant rats the affinity of ANS binding to the primary binding site in the serum from the hepatic vein was approximately 70% higher than that in the case of serum from the portal vein. The hepatic extraction of nonesterified fatty acids (NEFA) was also determined, and the extraction ratios in the control and pregnant rats were 0.55 and 0.31 respectively. We concluded from these findings and other evidence that certain endogenous inhibitors of drug binding to serum protein (such as NEFA), which increase during pregnancy, were extracted efficiently by the liver and that the difference in the serum protein binding of ANS and SA between serum samples taken at the hepatic and portal veins or femoral artery in the pregnant rats may be explained by the hepatic extraction of endogenous inhibitors. Our present results support the previous finding by Chou et. al. [Int. J. Pharm. 18, 217 (1984)] that in pregnant rats the serum protein binding of phenytoin is greater in the hepatic vein than that in the femoral vein. PMID- 4015712 TI - Actinomycin D-associated lesions mimicking DNA-DNA interstrand crosslinks detected by alkaline elution in cultured mammalian cells. AB - Cultured human fibroblasts were exposed to various concentrations of actinomycin D, a DNA intercalating agent, and studied by various alkaline elution techniques for the presence of DNA lesions. DNA-protein crosslinks increased proportionately with increasing actinomycin D, with 1.53 crosslinks/10(6) nucleotides after 5 micrograms/ml exposure. However, in the single-strand DNA break assay, elution of DNA initially increased as expected with increasing actinomycin D but thereafter decreased, with only 0.09 breaks/10(6) nucleotides detected after 25 micrograms/ml exposure, suggesting the presence of DNA crosslinking. A standard alkaline elution assay for DNA-DNA crosslinking was performed, and lesions which mimicked such crosslinks were detected, with a relative crosslink frequency of 2.30 after 5 micrograms/ml exposure. These actinomycin D-associated lesions disappeared when the alkaline elution procedure was modified to include additional proteinase digestion and use of the detergent sodium dodecyl sulfate (SDS) in the elution buffer, suggesting that they represented undigested DNA protein crosslinks or nonspecific protein on the filters inhibiting DNA elution. Greater than ten times as many DNA-protein crosslinks were detected in fibroblasts than the number of single-strand DNA breaks after cellular exposure to actinomycin, even after determining breaks using the modified methodology for decreasing cellular protein interference. The data suggest that the actinomycin DNA complex is associated with the formation of DNA-protein crosslinks which represent lesions other than endonuclease-associated DNA strand scission. PMID- 4015713 TI - In vitro inhibition of animal and higher plants 2,3-oxidosqualene-sterol cyclases by 2-aza-2,3-dihydrosqualene and derivatives, and by other ammonium-containing molecules. AB - 2-Aza-2,3-dihydrosqualene and related molecules, a series of new compounds designed as analogues of the transient carbocationic high energy intermediate, occurring in the oxirane ring opening during the cyclization of 2,3 oxidosqualene, were tested in vitro as inhibitors of the microsomal 2,3 oxidosqualene cyclase of animals (rat liver) and of higher plants (maize, pea). These molecules proved to be good and specific inhibitors for the cyclases of both phyla. The inhibition is due to positively charged species and is sensitive to the steric hindrance around the nitrogen-atom. 4,4,10 beta-Trimethyl-trans decal-3 beta-ol and 4,10 beta-dimethyl-trans-decal-3 beta-ol, which have previously been described (J.A. Nelson et al., J. Am. chem. Soc. 100, 4900 (1978] as inhibitors of the 2,3-oxidosqualene cyclase of chinese hamster ovary cells, were found to be non-competitive inhibitors of the rat liver microsomal enzyme and presented no activity towards the higher plants cyclases. Aza derivatives of these decalines (A. Rahier et al., Phytochemistry, in press), which were aimed to mimic the C-8 carbocationic intermediate occurring during later steps of the 2,3 oxidosqualene cyclization did not inhibit the cyclases. This result underlines the theoretical limitations of the high energy analogues concept in designing enzyme inhibitors. Amongst other molecules tested, 2,3-epiminosqualene was found to be a reversible, non-competitive inhibitor of the cyclases; similarly U18666A was a very potent inhibitor of the microsomal cyclases. In contrast AMO 1618, a known anticholesterolemic agent reported previously to act at the level of the 2,3-oxidosqualene cyclization step, was not found per se to act on the cyclases. PMID- 4015714 TI - A radiochemical assay method for carboxylesterase, and comparison of enzyme activity towards the substrates methyl [1-14C] butyrate and 4-nitrophenyl butyrate. AB - A radiochemical assay for carboxylesterase based on the substrate methyl[1 14C]butyrate is described. The blank value corresponds to 1.04 micrograms (liver) 1.44 mg (plasma) of tissues with the highest and lowest activity respectively, which constitute the sensitivity of the method. The hydrolysis of methyl butyrate and 4-nitrophenyl butyrate by plasma, liver, lung, heart, diaphragm, cerebrum, kidney and duodenum of rat have been compared. The results showed that the two substrates were hydrolysed preferentially by two different groups of the enzyme. The effect of selective esterase inhibitors showed that both groups can be characterized as carboxylesterase, because bis-4-nitrophenyl phosphate inhibits the hydrolysis of both substrates, physostigmine has only a slight effect and EDTA is no inhibitor. The exception is the enzyme in the duodenum which is inhibited by all three inhibitors. The effect of phenobarbital induction and soman treatment on enzyme activity towards the two substrates were similar. Sex difference in the plasma activity towards methyl butyrate, but not 4-nitrophenyl butyrate, indicates that the group of carboxylesterase preferentially hydrolyzing 4-nitrophenyl butyrate may be the most important for the detoxification of soman. PMID- 4015715 TI - Metabolism of tamoxifen and its uterotrophic activity. AB - Tamoxifen is an estrogen agonist in mouse uterus, a partial estrogen agonist/antagonist in rat uterus, and a pure estrogen antagonist in chicken oviduct. Tamoxifen metabolism was examined both in vitro and in vivo to determine if differences in the species response to this drug resulted from the differential formation of metabolites with estrogenic or antiestrogenic activity. Animals were given a subcutaneous injection of [3H]tamoxifen, and 4 or 24 hr later tamoxifen and its metabolites were extracted from tissues and separated by TLC. The profiles of metabolites extracted from the livers of these species were qualitatively similar; the principle metabolite was 4-hydroxytamoxifen, which comprised 27, 14, and 16% of the radioactivity from mouse, rat, and chicken livers, respectively, at 24 hr. Tamoxifen, however, was the principal compound extracted from all three livers. Metabolites extracted from mouse and rat uteri were the same ones obtained from liver, although their abundance (relative to tamoxifen) was much lower in uteri than in liver. Metabolite E and bisphenol, two tamoxifen derivatives that we believed might account for the uterotrophic effect of tamoxifen in the mouse, were found not to be formed in either liver or uterus. Tamoxifen metabolism was also studied in vitro using liver microsomes from these same species; The same metabolites were formed in vitro as in vivo, although their relative abundances were lower in vitro. No clear-cut differences in metabolism were seen that would account for the disparate pharmacological effects of tamoxifen in these species. PMID- 4015716 TI - Possible mechanisms for the agonist actions of tamoxifen and the antagonist actions of MER-25 (ethamoxytriphetol) in the mouse uterus. AB - Experiments were conducted to determine why tamoxifen, a non-steroidal antiestrogen, is uterotrophic in mice, whereas MER-25 (ethamoxytriphetol), a structurally related compound, is antiuterotrophic. Initial experiments indicated that the pituitary was not required for a uterotrophic response in mice to either estradiol (E2), tamoxifen (TAM), or 4-hydroxytamoxifen (4-OH-TAM) MER-25 was not uterotrophic in mice but was capable of completely inhibiting the uterotrophic responses of mice to estrogens (E2) as well as antiestrogens (TAM and 4-OH-TAM); this inhibition was reversible by increasing the dose of the antiestrogen (TAM). The relative binding affinities (RBA) of TAM, 4-OH-TAM, and MER-25 to mouse uterus estrogen receptor (ER) and mouse liver antiestrogen binding sites (AEBS) were compared to determine whether either (or both) of these sites mediate the biological effects of these compounds. E2 is arbitrarily assigned an RBA of 100 for ER; similarly, TAM is assigned an RBA of 100 for AEBS. MER-25 bound to AEBS with an RBA of 8.9 and to ER with an RBA of less than 0.06; in contrast, TAM and 4-OH-TAM bound to AEBS with RBAs of 100 and 53, respectively, and to ER with RBAs of 2 and 131, respectively. Five other compounds that had similar RBAs as MER-25 for AEBs (RBAs in the range 4-9) and for ER (RBAs less than 0.06) were tested for their antiuterotrophic activities in vivo against both estrogen (E2) and antiestrogen (TAM) in ovariectomized mice. None of these compounds were antiuterotrophic against either estradiol or tamoxifen (P less than 0.01), nor were any of the compounds uterotrophic in mice. These data suggest that differences in the biological actions of tamoxifen and MER-25 in mice are not mediated through AEBS and are most likely due to differences in their interactions with ER. PMID- 4015718 TI - Differential inhibition by T-2 toxin of total protein, DNA and isoprenoid synthesis in the culture macrophage cell line J774. PMID- 4015717 TI - Affinity of ligands other than triarylethylenes for liver microsomal antiestrogen binding sites. PMID- 4015719 TI - Adrenergic ligand binding in human serum. PMID- 4015720 TI - Competitive binding of the oximes HI-6 and 2-PAM with regional brain muscarinic receptors. PMID- 4015721 TI - IgG and IgM rheumatoid factor synthesis in rheumatoid synovial membrane cell cultures. AB - The detection of rheumatoid factors (RFs) in synovial membranes and fluids of patients with rheumatoid arthritis (RA) has suggested that local production of these antiimmunoglobulin autoantibodies may have a role in the pathogenesis of synovitis. To quantitate RF synthesis in the rheumatoid synovial membrane, 12 synovial specimens were obtained from patients with seropositive RA, 5 from patients with seronegative RA, and 6 from patients with other arthritides. Single cell suspensions were cultured, and supernatants were analyzed for IgG, IgM, IgG RF, and IgM-RF by solid-phase radioimmunoassays. IgM-RF was detected in all of the 12 seropositive culture supernatants, and IgG-RF was detected in 8 of the 12. Addition of cycloheximide to the cultures resulted in a greater than or equal to 40% decreased in the amount of IgM-RF. A similar decrease in IgG-RF occurred in the 4 cultures in which the largest amounts of IgG-RF were detected. IgM-RF synthesis represented 7.3 +/- 0.7% (mean +/- SEM) of the total IgM produced, and IgG-RF represented 2.6 +/- 1.1% (mean +/- SEM) of the IgG synthesized in those cultures with detectable IgG-RF. Cultures of synovial membrane cells (SMC) from seronegative RA patients or patients with other arthritides did not contain detectable amounts of IgM-RF or IgG-RF. Selective synthesis of RF by seropositive synovium was suggested by the observation that the fractions of synthesized IgM with RF activity were greater in the SMC supernatants than in paired sera in all cases, and the fractions of IgG with RF activity were greater in the SMC supernatants of 3 of the 4 cases in which substantial amounts of IgG-RF were produced. Comparison of the percentages of newly synthesized IgM with RF activity in paired cultures of SMC and peripheral blood mononuclear cells similarly indicated selective synthesis of IgM-RF by the synovium. These results demonstrate active and selective synthesis of both IgG-RF and IgM-RF by seropositive SMC. However, RFs account for only a minor fraction of the total Ig produced. PMID- 4015722 TI - Sex ratio and sibship size in juvenile rheumatoid arthritis kindreds. AB - In a study of sibship size and sex ratio in juvenile rheumatoid arthritis, the anticipated sex ratios, including a marked female predominance in early onset pauciarticular disease and in polyarticular disease, were found. The size of the sibship showed a progressive increase with increasing age of the proband at onset of disease. In addition, the sex ratios of the sibs deviated from expected, among families where the proband's disease was characterized as either early onset pauciarticular or polyarticular in its presentation. PMID- 4015723 TI - Pulmonary involvement in systemic sclerosis (scleroderma). AB - One hundred sixty-five nonsmoking systemic sclerosis patients were evaluated by pulmonary function testing. Restrictive lung disease and an isolated reduction of the diffusing capacity of carbon monoxide were the most frequent abnormalities. Patients with the CREST syndrome (calcinosis, Raynaud's phenomenon, esophageal dysmotility, sclerodactyly, and telangiectasias) had a similar frequency and severity of pulmonary involvement compared with the patients who had diffuse scleroderma. CREST syndrome patients with restrictive lung disease rarely had the anticentromere antibody and had more skin and joint involvement of their hands, compared with other CREST syndrome patients. Dyspnea and rales were most commonly found in patients with restrictive lung disease. Fibrosis, shown on chest radiograph, and pulmonary function abnormalities correlated poorly with each other. Dyspnea was associated with restrictive disease, and rales were more commonly found in patients with fibrosis. Patients with a restrictive abnormality had the worst prognosis, with a 5-year survival rate of 58%, although death from pulmonary causes was uncommon. Comparison of these nonsmoking patients with 137 scleroderma patients who smoked, seen during the same time period, revealed more frequent and severe obstructive changes in smokers. Smoking patients with restrictive lung disease had more severe disease than nonsmoking patients. The single breath diffusing capacity for carbon monoxide was significantly decreased in the patients who smoked compared with the nonsmokers. These data confirm that pulmonary function abnormalities are common in patients with systemic sclerosis including CREST syndrome. Smoking appears to have an additive deleterious effect on pulmonary function and should be strongly discouraged. PMID- 4015724 TI - Cellular immunity to collagen and laminin in scleroderma. AB - Peripheral blood mononuclear cells (PBMC) obtained from scleroderma patients and normal controls were cultured in the presence of types I and IV collagen, intima collagen, laminin, and phytohemagglutinin. PBMC from 9 of 19 patients (47%) demonstrated lymphocyte transformation in response to laminin, and those from 2 of 17 patients (12%) demonstrated reactivity to type IV collagen. None of the patient PBMC were responsive to type I collagen or to intima collagen. Healthy controls failed to demonstrate lymphocyte transformation in response to laminin or collagens. Analysis of clinical data, including age, disease duration, and degree of skin thickening and internal organ involvement, failed to predict the response to laminin or type IV collagen. The significance and disease specificity of this cellular immunity to laminin and, with lower frequency, to type IV collagen, that occurs in some scleroderma patients are unknown. PMID- 4015725 TI - Inspiratory muscle dysfunction and unexplained dyspnea in systemic lupus erythematosus. AB - The role of inspiratory muscle dysfunction in lung volume restriction and unexplained dyspnea was studied in 16 consecutive patients with systemic lupus erythematosus. Maximal mouth inspiratory pressure (PIM) and maximal transdiaphragmatic pressure (Pdi max) were measured. Pdi and its components were determined during quiet breathing. No significant association was found between the activity of the disease, several serologic markers, and the inspiratory muscle dysfunction. No specific anti-skeletal muscle antibody was found in these patients. Significant correlations were found between the degree of dyspnea and PIM (r = -0.69, P less than 0.01) and Pdi max (r = -0.75, P less than 0.001); however, dyspnea did not correlate with specific lung compliance. Vital capacity correlated significantly with the degree of dyspnea (r = -0.813, P less than 0.001) and with Pdi max (r = 0.544, P less than 0.05). No correlation was found between vital capacity and specific lung compliance. We conclude that inspiratory muscle dysfunction can be an important mechanism in the pathogenesis of the lung volume restriction and dyspnea in patients with systemic lupus erythematosus. PMID- 4015726 TI - Antineuronal antibodies in neuropsychiatric systemic lupus erythematosus. AB - The diagnosis of neuropsychiatric systemic lupus erythematosus (NP-SLE) is clinical and one of exclusion. Brain cross-reactive lymphocytotoxins or neuronal antibodies have been proposed as a mechanism underlying NP-SLE. We assessed the clinical relevance of neuronal cell binding antibodies using a standardized clinical definition of NP-SLE. Serum from 54 SLE patients and 77 controls were tested for binding to 3 neuroblastoma and 3 glioblastoma cell lines. Thirty-three SLE patients (61%) fulfilled clinical criteria for the diagnosis of NP-SLE; of these, 55% had serum binding activity to both neuroblastoma and glioblastoma cell lines, compared with 33% of the other SLE patients. When reactivity to neuroblastoma cell lines only was assessed, 43% of NP-SLE patient sera demonstrated binding activity, versus 14% of sera from the remaining SLE patients. Control subjects' reactivity to neuroblastoma cell lines was positive in 12% of sera. Analysis of serum reactivity using non-neuronal cell lines revealed that neuroblastoma, but not glioblastoma, cell binding was specific. NP SLE patients with evidence of diffuse symptomatology had a higher mean titer of neuroblastoma cell line binding than those with focal symptomatology. Using a panel of substrates, one can identify a significant proportion of patients who are independently defined as having NP-SLE, who demonstrate specific serum neuronal antibodies. PMID- 4015727 TI - Influence of the severity and duration of murine antigen-induced arthritis on cartilage proteoglycan synthesis and chondrocyte death. AB - Recent studies have shown that joint inflammation can suppress chondrocyte proteoglycan synthesis and can even kill chondrocytes. In the present study, we investigated the influence of the severity and chronicity of murine antigen induced arthritis on the degree of these toxic effects on chondrocytes. Joint inflammation, quantitated by measurements of 99m technetium pertechnetate uptake, was significantly correlated with the inhibition of proteoglycan synthesis, measured by 35S-sulfate incorporation. Histologic grading of the extent of chondrocyte death on day 28 after arthritis induction correlated best with the degree of inflammation present on day 14. High scores for chondrocyte death were found only in mice with persistent, severe arthritis. Our data indicate that the severity of joint inflammation is a major determinant of the degree of chondrocyte proteoglycan synthesis inhibition, whereas both the severity and chronicity of the inflammation determine chondrocyte killing and, therefore, irreversible joint destruction. PMID- 4015728 TI - Pressure erosions: a pattern of bone resorption in rheumatoid arthritis. PMID- 4015730 TI - [A new synthesis for 14C-labeled penicillamine]. PMID- 4015729 TI - Jaccoud's arthropathy of the knees in systemic lupus erythematosus. PMID- 4015731 TI - [The oxidation behavior of dithranol]. AB - When Dithranol is oxidized in a weakly alkaline buffer by air oxygen one has to discuss two different oxidative pathways. Under homogeneous conditions (dithranol dissolved) the only oxidation product is dithranol-dimer (and subsequently dithranol-brown) whereas under heterogeneous conditions (dithranol suspended) mainly chrysazine (dantron) is produced, which does not alter under the chosen conditions. These circumstances may play an important part in the dithranol therapy of psoriasis. PMID- 4015732 TI - Preparation and properties of ryodipine, an effective antihypertensive agent. AB - A novel effective antihypertensive agent, 2,6-dimethyl-3,5-dimethoxycarbonyl-4-(o difluoromethoxyphenyl++ +)-1,4-dihydropyridine (ryodipine, PP-1466) has been obtained. A method for ryosidine synthesis has been developed, side products of PP-1466 synthesis have been isolated and identified. Special characteristics (IRS, UVS, NMR, MS) and chromatography data (TLC, HPLC) are cited. PMID- 4015733 TI - Pharmacological and toxicological properties of ryodipine. AB - 2,6-Dimethyl-3,5-dimethoxycarbonyl-4-(o-difluoromethoxy-p hen yl)-1,4 dihydropyridine (ryodipine, PP-1466) causes lasting decrease in systolic and diastolic arterial pressure at intravenous and oral administration to anesthetized animals. In conscious rats with DOCA-salt (des-oxycortone) and spontaneous hypertension, as well as in rats with hypertension provoked by method of cellophane perinephritis, PP-1466 (1 and 10 mg/kg, orally) decreases systolic pressure considerably. Therapeutic doses of PP-1466 do not essentially affect rhythm and frequency of cardiac contractions. High doses of the drug increase the heart rate. PP-1466 increases coronary blood flow. PP-1466 antagonizes considerably the pressor effect of angiotensin. In this respect PP-1466 is superior to SKF-24260 (2,6-dimethyl-3,5-diethoxycarbonyl-4-(o difluoromethylphenyl)-1, 4-dihydropyridine). PP-1466 reduces hypotensive reaction and tachycardia induced by isoprenaline administration, inhibits decrease in arterial pressure caused by electric stimulation of the vagus nerve and administration of acetylcholine. Hypotension caused by PP-1466 and its negative inotropic effect can be antagonized with calcium chloride. In mice and rats PP 1466 at doses exceeding 10 mg/kg exerts a certain dose dependent depressant effect on the CNS. More protracted depressant effect on the CNS is exerted by nifedipine which was studied parallelly. In rabbits oral PP-1466 decreases in EEG basic rhythm amplitude both in cortical and subcortical structures. High doses of the drug lead to dysrhythmia in bioelectric activity. Acute, subacute and chronic toxicity studies in mice, rats and dogs show that PP-1466 possesses low acute toxicity and is well tolerated at protracted repeated administration of therapeutic and several times higher doses. PMID- 4015734 TI - Pharmacological studies of a newly synthetized 1,4-dihydropyridine derivative, 2,6-dimethyl-3,5-dimethoxycarbonyl-4- (o-difluoromethoxyphenyl)-1,4 dihydropyridine (PP-1466). AB - Hemodynamic effects of a new 1,4-dihydropyridine derivative, 2,6-dimethyl-3,5 dimethoxycarbonyl-4-(o-difluoromethoxyphenyl++ +)-1,4-dihydropyridine (PP-1466), were examined by measuring systemic blood pressure, various arterial blood flow such as femoral, vertebral, renal and superior mesenteric artery, heart rate and respiratory rate in anesthetized dogs. Cardiohemodynamic effects were examined by measuring cardiac output, coronary blood flow, maximal rate of rise of left ventricular pressure (dp/dt max.) and right atrial pressure. The changes in myocardial oxygen consumption associated with the parameters mentioned above were also examined by measuring coronary sinus outflow and oxygen content in blood samples. The results obtained are as follows: The intraarterial administration of PP-1466 to the femoral artery caused vasodilating response. The vasodilating effect of PP-1466 was approximately 200 times more potent than that of papaverine and comparable to that of nifedipine or nicardipine (YC-93). The effective dose to induce vasodilation on femoral, vertebral and superior mesenteric artery by the systemic use of PP-1466 was more than 0.3 microgram/kg i.v. and more than 0.03 mg/kg i.d. The vasodilation in vertebral artery was most prominent. After intravenous administration of PP-1466, renal blood flow decreased probably due to the fall in systemic blood pressure, whereas the flow progressively increased after intraduodenal administration. The effective dose to induce a fall in systemic blood pressure by PP-1466 was the range from 1 to 3 micrograms/kg i.v. and more than 0.1 mg/kg i.d., respectively. Diastolic hypotension was remarkable. Heart rate and respiratory rate were increased at the same time.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4015735 TI - Calcium antagonistic properties of nicardipine, a dihydropyridine derivative assessed in isolated cerebral arteries and cardiac muscle. AB - Calcium antagonistic properties of nicardipine (YC-93), a 1,4-dihydropyridine derivative, were studied in isolated cerebral artery and cardiac tissues of rabbits and dogs. Calcium antagonism was assessed in electrically stimulated rabbit basilar artery. Nicardipine at 10(-7) mol/l shifted to the right the dose response curve for Ca of the phasic contraction evoked by electrical stimulation with an alternating current, and at higher concentration it reduced the maximum tension and slope of the dose-response curve. Nicardipine inhibited the augmented contraction produced by high K, k-strophanthin and 5-hydroxytryptamine. It also caused dose-dependent inhibition of 45Ca uptake enhanced by 80 mmol/l K in dog basilar artery, and had a slight effect on the resting 45Ca uptake. In rabbit basilar artery treated with saponin, nicardipine in a dose of 10(-5) mol/l had no apparent effect on the increase in tension induced by excess Ca. Nicardipine had negative inotropic and chronotropic actions. These results suggest that nicardipine, like nifedipine, has a relative high vascular selectivity, and primarily acts by inhibiting Ca influx through the plasma membrane of vascular and cardiac tissues. PMID- 4015736 TI - Induction of cytochrome P-450 isozymes in liver microsomes of rats treated with the cardiotonic agent sulmazole. AB - Pretreatment of adult male rats with sulmazole (AR-L 115 BS) results in a 2-6 fold increase of the liver microsomal scoparone O-demethylation and 7 ethoxycoumarin O-deethylation activity. The change in the ratio of the demethylation products scopoletin to isoscopoletin from 1 : 1.8 +/- 0.1 in control microsomes to 1: 2.5 +/- 0.1 in microsomes from sulmazole pretreated rats is statistically significant. Sulmazole produces a modified type II difference spectrum when added to microsomes of control or sulmazole-pretreated rats. Immunoquantitation of seven cytochromes P-450 showed that two forms, namely P-450 beta NF/ISF-G and P-450 beta NF-B, are increased 3-4-fold in the microsomes of sulmazole-pretreated rats. PMID- 4015737 TI - Influence of N-acetylcysteine on the hexachlorobenzene induced porphyria in rats. AB - The course of hexachlorobenzene (HCB) induced porphyria was not influenced by the concomitant administration of N-acetylcysteine (NAC) to the animals: urinary excretion of total porphyrins and porphyrin precursors as well as the hepatic aminolevulinate synthase activities were not influenced by NAC treatment. In addition, no differences could be shown between the HCB and the HCB/NAC combination group concerning the hepatic cytochrome P-450 contents or the P-450 dependent enzyme activities. PMID- 4015738 TI - Pharmacological profile of 1-methylsulphonyl-3-(1-methyl-5-nitro-2-imidazolyl)-2 imidazolidinone (Go-10213), a new antiprotozoal agent, in comparison with metronidazole. AB - A new antiprotozoal agent, 1-methylsulphonyl-3-(1-methyl-5-nitro-2-imidazolyl)-2 imidazolidinone (Go-10213) has a distinct advantage over metronidazole when their respective neuropharmacological effects on central and peripheral nervous functions are compared in different animal species. The results show that at equivalent dosage schedules with repeated high dosages, Go-10213 is devoid of adverse central and peripheral neural effects in monkeys; cats and dogs, whereas unequivocal evidence of metronidazole neurotoxicity was obtained in all the three species. Go-10213 compares favourably with metronidazole in animal tests for cardiovascular tolerability. PMID- 4015739 TI - [Comparative study of the bioavailability and pharmacokinetics of isosorbide dinitrate formulations in retard form and in standard preparations by determination of isosorbide-5-mononitrate]. AB - The aim of the study was to determine the relative bioavailability and the pharmacokinetic parameters following administration of a slow-release formulation of isosorbide dinitrate (ISDN, Isdin) capsules (20, 40 and 60 mg). A gas chromatographic method was used to determine the plasma concentrations of ISDN and isosorbide-5-mononitrate (IS-5-MN). All of the required pharmacokinetic parameters were ascertained. The study was performed on 12 healthy volunteers in a steady-state crossover design. A comparison of the areas under the plasma concentration/time curves of the test preparations and the commercial preparations showed higher values for the test preparations in all of the investigations. However, these values were only statistically significant for the 40 and 60 mg formulations ISDN and the 60 mg formulation IS-5-MN. PMID- 4015740 TI - Pharmacokinetics and tolerability of suprofen. Experience with intramuscular application in healthy volunteers. AB - In the present randomized single-blind study local and systemic tolerability of alpha-methyl-4-(2-thienylcarbonyl)-phenyl acetic acid (suprofen, Suprol) 200 mg/ml i.m. were compared with those of diclofenac 25 mg/ml and placebo. The three treatment groups consisted of 15 patients each and were homogeneous with respect to demographic parameters. The volunteers were assigned to these groups in random fashion and underwent treatment with 3 injections/day of either suprofen or diclofenac or placebo for 7 days. Mild local pain or systemic intolerance signs were equally rare in all three groups. The laboratory tests with the three preparations studied failed to indicate any negative influence on the hematopoietic organs or the adrenal activity. Abnormal changes in the ECG and the cardiovascular parameters during the treatment were not observed. Moderately or slightly elevated SGOT and SGPT values were seen during treatment with suprofen; however, these values returned to normal after the treatment. As compared with these elevations the values for subjects on diclofenac were higher and did not return to normal within 5 days following withdrawal of the drug. Moreover, the creatine phosphokinase activity, observed in both the suprofen and the diclofenac group, was so extremely high in subjects on diclofenac that this drug had to extremely high in subjects on diclofenac that this drug had to be withdrawn on day 4 of the study. On the basis of these results it can be stated that intramuscular injections of suprofen 200 mg/ml are locally and systemically well tolerated even on administration t.i.d. Measurement of the steady-state plasma level was not indicative of altered kinetic behaviour of suprofen. The plasma levels remained constant.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4015741 TI - Local and systemic tolerability of suprofen. Experience with intravenous administration and infusion in healthy volunteers (1st comm.). AB - Local and systemic tolerability of alpha-methyl-4-(2-thienylcarbonyl)-phenyl acetic acid (suprofen, Suprol 200 mg/ml intravenous injection and suprofen 200 mg/ml infusion were in the present single-blind crossover study assessed and compared with those of placebo i.v. 12 volunteers each were in random fashion assigned to one of the three treatment groups; for a period of 7 days the subjects received daily 2 intravenous injections or infusions of suprofen or placebo, respectively. Investigator and patients appreciation of local tolerability revealed that no pain or discomfort occurred in 98% of the subjects on suprofen and in 100% of those on placebo. The incidence of limited, moderate or mild, adverse reactions was in the suprofen group higher than in the placebo group. The laboratory tests for the treatment groups indicated no negative effects on either the hematopoietic organs or the liver function; no abnormal changes in ECG and cardiovascular parameters were observed during the treatment period. Tests of the renal parameters, i.e., creatinine clearance, creatinine, and urea (BUN), revealed negative shifts in the first two parameters, whereas BUN remained uninfluenced. On the basis of these results it can be stated that 200 mg/ml of suprofen, given either as intravenous injection or as infusion, were both locally and systemically well tolerated even on administration b.i.d. The more or less unfavorable shifts in the renal parameters, which occurred with placebo as well as with suprofen, require further investigation. PMID- 4015742 TI - Local and systemic tolerability of suprofen. Experience with intravenous administration and infusion in healthy volunteers (2nd comm.). AB - 12 healthy male volunteers who had given consent to the study each received in a randomized cross-over design 13 applications of 2-methyl-4-(2-thienylcarbonyl) phenyl acetic acid (suprofen, Suprol) injection solution 200 mg/ml at 8 a.m. and at 2 p.m. as i.v. bolus injections or as infusions. It could be demonstrated, that suprofen given as multiple dose i.v. bolus injections or as multiple infusion doses was well tolerated. The peak plasma concentrations after i.v. bolus injections were in the range of 16.3 to 42.3 micrograms/ml (mean 26.5) and after 2 h between 1.3 and 9.8 micrograms/ml (mean 3.2). 1.5 h after the start of infusion (end of the infusion) the plasma concentrations were in the range of 4.0 and 11.2 micrograms/ml (mean 7.2) with a infusion rate of 4.6 mg/min for the first 30 min and then of 1.1 mg/min for about 57 additional min. At 2.5 h after the infusion applications the mean plasma level was 2.0 micrograms/ml. There was no indication of accumulation nor accelerated elimination during the 7-day period. There was no statistically significant difference between the plasma elimination after the last injection of the 7-day period and the plasma elimination after i.v. single injection as well as from the elimination after the last infusion of the 7-day period. PMID- 4015743 TI - [The clinical pharmacokinetics of allopurinol. 1. Allopurinol absorption sites and dose proportionality of allopurinol/oxipurinol bioavailability]. AB - The rate and extent of allopurinol absorption was studied following its oral ingestion in a "high frequency capsule" which allows the evaluation of the sites of drug absorption. If allopurinol is liberated in the duodenum or upper jejunum its absorption is fast and complete while its liberation in the lower jejunum results in a slow and incomplete absorption. A capacity limited absorption process for allopurinol, suggested from the results of a study on the allopurinol bioavailability from different formulations, could not be proved in the range of single doses between 200 and 600 mg resp. 2.2 to 12.8 mg/kg. AUC- and Cp-values of allopurinol and oxipurinol correspond to the calculated figures in relation to the different doses/kg. PMID- 4015744 TI - [HPLC determination of troxerutin in plasma and urine following oral administration in man]. AB - A high-performance liquid chromatographic method (HPLC) is described for the analysis of 3',4',7-tri-O-(beta-hydroxy-ethyl)-rutoside (troxerutin) in human plasma and urine. After separation of interfering substances on XAD-2 trihydroxyethylrutoside is converted to tetrahydroxyethylrutoside by 2 chlorethanol in alkaline medium. After HPLC-separation tetrahydroxyethylrutoside is quantified by fluorescence detection. The pharmacokinetics of troxerutin were measured in plasma after oral administration to man. The relative bioavailability of the drug from Venelbin was 97.8 +/- 37.1% compared to an aqueous standard solution. PMID- 4015745 TI - [Antibacterial antibodies in immunoglobulins]. PMID- 4015746 TI - Minority deaf students: an overview. PMID- 4015747 TI - Clinical management of communicatively handicapped minority language populations. PMID- 4015748 TI - The effects of dietary omega-3 polyunsaturated fatty acids on erythrocyte membrane phospholipids, erythrocyte deformability and blood viscosity in healthy volunteers. AB - We have examined, in normal subjects, the effects of a daily dietary supplement of fish oil concentrate ('maxEPA'), providing 3 g of omega-3 fatty acids, on erythrocyte membrane phospholipids, erythrocyte deformability and blood viscosity. After 3 weeks, incorporation of C20:5 omega 3 into erythrocyte phosphatidyl choline (PC) was greater compared to phosphatidyl ethanolamine (PE) and phosphatidyl serine (PS). After 6 weeks, there was no further increase in total erythrocyte C20:5 omega 3, but its distribution amongst phospholipid subclasses had changed. C20:5 omega 3 had increased further in PE and PS, but decreased in PC. Incorporation of C20:5 omega 3 also occurred into PC, PE and PS. omega-3 Fatty acids were incorporated almost entirely at the expense of C18:2 omega 6, but total unsaturation of phospholipids was increased. This is consistent with increased lipid fluidity, which may be an important determinant of erythrocyte deformability. The same dosage of maxEPA also resulted in a significant increase in erythrocyte deformability and a concomitant reduction in whole blood viscosity. Since plasma viscosity and haematocrit were unchanged it seems likely that the effects on blood rheology were mediated by changes in erythrocyte lipid fluidity. Modification of blood rheology by dietary omega-3 fatty acids is of potential value in the treatment of vascular disease. PMID- 4015749 TI - Increased atherosclerosis in rabbits immunized with endothelial cells. AB - Rabbits maintained on normal ration or cholesterol-supplemented diet were immunized with homogenates of endothelial cells grown in cultures that were derived from either bovine or human aorta. Minimal aortic lesions were found in all groups of rabbits fed regular diet; microscopically, differences were seen that manifested as medial lesions in controls and intimal lesions in animals immunized with endothelial cells. Aortic atherosclerosis was significantly increased in the immunized, cholesterol-fed animals over that in controls. This difference was more pronounced in the abdominal aorta where the area with lesions in immunized rabbits was 4-7 times that of controls; atherosclerosis of the thoracic aorta was 2.5-5 times greater in the immunized animals (P less than 0.001 for both segments). Increased atherosclerosis was observed despite a significant reduction in plasma cholesterol in the immunized rabbits (770 +/- 119 mg/dl) compared to controls (1595 +/- 225 mg/dl) (P less than 0.001). Immunization with endothelial cells elicited strong cell-mediated and humoral responses as determined by dermal delayed hypersensitivity and solid-phase immunoradiometric tests, respectively. Cross-reactivity in both assays was found against human and bovine cells. Enhancement of atherosclerosis appears to depend not on induction of immune complexes but on specific antibodies and cell-mediated reactions. PMID- 4015750 TI - Intramural stress as a causative factor in atherosclerotic lesions of the aortic valve. AB - Topographic distribution of atherosclerotic lesions of the aortic valve was investigated in rabbits on a 2%-cholesterol-enriched diet and related to distribution of intramural stress in the valve. Initially the lesions appeared at the base of the leaflet on the aortic face and with time spread further out into the leaflet and up the wall of the aortic sinus. In the leaflet, the lesion occurred only in the pressure-bearing part and was primarily composed of a mass of foam cells. By 10 weeks primary fatty plaques were still confined to the aortic face but fibroblasts within the leaflet had also taken up fat. Even after 33 weeks, the atheromatous plaque had not spread beyond the pressure-bearing part of the leaflet. From silicone rubber casts of the valve it was observed that only part of the leaflet was under pressure and the remaining leaflet sustained no pressure gradient. The maximum intramural stress occurred during diastole on the pressure-bearing part. In systole, the blood flow produced shear stress on the entire leaflet. Hence, occurrence of atherosclerotic lesions only in the area of maximum intramural stress suggests that intramural stress and not shear stress plays an important role in accelerating the process of atherosclerosis. PMID- 4015751 TI - Clinical and rheological studies in patients with intermittent claudication. AB - While the resistance to flow offered by means of arterial narrowing and the collateral arteries are the major determinants affecting peripheral flow, there may be a contribution by those elements which affect the viscosity of the blood. To evaluate these factors, haematocrit, red blood cell aggregation and plasma viscosity were measured in 100 patients with occlusive arterial disease of the lower extremities. Disturbances in these parameters were noted and appeared to be related to the severity and extent of the occlusive disease. However, whether these factors contribute to the cause of intermittent claudication remains uncertain. PMID- 4015752 TI - Influx of [3H,14C]cholesterol-labelled lipoprotein into re-endothelialized and de endothelialized areas of ballooned aortas in normal-fed and cholesterol-fed rabbits. AB - The entry of [3H]- and [3H,14C]cholesterol-labelled lipoprotein into de endothelialized and re-endothelialized areas of balloon-injured rabbit aortas was studied in normal-fed and cholesterol-fed rabbits. Studies were carried out 11-15 weeks after the initial injury when endothelial regeneration involved approximately half of the aortic area. The entry into the aorta of 3H-labelled free and ester cholesterol in lipoprotein over a 72-h period was studied following the ingestion of a single dose of 3H-labelled cholesterol. The entry of double labelled [3H,14C]cholesterol-labelled lipoprotein was also studied over a 6-h period following the injection of plasma from donor rabbits. The accumulation of cholesterol and cholesterol ester in the aorta in both the normal- and cholesterol-fed rabbits was significantly greater for the re-endothelialized (white) areas than for the de-endothelialized (blue) areas or the sham-operated aortas. Where the rabbits were cholesterol-fed 4-10 times the amount of cholesterol accumulated in re-endothelialized intima compared to normal intima. Both entry (micrograms/day/100 mg wet weight aortic intima) and clearance (mu 1 plasma/day/cm2) of free and ester cholesterol were increased in the neointima compared with the normal intima for both normal-fed and cholesterol-fed rabbits. Hydrolysis of cholesterol ester occurred in the neointima and was greater than in the corresponding de-endothelialized area but less than for the sham-operated intima. Synthesis of cholesterol ester was minimal in all areas. Removal of labelled cholesterol and cholesterol ester from the intima during a 20-h efflux period following the initial 72-h loading period indicated that for aortas of both normal-fed and cholesterol-fed rabbits, there was greater removal for normal intima than for either re-endothelialized or de-endothelialized intima. However, no clear difference between the blue and white areas was observed. It is concluded that the accumulation of cholesterol in neointima after balloon injury is associated with a marked increase in permeability to lipoprotein of the neointima as well as to possible binding of lipoprotein to glycosaminoglycan in the artery. PMID- 4015754 TI - Plasma pyridoxal-5-phosphate level as risk index for coronary artery disease. AB - Preliminary evidence is presented that plasma pyridoxal-5-phosphate levels are considerably and significantly reduced (P less than 0.0001) in patients suffering from myocardial infarction when compared to a healthy control group. PMID- 4015753 TI - Plasma carnitine and lipid-lowering drugs. AB - Oral carnitine has been reported to have a lipid-lowering effect with concomitant elevation of high density lipoprotein cholesterol (HDL-C) levels in normo- and hyperlipidemic individuals. Unexpectedly, basal carnitine concentrations were found to be abnormally high in subjects receiving a combination of probucol (1 g/day) and clofibrate (2 g/day), and who also had reduced HDL-C levels. Changes in plasma carnitine levels were found to correlate with clofibrate therapy and to be readily reversible with cessation of this drug. These increases of circulating carnitine were not accompanied by a rise in HDL-C. PMID- 4015755 TI - Alcohol and work: 'policies' are not enough. PMID- 4015756 TI - Prevention: potential at the local level. PMID- 4015757 TI - Alcohol and the chest radiograph. PMID- 4015758 TI - Age-related differences in blood ethanol parameters and subjective feelings of intoxication in healthy men. AB - Healthy men within 4 age groups, 20-29, 30-39, 40-49 and 50-59 years (N = 12 per group), drank 0.68 g/kg ethanol as neat whisky after fasting overnight. The drink was finished within 20 min and the concentrations of ethanol in capillary blood were determined at 30-60 min intervals for 7 hr. At the time of blood sampling, the men were asked to estimate their feelings of intoxication according to an arbitrary scale on which the score 10 indicated 'tipsy' or a 'little high'. The time course of blood ethanol concentration was similar in all 4 groups with the curve for 50-59-year-old men on the highest level and 20-29-year-old men lowest. Subjective intoxication scores were significantly less in the youngest age group and the maximum score for each subject was correlated with age (r = 0.45, P less than 0.01). Total body water (TBW) was not correlated with age directly (r = 0.17, P greater than 0.05) but when it was expressed as percent of body weight a strong negative correlation was found (r = -0.77, P less than 0.001). The mean total body water estimated from ethanol dilution was 46.7 +/- 4.1 l. (+/- SD, N = 48) and this corresponds to 58% of mean body weight of the men. The distribution volume of ethanol/kg body weight (Vd) decreased with ageing (r = -0.59, P less than 0.001) being 0.72, 0.71, 0.68 and 0.66 l/kg on average in the 20-29, 30-39, 40-49 and 50-59-year-old age groups respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4015759 TI - The incidence of alcohol withdrawal symptoms in admissions to the Withington Hospital Detoxification Unit. PMID- 4015760 TI - Assessment of genetic predisposition to alcoholism in male alcoholics. AB - Association between the history of alcoholism in different relatives with the development of alcoholism in male probands was analysed using the rate of development of alcoholism as a marker of genetic predisposition. It was found that a history of alcoholism in parents, grandparents and siblings of parents was associated with an accelerated rate in the development of alcoholism while a history of alcoholism in siblings and children of probands was not. The rate of development of alcoholism was positively associated with the number of generations of the proband's family in which alcoholism occurred. PMID- 4015761 TI - Alcohol abuse in the Old Testament. AB - The Old Testament offers significant lessons in the use and abuse of alcohol and may also contain pertinent clues as to why Jews, rarely abstinent, evince a remarkably low incidence of addictive drinking. Some observations are offered within the context of a modern classificatory system suggested in the Major and Minor Criteria for the Diagnosis of Alcohol outlined in 1972 by the National Council of Alcoholism in the United States. PMID- 4015762 TI - [Peritoneal gliomatosis associated with a mature teratoma of the ovary]. AB - Peritoneal or/and omental implants composed of mature glial tissue is a rare complication of ovarian teratomas. A few cases have been previously reported, and one more case is described. The glial nature of the implants is proved by the presence of glial fibrillary acidic protein. The previous reports of long survival indicate that occurrence of this peritoneal gliomatosis does not alter the prognosis and that therapy directed at the peritoneal implants of mature glia is not required for cure. PMID- 4015763 TI - The effect of heavy maternal alcohol intake on amniotic fluid phospholipids in late pregnancy. AB - The reported effects of alcohol on lung and brain phospholipid metabolism in adult animals have been numerous, but its effect on the fetal lung has not been examined. We investigated the effect of heavy maternal ethanol intake on fetal pulmonary maturation, as measured by the amniotic fluid phospholipids, lecithin and phosphatidylglycerol (PG). Mothers were screened at their first prenatal visit, and detailed drinking histories were taken. Amniotic fluid phospholipids were determined later in pregnancy for clinical purposes, and mothers with positive scores who admitted to drinking during the third trimester were compared to a control group. Amniotic fluid from mothers whose fetuses were exposed to ethanol late in pregnancy did not show the expected increase in lecithin/sphingomyelin and PG related to gestational age that was observed in nondrinking mothers. Canonical correlation of gestational age, late pregnancy drinking, and chronic alcohol problems with amniotic fluid L/S and PG jointly revealed that both gestational age and maternal drinking were significant determinants of fetal lung maturity (r = .39, P less than .05), with active maternal drinking being about one-third as important a determinant as gestational age. These findings could be explained by the known damage-inducing effect of ethanol on alveolar cell membranes or by the effects of ethanol on phospholipid metabolism. PMID- 4015764 TI - Glycohemoglobins in normal and diabetic pregnancy. AB - Glycosylated hemoglobin (HbA1) concentration was measured in 155 pre- and 30 postpartum patients to study its correlation with glucose metabolism and perinatal outcome in patients suspected of carbohydrate intolerance during pregnancy. Though the mean HbA1 values were significantly higher in gestational diabetics compared to normal pregnant controls, the large overlap between HbA1 levels of diabetic patients and levels in the of normal range, make HbA1 an unreliable screening device for diabetes. However, if the HbA1 level was elevated in patients suspected of carbohydrate intolerance, but who had a normal glucose tolerance test, the perinatal outcome in terms of macrosomia and neonatal metabolic abnormalities was similar to that of the group with gestational diabetes. HbA1 measurements should be obtained in these women, and, if elevated, maternal and fetal surveillance is recommended. HbA1 level is not a useful predictor of birthweight, though may be of value as a postpartum screen for unrecognized diabetes and may help discriminate between a constitutionally large but otherwise normal newborn and a large infant of a diabetic mother. PMID- 4015765 TI - Effect of maternal intravenous infusions on fetal extracellular fluid composition in pregnant ewes. AB - Infusion of intravenous solutions to women in labor is common clinical practice. Since these infusions may change the volume and electrolyte balance between the mother and fetus, we investigated the influence of acute maternal volume expansion upon fetal and maternal fluid and electrolyte equilibrium in the chronically catheterized fetal lamb. Paired measurements of maternal and fetal plasma sodium and potassium concentrations, osmolality, and colloid osmotic pressure (COP), plus measurements in the fetal-placental plasma volume were obtained following rapid maternal infusions with saline, dextrose, and dextran solutions. Maternal infusions resulted in changes in fetal electrolyte concentrations as well as alterations in transplacental COP differences. Despite these changes, however, no changes in fetal plasma volume were noted. PMID- 4015766 TI - Successful therapy of unilateral pulmonary emphysema: mechanical ventilation with extremely short inspiratory time. AB - We describe a novel approach to the mechanical ventilation of two neonates with life-threatening unilateral pulmonary emphysema (UPE). Using a standard time cycled, pressure-limited ventilator, we achieved resolution of UPE with shorter inspiratory times than previously reported effective in human newborns (0.10-0.15 sec). We elected this ventilatory strategy in order to direct tidal volume preferentially toward units of lung with relatively normal time constants, while avoiding inflation of longer time-constant emphysematous areas. PMID- 4015767 TI - Progressive chest radiographic changes in wet lung disease. AB - Delayed clearance of fetal lung fluid, or wet lung disease (WLD), is a common, well described clinico-radiographic diagnosis. Unusual chest roentgenographic findings in six infants with WLD are reported. All infants had either delayed development of pleural fluid collections or transient apparent worsening of pulmonary parenchymal infiltrates simulating infection. Five of the six patients were treated with antibiotics. The patients were clinically well, radiographically normal, and culture negative by 72 hours. Our findings suggest that worsening of pulmonary parenchymal opacities and the appearance of pleural effusions can be part of the WLD spectrum. An initial radiographic impression of neonatal pneumonia can be changed to WLD and antibiotics stopped after 72 hours if subsequent radiographs show clearing, cultures are negative, and clinical findings resolve as they did in our patients. PMID- 4015768 TI - Primary management of postpartum vulvovaginal hematomas by angiographic embolization. AB - Three cases of large postpartum vulvovaginal hematomas are reported. After conservative measures including incision and drainage, ligation of bleeding sites, vaginal packing and replacement of volume and coagulation factors failed to control the bleeding in each, pelvic angiography was performed. Brisk arterial bleeding demonstrated on arteriography was controlled by Gelfoam embolization in all three cases. Intra- or postpartum hematologic evaluation revealed a previously undiagnosed coagulation disorder in each patient. The authors suggest that angiography be considered before hypogastric artery ligation whenever possible in patients with large postpartum hematomas and that all such patients be evaluated for coagulopathy. PMID- 4015769 TI - Isoimmunization in pregnancy to Gerbich antigen. AB - A case of hemolytic disease of the newborn due to Gerbich, a public antigen, is presented. The antibody which was IgG1 reacted in vitro with mononuclear phagocytes. Serial sonographic and amniotic fluid examinations were followed and a mildly jaundiced neonate was delivered. Further investigation may establish a relationship between severity of disease and IgG subclasses, a mononuclear phagocyte assay, and sonographic measurements. Sources of compatible blood for possible maternal, fetal, or neonatal transfusion include blood bank rare donor files, relatives, and autologous donation. PMID- 4015770 TI - Nonimmune hydrops fetalis managed with peritoneal dialysis. PMID- 4015771 TI - Prepartum diagnosis of traumatic fetal-maternal hemorrhage. AB - The diagnosis of significant fetal-maternal hemorrhage due to abdominal trauma was made upon detection of fetal red cells in the maternal circulation before delivery, and prompted immediate intervention despite an equivocal fetal monitor tracing. Histologic examination of the placenta identified the area of disruption of the fetal circulation, and the clinical condition of the neonate confirmed the diagnosis. A test for fetal-maternal hemorrhage would be appropriate in the evaluation of any pregnant woman sustaining trauma to the abdomen. PMID- 4015772 TI - Reverse transport of the deceased neonate--an aid to mourning. AB - Parents whose infant has died mourn in a fashion similar to others who experience a significant loss. Seeing and touching the dead infant often facilitate the parents' mourning process. If an infant is transported to another facility for care, and dies while the mother remains hospitalized, the mother may never see her infant again. We have found, in selected cases, that returning the dead infant to its mother at the referring hospital can greatly facilitate parental grieving. Parents who have participated in this aspect of grieving later describe it as a very positive factor in their mourning process. PMID- 4015773 TI - Early childhood developmental follow-up of infants with GMH/IVH: effect of methylxanthine therapy. AB - Theophylline, aminophylline, and caffeine are methylxanthines frequently used in the treatment of idiopathic apnea of prematurity. These agents alter both cerebral blood flow and metabolism and are frequently administered to small preterm neonates, many of whom have experienced germinal matrix and/or intraventricular hemorrhage (GMH/IVH) and thus may suffer underlying disturbances of both cerebral blood flow and metabolism. Our data demonstrate that infants with GMH/IVH required methylxanthine therapy in the neonatal period more often than their nonhemorrhage peers. Because the combined presence of GMH/IVH and methylxanthine therapy may compound the potential for adverse effects in these infants, we analyzed the neurodevelopmental outcome of 73 very-low-birthweight neonates at 18 months corrected age with respect to the presence of GMH/IVH and neonatal methylxanthine therapy. Though further studies are needed, we cautiously conclude that the 18-month Bayley mental score demonstrates no harmful effects of neonatal methylxanthine therapy on cognitive functioning. PMID- 4015774 TI - Do computers help or hinder the clinical evaluation of alternative treatments in perinatal medicine? PMID- 4015775 TI - Maximizing the efficiency of a study on alcohol-related birth defects by means of data collection and analytic strategy dissociation. AB - Application of the terms "prospective" and "retrospective" to quasi/experimental research designs used in clinical investigations is often ambiguous; they often lack specification as to whether they apply to data acquisition, analytic strategy, or both. Data may be collected prospectively by preplanned protocol or retrospectively by chart review. In addition, the direction of analysis may be prospective--comparing differential outcomes for at-risk and not at-risk (exposed/not exposed) groups--or retrospective--comparing differential preceding risks for affected and nonaffected groups. Prospective data collection is advantageous in assuring the availability of crucial variables for an entire sample, but prospective analytic strategies may be inefficient, underestimating effect sizes, particularly when the outcome of interest is rare or the effect, even if large, is seen in only a small proportion of cases. In a prospective multilinear regression model of risks for lowered birthweight for gestational age, 2% of the variance was explained by alcohol variables after adjustment for confounding. In comparison, a similar multilinear regression of case-control sample, in which the frequency of the abnormal outcome is raised, showed 18% of the variance explained by alcohol variables. Data collection and analytic strategies may be dissociated. Although some statistical power may be lost because of reduced sample size, synthetic case-control analysis is efficient in examining small effects. It also has the advantage of decreasing the size of the database to be managed and the time required for analysis. Using this approach, it is feasible to perform virtually any analysis that can be done on a mainframe on medium-sized departmental computer system. PMID- 4015776 TI - The importance of epidemiological studies of allergy in Asia and the Pacific. PMID- 4015777 TI - Acquired immune deficiency syndrome in Thailand. PMID- 4015778 TI - Abstracts of the papers presented at the annual meeting of the Allergy and Immunology Society of Thailand. Bangkok, 22nd March 1985. PMID- 4015779 TI - Live attenuated varicella vaccination in immunocompromised children. PMID- 4015780 TI - Intracutaneous tests, radioallergosorbent tests, total serum IgE determinations, total eosinophil counts and nasal eosinophilia in the diagnosis of allergic diseases. PMID- 4015781 TI - Alterations of immune profile among villagers in Flores, Indonesia. PMID- 4015782 TI - Clinical significance of the Lewis red blood cell system to transfusion practice in Thailand. PMID- 4015783 TI - Rye grass allergen induced lymphocyte proliferation. PMID- 4015784 TI - Is blending the graminean allergens a reliable practice? An evaluation of blending graminean allergens. PMID- 4015785 TI - Aerosol therapy of bronchial asthma. PMID- 4015786 TI - Aggression and violence. PMID- 4015787 TI - The use of standardized assessment procedures in the evaluation of patients with multiple injuries. AB - The accuracy of diagnosis in multiple trauma can be greatly improved by the use of standardized assessment routines and standard documentation. In the two groups of patients reviewed the diagnostic error rate fell from 23% in the period 1979 1980 to 8% for the period 1981-1982. PMID- 4015788 TI - Air weapon injuries in children: a case for education. AB - The results of the first 6 months of a 2-year prospective study on the frequency, severity and methods of prevention of air weapon injuries to children are reported. Twenty-eight cases presenting to an urban paediatric accident and emergency department have been analysed. Nineteen of these were males between the ages of 10 and 16 years. At least 18 incidents occurred in public places. The five most serious injuries were of the orbit, face and abdomen. Another nine injuries were near vital structures. Education is needed on the existing guidelines for the safe use of air weapons. PMID- 4015789 TI - Air rifle ammunition and its influence on wounding potential. AB - Two new types of air rifle pellet have been introduced; Prometheus, made from steel and nylon, and 'Sabo', made from lead alloy and plastic. Both have radio opaque and radio-lucent components and their manufacturers claim better penetration. To establish their capabilities and the clinical implications a comparison of penetration was made between diablo, Prometheus and 'Sabo' pellets using gelatin 20% as a tissue simulant. Prometheus penetrated no further than diablo pellets but fragmented in up to 70% of cases. 'Sabo' penetrated 46% further than diablo (p = 0.001) and its plastic component did not penetrate at ranges greater than 0.5 m. Prometheus penetrated steel, unlike the other pellets, and is therefore potentially more dangerous in head injury. Because of fragmentation after impact it should be remembered that the radio-lucent sleeve is likely to be lying in the wound track. 'Sabo' would appear to be the most dangerous in soft and medium density materials. PMID- 4015790 TI - Wound healing. AB - The majority of wounds encountered in the accident and emergency department are superficial in nature and a consequence of accidental trauma or the elective surgical incision of infected foci. The techniques of management of such cases have undergone few changes in recent years, and any advances of a practical or therapeutic nature have been comparatively modest. On the other hand, many major advances have occurred in our understanding of the factors involved in the basic pathophysiology of wound repair. This paper is a summary of our present concept of the process of repair in soft tissues. PMID- 4015791 TI - A study of stab wounds. AB - A study was made of patients with stab wounds who attended the Accident and Emergency Department of Glasgow Royal Infirmary during 1978 and 1983. There were 318 patients. The majority, 304 (96%), were males. A total of 87 (27%) were teenagers. The most common sites of the wounds were the chest (143 patients) and the abdomen (113 patients). The features of the patients and their wounds are compared with those of a previous study carried out at the same hospital in the early 1960s (Batey & MacBain, 1967). The post-mortem reports of 25 fatal stab injury cases occurring in Glasgow between 1971 and 1978 are also reviewed. Some aspects of diagnosis, management and prevention of stab wounds are discussed. PMID- 4015792 TI - Simultaneous traumatic rupture of the quadriceps tendons. AB - A case is reported of simultaneous traumatic rupture of quadriceps tendons diagnosed in the accident and emergency department within 2 hours of injury. This is an extremely rare injury and diagnosis is often missed. Possible mechanism of the injury, predisposing factors, guidelines for diagnosis and results of surgical treatment are discussed, and the literature is reviewed. PMID- 4015793 TI - Do accident and emergency patients collect their prescribed medication? AB - One month's prescriptions from an accident and emergency department were examined. Of these 16% were found not to have been dispensed by the chemist. The commonest drugs prescribed were antibiotics (60%) and analgesics (22%). Most age groups were guilty of failing to collect drugs--primary non-compliance. PMID- 4015795 TI - AIDS and the accident and emergency department. PMID- 4015794 TI - Plasma catecholamine concentrations in acute states of stress and trauma. PMID- 4015796 TI - Dislocation of the distal radio-ulnar joint. PMID- 4015797 TI - Re: Myocardial infarction and ventricular rupture. PMID- 4015798 TI - The Lixiscope portable imaging device: an assessment of its use in the accident and emergency department. PMID- 4015799 TI - An indication for human tetanus immunoglobulin in unimmunized patients. PMID- 4015800 TI - Intravenous drug abuse and the accident and emergency department. AB - A 4-month prospective study of intravenous drug abusers attending an accident and emergency department was performed. A total of 92 patients presented with 104 new complaints. Seventy-eight per cent of patients were under 30 years of age and 28% were female. The primary reason for attendance was related to trauma in 30% of attendances, accidental or deliberate overdose in 26% and as a result of infection in 26%. A total of 37% of all attendances resulted in admission and two patients died in the department. Fifty-four patients (58%) had radioimmunoassay performed for hepatitis B markers and there was evidence of past or ongoing infection in 87% of these patients. Only three patients (5.6%) were HBsAg positive at the time of presentation. Accident and emergency staff should be made aware of the pattern of attendance of intravenous drug abusers and the particular problems they present. PMID- 4015801 TI - Neuromuscular paralysis caused by an overdose of emepronium bromide (Cetiprin). AB - Emepronium bromide (Cetiprin) is an anticholinergic agent used therapeutically to reduce urinary frequency. We describe a voluntary overdose, which caused respiratory failure due to neuromuscular paralysis. PMID- 4015802 TI - The vagrant in the accident and emergency department. AB - Those of no fixed abode constituted only 0.3% of all new patients seen in one year. The majority presented with a disorder due to acute medical illness or trauma. This group has poor access to general practitioners, and turns to the accident and emergency department for medical care. However, the number of investigations performed and the number admitted to hospital indicate a substantial amount of serious pathology. The proportion of homeless attenders abusing the accident and emergency facilities is small. PMID- 4015803 TI - Head protection for horse riders: a cause for concern. AB - We report the frequency with which horse riders with a significant head injury present to a large accident and emergency department. We have also recorded details about the use of headwear and conclude that horse-riding is associated with a serious risk of head injury and 'protective' headwear may not always protect. PMID- 4015804 TI - The London marathon: 3 years in the running. AB - Over the 3 years from 1982 to 1984, a total of 34 patients were seen in the Accident and Emergency Department of St Thomas' Hospital, London, as a result of the London Marathon. Clinical details are discussed. Considering the number of annual runners who take part, the casualties from the finish of this event are low. This short report suggests that the 3 years' preparation and organization for the finish of the London Marathon were consistently effective. PMID- 4015805 TI - Bronchogenic carcinoma presenting as an injured thumb. AB - A case of bronchogenic carcinoma presenting as a hand injury is described. The difficulties in diagnosis are highlighted. The importance of radiology is demonstrated. Palliative surgery is recommended for pain relief. PMID- 4015806 TI - Rotational panoramic zonography. PMID- 4015807 TI - [Ethical aspects in the publishing of medical periodicals]. PMID- 4015808 TI - [Values for red blood cells, leukocytes and platelets during the first 8 weeks of life at an altitude of 2,650 meters]. PMID- 4015809 TI - [Epidemiology of bacteremias in a neonatal intensive care unit]. PMID- 4015810 TI - [Comparative study of 1-deamino-8-D-arginine vasopressin, hydrochlorothiazide and chlorpropamide in the treatment of central diabetes insipidus]. PMID- 4015811 TI - [Postsurgical bleeding caused by carbenicillin]. PMID- 4015812 TI - [Transient hyperphosphatasemia in infants]. PMID- 4015813 TI - [Hernia of Grynfeltt's triangle. Presentation of 2 cases]. PMID- 4015814 TI - [Chronic peritoneal dialysis and social rehabilitation of uremic children in the Third World]. PMID- 4015815 TI - [Reye's syndrome and the administration of acetylsalicylic acid in children]. PMID- 4015816 TI - [Use of the muscle biopsy in the diagnosis of Reye's syndrome]. PMID- 4015817 TI - [Persistent ductus arteriosus; classification and study of 24 cases]. PMID- 4015818 TI - [Prognosis of the child with epilepsy. Follow-up of 398 cases]. PMID- 4015819 TI - [Normal dimensions determined by ultrasound for the gallbladder and the suprahepatic, splenic, inferior cava and portal veins in the child]. PMID- 4015820 TI - [Traumatic hernia of the diaphragm in children]. PMID- 4015821 TI - [Pseudoaneurysm of the abdominal aorta secondary to umbilical artery catheterization]. PMID- 4015822 TI - [Maternal nutrition and the growth of the nursing infant]. PMID- 4015823 TI - Molecular abnormality and cDNA cloning of human aldehyde dehydrogenases. AB - Usual human livers contain two major ALDH isozymes, i.e., cytosolic ALDH1 and mitochondrial ALDH2, while approximately 50% of Orientals are "atypical" and have only the ALDH1 and are missing the ALDH2. Instead, the atypical livers contain an enzymatically inactive but immunologically cross-reactive material (CRM) corresponding to the ALDH2 component. Some Orientals are found to be atypical also in the ALDH1 locus, i.e., they are missing the enzymatically active ALDH1 but contain a large amount of CRM corresponding to the ALDH1 component. cDNA for ALDH1 and that for ALDH2 were cloned and their nucleotide sequences were determined. The amino acid sequences of ALDH1 and ALDH2 were deduced from their cDNA sequences. The molecular abnormality of the inactive ALDH2(2) is found to be the substitution of Glu at the 14th position from the COOH-terminal of the protein by Lys which resulted from G----A transition in the gene. PMID- 4015824 TI - Subcellular distribution of aldehyde dehydrogenase activities in human liver. AB - The subcellular distributions of aldehyde dehydrogenase activities towards acetaldehyde have been determined in wedge-biopsy samples of human liver. A form with Km values of less than 1 microM and 285 microM towards acetaldehyde and NAD+ respectively was present in the mitochondrial fraction. This enzyme had no detectable activity towards N-tele-methylimidazole acetaldehyde, the aldehyde derived from the oxidation of N-tele-methylhistamine. The activity in the cytosol was more sensitive to inhibition by disulfiram and had Km values of 270 microM and 25 microM for acetaldehyde and NAD+, respectively. It was active towards N tele-methylimidazole acetaldehyde with a Km value of 2.5 microM and a maximum velocity that was 40% of that determined with acetaldehyde. Both these cytosolic activities had alkaline pH optima. PMID- 4015825 TI - Use of cyanamide to determine localization of acetaldehyde metabolism in rat liver. AB - Various techniques have been employed previously to show that acetaldehyde is primarily oxidized in the mitochondrial matrix of rat liver. In this study, a new approach was tested. Mitochondrial low-Km aldehyde dehydrogenase (ALDH) was partially inactivated and the effect on acetaldehyde oxidation measured. Cyanamide was chosen as the ALDH inhibitor. An enzymatic activation of cyanamide, probably by catalase, was necessary for the drug to inhibit ALDH activity. The level of remaining ALDH activity after cyanamide treatment was correlated with the ability of either rat liver mitochondria or liver slices to oxidize acetaldehyde. Any inhibition of ALDH resulted in a decreased rate of acetaldehyde oxidation, indicating that there is no excess of ALDH in the cell above what is needed to oxidize acetaldehyde. Approximately 15% of the acetaldehyde disappearance at 200 microM was catalyzed by high-Km ALDH, and nearly 30% of the acetaldehyde was lost through binding to cytosolic proteins. PMID- 4015826 TI - Structure vs. activity in the sulfonylurea-mediated disulfiram-ethanol reaction. AB - The oral hypoglycemic agents, chlorpropamide (CP) and tolbutamide (TB) are known to elicit a clinical disulfiram-ethanol reaction (DER) when consumed with alcohol. In rats, this DER is manifested in vivo by the elevation of blood acetaldehyde (AcH) levels, a consequence of the inhibition of hepatic aldehyde dehydrogenase (AIDH). Administration of CP or TB to rats (1.0 mmol/kg, IP), followed by ethanol one hour before sacrifice, raised blood AcH levels 12- and 2 times that of control animals, respectively for CP and TB when measured at 3 hours, and 20-fold and 8-fold at 16 hours post drug administration. CP and TB had no effect on AIDH activity when incubated with either intact or osmotically disrupted rat liver mitochondria, indicating that a metabolite of CP or TB is responsible for the inhibition of AIDH in vivo. Hydrolysis products of CP, the 2' hydroxylated products of CP, tolpropamide and tolethamide, or the 3'-hydroxylated analogs of CP and tolpropamide, were uniformly inactive in elevating ethanol derived blood AcH. Pretreatment of rats with 3-amino-1,2,4-triazole or SKF-525A had no effect on the elevation of blood AcH mediated by CP or TB, while phenobarbital pretreatment decreased blood AcH by 69%. Although our results clearly indicated that side chain hydroxylation and subsequent oxidation do not play a role in AIDH inhibition by CP or TB, the nature of the side chain attached to the sulfonylurea moiety appears to influence this inhibitory activity in vivo. Thus, the order of activity in the homologous series was, chlorpropamide greater than chlorbutamide greater than chlorethamide much greater than chlormethamide, chlorisopropamide = 0. PMID- 4015827 TI - Differential effects of ethanol on two synaptic membrane Ca2+ transport systems. AB - The Na+-Ca2+ exchange activity in synaptic plasma membranes is inhibited by very low concentrations of ethanol (less than 25 mM). The high affinity Mg2+- and ATP dependent Ca2+ transport in highly purified synaptic membranes is much less sensitive to inhibition by ethanol, with no statistically significant inhibition observed until an ethanol concentration of nearly 800 mM was used. Manipulations of the lipid environment designed to increase membrane fluidity enhanced the activity of the Na+-Ca2+ exchange system but inhibited the ATP-dependent Ca2+ pump. The differential responses of the two synaptic plasma membrane Ca2+ transporting systems to such modifications of membrane structure suggest that these two ion transport processes differ in the extent to which their activity is dependent on the lipid microenvironment in which they reside. Thus, the effects of ethanol on the Na+-Ca2+ antiporter may represent a fairly selective inhibitory process. PMID- 4015828 TI - Alterations in Ca2+-dependent and Ca2+-independent release of catecholamines in preparations of rat brain produced by ethanol treatment in vivo. AB - Compared to preparations from control animals, superfused striatal slice preparations from brains of rats treated chronically with ethanol released a significantly greater fraction of stored [3H] dopamine on depolarisation in 40 mM K+. Similarly, the electrically-evoked release of [3H]-norepinephrine from cortical slices and of [3H]-dopamine from striatal slices is also increased, although with this mechanism of depolarisation the change is significant only in the case of [3H] norepinephrine release. In contrast to this tendency to enhancement of Ca2+-dependent depolarisation-induced release, a reduced fraction of stored [3H]-catecholamines was released from these preparations by the indirect sympathomimetics tyramine and (+)-amphetamine. The catecholamine release induced by these indirect sympathomimetics is largely independent of external Ca2+ and the results are interpreted as suggesting that chronic alcohol treatment changes the distribution of catecholamine neurotransmitters between storage pools in the nerve terminal which do or do not require Ca2+ entry for release. PMID- 4015829 TI - Alcohol and the calcium-dependent potassium transport of human erythrocytes. AB - In vitro exposure of human red blood cells to ethanol (100 and 400 mM) was found to increase the initial rate of calcium-dependent potassium efflux through the red cell membrane. This effect of ethanol was apparently not due to an elevation of the intracellular free calcium but rather to a direct action of the drug on the transport process as, (1) intracellular calcium concentrations were tightly buffered with EGTA, (2) ethanol did not alter the efflux of 45Ca from the cells, and (3) dantrolene, which has been proposed to counteract the effect of ethanol on intracellular calcium levels in the erythrocyte, did not inhibit the stimulatory action of ethanol. The efflux of potassium from erythrocytes obtained from chronic alcoholics was not different from that of erythrocytes from non alcoholic individuals. The relationship of these findings to neuronal potassium transport is discussed. PMID- 4015830 TI - The effect of ethanol and calcium on fluid state of plasma membranes of rat hepatocytes. AB - Basolateral (blLPM) and canalicular (cLPM) plasma membrane vesicles were isolated from rat liver to compare membrane fluidity, fluidity responses to membrane perturbants, and the relationship between fluidity and a membrane protein function such as carrier-mediated taurocholate transport. Membrane fluidity was measured by fluorescence polarization using 1,6-diphenyl-1,3,5-hexatriene as a probe. Uptake of [3H] taurocholate was measured by a rapid Millipore filtration technique. blLPM were more fluid than cLPM. Ethanol produced a concentration dependent fluidizing effect on both membrane preparations, the change being greater in blLPM. Incubation with calcium for 2 hr at 37 degrees C rendered both membrane preparations more rigid, again the cLPM being more resistant to perturbation. There was a linear correlation between an increase in membrane fluidity and inhibition of taurocholate uptake into blLPM in the presence of increasing concentrations of ethanol. The data support the concept that membrane lipid fluidity is an important regulator of membrane protein functions and hence also of overall cellular activity. PMID- 4015831 TI - Effect of ethanol on fatty acid metabolism in cultured hepatocytes: dependency on incubation time and fatty acid concentration. AB - In a previous report it was shown that ethanol increases the rate of accumulation of triacylglycerol by 90% in hepatocytes in primary culture. This represents the first known suitable model for in vitro studies of the ethanol-induced fatty liver. The biochemical alterations causing this accumulation of triacylglycerol remain to be elucidated, however. In the present report it is shown that (1) the effect of ethanol exhibits a time lag of 6-9 hours (2) the increment in the content of triacylglycerol caused by ethanol is increased by increased concentrations of fatty acids (3) the fatty acid uptake is not affected by ethanol (4) fatty acid synthesis is inhibited 20% by ethanol (5) the contents of diacylglycerol and phospholipids are not affected by ethanol (6) addition of ethanol increases the cytosolic and mitochondrial redox levels. It is concluded that ethanol is likely to exert its effect on the accumulation of triacylglycerol by redistributing fatty acids between oxidation and triacylglycerol synthesis and/or between storage and secretion of triacylglycerol. PMID- 4015832 TI - Effects of chronic ethanol consumption on male Syrian hamster hepatic, microsomal mixed-function oxidases. AB - Chronic alcohol consumption significantly increases the risk of drug interactions. We have described its effects on hamster microsomal monooxygenases. Male Syrian hamsters (85 g) were given 10% ethanol in water and food ad lib for up to 6 weeks. Microsomal electron transport components and metabolism of ethylmorphine, benzphetamine, aniline, and acetaminophen were measured. At 4 weeks, SDS-PAGE of ethanol microsomes showed an induced band with an Mr of 53,900 daltons and there was a 2-3 fold stimulation of aniline and acetaminophen metabolism. Cytochrome P-450 increase was not significant. For the six week period, Caloric intake (3 weeks, p less than 0.001), liquid consumption (3 weeks, p less than 0.05) and body weights (6 weeks, p less than 0.05) of ethanol animals were significantly greater than controls; kidney weights were significantly less (p less than 0.05). Ethanol consumption increased from 20% of the daily caloric intake (week 1) to 31% (week 6). Induction of specific substrate metabolism without apparent deleterious physiological changes establishes hamsters fed 10% ethanol in drinking water as a biochemical model for the study of chronic alcohol consumption and specific drug interactions. PMID- 4015833 TI - Comparative effects of short chain alcohols on lipid phase transitions. AB - We have been systematically investigating the physical interactions of alcohols with synthetic lipids in order to elucidate the mechanisms of alcohol intoxication. It has previously been shown that the effects of ethanol on the phase transition temperatures of saturated chain phosphatidylcholines (PC's) are biphasic [11]. The secondary high concentration effect has recently been shown to be due to a transition to a new completely interdigitated state [16]. In the present report we have investigated the influence of the chain length of the alcohol on the induction of this interdigitated state. We demonstrate that all three alcohols have a biphasic effect on the transition temperature of PC, and the comparison of the concentration dependencies of this effect for the three alcohols provides some insight into the possible mechanism of the transition. The potential biological importance of this secondary alcohol-membrane interaction is discussed. PMID- 4015835 TI - Role of alcohol P-450-oxygenase (APO) in microsomal ethanol oxidation. AB - The form of liver microsomal cytochrome P-450 induced by chronic administration of ethanol to rabbits, designated as P-450ALC or P-450 isozyme 3a, has been purified to homogeneity as judged by several criteria, including NH2- and COOH terminal amino acid sequence determination. The reconstituted alcohol-P-450 oxygenase (APO) system containing P-450ALC and NADPH-cytochrome P-450 reductase catalyzes the oxidation of a variety of primary and secondary alcohols to aldehydes and ketones, including methanol, ethanol, n-propanol, n-butanol, 2 butanol, n-pentanol, and cyclohexanol. Other purified P-450 cytochromes, including isozymes 2, 3b, 3c, 4, and 6, are much less active than P-450ALC in the oxidation of alcohols. That P-450ALC functions in ethanol oxidation in liver microsomal membranes as well as in the reconstituted system was shown by immunochemical experiments involving inhibition by sheep anti-P-450ALC antibodies. We conclude that P-450ALC is the predominant ethanol-oxidizing cytochrome present after induction by chronic alcohol administration and that the other P-450 cytochromes have low but significant activity in both control and ethanol-induced animals. PMID- 4015834 TI - Phosphatidylinositol composition in pancreas and submaxillary gland of ethanol fed rats. AB - The possibility that changes in the stimulus-secretion coupling are involved in the etiology of pancreatitis was investigated by analysis of the molecular composition of the phosphatidylinositols in pancreas of rats fed a liquid ethanol containing diet and pair-fed controls. The arachidonoyl-containing phosphatidylinositols were about half as abundant in the ethanol-fed rats. Opposite differences were seen for the major species containing linoleoyl, oleoyl or stearoyl groups at C-2. Ethanol-induced lipid peroxidation did not seem to be involved, since carbon tetrachloride administration had no effect on the composition. In the submaxillary gland, that has a similar stimulus-secretion coupling, the arachidonoyl-containing phosphatidylinositols constituted about a 25% smaller fraction in the ethanol-fed rats. Dexamethasone administration did not change the effect. Possibly, decreased secretory response in these glands in ethanol-fed rats is caused by the change in phosphatidylinositol composition. PMID- 4015836 TI - Effect of ethanol on the microsomal glutathione S-transferase activity in glutathione-depleted rat liver. AB - Depletion of hepatic glutathione in male rats by starvation caused a significant increase in microsomal glutathione S-transferase activity, which was not affected by acute ethanol pretreatment. An additional depletion in fasted rats by diethylmaleate (0.5 g/kg) caused a further increase in the enzyme activity, but this increase was delayed in ethanol intoxicated rats. Although ethanol caused a small increase in hepatic microsomal lipid peroxidation in control animals, this effect of ethanol was not observed in diethylmaleate treated rats and thus was apparently not responsible for the delay in enzyme activation. It is suggested that the activation of microsomal glutathione S-transferase activity towards 1 chloro-2,4-dinitrobenzene in glutathione-depleted rat liver may be produced by changes in thiol/disulfid ratio and/or some reactive oxygen species. PMID- 4015837 TI - Hepatic catalase and superoxide dismutases after acute ethanol administration in rats. AB - The administration of an acute ethanol load (2.3 g/kg, IP) to rats is followed by a decrease of the hepatic activity of cytosolic catalase, a decrease which precedes a reduction in the cytosolic Cu, Zn-superoxide dismutase (SOD) activity. Desferrioxamine, an iron chelator and scavenger of superoxide radicals, administered prior to ethanol, prevents the changes in the cytosolic catalase activity, changes which are unaffected by the administration of allopurinol, an inhibitor of xanthine oxidase. These data favour the hypothesis that acute ethanol results in an overproduction of oxygen free radicals which affects primarily the cytosolic catalase activity and increases hereby susceptibility of Cu, Zn-SOD to these radicals. They suggest also that xanthine oxidase does not play a major role in oxygen radical production in the liver cytosol during acute alcohol intoxication. PMID- 4015838 TI - Some unexplained features of hepatic ethanol oxidation. AB - Ethanol is an excellent substrate for the liver, competing effectively for oxidation with other substrates such as fatty acids. Using isolated liver cells from fed and starved rats, we have found that ethanol strongly inhibits Krebs cycle oxidations, so that the combustion through the cycle of acetyl CoA, derived from fatty acids, is reduced more than 50%. In contrast, fatty acid beta oxidation to acetyl CoA is inhibited only 20% in fed and fasted states. Ethanol was not antiketogenic. In the fed state, octanoate but not palmitate inhibited ethanol oxidation whereas in cells from fasted rats palmitate inhibited ethanol oxidation. Gluconeogenesis from lactate was reduced 50% in hepatocytes from fasted rats but oxygen consumption was unaffected. This paradoxical maintenance of oxygen consumption in a state where the only overt need for ATP synthesis is depressed, suggests that ethanol oxidation may not be exclusively coupled to ATP synthesis but also can be linked to other energy transducing processes. PMID- 4015839 TI - Biochemical and genetic studies on mouse aldehyde dehydrogenases. AB - Aldehyde dehydrogenase (AHD) exists as isozymes which are differentially distributed among tissues and subcellular fractions of mouse tissues. Genetic variants for liver mitochondrial (AHD-1) and cytoplasmic (AHD-2) isozymes have been used to map the responsible loci (Ahd-1 and Ahd-2) on chromosomes 4 and 19 respectively. Evidence for a regulatory locus (Ahd-3r) controlling the inducibility of the mouse liver microsomal isozyme (AHD-3) has also been obtained. More recent studies have described genetic and biochemical evidence for three additional AHD isozymes: a stomach isozyme (AHD-4); another liver mitochondrial enzyme (AHD-5); and a testis isozyme (AHD-6). Genetic analyses have indicated that AHD-4 and AHD-6 are encoded by distinct but closely linked loci on the mouse genome (Ahd-4 and Ahd-6), which segregate independently of Ahd-1 and Ahd-2. Liver mitochondrial isozymes, AHD-1 and AHD-5, have been purified to homogeneity using affinity chromatography. The very high affinity of AHD-5 for acetaldehyde suggests that this enzyme is predominantly responsible for acetaldehyde oxidation in mouse liver mitochondria. PMID- 4015840 TI - Biochemical genetic analysis of human and rodent aldehyde dehydrogenase (ALDH). AB - ALDH isozymes have been characterized in terms of substrate and coenzyme specificity, heat stability, tissue distribution and electrophoretic properties. The activity of the isozymes has also been examined in rodent-human somatic cell hybrids in order to map the structural genes to specific chromosomes and to study the control of gene expression. One isozyme, designated ALDH3, which is very active against benzaldehyde, was found to show variable expression in hybrids made between rat hepatoma cells and human fibroblasts or fetal liver. Segregation analysis of these hybrids indicates that the structural locus for human ALDH3 may be on chromosome 17. The expression of rodent ALDH3 in these hybrids was extremely variable and not correlated with the appearance of the human enzyme. In hybrids expressing human and rodent ALDH3 no heteromeric isozymes were observed. The human "cytosolic" ALDH1 and "mitochondrial" ALDH2 isozymes did not appear to be expressed in any of the somatic cell hybrids examined. PMID- 4015841 TI - Ethanol feeding can produce secondary alterations in aldehyde dehydrogenase isozymes. AB - Depressed hepatic aldehyde dehydrogenase (ALDH) activity levels have been observed in alcoholics, but whether the deficit is primary or secondary in nature remains controversial. In this study, we examined liver ALDH in rodent (rat) and primate (baboon) animal models pair-fed nutritionally adequate ethanol or isocaloric carbohydrate containing liquid diets. Both species show qualitative changes in ALDH isozymes after ethanol consumption. The changes include alterations in isozyme patterns seen upon electrofocusing and decreased responsiveness to the ALDH inhibitor, disulfiram. The subcellular locus of most of the changes is cytosolic in the baboon and mitochondrial in the rat. Study of partially purified (enriched) baboon cytosolic ALDH confirmed changes seen in the original cytosols and kinetic characterization of the enriched enzyme revealed a 9-fold higher Km for acetaldehyde in ALDH from an ethanol treated animal. We note that qualitative and quantitative changes secondary to ethanol treatment in the primate model closely parallel those described in human alcoholics. PMID- 4015842 TI - Modification of thiol groups in cytoplasmic aldehyde dehydrogenase. AB - It is proposed that cytoplasmic aldehyde dehydrogenase possesses a pair of important reactive thiol groups, A and B. Group A is labelled by disulfiram and the enzyme is inactivated; subsequently group B displaces the dithiocarbamate label and an enzymic disulphide is formed. On the other hand, it appears that group B is labelled by 2,2'-dithiodipyridine resulting in activation of the enzyme. Again, the label (2-thiopyridone) is later displaced, this time presumably by group A, giving rise to loss of enzymic activity and formation of the same disulphide species as is produced by disulfiram. Methyl diethylthiocarbamyl disulphide and methyl 2-pyridyl disulphide supply the same label (MeS-) but the first compound inactivates the enzyme while the second activates it. It is concluded that the first of these reagents modifies group A and the second group B. It appears that methyl 4-pyridyl disulphide may react non specifically with both groups A and B. Group A is a possible candidate for a catalytically essential nucleophile in the actions of aldehyde dehydrogenase. PMID- 4015843 TI - A drug discrimination analysis of ethanol-induced behavioral excitation and sedation: the role of endogenous opiate pathways. AB - The drug discrimination technique was used to characterize the biphasic behavioral effects of ethanol (ETOH) and examine the role of opiate pathways in mediating ETOH's excitatory (EX) and sedative (SED) phase effects. Forty Sprague Dawley rats were trained to perform ETOH vs. saline discriminations during either ETOH's EX (6 min post-dose) or SED (30 min post-dose) phase of action in a double lever food reinforced operant paradigm. After animals had achieved the required performance criterion, dose-response and phase-generalization tests were conducted in each group. In addition, preliminary studies were conducted to examine the effect of naloxone (NLX) pretreatment on discrimination of ETOH's EX and SED phase stimulus effects. Results of generalization testing demonstrate that discrimination of ETOH was dose-dependent and there was no generalization between phases regardless of the initial training condition. NLX pretreatment significantly attenuated discrimination of ETOH's EX phase effects but was ineffective in antagonizing ETOH's SED effects. These data demonstrate that the stimulus properties of ETOH are phase-dependent and suggest that opiate pathways are critical for the expression of ETOH's EX phase behavioral effects. PMID- 4015844 TI - Cross-tolerance between ethanol and chlordiazepoxide. AB - Drug-induced hypothermia was used to investigate drug tolerance and cross tolerance. C57BL/6J mice, which were injected with a single dose of chlordiazepoxide (CDP; 30 mg/kg) one day before and reinjected with an equivalent dose of CDP the next day, did not develop tolerance to the drug. However, ethanol pretreated (3.5 g/kg, 24 hr earlier) mice, when injected with CDP (30 mg/kg), showed cross-tolerance to CDP. The cross-tolerance was short-lived (less than 48 hr). On the other hand, CDP-pretreated mice (30 mg/kg, 24 hr earlier) did not show cross-tolerance to ethanol. The lack of a reciprocating effect of CDP pretreatment was not likely to be due to the difference in initial dosage between ethanol and CDP. It may be due to different rates of tolerance development or different mechanisms of actions between CDP and ethanol. Mice chronically treated with ethanol also showed a similar degree of cross-tolerance to CDP compared to those exposed to an acute dose of ethanol. PMID- 4015845 TI - Perforant pathway lamination in the dentate gyrus is unaffected by prenatal ethanol exposure. AB - The entorhinal (perforant path) projection to the dentate gyrus was labeled with an anterograde horseradish peroxidase method to test whether prenatal exposure to ethanol affected the normal development of afferent lamination. Mean ethanol consumption of the ethanol-consuming dams was 12.7 g/kg +/- 0.3 g per day during days 1-21 of gestation. Adult offspring of normal and pair-fed controls as well as ethanol-exposed rats were analyzed. Computer-assisted image analysis of the entorhinal terminal field organization revealed no permanent changes in the development of the afferent lamination pattern in the dentate gyrus molecular layer in spite of the heavy in utero ethanol exposure. PMID- 4015846 TI - Basal firing rate of rat locus coeruleus neurons affects sensitivity to ethanol. AB - Intracellular recordings were made from spontaneously active rat locus coeruleus (LC) neurons in a totally submerged brain slice preparation. Bath application of ethanol (ETOH) (1-60 mM) inhibited the spontaneous firing of LC neurons. These ETOH concentrations are equal to or below ETOH concentrations found in the brain during mild to moderate intoxication. The basal frequency of spontaneous firing of LC neurons ranged from 0.4-7 Hz. For 9 LC neurons which showed complete block of firing by ETOH, the latency to block was found to be directly related to the logarithm of the firing rate (correlation coefficient 0.94). This relationship was not secondary to a relationship between membrane potential and latency to block since for the same 9 neurons, membrane potential and latency to block were not significantly correlated. We conclude that the basal firing rate of a neuron can affect its sensitivity to the inhibitory effects of ETOH. PMID- 4015847 TI - Ethanol increases rat liver tryptophan oxygenase: evidence for corticosterone mediation. AB - Acute administration of ethanol (4.0 g/kg) intragastrically or intraperitoneally induced rat liver tryptophan oxygenase (TO) activity 3-4 fold 4-5 hr later. Ethanol administration increased the concentration of plasma free tryptophan and free fatty acids. Pretreatment with a beta-receptor blocker, propranolol, modified the latter responses without affecting the TO induction due to ethanol. The rise of the level of plasma free tryptophan due to ethanol was too small to influence TO activity. Liver tryptophan concentration and TO half-life was unchanged after ethanol administration. Ethanol administration increased the concentration of plasma corticosterone sufficiently to increase TO activity. Pretreatment with a glucocorticoid antagonist blocked this TO response to ethanol. The increased TO activities found after ethanol or corticosterone treatment were influenced in the same manner and to the same extent by cycloheximide. Taken together it is concluded that ethanol induces TO through a rise of glucocorticoid hormones and not by a tryptophan-linked mechanism. PMID- 4015848 TI - Temperature modulates ethanol sensitivity in mice: generality across strain and sex. AB - Findings in our laboratory indicate that body temperature alters ethanol potency as measured by sleep-time, wake-up brain ethanol concentration and mortality in male C57BL/6J mice. The current studies tested the generality of these results. Experiment one tested age-matched, drug-naive, male C57BL/6S and BALB/cS mice. Experiment two tested age-matched, drug-naive, male and female C57BL/6J mice. Each mouse was injected IP with 3.6 g/kg ethanol (20% w/v). After losing its righting reflex, the mouse was placed into a v-shaped sleep tray within a chamber kept at a designated temperature from 12 to 36 degrees C. Upon awakening, rectal temperature was measured and blood and brain samples were taken for gas chromatographic analysis. As in previous studies, ambient temperature modulated the body temperatures and sleep-times of intoxicated animals. More important, wake-up rectal temperatures were positively correlated with sleep-times and negatively correlated with wake-up ethanol concentrations in all animals tested. These results support the hypothesis that brain sensitivity to ethanol depression varies with body temperature in accordance with membrane perturbation theories of anesthesia. PMID- 4015850 TI - Dynamic aspects on acute tolerance to hexobarbital evaluated with an anesthesia threshold. AB - Induction of acute tolerance was studied with hexobarbital in male rats. A threshold technique utilizing an EEG-criterion consisting of a burst suppression of 1 second or more (the SS) was used both to induce and maintain anesthesia. Hexobarbital was infused with an optimal dose rate of 15 mg/kg/min. The infusion was stopped at the criterion and restarted when no SS had been seen for 1 min. The doses of hexobarbital needed to maintain anesthesia were fairly constant around 3.5 mg/kg/min up to durations of 120 min which indicates that redistribution of hexobarbital is of minor importance in the present experiments. After different predetermined times of this fairly stable anesthesia, the rats were sacrificed, and concentrations in the cortex of the brain were determined with a HPLC-method. Maximal induction of acute tolerance was seen as a 45 percent increase in cortex concentration after 60 min of anesthesia, but already after 10 min a slight acute tolerance was recorded. PMID- 4015849 TI - Ethanol does not increase lethality due to propoxyphene in rats. AB - Male Wistar rats (210-330 g) were used as test animals. Propoxyphene (175 mg/kg) and ethanol (2 g/kg) were administered by gastric intubation, naloxone (2 mg/kg) by subcutaneous injection. Four groups, each consisting of 19 rats received either of the following drug treatments: Propoxyphene; ethanol + propoxyphene; naloxone + propoxyphene; and naloxone + ethanol + propoxyphene. The drugs were given in the sequence mentioned at the beginning of the experiment. Naloxone was also given 45 and 90 min later. Mortality was reduced to 42% in the group that received ethanol and propoxyphene as compared to 73% in the group that received propoxyphene only. Naloxone protected against lethality in both groups. A rise in the propoxyphene/norpropoxyphene (P/N) ratio due to an increase in the absolute concentrations of propoxyphene and a decrease in the absolute levels of norpropoxyphene in blood, brain and heart tissues was observed in the ethanol + propoxyphene group, compared to the propoxyphene group. Although these pharmacokinetic data indicate impaired propoxyphene metabolism in the presence of ethanol, ethanol did not enhance propoxyphene induced lethality. This is also contrary to suggestions from previous studies. Our results demonstrate that at least in one species and at one dose ratio (ethanol/propoxyphene) ethanol might reduce the lethality caused by propoxyphene alone. This suggests antagonism between the two drugs, probably in the central nervous system. PMID- 4015851 TI - Comparison of ballooned hepatocytes in alcoholic and non-alcoholic liver injury in rats. AB - Ballooned hepatocytes are commonly observed in alcoholic and sometimes in non alcoholic liver diseases. To clarify whether pathogenesis of this change is different in alcoholic and non-alcoholic liver diseases, changes of the livers in rats fed alcohol with pyrazole for 12 weeks were compared with those of CCl4 treated rats. Both groups of rats showed marked ballooning of the hepatocytes in the centrolobular area. Immunohistochemically, the ballooned hepatocytes in alcohol-pyrazole treated rats reacted strongly with transferrin and albumin staining. However, staining reaction of the ballooned hepatocytes in the CCl4 treated rats was slight. In alcohol-pyrazole treated rats, hepatic microtubules were significantly decreased. Retention of transferrin and albumin were found only in the ballooned hepatocytes of alcohol-pyrazole treated rats. However, in the CCl4 treated rats, neither microtubular alteration nor retention of the exportable proteins was observed. These findings indicate that the pathogenesis of ballooning of hepatocytes is different in alcoholic and non-alcoholic liver injuries. In alcoholic liver injury, microtubular alteration may lead to retention of protein and ballooning of hepatocytes by interfering with the hepatic secretion of proteins. PMID- 4015852 TI - Effect of ethanol and aging on histamine release and membranes of mast cells. AB - The effects of ethanol on histamine release from mast cells were compared to ethanol's effects on membrane order of mast cell membranes and synaptosomes in young (6 month) and old (24 month) Fischer 344 rats. Concanavalin A (con A) stimulated histamine release in a concentration dependent manner. Ethanol (10-500 mM) inhibited con A stimulated release while having no effect on nonstimulated release in both young and old rats. Ethanol's effect on membrane order of synaptosomes and mast cell plasma membranes was estimated by measuring the fluorescence polarization of diphenylhexatriene. Ethanol (10-500 mM) decreased the polarization of synaptosomes to the same degree in young and old rats. The polarization of mast cell membranes was also decreased by ethanol but to a greater degree than synaptosomes. The ethanol induced changes in polarization correlated (r2 = 0.99) with ethanol's inhibition of con A stimulated histamine release from mast cells. These findings suggest that mast cells may be more sensitive to membrane disordering by ethanol than synaptosomes. In addition, we have demonstrated that mast cells may be a useful model system for studying ethanol effects on stimulus-secretion coupling. No differences were found between rats 6 and 24 months for histamine release (with or without ethanol) or membrane order of mast cells or synaptosomes. PMID- 4015853 TI - Effects of the maternal consumption of alcohol on alcohol selection in rats. AB - The present study was undertaken to determine the effects of the maternal administration of alcohol on alcohol selection in the adult offspring. Female Wistar rats were pair-fed liquid diets containing either alcohol (6.7% or 4% v/v) or isocaloric carbohydrates starting on day 1 of gestation. The litters were culled to 6 and the pups placed with non-alcohol treated surrogate mothers until they were weaned. At 45 days of age all rats were tested for two-choice selection of 10% (v/v) ethanol vs. water. Consumption from both drinking tubes was recorded for 30 days and selection ratios for alcohol per total fluid volume were calculated. In all conditions a significant increase in alcohol selection was observed across the 30 day test period. These data indicate that prenatal exposure to alcohol may play a part in subsequent selection of alcohol, at least initially. However, the mother's alcohol treatment did not significantly influence the offspring's selection of alcohol over the 30 day test period. Alcohol selection by an individual may be, at least in part, determined by the mother's consumption of alcohol during gestation. PMID- 4015854 TI - The influence of infantile handling, age and strain on alcohol selection in mice. AB - Male mice from three inbred strains (C57B1/10J, BALB/cJ and C3H/2lbg) were assigned to infantile handling or control conditions. In a cross-sectional developmental design, handled and control mice were tested for two-choice selection of 10% (v/v) ethanol vs. tap water at 60, 90 or 120 days of age. The volume of fluid consumed from both tubes was recorded for fifteen days. In 60 day old mice, handling produced a trend toward increased total fluid consumption in the C57 mice and a trend toward increased ethanol selection in the BALBs. In 90 day old mice, there were trends noted toward handling-related decreased fluid consumption in BALBs. Also noted was a trend toward handling related increased ethanol selection in C57 mice. In 120 day old mice, a handling-related increase in alcohol selection was noted in the C3H strain. PMID- 4015856 TI - Brain ALDH as a possible modulator of voluntary ethanol intake. AB - The relationship between voluntary ethanol intake and brain aldehyde dehydrogenase (ALDH) activity was investigated in the laboratory rat. Voluntary ethanol intake was compared to subcellular forms of brain ALDH. Mitochondrial, microsomal and cytosolic fractions were prepared and recovered ALDH activity of each form was compared to voluntary ethanol intake in Long Evans rats. Strong correlations were found between both mitochondrial and microsomal ALDH fractions and ethanol intake. No activity was observed in cytosolic fraction as measured with aromatic or aliphatic aldehydes. In addition, microsomal activity was detected with aromatic aldehydes only, whereas the mitochondrial form would oxidize both aromatic and aliphatic aldehydes. PMID- 4015855 TI - A correlation between voluntary ethanol consumption and brain catalase activity in the rat. AB - The relationship between voluntary ethanol consumption and brain catalase activity was investigated in male Long Evans rats. In the first study, rats which were voluntarily consuming alcohol or water for 25 days were sacrificed by decapitation immediately (group A) or 15 days (group B) following withdrawal of alcohol and their brains analysed for catalase activity. Mean brain catalase activity did not differ among the two groups of rats exposed to ethanol and the ones exposed to water only. Furthermore, there were significant positive correlations between individual voluntary ethanol intake and catalase activity in both groups, (group A:r = .69, p less than or equal to 0.05; group B:r = .54, p less than or equal to 0.05). In the second study, rats were forced to drink high levels of ethanol presented as the only source of fluid for 25 days. Rats were sacrificed and brain, liver, muscle and heart tissue were extracted and analysed for catalase activity. There were no differences in mean brain catalase activity between water and forced ethanol drinking rats indicating that the enzyme was not inducible by high volume ethanol consumption. The results suggest that inherent differences in brain catalase activity may be one of the factors in determining an animal's propensity to voluntarily consume ethanol. PMID- 4015857 TI - [Alcohol and insurance protection]. PMID- 4015858 TI - [Blood sugar in alcoholic intoxication]. PMID- 4015859 TI - [Involvement of chronic alcoholics in road traffic]. PMID- 4015860 TI - [Alcohol kinetics and constitution types with special reference to its modification by food intake. Experimental studies using parenteral alcohol administration]. PMID- 4015861 TI - [Driver's license regulations in the light of the criminal justice compensation law]. PMID- 4015862 TI - [Criteria for environmental hygiene protection in the industrial production of antitumor agents]. PMID- 4015863 TI - [The stability in light of a drop formulation of nifedipine in conditions of therapeutic use]. PMID- 4015864 TI - Spectrophotometric study of drugs containing the 1,4-diazepine-2-thione group. PMID- 4015865 TI - [New beta-chloroethyl derivatives of compounds with interesting pharmacokinetic properties]. PMID- 4015866 TI - [Determination of (trans)-1-[bis(4-fluorophenyl)methyl]-4-(3-phenyl-2-propenyl) piperazine dihydrochloride with HPLC]. PMID- 4015867 TI - In vitro metabolic activation in genotoxicity assays with mammalian cell cultures. PMID- 4015868 TI - [Synthesis and antibacterial activity of azomethino and aminomethyl derivatives of 2,7-dimethoxyquinolin-3-carboxaldehyde]. PMID- 4015869 TI - [Therapeutic effect of coenzyme Q10 in patients with congestive heart failure]. PMID- 4015870 TI - [Comparison of blood levels of oxytetracycline in rabbits treated with a long acting veterinary formulation and a conventional one]. PMID- 4015871 TI - Effects of eye movements on the recognition and localization of dichotic stimuli. AB - Three experiments examined the effect of gaze shifts on overall performance and ear differences in dichotic listening. In the first two experiments, lights were switched on and off so as to induce rightward, leftward, or upward gaze during dichotic stimulation. The dichotic material consisted of musical passages in Experiment 1 and two kinds of verbal material in Experiment 2. Vertical eye movements enhanced the accuracy of identification of music but not verbal material. The lateral direction of eye movements affected subjects' ability to localize targets in Experiment 1: localization was more accurate in the direction toward which subjects were looking. In the third experiment it was found that optokinetic nystagmus (OKN) influenced the asymmetry of performance on a dichotic consonant-vowel (CV) test. The right-ear advantage was greatest when the OKN drum rotated from left to right and least when it rotated from right to left. The effect was due to corresponding variation in left-ear scores. Possible mechanisms through which shifts of gaze affect auditory identification and localization are proposed. PMID- 4015872 TI - Induced lateral orientation and persuasibility. AB - It was hypothesized from three different lines of evidence that relative activation of the left cerebral hemisphere of right-handers would increase resistance to a persuasive message as compared to relative activation of the right hemisphere. An experiment was performed using 22 subjects who heard the counterattitudinal message in only one ear and filled in response measures while their body was turned toward that same side. Subjects who listened and turned toward the left agreed more with the views of the message (p less than .05) and produced more thought favorable to the message (p less than .05) than those induced to orient rightward. It was concluded that these results may be due to asymmetries in selective attention, counterarguing, consistency, self-awareness, and perseveration between the cerebral hemispheres of the normal human brain. PMID- 4015873 TI - Motor and cognitive interference effects on unimanual tapping rates. AB - Experiments conducted on both normal and disordered populations have led to the hypothesis that the left hemisphere's specialization for language results from its control over motor activities. This control is reflected in the lateralized disruption of manual activity during cerebral time-sharing tasks. Recent studies have challenged this hypothesis, stating that the interference effects reflect both cognitive and motor mechanisms in the left hemisphere. This experiment investigates whether the left hemisphere's control over speech involves both of these components or is purely motor. The question was examined by measuring the effect of concurrent hemispheric activity on single-finger tapping rates. Forty subjects tapped under two conditions: speaking and listening. The data show there may be both motor and cognitive mechanisms involved in left-hemisphere control. PMID- 4015874 TI - Perceptual asymmetries in face recognition. AB - Four experiments were carried out to investigate perceptual asymmetries in face recognition. Perceptual asymmetries favoring the half-face on the observer's left were found under free viewing conditions for both unfamiliar faces (Experiment 1) and famous faces (Experiment 3). For unfamiliar faces, this asymmetry was not obtained when fixation was controlled by presenting faces tachistoscopically (Experiment 2). For famous faces, the perceptual asymmetry favoring the half-face normally seen on the left did not appear to be retained in memory (Experiments 3 and 4). Asymmetries in face perception have been explained in terms of a direct access model of laterally effects. However, these results raise the possibility that asymmetric scanning or attentional factors may be important. PMID- 4015875 TI - Spatial-frequency-dependent visible persistence and specific reading disability. AB - Visible persistence duration for sine-wave gratings was measured in 9-year-old normal and specific-reading-disabled children. Experiment 1 investigated the influence of stimulus duration on visible persistence. The results demonstrated a Reading Group X Spatial Frequency interaction with disabled readers showing a smaller increase in persistence duration with increasing spatial frequency than controls. This interaction was greatest with stimulus durations longer than 80 msec. In Experiments 2a and 2b persistence was measured across a range of contrasts from .1 to .5. The stimulus durations employed were 100 msec in Experiment 2a and 300 msec in Experiment 2b. In both experiments, increasing contrast decreased persistence duration at 2 and 12 cycles per degree (c/deg) for the control group. In the specific-reading-disabled group, however, contrast had little effect on the persistence of 2-c/deg gratings in either experiment. In Experiment 2a the persistence of the 12-c/deg grating decreased with increasing contrast for both groups. In Experiment 2b contrast had significantly less effect on persistence duration in the specific-reading-disabled group, however, contrast had little effect on the persistence of 2-c/deg ratings in either experiment. In Experiment 2b contrast had significantly less effect on persistence duration in the specific-reading-disabled group than in the control group at 12 c/deg. Consequently, contrast had less effect on persistence in specific-reading disabled children than in normal readers, especially at durations longer than the "critical duration" for each spatial frequency. Experiment 3 extended this finding to gratings with spatial frequencies of 4 and 8 c/deg. These results indicate a difference between normal and specific-reading-disabled children in cortical visible persistence. Two scores of visual processing were derived from the above experiments. On these scores the reading-disabled children were divided into Visual Disabled Readers (approximately 70%--eight subjects) and Nonvisual Disabled Readers (approximately 30%--four subjects). The percentages of disabled readers in each category remained constant when the sample size was increased to 61 normal and disabled readers. PMID- 4015876 TI - Towards an Australian ophthalmology. The Royal Australian College of Ophthalmologists 16th annual congress, 1984. PMID- 4015877 TI - Development and progression of diabetic eye disease in Newcastle (1977-1984): rates and risk factors. AB - A prevalence study of diabetic eye disease was conducted in Newcastle during 1977 1978. Ophthalmoscopic retinopathy was found in 49% of 1210 clinic diabetics, while vision-threatening retinopathy (VTR) (proliferative signs of maculopathy) occurred in 13%. Maculopathy was the commonest cause of visual loss, occurring frequently in subjects with non-insulin-dependent diabetes. This group has now been followed for up to seven years (including 70% at four years); incidence rates for the development of retinopathy and for progression to a vision threatening stage can now be estimated. The study found that diabetics with no retinopathy developed this at a rate of 8% per year, while only 0.4% per year progressed to VTR. However, once any retinopathy was present, progression to VTR occurred in 6% per year (2% proliferative and 4% maculopathy); and if any retinal signs indicating the presence of capillary closure were noted the rate was 13% per year. These rates are for the group overall: however, certain parameters were found to influence the progression in individual patients. Included were the age at onset and the duration of diabetes, the presence of poor control (particularly in older diabetics on oral agents) or associated nephropathy. An analysis of these data and their implications for routine eye screening of diabetics is presented. PMID- 4015878 TI - Congenital ectropion uveae and glaucoma. AB - Congenital ectropion uveae is a rare condition which may be present in one or both eyes. If the patient is followed glaucoma will always be found to be present. Associated features which have been described are ptosis, Rieger's anomaly, Prader Willi syndrome, facial hemiatrophy and neurofibromatosis. This paper describes a patient followed for 18 years who had bilateral congenital ectropion uveae, bilateral ptosis, asthma and late onset of a dental defect. PMID- 4015879 TI - Clinical experience with the Otago Photoscreener. AB - The Otago Photoscreener provides a sensitive indication of whether or not an infant is able to fix and focus binocularly on nearby objects. This instrument was designed for mass screening to identify infants with strabismus and/or amblyopia who do not fix and focus binocularly. This communication reports the authors' experience with the machine in the diagnosis and treatment of strabismus and amblyopia. PMID- 4015880 TI - Presidential address: Royal Australian College of Ophthalmologists 16th annual congress,1984. PMID- 4015881 TI - Heredity in one hundred patients admitted for excision of pterygia. AB - One hundred consecutive patients admitted to hospital for excision of pterygia were compared with 100 control patients without pterygia. Of the pterygia group 38% had one or more relatives with pterygia, compared with 8% (? 12%) of the control group. Exposure to solar radiation was considered to be similar in both groups. PMID- 4015882 TI - The concurrent application of ophthalmic drops. AB - The significance of the time interval between topical instillation of two different ocular preparations in 63 normal subjects was investigated. The experimental model selected was pupillary dilatation by mydriatic agents. The results indicated that two drugs applied at the "same time" had an equal effect to drugs applied 10 minutes apart. The implications of the study to clinical practice are discussed. PMID- 4015883 TI - Diagnosis and management of lost muscle following strabismus surgery. AB - Of all the complications of strabismus surgery, the lost muscle is one of the most alarming, and yet with patience and careful management it may be one of the most amenable to treatment. This paper reports seven cases of lost muscle following strabismus surgery. In six of the seven cases referred to the Department of Clinical Ophthalmology there had been delay in diagnosis for periods varying from six weeks to 17 years. All the lost muscles were successfully retrieved. With good illumination and magnification and a careful search of the sub-Tenon's capsule space it is unusual to need to explore the orbital fat to retrieve the muscle. PMID- 4015884 TI - Systemic adverse effects of topical ophthalmological drugs: a clinical pharmacologist's view. PMID- 4015885 TI - Presidential address: Royal Australian College of Ophthalmologists 16th annual congress, 1984. PMID- 4015886 TI - [Brain tumors in children]. PMID- 4015887 TI - [Intravenous lidocaine in the treatment of convulsions in infancy]. PMID- 4015888 TI - [Periodic lateralized epileptiform discharges in infants]. PMID- 4015889 TI - [Ultrastructural observation of skin, peripheral blood cells and rectal mucosa in late infantile ceroid-lipofuscinosis]. PMID- 4015890 TI - [Long-term prognosis of convulsive disorders in the first year of life: febrile and afebrile seizures]. PMID- 4015891 TI - [Studies on prenatal factors in childhood epilepsy. Part 1. Clinical aspects]. PMID- 4015892 TI - [Studies on prenatal factors in childhood epilepsy. Part 2. Electroencephalographic aspects]. PMID- 4015893 TI - [Congenital myasthenia associated with skeletal abnormalities and cataract in two sisters]. PMID- 4015894 TI - [Leigh encephalopathy with laminar necrosis of cerebral cortex, neuronal loss in corpus striatum and cerebellar folia; an autopsy case]. PMID- 4015896 TI - [Is Walker-Warburg syndrome a severe variant of Fukuyama type congenital muscular dystrophy (FCMD)?]. PMID- 4015895 TI - [A case of homocystinuria missed by the newborn screening]. PMID- 4015897 TI - [Tay-Sachs disease associated with recurrent appearance of white matter low density by CT scan]. PMID- 4015898 TI - [Membrane potentials and cerebral ischemia]. PMID- 4015899 TI - [Serotonergic effect on cerebrospinal fluid production]. AB - Many details concerning CSF production at the choroid plexus remain unsettled, and the control mechanisms on the production are also not yet clarified. In the present study, the association of serotonin in the dynamics of the CSF production was studied. The authors utilized the ventriculocisternal perfusion method developed by Pappenheimer and an automatic continuous measurement technique which was designed by the authors. The experimental animals comprised 48 mongrel dogs weighing 7.0 to 12.0 kg. The animals were inactivated by intravenous injection of Dialferin after intratracheal intubation for generalized anesthesia with N2O, O2 and Halothane. Within about 2-2.5 hours after starting perfusion of the Blue Dextran-Elliott-B perfusion fluid, the optical density reached a plateau, and the CSF production in the control dogs could be calculated. Once the data for the control had been obtained, intravenous administration of 5-hydroxytryptophan (5 HTP), noradrenaline (NA) and acetazolamide (Diamox) was commenced. Administration of various amount of 5-HTP, a precursor of serotonin, reduced the CSF production, that was, after administration of 10 mg/kg, 20 mg/kg, and 30 mg/kg 5-HTP the CSF production reduced by 37.0 +/- 4.4%, 39.9 +/- 3.1%, and 35.2 +/- 5.5% (mean +/- SD), respectively, and no correlation with dose was observed. After administration of 5-HTP, the blood pressure showed unsteady state for about 10 minutes, showing an increase in pulse pressure. It then declined gradually. All these phenomena were within the range of autoregulation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4015900 TI - [A quantitative study of brain atrophy on computed tomography--multivariate analysis for comparison between the linear measurement method and the pixel count method]. AB - We previously reported the newly developed quantitative measurement of the cerebral atrophy. The data indicated that the volume of the cerebrospinal fluid not always gradually increases during the life course but remains relatively constant until age 50 and thereafter increases with a wide variation. Though the technique, which is called the pixel count method, is highly quantitative, it is quite troublesome as it needs the computer to count out each pixels. On the other hand, the linear measurement method is easier than the pixel count method, but is far less quantitative. We examined seventy four subjects using both the linear measurement method and the pixel count method, and compared them by means of the multivariant analysis. Three different linear measurement methods were selected by the stepwise multiple regression analysis, those are B (distance between the caudate nuclei), E (greatest distance between the lateral ventricles at the level of the cella media) and G (number of visible sulci whose width are more than 3.1 mm at the level of 3 cm above the corpus callosum). B and E were calibrated by the maximum internal width of the skull (H). The highest correlation was achieved with a formula employing these parameters as follows; y = 42.66 X B/H + 12.52 X E/H + 0.232 X G - 2.92 (y means the estimated value of the CCR (CSF-cranial ratio), which is obtained by dividing the CSF volume by the cranial cavity). Multiple correlation coefficient was 0.76, and was statistically significant (p less than 0.001). The authors emphasized that using this formula we can easily predict CCR as the index of the brain atrophy without any computer. PMID- 4015901 TI - [Study of the descending tentorial herniation sign in patients with putamenal hemorrhage at the acute stage]. AB - A sign of descending tentorial herniation (DTH) on computed tomography (CT) in 48 patients with putamenal hemorrhage was examined in the acute stage. Correlation between the DTH sign and prognosis for survival was studied in two groups; a conservative group and an operative group. Patients were grouped according to the presence or absence of DTH sign on CT. Grade 0: no herniation sign; Grade I: an encroachment upon the lateral aspect of the suprasellar cistern (impending herniation); Grade II: widening of the crural and ambient cistern on the same side as hematoma (actual herniation); Grade III: effacement of the cisternal space at the tentorial level (advanced stage of herniation). Twenty-one patients (44%) with Grade 0 DTH sign showed a good prognosis in both conservative and operative groups. Six patients (13%) with Grade I DTH sign also showed a good prognosis in both the conservative and the operative groups except one patient with anisocoria. There were 14 patients (29%) with Grade II DTH sign. Three of them who were treated conservatively showed only mild impairment of consciousness at the initial phase, but became worse 3-4 hours later. In the remaining patients who showed severe impairment of consciousness from the beginning of the illness, prognosis was poor except for patients with hematoma evacuation. Seven patients (15%) with Grade III DTH sign had poor prognosis both in the conservative and the operative groups. It is suggested that, in the acute stage of patients with putamenal hemorrhage, operative procedure should rapidly be performed not only for the clinical herniation sign but also for the DTH sign on CT even if the patients showed no clinical sign and only impairment of consciousness. PMID- 4015902 TI - [Nuclear magnetic resonance study of brain edema in immature rats compared with adult rats]. AB - Traumatic cerebral edema was experimentally produced in immature Wistar strain rats aged 7 days (Group A), and then edematous cerebrums were lyophilized. The water content was measured by the dry weight method. The longitudinal relaxation time (T1) and transverse relaxation time (T2) were measured on the NMR spectrometer. In respect to the measured water content and the relaxation time, changes with time were compared with those in matured rats aged 5 weeks (Group B). In the Group A, the water contents of the gray matter (G), the white matter (W), and the brain stem (BS) increased significantly over the period ranging from 6 to 16 days after the experimental production of cerebral edema. In the Group B, the water contents of G and W also increased significantly one day after the experimental production of cerebral edema. One day after development of the experimental edema, T1 was 1.770 +/- 0.131 sec (G) and 1.752 +/- 0.131 sec (W) in the Group A, while it was 1.451 +/- 0.003 sec (G) and 1.353 +/- 0.011 sec (W) in the Group B. On the other hand, T2 was 96.95 +/- 11.98 msec (G) and 92.80 +/- 8.78 msec (W) in the Group A, while it was 57.90 +/- 1.32 msec (G) and 58.50 +/- 0.98 msec (W) in the Group B. In other words, the relaxation time was significantly prolonged in the Group A. The extent of the prolongation was insignificant in the Group B considering the base line. T2 is assumed to be divided into two components in the cerebral tissues when cerebral edema develops.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4015903 TI - [A case favorably progressed after operation for hypertensive intracerebral hemorrhage showed extravasation on angiogram occurred in chronic alcoholism]. AB - It is said that the prognosis is generally unfavorable in patients with hypertensive intracerebral hemorrhage showed extravasation on angiogram. Recently, we experienced a case whose prognosis was eventful after the removal of hematoma. So we reported this case and discussed between alcoholism and intracerebral hemorrhage accompanied with extravasation on angiogram in this paper. A 59-year-old male was transferred to our emergency center because of right hemiplegia and mild clouding of consciousness at around nine in the evening on December 12, 1983. At the time of admission, his neurological state was classified into grade II, exhibiting the right putamenal hemorrhage and pyramidal destruction type of hematoma by CT scan with 58 ml of hematoma volume. The right carotid angiography was immediately performed and confirmed the hematoma being of lateral type. At that time, extravasation proximal to the lateral lenticulostriate artery was noted. Repeated CT scan revealed the enlarged hematoma (105 ml) accompanying with ventricular hemorrhage. At the completion of these examinations, the neurological grade was III. The hematoma was surgically removed after 4 hours following the onset of cerebral hemorrhage. His postoperative course was very favorable. Although acute hydrocephalus appeared later on, it was cured by ventricular drainage. The patient become possible to walk with a helper by 1 month after operation. CT scan obtained 1 month after operation revealed a remarkable brain atrophy, which was probably derived from chronic alcoholism.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4015904 TI - Effect of hypophysectomy on intestinal phosphate absorption in rats. AB - Intestinal active and passive transport of phosphate (Pi) was studied in hypophysectomized (HX) and intact rats using the in situ intestinal loop technique. Hypophysectomy resulted in a significant reduction of total Pi absorption under active transport conditions. However, when transport data were expressed on the basis of mucosal mass, the reduction was not apparent. Under passive transport conditions, net Pi absorption was lower in the HX rats even after correction for the decrease of mucosal mass. Administration of bovine growth hormone (bGH) did not change the intestinal Pi absorption in the HX rats. These results indicate that a decrease in mucosal mass following hypophysectomy is one of the factors that causes a decrease of intestinal Pi absorption. PMID- 4015905 TI - Strategies for preventing and screening for coronary heart disease. PMID- 4015906 TI - Valve prolapse in Behcet's disease. AB - Valve prolapse was diagnosed solely by echocardiography in three consecutive patients with Behcet's disease. Two patients had prolapse of the posterior mitral valve leaflet, but no clinical manifestations of valve prolapse. In the third patient aortic valve prolapse was associated with physical signs of aortic regurgitation and left ventricular failure. Valve prolapse in these cases may have resulted from structural and functional derangement caused by the underlying non-specific vasculitis that occurs in Behcet's disease. PMID- 4015907 TI - Diffuse non-specific aortitis with multiple saccular aneurysms and aorto-enteric fistula. AB - A rare variant of non-specific aortitis was found at necropsy in a young hypertensive woman. The aorta showed severe, extensive, non-specific aortitis with multiple saccular aneurysms containing thrombi throughout its length except for 2 cm from its bifurcation. A fistulous tract was identified leading from an aortic aneurysm at the level of the renal arteries to the second part of the duodenum. Both renal artery ostia were narrowed. The small intestine contained 2 litres of blood, at necropsy. Bilateral ischaemic atrophy of the kidneys was present. PMID- 4015908 TI - Persistent left sided fifth aortic arch in a neonate. AB - A persistent left sided fifth aortic arch with coarctation of the aorta and persistence of the ductus arteriosus was recognised and treated surgically in a newborn infant. The fifth arch was used to repair the coarctation, and five years later the child had normal peripheral pulses and no residual murmurs. PMID- 4015909 TI - Transient Q waves followed by left anterior fascicular block during exercise. AB - A 45 year old white man developed transient abnormal Q waves and ST segment elevation preceding left anterior fascicular block during exercise stress testing. The simultaneous disappearance of Q waves and fascicular block suggested that the abnormal Q waves were determined by an early septal conduction defect. PMID- 4015910 TI - Rupture of the myocardium. Occurrence and risk factors. AB - The occurrence of myocardial rupture was studied in a well defined unselected population of patients with acute myocardial infarction, and the group of patients who died of rupture of the heart were compared with two control groups. Of a total of 3960 patients, 1746 (44%) fulfilled the diagnostic criteria for acute myocardial infarction. Rupture was defined solely on the basis of the presence of a pathological passage through part of the myocardium, either the free wall of the left ventricle or the septum, found at necropsy or during operation. Two controls were selected for each patient and matched for age and sex, one (control group A) with acute myocardial infarction having died in hospital but not of rupture (non-rupture cardiac death) and one (control group B) with acute myocardial infarction having survived the hospital stay. Necropsy was performed in 75% of all fatal cases with acute myocardial infarction. The total hospital mortality was 19%, the highest mortality being among women over 70 years (29%). Ruptures (n = 56) were found in 17% of the hospital deaths, or 3.2% of all cases of acute myocardial infarction. Women aged less than 70 had the highest incidence of rupture, 42% of deaths being due to rupture. The mean age for patients with rupture and controls was 70.5 years. The median time after admission to death was approximately 50 hours for patients and control group A. Thirty per cent of the patients with rupture occurred within 24 hours of the initial symptoms occurring. Angina and previous acute myocardial infarction were more common among control group A. Patients with rupture and control group B were mostly relatively free of previous cardiovascular or other diseases (chronic angina pectoris ( > 2 months) and previous myocardial infarction). Sustained hypertension during admission to the coronary care unit was more common in patients than in control group A. Hypotension and shock were more common among control group A. Most (79%) of the patients who subsequently ruptured did not receive any corticosteroids at all during the hospital stay. Severe heart failure and antiarrhythmic treatment were more uncommon among patients than among control group A. Patients with rupture received analgesics approximately three times a day throughout their stay. Control group B received analgesics mostly during the first 24 hours. Thus female patients, patients with first infarcts, and patients with sustained chest pain should be investigated for the possibility of rupture. As many as one third (32%) of ruptures may be subacute, and therefore time is available for diagnosis and surgery. PMID- 4015911 TI - Anomalous origin of the left coronary artery from the pulmonary artery in an adult. AB - Anomalous origin of the left coronary artery from the pulmonary artery is a rare, almost universally fatal form of congenital heart disease. A case was diagnosed in a 19 year old woman who had exercise induced syncope and ST segment displacement during exercise stress testing. The anomaly was successfully treated with ligation of the anomalous left coronary artery combined with saphenous vein grafting. Young adults with exercise induced syncope should be examined by exercise stress testing, and if it induces ST segment displacement coronary angiography should be undertaken. PMID- 4015912 TI - How important is a history of chest pain in determining the degree of ischaemia in patients with angina pectoris? AB - Since therapeutic decisions in patients with angina pectoris are usually based on the reported frequency of exertional and rest pain the relations between the historical frequency of chest pain and objective evidence of myocardial ischaemia during normal daily activity were investigated in 100 patients by 48 hour ambulatory ST segment monitoring. Of these 100 consecutive patients with chest pain, 91 had typical pain and nine some atypical features. Twenty six patients had normal coronary arteries and 52 of the 74 with significant coronary disease had ambulatory ST segment changes. There was no relation between the frequency of reported exertional or rest pain and (a) the severity of coronary artery disease or (b) the frequency of daytime or nocturnal ST segment changes. Twelve patients had nocturnal ST segment changes but only four complained of nocturnal angina. Most patients had both painful and painless episodes of ST segment changes, but a substantial number had either painless or painful episodes only. These differences were not related to the severity of coronary artery disease. Chest pain after the onset of ST segment change was perceived with wide interpatient and intrapatient variability. Thus the frequency of pain is a poor indicator of the frequency of significant cardiac ischaemia. Individual differences in the perception of pain may be more important. PMID- 4015913 TI - Ischaemic heart disease and prodromes of sudden cardiac death. Is it possible to identify high risk groups for sudden cardiac death? AB - A study was carried out to determine the incidence of sudden cardiac death in a well defined population in relation to prodromes, medical history, and previous medical consultations before sudden cardiac death. In Frederiksborg county, Denmark (population 332 000), of 1309 consecutive deaths in a six month period, 166 were due to sudden cardiac death; among men aged 50-69, 22% of all deaths were due to sudden cardiac death. The incidence per 1000 population per year by age group (less than 50, 50-69, greater than or equal to 70 years) was 0.19, 3.6, 11.4 in men and 0.12, 1.0, and 6.4 in women. The increasing incidence with age was significant. Ischaemic heart disease or hypertension had been recorded in 75% (124/166) of patients. Prodromes were reported in 54% (38/71) of patients with angina, and in 26% (25/95) without. Nineteen per cent (32/166) had neither prodromes nor overt heart disease. Forty six per cent of patients with known ischaemic heart disease and 24% without had consulted a doctor less than four weeks before death. Eight per cent had had a myocardial infarction within a year of death. PMID- 4015914 TI - Milrinone in heart failure. Acute effects on left ventricular systolic function and myocardial metabolism. AB - Milrinone, a new bipyridine compound related to amrinone, is a potent non adrenergic inotrope in experimental preparations and also shows vasodilator activity. In the present study the haemodynamic and metabolic effects of milrinone were evaluated in 12 patients with congestive heart failure. Milrinone 5 mg given orally produced a sharp reduction in left ventricular end diastolic pressure without significantly affecting stroke volume. The improvement in left ventricular function was due to a combination of vasodilation and positive inotropism. Thus small reductions in blood pressure and systemic vascular resistance were associated with increments in the isovolumic indices of left ventricular function. The relation between left ventricular end systolic pressure and dimension was displaced leftwards and downwards. Only reductions in left ventricular cavity dimension were statistically significant, however. Though myocardial oxygen consumption did not change significantly, it tended to increase whereas lactate consumption tended to decrease. This trend towards oxygen imbalance suggests the need for caution in the use of milrinone in patients with severe coronary artery disease. PMID- 4015915 TI - Milrinone in heart failure. Effects on exercise haemodynamics during short term treatment. AB - The effects of milrinone, a new bipyridine inotropic agent, on the haemodynamic responses to treadmill exercise were studied in 12 patients with congestive heart failure. Four weeks' treatment with milrinone 20 mg daily produced an improvement in left ventricular function during exercise as reflected by significant increments in cardiac index and stroke volume index without change in pulmonary capillary wedge pressure. Systemic oxygen consumption, measured at submaximal exercise, also increased suggesting that the drug induced rise in stroke output was associated with improved skeletal muscle perfusion. Maximum exercise capacity increased. Importantly, the beneficial effects of milrinone on exercise haemodynamics and exercise tolerance were sustained throughout the four week treatment period. No drug related side effects occurred. After treatment with milrinone was stopped left ventricular function deteriorated to a level slightly, but significantly, worse than that before treatment. These observations indicate a potentially useful role for milrinone in treating heart failure. PMID- 4015916 TI - Localisation of ventricular septal defects by simultaneous display of superimposed colour Doppler and cross sectional echocardiographic images. AB - Precise non-invasive localisation of the site of a small ventricular septal defect was attempted using a new technique that simultaneously combines conventional cross sectional echocardiography with a Doppler system by superimposing the colour coded direction and velocity of blood flow directly on to real time ultrasound images. Twenty three patients with unoperated ventricular septal defects and a further eight after surgical closure were studied; 12 children with normal hearts served as controls. A colour coded blood flow jet entering the right ventricle during systole was identified in all 23 unoperated patients, in 11 of whom the defect was too small to be visualised by conventional cross sectional echocardiography. The colour Doppler technique precisely located 19 perimembranous and five trabecular defects (one patient had two defects). Five of the postoperative patients were without clinical evidence of a significant shunt but had pansystolic murmurs. In each of these five, trans-septal shunt blood flow as demonstrated by colour Doppler images whereas in only three of these patients was the residual defect large enough to be visualised by conventional cross sectional echocardiography. Three postoperative patients had no murmurs and showed no residual shunt on colour Doppler images. This was confirmed at cardiac catheterisation. There were no false positive results among the controls. This technique is useful for the more accurate diagnosis and location of ventricular septal defects and may help in assessing their natural or surgical closure. PMID- 4015917 TI - Myocardial infarction and thrombolysis. Electrocardiographic short term and long term results using precordial mapping. AB - In a consecutive series of 56 patients with acute myocardial infarction, ST segment depression and elevation in the electrocardiographic limb leads I, II, and III were summated for each patient before and immediately after intracoronary streptokinase infusion and the results compared with the angiographic findings. Forty three patients had angiographically confirmed reperfusion of an initially occluded vessel and showed a significant decrease in summated ST shift. The ST segment changes in the limb leads virtually returned to normal in all 43 patients, and in most, inverted T waves developed. Thrombolysis was unsuccessful in 10 patients, and the infarct related coronary artery was already patent in three. When these two groups are combined, all 13 patients without reperfusion showed no significant change in summated ST segment shift. During percutaneous transluminal angioplasty inflation of the balloon in the vessel that was previously occluded simulated reocclusion and was followed by new ST elevation if the artery supplied viable myocardium. In a further consecutive study of 54 patients with anterior myocardial infarction, the precordial R waves and Q waves were studied over the four to six months following infarction using a standardised 48 electrode mapping system. All patients underwent a repeat angiogram after four to six months. In 36 patients the infarct related vessel was patent. They showed a significant mean increase in summated precordial R wave amplitude and a reduction in the mean number of precordial leads without R waves. In 18 patients with unsuccessful thrombolysis or reocclusion there was a further reduction in mean summated R wave amplitude and an increased number of precordial leads not showing R waves. Precordial R wave mapping seems to be a valuable non invasive method of assessing the salvage of myocardium after reperfusion and the damage caused by reocclusion. Loss of R waves in the acute phase of myocardial infarction does not necessarily mean an irreversibly damaged myocardium. PMID- 4015918 TI - Cross sectional echocardiographic and angiocardiographic correlation in criss cross hearts. AB - Cross sectional echocardiography can provide accurate anatomical diagnosis in congenital heart diseases and therefore should be able reliably to identify criss cross hearts and enable the analysis of their sequential arrangement non invasively. The cross sectional echocardiographic diagnoses in eight consecutive patients with this condition were compared with those made at cardiac catheterisation and cineangiocardiography (five retrospectively, three prospectively). The mean number of invasive studies required to reach the diagnosis was 1.9 (range 1-4). Complete anatomical diagnosis was achieved with cross sectional echocardiography in all patients, but identification of ventricular morphology was much more straightforward using cineangiocardiography. If the transducer was held steady in either a precordial or subcostal position and rocked anteriorly and posteriorly the characteristic crossing over of the ventricular inflows could easily be seen. In no plane was there normal parallel arrangement of ventricular inflows. A complete diagnosis should be possible in these patients using cross sectional echocardiography in experienced hands and at a single session in the cardiac catheterisation laboratory. PMID- 4015920 TI - Effect of exercise on ventricular response to atrial fibrillation in Wolff Parkinson-White syndrome. AB - Ten patients with Wolff-Parkinson-White syndrome underwent cardiac electrophysiological study extended to include the induction of atrial fibrillation at maximum exercise in the upright position. This was performed using a new temporary bipolar lead with a helical active fixation tip for atrial pacing. The highest rate of atrioventricular conduction via the accessory pathway was greater during exercise than at rest in all 10 patients (mean increase 28%). In three cases the resulting ventricular rate exceeded 300 beats/min, but no patient had severe symptoms or ventricular arrhythmias. The exercise induced enhancement of accessory pathway conduction may significantly but unpredictably affect the risk from spontaneous atrial fibrillation especially in patients with coronary artery disease or in those taking antiarrhythmic drugs. The test procedure was sufficiently simple and well tolerated to be included in our routine electrophysiological investigation. PMID- 4015919 TI - Evaluation of an elliptical area technique for calculating mitral blood flow by Doppler echocardiography. AB - To evaluate a method for measuring blood flow through the mitral valve 18 normal subjects and 19 patients with cardiac disease in whom mitral and aortic blood flows were identical were studied. Initially the mitral ring area was planimetered from the echocardiographic image, but the results of area calculation using the mathematical formula for the area of an ellipse were found to approximate to within 8% of the planimetered result in most cases. The formula was therefore used if the ring appeared elliptical on the cross sectional echo image, and other shapes were planimetered. Mitral velocity, aligned with flow in three planes, was recorded just distal to the ring. Mitral flow calculated using the elliptical technique correlated closely with flow measured in the ascending aorta by the Doppler technique and also with systemic flow measured by the Fick method at cardiac catheterisation in 10 patients. The mitral flow technique that assumed a circular orifice correlated almost as well with Doppler aortic flow and with Fick flow but overestimated flow by a mean of 1446 ml, whereas the elliptical method had a mean error of only 138 ml. Both methods correlated well with standards, but the elliptical method was easy to apply and gave a better correlation with comparison reference values. PMID- 4015921 TI - The challenge and the reproach of infective endocarditis. PMID- 4015922 TI - Do we need a new standard for electrocardiographs? PMID- 4015923 TI - Artefactual ST segment abnormalities due to electrocardiograph design. AB - Specifications recommended for electrocardiographs omit any reference to phase characteristics and place undue emphasis on an extended amplitude response. This does not, however, ensure faithful reproduction of the electrocardiogram and may result in less effective attenuation of unwanted noise than can be achieved with modern filters. The separate effects of phase and amplitude response on electrocardiographic signals were compared, and it was shown that distortion of the electrocardiogram by equipment with an inadequate phase response may cause changes resembling those seen in ischaemic heart disease. Case reports are presented in which distortion produced by commercial equipment impeded diagnosis. Specifications recommended as standard for electrocardiographs should be modified to include phase response and allow greater attenuation of frequencies below 0.5 Hz. PMID- 4015924 TI - Prevalence of overt dilated cardiomyopathy in two regions of England. AB - The prevalence of dilated cardiomyopathy was assessed in two regions in England from 420 replies to 771 questionnaires sent to general practitioners. Overall point prevalence was 8.317 per 100 000 population in areas covering a total sample of 913 836 inhabitants. There was a statistically significant regional variation between East Anglia (Norfolk, Suffolk, and Cambridgeshire) and Essex, Hertfordshire, and Bedfordshire. Though the natural history of dilated cardiomyopathy remains to be defined, this study has provided an assessment of point prevalence of overt cases of this condition. PMID- 4015925 TI - Familial right ventricular dilated cardiomyopathy. AB - Cardiomyopathy of unknown cause occurred in three of six siblings. The course of the illness was marked by life threatening supraventricular and ventricular arrhythmias, sinoatrial block, atrioventricular block, and embolism (in one patient). The disease was characterised by right ventricular dilatation. Two of the three patients died aged 32 and 48. No new cases of the disease were found when a further 33 family members from three generations were investigated. PMID- 4015926 TI - Role of echocardiography in differential diagnosis of broad complex tachycardia. AB - It is not always easy to distinguish between supraventricular tachycardia with aberration and ventricular tachycardia by electrocardiographic analysis alone. M mode echocardiography can often help by providing direct or indirect evidence of the relation between atrial and ventricular contraction. Sixteen consecutive patients with spontaneous sustained broad QRS complex tachycardia with heart rates of 120-225 beats/minute were examined. Echocardiographic evidence of 1:1 conduction was seen in three cases and 2:1 atrioventricular conduction in one (all four had supraventricular tachycardia, confirmed by intracardiac electrocardiography in three). Evidence of retrograde block was seen in 12 (all had ventricular tachycardia, with electrophysiological confirmation in 10). Satisfactory views of the mitral valve were obtained in all patients. Patients with ventricular tachycardia had a variable mitral valve opening time (range 42 110%) compared with those who had supraventricular tachycardia (9-15%). Aortic root and left atrial views gave direct evidence of atrial contraction in three cases, and subcostal right atrial wall views were diagnostic in four of five cases. Seven patients with ventricular tachycardia had been wrongly diagnosed elsewhere as having supraventricular tachycardia. This study confirms that echocardiography is a simple and rapid aid to accurate diagnosis in patients with broad QRS complex tachycardia. PMID- 4015927 TI - Prevalence and clinical significance of aortic valve prolapse. AB - The prevalence and clinical significance of aortic valve prolapse were determined prospectively in 2000 consecutive patients undergoing routine clinical cross sectional echocardiography. Two hundred and twelve patients were excluded because the aortic cusps were not adequately visualised. Aortic valve prolapse was defined as downward displacement of cuspal material below a line joining the points of attachment of the aortic valve leaflets. Twenty four cases of aortic valve prolapse (1.2%) were identified. The patients were aged 12-64 years and nine were women. All had underlying valvar heart disease and the commonest lesion (in 11 cases) was prolapse of the larger cusp in bicuspid valves. Aortic valve prolapse was seen in four patients with mitral valve prolapse (two with severe regurgitation), one of whom had marfanoid aortic root dilatation. The remaining examples of aortic prolapse were seen in patients with various disorders including one with pulmonary atresia, two with aortic root disease (one with dissection and one with idiopathic dilatation), and one case of severe mitral regurgitation. Valves destroyed by infective endocarditis were seen in two cases. Aortic valve prolapse may be detected in various cardiac disorders and does not imply the presence of aortic regurgitation, but when bicuspid aortic valves are present it may well be important in producing such regurgitation. Although aortic valve prolapse may be associated with severe forms of mitral valve prolapse, these patients rarely have aortic regurgitation. PMID- 4015928 TI - Embolisation procedures in congenital heart disease. AB - Eight therapeutic embolisation procedures were performed by the transcutaneous catheter technique in seven patients with congenital heart disease. After surgical correction of tetralogy of Fallot (four patients), catheter embolisation was used to occlude two large aortopulmonary collaterals (one patient), three small aortopulmonary collaterals (one patient), and two Blalock-Taussig shunts (two patients). In two patients congenital coronary anomalies were occluded--a coronary arteriovenous malformation and a coronary artery/bronchial artery anastomosis. In one patient a pulmonary arteriovenous malformation was embolised. Detachable balloons were used to occlude six large arteries, the three small arteries were occluded with small gelfoam fragments, and the pulmonary arteriovenous malformation was occluded with multiple steel coils and large gelfoam pieces. Successful occlusion was achieved in all cases. No complications were encountered and the procedure was well tolerated even in the two patients receiving postoperative intensive care. Therapeutic embolisation in suitable cases is a safe and effective alternative to surgery and the detachable balloon technique is effective in occluding high flow vessels. PMID- 4015929 TI - Functional and anatomical correlates in atrial septal defect. An echocardiographic analysis. AB - The results of cross sectional echocardiography, intracardiac contrast echocardiography, and balloon sizing techniques and conventional haemodynamic assessment were correlated in 40 consecutive patients evaluated for an isolated left to right shunt at atrial level. Echo free areas along the septum were identified in 23 of 25 patients with a secundum defect, but not in two with a fenestrated defect, and in the upper atrial septum in three of four patients with a sinus venosus defect. No false positive results occurred in 11 patients with a probe patent foramen ovale. Saline contrast injection into the left atrium showed significant left to right shunting in all patients with atrial septal defect; inferior vena caval injection produced right to left shunting in 15 of 29 patients and a negative contrast effect in eight of 29 patients with an atrial septal defect, although neither correlated quantitatively with defect diameter or magnitude of the left to right shunt. Echocardiographic assessment of defect size as small, moderate, or large showed a highly significant correlation with balloon measurement of defect diameter, although some overlap between the groups was evident. In contrast, the correlation between defect diameter and pulmonary to systemic blood flow ratio was poor, mainly because of highly variable shunting in patients with an anatomically large defect. Cross sectional echocardiography has high sensitivity and specificity in the diagnosis of the non-fenestrated atrial septal defect and provides quantitative information about defect diameter. Contrast studies do not add to the diagnostic value of imaging from the subcostal position. The poor correlation between defect size and the measured shunt suggests that the latter may not be the best criterion for surgical management and that size could be an important factor likely to influence both the long term prognosis and the decision for closure. PMID- 4015930 TI - Left ventricular outflow tract obstruction in complete transposition of the great arteries with intact ventricular septum. A cross sectional echocardiography study. AB - The roles of posterior bulging of the interventricular septum (septal bulge) and of systolic septal mitral apposition in patients with simple transposition of the great arteries are not known. Cross sectional echocardiograms of 40 such patients were reviewed (after exclusion of those with fixed left ventricular outflow tract obstruction) and haemodynamic findings were compared with long and short axis measurements within the left ventricle. There was no significant correlation between the degree of septal bulge and systolic gradient across the left ventricular outflow tract, but septal bulge correlated weakly with systolic right ventricular pressure and inversely with pulmonary arteriolar resistance index. Systolic left ventricular outflow gradient was inversely related to the minimum systolic distance between the anterior mitral leaflet and interventricular septum. No patients without complete systolic apposition of the anterior mitral leaflet and interventricular septum had a left ventricular outflow gradient greater than 20 mm Hg. Conversely, even when cross sectional echocardiography showed apparently total obstruction of the left ventricular outflow tract at some time in systole there was often no significant gradient detected during haemodynamic study. In the short axis cuts closeness of the papillary muscles to the interventricular septum or to each other was unrelated to systolic gradient. This study shows that (a) cross sectional echocardiography can identify fixed obstruction of the left ventricular outflow tract in simple transposition of the great arteries; (b) the degree of septal bulge, unless complicated by fibrous thickening of the anterior mitral leaflet and interventricular septum, is unrelated to the gradient across the left ventricular outflow tract; (c) the absence of systolic septal/mitral apposition excludes a significant gradient at that site across the left ventricular outflow tract; and (d) papillary muscle geometry is unrelated to dynamic gradients across the left ventricular outflow in this condition. PMID- 4015931 TI - Fluid removal by haemofiltration in diuretic resistant cardiac failure. AB - A 60 year old woman with diuretic resistant cardiac failure was treated with intermittent haemofiltration before tricuspid valve replacement. This technique can remove large quantities of fluid rapidly, thus controlling oedema and allow appropriate fluid replacement. Haemofiltration is thus a simple and safe method of managing unresponsive oedema in cardiac failure sometimes allowing corrective cardiac surgery. PMID- 4015932 TI - Permanent pacemaker failure due to surgical emphysema. AB - A 76 year old man developed a left pneumothorax after implantation of a permanent endocardial pacemaker via the left subclavian vein. The resulting surgical emphysema caused temporary failure of the pacing system. PMID- 4015933 TI - Chronic nicotine ingestion and atrial fibrillation. AB - Paroxysmal atrial fibrillation occurred in a fit 35 year old man who consumed large doses of nicotine chewing gum (Nicorette Leo) over a prolonged period. PMID- 4015935 TI - Relative potency of agonist and partial agonist opioids. PMID- 4015936 TI - Bronchospasm and hypotension following cardiopulmonary bypass. PMID- 4015934 TI - Changing echocardiographic features of a hydatid cyst of the heart. AB - A 24 year old woman with pulmonary embolism and a past history of echinococcal disease underwent echocardiography which detected two cysts in the right ventricle which became more solid after treatment with mebendazole. The surgical and pathological findings confirmed the presence of the two cysts and the hydatid nature of the lesion. PMID- 4015937 TI - Comparison of the efficacy of chlormethiazole and diazepam as i.v. sedatives for supplementation of extradural anaesthesia. AB - The clinical efficacy of two sedative agents was compared in 21 young healthy patients undergoing surgery under extradural blockade. A state of sedation and amnesia in which patients lapsed into a sleep-like state when left undisturbed, yet spontaneously opened their eyes to make comments and co-operate with verbal commands, was sought. This was achieved readily by careful titration of responses and required a diazepam loading dose of 20 (+/- 15) mg given at a rate of 1 mg min-1 or 0.8% chlormethiazole edisylate infusion 10 ml min-1 given over 16 (+/- 6) min. Control of this state was easier with chlormethiazole (by varying the rate of infusion) than by giving repeated doses of diazepam. Both agents provided good anterograde amnesia; there was no retrograde amnesia. Considerable postoperative somnolence with a high incidence of relapse into amnesic and sedated states were noted with both agents. However, if the total volume of chlormethiazole infused was less than 300 ml, then a distinct advantage of abrupt and lucid recovery was apparent. Blood concentrations producing the desired clinical state were more variable for diazepam than for chlormethiazole. PMID- 4015938 TI - Measurement of plasma catecholamine concentrations. An assessment of anxiety. AB - This study was designed to assess the value of measurement of plasma catecholamine concentrations as an objective index of anxiety. A preliminary study was undertaken on 11 healthy volunteers (medically qualified), to determine if venous cannulation per se produced any change in plasma catecholamine concentrations. There were no changes in plasma catecholamine concentrations in the 2 h following insertion of an i.v. cannula, suggesting that venous cannulation did not induce a measurable stress response. A second study was performed on 48 surgical patients who were asked to rate their perceived anxiety on a linear analogue scale immediately before premedication and immediately before induction of anaesthesia. Venous blood was obtained at the same time as these ratings. There were no significant changes in perceived anxiety or plasma noradrenaline concentrations following premedication. However, compared with values before premedication, there was a mean percentage increase in plasma adrenaline concentration of 40% before induction of anaesthesia. A significant correlation was shown between mean percentage change in Linear Analogue Anxiety Score and mean percentage change in plasma adrenaline concentrations (r = 0.32). PMID- 4015939 TI - Determination of the partial pressure of halothane (or isoflurane) in blood. AB - A gas chromatographic method is described for the direct quantitative determination of the partial pressure of halothane (or isoflurane) in blood as well as the blood-gas partition coefficient. A head space technique and a flame ionization detector were used. Standard blood was obtained by equilibrating patients' blood with known gas concentrations in a tonometer. Using an infra-red analyser to measure the halothane gas concentration in the tonometer and within the anaesthetic system allowed for the direct comparison of the partial pressure in blood to the partial pressure in the inspired gas. Technical problems associated with this procedure, and with comparable methods, are discussed. PMID- 4015940 TI - The minimum reservoir capacity necessary to avoid air-dilution. An experimental model of spontaneous breathing through a T-piece. AB - The fresh gas flow rate necessary to prevent rebreathing in T-piece anaesthesia is well established at twice total ventilation. The minimum reservoir volume to avoid air dilution of anaesthetic gases in the alveolus at this flow rate is, however, undecided. A lung model was constructed to represent spontaneous respiration, and the value of minimum reservoir volume as a proportion of tidal volume determined experimentally. The values so obtained were in close accord with those calculated theoretically. Extension of the theoretical analysis leads to a recommendation that a reservoir volume one-third that of tidal volume, as originally suggested by Ayre in 1956, will prevent air-dilution. PMID- 4015941 TI - Proceedings of the Anaesthetic Research Society. Leicester, March 22-23, 1985. Abstracts. PMID- 4015942 TI - Is Urografin anti-anaesthetic. PMID- 4015943 TI - Follow-up visit after acute otitis media. PMID- 4015944 TI - Double carcinoid of the gastrointestinal tract. PMID- 4015945 TI - Anorexia nervosa and Crohn's disease. PMID- 4015946 TI - Bell's Palsy associated with hypothyroidism. PMID- 4015947 TI - Intra abdominal lipoma. PMID- 4015948 TI - Hutchinson's melanotic freckle melanoma and the use of non-permanent hair dyes. PMID- 4015949 TI - Continuous 5-day regional chemotherapy by 5-fluorouracil in colon carcinoma: pharmacokinetic evaluation. AB - Eighteen patients with liver metastasis or locoregional recurrence of colon carcinoma received locoregional treatment by continuous 5-day infusions of 5-FU. 5-FU blood levels were measured by HPLC every day of the cycle at 8 am and 5 pm for a total of 87 cycles. Twelve patients were given the drug by an intra arterial hepatic (i.a.h.) route, 3 by the portal vein (i.p.v.) and 3 by an intra arterial pelvic (i.a.p.) route. These three routes were compared in respect of their relative pre-systemic drug uptake and the effect of dose escalation. Both the i.a.h. and i.p.v. routes, but not the i.a.p. route, resulted in a significant reduction in AUC 0-105 h compared to the i.v. route at the same dose range. Increasing the dose led to a modification in circulating 5-FU levels proportional to the dose for the i.v. and i.a.p. routes. By contrast, for the i.a.h. and i.p.v. routes, systemic drug delivery was significantly elevated, out of proportion with the dose, indicating a saturable process. For the i.a.h. route, increasing the 5-FU dose from 780 to 1000 mg m-2 day-1 caused a drop in hepatic extraction from 0.93 (0.90-0.95) to 0.44 (0.21-0.66). Liver saturation mechanisms were also evidenced by a mean increase of 2.6 times for the circulating drug level during the second part of the cycle as compared to the first part (P less than 0.001). The evolution of 5-FU AUC 0-105 h as a function of the dose was exponential (r = 0.75, P less than 0.001). Local extraction consecutive to i.a.p. was non-existent, implying that this route of drug administration has no potential advantage over classical i.v. infusion. PMID- 4015950 TI - Effective inhibition by low dose aminoglutethimide of peripheral aromatization in postmenopausal breast cancer patients. AB - Aminoglutethimide without glucocorticoid has been shown to be a clinically effective treatment for postmenopausal breast cancer in low dosage (250 mg day 1). The mechanism of action of this approach is thought to be the inhibition of peripheral aromatase, the enzyme which converts androstenedione to oestrone. The activity of this enzyme was measured in vivo by injection with 3H-androstenedione and 14C-oestrone and found to be 0.20% +/- 0.05 in 5 patients on low dose AG therapy. In comparison with previously published data this demonstrates a 92% inhibition of peripheral aromatase activity confirming aromatase inhibition as a viable aim in the endocrine treatment of breast cancer. PMID- 4015951 TI - Antitumour imidazotetrazines, Part IX. The pharmacokinetics of mitozolomide in mice. AB - Mitozolomide is a novel antitumour agent showing a broad spectrum of activity against murine tumours and is currently undergoing Phase I clinical evaluation in the UK. We have conducted an animal pharmacokinetic study using male BALB/c mice as a pre-requisite to the clinical work. Mice were dosed i.p. at 5 dose levels (0.25-20 mg kg-1) and the oral and transdermal routes of administration were investigated at 20 mg kg-1. The analytical data produced a good fit to a simple open one-compartment pharmacokinetic model with an elimination half-life of the drug from plasma of between 0.68 and 0.88 h over the 0.25-20 mg kg-1 range covered. There was no evident dose dependency over this range and studies with two formulations showed mitozolomide to have good systemic availability when administered via the oral route (F values of 0.66 and 0.81). The drug was also found to be systemically available when administered topically in dimethylsulfoxide (F = 0.47). Mitozolomide shows many biochemical and biological similarities to the clinically used nitrosoureas BCNU and CCNU but our results show that it differs markedly in its kinetics from these two agents, with mitozolomide having relatively sustained plasma levels. It is hoped that this may be of therapeutic benefit if these levels are reflected in relative tumour concentrations. PMID- 4015952 TI - Thermal sensitivity of haemopoietic and stromal progenitor cells in different proliferative states. AB - Stromal progenitor cells (CFU-F) in normal mouse bone marrow were more sensitive to heat at 43 degrees C than haemopoietic progenitor cells (CFU-S and GM-CFC) by a factor of approximately 1.2. In marrow regenerating after 4.5 Gy X-rays, the changes in sensitivity were by less than a factor of 1.4 and the sensitivity of CFU-F changed slightly to become intermediate between that of CFU-S and GM-CFC. A comparison of sensitivities reported in the literature revealed an inexplicable large variation of up to a factor of 6 in the thermal sensitivities of CFU-S and GM-CFC. PMID- 4015954 TI - Serum cholesterol and primary brain tumours: a case-control study. AB - The objective of this study was to test the hypothesis that a positive relationship exists between high levels of serum cholesterol and primary brain tumours. A record-based case-control study was performed on male Jewish residents of Israel who were hospitalized at the Hadassah Ein Karem hospital in the years 1978-1982. A record check identified 37 cases of brain tumour who fulfilled the criteria for inclusion in the study and whose hospital files included the necessary data. For each case two controls were chosen randomly from all patients with inguinal hernia who met the respective matching criteria of age and year of hospitalization. The mean cholesterol value of the cases with brain tumours was 22 mg dl-1 higher than that of the controls. This difference was statistically significant (P = 0.007). Controlling for weight, region of birth, season of year, social class, medications and length of hospitalization before the measurement of cholesterol did not reduce the cholesterol difference, and in some instances increased it. PMID- 4015953 TI - Specificities and binding properties of 2 monoclonal antibodies against carcinoma cells of the human urinary bladder. AB - Mice were immunized with cultured cells derived from transitional cell carcinoma of the human urinary bladder (TCC). Spleen cells were fused with mouse myeloma cell line Sp2/0-Ag14 and the hybridomas obtained screened for antibody production against a panel of human cells. Two hybridomas were selected for further studies. The antibodies from one of these hybridomas (P7A5-4) could clearly discriminate between malignant and normal cells from the bladder, both when tested with cultured cells and fresh tissue. The P7A5-4 antibodies, however, also reacted with some non-TCC cultured carcinoma and melanoma cells but to a lesser extent. This difference in reactivity was even more pronounced in the fresh tumours tested, thus indicating a quantitative difference in antigen expression between TCC and other cells. From extracts of TCC cells, P7A5-4 bound three polypeptides of mol. wts 92Kd (ConA+), 23 and 17Kd (ConA-). The antibody derived from hybridoma SK4H-12 bound a ConA reactive glycopeptide of 100Kd mol. wt, the expression of which was almost entirely restricted to urothelial cell lines and tissue of TCC origin, as shown by immunocytochemical studies. The finding in this study of new antigens associated with urinary bladder carcinoma, extend the results obtained previously in our laboratory (Koho et al., 1984; Paulie et al., 1984) and further delineate the heterogeneity of tumour-associated antigens in this human tumour system. PMID- 4015956 TI - Are asthma mortality rates changing? AB - Published asthma death rates have risen during recent years. This may be due to a number of possible factors and it is important to assess whether or not the increase is genuine. Evidence from the BTA confidential enquiry into asthma deaths together with the results of bridge coding by the Office of Population Censuses and Surveys suggest that published death rates in the 15-44 year age group are reasonably accurate and comparisons before and after recent changes in the International Classification of Diseases are valid. The death rate in females in this age group has almost halved since the pre-epidemic levels of the 1960s, whereas the rate for males is little changed. This should alert all those involved in the management of severe acute asthma to the seriousness of the problem that remains. PMID- 4015955 TI - Long-term survival in 406 males with breast cancer. AB - Survival was analyzed during a follow-up period of up to 20 years in 406 (97%) of all 420 males in whom breast cancer was diagnosed in Sweden in 1960-1978. After correction for the expected mortality in the general population, cumulated survival rates (with 95% confidence limits) of 66 (58.7-72.5)% and 52 (42.0 62.1)% at 5 and 10 years respectively were found. These figures and the general pattern of relative survival rates were in close accordance with those noted in a concomitant series of female breast cancer. There was a trend toward slightly improved survival rates during the period of study and the median survival times were 3.9, 4.8 and 7.2 years for patients diagnosed in 1960-64, 1965-69 and 1970 74 respectively. Age at diagnosis was seemingly unrelated to the long-term relative survival. We conclude that, except for a slightly higher mean age at diagnosis in males, there is a striking similarity in the natural history of breast cancer between men and women after initial treatment, with an excess death rate which still persists at long-term observation. PMID- 4015957 TI - Fall in vital capacity with posture. AB - In a study of 147 subjects (50 normals, 50 with obstructive, and 47 with restrictive lung function), the mean reduction in forced vital capacity from standing to supine (delta FVC) was 7.5% (SD +/- 5.7), 11.2% (+/- 13.4), and 8.2% (+/- 7.7) respectively, with no significant difference between groups. The respective 95% upper confidence limits were 19%, 38% and 24%. We conclude that delta FVC greater than 25% associated with normal or restrictive lung function or greater than 35% associated with airways obstruction should be an indication for further study of diaphragm function. PMID- 4015958 TI - Sarcoidosis in India. AB - Sarcoidosis in India frequently presents in elderly males with a dissociation between extensive radiological changes and scanty clinical signs in the chest. Clubbing is not infrequent. Erythema nodosum, generalized lymphadenopathy, eye changes, and bone cysts are uncommon. Spontaneous resolution or asymptomatic course is very rare. Follow-up reports, whenever available, show that patients have frequent relapses which respond well to short courses of steroids. This comparative study shows a few differences between this series (of 90 cases diagnosed from 1957 to 1982), two different Western series and the World series. Detection and documentation of cases of sarcoidosis in India have been on the increase during the last few decades. Whether that is due to increase in incidence or awareness is difficult to say. In two special centres in India, the frequency of detection of the disorder varied between 61.2 (in a chest hospital in Delhi during 1957-74) to over 150 per 100 000 patients (Calcutta) attending a general hospital with a sarcoidosis clinic (1980-82). PMID- 4015959 TI - Invasive pulmonary haemangiomatosis. AB - Invasive pulmonary haemangiomatosis is a recently described disease in which exceedingly thin-walled vessels of capillary or venous dimensions infiltrate the lung parenchyma and pulmonary blood vessels. The angiomatous vessels, of obscure origin, infiltrate the media and intima of muscular pulmonary arteries, pulmonary veins and venules. The occlusion of the veins and venules by the thin-walled vessels, and the reactive intimal fibrosis they provoke, leads to pulmonary capillary dilatation, collections of intra-alveolar siderophages, fibrosis of alveolar walls and osseous nodules. This secondary pulmonary veno-occlusive disease in turn leads to hypertensive pulmonary vascular disease. Hence invasive pulmonary haemangiomatosis represents a fourth cause of 'unexplained pulmonary hypertension', the other three being unexplained plexogenic pulmonary arteriopathy, recurrent pulmonary thromboembolism, and pulmonary veno-occlusive disease. Two previously reported cases of invasive pulmonary haemangiomatosis presented with recurrent haemoptysis and the gradual development of chronic respiratory insufficiency associated with diffuse infiltrates in the chest radiograph. In one of these cases a haemothorax had developed. Such clinical features may be of importance in coming to the correct diagnosis. PMID- 4015960 TI - The twin situation and its effects on syntax and interactional language over time. PMID- 4015961 TI - The 1984 Jansson memorial lecture. Evidence upon which to act: the identification of communication disorders. PMID- 4015962 TI - Communicative activities of dysphasic adults: a survey. PMID- 4015963 TI - The effectiveness of conductive education principles with profoundly retarded multiply handicapped children. PMID- 4015964 TI - Phonetic features and phonological features in speech assessment. PMID- 4015965 TI - Mispronunciations and compensatory movements of tongue-operated patients. PMID- 4015966 TI - Evidence of genetic factors in hidradenitis suppurativa. AB - Twenty-six probands suffering from hidradenitis suppurativa were identified from Hospital Activity Analysis (H.A.A.) records for the period 1980-83 and by direct referral from hospital specialists over a 6-month period in 1983-84. Investigation of their families eventually confirmed a total of 62 affected individuals from 23 families. In II families there was evidence in favour of single gene or Mendelian inheritance; in another three there was familial occurrence; in nine families there was a negative family history at the time of enquiry. The disease appears to be commoner than reports suggest and it is probable that there is an underestimation of affected individuals in our community. Problems of identification including variable age of onset and psycho social factors were found and may be responsible for false-negative family histories. PMID- 4015967 TI - Mechanism of anthralin inflammation. I. Dissociation of response to clobetasol and indomethacin. AB - The effect of topical clobetasol propionate and a 1% topical indomethacin gel which could inhibit UV erythema was measured on anthralin inflammation by change in skin-fold thickness and erythema. The time course of the inflammatory oedema and erythema were different, as was their response to the drugs studied. The oedema of anthralin inflammation was completely inhibited by clobetasol propionate but the erythemal response showed a small and non-significant reduction. Indomethacin had no effect on anthralin oedema but produced a small but significant reduction in erythema in the first 24 h after anthralin application. These results suggest that either anthralin inflammation is not due to production of prostenoids, or that if it is, it occurs by other than the classical enzymic pathway. PMID- 4015969 TI - Neutrophilic urticaria. AB - We studied 241 consecutive skin biopsies from patients with urticaria. Ten of the 241 specimens showed inflammation of dermal venules primarily with polymorphonuclear leukocytes, without evidence of necrotizing vasculitis. We speculated that this finding might represent an early histological form of urticarial vasculitis. However, review of the clinical histories and laboratory data from these 10 cases showed that most were associated with dermographism, normocomplementaemia, and negative direct immunofluorescence. These findings suggest that urticarial lesions with the histological picture of neutrophils in vessel walls may imply the presence of physical urticaria. PMID- 4015968 TI - Mechanism of anthralin inflammation. 2. Effect of pretreatment with glucocorticoids, anthralin and removal of stratum corneum. AB - The inflammatory dose-response to anthralin was measured in human skin 24 h after pretreatment with topical corticosteroids and anthralin, and 48 h after removal of the stratum corneum with adhesive tape. Anthralin inflammation was increased after 1% hydrocortisone application and decreased by 0.1% betamethasone valerate and 0.05% clobetasol propionate; although the difference between these effects was not significant, the difference between the effect of hydrocortisone and clobetasol propionate was. Anthralin inflammation was not significantly affected by pretreatment with anthralin and was reduced, although not significantly by removal of the stratum corneum. The finding that anthralin inflammation is not altered in skin in which aryl hydrocarbon hydroxylase (AHH) activity is increased and that anthralin inflammation may be altered in situations in which AHH activity is unchanged, excludes a direct relationship between anthralin inflammation and AHH activity. PMID- 4015970 TI - The anatomy and pathogenesis of wrinkles. AB - The anatomy of linear wrinkles ("crow's feet' and temporal frown lines), fine criss-cross wrinkles of the face and wrinkling of the general body surface of elderly persons, was studied by light and scanning electron microscopy. No histological features distinguished the various wrinkles from surrounding skin. It was concluded that the wrinkle is a configuration change, like the grooves worn into an old glove, without specific structural alterations at the histological level. As regards pathogenesis, the common setting was found to be deterioration of the elastic tissue network. The skin becomes looser, excessive, and loses the ability to snap back to its original state after being deformed. PMID- 4015971 TI - The erythemal response of human skin to ultraviolet radiation. AB - A reflectance instrument was used to measure objectively the erythemal response of human skin to ultraviolet radiation. Dose-response curves have been constructed for four radiation wavelengths. In each case, the measured increase in erythema was found to be linearly related to the logarithm of the dose of ultraviolet radiation. Significantly different slopes of response were obtained for radiation of 254 and 280 nm compared with 300 and 313 nm radiation. The relevance of these findings is discussed with relation to the mechanism of erythema production and the erythema action spectrum. PMID- 4015972 TI - Acute palmoplantar pustulosis. AB - This paper describes five cases of an uncommon acral rash, acute palmoplantar pustulosis, which is precipitated by infection, and may represent a true pustular bacteria. Acute and chronic palmoplantar pustulosis are probably different forms of the same disease, but the prognosis in the acute form is good and aggressive therapy is not indicated. The relationship to psoriasis is discussed. PMID- 4015973 TI - The hair cycle on the human thigh and upper arm. AB - Hair follicle density, and definitive length, root status and rate of growth of hairs were determined for defined areas of the thigh and upper arm in 11 females and nine males aged 20-30 years. Hair follicle density did not differ between males and females. However, on the thigh the definitive length of hair was on average three times greater in males. This was attributable mainly to a longer duration of anagen (X 2 X 46), but also to a greater rate of growth (X 1 X 22). On the upper arm the hair was only 1 X 42 times longer and the duration of anagen only 1 X 27 times greater in males than in females. On the thigh the estimated average duration of anagen was 54 days in males and 22 days in females, with corresponding figures of 151 days and 84 days for the complete cycles. On the upper arms the duration of anagen was 28 days in males and 22 days in females, with corresponding figures of 108 and 106 days for the complete cycle. In females, oral contraceptives had no significant effects on any measurement. PMID- 4015974 TI - Further evidence of the safety of tar in the management of psoriasis. AB - Current concern over the carcinogenic potential of cytotoxic drugs and photochemotherapy used in the management of psoriasis increases the need for an accurate assessment of the 'background' incidence of carcinoma in psoriatics not receiving these modalities. This study compares the observed incidence of carcinoma in 719 tar-treated psoriatics with that expected, based on data from the West of Scotland Cancer Registry. No increase in malignancy was found in psoriasis over that expected in the general population. PMID- 4015975 TI - The polymorphonuclear neutrophils migrant across the human skin express mostly a Fc receptor. PMID- 4015976 TI - Neutrophil migration through denuded skin areas: a non-invasive, quantitative and reproducible method to study epidermal cicatrization in vivo in man. PMID- 4015977 TI - An in vitro lymphocytotoxicity assay for studying adverse reactions to sulphonamides. PMID- 4015978 TI - Inflammatory cell accumulation in response to intracutaneous Paf-acether: a mediator of acute and persistent inflammation? AB - The ether-linked phospholipid, Paf-acether (AGEPC) is released from a variety of inflammatory cell types and has properties consistent with those of a mediator of inflammation. We have examined the effects of locally administered Paf-acether on cellular accumulation in the skin of experimental animals and man by histological evaluation of sequential skin biopsies and quantification of accumulation of radiolabelled blood elements. In guinea-pig skin, immediate extravasation of plasma protein and intravascular accumulation of platelets and neutrophils was succeeded by a persistent mixed cellular infiltrate predominantly of neutrophils but also containing lymphocytes and histiocytes. Radiolabelling studies were consistent with these observations. Intradermal Paf-acether elicited persistent clinical and histopathological responses in human skin. The finding that Paf acether is able to initiate cutaneous cellular accumulation may be important in the pathogenesis of inflammatory dermatoses. PMID- 4015979 TI - Effect of ultraviolet irradiation on granulocyte chemotaxis and nitroblue tetrazolium reduction activity in healthy individuals. PMID- 4015980 TI - The effect of BW 540C, a novel anti-inflammatory agent, on ultraviolet-induced physical and histological changes in guinea-pig skin. AB - We have examined the effects of various topical formulations of BW 540C, a novel dual inhibitor of the cyclo-oxygenase and lipoxygenase pathways of arachidonic acid metabolism, utilizing the model of ultraviolet irradiation of guinea-pig ears. During a series of studies, BW 540C preparations were compared with a range of corticosteroids, a cyclo-oxygenase inhibitor and a placebo using both subjective and objective measurements. Results showed BW 540C base to be the best overall agent for treating the pathological changes seen in this model. PMID- 4015981 TI - The mononuclear phagocyte system in granulomas. AB - A comparison is made between immunologically induced and non-immunologically induced granulomas in guinea-pigs injected with metals (zirconium and aluminum) or with mycobacteria (BCG vaccine and Mycobacterium leprae). Immunological granulomas were characterized by epithelioid cells and fibrosis, whereas non immunological granulomas contained phagocytosing macrophages with little evidence of fibroblast activation. Epithelioid cells carry the same specific macrophage antigen as phagocytosing macrophages and this can be detected by the use of a specific monoclonal antibody. However, they differ from phagocytosing macrophages in that they are poorly phagocytic, not glass adherent and lack Ia antigen. They are however secretory cells with rough endoplasmic reticulum. A relation between the presence of these cells and increased collagen synthesis is indicated. A study of accessory cell function showed that the epithelioid cells of BCG granulomas were able to support mitogen-induced but not antigen-induced proliferation of T lymphocytes. The macrophages of M. leprae granulomas did not support either a mitogen- or antigen-induced proliferative response. PMID- 4015982 TI - In vivo and in vitro changes in cell-mediated immunity following tuberculin skin testing in humans. PMID- 4015983 TI - The role of circulating cells in skin reactions. PMID- 4015985 TI - British Association of Dermatologists sixty-fifth annual meeting, 1985, London. Abstracts. PMID- 4015984 TI - A role for Paf-acether (platelet-activating factor) in acute skin inflammation? PMID- 4015986 TI - Immunological aspects of platelet transfusions. PMID- 4015987 TI - The effect of indomethacin treatment on lymphocyte PHA reactivity in healthy controls and patients with lymphoma and sarcoidosis. AB - Lymphocytes from healthy volunteers who took indomethacin orally for 3 d showed an enhanced in vitro response to phytohaemagglutinin (PHA). When indomethacin was added in vitro, lymphocytes from healthy controls showed similar but more consistent increases of PHA responses than lymphocytes from patients with sarcoidosis or lymphoma. Moreover, the enhancing effect of indomethacin was by and large more pronounced in those patients who had relatively normal PHA lymphocyte responses in the absence of indomethacin, and the presence of indomethacin failed in most instances to increase subnormal responses to normal control levels. These findings are not consistent with the notion that increased prostaglandin synthesis is the principal cause of subnormal PHA reactivity of lymphocytes from patients with sarcoidosis or lymphoma. PMID- 4015988 TI - Marrow cell necrosis in anorexia nervosa and involuntary starvation. AB - Marrow specimens from six patients with anorexia nervosa and three with involuntary starvation were examined for the presence of gelatinous transformation and marrow cell necrosis. Five of the patients had pancytopenia. Acanthocytes were present in the circulation of all nine. In only two patients was marrow cellularity adequate. Gelatinous transformation was present in every marrow specimen and was of a marked degree in eight. Marrow cell necrosis was identified in all nine marrow specimens. The necrosis was extensive in one specimen, focal in the others and limited to the areas of gelatinous transformation. Severe malnutrition was the single element common to all the patients. PMID- 4015989 TI - Effects of cetiedil on the oxidative metabolism of activated polymorphonuclear leucocytes. AB - Cetiedil, alpha-cyclohexyl-3-thiopheneacetic acid 2-(hexahydro-lH-azepin-l-yl) ethyl ester, was found to specifically suppress oxygen uptake by polymorphonuclear leucocytes (PMN) that were exposed to myristate or heat-killed E. coli. The chemical had no effect on the basal respiration rate of PMN in the resting state. Inhibition of oxygen uptake by cetiedil was proportionate to the degree of inhibition of the generation of O-2 and H2O2. It was also found that cetiedil suppressed the rate of the phagocytosis by PMN of opsonized oil droplets. Cetiedil had no effect on subcellular NADPH oxidase, an enzyme responsible for the respiratory burst that is activated by the perturbation of PMN plasma membrane with phagocytable particles or stimulators such as myristate. These results suggest that cetiedil affects the trigger mechanism of the plasma membrane to inhibit the activation of NADPH oxidase. PMID- 4015990 TI - Unclassified type of congenital dyserythropoietic anaemia (CDA) with prominent peripheral erythroblastosis. AB - Two unrelated cases of congenital dyserythropoietic anaemia (CDA) are described. They show striking similarities which could not be attributed to one of the well known types of CDA or any other congenital disease of the erythroid system. Both patients were followed for many years before and after splenectomy. There was a long-lasting, prominent post-splenectomy erythroblastosis, suggesting impairment of red cell denucleation. The type of heredity is unknown, and the enzymatic or molecular basis of the changes observed is not understood. PMID- 4015991 TI - Studies on the locomotory behaviour and adhesive properties of mononuclear phagocytes from blood. AB - Mononuclear phagocytes isolated from peripheral blood move slowly on albumin-, collagen- and fibronectin-coated glass, as judged by analysis of time-lapse film, although their movement is stimulated somewhat by serum. When a differential adhesion method is used to purify monocytes from a crude mononuclear cell fraction it appears to select a particularly slow-moving sub-group. Despite their slow rate of movement (especially in comparison with neutrophils) monocytes move over and penetrate monolayers of endothelial cells, apparently without difficulty; they are, however, restricted to the upper surface of a fibroblast monolayer. Penetration of reconstituted collagen gels by freshly isolated monocytes was not observed but cultured monocytes, which spontaneously detached from the culture substratum over a 48 h period, did invade collagen gels. The adhesive properties of these cultured cells, measured in a flow-chamber assay, did not differ from freshly isolated monocytes purified on serum-coated dishes and detached with EDTA, and their invasive capacity does not seem to be a consequence of altered adhesive properties. The behavioural differences between monocytes and neutrophils are considerable, although both cell types have to leave the circulation and penetrate tissues in vivo. PMID- 4015992 TI - Plasma fibronectin in idiopathic myelofibrosis. PMID- 4015993 TI - Incidence of Hb C trait in an area of southern Spain. PMID- 4015994 TI - Nasal cancer in the textile and clothing industries. AB - A case-control study of 160 patients with cancers of the nasal cavity and paranasal sinuses and 290 controls showed an excess risk associated with employment in the textile or clothing industries, with the increase (relative risk [RR] = 2.1) found only among female workers. There was, however, no increasing trend in risk with years of employment or duration since first exposure. Both male and female workers were at an increased risk of adenocarcinoma (RR = 2.5), with further enhancement of risks for those experiencing dusty work conditions. Although aetiological inferences cannot be drawn from this study, the finding of raised risk supports some previous observations and the need for further investigation of the cancer experienced by textile and clothing workers. PMID- 4015995 TI - Raised mortality from lung cancer and high sex ratios of births associated with industrial pollution. AB - Geographical and temporal associations were shown between high mortality from lung cancer and a high sex ratio of births both in the town of Bathgate (Scotland) and in the area of that town which was most exposed to polluted air from a local steel foundry. These findings constituted a replication of a similar association in an adjacent town. PMID- 4015996 TI - Mutagenicity studies in a tyre plant: in vitro activity of workers' urinary concentrates and raw materials. AB - The possible contribution to urinary mutagenicity of occupational exposures in the rubber industry was studied by assaying the urine concentrates of 72 workmen (44 smokers) employed in a tyre plant. Twenty three clerks (16 smokers) engaged in the administrative department of the same factory served as presumptive unexposed controls. XAD-2 resin concentrates of urine samples were assayed in the plate incorporation test and in the microtitre fluctuation assay with Salmonella typhimurium strains TA1535, TA98, and TA100. Furthermore, the in vitro mutagenicity of the major raw materials in use at the plant was determined in the plate incorporation assay with S typhimurium strains TA1535, TA1537, TA98, and TA100. The results obtained from the urinary mutagenicity study show that smoking habits, but not occupation, were statistically significantly related to the appearance of a urinary mutagenicity that was detectable with strain TA98. A possible synergistic effect of occupation with smoking was observed among tyre builders who were also smokers. The study of the raw materials showed that three technical grade materials were weakly active as mutagens in strain TA98 in the absence (poly-p-dinitrosobenzene) or in the presence of metabolic activation (mixed diaryl-p-phenylendiamines and tetramethyltiuram disulphide). The latter chemical was also weakly active in strain TA100. PMID- 4015997 TI - Female reproductive health in two lamp factories: effects of exposure to inorganic mercury vapour and stress factors. AB - To evaluate the possible influence of mercury vapour on female reproduction, 153 women working in a mercury vapour lamp factory have been compared with 193 women employed in another factory of the same company, where mercury was not used. Both groups of subjects were exposed to stress factors (noise, rhythms of production, and shift work). The production process has been analysed by inspection of the plants and by collective discussions with "homogeneous groups" of workers; a retrospective inquiry into work history and reproductive health events has been subsequently performed by an individual interview. Women exposed to mercury vapour currently not exceeding the time weighted average air concentration of 0.01 mg/m3 declared higher prevalence and incidence rates of menstrual disorders, primary subfecundity, and adverse pregnancy outcome; however, the progression of these problems with the level of exposure to mercury inside the same factory was not always clear. The results of this study neither prove nor exclude the possibility that occupational exposure to this concentration of mercury has a negative effect on female reproduction. PMID- 4015998 TI - Respiratory impairment in coffee factory workers in the Asaro Valley of Papua New Guinea. AB - In a coffee growing area of Papua New Guinea, a developing country in the western Pacific region, coffee factory workers were found to have more chronic symptomatic respiratory impairment than a carefully matched group of neighbouring villagers. This impairment was not related to their duration of employment. Coffee factory workers were found also to have a greater prevalence of reversible but asymptomatic airways obstruction on entering their factories after two days off duty than a group of soft drink factory workers. These findings are thought to be related to exposure to the dust produced in large quantities during coffee processing. PMID- 4015999 TI - Byssinosis in Hong Kong. AB - After a report in 1980 of the first three diagnosed locally cases and a preliminary epidemiological investigation that found little evidence of the disease, a survey was aimed at determining the prevalence of byssinosis in Hong Kong. Some 1776 workers in six cotton mills were studied using the standard MRC questionnaire and portable spirometers. Only 48 (2.7%) of the mill workers had symptoms acceptable for a diagnosis of byssinosis. The pattern of relation to dust exposure levels was similar to findings in other countries: blowing and carding process operatives had twice the prevalence rate of the spinners. Another 178 workers (10%) had symptoms of chest tightness or breathlessness or both that were not related to the first exposure after a break and therefore did not fit the standard diagnosis. Some 257 workers (14.5%) had chronic obstructive airflow disease but only 12 (4.7%) had chronic bronchitis. Job mobility had self selection of sensitive cases out of cotton dust exposure seem the most likely explanations for the low prevalence. The significance of non-specific lung ailments needs further assessment to elucidate the possible connection with cotton dust exposure. PMID- 4016000 TI - Neurophysiological studies on workers exposed to lead. PMID- 4016001 TI - Health problems of pesticide usage in the Third World. PMID- 4016002 TI - Occupational lead neurotoxicity: improvement in behavioural effects after reduction of exposure. AB - To evaluate critical exposure levels and the reversibility of lead neurotoxicity a group of lead exposed foundry workers and an unexposed reference population were followed up for three years. During this period, tests designed to monitor neurobehavioural function and lead dose were administered. Evaluations of 160 workers during the first year showed dose dependent decrements in mood, visual/motor performance, memory, and verbal concept formation. Subsequently, an improvement in the hygienic conditions at the plant resulted in striking reductions in blood lead concentrations over the following two years. Attendant improvement in indices of tension (20% reduction), anger (18%), depression (26%), fatigue (27%), and confusion (13%) was observed. Performance on neurobehavioural testing generally correlated best with integrated dose estimates derived from blood lead concentrations measured periodically over the study period; zinc protoporphyrin levels were less well correlated with function. This investigation confirms the importance of compliance with workplace standards designed to lower exposures to ensure that individual blood lead concentrations remain below 50 micrograms/dl. PMID- 4016003 TI - Radiation, work experience, and cause specific mortality among workers at an energy research laboratory. AB - A retrospective cohort mortality study was conducted among 8375 white male employees who had worked at the Oak Ridge National Laboratory for at least one month between 1943 and 1972. This plant has been the site of energy related research, including uranium and plutonium reactor technology and radioisotope production. Radiation doses, primarily from gamma rays, were generally low; the median cumulative exposure for workers was 0.16 rems. Historical follow up was conducted for the years 1943-77 and ascertainment of vital status was achieved for 92.3% of the cohort. Standardised mortality ratios (SMRs) were computed to contrast the subjects' cause specific mortality experience with that of the United States white male population. The observed number of 966 deaths from all causes was 73% of the number expected. Mortality deficits were also seen for arteriosclerotic heart disease (SMR = 0.75; 344 observed) and all cancers (SMR = 0.78; 194 observed). These results are indicative of the healthy worker effect and the favourable influence on health of the cohort's relatively high socioeconomic status. Non-statistically significant raised SMRs were seen for all leukaemias (SMR = 1.49, 16 observed), cancer of the prostate (SMR = 1.16, 14 observed), and Hodgkin's disease (SMR = 1.10, 5 observed). Internal comparisons of mortality (standardised rate ratios, SRRs) were made between subgroups of the cohort according to radiation dose level and duration of employment in various job categories. No consistent gradients of cause specific mortality were detected for radiation exposure. Leukaemia mortality was highest among workers with greater than or equal to 10 years employment in engineering (SRR = 2.40) and maintenance (SRR = 3.12) jobs. The association of leukaemia with employment in engineering was unexpected; maintenance jobs entail potential exposures to radiation and to a wide range of organic chemicals; metals, and other substances. PMID- 4016004 TI - Minor psychiatric morbidity and labour turnover. AB - The relation of minor psychiatric morbidity with labour turnover is examined, using data from a study of young, predominantly middle class, white collar men and women. The results suggest that the presence of psychiatric symptomatology is at least as important as occupational attitudes in identifying individuals who would subsequently leave the organisation. PMID- 4016005 TI - Prostatic cancer and chronic respiratory and renal disease in British cadmium workers: a case control study. AB - Deaths due to prostatic cancer, renal cancer, bronchitis or emphysema, and nephritis or nephrosis in three cohorts of cadmium workers have been investigated in a case-control study. Evidence of an association of risk for these diseases with intensity and duration of exposure to cadmium was sought. The only clearly statistically significant finding was of an association of deaths coded as bronchitis or emphysema with "high" levels of exposure to cadmium fume, which was related also to duration of exposure. There was suggestive evidence also (p congruent to 0.10) of an increased risk for nephritis or nephrosis after high exposure. Marginally increased risks were observed for prostatic cancer after high or "medium" exposure, but these were not statistically significant. PMID- 4016006 TI - Cancer incidence and cancer mortality in a cohort of semiconductor workers. AB - The cancer mortality experienced by a cohort of 1807 workers from a semiconductor factory during the period 1970-82 has been investigated (as has cancer morbidity for 1970-81). Expectations for mortality were calculated on the basis of rates of mortality for the general population of England and Wales. Expectations for cancer incidence were calculated on the basis of incidence rates for the West Midland Region. For the total study cohort, observed numbers of deaths and incident cases for all cancers were close to expectation. For melanoma incidence, an observed of 3 cases was compared with an expectation of 0.68. PMID- 4016007 TI - Microanalyses of lesions and lymph nodes from coalminers' lungs. AB - The dust content and composition of lesions and hilar lymph nodes from the lungs of British coalworkers have been examined. Samples of macules, fibrotic nodules, and massive fibrosis (both peripheral and central sites) were dissected from 49 lungs. The highest mean dust concentrations (about 20%) were found in nodules and massive fibrosis. Overall there were no significant differences between the selected lesion types and their respective whole lung dust composition, although the central sites of massive fibrosis were found to contain on average a higher proportion of coal and a lower proportion of ash and its measured constituents, quartz and kaolin plus mica, than the edge of the lesion (p less than 0.001 for each component). There were striking differences between recovered lung and lymph node dusts. An examination of 180 specimens showed a mean quartz in lymph node dust of 20.3% compared with 6.1% in lung dust. As expected the proportion of quartz was greater in lymph nodes and lungs from men who had worked "low" rank (high ash) coal. By contrast with the corresponding figures for lung dusts, however, the mean proportion of quartz in nodes did not increase over the pathological range of pneumoconiotic lung disease. On average the proportions of kaolin and mica in lymph nodes reflect those found in lungs. The lymphotrophic nature of quartz was clearly shown although it was not possible to show an association between this clearance pathway and any particular type of lesion. PMID- 4016009 TI - Accuracy of occupational histories obtained from wives. PMID- 4016008 TI - Modified nucleosides in asbestos workers at high risk of malignant disease: results of a preliminary study applying discriminant analysis. AB - Patients with asbestos related malignant mesothelioma excrete high levels of modified nucleosides in their urine. The purpose of the present report was to explore further the usefulness of measuring these breakdown products of transfer RNA (tRNA) in male asbestos insulation workers who are at high neoplastic risk but without clinical signs of malignancy. Modified nucleoside levels (psi, m'A, m'I, m2G, and ac4C) were used as discriminator variables in a computer generated discriminant function in which 96% of the controls and 95% of the insulation workers were correctly classified. It was also found, using a similar multiple regression model, that 10 of 13 were correctly classified as having normal chest radiographs and 27 of 30 asbestos exposed subjects as exhibiting alterations in either the parenchyma, pleura, or both. The results suggest that measuring modified nucleosides levels in the urine of asbestos exposed workers, and perhaps others exposed to carcinogenic agents, has the potential for identifying, through multivariate statistical techniques, individuals who are at high neoplastic risk. PMID- 4016010 TI - Is low intensity vibration harmful to the digits? PMID- 4016011 TI - Do amines induce occupational asthma in workers manufacturing polyurethane foams? PMID- 4016012 TI - Mesothelioma and asbestos fibre type. PMID- 4016013 TI - Job related mortality risks of Hanford workers and their relation to cancer effects of measured doses of external radiation. PMID- 4016014 TI - Uptake of solvents from the lungs. PMID- 4016015 TI - Formaldehyde and the nasal mucosa. PMID- 4016016 TI - Transpersonal processes and the Oedipal phase of development. AB - This paper is an extension of previous theoretical work in which a bimodal theory of the psychology of relationships and personality function was elaborated. The two modes are, essentially, the traditional intrapsychic individual mode derived from dyadic and introspective methods of observation, and a transpersonal mode, derived in the main from family and group process observations. The role of projective identification and other so-called primitive mechanisms are explored and their defensive and adaptive role in transpersonal transactions in small and large groups examined. The implications for the theory of the mother-infant relationship, and in particular the separation-individuation phase, is reviewed and the further development of the transpersonal concept summarized. These ideas are developed in an examination of the influence of these processes on Oedipal phase conflicts in an eight-year-old boy, with illustrative case material. The conclusion is drawn that manifest Oedipal phase anxieties and conflicts are frequently, if not always, an expression of transpersonal elaboration in the family group. In these circumstances, the transpersonal processes are defensive rather than adaptive and impair the child's normative individuation and the usual repression and resolution of the Oedipal complex. Freud's study of Little Hans is re-examined from this viewpoint. The implications for therapy are noted. PMID- 4016017 TI - A personal construct study of depression. AB - Twelve out-patients with a 'definite' or 'probable' diagnosis of major depressive disorder were treated by the author using personal construct psychotherapy (Kelly, 1955). Changes in their construct systems were monitored at intervals during the course of therapy using traditional role construct repertory grids and 'multiple perception of the self' grids. The level of depression was measured on each occasion of testing using psychiatric and self-rating depression scales. The most important findings were that high levels of depression were associated with low levels of 'conflict' and a cluster of variables to do with the construing of self, namely negative self-construing, low self-esteem and perceived self isolation. As the depression lifted during the course of psychotherapy, there was a significant increase in the amount of 'conflict' and in the level of self esteem, and a significant decrease in the level of self-isolation. The fact that over time the 'multiple perception of self' grids changed significantly more than the grids concerned with the construing of the self and others is interpreted as further evidence of the crucial role that the self-concept plays in depression. PMID- 4016018 TI - Narcissism and the narcissistic personality disorder: a comparison of the theories of Kernberg and Kohut. AB - Narcissism has been a perennial topic for psychoanalytic papers since Freud's 'On narcissism: An introduction' (1914). The understanding of this field has recently been greatly furthered by the analytical writings of Kernberg and Kohut despite, or perhaps because of, their glaring disagreements. Despite such theoretical advances, clinical theory has far outpaced clinical practice. This paper provides a clarification of the characteristics, diagnosis and development of the narcissistic personality disorder and draws out the differing treatment implications, at various levels of psychological intensity, of the two theories discussed. PMID- 4016019 TI - Psychological adjustment and the facilitative nature of close personal relationships. AB - The Rogerian hypothesis that psychological adjustment is positively related to having a relationship which is perceived as being characterized by understanding, congruence and unconditional acceptance was tested in the context of a current, close relationship, using the original Relationship Inventory in two studies which used different measures of assessing psychological adjustment. In the first study 26 females and 19 males completed Phillips' questionnaire which assesses acceptance of self and of others, while in the second study, 98 females and 23 males completed Rosenberg's Self-Esteem Scale and a 30-item symptom checklist. The hypothesis was strongly confirmed for the females but not for the males in both studies. PMID- 4016020 TI - Attitudes of psychiatric nurses to treatment and patients. AB - A sample of 208 psychiatric nurses and nursing assistants completed a questionnaire assessing attitudes to treatment and patients. Significant attitudinal differences between groups were found in relation to professional grade, age and sex. Staff with more professional training were less authoritarian and impersonal than staff more junior in the hierarchy. Younger males with Registered Mental Nurse training were found to be significantly less inclined towards physical methods of nursing and treatment. Male nurses tended to favour therapeutic techniques which emphasized independent nurse action and psychological proximity to patients. Female nurses were more favourably inclined to physical methods of treatment and were significantly more authoritarian and formal towards patients in line with the traditional stereotype of the general hospital nurse. Results are discussed in relation to the setting up of new treatment regimes within psychiatric hospitals and the influence that staff attitudes have on their functioning. PMID- 4016021 TI - Younger man/older woman: a cautionary tale. AB - This is a single case study of a parallel relationship between (a) the patient and his romantic partner and (b) the patient and his therapist. While parallels such as these are not unusual in therapy and may, in fact, be universal, coincidences of age and duration facilitate the understanding of some of the competitive aspects of the patient-therapist-significant other triangle. PMID- 4016022 TI - The psychosocial impact of a progressive physical handicap and terminal illness (Duchenne muscular dystrophy) on adolescents and their families. AB - This paper reports in narrative style on a sample of 13-16-year-old Duchenne muscular dystrophy adolescents in a residential setting in the UK. The terminally ill dystrophic boys' physical handicaps were noticed at about five years of age. In-depth interviews were conducted with parents, while projective assessment and psychodrama were used with the boys. Findings for this paper draw heavily on family interviews. Not surprisingly, the Duchenne boys evinced significant isolation from the mainstream of normal culture. The parents of the terminal group showed marked preoccupation with their sons, great stress and diminished expression of enjoyment. The Duchenne adolescents raised the issue of handicap surprisingly often with their parents, suggesting their great need to acknowledge their disease with parents. Their parents, however, evinced marked difficulty in responding to death issues with the boys - a reaction which leaves the boys alone and the parents guilty. These observations on the family are discussed in the context of a family identification process. PMID- 4016023 TI - Left and right cerebral hemisphere differences in the occurrence of epilepsy. AB - Differences in function between the cerebral hemispheres are well documented for normal subjects and, in diseased states, these are used to lateralize and localize a dysfunction. However, the difference in frequency of occurrence of left vs. right hemisphere lesions and the greater likelihood of epilepsy occurring on the left have received scant attention. In the present study patients with a diagnosis of meningioma or cerebral abscess were identified from the EEG computer file. After operation the meningioma patients with predominantly left-sided tumours showed a statistically significant greater chance of developing seizures, similarly those with left-sided cerebral abscess. Considering a larger group of patients with temporal lobe epilepsy from a variety of causes, a left-sided EEG focus occurred more frequently - and was statistically significant - than a right-sided or bilateral disturbance. The full explanation of these results is not clear but they suggest that the hemispheres function differently in patients with a cerebral disorder like epilepsy, as is known to be the case in normal subjects. PMID- 4016024 TI - Anorexia nervosa in adolescents. AB - This paper is a retrospective study of 40 carefully defined cases of anorexia nervosa in adolescents. The illness in adolescence appears similar to that in older patients with regard to most clinical features, an increased referral rate since the 1960s, an upper social class predominance, and the importance of antecedent events. Bingeing and vomiting appear to be relatively rare features of anorexia nervosa in adolescents. PMID- 4016025 TI - Homozygous alpha-thalassaemia: clinical presentation, diagnosis and management. A review of 46 cases. AB - Forty-six hydropic infants with homozygous alpha-thalassaemia born during a period of 10 years have been reviewed. The incidence was 1:1550 total births, and accounted for 81% of all non-immune hydrops. The male to female ratio was 1:1.4. There was increased incidence of anaemia, pregnancy induced hypertension, antepartum haemorrhage, malpresentation, prematurity, fetal distress, difficult vaginal delivery, caesarean section, retained placenta, postpartum haemorrhage and congenital abnormalities. Antenatal diagnosis by DNA hybridization with subsequent abortion of the affected fetuses is the best method to decrease maternal morbidity and to reduce the incidence of hydrops fetalis in couples at risk. For those with no previous history, but with early onset hypertension and/or polyhydramnios, sonography is useful in making an earlier diagnosis, and in reducing avoidable morbidity, because DNA analysis can be done before caesarean section and aggressive neonatal management is instituted. PMID- 4016026 TI - Successful prenatal treatment of non-immune hydrops fetalis due to congenital chylothorax. Case report. PMID- 4016027 TI - A comparative study of methods of oxytocin administration for induction of labour. AB - Equipment has become available for the automatic infusion of oxytocin in a closed loop system for the induction of labour. This system was compared with manual administration of oxytocin by peristaltic infusion pump, the dosage being based on data derived from an intrauterine catheter or by clinical assessment of uterine activity. A total of 121 patients classified according to parity and cervical score were allocated to an automatic infusion system (AIS) or a peristaltic infusion pump system. Patient characteristics were similar in both groups. Labour was significantly longer in those induced by automatic infusion system particularly in nulliparae and patients with poor cervical scores. In 53.3% of the nulliparae with poor cervical scores the automatic infusion system proved inadequate to effect vaginal delivery. Neonatal outcome was similar in both groups. Automatic infusion of oxytocin by the present system increased the length of induced labour and had no statistically significant effect on neonatal outcome, conferring no advantage over a more traditional method of oxytocin administration. PMID- 4016028 TI - Total uterine activity in induced labour--an index of cervical and pelvic tissue resistance. AB - Uterine activity was studied during labour induced using an automatic infusion system (AIS) or a peristaltic infusion pump (IVAC) to administer oxytocin. In the 110 patients who achieved vaginal delivery the total uterine activity required to effect full dilatation of the uterine cervix was found to vary according to parity and cervical score but not according to mode of oxytocin infusion. Irrespective of whether the uterine activity level per 15 min was maintained at between 700 and 1500 kPas or at between 1500 and 2000 kPas, the total uterine activity was similar the lower levels being compensated for by a longer duration. Fetal outcome, in terms of 1- and 5-min Apgar scores and umbilical vein blood pH, was unaffected by the level of uterine activity. The cervical and pelvic tissue resistance varies according to parity and cervical score and the uterus has to achieve a certain total uterine activity in induced labour which is best achieved by maintaining optimal uterine activity levels of 1500-2000 kPas/15 min to effect vaginal delivery of the baby in good condition in optimal time. PMID- 4016029 TI - Sex steroid hormone concentrations in preterm labour and the outcome of treatment with ritodrine. AB - Peripheral plasma concentrations of unconjugated oestradiol-17 beta, progesterone and total oestriol were measured in patients presenting with uncomplicated preterm labour. Control samples were obtained from normal healthy women matched for maternal age, parity and duration of pregnancy. Oestrogen concentrations were often higher and progesterone concentrations often lower in patients presenting in preterm labour, and in particular, in those presenting in advanced labour and those failing to respond to treatment with ritodrine, but the differences were not statistically significant. PMID- 4016030 TI - Fatal pulmonary oedema associated with the use of ritodrine in pregnancy. Case report. PMID- 4016031 TI - Placental transfer of bupivacaine, pethidine and lignocaine in the rabbit. Effect of umbilical flow rate and protein content. AB - The factors determining the placental transfer of drugs used in labour were studied in the rabbit placenta perfused in situ with Krebs bicarbonate buffer. During concurrent maternal intravenous infusion of bupivacaine, lignocaine, pethidine and antipyrine, drug concentrations were measured in maternal arterial plasma and placental effluent perfusate, the flow rate and protein content of which were varied. Protein binding and content were also measured. Placental clearance of antipyrine, which is unbound, was unaltered by perfusate protein content, and increased with umbilical perfusate flow up to 2 ml/min. Clearance of lignocaine and pethidine, which were 20-30% protein bound, increased to a small extent with perfusate protein, and were flow-dependent up to the maximum perfusate flow of 4 ml/min. Clearances of bupivacaine, which was greater than 80% bound, increased markedly with perfusate protein but, though flow-dependent, was one-tenth to one-fifth that of the other drugs. Fetal binding and glycoprotein content were less than maternal, hence the equilibrium fetal: maternal ratio is predictably lower for the highly bound bupivacaine than for lignocaine or pethidine. Measured fetal: maternal ratios of bupivacaine were, however, only one half to one-third of the predicted equilibrium values, suggesting that bupivacaine does not unbind readily in a single transit through the rabbit placenta. Thus, though bupivacaine crosses the placenta more slowly than the other drugs, the fetal dose of all these drugs will be greatest in healthy babies with good placental blood flows and high plasma proteins. PMID- 4016032 TI - Quantitative structural studies on human placentas associated with pre-eclampsia, essential hypertension and intrauterine growth retardation. AB - Placentas from pregnancies complicated by pre-eclampsia, essential hypertension, hypertension complicated by pre-eclampsia and from normotensive pregnancies resulting in the birth of a singleton small-for-dates (SFD) infant have been studied by quantitative morphometry. The findings have been compared with those from placentas of uncomplicated pregnancies. The placentas from pregnancies complicated by pre-eclampsia and those resulting in a SFD baby had a significantly lower total volume, volume of parenchyma and villous surface area when compared with normal pregnancies of comparable gestation. They also had an increase in areas of multiple infarction and in the volume proportions occupied by fetal capillaries. The placentas from women with essential hypertension uncomplicated by pre-eclampsia were as large as those from normal pregnancies and the villous surface areas were as high. Villous surface area measurements in the different groups were related to gestation and to fetal weight. PMID- 4016033 TI - Sympatho-adrenal and cardiovascular reactivity in pregnancy-induced hypertension. I. Responses to isometric exercise and a cold pressor test. AB - Sympatho-adrenal and cardiovascular reactivity was studied in patients with pregnancy-induced hypertension (PIH) and healthy pregnant controls subjected to an isometric handgrip test and a cold pressor test both during and after the pregnancy. At rest, heart rate was higher in the PIH group than in the control group both during and after pregnancy. Forearm vascular resistance was not affected by PIH or by pregnancy per se. During pregnancy arterial plasma adrenaline levels were suppressed in the control group both when compared with the PIH group and postpartum values. Arterial noradrenaline levels were similar and normal in the two groups at both examinations. The isometric exercise increased systolic and diastolic blood pressures, heart rate and noradrenaline and reduced vascular resistance similarly in the PIH and control groups on both occasions. Vasoconstrictor responses to the cold pressor test were reduced during pregnancy but there were no differences between the groups on either occasion. Noradrenaline responses to the cold pressor test were not influenced by PIH or by pregnancy per se. During pregnancy adrenaline responses to the two tests tended to be reduced in the controls but not in PIH. Our results indicate enhanced adrenomedullary activity in PIH when compared with the suppressed activity in normal pregnancy. Cardiovascular reactivity to the tests was similar in the PIH and control groups. The normal arterial noradrenaline levels at rest and during provocation do not support the contention of a generalized increase in sympathetic nerve activity in PIH. PMID- 4016034 TI - Quantitation of vaginal discharge in healthy volunteers. AB - The mean quantity of vaginal discharge measured on four occasions during one menstrual cycle in 22 asymptomatic volunteers was 1.55 g/8 h although the amount varied significantly between different days of the cycle. The maximum occurred at mid-cycle (1.96 g/8 h) and low mean values were seen on day 7 (1.38 g/8 h) and day 26 (1.37 g/8 h), contrasting with the widely held view that the discharge increases premenstrually. This cyclical variation was statistically significant (P less than 0.02) in celibate women using no contraception but was less marked in sexually active women taking the combined oral contraceptive pill. PMID- 4016035 TI - The normal menstrual cycle has no effect on gastric emptying. AB - Recent studies have demonstrated that orocaecal transit time is prolonged both in the luteal phase of the ovulatory cycle in normal women and during pregnancy, but have made no attempt to differentiate between the individual effects of gastric emptying and small intestinal transit. We have assessed the effect of the normal menstrual cycle on gastric emptying of solids and liquids in 10 women, using a dual isotope scintigraphic technique. In each subject gastric emptying was measured on 2 days: first during the follicular phase (day 8-10) and then during the luteal phase (day 18-20) of one ovulatory menstrual cycle (where day 1 was the first day of menstrual bleeding). Measures of solid and liquid gastric emptying did not change significantly between the follicular and luteal phases indicating that the normal menstrual cycle has no effect on gastric emptying. PMID- 4016036 TI - The management of cervical intraepithelial neoplasia by coagulation electrodiathermy. AB - Of 140 women with cervical intraepithelial neoplasia treated with a single application of coagulation electrodiathermy, 123 (88%) remain cytologically free of disease after a median follow-up of 3 years. The new squamocolumnar junction was colposcopically visible in 70% of the 130 patients assessed after treatment. In 15 of 17 women requiring further treatment, residual disease was suspected at the time of the first postoperative assessment. The incidence of significant morbidity following this procedure was 4%. In selected patients coagulation electrodiathermy is an effective method of treating pre-invasive disease of the cervix. PMID- 4016037 TI - Antenatal diagnosis of omphalocele and planned primary closure at birth. Case reports. PMID- 4016038 TI - On the nature and the role of the subsurface vesicles in the outer epithelial cells of the conjunctiva. AB - The layer of the tear film in contact with the conjunctiva is mucus. This mucus comes from two sources, the conjunctival goblet cells and the subsurface vesicles. These vesicles are found just below the surface of the conjunctival cells. They contain long chain mucus glycoprotein molecules that are joined to the vesicle membrane. The vesicles fuse with the surface membrane of the conjunctival cells and expose their mucus glycoprotein chains to the overlying mucus. Chemical and physical bonds between the two types of mucus help to bind the mucus layer to the conjunctiva. The vesicle membrane becomes incorporated in the cell membrane and supplies the membranes for the microvilli that cover the exposed surface. PMID- 4016039 TI - Indications for vitrectomy in congenital retinoschisis. AB - Two patients with congenital retinoschisis developed rhegmatogenous retinal detachments with either a tractional component or associated vitreous haemorrhage. The second patient also had a large, raised schisis cavity under vitreous traction, which obscured visualisation of the macula. Vitrectomy is indicated for some patients with congenital retinoschisis. PMID- 4016040 TI - Extracapsular lens extraction and posterior chamber intraocular lens insertion combined with trabeculectomy. AB - Trabeculectomy for primary glaucoma was successfully combined with extracapsular lens extraction and insertion of a Pearce tripod posterior chamber lens in seven eyes of five patients. The results were similar to those expected from each component of the operation when performed alone, and all eyes achieved visual acuity of 6/9 or better with control of intraocular pressure below 22 mmHg without supplementary medical treatment. The incidence of mild anterior uveitis (three out of seven eyes) and hyphaema (two out of seven eyes) was greater than usual with this type of cataract extraction but no more than expected after trabeculectomy. Mydriatic drops may be used to treat postoperative iritis without danger to the stability of this pattern of implant. In addition the anterior chamber cannot become shallow, as the rigid legs of this lens extend behind the iris beyond the periphery of the cornea and prevent forward movement of the implant even if there is excessively free drainage of aqueous after the operation. PMID- 4016041 TI - Assessment of bleeding in eye surgery. AB - A new method for assessing microhaemorrhage in eye surgery was used in 16 patients for cataract extraction. It was shown that bleeding was greatest in the first five minutes and that it correlated with the surgeon's clinical estimate of blood loss. The method was used to assess the effect of two different general anaesthetic induction regimens on intraoperative bleeding. PMID- 4016042 TI - Medical conditions underlying recurrence of retinal vein occlusion. AB - Seventeen patients with recurrent retinal vein occlusion were investigated for underlying medical conditions and compared with 61 patients with single retinal vein occlusion (26 with central, 35 with branch vein occlusion). The two study groups were comparable for age, sex, and weight. Patients with recurrence had a significantly increased prevalence rate of hypertension (88% versus 48%: p less than 0.01), with a trend to increased hyperlipidaemia (47% versus 33%) compared with patients with a single episode. A significantly raised mean systolic (p less than 0.05) but not diastolic blood pressure was found in patients with recurrence. Other cardiovascular risk factors in patients with recurrence were also found and included lower mean levels of high density lipoprotein (HDL) cholesterol (p less than 0.02) and the HDL2 subfraction (p less than 0.001), and a significantly increased proportion of patients with regular alcohol intake (p less than 0.01). We conclude that hypertension and hyperlipidaemia with an increase in other cardiovascular risk factors are commonly found in patients with recurrent retinal vein occlusion and may therefore be important aetiological factors. The possible benefits of treatment of these underlying conditions to prevent recurrence need to be assessed in well designed prospective studies. PMID- 4016043 TI - Anisometropia in children: analysis of a hospital population. AB - In a hospital population of 1356 children 64 (4.7%) cases of anisometropia (at least 2 diopters in spherical or cylindrical power) were found. After the exclusion of all children with ocular lesions 53 remained. Twenty-seven (42%) of them had strabismus, which seemed to be related to accommodation effort rather than amount of anisometropia. Amblyopia was present in 17 (53%) of the patients with orthotropic anisometropia. Amblyopia increased with the amount of anisometropia. Therapy in the form of spectacle correction and part-time occlusion was successful in 47%. The success rate was related to the age of presentation. PMID- 4016044 TI - Bilateral superior oblique palsies. AB - Eighteen consecutive cases of bilateral superior oblique palsy have been studied retrospectively. The patients were typically adults with a history of severe head trauma. All patients complained of diplopia, either vertical, torsional, or both. Other neurological sequelae were common. Central disruption of fusion was seen in three patients. Eight patients underwent surgery for torsional or vertical diplopia, and the results are briefly discussed. PMID- 4016045 TI - Ring melanoma of the iris and ciliary body. AB - The case is described of a tumour of the iris and ciliary body--a ring type melanoma--primarily diagnosed and treated as pigmentary glaucoma. PMID- 4016046 TI - Corneal sensitivity in myasthenia gravis. AB - Corneal touch thresholds were measured in 11 people suffering from myasthenia gravis (MG) and in a control group of 20 subjects. The mean threshold in MG was 75.6 mg (SD 52) and in the control group 18.9 mg (SD 7.3); thresholds were thus significantly (p less than 0.01) raised in MG. Although it is not possible to say whether the sensory deficit is due to MG or to the treatment, the results implicate acetylcholine in sensory transduction in the cornea. PMID- 4016047 TI - Fundus flavimaculatus: polymorphic retinal change in siblings. AB - A 12-year-old boy and an 11-year-old girl, siblings of healthy, consanguineous parents, had a bilateral retinal dystrophy with a gradual loss of vision. The brother showed a bull's eye macular change with sparse fundus flavimaculatus type flecks. The sister had numerous fleck lesions of fundus flavimaculatus throughout the posterior fundus, but there was virtually no macular change. Thus the siblings presented instances of polymorphic expressivity of fundus flavimaculatus. PMID- 4016048 TI - Destructive epidemic Neisseria gonorrheae keratoconjunctivitis in African adults. AB - An epidemic of Neisseria gonorrheae keratoconjunctivitis in African adults occurred in Malawi in 1983. Sixteen patients, seven females and nine males, aged 18 to 60 years, were admitted to the inpatient ocular services at Queen Elizabeth Central Hospital in Blantyre from 1 February to 28 May 1983, all with severe bilateral purulent keratoconjunctivitis and concomitant venereal infection secondary to N. gonorrheae. Corneal melting, corneal perforation with iris prolapse, and endophthalmitis occurred in 10 eyes, of which five required enucleation. Thirteen additional eyes sustained severe visual loss secondary to corneal ulceration, leucomata, and healed corneal perforation. The route of transmission and factors of epidemicity are speculative. Because of worldwide epidemic venereal infection ophthalmologists and epidemiologists should be alert to probable sporadic N. gonorrheae epidemics in adults. Such outbreaks could occur elsewhere, especially in the developing world, and ocular gonococcal infection might become a significant cause of irreversible blindness. PMID- 4016049 TI - Effect of intravitreal hyaluronidase on the clearance of tritiated water from the vitreous to the choroid. AB - The rate of transfer of intravitreally injected tritiated water from the mid vitreous to the choroid is significantly increased after depolymerization of vitreous hyaluronic acid by injected hyaluronidase. The significance of this finding is discussed in relation to such conditions as retinal detachment and reattachment. PMID- 4016050 TI - Type IV melanosomes of the human albino iris. AB - Electron microscopy of an iris biopsy specimen from a clinically tyrosinase negative human albino demonstrated type IV mature melanosomes. Possible mechanisms for the formation in this condition of these organelles, which have not previously been described at this site, are discussed. PMID- 4016051 TI - Progressive hemifacial atrophy: a case report. AB - A case of a 28-year-old Caucasian female with progressive hemifacial atrophy and atrophy of the rhomboid muscles on the ipsilateral side is reported. The literature on this condition and its treatment is reviewed. PMID- 4016052 TI - Sarcoidosis with infiltration of the external ocular muscles. PMID- 4016053 TI - Corneal thickness changes following cataract surgery: effect of lens implantation and sodium hyaluronate. AB - Consecutive patients undergoing intracapsular cataract surgery with and without lens implantation were included in one of three groups of fifteen patients for postoperative corneal thickness measurement. One group underwent cataract extraction alone, another group had cataract extraction and lens implantation using iris supported posterior chamber implants, and another group underwent lens implantation with the use of sodium hyaluronate to reform the anterior chamber after cataract extraction. Maximal increase in corneal thickness occurred within the first 24 hours of surgery in all groups. No significant difference in corneal thickness between the implant and non-implant group was found at any time. When sodium hyaluronate was used to reform the anterior chamber prior to lens implantation the increase in corneal thickness was significantly less than in the group not on sodium hyaluronate (0.01 less than p less than 0.02 on the third postoperative day). In the long term all patients' corneas returned to preoperative levels within 28 days of surgery. PMID- 4016054 TI - Hyaluronate increases intraocular pressure when used in cataract extraction. AB - A prospective randomised study of 26 eyes (24 patients) following uncomplicated intracapsular cataract surgery was carried out with three groups in which different agents were used to re-form the anterior chamber: air, seven eyes; sodium hyaluronate, seven eyes; and a combination of hyaluronate plus systemic acetazolamide, 12 eyes. The intraocular pressure (IOP) was measured by Goldmann applanation tonometry 16 hours before surgery and every eight hours after surgery for 72 hours. The IOP doubled in the two hyaluronate-treated groups for the first day following cataract surgery. By contrast, the IOP in the group receiving air initially decreased slightly. Throughout the study the effect of using acetazolamide was never statistically significant. After the first day and a half the differences in IOP among the three treatment groups disappeared, and the pressures returned to their preoperative values. PMID- 4016055 TI - Postural response of intraocular pressure following traumatic hyphaema. AB - Twenty patients with previous unilateral traumatic hyphaema and 25 age-matched controls were studied. There was a progressive rise in intraocular pressure when the patient changed from the standing to the sitting position and then to the lying position in both groups. No control eye showed a rise greater than 2 mmHg when the subject changed from sitting to lying. However, 14 (70%) of the injured eyes and 12 (60%) of the fellow eyes showed an exaggerated response. We suggest that the presence of an abnormal postural response may indicate a predisposition to post-traumatic glaucoma. Our findings are compatible with a linked control of postural intraocular pressure response between the two eyes. PMID- 4016056 TI - Q fever as a possible cause of bilateral optic neuritis. AB - A 59-year-old farmer developed a bilateral optic neuritis in the course of an infection with Coxiella burnetii (Q fever), resulting in a lasting unilateral blindness. A complete medical (including neurological) evaluation gave no evidence of other possible causes. A possible source of infection was cattle. PMID- 4016057 TI - Retinal detachment with proliferative vitreoretinopathy: surgical results with scleral buckling, closed vitrectomy, and intravitreous air injection. AB - Seventy-five cases of total retinal detachment complicated by the more advanced grades (grades C and D) of proliferative vitreoretinopathy were treated with scleral buckling, vitrectomy, and air-fluid exchange. The overall reattachment rate was 56%, ranging from 100% in grade C-1 to 26% in grade D-3. The postoperative visual acuity was 6/120 or better in 48% of the 42 eyes in which the retina was reattached. The major causes of surgical failure were redetachment from persistent vitreoretinal traction (32%) and intraoperative complications (12%). PMID- 4016058 TI - Hyperprolinaemia and gyrate atrophy of the choroid and retina in members of the same family. PMID- 4016059 TI - Microbial and immunological investigations of chronic non-ulcerative blepharitis and meibomianitis. AB - Concentrations of tear lysozyme, lactoferrin, ceruloplasmin, IgG, and IgA have been measured by enzyme linked immunosorbent assay (ELISA) in patients with chronic non-ulcerative blepharitis and meibomianitis at the same time as the lid and conjunctivae were cultured for bacteria and fungi by a semiquantitative method. A group of normal controls aged 20 to 80 were similarly sampled, when strains of Staphylococcus epidermidis from their eyes and the patients' eyes were biotyped according to Baird-Parker's scheme. 5% of blepharitis cases had increased numbers of Staph. aureus present on the lids, compared with only a scanty growth obtained from 5% of normals. 7% of blepharitis cases had increased numbers of Staph. epidermidis type VI (coagulase-negative, mannitol-fermenting) present compared with a scanty growth obtained from 6% of normals. Isolation rates of other types of Staph. epidermidis did not differ from those in normals; no types were associated with meibomianitis. Tear protein profiles were normal in most patients, and there was no increase in tear IgA or IgG, which is expected with chronic infection. Overall our evidence suggests that in 88% of cases these lid conditions have an inflammatory aetiology not associated with infection. Staphylococcal isolates often found in the eye usually represent a normal commensal rather than pathogenic flora. PMID- 4016060 TI - Topographic visually evoked potentials induced by stereoptic stimulus. AB - Topographic processes of brain activity during stereopsis were investigated by means of two different principles, with a real stereo target and a computer stereogram. Use of either principle produced the same tendency: an electrically negative focus started from the central region of the scalp and moved to the parietal and occipital regions. These flows of excitation were seen during a period of 90 to 170 ms. The difference between these two stimulus represented a return of the negative focus from the occipital pole to the parietal region in the real stereo target and a spread of the negative focus to the temporal region in the computer stereogram. Since monocular viewing of a real stereo target produces a similar visually evoked potentials wave form but with less intensity, the negative focus in binocular viewing may be due to the enhancement of binocular cells and disparity sensitive neurons in a wide area of the brain cortex. Thus stereoptic brain responses start from the central and parietal regions and move to the occipital region, making a flow of excitation. PMID- 4016061 TI - Progressive retinal atrophy in the Abyssinian cat: studies of the DC-recorded electroretinogram and the standing potential of the eye. AB - DC-recorded electroretinography (ERG) and direct recordings of the standing potential (SP) were performed on a group of normal cats and Abyssinian cats affected by a hereditary retinal degenerative disease with similarities to human retinitis pigmentosa. A significant reduction of a- and b-wave amplitudes was found at an early stage of disease at a time when there were no major alterations in the c-wave and SP. At later stages both the c-wave and the SP oscillations were significantly reduced or absent. These findings indicate a primary photo receptor disorder. Threshold studies for the scotopic b-wave showed a loss of retinal sensitivity early in the disease at a time when 30 Hz flicker responses were normal, which could indicate an earlier involvement of the rods than of the cones. There were no major alterations in the timing of the ERG in the affected animals tested. PMID- 4016062 TI - Bilateral nanophthalmos, pigmentary retinal dystrophy, and angle closure glaucoma -a new syndrome? AB - An unusual case of bilateral nanophthalmos with pigmentary retinal dystrophy and angle closure glaucoma is presented. This is probably the first published report of the established association of all these three entities in the same patient. The aetiological possibilities and clinical significance are discussed. PMID- 4016063 TI - Conjunctival sign in sickle cell anaemia: an in-vivo correlate of the extent of red cell heterogeneity. AB - A consecutive series of 22 stable adult inpatients with sickle cell anaemia were examined for the presence and severity of spontaneous 'comma' signs of the conjunctiva. Fifteen patients had severe conjunctival signs (more than 10 commas in the worse eye). The presence of severe conjunctival signs was associated with a broader distribution of intraerythrocytic haemoglobin concentrations (p = 0.0005). The patient group with severe conjunctival signs was not found to be significantly different from the group without such signs for age, sex, haemoglobin value, reticulocyte count, alpha-globin gene number, percentage fetal haemoglobin, or the proportion of very dense cells (CHC greater than 37 g/dl). Thus the singular heterogeneity of the erythrocytes in sickle cell disease may be indicative of the factor(s) responsible for the diagnostic comma sign. PMID- 4016064 TI - Chronic ocular ischaemia. PMID- 4016065 TI - Fluorine-19 nuclear magnetic resonance studies of lipid fatty acyl chain order and dynamics in Acholeplasma laidlawii B membranes. Gel-state disorder in the presence of methyl iso- and anteiso-branched-chain substituents. AB - The hydrocarbon chain orientational order parameters of membranes of Acholeplasma laidlawii B enriched with large quantities of a linear saturated, a methyl iso branched, or a methyl anteiso-branched fatty acid plus small quantities of various isomeric monofluoropalmitic acid probes were determined via fluorine-19 nuclear magnetic resonance spectroscopy (19F NMR) over a range of temperatures spanning the gel to liquid-crystalline phase transitions (determined by differential scanning calorimetry). Membrane orientational order profiles in the liquid-crystalline state were generally similar regardless of the particular fatty acyl structure, showing a region of relatively constant order preceding a region of progressive decline in order toward the methyl terminus of the acyl chain. In the gel state, the order profile of the linear saturated fatty acid enriched membranes was characteristically flat, with little head to tail gradation of order. In contrast, the methyl iso-branched and the methyl anteiso branched enriched membranes exhibited a local disordering in the gel phase reflected in a very pronounced head to tail gradient of order, which remained at temperatures below the lipid phase transition. In addition, the methyl iso- and anteiso-branched fatty acid enriched membranes were overall more disordered than the membrane containing only linear saturated fatty acyl groups. Thus, at a constant value of reduced temperature below the lipid phase transition, overall order decreased in the progression 15:0 greater than 16:0i greater than 16:0ai, suggesting that these methyl-branched substituents lower the lipid phase transition by disrupting the gel phase lipid chain packing.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4016066 TI - 2H NMR evidence for antibiotic-induced cholesterol immobilization in biological model membranes. AB - The interaction of the polyene antibiotic filipin with membrane sterols has been studied by deuterium nuclear magnetic resonance of the molecular probes [2,2,3,4,4,6-2H6]cholesterol and 1-myristoyl-2-[4',4',14',14',14'-2H5]myristoyl sn-glycero-3-phospho- choline. At physiological temperatures, there is evidence of filipin-induced cholesterol immobilization in the membrane. The 2H NMR spectra of cholesterol show two domains in which ordering and dynamics are very different. In one of these, cholesterol is static on the 2H NMR time scale, whereas in the other it undergoes rapid axially symmetric motions similar to those it exhibits in the drug-free membrane; this indicates that the jumping frequency of cholesterol between the labile and immobilized domains is less than 10(5) s-1. The distribution of cholesterol between these two sites is temperature dependent; at 0 degrees C all sterol molecules are immobilized, whereas at 60 degrees C they are almost totally in the labile site. In contrast to cholesterol, the phospholipids sense only one type of environment, at both the top and center of the bilayer, indicating that cholesterol acts as a screen, preventing the lipids from direct interaction with the antibiotic. At low temperature, the ordering of the lipid in the presence of cholesterol does not change upon filipin addition, whereas at elevated temperatures the local ordering of both the lipid and the labile cholesterol is significantly lower than that in the absence of the drug. Moreover, there is a very important difference between the degree of local ordering as measured by the lipids and by cholesterol at high temperatures.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4016067 TI - Thermotropic phase behavior of model membranes composed of phosphatidylcholines containing iso-branched fatty acids. 1. Differential scanning calorimetric studies. AB - The thermotropic phase behavior of aqueous dispersions of phosphatidylcholines containing one of a series of methyl iso-branched fatty acyl chains was studied by differential scanning calorimetry. These compounds exhibit a complex phase behavior on heating which includes two endothermic events, a gel/gel transition, involving a molecular packing rearrangement between two gel-state forms, and a gel/liquid-crystalline phase transition, involving the melting of the hydrocarbon chains. The gel to liquid-crystalline transition is a relatively fast, highly cooperative process which exhibits a lower transition temperature and enthalpy than do the chain-melting transitions of saturated straight-chain phosphatidylcholines of similar acyl chain length. In addition, the gel to liquid crystalline phase transition temperature is relatively insensitive to the composition of the aqueous phase. In contrast, the gel/gel transition is a slow process of lower cooperativity than the gel/liquid-crystalline phase transition and is sensitive to the composition of the bulk aqueous phase. The gel/gel transitions of the methyl iso-branched phosphatidylcholines have very different thermodynamic properties and depend in a different way on hydrocarbon chain length than do either the "subtransitions" or the "pretransitions" observed with linear saturated phosphatidylcholines. The gel/gel and gel/liquid-crystalline transitions are apparently concomitant for the shorter chain iso-branched phosphatidylcholines but diverge on the temperature scale with increasing chain length, with a pronounced odd/even alternation of the characteristic temperatures of the gel/gel transition.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4016068 TI - Thermotropic phase behavior of model membranes composed of phosphatidylcholines containing iso-branched fatty acids. 2. Infrared and 31P NMR spectroscopic studies. AB - The polymorphic phase behavior of aqueous dispersions of a number of representative phosphatidylcholines with methyl iso-branched fatty acyl chains was investigated by Fourier transform infrared (FT-IR) and phosphorus-31 nuclear magnetic resonance (31P NMR) spectroscopy. For the longer chain phosphatidylcholines, where two transitions are resolved on the temperature scale, the higher temperature event can unequivocally be assigned to the melting of the acyl chains (i.e., a gel/liquid-crystalline phase transition), whereas the lower temperature event is shown to involve a change in the packing mode of the methylene and carbonyl groups of the hydrocarbon chains in the gel state (i.e., a gel/gel transition). The infrared spectroscopic data suggest that the methyl iso branched phosphatidylcholines assume a partially dehydrated, highly ordered state at low temperatures, resembling the Lc phase recently described for the long chain n-saturated phosphatidylcholines. At higher temperatures, some branched chain phosphatidylcholines appear to assume a fully hydrated, loosely packed gel phase similar to but not identical with the P beta, phase of their linear saturated analogues. Thus, the iso-branched phosphatidylcholine gel/gel transition corresponds, at least approximately, to a summation of the structural changes accompanying both the subtransition and the pretransition characteristic of the longer chain n-saturated phosphatidylcholines. The infrared spectroscopic data also show that, in the low-temperature gel state, there are significant differences between the odd- and even-numbered isoacylphosphatidylcholines with respect to their hydrocarbon chain packing modes as well as to their head group and interfacial hydration states.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4016069 TI - Alkylation of amide linkages and cleavage of the C chain in the enzyme-activated substrate inhibition of alpha-chymotrypsin with N-nitrosamides. AB - Active-site-directed N-nitrosamides inhibit alpha-chymotrypsin through an enzyme activated-substrate mechanism. In this work, the activation results in the release--in the active site--of benzyl carbonium ions, which alkylate and inhibit the enzyme. The final ratio of benzyl groups to enzyme molecules is 1.0, but the alkyl groups are scattered over a number of sites. Reduction and alkylation of the inhibited enzyme generate peptides insoluble in most media. Guanidine hydrochloride at 6 M proved a good solvent, and its use as an eluant on G-75 Sephadex permitted separation of the peptides. In the case of 14C-labeled enzyme, such an approach has shown that all of the alkylation occurs on the C chain of the enzyme, the chain of which the active site is constructed. Chemical modification of the peptides with ethylenediamine and N-[3-(dimethylamino)propyl] N'-ethylcarbodiimide rendered them soluble in dilute acid, permitting high performance liquid chromatographic separation. Model studies have shown that the benzyl carbonium ions are highly reactive, alkylating amide linkages at both oxygen and nitrogen. Alkylation at oxygen produces imidate esters, which are labile centers. Hydrolysis of protein imidates results in a cleavage of the chain at that point, and separation of the peptides formed (followed by analysis) permits their identification. In our inhibition of alpha-chymotrypsin, a major site of O-alkylation has been identified as the carbonyl oxygen of Ser-214. Alkylation at the nitrogen atom of amide linkages generates stable labels; full hydrolysis with 6 N HC1 then leads to N-benzyl amino acids characteristic of those sites. Chromatography of this mixture and also 13C NMR spectroscopy of the intact inhibited enzyme have shown that three major N-alkylations have occurred. Tryptic digestion of the C chain of chymotrypsin, which contains all of the alkylation sites, provides evidence that the stable N sites are principally located between residue 216 and residue 230. These locations are consistent with predictions of alkylation sites based on inspection of a molecular model of chymotrypsin, with special reference to the aromatic binding pocket. PMID- 4016070 TI - Proton and phosphorus nuclear magnetic resonance studies of an oligothymidylate covalently linked to an acridine derivative and of its binding to complementary sequences. AB - An oligodeoxynucleotide containing four thymines and covalently attached to an acridine derivative through its 3'-phosphate [(Tp)4(CH2)5Acr] was synthesized. Its conformation in solution was investigated by proton magnetic resonance. Both intramolecular interactions between the acridine dye and thymines and intermolecular interactions were demonstrated. Both proton and phosphorus magnetic resonances were used to study the specific interaction of (Tp)4(CH2)5Acr with poly(rA) and (Ap)3A. The results were compared to those obtained when the acridine-containing substituent was replaced by an ethyl group attached to the 3' phosphate of the oligothymidylate. The acridine dye strongly stabilized the complexes formed with both poly(rA) and (Ap)3A. Upfield shifts of both adenine and acridine proton resonances were observed in the complexes. These results were ascribed to an intercalation of the acridine ring between A X T base pairs of the duplex structure formed by the oligothymidylate with its complementary oligoadenylate sequence. An analysis of proton and phosphorus chemical shifts as well as measurements of T1 relaxation times at different temperatures allowed us to propose several structures for the complexes formed by (Tp)4(CH2)5Acr with its complementary sequence. PMID- 4016071 TI - In vitro chloroplast protein synthesis by the chromophytic alga Olisthodiscus luteus. AB - The chloroplasts of chlorophytic and chromophytic plants exhibit significant morphological and biochemical differences. Presently, it is impossible to compare the influence of ctDNA on the structure and function of organelles within these two phylogenetic groups for no data exist in the literature on the profile of protein products synthesized by a chromophytic plastid. In this paper, the chloroplast DNA coded proteins of the chromophytic plant Olisthodiscus luteus are investigated by labeling isolated chloroplasts in vitro. Isolated plastids of excellent morphological condition are pulse labeled with [35S]methionine. Approximately 100 proteins are detected by two-dimensional gel electrophoresis and fluorography. However, these isolated plastids have a number of unusual characteristics: (1) they are photosynthetically inactive; (2) in vitro protein synthesis is light independent; (3) all proteins synthesized in vitro are membrane associated. PMID- 4016072 TI - In vivo chloroplast protein synthesis by the chromophytic alga Olisthodiscus luteus. AB - Information on the ctDNA protein coding profile of the Chlorophyta, Rhodophyta, and Chromophyta might provide clues to the evolutionary mechanism(s) by which plants diverged into these three phylogenetic groups. The purpose of this study was to examine the ctDNA protein coding profile of the chromophytic plant Olisthodiscus luteus. Whole cells were labeled in the presence of cycloheximide, an inhibitor of cytoplasmic protein synthesis. Control experiments demonstrate that the chloroplast proteins labeled in vivo by this technique form a distinct subset of the total proteins synthesized by the cell. Approximately 50 plastid proteins (35 soluble, 15 membrane) were detected after two-dimensional gel electrophoresis and fluorography. Three ctDNA-coded proteins, the large subunit of ribulosebisphosphate carboxylase, the apoprotein of the P700-chlorophyll a protein complex, and the "photogene" were identified. These proteins are also coded by chlorophytic ctDNA. Unexpectedly, the ctDNA of Olisthodiscus was shown to code for the small subunit of ribulosebisphosphate carboxylase. The gene for this enzyme subunit is nuclear coded in all chlorophytic plants that have been analyzed. PMID- 4016073 TI - Enzymatic protein carboxyl methylation at physiological pH: cyclic imide formation explains rapid methyl turnover. AB - At pH 7.4, 37 degrees C, bovine brain protein carboxyl methyltransferase transiently methylates deamidated adrenocorticotropin. The methylation occurs at the alpha-carboxyl group of an atypical beta-carboxyl-linked isoaspartyl residue (position 25). Several lines of evidence indicate that the immediate product of demethylation is an aspartyl cyclic imide involving positions 25 and 26. The evidence includes (1) the rapid rate of methyl ester hydrolysis, which is consistent with intramolecular catalysis, (2) the inability of the demethylated product to be remethylated, (3) the charge of this product, and (4) its rate of breakdown. The eventual hydrolysis of the cyclic imide produces a 30/70 mixture of peptides containing either alpha- or beta-carboxyl-linked aspartyl residues, respectively. Cyclic imide formation is nonenzymatic and can explain the unusual lability of mammalian protein methyl esters in general. These findings suggest that protein carboxyl methylation in mammalian tissues is not a simple on/off reversible modification as it apparently is in chemotactic bacteria. Carboxyl methylation may serve to activate selected protein carboxyl groups for subsequent longer lasting modifications, possibly subserving a role in protein repair, degradation, cross-linking, or some other as yet undiscovered alteration of protein structure. PMID- 4016074 TI - Encapsulation of hemoglobin in phospholipid liposomes: characterization and stability. AB - Hemoglobin is encapsulated in liposomes of different lipid composition. The resulting dispersion consists primarily of multilamellar liposomes (hemosomes) of a wide particle size distribution (diameter ranging mainly between 0.1 and 1 micron). The encapsulation efficiency is significantly larger with liposomes containing negatively charged lipids as compared to liposomes made of phosphatidylcholine. The integrity of the phospholipid bilayer is maintained in the presence of hemoglobin. The reaction rate of CO binding to encapsulated hemoglobin is reduced compared to that of free hemoglobin, but it is still greater than that observed in red blood cells. Hemoglobin encapsulated in liposomes made from negatively charged phospholipids is less stable than hemoglobin entrapped in isoelectric phosphatidylcholine. The instability of hemoglobin is due to the protein interacting with the negatively charged lipid bilayer. This interaction leads in turn to hemoglobin denaturation, possibly involving the dissociation of the heme group from the heme-globin complex. The nature of the negatively charged phospholipid is important in promoting the interaction with hemoglobin, the effect being in the order phosphatidic acid greater than phosphatidylinositol congruent to phosphatidylglycerol greater than phosphatidylserine. The presence of equimolar amounts of cholesterol in the phospholipid bilayer has a stabilizing effect on hemoglobin. This effect is pronounced with saturated phospholipids, but it is also observed, though to a lesser extent, with unsaturated ones, indicating that the bilayer fluidity has a modulating effect. The presence of cholesterol possibly interferes with secondary interactions following the binding of hemoglobin to the negatively charged lipid bilayer. PMID- 4016075 TI - Conformation and stability of the anion transport protein of human erythrocyte membranes. AB - The conformation and stability of purified preparations of band 3, the anion transport protein of human erythrocyte membranes, and its constituent proteolytic subfragments have been studied by circular dichroism. Band 3, purified in the presence of the nonionic detergent n-dodecyl octaethylene glycol monoether (C12E8), had an alpha-helical content of 46%. Denaturation of purified band 3 with guanidine hydrochloride occurred in two phases, one reflecting much more resistance to denaturation than the other. Band 3 can be separated into two domains by limited in situ proteolytic cleavage. The carboxyl-terminal membrane associated domain (Mr 55 000) purified in C12E8 contained 58% alpha-helix and was very resistant to denaturation by guanidine hydrochloride. The purified amino terminal, cytoplasmic domain (Mr 41 000) contained 27% alpha-helix and was completely converted to a random-coil conformation by 3 M guanidine hydrochloride. The two phases of denaturation observed for intact band 3 corresponded to the two domains of the protein. Irreversible heat denaturation of purified band 3 occurred with half-maximal change in theta 222.5 at 48 degrees C. Covalent attachment of the anion transport inhibitor 4,4'-diisothiocyanostilbene 2,2'-disulfonate to band 3 had little effect on the circular dichroism spectra of band 3 or the membrane-associated domain but resulted in stabilization of band 3 to heat denaturation (half-maximal change in theta 222.5 = 61 degrees C). Circular dichroism studies of membranes that had been digested extensively with proteolytic enzymes and stripped of all extrinsic fragments revealed that the portions of red cell membrane proteins that are embedded in the lipid bilayer contain a very high (86-94%) content of alpha-helix. PMID- 4016076 TI - Lipid transfer between phosphatidylcholine vesicles and human erythrocytes: exponential decrease in rate with increasing acyl chain length. AB - The rate of phospholipid transfer from sonicated phospholipid vesicles to human erythrocytes has been studied as a function of membrane concentration and lipid acyl chain composition. Phospholipid transfer exhibits saturable first-order kinetics with respect to both cell and vesicle membrane concentrations. This kinetic behavior is consistent either with transfer during transient contact between cell and vesicle surfaces (but only if the fraction of the cell surface susceptible to such interaction is small) or with transfer of monomers through the aqueous phase. The acyl chain composition of the transferred phospholipid affects the transfer kinetics profoundly; for homologous saturated phosphatidylcholines, the rate of transfer decreases exponentially with increasing acyl chain length. This behavior is consistent with passage of phospholipid monomers through a polar phase, which might be the bulk aqueous phase( as in the monomer transfer model) or the hydrated head-group regions of a cell-vesicle complex (transient collision model). Collisional transfer also predicts that intercell transfer of phospholipids should be slow compared to cell vesicle transfer, as surface charge and steric effects should prevent close apposition of donor and acceptor membranes. This is not found; dilauroylphosphatidylcholine transfers rapidly between red cells. Thus, the observed relationship between acyl chain length and intermembrane phospholipid transfer rates likely reflects the energetics of monomer transfer through the aqueous phase. PMID- 4016077 TI - Determination of the topography of cytochrome b5 in lipid vesicles by fluorescence quenching. AB - Cytochrome b5, a protein isolated from the endoplasmic reticulum by detergent extraction, interacts spontaneously with small unilamellar phosphatidylcholine vesicles. When the vesicles are made from 1-palmitoyl-2-oleoylphosphatidylcholine (POPC), the tryptophan fluorescence of the cytochrome is enhanced, and when they are made from 1-palmitoyl-2-(dibromostearoyl) phosphatidylcholine (BRPC), the fluorescence is quenched. A series of BRPC were synthesized with bromine atoms at the 6,7, 9,10, 11,12 or 15,16 positions. The vesicles synthesized from each of these lipids were similar in size to those made from POPC. The relative fluorescence intensities of the cytochrome b5 in POPC and 6,7-, 9,10-, 11,12- and 15,16- BRPC were 100, 19.4, 29.4, 37.1, and 54.0, respectively. These data suggest that the exposed tryptophan(s) is (are) at a depth of 0.7 nm below the surface of the vesicle. Bromine is a collisional quencher; hence, these data may indicate the relative position of the lipid annulus around the protein rather than the depth of the protein below the average vesicle surface. Cytochrome b5 contains three potentially fluorescent tryptophans, and determinations of fluorescent quantum yield indicate all three potentially fluorescent tryptophans, and determinations of fluorescent quantum yield indicate all three are fluorescent with an average quantum yield, when in POPC vesicles, of 0.21. Fluorescence lifetime measurements by the demodulation technique indicated heterogeneity of fluorescence lifetimes in all vesicles. The lifetimes in the BRPC vesicles ranged from 2.0 to 2.4 ns compared to a value of 3.3 ns in POPC.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4016078 TI - Polymorphic phase behavior of cardiolipin derivatives studied by 31P NMR and X ray diffraction. AB - The polymorphic phase behavior of cardiolipin (diphosphatidylglycerol) analogues with two to five chains per phospholipid head group, namely, dilysocardiolipin, monolysocardiolipin, cardiolipin, and acylcardiolipin, respectively, has been studied by 31P NMR and X-ray diffraction. Dilysocardiolipin dispersions at low salt concentration are micellar, and a transition to a lamellar phase takes place between 1 and 2 M NaCl. From light-scattering measurements, it is also found that a transition takes place from the micellar state with a midpoint at 5.2 mM CaCl2, 0.95 M HClO4, and 1.5 M NaCl. Monolysocardiolipin dispersions are lamellar throughout the concentration range from zero to saturated NaCl. Cardiolipin dispersions undergo a transition from a lamellar to an inverted hexagonal phase between 1 and 2 M NaCl. Acylcardiolipin dispersions are in an inverted hexagonal phase throughout the concentration range from zero to saturated NaCl. The chemical shift anisotropies of both phosphate groups in dilysocardiolipin and of one of the phosphate groups in monolysocardiolipin are drastically reduced in the lamellar phase, indicating a different conformation of the phosphatidyl head group from that normally found in diacyl phospholipid bilayers. The results provide strong support for the "shape" concept of lipid polymorphism when viewed in its most general form including configurational entropy, hydrophobic effects, etc. and indicate the importance of head-group interactions in determining the lipid phase behavior. PMID- 4016079 TI - Characterization of initiation factor 3 from wheat germ. 1. Effects of proteolysis on activity and subunit composition. AB - Wheat germ initiation factor 3 (eIF-3) is a large (15 S) particle containing 10 subunits with molecular weights ranging from 28 000 to 116 000. Two forms of wheat germ eIF-3 which differ in ability to support polypeptide synthesis in vitro have been obtained by chromatography on carboxymethyl-Sephadex (CM Sephadex). The less active form is not retained on CM-Sephadex in 50 mM KCl and contains lower amounts of two subunits, the 116 000-dalton polypeptide (pp116) and the 36 000-dalton polypeptide (pp36). The more active form is retained on CM Sephadex in 50 mM KCl and is eluted by 150 mM KCl. Treatment of the more active form with small amounts of trypsin results in a rapid degradation of four of the subunits (pp116, pp107, pp87, and pp36) and in a rapid loss in the ability to support polypeptide synthesis. Trypsin treatment also diminishes the ability of eIF-3 to support the binding of mRNA to 40S ribosomal subunits. These findings indicate that pp116, pp107, pp87, and pp36 are in exposed positions in the eIF-3 particle and that pp116 and/or pp36 are essential for activity. PMID- 4016080 TI - Phenylalanine hydroxylase: absolute configuration and source of oxygen of the 4a hydroxytetrahydropterin species. AB - The formation of tyrosine from phenylalanine catalyzed by rat liver phenylalanine hydroxylase is coupled to the generation of a 4a-hydroxy adduct from the requisite tetrahydropterin cofactor. As indicated by its circular dichroism (CD) spectrum, the optical activity of the adduct generated from racemic 6 methyltetrahydropterin requires stereoselectivity of the oxygenation. The absolute configuration of this new stereocenter is 4a(S)-hydroxy-6(RS) methyltetrahydropterin by analogy to the CD spectrum of one of the four stereoisomers of 5-deaza-4a-hydroxy-6-methyltetrahydropterin. The source of the 4a-hydroxy oxygen is O2, as demonstrated by the observation of a 18O-induced 13C shift in the 13C NMR spectrum of the adduct when generated from [4a-13C]-6 methyltetrahydropterin and 18O2. PMID- 4016081 TI - Circular dichroic evidence for an ordered sequence of ligand/binding site interactions in the catalytic reaction of the cAMP-dependent protein kinase. AB - A limiting requirement for substrate specificity of the cAMP-dependent protein kinase is the presence of one or two basic residues located to the N-terminal side of the target substrate serine. Furthermore, circular dichroic (CD) studies have shown that binding of protein substrate involves a series of at least two independent conformational changes in the enzyme, each of which is initiated by a recognition signal on the substrate protein. The present study attempts to elucidate further the complete sequence of enzyme/ligand interactions by using the synthetic substrate peptide Kemptide and analogues differing from it at crucial points in the sequence: the Ala-peptide, where alanine is substituted for the target serine, and D-Ser-Kemptide, where the target serine is in the D rather than the L configuration. Examination of the effects of binding of these substrates on the intrinsic UV CD of the enzyme and the induced CD in the presence of Blue Dextran has revealed a third step in the substrate/enzyme binding interaction. Although sections of the conformational change at the active site are dependent on the basic subsite and the serine hydroxyl group on the peptide, respectively, the complete conformational change requires that the substrate be bound in random coil conformation. Where this does not occur, the kinetics show that the peptide will not act either as substrate or as inhibitor of the enzyme. Further, the interaction between the serine hydroxyl group and an enzyme tyrosine residue, previously observed, appears to be dependent on the correct orientation as well as the mere presence of the target -OH group.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4016082 TI - Probable role of amphiphilicity in the binding of mastoparan to calmodulin. AB - Two-dimensional helical wheel diagrams and calculations of mean hydrophobic moments show mastoparan, mastoparan X, and Polistes mastoparan to have all the properties expected for amphiphilic helices. Circular dichroic properties are consistent with a random form for these peptides in dilute aqueous solution, but greater than 50% helix is apparent when the peptides are dissolved in 70% trifluoroethanol/water mixtures (v/v) or when the peptides are bound to calmodulin. Changes in the fluorescence spectra, anisotropy, and accessibility of tryptophan whose indole side chain is on the apolar surface of the amphiphilic helix imply a significant role for the apolar surface in the binding of the mastoparans and another amphiphilic peptide, melittin, to calmodulin. These data provide a useful model for designing high-affinity synthetic peptide inhibitors of calmodulin. PMID- 4016083 TI - Quaternary structure has little influence on spin states in mixed-spin human methemoglobins. AB - A key feature of the Perutz stereochemical model for cooperativity in hemoglobin is a strong coupling between quaternary structure and the spin state of the heme iron [Perutz, M. F. (1979) Annu. Rev. Biochem. 48, 327-386]. While this coupling appears to be present for carp azide methemoglobin, it should also be present for all liganded forms of human methemoglobin that exhibit a thermal high-spin in equilibrium low-spin equilibrium. To test this hypothesis, we have measured the changes in spin equilibria upon conversion of six mixed-spin forms of human methemoglobin from the R (high-affinity) to the T (low-affinity) quaternary structure by addition of inositol hexaphosphate. These experiments were done with a sensitive superconducting magnetic susceptibility instrument on solutions at 20 degrees C in 20 mM maleate buffer, pH 6. The data show zero or small increases in high-spin content upon switching from R to T, changes that are equivalent to a relative stabilization of the high-spin form by only 0-300 cal mol-1 heme-1. These changes in energy are far less than the 1200 cal mol-1 heme-1 predicted from the Perutz stereochemical model [Cho, K. C., & Hopfield, J. J. (1979) Biochemistry 18, 5826-5833]. That is, these data do not support a view that the low affinity of the T state is due to restraints acting through the iron-proximal histidine linkage. The mechanistic implications of these results and the differences between species and ferric ligands are discussed. PMID- 4016084 TI - Steady-state carbon-13 nuclear magnetic resonance spectra of acyl-alpha chymotrypsin. AB - When [13C]carbonyl-enriched p-nitrophenyl 5-n-propyl-2-furoate is incubated with alpha-chymotrypsin, a new peak appears in the 13C NMR spectrum. On the basis of its position and the fact that it is "chased" with unlabeled substrate, we conclude that this new signal is due to the acyl-enzyme intermediate. In spectra taken during steady-state turnover, the acyl-enzyme ester carbonyl 13C chemical shift displays a pH dependence that fits to a titration curve with an apparent pK of 7.1 (0.1). The apparent pK of the kcat vs. pH curve for enzyme-catalyzed hydrolysis of the same substrate under conditions differing only in reactant concentration is 7.0 (0.1). We have found no spectral evidence for a tetrahedral intermediate. PMID- 4016085 TI - Influence of monovalent cation transport on anabolism of glycosphingolipids in cultured human fibroblasts. AB - We have reported [Saito, M., Saito, M., & Rosenberg, A. (1984) Biochemistry 23, 1043-1046] that the monovalent cationic ionophore monensin reduced the incorporation of labeled galactose into oligosaccharidyl glycosphingolipids (globotriaosylceramide, globotetraosylceramide, and gangliosides) and induced a cellular accumulation of glucosyl- and lactosylceramide in cultured diploid human fibroblasts. We have undertaken further studies on the effects of monensin and made comparison with the effects of related monovalent cation transporters on plasma membrane glycosphingolipid anabolism in human fibroblasts. Our results demonstrate that ionic flux can markedly influence glycosphingolipid synthesis, and they indicate that, like glycoprotein, the sites of glycosylation of the initial, precursor glycosphingolipids are different from the sites of higher glycosylation. At a concentration of 10(-7) M, monensin induced the maximum inhibition of incorporation of labeled galactose into polyglycosyl sphingolipids: globotriaosylceramide, globotetraosylceramide, and gangliosides; increased incorporation of labeled galactose into glucosyl- and lactosylceramide was clearly evident, and their content rose measurably in the cell at concentrations of monensin as low as 10(-8) M. These effects of monensin were reversible. Incorporation of labeled galactose into higher glycosylated neutral glycosphingolipids and gangliosides slowly resumed, and the accumulated glycosylceramide diminished after removal of monensin from the culture medium. Ouabain (plasma membrane Na+,K+-ATPase inhibitor) and A23187 (Ca2+ ionophore) also caused a rapid increase in incorporation of labeled hexose into glucosylceramide and decreased its incorporation into higher neutral glycosphingolipids and into gangliosides.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4016086 TI - Interaction of calmodulin with the red cell and its membrane skeleton and with spectrin. AB - The binding of calmodulin to red cell membrane cytoskeletons and to purified spectrin from red cells and bovine brain spectrin (fodrin) has been examined. Under physiological solvent conditions binding can be measured by ultracentrifugal pelleting assays. The membrane cytoskeletons contained a single class of binding sites, with a concentration similar to that of spectrin dimers and an association constant of 1.5 X 10(5) M-1. Binding is calcium dependent and is suppressed by the calmodulin inhibitor trifluoperazine. The binding showed a marked dependence on ionic strength, with a maximum at 0.05 M, and a steep dependence on pH, with a maximum at pH 6.5. It was unaffected by 5 mM magnesium. An azidocalmodulin derivative, under the conditions of our experiments, did not label the spectrin-containing complex, although it could be used to demonstrate binding to fodrin. Binding of calmodulin to spectrin tetramers and fodrin in solution could be demonstrated by a pelleting assay after addition of F-actin. Calculations (which are necessarily rough) suggest that at the free calcium concentration prevailing in a normal red cell about 1 in 20 of the calmodulin binding sites in spectrin will be occupied; this proportion will rise rapidly with increasing intracellular calcium. To determine whether inhibition of calmodulin binding to red cell proteins disturbs the control of cell shape, as has been suggested, calcium ions were removed from the cell by addition of an ionophore and of ethylene glycol bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid to the external medium. This did not affect the discoid shape. Trifluoperazine still induced stomatocytosis, exactly as in untreated cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4016087 TI - Human brain monoamine oxidase type B: mechanism of deamination as probed by steady-state methods. AB - Recently, evidence has been published which suggests that [Husain, M., Edmondson, D. E., & Singer, T.P. (1982) Biochemistry 21, 595-600] monoamine oxidase [amine:oxygen oxidoreductase (MAO), EC 1.4.3.4] deaminates phenylethylamine and benzylamine via two distinct kinetic pathways which involve either binary or ternary complex formation, respectively. These conclusions were drawn largely from stopped-flow kinetic analysis performed on purified enzyme removed from its native membrane and in the presence of the inhibitory detergent Triton X-100. In this study, d-amphetamine and alternative substrates were used as steady-state probes of the kinetics of deamination by the B form of human brain MAO using native membrane-bound enzyme. Initial velocity studies showed mixed-type patterns for amphetamine inhibition of phenylethylamine, tryptamine, and tyramine when either amine or oxygen was the varied substrate. Slope and intercept vs. amphetamine concentration replots were linear in all cases except for phenylethylamine (hyperbolic); Ki values obtained from linear replots of slope or intercept values were comparable. In contrast, amphetamine was a competitive inhibitor of benzylamine deamination when amine concentration was varied and uncompetitive when oxygen concentration was varied; slope and intercept replots were linear for both. When benzylamine was the alternative substrate inhibitor and tyramine and tryptamine deamination was measured, mixed-type inhibition patterns were obtained when either amine or oxygen concentration was varied; replots of slope and intercept were linear in all cases.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4016088 TI - Tryptophan imaging of membrane proteins. AB - A theoretical analysis of resonance energy transfer between protein tryptophan and the n-(9-anthroyloxy) (AO) fatty acid probes has been carried out to evaluate its potential use in determining the tryptophan distribution in membrane proteins. The Forster theory for two-dimensional energy transfer was formulated to calculate multiple donor (tryptophan) transfer efficiencies to ensembles of AO probes at different depths in the bilayer. The variation of transfer efficiency with AO probe depth is found to be a sensitive function of tryptophan position and the protein radius but not the dipole-dipole orientation factor or the decay heterogeneity of the donor. For single tryptophan-containing proteins the model predicts that the tryptophan position can be determined with a precision of about 2 A. Although for multiple tryptophans there is appreciable deterioration in resolution, it is still possible to determine the essential features of the distribution such as its first two moments. The positions determined by this method are the projections of the tryptophan positions on a plane perpendicular to the membrane surface, since the probes distribute uniformly around the protein. To analyze the data, a Monte Carlo approach has been developed to search for tryptophan distributions compatible with the observed efficiencies and to display the results in terms of a tryptophan density map. It is shown that even for cases in which little is known about the quantum yield distribution, significant information can be determined about the tryptophan spatial distribution. PMID- 4016089 TI - Energy-transfer study of cytochrome b5 using the anthroyloxy fatty acid membrane probes. AB - Resonance energy transfer was used to study the structure of cytochrome b5 and its nonpolar segment reconstituted into sonicated vesicles of dimyristoylphosphatidylcholine. The n-(9-anthroyloxy) (AO) fatty acid probes were added to these vesicles, and energy-transfer measurements were carried out between tryptophan and AO, tryptophan and the heme moiety of cytochrome b5, and AO and heme. Results of these measurements were analyzed by using the methods outlined in the previous paper [Kleinfeld, A. M. (1985) Biochemistry (preceding paper in this issue)]. We find, in agreement with Fleming et al. [Fleming, P. J., Koppel, D. E., Lau, A. L. Y., & Strittmatter, P. (1979) Biochemistry 18, 5458 5464], that the fluorescent tryptophan in both forms of the protein is buried about 20 A from the surface and that most of the fluorescence is associated with a single tryptophan. The results are consistent with the AO probe distance of closest approach to the protein, greater for whole b5 than for the nonpolar peptide. The tryptophan-heme and AO-heme measurements indicate that the heme moiety is about 15 A from the surface of the membrane. The agreement of our results with the previous studies supports the description of tryptophan-AO energy transfer outlined in the preceding paper. PMID- 4016090 TI - Fusion of phospholipid vesicles induced by muscle glyceraldehyde-3-phosphate dehydrogenase in the absence of calcium. AB - Ca2+-induced fusion of phospholipid vesicles (phosphatidylcholine/phosphatidic acid, 9:1 mol/mol) prepared by ethanolic injection was followed by five different procedures: resonance energy transfer, light scattering, electron microscopy, intermixing of aqueous content, and gel filtration through Sepharose 4-B. The five methods gave concordant results, showing that vesicles containing only 10% phosphatidic acid can be induced to fuse by millimolar concentrations of Ca2+. When the fusing capability of several soluble proteins was assayed, it was found that concanavalin A, bovine serum albumin, ribonuclease, and protease were inactive. On the other hand, lysozyme, L-lactic dehydrogenase, and muscle and yeast glyceraldehyde-3-phosphate dehydrogenase were capable of inducing vesicle fusion. Glyceraldehyde-3-phosphate dehydrogenase from rabbit muscle, the most extensively studied protein, proved to be very effective: 0.1 microM was enough to induce complete intermixing of bilayer phospholipid vesicles. Under conditions used in this work, fusion was accompanied by leakage of internal contents. The fusing capability of glyceraldehyde-3-phosphate dehydrogenase was not affected by 5 mM ethylenediaminetetraacetic acid. The Ca2+ concentration in the medium, as determined by atomic absorption spectroscopy, was 5 ppm. Heat-denatured enzyme was incapable of inducing fusion. We conclude that glyceraldehyde-3-phosphate dehydrogenase is a soluble protein inherently endowed with the capability of fusing phospholipid vesicles. PMID- 4016091 TI - Secondary structure and assembly mechanism of an oligomeric channel protein. AB - The alpha-toxin of Staphylococcus aureus is secreted as a water-soluble, monomeric polypeptide (Mr 33 182) that can assemble into an oligomeric membrane channel. By chemical cross-linking, we have confirmed that the major form of the channel is a hexamer. The circular dichroism spectrum of this hexamer in detergent revealed that it contains a high proportion of beta-sheet that we deduce must lie within the lipid bilayer when the protein is associated with membranes. The circular dichroism spectrum of the monomeric toxin in the presence or absence of detergent was closely similar to the spectrum of the hexamer, suggesting that the secondary structure of the polypeptide is little changed on assembly. Results of experiments involving limited proteolysis of the monomer and hexamer are consistent with the idea that assembly involves the movement of two rigid domains about a hinge located near the midpoint of the polypeptide chain. The hydrophilic monomer is thereby converted to an amphipathic rod that becomes a subunit of the hexamer. PMID- 4016092 TI - Conformational flexibility of neurophysin as investigated by local motions of fluorophores. Relationships with neurohypophyseal hormone binding. AB - Flexibility of various structural domains of neurophysin and neurophysin neurohypophyseal hormone complexes has been investigated through the fast rotational motion of fluorophores in highly viscous medium. Despite seven intrachain disulfide links, it is shown that some domains of neurophysin remain highly flexible. Dimerization of neurophysin does not affect the structural integrity of the individual subunits, each subdomain being conformationally equivalent within each protomer of the unliganded dimer. The absence of heterogeneous fluorescence anisotropy precludes the existence of a dimer tautomerization equilibrium. Binding of the hormonal ligands to neurophysin dimer promotes a large conformational change over the whole protein structure as assessed by differential alterations of the flexibility-rigidity and intrasegmental interaction properties of domains that do not participate directly to the dimerization/binding areas. The order of free-energy coupling between ligand binding and protein subunit association has been evaluated. Data are consistent with a model in which the first mole of bound ligand stabilizes the dimer by increasing the intersubunit contacts while the second mole of ligand induces most of the described conformational change. Accordingly, the positive cooperativity between the two dimeric binding sites is linked mainly to the binding of the second ligand. The induced structural change is perceived differently by each subunit as assessed by opposite local motions of Tyr49 in each liganded protomer and leads to the formation of a dimeric complex with a global pseudospherical symmetry although containing domains of local asymmetry. PMID- 4016093 TI - Purification, characterization, and activation of the glucocorticoid-receptor complex from rat kidney cortex. AB - The unactivated molybdate-stabilized glucocorticoid receptor (GcR) was purified from rat kidney cortex cytosol (RKcC) by using a modification of the procedure previously described by this laboratory for rat hepatic receptor. The purification includes affinity chromatography, gel filtration, and ion-exchange chromatography. The final preparation (approximately 1000-fold pure as determined from specific radioactivity) was used in subsequent physicochemical and functional analyses. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) showed a single heavily Coomassie-stained band at 90 kilodaltons. Density gradient ultracentrifugation indicated a sedimentation coefficient of 10.5 +/- 0.05 S (n = 2). Chromatography on an analytical gel filtration column produced a Stokes radius (Rs) of 6.4 +/- 0.07 nm (n = 5). The Rs was unchanged when the molybdate-stabilized GcR was analyzed in the presence of 400 mM KCl or when analyzed in the unpurified (cytosolic) state. In contrast, the hepatic GcR was observed to exist as a larger form in cytosol (7.7 +/- 0.2 nm). Following purification, or upon gel filtration analysis under hypertonic conditions, the Rs was similar to that of the unpurified RKcC GcR. Following removal of molybdate from RKcC GcR and thermal activation (25 degrees C/30 min), DNA-cellulose binding increased 1.5-2-fold over the unheated control. Addition of RKcC or hepatic cytosol (endogenous receptors thermally denatured at 90 degrees C/30 min or presaturated with 10(-7) M radioinert ligand) during thermal activation increased DNA-cellulose binding an additional 2-6-fold beyond the heated control.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4016094 TI - Inhibition of deoxyhemoglobin S polymerization by biaromatic peptides found to associate with the hemoglobin molecule at a preferred site. AB - Association of three succinylated biaromatic peptides with deoxyhemoglobin has been measured. These peptides composed of indolyl or phenyl rings were found to have delta G values for their binding to deoxyhemoglobin between -2.9 and -3.4 kcal/mol at 23 degrees C. Binding experiments among these peptides demonstrate one preferred site, one of strongest binding of the peptide to the Hb molecule, as well as the existence of one or more weaker binding sites. Both aromatic side chains and at least one of the terminal carboxyl groups of the succinylated peptides are involved in the interactions with the hemoglobin (Hb) side chains at the preferred binding site. The latter also was found to be capable of binding monocyclic moieties of sufficient hydrophobicity, i.e., indolyl ring compounds. Increases in deoxyhemoglobin S (deoxy-HbS) solubilities in the presence of these three biaromatic peptides show a strong correlation between the values of their dissociation constants and their ability to destabilize deoxy-HbS aggregation. The symmetric site to which the peptides bind must be located at or near a contact site needed to stabilize the deoxy-HbS polymer. PMID- 4016095 TI - Formation and characterization of aurothioneins: Au,Zn,Cd-thionein, Au,Cd thionein, and (thiomalato-Au)chi-thionein. AB - Three gold-containing thioneins (Au,Zn,Cd-Th, Au,Cd-Th, and (TmSAu)chi Th, where Th = thionein and TmS = thiomalate) have been prepared by the reactions of horse kidney Zn,Cd-thionein with gold thiomalate (AuSTm). When thionein was present in excess, the thiomalate ligand was displaced and the protein chelated the gold in a bidentate fashion. Primarily zinc but also some cadmium was displaced to form Au,Zn,Cd-Th or Au,Cd-Th. Excess AuSTm reacted to form (TmSAu)chi-thionein with monodentate coordination of the protein to each bound gold, retention of the thiomalate, loss of zinc and cadmium, and an increase in the Stokes radius of the product. EXAFS/XANES studies of Au,Zn,Cd-Th and (TmSAu)chi Th established that the oxidation states and coordination environments of gold were Au(I)S2 and that the gold-sulfur bond distances were 229 and 230 pm, respectively. Radioimmunoassay established that the aurothioneins retained their antigenicity to native metallothionein antibodies. Metal exchange reactions with gold were complete within 5-10 min when Zincon or 4-(2-pyridylazo) resorcinol was used to monitor Cd2+ and Zn2+ displacement. PMID- 4016096 TI - Optical model studies of the salt-induced 10-30-nm fiber transition in chromatin. AB - Fractionated chicken erythrocyte chromatin fibers consisting of 10-mer and 75-mer polynucleosomes have been studied by flow birefringence and viscosity over a range of Na+ and Mg2+ ion concentrations sufficient to span the 10-30-nm fiber transition. Negative intrinsic flow bifringence was observed under all solvent conditions investigated. The intrinsic birefringence, obtained from the reduced birefringence to intrinsic viscosity ratio, was used to evaluate various optical models for the DNA conformation in the fiber. Results are consistent with an extended chromatosome-linker "necklace" model for the unfolded, low-salt fiber and with a solenoidal model of edge-stacked chromatosomes for the condensed fiber at high salts. These results are consistent with and independently corroborative of similar models based upon electric dichroism and neutron scattering reported by others. PMID- 4016097 TI - Gramicidin S synthetase. Temperature dependence and thermodynamic parameters of substrate amino acid activation reactions. AB - In the biosynthesis of the cyclic decapeptide antibiotic gramicidin S, the constituent amino acids are activated by a two-step mechanism involving aminoacyl adenylate and thio ester formation which are both reversible processes. The dissociation constants (KD) for the gramicidin S synthetase-substrate amino acid thio ester complexes are 100-1000-fold lower compared to the KM data of the preceding aminoacyl adenylate reactions. The affinity for these substrates is appreciably higher at the thio template sites than at the aminoacyl adenylate reaction centers. Therefore, the activation equilibria are quantitatively shifted toward thio ester formation. A set of thermodynamic parameters for the activation processes was determined from the temperature dependence of the KM and KD data. Reaction enthalpies were obtained from a van't Hoff analysis of these constants. delta G degree for the substrate activation reactions of the heavy enzyme of gramicidin S synthetase (GS 2) is predominantly controlled by entropy contributions. In contrast, the overall activation and concomitant racemization of phenylalanine by phenylalanine racemase (GS 1) are exothermic processes which are distinguished by a small negative reaction entropy. PMID- 4016098 TI - 4,4'-Bis[8-(phenylamino)naphthalene-1-sulfonate] binding to human thrombins: a sensitive exo site fluorescent affinity probe. AB - The binding of the fluorescent probe 4,4'-bis[8-(phenylamino)naphthalene-1 sulfonate] (bis-ANS) to human alpha- and gamma-thrombins was investigated. Bis ANS binds in a 1:1 complex to both forms of the enzyme, with Kd = 14.8 +/- 2.2 microM and 5.8 +/- 1.0 microM for alpha- and gamma-thrombin, respectively, at pH 7.0 [25 mM tris(hydroxymethyl)aminomethane, 0.15 M NaC1]. Fluorescence changes upon complexation included a considerable (approximately 30-nm) blue shift in the fluorescence emission maximum as well as a dramatic increase in the fluorescence emission intensity: a 70-fold enhancement was observed with alpha-thrombin vs. a approximately 220-fold enhancement with gamma-thrombin. Proflavin was not displaced upon bis-ANS binding. The unknown thrombin effectors ATP, Ca(II)ATP, Co(III)ATP, phosphate, and pyrophosphate bound with enhancement of the fluorescence of the bis-ANS-alpha-thrombin complex. The two inhibitors benzamidine and p-chlorobenzylamine as well as heparin caused decreases in bis ANS-thrombin fluorescence: valerylamidine had no effect on the fluorescence of the bis-ANS-thrombin complex. Kinetic measurements with two chromogenic substrates, S-2238 and S-2160, indicated that bis-ANS acts as a partial noncompetitive inhibitor of thrombin amidase activity. The kinetic evidence combined with the ligand binding results suggests that bis-ANS does not overlap the catalytic site. The fluorophore ANS complexed with equal affinity to both alpha- and gamma-thrombins (Kd = 24 +/- 4 microM); however, the gamma-thrombin ANS complex emission at 470 nm was enhanced 26% more than that for the alpha form. PMID- 4016099 TI - Human leukocyte cathepsin G. Subsite mapping with 4-nitroanilides, chemical modification, and effect of possible cofactors. AB - The extended substrate binding site of cathepsin G from human leukocytes has been mapped by using a series of peptide 4-nitroanilide substrates. The enzyme has a significant preference for substrates with a P1 Phe over those with the other aromatic amino acids Tyr and Trp. The S2 subsite was mapped with the substrates Suc-Phe-AA-Phe-NA where AA was 13 of the 20 amino acid residues commonly found in proteins. The best residues were Pro and Met. The S3 subsite was mapped with the sequence Suc-AA-Pro-Phe-NA by using 14 different amino acid residues for AA. The two best residues were the isosteric Val and Thr. No significant improvement in reactivity was obtained by extending the substrate to include seven different P4 residues. The kinetic parameters for cathepsin G are significantly slower than those for many other serine proteases. Changes in the reaction conditions and addition of possible cofactors or ligands were in general found to have little effect on the enzymatic activity, while chemical modifications and proteolysis destroyed the activity of cathepsin G. Cathepsin G hydrolyzed peptides containing model desmosine residues and prefers the hydrophobic picolinoyllysine derivative over lysine by substantial margins at both the S4 and S2 subsites but will not tolerate it at S3. Substrates with sequences related to the cathepsin G cleavage site in angiotensin I and angiotensinogen, and the reactive site of alpha 1 antichymotrypsin, were hydrolyzed effectively by enzyme, but with unexceptional rates. Our results indicate that the natural substrate(s) and function(s) of cathepsin G still remain to be discovered. PMID- 4016100 TI - Nuclear magnetic resonance and neutron diffraction studies of the complex of ribonuclease A with uridine vanadate, a transition-state analogue. AB - The complex of ribonuclease A (RNase A) with uridine vanadate (U-V), a transition state analogue, has been studied with 51V and proton NMR spectroscopy in solution and by neutron diffraction in the crystalline state. Upon the addition of aliquots of U-V at pH 6.6, the C epsilon-H resonances of the two active-site histidine residues 119 and 12 decrease in intensity while four new resonances appear. Above pH 8 and below pH 5, these four resonances decrease in intensity as the complex dissociates. These four resonances are assigned to His-119 and His-12 in protonated and unprotonated forms in the RNase-U-V complex. These resonances do not titrate or change in relative area in the pH range 5-8, indicating a slow protonation process, and the extent of protonation remains constant with ca. 58% of His-12 and ca. 26% of His-119 being protonated. The results of diffraction studies show that both His-12 and His-119 occupy well-defined positions in the RNase-U-V complex and that both are protonated. However, while the classic interpretation of the mechanism of action of RNase based on the proposal of Findlay et al. [Findlay, D., Herries, D. G., Mathias, A. P., Rabin, B. R., & Ross, C. A. (1962) Biochem. J. 85, 152-153] requires both His-12 and His-119 to be in axial positions relative to the pentacoordinate transition state, in the diffraction structure His-12 is found to be in an equatorial position, while Lys 41 is close to an axial position. Hydrogen exchange data show that the mobility and accessibility of amides in the RNase-U-V complex do not significantly differ from what was observed in the native enzyme. The results of both proton NMR in solution and neutron diffraction in the crystal are compared and interpreted in terms of the mechanism of action of RNase. PMID- 4016101 TI - Some kinetic characteristics of immobilized protomers and native dimers of mitochondrial malate dehydrogenase: an examination of the enzyme mechanism. AB - Some kinetic characteristics of immobilized native mitochondrial malate dehydrogenase dimers and immobilized protomers, prepared by direct immobilization under conditions yielding complete dissociation without substantial unfolding, were compared to those of native soluble enzyme. Enzyme was covalently immobilized to derivatized porous glass by using a technique which permitted subsequent release of bound enzyme with 0.2 M hydroxylamine at room temperature and pH 7. Kinetic properties of enzyme released from both immobilized dimers and protomers were the same as those for native soluble enzyme, indicating that the immobilization reaction per se did not affect the structure. Both immobilized native dimers and the immobilized protomers exhibited activity with a pH dependence similar to that of native soluble enzyme. The effects of diffusional inhibition were demonstrated for both forms of the immobilized enzyme, especially for the NADH----NAD+ reaction direction. Intrinsic Michaelis constants of both immobilized forms, obtained by extrapolation of apparent values, were similar to those of the soluble enzyme. Furthermore, the effects of inhibitors and effectors with the immobilized forms were the same as those with native soluble enzyme. For example, substrate inhibition was observed with oxalacetate, the inhibitor hydroxymalonate was competitive with ketomalonate and uncompetitive with L malate, and inhibition was observed with citrate in the NADH----NAD+ direction. Thus, immobilization did not appear to suppress the conformational equilibria of either protomers or dimers. More significantly, the kinetic characteristics of the immobilized protomer were indistinguishable from those of the dimer. Hence, a reciprocating mechanism involving subunit interactions cannot be invoked to explain the allosteric behavior of this dimeric enzyme.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4016102 TI - Solvent effects on the stability of A7U7p. AB - The thermodynamics of double-helix formation were measured spectrophotometrically for A7U7 in water at 1 M NaCl and for A7U7p in a variety of solvent mixtures and salt. Comparison of the A7U7 results with calorimetric measurements indicates duplex formation involves intermediate states. For A7U7p between 0.06 and 0.55 M Na+, dTm/d(log [Na+]) = 17.4 degrees C, similar to the value of 19.6 degrees C for poly-(A).poly(U) [Krakauer, H., & Sturtevant, J. M. (1968) Biopolymers 6, 491 512]. At 1 M NaCl, the A7U7p duplex is most stable in 100% water. For 10 mol % solutions, the order for A7U7p duplex stability is ethylene glycol greater than glycerol greater than ethanol greater than 2-propanol greater than dimethyl sulfoxide greater than 1-propanol greater than formamide greater than N,N dimethylformamide greater than urea greater than dioxane. Comparison of changes in stability and thermodynamic parameters with literature results for proteins suggests proteins and A7U7p interact differently with solvent. The results suggest hydrophobic bonding is not a major contributor to the stability of the A7U7p duplex. Comparisons with bulk solvent surface tension suggest the energy of cavity formation is also not a major contributor to duplex stability. PMID- 4016103 TI - Plastocyanin conformation. The effect of nitrotyrosine modification and pH. AB - Plastocyanin isolated from several species including spinach, poplar, and lettuce showed conformational changes both upon reduction and upon lowering the pH as determined by near-ultraviolet absorption and fluorescence measurements. The fluorescence excitation maximum was at 278 nm for all species of plastocyanin measured. In the case of spinach, the emission maximum was at 310-312 nm, similar to a tyrosine residue in solution. The fluorescence intensity increased 22% upon reduction of plastocyanin at pH 7.0. In poplar plastocyanin, the emission maximum was shifted to 335 nm and increased only 10% upon reduction. The 335 nm emission peak observed in poplar plastocyanin is attributed to Tyr 80 which is hydrogen bonded to a carbonyl group on the protein backbone. Tyr 83 was also shown to undergo fluorescence changes upon reduction since the redox state-dependent fluorescence changes decreased for a nitrotyrosine (nitrotyrosine-plastocyanin) derivative of this residue. These results show that the east face of the molecule, which contains both Tyr 80 and 83 as well as a possible binding site, undergoes conformational changes upon reduction. These conformational changes may be involved in promoting smooth electron transport between plastocyanin and its reaction partners. Both the absorption and fluorescence were found to be pH dependent. The quantum yield for fluorescence increased sharply below pH 6 for both oxidized and reduced spinach plastocyanin. This may be related to the appearance of a redox-inactive form of reduced plastocyanin. The conformational changes observed at low pH may provide a mechanism for control of electron transport by the proton gradient. Low concentrations of CaCl2 (10 mM) had no effect on plastocyanin fluorescence. However, addition of 2.7 M (NH4)2SO4 eliminated the redox-dependent fluorescence changes. PMID- 4016104 TI - Organization of ganglioside GM1 in phosphatidylcholine bilayers. AB - Molecules of the ganglioside GM1 are randomly distributed in liquid-crystalline 1 palmitoyl-2-oleoyl phosphatidylcholine bilayers. This conclusion is based on a freeze-etch electron microscopic study using ferritin-conjugated cholera toxin and cholera toxin alone as ganglioside labels. The average number of GM1 molecules under a label is calculated by a novel method from the dependence of the fraction of bilayer area covered by the label on the mole fraction of GM1 in the bilayer. PMID- 4016105 TI - A calorimetry and deuterium NMR study of mixed model membranes of 1-palmitoyl-2 oleylphosphatidylcholine and saturated phosphatidylcholines. AB - Binary phase diagrams have been constructed from differential scanning calorimetry (DSC) data for the systems 1-palmitoyl-2-oleylphosphatidylcholine (POPC)/dimyristoylphosphatidylcholine (DMPC), POPC/dipalmitoylphosphatidylcholine (DPPC) and POPC/distearoylphosphatidylcholine (DSPC). Mixtures of POPC with DMPC exhibit complete miscibility in the gel and liquid crystalline states. Mixtures of POPC with DPPC or with DSPC exhibit gel phase immiscibility over the composition range 0-75% DPPC (or DSPC). These results, when taken together with previous studies of mixtures of phosphatidylcholines, are consistent with the hypothesis that PCs whose order-disorder transition temperatures (Tm values) differ by less than 33 deg. C exhibit gel state miscibility. Those whose Tm values differ by more than 33 deg. C exhibit gel state immiscibility. 2H-NMR spectroscopy has been used to further study mixed model membranes composed of POPC and DPPC, in which either lipid has been labeled with deuterium in the 2-, 10- or 16-position of the palmitoyl chain(s) or in the N-methyls of the choline head group. POPC/DPPC mixtures in the liquid crystalline state are intermediate in order between pure POPC and DPPC at the same temperature. The POPC palmitoyl chain is always more disordered than the palmitoyl chains of DPPC in liquid crystalline POPC/DPPC mixtures. This is attributed to the fact that a POPC palmitoyl chain is constrained by direct bonding to have at least one oleyl chain among its nearest neighbors, while a DPPC palmitoyl chain must have at least one neighboring palmitoyl chain. When liquid crystalline POPC, DPPC and POPC/DPPC mixtures are compared at a reduced temperature (relative to the acyl chain order disorder transition), POPC/DPPC mixtures are more disordered than predicted from the behavior of the pure components, in agreement with enthalpy data derived from DSC studies. Within the temperature range of the broad phase transition of 1:1 POPC/DPPC, a superposition of gel and liquid crystalline spectra is observed for 1:1 POPC/[2H]DPPC, while 1:1[2H]POPC/DPPC exhibits only a liquid crystalline spectrum. Thus, at temperatures within the phase transition region, the liquid crystalline phase is POPC-rich and the gel phase is DPPC-rich. Comparison of the liquid crystalline quadrupole splittings within the thermal phase transition range suggests that mixing of the residual liquid crystalline POPC and DPPC is highly non-ideal. PMID- 4016106 TI - Lecithin:cholesterol acyltransferase regulation. Effect of fluidity of dimyristoylphosphatidylcholine vesicles. AB - The regulation of lecithin:cholesterol acyltransferase by changes in phospholipid bilayer fluidity was investigated using pyrene excimer fluorescence to measure fluidity. Fluidity of dimyristoylphosphatidylcholine (DMPC) unilamellar vesicles was decreased by the addition of up to 20% (mol/mol) cholesterol and increased by the addition of up to 10% (mol/mol) lysoDMPC. When both cholesterol and lysoDMPC are present in the bilayer, their individual effects on fluidity are altered. These changes can be explained by complex formation between cholesterol and phospholipid as in the model of Presti et al. (Presti, F.C., Pace, R.J. and Chan, S.I. (1982) Biochemistry 21, 3831-3335). Lecithin:cholesterol acyltransferase activity with these vesicles as substrates was measured to determine whether activity can be modulated by the fluidity changes of the bilayer on which the enzyme acts. When 10% lysoDMPC, a known lecithin:cholesterol acyltransferase inhibitor, is added to the vesicles, inhibition of activity is observed. When 7.5% lysoDMPC is added to vesicles which contain either 5 or 10% cholesterol, lecithin:cholesterol acyltransferase activity increases. This increase in lecithin:cholesterol acyltransferase activity due to vesicle-fluidity increase is sufficient to overcome the decrease in activity due to lecithin:cholesterol acyltransferase inhibition. This is the first report of the ability of lysoDMPC to increase lecithin:cholesterol acyltransferase activity. PMID- 4016107 TI - Inhibition of platelet aggregation by synthetic phosphatidylcholines: possible involvement of vesiculation of platelet plasma membranes. AB - Synthetic phosphatidylcholines inhibited thrombin-induced aggregation of rabbit platelets. The inhibitory effect of the phosphatidylcholines increased with an increase in the chain-length of the constituent fatty acids up to 12, and then decreased, and C14:0PC and C16:0PC did not inhibit platelet aggregation. The activity of synthetic phosphatidylcholines as to induction of vesiculation of platelet plasma membranes (Kobayashi, T., Okamoto, H., Yamada, J.-I., Setaka, M. and Kwan, T. (1984) Biochim. Biophys. Acta 778, 210-218) and the inhibitory effect of these phosphatidylcholines on platelet aggregation showed the same dependence on the constituent fatty acids of the phosphatidylcholines. The amounts of phosphatidylcholines required for 50% inhibition of platelet aggregation correspond very well to those required for 15% exfoliation of acetylcholinesterase activity, suggesting that there is a close relationship between platelet aggregation and vesiculation of the platelet plasma membrane. The possible mechanism of inhibition of platelet aggregation by synthetic phosphatidylcholines is discussed. PMID- 4016108 TI - The monensin-mediated transport of sodium ions through phospholipid bilayers studied by 23Na-NMR spectroscopy. AB - The monensin-mediated transport of sodium ions through the walls of large unilamellar vesicles of egg phosphatidylcholine was studied using 23Na-NMR and aqueous shift reagents. The transport is dynamic on the NMR time-scale and is strictly first order in monensin over the concentration ranges studied indicating that transport occurs by a 1:1 Na+-ionophore complex. Transport appears to be inhibited by increasing concentrations of Na+. PMID- 4016109 TI - Na+-dependent alkaline earth metal uptake in cardiac sarcolemmal vesicles. AB - The ability of alkaline earth metals (M2+) to substitute for Ca2+ in Na+-Ca2+ exchange was examined in sarcolemmal vesicles isolated from the canine heart. 85Sr2+ and 133Ba2+, in addition to 45Ca2+, were used to determine the characteristics of Na+-M2+ exchange. The Na+i-dependent M2+ uptake was measured as a function of time, with t ranging from 0.5 to 360 s, [Na+]i = 140 mM and [M2+]o = 40 microM. This function was linear for Ca2+ and Sr2+ uptake for approx. 6 s and for Ba2+ for about 60 s. Plateau levels were achieved within 120 s for Ca2+ and Sr2+ but Ba2+ took considerably longer. The Km values for Na+-M2+ exchange, derived from Eadie-Hofstee plots, were 30, 58, and 73 microM for Ca2+, Sr2+ and Ba2+, respectively. The Na+i-dependent uptake of all three ions was stimulated in the presence of 0.36 microM valinomycin. Na+-Ca2+ exchange was also measured in the presence of either 20 microM Sr2+ or 100 microM Ba2+. Both of these ions behaved (at these concentrations) as competitive inhibitors of Na+ Ca2+ exchange with the KI being 32 microM for Sr2+ and 92 microM for Ba2+. Passive efflux was determined by first allowing Na+-M2+ exchange to continue to plateau values and then diluting the loaded vesicles in the presence of EGTA. The rate constants for the passive efflux were 8.4, 6.3 and 4.4 min-1 for Ca2+, Sr2+ and Ba2+, respectively. PMID- 4016110 TI - Pressure effects on mechanisms of charge transport across bilayer membranes. AB - Ion transport across diphytanoylphosphatidylcholine/decane bilayer membranes was measured as a function of hydrostatic pressure over the range 0.1-100 MPa (1-1000 atm). Carrier-mediated K+ conductance decreased with increasing pressure, yielding positive activation volumes of 45 A3 per complex for valinomycin mediated transport, and 74 A3 per complex in the case of nonactin. Comparison with the known pressure dependence of the viscosity of bulk alkane liquids supports the view that the rate limiting step for carrier-mediated transport is the translocation of the carrier-cation complex across an essentially fluid hydrocarbon membrane core. The parameters characterizing transient conductance by the hydrophobic anions, dipicrylaminate and tetraphenylborate, by contrast, were found to be insensitive to pressure over the range available. This was also the case for the steady-state conductance observed at elevated concentrations of both tetraphenylborate and the hydrophobic cation, tetraphenylarsonium. The quasi stationary conductance observed at elevated concentrations of dipicrylaminate did, however, decrease significantly with increasing pressure, indicating a positive activation volume of 20 A3 per ion. Alternative explanations of this more complex response of hydrophobic ions to pressure are considered. Ancillary measurements of specific membrane capacitance revealed an increase of about 10% with an increase of pressure to 100 MPa, yielding an estimated membrane compressibility on the order of 10(-9) m2 X N-1, comparable to that of bulk liquid hydrocarbons. PMID- 4016111 TI - Deuterium NMR study of the effect of n-alkanol anesthetics on a model membrane system. AB - The effects of 25 mol% incorporation of two anesthetics, 1-octanol and 1-decanol, on a deuterated, saturated phospholipid in 50 wt% aqueous multilamellar dispersions have been studied by 2H-NMR spectroscopy and differential scanning calorimetry (DSC). The phospholipid used is sn-2 substituted '[2H31] palmitoylphosphatidylcholine' (PC-d31). DSC thermograms demonstrate that PC-d31 has phase behavior qualitatively similar to that of dipalmitoylphosphatidylcholine, with a pretransition at 31 degrees C and a main gel to liquid crystalline transition at 40 degrees C. Analysis of the temperature dependent 2H-NMR spectra in terms of the first moment, which is extremely sensitive to the phospholipid phase, shows that 1-octanol and 1-decanol depress and broaden the main transition. This is confirmed by DSC, which shows that the pretransition is eliminated by the 1-alkanols. The carbon-deuterium bond order of the phospholipid deuterated acyl chains, in the presence and absence of 1 alkanols, was determined from deuterium quadrupolar splittings. Spectra were analyzed using the depaking technique. A 1-alkanol concentration of 25 mol% had no significant effect on the profile of the carbon-deuterium bond order parameter SCD along the phospholipid acyl chain at 50 degrees C. Thus, it appears that the liquid crystalline phase is able to accommodate large amounts of linear anesthetic molecules without substantial effect on molecular ordering within the membrane bilayer. Preliminary results show that the transverse relaxation rates of the acyl chain segments are significantly decreased by the presence of 1 octanol or 1-decanol. PMID- 4016112 TI - Surprising thermal transition in fish myelin. AB - A new structural transition in nerve myelin has been discovered by means of X-ray diffraction of excised teleost nerves in physiological saline. The reversible transition is between two structures, designated AS and AL, with repeating distances (d spacings) differing by 25-35 A. When the temperature of bream spinal cord is lowered from room temperature to 4 degrees C, much but not all of the AS (short spacing) myelin changes into AL (long spacing) myelin. The change is reversed when the temperature is raised back to 22 degrees C, and it occurs a second time when the temperature is lowered again to 4 degrees C. The myelin in bream optic nerve undergoes a similar thermal transition, but the myelin in brachial plexus does not. The thermal transition does not involve the liquid crystal-to-gel transition observed in lipids and natural membranes. When a specimen is kept at constant temperature, there is a gradual conversion from AS to AL myelin which is not thermally reversible, suggesting the existence of two distinct subclasses of AL. Similarly, two subclasses are indicated for AS myelin since part of it does not transform thermally. The observations reported here may have significance for the evolutionary development of myelin. PMID- 4016113 TI - Calcium-dependence of sugar transport in rat small intestine. AB - The involvement of Ca2+ in the theophylline action on sugar transport was investigated in isolated rat small intestinal mucosa. Theophylline significantly increased cell water free sugar accumulation and reduced mucosal to serosal sugar fluxes both in the presence and absence of calcium, but the effects of theophylline were significantly less in calcium free media. In theophylline untreated tissues, calcium-deprived bathing solutions decreased tissue galactose accumulation and increased mucosal to serosal sugar flux. The calcium-channel blocker verapamil produced similar effects on intestinal galactose transport to those induced by low extracellular calcium activity. RMI 12330A and the calmodulin antagonist trifluoperazine abolished the theophylline-effects on intestinal galactose transport. Both drugs also affected sugar transport in basal conditions. These studies suggest that calcium might modulate sugar permeability across the basolateral boundary of rat enterocytes, and that its effect may be mediated by calmodulin. PMID- 4016114 TI - Propionate transport in rat liver cells. AB - Propionate extraction by liver is generally in the range of 95%, which could depend on a transport process across the cell membrane. The study reports conditions in which [14C]propionate uptake can be measured with minimal interferences from metabolism. Propionate uptake by isolated hepatocytes was mediated by two components: a low-affinity component of limited physiological interest and a high-affinity (apparent Km about 0.15 mM) component. This last component displayed a high capacity but was not Na+-dependent nor concentrative. Propionate transport was not markedly affected by acetate, butyrate or other C3 glucogenic compounds; it was inhibited by halogenated monocarboxylates, monochloroacetate and 2-chloropropionate being the most potent. Classical inhibitors of anion transport and of functional-SH groups were ineffective. Propionate uptake was responsive to external pH: stimulated by acidic and depressed by alkaline pH. Hepatic uptake of propionate in vivo was practically quantitative up to 0.8-1.0 mM in afferent plasma, in keeping with the measured capacity of the high-affinity component. It is suggested that propionate uptake is essentially carrier mediated but this process should not be rate limiting for hepatic utilization in physiological conditions. PMID- 4016115 TI - Ganglioside alterations in stimulated murine macrophages. AB - A two-dimensional thin-layer chromatographic technique has been used to separate and display gangliosides from murine peritoneal macrophages in different functional states. Resident macrophages have a relatively simple ganglioside pattern with about 15 resorcinol-positive spots. Gangliosides from resident cells contained mostly (90%) N-glycolylneuraminic acid. Thioglycolate-elicited and Corynebacterium parvum-activated macrophages have much more complex patterns with about 40 resorcinol-positive spots. Although ganglioside sialic acid content of stimulated macrophages was only slightly higher than that of resident cells, it consisted of nearly equal amounts of N-acetyl- and N-glycolylneuraminic acid. The shift in the ganglioside sialic acid type and the expression of different gangliosides in macrophages upon stimulation may help explain some of the differences in function and responsiveness noted in these macrophage populations. PMID- 4016116 TI - Calcium-mediated fusion to produce ultra large osmotically active mitochondrial inner membranes of controlled protein density. AB - We have developed a new membrane fusion method which produces ultra large, spherical mitochondrial inner membranes attached to microscope slides. The fused inner membranes measured up to 200 microns in diameter. The technique fuses native inner membranes as well as inner membranes in which the protein density has been varied by enriching with exogenous phospholipid. The fusion process is accomplished through the use of calcium, low pH and elevated temperature. Characterization of the fused membranes was carried out using phase, fluorescence, and freeze-fracture electron microscopy. These ultra large, fused inner membranes were found to model the inner membranes from which they were formed. The fused inner membranes were found to be osmotically active and are large enough for measuring the lateral diffusion of membrane components by fluorescence recovery after photobleaching and are large enough for microelectrode impalement. PMID- 4016117 TI - Bifunctional compound study of the active-centre location of cytochrome P-450 in a microsomal membrane ('float' molecules method). AB - A new approach, which we call 'float' molecules method for the determination of the active-centre location of cytochrome P-450 in a microsomal membrane, is proposed. We have synthesized new bifunctional compounds with the general formula: R-(CH2)n-S-CH2-CH(PO3H2)2, where n = 0,3,5,6,7,10 and R is a naphthalene containing radical. The compounds inhibit oxidation and binding of cytochrome P 450 substrates of type I (naphthalene, aminopyrine) and of type II (aniline). The inhibition is of a competitive character. Compounds (I-V) neither affect NADPH cytochrome c reductase, nor induce conversion of cytochrome P-450. A lipid soluble fluorescent probe (1,6-diphenyl-1,3,5-hexatriene) has been used to show that these compounds do not affect melting of microsomal membrane. The 31P-NMR method has demonstrated compound (III) to be incorporated into microsomal membrane so that the hydrophilic part is in the water phase. The data obtained make it possible to estimate the distance (r) between the membranes surface and Fe3+ in the active centre of the enzyme (r less than or equal to 20 A) under the assumption that all molecules of cytochrome P-450 are equally remote from the membrane surface. PMID- 4016118 TI - The accuracy of protein synthesis in reticulocyte and HeLa cell lysates. AB - The accuracy of translation in protein synthesis is measured as the rate of misincorporation of a particular amino acid, different from that specified by an mRNA codon, into protein. The cowpea variant of tobacco mosaic virus, CcTMV, contains no cysteine or methionine in its coat protein. Translation in vitro of purified CcTMV coat protein mRNA by rabbit reticulocyte and HeLa cell lysates has been performed. The coat protein product was purified by immunoprecipitation with specific antisera, and separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The error rate was measured by comparing the incorporation of [35S]cysteine with incorporation of [3H]leucine, and the total CcTMV coat protein synthesized was calculated from its known leucine content. An error rate of (1-2) X 10(-3) cysteines/CcTMV coat protein was obtained with reticulocyte lysates. If errors were cysteine incorporation in place of arginine, this number is converted to 3 X 10(-4) cysteine/codon. If cysteine was incorporated anywhere in the polypeptide, the rate is 9 X 10(-6) cysteines/amino acid. The error frequencies with HeLa cell lysates were 6-fold higher. Paromomycin, a eukaryotic misreading antibiotic, increased error rates 10-fold in both lysates. These data compare well with in vivo measurements and suggest that some transformed cells may survive with higher mistranslation rates. PMID- 4016119 TI - Condensation of the chromatin gel by cations. AB - Calf thymus chromatin gel, containing strongly bound nonhistone proteins, was used to study the effect of easily removable and tightly bound cations on the condensation of chromatin. The chromatin volume was found to be linearly dependent on the reciprocal square root of the concentration of easily removable cations (Tris X H+ + Na+ and Mg2+) except for the initial stages of condensation (up to 7-10 mM monovalent and 0.15-0.2 mM divalent cations). The effect of Mg2+ at the initial stage of condensation was not reproduced by Na+ and vice versa. At higher concentrations the effects of Na+ and Mg2+ were additive. The removal of tightly bound divalent cations by a treatment of the chromatin gel with 1,10 phenanthroline led to an approx. 50% increase in the volume of the chromatin gel, which was maintained at each concentration of easily removable cations. The 1,10 phenanthroline-caused decondensation of the chromatin gel was reversed by Ca2+ but not by Mg2+, Zn2+ and Cu2+. The chromatin gel pretreated with Ca2+ was not further decondensed by 1,10-phenanthroline. PMID- 4016120 TI - Messenger RNA turnover during bone marrow erythroid cell differentiation. AB - Incubation of bone marrow cells from anaemic rabbits in the presence of actinomycin D led to a decrease in total protein synthesis and an increase in the relative synthesis of globin. This increase in the proportion of globin was observed with in vivo labelling of cellular proteins and in vitro translation of isolated RNA, which indicates that the messenger RNA for globin is much more stable than the other bone marrow cell messages. This was further shown by pulse labelling the RNA and characterization of the different species by separation on a cDNA-oligo(dT)-cellulose column. Within 12 h after pulse-labelling the relative levels of globin mRNA had risen 10-fold, while a rapid decrease in the level of the poly(A)-rich RNA fraction was observed. Investigations into the mechanisms of this differential stability indicate that the more metabolically active cells from the early stages of erythropoietic development are more susceptible to inhibitors of RNA synthesis such as actinomycin D and alpha-amanitin. A preliminary study using a lysosomal inhibitor, chloroquine, indicates that there appear to be at least two degradative mechanisms, involving a lysosomal and a non lysosomal pathway, with selective specificity for different messages. PMID- 4016121 TI - The nuclear matrix continues DNA synthesis at in vivo replicational forks. AB - Alkaline cesium chloride gradient analysis of in vivo [3H]bromodeoxyuridine labeled and in vitro [alpha-32P]dCTP-labeled DNA was used to determine whether in vitro DNA synthesis in regenerating rat liver nuclei and nuclear matrices continued from sites of replication initiated in vivo. At least 70 and 50% of the products of total nuclear and matrix-bound in vitro DNA synthesis, respectively, were continuations of in vivo initiated replicational forks. The relationship of the in vitro DNA synthetic sites in total nuclei versus the nuclear matrix was examined by using [3H]bromodeoxyuridine triphosphate to density label in vitro synthesized DNA in isolated nuclei and [alpha-32P]dCTP to label DNA synthesized in isolated nuclear matrix. A minimum of about 40% of matrix-bound DNA synthesis continued from sites being used in vitro by isolated nuclei. Furthermore, nuclear matrices prepared from in vitro labeled nuclei were 5-fold enriched in DNA synthesized by the nuclei and were several-fold enriched, compared to total nuclear DNA, in a particularly high density labeled population of DNA molecules. PMID- 4016122 TI - Regulation of protein synthesis in eukaryotes. Eukaryotic initiation factor eIF-2 and eukaryotic recycling factor eRF from neuroblastoma cells. AB - eIF-2 purified from neuroblastoma cells consists of three subunits, which appear to be of molecular weight identical to those of the subunits of rabbit reticulocyte eIF-2. A protein fraction has been isolated from neuroblastoma cells with characteristics similar to eRF from reticulocytes: stimulation of amino acid incorporation in a hemin-deprived reticulocyte lysate, the removal of GDP from eIF-2-GDP complexes, a 4-5-fold stimulatory effect in a two-step reaction measuring 40 S preinitiation complex formation and a 3-3.5-fold stimulation in the methionyl-puromycin synthesis. In the methionyl-puromycin-synthesizing system phosphorylated eIF-2 is not responsive to the addition of this fraction from neuroblastoma cells. The protein fraction contains eRF which seems to be similar to the eRF isolated from Ehrlich ascites tumor cells and somewhat distinct from the reticulocyte factor. Incubation of neuroblastoma cell lysate in the presence of [gamma-32P]ATP results in the phosphorylation of a protein of Mr 36 000, migrating on SDS-polyacrylamide gels to the position of eIF-2 alpha. This protein is also phosphorylated in vitro by HRI from reticulocytes. These results may reflect a common underlying principle for the quantitative regulation of protein synthesis in eukaryotic cells. PMID- 4016123 TI - Neither adriamycin nor actinomycin D displaces Tb3+ from DNA. AB - The decay of fluorescence of Tb3+ bound to DNA was measured in the absence and presence of adriamycin and actinomycin D. The decay for Tb3+ bound to DNA was mainly exponential (lifetime: tau = 0.96 ms). In the presence of adriamycin or actinomycin D, the Tb3+ fluorescence decayed much faster, indicating that excitation energy was transferred from Tb3+ to the drugs. Extrapolation of the decay curves to zero time showed that the number of strongly emitting, DNA-bound terbium ions was not reduced by the presence of adriamycin or actinomycin D. Hence, these drugs do not seem to displace Tb3+ bound to DNA. PMID- 4016124 TI - Evidence against a temperature-dependent conformational change in urocanase from Pseudomonas putida. AB - Enzymatic activity of urocanase (4-imidazolone-5-propionate hydro-lyase, EC 4.2.1.49) has an unusual resistance to temperature changes, and a temperature dependent conformational change has been suggested (Hug, D.H. and Hunter, J.K. (1974) Biochemistry 13, 1427-1431). A conformational change or dissociation has been proposed in the range of 29-31 degrees C (Cohn, M.S., Lynch, M.C. and Phillips, A.T. (1975) Biochim. Biophys. Acta 377, 444-453). In this work, no evidence was found for a temperature-dependent conformational change or dissociation. Arrhenius plots of Km and Vmax were linear; the sedimentation coefficient was independent of temperature; tryptophanyl fluorescence was a linear function of temperature; and heat capacity calorimetry showed no transitions below 60 degrees C. PMID- 4016125 TI - Energy difference associated with proline isomerization in ribonuclease A. AB - We examined energy differences caused by the cis-trans transformation of every proline residues in the native structure of RNAase A. The results show that the cis form of Pro-93 and Pro-114 gave the lowest conformational energy, i.e., conformations after conversion of one of the proline residues to the trans form had a little higher energy; the transformation of Pro-42 and Pro-117 to the cis form, on the other hand, caused a much higher energy increase. PMID- 4016126 TI - Hamster hepatic cytochrome b5: purifications, immunochemical properties, and in vitro synthesis. AB - Cytochrome b5 has been purified from hamster liver microsomes. Both Ouchterlony double-diffusion and rocket immunoelectrophoresis experiments indicate that no immuno-cross-reactivity exists between guinea-pig anti-rabbit cytochrome b5 antibody and hamster cytochrome b5. However, anti-rabbit b5 IgG inhibited both hamster microsomal NADH-cytochrome c reductase and NADPH-dependent 7 ethoxycoumarin-O-deethylase activities. Hamster cytochrome b5 stimulated several reconstituted hamster cytochrome P-450-dependent monooxygenase activities and this stimulatory effect could be inhibited by antibody against rabbit cytochrome b5. Two-dimensional iodinated tryptic peptide mapping experiments provided evidence that the polypeptide fingerprint of hamster cytochrome b5 is substantially different from the fingerprints of cytochrome b5 isolated from rabbit, rat and bovine. We also studied the in vitro synthesis of hamster cytochrome b5 from liver mRNA using a wheat germ lysate system. A 16 kDa polypeptide, which is the same size as hamster cytochrome b5, was immunoprecipitated by antibody against rabbit b5. This experiment suggested that in vitro synthesized hamster cytochrome b5 is recognized by a heterologous antibody. Thus, hamster and rabbit cytochrome b5 do share some common immuno determinants which may be located close to the heme-binding active site. PMID- 4016127 TI - Solvent accessibility to flavin in oxynitrilase. AB - Oxynitrilase containing 2-thioFAD [C(2) = S] in place of FAD exhibits catalytic activity similar to that of native enzyme. Reaction of methyl methanethiolsulfonate with 2-thioFAD bound to oxynitrilase results in the formation of the corresponding flavin disulfide [C(2)-SSCH3]. Normal flavin [C(2) = O] is formed by reacting 2-thioFAD oxynitrilase with m-chloroperoxybenzoate or H2O2. Both reactions proceed via a spectrally detectable flavin 2-S-oxide intermediate [C(2) = S+-O-], but sizable amounts of this intermediate accumulate only in the m-chloroperoxybenzoate reaction (about 40%). While similar reactions have been reported with free 2-thioflavin, kinetic and other data indicate that the oxynitrilase reactions occur with intact enzyme. This shows that the 2 position of the pyrimidine ring in the bound coenzyme is accessible to solvent. The data are consistent with previous studies on the reaction of peroxides with oxynitrilase-bound 5-deazaFAD which show that the pyrimidine ring is accessible at position 4. Analogous studies indicate that the pyrimidine ring is buried in the case of flavin bound to lactate oxidase, since the data indicate that both positions 2 and 4 are inaccessible to solvent. PMID- 4016128 TI - Ultrasonic absorption in myoglobin and other globular proteins. AB - The ultrasonic absorption of myoglobin has been measured by the resonance and pulse-echo techniques as a function of pH. The absorption at a given frequency can be separated into pH-dependent and pH-independent contributions. Like other proteins, two peaks at pH 3 and 11.5 are observed which can be accounted for a proton-transfer reactions of the side-groups. In addition, the absorption undergoes a large increase within a small range of 0.2 pH unit at pH around 4, when denaturation of myoglobin occurs, indicating that the absorption is sensitive to the overall protein conformation. To elucidate the origin of the pH independent component, the absorptions of several other globular proteins at neutral pH are also measured. The absorptions of these proteins exhibit a linear correlation with their isothermal compressibilities, suggesting that the pH independent component is related to volume fluctuations of protein molecules. The activation energy of 4 kcal/mol found for this relaxation is consistent with such an interpretation. PMID- 4016129 TI - An essential tryptophan residue for rabbit muscle creatine kinase. AB - The tryptophan residues in rabbit muscle creatine kinase (ATP:creatine N phosphotransferase, EC 2.7.3.2) have been modified by dimethyl(2-hydroxy-5 nitrobenzyl) sulfonium bromide after reversible protection of the reactive SH groups. The modification of two tryptophan residues as measured by spectrophotometric titration leads to complete loss of enzymatic activity. Control experiments show that reversible protection of the reactive SH groups as S-sulfonates followed by reduction results in nearly quantitative recovery of enzyme activity. The presence of a 410 nm absorption maximum and the decrease in fluorescence of the modified enzyme indicate the modification of tryptophan residues. At the same time, SH determinations after reduction of the modified enzyme show that the reagent has not affected the protected SH groups. Quantitative treatment of the data (Tsou, C.-L. (1962) Sci. Sin. 11, 1535 1558) shows that among the tryptophan residues modified, one is essential for its catalytic activity. The presence of substrates partially protects the modification of tryptophan residues as well as the inactivation, suggesting that the essential tryptophan residue is situated at the active site of this enzyme. PMID- 4016130 TI - Kinetics of polymerization of hemoglobin S modified by thiol reagents and by oxidation. AB - The effects of four thiol reagents on the kinetics of polymerization of hemoglobin S have been studied in high phosphate buffer (1.8 M), in the presence (3 mM) or absence of sodium dithionite, depending on the reduction of mixed disulfides of Hb in the presence of this reducing agent. The effect of oxidized forms (methemoglobin) of HbS on the kinetics of aggregation of deoxyHbS was also studied because of the presence of 33% metHbS when HbS was modified by 4 aminophenyl disulfide. In the presence of sodium dithionite, the delay times prior to polymerization of deoxyHbS modified by N-ethylmaleimide, iodoacetamide and 4-aminophenyl disulfide were, respectively, 1.5-, 1.35- and 1.15-times longer than that of native deoxyHbS. The results indicate that the radicals bound to the cysteine beta 93 residue inhibit the contacts in the polymer formation to various extents but do not modify the size of the nuclei. PMID- 4016131 TI - Nanosecond transient resonance Raman spectra of the FeII-CO and FeIII-NO photolysis products of horseradish peroxidase. AB - Resonance Raman spectra, obtained with 7 ns pulsed laser excitation, are reported for the photoproducts of the FeII-CO and FeIII-NO adducts of horseradish peroxidase. The porphyrin skeletal frequencies are the same as those observed for unligated FeII and FeIII (native) horseradish peroxidase, respectively. The absence of unrelaxed spectra is discussed in relation to the photoproduct frequency shifts and relaxations observed previously for hemoglobin. It is proposed that protein conformational changes which are likely to be associated with the hydrogen-bonding interactions in the horseradish peroxidase heme pocket may not produce detectable changes in the porphyrin skeletal mode frequencies. PMID- 4016132 TI - Kinetics and mechanism of hemoglobin denaturation in alkali. AB - The denaturation of oxy, deoxy, CO and met derivatives of human hemoglobin A at pH 11.7 and 25 degrees C was followed by three assay methods: chromophore absorbance (which indicates changes in the heme), and the amount of precipitation in 24% ammonium sulfate neutral buffer or 0.1 M NaCl neutral buffer (which indicates degree of destabilization of the protein structure). We find that oxyhemoglobin denatures in two parallel reaction sequences. The rate of sequence I is increased when the sulfhydryl groups in the alpha 1 beta 1 subunit interface have been modified by binding p-hydroxymercuribenzoate (which forces monomer formation) and is decreased by the binding of -HgOH (which, unlike the sulfhydryls, is not ionized at pH 11.7). These results support a mechanism in which the net rate of monomer formation is rate limiting and is enhanced in alkali by the ionization of sulfhydryls in the alpha 1 beta 1 subunit interface. In subsequent rapid reactions, ferric hemoglobin and low-salt-precipitable protein are formed. The formation of an oxidant, such as superoxide, is indicated by the kinetics of sulfhydryl oxidation. The same oxidant would be available to initiate the second sequence by oxidizing some of the unreacted oxyhemoglobin to methemoglobin. During methemoglobin denaturation, as in sequence II, a low-salt soluble ferric hemochrome is formed. In both reactions, this intermediate becomes low-salt-precipitable at the same rate. Deoxyhemoglobin denatures to ferrous hemochrome at the same rate as oxyhemoglobin denaturation in sequence I, and provided oxygen is excluded, the denaturation is fully reversible on neutralization. In the absence of oxygen, CO-hemoglobin does not denature to any detectable extent. The destabilization of hemoglobin structure that was indicated by precipitability occurred only for ferriheme derivatives and was independent of disulfide formation. PMID- 4016133 TI - Isolation and glucose-6-phosphate-mediated dimerization of hexokinase from human heart. AB - Soluble hexokinase (ATP: D-hexose 6-phosphotransferase, EC 2.7.1.1) was purified from human heart. 1 kg of tissue provided 25 mg hexokinase with a specific activity of 58 units/mg, representing a 1700-fold purification and 47% yield. The purification involved six steps, including affinity chromatography with glucosamine attached to Sepharose. The material was homogeneous according to electrophoresis, gel-filtration and sedimentation in the ultracentrifuge, but gave two main components on electrophoresis in denaturing conditions. From determination of the sedimentation and diffusion coefficients, the relative molecular mass was calculated to be 105 000. The enzyme is monomeric, but glucose 6-phosphate promotes an association to dimers. This effect is reversible and is independent of the concentrations of glucose or inorganic phosphate. The results support the postulate that soluble and mitochondrion-bound hexokinases are identical. PMID- 4016134 TI - 4-Aminobutyrate aminotransferase. Conformational changes induced by reduction of pyridoxal 5-phosphate. AB - Conformational changes induced in 4-aminobutyrate aminotransferase (4 aminobutyrate:2-oxoglutarate aminotransferase, EC 2.6.1.19) by conversion of pyridoxal-5-P to pyridoxyl-5-P were examined by two independent methods. The reactivity of the SH groups of the reduced enzyme is increased by chemical modification of the cofactor. 1.8 SH per dimer of modified enzyme react with DTNB, whereas 1.2 SH per dimer of the native enzyme react with the attacking reagent under identical experimental conditions. The modified and native forms of the enzyme bind the fluorescent probe ANS, but the number of binding sites for ANS is increased as result of conversion of P-pyridoxal to P-pyridoxyl. After the conformational changes onset by reduction of the cofactor, the modified enzyme binds one molecule of pyridoxal-5-P with a Kd of 0.1 microM to become catalytically competent. The catalytic site of the reduce enzyme was probed with P-pyridoxal analogs. Like resolved 4-aminobutyrate aminotransferase, the reduced species recognize the phosphorothioate analog and regain 40% of the total enzymatic activity. Since the catalytic parameters of reduced and native 4 aminobutyrate aminotransferase are indistinguishable, it is concluded that the additional catalytic site of the reduced enzyme is functionally identical to that of the native enzyme. PMID- 4016135 TI - Identification of the milk fat globule membrane proteins. II. Isolation of major proteins from electrophoretic gels and comparison of their amino acid compositions. AB - The fat globule membranes of milk are derived from the apical plasma membrane of the mammary secretory cells. The nature of the membrane proteins, as isolated from cows' milk, has been studied by the use of discontinuous and continuous SDS gel electrophoresis. Six methods of preparation of milk fat globule membrane suggested by various authors were tested; gel electrophoresis showed that five major bands were present, independent of the method of preparation. The apparent molecular masses of these proteins as determined on SDS-gels (15% T) were 167, 142, 64, 49 and 46 kDa, respectively. The 167 kDa band stained only with periodic acid-Schiff reagent, while the 142 kDa band stained only with Coomassie blue; the last three bands stained with both. Delipidated membranes were extracted stepwise with water, 0.02 M NaCl and 0.6 M NaCl. The 64 kDa band appears to be nearly insoluble, while the bands of 142, 49 and 46 kDa are fractionated by this procedure. The resolution of all of these proteins by electrophoresis was superior to that achieved by molecular sieve chromatography, and so electrophoretic extraction was used to isolate the major proteins. Dansyl chloride derived proteins were used as markers. Amino acid compositions of the recovered proteins were obtained and are compared. PMID- 4016136 TI - Characterization of the siroheme active site in spinach nitrite reductase by resonance Raman spectroscopy. AB - The resonance Raman spectra of various species of spinach nitrite reductase (ferredoxin: nitrite oxidoreductase, EC 1.7.7.1) have been obtained with Soret excitation. These spectra allow for the vibrational properties of the unique siroheme chromophore at the enzyme's active site. The wholesale reordering of siroheme vibrational properties relative to those of protoporphyrins can be rationalized as resulting from a combination of symmetry lowering and bond order reductions within the siroheme macrocyle. PMID- 4016137 TI - Peptide synthesis catalyzed by the serine proteinases chymotrypsin and trypsin. AB - The ratio of the initial rates of aminolysis and hydrolysis in peptide semisynthesis catalyzed by chymotrypsin (EC 3.4.21.1) and trypsin (EC 3.4.21.4) was found to depend non-linearly on the concentration of the added nucleophile. This is in agreement with a mechanism for the peptide semisynthesis where nucleophile binding to the acyl-enzyme precedes the aminolysis reaction. The acyl enzyme-nucleophile complex can still be deacylated by water. A temperature optimum was observed for peptide synthesis for valinamide as nucleophile. This and the similarity of the P'1 specificity in peptide hydrolysis and nucleophile specificity in peptide semisynthesis also support the mechanism including the nucleophile binding. The influence of added nucleophiles on the acylation step during peptide synthesis was studied by determining kcat and Km for the appearance of the leaving group from the acyl donor. Acceptor (= nucleophile) specificity was shown to be more important for high ratios of aminolysis: hydrolysis than donor specificity. The maximum product concentration during kinetically controlled peptide semisynthesis was found to be independent of the enzyme content. PMID- 4016138 TI - Glycosylated kappa-caseins and the sizes of bovine casein micelles. Analysis of the different forms of kappa-casein. AB - Fast protein liquid chromatography (FPLC) of the kappa-casein from bovine casein micelles of different sizes is used to demonstrate that the proportions of glycosylated and non-glycosylated forms of kappa-casein do not vary with micellar size. The results suggest that glycosylated kappa-casein is distributed similarly to unglycosylated kappa-casein within the micellar structure. PMID- 4016139 TI - Occurrence of N-acylethanolamine phospholipids in fish brain and spinal cord. AB - N-Acylethanolamine phospholipids were identified in the central nervous system of the fresh water fish, pike (Esox lucius) and carp (Cyprinus carpio), at levels ranging from 0.1 to 0.9% of total phospholipid. The N-acylethanolamine phospholipids of carp brain were isolated and characterized by chemical, biochemical and spectroscopic methods. Two major species, 1,2-diacyl-sn-glycero-3 phospho(N-acyl)ethanolamines (approx. 30%) and 1-O-(1'-alkenyl)-2-acyl-sn-glycero 3-phospho(N-acyl)ethanolamines (approx. 70%) were identified. The N-acyl groups of each species consisted primarily of 16:0 (approx. 60%) but also contained 16:1, 18:0 and 18:1 (approx. 10% each) and a number of trace constituents. The N acylethanolamine phospholipids had O-acyl and O-alkenyl group compositions similar but not identical to those of the ethanolamine phospholipids of the same tissue. N-Acylethanolamine phospholipids were present in all subcellular fractions of carp brain, except mitochondria. PMID- 4016140 TI - Effect of dietary cholesterol on erythrocyte peroxidant stress in vitro and in vivo. AB - The effect of dietary variation of plasma cholesterol concentrations on the susceptibility of erythrocytes to in vitro and in vivo peroxidant stress was studied in rats. Malonyldialdehyde, produced in vivo (endogenous malonyldialdehyde) or following in vitro exposure of cells to 10 mM H2O2 (H2O2 malonyldialdehyde), was used as a measure of peroxidant stress. After 5 weeks, the plasma cholesterol concentrations in rats receiving 1.2% cholesterol + 0.6% cholic acid in their diet rose to 6-times that of control rats receiving a diet without added cholesterol; at the same time, erythrocyte H2O2 malonyldialdehyde in the cholesterol-fed rats decreased significantly relative to the control rats. During subsequent exposure of both groups to in vivo peroxidant stress with phenylhydrazine in two separate dose trials, erythrocyte peroxidant stress remained significantly lower in the cholesterol-fed rats: at a dose of 100 mumol/100 g body weight, H2O2 malonyldialdehyde was lower; at a dose of 25 mumol/100 g body weight, both endogenous and H2O2 malonyldialdehyde were lower. Erythrocyte membrane cholesterol concentrations were 12% higher in the cholesterol-fed rats than in controls. The effects of in vivo peroxidant stress on plasma cholesterol were also studied. In vivo peroxidant stress at the higher dose of phenylhydrazine produced a decrease in plasma cholesterol concentrations of control rats. The lower dose had no effect on this group and the plasma cholesterol concentrations were unchanged in the cholesterol-fed rats during both treatments. The data suggest that elevated plasma cholesterol concentrations are protective against erythrocyte peroxidant stress. The mechanism of cholesterol's protective effect is probably mediated through elevated membrane cholesterol concentrations. PMID- 4016141 TI - Effects of antimalarial drugs on phospholipase A and lysophospholipase activities in plasma membrane, mitochondrial, microsomal and cytosolic subcellular fractions of rat liver. AB - Activities of membrane-associated phospholipases A1 and A2, and membrane associated as well as soluble lysophospholipases were measured in different subcellular fractions of rat liver, using suspensions of stereospecifically labelled radioactive phospholipids as substrates. Plasma membranes and endoplasmic reticulum were shown to contain phospholipase A1 and lysophospholipase activities, both of which could be stimulated by Ca2+, mitochondria Ca2+-dependent phospholipase A2 and cytosol Ca2+-independent lysophospholipase activities. Each of these lipolytic enzymes could be inhibited by antimalarial drugs (chloroquine, mepacrine, primaquine) at concentrations above 1 x 10(-4) M. Inhibition of the alkaline cytosolic lysophospholipase by these drugs was noncompetitive with respect to the substrate, and the inhibitory potency increased, when the pH was raised. PMID- 4016142 TI - Activation of nonspecific lipase (EC 3.1.1.-) by bile salts. AB - The enzyme nonspecific lipase (EC 3.1.1.-) from rat pancreas has been isolated and its amino acid composition determined. The amino acid composition confirms more indirect evidence that nonspecific lipase is not the same enzyme as cholesteryl ester hydrolase. Activation of the enzymatic activity by bile salts has been studied by equilibrium dialysis, gel filtration, light scattering, circular dichroism and fluorescence polarization. The binding of bile salt by the enzyme is saturable and is associated with a conformational change. Upon binding cholate, the protein experiences a decrease in beta-structure with no significant change in alpha-helix content, an increase in apparent Stokes radius, a decrease in light scattering properties, and a slight decrease in polarization of the intrinsic tryptophan fluorescence. Attachment of bile salt is associated with decreased reactivity of essential sulfhydryl groups, but no detectable change in reactivity of amino groups. A change to a more nearly spherical shape upon binding bile salt would be consistent with the experimental observations, but the exact sites of binding remain uncertain. PMID- 4016143 TI - Characterization of the platelet aggregation inducer and inhibitor from Echis carinatus snake venom. AB - Echis carinatus venom was separated into twenty fractions by means of ultrafiltration and CM-Sephadex C-50 column chromatography. Fraction II possessed inhibitory activity on the aggregation of washed rabbit platelets and fraction XII possessed the procoagulant and platelet aggregation-inducing activity. Both were further purified by gel filtration on a Sephacryl S-200 column. The purified aggregation inducer was a glycoprotein with procoagulant activity 10-12-times that of the crude venom. It possessed proteinase and amidase but was devoid of esterase activity. The molecular weight was 16 000, and it contained 8.7% of neutral sugar. The isoelectric point was pH 7.6. The purified aggregation inhibitor was a single peptide chain with a molecular weight of 6800 and contained 22.1% of neutral sugar. The isoelectric point was pH 4.8. It was devoid of any enzymatic activity of the crude venom. The IC50 was about 10 micrograms/ml on the thrombin-induced platelet aggregation. The inhibitory activity was fully retained after the treatment of the venom aggregation inhibitor with neuraminidase, but was completely destroyed by sodium metaperiodate. Upon heat treatment at 90 degrees C, the venom aggregation inhibitor was heat stable at pH 5.5 for 4 h, but was completely destroyed after 2 h at pH 8.9 and retained about 50% of its inhibitory activity of the control at pH 7.2 for 4 h. The venom aggregation inhibitor decreased the elasticity of the whole blood clot, and this effect was related to its inhibitory action on platelet aggregation instead of blood coagulation. PMID- 4016144 TI - Purification and partial characterization of rat kidney histamine-N methyltransferase. AB - Histamine-N-methyltransferase (EC 2.1.1.8) was purified 1700-fold with a yield of 9% from rat kidney. Purification included ammonium sulfate precipitation, linear gradient DEAE-cellulose chromatography and S-adenosylhomocysteine affinity chromatography. The purified enzyme preparation showed a single protein band in sodium dodecyl sulfate-polyacrylamide gel electrophoresis with a molecular weight of 35000. The isoelectric point of the enzyme was at pH 5.2. The purified enzyme preparation did not contain detectable amounts of histamine. The purified enzyme was totally inhibited in 100 microM parahydroxymercuric benzoate and in 10 microM iodoacetamide, and it was found to be stabilized with dithiothreitol (1 mM), suggesting that the enzyme has an SH-group in the active center. The Km values for histamine and S-adenosylmethionine were 6.0 and 7.1 microM, respectively. 50% inhibition of histamine-N-methyltransferase was obtained at 28 microM S adenosylhomocysteine and 100 microM methylhistamine. The purified enzyme was slightly inhibited in 1 mM methylthioadenosine. Histamine in concentrations higher than 25 microM caused substrate inhibition. PMID- 4016145 TI - Characterization of a 22 kDa protein with widespread tissue distribution but which is uniquely present in secretions of the testis and epididymis and on the surface of spermatozoa. AB - The purification is reported of a 22 kDa protein which was first identified as one of the major components of the luminal secretion of the rat testis and epididymis. Antibodies against the 22 kDa protein cross-reacted with a protein of the same molecular weight in cytosolic extracts of other tissues from both male and female rats. However, since the protein could not be detected in blood, peritoneal fluid, saliva, milk, uterine fluid, seminal vesicle secretion, coagulating gland secretion or prostatic secretion, it would appear that the testis and epididymis may be unique in containing the protein in a soluble form within their luminal secretions. Proteins with slightly lower molecular weight were detected by the antibodies in cytosolic extracts of tissues from other animals (mice, rabbits, sheep, pigs, cattle), indicating that the protein may be conserved in a variety of species. However, in contrast to the rat, the protein was apparently not present in the testicular and epididymal secretions of these species. In addition to the occurrence of the 22 kDa protein as a soluble moiety in rat testicular and epididymal fluids, the protein was also located on sperm plasma membranes where its distribution was restricted to the surface of the flagellum. Amongst sperm surface proteins, the 22 kDa protein was the major protein containing sulphydryl groups and one of the major entities containing disulphide bonds. These properties may be of importance in the maintenance of sperm viability. PMID- 4016146 TI - Highly sulfated proteochondroitin sulfates synthesized in vitro by rat glomeruli. AB - A previous report from this laboratory (Kobayashi, S., Oguri, K., Kobayashi, K. and Okayama, M. (1983) J. Biol. Chem. 258, 12051-12057) indicated that isolated rat glomeruli synthesized three species of sulfated glycoconjugates in vitro, namely, sulfated glycoproteins, proteoheparan sulfates and proteochondroitin sulfates. In the present study, the proteochondroitin sulfates, which showed the greatest incorporation of [35S]sulfate among the three sulfated glycoconjugates, were isolated and characterized. Radiolabeled tissue proteochondroitin sulfates were clearly separated on Sepharose CL-6B into three components with partition coefficients (Kd) of 0.16, 0.22 and 0.58, and medium proteochondroitin sulfates were separated into two components with Kd values of 0.33 and 0.62. When the chondroitin sulfate chains released by alkaline borohydride treatment were analyzed by digestion with chondroitinase AC-II, chondroitinase ABC, chondro-6 sulfatase and chondro-4-sulfatase, the results showed that all the samples contained glucuronosyl-N-acetylgalactosamine (chondroitinase AC-II-susceptible sequences, 72-86%) and iduronosyl-N-acetylgalactosamine (chondroitinase ABC susceptible sequences, 14-28%), containing 4-sulfated N-acetylgalactosamine (50 70%) and 4,6-disulfated N-acetylgalactosamine (30-50%). On two-dimensional electrophoresis on cellulose acetate, all samples gave a single spot which closely coincided with chondroitin sulfate E of squid cartilage in electrophoretic mobility. These results indicated that the chains were highly sulfated chondroitin sulfates containing glucuronic acid and iduronic acid residues. PMID- 4016147 TI - Effect of sulfite on the energy metabolism of mammalian tissues in correlation to sulfite oxidase activity. AB - Mammalian tissues show significant differences in the activity of sulfite oxidase (EC 1.8.3.1) which detoxifies sulfite by oxidation to sulfate. Lung tissue and phagocytic cells such as alveolar macrophages, peritoneal macrophages, Kupffer cells and granulocytes show very low activities of sulfite oxidase. Liver tissue and hepatocytes, however, exhibit high activities of sulfite oxidase. Lung tissue and macrophages show an almost 100% decrease of the intracellular ATP levels when incubated with 1 mM sulfite at pH 6 for 30 min. In addition, the O2 consumption of lung tissue is inhibited by 1 mM sulfite at pH 6 by more than 80%. This sulfite-induced decrease of the ATP level and of the O2 consumption of lung tissue is enhanced between pH 6.0 and pH 7.4 with decreasing pH value of the incubation medium. In contrast, the ATP levels in liver tissue and hepatocytes are not affected by 1 mM sulfite at pH 6. The O2 consumption of liver tissue and hepatocytes is significantly increased by sulfite due to the high activities of sulfite oxidase. Therefore, the activity of the 'sulfite-detoxifying enzyme' sulfite oxidase and the sensitivity of the energy metabolism to sulfite show a reciprocal relationship in the tissues and cells studied. PMID- 4016148 TI - Placental formation of lactate from transferred L-alanine and its impairment by aminooxyacetate in the late-pregnant rat. AB - After 20 min infusion of L-[U-14C]alanine through the left uterine artery in 21 day-pregnant rats, the radioactivity in the plasma of fetuses from the left uterine horn was much higher than in their mothers and was composed of approximately equal parts of [14C]alanine and [14C]lactate, with a minor percentage of [14C]glucose. Radioactivity in fetal plasma was much lower when the mothers were infused with alpha-amino[14C]isobutyric acid. The simultaneous infusion of aminooxyacetate decreased materno-fetal transfer of radioactivity from [14C]alanine but not from alpha-amino[14C]isobutyric acid, and this effect corresponded to a complete disappearance of the [14C]lactate in fetal plasma without affecting [14C]alanine levels or alanine concentration in the fetuses. Placenta slices in vitro metabolized L-[U-14C]alanine into [14C]lactate and 14CO2 at the rate of 7 nmol/g per min, and this process was inhibited by the presence of 1 mM aminooxyacetate in the medium. Placental uptake of alpha amino[14C]isobutyric acid was half that of [U-14C]alanine, and aminooxyacetate did not affect this parameter with either of the labelled compounds. Results indicate that the lower transfer to the rat fetus of the 14C atoms from alpha amino[14C]isobutyric acid as compared to that from [14C]alanine is due not only to the diminished placental carrier system of the former but also to its non metabolyzable condition. It is proposed that the capacity of the placenta to metabolyze L-alanine to lactate and the subsequent release of lactate to the fetus constitute important factors for the fetal metabolic economy. PMID- 4016149 TI - 5'-Iodothyronine deiodinase of rat liver: activity in microsomes prepared by various methods, solubilization by detergents and partial purification. AB - Iodothyronine deiodinase activities of rat liver microsomes prepared by (1) differential centrifugation, (2) column chromatography, (3) precipitation with Ca2+, (4) precipitation at low pH, or combinations of these were compared. Method 2 or 2 followed by 4 provided microsomes with specific activities 4.6- and 7.4 times higher than method 1, respectively. Both Triton X-100 at 0.1% (w/v) and 3 [(3-cholamidopropyl)dimethylammonio]-1-propane sulfonate (Chaps) at 4-6 mM efficiently solubilized deiodinase and were not inhibitory at low concentrations. The Chaps-soluble enzyme could be moderately purified by fractionation with ammonium sulfate but more effectively with poly(ethylene glycol). PMID- 4016150 TI - Reduction of 7-ketolithocholic acid to chenodeoxycholic acid by rat liver preparations in vitro. AB - The formation of chenodeoxycholic acid via 7-ketolithocholic acid by rat liver preparations was examined in vitro. Results showed that a rat liver preparation reduced 7-ketolithocholic acid mainly to chenodeoxycholic acid and to ursodeoxycholic acid in a smaller amount, and that the reductase required NADPH but not NADH as coenzyme and was mainly localized in the microsomes. PMID- 4016151 TI - Altered membrane association of glycogen phosphorylase in the dystrophic chicken. AB - The subcellular distribution of glycogen phosphorylase in pectoralis muscle from normal and dystrophic chickens was determined as a function of age. A substantially larger proportion of the total activity was associated with membranous cellular organelles, both mitochondria and sarcoplasmic reticulum, in preparations from dystrophic birds. The difference could be detected as early as 2 weeks ex ovo. Interaction of phosphorylase with cellular membranes may provide a probe for the underlying membrane defect in this dystrophy model. PMID- 4016152 TI - The assimilation of tri- and tetrapeptides by human erythrocytes. AB - Evidence is presented that tripeptides enter human erythrocytes via saturable transport system(s) at rates similar to those previously described for dipeptides (King, G.F. and Kuchel, P.W. (1985) Biochem. J. 227, 833-842) but that the transmembrane flux rates for tetrapeptides are considerably less. 1H spin-echo NMR spectroscopy was used to monitor the coupled uptake and hydrolysis of peptides by red cells, since it enabled the simultaneous measurement of the levels of substrates and products of peptidase-catalysed reactions in suspensions with haematocrits similar to those found in vivo. Weighted non-linear least squares regression of the integrated Michaelis-Menten equation onto progress curves obtained from the hydrolysis of Tyr-Gly-Gly and Gly-Gly-Gly in RBC lysates gave Km = 2.11 +/- 0.08 and 23.4 +/- 0.9 mmol/l and Vmax = 307 +/- 3 and 905 +/- 22 mmol/h per 1 packed cells, respectively. In whole cell suspensions, the rate of hydrolysis was considerably less and was dominated by the transmembrane flux of tripeptide. Progress curve analysis thus yielded the steady-state kinetic parameters for peptide transport; the values were Km = 11.6 +/- 1.1 and 56 +/- 18 mmol/l and Vmax = 12.9 +/- 3.0 and 36.4 +/- 3.2 mmol/h per 1 packed cells, respectively, for the previously mentioned peptides. The rate of transport of the tetrapeptide Gly-Gly-Gly-Gly was considerably less than either of the tripeptides. The above mentioned steady-state kinetic parameters were used in computer simulations of the coupled uptake and hydrolysis of tripeptides by human erythrocytes under physiological conditions; these simulations revealed certain similarities between the rates of peptide uptake by erythrocytes and the intestine in vivo. PMID- 4016153 TI - Specific neutralizing antiserum against a polypeptide growth inhibitor for mammary cells purified from bovine mammary gland. AB - A recently published method for purification of a new inhibitor of growth of mammary cells in vitro from bovine mammary gland has been modified to yield several hundred micrograms of inhibitor per kg of glandular tissue. The inhibitory effect exerted by this preparation to Ehrlich ascites mammary carcinoma cells fulfilled all biological criteria of specificity established earlier for preparations obtained by other means, the most important being that the inhibitory effect is abolished by the epidermal growth factor and insulin. The preparation is shown to consist mainly of a protein of 13 kDa which appears to be not glycosylated. An antiserum raised in mice against the inhibitor is demonstrated to be specific for the 13 kDa bovine mammary gland protein. Neutralization of the inhibitory activity by the specific antiserum strongly supports the view that the 13 kDa protein is indeed the carrier of inhibitory activity. First data on tissue distribution obtained with an enzyme-linked immunosorbent assay revealed a high concentration of the anti-inhibitor-antiserum reactive antigen in bovine lactating but not in non-lactating mammary gland tissue and in milk fat globule membranes. Some reactivity was also found in bovine lung. These data are interpreted with respect to a possible physiological significance of the growth inhibitor. PMID- 4016154 TI - A comparison of in vivo catalysis by creatine kinase in avian skeletal muscles with different fibre composition. AB - The maximum activity of creatine kinase in vitro is similar in the pectoralis major muscle of the chicken and the duck. However, the flux (phosphocreatine to ATP) as measured by 31P saturation transfer NMR in vivo is almost 2-fold higher in the duck. This apparent discrepancy can be accounted for by the differences in the cytosolic free ADP concentrations in resting muscle. PMID- 4016155 TI - The synthesis and esterification of cholesterol by hepatocytes and H35 hepatoma cells are independent of the level of nonspecific lipid transfer protein. AB - The level of the nonspecific lipid transfer protein (i.e., sterol carrier protein 2) is 16-fold lower in the Reuber H35 hepatoma cells as compared to the hepatocytes in culture (49 and 810 ng of protein per mg of 105000 X g supernatant protein, respectively). In order to establish whether there is a relationship between the level of nonspecific transfer protein and intracellular cholesterol metabolism, we have determined the biosynthesis and esterification of cholesterol in these hepatoma cells and hepatocytes. Both types of cells incorporated [3H]mevalonate into cholesterol and cholesterol ester. Incubation of both cell types with [3H]cholesterol in the medium resulted in a time-dependent uptake and subsequent conversion into cholesterol ester. In both instances, the amount of 3H label incorporated into cholesterol per mg of cellular protein was about 2-fold higher for the hepatoma cells. The kinetics of esterification of endogenously synthesized cholesterol were similar for both hepatoma cells and hepatocytes. Esterification of cholesterol derived from the medium proceeded 2-times faster in the hepatoma cells than in the hepatocytes. From the kinetics of cholesterol esterification we conclude that cells do not discriminate between cholesterol synthesized de novo and cholesterol derived from the medium. In addition, the proposition that the nonspecific lipid transfer protein is involved in cholesterol synthesis and esterification is not substantiated by this study. PMID- 4016156 TI - Accumulation of N-acetylneuraminic acid (sialic acid) in human fibroblasts cultured in the presence of N-acetylmannosamine. AB - Human skin fibroblasts incubated for 72 h in medium containing 10 mM N-acetyl-D mannosamine accumulate material that yields a chromophore in the presence of thiobarbituric acid. This material was tentatively identified as free (unbound) sialic acid due to its reactivity with thiobarbituric acid prior to acid hydrolysis, its solubility in 10% trichloroacetic acid, its chromatographic properties on an anion-exchange column and its enzymatic susceptibility to acylneuraminate pyruvate-lyase. Mass spectrometry analysis established that the accumulated material was, in fact, N-acetylneuraminic acid. Loading studies demonstrated a linear relationship between the amount of N-acetylmannosamine in the medium and the level of sialic acid accumulating within the cells. Cells grown in the absence of N-acetylmannosamine contained an average of 5 nmol free sialic acid/mg protein, while cells cultured for 72 h in 20 mM amounts of this material contained an average of 156.3 nmol free sialic acid/mg protein. When the cells were removed from the N-acetylmannosamine-enriched medium and incubated in regular medium, more than 80% of the accumulated, intracellular sialic acid disappeared within the first 96 h. It was concluded from these data that normal fibroblasts cultured in medium enriched with N-acetylmannosamine store large amounts of N-acetylneuraminic acid and can thus serve as an excellent model for the study of both normal and abnormal sialic acid metabolism, transport, storage and/or metabolic (feedback) regulation in human tissue. PMID- 4016157 TI - A study of the kinetics and mechanism of ADP-triggered platelet aggregation. AB - The time-course of ADP-triggered aggregation of human blood platelets has been followed by sensitive right-angle light scattering intensity measurements as a function of the platelet and fibrinogen concentrations. Rayleigh-Gans light scattering theory has been combined with the Smoluchowski aggregation model to predict the dependence of the right-angle scattering intensity on particle size and concentration as well as the time-dependent changes during aggregation. The validity of the calculations was confirmed by measuring the scattering intensity with suspensions of polystyrene microspheres of known radius, as well as the time dependent changes in the 90 degrees scattering intensity during aggregation of these particles. However, in contrast to the predictions of the model, the time course of the scattering intensity changes during platelet aggregation was characterized by single exponential decay with a rate constant which reached a limiting value of 0.017 s-1 at high platelet concentrations. The value of kagg was also independent of the fibrinogen concentration over a 30-fold range. Covalently cross-linked fibrinogen dimers and Fragment D-inhibited fibrin protofibrils yielded aggregation rates that agreed with those measured with fibrinogen. The results indicate that the rate of platelet aggregation is not limited by either the rate of fibrinogen binding or the frequency of platelet platelet collisions under these conditions. PMID- 4016158 TI - Liposome uptake by cultured macrophages mediated by modified low-density lipoproteins. AB - We have investigated effects of native low-density lipoproteins (LDL) and malondialdehyde-treated LDL on the interaction of 5(6)-carboxyfluorescein-labeled liposomes bearing antibodies to LDL with cultured J774 macrophages. It was found that an addition of modified LDL to the incubation medium resulted in 15-20-fold increase of carboxyfluorescein binding to cells, whereas native LDL did not produce such effect. The increase of carboxyfluorescein binding to macrophages in the presence of modified LDL was not due to an enhanced leakage of the label from liposomes. The modified-LDL-mediated binding of carboxyfluorescein to cells was reduced to 20-30% of the initial level in the presence of cell-respiration inhibitors (NaF and antimycin A). Fluorescent microscopy data also indicate the modified-LDL-induced incorporation of liposome contents into cells. The results obtained in this study make it possible to assume that in the presence of malondialdehyde-treated LDL, liposomes with antibodies to LDL may be incorporated into macrophages via the receptor-mediated pathway for modified LDL. PMID- 4016159 TI - Multiplication and refractoriness in the cat's retinal-ganglion-cell discharge at low light levels. AB - Measurements of the pulse-interval distribution and pulse-number distribution for cat retinal ganglion cells in darkness and light have been carried out by Barlow, Levick, and Yoon. The experimental results for an on-center brisk-sustained cell are in accord with a mathematical model incorporating four features: Poisson quantum fluctuations, additive dark noise, multiplication noise (random multiple neural spikes per absorbed quantum), and refractoriness. The data cannot be properly explained by a model lacking any one of these features. Parameters extracted from the model are in good agreement with physiological values. PMID- 4016160 TI - Asymmetric lightness cancellation in Craik-O'Brien patterns of negative and positive contrast. AB - The Craik-O'Brien illusion was measured for patterns of negative and positive contrast by a compensation method. The illusion of negative contrast (black teeth on uniform field) was stronger than that of positive one (white teeth). The amount of compensation increased linearly with increasing tooth width, but was nonlinear, showing two phases with increasing tooth height. The results might be explained by the concept of the antagonistic and nonantagonistic mechanisms in the lower stage of the visual system, and the reconstructive process of the barrier activity against the lateral spread in the higher stage. PMID- 4016161 TI - Identification and estimation algorithm for stochastic neural system. II. AB - The algorithm for identifying the stochastic neural system and estimating the system process which reflects the dynamics of the neural network are presented in this paper. The analogous algorithm has been proposed in our preceding paper (Nakao et al., 1984), which was based on the randomly missed observations of a system process only. Since the previous algorithm mentioned above was subject to an unfavorable effect of consecutively missed observations, to reduce such an effect the algorithm proposed here is designed additionally to observe an intensity process in a neural spike train as the information for the estimation. The algorithm is constructed with the extended Kalman filters because it is naturally expected that a nonlinear and time variant structure is necessary for the filters to realize the observation of an intensity process by means of mapping from a system process to an intensity process. The performance of the algorithm is examined by applying it to some artificial neural systems and also to cat's visual nervous systems. The results in these applications are thought to prove the effectiveness of the algorithm proposed here and its superiority to the algorithm proposed previously. PMID- 4016162 TI - Pacemaker neuron model with plastic firing rate: entrainment and learning ranges. AB - The model proposed puts forward a hypothesis on how some pacemaker neurons learn to fire at the frequency imposed by the stimulation. It builds on previous developments in two separate research fields: neural modelling and neuronal learning theory, providing an electrophysiological model of neuronal learning. Simulation results are shown to be in qualitative agreement with experimental data reported for Aplysia and crayfish. The analytical study of the PRC reveals that the postulated learning rule tends to favour the emergence of simple entrainment ratios. The model is worth consideration not only because of its autonomous functioning, described in this paper, but also because it constitutes a suitable building-block for a net aimed at reproducing the temporal-pattern learning phenomena shown by some neural structures. PMID- 4016163 TI - Detection of binocular disparities. AB - A stereo correspondence algorithm designed to perform matching on figurally similar images (arising in normal human binocular vision) is described. It is based on the observation that the operational principles underlying biological stereo disparity detection seem to be extremely general and few in number instead of an extended set of specific "constraints". We identify one general characteristic of objects in the three dimensional world and use it to formulate a simple noniterative, parallel and local algorithm that successfully detects disparities generated by opaque as well as transparent surfaces. PMID- 4016164 TI - Saccade-related brain potentials in semantic categorization tasks. AB - Saccade-related brain potentials (SRPs) were recorded in word categorization tasks in which subjects had to perform a saccade in order to perceive the stimulus. For all three conditions representing different degrees of complexity of semantic categorization, the stimuli belonged to one of two categories which appeared with the respective probabilities of either 0.20 or 0.80. The late positivity (P4) of the SRPs to infrequent stimuli appeared systematically later as the complexity of stimulus evaluation increased: The easiest categorization was accompanied by a P4 at 400 msec, in the more complex condition it peaked at 600 msec, and in the most difficult semantic categorization the P4 peaked even later, at 680 msec. This shift in peak latency with increasing complexity of categorization is in agreement with the results for traditional ERPs (e.g. Kutas and Donchin, 1978). The possible overlap of the late components was investigated by applying Principal Component-Varimax Analysis to the SRPs. PMID- 4016165 TI - Abstracts of papers presented at the eleventh annual scientific meeting of the Psychophysiology Society. London, December 1983. PMID- 4016166 TI - Fetal distribution of styrene in rats after vapor phase exposures. AB - Pregnant rats were subjected to a 5-hour exposure of either 2,000 or 1,000 ppm atmospheres of styrene. Concentrations of styrene in the maternal blood and in each fetus were measured. The fetal concentrations in the 2,000 ppm exposure group were significantly more than double that in the 1,000 ppm group. Fetal weight and distribution of styrene appear to be related to the fetal position on the uterine horn. Those at the ovarian and cervical ends of the uterine horn were of lowest weight and those at the ovarian end had the highest concentration of styrene. Concentrations of styrene appeared to be much lower in the fetuses than in maternal organs and tissues after similar exposures. PMID- 4016167 TI - Influence of bromocriptine on plasma prolactin, human placental lactogen, beta HCG and steroid hormones in early human pregnancy. AB - To study the role of prolactin in the regulation of the production of 17 beta oestradiol, HPL, beta-HCG, progesterone, testosterone, delta 4-androstenedione and 5 alpha-dihydrotestosterone, 20 healthy women were given 5 mg of bromocriptine daily for two weeks between 7-9 weeks of normal pregnancy. Plasma HPRL, HPL, HCG, oestradiol, progesterone, testosterone, delta 4-androstenedione and 5 alpha-dihydrotestosterone levels were measured before and one and two weeks after the start of bromocriptine-application, and they were compared with those examined in control groups (18 women). Bromocriptine induced a significant HPRL depression at one week and two weeks. Other hormones, except progesterone, showed no significant differences between two groups. These data suggest that neither maternal hypoprolactinemia nor bromocriptine during normal early human pregnancy interfere with the normal synthesis of sex steroids. PMID- 4016168 TI - The fetal distribution of some aliphatic chlorinated hydrocarbons in the rat after vapor phase exposure. AB - Rats, on the 17th day of pregnancy, were exposed for five h to several different concentrations, ranging from about 100 to 3,000 ppm, of methylene chloride, 1,2 dichloroethane, chloroform and trichloroethylene. Immediately following exposure, the concentrations of these compounds were determined in each fetus and in the maternal blood and characterized as a function of the administered dose. Fetal weights and fetal concentrations were related to their position on the two horns of the uterus. Fetal weight distribution conformed with observations previously reported [Withey and Karpinski 1983, Barr et al. 1969]. Fetuses at either end of each branch of the uterine horns had the lowest concentration of trichloroethylene. The data for methylene chloride and dichloroethane revealed a linear decrease in fetal concentration with the location of the fetus from the ovarian to the cervical end of the uterine horns. These relationships were consistent across doses. Fetal chloroform concentrations did not appear to be related to fetal position. Good linear relationships between the mean fetal concentrations and the maternal blood concentrations with exposure level were observed for the four compounds used in this study. PMID- 4016169 TI - Human placental aromatase activity: use of a C18 reversed-phase cartridge for separation of tritiated water or steroid metabolites in placentas from both smoking and non-smoking mothers in vitro. AB - Commercial reversed-phase cartridges were used for the separation of 3H2O which was produced in an aromatization reaction of androstenedione by human placenta in vitro. The assay is simple, rapid and reproducible. Metabolites originating from androstenedione were separated and quantified by thin layer chromatography. The microsomal fraction exhibited the highest aromatase activity which was inhibited (54%) by aminoglutethimide (500 microM) and by about 30% by alpha-naphthoflavone. Aromatase activity was not inhibited by known inhibitors of xenobiotic metabolism such as metyrapone or SKF 525A or by xenobiotic substrates such as 7 ethoxycoumarin or benzo(a)pyrene. Placental aromatase activity was not affected by maternal cigarette smoking. No correlation between aromatase and aryl hydrocarbon hydroxylase activities in the placentas from both smoking and non smoking mothers was found. These results show that the aromatase activity in human placenta is catalysed by a distinct form of cytochrome P-450 which is different from forms with xenobiotic-metabolising activity, and also show that the aromatase activity is similar in placentas from both smoking and non-smoking mothers. PMID- 4016170 TI - Refractoriness to inhibitory day lengths initiates the breeding season of the Suffolk ewe. AB - Recent evidence indicates that the breeding season of the Suffolk ewe ends because of loss of response to a day length that was previously inductive. This condition of photorefractoriness could potentially also initiate reproduction, as is the case in several long-day breeding rodents. In this study we determined if ewes enter their breeding season because they become refractory to the long ambient photoperiods of late summer. On the summer solstice, 3 groups of ovariectomized ewes (n = 6) bearing s.c. Silastic implants of estradiol (OVX + E) were placed in different day length treatments: 1) natural photoperiod; 2) artificial photoperiod, stimulating natural day lengths; or 3) artificial photoperiod equivalent to that of the summer solstice (16.25L). Entry into the breeding season is associated with a striking (greater than 30-fold) increase in circulating levels of luteinizing hormone (LH). Timing of the onset of the breeding season was not delayed in ewes maintained on the summer solstice photoperiod; LH levels rose simultaneously in all groups. We conclude that ewes normally begin breeding not because they are actively driven to do so by decreasing or short days, but because they become refractory to prevailing long days. Because the pattern of circulating melatonin, which is known to transduce the photoperiodic message, remained entirely appropriate to day length, we believe that the mechanism responsible for photorefractoriness resides in the postpineal processing of the melatonin signal. PMID- 4016171 TI - The effect of exogenous testosterone on homospermic and heterospermic fertility in the cock. AB - Cocks were administered testosterone (T) for 14 days via 0, 1, 2, or 4 Silastic capsules implanted subcutaneously. Each capsule released 1.04 mg of T per day. Concentrations of T in plasma and the proportion of eggs fertilized from homospermic insemination of hens were determined. Concentrations of T in plasma were variable and unaffected by treatment. The proportion of eggs that were fertilized by cocks decreased during treatment with 1 capsule, increased over the experiment in the group with 2 capsules, and increased after treatment ended in the group with 4 capsules. In heterospermic tests, cocks with distinguishable offspring were paired and semen was mixed within pairs. One cock in each pair received either 1 or 4 Silastic capsules containing T for 14 days; the other cock in the pair received none. The proportion of chicks sired by cocks treated with 1 capsule remained unchanged throughout the experiment, whereas the proportion sired by cocks treated with 4 capsules decreased markedly during the recovery period. The response to T was apparently dependent upon dosage and the sensitivity of the cock to T. The concentration of T in the plasma of the cock had little relationship to fertility. These results indicate that heterospermic insemination can be used as a sensitive method to detect the subtle effects of hormonal treatment. PMID- 4016173 TI - Testosterone administration to ovariectomized female rhesus monkeys (Macaca mulatta) reduces the frequency of pulsatile luteinizing hormone secretion. AB - In the male rhesus monkey testosterone (T) retards the frequency of intermittent LH secretion. The purpose of the present study was to determine whether this action of T is demonstrable in the female. Five ovariectomized rhesus monkeys, bearing indwelling cardiac catheters, were implanted s.c. on one or more occasions with T-containing Silastic capsules. Sequential blood samples were collected for 8 h every 10 min before T treatment and usually at 1, 2, 4, and 8 days thereafter. Plasma LH concentrations were measured in duplicate by radioimmunoassay and subsequently analyzed with a computerized algorithm. Sustained increments in circulating T (5-13 ng/ml) in ovariectomized monkeys resulted in a progressive reduction in LH pulse frequencies from approximately 1 pulse every 60 min before initiation of T treatment to 1 pulse every 100-150 min at 48 h thereafter. In most cases the deceleration in pulsatile gonadotropin secretion continued, and by 4-8 days of T treatment LH pulse frequencies as low as 1 pulse every 5 h were observed. The onset of the T-induced deceleration in LH pulse frequency was generally associated with an increase in LH pulse amplitude and with a decline in mean LH levels. This LH response in the female to T treatment was similar to that previously reported for male castrates. PMID- 4016172 TI - Deciduomal response in androgenized rats: effect of age and steroid replacement therapy. AB - Deciduomal response was studied in female rats androgenized with a single injection of 1 mg of testosterone propionate at 5 days of age. Endometrial scratching in immature rats (33 days) elicited a better response in androgenized rats (AF) than in controls (NF) following induction of ovulation or steroid replacement therapy. In adult females receiving cervical stimulation at estrus or induction of ovulation, strong deciduomal response was obtained in NF rats and no response was observed in AF rats. In ovariectomized (OVX) rats receiving 2 mg of progesterone (P), the response in AF was only 50% that of NF rats. Addition of 0.1 mg of estradiol (E2) enhanced the decidualization in NF rats but completely abolished that of AF rats. Following ovariectomy and a period of 12-15 days without any exogenous hormone, an E2 priming treatment (0.2 or 0.5 micrograms) for 3 days followed by a replacement therapy (2.0 mg P + 0.1 or 0.15 micrograms E2) allowed good response in NF rats. The response was reduced by 30-35% in AF rats receiving 0.1 micrograms of E2 during the replacement therapy and by 66% in AF rats receiving 0.15 micrograms of E2. These results indicate that in AF rats the reduction of the response is age dependent, the uterus is more sensitive to E2 than is the uterus of NF rats and the growth response is always submaximal. PMID- 4016174 TI - Increased daily sperm production in the breeding season of stallions is explained by an elevated population of spermatogonia. AB - Seasonal variation in number of spermatogonia and germ cell degeneration was evaluated to determine which mechanism might explain seasonal differences in daily sperm production per testis (DSP/testis) or per g parenchyma (DSP/g) in stallions. Comparing 28 adult stallions (4 to 20 yr old) in each of the nonbreeding (December-January) and breeding (June-July) seasons, the population of type A spermatogonia was more than two times greater (P less than 0.01) in the breeding season. While the number of type B spermatogonia also was elevated (P less than 0.01) in the breeding season, the number of type B spermatogonia/type A spermatogonium was similar (P greater than 0.05) between seasons. Daily sperm production/testis based on each cell type from type B spermatogonia to spermatids with elongated nuclei was lower (P less than 0.01) in the nonbreeding season. Based on DSP/g, there was significant degeneration during the meiotic divisions in the nonbreeding season. However, this reduction in potential spermatozoan production was not significant (P greater than 0.05) when considering DSP/testis. Significant germ cell degeneration also occurred in the breeding season between type B spermatogonia and primary spermatocytes. However, the type A spermatogonial population was sufficiently elevated to override this degeneration and to explain elevated production of sperm in the breeding season of stallions. PMID- 4016175 TI - Bromoergocryptine decreases serum prolactin and delays sexual maturation in male golden hamsters. AB - The role of prolactin during sexual maturation in male golden hamsters was studied. Controls (n = 23) received vehicle and treated animals (n = 23) received 500 micrograms 2-bromo-alpha-ergocryptine (CB154) daily from 10 days of age until 4 or 5 wk of age. Serum prolactin in prepubertal male hamsters was reduced to a nondetectable level by treatment with the dopamine agonist CB154. Flank gland diameter, body weight, testicular and total accessory sex organ weights, and serum testosterone were all significantly lower (P less than 0.05) in the CB154 treated animals. In addition, seminiferous tubule area, seminiferous tubule luminal and cellular areas, and number of late spermatids per tubule cross section were significantly reduced (P less than 0.01) in CB154-treated prepubertal males. Thus, the absence of prolactin retarded sexual maturation in male golden hamsters. These data suggest, that prolactin enhances testosterone production during the process of sexual maturation and supports the development of androgen-dependent tissues. PMID- 4016176 TI - The detection and purification of a cat uterine secretory protein that is estrogen dependent (CUPED). AB - An estrogen-dependent secretory protein (CUPED) was detected and purified from uterine flushings of ovariectomized cats treated with 17 beta-estradiol. The protein was not detected in uterine flushings obtained from untreated ovariectomized animals or estrogen-primed animals treated with progesterone for 4 days. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of uterine flushings showed the presence of 1 or 2 protein bands with relative mobility values less than reduced and denatured thyroglobulin (Mr = 330,000). The protein was purified by differential centrifugation and gel filtration chromatography. Antiserum was raised against this purified protein in rabbits. The specificity of the antiserum to uterine fluid proteins was assessed by immunoblotting of electrophoretically transferred proteins. The antiserum cross-reacted with electrophoretically separated CUPED protein bands in uterine flushings. This protein may represent the content of the estradiol-induced secretory granules present in endometrial epithelial cells. PMID- 4016177 TI - [Safety problems of a microcomputer-equipped infusion apparatus demonstrated with an injection pump]. PMID- 4016178 TI - [Clinical research on the problem of pressure distribution in single- and multichannel infusion apparatus]. PMID- 4016179 TI - [Capillary tube plasma viscometer: methodology, quality control and reference range]. PMID- 4016180 TI - Photon correlation spectroscopy and light scattering of eye lens proteins at high concentrations. AB - The bovine eye lens protein, alpha L crystallin, has been studied with photon correlation spectroscopy and statical light scattering in the concentration range up to 200 g/l in different solvent conditions. At higher concentration (c greater than 70 g/l) the scattering behavior is quite complicated, which results in nonexponential correlation functions. Three methods have been used for the analysis of these correlation functions, namely, cumulant analysis, sum of two exponentials analysis, and exponential sampling method. These methods resulted in very similar results. The highly concentrated solutions contain two scattering entities: the single alpha L crystallin and a rather heterogeneous population of large clusters. The statical light-scattering experiments can be interpreted in the same way and gave consistent results for the dimensions of the large scattering units. The formation of these clusters, which are strong light scatterers, is superimposed on an increasing degree of correlation between the bulk of the alpha L-crystallins, resulting in a net decrease of light scattering as a function of concentration. PMID- 4016181 TI - Double-beam autocompensation for fluorescence polarization measurements in flow cytometry. AB - The degree of depolarization of fluorescent light emitted from an organic dye, which is used as molecular probe, is a powerful tool in probing the microenvironment. By fluorescence depolarization the macromolecular structure can be investigated as well as the the mobility of the marker molecule itself or of the complex formed by the probe. Additional information such as energy transfer rates, donor-acceptor distances, and orientations are also measurable. These data are of particular interest if they can be measured from whole cells. Using flow cytometry, we can analyze a large number of cells with high statistical significance in a short period of time. We describe a newly developed double-beam epi-illumination arrangement for fluorescence polarization measurements that uses an autocompensation technique. This new technique permits the various depolarizing effects within the optical as well as the electronic components of the system to be continually compensated for on a cell by cell basis. Simultaneous measurements of other cell parameters for cell cycle analysis by total fluorescence intensity remains possible. The sensitivity of the system to measure polarization was determined as +/- 0.006 p (0 less than or equal to p less than or equal to 0.5 in isotropic media), which amounts to +/- 1.2% of the maximum p value. Polarization data for latex microspheres plotted in the histogram mode were measured with a standard deviation of 0.006, which proved the high resolution and the high performance of the system. PMID- 4016182 TI - Oxygen quenching of pyrene-lipid fluorescence in phosphatidylcholine vesicles. A probe for membrane organization. AB - Oxygen quenching has been used as an alternative method to study the temperature dependence of the apparent excimer formation constant, kdm, of N-(10-[1-pyrene] decanoyl)-sphingomyelin (Pyr-SPM) in 1-palmitoyl-2-oleoyl-L-alpha phosphatidylcholine (POPC) multilamellar vesicles. In conjunction with the lifetime of Pyr-SPM monomer in the absence of excimer and oxygen, kdm can be determined from the measurements of the monomer intensity as a function of oxygen concentration. The advantage of this method is that kdm can be determined without knowledge of the excimer lifetime and intensity, and without knowledge of the true concentration of oxygen in lipid bilayers. Our results show that kdm increases monotonically with temperature from 16 to 40 degrees C, becomes insensitive to temperature from 40 to 50 degrees C and increases again at 54 degrees C. The temperature-insensitive region corresponds to the temperature range of the phase transition of Pyr-SPM determined by differential scanning calorimetry. This result suggests the existence of Pyr-SPM-enriched domains in POPC vesicles. In contrast, no abrupt change in kdm with temperature occurs in the case of 1-palmitoyl-2-[10-(1-pyrenyl) decanoyl] phosphatidylcholine (Pyr-PC). PMID- 4016183 TI - Dynamic quenchers in fluorescently labeled membranes. Theory for quenching in a three-phase system. AB - The theory for quenching of fluorescently labeled membranes by dynamic quenchers is described for a three-phase system: a fluorescently labeled membrane, a nonlabeled membrane, and an aqueous phase. Two different experimental protocols are possible to determine quenching parameters. Using the first protocol, partition coefficients and bimolecular quenching constants were determined for a hydrophobic quencher in carbazole-labeled membranes in the presence of an unlabeled reference membrane. These parameters determined for 1,1-dichloro-2,2 bis(p-chlorophenyl)ethylene (DDE) using this three-phase analysis were in good agreement with values determined by a two-phase analysis without the reference lipid. Hence, the theory was verified. In the second protocol, the quencher partition coefficient was determined for unlabeled membranes in the presence of a carbazole-labeled reference membrane. Partition coefficients for DDE determined by this method were the same as partition coefficients determined for carbazole labeled membranes using the two-phase analysis. The greater ease in determining partition coefficients and bimolecular quenching constants by the three-phase analysis and, in particular, the ability to determine the partition coefficient in unlabeled membranes make the three-phase analysis especially useful. This method was used to study the effect varying the membrane lipid composition has on the partition coefficient. The data indicate that partition coefficients of DDE in fluid membranes are not dramatically dependent upon polar head group composition, fatty acid composition, or cholesterol content. However, partitioning into gel-phase lipids is at least 100-fold less than fluid-phase lipids. PMID- 4016184 TI - Phase resetting and bifurcation in the ventricular myocardium. AB - With the dynamic differential equations of Beeler, G. W., and H. Reuter (1977, J. Physiol. [Lond.]. 268:177-210), we have studied the oscillatory behavior of the ventricular muscle fiber stimulated by a depolarizing applied current I app. The dynamic solutions of BR equations revealed that as I app increases, a periodic repetitive spiking mode appears above the subthreshold I app, which transforms to a periodic spiking-bursting mode of oscillations, and finally to chaos near the suprathreshold I app (i.e., near the termination of the periodic state). Phase resetting and annihilation of repetitive firing in the ventricular myocardium were demonstrated by a brief current pulse of the proper magnitude applied at the proper phase. These phenomena were further examined by a bifurcation analysis. A bifurcation diagram constructed as a function of I app revealed the existence of a stable periodic solution for a certain range of current values. Two Hopf bifurcation points exist in the solution, one just above the lower periodic limit point and the other substantially below the upper periodic limit point. Between each periodic limit point and the Hopf bifurcation, the cell exhibited the coexistence of two different stable modes of operation; the oscillatory repetitive firing state and the time-independent steady state. As in the Hodgkin Huxley case, there was a low amplitude unstable periodic state, which separates the domain of the stable periodic state from the stable steady state. Thus, in support of the dynamic perturbation methods, the bifurcation diagram of the BR equation predicts the region where instantaneous perturbations, such as brief current pulses, can send the stable repetitive rhythmic state into the stable steady state. PMID- 4016185 TI - Vibrational analysis of the all-trans retinal protonated Schiff base. AB - We have obtained Raman spectra of a series of all-trans retinal protonated Schiff base isotopic derivatives. 13C-substitutions were made at the 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, and 15 positions while deuteration was performed at position 15. Based on the isotopic shifts, the observed C--C stretching vibrations in the 1,100-1,400 cm-1 fingerprint region are assigned. Normal mode calculations using a modified Urey-Bradley force field have been refined to reproduce the observed frequencies and isotopic shifts. Comparison with fingerprint assignments of all trans retinal and its unprotonated Schiff base shows that the major effect of Schiff-base formation is a shift of the C14--C15 stretch from 1,111 cm-1 in the aldehyde to approximately 1,163 cm-1 in the Shiff base. This shift is attributed to the increased C14--C15 bond order that results from the reduced electronegativity of the Schiff-base nitrogen compared with the aldehyde oxygen. Protonation of the Schiff base increases pi-electron delocalization, causing a 6 to 16 cm-1 frequency increase of the normal modes involving the C8--C9, C10--C11, C12--C13, and C14--C15 stretches. Comparison of the protonated Schiff base Raman spectrum with that of light-adapted bacteriorhodopsin (BR568) shows that incorporation of the all-trans protonated Schiff base into bacterio-opsin produces an additional approximately 10 cm-1 increase of each C--C stretching frequency as a result of protein-induced pi-electron delocalization. Importantly, the frequency ordering and spacing of the C--C stretches in BR568 is the same as that found in the protonated Schiff base. PMID- 4016186 TI - On the mechanism of muscular contraction. AB - A thermodynamic analysis is presented for the energy conversion by muscle contraction. During the cyclic processes the major change in energy of the myosin actin system is due to bond formation between myosin heads and actin. To account for the high efficiency of a working muscle the work done is connected directly to the formation of myosin-actin bond. It is suggested that successively stronger bonds are formed by a stepwise movement of myosin heads over an interval between two troponin molecules on the actin filament. At the end of the interval, where the bond has maximum strength, energy is supplied to break the bond. Here the work is not primarily connected to the 45 degrees rotation of myosin heads as is commonly done. A way of separating the different kinds of energy losses is presented. PMID- 4016187 TI - Donnan potential and surface potential of a charged membrane. AB - A model is presented for the electrical potential distribution across a charged biological membrane that is in equilibrium with an electrolyte solution. We assume that a membrane has charged surface layers of thickness d on both surfaces of the membrane, where the fixed charges are distributed at a uniform density N within the layers, and that these charged layers are permeable to electrolyte ions. This model unites two different concepts, that is, the Donnan potential and the surface potential (or the Gouy-Chapman double-layer potential). Namely, the present model leads to the Donnan potential when d much greater than 1/k' (k' is the Debye-Huckel parameter of the surface charge layer) and to the surface potential as d----0, keeping the product Nd constant. The potential distribution depends significantly on the thickness d of the surface charge layer when d less than or approximately equal to 1/k'. PMID- 4016188 TI - The effect of oxygen on the amplitude of photodriven electron transfer across the lipid bilayer-water interface. AB - The surprisingly small effect of oxygen on photoelectron transfer in pigmented lipid bilayers is traced to a short lifetime of the excited states. Decreasing the oxygen concentration by greater than 100-fold decreases the half saturating concentration of acceptor by only threefold and has no effect on the maximum photovoltage observed at acceptor saturation. This holds true for both magnesium octaethylporphyrin and chlorophyll with both ferricyanide and methyl viologen as acceptors. Since oxygen quenches excited states at near the encounter limit, the lifetime of reactive state must be short, less than 100 ns. About 100-fold higher concentrations of acceptor are required to quench the fluorescence (in liposomes) than to saturate the photoeffect. Thus the reactive state is most likely the triplet. The short life of the excited state is caused by concentration quenching, i.e., their reaction with ground state molecules. The increase of photovoltage with increasing pigment concentration shows that this quenching in a condensed form of the pigment produces ions that lead to the observed photovoltage by interfacial reaction of the anion with acceptor. PMID- 4016189 TI - Red blood cell deformation in shear flow. Effects of internal and external phase viscosity and of in vivo aging. AB - Shear deformation of young and old human red blood cells was examined over a range of shear stresses and suspending phase viscosities (eta o) using a cone plate Rheoscope. The internal viscosities (eta i) of these cell types differ, and further changes in internal viscosity were induced by alteration of suspension osmolality and hence cell volume. For low suspending viscosities (0.0555 or 0.111 P) old cells tended to tumble in shear flow, whereas young cells achieved stable orientation and deformed. Changes in osmolality, at these external viscosities, altered the percentage of cells deforming, and for each cell type threshold osmolalities (Osm-50) were determined where 50% of cells deformed. The threshold osmolalities were higher for younger cells than for older cells, but the internal viscosities of the two cell types were similar at their respective Osm-50. Threshold osmolalities were also higher for the higher external viscosity, but the ratio of internal to external viscosities (i.e., eta i/eta o) was nearly constant for both external viscosities. Deformation of stably oriented cells increased with increasing shear stress and approached a value limited by cell surface area and volume. For isotonic media, over a wide range of external viscosities and shear stresses, deformation was greater for younger cells than for older cells. However, deformation vs. shear stress data for the two cell types became nearly coincident if young cells were osmotically shrunk to have their internal viscosity close to that for old cells. Increases in external viscosity, at constant shear stress, caused greater deformation for all cells. This effect of external viscosity was not equal for young and old cells; the ratio of old/young cell deformation increased with increasing eta o. However, if deformation was plotted as a function of the ratio lambda = eta i/eta o, at constant shear stress, young and old cell data followed similar paths. Thus the ratio lambda is a major determinant of cell deformation as well as a critical factor affecting stable orientation in shear flow. PMID- 4016190 TI - Characterization of the chromophore of the third rhodopsin-like pigment of Halobacterium halobium and its photoproduct. AB - Halobacterium halobium contains at least three retinal-containing pigments: bacteriorhodopsin, halorhodopsin, and a third rhodopsin-like pigment (tR) absorbing at approximately 590 nm, tR590. Illumination of tR590 gives rise to a very long-lived blue absorbing photoproduct, tR370. Using high-performance liquid chromatography we show that the chromophore of tR590 is primarily all-trans retinal and its conversion by light to tR370 causes the chromophore to isomerize primarily to the 13-cis conformation. Irradiation of the tR370 gives rise to a transient photoproduct absorbing at approximately 520 nm that decays back to the initial pigment tR590. In addition to all-trans retinal, the apomembrane of tR can also combine with 13-cis retinal but not with the 9- or 11-cis isomers. PMID- 4016191 TI - Fixed charges of the heart muscle interstitium. AB - The interstitium of the heart muscle is primarily composed of ground substance. The glycoproteins and proteoglycans that formed the ground substance bore negative charges at neutral pH like the glycosaminoglycans and proteoglycans of the water-rich phase of the interstitium. Microelectrodes were used to look for the existence of an electrical potential between the interstitium of the rabbit papillary muscle and an ambient medium. Evidence is presented for the existence of such an electrical potential. When the ambient solution was a Krebs solution, this potential was evaluated at -5.7 mV. This electrical potential is dependent on the filling solution of the microelectrodes and on the ambient medium; in rabbit serum, the electrical potential diminished to -0.6 mV. Assuming that this potential is a measure of the Donnan potential, the Cl and Na activities in the interstitium were evaluated to 76 and 135 mM when the rabbit papillary muscle was superfused with a Kreb's solution. PMID- 4016193 TI - The rate of diffusion of Ca2+ and Ba2+ in a nerve cell body. AB - A spectrophotometric method was developed to directly measure the diffusion rate of Ca2+ and some other ions in nerve cell bodies, using pulsed ionophoretic injections and an optical microprobe to record locally absorbance changes of the dye arsenazo III. We report here that Ca2+ and Ba2+ diffuse at approximately the same rate in nerve soma cytoplasm, having effective diffusion coefficients in the range of 7-12 X 10(-7) cm2/s, while identical measurements conducted in an electrolytic solution yielded values of 5.2 X 10(-6) cm2/s for Ca and 5.4 X 10( 6) cm2/s for Ba. The results are discussed in relation to the mechanisms that regulate the intracellular concentration of free Ca. PMID- 4016192 TI - Novel fluorescence method to visualize antibody-dependent hydrogen peroxide associated "killing" of liposomes by phagocytes. AB - We have developed a new methodology to examine effector-cell-mediated immune attack using liposomes as targets. Hydrogen-peroxide-associated killing of liposomes was observed with fluorescence intensification microscopy. Liposomes were composed of 98-99 mol % egg phosphatidylcholine and 1-2 mol % dinitrophenyl lipid hapten. Anti-dinitrophenyl IgG antibody was used to opsonize liposomes. Liposomes were loaded with dihydroxymandelic acid (DHMA) and peroxidase. Macrophage- or neutrophil-mediated recognition of liposomes triggers the release of H2O2 and other oxidative products. Upon interaction of H2O2 or OH radical with liposome contents, DHMA dimerizes forming a fluorescent derivative. Our studies indicate that individual living neutrophils and macrophages deposit oxidative products in a heterogeneous fashion among bound targets. PMID- 4016194 TI - Depolarization spectrum of diffracted light from muscle fiber. The intrinsic anisotropy component. AB - The depolarization signal of the diffraction patterns from muscle fibers includes information that differs from that of transmission birefringence experiments. Although both the birefringence studies and the phase shift studies of Yeh et al. (Yeh, Y, and G. Pinsky, 1983, Biophys. J., 42:83-90; Yeh, Y., M. E. Corcoran, R. J. Baskin, and R. L. Lieber, 1983, Biophys. J., 44:343-351) include inseparable intrinsic and form contributions, the present analysis shows that the magnitude of the E-field components of diffracted light is affected only by the intrinsic contribution. We have analyzed the amplitude portion of the data of which the phase shift portion had previously been reported (Yeh, Y., M. E. Corcoran, R. J. Baskin, and R. L. Lieber, 1983, Biophys. J., 44:343-351). For the relaxed-to rigor transition, these field amplitudes also exhibit changes when ATP concentration is decreased. The observed decrease in optical depolarization upon rigor is consistent with the idea that optically anisotropic elements move away from the myosin thick filament under such conditions. PMID- 4016195 TI - Repulsive forces in lecithin glycol lamellar phases. AB - The repulsive pressure vs. distance for phospholipid bilayers in glycol has been determined from vapor pressure measurements. The magnitude of this pressure is similar to the case when water is present between the lipid bilayers. Hence, an interaction directly corresponding to the previously reported hydration force is shown also for nonaqueous lecithin/solvent systems. PMID- 4016196 TI - Absolute measurement of enhanced fluctuations in assemblies of biomolecules by ultrasonic techniques. AB - By expressing the fluctuation-dissipation theorem explicitly, equations are obtained for the ultrasonic relaxation amplitudes that contain one single molecular parameter, i.e., the fluctuation, or the sum of fluctuations. The absolute measurement of this parameter is therefore possible. The equations apply to a two-state system, to a multistate system and to a linear Ising chain as well. In an aqueous medium, where molar volume changes are important, the ultrasonic relaxation amplitudes are proportional to the volume fluctuations. For assemblies of biomolecules that exhibit enhanced ultrasonic absorption on assembly it is possible to measure the increase on assembly of the sum of fluctuations. In view of application to tobacco mosaic virus protein aggregates, examples are given in which the fluctuations associated with two normal modes of relaxation are equally enhanced when the difference of conformational stability of the states is reduced. The corresponding observable changes of the ultrasonic spectra are described. PMID- 4016197 TI - The intrinsic tyrosine fluorescence of histone H1. Steady state and fluorescence decay studies reveal heterogeneous emission. AB - In wavelength-resolved steady state spectra we observe three different kinds of emission from histone H1, a class A protein with only a single tyrosine residue. Unfolded H1 emissions that peak at approximately 300 and 340 nm can both be excited maximally at approximately 280 nm. Another, peaking much further to the red at approximately 400 nm, can be excited maximally at approximately 320 nm. The 300-nm fluorescence can be resolved by lifetime measurements into three components with decay times of approximately 1, 2, and 4 ns. On sodium-chloride induced refolding of H1, simplification of the emission properties occurs. The 340 and 400-nm components disappear while the two shorter lifetime components of the 300-nm band diminish in amplitude and are replaced by the 4-ns decay. We believe that the 340-nm emission is tyrosinate fluorescence resulting from excited-state proton transfer. The origin of the 400-nm emission remains uncertain. We assign the 1 and 2-ns components of the 300-nm emission to two states of tyrosine in denatured H1 and the 4-ns decay to fluorescence of the single tyrosine residue in the globular region of refolded H1. Our results support the contention that salt induced folding of H1 is a cooperative two state process, and permit us to better understand the previously reported increases in fluorescence intensity and anisotropy on salt-induced folding. PMID- 4016198 TI - Kinetic differences at low temperatures between R and T state carbon monoxide carp hemoglobin. AB - We use the low-temperature recombination kinetics of carbon monoxide with carp hemoglobin to determine that the R and T states of hemoglobin exhibit different low-temperature geminate recombination kinetics. The peak of the fitted Gaussian activation energy spectrum is at 1.5 kcal/mol for R state and 1.8 kcal/mol for T state. The distribution in activation energies is fit well by the Agmon-Hopfield linear strain model. The T state is fit with a stronger elastic constant than R, and has a larger displacement of the protein conformation coordinate than does the R state, indicating that the T state does have a significantly greater rigidity and also stores more strain energy in its conformational states than does R hemoglobin. The pre-exponential in the activation energy spectrum is only a factor of two greater in the R than the T state and the low-temperature activation energy spectrum does not correctly predict the difference in the on rates for R and T states at 300 degrees K, indicating that processes removed from the binding site are important in cooperativity. PMID- 4016199 TI - The primary event in vision investigated by time-resolved fluorescence spectroscopy. AB - The picosecond fluorescence kinetics and quantum yield from bovine rhodopsin were measured in the 5-40 degrees K range. The fluorescence rise and decay times are faster than our resolution of 15 ps (full width at half maximum) over this entire temperature range. The size of the observed emission was also temperature independent, and we find that the upper limit of rhodopsin's fluorescence quantum yield to be phi f approximately equal to 10(-5). Replacing all of rhodopsin's exchangeable protons with deuterons by suspending rhodopsin in D2O had no effect on either the kinetics of the emission or the value of the quantum yield. Our data provide strong confirmation of the idea that the first step in the visual process is an excited-state cis-to-trans isomerization about the C11-C12 double bond of retinal. PMID- 4016200 TI - Epithelial water transport in a balanced gradient system. AB - The relationship between epithelial fluid transport, standing osmotic gradients, and standing hydrostatic pressure gradients has been investigated using a perturbation expansion of the governing equations. The assumptions used in the expansion are: (a) the volume of lateral intercellular space per unit volume of epithelium is small; (b) the membrane osmotic permeability is much larger than the solute permeability. We find that the rate of fluid reabsorption is set by the rate of active solute transport across lateral membranes. The fluid that crosses the lateral membranes and enters the intercellular cleft is driven longitudinally by small gradients in hydrostatic pressure. The small hydrostatic pressure in the intercellular space is capable of causing significant transmembrane fluid movement, however, the transmembrane effect is countered by the presence of a small standing osmotic gradient. Longitudinal hydrostatic and osmotic gradients balance such that their combined effect on transmembrane fluid flow is zero, whereas longitudinal flow is driven by the hydrostatic gradient. Because of this balance, standing gradients within intercellular clefts are effectively uncoupled from the rate of fluid reabsorption, which is driven by small, localized osmotic gradients within the cells. Water enters the cells across apical membranes and leaves across the lateral intercellular membranes. Fluid that enters the intercellular clefts can, in principle, exit either the basal end or be secreted from the apical end through tight junctions. Fluid flow through tight junctions is shown to depend on a dimensionless parameter, which scales the resistance to solute flow of the entire cleft relative to that of the junction. Estimates of the value of this parameter suggest that an electrically leaky epithelium may be effectively a tight epithelium in regard to fluid flow. PMID- 4016201 TI - Novel fluorescence method to visualize antibody-dependent hydrogen peroxide associated "killing" of liposomes by phagocytes. AB - We have developed a new methodology to examine effector-cell-mediated immune attack using liposomes as targets. Hydrogen peroxide-associated killing of liposomes was observed with fluorescence intensification microscopy. Liposomes were composed of 98-99 mol % egg phosphatidylcholine and 1-2 mol % dinitrophenyl lipid hapten. Anti-dinitrophenyl IgG antibody was used to opsonize liposomes. Liposomes were loaded with dihydroxymandelic acid (DHMA) and peroxidase. Macrophage- or neutrophil-mediated recognition of liposomes triggers the release of H2O2 and other oxidative products. Upon interaction of H2O2 or OH radical with liposome contents, DHMA dimerizes forming a fluorescent derivative. Our studies indicate that individual living neutrophils and macrophages deposit oxidative products in a heterogenous fashion among bound targets. PMID- 4016202 TI - Effect of divalent cations on the assembly of neutral and charged phospholipid bilayers in patch-recording pipettes. AB - Monolayers of the negatively charged phospholipid phosphatidylserine (PS) and of the amphoteric phospholipid dioleoylphosphatidylethanolamine (DOPE) were used to assemble bilayers at the tip of patch-recording pipettes. PS bilayers, with seal resistances in the range of gigaohmns (gigaseals), could only be generated when millimolar concentration of divalent cations, Ca++, Mg++, or Ba++ were present in the pipette and bath solutions. In contrast, gigaseals of DOPE were independent of divalent ion concentration in the pH range where DOPE is predominantly neutral (pH 6.5) or positively charged (pH 1.5). At pH 10.0, when most DOPE molecules bear a net negative charge, gigaseals became divalent cation dependent, in a manner quantitatively similar to that of PS at neutral pH. The results indicate that divalent cations play an important role in stabilizing gigaseals of negatively charged lipid but are of no consequence in neutral or positively charged seals. PMID- 4016203 TI - Distributed kinetics of decay of the photovoltage at the lipid bilayer-water interface. AB - The decay kinetics of the photovoltage formed on pulsed illumination of a chlorophyll a- (chl a-) containing lecithin-bilayer adjacent to a ferricyanide solution on one side show characteristics of a system with distributed rate constants, i.e., the decay approaches linearity in log of time. The kinetics can be explained by a distribution of the chl cation over a few angstroms depth in the interfacial region of the bilayer and a rate constant exponentially dependent on distance as expected from tunneling theory. Addition of the donor ferrocyanide both increases the average rate and sharpens the distribution. There is a competitive inhibition by ferricyanide of the reaction of pigment cation with ferrocyanide. Removal of oxygen increases the rate of decay when an acceptor, methyl viologen or anthraquinone-2-sulfonate, forms oxygen-sensitive radicals. The cation charge does not cross the bilayer on a time scale of less than 0.01 s. These data define a reaction localized precisely in the finite interfacial region of the lipid bilayer-water interface. PMID- 4016204 TI - Temperature dependence of photovoltages generated by bacteriorhodopsin. AB - The temperature dependence of the photovoltage developed by a model membrane containing bacteriorhodopsin (BR) is studied. The model membrane is formed by first coating a thin Teflon sheet with lipid and then fusing BR vesicles to it. The time course of the photoresponse is resolved down to 1 microsecond. The photoresponse is taken to be a sum of exponentials. Exponential time constants and amplitudes are determined by an analysis of the photoresponse with a photovoltage vs. log time plot, correlation filter, and nonlinear least-squares routine. The photovoltage is taken to be the sum of three exponentials but only two of the three time constants are resolved. Both are temperature dependent and indicate a thermally activated transport process. The corresponding activation energies are 55 kJ/mol and 62 kJ/mol. Since the photovoltage is proportional to charge times displacement the corresponding charge displacements are 11 and 34 A assuming a total displacement of 45 A. The remaining exponential term corresponds to a small negative transient in the photovoltage that has a rise time less than 1 microsecond even at -20 degrees C. The calculated charge displacement is estimated to be less than 2 A. PMID- 4016205 TI - The vibrational spectrum of water in liquid alkanes. AB - The water wire hypothesis of hydrogen-ion transport in lipid bilayers has prompted a search for water aggregates in bulk hydrocarbons. The asymmetric stretching vibration of the water dissolved in n-decane and in a number of other alkanes and alkenes has been observed. The water band in the alkanes is very wide and fits to the results of a J-diffusion calculation for the water rotation. This implies that the water is freely rotating between collisions with the solvent and certainly not hydrogen bonded to anything. The existence of water aggregates is thus most unlikely. In contrast, water in an alkene is hydrogen bonded to the solvent molecules (although not to other water molecules) and shows an entirely different spectrum. PMID- 4016207 TI - Detailed mechanics of membrane-membrane adhesion and separation. I. Continuum of molecular cross-bridges. AB - The mechanics of membrane-membrane adhesion are developed for the approximation that the molecular cross-bridging forces are continuously distributed as a normal stress (force per unit area). The significance of the analysis is that the finite range of the cross-bridging forces and the microscopic contact angle are not assumed negligible. Since the cross-bridging and adhesion forces are finite range interactions, there are two membrane regions: a free zone where the membranes are not subject to attractive forces; and an adherent zone where the membranes are held together by attractive stresses. The membrane is treated as an elastic continuum. The approach is to analyze the mechanics for each zone separately and then to require continuity of the solutions at the interface between the zones. Final solution yields the membrane contour and stresses proximal to and within the contact zone as well as the microscopic contact angle at the edge of the contact zone. It is demonstrated that the classical Young equation is consistent with this model. The results show that the microscopic contact angle becomes appreciable when the strength of adhesion is large or the length of the cross bridge is large; however, the microscopic contact angle approaches zero as the membrane elastic stiffness increases. The solution predicts the width of the contact zone over which molecular bonds are stretched. It is this boundary region where increased biochemical activity is expected. In the classical model presented here, the level of tension necessary to oppose spreading of the contact is equal to the minimal level of tension required to separate the adherent membranes. This behavior is in contrast with that derived for the case of discrete molecular cross-bridges where the possibility of different levels of tension associated with adhesion and separation is introduced. The discrete cross bridge case is the subject of a companion paper. PMID- 4016206 TI - 23Na and 39K nuclear magnetic resonance studies of perfused rat hearts. Discrimination of intra- and extracellular ions using a shift reagent. AB - High-resolution 23Na and 39K nuclear magnetic resonance (NMR) spectra of perfused, beating rat hearts have been obtained in the absence and presence of the downfield shift reagent Dy(TTHA)3- in the perfusing medium. Evidence indicates that Dy(TTHA)3- enters essentially all extracellular spaces but does not enter intracellular spaces. It can thus be used to discriminate the resonances of the ions in these spaces. Experiments supporting this conclusion include interventions that inhibit the Na+/K+ pump such as the inclusion of ouabain in and the exclusion of K+ from the perfusing medium. In each of these experiments, a peak corresponding to intracellular sodium increased in intensity. In the latter experiment, the increase was reversed when the concentration of K+ in the perfusing medium was returned to normal. When the concentration of Ca2+ in the perfusing medium was also returned to normal, the previously quiescent heart resumed beating. In the beating heart where the Na+/K+ pump was not inhibited, the intensity of the intracellular Na+ resonance was less than 20% of that expected. Although the data are more sparse, the NMR visibility of the intracellular K+ signal appears to be no more than 20%. PMID- 4016208 TI - Detailed mechanics of membrane-membrane adhesion and separation. II. Discrete kinetically trapped molecular cross-bridges. AB - In general, membrane-membrane adhesion involves specific molecular binding and cross-bridging reactions. The ideal, classical view is that near equilibrium the forces required to separate adhesive contacts are essentially equal to those induced in the membrane when the contact is formed. In contrast to the classical view, experimental observations often show that negligible levels of tension are induced by the adhesive contact even though the tension required to separate the contact is large enough to rupture the membrane. The deviation in tension levels associated with contact formation and separation appears to be due to the sparse distribution of strong molecular cross-bridges. Here, the mechanics of membrane membrane adhesion and separation is developed for the case of discrete, kinetically trapped cross-bridges. The solution is obtained by numerical computation of the membrane contour that minimizes the total free energy (membrane elastic energy of deformation plus cross-bridge energies) in the contact zone. This solution is matched with the analytical solution for membrane stresses and geometry derived for the adjacent, unbridged zone. The results yield specific values of the macroscopic tension applied to the membrane in the plane region away from the contact zone and the microscopic angle at the edge of the contact zone. Two disparate values of the macroscopic tension are found: (a) the minimum tension required to separate the adherent membranes; and (b) the maximum tension induced in the membranes when the contact is formed (i.e., the level of tension at which the contact will just begin to spread). The results show that the deviation between these two tensions can be very large and depends strongly on the surface density of cross-bridges. In addition, the results provide an estimate of the restraining forces that anchor receptors within the plane of the membrane. PMID- 4016209 TI - Donnan potentials in rabbit psoas muscle in rigor. AB - Collins and Edwards (1971, Am. J. Physiol., 221:1130-1133) have shown that a tissue potential can be measured with microelectrodes in glycerinated muscle and that this potential is consistent with a Donnan equilibrium of small ions due to the concentration of net fixed electric charge on the contractile proteins. This approach has been combined with x-ray and light diffraction measurements of the muscle lattice dimensions, and the data are used to determine the thick filament charge and thin filament charge under a variety of different conditions. The thick filament charge is a function of the bathing solution, in particular its pH and ionic composition. These parameters are important in determining the volume of the equilibrium lattice and possibly are involved in the contraction mechanism itself. PMID- 4016210 TI - Donnan potentials from the A- and I-bands of glycerinated and chemically skinned muscles, relaxed and in rigor. AB - Using a combination of microelectrode measurements and high-power microscopy we have demonstrated that different Donnan potentials can be recorded from the A- and I-bands of glycerinated and chemically skinned muscles in rigor, so that the A-band fixed charge concentration exceeds the I-band fixed charge concentration in the rigor condition. In relaxation the two potentials, and therefore the two charge concentrations, are equal in the two bands. X-ray data are presented for relaxed and rigor rat semitendinosus muscle, chemically skinned, and actin and myosin filament charges are calculated under a variety of conditions. Our conclusions are that (a) the fixed (protein) charge is different in the A- and I bands of striated muscle in the rigor state; (b) the fixed charges are equal in the A- and I-bands of relaxed muscle; (c) the largest charge change between relaxation and rigor is on the thick filament. This occurs whether or not the myosin heads are cross-linked to the thin filaments. (d) Possibly an event on the myosin molecule, the binding of ATP (or certain other ligands) causes a disseminated change that modifies the ion-binding capacity of the myosin rods, or part of them. PMID- 4016211 TI - Fluorometry of turbid and absorbant samples and the membrane fluidity of intact erythrocytes. AB - In employing intrinsic or extrinsic fluorophores in the study of whole cells, or other strongly absorbant and/or scattering samples, the measured fluorescence intensity and polarization is seriously affected by absorption and scattering within the sample cuvet. These artifacts are analyzed and simple protocols are provided for overcoming them. An expression relating attenuation of the observed emission anisotropy to sample turbidity is derived. The validity of the method is confirmed by experiments in which the emission anisotropies and fluorescence yields of membrane probes in intact erythrocytes was measured with precision. It is also shown that the rotational mobility of the membrane probe 1-phenyl-3-(2 naphthyl)-2-pyrazoline is the same for intact erythrocytes and ghosts. These protocols are particularly useful in measuring the intrinsic fluorescence yield ratio for excimeric and monomeric emission of pyrene-containing membrane probes. This provides a method for determining the local lateral mobility of excimeric probes in intact erythrocytes. PMID- 4016212 TI - Assessment of the symmetry of stem-cell mitoses. AB - A model of Paneth-cell renewal in the small intestinal epithelium is used to estimate the probability that epithelial stem-cell mitoses are symmetric in the sense that they produce two cells of the same type. I found that counts of the number of Paneth cells per crypt (Paneth cells are terminally differentiated cells derived from small intestinal epithelial stem cells) support a model in which most, if not all, stem-cell mitoses are symmetric. PMID- 4016213 TI - The magnetic field of a single axon. A comparison of theory and experiment. AB - The magnetic field and the transmembrane action potential of a single nerve axon were measured simultaneously. The volume conductor model was used to calculate the magnetic field from the measured action potential, allowing comparison of the model predictions with the experimental data. After analyzing the experiment for all systematic errors, we conclude that the shape of the magnetic field can be accurately predicted from the transmembrane potential and, more importantly, the shape of the transmembrane potential can be calculated from the magnetic field. The data are used to determine ri, the internal resistance per unit length of the axon, to be 19.3 +/- 1.9 k omega mm-1, implying a value for the internal conductivity of 1.44 +/- 0.33 omega -1 m-1. Magnetic measurements are compared with standard bioelectric techniques for studying nerve axons. PMID- 4016214 TI - Conformation of double-stranded polydeoxynucleotides in solution by proton two dimensional nuclear Overhauser enhancement spectroscopy. PMID- 4016215 TI - Model computations on the differential scattering of circularly polarized light (CIDS) by dense macromolecular particles. PMID- 4016216 TI - The physical origin of the low solubility of nonpolar solutes in water. PMID- 4016217 TI - Base tilt of poly[d(A)]-poly[d(T)] and poly[d(AT)]-poly[d(AT)] in solution determined by linear dichroism. PMID- 4016218 TI - Crystal structure of the cis-syn photodimer of thymidylyl (3'-5') thymidine cyanoethyl ester. PMID- 4016219 TI - A low-salt form of poly(dG-5M-dC).poly(dG-5M-dC). PMID- 4016220 TI - [Changes in water metabolism in rats under the influence of naloxone: role of vasopressin]. AB - The effect of naloxone (0.6 mg; 1.2 mg; 2.4 mg X kg-1) were compared in normal Long Evans (N) and Brattleboro (D.I.) conscious rats. Naloxone did not change the values of drinking, diuresis, food intake, blood pressure, Na+ and K+ urinary excretion measured during 24 hours. During the two hours following drug injection, naloxone (1.2 and 2.4 mg X kg-1) reduced diuresis in normal as well as in D.I. rats. Water drinking was only modified in D.I. rats: this effect was shown to be a consequence of antidiuresis. These results suggest that the antidiuretic properties of naloxone are independent of vasopressin secretion. They do not support in a role of opiate receptors on vasopressin secretion in normal hydrated animals. PMID- 4016221 TI - Relationship between the age of platelets and their megakaryocytopoiesis inhibiting effect. AB - Homogenate made from young platelets suppressed thrombocytopoiesis in mice more effectively than homogenate made from old platelets. To achieve the same suppressive effect as that of young platelets, homogenate made from twice as many old platelets were needed. PMID- 4016222 TI - Initiation of DNA synthesis in the liver and other tissues of adult mice by a growth factor (EACF) isolated from acellular fluid of the Ehrlich ascites carcinoma. AB - The mitogenic effect of a new growth factor that we recently isolated from the acellular ascitic fluid of the Ehrlich ascites carcinoma grown in vivo was examined. We have called this factor EACF (Ehrlich ascites carcinoma factor). EACF caused initiation of DNA synthesis in the liver, submandibular gland, exorbital lacrimal gland and epithelium of the tongue of adult mice after i.p. injection at a protein concentration of 3 micrograms per 25 g of body weight. For all tissues examined, except the tongue, EACF initiated DNA synthesis at about 48 to 60 h after injection, with the maximum effect at approx. 85 h, and the stimulatory effect lasting approx. 60 h. The initiation of DNA synthesis in liver, which is normally characterized by only an occasional cell passing through the S phase, by EACF is of particular interest. The initiation of DNA synthesis in the liver was not prevented by hypophysectomy. Evidence also indicates that a similar heat-labile growth promoting factor(s) is present in calf serum. PMID- 4016223 TI - Assessment of the antidiabetic activity of epicatechin in streptozotocin-diabetic and spontaneously diabetic BB/E rats. AB - (-)-Epicatechin has previously been suggested to rapidly reverse alloxan diabetes in rats. We have assessed the therapeutic value of the compound in two further animal models of insulin-dependent diabetes mellitus, namely streptozotocin diabetic rats and the spontaneously diabetic BB/E rat. There was no indication of a reversal of established diabetes in either the streptozotocin-diabetic or the spontaneously diabetic BB/E rats. Moreover, epicatechin also failed to halt the progression of the disease in prediabetic BB/E rats. Earlier claims of the potential use of epicatechin as an antidiabetic agent must therefore be treated with some caution. PMID- 4016224 TI - Aggregation and fusion of lipid vesicles induced by diphtheria toxin at low pH: possible involvement of the P site and the NAD+ binding site. AB - Model membranes have been used to study the interaction between diphtheria toxin and lipids. We report here on the ability of this toxin to induce, at low pH, fusion and aggregation of asolectin lipid vesicles. Resonance energy transfer experiments using lipid fluorescent probes make it possible to discriminate between these two processes. PMID- 4016225 TI - Synthesis of (+) and (-) RNA molecules of potato spindle tuber viroid (PSTV) in isolated nuclei and its impairment by transcription inhibitors. AB - Transcription studies with highly purified potato cell nuclei in combination with a 'transcription-hybridization analysis' unequivocally demonstrate that the nucleus is the subcellular site where the entire process of PSTV replication takes place. Inhibition experiments with actinomycin D and alpha-amanitin furthermore suggest that the nuclear DNA-dependent RNA polymerases I and II are involved in the synthesis of PSTV (+) and (-) RNA, respectively. PMID- 4016226 TI - [Structural changes in the pulmonary vessels and parenchyma in experimental hypercholesterolemia and atherosclerosis]. AB - Light and electron microscopy were employed to study the microcirculatory bed (MCB), intraorganic vessels and lung tissue in rabbits in the first hours (1, 3, 6, 15, 24 and 48 h) after a single administration of cholesterol (ChS) and in the course of the development of experimental atherosclerosis. The MCB demonstrated changes such as dilatation of the venular part, arteriolar constriction, red cell aggregation in capillaries and venules, and stases. At the early stages of experimental atherosclerosis induced by the diet the permeability of the air blood barrier and the synthesis of lung surfactant were found to be deranged. Vessel-tissue changes in the lungs progressed with an increase in the length of the diet (1-8 months) and were alike the picture seen in chronic nonspecific lung diseases, particularly in what is called senile emphysema. A relationship was established between the degree of changes in the MCB and HCh gravity. Atherosclerotic lesions in the intraorganic arteries occur and progress parallel with the development of this process in the intramural arteries of the myocardium. The data obtained attest to an important role of lipid metabolism disorders in the development of lung pathology and may have a certain significance in specifying the pathogenesis of chronic nonspecific lung diseases, especially. PMID- 4016227 TI - [Collagen resorption by macrophages and fibroblasts in liver cirrhosis]. AB - Intracellular lysis of collagen by macrophages and fibroblasts in liver cirrhosis and during its reverse development has been shown in experiments on mice by electron microscopy and electron histochemistry. Based on the data obtained it is concluded that in the process under consideration, there occur phagocytosis and intracellular resorption of collagen by macrophages and fibroblasts and that intracellular collagen lysis in the cells in question occurs in the presence of active involvement in the process of lysosomal enzymes. PMID- 4016228 TI - [Functional activity of the structures of the medulla oblongata in rats with arterial hypertension of renal origin (histoenzymological research)]. AB - A quantitative histochemical study of succinate dehydrogenase (SDH) and NADH dehydrogenase (NADH-D) activity in medulla oblongata structures was accomplished in rats with arterial renovascular hypertension of the "2 kidneys-2 clips" type lasting 5 months. The systolic arterial blood pressure measured by the tail-cuff method was 179 +/- 4 mm Hg in hypertensive rats versus 108 +/- 3 mm Hg in control. There was a significant elevation of SDH activity in the ventral reticular and commissural nuclei, while in the neurons of the vagus dorsal and ambiguous nuclei it was lowered. NADH-D activity was significantly increased in the neuropil of the hypoglossal nerve nucleus and reduced in its neurons. The general trend was also revealed toward reduction of the maximal and elevation of the minimal activities in other nuclei. These metabolic alterations reflect changes in the functional activity of vasomotor and other structures of the medulla oblongata in renovascular hypertension. PMID- 4016229 TI - [Biopotential amplifier with nonlinear volt-ampere characteristics for recording low-amplitude pulses]. AB - An amplifier with non-linear volt-ampere characteristics for recording low amplitude nerve pulse activity is offered. It permits recording impulses with an amplitude exceeding the noise by 3-5 microV and afferent impulse activity of rat taste nerves. PMID- 4016230 TI - [Electron microscopic research on capillary regeneration in skeletal muscle after mechanical damage]. AB - At early stages the regeneration of the capillaries in adult rats in the focus of the skeletal muscle traumatic injury proceeds together with regeneration of muscle elements. However, it is retarded to some extent. The capillaries are formed within the borders of the basal membranes of the destroyed vessels or grow de novo from poorly differentiated interstitial cells. PMID- 4016231 TI - [Fluorescence spectra of the SIF cells in rat neuroganglia]. AB - The spectral curves of emission of paraform-induced fluorophores in small, intensely fluorescent (SIF) cells in lumbar ganglia of the sympathetic trunk and in the major pelvic ganglion were compared with the fluorescence spectra of lipofuscin granules in the perikaryons of the neurons of the vagus inferior ganglion. As a rule, the fluorescence spectra of SIF cells correlate with the content in them of catecholamines. The spectral characteristics of fluorophores of so-called "yellow" SIF cells have much in common with the fluorescence spectra of lipofuscin granules. Apparently, in some of cases small cells containing lipofuscin may be identified as "yellow" SIF cells. PMID- 4016232 TI - [Sensory support of tongue movements in the sound-forming process in infants in the lst year of life]. AB - The structural and functional formation of tongue tactile sensory formations were correlated in infants. Heterochronicity was recorded both in build up of receptor formations in different areas of the tongue (tip, body, root) and sensory control of its movements related to sound formation. Receptor formations of the root of the tongue are formed first of all, hence the first sounds that are uttered by infants are primarily velar ones, followed by the appearance of the medio-lingual and later by dorsal sounds. PMID- 4016233 TI - [Mathematical model of vasorenal hypertension]. PMID- 4016234 TI - [Interrelation of the changes in the blood rheological properties and the microcirculatory disorders in the early and late stages of experimental hyperlipoproteinemia]. AB - Experiments were made on rabbit fed an atherogenic diet (0.5 g/kg cholesterol) singly for 15 and 24 h and repeatedly for 3, 9 and 30 days. At early stages of lipid metabolism distress the interrelationship was established between blood rheological disorders and microcirculatory abnormalities. The dependence of the initial reaction of some rheological characteristics on their initial level was marked. PMID- 4016235 TI - [Improved blood flow in the organs and the prevention of thrombus formation with cold]. AB - It has been established that tissue cooling to 15-20 degrees C brings about a short-term spasm of smooth muscles of the intestine, peripheral vessels and of the visceral vessels, replaced by an appreciable spasmolytic effect at the 5th 8th minute of hypothermia. The maximal hyperemia develops by the 15th-20th minute of the cooling and persists over the whole period of the cooling. It is assumed that inhibition of oxidative phosphorylation in the mitochondria of the smooth muscles underlies the spasmolytic action of cold. In addition, cold produces a marked hypocoagulation effect. PMID- 4016236 TI - [Turnover of the amino sugars of erythrocyte and thrombocyte glycoproteins in rats maintained on different carbohydrate diets]. AB - The turnover of erythrocyte and platelet glycoprotein amino sugars in rats fed carbohydrates has been studied. Partial replacement of starch by sucrose results in an almost 3-fold increase in the half-life of erythrocyte glycoprotein amino sugars and in a 2-fold increase in that of platelets as early as 14 days after keeping the animals on carbohydrates. It is concluded that study of dynamic parameters of cell amino sugars can be used for evaluation of the role played by food in metabolic and adaptive reactions both in experimental animals and man. PMID- 4016237 TI - [Inhibitors of reverse serotonin uptake and of specific imipramine binding in human blood plasma]. AB - Human blood plasma contains low-molecular substances that inhibit in a dose dependent manner both high-affinity specific binding of imipramine and reverse serotonin uptake by platelets. Incubation of human blood plasma with alumina was made use of to extract and study these imipramine-like inhibitors. The extract obtained from human blood plasma inhibited imipramine binding and reverse uptake of serotonin with median inhibitory concentrations of 0.18 +/- 0.1 and 0.36 +/- 0.15 mg/ml, respectively. After gel chromatography on Biogel P-2 the elution profile of the extract showed 2 major peaks of reverse serotonin uptake and imipramine binding inhibition and 3 additional peaks of reverse serotonin uptake inhibition, which did not have any considerable effect on imipramine specific binding. It is assumed that endogenous inhibitors of imipramine binding and reverse serotonin uptake are involved in the development of affective disorders. PMID- 4016238 TI - [Changes in the blood system after its extracorporeal irradiation]. AB - One-stage extracorporeal beta-radiation of dog blood in a dose of 6-12 Gy is not followed by the development of radiation after-effects. Favourable changes in the peripheral blood content are marked. Erythrocyte carbohydrates undergo adaptation reconstruction with an increase in the percentage of nucleic acids. Over 7 to 30 days of observation the activity of nonspecific immunity factors such as lysozyme, lytic activity of beta-lysines, and phagocytosis also increases. At the same time the antimicrobial action of penicillin is potentiated. The data obtained can be used for correction of upset immune responsiveness. PMID- 4016239 TI - [Regulatory characteristics of the different components of the mesenteric microcirculatory bed in rats]. AB - Heterogeneous tonic reactions of the different parts of the mesentery microcirculatory bed to intravenous infusions of noradrenaline and their cessation were revealed. It is assumed that venules play a more important role in the organization of blood circulation in the capillaries and arteriolo-venular anastomoses than arterioles. PMID- 4016240 TI - [Effect of the antioxidant dibunol and its combination with phenazepam on the behavior of rats in a conflict situation]. AB - The influence of dibunol, phenazepam used alone and combined on rat conflict behavior and rat blood and brain malonic dialdehyde content was studied. It was shown that dibunol exerts an unmarked anticonflict action that can be removed by bicuculline. Combined administration of dibunol and phenazepam potentiates appreciably the anticonflict effect. This permits reducing the doses of the drugs. The anxiolytic effect of dibunol alone and combined with phenazepam is attended by a decrease in the content of malonic dialdehyde in rat blood and brain, evidence of the reduction of the lipid peroxidation intensity. PMID- 4016241 TI - [Possibilities of using neurotropic agents for preventing the development of aphthous stomatitis]. AB - Aphthous lesions of the oral mucosa were simulated in dogs by common bile duct ligation. In one of the experimental groups, the animals were administered the beta-adrenoblocker obsidan 30 min before operation. Two hours after operation the regions of the oral mucosa mostly affected by aphthous lesions were examined for the content of adrenaline and noradrenaline (NA). The data obtained indicate a significant increase in the content of NA and adrenaline in the oral mucosa 2 h following operation. In animals pretreated with obsidan, the content of catecholamines remained at the level seen in the control group. Therefore, blocking the transmission of nerve impulses to the sympathetic nervous system obsidan interferes with the reflex influence from the involved organs of the abdominal cavity, thereby protecting the oral mucosa tissues from the damage inducing action of high concentrations of NA. PMID- 4016242 TI - [Nonspecificity of the phenomenon of influenza virus phagocytosis by murine macrophages]. AB - Peritoneal macrophage cultures from intact mice and those immune to influenza virus A/PR/8/34 (HON1) were infected with homologous virus or influenza virus A/England/42/72 (H3N2) whereupon virus was isolated from chick embryos. It was established that in intact macrophages, both viruses duplicated similarly. Macrophages immune to virus HON1 equally disintegrated both in homologous virus and heterologous influenza virus H3N2. PMID- 4016243 TI - [Experimental study of the antimutagenic properties of 5-methylresorcinol]. AB - A study was made of the effect of 5-methylresorcinol (5-MR) on mutagenic activity of benzo(a)pyrene (BP) and of the action of gamma-radiation in in-vitro and in vivo systems. The induction of direct gene mutations in Chinese hamster cells V 79 and micronuclei in mouse bone marrow reticulocytes was efficiently suppressed by 5-MR treatment. The antimutagenic activity of 5-MR can be explained by inhibition of free-radical processes. PMID- 4016244 TI - [Influence of anticarcinogenic agents on the transplacental carcinogenic effect of N-nitroso-N-ethylurea]. AB - Experiments on rats were made to study the action of 7 anticarcinogenic substances administered postnatally for a long time (sodium selenite, retinol acetate, phenformin, amber acid, low-molecular polypeptide factors of the thymus, pineal gland, and bone marrow) on the transplacental carcinogenic effect of N ethyl-N-nitrosourea (ENU) The polypeptide factors of the thymus and pineal gland and phenformin inhibited the development of nervous system and renal tumors induced transplacentally by ENU. The rest of the substances did not influence the transplacental carcinogenesis. PMID- 4016245 TI - [Effect of cyclophosphamide on the ganglioside content and profile in metastasizing and nonmetastasizing mammary carcinoma in mice]. AB - The content and profile of gangliosides (Gs) were investigated in metastatic (HMC L) and nonmetastatic (HMC-O) mouse mammary carcinomas before and after cyclophosphamide (CP) treatment. It was shown that the Gs content did not alter markedly during HMC-O growth, whereas in HMC-L, it increased to maximum on day 15 after tumor inoculation and then dropped. CP treatment led to a steady rise in the Gs content in both tumors. The main Gs in HMC-O corresponded to GDIa, GMI, GDIb and hematosides, while in HMC-L, the main Gs at days 9-15 after tumor inoculation corresponded to GDIa (50-65% of total Gs). The action of CP on HMC-O was not accompanied by any essential alterations in the Gs profile, whereas in HMC-L on days 3-6 after CP treatment the relative content of GDIa was significantly lowered and the GMI and hematoside content markedly increased. These findings indicate that there is an obvious relation between the Gs profile and tumor ability to form metastases. PMID- 4016246 TI - [Participation of the lacrimal glands in wound healing processes]. AB - A hypothesis is advanced that nociceptive stimulation activates the functional system of wound healing. Experiments were made to investigate whether the lacrimal glands, which are activated due to pain, are involved in the system of healing. Rat experiments have demonstrated that nociceptive stimulation of the lacrimal glands accelerates the repair of cutaneous wounds by 26 to 30%. Lacrimectomy accompanied by distension of wound rims (up to 26% by the 3d-4th hour) inhibits the rate of healing by 18 to 20%. Intraperitoneal injection of a lacrimal gland extract activates healing in lacrimectomized rats. The data obtained suggest that the lacrimal glands are involved in wound healing. PMID- 4016247 TI - [Reproductive characteristics of the mitochondria in the cardiac myocyte detected by scanning electron microscopy]. AB - Scanning electron microscopy of the left ventricle myocardium of intact rabbit revealed that the mitochondria of cardiac myocytes are formed by division, budding, synthesis de novo from the hyaloplasm, and by "lacing" from channels of the sarcoplasmic reticulum. PMID- 4016248 TI - [Reperfusion damages to the heart in acute transitory coronary failure and their prevention with myophedrin]. AB - Experiments were made on 56 white noninbred male rats with transitory coronary insufficiency (duration of myocardial ischemia 10, 40 and 120 min, the length of subsequent reperfusion 10 and 40 min). It was discovered that there were changes in the ultrastructure of cardiocytes and vessels of the microcirculatory bed both in the area of ischemia and reperfusion and in the distant heart regions, an increase in myocardial cell and microvessel lesions during postischemic reperfusion not only in the area of ischemia but also in distant zones. In addition, a reduction was noted in the degree of ischemic and reperfusion myocardial injury during the prophylactic use of myophedrine. The mechanisms of the protective action of myophedrine in acute transitory coronary insufficiency are discussed. PMID- 4016249 TI - [Effect of masking on interhemispheric and bilateral asymmetry of long-latency auditory evoked potentials]. AB - Considering the effects of noise on the amplitude of long-latent auditory evoked potentials, it is concluded that masking interference diminishes the right hemisphere dominance in the processing of the non-speech acoustic information. The decrease is observed both with the monotic and dichotic delivery of signals and noise. With monotic presentation masking interference also decreases the extent of the lateralization of monaurally delivered information predominantly to the contralateral hemisphere. PMID- 4016250 TI - [Possible role of lipid peroxidation in the pathogenesis of arrhythmias in myocardial infarct]. AB - The effect of myocardial infarction sustained by rats on the resistance of their isolated auricles to H2O2, an inductor of lipid peroxidation (LP), was studied. Atrial resistance to the LP inductor depends on the level of developed tension (DT) and the decrease of DT leads to augmentation of atrial resistance to the arrhythmogenic effect of LP. The experimental myocardial infarction causes appreciable disturbances in the function of automatism of the auricles, 60% of which lose their capability of spontaneous contractile activity. When compared with the control under equal DT, the auricles of the "infarction" series are less resistant to H2O2: the time of arrhythmias and arrests in them are 2.3 times as much as in the control. In infarction, the pretreatment with ionol reduces both the quantity of the auricles which stopped before H2O2 administration and the quantity of the auricles responding by arrhythmia to LP induction. The data point to the possibility of the use of antioxidants for preventing arrhythmias in experimental myocardial infarction. PMID- 4016251 TI - [Comparative morphofunctional research on the individual resistance of animals to hypoxia]. AB - It has been shown in experiments on white male rats that there is a correlation between hypoxia tolerance and the rate of metabolism in brain tissue. Animals with varying tolerance to hypoxia differed also in the acid-base balance of venous blood outflowing from the brain. While adapting to hypoxia animals with high individual tolerance developed the main metabolic changes in the reticular formation and those with low tolerance in the cerebral cortex. During adaptation to hypoxia animals with high and low tolerance had varying changes in acid-base balance. The data obtained allow the conclusion that there is a correlation between the rate of brain tissue metabolism, acid-base balance of jugular vein blood and individual animals' tolerance to hypoxia. PMID- 4016252 TI - [Interrelation of the intracellular oxidation-reduction processes and the organic water balance in experimental peritonitis in rats]. AB - Dissociation of oxidative phosphorylation and the lowering of the respiratory control during oxidation of succinate, alpha-ketoglutarate and pyruvate by hepatocyte mitochondria were observed in rats with experimental fecal peritonitis. The initial increase in the oxidation rate of the substrates enumerated is replaced by inhibition, whose degree is maximal as regards alpha ketoglutarate, being less manifest as regards succinate. In the absence of the manifestations of the total dehydration, the increased water content in liver, skeletal muscle and renal tissues is coupled with relatively high values of the ADP/O and is in a good agreement with the lowering of the respiratory control during alpha-ketoglutarate oxidation. PMID- 4016253 TI - [Effect of food deprivation on the absorption of chick ovalbumin in adult guinea pigs]. AB - A study was made of the effect of complete alimentary fasting of varying duration on barrier permeability of the gastrointestinal tract for chick ovalbumin (OA). Guinea-pigs which fasted for 96, 48 and 12 (control) hours were fed intragastrically 300 mg chick ovalbumin in saline, and after 3 hours immunoreactive OA was measured in blood serum by competitive radioimmunoassay. It was established that fasting of the animals for 96 h led to a significant increase in unchanged food antigen uptake by systemic circulation. The similar increase of OA intake after 48 h of fasting was insignificant. The data obtained can be explained in terms of a decrease in protease activity and inhibition of amino acid uptake by the intestinal epithelium under complete alimentary fasting. PMID- 4016254 TI - [Rate of lymph flow and the protein-electrolyte composition of the lymph from the thoracic duct in experimental acholia]. AB - Experimental acholia was reproduced by applying a biliary fistula to the choledochus in cats for 20 days. It was established that acholia was accompanied by considerable changes in the lymph flow and in the protein-electrolyte composition of the lymph. The rate of the lymph flow in animals with acholia was more than 2 times as decreased as compared with control. The electrolyte and protein shifts in the lymph during acholia were manifested by the reduction in the lymph protein and K+ content. PMID- 4016255 TI - [Dark adaptation of the photoreceptors in the isolated frog retina during induced lipid peroxidation]. AB - The influence of lipid peroxidation (LPO) in isolated frog retina on dark adaptation of photoreceptors was studied. Stimulus-response functions, late receptor potential (LRP) as function of the stimulus light intensity were measured before bleach and in a steady state after dark adaptation. It was shown that accumulation of LPO products influenced dark adaptation in photoreceptors. Based on the displacements of the stimulus-response curves and experimental measurement data on the rate of LRP collapse after retina treatment with strophanthin it is concluded that the most probable mechanism of such an influence lies in a change of photoreceptor plasma membrane permeability. PMID- 4016256 TI - [Brain monoamine oxidase in schizophrenia]. AB - The content of SH-groups and substrate specificity have been studied in purified preparations of monoamine oxidase (MAO) from human brain. It has been shown that both in schizophrenic and mentally normal persons MAO occurs in a partially oxidized state. The enzyme contains 2 SH-groups per 10(5) daltons of protein and deaminates MAO substrates (serotonin, beta-phenylethylamine) along with histamine, diamine oxidase substrate. Reduction of the partially oxidized SH groups of MAO in schizophrenics up to 15 SH-groups per 10(5) daltons of protein (the normal value for human brain MAO) does not eliminate the histamine deaminase activity as is the case in experiments with MAO from the normal brain but, on the contrary, considerably potentiates it. The data suggest certain structural alteration of MAO in schizophrenia. PMID- 4016257 TI - [Possible mechanism of the change in the catalytic properties of brain monoamine oxidase in rats]. AB - An over two-fold decrease in the affinity of mitochondrial MAO to serotonin was found under hyperoxia, hypoxia and cold stress. At the same time serotonin deaminase and glucosamine deaminase activity was detected in the supernatant obtained after precipitation of the mitochondria. The data obtained indicate that the modification of the catalytic properties of MAO is caused both by alteration of the molecular properties of the enzyme and structural derangement of the mitochondrial membranes. PMID- 4016258 TI - [Interaction of liposomes with a varying lipid composition with hepatocytes in vitro]. AB - Interaction of liposomes from egg lecithin, phospholipids and gangliosides of rat liver with rat hepatocyte monolayers was investigated. It was shown that liposomes from phospho- and glycolipids of the liver were bound by rat hepatocytes to a far greater degree than lecithin liposomes. Liver gangliosides increased active endocytosis of liposomes by hepatocytes. Preincubation of hepatocytes with gangliosides reduced the binding of phosphoglycolipid liposomes by those cells. PMID- 4016259 TI - [Hormonal regulation of anabolic processes and of protein utilization efficiency in the early postnatal period]. AB - The levels of thyroid, pituitary and steroid hormones-thyroxine, triiodothyronine and 11-hydroxycorticosteroids in the blood serum, somatotropin in the pituitary, and processes of protein assimilation were studied in rats in the early postnatal period. The highest endogenous production of thyroxine, triiodothyronine and somatotropin was detected in 15-day-old rats. The highest level of protein utilization was detected in 7 to 15-day-old rats, followed by the lowering of the utilization on changing over to definitive nutrition. Endogenous production of the anabolic hormones thyroxine, triiodothyronine and somatotropin was found to correlate with a high level of protein utilization in rats within the first days of life after birth. PMID- 4016260 TI - [Characteristics of the formation of local destructive foci in brain tissues exposed to focused ultrasound]. AB - Local lesions produced in the different brain structures by focused ultrasound were investigated. It was revealed that the blood flow volume velocity had a considerable influence on temperature distribution in the focal area and on the threshold doses and lesion dimensions. Calculation of the lesion diameters on the basis of a purely heat model shows rather good accordance with the experimental data for the large hemispherical cortex and thalamic nuclei with a sufficiently long radiation time. A correlation was found between the subharmonic component of cavitation noise and appearance of the cavities, ruptures, and local hemorrhages located mainly on the boundaries between different cerebral tissues. PMID- 4016261 TI - [Action of thyroxine on the cytochrome content in the brain and liver mitochondria during the postnatal development of rats]. AB - The content of cytochromes c + c1, b and a in brain and liver mitochondria in 7 day-old rats reaches the level seen in adult animals. Administration of L-T4 in a dose of 0.7 micrograms/g rat bw for 4 days before sacrifice results in activation of cytochrome synthesis in both test organs within the first week of the suckling rats' life. On the 20th day of the postnatal period the effect of T4 is seen only in the liver while the brain tissue turns out indifferent to the thyroid hormone. Thus, T4 activates cytochrome biosynthesis in brain mitochondria during the first week of the rats' life, that leads to the acceleration of the functional activity and higher differentiation of the developing brain mitochondria. PMID- 4016262 TI - [Effect of etimizol on instrumental learning in rats]. AB - The action of etimizol on the acquisition of the conditioned reflexes with different complexity and biological significance of reinforcement was studied. The acquisition was performed in a shuttle box and U-shaped maze using food and footshock stimuli. The time interval between administration of etimizol (3 mg/kg) and the onset of learning varied between 0.5 and 3 h in the several series. Etimizol did not facilitate the learning in rats whatever the time of administration and biological modality of reinforcement. It is suggested that the positive effect of etimizol on the memory is related to its influence on the consolidation stage. PMID- 4016263 TI - [Dependence of the effect of vasodilator preparations on the initial distensibility of the vascular bed]. AB - Acute experiments on anesthetized cats under extracorporeal circulation were made to study the effects of papaverine, phentolamine and dihydroergotamine on the blood flow-pressure relations of the vascular bed of the greater circulation. It was shown that the drug-induced change in the vascular resistance were dependent on the perfusion flow and on the initial distensibility of arterial vessels as well. A mathematical simulating model that permits fore-telling alterations in the vascular resistance is described. PMID- 4016264 TI - [Changes in the immunological indices after splenectomy and the reimplantation of splenic fragments in an experiment]. AB - Splenectomized guinea-pigs underwent autotransplantation of splenic fragments into the greater omentum or mesentery of small intestine. Twenty-five to thirty days after operation the animals were infected with S. aureus and then were examined over time before and after infection at different times. Measurements were taken of T lymphocytes, B lymphocytes, lymphocytes with staphylococcal receptors, as well as of the content of neutrophils with IgG Fc-fragment and complement receptors. It was established that in guinea-pigs subjected to splenectomy followed by autotransplantation of decapsulated splenic fragments, the experimental generalized staphylococcal infection took a milder course, which was manifested by an increase in the above immunologic characteristics as compared to animals undergoing splenectomy alone. PMID- 4016265 TI - [Staphylococcal infection in guinea pigs with enhanced delayed hypersensitivity induced by Staphylococcus aureus surface antigens]. AB - A comparative study was made of the relationship between the DHS phenomenon and certain staphylococcal antigens and the intensity of infectious process in sublethal infection of guinea-pigs by Staphylococcus aureus. The protective effect, which was manifested by reduced amounts of staphylococcal colonies in spleen tissues and elevated level of lymphocytes, and neutrophil activation, correlated with DHS induced by surface antigens under study (cell wall, peptidoglycan, protein A). Incomplete combination or certain antigens induced DHS but did not increase the resistance to the following infection. PMID- 4016266 TI - [Evans blue as an adjuvant for enhancing delayed hypersensitivity in an experiment]. AB - A modified method has been elaborated for induction of delayed type hypersensitivity (DH) in CBA mice with the use of Evans blue (EB) as adjuvant. This model permitted studying the mechanism of DH development, establishing the dependence of DH on the dose of EB, the dose and type of protein antigen, and realizing passive transfer of DH with the aid of splenocytes from active synthesized mice. EB is a convenient and effective adjuvant for induction and study of the mechanism of DH development. PMID- 4016267 TI - [Characteristics of the NK cells in Syrian hamsters carrying tumors with varying metastatic and resistance-suppressing activity]. AB - Experiments in vivo and in vitro were made to study the effects of HETR-MLN-8 and HETR tumor cells differing in metastatic ability and inhibition of the natural host resistance to tumor on cytotoxic activity of NK from Syrian hamsters. Marked inhibition of cytotoxicity and ability for interferon activation was detected in NK isolated from tumors (as compared with blood), with that inhibition being far more pronounced in highly malignant HETR-MLN-8 tumors. This may indicate a direct inhibitory action of the tumor or its products on NK cytotoxicity. The in-vitro competition inhibition test yielded results showing that HETR-MLN-8 cells capable of in-vivo inhibition of the natural host resistance to the tumor also display much more demonstrable ability for in-vitro inhibition of NK cytotoxicity as compared to HETR cells. PMID- 4016268 TI - [Effect of methylcobalamin on methotrexate transport in normal and tumorous tissues]. AB - The effect of methylcobalamin on 3H-methotrexate uptake by tumor and normal tissues of mice with mammary adenocarcinoma (Ca-755) was studied. Methylcobalamin stimulated the rate of 3H-methotrexate influx into the tumor and small intestine but did not change its influx into the spleen. The effect was dependent on the dose of methylcobalamin. Comparative analysis of the kinetic differences in 3H methotrexate influx and efflux in tumor and susceptible host tissues revealed the optimal dose of methylcobalamin 0.01 mg/kg to improve the antitumor drug action. PMID- 4016269 TI - [Morphofunctional characteristics of the recovery processes in the resected thyroid of rats]. AB - Histological, electron microscopy and radiometry methods were used to study the time-course of the recovery of the morphological and functional parameters of the rat thyroid after resecting 2/3 of the organ. The signs of thyrocyte regeneration, namely hypertrophy of the cells and ultrastructures, proliferation and formation of new follicles were most pronounced on the 5th day. The increase in the number of C cells, their hypertrophy and proliferation permit attaining the high calcitonin level in the blood serum, reaching a maximum on the 15th experimental day. PMID- 4016270 TI - [Effect of simultaneous partial pancreatectomy on liver regeneration in domestic chickens]. AB - Simultaneous partial pancreatectomy does not change the fundamental mechanisms of reparative regeneration of the chick liver, taking the course of regeneration hypertrophy. Nevertheless it introduces some temporary and quantitative alterations into this process. Later on the connective tissue is formed on the wound surface and infiltration of the resected organ lobe with eosinophilic leukocytes takes place. The wound healing and scar formation are slightly retarded, with the processes of hypertrophy and hyperplasia of the cells being more significant. These events govern more continuous and more intense processes of the regeneration of epithelial structures and the growth of the secretory tubes. The liver weight completely returns to normal toward the end of experiment. Stereological analysis of the regenerating organ shows that this happens largely due to the regeneration growth of the glandular parenchyma because of the activation of proliferative processes and cell hypertrophy. PMID- 4016272 TI - [Structural and functional characteristics of Kupffer cells at different periods of the development of a liver response in mice to injury]. AB - The number of Kupffer cells increased up to necroses and processes of liver regeneration following carbon tetrachloride-induced injury. Mouse Kupffer cells migrated to the necrotic centrolobular zones 48 h after CCl4-induced necroses. During regeneration, Kupffer cells migrated to the sinusoids from the necrotic centrolobular zones. Study of the ultrastructure of Kupffer cells indicates activation of their function during all observation periods. PMID- 4016271 TI - [Morphofunctional restructuring of the nervous system of the lymphoid organs during electrostimulation of the hypothalamus]. AB - The intramural nervous apparatus of rabbit lymphoid organs was examined after 15 and 30 sessions of electric stimulation of the posterior hypothalamus. The function of nerve cells was evaluated by cytophotometry according to the content of catecholamines and acetylcholinesterase (ACE) activity. In the mesenteric lymph nodes, stimulation led to a decrease in the activity of both adrenergic and ACE-containing nerve cells. The spleen demonstrated a reduction in the catecholamine content in the perivascular nerve plexuses, with a simultaneous rise of the catecholamine content in the fibers located in the parenchyma, which evidences inhibition of the neurogenous mechanisms of vasomotor control and possible selective activation of the sympathetic mechanisms involved in the regulation of the immunogenesis. Thymic preparations impregnated with silver salts manifested high argyrophilia of the nerve cells, characteristic of the reactive phase of the destructive process. The problems of the hypothalamic effects on the blood supply and functions of the immune system organs are discussed. PMID- 4016273 TI - [The problem of modelling in pharmacology]. PMID- 4016274 TI - [Multiple recording of electromyograms in a chronic experiment]. AB - The authors describe electromyographic electrodes (EMG electrodes) for recording the activity of several muscles in chronic experiments on cats. An EMG electrode is a loop made of a silver wire 200 micron in diameter and 1.5-2 cm long, to which a flexible copper wire insulated with teflon 300 micron in diameter is soldered. The soldering site is insulated with biologically indifferent material. The EMG electrodes turned out fairly good in numerous experiments. PMID- 4016275 TI - Liquid preservation of human neutrophils stored in synthetic media at 22 degrees C: controlled observations on storage variables. AB - The purpose of this study was to use a chemically defined medium to identify essential substances and optimal conditions for the liquid storage of neutrophils at 22 degrees C. Several commercially available synthetic media were evaluated: L 15, McCoy's 5a, M199, minimum essential medium, Dulbecco's MEM, NCTC135, and RPMI 1640. Proteins, glucose, pH, and neutrophil concentration were systematically studied. Neutrophils were harvested by centrifugal cell separators or phlebotomy, and their maintenance was evaluated by monitoring cell counts, dye exclusion, phagocytosis, bacterial killing, and chemotaxis. Neutrophils stored equally well in all synthetic media except L-15; however, chemotaxis was poorly maintained in synthetic media as compared with autologous plasma. RPMI 1640 was arbitrarily selected as a basal medium to evaluate storage variables. RPMI 1640 supplemented with albumin to a concentration of 1% improved chemotaxis and was equivalent to plasma as a storage medium with regard to the in vitro functions tested. Cohn fractions IV-1, IV-4, and gamma globulin were not effective substitutes for albumin. Glucose is essential for neutrophil storage; its absence from the medium correlated with poor cell function. Optimal glucose requirements depend on the cell concentration. High glucose concentrations were toxic to neutrophils; at 1,000 mg/dL, chemotaxis was depressed by 58%. Glucose utilization was dependent on the initial pH of the medium and on the cell concentration. A wide range of hydrogen ion concentrations was tolerated, and the optimum pH range was 7.2 to 7.8. Cell concentration is an important variable because it affects the pH of the medium as well as glucose utilization. PMID- 4016276 TI - Disparate differentiation in hemopoietic colonies derived from human paired progenitors. AB - We analyzed the differentiation of hemopoietic colonies derived from human paired daughter cells. Candidate progenitor cells were isolated by use of a micromanipulation technique from cultures of My-10 antigen-positive cord blood cells. Then nine to 36 hours later, the paired daughter cells were separated with a micromanipulator and allowed to form colonies in methylcellulose medium containing erythropoietin, phytohemagglutinin leukocyte-conditioned medium, and platelet-poor plasma. The cellular composition of the colonies was determined by differentiating all of the cells of the May-Grunwald-Giemsa-stained preparation. Of a total of 75 evaluable pairs of colonies, 35 consisted of 28 types of disparate pairs revealing nonhomologous lineage combinations. Forty pairs were homologous in lineage expression. However, the proportions of the individual cell lineages were significantly different in the members of some of the homologous pairs. Some pairs revealed significant differences in colony size. These observations are similar to those reported for murine paired progenitors and are consistent with the stochastic model of human stem cell differentiation. PMID- 4016277 TI - Diethylstilbestrol selectively modulates plasma coagulation protein synthesis by the perfused rat liver. AB - The combined effects of orchiectomy and estrogen administration on synthesis of selected hepatic secretory proteins--antithrombin (AT) III, plasminogen, fibrinogen, factor II (prothrombin), factor VII, fibronectin, and albumin--were studied using the isolated rat liver perfused in vitro for ten hours. Male rat liver donors underwent orchiectomy under ether anesthesia and then received 5.0 mg of diethylstilbestrol (DES) by subcutaneous pellet implantation or a placebo pellet; 14 days later the livers were extracted and perfused in vitro for ten hours. In DES experiments, 1.0 mg of DES was also added directly to the liver perfusate at the outset. Pretreatment with DES resulted in significant increases in cumulative synthesis of factors II (65%) and VII (76%) and significant reduction in cumulative synthesis of both antithrombin III (20%; P = .03) and plasminogen (27%; P less than .01) compared to control perfusions, but synthesis of fibrinogen, fibronectin, and albumin was not significantly affected by addition of the hormone. Plasma samples collected from rat liver donors that had received DES showed similar effects on protein concentrations: significant decreases in concentration of plasminogen and antithrombin III were apparent with no significant changes in concentrations of fibrinogen, fibronectin, or albumin. In additional perfusions, "dose-response" experiments were conducted in which rat liver donors received a subcutaneous DES pellet of 0.5, 5.0, or 50 mg. Synthesis of plasminogen in this group of perfusions was progressively decreased as the concentration of DES administered to the rat liver donor increased. Synthesis of AT III was reduced to the same degree by 5.0 or 50 mg of DES, both being substantially lower than the 0.5-mg experiments. Concentrations of these two proteins in plasma samples from rat liver donors showed changes quite similar to those seen in perfusion experiments; however, plasma fibrinogen concentrations were not different among the three groups of rats. PMID- 4016279 TI - Growth and cytogenetic characteristics of bone marrow colonies from patients with 5q-syndrome. AB - Early erythroid precursor cells and myeloid progenitor cells (CFU-GM) from four patients with 5q-syndrome were cultured in order to study the in vitro growth patterns and to determine the clonal origin of this hematologic disorder. Cultures of CFU-GM exhibited normal colony growth, while erythroid progenitor cells demonstrated a marked decrease or absence of colony growth. Chromosomal studies indicate the 5q-chromosome is present in both hematopoietic progenitor cells, suggesting that the syndrome is an acquired clonal disease arising from a pluripotent hematopoietic stem cell. Follow-up cytogenetic studies reveal a decrease in the number of normal metaphases. This finding is consistent with reports that emphasize the slowly progressive nature of this malignant stem cell defect. PMID- 4016278 TI - Evaluation of covalent antisickling compounds by PO2 scan ektacytometry. AB - The ektacytometer, a device to measure erythrocyte flexibility, has been used to evaluate antisickling agents that covalently modify hemoglobin S (HbS). The instrument has been adapted to produce a continuous gradient of oxygen pressure in the measuring cuvette, which permitted the rapid determination of sickle cell rigidity over the complete oxygenation range. Inspection of curves allows classification of the compounds according to their mode of action: altering oxygen affinity or increasing deoxy-HbS solubility. Reagents that modify amino groups, thiols, and histidine, as well as a crosslinking agent, were examined. The method directly evaluates deoxygenated cell deformability rather than cell shape. Many of the compounds that are effective in preventing the morphological sickling of deoxygenated sickle cells do not necessarily restore cell deformability. The method also readily detects membrane damage brought about by covalent agents that nonspecifically derivatize membrane proteins. Cystamine and pyridoxal appear to improve deformability in deoxygenated SS cells at concentrations that do not damage the membrane. This method, which examines the intact cell, fills a gap in the available experimental techniques for drug evaluation, between studies of isolated hemoglobin and in vivo studies. PMID- 4016280 TI - Estradiol and progesterone receptors in breast cancer: prognostic value after relapse. AB - The prognostic significance of estradiol (ER) and progesterone receptors (PgR) for survival from relapse has been studied in two groups of breast cancer patients: group 1, 35 patients in whom receptor levels were measured at the time of mastectomy; group II, 49 patients in whom receptor levels were measured at the time of recurrence. ER+ (greater than 10 fmoles/mg) patients had a better survival from relapse than ER- patients. High levels of PgR (greater than 50 fmoles/mg) had a prognostic significance only in group II patients. PMID- 4016281 TI - The relationship between estrogen receptors in primary and secondary breast carcinomas and in sequential primary breast carcinomas. AB - A review of over 2000 patients who had estrogen receptors (ER) assayed in the primary breast carcinoma identified 48 cases in whom a subsequent second primary breast carcinoma or concurrent or recurrent secondary tumour had been tested for ER status. The relationship between the ER in the two specimens was as follows: Of 14 concurrent primary and secondary breast carcinomas the ER concentration was the same in 11 cases; in 1 case it was significantly higher in the primary tumour, in 2 others the reverse was observed. There was no major discordance in ER status. In 14 sequential carcinomas (after an average disease free time of 21 months), 12 pairs had identical ER status. There was major discordance of ER status in 2 cases where the secondary tumours contained ER while the primary carcinoma did not. The ER concentrations in the primary and the secondary carcinomas were comparable in 8 cases, while 3 and 5 cases had significantly higher or lower concentrations respectively in the sequential secondary tumour. In 20 cases where breast cancer developed in the contralateral breast (after an average disease-free interval of 27.7 months), essential concordance of ER status was observed in 15 of 20 sequential carcinomas. In 5 patients the first carcinoma was ER- and the second ER+; in one additional patient the first carcinoma was ER +/- and the second ER-. The ER concentrations differed significantly in 14 of the 20 bilateral carcinomas. The literature on estrogen receptor variation in breast carcinoma was reviewed. PMID- 4016282 TI - Cytosol and nuclear estrogen receptors (occupied and unoccupied sites) and progesterone receptors in human breast cancer. AB - Estrogen and progesterone receptor concentrations in cytosol and nucleus were measured in 21 primary breast cancer tumors. Twelve out of the 21 tumor samples were cytosol estrogen receptor positive, 8 of which contained only unoccupied estrogen binding sites in the cytosol, but 2 of the 9 'estrogen receptor negative' samples did contain cytosol binding sites already occupied by endogenous hormone. Four other 'estrogen receptor negative' tumors only showed nuclear binding sites. Only 3 of the 12 'estrogen receptor positive' tumors also contained progesterone receptors. All of these tumors also had estrogen receptor in the nucleus. However, three of the 17 'progesterone receptor negative' samples had progesterone receptor only in the nucleus. The present data indicate that 3 possible classes of 'false negative' tumors can be encountered: estrogen receptors occupied by endogenous hormone, tumors containing only nuclear estrogen receptors, and tumors having only nuclear progesterone receptors. Measurement of nuclear estrogen receptor together with the progesterone receptor provides further information on whether the estrogen receptor system is not only present but also functional, and should be of value in the prediction of hormone dependent breast cancer. PMID- 4016283 TI - Seasonal variation in breast cancer detection: correlation with tumour progesterone receptor status. AB - A significant circannual variation of the month in which patients detect the first sign or symptom of tumour has been defined in 1413 patients with breast cancer. The months of highest detection were in the late spring-early summer, and lowest detection was in late autumn-early winter. Analysis of subgroups indicates that this cyclic trend was most significant in younger women with small or moderate-sized tumours containing steroid hormone receptors, particularly progesterone receptors. It seems likely that this variation is related to the effect of cyclic hormonal changes on tumour growth, possibly mediated through the pineal. PMID- 4016284 TI - Weight gain during adjuvant chemotherapy for breast cancer. AB - Weight gain during adjuvant chemotherapy has been reported by several authors. Because increased body weight at diagnosis is associated with an increased risk of disease recurrence, we have assessed the prevalence of weight gain in a series of patients receiving adjuvant treatment, as well as the association of weight gain with type of treatment and risk of recurrence. We first assembled an inception cohort of 237 patients who had all undergone pretreatment evaluation and treatment at one institution, and had already been followed for at least 12 months. Body weight at the start and completion of treatment was recorded, as was type of treatment and status at last followup. Ninety-six percent of patients gained weight during treatment and none lost weight (mean increase 4.3 kg). Weight gain was strongly associated with treatment, and was least in patients receiving single agent chemotherapy, greatest in patients treated with ovarian ablation and prednisone, and intermediate in those receiving combination chemotherapy. There was no association between weight gain and disease recurrence. PMID- 4016285 TI - Family history and bilateral primary breast cancer. AB - The prevalence of a family history of breast cancer was established in 54 women with bilateral primary breast cancer and 208 women with unilateral disease. Women with bilateral disease had significantly greater prevalence of family history than women with unilateral breast cancer (P less than 0.01). Compared with the unilateral cancers, a significantly greater proportion of bilateral cancers had first degree affected relatives (P less than 0.05). Moreover the affected relatives of probands with bilateral disease showed a significantly higher prevalence of bilateral breast cancer compared with the relatives of women with unilateral disease (P = 0.04). The findings suggested that bilateral disease was a characteristic of familial breast cancer. PMID- 4016286 TI - Increased serum corticosterone levels in triorthotolyl phosphate-treated chickens. PMID- 4016288 TI - Resolution and biological activity of the optical isomers of 3-tert-butylphenyl sec-butylcarbamate. PMID- 4016287 TI - Inhibition of TCDD-induced lipid peroxidation, glutathione peroxidase activity and toxicity by BHA and glutathione. PMID- 4016289 TI - Tritium toxicity: age-dependent radiosensitivity of mouse testes. PMID- 4016290 TI - Dissipation of 1,2-dibromo-3-chloropropane (DBCP), cis-1,3-dichloropropene (1,3 DCP), and dichloropropenes from soil to atmosphere. PMID- 4016291 TI - Organochlorine residues in animals from three Louisiana watersheds in 1978 and 1979. PMID- 4016292 TI - Cytopathological and numerical changes in haemocytes of Periplaneta americana after treatment with malathion. PMID- 4016293 TI - Modification of aerosol size distribution by complex electric fields. PMID- 4016294 TI - Effect of metals and other inorganic ions on soil microbial activity: soil dehydrogenase assay as a simple toxicity test. PMID- 4016295 TI - Metabolism of aldrin by the freshwater planarian Phagocata gracilis. PMID- 4016296 TI - Evidence for polynuclear aromatic hydrocarbons in the diet of bottom-feeding fish. PMID- 4016297 TI - Inorganic chemical composition of trout food pellets and alfalfa used to sustain Daphnia magna Straus. PMID- 4016298 TI - Toxicity and accumulation of copper and cadmium in the alga Scenedesmus obliquus LH. PMID- 4016299 TI - Gender disturbance in children. An interim clinical report. PMID- 4016300 TI - Sex therapy today. PMID- 4016301 TI - [Surgery of strabismus]. PMID- 4016302 TI - [ETO, nonspecific stimulant as therapy for degenerative diseases of the eye]. PMID- 4016303 TI - [Hypermetropia and esotropia. Apropos of 600 cases]. PMID- 4016304 TI - [Importance of the fold in surgery of the upper eyelid]. PMID- 4016305 TI - [Simplified wide-field endothelioscopy]. PMID- 4016306 TI - [Technics for identifying morphologic features observed during specular microscopy of the cornea]. PMID- 4016307 TI - [Specular microscopy and anterior chamber implants]. PMID- 4016308 TI - [Permanent wearing of gas-permeable hard contact lenses. Several clinical illustrations]. PMID- 4016309 TI - [Diagnostic elements in hamartoma of the retina and the pigment epithelium]. PMID- 4016310 TI - [Continuous internal packing with air in the treatment of certain retinal detachments]. PMID- 4016311 TI - [Cataract after vitrectomy through the pars plana and silicone oil injection]. PMID- 4016312 TI - [Indications for vitrectomy in ischemic diabetic retinopathy. Apropos of 570 cas]. PMID- 4016313 TI - [Results of vitrectomy in diabetic retinopathy. A propos of 570 cases]. PMID- 4016314 TI - [Vitrectomy to prevent retinal detachment in aphakia. Hyalitis, perforating injuries, diabetes, myopia, in the absence of vitreous hemorrhage]. PMID- 4016315 TI - [Surgical treatment of macular epiretinal membranes]. PMID- 4016316 TI - [Choroidal detachment after surgery for retinal detachment]. PMID- 4016317 TI - [Velocimetric analysis of posterior ciliary arteries by the pulsed-Doppler method]. PMID- 4016318 TI - [New considerations on choroidal circulatory dynamics]. PMID- 4016319 TI - [Treatment of malignant melanoma of the choroid]. PMID- 4016321 TI - [Ionizing radiation in the treatment of melanomas of the choroid]. PMID- 4016320 TI - [Conservative treatment of melanomas of the choroid]. PMID- 4016322 TI - [Unusual aspects of choroidal insufficiency]. PMID- 4016323 TI - [Uveal leprosy in Iran]. PMID- 4016324 TI - [Cavernous hemangiomas of the choroid. Clinical and therapeutic review of 13 cases]. PMID- 4016325 TI - [Fluorescein angiography of several diseases of the choroid in the dog]. PMID- 4016326 TI - [Occlusion of the posterior ciliary arteries after surgery for retinal detachment]. PMID- 4016327 TI - [The heavy eye syndrome]. PMID- 4016328 TI - [Acute sectoral choroid ischemia (triangle syndrome)]. PMID- 4016329 TI - [Chorioretinal malformations in an unknown oculo-cerebral syndrome]. PMID- 4016330 TI - [Geographic choroiditis. Prognostic and physiopathologic significance of disappearance of the hyperfluorescent border]. PMID- 4016331 TI - [Acute choriocapillary occlusions of inflammatory origin. Apropos of 5 cases]. PMID- 4016332 TI - [What does evaluation of uveitis mean in 1984?]. PMID- 4016333 TI - [Results of early treatment of peripheral facial paralysis using ultrasound]. PMID- 4016334 TI - [Baby vision: the preferential looking technic in the detection of vision abnormalities in the infant]. PMID- 4016335 TI - [Evolution of early diabetic retinopathy. Clinical and angiographic study]. PMID- 4016336 TI - [Absolute light threshold in senile cataract in myopic and emmetropic eyes]. PMID- 4016337 TI - [Atopic cataract]. PMID- 4016338 TI - [Determination of the iron content of the normal lens and the cataracted lens]. PMID- 4016339 TI - [The electroretinographic score. Significance and application, especially for preoperative prognosis (media problems in particular]. PMID- 4016340 TI - [State of the crystalline lens in 180 eyes treated by vitrectomy in the pars plana]. PMID- 4016341 TI - [Diagnostic pitfalls of congenital paralysis of the 3d cranial nerve]. PMID- 4016342 TI - [Our experience with anterior implant with angular support. Results of 350 cases]. PMID- 4016343 TI - [Preoperative detumescence of the vitreous]. PMID- 4016345 TI - [Correction of aphakia with an intraocular implant. Can it be considered a routine operation?]. PMID- 4016344 TI - [Site of implantation as a factor in inflammation of the iris]. PMID- 4016346 TI - [Association between cataract and glaucoma. Clinical and therapeutic aspects]. PMID- 4016347 TI - [Licorne eyeglasses. Pre- and postoperative treatment of strabismus]. PMID- 4016348 TI - [Myopic keratomileusis]. PMID- 4016349 TI - [Our experience with surgical treatment of idiopathic congenital nystagmus in 130 surgical cases from 1973 to 1983]. PMID- 4016351 TI - [Fibrous structure of the human vitreous body]. PMID- 4016352 TI - [Acupuncture in ophthalmology]. PMID- 4016350 TI - [Results of 200 trabeculoretractions with 1 year follow-up]. PMID- 4016353 TI - [Severe syndromes of ocular dryness: their treatment by inserts]. PMID- 4016354 TI - [Unfavorable prognostic elements in occlusions of the central retinal vein of the edematous type]. PMID- 4016355 TI - [Clinical significance of bitemporal paralysis of the pupillary sphincters]. PMID- 4016356 TI - [Sector relays----surgery----sectors]. PMID- 4016357 TI - [Retinoblastoma: clinical and therapeutic study]. PMID- 4016358 TI - ["Keratocorrection" or corrective surgery of astigmatism]. PMID- 4016359 TI - [Application of the torticollimeter to strabology]. PMID- 4016360 TI - [Athermic procedure in the surgical treatment of retinal detachment? Concept of minimal retinopexy]. PMID- 4016361 TI - [Experimental study of the toxicity of adrenaline on the corneal endothelium. Application to extracapsular cataract surgery]. PMID- 4016362 TI - [Postoperative electrophysiologic and sensory correlations in 121 cases of convergent strabismus in children]. PMID- 4016363 TI - [Arterial pedicles of the oculomotor muscles. Anatomic study of 70 orbits]. PMID- 4016364 TI - [Angiography on dia-contact]. PMID- 4016365 TI - [Visual evoked potentials induced by pattern reversal with color stimulation in multiple sclerosis]. PMID- 4016366 TI - [Can visual evoked potentials be of prognostic value in the alcoholic?]. PMID- 4016367 TI - [Experimental choroidal ischemia by vortex embolization in the monkey]. PMID- 4016368 TI - ["Indirect" corneal trepanation]. PMID- 4016369 TI - [Cuppers fadenoperation on the superior rectus. Apropos of 80 cases]. PMID- 4016371 TI - [Application of the loop technic in the surgical treatment of esotropia]. PMID- 4016370 TI - [Physiologic and semeiologic value of the lobular appearance of the choroid angiogram]. PMID- 4016372 TI - [The operation of myectomy of the inferior oblique]. PMID- 4016373 TI - [Treatment of pseudoparalysis of the inferior oblique]. PMID- 4016374 TI - [Surgery on the oculomotor muscles and binocular motor function]. PMID- 4016375 TI - [Dynamic study of eye movements before and after surgery for strabismus]. PMID- 4016376 TI - [Papilledema in the primary empty sella syndrome]. PMID- 4016377 TI - [Use of the Yag pico- and nanosecond laser in ophthalmology]. PMID- 4016378 TI - [Surgery of strabismus in the adult]. PMID- 4016380 TI - [Electron-micrographic study of 31 explanted artificial crystalline lenses]. PMID- 4016379 TI - [Bridging the internal rectus muscle in surgery for strabismus in the child]. PMID- 4016381 TI - [Surgery for strabismus complicating cranio-facial abnormalities]. PMID- 4016382 TI - [Results of surgical treatment of strabismus using the technic of desagittalization of the obliques]. PMID- 4016383 TI - [28 years of recession of the inferior oblique]. PMID- 4016384 TI - [Anteroposition or disinsertion of the inferior oblique. Which to choose?]. PMID- 4016385 TI - [Results of plication of the superior oblique]. PMID- 4016386 TI - [Results of strabismus surgery using Gobin's technic]. PMID- 4016387 TI - [Results of the fadenoperation in our cases of convergent strabismus]. PMID- 4016388 TI - [Value of "loop" surgery using the Weiss-Gobin technic]. PMID- 4016389 TI - [Treatment of congenital esotropic strabismus by the Gobin loop technic. Apropos of 38 cases]. PMID- 4016390 TI - [X-ray computed tomographic demonstration of the effects of tendon lengthening by the Focosi method]. PMID- 4016391 TI - [Results of treatment of strabismus in the premature infant: preliminary study]. PMID- 4016392 TI - [The accommodative component after classic surgery for partially accommodative strabismus]. PMID- 4016393 TI - [Binocular vision after surgical correction of accommodative strabismus]. PMID- 4016394 TI - [Multicenter analysis of the results of surgery for convergent strabismus]. PMID- 4016395 TI - Surgical drainage. AB - The principle factor governing the efficacy of a drain is the tissue reaction to the constituent material. This was appreciated during the early development of drainage. Modern materials have been available for more than 20 years but have escaped sound clinical evaluation. In abdominal surgery there is virtually no evidence to support routine intraperitoneal drainage especially with latex rubber unless it is intended to create a fibrous tract as with T-tube drainage of the biliary tree. When drainage is used either static symphonage (Fig. 7), low pressure suction or sump suction with a bacterial air inlet filter should be employed. Silicone rubber (Silastic) tubes are the preferred material. In the parietes closed suction drainage is safe and has achieved a sound reputation for improving healing where serosanguinous oozing is expected. High pressure suction is probably the most effective system. Because of the risk of infection, open drainage systems should, in general, be avoided, especially where a prosthesis is present. Finally, if in doubt, all surgeons should recall the words of Halsteads in 1898 "No drainage at all is better than the ignorant employment of it" rather than the advice of Lawson Tait. PMID- 4016396 TI - Intravenous regional anaesthesia. AB - The technique of intravenous regional anaesthesia (IVRA) has failed to gain general acceptance among anaesthetists, who are divided into those who never use it, preferring more specific local anaesthetic blocks, and those who would recommend it as the technique of choice for some procedures. Numerous large series have been published, attesting to its general safety, but intermittent accounts of serious side effects and more recent reports of fatalities have called the technique into question, so that a reassessment seems timely. PMID- 4016397 TI - Induced hypotension. AB - The use of induced hypotension in the hands of a competent anaesthetist combined with the careful technique of a surgeon skilled in operating under these conditions can aid surgical access, improve delineation of pathology, and reduce levels of blood loss, all of which are to the advantage of the patient. These advantages should encourage surgical and anaesthetic teams to become accomplished exponents of the art. PMID- 4016398 TI - High frequency ventilation. AB - What is high frequency ventilation? Is it useful or just another transatlantic fad? Apart from appearing to break all the rules of physiology, this technique has definite advantages over conventional ventilation in certain areas and great potential in others. PMID- 4016399 TI - Treatment and justice. AB - Support for the belief that criminal behaviour was amenable to treatment served different purposes: for developing psychiatry it offered a module of power to be exploited whereas for the State it was a convenient disguise for the infliction of pain which was the real intention of punishment. Having served its purpose the treatment approach is being abandoned in favour of a philosophy of just deserts which is more acceptable in the present political climate. PMID- 4016400 TI - Male homosexuality and sexual problems. AB - Homosexual men are increasingly seeking help with sexual problems. A few seek to change their orientation and there is evidence that, for some people at least, this is possible. However the major reason for seeking help is sexual dysfunction which is treatable in homosexual men in the same way as in heterosexuals. PMID- 4016401 TI - Private practice: financial records. PMID- 4016403 TI - Mentally ill doctors. PMID- 4016402 TI - Malignant melanoma. PMID- 4016404 TI - Diplopia. AB - Diplopia may be a presenting symptom of a wide variety of ocular and neurological conditions. Careful questioning and examination will reveal the cause in many cases and may save the patient much unnecessary and expensive investigation. PMID- 4016405 TI - Visual field defects. AB - The detection and analysis of visual field defects allows the practitioner to examine some functions of the central nervous system at the bedside. Cerebrovascular accidents and temporal lobe tumours can be diagnosed easily, as can pituitary lesions. PMID- 4016406 TI - Whole body computed tomography in cancer management. AB - Whole body computed tomography (CT) can provide information which was previously impossible or difficult to obtain about the presence and extent of tumours. However, the technique is still not generally available and many patients with cancer are investigated and sometimes treated in hospitals without CT facilities. The purpose of this brief review is to provide a summary of the value of CT in oncology, highlighting its strengths and weaknesses, so that clinicians with only a general interest in the subject may be aware of the major indications for its use in the assessment of malignant disease. PMID- 4016407 TI - The phases and stages of labour. AB - During recent decades the understanding and practice of obstetric care have evolved at a rapid pace. Consequently definitions that have promoted the principles of practice have had to be greatly modified or discarded. My thesis is that the time has come for the concepts of phases and stages of labour to be abandoned on the grounds that they now retard, rather than advance, progress in the care of the labouring woman. PMID- 4016408 TI - The perinatal database: content and collection. AB - Recent advances in computer technology provide improved means for the collection of information for the perinatal database. They depend principally upon online entry via a computer terminal which allows immediate checking of the data input. The availability of such effective procedures for information gathering demands a careful review of the purposes, content, and structure of a computerized perinatal questionnaire. PMID- 4016409 TI - Reye's syndrome. AB - Reye's syndrome, an uncommon childhood encephalopathy of uncertain aetiology, is an important cause of mortality and permanent handicap. Since its recognition treatment has changed, current management focusing upon prevention or control of raised intracranial pressure. Prognosis is radically improved by early recognition and prompt transfer to a specialist centre. PMID- 4016410 TI - Thrombotic vascular disease. AB - Thrombovascular disease represents one of the most important causes of morbidity and mortality. Although coronary artery disease attracts most attention, other types of vascular disease also make a substantial contribution to the overall statistics. These include microangiopathy, particularly in relation to diabetes mellitus, and deep vein thrombosis and its associated complications of pulmonary embolus and postphlebitic syndrome. PMID- 4016411 TI - Infection and blood transfusion. PMID- 4016412 TI - The psychiatrist in court. AB - Psychiatric evidence may be required on a variety of issues in different courts. Psychiatrists in court face ethical dilemmas, and psychiatric evidence can be misused. Good preparation for cross-examination and a proper understanding of the limits of professional expertise are needed. PMID- 4016413 TI - Informed consent. PMID- 4016414 TI - Private practice: practice accounts. PMID- 4016415 TI - Strabismus in childhood. AB - Strabismus is a common childhood disorder which is underdiagnosed and undertreated. A detectable squint at any age is abnormal and should be investigated to exclude significant ophthalmological or systemic disease. Early detection and treatment will enable normal and near-normal binocular functions to be achieved in many children. PMID- 4016416 TI - Reconstruction of the ala of the nose using a composite free flap from the pinna. AB - A new method of reconstruction of the nasal ala is described using a composite free flap taken from the anterior part of the pinna, based upon the superficial temporal vessels. Forty cadaver dissections have been performed to assess variations in vascular anatomy and a direct branch of the superficial temporal artery was found in 90% of subjects. The flap has been used successfully in two cases. PMID- 4016417 TI - Surgical approaches to block dissection of the inguinal lymph nodes. AB - Block dissection of the inguinal lymph nodes is associated with a high incidence of complications, the most frequent of which are related to wound healing. To determine the optimal surgical approach, a review of our experience over the last 10 years was undertaken. Fifty inguinal lymph node dissections are presented. The patients were divided into four groups according to the surgical incision used. The duration of hospital stay and incidence of complications were compared. We conclude that the optimal surgical approach is an elliptical incision removing a 4 cm width of skin over the inguinal nodes. Incisions that did not sacrifice at least a 4 cm width of skin had an inordinately high complication rate and a prolonged hospital stay. Approaches to wound closure, the management of bulky disease and primary lesions in continuity with the groin, and the use of adjunctive measures to reduce morbidity are discussed. PMID- 4016418 TI - Levator palati and palatal dimples: their anatomy, relationship and clinical significance. AB - To achieve the best results in cleft palate repair it is necessary to be aware of the normal anatomy. In a series of cadaver dissections, the levator palati muscle was found to occupy the intermediate 40% of the length of the soft palate. This normal distribution should be the aim at cleft palate repair. Observation of the oral surface of the palate during production of the sound "Ah" reveals palatal dimpling. This has been observed in many normal and cleft palate subjects. The dimpling has been reproduced in cadavers by levator palati traction and been found on dissection and serial histological section to correspond to the levator insertion. PMID- 4016419 TI - Musculus uvulae and levator palati: their anatomical and functional relationship in velopharyngeal closure. AB - The morphological relationship between the musculus uvulae and levator palati muscles and their importance in velopharyngeal closure was studied in cadavers by simulation of levator action, palate serial section and dissection, and in various subjects by nerve stimulation and blockade. These studies support the cardinal importance of the levator muscles in velopharyngeal closure. The significance of musculus uvulae activity is less clear. While lesser palatine nerve stimulation evoked a response from the musculus uvulae, a nerve block produced no detrimental effect on speech or nasendoscopic appearance in normal subjects. PMID- 4016420 TI - The Pierre Robin syndrome reassessed in the light of recent research. AB - For many years clinicians have known the coincidental presentation of micrognathia, glossoptosis and cleft palate as the Pierre Robin syndrome. In conferences in 1974 and 1975 the term "Anomalad" was introduced which by definition is a primary malformation with superimposed secondary structural changes and the Pierre Robin syndrome became known as the Robin Anomalad. The concept was based on experimental observations available at that time. However, since that date further studies have demonstrated that administration of drugs to pregnant female rodents can produce coincidental failure of normal development of both mandible and palate. In the light of this work a critical review is made of the evidence upon which the mechanistic view of the condition evolved and an alternative hypothesis developed. From animal experimentation it can be argued that the nature of the condition is not mechanical and is more likely to be metabolic. Indeed, confirmatory evidence in man has recently been presented from Finland. If this is the case it may be erroneous to consider the Robin malformations as an "Anomalad" and mandibular maxillary agenesis would probably be a more accurate term. PMID- 4016421 TI - The use of a vomerine flap for palatal lengthening: the modified Nagpur technique. AB - Considerable significance is attached to velar length in achieving velopharyngeal closure. A technique of palatal lengthening using a vomerine flap is described and its relative merits compared with other methods are discussed. PMID- 4016422 TI - Healing following full thickness excision of human palatal mucosa. AB - Healing was observed for 6 months following excision of full thickness normal adult human palatal mucosa (approx 12 mm X 10 mm) to measure the degree of wound contraction and determine if rugae would regenerate. Measurements of plaster models showed stretching and displacement of soft tissue not involved in the original would toward the centre of the wound from 6 weeks postoperatively. The distance between the incisive papilla and the most posterior ruga on the side of operation reduced by 2.2 mm and the first ruga on the opposite side was stretched in length by 0.9 mm. A fragment of superficial bone (approx 10 mm X 7 mm) sequestrated at 5 weeks, epithelialisation was complete by 8 weeks but the rugae did not reform at all. PMID- 4016423 TI - Cryptotia: our classification and treatment. AB - Our classification of cryptotia is based on recognition that the deformity is the result of an anomaly of the intrinsic transverse and oblique auricular muscles. Our treatment, in the first instance, is a non-surgical correction. This should be started early, if possible in the first 6 months of the baby's life. Even in the case of older children, success can sometimes be achieved and a non-surgical correction should be considered first. If non-surgical management fails the deformity can be corrected surgically by dividing the muscle fibres that produce the anomaly of the external ear through a small incision. Our new surgical approach involves moving the available skin in the region of the inferior cephalo auricular sulcus to the superior part where skin is needed by a rotation flap. This operation has several advantages. PMID- 4016424 TI - Shoulder function following the loss of the latissimus dorsi muscle. AB - A study of shoulder function was carried out in a group of 19 male patients who had their latissimus dorsi muscle removed as a free flap. A control group was examined to obtain data for the normal range of movement and power at the shoulder. Only a few patients had any subjective impairment of shoulder function; 13 of our 19 patients had a complete range of movement at the shoulder. There was no significant difference in power between the patient group and the control group when dominant and non-dominant sides were considered separately (p greater than 0.05). Patients who had surgery carried out more recently and patients with a scar contracture had a significantly higher disability score. The latter group also had a greater deficit in range of movement at the shoulder (p less than 0.05). Most patients encountered no difficulty whatever with their occupational and sporting activities. Our results support the view that the latissimus dorsi muscle is totally expendable and that there is no significant functional loss at the shoulder, either in casual or in forceful activities. PMID- 4016425 TI - Injury to the brachial plexus resulting from shoulder positioning during latissimus dorsi flap pedicle dissection. AB - A case is described of brachial plexus injury, noted after an ipsilateral latissimus dorsi free transfer. The mode of injury is discussed and a simple method of prevention is suggested. PMID- 4016426 TI - The development of a dynamic model for microvascular research and practice using human placenta: a preliminary report. AB - Human placenta has been investigated in an attempt to develop a non-animal model for microvascular research and practice, with a dynamic artificial circulation. Initial work has been encouraging and further development is in progress. PMID- 4016427 TI - Raising the radial artery forearm flap: the superficial ulnar artery "trap". AB - An anomalous superficial ulnar artery was encountered during the raising of a free radial artery forearm flap. A description is given of the anatomy of the ulnar artery, its variation and vulnerability during the raising of a forearm flap. PMID- 4016428 TI - Acute ischaemia of the hand resulting from elevation of a radial forearm flap. AB - Acute ischaemia of the hand following the elevation of a radial forearm flap despite a satisfactory preoperative Allen's test is reported. Circulation to the hand was restored by a vein graft. The importance of ensuring that peripheral circulation is adequate after raising such a flap is stressed. PMID- 4016429 TI - The use of de-epithelialised cross-finger flaps for dorsal finger defects. AB - A de-epithelialised cross-finger flap procedure for repair of dorsal finger defects is described. It is safe and simple and is considered to have distinct advantages over other available methods of flap repair of the dorsum of the finger. These advantages are discussed. PMID- 4016430 TI - L-plasty technique in the repair of split ear lobe. AB - A new and effective technique for the repair of split ear lobe is presented and the mechanism of acquired cleft ear lobe from the wearing of earrings is discussed. PMID- 4016431 TI - Congenital accessory ectopic eyelid: case report. AB - An extremely rare case of congenital accessory ectopic eyelid associated with an oblique facial cleft is reported. The clinical features, histological findings and morphogenesis are briefly described. PMID- 4016432 TI - Malignant melanoma in childhood. AB - Only two cases of malignant melanoma in childhood have previously been reported in this Journal (Olbourne and Harrison, 1974; Keall et al., 1981). The report describing 31 cases in the Manchester area (Pratt et al., 1981) indicates that this condition may be more common in this country than previously supposed. A case of malignant melanoma arising in a mole in a 23 month male child is reported. A review of the literature shows that there are no survival figures for cases without metastasis but at present there is no reason to suspect that the disease is any less aggressive than in adults. It cannot be stressed too often that any mole with rapid growth, ulceration, bleeding with minimal trauma and change in colour should be biopsied urgently irrespective of the age of the patient. PMID- 4016433 TI - British Microsurgical Society meeting. London, 17-18 September 1984. Abstracts. PMID- 4016434 TI - The importance of the lymphatic system. PMID- 4016436 TI - Understanding the Italian Experience. AB - The "Italian Experience" in closing down mental hospitals has been highly praised by some British observers, who have seen lessons for Britain in the development of community care. However, it has been the subject of heated debate in Italy- and the policy is now to be reversed by law. Two questions arise: why have the claims been exaggerated? And why have they found such ready and uncritical acceptance in Britain? PMID- 4016435 TI - Proceedings of the British Pharmacological Society. Cardiff, 10th-12th April, 1985. Abstracts. PMID- 4016437 TI - Schizophrenia with good and poor outcome. III: Neurological 'soft' signs, cognitive impairment and their clinical significance. AB - Fifty-six patients with RDC schizophrenia (42) or schizoaffective disorder (14), of two to 20 years' duration, were assessed for neurological 'soft' signs and cognitive impairment when in a stable condition--the 'outcome'. Neurological dysfunction (46% of 50 examined patients) was associated with a history of developmental abnormalities, but was unrelated to outcome, psychiatric symptoms, or treatment. Deficits in particular cognitive fields were related to two independent factors: overall severity of residual psychiatric disorder (outcome) and neurological dysfunction. There was no relationship between the size of the lateral brain ventricles on CT scan and either 'soft' signs or cognitive impairment. The findings do not provide evidence for an association between the presence of organic brain disorder (as indicated by the joint occurrence of neurological dysfunction and cognitive impairment) and either poor outcome or particular symptoms of schizophrenia. PMID- 4016438 TI - Behaviour and skills of severely retarded adults in hospitals and small residential homes. AB - The behaviour and self-help skills of mobile, severely or profoundly retarded adults with behaviour disorders, living in hospitals, were compared with those of a matched group in small homes outside hospital. The residents in the homes more often engaged in simple constructive activities. Although stereotypies were as common in the homes as the hospitals, in the former they were more likely to be combined with constructive pursuits. There were no differences between the groups in self-help skills. In the homes, the staff: resident ratios were higher and the staff had more autonomy in management and responsibility for organising their own services. The care practices in the homes were more resident-centred, and social contacts between staff and residents were more frequent. However, there was no evidence that, for this type of resident, placing a small home in a residential street had advantages over other geographical locations. PMID- 4016439 TI - The prevalence of chronic psychiatric morbidity: a community sample. AB - Several studies have commented upon the false negatives which can result when the General Health Questionnaire (GHQ) is employed as a community screening device for psychological distress. It would appear that some false negatives are the result of individual or cultural factors, whilst others result from the phrasing of the GHQ questions, which may mislead patients suffering from chronic disorders. This paper reports the use of additional questions, designed to detect such chronicity. PMID- 4016440 TI - Marital adjustment and treatment outcome in agoraphobia. AB - Forty agoraphobics had individual exposure treatment over a period of 28 weeks and were followed up for two years. Outcome in the 27 married patients was as favourable as that in the 13 single patients. However, among the married patients greater improvement occurred in those with better initial marital and sexual adjustment, although even those with poor initial marital adjustment improved significantly during treatment and maintained that improvement during follow-up. Good initial work adjustment and social adjustment were also predictive of particularly good outcome. Reduction of phobias was accompanied by stable or improved marital, sexual, social and work adjustment. PMID- 4016441 TI - Subcultural delusions and hallucinations. Comments on the Present State Examination in a multi-cultural context. AB - The challenges presented by the Present State Examination (PSE) in a multi cultural context are explored. The general approach to the use of this instrument, difficulties with rating items relevant to cultural or subcultural conditions, and particularly the assessment of psychosis are considered, as well as the possibility of additions to and modifications of the PSE-CATEGO system. Though disagreement exists as to whether the research model which the PSE represents is adequate to deal exhaustively with cultural factors, the instrument is useful in cross-cultural research and also in stimulating debate and crystallizing issues. PMID- 4016442 TI - Repetition of self-poisoning and subsequent death in adolescents who take overdoses. AB - Hospital Activity Analysis data and record linkage were used to investigate repetition of self-poisoning, and deaths, among 2,492 people, aged 12 to 20 years, who took overdoses between 1974 and 1978. Repetition occurred most frequently during the first few months after an initial admission; 9.5% of patients repeated within the study period (mean follow-up of 2.8 years). Ten of the 2,492 subjects died during the study period, and the average annual death rate in the cohort was approximately four times higher than the national average annual death rate in this age-group as a whole. Six of the deaths were probably suicides. Repetition and suicide rates were highest among males aged 16 to 20 years. PMID- 4016443 TI - Language in schizophrenia. The structure of monologues and conversations. AB - Experimental research into language in schizophrenia has been guided traditionally by two main assumptions: that language disturbance is widespread among schizophrenic patients and easy to detect and measure, and that schizophrenia is fundamentally a cognitive disorder in which language disturbance is part of an inability or failure to regulate one's thoughts. However, recent findings have challenged both assumptions. Two experiments are reported here, the first based on monologues, the second on conversations, which were subjected to reconstruction and discourse analyses. Schizophrenic material is found to be harder to follow than normal, and is characterised by poor reference networks and inappropriate use of questions. While some of the results are specific to the schizophrenic group, others are found also in affective patients, but none is the product of formal thought disorder. The central problem lies less in cognition than in the social process of taking the role of the other. PMID- 4016444 TI - Psychological profile of the spouse of the female agoraphobic patient. Personality and symptoms. AB - It has been contended that psychological characteristics of the partner of the agoraphobic patient are important factors in the development and maintenance of the patient's symptoms. To examine this hypothesis, male partners of female agoraphobics were compared with those of non-phobic psychiatric patients and of normal controls on a total of 48 measures referring to several symptom complexes and traits, including defensiveness. The partners of agoraphobics as a group were not found to be more defensive or psychologically more disturbed than their control counterparts. Additional within-couple analyses across groups showed spouses in the control couples to be more comparable to each other than were agoraphobics and their partners-a finding which was attributed to the highly elevated scores of the agoraphobic patients. PMID- 4016445 TI - Pairs of same-sexed siblings discordant for antisocial behaviour. AB - Seventy-one pairs of same-sexed biological adolescent siblings, discordant for antisocial behaviour and service contact, were compared using matched-pairs analyses along several dimensions which included developmental, family, psychiatric, educational, cognitive, pro- and antisocial behaviour. The antisocial youth had significantly more negative perception and experiences than their siblings, who experienced more protective influences. Earlier onset in the antisocial youth of activities such as smoking also significantly differentiated the pairs. The early temperament index alone correctly classified as proband and sibling 95% of the youth, using discriminant analysis procedures. The findings are relevant to the aetiology of antisocial behaviour and to possible treatment interventions. PMID- 4016446 TI - A comparative validation of the Foulds and Bedford hierarchy of psychiatric symptomatology. AB - This study investigated the validity of the Fould & Bedford hierarchical model of psychiatric illness, as compared to hierarchical models based upon prevalence and severity of disorder. The DSSI was administered to 52 American psychiatric in patients with severe disturbances. The reports of symptoms in this sample conformed to the Foulds hierarchy in 90% of cases, while 94% of cases conformed to a model based upon prevalence. When a cross-method validation was investigated, the Foulds & Bedford classification demonstrated good discriminative capacity, while models based upon prevalence and severity failed to achieve significance. These results suggest that the Foulds & Bedford model is a useful taxonomy of symptomatology in psychiatric illness. PMID- 4016447 TI - A mechanism to inhibit input activation and its dysfunction in schizophrenia. AB - Schizophrenics appear to be unable to regulate adequately the effects of external stimulation, but the cause of this deficit is unclear. Recent evidence suggests that input activation can normally be inhibited by an appropriate leading or conditioning stimulus; such inhibition has been found to be diminished in schizophrenics. Based on this evidence, a feed-forward regulating mechanism that serves to stabilise reactivity to environmental events is described; it is hypothesised that failure of the mechanism to inhibit adequately surges of activity is an underlying cause of schizophrenic symptoms. Some ways to test the validity of the mechanism are proposed, and an outline presented of steps to link the mechanism's dysfunction to schizophrenia. PMID- 4016448 TI - Neuroleptic serum levels measured by radioreceptor assay in patients receiving intramuscular depot neuroleptics. Some preliminary findings. AB - Twenty-six chronic schizophrenic patients on well established depot neuroleptic regimes with stable doses (16 on fluphenazine decanoate, ten on flupenthixol decanoate) had serum neuroleptic levels measured by a radioreceptor assay (RRA) method. The assay was sufficiently sensitive to measure serum levels in all cases, with acceptable levels of inter-assay variation. Blood level measurements were repeated on two occasions, at the same time interval from the last injection, in 18 patients (11 on fluphenazine decanoate, seven on flupenthixol decanoate) and remained reasonably stable in most cases, although others showed a wider variation. Despite a wide range of doses (X 32 fluphenazine decanoate, X 21 flupenthixol decanoate) the serum levels fell in a remarkably narrow range (X 4, X 6). There was a significant correlation between dose and blood level for flupenthixol decanoate, but not for fluphenazine decanoate. PMID- 4016449 TI - Neurotic patients who terminate their own treatment. AB - 40 new neurotic patients who lapsed from out-patient treatment were compared with 40 new neurotic patients who remained in treatment. The lapsed patients more often reported marital disharmony and 40% of them no longer felt ill at follow up. PMID- 4016450 TI - Maggot in the salt, the snake factor and the treatment of atypical psychosis in West African women. AB - We describe psychotic illness in a Nigerian and a Togoese woman respectively. Although the clinical presentation was familiar to the clinical team, neither responded to conventional methods of treatment. Detailed ethnic enquiry revealed cultural beliefs which had a profound impact on each illness. Swift recovery occurred after repatriation. Eisenbruch (1983) has reported a case of 'wind illness' in a paper described as a 'study of psychiatric anthropology', which stresses the importance of understanding the patient's own view of his illness and it causes, in arriving at the correct diagnosis and intervening effectively. We describe here two cases of atypical psychosis in West African women, which lead us to endorse this view; as in his case, Western medicine proved useless, although complete recovery occurred once both had been repatriated. PMID- 4016451 TI - British opiate addicts: an 11-year follow-up. AB - A cohort of 83 British addicts from one clinic was followed-up after 11 years; Home Office records and medical notes were personally searched to trace current status. Twenty-nine were still using drugs, 37 were not known to be using drugs, and 17 had died. The group still using drugs had become markedly more stable on parameters of drug use, criminality, and social stability over the follow-up period. PMID- 4016452 TI - Late paraphrenia. PMID- 4016453 TI - Dexamethasone suppression test. PMID- 4016454 TI - Suicide and parasuicide in childhood and early adolescence. PMID- 4016455 TI - Overdoses: explanations and attitudes in self-poisoners and significant others. AB - Marked differences were found between the reasons chosen to explain overdoses by the closest relatives or friends (the 'significant others') of 34 self-poisoners and those reasons chosen by the self-poisoners themselves. Whilst 41% of the latter claimed suicidal intent, in only one case was the significant other in agreement. The significant others were more likely to attribute manipulative reasons, commonly viewing the overdoses as directed at themselves, but the two groups agreed that the overdoses were often a means of alleviating distress. As well as evoking sympathy, the overdoses often caused the significant others to feel considerable guilt and anger. Discrepancies in the way self-poisoners and significant others interpret overdoses, and the strong feelings that overdoses evoke in the latter, should be considered during assessment and treatment of overdose patients. PMID- 4016456 TI - The risk of child abuse among mothers who attempt suicide. AB - The association between parental attempted suicide and child abuse was investigated in 114 mothers with children aged five years and under, referred to a general hospital following suicide attempts. The risk was greatly increased in the attempted suicide mothers, compared with both similar mothers at risk for depression and general population control mothers; well-documented risk of child abuse was identified in 29.8% of those who attempted suicide. No major differences were found between the attempted suicide mothers whose children were at risk and those whose children were not at risk. During the general hospital assessment of mothers with young children who attempt suicide, careful enquiry concerning the relationship with the children is essential. PMID- 4016457 TI - Mates of schizophrenic mothers. A study of assortative mating from the American Danish high risk project. AB - Both mates of schizophrenic mothers and a control group consisting of mates of non-schizophrenic mothers were diagnostically examined. The former were more frequently psychiatrically deviant than their controls, both with respect to a life-time syndrome diagnosis and a personality diagnosis. Mating between a schizophrenic mother and a father who suffered from schizophrenia spectrum disorder significantly increased the offspring's risk of developing a schizophrenia spectrum disorder himself. Assortative mating was negatively correlated with age of onset of maternal schizophrenia. It is proposed that defective emotional rapport or sub-psychotic features constitute the phenotypic traits by which assortative mating operates in schizophrenia. PMID- 4016458 TI - Plasma cortisol levels in mania: associated clinical ratings and changes during treatment with haloperidol. AB - Plasma cortisol levels were elevated in a large proportion of samples from manic patients. Although a correlation was found between clinical ratings of the severity of mania and the degree of elevation of daytime cortisol levels, some patients with low clinical ratings had elevated cortisol levels. During treatment with haloperidol, cortisol levels returned to normal earlier that the clinical state. The underlying mechanisms are discussed. PMID- 4016459 TI - Hereditary differentiation of anxiety and affective neuroses. AB - One hundred and fifty anxiety neurotic and neurotic depressive twin probands were differentiated into three groups by means of discriminant analysis, 50 in each group. The groups were named: pure anxiety neurosis, mixed anxiety-depression, and pure neurotic depression. Analysis of concordance rates indicated that only pure anxiety neurosis seemed to be influenced by hereditary factors. PMID- 4016460 TI - Speech pause time as a method for the evaluation of psychomotor retardation in depressive illness. AB - Psychomotor retardation is important in some depressed patients. We found that speech pause time (SPT) during a counting test correlated with the reaction time of both depressed patients and controls. It also correlated with global psychomotor retardation measured on Widlocher's scale. We demonstrated increased SPT in unipolar depressives, and also in retarded depressives as a group when compared with controls and with non-retarded depressives. SPT varied diurnally in controls, but not in depressed subjects. It did not correlate with biological markers of depression (REM sleep latency and the dexamethasone suppression test). It did, however, shorten during clinical improvement with antidepressant chemotherapy. PMID- 4016461 TI - Motor and sighting dominance in schizophrenia and affective disorder. Evidence for right-hand grip strength prominence in paranoid schizophrenia and bipolar illness. AB - Unusually frequent sinistral motor and sighting dominance have sometimes been reported in schizophrenics, although the majority of patients are still dextral. In this study, assessment of lateral dominance also included a measure of grip strength--a potentially more sensitive index of dominance or lateralised impairment; schizophrenics, non-schizophrenic patients (affective disorder), and normal controls were studied. There were no differences in handedness or sighting dominance. Affective patients, particularly bipolar psychotics, had greater right handed grip superiority than normals or non-paranoid schizophrenics. Paranoid schizophrenics were similar, being significantly greater in right-sided dominance than non-paranoids, who tended toward a smaller value than normals. Hand grip asymmetry was highly correlated with handedness in normals, but not in patients. The possibility is discussed that these results may reflect asymmetrical patterns of cerebral impairment or attentional bias. PMID- 4016462 TI - The medical and psychological investigation of psychogenic polydipsia: a case study. AB - The case of a 17 year-old female with psychogenic polydipsia is reported; 13 out of 18 members of her maternal family were known to have had polydipsia and polyuria, but only two had undergone endocrine investigations--one had diabetes insipidus and one also had psychogenic polydipsia. There are probable contributions of non-genetic family factors including imitation and identification to the development of this patient's condition. Detailed family and developmental histories may be of particular assistance in the understanding of the psychogenesis of the disorder in some patients. PMID- 4016463 TI - A 'pseudo-AIDS' syndrome following from fear of AIDS. PMID- 4016465 TI - Circadian rhythms. PMID- 4016464 TI - What price psychotherapy. PMID- 4016466 TI - The value of routine X-rays in dementia. PMID- 4016467 TI - De Clerambault's syndrome--a nosological entity. PMID- 4016468 TI - The psychiatric intensive care unit. PMID- 4016469 TI - The hive system. A model for a psychiatric service. PMID- 4016471 TI - An investigation of hysteria using the Illness Behaviour Questionnaire. AB - Seventy-nine patients with a diagnosis of hysteria were compared, on a number of variables, with a control group of neurological patients without psychiatric morbidity, and with psychiatric patients free from somatic complaints. Demographic information was obtained, and rating scales for the assessment of personality and mood, were administered, as well as Pilowsky's illness Behaviour Questionnaire. The data confirm the high incidence of affective disturbance in particular, depression and anxiety in patients with hysteria. There was no link between hysteria and early hospitalisation, although associations were found with sexual disturbances, a past history of vague or undiagnosed illness, affective inhibition, and denial. Relationships between personality and illness behaviour reveal links between personality dimensions and the reporting of illness. PMID- 4016472 TI - The emotional consequences of ejection, rescue and rehabilitation in Royal Air Force aircrew. AB - Retrospective questionnaire information was sought from in 175 Royal Air Force officers who had survived ejection from an aircraft and 88% replied. A profile of risk factors, both objective and subjective, was found in the 40% who subsequently experienced prolonged emotional disturbances. Confidential counselling of ejection survivors should therefore be routine. Consultation between involved medical staff and a Service psychiatrist can increase awareness that surviving aircrew may not be as composed and unaffected as they seem, while appropriate counselling can reduce prolonged emotional morbidity. PMID- 4016473 TI - Clinical judgements of self-dramatisation. A test of the sexist hypothesis. AB - It has been claimed that the diagnosis of histrionic personality disorder is inherently sexist. To estimate the extent to which psychiatrists are influenced by sexist prejudice in their judgements about self-dramatization (the central trait in the histrionic cluster), we conducted a study in which male and female subjects rated the degree of self-dramatization portrayed in videotaped vignettes. The results did not support the sexist hypothesis that dramatic behaviour would more often be attributed to a woman than to a man, especially by male raters. PMID- 4016470 TI - Stable abnormalities in the lateralisation of early cortical somatosensory evoked potentials in schizophrenic patients. AB - During the investigation of somatosensory evoked cortical potentials arising from a complex vibro-tactile stimulus to the forefingers, an abnormal lack of lateralisation of response was found in 10 out of 21 schizophrenic patients. Eight patients with severe affective illness all had the expected degree of lateralisation of cortical potentials, as did 12 out of 15 normals. Three normals and 3 schizophrenic patients had a loss of lateralisation of the evoked response on stimulation of one hand but a normal lateralisation on stimulation of the other. The considerable technical problems of this and related techniques are discussed, but it is suggested that further exploration of this technique is justified. At this stage, no conclusion can be drawn about the cause of the abnormalities. PMID- 4016474 TI - Law, psychiatry and women's imprisonment. A sociological view. AB - This paper analyses the legal and other social conditions under which the concept of 'psychopathic personality disorder' continues to play a strategic part in both the repeated imprisonment of female petty offenders and in the justifications put forward for the rigidity of the disciplinary regimes in women's prisons. PMID- 4016475 TI - Postnatal depression and child development. A three-year follow-up study. AB - This study investigates whether three-year-old children whose mothers had been depressed after their birth showed more behaviour disturbance than children of mothers who were not depressed at that time. Ninety-one of 103 mothers who took part in an earlier prospective study of postnatal depression were reinterviewed three years later to determine their present mental state, and to assess their child's behaviour, using Richman's Behavioural Screening Questionnaire. No relationship was found between a prolonged postnatal depression and behaviour disturbance in the child, but children whose mothers had brief postnatal depressive episodes showed more behaviour disturbance than those whose mothers had not been depressed since childbirth. PMID- 4016476 TI - Multiaxial classification of male sexual dysfunction. AB - Sexual dysfunction in male subjects is a multifaceted illness, not appropriately classifiable by any of the current diagnostic systems, in most of which a major disadvantage is their poor inter-rater reliability. This results in over-or underestimation of minor biological (e.g. hormonal) disturbances, which occur in conjunction with the disorder, but are unlikely to be only its pathophysiological correlate. These biological factors can be important in some cases, however, as they indicate therapeutic strategies (e.g. correction of a minor hormonal deficit). The broad acceptance of classificatory systems with multi-axial dimensions has prompted the construction of a new system. In accordance with DSM lll this consists of seven equivalent axes and sub-axes, supplemented by five sub types, from which the diagnostic attribution can be derived. PMID- 4016477 TI - Toward a biochemical classification of depressive disorders IX. DST results and platelet MAO activity. AB - Post-dexamethasone cortisol and platelet monoamine oxidase (MAO) activity levels were examined in 50 depressed patients. The incidence of non-suppression was significantly greater in patients with high platelet MAO activity than in those with low activity. Similar results were obtained when males and females were analysed separately. The mean 4 p.m. post-dexamethasone cortisol level was significantly higher in those patients who had high MAO activity than in their low MAO counterparts. Moreover, a statistically significant positive correlation was observed between platelet MAO activity and 4 p.m. post-dexamethasone cortisol levels. PMID- 4016478 TI - The relationship between scores on Ryle's Marital Patterns Test and independent ratings of marital quality. AB - This study concerns 250 marriages of 40-49 year-old women from a psychiatric patient and general population series. Psychiatric patients' marriages involved less exchange of affection, were husband-dominated, and were of poor quality. In general population marriages, poor quality was related to wife domination. Affection given (AG) and affection received (AR) scores were significantly associated, being high in good marriages and low in bad ones. Zero or near-zero domination was associated with high AG and AR scores and with good quality marriages. Husband domination was linked with wives having high (MMPI) dependency scores. Terminated marriages, compared with bad but non-terminated marriages, had significantly lower AR scores. PMID- 4016479 TI - Alcoholics. A twenty year follow-up study. AB - A 20 year follow-up on 133 alcoholics was carried out. Tracing methods are outlined and the difficulties reviewed. A questionnaire was completed by 40 subjects concerning drinking outcome, aids to recovery and morbidity. Mortality data are outlined and discussed for the 53 subjects who died during the follow-up period. PMID- 4016480 TI - The outcome of anorexia nervosa in younger subjects. AB - Twenty-one children who conformed to DSM-III criteria for anorexia nervosa, and who were aged 13 or younger at onset, were followed up after several years (mean = eight) using a range of outcome parameters. Comparison of these results with previous studies of later onset cases suggests that the age of onset of anorexia nervosa carries no prognostic significance. PMID- 4016481 TI - Erotomania in Schneider-positive schizophrenia. A case report. AB - A case of erotomania (de Clerambault's syndrome) in a female with Schneider positive schizophrenia is presented. The factors in her environment which may have precipitated the illness are discussed. The secondary nature of the syndrome is further illustrated by a discussion of the literature. In erotomania, the deluded victim, usually a woman, believes that a man, unattainable because of his social status, is in love with her. The nosological purity of the syndrome, despite its relative rarity, remains a subject of considerable debate. We present a case of erotomania in a female with schneiderian first rank symptoms (FRS) of schizophrenia (Schneider, 1959). PMID- 4016483 TI - Combined psychotherapy and pharmacotherapy for depression-the compliance variable. PMID- 4016482 TI - Vampirism--a clinical condition. PMID- 4016484 TI - The 'Stuck synapse' as a model for schizophrenia. PMID- 4016485 TI - Dysmorphophobia or monosymptomatic hypochondriasis? PMID- 4016486 TI - Early clinical experiences with sulpiride. PMID- 4016487 TI - The value of synovial biopsy. PMID- 4016488 TI - Pulmonary infiltrates and eosinophilia associated with naproxen. PMID- 4016489 TI - Felty's syndrome in an Asian. PMID- 4016490 TI - Methods of X-ray assessment in rheumatoid arthritis. PMID- 4016491 TI - Standardization and reliability of rheumatoid factor tests. PMID- 4016492 TI - Sex-typed labelling affects task performance. PMID- 4016493 TI - Experimental evaluation of various available contrast agents for use in the upper gastrointestinal tract in case of suspected leakage: effects on mediastinum. AB - The tissue reaction of seven contrast agents--pure barium sulphate, Micropaque, Hytrast, Dionosil, Gastrografin, Amipaque and Hexabrix-was evaluated on the mediastinum of rats. This work was undertaken to define the most suitable and safe contrast agent for use in the upper gastrointestinal tract in cases where leakage outside the gut into the mediastinum, pleura or peritoneal cavity may be suspected and aspiration may be an accompanying risk. Keeping in mind the danger of aspiration, Hexabrix and Amipaque appear to be the safest contrast media for the mediastinum. PMID- 4016494 TI - Abdominal lymphoscintigraphy: an effective substitute for lymphography? AB - Abdominal lymphoscintigraphy is a quick, easy, cheap and relatively non-invasive technique. In our study it appeared to be as accurate as lymphography, giving a positive correlation in 25 out of 32 patients (78%). In 11% of cases the lymphoscintigram detected an abnormality of lymph node function before macroscopic morphological change was seen in the lymphogram, indicating that in some instances lymphoscintigraphy is more sensitive than lymphography. The reason for this is unknown, although possible mechanisms are discussed and these are the subject of current further study. We believe this to be the first report of lymphoscintigraphy being more sensitive than lymphography for detecting lymph node disease. PMID- 4016495 TI - Measurement of lumbar spine bone mineral: a comparison of dual photon absorptiometry and computed tomography. AB - A comparison of computed tomography (CT) and dual photon absorptiometry (DPA) in the measurement of spinal bone mineral was made in 44 subjects of whom 26 had vertebral crush fractures. Although CT measures only trabecular bone within the vertebral body whilst DPA measures the whole vertebral segment, a good correlation was observed (r = 0.80) when these quantities were expressed in dimensionally similar units. Trabecular bone in the distal radius measured by CT correlated less well with vertebral CT (r = 0.65). Cortical bone in the radius correlated poorly with the spinal DPA measurement (r = 0.38). PMID- 4016496 TI - A comparison of the economics of xenon 127, xenon 133 and krypton 81m for routine ventilation imaging of the lungs. AB - We have compared the cost of providing routine lung ventilation scintigraphy using 127Xe with other radioactive gases in 100 patients. The physical properties of 127Xe permit a logical imaging sequence where a ventilation study is only carried out if indicated by perfusion scintigraphy which is performed first. With 133Xe, all patients must be ventilated prospectively, or a preselection carried out based on radiographic appearances at the time of imaging. This results in a greater number of ventilation studies than with 127Xe. Despite the greater cost per study of 127Xe, the overall cost of providing a routine diagnostic service with this gas is no more than that of using 133Xe in selected patients. The cost of ventilating all patients prospectively with 133Xe is considerably greater than using 127Xe only when indicated by abnormal perfusion images. If ventilation imaging is to be available at all times, either isotope of xenon costs very much less than 81Krm. We conclude that 127Xe is the radiopharmaceutical of choice for routine lung ventilation scintigraphy. PMID- 4016497 TI - The retention of metallic radionuclides in experimental abscesses in rats. AB - The retention of 67Ga, 203Hg, 175 + 181Hf, 239Pu and 241Am in turpentine-induced abscesses and in normal muscle has been studied in rats for periods of up to 126 days after radionuclide injection (129 days after turpentine). The results show that although the uptake of 203Hg is about 7 times greater in the abscess than in control muscle, the half time of the nuclide is similar in both tissues, T1/2 = 5 days. The remaining radionuclides studied all show a similar retention time in control muscle, average T1/2 = 12.5 days, and a more prolonged retention in the abscess tissue, average T1/2 = 47 days, although in both control and abscess tissue the uptake of the radionuclides showed quite large metal-specific variations. It is concluded that for radionuclides which are transported on transferrin in the blood and which deposit in lysosomes within cells a common metal clearance mechanism may operate in normal muscle and a second general mechanism may operate in abscess tissue. The radionuclide concentration difference between normal and abscess tissue ranged from 8 (67Ga) to 27 (239Pu); thus the radiation dose delivered to the inflamed tissue was between about 30 and 100 times greater than in normal muscle. PMID- 4016498 TI - The radiosensitivity of human neuroblastoma cells estimated from regrowth curves of multicellular tumour spheroids. AB - Multicellular tumour spheroids may provide a suitable in-vitro model for micrometastases in vivo. In this paper, the results are reported of experimental studies on the radiation response of two lines of spheroids derived from human neuroblastoma. Spheroids of approximately 200-250 microM mean diameter were exposed to graded doses of X rays (50-350 cGy) and, following a static or regression phase, regrew at rates which approximated those of unirradiated spheroids. Clonogenic surviving fraction was estimated, at each dose level, by extrapolation of the regrowth curve to zero dose. It is proposed that this procedure is more suitable for regrowth curves of spheroids than in-vivo tumours, because of the absence in vitro of complicating factors which occur only in vivo. By this means, survival curves were deduced and were found (for both cell lines) to be almost exponential in form, with little indication of capacity for accumulation of sublethal damage (multitarget parameters: DQ values: 17 and 25 cGy; Do values: 104 and 81 cGy respectively). These results contribute to the evidence for high radiosensitivity of neuroblastoma cells in vitro and provide a rationale for the use of hyperfractionation in the clinical treatment of neuroblastoma by radiotherapy. PMID- 4016499 TI - Tumour spread through the obturator foramen. PMID- 4016500 TI - Familial varices of the colon occurring without evidence of portal hypertension. PMID- 4016501 TI - Fine needle mediastinal cyst aspiration--a new therapeutic approach. PMID- 4016502 TI - Striated nephrogram in rhabdomyolysis. PMID- 4016503 TI - Rupture of a calcified renal cyst following blunt abdominal trauma. PMID- 4016504 TI - The tumour bed effect reflected in the radius of tumour cords. PMID- 4016505 TI - Method of cannula fixation for operative cholangiography. PMID- 4016506 TI - Management of gallstones in a district general hospital. AB - This survey reviews 815 consecutive patients undergoing surgery for benign biliary disease. There were no deaths following elective operations and the overall mortality was 0.7 per cent. One-third of patients had one or more complications. The mortality in patients having common bile duct exploration (n = 160) by one or more methods was 2.5 per cent (4 patients) with 46 per cent of these patients having complications. Of 95 patients undergoing duct exploration and postoperative T-tube cholangiography, 7 had unexpected residual calculi after initial cholecystectomy. Five have had further surgery to clear the duct. All patients having duct surgery alone for retained stones (n = 24) had previously had cholecystectomy with or without supraduodenal duct exploration. Of all patients undergoing choledochoduodenostomy or transduodenal sphincter exploration only one has returned with evidence of retained calculi. Patients with choledocholithiasis were examined in an attempt to identify a high risk group. These were found to be elderly patients, having emergency surgery for sepsis and on whom more than one duct procedure was performed (mortality 10 per cent). PMID- 4016507 TI - Sump syndrome following choledochoduodenostomy and its endoscopic treatment. AB - The clinical features of eight patients with 'sump syndrome' following side-to side choledochoduodenostomy are reported. The syndrome is defined and its aetiology discussed with special reference to debris in the common bile duct, bacterial overgrowth and the clinical picture of acute cholangitis, which does not appear to be necessary for the diagnosis to be made. Five patients were successfully treated by endoscopic sphincterotomy and a sixth by endoscopic removal of food debris from the sump. The other two patients had further surgery. PMID- 4016508 TI - Tuberculous pancreatic abscess. PMID- 4016509 TI - ERCP diagnosis of multiple hepatic abscesses due to portal pylephlebitis. PMID- 4016510 TI - Significance of positive bacterial cultures from aortic aneurysm contents. AB - Aneurysm contents were cultured in 275 patients out of a series of 546 cases undergoing infrarenal aortic aneurysm repair between 1961 and 1981. The incidence of positive cultures was 8 per cent. Cultures were more likely to be positive if taken from ruptured (16.7 per cent) and acute (9.1 per cent) aneurysms than from elective (4.2 per cent) cases (X2 = 6.69, P less than 0.01). Gram-positive organisms predominated with Micrococcus being the commonest isolate. Positive cultures were seen at an annual rate of 1-3 cases up to 1976 since which time all have been negative and we believe this may be due to prophylactic antibiotics being given preoperatively rather than postoperatively. The incidence of subsequent graft sepsis was greater in patients with positive aneurysm contents cultures (7 out of 22) than in those with negative cultures (6 out of 253) (X2 = 32.7, P less than 0.001). We recommend the routine culture of aneurysm contents to identify patients who are at high risk of developing graft sepsis and suggest that those cases with positive cultures receive prolonged organism-specific antibiotic therapy. In addition, there is evidence that pre-operative antibiotics may eliminate organisms from aneurysms, thus reducing the subsequent risk of graft sepsis. PMID- 4016511 TI - An aid to the biopsy of impalpable breast lesions. PMID- 4016512 TI - Strangulated omental hernia of the falciform ligament. PMID- 4016513 TI - Long-term survivors after breast cancer. AB - A retrospective analysis of two groups of patients, one surviving 16-20 years and the other dying within 10 years after diagnosis and treatment of primary breast cancer has been undertaken to determine whether there were particular clinical or histological features associated with long-term survival. The striking histological difference between the tumours of the two groups of patients was the prevalence of tumours of 'special' invasive types (cribriform, tubular, lobular and medullary) in the long-term survivors. Micro-invasive and non-invasive carcinomas were also more common in the survivors. The tumours of the surviving group which were not of a 'special' type more commonly had a better histological grade than those tumours of patients dying early from breast cancer. In the overall group elastosis was present in significantly more tumours of the survivors whereas tumour necrosis, vascular and lymphatic invasion were all significantly more common in the short-term survival group. Although there was a significantly increased incidence of earlier stage tumours in the long-term survivors, the histological distinctions between the two groups were independent of the differences in clinical features. PMID- 4016514 TI - Vasopressin effects on the small intestine: a possible factor in paralytic ileus? AB - Experiments were performed on luminally perfused, isolated, canine, jejunal segments in vivo to determine the effects of vasopressin on intestinal motility, myoelectrical activity and absorption. Intravenous vasopressin abolished spike activity and sometimes disrupted slow wave activity. The jejunum became atonic with intraluminal pooling of perfusate. Transit time was prolonged and intestinal absorption of water was decreased. Radionuclide imaging of the intestinal contents showed a doubling of intraluminal volume with vasopressin and confirmed the loss of intestinal motility. It is suggested that the high plasma levels of vasopressin which are known to follow laparotomy may be a factor in the development of postoperative ileus. PMID- 4016515 TI - Serum dependent variability in the adherence of tumour cells to surgical sutures. AB - Five commonly used surgical sutures were tested for their abilities to adhere tumour cells by an in vitro adherence assay. Adherence was quantified in vitro using radiolabelled tumour cells after standard incubation with a set length of the differing sutures. Tumour cells consistently adhered least to Prolene. All suture materials tested adhered significantly more tumour cells than Prolene (P less than 0.002 for chromic and less than 0.0001 for nylon, silk and Vicryl when compared with Prolene, with increasing cell numbers adhering to the sutures tested in that order). These differences in adherence were dependent upon an as yet unidentified macromolecule(s) in serum. All of the suture materials supported tumour growth in vivo after pre-incubation with tumour cells. Rapidity of in vivo tumour growth, however, correlated well with the in vitro tumour adherence characteristics of the different suture materials. The clinical significance of these findings is discussed. PMID- 4016516 TI - Restorative proctocolectomy with ileal reservoir for ulcerative colitis and familial adenomatous polyposis: a comparison of three reservoir designs. AB - One hundred and four patients were treated by restorative proctocolectomy with ileal reservoir for ulcerative colitis and familial polyposis. Three different designs of reservoir were used (triple loop 68, double loop 13, quadruple loop 23). There were no postoperative deaths but six (5.8 per cent) had the reservoir removed. Rates for pelvic sepsis were 25, 15 and 13 per cent, and for intestinal obstruction requiring laparotomy 14.7,0 and 8.6 per cent. Function was assessed in 88 patients (58, 12 and 18) after mean intervals from closure of the ileostomy of 23.7, 12.7 and 4.5 months. Frequency of defaecation per 24 h was 3.7 +/- 1.6, 5.5 +/- 1.6 and 4.1 +/- 1.3, being significantly greater for double loop reservoirs; night evacuation was more prevalent in the same group (26, 58 and 22 per cent). Significantly fewer patients with triple than with double loop reservoirs required antidiarrhoeal medication (19 and 58 per cent). Normal continence occurred in 67, 75 and 89 per cent of patients in the three groups. All patients with double or quadruple loop reservoirs defaecated spontaneously while only 41 per cent with triple loop reservoirs did so. Mean intra-operative reservoir volumes were 177 +/- 64, 172 +/- 58 and 325 +/- 37 ml and volumes after closure of the ileostomy were 416 +/- 176, 197 +/- 69 and 322 +/- 33 ml respectively. Double loop reservoirs were significantly smaller than the other two designs after ileostomy closure. There was an inverse relationship between reservoir volumes and frequency. A quadruple loop reservoir directly connected to the anal sphincter preserved spontaneous evacuation and resulted in function similar to that obtained with the triple loop reservoir. PMID- 4016517 TI - Experience of posterior division of the puborectalis muscle in the management of chronic constipation. AB - Nine women with severe chronic constipation who were unable to expel a water filled rectal balloon underwent posterior division of the puborectalis muscle. Pre-operative concentric needle electromyography and measurement of the anorectal angle at rest and during straining suggested that the puborectalis muscle failed to relax during attempted defaecation in these patients. Two patients reported improvement after surgery and had normal balloon expulsion after operation. However seven patients reported no benefit from surgery and tests of defaecatory function and anorectal angle did not change. Incontinence for solid stool was not reported following puborectalis muscle division although five patients reported incontinence of flatus, liquid stool and mucus. PMID- 4016518 TI - Inguinal herniotomy in children: a five year survey. AB - This retrospective review covers our experience over 5 years of 436 hernia repairs in 392 children upto the age of 15 years. The number of emergency presentations was 71 (18.1 per cent) and 66.2 per cent of these were under the age of 12 months. Most cases were initially treated conservatively and only 18 children required operation on the day of admission. There were 11 recurrences (7 elective and 4 emergency cases) giving a recurrence rate of 2.5 per cent. In all eleven cases the original operation was performed by a junior surgeon. The complication rate (excluding recurrences) was 2.8 per cent but may be an underestimate because of the limitations of a retrospective study. We suspect our results are typical of those to be found in any large British hospital and that with careful training and supervision of junior staff in the technique of inguinal herniotomy the results could be improved and approach those found in specialist paediatric units in America. PMID- 4016520 TI - Treatment of rectal prolapse by sphincteric support using silastic rods. AB - The use of silastic perianal rings to control rectal prolapse in the elderly has been reviewed. Forty-one patients were treated over a 6 year period by a total of 52 operations. Their mean age was 80 years and there was no operative mortality. Prolapse was adequately controlled in 71 per cent of patients, and a further three patients had no recurrence despite failure and removal of the ring. The results of this procedure are inferior to those obtained by abdominal operations for rectal prolapse, but deserve serious consideration in those elderly patients who may be unfit for laparotomy. PMID- 4016519 TI - Prolonged bandaging is not required following sclerotherapy of varicose veins. AB - Following sclerotherapy of varicose veins, 158 limbs of 154 patients were randomized to be bandaged with either crepe or Coban for 6 weeks each, or with Coban for 3 days only. Objective assessment of vein eradication and subjective evaluation of symptoms 3 months after completion of treatment showed no clear differences between these regimens. Significantly more discomfort was experienced with Coban than crepe when used for 6 weeks. It is suggested that, following sclerotherapy, 3 days is an adequate period of bandaging when using Coban. Such a policy would considerably reduce the inconvenience to patients during treatment. PMID- 4016521 TI - Small bowel tumours causing intussusception in childhood. AB - In a series of 292 children with intussusception ten (3.5 per cent) were caused by small bowel tumours. The average age of these patients was greater than in idiopathic cases; seven of the ten being older than 2 years. Intussusception due to Peutz-Jeghers hamartomas was jejunojejunal whereas other small bowel tumours causing intussusception were in the terminal ileum. The majority of these intussusceptions were either irreducible or gangrenous and all required resection of bowel. There was only one death in the entire series of 292 patients, and this was a child with lymphosarcoma. PMID- 4016522 TI - Postoperative pain and pulmonary complications: comparison of three analgesic regimens. AB - In a prospective study, patients undergoing cholecystectomy were randomly allocated to receive (a) intermittent intramuscular morphine (n = 25), (b) continuous intravenous morphine infusion (n = 25) or (c) epidural bupivacaine (n = 25) for postoperative pain relief. Morphine by intravenous infusion provided comparable pain relief to intermittent intramuscular morphine; there was no significant difference in the incidence of postoperative pulmonary complications. Patients receiving epidural bupivacaine for 12 h had better analgesia than patients receiving morphine (P less than 0.001). Arterial oxygen tensions were also significantly higher in the epidural group for the first three postoperative days (P less than 0.05). Epidural analgesia was associated with a significant reduction in the incidence of pulmonary complications (P less than 0.01) and chest infection (P less than 0.05). PMID- 4016523 TI - Cannibalization of a Gore-tex aortohepatic graft by the duodenum. PMID- 4016524 TI - The incidence of abdominal aortic aneurysm. PMID- 4016525 TI - Typhoid enteric perforation. PMID- 4016526 TI - Frequency of pulmonary embolism. PMID- 4016527 TI - Computer-based records. PMID- 4016528 TI - The continuing conundrum of testicular torsion. PMID- 4016529 TI - Internal hernia following T tube drainage. PMID- 4016530 TI - Prospective study of the Angelchik anti-reflux prosthesis. AB - Fifty patients with medically refractory gastro-oesophageal reflux were treated by the insertion of an Angelchik anti-reflux prosthesis. All patients had a pre operative upper gastrointestinal endoscopy, 32 were investigated with 15 h overnight oesophageal pH studies combined with oesophageal bile sampling and 20 underwent oesophageal manometric studies. At pre-operative endoscopy 45 patients had evidence of oesophagitis and the 5 who did not had pathological reflux demonstrated on overnight pH testing. Postoperatively the main clinical problem was dysphagia which appeared to settle with time but left one-third of patients with mild dysphagia at the end of 12 months. A further 12 per cent had residual moderate to severe dysphagia which required the removal of the prosthesis in five patients (10 per cent). In only one patient was the dysphagia due to prosthetic migration and this was the first patient in the series. Subsequently, we have had no problems with prosthetic migration, disruption, or erosion into the oesophagus. The overnight pH studies confirmed the efficacy of the prosthesis in preventing reflux which correlated with symptomatic improvement. We conclude that, while the Angelchik anti-reflux prosthesis is an effective device, it has a disturbingly high incidence of postoperative dysphagia though this appears to settle with time, leaving around 10 per cent of patients with severe dysphagia which will necessitate removal of the prosthesis and one-third with mild dysphagia which may settle with the further passage of time. PMID- 4016531 TI - The Angelchik anti-reflux prosthesis--some reservations. AB - A prospective study has been made of the use of the Angelchik prosthesis in the treatment of hiatus hernia and gastro-oesophageal reflux. Forty-one patients under the care of one surgeon were studied over a 3-year period. The operation is simple and safe to perform. Twelve patients suffered transient dysphagia which spontaneously resolved within 3 months. Satisfactory results were obtained thereafter in 80.9 per cent. Seven of the prostheses have been removed (17.1 per cent), all within 18 months of performing the operation. Dysphagia and recurrent symptoms were the main reasons for removal and in two of these stricturing was present pre-operatively. We feel the presence of an established stricture is a contraindication to the use of the device. We have, however, been impressed by its use as a second procedure when previous surgery has failed and when revisional surgery for recurrent hiatus hernia is difficult due to dense adhesion formation. While it is still early to assess the legacy that the use of this prosthesis might incur, we would recommend conservatism if not abandonment of its use until longer-term evaluation is available. PMID- 4016532 TI - Growth rate of abdominal aortic aneurysms as measured by computed tomography. AB - The risk of rupture of an abdominal aortic aneurysm increases with size. It has thus been recommended that small aneurysms be continuously followed with some type of imaging technique to detect when aneurysm size constitutes an indication for surgery. The present study focuses on the growth rate of abdominal aortic aneurysms in 35 patients who were subjected to repeated computerized tomographic examinations of their abdominal aortic aneurysms. Several aneurysms were measured more than twice resulting in 57 different examinations. The mean growth rate of the transverse diameter was 0.52 cm/year. The individual growth rates were, however, variable. Aneurysms with an initial transverse diameter exceeding 6 cm showed a slightly but not significantly faster increase in size compared with smaller aneurysms. No correlation between initial size and growth rate could be established. Six patients died during the study period, two from myocardial infarction, three after elective aneurysm operations and one, refused for elective operation, died after rupture. It is concluded that the growth rate measured with computed tomography agrees well with previously reported estimates obtained with ultrasonography. It is recommended that small aneurysms particularly in patients with relative contraindications to surgery be followed with repeated examinations of size. PMID- 4016533 TI - Cystic adventitial disease of the common femoral artery communicating with the hip joint. PMID- 4016534 TI - Spontaneous simultaneous internal and external biliary fistulae. PMID- 4016535 TI - Artefactual breast disease: a report of three cases. AB - Three cases of suspected artefactual conditions of the breast are presented, one case each of recurrent bleeding, recurrent infection and atypical eczema. Involvement of the breast is rare, but may go undiagnosed in many cases. Patients are usually married and in the second half of their reproductive life. An unusual pattern of disease appearance and behavior, lack of response to treatment, inappropriate affect and a request for mastectomy are helpful in suggesting the diagnosis. A disturbance in personal relationships can often be elucidated by psychiatric assessment. Treatment is difficult and may be limited to suspecting the diagnosis, excluding organic disease and avoiding unnecessary and repetitive surgery. PMID- 4016536 TI - Complications and hospital stay after surgery for breast cancer: a prospective study of 385 patients. AB - General complications, wound complications and hospital stay after surgery for operable mammary carcinoma were studied prospectively in 385 patients treated by either modified radical mastectomy (324 operations) or segmental resection with axillary dissection (71 operations). The overall infection rate was 3.6 per cent. Postoperative seromas were noted in 34.8 per cent of the wounds. Other complications were few. The average hospital stay was 7.2 days. Seventeen per cent of the total number of days in hospital for these patients were due to factors other than the mammary cancer. PMID- 4016537 TI - Carcinoid tumours of the appendix. AB - Appendicular carcinoid tumours in 147 patients are presented. Two patients had evidence of metastatic spread at the time of presentation. Both patients had primary tumours less than 2 cm in diameter. Size remains the most reliable guide to the malignant potential of these tumours. If, after simple appendicectomy, a carcinoid tumour is found with a post-formalin fixation diameter greater than 1.5 cm then a subsequent right hemicolectomy should be considered. PMID- 4016538 TI - Surgery for acute ulcerative colitis and toxic megacolon during pregnancy. PMID- 4016539 TI - The biliary tract in patients with acute gallstone pancreatitis. AB - The biliary tract has been prospectively studied in a consecutive series of 769 patients undergoing surgery for gallstones to determine whether differences exist between subjects with and without a history of acute pancreatitis. The incidence of acute gallstone pancreatitis (AGP) was 7.7 per cent and men with gallstones were significantly more likely to develop pancreatic inflammation. Operations on patients with AGP were accompanied by a higher mortality rate which was almost entirely due to the severity of the disease at the time of surgery. The earlier operations were performed after the onset of pancreatitis the more often stones were found in the common bile duct and at the ampulla. Patients with AGP had smaller and more numerous gallbladder stones in association with a wider cystic duct that controls. The common bile duct diameter in patients with AGP was independent of the presence of choledochal calculi implying either previous temporary obstruction to the biliary tree or a dilated duct ab initio. Pancreatic duct reflux was far more commonly observed on the cholangiograms of patients with AGP and in these patients reflux occurred into a wider pancreatic duct, at a greater angle and was associated with a longer functioning common channel. No patient developed recurrent pancreatitis following biliary surgery. These features strongly support the concept of gallstone migration and suggest that patients with gallstones who develop acute pancreatitis have essential differences in their biliary tree which mechanically facilitate migration of calculi. PMID- 4016540 TI - Chemical composition of biliary calculi in relation to the pattern of biliary disease in Singapore. AB - The chemical composition of biliary calculi from 25 Singapore patients operated upon over a three month period was determined by a microanalytical technique and equilibrium swelling tests. Twelve patients had biliary calculi confined to the gallbladder and the main component of six calculi was cholesterol. In the other 6 patients, the dark brown to black pigment calculi contained bilirubin and calcium and a small quantity of cholesterol, but the chief component was an insoluble pigment with the swelling characteristics of a bilirubin polymer. These cholesterol and pigment calculi have similarities in composition to gallstones of Western patients. In 13 patients with cholangitis, the brown, soft pigment calculi found in the dilated bile ducts (and also concurrently in the gallbladder in 5 patients) had bilirubin as the main component. Fatty acid was frequently present. The insoluble pigment component was considerably less but the lower swelling ratio suggested more cross linkage compared with black gallbladder stones. Differences in chemical composition between pigment gallbladder and bile duct calculi support the concept that Western type cholelithiasis and Oriental cholangitis occur as separate disease entities in Singapore patients. PMID- 4016541 TI - Malignant lymphoma as a complication of ureterosigmoidostomy. PMID- 4016542 TI - Radial forearm flap for floor of mouth reconstruction. AB - Approaches to reconstructing floor of mouth defects are reviewed including methods of bony reconstruction following mandibular resection. The place of the free radial forearm flap, incorporating vascularized hemiradius if necessary, is described together with the anatomy, operative technique and a review of seven cases. It is concluded that this flap is an important addition to current methods of reconstructing substantial intraoral soft tissue defects alone or associated mandibular defects as well, owing to the high quality of results and to its low morbidity. PMID- 4016543 TI - Metronidazole and Augmentin in the prevention of sepsis after appendicectomy. AB - Two hundred and fifty patients were admitted to a prospective randomized trial to compare the efficacy of Augmentin with metronidazole in the prevention of sepsis after appendicectomy. Pre-operatively they received either 500 mg metronidazole or 1.2g Augmentin intravenously. Those patients with gangrenous or perforated appendices received eight additional doses of the trial drug at 8 hourly intervals. Overall there were 13 wound infections in the Augmentin group (11 per cent) and 21 in the metronidazole group (18 per cent). The 90 per cent confidence limits for the overall 7 per cent difference in infection rates were +/- 8.5 per cent. There were high rates of wound infection in the gangrenous group (Augmentin 8 per cent versus metronidazole 19 per cent) and especially in the perforated group (Augmentin 33 per cent versus metronidazole 63 per cent). There was no statistically significant difference between the infection rates with the two antibiotics but our study suggests that Augmentin, which is active against both aerobes and anaerobes, may be more effective than metronidazole in reducing wound sepsis after appendicectomy. PMID- 4016544 TI - Demonstration of a reduction in postoperative body protein breakdown using the Clinitron fluidized bed with an ambient temperature of 32 degrees C. AB - Patients managed at an elevated ambient temperature after major surgery have a less pronounced rise in postoperative urinary nitrogen excretion. To investigate the mechanism involved, body protein breakdown was assessed, using a tracer dose of labelled amino acid, in patients following aorto-bifemoral bypass surgery nursed on either a Clinitron fluidized bed at 32 degrees C or a hospital bed at 22 degrees C and correlated with urinary total nitrogen excretion. Results showed a small reduction in measured body protein breakdown on the second postoperative day in patients managed on the Clinitron fluidized bed at 32 degrees C (2.92 +/- 0.91 versus 3.23 +/- 0.84 g protein kg-1 day-1; mean +/- s.d.), which was equivalent to the mean protein sparing (0.29g protein kg-1 day-1) demonstrated by the significant improvement in urinary total nitrogen excretion (9.20 +/- 2.0 versus 12.48 +/- 3.9 g N day-1; mean +/- s.d.: P less than 0.05). Urinary total nitrogen excretion (N) and body protein breakdown (B) showed a weak though significant positive correlation (B = 1.25 + 13.13N; r = +0.55: P = 0.05), whereas no correlation existed between urinary total nitrogen excretion and the derived rate of body protein synthesis. There was also a significant decrease in postoperative stress, measured during the isotope infusion, in patients managed on the Clinitron fluidized bed at 32 degrees C (12.3 +/- 2.2 versus 16.1 +/- 3.2 per cent activity incorporated into plasma proteins; mean +/- s.d.: P less than 0.05). These results show the beneficial effect of managing postoperative patients on a Clinitron fluidized bed at 32 degrees C in conserving body nitrogen through a reduction in body protein breakdown, probably as a consequence of decreased postoperative stress. PMID- 4016545 TI - Heparin with and without graded compression stockings in the prevention of thromboembolic complications of major abdominal surgery: a randomized trial. AB - One hundred and seventy-six patients scheduled for elective major abdominal surgery were randomized to two prophylactic regimens to prevent postoperative thromboembolism. All patients were screened with the 125I-labelled fibrinogen uptake test, and thromboembolism was verified by ascending phlebography and/or perfusion/ventilation lung scintigraphy. In the group of patients receiving low dose heparin treatment (5000 units twice daily subcutaneously) 12 per cent developed thromboembolic complications. In the other group, where low-dose heparin treatment was supplemented with graded compression stockings only 2 per cent developed thromboembolism. It is concluded that the combination of low-dose heparin and the use of graded compression stockings is superior to heparin alone in preventing thromboembolism following major abdominal surgery. PMID- 4016546 TI - Zinc deficiency and the prolonged accumulation of zinc in wounds. AB - Zinc is required for protein synthesis and therefore for wound healing. Zinc levels were 50 per cent higher in muscle and skin from abdominal wounds of rats during the maturation phase of wound healing, but mild deficiency greatly reduced this accumulation. The results suggest that zinc takes part in the late stages of wound healing when protein is laid down, and that such extra local demands expose otherwise marginal zinc deficiency. PMID- 4016547 TI - Cholecystokinin (CCK) cholecystography and biliary pain. PMID- 4016548 TI - Infection following biliary surgery. PMID- 4016549 TI - Signs of retroperitoneal haemorrhage: visible pulsation of the anus. PMID- 4016551 TI - [Chromosome polymorphism]. PMID- 4016550 TI - [The male 46,XY karyotype in a female phenotype]. PMID- 4016552 TI - [Genetic aspects of febrile convulsions]. PMID- 4016553 TI - [Chromosome anomalies in spontaneously aborted fetuses and a study of mutagenesis in a human population]. PMID- 4016554 TI - [Cytogenetics of hemoblastoses]. PMID- 4016555 TI - [Chromosome analysis in cases of perinatal death]. PMID- 4016556 TI - [Incidence of chromosome anomalies in 123 married couples with reproductive loss]. PMID- 4016557 TI - [Various aspects of prenatal and perinatal reproductive loss]. PMID- 4016558 TI - [Comparison of therapeutic approaches in subacute thyroiditis]. PMID- 4016559 TI - [The role of clinical genetics units in the development of a central registry of genetic diseases]. PMID- 4016560 TI - [Complications of peridural anesthesia. Study of 218 peridural anesthesias for peripheral vascular surgery]. PMID- 4016561 TI - [Peridural anesthesia and surgery of the spine]. PMID- 4016562 TI - [Dorsal anesthesia of the penis. Complementary analgesia for circumcision]. PMID- 4016563 TI - [Intravenous loco-regional anesthesia in surgery of the upper extremity in the child]. PMID- 4016564 TI - [Cardiotoxicity of recent local anesthetics. Consequences for anesthetic technic]. PMID- 4016565 TI - [Inhalation of gastric contents and cardiac arrest during peridural anesthesia]. PMID- 4016566 TI - [Is total arthroplasty of the hip justified in cirrhotics?]. PMID- 4016567 TI - [Fatal accident related to the condition of anesthetic equipment]. PMID- 4016568 TI - [Prolonged survival after cardiac fissure treated medically]. PMID- 4016569 TI - [Value of anesthetic consultation in an ENT service]. PMID- 4016570 TI - [Fatal poisoning with cyproheptadine]. PMID- 4016571 TI - Studies on the uptake of fatty acids by brush border membranes of the rabbit intestine. AB - Initial studies revealed that the uptake of palmitic acid and oleic acid into brush border membranes was similar when these were isolated from either whole small intestine, jejunum, or ileum. The uptake of these fatty acids was somewhat lower with membranes obtained from duodenum. Subsequent studies, all with membranes obtained from whole intestine, indicated an increase in binding with chain length of fatty acid of up to 16 carbons. Unsaturation decreased this uptake somewhat. Taurocholate and 1-palmitoyl lysolecithin had a moderate stimulatory effect on the binding of oleic acid and palmitic acid at concentrations of 10 and 0.5 mM, respectively, and inhibited at higher concentrations. Addition of 1.4 mM egg lecithin to the fatty acid - bile salt micelles, such that the lecithin - bile salt ratio was 0.2, decreased the uptake of fatty acids generally, but did not significantly affect the pattern of binding by membrane fractions isolated from different segments nor did it change the pattern of labelling when fatty acid chain length and unsaturation were varied. At lower concentrations, egg lecithin had little effect on the uptake of oleic acid, whereas dipalmitoyl phosphatidylcholine stimulated binding of both palmitic acid and oleic acid over the entire range of concentrations tested. Preincubation of the membranes with this saturated phospholipid stimulated the uptake of oleic acid, and addition of this choline lipid to the oleic acid - bile salt containing micelles did not substantially enhance fatty acid uptake in lipid-treated membranes. The binding of fatty acid was very rapid either in the presence or the absence of Ca2+, such that even in zero-time controls essentially equilibrium bindings were obtained.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4016572 TI - Cone-shaped lipids increase the susceptibility of phospholipids in bilayers to the action of phospholipases. AB - Addition of cardiolipin or diacylglycerol to dispersions of phosphatidylcholine greatly increased hydrolysis by snake venom or pancreatic phospholipase A2, as well as by a microbial phospholipase. Monogalactosyl diglyceride which, like cardiolipin and diacylglycerol, will form nonbilayer hexagonal II structures also caused an increase in the breakdown of phosphatidylcholine. Addition of digalactosyl diglyceride, a bilayer lipid from the same source, had a much smaller effect on the three phospholipases, indicating that stimulation by the nonbilayer lipids was not due to their fatty acid compositions. Stimulation of the microbial phospholipase by cardiolipin did not require the presence of calcium, leading to the conclusion that the formation of nonbilayer structures was not necessary. The results suggest that cone-shaped lipids increase the accessibility of lipids in bilayers to phospholipases by decreasing the packing of the polar head groups. PMID- 4016573 TI - Assignment of lectins specific for D-galactose or N-acetyl-D-galactosamine to two groups, based on their circular dichroism. AB - The circular dichroism (CD) spectra of thirteen lectins, most being specific for D-galactose or N-acetyl-D-galactosamine, were compared. Two groupings are proposed on the basis of the CD in the near-ultraviolet region. Group one comprises the lectins from Arachis hypogaea, Glycine max, Phaseolus coccineus, P. lunatus, P. vulgaris, and Vicia villosa, and group two comprises lectins from Caragana arborescens, Cytisus sessilifolius, Dolichos biflorus, Griffonia simplicifolia, and Wisteria floribunda. The CD spectra of lectins from Bauhinia purpurea and Sophora japonica were different from any of the other lectins. CD difference spectra produced by the two sugars were distinctive for each protein, suggesting that the combining sites of these lectins are not homologous despite similarities in specificity and that the CD spectral similarities arise from residues in other, more homologous regions of the proteins. PMID- 4016574 TI - Involvement of phospholipids in the modulation of a membrane-bound brain fucosyltransferase. AB - Microsomal fucosyltransferase isolated from sheep brain is strongly enhanced by charged lysophospholipids such as lysophosphatidylinositol and lysophosphatidic acid, while the corresponding phospholipids are inhibitive. Lysophosphatidylcholine (lyso-PC) also greatly increases the enzymatic activity and leads to its solubilization. Its stimulatory effect is related to the length of the fatty acyl chain involved in the lyso-PC structure: fatty acids C18 and C20 are less activating than the fatty acids C14-C16. Stimulation is restored when C18 fatty acids are unsaturated (e.g., C18:1-C18:3). Enzymatic activity enhancement is decreased when phosphatidylcholine structures are reformed by the addition of lyso-PC and the corresponding fatty acid. The physical state of these structures has no influence. These data provide evidence that bilayer structures do not modify enzymatic activity, while micellar structures formed by detergents and lysophospholipids lead to a strong increase in fucosyltransferase activity. However, lyso-PC does not interact in exactly the same way as Triton X-100. Although they both enhance the maximal velocity of fucosyltransferase for its two substrates, GDP-fucose and asialofetuin, the effect with lyso-PC is greater, and it clearly enables a better affinity for GDP-fucose. Endogenous phospholipids are also able to modify enzymatic activity. Hydrolysis of phosphatidylcholine by phospholipase A2 leads to an enzymatic stimulation. PMID- 4016575 TI - Purification and preliminary characterization of 2-monoacylglycerol acyltransferase from rat intestinal villus cells. AB - We have purified the monoacylglycerol acyltransferase from rat small intestinal mucosa to homogeneity by a combination of hydrophobic absorption, guanidine dissociation, and gel filtration. The purified enzyme gives a single band of 37 000 daltons on sodium dodecyl sulphate--polyacrylamide gel electrophoresis. The enzyme has a specific activity of about 5900 nmol/mg per hour and represents 0.12% of total cell protein, corresponding to about a 600-fold purification. The enzyme does not acylate diacylglycerols to triacylglycerols, which is consistent with the separate physical existence of the mono- and di-acylglycerol acyltransferases. The enzyme acylates the 2-monoacylglycerols to yield an essentially racemic mixture of diacylglycerols. It does not acylate glycerol-3 phosphate. PMID- 4016576 TI - Association of fodrin with brain microtubules. AB - We have compared the polypeptide composition of microtubules isolated from bovine brain by the conventional in vitro reassembly method with those obtained by direct isolation of brain microtubules into a stabilizing buffer. The stabilizing buffer included 6.7 M glycerol to limit the rate of subunit exchange between assembled and unassembled states. The microtubule-associated proteins normally found by in vitro reassembly are also found in the stabilized preparation, but in smaller proportions. Fodrin, a brain membrane-associated protein believed to be homologous to spectrin, was found to be the most abundant component after tubulin in the stabilized microtubules. The ratio of tubulin to fodrin, 16:1 by mass, was almost constant at each stage of the preparation. Some actin was initially present in the stabilized microtubules, but was gradually lost during purification. When stabilized microtubules were diluted into cold aqueous buffer, they depolymerized and the recovered microtubule protein could then be purified by in vitro reassembly. The composition after this treatment resembled that of microtubules prepared initially by reassembly in vitro. The missing fodrin was found to be removed in the preliminary centrifugation and was unavailable for incorporation into growing microtubules during the in vitro assembly step. This suggests that the standard in vitro reassembly procedure for purification of microtubules may distort the composition of microtubule-associated proteins. PMID- 4016577 TI - Antibiotic susceptibilities of Salmonella species isolated at a large animal veterinary medical center: a three year study. AB - The antibiograms of 408 Salmonella species isolated from large animals were collected during a three year study from 1981 through 1983. The predominant Salmonella serogroup among these isolates was group B. A consistently high percentage of all isolates were resistant to ampicillin and tetracycline. A pattern of increasing resistance to chloramphenicol and gentamicin was documented for serogroup B isolates while the susceptibility of the isolates to neomycin increased. There was a decrease in the incidence of susceptibility to sulfamethoxazole-trimethoprim among the group E isolates. These changes were not as remarkable, nor as alarming, as the overall decreased susceptibility to chloramphenicol and gentamicin. An evaluation of the principles concerning use of antimicrobial agents in veterinary medicine for treatment of Salmonella infections is recommended. PMID- 4016578 TI - Microorganisms associated with pneumonia in slaughter weight swine. AB - The lungs of 334 pigs were obtained from two slaughter plants in Minnesota and examined in detail. Macroscopic and microscopic evaluation, direct fluorescence for Mycoplasma hyopneumoniae and bacterial culture were done on all of them and a subsample of 50 were selected for virus culture. Mycoplasma hyopneumoniae, Pasteurella multocida and Haemophilus spp. were detected in 24.0%, 34.1% and 27.0% of the lungs, commonly in conjunction with each other. One isolate of Haemophilus pleuropneumoniae serotype 2 was detected and this represents the first report of its presence in the United States. No virus was detected in any of the lungs. Lungs with both M. hyopneumoniae and Pasteurella multocida had the greatest amount of macroscopic pneumonia (9.8% of the lung). Lungs with M. hyopneumoniae or P. multocida alone had 4.9% and 5.2% of the lung involved with pneumonia respectively. Lungs with Haemophilus sp. Taxon "minor group" had 3.8% of the lung involved which was not significantly different from lungs with none of these organisms being detected (1.6%). There was a positive correlation between the extent of M. hyopneumoniae infection, as scored by FAT and the amount of macroscopic pneumonia present (r = 0.46; P less than 0.001). Likewise, there was a positive correlation between the estimated concentration of P. multocida present, as scored by the relative number of colonies on blood agar and the amount of macroscopic pneumonia present (r = 0.60; P less than 0.001). Microscopically, the amount of lymphoreticular proliferation, polymorphonuclear cells and alveolar macrophages were evaluated.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4016579 TI - Clinical and antibody responses to Clostridium perfringens type A enterotoxin in experimental sheep and calves. AB - Clostridium perfringens type A live cultures or sonicated sporulating cells, all containing enterotoxin, were repeatedly inoculated into sheep and calves by the intraduodenal route over periods of 30 to 35 days. Serum antibody to C. perfringens enterotoxin, tested by ELISA, developed in four of seven sheep and in two of four calves. The titers ranged from 400 to 1600. The live organism introduced into the duodenum did not become established in the bacterial flora of the intestinal tract. PMID- 4016580 TI - Comparison of tissue reactions produced by Haemophilus pleuropneumoniae vaccines made with six different adjuvants in swine. AB - Tissue damage caused by six different adjuvants incorporated in a Haemophilus pleuropneumoniae vaccine was compared in swine. The adjuvants compared were four mineral oil compounds, one peanut oil compound and aluminum hydroxide. Inoculations were given in the neck, quadriceps and semitendinosus muscles. The mineral oil adjuvants were highly irritant and caused extensive areas of granulomatous inflammation that were present at eight weeks after injection. The aluminum hydroxide produced smaller lesions that also persisted for eight weeks. Only the peanut oil adjuvant did not produce significant lesions at the site of injection. At two and four weeks, but not at eight weeks postinoculation, lesions in the quadriceps and semitendinosus muscles were approximately twice as extensive as those in the muscles of the neck. PMID- 4016581 TI - Immunoglobulin transfer and weight gains in suckled beef calves force-fed stored colostrum. AB - Concentrations of immunoglobulins and total proteins in second-day post-partum serum samples of 62 beef calves from multiparous dams were measured by zinc sulphate turbidity, electrophoresis, radial immunodiffusion and refractometry. These results, together with health records and weight gains, were used to evaluate the practice of routinely force-feeding 1 L of stored colostrum to suckled beef calves immediately after birth. There was no apparent benefit from such force-feeding. It did not result in greater 48-hour serum immunoglobulin levels, nor did it improve weight gains at 42 days. None of the calves required treatment for neonatal disease, but one force-fed calf died from inhalation of regurgitated colostrum. PMID- 4016582 TI - The effect of cow's dietary copper intake, sire breed, age on her copper status and that of her fetus in the first ninety days of gestation. AB - The liver copper concentration of the bovine fetus and the hepatic and plasma copper concentrations of its dam during the first trimester of pregnancy were studied. The effect of the dam's dietary copper intake, age, sire breed and stage of pregnancy on her copper status and that of her fetus was also investigated. Simmental sired heifers had the lowest plasma copper concentration. The younger cows (two, three and four years) had significantly lower liver copper concentration than the older cows (six and seven years). The bovine fetal liver copper concentration was approximately 3.1 mmol/g DM and was not affected by dam's age, breed, stage of pregnancy, or copper status. PMID- 4016583 TI - Trace element levels in liver and kidney from cattle, swine and poultry slaughtered in Canada. AB - Levels of arsenic, cadmium, copper, mercury and lead were determined in approximately 650 samples of liver and kidney from cattle, swine and poultry slaughtered in Canada during 1979-81. In addition zinc levels were determined in livers and kidneys from swine, and selenium and zinc levels were determined in the livers and kidneys from cattle. Depending on the element several methods of atomic absorption spectroscopy were used to analyze samples including flame, hydride generation, cold vapour generation and graphite furnace atomization. Analyses were also done by plasma emission spectroscopy. Levels of arsenic over 2.0 micrograms/g were detected in 0.9% of swine livers and 0.3% of swine kidneys. Cadmium levels higher than 1.0 micrograms/g were detected in 0.3% of cattle livers, 10.8% of cattle kidneys, 1.8% of swine kidneys, 0.4% of poultry livers and 0.3% of poultry kidneys. Levels of copper over 150 micrograms/g were detected in 0.4% of cattle and swine livers. Levels of lead over 2.0 micrograms/g were detected in 1.4% of poultry livers and 1.6% of poultry kidneys. The highest level of mercury detected in all species was 0.25 micrograms/g and the highest level of selenium was 1.9 micrograms/g. Zinc levels of over 100 micrograms/g were detected in 1.7% of cattle livers, 0.2% of cattle kidneys and 5.0% of swine livers. PMID- 4016584 TI - Premedication of dogs with acepromazine or pentazocine before euthanasia with carbon monoxide. AB - Euthanasia of unwanted or sick animals should always be done in a humane manner. This study involving two groups of 12 dogs evaluated a two step method of euthanasia using first acepromazine or pentazocine then inhalation of carbon monoxide. During the experiment, behavioral reactions (anxiety, agitation, vocalization and sphincter relaxation) and physiological parameters (electro encephalogram, electrocardiogram, arterial blood pressure, respiratory and heart rates and serum cortisol) were monitored. The results showed that both drugs modified many behavioral reactions and physiological changes associated with administration of carbon monoxide. Acepromazine and pentazocine reduced by 25% and 20% respectively the number of dogs that showed vocalization and agitation. In acepromazine premedicated dogs, the duration of these signs was significantly diminished and sphincter relaxation did not occur in more than 50% of cases. Furthermore, with the use of acepromazine, no significant peaks or drastic drops were noticed in the heart and respiratory rates and in the arterial blood pressure. These manifestations are usually related to stress. In light of these results, it is recommended to premedicate dogs with acepromazine before submitting them to euthanasia by carbon monoxide inhalation. PMID- 4016585 TI - Cranioschisis aperta with encephaloschisis in cephalothoracopagus hamster twins. AB - The results of gross and histopathological study of a near-term male hamster exencephalic lateral cephalothoracopagus are presented. There was minimal duplication of the internal organs to the point of division at the abdomen. The appendicular skeleton was relatively unaffected by the severe malformations of the axial skeleton. The studies suggested that the lateral relationship of the skull to the spinal columns was a consequence of the presence of two embryonic neural tubes; the chordomesodermal systems of the right and left twins apparently contributed the tissues for the right and left cephalic neural folds, respectively. Anomalies of the vertebral bodies and neural arches were not related to failure of closure of the neural tube as there was no evidence for rachischisis in either body half. Rather, the anomalous axial skeletal elements were apparently the result of competing fields of development by two chordomesodermal systems. The twins were recovered from a dam maintained on a diet consisting of 80% cassava, a cyanide-containing staple consumed by humans in tropical countries. Because the numbers of resorbed implantation sites and malformed litermates were low and the failure to produce conjoined twins in other litters recovered from dams given cassava diets, it appears unlikely that the malformation was related to the composition of the diet. PMID- 4016586 TI - Social stress and resistance of chicken and swine to Staphylococcus aureus challenge infections. AB - The purpose of this research was to determine the effect of social stress on the susceptibility of chickens and swine to Staphylococcus aureus infection. Chickens were housed under four levels of social stress. Weaned pigs remained with their litter or were housed separately. One day after some birds were placed in the high stressed environments all were challenged intravenously with S. aureus. Susceptibility was characterized by joint infection in swine and reduced weight gain in chickens. Chickens which were moved into the high stressed environments before challenge lost weight while the controls gained weight (P less than 0.001). During the three days postchallenge the most severely stressed chickens lost less than half as much body weight as did the least stressed (P less than 0.001). During the post-challenge period chickens selected for high corticosterone response in a high social stress gained weight while chickens selected for a low corticosterone response in a low stress environment lost weight (P less than 0.0001). Swine housed under a reduced level of stress (social) were more susceptible to S. aureus than those kept under higher levels of stress (P = 0.0001). PMID- 4016587 TI - Effects of aerosolized histamine and carbachol in the conscious horse. AB - Pulmonary function tests were performed in seven conscious, standing horses. Changes in pulmonary mechanics and ventilation volumes were measured after inhalation challenge with saline (baseline), histamine (1% w/v solution for 5 min) and carbachol (0.5% w/v solution for 3 min). Comparisons between baseline and posthistamine values revealed a significant (P less than 0.05) increase in nonelastic work of breathing (Wb), maximum change in transpulmonary pressure (max delta Ppl), and pulmonary resistance (RL), while dynamic compliance (Cdyn) decreased (P less than 0.05). Tripelennamine completely abolished these histamine induced changes suggesting the involvement of H1 receptors. A nonsignificant increase occurred in functional residual capacity. However, the amount of nitrogen retained in the lung at the end of a nitrogen washout test was significantly (P less than 0.05) greater after histamine when compared to baseline values. The effect of carbachol was qualitatively similar to that of histamine, Wb and max delta Ppl increased while Cdyn decreased (P less than 0.05). The increase in lower RL reached statistical significance (P less than 0.05) only at the beginning of expiration (/ 25% VT). The present investigation demonstrates that the physiological measurements of lung function could be carried out in conscious, unsedated horses and that the pulmonary function test methods could be used as a tool for study of drug induced changes in pulmonary mechanics. PMID- 4016588 TI - Pasteurella multocida infection in the domestic rabbit: immunization with a streptomycin-dependent mutant. AB - Fourteen Pasteurella multocida-free rabbits were inoculated intranasally with a streptomycin-dependent mutant of P. multocida serotype 12:A. Vaccinations with approximately 10(8) colony forming units were done on days 0, 14 and 28. Two weeks later the animals were separated into groups, which included 12 rabbits divided into two control groups of six unvaccinated Pasteurella-free animals. Seven vaccinated rabbits were challenged intranasally with the homologous virulent parent strain and the other seven vaccinates were challenged with a virulent strain of serotype 3:A. Rabbits were necropsied two weeks later. The vaccinated group challenged with the parent strain showed a more rapid nasal clearance of the organism than the vaccinated group challenged with the heterologous strain. However, the number of positive cultures of P. multocida recovered from tissues post-challenge were similar in vaccinated and control animals. In a significant number of animals, vaccination with serotype 12:A induced detectable antibody production to somatic antigens of both 12:A and heterologous strain 3:A. PMID- 4016589 TI - Natural and experimental respiratory infections of calves. PMID- 4016590 TI - Longitudinal evoked potential studies in hereditary ataxias. AB - We studied multimodal evoked potentials (EPs) longitudinally in a series of children with Friedreich's ataxia and ataxia telangiectasia to determine both their diagnostic utility and their correlation with clinical regression. The auditory brainstem responses (ABRs) were abnormal only in the children with Friedreich's ataxia. The abnormality seen in these patients was a rostral-caudal loss of the ABR waves. The visual EPs (VEPs) were abnormal in many of the patients; those with ataxia telangiectasia had unusually low amplitude or absent VEPs, occasionally with increased latencies, whereas those with Friedreich's ataxia had normal amplitude VEPs, often at increased latencies. The somatosensory EPs were usually of increased latency or absent in these patients. Unlike the ABR and VEPs, they did not serve to differentiate the groups. Changes in the EPs appeared to reflect clinical deterioration; patients with little change in their EPs over several years were regressing very slowly, whereas others had rapid deterioration in both EPs and clinical status. We suggest that the EPs are diagnostically of value in degenerative ataxias and may be of value in monitoring these patients and their response to therapy. PMID- 4016591 TI - [Does the brain influence the muscular development of the human fetus? Evidence in 21 cases]. AB - The importance of suprasegmental cerebral influence on developing human fetal muscle is less well understood than the control of histochemical differentiation of muscle by the motor neuron. Muscle biopsies of 21 hypotonic infants and children with nonprogressive congenital lesions of the cerebellum and/or brainstem were studied by histochemical methods. Two neonates who died with severely dysplastic brains and no descending motor tracts had normal muscle. The others, particularly those with cerebellar hypoplasia, had delayed muscle maturation, selective predominance of type I or II muscle fibres or disproportion in fibre sizes. It is concluded that the motor unit is capable of developing normally without suprasegmental influence, but that an abnormal balance of descending impulses may alter histochemical differentiation of fetal muscle. The small 'subcorticospinal' pathways arising in the brainstem probably are more influential than the larger corticospinal tract because of later myelination in the latter. The muscle biopsy thus serves to provide evidence of suprasegmental disease in infantile hypotonia. PMID- 4016592 TI - Pitfalls of incomplete myelography with thoracic spinal lesions. AB - This paper describes four patients with thoracic spinal lesions in whom the initial clinical presentation was highlighted by complaints in the lower back and lower extremities, in the absence of thoracic spinal or radicular symptoms. Initial myelography, confined to the lumbar region, failed to reveal a cause for the patients' symptoms. Subsequently, diagnostic consideration of a thoracic spinal lesion prompted repeat myelography of the thoracic region which demonstrated a relevant lesion in each case. It is important to visualize the thoracic cord when myelography is performed for the investigation of pain or neurological symptoms in the lower back or lower extremities. PMID- 4016593 TI - Pupillary abnormalities in congenital neurosyphilis. AB - Pupils in congenital neurosyphilis differ from the classic Argyll-Robertson pupil in acquired cases, and often tend to be large and unreactive. Constriction to pilocarpine in the reported patient would suggest that peripheral parasympathetic damage is responsible for such pupillary findings. Congenital neurosyphilis should be included among the causes of "tonic" pupil. PMID- 4016594 TI - The association of extracranial and intracranial vascular malformations in children. AB - This review is an attempt to relate the types of angiomas and other cutaneous vascular lesions appearing in the face with abnormalities in the formation of cerebral vessels including arteries at their origin, veins and venous sinuses, and with other less constant alterations that affect other organs, particularly the heart and cerebellum. After angiographic study of a series of patients exhibiting diverse types of vascular nevi (capillary and cavernous hemangiomas, nevus flammeus, and lymphangiomas), a correlation was established for each type of dermal nevus with a corresponding group of intracranial vascular anomalies. An explanation of these malformations based on the embryological development of the principal cerebral vessels during the 7th and 8th weeks of gestation is offered. Involvement of the facial and scalp dermatome innervated by the first sensory trigeminal branch correlates most consistently with the presence of abnormal cerebral vessels. The capillary hemangioma occurs preferentially in girls and frequently is associated with developmental anomalies of major cerebral arteries characterised by the absence of some adult vessels and the persistence of others that should have disappeared during embryogenesis such as the fetal trigeminal artery. The complete angiographic exploration of the cerebral vessels from their origin in the aortic arch to the phase of intracranial venous evacuation may reveal unexpected important findings, and is recommended for children with major facial vascular nevi, even if they are neurologically asymptomatic. PMID- 4016595 TI - The effects of local cooling on canine spinal cord blood flow. AB - The internal spinal cord blood flow was measured in dogs at the site of local cooling using hydrogen polarography. Blood flow decreased to 50% of the normothermic values during cooling of the cord to a central temperature of 16 degrees Celsius. Upon cessation of cooling internal blood flow rapidly returned to normal values. Implications of this finding for the treatment of spinal cord injury are discussed. PMID- 4016596 TI - Binswanger's disease: progressive subcortical encephalopathy or multi-infarct dementia? AB - Since Binswanger's description of subcortical arteriosclerotic encephalopathy in 1894, numerous cases have been reported. Several authors doubt the validity of this malady, although the majority consider it to be a disease entity. We report seven cases with this type of pallor of myelin, only two of which are accompanied by a history of dementia. Among the seven cases, two had arteriosclerosis of penetrating arteries and arterioles in cerebral white matter. Electron microscopy showed splitting of myelin sheaths, probably the result of edema. In reviewing the blood supply of the cerebral white matter, we conclude that no pathological alterations of medullary branches of the cerebral arteries, the same vessels supplying the white matter, can give rise to such diffuse pallor of white matter and spare the arcuate fibres. This pallor can only be due to cerebral edema, most likely of hypoxic-ischemic, hypotensive, or acidotic origin. We also contend that arteriosclerosis can only cause dementia through multiple infarcts or lacunae, if it indeed leads to dementia. PMID- 4016597 TI - Efficacy of phenobarbital in neonatal seizures. AB - A retrospective study of neonatal seizures in a tertiary care neonatal intensive care unit determined a 3.2% incidence, and confirmed the relatively poor efficacy of the traditional anticonvulsants phenobarbital and phenytoin. Only 33% responded to an initial adequate loading dose of phenobarbital, while 56% responded to either or both anticonvulsants. Although multifocal clonic seizures were most common (42%), tonic seizures were next in frequency (30%). Tonic seizures which did not respond to phenobarbital responded quite poorly to the addition of phenytoin compared to other seizures types. Tonic seizures may be the result of brainstem release phenomena and require a different strategy for management. Among nonresponders in this study, there was a 56% mortality rate but only 33% of responders died. There is a critical need for studies to find more efficacious agents than phenobarbital and phenytoin to treat seizures in the newborn. PMID- 4016598 TI - Occult breast cancer and changing patterns of surgical practice. PMID- 4016599 TI - Morbidity audit, Canadian Society for Vascular Surgery. PMID- 4016600 TI - Occult breast cancer. PMID- 4016601 TI - Mediastinal packing for refractory bleeding after open-heart surgery. PMID- 4016602 TI - Choledochoduodenal fistula and gallstone ileus in the absence of the gallbladder. PMID- 4016603 TI - Ethics in research on surgical techniques: a conversation. PMID- 4016604 TI - Cancer of the colon and rectum: 30-year follow-up study. AB - This study reviews the course of all patients registered at the Saskatoon Cancer Clinic between 1949 and 1951, with histologically proven cancer of the colon or rectum. The data were abstracted, coded and analysed by life-table methods. Follow-up was complete to death or to 1982. There were 403 patients (58.3% were men). Cancer of the rectum accounted for 51% of the total, the sigmoid colon 22% and the cecum 10%. The primary tumour was resected by abdominoperineal resection, hemicolectomy or segmental colectomy in 63% of the patients; colostomy alone was performed in 21%. The overall survival was 31% at 5 years, 24% at 10 years, 15% at 20 years and 7% at 30 years from diagnosis. Many of the deaths in this relatively elderly group of patients were due to causes other than the cancer. Considering cancer-related causes of death only in patients with resectable lesions, the cumulative probability of survival at 5, 10, 20 and 30 years was 63% +/- 4%, 54% +/- 4%, 48% +/- 4% and 47% +/- 6%, respectively (probability +/- 1 standard error), for those without lymphadenopathy, and 14% +/- 3%, 12% +/- 2%, 10% +/- 2% and 9% +/- 3%, respectively, for those with involved nodes. Death from the cancer was rare after 10 years while deaths from competing causes continued to occur, at a near constant rate, for 30 years. The data suggest that the cancer was eradicated in one third of all patients, and in one half of patients in subgroups with no lymphadenopathy or with shallow primary lesions. PMID- 4016605 TI - Changing patterns in the management of locally advanced breast cancer: a preliminary report. AB - Over the 8 years from 1976 to 1983, 28 patients with stage IIIB (T4a,b,c, NX-2, M0) and inflammatory breast cancers without evidence of disseminated disease at the time of diagnosis were treated at Ellis Fischel State Cancer Center in Columbia, Mo. This group comprised 4% of all cases of primary breast cancer seen during that period. Radiotherapy was the primary treatment in one half of the group during the first 4 years of the study (group A). Since 1981, locally advanced breast cancer has been treated by multidrug chemotherapy followed primarily by mastectomy (group B). The rate of local control was the same for both groups (78%). However, the median survival for group A was 11 months, only one patient being alive 5 years after diagnosis, whereas in group B, 12 of 14 patients were alive and clinically free of disease 9 to 31 months after diagnosis with a median follow-up of 16.5 months. This preliminary report confirms recent findings, supporting the use of polychemotherapy followed by mastectomy in the management of patients with locally advanced breast cancer. PMID- 4016606 TI - Intraoperative localization of occult breast tumours. AB - Mammographic examination of the clinically normal breast can identify some breast masses before they become palpable. In order to remove them successfully, a surgeon requires the help of some localization procedure. The only method recommended to date has been preoperative needle localization under radiologic control by a radiologist. A technique of intraoperative needle localization by the surgeon without radiologic control has been developed at St. Michael's Hospital, Toronto. The method saves time, avoids complications and is very accurate. Because of the possibility that the mass is malignant, the excisional biopsy is performed as a definitive lumpectomy. Of 112 consecutive occult tumours so localized, only 3 required removal at a second operation. Twenty-six (23%) of the lesions proved to be cancer (16% invasive, 7% noninvasive). PMID- 4016607 TI - Transforming skeletal muscle for myocardial assist: a feasibility study. AB - Canine experiments were undertaken to determine the feasibility of transforming skeletal muscle for myocardial assistance. Initially, a rectus-muscle pedicle flap was used to power a ventricular assist conduit. A specially designed "pulse train" stimulator produced skeletal muscle contractions capable of augmenting myocardial function. Statistically significant increases in either systolic or diastolic pressures were achieved by appropriate synchronization and signal delays of the stimulator. Then, the left rectus muscle was conditioned by stimulating it at low frequencies (2 to 10 Hz) for 6 to 12 weeks. The degree of transformation from type II (fast) to type I (slow) fibres was examined and the resultant tolerance to fatigue studied. Preliminary data show that a greater proportion of type I fibres is associated with increased resistance to fatigue. Such transformed skeletal muscle should therefore be more suited to power the cardiac assist devices. PMID- 4016608 TI - Two-dimensional echocardiography for diagnosing acute ascending aortic dissection. AB - The diagnosis of type A aortic dissection (involving the ascending aorta) can be made with two-dimensional echocardiography, but surgeons usually demand angiographic confirmation. Between January 1983 and February 1984, 10 patients presented at St. Michael's Hospital in Toronto with type A aortic dissection. Six patients underwent two-dimensional echocardiography early in their evaluation. A positive diagnosis was made in four, based upon visualization of an intimal flap or a false lumen. In the other two patients, the findings of an enlarged ascending aorta and pericardial effusion were suggestive but not diagnostic. Three patients survived operation and are alive and well (follow-up ranging from 3 to 5 months). One patient died while awaiting surgery, one died during aortography and one died during operation. All echocardiographic and angiographic findings were confirmed at surgery or at autopsy. It is concluded that two dimensional echocardiography can diagnose ascending aortic dissection quickly, accurately, easily and without risk to the patient. In selected cases the presence of a false lumen or of an intimal flap makes it possible to proceed with operation without delay or the potential hazards of aortography. PMID- 4016609 TI - Organization of the department of surgery to facilitate undergraduate education. AB - The chairman of the department of surgery is responsible for undergraduate education and should develop an organizational structure involving a director of undergraduate education for the every-day running of the undergraduate program and the determination of policies. This person should hold a relatively senior position and should have undergone specialist postgraduate training in educational methods and theory. The director should be supported by appropriate secretarial services and be compensated for this; the director should also sit on the faculty medical curriculum committee to close the circle of policy made at this committee with departmental policy. The departmental undergraduate education committee should include representatives from all hospitals involved in undergraduate education with representatives from the various systems. Some doubling up of representatives can occur. There should be a review process of both teaching methods and faculty teaching. The former will encourage change where appropriate and the latter award individuals for their contribution to the teaching process. PMID- 4016610 TI - Evaluation of surgical faculty and surgical undergraduate teaching. AB - Surgical teachers are interested in being evaluated. In a survey of 89 such teachers at the University of Manitoba, most (79%) preferred having their undergraduate teaching evaluated by their students to other methods of evaluation. Eighty-seven percent of North American departments of surgery had a mechanism for assessing the quality of undergraduate teaching; 97% used student feedback. In order for the evaluation to be effective in improving undergraduate teaching, there must be serious faculty commitment, the teachers must know the criteria for evaluation, and feedback to the teachers should be early and preferably coupled with teacher self-assessment. This paper lists criteria for the evaluation of surgical undergraduate teachers and outlines the evaluation instrument currently used in the Department of Surgery at the University of Manitoba. PMID- 4016611 TI - The role of the department of surgery in undergraduate education. Development of the undergraduate teacher. AB - Three components are necessary for effective undergraduate teaching in a department of surgery: (a) departmental organization and membership priority focused on teaching; (b) a clear understanding and appropriate utilization of all teaching methods, for example, lectures, large seminars or demonstrations, small seminars and bedside teaching; (c) the acquisition and maintenance of teaching and evaluation skills by all department members. The author discusses the advantages and disadvantages of the four principal teaching methods and the means of acquiring teaching and evaluation skills that includes the use of professional educators. PMID- 4016612 TI - Fatal, overwhelming sepsis after splenectomy in the community hospital. AB - Charts of all patients who underwent splenectomy between 1965 and 1981 at the Orillia Soldiers' Memorial Hospital were reviewed. At the end of 1983, the patient, relatives or family physician were contacted for follow-up. Eighty spleens were removed, 36 for medical reasons, 30 for trauma and 14 because of iatrogenic injury. Of the patients followed up, 51 were alive and 13 had died. Three died in the postoperative period and seven died of unrelated causes. Three patients died of overwhelming sepsis, 1, 3 and 7 years after splenectomy. If the three postoperative deaths are excluded and it is assumed none of the 16 untraced patients died of overwhelming sepsis, the incidence of death from this cause was 3.9%. PMID- 4016613 TI - Management of pancreatic trauma. AB - Between 1974 and 1984, 25 patients with pancreatic trauma were seen at three Regina hospitals. Eighteen had blunt injuries and 7 penetrating injuries. The mean injury severity score was 37 and the mean age 24.5 years. Management was nonoperative in six patients. Of the 19 treated surgically, 14 underwent laparotomy and drainage, 2 laparotomy without drainage and 3 pancreatic resection. Complications related to pancreatic injury occurred in 11 patients. One patient died. The results of this series suggest that the majority of patients with pancreatic injuries can be treated by laparotomy and drainage with a low mortality, but the complication rate is high. In select patients, visualization of the pancreatic duct may allow the surgeon to perform definitive surgical management at the initial procedure. PMID- 4016614 TI - Etiology of choledochal cysts: two instructive cases. AB - The etiology of choledochal cysts is controversial. The authors report two cases which show that type 1 cysts (axial dilatation of the common bile duct and common hepatic duct) may be caused by a biliary web and that some choledochoceles (type 3 cyst) may actually be duodenal duplications (i.e., having an outer wall of smooth muscle lined with gastrointestinal mucosa and being adherent to the gut). PMID- 4016615 TI - Numeracy--what is it, and who needs it? PMID- 4016616 TI - Medical profession sending smoky signal? PMID- 4016617 TI - Acid neutralization capacity of Canadian antacid formulations. PMID- 4016618 TI - Got it all. PMID- 4016619 TI - Is there a future for homeopathy? PMID- 4016620 TI - Diuretic-induced hypokalemia in hypertension. PMID- 4016621 TI - The fate of "outstanding postdischarge data". PMID- 4016622 TI - Management of human bite injuries of the hand. AB - On the basis of experience at the Ottawa Civic Hospital over the past 10 years, a classification of and protocol for the management of human bite injuries of the hand are presented. Early exploration of such wounds under local anesthesia improves the outcome by facilitating adequate cleansing of the wound and enabling deep structures to be visualized. In this way the risk of major sepsis and of the disability so frequently associated with these innocent-looking injuries can be reduced. PMID- 4016623 TI - Etiology of shock in blunt trauma. AB - Patients who have suffered blunt trauma and present in shock of uncertain cause represent a problem frequently encountered by emergency physicians. A retrospective review of the charts of 879 patients who had suffered blunt trauma and presented to a regional trauma unit over a 44-month period revealed that 154 of the patients had presented to either a hospital or the trauma unit in shock. The most common causes of shock when a single source of hemorrhage was identified were, in order of decreasing frequency, intraperitoneal hemorrhage, pelvic or other musculoskeletal fractures, thoracic hemorrhage, severe head injury and spinal cord injury. Severe head injuries accounted for only 8% of the single source cases and contributed to shock in only seven of the remaining cases. PMID- 4016624 TI - Review of traumatic injuries in regional federal penitentiaries. AB - The incidence of major injuries in inmates of Canadian prisons has steadily increased in recent years. The medical records of the emergency department serving virtually all prisoners at federal penitentiaries in the Kingston, Ont. area were reviewed for cases of traumatic injury. In the 30-month period ending Mar. 1, 1984 there were 353 visits to the emergency department, of which 140 were for accidental injuries and 213 for injuries resulting from violence. Of the injuries caused by violence 75 (35%) were self-inflicted and 138 (65%) were inflicted by others. Of the 75 inmates with self-inflicted injuries 17 required admission to hospital, and 12 of these underwent surgery. Of the 138 inmates injured by others 50 were admitted to hospital, and 6 of these were transferred to the neurosurgical or cardiothoracic department at Kingston General Hospital; 31 of the 50 underwent surgery, and 4 died in hospital as a result of their injuries. PMID- 4016625 TI - Nomifensine-induced dyskinesia. PMID- 4016626 TI - Gastric volvulus within the foramen of Morgagni. PMID- 4016627 TI - Delayed diagnosis in atypical measles syndrome. PMID- 4016628 TI - Visualization of Toxoplasma gondii in the cerebrospinal fluid of a child with a malignant astrocytoma. PMID- 4016629 TI - Effect of the immunization program in Ontario schools. PMID- 4016630 TI - OMA's computerized billing system benefitting physicians. PMID- 4016631 TI - The need for a new specialty: medical informatics. PMID- 4016632 TI - More on the grooves of academe. PMID- 4016633 TI - Variations in cesarean section rates. PMID- 4016634 TI - Extrahepatic tuberculous pseudotumour. PMID- 4016635 TI - The World Health Organization and cancer. PMID- 4016636 TI - The involuntary house husband: recipe for disaster? PMID- 4016637 TI - Reuse of permanent cardiac pacemakers. AB - Cardiac pacemakers are part of a growing group of expensive implantable electronic devices; hospitals in which 100 pacemakers are implanted per year must budget over $300 000 for these devices. This cost represents a considerable burden to health care resources. Since the "life-span" of modern pacemakers often exceeds that of the patients who receive them, the recovery and reuse of these devices seems logical. Pacemakers can be resterilized and tested with current hospital procedures. Reuse should be acceptable under Canadian law, but the manner in which the pacemakers are recovered and the patients selected should follow careful guidelines. Every patient should provide written informed consent before receiving a recovered pacemaker. Properly executed, reuse of pacemakers should provide a high level of health care while maintaining or reducing the cost of these devices. PMID- 4016638 TI - Limited usefulness of lymphocytopenia in screening for AIDS in hospital patients. AB - Lymphocytopenia is often present in patients with acquired immune deficiency syndrome (AIDS) and has been suggested as a useful screening test for AIDS. Of 625 patients consecutively admitted to an acute care university teaching hospital 91 (15%) were found to have a lymphocyte count of less than 1 X 10(9)/L, and 25 (4%) had a count of less than 0.5 X 10(9)/L. The corresponding figures for 32 patients at the hospital in whom AIDS had been diagnosed were 13 (41%) and 4 (13%). Absolute lymphocyte counts in hospitalized patients should not be used as the sole means of identifying patients at high risk for AIDS. PMID- 4016639 TI - Lactobezoar in a low-birth-weight neonate. PMID- 4016640 TI - Reye's syndrome in British Columbia. PMID- 4016641 TI - Suboptimal response to hepatitis B vaccine in Nova Scotia. PMID- 4016642 TI - Aeronautics Act changes medical practice. PMID- 4016643 TI - Spectre of commercialism dominates transplant symposium. PMID- 4016644 TI - Abortion. PMID- 4016645 TI - The nuclear threat and Canadian children. PMID- 4016646 TI - Trends in the prevalence of alcohol and other drug use among Ontario students: 1977-1983. PMID- 4016647 TI - The relationship between sex education and knowledge in grade eight students. PMID- 4016648 TI - Adolescent health needs: perspectives of health professionals. PMID- 4016649 TI - Noise induced hearing loss and leisure activities of young people: a pilot study. PMID- 4016650 TI - A comparison of the school performance, emotional adjustment and skill development of poor and middle-class children. PMID- 4016651 TI - Comparison of mail questionnaire and telephone interview as data gathering strategies in a survey of attitudes toward restrictions on cigarette smoking. PMID- 4016652 TI - Effect of a program of aerobic exercise on the smoking behaviour of a group of adult volunteers. PMID- 4016653 TI - Performance of mentally retarded adults on the Canadian Standardized Test of Fitness. PMID- 4016654 TI - Growth instability of French-Canadian children during the first three years of life. PMID- 4016655 TI - Lower respiratory disease in Indian and non-Indian infants. PMID- 4016656 TI - A waterborne epidemic of acute infectious non-bacterial gastroenteritis in Alberta, Canada. PMID- 4016657 TI - Relationship between higher prevalence of smoking and weight concern amongst adolescent girls. PMID- 4016658 TI - Who uses natural family planning? PMID- 4016659 TI - Children of parental divorce: vulnerable or invulnerable? PMID- 4016660 TI - Parent's perceived responsibility for children's problems. AB - Beliefs about parents' influence on their children's behaviour have developed over the last 300 years. During this century multiple socio-economic, ideological and technological changes have combined to leave expert and lay person alike in a sea of confusion and ambiguity about optimal parent-child relationships. While fashions in child rearing change, the mother is usually accorded responsibility for the child's behaviour and social skills. In this study parents attending a multidisciplinary pediatric clinic were asked their opinion of the source of their child's emotional or behavioural problem. Describing confusion and conflicting advice, most parents had concluded that the problem had multiple roots. Between male and female parents, however, a marked difference was evident in the attribution of responsibility to themselves or their spouses and in their formulation of the nature of parental deficiencies. PMID- 4016661 TI - Civil commitment trends in Ontario: the effect of legislation on clinical practice. AB - The rationale for and history of civil commitment legislation in Ontario are reviewed. The civil commitment rate in Ontario from 1926 to 1980 for provincial psychiatric hospitals, and from 1974 to 1980 for all psychiatric inpatient facilities was analyzed to detect variation in the rate over time and with relevant legislation. The findings indicate that mental health legislation has had little effect on commitment practices in Ontario. In addition, the variation in the commitment rate over the period reviewed cannot be ascribed to inconsistent application by physicians. The other variables affecting the rate are discussed in this context. The need for more descriptive studies of the major determinants of the commitment rate is emphasized. PMID- 4016662 TI - Depressed children of depressed parents. AB - Fifty children whose parents had a diagnosis of affective disorder were given a structured diagnostic interview by a child psychiatrist. The parents were also interviewed about their children. Fourteen per cent of the children were found to be depressed. Compared to the remaining children, the depressed children endorsed significantly more symptoms of attention deficit disorder, oppositional disorder, mania, overanxious disorder, phobia, and bulimia in the interview. The parent's interview disclosed that the depressed children were abused significantly more than the non-depressed group. PMID- 4016663 TI - [Manic decompensation]. AB - The author stresses early detection of the premonitory signs of a manic breakdown with a view towards an efficient therapeutic intervention. Some of the most typical signs are described with their corresponding dynamic implication. The manic-depressive's lack of impulse control often forces a member of the patient's circle to take control. After a review of the main personality traits belonging to the manic-depressive patient, the author gives a description of the patient's spouse in whom appear similar and complementary elements of the patient's personality. Finally, some steps are suggested to rationalize treatment. Emphasis is on educational methods combined with lithium therapy within the framework of a therapeutic relationship where the interactive dynamic forces are acknowledged. PMID- 4016664 TI - Suicide attempters, ideators and risk-taking propensity. AB - The personality dimensions related to risk-taking propensity in suicide patients were sought. Two dimensions, responsibility and self-esteem, were helpful in distinguishing between suicide involved patients, and non-suicide related cases. PMID- 4016666 TI - Electroconvulsive therapy in a major teaching hospital: diagnoses and indications. AB - The use of ECT over an eleven year period in the University of Alberta Hospitals is reviewed. Five percent of patients received ECT, the mean number of treatments per course was 5.2, and the most frequent type of treatment was bilateral ECT. Discharge diagnoses showed that three-quarters of the patients had affective psychoses and one-fifth were schizophrenic. All patients had had a mandatory consultation before treatment and the most frequent reasons for choosing ECT were given as: failed antidepressant treatment, previous good response to ECT, failure to respond to other treatment, uncontrollable delusions or psychotic behavior, acute suicidal risk requiring a rapid response, and adverse reaction to medication. The mandatory consultation process has worked well and has helped to clarify the situations where ECT may be used with benefit. It is hoped that this may assist those who may be responsible for defining guidelines for the use of ECT. PMID- 4016665 TI - Hysterical seizures as a manifestation of "depression" in old age. AB - A case of hysterical seizures is presented which is ultimately diagnosed as depression and treated successfully with tricyclic antidepressants. The need to re-examine our understanding of illness and the effect of classification on treatment decisions is emphasized. PMID- 4016667 TI - Electroconvulsive therapy. PMID- 4016668 TI - Neoadjuvant (preoperative) chemotherapy for breast cancer. AB - Despite recent developments in the treatment of breast cancer, metastatic breast cancer remains an incurable disease. Postoperative adjuvant treatment may improve the survival of a subgroup of node positive, Stage II breast cancer patients, but the proportion of failures is still high. Preoperative adjuvant chemotherapy, an example of a new approach in scheduling of available agents, is based on sound theoretical and experimental principles. In this report, the authors summarize the background data on the rationale for preoperative adjuvant chemotherapy and present preliminary results of this study in which preoperative treatment starting with one course of cyclophosphamide, methotrexate, and 5-fluorouracil (CMF) was given to newly diagnosed patients with breast cancer. Analysis of the first 43 patients given such treatment has shown that the side effects were comparable to those seen in patients treated with conventional postoperative chemotherapy, and that the delay time between diagnosis and starting chemotherapy has been substantially reduced compared to the historic group of patients. Additional aspects of this study include the introduction of fine-needle aspiration as the only diagnostic method for obtaining the tissue diagnosis of breast cancer, as well as a more intensive interaction between the surgeons from private practice and the oncology institute. PMID- 4016669 TI - Chemohormonal therapy for advanced breast cancer with tamoxifen, adriamycin, and cyclophosphamide (TAC). AB - Combined chemohormonal therapy is an attractive therapeutic strategy for the treatment of Stage IV breast cancer. Between 1977 and 1979, the authors evaluated a new chemohormonal therapy program in 63 evaluable women with advanced breast cancer who previously had not received cytotoxic chemotherapy or tamoxifen. The chemohormonal therapy consisted of 21- to 28-day cycles of tamoxifen (10 mg orally twice daily), Adriamycin (doxorubicin) (40 mg/m2 intravenously on day 1) and cyclophosphamide (200 mg/m2 orally on days 3-6) (TAC). Objective responses were observed in 82% of the patients (22% complete response, 60% partial response). With a median follow-up of 104 weeks (2 years), the median relapse free survival for the 52 responding patients was 80 weeks. The median survival for the entire group of 63 patients was 118 weeks. Eleven pretreatment patient characteristics were evaluated via univariate and multivariate analysis to determine their effect on response and survival. Prognostic factors with a significant association with longer survivals were as follows: a lack of soft tissue involvement, a lack of pleural involvement, and a long disease-free interval (DFI). Estrogen receptor (ER)-unknown patients, being composed primarily of postmenopausal patients with a long DFI and single-organ involvement (primarily bone), comprised 62% of the patient population and achieved a survival similar to the smaller number of ER-positive patients and was superior to the survival of ER-negative patients. Toxicities were recorded on all patients and overall the treatment was well tolerated. Combined chemohormonal therapy with TAC resulted in a high objective response rate and a long median survival. This study would support additional trials of chemohormonal therapy in patients with ER positive tumors or in those whose tumors are likely to be ER-positive (e.g., postmenopausal patients with long DFIs). PMID- 4016670 TI - Non-Hodgkin's lymphoma of Waldeyer's ring and nasal cavity. Clinical and immunologic aspects. AB - Twenty-nine cases of non-Hodgkin's lymphoma of Waldeyer's ring (W-NHL) and nasal cavity or paranasal sinus (N-NHL) were studied for tumor-surface marker phenotype and histopathologic correlation with clinical features. Immunostaining procedures on tissue sections by using xenoantisera and monoclonal antibodies to human B- and T-cells enabled the authors to demonstrate precise surface marker phenotypes of tumor cells and, moreover, the histologic localization of normal or neoplastic B- and T-cells in preserving the original structure of lymphoid organs or tumor tissues. In 22 cases of W-NHL, 19 (86%) had B-cell markers and 3 (14%) had T-cell markers, whereas 6 of 7 cases (86%) of N-NHL had T-cell markers. Tumor cells in T cell lymphomas in W-NHL and N-NHL reacted with antibodies to peripheral T-cells except one case of W-NHL. Rappaport "histiocytic" subtype was heterogeneous with respect to both surface marker characteristics and morphologic features, i.e., seven had B-cell markers and four had T-cell markers, and they were all subdivided into "large cell" or "large cell, immunoblastic" in Working Formulation and "large cell" or "pleomorphic" in Lymphoma Study Group classification. The actuarial survival curve for all T-cell lymphoma patients was characterized by a rapid initial decline and a subsequent plateau, which contained two of the long survivors. In contrast, the B-cell lymphoma group had a more graded decline. The median and actuarial survivals of the T-cell lymphoma group were far inferior to those for the lymphoma group that expressed B-cell markers. PMID- 4016672 TI - Primary pulmonary lymphoma. A clinical and immunohistochemical study of six cases. AB - Six patients with lymphomatous lesions primarily involving the pulmonary parenchyma were studied. In these patients, both the history and physical findings were vague and minimal. The laboratory findings also were nonspecific, although the findings of large multiple lesions in the lungs and pleural adhesion or effusion were more consistent with lymphoma. Histologic examination revealed lymphocytic infiltration of the pulmonary parenchyma in all six patients and presence of germinal or growth centers in some areas of the lesions in four. The hilar or mediastinal lymph nodes were not involved in five patients so examined. Immunocytochemical study of cytoplasmic immunoglobulin revealed monoclonal lymphocytic proliferation in five patients and negative staining in one patient. Clinical, histologic, or immunohistochemical studies alone may not be sufficient to detect all of the lymphomatous lesions. The combined use of all of these parameters is more advantageous for accurate diagnosis of these lesions. Treatment is surgical resection. Radiotherapy or chemotherapy are used when residual disease is present after surgery. Three patients died of disseminated lymphoma 96, 42, and 8 months after diagnosis, respectively, and three patients are still alive at 18, 24, and 4 months, respectively. PMID- 4016671 TI - Expression of blood-group-related antigens in carcinoma in situ of the urinary bladder. AB - Expression of epithelial ABH blood group antigens and the T (Thomsen Friedenreich)-antigen was quantitatively studied by immunoperoxidase techniques in nine cystectomy specimens containing extensive carcinoma in situ (CIS), and also histologically benign epithelium. CIS areas typically showed abnormal expression of both ABH and T-antigens and a distinctive vascular architecture, revealed by endothelial ABH staining. Histologically normal epithelium generally was antigenically normal, but occasionally showed abnormalities of either ABH or T-antigens. Antigen expression was variable in histologically atypical epithelium, with significant segments showing abnormalities of either ABH or T antigen, and sometimes of both antigenic markers. It is postulated that histologically benign, but antigenically abnormal, epithelium may represent low grade CIS of the urinary bladder. Assessment of blood-group-related antigen expression in flat atypical epithelium of the urinary bladder may be useful for predicting the biologic potential of these lesions. PMID- 4016673 TI - Primary lymphomas of the nasal cavity and paranasal sinuses. AB - Extranodal lymphomas which present in the nasal cavity and/or the paranasal sinuses are rare. Thirty-eight patients with disease that was clinically limited to the head and neck (Ann Arbor Stages IE-IIE) were admitted between 1947 and 1983. Twenty-eight patients were treated with radiotherapy alone and 10 received combination chemotherapy in addition. The overall 5-year survival figure was 56%. The corresponding result for Stage IE was 67%. No patient with Stage IIE disease survived 5 years. Extent of the extranodal disease also influenced results for Stage IE patients who were treated with radiotherapy only. When the extranodal disease was staged using the American Joint Committee TNM system, the 5-year disease-free survival for T1 and T2 patients was 78% as compared with 19% for patients with T3 and T4 disease. The addition of combination chemotherapy improved results for patients with T3 and T4 lesions. PMID- 4016674 TI - Primary and secondary tumors of childhood involving the heart, pericardium, and great vessels. A report of 75 cases and review of the literature. AB - Between 1919 and 1981, 16 children with primary cardiac tumors (8 rhabdomyomas, 5 fibromas, 2 myxomas, and 1 rhabdomyosarcoma) and 59 children with secondary tumors of the cardiovascular system were seen at The Hospital for Sick Children in Toronto. Distant metastases in 45 children of the latter group, in descending order of frequency, were from non-Hodgkin's lymphoma, neuroblastoma, soft tissue and bone sarcoma, Wilms' tumor, and hepatoma, and involved the myocardium and pericardium. In the remaining 14 children, tumor thrombi from Wilms' tumor (9 cases), adrenal (2 cases) and hepatocellular carcinoma (2 cases), and endodermal sinus tumor (1 case) extended directly into the great veins and/or cardiac chambers. Children with primary and secondary tumors often present with nonspecific clinical, plain radiographic, electrocardiographic, and M-mode echocardiographic findings. Early recognition, utilizing special diagnostic procedures such as two-dimensional echocardiography, computerized axial tomography, angiocardiography, and inferior venocavography, followed by elective surgical resection of tumor under cardiopulmonary bypass and/or radiation and chemotherapy, offers patients with cardiovascular tumors the best chance of cure. PMID- 4016675 TI - Esophagitis and cancer of the esophagus. AB - Early diagnosis is an important factor in the effort to increase the healing rates of esophageal cancer; another consideration is the establishment of a reliable method of identifying risk groups. Alcohol abuse is known to be associated with a higher risk of esophageal cancer. The current investigation, based on a retrospective study of the records of patients with esophageal cancer, reveals a strong connection between cancer development and chronic esophagitis due mainly to reflux in about 10% of the patients. In the literature this connection has been suspected but never so clearly shown. The clinical implication may be a more rigorous approach to long-standing esophagitis in elderly patients. PMID- 4016676 TI - Alveolar rhabdomyosarcoma of the female genitalia. AB - Eight cases of alveolar rhabdomyosarcoma of the female genitalia were diagnosed from 1963 to 1983 at The University of Texas M. D. Anderson Hospital. The primary sites were vulva in two, perineum in five, and broad ligament in one patient. When possible, therapy was initiated with local tumor excision (five patients). Surgery was followed by local or regional radiation (six patients) and chemotherapy (seven patients). Of the eight patients, five died within 9 months, one died 27 months after diagnosis, and only two are 5-year survivors. The aggressive behavior of this tumor is evidenced by autopsy findings of widespread metastases. Metastatic disease to the bone was present in four patients and to the breast in three patients. Local disease was controlled in two patients who died of distant metastases. Current therapy recommendations include excisional surgery, local radiation, and combination chemotherapy. A need for more effective chemotherapeutic programs is evident. PMID- 4016677 TI - Laparotomy-staged IA versus IIA Hodgkin's disease. A comparative study with evaluation of prognostic factors for stage IIA disease. AB - Ninety-one laparotomy-staged (LAP) IA and IIA Hodgkin's disease (HD) patients were analyzed to evaluate the prognostic significance of stage, mediastinal status, extranodal disease and histology. Forty IA patients were treated with radiotherapy (XRT) only; of 51 IIA patients, 44 received XRT only and 7 had additional chemotherapy. Disease-free survival (DFS) at 5 and 10 years was 81% and 70%, respectively, with overall survival (S) of 93% and 86%, respectively. Disease-free survival for IA patients (93% at 5 and 10 years) was significantly superior to IIA (73% at 5 years, 52% at 10 years). Survival differences were not statistically significant. For IIA patients receiving XRT only, large mediastinal disease was an adverse factor for DFS. Small mediastinal disease in IIA was significantly better than no mediastinal disease. For the whole group of LAP IA and IIA treated by XRT only, three prognostic groups were identified: (1) Stage IA and Stage IIA with mediastinal disease, but less than 7.5 cm in width was highly favorable with less than 10% relapse; (2) Stage IIA nonmediastinal had an intermediate prognosis with relapse in about 33%; (3) Stage IIA large mediastinal (greater than or equal to 7.5 cm) had an unfavorable DFS with relapse in about 55%. The third group contained a highly unfavorable subset with mediastinal masses greater than 10 cm, all of whom relapsed. Salvage therapy was successful in 60% of relapsing patients. In the context of relatively effective salvage therapy, the role of adjuvant chemotherapy in adverse prognostic groups is discussed and it is concluded that the only clearly justifiable use for adjuvant chemotherapy is in patients with massive (greater than 10 cm) mediastinal adenopathy. PMID- 4016678 TI - Renal glomerulopathies associated with Hodgkin's disease. AB - From a series of 138 patients with Hodgkin's disease seen over a 17-year period, 2 developed the nephrotic syndrome. One patient developed hematuria unrelated to cytotoxic chemotherapy or thrombocytopenia. All three patients had evidence of glomerulopathy on histologic examination of renal tissue, but none had the more usually associated minimal-change glomerular histologic features. The patients with nephrotic syndrome had effective clinical regression with systemic chemotherapy. The significance of renal glomerular disease in association with Hodgkin's disease is discussed. PMID- 4016679 TI - Angiofollicular lymph node hyperplasia (Castleman's disease) associated with vertebral destruction. AB - A 45-year-old man presented with lower thoracic pain, proteinuria, and destruction of thoracic vertebra from an adjacent unresectable paraspinal mass which, on biopsy, demonstrated angiofollicular lymph node hyperplasia (AFLNH). The patient received 3939 rad in 22 fractions to the mass and associated area of vertebral destruction. The patient is currently asymptomatic without recurrence of pain or progression of neurologic symptoms 5 years after radiotherapy. There has been resolution of the previous proteinuria. Serial computerized tomography scans and x-rays show no change in the paraspinal mass nor resolution of the vertebral destruction adjacent to the mass. A search of the English literature has failed to identify any previous association of AFLNH and bone destruction. PMID- 4016680 TI - Sites of primary malignancies in patients presenting with cerebral metastases. A review of 120 cases. AB - A retrospective study is reported of 120 consecutive cases of patients presenting with brain metastases as the primary sign of their malignancy. Primary site was found in 62 patients (53 while alive and 9 at postmortem examination) and remained unknown in 58. Lung was the most frequent primary site (45% of known sites), and digestive malignancies were surprisingly the second most frequent primary site (19% of known sites), whereas breast was found in less than 5%. When primary site was disclosed, in 85% it was after history, clinical exam, chest x ray, and pathologic findings. Survival was almost identical in both known and unknown primary sites: 54% versus 44% at 6 months, 20% versus 16% at 1 year, and 6% versus 5% at 2 years. It was concluded that extensive evaluations to identify primary sites do not appear to be rational in patients presenting with brain metastases. PMID- 4016681 TI - Myxopapillary ependymoma. A clinicopathologic and immunocytochemical study of 77 cases. AB - The study involved 77 myxopapillary ependymomas of the spinal cord encountered during a 60-year period (1924-1983). This variant of ependymoma was, with few exceptions, limited to the lumbosacral region, particularly the filum terminale. The male:female ratio was 1.7:1, and the mean age at diagnosis was 36.4 years (range, 6-82); at presentation, 15 (19%) of the patients were in the first two decades of life. The duration of symptoms ranged from 1 month to 30 years; the most frequent complaint was low-back pain, and eight patients had undergone prior "disc surgery." Generally, myelographic block was disclosed. Preoperative cerebrospinal fluid protein levels averaged 2462 mg/dl. Myxopapillary ependymomas are slow-growing tumors that show no significant tendency to histologic dedifferentiation. Despite some variation in cytologic features and the presence of atypia and modest mitotic activity in most cases, the gross characteristics of the tumors appear to be of greater prognostic significance than the histologic features. Tumors that were encapsulated (25%) and amenable to intact, total surgical removal had a recurrence rate of 10%, whereas those that were removed either piecemeal (34%) or subtotally (41%) had recurrence rates of 19%. Overall survival, however, was more closely related to residual disease; total removal of tumor, whether intact (encapsulated) or piecemeal, resulted in longer survival (19 years) than did subtotal resection (14 years). Patients who died (6.5%) did so after a prolonged course marked by multiple recurrences. Radiotherapy may be of particular benefit to patients whose tumors are not amenable to intact total removal. PMID- 4016682 TI - Age as a prognostic factor in breast cancer. AB - Long-term survival was evaluated in a total of 12,319 women with first breast cancer, comprising 94.9% of virtually all women with first breast cancers diagnosed in Sweden in 1959 through 1963. After correction for the expected mortality, it was found that age at diagnosis was an important predictor of the probability of escaping the risk of dying of breast cancer (relative survival), with a regular trend toward a more favorable course in younger women. This difference between the age groups is apparent as early as 5 years after diagnosis and increases throughout the period of observation. Thus the relative 20-year survival rates +/- 95% confidence limits were 51.3 +/- 3.8%, 41.2 +/- 3.4%, 34.2 +/- 3.8%, and 16.6 +/- 6.3% at ages 40 through 44, 50 through 54, 60 through 69, and 70 through 79 years, respectively. Patients younger than 40 years diverged from the general trend, with a survival rate of 44.1 +/- 4.6% at 20 years. PMID- 4016683 TI - The malignant pleural effusion. A review of cytopathologic diagnoses of 584 specimens from 472 consecutive patients. AB - This study reports the cytopathologic diagnoses rendered on all malignant pleural effusions received and processed over a period of 14 years. Specimens of fluid from various body sites (25,464) were examined. Of these, 5888 (23%) were specimens of pleural effusions. Five hundred eighty-four specimens (9.9% of total pleural fluid specimens) taken from 472 patients were diagnosed as containing cancer cells. Of the malignant pleural effusions, 75.7% were classified as carcinomatous in type. Adenocarcinomas comprised 47.4% of the 584 specimens. The groups of large cell undifferentiated carcinoma and lymphoma/leukemia approximated one another in being the second most common cancer groups (14.3% and 15.0%, respectively). For both males and females, the frequency of organ site or primary tumor type was lung (35.6%), lymphoma/leukemia (15.9%), breast (14.8%), female genital tract (8.1%), and gastrointestinal tract (5.9%). Among male patients, the order of frequency was lung (49.1%), lymphoma/leukemia (21.1%), gastrointestinal tract (7.0%), genitourinary tract (6.0%), and malignant melanoma (1.4%). In female patients, the order of frequency was breast (37.4%), female genital tract (usually ovary) (20.3%), lung (15.0%), lymphoma/leukemia (8.0%), and gastrointestinal tract (4.3%). In 48 patients (10.2%) the primary site of neoplasm was never determined. In 90.5% of patients a cytopathologic diagnosis conclusive for cancer was obtained on the first specimen of fluid. There were no false positive diagnoses. PMID- 4016684 TI - Radical retroperitoneal tumor surgery with resection of the psoas major muscle. AB - Three patients with extensive retroperitoneal cancer are presented, in whom the psoas muscle was resected as part of a radical tumor excision. The resection of the psoas muscle, including the femoral nerve, which travels in its substance, and the genitofemoral and ilioinguinal nerves, caused little morbidity (denervation weakness of the quadriceps and anterior high numbness) and improved the quality of the excision. Ablation of the psoas muscle is technically possible; it may improve the patient's outlook both for palliation and for curative intent. PMID- 4016685 TI - Hereditary nonpolyposis colorectal cancer (Lynch syndromes I and II). I. Clinical description of resource. AB - Hereditary nonpolyposis colorectal cancer (HNPCC) is comprised of the following: the cancer family syndrome (CFS), or Lynch syndrome II, which shows early-onset proximal colonic cancer predominance and other associated extracolonic adenocarcinomas, particularly endometrial carcinoma; and hereditary site-specific colon cancer (HSSCC), or Lynch syndrome I, which shows all of the same characteristics, except for extracolonic cancer. Nine families with CFS and two with HSSCC provided the resource that was tested for biomarkers (see companion article). All families were meticulously evaluated for genealogy and cancer verification. Biologic specimens were obtained during field visits to areas of closest geographic proximity to the families. Cancer education and recommendations for surveillance/management were provided to patients and their physicians. Additionally, 40 families (about 3000 individuals) with either CFS or HSSCC have been ascertained. Syndrome cancers were restricted to direct-line relatives as opposed to nonbloodline relatives, arguing against involvement of environmental factors. One documented clinical feature was a predilection for proximal versus distal colonic cancer in both CFS and HSSCC kindreds. This has important clinical significance in that it clarifies the need for instituting effective surveillance earlier to detect the predominantly proximal colonic cancers. PMID- 4016687 TI - The role of gender and other factors in the prognosis of young patients with colorectal cancer. AB - Fifty patients from a socioeconomically disadvantaged population who were diagnosed when younger than 40 with colorectal cancer between 1968 and 1978 were analyzed. These patients had an increased survival compared with their older counterparts aged 40 years and older who were diagnosed during the same time. The young women had significantly better survival than the young men. Advanced stages, distribution of primary sites, and precancerous conditions were not major factors. The fact that the younger patients' cancers had a higher incidence of extracellular mucin production may have been counterbalanced by their receiving more extensive treatment. At the same time, cultural and social factors related to gender may have more to do with better survival than do factors evaluated in previous studies. In fact, because of the pervasive lack of male/female analysis, it is not known whether the survival difference due to gender found in this report is a universal tendency in young populations. PMID- 4016686 TI - Hereditary nonpolyposis colorectal cancer (Lynch syndromes I and II). II. Biomarker studies. AB - Nine families with the cancer family syndrome (CFS), or Lynch syndrome II, and two with hereditary site-specific colonic cancer (HSSCC), or Lynch syndrome I, were investigated for the following potential biomarkers of genotype status: in vitro tetraploidy of dermal fibroblast monolayer cultures; tritiated thymidine uptake (3HdThd) labeling of colonic mucosa; cytogenetics of peripheral blood mononuclear leukocytes; quantitative serum immunoglobulin determinations; methionine dependence in dermal fibroblasts in tissue culture; segregation analysis; and the study of gene linkage with respect to 25 landmark serum and blood group markers. Positive lod scores of 3.19 for linkage of the Jk (Kidd blood group) with CFS were obtained. Both in vitro tetraploidy and 3HdThd uptake in the distal colonic mucosal crypt compartments were positively associated with cancer risk status in CFS and HSSCC kindreds. There was a high incidence of polymorphisms of centromeric heterochromatin, including complete inversion. These findings are of particular clinical and genetic significance because HNPCC lacks premonitory signs of cancer risk. If confirmed, they could conceivably enable definition of genotype as early as birth in members of HNPCC kindreds, thereby enabling psychologic preparation and intensive cancer education for improved compliance in surveillance/management programs. These studies also provide new clues about the chromosome(s) bearing the presumed cancer gene(s). For example, CFS gene(s) may possibly be located on chromosome 2, where Jk is located. These biomarkers merit intensive study in additional HNPCC kindreds for a more complete assessment of their sensitivity and specificity. Additionally, essential aspects of previous reports involving biologic samples from these and/or similar subject kindreds are included to permit a comprehensive presentation of the combined findings of this consortium to date. PMID- 4016688 TI - Therapeutic implications of the natural history of advanced cervical cancer as defined by pretreatment surgical staging. AB - From 1978 to 1983, 112 women with advanced cervical carcinomas received radiotherapy after pretreatment surgical staging. Five-year actuarial relapse free survival rates were a strong function of lymphatic spread: 40% with periaortic node metastases, 50% with pelvic node metastases, and 84% without node metastases. Primary treatment failure had a distant component in 75% of recurrences (50% of recurrences with negative nodes and 85% of recurrences with positive nodes). It was concluded that adjuvant systemic therapy is necessary to substantially raise the probability of cure. PMID- 4016689 TI - The effect of transurethral prostatic resection on the incidence of osseous prostatic metastasis. AB - Of 169 patients with a minimum of 4 years follow-up treated definitively with irradiation for adenocarcinoma of the prostate, 100 had transurethral prostatic resection (TURP) before treatment. In comparing that group with the group who did not have TURP, osseous metastases developed in 28% versus 22%, respectively. Further stratification by tumor grade and stage failed to show TURP-dependent tumor dissemination, whereas the incidence of bony metastasis increased progressively with decreasing tumor differentiation and advancing tumor stage. PMID- 4016690 TI - The role of social support systems in adolescent cancer amputees. AB - Amputation is often a component in the treatment of bone tumors such as osteogenic sarcoma, which is most prevalent in the adolescent age group. Adaptation to cancer and loss of a limb requires a significant multidimensional effort. To examine the role of social support systems, 27 adolescents who had undergone amputations for cancer were interviewed. Inquiries were made regarding patients' perceived social support providers and the impact of amputation upon their lives and independence. Parents, especially mothers, were perceived as realistic and most helpful at the time of surgery (80%), followed by professional hospital staff (59.3%), and siblings (59.3%). Friends of patients were less helpful, as many reported their friends felt sorry for them (65.4%), avoided them (33.3%), or drifted away (40%). Only 7.4% of the patients had a clear preference to be associated with other amputees. This study details other preferences and difficulties encountered by the adolescent amputees and the role of support systems in their adaptation to their disease and amputation. PMID- 4016691 TI - Non-Hodgkin's lymphoma in northern India. A retrospective analysis of 238 cases. AB - A retrospective analysis was performed of 238 patients, aged 12 years and older, with non-Hodgkin's lymphoma presenting to the All India Institute of Medical Sciences, New Delhi, India, between September 1975 and December 1982. Pathologic material was reviewed and classified according to the modified Rappaport classification. The most common histologic type encountered was diffuse histiocytic lymphoma (39%), followed by diffuse poorly differentiated lymphocytic lymphoma (29%), and diffuse mixed histiocytic and lymphocytic lymphoma (9%). Nodular lymphomas constituted 9% of all non-Hodgkin's lymphomas. A lower frequency of nodular lymphomas, a lower median age of onset (45 years), and a higher male to female ratio (4.5:1) as compared with Western countries was observed. Survival information on 90 patients revealed no effect of age, sex, stage of disease, and "B" symptoms on survival, whereas histologic diagnosis had a significant influence on survival (P less than 0.05). A median survival of 24 months in 58 patients receiving chemotherapy is comparable to that reported by other investigators. PMID- 4016693 TI - Multiagent chemotherapy for sarcoma diagnosed during pregnancy. AB - A 21-year-old, gravida 1, para O, woman presented at approximately 25 weeks gestation with a large Ewing's sarcoma involving her iliac wing. She was treated with multiagent chemotherapy before a successful Cesarean delivery of a normal infant at approximately 34 weeks gestation. Four years later both the mother and child are doing well. The literature regarding sarcoma occurring during pregnancy and that regarding multiagent chemotherapy in pregnant patients is reviewed. Chemotherapy should be instituted early in the course of many malignant sarcomas, despite pregnancy, to prevent the occurrence of metastases. PMID- 4016692 TI - Preoperative intra-arterial infusion chemotherapy for advanced squamous cell carcinoma of the mouth and oropharynx. AB - Twelve patients with advanced locoregional (Stage III and IV) squamous cell carcinoma of the oral cavity and oropharynx underwent treatment with cisplatin, vinblastine, bleomycin, and 5-fluorouracil, given by intra-arterial infusion, as primary adjuvant therapy, in preparation for radiation therapy and surgery. Responses were observed during or immediately after infusion therapy in 8 of 12 (67%) of patients (1 complete response, 7 partial responses). Infusion chemotherapy was followed by radiation therapy alone in five patients and by radiation and surgery in six patients. The protocol was initiated in August 1981, and six patients are now free of their primary cancer, at 21 to 36 months, whereas six have died with disease. Arterial infusion of a combination of effective antineoplastic agents is a promising method for the preparation of selected patients for radiation therapy and surgery, as it is less likely to produce serious systemic toxicity and it requires a shorter period than systemic neoadjuvant chemotherapy. PMID- 4016694 TI - Anticancer drug activity in human bladder tumor cell lines. AB - A panel of ten human bladder tumor cell lines were tested for drug sensitivity to ten standard or investigational anticancer drugs using a tumor colony assay. The activity of these anticancer agents in vitro was then compared with the clinical activity of these agents in bladder cancer. Drug activity was found in only five of the ten cell lines. In only 9 of 100 drug assays was the inhibition of colony growth lower than 30% of the controls. The activity of the more active anticancer drugs in bladder cancer (i.e., methotrexate and cisplatin) was not predicted using the tumor colony assay. Overall, the low level of activity of most anticancer drugs tested paralleled the clinical experience of drug resistance found in human bladder cancer. PMID- 4016695 TI - Locally recurrent hypernephroma treated by radiation therapy and embolization. A report of two cases. AB - Two patients who underwent radical nephrectomy for renal cell carcinoma developed local recurrence with lumbar vertebral involvement and intractable pain. Both patients were treated with a combination of radiation therapy and selective lumbar vertebral artery embolization with complete resolution of pain and no evidence of recurrence of disease after 3 years. PMID- 4016696 TI - Squamous cell carcinoma of the head and neck after radiation therapy for Hodgkin's disease. A report of two cases and a review of the literature. AB - Squamous cell carcinoma (SCC) of the head and neck developed in two patients 12 and 22 years, respectively, after radiation treatment for Hodgkin's disease (HD). Both tumors arose in previously irradiated fields. Sixteen reported cases of SCC of the head and neck occurring after treatment for HD are summarized. Details of treatment were lacking in most instances. The authors suspect that cases similar to the two reported here will be seen more frequently with longer follow-up of patients cured of HD. PMID- 4016697 TI - Effects of preparatory patient education for radiation oncology patients. AB - Sixty cancer patients undergoing their first course of radiotherapy were assigned to one of two patient education conditions as they entered treatment: patients in the high-information condition were shown an audiovisual program, presenting procedural and sensory information about radiotherapy; patients in the low information condition received standard care without exposure to the patient education program. On the basis of psychologic testing, patients were also classified on "vigilant-avoidant" and "repression-sensitization" coping style dimensions. Outcome variables, assessed during the first and last weeks of treatment (T1 and T2, respectively) induced ratings of treatment-related knowledge, state anxiety, and total mood disturbance. Preparatory patient education produced positive results regardless of coping style. Patients in the high-information condition showed significantly greater treatment-related knowledge (at T1) and less emotional distress (at T2). There was no significant main effect for coping style, nor was there an interaction effect (coping style by intervention condition). Results are discussed in terms of the manifest need for preparatory information in radiation therapy settings, the role of coping style factors, and the clinical utility of patient education interventions. PMID- 4016698 TI - Fiber concentration in lung tissue of patients with malignant mesothelioma. A case-control study. AB - The risk of malignant mesothelioma associated with low-level asbestos exposure is an important unresolved issue today. We have analyzed the asbestos fiber concentration in lung tissue from 14 cases of malignant mesothelioma and 28 case matched controls by scanning electron microscopy. The cases represent 86% of all mesotheliomas recorded by the Cancer Registry of Norway from the county of Hordaland between 1970 and 1979. Based on 1 million fibers per g of dried tissue as an indicator of cumulated asbestos exposure, the odds ratio (relative risk) was 8.5 (95% confidence limits, 2.3-31.1). Assuming that the risk of malignant mesothelioma is related to mineral fiber concentration in lung tissue, it is concluded that a fiber concentration exceeding 1 million fibers per g of dried tissue is associated with an increased risk of malignant mesothelioma. Furthermore, the results are consistent with a no-threshold response. PMID- 4016699 TI - Study of the cell proliferation kinetics in ulcerative colitis, adenomatous polyps, and cancer. AB - Cell proliferation kinetics, using autoradiography, was investigated in 4 specimens of normal colonic mucosa, 11 cases of ulcerative colitis, 15 adenomas, and 17 advanced cancers of the large intestine. In the normal mucosa, the labeled cells were located only in the lower three fifths of the crypts, the so-called proliferation zone, and their labeling index was 11.7 +/- 4.0%. In the ulcerative colitis, the proliferation zones were remarkably extended toward the upper part of the crypts, and the mean labeling index was 20.5 +/- 9.4%. In the adenomatous polyps, labeling was seen in any part of the crypts, and abnormal proliferation patterns such as denseness, stratification, expansion, and budding of the labeled cells tended to increase in accordance with the degree of the histologic atypism. Their mean labeling index was 22.2 +/- 8.6%. However each labeling index of the polyps increased proportionally to their histologic atypism, from 15.2 +/- 8.1% in grade II to 30.1 +/- 9.9% in grade V. The mean labeling index of the cancers was 23.3 +/- 9.6%, and there was little difference in the labeling patterns of the malignant polyps and cancers. The proliferation patterns of the polyp and cancer were qualitatively different from those of the normal mucosa and the ulcerative colitis. PMID- 4016700 TI - Prognostic and therapeutic use of microstaging of cutaneous squamous cell carcinoma of the trunk and extremities. AB - Cutaneous squamous cell carcinomas (SCC) arising in actinically damaged skin, unassociated with chronic inflammation or injury, are generally regarded as nonaggressive lesions. These tumors occasionally recur or metastasize, however, as do de novo SCC. The authors reviewed 63 patients with cutaneous SCC of the trunk or extremities, excluding lesions that developed in known high risk settings, in order to explore the potential of histologic microstaging as a prognostic indicator. Fifty-four patients (86%) were free of recurrence following primary surgical therapy. Nine patients (14%) had either local recurrence or metastases; five of these (8% of the entire series) died of their tumors. Tumor behavior correlated best with the level of dermal invasion and the vertical tumor thickness. All tumors that recurred were 4 mm or more thick and involved the deep half of the dermis or deeper structures. All tumors that proved fatal were at least 10 mm in maximum thickness, and the four lethal lesions that could be evaluated for level of invasion extended into subcutaneous tissue or deeper structures. The thickness and level of invasion of cutaneous SCC appear to represent important prognostic factors and may be relevant indicators for wide field resection and/or elective lymph node dissection. PMID- 4016701 TI - Cerebral pilocytic astrocytoma. AB - Cerebral pilocytic astrocytoma is a known intracranial tumor, but its biological characteristics are less well documented. The authors report 30 patients with cerebral pilocytic astrocytoma who were accessioned by the Armed Forces Institute of Pathology between 1970 and 1980. Histological appearance of the tumor was correlated with clinical characteristics. Mean age of onset was 22.15 years, mean preoperative duration of symptoms was 3.77 years, and mean postoperative survival was 5.91 years, with 20 of 23 (87%) known to ultimately survive surgery. These cases of cerebral pilocytic astrocytoma exhibited histologic characteristics consistent with that of a low-grade tumor. Although several of these tumors were of guarded prognosis due to location, degree of infiltration or cyst recurrence, they generally demonstrated a natural course of a relatively low-grade neoplasm. PMID- 4016702 TI - Neoplastic angioendotheliosis. Immunohistochemical and electron microscopic findings in three cases. AB - Three cases of neoplastic angioendotheliosis (NAE) presenting with central nervous system (CNS) disease but no skin lesions are described. The histogenesis of the neoplastic cells is discussed. Microscopic examination showed accumulation of neoplastic cells in the vascular system throughout the body and their extravascular proliferation in several organs. Electron microscopic and immunohistochemical studies revealed the presence of Weibel-Palade bodies and factor VIII-related antigen in intravascular and extravascular neoplastic cells in two of the three cases. In the first case the neoplastic cells did not have any T-cell markers. However, in one case no specific markers were found in the neoplastic cells by electron microscopic, enzyme histochemical, or immunohistochemical examination. These findings, although supporting the endothelial origin of the neoplastic cells, indicate the need for further consideration of whether NAE is actually a single disease entity or several different diseases. PMID- 4016703 TI - Retroperitoneal lymphangioleiomyomatosis. A 36-year benign course in a postmenopausal woman. AB - An 89-year-old asymptomatic white woman was found to have a pelvic mass with retroperitoneal extension. Biopsy of the lesion demonstrated lymphangioleiomyomatosis. Review of her records revealed that 36 years ago a mass in the same location had been found incidentally and biopsy was performed during abdominoperineal resection for rectal carcinoma. Comparison of the old and recent biopsy specimens showed an identical histologic appearance. This case, therefore, represents a benign, localized form of lymphangioleiomyomatosis; the long survival without therapy may be related to the fact that this patient was postmenopausal. PMID- 4016704 TI - Adnexal carcinomas of the skin. II. Extraocular sebaceous carcinomas. AB - Extraocular sebaceous carcinomas are uncommonly seen neoplasms, and have been confused in the past with basal cell carcinomas showing sebaceous differentiation. In contrast to the latter tumors, however, sebaceous carcinomas have a distinct risk of aggressive behavior. This study presents clinicopathologic data on five cases of sebaceous carcinoma arising in cutaneous locations outside of the ocular adnexae. Four of five patients were men, and the average age at diagnosis was 63 years. Three tumors occurred on the face, one arose in the skin of the neck, and another occurred on the penis, an anatomic site that is extremely rare for sebaceous carcinoma. Three tumors metastasized, and two patients died of tumor or with residual tumor growth. In light of this behavior, the premise that extraocular sebaceous carcinomas rarely spread to distant sites may need reexamination. PMID- 4016705 TI - Aspiration cytology in the staging of urologic cancer. AB - Knowledge of the status of the pelvic lymph nodes is vital for accurate staging and adequate treatment of patients with urologic cancer. Noninvasive techniques for assessing the lymphatic spread of urologic neoplasms have proved to be of limited value. Bipedal lymphangiography and percutaneous fine needle aspiration cytology under fluoroscopic guidance were performed for staging purposes in 71 patients with clinically localized bladder, prostatic and penile cancer from 257 nodal chains. The overall diagnostic accuracy was 93% and the correct aspiration of 186 lymph nodes was surgically confirmed. There were 11 (6%) false-negative biopsy results and no false-positive diagnoses. Aspiration cytology is a safe, well tolerated, accurate, and rapid method of determining the presence of metastatic disease in lymphangiographically visualized pelvic nodes. In the management of prostatic carcinoma, positive cytologic results are diagnostic of nodal metastatic involvement and spare the patients unnecessary surgical staging. Negative cytologic findings may be considered diagnostic of localized disease in the patients with well differentiated prostatic carcinoma (2-4 Gleason's sum). Since most surgeons are reluctant to perform a staging lymphadenectomy in the management of invasive bladder carcinoma, aspiration cytology can provide accurate staging, thus permitting an appropriate treatment plan. In patients with carcinoma of the penis, a positive aspirate permits an early and even curative lymphadenectomy in cases with clinically negative but pathologically positive nodes. PMID- 4016706 TI - The Sezary syndrome with rapid pulmonary dissemination. AB - The authors report the case of a patient with long-standing Sezary syndrome who developed the acute onset of bilateral pulmonary infiltration, severe hypoxemia, and hypotension. Initial diagnostic considerations centered around infection, but an open-lung biopsy revealed "mycosis fungoides" without evidence of an infectious process. The patient showed striking improvement when given vincristine and cyclophosphamide, but ultimately died 3 months later of a nonpulmonary catheter-related infection. This rare clinical association stresses the value of open lung biopsy as a diagnostic measure even in desperately ill individuals. PMID- 4016707 TI - Assessment of mandibular invasion by carcinoma. AB - In this prospective study of 31 patients, the most sensitive assessment of malignant invasion of the mandible was by physical examination. Bone scanning and conventional roentgenographs are useful adjuncts in the staging evaluation of patients when clinical involvement is suspected and to determine the extent of disease in order to aid in treatment planning. However, they are frequently subject to false-positive interpretive errors, especially due to increased osteoblastic activity associated with dental disease and occasional tumor adjacent to the mandible. When appropriate, the radiographs ordered should be those that allow for the most accurate assessment of the particular lesion as determined by its location. Until a more specific and accurate method for detecting and measuring malignant invasion of the mandible is developed, the physical findings and the judgment of the head and neck surgeon remains our most valuable tool. PMID- 4016708 TI - Do regular ovulatory cycles increase breast cancer risk? AB - The "estrogen window hypothesis" of the etiology of breast cancer proposes that unopposed estrogen stimulation is the most favorable state for tumor induction and that normal postovulation progesterone secretion reduces susceptibility. The authors believe that epidemiologic and experimental studies suggest rather that the opposite is true, i.e., that breast cancer risk is directly related to the cumulative number of regular ovulatory cycles. Unlike the endometrium, breast tissue mitotic activity is enhanced in the luteal phase of the menstrual cycle. Regular vigorous physical activity is one method of reducing the frequency of ovulatory cycles, and such exercise could markedly reduce a woman's lifetime risk of developing breast cancer. PMID- 4016710 TI - Surgical treatment of distant metastatic melanoma. Indications and results. AB - A retrospective study was made of the surgical treatment of distant metastases from melanoma in 143 patients. The determinants of survival benefit were: (1) successful complete resection of all clinical disease; (2) single versus multiple metastatic site; and (3) anatomic location of disease. Complete resection was achieved with single- and multiple-site lesions in 67% and 31% of the patients, respectively, yielding corresponding 5-year survival rates of 33% and 9%, respectively. Incomplete resection yielded little survival benefit. Soft tissue and extraregional nodal lesions were completely resectable in 70%, whereas pulmonary, extrahepatic abdominal visceral, and osseous lesions were in 40% of the patients, resulting in similar 5-year survival rates of 17% to 22%. The operative mortality rate was 1.4% (2/143). Unsuccessful resection frequently led to very long hospitalization periods for complications and disease, with some patients spending more than 50% of their remaining survival time in the hospital. These observations suggest that, with proper selection of patients, guided by these determinants, surgical resection can offer a reasonable expectation of prolonged survival. PMID- 4016709 TI - Pulmonary metastases in ovarian cancer. Analysis of 357 patients. AB - The pattern of pulmonary involvement from ovarian cancer was evaluated in 357 patients who were seen at the Yale-New Haven Hospital from 1966 to 1975. Thoracic involvement by tumor was found in 169 patients (44.5%), a figure considerably higher than in previous reports. Pleural effusions were present in nearly 75% of patients who had thoracic involvement. Only 73% of the effusions contained identifiable malignant cells. Solid metastases to the pulmonary parenchyma were present in 12.3% of the patients; lymphangitic and nodal spread was observed in only 1% of the patients. The incidence of metastases did not correlate with tumor histologic features. Five-year survival figures were 29% for the control group; 5.6% of the patients who had evidence of thoracic involvement were alive after 5 years compared with a 49% 5-year survival of those patients with no evidence of thoracic involvement. Right-sided lesions produced thoracic metastases more frequently than left-sided lesions. No significant differences with respect to age, race, menopause, smoking history, or autopsy rate were found between those patients with and without pulmonary metastasis. Chest x-ray was found to be of great value in determining pulmonary metastasis; only 6% of patients who were proven by autopsy to have spread of cancer to the thoracic cavity had a chest x ray that did not show malignancy. The majority of these ten patients had lymphangitic or microvascular disease. No cases of second primary occurring in the lung were noted in this review, although two case reports have appeared in the literature. Only three patients with pulmonary involvement by tumor had no other evidence of Stage IV disease. PMID- 4016711 TI - A totally implanted venous access system for the delivery of chemotherapy. AB - The use of an Ommaya Capsule-Catheter System for the delivery of chemotherapy in cancer patients with inadequate peripheral veins has been studied over a 6-year period. Between 1978 and 1984, 76 Ommaya capsules were implanted in 68 patients, providing a collective experience of over 28,000 venous access days. Two patients were lost to follow-up. The results of the capsule-catheter system performance indicates a functional rate of over 90%. The complications included a 6.7% catheter occlusion rate, and a 2.7% capsule leakage rate. This accounts for an overall catheter related complication rate of 9.4%. PMID- 4016712 TI - Hyperthermia-induced vascular injury in normal and neoplastic tissue. AB - The sequential morphologic alterations in normal skeletal muscle in rats, Walker 256 tumors in rats, and transmissible venereal tumors (TVT) in dogs following microwave-induced hyperthermia (43 degrees C and 45 degrees C for 20 minutes), were studied by histologic and ultrastructural examination. Normal muscle and Walker 256 tumors showed edema, congestion, and hemorrhage at 5 minutes post heating (PH), followed by suppuration, macrophage infiltration, and thrombosis at 6 and 48 hours PH, and finally by regeneration and repair by 7 days PH. Vascular endothelial damage and parenchymal degeneration were present 5 minutes PH. Progressive injury occurred for at least 48 hours PH. Two hyperthermia treatments separated by a 30- or 60-min cooling interval, were applied to Walker 256 tumors in a subsequent study. Increased selective heating of tumor tissue versus surrounding normal tissue, and increased intratumoral steady state temperatures were found during the second hyperthermia treatment. Canine TVTs were resistant to hyperthermia damage. These results suggest that vascular damage contributes to the immediate and latent cytotoxic effects of hyperthermia in normal tissue and some types of neoplastic tissue, and that selective heating of neoplastic tissue occurs in tumor tissue with disrupted microvasculature. PMID- 4016713 TI - 14q+ abnormality with probable t(8;14)(q24;q32) in a young Haitian immigrant with acquired immunodeficiency syndrome and concomitant Burkitt's-like lymphoma. AB - Cytogenetic analyses were carried out in a young Haitian immigrant with acquired immunodeficiency syndrome and concomitant Burkitt's-like lymphoma associated with massive bone marrow infiltration. A characteristic 14q+ abnormality was found in all bone marrow cells examined. Although chromosome abnormality involving band 8q24 was not evident in all the cells examined, some karyotypes show that the typical t(8;14)(q24;q32) is most probably present. No other complex rearrangements could be identified. This is the first report of concomitant acquired immunodeficiency syndrome and Burkitt's-like lymphoma in the Haitian community. Our cytogenetic findings provide further evidence for the role of specific chromosomal rearrangements in Burkitt's-like lymphoma oncogenesis in the setting of acquired immunodeficiency syndrome. PMID- 4016714 TI - Analysis of dihydrofolate reductase gene amplification in a methotrexate resistant human tumor cell line. AB - Detailed cytogenetic and molecular biologic studies have been performed on the human KB tumor cell line and four methotrexate-resistant subclones. Results are presented, demonstrating that the gene encoding the target enzyme dihydrofolate reductase is increasingly amplified in progressively methotrexate-resistant subclones, and that dihydrofolate reductase sequences are localized to a homogeneously staining region on chromosome 10q. PMID- 4016715 TI - Karyotypic evolution in multiple myeloma. AB - A patient with IgG kappa multiple myeloma was studied cytogenetically prior to therapy and was found to have a clone of 55,XX cells. After treatment leading to a clinical response, the patient relapsed with a clone of 57,XX cells, which were derivatives of the original neoplastic cell line. This is the first case of demonstrated clonal evolution of myeloma in a patient studied prior to chemotherapy. PMID- 4016716 TI - Chromosome analysis of three seminomas. AB - Each of three seminomas revealed chromosome #1 and #12 structural changes in direct preparations and short-term cultures. The #1 changes involved duplication of 1q and loss of 1p; in two, the breakpoint was in the heterochromatic region. The anomaly in #12 was a short arm isochromosome, usually present in duplicate. In one tumor, these were the only structural changes; in the other two, there was also involvement of #7, with extra copies of 7p. In one of these two tumors, a heterochromatic minute was identified after C-banding, and in the other, aside from two different markers containing part of #7, there was a dicentric derived from two chromosomes #15; this tumor proved to be prognostically unfavorable. Three normal chromosomes #1 and XXY sex chromosomes were present in each tumor. Chromosomes #11 and #13 were generally underrepresented, and #12 and #19-22 were over-represented. PMID- 4016717 TI - Increased levels of spontaneous and mutagen-induced chromosome aberrations in skin fibroblasts from patients with adenomatosis of the colon and rectum. AB - Fibroblast cell strains were established from skin biopsies taken from patients with adenomatosis of the colon and rectum (ACR) and their relatives. A total of 57 different strains (33 from patients and 24 from healthy members of ACR families not at an increased risk for colon polyposis) were tested for their frequencies of spontaneous structural chromosome aberrations, i.e., chromatid and isochromatid gaps, breaks, and interchanges. In 47 strains (27 from patients, 20 from controls), the frequencies of structural chromosome aberrations were also determined after exposing the cells to N-methyl-N'-nitro-N-nitroso-guanidine (MNNG). Both spontaneously and after mutagen treatment, the group of patient strains exhibited, on average, approximately twice the number of chromosome aberrations found in the control group. This increase was highly significant (p less than 0.001), even though there was a considerable overlap between patient and control strains. Treatment with MNNG led to a marked increase in chromosome aberrations in both patients and controls. The small differences in aberration frequencies seen between Gardner and other patient strains were clearly insignificant. PMID- 4016718 TI - Spontaneous chromosomal aberrations in patients with precancerous and cancerous lesions of the cervix uteri. AB - Chromosomal aberrations were studied in metaphases from peripheral blood cultures of 52 women with cancer of the cervix uteri, 89 cases of various grades of cervical precancerous lesions, and 47 age-matched normal (control) women. The frequency of metaphases with chromosome and chromatid aberrations was 17.24% in cancer patients, 10.41% in those with precancerous lesions, and 6.39% in control women. There was a significant (p less than 0.001) increase in the frequency of chromosome aberrations in patients with cervical precancerous and cancerous lesions, compared with controls. After the exclusion of the treated cases, cancer patients also revealed a highly significant (p less than 0.001) increase in the frequency of chromosome aberrations, compared with controls. The results of the present study indicate the existence of chromosomal instability in the majority of cervical cancer patients and in some cases of precancerous lesions. The increased frequency of spontaneous chromosome aberrations in patients with precancerous lesions may be of importance for the understanding of their biological behavior. PMID- 4016719 TI - Chromosomal studies in familial polyposis coli. AB - A study of five patients with familial polyposis coli did not demonstrate any structural abnormalities of prometaphase chromosomes from methotrexate synchronized peripheral blood lymphocytes. No chromosomal heritable fragile sites were observed, nor was sister chromatid exchange increased. PMID- 4016720 TI - Effects of noradrenaline on interstitial fluid pressure in induced rat mammary tumours. AB - Interstitial fluid pressure was measured by the wick-in-needle technique in DMBA induced rat mammary tumours during resting conditions and during noradrenaline infusion. The rate of infusion was chosen to increase the systemic blood pressure by 30-40 mmHg, known to result in a markedly increased vascular resistance of these tumours. During resting conditions tumour interstitial fluid pressure was 10.3 +/- 1.3 mmHg (n = 13) but fell to 7.0 +/- 1.1 mmHg (n = 13) during noradrenaline infusion. The results suggests that noradrenaline is likely to affect the pre-capillary resistance vessels of the tumour vascular bed. This result, together with earlier perfusion studies, indicates that noradrenaline is unsuitable for increasing tumour cell perfusion as an adjunctive in radiation and cytotoxic drug therapy. PMID- 4016721 TI - Effect of tumour necrosis factor on growth of Ehrlich ascites tumour cells in vitro and in vivo. AB - Tumour necrosis factor (TNF) suppressed the growth of Ehrlich ascites tumour (EAT) cells in vitro and in vivo. Exposure of EAT cells to TNF for as little as 4 h totally abolished the transplantability of the tumour. At the same time, the rate of glucose uptake and extent of leucine incorporation were significantly reduced. Prolonged treatment with TNF resulted in extensive cell lysis, as determined by trypan blue exclusion and by release of radioactivity from [3H]thymidine-labelled EAT cells. The significance of these observations are discussed. PMID- 4016722 TI - Metabolic studies of 15N-labeled N-nitrosoproline in isolated rat hepatocytes and subcellular fractions. AB - The metabolism of the non-carcinogenic N-nitrosoproline (NPRO) was investigated in vitro using both S9 preparations and isolated hepatocytes from F344 rats. The studies were performed using 15N-labeled nitrosamine and the reaction mixtures were examined mass spectrometrically for the presence of 15N2 or other 15N labeled gaseous products. In addition, the metabolism of NPRO was monitored by capillary gas chromatography. The results indicated no 15N2 production from either the hepatocyte or S9 preparations, as well as no detectable loss of substrate from the reaction mixtures. Mass spectrometric analysis failed to reveal any metabolites of NPRO. The results suggest that NPRO may be refractory to the normal nitrosamine activating enzymes, confirming its suitability for use in human epidemiological studies of endogenous nitrosation. PMID- 4016723 TI - Phase I pharmacologic study of a new Vinca alkaloid: navelbine. AB - Navelbine (NVB) is a new semi-synthetic Vinca alkaloid selected on the basis of its affinity for tubulin. NVB inhibits the polymerisation of tubulin and it has significant antitumor activity on P388 and L1210 leukemias and some other experimental tumors. In the present study, 20 patients (9 carcinomas, 10 lymphomas and 1 blastic crisis of chronic myeloid leukemia) received a median of 4 weekly i.v. doses of NVB. Two patients at least received each dose level: 3.6 mg/m2 (1/10 of the LD10 dose/kg in BDF1 mice), 7.2, 12, 18, 32.4, 35 and 43 mg/m2 per week. A total of 89 doses were administered. All patients had been first heavily pretreated and 17 of them had received a Vinca alkaloid. Leukopenia (neutropenia) was the dose-limiting toxicity. There was no thrombocytopenia. Leukopenia was dose-related and first seen at 32.4 mg/m2 per week. The maximal tolerated dose appears to be about 43 mg/m2. At that dose, 2 out of 3 patients developed severe leukopenia and neutropenia. One localized allergic reaction, one case of transient hepatic dysfunction, and 2 reversible peripheral neuropathies were seen. Pharmacokinetics, studied with a radioimmunoassay (RIA) method, suggested an elimination half-life of 30 h and a plasma clearance of 75 l/h. Four patients with Hodgkin's disease and two patients with non-Hodgkin's lymphoma, all of them refractory to vincristine (VCR) and/or vinblastine (VBL), showed minor responses lasting 2-8 weeks. They had received between 4 and 12 doses of 30 and 43 mg/m2. We recommend for phase 11 trials the dose of 40 mg/m2 per week. PMID- 4016724 TI - Carcinogenicity of N-nitrosobis (2-hydroxypropyl) amine after administration to Syrian hamster skin. AB - Weekly application of N-nitrosobis (2-hydroxypropyl) amine (BHP) at a dose of 50 mg/application to the skin of the neck and flank organ of male Syrian golden hamsters induced no local lesions. However, nearly all treated animals developed internal tumors, primarily of pancreatic, hepatic, respiratory and colorectal origins. Results from this and previous studies indicate that the local carcinogenic effect of nitrosamines depends on the molecular structure of the carcinogen, rather than on tissue specificity. Furthermore, some common types of human cancer could be induced by absorption of specific nitrosamines through skin. PMID- 4016725 TI - Induction of colon cancer in inbred Syrian hamsters by intrarectal administration of benzo[alpha]pyrene, 3-methylcholanthrene and N-methyl-N-nitrosourea. AB - Large bowel neoplasms were induced in male Syrian hamsters of the inbred strain BIO15.16 by intrarectal instillation of benzo[alpha]pyrene (BP), 3 methylcholanthrene (3-MC) or N-methyl-N-nitrosourea (MNU). Groups of hamsters were given 0.8 mg BP once weekly for 30 weeks, 0.8 mg 3-MC twice weekly for 30 weeks, or 0.8 mg MNU once weekly for 15 weeks. The experiment was terminated after 1 year. The incidences of colon neoplasms were 6% with BP exposure, 20% with 3-MC and 95% with MNU. The colon neoplasms induced by BP and 3-MC were mostly adenocarcinomas. In the group given MNU, adenocarcinomas were also produced but a substantial incidence of squamous cell carcinomas was found. These results demonstrate that the colonic mucosa of this strain of hamster is quite susceptible to cancer induction. PMID- 4016726 TI - The non-lethal effects of ionizing radiation and hyperthermia on colony growth in a human bladder cancer cell line. AB - The doses of radiation and 43 degrees C hyperthermia required to produce 90% killing of a human bladder cancer cell line were determined using a classical colony assay. The growth rate of survivors was then described by carrying out colony-size analysis at sequential times after treatment. It was demonstrated that those cells which initially survive radiation frequently show sustained growth delay and that their progeny may stop growing after a few generations of cell division. After an 'equilethal' dose of hyperthermia there is transient growth delay but there is no long term loss of reproductive integrity in the survivors. PMID- 4016727 TI - Retinoyl-phorbol-acetate is a complete skin tumor promoter in SENCAR mice. AB - The semi-synthetic phorbol ester 12-O-retinoyl phorbol 13-acetate (RPA) was tested for activity as a complete tumor promoter, as well as for first or second stage promotion activity, in the skin of SENCAR mice. Unlike in NMRI mice where RPA has been reported to act only as a second stage promoter, in SENCAR mice it has moderate complete promoting activity as well as second stage activity. RPA also induces epidermal hyperplasia and an increase in the number of dark basal keratinocytes. PMID- 4016728 TI - High affinity rosette forming cells in carcinoma of the oral cavity, uterine cervix and breast. AB - Total rosette forming cells (TRFC) and high affinity rosette forming cells (HARFC) were enumerated in 534 patients with carcinoma of oral cavity, uterine cervix or breast, and the results were compared with adult controls. The HARFC levels were found to be significantly decreased in cancer patients, and this decrease was more pronounced in advanced clinical stages. The HARFC levels returned to normal in patients who had a clinical cure but remained low in patients having residual disease. Enumeration of HARFC may therefore be useful in assessing the cell mediated immunity in cancer patients. PMID- 4016729 TI - Mouse strain (STS/A) resistant to mammary tumor induction by hypophysial isografts. AB - Implantation of hypophysial isografts does not lead to induction of mammary tumors in all strains of mice lacking the exogenous murine mammary tumor virus. While O20, C3Hf, and BALB/c females are highly susceptible and C57BL and TSI females are of intermediate susceptibility, the STS females appear to be nearly totally resistant. The resistance of the STS strain is not due to failure of prolactin production by the hypophysial isografts and may therefore be due to a genetically controlled mechanism at target cell level. Neither resistance, i.e., low incidence of mammary tumors (2% in STS), nor susceptibility, i.e., high incidence at low age (93% at 349 days in C3Hf; 83% at 360 days in BALB/c), is dominant. F1 hybrids of strain STS and the two strains C3Hf and BALB/c show high incidences (STS X C3Hf F1, 90%; STS X BALB/c F1, 60%), but the age at which tumors appear (476 and 604 days, respectively) is much higher, suggesting that more than one gene is involved in this type of hormonal carcinogenesis of the mammary gland in mice. PMID- 4016730 TI - Effects of hypoxia, pH, and growth stage on cell killing in Chinese hamster V79 cells in vitro by activated cyclophosphamide. AB - Several factors which influence the sensitivity of Chinese hamster V79 cells to cyclophosphamide (CY) have been studied in vitro in both suspension and monolayer cultures. Activated CY was obtained from the blood of mice 15 to 30 min after i.p. injection of CY (400 mg/kg). At pH 7.4, hypoxia rendered the cells more sensitive to activated CY. At lower values of pH (6.6 and 7.0), there was no difference between the sensitivities of oxic and hypoxic cells, although cells in both conditions were more sensitive to CY than at pH 7.4. Drug sensitivity was markedly affected by the stage of cell growth. Monolayer cultures were most sensitive to CY within a few hours of plating. Cultures then rapidly became less sensitive, with maximum resistance occurring between 24 and 48 h after plating, while the cells were still exhibiting rapid exponential growth. This development of resistance parallelled the formation of small colonies (2 to 4 cells), implying that intercellular contact may confer resistance to killing by activated CY. PMID- 4016731 TI - Direct alkylation of 2'-deoxynucleosides and DNA following in vitro reaction with acrylamide. AB - Reaction of the rodent carcinogen acrylamide (AM) at pH 7.0 and 37 degrees C for 10 and 40 days with 2'-deoxyadenosine (dAdo), 2'-deoxycytidine (dCyd), 2' deoxyguanosine (dGuo), and thymidine (dThd) resulted in the formation of 2 formamidoethyl and 2-carboxyethyl adducts via Michael addition. The alkylated 2' deoxynucleoside adducts isolated (% yield after 40 days) were 1-(2-carboxyethyl) dAdo (1-CE-dAdo) (8%), N6-CE-dAdo (21%) (via Dimroth rearrangement of 1-CE-dAdo), 1-CE-dGuo (4%), 7-(2-formamidoethyl)-Gua (7-FAE-Gua) (6%), 7, 9-bis-FAE-Gua (1%) (formed by reaction of AM with depurinated 7-FAE-Gua during the course of the reaction), and 3-FAE-dThd (4%). The products isolated following in vitro reaction of AM with calf thymus DNA at pH 7.0 and 37 degrees C for 40 days were (nmol/mg DNA) 1-CE-dAdo (5.5), N6-CE-dAdo (1.4), 3-CE-dCyd (2.8), 1-CE-dGuo (0.3), and 7 FAe-Gua (1.6). Compound 3-FAE-dThd was not detected. Structures were assigned on the basis of chemical properties, UV spectra, and electron impact, chemical ionization, desorption chemical ionization, Californium-252 fission fragment ionization, and fast atom bombardment mass spectra. A facile hydrolysis of the amide group to a carboxylic acid was observed when AM alkylated a ring nitrogen adjacent to an exocyclic nitrogen atom. In previous studies, we had observed an analogous phenomenon when studying the in vitro reactions of acrylonitrile with DNA, i.e., a facile hydrolysis of nitrile to carboxylic acid when acrylonitrile alkylated (via Michael addition) a ring nitrogen adjacent to an exocyclic nitrogen. Since the nitrile group hydrolyzes to a carboxylic acid via an amide intermediate, we had hypothesized in the present study that the same facile hydrolysis of amide to carboxylic acid would occur under identical stereochemical conditions as had occurred with the nitrile group. Thus, in vitro alkylation of calf thymus DNA by both acrylonitrile and, in the present study, AM, resulted in mixed adduct formation. PMID- 4016732 TI - Metabolism of benzo(a)pyrene by variant mouse hepatoma cells. AB - Four mouse hepatoma cell lines, a parent (Hepa-1c1c7) and three variants (MUL12, BPrc1, and TAOc1BPrc1) which had been derived from Hepa-1c1c7 by the fluorescence activated cell sorter, were incubated with benzo(a)pyrene, and the metabolites were analyzed by high-pressure liquid chromatography. Among these four cell lines, Hepa-1c1c7 and MUL12 metabolized benzo(a)pyrene the most quickly and to the greatest extent, and BPrc1 had the weakest metabolic activity for this substrate. TAOc1BPrc1 had intermediate benzo(a)pyrene-metabolizing activity, depending on cell density and incubation time. At low cell density, the active variant TAOc1Bprc1 resembled the weakly active Bprc1 in accumulating a low amount of ethyl acetate-soluble metabolites in the medium while, at high cell density, TAOc1Bprc1 resembled the parent clone Hepa-1c1c7 and the highly active variant MUL12. At short incubation times, TAOc1Bprc1 also had low conjugating activity while, at longer incubation times, the conjugating activity approached that of Hepa-1c1c7 and MUL12. At low cell density, Bprc1 was able to produce phenols, but this variant did not seem to have this ability at high cell density. When the substrate concentration was 4 microM and the incubation time was 24 h, beta glucuronidase treatment of water-soluble metabolites released about 5.3 times more pmol of quinones compared with phenols. But when the substrate concentration was 25 nM, beta-glucuronidase released about 2.0 times as many phenols compared with quinones. The parent and the two more actively metabolizing variants showed differences in the peak times of accumulation of 9,10-diol and 7,8-diol of benzo(a)pyrene, which may have implications for binding to DNA and nuclear proteins. It was concluded that BPrc1 has basal but not easily inducible aryl hydrocarbon hydroxylase activity, whereas Hepa-1c1c7, MUL12, and TAOc1Bprc1 have basal and inducible aryl hydrocarbon hydroxylase activity. These results show that variants of a single parent cell line can exhibit significant differences in the rate and extent of metabolism of benzo(a)pyrene. PMID- 4016733 TI - Migration of tumor cells to organ-derived chemoattractants. AB - Certain tissues contain unique factors which are chemotactic for metastatic tumor cell lines. Extracts of bone, brain, liver, and lung were tested for their ability to promote either the migration or the chemoinvasion, i.e., their penetration through a reconstituted basement membrane barrier, of various metastatic tumor cells. Using a modified Boyden chamber assay for chemotaxis, B16 Br2 melanoma cells, which metastasize to brain, migrated most actively to brain extract. Lung-directed T241-PM2 fibrosarcoma cells migrated selectively to lung extract. Further, murine M50-76 reticulum cell sarcoma cells, which metastasize to liver and ovaries, were preferentially attracted to liver extract, and MCF-7 breast adenocarcinoma cells with high bone and brain colonization potential were found to migrate most actively to bone and brain extracts. Partial purification of tissue extracts showed that the factors in brain and liver are of different molecular weights. These data suggest that tissue-specific factors in different target tissues attract tumor cells which home to those sites. PMID- 4016734 TI - Cell surface effects of adriamycin and carminomycin immobilized on cross-linked polyvinyl alcohol. AB - Previous reports have claimed Adriamycin to be cytotoxic to cultured tumor cells when the drug is covalently immobilized on a solid support, thus suggesting a cell surface mechanism of action for the drug. Although these previous reports attempted to rule out released drug or endocytosis of drug-support particles as alternative explanations for the observed cytotoxicity, a more thorough analysis is necessary to substantiate fully the cell surface idea. In the present work, the stability of the drug-support linkage was increased by use of cross-linked polyvinyl alcohol as the support and cyanuric chloride or a diazonium salt for attachment of the drug. Different anthracycline orientations were tested by coupling Adriamycin at the amino sugar and carminomycin at the D-ring. The Adriamycin cross-linked polyvinyl alcohol and carminomycin cross-linked polyvinyl alcohol preparations had much lower drug release rates than did the earlier used carbamate-linked Adriamycin cross-linked agarose materials. All three immobilized drug preparations inhibited the growth of L1210 or S180 clones following 2- or 20 h incubation with cells at 37 degrees C. The results strongly support the concept that immobilized anthracyclines can be cytotoxic to cultured cells, for at least two different orientations of the drug on the support. PMID- 4016735 TI - Rational selection of adjuvant chemotherapy after cytoreduction surgery for murine neuroblastoma. AB - Improving the prognosis of advanced neuroblastoma remains an important yet unachieved goal of pediatric oncology, a fact which may be related to an insufficient analysis of the role played by cytoreductive surgery. Utilizing strain A mice bearing C-1300 syngeneic neuroblastoma, tumor biology and host immunocompetence were studied after cytoreduction surgery and adjuvant chemotherapy. Cell kinetic analysis in the residual tumor demonstrated an increase of the proliferative fraction 18 to 42 h after operation, but the same peak proliferation was delayed in bone marrow cells to 24 to 96 h. The potential for drug distribution to the tumor after cytoreduction surgery was assessed by injecting Na251CrO4 and measuring tumor uptake. There were two significant (P less than 0.05) peaks of activity at 6 h and 3 days, suggesting local edema and neovascularity, respectively. Injection of both cell cycle specific and nonspecific adjuvant chemotherapeutic agents in a dosage of one-fourth of their 50% lethal dose at 24 or 72 h following surgical cytoreduction did not induce any antitumor activity at either injection time. However, when cyclophosphamide was given in this dose, the C-1300 tumor growth was impaired, an effect which was largely abrogated by first subjecting the tumor bearer to thymectomy and irradiation. The transfer of spleen cells from adjuvant cyclophosphamide-treated mice to tumor-inoculated normal mice significantly delayed tumor appearance when comparison was made with animals treated by operation alone, and such recipients also exhibited a more prolonged survival. These data suggest that the antitumor activity of cyclophosphamide following cytoreduction surgery of C-1300 neuroblastoma is mediated by both pharmacological and immunological mechanisms. PMID- 4016736 TI - Effects of cimetidine, nitrite, cimetidine plus nitrite, and nitrosocimetidine on tumors in mice following transplacental plus chronic lifetime exposure. AB - Cimetidine (CM), a drug widely prescribed for ulcers, readily undergoes nitrosation to form nitrosocimetidine (NCM), a genotoxic agent. In a test of the chronic effects of NCM in mice, (C57BL/6 X BALB/c)F1 mice were exposed chronically to NCM (113 or 1130 ppm) in the drinking water from preconception through prenatal and neonatal development and adult life. Each group consisted of 40 to 80 mice of each sex, and median survival time was 27 months. Other groups were given CM alone or in combination with NaNO2 (184 or 1840 ppm), or NaNO2 alone. None of the chemical treatments had large effects on reproductive parameters, survival, or incidence of nonneoplastic lesions. CM treatment was associated with a small but significant increase in incidence of lymphomas in females, 41 of 59 (69%), compared with 31 of 66 controls (47%, P = 0.01). No females receiving either dose of NCM developed mammary carcinomas (0 of 91), compared with an incidence of four of 66 controls (6%, P = 0.03). Males given the high-dose combination of CM and NaNO2 showed a higher incidence of lung tumor bearers than controls (71 of 79 versus 30 of 52, P less than 0.01) and also experienced a significant, dose-dependent increase in numbers of large lung tumors (greater than 1 cm in diameter), lung carcinoma, and metastatic lung tumors. Females given the higher dose of NCM had significantly greater incidence of mice with large lung tumors than controls (nine of 41 versus three of 66, P = 0.009). The possibility of carcinogenicity of cimetidine, nitrosocimetidine, and cimetidine plus nitrite is discussed. PMID- 4016737 TI - Inhibition of the mutagenicity of aromatic amines by the plant flavonoid (+) catechin. AB - Addition of the plant phenolic flavonoid (+)-catechin to rat liver microsomes inhibited the mutagenicity of the aromatic amines 2-aminofluorene and 4 aminobiphenyl in the Ames test. Similarly, (+)-catechin decreased the mutagenicity of N-hydroxy-4-amino-biphenyl, the proximate carcinogen, but, in contrast, had no effect on the mutagenicity of other direct-acting carcinogens such as N-methyl-N'-nitro-N-nitrosoguanidine and 9-aminoacridine. In vitro addition of (+)-catechin gave rise to a dose-dependent inhibition of the cytochrome P-450-dependent benzphetamine N-demethylase and ethoxyresorufin O deethylase activities. This was achieved by impairment of the electron flow from the reduced pyridine nucleotide to the cytochrome. However, administration of (+) catechin to rats had no effect on the in vitro mixed-function oxidase activities. It is concluded that the (+)-catechin inhibits the mutagenicity of aromatic amines in the Ames test by interfering with their cytochrome P-450-dependent bioactivation and by direct interaction with the proximate carcinogen, but the former mechanism is unlikely to occur in vivo because the high doses of the flavonoid required are not achieved. PMID- 4016738 TI - Metabolic oxidation of carcinogenic arylamines by rat, dog, and human hepatic microsomes and by purified flavin-containing and cytochrome P-450 monooxygenases. AB - Hepatic N-oxidation and aryl ring oxidation are generally regarded as critical activation and detoxification pathways for arylamine carcinogenesis. In this study, we examined the in vitro hepatic metabolism of the carcinogens, 2 aminofluorene (2-AF) and 2-naphthylamine (2-NA), and the suspected carcinogen, 1 naphthylamine (1-NA), using high-pressure liquid chromatography. Hepatic microsomes from rats, dogs, and humans were shown to catalyze the N-oxidation of 2-AF and of 2-NA, but not of 1-NA; and the rates of 2-AF N-oxidation were 2- to 3 fold greater than the rates of 2-NA N-oxidation. In each species, rates of 1 hydroxylation of 2-NA and 2-hydroxylation of 1-NA were comparable and were 2- to 5-fold greater than 6-hydroxylation of 2-NA or 5- and 7-hydroxylation of 2-AF. Purified rat hepatic monooxygenases, cytochromes P-450UT-A, P-450UT-H, P-450PB-B, P-450PB-D, P-450BNF-B, and P-450ISF/BNF-G but not P-450PB-C or P-450PB/PCN-E, catalyzed several ring oxidations as well as the N-oxidation of 2-AF. Cytochromes P-450PB-B, P-450BNF-B, and P-450ISF/BNF-G were most active; however, only cytochrome P-450ISF/BNF-G, the isosafrole-induced isozyme, catalyzed the N oxidation of 2-NA. The purified porcine hepatic flavin-containing monooxygenase, which was known to carry out the N-oxidation of 2-AF, was found to catalyze only ring oxidation of 1-NA and 2-NA. No activity for 1-NA N-oxidation was found with any of the purified enzymes. These data support the hypothesis that 1-NA is probably not carcinogenic. Furthermore, carcinogenic arylamines appear to be metabolized similarly in humans and experimental animals and perhaps selectively by a specific form of hepatic cytochrome P-450. Enzyme mechanisms accounting for the observed product distributions were evaluated by Huckel molecular orbital calculations on neutral, free radical, and cation intermediates. A reaction pathway is proposed that involves two consecutive one-electron oxidations to form a paired substrate cation-enzyme hydroxyl anion intermediate that collapses to ring and N-hydroxy products. PMID- 4016739 TI - Major urinary metabolites in hamsters and rats treated with N-nitroso(2 hydroxypropyl)(2-oxopropyl)amine. AB - Rats and hamsters were administered a single dose of N-[1-14C]nitroso(2 hydroxypropyl)(2-oxopropyl)amine (HPOP), and their urinary metabolites were examined at various time intervals. In both species, urinary excretion of radiolabeled metabolites reached a plateau at 6 h following injection. At this time, 35 and 28% of the total dose was found in the urine of rats and hamsters, respectively. Separation by liquid chromatography and subsequent characterization by nuclear magnetic resonance, gas chromatography-mass spectroscopy, and infrared showed that the major metabolites in rat urine were HPOP, N-nitrosobis(2 hydroxypropyl)amine (BHP), and their glucuronic acid conjugates. The conjugates accounted for 30 and 9%, while free HPOP and BHP accounted for 42 and 16% of the total metabolites, respectively. Hamster urine, on the other hand, contained free HPOP, BHP, their glucuronic acid conjugates, and a sulfate ester of HPOP not found in rat urine. Six h following administration of HPOP, hamster urine contained BHP, BHP glucuronide, HPOP, HPOP glucuronide, and HPOP sulfate ester at levels of 35, 9, 16, 9, and 14%, respectively. These data suggest that hamsters reduce HPOP to BHP more efficiently than rats, while rats are more effective in forming their glucuronic acid conjugates. Hamsters differ significantly from rats in their capacity to form and excrete the sulfate ester of HPOP. PMID- 4016740 TI - Temperature effect on mitoxantrone cytotoxicity in Chinese hamster cells in vitro. AB - The effect of heat on 1,4-dihydroxy-5,8-bis[2-[(2-hydroxyethyl)amino]ethylamino] 9, 10-anthracenedione dihydrochloride (DHAD; mitoxantrone, NSC 301739) cytotoxicity was studied in V79 Chinese hamster cells. An overnight exposure to the drug at 40 degrees C enhanced drug damage in chromosome aberrations, culture growth, and cellular reproductive integrity. Preincubation of cells overnight in medium containing no drug at this temperature also showed some enhancement in subsequent DHAD lethality (at 37 degrees C as well as 43 degrees C). Short exposures (1 h) to DHAD at 43 degrees C was more damaging than were exposures at 37 degrees C. This was also true for cells in the plateau phase of culture growth. As compared with exponentially growing cells, plateau-phase cells were more resistant to DHAD. PMID- 4016741 TI - Mechanism of synergy between N-phosphonacetyl-L-aspartate and dipyridamole in a human ovarian carcinoma cell line. AB - Previous results from our laboratory have shown that the nucleoside transport inhibitor dipyridamole (DP) markedly augmented both the in vitro and in vivo activities of the pyrimidine antimetabolite N-phosphonacetyl-L-aspartate (PALA). In a human ovarian carcinoma cell line (2008), DP increased the activity of PALA by 1 to 2 logs in growth rate and clonogenic assays while exhibiting no cytotoxicity of its own. The concentration of DP used (1 microM) in these assays resulted in over 80% reduction in uridine uptake in the 2008 cells at the end of 1 h. The activity of PALA and PALA plus DP was completely antagonized by the addition of exogenous uridine in a dose-dependent manner. Addition of other nucleosides to concentrations as high as 1000 microM failed to rescue the ovarian cells from the drug combination, and combining two nucleosides together did not antagonize PALA and PALA plus DP activity to any greater extent. Cellular nucleotide pool analysis by anion-exchange high-performance liquid chromatography revealed that dipyridamole further reduced the already depressed uridine triphosphate and cytidine triphosphate pools of cells exposed to PALA, while the guanosine triphosphate pool was slightly elevated. Uridine supplementation resulted in partial replenishment of the uridine triphosphate and cytidine triphosphate pools, but the absolute levels remained below control values. The acute drug-induced changes in nucleotide pools in 2008 xenografts growing in athymic mice paralleled those observed in vitro. Evidence presented here supports the ability of DP to potentiate PALA activity against a human ovarian carcinoma cell line. The mechanism of synergy relates to the inhibition of pyrimidine salvage in the tumor cells via the blockade of uridine uptake. PMID- 4016742 TI - Microcirculation of hepatic nodules from diethylnitrosamine-treated rats. AB - The microcirculation of nodules (0.5 to 10 mm in diameter) from diethylnitrosamine-treated rats was studied in perfused livers. Microlight guides were placed on nodules and surrounding tissue on the capsular surface of the liver to measure fluorescence due to fluorescein-dextran (12 microM), a dye confined to the vascular space, infused via the hepatic artery and portal vein separately or simultaneously. The fluorescence increase due to fluorescein dextran infusion via the artery and vein simultaneously was used to compare vascular space in nodules with that of surrounding tissue. The vascular space of nodules less than 1 mm in diameter was only about one-half as large as that of surrounding tissue. In contrast, in nodules 1 to 2 mm in diameter, the vascular space was similar to values from surrounding tissue. This was largely due to an increase in the fluid entering via the artery. As nodules grew from 2 to 10 mm in diameter, the vascular space decreased as a function of nodule size to 40% of surrounding tissue. The sum of fluorescence increases due to fluorescein-dextran infused via the artery and vein separately always equalled values obtained from simultaneous infusions. From these measurements, the fraction of vascular fluid observed by the microlight guide that entered the liver via the artery was calculated. In tissue surrounding nodules, fluid entering from the artery was 19% of the total, a value approximating the fraction of fluid pumped into the liver via the artery (25%). The percentage of fluid in the nodule that entered the liver via the hepatic artery increased progressively to 100% of the total as nodules grew from 2 to 10 mm in diameter. Thus, nodules become increasingly dependent on the hepatic artery and less dependent on blood supply via the portal vein as they grow. PMID- 4016743 TI - Effect of diethylstilbestrol on the frequencies of sister chromatid exchange in vitro and in vivo. AB - The influence of diethylstilbestrol (DES) on the SCE frequency was studied in various cell systems (V79, HTC, DON, WI-38, human lymphocytes) differing in their ability to metabolize the two promutagens benzo(a)pyrene and cyclophosphamide as well as after incubation with exogenous metabolic systems (S9 mix and peroxidase/H2O2) and in vivo on cells from the bone marrow of the Chinese hamster. DES concentrations from 10(-6) to 10(-4) M were tested. Slight SCE induction was observed only at the highest concentration (10(-4) M) of DES in human lymphocytes treated with DES for the entire culture period of 72 h and in DON cells. No increase of the SCE rate was determined in the other cell lines and in vivo. The combination with S9 mix or peroxidase/H2O2 also had no influence on the SCE frequency. These findings cast doubt on the assumption that DES is metabolized to a DNA-damaging compound subsequently leading to SCE induction. The positive findings in the SCE test are more likely to be products of an indirect and rather unspecific effect. PMID- 4016744 TI - Effects of organoselenium compounds on induction of mouse forestomach tumors by benzo(a)pyrene. AB - The selenium analogues of three known inhibitors of chemical carcinogenesis were synthesized and the compounds were tested for their ability to inhibit the induction of forestomach tumors in mice by benzo(a)pyrene. Groups of female CD-1 mice were given NIH-07 diet, or NIH-07 diet to which one of the following test compounds had been added: p-methoxyphenol (30 mumol/g diet and 3.3 mumol/g diet); p-methoxybenzeneselenol (3.3 mumol/g diet); benzylthiocyanate (0.045 mumol/g diet); benzylselenocyanate (0.045 mumol/g diet); phenothiazine (3.8 mumol/g diet); and phenoselenazine (3.8 mumol/g diet). The test compounds were administered for 1 week prior to treatment with benzo(a)pyrene, during the 4 weeks of benzo(a)pyrene treatment, and for 1 week after benzo(a)pyrene treatment. Twelve weeks later the mice were sacrificed and forestomach tumors were counted and confirmed histologically as papillomas. p-Methoxyphenol was the most effective inhibitor and was the only one which significantly reduced both the percentage of tumor-bearing animals and the number of forestomach tumors per animal. At the 3.3-mumol/g diet, p-methoxyphenol reduced the number of tumors per animal from 3.3 to 0.8 (P less than 0.0003). p-Methoxybenzeneselenol reduced the number of tumors per animal from 3.3 to 2.0 (P less than 0.05). Benzylthiocyanate showed no significant inhibitory effect, but benzylselenocyanate reduced the number of tumors per animal from 3.3 to 1.7 (P less than 0.01). Phenothiazine significantly enhanced the number of tumors per animal from 3.3 to 6.5 (P less than 0.004). Phenoselenazine had no effect on tumor induction. The results of this study indicate that two synthetic organoselenium compounds, p methoxybenzeneselenol and benzylselenocyanate, are effective inhibitors of mouse forestomach tumorigenesis induced by benzo(a)pyrene. PMID- 4016745 TI - Comparative properties of five human ovarian adenocarcinoma cell lines. AB - We describe the derivation of three human ovarian carcinoma cell lines and the comparison of their properties with two previously described cell lines of like histology (SKOV-3 and CAOV-3). Two of the new lines (HOC-1 and HOC-7) were derived from separate ascites tumors (at 9-month intervals) of a patient with well-differentiated serous adenocarcinoma of the ovary. The third new line, HEY, was derived from a human ovarian cancer xenograft (HX-62) originally grown from a peritoneal deposit of a patient with moderately differentiated papillary cystadenocarcinoma of the ovary. The cell lines demonstrated differential ability to grow in semisolid culture and as xenografts in immunologically deprived CBA/CJ mice. Dose-response curves were generated for clonogenic cell survival of cells exposed to common chemotherapeutic agents; one of the lines (HEY) shows a degree of resistance to the alkylating agent cis-diamminedichloroplatinum(II) (cis platinum). Common karyological features included structural abnormalities of chromosomes 3 and 11. Heterogeneity of expression of ovarian tumor-associated antigens was documented. PMID- 4016746 TI - Monoclonal antibodies against a component related to soluble estrogen receptor. AB - Mice were immunized with 1 to 3 micrograms of cytoplasmic estrogen receptor fragment purified from human myometrium by affinity chromatography. Two RE antibody-secreting clones were detected from one fusion that were capable of precipitating cytosol RE. Monoclonal antibody D5 (subclass IgG1) reacts with an antigen that is related to RE from immunoprecipitation studies but which can be separated from the hormone binding unit. In the presence of anti-mouse serum, D5 precipitates labeled human cytoplasmic RE complexes from breast tumor, fibroid, myometrial, and endometrial preparations but does not react with nuclear RE from human endometrium or cytoplasmic RE from other species tested. Conversely, antibody C3 (Class IgM) precipitates human cytoplasmic RE and nuclear RE complexes as well as labeled cytoplasmic RE from rat and calf uterus and chick oviduct. Neither antibody reacts with progesterone receptor or androgen receptor from human breast tumor, SHBG from human plasma, or rat alpha-fetoprotein. With D5, steroid labeling of cytoplasmic RE at 25 degrees increased the RE immune complex precipitated. D5 precipitates molybdate-stabilized RE from myometrial cytosol when labeled at 25 degrees but not at 4 degrees. C5 precipitates molybdate-stabilized RE whether cytosol was steroid-labeled at 4 degrees or 25 degrees. For D5, optimal precipitation of RE from human breast tumor was observed when cytosol was steroid-labeled at 25 degrees in buffers of pH range 5 to 6. Immunochemical studies indicate that D5 is associated with a Mr 29,000 component in RE-positive cytosols. Electrofocusing and sucrose density gradient analysis confirmed that D5 antigen is a non-hormone-binding component related to cytosolic RE from breast tumor and myometrium. PMID- 4016747 TI - Immunoradiometric studies with monoclonal antibody against a component related to human estrogen receptor. AB - A human specific monoclonal antibody (D5) raised against a Mr 36,000 cytosolic estrogen receptor component (RE) partially purified from human myometrium was used to develop a simple, rapid, and sensitive solid-phase immunoradiometric assay (IRMA) for the reactive antigen in tissue cytosols from breast tumors, myometrium, endometrium, and endometrial carcinomas. The IRMA did not detect antigen in RE-negative cytosols from human breast tumors and endometrial carcinomas. RE-positive cytosols from chick oviduct and calf and rat uteri failed to produce an IRMA response. A pilot study indicated a significant correlation (P less than 0.001) between D5 IRMA value and RE sites in breast tumors assayed by [3H]estradiol binding sites. The presence of D5 antigen was dependent on the presence of cytosolic RE but not progesterone receptor. RE-positive patients age 50 years and over demonstrated significantly higher D5 assay values than did patients under 50 years. The data suggest that the D5 antigen is a component of the estrogen receptor or coordinately regulated with the receptor in human cells and that the assay method may have clinical use. PMID- 4016748 TI - Location and distribution of difucoganglioside (VI3NeuAcV3III3Fuc2nLc6) in normal and tumor tissues defined by its monoclonal antibody FH6. AB - The distribution of a novel difucoganglioside (6B ganglioside, NeuAc alpha 2--- 3Gal beta 1----4[Fuc alpha 1----3]GlcNAc beta 1----3Gal beta 1----4[Fuc alpha 1-- -3]GlcNAc beta 1----3Gal beta 1----4Glc beta 1----1Cer) in various normal adult and fetal tissues, as well as in cancer tissues, has been studied by immunoperoxidase staining with a specific monoclonal antibody, FH6, directed to this antigen. A large variety of embryonic and fetal tissues (stomach, colon, small intestine, pancreas, esophagus, lung, and heart) showed a diffuse, weakly positive staining, particularly in the epithelial layer, up to the 70th to 80th day of gestation. However, no staining was observed in various normal adult tissues, including gastrointestinal and glandular epithelial tissues which were stained positively by antibody N-19-9 (directed to sialyl-Lea) or CSLEXI (directed to sialyl-Lex). FH6-positive loci were limited to the proximal convoluted tubuli in kidney and granulocytes. In contrast, 44 of 76 cases of cancer tissue tested, including gastric, colonic, lung, breast, and renal cancers, showed clearly positive staining. The intensity of staining in gastric and colonic cancer tissues by FH6 antibody was weaker and less frequent, although the incidence of positive staining for lung (50%) and breast cancer (86%) was significantly higher than that of the antigen stained by monoclonal antibody FH4 (Y. Fukushi, S. Hakomori, and T. Shepard, J. Exp. Med., 159: 506-520, 1984), which is directed to the asialo core of the FH6 antigen. The antigen levels in the serum of patients with various cancers, inflammatory diseases, and normal subjects were determined by radioimmunoassay. The antigen level was found to be significantly higher in the serum of some patients with cancer, particularly lung, liver, and pancreatic cancers, as compared with the serum levels in other types of cancer, noncancerous diseases, and normal subjects. PMID- 4016749 TI - Photodynamic therapy of intraocular tumors: examination of hematoporphyrin derivative distribution and long-term damage in rabbit ocular tissue. AB - Studies were performed to determine the distribution of hematoporphyrin derivative (HPD) in ocular structures and to characterize long-term damage associated with ocular HPD photodynamic therapy. Pigmented rabbits with an amelanotic melanoma heterotransplanted to the iris were used to obtain quantitative tissue levels of HPD as well as to document HPD localization by fluorescence microscopy. HPD was administered i.v., and tissue concentrations of HPD were determined by spectrofluorometry following porphyrin extraction. Vascular structures such as the tumor, iris, and choroid-retina as well as the aqueous fluid from eyes containing tumors demonstrated rapid HPD localization. The sclera had minimal HPD uptake, and the drug was not detected in avascular structures such as the lens or cornea. HPD was cleared from all ocular structures except the tumor and choroid-retina by 24 h following injection. Fluorescence microscopy data indicate that HPD remained in the avascular photoreceptor cell outer segments of the retina. Long-term damage was documented in rabbits which received HPD photodynamic therapy to a 1-sq cm area of retina via transpupillary light delivery. Acute damage to the exposed area of retina (in the form of a chorioretinal scar) could be induced. This damage was permanent but not progressive. Lens opacities were not observed, and the cornea, aqueous, and vitreous remained clear on all test eyes. The results from these studies suggest that HPD photodynamic therapy may provide a selective and safe approach to the treatment of ocular tumors. PMID- 4016751 TI - Dome formation by a human colonic adenocarcinoma cell line (HCA-7). AB - A new cell line, HCA-7, has been established from a primary human colonic adenocarcinoma. The HCA-7 cells have an epithelial morphology by phase-contrast microscopy, they secrete carcinoembryonic antigen, and they form adenocarcinomas when injected s.c. into nude mice. HCA-7 cells retain some of the morphological and functional polarity exhibited by normal colonic epithelium. Cells form a polarized epithelial sheet when grown on tissue culture plastic in standard culture medium (Dulbecco's modification of Eagle's medium with 10% fetal calf serum). The cells were shown to be structurally polarized with sparse microvilli present at the apical surface but absent from the basolateral surface. Cells were connected by apical tight junctions and frequent desmosomes. Confluent monolayers of HCA-7 cells formed "domes" or "hemicysts" due to vectorial fluid transport resulting in fluid accumulation in localized areas of the monolayer. HCA-7 cells will provide a useful system for studying the role of hormones and other factors in the control of transepithelial transport and maintenance of cell polarity. PMID- 4016750 TI - Effects of structural modifications of antitumor antibiotics (luzopeptins) on the interactions with deoxyribonucleic acid. AB - Luzopeptins consist of two identical, substituted quinolines linked to a cyclic decadepsipeptide, with a 2-fold symmetry. Luzopeptin A, with two acetylated sites in its peptide ring, is active against several experimental animal tumor systems. Luzopeptin B (one acetylated site) is less active, and luzopeptin C (no acetylation) is inactive. Our studies showed that all three luzopeptins and a half-molecule of luzopeptin C exhibited similar fluorescence (400 to 700 nm, with a peak at 490 to 496 nm) with an excitation spectrum in the 200 to 450 nm range (with a peak at 250 to 252, 337, and 385 nm). The half-molecule had the strongest fluorescence, followed in order by luzopeptins A, B, and C. DNA binding quenched both fluorescence and absorption of luzopeptins. Studies of the DNA-induced fluorescence and absorption quenching and the drug-induced viscosity and gel electrophoretic mobility changes of DNA suggested that luzopeptin C was slightly more effective than luzopeptins B and A in both the bifunctional DNA intercalation and the drug-induced DNA-DNA intermolecular cross-linking. Thus, the lack of antitumor activity of luzopeptin C is not the result of the lack of interactions with DNA. The half-molecule of luzopeptin C (quinoline with a pentapeptide) and smaller fragments (quinoline alone or with one to four peptide residues) did not react with DNA. Thus, the planar quinoline chromophore alone is unable to intercalate with DNA. The peptidic cyclic structure of luzopeptins is essential for the bifunctional intercalation of the twin chromophores, probably by providing proper conformational orientations of the chromophores. PMID- 4016752 TI - Induction of heat shock protein synthesis in murine tumors during the development of thermotolerance. AB - The function of one or more heat shock proteins (HSPs) may be to confer protection of cells against thermal damage. We examined the induction kinetics of thermotolerance and the synthesis of HSPs in murine tumor models. Squamous cell carcinomas (SCC VII/SF) or radiation-induced fibrosarcomas (RIF) were implanted in the flanks of C3H mice. These flank tumors were first exposed to an elevated temperature (41 degrees-45 degrees C) for a fixed duration, for example, 43 degrees C for 15 min. Some of the tumors were excised immediately, and tumor cell suspensions were made. The other mice with tumors were returned to the cages and left undisturbed for various times up to 72 h before being sacrificed. Again, tumors were then removed and tumor cell suspensions were prepared. These tumor cells were either challenged with a second heat treatment at 45 degrees C in vitro or labeled with [35S]methionine at 37 degrees C in vitro. The tumor cell survival after the combined heat treatments was measured using the in vitro cloning assay. The cellular proteins were analyzed by one- or two-dimensional gel electrophoresis. We found that mild heat shock induced thermotolerance in murine tumors, a result consistent with those of others. The kinetics of induction and decay of thermotolerance depended on the temperature and duration of the priming treatment. Mild heat shock also enhanced the rate of synthesis and accumulation of some HSPs during the development of thermotolerance. For example, after an initial treatment at 43 degrees C for 15 min, the rates of synthesis of HSPs with molecular weights 68,000, 70,000, and 88,000 were greatly enhanced in SCC VII/SF tumors when compared to unheated controls. Qualitatively similar results were seen with radiation-induced fibrosarcoma tumors. The rate of synthesis of Mr 68,000 to 70,000 HSPs reached maximum value (300% of control value) 2 to 4 h after heat shock and decreased to the control value 6 to 24 h later. On the other hand, the rate of synthesis of actin, a major structural cellular protein, remained relatively constant throughout the 72 h of experiments. We then determined the relationship between the synthesis and accumulation of these HSPs and the expression of thermotolerance in murine tumors after a priming heat treatment. The data indicate that the levels of Mr 68,000 to 70,000 HSPs correlate well with thermotolerance.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 4016753 TI - Hepatocyte surface molecule involved in the adhesion of TA3 mammary carcinoma cells to rat hepatocyte cultures. AB - To identify adhesion molecules involved in the formation of liver metastases, we prepared monoclonal antibodies against rat liver plasma membranes, that inhibited the adhesion of mouse metastatic TA3 mammary carcinoma cells to rat hepatocytes in vitro. Two such antibodies (designated OPAR-1 and OPAR-2) were obtained, that inhibited by over 70%. As assessed with gel electrophoresis and immunoblotting, these antibodies bound predominantly to plasma membrane proteins with molecular weights of 125,000 and 100,000. Using immunoelectron microscopy, the OPAR antigen was found to be abundantly present on the sinusoidal surface of hepatocytes, and in addition on contiguous hepatocyte surfaces and Kupffer cells, but was absent from sinusoidal endothelial cells. The tissue distribution and molecular weight indicate that the OPAR antigen is different from other hepatic adhesion molecules. Adhesion of MB6A lymphosarcoma cells was not inhibited by OPAR antibodies, indicating that these cells adhere to hepatocytes via a different surface molecule. PMID- 4016754 TI - Thermotolerance and profile of protein synthesis in murine bone marrow cells after heat shock. AB - In this study, we first investigated the survival of colony-forming units, granulocyte and macrophage (CFU-GM), after a single heat treatment. We then examined the induction, development, and decay of thermotolerance in CFU-GM. Finally, we analyzed the profiles of protein synthesis in the total murine bone marrow population during the development of thermotolerance. Several salient features emerged from our study: (a) granulocyte-macrophage progenitors were very sensitive to heat as compared to other mammalian cell lines; (b) CFU-GM can develop thermotolerance after both prolonged heating at 41-42 degrees C or an acute heat treatment at 43 degrees C in vitro; (c) thermotolerance in CFU-GM can be induced in vivo; the kinetics of development of thermotolerance in vivo is similar to that in vitro; (d) in contrast to other cell lines where thermotolerance lasts for several days, tolerance acquired by CFU-GM disappeared within 24 h, regardless of the temperature or duration of the initial heat treatment. The difference between the kinetics of systemic thermotolerance and thermotolerance in CFU-GM in the same animal model shows that bone marrow stem cells, or at least CFU-GM, are not the critical targets for systemic thermal death. When protein synthesis profiles of the heat-shocked bone marrow cells were compared to those from nonheated controls by one- and two-dimensional gel electrophoresis, the rates of synthesis of the Mr 70,000 and 87,000 proteins were shown to be enhanced during the development of thermotolerance. The enhanced rate of synthesis of these polypeptides lasted only 2-4 h and then returned to the control value. PMID- 4016755 TI - Effect of 3-methylcholanthrene on the development of aortic lesions in mice. AB - The effect of a carcinogen, 3-methylcholanthrene (3-MC), on the formation and growth of atherosclerotic lesions in mice was examined. Increasing doses of 3-MC from 15 to 1500 micrograms/kg increased the number and size of lipid-staining lesions in the aorta of AKXL-38a mice that were fed an atherogenic diet for 8 weeks. The number of lesions per mouse was 0.85 +/- 0.19 (SE) for animals treated with 3-MC (150 micrograms/kg) compared to 0.10 +/- 0.10 lesions/mouse for animals given solvent rather than 3-MC. The progression of lesions over time from 5 to 18 weeks showed that 3-MC-treated mice also differed from controls in the size of lesions. The total score per mouse at 18 weeks of atherogenic diet, based on the number of lesions and the size of each lesion, indicated by a score of 1 to 4, was 4.31 +/- 0.71 for 3-MC-treated animals and 2.67 +/- 0.74 for animals given solvent. The effect of 3-MC treatment could be observed at 18 weeks even though the entire dose of 3-MC was given during the first week on the atherogenic diet. These experiments do not distinguish whether 3-MC affects atherosclerotic lesions by acting as a mutagen or by some other mechanism. The composition of an atherogenic diet that produces lesions in mice without high mortality is given as well as a comparison of different methods of evaluating lesion formation. PMID- 4016756 TI - Antimicrotubule effects of estramustine, an antiprostatic tumor drug. AB - Estramustine [17 beta-estradiol 3 N bis(2-chloroethyl)carbamate; EM] is a stable conjugate of estradiol and nor-nitrogen mustard that is used for the treatment of human prostatic carcinoma. We have studied the cytotoxic effects of EM on the cytoskeletal organization of squirrelfish pigment cells (erythrophores) and human prostatic tumor cells (DU 145) in culture. Light and whole-mount electron microscopy studies reveal that, at microM levels (60 to 120 microM), EM has a dose-dependent disruptive effect on cell shape, cytoskeletal organization, and intracellular transport. Upon removal of the drug, the cytological effects of EM are rapidly reversible in fish cells but not DU 145s. Immunofluorescent studies reveal that EM produces microtubule disassembly in fish erythrophores and DU 145 cells. A concomitant disruption of actin-microfilament arrays also occurs in DU 145 cells. These morphological data suggest that EM, in contradistinction to its constituent estradiol: nitrogen mustard species, induces cytotoxicity as an antimicrotubule drug. The observed disruption of the microtubules and cytomatrix of interphase cells is not reversible in the prostatic carcinoma cells. The disruptive action of EM on the cytoskeleton could ultimately produce a cytotoxic antimitotic effect in dividing cells. PMID- 4016757 TI - Differential effects of ellipticine and aza-analogue derivatives on cell cycle progression and survival of BALB/c 3T3 cells released from serum starvation or thymidine double block. AB - 10-[Diethylaminopropylamino]-6-methyl-5H-pyrido[3',4':4,5] pyrrolo[2,3 g]isoquinoline (BD-40) (NSC-327471D) is an aza-ellipticine derivative with a promising antitumor activity (M. Marty, C. Jasmin, P. Pouillard, C. Gisselbrecht, G. Gouvenia, and H. Magdalainat, 17th Annual Meeting of the American Society of Clinical Oncology, C-108, 1981) and less toxicity than ellipticine. We have compared the effects of ellipticine, several of its analogues, and two aza analogue ellipticine derivatives (BD-40 and BR-1376) on cell cycle progression of BALB/c 3T3 mouse cells under different growth conditions. Both drug series were found to stop cell growth and block cells in G2 phase in exponentially growing cultures and cultures released from a thymidine double block. Long-term viability of these cells was completely suppressed after a short exposure to the drugs. In contrast, while ellipticine and its derivatives caused identical effects in cells recovering from serum starvation, BD-40 and BR-1376 did not block cells in G2 phase and did not prevent the completion of the first division round occurring after serum addition to quiescent cells. This transient refractory state was accompanied by a total conservation of long-term viability of these cells at least for the next 6 h following serum and drug addition. This lack of effect was not related to an impaired drug uptake by cells recovering from serum starvation or by a dramatic change in drug distribution inside the cells. These results indicate that the nitrogen substitution in the ellipticine heterocycle is an important if not unique feature for the particular effect of the aza-analogues of ellipticine. Furthermore, they suggest that, in contrast to ellipticine derivatives, these compounds require an activation step before exhibiting cytotoxicity. PMID- 4016758 TI - Cancer occurrence in shipyard workers exposed to asbestos in Hawaii. AB - Because large numbers of persons were employed in United States shipyards during World War II, the long-term risks for cancer associated with asbestos exposure in this setting are of great concern. We report here on the mortality findings after up to 29 years of follow-up on a retrospective cohort of 7971 male Pearl Harbor Naval Shipyard workers, which included more than 3000 men whose employment period spanned the World War II years. Compared with the general population of Hawaii, workers in the shipyard cohort had no increase in total mortality or in total cancer mortality irrespective of the duration of their exposure. However, the risk ratio for lung cancer among workers with at least 15 years of asbestos exposure was 1.4 overall (95% confidence interval, 1.0 to 2.0) and 1.7 for those with a latency interval of 30 or more years (95% confidence interval, 1.0 to 2.5). In addition, seven mesotheliomas occurred between 1977 and 1982 in a subset of the cohort, consisting of 7029 Hawaii residents who are being followed prospectively for cancer incidence. This represented an incidence of 67.3 per million men per year, compared with a rate of 5.8 for the state as a whole. These results suggest that the long-term relative increase in risk for mesothelioma may be even greater than that for bronchogenic carcinoma in this and other cohorts of United States shipyard workers exposed to asbestos. PMID- 4016759 TI - Impaired immune function in patients with xeroderma pigmentosum. AB - The development of contact allergy in sun-exposed skin is markedly impaired in patients with xeroderma pigmentosum as compared to the responses in healthy control subjects. The degree of this immunological impairment is directly related to the severity of the cutaneous disease. These findings raise the possibility that sunlight-induced alterations of immune function may be involved in the marked susceptibility of these patients to the development of nonmelanoma skin cancer. PMID- 4016760 TI - Continuous infusion of high-dose 1-beta-D-arabinofuranosylcytosine: a phase I and pharmacological study. AB - High doses of 1-beta-D-arabinofuranosylcytosine, administered as a continuous i.v. infusion, were evaluated in a Phase I trial in 14 patients with advanced solid tumors. 1-beta-D-Arabinofuranosylcytosine was given at 250 mg/sq m/h for infusions of 12 to 36 h. The mean steady state 1-beta-D-arabinofuranosylcytosine plasma level was 19.6 microM with a range of 9 to 59 microM. The principal toxicity was myelosuppression. An infusion of 18 h was well tolerated by most patients. A Phase II dose of 250 mg/sq m/h for 24 h can be used if platelet support is available. This dose schedule may be useful in the treatment of hematological disorders or in clinical combinations with DNA-damaging agents in the treatment of solid tumors. PMID- 4016761 TI - A nontoxic system for 41.8 degrees C whole-body hyperthermia: results of a Phase I study using a radiant heat device. AB - A Phase I study of whole-body hyperthermia (WBH) (52 treatments/12 patients) was completed with no significant clinical toxicity. The study incorporated a thermal dose escalation scheme from 39.5 degrees-41.8 degrees C for up to 151 min. A radiant-heat device was utilized for producing WBH. During WBH, patients were sedated; endotracheal intubation was not required. No changes in cardiovascular, respiratory, hematological, or biochemical indices requiring clinical intervention occurred during the study. We conclude the radiant-heat device coupled with a defined pharmacological approach to WBH with appropriate patient screening yields a system for 41.8 degrees C WBH which is safe and efficient, is not labor intensive, and does not require general anesthesia and endotracheal intubation. This system is appropriate for a multimodality approach to various systemic cancers. PMID- 4016762 TI - Generation of tumor cell-reactive human monoclonal antibodies using peripheral blood lymphocytes from actively immunized colorectal carcinoma patients. AB - The use of human monoclonal antibodies (MCA) in the detection and treatment of human cancer has been limited by the apparent scarcity of MCA to tumor cell surface antigens. Using peripheral blood lymphocytes from autologous tumor immunized patients, we isolated 36 MCA that react to sections of colorectal carcinoma. Twenty of these human MCA appear to be directed against cell surface antigens. Two-thirds of the human MCA-producing cell lines were diploid human B cells rather than human-mouse heterohybridomas. Direct antibody-binding assays performed with the MCA indicated that they recognized antigenic determinants preferentially expressed on tumor cells. Experiments with paired specimens of air dried, dissociated colon tumor cells and normal colonic mucosa cells suggested that the MCA bound significantly more to the cell surfaces of tumor cells than to the surfaces of normal colonic mucosa cells. Similarly, tests with a panel of cryostat sections of paired colon tumor and normal colonic mucosa showed that MCA bound to the tumor cells and not to the normal colonic mucosa. None of the MCA bound to cells from frozen sections of normal breast, stomach, liver, skeletal muscle, or skin. Furthermore, the human MCA did not react with carcinoembryonic antigen and human erythrocyte antigens as measured by various techniques. Our data also demonstrated that these transformed B-cells and hybridomas were stable producers of human MCA. Thus, our studies show that these tumor-specific human MCA may have the specificity and stability necessary for in vivo evaluation of their use in the detection and treatment of cancer. PMID- 4016763 TI - Biological nature of the effect of ascorbic acids on the growth of human leukemic cells. AB - The effects of L-ascorbic acid (LAA) on the in vitro growth of human leukemic colony-forming cells (L-CFC) were analyzed for all acute nonlymphocytic leukemia patients from whom bone marrow aspirates were received by this laboratory for cell culture study. Among 259 cases, 163 could be directly evaluated for LAA effect. L-CFC growth enhancement was noted in 53 (33%) and suppression in 28 (17%), with overall 50% of patients affected by LAA. Among 34 normal bone marrows tested, none were enhanced by LAA while 8 (24%) were suppressed. While caution is needed in interpreting L-CFC suppression by LAA, L-CFC enhancement is clearly significant. Two isomers of LAA, D-isoascorbic acid and D-ascorbic acid, which have weaker antiscorbutic activity than that of LAA, also produced the L-CFC growth-enhancing effect, but to a lesser degree than that of LAA. A dose-response study also substantiated that D-ascorbic acid was definitely less effective than was LAA. Since D-ascorbic acid is the true optical isomer of LAA and has identical physicochemical properties as does LAA, this differential effect is clearly of biological nature. This study indicates that L-CFC growth suppression by LAA is observed in one-sixth of leukemic patients, L-CFC enhancement in one third of patients, and that L-CFC growth enhancement is a clearly significant finding with a biological mechanism as the basis. PMID- 4016764 TI - Workshop on ataxia-telangiectasia heterozygotes and cancer. PMID- 4016765 TI - Adenocarcinoma of unknown primary origin: treatment with vindesine and doxorubicin. AB - Adenocarcinoma of unknown primary origin (ACUP) is a common oncologic problem for which there is no standard therapy. Forty-two patients with metastatic tumor were identified as having ACUP after extensive evaluation failed to reveal a primary site of disease. They were treated with an investigational chemotherapy regimen consisting of vindesine and doxorubicin. Of the 38 evaluable patients, six (16%) had major responses to chemotherapy. The median duration of response was 4 months. The median survival of the responding patients has not been reached, but is greater than 8 months. The median survival of the nonresponding patients was 6 months. Vindesine and doxorubicin were well tolerated. The major toxicity was leukopenia, with a median wbc count nadir of 2600/mm. We conclude that the combination of vindesine and doxorubicin has some activity in ACUP, but does not improve the response rate seen with other regimens. PMID- 4016766 TI - High-dose etoposide in the treatment of relapsed primary brain tumors. AB - Twenty-four patients with relapsed primary intracranial tumors were treated with high-dose etoposide (600-1000 mg/m2). All patients had received previous radiotherapy and 15 had had previous chemotherapy. The treatment was well tolerated, with little toxicity. Only one patient showed a partial response, which was maintained for 78 weeks. Four patients had stable disease, for a median of 15 weeks. Etoposide failed to show useful activity in relapsed brain tumors. PMID- 4016767 TI - Phase I study of divided-dose vinblastine in advanced malignancy. AB - Thirty-one patients with advanced malignancy received vinblastine as an iv bolus at 0 and 48 hours of a 21-day cycle. Divided-dose vinblastine may be given with acceptable toxicity in heavily pretreated patients; leukopenia and neuropathy were the dose-limiting toxic effects. One patient with breast cancer and one with ovarian cancer responded. Serum vinblastine levels with this program approximate those achieved by a 5-day continuous infusion of vinblastine in standard dose. PMID- 4016768 TI - Phase I-II clinical trial of thymidine, 5-FU, and PALA given in combination. AB - Twenty-eight patients with advanced adenocarcinoma were treated with a combination of thymidine, 5-FU, and PALA. PALA (1 g/m2) was given on the first day, followed on the second day with 30 g of thymidine and 150-300 mg/m2 of 5-FU given simultaneously through two iv sites. Responses were seen in two of 17 patients (12%) with colorectal adenocarcinoma. One response was complete and one was partial. The gastrointestinal tract and CNS were the sites of dose-limiting toxic effects. Myelosuppression was observed only at 5-FU doses of 250 and 300 mg/m2. PMID- 4016769 TI - Metabolic effects of gallium nitrate administered by prolonged infusion. AB - Gallium nitrate was recently found to be effective treatment for resistant cancer related hypercalcemia. In vitro and in vivo experiments have suggested that the drug directly inhibits calcium resorption from bone; however, the overall effects of gallium nitrate on calcium balance were unknown. We have completed metabolic balance studies in four patients who received this drug by prolonged infusion. All patients were in positive calcium balance while receiving the drug. Each patient also showed a substantial decrease in urinary calcium excretion. Serum phosphorus decreased in all four patients. There was no change in phosphorus, sodium, chloride, or magnesium balance or in creatinine clearance. We conclude that prolonged infusions of gallium nitrate reduce urinary calcium excretion and that the hypocalcemic effect of this drug is primarily due to inhibition of calcium resorption from bone. Thus, the drug may prove useful in reducing accelerated bone resorption in patients with bone metastases or chronic cancer related hypercalcemia. PMID- 4016770 TI - Promotion of daunorubicin uptake and toxicity by the calcium antagonist tiapamil and its analogs. AB - Studies were performed with the anthracycline-responsive P388 murine leukemia cell line, and with P388/ADR, a subline selected for doxorubicin resistance. In the P388/ADR cell line, the observed 100-fold daunorubicin resistance is associated with an outward drug transport system which can be inhibited by several calcium antagonists, eg, verapamil and nifedipine. An examination of compounds related to tiapamil, a verapamil analog, has identified a structure which is tenfold more effective than verapamil at potentiating anthracycline accumulation and responsiveness in P388/ADR cells. At no nontoxic level of any calcium antagonist examined was it possible to wholly reverse the degree of daunorubicin resistance found in the P388/ADR cell line. PMID- 4016771 TI - Increased glutathione-S-transferase activity in a cell line with acquired resistance to nitrogen mustards. AB - A Walker 256 rat mammary carcinoma cell line (WR) resistant to bifunctional nitrogen mustards has been shown to have an approximate twofold increase in bulk glutathione-S-transferase activity compared to the parent cell line. Substrate specificity studies suggest that higher levels of Yb subunit contribute to the increased activity. By exposing WR cells to additional chlorambucil, either as a single concentration (50 micrograms/ml) or at 5 micrograms/ml for 10 days, transferase activity was further increased by up to three times the normal WR level. By using colony-forming assays, mitotic index depression, or trypan blue exclusion, the increased transferase activity could be correlated with an increase in resistance of these cells to either subsequent chlorambucil or a different bifunctional nitrogen mustard, phosphoramide mustard. PMID- 4016772 TI - Stability of the in vivo P388 leukemia model in evaluation of antitumor activity of natural products. AB - The stability of the P388 mouse leukemia model over 15 years was examined. Eleven natural products and one synthetic compound (5-FU) tested repetitively under the same conditions of dose and schedule were associated with no significant change in their activity. The P388 model, used in conjunction with other in vivo and in vitro tumor models, continues to be of value in the anticancer drug screening process. PMID- 4016773 TI - Phase I study of bisantrene in acute nonlymphoblastic leukemia. AB - A phase I study of bisantrene using a daily injection for 5 days was undertaken in adult patients with relapsing acute nonlymphoblastic leukemia. Seventeen patients received 27 courses, with daily doses ranging from 75 to 250 mg/m2. Although gastrointestinal toxicity and alopecia were rare, hematological toxicity occurred in 85% of the patients. There was cholestasis unrelated to infectious events in 27% of the courses, as well as reversible renal failure in eight of 27 evaluable courses. Responses (complete + partial) were obtained in 35% +/- 10% of the patients. The recommended dose for phase II study is 200 mg/m2/day X 7. PMID- 4016774 TI - Phase II study of elliptinium in advanced breast cancer. AB - A group of 74 patients with advanced breast cancer received elliptinium as second or third-line treatment (100 mg/m2/week). The objective response rate was 19% (30% in soft tissue metastases), lasting from 3 to 12 months. This drug appears to have no marrow toxicity. Mild to moderate nausea and mouth dryness were the most frequently encountered side effects. Hemolysis occurred in five patients who had an IgM antibody and represents the dose-limiting toxicity. Cumulative renal toxicity (World Health Organization, grade 2) was observed in one of ten patients who had received greater than 2000 mg of elliptinium. PMID- 4016775 TI - Phase II trial of diaziquone in advanced large bowel carcinoma in previously treated and untreated patients: a Southwest Oncology Group Study. PMID- 4016776 TI - Subrenal capsule assay: feasibility of transporting tissues to a central facility for testing. PMID- 4016777 TI - Interferon and doxorubicin in renal cell carcinoma. PMID- 4016778 TI - Phase II study of mitolactol in advanced malignant melanoma. PMID- 4016779 TI - Phase II evaluation of bisantrene in patients with advanced renal cell carcinoma. PMID- 4016780 TI - Acute cardiac failure from doxorubicin cardiotoxicity provoked in relation to second-look laparotomy. PMID- 4016781 TI - Combination of lomustine and cimetidine in the treatment of a patient with malignant glioblastoma: a case report. PMID- 4016782 TI - Acute ECG changes during cyclophosphamide infusion in a patient with bronchogenic carcinoma. PMID- 4016783 TI - Local toxicity from iv administration of Baker's antifol. PMID- 4016784 TI - 5-FU infusion in advanced colorectal cancer: a comparison of three dose schedules. AB - Ninety-four patients with advanced colorectal adenocarcinoma were treated by continuous iv 5-FU infusion on three different dose schedules. Thirty-three patients received a 72-hour infusion of 5-FU (30 mg/kg/24 hours) every 3 weeks (Group A); 31 received a 72-hour infusion of 5-FU (30 mg/kg/24 hours) every 2 weeks (Group B); and 30 received a 48-hour infusion of 5-FU (30 mg/kg/24 hours) every week (Group C). Although this was a sequential nonrandomized study of the dose schedules, the groups were comparable with respect to various prognostic factors. Response rates were as follows: Group A--three patients had minor response (9%) and 30 had no response (91%); Group B--five patients achieved partial response (16%), nine had minor response (29%), and 17 had no response (55%), and Group C--one patient achieved complete response (3%), eight achieved partial response (27%), five had minor response (17%), and 16 had no response (53%). The median survival time for Group A was 9 months, for Group B was 9.5 months, and for Group C was 14 months. Intensifying the dose schedule of 5-FU by increasing the frequency of administration has significantly improved response rates. A prolongation of the median survival time of patients treated with a 48 hour infusion at 1-week intervals was noted, although this was not statistically significant. PMID- 4016785 TI - Prospectively randomized toxicity study of high-dose versus low-dose treatment strategies for lymphoblastoid interferon. AB - It is unclear from preliminary laboratory studies whether a high- or a low-dose interferon treatment strategy is optimal. As part of an ongoing study of mechanisms of interferon action, we have evaluated toxicity in a two-arm protocol in which patients were randomly assigned to receive lymphoblastoid interferon by either a low-dose treatment strategy (2 X 10(6) units/m2 daily X 28 days then daily X 5 days every other week by im injection) or a high-dose treatment strategy (5 X 10(6) units/m2 by continuous iv infusion over 24 hours, escalating by 5 X 10(6) units/m2/day as tolerated over 10 days, repeated every 28 days). The main toxic effects in both arms were fever, fatigue, and anorexia. Marked interpatient differences within each dose arm were greater than differences between arms. Additional significant toxic effects included nausea and vomiting, hypotension, leukopenia, thrombocytopenia, and evidence of hepatic toxicity. Minor changes in serum electrolytes were noted. Coagulation studies were normal. The dose-limiting toxic effect for the high-dose arm was myelosuppression. Median maximum tolerated dose among high-dose strategy patients was 18 X 10(6) units/m2, but there was marked interpatient variation. We conclude that both dose schedules were relatively well-tolerated. Because of individual variation in tolerance, high-dose treatment should include a dose escalation strategy. PMID- 4016786 TI - Mitomycin and tamoxifen versus mitolactol, doxorubicin, and tamoxifen in patients with previously treated breast cancer. AB - One hundred thirty patients with previously treated advanced breast cancer were treated in a cooperative trial to investigate the effect of mitomycin plus tamoxifen (MT) and to compare its relative value to combination therapy with mitolactol, doxorubicin (ADM), and tamoxifen. An additional 76 patients who had had prior exposure to ADM were randomized to receive MT or MT plus fluoxymesterone. MT versus mitolactol, ADM, and tamoxifen was not significantly different in efficacy; however, there were significant differences in toxicity. This study showed that MT is an effective and acceptable second-line treatment for advanced breast cancer. PMID- 4016787 TI - Alternation of chemotherapy and radiotherapy in cancer management. I. Summary of the Division of Cancer Treatment Workshop. PMID- 4016788 TI - Recombinant alpha-2 interferon in the treatment of hairy cell leukemia. AB - We treated 14 patients with hairy cell leukemia, 13 of whom had progressive disease, with recombinant alpha-2 interferon administered sc at 2 X 10(6) units/m2, three times per week. Thirteen patients were evaluable for response. All evaluable patients responded within 6-8 weeks. After a minimal treatment duration of 6 months and a maximal of 12 months, three patients have achieved complete response and ten have achieved partial response. With a median treatment duration of 10 months, the responding patients' hematologic parameters are continuing to improve, and no responding patients have relapsed. This outpatient self-administered regimen is well-tolerated, with mild fever, myalgias, and headache usually resolving within 2 months. Although the optimal regimen and the mechanism of action are unknown, recombinant alpha-2 interferon may be the treatment of choice for patients whose disease progresses after splenectomy or who are not surgical candidates. PMID- 4016789 TI - Phase I study of vinblastine and verapamil given by concurrent iv infusion. AB - Overcoming resistance to chemotherapy is an important goal in cancer treatment. In many systems, resistance to anthracyclines and vinca alkaloids correlates with a diminished intracellular content of drug. In P388 leukemia and Ehrlich ascites tumor, an active outward transport of anthracyclines and vinca alkaloids occurs. Calcium channel blockers, such as verapamil, inhibit this active outward transport and increase intracellular content of vinblastine and anthracyclines in cells resistant to vinca alkaloids and anthracyclines, respectively. We report a phase I trial of vinblastine (1.5 mg/m2 daily as iv continuous infusion X 5 days) in 17 patients and concurrent verapamil in escalating doses. Verapamil was administered as a loading dose (0.02-0.1 mg/kg) followed by a maintenance infusion (0.036-0.18 mg/kg/hour) for 5 1/2 days with continuous cardiac monitoring. There was no apparent augmentation of vinblastine toxicity when vinblastine and verapamil were given concurrently. ECG change was the dose limiting toxicity. At 0.12 mg/kg/hour, five of nine patients developed first degree heart block (mean P-R interval, 0.32 seconds; range, 0.23-0.52 seconds). Junctional rhythms were noted in two of 17 patients. Reversible nonspecific T wave changes were seen in four of 17 patients. Blood pressure and left ventricular ejection fractions (ultrasonic) were not altered. Five of 17 patients had wbc count nadirs less than 2000/mm3, and two of 17 patients had platelet count nadirs less than 100,000/mm3. Four patients experienced neurotoxicity. A mean vinblastine concentration of 2.2 ng/ml (0.55 nM) and a mean verapamil concentration of 290 ng/ml (0.45 microM) were achieved with the concurrent 5-day infusion. The tolerable levels of verapamil obtained appear to be less than those which were reported to inhibit vinblastine efflux in vitro. Additional in vitro experiments at the tolerable doses of vinblastine and verapamil are recommended. PMID- 4016790 TI - Phase I clinical trial of mitozolomide. AB - Mitozolomide (NSC-353451; CCRG 81010; M and B 39565) is a novel potential anticancer agent that was selected for phase I study on the basis of broad spectrum activity in mouse tumors. Initially, mitozolomide was given iv as a short infusion to 37 patients in doses ranging from 8 to 153 mg/m2. Nausea and vomiting was dose-related but was not severe. The dose-limiting toxic effect was thrombocytopenia at doses greater than 115 mg/m2, and recovery from the thrombocytopenia was delayed up to 8 weeks. Partial responses were seen in two patients with adenocarcinoma of the ovary. The pharmacokinetics of mitozolomide showed that the half-life of the intact drug in the plasma was between 1 and 1.3 hours. The area under the curve was proportional to the dose administered. Mitozolomide is well-absorbed; therefore, future studies are recommended using a single-dose schedule orally or iv. In the phase I study reported here, a dose of 115 mg/m2 appeared to be safe, but additional studies have shown that when given orally to an older population, most patients experienced thrombocytopenia less than 50,000 cells/mm3. The recommended dose using current data is 90 mg/m2 iv or orally. PMID- 4016791 TI - Phase II trial of lymphoblastoid interferon in metastatic malignant melanoma. AB - Thirty-three patients with metastatic malignant melanoma, some of whom had received previous chemotherapy, immunotherapy, or radiotherapy, were entered in a trial of three different doses and schedules of administration of lymphoblastoid alpha interferon. The overall response rate was 9%; some patients had long lasting response and two achieved complete response. There was no clear advantage to any one regimen. Dose-related flu-like syndrome, granulocytopenia, hepatocellular enzyme elevation, and anemia were observed as the most common toxic effects. Interferon deserves further study in the treatment of malignant melanoma. PMID- 4016792 TI - Phase II study of human lymphoblastoid interferon in patients with advanced renal carcinoma. AB - Twenty-two patients with measurable metastatic renal carcinoma were treated with human alpha lymphoblastoid interferon (Wellferon) (3 million units/m2 of body surface area) im three times a week for 6 weeks; 21 were evaluable for response and toxicity. One patient had a partial regression of disease lasting 39 weeks and another had a minor response. Six patients had partial or minor response in one area but no change in the disease elsewhere (mixed response); they were classified as having stable disease. An additional seven patients had no change in measurable disease and in six the disease progressed. The tumor regressions by metastatic site were four of 14 patients, pulmonary; three of four, soft tissue; one of nine, bone (? soft tissue); none of three, mediastinal; none of four, renal; none of five, liver; and none of ten, other abdominal sites of tumor. The side effects were fever (101 degrees F-103 degrees F), chills, malaise, anorexia, minor (10%-20%) decrease in performance status, and weight loss. We concluded that interferon had some activity against metastatic renal carcinoma, although clinically useful responses were quite infrequent. While lung metastases appeared to be more responsive than those at other sites, careful examination of the data suggests that this simply reflects differences in the bulk of the metastatic disease. Smaller metastases appear more likely to respond than bulky metastases. PMID- 4016793 TI - High-performance liquid chromatographic and enzyme-inhibition assays of methotrexate concentrations in serum from patients receiving high-dose therapy: tight binding of some methotrexate to a protein that could be dihydrofolate reductase. AB - In the serum of patients receiving high-dose methotrexate (MTX), concentrations of the drug were monitored using both high-performance liquid chromatographic (HPLC) and enzyme-inhibition assays. In samples obtained greater than or equal to 24 hours after drug application, the HPLC assay measured higher MTX concentrations than the enzyme-inhibition assay. In 72-hour samples, the increase was usually greater than 200%. This difference was not observed in serum spiked with MTX. While the HPLC assay needs sample cleanup, ie, protein precipitation, the enzyme-inhibition assay routinely employs native serum. When MTX was measured in the supernatant with the enzyme inhibition assay, the results equaled those obtained with the HPLC procedure. In patient serum, MTX eluted from a Sephadex G 75 column in two fractions. One had the same retention volume as free MTX and could be assayed directly. The other had a retention volume like dihydrofolate reductase. In this fraction, MTX could only be determined after denaturing proteins. Only small amounts of tightly bound MTX were found in the serum of patients on intermediate-dose therapy (500-600 mg/m2). The observation that after high-dose MTX therapy part of the MTX in patient serum is strongly bound to a protein which could be DHFR raises the question as to the source and fate of this complex. Furthermore, the present finding has clinical relevance to the extent that the accepted limits for risk of MTX toxicity are based on methods using native serum. However, any procedure employing protein precipitation for sample cleanup may grossly overestimate active MTX serum concentrations, especially in the 72-hour serum samples. PMID- 4016794 TI - Deoxyguanosine enhancement of cytarabine nucleotide accumulation in human leukemia cells. AB - We studied the effect of deoxyguanosine (dGuo) on cellular cytarabine (ara-C) nucleotide accumulation of the human leukemia cell line K562 and of bone marrow blast cells derived from patients with acute nonlymphocytic leukemia. Exposure of cells in culture to dGuo increased ara-C nucleotide accumulation measured in cell lysate, with an average increase of 386% (range, 242%-537%) of control in the presence of 500 microM dGuo. Maximal elevation occurred after 8 hours of exposure and remained constant through 48 hours. dGuo also enhanced deoxycytidine nucleotide accumulation, but dGuo enhancement favored accumulation of ara-C nucleotides over dCyd nucleotides. In cell cycle kinetic studies using flow cytometry, dGuo slowed accumulation of cells with apparent S-phase DNA content in a concentration-dependent fashion. However, neither the rate nor the magnitude of this effect correlated with the increase in ara-C nucleotide accumulation. Since the increase in ara-C nucleotide accumulation caused by dGuo could be prevented by 5 micrograms/ml of cycloheximide, this process appears to require new protein synthesis. Although these data suggest that the elevation of ara-C nucleotide accumulation caused by dGuo may represent induction of enzyme synthesis, other possibilities are discussed. Exposure of bone marrow blast cells obtained from patients with acute nonlymphocytic leukemia to dGuo for 16 hours in liquid culture also increased ara-C nucleotide accumulation. In six of seven studies, exposure to dGuo in concentrations from 50 to 500 microM increased ara-C nucleotide accumulation from 160% to 3400%. These data suggest that dGuo may alter ara-C metabolism in a clinically useful fashion. PMID- 4016795 TI - Continuous infusion of vinblastine for advanced hormone-refractory prostate cancer. AB - Thirty-nine patients with metastatic prostate cancer refractory to hormonal manipulation were treated with vinblastine by continuous infusion. The dose was 1.5 mg/m2 daily for 5 days. A 21% response rate was obtained. Eight patients, two with visceral metastasis, one with nodal disease, and five with osseous metastasis achieved objective response. The median duration of response was 28 weeks. Myelosuppression was the major side effect: the median leukocyte count nadir was 2.8 X 10(3)/ml and the median platelet count nadir was 184 X 10(3)/ml. PMID- 4016796 TI - Cyclophosphamide/etoposide: effective reinduction therapy for children with acute nonlymphocytic leukemia in relapse. AB - Reinduction therapy consisting of cyclophosphamide (250 mg/m2 orally daily for 4 days) followed by etoposide (250 mg/m2 iv daily for 3 days) was administered to 14 children with refractory or recurrent acute nonlymphocytic leukemia. Five complete remissions were achieved in eight patients who had relapsed in the bone marrow 1-27 months after cessation of initial therapy, which included anthracyclines, cytarabine, etoposide, and 5-azacitidine. Reinduction attempts were unsuccessful in patients who had failed to achieve an initial remission and in those whose relapses occurred while receiving therapy. Toxicity, including myelosuppression and mucositis, was within acceptable limits. This drug combination deserves further assessment in therapeutic protocols for patients with acute nonlymphocytic leukemia. PMID- 4016797 TI - Recombinant leukocyte alpha interferon in advanced ovarian carcinoma. AB - Recombinant leukocyte alpha interferon (rIFN-alpha A; Hoffmann-La Roche, Inc) was administered to 15 patients with recurrent or persistent ovarian carcinoma. All patients had been previously treated with surgery and combination chemotherapy including cyclophosphamide (15 patients), doxorubicin (14), and cisplatin (14). Three patient had also previously undergone radiation therapy. At the start of therapy the largest tumor size was less than or equal to 2 cm in four patients and greater than 2 cm in 11. Interferon was administered in three times weekly for 8 weeks at a dose of 20 X 10(6) units/m2, with average drug levels of 2267 pg/ml 6 hours after im injection. In three patients (20%), the dose had to be reduced by 50% because of drug toxicity. Side effects included fever (greater than 101 degrees F) in 12 patients, fatigue in ten, headache in two, diarrhea in two, and reversible myelosuppression in five. Of the 15 patients, one had mixed response lasting 12 weeks, two had stable disease of 8 weeks' duration, and 12 had disease progression. PMID- 4016798 TI - Phase II trial of elliptinium in advanced renal cell carcinoma. AB - Forty patients with advanced renal cell carcinoma were treated with elliptinium by a weekly infusion of 100 mg/m2. Of 38 evaluable patients, five had an objective response (13.2%). Average response duration was 8 months (range, 5-11). The major dose-limiting toxic effect was induction of antielliptinium antibodies, with the risk of intravascular hemolysis. Elliptinium has modest activity in advanced renal cell cancer and does not produce myelosuppression. PMID- 4016799 TI - Phase II evaluation of melphalan in adenocarcinoma of the pancreas. PMID- 4016800 TI - Phase II clinical trial of diaziquone in bronchogenic carcinoma. PMID- 4016801 TI - Difficulty of interpreting disease-free interval curves when substantial numbers of patients die in remission. PMID- 4016802 TI - Extensive tissue ulceration due to apparent sensitivity reactions to mitomycin. PMID- 4016803 TI - Chemotherapy in advanced gastric cancer. PMID- 4016804 TI - Transcatheter thrombolysis in cancer patients. AB - Arterial thrombolysis was successfully accomplished in 15 of 18 (83%) cancer patients by the continuous intraarterial transcatheter administration of streptokinase (70 units/kg/h or 5000 u/h and/or urokinase (400-500 u/kg/h) over 24-96 h. In 16 of these patients, the arterial thrombosis was a complication of transcatheter infusion of chemotherapeutic agents or embolization therapy. A combination of streptokinase, urokinase and heparin (10,000-25,000 U/day) was utilized without significant side effect and was effective in all 8 patients receiving treatment. Creating a tunnel through the clot, daily monitoring of the catheter with repositioning when necessary, and adjusting the type and dose of thrombolytic agent aided the therapeutic management. PMID- 4016805 TI - Intraarterial ethanol as a long-term occlusive agent in renal, hepatic, and gastrosplenic arteries of pigs. AB - The renal, hepatic, or gastrosplenic arteries of eleven juvenile pigs were selectively injected intraarterially with 95% ethanol to evaluate its efficacy as an agent for use in permanent occlusion and infarction of the vascular bed supplied by the injected artery. A dose of 2.2 cc/5 kg (1 cc/5 lb) of 95% ethanol was injected over 30-45 sec. The animals were then killed at 1 to 91 days and all pigs demonstrated tissue infarction and vascular occlusion. Our results confirm that ethanol is an effective agent for the infarction of organs and that complications can result if catheter placement is not precise and normal tissue is inadvertently perfused. PMID- 4016806 TI - Emphysematous cholecystitis as a complication of hepatic arterial embolization. AB - We describe a case of emphysematous cholecystitis that developed 2 weeks after hepatic arterial embolization. Angiographers should be alert to the possibility of this complication developing under conditions when the cystic artery is not visualized on the post embolization arteriogram while present on the diagnostic study before embolization. PMID- 4016807 TI - Hemorrhagic renal angiomyolipoma: superselective renal arterial embolization for preservation of renal function. AB - A 35-year-old woman with tuberous sclerosis and known bilateral renal angiomyolipomas presented with shock due to massive hematuria arising from the left kidney. The cause of bleeding was diagnosed angiographically as arising from a left upper pole renal artery aneurysm within the tumor. Cessation of bleeding and clinical stabilization occurred without deterioration of renal function after superselective embolization of the dorsal segmental renal artery with a single 5 mm Gianturco coil. PMID- 4016808 TI - Long-term results after sclerotherapy of the spermatic vein in patients with varicocele. AB - Ninety-seven patients received transfemoral sclerotherapy of the spermatic vein for varicocele. After observation for 2 to 5 years, follow-up was available in 69 patients (71.2%), in 11 of whom the procedure failed (16.0%). Complications during angiography (N = 12, 12.4%) or sclerotherapy (N = 31, 32.0%) did not require hospital treatment. At least one parameter of the spermiogram was improved in 25 of 32 patients (78.1%). Forty-four of 69 patients (63.8%) treated because of a childless marriage, and whose wives were not known to be infertile, had a pregnancy rate of 47.7%. Thi method may be considered equal to surgical procedures in achieving venous occlusion; furthermore it is simple and can be used on an outpatient basis without anesthesia. PMID- 4016809 TI - Liver necrosis after hepatic dearterialization in pigs. AB - In nine pigs, the livers were dearterialized by a combination of distal occlusion of the hepatic artery with Ivalon (polyvinyl alcohol foam) particles of 150-250 mu and proximal occlusion of the common hepatic artery with Gianturco coils. Necrosis of at least 90% of the liver developed in eight pigs. One pig with less extensive liver necrosis had developed an effective collateral circulation to a large part of the liver. Patency of the portal venous system did not prevent extensive infarction of dearterialized liver tissue. PMID- 4016810 TI - Volumetric analysis of right ventricular cadaver models viewed in axially angled projections. AB - Axial cinematography of 15 cadaver cast models of the right ventricle was performed, using 16 different real and simulated single and biplane axial oblique projections. Heart volumes were then calculated by Dodge's area-length method and Ferlinz' method. In our volumetric studies of models, the smallest positive deviation from real volumes was 3.7% with the simulated long-axis projection (SLP2), evaluated from the frontal plane and calculated by the area-length method. Volumetric determinations of most usefulness, as ranked by mean differences and mean quadratic deviations, were achieved with the simulated long axis projection, (SLP1--ranked third and SLP2--ranked first), evaluated from the frontal plane and calculated by Dodge's method; with biplane orientation and calculation by Ferlinz' method (SLP1 + SLP1C1-- ranked seventh, deviation from real volumes was 23%, SLP2 + SLP2C2--ranked fourth). We found that single-plane hepatoclavicular projection (HCP--ranked second and fifth), calculated by Dodge's or Ferlinz' method, as well as single-plane sitting-up projection (SUP--ranked sixth), calculated by the area-length method, were also acceptable for right ventricular volume measurements. PMID- 4016811 TI - Mapping of activation changes within the acutely ischaemic canine specialised conduction system. AB - Ligation of the anterior septal artery was used to produce acute ischaemia of the specialised conduction system in ten dogs. Activation times at selected positions within the specialised conduction system were recorded. Marked delays of activation occurred between several discrete anatomic sites within the specialised conduction system. This study demonstrates that extremely slow conduction is common in localised areas of the acutely ischaemic infra-nodal conduction system. Heterogeneity of myocardial activation secondary to changes of speed of the conduction during acute septal ischaemia is postulated as a mechanism facilitating the occurrence of malignant ventricular arrhythmias. PMID- 4016812 TI - Intrathoracic and abdominal pressure variations as an efficient method for cardiopulmonary resuscitation: studies in dogs compared with computer model results. AB - Intrathoracic pressure variations are currently proposed as the main flow generation mechanisms in standard and modified cardiopulmonary resuscitation (CPR) techniques. A method of changing pressure within the thorax and abdomen without any degree of heart compression was developed and tested in dogs. Intrathoracic and abdominal pressure waves were induced by cyclic inflation and deflation of the lungs and of perithoracic and periabdominal balloons. Various modes of CPR, depending on the rate of cycling, the use of a periabdominal balloon inflation, and a delay between the abdominal and thoracic pressure waves, were studied during ventricular fibrillation. During artificial systole (high intrathoracic pressure phase), the pressure which developed in the right ventricle (96.7 +/- 20.5 mmHg) was higher than the pressure in the aorta (89.3 +/ 20.5 mmHg, p less than 0.001). In artificial diastole (low intrathoracic pressure phase), the right ventricular pressure (11.7 +/- 2.6 mmHg) was lower than the aortic pressure (17.5 +/- 3.3 mmHg, p less than 0.001). The average flow in the carotid artery was 21.7 +/- 7.8 ml . min-1, which was 18 +/- 6% of the baseline carotid flow before CPR. Three different factors were found to improve the efficiency of CPR: periabdominal balloon inflation simultaneous with the intrathoracic pressure waves; increased frequency of the pressure waves from 60 to 100 cycles per minute; and inflation of the periabdominal balloon 50 to 100 ms before the thoracic balloon. Blood-gas and acid-base balance analysis during CPR revealed well-oxygenated arterial blood with a marked respiratory alkalosis and a slowly developing metabolic acidosis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4016813 TI - Morphometric study of the total and perfused arteriolar and capillary network of the rabbit left ventricle. AB - A method has been developed to simultaneously and regionally determine several morphometric indices of both the total and perfused arteriolar and capillary beds of the rabbit heart on a quantitative basis. A high molecular weight fluorescein isothiocyanate (FITC) dextran, was injected into the femoral vein of an anaesthetised open chest rabbit. The hearts were removed and frozen in liquid N2 within 14 s after this injection. Sections, 2 micrometers thick, were obtained from the left ventricular wall and the fluorescence photographed to detect perfused arterioles and capillaries. The sections were then stained to visualise the total arteriolar and capillary network. Standard morphometric techniques were employed to study the total and perfused microvasculature. The method was validated to show that it did not alter the microvasculature of the heart, that both the total and perfused microvasculature could be visualised, and that there was little tissue shrinkage. The study found no significant subepicardial vs subendocardial differences in either the total or perfused capillary of arteriolar networks. The total capillary bed had very much larger morphometric indices than the total arteriolar bed. The percentage of the microvasculature perfused ranged from 55 to 64% of the capillary and 51 to 56% of the arteriolar beds for the various indices. Thus at least a part of the control of capillary perfusions is at the level of the arteriole. There was an almost twofold functional reserve in the microvasculature of the heart which could be mobilised by asphyxia. PMID- 4016814 TI - Effects of verapamil on the extracellular K+ rise during myocardial ischaemia in dogs. AB - The effects of verapamil on the [K+]o rise produced by myocardial ischaemia were assessed in 26 open chest mongrel dogs. Ischaemia was produced by intermittent occlusion of the LAD artery (15 dogs) or by reduction of flow of the cannulated LAD (11 dogs). Specially constructed valinomycin K+ sensitive electrodes were inserted into the mid myocardium in the central zone of ischaemia (CZ); in the margin (MZ) and in the nonischaemic zone (NZ). Occlusion of the coronary artery under controlled conditions produced significant [K+]o rise, greater in the CZ than in the MZ. During the infusion of verapamil the ischaemic [K+]o rise was substantially reduced in both zones. During controlled 75% reduction of coronary flow the [K+]o reached a plateau that remained stable until reperfusion was re established. During verapamil infusion, the plateau showed a steady decline, both in the CZ and in the MZ. The changes in [K+]o produced by verapamil, during myocardial ischaemia are probably due to: coronary dilatation of the marginal arteries and+or to a reduction of the late cellular K+ conductance due to a decrease in the intracellular Ca2+, produced by verapamil. PMID- 4016815 TI - Adriamycin cardiomyopathy in the rabbit: an animal model of low output cardiac failure with activation of vasoconstrictor mechanisms. AB - Chronic administration of intravenous adriamycin (1 mg . kg-1 twice weekly for 8 weeks) to rabbits resulted in a cardiomyopathy which was similar to that occurring in patients with adriamycin cardiotoxicity. We studied systemic and renal haemodynamics and the activation of vasoconstrictor mechanisms reflected by changes in plasma renin activity (PRA), noradrenaline (NA) and vasopressin (AVP) levels during the development of heart failure in this animal model. By 8 weeks cardiac failure was clearly established. At postmortem all animals had dilated hearts, pleural and pericardial effusions, ascites and hepatic congestion. Heart weights were increased (8.1 +/- 0.7 g in treated animals n = 9 vs 6.0 +/- 0.2 g in controls n = 9 p less than 0.05). Cardiac output (measured by thermodilution) fell at 8 weeks from 799 +/- 61 ml . min-1 to 624 +/- 44 ml . min-1 (n = 6 p less than 0.05) with a parallel fall in mean blood pressure from 85 +/- 2 mmHg to 75 +/- 4 mmHg. Total peripheral resistance rose in four of the six rabbits. Renal blood flow fell from 108 +/- 4 ml . min-1 to 61 +/- 6 ml . min-1 (p less than 0.05) by 8 weeks. Renal vascular resistance increased in all animals. PRA increased from 5.1 +/- 0.5 ng AI . ml-1 . h-1 to 11.6 +/- 2.6 ng AI . ml-1 . h-1 by 4 weeks (p less than 0.05) and remained elevated thereafter.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4016816 TI - Mechanism of hydralazine-induced relaxation of arterial smooth muscle. AB - The effect of hydralazine on contractile responses by various agents has been studied in isolated rat tail artery strips. Hydralazine caused dose-dependent relaxation of contractions produced by 10(-7) mol.litre-1 noradrenaline (N); 10( 7) mol.litre-1 5-HT or 100 mmol.litre-1 KCl, suggesting that the relaxation response is non-specific. CaCl2 dose-response (in the presence of 10(-5) mol.litre-1 N; 10(-5) mol.litre-1 5-HT or 100 mmol.litre-1 KC1) was significantly inhibited by 5 X 10(-4) mol.litre-1 hydralazine in the order: KCl greater than 5 HT greater than N. Hydralazine also inhibited BaCl2 dose-response curve (in K+ depolarised strips); maximal contraction to BaCl2 was depressed by 87%. In other experiments, hydralazine significantly depressed (by 20%) the phasic contractile response to N due to mobilisation of calcium from a membrane-bound pool. D 600, a calcium entry blocker, also caused dose-dependent relaxation of contractile responses to all three agents studied; and inhibited CaCl2 and BaCl2 dose response curves in K+-depolarised media, as well as depressed the phasic contractile response to N in Ca-free media by 17%. These results suggest that in the rat tail artery, hydralazine interferes with Ca2+ influx, as well as release from a membrane-bound pool. PMID- 4016818 TI - Metabolic evidence of inadequate coronary blood flow during closed-chest resuscitation in dogs. AB - Closed-chest cardiopulmonary resuscitation (CPR) produces only small pressure differences across the coronary circulation and relatively little coronary blood flow in dogs with ventricular fibrillation. To determine whether coronary flow during experimental resuscitation is sufficient to maintain aerobic myocardial metabolism, we measured left ventricular adenosine triphosphate (ATP) and lactate concentrations before and immediately after a 20 min period of CPR in six fibrillating dogs. The mean aortic-right atrial pressure difference generated during CPR averaged 5.4 +/- 2.6 mmHg (SEM) and 3.2 +/- 2.6 mmHg at the beginning and end of the 20 min period, respectively. Left ventricular myocardial blood flow (measured with radioactive microspheres) averaged 16.7 +/- 5.7% of prearrest values during the first 10 min of CPR, and 8.5 +/- 4.8% of prearrest values during the second 10 min of CPR. Biopsies after CPR contained less ATP (3.3 +/- 0.1 vs 4.7 +/- 0.5 nmol.mg-1, p less than 0.05) and more than seven times more lactate (14.7 +/- 3.1 vs 1.9 +/- 0.2 nmol.mg-1, p less than 0.01) than control biopsies. We conclude that coronary blood flow during CPR is inadequate relative to myocardial oxygen demands during ventricular fibrillation in dogs. The techniques developed in this study provide a potential means of assessing the effects of experimental interventions on myocardial oxygenation during CPR. PMID- 4016817 TI - Imparied atrial receptor modulation or renal nerve activity in dogs with chronic volume overload. AB - Left atrial receptors with vagal afferents are reset and become less sensitive in dogs with chronic high output congestive heart failure (Zucker et al J Clin Invst 1977;60:323). We determined if the normal reflex inhibition of renal sympathetic nerve activity (RNA) which occurs in response to left atrial distension is altered in dogs with chronic volume overload produced by an aorto-vena caval fistula (AVF). In addition, we examined the ability of the arterial baroreflex to alter RNA. In normal dogs, left atrial distension decreased RNA by 6.8 +/- 1.8% per mmHg change in left atrial pressure (LAP). After carotid sinus denervation (CSD), this inhibition was increased to 10.9 +/- 1.4% per mmHg change in RNA in response to left atrial distension. Vagotomy completely abolished any change in RNA in response to left atrial distension. In contrast, dogs with chronic AVF's demonstrated an increase in RNA in response to left atrial distension by 4.5 +/- 3.9% per mmHg change in LAP. The response of the AVF dogs was significantly different from the normal dogs (P less than 0.005). This was also the case after CSD. Loading and unloading of the arterial baroreceptors with norepinephrine and nitroprusside demonstrated that the modulation of RNA by arterial baroreceptors was similar in AVF dogs compared with normal dogs. The present study demonstrates that chronic volume overload results in a decrease in the peripheral sympathetic inhibitory effects of left atrial receptor stimulation at a time when arterial baroreceptor function is preserved. PMID- 4016819 TI - Mechanism of the negative inotropic action of leukotrienes C4 and D4 on isolated rat heart. AB - Leukotrienes C4 and D4 (LTC4 and LTD4), possible mediators of cardiac dysfunction during inflammatory injury, may depress cardiac function by reducing coronary flow or by exerting a negative effect directly on the myocardium. We used an isovolumic rat heart preparation perfused at constant pressure and measured left ventricular developed pressure (mmHg), coronary flow (ml.min-1), oxygen extraction, and myocardial oxygen consumption and delivery (mumol O2.[gramme dry weight]-1.min-1) during infusion of five doses of angiotensin II, LTC4, LTD4 (approximately 10 to approximately 300 pmol.min-1), and noradrenaline (400 to 2000 pmol.min-1), or perfusion with medium which contained calcium at half concentration. LTC4 and LTD4 were equipotent with angiotensin. At low effective doses, increased oxygen extraction offset the decrease in oxygen delivery, maintaining a stable level of oxygen consumption and left ventricular developed pressure. At the highest doses, angiotensin, LTC4 and LTD4 reduced coronary flow from 21 to 15, 21 to 13, and 21 to 13 ml.min-1, respectively. And, despite greater oxygen extraction of 59%, 58% and 65% for angiotensin, LTC4 and LTD4, left ventricular developed pressure fell from a baseline of 120 mmHg to 113, 106 and 92, respectively. In contrast, low calcium perfusion reduced left ventricular developed pressure (126 to 92) and oxygen extraction (46 to 30%) without changing coronary flow or oxygen delivery. These results suggest that LTC4 and LTD4 are potent coronary vasoconstricting agents which depress cardiac function by limiting oxygen delivery. PMID- 4016821 TI - A new device for the efficient pulverisation and extraction of myocardial biopsies for high energy phosphate analysis. AB - We developed a new device for processing frozen myocardial biopsies. Frozen samples of 20 to 50 mg were dropped into a 25 ml stainless steel centrifuge tube held in a custom-made aluminium container precooled in liquid nitrogen. A stainless steel pestle attached to a stainless steel disk was driven by a modified heavy-duty staple gun to pulverise the tissue rapidly at low temperatures. The tissue powder was extracted with 0.3N PCA at 0 degree C in the centrifuge tube which was then transferred to a Sorvall super-speed centrifuge. Values for adenosine triphosphate (ATP) were 5.6 +/- 0.7 mumol . g-1 wet weight (mean +/- SD). Creatine phosphate (CP) yield was 12.2 +/- 3 mumol . g-1 wet weight. The % recovery of an added internal standard for ATP was 86 +/- 18% and for CP 90 +/- 16% with the new method. PMID- 4016820 TI - Vasopressin-induced coronary constriction at low perfusion pressures. AB - We studied the effects of intracoronary vasopressin on the relationship between pressure and flow in the coronary circulation of anaesthetised swine. In addition to measurements at control levels, diastolic pressure-flow relationships were constructed from steady-state points below a coronary pressure of 50 mmHg, where endogenous vasodilatation is strongly stimulated. At baseline pressures, flow fell 28% with maximal vasopressin effect. At all levels of diastolic pressure below 50 mmHg vasopressin also decreased flow, eg, at 30 mmHg flow was depressed by 40%. The slope of the steady-state pressure-flow relationship fell from 1.21 to 0.75 ml.min-1.mmHg-1. The diastolic pressure at which coronary flow ceased rose slightly from 13 to 15 mmHg. Intracoronary adenosine completely prevented vasopressin's effect, and the vasodilator response to adenosine was not attenuated by simultaneous administration of vasopressin. The porcine coronary circulation will constrict in response to vasopressin, not only at normal perfusion pressure, but also at low levels when metabolic vasodilatation is intense. Our study has implications about the therapeutic use of vasopressin, and demonstrates interaction of vasoactive stimuli in the coronary circulation. PMID- 4016822 TI - Effects of myocardial catecholamine accumulations on arrhythmias following ischaemia and reperfusion. A problem of open-heart surgery. PMID- 4016823 TI - Alcohol and the heart. PMID- 4016824 TI - Practice of gynecology in the elderly. AB - All practitioners must become more familiar with the practice of gynecology in the elderly in order to better serve their patients, of whom an increasing proportion are geriatric gynecologic patients. Advances in medical technology have increased the average life span, and better understanding of "senescent changes" may make it possible to improve the quality of life as well. PMID- 4016825 TI - Possible involvement of epinephrine in the cardiovascular effect of naloxone in humans. AB - The opioid-receptor antagonist naloxone was administered intravenously in a 0.8 mg bolus to five healthy volunteers, aged 21 to 31, in a double-blind study designed to investigate the effect of endogenous opioids on blood pressure, heart rate, and urinary excretion of catecholamines in healthy adults. Three hours after administration of naloxone there were significant increases in systolic blood pressure (P less than 0.001) and heart rate (P less than 0.05). The amount of epinephrine excreted in urine during the four hours after administration of naloxone or placebo was significantly higher (P less than 0.05) in subjects given naloxone. These effects support the hypothesis that an endogenous opioid system is involved in the regulation of systolic blood pressure and heart rate in healthy adults. The results also indicate that adrenally released epinephrine could mediate the cardiovascular effect of endogenous opioids. PMID- 4016826 TI - Interrelationship between gastric acidity and gastrin concentration in patients with duodenal or gastric ulcer and in healthy subjects. AB - Although increased gastric acidity may be important in the pathogenesis of duodenal ulcer, it has a less well-defined role in the formation of gastric ulcers. The present study was undertaken to determine (1) the 24-hour intragastric pH and serum gastrin profiles of 31 patients with duodenal ulcers, eight patients with gastric ulcers, and seven healthy volunteers and (2) the effect of 600 mg of cimetidine BID on these measurements. There was considerable overlap of basal acid output values in the three groups, and mean values did not differ significantly. In response to pentagastrin, the peak acid output was significantly higher in the duodenal ulcer group than in the gastric ulcer or healthy group. There were no intergroup differences in intragastric hydrogen ion (H+) activity after meals, overnight, and over 24 hours, when all subjects received placebo. However, the pH values remained at or above 4.0 for a longer period during the night in the gastric ulcer patients than in the duodenal ulcer patients or healthy subjects. There were no intergroup differences in basal gastrin concentration, but the postprandial gastrin response after each meal was higher in the gastric ulcer group than in the other two groups. In the gastric ulcer group, cimetidine suppressed H+ activity at all times; in the duodenal ulcer and healthy groups, cimetidine suppressed H+ activity only after breakfast, overnight, and over 24 hours. Cimetidine enhanced the serum gastrin response to food to a greater extent in the ulcer patients than in the healthy subjects. In the healthy subjects, the ratio of H+ to gastrin (H+:G) was higher than in the duodenal or gastric ulcer patients but was suppressed only minimally by cimetidine, whereas cimetidine markedly suppressed the H+:G ratio in both groups of ulcer patients. Patients with a history of duodenal or gastric ulcers differed from healthy volunteers in their food-stimulated gastrin response and in their H+:G ratio when treated with cimetidine. Intergroup differences in gastrin response to food, but not in intragastric pH in response to food, suggests that defective control of or response to gastrin may be important in the pathogenesis of acid-peptic disease. Cimetidine, which was effective in H+ suppression in all subject groups, may alter the sensitivity of the parietal cells to gastrin in patients with duodenal or gastric ulcers. PMID- 4016827 TI - Comparative efficacy of cefadroxil and cefaclor in the treatment of skin and soft tissue infections. AB - A ten-day, randomized, open-label study was conducted to compare the efficacy of 1,000 mg of cefadroxil once daily and 250 mg of cefaclor TID in 200 black patients with skin and soft-tissue infections caused by microorganisms sensitive to these cephalosporins. Statistically, the clinical results with each drug were not significantly different: 91% efficacy with cefadroxil and 95% efficacy with cefaclor. The important difference between cefadroxil and cefaclor is the remarkably longer half-life of cefadroxil, which makes once-a-day dosing possible and offers greater patient convenience and the likelihood of better compliance. In an analysis of compliance, only 2% of the patients in the cefadroxil group (20 capsules given to each patient) returned unused capsules; 77% in the cefaclor group (30 capsules given to each patient) returned unused capsules. PMID- 4016828 TI - Comparative incidence of side effects of a wax-matrix and a sustained-release iron preparation. AB - The side effects of a wax-matrix iron preparation and a sustained-release iron preparation were compared in a single-blind study of 181 subjects. Evaluations after four and eight weeks of therapy revealed moderate or severe side effects in 52% of the subjects who received the sustained-release preparation but in only 25% of those who received the wax-matrix preparation. Further analysis of the data demonstrated fewer side effects overall among patients who received the wax matrix preparation. These findings suggest that the wax-matrix preparation is better tolerated than the sustained-release preparation. PMID- 4016829 TI - Prospective, randomized comparison of the efficacy and safety of netilmicin clindamycin and tobramycin-clindamycin in the treatment of serious systemic infections. AB - Fifty-three patients with documented or suspected mixed flora infections were randomly assigned to receive either netilmicin or tobramycin in combination with clindamycin. Data from 36 patients with 43 documented infections yielding 102 clinical isolates were evaluated for efficacy. In the 18 patients receiving netilmicin-clindamycin, 90% of the infections responded favorably and 96% of the pathogens were eliminated. In the 18 patients receiving tobramycin-clindamycin, 81% of the infections resolved and 88.5% of the pathogens were eliminated. Forty nine patients were included in the safety analysis. The incidence of nephrotoxicity was similar in both groups (netilmicin, 20%; tobramycin, 21%). Auditory toxicity occurred less frequently in the netilmicin-clindamycin group (4.5%) than in the tobramycin-clindamycin group (21.7%). These results demonstrate that both the netilmicin-clindamycin and the tobramycin-clindamycin combinations are comparable in efficacy and in potential for causing nephrotoxicity. In this study, however, netilmicin was considerably less ototoxic than tobramycin. PMID- 4016830 TI - Single-dose mezlocillin prophylaxis in emergency cesarean section. AB - A single 5-gm dose of mezlocillin or a placebo was administered intravenously 30 minutes before surgery to patients undergoing emergency cesarean section. The assignment of drug or placebo was randomized. Postoperative morbidity occurred in 62.5% of patients receiving placebo and in 18.4% of those receiving mezlocillin (P less than 0.001). The incidences of febrile morbidity, endometritis, and urinary tract infection were significantly lower in the group given mezlocillin. Other benefits of antibiotic prophylaxis included a shorter hospital stay and no serious infections in the group given mezlocillin. PMID- 4016831 TI - Effects of adult rat brain extracts on cultures of mouse brain cells: consequence of the depletion in a carbohydrate-binding fraction. PMID- 4016832 TI - Qualitative and quantitative changes of acetylcholinesterase in the central nervous system of mice during low and high dose treatment of alpha-chlorohydrin. PMID- 4016833 TI - Short term regulation of hepatic 3-hydroxy-3-methylglutaryl-coenzyme A reductase during pregnancy and perinatal development in the rat. PMID- 4016834 TI - Chromatin structure and transcription activity during maturation of intestinal epithelial cells. PMID- 4016835 TI - Growth dependence of nuclear glycogen synthesis in mutant HD33 Ehrlich-Lettre ascites tumor cells. PMID- 4016836 TI - Developmental regulation of protein synthesis in Hymenolepis diminuta: 2 dimensional electrophoretic and fluorographic analysis of polypeptide synthesis in formation of brush border membranes. PMID- 4016837 TI - Pattern analysis of the heterogeneous distribution of succinate dehydrogenase in single rat hepatic lobules. PMID- 4016838 TI - [Advantages and disadvantages in modern dialysis therapy]. PMID- 4016840 TI - [Sensitivity and specificity of oncologic cytology of the efferent urinary tract]. PMID- 4016839 TI - [Water for hemodialysis]. PMID- 4016841 TI - [Centralization of the study of urinary concretions in East Germany]. PMID- 4016842 TI - [Can America afford to treat uremia? Washington, 2-4 May 1984]. PMID- 4016843 TI - [Ethics and diagnosis]. PMID- 4016844 TI - [New diagnostic methods and approaches in gastroenterology]. PMID- 4016845 TI - [Relation of total blood cholesterol and HDL-cholesterol]. PMID- 4016846 TI - [Circulating immunocomplexes in chronic hepatitis B]. PMID- 4016847 TI - [Changes in magnesium levels in erythrocytes, serum and urine in healthy persons after physical exertion]. PMID- 4016849 TI - [An anniversary to remember]. PMID- 4016848 TI - [Morphologic findings in liver tissue in primary sclerosing cholangitis]. PMID- 4016850 TI - [Administration of androgens to transsexual females. I. Effect on somatometric changes]. PMID- 4016851 TI - [Deviant and non-deviant sex delinquents]. PMID- 4016852 TI - [The effect of the family environment on the self-confidence, the identification process and choice of a life partner in sexually dysfunctional men]. PMID- 4016854 TI - [Effective acquisition of primary sources of information using reprints]. PMID- 4016853 TI - [A sexual attitude test]. PMID- 4016855 TI - [The effect of military arming on the socioeconomic situation throughout the world]. PMID- 4016856 TI - [Verification of factors in longevity in epidemiological studies in selected regions in Bohemia]. PMID- 4016858 TI - [Is there a perspective for the spectral analysis of electrocardiograms?]. PMID- 4016857 TI - [Buerger's disease in women]. PMID- 4016859 TI - [Leukemia and the HLA-C locus]. PMID- 4016860 TI - [Hepatest-3, a kit for the rapid screening for hepatitis B virus surface antigens using a 3d generation test]. PMID- 4016861 TI - [Characteristics of medical ethics in childhood and adolescence]. PMID- 4016862 TI - [Question marks and exclamation marks surrounding mitochondrial heredity]. PMID- 4016863 TI - [Rational approach to radiodiagnositic examinations. Thoughts on a publication of the World Health Organization]. PMID- 4016864 TI - [Genetic risk in microbiological laboratory work]. PMID- 4016865 TI - [Occupational genetic risk in oncologic radiotherapy nurses]. PMID- 4016866 TI - [Borderline states in psychiatry]. PMID- 4016867 TI - [Are the new cephalosporins "dangerous antibiotics"?]. PMID- 4016868 TI - [Symptomatic liver porphyria with a familial incidence]. PMID- 4016869 TI - [Legionnaires' disease in a 37-year-old man]. PMID- 4016870 TI - [What is and what is not Mobitz II]. PMID- 4016871 TI - [Gouty osteopathy. Clinical case report of the disease with an unusual course]. PMID- 4016872 TI - [The role of universities in the strategy for achieving the goal of the WHO, "Health for All by the Year 2000)]. PMID- 4016873 TI - [The concept of man in Marxist-Leninist philosophy and its significance in medicine. Overcoming the natural science concept of medicine]. PMID- 4016874 TI - [Changes in indicators of humoral immunity in patients with insulin-dependent diabetes]. PMID- 4016875 TI - [The relation of glycosylated proteins in blood to the state of compensation in diabetes mellitus]. PMID- 4016877 TI - [Do we know the mechanism of tumor transformation?]. PMID- 4016876 TI - [Comparison of the physical fitness of forestry workers who work with portable power saws and heavy machinery]. PMID- 4016878 TI - [Psychosocial orientation in medicine with emphasis on clinical oncology]. PMID- 4016879 TI - [Spinal epidural carcinoma metastasis]. PMID- 4016880 TI - [Early diagnosis of malignant melanoma of the skin]. PMID- 4016881 TI - [A stable erythrocyte diagnostic preparation for the indirect hemagglutination reaction in toxoplasmosis]. PMID- 4016882 TI - [Man and the environment as a problem of medical hygiene]. PMID- 4016883 TI - [Principles of modeling biomedical systems on computers]. PMID- 4016884 TI - [Pathogenesis of liver encephalopathy]. PMID- 4016885 TI - [The kinetics of Ujoviridine as an indicator of the functional capacity of the liver]. PMID- 4016886 TI - [Hemocoagulation changes in patients with type I diabetes mellitus in renal insufficiency]. PMID- 4016887 TI - Histochemistry and ultrastructure of adrenergic and acetylcholinesterase containing nerves supplying follicles and endocrine cells in the guinea-pig ovary. AB - The autonomic nerve supply of the guinea-pig ovary was investigated by a combination of light- and electron microscopy. At the light-microscopic level, adrenergic fibres were identified due to their formaldehyde-induced fluorescence. In addition, the ovary contained acetylcholinesterase-positive fibres. In all parts of the ovary, the adrenergic fibres were most numerous. At the ultrastructural level it was possible to identify the adrenergic nerve terminals with the aid of the false adrenergic transmitter, 5-hydroxy-dopamine. Thus, large numbers of adrenergic terminals, characterized by their content of 50-60 nm, electron-dense synaptic vesicles, were seen within the interstitial gland, where they formed close contacts with the endocrine cells (membrane-to-membrane distance, 20-100 nm). The follicular theca externa was also richly supplied by adrenergic nerves. At this location, close contacts (50-100 nm) were identified between the nerve terminals and the smooth muscle-like cells. Very few adrenergic nerve fibres were present in the theca interna of follicles or in the corpus luteum. Non-adrenergic nerve terminals, characterized by electron-lucent synaptic vesicles of 50-60 nm diameter, were observed together with the adrenergic fibres. They were always present in much lower numbers than the latter. No "p-type" nerves were identified by electron microscopy. PMID- 4016888 TI - Capsaicin-induced inhibition of axoplasmic transport is prevented by nerve growth factor. AB - Capsaicin injected into the scrotal skin of rats was observed to induce a decrease in the amount of horseradish peroxidase (HRP) transported in the pudendal nerve to the sixth lumbar dorsal root ganglion on the pretreated side. This was seen as a decrease in the number of HRP-labelled neurones compared to the control side. A morphometric study confirmed that the effect of capsaicin was exerted predominantly on the small neurones. Injection of nerve growth factor (NGF) into the pudendal nerve prevented the deleterious effects of capsaicin, thereby suggesting a possible site of action and mechanism for the effect of capsaicin on peripheral nerves. PMID- 4016889 TI - Ultrastructural morphometry of parathyroid cells in rats of different ages. AB - Parathyroid glands of newborn to 1-year-old male Sprague-Dawley rats were fixed by perfusion or by immersion, and prepared for electron microscopy. Parathyroid glands fixed by immersion exhibited parenchymal cells with variable ultrastructure, indicating that these cells were in different stages of the proposed secretory cycle in parathyroid cells. In contrast, parathyroid cells of glands fixed by perfusion were uniform in ultrastructure, suggesting that all cells were in the same stage of secretory activity. Parathyroid glands of 3-, 4-, 6-, 8- and 10-week-old rats also were fixed by perfusion and analysed by electron microscopic morphometry. These data demonstrated an increase in cell volume and in surface area of the membrane compartments concerned with parathyroid hormone secretion: these changes were not related to variations in serum calcium concentration. Both the qualitative observations and the quantitative data do not favour the idea of a secretory cycle in rat parathyroid cells. PMID- 4016890 TI - Measurements of intracellular calcium. PMID- 4016891 TI - Using quin2 in cell suspensions. PMID- 4016892 TI - Cell calcium measurement with electron probe and electron energy loss analysis. PMID- 4016893 TI - Intracellular levels and distribution of Ca2+ in digitonin-permeabilized cells. AB - Digitonin and other saponins can be used to selectively permeabilize the plasma membrane of a wide variety of cells without significantly affecting the gross structure and function of Ca2+-sequestering organelles such as mitochondria and endoplasmic reticulum. These characteristics have allowed digitonin to be used in the determination of the intracellular levels and distribution of Ca2+, as well as the measurement of Ca2+ fluxes by organelles "in situ". Studies conducted with several different types of digitonin-permeabilized cells indicate that the endoplasmic reticulum functions as a high affinity and low-capacity intracellular Ca2+ buffer, whereas mitochondria operate as a relatively low affinity but high capacity Ca2+ buffering system. However, recent findings suggest that mitochondria have a comparable affinity for net Ca2+ uptake in the presence of physiological concentrations of polyamines. The use of permeabilized cells has also been important in the identification of the endoplasmic reticulum as a site at which the recently discovered second messenger inositol trisphosphate acts to bring about an increase in the cytosolic free Ca2+ concentration. Thus, the selective permeabilization of cells with digitonin and its analogues has been a powerful yet simple tool in the study of intracellular Ca2+ homeostasis. PMID- 4016894 TI - Measurement of intracellular calcium ion activity with neutral exchanger ion sensitive microelectrodes. AB - Micropipettes filled with the neutral liquid ion exchanger ETH 1001 can be used to make microelectrodes that are sensitive to cytoplasmic levels of Ca2+. They are high resistance electrodes, so that care is required in order to record the low current signal. The electrodes often yield 10-15 mV change between intracellular Ca2+ activities of 10(-6) and 10(-7) M, according to a log relation. The microelectrodes are non-destructive, even in rather small cells, and can be used to monitor Ca2+ changes during experimental interventions. PMID- 4016895 TI - Aequorin entrapment in mammalian cells. PMID- 4016896 TI - [A mathematical model of the age-specific prevalence of hypertension]. PMID- 4016897 TI - [Epidemiological study of the incidence rate of athletic injury in junior high school students]. PMID- 4016898 TI - [A compound catalytic model with both simple and reversible types and its applications in disease surveillance]. PMID- 4016899 TI - [Morbidity of leptospirosis in Meng-lian County in Yunnan Province]. PMID- 4016900 TI - [Epidemiological survey of enteritis caused by Campylobacter]. PMID- 4016901 TI - [Epidemiology of leprosy in Zigong District of Sichuan Province]. PMID- 4016902 TI - [Dynamic study on the incidence and mortality of esophageal cancer in Lin County, 1959-1981]. PMID- 4016903 TI - [Survey of sudden death among 370,000 people in rural areas]. PMID- 4016904 TI - Serologic survey of hepatitis B surface antigen among the healthy population in Zimbabwe. PMID- 4016905 TI - A follow-up and case tracing exercise. PMID- 4016906 TI - Malacoplakia of the urinary tract (a case report and review of the literature). PMID- 4016907 TI - Dramatic recovery from complete hemiplegia and decorticate rigidity caused by severe hypoglycemia. PMID- 4016908 TI - Bioavailability of proprietary corticosteroid containing ointments. PMID- 4016909 TI - Nutritional status of an urban community in Zimbabwe. PMID- 4016910 TI - Urban pedestrian accidents and the efficacy of a counter-measure. PMID- 4016911 TI - Characteristics of patients attending Harare Hospital with incomplete abortion. PMID- 4016912 TI - Cryptococcus neoformans meningitis. PMID- 4016913 TI - Gastroenteritis due to campylobacter jejuni in Lagos, Nigeria. PMID- 4016915 TI - The more serious effects of schistosomiasis. PMID- 4016914 TI - Colonoscopy--experience in Zimbabwe. PMID- 4016916 TI - Teaching the management of terminal illness in Zimbabwe. PMID- 4016917 TI - Pain characteristics of painful ophthalmoplegia (the Tolosa-Hunt syndrome). AB - Pain characteristics of the Tolosa-Hunt syndrome were abstracted from the observations of five patients with repeated incidents of painful ophthalmoplegia. The pain was experienced either as pressure behind the ophthalmoplegic eye or as boring pain in one orbital region, fluctuating in intensity, sometimes worsening to knife stab-like pain in the eye. The unilateral pain did not shift side during a solitary incident of painful ophthalmoplegia and was never completely absent. The pain was increased when the eyes were strained, when cold wind blew against the face, and when a change in the weather took place. It was accompanied by a feeling of swelling in the affected region, but not by nausea nor vomiting. Conventional headache drugs provided little relief. All cases experienced tenderness when pressure was applied to the ipsilateral supraorbital foramen. The pain was suggested to be related to an increased load on the impaired venous blood flow in the region of the superior orbital fissure. PMID- 4016918 TI - The so-called "partial Horner syndrome" in cluster headache. An editorial. PMID- 4016919 TI - Classic migraine attack complicated by confusional state: EEG and CT study. AB - We report electroencephalographic and clinical observations in one attack of classic migraine, accompanied by a confusional state. The ictal EEG showed slow waves over the left hemisphere, the abnormality gradually clearing up during the four days following the attack. A brain CT scan was normal during the attack and also a few days later. A possible relationship between impairment of consciousness during the attack and left hemispheric metabolic dysfunction is discussed. PMID- 4016920 TI - The cluster-tic syndrome and its surgical therapy. AB - The term cluster-tic syndrome (CTS) is used to designate a clinical pain pattern in which symptoms of cluster headache (CH) and tic douloureux (TD) coexist. The TD elements of the attack occur in paroxysms of many seconds or minutes, always affect the maxillary or mandibular divisions of the trigeminal nerve, with spread into the ophthalmic division in some cases, and may be triggered by slight superficial stimuli. These features may occur independent of CH elements but more often the two blend together. Four patients with CTS unresponsive to medication underwent surgery. Blood vessels were found to cross compress the trigeminal nerve in all four patients and the nerve was decompressed. A similar condition was found affecting the facial nerve in two of the three patients in whom that nerve was explored and the facial nerve was decompressed in these two. The TD component of the CTS disappeared after surgery in all four patients. The CH component of the syndrome returned after surgery but in a modified form. In three patients, the CH changed from what had been chronic cluster to infrequent episodic cluster periods; additionally in two patients, the duration of cluster was shorter and the pain was of lesser severity. PMID- 4016921 TI - Cluster headache: histamine skin tests in the painful area. AB - Histamine skin tests were performed in the painful area and on the opposite side in ten cluster headache patients. The studies were carried out with and without local anaesthesia. No differences between histamine skin response in the painful region compared with the contralateral side were revealed. This study concerns the part of the triple response which is the result of a direct action of histamine on the skin vasculature (mediated by both H1 and H2) histaminergic receptors, i.e. wheal and redness, and the flare, which is the result of neurohumoral mechanisms. PMID- 4016922 TI - Cluster headache: clinical efficacy of lithium salts in a haemodialysis treated patient. AB - Over the last ten years the efficacy of lithium salts in cluster headache has been well demonstrated. Our patient, who had been suffering from cluster headache for approximately 30 years, had been in haemodialysis treatment for the last ten years for chronic renal failure. Moreover, he was affected by heart failure and peptic ulcer. The patient was currently under therapy with Digitalis, Isorbide dinitrate, and ranitidine and was dialyzed three times a week for a total of five hours each time. Neither prophylactic headache therapy nor high doses of analgesic drugs had proved effective. Although this patient was in haemodialysis, lithium treatment was indicated. The administration of lithium carbonate 300 mg during dialysis days and 150 mg during non-dialysis days improved the attacks. Complete recovery from the attacks was obtained when the serum levels of lithium reached the therapeutic range. No side effects were noted. PMID- 4016923 TI - Migraine v. transient cerebral ischemia. Proceedings from an international congress, Rome, Italy, 30 November-1 December, 1984. PMID- 4016924 TI - The effects of flunarizine in experimental models related to the pathogenesis of migraine. AB - Two new hypotheses suggest that the key pathology in migraine has a neuronal origin. A pivotal role is assigned to brain hypoxia (1) and spreading depression (SD) (neuronal depolarization spreading gradually over the cortex) (2). Flunarizine has been tested both against brain hypoxia and SD. Its potent antihypoxic properties in animal models led to its use as a prophylactic drug in migraine therapy. Earlier experiments suggested that flunarizine shortened recovery after neuronal depolarization. Recent experiments suggest that flunarizine may enhance the threshold for the elicitation of SD. Finally, it is often unclear whether the effects observed with flunarizine are due to a vascular or a direct neuronal effect. Therefore, a study was made to show whether flunarizine affected hypoxia-induced alterations in synaptic function in slices of hippocampus held in vitro. At physiological drug concentrations in brain, flunarizine improved post-hypoxic recovery of synaptic function. A direct neuronal protective effect was thus demonstrated. PMID- 4016925 TI - Neuroendocrine and behavioral effects of flunarizine in young and old rats. AB - Neuroendocrine and behavioral effects following an acute or chronic treatment with the calcium antagonist, flunarizine, have been studied in young and old rats. Both in young and old rats, acute administration of flunarizine (2 mg/kg) failed to modify plasma prolactin (PRL) levels, as measured at 8.00 a.m., 4.00 p.m. and 12.00 p.m. A chronic treatment with flunarizine (0.5 mg/kg/day, for 20 days) in young rats was followed by a relevant, albeit statistically not significant, increase in plasma PRL levels, as measured at 8.00 a.m. and 4.00 p.m., and by a significant decrease at 12.00 p.m. A shift of nocturnal peak of plasma PRL levels from 12.00 p.m. to 4.00 a.m. was observed in these animals. A chronic treatment with flunarizine in old rats was followed by a significant increase in plasma PRL levels, as measured at 12.00 p.m. The acquisition of active avoidance behavior was studied in a shuttle-box test. Acute administration of flunarizine failed to change the performance of young and old rats in acquiring the behavioral response, as measured by the total number of conditioned avoidance responses (CARs) and the percentage of learners. When flunarizine was administered chronically, a decrease in CARs and learners was observed both in young and old rats. This was accompanied by a significant increase in the percentage of animals that froze during the acquisition session. No significant effect was found in young and old rats tested in a "despair" test after a chronic treatment with flunarizine. PMID- 4016926 TI - Migraine and cerebral hypoxia: a hypothesis with pharmacotherapeutic implications. AB - It is postulated that a migraine attack is a specific reaction pattern to an episode of focal cerebral hypoxia. This hypothesis holds that any type of focal brain hypoxia (and thus not only a vasospasm) may provoke a migraine attack. Indeed, as hypoxia is a result of an imbalance between energy supply and energy use, the former can be decreased and/or the latter be increased. Spreading cortical depression, leading to the aura, is believed to be another consequence of brain hypoxia occurring in classical migraine. There are no other genuine differences between classical and common migraine, according to the cerebral hypoxia theory. The latter theory may improve our understanding of the mode of action of antimigraine drugs. Certain calcium entry blockers have a direct protective effect on brain hypoxia, but some other pharmacotherapeutic approaches may also prevent cerebral hypoxia via an effect on brain metabolism, vasomotion or platelet behavior. PMID- 4016927 TI - Erythrocyte deformability changes in headache patients under flunarizine treatment. AB - Changes in erythrocyte deformability (ED) parameters have been investigated in 36 patients suffering from different forms of headache (classic and common migraine; migraine with interval headache; chronic tension headache) and treated with flunarizine (10 mg/day at bedtime). Patients were carefully selected in order to avoid any possible interference with the parameters under study, and smoke and drug use in particular (symptomatics included) were considered as criteria for exclusion from the trial. Controls of ED parameters were planned before treatment and after 20 and 35 days. Baseline ED alterations were present only among patients with chronic tension headache, but flunarizine treatment was able to positively modify ED parameters in these patients, as well as in migraine cases that showed normal baseline ED values. No correlation was found between patients' characteristics and baseline ED values, nor between ED changes under treatment and therapeutic effects of flunarizine. PMID- 4016928 TI - Telethermographic investigations in migraine patients before and after flunarizine treatment. AB - Fifty migraine patients were tested prior to and after a three-month period of flunarizine treatment (10 mg per day) by means of a new computerized telethermography apparatus. At completion of therapy a new computerized telethermography was carried out. The telethermographic data obtained showed an improvement in 70% of the cases; for the other patients telethermographic relevant modifications were not singled out. PMID- 4016929 TI - Headache in transient ischemic attacks (TIA). AB - The evaluation of headache in patients with transient ischemic attacks (TIA) has various sources of difficulty, the definition of TIA being the most relevant. The classical definition needs to be supplemented with a normal CT scan if a misleading diagnostic statement is to be avoided. The clinical features of 90 patients suffering from TIA and who had contrast-enhanced CT scans are reported. Headache occurred in 30% of the patients. Headache prevailed in patients with vertebrobasilar TIA compared with carotid TIA (p less than 0.05). Headache prevailed as a preceding (24 h) and/or concomitant sign compared with other neurological symptoms (77.8% of the patients). Headache was ipsilateral, in the anterior half of the head in the carotid TIA and in the posterior half of the head in the vertebrobasilar TIA. In about 50% of the patients generalized non localized headache occurred. Headache usually preceded the neurological symptoms in cases of arterial occlusion (20 carotid, 3 vertebral artery), usually appearing during or after the attack in cases without arterial occlusion. Only 2 cases out of 20 with positive CT scan had headache. These two patients suffered from a rather large hypodense lesion. The other 18 patients showed lacunar lesions. Different hypotheses concerning the physiopathology of the headache associated with TIA are discussed. PMID- 4016930 TI - Influence of flunarizine on the altered electronystagmographic (ENG) recordings in migraine. AB - Flunarizine, a slow-channel calcium blocker, appeared to be effective in the prophylactic treatment of common and classic migraine in 29 out-patients included in a double-blind clinical trial. After a two-month placebo period, half the patients were treated with flunarizine, 10 mg a day for up to 120 days, half with placebo. Electronystagmographic (ENG) recordings were performed at the end of the common placebo period and after two and four months of treatment, respectively. There was a significant reduction in Headache Unit Index (HUI) and Headache Unit Index Corrected (HUIC) (42% and 40.5% respectively) in the flunarizine-treated group but not in the placebo group. Analgesic intake was reduced and intensity of pain was unchanged in both groups throughout the trial. ENG data were not significantly affected by flunarizine treatment. PMID- 4016931 TI - Brainstem auditory evoked potentials in migraine patients in basal conditions and after chronic flunarizine treatment. AB - BAEPs have been studied in a group of 20 migraine subjects before and after chronic flunarizine treatment. No statistically significant modifications of neurophysiological parameters have been observed. We confirm flunarizine effectiveness in migraine treatment. PMID- 4016932 TI - Pupillary and vascular effects of calcium antagonists in migraine. AB - In migraine patients the effect of calcium antagonists (flunarizine, verapamil and nifedipine) on both venous and pupillary neuromuscular functions, as well as on blood pressure have been evaluated. A single oral dose of flunarizine (10 mg) and verapamil infusion (50 micrograms/ml/min) increased venous compliance. Verapamil also counteracted dose-dependent dopamine induced venoconstriction. Nifedipine (10 mg orally) reduced mean arterial pressure in upright position in migraineurs but not in controls. In addition, chronic treatment with flunarizine (10 mg for 2 weeks) induced a transient miotic effect and a reduction of tyramine induced mydriasis. These findings demonstrated that calcium antagonists affect vascular and extravascular structures. It is postulated that, in migraine, calcium entry blockers may prevent exaggerated responses to catecholaminergic stimulation. PMID- 4016934 TI - "Chronic daily headache" ("cefalea cronica quotidiana"). PMID- 4016933 TI - Hormonal and metabolic changes induced by flunarizine therapy: preliminary results. AB - The effect of 30-days of flunarizine (5 mg/day) therapy on pituitary, B pancreatic, gonadic and adrenal function was studied in five adolescents with common migraine. Baseline concentration of growth hormone was significantly reduced after flunarizine therapy. The response of prolactin to thyrotrophin releasing hormone was significantly increased after flunarizine therapy. The percentages of HbA1 and HbA1c were significantly higher after flunarizine therapy. The drug had no apparent effect on gonadic and adrenal function. Further studies are needed to confirm the effect of flunarizine on the hypothalamus pituitary axis and glucose tolerance. PMID- 4016935 TI - Analysis of outcome predictors of migraine towards chronicity. AB - Long-term migraine evolution is still undefined. The poorest outcome is the transformation from episodic attacks to a pattern of daily attacks or continuous headache with intermittent attacks. We called these cases "chronic migraine". The aim of our study was to investigate whether some clinical variables contributed to migraine chronicity. We interviewed 50 patients with chronic migraine from 2 to 15 years and 90 patients with episodic migraine matched for sex and age as a control group. Univariate analysis revealed two correlations with a chronic outcome: (1) In the control group a significantly higher number of women took oral contraceptives. (2) In the group who developed chronic migraine, there were a greater number of smokers, without reaching statistical significance. The stepwise multiple logistic regression method showed that these two variables influence the prognosis with a maximum likelihood estimate of 65%, hence not much higher than random probability. PMID- 4016936 TI - Focal cerebral ischemia and migraine. AB - Consistent literature data on the cerebrovascular risk in migraineous patients are lacking. Available preliminary clinical data (Italian Cooperative Cross Sectional Case-Control Study) suggest that migraine can hardly be considered a relevant pathogenetic associated risk factor of focal cerebral ischemia. PMID- 4016937 TI - Common migraine versus daily chronic headache: a study of the relationship between depression and anxiety scores, and dexamethasone suppression test. AB - To achieve a better understanding of CH and DCH, we used a multidisciplinary approach evaluating both the depression and anxiety scores and the ability of DEX to decrease plasma cortisol levels in patients with these two forms of headache. The Hamilton rating scale for depression, the Zung test for depression and Stai X2 for anxiety showed scores within the control range in both groups of patients without any statistically significant difference between the groups. The DEX test showed significant cortisol suppression in both groups of patients either at 8 a.m. or at 4 p.m. (after DEX administration, 1 mg orally at 11 p.m. the night before). The results obtained indicate that in CM and in DCH, normal depression and anxiety scores exist in the present of the apparent integrity of the hypothalamic-pituitary-adrenal axis. PMID- 4016938 TI - Antimigraine drugs in the management of daily chronic headaches: clinical profiles of responsive patients. AB - Flunarizine, a Ca-antagonist with demonstrated antimigraine properties, and indoprofen, an anti-inflammatory non-steroidal agent, were used in the treatment of daily chronic headache. Forty-two migraineurs with interval headache (MIH) were treated with flunarizine in a 6-month open trial, while indoprofen was administered to 23 patients with MIH and 7 with chronic tension headache (CTH) in a 2-month, double-blind, cross-over placebo-controlled study. Flunarizine was found effective in over 65% of the patients, while indoprofen was able to improve headache severity in only 30% of the subjects. In the responder patients, the effectiveness of both drugs is more pronounced in MIH, and seems to be ascribable to the ability of the treatments to reduce number and severity of attacks. A higher incidence of previous affective disturbances is found in non-responsive cases. The analysis of factors converting episodic into chronic headache shows slight but not significant differences between responders and non-responders. An impairment of plasma beta-endorphin levels, in the presence of normal ACTH, cortisol and nociceptive RIII threshold values, characterizes daily chronic headache (DCH) patients. Moreover, indoprofen does not significantly affect these biological and neurophysiological parameters independently of the therapeutic response. PMID- 4016939 TI - Life events and headache. AB - We have evaluated the incidence and the gravity of recent and early stressful life events in 149 patients with headache and in 43 healthy controls. The incidence of early stressful events was the same for the headache patients and the controls, and for the three subtypes of headache patients. Patients with headache had undergone more recent stressful events than the control individuals, and the difference was due to patients with migraine. The mean gravity of the recent stressful events did not differ significantly. This probably indicates that appearance of headache is not so much associated with the gravity of the events as with the fact that they have occurred in the lives of patients with other biological and/or psychological characteristics with which the stress interacts. PMID- 4016940 TI - rCBF after TIA and during migraine attacks. AB - TIA is usually caused by embolism from a carotid stenosis. The stenosis has no hemodynamic significance, but recent studies of regional cerebral blood flow have indicated that this occurs in a few cases. Traditionally, TIA are not considered to cause cerebral damage, but CT-studies have revealed a number of silent infarcts and rCBF measurements have shown even more persistent abnormalities of blood flow. In classic migraine, alterations of rCBF are completely different, indicating a mechanism progressing in the cerebral cortex, probably the spreading depression of Leao. Similar blood flow changes are not seen in common migraine, where tomographic rCBF determinations have been normal. PMID- 4016941 TI - On the possible relation of spreading cortical depression to classical migraine. AB - During the first 1 to 2 h of the classical migraine attack a hypoperfusion develops which starts in the posterior part of the brain and progresses anteriorly at a rate of 2-3 mm/min. The hypoperfusion stops at primary sulci outlining major cortical macro- and microstructural changes, but seems not to be inhibited by other changes of the cortical architecture. The low flow regions are cortical and the low flow persists for 4-6 h, until the attack abates. Regions of hyperperfusion are either minor or non-existent. A similar behavior characterizes the velocity and mode of evolution of a cortical spreading depression, a transient perturbation of cortical neuronal function which has profound and long lasting influence on the cortical blood flow. This paper briefly summarizes the arguments which have been put forward in recent years suggesting that spreading depression is a pathogenetic mechanism of migraine. PMID- 4016942 TI - Visual evoked potentials and brainstem auditory evoked potentials in migraine and transient ischemic attacks. AB - A study of brainstem auditory evoked potentials (BAEPs) and pattern reversal visual evoked potentials (VEPs), recorded in intercritical phase, was carried out in 20 subjects (10 suffering from common migraine and 10 suffering from vertebrobasilar TIA) in order to obtain a comparative evaluation of cortical subcortical functions. The data we obtained demonstrate the presence of BAEPs alterations in patients with previous vertebrobasilar TIA: no abnormalities were found in the migraine group. VEPs parameters are normal in both groups. Our data show that the study of the so-called "stimulus-related" potentials, such as BAEPs and pattern reversal VEPs, is useful in evaluating the damage produced by any noxa, while it cannot clearly emphasize individual factors predisposing to a specific pathology, as the absence of specific alterations in migraine patients demonstrates. PMID- 4016943 TI - The use of retinal fluorangiography techniques in the study of cerebral circulation. AB - Retinal fluorangiographic techniques can be employed in the study of cerebrovascular disorders in relation to the embryological, anatomic and functional affinities between the cerebral and retinal circulation. The techniques currently used have been improved by means of the computer analysis of the photographic image, thus allowing qualitative evaluations of the vascular dynamics and quantitative evaluations referred to remarkable variations. These improved techniques can be summed up as follows: equidensitometry with arbitrary colors, computerized fluorangiography for the evaluation of the vascular caliber, computer analysis of mean transit time (m.t.t.). A new type of qualitative evaluation not considering the fluorangiographic image has recently been introduced: the fluorophotometric analysis. PMID- 4016944 TI - NMR imaging in transient cerebral ischemia. AB - NMR has proved useful in the detection of Acute Cerebrovascular Disorders (ACVD), providing information related either to the tissue signal intensity and relaxation times, or to the morphological aspects of cerebral structures. Eighteen patients suffering from ischemic Acute Cerebrovascular Disorders were studied. A comparison between NMR imaging and CT scan was performed. Ischemic lesions, presence of edema, presence of reactive gliosis and anatomical vascular anomalies were found. PMID- 4016945 TI - Correlation between migraine and circulating platelet aggregates. AB - We studied platelet aggregates, by Wu and Hoak's technique, in 73 patients (49 F and 24 M), aged 14-61 (mean age 50.4 +/- 12.2) with migraine. Platelet aggregates were expressed as Platelet Aggregate Ratio (PAR). We consider as pathological PAR values lower than 86. Mean PAR value of migraine patients (78.3 +/- 8.68 SD) was significantly lower (p less than 0.001) than that of 90 control subjects (95.4 +/ 6.15 SD). Normal PAR values were found only in 27.4% of the migraine patients. The patients were divided according to the interval from the last attack: 17 patients were studied in the 1st week (PAR = 73.76 +/- 7.6 SD; 5.8% of the values in the normal range), 15 in the 2nd week (76.6 +/- 7.02 SD; 13.3% of the values in the normal range) and 41 between 15th and 30th day (80.78 +/- 8.78 SD; 29.6% of the patients in the normal range). The mean PAR value of the patients studied during the first week was significantly lower (p less than 0.01) than that of the patients studied between 15th and 30th day. No significant differences were found between the patients with classical, common and complicated migraine. PMID- 4016946 TI - Relevance of prostaglandins in migraine. AB - Prostaglandins (PG), particularly PGE, may be linked to the pathophysiology of migraine in several important ways. PGE1 may "simulate" a migraine attack in healthy volunteers. PGE may be elevated in patients with migraine. In animal experiments and in human infusions, PGEs cause vasodilation and hyperalgesia, both typical reactions of inflammation. The view that vascular headache is an "inflammatory reaction" allows the best concept concerning the local role of PGs and the effectiveness of PG-inhibitors in the treatment of migraine. The local role of PGs may provide a common denominator in several hormonal, neural and other influences on vessels. The common triggers of a migraine attack like menstruation, alcohol and stress influence the PG-system and even the dietary reactions, hormonal influences, sleep and reserpine have some connections with the PG-system. A local role for PGs does not diminish the importance of other pathophysiological mechanisms operating during an attack. On the contrary, PGs may fill in gaps in our understanding of how the overt pain of attacks is produced. PMID- 4016947 TI - Electrocardiographic ST-T wave patterns, extent of coronary artery disease, and left ventricular performance following non-Q-wave myocardial infarction. AB - Subendocardial, nontransmural, or non-Q-wave myocardial infarction (NQM) carries a serious prognosis. Many previous studies of NQMI include only patients without new Q waves at the time of infarction. Since the site of transmural MI (by Q waves) has implications concerning extent of coronary disease (CAD) and left ventricular (LV) dysfunction, we wondered what the extent of CAD and LV dysfunction is among acute MI patients who have neither new nor old Q waves. Furthermore, we sought to determine whether ST-T wave patterns or resting LV ejection fraction (EF), alone or combined, could separate NQMI patients with significant CAD from those with normal or nearly normal coronaries. Therefore, we retrospectively examined angiographic and electrocardiographic data in 55 symptomatic patients with NQMI. ST-T wave patterns on admission were classified as either ischemic (transient ST elevation, persistent horizontal ST depression, or persistent deep T wave inversion) or nonspecific. Eleven patients (20%) had normal or nearly normal coronaries (N); ten patients (18%) had one, seven patients (13%) had two, and 19 patients (34%) had three vessel CAD; eight patients (15%) had left main (LM) disease. Six of the 11 N patients had ergonovine tests and all six were negative. Segmental LV wall motion abnormalities (WMA) were commonly observed; however, diffuse LVWMA were present only among patients with three vessel and LM disease. EF was below 0.50 in 48% of patients with three vessel or LM disease. Although ischemic ST-T wave patterns were more common (P less than 0.05) among patients with significant CAD than among N patients, neither the ST-T wave pattern nor EF, alone or in combination, allowed confident separation of N patients from significant CAD patients. We conclude 1) A large proportion of NQMI patients have LM disease, three vessel disease, or normal or nearly normal coronaries. 2) Despite the absence of Q waves, LV dysfunction is common and the degree of LV impairment is worse among patients with more extensive CAD. 3) NQMI patients who may have normal or nearly normal coronaries cannot be reliably separated from NQMI patients with significant CAD on the basis of ST-T wave patterns or resting LVEF. 4) Coronary angiography appears warranted to assess the extent of CAD in symptomatic NQMI patients. PMID- 4016948 TI - Left main coronary thrombolysis. AB - A patient with acute occlusion of the left main coronary artery in whom streptokinase thrombolysis was successful in reestablishing antegrade flow is reported. A discussion of factors influencing survival and a review of the literature is presented. PMID- 4016949 TI - Injection of contrast medium within the interatrial septum: an unusual complication of right atrial angiography. AB - A 56-year-old male with right ventricular dysplasia underwent right atrial angiography. Though the catheter tip appeared to be in the right atrial cavity, an appreciable amount of contrast medium dissected the interatrial septum, resulting in unusual radiologic and ultrasonic patterns. PMID- 4016950 TI - Ergonovine provocative testing: a double catheter technique. PMID- 4016951 TI - In biology, neither smaller nor larger is necessarily better. PMID- 4016952 TI - Reconstitution experiments show that sequence-specific histone-DNA interactions are the basis for nucleosome phasing on mouse satellite DNA. AB - The molecular basis underlying the sequence-specific positioning of nucleosomes on DNA was investigated. We previously showed that histone octamers occupy multiple specific positions on mouse satellite DNA in vivo and have now reconstituted the 234 bp mouse satellite repeat unit with pure core histones into mononucleosomes. Histones from mouse liver or chicken erythrocytes bind to the DNA in multiple precisely defined frames in perfect phase with a diverged 9 bp subrepeat of the satellite DNA. This is the first time that nucleosome positions on a DNA in vivo have been compared to those found on the same DNA by in vitro reconstitution. Most of the nucleosomes occupy identical positions in vivo and in vitro. There are, however, some characteristic differences. We conclude that sequence-dependent histone-DNA interactions play a decisive role in the positioning of nucleosomes in vivo, but that the nucleosome locations in native chromatin are subject to additional constraints. PMID- 4016953 TI - Radial loops and helical coils coexist in metaphase chromosomes. AB - Histone-depleted chromosomes have revealed a scaffold and loop architecture of metaphase chromosomes. In its simplest form this arrangement contradicts many classical observations suggesting chromosomes have a helical substructure. We have obtained preparations that allow the visualization of several levels of chromosome structure. These images suggest that metaphase packing is achieved by the compaction through helical coiling of a 200-300 nm fiber that is in turn composed of radial loops. These observations imply that any scaffold elements associated with radial loops are not distributed as previously proposed but must follow a complex and more extensive path within the metaphase chromatid. PMID- 4016954 TI - Ribosomal protein production in normal and anucleolate Xenopus embryos: regulation at the posttranscriptional and translational levels. AB - We have studied the regulation of ribosomal protein (r-protein) synthesis in Xenopus anucleolate mutants, which lack the genes for rRNA. The accumulation of mRNA for the two r-proteins analyzed parallels the controls up to stage 30. This mRNA is mobilized onto polysomes and is translated as in normal embryos, but r proteins are unstable in the absence of rRNA to assemble with. A translational control of rp-mRNA distribution between polysomes and mRNPs is observed, but this is not due to an autogenous regulation by r-proteins. After stage 30 the amount of rp-mRNA declines specifically in the mutants because the transcripts are unstable. Considering the temporal correlation between this event and the onset of r-protein synthesis we suggest that an autogenous control operates at the level of transcript stability. PMID- 4016955 TI - Reconstitution of a developmental clock in vitro: a critical role for astrocytes in the timing of oligodendrocyte differentiation. AB - The rat optic nerve contains three types of macroglial cells: type 1 astrocytes first appear at embryonic day 16 (E16), oligodendrocytes at birth (E21), and type 2 astrocytes between postnatal days 7 and 10. The oligodendrocytes and type 2 astrocytes develop from a common, bipotential O-2A progenitor cell. We show here that although O-2A progenitor cells in E17 optic nerve prematurely stop dividing and differentiate into oligodendrocytes within 2 days in culture, when cultured on a monolayer of type 1 astrocytes, they continue to proliferate; moreover, the first cells differentiate into oligodendrocytes after 4 days in vitro, which is equivalent to the time that oligodendrocytes first appear in vivo. Our findings suggest that the timing of oligodendrocyte differentiation depends on an intrinsic clock in the O-2A progenitor cell that counts cell divisions that are driven by a growth factor (or factors) produced by type 1 astrocytes. PMID- 4016956 TI - Introduction of a selectable gene into primitive stem cells capable of long-term reconstitution of the hemopoietic system of W/Wv mice. AB - We have used the random chromosomal integration sites of retrovirus vectors as unique clonal markers to analyze cell lineage relationships within the hemopoietic stem cell hierarchy. Using a high efficiency protocol for retrovirus mediated gene transfer, anemic W/Wv mutant mice were reconstituted with bone marrow cells infected with a NEO vector. Analysis of the DNA from bone marrow, thymus, and spleen of these reconstituted W/Wv mice indicated insertion of the vector into primitive pluripotent stem cells capable of producing both myeloid and lymphoid progeny as well as into more committed stem cells apparently restricted to either the myeloid or lymphoid lineages. The neo gene was also expressed in these mice, as they contained a variety of G418 resistant in vitro colony-forming cells. These results demonstrate high-efficiency gene transfer and expression in primitive hemopoietic stem cells and provide a direct approach for analyzing the hemopoietic stem cell hierarchy. PMID- 4016957 TI - DNA repeat size in chick embryonic lens epithelium, lens fiber, brain and liver cell nuclei. AB - The DNA repeat size is determined by micrococcal nuclease digestion kinetics and subsequent electrophoresis of the products among various chick embryonic tissues. The repeat size is found to be not significantly different from 193 to 197 bp, for brain and liver at 11 days and for lens epithelium and fiber at different embryonic stages. However, the pattern of micrococcal digestion seems to reveal an overall chromatin modification as a function of development in the lens fibers. PMID- 4016958 TI - Oculopotency of embryonic quail pineals as revealed by cell culture studies. AB - Pineal bodies from 8-day-old quail embryos were dissociated and cultured in order to examine their potency for differentiation under in vitro conditions. Polygonal pigment cells and lentoid bodies started to differentiate after about 2 and 4 weeks, respectively. Lentoid bodies were shown immunologically to contain all classes of crystallins. The results indicate that embryonic pineal cells of avian species retain 'oculopotency' to differentiate into several types of ocular cells. PMID- 4016959 TI - Abstracts of the papers presented at the Tenth International Congress of the International Society of Developmental Biologists, August 4-9, 1985, Los Angeles, California. New discoveries and technologies. PMID- 4016960 TI - Immunization of susceptible BALB/c mice against Leishmania braziliensis. II. Use of temperature-sensitive avirulent clones of parasite for vaccination purposes. AB - Avirulent clones of Leishmania braziliensis were produced by treatment of parental parasite stock with the mutagen N-methyl-N'-methyl-N'-nitro-N nitrosoguanidine and selection for growth at 19 degrees C. These clones have a clear preference for infection and growth in vitro at 19 degrees C rather than the normal 28 degrees C. In addition, they can be used to vaccinate naive mice successfully against growth of the parental parasite clones. Immunity can be adoptively transferred from vaccinated mice by Lyt-1+ cells from immunized animals. PMID- 4016961 TI - Functional analysis of macrophage hybridomas. III. Inhibition of lymphocyte blastogenesis and tumor proliferation. AB - Four cloned macrophage hybridoma cells prepared by fusion of splenic adherent cells with a P388D1 macrophage tumor markedly inhibited the growth of lymphocytes and tumor cells. Macrophage clones 5, 8, 63, and 64 are strong inhibitors of B cell blastogenesis, T-cell blastogenesis, and tumor proliferation, while the P388D1, tumor line and clones 13, 59, and 67 demonstrated little inhibitory activity in all three systems. The inhibitory effect of macrophage hybridomas can be detected within 8 hr, although greater inhibition was noted following longer incubation. The correlations among these three assay systems suggest that similar mechanisms may be involved. The data indicate that the inhibition of cell proliferation was not due to cell lysis. Furthermore, the inhibition of lymphocyte proliferation in Con A-stimulated cultures was not accompanied by inhibition of lymphokine production in the same cultures. Neither prostaglandins nor hydrogen peroxide appear to be primarily responsible for growth inhibition. The inhibitory properties of these macrophage hybridoma lines represent a stable phenotype and provide a homogeneous source of cells for further analysis of the phenomenon. PMID- 4016962 TI - Chronic graft-versus-host disease as a model for scleroderma. II. Mast cell depletion with deposition of immunoglobulins in the skin and fibrosis. AB - We explored the pathologic changes in the skin of mice undergoing a chronic graft versus-host (GVH) reaction. In rodents and in man, chronic GVH includes the deposition of excess collagen in the skin-a reaction which resembles idiopathic scleroderma. GVH disease across minor histocompatibility barriers was produced by injecting B10.D2 cells into irradiated BALB/c mice. These strains are identical at the H-2 and Mls loci but differ in minor histocompatibility antigens. Control BALB/c mice received irradiation and BALB/c cells. Serial skin biopsies were taken and studied for histological changes characteristic of chronic GVHD, for mast cell density, and for the deposition of immunoreactants. GVHD was produced in B10.D2----BALB/c mice as measured by body weight loss and the production of skin changes including dermal fibrosis, loss of fat and appendages, and a mononuclear cell infiltrate. Dermal mast cells, assessed by toluidine blue staining, were normal at Day 11, but had disappeared by Days 21-63 and returned to normal by Day 104. Immunoglobulins IgG, IgA, and IgM appeared at the dermo epidermal junction and along the basement membrane zone of hair follicles. This deposition was maximal at Day 42 and waned thereafter. Thus the appearance of immunoglobulins in the skin was maximal when mast cell staining was minimal. The changes in this GVHD model leading to a scleroderma-like picture in the skin are compatible with an immune etiology for the fibrosis. Vasodilation following liberation of mast cell mediators would facilitate the deposition of immunoglobulins. The disappearance of mast cell staining may be caused by extensive degranulation. We postulate an interaction between GVHD-activated T cells, mast cell stimulation, fibroblast activation, and fibrosis. PMID- 4016963 TI - Differences in the response of non-dividing human diploid fibroblasts (HDF) to inducers of DNA synthesis generated by cycling HDF and HeLa cells. AB - The ability of non-dividing WI-38 cells from different passages to respond to inducers of DNA synthesis generated by other WI-38 cells in G1 or S and HeLa cells in S was studied. The non-dividing cells are refractory to inducers of DNA synthesis generated by WI-38 cells in S but respond to HeLa inducers after a lag period of 3 hours. The WI-38 cells in G1 are not inhibited from entering S in the presence of non-dividing cell nuclei in the heterokaryons. PMID- 4016964 TI - Turnover of nascent proteins in HeLa-S3 cells and the quasi-linear incorporation kinetics of amino acids. AB - The turnover of nascent proteins in HeLa S-3 cells was estimated simultaneously with synthesis by the difference between the expected accumulation of radioactivity, based on rate determinations from very short pulse treatments, from that observed by continuous exposure for 100 min. The results were similar to those from conventional pulse-chase analysis, but not identical for reasons which are discussed. They confirm that extensive protein turnover accompanies synthesis in the growing cell, and therefore net synthesis is much lower than gross synthesis. Cells retained all proteins synthesised during heat treatment at 45 degrees C, indicating the complete inhibition of protein degradation, cells retaining all proteins synthesised. This particular perturbation experimentally validated the deficit method, and its potential usefulness in future turnover studies. PMID- 4016965 TI - Increased replication in plant nuclei, whose spread chromatin contains enlarged nucleosomal linkers, is only partially due to a rise in the number of DNA elongating chains. AB - Dormant and proliferating meristems of Allium cepa L. roots were compared. In vivo DNA synthesis was nine times higher in proliferating meristems, partially due to a 2.5 times increase in the relative number of DNA elongating chains, as estimated after the assay for 3H-TTP incorporation in permeabilized cells. Stereology done on conventional electronmicrographs showed that nucleoplasm was nearly three times larger in nuclei of proliferating meristems, while the amount of compact chromatin did not diminish but redistributed instead, resulting that the chromatin/nucleoplasm interface increased. Finally, the nucleosomal linker as seen after the spreading of the chromatin fibres- was larger and more variable in proliferating than in dormant meristems. PMID- 4016966 TI - Adenylate cyclase of Dictyostelium discoideum: solubilization and Mn2+ dependency. AB - Adenylate cyclase from Dictyostelium discoideum was solubilized under alkaline conditions using the zwitterionic detergent CHAPS. In contrast to the membrane bound adenylate cyclase, the solubilized enzyme can use only Mn2+, but is inactive in the presence of Mg2+. PMID- 4016968 TI - Symposium on rehabilitation of the injured athlete. PMID- 4016967 TI - Effects of spermine on transferrin and iron uptake by reticulocytes: II. Changes in intravesicular pH. AB - An increase in extracellular spermine concentration brought about a progressive rise in intralysosomal pH in rabbit reticulocytes. Since intracellular release of iron from transferrin is believed to involve the protonation of the iron transferrin complex, the rise in intralysomal pH could account for the inhibitory effect of spermine on iron uptake. The inhibition could be reversed if spermine was removed by washing. As a result of spermine treatment, more acid-labile N terminal monoferric transferrin and less apotransferrin were released from the cell. These results are consistant with the protonation theory of iron release. PMID- 4016969 TI - Guidelines for rehabilitation of sports injuries. AB - Rehabilitation involves a functional progression through a systematic program of physical reconditioning involving the re-establishment of intact articulations and muscles, pain-free joints and muscles, joint flexibility, muscular strength, muscular endurance, muscular speed, integrated and coordinated movement (skill patterns), and cardiovascular endurance. Specific demands must be imposed upon the body to bring about redevelopment of each phase. A proper diagnosis prior to beginning, and constant monitoring of the patient's progress during, rehabilitation are necessary so that the demands of the therapeutic regimen can be adjusted according to the patient's progress. The DAPRE technique objectifies isotonic and loaded isometric strength development and therefore stimulates greater strength gains during rehabilitation than other techniques do. PMID- 4016970 TI - Therapeutic exercise. AB - Physical activity provides the biologic stimulus for a number of body adaptive mechanisms and therefore is a potent force in both prevention and treatment of sports injury. It has been shown, however, that therapeutic exercise must be prescribed with precision and care if it is to be of optimal value. There are no "general" effects of exercise. The effects of exercise on the cellular structure of muscle, connective tissue, and the nervous system are specific to the intensity, duration, and frequency of exercise and dependent on the length of time after injury. PMID- 4016971 TI - Braces and taping. AB - Many different types of knee supports are available. Some aid the patient to obtain an early full range of motion and normal strength after injury. Others aid in preventing reinjury. Still others provide the patient with comfort and a feeling of support and serve merely as a reminder to exert caution in sports activity. It is the physician's responsibility to learn the capabilities and limitations of these various devices so that they can be used effectively in his or her practice. PMID- 4016972 TI - Rehabilitation of neck and low back injuries. AB - Sports-related mechanisms of cervical and lumbar spine injury and their clinical presentations have been discussed. The keys to treatment of these injuries in the athlete include rehabilitation of the injured area, recognition of the mechanism of injury, and correction of any technical faults that may have contributed thereto. Criteria for return to sport are a critical part of the rehabilitation of the injured athlete. Most importantly, the practitioner can anticipate potential areas of injury and can recommend prehabilitation exercises to avert many of these injuries. PMID- 4016973 TI - Shoulder rehabilitation. AB - All injuries to the shoulder either directly or indirectly involve the muscles of the shoulder. The involved muscles can easily be identified by examination and rehabilitated utilizing isotonic and isokinetic exercises. The majority of recurring injuries or symptoms following the treatment of a shoulder injury and return to activity are due to either lack of adequate rehabilitation or inappropriate rehabilitation. PMID- 4016974 TI - Rehabilitation of the anterior cruciate deficient knee. AB - Progressive rehabilitation of the anterior cruciate deficient knee requires attention to the signs of recovery or lack of it, so that the rehabilitation program can be adjusted. A close monitoring program by the physician or therapist, or both, is more effective than the introduction of complicated equipment. By dividing the rehabilitation program into segments with specific goals and responsibilities, an informed rehabilitation team (physician, therapist, patient) can progress from injury to complete neuro-musculo-skeletal re-education. PMID- 4016975 TI - Rehabilitation of the ankle. AB - The ankle is the most frequently injured major joint, and ankle sprain is the most frequent sports injury. If the injured ankle is managed correctly from the beginning, pain and swelling and the resultant disability will be kept to a minimum. Early return to participation predisposes the athlete to reinjury. Not only must strength and flexibility be restored, but the athlete must also be pain free and have regained his or her proprioceptive abilities. PMID- 4016976 TI - Psychologic aspects of athletic rehabilitation. AB - Physicians and sports medicine professionals are, by the interpersonal nature of their work, professional communicators. Communication, being multidimensional, requires attentiveness not only to proper outward health practices but also to the internal response of the patient. The format described here and outlined in Table 1 gives a practical model to use, so that as treatment proceeds, patients are influenced at the emotional level with calm, with direction, and with reassurance. Lastly, these guidelines should be used to revise or complement what is already being done. They are not meant to replace a program that is already established. PMID- 4016977 TI - [Immunocomplexes in pregnancy. I. Determination of circulating complexes using the PEG method]. PMID- 4016978 TI - [Cholesterol in the amniotic fluid in the last trimester of pregnancy]. PMID- 4016979 TI - [Total spermagglutinating antibodies and sperm penetration of cervical secretions in infertile women]. PMID- 4016980 TI - [Work activity of women treated for malignant neoplasms of the reproductive organs]. PMID- 4016981 TI - [Chromium in the environment and its relation to human reproduction]. PMID- 4016982 TI - [Levels of cortisol in plasma in the fetus and neonate]. PMID- 4016983 TI - [Microsurgical treatment of female sterility--selection and preparation of patients, peroperative precautions and postoperative care]. PMID- 4016984 TI - [Postcoagulation iatropathology of the cervix uteri]. PMID- 4016985 TI - [Acute pyosalpinx as a sudden acute abdomen]. PMID- 4016986 TI - [Collection of vaginal secretions in girls using a sliding holder]. PMID- 4016987 TI - [Case reports from Cambodia]. PMID- 4016988 TI - [Primary failure of the development of the chorion in chromosome 16 trisomy]. PMID- 4016989 TI - [The receptor for estrogens is not located in the cytoplasm, but in the cell nucleus of the target tissue]. PMID- 4016990 TI - [Blood glycerol levels in pregnant women with a potential glucose tolerance disorder during a stress test. Relation to the birth weight of the fetus]. PMID- 4016991 TI - [The effect of prenatal therapy with corticosteroids on the incidence intranatal fetal hypoxia]. PMID- 4016993 TI - [Sex life of women treated for malignant tumors of the reproductive organs]. PMID- 4016992 TI - [Interstitial pregnancy]. PMID- 4016994 TI - [The most frequent causes of heart failure in pregnancy]. PMID- 4016995 TI - [Pregnancy in adolescence]. PMID- 4016997 TI - [Anemia in the etiology of threatened late abortion and premature labor]. PMID- 4016996 TI - [Actinomycosis of the internal genitalia]. PMID- 4016998 TI - [Bichorionic pregnancy as a cause of posthemorrhagic shock]. PMID- 4016999 TI - [A case of treated primary sterility and the course of pregnancy in the amenorrhea-galactorrhea syndrome associated with pituitary adenoma and hyperprolactinemia]. PMID- 4017000 TI - [An analysis of the causes of congenital defects from the viewpoint of the teratologist]. PMID- 4017001 TI - [Increased doses of clomiphene for ovulation induction]. PMID- 4017002 TI - [The female prostate or Skene's glands and ducts? (Reasons for returning to De Graaf's original term)]. PMID- 4017003 TI - [Immunotherapy of trichomoniasis and the so-called nonspecific colpitis]. PMID- 4017004 TI - [Episiotomy and perineal protection--generally an unnecessary operation and a useless, occasionally risky maneuver?]. PMID- 4017005 TI - [Compulsory confidentiality in heterologous insemination]. PMID- 4017006 TI - [Regulation of food intake in ruminants]. PMID- 4017007 TI - [Measurement of the rectal temperature of rats using a thermoresistor thermometer]. PMID- 4017008 TI - [Evaluation of biological data using nonparametric estimation of the average difference on the TI-59 calculator]. PMID- 4017009 TI - [A labyrinth stimulator using galvanic current, suitable for determining vestibulo-postural relations]. PMID- 4017010 TI - [Identification and classification of proteins in the subretinal fluid. I. Use of specific antisera for differentiating between individual proteins in the subretinal fluid]. PMID- 4017011 TI - [Identification and classification of proteins in subretinal fluid. II. Significance of the electrophoretic analysis of proteins in the subretinal fluid in estimating the duration of retinal detachment and the prognosis for its healing]. PMID- 4017012 TI - [Visual function after surgery of compressive lesions in the area of the anterior intracranial part of the visual pathway]. PMID- 4017013 TI - [Malignant melanoma of the orbit. Case reports]. PMID- 4017014 TI - [The effect of ionizing radiation on the eye. I]. PMID- 4017015 TI - [Uptake of 75Se-selenite by ocular tissue in laboratory rats]. PMID- 4017016 TI - [Pseudoaphakia in childhood]. PMID- 4017017 TI - [Demodex folliculorum]. PMID- 4017018 TI - [The effect of the He-Ne laser on wound healing]. PMID- 4017019 TI - [Changes in the phagocytic activity of neutrophilic leukocytes after irradiation with the He-Ne laser]. PMID- 4017020 TI - [The effect of irradiation with the He-Ne laser on salivary lysozyme]. PMID- 4017021 TI - [A single-phase reconstruction of the tympanic membrane and the auditory ossicles]. PMID- 4017022 TI - [Morphologic changes in extracted colla mallei]. PMID- 4017023 TI - [The effect of the age of miners on the development of occupational hearing loss]. PMID- 4017024 TI - [Craniofacial changes in unilateral aplasia of the ear (radiographic study)]. PMID- 4017025 TI - [Sinusocopy in children and adolescents]. PMID- 4017026 TI - [Tympanometry in childhood]. PMID- 4017027 TI - [Rehabilitation of the voice in patients with Reinke's edema after microsurgical treatment]. PMID- 4017028 TI - [Calcification in the heart. III. Calcification of the myocardium in chronic uremia]. AB - The distribution of calcium deposits in the heart of a patient with chronic uremia was studied by means of x-ray examination [mammography]. The calcification shares features of both dystrophic and metastatic type. It affects predominantly the left ventricular myocardium. PMID- 4017029 TI - [Diagnosis of Alzheimer's disease in the aged. II. Quantitative aspects]. AB - A quantitative aspect was instrumental in the distinction of late Alzheimer's disease from senile brain lesion in 9 cases from a group of 10. Eight to ten plaques in one microscopical field [magnification 400 X] were a decisive finding in Brodmann's area 10 or 21. Neuronal decrease in nucleus basalis was a less reliable feature [7: 10], neuronal frequency in locus coeruleus was the same as in control group. Another criterion seems to be necessary when border line cases of histological Alzheimer's disease with dementia and without dementia are to be distinguished. Subclinical forms of Alzheimer's disease in old age can be supposed because of the finding of plaques in neocortex and neuronal decrease in nucleus basalis in several cases of the control group. PMID- 4017030 TI - [Trichorrhexis nodosa in electron microscopy]. AB - Trichorrhexis nodosa, i. e. a hair fracturing into brush-like widened stumps, was analyzed in an imbecile 4 year-old boy without any sign of aminoaciduria or disturbance of copper metabolism. Scanning electron microscopy showed smoothed hair cuticula with irregular ridges and surface splitting. According to the transmission electron microscopy disintegration of superficial and profound cuticular elements as well was due to progressive development of vacuoles and clefts in amorphous keratin. PMID- 4017031 TI - [A fatal disease of the heart in primary and secondary hemochromatosis]. AB - In a 53 year-old man suffering from idiopathic hemochromatosis a massive myocardial siderosis occurred with disperse necroses and fibroses especially in subepicardial zone of the left ventricle. A similar picture was observed at secondary hemochromatosis in a 33 year-old woman with sideroblastic anemia after repeated blood transfusions. Both patients died of the failure of hypertrophic heart. PMID- 4017032 TI - [Rhabdomyosarcoma in childhood. I. Histologic structure]. AB - Histological structure of rhabdomyosarcoma was studied in a group of 37 children. The classification was: embryonal rhabdomyosarcoma in 28 cases, alveolar rhabdomyosarcoma in 9 cases. 5 cases showed an ambivalent structure. The diagnosis of rhabdomyosarcoma is based on cytology: various rhabdomyoblasts are to be identified as well as distinguished from similar cells. The structural point of view is helpful but diagnostic only in typical cases of sarcoma botryoides and alveolar rhabdomyosarcoma. Undifferentiated cells maturating into rhabdomyoblasts combined with numerous polymorphic cells were found consecutive investigations of individual cases. PMID- 4017033 TI - [Idiopathic inflammatory pseudotumor of the orbit in childhood. II. Biopsy]. AB - Idiopathic inflammatory pseudotumour of the orbit was observed in three children in the age of 5, 8 and 9 years. It was characterized by mixed inflammatory cellularity with prevailing lymphocytes and eosinophilic leucocytes. Cellularity was often perivascular, a concentric lamellar perivascular fibrosis occurred later. Minute necroses of adipose tissue were found in two cases resulting in giant-cell lipogranuloma. Tumorous symptoms receded promptly after administration of corticoids in all cases. PMID- 4017034 TI - [Calcification in the heart. I. Spontaneous coronary embolism due to calcified material]. AB - Thirty-one hearts with advanced calcification of one or both left heart valves were investigated for the presence of spontaneous "calcific" emboli. X-ray (mammography) showed coronary emboli in 14 cases, that is in 45% of the whole series. A total of 265 "calcific" emboli (205 intracoronary and 60 in the left ventricular cavity) was demonstrated. The embolisation occurred most frequently and most extensively in association with postrheumatic mitral valve disease. Coronary "calcific" embolisation must be considered in the differential diagnosis of symptoms of ischemic heart disease in patients suffering from valvular heart lesions. PMID- 4017035 TI - [Calcification in the heart. II. Massive calcification of the myocardium]. AB - A case is presented of a 19-year-old African with massive coarse nodular calcification affecting selectively the left heart myocardium. The calcification is dystrophic in nature and its cause is unknown. There are only 4 similar cases described in the literature. PMID- 4017036 TI - [Psychophysiology and its methodology]. PMID- 4017037 TI - [The development and significance of synkinetic segmental hypermotility of the cervical vertebrae in the sagittal plane]. PMID- 4017038 TI - [The level and laterality of synkinetic segmental hypermotility of vertebrae in the sagittal plane]. PMID- 4017039 TI - [Use of the F wave in clinical electromyography]. PMID- 4017040 TI - [Electrophoresis of proteins in cerebrospinal fluid and blood on thin-layer agarose. Methods and normal values]. PMID- 4017041 TI - [Comparison of the electrophoresis of proteins in the cerebrospinal fluid and blood on thin-layer agarose and on paper]. PMID- 4017042 TI - [Multifocal cerebral, meningeal and subcutaneous cysticercosis]. PMID- 4017043 TI - [Herpetic encephalitis]. PMID- 4017044 TI - [An unusual case of self-mutilation]. PMID- 4017045 TI - [A case of agranulocytosis during treatment with thioridazine]. PMID- 4017046 TI - [International classification of diseases from the aspect of pediatric and adolescent psychiatry]. PMID- 4017047 TI - [The legal importance of the citizen's will in the modern development of mental health care]. PMID- 4017048 TI - [An attempt to integrate and complete information about patients and to simplify work with medical records]. PMID- 4017049 TI - [Somatic diseases in patients in psychiatric facilities]. PMID- 4017050 TI - [Malignant neuroleptic syndrome]. PMID- 4017051 TI - [Behavior pattern in the secondary prevention of myocardial infarct]. PMID- 4017052 TI - [Idealogic basis of postgraduate work in Czechoslovak psychiatry]. PMID- 4017053 TI - [The therapeutic and management roles of psychiatry]. PMID- 4017054 TI - [Postgraduate preparation of psychiatrists for work in ambulatory care]. PMID- 4017055 TI - [The role of clinical psychology in adult psychiatry]. PMID- 4017056 TI - [Experience with radiotherapy in therapeutically resistant schizophrenia]. PMID- 4017057 TI - [Rehabilitation therapy as a part of comprehensive psychiatric care in a clinical setting]. PMID- 4017058 TI - [Evaluation of the record of the questioning of the accused and the witness by an expert psychiatrist]. PMID- 4017059 TI - [Do "sexually immature" pedophilic delinquents differ from pedophiles?]. PMID- 4017060 TI - [Clinical experience in the diagnosis and treatment of sarcoidosis in children and adolescents]. PMID- 4017061 TI - [Levels of blood lipids and blood pressure in children in families with a history of cardiovascular disease. II]. PMID- 4017062 TI - [NK cells in children]. PMID- 4017063 TI - [Atypical Guillain-Barre syndromes in childhood]. PMID- 4017064 TI - [Cardiac disease in chronic juvenile arthritis]. PMID- 4017065 TI - [Treatment of gynecomastia with oxymetholone and its excretion in urine]. PMID- 4017066 TI - [Differential diagnosis of hematuria and proteinuria in childhood]. PMID- 4017068 TI - [Analysis of the work of the district pediatrician in nurseries]. PMID- 4017067 TI - [Analysis of mycoflora in dehydrated semolina for children]. PMID- 4017070 TI - [The importance of proper footwear in children]. PMID- 4017069 TI - [Vesico-ureteral reflux in celiac disease]. PMID- 4017071 TI - [Prevention of errors in ambulatory pediatric practice]. PMID- 4017072 TI - [Child care in Hungary. I]. PMID- 4017073 TI - [Child care in the Gyor-Sopron District. II]. PMID- 4017074 TI - [Osseous complications after BCG vaccination]. PMID- 4017075 TI - [Pulmonary function as an indicator of lung growth in patients with pituitary nanism]. PMID- 4017076 TI - [Antibodies to gluten in children with celiac sprue determined by the ELISA method]. PMID- 4017077 TI - [Metabolic defects in children with fetal hydantoin syndrome]. PMID- 4017078 TI - [Stress fractures of the tibia in children]. PMID- 4017079 TI - [Metachromatic leukodystrophy with a familial incidence; prenatal diagnosis]. PMID- 4017080 TI - [Vascular malformations imitating a patent ductus arteriosus]. PMID- 4017081 TI - [Use of immunology in pediatric neurology]. PMID- 4017082 TI - [Possibilities of improving ambulatory care of children with chronic diseases]. PMID- 4017083 TI - [Flatfoot in children]. PMID- 4017085 TI - [The functioning of the family from the viewpoint of the pediatrician and social worker]. PMID- 4017084 TI - [An iatrogenic cause of a foreign body in the blood circulation]. PMID- 4017086 TI - [Changes in pulmonary hemodynamics in children with congenital heart defects and left-right shunts]. PMID- 4017087 TI - [Long-term study of neonates at risk and neonates in a control group. III. Changes in the social conditions of the families of the studied group of children from ages 1 to 3]. PMID- 4017088 TI - [Blood cholesterol in adolescents]. PMID- 4017089 TI - [The significance of the composition of concretions in juvenile urolithiasis]. PMID- 4017090 TI - [Transfer factor in the treatment of children with disorders of cellular immunity]. PMID- 4017091 TI - [Natural killers--NK cells--in the fetus and neonate]. PMID- 4017092 TI - [The syndrome of sudden and unexpected infant death (SID)]. PMID- 4017094 TI - [Development of socio-medical aspects in medical activity]. PMID- 4017093 TI - [Genetic counseling in planned and existing homogamy]. PMID- 4017095 TI - [The aged person in the care of the community physician]. PMID- 4017096 TI - [Characteristics of personal and family conditions of persons in early old age in an urban population]. PMID- 4017097 TI - [Non-institutional care of the aged]. PMID- 4017098 TI - [Regional differences in drug utilization]. PMID- 4017099 TI - [The division of tasks, documentation and records in dispensary care]. PMID- 4017100 TI - [Meetings of administrators as a part of the AIS (Automated Information System) of the OUNZ (District Institute of National Health)]. PMID- 4017101 TI - Phosphate buffer and salt medium concentrations affect the inactivation of T4 phage by platinum(II) complexes. AB - The initial rate of inactivation of T4 phage by solutions of [Pt(NH3)2Cl2], [PtenCl2] and [Pten(H2O)2] (NO3)2 at fixed values of pH is strongly reduced by phosphate buffer, slightly reduced by acetate buffer and apparently not influenced by bis(2-hydroxyethyl)aminotris(hydroxymethyl)methane (BIS-Tris) buffer and HEPES buffer. The phosphate abolishes the antiphage activity of the platinum complexes probably by some sort of complex formation. This together with dimerization reactions qualitatively explains the tailing off of the phage inactivation rate. High concentrations of NaNO3 as the salt medium give increased phage inactivation rates, which are also strongly pH-dependent. PMID- 4017102 TI - Heteroassociation of O- and N-isopropyl derivatives of barbital and phenobarbital with 9-ethyladenine. AB - Heteroassociation of O- and N-isopropyl derivatives of barbital and phenobarbital with 9-ethyladenine (9-EA) in CCl4 solutions were studied by infrared spectroscopy. Cyclic heterodimers of high stability (725 less than KH less than 1960 1 X mol-1) compared to the corresponding homodimers (20 less than KD less than 60 1 X mol-1) were formed. The heteroassociation constants are interpreted in terms of both the hydrogen bonding tendency of the donor and acceptor centres and the number of sites available for the formation of hydrogen bonds. Such measurements may contribute to the understanding of the interactions between barbiturates, adenosine and their receptors in the brain. PMID- 4017103 TI - Structure/activity studies of the nephrotoxic and mutagenic action of cysteine conjugates of chloro- and fluoroalkenes. AB - The cysteine conjugates of the nephrotoxins hexachlorobutadiene (HCBD), tetrafluoroethylene (TFE) and hexafluoropropene (HFP), together with those of trichloroethylene and perchloroethylene, have been chemically synthesized and a relationship determined between their structures and their nephrotoxicity and mutagenicity in vitro. All of the conjugates had a marked effect on the uptake of both the organic anion p-aminohippuric acid (PAH) and the cation tetraethylammonium bromide (TEA) into rat kidney slices, suggesting activation of the conjugates in the slices to a toxic species which interferes with ion transport. This observation is consistent with the known nephrotoxicity of HCBD, TFE and HFP in vivo. Each of the conjugates was found to be metabolised by rat kidney slices and by semi-purified rat kidney beta-lyase to pyruvate, ammonia and an unidentified reactive metabolite. When semi-purified beta-lyase was used stoichiometric amounts of pyruvate and ammonia were produced. Although all of the conjugates were activated by beta-lyase and had a similar effect on ion transport their mutagenicity differed markedly. The conjugates of HCBD, trichloroethylene and perchloroethylene were mutagenic in the Ames bacterial mutation assay when activated by rat kidney S9. Metabolic cofactors were not required suggesting that activation was due to the enzyme beta-lyase. In the same assay the conjugates of TFE and HFP were not mutagenic either in the presence or absence of rat kidney S9 and cofactors. With a limited number of cysteine conjugates a clear distinction has been identified between the conjugates of chloroalkenes which were were similarly nephrotoxic but were not mutagenic. The mutagenicity of the cysteine conjugate of HCBD is consistent with the known renal carcinogenicity of this chemical. PMID- 4017104 TI - Characterization and measurement of metallothionein messenger RNA of C57BL mouse liver. AB - Liver poly(A)+RNA of Cd2+-treated C57BL mouse was characterized by cell-free translation, particularly intending to establish a procedure to measure the levels of messenger RNA coding for metallothioneins (MT-mRNA). Intact polysomes were obtained by Mg2+ precipitation from the liver cytoplasm of mice injected with 1 mg Cd2+/kg body wt. Poly(A)+RNA isolated from the polysomes was translated by a wheat germ cell-free system and the [35S]cysteine-labeled translation products were analyzed by sodium dodecyl sulfate (SDS)-15% polyacrylamide gel electrophoresis and fluorography. MTs were identified in the translation products directed by the RNA from the Cd2+-treated mice, but not in the translation products directed by the RNA from untreated mice. Relative incorporation of [35S]cysteine into MTs was determined by densitometrical quantification of the MT bands, and was found to be linear up to a RNA concentration of 150 micrograms/ml in the translation reaction mixture, showing that this system is suitable for the measurement of translatable MT-mRNA levels. Cd2+ stimulated the total levels of cell-free translation (1.4-fold at 20-60 micrograms/ml), not specifically to MT mRNA. MT-mRNA sedimented at 9S in a sucrose gradient, and its size was comparable with rat and human MT-mRNAs. PMID- 4017105 TI - In vivo covalent binding of retronecine-labelled [3H]seneciphylline and [3H]senecionine to DNA of rat liver, lung and kidney. AB - Retronecine-labelled [3H]seneciphylline ([3H]SPH) and [3H]senecionine ([3H]SON) of high specific radioactivity (22 and 49 mCi/mmol, respectively) were prepared biosynthetically with seedlings of Senecio vulgaris L. using [2,3-3H]putrescine as precursor. [2,3-3H]Putrescine was synthesized by Gabriel synthesis of 1,4 diamino-2-butene from 1,4-dibromo-2-butene and catalytic hydrogenation of the product with tritium gas. Rats of both sexes were treated with the labelled pyrrolizidine alkaloids (PAs) (75-215 microCi SPH or 40-485 microCi SON/kg body wt.) and killed after 6 h or 4-5 days. SON-treated females excreted 83.4 +/- 0.2% of applied radioactivity in faeces and urine within 4 days whereas equally treated males excreted 90.9 +/- 3.2% in the same time. Excretion of 3H-activity from SPH-treated females was completed within 5 days (104.7 +/- 6.4%). Corresponding with these results, tissue levels were highest in SON-treated females. DNA and proteins were isolated from liver, lungs and kidneys and covalent binding of the alkaloids to DNA was determined. A Covalent Binding Index (CBI, mumol alkaloid bound per mol nucleotides/mmol alkaloid administered per kg body wt.) of 210 +/- 12 was found for the liver from SON-treated females whereas binding to liver DNA of males was lower by a factor of 4. The DNA damage determined six hours after treatment persisted during the following 4 days. Administration of [3H]SPH to female and male rats resulted in a CBI of 69 +/- 7 and 73/92, respectively, for the liver DNA. Furthermore we found binding of both alkaloids to DNA of lungs and kidneys in male and female rats. The in vivo formation of [3H]SON derived DNA adducts could be proved by HPLC analysis of hydrolyzed DNA. PMID- 4017106 TI - Specificity in carcinogen-DNA interaction: a theoretical exploration of the factors involved in the effect of neighboring bases on N-methyl-N-nitrosourea alkylation of DNA. AB - Recent experimental studies indicate that in a polynucleotide chain neighboring bases have a significant effect on the relative alkylation of O6 or N7 of guanine by N-methyl-N-nitrosourea (MNU). This paper provides a theoretical exploration of this phenomenon in terms of an appropriate index of reactivity, called accessible surface integrated field (ASIF), introduced recently for the very sake of accounting for specificity or selectivity in drug-macromolecule interaction. The detailed analysis indicates that in the present case the observed variations in relative reactivity are attributable essentially to parallel variations in the accessibilities to the target atoms. PMID- 4017107 TI - Fe2+-supported in vivo lipid peroxidation induced by compounds undergoing redox cycling. AB - Treatment of male mice with the redox cycling compounds nitrofurantoin, paraquat, diquat or menadione failed to elicit in vivo lipid peroxidation as evidenced by ethane exhalation. The first three led to an enhanced ethane production, however, when the animals were pretreated with a low dose of Fe2+. While GSH-depletion by phorone pretreatment alone had no influence on the in vivo lipid peroxidation as evidenced by ethane expiration in the presence of either compound, the combined treatment with phorone, Fe2+ and nitrofurantoin, paraquat or diquat led to a further enhancement of ethane exhalation. These results indicate that redox cycling compounds do not initiate lipid peroxidation by themselves, but are well capable of stimulating the iron-induced LPO. PMID- 4017108 TI - Studies on the constituents of medicinal and related plants in Sri Lanka. II. Isolation and structures of new gamma-pyrone and related compounds from Hypericum mysorense Heyne. PMID- 4017109 TI - An enantioselective synthesis of platelet-activating factors, their enantiomers, and their analogues from D- and L-tartaric acids. PMID- 4017110 TI - A new macrocyclic hexaamine ligand for the dissolution of human inorganic calculi. PMID- 4017111 TI - A new fluorometric method for latamoxef in biological materials using 2,6-diamino 3-nitrosopyridine. PMID- 4017112 TI - Heterobifunctional reagents for cross-linking of sugar with protein. PMID- 4017113 TI - Specific antiserum to 2-hydroxyestradiol 17-sulfate (clinical analysis on steroids. XXX). PMID- 4017114 TI - Studies on high-performance liquid chromatography with electrochemical detection. The pH-dependency of enzymic sulfation of catechol estrogens. PMID- 4017115 TI - The biological actions of deoxypodophyllotoxin (anthricin). I. Physiological activities and conformational analysis of deoxypodophyllotoxin. PMID- 4017116 TI - Selectivity and efficiency of utilization of galactosyl-oligosaccharides by bifidobacteria. PMID- 4017117 TI - Mechanism of action of rhatannin on plasma amino acid levels in rats. PMID- 4017118 TI - Hyperlipemia-improving effects of ginsenoside-Rb2 in cholesterol-fed rats. PMID- 4017119 TI - Inhibition of sialyltransferases of murine lymphocytes by disaccharide nucleosides. PMID- 4017120 TI - Rectal absorption of [Asu1,7]-eel calcitonin in rats. PMID- 4017121 TI - Application of synthetic alkyl glycoside vesicles as drug carriers. I. Preparation and physical properties. PMID- 4017122 TI - Effect of chloride ions on the interaction between salicylic acid and human serum albumin studied by frontal affinity chromatography. PMID- 4017123 TI - Recirculatory moment analysis of drugs in man: estimation of extraction ratio and mean cycle time for single systemic and pulmonary circulation. PMID- 4017124 TI - Effect of crystallinity on the percutaneous absorption of corticosteroid. I. Determination of the degree of crystallinity of hydrocortisone acetate in ground mixtures with crystalline cellulose. PMID- 4017125 TI - Effect of tabletting on the degree of crystallinity and on the dehydration and decomposition points of cephalexin crystalline powder. PMID- 4017126 TI - Effects of neurotropin on rat liver microsomes and lysosomes, and in vitro lipid peroxidation. PMID- 4017127 TI - Structure-activity relationship of 3- and 4-acyloxy-1-(1,3-dioxolan-4 ylmethyl)piperidine derivatives. PMID- 4017128 TI - Preparation of specific antisera to 3 beta-hydroxy-5-cholenoic acid by immunization with conjugates attached to protein through the C-3 position. PMID- 4017129 TI - Uracil derivatives. V. Syntheses and growth-inhibitory activity against L-1210 cells of 5-substituted 2'-deoxyuridines and orotidine derivatives. PMID- 4017130 TI - Studies on the mechanism of the hypoglycemic activity of ginsenoside-Rb2 in streptozotocin-diabetic rats. PMID- 4017131 TI - Synthesis and adjuvant activity of FK-156 analogues: acyl derivatives of N-[N2-(L alanyl-gamma-D-glutamyl)-2(L),2'(D)-diamino-1-pimeloyl ]glycine. PMID- 4017132 TI - Mixing of single-chain amphiphiles in two-chain lipid bilayers. 2. Characteristics of chlorophyll a and alpha-tocopherol incorporation in unilamellar phosphatidylcholine vesicles. AB - As a step toward the elucidation of the biological significance of the isoprenic chains found ubiquitously in single-chain lipids involved in electron and energy transfer of chloroplasts and mitochondria, we undertook a comparative study of the incorporation of chlorophyll a (Chl a) and alpha-tocopherol (alpha T) in unilamellar phosphatidylcholine (PC) vesicles. We observed that while Chl alpha is added to the PC bilayers in a simple, almost linear way, the inclusion of alpha T is a sigmoid-like function characterized first by a slow variation of alpha T incorporation followed by a rather steep increase till saturation occurs at initial mol% alpha T of approx. 5%. Owing to the likeness of the isoprenic chains of Chl a and alpha T the simplest interpretation of the data is that the different mixing behaviours of the two lipids in PC vesicles are due to the special arrangement of the tetrapyrrole macrocycle and the chromanol ring in the lipid bilayers. However, no satisfactory explanation of the mechanisms involved can be given as yet. One possibility is that the inclusion of Chl a and alpha T in the membranes results from adsorption differences brought about by the extent of penetration of the molecule into the monolayers of the unilamellar vesicles. PMID- 4017133 TI - Analysis of gangliosides using fast atom bombardment mass spectrometry. AB - The native gangliosides GM3, GM1, Fuc-GM1, GD1a, GD1b, Fuc-GD1b, GT1b and GQ1b were analysed by fast atom bombardment mass spectrometry (FAB-MS) in the negative ion mode in a matrix of thioglycerol. After permethylation the same gangliosides were analysed by electron impact (EI) and FAB-MS in the positive ion mode. The negative ion mass spectra furnished information on the molecular weight, the ceramide moiety and the sequence of carbohydrate residues. The sites of attachment and the number of sialic acids present could be deduced directly from the pattern of sequence ions. After addition of sodium acetate positive ion FAB spectra of the permethylated samples show intense pseudomolecular ions M + Na, that provide evidence on the homogeneity of the samples. In addition, the ceramide part, the oligosaccharide moiety obtained after cleavage of the glycosidic bond of the hexosamine residue, the whole carbohydrate chain and the sialic acids are represented by specific fragment ions. With EI-MS further information can be obtained on the sphingosine and fatty acid components of the ceramide residue. The data show, that the combination of soft ionization mass spectrometry with classical EI-MS gives valuable information on the structure and homogeneity of gangliosides. The method is also applicable to the structural elucidation or quantitation of more complex gangliosides or glycolipid mixtures using only micrograms of material. PMID- 4017134 TI - Glycolipids from Nocardia rhodochrous grown on glucose. AB - Nocardia rhodochrous grown on glucose-supplemented medium produced a high yield of a glycolipid fraction (m.p. 65-70 degrees C and [alpha]25D = + 31.4 degrees), identified as 6-(C40-C46) nocardomycoloylglucose. It accounted for approx. 3.4% of the cell dry wt. and 41% of the diethyl ether soluble lipids obtained from ethanol-diethyl ether extract. Dimycoloyltrehalose (cord factor) was found in a very small amount (0.11%). PMID- 4017135 TI - Lipid-specific fluorescent probes in studies of biological membranes. AB - Lipid-specific fluorescent probes are natural lipids carrying an apolar fluorophore in one of the hydrocarbon chains. Since such probes retain the head groups and resemble the molecular shape of native membrane lipids, they largely mimic the behaviour of their natural prototypes in biological membranes. Information provided by the lipid-specific probes is more differentiated and easier to interpret than that obtained from non-lipid probes. The principles of design of lipid-specific probes are formulated and the relative advantages and disadvantages of various fluorophores are discussed. In order to reduce ambiguities caused by perturbation of the probe environment, it is proposed to use, in a comparative manner, two or more lipid-specific probes resembling each other in all aspects except the polar head groups (the 'two probes' concept). Two types of fluorophores, the anthrylvinyl group and the perylenoyl group, were found to be well suited for the synthesis of lipid-specific probes. Use of both types of probes 'in tandem' opens new possibilities for studying lipid-protein and lipid-lipid interactions in biological membranes. The anthrylvinyl- and perylenoyl-labeled lipids were applied in studies of serum lipoproteins and erythrocyte membranes. A new highly sensitive ligand-receptor binding assay and a new approach to biological signal amplifying based on the use of lipid-specific probes are described. PMID- 4017137 TI - [The story of oxygen (2)]. AB - The authors, in this second part of the oxygen story, resolutely cross the borders of the biophysical field, and face the origins and becoming of life, the stages of which are synthesized in "casket" terms, unusual for surgeons: "protobionts", "procariots", "cyanobacteria", "chlorophyll", "caroteonides", "fermentation", "anaerobic glycolysis", "eucariots", "respiratory chain", "mitocondria". This is not an unconventional biological exercise, but the effort to give clinics a more legible ground, a sort of common denominator of the most different pathologies, and, among these ones, at the first place, just those of the specialistic branch, also less frequenter of biology, that is, surgery. This common denominator, the oxygen radicals represent the emerging apex of, like the peak of an iceberg, in fact, can be only investigated through an exasperated "philogenetic" recovering. Such process of "archaeology" seems to be the only suitable to supply us the cipher-key of the ambiguous, shifty character of oxygen, and entrust us with a cultural patrimony being unique as it is spendable in an immediate clinical future. PMID- 4017136 TI - [Technic of multiple procurement from donor cadavers (observations on 19 cases)]. AB - Several procedures for multiple cadaveric organ procurement have been developed for the recent growth of transplantation of extrarenal organs. These techniques permit removal of the kidneys, liver, pancreas and heart from the same donor without jeopardy to the kidneys above all. At the Department of Surgery - Section Transplantation of the University of Genoa in 1983 and 1984 19 multiple organ harvesting have been carried out. The kidneys were transplanted at our Center or at other Nit Center. Two patients received segmental pancreatic allograft. Two livers were sent to other Italian and European Centers and successfully transplanted. PMID- 4017138 TI - Effects of meal viscosity on serum gastrin response and gastric emptying rate in duodenal ulcer patients. AB - Addition of guar gum to a meal increases its viscosity. Two test meals of differing viscosities were eaten by 15 duodenal ulcer patients. Gastric emptying rates were measured over 120 minute periods after ingestion of the meals by determining the intragastric content of the polyethylene glycol which had been included in the meals. Serum gastrin levels were determined over the same period by radioimmunoassay. The gastric emptying rate was significantly (p less than 0.05) lower after the meal of higher viscosity, but there were no significant differences in serum gastrin levels at any time of measurement after the two meals. PMID- 4017139 TI - [A case of duodenal duplication in the adult]. AB - The authors describe a rare case of duodenal duplication presenting in adult life; the complete preoperative investigations did not substantiate. The diagnosis which can be accomplished in most cases only intraoperatively. The diagnosis is mainly based upon knowledge of the condition and upon pathologic examination. PMID- 4017140 TI - [Cystic lymphangioma: etiopathogenetic and diagnostic considerations apropos of 2 cases]. AB - The authors show two cases of cystic lymphangioma, one located at the neck, the other in the inguinal region, both arising in aged patients. From the study of such cases, the Authors start for studying the etiopathogenetic and histologic aspects, dwell upon the clinics and diagnosis of such neoplasms, and indicate as the sole radical treatment the surgical extirpation. PMID- 4017141 TI - [Partial paralysis of the right lumbar plexus caused by a traumatic hematoma of the ileo-psoas muscle]. AB - The authors show a case of paralysis of right femoral nerve, subsequent to extrinsic compression due to traumatic hematoma of ileo-psoas muscle. What emerges from the revitwing of the international literature, as well as from the personal experience is both a complete nosographic framing and the necessity for an early surgical intervention. PMID- 4017142 TI - [Acute appendicitis: clinico-diagnostic and therapeutic considerations]. AB - Since january 1970-december 1982, 58 patients underwent emergently appendectomy for acute appendicitis. 31 (53,4 percent) where males; the average age was 21 +/- 2,3 years (M +/- SEM). The duration of symptoms ranged from 1-6 hours (10,3 percent of cases) to over 48 hours, before the hospital admission (15,4 percent of cases). 27 patients (46,5 percent) had a clinical examination at home by a physician. 21 patients (36,4 percent) came to hospital emergency unit without previous physical examination; 10 (17,2 percent) were transferred from other departments. In 6,9 percent of cases was present a perforated appendicitis with peritonitis. During operation, in 50 percent of patients was performed a therapeutic peritoneal lavage. In 63,7 percent of cases multiple drains were placed in peritoneal cavity. In all patients was effected postoperative antibiotic profilaxis. The mortality rate was 3,4 percent. General complications were observed more in patients with perforated appendicitis. This review suggests the following remarcable data: morbidity of this disease is still high; the physical examination is more important than laboratory work (especially in the elderly patients, which are often immunodepressed and in children, with leucocitosis-lack at hospital admission); early surgery is the most important factor to the improvement of prognosis in these cases and the results of surgical treatment are improved by large vertical incisions, peritoneal lavage and application of multiple intracavitary drains. PMID- 4017143 TI - [Uterine multiple node fibromyomatosis associated with an asymptomatic leiomyoma of the small intestine]. AB - Benign small bowel tumours are rare, often asymptomatic and are founded incidentally at surgery or post mortem examination. In about 70% patients with benign small bowel tumour were reported to have associated benign or malignant tumours of other districts. The Authors report a case of leiomyoma of the small intestine associated with multinodular leiofibromyomatosis of the uterus. PMID- 4017144 TI - [Thalamic fractures of the calcaneus. Indications and osteosynthesis technics]. AB - The authors describe their therapeutical attitude as regards the thalamic fractures of heel, and distinguish two basic methods of surgical approach: reducing of thalamus and synthesis with only screws in the simple fractures; reducing of thalamus and restoration of the heel morphology by mtans of plate and screws in the complex fractures. They particularly report the satisfactory results got through the use of Lanzetta's plates, which, allowing a good reducting and a steady synthesis in the complex fractures also, permit an early mobilization. PMID- 4017145 TI - [Traumatic simultaneous bilateral fracture of the first rib]. AB - The authors report a very rare case of traumatic simultaneous bilateral fracture of lrst rib with no concomitant lesions of skeleton, internal organs, or vasculo nervous ones. PMID- 4017146 TI - [Evaluation of the aftermath of trimalleolar fractures of the tibio-tarsal joint]. AB - The authors have examined the follow-up of 57 cases of trimalleolar fractures treated by internal fixation. Statistics show a good end result. The Authors, moreover, report the frequent presence of synostosis tibio-fibulare distale. This condition, however, has no influence on ankle motion. PMID- 4017147 TI - [Evaluation of the results of the surgical treatment of hernias of the lumbar disk]. AB - The authors present their casuistry about surgical treatment of the herniated lumbar disc, operated during the period from 1979-1983, underling the utility of the operating field without blood, obtainable with particulare prone position of the patient, also called "egg position", with controlled hypotension, which allow a complete vision without wide hemilaminectomie. PMID- 4017148 TI - [A case of extensor indicis brevis manus muscle]. AB - The authors present one case of extensor indicis brevis muscle discovered accidentally during surgical operation for suspected synovial cyst of the left hand. They underlin the rarity and the facility of wrong diagnosis in the presence of such anomalous muscle. PMID- 4017149 TI - [Surgical treatment of humeral epicondylitis]. AB - The authors show the remote reviewing of 41 patients suffering from tenuis elbow, surgically treated from 1975 up to 1983. The results at the checking appear excellent in 67,4%, good in 20,9%, sufficient in 9,4% and, at last, poor in 2,3%. PMID- 4017150 TI - [Osteochondritis dissecans: a rare localization]. AB - The authors show a non-frequent location of osteochondritis, occasionally diagnosed owing to a trauma. In consideration of the practically inexistent painful symptomatology, no specific therapy was performed. The clinical and radiographic checking was effected after eight months. PMID- 4017151 TI - [Frieberg-Kohler disease. Long-term review of the surgical treatment in 20 cases]. AB - The authors show the reviewing of twenty patients suffering from Frieberg Kohler's disease, surgically treated from 1975 up to 1980. The surgical intervention had been suggested by the important painful symptomatology, resisting to the conservative therapy. At checking, the patients were all satisfied with the results of operation, and could start again with their usual job. PMID- 4017152 TI - Ventilation thresholds may be misinterpreted with the presentation of mean data. AB - Past research has used either individual or mean data to illustrate the determination of the ventilation thresholds. Although an individual's data may represent the best rather than the typical response, the accuracy and validity of threshold determinations can be assessed. In contrast, the presentation of mean data may not allow the reader to evaluate the internal validity of the results. PMID- 4017153 TI - Force analysis of the rowing stroke employing two differing oar grips. AB - The velocity of the rowing boat appears to depend on the force which the athlete applies at the handle of the oar. Although force is generated by legs, upper body, and arms, the latter are the only limbs which actually transmit and apply the force against the oar. The force output of the arms seem to be a function of the forearm position used by the athlete while gripping the oar. The traditional gripping technique is with the forearms in pronation. This technique was never challenged or scientifically researched to see whatever a modified one might lead to better efficiency. Consequently, the purpose of this investigation was to analyze whether athletes' force output differed if the gripping technique was changed from pronation to a semiprone grip (one arm prone, the other semiprone). Under the specific conditions of this investigation it was demonstrated that the semiprone position was generating greater force output, thus being superior to the classical prone grip. PMID- 4017154 TI - Alterations in head dynamics with the addition of a hockey helmet and face shield under inertial loading. AB - The effect of a hockey helmet and face shield on the head and neck during inertial loading was studied. A Hybrid III Anthropometric Test Dummy (ATD) was struck from both the front and rear by a spring-loaded, instrumented striker moving at 2.9 ms-1. Data were collected from a triaxial force transducer mounted at the atlanto-occipital (a-o) junction of the ATD, a load cell in the striker, and by cinematography (250 fps). Angular kinematics of the head and moments of force about the a-o junction were determined along with impact force levels. When compared to a bare-head condition, the addition of a helmet and face shield caused an increase in head angular displacement (20-40%) but did not affect head angular acceleration. Axial and shear forces at the a-o junction did not change appreciably with the addition of a helmet and face shield. A triphasic pattern was evident for the neck moments including a small phase which represented a seating of the headform on the nodding blocks of the uppermost ATD neck segment, and two larger phases of opposite polarity which represented the motion of the head relative to the trunk during the first 350 ms after impact. No substantial differences were apparent between the helmeted and non-helmeted trials. The magnitudes of forces and moments found in the present study were well within tolerance levels reported by others (Melvin, 1979; Cheng et al., 1982). It was concluded that the increase in angular displacement of the head, with the addition of a helmet and face shield, does not place the wearer in a position of increased risk of cervical spine trauma. PMID- 4017155 TI - Age specific prediction of maximal oxygen uptake in boys. AB - Maximal oxygen uptake was determined in 62 boys each year from age 11 to 15 years. Multiple regression analyses were used to predict treadmill VO2 max at yearly age intervals from size measures and submaximal cycle heart rates. Derived equations were validated in an independent sample of 98 boys of the same age range. In boys aged 12 to 15 years approximately 80% or more of the variance in VO2 max was accounted for by age specific equations employing mass, height and skinfolds as explanatory variables. Prediction of VO2max was not as strong for 10 and 11 year olds, with less than 70% of the variance explained. Measures of VO2 or work rate and heart rate were not useful in predicting VO2max either by themselves or in conjunction with the size measures. The findings clearly demonstrated that submaximal exercise testing to predict VO2max, or cardiorespiratory fitness, in boys was of questionable value. The prediction of VO2max in boys aged 12 to 15 by in the independent sample was shown to have a mean absolute error of 6 to 8% while the value for age 11 y was 10%. The error is similar in magnitude to that of predicting VO2max with an exercise test in adults. The present age specific equations resulted in smaller errors of estimation than found in previous studies of VO2max estimation in children. PMID- 4017156 TI - Submaximal endurance performance related to the ventilation thresholds. AB - This study was undertaken to compare the variance in time to fatigue (TF) at intensities expressed relative to VO2max, ventilation threshold 1 (VT1) or 2 (VT2). Two 3-min, 30 Watt incremental tests on the cycle ergometer were used to determine VO2max (50.7 +/- 7.2 ml X kg-1 X min-1), VT1 (51.7 +/- 3.7% VO2max) and VT2 (79.0 +/- 3.7% VO2max) for 16 subjects. At weekly intervals, subjects worked to volitional fatigue at 3 randomly-ordered power outputs that represented 73.1 +/- 2.8, 85.4 +/- 2.8 and 95.0 +/- 3.4% VO2max. A significant quadratic interaction was observed for TF values between VO2max and intensity, suggesting a different magnitude of response related to VO2max. Subject data were then grouped according to VO2max into a low (N = 5, 40-44 ml X kg-1 X min-1), medium (N = 5, 48-52 ml X kg-1 X min-1) or high (N = 6, 56-61 ml X kg-1 X min-1) category. For all groups, a decaying exponential function best described the relationship between TF and intensity. The method of expressing intensity appeared to have only a small effect on the proportion of variance explained by this logarithmic relationship (0.85 less than or equal to r2 less than or equal to 0.93). In contrast, however, a 30% reduction in the standard error of estimate for TF was observed when intensity was expressed relative to both ventilation thresholds as compared to the traditional expression of intensity relative to VO2max.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4017157 TI - Accuracy of residual volume prediction--effects on body composition estimation in pulmonary dysfunction. AB - The accuracy of predicting residual volume (RV) and the effect of employing such predictions in the assessment of body composition by hydrostatic weighing was examined. Prediction equations derived by Wilmore (Med. Sci. Sports, 1969) and Boren et al. (Am. J. Med., 1966) were cross-validated on 400 male subjects with varying degrees of pulmonary dysfunction. Statistical analysis included comparison of predicted vs measured RV and regression analysis of measured on predicted values. Neither equation met acceptable statistical criteria (p greater than .05). Underwater weights were calculated based upon the measured RV and an assumed standard body weight, body density, and percent body fat (i.e., 70 kg, 1.0647 g/cc and 15.0%). Predicted RV was then substituted in the calculation and the effect on standardized values examined, between the calculated and standardized percent fat value with both equations. Results suggest in the present subjects, RV cannot be accurately predicted and the use of such prediction equations introduces sizable errors in body composition estimation. PMID- 4017158 TI - Normalizing the performances of athletes in Olympic weightlifting. AB - A method of comparing the performances of athletes of disparate bodyweights in Olympic weightlifting is developed that is able to accommodate the fact that, of the ten bodyweight classes contested, the lighter nine have upper limits assigned to them while the heaviest has only a lower limit. The results are presented so as to answer the question "What would a given athlete weighing x kilograms total if he were a +110 kg. athlete of the same level of ability?" PMID- 4017159 TI - 1001 disorders of the ear, nose and sinuses in scuba divers. AB - One thousand and one disorders of the ear, nose and sinuses in 650 SCUBA divers were analysed for anatomical distribution and causation. The outer, middle and inner ears made up 64.6% with a surprising 23.9% being related to the lower jaw, its teeth, attached muscles and the temporo-mandibular joint. Of the remaining, 3.1% were related to the nose, 6.6% to the sinuses and there was a miscellaneous group of 1.8%. Most outer ear infections seemed to be self-inflicted whilst the middle ear conditions were due to dysfunction of the Eustachian tube. The middle ear conditions were prevented by reducing nasal congestion as by cauterising the inferior turbinates of the nose, or by giving counselling in the technique of clearing the ears. Apart from Eustachian tube dysfunction in some, there is no clear lead as to causation of the inner ear complaints. Nasal treatment also relieves blockage of the ostia of the sinuses and thus sinus barotrauma. Overall the commonest preventable cause appears to be nasal congestion due to a variable mixture of infective or vasomotor rhinitis, allergic rhinitis, unilateral hypertrophy and a deviated nasal septum. PMID- 4017160 TI - Pharmacokinetics of methotrexate and 7-hydroxy-methotrexate in rabbits. AB - In rabbits the IV kinetics of MTX (1.33, 4 and 12 mg/kg) could be described by a linear three-compartment model with a terminal half-life between 2.4 and 3.6 h. During 8 h 50% of the dose was excreted into urine in unchanged form and 15% as the metabolite 7-OH-MTX. These fractions remained constant with increasing dose. In continuous infusion experiments (9-900 micrograms/kg X min MTX IV) a decrease of the renal MTX clearance with increasing plasma concentration was observed. This effect was nearly compensated by an increase of the extrarenal MTX clearance. After short-term infusion of 7-OH-MTX (4 mg/kg) a biexponential decline of 7-OH-MTX plasma concentrations was observed with a terminal half-life of 0.45 h. About 80% of the dose was regained from urine during 5 h. From the combined pharmacokinetic data a linear model was constructed for the calculation of 7-OH-MTX plasma concentrations after short-term MTX infusion. For the first 4 h after MTX application the predicted values were in good accordance with the 7 OH-MTX concentrations actually measured. PMID- 4017161 TI - Effects of amino acids on the transport and cytotoxicity of melphalan by human bone marrow cells and human tumor cells. AB - In human tumor cells freshly obtained from patients with breast cancer, ovarian cancer, or adenocarcinoma of unknown etiology and in normal human bone marrow cells, the cell-to-medium ratio (intracellular/extracellular concentration) in vitro of 5.42 microM melphalan rose rapidly to levels of 6-17 after 35 min at 37 degrees C in Dulbecco's phosphate-buffered saline containing bovine serum albumin and glucose. Only patient C (breast cancer) had received chemotherapy. In all cells studied, L amino acids (1 mM) such as leucine, glutamine, tyrosine, and methionine reduced the cell-to-medium ratio of melphalan at 3 and 35 min. There was a good correlation between the reduction of melphalan transport at 35 min in the heterogeneous nucleated bone marrow cell population by amino acids and their effect on melphalan cytotoxicity in the CFU-C system. Aminoisobutyric acid (A1B), a specific substrate of the A system of amino acid transport, at a concentration between 1 and 50 mM had no significant effect on melphalan uptake at 3 min in any of the human cells studied except those of patient C. At 35 min A1B (10 or 50 mM) significantly reduced the intracellular melphalan concentration in normal bone marrow cells and tumor cells from patients B and C. At 2 mM, 2-aminobicyclo-(2, 2,1)-heptane-2-carboxylic acid (BCH), a specific substrate of the L system of amino acid transport, reduced the cell-to-medium ratio to 70% of control at 3 and 35 min in human bone marrow cells. In tumor cells from patients A, B, D, and F, 2 mM BCH had no significant effect on melphalan uptake at 3 min; it slightly decreased uptake in tumor cells from patient C. At 35 min, 2 mM BCH significantly reduced melphalan transport in tumor cells from patients C and F only. The lack of a BCH-suppressible component to melphalan uptake into human tumor cells freshly obtained from previously untreated patients contrasts with the presence of this component in murine L1210 leukemia cells, murine P388 leukemia cells, and human tumor cell lines. This suggests that minor differences in melphalan transport may exist amongst species and also between human tumor cells which are freshly obtained and cell lines maintained in culture. PMID- 4017162 TI - Pharmacokinetics and disposition of 4'-O-tetrahydropyranyladriamycin in mice by HPLC analysis. AB - The plasma level of 4'-O-tetrahydropyranyladriamycin (THP) declined rapidly after IV injection to mice, with a t1/2(alpha) of 0.453 min. Only 1.2 micrograms/ml THP was detected 2 min after injection of 5 mg/kg. The drug was immediately transferred to various tissues, where the drug levels were much higher than the plasma concentration. In the lung and spleen, 8.26 and 13.6 micrograms/g THP was present, respectively, 2 h after administration. Major metabolites of THP were 13 dihydro-THP, ADM, 7-deoxyadriamycinone, and 7-deoxy-13-dihydro-adriamycinone. Only 1.12% of the dose had been recovered in the urine by 48 h after injection as THP and its metabolites, according to analysis by HPLC fluorospectroscopy. The observed disposition of THP was compared with that of adriamycin (ADM). The plasma disappearance and tissue transfer of THP were faster than those of ADM. THP levels in the spleen and lung were higher and those in the heart and liver were lower than the corresponding ADM levels. Drug levels declined more quickly in most tissues in the case of THP than of ADM. Tissue distributions after single bolus and multiple injections were also compared and discussed. PMID- 4017163 TI - A phase I and pharmacokinetic comparison of hepatic arterial and peripheral vein infusions of bisantrene for liver cancer. AB - Bisantrene (NSC-337766) was administered to five patients with cancer of the liver (one case of hepatocellular carcinoma, two of metastatic carcinoma of unknown primary, two of metastatic colorectal carcinoma). Under fluoroscopic guidance, percutaneous hepatic venous catheters were placed in five patients and percutaneous hepatic arterial catheters in four. A fifth patient's hepatic arterial catheter was implanted at laparotomy. Hepatic plasma flow was estimated by the Fick principle using peripheral vein indocyanine green infusion. On the first day of treatment, patients received a 2- or 4 h hepatic arterial infusion of bisantrene (130 mg/m2); peripheral venous, hepatic arterial, and hepatic venous timed blood samples were drawn during and for 18 h after drug infusion. On the second day of treatment, 2- or 4 h peripheral vein infusion of bisantrene (130 mg/m2) was followed by the same blood sampling schedule. Patients were followed weekly for toxicity. Four patients received only one course of treatment, while a fifth received two courses. All patients experienced leukopenia (median nadir 2400/mm3; range 1400-2700/mm3). Two patients developed fever after drug infusion. No antitumor responses were observed. Plasma bisantrene concentrations were measured by HPLC. Pharmacokinetic analyses are reported for four patients. The hepatic extraction ratio ranged from 15% to 49%, hepatic plasma clearances were 0.029-0.353 1/min/m2; peripheral vein areas under the concentration-time curve during hepatic arterial infusion ranged from 35% to 50% of peripheral vein areas under the curve during peripheral vein infusion. We conclude that hepatic arterial bisantrene infusion offers only modest pharmacokinetic advantage to the target organ or to the systemic circulation over peripheral vein infusion. PMID- 4017164 TI - Pharmacokinetics of teniposide (VM 26) after IV administration in serum and malignant ascites of patients with ovarian carcinoma. AB - Nine patients with ovarian carcinoma and malignant ascites treated with IV teniposide chemotherapy (30 mg/m2/30 min) entered this study. Plasma and peritoneal fluid levels were measured by an HPLC method with electrochemical detection. Plasma decay kinetics followed a triexponential function. A high variability of drug diffusion in ascites was noticed. Peak concentrations in ascites ranged from 1.6% to 20.5% of serum peak concentration. The concentration in peritoneal fluid reached a maximum level 6 h after the infusion ended. Teniposide was less slowly eliminated from ascites than from serum. The exposure of the inflammatory peritoneal fluid to the drug expressed by area under the concentration-time curve (AUC) was also subject to significant interindividual variation, ranging from 223 to 2332 micrograms/ml X min. However, the peritoneal AUC was correlated with serum AUC and with the systemic clearance of the drug. A significant relationship between gamma glutamyltranspeptidase and both systemic clearance and either the serum or the peritoneal AUC was found, suggesting that liver plays a role in drug disposition. PMID- 4017165 TI - A phase II study of sequential methotrexate and fluorouracil in advanced colorectal cancer. AB - Twenty-nine patients with advanced colorectal cancer were treated with methotrexate (MTX) 200 mg/m2 followed 1 h later by fluorouracil (FU) (1000 mg/m2) and 24 h later by oral leucovorin 20 mg every 6 h for six doses. The cycle was repeated every 2 weeks. Among the 25 evaluable patients there were 2 complete responses (confirmed by liver scan) and 5 partial responses. Although hematological toxicity was mild, there were four episodes of nonfatal sepsis. The majority of patients developed an erythematous scaly rash on the palms and soles plus eye irritation after six courses of chemotherapy. In addition, the sequential MTX-FU had to be discontinued in 6 of the 7 responders because of (a) severe chills, (b) severe hyperpigmentation, or (c) neurologic complications (ataxic gait or disorientation). These results indicate that this sequential MTX FU has modest activity in colorectal cancer but is associated with moderately severe toxicity. Only randomized trials of FU alone versus sequential MTX-FU can determine whether sequential MTX-FU has a therapeutic advantage over FU alone in the treatment of advanced colorectal cancer. PMID- 4017166 TI - Nephrotoxicity of lomustine. A case report and literature review. AB - A patient is presented who developed nephrotoxicity after therapy with lomustine (CCNU) for astrocytoma of the brain. Only three other cases of lomustine nephrotoxicity have been reported, and all cases have been associated with cumulative drug doses of greater than 1,500 mg/m2. The clinical and pathologic features of lomustine nephrotoxicity are reviewed. It is recommended that cumulative doses of more than 1,200-1,4000 mg/m2 lomustine be avoided because of the risk of nephrotoxicity. PMID- 4017167 TI - High-performance liquid chromatographic assay for simultaneous estimation of aminoglutethimide and acetylaminoglutethimide in biological fluids. AB - A simple rapid high-performance liquid chromatographic assay for simultaneous estimation of aminoglutethimide and its acetylated metabolite acetylamidoglutethimide in plasma, saliva, and urine is described. This assay is suitable for pharmacokinetic studies in normal subjects and patients receiving other medication in addition to aminoglutethimide. PMID- 4017168 TI - Dose-response curves after in vivo experimental chemotherapy: influence of route of administration on biological outcomes. PMID- 4017169 TI - Factors influencing benzo[a]pyrene metabolism in human mammary epithelial cells in culture. AB - We have examined the human mammary epithelial cell (HMEC) culture system developed in our laboratory for factors that might influence the metabolism of chemical carcinogens, specifically, the impact of interindividual variation and the effect of different culture conditions. Benzo[a]pyrene metabolism and DNA adduct formation in HMEC from 13 normal reduction mammoplasty specimens, from five nontumorous mastectomy tissues and from eight primary carcinomas were investigated. The interindividual variation in formation of water and organosoluble metabolites was similar in all of the three categories of HMEC. A similar range of variation was found for DNA adduct formation among HMEC from reduction mammoplasty specimens. However, when the individual results of DNA adduct formation in the three categories were examined, HMEC from some specimens from non-tumorous mastectomy tissue and primary carcinomas had significantly increased DNA modification. We also measured the effects of BaP concentration, different culture media, the length of time in culture, the culture density, and the frequency of feeding on the conversion of tritiated BaP to various water and organosoluble metabolites. The BaP metabolite pattern by HMEC was generally stable in the face of these variables. However, suboptimal feeding regimens and lengthy passaging in culture reduced the capacity of the cells to metabolize BaP. The yield of BaP conjugates was reduced 10-fold with lengthy passaging in culture whereas the organosoluble metabolite yield was halved and DNA adduct formation was not affected. Increasing the concentration of BaP decreased the yield of water soluble metabolites relative to that of organosoluble, indicating differences in the capacity of the enzyme systems involved. The HMEC culture system offers several advantages for studies into the biochemical and molecular basis of chemical carcinogenesis in human epithelial cells: the large numbers of cells required can be easily generated; cells at all stages can be frozen for future experiments with no loss in activity; and a high capacity for carcinogen activation is retained during long-term culture. PMID- 4017170 TI - Poly (ADP-ribose) is not involved in the rejoining of DNA breaks accumulated to high levels in u.v.-irradiated HeLa cells. AB - U.v. damage to the DNA of HeLa cells induces the polymerisation of ADP-ribose, but only if repair synthesis is inhibited so that incomplete repair sites (i.e., DNA breaks) accumulate to abnormally high levels. 3-Aminobenzamide greatly reduces the ADP-ribose polymerisation response. However, 3-aminobenzamide does not reduce the rate of rejoining of the accumulated breaks when the inhibition of repair synthesis is reversed. Therefore, rejoining of these DNA breaks (in contrast to the rejoining of other kinds of break) appears not to depend on activation of polynucleotide ligase by ADP-ribosylation. PMID- 4017171 TI - N-methyl-N-nitrosourea induces dysplasia and cell surface markers of neoplasia in long-term rat bladder organ cultures. AB - Untreated organ cultures of normal rat bladder can be maintained for long periods, up to 160 days, in a supplemented Waymouth's medium MB 752/1. During that time, the urothelium retains a similar appearance to that seen in vivo, namely a three-cell thick epithelium with specialised superficial cells whose characteristic surface features are identifiable by scanning electron microscopy. These superficial cells cover the major part of the explants, but the surface features of basal and intermediate cells can be observed on the cut edges and re epithelialising surfaces of the explant. These are described and illustrated. When normal cultures are treated with the direct-acting carcinogen, N-methyl-N nitrosourea (MNU), the in vitro response of the urothelium resembles to a certain extent the in vivo response to MNU instilled directly into the bladder. A histological progression is seen through mild to severe dysplasia which resembles carcinoma in situ. However, no marked changes in growth pattern, such as the development of papillary or nodular hyperplasia are seen. It is suggested that this is related to the failure of the vascular and stromal elements of the explants to respond to MNU treatment in vitro. The development of urothelial dysplasia is reflected by marked changes in cell surface differentiation, including development of pleomorphic microvilli, which closely resemble those seen following MNU treatment in vivo. These changes appeared earlier and were far more severe in vitro than in vivo. The significance of pleomorphic microvilli in bladder cultures is considered. A few were seen in control cultures but primarily on epithelial outgrowths onto the Millipore filter support, suggesting a relationship to the distance of the urothelium from viable stromal support. In the MNU-treated cultures, they were numerous and found on the surface of cells covering most of the explants. They were not solely related to the proliferative state of the urothelium in these cultures. This in vitro culture system provides a useful model with which to study the effects on the urothelium of various known and suspect carcinogens. PMID- 4017172 TI - Agglutination by concanavalin A of urothelial cells of heterotropically transplanted rat urinary bladders: effect of bladder carcinogens and urine. AB - N-butyl-N-(3-carboxypropyl)nitrosamine (BCPN) has been considered to be a carcinogenic urinary metabolite of N-butyl-N-(4-hydroxybutyl)nitrosamine. No tumor developed, however, in the heterotropically transplanted rat urinary bladders (HTBs) following repeated instillation of BCPN dissolved in physiological saline. In the present study, the possibility that BCPN dissolved in urine may induce tumors was explored using a short-term screening assay. When tested with the concanavalin A agglutination assay with which a close correlation between increase in cell agglutinability and carcinogenicity of test compounds has been well demonstrated, no significant increase in agglutinability attributable solely to BCPN was observed in HTB cells whether it was dissolved in saline or urine. Based on the current findings together with other available data, it is suggested that urothelial cells have a very limited capability to activate BCPN to the ultimate carcinogen, and require continuous contact with the carcinogen to respond with tumor formation. PMID- 4017173 TI - Toxicity of orally administered fat to the colonic epithelium of mice. AB - C57BL/6J mice were given a gavage of from 0.1 to 0.4 ml beef tallow (BT) or corn oil (CO). The damaging effect of the orally administered fat boluses could be visualized 2-4 h later by instilling the excised animal colons with Trypan blue, a vital dye that stains non-viable cells. Microscopic examination of sections prepared at these times revealed that the tall columnar cells on the surface of the normal epithelium were replaced with cells demonstrating flattened, pleomorphic, pyknotic and fragmented nuclei. This phenomenon was quantitated by scoring 100 intercrypt epithelial zones between well-defined crypts. The maximum damage, affecting 25-45% of the epithelial zones, was seen at 2-4 h after treatment with 0.4 ml of BT or CO and the epithelium appeared normal with less than 10% damage at 12 h. The mitotic activity in the colonic crypts was unchanged up to 8 h and then showed a marked increase of 2- to 3-fold at 12-16 h. The severity of the epithelial damage and ensuing mitogenic response was related to the size of the fat bolus. These observations would suggest that the effects of any carcinogens present in the diet or formed in the feces could be enhanced if a fatty meal results in colonic damage and subsequent cell proliferation as we have observed in mice. PMID- 4017174 TI - Target organ-specific covalent DNA damage preceding diethylstilbestrol-induced carcinogenesis. AB - The synthetic estrogen diethylstilbestrol (DES), a known human carcinogen, induces renal carcinoma in male Syrian hamsters within 6 months after s.c. implantation. Tumor formation could be evoked by its hormonal properties or by a reactive genotoxic metabolite binding to DNA, but previous attempts to detect adducts have failed. In the present study, kidney DNA of male Syrian hamsters, treated with s.c. DES implants to induce renal carcinoma, was analyzed for the presence of DES-induced adducts using 32P-postlabeling assay. Covalently-modified DNA nucleotides were detected in the kidneys after chronic DES treatment, but not in kidneys of untreated hamsters, or in liver or tumor tissue of DES-treated animals. This report demonstrates for the first time the ability of an estrogen to give rise to covalent DNA modification in vivo specifically in the target organ of carcinogenesis. DES-induced covalent DNA adducts are taken as evidence for tumor initiation by DES via damage to cellular macromolecules, in addition to tumor-promotional effects described previously. PMID- 4017175 TI - Retinoids have different effects on morphological transformation and anchorage independent growth of Syrian hamster embryo cells. AB - The effect of different retinoids on morphological transformation and anchorage independent growth of Syrian hamster embryo cells has been studied. Retinoic acid and its derivatives were found to induce morphological transformation of hamster embryo cells, and to synergistically increase the transformation frequency when exposed in combination with benzo[a]pyrene. The increase was maintained when the cells were sequentially exposed to benzo[a]pyrene and retinoids in a similar way as observed for tumor promoting phorbol esters. At the same time retinoids were found to strongly decrease anchorage independent growth of a hamster embryo cell line. The present results support previous findings indicating that retinoids may have an enhancing effect on the early stages in carcinogenesis, and an inhibitory effect on the later stages. PMID- 4017176 TI - Hepatic N-oxidation, acetyl-transfer and DNA-binding of the acetylated metabolites of the carcinogen, benzidine. AB - The metabolic N-oxidation, N-acetylation and N-deacetylation of the carcinogen benzidine (BZ) and its N-acetylated metabolites were examined in vitro with rat and mouse liver subcellular fractions. N-Oxidation of N-acetylbenzidine (ABZ) and N,N'-diacetylbenzidine (DABZ) was found to occur with NADPH-, NADH-fortified microsomes, although total oxidation at both nitrogens of ABZ was substantially faster than the N-oxidation of DABZ (four times for the mouse and 48 times for the rat). In both species, N-oxidation of ABZ to the arylhydroxylamine, N' hydroxy-N-acetylbenzidine (N'-OH-ABZ), was somewhat faster than the formation of the arylhydroxamic acid, N-hydroxy-N-acetylbenzidine (N-OH-ABZ). N-Acetylation of BZ and ABZ by liver cytosol was quite efficient for both species (0.7-2.9 nmol/min/mg cytosolic protein), and these rates were found to be 3-10 times faster than their corresponding rates of N-oxidation. N-Deacetylation of ABZ and DABZ by mouse liver microsomes occurred at a rate that was comparable with N acetylation; while N-deacetylation by rat liver microsomes was relatively slow, only 1-2% of the rate of N-acetylation. In the case of N-hydroxylated derivatives, N-OH-ABZ and N'-OH-ABZ, hepatic cytosolic N-acetylation by both rats and mice to form N-OH-DABZ was quite rapid (0.5-1.9 nmol/min/mg cytosol protein). Hepatic microsomal deacetylation of N-OH-DABZ also occurred with both species and was 2-4 times the rate of N-acetylation. These studies indicate that a significant concentration of potentially electrophilic monoacetylated N-oxidized metabolites may accumulate within the liver cell, and that they may serve as intermediates in the synthesis of the highly toxic metabolite, N-OH-DABZ. A major metabolic pathway for the formation of N-OH-DABZ is proposed as: BZ----ABZ----N' OH-ABZ----N-OH-DABZ. The activation of N-OH-DABZ by cytosolic N,O-acyltransferase and N'-OH-ABZ by cytosolic sulfotransferase and O-acetyltransferase (acetyl CoA dependent binding to DNA) were also examined. N-OH-DABZ N,O-acyltransferase and N'-OH-ABZ O-acetyltransferase were found to be significant pathways for rat and mouse liver, respectively. In addition, the DNA adduct formed from N-OH-DABZ in the presence of partially-purified rat hepatic N,O-acyltransferase was shown to be N'-(deoxyguanosin-8-yl)-N-acetylbenzidine, which is identical to that formed in rat liver in vivo and in the direct reaction of N'-OH-ABZ with DNA in vitro under acidic conditions.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 4017177 TI - Elevation of hepatic microsomal epoxide hydrolase activity by 2 acetylaminofluorene: role of metabolism. AB - Brief exposure of rats to hepatocarcinogenic agents causes a rapid elevation in hepatic microsomal epoxide hydrolase (EH) activity. Previous studies have demonstrated that animals which are resistant to the hepatocarcinogenic effects of 2-acetylaminofluorene (AAF) are also resistant to EH induction by this compound. The studies described here were designed to examine the role of several individual metabolic pathways on the induction of EH by AAF. EH was increased 4 fold in male Fischer 344 (F-344) or Sprague-Dawley (SD) rats treated with AAF; in female rats, deficient in N-hydroxylase and sulfotransferase activities, the activity was increased only 2-fold. Pretreatment of male F-344 rats with inducers of cytochrome P-448 activity caused a reduction in the EH response to AAF, probably due to a greater increase in ring-hydroxylation than N-hydroxylation of the AAF. Although AAF elicited only a small EH elevation in female F-344 rats, N hydroxy-2-acetylaminofluorene (N-OH-AAF) caused a large increase in these animals. The N-OH-AAF-induced increase was partially blocked by pretreatment with pentachlorophenol, an inhibitor of sulfotransferase activity, in both male and female F-344s. In female SD rats, possessing minimal sulfotransferase activity, N OH-AAF treatment caused only a slight elevation of EH activity. Pretreatment of male F-344 rats with inhibitors of deacetylase activity had no effect on N-OH-AAF dependent EH induction. These observations are consistent with the suggestion that formation of the sulfate conjugate of N-OH-AAF is necessary for elevation of EH by this compound. PMID- 4017178 TI - Benzo[a]pyrene-DNA adduct formation in target and activator cells in a Wistar rat embryo cell-mediated V79 cell mutation assay. AB - To determine the relationship of the benzo[a]pyrene (BaP)-DNA adducts formed in the activator cells of a cell-mediated mutation assay to the adducts formed in the target cells and to mutation induction, irradiated second passage Wistar rat embryo (WRE) cells and V79 Chinese hamster lung cells were exposed to [3H]BaP for 5, 24 and 48 h under the conditions of a cell-mediated mutation assay. The V79 target cells were separated from the WRE activator cells by an immunoseparation procedure; the resulting V79 cell pellet contained less than 7% WRE cells. The percentage of the BaP-DNA adducts containing cis vicinal hydroxyl groups and the h.p.l.c profile of individual adducts in the V79 target cells were similar to those of the WRE activator cells for each time point. The transfer of reactive BaP metabolites from the activator cells to the target cell DNA was detectable after only 5 h of exposure to BaP, however, exposure for this length of time did not result in significant mutation induction. The (+)-7,8-dihydroxy-9,10-epoxy 7,8,9,10-tetrahydrobenzo[a]pyrene (anti-BaPDE)-deoxyguanosine (dGuo) adduct was essentially absent after 5 h of exposure, but the amount of this adduct increased at longer times of exposure as did the mutation frequency. The complex mixture of BaP-DNA adducts formed in the WRE cells was also present in the V79 cells after all three times of exposure to BaP, a result which demonstrates the value of this cell-mediated mutation assay for investigating the role of species-specific differences in the activation of BaP. The correlation between the increase in mutation induction and the relative amount of the (+)-anti-BaPDE-dGuo adduct present in V79 cell DNA suggests the importance of this adduct in mutation induction by BaP. PMID- 4017179 TI - Measurement of O6-methyldeoxyguanosine in DNA methylated by the tobacco-specific carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone using a biotin-avidin enzyme-linked immunosorbent assay. AB - Rabbit antibodies raised against O6-methyl-2'-deoxyguanosine (O6-MedGuo) were used to develop a competitive Biotin-Avidin enzyme-linked immunosorbent assay (BA ELISA) for the quantitation of this adduct in DNA from animals exposed to tobacco specific N-nitrosamines. The assay was able to detect as little as 30 mumol O6 MedGuo per mol deoxyguanosine. The specificity of the assay was at least 10 000 fold greater for O6-MedGuo than for unmodified nucleosides or 7-methyl-2' deoxyguanosine. The sensitivity of the assay was increased to 1 mumol O6-MedGuo per mol deoxyguanosine by the prior separation of O6-MedGuo from unmodified nucleosides by h.p.l.c. This assay was used to study the methylating ability of the tobacco-specific nitrosamine 4-(methyl-nitrosamino)-1-(3-pyridyl)-1-butanone (NNK) in F344 rats. Four hours after exposure to a single i.v. dose of NNK O6 MedGuo was detected in the target tissues nasal mucosa, lung and liver (219, 13.2 and 34.5 mumol/mol deoxyguanosine) but not in the non-target tissues esophagus, spleen, heart or kidney. Chronic exposure by 14 daily i.p. injections of NNK also resulted in detectable amounts of O6-MedGuo in the lung and nasal mucosa (11.4 and 7.9 mumol/mol deoxyguanosine). These results demonstrate that NNK is capable of methylating DNA in vivo. The methodology developed in these studies will allow us to examine in detail the role of DNA methylation in NNK-mediated carcinogenesis. PMID- 4017180 TI - Microsome-mediated alkylation of rat liver initiator tRNA by 3,3-dimethyl-1 phenyltriazene and its ring-chlorinated derivatives. AB - 3,3-[3H]Dimethyl-1-phenyltriazene, 1-(4-chlorophenyl)-3,3-[3H]dimethyltriazene and 3,3-[3H]dimethyl-1-(2,4,6-trichlorophenyl)-triazene methylate initiator tRNA in vitro only after pre-incubation with microsomal enzymes and NADPH. The finding confirms that procarcinogenic dialkyl aryltriazenes must be enzymatically converted into reactive metabolites, presumably into the corresponding monoalkyltriazenes, which ultimately react with tRNA. The methylation at 37 degrees C requires 40-60 min and individual triazenes showed differential alkylating capacity if tRNA was the limiting factor. Enzymatic hydrolysis of the modified initiator tRNA, followed by separation of nucleosides on Sephadex G10 or Dowex 50 columns, revealed that 7-methylguanosine was the principal labelled product. The methylated tRNA showed a significantly increased acceptance for L methionine. It appears that methylation of initiator tRNA at N7 of guanine affected the conformation of initiator tRNA and rendered the nucleic acid more accessible for cognate aminoacyl-tRNA synthetase. PMID- 4017181 TI - Growth inhibition and transformation of a human fetal tracheal epithelial cell line by long-term exposure to diethylnitrosamine. AB - In order to obtain more information on the in vitro transformation of human cells, a human fetal tracheal epithelial cell line (FHET16/5) was exposed for a long time to diethylnitrosamine (DEN). In 20 passages, this cell line (diploid, male) maintained strong immunohistochemical reactivity for carcino-embryonic antigen and wool merokeratin; it was negative for vimentin. The cells contained PAS-positive mucous substances and ultrastructurally were found to have desmosome like attachments. Treatment of the cells was with 0.3% dimethyl sulphoxide (DMSO), or DMSO with 150, 450, 1000 or 2000 micrograms/ml of DEN. It was started at the ninth passage and continued for six passages over 9 weeks for the control (DMSO) and the three lowest control doses of DEN, and for three passages over 9 weeks for the 2000 micrograms/ml DEN group. Cells grown for 13 days after the end of treatment were plated in soft agar and injected subcutaneously in nude mice. The frequency of anchorage-independent colonies grown in soft agar was directly related to DEN dose. Colony-forming efficiency, as an expression of toxic effect, was also dose dependent. Autoradiographically detected unscheduled DNA synthesis indicated an association between anchorage-independent transformation and DNA alterations induced by DEN. Cells injected into nude mice did not produce tumours during a 6-month period, but invasiveness was observed when cells from the 2000 micrograms/ml DEN group were transplanted on the dermis of cultured chick embryo skin. The results indicate that DEN causes anchorage-independent transformation accompanied by unscheduled DNA synthesis in a fetal human tracheal epithelial cell line. PMID- 4017182 TI - Benzo[a]pyrene-induced DNA damage in mouse fetal tissues. AB - We have studied the occurrence and persistence of DNA damage in the hepatic and pulmonary tissues of fetal, newborn and adult CD1 mice exposed to selected doses of benzo[a]pyrene (BP) by utilizing the alkaline elution technique. Firstly 12-, 15- and 18-day pregnant and 1-, 7- and 82 to 85-day-old mice were treated i.p. with 10 mg/kg BP and the DNA fragmentation evaluated 4 h later. This approach indicated that, among the ages considered, 15-day-old fetuses were the most sensitive to BP genotoxicity. Therefore we concentrated on this intrauterine stage and evaluated the role of the maternal and fetal environment on the induction and the kinetics of disappearance of DNA damage by BP. BP at the dose levels of 0, 2 and 10 mg/kg was injected i.p. into pregnant females or directly into single fetuses and the fetal livers and lungs recovered 2, 4, 24 and 48 h later. According to the above protocol other 12-day-pregnant mice were treated i.p. with 500 mg/kg arochlor and their 15-day-old fetuses directly injected with the same doses of BP. The results showed that the maximum DNA damage is present at 4 h following BP treatment and it almost disappeared at 48 h irrespective of the route of BP administration. However, the decrease was not uniform and while at 48 h the lesion reached the control level in the liver, it remained slightly higher in the lung. The effects where markedly magnified in the arochlor-induced groups where the intrafetal injection of BP caused an average 2-fold increase and an earlier appearance of DNA damage in both liver and lung compared with uninduced animals. The amplified BP activity induced by arochlor was particularly evident in the lung where at 48 h there was still a significant amount of DNA damage. Since the lung is a preferential site of transplacental carcinogenic effects in CD1 mice, our results favor the conclusion that a correlation exists between DNA damage and tumor induction in the fetuses of this mouse strain. PMID- 4017183 TI - Studies in gastric carcinogenesis. II. Absence of elevated concentrations of N nitroso compounds in the gastric juice of Greek hypochlorhydric individuals. AB - The concentrations of nitrate, nitrite, N-nitroso compounds and bacteria were measured in 96 samples of fasting gastric juice, pH 0.90-8.50, obtained from 56 individuals just before or at various times (8 days - 1 year) after gastric operation. The mean pH of the post-operative samples [4.66 +/- 0.39 (SEM)] was significantly higher than that of the pre-operative ones [3.29 +/- 0.33 (SEM)]. A positive correlation with pH was observed for the concentrations of total and nitrate-reducing bacteria (median values 5.0 X 10(5) organisms/ml and 9.2 X 10(4) organisms/ml, respectively, for samples with pH greater than or equal to 1.2 X 10(3) organisms/ml and 0 organisms/ml, respectively, for samples with pH less than or equal to 2.5) and nitrite [mean values 22.5 +/- 3.1 (SEM) microM and 3.20 +/- 0.5 (SEM) microM for samples with pH greater than or equal to 6.5 and pH less than or equal to 2.5, respectively]. No correlation with pH was seen for the concentrations of nitrate [mean value 0.48 +/- 0.06 (SEM) mM] or N-nitroso compounds [mean value 0.30 +/- 0.06 (SEM) microM]. The concentrations of bacteria and nitrite, although increased in hypochlorhydric individuals, were lower than those reported for corresponding individuals in other, primarily British, studies. It is suggested that the relatively low concentrations of nitrite observed in our hypochlorhydric population may account for the absence of elevated concentrations of N-nitroso compounds and that the latter phenomenon may be related to the relatively low frequency of gastric cancer in Greece. PMID- 4017184 TI - Studies in gastric carcinogenesis. III. The kinetics of nitrosation of gastric juice components in vitro and their implications for the in vivo formation of N nitroso compounds in normal and in hypochlorhydric populations. AB - Fasting human gastric juice was treated in vitro, at pH 2-7 and 37 degrees C for 2 h, with 5-100 microM sodium nitrite. Under these conditions (which simulated those occurring in vivo in normal or hypochlorhydric individuals), the formation of total N-nitroso compounds had the following characteristics: (i) it increased greatly at pH less than 3; (ii) it showed first-order dependence on nitrite concentration; (iii) it was faster at pH 7 than at pH 5. These observations are compatible with the N-nitroso compounds formed by the interaction of nitrite with gastric juice being N-nitrosamides or related compounds. Furthermore, based on the results of this study, it is suggested that in order for hypochlorhydria to give rise to increased formation of N-nitroso compounds in the stomach, it would be necessary for it to be accompanied by a greater than 5- to 10-fold increase in gastric nitrite concentration relative to that found in the normal population, a condition which is not necessarily fulfilled in all hypochlorhydric individuals or populations. The implications of this conclusion for the assessment of the role on gastric N-nitroso compounds in the etiology of gastric cancer are discussed. PMID- 4017185 TI - Effects of calcium and magnesium salts on nickel subsulfide carcinogenicity in Fischer rats. AB - The effects of calcium or magnesium salts administered by one of three different routes on the formation of muscle tumors by nickel subsulfide (Ni3S2) in Fischer F344 rats were determined. Eleven groups of 20 weanling male rats each received a single injection of 2.5 mg (31 mumol Ni) Ni3S2 into the thigh muscles of both hind limbs (i.m.). Then the rats were fed 3% calcium acetate (CaAcet)- or 3% magnesium acetate (MgAcet)-supplemented diets for 3 and 6 months, or were injected s.c. three times weekly, with 0.16 mmol doses of CaAcet/kg/injection, or with 2 mmol doses of MgAcet/kg/injection, for 1 or 4 months. Two other groups of 20 rats were injected i.m. with 2.5 mg (31 mumol Ni) of Ni3S2 mixed with 6.2 mg (62 mumol Ca) of calcium carbonate (CaCarb), or with 6.3 mg (62 mumol Mg) of magnesium basic carbonate (MgCarb). The control groups of rats received single i.m. injections of the 0.15 M saline vehicle, 6.2 mg CaCarb, and 6.3 mg MgCarb, or s.c. injections of 0.15 M saline, or 4 mmol sodium acetate, NaAcet/kg/injection, three times weekly for 4 months. After 18 months, injection site tumors were found: (i) in 70-90% of the rats injected i.m. with Ni3S2 and fed standard diet or the diets containing CaAcet or MgAcet, with no significant differences among the groups; (ii) in 95-100% of the rats given i.m. Ni3S2 and then treated with multiple s.c. injections of saline, NaAcet, CaAcet or MgAcet, with no significant differences among the groups; (iii) in 85% of rats injected i.m. with Ni3S2 + CaCarb, and (iv) in 25% of the rats injected i.m. with Ni3S2 + MgCarb. No tumors developed in the control rats. The admixtures of CaCarb or MgCarb to Ni3S2 did not affect the mobilization of nickel from the injection site. They did, however, influence the cellular responses to Ni3S2 in early stages, from 3 days to 22 weeks, after the injection. MgCarb, unlike CaCarb, strongly decreased the necrosis and increased macrophage proliferation at the Ni3S2 injection site. It also delayed the occurrence and proliferation of histiocytic-stromal cells, and prevented the occurrence of altered myoblasts. PMID- 4017186 TI - Normal and transformed human prokeratinocytes express divergent effects of a tumor promoter on cell cycle-mediated control of proliferation and differentiation. AB - The tumor promoter, 12-O-tetradecanoylphorbol-13-acetate (TPA), is shown to be a potent inhibitor of growth of normal human prokeratinocytes (HPK) cultured in serum-free medium. More specifically TPA inhibits the clonal growth of low density HPK cultures in a dose-dependent manner and the anti-proliferative effect of TPA is selective in that the inactive phorbol diester, 4-alpha-12,13-phorbol didecanoate, does not exert a similar effect. One-hour pulse exposure of HPK to TPA also has an effect comparable with continuous exposure to TPA; both treatments induce rapid growth arrest. Flow cytofluorometric analysis of DNA content shows that in TPA-treated HPK growth arrest is associated with accumulation of cells in both the G1 and G2/M phases of the cell cycle. Most interestingly, the data establish that the growth arrest of HPK induced by TPA is irreversible in that treated cells lose their colony-forming potential and that such cells are committed to differentiate without further cell cycle progression when placed in differentiation-promoting medium. In contrast, a human squamous carcinoma cell line, designated SCC-25, is insensitive to the anti-proliferative effect of TPA regardless of whether these cells are cultured in either serum containing or serum-free medium. These data are interpreted to suggest that transformed human epithelial cells SCC-25 are defective in their ability to regulate their proliferation and differentiation by TPA-sensitive cell cycle dependent mechanisms. PMID- 4017187 TI - Quantification of 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) and 2-amino-3,8 dimethylimidazo[4,5-f]quinoxaline (MeIQx) in beef extracts by liquid chromatography with electrochemical detection (LCEC). AB - A simple and sensitive method was developed for quantification of mutagenic/carcinogenic aminoimidazoquinoline and aminoimidazoquinoxaline compounds in heated materials. Samples were partially purified by blue-cotton treatment, 0.1 N HCl-methylene dichloride partition and separation in a SEP-PAK silica cartridge. The recoveries of aminoimidazoquinoline and aminoimidazoquinoxaline compounds at the step of partial purification were estimated by spiking with 14C-labeled compounds. The compounds in partially purified materials were analyzed by liquid chromatography with electrochemical detection using a combination of two columns of octadecyl silane and cation exchange. Bacteriological-grade beef extract was found to contain 41.6 and 58.7 ng/g of 2-amino-3-methylimidazo[4,5-f]quinoline and 2-amino-3,8 dimethylimidazo[4,5-f]quinoxaline (MeIQx), respectively. MeIQx was also detected at a level of 3.1 ng per g in food-grade beef extract. PMID- 4017188 TI - Unscheduled DNA synthesis caused by norethindrone and related contraceptive steroids in short-term male rat hepatocyte cultures. AB - The genotoxic potential of oral contraceptive steroids such as norethindrone was investigated in short-term rat hepatocyte cultures by measurement of unscheduled DNA synthesis. Norethindrone caused a small dose-dependent increase in unscheduled DNA synthesis in male rat hepatocytes as judged by the incorporation of [methyl-3H]thymidine into DNA. This was assessed either by liquid scintillation counting following isolation of DNA or by autoradiography. No increase in unscheduled DNA synthesis could be detected in female rat hepatocytes treated with norethindrone. Pre-treatment of male rats with phenobarbitone prior to hepatocyte preparation decreased the norethindrone mediated unscheduled DNA synthesis relative to control hepatocyte cultures while 3-methylcholanthrene pre treatment had little effect. Unscheduled DNA synthesis in norethindrone treated control male rat hepatocytes was reduced by the mixed function oxidase inhibitors SKF 525A or metyrapone. In 24- or 52-hour-old hepatocyte cultures in which the cytochrome P-450 content was lower than in freshly prepared cells, or in a hepatocyte-derived cell line lacking cytochrome P-450, unscheduled DNA synthesis due to norethindrone was either decreased or abolished. Structure activity studies showed that only steroids containing a 17 alpha-ethynyl substituent caused an increase in unscheduled DNA synthesis. PMID- 4017189 TI - Hereditary interindividual differences in the glutathione transferase activity towards trans-stilbene oxide in resting human mononuclear leukocytes are due to a particular isozyme(s). AB - We have shown earlier that there are large, hereditary interindividual differences in the cytosolic glutathione transferase activity towards trans stilbene oxide in human mononuclear leukocytes. In the present study we ask whether these differences reflect the presence or absence of a particular isozyme(s) of glutathione transferase. First, in order to measure the high glutathione transferase activity optimally it was necessary to modify our previous assay by increasing the concentration of reduced glutathione from 3 to 5 mM and of the substrate from 50 to 250 microM. It was then found that the low activity demonstrates an apparent Km for trans-stilbene oxide of 28.3 microM, whereas the corresponding value for the high activity was 127 microM. Secondly, it was found that while glutathione transferase activity towards trans-stilbene oxide in different individuals segregated into three groups, low, high and very high, glutathione transferase activity towards 1-chloro-2,4-dinitrobenzene in these same mononuclear leukocyte fractions formed only a single group with no tendency towards such segregation. Thirdly, the SDS-poly-acrylamide gel electrophoretic pattern obtained with the supernatant fraction from mononuclear cells demonstrating high glutathione transferase activity towards trans-stilbene oxide contained a band of 25 000 molecular weight which was either absent or present at a much lower level in cells demonstrating low activity. We conclude that high activity towards trans-stilbene oxide in circulating, resting human mononuclear cells is catalyzed by a particular isozyme(s) of glutathione transferase. cis-Stilbene oxide, styrene oxide and, possibly, benzo[a]pyrene 4,5 oxide are also substrates for this isozyme(s). PMID- 4017190 TI - A comparative examination of the in vitro metabolism of five cyclopenta[a]phenanthrenes of varying carcinogenic potential. AB - Metabolites of 15,16-dihydrocyclopenta[a]phenanthren-17-one and its 1- and 12 methyl homologues (all non-carcinogens) along with those from the 11-methyl and 11,12-dimethyl-17-ketones (carcinogens), produced in vitro by hepatic microsomes from methylcholanthrene induced rats, were separated by reverse phase h.p.l.c. Identifications of individual metabolites were based upon elution times, u.v. spectra, and in some cases by mass spectrometry, circular dichroism, and identity with synthetic derivatives. All five compounds were biologically oxidised at their terminal A and D rings to yield 1,2-dihydrodiols and 15- and 16- ols; with the exception of the 1-methyl compound, all also gave similar amounts of 3,4 dihydrodiols. The 1-methyl compound by contrast failed to produce this metabolite, furnishing instead the 4-phenol and five other, probably related phenolic derivatives. Previous work has established that for the 11-methyl-17 ketone, the 3,4-dihydrodiol is the proximate carcinogen. Thus, whereas lack of biological activity with the 1-methyl compound can be ascribed to its failure to produce a 3,4-dihydrodiol, in the case of the unsubstituted parent ketone and its 12-methyl derivative other determining factors must come into play. PMID- 4017191 TI - Comparison of the binding of some carcinogenic and non-carcinogenic cyclopenta[a]phenanthrenes to DNA in vitro and in vivo. AB - After microsomal activation in vitro, both the strong carcinogen 15,16-dihydro-11 methylcyclopenta[a]phenanthren-17-one and its inactive 12-methyl isomer bind covalently to added DNA, in the ratio approximately 6:1 (1595 and 254 mu mol/mol of DNA phosphorus, respectively). Over a thousand times less binding was observed when DNA was isolated from the skin of groups of mice that had received a topical dose of 1000 nmol of these two compounds, and of the unsubstituted ketone (non carcinogen) and its 11,12-dimethyl derivative (carcinogen), 48 h previously; the binding ratios were 458, 155, 19 and 974 nmol/mol DNA phosphorus, respectively. Covalent binding of the 11-methyl compound to mouse skin DNA, measured 48 h after topical application, was linear with dose over the range 50 - 1000 nmol. It has previously been demonstrated for groups of mice initiated with 200 or 400 nmol of this carcinogen and promoted by repeated application of croton oil that skin tumour incidences were 50 and 70%, respectively. For a topical dose of 1000 nmol of the inactive 12-methyl isomer DNA binding in skin falls in this range, equivalent to DNA binding given by approximately 340 nmol of the carcinogen. Thus although the inactive unsubstituted parent compound essentially fails to bind to skin DNA after topical application, there does not seem to be a consistent relationship between extent of DNA binding in vivo and carcinogenicity among these cyclopenta[a]phenanthrenes. However, loss of the 12-methyl adducts from skin followed a logarithmic course over the first 10 days following application, with a half life of 3.5 days. In contrast, it was previously shown that removal of the 11-methyl adducts could not be measured above the normal rate of DNA turnover for this mouse tissue (half life, 6-7 days). It is suggested that active DNA repair of the 12-methyl lesions may contribute to the lack of activity of this isomer. PMID- 4017192 TI - Health education needs of primigravidae. AB - Forty-eight primigravidae were interviewed when 3-4 months pregnant about their knowledge of fetal development, awareness of hazards to development and sources of information. Although there was reasonable knowledge about normal fetal development, the women were not generally aware of the repercussions of maternal rubella or rationale for many routine tests at antenatal clinics. Fourteen of the women were smoking and only four of these intended to change during pregnancy. The general practitioner was perceived as a vital source of information, in marked contrast to the midwife. Few women reported learning about child development or care at school, but most used pamphlets or books as a source of information. PMID- 4017193 TI - The themes and consequences of consultations between a psychiatrist and a tutorial class teacher working with children from a deprived inner-city area. AB - This article describes the way in which consultation sessions between a tutorial class teacher and a psychiatrist were set up, and the themes that arose during the first term. We discuss the effect of the consultation on the relationship of the teacher with other professionals in her network. A hypothesis is put forward about the way in which the consultation caused changes which reduced the stress the teacher experienced. PMID- 4017194 TI - Using primary-school children to improve child-rearing practices in rural Jamaica. AB - Many children in Jamaica suffer from poor development, inadequate dental care and low immunization status. There is a need for low-cost innovative programmes to reach these children. We piloted an approach to teaching primary-school children basic child health and development concepts with the aim of improving their knowledge and practices and those of their guardians. The programme was conducted with 89 children from three grade levels in a remote rural school. The topic was taught throughout the school year with an action-oriented curriculum. Evaluation showed improvement in school children's knowledge and practices and guardians' knowledge. This approach is seen to be a feasible, low cost way of improving the quality of future child care. PMID- 4017195 TI - Achievement of infants on items of the Griffiths scales: 1980 compared with 1950. AB - As a preliminary to the revision of the Griffiths scales, 79 examiners throughout Britain tested 447 infants under the age of 2 years during 1978-1982. Compared with the original standardization sample of 1947-1951, the 1980 sample mean general quotient (GQ) was significantly higher, even after adjustments had been made for a slightly skewed social class distribution. Nor did regional differences between samples account for the GQ differences. Unreliable items were not significantly more common among those where the median age at passing had changed most. Various technical difficulties in representing differences between samples were encountered and dealt with. A population's overall results may be given in terms of mean score increase per month, median age advance in weeks or months, e.g. per year, and increase in general developmental quotient. Findings of differences between populations in age at passing individual items can be given as advances in median age, but are better expressed as ratios of the median ages of the two samples in order to deal with the differences in the chronological age for which items are designed. Only then can items be compared for amount of change. In terms of score and mental age advances the second year appears more changed than the first, but in terms of GQ the reverse is true. The locomotor scale mean differs more than other scales from the original norms for both years of infancy, while the personal-social scale differs more in the first year. Taking the most cautious estimate of differences from the data available on both samples, at least 160 items are now passed earlier than in the 1950 sample and the ratio of 1950 to 1980 ages is greater than 110 for 83 of those. Further study of the Griffiths scales items, in relation to one another and to cultural factors, seems feasible on the basis of steps illustrated in this paper. PMID- 4017196 TI - Efflux of metabolized and nonmetabolized fatty acid from canine myocardium. Implications for quantifying myocardial metabolism tomographically. AB - It has generally been assumed, from assessment of myocardial metabolism with [1( 11)C]palmitate and positron emission tomography, that clearance of the radiolabel from the myocardium is attributable solely to efflux of the products of oxidative metabolism. However, interpretations would differ if this assumption were unfulfilled. Furthermore, efflux of metabolized and nonmetabolized tracer has not been quantified. Accordingly, in this study, myocardium was perfused extracorporeally in 21 open-chest anesthetized dogs, and the extraction and clearance of [1(-11)C]palmitate were characterized under baseline conditions (normoxia, n = 21), and, again, with ischemia (n = 6), with hypoxia (n = 9), or under control conditions (n = 6). After intracoronary bolus injection of [1( 11)C]palmitate, myocardial time activity curves were measured with a beta-probe, and the products of oxidative metabolism (11CO2) and efflux of extracted but nonmetabolized fatty acid ("back-diffusion" of [1(-11)C]palmitate) were measured directly from analysis of arterial and regional coronary venous blood. Under control conditions, 45.2 +/- 3.8% (mean +/- SD) of initially extracted [1( 11)C]palmitate was metabolized to 11CO2, whereas 6.2 +/- 2.6% back-diffused in unaltered form in 1-10 minutes. In contrast, with ischemia (perfusion of 26% of baseline), only 16.9 +/- 9.8% of administered tracer evolved as 11CO2 (P less than 0.001 compared with control) but 15.6 +/- 8.9% (i.e., almost half of the total amount cleared) evolved unaltered as [1(-11)C]palmitate (P less than 0.05). Similarly, with hypoxia, 15.1 +/- 8.4% evolved as 11CO2 (P less than 0.0001) and 18.8 +/- 11.7% back-diffused (P less than 0.001). Overall, from 1-40 minutes after intracoronary injection of tracer, back-diffusion of [1(-11)C]palmitate contributed 40.6% of total radioactivity in the effluent with ischemia, 48.7% with hypoxia, but only 8.9% under control conditions. Despite the increased back diffusion of [1(-11)C]palmitate seen with ischemia and hypoxia, the overall residue of 11C activity in myocardium increased, consistent with the diminished clearance observed in the myocardial time-activity curves and the increase in the tissue content of triglyceride and nonesterified fatty acid. Our results indicate that estimates of oxidative metabolism based upon clearance of radiolabeled fatty acid must take into account the efflux of initially extracted but nonmetabolized fatty acid. The findings apply to external determination of oxidative metabolism of the heart with any imaging modality that delineates retention and clearance of labeled fatty acids or their analogs. PMID- 4017197 TI - Variations in the functional electrical coupling between the subendocardial Purkinje and ventricular layers of the canine left ventricle. AB - Action potential propagation from the subendocardial Purkinje network into the ventricular muscle is an essential link in cardiac activation. Studies of papillary muscles have indicated that ventricular muscle activation by the Purkinje network occurs only at discrete, localized regions near the papillary muscle base. Over the rest of the endocardial surface, however, the spatial distribution of these subendocardial Purkinje to ventricular muscle connections has been less well defined. We therefore studied in vitro 12 canine left ventricular preparations (eight from the septum, four from the lateral wall), using a high-density (1-mm spacings), high-resolution extracellular mapping technique to determine the subendocardial Purkinje and ventricular muscle activation sequences. These studies show that the distribution of subendocardial Purkinje to ventricular muscle electrical coupling is spatially inhomogeneous, and that the junctional regions themselves have variable degrees of electrical coupling. We also attempted to determine whether ventricular muscle coupling to the Purkinje network might influence Purkinje network conduction velocity. We found that on the papillary muscle apex, a region without direct Purkinje to ventricular muscle propagation, Purkinje network conduction velocity was slowed, suggesting that the Purkinje network might be electrically loaded by the underlying ventricular muscle. Finally, we performed numerical simulations using a model consisting of two layers of excitable cells to evaluate the effects that different electrical coupling patterns and/or different coupling resistivities between the two layers might have on activation of each layer. These simulation studies suggest that a coupling pattern having discrete junctional sites between the two layers (similar to our findings for subendocardial Purkinje to ventricular muscle coupling) is beneficial, as this arrangement allows more rapid activation of both layers by minimizing electrical loading of the thin Purkinje layer by the thicker ventricular muscle layer. PMID- 4017198 TI - Stability of heterogeneity of myocardial blood flow in normal awake baboons. AB - Regional myocardial blood flow has been thought to be relatively uniform, in accord with the singular function of myocardial cells. However, considerable spatial heterogeneity has been observed in the hearts of anesthetized animals and in isolated hearts. Studies were undertaken in a total of 13 baboons. Eleven were awake, healthy animals sitting in chairs at rest or feeding, some performed mild leg exercise (wheel turning), and others were subjected to whole body heating; two were anesthetized, methodological controls. Microspheres (15 +/- 3 micron diameter, 0.5 X 10(6)/kg body weight) were injected via a catheter into the apex of the left ventricle while arterial blood was sampled at a constant rate for calculating cardiac output. Microspheres with different labels were injected at six intervals of 20 minutes to several hours. On sacrifice, the hearts were sectioned into 204 locatable pieces (left ventricle, 168; right ventricle, 27; and atria, 9). Average resting myocardial flow was 2.1 +/- 0.2 ml/g per min (mean +/- SD, n = 11). Left and right ventricles and atria comprised 70 +/- 2% (n = 13), 20 +/- 2%, and 10 +/- 2% respectively of the total heart mass while receiving 80 +/- 3%, 16 +/- 2%, and 4 +/- 2% of the total myocardial flow. Thus, mean left ventricular flow was 114 +/- 5% of the average for the whole heart, right ventricular flow was 81 +/- 13%, and atrial flow was 41 +/- 13%. Myocardial flow heterogeneity was marked; in left ventricle, regional flows ranged from one third to two times the mean, the relative dispersion (= standard deviation/mean) of regional flows, corrected for methodological scatter and temporal variation, was 0.33 +/- 0.06 (n = 67) in the whole heart, 0.26 +/- 0.07 in left ventricle, 0.32 +/- 0.11 in right ventricle, and 0.22 +/- 0.19 in the atria. The pattern of regional flows in each heart tended to remain stable with time. In each piece averaged over time, the relative dispersion due to temporal heterogeneity was 0.11 +/- 0.03 (n = 2040) in the whole heart, 0.09 +/- 0.03 in the left ventricle, 0.15 +/- 0.05 in the right ventricle, and 0.23 +/- 0.06 in the atria. The conclusion is that the degree of spatial heterogeneity of local myocardial flows in conscious primates is similar to that of anesthetized animals and isolated hearts, and is much greater than that due to temporal fluctuations. PMID- 4017199 TI - Diabetes-induced alterations in the translational activity of specific messenger ribonucleic acids isolated from rat hearts. AB - During diabetes mellitus, total proteins and ribonucleic acids are significantly decreased in the rat heart, and these parameters can be increased by insulin administration. To determine whether all ribonucleic acids are equally sensitive to insulin, we examined the influence of this hormone on individual translatable ribonucleic acids. Cardiac ribonucleic acid prepared from control, untreated, and insulin-treated diabetic animals was translated in vitro in the presence of [35S]methionine. The radiolabeled peptides were separated by two-dimensional gel electrophoresis and were analyzed by fluorometry. We found that diabetes induces both qualitative and quantitative changes in the predominance of a few specific translatable messenger ribonucleic acid species. The translation of 11 messenger ribonucleic acid species was significantly decreased and that of eight messenger ribonucleic acid species was significantly increased in diabetic preparation. Twelve of the 19 translation products were quantified by digital matrix photometry: three labeled peptides were observed only when cardiac ribonucleic acid from diabetic animals was added to the cell-free translation system, four new peptides appeared when cardiac ribonucleic acid from control animals was added, and although the remaining five peptides were translated in vitro after either control or diabetic ribonucleic acid was added, their relative predominance was altered 2- to 200-fold. When translation products coded for by messenger ribonucleic acids prepared from either diabetic or hypothyroid hearts were compared, we found that most of the alterations induced by diabetes were also induced by hypothyroidism.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4017200 TI - Enhanced myogenic depolarization in hypertensive cerebral arterial muscle. AB - We have previously demonstrated pressure-dependent membrane depolarization and action potential generation in cat cerebral arteries. It was the purpose of this study to examine and compare the membrane electrical responses to increasing transmural pressure in spontaneously hypertensive rats with those of their normotensive Wistar-Kyoto controls. It was found that at transmural pressures from 40-160 mm Hg, spontaneously hypertensive rat cerebral arterial muscle depolarized more than normotensive counterparts. Pressure-induced action potentials could be recorded from arterial segments from both animal strains; however, the amplitude and upstroke velocity was significantly greater in spontaneously hypertensive rat cerebral arterial muscle. These data suggest that there are altered ionic permeabilities in spontaneously hypertensive rat cerebral arterial muscle which result in enhanced response to increasing transmural pressure. The implications of these findings are discussed. PMID- 4017201 TI - Position of the American Heart Association on the use of research animals. A statement for health professionals from a task force appointed by the Board of Directors of the American Heart Association. PMID- 4017202 TI - Abnormal distribution of pulmonary blood flow after the Glenn shunt or Fontan procedure: risk of development of arteriovenous fistulae. AB - Since the Fontan procedure results in low pulsatile pulmonary blood flow similar to that seen in patients with a Glenn shunt, it may also be associated with abnormal distribution of flow to the lower lung lobes and with the development of pulmonary arteriovenous fistulae (PAVF). In 12 patients 0.8 to 4.5 years after Fontan procedure and in 20 patients 0.2 to 18 years after receipt of Glenn shunts we assessed ventilation (with 133Xe) and perfusion (after a peripheral injection of 99mTc-macroaggregated albumin) to compare upper to lower lobe distribution of blood flow with that in a control group. The presence of PAVF was assessed by radionuclide activity in kidneys and the brain and by a two-dimensional echocardiographic contrast study. A decreased upper/lower lobe perfusion ratio was noted in 13 of 20 patients with Glenn shunts (65%) and correlated with the time after surgery (p less than .05). Despite the shorter follow-up period, two of 12 (16%) patients who had undergone the Fontan procedure also had a decreased upper/lower lobe perfusion ratio, and one of these developed right heart failure. Brain and kidney radionuclide counts above control values were observed in all patients with Glenn shunts and in 11 of 12 patients who had the Fontan operation. However, in only five of 20 (25%) patients with Glenn shunts were PAVF confirmed by the two-dimensional echocardiographic contrast study. Three of the five patients with PAVF had Glenn shunts of long duration.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4017203 TI - Programmed ventricular stimulation in survivors of an acute myocardial infarction. AB - The prognostic significance of programmed ventricular stimulation and its usefulness in relation to other forms of invasive and noninvasive testing was evaluated in 150 survivors of acute myocardial infarction. Ventricular tachyarrhythmias of 6 beats or more were induced in 35 (23%) patients. No significant differences existed between patients with inducible ventricular tachyarrhythmias and those without inducible ventricular tachycardia with respect to occurrence of spontaneous ventricular arrhythmias in the acute and early recovery phase of infarction or predischarge exercise-induced ischemia or arrhythmias, severity of coronary artery disease, or degree of left ventricular dysfunction. A higher incidence of inferior myocardial infarction was observed in patients with inducible ventricular tachycardia when compared with those without inducible ventricular tachycardia (66% vs 41%, p less than .01). During a mean follow-up of 10 +/- 5 months (range 2 to 19), there were two sudden deaths, three nonsudden deaths, and two additional patients developed sustained ventricular tachyarrhythmias. There was no significant difference between patients with and those without inducible ventricular tachyarrhythmias with respect to the occurrence of these events. In this study population, a lower mean ejection fraction (p less than .01), the presence of a ventricular aneurysm (p less than .05), and exercise-induced ventricular premature contractions (p less than .05) were predictors of sudden death and of spontaneous ventricular tachycardia. Thus, the findings of this study do not support the hypothesis that the induction of ventricular tachyarrhythmias in patients recovering from acute myocardial infarction identifies a group at high risk for sudden cardiac death. PMID- 4017204 TI - Change in ventricular cavity size: differential effects on QRS and T wave amplitude. AB - Although many factors have been reported to change the R wave amplitude of the electrocardiogram (ECG), few observations have been made of the associated changes in T wave amplitude. We hypothesized that changes in R and T wave amplitude should parallel each other. To test this hypothesis, R and T wave amplitudes were measured in 15 normal subjects during increased and decreased left ventricular dimensions induced by infusion of methoxamine and by Valsalva maneuver, respectively, as well as during changes in the proximity of the left ventricle to the chest wall (i.e., shift in patient position from supine to left lateral position). Simultaneous nine-lead ECGs and two-dimensional-guided M mode echocardiograms of the left ventricle were recorded at rest and under each experimental condition. R wave amplitude increased as the left ventricular lateral wall moved closer to the V5 and V6 electrodes. Alterations in R wave amplitude seen with changes in left ventricular chamber size were primarily caused by radial movement of the left ventricle in relation to the chest wall. Proximity of the left ventricle to the chest wall was therefore a major determinant of R wave amplitude. In contrast, T wave amplitude varied directly with alterations in left ventricular chamber size but was unaffected by changes in proximity to the recording electrode on the chest wall. Left ventricular chamber size, and possibly the associated alteration in endocardial-to-epicardial surface area ratio, appeared to be the major determinants of T wave amplitude. PMID- 4017205 TI - Are right and left ventricular ejection fractions equal? Ejection fractions in normal subjects and in patients with first acute myocardial infarction. AB - Right and left ventricular ejection fractions (RVEF and LVEF) were determined by radionuclide imaging in 37 normal subjects and 37 patients by means of (1) the traditional way of calculating ejection fraction from first-pass time-activity curves of each ventricle generated from a single fixed ventricular region of interest, (2) dual first-pass time-activity curves generated from the end diastolic and end-systolic regions, respectively, and (3) the multigated equilibrium method, also applying separate regions in end-diastole and end systole for each ventricle. Values for RVEF measured by method 2 were significantly higher than values obtained by methods 1 and 3. In normal subjects, the values for RVEF measured by method 2 were equal to the values for LVEF determined by either this method or the equilibrium technique. Methods 1 and 3 had a tendency for underestimation of RVEF, probably because of inclusion of right atrial activity into the right ventricular region of interest. Methods 2 and 3 were applied to measure RVEF and LVEF, respectively, in 153 patients in the second week after first acute myocardial infarction. Among these, 25% had normal ejection fractions, 47% had a decrease in only LVEF, 8% a decrease in only RVEF, and 20% a decrease in both RVEF and LVEF. PMID- 4017206 TI - Altered left ventricular mechanics in patients with valvular aortic stenosis and coarction of the aorta: effects on systolic performance and late outcome. AB - Despite similar degrees of left ventricular systolic hypertension shortening characteristics are usually greater in patients with congenital valvular aortic stenosis (VAS) than in patients with coarctation of the aorta (CoA). We hypothesized that these dissimilarities were caused by differences in myocardial mechanics rather than by alterations in contractile state. Eleven patients with VAS (ages 6 to 41 years) and 11 with CoA were matched for age, body surface area, and peak systolic ejection gradient. Results were compared with data from 22 normal subjects matched for age and body surface area. Echocardiographic tracings of the left ventricle were recorded in conjunction with left ventricular pressure measurements (VAS) or calibrated carotid pulse tracings (CoA and normal subjects). Peak and end-systolic wall stresses as well as left ventricular shortening fraction (% delta D) and rate-corrected velocity of fiber shortening (Vcfc) were calculated. No differences for left ventricular dimensions, heart rate or peak wall stress were present. Ventricular peak systolic pressures and wall mass were higher for the patients with VAS or CoA than for the normal subjects (p less than .001). These parameters did not differ between the VAS and CoA groups. The patients with VAS had higher % delta D and Vcfc than either the CoA or normal groups (p less than .01). Afterload, as quantified by end-systolic stress, was 41% lower than normal for the patients with VAS (p less than .001) and 13% higher than normal for those with CoA (p less than .05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4017207 TI - Electrophysiologic and antiarrhythmic effects of sotalol in patients with life threatening ventricular tachyarrhythmias. AB - Sotalol is a unique beta-blocker that lengthens cardiac repolarization and effective refractory period (ERP). Its efficacy after intravenous (1.5 mg/kg) and oral (160 to 480 mg bid) administration was therefore evaluated in 37 patients with refractory recurrent ventricular tachycardia/fibrillation (VT/VF). Thirty five patients, 33 with inducible VT/VF, underwent electrophysiologic testing. Intravenous sotalol lengthened the ERP in the atrium (+24.6%, p less than .01), atrioventricular node (+24.9%, p less than .01), and ventricle (+14.9%, p less than .01). It also significantly lengthened sinus node recovery time, corrected QT interval (QTc), and the AH interval, but not the HV interval. Sotalol prevented reinduction of VT/VF in 15 patients (45.5%). Twenty-five of the 33 patients (15 with positive results of electrophysiologic tests; 10 with negative results) were given oral sotalol. The drug was ineffective in seven (26.9%) and aggravated arrhythmia in one (3.8%). In four patients sotalol was withdrawn because of side effects; arrhythmias recurred late in two (7.7%). Eleven patients (42.3%) have continued on oral sotalol over a mean follow-up period of 9.2 +/- 8.6 months. Sotalol reduced (n = 21) total premature ventricular complex (PVC) count on the Holter electrocardiogram by 73% (p less than .01), paired PVCs by 89% (p less than .01), and beats of ventricular tachycardia by 95% (p less than .01). In 52% (n = 11), total reduction in PVCs was at least 85%, and incidence of paired and tachycardiac beats was reduced at least 90% (group A). In the remainder (n = 10), PVC suppression was not significant (group B). Group A included nine patients with nonreinducible VT/VF and two in whom it was reinducible; in group B, eight of 10 patients had reinducible VT/VF. The difference between the two groups (Fisher exact test) was significant (p less than .01). The prevention of reinduction of VT/VF by intravenous sotalol and suppression of spontaneously occurring arrhythmias by the oral drug were both predictive of long-term drug efficacy. Sotalol is a significant advance in the short- and long-term management of life-threatening ventricular tachyarrhythmias. PMID- 4017208 TI - Metabolic fate of radioiodinated heptadecanoic acid in the normal canine heart. AB - To clarify the metabolic fate of radioiodinated heptadecanoic acid in myocardium, the time course and distribution of the radioactivity over 131I-heptadecanoic acid, free radioiodide, and various lipids (with incorporated iodoheptadecanoic acid) were determined in normal canine myocardium. In 10 dogs seven biopsy specimens were taken over 30 min after injection of 131I-heptadecanoic acid. The radioactivity in the specimens increased until the fifth minute and decreased thereafter, with a half-time of 36 min. In the fifth minute, 61% of the radioactivity was free iodide, and its curve paralleled the curve of the total radioactivity. As early as the first minute 131I-heptadecanoic acid activity was reduced to 14% and decreased further. Activity of radioiodinated phospholipids, (mono, di, tri)-glycerides, and cholesterol-esters remained constant after an initial increase. These results indicate that immediately after uptake, 131I heptadecanoic acid is either metabolized, liberating the radioiodide, or stored in lipids. Because the activity of radiolabeled lipids remained constant during the study period and because iodide activity paralleled the total activity in biopsy specimens, it is concluded that in normal myocardium, washout of free radioiodide determines the elimination rate as observed during a scintigraphic study. Thus the elimination rate cannot be related to the beta-oxidation rate as previously supposed. PMID- 4017209 TI - Angle dependence of ultrasonic backscatter in arterial tissues: a study in vitro. AB - The object of this study was to obtain quantitative data on the angle dependence of reflected ultrasound signals in freshly excised normal human arterial walls and those with different degrees of atherosclerotic involvement (fatty, fibrofatty, fibrous, or calcified). Fifteen specimens were evaluated in each pathologic subset. The backscatter coefficient (BS, expressed as cm-1 X steradians -1), measured at the single frequency of 10 MHz, was evaluated at a normal angle of incidence of the interrogating beam to the tissue sample and over an angular span of 60 degrees (+/- 30 degrees around normal incidence, 2 degree steps). BS measured at normal incidence separated normal (10(-2) X 0.155 +/- 0.018; mean +/- SE) from fibrofatty (10(-1) X 0.0103 +/- 0.008), fibrous (10(-1) X 0.182 +/- 0.016), and calcified (0.202 +/- 0.016) specimens; normal and fatty (10(-3) X 0.759 +/- 0.142) and fibrofatty and fibrous samples could not be distinguished from each other in a statistically significant way. Angular scattering measurements identified two patterns: A "directive" pattern, characterized by a strongly angle-dependent BS that falls abruptly when the beam is moved slightly away from normal incidence. This pattern was typical of calcified, fibrous, and less markedly, fibrofatty and normal samples. A "nondirective" pattern, characterized by a BS that is not significantly angle dependent and fluctuates throughout the entire angular range. This was typical of fatty samples. PMID- 4017210 TI - Effects of unilateral stellate ganglion stimulation and ablation on electrophysiologic changes induced by acute myocardial ischemia in dogs. AB - We recorded direct-current extracellular electrograms simultaneously from 60 left ventricular epicardial sites in 38 alpha-chloralose-anesthetized dogs during repeated, 5 min coronary arterial occlusions. In each dog recordings made during control occlusions were compared with those made in occlusions after, or during, the following interventions on the sympathetic nervous system: left stellate ganglion stimulation, left stellectomy, right stellectomy, and clamping the abdominal aorta with intact sympathetic nerves to induce a rise of blood pressure equal to that present during left stellate stimulation. Heart rate was kept constant. Measurements included determination of TQ segment potentials and times of local activation. After 2 min of ischemia, the degree of TQ segment depression was increased by left stellate ganglion stimulation and was decreased by both left stellectomy and clamping the aorta. Also, the area showing negative TQ potentials, indicating decreased resting membrane potentials, was enlarged by both left stellate stimulation and right stellectomy and reduced by left stellectomy. No differences were found in the results of experiments in which the left anterior descending coronary artery was occluded and those in which the circumflex branch was occluded. Left stellate stimulation significantly improved conduction within the ischemic zone. No evidence was found to suggest that the arrhythmogenic effects of left stellate stimulation and of right stellectomy, confirmed in the present study, resulted from an increased likelihood for reentry in the subepicardium of the ischemic zone. PMID- 4017211 TI - Electrophysiologic and anatomic basis for fractionated electrograms recorded from healed myocardial infarcts. AB - The electrophysiologic and anatomic basis for fractionated electrograms were investigated in superfused epicardial preparations from infarcted canine hearts. Fractionated bipolar electrograms were frequently recorded in preparations from infarcts 2 weeks to 18 months old but only rarely in preparations from 5-day-old infarcts. The fractionated electrograms were not caused by movement artifacts. They were not associated with depressed transmembrane resting or action potentials (which were found in the 5-day-old infarcts), but rather transmembrane potentials recorded in the vicinity of the bipolar electrodes were normal. Despite the normal transmembrane potentials, activation time in regions where fractionated electrograms occurred was prolonged. However, prolonged activation time by itself did not cause fractionation, since fractionated electrograms were not recorded from normal preparations in which conduction was markedly slowed by a superfusate containing 16 mM potassium and epinephrine. Unipolar electrograms recorded with glass microelectrodes (tip size 1 to 5 microns) showed that activation in regions where fractionated electrograms were recorded was inhomogeneous. Prepotentials were found preceding the upstrokes of some action potentials in regions where double potentials were recorded, suggesting the possibility of electrotonic transmission across high resistance or inexcitable gaps, but no electrotonic potentials were seen in regions with multicomponent fractionated electrograms. Fractionated electrograms were recorded in regions where infarct healing caused wide separation of individual myocardial fibers while distorting their orientation. The anatomic changes probably caused slow and inhomogeneous activation. PMID- 4017212 TI - Catheter-mediated electrical ablation of the posterior septum via the coronary sinus: electrophysiologic and histologic observations in dogs. AB - In a series of 12 dogs, the electrophysiologic and histologic effects of a single damped sine-wave shock delivered via standard electrocatheters to the region of the coronary sinus orifice were investigated. Six dogs received 200 J and six received 360 J of stored energy. The shock was delivered to two consecutive proximal poles of a standard quadripolar catheter positioned at the coronary sinus orifice and connected to the positive output (anode) of a defibrillator. A disc electrode positioned on the anterior chest wall served as the cathode (negative pole). During the shock, voltage and current were recorded. Electrophysiologic testing was done before and 4 weeks after the shock. At 4 weeks, animals were killed and serial sections of the atrioventricular groove and conduction system were performed. No significant long-term change in atrioventricular conduction, spontaneous or induced atrial or ventricular arrhythmias was observed. However, transient atrioventricular block was seen in five and idioventricular rhythms in six animals in the short term. No persistent electrocardiographic changes were observed, and no sudden deaths occurred. Microscopically, transmural injury at the anulus proper or basilar ventricular epicardium was inconstant and infrequent. However, transmural atrial injury at the level of the coronary sinus was produced over a 10 +/- 5 mm length with the 200 J shock and a 21 +/- 6 mm length with the 360 J shock. Neither coronary artery injury nor damage to the conduction system was seen and cardiac tamponade did not occur. However, localized intramural atrial rupture of the coronary sinus wall (on the endocardial aspect only) was observed in each dog, consistent with barotrauma. With the present technique, atrial injury potentially capable of blocking the effects of accessory pathway conduction could be produced without other electrophysiologic alterations or complications. Injury to the anulus proper (and therefore to any accessory pathway per se) is probably unlikely. Barotrauma may play a significant role in the type of injury observed in this study. PMID- 4017213 TI - Interruption of sympathetic and vagal-mediated afferent responses by transmural myocardial infarction. AB - We have demonstrated previously that sympathetic and vagal afferents travel in an apical-to-basal course in the heart, and can be stimulated selectively with epicardial applications of bradykinin and nicotine, respectively. In this study we tested the hypothesis that transmural myocardial infarction interrupts sympathetic and vagal afferent fibers traveling through the infarction and produces regions of afferent denervation in areas apical to the infarction. In open-chest, chloralose-anesthetized dogs, transmural myocardial infarction was created by embolizing a diagonal branch of the left anterior descending coronary artery with a vinyl latex solution that was injected directly into the artery and hardened rapidly. The transmural nature of the infarction was verified by the nitro blue tetrazolium staining technique for dehydrogenase enzymes. Epicardial applications of bradykinin (5 micrograms) and nicotine (50 micrograms) were used to stimulate chemically sensitive sympathetic and vagal afferent nerve endings, respectively. Twenty-nine dogs were studied before and 90 min after creation of transmural myocardial infarction. In 20 dogs, epicardial bradykinin applied before production of transmural myocardial infarction produced a maximal pressor response of 13 +/- 3 mm Hg 40 sec after application (p less than .01 vs preapplication values), while topical nicotine produced a maximal depressor response of 14 +/- 2 mm Hg (p less than .01 vs preapplication values) 20 sec after application at all sites tested. Ninety minutes after production of transmural myocardial infarction, epicardial sites basal to the infarction continued to respond normally to both drugs, while sites within the area of infarction and apical to the area (noninfarcted myocardium) no longer showed a pressor response to topical bradykinin or a depressor response to topical nicotine.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4017214 TI - Left ventricular ejection fraction after acute coronary occlusion in conscious dogs: relation to the extent and site of myocardial infarction. AB - The change in left ventricular radionuclide ejection fraction after acute occlusion of the left anterior descending (LAD) or circumflex (LC) coronary artery was compared with the ultimate histologic extent of myocardial infarction in conscious dogs. The acute change in ejection fraction correlated with size of infarction in 14 dogs with occlusions of the LAD coronary artery (r = .89, y = 1.12x + 14.2) and in 27 dogs with occlusions of the LC coronary artery (r = .71, y = 0.73x + 7.9); the slope of the regression equation was greater (p less than .05) for those with LAD than for those with LC occlusions. Multivariate analysis revealed no independent contribution of left ventricular weight, the subendocardial extent of infarction, or change in heart rate to the acute change in ejection fraction. These data indicate that the decrease in ejection fraction after coronary occlusion is determined primarily by the size of the ischemic area, which also determines size of infarction. In dogs instrumented over a long term, infarcts in the LAD myocardial distribution result in greater decreases in ejection fraction than infarcts of comparable size in the LC distribution. PMID- 4017216 TI - The superiority of maximum fiber elastance over maximum stress-volume ratio as an index of contractile state. AB - The end-systolic pressure-volume relationship has been used as a load-independent measure of ventricular pump performance. Since comparisons of load between ventricles of different size and thickness may be more accurately made with measurements of wall stress than with those of pressure, the end-systolic stress volume relationship at one or more levels of end-systolic stress has been used to estimate contractile function in hypertrophied ventricles. Linear regression of end-systolic stress against end-systolic volume for differently loaded beats has a slope termed maximum fiber elastance (fiber Emax) and a volume intercept termed Vo; the maximum stress-volume ratio (MSVR) for a single beat is an approximation of fiber Emax but assumes Vo = 0. However, the influence of preload, afterload, and inotropic state on these indexes has not been examined. We therefore studied the stress-volume relationship in seven open-chest dogs instrumented with ultrasonic crystals and micromanometers. Postextrasystolic potentiation (PESP) increased both the MSVR (5.7 +/- 1.83 vs 4.85 +/- 1.43 at control, p less than .05) and fiber Emax (13.93 +/- 3.24 vs 9.24 +/- 2.15 at control; p less than .05). Augmentation of preload by infusion of dextran, with the use of nitroprusside to maintain afterload relatively constant, did not significantly influence either the MSVR or fiber Emax. Vo was not significantly influenced by PESP, but was shifted to higher values by augmentation of preload (17.5 +/- 14.8 vs 13.9 +/- 11.1 ml at control; p less than .05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4017215 TI - Patterns of myoglobin release after reperfusion of injured myocardium. AB - Myoglobin is an intracardiac protein that is released into the blood after myocardial injury and is then cleared rapidly by the kidneys. This study was undertaken to determine whether successful reperfusion of damaged myocardium could be assessed by examination of blood myoglobin concentration-time patterns. After release of a 2 hr occlusion of the mid left anterior descending coronary artery in 11 dogs that had been instrumented over the long term, immunoreactive arterial plasma concentration of myoglobin, [Mb], rose rapidly to a peak within 25 +/- 2(SEM) min (range 20 to 40). Individual peaks were three to 165 times the myoglobin levels immediately before release of the occlusion. Myoglobin was cleared rapidly from plasma, falling to one-half its peak level 38 +/- 3 min after the peak. Similarly well-defined peaks in [Mb] were evident in plasma from the great cardiac vein (GCV), with a mean time to peak of 16 +/- 2 min and a magnitude of two to 177 times prerelease values. In contrast, arterial and GCV creatine kinase activity-time curves showed less defined peaks and they occurred later and with more variability (60 to 330 min after reperfusion). In nine patients with acute infarction, successful coronary artery reopening was also accompanied by a sharp four- to sixteenfold rise in plasma [Mb] within 1 to 2 hr. Elevations in plasma creatine kinase were slower and more prolonged, peaking at 2 to 18 hr.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4017217 TI - Effect of heart rate on the canine end-systolic pressure-volume relationship. AB - Although the rate dependence of isolated muscle contractility is well known, the ventricular end-systolic pressure-volume relationship (ESPVR) has been reported to be insensitive to heart rate. To resolve this contradiction, we used an isolated, ejecting canine heart preparation perfused at a constant coronary arterial pressure. Heart rate was changed from 60 to 200 beats/min in steps of 20 beats/min. At least 10 pressure-volume loops under different filling pressures were obtained at each heart rate in each of six hearts. Over a heart rate range from 60 to 120 beats/min, the slope of the ESPVR (Ees) increased significantly from 3.5 +/- 0.4 (SE) to 5.3 +/- 0.6 mm Hg/ml. In the range between 120 and 180 beats/min there was little change in Ees (5.3 +/- 0.6 to 5.4 +/- 0.6 mm Hg/ml), but at 200 beats/min Ees increased slightly to 5.7 +/- 0.5 mm Hg/ml. The volume axis intercept (V0) of the ESPVR changed little over the range of heart rate from 60 to 160 beats/min (10.2 +/- 2 ml to 9.4 +/- 1.3 ml) but increased to 15.2 +/- 1.2 ml at a rate of 200 beats/min. The change in ESPVR with increase in heart rate from 60 to 120 beats/min (i.e., increase in Ees without change in V0) is the same as those seen with a positive inotropic intervention with calcium or cathecholamines, whereas the V0 changes over the range from 160 to 200 beats/min is similar to those seen with regional ischemia.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4017218 TI - A potential method of correcting intracavitary left ventricular filling pressures for the effects of positive end-expiratory airway pressure. AB - Based on the observation that positive end-expiratory airway pressure (PEEP) causes comparable increments in intrapericardial and right-sided intracardiac pressures, we hypothesized that intracavitary left ventricular filling pressures measured in the presence of PEEP can be corrected for increased intrathoracic pressure by subtracting the effects of PEEP on intracavitary right ventricular filling pressures. Ventricular function curves (aortic blood flow vs intracavitary left ventricular end-diastolic pressure [LVEDP]) were generated with and without 15 cm of water of PEEP in eight dogs. All curves were shifted to the right by PEEP (i.e., intracavitary LVEDP was higher for any submaximal level of aortic blood flow). However, when pressures measured in the presence of PEEP were "corrected" by subtracting the corresponding increment in intracavitary right ventricular end-diastolic pressure caused by PEEP at each level of ventricular filling, control and corrected PEEP data points appeared to fall on the same curve in five dogs, and differed only slightly in three dogs. Mean control and corrected PEEP curves derived by averaging polynomial regression coefficients for each condition differed significantly from uncorrected PEEP curves (p less than .05), but not from each other. Analogous curves based on mean left atrial pressure were corrected equally well by subtracting the effects of PEEP on mean right atrial pressure. We conclude that the increments in intracavitary right heart filling pressures caused by PEEP can be used to correct intracavitary left heart filling pressures for the effects of PEEP on intrathoracic pressure. PMID- 4017219 TI - Diminished stroke volume during inspiration: a reverse thoracic pump. AB - In 12 conscious dogs, a three-dimensional array of pulse-transit ultrasonic transducers was used to measure left ventricular anterior-posterior minor, septal free wall minor, and basal-apical major diameters. Matched micromanometers measured left ventricular, right ventricular, and intrapleural pressures. Electromagnetic ascending aortic blood flow and right ventricular transverse diameter were measured in five of the dogs. A major cause of the inspiratory decline in stroke volume in this preparation appeared to be reflex tachycardia and autonomic changes associated with inspiration. However, when heart rate was controlled by atrial pacing or pharmacologic autonomic attenuation (propranolol and atropine), stroke volume still decreased around 10%, with an inspiratory decrease in pleural pressure of 10 mm Hg. Based on the measurements of ventricular dimension, venous return to the right ventricle appeared to be augmented significantly during inspiration and the transient increase in right ventricular volume was associated with leftward interventricular septal shifting and altered diastolic left ventricular geometry. However, left ventricular end diastolic volume was changed minimally, implying that alterations in preload were not important. Moreover, transmural left ventricular ejection pressure, calculated as intracavitary minus pleural pressure, was not significantly changed, and it seemed that neither pressure nor geometric components of afterload were altered significantly by inspiration. The inspiratory fall in left ventricular stroke volume correlated best with the decline in intracavitary left ventricular ejection pressure referenced to atmospheric pressure. It is hypothesized that during ejection, left ventricular pressure referenced to atmospheric pressure is the hydraulic force effecting stroke volume and that the decline in this effective left ventricular ejection pressure is responsible for the inspiratory fall in stroke volume through a reverse thoracic pump mechanism. PMID- 4017220 TI - Occupational lead exposure: studies in two brothers showing differential susceptibility to lead. AB - Unexpected differences in clinical and biochemical findings in two brothers occupationally exposed to the same source of lead for dissimilar lengths of time are presented. Only the brother with the shorter period of lead exposure was anemic and afflicted by nausea, vomiting, abdominal colic and arthralgia. His urinary PBG output yielded the high orders of magnitude found in acute intermittent porphyria in relapse. Prior to administration of a single dose of EDTA (1 g of the calcium disodium salt given intravenously in 325 mL 0.15 mol/L NaCl), his blood lead levels averaged 3.6 mumol/L. The amount of chelatable lead retrieved from his urine, 31 mumol/day, was more than twice that found in his asymptomatic counterpart who was exposed to lead for 13 months and whose pre-EDTA blood lead levels averaged 4.0 mumol/L. Not only the activity of delta aminolaevulinic acid dehydratase, but also that of uroporphyrinogen I synthetase, was markedly inhibited by lead in red cells of both brothers. These activities were restored to normal levels in vitro by addition to the assay system of zinc and dithiothreitol. This ruled out a coexisting genetic deficiency of either enzyme. The anemia of the symptomatic brother with the shorter period of lead exposure was alleviated by folic acid, 15 mg/day. The differences in findings between the two brothers point to differential susceptibility to lead and illustrate the extent to which symptomatic lead poisoning may mimic biochemical and clinical features of the acute porphyrias. PMID- 4017221 TI - The effect of fluoride on nephrocalcinosis in rats. AB - To investigate the effects of fluoride on soft tissue calcification, female weanling rats were fed a nephrocalcinogenic diet and NaF in drinking water over a 4 week period. The diet contained adequate Ca (0.5%) and high phosphorus (1.0%, P). The nephrocalcinosis is attributed to the relatively low dietary Ca/P ratio since addition of Ca to provide a Ca/P ratio of 2.0 prevents kidney calcification. With NaF in drinking water at levels of 1.19 to 4.76 mmol/L kidney calcification was decreased from 127 +/- 24 to 17.3 +/- 1.7 mumol/g wet weight, with no significant differences over this dose range. With the increasing NaF doses, serum F, at 4 weeks, increased from 4.4 +/- 0.8 to 36.5 +/- 6.0 mumol/L compared to untreated F levels of 1.2 +/- 0.1 mumol/L. Bone histology showed no evidence of F stimulation with any of these NaF doses. Previously reported work has shown that, for weanling rats on this diet, greater than 4.8 mumol/L NaF in drinking water is required to produce histological fluorosis within 5 weeks. To inhibit kidney calcification, NaF treatment must be maintained throughout the 4 week study period since calcification occurred if NaF was withheld over either the initial or final 2-week period. These findings indicate a possible therapeutic value of NaF, clinically, in the prevention of soft tissue calcification. PMID- 4017222 TI - Comparison of three methods for the elimination of the labile fraction of HbA1. AB - Three different procedures were used to remove the "labile" fraction in the chromatographic quantitation of hemoglobin A1 (HbA1) by a minicolumn assay: (a) preincubation of the erythrocytes at 37 degrees C in isotonic saline for 4 h, (b) preincubation in the presence of semicarbazide-aniline at pH 5.0 for 30 min, and (c) preincubation in acetate buffer at pH 5.5 for 30 min. The results show that the two latter methods are not only more rapid but are also slightly more effective. The use of the acetate buffer is preferred because this reagent is more easily prepared and also because the presence of semicarbazide and aniline did not markedly accelerate the dissociation of Hb pre-A1c at pH 5.5. The procedure relies simply on the greater instability of Schiff base in acidic solution. There is a significant correlation between the "labile" fraction and the plasma glucose concentration at sampling time. The results support the view that the elimination of the "labile" precursor is essential to preserve the utility of the assay. PMID- 4017223 TI - A sensitive fluorometric assay for serum monoamine oxidase with kynuramine as substrate. AB - The detailed procedure of a new sensitive fluorometric assay for human serum monoamine oxidase (MAO) with kynuramine as substrate is described. The data on its reproducibility, stability, correlation with another method, and serum MAO levels for 150 healthy subjects and 205 patients with various diseases, are presented to support the usefulness of this method. Since our method is much simpler and more sensitive than other methods conventionally used, we can recommend it for routine clinical investigation. PMID- 4017224 TI - [Evaluation of urinary density by AMES reagent strips and comparison to the density determined by refractometry and urinary osmolarity]. PMID- 4017225 TI - Continuous-flow enzymic determination of serum total and high density lipoprotein cholesterol using microlitre sample volumes. AB - We determine serum total cholesterol and high-density lipoprotein cholesterol (HDL-C) using a modified Technicon Auto Analyzer II-BMC enzymic system. The method uses 25 microL of sample (serum or supernate) for cholesterol determinations. Pooled serum which was calibrated indirectly against CDC's Abell Kendall method was used for standardization. Accuracy and precision for total cholesterol determinations are comparable to those obtained using a modified Technicon AAII method. Coefficients of variation for the determination of HDL-C prepared by heparin/Mn++ precipitation are 6.4% and 4.6% at concentration levels of 0.70 mmol/L and 0.94 mmol/L respectively. The interchangeable use of deionized distilled water and 0.15 mol/L NaCl solution for dilution of samples analyzed by the micro method is shown to produce significantly different cholesterol estimates. The reduced reagent volumes significantly lower the cost of cholesterol determinations. The system is simple, inexpensive and yields reliable cholesterol and HDL-C results. PMID- 4017226 TI - The presence of glycosylated, biologically active chorionic gonadotropin in human liver. AB - Whole extracts of normal human liver contain hCG-like material as determined by radioimmunoassay using antibodies to the beta subunit of the hormone. However, the extracts are biologically inactive, when analyzed by the in vitro rat Leydig cell assay for steroidogenesis. When subjected to Concanavalin-A-Sepharose chromatography, the radioimmunoassayable material was entirely lectin-bound. After elution with methyl-alpha-D-glucopyranoside, the lectin-bound fractions now displayed biological activity. PMID- 4017227 TI - The Laboratory Information System (LIS): I-Application to the clinical chemistry laboratory. AB - The Laboratory Information System (LIS) was designed as a "turn-key" system. The main functions are operated interactively on a mini-computer which gives the laboratory complete control over daily processing. Collection of results from automated analyzers is accomplished via a micro-computer/micro-processor network. Links are provided with a central main frame computer for immediate patient identification and historical data processing. LIS is designed to manage all the operations involved in laboratory activities. The system has 14 major functions: registration of test requests, production of specimen collection sheets and identification labels, confirmation of specimen collection, production of aliquot labels, workload inquiry, production of worksheets, manual entry of test results, automated entry of test results, results inquiry, preliminary report, final report, daily activities reports, statistical reports, billing. System security is provided along three directions: data entry validation, system access control, and memory protection. The main advantages of LIS are: reduced clerical work, better evaluation of workload, faster communication, improvement of information given to the clinician: adapted reference values, interpretation, comments, improved retrieval operations, faster billing. PMID- 4017228 TI - A function for estriol during human pregnancy--a hypothesis. AB - It has been hypothesized that large amounts of estriol (E3) are produced during human pregnancy to ensure a quiescent uterus during prelabour pregnancy by combining with most of the myometrial nuclear receptors, leaving an inadequate number for a stimulatory estradiol (E2) concentration. It is further hypothesized that the amount of E3 formed is controlled by the amount of E2 present. During labour this control is lost, which together with an increased E2 (plus or minus a simultaneous drop in E3) production permits labour. Two of the seven pieces of evidence offered in support of this hypothesis were carried out in the author's laboratory. These are: 1. Urinary assays by two methods, one for total estrogens and one for the fractionated classical estrogens revealed that while the ratio (formula; see text) varies from patient to patient, for any one patient it remains markedly constant, especially during the second half of pregnancy. 2. Pieces of myometrium removed at cesarean delivery and assayed for their nuclear estrogen content revealed an E3/E2 ratio of 1.7 when the cesarean was an elective one (and therefore with a quiescent uterus) but reduced to 0.65 when the cesarean was performed after labour had started. The relationship between these two pieces of evidence and five from the literature with the hypothesis are discussed. PMID- 4017229 TI - Stimulation of 5-aminolevulinic acid metabolism by uroporphyrinogen I in rat liver homogenate. AB - The effect of excess uroporphyrinogens I and III, coproporphyrinogen III, and the corresponding porphyrins, on the rate of 4-14C-5-aminolevulinic acid (ALA) metabolism was studied. Experiments were performed with mitochondria-free rat liver homogenates prepared from normal rats. The consumption of labelled 5 aminolevulinic acid was followed by measuring its level in aliquots removed at intervals. The pattern of porphyrinogen synthesis was examined by high pressure liquid chromatography. Only uroporphyrinogen I had an effect; it increased the rate of conversion of ALA and porphobilinogen (PBG) to porphyrinogens. Chromatographic analysis revealed increased synthesis of uroporphyrinogen and heptacarboxylic porphyrinogen. It is believed that this mechanism might explain the lack of ALA and PBG accumulation in erythropoietic porphyria and porphyria cutanea tarda, and the absence of acute porphyria attacks in these conditions. PMID- 4017230 TI - Combined liquid chromatography/radioimmunoassay with improved specificity for serum digoxin. AB - This method for assaying digoxin in serum with improved specificity combines small-column extraction of serum, "high-performance" liquid chromatography, and RIA of the eluted fractions. Analytical recoveries of 1.0, 0.5, and 0.1 microgram/L standards were 95%, 93%, and 84%, respectively. The CVs for duplicates and replicates of sera with values of 0.5 to 1 microgram/L were 4 to 6%. Fifty-nine sera from 50 patients receiving digoxin were so studied. All digoxin metabolites appear to cross react with antibody to digoxin to various degrees. The most polar metabolites were quantitatively the most important, their average cross reactivity being 33%. For eight patients the value for digoxin by the present method was less than 60% of the RIA value. Sera from nine patients not taking digoxin but with falsely high digoxin values were also studied by the present method. The digoxin peak was well resolved from those for (a) digoxin metabolites (except dihydrodigoxin), (b) digitalis-like factors in neonates and in patients with renal failure or combined hepatic and renal failure, and (c) two cross reacting drugs and their metabolites. PMID- 4017231 TI - Volatile organic compounds in exhaled air from patients with lung cancer. AB - Using a specially developed breath collection technique and computer-assisted gas chromatography/mass spectrometry (GC/MS), we have identified in the exhaled air of lung cancer patients several volatile organic compounds that appear to be associated with the disease. The GC/MS profiles of 12 samples from lung cancer patients and 17 control samples were analyzed by using general computerized statistical procedures to distinguish lung cancer patients from controls. The selected volatile compounds had sufficient diagnostic power in the GC/MS profiles to allow almost complete differentiation between the two groups in a limited patient population. PMID- 4017232 TI - Assessment of corpus luteum function by direct radioimmunoassay for progesterone in blood spotted on filter paper. AB - In this specific, direct RIA for progesterone in capillary blood dried on filter paper, progesterone is eluted, with phosphate buffer containing bovine serum albumin, from 5.9 microL of blood dried on 5.0-mm (diameter) discs of filter paper. The eluate is assayed, with 125I-labeled progesterone-11 alpha-glucuronyl tyramine as tracer, with separation by a double-antibody solid-phase technique. The sensitivity of the assay is 4.7 pg per tube, corresponding to 2.5 nmol per liter of blood. Within- and between-batch CVs averaged 7.0 and 9.2%, respectively, over the working range of the assay (4.5-64 nmol/L). Concentrations of progesterone in blood spots (y) correlated well with those in serum (x) as measured by an established direct RIA (Clin Chem 28:1314, 1982): y = 0.430x - 2.44 (r = 0.972, n = 104). Progesterone is stable in the blood spots for at least 15 weeks at 25 degrees C. The convenience of multiple sampling of blood by finger prick and the simplicity of the assay make this approach useful in investigating serial progesterone concentrations in outpatients. PMID- 4017233 TI - Radioimmunoassay of active pancreatic enzymes in sera from patients with acute pancreatitis. I. Active carboxypeptidase B. AB - Previous studies have suggested that measurement of active enzymes in relation to proenzymes in serum of patients with pancreatitis may reflect the degree of zymogen activation in the gland. Here we describe the first single-tube assay for an active form of a pancreatic enzyme that is ordinarily synthesized as a proenzyme. Human procarboxypeptidase B, which we purified to near homogeneity, is approximately 13 000 Da larger than the active enzyme (EC 3.4.17.2). Antibodies specific for active carboxypeptidase B were obtained by affinity chromatography of anti-carboxypeptidase B antisera on a gel containing procarboxypeptidase B, then used to develop a single-tube radioimmunoassay for measuring active carboxypeptidase B in serum. Using this assay, we were able to detect, for the first time, active carboxypeptidase B in sera from patients with acute pancreatitis. Preliminary data show a correlation between the serum concentrations of active carboxypeptidase B and those of active trypsin complexed with serum inhibitors, but no correlation with serum amylase values. PMID- 4017234 TI - Radioimmunoassays for type III procollagen amino-terminal peptides in humans. AB - Use of radioimmunoassay for the amino-terminal propeptide of type III procollagen for monitoring fibrotic processes in humans has been frustrating because of the nonparallel relation between results for the standard bovine antigen and human serum samples. In the radioimmunoassays I developed for this propeptide and its monomeric Col 1 domain, based on use of antigens from humans, serum samples generated less-steep inhibition curves than did the standard antigen in the propeptide assay; in the Col 1 assay, however, serum and urine samples both generated inhibition curves having the same slope as that generated with the standard Col 1 peptide. Concentrations of human fragment Col 1 in serum samples as measured with the Col 1 assay were usually double those obtained with the human propeptide assay, which in turn were two- to threefold those obtained with the bovine antigen assay. In control subjects and alcoholic cirrhotics the concentrations of antigen in urine and the daily excretion rates as measured with the assay for human Col 1 exceeded those reported previously. The presence of different antigen forms was demonstrated with both assays by gel-filtration analysis of serum and urine samples. The assay for human Col 1 should be suitable for routine clinical chemical use. PMID- 4017235 TI - Amino acid concentrations in plasma and skeletal muscle of patients with acute hemorrhagic necrotizing pancreatitis. AB - We measured amino acid concentrations in plasma and skeletal muscle of three groups of patients with acute hemorrhagic pancreatitis: (a) patients without secondary organ lesions, (b) patients also suffering from kidney damage, and (c) patients in whom the pancreatitis was accompanied by sepsis and multiple organ failure. In all three groups, especially the third group, the amino acid concentrations in both plasma and muscle were below normal. Glutamine was only 14% of normal in muscle tissue of the third group. Onset of renal insufficiency was indicated by increasing values for 3-methylhistidine and cystathionine; multiple organ failure, by increased concentrations of methionine and phenylalanine in plasma. The low amino acid concentrations of patients with acute pancreatitis can be explained as a combined effect of semistarvation and hypercatabolism. Changes in the plasma concentrations of amino acids did not reflect necessarily the concentrations in muscle tissue. PMID- 4017236 TI - Spectrophotometric investigation of sensitive complexing agents for the determination of zinc in serum. AB - Of two sensitive complexometric reagents for the colorimetry of serum zinc that we investigated, one, 2-(5-bromo-2-pyridylazo)-5-diethylaminophenol (Br-PADAP), was found to be a potentially useful compound for trace-metal determinations. It has a high molar absorptivity (120 000 L mol-1 cm-1) but is not convenient to use because it is not very soluble in water. The other reagent, a related pyridylazo compound, is 2-(5-bromo-2-pyridylazo)-5-(N-n-propyl-N-3-sulfopropylamino)phenol (5-BR-PAPS). It seems better suited for use in routine zinc determinations because, besides being water soluble, it has a higher molar absorptivity, 130 000 L mol-1 cm-1. Results by the proposed method developed with 5-Br-PAPS correlated well with those by atomic absorption spectrophotometry. The between-run CV for control sera was less than 5%; the within-run CV (same controls) was less than 4%. PMID- 4017237 TI - An anion-exchange chromatographic method for measuring bilirubin covalently bound to albumin. AB - After alkalinizing the diazo products of serum bilirubins, we apply them to a column of anion-exchange resin. The azodipyrroles derived from unconjugated and sugar-conjugated bilirubins, as well as from one half of the tetrapyrrole covalently linked to albumin ("Bil-Alb"), are anionic and protein-free and adsorb to the resin. The other half of the azo product of Bil-Alb, with absorptivity similar to that of the protein-free azodipyrroles, remains attached to albumin (Clin Chem 28:629-637, 1982) and passes through the resin unadsorbed. The color of the eluate correlates directly with the original amount of Bil-Alb present. Estimates of authentic Bil-Alb by the method agree with those by a Jendrassik Grof total-bilirubin method (in mg/L: intercept = -0.8, slope = 1.005, r = 0.999) and by liquid chromatography (Clin Chem 29:800-805, 1983) (n = 52, intercept = 5.2, slope = 0.724, r = 0.965). The CV of the method for serum with Bil-Alb of 99.4 mg/L was 3.8% (n = 8). PMID- 4017238 TI - Can potentially infectious specimens containing hepatitis B virus be identified on the basis of their biochemical profile? AB - The potential infectivity of 1129 randomly selected plasma specimens was directly assayed by hepatitis B virus (HBV) DNA dot-hybridization. Presence or absence of HBV was then correlated with a biochemical profile of 20 common analytes obtained on these same specimens. We found that potentially infectious specimens could not be identified on the basis of any combination of simple biochemical tests; indeed, the infectious specimens were more "normal" in some tests of liver function than were the non-infectious specimens. PMID- 4017239 TI - Preparation and use of serum-based material as control and calibrator in evaluating ion-selective electrodes for calcium. AB - We analyzed 93 sera and 81 whole-blood samples, plus several aqueous materials and one serum-based material as controls, with two analyzers for ionized calcium (Radiometer ICA 1 and AVL 980). On 16 days, comparisons of results for patients' samples were good, with nearly all between-instrument differences (delta Ca2+) of samples being within 0.04 mmol/L. On 12 days, comparisons were mediocre, with the delta Ca2+ of samples usually 0.04 to 0.10 mmol/L. The control material that most consistently indicated the direction and magnitude of the delta Ca2+ of patients' samples was the serum-based control. Adjustment of results for samples from patients, based on the delta Ca2+ of the serum control on the same day, substantially improved comparisons between instruments. Our findings suggest that the use of a serum-based calibrator provides the most valid comparison between different calcium-ion analyzers and reliably indicates when electrode replacement is needed. PMID- 4017240 TI - Hydroxyurea interferes negatively with triglyceride measurement by a glycerol oxidase method. AB - Measured triglyceride concentrations were extremely low (less than 100 mg/L) in the serum of some patients who were receiving hydroxyurea for myeloproliferative diseases. The assay being used to quantify triglycerides was a "cascaded" enzymatic method involving (a) lipase, to generate glycerol from triglycerides; (b) glycerol oxidase, to convert glycerol to glyceraldehyde, with generation of hydrogen peroxide; and (c) peroxidase, which acts on the hydrogen peroxide with subsequent coupled generation of a red-violet quinone (reagent system used in the Technicon RA-1000). Hydroxyurea added to serum samples appeared to inhibit the action of glycerol oxidase, with a stoichiometric relation to the concentration of substrate (a decrease of roughly 2.4 mmol/L in measured triglyceride per 1 mmol of hydroxyurea per liter). A different enzymatic assay for triglycerides, which involves glycerol kinase (Beckman Instruments) did not show this effect of hydroxyurea. PMID- 4017241 TI - Two radioassays for serum vitamin B12 and folate determination compared in a reference interval study. AB - For 154 subjects, we verified that vitamin B12 and folate status was normal, using as criteria the average polymorphonuclear lobe count, mean corpuscular volume, and hemoglobin concentration. We then used blood from these subjects to compare values obtained with two radioassay kits, each designed for simultaneous vitamin B12 and folate determination. Although regression analysis showed reasonable correlation between the folate (r = 0.87) and vitamin B12 (r = 0.94) kits, we observed significant differences in the overall mean values for vitamin B12 (p less than 0.01) and folate (p less than 0.001) as measured with the kits in this population. Radioassay standard-curve data for the folate assays were similar, but these data indicated greater sensitivity at low concentrations for one vitamin B12 kit than the other. Using reference intervals recommended in the kit inserts, we found that the vitamin B12 status for 9% of these subjects would have been misclassified by one kit, 2% by the other. PMID- 4017242 TI - Three techniques compared for detecting bacteriuria in symptomatic patients. AB - We wanted to determine whether the microscopic evaluation of urinary sediment could be replaced by either a biochemical determination (Chemstrip-9) or a colorimetric staining procedure (Bac-T-Screen), and to evaluate the feasibility of omitting from urinalyses attempts to culture urines. Cultures were considered positive when colony counts were greater than or equal to 10(3) for catheterized patients and greater than or equal to 10(4) for noncatheterized patients. The results of three separate studies on symptomatic patients showed a progressive decline in the sensitivity of the Chemstrip-9, which is a test for leukocyte esterase activity, and a difference in the sensitivity of the Bac-T-Screen between two of the studies. Neither test was consistently more sensitive or more predictive of a positive culture than was urine microscopy. By the end of the third study, we were convinced that the three methods are comparably sensitive and specific. Because 13 to 36% of positive cultures would be missed by these techniques, urine from symptomatic patients should routinely be cultured. PMID- 4017244 TI - Liquid-chromatographic measurement of riboflavin in serum and urine with isoriboflavin as internal standard. AB - We describe how riboflavin can be precisely and accurately measured in serum and urine. A structural analog, isoriboflavin, is used as an internal standard. Urine samples are prepared by adding the internal standard and trichloroacetic acid. For serum, proteins are denatured with trichloroacetic acid. A simple Sep-pak treatment of the supernate removes contaminating interferents. Within- and between-run precision is reflected by respective CVs of 2.2 and 4.9% for urine at 180 micrograms/L and 4.4 and 7.3% for serum at 10 micrograms/L. The standard curve is linear far beyond the concentrations encountered in serum and urine. The detection limit is estimated to be 10 micrograms/L and 1 microgram/L for urine and serum, respectively. The normal reference interval, as determined from 50 results for each matrix, is 36 to 349 micrograms/g of creatinine (mean 112 micrograms/g) for urine and 5.5 to 14.4 micrograms/L (mean 8.8 micrograms/L) for serum. Both distributions are skewed. The method is suited for routine use. PMID- 4017243 TI - Application of a statistical approach to determining reference intervals in clinical chemistry. AB - In clinical chemistry a linear-regression model may be used to determine reference intervals. A crucial point in this approach is the choice of variables to introduce into the model. In the present paper, we have applied a nonautomatic selection procedure, known as "element analysis," to a sample of 126 individuals from a small, ethnically homogeneous community in southern Italy. We investigated the effects of four independent variables--sex, age, weight, and alcohol consumption--on values for serum urea. Only sex and age proved to affect the urea values and were therefore introduced into the final model. This approach may be useful in determining reference intervals from observational studies when it is difficult to control a priori relevant factors. Moreover, variables may be selected not only on the basis of statistical criteria, but also according to biochemical and medical criteria. PMID- 4017245 TI - Three methods compared for determining phosphatidylglycerol in amniotic fluid. AB - Phosphatidylglycerol is one component of amniotic fluid that is unaffected by several of the reported interferences with conventional thin-layer chromatographic measurement of phospholipid. To compare a rapid immunological agglutination test, "Amniostat-FLM", with two-dimensional thin-layer chromatography, we determined phosphatidylglycerol by both methods in 41 amniotic fluid specimens obtained at 31 to 40 weeks of gestation. We also assayed phosphatidylglycerol in 14 of these specimens by an enzymic, colorimetric procedure. The agglutination test is rapid and simple but relatively insensitive; it yielded positive results for only seven of 23 specimens in which phosphatidylglycerol was detected by thin-layer chromatography. In 18 specimens in which no phosphatidylglycerol was detected by thin-layer chromatography, results by Amniostat-FLM were also negative; however, eight of these specimens, assayed by the enzymic method, had phosphatidylglycerol present. Apparently, the Amniostat-FLM detects phosphatidylglycerol only at concentrations exceeding 25 mumol/L, or more than 15% of the total phospholipid composition. PMID- 4017246 TI - Three turbidimetric methods for determining total protein compared. AB - We used human serum protein fractions to evaluate the sensitivity and bias of three turbidimetric methods for determining concentrations of proteins. Each fraction (Cohn Fractions II, III, IV, and V) was assigned a protein concentration value that was determined by the biuret method, which we calibrated with purified monomer of human serum albumin. All three turbidimetric methods (those involving sulfosalicylic acid/sodium sulfate, trichloroacetic acid, and alkaline benzethonium chloride) gave acceptable results for Fraction V with crystallized human serum albumin as the reference material, but there was bias by each of the three methods for the three globulin fractions. The method involving alkaline benzethonium chloride with measurement at 450 nm had the best sensitivity within the range of linearity and the most consistent bias among the three globulin fractions. These results define the dilemma for valid calibration of these methods for total serum protein in cerebrospinal fluid and urine. PMID- 4017247 TI - Glucose transport in erythrocytes of diabetic and healthy children as related to hemoglobin A1c. AB - We studied glucose transport under physiological conditions (38 degrees C, pH 7.2, 5 mmol of glucose per liter) in erythrocytes of nine diabetic children with hemoglobin A1c values ranging from 6.6 to 13.8%, and in erythrocytes from six healthy children. Glucose transport was determined to be 2.38 (SD 0.16) X 10(-10) mol/cm2 X s (n = 18), and 2.47 (SD 0.18) X 10(-10) mol/cm2 X s (n = 12) in erythrocytes from diabetics and controls, respectively. The corresponding values for hemoglobin A1c were 11.0% (SD 2.3%) for the diabetics and 5.6% (SD 0.3%) for the controls. Thus the concentration of hemoglobin A1c, which reflects the degree of glycation of membrane proteins, differs significantly (p less than 0.001) between the two groups, whereas there was no significant variation (p greater than 0.1) in D-glucose transport. We conclude that glycation of the integral membrane protein that mediates glucose transport has no effect on transport function under physiological conditions. PMID- 4017248 TI - Thiocyanate vs cotinine as a marker to identify smokers. PMID- 4017249 TI - Temperature coefficient for erythrocyte sedimentation rate as measured in plastic tubes. PMID- 4017250 TI - Rapid procedure for finger-stick whole-blood analysis for serotonin by electrochemical-array-cell liquid chromatography. PMID- 4017251 TI - Ambient temperature and thyrotropin concentration in serum. PMID- 4017252 TI - Serum bile acids determined with an RA 1000 analyzer. PMID- 4017253 TI - Diethylstilbestrol inhibits the estrogen-binding activity of pregnancy plasma; possible role in DES-associated pathology. PMID- 4017254 TI - Direct radioimmunoassay of melatonin in saliva. PMID- 4017255 TI - Pitfall in treatment of anion-exchange resin before total iron-binding capacity in serum is measured. PMID- 4017256 TI - Use of lithium to determine volume of 24-h urine specimens. PMID- 4017258 TI - More precise determination of the cerebrospinal fluid IgG index. PMID- 4017257 TI - Theophylline concentrations in serum, plasma, and whole blood compared. PMID- 4017259 TI - Commercial kit for total estriol used for monitoring 24-h urinary estriol in non pregnant women. PMID- 4017260 TI - 'Chemical hyperthyroidism': the significance of elevated serum thyroxine levels in L-thyroxine treated individuals. AB - We have previously reported that L-thyroxine treated patients may often have elevated serum T4 concentrations and yet show no clinical signs of hyperthyroidism. We found that such patients had normal serum T3 concentrations. The present study explored the relationship between serum T3 and T4 and dosage of L-thyroxine. Retrospective analysis of 99 patient records was performed. There was an increase of serum T4, serum T3 resin uptake (T3R), and T3 with increasing dose of L-thyroxine. The T3/T4 ratio decreased with increasing dose of L thyroxine and with increasing T4. This phenomenon was analysed prospectively by starting 23 individuals on L-thyroxine and progressively incrementing the dose until either symptoms of hyperthyroidism developed or T4 levels exceeded the upper unit of the normal range. Once again, there was a progressive increase in serum T4, T3R, and T3 with increasing dose of L-thyroxine. At even the lowest dose of L-thyroxine (0.05 mg), there was a marked fall in T3/T4 ratio as compared to untreated individuals. The T3/T4 ratio fell further with increasing dose but with a fairly weak correlation. The decrease in T3/T4 ratio showed a much stronger correlation with serum T4. Of the 23 individuals, all exceeded the upper limit of the normal range of serum T4. No individual with elevated T4 developed clinical signs of hyperthyroidism unless serum T3 was also elevated beyond the normal range. Of eight individuals who reached elevated T3 levels, six demonstrated clinical signs of hyperthyroidism.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4017261 TI - Testosterone replacement in hypogonadal men: effects on obstructive sleep apnoea, respiratory drives, and sleep. AB - The obstructive sleep apnoea syndrome occurs predominantly in men. To determine the effect of testosterone on ventilatory function and whether testosterone may play a role in the development of obstructive apnoea, we performed waking ventilatory drive studies and sleep studies in five hypogonadal men. These androgen-deficient subjects were studied both while receiving no treatment and after six weeks of testosterone replacement therapy (testosterone oenanthate 200 mg i.m. every 2 weeks). Hypoxic ventilatory drive decreased significantly, from 158 +/- 39 (mean +/- SEM) off testosterone to 88 +/- 19 on testosterone therapy (P less than 0.05). Hypercapnoeic ventilatory drive did not change significantly on testosterone. Obstructive sleep apnoea developed in one man and markedly worsened in another man in association with testosterone administration. Both of these subjects also exhibited marked decreases in oxygen saturation with the development of cardiac dysrhythmias during sleep and large increases in haematocrit. The remaining three hypogonadal men did not demonstrate significant sleep apnoea either on or off testosterone. The percentage of sleep time spent in REM sleep increased from 14 +/- 3% to 22 +/- 2% when the men were receiving testosterone (P less than 0.01), but the episodes of sleep apnoea tended to occur during non-REM sleep. We conclude that in some hypogonadal men, replacement dosages of testosterone may affect ventilatory drives and induce or worsen obstructive sleep apnoea. The obstructive sleep apnoea syndrome is a potential complication of testosterone therapy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4017262 TI - Bone metabolism in acute parathyroid crisis. AB - Studies on bone metabolism described in a fatal case of acute parathyroid crisis, occurring in a 48-year-old woman in whom serum immunoreactive parathyroid hormone levels were very high, and a 5 g parathyroid adenoma was found at operation. The histological and biochemical findings suggested a massive and acute increase in bone resorption. There was, however, no evidence of any compensatory increase in bone formation, indicating that acute parathyroid crisis is characterized by a marked dissociation between bone resorption and formation. It is suggested that a sudden fall in oestrogen levels may contribute to the pathogenesis of this disorder. PMID- 4017263 TI - Recent advances on endogenous Na+,K+-ATPase inhibitors: clinical investigation and purification. AB - Evidence exists which demonstrates the relationship between a Natriuretic Factor or Na+,K+-ATPase inhibitor and volemic expansion, both in man and animal. Patients having extracellular volume expansion have been studied for the effect of their plasma on erythrocytes 3H-ouabain binding. High levels of ouabain-like activity was found in plasma from acromegalic patients and patients with chronic renal failure. High levels were also observed in some hypertensive patients. A partial purification of such a compound was performed from urine of hypertensives. The partially purified compound inhibited to a greater extent the Na+,K+-ATPase semi-purified from dog kidney than that from sheep brain. The present data are consistent with the possible regulation of the activity or the secretion of plasma ouabain-like activity by extracellular volume. PMID- 4017264 TI - The importance of endogenous digoxin-like factors in rats with various forms of experimental hypertension. AB - The acute administration of anti-digoxin serum (ADS) caused a pronounced long lasting blood pressure decrease in young DOCA-salt hypertensive rats. The decrease of blood pressure was only moderate in 1K-1C Goldblatt rats while there was no change of blood pressure after the ADS injection in spontaneously hypertensive rats. However, the blockade of endogenous digoxin-like factors lowered blood pressure only in those hypertensive rats which were treated with DOCA-saline from youth but not in animals treated in the same manner only in adulthood. The age period at which salt intake was increased, could be responsible for the susceptibility of animals to salt- and volume-dependent forms of experimental hypertension as well as for the participation of slow acting humoral pressor agents in the induction and/or maintenance of elevated blood pressure. It is evident that endogenous digoxin-like factor(s) participate in a greater response of young rats to the hypertensive stimuli. PMID- 4017265 TI - Arguments for the presence of a Na-K ATPase pump inhibitor in the plasma of uremic and essential hypertensive patients. AB - The effect of salt and/or volume depletion has been tested in 6 end-stage renal disease and 11 essential hypertensive patients (HTA) on red blood cell (RBC) ionic fluxes. Volume depletion promotes an increase in the RBC Na-K ATPase activity with, as a result, a significant decrease in intracellular sodium concentration [Na)ic). Moreover, a factor has been found in the plasma of uremic subjects which causes natriuresis when injected in rat renal arteries. The concentration of this factor decreases during dialysis in relation to the weight loss and the increase in the RBC Na-K pump activity. In essential hypertension, the effect of a low salt diet on the blood pressure is correlated with the improvement of RBC Na-K ATPase activity. These experiments illustrate the presence of a Na-K ATPase inhibitor in the plasma of these subjects, dependent on sodium and water balance. PMID- 4017266 TI - Studies on the role of intracellular sodium and calcium in the centrally mediated pressor effects of CSF [Na+], ouabain and angiotensin II in anesthetized dogs. AB - Cerebroventricular infusions of hyperosmotic Na+ solutions, ouabain and/or Angiotensin-II produced significant increases in the arterial blood pressure in chloralose anesthetized, vagotomized dogs. A lower concentration of ouabain (10( 6) M) which did not alter blood pressure, significantly potentiated the centrally mediated pressor effects of hyperosmotic Na+ and angiotensin-II. Hence, the data suggested that the magnitude of the central pressor effects of Angiotensin-II or hyperosmotic Na+ may depend upon net accumulation of sodium in the neuronal cells. Prior cerebroventricular infusions of felodipine, a "calcium antagonist," significantly inhibited the pressor actions of higher concentrations of ouabain as well as that of hyperosmotic Na+-solutions, indicating that cellular calcium may be essential for triggering these central effects. These studies collectively indicate that disturbances in the Na+-transport in the neuronal cells may account for the involvement of the central nervous system in various types of hypertension. PMID- 4017267 TI - Observations on the "cascade" of Na-K-ATPase inhibitory and digoxin-like immunoreactive material in human urine: possible relevance to essential hypertension. AB - Previous investigations have demonstrated an increased amount of a sodium pump inhibitor (N.H.) in plasma from humans with essential hypertension and from animals with various forms of experimental hypertension. The present study has employed Sephadex column and C18 reverse phase separation of urines from patients with essential hypertension and normal controls to distinguish "high", "intermediate" and "low" molecular weight forms of N.H., measured through properties of Na-K-ATPase inhibition and digoxin-like immunoreactivity. The major difference between hypertensive and normotensive urines was a highly significant increase in the "intermediate" molecular weight form of N.H., as measured by Na-K ATPase inhibition. In contrast, digoxin-like immunoreactivity was significantly decreased in urine from hypertensive patients. The results are compatible with an hypothesis that the defect in some forms of essential hypertension may be partial inhibition of enzymatic conversion of intermediate to final form of N.H., with the increased sodium pump inhibition primarily related to the precursor. PMID- 4017269 TI - Symposium on osteosynthesis in foot and ankle surgery. PMID- 4017268 TI - Investigations of endocrine disorders. PMID- 4017271 TI - Digital arthrodesis. AB - This article briefly reviews the literature regarding digital arthrodesis. It presents an in-depth description of the techniques presently used for such procedures at the California College of Podiatric Medicine. PMID- 4017270 TI - External fixation. Its use in podiatric surgery. AB - Rigid fixation of osseous fragments with the ability to supply additional compression or distraction at will is achieved only by external fixation. Of course, the treatment of nonunions, infections, fixation of osteotomies, fusion of joints, and lengthening of bone can be accomplished by other satisfactory means with and without fixation. External fixation is only one method of fixation. From this list the practitioner can choose the method of fixation best suited to the contemplated procedure and the one with which the surgeon feels most comfortable. However, a good surgeon will have prepared alternative methods of fixation if, in fact, the first and preferable method of fixation fails. It would be wonderful if our plans became a reality; quite often they do not and this is what one must prepare for. External fixation in many of the cases presented was not the original form of fixation to be used; in a few cases it had not been seriously considered. Fortunately, however, it was considered and allowed a difficult situation to be remedied with relative ease. Although elaboration of the categories in which external fixation was employed has been brief, the numerous presentations lend themselves to further investigation into external fixation. PMID- 4017272 TI - The hazards of internal fixation in podiatry. AB - There are several ways to avoid the iatrogenic complications or hazards of internal fixation. The surgical approach should be planned well in advance. The instruments and materials to be used intraoperatively should be checked before beginning the operation to assure that there are adequate materials of appropriate length and thickness. Also, all materials should be checked for major defects (see Fig. 11A). Good tissue dissection and atraumatic surgical technique is essential to limit excessive tissue destruction. Reduction of the fracture fragments should be obtained prior to fixation. While applying fixation devices, the fragments should be held stable. Intraoperative radiographs are necessary to demonstrate appropriate positioning of the internal fixation device and the proper alignment of the fracture fragments. If the alignment is not satisfactory, repositioning of the devices can and should be made. Preoperative practice and familiarity with the fixation devices is an essential part of shortening the operative time and helping to assure optimum fixation stability. A poor time to learn the techniques for internal fixation is during surgery. Good postoperative care is essential to optimize fracture fragment healing results. PMID- 4017273 TI - Co-cultivation studies in the expression of fragile (X) (q27) in lymphocytes. AB - Co-cultivation studies in different combinations have been carried out between cells which have been found to be positive for the fragile (X) (q27) and control cells. As no increase or decrease was discernible in the level of Fra(X) detected in 'positive' cells, and no fragility was introduced into the 'negative' cells, it was concluded that there had been no intercellular co-operation, and a diffusible expression or suppression factor was not involved. PMID- 4017274 TI - Autoimmune polyendocrinopathy--candidosis--ectodermal dystrophy (APECED): autosomal recessive inheritance. AB - A genetic analysis was made of 58 patients and their 42 families with APECED (autoimmune polyendocrinopathy--candidosis--ectodermal dystrophy). APECED is characterized by hypoparathyroidism, primary adrenocortical failure and chronic mucocutaneous candidosis, but none of its components is constant. Other endocrine deficiencies can occur as well and also dystrophy of dental enamel and nails. The proportion of affected siblings was 0.147 +/- 0.034 (S.D.) when corrected for truncate single ascertainment, 0.246 +/- 0.019 when corrected for a priori truncate complete ascertainment and 0.240 +/- 0.047 when corrected for a posteriori truncate complete ascertainment. The male/female ratio was 1.04. The results are compatible with autosomal recessive transmission. No heterozygous manifestations of the gene were found. The gene is enriched in isolated subpopulations in central and eastern Finland. APECED is part of the "Finnish heritage of disease". PMID- 4017276 TI - Deficiency of fumarylacetoacetase without hereditary tyrosinemia. AB - A variant of the enzyme fumarylacetoacetase (FAH) (E.C.3.7.1.2) in healthy individuals, determined by the enzyme activity, is reported. Analysis of family members of probands with low FAH activity suggests that the enzyme variant causing low activity could be the product of a pseudodeficiency gene. Assumed homozygotes for this gene have only slightly higher enzyme activity than patients with the metabolic disorder hereditary tyrosinemia I (hepatorenal type). No clinical abnormalities have been found in association with the postulated gene. PMID- 4017275 TI - Maximal low density lipoprotein receptor activity and the effect of lipid lowering diet on total serum cholesterol. AB - This study was undertaken to test if the effect of lipid lowering diet on total serum cholesterol, is influenced by maximal low density lipoprotein (LDL) receptor activity. LDL receptor activity was determined in cultured skin fibroblasts from hypercholesterolemic, male subjects after lipid lowering diet intervention. The LDL receptor values from 15 subjects (responders) who had responded well to a lipid lowering diet and from 14 subjects (non-responders) who had responded poorly, were compared. The responders had a reduction in total serum cholesterol of 29.4%, and the non-responders had a reduction of 8.2% (p less than 0.0001). The higher values for LDL receptor activity among the responders did not reach statistical significance. For all 29 subjects there were non-significant positive correlations between reductions in total serum cholesterol and values for association or degradation of 125I-LDL at 37 degrees C (r = 0.16, p = 0.40 and r = 0.17, p = 0.38, respectively). Thus, it seems that maximal LDL receptor activity is not a major predictor for the response of lipid lowering diet on total serum cholesterol levels in hypercholesterolemic subjects without autosomal dominant familial hypercholesterolemia. PMID- 4017277 TI - Familial recurrence of terminal transverse defects of the arm. AB - Three families in which relatives were concordant for upper limb terminal transverse defects are described. These families and previously reported ones with similar recurrence of terminal transverse defects are reviewed and analyzed. It is suggested that, at least in part, the patterns of relatedness for these recurrences more likely are the result of a genetic contribution to the development of this birth defect, rather than such recurrences being solely due to chance. PMID- 4017278 TI - Congenital contractural arachnodactyly. Report of four additional families and review of literature. AB - We report here four families with congenital contractural arachnodactyly (CCA) in which a wide range of phenotypic expression is observed. In one family with a large number of affected individuals the condition is mildly expressed. These individuals usually have crumpled ears, camptodactyly with ulnar deviation of the fingers, adducted thumbs, limited elbow and/or knee extension, and hypoplasia of the calf muscles. Arachnodactyly is not a constant feature. No spinal deformities are present and only the proband has clubfoot deformities. With time, affecteds have experienced spontaneous improvement of their contractures and their condition in adulthood has not interfered with a normal lifestyle. Within this family there is little phenotypic variation between affected individuals. Those affected within each of the other families have had varying degrees of severity of the condition. A review of 29 other kindreds described in the literature with congenital contractural arachnodactyly shows that in this condition the most common features are abnormally formed ears, camptodactyly, arachnodactyly, adducted thumbs, limited movement of the elbows and knees, and underdevelopment of the calf muscles. Spontaneous improvement of the contractures with age is reported in 94% of cases. Kyphosis, scoliosis or kyphoscoliosis occurred in 50% and these defects were present in those who where more severely affected with CCA. No ocular problems have been reported in this syndrome, but congenital heart defects have occurred in 14.7%. Marfan syndrome is the most important condition to differentiate from congenital contractural arachnodactyly since these two conditions are similar phenotypically. However, in the former there are frequently serious ocular and cardiovascular problems which lead to significant morbidity and/or early death. PMID- 4017279 TI - The FG syndrome: 7 new cases. AB - The X-linked FG syndrome is characterised by mental retardation, congenital hypotonia and constipation (which may both be severe), structural anal anomalies and relative macrocephaly in some, and an unusual and characteristic facial appearance. We describe 7 males from 4 families. One had anal stenosis. Two of the mothers and one sister show probable carrier manifestations. The features of the FG syndrome are individually non-specific. We emphasize that the characteristic combination of features is needed to avoid overdiagnosis. PMID- 4017280 TI - Familial syndrome with some features of the Langer-Giedion syndrome, and paracentric inversion of chromosome 8, inv 8 (q11.23----q21.1). AB - A family is reported with an autosomal dominant inherited syndrome presenting some of the typical features of the tricho-rhino-phalangeal syndrome type II (TRP II) or Langer-Giedion syndrome. The critical region for the expression of the syndrome seems to be at band 8q24.1. In the affected members of the family reported here, anomaly of chromosome 8 was noted, involving however the proximal part of the 8 long arm, which was interpreted as a paracentric inversion. Whether the anomaly is causally or only casually related to the syndrome is a matter of discussion. PMID- 4017281 TI - Multiple dysmorphic features and pancytopenia: a new syndrome? AB - Various degrees of bone marrow aplasia have been described in association with distinctive congenital anomalies such as the Fanconi Pancytopenia Syndrome (F.P.S.), Thrombocytopenia Absent Radii Syndrome (T.A.R. Syndrome) the Aase Syndrome and Diamond-Blackfan Anemia. This case report describes a child with pancytopenia and several dysmorphic features which have never collectively been described in any of the bone marrow aplasia syndromes listed above. In this paper, we report a constellation of dysmorphic features and pancytopenia which may constitute a new syndrome. PMID- 4017282 TI - Dominantly inherited syndrome of microcephaly and congenital lymphedema. AB - A Chinese family is reported in which microcephaly and congenital lymphedema have been observed in at least 4 generations. This combination of symptoms can be presumed to represent a rare but well defined hereditary syndrome transmitted by an autosomal dominant gene. PMID- 4017283 TI - Fetal mortality in oral cleft families (X): a response. PMID- 4017284 TI - Werdnig-Hoffmann disease on Reunion Island: a founder effect? PMID- 4017285 TI - The splenic extraction ratio of antibody-coated erythrocytes and its response to plasma exchange and pulse methylprednisolone. AB - Splenic blood flow was measured in a series of normal subjects and patients with connective tissue diseases by measuring the rate of equilibration and the partition of 111In-labelled autologous platelets between blood and spleen. These data were used to quantify the role of splenic blood flow in determining the splenic clearance of IgG coated erythrocytes (IgG-RBC) from the circulation. Previous studies have interpreted the clearance rates of IgG-RBC only in terms of splenic reticuloendothelial function. Splenic blood flow was increased in seven of eight patients with systemic lupus erythematosus (SLE), six of 10 patients with rheumatoid arthritis (RA) and in all five patients with essential mixed cryoglobulinaemia (EMC) compared with a series of thirteen normal subjects. Expressing the rate constant of clearance of IgG-RBC as a fraction of splenic blood flow gave a value for the 'extraction ratio' of IgG-RBC (a specific measurement of reticuloendothelial function, corrected for splenic blood flow). Normal splenic extraction ratio of IgG-RBC was calculated to be 32%. All the patients with SLE and with EMC had reduced extraction ratios (in seven out of 13 patients less than 10%). In RA the extraction ratio tended to be normal (average 27.3%) but variable (9-59%). Following plasma exchange in nine patients, a significant increase in IgG-RBC extraction ratio (average of 39% with respect to pre-exchange values, P less than 0.05) was found. In contrast there was no significant change in extraction ratio following pulse methylprednisolone therapy in a further nine patients. Although the rate constant of clearance of IgG-RBC decreased by an average of 33% (P less than 0.01) in the latter group, it was matched by an equal decrease of splenic blood flow (average 37%, P less than 0.01) and so extraction ratio showed no change. These data indicate that quantification of splenic reticuloendothelial function requires measurement of both IgG-RBC clearance and of splenic blood flow. PMID- 4017286 TI - Depressed classical complement pathway activities in chronic lymphocytic leukaemia. AB - Haemolytic activities of the classical and alternative complement pathways, and levels of C1, C4, C3, factor B and C1 inhibitor (C1-INH) were measured in 85 serum samples from 46 patients with chronic lymphocytic leukaemia (CLL). Significantly decreased mean C1 and C4 levels were found, and the haemolytic activities of these components were low or low normal in more than 50% of the sera tested. In 15 sera from 5 patients a complement profile characteristic of acquired C1-IHN deficiency was observed. These results indicate that the depression of the activity of the classical complement pathway is a frequently occurring feature in CLL. PMID- 4017287 TI - Purification of the Sm nuclear autoantigen. Detection and clinical significance of IgM antibody. AB - Sm antigen from rabbit thymus acetone powder was purified using a combination of ammonium sulphate precipitation, DEAE-Sephacel and hydroxyapatite chromatography. This preparation was devoid of previously identified nuclear antigens including ribonucleoprotein (U1-RNP), proliferating cell nuclear antigen (PCNA), Sjogren's syndrome antigen A (SS-A/Ro), Sjogren's syndrome antigen B (SS-B/La), Sjogren's lupus antigen (SL), scleroderma antigen 70 (Scl-70), DNA and histones. The purified material was used in an enzyme linked immunosorbent assay (ELISA) to detect anti-Sm antibody. All sera with precipitating Sm antibody detected by immunodiffusion gave reactions in ELISA greater than 0.40 OD405 and contained predominantly IgG anti-Sm antibody. Of 112 sera which did not have anti-Sm by immunodiffusion there were five which gave reactions greater than 0.40 OD405. Four of these five sera contained only IgM antibody and the fifth contained both IgM and IgG. Of these five, one came from a 'normal' control who had a positive anti-nuclear antibody (ANA), facial rash and diabetes, two were from patients with systemic lupus erythematosus (SLE) and two were from patients with mixed connective tissue disease (MCTD). These findings demonstrate that there are patients whose anti-Sm response may be restricted to IgM and in some of these patients the clinical presentation may be different from that of classical SLE. PMID- 4017288 TI - The role of C1, C1-inactivator and C4 in modulating immune precipitation. AB - To clarify the mechanism of inhibition of immune precipitation by early components of the classical pathway of complement, aggregation of 125I-BSA-rabbit anti-BSA antibody complexes was performed in the presence of purified C1, C1 inactivator (C1-In) and C4. C1 delayed the rate of immune precipitation in a concentration dependent manner. This phenomenon was not influenced by the presence of 0.3 mM p-nitrophenyl-p-guanidinobenzoate (NPGB) which inhibits C1 activation. The antiaggregational effect of C1 was reversed by 10 mM EDTA and by C1-In at a C1-In/C1 molar ratio of greater than or equal to 4/1. C1-In was not effective when the reaction was performed in the presence of NPGB. Thus, although the inhibitory effect of C1 on immune precipitation was not dependent upon C1 activation, the formation of C1 was required to observe the effect of C1-In. The addition of C4 to C1 did not modify the slow aggregation of complexes, even when a limiting concentration of C1 was used. C1-In and EDTA were both able to cause similar rapid precipitation of complexes prepared in the presence of C1 and C4, demonstrating that C4 did not play a significant role in delaying the precipitation reaction. However, soluble complexes prepared in the presence of C1 and C4 were specifically precipitated by the addition of excess anti-C4 antibody, attesting to the binding of C4 to immune complexes. These observations suggest that the processing of immune complexes in vivo may not be similar in different classical pathway complement deficiency states. PMID- 4017289 TI - Anti-acetylcholine receptor idiotypes in myasthenia gravis analysed by rabbit anti-sera. AB - Anti-idiotype sera, raised in rabbits against anti-acetylcholine receptor (AChR) (idiotype) purified from the serum of three myasthenia gravis patients, inhibited binding of homologous idiotype to the AChR by up to 80%. The expression of idiotype in the three individuals changed very little over a period of several years, during which they showed a declining trend in overall anti-AChR antibody. Only one of the four anti-idiotype sera inhibited the binding of anti-AChR from a number of other patients. Our results indicate a consistency of idiotype expression within an individual, and fail to show substantial idiotype sharing between individuals. PMID- 4017290 TI - Immune deposits in normal skin of patients with systemic lupus erythematosus: relationship to the serum capacity to solubilize immune complexes. AB - Immunofluorescent deposits at the dermal-epidermal junction (DEJ) of the skin (lupus band test or LBT) were evaluated in 134 patients with various connective tissue diseases. LBT was found positive in 23 of 32 (71.8%) patients with systemic lupus erythematosus (SLE), in 3 of 53 (5.6%) patients with rheumatoid arthritis (RA), and in 1 of 5 cases of mixed connective tissue disease (MCTD). No deposits were found in patients with systemic sclerosis and with vasculitis. In patients with SLE a positive LBT showed a direct correlation with serum Clq binding activity (ClqBA) and with hypocomplementemia. The mean ClqBA was 13.49 +/ 12.85 and 2.38 +/- 2.27% in SLE patients with positive and negative band test, respectively (P less than 0.005). Likewise depressed mean serum levels of C3 and C4 were detected in patients with skin deposits (P less than 0.005). Sera from SLE patients showed an overall decreased capacity to solubilize preformed immune complexes when compared to normal sera. Furthermore 10 band-positive patients were less able to solubilize immune complexes than sera from LBT-negative lupus patients (45 +/- 16 and 62 +/- 11%, respectively; P less than 0.01). Also the capacity to inhibit the precipitation of immune complexes was decreased in SLE patients with negative LBT (P less than 0.05). In conclusion our data suggest that in SLE patients a decreased complement-mediated solubilization of immune complexes is involved in the persistence of high levels of circulating immune aggregates and, considered its correlation with positive LBT, may be responsible for the deposits of immunoglobulins at the dermal-epidermal junction of the skin. PMID- 4017291 TI - Binding, endocytosis, and degradation of model immune complexes by murine macrophages at various levels of activation. AB - To determine if stimulation of macrophages enhances their capacity to recognize and process immune complexes, the binding, endocytosis, and degradation of soluble model immune complexes in murine macrophages have been measured. These complexes are composed of covalently crosslinked dimers and heavy oligomers of murine IgG antidinitrophenyl antibodies. Resident (unstimulated), inflammatory (thioglycolate-elicited), and activated (bacillus Calmette-Guerin-elicited) macrophages were studied. Cells elicited with either agent bound five times more dimers or heavy oligomers than did resident cells. Stimulated macrophages internalized and then degraded 50-60% of those heavy oligomers initially bound to the surface of the cell. Resident macrophages, however, were about 70% as efficient as stimulated cells at degrading intracellular complexes. Although dimers avidly bound to all three types of macrophages, they were internalized poorly and were degraded minimally. Intracellular complexes were degraded within lysosomes as determined by centrifugation of cell homogenates on Percoll gradients. Following endocytosis of heavy oligomers, Fc receptors on each type of macrophage were down-modulated to 30% of control levels. PMID- 4017292 TI - Selective IgA deficiency in the dog. AB - This study documents the occurrence of selective IgA deficiency in the dog. This is a unique spontaneous animal model with clinical and immunologic findings similar to that of selective IgA deficiency in humans, the most common human primary immunodeficiency. The disease in the dog is characterized by chronic, recurrent respiratory infections and dermatitis, low concentrations of serum IgA, normal concentrations of serum IgG and IgM, normal T-cell function as measured by lymphocyte transformation tests, the presence of autoantibodies, and a defect in the maturation or terminal differentiation of IgA B cells into IgA-secreting plasma cells. PMID- 4017293 TI - Immune responsiveness of monkeys exposed chronically to cigarette smoke. AB - Eleven adult male stumptailed monkeys (Macaca arctoides) were chronically exposed to either a low dose (human equivalent of 1 pack/day) or a high dose (human equivalent of 3 packs/day) of high-tar, high-nicotine University of Kentucky reference cigarette smoke for 4-8 years. Several parameters of their immunological response were compared to six nonsmoked control animals. The results from these experiments suggest that cigarette smoking does not significantly affect the response of spleen cells to the mitogens phytohemagglutinin or lipopolysaccharide. However, spleen cells from animals subjected to the heavy dose of cigarette smoke demonstrated a significant reduction in their natural killer cell-mediated lytic activity and a decreased response to concanavalin A. These results suggest that cigarette smoking may have a differential effect on lymphocyte subpopulations, and that the effects on the immune response are related to the dose of cigarette smoke. PMID- 4017294 TI - Lymphokines induce changes in morphology and enhance motility of endothelial cells. AB - The influence of lymphokines, the soluble mediators produced by lymphocytes, on the morphology and the motility of endothelial cells in vitro is described. Lymphokines induced an altered morphology and an increased motility of canine and human venous endothelial cells. The action of the lymphokines was species specific. The data are discussed in relation to in vitro and in vivo data on the behavior of endothelial cells in inflammation. The in vitro experiments allow further study of the role of endothelial cells in inflammatory and immunological processes. PMID- 4017295 TI - A low molecular heparin fraction as an anticoagulant during hemodialysis. AB - During 18 hemodialyses of patients with chronic uremia a low molecular weight heparin fraction (mean MW 5000 d) was used as an anticoagulant without complications. For comparison conventional heparin was used during 18 dialyses in the same patients. Equipotent doses, with regard to Xa inhibition of heparin and the 5000d fraction, suppressed FPA generation (fibrin formation) equally. The APT times were less prolonged by the 5000d fraction. When the 5000d fraction was doubled in relation to conventional heparin with regard to Xa inhibition, the suppression of FPA generation was more effective than with conventional heparin, without more pronounced APTT prolongations. In conclusion this heparin fraction was found to be useful as an anticoagulant during hemodialysis and to give less pronounced APTT prolongation than conventional heparin. PMID- 4017296 TI - Effect of an optimum dialysis fluid calcium concentration on calcium mass transfer during maintenance hemodialysis. AB - The effect of an optimum dialysis fluid calcium concentration (1.625 mmol/l) on calcium mass transfer from dialysis fluid to patient was assessed in patients on routine hemodialysis. While there was a mean body gain of only 3.0 mmol of calcium during dialysis, a marked variation occurred with losses and gains of body calcium up to 16.4 and 18 mmol respectively. A significant correlation was noted between the mass transfer of calcium and the dialysis fluid calcium concentration (r = 0.834, p less than 0.01) which was found to vary by at least 5%. This variation was due to a manufacturing variation and not due to inaccurate dilution of the dialysis fluid concentrate. These data suggests that such a manufacturing variation may expose maintenance hemodialysis patients to periods of excessive calcium loss or gain and thereby favor renal osteodystrophy or soft tissue calcification. In keeping with published data, the mean measured dialysis fluid calcium concentration (1.61 +/- 0.02 mmol/l) should be satisfactory for most patients and it is recommended that dialysis fluid concentrates be manufactured with closer tolerance limits. PMID- 4017297 TI - Occlusion of the subclavian vein: a complication of indwelling subclavian venous catheters for hemodialysis. AB - We are reporting two cases of subclavian vein occlusion following the use of dual lumen subclavian vein catheters as a temporary access to the circulation for hemodialysis. Both patients presented with arm swelling and developed significant collateral circulation established by venography. There was no recanalization of the veins following removal of the subclavian catheters in both cases. This complication has not been previously reported. Its possible pathogenesis is discussed. PMID- 4017298 TI - Acute renal failure and transient, massive proteinuria in a case of pheochromocytoma. AB - Severe renal impairment and massive proteinuria are rare in pheochromocytoma. We report the case of a patient with pheochromocytoma who repeatedly developed episodes of acute renal deterioration and transient, massive proteinuria. Each episodes followed hypotensive periods, two of which seemed to be induced by administration of metoclopramide. The pathogenetic mechanisms of acute renal deterioration and proteinuria are discussed. PMID- 4017299 TI - First exchange neutrophilia: an index of peritonitis during chronic intermittent peritoneal dialysis. AB - During intermittent peritoneal dialysis (IPD) early diagnosis of peritonitis may be difficult, because of paucity in clinical signs and delays in bacteriologic studies. We examined prospectively leucocyte counts and their differential composition in initial ascites and dialysis effluent of patients on IPD and correlated these findings to the presence of subsequently bacteriologically proven clinical peritonitis. Total leucocyte counts from either ascites or first exchange effluent did not differentiate infected from noninfected patients. In contrast, first exchange effluent neutrophilia (greater than 43%) proved to be an early indicator of infection, being 100% sensitive and 94% specific for peritonitis. We conclude that in such patients peritoneal effluent neutrophilia should be considered an indication of possible infection. PMID- 4017300 TI - Seasonal variations in the incidence of kidney stones in Calgary, Alberta, Canada. PMID- 4017301 TI - Impaired cellular immune responses in adult lipoid nephrosis patients. PMID- 4017302 TI - Noninvasive index of cardiac contractility during stress testing: a collaborative study. AB - The present study was conducted in parallel in three different institutions with a similar purpose but using different technical setups. Based on the experimental demonstration that the external phonocardiogram is similar to the rate of acceleration (d3P/d3t) of the left ventricular pressure, and that catecholamines in a similar way increase the early positive wave of the left ventricular pressure and the first heart sound (S1) of the external phonocardiogram; knowing that exercise causes secretion of catecholamines and sympathetic reflexes, we have studied the S1 changes as a result of exertion in 34 normal young subjects. Blood pressure, heart rate, electrocardiograph, and phonocardiograph recordings of each subject were taken. In 10 subjects, cardiac output was also recorded by impedance cardiography. The result of the study was that the first heart sound increased routinely 4-5 times the normal amplitude; in a few subjects the increase was up to 15 times greater. While the extent of increase of S1 was proportional to the severity and duration of the effort and was usually proportional to the increase of other parameters, exceptions were noted as having marked increase of S1 with moderate increase of either blood pressure or heart rate. This was explained by the different receptors activated by the catecholamines and by the complexity of hormonal and neural influences acting on various organs in a stress test. The amplitude of S1 was found to be a reasonably reliable index for following changes of cardiac contractility during exercise, and the suggestion was made that this parameter should be studied in parallel with the others in routine stress tests. PMID- 4017303 TI - Value of exercise electrocardiography to predict additional jeopardized myocardial regions remote from site of previous myocardial infarction. AB - In order to evaluate the efficacy of exercise electrocardiography (ECG) to identify jeopardized myocardial regions remote from the site of previous infarction, exercise ECG, left ventriculography, and coronary arteriography were performed in 90 patients with previous transmural myocardial infarction (MI). Of the 90 patients, angiographic studies revealed jeopardized myocardial regions in 47 patients. Exercise ECG correctly identified 32 of these 47 patients for a sensitivity value of 68%. There were 43 patients without any additional jeopardized myocardial regions. Exercise ECG correctly identified only 24 of these 43 patients for a specificity value of 56%. The sensitivity and specificity values were similar in patients with prior anterior and inferior wall MI. It is concluded that relatively low sensitivity and specificity values preclude the ability of exercise ECG to accurately identify patients with jeopardized myocardial regions distant from the site of previous MI. Moreover, when such patients were correctly detected, exercise ECG was rather poor in localizing these additional jeopardized myocardial areas. PMID- 4017304 TI - Mechanism underlying the absence of ischemic changes on the exercise electrocardiogram in patients with abnormal exercise thallium-201 imaging and coronary artery disease. AB - Patients with coronary artery disease may have reversible abnormalities on a thallium myocardial perfusion study without simultaneous ischemic changes on the exercise electrocardiogram, but the mechanisms responsible for this disparity have not been fully elucidated. A group of 37 patients with angiographically demonstrated coronary artery disease and abnormal thallium perfusion imaging were divided into two groups on the basis of their exercise electrocardiographic ST segment response. Thirteen patients (Group A) had no significant electrocardiographic changes with exercise, while 24 patients (Group B) had ST changes consistent with ischemia during the test. There were no significant differences in clinical or angiographic characteristics between the two groups. Stress test results showed a similar mean duration of exercise in the two groups (6.2 +/- 1.8 versus 6.7 +/- 2.5 min, p = NS), but the patients in Group A achieved a significantly lower mean maximal heart rate (117 +/- 26 versus 132 +/- 21 beats/min, p less than 0.05) and mean maximal double product (19,650 +/- 5116 versus 22,650 +/- 4871, p less than 0.05). There was no consistent pattern of thallium perfusion abnormality noted in Group A to suggest that a particular region of electrically silent myocardium was responsible for ischemia in the absence of electrocardiographic changes. These results suggest that exercise thallium-electrocardiogram discordance is mediated by the level of myocardial workload achieved. An abnormal perfusion scan accompanying an exercise electrocardiogram which does not demonstrate any ischemic ST change may occur when there is sufficient increase in myocardial oxygen demand to result in differential augmentation of myocardial blood flow, but insufficient imbalance of supply and demand to result in signs of ischemia on the surface electrocardiogram. PMID- 4017305 TI - 24-hour blood pressure recording in patients with orthostatic hypotension. AB - Continuous intra-arterial blood pressure measurement and electrocardiograms were obtained in two ambulatory patients with orthostatic hypotension due to autonomic dysfunction. Systolic and diastolic arterial pressure presented marked variations which took place mainly during the day and were related to several physical activities; however, marked falls in blood pressure were also observed during sleep and at the moment of arousal. A peak incidence of hypotensive events was found in the afternoon, mainly in the hours following the afternoon meal. Recording was repeated after 3 weeks of treatment with propranolol, 40 mg t.i.d. In patient 1, beta blockade drastically reduced the number and severity of hypotensive episodes, while propranolol failed to control blood pressure in patient 2, who experienced a higher number of hypotensive events during treatment. Findings of this study may be relevant to the management of patients with orthostatic hypotension and should contribute to a more accurate characterization of blood pressure profile in autonomic dysfunction. PMID- 4017306 TI - Gout in females: an analysis of 92 patients. AB - Ninety-two females with gout are reported. The preliminary ARA criteria for acute gout classified 60% of the patients. Forty patients were diagnosed by finding tophi or urate crystals in the synovial fluid, 16 patients had the ARA clinical criteria for gout, and a further 36 patients were considered to have good clinical grounds for gouty arthritis. Classification of the patients was difficult. A subacute pauci-/polyarthritis was the presenting feature in 64 (70%) patients and in 49 (77%) there was no history of a preceding recurrent monoarthritis. Seventy-two patients (78%) were on diuretics. Tophi were usually indolent and showed little surrounding inflammation. 87% of the patients had an associated disease. PMID- 4017308 TI - Superoxide dismutases in polymorphonuclear leukocytes from patients with ankylosing spondylitis or rheumatoid arthritis. AB - The activity of cyanide-sensitive and cyanide-insensitive superoxide dismutase (CNs- and CNi-SOD) was measured in polymorphonuclear neutrophils isolated from the blood of patients with ankylosing spondylitis (A.S.) or adults with rheumatoid arthritis (R.A.). Our purpose was to detect alterations in the protecting activity of these enzymes that might cause rheumatic lesions secondary to superoxide anion generation in the inflammatory loci. There was no difference in total SOD activity (CNs + CNi) in either A.S. or R.A. when compared to the control group. In contrast, CNi-SOD activity decreased in R.A. and A.S. and CNs SOD activity rose significantly in A.S. only. None of the changes observed in SOD activity correlated with patient's age, erythrocyte sedimentation rate, clinical evolution of the disease or the drug doses administered. It is concluded that the reduced activity of CNi-SOD might be partly responsible for the reduced protection of the joints against oxygen-free radicals in patients with A.S. or R.A. Other factors however appear to have greater effects on the clinical evolution of these diseases. PMID- 4017307 TI - An animal model to study serum immunoglobulin response to infection by Yersinia enterocolitica. AB - Using an Elisa method, we tested whether the serum immunoglobulin response of CBA/H mice, orally infected by a serotype 03 strain of Yersinia enterocolitica was of sufficient magnitude to serve as an experimental model. We found that the dose of bacteria administered was important. At a dose of 10(10)-10(12) bacteria per mouse, easily detectable IgM, IgG and IgA antibody titers could be obtained. At 10(8) bacteria per mouse, although diarrhea occurred and Yersinia was shed into the stool, the antibody titers were minimal. PMID- 4017309 TI - Plasmapheresis vs total lymphoid irradiation in the treatment of severe rheumatoid arthritis. AB - In an ongoing study patients with severe rheumatoid arthritis (RA) who had previously failed conventional therapy including gold salts and penicillamine were randomly assigned on an open basis to a plasma exchange or fractionated total lymphoid irradiation protocol. Nine patients (eight female, one male) with erosive RA of long duration exchanged 40 ml/kg of plasma over a period of two to four weeks. Nine patients (eight female, one male) with similar characteristics, received 2,000 rads to lymphoid tissues in fractionated doses (200 rads each) over 4 to 5 weeks. Treatment was completed in all patients and follow-up ranged from two to twelve months for plasma exchange and eight to sixteen months for radiation. Results of the study showed subjective and objective improvement including morning stiffness, joint score, and pertinent laboratory evaluation in six patients admitted to plasmapheresis with duration of remission lasting as long as seven weeks. Three patients failed to show any improvement in the activity of the disease. Eight patients on the radiation protocol showed a marked decrease in disease activity which has been maintained until the present time. Side effects for the plasma exchange group included mild febrile reactions during the exchange and one non-A non-B Hepatitis. In the radiation group occipital alopecia, loss of appetite and nausea was seen in all patients and severe leucopenia in one (WBC 500/mm3). The present results suggest that both procedures can reduce disease activity in severe RA. Plasma exchange efficacy appears to be short-lived when compared to total lymphoid radiation. The latter was poorly tolerated by all patients submitted to the program. PMID- 4017310 TI - Antibodies to cardiac conducting tissue in progressive systemic sclerosis. AB - Cardiac conducting tissue antibodies (CCTA) were detected, using indirect immunofluorescence, in 8 (25%) out of 32 sera from patients with progressive systemic sclerosis (PSS) and in 39 (35%) out of 110 with rheumatoid arthritis (RA). Conduction abnormalities, namely right bundle branch block, were present in 19 (59%) of the PSS patients and in 37 (32%) of the RA cases. No significant correlation was found between the prevalence of CCTA and conduction abnormalities in PSS patients, while this was present in RA patients (p less than 0.001). CCTA were always negative in 18 patients with systemic lupus erythematosus and were found in one out of 8 cases with Sjogren's syndrome, also positive for rheumatoid factor without clinical RA. These data suggest that CCTA are evoked when involvement of cardiac conducting tissue (as in RA) or working myocardium (as in PSS) is present. Whether CCTA should be mainly regarded as an expression of the immunological derangement underlying these pathological conditions or whether they are secondary to myocardial tissue damage, must still be clarified. PMID- 4017311 TI - Male patients with Behcet's syndrome have stronger pathergy reactions. AB - The effects of patient's sex and age at onset on the pathergy reaction (cutaneous hypersensitivity to a needle prick) and its correlation with disease activity in Behcet's syndrome was investigated by two independent observers in a blind protocol. Among 92 male patients the pathergy reaction was more strongly positive (p less than 0.025) than among 67 female patients of similar age and disease duration. The age at onset did not affect the severity of the pathergy reaction, although, the early onset females (age at onset 24 years or less) had the lowest prevalence of pathergy positivity (52%), compared to early onset males and late onset (age at onset 25 years or more) males and females (73-75%). As previously reported the disease was more severe among males and among those with early onset of either gender. On the other hand, no correlation between the strength of the pathergy reaction and clinical severity could be discerned. PMID- 4017312 TI - Mineral metabolism and bone mineral content in rheumatoid arthritis. Effect of corticosteroids. AB - An evaluation of mineral metabolism was performed in 41 patients with RA and the pertinent data were compared to bone mineral content in patients either untreated or treated with different doses of corticosteroids. Our study confirms that osteoporosis is a common finding even in rheumatoid patients never treated with corticosteroids. Moreover, in patients treated with such drug the loss of bone mineral content was related to the dosage rather than to the length of treatment. In all cases no overt biochemical derangement was observed. According to our study, parathyroid hormone does not seem to influence the development of osteoporosis in rheumatoid arthritis, while a relative deficiency of calcitonin along with an inadequate vitamin D metabolism could play some role. PMID- 4017313 TI - Rheumatoid factor isotypes following immunization. AB - Serum from 422 healthy subjects prior to and four weeks after multiple immunizations was studied for rheumatoid factors (RF) by an enzyme-linked immunosorbent assay (ELISA). Increase in IgM RF was detected in 22% of subjects by ELISA, but was not detectable by a standard sheep-cell agglutination test. Immunization may be a cause of RF positivity by a sensitive assay such as ELISA; it is not likely to be detected by standard clinical methods. PMID- 4017314 TI - Credibility of placebo transcutaneous nerve stimulation and acupuncture. AB - In a study comparing the credibility of acupuncture and sham transcutaneous nerve stimulation (TNS) within a group of chronic pain patients, equal suggestion of the sham TNS was achieved by incorporating a visual display and strong verbal suggestion into the placebo treatment. The analgesic effect of placebo is a confounding factor in controlled trials of physical methods of pain relief, and the use of sham therapy distinguishable from active therapy requires that the placebo be validated as a true control for the non-specific components that constitute the placebo aspect of the active treatment. This study uses a questionnaire designed to assess patient expectancy of effectiveness and concludes that sham TNS with strong visual and verbal suggestion may be a valid placebo for controlled studies of the analgesic effect of acupuncture. PMID- 4017315 TI - Clavicular periosteal new bone formation in ulcerative colitis. AB - A case of painful periosteal new bone formation is described in the clavicles of a 26-year-old man suffering from ulcerative colitis. Histology showed non specific osteitis, with signs of new bone formation. The clavicular pain regressed during treatment of the bowel inflammation. PMID- 4017316 TI - Gold nephropathy and renal amyloidosis in a patient with rheumatoid arthritis. AB - A 71-year-old Caucasian woman with rheumatoid arthritis, who had been treated with gold salts for 19 months, developed a significant proteinuria associated with nephrotic syndrome and renal impairment. Her renal biopsy revealed the unusual simultaneous occurrence of gold nephropathy and renal amyloidosis and she was treated by gold withdrawal, methylprednisolone pulses and azathioprine, with a good remission of symptoms. We describe the case and discuss the possible cause(s) of similar renal involvement and the results obtained with the combined therapy of steroids and cytotoxic drugs. PMID- 4017317 TI - Suggestibility and placebo effect. PMID- 4017318 TI - Significance of the hydrogen ion concentration in synovial fluid in rheumatoid arthritis. AB - The hydrogen ion (H+) concentration and pCO2 were measured in the synovial fluid (SF) from the knee joints of 130 patients with arthritis by an acid-base analyser (ABL2 Acid-Base Laboratory), using a simple technique which prevented contact with air. H+ concentration was significantly higher in SF from 60 RA patients (mean 64.4 n mol/l; range 38-142 n mol/l) compared with patients with OA (mean 44 n mol/l; range 29-56 n mol/l), and 40 with other arthritides (mean 52 n mol/l). The H+ concentration in the SF showed a significant association with other variables of local inflammation-platelet, total leucocyte and polymorph counts, 5 nucleotidase, acid phosphatase and IgA levels in the SF and the clinical knee score, but not with the volume of the effusion. A similar relationship between these variables of inflammatory activity and SF pCO2 was also established. A higher SF H+ concentration was also found in systemically active disease, but no difference in SF pH between seropositive and seronegative patients. Whilst the pH of SF approximated to that of the blood in OA, it was significantly lower in the SF in RA. SF pH is a useful marker of local inflammatory activity, and its measurement is simple, reliable and rapid. It is relevant because changes in pH influence many of the processes involved in inflammation and the pH difference between SF and blood influences the transfer of drugs into the joint. PMID- 4017319 TI - Morphologic changes in the renal tract in pregnancy. AB - The morphology of the urinary tract is altered considerably during gestation. Changes occur as early as the first trimester and increase as pregnancy progresses. The edema and hyperemia that occur in the bladder along with its decreased tone predispose the patient to asymptomatic bacteriuria. The bacteria can then be transmitted to the ureters via the vesicoureteral reflux. The increase in urinary volume in the ureteropelvic system enhances the growth of the organisms and hence is thought to be the major cause of the increased incidence of pyelonephritis in pregnancy. The morphologic alterations regress dramatically as pregnancy is terminated and reach prepregnancy status at most by the third month post partum, a fact of which clinicians should be aware when interpreting diagnostic test results. PMID- 4017320 TI - The physiology of the renal tract in pregnancy. PMID- 4017321 TI - Acute urinary tract infections in pregnancy. AB - Routine screening for pregnancy ASB followed by adequate therapy and urine culture surveillance are important preventative measures which should be practiced by all obstetric physicians. The considerable maternal morbidity associated with the development of acute pyelonephritis more than justifies the effort and expense necessary to implement screening methods for the detection of ASB. A variety of simplified culture techniques are available for office or clinic use which are inexpensive and correlate well with the more expensive standard bacteriologic methods employed by diagnostic laboratories. PMID- 4017322 TI - Assessment and treatment of renal disease in pregnancy. PMID- 4017323 TI - Postpartum evaluation of renal function. PMID- 4017324 TI - Septic shock in the gynecologic patient. PMID- 4017325 TI - Torsion of the adnexa. AB - Adnexal torsion is an interesting, uncommon, and potentially lethal condition that may arise most unexpectedly in women of any age, but particularly during the reproductive years. It is generally unilateral and may involve either normal or pathologically enlarged ovary or tube, or both organs. The condition may be partial or complete, the latter often resulting in gangrene and marked exacerbation of symptoms. If untreated, it may progress to necrosis and gangrene, followed by peritonitis, which may be lethal. Prompt diagnosis, in which timely diagnostic laparoscopy and ultrasound evaluation of the pelvis may be helpful, provides the opportunity for prompt laparotomy with untwisting of the torsion and stabilization of the adnexa by suture and cystectomy, if possible, extirpation if not. Organ conservation requires a clear need to preserve reproductive or ovarian function, so cystectomy is generally preferable to oophorectomy. PMID- 4017326 TI - Prolonged survival without neurologic deficit following traumatic dorsolateral brainstem injury. AB - A 25-year-old white male survived a closed head injury with brainstem damage for two years without major neurologic deficits and succumbed to an unrelated condition. Gross and microscopic study of quantity and distribution of his lesions suggest that one-sided lateral brainstem injury of traumatic nature may be compatible with long survival and only minor neurologic deficit. Future cases should be evaluated for the validity of this hypothesis. PMID- 4017327 TI - Experimental freeze-preservation of chondrocytes. AB - Preservation of articular cartilage chondrocytes is currently being investigated in conjunction with storage and transplantation of osteochondral allografts. Studies on isolated chondrocytes have suggested that viability and function may be retained following freeze-preservation. Up to 90% of frozen isolated cells will survive, and these cells are capable of producing proteoglycans in culture. Results of freezing chondrocytes in a matrix have not been as successful, with viability ranging from 0% to 50%. Inconsistent results are thought to be due to the matrix and associated problems such as poor penetration of the cryopreservative, an unequal rate of cooling, and a high water content. Studies are in progress in an attempt to produce a satisfactory method of freeze preservation that will promote normal functioning of chondrocytes after transplantation in an articular cartilage matrix. PMID- 4017328 TI - Bone allografts in salvage of difficult hip arthroplasties. AB - Fourteen bone allograft transplantations were performed in 12 patients: five whole-hip osteoarticular allografts, eight acetabular wall, and one proximal femur with long-stem prosthesis. Average followup time was 19 months. Average patient age was 46 years. Acetabular grafts appeared healed. There was narrowing of joint space in all whole-hip allografts. However, joint narrowing did not correlate with functional results. Failures were attributed to collapse of the femoral head in one patient and nonunion at the host-allograft junction in two patients. However, even in primary failures, allografts provided bone stock to substitute for massive bone loss; this allowed for further reconstruction with endoprostheses. Intercalary segmental allografts combined with prosthetic devices gave the best results. PMID- 4017329 TI - Cadaveric elbow allografts. A six-year experience. AB - Transplantation of total elbow allografts has been employed as a salvage procedure in an attempt to provide patients with a useful, painless range of motion of the elbow. Patients who are candidates for this procedure include those with disabling elbow joint symptoms who refuse an arthrodesis or are not candidates for conventional total elbow replacement because of excessive bone loss or young age. Allografts must be subjected to rigid internal fixation. Rush rod fixation used early in this series was associated with a high incidence of nonunion. In this series, ten patients followed for one to six years were provided with a functional elbow. However, long-term results are still unknown. Although not recommended for routine use, this operation is viewed as a salvage procedure. The use of allografts in elbow reconstruction does not preclude subsequent reconstruction with another allograft or fusion. In patients with deficient bone stock, the allografts reestablish bone mass to permit an arthrodesis or reconstructive arthroplasty. PMID- 4017330 TI - Hypothermic storage and cryopreservation of cartilage. An experimental study. AB - Osteochondral autografts of femoral condyles in dogs were frozen at different cooling velocities after exposure to either glycerol or dimethyl sulfoxide to determine the freezing regimen best suited for preservation of intact cartilage. Autografts were also subjected to hypothermic storage in tissue culture media for ascertainment of how long they can be stored under these conditions. Autografts maintained in vitro under various conditions of storage were examined after transplantation. Autografts were chosen for this portion of the investigation in order to study the effects of storage uncomplicated by immunologic interactions. No differences were found between the cryoprotective actions of glycerol and dimethyl sulfoxide. The freezing rate that produced the least damage in the cartilage was 2 degrees/min. Cartilage survived ten days of hypothermic storage in tissue culture medium. Allografts frozen by the standard method of glycerolization and cooling at 1 degree/min were also studied. These showed eventual loss of chondrocytes and conversion of hyaline cartilage to fibrocartilage. PMID- 4017331 TI - Localization of symptomatic lumbar pseudarthroses by use of discography. AB - Twenty-four patients with lumbar pseudarthroses following attempted fusion were investigated by preoperative discography. The pseudarthroses were confirmed at surgical exploration. In 19 patients, discography at the level of a pseudarthrosis reproduced typical back pain, and in two patients the level above the fusion reproduced typical pain. Discography is not indicated when the major symptoms are leg or buttock pain. Technical errors included injection into the annulus fibrosis and impingement of the needle into the vertebral endplate. The latter may produce a false-positive result. Previous posterior fusions and very narrow disc spaces prevented insertion of the needle in some patients. Not all lumbar pseudarthroses were symptomatic, and two frequently occurred in the same patient. Discography is a useful adjunct to the traditional investigation of lumbar pseudarthroses. PMID- 4017332 TI - Granular cell ameloblastoma of the mandible with metastasis to the third thoracic vertebra. A case report. AB - A 62-year-old housewife had a metastasis of granular cell ameloblastoma to the third thoracic vertebra. She had suffered at least four local recurrences during the 38-year duration of the right mandibular tumor and was treated by posterior decompression of the spinal cord with instrumentation. Histologically, the granular cells appeared to be of epithelial origin. Ultrastructurally, the granules were identified as lysosomes, including some that were autophagic. Of 45 reported cases of granular cell ameloblastoma, there have been only three cases with pathologically confirmed metastasis. Their characteristics are long duration of the tumor, multiple local recurrences, and predominance in blacks. PMID- 4017333 TI - Abductor muscle performance in total hip arthroplasty with and without trochanteric osteotomy. Radiographic and mechanical analyses. AB - Total hip arthroplasty was performed for unilateral hip disease in 26 patients with trochanteric osteotomy (TS) and 27 patients without osteotomy (NS). Early postoperative recovery of function, pain, mobility, radiographic changes, and abduction torques were recorded and evaluated. Theoretic analysis of hip mechanics based on radiographic measurements was compared with measured abduction torques for each patient. Function, pain, and mobility ratings were similar for both groups pre- and postoperation. Radiographic measurements demonstrated better mechanical reconstruction of hips in both groups. There was a trend, but no statistically significant correlation, of mechanical parameters and measured isokinetic or isometric abduction torques at the hip joint in the TS group. In the NS group, no correlation was found between mechanical parameters and measured torques. A significant improvement in recovery of torque was found in the NS group when compared to the TS patients. PMID- 4017334 TI - Treatment of femoral shaft fractures associated with acute spinal cord injuries. AB - Twenty-seven femoral shaft fractures in 23 patients with acute spinal cord injuries were reviewed for evaluation of the outcome of operative versus nonoperative treatment. Three groups were identified: 11 nonoperative, eight early operative, and eight delayed operative. Patients treated initially by nonoperative methods developed five impending nonunions (31%), which subsequently were treated by open reduction and internal fixation. One femur in each of the operative groups developed a refracture after early removal of metal fixation devices. In the delayed operative group, four patients (50%) required manipulation under general anesthesia for treatment of poor knee motion. Patients with complete neurologic lesions whose femurs were treated nonoperatively incurred more complications, i.e., decubitus ulcers, than those treated operatively. Operative stabilization of the femur within six weeks of injury rendered the most favorable outcome with the least number of orthopedic or medical complications in patients with both complete and incomplete cord lesions. All of the eight fractures united. PMID- 4017335 TI - Histologic evidence of retinacular nerve injury associated with patellofemoral malalignment. AB - Patellofemoral malalignment is frequently accompanied by pain that may respond to conservative treatment or lateral retinacular release. Frequently, there is little or no evidence of chondromalacia patellae in these patients. This study presents consistent evidence of nerve damage (demyelination and fibrosis) in the lateral retinaculum of patients with intractable patellofemoral pain requiring lateral retinacular release or realignment of the patellofemoral joint. The changes observed in the retinacular nerves resemble the histopathologic picture of Morton's interdigital neuroma. It is likely that the lateral retinaculum itself is painful in many patients with patellofemoral malalignment. PMID- 4017336 TI - Knee fusion with intramedullary rods for failed total knee arthroplasty. AB - Knee fusion was obtained after failed total knee arthroplasty with the aid of internal fixation by use of intramedullary rods. The method has been used in eight cases, including difficult situations characterized by morbid obesity, segmental fractures, and loss of bone stock. In these cases, stability would have been difficult to obtain with conventional methods of external fixation, compression, or casting. Stability was achieved quickly with an intramedullary rod in eight cases; fusion was obtained in seven. PMID- 4017337 TI - Combined Maquet and proximal tibial valgus osteotomy. AB - A combined Maquet and proximal tibial valgus osteotomy has been used to treat patients presenting with anterior and medial compartmental degenerative arthritis. Patients with clinically symptomatic lateral compartmental disease, gross instability, or a nonfunctional range of motion were excluded. Thirty-four knees in 31 patients whose average age was 59.6 years were studied. Follow-up periods range from six to 36 months (mean, 16 months). Results have been tabulated with respect to the patient's preoperative radiographs and clinical knee ratings. The surgical technique has been the same throughout the series and is notable for the absence of metallic fixation and for the division of the tibiofibular joint proximally without an associated fibular osteotomy. Neither nonunion nor peroneal nerve dysfunction was encountered postoperation. To date, 68% of the results have been graded as good to excellent, 20% as fair, and 12% have failed. No correlation was found between preoperative radiographic rating and postoperative result. PMID- 4017338 TI - Distal calcaneal osteotomy in resistant talipes equinovarus. AB - In resistant talipes equinovarus deformity, posterior medial release alone may be inadequate. Procedures involving the lateral column are sometimes necessary. Thirty-nine patients were treated by a distal calcaneal osteotomy and plantar fasciotomy. Good results were obtained in 30 of 39 patients; two had fair results and seven of 39 had poor results. Of the lateral column procedures, distal calcaneal osteotomy avoids the articular surfaces and provides for easier rotational positioning and correction of the forefoot. Older patients who have had multiple operations and, potentially, more severe pathology do not do well with this procedure. Preoperative evaluation of certain radiographic parameters is important in patient selection for these procedures. PMID- 4017339 TI - Clinical and neurophysiologic characteristics of the pronator syndrome. AB - Nine patients were clinically diagnosed as having a pronator syndrome, i.e., high median nerve compression. The main symptom was pain at the proximal volar aspect of the forearm increasing for several hours after exercise. All patients showed local tenderness over the median nerve 4-5 cm distal to the elbow and pain on active forearm pronation against resistance. Two patients had been previously operated upon for carpal tunnel syndrome. Preoperative routine neurographic electromyographic studies were normal. In the differential diagnosis, the exclusion of carpal tunnel syndrome and anterior interosseous nerve entrapment is most important. On active isometric forearm pronation, interference with median nerve motor conduction occurred in three patients preoperation. This phenomenon had disappeared following median nerve decompression at the level of the pronator muscle. Fibrous bands from the pronator muscle, encircling the nerve, seemed to be an etiological factor. Eight of nine patients were either improved or recovered completely by surgical treatment. PMID- 4017340 TI - Radiocarpal fracture--dislocation. AB - Radiocarpal fracture-dislocation was associated with fracture of the distal articular surface of the radius in five patients (six extremities). Closed manipulation resulted in satisfactory reduction of both the dorsal dislocation of the carpus on the distal radius and displaced articular fracture fragment(s) in two of four extremities. In four extremities, open reduction was necessary as the only means of satisfactorily managing this severe wrist injury. Direct visualization through a dorsolateral incision alone allows for maximal restoration of the often extensive bony injury of the dorsal articular surface of the radius. A volar incision is required for anatomic reduction of the carpus, and median reconstitution of the radiocarpal ligament nerve decompression. Functional results were generally satisfactory; however, radiographic degenerative changes appearing early portend traumatic arthritis as a sequela of this complex injury. PMID- 4017341 TI - Bioresorption of ceramic strontium-85-labeled calcium phosphate implants in dog femora. A pilot study to quantitate bioresorption of ceramic implants of hydroxyapatite and tricalcium orthophosphate in vivo. AB - Ceramic hydroxyapatite and tricalcium orthophosphate were radioactively labeled with their strontium-85 analogs. Porous blocks of these materials (dimensions 2.5 X 1.25 X 0.5 cm) were implanted into surgically created defects in dog femora. The fate of the implants was studied by roentgenography, radioactivity measurements, histology, and microradiography. The radioactivity over the implant site was followed for 22 weeks. Implants were retrieved after 20-25 and 50-55 weeks. Hydroxyapatite implants were not affected by biodegradation processes, while tricalcium orthophosphate implants were subject to extensive bioresorption (25%-30% in 22 weeks). Resorption debris from tricalcium orthophosphate implants was found in mononuclear phagocytes and multinuclear osteoclastlike cells. The supposition is that tricalcium orthophosphate is transformed into hydroxyapatite in a physiologic environment. Labeling of ceramic calcium phosphate implants with strontium-85 analogs offers an adequate technique to quantitate bioresorption in vivo. PMID- 4017342 TI - The effect of manganese ingestion, phosphate depletion, and starvation on the morphology of the epiphyseal growth plate. A stereologic study. AB - Oral administration of manganese to young rats results in poorly mineralized primary spongiosa and an irregularly thickened growth plate with a histologic resemblance to that in vitamin D-deficiency rickets. In the present study, the rachitic lesions were characterized by stereologic methods at the light microscopic level. With increasing doses of Mn in the diet, the animals developed rachitic lesions of increasing severity, i.e., the total height of the growth plate and the relative volume of the hypertrophic zone increased. The experimental animals developed hypophosphatemia, which was dependent on the Mn dose. The observed serum concentrations of Mn and phosphorus are compatible with the idea that MnHPO4 is precipitated in the gut, leaving only small amounts of Mn and phosphate available for absorption. Furthermore, the severity of the rachitic lesions were inversely correlated to the concentration of phosphate in serum. The most important pathomechanism in Mn rickets is phosphate depletion, which per se causes similar rachitic changes, even though Mn also seems to have other effects. Starvation caused a decrease in the height of the growth plate and in the volume fraction of the hypertrophic zone, thus changes contrary to the rachitic lesions. PMID- 4017343 TI - Decompression of an experimental compartment syndrome in dogs with hyaluronidase. AB - The treatment of compartment syndromes in which elevation of intracompartmental pressure occurs is by surgical fasciotomy. This is a relatively simple procedure but may be associated with complications. This study aimed at developing an alternative method to decompress a compartment by use of the enzyme hyaluronidase. Autologous plasma was infused into the anterolateral leg compartments of six dogs to simulate compartment syndromes of 80 mmHg. Pressure decay after pressurization was recorded. The compartment pressures were then again raised to 80 mmHg by subfascial injections of 1500 units hyaluronidase in 2 ml saline injected into one compartment and 2 ml saline only into the control side. Pressure decay was again recorded. On the experimental side, a significantly faster decay rate occurred after hyaluronidase injection than after initial pressurization; 8.0 +/- 1.3 (S.E.M.) versus 3.4 +/- 0.4 (S.E.M.) mmHg/min (p less than .01). Pressure decay after hyaluronidase injection was significantly faster than after the same volume injection on the control side, over both a four minute period (8.0 +/- 1.3 [S.E.M.] versus 4.1 +/- 0.6 [S.E.M.] mmHg/min [p less than .03]) and a 25-minute period (2.1 +/- 0.3 [S.E.M.] versus 1.3 +/- 0.1 [S.E.M.] mmHg/min [p less than .03]). Hyaluronidase removes hyaluronic acid molecules from the leg compartment fascia and, by facilitating fluid flow from the compartment, causes decompression. Hyaluronidase may then have a place in the prophylaxis and treatment of compartment syndrome, thus avoiding anesthesia and surgery. PMID- 4017344 TI - Induced regeneration of calvaria by bone morphogenetic protein (BMP) in dogs. AB - In the adult dog, a 14-mm skull trephine defect regenerates only incompletely in the lifetime of the individual. Only about half of the defect is repaired; the regenerated part develops by extension of growth from the bony rim. Correlated roentgenographic and histomorphometric methods demonstrate that new bone develops by proliferation of preexisting osteoprogenitor cells lining the diploe and perivascular cells of the bone marrow stroma. An autogeneic bone graft, including bone marrow, provides a supplementary supply of cells in a homostructural framework and generally completes the repair process. Transplants of bone marrow alone fail to repair the defect. Implants of bovine bone morphogenetic protein (bBMP) and a carrier consisting of matrix gamma-carboxyglutamic acid rich protein (without any additional bone or bone marrow) induce repair almost as completely as an autograft. BMP-induced bone regeneration is incomplete in the thin lateral temporal marrow-deficient part of the cranium. Implants of BMP plus bone marrow induce complete repair, suggesting that calvarial bone regeneration is bone marrow stroma-dependent for a supply of target cells. The target for BMP in cranial bone regeneration is the perivascular connective tissue cells (pericyte) of the host bed marrow stroma and endosteum. The molecular mechanism of differentiation of pericytes into osteoprogenitor cells is not known, but the process is irreversible, heritable, and presents a solvable problem. PMID- 4017345 TI - Fate of vascularized and nonvascularized autografts. AB - Controlled laboratory data demonstrate biologic and mechanical characteristics of orthotopically placed canine ulnar autografts. The pattern of bone repair was similar in vascular and nonvascular ulnar grafts beginning with resorption followed by appositional reactive bone formation. The time intervals in the sequence were accelerated in the vascularized grafts. Both the strength and stiffness of the vascularized grafts were found to be significantly greater in Groups studied from six weeks to six months postoperation. There was no statistical difference between the grafts for mechanical testing performed on dogs either one week or one year postoperation. The vascularized ulnar bone grafts fared better than comparably sized nonvascularized grafts and were more rapidly repaired. The mechanical testing demonstrated superior strength and stiffness of the vascularized grafts throughout the repair process. PMID- 4017346 TI - [Postural responses to a sudden forward tilting force in Parkinson's disease- analysis of surface electromyograms of leg muscles and in silent periods]. PMID- 4017347 TI - [An atypical case of Cockayne syndrome showing a decrease in cultured skin fibroblast colonies by ultraviolet irradiation]. PMID- 4017348 TI - [A case of Kearns-Sayre syndrome with elevated lactate and pyruvate levels in the cerebrospinal fluid]. PMID- 4017349 TI - [Restless legs syndrome in four parkinsonian patients treated with amantadine]. PMID- 4017350 TI - [Neurological disorders and sweating. I. Sweating disturbances in unilateral vascular lesions of the brain stem]. PMID- 4017351 TI - [Structural proteins of the opaque muscle fibers in Duchenne muscular dystrophy]. PMID- 4017352 TI - [Nuclear magnetic resonance imaging in multiple sclerosis]. PMID- 4017353 TI - [Sensory nerve conduction by the medial antebrachial cutaneous nerve]. PMID- 4017355 TI - [Epidemiologic study of myopathy in Kumamoto Prefecture]. PMID- 4017354 TI - [Neurogenic proximal muscular atrophy with rigid spine]. PMID- 4017356 TI - [Herpetic brainstem encephalitis--a case report]. PMID- 4017357 TI - [A study of exercise-induced muscular changes in rats]. PMID- 4017358 TI - [Mitochondrial encephalomyopathy: a case with MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes)]. PMID- 4017359 TI - [Two cases of syringomyelia showing atypical neurological sings]. PMID- 4017360 TI - [The orbicularis oris reflex and the orbicularis oculi reflex]. PMID- 4017361 TI - [Pseudohypoparathyroidism associated with amyotrophic lateral sclerosis (ALS) syndrome]. PMID- 4017362 TI - [Changes of silent periods in normal gastrosoleus muscle under the upright position at tilting board]. PMID- 4017363 TI - [An autopsy case with meningitis accompanied by circumscribed spinal cord damage]. PMID- 4017365 TI - [Masticatory spasm in progressive facial hemiatrophy]. PMID- 4017364 TI - [Subacute combined degeneration of spinal cord. Significance of peripheral nerve involvement]. PMID- 4017366 TI - [Clinicopathological study on eye movement of progressive supranuclear palsy]. PMID- 4017367 TI - [A clinical study for pathogenesis of idiopathic peripheral facial palsy]. PMID- 4017368 TI - [Diagnosis of the Wernicke's encephalopathy]. PMID- 4017369 TI - [An observation of spontaneous discharges by surface EMG in motor neuron disease. Correlation between ratio of evocation by edrophonium and clinical course]. PMID- 4017370 TI - [Kearns-Sayre syndrome with reduced cerebrospinal fluid folic acid]. PMID- 4017371 TI - [A prolapsed cervical disc with diffuse contrast enhancement on CT]. PMID- 4017372 TI - [Midbrain corectopia. A manifestation of dorsal midbrain syndrome in seven patients with basilar artery infarction]. PMID- 4017373 TI - [Duchenne muscular dystrophy in a female with an X-autosome translocation]. PMID- 4017374 TI - [Delayed radiation necrosis of the brain. A case with Kluver-Bucy syndrome]. PMID- 4017375 TI - [A case of callosal apraxia after left anterior cerebral artery occlusion]. PMID- 4017376 TI - [Elevation in upper part of trapezius muscles in FSH muscular dystrophy]. PMID- 4017377 TI - [A case of total agenesis of the corpus callosum. The diagnosis by NMR-CT and the localization of the speech center]. PMID- 4017378 TI - [A case of spindle coma]. PMID- 4017379 TI - Rapid resolution of perfusion/ventilatory abnormalities in pulmonary air embolism. AB - A case of pulmonary air embolism is presented demonstrating a nearly total lung perfusion defect and a matching ventilation deficit. Despite advanced age, mild chronic obstructive airway disease, and congestive heart failure, the perfusion/ventilatory (V/Q) abnormalities produced by the air emboli resolved to near completion within three days. Rapid resolution of V/Q abnormalities due to air embolism is distinct when compared to the abnormalities seen with thromboembolism and the mechanism the matching V/Q defects is discussed. PMID- 4017380 TI - Practical hepatobiliary imaging using pretreatment with sincalide in 139 hepatobiliary studies. AB - Hepatobiliary studies were performed over a three-year period on 139 patients suspected of having cystic duct obstruction. Each patient was infused intravenously with sincalide, a C-terminal octapeptide of CCK, 15 minutes prior to the administration of the hepatobiliary imaging agent Tc-99m paraisopropyl iminodiacetic acid (PIPIDA). Analysis of the results demonstrated significant advantages in pretreating patients with sincalide in hepatobiliary studies in a small facility with a relatively large patient load. Most of our studies were completed within 2 hours without jeopardizing the sensitivity (97%) or accuracy (96%) of the test. The specificity (88%) was comparable to percentages reported by others. Most investigators have reported that chronic cholecystitis contributed to the majority of false-positive cases. In addition, inconsistency in the documentation of criteria for the determination of acute cholecystitis (surgical, radiologic, or histologic also could be a cause for such a discrepancy. Knowledge of some important variables may help improve the specificity of the test: an awareness of the following factors during scan interpretation: 1) the effectiveness of the sincalide pretreatment dose, 2) the patient's pretest status (fasting or nonfasting, postanalgesic medication or no analgesics), and 3) time limit for gallbladder visualization. With these variables in mind, the hepatobiliary imaging using pretreatment with sincalide is proven to be a practical procedure protocol with good sensitivity and accuracy as well as specificity. PMID- 4017381 TI - Amiodarone-induced hyperthyroidism in a patient with Marfan's syndrome and Wolff Parkinson-White syndrome. AB - In a 20-year-old patient with Marfan's syndrome and Wolff-Parkinson-White syndrome, effective amiodarone treatment had to be stopped due to serious hyperthyroidism. Diagnosis and therapy of amiodarone-induced dysthyroidism is discussed. PMID- 4017382 TI - Combined delayed technetium-99m HIDA and technetium-99m tin colloid diagnosing liver deformity due to hepatic flexure. PMID- 4017383 TI - Diffuse bone metastases in a case of astrocytoma. AB - Presented is an unusual case of astrocytoma with diffuse multiple bony metastases in bone imaging. The classification, spread, and prognosis of astrocytoma are briefly reviewed. PMID- 4017384 TI - Renal and hepatic scintigraphy in paroxysmal nocturnal hemoglobinuria (PNH). AB - Scintigraphic findings in paroxysmal nocturnal hemoglobinuria (PNH) have been presented. To summarize, a focal hot spot on liver imaging was better seen on the IDA scan, showing resolution following a satisfactory portacaval anastomosis. PNH is another cause of hot kidneys on bone imaging. PMID- 4017385 TI - The development of regenerative nodules in Budd-Chiari syndrome demonstrated by liver scan. PMID- 4017386 TI - "Positive" gallium scan of chest secondary to colonic herniation. PMID- 4017387 TI - False-positive liver scintigraphy secondary to posterior sulcus pulmonary neoplasm. PMID- 4017388 TI - False-positive liver scan due to ascites. PMID- 4017389 TI - Subintimal dissection of peritoneovenous shunt tubing. Demonstration with radionuclide study. AB - A case report is presented in which malfunction of a peritoneovenous shunt was caused by subintimal dissection of the venous end of the shunt tubing. The radionuclide shunt patency study demonstrated a collection of radioactivity at the venous end of the tubing, representing the abnormal intramural collection of peritoneal fluid. Scintigraphic demonstration of this complication of a peritoneovenous shunt has not been reported previously. PMID- 4017390 TI - Bile ascites in adults. Diagnosis using hepatobiliary scintigraphy and paracentesis. AB - Hepatobiliary scintigraphy has been recognized as a useful diagnostic tool in detecting the presence and site of bile leaks. The authors report a case of bile ascites secondary to a postsurgical biliary leak, the scintigraphic findings in bile ascites, and the potential use of paracentesis, in combination with hepatobiliary scintigraphy, in confirming the presence of bile ascites and a bile leak. PMID- 4017391 TI - Demonstration of a false-positive lesion on indium-111 leukocyte scintigraphy in a case of active Crohn's disease. AB - Increased fecal excretion of In-111 tagged leukocytes in patients with active inflammatory bowel disease may lead to a false-positive site of disease in patients with a diverting colostomy or ileostomy and fecal collection bags that overlie the abdominal wall or groin region. PMID- 4017392 TI - Scintigraphic visualization of human malignant melanoma with N-isopropyl-P-[I 123] iodoamphetamine. AB - Marked accumulation of I-123 IMP was noted in a patient with malignant melanoma. This preliminary finding suggests the potential role of I-123 IMP for detection and evaluation of the disease. PMID- 4017393 TI - Transient bronchoconstriction associated with angiographically proven pulmonary embolus. AB - It is rare for a pulmonary embolus to cause delayed washout on xenon scans. A case of angiographically proven pulmonary embolus with transient bronchospasm present 48 hours after the onset of symptoms is presented. Possible mechanisms are discussed. PMID- 4017394 TI - The role of nuclear imaging in the management of the first total artificial heart recipient. AB - On December 2, 1982, a permanent total artificial heart was implanted into the chest of a 61-year-old man with a progressive and irreversible cardiomyopathy. During the ensuing four-month hospitalization, a number of nuclear medicine procedures were obtained to assist in patient management. These procedures included gated cardiac radionuclide ventriculography, an I-123 iodoamphetamine scan for cerebral perfusion, and In-111 labeled leukocyte imaging. These radionuclide studies demonstrate the advantages of being able to monitor physiologic changes noninvasively and illustrate a potential role for nuclear cardiology in managing patients with a total artificial heart. PMID- 4017395 TI - Idiopathic pulmonary ossification with focal pulmonary uptake of technetium-99m HMDP bone scanning agent. PMID- 4017396 TI - Gastrointestinal blood pool imaging in tuberous sclerosis. PMID- 4017397 TI - Pemoline pharmacokinetics and long term therapy in children with attention deficit disorder and hyperactivity. AB - The pharmacokinetic behaviour of pemoline was studied in 28 children, aged 5 to 12 years, diagnosed as having the attention deficit disorder with hyperactivity. The mean elimination half-life of pemoline in these children was approximately 7 hours, which is considerably shorter than the half-life of 11 to 13 hours previously reported in adults. The tendency of the half-life to increase with age may be explained by the statistically significant decrease in total body clearance with age. The increasing half-life of pemoline with age should be considered during long term drug therapy. In this study no tolerance to the beneficial effects of pemoline was observed over 6 months. The apparent therapeutic serum concentration range for these children was attained after doses of 37.5 to 131.25 mg pemoline daily. Since the optimum serum concentration shows wide variation, the dosing regimen must be determined individually. Routine monitoring of the pemoline serum concentrations is not useful because of this apparent variation in optimum serum concentration and because of the linear relationship between dose and concentration. PMID- 4017399 TI - Nonparametric methods. Clinical applications. AB - In clinical research, "samples" are studied in order to get ideas about the characteristics of the larger populations from which the samples are taken. Population characteristics are called parameters (the population mean and standard deviation are examples). Parametric statistical methods are those that require estimates of parameters and assumptions about the source populations. Familiar examples of parametric methods are the t test, analysis of variance, and Pearson's correlation coefficient. Nonparametric (NP) methods do not require estimates of population parameters. These methods are sometimes called "distribution-free" because the samples of interest can be evaluated without concern for the shape (distribution) of the values in the populations providing the samples. NP methods also are called "ranking" or "ordering" tests, because the relative size or order of the observations may be evaluated, rather than requiring actual measurements. More than 30% of the research reports that appeared between July 1982 and June 1983, in four pediatric journals, employed at least one nonparametric method. The commonly used tests were chi-square, the Fisher exact test, and various "ranking" methods. An alphabetical list of common nonparametric tests is presented, with brief comments about each. Tables are presented, arranged by types of observations, so that the nature of the data guides the user to the method that might be used. PMID- 4017398 TI - Plasma concentrations of carbamazepine and carbamazepine 10,11-epoxide during pregnancy and after delivery. AB - Plasma concentrations of carbamazepine were monitored in 9 pregnant epileptic patients treated with the drug alone at constant doses during pregnancy and for at least 3 months after delivery. In addition, plasma concentrations of the metabolite, carbamazepine 10,11-epoxide were measured in 6 of the 9 patients. Plasma carbamazepine concentrations were fairly stable during pregnancy, and carbamazepine relative plasma clearances were significantly higher in weeks 4 to 24 than in weeks 25 to 32. After the end of the second trimester, there were no variations in plasma carbamazepine 10,11-epoxide concentrations and carbamazepine 10,11-epoxide:carbamazepine ratios. Both parameters were significantly higher in weeks 4 to 24 than in weeks 25 to 32 of pregnancy. PMID- 4017400 TI - Persistent hypertransaminasemia as the presenting finding of childhood muscle disease. AB - Four children with isolated, persistent elevations of serum transaminases were investigated for hepatic disease and followed for 4 to 24 months before serum creatine kinase determinations were obtained and found to be markedly elevated. Evidence of muscle disease was obtained by close questioning, retrospectively, and mild abnormalities were found on physical examination. Review of laboratory tests in our center for 6 months revealed 30 additional cases of anicteric hypertransaminasemia (20% of those with elevated enzymes), only two of which were unexplained by the admitting diagnosis. Serum transaminase values are elevated in a variety of diseases of different organ systems. Creatine kinase determinations may provide the clue to the diagnosis of occult muscle disease in some children with unexplained anicteric hypertransaminasemia. PMID- 4017401 TI - Respiratory complications of metatropic dwarfism. AB - Two infants with clinical and radiologic features of metatropic dwarfism presented in the neonatal period with episodes of cyanosis. Diagnostic studies to determine the etiology of these spells, including electrocardiogram, electroencephalogram, arterial blood gases, and metabolic and sepsis studies, were unremarkable. Chest roentgenograms revealed the characteristic long, narrow thoracic cage with no evidence of parenchymal disease. Cervical spine stability evaluation, pulmonary function studies, and chest impedance monitoring with qualitative air flow thermistor studies and transcutaneous oxygen monitoring were carried out. Both patients demonstrated a significant increase in resistance of the respiratory system following passive maneuvering of the head from a neutral position, suggestive of hypopharyngeal air flow obstruction. Obstructive sleep apnea resulting in cyanosis was documented in both patients. All other studies failed to yield a cause for the episodes of cyanosis. Our investigation failed to alter the clinical course which resulted in respiratory arrest and death by 7 months of age. A table is presented for the differentiation of skeletal dysplasias presenting in the perinatal period. PMID- 4017402 TI - Oculoglandular syndrome caused by Francisella tularensis. AB - Oculoglandular syndrome developed in a 9-year-old boy with a recent history of tick bites and minor eye trauma. Francisella tularensis was isolated on chemically supplemented chocolate agar from a swab of a conjunctival ulcer and an aspirate of a preauricular lymph node, confirming the diagnosis of tularemia. In addition, a rise in agglutination titer to the pathogen was detected in paired sera. The differential diagnosis of oculoglandular syndrome is discussed, with emphasis on the clinical characteristics which led to the diagnosis of tularemia. PMID- 4017403 TI - Subglottic laryngeal atresia associated with tracheoesophageal fistula. Long-term survival. PMID- 4017404 TI - The CHARGE association in a male newborn infant. Diagnostic and therapeutic considerations. PMID- 4017405 TI - Prenatal factors affecting intrauterine growth retardation. AB - Intrauterine growth retardation (IUGR), like postnatal growth retardation, involves skeletal and soft tissues. It is important to distinguish between depletion of soft tissues and stunting of linear skeletal growth, not only in older infants and children, but also in newborn infants. There are three main types of IUGR. To diagnose all three types involves much more than simply obtaining an individual's weight in relation to his or her age, as is now the widely accepted practice in newborn infants. Standards of intrauterine growth should not include growth-retarded newborn infants, insofar as it is possible to exclude them. Tables and graphs of intrauterine growth based on representative populations of newborn infants are apt to be a mixture of unknown numbers of normally grown and growth-retarded fetuses. The suggestion is put forward that standards of intrauterine growth should be based on newborn infants who have not been subjected to known growth-retarding influences prenatally. The diagnosis of intrauterine growth retardation prenatally by ultrasonic techniques has not reached the degree of reliability and validity that is needed for the routine detection of all fetuses with severe intrauterine growth retardation. Prenatal measurements made by ultrasound still require confirmation postnatally by appropriate measurements of infants at birth. The epidemiology, diagnosis, and postnatal courses of newborn infants with severe types of IUGR are discussed. PMID- 4017406 TI - Contemporary breast-feeding management. AB - This article updates clinicians in the successful initiation and practical management of nursing couples. Routine breast-feeding anticipatory guidance is provided, and specific problem-solving techniques offered for commonly encountered lactation problems. The physiologic basis of normal lactation is emphasized and related to specific problems. Issues addressed include the management of lactation in the presence of maternal employment, infant failure-to thrive, maternal drug therapy, and infant prematurity. PMID- 4017407 TI - Prenatal anticipatory guidance. AB - This article outlines the purpose and content of the prenatal visit. In question answer format, the article addresses the most frequently asked questions by the mother and the most relevant issues raised by the pediatrician. It is thus hoped that a flavor of both the process and goals of the prenatal visit will be conveyed. PMID- 4017408 TI - Group well-child care. AB - Well-child care can be a positive influence on parent-child relationships when social, psychological, and emotional health are stressed. Because of its brevity, the traditional well-child visit does not offer adequate opportunities to address these issues. A group format, in which four to six parent-infant pairs meet, changes the character of the child health maintenance visit. Advantages of group visits include increased time for patient education, more active parental participation, greater time for the physician to observe parents and their children, and more reassurance for parents that they and their children are normal. Problems of group visits are those of space and scheduling. Few pediatric offices have ideal space for group visits, so many visits take place in cramped quarters. Siblings can be disruptive to the group and should be excluded. A dedicated receptionist and an efficient nurse are essential if the groups are to run smoothly. Because the visits last one to one-and-one-half hours, only one group visit can be scheduled during a half day. Although parents of varied socioeconomic and cultural backgrounds benefit from group visits, this format appears to be most acceptable to white, middle-class families. The content of group visits is somewhat dependent upon parental questions and concerns; however, the physician must be careful to include important issues that do not usually arise spontaneously. These topics usually include safety, disease prevention, and anticipatory guidance. Although group visits may not fit every practice, the format does offer to both obstetricians and pediatricians some exciting possibilities. The increased patient-provider contact and the increased patient participation help establish better rapport, better educate families about health, and hopefully, will produce better babies. PMID- 4017409 TI - Perinatal coaching: program development. AB - Perinatal Coaching is a training/educational program introduced to new parents in the first days following the birth of their baby. This program provides support while teaching new parents skills to communicate and interact with their newborn following birth. The article gives an overview of the content of the Perinatal Coaching Program, a review of the newborn's capabilities and their relationship to perinatal coaching, important features of some ongoing programs, early identification and selection of parents, and speculation for future development. PMID- 4017410 TI - Enhancing the effectiveness of health education strategies. AB - Numerous articles have chronicled the problems that stem from patients' lack of compliance with health care recommendations, yet there has not been a systematic approach to the development of a strategy for increasing the effectiveness of health education programs. In this article, making use of anticipatory guidance, group well-child care, and injury prevention strategies, the author outlines several programs he has developed that can improve the effectiveness of health education strategies. PMID- 4017411 TI - Colic: excessive crying in newborns. AB - The pediatrician is commonly called upon to evaluate and manage the crying newborn. While most of these infants have colic, organic causes of crying must be carefully considered. The role of crying in precipitating child abuse also requires special vigilance on the physician's part. Colicky babies respond most effectively to physical contact and gentle motion. Other approaches, such as changing formulas or drugs, are unnecessary and potentially dangerous. Preventive measures for colic are addressed in steps one through four of the article "The Prevention of Sleep Problems" in this volume. PMID- 4017412 TI - The prevention of sleep problems. AB - The author offers guidelines that will help parents with the prevention of colic, trained night feeding, trained night crying, fearful night crying, bedtime temper tantrums, and bed-sharing. The information is presented chronologically by the visit at which it should be addressed. PMID- 4017413 TI - Twins and twin families. A practical guide to outpatient management. AB - Little has been written of a practical nature to guide the health professional in providing advice and support to families with twins in the practice setting. This article provides an overview of issues and concerns specific to twins and provides practical guidelines for caring for twins and their families. PMID- 4017414 TI - Metabolism of methoxyphenamine in extensive and poor metabolizers of debrisoquin. AB - Urine and plasma concentrations of methoxyphenamine (MP) and three of its metabolites were determined after a single oral 60.3 mg dose of MP hydrochloride to healthy subjects of known debrisoquin (D) phenotype. Urine was collected from five extensive (EM) and five poor (PM) metabolizers of D for 12 hours and analyzed after treatment with beta-glucuronidase/sulfatase. There were marked interphenotype differences in the total urinary excretion of O demethylmethoxyphenamine (ODMP) and 5-hydroxymethoxyphenamine (5HMP), as well as in MP/ODMP and MP/5HMP ratios. In contrast, the urinary output of N demethylmethoxyphenamine (NDMP) or MP/NDMP ratios showed no interphenotype differences. Plasma data from two EMs and two PMs showed that the mean values for maximum concentration t1/2, and total AUC for MP were two-, three-, and sixfold greater, respectively, in PMs than in EMs. The plasma levels of ODMP and 5HMP were higher in EMs than in PMs, whereas the converse was true for NDMP. Thus, O demethylation and aromatic 5-hydroxylation of MP are defective in PMs of D, resulting in increased MP and NDMP plasma levels. The form of cytochrome P-450 involved in the N-demethylation of MP is different from that responsible for O demethylation and aromatic 5-hydroxylation. PMID- 4017415 TI - Clinical pharmacology of timentin (ticarcillin and clavulanic acid). AB - Ticarcillin (4 gm) and clavulanic acid (0.1 gm) were simultaneously administered as timentin to patients with cancer as therapy for infections. The pharmacokinetics of both ticarcillin and clavulanic acid were studied in 15 patients after 30-minute and 2-hour intravenous infusions. The mean (+/- SD) ticarcillin plasma peak concentrations after the two infusions were 341 +/- 76 and 210 +/- 60 micrograms/ml. The plasma terminal t1/2 values of ticarcillin were 80 +/- 32 and 56 +/- 12 minutes. The AUCs were 631 +/- 189 and 601 +/- 230 mg/L X hr. The volumes of distribution of the area were 15 +/- 5 and 21 +/- 7 L and total clearances were 115 +/- 36 and 127 +/- 54 ml/min. The corresponding values for clavulanic acid after the infusions are as follows: mean peak concentrations, 5 +/- 1 and 4 +/- 1 micrograms/ml; plasma terminal t1/2 values, 84 +/- 24 and 74 +/- 36 minutes; AUCs, 11 +/- 3 and 11 +/- 6 mg/L X hr; volumes of distribution of the area, 22 +/- 3 and 32 +/- 6 L; and total clearances, 170 +/- 58 and 175 +/- 68 ml/min. PMID- 4017416 TI - Isosorbide dinitrate bioavailability, kinetics, and metabolism. AB - We studied the kinetics of isosorbide dinitrate (ISDN) after a dose of 5 mg iv and the bioavailability of a sublingual and an oral preparation of ISDN. Plasma levels of isosorbide 5-mononitrate (IS-5-MN), isosorbide 2-mononitrate (IS-2-MN), and ISDN were determined by GLC. After intravenous and sublingual dosing, ISDN plasma levels declined biexponentially and could adequately be described by an open two-compartment body model. Distribution was rapid; the t1/2 was 4.7 minutes after intravenous injection and 8.7 minutes after sublingual dosing. The volume of distribution at steady state was 90 L. The terminal disappearance t1/2 was 54.7 minutes after intravenous injection, 48.8 minutes after sublingual dosing, and 47.7 minutes after oral dosing. Total plasma clearance was 136 L/hr, exceeding normal liver plasma flow and indicating extrahepatic metabolism of ISDN. ISDN bioavailability after oral (10 mg) or sublingual dosing (10 mg) was similar (about 29%), indicating that the first-pass effect cannot be avoided by sublingual ISDN dosing. After intravenous ISDN, mononitrate plasma levels could be adequately described by another two-compartment body model. The terminal t1/2 was 4.33 hours for IS-5-MN and 1.83 hours for IS-2-MN. Noncompartmental calculations of the mononitrate levels revealed 100% systemic availability after oral and sublingual ISDN. We assume that ISDN was completely absorbed from the gastrointestinal tract, but 70% was metabolized during the first pass through the liver. After 5 mg iv ISDN, 16 mumol IS-5-MN and 5.3 mumol IS-2-MN reached systemic circulation. The entire dose of ISDN was converted to its two metabolites in a ratio of 3:1 (i.e., 75% IS-5-MN and 25% IS-2-MN). PMID- 4017418 TI - The effects of several weeks of ethanol consumption on ethanol kinetics in normal men and women. AB - We examined in normal men and women the effects of chronic ethanol consumption and the coadministration of cimetidine and ranitidine on the kinetics of ethanol. We found that the consumption of 45 gm ethanol per day for 3 weeks increased the apparent volume of distribution of ethanol in men from 732 to 884 ml/kg (P less than 0.01) but had no such effect in women (697 ml/kg before ethanol and 746 ml/kg after chronic ethanol consumption). This combined therapy had no effect on the rate of ethanol disappearance in either sex. In men the rate of disappearance was 165 mg/L/hr before and 168 mg/L/hr after chronic consumption, while in women the respective values were 209 and 203 mg/L/hr. The addition of either cimetidine or ranitidine had no effect on either parameter compared with values observed on day 22 of the study. In view of the known inhibitory effects of cimetidine on cytochrome P-450-dependent enzymes, our data suggest that this enzyme system does not metabolize a significant fraction of ingested ethanol in subjects who have consumed moderate doses of alcohol for several weeks. PMID- 4017417 TI - Moxalactam epimer disposition in patients undergoing continuous ambulatory peritoneal dialysis. AB - The kinetics of the epimers of moxalactam (R-MOX, S-MOX) were investigated in patients without infections who were receiving continuous ambulatory peritoneal dialysis after both intravenous and intraperitoneal injections of moxalactam. R MOX and S-MOX were well absorbed from the peritoneal cavity, with mean systemic availability of 0.71 +/- 0.18 and 0.79 +/- 0.18, respectively. After intravenous MOX, serum clearance was 10.2 +/- 3.4 (R-MOX) and 10.9 +/- 3.2 (S-MOX) ml/hr/kg. Net time-averaged peritoneal dialysis clearance of both epimers was minimal, about 10% of serum clearance. Serum and dialysate MOX concentrations were above the minimum inhibitory concentrations for susceptible bacteria for 24 hours after a 2.0 or 1.0 gm intravenous or intraperitoneal dose. Gastrointestinal side effects occurred after a 2.0 gm dose (both intravenous and intraperitoneal) but not after a 1.0 gm dose. There were no significant differences in the kinetics of R-MOX and S-MOX. A single 1.0 gm ip dose leads to serum and dialysate MOX concentrations above the minimum inhibitory concentration for susceptible pathogens for 24 hours. PMID- 4017419 TI - Cigarette smoking as a risk for cardiovascular disease. Part VI. Compensation with nicotine availability as a single variable. AB - In a biochemical investigation of human smoking behavior with filter cigarettes with high draw resistance that varied only in nicotine yield, we attempted to determine which nicotine levels provide desired nicotine intake with a minimum of physiologic and biochemical consequences. Twelve prescreened subjects were divided into two study groups and supplied with cigarettes that varied in nicotine delivery. Both groups were initially monitored while smoking their usual cigarette. At the following visit, smokers in group 1 received incremental increases and smokers in group 2 received incremental decreases in nicotine levels in assigned cigarettes. All subjects were monitored upon first exposure, after 1 week of acclimatization to each experimental cigarette, and upon return to their usual brands. Subjects in both groups were unable to compensate fully for their nicotine uptake from the lowest nicotine cigarette. In subjects in group 1, new nicotine baselines began to develop after 1 week of acclimatization to cigarettes containing 0.9 and 1.3 mg nicotine. New baseline nicotine levels were also noted in subjects receiving decreases in nicotine (group 2) after smoking the cigarette containing 1.3 mg nicotine for 1 week. Carboxyhemoglobin concentrations did not differ from those measured after the usual-brand cigarettes. Plasma cotinine concentrations increased as nicotine content per cigarette increased, except when subjects smoked a 1.3 mg nicotine cigarette. Plasma thiocyanate levels did not vary in either group. Systolic and diastolic blood pressures were generally not different from control values. PMID- 4017420 TI - A study of adverse reaction algorithms in a drug surveillance program. AB - To improve agreement among observers, several investigators have recently proposed methods (algorithms) to standardize assessments of causality for presumed adverse drug reactions. We evaluated one such method in the context of an intensive pediatric drug surveillance program. Four observers rated 50 randomly selected case reports drawn from the program, first using only general guidelines and then, several months later, using the strict criteria of the algorithm. Agreement among observers was poor in both study phases. The presence of selected characteristics of adverse events (e.g., major severity) did not improve agreement in either phase of the study. We conclude that routine use of such algorithms in drug surveillance programs is not likely to be of benefit. PMID- 4017421 TI - Losulazine, a new antihypertensive. AB - The efficacy of losulazine was determined in 32 patients with hypertension. Each subject was randomly assigned to receive either losulazine (n = 16) or placebo (n = 16) in a double-blind fashion. Losulazine in the dosage range of 10 to 30 mg b.i.d. effectively lowered the blood pressure. Diastolic blood pressure was lowered to less than or equal to 90 mm Hg in over 70% of the subjects receiving losulazine. There was no evidence of an increase in heart rate; to the contrary, there was a tendency for heart rate to decrease. Six subjects dropped out of the study before completion. Four of these were receiving placebo and dropped out because of lack of efficacy. One subject receiving losulazine dropped out for personal reasons during the first week of the study, and the other subject (also taking losulazine) dropped out when a drug-related pruritus (itchy eyes) developed. This event was readily reversed upon discontinuation of the drug. The drug was well tolerated and side effects were minimal, with no evidence of orthostatic effects or sexual dysfunction. There was a suggestion that nasal stuffiness and conjunctival congestion may be drug related. There were no changes in any laboratory values or body weight. PMID- 4017422 TI - Felodipine kinetics in healthy men. AB - In a randomized, crossover study, the absorption, distribution, and elimination of intravenous and oral felodipine were investigated in eight healthy men 22 to 31 years old. Felodipine was given as a 2.5 mg iv infusion over 30 minutes and as a 27.5 mg oral solution. Both doses were labeled with 25 microCi 14C-felodipine. Given as an oral solution, felodipine is rapidly (mean time to peak concentration 64 minutes; range 30 to 90 minutes) and completely absorbed. Presystemic elimination reduced the availability to 16% (range 10% to 25%). Felodipine kinetics can be described by a multicompartmental model with three distinct phases. The t1/2 for the initial phase was 6.4 minutes (range 1.7 to 10.4 minutes) and felodipine was distributed to a volume of 0.6 L/kg (range 0.4 to 0.9 L/kg), which approximately corresponds to the total body water. The second distribution phase reached pseudoequilibrium with a t1/2 of 1.6 hours (range 1.3 to 2.2 hours). The volume of distribution at the end of this phase was 9.7 L/kg (range 6.0 to 18.2 L/kg). The terminal phase had t1/2 of 10.2 hours (range 6.7 to 20.7 hours). The contribution of the three phases to the AUC was 15%, 40%, and 45% in the order of increased t1/2. Total body clearance of felodipine was 1.2 L/min (range 0.9 to 1.6 L/min). Within 72 hours after drug dosing, 62% to 81% of the felodipine doses were excreted in the urine and feces as metabolites. The rate of excretion by the kidneys had a biphasic pattern, with t1/2 values of 4 and 18 hours. Approximately 10% of the doses was excreted in the feces. PMID- 4017423 TI - Effects of age and disease on the pharmacokinetics and pharmacodynamics of sulindac. AB - The disposition and effect on hemostasis of a single 150 mg dose of sulindac was studied in young healthy subjects and in older patients with arthritis. Older patients were restudied after 2 weeks of sulindac, 150 mg b.i.d. The only difference in disposition of the first dose was a reduced plasma sulfone metabolite concentration in the elderly patients with arthritis. Chronic sulindac dosing resulted in accumulation of the drug and its sulfone and sulfide metabolites in plasma to a greater extent than previously reported for young subjects. No differences in renal clearance of sulindac and its sulfone metabolite related to age or chronic drug dosing were observed. No renal excretion of the active sulfide metabolite was detected. Bleeding time in the elderly patients was shorter than in the young healthy subjects before sulindac dosing, but was prolonged in the elderly patients after 2 weeks of dosing to values similar to control data from the young healthy subjects. This change correlated weakly with plasma sulfide metabolite concentrations. Differences in bleeding time were not reflected in changes in platelet aggregation induced by adenosine diphosphate either with respect to age or chronic drug dosing. Our data provide no justification for lowering the recommended dose of sulindac for patients older than 65 years of age. PMID- 4017424 TI - Lactate dehydrogenase isoenzymes in diabetic patients. AB - Lactate dehydrogenase (LDH) isoenzyme profiles in human platelets and the sera of patients with type I and II diabetes mellitus and vascular complications, as well as normal subjects were measured utilizing a recently established, modified micromethod. LDH-3 was the predominating species in platelets (37.5 +/- 3.0%), with LDH-2, 1, 4 and 5 following in decreasing order of concentration. The LDH 3/LDH-4 ratio in platelets varied from 6.2 to 1.38. Type I and type II diabetic patients with vascular complications showed a significantly higher ratio for LDH 3/LDH-4 (3.99 +/- 1.20 for DM I, 2.16 +/- 0.25 for DM II patients) than the mean ratio for normal subjects (1.14 +/- 0.08). This platelet-specific LDH isoenzyme pattern may be the result of frequent in vivo platelet-vessel wall interactions in the diabetic patients whose platelets are known to be hyperaggregable in in vitro test systems. Since non-diabetic patients patients with vascular complications also displayed a similarly elevated LDH-3/LDH-4 ratio, a wider classification is preferable, although the measurement of the LDH isoenzyme pattern will be helpful in assessing diabetic vascular complications. PMID- 4017425 TI - Influence of extrapancreatic digestive disorders on the indirect pancreatic function test with fluorescein dilaurate. AB - The detection rate of pancreatic disease using the indirect pancreatic function test with orally administered substrate fluorescein dilaurate (FDL) was evaluated in 290 patients. The sensitivity of the test was 84% in chronic pancreatitis (99 patients). Results were abnormal in all 5 patients with advanced pancreatic cancer and in 3 of 19 patients tested after a single episode of acute pancreatitis. The specificity of the FDL test was 89% when healthy subjects or patients with functional gastrointestinal disorders served as controls. However, it dropped to 62% when all patients with different organic gastrointestinal disorders were considered. This decrease could be attributed to patients with subtotal gastric resection and extensive small bowel disease, who were found to have the highest of pathological FDL test results, i.e., 70 and 35%, respectively. Not restricting the oral FDL test to the detection of primary pancreatic disease, in subtotal gastrectomy and extensive small bowel disease this test provides the opportunity to detect secondary pancreatic dysfunction. PMID- 4017426 TI - Comparison of radio-labeled DNA probe with a nonisotopic probe for assay of serum hepatitis B virus DNA. AB - A biotin-labeled DNA probe was compared to a 32P radio-labeled DNA probe for the detection of serum hepatitis B virus (HBV) DNA. Serum specimens were treated with proteolytic enzyme and detergent. DNA was extracted using phenol, denatured in sodium hydroxide and applied to a nitrocellulose filter paper using a vacuum filter device. The nitrocellulose filters were then incubated with either the biotin-labeled or the radio-labeled probe. Annealing of the probe, indicating the presence of HBV-DNA in the sample, was detected either by autoradiography for the 32P-labeled probe or by measuring the presence of an acid phosphatase attached to a streptavidin molecule for the biotin-labeled probe. Using the same 2-day time to complete the assays, excellent correlation of the qualitative and semiquantitative measurements were obtained using 20 HBsAg-positive and 9 HBsAg negative sera. The nonisotopic assay detected 1.0 pg of HBV-DNA, a sensitivity comparable to reported sensitivities of 32P-labeled HBV-DNA probes when similar assay times are used. 0.02 pg/microliter of HBV-DNA was detected in a normal serum to which HBV-DNA in a recombinant plasmid was added. Our results indicate that the biotin-labeled HBV-DNA probe is approximately as sensitive as the radio labeled probe for the detection of HBV-DNA using a similar assay time. Isotopic probe assays are more sensitive with longer assay times. The biotin-labeled probe offers the advantage of a longer shelf life and a nonisotopic assay procedure. PMID- 4017427 TI - Symposium on head and neck surgery. PMID- 4017428 TI - The viscerovertebral angle. The surgical avenue of the neck. AB - The viscerovertebral angle represents the evolution of thoughts assimilated from personal surgical experience and technique in the cervical area. It is a means whereby the surgeon may approach the operative challenge with ease, whether it involves singly or collectively the myovertebral pillar, the great neurovascular conduit, or the cervical visceral column from the level of the skull base well into the thorax to the innominate level. Thus, the surgeon is able to operate in a logical progression from the known to the unknown, comfortably and confidently in a predictable, reproducible manner. PMID- 4017429 TI - Surgery of the parotid gland and the viscerovertebral angle. AB - The use of consistent anatomic landmarks and the mobilization of the viscerovertebral angle facilitate localization of the facial nerve. This straightforward approach to surgery of the parotid gland provides a reproducible methodology for the preservation of the seventh cranial nerve. PMID- 4017430 TI - Endoscopic evaluation of the patient with head and neck cancer. AB - Endoscopic evaluation of the patient with head and neck cancer is important in the precise diagnosis and staging of the disease, as well as in ruling out synchronous disease. Various types of instruments and techniques may be employed in this evaluation. Endoscopic surgery for malignant disease may play a role in the treatment of selected lesions. PMID- 4017431 TI - Craniofacial approach to tumors of the head and neck. AB - The type of surgery described in this article is safe and effective when performed by an experienced team of plastic surgeons and neurosurgeons. In a very extensive series of patients with tumors of the cranial base, there has been only one surgical death. It occurred the day after surgery and was thought to have resulted from an error in administering anesthesia. Reconstruction is limited in patients with malignant disease, especially when the tumor is recurrent after radiation therapy. It is better to delay and not hide any area of potential recurrence. Reconstruction can be performed at 12 to 18 months. In nonmalignant tumors, total reconstruction is performed. Extensive surgery can be carried out with a good chance of cure. Initial rehabilitation is with a prosthesis, but later reconstruction will give an acceptable result. Thus, both surgeon and patient may embark on this hazardous course with a much greater degree of security and equanimity. PMID- 4017432 TI - Cancer surgery of the skull base. AB - Squamous-cell carcinomas are the most common type of malignant tumors arising in the region of the tonsils and palatine arch. This article describes surgical resection of such tumors with extension to the nasopharynx. The author's experience with over 40 patients confirms the safety of the procedure. PMID- 4017433 TI - Biogeometry. The logic in the process of selection, siting, design, construction, and transfer of flaps. AB - As knowledge of the basic sciences of anatomy and physiology increases and as clinical skills are enhanced by biotechnical advances, once-held perceptions of concepts and interpretations of principles are modified. The observation of these truths inspired this writing and will no doubt culminate at another time in a revision of biogeometry. PMID- 4017434 TI - Melanoma of the head and neck. AB - Cutaneous melanoma of the head and neck accounts for approximately 20 per cent of all melanomas. Variation in the incidence of melanoma by sex and by subsites within the head and neck is related to exposure to sunlight. Study of the precursor skin lesions of individuals and families at high risk for melanoma are providing new insights into the biology of melanoma. The clinical importance of such information is earlier diagnosis and treatment. With microstaging techniques it has become apparent that in many instances the primary tumor can be excised safely with narrower margins than were thought necessary in the past. The role of elective lymph-node dissection remains controversial, but when it is performed a complete dissection is recommended. Improvement in adjunctive methods of treatment is needed, but significant palliation can be achieved, with occasional long-term survival. PMID- 4017436 TI - [Indications for nuclear magnetic resonance tomography in tumors of the facial skeleton and neck area]. AB - The diagnostic value of magnetic resonance tomography is examined in relation to computed tomography on the basis of 32 patients subjected to magnetic resonance tomography who had pathological processes in the craniofacial, parapharyngeal and neck regions. The high power of contrast resolution, multiplanar imaging, and good circumscription of cervical vessels, offer advantages over computed tomography in respect of space-occupying growths in the median and lower parts of the craniofacial skull. A disadvantage is the poorer detectability of tumour conditioned bone destruction at the base of the skull and at the facial bones; in such cases, computed tomography remains the method of choice. PMID- 4017435 TI - Surgical management of recurrent or advanced squamous-cell cancer of the head and neck. AB - This article deals with the management of recurrent or advanced squamous-cell cancer of the head and neck and the surgical variations of management for cure and palliation. Patient reports are included in the discussion. PMID- 4017437 TI - [The craniocervical transitional area: a diagnostic problem]. AB - The case histories of six patients with spinal C1/C2 region lesions are presented. All cases were misinterpreted by clinical features and radiological findings over a long period. Radiological evaluation documents the significant improvement in diagnosis by supplementary use of computer assisted myelography. PMID- 4017438 TI - [Radiation exposure of the lens during CT of the orbital area]. AB - The exposure of the lens to irradiation in CT examination of the orbita was determined in a total of 80 patients via thermoluminescence dosimetry. Depending on a wide variety of parameters, exposures between 6.5 and 75 mGy were found with a mean of 28 mGy. By analysing the influence values thickness of layer and mAs product, suggestions for optimising orbita CT examinations are evolved. PMID- 4017439 TI - [ROC (receiver operating characteristic) study for the recognition of liver lesions on the computer tomogram]. AB - ROC examination was based on patient computer tomograms, in which lesions of the liver were simulated by image manipulation. The window width for optimal recognition of the lesions was found to be 128 Hounsfield units (HU). Evaluation of Receiver Operating Characteristics (ROC) by diameters and contrasts of the lesions yielded a contrast detail diagram largely reflecting conditions in clinical practice. The detectability--measured via the smallest visible diameter of the lesions--is inferior by the factor 3 to 60 to the results obtained with hole pattern phantoms. For example, in computer tomograms lesions of the liver of 24 mm and 4 HU or also 11 mm and 10 HU yield 70% true positive and 10% false positive findings. PMID- 4017440 TI - [Transhepatic course of the portal vein with a subcapsular branching]. AB - In a patient, investigated for uterine carcinoma, CT of the liver showed an anomalous course of a large portal vein, which traversed the liver and divided under the ventrolateral liver capsule in its branches. There were no signs of portal hypertension. PMID- 4017441 TI - [Normal findings and pathological changes of the patellar ligament in the computer tomogram]. AB - In the computer tomogram, the normal patellar ligament appears as a flat band with an average density of 110 HE. After trauma and also after chronic overloading, the cross-section increases, whereas the density decreases. CT is superior to conventional x-ray diagnosis and to sonography in respect of detecting and differentiating of circumscript changes in the patellar ligament. PMID- 4017442 TI - Applied potential tomography: possible clinical applications. AB - Applied potential tomography (APT) or electrical impedance imaging has received considerable attention during the past few years and some in vivo images have been produced. This paper reviews the current situation in terms of what in vivo results have been and are likely to be obtained in the near future. Both static and dynamic imaging are possible and these two areas are dealt with separately. Features of the existing in vivo imaging system are good tissue contrast, high speed data collection, good sensitivity to resistivity changes, low spatial resolution, low cost and no known hazard. It is concluded that the most promising way forward to clinical application in the short term is to use dynamic as opposed to static imaging. An example of lung imaging is shown and the application to measuring regional ventilation and pulmonary oedema is discussed. Use of APT for the detection of intraventricular bleeding in neonates is discussed as is the proven ability to study gastric physiology by imaging resistivity distribution changes following the ingestion of conducting or insulating fluids. Other areas of possible application which are considered are blood flow measurement, cell counting, measurement of lean-fat ratios and the detection of soft tissue lesions. PMID- 4017443 TI - Heart sound propagation in the human thorax. AB - Simultaneous quantitative recordings of pressure in the aorta near a prosthetic valve and at two locations externally on the chest provide data on certain aspects of sound propagation in the human thorax. On the basis of the different speeds of propagation, it is possible to distinguish between the longitudinal and transverse vibrations contributing to the external phonocardiographic signal. Digital signal processing was employed to derive transfer functions, correlations and power spectra. PMID- 4017444 TI - The effect of the transcutaneous electrode on the variability of dermal oxygen tension changes. AB - Transcutaneous oxygen measurements (TCPO2) are being used increasingly for the assessment of tissue viability in the ischaemic limb. The major objective with such a technique is to determine the critical level of TCPO2 which defines the boundary between skin viability and non-viability. To be able to do this, an assumption is made that measurements from different centres using various TCPO2 sensors are comparable. This study shows that static and dynamic changes of TCPO2 (air to oxygen breathing) made with two commercially available instruments are not directly comparable. We suggest that the physical characteristics of present TCPO2 electrodes are not optimal for measurements on adult skin. TCPO2 measurements made in conditions of skin ischaemia should be interpreted with caution because the ratio of local oxygen demand to blood flow is such that the measurement may be underestimated by TCPO2 electrodes with a high oxygen consumption. PMID- 4017445 TI - An inexpensive portable monitor for measuring evaporative water loss. AB - The measurement of evaporative water loss from the skin, using a ventilated chamber, usually requires two high-accuracy devices for the measurement of the inflow and outflow relative humidity. The water-loss rate is proportional to the difference between the inflow and outflow relative humidity, and a sensor with low absolute accuracy can be used if the same sensor measures both relative humidities. The system described uses an inexpensive sensor to measure the water loss rate with an accuracy of 10%. PMID- 4017446 TI - Effects of time-varying magnetic fields on fibroblast growth. AB - L929 mouse fibroblasts were exposed to sinusoidally varying magnetic fields. Compared with controls the exposed cells showed differences in morphology, clustering and orientation with respect to the magnetic fields and an increased mitotic rate. These effects are time dependent, but occurred at frequencies of 10 and 27 MHz. PMID- 4017447 TI - The influence of measurement precision on medical findings. AB - Medical researchers, epidemiologists and clinicians are all concerned with the observed incidence rates of various diseases and diagnostic findings. Such findings are necessarily based on imprecise procedures and instrumentation. The present study describes the theoretical extent to which the precision of instruments and procedures contributes to reported distribution curves and incidence rates of diagnostic findings. A numerical method is described for separating underlying distribution curves from the observed distribution curves which are distorted by measurement error. The method is illustrated by two examples: blood pressure measurements and QRS axis distributions in the ECG. PMID- 4017448 TI - [Treatment of ureteral colic with sodium diclofenac]. PMID- 4017449 TI - [Combined esophageal and gastric pH measurement in the study of gastroesophageal reflux disease]. PMID- 4017450 TI - [Clinico-therapeutic evaluation of the efficacy of lysozyme in the prevention and treatment of chronic recurrent bronchopulmonary disorders]. PMID- 4017451 TI - [The use of nifedipine in the treatment of hypertensive crises in patients with chronic uremia undergoing periodic hemodialysis]. PMID- 4017452 TI - [Piperacillin combined with gentamicin in the treatment of bacterial meningitis in children]. PMID- 4017453 TI - [The responsibility of the dental surgeon in anesthesia]. PMID- 4017454 TI - [A hypokalemic normotensive variant of the syndrome caused by nasal spray containing 9-alpha-fluoroprednisolone]. PMID- 4017455 TI - [Experience with immunosuppressive therapy of active chronic hepatitis using long term multiple corticoids]. PMID- 4017456 TI - [Evaluation of the clinical efficacy of fosfomycin lozenges in the prevention of complications in surgical interventions in odontostomatology]. PMID- 4017457 TI - [Double-blind evaluation of the antidyslipidemic effect of a combined phosphorylcholine and pantetheine product]. PMID- 4017458 TI - [Severe hypokalemic episode induced by abuse of fluoro-prednisolone acetate administered nasally and the simultaneous oral consumption of indapamide]. PMID- 4017459 TI - [Development of protected risk in pensionable disability in relation to new legislative reform]. PMID- 4017460 TI - [Syncope. Review of 510 cases]. PMID- 4017461 TI - [Clinical experimentation on the analgesic activity of zidometacin in odontostomatology]. PMID- 4017462 TI - [Double-blind trial on the trophic and anti-atherosclerotic preventive efficacy of a phosphorylcholine-pantetheine combination]. PMID- 4017463 TI - [Nifedipine drops in the treatment of hypertensive emergencies]. PMID- 4017464 TI - [Hemorrhoid syndrome in the aged. A particular pharmacotherapeutic approach]. PMID- 4017465 TI - [Toxicologic aspects of ethanol abuse]. PMID- 4017466 TI - [Effect of nifedipine on peripheral blood flow in patients with atherosclerotic arterial disease of the lower limbs. A controlled study]. PMID- 4017467 TI - [Clobetasone butyrate, a topical steroid in geriatrics]. PMID- 4017468 TI - [The significance of sulodexide in the prevention of obliterative atherosclerotic arterial disease of the lower limbs]. PMID- 4017469 TI - [Diacetylrhein in the treatment of degenerative arthropathies]. PMID- 4017470 TI - [Antihypertensive effect of long-term oral therapy with verapamil in elderly patients]. PMID- 4017471 TI - [Calcium antagonists in the therapy of cerebrovascular diseases]. PMID- 4017472 TI - [Atherosclerosis and diabetes]. PMID- 4017473 TI - [Frontobasal lesions with cerebrospinal fluid fistulae: neurosurgical treatment]. PMID- 4017474 TI - [Effects of atenolol and an atenolol-chlorthalidone combination on blood pressure values in hypertensive patients]. PMID- 4017475 TI - [Use of ciclonicate in the treatment of obliterative arteriopathies of the lower limbs]. PMID- 4017476 TI - [Alcoholism in the prison environment: a clinical approach]. PMID- 4017477 TI - [Hospital experiments with gentamicin administered by a simplified dosage schedule for children]. PMID- 4017478 TI - [Myocardial infarct in its acute phase. Recent therapeutic acquisitions]. PMID- 4017479 TI - [The so-called multiple leiomyomatous hamartoma of the lung]. PMID- 4017480 TI - [Cardiac decompensation. Notes on diagnosis and therapy]. PMID- 4017481 TI - [Measured nutrition in the aged]. PMID- 4017482 TI - [Behavior of several hormonal and nonhormonal parameters in obesity. 1. Blood prolactin]. PMID- 4017483 TI - [Evaluation of the use of oral cefatrizine in the treatment of acute bacterial infections of the respiratory tract]. PMID- 4017484 TI - [Mushroom poisoning. New diagnostic and therapeutic trends. Our experience]. PMID- 4017485 TI - [Hepatotoxicity of non-steroidal anti-inflammatory drugs]. PMID- 4017486 TI - [Intestinal ecosystem of children living in communities]. PMID- 4017487 TI - [Pathogenesis and evaluation of childhood hypoacusis]. PMID- 4017488 TI - [Maxillary localization of Ewing's sarcoma. Description of a case in a 5-year-old child]. PMID- 4017489 TI - [Sugar and dental caries]. PMID- 4017490 TI - [Therapy of arterial hypertension with a delayed-action clonidine and chlorthalidone combination]. PMID- 4017491 TI - [Clinical findings and test results in a group of patients with headaches treated with amitriptyline as compared with perphenazine]. PMID- 4017492 TI - [Efficacy and tolerance of dexindoprofen compared with diclofenac sodium in the treatment of osteoarthrosis patients]. PMID- 4017493 TI - [Current trends in the diagnosis and prevention of hypoacusis in children]. PMID- 4017494 TI - [Erythema nodosum in Giardia lamblia infestation]. PMID- 4017495 TI - [Contrast radiography: let's make it double-contrast]. PMID- 4017496 TI - [Chronic liver disease in rheumatoid arthritis: complication or association?]. PMID- 4017497 TI - [Behavior of several hormonal and nonhormonal parameters in obesity. II. Thyroid hormones (free T3, free T4, rT3)]. PMID- 4017499 TI - [Use of hypothalamic phospholipid liposomes in patients with irritable bowel syndrome]. PMID- 4017498 TI - [Effects of nadolol in hyperthyroidism]. PMID- 4017500 TI - [Fosfomycin: analysis of the antibiotic and its effects in odontostomatologic diseases]. PMID- 4017501 TI - [Behavior of several hormonal and nonhormonal parameters in obesity. 3. Lipid pattern and obesity]. PMID- 4017502 TI - [Noninvasive therapy of urinary lithiasis]. PMID- 4017503 TI - [Phoniatric and prosthetic treatment of hypoacusis in children]. PMID- 4017504 TI - [Possibilities and limits of microsurgery in patients with meningioma of the sellar region]. PMID- 4017505 TI - [Sinus arrest caused by clonidine during treatment of chronic opiate poisoning]. PMID- 4017506 TI - [Combination of thiazide diuretics and prostaglandins inhibitors in the treatment of nephrogenic diabetes insipidus]. PMID- 4017507 TI - [Behavior of various hormone and non-hormone parameters in obese subjects. IV. Obesity therapy]. PMID- 4017508 TI - [Josamycin in the treatment of infections of interest in childhood otorhinolaryngology]. PMID- 4017509 TI - [Drug therapy in auricular pathology]. PMID- 4017510 TI - [Sugar: a biologically pure and necessary energy source (from a conversation with Prof. Elio Polli. Interview by Francesco Tarentini Trojani]. PMID- 4017511 TI - Packaged commercial bacterial identification systems. AB - The authors attempt to provide a useful and current guide for clinical microbiologists who are seeking a review of the available packaged commercial systems for bacterial identification. Each system is outlined according to test principle, laboratory procedures, turn-around time, and limitations. Selected peer evaluations and references for many of the systems are also cited. PMID- 4017512 TI - Anaerobic identification systems. AB - Commercially produced prepackaged "kit" microsystems were evaluated for the identification of anaerobes. The API 20A and Minitek Anaerobe II systems by themselves were inadequate; even with the use of supplemental tests, agreement of identifications with a conventional method was only fair. AnIdent is a new and radically different system that provides accurate identifications after only 4 hours' incubation in room air without the need for a significant number of supplemental tests. PMID- 4017513 TI - The psychological status of overgenerated sentences. PMID- 4017514 TI - Levels of processing and vocabulary types: evidence from on-line comprehension in normals and agrammatics. PMID- 4017515 TI - Semantic restrictions on children's passives. PMID- 4017516 TI - The psychological relevance of transformational grammar: a reply to Stabler. PMID- 4017517 TI - "Gavagai!" or the future history of the animal language controversy. PMID- 4017518 TI - Headed records: a model for memory and its failures. PMID- 4017519 TI - The development of grammars underlying children's interpretation of complex sentences. PMID- 4017520 TI - People's knowledge about images. PMID- 4017521 TI - Metre and rhythm in piano playing. PMID- 4017522 TI - Rationality, memory and the search for counterexamples. PMID- 4017523 TI - Nasal polyps, bronchial asthma, and aspirin sensitivity: the Samter syndrome. PMID- 4017524 TI - The immunopathogenesis and clinical management of food hypersensitivity. PMID- 4017525 TI - Office diagnostic methods for allergic diseases. AB - The practice of allergy has been revolutionized in the past 20 years and has undergone a welcome transformation from an arcane art to an immunology-based clinical science. (It is hoped that the best features of the art will be retained, however.) An understanding of allergy diagnosis should provide the requisite information for the primary care physician to choose an allergy consultant wisely, and to understand the scientific basis of his methods and recommendations. PMID- 4017526 TI - Urticaria and angioedema: new insights and new entities. PMID- 4017527 TI - Weighting of populations for their mortality experience. PMID- 4017528 TI - A regional manpower plan for community medicine. PMID- 4017529 TI - Microcomputers and the work of a medical officer for environmental health at district. PMID- 4017530 TI - Towards readability and style. PMID- 4017531 TI - The symptomless salmonella excretor working in the food industry. PMID- 4017532 TI - An approach to health promotion in one region. PMID- 4017533 TI - Immunization as depicted by the British national press. PMID- 4017534 TI - Adverse reactions in adolescents to reinforcing doses of plain and adsorbed tetanus vaccines. PMID- 4017535 TI - Comparison of glycogen stores in 3- and 7-month-old lean and obese Zucker rats under fed and fasted conditions. AB - Glycogen content (mg/g) and stores (mg) were determined in 3- and 7-month-old obese and lean Zucker rats, under fed and fasted (48 hr) conditions. Hepatic content was higher in fed obese than in lean rats (3 months: 90 vs 70; 7 months: 107 vs 74); it was exhausted after fasting in lean but decreased by 56% in obese rats. Muscle content in fed obese and lean animals did not differ; it decreased comparably after fasting. Myocardial content was higher in fed obese than lean rats (3 months: 7.2 vs 3.6; 7 months: 7.5 vs 6.3); it was enhanced with fasting (10.0 vs 7.5). Total glycogen stores were higher in obese than in lean animals (3 months: 2500 vs 1400; 7 months: 4000 vs 2000) because of the hepatic store. The discussion includes a comparison with available data, taking into account methodological aspects, lipid stores and the FFA/carbohydrate interrelationship. PMID- 4017536 TI - Connective tissue metabolism in muscular dystrophy. Amino acid composition of native types I, III, IV and V collagen isolated from the gastrocnemius muscle of embryonic chickens with genetic muscular dystrophy. AB - The amino acid composition data on types I, III, IV and V collagen isolated from embryonic dystrophic skeletal muscle strongly indicate that alterations in collagen synthesis occur in intramuscular connective tissue of developing muscles in embryonic dystrophic chickens. The changes observed in the amino acid composition of dystrophic collagen were: (a) a selective removal of polar amino acids and substitution with non-polar amino acids; (b) significant decreases in basic (lysine, hydroxylysine and arginine) and hydroxylated (4-hydroxyproline and hydroxylysine) amino acids; and (c) significant increases in the amounts of glycine, proline and alanine. The amino acid substitutions suggest a genetic alteration in the collagen synthesizing process and a change in its structure. The variations in amino acid composition of collagen from dystrophic chickens could give rise to a decrease in both inter- and intramolecular cross-linking, thus decreasing the stability and functionality of newly formed collagen fibrils. The differences associated with the dystrophic collagen reported in this study are probably due to the differences in primary structure in terms of amino acid sequence rather than post-translational modifications. The structural differences noted would also lead to an alteration of the role collagen plays in regulating the differentiation of developing muscles. The changes in amino acid structure strongly suggest that the 'collagen' formed by dystrophic chickens should be considered a collagen-like protein or 'collagenoid'. PMID- 4017537 TI - Isolation and characterization of a homogeneous acid phosphatase from catfish liver. AB - A homogeneous, tartrate-inhibitable acid phosphatase (AcPase) was obtained from the liver of channel catfish (Ictalurus punctatus) by the use of Affi Gel-10 coupled aminohexyltartramic acid affinity chromatography. The enzyme has a molecular weight of 82,500 and is a dimer consisting of two apparently equivalent subunits with subunit weights of 35,000 +/- 3000. Amino acid composition data are presented and compared with those of mammalian acid phosphatases. Data suggest that the enzyme is a metalloacid phosphatase. Catfish liver AcPase exhibits two molecular forms with pI 5.66 and 5.37 which were separated by chromatofocusing. A spontaneous conversion of the less acidic form to a more acidic form was observed and this conversion was accompanied by a decreased sensitivity towards tartrate inhibition. PMID- 4017538 TI - Synthesis of heat shock proteins in quail red blood cells following brief, physiologically relevant increases in whole body temperature. AB - Cultured RBCs from quail respond to thermal stress (heat shock) by a rapid and dramatic change in gene expression. This change in gene expression includes the new and/or enhanced non-coordinate synthesis of a small group of heat shock polypeptides (HSPs) having molecular masses of 90,000, 70,000 and 26,000. RBCs obtained from hyperthermic quail exhibit a change in gene expression similar to that observed in RBCs heat-shocked in vitro. Since in vitro studies have linked the synthesis of HSPs in heat-stressed cells with thermotolerance, the similar change in gene expression in RBCs from hyperthermic quail suggests that, here too, this cellular response may be an important homeostatic mechanism by which avian RBCs cope with and/or survive hyperthermic conditions. PMID- 4017539 TI - Changes in the fatty acid composition of phospholipids from turbot (Scophthalmus maximus) in relation to dietary polyunsaturated fatty acid deficiencies. AB - Young turbot (1-20 g) were maintained for not less than 14 weeks on three diets: (1) a control diet containing normal amounts of polyunsaturated fatty acids (PUFA); (2) a diet totally deficient in PUFA; (3) a diet deficient in the (n-6) series of PUFA but containing (n-3) PUFA. At 14 weeks the fatty acid compositions of the phospholipids from liver, gut, gills and muscle were analysed. Large changes in the amounts of PUFA in the phospholipids were found. Fish maintained on the totally PUFA deficient diet 2 had retained arachidonic acid, 20:4(n-6), and docosahexaenoic acid, 22:6(n-3), at the expense of eicosapentaenoic acid, 20:5(n-3). Fish maintained on the (n-6) PUFA-deficient diet (3) contained decreased amounts of 20:4(n-6) and 22:6(n-3) while retaining 20:5(n-3). In all cases phosphatidylinositol had the lowest n-3/n-6 ratios. These results are discussed in terms of PUFA function. PMID- 4017540 TI - Bisalbuminemia in an amphibian. AB - Improved electrophoretic resolution revealed two albumin-like proteins in Taricha granulosa plasma (bisalbuminemia). The Taricha proteins were compared to mammalian, avian and reptilian serum albumins regarding molecular weight, amino acid composition, isoelectric character, solubility and the binding of hemin and dyes. The results indicate that although the two Taricha proteins have demonstrated hemoglobin-binding ability, they possess traits that characterize them to be true serum albumins. PMID- 4017541 TI - Isolation and characterization of nerve growth factor from Vipera lebetina (snake) venom. AB - Nerve growth factor from Vipera lebetina venom was purified by gel filtration and ion exchange chromatography steps. The NGF preparation obtained is a glycoprotein with weak arginine esterase activity. It hydrolyzes benzoylarginine ethyl ester (BAEE). Vipera lebetina NGF consists of multiple forms of protein with pI in the interval 9-10.5. All isoforms have identical molecular weights of 32,500. PMID- 4017542 TI - Electrophoretic analysis of soluble proteins and esterase, superoxide dismutase and acid phosphatase isoenzymes of members of the protozoan family trichomonadidae. AB - Polyacrylamide gel electrophoresis was used to compare the proteins and isoenzymes of esterase, superoxide dismutase, and acid phosphatase in soluble, whole-cell extracts of four strains of Trichomonas vaginalis, two strains of Trichomonas gallinae, and one strain each of Tritrichomonas foetus, Tritrichomonas augusta, Tetratrichomonas gallinarum, and Pentatrichomonas hominis. Intraspecific, interspecific, and intergeneric differences were found in protein and isoenzyme profiles. At least four to seven isoenzymes were detected among the ten strains for each of the three enzymes studied. Each strain usually contained one or two isoenzymes of both esterase and acid phosphatase, and two or three isoenzymes of superoxide dismutase. PMID- 4017543 TI - Analysis of lipids by gas-liquid chromatography and complementary methods in four strains of Aedes aegypti mosquitoes. AB - Fatty acid composition of total lipids, neutral lipids and phospholipids of strains of Aedes aegypti were determined. The fatty acid composition of the strains differed quantitatively with regard to the relative percentage of commonly occurring fatty acids. Gas-liquid chromatography of fatty acid methyl esters showed 18:1 (oleic or elaidic) to be the predominant fatty acid. The fatty acid was identified as oleic by argentation thin-layer chromatography. A modified colorimetric method was used to determine tissue-free fatty acids. The lipids were predominantly triacylglycerol with lesser amounts of free fatty acids and decreasing amount of sterol ester, sterol, monoacylglycerol, diacylglycerol and hydrocarbons. The data show considerable lipid differences between the Caribbean strains (Les Cayes, Haiti, and San Juan, Puerto Rico) and the Jakarta (Indonesia) strain. The Shimba Hills (Kenya) strain was more similar to Jakarta than to the Caribbean strains. The results obtained with the different strains are discussed in relation to the established oral susceptibility to Dengue 1 and Dengue 2, yellow fever, and genetic analysis by isoenzyme studies. PMID- 4017544 TI - Schistosoma haematobium: neutral lipid composition and release by adults maintained in vitro. AB - Thin-layer chromatographic analyses showed that the major neutral lipid fractions of whole-worm extracts of male and female adult Schistosoma haematobium were free sterols, triacylglycerols and sterol esters. Worm-free incubates of adult worm pairs contained free sterols only. The major fractions of worm-free incubates from separated worms were free fatty acids and free sterols; traces of triacylglycerols and sterol esters were also detected. Females incubated in a group of ten released more free fatty acids than ten incubated singly. Males incubated singly released more free sterols than a similar number incubated in a group. Females released more free sterols than males. PMID- 4017545 TI - Synthesis of chain elongated-desaturated fatty acids from palmitic acid by liver and brain microsomes during the development of the pig. AB - Rates of chain elongation-desaturation of C16:0 were compared for liver and brain microsomes in fetal, neonatal and postnatal piglets. Rates of chain elongation of C16:0 were greatest in liver in the postnatal period. For all developmental periods examined, the amount of chain elongated fatty acid of C20 or greater chain length exceeded the amount of C18 precursors synthesized from C16:0. These observations suggest that chain elongation of fatty acids occurs during the latter part of gestation at rates equivalent to that observed in the early postnatal period. PMID- 4017546 TI - In vitro 16 alpha-hydroxylation of progesterone by testes of crab-eating monkey (Macaca irus): a characteristic of primates? AB - Radioactive 16 alpha-hydroxyprogesterone was obtained as one of the major metabolites of [14C]pregnenolone and progesterone by testicular homogenates of an adult crab-eating monkey (Macaca irus). 16 alpha-hydroxylation of progesterone occurred by incubation of testes of men and and the monkey, but not by those of rodents and other vertebrates examined. PMID- 4017547 TI - A comparison of the effects of duodenal glucose infusion on carbohydrate and lipid metabolism in liver, adipose tissue and small intestinal mucosa in sheep. AB - The effects of duodenal glucose infusion on the specific activities of some enzymes of carbohydrate and lipid metabolism in the liver, perinephric adipose tissue and small intestinal mucosa of sheep were examined. Lipogenic enzyme activity was generally greatest in adipose tissue and lowest in liver and the response of these enzymes to glucose infusion was similarly greatest in adipose tissue. Glycolytic enzyme activity was significantly increased in all three tissues following duodenal glucose infusion. The effects of increasing carbohydrate availability in the small intestine in relation to tissue metabolism in sheep are discussed. PMID- 4017548 TI - Plasma vitellogenin in landlocked Atlantic salmon (Salmo salar Ouananiche): isolation, homologous radioimmunoassay and immunological cross-reactivity with vitellogenin from other teleosts. AB - Vitellogenin was isolated by affinity chromatography and gel filtration from landlocked Atlantic salmon plasma. Vitellogenin was labelled with iodine-131 using iodogen and an homologous radioimmunoassay was developed. There was poor immunological cross-reactivity with vitellogenin or plasma from other teleosts. Parallelism of the vitellogenin standard to the displacement by plasma of vitellogenic salmon allowed the assay to be used to evaluate the seasonal concentration profile of vitellogenin in female adult salmon. Extracts of liver or ovary from female Atlantic salmon also yielded displacements parallel to the vitellogenin standard in the assay. PMID- 4017549 TI - DNA homologies between the rainbow trout, chum salmon and coho salmon. AB - The thermal stabilities of hybrid duplexes between the DNAs from three salmonid fish species were monitored as measures of DNA homology. The chum salmon, Oncorhynchus keta, and coho salmon, Oncorhynchus kisutch, had more DNA homology with each other than either had with the rainbow trout, Salmo gairdnerii. Morphological, ecological and protein similarities between the coho salmon and the rainbow trout may be due to parallel or convergent evolution. PMID- 4017550 TI - Metabolism of radiolabelled chylomicron lipids in intact and hepatectomized rats. AB - Intact rats removed more radiolabelled triacylglycerol, cholesterol, and cholesterol ester but not phosphatidylcholine (PC) in the first 6 min than hepatectomized rats. There was no difference between intact and hepatectomized rats in the transfer of radiolabelled chylomicron lipids to other lipoproteins. Specific radioactivity measurements demonstrated a net transfer of PC (intact and hepatectomized rats) and unesterified cholesterol (intact rats only) onto both the low density lipoprotein/high density lipoprotein-1 (LDL/HDL1) and HDL2 fractions. [3H]Fatty acids were rapidly incorporated into blood cell phospholipids and into HDL and LDL cholesterol esters of both intact and hepatectomized rats. Substantial rearrangements of [3H]palmitate occurred during lipid uptake by liver. PMID- 4017551 TI - A survey of polar and nonpolar lipids extracted from snake skin. AB - The cast skins of 24 species of snake (four families) were extracted with chloroform:methanol and the lipids recovered (4.2-14.0% of dry weight of shed epidermis) were analyzed by thin layer chromatography (TLC). Skins from all species had large amounts of cholesterol and free fatty acids and most had one or more lipids with TLC mobility similar to triglycerides. Many had a lipid with mobility similar to cholesterol esters. Polar lipids showed much less variation in composition. All species showed large amounts of phospholipids (sphingomyelin, phosphatidylcholine, and phosphatidylethanolamine). All skins contained glycolipids with mobilities similar to monohexosylceramides as well as a number of lipids with mobilities similar to those of ceramides but giving glycolipid like color reactions when heated with sulfuric acid. PMID- 4017552 TI - Comparative analyses of aortic type IV collagen in various species. AB - Aortic type IV collagen from several species contained identical patterns of high molecular-weight aggregates as determined by HPLC. Slab gel electrophoresis in one and two dimensions revealed a similar chain composition in these collagen samples. The basic structural components were similar in size to the long form of 7-S collagen. These studies suggest that a common supramolecular assembly of type IV chains exist within aortic basement membrane matrices. PMID- 4017554 TI - Effects of anti-albumin sera on the synthesis and secretion of soluble proteins by monolayers of hepatocytes. AB - Hepatocytes were isolated from male Sprague-Dawley rats and monolayer cultures prepared. The effects of supplementation of the incubation medium with homologous and heterologous antisera directed against albumin on the synthesis and secretion of soluble proteins were ascertained. Supplementation of the medium with antisera generally resulted in a time related decrease in the synthesis and secretion of soluble proteins. The observed inhibition did not appear to be due to deficient amino acid uptake and the cell membranes remained intact in the presence of antisera. The results are discussed in relation to findings obtained with malignant cells. PMID- 4017553 TI - Brown adipose tissue from fetal rhesus monkey (Macaca mulatta): morphological and biochemical aspects. AB - Brown adipose tissue (BAT) from fetal rhesus monkeys microscopically resembled adult rodent BAT containing multiocular fat cells with numerous mitochondria. Mitochondrial carnitine palmitoyl transferase activity was lower than that in adult rodents and adenine nucleotide translocase activity was similar to that reported for rats. Rhesus monkey BAT mitochondria (BATM) possess an uncoupling protein that is characteristic of BAT as evidenced by the binding of [3H]GDP, the inhibition by GDP of the high Cl- permeability or rapid alpha-glycerol-3 phosphate oxidation. Electrophoretic analysis of BATM showed the presence of a 32,000 mol.wt protein which was enriched by procedures established for the isolation of BATM uncoupling protein. PMID- 4017555 TI - The isolation and characterization of lysozyme from human foetal membranes: a comparison with the enzyme from other sources. AB - Lysozyme (muramidase) was isolated from an acidic extract of human foetal membranes by adsorption and elution from octadecyl silica. It was further purified by gel-filtration and ion-exchange. The final product was homogeneous by high performance liquid chromatography (h.p.l.c.) and electrophoresis. It was indistinguishable from human milk lysozyme by all criteria investigated, including amino acid composition, electrophoretic mobility, retention time on h.p.l.c. and sequence of the first nine residues. Human uterine decidual tissue was shown to contain a similar concentration of lysozyme to foetal membranes. The enzyme was also present at lower concentrations in amnion, placenta and amniotic fluid. PMID- 4017556 TI - Using a microcomputer and video camera to simultaneously track 25 animals. AB - A system that can simultaneously track about 25 animals with the position of each determined once a second is described. The system includes a 6809 microprocessor, OS-9 operating system and application programs written in assembly and BASICO9. The movements and changes in direction of the subjects can be determined and displayed in real time. The system has proven to be valuable in studying the chemotaxis of nematodes and should be applicable to the study of other animals that can be viewed with high contrast. PMID- 4017557 TI - A time-lapse, image digitization videomicroscope system based on a mini computer with large peripheral memory. AB - We describe a time-lapse image digitization videomicroscope system that uses a mini computer as the main processing unit in conjunction with a large peripheral memory for storing multiple digitized images. The advantage of the system lies in its ability to facilitate acquisition and analysis of data relative to size, location and optical density of cells and cellular structure using elementary image processing techniques. This system can also potentially control microscope stage movement, enabling acquisition of larger amounts of data per time-lapse experiment. PMID- 4017558 TI - Computer-aided rhinometry: analysis of inspiratory and expiratory nasal pressure flow curves in subjects with rhinitis. AB - Airflow through the nose was measured by posterior rhinometry with the aid of a microcomputer to study reproducibility of pressure-flow curves, the ease of detection of nasal congestion and decongestion, and mathematical modelling of P-V curves. In twelve subjects with rhinitis, the median coefficient of variation of nasal airway resistance was between 4.9% and 14.4% and was not significantly affected by inspiration and expiration, congestion and decongestion, or the flow rate at which it was measured. Fitting of 630 P-V curves to a quadratic equation was usually excellent, particularly during expiration. PMID- 4017559 TI - On line determination of airway resistance by plethysmography and microcomputer. AB - On line determination of airway resistance is carried out by an Apple II connected to a flow body plethysmograph. Recognition of the panting maneuver is performed in real time. Linear drift of plethysmographic volume V is eliminated by taking the derivatives V and Vm of V and mouth flow Vm. Linear regression of V on Vm yields an estimate R of airway resistance, at a volume close to functional residual capacity FRC. The values of FRC is given by linear regression of V on Pm, the derivative of mouth pressure. No significant difference has been found between the estimates of the specific conductance sG calculated by linear regression and by spectral analysis of V and Vm. As variability of sG can be kept below 10%, the regression technique appears to be reliable for routine patient testing and pharmacological studies. PMID- 4017560 TI - Intellectual functioning and abstraction ability in major affective disorders. PMID- 4017561 TI - Diagnosis of manic depressive illness in blacks. PMID- 4017562 TI - Torque response in psychotics and normal controls: a study in an Asian culture. PMID- 4017563 TI - Clinical implications of Axis I-Axis II interactions. PMID- 4017564 TI - Circadian rhythm in primary affective disorder. PMID- 4017565 TI - Factors influencing the occurrence of hand eczema in adults with a history of atopic dermatitis in childhood. AB - A series of 955 persons aged 24-44 years, with atopic dermatitis in childhood, were interviewed in order to identify factors which increase the risk of developing hand eczema in adult life, or aggravate already existing hand eczema. Endogenous (constitutional) factors were in general of greater importance than exogenous factors, viz. chemicals, water, soil and wear (friction). Eczematous involvement of the hands in childhood was of predominant importance. In individuals without such involvement, severe (widespread) dermatitis in childhood was a dominant factor. Other factors, each of them significantly more important than the exogenous ones, were persistent eczema on other parts of the body and dry/itchy skin. The factors female sex, family history of atopic dermatitis and simultaneous bronchial asthma/allergic rhinitis were associated with increased risk of developing hand eczema in adult life, but were of limited importance compared with the other endogenous and the exogenous factors. PMID- 4017566 TI - Clonidine: irritant and allergic contact dermatitis assays. AB - Clonidine in petrolatum, clonidine transdermal device, and its placebo device were assayed for relative irritancy potential (21-day cumulative irritancy assay) and allergic contact dermatitis potential (Draize repeat insult patch test assay). Both clonidine in petrolatum and the clonidine transdermal device appear to be of minimal irritancy potential. Only the clonidine device demonstrated, in the Draize assay (and in clinical trials), allergic contact dermatitis potential. Its relatively delayed onset of demonstration of allergic contact sensitization in clinical trials requires investigation as to mechanism. PMID- 4017567 TI - Identification of psoralen, 8-methoxypsoralen, isopimpinellin, and 5,7 dimethoxycoumarin in Pelea anisata H. Mann. AB - 5,7-dimethoxycoumarin and isopimpinellin, together with the well-known phototoxic, photo-irritant furanocoumarins psoralen and 8-methoxypsoralen, were isolated and identified from leaves and fruits of Pelea anisata H. Mann, a plant whose fruit are used in the construction of mohikana leis used in parts of the Hawaiian Islands. The presence of phototoxic furanocoumarins would explain the occurrence of photodermatitis in the wearers of the leis. PMID- 4017568 TI - Aluminium in Finn chambers reacts with cobalt and nickel salts in patch test materials. AB - Aluminium has a greater affinity for electrons than cobalt and nickel. Therefore, cobalt and nickel ions would be expected to exchange with metallic aluminium in Finn chambers. This theory has been proven to be valid, as shown in 2 series of experiments: first, cobalt and nickel salt solutions (0.25 M) etch a metallic aluminium surface; secondly, aluminium Finn chambers kept in 10(-3) M nickel salt solutions significantly reduce the concentration of dissolved nickel. Dichromate solutions do not etch an aluminium metal surface significantly. Petrolatum, which is routinely used as vehicle in standard patch tests, probably protects the aluminium of Finn chambers from the interaction of cobalt and nickel salts. The interaction may have significance in tests with solutions. PMID- 4017569 TI - Sensitizing potential of 2-hydroxyethylmethacrylate. AB - Guinea pigs exhibited none or slight responses to sensitization with low concentrations of 2-hydroxyethylmethacrylate in the guinea pig maximization test, while 60-100% reacted to high concentrations regardless of the vehicle used for induction. Petrolatum, water, soybean oil and a mixture of oil and 2-butanone (sbomek) were used as vehicles for elicitation. The neat methacrylate was less effective than dilutions in any vehicle, petrolatum being the best. The major determinant of the frequency of response was the concentration used for intradermal induction. An increase in frequency and in duration of responsiveness after treatment with cyclophosphamide 3 days before challenge suggests that hydroxyethylmethacrylate preferentially stimulates the suppressor cell function. PMID- 4017570 TI - Facial dermatitis from epoxy resin in a helmet. PMID- 4017571 TI - Allergenic degradation products of para-tertiary butylphenolformaldehyde plastic. PMID- 4017572 TI - Is cobalt naphthenate an allergen? PMID- 4017573 TI - Propolis contact dermatitis. PMID- 4017574 TI - Photodermatitis from musk ambrette in barbers' cologne. PMID- 4017575 TI - Tego dermatitis. PMID- 4017576 TI - Phytophotodermatitis induced by Ruta chalepensis L. PMID- 4017577 TI - Contact urticaria from papain in a soft lens solution. PMID- 4017578 TI - Nickel sensitivity as a complication of squaric acid dibutylester treatment of alopecia areata. PMID- 4017579 TI - Contact dermatitis from novocaine in Gerovital cream. PMID- 4017580 TI - Allergic contact dermatitis to cashew nut. PMID- 4017581 TI - Contact allergy to unsaturated polyester in a boat builder. PMID- 4017582 TI - Primary mesenteric venous thrombosis with recurrence. PMID- 4017583 TI - Methyl methacrylate cement induced pseudoaneurysm of the right common femoral artery. PMID- 4017584 TI - Consensus development summaries. Lowering blood cholesterol to prevent heart disease. National Institutes of Health. PMID- 4017585 TI - DNR procedures: purple dots revisited. Grand Jury of the Supreme Court of the State of New York, Queens County. PMID- 4017586 TI - Drunken injured drivers: are they "getting away with murder"? PMID- 4017587 TI - Effects of competition in medicine: practice characteristics of physicians in proprietary and nonproprietary hospitals. AMA Council on Medical Service. PMID- 4017588 TI - Reflections on medicine. What policy? PMID- 4017589 TI - Alcohol, law and public policy: current controversies. PMID- 4017590 TI - Isolation of Mycoplasma bovis from bulk milk. AB - The prevalence of mycoplasma in Vermont dairy farms was determined by two surveys conducted in March 1983 and January 1984. Bulk tank milk samples representing 74% and 62% of the herds respectively were cultured. Mycoplasma bovis was detected in 3 of the 2,346 bulk samples collected in the initial survey. The infection rate was 1.3 herds per thousand (95% confidence interval: 0.6-2.0 herds per thousand). No positive cultures were obtained in the second survey. PMID- 4017591 TI - Presumptive organophosphate-induced delayed neurotoxicity in a paralyzed bull. AB - A case of presumptive organophosphate-induced delayed neurotoxicity in a bull is described. All signs were referable to a focal cervical or diffuse spinal cord lesion. These included recumbency with severe symmetrical paresis of all 4 limbs, the hind limb involvement being greater than the forelimbs. CSF analysis was normal. The bull was killed and necropsied. There were no gross CNS lesions. Histopathologic finds are characterized and their resemblance to lesions observed in delayed neurotoxicity caused by organophosphate compounds is discussed. The bull had been treated with organophosphate insecticide (famphur) 43 days prior to the onset of signs. PMID- 4017592 TI - The mammalian rete ovarii: a literature review. AB - The rete ovarii is the homologue of the rete testis. It develops from cells of mesonephric origin which immigrate into the developing gonad of the embryo. The mature form of the rete ovarii is generally found to be groups of anastomosing tubules lined by cuboidal or columnar epithelium. These tubules are usually located in the hilus of the ovary, but may extend through the medulla or be isolated in the mesovarium adjacent to the hilus. The rete is often continuous with the transverse ductules through which it contacts the longitudinal duct of the epoophoron. The rete ovarii is important in the control of meiosis in the maturing ovary. Cells of the rete ovarii differentiate to form granulosa cells as well. The rete is also credited with secretory capability, a hypothesis supported by the observation of secretory material in the lumina of the rete tubules in several species. Cysts have been observed in the rete ovarii of several species. The rete ovarii of the adult does not appear to be a functionless vestige as has been previously reported. PMID- 4017593 TI - The use of milk progesterone and electronic vaginal probes as aids in large dairy herd reproductive management. AB - In a large herd 427 cows were examined for reproductive condition 26 to 34 days after calving. Progesterone profiles were obtained from a total of over 5000 milk samples which were taken twice weekly for 4 weeks, starting at the time of examination, and again 21, 23, and 25 days later. Researchers lived on the farm during the experiment to sample cows and record all data. Electronic probe measurements of cervical-vaginal mucus also were obtained. All cows were inseminated artificially with frozen semen from one organization. Eleven percent of the cows were not inseminated in the estrual phase as determined by substantial concentrations of progesterone in milk (MP), and 2% were pregnant and aborted following insemination. The MP 23 to 25 days after insemination essentially was 100% accurate in predicting nonpregnancy and was preferable to day 21. When used in conjunction with MP on the day of insemination pregnancy prediction 23 to 25 days after insemination was 84% accurate. Non-return rate 60 days after insemination was 7% higher than palpated pregnancy rate. The use of electronic probes under large herd conditions was labor intensive and did not give repeatably distinctive values at estrus. PMID- 4017594 TI - Outcome of respiratory intensive care for the elderly. AB - We followed 1018 patients admitted consecutively to a multidisciplinary respiratory ICU (RICU), with special attention to patients aged 75 yr and over. The elderly had a higher RICU (11/49) and in-hospital (21/49) mortality than younger patients. The 28 survivors of hospitalization had a lower acute physiology score (APS) than nonsurvivors on admission (16.1 +/- 7.8 vs. 21.8 +/- 8.9, respectively), indicating less severe illness. The quality of long-term survival (12 to 24 months) was assessed using an open-ended questionnaire. Eighteen hospital survivors were alive at the time of follow-up and the quality of life was deemed satisfactory by 10 of 13 patients who were living independently. Only two of 28 survivors had been transferred to nursing home care, and two were in acute care hospitals. We conclude most elderly patients discharged from the RICU consider their lifestyle satisfactory and are not a large drain on community health care resources. Further studies of the screening process which determines RICU admission are necessary, because unimodal criteria such as age and APS after admission were not of prognostic value. PMID- 4017595 TI - Lung mechanical profiles in acute respiratory failure: diagnostic and prognostic value of compliance at different tidal volumes. AB - The mean airway pressure difference within a respiratory cycle at end-inspiration was measured at different tidal volumes (VT) in 59 patients treated with mechanical ventilation, and plotted in a pressure-volume (P-V) diagram. Regression analysis revealed three types of regression lines which were clearly correlated with clinical pulmonary condition and outcome. The slope of such regression lines may be a more realistic representation of lung elasticity than conventional total static compliance, which is measured at only one VT, and the intercept of these lines may be a more appropriate reflection of operating lung volume than functional residual capacity. Ventilator settings should put the patient's lungs on the steepest part of the P-V curve with the smallest intercept, while maintaining acceptable arterial blood gas tensions. PMID- 4017596 TI - Inotropic effect of different albumin solutions on isolated papillary muscle. AB - We used a papillary muscle assay to study the inotropic effect of albumin solution. Unlike specially prepared citrate-free solutions, commercial preparations produced a negative inotropic effect. This is because their high citrate concentrations bound much of the calcium, so that little ionized calcium was available for physiologic processes. Citrate-free albumin did not show any inotropic effect on isolated papillary muscle. The amount of albumin normally used for resuscitation should not have enough citrate to depress ionized plasma calcium. Our experiments showed no evidence for primary myocardial depressant action of a commercial albumin preparation. PMID- 4017598 TI - A simple method for estimating compliance. AB - In intensive care medicine, pulmonary compliance is one of the very helpful diagnostic indices. Because of technical difficulties, however, the measurement of pulmonary compliance is often reduced to a rough guess of the compliance of the total respiratory system. The technical problems can be overcome using a computer to solve the basic equations with the least-squares fit (LSF) method. Unfortunately, this method requires such a long calculation time that bedside breath-by-breath calculations are impracticable on small computers. A simple computer algorithm (mean-values method) was therefore developed and compared to the LSF method. Compliance values calculated by either procedure were practically identical in ventilated patients. However, by reducing computing time to 30% of the LSF method, our mean-values algorithm enabled real-time estimation of compliance breath-by-breath. PMID- 4017597 TI - Complications after overdose with tricyclic antidepressants. AB - We reviewed 72 consecutive cases of tricyclic antidepressant (TCA) overdose (OD) admitted from the emergency ward (EW) to the ICU between 1977 and 1982. Most patients were seriously ill before ICU admission: 70% were comatose; 68% were intubated, including 61% in need of mechanical ventilation; and 30% were hypothermic. One patient died after ICU admission. ECG abnormalities were present in 37 (51%) patients in the EW. These abnormalities were associated with higher TCA plasma levels, but not with either acidosis or hypoxemia. Of 14 patients without ECG abnormalities or the need for intubation in the EW, none developed new ECG abnormalities or required ventilatory support. No patient had a late complication after transfer from the ICU, after a mean stay of 2.1 days. Late, unexpected complications in TCA OD are very rare. Our study suggests that TCA OD patients who do not have an abnormal ECG and do not require ventilatory support at the time of initial evaluation may not need ICU admission simply for intensive observation. PMID- 4017599 TI - Limitations of thermodilution ejection fraction: degradation of frequency response by catheter mounting of fast-response thermistors. AB - The present study examined whether catheter-mounting of a fast-response thermistor impaired the thermistor's ability to measure rapid temperature changes during thermodilution measurement of ejection fraction (EF). The response to a square-wave temperature change of six fast-response thermistors mounted on commercially available, pulmonary artery balloon-flotation catheters was compared to the response of a similar but unmounted fast-response thermistor. The response of the catheter-mounted fast-response thermistors recorded only 82% to 92% of a step-temperature change at 0.5 sec, and 88% to 96% of the step change at 1.0 sec. In contrast, the unmounted fast-response thermistor responded to 100% of the step change in 125 msec. The response of the catheter-mounted fast-response thermistors demonstrated an important slow component (second time constant) introduced by the catheter body, so that equilibration to a temperature change was not complete for about 6 sec. This slow equilibration lowered EF measured by thermodilution below true EF. PMID- 4017600 TI - Changes in conjunctival oxygen tension and temperature with advancing age. AB - The conjunctival oxygen monitor reflects oxygen tension of the internal carotid artery without introducing the heating artifact characteristic of transcutaneous monitors. It is now being used in the ICU and the operating room to measure accurately and continuously Po2 and temperature of conjunctival tissue. We examined the effect of aging on these values in 101 healthy adult subjects. Mean conjunctival oxygen tension (58 +/- 14 torr) and temperature (34.9 +/- 0.6 degrees C) decreased significantly (p less than .01) with advancing age. Monitoring the conjunctival capillaries may prove to be a useful adjunct to patient care, but the effect of aging must be considered in any such measurement. PMID- 4017601 TI - Acute intracranial hypertension during amiodarone infusion. PMID- 4017602 TI - Superior vena cava syndrome and pulmonary artery catheterization. PMID- 4017603 TI - Decisions on prolonging life. PMID- 4017604 TI - Changes in pulmonary blood flow during wedge pressure measurement in a neonate. PMID- 4017605 TI - Dithiocarbamate intoxication: a serious entity? PMID- 4017606 TI - Catheter measurement of mixed venous oxygen saturation. PMID- 4017607 TI - Hypoxemia, cellular hypoxia, and the oxyhemoglobin dissociation curve. PMID- 4017608 TI - Intravenous vs. nebulized salbutamol for treatment of severe status asthmaticus. PMID- 4017609 TI - Primary mediastinal echinococcosis. AB - Computed tomography findings with surgical details are presented in a case of hydatid cyst of posterior mediastinum, a rare site of involvement in echinococcosis infestation. The computed tomography appearance of posterior mediastinal echinococcosis is quite characteristic and can be readily distinguished from other cystic lesions of the mediastinum. Computed tomography provides additional information regarding the involvement of neighboring structures. In this case, computed tomography detected involvement of the descending aorta. PMID- 4017610 TI - Atypical computed tomography findings in a case of orbital pseudotumor. AB - The computer tomographic manifestations of orbital pseudotumors are varied. Among these findings, tram-tracking of the optic nerve sheath complex is rare. A patient with this unusual scan appearance is presented. Despite rapid clinical response to steroid therapy, this patient showed little initial improvement on computed tomography. The use of computed tomography scanning in the management of orbital pseudotumor is discussed. PMID- 4017611 TI - An unusual computed tomography appearance of nasopharyngeal carcinoma: a case report. AB - The computed tomography findings of an unusual case of nasopharyngeal carcinoma are presented. Typical features of nasopharyngeal carcinoma from clinical, pathologic, and radiologic aspects are discussed. Atypical features of this case are presented, consisting of extensive muscular infiltration and lack of destruction of contiguous bony structures. PMID- 4017613 TI - Computed tomography of mediastinal cystic hygroma in an adult: case report and review of the literature. AB - Conventional and computed tomography findings in a cystic hygroma (lymphangioma) of the middle mediastinum in an adult are reported and compared with previously reported cases. The pertinent literature is reviewed. PMID- 4017612 TI - Total internal carotid artery occlusion by a benign carotid body tumor: a rare occurrence. AB - A rare case of a carotid body tumor that completely occluded the internal carotid artery is presented. To our knowledge this is only the second such case documented by angiography. In the present computed tomography era, the role of vascular imaging in these tumors is discussed and the varied clinical presentations of these neoplasms are reviewed. The confusion between the locally malignant behavior of some of these lesions and the accepted definition of a malignant carotid body tumor is discussed. PMID- 4017614 TI - Evaluation of traumatic rupture of descending aorta by aortography and computed tomography: case report with follow-up. AB - Small aortic injuries are difficult to detect by computed tomography. We report a patient with a traumatic aortic injury that was not demonstrated on two high resolution computed tomography scans 1 month apart despite prior angiographic demonstration of the lesion. PMID- 4017615 TI - Computed tomography of xanthogranulomatous pyelonephritis. AB - The computed tomography findings in two cases of xanthogranulomatous pyelonephritis are presented. There was diffuse involvement of the kidney in one case, with correlation with the pathologic specimen and microscopic findings. In the second case there was focal involvement of the kidney. Computed tomography greatly assisted in making a correct preoperative diagnosis and in assessing the degree of extrarenal involvement. PMID- 4017616 TI - Primary mediastinal hemangiopericytoma: computed tomography correlation. AB - A case of primary mediastinal hemangiopericytoma with computed tomography correlation is presented. Although this is rare cause of mediastinal mass, the diagnosis should be considered when computed tomography of the mass shows contrast medium enhancement, particularly if there is a curvilinear encircling structure suggesting a large feeder vessel. PMID- 4017617 TI - Computed tomography of osteoid osteoma. AB - Computed tomography revealed a radiolucent nidus with a surrounding zone of osteosclerosis in 17 patients with osteoid osteoma. Plain films did not reveal any abnormality in 5 patients. Conventional tomography was negative in 3 patients. Computed tomography is the modality of choice for detection of osteoid osteoma when the lesion is deep-seated or when it occurs in complex anatomic regions with curvilinear and overlapping surfaces, such as acetabulum, knee, and spine. PMID- 4017619 TI - Ho'oponopono, "to make right": Hawaiian conflict resolution and metaphor in the construction of a family therapy. AB - It has been noted in the literature that community conflict resolution rituals have many structural and functional similarities to the goals and methods of psychotherapy. A Hawaiian form of conflict resolution called ho'oponopono ("to make right, orderly, correct") is a case where a conflict resolution format actually was used to create a culturally appropriate family therapy. This was done under the sponsorship of a Hawaiian social welfare organization with Hawaiian ancestry therapists. An important element in the transformation and usefulness of ho'oponopono as a Hawaiian therapy is the maintenance and incorporation of metaphoric understandings about the nature and dynamics of Hawaiian social relations. PMID- 4017620 TI - Comparative studies of normal and genetically hyperplastic lens epithelia II: lectin-induced cell agglutination and 125I-lectin uptake by cells. AB - The reactions of lectins with dissociated and cultured epithelial cells from hyperplastic lenses of two unrelated chick strains, Hy-1 and Hy-2, characterised by hyperplasia of the lens epithelium, and lenses of a normal genotype (N) were investigated using four different lectins. Three methods of monitoring lectin binding to cell surfaces were employed. Each of the four lectins used showed an individual pattern of reactivity to separated membrane components. Data obtained with the three labelling methods showed the same trend viz: increased agglutinability and high affinity for binding of all four lectins by Hy-1 and Hy 2 cells. These results suggest that Hy-1 and Hy-2 lens epithelial cells are characterised by alteration in their cell surfaces. PMID- 4017621 TI - The photosensitized oxidation of the calf lens main intrinsic protein (MP26) with hematoporphyrin. AB - Hematoporphyrin (HP), a drug used for the treatment of tumors including intraocular tumors, is an efficient photosensitizer. In addition to its therapeutic value, it also produces a phototoxic side effect in the skin. To test whether such effects may also occur in the eye, calf lens fiber membranes were photolyzed in the presence and absence of 1 mM HP. A marked increase (ca 5 times) in the photopolymerization of the calf lens membrane main intrinsic protein (MP26) was found in the presence of HP. Tenfold increases in destruction rates were found in losses of histidine. The MP26 was also photolyzed after tryptic and chymotryptic digestion to MP21, this resulted in an increased photopolymerization in the presence of 1 mM HP. These data suggest an age related increase in sensitivity of the lens fiber membrane proteins to such photoprocesses. The addition of both azide and penicillamine reduces the photosensitized loss of the main intrinsic protein. PMID- 4017618 TI - The interrelationship of tropical disease and mental disorder: conceptual framework and literature review (Part I--Malaria). AB - Substantial interactions between tropical diseases and psychiatric illness have long been recognized, but the impact of biological factors in the field of cross cultural psychiatry has been less well studied than psychosocial factors. In reviewing the literature at the intersection of tropical medicine and psychiatry in order to summarize the existing data base in this field, a generalized interactive model informed by the theoretical contributions of George Engel, the WHO Scientific Working Group on Social and Economic Research, Arthur Kleinman, P. M. Yap, Edward Sapir and others has been developed to serve as a conceptual framework for this analysis of the literature and to guide further research. The clinical literature of tropical medicine and psychiatry which recognizes the significance of concurrent tropical disease and mental disorders is reviewed along with the more specific literature on malaria and concomitant psychiatric illness. Many authors have focused on the role of organic mental disorders, especially in connection with cerebral malaria, but several have also addressed psychosocial parameters through which the interrelationship between malaria and a full range of mental disorders is also mediated. The effects of malaria may serve as biological, psychological or social stressors operating in a cultural context which precipitate or shape features of psychiatric symptomatology. Psychiatric illness may likewise precipitate an episode of malaria with typical symptoms in a patient with a previously subclinical infection. Implications of the literature and this generalized interactive model are considered as they apply to clinical practice, public health and the application of social science theory in medicine. PMID- 4017622 TI - The optically determined corneal and anterior chamber volumes of the cynomolgus monkey. AB - We described an optical method of measuring corneal volume and employed the optical method of Johnson et al. for measuring the volume of the anterior chamber in cynomolgus monkey. In 12 normal monkey eyes, the corneal volume was found to be 40.4 +/- 2.3 microliter (mean +/- S.E.) and the anterior chamber volume was 101.8 +/- 4.2 microliter (mean +/- S.E.). PMID- 4017623 TI - Localization and properties of an immunoreactive protein in bovine ciliary body similar to retinal S antigen. AB - Immunocytochemical studies showed that monoclonal antibodies to bovine retinal S antigen recognize an immunoreactive protein present in the bovine ciliary body epithelium. This protein was purified by DEAE-agarose chromatography and found to have a M.W. of 28,000 daltons by SDS polyacrylamide gel electrophoresis. Crude and purified preparations of this protein cross-react with polyclonal antibodies to retinal S-antigen. The relative reactivity of S-antigen monoclonal antibodies to ciliary body protein was determined by ELISA. Lewis rats immunized with crude and purified ciliary body protein failed to develop experimental uveitis. The results indicate that the ciliary body protein contains an antigenic peptide domain which is similar to that of S-antigen but lacks the immunopathogenic domain. PMID- 4017624 TI - Studies in experimental keratomycosis. AB - The study of experimental fungal infections requires effective animal models. Two such models in the rabbit model have been developed and applied to various aspects of topical antifungal therapy. In these models, the polyenes, as a class, are superior in efficacy to the imidazoles and flucytosine, but efficacy is clearly strain related. Corticosteroids, when administered concomitantly with antifungal agents, adversely influence antifungal activity in vivo. This steroid effect is inversely proportional to the efficacy of the antifungal agent. The corneal epithelium appears to be a significant barrier to the penetration of the polyene antibiotics. Although the predictive power of in vitro susceptibility testing as a guide to in vivo efficacy is uncertain, a correlation was seen between the in vivo and in vitro effect for amphotericin B against three strains of Candida albicans. PMID- 4017625 TI - Transplantation of cultured human retinal epithelium to Bruch's membrane of the owl monkey's eye. AB - Human retinal epithelial cells dividing in culture have been radiolabelled with tritiated thymidine and subsequently transplanted and identified on Bruch's membrane of owl monkey by autoradiography. Such cells have been followed from 2 hours to 7 days after transplantation. The transplant cells reattach within 2 hours to the basement membrane left on Bruch's membrane after the host epithelial cells have been removed by suction after trypsinization. Within 6 to 24 hours they form a layer on Bruch's membrane with junctional complexes between cells and an apical-basal polarity characteristic of such cells in culture or after retinal detachment. After 2 to 7 days multilayers form by continued mitosis but no transplant cells invade the choroid as long as Bruch membrane is intact. Within this time macrophages begin to appear in the choriocapillaris under the transplant. These cells migrate through Bruch's membrane and between the transplant cells but have not been seen phagocytizing transplant cells. Reattachment of the neural retina to the transplant layer has not been attempted but seems technically possible. PMID- 4017626 TI - Experimental investigations of intraocular eicosanoids: cultured human trabecular cells and laser photocoagulation of the rabbit iris. AB - The significance of prostaglandins and other eicosanoids in normal ocular physiology and in ocular disease is not well understood. We have utilized cultured human trabecular cells and an in vivo model of laser-induced inflammation in the rabbit eye to gain information concerning eicosanoid biosynthesis and its regulation in the anterior segment. Further investigations using these experimental paradigms should help to elucidate the physiologic and pathophysiologic roles of eicosanoids in the eye. PMID- 4017628 TI - International symposium on membrane transport mechanisms in the eye. Berlin, West Germany, September 26-29, 1984. PMID- 4017627 TI - Progress toward the establishment of nuclear magnetic resonance measurements as an index of in vivo lens functional integrity. AB - Cataract prevention, delay, or reversal requires in vivo detection of lens changes that initiate the opacification process. The determination of lenticular biochemistry by a noninvasive methodology would represent a major step in the in vivo assessment of lens normalcy. Nuclear magnetic resonance spectroscopy appears to be a promising noninvasive technique to meet this goal. However, the correlation of lenticular "invasive" morphological and physiological data with NMR spectroscopic data in organ culture is necessary for establishing the validity of NMR spectral measurements as an index of lens functional integrity. The implementation of lenticular NMR spectroscopic studies will provide quantitative information such as intralenticular pH, Na+ and K+ ion distributions, lenticular levels of phosphorus-containing metabolites, glycolytic pathway intermediates and the end product lactate, sorbitol pathway activity, and possibly reduced glutathione levels. Development in surface coil NMR spectroscopy which enables the spatial localization of tissue metabolites and advances in the refinements required for quantitation of these results are discussed. These measurements of in vivo lenticular biochemistry will provide the information necessary for the scheduling of anticataract drug therapy as well as an ongoing method for monitoring the efficacy of such treatment. PMID- 4017629 TI - Passive ion fluxes across the corneal endothelium. AB - The deepithelialized cornea is mounted in a chamber and perfused on both surfaces by identical closed systems. The technique allows the continuous measurement of the net water flux and the electrical potential across the preparation as well as the steady state flux of radioactive ions. The permeabilities of pairs of ions in the same direction were compared, and they were found to be closely proportional to their free diffusion constants, suggesting that they passed by way of the intercellular spaces. Technical difficulties prevented a valid determination of the existence of active ion transport, but there was no indication of its presence. PMID- 4017630 TI - The mechanism of fluid and electrolyte transport across corneal endothelium: critical revision and update of a model. AB - A model for endothelial transport is updated to include recent evidence. We discuss electrolyte movements based on a Na+-K+ ATPase, a Na+-H+ exchanger, a Na+ HCO3 coupler, a Cl- -HCO-3 exchanger, a K+-Cl-coupler, and K+ and anion channels. We discuss near-isotonic transport of fluid on the basis of recent findings of high endothelial osmotic permeability. PMID- 4017631 TI - Ion transport mechanisms in cultured bovine corneal endothelial cells. AB - Intracellular potential measurements of confluent monolayers of cultured bovine corneal endothelial cells were used to define passive ion transport processes in these cells. Previous studies (Jentsch et al., J. Membr. Biol. 78:103 (1984); Jentsch et al., J. Membr. Biol. 81:189 (1984] have provided the experimental basis for a cellular model, in which bicarbonate entry across the basolateral membrane is indirectly driven by a Na+/H+-exchanger, which is inhibitable by amiloride (1mM). Bicarbonate and sodium should leave the cell via an electrogenic bicarbonate sodium cotransport, which is inhibitable by the disulfonic stilbene derivates SITS or DIDS. This model is also consistent with results from transendothelial studies. In this paper, we briefly review the evidence we have obtained for this model and demonstrate, that the electrical response to sodium (depolarization upon Na+-removal) is neither due to an inhibition of Na+/K+ ATPase nor explainable in terms of changes in K+-conductance. This is concluded from the observation of these responses in the presence of ouabain (10(-4)M) or barium (1mM). PMID- 4017632 TI - Ocular pharmacology of sulfonamides: the cornea as barrier and depot. AB - In the past five years we have studied the penetration of locally applied sulfonamides into the eye, with a view toward developing new topical carbonic anhydrase inhibitors for the treatment of glaucoma. The drugs varied by 400 fold in their permeability to the anterior chamber and 20,000 fold in permeability to the posterior chamber. We report now on two particular findings related to drug structure: 1) Transcorneal permeability of the ionic or dissociated form of the drug is relatively high -- some 1/4 that of the undissociated form. 2) Depending on the structure, certain compounds are sequestered in the cornea (presumably the stroma) and form a release system into the anterior aqueous. PMID- 4017633 TI - Steady state voltages in the frog lens. AB - Electro-chemical steady state in the lens depends on the transport properties of its various constituent cells. These transport properties, at a minimum, include the active transport of Na/K and the passive leak of Na, K and Cl through membrane channels. The work of Kinsey and Reddy (1), first localized active Na/K transport to the anterior surface cell membranes. In this paper, we estimate that the pump current density is 2 to 4 mu amp/cm2 of surface membrane, by measuring the change in intracellular voltage when the lens is exposed to 100 microM ouabain. Our impedance data suggest the passive leak of K is mostly across the membranes of surface cells, but whether these are anterior or posterior cells is not yet known. Membranes of the fiber cells throughout the volume of the lens appear to have channels that are selective for Na and Cl but few K channels. A simple model of electro-chemical steady state is derived to relate localized transport properties to the resting voltages in the lens. The above described localization of properties predicts radially circulating currents at steady state and spatial gradients in the intracellular and extracellular voltages. These predictions are compared to our measurements of steady state voltages and we find good agreement. PMID- 4017634 TI - Examination of lens calcium balance using 45Ca uptake studies. AB - The utility of 45Ca efflux studies to examine lens calcium balance is limited because of the dominant contribution of efflux from the extracellular space of the lens. On the other hand, examination of lens 45Ca uptake characteristics can generate valuable information regarding the mechanism by which calcium is largely restricted from the intracellular compartment. Such studies have enabled us to demonstrate that the access of calcium to the intracellular compartment is dependent to some extent upon the concentration of calcium in the extracellular environment. Additionally, experimental evidence speaks against extracellular binding of calcium. Finally, lens membrane permeability to calcium appears to be independent of membrane voltage. PMID- 4017635 TI - Effect of corticosteroids on electrolyte transport of the isolated human and rabbit lens. AB - In the isolated human lens, short circuit current was inhibited by pharmacological concentrations of 6-methylprednisolone and opacities occurred in the posterior subcapsular region in some lenses. The effect was seen only when the anterior (epithelial) surface of the lens was exposed. There was an increase of the short circuit current in the rabbit lens by 6-methyl-prednisolone and the lenses remained clear. Methylprednisolone effects were seen in spite of Na-K ATPase inhibition by ouabain. Aldosterone had no effect on the translenticular potential difference, short circuit current and transparency. The data are discussed with respect to corticosteroid receptors in the lens epithelium and to the pathogenesis of steroid-associated cataract in man. PMID- 4017636 TI - Role of calcium in cholinergic stimulation of lacrimal gland protein secretion. AB - To characterize the role of Ca2+ in cholinergic stimulation of lacrimal gland protein secretion, the effects of inhibitors of cellular Ca2+ handling on protein secretion were investigated. Protein secretion was measured from rat exorbital glands using either pieces of gland in perifusion or acini isolated by collagenase digestion. Peroxidase was used as a measure of protein secretion. An inhibitor of Ca2+ influx via voltage sensitive Ca2+ channels (verapamil) at 10( 5) and 5 X 10(-5) M did not alter protein secretion stimulated by the cholinergic agonist carbachol at 10(-5) M. Inhibition of Ca2+ efflux via Na+/Ca2+ exchange by removal of extracellular Na+ or by inhibition of Na+-K+-ATPase activity using ouabain (10(-3) M) or extracellular K+ removal did not stimulate protein secretion. In contrast, inhibition of Ca2+ release from intracellular stores with TMB-8 at 100 micron completely blocked protein secretion stimulated by carbachol at 10(-5) M. Similarly, the Ca2+/calmodulin (CaM) antagonists W-13 and W-12 decreased carbachol-induced protein secretion with potencies similar to those which inhibit Ca2+/CaM dependent processes. We conclude that cholinergic agonists stimulate lacrimal gland protein secretion primarily by mobilizing Ca2+ from intracellular stores and that one mechanism by which this Ca2+ could activate secretion is in conjunction with calmodulin. PMID- 4017637 TI - Secretion of drugs in tears. AB - Secretion in tears has been investigated for a limited number of drugs. Transfer of the free non protein-bound fraction from plasma to tears only can be expected for unionized drugs with sufficient lipid solubility. For acid and basic drugs the correlation of tear: plasma (unbound) ratio is disturbed by variations in tear pH. Within these limitations tear sampling will not be an useful method for drug concentration measurement. PMID- 4017638 TI - Influence of secretagogues on volume and protein pattern in rabbit lacrimal fluid. AB - After certain tear proteins had been found to be markers of duct cell activity in the rabbit lacrimal gland, different secretagogues were tested to increase volume and protein secretion. Carbamyl-choline and the peptides eledoisin and vasoactive intestinal peptide (VIP) stimulated volume flux as well as secretion of the marker proteins indicating duct cell activation. Beta-adrenergic stimulation also increased secretion of a further tear protein. This might indicate that water is secreted by the duct cells. These are stimulated by the secretagogues mentioned above. Beta-adrenergic stimulation might in addition activate the acinar cell system. PMID- 4017639 TI - The structure of tight junctions in the ciliary epithelium. AB - The tight junctions of the ciliary epithelium act as a barrier preventing the passage of blood borne macromolecules into the posterior chamber. The use of the freeze-fracture technique has led to a good knowledge of their morphological pattern in various species. However, in order to attempt a correlation of the morphology of the tight junctions with their physiological properties, their intimate substructure must be considered. As in other glutaraldehyde-fixed epithelia, the tight junctions appear as networks (variable in their apico-basal thickness) of more or less discontinuous P-face ridges and as complementary E face furrows in which some particles or short bars are found. The significance of the discontinuities of ridges has been analysed. The continuity of the junctional fibrils was evident as assessed both by quantitative measurements as well as morphological examination of complementary fracture faces. In addition, the absence of loss of junctional material showed that the integrity of the junction was preserved during the freeze-fracture process, even in conditions where an increase in "transfer" of junctional elements was experimentally induced. Most of all, a "pore system" due to visualizable gaps in the fibrils is not tenable for the ciliary epithelium. Furthermore, the analysis of transition steps at the level of membrane "fusion" showed that the tight junctions of the ciliary epithelium must now be considered as formed by two slightly offset fibrils, one per adjacent plasma membrane. PMID- 4017640 TI - Morphological evidence for the transfer of anionic macromolecules from the interior of the eye to the blood stream. AB - We have either introduced into the vitreous space or perfused through the anterior chamber of macaque monkey eyes two anionic tracers, anionic ferritin (AF) and horseradish peroxidase (HRP) and a cationic probe, cationic ferritin (CF). We have observed that the anionic molecules, but not the cationic one, are transported to the blood stream by plasmalemmal vesicles of the endothelial cells in both the retinal and the iridial vasculature. We suggest that a variety of organic anions of different MW which are commonly present in the eye tissues may be returned to the blood by the same morphological mechanism. PMID- 4017641 TI - A model of corneal re-endotheliazation after surgical trauma. AB - A model for simulating the endothelial damage caused by surgery is described. The model consists of the introduction of a specially constructed instrument into the anterior chamber and using it for scraping the endothelium of a pre-determined, precisely quantifiable area of cornea. The process of healing of the scraped cornea can be followed and measured accurately by biomicroscopy, specular microscopy and histological techniques. The model can be used to study the qualitative and quantitative aspects of endothelium healing and the effects of the various endogenous, exogenous and iatrogenic factors on this process. The preliminary data presented shows that the healed endothelium consists of larger and less densly packed cells. The cell density is reduced by 43.3% after one scraping of 57% of the endothelium and by 69.2% after two such operations. Prolonged mild traumatic iritis causes the appearance of endothelial cells with incongruous shapes. PMID- 4017642 TI - Alterations in ocular and optic nerve blood flow during intraocular surgery in aspirin pretreated rabbits. AB - The effect of intraocular surgery on ocular and optic nerve blood flow was determined in rabbits either untreated or pretreated with aspirin. Surgery was either extracapsular lens extraction through a 100 degrees corneal incision or a sham-operation in which a 45 degrees corneal incision was performed and the lens left in place. In both cases, the incisions were not sutured and the intraocular pressure remained zero for one hour. A (85Sr) radioactive microsphere technique was used to measure blood flow in the iris, scraped ciliary processes, retina, choroid, and optic nerve. In rabbits not receiving aspirin pretreatment, blood flow was statistically increased in all portions of the eye, except the retina and optic nerve, studied for sham-operated eyes, and in the iris and optic nerve in the lens extraction group. In rabbits pretreated with aspirin, blood flow remained at normal levels. These results are consistent with the hypothesis that prostaglandins released during ocular surgery cause increased ocular tissue blood flow. PMID- 4017643 TI - Statistical analysis for experimental models of ocular disease: continuous response measures. AB - Experimental designs in ophthalmologic research frequently treat both eyes of a subject in the same fashion: e.g., therapy with a specific drug or control. In these two-eye designs, observations from the same subject are often positively correlated. Failure to account for this correlation is a serious error which overstates the precision of studies, resulting in falsely significant results. This paper reviews the statistical methods appropriate for studies where endpoints are quantitative. We present: (1) the use of analysis of variance (t test when there are 2 treatment conditions) to estimate differences between all experimental treatments, (2) the use of contrasts to estimate differences between specific treatments, and (3) methods for analysis of data from multiple experiments. Because of the ubiquity of incorrect analysis of data from two-eye designs in the ophthalmologic research literature and the serious consequences of this error, we propose a limited statistical review of manuscripts to ascertain if the statistical analysis matched the experimental design. PMID- 4017644 TI - Ocular fluid dynamics response to topical RU486, a steroid blocker. AB - A steroid antagonist applied to one eye of 18 young pigmented rabbits during a 10 week period caused a statistically significant fall in IOP, but no statistically significant nor clinically relevant change in the rate of aqueous humor turnover. The pressure change is therefore ascribed to an alteration in outflow channels. No changes occurred in a parallel group of 5 animals in which one eye was treated with vehicle and the contralateral eye was untreated. The drug effects became evident after two weeks of application, suggesting that a slow turnover pathway is involved. PMID- 4017645 TI - Corneal penetration and metabolism of the antiherpetic 5-iodo-2'-deoxycytidine. AB - The study of the permeability of the cornea to 5-iodo-2'-deoxycytidine (IDC), an antiherpetic agent was performed in the rabbit. In a first experiment, using 125I IDC eye-drops and a sustained contact between the drug and the cornea, we showed that the penetration of IDC in the aqueous humor was important. In a second experiment, using a HPLC method, we studied comparative ocular penetration and metabolism of IDC and 5-iodo-2'-deoxyuridine (IDU). PMID- 4017646 TI - The persulfates: a triple threat. PMID- 4017647 TI - Association of pili torti and leukonychia. AB - A patient with both pili torti and leukonychia had a family history indicating dominant inheritance for the nail changes. However, no relatives had hair abnormalities. The authors briefly review both of these unusual entities. PMID- 4017649 TI - Cryotherapy of lentiginous mosaicism. AB - Liquid nitrogen cryospray treatments were successfully used to remove unilateral segmental lentigines. The rare disease of lentiginous mosaicism is described. PMID- 4017648 TI - Malassezia folliculitis in immunocompromised patients. AB - Four cases of Malassezia folliculitis in immuno-compromised patients with leukemia, papillary adenocarcinoma of the lung, and chronic renal failure are reported. This condition manifests with multiple bland asymptomatic follicular papules of the trunk and arms. Biopsy specimens show dilated follicles containing unipolar budding yeast forms. Malassezia is a common infection that must be differentiated from the cutaneous manifestations of systemic candidiasis. PMID- 4017650 TI - Cryoanesthesia and electrosurgical treatment of benign skin tumors. AB - Liquid nitrogen spray followed by light electrodesiccation treatment is helpful in the management of flat warts, small skin tags, seborrheic keratoses, and cherry angiomas. Patients experience minimal discomfort and the procedure can be rapidly completed with excellent cosmetic results. PMID- 4017651 TI - Contact dermatitis in cystic fibrosis. AB - Contact dermatitis has not been previously reported in association with cystic fibrosis. We present the case of a 19-year-old nonatopic patient with cystic fibrosis who experienced erythema and vesicles in an area exposed to nickel. PMID- 4017652 TI - Combined surgical treatment of male pattern alopecia. AB - Loss of scalp hair, whether gradual or abrupt, can have devastating effects on a patient's self-image. Restoration of a positive self-image through improved appearance is a primary goal of all cosmetic surgery. Patient selection based on the type of alopecia and the real motivation for surgery is the first step in this metamorphosis. PMID- 4017653 TI - Anthralin cream as short contact therapy for psoriasis. AB - Anthralin is effective in the management of psoriasis. Because of frequent skin irritation, staining of skin and clothing, and patients' difficulty in using stiff paste and ointment preparations in traditional regimens, newer treatment protocols are being evaluated. We report a four-week study of twenty patients using an anthralin cream for thirty-minute short-contact therapy. Both 0.5 percent and 1.0 percent anthralin concentrations were evaluated. We found that short contact therapy with the anthralin cream preparations was effective. In four weeks it resulted in the clearing of treated areas in more than one-third of the patients, and significant improvement in an additional 35 percent. Little difference in efficacy was noted between the 0.5 percent and 1.0 percent concentrations. Most patients found the treatment regimen cosmetically acceptable and experienced minimal problems with staining and skin irritation. PMID- 4017654 TI - Reiter's syndrome with nail involvement: is it psoriasis? PMID- 4017655 TI - Malignant histiocytosis. AB - Malignant histiocytosis, also known as histiocytic medullary reticulosis, is a rare neoplasm of malignant histiocytes. Clinical findings include fever, weight loss, hepatosplenomegaly, lymphadenopathy, anemia, thrombocytopenia, and a rapidly worsening course. Approximately 7 percent of patients have skin manifestations early in the course of their disease. In these patients, diagnosis based on examination of a skin biopsy specimen may be crucial. A case of malignant histiocytosis is presented in which the diagnosis was first suggested by findings on the skin biopsy specimen. PMID- 4017656 TI - Needle aspiration for diagnosis of cellulitis. AB - Diagnosing the causative agent of bacterial cellulitis is difficult. Blood culturing and needle aspiration have been used: the former has an extremely low sensitivity, the yield of the latter ranges from 4 to 42 percent. A retrospective study was conducted to determine the diagnostic success of needle aspiration and culture of the leading edge of cellulitis with a 21 to 22 gauge syringe and conventional bacteriologic culture of blood in determining the agent that causes acute cellulitis. This agent was determined in 33 percent of patients by needle aspiration and in 4 percent using blood cultures. PMID- 4017657 TI - Hairy elbows. AB - Hairy elbows (hypertrichosis cubiti) represent an uncommon variety of localized hypertrichosis not associated with significant medical problems. This hypertrichosis occurs in young children and may occur sporadically or possibly be genetically determined. The process is of cosmetic concern alone, and reassuring the parents is the only therapy necessary. PMID- 4017658 TI - Pseudomelanoma in a black patient. AB - A worrisome lesion in a 62-year-old black man prompted a review of the differential diagnosis of pigmented lesions involving palmar skin. PMID- 4017659 TI - Zosteriform connective-tissue nevus. AB - Zosteriform connective-tissue nevus, because of its distribution and histopathologic characteristics, is considered to be a separate entity. The only previous case of zosteriform connective-tissue nevus to be reported in the American literature was in 1944. We report and discuss a similar case. PMID- 4017660 TI - Dermal leishmaniasis after kala-azar infection: successful treatment with rifampin. AB - A patient with dermal leishmaniasis subsequent to kala-azar was treated with sodium stibogluconate, but the condition did not improve. The patient was then treated with rifampin which has not been used to treat this condition in the past. All clinical features cleared spontaneously by six weeks. No overt disease was noted during the next three months. Rifampin can therefore be used to treat post-kala-azar dermal leishmaniasis when standard procedures are ineffective. PMID- 4017661 TI - Effects of maintaining normal plasma colloid osmotic pressure on renal function and excretion of sodium and water after major surgery. A randomized study. AB - A prospective, randomized study of patients undergoing abdominal aortic surgery was undertaken to determine the effects of maintaining normal plasma colloid osmotic pressure (COPp) on postoperative renal function and excretion of water and electrolytes. Two groups of 13 patients were given whole blood transfusions to replace blood loss. One group (ALB) received 80 g albumin on the day of operation and 20 g albumin the following three days. The other group (NON-ALB) received no extra albumin. The glomerular filtration rate (GFR) did not change significantly from preoperative values on the first or fourth postoperative day in any of the groups. The differences between the groups were non-significant. COPp could not be correlated to either GFR or sodium or fluid balances. Postoperative sodium and water retention was found to depend on the amount of infused sodium. Unexplained fluid shifts to a "third space" did not occur. Administration of albumin in addition to quantitative blood loss replacement is unnecessary and expensive. PMID- 4017662 TI - Lymphocytic adenohypophysitis. A review and a case. AB - An unconscious, 29-year-old woman was taken to hospital where, 28 hours after admission, she succumbed to an intractable shock. Autopsy disclosed a lymphocytic adenohypophysitis (LAH). Judged by experiments on animals and by antibody examinations in women during puerpera, LAH is probably an autoimmune disease belonging to a group of autoimmune endocrinopathies, from which one or more is seen with LAH. The description of the present case is accompanied by a description of the disease in eight cases, all women; in only one patient was the diagnosis not made by autopsy. The patients can be divided into two groups, one group consisting of postmenopausal women, another who all became ill approximately one year after giving birth. It is suggested that this histopathological diagnosis also has a clinical significance. PMID- 4017663 TI - Acute abdomen in rheumatoid arthritis due to mesenteric arteritis. A case report and review. AB - A 69-year-old woman with seropositive rheumatoid arthritis since the age of 54 developed severe abdominal pain, and laparotomy was performed. Due to perforation of the ileum, there was generalised peritonitis. The histological examination showed mesenteric rheumatoid arteritis. Only a few cases like this are described in the literature. Most of the patients were males, and the mortality was high. When a patient with rheumatoid arthritis develops abdominal pain, mesenteric arteritis may be the cause. No definitive therapy is available, but prompt surgical intervention followed by anticoagulants has been recommended. For the treatment of rheumatoid vasculitis as such, corticosteroids in high doses, cyclophosphamide and plasma exchange have been used separately with beneficial effects. PMID- 4017664 TI - Transbronchial needle aspiration. Is it coming of age? PMID- 4017665 TI - Chest CT in the staging of lung cancer. PMID- 4017666 TI - Propafenone. PMID- 4017667 TI - Of wind and song. PMID- 4017668 TI - Ventilation-perfusion relationships in symptomatic asthma. Response to oxygen and clemastine. AB - Continuous distributions of ventilation-perfusion (VA/Q) ratios were measured in ten subjects with moderately severe symptomatic asthma. Six of the subjects had only minimal VA/Q inequality (mean log SD of bloodflow 0.5) despite having airways obstruction similar to that in the four subjects with marked VA/Q inequality (mean log SD of bloodflow 1.0). The six patients with minimal VA/Q inequality developed marked widening of their VA/Q distributions while breathing 100 percent oxygen (mean log SD bloodflow 1.1), and four of these patients maintained more modest widening after receiving an intravenous antihistamine, clemastine (mean log SD bloodflow 0.75). The four subjects with a wide control VA/Q distribution showed smaller changes while breathing pure oxygen and no change after receiving clemastine. FEV1 improved with clemastine treatment in the first four patients only. The results suggest that the majority of patients with moderately severe asthma have compensatory pulmonary vasoconstriction, causing better VA/Q matching which is responsive to hypoxia and, possibly, histamine. The data demonstrate a relationship between active compensatory vasoconstriction and airway sensitivity to antihistamine. PMID- 4017669 TI - Comparative effects of oral and inhaled verapamil on antigen-induced bronchoconstriction. AB - We investigated the comparative effects of oral and inhaled verapamil on specific airway conductance (SGaw) and allergic bronchial reactivity. Ten asymptomatic subjects with ragweed hypersensitivity and a history of bronchial asthma were studied on four different days, without and with pre-treatments by oral (160 mg) or inhaled (20 mg) verapamil. Bronchial reactivity was measured as the cumulative provocative dose of ragweed antigen which caused a 35 percent decrease in SGaw, ie PD35. The amount of inhaled verapamil actually deposited in the tracheobronchial tree was estimated to be 0.56 mg. Mean SGaw was not affected by either mode of administration; mean SGaw (SE) was 0.13(.02) and 0.12(.02) L/sec-1 before and .14(.02) and 0.12(.02) L/sec-1 after oral and inhaled verapamil, respectively. Mean (SE) PD35 was reproducible on two control days, ie 0.9(.4) and 0.8(.4) breath units, respectively. Inhaled verapamil increased mean PD35 to 18.8 (10.8) breath units (p less than 0.02), while oral verapamil had no significant effect on mean PD35. This study demonstrates that route of administration of calcium antagonist verapamil is an important factor in protection against antigen induced bronchoconstriction. Inhalation of verapamil appears to be more effective than oral administration. PMID- 4017671 TI - Ventricular arrhythmias during insertion and removal of pulmonary artery catheters. AB - The incidence and significance of the development of ventricular arrhythmias during insertion and removal of pulmonary artery monitoring catheters were determined in stable postcardiac surgical patients. Insertion of 173 (69 percent) of 250 catheters was associated with ventricular arrhythmias and removal in 158 (63 percent) of these catheters (p greater than 0.05). All arrhythmias resolved spontaneously. Patients who underwent valve replacement showed significantly fewer arrhythmias during withdrawal than those who underwent a coronary artery bypass operation (p less than 0.025). Factors significantly influencing the incidence of ventricular arrhythmias during removal were increased postoperative CK-MB levels (p less than 0.025) and cardiac index (p less than 0.025). PMID- 4017670 TI - Minimal effect of alcohol ingestion on breathing during the sleep of postmenopausal women. AB - Eighteen asymptomatic postmenopausal women volunteered to ingest 2 ml of 100 proof vodka per kg of body weight in orange juice on one night and a placebo on another. Overnight sleep monitoring was performed immediately thereafter. Alcohol ingestion caused reduction in total sleep time from 329 to 281 minutes and a decrease in rapid eye movement sleep. There was no difference from placebo in the number of episodes of apnea or hypopnea, or in the frequency, length, or severity of oxygen desaturation. In contrast to the effects of alcohol ingestion in men, the effects on breathing and oxygenation are minimal during the sleep of women if this amount of alcohol is ingested. PMID- 4017672 TI - Aerosol penetration and mucociliary transport in the healthy human lung. Effect of low serum theophylline levels. AB - The effect of theophylline on the penetration of an inhaled radioaerosol in the lung, bronchial clearance, and tracheal mucociliary transport rate (TMTR) was investigated in 13 healthy volunteers. Following a randomized, double-blind, crossover protocol, subjects ingested 4 mg/kg twice daily of theophylline or placebo for three days which resulted in stable, low therapeutic serum levels. Aerosol penetration, assessed by the skew of the initial distribution of lung radioactivity, was more peripheral (p less than 0.025) with theophylline, indicating bronchodilation that was not detectable by standard pulmonary function tests. The TMTR increased in ten of 13 subjects after theophylline, but not to a significant level. Bronchial clearance was not significantly different with theophylline despite the longer clearance pathway created by the increased peripheral aerosol deposition. This finding suggests that mucus transport rates in the intrapulmonary airways were increased by theophylline. PMID- 4017673 TI - Pulmonary function in singers and wind-instrument players. AB - Previous studies suggest that pulmonary function of singers and wind-instrument players may be better than normal control subjects due to breath-control training; however, prior studies were poorly controlled or limited in scope. In the present study, we compare 34 singers and 48 wind instrumentalists with a control group of 31 string or percussion instrumentalists using a pulmonary questionnaire, measurements of inspiratory and expiratory pressures, and spirometry. We found no significant difference between groups in maximum voluntary ventilation, forced expiratory volume in one second (FEV1), forced vital capacity (FVC), mean forced expiratory flow during the middle half of the FVC, the FEV1/FVC, peak expiratory pressure, or peak inspiratory pressure, independently or when corrected for age, sex, height, weight, years performing, smoking, presence or absence of cough, or sputum production. Smoking correlated negatively with measurements of pulmonary function in all groups. There was evidence of a heightened awareness of health among singers, who exercised more and smoked less than their colleagues. The differences in health habits may account in part for the myth of improved pulmonary volumes among singers. PMID- 4017674 TI - Roentgenographic evaluation of mediastinal nodes for preoperative assessment in lung cancer. AB - Evaluation of mediastinal nodal metastases is a critical step in the assessment of potential surgical candidates with lung cancer. Mediastinal tomography (TOMO) and chest computerized tomography (CT) visualize the mediastinal nodes more clearly than a chest roentgenogram (CXR). A prospective study was undertaken to determine the clinical value of these three tests for mediastinal staging in 102 surgical patients with lung cancer. All patients underwent thoracotomy and mediastinal nodal dissection. The roentgenographic findings were compared with the histologic evaluation of paratracheal, tracheobronchial angle, aortic window, subcarinal, and inferior pulmonary ligament nodes. TOMO, and especially CT, correctly predicted the size and location of mediastinal nodes; however, the overall accuracies were CXR (74 percent), TOMO (74 percent), CT (61 percent). These results demonstrated that the improvement in mediastinal imaging is counteracted by the fact that enlarged nodes need not contain metastases and normal-appearing small nodes may harbor microscopic disease. Computed tomography and TOMO had little clinical impact on the assessment of mediastinal nodes in potential surgical candidates with lung cancer. PMID- 4017675 TI - Electrophysiologic evaluation of phrenic nerves in severe respiratory insufficiency requiring mechanical ventilation. AB - Diaphragmatic paralysis in patients with respiratory insufficiency compounds the problems in the management. In the presence of lower lobe atelectasis, pleural effusion, or a patient's poor respiratory effort, fluoroscopic examination is often not a reliable way to diagnose diaphragmatic paralysis. We observed that transcutaneous phrenic nerve stimulation in the neck and recording the diaphragmatic potentials from electrodes placed on the lower part of the chest is a simple, reliable, and noninvasive technique to diagnose diaphragmatic dysfunction at the bedside in critically ill patients. In 14 postoperative patients and one with cervical spinal cord injury with respiratory failure, we found ten patients who showed phrenic nerve dysfunction. Besides diagnostic utility, the electrophysiologic evaluation of phrenic-diaphragmatic function provides critical information needed for therapy. PMID- 4017676 TI - Experience with surgery for thymoma associated with pure red blood cell aplasia. Report of three cases. AB - We present three cases of thymoma associated with pure red blood cell aplasia in which thymomectomy and thymectomy were performed. Case 1, a patient with pure red blood cell aplasia and hypogammaglobulinemia, was treated after surgery with immunosuppressive agents. She did not show any remission and died eight months after the operation. Case 2, a patient with pure red blood cell aplasia alone, showed transient erythropoiesis only in the early post-operative period and died one year and seven months after the operation. Patient 3 had pure red blood cell aplasia alone before surgery and was treated after surgery with prednisolone and fluoxymesterone. He showed good remission from the aplasia after these treatments; however, myasthenia gravis appeared seven months after the operation. These results seem to show that such combined therapy as applied in case 3 may be effective for some of the patients with pure red blood cell aplasia and thymoma; however, the effects of thymomectomy or thymectomy (or both) are still controversial for the treatment of pure red blood cell aplasia. PMID- 4017677 TI - Respiratory manifestations in primary Sjogren's syndrome. A clinical, functional, and histologic study. AB - Thirty-six patients with primary Sjogren's syndrome were evaluated for respiratory manifestations using clinical, roentgenologic, functional, and in five cases, histologic criteria. Twenty seven patients (75 percent) had evidence of respiratory involvement, usually occurring early in the course of the disease. Diffuse interstitial lung disease was most common (25 percent) followed by small airways disease (22 percent), desiccation of upper respiratory tract (17 percent) and large airways obstruction (8 percent). There was no patient with pleural effusion. Transbronchial lung biopsy of five patients studied revealed interstitial pathology ranging from dense lymphocytic infiltrates to interstitial fibrosis. Roentgenologic evaluation was often suggestive of interstitial lung disease but did not correlate with functional or histologic findings. PMID- 4017678 TI - Subcutaneous calcifications masquerading as pulmonary lesions in long-term hemodialysis. Review of nodular pulmonary opacities in the population undergoing hemodialysis. AB - Calcification of soft tissue frequently occurs in patients undergoing hemodialysis for chronic renal failure and involves the arteries, eyes, periarticular regions, lungs, heart, abdominal viscera, subcutaneous tissues, and skin. In this report, two such patients are described who presented with apparent pulmonary nodules on their chest roentgenograms obtained on admission. By the use of tomograms and apical lordotic views, both proved to have extrapulmonary calcific deposits in the subcutaneous tissues overlying the upper pulmonary zones. The tendency for these collections to undergo progression, regression, or pseudocavitation is illustrated. Definitive radiographic localization of lesions projecting over the pulmonary fields in patients undergoing hemodialysis is emphasized because of the significantly increased incidence of infection (including tuberculosis), septic embolism, and carcinoma. PMID- 4017679 TI - Acute effects of oxygen treatment upon information processing in hypoxemic COPD patients. AB - The present study investigated the effects of oxygen therapy upon human information processing for hypoxemic COPD patients. Each of ten patients was admitted to a general clinical research center for a two-day period. In a randomly counter-balanced factorial design, patients breathed either room air or enriched oxygen for either six hours or 20 minutes prior to testing. The tests evaluated speed of information processing, ability to detect correct sequence of tones, and serial memory. In addition, patients were evaluated on critical flicker fusion and story recall. The results suggested that acute oxygen therapy does not reverse information processing deficits observed in hypoxemic COPD patients. PMID- 4017680 TI - Stenosis of main bronchi mimicking fixed upper airway obstruction in sarcoidosis. AB - An unusual site and cause of disabling inspiratory and expiratory airflow limitation mimicking fixed upper airway obstruction is reported in two patients with sarcoidosis who had stenosis of almost the entire lengths of both main bronchi. The observed flows were consistent with a cross sectional airway diameter of 3 mm. The lumen of the trachea and proximal airways was not compromised. PMID- 4017681 TI - Pharmacokinetics of tobramycin in patients with cystic fibrosis. Implications for the dosing interval. AB - The pharmacokinetics of tobramycin were evaluated in 15 patients (8 to 22 years of age) with cystic fibrosis (CF). A dose of 3.0 to 3.3 mg/kg of body weight was given intravenously over 20 minutes, and concentrations in serum were followed up to eight hours after initiation of the infusion. In the calculation of pharmacokinetic parameters, a two-compartment open model was used. The elimination half-life of the drug was highly inversely correlated with age (p less than 0.0004), and body weight (p less than 0.00002). Total body clearance (TBC), and volume of distribution at steady state (VDSS) were directly correlated with age and body weight. However, when TBC and VDSS were corrected for BSA, no correlation could be demonstrated. The mean one-hour and eight-hour serum concentrations of tobramycin were 5.40 and 0.45 microgram X ml-1, respectively. Between patients, considerable differences were found in the time after administration at which the serum concentration decreased below 1 microgram X ml 1. This interpatient variation has clinical implications for tobramycin therapy in CF, in particular for the dosing interval. PMID- 4017682 TI - Lupus lung. AB - The morphologic findings from 18 autopsy lungs of systemic lupus erythematosus were studied. Each case revealed varying degrees of pleuropulmonary disease. A universal feature was visceral pleural thickening, while findings present in more than one half of the cases included pulmonary congestion (17/18) and edema (15/18), pleural adhesions (11/18) and pleural effusions (10/18) and intraalveolar hemorrhage (10/18). Also seen were bronchopneumonia (9/18), interstitial fibrosis (6/18), cytomegalovirus infection (3/18), interstitial pneumonitis (2/18), hyaline membranes (2/18), and acute vasculitis (1/18) and pleuritis (1/18). These results, together with those of previously reported studies of lupus lung, establish that although certain characteristic pleuropulmonary disease processes are frequently found at autopsy, none is a highly specific marker for the disease. PMID- 4017683 TI - Dyspnea, fever and miliary pattern. PMID- 4017684 TI - How to survive a case presentation. PMID- 4017685 TI - Outpatient dobutamine infusion using a totally implantable infusion pump for refractory congestive heart failure. AB - A patient with refractory congestive heart failure was treated, on an outpatient basis, with intermittent dobutamine using a totally implantable infusion pump. Dobutamine was infused for 48 hours every week and resulted in sustained clinical improvement. Symptoms and signs of congestive heart failure remained well controlled until his death from a stroke eight months after implantation of the pump. PMID- 4017686 TI - Hypoplastic coronary arteries and high takeoff position of the right coronary ostium. A fatal combination of congenital coronary artery anomalies in an amateur athlete. AB - This report describes a previously unrecognized combination of congenital coronary artery abnormalities in the heart of a 30-year-old amateur athlete who died suddenly during a basketball game. Both right and left circumflex coronary arteries were half of their normal length (hypoplastic) decreasing posterior ventricular myocardial perfusion. In addition, the right coronary ostium rose 5 mm above the sinotubular junction (high takeoff position), which also contributed to decreased right coronary artery perfusion. This combination of congenital coronary arterial lesions should be added to the list of structural cardiac defects associated with exercise-related sudden death. PMID- 4017687 TI - Surgical management of recurrent spontaneous pneumothorax during pregnancy. AB - We report three cases of recurrent spontaneous pneumothorax associated with pregnancy. All three cases had apical bullectomies during their pregnancies. PMID- 4017688 TI - Acute mercury poisoning with severe chronic pulmonary manifestations. AB - This report describes a patient who developed acute chemical pneumonitis following overexposure to metal mercury vapor. The exposure occurred in a gold extraction facility where a gold-mercury amalgam was heated in a confined area. Prompt treatment with penicillamine and corticosteroids was instituted; radiologic pulmonary infiltrates disappeared within a week, but there was little change in the pulmonary function abnormalities (restriction and diffusion impairment) over the period of 11 months of follow-up. This raises the possibility of persistent pulmonary function impairment after metal mercury vapor induced chemical pneumonitis. PMID- 4017689 TI - Polymyositic heart disease. AB - There is an apparent correlation between the severity and duration of skeletal muscle involvement, cardiac manifestations and the extent of conduction system disease in polymyositis. Cardiac involvement during the course of polymyositis has been recognized as one of the typical features of skeletal muscle myositis. We report a patient with polymyositis in whom bifascicular block, prolonged P-R interval and congestive heart failure appeared three years before any clinical or laboratory evidence of active skeletal muscle myositis. To the best of our knowledge, this is the first report of polymyositis where cardiac manifestations preceded those of skeletal muscle myositis. PMID- 4017690 TI - Pulmonary A-V communications in COPD. PMID- 4017691 TI - Rounded atelectasis or pleuroma? PMID- 4017692 TI - Psyllium--a gum, not a protein. PMID- 4017693 TI - Correction. Respiratory drive in non-smokers and smokers assessed by passive tilt and mouth occlusion pressure. PMID- 4017694 TI - Intracranial metastases in the initial staging of bronchogenic carcinoma. PMID- 4017696 TI - Radiotherapy alone for "nonoperability"? PMID- 4017695 TI - Accuracy of 99mTc gated blood pool imaging. PMID- 4017697 TI - Recent advances in the management of obstructive airways disease. Auxiliary MDI aerosol delivery systems. AB - Aerosol delivered through metered-dose inhalers (MDI) offers a potentially convenient way to deliver bronchodilator agents and corticosteroids to the lungs of patients with asthma and COPD. Unfortunately, most patients are unable to coordinate satisfactorily their actuation with inhalation, a problem overcome by using auxiliary MDI aerosol delivery systems. Left to their own judgment, patients often inhale the aerosol with a high inspiratory flow rather than slowly to produce optimal aerosol deposition within the airways. This problem has been corrected by one of the auxiliary MDI aerosol delivery systems (InspirEase) through auditory, visual, and tactile feedback mechanisms. MDI devices release aerosol at a high jet velocity in large particle sizes, depositing most of the aerosol in the oropharynx which can lead to potential systemic absorption of adrenergic agonists with CNS and cardiovascular side effects, oral thrush, and suppression of adrenocortical activity. All the auxiliary MDI aerosol systems promote delivery of small aerosol particles and markedly diminish oropharyngeal impaction. Of all the systems, only InspirEase provides volume and flow feedback controls to ensure an optimal inhalation maneuver. Auxiliary MDI aerosol systems should always be used for aerosolized corticosteroid administration because they minimize oropharyngeal deposition and improve aerosol delivery efficiency. PMID- 4017698 TI - Recent advances in the management of obstructive airways disease. Miami, Florida, February 1-2, 1985. PMID- 4017699 TI - The objective measurement of breathlessness. AB - Both direct and indirect psychophysical methods can be used to measure breathlessness. With indirect methods, detection thresholds can be defined. Direct methods are easier to apply and give more information than indirect methods. Direct methods include interval (partition) and ratio scales, which are easy to apply; both have advantages and disadvantages. The selection of scale depends largely on the question addressed. For comparison across individuals or for the measurement of absolute magnitude (however imprecise), simple category scales are adequate and useful. Open magnitude scaling is best used to define the stimulus parameters influencing perceptual magnitude. Comparison across groups or individuals using exponents as an index of perceptual sensitivity should be interpreted with caution. Where possible, alternative methods should be used to validate differences found. The age-old bias against sensory measurement may be in part our inability to understand the sensory mechanisms and have little to do with the validity of the measurements. PMID- 4017700 TI - Back to basics in health care for foster children. PMID- 4017701 TI - Healing and the arts. PMID- 4017702 TI - Keeping troubled teens at home. PMID- 4017703 TI - In a different light: a feminist perspective on the role of mothers in father daughter incest. PMID- 4017705 TI - Are girls different? Gender discrepancies between delinquent behavior and control. PMID- 4017704 TI - Feminist issues in teenage parenting. PMID- 4017706 TI - Treating abusive parents. PMID- 4017707 TI - Caring for abused preschoolers. PMID- 4017708 TI - Group home failures in juvenile justice: the next step. AB - The author demonstrates that young people who fail in open group homes for status offenders often receive the secure placements that deinstitutionalization was designed to avoid, and that funding regulations may encourage group homes to avoid working with the most difficult youths. PMID- 4017709 TI - Court orders and custody evaluations in Israel. AB - Seven categories of concern entered into custody judgments--continuity, emotional welfare, support systems, children's wishes, parental agreement, caretaking, and child abuse. The literature points to the first four categories and caretaking as vital considerations for children's best interests. Beyond these findings, visiting rights were granted in all cases for the noncustodial parent, the family was always seen together, and the children were involved in discussion in the majority of cases. It is hoped that this study of social work practice in one country will add insight into the complex issue of custody and aid in the improvement of care for all children. PMID- 4017711 TI - A parent aide program: record keeping, outcomes, and costs. AB - As the use of parent aides grows, it is important that plans for developing and administering the services be carefully drawn to enhance the service. The record keeping system described here evolved in direct response to program objectives and has helped maintain those objectives. It should be emphasized that although the procedures involved appear time consuming and perhaps troublesome, they play an important part in saving program time overall and making an effective service available to as many clients as possible. When the costs of parent aides are compared with those of other services, the results show that the time-limited, goal-oriented focus of this program allows effective services to be delivered economically. PMID- 4017710 TI - Child sexual abuse prevention: does it work? AB - Child sexual abuse prevention programs designed to teach children ways to recognize, resist, and report sexual abuse have proliferated in the past five years. The authors evaluate one such program to find out what children know before instruction, if they learn how to prevent sexual abuse, and how they and their parents and professionals who work with children react to such a program. PMID- 4017712 TI - Adapting Multiple Impact Therapy for day treatment intake. AB - Presented here is a shortened version of Multiple Impact Therapy, intended primarily for pre-intake evaluation for a day treatment program for emotionally disturbed children. PMID- 4017713 TI - [Fascial compartment syndromes in the upper limb]. PMID- 4017714 TI - [Imaging of Dupuytren's disease with a scanning electron microscope]. PMID- 4017715 TI - [Rare radiological symptoms of primary spinal stenosis]. PMID- 4017716 TI - [Results of treatment of spinal fractures by the method of spring alloplasty depending on the mechanisms of injury]. PMID- 4017717 TI - [Risk factors in the development of secondary coxarthrosis]. PMID- 4017718 TI - [A case of functionally treated osteochondrosis dissecans of the hip joints]. PMID- 4017719 TI - [Bilateral alloplasty of hip joints in the treatment of coxarthrosis]. PMID- 4017720 TI - [Derotation osteotomy of the humerus in the treatment of perinatal paralysis of the Duchenne-Erb type]. PMID- 4017721 TI - [Open dislocations of the ankle joint and peritalar dislocations]. PMID- 4017722 TI - [Preoperative risk factors in wound healing after surgery of the locomotor system in relation to surgical patients]. PMID- 4017724 TI - [An attempt at using controlled therapeutic hemodilution in non-healing wounds and bedsores]. PMID- 4017723 TI - [Phagocytic and bactericidal capacity of granulocytes of peripheral blood in patients with chronic post-traumatic osteitis after treatment with staphylococcal anatoxin]. PMID- 4017725 TI - [Multifocal injuries of bones in our cases and their treatment]. PMID- 4017726 TI - [Reconstruction of the humeral shaft in children with anatomical resection of cystoid changes with simultaneous implant of autologous fibula]. PMID- 4017727 TI - [Surgical abdomen in the acquired immunodeficiency syndrome]. PMID- 4017728 TI - [Eosinophilic cystitis. 2 cases]. PMID- 4017729 TI - [Iatrogenic perforation of the esophagus. Analysis of 27 cases]. PMID- 4017730 TI - [Cystic dilatation of the common bile duct. 4 cases, 2 with degeneration]. PMID- 4017731 TI - [Bilateral wrist fractures]. PMID- 4017732 TI - [AS 800: an artificial sphincter for postoperative incontinence in men]. PMID- 4017733 TI - [Esophagotracheal fistulas after respiratory intensive care. Apropos of 19 cases]. PMID- 4017734 TI - [Adenocarcinoma of the endometrium. Anatomo-pathological evaluation. 330 bilateral iliac lymphadenectomies]. PMID- 4017735 TI - [Hyperprolactinemia and ovulatory dysfunction]. PMID- 4017736 TI - [Polycystic ovarian syndrome treated with Chinese traditional medicine; analysis of 117 cases]. PMID- 4017737 TI - [Analysis of 91 cases of cervical endometriosis]. PMID- 4017738 TI - [Long-term follow-up study of endometrial cancer]. PMID- 4017739 TI - [Endometrial estrogen and progesterone receptors in women wearing intrauterine contraceptive devices]. PMID- 4017740 TI - [G-banded chromosomes of cord blood in newborn infants]. PMID- 4017741 TI - [Graphicostatistical analysis of 150 cases of the fetus in occipito-posterior position]. PMID- 4017742 TI - [Uterine anomalies complicating pregnancy; report of 77 cases]. PMID- 4017743 TI - [Neonatal intracranial haemorrhage and causal analysis of the diagnostic errors; autopsies of 46 cases]. PMID- 4017744 TI - [Collective review of 14 cases of rare congenital malformations]. PMID- 4017745 TI - Caffeine induces sister-chromatid exchanges during the whole S-phase of the cell cycle. AB - The capacity of caffeine to induce sister chromatid exchanges (SCEs) in different cell cycle stages and the proliferation kinetics were studied. Continuous treatment with this xanthine during the whole second cycle significantly increased the baseline SCE frequency. Pulse-treatment experiments showed that the induction of SCEs by caffeine, which was dose-dependent, was restricted to the S phase of the cell cycle without effect on G1 or G2 cells. Moreover, unlike other SCE-inducing agents, such as DNA-synthesis inhibitors and DNA-damaging agents, caffeine produced similar SCE increases in cells treated at different times throughout the S-phase. In the light of Painter's model for SCE formation and the known effects of caffeine on the DNA replication pattern, the most likely mechanism of SCE induction by caffeine is an increase in the number of DNA replication sites. PMID- 4017746 TI - Strand breaks arising from the repair of the 5-bromodeoxyuridine-substituted template and methyl methanesulphonate-induced lesions can explain the formation of sister chromatid exchanges. AB - 5-Bromodeoxyuridine (BrdU)-induced sister chromatid exchanges (SCEs) are mainly determined during replication on a BrdU-substituted template. The BrdU, once incorporated, is rapidly excised as uracil (U), and the gap is repaired with the incorporation of BrdU from the medium, which leads to further repair. During the second S period in BrdU medium, this process continues as the strand acts as template. Experiments suggest that 3-aminobenzamide (3AB) delays the ligation of the gaps formed after U excision, resulting in enhanced SCE levels during the second cycle of BrdU incorporation. When normal templates of G1 cells are treated before BrdU introduction with methyl methanesulphonate (MMS), 3AB in the first cycle doubles the MMS-induced SCEs but has no effect on them during the second cycle. When the BrdU-substituted template is treated with MMS in G1 of the second cycle, 3AB again doubles the SCEs due to MMS and also enhances the SCEs resulting from delays in ligation of the gaps following U excision in the BrdU-substituted template. The repair processes of MMS lesions that are sensitive to 3AB and lead to SCEs take place rapidly, while the repair process of late repairing lesions that lead to SCEs appear to be insensitive to 3AB. A model for SCE induction is proposed involving a single-strand break or gap as the initial requirement for SCE initiation at the replicating fork. Subsequent events represent natural stages in the repair process of a lesion, ensuring replication without loss of genetic information.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4017748 TI - [Value of echocardiogram-measured right ventricular systolic time intervals in the assessment of pulmonary hemodynamics]. PMID- 4017747 TI - Mass characteristics of DNA obtained from chromosomes of a human carcinoma cell line. AB - Sedimentation studies of DNA from chromosomes extracted from human mitotic cells showed that high-molecular-weight DNA can be obtained if cell hypotonic treatments and prolonged metaphase blocks are avoided. Two types of large double stranded DNA were observed. One of these (Mr = 2.5 X 10(8)) appeared as a size class with characteristics reminiscent of the chromosomal DNA subunit hypothesis. However, this DNA is the decay product of larger molecules, whose minimum molecular weight is 6 X 10(8). PMID- 4017749 TI - [Electrophysiologic effect of intravenous amiodarone on patients with paroxysmal supraventricular tachycardia]. PMID- 4017750 TI - [Renal tubular function changes in lupus nephritis]. PMID- 4017751 TI - [Determination of urinary bradykinin in liver cirrhosis]. PMID- 4017752 TI - [Sjogren's syndrome with pulmonary manifestations: 47 case reports]. PMID- 4017753 TI - [53 cases of brain stem encephalitis]. PMID- 4017754 TI - [Mirror writing]. PMID- 4017755 TI - [Allergic encephalopathy in scleroderma: a case report]. PMID- 4017756 TI - [Socio-familial participation in the prevention and treatment of psychotic disorders: a pilot study in Haidian District of Beijing]. PMID- 4017757 TI - [Psychological test of overinclusion in relatives of the immediate family of schizophrenics]. PMID- 4017758 TI - [575 cases of suicidal behavior by taking poison]. PMID- 4017759 TI - [Psychotic symptoms in 122 cases of affective psychosis]. PMID- 4017760 TI - [Catatonia and mania: report of a case]. PMID- 4017761 TI - [Cerebrospinal fluid cells as seen under transmission electron microscopy]. PMID- 4017762 TI - [Spectrographic analysis of the cerebrospinal fluid in cerebrovascular diseases]. PMID- 4017763 TI - [Changes in serial cerebrospinal fluid immunoglobulin parameters in acute cerebrovascular diseases]. PMID- 4017764 TI - [Effect of functional and angiogenic headache on nailfold microcirculation]. PMID- 4017765 TI - [Multiple primary malignant lesions in colorectal carcinoma]. PMID- 4017766 TI - [Intestinal obstruction due to old peritoneal tuberculosis]. PMID- 4017767 TI - [Transabdominal resection of rectal cancer with preservation of the anus and pull through of the colon]. PMID- 4017768 TI - [Vascular variations encountered during toe transplantation and its management]. PMID- 4017769 TI - [Study and use of the spinal column scale]. PMID- 4017770 TI - [X-ray observations on anterior drawer test in rupture of the lateral ligament of the ankle]. PMID- 4017771 TI - [Impaction-osteotomy in the treatment of genu varum and genu valgum]. PMID- 4017772 TI - [Tibia vara: report of 12 cases]. PMID- 4017773 TI - [Serum potassium changes following cardiopulmonary bypass in children]. PMID- 4017774 TI - [Fractures of the first or second rib in chest injuries: report of 97 cases]. PMID- 4017775 TI - [Operative management of esophageal perforations]. PMID- 4017776 TI - [Repair of a scarring alopecia defect with a single-pedicled scalp flap]. PMID- 4017777 TI - [Hymenal fimbria: report of 31 cases]. PMID- 4017778 TI - [Biologic and morphologic characteristics of the BCaP-37 human breast cancer cell line]. PMID- 4017779 TI - [Anti-infectious function of the rabbit spleen]. PMID- 4017780 TI - [Evaluation of deep venous thrombosis of the legs: clinical observations on the relation to manifestations]. PMID- 4017781 TI - [Merthiolate-preserved homografts for arterial transplantation: surgery and long term results]. PMID- 4017782 TI - [Analysis of trace elements in the hair in patients with biliary stones]. PMID- 4017783 TI - [Metronidazole protects the appendectomy wound from infection]. PMID- 4017784 TI - [Macrophages in giant cell tumors of bones]. PMID- 4017785 TI - [Arterial blood gas analyses in patients with high cervical cord injuries]. PMID- 4017786 TI - [Changes in urinary hydroxyproline in fractures]. PMID- 4017787 TI - [Humeral fractures complicated by radial nerve injuries: report of 31 cases]. PMID- 4017788 TI - [Treatment of lower urinary tract and pelvic malignancies by the transcatheter chemotherapy of the gluteus inferior artery and by embolization of the internal iliac artery]. PMID- 4017789 TI - [Control of massive non-traumatic urological hemorrhage by transcatheter arterial embolization]. PMID- 4017790 TI - [Anatomy of the pancreatic artery]. PMID- 4017791 TI - [Experimental study on the effect of myelotomy in acute spinal cord injuries]. PMID- 4017792 TI - [Culture of human epidermal cells and preliminary trials on covering wounds]. PMID- 4017793 TI - Differential of light-scattering detection in an arc-lamp-based epi-illumination flow cytometer. AB - Light-scattering histograms of blood cell suspensions were recorded for various ranges of scattering angles by means of an arc-lamp-based flow cytometer (AL FCM). The results were compared with those obtained with a conventional, laser based flow cytometer (L-FCM) with forward scattering (2-20 degrees) and scattering at right angles. Measuring with the AL-FCM in the angle range upward from 13 degrees, the relative light-scattering intensities of lymphocytes, monocytes, and granulocytes were essentially independent of scattering angle and closely similar to the values measured as right-angle scattering in the L-FCM. With a range of scattering angles upward from 2 degrees the AL-FCM yielded histograms similar although not identical to that of the forward-scattering detector in the L-FCM. Differentiation between live and dead cells in this mode of operation was similar in the two instruments. PMID- 4017794 TI - Dual laser flow cytometry: focal length compensation when focussing through a single lens. AB - Dual laser operation of flow cytometers, using a single focussing lens for both beams, requires compensating for chromatic aberration of the lens. By using a prefocussing lens at a fixed position in one of the laser beams, complete focal length compensation is obtained without any loss in system performance. PMID- 4017795 TI - The LLNL high-speed sorter: design features, operational characteristics, and biological utility. AB - This report describes a dual-beam, high-speed sorter (HiSS) with a droplet production rate of 220,000 s-1 now in routine use at the Lawrence Livermore National Laboratory. The system can process and sort objects at rates in excess of 20,000 s-1. We report here on the development of HiSS, describe its operational characteristics, and evaluate its utility for analysis and purification of human chromosomes, human erythrocytes, and living Chinese hamster ovary cells. PMID- 4017796 TI - Automated identification of subpopulations in flow cytometric list mode data using cluster analysis. AB - The application of K-means (ISODATA) cluster analysis to flow cytometric data is described. The results of analyses of flow cytometric data for mixtures of fluorescent microspheres and samples of peripheral blood mononuclear cells are presented. A method for simultaneously displaying list mode data for any number of parameters, which had previously been applied to a continuous set of parameters such as multi-angle light scattering data, is used to present the results of cluster analysis on physically unrelated parameters; this method allows rapid evaluation of the success of subpopulation identification. The factors that influence automated identification of subpopulations are examined, and methods for determining optimal values for these factors are described. PMID- 4017797 TI - Flow cytometric determination of circulating immune complexes with the indirect granulocyte phagocytosis test. AB - A method for the determination of circulating immune complexes (CIC) was adapted for flow cytometric analysis. Human granulocytes were used to phagocytose IgG bearing CIC of serum from systemic lupus erythematosus (SLE) patients. A method for labeling the phagocytosed CIC with FITC-conjugated anti-human IgG was developed where the granulocytes remain in suspension during fixation and labeling. The fluorescence per cell, measured with a flow cytometer, is a measure of the total amount of the phagocytosed IgG. The results indicate that a rapid and quantitative method for the detection and measurement of phagocytosed CIC is possible using the flow cytometer. PMID- 4017798 TI - DNA analysis and sorting of rat testis cells using two-parameter flow cytometry. AB - By use of two-parameter flow cytometry of rat testis cell suspensions stained with mithramycin for DNA (the peak amplitude of the fluorescence signal versus total fluorescence intensity integrated over time), eight cell compartments could be distinguished without pre-enrichment of the samples. Cells in these compartments were identified by sorting and subsequent microscopic examination. PMID- 4017799 TI - Application of DNA flow cytometry to paraffin-embedded archival material for the study of aneuploidy and its clinical significance. AB - By using a recently developed flow cytometric method we have analyzed cellular DNA content of paraffin-embedded histological material from cancer patients. This method allows the retrospective study of tumors from patients whose clinical outcome is already known, and we have applied it to ovarian cancers, stage II breast cancers, and to metastatic adenocarcinoma of unknown primary site. In addition to knowledge of patient survival, comprehensive information was available about other prognostic determinants and treatment received, and we have used multivariate analysis in an attempt to determine the prognostic significance of cellular DNA content. In ovarian cancer, it is a major prognostic variable except in stage IV disease, whereas in metastatic adenocarcinoma of unknown primary site cellular DNA content has no influence on survival. For stage II breast cancer the situation is more complex and requires larger numbers to be studied. However, aneuploid tumors tend to have more extensive involvement of axillary lymph nodes and a poorer overall disease-free survival. This influence of DNA content on disease-free survival appears to be confined to premenopausal patients, and has no effect on patient survival following disease recurrence. Although we need to study more patients and more tumor types, taken together the results so far show a generally more favorable prognosis for patients with diploid tumors, except in the presence of recurrent or metastatic disease. The better prognosis associated with diploid tumors could be due to the fact that they are more commonly found in earlier clinical stages rather than to their being inherently less aggressive than aneuploid tumors. PMID- 4017800 TI - Short-term cryopreservation of human breast carcinoma cells for flow cytometry. AB - A procedure is described for short-term cryopreservation of primary human tumor cells and tissue slices for later analysis by flow cytometry. Cells were mechanically dispersed into a freezing medium, which was then frozen at either 20 degrees C or -70 degrees C for delayed cell cycle analysis. The results show that a correlation coefficient of greater than 0.95 exists between cell cycle kinetic analyses performed immediately after surgical excision of the tumor and on cells frozen from 1 to 30 days at -70 degrees C in this freezing solution. Somewhat lower levels of correlation exist for cells frozen at -20 degrees C in this freezing medium. This procedure has also been successfully used to preserve freshly isolated breast carcinoma cells shipped from distant laboratories for analysis in the flow cytometer, thus expanding the data base on certain types of breast carcinoma. PMID- 4017801 TI - Cell kinetics in normal and neoplastic mammary tissues by flow cytometric analyses. AB - The cell cycle kinetics of normal mammary tissue and cancer mammary tissues were studied by flow cytometry to determine the effect of estrogen and progesterone and antiestrogens on proliferative activity. The proliferative activity was higher in rat mammary tissue during the estrus and pregnant stages compared to the nonestrus or lactational stages. Upon 5 days administration of estrogen and progesterone to the lactating animal, the low proliferative activity was increased to the values found in the pregnant stage. Steroidal effect on proliferative activity was also shown using organ cultures of normal rat tissues and the increase in proliferative activity can be reversed by the addition of 10( 6) M retinoic acid but not by retinyl acetate. In a human mammary tumor cell line (MCF-7), the cell kinetic activity was significantly depressed by antiestrogens (i.e., tamoxifen) as determined by both flow cytometry and tritiated thymidine uptake studies. Finally, a human tumor model system was developed with the MCF-7 cell line in estrogenized nude mice. Flow cytometry of the resulting tumor indicates a tetraploid tumor similar to the cell culture. Cell kinetic analysis of these nude mice tumor cells demonstrates the high proliferative activity of the estrogenized animals compared to the tamoxifen-treated animals. In conclusion, the use of flow cytometry to rapidly measure cell kinetic activity of mammary tissue has been demonstrated. The effects of estrogen or estrogen and progesterone hormones seem to increase the proliferative activity, while antiestrogens decrease this activity. Findings are observed in both in vivo and in vitro conditions or normal tissues, mammary cancer tissue, and cultured cells. PMID- 4017802 TI - Automated analysis and survival selection of anchorage-dependent cells under normal growth conditions. AB - An instrument is described that can automatically analyze and select for a subpopulation of anchorage-dependent cells in tissue culture. Cells that label with fluorescently tagged antibodies or demonstrate structural variations are saved from exposure to a destructive high-intensity argon laser beam. The surviving population may then be cloned. The cell selection may occur in a tissue culture plate or in a microflow incubator which is designed to maintain a constant flow of media at 37 degrees C across cells growing on a glass coverslip. This incubator sits on an inverted microscope which focuses the laser beam to a diameter as small as 1 micron. A high-speed computer-controlled two-dimensional stage moves the cells past the beam for analysis, the results of which determine the fate of each cell: whether it is to be destroyed by radiant energy or selected for survival and subsequent proliferation. Another selection strategy performed by the instrument involves growing the cells on a thin, blackened polyester film which can be cut by the argon laser beam. Cells selected for cloning are then circumscribed. The heat of cutting welds the circumscribed film to a plastic coverslip surface or tissue culture chamber bottom. Nonselected cells may be removed by pulling the unattached polyester sheet from the attachment surface. The selected cells remain on polyester film disks welded to the plastic. Selections may be done automatically under computer control or manually by operator direction of stage movements. This instrument extends the art of automated cell selection and analysis to normal cell lines that must maintain cell-substratum contact (anchorage dependence) for differentiated cell function, e.g., neurons, fibroblasts, or kidney cells. PMID- 4017803 TI - Estimation of nonproliferating cells in the neural retina of embryonic chicks by flow cytometry. AB - Nonproliferating cells (N cells) in the neural retina of embryonic chicks were estimated after isolating them in the 2C peak of a DNA distribution by exposure to the cell-cycle inhibitor ICRF 159. ICRF 159 inhibits cell division but not DNA synthesis, so proliferating cells can leave the 2C peak but not reenter it. Cells left in the 2C peak after exposure to ICRF 159 were assumed to be N cells. The effectiveness of ICRF 159 in inhibiting cell division but not inhibiting DNA synthesis was demonstrated in neural retinae from stage 17 embryos which showed no evidence of a 2C peak after 6-h exposure to ICRF 159 and which were thus shown to have no N cells. A test to detect escape from the cell division block in older embryos with an N cell population in the neural retina showed some escape after longer exposures to ICRF 159. The escape was suppressed by a second dose of ICRF 159, given some hours after the first. PMID- 4017804 TI - Tuning meter can replace oscilloscope for flow cytometer alignment. PMID- 4017805 TI - Active analog pipeline delays for high signal rates in multistation flow cytometers. AB - Flow cytometers with sequential measuring stations require alignment of event timing information to assure that multiparameter data for each cell are properly correlated. Information from the first detector must be delayed until signals are produced at the last detector, with adjustments to align them in time for simultaneous digitization after the last measurement is completed. By using an analog "pipeline" delay, the deadtime between the first and last measuring stations can be minimized. The described device is capable of acquiring and propagating many signals within the delay period, with good fidelity at high signal rates. An integrated circuit charge-coupled device (CCD), which is an analog shift register, is shown to be useful as a signal delay in the time range from 22 microseconds to several milliseconds. PMID- 4017806 TI - Is prophylactic abdominal irrigation with polyvinylpyrrolidone iodine (PVPI) safe? AB - In order to investigate the safety of abdominal irrigation with polyvinylpyrrolidone iodine (PVPI), the abdominal cavities of normal rats were irrigated with the highest nonlethal dose. Samples of the peritoneal fluid were taken before and 1, 2, and 4 hours after irrigations. Control studies were done with saline. After irrigation with PVPI, the protein concentration in the peritoneal fluid showed a 40-fold increase, compared with only a doubling after saline irrigations. Irrigation with PVPI causes serious peritoneal damage, and should therefore not be performed as a prophylactic procedure. PMID- 4017807 TI - A biofragmentable ring for sutureless bowel anastomosis. An experimental study. AB - A biofragmentable bowel anastomosis ring (BAR) for sutureless intestinal anastomosis is described with the laboratory results comparing the BAR to sutured and stapled anastomoses. There was equivalent healing with all three methods of anastomosis. However, "burst" pressure was highest at day zero and overall necrosis was least with the BAR. By virtue of these findings and being sutureless, it is hoped that the limits of safe bowel anastomosis can be extended. PMID- 4017808 TI - Comparison of cleansing methods in preparation for colonic surgery. AB - Golytely, an oral gut lavage solution, was compared with a standard bowel cleansing preparation in patients undergoing elective colonic surgery. Sixty patients were randomly assigned to either a one-day preparation with Golytely and bisacodyl or a standard method using a three-day clear liquid diet, cathartics, and enemas. Colon cleansing was better with Golytely (100 percent optimal cleansing vs. 64 percent, P less than 0.05). Patients receiving Golytely had less weight loss and found this preparation more tolerable. Quantitative stool cultures before and after preparation and intraoperatively were not significantly different between the two preparations. In this surgical bowel preparation study, Golytely and Bisacodyl were found to be safe, rapid, and effective. The preparation was well tolerated by patients and has become our preferred method of colonic cleansing. PMID- 4017809 TI - Mucosal advancement in the treatment of anal fistula. AB - One hundred eighty-nine patients with anal fistula treated within an eight-month to seven-year period by anal fistulectomy and rectal mucosal advancement are presented. An 80 percent follow-up revealed a 90 percent asymptomatic group and a ten percent group who had minor symptoms. Eight percent of the symptomatic patients had minor soiling; 7 percent were incontinent for gas, and 6 percent were incontinent for loose stools. No patient was incontinent for solid feces. There was a 1.5 percent rate of recurrent anal fistula comparable to other techniques. PMID- 4017810 TI - Endoscopy of the terminal ileum. Diagnostic yield in 400 consecutive examinations. AB - A prospective study was undertaken to investigate the feasibility and diagnostic yield of ileoscopy as an extension of total colonoscopy. The distal 15 to 40 cm of the terminal ileum were visualized in 400 of 555 consecutive patients submitted to total colonoscopy (72 percent). Intubation of the terminal ileum was not successful in 42 patients (8 percent), not tried in 63 (11 percent), and hampered by inadequate colonic cleansing in 50 (9 percent). We observed 13 patients with terminal ileitis and seven rare findings such as nonspecific ileal ulcer or non-Meckelian diverticulum, etc., adding to a total of 20 pathologic findings in 400 examinations (5 percent). In a further group of 98 patients, useful diagnostic information was gained by the demonstration of normal ileal findings, making ileoscopy clinically valuable in 118 of 400 examinations (29.5 percent) in this series. We suggest routine endoscopy of the terminal ileum in all patients with suspected or established inflammatory bowel disease and/or persistent diarrhea, lower gastrointestinal tract bleeding, or irritable bowel syndrome, in whom the diagnostic procedure includes colonoscopy. In patients with colorectal tumors or polyps, the diagnostic yield will be unrewarding. PMID- 4017811 TI - Reflux from the continent ileostomy reservoir. A radiologic evaluation combined with pressure recording. AB - The reflux from the continent ileostomy reservoir was studied with radiologic and pressure recording techniques in ten patients. The contrast used was poly-iodine styrene with a density of 0.8 to 1.1 gm/cm3. Reflux into the afferent loop was demonstrated in all patients at a filling volume of approximately 30 percent of the maximal volume capacity of the reservoir. The magnitude of reflux increased with the increasing volume of the reservoir contents and a rise in reservoir pressure. The reflux could temporarily be influenced by antiperistaltic or isoperistaltic motor activity in the afferent loop. Although no adverse effects were seen from the amount of reflux demonstrated in the present investigation, the finding of increasing reflux with increased fullness and intraluminal pressure of the reservoir would indicate that the reservoir should be emptied at regular intervals and before high pressures are built up. PMID- 4017812 TI - A reconstructive operation on malfunctioning S-shaped pelvic reservoirs. AB - Patients with triple-loop pelvic reservoirs have often suffered from evacuation problems, clinically shown as the need for intubation, frequent stooling, leakage or ileoanal disruptions. In a recent study, the authors have shown that malposition of the reservoir and presence of a long, kinked, efferent limb constitute the main causes of these problems. A corrective operation consequently was designed in order to improve pouch topography. The pouch and its efferent conduit were completely mobilized and the efferent limb was shortened considerably. The reservoir then was placed in close proximity to the anus and the ileoanal anastomosis was reestablished. This operation now has been performed in seven patients who were considered "failures" and the results are gratifying. Six of these patients now have efficient evacuation and four are completely without leakage. Comparison of pre- and postoperative clinical and radiologic variables confirm the strong correlation between reservoir topography and clinical outcome. PMID- 4017813 TI - Strictureplasty in diffuse Crohn's jejunoileitis. AB - Strictureplasty recently has been advocated in the treatment of obstructive strictures of the small bowel in patients with Crohn's disease. In contrast to conventional methods of treatment, such as conservative therapy with total parenteral nutrition (TPN) or surgical resection of the involved bowel, strictureplasty eliminates the obstruction without loss of small bowel. The possibility of creating a short-bowel syndrome is of special concern in patients with diffuse Crohn's jejunoileitis. These patients usually present for surgery with chronic obstruction, anemia, weight loss, and malnutrition with folate and other vitamin deficiencies. The authors report the results of 12 strictureplasties for extensive Crohn's jejunoileitis in three patients presenting with chronic obstruction secondary to multiple small-bowel strictures. Both Heineke-Mikulicz and Finney strictureplasties were performed. In two patients, resection of an acutely inflamed phlegmonous segment was also performed. Symptoms (pain, abdominal distention, and nausea) were markedly improved postoperatively in all patients. Nutritional parameters, including serum albumin and total lymphocyte count, improved postoperatively. Dramatic rises in weight were noted also. All three patients were symptom-free six months postoperatively. PMID- 4017814 TI - Gangrene of male external genitalia in a patient with colorectal disease. Anatomic pathways of spread. AB - This is the report of a patient with gangrene of the skin and subcutaneous tissue of the scrotum and base of the penis secondary to diverticulitis of the sigmoid colon. Due to high mortality in such patients, the early, rapid, and radical debridement of all devitalized tissues and prompt recognition of the source of sepsis is of utmost importance. Computed tomography (CT) scanning facilitates delineating the extent of disease. Anatomy of the perineal body and pathways of spread are discussed. PMID- 4017815 TI - Subcutaneous metastases without visceral metastases from an adenocarcinoma of the rectum. AB - Skin metastasis from colorectal carcinoma without evidence of visceral metastases is exceedingly rare. However, it must be considered whenever a new skin growth appears in a patient with a history of carcinoma. A diagnostic biopsy is mandatory as the appearance of these metastases is not distinctive. PMID- 4017816 TI - Enterocutaneous fistulization due to Actinomyces odontolyticus. Report of a case. AB - A case of abdominal actinomycosis originating from the sigmoid colon is presented. Actinomyces odontolyticus was isolated; it is a rarity, but should be suspected in the case of a palpable mass and several fistulas developing after a latent period of weeks to months following surgical or inflammatory trauma. The diagnosis is made by anaerobic cultivation. Primary treatment with large doses of penicillin for several weeks may be supplemented by surgery. The strain isolated in the present case was only moderately sensitive to penicillin and was successfully treated with erythromycin. PMID- 4017817 TI - The surgical management of Crohn's disease of the terminal ileum. PMID- 4017818 TI - Internal fistulas in Crohn's disease. AB - There is doubt about the timing of surgery for patients with internal fistulas in Crohn's disease. Although immediate operative intervention for all patients has been advocated, such a policy has not always been followed at St. Mark's Hospital. Between 1971 and 1982, 83 internal fistulas were identified in 59 patients with Crohn's disease. Fifty-nine fistulas arose primarily from the small intestine and involved another segment of the bowel, five were between large bowel and duodenum, and three between areas of large bowel. Sixteen fistulas (ten from ileum and six from large bowel) involved the bladder. Thirty-six patients with 54 fistulas underwent immediate surgical treatment. Fifteen patients with 20 fistulas required surgery later. There was one postoperative death among the 51 patients treated surgically and one late death unrelated to the treatment of the fistula. Of the remaining 49 surgically treated patients, 46 were traced and remain well, six after further surgery. Eight patients with nine fistulas (four involving the bladder) were treated at St. Mark's without operation. One later required surgery elsewhere for an enterocutaneous fistula, but the remaining seven patients are well. This study suggests that the presence of an internal fistula, even if it involves the bladder, is not an absolute indication for immediate surgery and that the severity of the symptoms should dictate the treatment policy. PMID- 4017819 TI - Surgical resection of pulmonary metastases from colorectal adenocarcinoma. AB - From 1962 to 1982, 27 patients with pulmonary metastases as the only site of recurrent colorectal carcinoma underwent pulmonary resection at Roswell Park Memorial Institute. Only five of these patients had symptomatic pulmonary lesions. No postoperative mortality occurred. The median survival after pulmonary resection was 27 months. Five patients are alive presently without recurrent colorectal cancer and two patients are alive with recurrent pulmonary metastases. Patients with solitary lesions had a better survival than patients with multiple lesions. The major sites of recurrence following thoracotomy were the lungs and liver. PMID- 4017820 TI - Transanal rectovaginal fistula repair. AB - In this update, 15 additional successful transanal repairs followed for one to six years postoperatively for low rectovaginal fistulas without colostomies are added to the uniformly successful 20 patients presented in a 1978 report. Changes in perioperative routines have greatly enhanced cost efficiency and these modifications are enumerated. The repair still encompasses total excision of the epithelialized fistula, and reapproximation of the attenuated septal fibers and anal sphincter mechanism, as well as the caudad rectal mucosal advancement that covers and protects the repair from the fecal stream and the high intraluminal pressures of defecation. Once again, we have excluded inflammatory, neoplastic, and irradiation-caused fistulas from this discussion, although we, as well as others, have applied this technique in selected cases. PMID- 4017821 TI - Rectal prolapse and anal incontinence treated with a modified Roscoe Graham operation. AB - The results of abdominal mobilization of the rectum and repair of the pelvic floor behind the anorectal junction are reported in 23 patients with rectal prolapse, being accompanied by some form of anal incontinence in 12. Within 20 months, on the average, three patients had recurrent prolapse. Two thirds of the patients with incontinence for solid and/or fluid feces were cured for prolapse as well as incontinence. Seven became constipated, while 14 were fully satisfied. Seven of eight patients with a highly reduced tone of the external sphincter before surgery had a marked improvement after surgery. The results do not differ greatly from those after the suspension operation or repair of the pelvic floor in front of the rectum, despite being more physiologic, but suggest that simultaneous suspension and abdominal repair of the pelvic floor may avoid the need for a secondary postanal repair from below in patients with persistent incontinence after suspension surgery. A controlled, randomized trial is advocated. PMID- 4017822 TI - Relationship of symptom duration and survival in patients with carcinoma of the colon and rectum. AB - The generally held belief that early diagnosis and treatment are associated with a greater proportion of localized tumors and better prospects of salvage is not supported in carcinoma of the large intestine. This study is not to be interpreted to mean that purposefully delayed treatment in an individual patient will improve his chances of survival. Its purpose is to place the emphasis on early diagnosis in its proper perspective. Entirely different methods of diagnosis need to be developed so as to be able to diagnose carcinoma of the large intestine during its presymptomatic phase. PMID- 4017823 TI - Volvulus of the splenic flexure of the colon. AB - Volvulus of the splenic flexure is a rare cause of large-bowel obstruction. Three cases are presented and the features of 17 previously reported cases reviewed. Resection with or without primary anastomosis is the procedure of choice to prevent recurrence. PMID- 4017824 TI - Sphincter-saving procedure for treatment of diffuse cavernous hemangioma of the rectum and sigmoid colon. AB - Two cases of diffuse cavernous hemangioma of the rectum and rectosigmoid colon are reported. Sphincter-saving procedures were applied as the surgical treatment for these two patients. The diseased rectum and distal sigmoid colon were resected 3 cm above the pectinate line. The mucosa of the rectal stump was extirpated. All visible residue from the hemangiomatous tissues on the muscular cuff, pararectal space, and pelvic wall were denuded. The normal colon was then pulled down through the rectal cuff and anastomosed with anoderm, and attached to the internal sphincter muscle. Both patients recovered uneventfully. No uncontrollable hemorrhage was encountered during rectal dissection. Both patients had good anal sensation and perfect continence. No complicated sexual or urinary disturbances were found. The sphincter-saving procedure for treatment of diffuse cavernous hemangioma of the rectum should be promoted and given first choice whenever possible. PMID- 4017825 TI - Acute suppurative appendicitis. A rare associate of Crohn's disease. AB - A case is presented of acute suppurative appendicitis occurring with Crohn's disease. The association is rare (only five other cases described), but if diagnostic uncertainty exists, laparotomy should be performed early. If, at laparotomy for suspected appendicitis, Crohn's terminal ileitis is incidentally found, the appendix should be removed. PMID- 4017826 TI - Eosinophilic colitis. AB - Eosinophilic gastroenteritis, a condition of unknown etiology, has frequently been reported involving the stomach and small bowel. The colon is rarely cited as a site for the condition; however, a review of the literature reveals over 20 cases (including ours). The findings indicate that the colon is now a recognized, but rare, site of involvement and that the condition can be diagnosed via the colonoscope. No clear-cut etiology can be defined, but the presence of allergy (33 percent) and of the herring worm (two cases) is noted. PMID- 4017827 TI - Synchronous lesion of the colon. PMID- 4017828 TI - On the treatment of hemangioma of the rectum. PMID- 4017829 TI - Value of computed tomography in the detection of complications of Crohn's disease. AB - Abdominal and pelvic computed tomography (CT) scans were performed on 17 patients with suspected complications of Crohn's disease. CT was superior to conventional barium studies and colonoscopy in demonstrating mural, serosal, and mesenteric pathology such as bowel wall thickening (100%), abscess (59%) and phlegmon (6%) formation, and fibro-fatty proliferation of the mesentery (41%). While not advocated as the primary means of evaluating Crohn's disease, CT can provide information vital to the management of complications of this disease. PMID- 4017830 TI - Effect of nifedipine on gastric emptying in normal subjects. AB - We studied the effects of the calcium-channel blocker, nifedipine, on solid and liquid phases of gastric emptying in 10 healthy male volunteers. Each subject underwent a dual-isotope radionuclide gastric emptying determination with and without the preadministration of nifedipine, 30 mg orally, given 20 min prior to ingestion of the test meal over 10 min, following which the subject lay supine under the gamma-counter for 2 hr. Blood samples for measurement of plasma nifedipine concentration were obtained at the time of drug administration and every 30 min throughout the gastric emptying determination. There was a threefold variation in the areas under the plasma nifedipine concentration vs time curve (AUC) obtained in these 10 subjects. Percent gastric retention of either the liquid (water) or the solid (chicken liver) marker was not significantly different after 30 mg oral nifedipine, as compared to the nontreatment day. We concluded that plasma nifedipine concentrations previously reported to be associated with significant esophageal motility effects in humans were not associated with effects on gastric emptying of either liquids or solids. PMID- 4017831 TI - Definition of a gastric emptying abnormality in patients with anorexia nervosa. AB - Upper gastrointestinal symptoms may be prominent in anorexia nervosa. This study is an investigation of the gastric emptying of solid and liquid meal components in 16 female patients (mean age 20.0 years, range 14-40 years) who met accepted psychiatric diagnostic criteria for anorexia nervosa. The results were compared with those of gastric emptying studies in 10 normal females of ideal body weight (mean age 25.4 years, range 20-35), 13 normal persons (12 males), and six patients (mean age 12 years, range 9-14 years) with weight loss (less than 90 percent ideal body weight) secondary to Crohn's disease with no psychiatric symptoms. A dual-isotope technique using chicken liver intracellularly labeled with technetium-99m (99mTc) bound to sulfur colloid as the solid-phase marker, and indium-111 (111In) -labeled water as the liquid-phase marker was used. Gastric emptying was monitored for 2 hr by gamma camera. In 13 of the 16 anorexia nervosa patients (80%), gastric emptying of solids was slower than the range in the two groups of normal subjects, and mean gastric emptying was significantly slower (P less than 0.05) than in the weight-loss patients. Liquid emptying (water) in anorexia nervosa was normal and similar to the control groups studied. In 11 of the anorexia nervosa patients with delayed gastric emptying, intramuscular metoclopramide, 10 mg, significantly (P less than 0.05) accelerated the mean gastric emptying from 60 through 120 min after the meal. We conclude that in anorexia nervosa patients who are symptomatic and seeking medical care: gastric emptying of solids is significantly delayed when compared with female subjects of similar age and normal body weight and with patients of less than 90% ideal body weight but without psychiatric disorder; these data are consistent with an antral motility disturbance, either primary or secondary; and metoclopramide, a gastric prokinetic agent, accelerates (delayed) gastric emptying. PMID- 4017833 TI - Dissociation of duodenogastric marker reflux and bile salt reflux. AB - Duodenogastric reflux of a perfused marker and bile salt reflux, as well as emptying of fasting gastric contents and gastric secretion, were measured simultaneously in six healthy volunteers. Each of the subjects was studied three times in randomized order during intravenous administration of either saline or atropine (40 micrograms/kg/4 hr) or cerulein (360 ng/kg/4 hr). Fractional gastric emptying rate was inhibited from 4.57%/min +/- 0.50 SE to 0.70 +/- 0.15 by atropine (P less than 0.001) and to 1.80 +/- 0.29 by cerulein (P less than 0.005). Atropine increased reflux of duodenally perfused phenol red from 0.95 +/- 0.28 to 26.09 +/- 4.98% (P less than 0.005) without affecting bile salt reflux (0.44 +/- 0.07 vs 0.51 +/- 0.17 mumol/min). In contrast, cerulein did not significantly affect duodenogastric marker reflux (2.23 +/- 0.82%) but increased bile salt reflux to 0.94 +/- 0.16 mumol/min (P less than 0.05). It is concluded that reflux of duodenal contents and reflux of bile salts do not necessarily parallel each other. This may produce considerable confusion by apparently contradictory results in studies on duodenogastric reflux. PMID- 4017835 TI - Abstracts of papers presented at the Tenth International Symposium on Gastrointestinal Motility. September 8-11, 1985. Rochester, Minnesota. PMID- 4017832 TI - Evaluation of Angelchik antireflux prosthesis. Long-term results. AB - Fifteen patients with intractable reflux or its complications were sequentially studied after the placement of the Angelchik antireflux prosthesis. In all, 16 devices were inserted. Parameters were measured before and 3, 12, 24, and 36 months after prosthesis placement and included symptom scoring, esophageal manometry with Tuttle test, endoscopy, suction biopsy, barium swallow, and gastroesophageal scintigraphy. In addition, a subset of patients underwent stimulation/inhibition of the lower esophageal sphincter (LES) with pentagastrin, metoclopramide, edrophonium, and atropine. At a mean time of 16 months postsurgery, 10 of 16 (63%) patients were reflux-free and there was significant improvement in endoscopic, biopsy, and symptom scoring. Post-insertion, there were statistically significant increments in LES pressure with intravenous boluses of pentagastrin, metoclopramide, and edrophonium, and a significant decrease with atropine. Two patients who developed prosthesis herniation into the chest required removal because of ongoing reflux and dysphagia. An additional patient had prosthesis disruption and migration, which also required removal. Four patients with previously failed antireflux procedures had five prostheses placed. All continued to reflux postoperatively. No patient who was initially reflux-free subsequently developed reflux, despite a tendency for LES pressure to decline with time. Although this procedure proved effective for up to 36 months in patients who had had no previous antireflux procedure, the displacement rate (3/16 = 19%), reoperation rate (3/16 = 19%), and the progressive decline in LES pressure over time should make one cautious about its routine use in the surgical treatment of reflux esophagitis. PMID- 4017834 TI - Origin and characterization of migrating myoelectric complex in rabbits. AB - Myoelectric activity patterns of the upper gastrointestinal tract were recorded using chronically implanted electrodes in conscious rabbits. A cyclical pattern of intense spiking activity occurring on almost every slow wave for 10-15 min, corresponding to the regular spiking phase or phase III of the migrating myoelectric complex (MMC), was recorded. This activity was detected by electrodes implanted distal to the ligament of Treitz on the proximal jejunum at a frequency of 9.4-10.6/24 hr. The MMC pattern occurred in both fed and fasted animals, regardless of the presence of cecotrophy. Initiation of phase III activity on the jejunum persisted after transplantation of the pancreatic duct opening to the proximal duodenum 5 cm from the pylorus and when gastric contents emptied directly into the proximal jejunum through a large gastrojejunostomy. It is concluded that the MMC pattern of the rabbit small intestine is persistently initiated in the proximal jejunum distal to the pancreatic and biliary ducts. The jejunal origin of the MMC in the rabbit is reminiscent of that seen transiently 8 10 hr after a meal in dogs during the change from fed to the fasted pattern of gastrointestinal motor activity. PMID- 4017836 TI - Splenic abscess. A rare complication of Crohn's colitis. AB - This report describes a patient with Crohn's disease of the colon who presented with a rare extraintestinal complication: splenic abscess. Additional features of this case were the association of multiple extraintestinal manifestations of Crohn's disease, including iritis, ankylosing spondylitis, and pericholangitis, and polymicrobial bacteremia. This report emphasizes the cryptic nature of splenic abscess presentation, the more frequent association of extraintestinal manifestations of Crohn's disease with intraabdominal complications, and the association of polymicrobial anaerobic bacteremia with obstructive gastrointestinal complications. PMID- 4017837 TI - Serum trypsin-like immunoreactivity and steatorrhea. PMID- 4017838 TI - Spermine as a gastric antisecretory agent. PMID- 4017839 TI - [Studies on the genetic and environmental epidemiology of esophageal cancer in seven families in Linxian County]. PMID- 4017840 TI - [Effect of riboflavin deficiency and massive doses of vitamin C on carcinogenesis in the esophagus and liver in rats]. PMID- 4017841 TI - [Preliminary investigation of the esophageal epithelial cells in members of families with high and low incidence of esophageal cancer]. PMID- 4017842 TI - [Trace elements in hair, serum and cancerous tissue in patients with esophageal cancer]. PMID- 4017843 TI - [Study of premature chromosome condensation (PCC) II. X-ray effect on PCC damage of HeLa cell and progress of the cell cycle]. PMID- 4017844 TI - [Study on the tumor-associated transplantation antigen (TATA) of L615 mouse leukemia cells (L615 cells)]. PMID- 4017845 TI - [Radiologic manifestations of the mediastinal type of bronchogenic carcinoma]. PMID- 4017846 TI - [Clinicopathologic analysis of giant cell tumor of the bone--report of 35 cases]. PMID- 4017847 TI - [Combined preoperative 60Co radiation and surgery for middle-third esophageal carcinoma--an analysis of 323 cases]. PMID- 4017848 TI - [Multiple myeloma--an analysis of 42 cases and review of the Chinese medical literature on 522 cases]. PMID- 4017849 TI - [Clinical study of 16 cases of inflammatory pseudotumor in the lung]. PMID- 4017850 TI - [Nipple discharge]. PMID- 4017851 TI - [Hemangiopericytoma--report of 13 cases]. PMID- 4017852 TI - [Diagnosis of malignant giant cell tumor of the soft tissue--report of two cases]. PMID- 4017853 TI - [Ultrastructural characteristics of lipid absorption]. PMID- 4017854 TI - [Tissue correlates in the autotransplantation of skeletal muscle tissue into the brain of rats]. PMID- 4017855 TI - [Mechanics of the excited nerve fiber]. PMID- 4017856 TI - [Marker stability in the electron microscopic visualization of cytosine]. PMID- 4017857 TI - [Phospholipases of the nuclear structures of liver cells in white rats]. PMID- 4017858 TI - [Neuronal impulse activity of the striopallidum in the monkey during postponed behavior]. PMID- 4017859 TI - [Hypotensive activity of the nitrosyl complexes of nonheme iron with different anionic ligands]. PMID- 4017860 TI - [Mechanisms of the stabilization of PO2 in the blood in muscle microvessels]. PMID- 4017861 TI - [Sensitivity and precision of the operation of the human physiological thermostat]. PMID- 4017862 TI - [Spinal interneurons activated by bilateral afferent and cortical influences]. PMID- 4017863 TI - [Analysis and evaluation of the potential of human voice]. PMID- 4017864 TI - [Interaction of xenobiotics and serum albumin as a specialized evolutionally conditioned protective mechanism]. PMID- 4017865 TI - [Characteristics of the effect of thrombin on macromolecular substrates]. PMID- 4017866 TI - Effects of cigarette rod length on puff volume and carbon monoxide delivery in cigarette smokers. AB - As part of a continuing series of studies to investigate the variables controlling various topographical aspects of cigarette smoking, the present study examined the extent to which cigarette rod length influenced smoking. Cigarette smoking was examined under conditions in which subjects smoked cigarettes they could not see. Both puff volume and puff duration varied as a direct function of rod length, although they were not highly correlated. Peak flow rate was not affected by rod length. Other results suggest that visual stimulus control and satiation did not affect puff volume. Comparison of puffing whole cigarettes versus short cigarette rods suggests that puff volume, but not puff duration, may be decreased in response to increased pharmacological delivery as a result of particulate build-up during smoking of a whole cigarette. Carbon monoxide (CO) exposure was substantially greater after puffing full length cigarette rods than after short cigarette rods. Comparison of these human CO data with CO delivery from syringe-simulated puffing of full length and short cigarette rods indicates that knowledge of puff volume and duration during human smoking is insufficient for accurately predicting biological (CO) exposure. PMID- 4017867 TI - Alcohol use and trait anxiety in the general population. AB - The relationship between alcohol consumption and trait anxiety in a large sample representative of the U.S. general population was examined. Sex, age and ethnicity were used as control variables. It was found that men consumed more alcohol than women, and that this difference was largest for Catholic ethnic groups. For most groups of respondents, there was little or no relationship between trait anxiety and alcohol consumption. Among young and middle-aged males from Catholic ethnic groups, however, those with more anxious personalities drank more. PMID- 4017868 TI - Differentiation of alcoholics high and low in childhood hyperactivity. AB - Fifty alcoholics who reported a greater number of childhood hyperactivity/minimum brain damage (MBD) symptoms (HA+ alcoholics) were compared to 49 alcoholics low in childhood hyperactivity/MBD (HA- alcoholics) with respect to patterns and severity of alcoholism, psychosocial functioning and physical status, personality and psychopathology, and familial alcoholism. HA+ alcoholics were found to report considerably more psychopathology on the MMPI and the Psychopathic State Inventory (PSI), findings which were suggestive of an underlying personality disorder. HA+ alcoholics were also found to differ significantly from the HA- alcoholics in several areas of psychosocial functioning and with respect to their pattern of alcoholism. That is, HA+ alcoholics had more interpersonal difficulties and had experienced more psychological/emotional problems; they were more likely to use alcohol to alter their moods and to use non-alcoholic illicit drugs; and they had less ability to internalize control of their impulses to consume alcohol. These findings, taken together, suggest that alcoholics reporting more symptoms of childhood hyperactivity/MBD may represent a subgroup within the larger alcoholic population. High and low hyperactivity alcoholics did not differ in severity of alcoholism or in alcohol-related physical effects or medical problems. Additionally, no evidence was obtained for a significant relationship between childhood hyperactivity and familial alcoholism. PMID- 4017869 TI - Comparison of fixed-ratio and progressive-ratio schedules of maintenance of stimulant drug-reinforced responding. AB - The effectiveness of doses of i.v. cocaine and nomifensine in maintaining lever press responding in rhesus monkeys was evaluated under two schedules, fixed- and progressive-ratio (FR, PR). The doses that maintained maximum rates of responding under the fixed-ratio schedule were 0.32 mg/kg per injection cocaine and 0.10 mg/kg per injection nomifensine. The fixed-ratio rates maintained by this dose of nomifensine were slightly lower than those maintained by cocaine. Under the progressive-ratio schedule, the maximum response rates developed with 0.32 mg/kg per injection cocaine and 0.32 mg/kg per injection nomifensine. Maximum performances under the progressive ratio were slightly higher with cocaine than with nomifensine. Taken in conjunction with existing data for other drugs and conditions, these data indicate that progressive-ratio schedules may yield information on the relative reinforcing effects of drugs that differs only slightly from that obtained with fixed-ratio schedules. PMID- 4017870 TI - Drug dependence units in England and Wales. The results of a national survey. AB - Drug dependence units (DDUs) form the cornerstone of government policy response to problem drug taking. Yet we know surprisingly little about the facilities that they can provide and what treatment policies they adopt. This paper constitutes a modest attempt to fill some of the gaps in our knowledge and points to the need to base future policy recommendations on detailed empirical research. PMID- 4017871 TI - Depressive symptoms differentiating between heroin addicts and alcoholics. AB - The Beck Depression Inventory (BDI) was self-administered to 105 outpatient alcoholics and 211 methadone maintenance patients seeking treatment at a large community mental health center to determine whether or not specific depressive symptoms differentiated the groups. Canonical correlations were first calculated between the set of 21 BDI items and the patients' demographic characteristics of sex, race and age to ascertain if these characteristics should be controlled before making comparisons between the two types of substance abusers. Age and sex were significantly related to self-reported depressive symptomatology and were entered first into a stepwise discriminant analysis with the 21 BDI items followed by type of substance abuse. Four symptoms contributed at least 5% to the overall discrimination between the alcoholics and the heroin addicts; these were sense of failure, weight loss, somatic preoccupation, and loss of libido. The alcoholics described themselves as feeling more like failures and having more somatic preoccupation than the heroin addicts, whereas the heroin addicts reported more weight loss and loss of libido. To estimate the efficiency with which these four symptoms could differentiate between the alcoholics and heroin addicts, discriminant classification analysis was employed; 69.3% of the substance abusers were correctly assigned to their type of addiction. The results were discussed as supporting the contention that alcoholics and heroin addicts may display different depressive symptoms. PMID- 4017872 TI - A comparative analysis of two methods for the study of alcohol intake in Mexico. AB - Two different methodologies were studied in a semi-rural community in Mexico city to investigate alcohol-intake patterns and attitudes towards drinking and drunkenness. One of the methods consisted of a household survey. The other used the anthropological informant's technique. These methods were compared only at those points where were found similarities in the data collected. We conclude that both methods give comparable estimates of what goes on in the community. Nevertheless the informant method is cheaper, results are obtained in less time and the community members are engaged in this problem, thus permitting future action to be taken. PMID- 4017874 TI - Paradigm shift or change in ownership? The conceptual significance of D.L. Davies's classic paper. AB - D.L. Davies's paper on 'Normal drinking in recovered alcohol addicts' was published in 1962 (Q.J. Stud. Alcohol, 23, (1962) 94). The 18 commentaries on this report which were published shortly afterwards in the Quarterly Journal of Studies on Alcohol are analysed in terms of the perceived relevance of his findings for clinical practice. This initial and largely negative appraisal of the import of Davies's article is contrasted with later assessments which have seen this study as contributing to a crucial paradigm shift. The question is raised as to whether the concept of paradigm shift can be applied satisfactorily to a field where several different scientific disciplines are defining the nature of the problem, or whether alternatively or in addition the story should be understood in terms of a competition between medicine and psychology for 'ownership' of addiction. PMID- 4017873 TI - A comparison of young drinking offenders with other adolescents. AB - Interviews with 104 youths convicted of an underage alcohol offence (young drinking offenders), 30 youths convicted of an offence not involving alcohol (delinquents) and 31 youths with no convictions (comparison group) were conducted. Young drinking offenders and delinquents differed from the comparison group, but not each other, on measures of attitude, drinking behaviour and problems, other drug use and previous criminal activities. However, the young drinking offenders did differ from the delinquents on measures of social environment. The high levels of alcohol consumption and alcohol problems reported by the young drinking offenders and delinquents reveal large numbers of problem drinkers in these two groups. It is proposed that the deviant behaviour displayed by these two groups may be a result of similar underlying processes, which can be modified by social environment factors. PMID- 4017875 TI - The non-medical use of prescription psychotropic drugs by school boys in greater Cairo. AB - Data, previously collected in the context of a large-scale study of the extent of substance use among male Egyptian secondary and technical school students, were broken down along a parameter of use/non-use of prescription psychoactive drugs. Users were compared with non-users on five clusters of queries included in a standardized questionnaire, relating to: family ties, participation in peers' activities, exposure to drug-related stimuli, boldness and health problems. Users were found to report weak family ties, persistent participation in peers' activities and consistent exposure to drug-related stimuli. They were daring in relating to the drug universe and were less healthy (physically and psychologically) than non-users. These findings are discussed in the light of relevant previously reported results of epidemiological studies. PMID- 4017876 TI - Epidemiology of liver cirrhosis morbidity and mortality in Western Australia, 1971-82: some preliminary findings. AB - Liver cirrhosis mortality and morbidity (primary and secondary diagnosis) data for Western Australian men and women over the age of 30 years for the period 1971 82 are presented. Correlations between the morbidity and mortality data and adult consumption of beer, wine, spirits and absolute alcohol are also reported. Possible reasons for the various significant correlations are discussed, and in particular, with respect to the increasing wine consumption of adults (greater than or equal to 15 years). PMID- 4017877 TI - The association between tobacco smoking and use of other psychoactive substances among Egyptian male students. AB - The present study is part of a large scale project on the extent of substance use among young people in Egypt. Data collected on two representative samples of secondary school boys (N = 5530) and technical school pupils (N = 3686) through the administration of a standardized questionnaire are broken down along four parameters: tobacco smoking, use of medical psychoactive substances, consumption of natural narcotics and alcohol drinking. In the present paper we concentrate on relevant answers of tobacco smokers vs. non-smokers in both secondary school and technical school students. More smokers than non-smokers were found to be living away from their families and stating that at least one of the parents was dead. More smokers than non-smokers reported participating in peers' activities. Smokers were, also, found to outnumber non-smokers in being exposed to various kinds of drug-use related stimuli. Invariably, tobacco smokers were found to be more daring than non-smokers in thinking of psychoactive substances, in trying such substances and in continuing to take them. Smokers were, moreover, reported to exceed non-smokers in being under treatment from various physical as well as psychological ailments. These findings were discussed with emphasis on their heuristic value for the development of plans for treatment and/or prevention. PMID- 4017878 TI - Alterations in catecholamine metabolism partially corrected during amphetamine dependence. AB - A woman appeared to clinically benefit from high doses of amphetamine taken for a period of 27 years. During amphetamine administration, elevated urinary 3-methoxy 4-hydroxy-phenylglycol (MHPCG) excretion values returned to normal accompanied by reductions in plasma phenylalanine. PMID- 4017879 TI - Reliability of a family tree questionnaire for assessing family history of alcohol problems. AB - The test-retest reliability of a brief, easily administered questionnaire to assess family history of drinking problems was studied. Twenty alcoholic and twenty non-alcoholic volunteers completed the questionnaire on each of two occasions separated by about 2 weeks. The reliability of classification of first- and second-degree relatives as problem drinkers or alcoholics was examined, using both liberal and conservative diagnostic criteria. In general, both sets of criteria produced satisfactory test-retest reliability; one possible exception occurred when alcoholics' second-degree relatives were classified using the conservative criteria. The liberal criteria seemed to provide a more sensitive index of familial alcoholism. PMID- 4017880 TI - Treatment of chronic cocaine abuse and attention deficit disorder, residual type, with magnesium pemoline. AB - Research suggests that attention deficit disorder (ADD) may persist into adulthood, perhaps predisposing certain individuals to stimulant abuse. The authors describe two adults with chronic cocaine abuse and apparent residual ADD. After failing to respond to conventional treatment modalities, these patients were administered magnesium pemoline. Both displayed a sustained reduction in their cocaine use, without abusing pemoline. This finding suggests that the diagnostic assessment of cocaine abusers should include a search for a history of ADD. A carefully selected subgroup of this population may benefit from treatment with other stimulant medications. PMID- 4017881 TI - Oxidative capacity and ethanol. An in vivo study on hepatocytes and some brain regions of the female rat. AB - The effect of ethanol on respiratory coefficients in the isolated hepatocytes and on oxygen consumption by slices of brain regions were studied. Ethanol inhibits carbon dioxide production and the respiratory quotient in most of the assayed cases. However, oxygen consumption is apparently unaffected. When the hepatocytes were incubated for 1 h with doses of 10, 20, 40, 80 and 100 mM ethanol, the cellular viability decreased by 27, 33, 34, 48 and 67%, respectively. The effects on respiration are discussed in relation to the cellular viability. The results indicate that ethanol inhibits oxygen consumption in the hypothalamus and hippocampus. However, in the amygdala no significant differences were observed. In the cortex, a byphasic effect was observed. PMID- 4017882 TI - Two versions of dependence: D.S.M.-III and the alcohol Dependence Syndrome. AB - This paper reviews the concepts of dependence on alcohol as embodied by the Alcohol Dependence Syndrome and as proposed in the Diagnostic and Statistical Manual of the American Psychiatric Association (D.S.M.-III). Evidence in support of the unidimensionality of this concept is still controversial, and the elements necessary to diagnose dependence under each of these two proposals are different. Alcohol Dependence in the D.S.M.-III has indicators of social and occupational impairment which are not part of the Alcohol Dependence Syndrome. Knowledge on the concept of dependence will advance more rapidly if researchers begin to develop comparative studies of these two models. Future work should also include studies in the general population, with women, ethnic minorities and cross cultural research. Longitudinal research to establish the evolution of dependence both in clinical and general populations should also be developed. PMID- 4017883 TI - Prophylaxis for endocarditis. PMID- 4017884 TI - [Risk of transmission of hepatitis through human fibrin adhesives]. AB - A prospective study of the incidence of post-operative hepatitis was carried out in 417 patients following open-heart surgery. During the observation period 16 (3.8%) patients contracted hepatitis (15 non-A, non-B hepatitis; 1 hepatitis B). Fibrin seal was used intraoperatively in 19 patients; post-operatively there was no evidence of hepatitis in any of these cases. Thus fibrin seal should not be grouped with "high hepatitis-risk" preparations. PMID- 4017885 TI - [Physician's counseling in conflict about pregnancy. Dilemma and chance]. PMID- 4017886 TI - [Cystic liver with acute hemorrhage]. PMID- 4017887 TI - [Manifestations of progressive paralysis. Not a theme of the past]. AB - Investigations carried out on 293 cases of progressive paralysis showed that the widely held view of a "classical form" of progressive paralysis is not applicable. Thus megalomania was found in only 13% of the patients and a manic type state in less than half. Disturbances in affectivity, drive and intellectual functions in progressive paralysis are, in general, uncharacteristic and can appear in any psychotic syndrome. Moreover, neurological symptoms taken as characteristic for progressive paralysis such as the Argyll-Robertson phenomenon or the "mimic quivering" are more the exception than the rule. PMID- 4017888 TI - [Size of cell nuclei in non-Hodgkin lymphomas. Prognostic and diagnostic significance]. AB - Morphometric analysis of cell-nucleus size was undertaken in 300 cases of malignant non-Hodgkin lymphomas. The results were compared with histological findings and survival time. It was found that the histological lymphoma groups differ significantly only occasionally with regard to nucleus size. Within the groups the values have such wide scatter that in the individual case it is not possible to assign it on morphometric data. This scatter mirrors the difficulties encountered in histological classification which - as the objective data indicate - are due to numerous transitions between different types of lymphoma. Analysis of survival data shows that nucleus size is of considerable prognostic value, if certain exceptions such as lymphoblastic lymphoma are taken into account. The results favour tripartite division of malignant lymphomas for prognostic purposes. PMID- 4017889 TI - [Successful therapy of recurrent hypoglycemias by surgical removal of a malignant hemangiopericytoma]. AB - Tumor growth in a 72-year-old male patient with malignant haemangiopericytoma in the left hemithorax could be followed radiologically for 4 years before symptoms of recurrent hypoglycaemia appeared. The endogenous insulin level in serum was maximally and serum IGF-1 and IGF-2 markedly reduced. An intravenous arginine load test showed a normal stimulation capacity of the pancreatic glucagon secretion but not that of insulin. After resection of the tumor, blood sugar metabolism was completely normalised. The insulin level, IGF-1 and IGF-2 in serum returned to normal. PMID- 4017891 TI - [Hemiparkinson syndrome in hyperparathyroidism]. PMID- 4017890 TI - [Crohn disease--an entity or just a syndrome?]. PMID- 4017892 TI - [Incidence of fatty liver in Germany. A pathoanatomo-epidemiologic study]. PMID- 4017893 TI - [Microcarcinoidosis of the stomach]. PMID- 4017895 TI - [Functional disorders of chamber demand (VVI) and sequential AV (DDD) pacemakers caused by muscle potentials]. AB - Muscle potentials as a cause of pacemaker malfunction are often unrecognized, because control examinations are usually performed without physical exercise. Two observations are cited to illustrate how malfunctioning of different modes of stimulation can be caused by interference from muscle potentials. In addition to the known suppression of impulse production, fixed-rate stimulation may occur. These observations indicate that pacemaker function should be tested also during physical activity. Any malfunction can almost always be stopped by re-programming amplifier sensitivity. PMID- 4017894 TI - [Importance of animal epithelia as house dust allergens]. AB - Among sera from 379 patients with atopy tested with the radio-allergo-sorbent test (RAST) for domestic dust and house-dust mite (Dermatophagoides pteronyssinus), 104 were positive only for house dust. Positive results for both house dust and house-dust mites were obtained in 130, while in 145 the RAST result was positive only for house-dust mites. 104 sera, negative for house-dust mites, were tested by RAST for specific IgE against epithelia from cats, dogs, guinea-pigs, horses and cattle, as well as cockroaches (Blatella germanica). A positive RAST result for at least one of these animal epithelia was obtained in 89.5% of sera, for cockroaches in 7.7%. Cat epithelia were of special importance with respect to both rate and degree of sensitization. Except for dog epithelia, sensitization (as demonstrated with RAST) against the other domestic animal epithelia was more frequent than the history had indicated. After immune adsorption of its homologous specific IgE with cat epithelia, but not after adsorption with epithelia of dog, guinea-pig, horse and cattle, inhibition of the house-dust RAST level in 60-80% was demonstrated in pool-sera. This finding proves that sensitization to cat epithelia, in addition to house-dust mites, can be the cause of a positive house-dust RAST reaction; cat epithelia are an important allergen of inhalation allergies caused by house dust. PMID- 4017896 TI - [Monitoring studies in patients with a cardiac pacemaker]. PMID- 4017897 TI - Chronic toxicity and oncogenicity bioassay of inhaled ethyl acrylate in Fischer 344 rats and B6C3F1 mice. AB - Male and female Fischer 344 rats and B6C3F1 mice were exposed to 0, 25 or 75 ppm (0, 0.10 or 0.31 mg/l) ethyl acrylate vapors, 6 hours per day, 5 days per week, for a total of 27 months. Additional rats and mice were exposed to 225 ppm (0.92 mg/l) for 6 months and then held for 21 additional months post-exposure. Histopathologic changes in olfactory portions of the nasal mucosa were present in animals in all of these three exposure groups. These microscopic exposure-related changes were concentration-dependent, primarily in terms of distribution of the lesions within the nasal cavity. Generally those areas of the nasal mucosa normally lined by olfactory epithelium were altered, while the regions lined by respiratory epithelium were relatively unaffected. There was no indication of an oncogenic response in any organ or tissue in either rats or mice. A follow-up study in which Fischer 344 rats and B6C3F1 mice were exposed to 5 ppm (0.02 mg/l) for 24-months revealed no treatment-related changes in the nasal mucosa. PMID- 4017899 TI - Influence of chronic lead ingestion on IgG subclass expression of the immune response to bovine serum albumin. AB - Rats were given free access to drinking water containing 2% lead acetate for 30 days prior to intraperitoneal inoculation with 100 mcg of bovine serum albumin (BSA) in Freund's complete adjuvant. Three weeks later, the animals were boosted with the antigen in Freund's incomplete adjuvant. After an additional three weeks, the animals were bled and the sera assayed for total IgG by radial immunodiffusion and for specific IgM, IgG and IgG subclasses by the enzyme-linked immunosorbent assay (ELISA). BSA-inoculated rats exhibited similar levels of total IgG regardless of exposure to lead, but showed significant increases in IgG compared to nonimmunized controls. However, levels of IgG specific for BSA were significantly lower in the lead exposed group. Analysis of the IgG subclasses specific for BSA revealed that BSA-inoculated rats which were not exposed to lead had greater titers of IgG2b and IgG2c as compared to the lead exposed group. Chronic lead ingestion appears to diminish the overall IgG response to BSA and may alter the normal IgG subclass expression. PMID- 4017898 TI - The acute toxicity and primary irritancy of N-benzyl-N,N-dimethylamine. AB - N-Benzyl-N,N-dimethylamine (BDMA), a polyester foam catalyst, was determined to have LD50 values of 0.65 (0.48-0.88) ml/kg perorally in the rat, and 1.66 (1.35 2.04) ml/kg by 24-hr occluded dermal contact in rabbits. The Lt50 for saturated vapor atmosphere exposure of rats was 35.4 min, and the 4-hr LC50 was 373 (311 447) ppm for rats and mice. Histological examination of the respiratory tract of animals exposed to BDMA concentrations of 277 ppm or higher revealed acute inflammatory changes in the nasal mucosa and pulmonary congestion. Unoccluded skin contact with 0.01 ml undiluted BDMA in rabbits produced moderate local erythema and edema. A 4-hr occluded contact resulted in local necrosis. Severe eye irritancy was produced by 0.005 ml undiluted BDMA and 0.5 ml 5% BDMA in propylene glycol; 1% BDMA was nonirritant to the eye. BDMA should be regarded as an acutely hazardous material by all routes of exposure. PMID- 4017900 TI - Radioiron utilization and gossypol acetic acid in male rats. AB - The 24-h incorporation of 59Fe into circulating red blood cells, bone marrow, urine, liver, spleen, and skeletal muscle was measured in splenectomized and sham splenectomized rats which had received a daily, oral dose of gossypol acetic acid (20 mg GAA/kg body wt) for 91 days. A significant decrease in total body weight gain was observed in all GAA treated animals. Splenectomized rats dosed with GAA exhibited a significant decrease in hemoglobin concentration, hematocrit and erythrocyte count. A significant increase in 59Fe incorporation by red blood cells and a decrease in hepatic incorporation of 59Fe indicate a preferential utilization of iron in erythropoiesis among GAA treated animals. PMID- 4017901 TI - [Epicutaneous tests]. PMID- 4017902 TI - [Dermatitis herpetiformis--from celiac disease to skin rash]. PMID- 4017903 TI - [General aspects of malignant melanoma]. PMID- 4017904 TI - [Phototherapy]. PMID- 4017905 TI - [Topical treatment of psoriasis]. PMID- 4017906 TI - [Vocational counseling and skin diseases]. PMID- 4017907 TI - [Paralytic poliomyelitis epidemic in Finland 1984-85]. PMID- 4017908 TI - [Peroneal nerve entrapment]. PMID- 4017909 TI - [Bannwarth's syndrome--a spirochetal cause of meningoradiculitis]. PMID- 4017910 TI - [Staphylococcus saprophyticus as a urinary tract pathogen]. PMID- 4017911 TI - [Lyme disease in Finland]. PMID- 4017912 TI - [Chromomycosis]. PMID- 4017913 TI - [Spasticity and its treatment]. PMID- 4017914 TI - An unidentified helminth egg in human stool. PMID- 4017915 TI - Results, indications and contra-indications of surgery in restrictive endomyocardial fibrosis: comparative study on 31 operated and 30 non-operated patients. PMID- 4017916 TI - Carbamazepine in manic depressive psychosis. PMID- 4017917 TI - Leucocyte counts during pregnancy and the puerperium and at birth in Nigerians. PMID- 4017918 TI - The prognostic significance of leukoerythroblastic anaemia in Nigerians. PMID- 4017919 TI - Rarity of iron deficiency in sickle-cell anaemia in northern Nigeria. PMID- 4017920 TI - Haematological indices of primary school children in Vwang Plateau State, Nigeria. PMID- 4017921 TI - Thyroid carcinoma in Enugu--Eastern Nigeria. PMID- 4017922 TI - Oral glucose tolerance test in children with sickle cell anaemia. PMID- 4017923 TI - The value of routine chest radiograph in chronic asthma in the tropics. PMID- 4017924 TI - Teratoma of the ovary in a three month old baby. PMID- 4017925 TI - Practical therapeutics: the use of carbamazepine in affective disorders. PMID- 4017926 TI - [Risk-benefit relation of liver biopsy in unclear jaundice]. AB - On the basis of an analysis of 125 liver biopsies in cases of unclear jaundice (mean bilirubin level 96 mumol/l, mean level of AP 1,78 mumol/l X s, of gamma GT 8,48 mumol/l X s, biopsy on an average on the seventh day of jaundice) the relation of risk and benefit of a liver biopsy is assessed. The benefit of the intervention being carried out with small expenditure of material and time and with minimal stress for the patients consists above all in the praeoperative exclusion of hepatitis and in the proof of cholestatic liver parenchyma diseases, which should not be operated on. In contrast to other authors no increased risk of the percutaneous liver biopsy during the first 10 (-14) days of jaundice (independent of the level of biochemical parameters of cholestasis) was stated (no biliary peritonitis, lethality rate 0%). The modern procedures of direct cholangiography are not seen as competing methods of examination but as such complementing each other with the liver biopsy. PMID- 4017928 TI - [Fine-structure roentgen analysis for the determination of gallstone components]. AB - Results of the determination of the chemical composition of human gallstones using X-ray diffraction method are reported. With simple handling it is possible beside identification of some other components to distinguish stones rich or poor in cholesterol already for smallest amounts of sample (greater than or equal to 10 mg, for instance endoscopically obtained material). This is significant with respect to the conservative medicamental therapy of lysis. PMID- 4017927 TI - Barium granuloma of gastroesophageal junction causing progressive dysphagia. AB - The authors observed for the first time a barium granuloma of the gastroesophageal junction that led to progressive dysphagia. The patient was fully cured by a radical excision of the granuloma and by esophagofundoplasty. The most probable way of development of the granuloma is thought to be by the author the retention of barium sulphate in a peptic subcardial ulcer during the X ray examination, which did not recognize it. PMID- 4017929 TI - [Effect of alcohol on the development of biochemical and morphologic findings of liver damage in the rabbit]. AB - Ethanol 48% was applied to the experimental model in 3 examined groups of rabbits in different periods of administration and differentiated daily doses on order to investigate the influence of ethanol upon the formation of morphological and biochemical indices of the liver lesion. Biochemical investigations were carried out on 3 and 7 day of the experiment and repeated at week by intervalls. All the animals were dissected and morphological examinations of the liver were carried out. Total analysis of the results obtained of the biochemical and morphological examinations of the liver in 3 analysed groups of animals proved that the biochemical index of postalcoholic lesion of the liver was a rise in guanase activity, and not in activity aminotransferases. In the investigations of fat balance, however the increase of triglycerides and cholesterol was observed. Morphological examinations showed post-alcoholic lesions of the liver, especially intensified in animals under longlasting alcohol influence, but in reducted doses. PMID- 4017930 TI - [Possible zymosan stimulation of the immune response of BALB/c mice to sheep erythrocytes and tumor target cells]. AB - Zymosan and its combinations with cyclophosphamide were tested for their effect on various immune responses. Zymosan alone had only minor effect on the cytotoxicity of lymphocytes to allogeneic and syngeneic tumour cells but significantly stimulated delayed-type hypersensitivity response, rosette formation and plaque forming cell response to sheep red blood cells in normal mice. Zymosan diminished immunosuppressive action of cyclophosphamide on the plaque and rosette formations and nonspecific allogeneic lysis of target cells by lymph node lymphocytes. Delayed-type hypersensitivity skin reaction and syngeneic T-killer cell activity increased significantly after the procedure of combination therapy. Lymphocyte stimulation action by the polysaccharide depended on the injection schedule used. Preliminary injection of zymosan was an optimal condition for enhancement of the cellular immune response. PMID- 4017931 TI - [Comparative characteristics of the adrenal and gonadal functions in human beings and hamadryas baboons with hemoblastosis]. AB - Adrenal and gonad steroid hormones were investigated in the peripheral blood plasma of human beings and hamadryas baboons (Papio hamadryas) with hemoblastosis. The similar hormonal dysfunction of adrenal glands and gonads was found in human beings and monkeys. The dehydroepiandrosterone level was found to decrease significantly, while the cortisol level increased markedly. Changes in the androgen level were sex-dependent. The testosterone and 5 alpha dihydrotestosterone levels were found to decrease markedly in men and male baboons while the testosterone level in women and females was found to increase significantly with 5 alpha-dihydrotestosterone unchanged. PMID- 4017932 TI - [Local blood flow into tumors during artificial hyperglycemia]. AB - The blood flow in the rat Guerin carcinoma was measured by the hydrogen clearance method. It was shown that the blood flow in the tumour tissue decreased almost 3.5 times to the 3 hours of the intravenous glucose infusion at a dose of 80 mg X kg-1 X min-1. In some tumours the microcirculation ceased completely. The results obtained help developing the new schemes of local hyperthermia and induced hyperglycemia in the complex antitumour therapy. PMID- 4017933 TI - [Antitumor activity of Ca-double-stranded RNA from sodium nucleinate]. AB - Ca-dsRNA introduced in the concentration of 5 micrograms per mouse 24 hours before the MG22a mouse hepatoma transplantation causes the 70% inhibition of the hepatoma growth. The sodium nucleinate used in the considerably higher concentration had a less effect. The sodium form of dsRNA also had a less antitumour effect comparing with its calcium form. The calcium form of dsRNA proves to be relatively stable and physiologically active form of dsRNA during its parenteral administration. PMID- 4017934 TI - [Changes in the chemotherapy sensitivity of leukemia L1210 cells during the development of diazan resistance]. AB - L 1210 leukemia strain resistant to diazan (L 1210/D1) was studied for its drug sensitivity in comparison with the parent strain. The resistant strain exhibited significantly higher sensitivity to nine drugs: dopan, sarcolysine, apirazidin, cyclophosphane, 6-mercaptopurine, thiophosphamide, rubomycin, vinblastine and vincristine. L 1210/D1 gained cross resistance to four drugs: 1-(2-chloroethyl)-3 (2, 6-dioxy-3-piperidyl)-1-nitrosourea, methotrexate, 5-fluorouracil and ftorafur. The resistant strain sensitivity remained unchanged (in comparison with the parent strain) to seven drugs: degranol, prospidin, nitrosomethylurea, chlorozotocin, deazauridine, bleomycin and L-asparaginase (crasnitine). PMID- 4017935 TI - [Ribamidyl (ribavirin) as a modulator of the biological action of arabinosylcytosine and methotrexate]. AB - Administration of ribamidyl (Rb) prior to Ara-C to intact mice or mice with implanted tumours enhanced Ara-C toxicity. The growth of tumours (plasmacytoma MOPC-21, adenocarcinoma of the small intestine (strain AKATON), mammary adenocarcinoma 755 (Ca 755) resistant to Ara-C or Rb was inhibited after coadministration of these drugs. The augmentation of toxic and antitumour effects of Ara-C by Rb is similar to the described effect of high doses of thymidine. This is in accordance with the enhancement of the intracellular pool of thymidine phosphates under the action of Rb. The toxicity of methotrexate in vivo was increased by coadministration with Rb. This effect may be connected with a decrease in purine precursors pool under the action of Rb. PMID- 4017936 TI - [Effect of phenobarbital and SKF 525-A on the toxic and therapeutic action of adriamycin in mice with Ehrlich ascites cancer]. AB - The toxic action of adriamycin (AD) in mice with the ascitic Ehrlich carcinoma was reduced by preliminary administration of phenobarbital (PB), an inductor of liver monooxygenases, and was increased after administration of SKF 525-A, an inhibitor of this enzymatic system. PB and SKF decrease the therapeutic action of AD. Incidentally, induction or inhibition of the liver enzymes was equivalent to the decrease in the AD dose in mice with the intact liver. It was also shown that the essence of PB and SKF influence on the AD therapeutic effect is its action on liver monooxygenases activity and not the interaction between PB or SKF and AD or the change of AD sensitivity of tumour cells. The possible role of cytochrome P 450 in manifestation of the AD toxic and therapeutic activity is discussed. The authors believe that for prevention of AD toxicity in patients with liver disorders the treatment following stimulation of the liver metabolic activity up to the normal liver level may be effective. PMID- 4017937 TI - [Measurement of basal plasma levels of 3 anterior pituitary hormones during acute or chronic treatment with tricyclic antidepressants]. AB - Prolactin, growth hormone and thyrotropin plasma levels have been evaluated in depressive in-patients, either during the first day of clomipramine or amitriptyline treatment, or after their chronic administration. Prolactin levels temporary rise during the first day of clomipramine or amitriptyline treatment in 6 patients out of 11, with a lag in relation to the drug plasma peak. A significant increase is observed after a 28 days treatment with clomipramine and a non significant decrease, after a 28 days treatment with amitriptyline. As for human growth hormone, a rise is found in 5 out of 8 clomipramine treated subjects but neither any variation with amitriptyline nor any significant variation with chronic administration of both drugs occur. Finally, thyrotropin plasma levels display no variation after acute or prolonged treatment with clomipramine or amitriptyline. These results are compared with those of literature, then discussed in the light of present theories on pituitary hormones secretion aminergic control and of tricyclic antidepressants effect on these hormones. PMID- 4017938 TI - [Changes in cerebral calcium, sodium and potassium after single or repeated administration of lithium in the rat]. AB - A single administration (IP) of lithium chloride in the rat induces a decrease in erythrocyte calcium, proportional to the lithium level (p less than 0.01) and a diminution in cerebral calcium (p less than 0.001) which is accompanied by decrease in cerebral sodium and potassium levels (p less than 0.001). Repeated administration (IP + VO) has the same cerebral effects. The authors report that the reversible decrease in calcium, sodium and potassium, resulting from an increase in cerebral lithium levels, can be demonstrated on sampling at 1.30 and 3 hours (IP), or at 12 hours (VO). These results are relevant to the treatment of manic illnesses using calcium antagonists. PMID- 4017939 TI - [Action of clovoxamine on the sleep of depressed patients. "Polygraphic recordings"]. AB - This study reports the action of clovoxamine, a non-tricyclic non IMAO antidepressant, on the sleep parameters of five patients suffering from primary depressive illness. Before treatment all subjects presented an EEG syndrome of primary depressive sleep disorder (decreased paradoxical sleep latency). Sleep recordings were made after 1 month and 3 months of monotherapy with clovoxamine. PS latency increased to normal values, sleep efficiency improved and wake time decreased, and, more remarkably, paradoxical sleep was not suppressed by clovoxamine. PMID- 4017940 TI - [Lithium levels in biological media and treatment surveillance]. AB - The authors present their collection procedures and the results concerning plasma, red blood cell or urinary lithium levels. They point out the interest of determination of red blood cell lithium for the prevention of toxical effects and the control of treatment in lithium intoxications. Clearance determination methodologies are also discussed. PMID- 4017942 TI - Symposium on emergency department radiology. PMID- 4017941 TI - [Methodology of post-mortem research. Apropos of setting-up a data bank for studying the biology of depression]. AB - Investigation of post mortem neurobiochemical changes is an important field in biological psychiatry which allows analyses of the analogies between peripherical markers and the central neurochemical processes they represent. Our study discusses the pathological neuroanatomy (collection and conservation of the anatomical specimens) and clinical criteria (selection of an evaluation and diagnostic scale, analysis of results of retrospective clinical interviews: "the psychological autopsy"). We also discuss the many methodological issues which arise in interpretations of these correlations. We wish to encourage others to apply a standardized methodology to these scientific studies of post mortem neurochemical parameters and retrospective clinical diagnosis. PMID- 4017943 TI - Bovine renal mitochondrial vitamin D3 hydroxylases: regulation of in vitro activities by inhibitors and antioxidants. AB - The regulation of bovine renal 1 alpha- and 24-hydroxylase activities was examined in primary bovine proximal tubule cell cultures. Maximal 1 alpha- and 24 hydroxylase activities in primary bovine proximal tubule cultures ranged from 1.5 1.8 and 2.0-2.7 pmol/min X 10(6) cells, respectively. The apparent Km was 795 nM for 1 alpha-hydroxylase activity and 1130 nM for 24-hydroxylase activity. 1 alpha and 24-hydroxylase activities decreased in primary culture after cell plating. Activities decreased both as a function of cell number and as a function of the culture dish. 1 alpha-Hydroxylase activity decayed with a t1/2 of 37 h, while 24 hydroxylase activity decayed with a t1/2 of 45 h. Decreasing cell densities, at which cells were plated, increased the t1/2 for the decay of both activities [t1/2 = 21 h at 5,000 cells/cm vs. t1/2 = 37 h at 25,000 cells/cm for 1 alpha hydroxylase (P greater than 0.001); t1/2 = 33 h at 5,000 cells/cm vs. t1/2 = 45 h at 25,000 cells/cm for 24-hydroxylase, (P greater than 0.0001)]. Direct addition of 0.25 mM metyrapone inhibited 1 alpha-hydroxylase activity by 33% and 24 hydroxylase activity by 51%. Long term incubation of cell cultures with 0.25 mM metyrapone resulted in a slowing in the loss of both hydroxylase activities, but did not stop the decay. 1 alpha-Hydroxylase activity in 4-day metyrapone-treated cultures was 35% higher than in 4-day untreated cultures. 24-Hydroxylase activity was increased 42% in treated cultures vs. that in untreated cell cultures. Both 1 alpha- and 24-hydroxylase activities were inhibited by direct addition of antioxidants. 1 alpha-Hydroxylase activity was directly inhibited 74% by the addition of 0.1 mM butylated hydroxyanisole (BHA), 69% by the addition of 0.1 mM butylated hydroxytoluene (BHT), and 56% by the addition of 0.05 mM benzyl sulfoxide (BS). 24-Hydroxylase activity was also directly inhibited 72% by 0.1 mM BHA, 55% by 0.1 mM BHT, and 73% 0.05 mM BS. There was no significant difference between the inhibition of either hydroxylase by each antioxidant. Antioxidant mixtures increased the inhibition of hydroxylase activities above that with single antioxidant. The addition of 0.1 mM BHA and 0.05 mM BS to cultures resulted in 100% inhibition of 24-hydroxylase activity and 95% inhibition of 1 alpha-hydroxylase activity. The results were very similar when 0.01 mM BS and 0.1 mM BHT were added to cultures, i.e. 100% and 91% inhibition of 24- and 1 alpha hydroxylase activities.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 4017944 TI - Metabolism of high density lipoproteins reconstituted with [3H]cholesteryl ester and [14C]cholesterol in the rat, with special reference to the ovary. AB - In order to study the metabolism of high density lipoprotein (HDL)-carried sterol in the rat, human HDL was reconstituted with [14C]cholesterol and [3H]cholesteryl ester. After iv injection into immature PMSG-human CG primed rats pretreated with 4-aminopyrazolopyrimidine and aminoglutethimide, there was time-dependent accumulation of 3H and 14C in various organs which reached a maximum by 15-90 min. On a milligram wet weight basis, uptake of 3H and 14C was greatest in the adrenals, next in ovaries, followed by the liver, with little uptake by kidneys and spleen. On an organ basis, accumulation was greatest by the liver. At 15-45 min post injection, 60% of the 3H in the ovary was in free sterol, indicating hydrolysis of the accumulated cholesteryl esters, whereas 95% of the 3H in serum remained in sterol esters associated with HDL. Coadministration of excess unlabeled HDL, but not human low density lipoprotein, reduced accumulation of radioactivity by the ovaries and adrenals by 60%, indicating a specific and saturable uptake process. Granulosa cells cultured in lipoprotein-deficient medium with reconstituted HDL formed 3H- and 14C-labeled 20 alpha-hydroxypregn-4 en-3-one. Over a 24-h period, utilization of both [14C]cholesterol and [3H]cholesteryl ester was linear, but rates of utilization of the two sterol moieties were not parallel. There was preferential uptake and utilization of free sterol. A dose-response study demonstrated a Michaelis-Menten constant (Km) of 40 60 micrograms sterol/ml for both free and esterified cholesterol. Lysosomotropic agents (chloroquine and NH4Cl) had no effect on utilization of either free or esterified cholesterol for steroidogenesis but reduced degradation of 125I labeled low density lipoprotein apoprotein. These findings lend further support to the concept of a distinct HDL pathway in steroidogenic cells of the rat, which involves 1) preferential uptake and utilization of free cholesterol from HDL and 2) does not require lysosomal activity. PMID- 4017945 TI - Characterization of the subunit nature of nuclear estrogen receptors by chemical cross-linking and dense amino acid labeling. AB - We have used chemical cross-linking and dense amino acid labeling of estrogen receptors to characterize the subunit nature and rate of turnover of nuclear 5S estrogen-receptor complexes. When MCF-7 human breast cancer cells are incubated with [3H]estradiol or [3H]antiestrogen [alpha-[4-pyrrolidinoethoxy]phenyl-4 hydroxy-alpha'-nitrostilbe ne (CI628M) or (Z)-1-[4-(2-[N aziridinyl]ethoxy)phenyl] 1,2-diphenyl-1-butene (tamoxifen aziridine)] and nuclear estrogen-receptor complexes are extracted with 0.6 M KCl and then chemically cross-linked with the cross-linker 2-iminothiolane, the cross-linked receptor complexes sediment as a 5.4S species on 3 M urea-containing sucrose gradients, while the noncross-linked species are 4S. Sodium dodecyl sulfate polyacrylamide gel analyses of these cross-linked nuclear receptor complexes labeled with the covalently attaching ligand [3H]tamoxifen aziridine reveal a species of about 130,000 mol wt, while the noncross-linked or the cross-linked but mercaptan-cleaved receptor is 65,000 mol wt. Both receptor species are also detectable by interaction with an immunoadsorbent column containing antireceptor monoclonal antibody. For analyses of receptor turnover rates, cells exposed for different time periods to medium containing dense (15N, 13C, and 2H) amino acids were labeled with [3H]antiestrogen [1-[4-(2-dimethylaminoethoxy)phenyl]1-[4 hydroxyphenyl] 2-phenylbut-1-(2)ene (trans-hydroxytamoxifen) or CI628M] or [3H]estradiol, and salt-extracted nuclear estrogen receptors were analyzed on sucrose gradients. The normal density 5S form shifted to a broader, more dense peak at 2 and 4 h and finally, by 8-10 h, to a more dense, sharply sedimenting species. The time course of this shift is the same as that seen for the 4S urea dissociated nuclear receptor form (t1/2 approximately 4h), suggesting that the 5.4S nuclear receptor is composed of two species which turn over at the same rate. We conclude from these cross-linking and density shift experiments that the nuclear 5S receptor complex consists of two similarly sized units, which turn over with similar half-lives. These data provide strong evidence that the 5S nuclear receptor complex is a homodimer of two 4S, 65,000 mol wt monomers. PMID- 4017946 TI - Noradrenergic and endogenous opioid pathways in the regulation of luteinizing hormone secretion in the male rat. AB - Endogenous opioid pathways (EOPs) appear to play a role in the tonic regulation of pulsatile LH secretion. The mechanism by which EOPs influence LH release is not known. However, the observation that acute chemical disruption of the noradrenergic (NE) system by alpha-receptor-blocking agents or NE synthesis inhibitors blocks the LH increase occurring in response to naloxone (NAL) suggests that the ability of EOPs to influence LH secretion may depend upon a functional NE system. We hypothesized that if EOPs required an interacting NE system to influence LH secretion, then rats that have ascending NE tract lesions would not respond to NAL with an increase in LH. To test this hypothesis, we challenged NE-lesioned and sham-lesioned rats with NAL. Young adult male rats received either a NE lesion or a sham lesion and 6 weeks later were implanted with jugular catheters. On the following day, four baseline blood samples (400 microliters at 10-min intervals) were taken from NE-lesioned and sham-lesioned rats. All rats were then challenged with 2 mg/kg NAL, iv, and four subsequent blood samples were taken. NAL significantly increased LH levels (P less than 0.01) in both the NE-lesioned (n = 7) and sham-lesioned (n = 8) rats. Mean LH responses above baseline for these groups were 0.52 +/- 0.12 ng RP-2/ml and 0.38 +/- 0.07 ng/ml, respectively. Failure of the NE lesions to block the LH response to NAL was not due to the presence of active residual NE fibers, because pretreatment with the alpha-receptor blocker phenoxybenzamine (20 mg/kg, iv) failed to block the NAL response in the NE-lesioned animals (n = 8), whereas it did so in the sham-lesioned animals (n = 7). The mean LH response from baseline after phenoxybenzamine pretreatment was -0.01 +/- 0.01 ng/ml for the sham lesioned group and 0.53 +/- 0.24 ng/ml for the NE-lesioned group. These results indicate that EOPs do not require noradrenergic mediation to influence LH secretion in the adult male rat. PMID- 4017947 TI - An evaluation of the role of antiestrogen-binding sites in mediating the growth modulatory effects of antiestrogens: studies using t-butylphenoxyethyl diethylamine, a compound lacking affinity for the estrogen receptor. AB - Tert-butylphenoxyethyl diethylamine (BPEA), a compound synthesized by us, was designed to incorporate features important in binding to antiestrogen-binding sites (AEBS) while lacking features important in binding to the estrogen receptor (ER). With this compound, we have addressed the question of the role of AEBS in mediating the growth modulatory effects of antiestrogens. BPEA has an affinity for AEBS 6% that of tamoxifen and an affinity for ER less than 0.0003% that of estradiol. BPEA (10(-11)-10(-6) M) had no effect on the growth of MCF-7 breast cancer cells and no effect on inhibition of the growth of MCF-7 cells by different concentrations of the antiestrogen tamoxifen. In addition, BPEA (even at doses of 1 mg/day X 50 g rat) exhibited no uterotropic or antiuterotropic activity in immature rats and had no influence on the agonistic or antagonistic activity of varying concentrations of tamoxifen on uterine weight. Hence, we conclude that occupancy of AEBS, at least by BPEA, does not modulate growth of the uterus or breast cancer cells and does not influence the potency of tamoxifen as an antiestrogen. These findings raise serious doubts about the role of the AEBS in mediating directly the growth modulatory effects of antiestrogens. PMID- 4017948 TI - Species differences in prostatic steroid 5 alpha-reductases of rat, dog, and human. AB - The conversion of testosterone to 5 alpha-dihydrotestosterone by prostate particulates from rats, dogs, and humans was investigated, and significant species differences were found with their pH profiles, affinities for 4 azasteroidal inhibitors, and sensitivities to mercuric sulfhydryl reagents. The pH optima for the rat (pH 7), the dog (pH 6), and the human (pH 5) enzyme are significantly different. Mersalyl acid and p-hydroxymercuribenzoate inactivate only the rat 5 alpha-reductase, but not the human or dog enzyme. The rank orders of potencies of 24 3-oxo-4-azasteroids to inhibit 5 alpha-reductases of the rat, dog, and human prostate are different. The variation of the 17 beta-functional groups of the inhibitors demonstrates clearly the species differences. Those inhibitors with a 17 beta-diethylcarbamoyl, 17 beta-diisopropylcarbamoyl, 17 beta t-butylcarbamoyl, or 17 beta-secbutylcarbonyl functional group are approximately equipotent as inhibitors of the rat and human enzymes, whereas they are only 0.1 15% as potent as inhibitors of the dog enzyme. On the other hand, those inhibitors with a 17 beta-spiroether functional group are most potent as inhibitors of the rat enzyme, are 15-50% as potent as inhibitors of the dog enzyme, and are 0.2-0.4% as potent as inhibitors of the human enzyme. Those inhibitors with a 17 beta-n-octylcarbamoyl, 17 beta-(1-carboxyethyl), or 17 beta (1-carboxy-3-butyl) functional group are 2-3 orders of magnitude less potent as inhibitors of the dog and human enzymes than as inhibitors of the rat enzyme. These results suggest that prostatic 5 alpha-reductases of rats, dogs, and humans are significantly different. In spite of the significant species differences in inhibitor affinities, where determined, inhibition of the rat, dog and human enzymes by these compounds is competitive with testosterone. These 3-oxo-4 azasteroids have a similar rank order of potency as inhibitors of 5 alpha reductase in human normal, benign hyperplastic, and cancerous prostates, indicating that the inhibitor-binding sites of 5 alpha-reductase in the prostate in different pathological states are similar. The affinities of the 3-oxo-4 azasteroids for rat prostatic cytosol receptor were determined. Five of these 5 alpha-reductase inhibitors have no significant affinity for the androgen receptor, whereas others do have an affinity for the receptor. PMID- 4017949 TI - Effects of high doses of iodide on thyroid secretion: evidence for the presence of iodinated membrane tubulin. AB - The transient inhibitory effect on thyroid secretion produced by high doses of iodide was investigated with respect to changes in the level of in vivo iodination of membrane tubulin. Iodinated tubulin, characterized by gel electrophoresis, immunoprecipitation, and peptide mapping, was shown to be associated with a thyroid membrane fraction, and totally absent from cytoplasmic proteins. The administration of an acute dose of 5 mg KI, although it inhibited thyroid secretion (as shown by an increase in TSH), did not have a significant effect on the level of iodination of membrane tubulin. Thus, the observed inhibition of thyroid secretion is probably unrelated to the level of iodination of tubulin. Although its function is not known at present, iodinated tubulin is probably involved in membrane-related phenomena. PMID- 4017950 TI - Thyroid hormones increase renal brush border membrane transport of phosphate in X linked hypophosphatemic (Hyp) mice. AB - Hyp mice, the murine homolog of human X-linked hypophosphatemia (XLH), are characterized in part by elevated renal loss of phosphate (Pi) and hypophosphatemia. The lesion responsible for this syndrome is believed to be defective Na+ gradient-dependent phosphate transport across renal brush border membranes (BBM). It has been demonstrated that thyroid hormones can stimulate Pi uptake by rat BBM vesicles (BBMV). The purpose of this current study was to determine whether thyroid hormones could increase renal BBMV transport of Pi and improve the renal conservation of Pi in Hyp mice. Hyp mice were treated with either vehicle (controls) or T4 (0.2 mg/100 g BW, ip, once daily) for 6 days. At the end of the treatment period, the uptake of 32Pi (at 30 sec), in the presence of a Na+ gradient (Na+o greater than Na+i) by BBMV prepared from renal cortex of T4-treated Hyp mice, was significantly increased (+25%) compared to that in vehicle-treated Hyp controls. The uptake of L-[3H]proline (at 10 sec) by the same BBMV preparation was unchanged. T4-treated Hyp mice displayed a significant decrease in urinary Pi excretion (-31%), and a restoration of plasma Pi levels (+52%) to the normal range. Plasma calcium, creatinine, and magnesium as well as urinary excretion of cAMP did not change with T4 treatment. Another group of Hyp mice was given T3 (0.2 mg/100 g BW, ip) at three 12-h intervals. After 36 h, the rate of 32Pi uptake by renal BBM was significantly increased (+40%). Plasma Pi also increased (+26%). Our findings indicate that parenteral administration of thyroid hormones specifically increased (compared to transport of L-proline) the capacity of Na+ gradient-dependent renal BBM Pi uptake in Hyp mice, decreased renal Pi excretion, and increased plasma Pi. These results suggest that treatment with T4 or T3 can enhance the defective proximal tubular reabsorption of Pi and improve renal Pi retention in murine X-linked hypophosphatemia. PMID- 4017951 TI - Elevated catecholamines in porcine follicular fluid before ovulation. AB - The purpose of this study was to correlate changes in catecholamine concentrations in porcine follicular fluid and cyclic events in the ovary. Follicular fluid was aspirated from follicles of ovaries obtained from pigs throughout the 21-day estrous cycle and analyzed for norepinephrine (NE), epinephrine (EPI), and estradiol (E2). Serum was obtained from cycling pigs on days 6-10 and 16-20 of the cycle and assayed for NE, EPI, E2, and progesterone. The concentrations of NE in the follicular fluid were relatively constant during days 1-15 of the luteal phase (1.7 +/- 0.2 ng/ml), but were elevated significantly to 2.9 +/- 0.4 ng/ml during the follicular phase (days 16-20). EPI had a similar profile, but a 6- to 10-fold lower concentration. The follicular fluid E2 concentration increased from 15.6 to 76.5 ng/ml during the luteal phase to 630 ng/ml during the follicular phase. Serum NE and EPI concentrations were similar during midluteal and follicular phases, whereas progesterone and E2 were significantly elevated during the luteal and follicular phases, respectively. These results indicate that catecholamines in follicular fluid are elevated significantly during the follicular phase of the estrous cycle and may have a physiological role in preovulatory events as well as during the luteinization process. PMID- 4017952 TI - In vitro simulation of prepubertal changes in pulsatile luteinizing hormone release enhances progesterone and 17 beta-estradiol secretion from immature rat ovaries. AB - We have previously demonstrated changes in the episodic pattern of LH secretion in female rats as they approach first ovulation. In the present study, ovaries were taken from peripubertal rats and perifused in vitro with a medium containing FSH and LH. The concentration of FSH in the medium was kept constantly low, whereas the concentration of LH was modulated, simulating as closely as possible the various episodic secretory profiles previously observed in vivo. Medium from the perifusion chambers was collected every 10 min for 5 h and assayed for progesterone (P) and 17 beta-estradiol (E2). Exposure of the ovaries to low amplitude LH pulses (20 ng/ml; comparable to those found in the plasma of peripubertal rats during the morning) did not elicit a significant steroidogenic response. On the other hand, exposure to large amplitude LH pulses (80 ng/ml; as seen during the afternoon) led to a marked increase in the output of both P and E2. Similarly, increased steroid secretion occurred when ovaries were exposed to a 2-h minisurge of LH (160 ng/ml) or to a minisurge preceded by three large amplitude pulses (as seen in some animals during the afternoons of the peripubertal period). Continuous exposure to LH at concentrations similar to either the large amplitude pulses or the LH minisurge increased P and E2 release. However, the increase was not significantly larger than that produced by the discontinuous LH perifusion patterns, even though the total amount of LH reaching the ovaries during the 5-h perifusion period was considerably greater. The results show that episodic LH secretion is functionally much more efficient at eliciting release of P and E2 from immature ovaries than is continuous LH secretion. Furthermore, they strongly suggest that changes in the LH secretory pulse patterns, as seen in vivo close to the time of puberty, are fundamental for the activation of ovarian steroidogenesis that leads to the first preovulatory surge of gonadotropins. PMID- 4017953 TI - Vulnerability to stress-induced tumor growth increases with age in rats: role of glucocorticoids. AB - Aged males rats show a delay in terminating their adrenocortical stress response and, thus, hypersecrete corticosterone during the poststress period. Because of the numerous catabolic effects of corticosterone, we hypothesized that chronic stress should induce greater pathophysiological changes in aged than in young subjects. We report that stress-induced tumor growth, associated with inoculation with fetal rats cells transformed by tumor virus, is accelerated in aged rats. Furthermore, simulation of the aged pattern of corticosterone hypersecretion in young animals using steroid administration similarly accelerates stress-induced tumor growth. PMID- 4017954 TI - The functional state of the dopamine receptor in the anterior pituitary is in the high affinity form. AB - In order to determine whether the high affinity state or the low affinity state of the dopamine receptor mediated the inhibition of release of PRL by dopamine agonists, a large number of dopaminergic agonists (n = 31) and antagonists (n = 24) were tested for their potencies to inhibit the binding of [3H] spiperone to porcine anterior pituitary tissue, and for their potencies to affect the release of PRL from rat anterior pituitary cells in culture. All agonists (except bromocriptine, ergocryptine, and dihydroergocryptine) inhibited [3H]spiperone binding in two phases: one phase occurred at nanomolar or subnanomolar concentrations (representing the high affinity state of the dopamine receptor) and the other phase occurred at much higher concentrations of agonist (the low affinity state of the dopamine receptor). The dissociation constants (K) for each drug at each state were derived by computer, with the program LIGAND. It was observed that the agonist K values for the high affinity state were virtually identical with those agonist concentrations inhibiting PRL release; the K values for the low affinity state were about 2 orders higher. These data suggest that the high affinity state of the D2 dopamine receptor is the functional state which mediates the inhibition of PRL release. PMID- 4017955 TI - Effects of chronic prolactin administration on renal hemodynamics in the rat. AB - Experiments were performed to measure the systemic and renal hemodynamic effects of chronic PRL administration to female rats (in which pseudopregnancy was induced) and male rats. Studies were performed in rats of the Munich-Wistar and Sprague-Dawley strains. In micropuncture studies under anesthesia, no differences were seen in plasma volumes or whole kidney or glomerular hemodynamics in PRL injected rats compared to those sham-injected controls regardless of sex. In separate studies, observations were made in conscious, chronically catheterized female rats of the Sprague-Dawley strain. Neither the glomerular filtration rate nor the renal plasma flow rate was different on day 9 of PRL-induced pseudopregnancy compared to values in the control state in the same animals. Thus, PRL-induced pseudopregnancy does not cause increases in glomerular filtration rate, renal plasma flow rate, or single nephron GFR or its determinants, whereas in previous studies on pseudopregnancy resulting from a sterile mating, increases in glomerular and renal hemodynamics occurred which were indistinguishable from those seen during the first half of pregnancy in the rat. These data suggest that PRL is not involved directly in either the plasma volume expansion or increase in renal hemodynamics that occurs after mating in the rat. PMID- 4017956 TI - Bipotential actions of estrogen on progesterone biosynthesis by ovarian cells. II. Relation of estradiol's stimulatory actions to cholesterol and progestin metabolism in cultured swine granulosa cells. AB - Although both inhibitory and stimulatory actions of estradiol on swine granulosa cells have been described, the bases for these inconsistent effects are not clear. We have tested properties of ovarian follicles and in vitro culture conditions that result in consistently stimulatory effects of estradiol on progesterone biosynthesis. Stimulatory actions of estradiol (in contrast to inhibitory effects) were critically dependent upon the density of granulosa cells in culture and the size and maturational status of the parent Graafian follicles. Granulosa cells isolated from small, rather than medium or large sized, swine follicles exhibited the greatest peak response to estradiol, although half maximally stimulatory concentrations (ED50) of estradiol were similar (mean, 81 ng/ml). Granulosa cells from atretic follicles also secreted increased quantities of progesterone in response to estradiol, but the ED50 for estrogen stimulation was significantly higher (ED50 = 322 ng/ml estradiol) than that of comparable healthy follicles (ED50 = 109 ng/ml). This estrogen-responsive system was used to test the mechanisms subserving estrogen's trophic actions on granulosa cells. Estradiol significantly enhanced the activity of 3 beta-hydroxysteroid dehydrogenase with consequently increased production of progesterone and 20 alpha hydroxypregn-4-en-3-one. Estrogen also augmented functional cholesterol side chain cleavage activity in a dose- and time-dependent fashion with a resultant increase in pregnenolone biosynthesis. Moreover, parallel observations documented concordant dose responses for the synthesis of all three major progestins by pig granulosa cells. The trophic actions of estrogen on the steroidogenic pathway were associated with enhanced hydrolysis of endogenous cholesteryl ester stores but were not significantly antagonized by inhibition of de novo cholesterol biosynthesis. We conclude that suitable follicle selection and appropriate in vitro culture conditions provide a consistently estrogen-responsive granulosa cell system, in which estradiol modulates certain key aspects of progestin and cholesterol metabolism. These trophic actions of estrogen are likely to prepare granulosa cells for the increased rates of progesterone biosynthesis ultimately required by fully differentiated luteal cells. PMID- 4017957 TI - Triiodothyronine (T3)-induced thermogenesis: altered T3-efficiency in tissues from fed, starved, and refed hypothyroid rats. AB - A microcalorimetric study of perifused tissue samples obtained from hypothyroid thyroidectomized rats killed 15 h after a single injection of T3 was conducted in order to observe at the tissue level, and in a constant environment, the T3 dependent thermogenesis induced in fed, starved, and refed states. When 9 micrograms T3/100 g BW had been administered to fed animals, tissue heat production rate (E) increased in liver, soleus muscle, and myocardium. In kidney cortex an increase in E was observed only after 90 micrograms T3. A dose-response study was performed with liver samples, in which both oxygen consumption and heat production rates were measured. Liver and soleus muscle were then further investigated. T3-dependent thermogenesis could not be demonstrated in tissues obtained from rats which had been starved for 3 days before receiving 9 micrograms T3/100 g BW. After a small carbohydrate intake corresponding to about 60 kJ/rat (refed state; 1 kJ congruent to 0.4 kcal) given over a 3-h period preceding the injection of T3, T3-dependent thermogenesis was again present. It is concluded that differences in T3 dependent thermogenesis similar to those previously observed in animals under different nutritional states continue to exist in vitro, when tissues are no longer exposed to differing levels of humoral factors. PMID- 4017958 TI - Hormonal changes in burned hamsters. AB - Burned male Syrian hamsters (burn size 23% of body surface) exhibited reduced total (T4) and free (FT4) serum concentrations, a defect in T4 binding to serum proteins manifested by the T4 dialyzable fraction but not the in vitro T3 charcoal uptake, and reduced serum testosterone concentration. These changes are similar to those noted previously in burned humans. Unlike such patients, burned hamsters did not exhibit reduced serum T3 nor elevated rT3 concentrations in a reproducible manner. Pinealectomy performed before burning in hamsters did not prevent the burn-induced depression in serum T4 and testosterone. PMID- 4017959 TI - Changes in very low density lipoprotein particle size and production in response to sucrose feeding and hyperinsulinemia. AB - The effects of chronic (2 weeks) hyperinsulinemia on the production of very low density lipoprotein (VLDL) triglyceride and on VLDL particle size were examined. Hyperinsulinemia was induced by a constant sc infusion of 6 U porcine insulin/day from an osmotic minipump. To avoid profound hypoglycemia, these rats received chow plus 10% sucrose in their drinking water. Therefore, two control groups were examined; one receiving chow plus the same amount of sucrose (high carbohydrate control) and the other receiving chow only (chow control). The constant infusion model was compared to a previously reported model of hyperinsulinemia. In that model, NPH insulin was injected for 2 weeks twice daily in incrementally increasing doses (final dose, 6 U/day) into rats that were also fed chow and given 10% sucrose drinking water. Results with the injection model were similar to those previously reported: an increase in triglyceride production in face of a decrease in FFA, a minimal decrease in serum triglyceride, and some decrease in serum glucose. The infusion model produced the same increase in triglyceride production and decrease in fatty acid concentration. However, it differed in producing an increase in serum triglyceride and no change in serum glucose. The former suggested that in the infusion model triglyceride removal was not stimulated as much as in the injection model. Since there was no hypoglycemia in the infusion model, it was unlikely that VLDL changes were caused by an increase in counter regulatory hormones. VLDL particle size was increased in the high carbohydrate controls. This indicated that changes in sucrose supplementation led to the production of more triglyceride-filled VLDL particles. Hyperinsulinemia was not accompanied by any further increase in particle size. Thus, the hyperinsulinemia-induced increase in VLDL-triglyceride production was accompanied by an equivalent increase in VLDL particle production. PMID- 4017960 TI - 25-Hydroxycholesterol-supported and 8-bromo-adenosine 3',5'-monophosphate stimulated testosterone production by primary cultures of two populations of rat Leydig cells. AB - Previous studies from this laboratory have demonstrated the presence of two populations of rat Leydig cells (I and II), which differ in their capacity for hCG- or cAMP-stimulated testosterone production. In the present study, we examined the metabolism of 25-hydroxycholesterol in primary cultures of both populations of Leydig cells. 25-Hydroxycholesterol bypasses the cAMP-dependent transport mechanism to the mitochondrial cytochrome P-450 side-chain cleavage enzyme (P-450scc) required by cholesterol and thus provides an index of the relative activity of P-450scc. Incubation of Leydig cells with increasing concentrations of 25-hydroxycholesterol resulted in a concentration-dependent increase in the amount of testosterone produced, with maximal amounts in both populations being reached at 25-hydroxycholesterol concentrations of 5 microM or greater. Population II produced more than twice as much testosterone as population I Leydig cells, whether incubated with 25-hydroxycholesterol or with 8 bromo-cAMP. Each population of Leydig cells produced 2.5-fold greater amounts of testosterone when incubated with 25-hydroxycholesterol than when incubated with 8 bromo-cAMP. In both populations of Leydig cells, cAMP-stimulated testosterone production was not different in cells cultured for 24 h from that in freshly isolated Leydig cells. These data suggest that cholesterol transport to P-450scc limits maximal testosterone production, and that the difference in hCG- or cAMP stimulated testosterone production between the two populations of Leydig cells is primarily due to differences in P-450scc activity between the two populations and is not a result of population I consisting mostly of damaged Leydig cells. PMID- 4017961 TI - Vasopressin release in male and female rats: effects of gonadectomy and treatment with gonadal steroid hormones. AB - We have found, in normal Wistar rats 10-11 weeks old, that the plasma vasopressin concentration (PADH) and the 24-h urinary excretion of vasopressin (UADHV) were higher in males than in females (P less than 0.01). In rats that were gonadectomized when they were 3 weeks old and studied when they were 10-11 weeks old, PADH and UADHV were reduced in males (P less than 0.01) and increased in females (P less than 0.01 for UADHV; PADH not significant) compared to those in intact males and females, respectively. Treatment of castrated male rats with testosterone tended to increase PADH, but estradiol, progesterone, or a combination of estradiol and progesterone were without effect; UADHV was increased by testosterone (P less than 0.01) and lowered by estradiol plus progesterone (P less than 0.01). In ovariectomized rats, PADH was unaffected by either testosterone or estradiol, but was decreased by progesterone alone (P less than 0.05) or in combination with estradiol (P less than 0.05). In these ovariectomized rats, UADHV was unaffected by testosterone and was decreased by estradiol and progesterone individually or in combination (P less than 0.01). These findings suggest that the gonadal steroid hormones can act either centrally to affect ADH release or peripherally to affect ADH metabolism. Compared to intact male rats, the lower PADH in intact female rats was accompanied by lower urine osmolality and greater urine volume, but further study will be required to appreciate fully the physiological significance of the differing PADH in males and females. PMID- 4017962 TI - Concentrations of thyroxine and 3,5,3'-triiodothyronine at 34 different sites in euthyroid rats as determined by an isotopic equilibrium technique. AB - The present study was designed to assess the quantities of T4 and T3, and the source (i.e. plasma-derived vs. locally produced) of the latter iodothyronine, in various rat tissues. For this purpose, normal intact rats were brought to isotopic equilibrium by means of a continuous iv infusion of [125I]T4 and [131I]T3 for a prolonged period. At the end of the infusion period, the animals were bled and perfused. Either whole small organs or weighed portions of tissues were homogenized in saline. The iodothyronines were extracted with ethanol ammonia and separated by TLC. The [125I]T3/[131I]T3 ratios for the tissue homogenates and plasma were determined, and the relative contribution of the T3 derived from local T4 to T3 conversion [abbreviated: Lc T3 (T4)] to the total T3 in a given tissue was calculated. The endogenous T4 and T3 levels in the various organs were computed from the known specific activities of the labeled iodothyronines. The concentration of T4 in plasma greatly exceeded that found for tissue. Among the tissues examined, the T4 concentration was highest in the liver and lowest in cerebral cortex and cerebellum. T3 (per gram) was most abundant in the kidney and anterior pituitary gland and least abundant in the testis, epididymis, and erythrocytes. In contrast to the other tissues investigated, the concentration of T3 in several regions of the brain and anterior pituitary gland either equalled or exceeded that of T4. Plasma exhibited by far the lowest T3/T4 ratio. For most of the organs investigated the contribution of Lc T3(T4) appeared to be low. On the other hand, in 15 tissues, including the central nervous system, the local production of T3 accounted for one fifth or more of the total T3 content. Although there were no regional differences between the total T3 levels in the brain, the relative contribution of Lc T3(T4) was 65% in the cerebral cortex and only 22% in the spinal cord. The variation in the source of T3 in the various parts of the central nervous system may be related to regional differences in T4 and T3 metabolism. The fact that the present study demonstrates that the relationship between circulating T3 and intracellular T3 varies from one organ to the next may be important for accurate interpretation of plasma T4 and T3 levels and for designing optimal thyroid hormone replacement therapy for patients with hypothyroidism. PMID- 4017963 TI - The clearance and metabolism of estradiol and estradiol-17-esters in the rat. AB - The C-17 fatty acid esters of estradiol are naturally occurring estrogens which have been shown to circulate in blood. They are long-acting estrogens, analogous to the synthetic alkyl and aryl esters of estrogens which have been used pharmacologically for decades. To determine the mechanisms involved in the prolonged stimulation evoked by these nonpolar estrogens, several C-17 alkyl esters were synthesized and labeled with 3H at C-17 alpha, and their metabolism and clearance were studied and compared to those of estradiol in rats. The conversion of the C-17-3H to 3H2O was used as a marker of metabolism. While the clearance of the long chain esters from blood is somewhat slower than that of estradiol (t 1/2 = approximately 16 vs. 2 min, respectively), the rates of metabolism are dramatically different. For example, the t 1/2 of metabolism for two representative esters, estradiol-17-stearate and arachidonate, are 580 and 365 min, respectively, while the t 1/2 of metabolism for estradiol is about as fast as its clearance from blood (approximately 2 min). When the effect of chain length was studied, it was found that for the smaller esters, there was an inverse relationship between the size of the acyl group and the clearance from blood, i.e. the longer carboxylic acids were cleared more slowly. However, when the acyl group was lengthened from C12 to C14, the rate of clearance increased and was even faster with C18. Nevertheless, with all of the esters tested, the rate of metabolism steadily decreased as the chain length increased. These results are interpreted as indicating that the control point or rate-limiting step in the metabolism of the estradiol esters is the esterase that hydrolyzes the ester to estradiol. Thus, the prolonged estrogenic action of the C-17-alkyl esters is due to the slow release of estradiol from this hydrophobic reservoir. PMID- 4017964 TI - Maternal and fetal production rates of progesterone in rhesus macaques: placental transfer and conversion to cortisol. AB - Maternal and fetal progesterone (P4) metabolism and placental transfer were examined in vivo. Via a femoral vein, 3.2 microCi[14C]P4 were infused at a constant rate for 2 h into five rhesus macaques on days 131-137 of gestation. Simultaneously, 12 microCi[3H]P4 were infused into the fetuses via a placental bridging vein. Measurement of steady state concentrations of [14C]- and [3H]P4 in the maternal and fetal circulations permitted calculation of the MCRs, production rates (PRs), and transfer rates (Vs) of P4. The maternal MCR (533 liters/day) was higher than the fetal MCR (93 liters/day), whereas the maternal PR did not differ significantly from the fetal PR (2.3 and 1.0 mg/day, respectively). Placental transfer of P4 from the fetal to maternal circulation (VFM) was greater than that from the maternal to fetal circulation (VMF). Values were 0.23 and 0.07 mg/day, respectively. The utilization of circulating P4 as a substrate for fetal cortisol (F) production was examined in three additional monkeys for whom the amount of isotopically labeled P4 infusate was increased 5-fold. By determining the ratio of specific activities of [3H]F and [3H]P4 in the fetal circulation, we found the maximum contribution of circulating fetal P4 as a precursor of fetal F to be less than 1%. Our results indicate that: 1) higher fetal than maternal plasma P4 concentrations (11.3 and 4.3 ng/ml, respectively) are most likely the result of 5 fold lower fetal MCR, since the PRs are similar in the fetal and maternal compartments, and the VFM is greater than the VMF; and 2) fetal F production using circulating P4 as a substrate is minimal. PMID- 4017965 TI - Conformational requirements for activity of salmon calcitonin. AB - A series of deletion-substitution analogs of salmon calcitonin (SCT) have been prepared containing combinations of a glycine substitution in position 8 and deletions of serine-2 and tyrosine-22. Biological activity of the analogs with respect to native SCT were determined in the rat hypocalcemic assay and by studying stimulation of cAMP formation and competition for binding of 125I labeled SCT in T47 D human breast cancer cells. It was found that each of the analogs retained full potency, irrespective of the means of assessment. It is suggested that conservation of the alpha-helical region of SCT, along with the overall tertiary structure, are more important for peptide potency than chain length per se. PMID- 4017966 TI - Modulating influence of D,L-propranolol on triiodothyronine-induced skeletal muscle protein degradation. AB - There is evidence suggesting that thyrotoxicosis increases beta-adrenoreceptor density on some target tissues. We have studied the in vivo effect of D,L propranolol (a nonselective beta-adrenoreceptor blocking agent) on T3-induced enhancement of in situ proteolysis in fast twitch muscle fibers of the rat. Chronic treatment with T3 as opposed to saline resulted in a 76% enhancement of the rate of in situ muscle proteolysis [0.79 +/- 0.04 (n = 8) compared with 0.45 +/- 0.01 (n = 8) nmol tyrosine/mg muscle . 2 h]. Treatment of rats with both T3 and 2 mg propranolol resulted in a 62% reduction in the T3-induced increment in situ muscle proteolysis [0.58 +/- 0.02 (n = 8) vs. 0.79 +/- 0.04]. This significant inhibition by propranolol of T3-induced enhanced proteolytic rates in vitro suggests that this may comprise one component of the observed beneficial clinical effects of beta-blockade in thyrotoxic myopathy. PMID- 4017967 TI - Adrenocortical cell function in the hypophysectomized domestic fowl: effects of growth hormone and 3,5,3'-triiodothyronine replacement. AB - The control of adrenocortical function in the domestic fowl (Gallus domesticus) was investigated using adrenocortical cells isolated from hypophysectomized (hypox) and intact cockerels and from hypox cockerels injected with T3, purified chicken GH (cGH), and T3 plus cGH. Corticosterone in plasma and cell incubations was measured by RIA. Cellular responses to varying concentrations of steroidogenic agents were fitted and statistically analyzed by computer. Hypophysectomy reduced the basal plasma corticosterone (B) concentration to 53% of the value in intact birds and eliminated a stress response. Although hypophysectomy reduced adrenal weight by 20%, it did not change relative adrenal weight (milligrams per 100 g BW). However, replacement with cGH increased relative adrenal weight by 24%, whereas replacement with T3 or T3 plus cGH reduced relative adrenal weight by 16%. In the absence of steroidogenic agents, there were no detectable differences in B production by adrenocortical cells isolated from various experimental groups. However, with a maximal steroidogenic concentration of ACTH, B production by isolated adrenocortical cells from hypox birds was 61% of that by cells from intact birds. The ED50 of ACTH for cells from hypox cockerels was 2.7 times greater than that of cells from intact cockerels, thus indicating a loss of cell sensitivity to ACTH after hypophysectomy (the greater the ED50, the lesser the cell sensitivity). Although cGH replacement increased maximal B production (Bmax) induced by ACTH to 329% that by cells from hypox cockerels, it increased the ACTH ED50 3.6 times, thus decreasing cell sensitivity more than hypophysectomy alone. In contrast to cGH, T3 replacement maintained the cell sensitivity to ACTH at the level of cells from intact birds, but lowered Bmax to 54% that of cells from hypox cockerels. The combination of cGH and T3 administered to hypox cockerels both maintained cell sensitivity to ACTH and raised the Bmax to 358% that of cells from hypox animals. These treatments also affected 8-bromo-cAMP-induced Bmax and pregnenolone-supported Bmax, but did not significantly alter the ED50 of these agents.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 4017968 TI - Catecholestrogen regulation of prolactin synthesis in pituitary cell culture. AB - The 2-hydroxycatecholestrogens, 2-hydroxyestradiol [1,3,5-(10)estratriene-2,3,17 beta-triol] (2-OHE2) and 2-hydroxyestrone [2,3-dihydroxy-1,3,5-(10)-estratriene 17-one] (2-OHE1) were tested for their ability to alter PRL production and PRL messenger RNA (mRNA) levels in rat pituitary cell cultures. Treatment of cells with 10(-8) M 2-OHE1 or 2-OHE2 resulted in increased PRL secretion at 24 and 48 h (to 167% and 211% of control, respectively), but not at 4 h. Metabolism studies of radioactive 2-OHE1 and 2-OHE2 in parallel cultures demonstrated that the major metabolite at all times for either compound was the 2-methoxy derivative. After 24 h of treatment, nearly 40% of each compound was the original catecholestrogen, and at no time was there any detectable conversion to estradiol or estrone. Treatment of pituitary cells for 48 h with increasing concentrations of 2-OHE1 or 2-OHE2 resulted in a biphasic PRL dose response. PRL secretion was increased 3.6 fold for 2-OHE2 and 2.4-fold for 2-OHE1 between 10(-10) M and 10(-8) M. At concentrations above 5 X 10(-8) M, however, both compounds decreased PRL levels until, at 10(-6) M 2-OHE1 or 2-OHE2, PRL levels were 40-70% of control. Changes in PRL mRNA levels paralleled those of secretion. Treatment of pituitary cells with 10(-8) M of either 17 beta-estradiol (E2), 2-OHE1, or 2-OHE2 resulted in 2- to 5-fold increases in translatable and hybridizable PRL mRNA. The addition of 10(-7) M E2 plus 10(-8) M 2-OHE1 or 2-OHE2 resulted in PRL secretion and PRL mRNA levels equal to those resulting from E2 stimulation alone. The inhibition in PRL secretion and PRL mRNA levels caused by 10(-6) M 2-OHE1 or 2-OHE2 was partially overcome by coincubation of cultures with E2. Thus, 2-OHE1 and 2-OHE2 at low concentrations (less than 10(-8) M) can act on the pituitary as E2 agonists to increase PRL synthesis but at high concentrations may act as inhibitors of PRL production. PMID- 4017969 TI - Difference in the mechanism of action of alpha-adrenergic agonists and vasopressin or angiotensin II in stimulating hepatic glycogenolysis; a role of extracellular calcium concentration. AB - The role of extracellular calcium in hormone-induced glycogenolysis was examined in a rat liver perfusion system by manipulating the perfusate calcium concentration and by using calcium antagonistic drugs. When the perfusate contained 1 mM CaCl2, 5 microM phenylephrine, 20 nM vasopressin, and 10 nM angiotensin II caused a persistent increase in glucose output and phosphorylase activity as well as a transient increase in 45Ca efflux from 45Ca preloaded liver. Verapamil hydrochloride (20-100 microM) inhibited the activation of glucose output by these hormones in a dose-dependent manner. This inhibitory effect was also associated with the inhibition of hormone-induced activation of phosphorylase and 45Ca efflux. In the absence of CaCl2 in the perfusate, the glycogenolytic effect of phenylephrine and its inhibition by verapamil were obtained equally as in the presence of CaCl2. However, the effects of vasopressin and angiotensin II were markedly attenuated and were not inhibited any further by verapamil. The substitution of diltiazem hydrochloride for verapamil produced essentially identical results. Cyclic AMP concentrations in the tissue did not change under any of these test conditions. The results indicate that the glycogenolytic effect of alpha-adrenergic agonists depends on intracellular calcium but those of vasopressin and angiotensin II on extracellular calcium, and support the concept that calcium antagonistic drugs inhibit the glycogenolytic effects of calcium-dependent hormones at least by inhibiting the mobilization of calcium ion from cellular pools. PMID- 4017970 TI - Salivary testosterone concentration and testicular volume in male infants. AB - In order to investigate the changes in testicular volumes (TV) and salivary testosterone concentrations (ST) in normal male infants aged from birth to one year, TV in 158 and ST in 61 infants were measured cross-sectionally during this period. ST of normal male adolescents in Tanner's public hair stage from P2 to P5 (n = 20) were also measured as the control. To clarify the relationship between remarkable height increase and testosterone (T) during early male infancy, longitudinal follow-up of 10 male infants (4 from birth to 4 months, 6 from birth to 7 months) were also carried out by simultaneous measurement of ST and crown heel length. Maximum TV (ml) was observed at 1-4 months (1.7 +/- 0.6) (mean +/- SD) and was significantly higher than the values at birth (0.5 +/- 0.1, P less than 0.01) and at 6-12 months of age (1.4 +/- 0.4, P less than 0.01). Maximum St (ng/dl) was also observed at 1-4 months, with the mean value being 3.4 +/- 1.5, which was significantly higher than 1.9 +/- 0.8 at 6-12 months (P less than 0.01). The ST at four month was not significantly different from that at Tanner's pubic hair stage P2. The longitudinal study showed that the rise in ST was concomitant with the maximum increase in crown-heel length at 1-4 months. The fluctuations in ST and height increase were also apparently synchronous during the first year. PMID- 4017971 TI - A serum-free culture of the neurons in the septal, preoptic, and hypothalamic region. Effects of triiodothyronine and estradiol. AB - Serial modifications of Bottenstein and Sato' serum-free hormone-supplemented medium resulted in a new promising medium (1 : 1 mixture of L15 and MCDB 104 containing several supplements) for culturing neonatal rat brain cells. This medium favored the morphological and biochemical differentiation of the neurons, including particular types of cholinergic and cholinoceptive neurons, obtained enzymatically from the septum, preoptic area, and hypothalamus. On the other hand, the growth of non-neuronal cells was markedly suppressed in this medium. Therefore, their effects on the neurons are minimized in this culture. Effects of triiodothyronine (T3) and estradiol (E2) on the activities of choline acetyltransferase (ChAT) and acetylcholinesterase (AChE), synthetic and degradative enzymes for acetylcholine, respectively, were examined in this culture. The optimal concentrations of T3 and E2 for AChE activity were around 1 nM and 10 pM, respectively. However, E2 appeared to be somewhat inhibitory at higher concentrations. Although the activity of ChAT was maximum around 10 pM of E2, the ChAT activity increased as the concentration of T3 was increased to 100 nM. PMID- 4017972 TI - Productivity of immunoreactive prolactin (IR-PRL) by the human decidual explants: a new sampling method. AB - In the present study, we used an explant culture system of the human decidual tissues involving a new sampling method for investigating the productivity of immunoreactive prolactin (IR-PRL) for a 5 day period in labored and nonlabored deliveries. The maximal release of IR-PRL in the incubation medium for each 24 hour interval was achieved from the 2nd to the 3rd day of culture in both groups, which was 145.2 +/- 14.0 ng/ml/10 mg w.w. (mean +/- s.e.; n = 7) in the labor group and 101.5 +/- 16.3 ng/ml/10 mg w.w. (mean +/- s.e.; n = 4) in the nonlabor group. The release of IR-PRL in both groups was not significantly different for the first 3 days. However, the amount of IR-PRL released in the nonlabor group was 50 to 70% of that of the labor group. The tissue content of IR-PRL in both groups ranged between 3.0 and 5.0 ng/ml/10 mg w.w. From these results, it was concluded that 1) our explant culture system for the human decidual tissues produced considerably more IR-PRL than those previously reported and 2) productivity of IR-PRL was lower in nonlabored delivery than in labored delivery and 3) since the tissue content of IR-PRL for each 24 hour interval was very small, it should be strongly emphasized that the production and release of IR-PRL takes place simultaneously in the human decidual tissues. PMID- 4017973 TI - Measurement of urinary steroid profile in patients with adrenal tumor as a screening method for carcinoma. AB - Results of measurement of urinary steroid metabolite profile using gas chromatographic analysis in eight patients with adrenocortical tumors, i.e. 3 adenomas with Cushing's Syndrome, one adenoma with virilization, one adenoma without clinical manifestations, one carcinoma with Cushing's syndrome and virilization, one carcinoma with Cushing's syndrome and feminization, and one carcinoma without endocrinological symptoms, are reported. A unique pattern dominated by 5 beta and 11 beta-hydroxy steroid metabolites was confirmed in five patients with Cushing's syndrome consisting of three cases with adenomas and two with carcinomas. Excessive 3 alpha, 17 alpha, 21-trihydroxy-5 beta-pregnan-20-one (tetrahydro-11-deoxycortisol, THS) and delta 5-pregnene-3 beta, 11 alpha, 20 alpha-triol (delta 5-pregnenetriol) values were found in all three carcinomas including a nonfunctional carcinoma. These findings would strongly suggest the tumor to be a carcinoma, although excessive excretion of THS and delta 5 pregnenetriol was detected in one patient with a large adenoma associated with virilization. One patient with carcinoma was responsive to ACTH stimulation while the remainder show almost no response to exogenous ACTH. Urinary steroid profiling using gas chromatographic analysis, especially the values for THS and delta 5-pregnenetriol, appears to be a useful method to use in detecting these steroid metabolic characteristics in patients with adrenocortical carcinoma. PMID- 4017974 TI - Sleep-related growth hormone release in thyrotoxic patients before and during propylthiouracil therapy. AB - Hyporesponsiveness of GH to insulin-induced hypoglycemia has previously been reported in hyperthyroid patients. In order to clarify the GH secretion in thyrotoxic patients, sleep-related increases in the serum GH concentration were investigated. Eight thyrotoxic females ranging in age from 7 to 15 were treated with PTU. Blood samples for measurement of GH were drawn every 15 minutes during the first few hours of sleep before and during the treatment lasting about three months. The mean maximum serum GH level before the treatment was 10.0 +/- 5.5 ng/ml (mean +/- SD); this rose to 23.2 +/- 14.6 ng/ml (P less than 0.02) during the treatment. The maximum value of more than 10 ng/ml was detected in only 3 out of the 8 patients before treatment. On the other hand, serum GH levels during PTU administration rose to above 10 ng/ml in all patients except one. It was revealed that sleep-related elevations of GH occurred early in sleep and in close association with a slow-wave EEG pattern. The results show that sleep-related GH release is low in the hyperthyroid state, but becomes significantly elevated during PTU administration. However, even in the hyperthyroid state, the sleep related secretion of GH is closely correlated with the slow-wave sleep stage as in the euthyroid condition. PMID- 4017975 TI - The metabolism of aldosterone and 3 alpha, 5 beta-tetrahydroaldosterone in the rabbit. AB - Analysis of urinary metabolites of [1, 2-3H]-aldosterone and [1, 2-3H]-3 alpha, 5 beta-tetrahydroaldosterone was performed in male rabbits. The preliminary separation of urinary metabolites was carried out by submitting these metabolites to countercurrent distribution. Further separation of each fraction thus obtained was achieved by means of DEAE-Sephadex A-25 column chromatography. The separated peak was then hydrolyzed with the enzyme and the free steroid released was identified on the basis of the mobilities of the steroid and its derivatives on paper chromatography. After the injection of [1, 2-3H]-aldosterone, a major urinary metabolite was characterized as monosulphate of 3 alpha, 5 beta tetrahydroaldosterone. In addition, a small amount of the monoglucosiduronate fraction was found in the urine. 3 alpha, 5 beta-tetrahydroaldosterone and 3 beta, 5 alpha-tetrahydroaldosterone were detected as aglycones in this fraction. After the injection of [1, 2-3H]-3 alpha, 5 beta-tetrahydroaldosterone, a similar pattern of urinary radiometabolites was observed. The close similarity between the profile of urinary metabolites of [1, 2-3H]-aldosterone and that of [1, 2-3H] 3 alpha, 5 beta-tetrahydroaldosterone suggests that the conversion of aldosterone to 3 alpha, 5 beta-tetrahydroaldosterone is needed before the conjugation processes take place. PMID- 4017976 TI - Production of anti-human thyroglobulin and anti-thyroid hormone antibodies in rabbits immunized with human thyroglobulin. AB - Two rabbits (TG-1, TG-2) were immunized with human thyroglobulin (HTg) and bled serially. Antisera were obtained at different times after the first immunization and kept separately and studied. In both rabbits production of anti-HTg, and anti thyroid hormone antibodies such as anti-thyroxine (T4) and anti-triiodothyronine (T3) antibodies was observed. Binding parameters of anti-HTg antibodies with HTg, T4, and T3 were calculated in two selected antisera (70-day and 249-day). The Scatchard's plots of these antibodies were all curve-linear and were analyzed in two components: one, higher binding constant (Ka1) and smaller binding capacity (Cap1) and the other, lower binding constant (Ka2) and larger binding capacity (Cap2). Ka1 values of anti-HTg, anti-T4, and anti-T3 antibodies in sera from TG-1 obtained from 70-day and 249-day bleeding were 1.1 X 10(10) M-1, 6.0 X 10(9) M-1. 7.9 X 10(8) M-1 and 1.7 X 10(10) M-1, 6.5 X 10(9) M-1, 1.0 X 10(9) M-1, respectively. Those from TG-2 were 1.7 X 10(10) M-1, 1.8 X 10(9) M-1, 6.4 X 10(8) M-1 and 2.0 X 10(10) M-1, 3.1 X 10(9) M-1, 1.6 X 10(9) M-1, respectively. The significance of the production of anti-HTg and anti-thyroid hormone antibodies in rabbits immunized with HTg in relation to the antigenic structure of HTg molecule was discussed. PMID- 4017977 TI - Distribution of vasopressin and oxytocin in rat brain. AB - Arginine-vasopressin and oxytocin in various portions of rat brain were determined by radioimmunoassays. The hormones were extracted from tissue samples into 0.1 N HCl and then purified partially with acetone-petroleum ether extraction. The non-equilibration method was used for the assays. In this method recovery rates of arginine-vasopressin and oxytocin were 73.0 +/- 4.4% and 75.0 +/- 3.8%, respectively. Sensitivities of the assays were 1 pg of arginine vasopressin and 0.75 pg (0.3 microU) of oxytocin per assay tube. The higher concentrations of arginine-vasopressin and oxytocin were confirmed in the hypothalamo-neurohypophyseal system, where these hormones are synthesized, transported and stored. Relatively high concentrations of these hormones, especially oxytocin, were detected in spinal cord. Amygdala, hippocampus, limbic forebrain and pineal body contained a certain amount of arginine-vasopressin (2 20 pg/mg protein). Oxytocin (1-7 pg/mg protein) was also detected in amygdala, pons and medulla oblongata, pineal body and midbrain. The low concentrations of these hormones were also found in cerebral cortex and cerebellum. PMID- 4017978 TI - The negative correlation between prolactin and ionic calcium in cord blood of full term infants. AB - Total serum calcium (Ca), ionic calcium (Ca++), phosphorus, magnesium, total protein, immunoreactive parathyroid hormone (iPTH), calcitonin (iCT) and prolactin (iPRL) were measured in 30 paired samples of cord and maternal blood obtained at term delivery. In the cord blood, the concentrations of Ca, Ca++, phosphorus, magnesium, albumin, iCT and iPRL were all higher, and the concentrations of total protein and iPTH lower than in the maternal blood. The calcium binding capacity of albumin assessed with the equation (Ca-Ca++)/albumin, was similar at a given concentration of Ca in both the maternal and fetal circulations. There was a significant positive correlation between cord Ca++ and maternal Ca or Ca++, and a significant negative correlation between Ca++ and iPRL in cord blood. These data suggest that there is an active system transporting calcium from mother to fetus through the placenta, and PRL is the only one of the three hormones which was correlated with ionic calcium values in the fetus. The negative relationship between Ca++ and iPRL in the cord blood suggests an inhibitory effect of the relative hypercalcemia on PRL secretion in the fetus. PMID- 4017979 TI - Long term treatment of congenital hypothyroidism with L-triiodothyronine: 24 year follow-up. AB - A congenital hypothyroidism complicated by ventricular septal defects which was treated with L-triiodothyronine (L-T3) alone from 1 5/12 to 25 years, is described. The patient's growth and development was satisfactory and without side effects. It suggests that L-T3 may be a safe drug for long term treatment of congenital hypothyroidism. PMID- 4017980 TI - Endoscopic gallstone extraction following hydrostatic balloon dilatation of stricture in the common bile duct. AB - A patient with long-standing biliary complaints and a previous cholecystojejunostomy, reputed to be suffering from primary biliary cirrhosis was, on endoscopic retrograde cholangiography (ERC), found to have several large gallstones proximal to a stenosis in the common bile duct. After endoscopic papillotomy (EPT), and endoscopic hydrostatic dilatation of the stricture, the gallstones were successfully removed by means of an endoscopic stone extractor. After 15 months the patient remains well, with no complaints, and with completely normal liver function tests. PMID- 4017981 TI - Endoscopic findings in a case of Kaposi's sarcoma with involvement of the large and small bowel. AB - A case of Kaposi's sarcoma in underlying acquired immunodeficiency syndrome (AIDS) with involvement of the colon and the terminal ileum is presented. The endoscopic and histological findings are described and the technical and clinical aspects of the results discussed. PMID- 4017982 TI - Ergotamine-induced colitis. AB - We report on a 45-year-old woman with ulcerative colitis of the rectum that arose after the use of up to 6 suppositories of a preparation containing ergotamine daily over a period of 6 years. On the basis of a review of the literature the clinical, endoscopic and histological features of the ergotamine-induced colitis are characterized. PMID- 4017983 TI - The tRNA cycle and its relation to the rate of protein synthesis. AB - With the aid of a kinetic model, we have investigated how the adaptation between the various components of the tRNA cycle and the codon frequencies affects the rate of protein synthesis. Depending on the relative amounts of total tRNA, synthetase and ribosomes, the optimal correlations vary between a situation where all tRNA species are either present in equal amounts or are present in amounts proportional to the square-root of the corresponding codon frequencies, and a situation where the amounts of the different tRNA species present are linearly proportional to the codon frequencies. PMID- 4017984 TI - Asbestos-induced decomposition of hydrogen peroxide. AB - Decomposition of H2O2 by chrysotile asbestos was demonstrated employing titration with KMnO4. The participation of OH radicals in this process was delineated employing the OH radical scavenger dimethyl sulfoxide (DMSO). A mechanism involving the Fenton and Haber-Weiss reactions as the pathway for the H2O2 decomposition and OH radical production is postulated. PMID- 4017985 TI - Health effects of airborne effluents released from the nuclear cycle. AB - Current trends in regulations governing radioactive release from the nuclear cycle and their relationship with population dose and population health damage evaluation are discussed. It is shown that, at least in some cases, current methods may not grant a correct population-dose evaluation. A procedure to better evaluate population doses from gaseous effluents is outlined. It leads to a very simple first approximation expression which is independent of the dispersion area. Two examples, 85Kr and 222Rn, are worked out in order to give first-order evaluations of the population-dose commitment and the related risk. Strong discrepancies between the results and current evaluations are found and discussed. PMID- 4017986 TI - A study of pregnancy outcome in a small area around a chemical factory and a chemical dump. AB - Pregnancy outcome was studied in three parishes situated around a chemical factory from which air and water pollution was considered to have occurred. Data on health variables were mainly obtained from registries supplemented with hospital record information. No definite reproductive hazards could be demonstrated but an unusually high perinatal death rate among twins born in the area was noticed. The paper discusses principles involved in the design of a study of this type. PMID- 4017987 TI - Ozone-related fluorescent compounds in mouse liver and lung. AB - Groups of ten female, weanling mice were fed a basal, vitamin E-deficient diet or a basal diet supplemented with RRR-alpha-tocopheryl acetate for 14 months. During the last month one group from each dietary regimen was exposed for 30-60 min/day to 1.5 ppm ozone (25 hr total ozone exposure) and the remaining groups to control ambient air. The liver and lung tissues were homogenized and extracted with 2:1 chloroform:methanol and water. The water-soluble and organic solvent-soluble fluorescent materials were separated on Sephadex G-25 and LH-20 columns, respectively. Excitation and emission wavelengths for the eluting fractions were determined by continuous emission scans from 250 to 600 nm for each excitation wavelength between 250 and 500 nm (in increments of 25 nm). Ozone exposure did not effect the concentration of any of the fluorescent materials examined in the lung, but it resulted in a significant increase in two of four water-soluble compounds in the liver with excitation wavelength maxima/emission wavelength maxima of 270 nm/310 nm and 275 nm/350 nm (smaller molecular weight material) suggesting in vivo lipid oxidation. PMID- 4017988 TI - Influence of selenium on the metabolism of bromobenzene and a possible relationship to its hepatotoxicity. AB - When male Sprague-Dawley rats were treated with sodium selenite (1 mg/kg, sc) 24 hr prior to or simultaneously with bromobenzene (2.5 mmol/kg, ip) and sacrificed 48 hr after the bromobenzene dose, increased levels of the activities of serum transaminases (serum glutamic-oxaloacetic transaminase (SGOT) and serum glutamic pyruvic transaminase (SGPT) induced in the bromobenzene-treated rats were significantly reduced in the presence of selenium. However, no such reduction in the transaminases activities were observed when rats were either pretreated with selenite for 48 hr or pretreated with 0.1, 0.2, or 0.5 mg/kg of selenite. Although selenium alone had no effect on the hepatic microsomal drug metabolism, simultaneous treatment of selenite (1 mg/kg) with bromobenzene resulted only an increase in the activity of aniline hydroxylase after 48 hr as compared to that in the bromobenzene-treated group. When rats were given 2.5, 10, and 20 ppm of selenite in drinking water daily for 4 weeks prior to an ip injection of 2.5 mmol/kg of bromobenzene and were sacrificed 48 hr after bromobenzene administration, a reduction in the SGOT activities in all the pretreated groups and a reduction of SGPT activity in 20 ppm selenite-treated group were observed when compared with those in the bromobenzene-treated groups. A dose-dependent increase in hepatic GSH concentrations were observed due to such chronic selenium treatment. Treatment with selenite (1 mg/kg) 24 hr prior to bromobenzene injection (2.5 mmol/kg) increased initially both o and p-bromophenols in the rat urine at 0-7.5 hr without affecting urinary thioethers. On the contrary, the ratio of thioethers to p-bromophenol was significantly higher in both 2.5 and 10 ppm selenite-pretreated (4 weeks) rats as well as a significant increase in the ratio of thioethers to total phenolic metabolites in 10 ppm and an increase close to significant in 2.5 ppm selenite-treated rats were observed initially at 0-7.5 hr urine samples. These results indicate that acute selenium pretreatment under certain conditions, favors increased hydroxylation of the intermediate bromobenzene epoxides, whereas higher detoxification of the epoxides involving hepatic glutathione (GSH)/GSH transferases pathway is more favored due to increased biosynthesis of GSH in certain chronic selenium treated rats. PMID- 4017989 TI - Nature of dichlorvos intoxication in a freshwater prawn, Macrobrachium lamarrei (H. Milne Edwards). AB - Exposure of freshwater prawn (Macrobrachium lamarrei (H. Milne Edwards) to a lethal dose (96-hr LC50;0.78 mg/l) of dichlorvos for 24, 48, 72, and 96 hr induced inhibition in acetylcholinesterase and alkaline phosphatase activities and enhanced acid phosphatase activity. Hepatic glycogen values were depleted while the blood glucose level was increased up to 72 hr of exposure. After 96 hr of dichlorvos exposure hypoglycemia was recorded. The possible role of these changes in the dichlorvos intoxication is discussed. PMID- 4017991 TI - Mineral particles, mineral fibers, and lung cancer. AB - The total fibrous and nonfibrous mineral content of the lung has been analyzed in a series of 14 men with lung cancer but no history of occupational dust exposure, and in a series of 14 control men matched for age, smoking history, and general occupational class. The lung cancer patients had an average of 525 +/- 369 X 10(6) exogenous mineral particles and 17.4 +/- 19.6 X 10(6) exogenous mineral fibers/g dry lung, while the controls had averages of 261 +/- 175 mineral particles and 4.7 +/- 3.2 X 10(6) mineral fibers/g dry lung. These differences are statistically significant for both particles and fibers. Kaolinite, talc, mica, feldspars, and crystalline silica comprised the majority of particles of both groups. Approximately 90% of the particles were smaller than 2 micron in diameter and approximately 60% smaller than 1 micron; the mean particle size in the cancer group was 1.1 +/- 0.2 micron and in the control group 1.3 +/- 0.2 micron. In both groups, patients who had smoked more than 35 pack years had greater numbers of particles than patients who had smoked less than 35 pack years. It is concluded that, in this study, lungs from patients with lung cancer had statistically greater numbers of mineral particles and fibers than lungs from controls, and that smoking influences total long-term retention of particles from all sources. PMID- 4017990 TI - Effects of exposure of blood hemoglobin to nitric oxide. AB - The effect of oxygen exposure on nitrosylhemoglobin of whole human blood or its buffered solution has been determined. The amount of methemoglobin formed was determined by an anaerobic modification of the Evelyn-Malloy method; 59% of the total hemoglobin of whole blood was oxidized to methemoglobin in the first 15 min of the oxygen exposure and 78% of the total hemoglobin was oxidized after 120 min of oxygen exposure. Similar results were obtained when nitrosylhemoglobin buffered solutions were exposed to the oxygen of the air. A comparison of the present in vitro results with these obtained by injecting nitric oxide into the rat peritoneal cavity and its implications are discussed. PMID- 4017992 TI - Recovery of the murine mononuclear phagocytic system following chronic exposure to cadmium. AB - Consistent with our previously reported findings, chronic ingestion of cadmium chloride in drinking water by mice caused a decrease in the rate of circulation clearance of 51Cr-labeled sheep red blood cells (E) and IgG-coated E (E-IgG) due to a decrease in the localization of E and E-IgG in the liver. These decreases reached their nadirs after 15 weeks of cadmium ingestion and remained relatively constant for up to one year during continued ingestion of cadmium. Replacement of the drinking water containing cadmium with regular tap water resulted within 8 days in an improvement in the ability of the mice to clear E and E-IgG. Mice also had a decreased ability to develop delayed-type hypersensitivity reactions while being given cadmium; this abnormality also returned toward normal after withdrawal of cadmium. The return of these two responses toward control levels occurred while there was still a large organ burden of cadmium that was not measurably different from that at cessation of cadmium ingestion. PMID- 4017993 TI - The tissue disposition of zinc and copper following repeated administration of cadmium and selenium to rats. AB - Female rats were divided into four groups of five rats each including one control group (C). The animals were administered Na2SeO3 (Se), (CdCl2 Cd), and Na2SeO3 + CdCl2 (Cd + Se). Sodium selenite was given intragastrically at a dose of 0.5 mg Se/kg every day and cadmium chloride was injected subcutaneously every other day at a dose of 0.3 mg Cd/kg for 2 weeks. Exposure of rats to Cd caused an increase in the concentration of copper in the kidneys, blood, and liver and a decrease in the lung, but increased the concentration of zinc in the liver and brain and diminished it in the muscles and bones. In animals exposed to Se an increase in the copper concentration was observed in blood and brain; zinc was increased in the blood, heart, brain, and stomach, but decreased in the kidneys. Exposure of rats to Cd + Se resulted in an increase of copper in the kidneys and a decrease in the spleen, lungs, stomach, muscles and bones. Se prevented the cadmium induced diminution of the zinc levels in the muscles and bones. PMID- 4017994 TI - Constant rate exposure of pregnant hamsters to arsenate during early gestation. AB - We have examined the teratogenic and embryotoxic effects of constant-rate exposure of pregnant hamsters to arsenate by means of subcutaneous implants of osmotic minipumps. Different total exposure regimens were established by varying the duration of minipump implants and by varying the concentration of arsenate in the minipumps. Dams were killed on Day 13 of pregnancy, 5 days after the critical stage of organogenesis. Numbers of resorptions, dead fetuses, and living fetuses were obtained. Fetal weights, crown-rump lengths, and the incidence of malformations were recorded. Control animals were treated identically with minipumps containing demineralized water. The percentage of malformations per litter, a direct measure of teratogenesis, was dependent only upon the concentration of arsenate in the minipumps. The minimum teratogenic response was achieved with a dose of 70 mumol/kg dam/24 hr during the critical stages of organogenesis. The embryotoxic (fetotoxic) indicators, fetal weight and crown rump length, decreased with increases in exposure time and with increased concentrations of arsenate. The resorption rate also depended directly upon duration of exposure and concentration of arsenate in the minipump. PMID- 4017996 TI - Controlled exposures of volunteers with chronic obstructive pulmonary disease to sulfur dioxide. AB - Twenty-four volunteers with chronic obstructive pulmonary disease (COPD) were exposed to sulfur dioxide (SO2) at 0, 0.4, and 0.8 ppm in an environmental control chamber. Exposures lasted 1 hr and included two 15-min exercise periods (mean exercise ventilation rate 18 liter/min). Pulmonary mechanical function was evaluated before exposure, after initial exercise, and at the end of exposure. Blood oxygenation was measured by ear oximetry before exposure and during the second exercise period. Symptoms were recorded throughout exposure periods and for 1 week afterward. No statistically significant changes in physiology or symptoms could be attributed to SO2 exposure. Older adults with COPD seem less reactive to a given concentration of SO2 than heavily exercising young adult asthmatics. This may be due to lower ventilation rates (i.e., lower SO2 dose rates) and/or to lower airway reactivity in the COPD group. PMID- 4017995 TI - Effects of cadmium ingestion and food restriction on energy metabolism and tissue metal concentrations in mallard ducks (Anas platyrhynchos). AB - The single and combined effects of cadmium ingestion and food restriction were examined in a 42-day experiment with male, juvenile mallard ducks. A 2 X 3 factorial design was employed consisting of two levels of food supply (ad libitum and 55% of ad libitum intake) and three levels of cadmium in the food (0, 5, or 50 micrograms Cd/g food). Cadmium ingestion alone had no effect on body or tissue weights, liver glycogen, plasma concentrations of glucose, urea, uric acid, nonesterified fatty acids (NEFA), triiodothyronine (T3), thyroxine (T4), or plasma or adrenal concentrations of corticosterone. The food restriction resulted in reduced body weights and reduced weights of livers, kidneys, and testes, increased adrenal weights, reduced liver glycogen, increased plasma NEFA concentrations, reduced plasma T3 and T4 concentrations, and increased adrenal corticosterone concentrations. In combination with the food restriction, cadmium ingestion further reduced plasma T3 concentrations and a similar trend was noted for T4. Additionally, the highest plasma NEFA concentrations and highest plasma and adrenal concentrations of corticosterone were observed in food-restricted ducks receiving the highest level of dietary cadmium. These results suggest the ability of cadmium ingestion to enhance food restriction-induced alterations in energy metabolism at levels of dietary cadmium that are by themselves without apparent effect. Also, cadmium ingestion resulted in increased kidney concentrations of copper and zinc; this effect on kidney zinc concentrations was increased in food-restricted ducks. PMID- 4017997 TI - Toxicity of sodium fluoride to the postnatally developing rat kidney. AB - The adult rat kidney is an important target organ for sodium fluoride; however, the toxicity of fluoride to the developing kidney is unknown. This study examined renal function following NaF exposure during the first 4 weeks after birth. Sprague-Dawley rats received a single ip injection of 0, 30, or 48 mg/kg NaF on postnatal Day 1, 8, 15, or 29. Alterations in renal function, histology, and morphology were determined 24, 48, and 120 hr after exposure. Measurements of renal function included urine volume, osmolality, the ability to concentrate urine during water deprivation, urinary pH, and chloride content. Rats were then sacrificed and their kidneys processed for observation by light microscopy. Some minor alterations in renal function were observed in the three youngest age groups after NaF exposure. These changes included decreased body weight after treatment with 30 or 48 mg/kg NaF but increased kidney-body weight ratio in the 48 mg/kg group on Day 1; decreased urinary pH in both dose groups after treatment on Day 1 or 8; increased urinary volume 120 hr after treatment on Day 8; and decreased chloride excretion in the 48 mg/kg group 24 hr after injection on Day 1. None of these effects was severe. In contrast to these results, marked renal toxicity was observed in postweaning rats treated on Day 29. The NaF exposure resulted in increased kidney weight and kidney/body weight ratio, profound diuresis, decreased urinary osmolality, and decreased ability to concentrate urine during water deprivation. Urinary chloride excretion was decreased for the first 2 days after NaF exposure, then increased in water-deprived rats 120 hr after treatment. Glucosuria and hematuria were present for 2 days after treatment with 48 mg/kg. Histological lesions were apparent in the proximal tubules of the treated Day 29 rats. Thus, the kidney of the suckling rat is largely unresponsive to NaF toxicity. Renal sensitivity increases abruptly after weaning in the Day 29 rat. PMID- 4017998 TI - Determination of total and hexavalent chromium in bile after intravenous administration of potassium dichromate in rats. AB - Total and hexavalent chromium were measured in bile samples obtained from cannulated bile ducts of male rats iv administered with potassium dichromate at various doses corresponding to 0.1, 0.5, and 1 mg of chromium. The evaluation of the hexavalent form was performed by separation with a liquid anion exchanger and electrothermal atomization-atomic absorption spectrophotometric determination. Within 2 hr 1.35-2.23% of the chromium injected was recovered in bile as total chromium, the hexavalent form accounting for less than 1% of the total chromium collected, which seems almost entirely excreted as trivalent chromium. Since Cr(VI) administered iv was quickly reduced to Cr(III) in blood, the possibility exists for chromium in trivalent form to penetrate into the liver cells and to be excreted in the bile, possibly by binding to a carrier such as the low-molecular weight substance described by Yamamoto et al. (A. Yamamoto, O. Wada, and T. Ono, Toxicol. Appl. Pharmacol. 59, 515, 1981). PMID- 4017999 TI - Seeking urgent pediatric treatment: factors contributing to frequency, delay, and appropriateness. AB - The present study explored the factors that contribute to mothers' decisions to seek urgent medical attention for their children when symptoms are not of a traumatic nature. One hundred mothers seeking treatment for their children at a prepaid clinic completed a questionnaire eliciting their expectations regarding the course of their children's problems, seriousness of the problems, perceived responsibility for the symptoms, and extent to which a variety of factors contributed to their decisions to seek treatment. Demographic data and information about each child's symptoms and medical history were also obtained. Four major "reasons for seeking treatment" factors were identified: family history of the presenting complaint, worry regarding the symptoms, situational variables, and the extent of the child's illness behavior. The appropriateness of the visit, delay in seeking treatment, and frequency of mothers' use of the pediatric clinic were predicted by the nature of the presenting symptoms (particularly the presence of fever), the ages of the mother and child, and two of the reasons for seeking treatment factors (i.e., family history and child's illness behavior). The present study suggests that mothers pay more attention to presenting symptoms and to the children's behavior than to psychosocial stressors in deciding to seek urgent care. PMID- 4018000 TI - Occupational stress, social support, and depression. AB - A model of occupational stress, social support, locus of control, and depression among family physicians was developed. Two hundred and ten family physicians were administered measures of occupational stress, social support, locus of control, and depression. The hypothesized model was evaluated using structural equation models (LISREL). Results indicate that occupational stress exerts a direct effect on depression. This relationship is moderated directly by family social and emotional support and indirectly by the influence of locus of control on family social support. Support from peers was not significantly related to depression. Findings suggest that individuals with a strong sense of personal control also possess beneficial support systems in the presence of stressful situations. PMID- 4018001 TI - Prescribing drugs to men and women. AB - This article examines how often physicians prescribe therapeutic drugs to men and women who present the same complaints or receive the same diagnoses. Data are from the 1975 National Ambulatory Medical Care Survey and pertain to visits made by U.S. adults to office-based physicians that year. For most common complaints and diagnoses, women receive prescriptions more often than men do. The differences are on the small side (1 to 18% more of women's visits result in prescriptions than men's), but they are very persistent across a wide variety of health problems. Medical differences between men and women patients do not explain this. Controlling for medically relevant factors (patient age, seriousness of the problem, presence of an illness/injury or not, prior visit status, acute vs. chronic problem), the sex differences persist. Women are especially likely to get prescriptions during visits for weight gain/obesity and visits classed as observation without need for further care. The results suggest that psychosocial factors may help explain why women receive prescriptions more often during office visits than men do. Those factors could stem from patient behaviors such as overt requests for drug therapy or from physician behaviors such as sex-biased prescribing. PMID- 4018002 TI - Common-sense models of illness: the example of hypertension. AB - Our premise was that actions taken to reduce health risks are guided by the actor's subjective or common-sense constructions of the health threat. We hypothesized that illness threats are represented by their labels and symptoms (their identity), their causes, consequences, and duration. These attributes are represented at two levels: as concrete, immediately perceptible events and as abstract ideas. Both levels guide coping behavior. We interviewed 230 patients about hypertension, presumably an asymptomatic condition. When asked if they could monitor blood pressure changes, 46% of 50 nonhypertensive, clinic control cases said yes, as did 71% of 65 patients new to treatment, 92% of 50 patients in continuing treatment, and 94% of 65 re-entry patients, who had previously quit and returned to treatment. Patients in the continuing treatment group, who believed the treatment had beneficial effects upon their symptoms, reported complying with medication and were more likely to have their blood pressure controlled. Patients new to treatment were likely to drop out of treatment if: they had reported symptoms to the practitioner at the first treatment session, or they construed the disease and treatment to be acute. The data suggest that patients develop implicit models or beliefs about disease threats, which guide their treatment behavior, and that the initially most common model of high blood pressure is based on prior acute, symptomatic conditions. PMID- 4018003 TI - Components of type A, hostility, and anger-in: further relationships to angiographic findings. AB - In a previous study of patients undergoing angiography at Duke University Medical Center, we reported that of all components of the Type A behavior pattern (TABP), only Potential for Hostility and Anger-In were significantly associated with extent of coronary artery disease (CAD). The present study was undertaken to replicate these findings using a different patient population. Tape-recorded structured interviews from 125 angiography patients at Massachusetts General Hospital were blind scored using the component scoring system employed in the Duke study. The results confirmed our previous findings. Global TABP was completely unrelated to extent of CAD, while Potential for Hostility and Anger-In were significant independent predictors of disease severity. These findings argue for a reconceptualization of the manner in which the TABP is defined and assessed. PMID- 4018004 TI - Selective cardiovascular effects of stress and cigarette smoking in young women. AB - In an earlier study, we found that men who smoked a cigarette and then engaged in a mildly stressful activity (video game) evidenced pronounced increases in heart rate and blood pressure, which were approximately equal to the sum of the effects produced by either smoking alone or stress alone. In the present study, a 2 (smoke vs. sham smoke) X 2 (stress vs. no stress) factorial design was used to evaluate the impact of stress and smoking on the cardiovascular responses of young women. The results revealed that the combination of stress and cigarette smoking produced blood pressure and heart rate responses that were larger than the additive effects of smoking and stress taken separately. PMID- 4018005 TI - The type A behavior pattern, physical fitness, and psychophysiological reactivity. AB - Joint effects of the Type A behavior pattern and aerobic fitness were examined with regard to heart rate (HR) and blood pressure (BP) changes elicited by laboratory challenges. Sixty-one college students were classified as Type A or B using the Structured Interview (SI), and as physically fit or sedentary using self-reports of activity level and estimated VO2max values obtained on a step test. Subjects were challenged with the SI, presentation of a snake, mental arithmetic, a cold pressor task, and two competitive card games. Significant A-B differences were found only on the SI and the card games. During the SI: As displayed significantly greater BP increases than Bs; sedentary subjects showed greater BP increases than fit subjects; and sedentary As revealed greater BP increases than either fit As, fit Bs, or sedentary Bs. In contrast, during the competitive games, physically fit As showed reliably greater BP increases than either sedentary As, sedentary Bs, or fit Bs. Since the physically fit subjects were almost exclusively varsity athletes and the sedentary subjects were college students who reported following a sedentary lifestyle, the differences between sedentary and fit groups may have been due to differences in aerobic fitness or to the improved ability of competitive athletes or those engaged in fitness training to match arousal level to task requirements. PMID- 4018006 TI - Prognostic risk assessment in primary breast cancer by behavioral and immunological parameters. AB - Although findings from recent animal studies suggest that behavioral factors such as "helplessness" play a role in cancer progression, very few such studies with humans have been carried out. The study investigated the predictive power of an immunologic effector cell, the natural killer (NK) cell, as well as selected psychological and demographic factors, to breast cancer prognostic risk status. It was found that NK activity predicted the status of cancer spread to the axillary lymph nodes. Patients who had low levels of NK activity were rated as well-adjusted to their illness; patients who had higher NK activity appeared to be distressed or maladjusted. These findings are discussed in the light of recent animal findings linking environmental stress and behavioral responsiveness to biological vulnerability via endocrine and immune pathways. PMID- 4018008 TI - Job process charts and man-computer interaction within Naval command systems. PMID- 4018007 TI - Whole-body vibration: exposure time and acute effects--experimental assessment of discomfort. PMID- 4018009 TI - Sleep and sleepiness following a behaviourally 'active' day. PMID- 4018010 TI - Experiments on wrist deviation in manual materials handling. PMID- 4018011 TI - Sleep deprivation, chronic exercise and muscular performance. PMID- 4018012 TI - The force-velocity relation and intra-abdominal pressure during lifting activities. PMID- 4018013 TI - Hours at work at sea: watchkeeping schedules, circadian rhythms and efficiency. PMID- 4018014 TI - Heart-rate response to forest harvesting work in the south-eastern United States during summer. PMID- 4018015 TI - Load on knee joint and knee muscular activity during machine milking. PMID- 4018016 TI - Ankle joint load and leg muscle activity in various working postures during machine milking. PMID- 4018017 TI - Cognitive performance during simulated deep-sea diving. PMID- 4018018 TI - Handle positions in a holding task as a function of task height. PMID- 4018019 TI - Do TV pictures help people to remember the weather forecast? PMID- 4018020 TI - Metabolic, cardiovascular and spinal strain of a representative fuel replenishment task. PMID- 4018021 TI - A re-evaluation of the minimum altitude at which hypoxic performance decrements can be detected. PMID- 4018022 TI - Effects of local vibration transmitted from ultrasonic devices on vibrotactile perception in the hands of therapists. PMID- 4018023 TI - Structure and expression of the human haptoglobin locus. AB - Human genomic clones of the haptoglobin Hp1F and the "haptoglobin related' gene (Hpr) have been isolated. The two genes are adjacent, spanning a region of approximately 21 kb. A comparison of their coding sequences shows that Hpr differs from Hp1F at 28 codons. Northern blot and primer elongation analyses with human liver RNA show that the haptoglobin gene Hp1F appears to be transcribed some 1000-fold less in fetal than in adult liver. In adult liver the amount of Hpr mRNA is at the lower limit of detection, therefore the extent of its expression is at most less than 1000-fold that of the Hp1F gene. No Hpr mRNA can be detected in fetal liver. PMID- 4018024 TI - Inbred and wild mice carry identical deletions in their E alpha MHC genes. AB - Several inbred strains and a certain percentage of wild mice bear a deletion in the E alpha gene of the mouse major histocompatibility complex (H-2). This mutation prevents transcription of the E alpha gene and hence functional expression of the E alpha E beta dimer on the cell surface. Two strains were selected for a more precise localization of this deletion. BALB.B is a congenic line carrying the H-2b haplotype on the BALB/c background. CRO435 is an outbred stock derived from a wild mouse captured near Cairo, Egypt; it carries the H-2w37 haplotype including a null Ew28 alpha allele, as well as semi-lethal mutations in the H-2 linked t complex (tTuw7). From these two strains, we have isolated genomic clones that contain fragments spanning the E alpha deletion, and have sequenced the breakpoint region. The deletions in the two strains are identical, spanning 627 bp which include the promoter region and the signal peptide exon of the E alpha gene. Limited sequence comparison suggests that the Eb alpha allele of BALB.B is more closely related to the Ew28 alpha allele of CRO435 than both of these are to an E alpha-expressor allele, Ed alpha. It is therefore likely that the Eo deletions in the various inbred strains and wild mice are of the same origin, and we propose that they have been disseminated throughout the mouse population because of linkage to the t complex. PMID- 4018025 TI - Double-stranded DNA induces the phosphorylation of several proteins including the 90 000 mol. wt. heat-shock protein in animal cell extracts. AB - Double-stranded DNA (dsDNA) induces the transfer of phosphate from ATP to several proteins in extracts of widely divergent eukaryotic cells. Extracts of HeLa cells, rabbit reticulocytes, Xenopus eggs and Arbacia eggs all show dsDNA dependent protein phosphorylation. The mechanism is specific for dsDNA and will not respond to either RNA or single-stranded DNA. One of the proteins which is phosphorylated in response to dsDNA has a subunit mol. wt. of 90 000 and has been identified as a heat-shock protein (hsp90). Although mouse cell extracts were shown to contain hsp90, they failed to show a dsDNA-dependent protein phosphorylation. The observation that dsDNA can modulate the phosphorylation of a set of proteins raises the possibility that dsDNA may play a role as a cellular regulatory signal. PMID- 4018026 TI - Genes 55, alpha gt, 47 and 46 of bacteriophage T4: the genomic organization as deduced by sequence analysis. AB - The nucleotide sequence of T4 genes 55, alpha gt, 47 and 46 was determined by a combination of 'classical' procedures and a shotgun approach. Small DNA fragments generated by frequent cleavage with restriction enzymes or by sonication of restriction fragments were cloned in phage M13 vectors and sequenced by the dideoxy method. The positions of the genes were determined by marker rescue between the corresponding T4 amber mutants and the cloned T4 DNA fragments used in the sequencing experiments. The sequence gives an insight into the organization of this 7.1-kb early region of the T4 genome and shows that genetically 'silent' portions within this region are not void of genetic information. PMID- 4018027 TI - Structural differences between brain beta 1- and beta 2-tubulins: implications for microtubule assembly and colchicine binding. AB - Brain beta 1- and beta 2-tubulins are the major and minor beta-tubulin components of chordate brain tissue, respectively. Two cysteines of beta 1, but not beta 2, can be specifically cross-linked with the bifunctional sulfhydryl reagent N,N' ethylenebis(iodoacetamide) (EBI). They are in positions 239 and 354. Although separated by 115 amino acid residues along the beta 1-chain, the two sulfur atoms are maximally 9 A apart in the beta 1 tertiary structure. The failure of beta 2 to form a similar cross-bridge is due to the absence of a cysteine in position 239. At least 10 other sequence differences are also present between beta 1 and beta 2. Positions 239 and 354 of beta 1 probably occupy a key part of the tubulin molecule. The microtubule assembly inhibitors colchicine and podophyllotoxin appear to bind on or near this site and EBI is a potent inhibitor of microtubule assembly. Furthermore, the beta 1-cysteine in position 239 appears to be the most reactive in brain tubulin under the given conditions. The marked difference between beta 1 and beta 2 in this critical region suggests that they may have different functions in brain tissue. PMID- 4018028 TI - The Leishmania receptor for macrophages is a lipid-containing glycoconjugate. AB - The glycoconjugate of Leishmania major recognized by the monoclonal antibody WIC 79.3 exists in two forms. The cellular form associated with the promastigote is a population of amphipathic molecules consistent with membrane insertion. In contrast, the extracellular form mainly consists of hydrophilic molecules, and probably arises by cleavage of the cellular form by an endogenous phospholipase. The hydrophilic population of extracellular glycoconjugate molecules binds specifically to macrophages but not to T or B lymphoid cells. Binding of the glycoconjugate and also intact promastigotes to macrophages in vitro is specifically inhibited by Fab fragments of WIC-79.3. These data indicate that the L. major glycoconjugate is the parasite receptor for macrophages, and hence the molecule directly involved in the initiation of infection. PMID- 4018029 TI - Secretion of a soluble class I molecule encoded by the Q10 gene of the C57BL/10 mouse. AB - The DNA sequence of the Q10 genes appears to be highly conserved amongst strains of mice and has only been found to be transcribed in the liver. An examination of the nucleotide sequence of the exon that normally encodes the transmembrane domain of class I molecules suggested that the Q10 gene encodes a secreted protein. We have established this by showing that L cells transformed with an expression vector containing the Q10 gene secrete a class I molecule which was identified with an antiserum raised against a peptide predicted by the Q10 transmembrane exon. Both the L cell-derived Q10 molecule and a class I protein immunoprecipitated from serum with this anti-peptide antiserum have mol. wts. of approximately 38 000; the Q10 molecule secreted by L cells is heterogeneous in mol. wt. This heterogeneity was drastically reduced after endoglycosidase F treatment, suggesting that Q10 molecules secreted into the serum by the liver may be glycosylated differently from those secreted by L cells. Endoglycosidase F treatment of both the L cell and serum forms of the soluble molecule yielded two products with mol. wts. of approximately 32 000 and 35 000; this is consistent with the observation that the predicted Q10 protein sequence has two potential glycosylation sites. In contrast to previous published results, the Q10 molecule reacted with rabbit anti-H-2 antisera which is consistent with its greater than 80% homology to the classical transplantation antigens. PMID- 4018030 TI - The sequence and topology of human complement component C9. AB - A partial nucleotide sequence of human complement component C9 cDNA representing 94% of the coding region of the mature protein is presented. The amino acid sequence predicted from the open reading frame of this cDNA concurs with the amino acid sequence at the amino-terminal end of three proteolytic fragments of purified C9 protein. No long stretches of hydrophobic residues are present, even in the carboxy-terminal half of the molecule which reacts with lipid-soluble photoaffinity probes. Monoclonal antibody epitopes have been mapped by comparing overlapping fragments of C9 molecule to which the antibodies bind on Western blots. Several of these epitopes map to small regions containing other surface features (e.g., proteolytic cleavage sites and N-linked oligosaccharide). The amino-terminal half of C9 is rich in cysteine residues and contains a region with a high level of homology to the LDL receptor cysteine-rich domains. A model for C9 topology based on these findings is proposed. PMID- 4018031 TI - The origin of adenovirus DNA replication: minimal DNA sequence requirement in vivo. AB - Adenovirus mini-chromosomes which contain two cloned, inverted adenovirus termini replicate in vivo when supplied with non-defective adenovirus as a helper. This system has been used to define the minimum cis acting DNA sequences required for adenovirus DNA replication in vivo. Deletions into each end of the adenovirus inverted terminal repeat (ITR) were generated with Bal31 exonuclease and the resulting molecules constructed into plasmids which contained two inverted copies of the deleted ITR separated by the bacterial neomycin phosphotransferase gene. To determine the effect of the deletion in vivo plasmids cleaved to expose the adenovirus termini were co-transfected with adenovirus type 2 DNA into tissue culture cells. The replicative ability of the molecules bearing adenovirus termini was assayed by Southern blotting of extracted DNA which had been treated with DpnI, a restriction enzyme which cleaves only methylated and therefore unreplicated, input DNA. Molecules containing the terminal 45 bp of the viral genome were fully active whereas molecules containing only 36 bp were in-active in this assay. Therefore sequences required for DNA replication are contained entirely within the terminal 45 bp of the viral genome. Thus, both the previously described highly conserved region (nucleotides 9-18) and the binding site for the cellular nuclear factor I (nucleotides 19-48) are essential for adenovirus DNA replication in vivo. PMID- 4018032 TI - Structural and functional evidence for differential promoter activity of the two linked delta-crystallin genes in the chicken. AB - There are two delta-crystallin genes (delta 1 and delta 2) in the chicken which are oriented with the same transcriptional polarity (5' delta 1-delta 2-3') and are separated by approximately 4.2 kb of DNA. Existing evidence indicates that delta 1 is very active in the embryonic lens; in contrast, delta 2 appears very inactive, if expressed at all. We have sequenced the 5' regions of delta 1 and delta 2 and tested their ability to promote chloramphenicol acetyltransferase (CAT) activity using the pSVO-CAT expression vector in transfected embryonic lens epithelia. The sequence data establish that the previously reported delta crystallin cDNAs were derived from mRNAs encoded in delta 1 and not in delta 2. The transfection experiments indicated that the delta 1 promoter is appreciably stronger than the delta 2 promoter. Interestingly, a consensus CCAAT sequence (position - 71) and two consensus viral core-enhancer-like sequences (positions - 308 and +350) are confined to the more active, delta 1 gene. delta 1 and delta 2 have similar TATA boxes (TAAAA) at positions - 28 and - 27, respectively. Exon 1 in delta 1 (35 bp) and in delta 2 (34 bp) are extremely homologous, containing just two mismatches; exon 2 in delta 1 (64 bp) and in delta 2 (51 bp) are only 56% homologous and contain the putative translation initiating codon and three encoded amino acids. Unexpectedly, intron 1 of both genes has numerous pentameric repeats present in the murine immunoglobulin heavy-chain switch regions (GAGCT, GGGGT and GGGCT). Other direct repeats were found in delta 1 and delta 2, and short homologies were noted between the chicken delta-crystallin and murine alpha A-crystallin genes. PMID- 4018033 TI - Thalassemia due to a mutation in the cleavage-polyadenylation signal of the human beta-globin gene. AB - A beta-globin gene cloned from a person with beta-thalassemia contained a T----C substitution within the conserved sequence AATAAA that forms a portion of the recognition signal for endonucleolytic cleavage and polyadenylation of primary mRNA transcripts. By Northern blot analysis a novel beta-globin RNA species, 1500 nucleotides in length, was detected in erythroid RNA. Nuclease protection studies of erythroid RNA, as well as RNA generated upon transient expression of the cloned mutant gene in HeLa cells, located the 3' terminus of this novel, polyadenylated RNA 900 nucleotides downstream of the normal poly(A) addition site, within 15 nucleotides of the first AATAAA in the 3'-flanking region of the beta-globin gene. These findings define the in vivo terminus of an elongated RNA and establish that human beta-globin transcription may extend at least 900 nucleotides 3' of the normal polyadenylation site. PMID- 4018034 TI - Cloning, sequencing and transcriptional control of the Schizosaccharomyces pombe cdc10 'start' gene. AB - The cdc10 'start' gene from the fission yeast Schizosaccharomyces pombe has been cloned by rescue of mutant function. It is present as a single copy in the haploid genome. Hybridisation of the gene to Northern blots has identified a low abundance 2.7-kb polyadenylated RNA. Study of RNA extracted from cells both entering stationary phase and undergoing synchronous cell divisions suggests that commitment to the cell cycle is not controlled by regulation of cdc10 transcript level. DNA sequence analysis of the gene has identified an open reading frame capable of encoding a protein of mol. wt. 85 400. The putative cdc10 gene product shows no significant primary structure similarity with products of other fission and budding yeast cell cycle genes, or with other protein sequences in several databases. PMID- 4018035 TI - Induction of ermC requires translation of the leader peptide. AB - ermC confers resistance to macrolide-lincosamide streptogramin B antibiotics by specifying a ribosomal RNA methylase, which results in decreased ribosomal affinity for these antibiotics. ermC expression is induced by exposure to erythromycin. We have previously proposed a translational regulation model in which erythromycin causes stalling of a ribosome, which is translating a leader peptide. Stalling causes a conformation shift in the ermC mRNA which in turn unmasks the methylase ribosomal binding site. A prediction of this translational attenuation model for ermC induction was tested by replacing the second codon of the putative ermC leader peptide coding region by TAA. As expected, the introduction of this mutation resulted in an uninducible phenotype which was suppressible by two ochre suppressor mutations in Bacillus subtilis. It is concluded that translation through the leader peptide coding region, in frame with the predicted leader peptide, is required for ermC induction. PMID- 4018036 TI - A novel virulence-associated cell surface structure composed of 47-kd protein subunits in Yersinia enterocolitica. AB - A fresh human isolate of Yersinia enterocolitica serotype 03, and its derivative that had lost the virulence-associated 46-Md plasmid, were grown under defined conditions and compared for their outer membrane protein and cell surface structure. Under these conditions, the virulent strain grown at 37 degrees C expressed one major outer membrane protein (47 kd) not present in the plasmidless strain or in either strain grown at room temperature. A 200-kd protein also seen in the same preparations was shown to be an oligomer composed of the 47-kd protein subunits. Four different electron microscopic techniques showed tack-like projections covering the surface of those bacteria that expressed the 47-kd protein. These were specifically labeled with antibody to the 47-kd protein. This surface structure appeared to mediate aggregation (auto-agglutination) of the bacteria bringing their surfaces into unusually close apposition. PMID- 4018037 TI - A Raman spectroscopic investigation of the lipid state in acetylcholine receptor rich membranes from Torpedo marmorata. AB - The lipid state in acetylcholine receptor (AcChR)-rich membranes purified from electric organ of Torpedo marmorata was studied in the temperature interval from 0 degrees C to 35 degrees C using the (C-H) stretching and (C-C) skeletal optical vibrations. The Raman spectra of AcChR-rich membranes, recorded immediately after preparation of the samples, indicate that the lipids are in a predominant triclinic crystalline lattice and do not undergo a phase transition when the temperature increases up to 35 degrees C. However, the polar groups of the lipids appear subject to temperature-induced variations. After extraction of 43-kd and other non-receptor proteins, spectra indicate an order-disorder phase transition of lipids at approximately 21 degrees C. This transition appears less cooperative than the transition of the membrane lipid extract. The role of the proteins in preservation of the crystalline state of lipids in AcChR-rich membranes is discussed. PMID- 4018039 TI - Auscultatory measurement of arterial pressure during anaesthesia: a reassessment of Korotkoff sounds. AB - The accuracy of the indirect auscultatory method, using Korotkoff sounds for determination of arterial pressures, was investigated by comparison with direct intra-arterial measurements. Eight hundred and sixty-three comparisons were made in 25 patients aged between 27 and 75 years over blood pressures ranging from 59 to 235 mmHg for systolic and 28 to 145 mmHg for diastolic. The regression equation for all systolic pressure measurements was y = 13.9 + 0.81x, and for all diastolic pressure measurements was y = 21.4 + 0.71x. Although there was a significant (P less than 0.001) correlation coefficient between direct and indirect measurements for both systolic (r = 0.93) and diastolic pressures (r = 0.79), the 95% confidence limits (+/- 22 mmHg for systolic and +/- 19 mmHg for diastolic) were very wide, reflecting the influences of observer variation and other sources of error. PMID- 4018038 TI - 2-Nitroimipramine: a photoaffinity probe for the serotonin uptake/tricyclic binding site complex. AB - [3H]2-Nitroimipramine ([3H]2-NI), a compound with high affinity for the serotonin uptake system, is shown to be an effective photoaffinity probe which incorporates covalently into membrane homogenates prepared from human platelets, as well as rat brain and liver. In all cases, [3H]2-NI preferentially incorporated into a minor membrane component of 30 kd protein, as determined by SDS-polyacrylamide gel electrophoresis and subsequent fluorography. A number of selective and general serotonin uptake inhibitors quantitatively chased labeling of the 30-kd band at nanomolar concentrations. Pharmacological characterizing agents unrelated to the serotonin uptake system generally had little effect on labeling. In platelet membranes, a broad band of approximately 35-kd protein was also labeled by [3H]2-NI, but this labeling was not inhibited by any of the selective serotonin uptake blockers. Interestingly, serotonin itself increased incorporation into the 30-kd band and selectively decreased labeling of the 35-kd band. Photolytic incorporation into the 30-kd band was of high affinity, saturable, and Scatchard analyses of irreversible labeling were linear. In contrast, Scatchard transformations of [3H]2-NI equilibrium binding saturation isotherms were markedly curvilinear. Cross-linking unlabeled 2-NI to intact platelets, followed by extensive dialysis, decreased the maximal velocity (Vmax) of platelet serotonin uptake, but did not alter the affinity (Km) of serotonin for its transport site. These results are noteworthy since current theories implicate prejunctional allosteric interactions between serotonin and imipramine at serotonergic synapses.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4018041 TI - Trigeminal glycerol rhizolysis in the treatment of tic douloureux. AB - Eleven patients suffering from trigeminal neuralgia were treated by percutaneous glycerol trigeminal rhizolysis after visualization of the trigeminal cistern with metrizamide. In 10 of 11 cases treatment was successful and the pain disappeared. The technique of the treatment is described. This form of treatment is recommended as a successful and simple method, especially in the elderly population suffering from trigeminal neuralgia. PMID- 4018040 TI - Effects of anaesthesia for caesarean section on the computerized EEG of the neonate. AB - The effects of anaesthetic techniques and drugs on 18 neonates born after elective Caesarean section were studied, employing computerized EEG. Three different groups, epidural, spinal and general anaesthesia, were compared with each other and with a control group after normal vaginal delivery. A new computerized EEG method, Zero Band Power Rate (ZBPR) analysis, was devised for this study and implemented together with conventional spectral EEG estimates of five frequency bands. ZBPR analysis was found to be much more sensitive than conventional spectral analyses for detecting differences between the study groups. Significant differences occurred between the general anaesthesia group and the epidural and control groups and also between the spinal group and the epidural and control groups. No significant difference was seen between the epidural group and the control group. Significant differences were attributed to the clinical use of two drugs: thiopentone in the general anaesthesia group and ephedrine in the spinal group. The effects of these drugs on the neonatal EEG were reflected in decreased ZBPR values, particularly during sleep. PMID- 4018042 TI - Dead space in HFV. PMID- 4018044 TI - Alignment of the human body in standing. AB - Alignment of the body in typical symmetrical standing was studied by photographing fifteen subjects in profile on a reaction board. Two aspects of alignment were studied: (1) the anteroposterior position of the body landmarks of knee joint, hip joint, shoulder joint, and ear, compared to the ankle joint; and (2) the positions of the partial centers of gravity above the knee and hip, as a measure of how the body is balanced above these joints. The knee, hip, shoulder, and ear were forward of the ankle in all subjects. On average, the knee was 3.8 (+/- 2.0), the hip 6.2 (+/- 1.3) the shoulder 3.8 (+/- 1.9), and the ear 5.9 (+/- 1.6) cm (+/-S.D.) anterior to the ankle. The positions of landmarks were positively correlated with one another but not highly. The position of the center of gravity could be predicted well from the positions of the landmarks within individual subjects' data, but not across subjects. The centers of gravity above the knee and hip were calculated by subtracting the mass and position of the segments below the joint from the whole-body center of gravity. The center of gravity above the knee was located on average 1.4 (+/- 1.1) cm in front of the joint, and that of the hip 1.0 (+/- 1.6) cm behind the trochanter. Thus, at both knee and hip in typical standing, there exist slight gravitational torques tending to extend the joints. PMID- 4018043 TI - The relationship between lactate and ventilatory thresholds: coincidental or cause and effect? AB - To determine if blood lactate (LA) is the stimulus responsible for 'breakaway' ventilation (VE), the lactate (LT) and ventilation (VT) thresholds were monitored during one-legged cycling exercise. Ten healthy volunteer male subjects (Mean 2 legged VO2max = 4.27 l X min-1) performed prior exercise (PE) to reduce muscle glycogen stores by cycling at 75-85% of maximal heart rate (HR max) for 60-75 min, followed by a 30 h low carbohydrate diet. Pre- and post- LT and VT tests were performed on a cycle ergometer employing a continuous protocol with increments of 16 W every 3 min. Muscle biopsies were taken from the vastus lateralis muscle before the PE ride, prior to the threshold test 24 h later, and before testing the non-exercised (NE) leg. An I.V. catheter placed in the antecubital vein was used for serial blood samples taken at rest, and during the final 30 s of each progressive load. Gas analysis was calculated every 30 s (Beckman Metabolic Measurement Cart). Biopsies (N = 3) showed that the exercise and diet regimen elicited glycogen reduction which significantly (p less than 0.05) reduced R and the blood LA concentration in both the PE (2.62 to 1.99 mmol X l-1) and NE (2.87 to 2.26 mmol X l-1) legs at LT. At VT, LA concentrations were also significantly reduced in the PE (3.35 to 2.56 mmol X l-1) and NE (3.59 to 2.74 mmol X l-1) legs. VO2 and VE, however, were similar between pre- and post- tests.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4018045 TI - The flexor function of the m. pronator teres in man: a quantitative electromyographic study. AB - The muscle pronator teres was studied by surface electromyography during elbow flexion in a horizontal plane. The forearm was in semi-pronation and movement was performed at various velocities. A quantitative comparison was made between pronator teres activity and two main elbow flexors, biceps brachii and brachioradialis. The mean timing of the onset of activity was constant: biceps brachii was activated first followed by pronator teres and brachioradialis, and the lower the velocity of flexion, the earlier was the onset of biceps brachii activity. There was a linear relationship between the integrated EMG from each muscle and the work done. However, this relationship was less exact for pronator teres and brachioradialis at low values of work, a finding which opens questions about the generality of this relationship and about the "muscle equivalent" concept. Pronator teres appears to participate in elbow flexion besides its role in pronation. Despite similar anatomical peculiarities, pronator teres does not behave in the same way as anconaeus or popliteus and, above all, it is not the sole muscle active in slow movement. Thus, all the stocky muscles lying close to an articulation do not behave in the same way. PMID- 4018046 TI - The influence of cardiorespiratory fitness on the decrement in maximal aerobic power at high altitude. AB - There are conflicting reports in the literature which imply that the decrement in maximal aerobic power experienced by a sea-level (SL) resident sojourning at high altitude (HA) is either smaller or larger for the more aerobically "fit" person. In the present study, data collected during several investigations conducted at an altitude of 4300 m were analyzed to determine if the level of aerobic fitness influenced the decrement in maximal oxygen uptake (VO2max) at HA. The VO2max of 51 male SL residents was measured at an altitude of 50 m and again at 4300 m. The subjects' ages, heights, and weights (mean +/- SE) were 22 +/- 1 yr, 177 +/- 7 cm and 78 +/- 2 kg, respectively. The subjects' VO2max ranged from 36 to 60 ml X kg 1 X min -1 (mean +/- SE = 48 +/- 1) and the individual values were normally distributed within this range. Likewise, the decrement in VO2max at HA was normally distributed from 3 ml X kg-1 X min-1 (9% VO2max at SL) to 29 ml X kg-1 X min-1 (54% VO2max at SL), and averaged 13 +/- 1 ml X kg-1 X min-1 (27 +/- 1% VO2max at SL). The linear correlation coefficient between aerobic fitness and the magnitude of the decrement in VO2max at HA expressed in absolute terms was r = 0.56, or expressed as % VO2max at SL was r = 0.30; both were statistically significant (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4018047 TI - Effect of trunk load on the energy expenditure of treadmill walking and ergometer cycling. AB - Data concerning the effect of trunk loads on the energy expenditure of various activities are scanty and partly conflicting. The energy expenditure of walking (4.5 km hr-1, 1.5% inclination) and ergometer cycling (60 watt, 60 rpm) was measured in 23 apparently healthy subjects with and without a trunk load of 10% of the body weight. For walking, the increment in energy expenditure per kg of load was 2.55 +/- 0.25 watt, while the increment per kg of body weight was 4.01 +/- 0.45 watt. For ergometer cycling, the increment per kg of load was 1.12 +/- 0.64 while that per kg of body weight was 2.73 +/- 0.56 watt. Prediction of energy expenditure for trunk loads has previously been made on the basis of the relation between energy expenditure and body weight. Our data show that this may lead to considerable overestimation. PMID- 4018048 TI - Thermoregulation during prolonged actual and laboratory-simulated bicycling. AB - Thermoregulatory and cardiorespiratory responses to bicycling 55 km (mean speed 9.7 m X s-1) outdoors (15 degrees C DB) were compared to equivalent cycle ergometry (90 min at 65% VO2max) in the laboratory (20-23 degrees C DB, 50% RH) in 7 trained cyclists. Outdoor environmental conditions were simulated with fans and lamps, and were contrasted with standard no-wind, no-sun laboratory conditions. Sweating rate was similar during outdoor and laboratory simulated outdoor cycling (0.90 and 0.87 to 0.94 1 X h-1 respectively). During outdoor bicycling, mean heart rate (161 bt X min-1) was 7-13% higher (p less than .05) than under laboratory conditions, suggesting a greater strain for a similar external work rate. The increase in rectal temperature (0.8 degrees C) was 33-50% less (p less than 0.05) at the cooler outdoor ambient temperature than in the laboratory. Thermoregulatory stress was greater under the no-fan, no-lamp laboratory condition than during simulated outdoor conditions (36-38% greater (p less than 0.05) sweating rate, 15-18% greater (p less than 0.01) mean skin temperature, 6.4 to 7.8 fold greater (p less than 0.01) amount of clothing retrained sweat). The cooling wind encountered in actual road bicycling apparently reduces thermoregulatory and circulatory demands compared with stationary cycle ergometry indoors. Failure to account for this enhanced cooling may result in overestimation of the physiological stress of actual road cycling.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4018049 TI - Variations in iron status with fatigue modelled from training in female distance runners. AB - A low hemoglobin level or even frank anemia is common among female endurance runners; controversy presently exists on the effectiveness of iron supplementation. In the past inadequate descriptions of training and too infrequent measurement of iron indices over a sufficiently long period, have made it difficult to establish any relationship between iron status and training upon which to base a rational iron therapy. In this study 5 young women distance runners age 18-25 years have been studied for 300 days. A numerical index was used to quantify the extent of an individual's daily training effort and a conceptual model of the effect of training allowed definition of the extent of consequent fatigue, to be calculated. Red blood cell number and hemoglobin concentration were measured regularly throughout, and during the last 200 days serum iron, ferritin, total iron binding capacity and percent transferrin saturation were also measured. It has been shown in most subjects that serum iron and transferrin saturation varied in phase with training and the fatigue index, throughout the period while serum ferritin varied out of phase. It is suggested that supplementing iron intake may be of little use during heavy training and concomitant high fatigue because transferrin saturation is also very high at this time and ineffective in promoting absorption of dietary iron. PMID- 4018050 TI - Effect of growth on muscle capillarity and fiber type composition in rat diaphragm. AB - The effect of growth on the capillarity and fiber type composition of the diaphragm, soleus and extensor digitorum longus (EDL) muscles of rats weighing between 55 and 330 g have been studied. Muscle samples obtained from the anesthetized rat were rapidly frozen and sliced transversely in a cryostat. The sections were stained histochemically by the SDH method and the myosin ATPase method after preincubation at pH 4.3 to typify fibers (FG, FOG and SO fibers). To visualize capillaries, the myosin ATPase method after preincubation at pH 4.0 was used. The percentage of FOG fibers decreased in all muscles with growth. While the FG and SO fibers increased in the diaphragm, SO fibers increased in the soleus, and FG fibers increased in the EDL. The capillary density showed a hyperbolic decrease with growth in all muscles, while the number of capillaries around each fiber increased in all muscles with growth. It is concluded that growth causes the changing properties of the motoneurons and the new capillary formation in the diaphragm muscle, as well as the soleus and EDL muscles. PMID- 4018051 TI - Increased protein degradation after eccentric exercise. AB - The purposes of these experiments were to compare the activities of glucose 6 phosphate dehydrogenase (G6PDH) and the lysosomal enzyme N-acetyl-beta glucosaminidase (NAG) in rat muscles and to assess protein degradation after eccentric exercise (running down a 18 degrees grade). The following results were obtained: (1) Muscles in which the G6PDH activity was increased also showed an increase in NAG activity that was smaller and occurred later and/or was more prolonged than the increase in G6PDH activity. (2) The urinary 3 methylhistidine/creatinine ratio was statistically elevated for 3 days after eccentric exercise and this increase was much larger and more prolonged than previously observed in rats run on the level. Taken together our results suggest that increased protein degradation after exercise is due to increased proteolysis of muscle tissue damaged during the exercise bout and that lysosomal enzymes may be involved in this degradation. PMID- 4018052 TI - Muscle glycogen depletion during exercise at 9 degrees C and 21 degrees C. AB - This study compared glycogen depletion in active skeletal muscle after light and moderate exercise in both cold and comfortable ambient conditions. Twelve male subjects (Ss) were divided into two groups equally matched for the submaximal exercise intensity corresponding to a blood lactate concentration of 4 mM (W4) during cycle exercise. On two separate days Ss rested for 30 min at ambient temperatures of either 9 degrees C or 21 degrees C, with the order of temperature exposure being counter-balanced among Ss. Following rest a tissue specimen was obtained from the m. vastus lateralis with the needle biopsy technique. Six Ss then exercised on a cycle ergometer for 30 min at 30% W4 (range = 50 - 65 W) while the remaining group exercised at 60% W4 (range = 85 - 120 W). Another biopsy was taken immediately after exercise and both samples were assayed for glycogen content. Identical procedures were repeated for the second environmental exposure. No significant glycogen depletion was observed in the Ss exercising at 30% W4 in 21 degrees C, but a 23% decrease (p = 0.04) was observed when the same exercise was performed at 9 degrees C. A 22% decrease (p = 0.002) in glycogen occurred in the 60% W4 group at 21 degrees C, which was not significantly different from that observed during the same exercise at 9 degrees C. The results suggest that muscle substrate utilization is increased during light exercise in a cold environment as compared to similar exercise at a comfortable temperature, probably due to shivering thermogenesis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4018053 TI - Creatine kinase and creatine kinase MB in endurance runners and in patients with myocardial infarction. AB - Following a 100 km race creatine kinase (CK) creatine kinase MB (CKMB) activities were serially measured in well trained athletes and compared with enzyme activities in patients with acute myocardial infarction (AMI). The half-time of disappearance of CK (CKt1/2) was 1.75 +/- 0.70 days in runners who trained within the 1st week after the race, and was 0.81 +/- 0.18 days in patients with AMI, P less than 0.005. CKt1/2 in runners was shorter (1.17 +/- 0.28 days) when no training was performed in the first postrace week. CKt1/2 was linearly correlated with age (P less than 0.01) in the runners but not in the patients. CKMBt1/2 was 1.30 and 1.11 days in two runners and 0.56 +/- 0.10 days in patients with AMI (P less than 0.05). In line with histologic and enzymatic findings in skeletal muscle of long distance runners as reported by other workers, our kinetic data provide further evidence that CK and CKMB are released from muscular compartments in runners other than those in patients with AMI. PMID- 4018054 TI - Vital capacity in trained and untrained healthy young adults in the Netherlands. AB - Slow inspiratory vital capacity was measured in 226 healthy young adults, aged from 17 to 35 years. The group included 119 men and 107 women, 87 trained subjects, 71 untrained subjects who intended to take part in a training program for competitive rowing, and 68 untrained subjects who never took part in any competitive sport. The vital capacity increased with height, weight, fat-free mass, height X fat-free mass, and height-independent fat-free mass, with men having significantly higher vital capacities than women of the same height or weight. In both males and females vital capacity showed the best relation with height X fat-free mass (correlation coefficients are 0.78 and 0.57 respectively). Multiple regression on vital capacity with height, weight, fat-free mass, height X fat-free mass, height-independent fat-free mass, percentage body fat, and age increased the correlation coefficient only slightly (0.80 and 0.59 respectively). The subjects had vital capacities that were much higher than those predicted for them by equations originating from the USA. There was no difference between the observed vital capacities and those predicted by equations originating from Europe. There is a difference in vital capacity between the European subjects studied and subjects of similar height studied in the USA. This implies that equations derived from subjects in the USA cannot be applied to European subjects. From our results we conclude that vital capacity is not increased by physical activity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4018055 TI - Force kinetics and oxygen consumption during bicycle ergometer work in racing cyclists and reference-group. AB - The forces acting on the right crank of a bicycle ergometer were measured in 18 male subjects (6 racing cyclists, 8 students of physical education, 4 long distance runners) during an incremental exercise test. Oxygen consumption (VO2) was simultaneously determined by means of a breath-by-breath method. Differences in peak values of the typical force record might indicate a different force distribution during each cranking cycle. When compared to the reference group, the racing cyclists showed peak values that were significantly lower at all levels of work load. Oxygen consumption during the initial 20 min of the test was found to be significantly lower in the cyclist group (cyclists: 37.2 +/- 3.2 1, reference group: 41.1 +/- 3.9 1). These results suggest that a different force distribution during a crank revolution might lead to an improved gross efficiency in the cyclist group. The findings might be due to different fractions of ST fibres in the exercising muscle. PMID- 4018056 TI - Plasma testosterone and catecholamine responses to physical exercise of different intensities in men. AB - Plasma testosterone, noradrenaline, and adrenaline concentrations during three bicycle ergometer tests of the same total work output (2160 J X kg-1) but different intensity and duration were measured in healthy male subjects. Tests A and B consisted of three consecutive exercise bouts, lasting 6 min each, of either increasing (1.5, 2.0, 2.5 W X kg-1) or constant (2.0, 2.0, 2.0 W X kg-1) work loads, respectively. In test C the subjects performed two exercise bouts each lasting 4.5 min, with work loads of 4.0 W X kg-1. All the exercise bouts were separated by 1-min periods of rest. Exercise B of constant low intensity resulted only in a small increase in plasma noradrenaline concentration. Exercise A of graded intensity caused an increase in both catecholamine levels, whereas, during the most intensive exercise C, significant elevations in plasma noradrenaline, adrenaline and testosterone concentrations occurred. A significant positive correlation was obtained between the mean value of plasma testosterone and that of adrenaline as well as noradrenaline during exercise. It is concluded that both plasma testosterone and catecholamine responses to physical effort depend more on work intensity than on work duration or total work output. PMID- 4018057 TI - The effect of corrective surgery on energy expenditure during ambulation in children with cerebral palsy. AB - Mechanical efficiency, heart rate, blood lactate, and some other variables were studied in six children with cerebral palsy who walked on a treadmill before and after corrective surgery. During each test, conducted at each child's naturally selected speed, two situations were studied: steady state level walking for 9 min, and then walking at an increasing inclination up to 20% for another 10 min. During the test the subjects were allowed to hold on to a handrail to eliminate the risk of falling off the treadmill. The corrective surgery resulted in a 5% reduction in oxygen consumption per kg body mass during level walking. The subjects' levels of physical fitness, as estimated from oxygen pulse, however, were unchanged. These results are indicative of a biomechanical improvement due to the corrective surgery. While walking at a 20% inclination the subjects off loaded themselves to different degrees on the handrail which influenced the results. Their feeling of exhaustion at this load was probably due to local factors, since heart rate was well below maximal values, and blood lactate, respiratory exchange ratio and ventilatory equivalent also indicated that they were below their anaerobic thresholds (50-60% of maximal oxygen uptake). PMID- 4018058 TI - The influence of clothing ensembles on the lower critical temperature. AB - This paper describes the effect of clothing insulation on the lower critical temperature (LCT). Twelve young adult females were exposed to a temperature of 10 degrees C for 2 1/2 h. LCT was estimated at five different clothing conditions according to the intersect method. The total weights of clothing ensembles (CW) of the five conditions were 0.45, 0.52, 0.82, 1.34, and 2.56 kg, and their thermal insulating values (I) were 0.44, 0.60, 0.77, 1.21, and 2.14 clo, respectively. LCT of the five clothing ensembles were estimated to be 26.4, 25.4, 23.5, 21.5, and 17.5 degrees C, respectively. The regression equation of the logarithm of LCT on CW was calculated as logLCT = 1.4469-0.08283 CW and that on I was log LCT = 1.4613-0.10526 I, respectively. The rate of changes in LCT is suggested to be dependent on the clothing conditions as for the following equations: dLCT/dCW = -5.34 exp(-0.1907 CW) or dLCT/dI = -7.01 exp(-0.2424 I). PMID- 4018060 TI - Differential heating of trunk and extremities. Effects on thermoregulation mechanisms. AB - Experiments in which the whole human body was heated or cooled are compared with others in which one extremity (arm or leg) was simultaneously cooled or heated. With a warm load on the rest of the body resulting in general sweating, a cold load on one extremity did not evoke local shivering; with general body cooling, heating one limb did not stop the shivering. Skin temperatures of the other parts of the body were not influenced by warming or cooling one extremity. Evaporative heat loss was influenced by local, mean skin and core temperature, whereas shivering did not depend on local temperature, and vasomotor control seemed to be controlled predominantly by central temperatures. A cold load on an extremity during whole body heating in most cases induced an oscillatory behaviour of core temperature and of the evaporative heat loss from the body and the extremity. It is assumed that local, mean skin and core temperatures influence the three autonomous effector systems to very different degree. PMID- 4018059 TI - Central venous pressure and plasma arginine vasopressin during water immersion in man. AB - The influence of increased central venous pressure (CVP) on the plasma concentration of arginine vasopressin (pAVP) was examined in 7 healthy males subjected to water immersion (WI) up to the neck following overnight food- and fluid restriction. During WI the subject sat upright in a pool (water temperature = 35.0 degrees C) for 6 h. In control experiments the subject assumed the same position outside the pool wearing a water perfused garment (water temperature = 34.6 degrees C). CVP increased markedly during WI and after 20 min of immersion it attained a level which was significantly higher than the control value (10.9 +/- 1.5 (mean +/- SE) vs. 2.2 +/- 1.3 mm Hg, p less than 0.01). This increase was sustained throughout the 6 h WI period. Simultaneously, after 20 min pAVP during WI was significantly lower than control values (1.8 +/- 0.3 vs. 2.2 +/- 0.3 pg X ml-1, p less than 0.05) and sustained throughout WI. Systolic arterial pressure increased significantly by 7-10 mm Hg (p less than 0.05) after 2 h of WI, while diastolic arterial pressure was unchanged. Heart rate was decreased by 10 bpm throughout immersion. There was no change in plasma osmolality when comparing control with immersion. A pronounced osmotic diuresis, natriuresis and kaliuresis occurred during WI, counteracting an acute significant increase in plasma volume of 6.5 +/- 1.9% (P less than 0.01 within 20 min of immersion). We conclude that an increase in CVP due to WI is accompanied by suppressed pAVP. PMID- 4018061 TI - Effects of training at and above the lactate threshold on the lactate threshold and maximal oxygen uptake. AB - Thirty-three college women (mean age = 21.8 years) participated in a 5 d X wk-1, 12 week training program. Subjects were randomly assigned to 3 groups, above lactate threshold (greater than LT) (N = 11; trained at 69 watts above the workload associated with LT), = LT (N = 12; trained at the work load associated with LT) and control (C) (N = 10). Subjects were assessed for VO2max, VO2LT, VO2LT/VO2max, before and after training, using a discontinuous 3 min incremental (starting at 0 watts increasing 34 watts each work load) protocol on a cycle ergometer (Monark). Respiratory gas exchange measures were determined using standard open circuit spirometry while LT was determined from blood samples taken immediately following each work load from an indwelling venous catheter located in the back of a heated hand. Body composition parameters were determined before and after training via hydrostatic weighing. Training work loads were equated so that each subject expended approximately 1465 kJ per training session (Monark cycle ergometer) regardless of training intensity. Pretraining, no significant differences existed between groups for any variable. Post training the greater than LT group had significantly higher VO2max (13%), VO2LT (47%) and VO2LT/VO2max (33%) values as compared to C (p less than .05). Within group comparisons revealed that none of the groups significantly changed VO2max as a result of training, only the greater than LT group showed a significant increase in VO2LT (48%) (p less than .05), while both the = LT and greater than LT group showed significant increases in VO2LT/VO2max (= LT 16%, greater than LT 42% (p less than .05)).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4018063 TI - Improved "active" electrodes for recording bioelectric signals in work physiology. AB - Conventional recording techniques of bioelectric signals using surface electrodes are often very sensitive to artefacts, in particular when carrying out physiological investigations in ergonomics and sports. An "active" electrode, by means of impedance-converting-amplification, was developed to reduce motion artefacts in recording of bioelectrical signals. The application of these electrodes on the skin surface does not differ from that of conventional electrodes. The circuit elements of the impedance-converting-preamplifier, including a power-supply, are placed in a small portable housing. A qualitative comparison between conventional Ag/AgCl electrodes and "active" electrodes in ECG and EMG recordings with artefact simulation shows a high degree of artefact suppression for the "active" electrodes. PMID- 4018062 TI - The force-velocity relationship of arm flexion in untrained males and females and arm-trained athletes. AB - The force-velocity curve (FVC) of arm flexion was established in 123 untrained males and 110 untrained females aged from 15 to 36 years, and 48 arm-trained athletes competing in different sport disciplines. The FVC was described by Hill's equation and defined by the parameters: maximal static moment (M0), maximal angular velocity (omega 0), maximal power (P0) and the concavity of the FVC (H). Within the given age range the level of the curve parameters of both untrained men and women was independent of age. On average, H was the same in all three groups. As compared to M0 of the untrained males, M0 of the athletes was 33% higher and M0 of the females was 38% lower; with regard to P0 these differences were +30% and -43% respectively. omega 0 was the same for trained and untrained males, whereas omega 0 of the women was 10% lower than omega 0 of the men. PMID- 4018064 TI - A comparison of the effect of external loading upon power output in stair climbing and running up a ramp. AB - Previous studies have shown that external loading increases the power output measured during stair climbing. However, it was noted in an earlier study that stairtreads form mechanical contraints which limit the extent to which a subject can be externally loaded, and, thereby, make it impossible to observe maximal power output for this type of activity. The purpose of this study was to compare the effects of external loading upon power output when running up stairs or a ramp. Since a ramp is free of the mechanical constraints of stairtreads, it was felt that higher power output values would be achieved using the ramp, and that it would be possible to observe an asymptote in power output which could not be obtained for stair climbing. Seven male subjects performed maximal ramp and stair climbing tests under five experimental loading conditions (no external load, 10.1, 19.2, 24.2, and 29.2 kg). For the ramp, it was possible to employ a sixth loading condition of 34.2 kg. For stair climbing, the mean (+/- SD) power output values under the five experimental conditions were 16.6 +/- 0.7, 17.3 +/- 1.3, 18.5 +/- 1.0, 18.6 +/- 1.5, and 18.9 +/- 1.7 W X kg-1, respectively. In contrast, the mean (+/- SD) power output values observed while running up the ramp were 18.8 +/- 1.4, 19.9 +/- 1.6, 20.5 +/- 1.6, 20.1 +/- 2.1, 20.3 +/- 2.1, and 19.8 +/ 1.9 W X kg-1, respectively. At each experimental condition, the differences between the ramp and stairs was significant (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4018065 TI - Retrospective analysis of two hundred and twelve cases of bacteremia due to anaerobic microorganisms. AB - Cases of bacteremia caused by anaerobic microorganisms and occurring during a four year period in a non-selected patient group in a Spanish general hospital were analysed retrospectively. Microbiological data was collected on 212 patients and clinical data on 103 patients. Cases of anaerobic bacteremia represented 8.6% of the total number of cases of bacteremia. Of the 232 anaerobic microorganisms causing bacteremia, gram-negative bacilli were responsible in 113 cases (48.7%), gram-positive bacilli in 92 cases (39.6%), gram-positive cocci in 25 cases (10.7%), and Veillonella spp. in two cases (0.8%). The most important clinical features were fever (64%), anemia (56%), septic shock (22%) and metastatic abscesses (21%). Patients with anaerobic bacteremia were hospitalized for an average of 51.7 days. The overall mortality was 32% and factors associated with poor prognosis were severe underlying disease, nosocomial acquisition, presence of shock, presence of metastatic foci of infection, and absence of adequate surgical drainage. The mortality rate of patients who received adequate antimicrobial therapy was 30% and that of patients who received inadequate treatment or none was 29%. It is concluded that anaerobic bacteremia has a significant rate of morbidity and mortality and that underlying disease and surgical debridement and/or drainage have greater prognostic significance than the use of antimicrobial agents. PMID- 4018066 TI - Etiology of community-acquired pneumonia in patients requiring hospitalization. AB - The etiology of community-acquired pneumonia was studied in 127 patients with roentgenologically verified pneumonia who needed hospitalization. Etiology was determined on the basis of a positive blood culture and/or a significant antibody titer increase. Streptococcus pneumoniae was the probable etiological agent in 69 patients, nontypeable Haemophilus influenzae in five patients, Streptococcus pyogenes in two patients, and Legionella pneumophila and Staphylococcus aureus in one patient each. Evidence of Mycoplasma pneumoniae infection was found in 18 patients and of Chlamydia psittaci infection in three patients. Influenza virus type A was the cause of infection in 15 patients. One patient had infection with influenza virus type B, one patient with parainfluenza virus type 1, and three patients with respiratory syncytial virus. In 20 patients there was evidence of infection with more than one microorganism. No etiological agent was found in 27 patients. Since Streptococcus pneumoniae was the predominant etiological agent penicillin should be drug of first choice in patients with pneumonia who need treatment in hospital. In young adults, however, the high frequency of Mycoplasma pneumoniae infection would justify the use of erythromycin or doxycycline as drug of first choice. PMID- 4018067 TI - Comparison of two systems for identification of anaerobic bacteria. AB - The RapID Ana and the API 20A systems for identification of anaerobic bacteria were compared for accuracy on 108 recent isolates of gram-negative and gram positive anaerobic bacteria. No additional tests or gas-liquid chromatography were used. RapID Ana identified 91.7% of the isolated strains to species level and 6.5% to genus level but failed to identify 1.8% of the total strains. API 20A identified 85.2% of strains to species level, 3.7% to genus level but failed to identify 11.1% of the total strains. Although the difference between the identification rates of the two systems was not significant, it was concluded that RapID Ana was easier to perform and interpret. PMID- 4018068 TI - Inefficacy of the commercial live oral Ty 21a vaccine in the prevention of typhoid fever. AB - The efficacy of the live oral typhoid fever vaccine Ty 21a marketed in Switzerland in 1981 was investigated. Forty-seven Swiss travellers to Third World countries contracted typhoid fever in 1982 and 1983; 20 (43%) of these persons had been vaccinated with Ty 21a. The incidence of typhoid fever in vaccinees was 1.1 per 10,000 doses of Ty 21a vaccine sold, which was similar to the incidence of 0.9 per 10,000 doses for the ineffective killed Ty 2 vaccine. Comparison of the incidence of vaccination in patients with typhoid fever in 1983 and in healthy travellers to India revealed vaccination efficacy rates which were not significantly different from zero. It is suggested that Ty 21a vaccine in the form marketed in Switzerland in 1981-1983 is not sufficiently potent or heat stable, so that the doses of viable bacteria ingested were too low. PMID- 4018070 TI - Fatal Selenomonas sputigena septicemia probably originating from lung abscess. AB - A case of fatal septicemia with Selenomonas sputigena in an immunocompromised patient is reported. The patient had a lung abscess from which the septicemia is believed to have originated. In contrast to the only other case reported in the literature, the isolate from our patient was characterized by very slow and difficult growth. PMID- 4018069 TI - Disseminated candidiasis with extensive folliculitis in abusers of brown Iranian heroin. AB - Two cases of heroin abusers who developed disseminated candidiasis are reported. Cultures of skin lesions revealed Candida albicans, which on histology were shown to be located in and around hair shafts. Both patients recovered after treatment with amphotericin B combined with 5-fluorocytosine and either ketoconazole or dexamethasone. This unusual cutaneous syndrome of candidal infection associated with extensive folliculitis seems to be related to the use of a particular type of heroin, the so-called brown Iranian heroin. PMID- 4018071 TI - Isolation of Moellerella wisconsensis from an infected human gallbladder. PMID- 4018072 TI - Emergence of multiple drug resistance among Salmonella species in Jordan. PMID- 4018073 TI - Isolation of Aeromonas species from animals. PMID- 4018074 TI - Support of the single species concept for Streptococcus milleri by DNA hybridization data. PMID- 4018075 TI - Kinetic studies on reduction of cytochromes P-450 and b5 by dithionite. AB - The kinetics of reduction of cytochromes P-450 and b5 by dithionite had been studied in solution and in microsomal and proteoliposomal membranes by the stopped-flow technique. In all the cases studied the kinetic curves of reduction of cytochrome b5 obey first-order kinetics in relation to cytochrome with the rate constant about 14 s-1 at 10.6 mM dithionite. The kinetic curves of reduction of cytochrome P-450 fit an equation for the sum of two exponentials with the parameters varying from system to system. The simple first-order kinetics of cytochrome P-450 reduction had been observed in the presence of non-ionic detergent Triton N-101. The apparent biphasity of cytochrome P-450 reduction by dithionite should be the result asymmetric distribution of hemoprotein in microsomal and proteoliposomal membranes as well as in cytochrome oligomers in solution. PMID- 4018076 TI - Mechanism of activation of bovine kidney pyruvate dehydrogenase a kinase by malonyl-CoA and enzyme-catalyzed decarboxylation of malonyl-CoA. AB - The activity of the pyruvate dehydrogenase kinase, which phosphorylates and thereby inactivates the pyruvate dehydrogenase complex, was stimulated by malonyl CoA. Treatment with [2-14C]malonyl-CoA resulted in acylation of sites in the complex. Both acylation and activation of kinase activity increased in a time dependent manner with a parallel increase in those activities when the malonyl CoA:CoA ratio was varied. Protein-bound acyl groups were labilized by performic acid treatment indicating their attachment to protein at thiol residues; however, the product released was volatile, which is not characteristic of malonic acid. While malonyl-CoA was initially free of acetyl-CoA, stimulation of kinase activity and acylation of sites in the complex by malonyl-CoA were shown to be contingent upon enzyme-catalyzed decarboxylation. Decarboxylation appeared to be catalyzed by a trace contaminant present in highly purified preparations of both the pyruvate and 2-oxoglutarate dehydrogenase complexes. Under conditions in which both free CoA was removed (by conversion to succinyl-CoA) and then, after various periods, free acetyl-CoA was removed (by enzymic conversion to acetyl phosphate), both acetylation of sites in the complex and activation of kinase activity increased in a time-dependent manner. Concomitantly there was a decrease in the concentration dependence for activation of the kinase by malonyl-CoA. Our results strongly support the conclusion that activation of kinase activity is associated with acylation of sites in the complex, and that, in the case of malonyl-CoA, those processes depend on enzyme-catalyzed decarboxylation. PMID- 4018077 TI - Hepatic carbamoyl phosphate metabolism. Role of cytosolic and mitochondrial carbamoyl phosphate in de novo pyrimidine synthesis. AB - The interrelationship between the two carbamoyl phosphate pools in intact hepatocytes and intact liver was studied with respect to de novo pyrimidine synthesis by use of selective inhibitors of the mitochondrial and the cytosolic carbamoyl-phosphate synthetase. Inhibition of mitochondrial carbamoyl phosphate synthesis by 4-pentenoate was without effect on galactosamine-stimulated pyrimidine synthesis. Conditions favouring mitochondrial carbamoyl phosphate accumulation, like excess ammonium ions or L-norvaline, led to an increase in pyrimidine synthesis bypassing the feedback inhibition of cytosolic carbamoyl phosphate synthetase by UTP. A stimulation of pyrimidine synthesis was not observed when the carbamoyl phosphate accumulation was due to aspartate deficiency in the presence of aminooxyacetate. The full response of pyrimidine synthesis to excess ammonium ions was restored, even in the presence of aminooxyacetate, when aspartate was substituted. This is explained by an inhibition of aspartate carbamoyltransferase flux [in view of the Km (aspartate = 0.7 mmol/l) of this enzyme] resulting from a 90% decrease in aspartate tissue levels. Acivicin, the inhibitor of cytosolic carbamoyl-phosphate synthetase, completely abolished the galactosamine-induced stimulation of pyrimidine synthesis, but was without effect on the stimulation of pyrimidine synthesis by ammonium ions and L-norvaline. It is concluded that experimental changes in mitochondrial carbamoyl phosphate content exert effects on de novo pyrimidine synthesis; however, it is considered unlikely that relevant amounts of mitochondrial carbamoyl phosphate are used for pyrimidine synthesis under physiological conditions. In addition the data point to a potential regulatory role of aspartate in hepatic pyrimidine synthesis. PMID- 4018078 TI - Role of plasma albumin in renal elimination of a mercapturic acid. Analyses in normal and mutant analbuminemic rats. AB - Biosynthesis of N-acetylcysteine S-conjugates of xenobiotics (mercapturic acids) occurs via interorgan metabolism and the renal transtubular transport system plays an important role in elimination of the final metabolites from the organism. To assess the behavior of a mercapturic acid in the circulation, plasma clearance of radioactive S-benzyl-N-acetylcysteine and its interaction with plasma proteins were studied in normal and mutant analbuminemic rats (NAR). Intravenously injected S-benzyl-N-acetylcysteine rapidly disappeared from the circulation both in NAR and normal animals. However, its plasma clearance was significantly higher in NAR (45.7 ml kg-1 min-1) than in normal rats (25.2 ml kg 1 min-1). Ultrafiltration analysis revealed that 18.4% and 80.1% of the mercapturate bound to plasma protein(s) from NAR and normal rats, respectively, at 50 microM ligand concentration. The mercapturic acid bound to plasma albumin with an association constant of 2.24 X 10(5) M-1 and the number of binding sites was 1.18/mol albumin. The binding was competitively inhibited by probenecid and L tryptophan. Concomitant administration of this mercapturic acid with equimolar amounts of albumin resulted in a marked decrease in the plasma clearance (26.2 ml kg-1 min-1) and an increase in the urinary secretion of this ligand in NAR. 30 min after injection of the mercapturic acid (10 mumol/kg body weight), 27.3% and 60.4% of the injected dose was recovered from urine and kidneys of NAR and normal rats respectively. About 41% of the dose was recovered in NAR urine when the ligand was injected bound to an equimolar amount of albumin. These results suggested that albumin is important for the renal accumulation and urinary elimination of the circulating mercapturic acid. PMID- 4018079 TI - Creatine phosphokinase: isoenzymes in Torpedo marmorata. AB - Creatine phosphokinase (ATP: creatine N-phosphotransferase, EC 2.7.3.2) is the major constituent of the "low-salt-soluble" proteins of the electric organ from Torpedo marmorata. The denatured subunits of the enzyme have an apparent Mr of 43 000 and isoelectric points ranging between pH 6.2 and pH 6.5. Identical properties are found for the creatine phosphokinase from Torpedo muscle tissue. Anti-(electric organ creatine phosphokinase) antibodies are specific for the muscle-type enzyme and do not cross-react with enzymes present in Torpedo brain and electric lobe tissue. Biochemical and immunochemical properties of the enzyme associated with acetylcholine-receptor-enriched membranes show that this enzyme is as the "low-salt-soluble" electric organ enzyme of the muscle-specific type. In vitro translation of electric organ poly(A)-rich mRNA in a reticulocyte lysate reveals the abundance of mRNA specific for muscle creatine phosphokinase. During embryonic development of the electrocyte a continuous increase of translatable amounts of this mRNA is observed. No brain-type polypeptides are synthesized. The subunits of the brain-specific enzyme differ in molecular mass (Mr approximately equal to 42000) and isoelectric properties (pI approximately equal to 7.0-7.2). The unexpected finding that the brain forms are more basic than the muscle specific enzyme is supported by agarose and cellulose acetate electrophoresis and ion-exchange chromatography properties. PMID- 4018080 TI - Properties of cytosolic epoxide hydrolase purified from the liver of untreated and clofibrate-treated mice. Characterization of optimal assay conditions, substrate specificity and effects of modulators on the catalytic activity. AB - We have characterized certain catalytic properties of cytosolic epoxide hydrolases purified from untreated and clofibrate-treated mouse liver. The enzyme activity was found to be sensitive to oxygen, but nitrogen-saturated buffers containing dithiothreitol maintained high activity for at least 12 h at 0 degrees C. Linearity of the hydration of trans-stilbene oxide with time and protein was established, the pH optimum was broad (6.5 to 7.4) and the temperature optimum was close to 50 degrees C for both forms. The activity was independent of ionic strength, with the exception of the control form in the absence of dithiothreitol, where a lower activity was observed at low ionic strength. The activity decreased when ethanol was replaced by acetone or acetonitrile as solvent for the substrate. Tetrahydrofuran was found to be highly inhibitory, while dimethylsulfoxide had less pronounced effects. The apparent Km values were 4.9 microM, 73 microM and 1980 microM for the control form with trans-stilbene oxide, cis-stilbene oxide and styrene oxide as substrates, respectively. The Km values for the enzyme from clofibrate-treated mice were in the same range, although the V values were higher for all three substrates with this form. The highest turnover was found for trans-beta-propylstyrene oxide as substrate, followed by trans-beta-ethylstyrene oxide. Little or no activity was observed with benzo[a]pyrene 4,5-oxide or cholesterol 5,6 alpha-oxide. The enzymes were found to be sensitive to 5,5'-dithiobis(2-nitrobenzoic acid) and a phenylmercuric salt. alpha-Naphthoflavone, beta-naphthoflavone and chalcone derivatives also inhibited the activity, while none of the compounds known to activate microsomal epoxide hydrolase activated the cytosolic forms. PMID- 4018081 TI - Hysteretic behaviour of citrate synthase. Isotopically chiral citryl-CoA reveals increased number of reversals of the synthase condensation step under steady state conditions. AB - Citrate specimens derived from chiral acetates were converted to the CoA derivatives. These were reconverted with citrate synthase to citrates under conditions of either predominating hydrolytic burst or predominating steady-state period. The stereochemical purity of substrates and products was determined. Reversal of the synthase condensation step occurs under both conditions but is markedly increased during the steady-state period. The results indicate that citryl-CoA-derived acetyl-CoA and oxaloacetate create the steady-state conditions. The hydrolase state and the ligase/lyase state of the synthase predominate under burst and steady-state conditions, respectively. This result indicates a conversion of the hydrolase state into the ligase/lyase state during the transition. PMID- 4018082 TI - Differentiation of rat myoblasts. Regulation of turnover of ribosomal proteins and their mRNAs. AB - The regulation of ribosomal proteins (r-proteins) and their mRNAs (rp-mRNAs) was studied in the L6 myoblast, a mammalian cell line which can undergo myogenesis. Upon terminal differentiation, the rate of accumulation of mature ribosomes dropped to approximately 25% of the rate found in undifferentiated myoblasts. Despite the drop in the rate of ribosome accumulation and the rate of rRNA synthesis following terminal differentiation, the rate of r-protein synthesis remained constant. The excess r-protein synthesized in myotubes was quickly degraded. The levels of rp-mRNAs were assessed before and after differentiation. Over 90% of the rp-mRNAs were found on polysomes in both myoblasts and myotubes and represented similar fractions of total poly(A)-rich mRNA. The half-lives of the rp-mRNAs averaged approximately 11 h in both myoblasts and myotubes. In vitro nuclear transcription measurements of a representative rp-mRNA (L32 mRNA) revealed that following differentiation, its rate of synthesis relative to the overall transcription rate dropped by approximately 26% in myotubes while the rate of transcription of rRNA dropped by approximately 77%. These results indicate that the coordination of r-protein and rRNA synthesis observed in myoblasts was uncoupled in myotubes at the level of transcription. PMID- 4018083 TI - Bundling of microtubules by glyceraldehyde-3-phosphate dehydrogenase and its modulation by ATP. AB - Glyceraldehyde-3-phosphate dehydrogenase from different origins (brain, muscle, erythrocytes) binds to microtubules polymerized from pure brain tubulin and causes bundle formation in vitro. ATP is shown to dissociate these bundles into individual microtubules, while the dehydrogenase is not displaced from the polymers by this nucleotide. ATP can be replaced by adenosine 5'-(beta, gamma imido]triphosphate, a nonhydrolyzable analog of ATP. These data are interpreted in terms of dissociation of the glyceraldehyde-3-phosphate dehydrogenase tetramer into dimers by ATP. The enzyme is also efficiently purified by a tubulin Sepharose affinity chromatography. PMID- 4018084 TI - Identification of the calmodulin-binding components in bovine lens plasma membranes. AB - Lens membranes, purified from calf lenses, have been labeled by covalent cross linking to membrane-bound 125I-calmodulin with dithiobis(succinimidyl propionate). Electrophoretic analysis in sodium dodecyl sulfate demonstrated two major 125I-containing products of Mr = 49 000 and 36 000. That the formation of these two components was specifically inhibited by unlabeled calmodulin, or calmodulin antagonists, would indicate that the formation of these components was calmodulin-specific. The size of these two 125I-labeled components was unchanged over a range of 125I-calmodulin or dithiobis(succinimidyl propionate) concentrations indicating that they represent 1:1 complexes between 125I calmodulin (Mr = 17 000) and Mr-32 000 and Mr-19 000 lens membrane components respectively. Although formation of both cross-linked components exhibited an absolute dependence on Mg2+, the autoradiographic intensity of these components was enhanced when Ca2+ was included with Mg2+ during the cross-linking reaction. Labeling was maximal in 10 mM MgCl2 and approximately 1 microM Ca2+. Treatment of lens membranes with chymotrypsin resulted in the cleavage of MP26 (the major lens membrane protein), with the appearance of a major proteolytic fragment of Mr = 22 000. This proteolysis was not associated with any significant change in either the size or amount of the 125I-calmodulin-labeled membrane components. These results suggest that calmodulin interacts with two membrane proteins, but not significantly with MP26, in the intact lens cell membrane. Our results indicate the need to maintain caution in interpreting direct calcium plus calmodulin effects on MP26 and lens cell junctions. PMID- 4018085 TI - The mechanism of the C-13(3) esterification step in the biosynthesis of bacteriochlorophyll a. AB - 5-Aminolaevulinate labelled with 18O at its C-1 carboxy oxygen atoms was prepared and incorporated into bacteriochlorophyll aphytyl of Rhodopseudomonas sphaeroides and bacteriochlorophyll ageranylgeranyl of Rhodospirillum rubrum. The biosynthetic samples of the bacteriochlorophylls were separately processed to obtain their isoprenyl alcohol components from the C-17(3) ester linkages and methanol from the C-13(3) methoxycarbonyl group. Methods were developed for the quantification of the isotopic composition of the various alcohols (methanol, phytol, geranylgeraniol). It was shown that the hydroxyl oxygen atoms of all the three alcohols originated from one of the C-1 oxygen atoms of the precursor 5 aminolaevulinate. In the light of these results the in vivo mechanism for the O methylation reaction at C-13(3) during the biosynthesis of the two species of bacteriochlorophylls is discussed. PMID- 4018086 TI - Nucleotide sequence of cucumber mosaic virus RNA. 1. Presence of a sequence complementary to part of the viral satellite RNA and homologies with other viral RNAs. AB - The nucleotide sequence of the 3389 residues of RNA 1 (Mr 1.15 X 10(6) of the Q strain of cucumber mosaic virus (CMV) was determined, completing the primary structure of the CMV genome (8617 nucleotides). CMV RNA 1 was sequenced by the dideoxy-chain-termination method using M13 clones carrying RNA 1 sequences as well as synthetic oligonucleotide primers on RNA 1 as a template. At the 5' end of the RNA there are 97 noncoding residues between the cap structure and the first AUG (98-100), which is the start of a single long open-reading frame. This reading frame encodes a translation product of 991 amino acid residues (Mr 110791) and stops 319 nucleotide residues from the 3' end of RNA 1. In addition to the conserved 3' region present in all CMV RNAs (307 residues in RNA 1), RNAs 1 and 2 have highly homologous 5' leader sequences, a 12-nucleotide segment of which is also conserved in the corresponding RNAs of brome mosaic virus (BMV). CMV satellite RNA can form stable base pairs with a region of CMV RNAs 1 and 2 including this 12-nucleotide sequence, implying a regulatory function. This conserved sequence is part of a hairpin structure in RNAs 1 and 2 of CMV and BMV and in CMV satellite RNA. The entire translation products of RNA 1 of CMV and BMV could be aligned with significant homology. Less prominent homologies were found with alfalfa mosaic virus RNA 1 translation product and with tobacco mosaic virus Mr-126000 protein. PMID- 4018087 TI - Steady-state and time-resolved fluorescence anisotropy study of phospholipid molecular motion in the gel phase using 1-palmitoyl-2-[9-(2-anthryl)-nonanoyl] sn-glycero-3-phosphocholine as probe. AB - 1-Palmitoyl-2-[9-(2-anthryl)-nonanoyl]-sn-glycero-3-phosphocholine (Anthr-PC), a non-perturbing phospholipid probe [de Bony, J. and Tocane, J. F. (1983) Chem. Phys. Lipids 32, 105-121], has been designed in order to obtain insight into the membrane lipid organization at a 'microscopic' level, in terms of lateral distribution both in model and in natural membranes [de Bony, J. et al. (1984) Eur. J. Biochem. 143, 373-379; FEBS Lett. 174, 1-6]. In the present study, the molecular motions of this new fluorescent probe embedded in a lipid matrix have been investigated by fluorescence anisotropy techniques in steady-state and time resolved modes. The results indicate that long axis rotation, monitored by the out-of-plane mode of rotation of the fluorophore, is fast even in the phospholipid gel state. It is moderately sensitive to the phase transition. The data suggest that this rotation is anisotropic. Cholesterol exhibits little effect on this rotation. The rotation of the long axis itself is sensitive to the transition. It is hindered as inferred from measurements at wavelength where both the in-plane and out-of-plane motions contribute to the depolarization of the emitted fluorescence light. Cholesterol restricts this motion. The behaviour of the free 9-(2-anthryl)-nonanoic acid is not significantly different from that of Anthr-PC. These results are discussed with respect to the influence of orientational constraints on the photodimerization process when this lipid probe is used to monitor phospholipid lateral distribution. PMID- 4018088 TI - Primary structure of the two variants of a sperm-specific histone H1 from the annelid Platynereis dumerilii. AB - The amino acid sequences of the two variants (H1a 121 residues and H1b 119 residues) of the sperm-specific histone H1 from the polychaete annelid Platynereis dumerilii have been completely established. Comparison of the sequences of these two variants shows one deletion of two residues in histone H1b and 22 substitents, of which most occur in the globular domain. The two variants differ highly in a sequence of nine residues adjacent to the conservative phenylalanine residue of histone H1 (64-72 in H1a, 62-70 in H1b) which makes H1a less hydrophobic than H1b. The small molecular size of Platynereis H1a and H1b is a unique feature among the histones H1 of which the size ranges between 189 residues (chicken erythrocyte H5) and 248 residues (sea urchin sperm H1). H1a and H1b have short N- and C-terminal basic domains but the size of the globular domain (approximately equal to 80 residues) is similar to that of other H1s. In the globular region the variant H1a exhibits a close relationship with somatic or sperm H1s whereas the variant H1b is more related to H5 histones. PMID- 4018089 TI - Regulation of the human-erythrocyte hexose-monophosphate shunt under conditions of oxidative stress. A study using NMR spectroscopy, a kinetic isotope effect, a reconstituted system and computer simulation. AB - The regulation of the hexose monophosphate shunt of human erythrocytes under conditions of oxidative stress has been investigated by monitoring the reduction of oxidised glutathione (GSSG) to reduced glutathione (GSH) in erythrocytes containing high levels of GSSG; 1H NMR and a biochemical assay were used to measure the changes. A reconstituted metabolic system prepared with the purified erythrocyte enzymes was used in conjunction with studies of intact cells and haemolysates to determine the dependence of the rate of GSH production on the activities of hexokinase and glucose-6-phosphate dehydrogenase. Both of these enzymes have previously been claimed to be the rate-limiting step of oxidatively stimulated flux through the hexose monophosphate shunt. The absence of a kinetic isotope effect on the rate of GSH production in these systems, when [1-2H]glucose replaced glucose as the source of reducing equivalents, showed that glucose-6 phosphate dehydrogenase activity was not a strong determinant of the flux. The dependence of the rate of GSH production on the concentration of the hexokinase inhibitors glucose 1,6-bisphosphate and glycerate 2,3-bisphosphate showed that, under conditions of oxidative stress, hexokinase was the principal determinant of flux through the shunt. Glucose 1,6-bisphosphate at the concentration present in vivo appears to be more important in limiting hexokinase activity, and thus the rate of glucose utilisation, than was previously assumed. A detailed computer model of the system was developed based on the reported kinetic parameters of the enzymes involved. A sensitivity analysis of this model predicted that the hexokinase reaction would have a sensitivity coefficient of 0.995 with respect to the maximal rate of GSH production. PMID- 4018090 TI - Evidence for two oxygen-linked binding sites for polyanions in dromedary hemoglobin. AB - The functional properties of dromedary hemoglobin have been studied as a function of chloride, polyphosphates and pH and compared with those of human hemoglobin. The two proteins have the same amino acid residues at the anion-binding sites as well as at the level of the groups responsible for the alkaline Bohr effect. Analysis of the experimental data reveals that: (a) intrinsic oxygen affinity and the Bohr effect are very similar for the two proteins; (b) the association equilibrium constants of chloride are substantially higher in the dromedary system, both in the unligated and ligated state; (c) two polyanion-binding sites occur in dromedary oxy and deoxyhemoglobin; (d) association constants of polyphosphates for the higher-affinity binding site (probably in the cavity between beta chains) are comparable for the two proteins under physiological conditions; association constants for the second binding site in dromedary hemoglobin are not affected by pH changes; (e) the dependence of oxygen affinity in dromedary hemoglobin upon chloride concentration is complex, this anion at relatively low concentrations reverses the effect of millimolar polyphosphate; (f) both in stopped-flow and flash photolysis experiments the kinetic behaviour of dromedary hemoglobin is consistent with the equilibrium results. The pronounced sensitivity to solvent composition of the functional properties of dromedary hemoglobin even in the oxy state stresses the potential relevance of this conformation for regulating the oxygen transport in vivo. PMID- 4018091 TI - Cell-free synthesis and co-translational processing of the human asialoglycoprotein receptor. AB - The human asialoglycoprotein receptor is a 46-kDa membrane glycoprotein. It is initially synthesized as a 40-kDa precursor species possessing two N-linked high mannose oligosaccharides which is subsequently converted to the 46-kDa mature product upon modification of its oligosaccharides of the complex form [Schwartz, A. L. & Rup, D. (1983) J. Biol. Chem. 258, 11 249-11 255]. To investigate further the biosynthesis of the human asialoglycoprotein receptor, we have utilized a cell-free wheat germ translation system supplemented with dog pancreatic microsomal membranes and programmed with HepG2 and human liver RNA. The primary translation product of the human receptor is a single 34-kDa species and this species is expressed throughout human fetal and adult development. The primary translation product possesses no cleavable signal peptide and is cotranslationally glycosylated to form the 40-kDa precursor species. In addition, the human asialoglycoprotein receptor is co-translationally inserted into microsomal membranes such that a 4-kDa cytoplasmic tail is susceptible to trypsin digestion. PMID- 4018092 TI - Assembly of oligonucleosomes into a limit series of multimeric higher-order chromatin structures. AB - Chicken erythrocyte chromatin, obtained after fragmentation with micrococcal nuclease, appears to remain folded in a stable distribution of supranucleosomal structures in buffers containing 80 mM NaCl. These supranucleosomal particles are composed of on average 25 nucleosomes. However, the integrity of the linker DNA within these particles is not required. The supranucleosomal particles have been interpreted by others as superbeads cut out of a preexisting granular nominal 30 nm chromatin fibre. We show that the same distribution of supranucleosomal structures (even those containing internal DNA scissions) can be reconstituted from unfolded nuclear chromatin extracts as present in 10 mM or 600 mM NaCl. Moreover, fractions of oligonucleosomes with mean lengths between 6 and 15 nucleosomes reassemble or aggregate into a limit series of multimeric species. The existence of an assembly barrier could be inferred as we were unable to observe a stable and soluble assembly product containing more than about 25 nucleosomes. We propose an alternative explanation for the generation and observation of a constant distribution of supranucleosomal structures in nuclear extracts, based on the assembly or aggregation property of oligonucleosomes and on the existence of an assembly barrier. PMID- 4018093 TI - Isolation of proteins assembled in lipid body membranes during fat mobilization in cucumber cotyledons. AB - Lipid bodies from fat-mobilizing cotyledons of cucumber and other Cucurbitaceae were investigated. Proteins and glycoproteins were analyzed by electrophoresis and then used to characterize the lipid body membrane at different stages of cell development. Contaminations by other membranes or organelles were ruled out by comparing the main constituents from the endoplasmic reticulum, cytosol, glyoxysomes and protein bodies with the pattern of the lipid body membrane, considering both the prevalent peptides and the dominating glycoproteins. Among the proteins of lipid body membranes in ripening and germinating cotyledons, a 90 kDa peptide was found as unique marker of lipid bodies at the stage of fat mobilization. The 90-kDa protein was purified, and antibodies against it were raised in rabbits. By means of immunoprecipitation and electrophoretic analysis it was demonstrated that the synthesis of the 90-kDa form located in lipid bodies shows a transient increase and subsequent decline, with maximal values being observed at day 3 of germination. At this stage, the rate of de novo synthesis was compared considering lipid body proteins and other organellar proteins. The 90-kDa protein appeared as the lipid body constituent that is synthesized and assembled in the organelle by far at the highest rates. PMID- 4018094 TI - A microanalytical procedure for determination of the base composition of DNA. AB - A new procedure for the determination of the percentage guanine plus cytosine (% G+C; mol/100 mol) values of microquantities of DNA is described. Its principle is a DNA-polymerase-I-directed nick translation of DNA in the presence of dGTP, dTTP, [3H]dCTP, and [alpha-32P]dATP. Kinetics experiments indicate that the plateau value is reached in about 20 min of incubation under our experimental conditions. Percentage G+C is obtained from the linear relation 1/(% G+C) = 0.01 K [32P]/[3H] + 0.01, where the ratio of trichloroacetic-acid-precipitable radioactivity is taken into account, the K value being determined for each experiment by using a few reference DNAs of known composition. This procedure has proven suitable for analysis of plasmidic, viral and cellular DNAs of different base composition (25-75% G+C), shape (linear and circular double-stranded DNA) and size (100-150 000 base pairs). Usual methods for % G+C analysis (buoyant density and melting temperature determinations) yield unreliable results in the presence of either modified or unusual bases: the double-labeling procedure is still valid under these conditions. The latter is, therefore, the method of choice for analysis or rare DNA species which are available in very small quantities (it requires amounts of DNA as low as 1 ng, i.e. several order of magnitude lower than those used for chromatographic analysis of DNA hydrolysates). Since the obtention of highly purified DNA is an essential prerequisite for the double-labeling procedure, a method for purification of bacterial DNA is detailed in the present work. PMID- 4018095 TI - The complete primary structure of ribosomal proteins L1, L14, L15, L23, L24 and L29 from Bacillus stearothermophilus. AB - The amino acid sequences of ribosomal proteins L1, L14, L15, L23, L24 and L29 from Bacillus stearothermophilus have been completely determined. This has been achieved by sequence analyses of peptides derived from enzymatic digestions of the proteins with trypsin, chymotrypsin, pepsin, Staphylococcus aureus protease, and Armillaria mellea protease as well as by chemical cleavage with hydroxylamine and cyanogen bromide. Based on the primary structures of the six proteins, their secondary structures were predicted using four different computer prediction programs. A comparison of the amino acid sequences of the studied proteins from B. stearothermophilus with the homologous proteins from Escherichia coli revealed that in four proteins (L1, L15, L24 and L29) between 40-50% of the residue in the sequences are identical, whereas this value is significantly higher (69%) for L14 and lower (28%) for L23. The distribution of those amino acid residues which are identical in the corresponding proteins from the two bacteria is not random along the protein chain: some regions are highly conserved whereas others are not. This finding indicates that the regions which are conserved during evolution are important for the spatial structure and/or function of the protein. PMID- 4018096 TI - The amino acid sequence of wheat histone H2A(1). A core histone with a C-terminal extension. AB - The complete amino acid sequence (145 residues) of histone variant H2A(1) from wheat germ Triticum aestivum cultivar T4 has been established from Edman degradation of large overlapping fragments. The sequence of histone variant H2A(1) differs from the homologous calf histone in 61 amino acid positions. These differences include an extension of H2A(1) by 19 amino acids at its carboxyl end. PMID- 4018097 TI - Immunochemical analysis of rough and smooth microsomes from rat liver. Segregation of docking protein in rough membranes. AB - Docking protein (or signal recognition particle receptor) is an integral membrane protein essential for translocation of nascent polypeptides across the membrane of the endoplasmic reticulum. It serves as the receptor for the signal recognition particle, and represents the site of interaction between the translation and the translocation systems. Results presented here demonstrate that this protein is localized exclusively in rough microsomal membranes. Rough and smooth microsomes were prepared and their content of various marker proteins was determined by immunochemical techniques. Whereas a number of proteins, including cytochromes b5 and P-450 and their reductases were evenly distributed between rough and smooth microsomes, docking protein was found at 20-fold higher levels in the rough fraction. On the basis of these results it is concluded that docking protein is a functionally characterized integral protein specifically restricted to rough microsomal membranes. PMID- 4018099 TI - Fractionation of newly replicated nucleosomes by density labeling and rate zonal centrifugation for the analysis of the deposition sites of newly synthesized nucleosomal core histones. AB - We have found that partial resolution of newly replicated nucleosomes can be achieved by rate zonal centrifugation through sucrose density gradients preformed in heavy water. Nucleosome samples were obtained from MH-134SC cells density labeled with 5-iododeoxyuridine in the presence of suitable isotopic precursors. The method is simple and can be performed under conditions that do not destabilize the nucleosome structure. This gave us an exciting opportunity to study the deposition sites of newly synthesized histones. Nucleosomes were obtained from cells pulse-labeled simultaneously with 5-iododeoxyuridine and [3H]lysine for the rate zonal analysis. Proteins in the resulting fractions were resolved by sodium dodecyl sulfate/polyacrylamide gel electrophoresis, and visualized by silver staining and fluorography. The distribution of newly synthesized H2A and H2B coincided closely with that of bulk nucleosomes. The distribution of newly synthesized H3 and H4 was shifted to the bottom sides of the bulk nucleosome peaks, but not so far as to the putative peaks of newly replicated (dense) nucleosomes. This means that newly synthesized histones are deposited on DNA in disproportionate amounts and that their sites of deposition are not restricted to newly replicated DNA. PMID- 4018098 TI - The occurrence of two immunologically distinguishable beta-glucocerebrosidases in human spleen. AB - The beta-glucosidase activity in spleen from control subjects and patients with different clinical phenotypes of Gaucher's disease was characterized. The occurrence of a soluble non-specific beta-glucosidase with a neutral pH optimum and two membrane-associated beta-glucocerebrosidases with an acid pH optimum was demonstrated. The two beta-glucocerebrosidases can be distinguished on the basis of their ability to react with anti-(placental beta-glucocerebrosidase) antibodies bound to protein-A--Sepharose 4B beads. One of the splenic beta glucocerebrosidases (form I) is precipitated by the immobilized antibodies and the other (form II) is not. The two forms also differ in binding affinity to concanavalin A, degree of stimulation of enzymic activity by taurocholate and isoelectric point. In contrast, the Km values of the two beta-glucocerebrosidases for natural and artificial substrates are similar and both are inhibited by conduritol B-epoxide. In spleen from three patients with type 1, one patient with type 2 and one patient with type 3 Gaucher's disease form I beta glucocerebrosidase was found to be clearly deficient, whereas the activity of form II was 25-50% of that in control spleen. The non-specific, neutral beta glucosidase was not deficient in these Gaucher spleens. The distinct biochemical and immunological properties of non-specific beta-glucosidase and the fact that normal levels of the enzyme are present in patients with Gaucher's disease indicate, in confirmation of previous reports, that non-specific beta-glucosidase is not related to beta-glucocerebrosidase. PMID- 4018100 TI - Serum bile acids and their conjugates in breast-fed infants with prolonged jaundice. AB - Serum bile acids and their conjugates were analysed in 20 breast-fed infants with prolonged jaundice. The mean total bile acid levels in serum were increased in the breast-fed infants with jaundice, as compared with those in either breast- or bottle-fed infants without jaundice. However, there were no significant differences between the groups. All the breast-fed infants examined, regardless of association with jaundice, had a bile acid pattern dominated by taurine conjugates (the ratio of glycine- to taurine-conjugated bile acid, G/T ratio, less than 1.00). In contrast, the bottle-fed infants without jaundice had a pattern dominated by glycine conjugates (G/T ratio, more than 1.00). Among the breast-fed infants with jaundice, the mean G/T ratio in those who had serum bilirubin levels over 10 mg/100 ml was significantly lower than that in those who had serum bilirubin levels of less than 10 mg/100 ml. The altered bile acid metabolism might be associated with the pathology of breast milk jaundice. PMID- 4018101 TI - Calcium homeostasis in the first days of life in relation to feeding. AB - Determinations of serum calcium (Ca), phosphorus (P), magnesium (Mg), calcitonin (CT) and parathyroid hormone (PTH) were carried out in full term newborn infants during the first 168 h of life. The infants were randomly assigned to two different diets: glucose and breast feeding (BF) only or early formula feeding (F). The Ca serum levels decreased from birth to the 24th h; after that time they increased until the 72nd h. The values of serum Ca at the 48th and 72nd h were significantly lower in the F than in the BF group. In contrast, the P serum levels increased from birth to the 48th h and then they decreased; the values of serum P at the 48th h were significantly higher in F than in the BF group. The CT serum levels increased from birth to the 24th h and then they decreased. No difference between the F and BF groups was found during the first 48 h, while at the 72nd h the F group demonstrated significantly higher values of serum CT. PTH serum levels also increased from birth to the 24th h with significantly higher values at the 72nd h in the F group. The results of this investigation demonstrate that the difference in feeding in the first hours of life affects the calcium homeostasis and the secretion of hormones involved in the regulation of serum Ca levels. PMID- 4018102 TI - Lung function in children and adolescents with antecedents of acute rheumatic fever. AB - Static lung volumes, CO-lung transfer, airway resistance, maximal expiratory flows and lung elastic properties were studied in 29 children and adolescents 1 10 years after recovery from acute rheumatic fever. There were essentially no changes in lung function even in the subjects with a residual valvular disease. The only abnormality was a tendency for the elastic lung recoil at TLC to be low, which is interpreted as probably reflecting a decrease in inspiratory muscle force. PMID- 4018103 TI - Disseminated neonatal herpes simplex virus infection acquired from the father. AB - A disseminated herpes virus type 1 infection in a baby was acquired from the father, who had herpes labialis. This was shown by virus strain typing using restriction endonuclease DNA analysis. Labial herpes, a common infection in adults, must be recognised as a potential threat to newborn babies. PMID- 4018104 TI - Severe illness caused by the products of bacterial metabolism in a child with a short gut. AB - An 8-year-old boy with a short gut had six episodes of metabolic acidosis and neurological dysfunction over a 1 month period. The neurological features consisted of a depressed conscious state, confusion, aggressive behaviour, slurred speech and ataxia. The organic acid profile of urine demonstrated increased amounts of lactic, 3-hydroxypropionic, 3-hydroxyisobutyric, 2 hydroxyisocaproic, phenyllactic, 4-hydroxyphenylacetic and 4-hydroxyphenyllactic acids. Of the lactic acid 99% was D-lactic acid. The anaerobic gut flora consisted almost entirely of Lactobacilli in unusually large numbers. A course of vancomycin prevented further episodes. A urinary organic acid profile may be diagnostic when a person with a short gut develops metabolic acidosis or an unusual encephalopathy and bacterial metabolites should be considered in other patients with unusual combinations of organic acids in the urine. PMID- 4018105 TI - Fronto-nasal dysplasia and lipoma of the corpus callosum. AB - A longitudinal study was performed of eight patients with fronto-nasal dysplasia. The follow-up exceeded 15 years in some patients. The eight cases showed lipoma of the corpus callosum. The only clinical alterations observed were cosmetic ones. No neurological abnormality was found, although their intellectual level was just within normal limits, the average IQ being 95, ranging from 82-103. No relationship between the IQ and the type of facies or the size of the lipoma was found. All the children presented psychological alterations, especially misanthropy and shyness. The lipoma was diagnosed by computerised tomography. Two otherwise unidentifiable small lipomas were found with this technique. Pneumoence phalography and carotid arteriography, which had been performed on nearly all the patients before CT scanning, had demonstrated some alterations. These anomalies slightly deformed the anterior portion of the lateral ventricles and anterior cerebral arteries, but a lipoma in the corpus callosum had not been considered. Only in one case was hypogenesis of the corpus callosum clearly demonstrated. The presence of an extra-osseous lipoma on the forehead and of a vertical bony bar in the intracranial midline in contact with the frontal bone are definite signs of the presence of a lipoma in the corpus callosum. The lipoma is in anterior contact with the vertical bony bar. The neurological alterations presented by the patients in this series are minor compared with those described by other authors writing of children with lipoma of the corpus callosum without FND. Because of mild clinical alteration in these children we have not considered removing the lipoma. PMID- 4018106 TI - Cimetidine pharmacokinetics and dosage requirements in children. AB - The pharmacokinetics of cimetidine (10 mg/kg) were investigated in 11 children following an oral dose and in 9 children following an intravenous dose. The children ranged in age from 4-13 years and were undergoing radiology for upper gastrointestinal tract pain. Compared with a group of adults, the children had a higher total body clearance (11.6 +/- 3.4 versus 7.0 +/- 2.5 ml/min per kg; P less than 0.005), a larger apparent volume of distribution (1.24 +/- 0.40 versus 0.80 +/- 0.24 l/kg; P less than 0.005) and a shorter elimination half-life (83 +/ 26 versus 122 +/- 16 min; P less than 0.001) of cimetidine. Renal clearance in children comprised 70% of total body clearance, more than double that of adults (9.0 +/- 1.9 versus 4.2 +/- 2.1 ml/min per kg; P less than 0.001). The area under the cimetidine plasma concentration: time curve after the oral dose was on average 42% in children compared with adults. The mechanism for the increased elimination of cimetidine in children is suggested to be an increase in the renal tubular secretory transport of cimetidine in the kidney. A statistically significant negative correlation was observed between age and cimetidine renal clearance. A cimetidine dosage regimen of approximately 30 mg/kg per day in three to four divided doses would be an appropriate dose in children. PMID- 4018107 TI - Caudal dysplasia and femoral hypoplasia-unusual facies syndrome: different manifestations of the same disorder? AB - The Caudal Dysplasia syndrome and the Femoral Hypoplasia-Unusual Facies syndrome have been reported to be more frequent among infants of diabetic mothers. We report a newborn girl who presented with features compatible with both syndromes. The possibility that both conditions represent different manifestations of the same disorder is discussed. PMID- 4018108 TI - Severe dyspnea and dysphagia resulting from an aberrant cervical thymus. AB - A 5-month-old infant presented with severe dyspnea and dysphagia resulting from a right-sided cervical mass. At 5 months of age, a large aberrant thymus was excised, resulting in the disappearance of all symptoms. Pathological examination showed normal thymus tissue. Since the preoperative chest X-ray film showed a normal thymic shadow and the T-lymphocyte functions were normal, we conclude that this was not an ectopic gland but an undescended thymic implant. PMID- 4018109 TI - Parental age and birth order effects in children with febrile convulsions. AB - This is a study of the parental age and birth order of 100 Chinese children with febrile convulsions compared with 100 controls. The birth order of children with febrile convulsions (1.6 +/- 0.8) was found to be lower than that of the controls (2.1 +/- 1.0), a difference significant at P less than 0.001, whereas there was no significant difference for both paternal and maternal age. Using multiple regression analysis, it was found that the birth order effect was significant at P less than 0.0001. This finding suggests that perinatal factors may play a role in the pathogenesis of febrile convulsions. PMID- 4018110 TI - Errors of morphogenesis and inborn errors of immunity 20 years after the discovery of DiGeorge anomaly. AB - The heuristic concept of "inborn errors of metabolism" was introduced more then 70 years ago and by analogy has prompted the more recent introduction of the term "inborn errors of immunity". It is now well recognized that many inborn errors of immunity can be considered inborn errors of metabolism. Typically, many forms of severe combined immunodeficiency result from adenosine deaminase deficiency, i.e., an inborn error of purine metabolism. On the other hand, errors of immunity are often associated with "errors of morphogenesis", resulting from an intrinsically abnormal developmental process (malformation), a secondary or extrinsic interference with originally normal development (disruption), or an abnormal organization of cells into tissues (dysplasia). Twenty years after the original description, the DiGeorge anomaly should be considered an inborn error of morphogenesis and immunity due either to disruption or less frequently to malformation. In other immunodeficiencies, such as ataxia telangiectasia, the morphologic and immunologic errors result from a dyshistogenesis, i.e., dysplasia. Also, true malformation syndromes, such as Down's syndrome, are consistently associated with immunodeficiency. PMID- 4018112 TI - Prognostic significance of pathological staging in gastrointestinal tumors. PMID- 4018111 TI - Drug-induced toxic epidermal necrolysis (Lyell's syndrome) in a 4-year-old girl. AB - Toxic epidermal necrolysis (Lyell's syndrome) with erythematous skin lesions and bulla formation developed in a 4-year-old girl. An accurate diagnosis using the cryostat technique on the top of a bulla was available within 1 h of hospital admission. The course was unusually mild, probably because of early treatment with corticosteroids. Skin prick tests revealed salicylamide as the agent responsible for inducing the disease. The patient was advised to avoid this substance for the rest of her life. PMID- 4018113 TI - Hormonal steroid receptors in intracranial tumours and their relevance in hormone therapy. AB - Determination of cytosolic estradiol and progesterone receptors was carried out in 30 intracranial tumors: 12 meningiomas, 13 metastases, two angioreticulomas, two gliomas and one sarcoma. The hormonal fraction found with the receptor and the dissociation constant (Kd) were determined by the Scatchard method. Values higher than 10 fmol/mg of protein were considered as positive. Ten of the 12 meningiomas (83%) showed progesterone receptors (RP), while estrogen receptors (RE) were not found in any of the cases; six of the 13 metastases showed the two types of receptors; the other tumors did not present detectable receptor levels. There was no correlation between the receptor level and patient age, sex or hormonal status. Thee results suggest the possible use of endocrine therapy for example in cases of high-risk patients or incomplete surgical resection. PMID- 4018114 TI - Demonstration of hepatic triglyceride lipase-like activity in ascites fluid of mice with sarcoma 180. AB - The contents of apolipoproteins of plasma and ascites fluid of mice with Sarcoma 180 were measured. The apolipoprotein A-I contents of plasma decreased with development of the tumor. The apolipoprotein C-II and C-III contents of plasma reached a maximum on day 7 after tumor inoculation and then decreased. The apolipoprotein A-I content of the ascites fluid was lower than that of normal mouse plasma. In contrast, the apolipoprotein C-II and C-III contents of the ascites fluid were higher than those of normal mouse plasma. The ascites fluid of mice with Sarcoma 180 was found to contain at least two lipases. One had a pH optimum of 5.5-7.0 and was strongly inhibited by chlorpromazine. The other had an alkaline pH optimum and was inhibited only slightly by chlorpromazine. When the ascites fluid was applied to a heparin-Sepharose column 40-45% of the applied triglyceride lipase activity was retained on the column, which was eluted with 0.75 M NaCl. This fraction was inhibited by heat-inactivated (56 degrees C, 10 min) human serum, and was relatively resistant to l M NaCl. These results suggest that one of the lipolytic enzymes present in the ascites fluid of mice with Sarcoma 180 is hepatic triglyceride lipase. PMID- 4018115 TI - Gastrin has no promoting effect on chemically induced colonic tumors in Wistar rats. AB - The effects of prolonged administration of tetragastrin from the beginning of intrarectal instillation of 1 ml of 0.25% N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) and after MNNG-treatment on the incidence and histology of colonic tumors were compared in inbred Wistar rats. In week 35 prolonged administration of testragastrin in depot form from the beginning of MNNG-treatment resulted in a significant reduction in the incidence of colonic tumors and a significant increase in the incidence of mucinous adenocarcinoma, unlike the well differentiated adenocarcinoma produced in controls without gastrin. In contrast, prolonged administration of tetragastrin after MNNG-treatment had little or no influence on the incidence, size or histology of colonic tumors. Thus tetragastrin had no promoting effect on colonic tumors. PMID- 4018116 TI - N-Methylformamide (NSC 3051): a potential candidate for combination chemotherapy. AB - N-Methylformamide (NMF) was found to be non-toxic to the bone marrow as reflected in the absence of leukopenia in mice, even when the marrow had been compromised by prior administration of cyclophosphamide. Thus recovery from the leukopenic nadir after 160 mg/kg of cyclophosphamide was unaffected by 200 mg/kg X 10 of NMF. This combination, given to animals bearing the M5076 sarcoma, proved to have an additive antitumour effect as measured by tumour growth delay and was superior to the antitumour effect of two doses of cyclophosphamide, a regime which prolonged the leukopenia. Furthermore, the hepatotoxicity of NMF was not augmented by the addition of cyclophosphamide. When hepatotoxicity was induced in BALB/c mice bearing the NMF-resistant ADJ/PC6A plasmacytoma, cyclophosphamide fully maintained its antitumour effect. The results show NMF to be a highly specific antiproliferative agent with potential for use in the therapy of patients with a compromised bone marrow and/or in combination chemotherapy. PMID- 4018117 TI - The effect of methotrexate pretreatment on 5-fluorouracil kinetics in sarcoma 180 in vivo. AB - Synergy of sequential MTX and 5-FU has been shown in several in vitro and in vivo systems. In the present study the influence of time interval between MTX and 5-FU and MTX dose on 5-FU accumulation in tumor cells has been examined in Sarcoma 180 in vivo. There was a clear relationship between MTX dose applied and amount of 5 FU detected in the acid-soluble fraction, the RNA fraction and the thymidylate synthase complex fraction. Also, the MTX-5-FU time interval affected clearly the amount of 5-FU detected in all three fractions, the optimum time interval being 8 12 hr. The results indicate that for sequential application of MTX and 5-FU selection of an adequate MTX dose and a sufficient time interval is crucial to achieve synergistic action. PMID- 4018118 TI - Effect of X-irradiation on the pharmacokinetics of methotrexate in rats: alteration of the blood-brain barrier. AB - This study was designed to evaluate the effects of brain irradiation on the permeability of the blood-brain barrier for methotrexate (MTX). Female WAG/Rij rats were cranially irradiated with a single dose of 20 Gy of 300 kV X-rays. At different times (1-15 days) after the exposure the rats were injected intravenously with MTX (25 mg/kg body wt). Irradiation had hardly any effect on the MTX concentrations in the plasma, heart and kidneys as determined by high performance liquid chromatography. However, irradiation resulted in a significant increase of MTX (determined by 125I-radioimmunoassay) in brain tissue per gram wet weight (187.6 +/- 17.9 pmol/g vs 46.4 +/- 29.3 pmol/g in unirradiated brain). This change in permeability of the blood-brain barrier lasted for about 9 days. The MTX elimination from the irradiated brain was the same as that from the non irradiated brain. This indicates that only the MTX uptake and not the elimination by the brain was affected by the irradiation treatment. PMID- 4018119 TI - Distribution of IgM monoclonal antibody in mice with human tumour xenografts: lack of tumour localization. PMID- 4018120 TI - Analgesic effects of cyclazocine and morphine microinjected into the rat dorsomedial hypothalamus demonstrated by the bradykinin-induced flexor reflex test. AB - The analgesic effect of cyclazocine microinjected into the diencephalon of rats was studied by using the bradykinin-induced flexor reflex test. The dorsal portion of the medial hypothalamic area was sensitive to cyclazocine with respect to the production of analgesia (ED50 2.6 micrograms/rat). Microinjections of morphine into the same portion also produced a dose-dependent analgesic effect (ED50 2.5 micrograms/rat). As naloxone (0.9 mg/kg s.c.) antagonized both these analgesic effects, the findings suggest that the dorsal portion of the medial hypothalamic area of the rat is one of the primary target sites of analgesic drugs. PMID- 4018121 TI - Ca-dependent arrhythmogenic effects of maitotoxin, the most potent marine toxin known, on isolated rat cardiac muscle cells. AB - Maitotoxin (MTX) (0.1-10 ng/ml) caused an increase in the degree and the rate of contraction and subsequent arrhythmogenic actions in rat myocardial cells. These effects of MTX were inhibited by verapamil and were abolished by Ca2+-free medium. The MTX-induced effects on cardiac myocytes were enhanced by increasing the Ca2+ concentration. These results suggest that MTX elevates the permeability of cardiac muscle membrane to Ca2+ to increase the intracellular Ca2+ concentration, and thus induces excitatory effects. PMID- 4018122 TI - Further studies on the effects of epimers of thromboxane A2 antagonists on platelets and veins. AB - The C-15 hydroxy epimers of three TXA2/PGH2 antagonists were resolved by HPLC and their pharmacology evaluated in canine saphenous veins and human platelets. For all three compounds, the epimers were equipotent in their ability to antagonize U46619 (1 microM) induced platelet aggregation. In contrast, one of the epimers for all three of the antagonists was significantly more potent than the other in antagonizing U46619 (10 nM) induced saphenous vein contractions. The data support the notion that the TXA2/PGH2 receptors in veins may be different from those in platelets. PMID- 4018123 TI - Angiotensin II enhances calcium exchanges in isolated rat aorta. AB - The effect of angiotensin II (AII) on calcium exchanges in isolated rat aorta was investigated using the 45Ca lanthanum technique. AII induced a rapid (10 s) and long-lasting (120 min) increase of calcium uptake and enhanced calcium release for a short period. AII-stimulated calcium uptake was antagonized by saralasin and verapamil but not by indomethacin. These data indicate that AII increases rat aortic calcium exchanges via receptor-operated and voltage-dependent calcium channels. PMID- 4018124 TI - Inhibition of protein carboxylmethylation and dopamine autoreceptor functioning. AB - S-Adenosyl-L-homocysteine (SAH, 2-100 microM) greatly inhibited protein carboxymethylation (PCM) in rat striatal synaptosomes, but did not alter the ability of apomorphine and other DA agonists to inhibit DA synthesis. SAH (10 microM) also did not significantly alter the ability of either 0.5 or 1.0 microM apomorphine to inhibit DA release from superfused rat striatal tissue slices, but it did antagonize the response to 5.0 microM apomorphine. The former two concentrations of apomorphine predominantly affected only DA release, whereas the latter concentration suppressed both DA and acetylcholine release. These findings are discussed with regard to the possible relationship between DA autoreceptor functioning and PCM activity. PMID- 4018125 TI - Some in vitro receptor binding properties of [3H]eticlopride, a novel substituted benzamide, selective for dopamine-D2 receptors in the rat brain. AB - The substituted benzamide compound eticlopride, (S)-(-)-5-chloro-3-ethyl-N-[(1 ethyl-2-pyrrolidinyl) methyl]-6-methoxysalicylamide hydrochloride (FLB 131), has been shown to selectively block dopamine-D2 binding sites in the rat brain. The compound was tritium-labelled to high specific radioactivity and was used for in vitro receptor binding studies. [3H]Eticlopride was found to bind specifically to rat brain homogenates with the highest binding in the striatum and lowest in the hippocampus. The binding was saturable with a high number of binding sites (49.5 pmol/g) and with very high affinity (0.17 nM). As with other benzamides, the binding of [3H]eticlopride was highly sodium-dependent. Lesioning of the striatal neurons with ibotenic acid reduced the binding by 50% while lesioning of the nigrostriatal pathways with 6-hydroxydopamine was without effect on the observed binding. The binding of [3H]eticlopride was inhibited potently by neuroleptic drugs, while compounds known not to interact with the dopamine-D2 binding sites were inactive. It is concluded that this new dopamine-D2 antagonist may be a useful tool for the study of dopamine-D2 binding sites due to its high affinity and good selectivity. PMID- 4018126 TI - Antinociceptive effects of orphenadrine citrate in mice. AB - The antinociceptive effect of orphenadrine citrate, a muscle relaxant, was investigated in mice. Four different pain tests were selected to involve different noxious stimuli. Clear antinociceptive effects were found in the formalin test. The increasing temperature hot-plate test showed a biphasic dose response relationship with slight hyperalgesia after low doses and hypoalgesia after higher doses. No significant effects of orphenadrine (0-25 mg/kg) were found in the tail flick and constant temperature hot-plate tests. The data suggest that orphenadrine may reduce, enhance or leave unaffected different types of nociceptive transmission. Orphenadrine may also possess analgesic properties in conditions not involving muscle spasm. PMID- 4018127 TI - Effects of pincainide on contractile responses and 45Ca movements in rat isolated vascular smooth muscle. AB - The effects of pincainide, a new beta-amino anilide, on contractile responses and 45Ca fluxes were studied in rat aorta and on spontaneous mechanical activity in rat portal veins. Pincainide (10(-5) to 10(-2) M) produced a dose-dependent inhibition of noradrenaline (NA) and high K+ -induced contractions. These inhibitory effects were observed with pincainide added either before or after the induced contractions. The Ca2+ -induced contractions of K+ -depolarized aorta as well as the spontaneous mechanical activity of portal veins were also inhibited by pincainide. Pincainide (5 X 10(-3) M) inhibited the 45Ca influx stimulated by 10(-6) M NA and increased 45Ca efflux. It was concluded that in isolated rat aorta, pincainide not only inhibited the influx of Ca2+ reducing the contractile responses to NA and high K+ but it also inhibited other effects related to NA induced release of intracellular Ca2+ stores. PMID- 4018128 TI - Binding characteristics of the bungarotoxin fraction II-S1 to rat brain membranes. AB - Bungarotoxin fraction II-S1 (designated BGT II-S1), isolated from the venom of Bungarus multicinctus, appears to affect nicotinic transmission in rat sympathetic ganglia through its phospholipase activity. On the other hand, the present investigation suggests that other modes of interaction of this toxin with nervous tissue may also exist as, in a rat brain membrane preparation, binding of this toxin to a specific binding site can be demonstrated. In a buffer containing calcium, binding of [125I]BGT II-S1 saturated with a Bmax of approximately 16 fmol/mg protein and a Kd of 5 nM. This site did not appear to be directly linked to the nicotinic acetylcholine recognition site as the binding was not displaced by nicotinic agents; however, alpha-bungarotoxin, which interacts with a nicotinic-like site in neural tissue, did affect the binding and, conversely, BGT II-S1 inhibited the binding of [125I]alpha-bungarotoxin. PMID- 4018129 TI - Histamine-mediated acetylcholine release in the guinea-pig ileum. AB - The isometric contraction induced by histamine in guinea-pig ileum longitudinal muscle was biphasic in Krebs ([Ca]: 3.36 mM) but monophasic in Tyrode solution ([Ca]: 1.80 mM). The late phase (histamine: 20-400 nM) was common to the two solutions but the early phase (histamine: 2-20 nM) was observed only in Krebs solution. This early phase could be blocked with atropine (0.01-0.2 microM), morphine (0.1, 1 microM), adenosine (5, 20 microM) and tetrodotoxin (0.3 microM) without affecting the late phase. Washout of morphine or adenosine was fast. Neostigmine (100 nM) greatly potentiated the effect of histamine (4 nM) in the early phase, the muscle undergoing almost maximum contraction but also reversible desensitization to doses of histamine less than or equal to 20 nM for as long as 40 min after washout. Beyond this concentration, the preparation responded to increasing doses of histamine as observed in the late phase. It is concluded that low concentrations of histamine that have no observable direct effect on muscle contractility release acetylcholine in the presence of [Ca] 3.36 mM, the early phase being entirely due to release of endogenous acetylcholine. PMID- 4018130 TI - Effect of some anti-inflammatory drugs on FMLP-induced chemotaxis and random migration of rat polymorphonuclear leucocytes. AB - The effect of indomethacin, acetyl salicylic acid and niflumic acid on the chemotaxis and random migration of rat polymorphonuclear leucocytes (PMN) was investigated with a modified Boyden chamber technique under various experimental conditions (two cell sources, administration of drugs in vivo or incubation in vitro, modulation of antichemotactic activity of sera obtained from animals with inflammatory reactions). Indomethacin and niflumic acid inhibited the chemotactic responsiveness of cells collected from the rat pleural cavity after induction of two types of acute inflammatory reactions. This action was dose-dependent and appeared after either in vivo administration of the drug or in vitro incubation of the cells with various concentrations of the drug. However, random migration was not significantly modified and acetyl salicylic acid had no effect under any of the conditions. The same drugs, acetyl salicylic excepted, inhibited the antichemotactic activity exhibited by sera obtained from animals with inflammatory reactions. PMID- 4018131 TI - Novel opioid peptides derived from mitochondrial cytochrome b: cytochrophins. PMID- 4018133 TI - Separation of tolerance to the behavioral effects of LSD from changes in serotonin receptor binding in cats. AB - Nearly complete tolerance to a test dose of 50 micrograms/kg of LSD occurred within 24 h following an initial dose of 50 micrograms/kg of the drug, using limb flicking and abortive grooming as as behavioral indices in the cat. No changes in serotonin receptor binding were observed at this time. However, chronic administration of LSD (50 micrograms/kg every 12 h for 6 days) produced a significant decrease in serotonin receptor binding in both the forebrain and brainstem plus spinal cord. These data suggest that the behavioral effects of LSD and tolerance to LSD as measured here are mediated predominantly by different sites. PMID- 4018132 TI - Pharmacological analysis of 5-hydroxytryptamine actions on guinea-pig ileal mucosa. AB - The possibility that 5-hydroxytryptamine (5-HT) is involved in the chloride secretory response evoked by electrical stimulation of submucosal neurons was investigated in guinea-pig ileum set up in Ussing flux chambers. When electrical stimulus pulses of 0.5 ms duration, amplitude of 3.2 mA and frequency of 10 Hz were applied repetitively in the plane of the tissue, a biphasic increase in short-circuit current (Isc) occurred. After tachyphylaxis to 5-HT or when the 5 HT antagonist cisapride was present in the bathing solutions, electrical stimulation of enteric nerves still evoked a biphasic change in Isc that was similar in magnitude to the response before either treatment. Cisapride (5 microM) prevented the mucosal response to exogenous 5-HT without altering the functional integrity of the tissues. Addition of 100 microM 5-HT to the submucosal side of the tissue evoked a biphasic increase in Isc that reflected primarily chloride secretion. Tetrodotoxin and atropine significantly reduced but did not abolish the change in Isc and chloride secretion. These results suggest that the mucosal response evoked by electrical field stimulation is not mediated by release of 5-HT at neuro-enterocyte junctions or from endocrine elements. 5 Hydroxytryptamine activated enteric cholinergic neurons within the submucosal plexus to stimulate chloride secretion. PMID- 4018134 TI - Effect of local GABA administration on rat ovarian blood flow, and on progesterone and estradiol secretion. AB - The effect of gamma-aminobutyric acid (GABA)--superfused onto the surface of the ovary--on ovarian blood flow and on estradiol-17-beta (E2) and progesterone (P) secretion was studied in anaesthesized, pseudopregnant rats. GABA, 0.5 mumol per 50 microliter per animal, significantly reduced the blood pressure in the femoral artery, increased ovarian blood flow, enhanced the rate of E2 release and markedly decreased P secretion. The present findings indicate that local GABAergic mechanisms may be involved in the regulation of ovarian blood flow and hormone secretion. PMID- 4018135 TI - Insurmountable antagonism of ouabain-induced coronary constriction by prazosin. AB - A linear dose-response curve was produced by the addition of ouabain (10(-8)-10( 6) M) to the media bathing segments of porcine right coronary arteries. A concentration of 10(-6) M ouabain produced constriction equal to 47% of that resulting from exposure to 35 mM KCl. The ouabain dose-response curve was competitively displaced one order of magnitude by the previous addition of verapamil (2.2 X 10(-8) M), and non-competitively by the prior exposure to prazosin (6.5 X 10(-7)-6.5 X 10(-13) M). The inhibitory effect of prazosin appears to be unrelated to its alpha 1-adrenergic blocking action. PMID- 4018136 TI - Prolactin analgesia: tolerance and cross-tolerance with morphine. AB - The development of acute tolerance to prolactin-induced analgesia in mice was identified by using the writhing test. This tolerance was antagonised by naltrexone pretreatment indicating a role of an opioid mechanism. Cross-tolerance between morphine and prolactin was observed with regard to analgesia. These data show that prolactin mimics morphine properties as far as analgesia is concerned and serve as evidence supporting prolactin-opioid interaction. PMID- 4018137 TI - The role of dopamine in the formation of gastric ulcers in rats. AB - A single dose of the dopamine agonists L-dopa, bromocriptine or apomorphine produced a protective effect by significantly shortening of the length of stomach ulcerations. A single dose of the dopamine antagonists haloperidol, sulpiride or domperidone potentiated the ulcerogenic effect by extending the length of stomach ulcerations. These results point to the fact that dopamine is involved in the rise and development of experimental stomach ulcers. PMID- 4018138 TI - Electrophysiological actions of flecainide in normal and infarcted canine Purkinje fibers. AB - The electrophysiological effects of flecainide, 0.1, 0.5 and 1.0 mg/l, on action potential characteristics were examined in normal Purkinje fibers and Purkinje fibers surviving infarction, at stimulation cycle lengths of 1000 and 300 ms. Overshoot, amplitude and dV/dtmax were reduced significantly in a dose-dependent manner by flecainide in both normal Purkinje fibers and Purkinje fibers surviving infarction. Action potential duration was shortened by flecainide to a greater extent: at the cycle length of 1000 ms compared to 300 ms; at 50% repolarization compared to 90%; and in normal preparations compared to infarcted preparations. Activation time was increased by flecainide in a dose-dependent manner in both types of preparations. This effect was enhanced at the shorter cycle length. In both normal and infarcted preparations, flecainide shortened the ERP of those having a longer initial ERP and lengthened those with a shorter ERP. This effect was significant only at the stimulation cycle length of 1000 ms. This study indicates that flecainide has properties unique and different from traditional antiarrhythmic drugs. PMID- 4018139 TI - Kinetic and pharmacological profiles of the in vitro binding of the potent dopamine agonist [3H]N,N-dipropyl-5,6-dihydroxy-2-aminotetralin to rat striatal membranes. AB - The in vitro binding of the new tritiated dopaminergic ligand [3H]N,N-dipropyl 5,6-dihydroxy-2-aminotetralin to rat striatal membranes is described. Binding assays were performed in 50 mM Tris-HCl pH 7.5 containing 1 mM EDTA and 0.01% ascorbic acid at 25 degrees C for 30 min. Specific binding at 0.5 nM [3H]DP-5,6 ADTN and 5 mg/ml membrane suspension was very high (87-93%) and was found to be linearly related with homogenate concentration over the range of 0.5-10 mg/ml (r = 0.9968). (+)Butaclamol 1 microM was used to define specific binding. Specific binding disappeared completely within 20 min when the tissue was incubated at 55 degrees C. Association and dissociation curves (obtained after addition of 1 microM (-)-DP-5,6-ADTN) were converted to linear logarithmic plots and the kinetic constants were computed (k1 = 0.054 min-1 and k-1 = 0.0188 min-1) as were the t1/2 for association (3.52 min) and dissociation (20.8 min). This resulted in an apparent KD of 0.34 nM. Increasing concentrations of [3H]DP-5,6-ADTN (0.05-3.0 nM) were found to saturate the receptor site. Linear transformation of the saturation curves and presentation of the curves as Eadie-Hofstee plots showed that only one set of receptors was labeled (nHill was 0.995 +/- 0.07) with a high affinity constant KD of 0.57 +/- 0.10 nM and a maximum number of binding sites Bmax of 18.6 +/- 2.4 pmol/g tissue. Various compounds were tested for their potency to displace the specific binding of [3H]DP-5,6-ADTN to striatal membranes (2.5 mg/ml).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4018140 TI - The effects of lidoflazine and flunarizine on cerebral reactive hyperemia. AB - Cerebral blood flow in the rat was monitored by a venous outflow technique with an extracorporeal circulation, which allows for the continuous recording of flow over periods of several hours. The bi-fluorophenyl-piperazine derivatives, lidoflazine and flunarizine, enhanced the reactive hyperemia elicited by a brief (30 s) anoxic challenge. They did not alter resting cerebral blood flow rates. Verapamil, a potent calcium slow channel blocker, decreased resting flow rates but did not alter the duration of the reactive hyperemia. As lidoflazine and flunarizine are potent inhibitors of adenosine uptake, whereas verapamil is not, the results are consistent with the hypothesis that adenosine plays a significant role in cerebral vascular autoregulation. PMID- 4018141 TI - Pregnancy: increased effect of verapamil in human uterine arteries. AB - The effect of verapamil on the contractile response to norepinephrine in isolated, suffused uterine arteries from pregnant and nonpregnant humans was investigated. The arteries, obtained after hysterectomy, were dissected free from surrounding tissue and arterial rings were prepared and mounted in tissue chambers filled with Krebs-bicarbonate solution. Isometric tension was recorded. There was no significant difference between arteries from pregnant patients and arteries from nonpregnant patients when maximal contractile response and sensitivity to norepinephrine were compared. At concentrations of 0.3 and 3 microM, verapamil attenuated the response to norepinephrine in uterine arteries from both pregnant and nonpregnant patients. However, verapamil was significantly more potent in blocking the response to norepinephrine in arteries from pregnant patients. PMID- 4018142 TI - The antagonism of acetylcholine excitatory and inhibitory responses of Helix central neurones, by some neuromuscular blocking drugs. AB - Intracellular recordings were made from identified central neurones of the snail Helix aspersa. The antagonism of acetylcholine excitatory and inhibitory responses by d-tubocurarine, HS818 and HS626 was investigated. d-Tubocurarine was equipotent against both the inhibitory and excitatory responses, while HS626 and HS818 were of similar potency to d-tubocurarine in antagonising acetylcholine excitation but were approximately one order of magnitude less potent in antagonising the inhibitory response. PMID- 4018143 TI - Use-dependent effects of amiodarone on Vmax in cardiac Purkinje and ventricular muscle fibers. AB - Superfusion with 5 micrograms/ml amiodarone for 3-4 h induced use-dependent Vmax block in dog Purkinje and guinea pig ventricular muscle fibers. The recovery from block was exponential with tau of 289 +/- 30 ms in Purkinje (n = 7) and 282 +/- 47 ms in muscle (n = 6) fibers. The onset of frequency-dependent Vmax block was rapid, i.e. reached steady state after 4.2 +/- 0.5 beats (n = 5). The combination of rapid interaction with sodium channel and the reported action potential lengthening make amiodarone unique among Class I antiarrhythmic drugs. PMID- 4018144 TI - Influences of gender and maturation on responses of guinea-pig airway tissues to LTD4. AB - LTD4 was more potent in airway tissues from immature male and female guinea-pigs than in those from mature animals. The intrinsic activity of LTD4 relative to carbachol was greatest in tracheal tissues from immature animals. Indomethacin treatment reduced the potency of LTD4 and increased maximal contractile responses in most tissues. The reduced potency of LTD4 as a consequence of maturation may be significant for the decrease in airway reactivity seen in children at adolescence. PMID- 4018145 TI - The effect of isoprenaline on the ciliary activity of an in vitro preparation of rat trachea. AB - A dose dependent increase in the ciliary beat frequency of rat tracheal explants was found over a 10(-7)-10(-3) M concentration range of (+/-)-isoprenaline and was abolished by 10(-7) M propranolol. Furthermore (+)-isoprenaline, a drug which is much less potent in its action on beta-adrenoceptors than its (-)-isomer, failed to cause a stimulation. We conclude that the acceleration in the intrinsic ciliary beat frequency by (-)-isoprenaline, although occurring at a relatively high concentration compared with the action of the drug on other tissues, is mediated by beta-adrenoceptors. PMID- 4018146 TI - Clinical and pathogenic studies on aged polyuria in the IVCS strain of mouse. AB - As aged polyuria is often observed in the IVCS strain of mouse, biochemical and histological studies were undertaken in order to clarify its etiology. Polyuria was observed at 7-8 months of age, and significant increases in water intake and urine volume were noted at 10-11 months of age. IVCS strain mice over one year old showed water intakes and urine volumes about five to six times greater than those in DDI strain mice. The osmolarity of urine excreted from polyuric mice was low compared with DDI strain mice, and elevations of sodium and potassium excretion were observed at an early stage of polyuria. At a more advanced stage of the disease, proteins of low molecular weight were excreted in most animals. Furthermore, depression of kidney response to ADH was recognized soon after onset of polyuria compared with normal IVCS strain mice. Thus, polyuria observed in IVCS strain mice may result from a functional defect of the renal tubules. In addition, significant deposition of amorphous substances, especially in the liver, kidney and spleen, occurred almost in parallel with polyuria. From these findings, it is obvious that mice of the IVCS strain exhibit characteristic polyuria and storage disease as they age. PMID- 4018147 TI - [Abnormal findings in the ocular fundi of colony-born cynomolgus monkeys]. AB - The ocular fundi of 1,151 apparently healthy colony-born cynomolgus monkeys (Macaca fascicularis) ranging in age from newborn to 19 years were examined using an ophthalmoscope. Two hundred and thirty-eight abnormal findings were recorded in 219 of the 1,151 monkeys. Of these, 23 were related to the optic disc and 115 to the retinal vessels. Of the remaining 100 abnormal findings, 91 were retinal degenerations and 9 were retinal hemorrhages. The 23 optic disc abnormalities consisted of 3 cases of micropapilla, 4 of ectasia and 16 of myelination of the retinal nerve fibers. Of the 115 retinal vascular abnormalities, 87 were arterial tortuosity, one was venous tortuosity, 2 were tortuosity of both artery and vein, 2 were artery-vein crossing, 20 were copper-wire artery, one was inosculation of the artery, one was vascularization of the vein and one was persistent hyaloid artery. Of the 91 retinal degenerations, one was degeneration of the periphery of the macular and the optic disc, 8 were macular degeneration and 82 were peripheral degeneration. Nine cases of retinal hemorrhages appeared under 6 years of age. PMID- 4018148 TI - [An outbreak of staphylococcal dermatitis in laboratory mice]. AB - An epizootic of dermatitis with erosion, ulcer and crust broke out in an experimental colony of JCL-ICR mouse over a period from December 1975 to June 1976. The disease was detected in 592 of a total of 1831 mice of 3-24 months old, especially in males of 7-24 months old (517/821). At the beginning of December 1975, only a few males of 12 months old were found to have the lesion on the back skin, and thereafter the dermatitis prevailed gradually among the mice. Histopathologic examinations showed the loss of the epidermis, necrosis and/or collapse of the corium, accumulation of serous exudate with neutrophilic cell infiltration and a few cocci scattered on the surface. In chronic cases, fibrous granulation tissues with neutrophilic cell infiltration were formed in the corium. Staphylococcus aureus was isolated in pure culture from the skin lesions in all of the mice examined. Skin disease similar to that of the field case was reproduced in mice inoculated subcutaneously with 10(7) viable organisms of the fresh isolate. By giving chlortetracycline in drinking water for 7 days, treatment of the affected mice was efficacious in mild cases, but not in severe cases. PMID- 4018149 TI - [Measurement of serum prolactin and the effect of ketamine anesthesia on serum prolactin levels in cynomolgus monkeys (Macaca fascicularis)]. AB - The effect of an anesthetic, ketamine, on the serum prolactin level was examined in wild-originating female cynomolgus monkeys (Macaca fascicularis) imported from South East Asia. Serum prolactin levels were measured by the homologous radioimmunoassay system which was developed for human prolactin. The validity was confirmed by using an extract of pituitary gland from a female cynomolgus monkey as well as serum and amniotic fluid from a pregnant monkey. Additionally, serum luteinizing hormone (LH) levels were determined by the radioreceptor assay system developed in our laboratory using Leydig cells collected from rat's testes as a receptor fraction. The experiment was repeated three times at one-month interval, using twenty animals that were divided into three groups consisting of 5, 7 and 8 monkeys each. In the first experiment, the first group was injected with physiological saline and the second and third groups were intramuscularly given ketamine at a dose level of 5 mg/kg B.W. and 15 mg/kg B.W., respectively. In the second experiment, the first and second groups were given ketamine at a dose of 5 mg/kg B.W. and of 15 mg/kg B.W., respectively, and the third group was served as control injected with saline. In the third experiment, the first and third groups were administered with 15 mg/kg and 5 mg/kg of ketamine and the second group was injected with saline. In short, all of the twenty monkeys received the three different treatments for two months. The serum prolactin level showed a marked increase after the administration of ketamine.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4018150 TI - [A method for developing hereditary deficiency of complement component in the rabbit]. AB - A two-way selective experiment for total hemolytic complement activity (CH50) was carried out in a colony of New Zealand White rabbits for the purpose of developing hereditary deficiency of complement component and estimating the realized heritability (h2) of CH50. The results obtained were as follows. 1) The mean value of CH50 with a standard error (SE) in 203 adults rabbits was 9.0 +/- 0.2 U/ml, and the range of CH50 was 2 to 18 U/ml. 2) Individual differences of CH50 in rabbits were comparatively stable regardless of time and season. 3) The realized heritability (h2) of CH50 was estimated to approximately 0.3. 4) Two rabbits with a hereditary C8 alpha-gamma deficiency were obtained from a cross between low CH50 individuals (male: 5.9 U/ml X female: 5.6 U/ml). From other crosses (male: 3.2 U/ml X female: 5.6, 5.7 U/ml), five rabbits with a hereditary C6 deficiency were obtained. 5) The frequencies of C8 alpha-gamma and C6 deficient genes in the colony were estimated to at least 0.005, 0.003, respectively. 6) It was suggested that a downward selection for CH50 was a useful method for developing hereditary deficiency of complement component in the rabbit. PMID- 4018151 TI - Rats with congenital tremor and curled whiskers and hair. AB - In a colony of Kyo: Wistar strain of rats, we found animals with curled whiskers and hair. These rats exhibited tremor when they moved. There were no sex differences in phenotype and behavior, and the affected animals of both sexes were sterile. Among pairs that produced at least one tremulous offspring, 21.8% of the females and 21.7% of the males were affected; these proportions suggest that the anomaly is caused by an autosomal recessive gene. When the presumed heterozygous males were crossed with WAG/Rij females, about half of their female F1 hybrids were heterozygous, and they produced 26.1% (43/165) of the affected offspring when backcrossed to the sires. Again these results suggested that the disorder is caused by an autosomal recessive gene. We tentatively designated the gene as tremor (tm). The main pathological changes were seen in the gonad and central nervous system. The gonads of both sexes were aplastic even in adult animals. Vacuole formation was seen widely in the central nervous system and sometimes exhibited a spongy appearance. After administration of alpha-methyl-p tyrosine, the norepinephrine content of the cerebellum was high, indicating that some anomalies of catecholamine release were present. The mutation is being maintained by random mating of the littermates of affected animals. Detailed pathological, endocrinological, neuropharmacological, and genetical studies are proceeding. PMID- 4018152 TI - [Morphological study on the hypoplastic testis with aplasia of the epididymis, ductus deferens, and gland of the ductus deferens in the TW inbred rat]. AB - In the TW inbred rat, about 50% of the males show bilateral or unilateral testicular hypoplasia with aplasia of the ipsilateral epididymis, ductus deferens and gland of the ductus deferens. To investigate the pathogenesis of the testicular abnormality in the TW rats, the weight and morphology of the testes on the aplastic and normal side were studied between one week and one year of age. The weight of the testes on the affected side was greater than those on the normal side at four and five weeks. However, it rose to a plateau at six weeks and then remained at about one half to one third the weight of a normal testis. As for the testicular histology, there were no obvious changes from one day to three weeks of age. The diameter of the seminiferous tubules became larger and the number of germ cells decreased at four and five weeks. At six weeks, degeneration and loss of germ cells were observed and many multinucleated giant cells appeared. Thereafter, the loss of germ cells became more severe, and they eventually disappeared with increasing age, but Sertoli's cells continued to exist. In the interstitial area, edematous changes and proliferation of Leydig's cells were observed. The efferent duct of another strain, with normal testes, was ligated at three weeks of age, and changes of the testis after the operation were examined to investigate whether or not these anomalies of the TW strain were due to the absence of the accessories, which may block the excretion of the testicular fluid.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4018153 TI - [Occurrence of sick animals in conventional guinea pigs obtained from commercial breeders during 1964 to 1982]. AB - A quarantine was performed on conventional Hartley guinea pigs free from Streptococcus zooepidemicus, Bordetella bronchiseptica and Salmonella spp., but infected with Eimeria caviae, which were purchased from twenty-five commercial breeders by the National Institute of Health. Physical examinations revealed an incidence of 0.88 per cent or 1,461 sick animals in 166, 050 guinea pigs quarantined during the period 1964 to 1982. The result obtained showed the following significant differences between the periods 1964 to 1971 and 1972 to 1982: Annual incidence of sick animals in the period 1972 to 1982 increased twice as many as 0.56 to 0.81 per cent during the 1964 to 1971, and monthly incidence showed bimodal occurrence at April and October in the former period but continual occurrence from November to April in the latter period. Major clinical signs in the former period were death and diarrhea, which occurred usually within a week after arrival of the guinea pigs at our institute and caused significant decrease of body weight, but those in the latter period were retarded growth and weakness which became detectable during 1-3 weeks after arrival of the animals. Discussions were made on possible reasons concerning the differences in incidence of sick animals during the two periods. PMID- 4018154 TI - [Three successful cases of artificial insemination in chimpanzees]. AB - Artificial inseminations were performed on two female chimpanzees from July 1981 to April 1983 and three conceptions were obtained. Semen samples collected by rectal probe method of electroejaculation were incubated at 37 degrees C for about 20 minutes for liquefaction. Liquefied portion of the semen was sucked up into polyethylene tube about 30 cm in length attached to a syringe and was inseminated into cervix of each female of which pelvic region was raised in prone position under anesthesia. Ovulation time was speculated by swelling of sex skin in earlier two cases and by urinary LH level in last case. Three offsprings were obtained 234, 235 and 235 days after last insemination, respectively. All of three show normal developments. PMID- 4018155 TI - Spontaneous teratoma in a Sprague-Dawley rat. AB - An 6-week-old male Sprague-Dawley rat which had undergone no experimental treatment died from enlargement of the abdomen. At necropsy, a spherical mass measuring about 3 X 4cm in diameter was connected to the retroperitoneal region cross to the middorsal line of the body. The tumor was composed of skin, ganglion, striated and smooth muscle, cartilage, bone, pancreas, glands, lymph node, and fibrous and adipose tissue, and diagnosed as teratoma. PMID- 4018157 TI - [Symposium: Advances in research on infectious diseases of laboratory animals]. PMID- 4018156 TI - [Net protein utilization of stock diets for rats and mice]. AB - Male Sprague-Dawley rats of six weeks of age were fed on ten percent crude protein diets for a ten day experimental period. The net protein utilization (NPU) by carcass analysis of six kinds of revised stock diets for rats and mice was compared with that of purified whole-egg protein and milk casein. NPU values for all revised stock diets and milk casein were lower than those for purified whole-egg protein. Compared to milk casein, two kinds of revised stock diets showed lower NPU, but the remaining four diets had similar NPU. PMID- 4018159 TI - Distribution of 125I-thyroxine in different organs and tissues of dietically obese rats. AB - The distribution of 125I-thyroxine (% dose/g tissue; tissue/plasma radioactivity ratio) was investigated in different tissues of 28-week-old obese Wistar rats. Obesity was induced by high-fat diet (HFD) and confirmed by carcass analysis; in heavy obese animals the relative and absolute fat content is increased twofold and threefold, respectively, compared to control rats fed on a low-fat diet (LFD). Heavy HFD rats exhibit diminished 125I-T4 distribution in the "slow pool" (fat tissue, muscle) and unchanged values in the "fast pool" (liver, kidney) in comparison with LFD rats with low body weight. The differences in distribution presented here are not caused by the diet per se, but they are the consequence of the obesity of the animal, because no differences in the 125I-T4 distribution were found in the 125I-T4 between HFD and LFD rats with relatively equal body weight and body composition. The reduced T4 distribution in the fat tissue of obese rats is discussed in connection with possibly decreased lipolysis in this tissue and possible causal participation in the beginning of obesity. PMID- 4018158 TI - Prevention by vitamin A of the occurrence of permanent vaginal and uterine changes in ovariectomized adult mice treated neonatally with diethylstibestrol and its nullification in the presence of ovaries. AB - Permanent proliferation and cornification of the vaginal epithelium occurred in adult ovariectomized (OVX) mice which had received neonatal injections of 5 micrograms diethylstilbestrol (DES). Occurrence of the permanent epithelial proliferation was prevented by injections of 200 IU vitamin A acetate (VA) given simultaneously with neonatal DES-treatment in mice when OVX at 30 days of age, but not in those OVX at 270 days. For the suppression of the permanent vaginal changes, however, more than one month were required after DES plus VA-treatment. In DES plus VA-treated OVX (at 30 days) mice, the vaginal epithelium indicated a lower mitotic rate than in DES-treated OVX mice. Clear cells were found in the degenerating vaginal epithelium in 63% of DES plus VA-treated OVX mice, while in the proliferated epithelium, this type of cells appeared only in 10% of DES treated OVX mice. In 40% of 180-day-old, DES-treated OVX (at 30 days) mice, permanent stratification took place in the uterine epithelium, while it was inhibited in the age-matched DES plus VA-treated OVX mice. However, the uterine change was not prevented in 310-day-old, DES plus VA-treated mice when OVX at 270 days. This findings suggests that the relatively long-term presence of ovaries nullifys the inhibitory effect by VA on the occurrence of permanent changes in the utero-vaginal epithelium induced by neonatal DES treatment. PMID- 4018160 TI - Simple diagnosis of diabetes insipidus and antidiuretic hormone excess. AB - The value of information that may be obtained by measuring osmolality of body fluids is not generally appreciated by clinicians. Osmolality determination by freezing point depression is technically simple to perform and requires only 0.2 ml fluid. The simultaneous measurement of plasma and urine osmolality may yield useful information concerning alterations in water homeostasis (diabetes insipidus and antidiuretic hormone excess) and avoid uncomfortable and sometimes hazardous investigations of patients. PMID- 4018161 TI - Inhibitory effect of 17-beta-estradiol on the activity of liver alanine aminotransferase in adult female rats. AB - The inhibitory effect of daily s.c. administration of cca 50 micrograms kg-1 17 beta-estradiol on liver alanine aminotransferase activity of adult female rats, the absence of this effect after bilateral adrenalectomy and its reappearance after gluccorticoid substitution is described. PMID- 4018162 TI - Plasma oxytocin concentrations in man after different routes of administration of synthetic oxytocin. AB - Plasma oxytocin was determined by RIA in three male subjects under basal conditions and following administration of synthetic oxytocin. As compared to basal levels (below 10 pg/ml), plasma oxytocin was found to be elevated markedly (36 to 85 pg/ml) in response to application by nasal spray (total dose: 65 to 100 micrograms). Intramuscular injection (25 micrograms) resulted in very high oxytocin levels (360 to 480 pg/ml), whereas buccal administration (70 micrograms) was proved to be ineffective (levels below 10 pg/ml plasma). In each case, plasma vasopressin remained unchanged. PMID- 4018163 TI - Effect of beta-casomorphin and its analogue on serum prolactin in the rat. AB - The effects of exogenous opioid peptides beta-casomorphin Tyr-Pro-Phe-Pro-Gly-Pro Ile and its analogue Tyr-Pro-Gly-Pro-Phe-Pro-Ile (analogue I) were found to increase prolactin level in plasma after intraperitoneal injection. Analogue I was more potent. This effect of beta-casomorphin and analogue I were blocked by an opioid antagonist, naloxone. These results indicate that the exogenous opioid peptides (exorphins) may participate in the regulation of prolactin secretion. The similarity of analogue I with enkephalin structure was discussed. PMID- 4018164 TI - Detoxification of hydrogen peroxide by the rabbit iris-ciliary body. AB - When the intact rabbit iris-ciliary body was incubated in Tyrode's solution containing 10(-4) M hydrogen peroxide, the concentration of hydrogen peroxide remaining in solution diminished rapidly. The iris-ciliary body was homogenized and centrifuged at 100 000 g. It was observed that the hydrogen peroxide detoxification activity was resident primarily in the 100 000 g supernatant and not in the pellet. The hydrogen peroxide detoxification activity was found to be inactivated by heat and to be non-dialyzable. Gel filtration chromatography experiments revealed that breakdown of hydrogen peroxide by the ciliary body was not a 'bulk effect' due to generalized oxidation of tissue constituents. In fact, the active principle, localized by gel filtration chromatography, identified closely with catalase. These observations indicate that catalase within the iris ciliary body enables the tissue to detoxify hydrogen peroxide from solution. Catalase might protect the iris-ciliary body from damage by hydrogen peroxide generated by normal physiological or pathophysiological conditions. PMID- 4018165 TI - Calcium-induced lens protein aggregation accelerated by reactive oxygen species photosensitized in the presence of hydroxykynurenines. AB - Photo-oxidation with 3-OH L-kynurenine O-beta-glucoside or 3-OH L-kynurenine accelerates the aggregation of water-soluble protein in the rat lens due to the presence of calcium ion. The present report demonstrates that hydrogen peroxide and superoxide anion mediate a large part of the photodynamic acceleration with hydroxykynurenine compounds. In addition, 3-OH L-kynurenine O-beta-glucoside seems to photosensitize more of the two reactive oxygen species than 3-OH L kynurenine. The findings are discussed together with other photodynamic effects of hydroxykynurenine compounds. PMID- 4018166 TI - Tyrosine-to-tryptophan energy transfer and the structure of calf gamma-II crystallin. AB - The efficiency of electronic energy transfer from tyrosine to tryptophan residues in the lens protein calf gamma II crystallin has been determined from measurements of fluorescence excitation spectra at 25 degrees C and independently from phosphorescence spectroscopy at 77 K. The total transfer efficiency from the fifteen tyrosines to the four tryptophans in native calf gamma II was found to be t = 78 +/- 10%, at 25 degrees C. The expected value based on Forster theory and the X-ray structure of the protein is t = 83%, in good agreement with the present experimental result. The transfer efficiency measured in denatured calf gamma II at 25 degrees C was t = 20 +/- 10%, in good agreement with the value t = 25% expected for the completely denatured protein, based on Forster theory and the known amino acid sequence. These results are of interest for several reasons. First, energy transfer can provide a simple , experimental confirmation of lens protein structures determined from X-ray data or from computer modeling studies. Second, the present studies show that energy transfer measurements can be used to monitor the effect of denaturants on lens protein structure, an aspect not readily investigated by X-ray crystallography. Third, the present electronic energy transfer studies may be relevant to understanding the mechanism of UV photodamage in lens proteins and hence in whole lenses. PMID- 4018167 TI - Detoxification of H2O2 by cultured rabbit lens epithelial cells: participation of the glutathione redox cycle. AB - Although it has been shown that cultured rabbit lenses can adequately defend against the 0.03-0.05 mM level of H2O2 normally found in aqueous humor, the contribution of the epithelium in this process has not been well defined. In the present study, the peroxide-detoxifying ability of the epithelium is evaluated in cultured rabbit lens cells established from 4-6-day-old rabbits and compared to that of skin fibroblasts from rabbits of the same age. When cells were cultured in medium containing H2O2, the concentration of peroxide rapidly decreased; however, various concentrations could be maintained for 3-hr periods by using glucose oxidase to enzymically generate H2O2. At an extracellular level of 0.03 mM H2O2, the rate of detoxification of peroxide by epithelial cells was 2 mumol H2O2 (8 x 10(5) cells)-1 3 hr-1, twice as fast as that for fibroblasts. Epithelial cells contained a high level of reduced glutathione (GSH) equal to 36 nmol (8 x 10(5) cells)-1, twice that present in the fibroblasts. The concentration of GSH in 8 x 10(5) epithelial cells, a number of cells normally present in one intact rabbit lens epithelium, remained constant during 3 hr of exposure to H2O2 levels as high as 0.03 mM, even though the amount of H2O2 taken up under these conditions was sufficient to oxidize completely the cellular GSH every 2 min. In contrast, the GSH content of fibroblasts declined at levels of peroxide above 0.01 mM. Participation of the glutathione redox cycle in the H2O2 detoxification process was demonstrated from studies of hexose monophosphate shunt (HMPS) activity as measured by oxidation of [1-14C]-labeled glucose. The oxidation of [1-14C]-glucose in epithelial cells was stimulated 13 times that of controls during exposure to 0.04-0.05 mM H2O2, while the corresponding increase in oxidation of [6-14C]-labeled glucose was only 1.6 times. In contrast, maximum shunt activity in fibroblasts occurred at 0.03-0.04 mM H2O2 and was six times the control value. The growth potential of the cells following a 3-hr exposure to H2O2 was also used as a measure of oxidant toxicity in both cell types. Concentrations of H2O2 up to 0.03 mM had no effect on the growth of 8 x 10(5) epithelial cells but did diminish the growth of the same number of fibroblasts. Cell density was found to be an important parameter in the ability of the cells to tolerate H2O2.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 4018168 TI - Glucocorticoid-lens protein adducts in experimentally induced steroid cataracts. AB - The injection of glucocorticoids into the vitreous chamber of the rabbit eye results in the development of posterior subcapsular opacities. These lesions appear to be similar in morphology to human steroid-induced cataracts. Electron microscopic analysis revealed fiber cell separation, vacuolization, and changes within the matrix of the crystallins. Opacification could only be produced by glucocorticoids possessing a reactive C-20,21 hydroxylcarbonyl function, supporting the hypothesis that glucocorticoid addition products are involved in the induction of these lesions. The occurrence of glucocorticoid-lens proteins adducts was confirmed by tritium incorporation and by radioimmunoassay of protein hydrolysates obtained from these lenses. PMID- 4018169 TI - Hereditary retinal degeneration in the Rhode Island Red chicken: ultrastructural analysis. AB - An electron microscopic analysis of photoreceptor degeneration in a congenitally blind strain of chickens is presented. The mutation was named rd, meaning 'retinal degeneration'. Although the chicks were behaviorally and electrophysiologically blind at the time of hatching, their retinas appeared morphologically comparable to normal chicks at this stage. Both groups had well developed photoreceptor cells, although outer segments were typically disoriented or misaligned. In the normal, and to some degree in the rd, retina, outer segments became organized within the first week posthatching. In the rd retina at that time, however, more outer segments were disorganized and disoriented. Disc like membranes were also seen in some inner segments. Many photoreceptors had distended inner segment tips containing a granular cytoplasm. Membraneous debris was present in the subretinal space. Over the next 2-3 weeks there was a reduction in number of inner segments, outer segments and photoreceptor nuclei of both rods and cones. Photoreceptor cell bodies in the outer nuclear layer were replaced by Mueller cell processes. By the end of the second month, a larger cone:rod ratio was apparent, and a large proportion of the remaining cones were double cones. Intact outer segments were rarely seen at that time. Few and sporadic cone cells, identified by a pale-staining oil droplet, were the predominant surviving photoreceptors by 6 months of age. At the later stages examined, the pigment epithelium (PE) appeared to be undergoing degenerative changes. A general thinning of cells and hypopigmentation of PE cells was apparent, although hyperpigmented, hypertrophied PE cells were also present which bulged into the subretinal space. Pigmented cells of unknown origin were also noted in the subretinal space at the later time points. PMID- 4018170 TI - Minified diagnostic contact lenses for biomicroscopic examination and photocoagulation of the anterior and posterior segment in small primates. PMID- 4018172 TI - Gerontism: a neologism. PMID- 4018171 TI - Age-related differences in food intake, body weight, and survival of male F344 rats in 5 degrees C cold. AB - Male F344 rats, 3, 12 and 21 months old, were acclimated at 5 degrees C for 7 to 9 weeks. Controls were maintained at 23 degrees C. Food intakes and body weights were monitored weekly. All animals in these age groups survived. However, 25 month-old rats placed in 5 degrees C for 3 weeks had only a 46% survival. All age groups responded to 5 degrees C exposure by different but always significant increases in food intake. Peak food intake was 100% above basal in the 3- and 21 month-olds and 80% above the basal in the 12-month-olds. These increases were sufficient to maintain body weights in the 3- and 12-month-olds, but in the 3 month-olds growth was retarded. The 100% increase of food intake in the 21-month olds was not adequate to maintain body weight. The 25-month-old rats also increased their food intake significantly in cold, but large weight loss incurred in both the survivors and the non-survivors. Food intake and energy efficiency were different at different ages and under different environmental conditions in male F344 rats. PMID- 4018173 TI - Aging of membrane transport mechanisms in the central nervous system--high affinity choline transport in rat cortical synaptosomes. AB - High affinity choline transport has been studied in cortical synaptosomes from rats ranging from 2 months to 30 months of age. Initial velocities were measured as a function of both choline and sodium concentration. These data give similar fits to a kinetic model which was previously found to give minimal best fit to data from 2-month-old animals. Thus, aging has apparently not altered the fundamental mechanism by which carrier, sodium, and choline interact in the process of uptake. Although some small differences in initial velocities were found between data from young and older animals, these differences showed no pattern and were not statistically significant. It is concluded that the choline transporter is unaffected by age, in contrast to the transporters for GABA and glutamic acid, whose transport capacities were found to decline with age. PMID- 4018174 TI - Evidence of Schwann cell degeneration in the aging mouse motor end-plate region. AB - An ultrastructural evaluation was made of the changes encountered in the motor endplates of the gastrocnemius muscle of old mice in comparison with young-adult mice. In old, 27-month-old mice, a great variety of changes were recorded. The main abnormalities occurred in the axon terminals, the myoneural junctional folds, and the endomysial space. Loss of synaptic vesicles and mitochondria and vacuolization of axon terminals were common. Shrinkage and degenerative changes of axon terminals were noticed. The end-plate abnormalities were closely associated with an increased amount of collagen tissue, degenerated Schwann cells, and cell debris. Degenerated Schwann cells were not encountered in young adult mice. In the old group, endplates of normal appearance occurred in the proportion of 40%. The young group had normally structured end-plates in the proportion of 85%. The lesions described are not specific for the aging process. PMID- 4018175 TI - Age changes in density of endometrial stromal cells of the rat. AB - Stromal cells were counted in the endometrium of the rat during aging. Cell counts were made in the subepithelial, middle and deep regions of the endometrium in the left uterine horn of virgin Sprague-Dawley rats at 36 days of age and at 4, 10, and 20-24 months. In all regions of the endometrium the density of stromal cells decreased with aging. Decrease in cell numbers per unit area was greatest in the middle and deep endometrium. In 20 to 24-month-old rats, the mean number of cell profiles within 0.085 mm2 of the middle endometrium had decreased to less than one-third the number that was present within the same area in the 36-day animal. In the deep endometrium of these oldest rats, the mean number of cells had decreased to less than one-fourth. An age-associated decrease in density of stromal cells may contribute to alterations that have been observed in hormone dependent uterine synthetic activities during aging. PMID- 4018176 TI - Inefficiency of chest percussion in the physical therapy of chronic bronchitis. AB - The effect of manual chest percussion was studied in 10 patients recovering from an acute exacerbation of chronic bronchitis. All patients were studied on 2 consecutive days. Physiotherapy consisting of postural drainage and instructed coughing was given on both days. Chest percussion was included in a randomized way on either day. Percussion was associated with a small but statistically significant increase in airflow obstruction, measured as a reduction in FEV1 after the treatment. There were no differences in the deposition or clearance of inhaled radiolabelled particles between the 2 forms of treatment. Changes in oxygen saturation were small and insignificant during both forms of treatment. The study indicates that manual chest percussion is of little value as an adjunct to postural drainage and instructed coughing in the treatment of patients with chronic bronchitis. PMID- 4018177 TI - Irritative complaints, carboxyhemoglobin increase and minor ventilatory function changes due to exposure to chain-saw exhaust. AB - Complaints of irritation in the eyes, nose and throat as well as dyspnea during work prompted this study to determine whether chain-saw exhaust produces acute exposure effects in loggers. Interviews concerning respiratory symptoms and rating of complaints were conducted for 211 loggers at industrial health care centers. Measurements of carboxyhemoglobin, spirometry and exposure to hydrocarbons, carbon monoxide and aldehydes were assessed for 23 loggers over 36 work periods lasting 2 h each. The prevalence of chronic bronchitis among the 211 loggers was 6%. Irritative complaints of eyes, nose and throat were common and significantly higher than in a reference group. The exposure levels were all below established threshold limit levels, except for carbon monoxide. There was a significant correlation between carbon monoxide exposure and blood carboxyhemoglobin levels. A small but significant decrease of FEV1% and FEF 25 75% during the work periods indicated minimal broncho-constriction, possibly mediated through a reflex mechanism due to irritation of upper airways. PMID- 4018178 TI - Association between rise in antibodies and increase in airway sensitivity after intramuscular injection of killed influenza virus in asthmatic patients. AB - Nineteen stable asthmatic patients were given killed influenza virus intramuscularly. In 9 patients who developed a fourfold or greater rise in haemagglutination antibodies, an increase in airway sensitivity to histamine was demonstrated 48 h later. There was no significant change in histamine sensitivity in those patients who failed to develop a fourfold rise in haemagglutination antibodies. The increased histamine sensitivity was not associated with a deterioration in asthma symptoms, peak expiratory flow, nor an increase in bronchodilator requirements. PMID- 4018180 TI - The effect of furoyl saccharin, a novel non-peptidic acylating protease inhibitor, on experimental emphysema in the hamster. AB - Furoyl saccharin was evaluated for its ability to prevent the development of emphysematous lesions produced in hamsters by the exposure to aerosolized papain (3% for 3 h). Pretreatment with intratracheal furoyl saccharin (at the doses of 0.3, 1, 3 mg) reduced the appearance of papain-induced emphysema as evaluated by both physiologic (static compliance) and histologic (mean linear intercept and internal surface area of the lungs) methods. Inhibition was dose-related with maximal reduction of changes in static compliance (74%), mean linear intercept (84%) and internal surface area (65%) observed after a dose of 3 mg. This is the first time that a non-peptide acylating inhibitor of serine proteases is reported to be affective in preventing the development of experimental emphysema. PMID- 4018179 TI - Effect of long-term administration of digoxin on exercise performance in chronic airflow obstruction. AB - We have studied the effect of long-term digoxin on exercise performance in 15 patients with pulmonary heart disease due to severe chronic airflow obstruction (FEV1/VC ratio 29 +/- 6%: mean +/- SD). Digoxin (0.25 mg/day) was given for 8 weeks in a randomized, double-blind crossover, placebo-controlled trial. All patients were ambulatory and had clinical features of right ventricular dysfunction but no clinical evidence of left ventricular dysfunction. Assessments included progressive and steady-state exercise, pulmonary function studies and evaluation of right and left ventricular function. In all patients the right ventricular ejection fraction was reduced; in 4 patients the left ventricular ejection fraction was also reduced. In patients whose left ventricular ejection fraction was initially abnormal, 8 weeks of digoxin increased left ventricular ejection fraction to normal. In spite of the improvement in resting ventricular function, exercise performance, the cardiopulmonary response to exercise, pulmonary function and general health status did not improve. We conclude that in patients with pulmonary heart disease: 1) digoxin improves ventricular function only if left ventricular function is reduced, and 2) despite the improvement in ventricular function digoxin does not improve pulmonary function, cardiopulmonary response to exercise or general feeling of well being. PMID- 4018181 TI - Hemoptysis in sarcoidosis. AB - We describe 4 previously healthy patients with non-cavitated pulmonary sarcoidosis, whose presenting symptom was hemoptysis. Despite the presence of pulmonary involvement in about 90% of patients with sarcoidosis, hemoptysis as the presenting symptom is very rare and was described previously, to our knowledge, in only 5 patients. PMID- 4018182 TI - Generalized amyloidosis in cystic fibrosis. AB - A boy suffering from cystic fibrosis (CF) complicated by generalized amyloidosis is reported. His condition was fairly good during the first 10 years of life, but after this time he had repeated pulmonary infections caused by Staphylococcus aureus. From the age of 14, he developed increasing hepato- and splenomegaly and a liver biopsy revealed massive amyloidosis. At the age of 16 he died of respiratory and cardiac failure. Post-mortem examination revealed wide-spread amyloidosis in addition to pulmonary and pancreatic findings characteristic of CF. PMID- 4018183 TI - Flow cytometric DNA analysis. PMID- 4018184 TI - Characterization of pleural effusions by flow-cytometric DNA analysis. AB - Pleural effusions from 58 patients were studied by cytology and flow-cytometry. Relative cellular DNA content was measured, giving an estimate of ploidy as well as cell cycle distribution. Twenty-one patients had non-malignant diseases while the rest had malignant diseases. Pleural effusions from 13 patients contained malignant cells. In 2 cytologically equivocal cases and in one cytologically negative case aneuploid cells were demonstrated in the histograms. The cell cycle distribution of the diploid tumour cells did not differ from that of the diploid cells in benign effusions. The demonstration of an aneuploid histogram by flow cytometry favours a cancer diagnosis, and can provide valuable and decisive information in addition to cytological results. PMID- 4018185 TI - Bronchial reactivity to histamine in young male smokers. AB - Bronchial reactivity to inhaled histamine was determined in 17 non-asthmatic young male smokers and 21 non-smokers who were free of airflow obstruction. The 2 groups were similar in forced expiratory volume, maximal expiratory flow at 50% and 25% of vital capacity, slope of phase III of the single-breath nitrogen test (delta N2/l) and closing volume (CV/VC%). Bronchial reactivity was determined as PC20, provocation concentration reducing FEV1 by 20%, threshold concentration reducing FEV1 by two standard deviations, percentage reduction in FEV1 with histamine 16 mg/ml. Similar numbers of smokers and non-smokers had a PC20 below 16, 32 and 64 mg/ml. Threshold concentrations were the same in smokers and non smokers, as was the reduction in FEV1 with histamine 16 mg/ml. The bronchoconstrictor response to histamine was significantly related to baseline measurements of expiratory flow (particularly in non-smokers), but not to delta N2/l or CV/VC%. Bronchial reactivity to histamine is not increased in young male smokers with normal lung function. The abnormal reactivity seen in older smokers is acquired, either from prolonged exposure to cigarette smoke itself, or resultant airway narrowing. PMID- 4018186 TI - Ventricular fibrillation in myocardial sarcoidosis. AB - A 35 year old male with intractable ventricular fibrillation due to myocardial sarcoidosis is described. Myocardial involvement in patients with sarcoidosis is not uncommon. Since severe ventricular arrhythmias due to myocardial sarcoidosis are often refractory to conventional antiarrhythmic treatment, steroids should be tried. PMID- 4018187 TI - Familial idiopathic fibrosing alveolitis. AB - Case reports of two sisters with idiopathic fibrosing alveolitis are presented. On the basis of reports in the literature it seems that developmental anomalies and immunopathological changes occur more frequently in familial fibrosing alveolitis than in the general population. PMID- 4018188 TI - Bronchoesophageal fistula caused by pulmonary aspergillosis. AB - A 29-year-old patient developed a bronchoesophageal fistula after expectorating a mycetoma caused by Aspergillus fumigatus. After failure of medical therapy, a retrosternal coloplasty was performed. Pulmonary aspergillosis can be the cause of a bronchoesophageal fistula. PMID- 4018189 TI - Topographical distribution of the summation property of Y-ganglion cells in the cat retina. AB - The stimulus response characteristics (SRCs) of 33 phasic retinal ganglion cells were established on the basis of extracellular recordings in the optic tract of anaesthetized and paralyzed cats. All SRCs were best described with two straight lines in double logarithmic coordinates. The near threshold light intensity summation was found to be linear, on the average up to 4.8 times threshold. The cells' threshold, defined as smallest response outside the 95%-confidence interval of the spontaneous activity (SpA) distribution, is dependent on the slope of the gain near threshold (linear gain) and the standard deviation of the spontaneous activity (SpA-scatter) prior to stimulation. The slope of the double logarithmic relationship at higher intensities (non-linear gain) - corresponding to the exponent of the power function - increases with threshold intensity. The linear, near threshold gain was used to describe the retinotopic distribution of the cells' threshold- and suprathreshold sensitivity. This sensitivity is high in the center of the retina decreasing steadily towards the periphery. Threshold, as well as linear and non-linear gain are interdependent parts of the SRC, specific for each ganglion cell and, furthermore, the geometrical mean between threshold activity and the response activity at the intersection point of the two regression lines is constant around 30 imp/s, irrespective of the cell's range of operation. The entire course of the SRC can therefore be predicted on the basis of the SpA-scatter and threshold intensity. The homogeneous population of investigated Y-ganglion cells proved to be a set of cells with summation characteristics, changing systematically with threshold and the distance of the receptive field from area centralis. PMID- 4018190 TI - Cerebello-cortical linkage in the monkey as revealed by transcellular labeling with the lectin wheat germ agglutinin conjugated to the marker horseradish peroxidase. AB - The possibility of a cerebellar linkage, via the thalamus with medial area 6 of the cerebral cortex was further explored in the present experiments (cf. preceding companion paper). It was found that HRP conjugated to the lectin wheat germ agglutinin injected into motor cortical areas was transported beyond the thalamus to the contralateral intracerebellar nuclei when the survival time was 4 7 days. It is suggested that the labeling in the deep cerebellar nuclei occurred via the thalamic relay where cerebellofugal fibre terminals had taken up the marker substance released by corticothalamic fibre terminals or by the retrogradely labeled thalamic perikarya. In general, transcellular labeling of perikarya was weaker than retrograde labeling in the thalamic cells. Some of the nuclear zones in the cerebellum showed relatively dense granulations of the reaction product; in other zones only cells with few granules were seen, and large parts of the nuclei were not labeled at all. The topography of secondary labeling in the cerebellar nuclei depended on the cortical injection sites. In all cases, most labeling was found in the contralateral dentate nucleus. The interposed nucleus received a fair amount of heavy labeling only in the precentral arm and face cases. Very little labeling was seen in the fastigial nucleus and in the cerebellar nuclei ipsilateral to the cortical injections. A somatotopic organization of secondary labeling was noted in the precentral cases with the face being represented caudally, the hindlimb rostrally and the arm between the face and the hindlimb representation. This is in agreement with previous anatomical and electrophysiological investigations. These observations thus lend support to the conclusion that the SMA receives a transthalamic input not only from the basal ganglia but also from the cerebellum, especially from its lateral, neo-cerebellar portion. PMID- 4018191 TI - The laryngeal sensory pathway and its role in phonation. A brain lesioning study in the squirrel monkey. AB - In 10 squirrel monkeys (Saimiri sciureus) uni- or bilateral lesions were placed in the nucl. solitarius, parabrachial nuclei, nucl. ventralis posterior medialis thalami or face area of primary sensory cortex. The effects of these lesions on vocalization were compared with those after transection of the internal branch of the superior laryngeal nerve. It was found that neither the cortical nor thalamic or parabrachial lesions changed the acoustic structure of vocalization. In contrast, destruction of the nucl. solitarius, like transection of the internal branch of the superior laryngeal nerve, affected vocalization severely. It is concluded that the production of species-specific vocalization depends upon a di- or, possibly, tri-synaptic laryngeal reflex control from tactile and proprioceptive laryngeal mechanoreceptors via nucl. solitarius and, possibly, lateral medullary reticular formation to nucl. ambiguus. PMID- 4018192 TI - Effects of posterior parietal lesions on visually guided movements in monkeys. AB - Four monkeys were trained to position, with either hand, a vertical rod in front of one of 5 target lights spaced 20 degrees apart on a semicircular screen. After the monkeys had reached the preoperative criterion (80% trials correct per session) they received a 1- or 2-stage bilateral lesion of posterior parietal cortex restricted to area 7. The lesion produced in all the monkeys considerable but temporary changes in movement latency, accuracy, velocity and duration. Latency increase appeared to be independent of changes in the other parameters. After the first lesion, movement latency increased for the contralateral arm in both left and right working spaces, from 100 ms up to 400 ms depending on the animal. A second lesion symmetrical to the first one increased movement latency of the arm contralateral or ipsilateral to the last lesion, depending on the time interval between the two lesions. In addition, unilateral lesions of area 7 induced a gross inaccuracy in movements of the arm contralateral to the lesion, more marked in the contralateral working space. These lesions also increased movement peak velocity and simultaneously decreased movement duration for the arm contralateral to the lesion. The increase in velocity appeared to be related to the decrease in duration. A second lesion of area 7 in the opposite hemisphere similarly affected accuracy, velocity and duration but for the arm contralateral to the second lesion. PMID- 4018193 TI - Projections from the nuclei prepositus hypoglossi and intercalatus to the superior colliculus in the cat: an anatomical study using WGA-HRP. AB - In view of the recognized role of the superior colliculus (SC) in eye and head movement, and following recent physiological studies, the presence of afferents to the SC from the vestibular complex and adjacent cellular groups were sought using axonal transport techniques. Injections of wheat germ agglutinin conjugated to horseradish peroxidase (WGA-HRP) were made in the SC of 9 adult cats. Retrogradely labelled cells were observed in the nuclei prepositus hypoglossi (PH) and intercalatus (INT) predominantly contralaterally with only occasional cells in the medial (MVN) and descending (DVN) vestibular nuclei contralaterally. There appeared to be some topographical differences in anteroposterior distribution of labelled cells in the perihypoglossal nuclei after restricted SC injections. Two cases of intramedullary injection of WGA-HRP which involved the PH, INT, MVN and DVN revealed anterogradely labelled terminations in laminae IV and VI of the contralateral SC. A few additional labelled terminations were found in the medial portion of the contralateral medial geniculate body (MGB) and the nucleus of the optic tract-(NOT). The possible role of the perihypoglossal nuclear complex as a site of convergence of vestibular and neck afferent inputs destined for the SC is discussed. PMID- 4018194 TI - Organization of projections from the principal sensory trigeminal nucleus to the hypoglossal nucleus in the rat: an experimental light and electron microscopic study with axonal tracer techniques. AB - The organization of projections from the principal sensory trigeminal nucleus (PSN) to the hypoglossal nucleus (XII) in the rat was investigated at the light and electron microscopic level with retrograde and anterograde axonal tracer techniques. Microiontophoretic injection of horseradish peroxidase (HRP) into XII resulted in retrograde labeling of neurons confined to the dorsal one-third of the PSN. Labeled neurons were found bilaterally, although a clear preponderance for ipsilateral distribution was evident. Most labeled neurons were found in the medial one-third and caudal two-thirds of the PSN. Labeled neurons were large (30 50 micron), round-to-pear shaped multipolar cells with dendrites oriented primarily in the mediolateral direction. At the electron microscopic level, HRP reaction product was found throughout the cytoplasm of soma and processes of PSN projection neurons. The ultrastructural characteristics of these cells included a round, centrally placed nucleus and invaginated nuclear envelope, sparse Nissl bodies, numerous free ribosomes, mitochondria, lysosomes and Golgi complexes. Three to four main stem dendrites gradually tapered from the cell body and numerous synaptic terminals impinged upon soma and dendrites of labeled PSN neurons. Microiontophoretic injection of tritiated amino acids or HRP into the dorsal one-third of the PSN resulted in moderately dense terminal labeling in XII bilaterally, although mainly ipsilaterally. Terminal labeling was found diffusely throughout all regions of XII. Fibers descended the brainstem in the dorsolateral reticular formation and entered XII ventrolaterally. At the electron microscopic level, boutons containing HRP reaction product were found to synapse on dendritic processes in XII. Labeled boutons were characterized by clear, spherical vesicles and an asymmetrical postsynaptic density. The significance of these results are discussed in relation to oro-lingual motor behavior. PMID- 4018195 TI - Interhemispheric influences on area 19 of the cat. AB - Anatomical studies have shown an extensive network of homotopic and heterotopic interhemispheric connections in area 19 of the cat visual cortex (Segraves and Rosenquist 1982a; 1982b). We have investigated their functional organization by recording visual responses in area 19 of cats following a midsagittal section of the optic chiasm. This operation interrupts all crossed optic fibers coming both from the nasal and the temporal retinae; as a result, each hemisphere receives optic fibers only from the lateral hemiretina of the ipsilateral eye which conveys information from the contralateral visual field. Visual information transmitted to the same hemisphere from the contralateral retina and the ipsilateral visual field must be attributed to an indirect, interhemispheric pathway. We found that a rather high proportion of neurons (31.8%) in area 19 of seven split-chiasm cats responded to visual stimuli presented to the contralateral eye. All neurons receiving this interhemispheric activation were also driven by the ipsilateral eye via an intrahemispheric pathway. The property of binocularity was significantly related to the visuotopic map in that both receptive fields of each binocular neuron adjoined or were in the immediate vicinity of the vertical meridian. Due to the small size of receptive fields in area 19, the contribution of the interhemispheric pathway to the representation of the visual field is rather limited and it is certainly less extensive than that predicted by anatomical studies. The representation of the ipsilateral visual field in area 19 of intact cats, as assessed electrophysiologically, was comparable to that found in split-chiasm cats. Recordings in areas 17-18 of split chiasm cats showed that the visual field represented through the corpus callosum in these visual areas is certainly not less and probably more, extensive than that found in area 19. The results support the conclusion that the relation to the vertical meridian and the receptive field size can explain the organization of the interhemispheric connections in the visual areas studied so far. PMID- 4018196 TI - Human ocular counterroll: assessment of static and dynamic properties from electromagnetic scleral coil recordings. AB - Static and dynamic components of ocular counterroll as well as cyclorotatory optokinetic nystagmus were measured with a scleral search coil technique. Static counterroll compensated for about 10% of head roll when the head was tilted to steady positions up to 20 deg from the upright position. The dynamic component of counterroll, which occurs only while the head is moving, is much larger. It consists of smooth compensatory cyclorotation opposite to the head rotation, interrupted frequently by saccades moving in the same direction as the head. During voluntary sinusoidal head roll, cyclorotation compensated from 40% to more than 70% of the head motion. In the range 0.16 to 1.33 Hz, gain increased with frequency and with the amount of visual information. The lowest values were found in darkness. The gain increased in the presence of a visual fixation point and a further rise was induced by a structured visual pattern. Resetting saccades were made more frequently in the dark than in the light. These saccades were somewhat slower than typical horizontal saccades. Cyclorotatory optokinetic nystagmus could be induced by a patterned disk rotating around the visual axis. It was highly variable even within a same subject and had in general a very low gain (mean value about 0.03 for stimulus velocities up to 30 deg/s). It is concluded that cyclorotational slip velocity on the retina is considerably reduced by counterroll during roll of the head, although the residual cyclorotation after the head has reached a steady position is very small. PMID- 4018198 TI - Evidence for spatial structure in the cortical input to the monkey lateral geniculate nucleus. AB - We combined visual stimulation of the corticogeniculate pathway with cryogenic blockade of area 17 to examine the visual spatial structure of the cortical influence on single macaque LGN cells. Excitatory central areas surrounded by inhibitory regions and vice versa were found with equal frequency. Unstructured influences were also seen. The structure of the influence suggests that modulation of the spatial parameter may be an important function for the corticogeniculate pathway. PMID- 4018197 TI - The auditory corticopontocerebellar projection in the rat: inputs to the paraflocculus and midvermis. An anatomical and physiological study. AB - This study investigated afferent projections to the cerebellum, in particular those from the auditory cerebral cortex. The parafloccular lobule of the rat cerebellum is shown to be a primary target for the auditory cortical information with the midvermal region being a receiving area from the inferior colliculus. The method of anterograde transport of tritiated amino acids was employed to determine projections of the auditory cortex to the pons. Autoradiography showed that the site of termination of efferents from the auditory cortex corresponds to the location of neurons that project to the paraflocculus. Histogram analysis of neuronal activity in halothane anesthetized rats was employed to determine the response characteristics of neurons in paraflocculus and midvermis following cortical and tectal electrical stimulation. In addition, unit recordings of parafloccular neurons in immobilized, locally anesthetized animals demonstrated general characteristics of the responses of these neurons to auditory field stimulation. Electrical stimulation of the auditory cortex evoked mixed, excitatory-inhibitory and pure inhibitory mossy fiber responses in 33% of neurons in the paraflocculus, with no responses evident in the midvermis. Following inferior collicular stimulation, 12.6% of the neurons in the midvermis elicited a response. Recordings from parafloccular neurons in unanesthetized, immobilized rats showed evidence for excitatory and inhibitory mossy fiber responses, following auditory field stimulation. This spectrum of basic studies establishes the existence of a pathway in which the paraflocculus is revealed as an integrating target for cortical auditory information. PMID- 4018199 TI - Sex-specific effects of estradiol on hypothalamic noradrenaline turnover in gonadectomized rats. AB - In long-term gonadectomized rats of either sex a single injection of estradiol-17 beta 3-benzoate acutely decreased the turnover rates of noradrenaline in the preoptic-anterior hypothalamic brain area (POAH) and reduced the serum concentrations of luteinizing hormone (LH). On the afternoon of day 3, between 72 and 78 h after estrogen priming, an increase of noradrenaline turnover was observed in female rats, whereas the turnover remained low in males. The increase of noradrenergic activity in female rat brain occurred at the time when LH release could be stimulated by progesterone. On the other hand, the low noradrenergic activity in the POAH of male rats correlated with the lack of stimulatory progesterone effects on LH secretion. The data indicate that estradiol induces a sex-specific increase of noradrenaline turnover in the POAH. This increase appears to be a prerequisite for the induction of LH surges. PMID- 4018200 TI - Luminance detectors in the olivary pretectal nucleus and their relationship to the pupillary light reflex in the rat. II. Studies using sinusoidal light. AB - The luminance detectors in the olivary pretectal nucleus, which are likely candidates mediating the pupillary light reflex, responded to all frequencies of sinusoidally modulated light up to 12-25 Hz. At low frequencies (0.05-4.0 Hz) the luminance detectors responded with modulated firing to different stimulation rates. The modulation depth of the cell response increased with the increase in stimulation frequency up to 20 Hz, then rapidly fell. There was a delay between the peak intensity of the stimulus and the peak firing of cell response of about 30-40 ms. The amplitudes of the consensual pupil responses to the same sinusoidal stimulus, on the other hand, decreased with an increase in frequency and no discernible response was recorded above 2 Hz. The pupil responses were little affected by sympathectomy. The differences in the frequency response characteristics of luminance detectors and the pupil were attributed to the sluggish dynamic properties of the pupil muscles. This was demonstrated using an electronic model of the iris muscle which modified the responses of the luminance detectors giving output waveforms broadly resembling pupil responses to square and sinusoidally modulated lights. PMID- 4018201 TI - The thalamic connections with medial area 6 (supplementary motor cortex) in the monkey (macaca fascicularis). AB - The interrelationship of medial area 6 (supplementary motor area) with the thalamus was investigated by means of anterograde and retrograde tracing methods. Nine monkeys were prepared for autoradiography or histochemistry with the marker HRP conjugated to the lectin wheat germ agglutinin. Three of the monkeys received injections into the precentral cortex for comparison. Previous observations were confirmed that the thalamic relays to the motor areas are organized as crescent shaped lamellae which transgress cytoarchitectonic boundaries. The thalamic VA-VL complex receiving fibres from areas 4 and medial area 6 also sends fibres to these same areas. The thalamic relay to medial area 6 comprised the following subdivisions: VLo, VLc, area X of Olszewski, VLm and, to a smaller extent VA. Labeling (mostly anterograde only) was also prominent in some thalamic compartments outside the 'motor' thalamus: R, CL, CM-Pf, MD, LP, PULo. It was noted that rostral and caudal injections into the medial area 6 resulted in different thalamic labeling: The rostral portion was found to be related mainly with VApc, area X and VLc, the central portion with VLo, and the caudal portion with VLc/VLo. This structural inhomogeneity may reflect also a functional rostro caudal differentiation of the medial area 6. The thalamic territory projecting to the precentral cortex is separate from the above relay and includes principally VPLo. The present anatomical labeling study is in agreement with the conclusion of Schell and Strick (1984) that the SMA, especially its central portion, is an important target of basal ganglia outflow via the thalamic relay VLo. In addition consistent labeling was also found in thalamic subdivisions (area X, VLc) which had been found to receive cerebellar fibres. PMID- 4018202 TI - Mapping of regions in the caudal brain stem that produce stimulus-bound synchronization in the cortical EEG. AB - This study was aimed at filling the lacunae in our knowledge regarding the localization of the regions in the caudal brain stem that bring about cortical EEG synchronization on electrical stimulation and characteristic features of synchronized waves elicited from those regions. Studies were conducted on 40 encephale isole cats. Stimulation of ventromedial regions of the caudal brain stem, with low frequency, elicited stimulus-bound synchronized waves in the cortex which were more prominent ispsilaterally. On the other hand, low-frequency stimulation of dorsal and lateral areas produced synchronized waves which were either equally prominent on both sides, or more prominent on the contralateral side. The loci in the brain stem that produce synchronization were very specific. The induced synchronized waves showed amplitude modulation and did not outlast the train of stimuli. The results are further confirmation of the role of caudal brain stem structures in cortical EEG synchronization. They also provide information regarding the nature of cortical synchronization elicited from these brain stem structures. PMID- 4018203 TI - Alterations in preoptic unit activity on stimulation of caudal brain stem EEG synchronizing structures. AB - Effects of stimulation of EEG-synchronizing structures of the caudal brain stem reticular formation with low (6 Hz) and high (100 Hz) frequencies were studied on 42 neurons of the preoptic area, in encephale isole cats. Though low-frequency stimulation produced excitation and inhibition, the majority of the influenced neurons of the preoptic area had effects of the former type. Cortical EEG synchronization was also induced by low-frequency stimulation of the caudal brain stem. High-frequency stimulation, on the other hand, produced inhibition in a majority of the influenced neurons and induced, mostly, desynchronization of the cortical EEG. A majority of the neurons that were inhibited on high-frequency stimulation, remained unaffected during low-frequency stimulation. The influence induced on the preoptic area neurons by low-frequency stimulation could be obtained even in the absence of cortical EEG synchronization. Changes induced on preoptic neurons by high-frequency stimulation may be partially related to induced cortical EEG desynchronization. PMID- 4018204 TI - Depression and recovery of metabolic activity in rat visual system after eye removal. AB - To examine the anterograde metabolic effects of visual system damage, unilateral eye enucleation was carried out in 19 black-hooded rats, and the animals were injected with 2-deoxy[14C]glucose at postoperative survival times ranging from 1 h to 91 days. Metabolic depression followed by recovery to near-normal resting levels of activity was seen contralateral to the enucleation in the superior colliculus and the dorsal and ventral lateral geniculate nucleus (primary effects), and in the lateral posterior nucleus, in layer IV, and the infragranular layers of visual cortex (secondary effects). Diaschisis, defined as a temporary depression in neural activity after denervation, appears to be a characteristic response of the damaged visual system. PMID- 4018205 TI - Transplantation of fetal rat cortex into regenerating nerve to the biceps femoris of adult rat. AB - Morphological aspects of the implantation of 11-day-old fetal (E11) rat cortex into regenerating peripheral nerves of adult rats were analyzed during the first 3 weeks after transplantation. On day 11 of gestation, donor fetuses were removed from one uterine horn of pregnant Sprague-Dawley rats and pieces of cortex (1.0 X 0.5 mm) were dissected from them for transplantation. Fetuses and normally delivered pups from the other uterine horn were used as age-matched controls. In 45 adult male Sprague-Dawley rat hosts (200 to 300 g), the epineurium of the nerve to the biceps femoris muscle was crushed and incised, the perineurium minced, and E11 donor cortex was injected into the nerve. At 1 to 7 days postimplantation (DPI), undifferentiated neuroepithelial cells were dispersed or in oval neuroepithelial-like structures throughout the regenerating nerve. At 7 to 14 DPI, neurons and neuroglia were differentiating and interspersed among fascicles of regenerating host axons. At 14 to 21 DPI, aggregates of differentiated neurons surrounded by neuropil containing a rich synaptic bed were interspersed with regenerated host peripheral axons. Fetal cortical implants survived, increased in size, and differentiated throughout the postoperative period, matching their timed controls. PMID- 4018206 TI - Temperature effects on the kinetics of force generation in normal and dystrophic mouse muscles. AB - The kinetics of isolated extensor digitorum longus and soleus muscles from normal and genetically dystrophic (129/ReJ dy/dy) mice were studied at temperatures from 8 to 38 degrees C. The rate constants for the exponential rise of tetanic force and for the exponential decay of force during an isometric twitch or short tetanus were similar in normal and dystrophic soleus muscles, but the decay rates were significantly reduced in dystrophic extensor digitorum longus muscles. The temperature dependence for several rate constants for isometric twitches and tetani was similar in all muscles studied, suggesting that the same rate limiting processes apply to fast and slow, normal and dystrophic muscles. Thus, the contractile proteins and those in the sarcoplasmic reticulum of dystrophic muscle are probably normal. The slower relaxation phase in dystrophic extensor digitorum longus muscles is compatible with a reduction in Ca2+-pumping sites in the sarcoplasmic reticulum, perhaps secondary to a change in motor unit composition. Some changes in the temperature dependence for measured times, toward those of soleus muscles, is consistent with the increased proportion of slow twitch motor units in dystrophic extensor digitorum longus muscles. PMID- 4018207 TI - Cholinergic regulation of neocortical spindling in DBA/2 mice. AB - Brief episodes of high-amplitude, bilaterally synchronous, seven-cycles-per second spindles appear in the EEG of DBA/2 inbred mice during active waking, quiet waking, and slow-wave sleep. They do not occur during waking in C57BL/6 mice. This difference might result from differences in acetylcholine-mediated arousal as nicotine powerfully blocks brief spindle episodes in awake DBA/2 mice. The following results are reported. (i) Physostigmine (0.1 and 0.3 mg/kg, i.p.) desynchronized the EEG and produced behavioral immobility, but did not block brief spindle episodes in free-moving DBA/2 mice. (ii) Atropine (1.0 mg/kg, i.p.) reduced arousal and provoked slow waves without facilitating brief spindle episodes. (iii) Mecamylamine (1.0 mg/kg, i.p.) weakly activated spindles without producing any noticeable behavioral alterations. Because these treatments had little effect on spindle occurrence, the action of nicotine in brain stem transected DBA/2 mice was investigated. Nicotine (1.0 mg/kg, i.p.) had no effect on brief spindle episodes released by rostropontine transection but powerfully blocked those provoked by pentylenetetrazol (20 mg/kg, i.p.) in midpontine transected mice. Hence nicotine's antispindling action may be mediated in the rostral pons. As both nicotine and physostigmine produce behavioral immobility and EEG activation in free-moving DBA/2 mice, but only nicotine inhibits cortical spindling, the mechanisms that produce EEG desynchronization are probably not identical to those that prevent spindling. They may, though, be linked, parallel processes that are somehow dissociated in DBA/2 mice. PMID- 4018208 TI - Developmental neuron cell death in dystrophic and normal chickens. AB - The numbers of motoneurons in the brachial lateral motor columns were determined from the 6th embryonic day through the 5th week posthatching in age-matched dystrophic and normal chickens. The overall magnitude of cell loss was not significantly different between the dystrophic and normal strains. However there was a trend toward more motoneurons in the brachial lateral motor columns of dystrophic embryos and posthatch chickens which was found to be statistically significant at the 8th and 9th days of embryonic life. These observations are taken to suggest that, in addition to strain differences unrelated to the dystrophic gene, there may exist a temporal delay in developmental neuron cell death in dystrophic chick embryos that may be secondary to the primary defect within the dystrophic muscle. PMID- 4018209 TI - Chlordimeform produces contrast-dependent changes in visual evoked potentials of hooded rats. AB - Previous experiments found that acute exposure to the insecticide/acaricide, chlordimeform (CDM), produced large increases in the amplitude of pattern reversal evoked potentials (PREPs) without changing the amplitude of flash evoked potentials (FEPs) in the same rats (W. K. Boyes and R. S. Dyer, Exp. Neurol. 86: 434-447, 1984). Current work investigated the influence of physical characteristics of the evoking stimuli on the action of CDM. Adult male Long Evans rats with epidural visual cortex electrodes were used. In experiment 1, PREPs were elicited with alternating gratings having equal contrast (99%) and a square wave spatial luminance profile at several spatial frequencies. Rats treated 1 h previously with 40 mg/kg CDM had increased PREP amplitudes at 0.1, 0.2, and 0.4 cycles per degree (cpd), but not at 0.8 cpd. No changes were found after 5 mg/kg CDM. In experiment 2, PREPs were elicited with gratings oriented at 0 degrees (horizontal), 45 degrees, 90 degrees, or 135 degrees. Treatment with 40 mg/kg CDM increased PREP amplitudes and latencies regardless of orientation. In experiment 3, FEPs elicited with strobe flashes spanning four log units of intensity showed a small but significant CDM dose X intensity interaction on P2N2 peak-to-peak amplitude. In experiment 4, PREPs were elicited with alternating gratings having a sinusoidal spatial luminance profile, spatial frequency of 0.2 or 0.8 cpd, and contrast ranging from noise levels to 65%. Rats treated with 40 mg/kg CDM showed increased peak-to-peak amplitudes only at 0.2 cpd and only at contrast values above 10%. The failure of CDM to alter PREPs at 0.8 cpd was attributed to low contrast sensitivity at that spatial frequency. The results demonstrated that the action of CDM on visual evoked potentials was dependent on the amount of contrast in the stimulus pattern, and suggested that CDM alters the encoding of visual contrast. PMID- 4018210 TI - Cell body responses to axonal injury: traumatic axotomy versus toxic neuropathy. AB - To compare the evolution of cell body responses to two different types of axonal injuries--sciatic nerve crush (axotomy) and chronic 2,5-hexanedione-induced neuropathy--we studied rat lumbar dorsal root ganglion neurons with light microscopy and morphometry. Compared with control neurons, axotomized cells showed early (1 day) increases in the frequencies of two responses, nuclear eccentricity and Nissl body displacement, and later (4 day) increases in average satellite cell nuclei and decreases in perikaryal diameters. In toxin-induced axonal degeneration, there were similar patterns of defined alterations, although the evolution progressed over weeks and the response magnitudes were smaller. We conclude that the two experimental conditions show basic morphologic similarities, implying cell body reorganization in toxic axonopathy may be a response to axonal dysfunction or degeneration. PMID- 4018211 TI - Cingulate cortex response to electrical stimulation of the mediodorsal thalamic nucleus. AB - Electrical stimulation of the lateral, parvocellular part of the mediodorsal thalamic nucleus of the rabbit was found to evoke field potentials and drive single cells in the anterior cingulate cortex. Furthermore, the laminar distribution of the field responses and the population of effected cells were dependent on the frequency of the stimulation. Excitatory current sinks were produced in layers I and III (primary layers of mediodorsal input) only when the stimulus frequency was in the theta range (6 to 8 Hz); the majority of cells were reliably driven only by stimulation within this range. Lower-frequency stimulation, e.g., 0.5 Hz, produced a current sink in layer V. Cells that were driven at low frequencies might be antidromically activated. The study suggests that modulation of mediodorsal outflow in the theta range may be necessary for effective information transfer to the cortex. PMID- 4018212 TI - Nucleolar changes in goldfish retinal ganglion cells in response to an optic nerve lesion are not perturbed by a second lesion. AB - The reaction of the goldfish retinal ganglion cells to optic nerve crush, as indicated by an increase in nucleolar incidence 4 to 5 days after this lesion, was not significantly affected if a second nerve crush was made within 3 days after the first. This appears to rule out axon sprouting as the initiating event for the cell body reaction to axotomy. PMID- 4018214 TI - Striatal dopamine after cortical injury. AB - After right or left unilateral sensorimotor cortex ablation or a sham operation, dopamine concentrations were assayed in the right and left striatum of rats. In the sham-operated animals, a greater amount of dopamine was found in the left striatum compared with the right. Right or left sensorimotor cortex injury reduced dopamine in both striata. Right hemisphere lesions produced a greater loss of dopamine in the right striatum compared with the effect of a left lesion on dopamine in the left striatum. The results support the hypothesis of an asymmetric response to cortical injury. PMID- 4018213 TI - Involvement of cortical, thalamic and midbrain reticular formation neurons in spike and wave discharges: extracellular study in feline generalized penicillin epilepsy. AB - Extracellular activity of single units, simultaneously recorded in cortex, thalamus, and midbrain reticular formation was investigated during feline generalized penicillin epilepsy. The firing activity of neurons recorded in the cortex was invariably and consistently enhanced in coincidence with the positive peak and the positive-negative transient of the "spike" of the spike and wave complex, and it was greatly decreased during the wave. In the nonspecific thalamic nuclei three classes of neurons were identified according to their patterns of activity during the spike and wave complex: (i) neurons behaving like cortical units, (ii) neurons with enhanced firing activity during the wave and a decreased activity during the "spike," and (iii) unmodified neurons. In the nucleus lateralis posterior neurons of the third class were not found. Most midbrain reticular neurons could be classified in the same three classes of the nonspecific thalamic nuclei; however, 11% of those units increased their activity 20 to 30 ms earlier than did the cortical units (class IV). Investigation of the activities of all these neuronal populations immediately prior to a spike and wave discharge showed that the rhythmic cycle of excitation-inhibition commenced earlier in the cortical neurons than in any other subcortical neuron. Moreover, there were some nonspecific thalamic neurons of class II with an inhibitory phase exactly coincident with the activation of class IV midbrain reticular neurons. These data suggest (i) a leading role of cortical neurons in initiating and maintaining a spike and wave burst; (ii) the involvement of a corticothalamocortical circuit in timing the bursts, and (iii) an accessory reticulothalamic loop also involved in regulating the intraburst frequency of the spike and wave complex. PMID- 4018215 TI - Schistosoma mansoni: challenge attrition during the lung phase of migration in vaccinated and serum-protected rats. AB - Serum harvested from Sprague-Dawley rats twice vaccinated with gamma-irradiated cercariae of Schistosoma mansoni is able to protect naive recipients against a challenge infection, but the challenge parasites are susceptible to immune elimination over a very short period of time. Thus, vaccinated rat serum protects recipients against a percutaneous cercarial challenge when transferred on Day +5 but not Day 0 and protects recipients against a tail vein challenge with 5-day old lung worms when transferred on Days 0 or +1, but not Days +4 or +5. Rats challenged with lung worms via the tail vein and given serum on Day +3 exhibit approximately half the protection expressed by counterparts that received serum on Day 0. However, vaccinated rat serum does not protect naive recipients against a lung worm challenge introduced directly into the liver. These data indicate that immune elimination of challenge parasites in the vaccinated rat model is site-dependent rather than stage-dependent, and most probably occurs during the lung phase of parasite migration. PMID- 4018216 TI - Schistosoma mansoni: effects of in vitro serotonin (5-HT) on aerobic and anaerobic carbohydrate metabolism. AB - The effect of Serotonin on carbohydrate metabolism, excreted end products, and adenine nucleotide pools in Schistosoma mansoni was determined following 60 min in vitro incubations under air (= 21% O2) and anaerobic (95% N2:5% CO2) conditions. In the presence of 0.25 mM Serotonin, glucose uptake increased by 82 84% and lactate excretion increased by 77-78%; levels of excreted lactate were significantly higher under aerobic than under anaerobic conditions. The tissue pools of glucose, hexosephosphates, fructose 1,6-bisphosphate, pyruvate, and lactate were significantly increased under anaerobic conditions compared to air incubation; the presence of Serotonin decreased tissue glucose pools and increased the size of the pyruvate and lactate tissue pools. The glycolytic carbon pool was significantly greater under anaerobic than under aerobic conditions, irrespective of Serotonin. Serotonin increased adenosine 5' diphosphate and adenosine 5'-monophosphate levels under aerobic conditions; neither Serotonin nor gas phase significantly affected total adenine nucleotide levels or the adenylate energy charge. Serotonin increased energy requirements by S. mansoni due to increased muscle contractions; demand was met by enhanced rates of carbohydrate metabolism. Irrespective of gas phase, 74-78% of available carbohydrate was converted to lactate. In the presence of Serotonin, conversion of glucose to lactate was reduced to 63-67%. In view of the requirements by S. mansoni for an abundant supply of glycoprotein and glycolipid precursors for surface membrane renewal, it is suggested that carbohydrate (glucose and glycogen) that was not converted to lactate may have been incorporated into biosynthetic processes leading to membrane synthesis. PMID- 4018217 TI - Trichinella spiralis: nonspecific resistance and immunity to newborn larvae in inbred mice. AB - The implantation and development of intravenously injected Trichinella spiralis newborn larvae were examined in different strains of inbred mice by determining muscle larvae burden. This was compared to the numbers of muscle larvae that established after a natural infection during which a quantitative assessment of intestinal newborn larvae production was made. In most inbred strains of mice, newborn larvae do not all successfully implant in muscle. Mice of the DBA/1 strain are the most resistant to successful implantation, and C3H mice are the most permissive. This pattern is evident in the strains studied whether newborn larvae are injected intravenously or are produced by intestinal adults. Thus, after a natural infection, 100% of intestinally produced newborn larvae implanted in C3H mice, whereas in NFR 68% and DBA/1 mice 62% successfully matured in muscle. Immunity to newborn larvae could be demonstrated as early as 10 days after exposure to this stage of the life cycle. This immunity was protective against a complete challenge infection given 9 days after newborn larvae had been injected intravenously. Protection against newborn larvae was identical in male and female mice or in mice from 1 to 9 months of age. We conclude that there are two mechanisms by which mice impair newborn larvae establishment or development in muscle. The first appears to be nonimmunological (non-specific resistance), and the second is immunological. Genetically determined variation in strain specific expression is apparent with both mechanisms. In strains displaying high intrinsic "resistance" (DBA/1), this process is likely to account for most of the 38% reduction in newborn larvae establishment in a primary infection. However, immunity against newborn larvae develops quickly enough to have a significant effect on migratory larvae in primary infections where adults persist in the intestine (e.g., the B10 congenic mice), or when high adult worm burdens delay adult worm rejection. Muscle larvae burden, therefore, reflects systemic nonspecific resistance to newborn larvae as well as immunological processes that occur in the intestine and systemically. PMID- 4018218 TI - Heligmosomoides polygyrus: inoculum size and glucose, ion, and gas fluxes in the small intestine of mice. AB - Female CDI mice were inoculated with 10, 50, 100, 250, or 500 larvae of Heligmosomoides polygyrus. At Days 7, 9, and 12 after infection, the anterior third of the small intestine was perfused using an in vivo technique. The distribution of worms in the mouse intestine was determined after 7, 9, and 12 days. All worms that were recovered were from the proximal half of the small intestine. When compared to uninfected controls, there was a significant increase (+56%) in glucose absorption of the small intestine at Day 7 after infection with inocula of 50 and 100 larvae; at Day 9, glucose absorption was significantly increased with a 10-larvae inoculum. A decrease in glucose absorption occurred at Days 7 and 9 after infection with a 500-larvae inoculum. Net water absorption was significantly increased (+183%) with the 50- and 100-larvae inocula at Day 7, but was significantly reduced at Day 9 after infection with the 50-, 100-, 250-, and 500-larvae inocula. Both Cl- and Na+ absorption were significantly increased with the 50-, 100-, and 250-larvae inocula at Day 7 after infection; at 9 and 12 days, there was significant net secretion of both ions. In control mice, there was net secretion of K+, while with the 50-, 100-, and 250-larvae inocula on Day 7 there was significant net absorption of K+ ions.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4018221 TI - The use of excised, pressurized blood vessels to study the physiology of vascular smooth muscle. PMID- 4018220 TI - Current problems in smooth muscle mechanics. PMID- 4018219 TI - Velocity and myosin phosphorylation transients in arterial smooth muscle: effects of agonist diffusion. AB - Transients in myoplasmic [Ca2+] and in phosphorylation of the 20,000 dalton light chain of myosin have been reported following stimulation of vascular smooth muscle by various agonists. Since these transients are rapid compared with the time required to attain a steady-state stress, agonist diffusion rates may be a significant limitation in activation. The purpose of this study was to estimate the effect of agonist diffusion rates on the time course of activation as assessed by mechanical measurements of stress development and isotonic shortening velocities and by determinations of the time course of myosin phosphorylation. The approach was to measure these parameters in K+ -stimulated preparations of the swine carotid media of varying thicknesses and to estimate the theoretical contributions imposed by diffusion rates and the presence of a diffusion boundary layer surrounding the tissue. The results show that the time course of parameters which are tissue averages such as stiffness, active stress, and myosin phosphorylation is dominated by agonist diffusion rates. The sequence of events involved in excitation-contraction coupling including agonist actions on the cell membrane, Ca2+ release, activation of myosin light chain kinase, and cross-bridge phosphorylation appear to be very rapid events compared with stress development. Estimates of unloaded or lightly loaded shortening velocities which are not simple tissue averages appear to provide an improved estimate of activation rates. PMID- 4018223 TI - Interhemispheric asynchrony of the sleep EEG in northern fur seals. AB - In northern fur seals the two brain hemispheres can generate the EEG slow waves during sleep not only simultaneously, as in all the terrestrial mammals investigated, but also independently as in dolphins. PMID- 4018222 TI - Juvenile hormone titre and regulation in the cockroach Diploptera punctata. AB - Titres of juvenile hormone (JH) have been determined in both hemolymph and whole body extracts of female Diploptera punctata during the first gonotrophic cycle using a method employing gas chromatography/mass spectrometry for qualitative and quantitative analysis. JH III is the sole JH found in both adult and last instar D. punctata. Maximum values of approximately 1500 ng/ml (approximately 6 microM) were observed at the middle of the gonotrophic cycle, when basal oocyte growth rate was greatest. Changes in rates of JH release in vitro by corpora allata paralleled closely the changes in JH titre, suggesting that biosynthesis is a major regulator of titre. JH levels per animal were calculated from observed JH titres, and at certain time points in the gonotrophic cycle JH obtained from analysis of whole bodies were significantly greater than those predicted from hemolymph titres. These results suggest the existence of a nonhemolymph JH pool in D. punctata. Decay in JH titre after allatectomy of 5 day females has also been studied. Following a rapid initial decline, the rate of decay slowed appreciably 4 h post-operation. Thus, use of a first-order rate constant to estimate half-life of JH significantly underestimated the longevity of the hormone. The apparent persistence of JH following allatectomy may be due to the existence of a nonhemolymph JH pool. PMID- 4018224 TI - Electromyographic responses elicited by cutaneous and mixed nerve stimulation in human tibialis anterior muscle. AB - The rectified and averaged myoelectrical responses of the anterior tibial muscle to stimulation of the posterior tibial, peroneal and sural nerves at the ankle were recorded during a weak isometric contraction in man. The stimulation of the posterior tibial nerve elicited two excitatory phases (short and long latency excitations) at 40 ms and 78 ms latencies, respectively, separated by a phase of reduced activity. With peroneal and sural nerve stimulation such triphasic responses were less consistent; only a monophasic inhibitory response occurred in some recordings. These results indicate that well-identifiable responses with distinct latencies can be obtained in human leg muscle with cutaneous and mixed nerve stimulation distal to the muscle. PMID- 4018225 TI - A comparison of the effects of the optical isomers of isoproterenol on energy metabolism in a mouse sarcoma. AB - Disturbance to energy production in the S180 sarcoma (CB) by optical isomers of isoproterenol was assessed from altered adenine nucleotide levels at 1 h. The L isomer almost halved the ATP level and lowered the energy charge significantly; the D-isomer was inactive. Dependence of tumor injury on cytochrome P-450 activity appears unlikely. PMID- 4018226 TI - The effects of vitamin A nutritional status on glutathione levels and microsomal lipid peroxidation in rat lung. AB - In vitamin A-deficient rats, the glutathione level in lung was diminished and microsomal lipid peroxidation much increased. In vitamin A-loaded animals, however, both were depressed below control. Thus vitamin A protection against lipid peroxidation is independent of glutathione. PMID- 4018227 TI - Stereological analysis of lipofuscin in the central nervous system of Torpedo marmorata: correlation with superoxide dismutase distribution. AB - It was observed that superoxide dismutase was inversely proportional to the amount of lipofuscin present in the various anatomotopographical areas of the Torpedo marmorata central nervous system. These results support the theory that age pigments are a product of free lipoperoxidation induced by free radicals. PMID- 4018228 TI - Role of the delta 8 double bond of agroclavine in lysergic acid amide biosynthesis by Claviceps purpurea. AB - Agroclavine, given to actively-growing sclerotial tissue of a strain of Claviceps purpurea which can not normally elaborate ergot alkaloids, was transformed by this tissue into lysergic acid amide with overall efficiency of approximately 40%. By contrast, festuclavine (8,9-dihydro-agroclavine) was not transformed, indicating specificity in the mechanism of lysergyl biosynthesis. PMID- 4018229 TI - Comparative analysis of phospholamban phosphorylation in crude membranes of vertebrate hearts. AB - Phospholamban, a sarcoplasmic reticulum phosphoprotein, is present in the hearts of mammalian, avian, amphibian, and fish species. Phylogenetic changes are indicated by marked differences among species in cardiac phospholamban content and by the absence of Ca2+/calmodulin-dependent phospholamban phosphorylation at an early developmental stage. PMID- 4018230 TI - Acetylcholine induced endothelial-dependent vasodilation increases as artery diameter decreases in the rabbit ear. AB - Isolated resistance vessels in the rabbit ear preconstricted with histamine were relaxed by acetylcholine by a proportionately greater amount than the central ear artery. The relaxation was antagonized by atropine and also by endothelium removal. Our studies represent the first direct evidence that endothelium dependent dilation can occur in resistance vessels. PMID- 4018231 TI - Comparison of counterimmunoelectrophoresis (CIE), latex agglutination (LA) and staphylococcal coagglutination (COAG) in pneumococcal antigen detection in vitro. AB - CIE was compared to agglutination assays employing commercial kits (Directigen, Phadebact), as well as our own LA and COAG reagents, in detection of pneumococcal capsular polysaccharide (PCP) antigens in vitro. Directigen provided the most sensitive assay. CIE was of comparable sensitivity except for PCP antigen types 7 and 14. PMID- 4018233 TI - Injection of a soluble sperm fraction into sea-urchin eggs triggers the cortical reaction. AB - Fertilization membranes form around unfertilized sea-urchin eggs after microinjection of a soluble spermatozoa fraction isosmotic with seawater. This demonstrates that the spermatozoon contains a chemical that triggers an increase in cytosolic calcium, leading to exocytosis of cortical granules. It also demonstrates that the triggering mechanism does not require an externally activated egg-membrane process. Further experiments show that the chemical trigger is not calcium. PMID- 4018232 TI - Endogenous copper is cytotoxic to a lymphoma in primary culture which requires thiols for growth. AB - With the use of bathocuproine sulfonate, a copper-specific chelator as an indicator, we have demonstrated that copper ions, present as a natural medium constituent are toxic to the growth of a lymphoma in primary culture and are principally responsible for the growth requirement of mercaptoethanol and other thiols. By chelating trace copper normally present in the medium, bathocuproine sulfonate retarded the oxidation of cysteine to poorly utilized cystine, thus permitting its direct utilization by the cells for growth. PMID- 4018234 TI - Decomposition of toxic and environmentally hazardous 2,3,7,8-tetra-chlorodibenzo p-dioxin by gamma irradiation. AB - The decomposition of the toxic and environmentally hazardous 2378-TCDD by gamma irradiation was studied and successfully used to decontaminate laboratory wastes containing small quantities of this chemically and biologically stable compound. The method makes use of gamma irradiation from a commercial 60cobalt facility at high dose levels (1000 kGy) to break down the compound into nontoxic products. Irradiation also decomposed 2378-TCDD in contaminated soil from the Seveso accident. PMID- 4018236 TI - The physiology of smooth muscle: an interdisciplinary review. A tribute to Edith Bulbring. Part II. PMID- 4018237 TI - A developmental model for family systems. AB - This paper reviews the historical context of concepts of development and some of the problems of applying them to family systems. A model of family systems development is presented that emphasizes changes in family shape through the individual life cycle. Some clinical uses of the model are described. PMID- 4018235 TI - Improved separation at low temperature of glycoproteins by Con A-Sepharose affinity chromatography in the presence of sodium dodecyl sulfate (SDS). AB - The Con A-Sepharose affinity chromatography of glycoproteins was even more effective at 4 degrees C than that at room temperature (26-28 degrees C) in the presence of sodium dodecyl sulfate (SDS). Application of this methodology to the separation of several glycoproteins from SDS-solubilized membrane proteins in rat cerebellum, including a glycoprotein characteristic of the Purkinje cells, was successful. PMID- 4018238 TI - From general laws to singularities. AB - This article comprises several sections. The first is devoted to an explanation of a number of notions stemming from work by Ilya Prigogine and others on open systems far from equilibrium. As a result of this work, I have been able to stand back from the traditional approach employed in family therapy, that of open systems at equilibrium (the theory of Ludwig von Bertalanffy). The second section describes a clinical example based on elements close to Prigogine's theories. In the third part I develop an approach that--although continuing to draw on Prigogine's work--is much more closely linked to the research I have carried out with Felix Guattari over recent years. In this part I attempt to study a level that, in my view, has too often been left outside the field of inquiry: that of couplings between "singularities" of members of the family system and the therapist. A clinical case is presented in which this "semiotic" level, as Guattari terms it, is used together with that of the "intrinsic rules" of the system. Finally, I propose a few avenues of inquiry and research on the basis of the concepts presented. PMID- 4018239 TI - Paradox and polarity: the Tao of family therapy. AB - Taoism is a Chinese spiritual tradition whose central metaphors concern polarity, paradox, and the natural process of change. Taoist ideas offer a particularly useful framework for understanding paradoxical interventions, the stance of the paradoxical therapist, and the new epistemology emerging in the field. The relevance of three Taoist metaphors for family therapists is discussed: polarity, cyclical change, and Wu Wei (noninterference). PMID- 4018240 TI - Methods for analyzing marital conflict discourse: implications of a systems approach. AB - A large number of studies of family and marital conflictual interaction purport to describe relational processes, yet close examination reveals a scarcity of process analyses. Many studies are interactional or systemic in name only. Three basic criteria are proposed as necessary for the development of a systems methodology: observable, sequential, system-level behavioral descriptions. A methodological review of the literature reveals that the first criterion yielded the most abundant set of methodologies. Application of the second criterion resulted in a much smaller number, which after the third criterion dwindled to a mere handful. This review does not focus on the substantive results of these investigations but rather on the research criteria, strategies, and issues that need to be addressed if process-oriented measures are to be developed for the study of interpersonal systems. PMID- 4018241 TI - Pragmatics in the measurement of family functioning: an interpretive framework for methodology. AB - The issue of the cross-method comparison of concepts that describe family functioning is addressed by means of an empirical investigation of two methods of family assessment. The examination focuses on a consideration of the functional, or pragmatic, aspects of subjects' responses through a comparison of a self report and an observational method whose associated concepts appear to be similar. Little predicted association based on conceptual similarity is noted. An interpretive framework is developed suggesting that the outcomes of empirical method comparisons may be usefully considered in terms of the pragmatic aspects of subjects' responses or the way in which subjects may be using their responses, based on their inferences regarding the interpersonal context associated with each method. PMID- 4018242 TI - Alternative strategies for creating "relational" family data. AB - A major problem facing family clinicians and researchers is creating data that will reflect the family as a unit. To address this problem, we present a framework for family assessment based on three measurement strategies: individual family member assessment, relational family assessment, and transactional family assessment. Within this context, we present several categories of methods for combining individual family member data into "relational" scores that reflect the couple or family as a unit. The problems and benefits of each method are presented, and it is suggested that the choice of method is dependent upon the content of the assessment, the theory underlying the content, and the statistical properties of the individual family member scores. PMID- 4018243 TI - A factor analysis of self-report measures of family functioning. AB - Four well-known, self-report measures of family functioning were serially examined in order to identify a limited set of reliable concepts for describing families. Following the completion of four separate data collection procedures, a 75-item scale comprising 15 dimensions of family functioning was constructed. The dimensions appear reasonably independent of each other and have satisfactory psychometric properties. An initial effort to validate the scales was undertaken by contrasting scale scores obtained from descriptions of intact families with those obtained from descriptions of families that subsequently were disrupted by separation and divorce. Significant differences in scale scores were obtained on 12 of the 15 dimensions of family functioning. The 15 dimensions of family functioning could be subsumed under the three general headings suggested by Moos, Insel, and Humphrey (14)--relationship dimensions, personal growth or value dimensions, and system maintenance dimensions. PMID- 4018244 TI - The social construction of unreality: a case study of a family's attribution of competence to a severely retarded child. AB - Some families develop unusual or extreme versions of reality and sustain them in the face of a torrent of ostensibly discrediting and disconfirming information. Although the psychological dynamics and functions of such shared constructions have been amply considered, little is known about the routine transactions through which these unusual versions of reality are created and maintained. This paper examines the "reality work" of a family that attributed high levels of performance and competence to the severely retarded youngest child. Observation of videotaped interaction between family members and the child revealed practices that presupposed, "documented," and sustained the family's version of the child's competence. The practices are similar to those characteristic of interaction between adults and preverbal children. The implications of this similarity for the analysis of cases of folie a famille are discussed. PMID- 4018245 TI - The debate: a strategic technique. AB - This paper describes the work of a strategic team that came out from behind the one-way mirror. A debate among the team is enacted before the family as a strategy for change. The case of a family that refused to provide information illustrates an application of this method. The debate among the therapists represents a dilemma that is a strategically constructed isomorph of the family situation. From this position, therapists have the option of changing levels between themselves and the family, asking the family to help solve the therapists' dilemma so that they in turn can be free to help the family. The combination of the debate and the change of levels between the therapists and the family creates a therapeutic neutrality for the family. From their meta position, they observe the therapists' struggle to solve the family's problem, which is re presented as a problem among the therapists. This perspective offers the family the choice of more adaptive solutions to their own dilemma. PMID- 4018246 TI - Sharing the holocaust experience: communication behaviors and their consequences in families of ex-partisans and ex-prisoners of concentration camps. AB - This study concerns the manner in which the traumatic events suffered by the parent in the Nazi holocaust are communicated to the second generation born after the Second World War. Additionally we investigated the effects of differences in wartime experiences on subsequent communication behaviors. Communication behaviors in families whose parents had been prisoners in concentration camps were compared with those of families who had displayed active resistance (i.e., were partisans) during the Second World War. The data indicate greater legitimacy and openness in discussing holocaust-related issues in the homes of ex-partisans than in the homes of ex-prisoners in concentration camps. Also, sons and daughters of the former group have better knowledge of the holocaust and hold more favorable attitudes than do sons and daughters in the second group. The implications of these findings are discussed. PMID- 4018247 TI - Hyperpigmentation induced by furocoumarins. PMID- 4018248 TI - [Pharmacokinetics of naftazone in the dog]. PMID- 4018249 TI - [Corynebacterium kutscheri infection in the Wistar rat]. PMID- 4018250 TI - Studies on annelated 1,4-benzothiazines and 1,5-benzothiazepines. I. Synthesis of 4H-s-triazolo[3,4-c]-1,4-benzothiazine and derivatives with potential CNS activity. AB - As a part of a program toward the synthesis and the pharmacological studies on annelated 1,4-benzothiazines and 1,5-benzothiazepines, a number of 4H-s triazolo[3,4-c]-1,4-benzothiazine derivatives were prepared and tested for their CNS activity. The syntheses of the new tricyclic compounds (VII) were performed via the 2H-1,4-benzothiazine-3(4H)-thiones (II) which were obtained by Lawesson's thiation of lactams (I). Compounds (II) and their S-methyl-thioethers (III), quantitatively obtained by PTC method, were reacted with acylhydrazines to give the title compounds. Some triazolobenzothiazines (VII) were also prepared from 3 hydrazinoderivatives (IV) by cyclization with either an aliphatic acid or the corresponding orthoesther. PMID- 4018251 TI - [Synthesis of N-phenylmaleimides. Kinetics of the antifibrillatory action of a derivative of procainamide]. AB - The synthesis of some N-phenylmaleimides is described. Among them, reaction of (III a) with procainamide afforded an available prodrug (III c). Antiarrhythmic activity of (III c) was compared with that of procainamide in mice. PMID- 4018252 TI - The activation of cellulases from different sources by actin. AB - Actin has been shown to be a potent activator of the enzymatic hydrolysis of cellulose, its addition to the reaction mixture leading to an increase in the hydrolysis rate of up to 6-7 fold. The action of actin is directed primarily towards endoglucanases of cellulase complexes. The degree of activation varies in relation to the cellulases from different microbial sources. The activation of the enzymatic hydrolysis of an insoluble cellulose by actin does not affect the Michaelis constant but increases the maximum velocity of the reaction. Increasing the actin concentration leads to a linear increase in the activation effect which indicates a rather poor binding of actin with the cellulases under study. PMID- 4018253 TI - Selective expression of glutathione transferase isoenzymes in chemically induced preneoplastic rat hepatocyte nodules. AB - Isoenzymes of glutathione transferase were shown to occur at selectively altered levels in rat hepatocyte nodules produced by 2-acetylaminofluorene treatment. Changes were measured by different substrates, antibodies raised against purified glutathione transferases, and by purification of the major isoenzymes. Isoenzymes composed of subunits 1, 2 and 3, expressed in normal liver tissue, all occurred at increased concentrations in nodules, whereas the level of transferase 4-4 was decreased. The most conspicuous change was the appearance of glutathione transferase 7-7 (or transferase P), the concentration of which in negligible in normal liver. PMID- 4018254 TI - 1H NMR detection of cerebral myo-inositol. AB - A previously unassigned group of prominent multiplets of the 360 MHz 1H NMR spectrum of acid stable metabolite extracts from rat brain is shown to arise from free myo-inositol. This conclusion is derived from a systematic analysis of the high-resolution 1H NMR spectra of brain acid extracts, in which appropriate conditions and optimal proton signals have been selected for the quantitative analysis of up to 15 metabolites. Developmental variations in the cerebral content of myo-inositol could be readily detected using this approach, which provides a novel alternative to study myo-inositol metabolism under physiological or pathological conditions. PMID- 4018255 TI - Quantitative measurement of the total, peroxyl radical-trapping antioxidant capability of human blood plasma by controlled peroxidation. The important contribution made by plasma proteins. AB - Plasma obtained from fasted humans has been analysed for total radical-trapping antioxidant content by subjecting it to controlled peroxidation using the thermal decomposition of water-soluble azobis (2-amidinopropane hydrochloride) at 37 degrees C to produce peroxyl radicals at a known, steady rate. It is found that the total radical-trapping antioxidant content is rather similar for the 7 subjects that have been tested and, furthermore, it is 10-20-times larger than the effect attributable to vitamin E alone. Although it is shown that urate and ascorbate augment the contribution from vitamin E, their contributions (21-34 and 0-2%, respectively) still leave 57-73% of the total antioxidant content unaccounted for. Evidence is presented to show that this previously unrecognized large reserve of antioxidant capacity is attributable to the plasma proteins. PMID- 4018256 TI - 5-Fluoroorotate: a new liposome-dependent cytotoxic agent. AB - The potency of 5-fluoroorotate for inhibition of L929 or CV1-P cell growth is increased by encapsulation in negatively charged liposomes. The optimal liposome composition is dipalmitoylphosphatidylglycerol: cholesterol, 67:33. Unextruded large unilamellar liposomes are the optimal size for delivery. This compound is the second transport-negative drug which we have found to exhibit liposome dependent delivery. PMID- 4018257 TI - Isolation and structural characterization of the smaller-size oligosaccharides from desialylated human kappa-casein. Establishment of a novel type of core for a mucin-type carbohydrate chain. AB - Alkaline borohydride reductive cleavage (beta-elimination) of desialylated human kappa-caseinoglycopeptide resulted in the release of a series of oligosaccharides. The smaller-size compounds among them were purified to virtual homogeneity by gel filtration followed by high-performance liquid chromatography. The structures of 9 oligosaccharides were determined by 1H-NMR spectroscopy in conjunction with sugar analysis. The tetrasaccharide Gal beta(1----3)[Gal beta(1- --4)GlcNAc beta(1----6)] GalNAc-ol and various partial structures thereof were characterized. Notably, the disaccharide GlcNAc beta(1----6)GalNAc-ol and the trisaccharide Gal beta(1----4)GlcNAc beta(1----6)GalNAc-ol were identified; they represent a novel type of core structure for mucin-type carbohydrate chains, namely a peptide-linked GalNAc that is mono-substituted at C-6. In addition, some oligosaccharides ending in GlcNAc-ol could be characterized. Their possible origin is discussed. PMID- 4018258 TI - Tumour-host metabolic interaction and cachexia. AB - Cachexia is a terminal metabolic problem observed in a wide variety of tumours. In this article I propose that the syndrome is a direct consequence of the common feature to all malignant tumours: growth. I suggest that the requirement for essential amino acids can be used as the unifying principle that links the tumour to the two main components of cachexia: muscle wastage and anorexia. This underlying factor is usually clouded by the overlapping of individual tumour characteristics. PMID- 4018259 TI - A metabolic switch produced by enzymically interconvertible forms of an enzyme. AB - A system of enzymically interconvertible enzyme forms (interconversion cycle) is known to increase the sensitivity to regulators. Here it is shown that this system may also provide a discrete switching mechanism in which the response is maintained when the stimulus is removed. These switches may be important in producing discontinuous metabolic changes such as those associated with cell differentiation. PMID- 4018260 TI - Use of monoclonal antibodies to analyse the expression of a multi-tubulin family. AB - We have used a panel of monoclonal antibodies in a study of the expression of multiple tubulins in Physarum polycephalum. Three anti-beta-tubulin monoclonal antibodies, DM1B, DM3B3 and KMX-1 all reacted with the beta 1-tubulin isotypes expressed in both myxamoebae and plasmodia. However, these antibodies showed a spectrum of reduced reactivity with the plasmodial beta 2-tubulin isotype - the competence of recognition of this isotype was graded DM1B greater than KMX-1 greater than DM3B3. The anti-alpha-tubulin monoclonal antibody, YOL 1/34 defined the full complement of Physarum alpha-tubulin isotypes, whilst the anti-alpha tubulin monoclonal antibody, KMP-1 showed a remarkably high degree of isotype specificity. KMP-1 recognises all of the myxamoebal alpha 1-tubulin isotypes but only recognises 3 out of the 4 alpha 1-tubulin isotypes expressed in the plasmodium (which normally focus in the same 2D gel spot). KMP-1 does not recognise the plasmodial specific alpha 2-tubulin isotype. This monoclonal antibody reveals a new level of complexity amongst the tubulin isotypes expressed in Physarum and suggests that monoclonal antibodies are valuable probes for individual members of multi-tubulin families. PMID- 4018261 TI - Conformational disorder of the distal leucine in monomeric Glycera hemoglobins and implications for oxygen binding. AB - 1H NMR studies of the carbon monoxide complexes of the major monomeric hemoglobins from Glycera dibranchiata show that distal leucine is conserved at position E7. The observed ring current shifts and nuclear Overhauser enhancements indicate conformational disorder of the leucine E7 side chain. The conformational substates interconvert rapidly on the NMR time scale. The rapid conformational fluctuations of leucine E7 may play a fundamental role in governing diffusion of ligands to the heme. PMID- 4018262 TI - Early transmembrane events in tumour cell responses observed by stopped-flow fluorometry. AB - Early transmembrane events of tumour cells (mouse myeloma X5563 and lymphoma RDM4) after binding of a monoclonal antibody against mouse MHC antigen and a mitogenic lectin, Con A, were examined by stopped-flow fluorometry with 3 different fluorescent probes. The results showed that membrane fluidities of the cells increased first after binding of anti H-2Kk monoclonal antibody (11-4.1), then calcium was released from intracellular stores into the cytoplasma, and lastly calcium influx occurred from the external medium into the cytoplasma. While Con A only induced calcium influx from the external medium into the cytoplasma. PMID- 4018263 TI - Polymerized liposomes as stable oxygen-carriers. AB - We have produced a surrogate erythrocyte ('hemosomes') by encapsulating human hemoglobin in polymerized vesicles composed of diacetylenic phospholipids plus or minus cholesterol. Hemoglobin (in the presence or absence of allosteric effectors) was encapsulated by a freeze-thaw method in large, unilamellar vesicles composed of monomeric lipids. Entrapment was demonstrated by molecular sieve chromatography. Brief irradiation with ultraviolet light produced polymeric hemosomes with polymerization kinetics and conversions similar to liposomes in the absence of protein. Photo-induced oxidation of the heme was eliminated or severely limited by a combination of prior ligation with CO and the maintenance of high intravesicular hemoglobin concentrations (5-10 mM internal hemoglobin). The inclusion of allosteric effectors within polymerized hemosomes facilitated near-quantitative conversion to the oxy-HbA form. Gas permeability of monomeric and polymeric hemosomes was demonstrated by spectroscopic methods. Reversible spectral shifts, corresponding to oxygenation-deoxygenation, were obtained after brief evacuation and exposure to oxygen or nitrogen. The gas permeability of polymerized hemosomes appears sufficient for the vesicles to act as oxygen carriers in vivo, a notion that is strengthened by their apparent hemocompatibility. PMID- 4018264 TI - Protein thiols in normal and neoplastic human uterine cervix. AB - Protein-thiol groups that react with dihydroxydinaphthyl disulphide during a 7 h incubation (so-called reactive protein thiols, PSHr) have been quantitatively measured on sections of human uterine cervix by microcytospectrophotometry. Measurements were made on areas (1 micron 2) of epithelium and adjoining stroma in samples of normal cervix, and in samples obtained from patients with dysplasia, carcinoma-in-situ and invasive cancer. The ratio of PSHr in epithelium to stroma is substantially reduced in the pathological conditions compared with normal and in apparently normal adjacent areas. Such changes in PSHr are discussed in relation to the redox balance of the tissue, and free radical disturbances previously described. PMID- 4018265 TI - Bile acid binding in plasma: the importance of lipoproteins. AB - Bile acid (BA) hydrophobicity, evaluated by the octanol-water partition coefficient, decreases along the series deoxycholic acid-chenodeoxy cholic acid hyodeoxycholic acid-ursodeoxycholic acid-cholic acid (CA)-ursocholic acid (UCA). In vitro experiments carried out using dialysis techniques (to determine the maximum BA binding) and ultrafiltration of plasma pre-incubated with 0.1 mM BA (to assess the distribution of BA between the different lipoprotein fractions) showed that the maximum binding of BA to plasma and lipoproteins follows the same order of hydrophobicity. The fraction not bound to proteins, greater with the hydrophilic BA (UCA and CA), is distributed in the lipoprotein fractions and in particular in high density lipoproteins. PMID- 4018266 TI - Limited proteolysis of pig liver CoA synthase: evidence for subunit identity. AB - The bifunctional enzyme CoA synthase can be nicked by trypsin without loss of its activities. The original dimer of subunit Mr approx. 61 000 yields fragments of Mr 41 000 and 22 000 as seen on gel electrophoresis in the presence of SDS, but the nicked enzyme retains the native Mr of 118 000. Further proteolysis occurs rapidly in the absence of protecting substrates. The N-terminal of native CoA synthase is proline, and proteolysis exposes glycine as a second N-terminal. This evidence strongly suggests that the subunits are identical. PMID- 4018267 TI - Protein fatty acyltransferase is located in the rough endoplasmic reticulum. AB - The fatty acid acylation of polypeptides was studied in vivo and in vitro by incorporation of radiolabeled palmitic acid into Semliki Forest viral polypeptides. Utilizing a cell-free system for acylation protein fatty acyltransferase was characterized as an integral membrane protein. No acylation activity was detected in the cytosol. During subcellular fractionation of a variety of mammalian or avian cells the enzyme was localized to the rough endoplasmic reticulum. Therefore this posttranslational hydrophobic modification starts earlier in the biosynthesis of acylated polypeptides than previously believed. PMID- 4018268 TI - Rat pancreas contains the proglucagon(64-69) fragment and arginine stimulates its release. AB - Rat proglucagon(64-69) corresponding to the C-terminal hexapeptide of putative rat glicentin sequence in the precursor was synthesized. A glicentin C-terminal hexapeptide specific radioimmunoassay, using the synthetic hexapeptide as standard, demonstrated the presence in rat pancreas of a peptide identified with the synthetic rat proglucagon(64-69): H-Asn-Arg-Asn-Asn-Ile-Ala-OH. The hexapeptide was released concomitantly with glucagon by arginine stimulation from the isolated perfused rat pancreas. The results indicate that the pancreas co stores and possibly co-releases the hexapeptide with glucagon as one of the processing products of proglucagon. PMID- 4018269 TI - Thioridazine: a selective inhibitor of peroxisomal beta-oxidation in vivo. AB - In vivo administration of the phenothiazine drug, thioridazine, inhibits hepatic peroxisomal beta-oxidation in mice. In starving animals, 3-hydroxybutyrate concentration is not decreased by thioridazine treatment. These results provide the first demonstration of thioridazine as a selective inhibitor of peroxisomal beta-oxidation in intact animals. Thioridazine might supply a tool for simulation of pathological conditions in which peroxisomal beta-oxidation is impaired. PMID- 4018270 TI - Footprinting of DNA secondary structure by high-intensity (laser) ultraviolet irradiation. AB - The action of high-intensity ultraviolet pulse laser radiation on a 161 bp fragment of pBR 322 DNA (EcoRI-MspI fragment) was studied. At doses up to 5 X 10(18) photons/cm2 the N-glycosidic bond splitting is negligible. The action of hot piperidine on irradiated DNA leads to chain splitting at the residues, modified via biphotonic processes. The modification and, hence, splitting efficiencies depend on the type of base (G greater than T greater than A greater than C) and on its position in the sequence. Preferentially modified bases in the opposite strands of double-stranded DNA belong, mainly, to the same or adjacent base pairs. Residues in the Pribnow box are modified considerably less, than in the sequences, immediately upstream and downstream. This approach seems to be useful in footprinting of DNA secondary structure peculiarities and alterations, conjugated with the functional role and state of the respective fragment. PMID- 4018271 TI - Preparation and amino acid sequence of human kappa-casein. AB - Human kappa-casein was prepared from whole casein by successive hydroxyapatite and thiol-Sepharose chromatographies. The primary structure of its 99-residue N terminal fragment has been determined by sequencing peptides obtained by tryptic and chymotryptic digestions of the whole protein. This fragment overlaps the known sequence of the 65-residue C-terminal fragment. The 158-residue sequence of human kappa-casein was compared to those of goat, ewe, cow and rat kappa-caseins. Only 22% of the residues are identical in homologous positions. The rate of divergence of the 93-residue N-terminal segment (para-kappa-casein) appears to be higher than that of the rest of the molecule. PMID- 4018272 TI - Oxyntomodulin (glucagon-37) and its C-terminal octapeptide inhibit gastric acid secretion. AB - Oxyntomodulin (OXM) is a peptide isolated from porcine intestine which consists of the whole glucagon sequence with a basic octapeptide (KA8) at its C-terminal end. In this study, the effect of OXM and KA8 on pentagastrin-stimulated gastric acid secretion has been studied in conscious rats and cats. In rats, OXM (25-450 pmol . kg-1) as well as KA8 (7.5-60 nmol . kg-1) inhibited pentagastrin stimulated gastric acid output in a dose-dependent manner; KA8 was about 100 times less potent than OXM. In cats, KA8 (90 nmol . kg-1) was also an inhibitor of acid secretion. We conclude that OXM, or a closely related peptide, could be a physiological modulator of gastric acid secretion, and that the C-terminal octapeptide of OXM is implicated in this effect. PMID- 4018273 TI - National Institutes of Health phase I, Small Business Innovation Research applications: fiscal year 1983 results. AB - A review of the 356 disapproved Small Business Innovation Research (SBIR) proposals submitted to the National Institutes of Health (NIH) for fiscal year 1983 funding was undertaken to identify the most common shortcomings of those disapproved applications. The shortcomings were divided into four general classes by using the scheme developed by other authors when describing the reasons for the disapproval of regular NIH research applications. Comparison of the reasons for disapproval of SBIR applications with regular applications suggests comparable difficulties in the areas of the problem and the approach. There is some indication, however, that the SBIR proposals may have been weaker in the category of the principal investigator (PI). In general, it is the responsibility of the PI to demonstrate that the work is timely and can be performed with available technology and expertise, and that the guidelines for the NIH SBIR program have been satisfied. PMID- 4018274 TI - Successful pregnancies from the transfer of pronucleate embryos in an outpatient in vitro fertilization program. AB - Twenty-nine infertile women were given clomiphene citrate (100 mg/day, days 3 to 7), human menopausal gonadotropin (150 IU/day, days 7 to 12 or 13), and human chorionic gonadotropin (2000 IU) for the induction of ovulation. Eggs were collected by laparoscopy and preincubated for 6 hours before being cultured with spermatozoa for fertilization. Approximately 16 to 18 hours after insemination, the eggs that showed two pronuclei were transferred to the patient's uterus. As confirmed by the ultrasonic appearance of a gestational sac, six women who received pronucleate embryos became pregnant, and three pregnancies resulted in normal full-term deliveries. These results confirm that, unlike requirements for most laboratory and farm animals, the requirements of synchrony between the preimplantation human uterus and developing embryos are not very stringent. In vitro fertilization treatment procedures can thus be made simpler by the transfer of embryos at the pronucleate stage. PMID- 4018276 TI - Increased maternal serum 3 alpha, 17 beta-androstanediol glucuronide concentrations during pregnancy. AB - Maternal serum concentrations of 3 alpha, 17 beta-androstanediol glucuronide (3 alpha-diol-G), a substance that reflects peripheral androgen action and tissue 5 alpha-reductase activity, were measured in 33 normal men, 51 nonpregnant women, and 51 women with uncomplicated pregnancies. The 3 alpha-diol-G concentrations in men (median, 201 ng/ml) were significantly higher than in nonpregnant women (median, 42 ng/ml) or pregnant women (median, 124 ng/ml). The concentrations in pregnant women were significantly greater than those in nonpregnant women, and there were no significant differences between trimesters in maternal 3 alpha-diol G concentrations. There were no fetal sex differences found in maternal serum or in third-trimester amniotic fluid. These results indicate that pregnancy is associated with increased androgen production by maternal tissues and that fetal 3 alpha-diol-G production is low. PMID- 4018275 TI - A new method for predicting and confirming ovulation. AB - Evaluation of a method for predicting and confirming ovulation by measurement of vaginal and salivary electrical resistance (VER and SER) was the purpose of this study. Eighteen menstrual cycles from 13 subjects were analyzed. A clearly defined nadir in VER at day 0, the day of the luteinizing hormone (LH) peak, followed by a pronounced increase the following day was observed. A peak in SER was consistently observed 5 to 6 days before day 0. The correlation coefficient (r) between the cycle day of the SER peak and cycle day of the LH peak was 0.94. After the peak in SER, values were low for several days but increased 1 to 2 days before the LH peak. Results indicate that monitoring of SER and VER may provide the basis for a simple method for predicting and confirming ovulation. PMID- 4018277 TI - Absence of chorionic gonadotropin in sera of women who use intrauterine devices. AB - A controlled study was undertaken to determine whether unnoticed pregnancies routinely occur in users of the intrauterine contraceptive device (IUD). Starting on day 10 of the menstrual cycle and continuing through the onset of menstruation or until the diagnosis of pregnancy, we collected daily blood samples from three groups of normally menstruating young women. The study groups were (A) IUD users (n = 30), (B) women with tubal ligation (n = 30), and (C) women trying to become pregnant (n = 15). The sequential serum samples were analyzed by radioimmunoassay for progesterone (P), human luteinizing hormone (hLH), and human chorionic gonadotropin (hCG). No positive hCG assays in luteal phase blood sera of IUD users were observed. The only positive hCG determinations of IUD users coincided with the preovulatory surge of hLH. Two subjects who became pregnant, as judged by progressive increases in hCG and P levels in the luteal phase, belonged to the group planning pregnancy. The finding of two pregnancies in 15 months of exposure is consistent with the assumption of natural fertility. The probability of no pregnancies in 30 months at risk, as observed among the IUD users, is between 1 in 200 and 1 in 100,000, depending on the assumption made for natural fertility. The study demonstrates that IUD users do not retain their natural fertility, and that IUDs do not exert their antifertility effect as abortifacient agents. If a confirmed pregnancy is detected in an IUD user, it may be assumed to represent an isolated case of contraceptive failure. PMID- 4018279 TI - Obstructing malformations of the uterus and vagina. AB - Sixteen cases of obstructing malformations of the uterus and vagina treated at The Children's Hospital between 1970 and 1983 are discussed. These patients typically present with pain within 2 years of their menarche and a pelvic mass. Unilateral renal agenesis is the most common associated nongynecologic defect encountered (53%). The key to early diagnosis is a high index of suspicion when significant gynecologic symptoms develop in perimenarchal patients. A complete investigation should be carried out before the undertaking of corrective surgery, because a thorough understanding of the patient's anatomy is necessary for the determination of the type of operation that will optimally preserve reproductive and sexual function. The specific abnormalities encountered in this series are divided into three groups on the basis of the site(s) of obstruction. Recommendations for surgical treatment of each group are presented. PMID- 4018278 TI - Recovery of Chlamydia trachomatis from the endometrium in infertile women with serum antichlamydial antibodies. AB - Upper genital tract infection with Chlamydia trachomatis appears to be a frequent cause of salpingitis and tubal infertility. However, the prevalence of active infection in women with infertility has not been well-defined. To examine this question, endocervical and endometrial cultures for C. trachomatis were obtained from infertile women with serum antibodies to C. trachomatis. The first 19 consecutive patients with titers greater than or equal to 1/32 were cultured. C. trachomatis was recovered from the endometrium or endocervix in six (32%) of the women examined and from the endometrium in five (26%). These findings indicate that a significant portion of infertile women with serum antichlamydial antibodies may have active upper genital tract infection with C. trachomatis at the time of presentation. PMID- 4018280 TI - Regret after decision to have a tubal sterilization. AB - To determine characteristics associated with regretting sterilization that can be determined preoperatively, we analyzed data from the Collaborative Review of Sterilization (CREST), a multicenter, prospective, observational study. Of 5022 women, 2.0% regretted having had a tubal sterilization at 1 year after the procedure and 2.7% did so after 2 years. Using a multivariate analysis to identify risk factors for regret, we found that almost all characteristics were more closely associated with regret at 1 year than at 2 years postoperatively. Of the characteristics we examined that could be objectively determined preoperatively, we considered only age less than 30 years and (for whites) a concurrent cesarean section to be risk factors for regret at 2 years after sterilization. However, in absolute terms, less than 10% of women with both those risk factors regretted having the procedure. PMID- 4018281 TI - Prolonged storage of human spermatozoa at room temperature or in a refrigerator. AB - Spermatozoa from patients who underwent in vitro fertilization (IVF) therapy were prepared free from seminal plasma with the use of IVF culture medium supplemented with 8% human serum. Samples were then stored either at room temperature or in a refrigerator, and their motility and ability to penetrate zona-free hamster eggs were assessed every second day. With storage at room temperature, motility declined by less than half over the first 14 days, with some samples still active 20 days after preparation. The ability of the samples to penetrate hamster eggs was unchanged during the first 6 days of storage, and most of the samples still had positive tests after 14 days. Some spermatozoa could still penetrate after 17 days. Room-temperature-stored spermatozoa were still able to fertilize human oocytes 5 days after preparation. With storage in a refrigerator motility declined rapidly, and few sperm were motile after 14 days. However, these samples penetrated relatively more hamster eggs after 14 days' storage than room temperature-stored samples did. Spermatozoa stored overnight in a refrigerator had significantly higher hamster egg penetration rates than spermatozoa stored overnight at room temperature. After storage overnight at room temperature, false positive and false-negative results of hamster egg penetration tests were common in relation to IVF outcome; after refrigerated storage, no false-negative results were found. PMID- 4018282 TI - An association between clomiphene citrate and ectopic pregnancy: a preliminary report. AB - Preliminary results of a case-control study suggest that CC or factors closely associated with CC therapy (or both) may increase the risk of ectopic pregnancy. It is hoped that these results will stimulate further research for more explicit evaluation of the role of CC and LPD in the etiology of ectopic pregnancy. PMID- 4018283 TI - Danazol in the management of ureteral obstruction secondary to endometriosis. AB - Ureteral obstruction caused by endometriosis is uncommon. It is, however, an important complication that imposes a 25% chance for permanent loss of renal function on the affected side. The standard management is surgical; however, three cases have been reported in which regression of obstruction followed medical therapy. This case report concerns a patient with long-standing partial ureteric obstruction due to endometriosis who was treated for 2 months with danazol. Clinical response of the endometriosis was excellent, but the obstruction persisted, a retroperitoneal ureteroneocystotomy was therefore performed. The ureter was found to be obstructed by dense fibrous tissue that contained endometrial glands. It seems therefore that a trial of danazol may be attempted in selected cases, but that the drug is unlikely to relieve endometriotic ureteric obstruction once dense fibrosis has occurred. PMID- 4018284 TI - The fetus is a graft, both biologically and legally. PMID- 4018285 TI - Cervical mucus determinations. PMID- 4018286 TI - Treatment of endometriosis with danazol. PMID- 4018287 TI - Exercise and oligomenorrhea. PMID- 4018288 TI - [Reaction of caudate nucleus neurons to acoustic stimulation during functional exclusion of the medial geniculate body]. AB - In chronic experiments, responses of the cat caudate nucleus neurons to sound clicks (0.2/s) were recorded extracellularly under conditions of functional blockade of the medial geniculate body (MGB). Analysis of the average poststimulus histograms showed that, under anodic polarization of the parvo- and magnocellular parts of the MGB, 39% of the caudate nucleus neurons responded to sound signals by a decrease of phasic activation and 30% of neurons--by its disappearance, 9%--by lengthening of latency of the responses. In some units the anodic polarization of the MGB magnocellular part induced an increase in phasic activation. Stimulation of the MGB exerted a facilitating effect on the unit responses of the caudate nucleus to clicks. PMID- 4018289 TI - [Effect of medullary chemosensitive structures on vascular neurogenic tonus]. AB - In anesthetized cats, blockade of the intermediate chemosensitive area (area "S") of the ventral medulla by means of local cooling to 20-22 degrees C induced drop of arterial blood pressure by 22% as well as of the perfusion pressure in hind limb skin-muscular and muscular preparations by 24% and 12%, resp. Analogous cooling of the caudal chemosensitive area (area "L") increased the BP by 6% as well as the perfusion pressure. Decentralizing of the hind-limbs prevented the perfusion pressure changes but did not affect the BP shifts. Raise of the temperature in the "S" area up to 41 degrees C increased both the BP and the perfusion pressure. Functional heterogeneity and role of the above chemosensitive areas in modulation of neurogenic vascular tone, are discussed. PMID- 4018290 TI - [1 possible triggering mechanism of regional redistributions of cardiac output in hypovolemia]. PMID- 4018291 TI - [Characteristics of baroreceptor reflexes as affected by negative and positive emotions]. AB - Changes of blood pressure (BP), intersystolic intervals (II), baroreflex sensitivity (BS) were studied during negative and positive emotions in unrestrained rats. Negative emotions induced raise of BP and reduced II and BS. The hemodynamic component of positive self-stimulation was due to its rewarding properties and not to direct effect of cerebral stimulation. It was characterized by BP elevation and II decrease, BS remaining unchanged. Hemodynamic manifestations of positive and negative emotions are discussed. PMID- 4018292 TI - [Changes in systemic and pulmonary hemodynamics during an increase in lung volume]. AB - 15 anesthetized dogs were subjected to a gradual increase of the lungs volume by means of administration of the 50% gas mixture of oxygen and air. The exceeding of the lungs volume by 600 ml increased pressure in the caudal vein, reduced blood flow and systolic pressure in the heart ventricles. After administration of 800 ml of the gas, the systolic pressure started to raise in the right ventricle and achieved 36.8 mm Hg at the moment of intrathoracic pressure of 21.5 mm H2O and cessation of the minor circulation. Then the right ventricle augmented its mechanic activity inducing tachycardia, raise of the pressure up to 45.2 mm Hg and restoration of the lung circulation. PMID- 4018293 TI - [Hyperemia in capillaries of the gastrocnemius muscle following stretching]. AB - Microcine-tv-study of the isolated m. gastrocnemius' capillaries in 9 anesthetized cats determined the blood flow mean velocity as 0.73 +/- 0.12 mm/s with a considerable dispersion for 216 capillaries (variation coefficient = 120 160%). The temporal dispersion of velocities in a single capillary was insignificant (variation coefficient about 45%). Longitudinal stretch of the muscle for 1-2 cm decelerated the capillary blood flow up to its complete arrest. After 1-min stretch, the blood flow velocity increased by 0.30 +/- 0.06 mm/s in 148 capillaries; decreased by 0.22 +/- 0.07 mm/s in 35 capillaries and remained the same in 5 capillaries. Apart from this, 4 capillaries initially invisible, became apparent. Average data for capillaries corresponded to those of macro experiments. Responses of individual capillaries seem to be unrelated to initial velocity of their location within the net, if only absolute values of velocities are to be analysed. PMID- 4018294 TI - [Mechanism of changes in central lymphatic volume flow with increase of pressure in the left atrium]. AB - In anesthetized adult dogs, stimulation of left atrium receptors caused an increase in the central lymph volume flow and a raise in transport capacity of the thoracic duct. Neither vagotomy nor blockade of muscarinic cholinergic fibers affected the reflex shifts in lymph volume flow or thoracic duct lumen. The efferent link of this reflex is represented by adrenergic nerve fibers. PMID- 4018295 TI - [Combined functioning of lymph-blood plasma systems in regulating lipid balance in dogs]. AB - Active participation of lymphatic system in the reconstruction of cholesterol pool during its passage from the intestinal lymph to the thoracic duct lymph was revealed. This phenomenon depends both on the directional dilution of intestinal lipids in the thoracic duct lymph and enzyme mechanisms of the maintenance of lipid balance occurring with the aid of lecithin-cholesterol-acyltransferase and lipoprotein lipase. The rate of transformation of the cholesterol pool correlates with the volume speed of thoracic duct flow. Walls of the intestine, lymphatic and circulatory systems seem to function within the framework of a single mechanism controlling the adequate status of circulatory lipids. PMID- 4018296 TI - [Interrelation of the morphofunctional characteristics of the erythron and heme synthesizing enzyme activity during heat exposure]. AB - A new erythrocyte population with increased cell diameter and volume appears during the adaptive readjustment of the erythron system with the augmentation of intracellular hemoglobin content in prolonged exposure to heat. The level of their hemosynthesizing enzymes activities correlates with different functional characteristics of erythron bone marrow shoot. PMID- 4018297 TI - [Effect of homeostasis of chyme composition on absorption of its components in the small intestine during natural digestion]. AB - In dogs, even after essential changes of food ingredients, chyme concentration indices, being formed in duodenum, are steadily kept over a comparatively small range of values in the aftermath of intensive exchange between blood and media filling the lumen of gastroduodenal area. The direction of the balance flow for each substance depends both on the substance initial concentration and the ingredients ratio of food. The homeostating of enteral medium seems to assure the relative stability of the substances balance flow filling up internal medium of the organism. PMID- 4018298 TI - [Electrical characteristics of the epithelial tissue and cells of the carp and frog gallbladder]. AB - Transepithelial potential and resistance, the ratio of resistance of the apical to the basal cell membranes (Ra/Rb) were studied during transmural current clamps in isolated frog and fish gall-bladder (GB) with Ringer's solution on both sides. The findings show that: 1) the difference between the mucosal and serosal membrane potentials (MPs) was 3-8 mV as determined by transmural potential; 2) the ratio Ra/Rb depends on the MP value: it was less than 1 if MP was about 30 mV, and more than 1 if MP was over 30 mV; 3) outward and inward current clamps (about 20 microA/0.3 cm2) produced linear changes of MP on both apical and basal membranes; at high currents (40-60 microA/0.3 cm2) linear dependence is distorted especially for apical membrane whose conductance abruptly increases during current clamps. PMID- 4018299 TI - [Activity of inferior colliculus neurons during lateralization of complex sounds]. PMID- 4018300 TI - [Analysis of the convulsive electrical activity in the basolateral nucleus of the amygdala]. PMID- 4018301 TI - [Relation of the frequencies of the rhythmic components of cortical and hippocampal electric activity to the intensity of stimulation of the reticular formation]. PMID- 4018302 TI - [Effect of hypoxia and hypoxic hypercapnia on hemodynamic indices and acid-base state of the blood in dogs]. PMID- 4018303 TI - [Television method for measuring the formed elements of the blood]. PMID- 4018304 TI - [Controllable amplifier for registering tissue blood flow by the hydrogen clearance method]. PMID- 4018305 TI - Hybridoma cultivation in defined serum-free media: growth-supporting substances. I. Transferrin. AB - Effect of transferrin and effect of transferrin omission on growth of hybridomas in serum-free medium were studied. Transferrin at concentration 0.5 microgram/ml and higher concentrations stimulated growth of hybridoma cells. The optimum growth-supporting concentration of transferrin was 5 micrograms/ml. Omission of transferrin led to death of hybridoma T3-03 cells within 3-4 days. Omission of transferrin for a period of only 24 h damaged cells so severely, that they were unable to recover fully. PMID- 4018306 TI - Alterations in CFU-GM growth in preleukaemic and leukaemic AKR/J mice. AB - The behaviour of committed CFU-GM bone marrow cells was investigated in leukaemic and preleukaemic AKR/J mice. The number of bone marrow CFU-GM decreased in the leukaemic stage of spontaneous AKR/J leukaemia. The addition of AKR/J leukaemic cells inhibited CFU-GM growth from normal target bone marrow. The bone marrow CFU GM growth was also reduced in late preleukaemic AKR/J mice, whereas no modification in the CFU-GM number in early preleukaemic animals was found. PMID- 4018307 TI - [A comparative study of the accelerated metabolism of cortisol, prednisolone and dexamethasone in patients under rifampicin therapy]. AB - Although rifampicin (RFP) is known to be one of the potent hepatic microsomal enzyme inducers, little has been reported about the detailed pharmacokinetics of glucocorticoids in patients under RFP therapy. In this paper, the metabolism of cortisol, prednisolone and dexamethasone were investigated comparatively by simultaneous injection of these glucocorticoids. Eleven patients under RFP therapy, including 7 with tuberculosis together with collagen diseases and 4 with tuberculosis alone, were studied. Sixteen normal volunteers and 4 patients with collagen diseases not under RFP therapy were also examined as controls. After 1 mg of betamethasone was administered orally on the previous night for the suppression of endogenous cortisol, a mixed solution of 1 mg each of cortisol, prednisolone and dexamethasone was given intravenously. Plasma steroid levels of periodically collected blood samples were determined by respective radioimmunoassay after extraction with dichloromethane and purification by paper chromatography. Half-times of plasma disappearance (t 1/2), metabolic clearance rates (MCR) and total apparent distribution volumes (V) of these glucocorticoids were calculated using the single compartment model. The mean values of t 1/2 of cortisol, prednisolone and dexamethasone in patients with collagen diseases under RFP therapy were 1.8 +/- 0.3 (Mean +/- SD) (p less than 0.05), 1.4 +/- 0.2 (p less than 0.001) and 1.3 +/- 0.3 hours (p less than 0.001), respectively, which were significantly shortened when compared with normal subjects (cortisol, 2.1 +/ 0.2; prednisolone, 2.5 +/- 0.7; dexamethasone, 3.5 +/- 1.0 hours). The MCR of cortisol, prednisolone and dexamethasone in these patients were 139 +/- 57, 141 +/- 53 (p less than 0.01) and 722 +/- 137 l/day/m2 (p less than 0.001), respectively, which were increased when compared with normal subjects (cortisol, 114 +/- 20; prednisolone, 75 +/- 25; dexamethasone, 153 +/- 45 l/day/m2). The metabolism of these glucocorticoids in patients with collagen diseases under RFP therapy were also accelerated when compared with those in patients with collagen diseases not under RFP therapy. The t 1/2 of cortisol, prednisolone and dexamethasone in patients with tuberculosis alone under RFP therapy were 1.3 +/- 0.3 (p less than 0.001), 1.4 +/- 0.5 (p less than 0.01) and 1.2 +/- 0.3 hours (p less than 0.001), respectively, which were significantly shortened when compared with normal subjects.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 4018308 TI - [The effects of progestogens on a human endometrial cancer cell line Ishikawa and a human breast cancer cell line MCF-7]. AB - The effects of Medroxyprogesterone acetate (MPA) and progesterone (P) on DNA and RNA contents of a human endometrial cancer cell line (Ishikawa) and a human breast cancer cell line (MCF-7) were studied using Flow cytometry. The results were as follows. MPA and P at a high dose of 10(-5) M inhibited their cell cycle progression through the G1 phase or G1-S phase boundary and showed a decrease in the number of cells which underwent DNA synthesis and mitosis. P at a low dose of 10(-7) M showed the lengthening of cell cycle time in the S phase. MPA at 10(-7) M had an inhibitory effect on the cell cycle progression of Ishikawa cells similar to that of a high dose of MPA whereas, in the case of MCF-7 cells, it showed a lengthening of duration in the S phase. Therefore, the dose responsibility of these cells to MPA were shown to be different. A high dose of MPA and P showed a decrease in the cytoplasmic and nuclear RNA contents. A low dose of MPA and P had no marked effect on the RNA contents. From these results, it was clarified that MPA, especially at a high dose, could substantially inhibit RNA synthesis and DNA synthesis with a delay of the cell cycle progression in hormone responsive cancer cells. PMID- 4018310 TI - [Met-enkephalin-Arg-Gly-Leu-like immunoreactivity-containing nerve fibers and cell bodies in the abdominal sympathetic ganglia of the rat--an immunohistochemical study]. AB - The occurrence and localization of Met-enkephalin-Arg-Gly-Leu (Met-Enk-Arg-Gly Leu)-like immunoreactivity in the lumbar paravertebral ganglion and the superior mesenteric ganglion in the rat were investigated by immunocytochemistry. Colchicine was employed as an axonal flow blocker to accumulate Met-Enk-Arg-Gly Leu in the nerve cell bodies. The Met-Enk-Arg-Gly-Leu serum (R 0171) was produced by immunizing a mixed breed female rabbit with synthetic Met-Enk-Arg-Gly-Leu conjugated to ascaris protein by the glutaraldehyde method. Sections, 7 micron in thickness, of Bouin-fixed and paraffin-embedded tissues were immunostained by the peroxidase-antiperoxidase (PAP) method. Results obtained were summarized as follows: Colchicine-untreated rats possessed no strongly-immunoreactive nerve cell bodies for Met-Enk-Arg-Gly-Leu in the lumbar paravertebral ganglion, though a few of them were weakly immunopositive. Met-Enk-Arg-Gly-Leu-like immunoreactivity showing nerve fibers were occasionally seen in nerve fiber bundles of the lumbar paravertebral ganglion. In the superior mesenteric ganglion, a dense network of positively immunostained nerve fibers with a beaded appearance were seen around nerve cell bodies which were immunonegative for Met Enk-Arg-Gly-Leu. In colchicine-treated rats, 55 percent of nerve cell bodies of the lumbar paravertebral ganglion showed various degrees of positive immunoreactivities for Met-Enk-Arg-Gly-Leu. Many strongly immunostained nerve terminals were seen in the lumbar paravertebral ganglion of colchicine-treated rats. In the superior mesenteric ganglion, the immunoreactivity for Met-Enk-Arg Gly-Leu in the beaded nerve fibers around nerve cell bodies was intensified by the colchicine treatment, whereas the nerve cell bodies themselves remained immunonegative for Met-Enk-Arg-Gly-Leu. PMID- 4018309 TI - [An epidemiological study of subacute thyroiditis in northern Japan]. AB - It is difficult to study subacute thyroiditis epidemiologically since it occurs sporadically and infrequently. Information about 1,127 cases (108 males, 1,019 females, from 1967 to 1982) of subacute thyroiditis in northern Japan was obtained through a questionnaire. It was found that the usual age for the disease was forty, that females predominated in a ratio of 10.6:1, and that the prevalent month was July. In clinical features, the frequencies of the inflammatory symptoms were high in the acute phase of the disease, and the frequencies of hyperthyroid symptoms increased with the progress of the disease. According to the course of the disease (days after the onset without treatment), the patients were divided into seven subgroups, such as 1 approximately 7 days, 8 approximately 14 days, 15 approximately 21 days, 22 approximately 28 days, 29 approximately 42 days, 43 approximately 56 days and over 57 days, respectively. Compared with the 1 approximately 7 days group, the erythrocyte sedimentation rate, serum T4 and T3 concentrations in the 15 approximately 21 days group showed a significant increase from 64 +/- 35 to 75 +/- 30 mm/h (p less than 0.001), 14.6 +/- 5.5 to 17.6 +/- 5.6 micrograms/100 ml (p less than 0.001) and 218 +/- 124 to 263 +/- 109 ng/100 ml (p less than 0.05), respectively, but the BMR showed as insignificant increase from 20 +/- 15 to 24 +/- 14%. The 24-hr 131I-thyroid uptake and resin sponge uptake (RSU) in the 21 approximately 28 days group were 1.2 +/- 1.5% and 35.1 +/- 6.7%, respectively; the former was significantly lower (p less than 0.02) and the latter was insignificantly higher than the values (2.0 +/- 2.6% and 33.9 +/- 7.9%, respectively) in the 1 approximately 7 days group. The recovery time in the steroid-treated group was 57.2 +/- 47.6 days, which showed a statistically insignificant difference from 64.8 +/- 50.5 days of the sodium salicylate-treated group. But the recovery time of 78.2 +/- 64.9 days in other anti-inflammatory drug-treated groups was significantly longer than that of the steroid and sodium salicylate-treated groups (p less than 0.001 and p less than 0.05). Among 9 viral diseases, such as measles, varicella, erythema infection, hand-foot and mouth disease, rubella, mumps, influenza, epidemic keratoconjunctivitis and acute hemorrhagic conjunctivitis observed in northern Japan and Miyagi prefecture in the past 4 years, mumps, hand-foot and mouth disease and epidemic keratoconjunctivitis were prevalent in summer.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 4018311 TI - Carcinogenic higher plant metabolites in the human diet in temperate countries: a review. AB - Interest has increased recently in the possible human carcinogenic effects of plant metabolites in the diet. Some psoralens, some pyrrolizidine alkaloids and 'bracken carcinogen' may be dietary carcinogens, the latter two via contamination of food products from animals ingesting toxic plants. With the exception of 'bracken carcinogen', the structures of these compounds have been established. Further research to quantify the levels of these compounds in foodstuffs and to correlate these with the amounts of the compounds having toxic effects in laboratory animals would be valuable. Epidemiological studies on critical-intake consumer groups would also be of value in defining the hazard, if any, the presence of these compounds in the diet poses to the consumer. PMID- 4018312 TI - The absence of rhamnose in human urine following the ingestion of gum karaya (Sterculia). AB - Urinary rhamnose estimations following ingestion of gum karaya were requested by the Scientific Committee for Food (EEC) in July 1983. Five male volunteers have therefore made 24-h urine collections prior to, and following, the ingestion of 10 g gum karaya for 15 days, an intake ten-fold greater than that approved in terms of the present temporary ADI (0-12 X 5 mg/kg b.w.). Paper chromatographic separations, with two solvent systems, were made on the fresh urine specimens and also after ten-fold enrichments of all urinary constituents. Standard aqueous solutions of rhamnose, and urine to which rhamnose had been added, showed the detection limit to be 0.2 microgram rhamnose. Independent examinations in two laboratories failed to detect rhamnose at this level in any of the urine specimens, Had 1% of the rhamnose present in 10 g gum karaya appeared in the 24-h urine specimens, it would have been detected. This confirms previous evidence that dietary gum karaya is neither digested nor degraded by enteric bacteria and is not absorbed to any significant extent in Man. PMID- 4018313 TI - Determination of synthetic growth promoters in bile. AB - To monitor the use of synthetic growth promoting hormones in red meat animals requires a sensitive and rapid method of analysis. This paper describes the development of such a method for these agents in bile, based on a high pressure liquid chromatographic purification procedure with detection and estimation by radioimmunoassay. PMID- 4018314 TI - A chemiluminescent immunoassay for 17 alpha-methyltestosterone. AB - An immunoassay for the xenobiotic anabolic compound methyltestosterone (MT) is presented. The detection is based on chemiluminescence of a MT-isoluminol conjugate. Applications are presented for detection of methyltestosterone and cross-reacting compounds in bovine urine and tissues of application sites isolated from slaughtered cattle, illegally treated with hormonal anabolics. PMID- 4018315 TI - Sulphiting agents in foods: some risk/benefit considerations. AB - The current toxicological status of sulphiting agents is reviewed, including evidence of adverse reactions to sulphited foods by a sub-population of asthmatics. Against this background are assessed the applications and benefits of sulphiting agents in foods. It is concluded that further information is required to determine the magnitude of risk and that, in the interim, the controlled use of sulphiting agents is justifiable. PMID- 4018316 TI - Ammonia caramels: specifications and analysis. AB - Twenty three UK commercially produced ammonia caramels and eight experimentally produced ammonia caramels have been analysed by a range of physical and chemical tests, which include solids content, nitrogen levels, colour intensity and pH. A statistical treatment of the results is reported. PMID- 4018317 TI - Interaction between plastics packaging materials and foodstuffs with different fat content and fat release properties. AB - The migration of an addictive (phenolic antioxidant) from different types of plastic food packaging materials (low density polyethylene [LDPE], high density polyethylene [HDPE], polypropylene [PP], acrylonitrile-butadiene-styrene [ABS] and high-impact polystyrene [SB]) into low-calorie (reduced fat) foodstuffs has been determined under normal storage conditions, and shown in most cases to be equivalent to migration into normal foodstuffs. Certain exceptions are discussed and related to the fat-release properties of the particular foodstuffs. Additive transfer into low-calorie products, as well as into emulsions of fat and water, has been compared with that into aqueous acetic acid and test fat HB 307 under normal storage conditions and after 10 days at 40 degrees C. The transfer of antioxidant from plastics was found to decrease in the order LDPE, HDPE, PP, SB and ABS. Migration was found to be higher into pure fat and margarine than into mayonnaise. When comparing absorption from different emulsions of fat and water, the ranking for plastics was the same as the above with LDPE having a greater absorption than HDPE, except that ABS and PP had absorptions of the same order whilst it was significantly higher for SB. The type of emulsion was, however, found to have a greater influence on migration of the antioxidant from the polymer than on the fat absorption from the emulsion. The results are discussed in relation to earlier work and also with respect to the classification of foodstuffs. PMID- 4018318 TI - Improved methodology for the simultaneous detection of the trichothecene mycotoxins deoxynivalenol and nivalenol in cereals. AB - A simple and sensitive method has been developed for the analysis of two trichothecene mycotoxins (deoxynivalenol and nivalenol) in cereals. These toxins were extracted with acetonitrile/water (3:1), defatted with n-hexane and purified by a two-step chromatographic procedure using Florisil and Sep-pak columns. The amounts of deoxynivalenol (DON) and nivalenol (NIV) in the column eluates were quantitated by gas chromatography with electron capture detector and gas chromatography-mass spectrometry (selected ion monitoring). The limits of detection of the method were 2.0 micrograms/kg for DON and NIV with recoveries of the toxins spiked into polished rice, wheat and corn at 300 micrograms/kg averaging 87% and 86% respectively. PMID- 4018319 TI - Chromium in foods and the diet. AB - Food is the main source of chromium intake by man. Chromium is fairly evenly distributed throughout the various food groups examined, but highest concentrations of chromium are found in the meat, fish, fruit and sugar groups. Mean dietary chromium intakes in the UK (1976-78) were between 80 and 107 micrograms/day. PMID- 4018320 TI - Naturally occurring oestrogens in foods--a review. AB - This review is concerned with the presence of naturally occurring oestrogens in food plants and processed foods. Particular emphasis is placed on isoflavones and coumestans, both of which are true plant oestrogens, and the resorcylic acid lactones, more correctly classified as fungal oestrogens. The metabolism and mode of action of these compounds is discussed and their biological potencies, determined in both in vivo and in vitro studies, described. Current methods of analysis are indicated and the levels of these oestrogens in food plants, processed foods and foodstuffs are presented. Botanical, environmental or technological factors affecting the possible intake of plant and fungal oestrogens are mentioned and the hazard associated with such intake is compared with that originating from other dietary or medicinal hormonally active substances. Indications are given of the wide range of common food plants which have been reported to possess oestrogenic (uterotropic) activity, although it is emphasized that in general further work is necessary to substantiate these claims and to confirm the identities of the biologically active principles which have in some cases been proposed. In the concluding section suggestions are made for additional research considered important or necessary in this interesting area. PMID- 4018321 TI - Mechanism and detection of osteoporosis. PMID- 4018322 TI - Preanesthetic and preoperative evaluation. PMID- 4018323 TI - The cephalosporins revisited. PMID- 4018324 TI - Intrinsic third ventricular craniopharyngioma: two case reports with review of the literature. PMID- 4018325 TI - [Avidity of single-stranded DNA antibodies and its importance for the pathogenesis of autoimmune diseases]. PMID- 4018326 TI - [Toxoplasma antibodies in Behcet's disease]. PMID- 4018327 TI - [Ultrastructural criteria in Kaposi's sarcoma]. PMID- 4018328 TI - [Caterpillar dermatitis caused by Thaumatopoea pinivora Treitschke]. PMID- 4018329 TI - [Folk medicine in Ethiopia. 1. Dermatological and health policy aspects]. PMID- 4018330 TI - [Therapeutic trial with isonicotinic acid hydrazide in chronic stationary psoriasis]. PMID- 4018331 TI - [Modification of skin surface film by tenside/lipid mixtures]. PMID- 4018332 TI - [Inverse type Sturge-Weber syndrome]. PMID- 4018334 TI - [Folk medicine in Ethiopia. 2. Tradition and the present]. PMID- 4018333 TI - [Effect of monochromatic UV irradiation on the viability of human lymphocytes]. PMID- 4018335 TI - [Gonorrhea and pustules of the hands]. AB - Two similar cases of disseminated infection by Neisseria gonorrhoeae were observed at the same time. The patients presented with fever, arthralgia, tenosynovitis, cutaneous pustules of the extremities. In one case, N. gonorrhoeae has been recovered from vaginal discharge; in the other, bacteriological investigations failed. From a review of the literature, it appears that: (1) acral vesiculo-pustular lesions and tenosynovitis represent the most suggestive signs of the disease; (2) it is obviously important to repeat the bacteriological investigations; (3) biological data, included serology, are useless. However, immunofluorescence techniques might detect altered germs in the skin. PMID- 4018336 TI - [Atypical measles]. AB - Atypical measles with high fever, pneumonitis, erythematous papular and pustular rash occurred in a 16-year-old girl who had been vaccinated with the inactivated (killed) virus 15 years ago. PMID- 4018337 TI - [Stewart-Treves syndrome]. AB - A Stewart-Treves angiosarcoma (Stewart-Treves syndrome) developed 14 years after mastectomy (Halsted) and radiotherapy for breast cancer in a woman now 56 years old. Limited excision, graft and complementary radiotherapy have controlled the disease for 20 months. The microscopical and ultrastructural features of this angiosarcoma are presented and the last advances in immunopathology briefly commented. PMID- 4018338 TI - [Basal cell nevus syndrome]. AB - A 90-year-old female presented with multiple nevoid basal cell epitheliomas, skeletal defects and jaw cysts. The syndrome is briefly revisited. PMID- 4018339 TI - [Superficial pemphigus during the treatment of rheumatoid polyarthritis with D penicillamine and piroxicam (Feldene)]. AB - The authors report a new case of induced pemphigus: a 64-year-old man has had rheumatoid arthritis for 10 years. When he developed his pemphigus, he had been taking D-penicillamine and piroxicam for about 8 months. He needed high doses of prednisolone associated with azathioprine to clear his eruption. The case had a fatal outcome. PMID- 4018340 TI - Chemotaxis of nurse shark leukocytes. AB - Studies were conducted to determine the ability of leukocytes from the nurse shark to migrate in an in vitro micropore filter chemotaxis assay and to determine optimal assay conditions and suitable attractants for such an assay. A migratory response was seen with several attractants: activated rat serum, activated shark plasma, and a pool of shark complement components. Only the response to activated rat serum was chemotactic, as determined by the checkerboard assay. PMID- 4018341 TI - In vitro degradation of endocytosed protein in pronephros cells of the char (Salmo alpinus L.). The effects of temperature and inhibitors. AB - In vitro degradation of 125I-formaldehyde treated human serum albumin (fHSA) in char (Salmo alpinus L.) pronephros cells was studied. The labelled protein was injected intravenously and after various intervals of time pronephros cells were isolated and degradation of internalized protein was measured. No degradation could be observed in cells isolated 30 min after injection. The degradation was very effective in cells isolated at later time points (60-90 min); as much as 65% of the initial cell associated labelled protein was degraded during 90 min incubation at 15 degrees C. The effect of temperature on degradation showed a linear course in the temperature range 0-20 degrees C when plotted in an Arrhenius plot. Monensin and ammonium ions inhibited degradation while colchicine had no effect when pronephros cells were isolated 75 min after the injection. PMID- 4018342 TI - Chemiluminescence by peripheral blood phagocytes from channel catfish: function of opsonin and temperature. AB - The ability of the peripheral blood phagocytes from channel catfish, Ictalurus punctatus, to produce chemiluminescence (CL) following ingestion of the enteric pathogen Edwardsiella ictaluri was evaluated under a variety of opsonic and temperature conditions. The CL response was influenced by the concentration of immune serum used to opsonize the bacteria as well as the presence of nonspecific, heat labile opsonins. Peak light emissions were diminished and the time to peak response was increased with a reduction in temperature. Temperature mediated changes in CL activity was accompanied by a corresponding change in intracellular killing. The addition of the metabolic inhibitors superoxide dismutase or sodium azide resulted in a reduction in CL and intracellular killing. PMID- 4018343 TI - Antibody diversity in fish. Isoelectrofocalisation study of individually-purified specific antibodies in three teleost fish species: tench, carp and goldfish. AB - Natural anti-DNP antibodies were isolated by affinity chromatography from individual sera of three Cyprinid fish species (carp, goldfish and tench) and their electrofocusing (IEF) spectra were analysed in reducing conditions. In addition, immune anti-penicillin and anti-BSA antibodies were isolated from individual and pooled tench sera, and studied by IEF techniques on reduced samples. Diversity rates appeared to be rather low in the three fish species, and striking similarities arose between individuals of a same species. These results can be interpreted by the existence of particular selective pressures operating in poikilothermic species as it was already suggested by Du Pasquier. No enhancement of antibody heterogeneity could be detected in the tetraploid (carp and goldfish) species. This result is also in accordance with the selection of a restricted germ-line determined antibody repertoire in lower vertebrates. PMID- 4018344 TI - The cobra complement system: II. The membrane attack complex. AB - Rabbit erythrocytes are lysed by cobra plasma. The membranes of the lysed rabbit erythrocytes exhibited typical ultrastructural complement lesions with an inner diameter of 72 A. Structures similar to human C5b-8 complexes were also visualized. The proteins found in membranes lysed by cobra plasma resembled closely the proteins of the human membrane attack complex in number and molecular weight. Cobra poly C9 that is resistant to reduction and boiling in SDS could also be demonstrated. These results indicate that the membrane attack complex of cobra complement is very similar to its mammalian counterpart. PMID- 4018346 TI - Transient killer cells mediating antibody-dependent cell cytotoxicity to chicken erythrocytes in mouse spleen during post natal development. AB - Anti CRBC-ADCC increased in spleens of C3H/He mice from 2 weeks after birth to a peak value at 7-9 weeks of age and then declined to at least 17 weeks. Spleen cells from 8 week-old mice were fractionated by Percoll discontinuous density gradients and Sephadex G-10 columns. At least two cell fractions mediating ADCC to CRBC targets have been identified. Percoll gradient separation revealed one cell fraction with monocyte and another with lymphocyte morphology. The spleen cells adherent to Sephadex G-10 columns were responsible for most ADCC and this fraction accounted for the majority of killer cells at 8 weeks of age. These adherent cells were responsible for most superoxide anion production when stimulated with opsonised zymosan. The ontogenetic pattern of Sephadex-adherent killer cells closely resembles that for natural killer (NK) cells. This is discussed with regard to the probable influx of monocyte-like cells in the spleen during the postnatal development of mice. PMID- 4018345 TI - Lymphocyte requirement for the functional development of follicle-associated epithelium. AB - Follicular development in the bursa of Fabricius was disrupted by testosterone treatment and chorioallantoic membrane grafting. Analysis by a quantitative histological technique demonstrated that testosterone treatment causes a dose dependent delay in development by inhibiting lymphoid proliferation. Inhibition of lymphoid development prevented the development of carbon transport ability by follicle associated epithelium. Reconstitution of follicular development by grafting treated bursae to the chorioallantoic membrane of untreated hosts results in the development of functional follicle associated epithelium. These results establish the lymphoid requirement for the development of transport ability by the follicle-associated epithelium. PMID- 4018348 TI - Microsurgery update 1982-1984. PMID- 4018347 TI - Simultaneous occurrence of fusion and nonfusion reaction in two colonies in contact of the compound ascidian, Botryllus primigenus. PMID- 4018349 TI - Report on surgical knives or back to the stone age! PMID- 4018350 TI - Hypermetropic and myopic keratokyphosis. PMID- 4018351 TI - Radial keratotomy. PMID- 4018352 TI - Argon laser trabeculoplasty in exfoliation glaucoma. A retrospective analysis. PMID- 4018354 TI - Technical modification in goniotomy using high viscous hyaluronic acid. PMID- 4018353 TI - Results of goniotrephination and of trabeculoplasty in open angle glaucoma. A preliminary report. PMID- 4018356 TI - Partial excision of the ciliary body in cases of severe secondary glaucoma. PMID- 4018355 TI - The glaucoma triple procedure. PMID- 4018357 TI - Closed microsurgery in the treatment of congenital cataracts. PMID- 4018358 TI - Surgery for Peters' anomaly. PMID- 4018359 TI - Cataract surgery following perforating injuries. PMID- 4018360 TI - Management of the posterior capsule. PMID- 4018361 TI - Complications of posterior chamber lenses. PMID- 4018362 TI - New aspects of pseudophakos fixation. PMID- 4018363 TI - Surgical revision of vitreous and iris-incarceration in persisting cystoid maculopathy (Hruby-Irvine-Gass-syndrome)--report on 27 eyes. PMID- 4018364 TI - Surgery of persistent hyperplastic primary vitreous. PMID- 4018365 TI - IOMSG microscope report 1984. PMID- 4018366 TI - Autonomic nervous dysfunction in severe pre-eclampsia. AB - We evaluated autonomic nervous function in 14 subjects with severe pre-eclampsia and 11 subjects with normal third-trimester pregnancies using standard cardiovascular tests, i.e. heart rate responses to deep breathing and standing up, and blood pressure response to standing up. Both of the heart rate responses were lower in subjects with severe pre-eclampsia than in the control group (P less than 0.01 and P less than 0.001, respectively). Four subjects with severe pre-eclampsia had postural hypotension, defined as a systolic blood pressure fall of at least 30 mmHg on standing. Our results show that severe pre-eclampsia may be associated with autonomic nervous dysfunction. The inability to regulate heart rate and blood pressure in response to postural alterations may compromise the placental and renal blood flow in certain conditions, emphasising the importance of bed rest in severe pre-eclampsia. PMID- 4018367 TI - The management of labor in high myopic patients. AB - The routine in our department for years used to be: prevention of bearing down during the end of the 2nd stage of labor in high myopic parturients, by forceps delivery, with the assumption that this will prevent increased intraocular pressure--thus preventing deterioration or increased damage to the eyes. The goal of this study was to challenge our theory and thus we decided to re-evaluate this approach. Various obstetrical data were recorded in 50 women with myopia from 4.5 to 15.0 diopters who were admitted in labor to our department. Fundus examination was performed in all of them before and after delivery. Various types of retinal degeneration and retinal breaks were observed in most of them at their arrival but no deterioration of these retinal defects was observed in any of the cases at the later examination. In view of our results, it is recommended to let high myopic patients deliver spontaneously. PMID- 4018368 TI - Primary leiomyosarcoma of the vagina. AB - A case of primary leiomyosarcoma of the vagina is described and discussed. The tumor recurred and the patient died 8.5 years after the diagnosis and primary treatment. This is the longest survival time reported in the literature for a primary vaginal leiomyosarcoma. PMID- 4018369 TI - Congenital afibrinogenemia and recurrent early abortion: a case report. AB - The role of the fibrinogen molecule in the maintenance of normal pregnancy is not yet well understood; however, several cases have been previously reported in which failure to complete normal pregnancy was associated with either hypofibrinogenemia, dysfibrinogenemia, or deficiency in factor XIII (fibrin stabilizing factor) which is important for the crosslinking of the fibrin. A case of congenital afibrinogenemia is described. The patient, a 22-yr-old woman, who suffered from a moderate hemorrhagic tendency associated with very low (less than 10 mg/dl) plasma fibrinogen levels, had three consecutive spontaneous abortions. In view of the previous cases reported, the question is raised whether patients with low or abnormal fibrinogen should be treated with plasma transfusions in order to maintain a normal pregnancy. PMID- 4018371 TI - Proceedings of the symposium, Monoclonal antibodies in gynecologic oncology. PMID- 4018370 TI - An acardiac acephalic monster. AB - A case of an acardiac acephalic monster is described, and the literature concerning the incidence, classification and etiology of acardia is reviewed. Acardia is a very rare congenital anomaly occurring in less than 1 in 34600 deliveries. The acardiac monster has been reported only in multiple, monochorionic pregnancies. This bizarre anomalous fetus is sustained in utero by parasitic anastomoses to the circulation of its usually normal co-twin and is therefore not compatible with extrauterine survival. Possibilities for prenatal diagnosis and complications during pregnancy and delivery are considered. PMID- 4018373 TI - Use of the CA 125 antigen in diagnosis and monitoring of ovarian carcinoma. PMID- 4018372 TI - Use of intermediate filament antibodies in the differential diagnosis of gynecological neoplasia. PMID- 4018374 TI - In vitro serum assay for breast cancer monitoring. PMID- 4018375 TI - Monoclonal antibodies in gynecological oncology: facts and future. PMID- 4018376 TI - Inverse ratio of hCG in peritoneal fluid to that in serum in normal and tubal pregnancies. AB - The ratio of hCG in peritoneal fluid (PF) to that in serum (S) was studied in 60 patients with normal pregnancies (5th-15th wk of gestation = control group) and in 12 tubal pregnancies, 7 tubal abortions (5th-10th wk of amenorrhea) and one case of an early interstitial pregnancy (8th wk). The PF level in the control group was in every patient lower than in S independent of the gestational age. The ratio PF to S ranged from 0.24 to 0.87 (mean +/- S.E.: 0.51 +/- 0.02). In contrast to this, the patients with tubal pregnancy and tubal abortion showed in each case higher PF levels than in S. The ratio in the group with tubal pregnancy ranged from 1.1 to 374 (54 +/- 30) and in the group with tubal abortion from 1.2 to 162 (33 +/- 23). The difference in the ratio between the control group and both tubal pregnancy and tubal abortion was highly significant (P less than 0.001). The ratio of PF to S in the patient with interstitial pregnancy (0.73) did not differ from the control group. At the time of investigation, the S levels in all but 2 patients with ectopic pregnancy were below the range for normal pregnancy of the same gestational age. These findings indicate that the hCG ratio of PF to S may be dependent on the location of the gestational product. PMID- 4018377 TI - Twin pregnancy: case reports illustrating variations in transfusion syndrome. AB - The twin transfusion syndrome is diagnosed in 5.5% to 14.6% of monochorionic twins and the classical picture reveals a small anemic donor and a large plethoric recipient. Many other clinical discrepancies have been described. Today, by ultrasound it is possible to diagnose the syndrome in (early) pregnancy. In these case reports different clinical pictures and the importance of ultrasound are described. In twin pregnancies repeated ultrasound examinations should be considered with the consequences of vascular anastomoses. PMID- 4018378 TI - Perinatal mortality in breech presentations as compared to vertex presentations in singleton pregnancies: an analysis based upon 57819 computer-registered pregnancies in The Netherlands. AB - In 1982, nationwide registration of obstetric data was instituted in The Netherlands with about 70% of all Dutch hospitals participating. The resultant data from 57819 singleton pregnancies in vertex or breech presentation at delivery was studied. The vertex and breech groups were compared. The proportion of breech presentations relative to vertex presentations was greater in low gestational age infants and those of low birthweight. After correction for gestational age and birthweight, the perinatal mortality was higher in the breech groups than in the vertex groups. Congenital malformations occurred more frequently in the breech group but, even after exclusion of infants with congenital malformations, perinatal mortality remained higher in the breech group at any gestational age. Caesarean section was more frequently performed in the breech group than in the vertex group but did not appear to improve the outcome of breech presentation. It is possible that breech presentation is not coincidental but is a consequence of poor fetal quality, in which case medical intervention is unlikely to reduce the perinatal mortality associated with breech presentation to the level associated with vertex presentation. PMID- 4018379 TI - Limited proteolysis of enzymes: the generation of functionally modified derivatives in vitro and in vivo. PMID- 4018380 TI - Control of ornithine decarboxylase in the cellular slime mould Dictyostelium discoideum. PMID- 4018381 TI - Bacterial polyamines, structures and biosynthesis. PMID- 4018382 TI - Polyamine metabolism in mammalian cells in culture. PMID- 4018383 TI - The identification and characterization of a polyamine-accumulation system in the lung. PMID- 4018384 TI - The application of some newer aspects of immunoassay to clinical endocrinology. PMID- 4018385 TI - Cellulose hydrolysis: the potential, the problems and relevant research at Galway. PMID- 4018386 TI - Properties of cellulolytic enzyme systems. PMID- 4018387 TI - Regulation of cellulase biosynthesis and secretion in fungi. PMID- 4018388 TI - Rat brain differentiation antigens. PMID- 4018389 TI - Kynurenine hydroxylase: a potential rate-limiting enzyme in tryptophan metabolism. PMID- 4018390 TI - Flavin-dependent hydroxylases. PMID- 4018391 TI - Factors affecting the oral absorption of esterified antibiotics. PMID- 4018392 TI - The use of controlled-release glass for the controlled delivery of bioactive materials. AB - CRG can provide a useful supplement to other methods of controlled delivery. Some advantages of this approach are: The constituents of the CRG can be limited to biologically safe ionic species such as Na+, Ca2+ and PO4(3-). The release system is completely soluble in water and no residue remains. There is no evidence of any mechanism for biodegradation of the CRG and so one possible cause of premature or accelerated release is eliminated. The absolute release rate can be selected anywhere in a spectrum covering several orders of magnitude and the rate controlling process has zero-order kinetics. The release rate can be selected to be pH-sensitive or pH-independent. Complex temporal release-rate patterns can be obtained readily by the choice of geometrical shape or composition profile of the device. The controlled release of organics or other heat-sensitive materials which cannot be incorporated in the glass can be realized by the use of composite structures in which the CRG is the rate-controlling constituent. A number of different functions can be performed by a single CRG-based device. For example, CRG can be used as a biomedical resorbable material in surgery and the CRG structural component can release an AM as it dissolves. Similarly the CRG of the sinter-composite used for organic AM release can itself release any selected inorganic adjuvant. CRG boluses containing either copper or cobalt and weighing approx. either 70 g or 15 g, have been administered to both cattle and sheep. More than 90% of the boluses remained either in the reticulum of trace element remained after dosing.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4018393 TI - Iodine content and density of thyroglobulin investigated by isopycnic centrifugation. AB - The density of in vitro iodinated thyroglobulin (Tgb) molecules, measured by isopycnic centrifugation, increases linearly with their iodine content. In contrast, the iodine to density (I:D) regression for differently iodinated native rat Tgbs is not constant but varies, depending on experimental conditions: For LID-fed rats the slope of the individual I:D regression line of each Tgb decreases linearly with the decreasing mean degree of iodination of the sample (r = 0.9104, P less than 0.01). On the other hand, in Tgb samples synthesized by propylthiouracil-blocked glands, the I:D regression is no longer linear. Rather, a bimodal pattern is obtained revealing a preexisting highly iodinated Tgb pool together with newly synthesized, non-iodinated protein. The results indicate: (a) the mean degree of iodination of a native Tgb cannot be estimated accurately if only its mean density is known, and (b) the degree of heterogeneity of iodination is identical for any in vivo produced Tgb sample with the same iodine content. PMID- 4018394 TI - Evidence for the specific binding of growth hormone to a receptor-like protein in rabbit serum. AB - The binding in vitro of 125I-human or bovine growth hormone (GH) to normal female rabbit serum has been studied using gel filtration to separate bound and free hormone. On Ultrogel AcA34 columns, a substantial peak of specific 125I-GH binding was observed at a MW approximately 120 000. This peak was not precipitable by 12.5% polyethylene glycol, a method used widely for solubilized hormone receptors. Assuming a 1:1 binding stoichiometry between GH (MW 21 000) and the binding protein, the MW of the binding protein would be approximately 100 000. Gel filtration of serum alone, followed by assessment of 125I-hGH binding in column fractions, indicated the binding protein had a similar MW (83 000-107 000). Specific binding of 125I-hGH was dependent on incubation time (equilibrium being reached in 2 h at 21 degrees C), Ca2+ concentration (0.5-2.0 mM) and serum concentration (a 1:5 dilution of serum giving 45.2 +/- 1.7% specific binding; mean +/- SE, n = 10). Binding was completely reversible (t 1/2 approximately 1.5 h) and specific for somatotrophic but not lactogenic hormones. Scatchard analysis revealed linear plots with a Ka 1.59 +/- 0.11 X 10(9) M-1 and capacity 3700 fmol/ml serum. The presence in rabbit serum of a high affinity, GH-specific, binding protein raises important questions regarding its identity and possible physiological role in modulating the delivery and/or activity of GH in vivo. PMID- 4018395 TI - Thyroxine-induced changes in rat liver mitochondrial cytochromes. AB - The effects of 10 days of thyroxine injection (15 micrograms/100 g body weight) on rat liver mitochondrial cytochrome concentration and on the percent reduction of the individual cytochromes during succinate-driven state III and IV respiration was spectrophotometrically determined at cytochrome-specific wave length pairs. The concentrations of cytochromes b, c, total c (c + c1) and a a3 increased in hyperthyroid rats. The concentration of cytochrome c1 remained constant in euthyroid and hyperthyroid rats. Changes in the concentration of the membrane-bound cytochromes were also determined by difference spectra in cytochrome c-depleted mitochondrial membranes. Cytochromes b and a a3 showed increased concentrations in hyperthyroid rats while the concentration of cytochrome c1 remained unchanged. Hyperthyroid mitochondria showed increased reduction of cytochromes b, c1, c and total c during state III respiration and cytochromes c1, c, and total c during state IV respiration. The percent reduction of cytochrome b decreased during state IV respiration in the hyperthyroid mitochondria. These results suggest that the increase in respiration observed in the hyperthyroid state may be related to changes both in the mitochondrial cytochrome concentration and in the cytochrome reduction level. PMID- 4018396 TI - Weak androgen reduces the rate constant of beta-glucuronidase induction. AB - Administration of androgen to mice induces kidney beta-glucuronidase. Measuring beta-glucuronidase activity, rate of beta-glucuronidase synthesis, beta glucuronidase mRNA activity and beta-glucuronidase mRNA concentration, the time course of induction was compared using a strong androgen, dihydrotestosterone (DHT), and a weakly androgenic progestin, medroxyprogesterone acetate (MPA). Using MPA resulted in a longer lag, a 3-4-fold slower rate of induction as defined by the forward rate constant, ka, a lower final extent of induction, and a slightly lower turnover constant, kb. Differences in kinetics of induction were consistent for all 4 measured parameters, and mimicked previously described genetic differences in these rate constants. The coordinate induction of beta glucuronidase protein and beta-glucuronidase mRNA indicates that the response to androgen is regulated at a pre-translational level. That substitution of MPA for DHT decreases ka, rather than increasing kb, suggests that induction of beta glucuronidase follows an increased rate of mRNA synthesis rather than a decreased rate of mRNA turnover. Finally, the results are consistent with a model in which the kinetic constants for beta-glucuronidase induction are dependent on the concentration of receptor molecules in the active conformational state. PMID- 4018398 TI - Identification of specific binding sites for acetylated low density lipoprotein in microvillous membranes from human placenta. AB - The ability of microvillous membranes isolated from human placenta to specifically bind human low density lipoprotein (LDL) modified by acetic anhydride has been investigated. The presence of saturable high affinity binding sites specific for [125I]acetyl-LDL was demonstrated. Scatchard analysis of the binding data, obtained at 4 degrees C, revealed a single class of sites with a mean KD value of 3.63 +/- 1.16 micrograms acetyl-LDL protein/ml, and a maximal binding capacity of 335.1 +/- 148.8 ng acetyl-LDL protein/mg of membrane protein. At 37 degrees C, the binding capacity was increased, while the KD value was not modified. The specificity of these binding sites was assessed by competition studies: unlabelled acetyl-LDL were effective competitors, whereas native LDL, VLDL and HDL3 were ineffective. Conversely, unlabelled acetyl-LDL failed to prevent the binding of native [125I]LDL to placental microvilli. The [125I]acetyl LDL binding was partially inhibited (about 35%) by dextran sulfate and fucoidin, and was abolished by a pretreatment of the microvillous membranes with pronase. The binding sites specific for acetyl-LDL are present during all the gestation and are distinctly different from the binding sites for native LDL, previously characterized in placental microvilli. These 2 types of binding sites may be related to the high amount of cholesterol required by the human placenta for progesterone synthesis and trophoblastic growth. PMID- 4018397 TI - Relation between thyroid peroxidase, H2O2 generating system and NADPH-dependent reductase activities in thyroid particulate fractions. AB - In thyroid gland, iodination takes place on the apical plasma membrane and requires the presence of the thyroid peroxidase and H2O2 generating system. H2O2 generation and NBT (nitro blue tetrazolium) reductase activity (both of which are NADPH-dependent) as well as peroxidase activity were compared for their respective orientations in membrane vesicles. The possible role of NADPH-NBT reductase activity in H2O2 generation was also examined. Results favor the conclusion that thyroid peroxidase is oriented towards the luminal side of the vesicles, whereas the NADPH site of NADPH oxidase-dependent H2O2 generation is located on the external side of the same or of different vesicles. Furthermore, it is shown that different NADPH-NBT reductase activities are present on both the outer and inner surfaces of the membrane vesicles, and that none of these activities is able to produce either H2O2 or O-2. The idea that a multi-component complex is involved in H2O2 generation is discussed, and a model is proposed which takes into account the possible spatial separation of the thyroid peroxidase site from the NADPH site of this H2O2 generation system on the apical membrane of the thyrocyte. PMID- 4018399 TI - Isolation and characterization of osteogenic cells derived from first bone of the embryonic tibia. AB - Osteogenesis in the embryonic long bone rudiment occurs initially within an outer periosteal membrane and subsequently inside the cartilaginous core as a consequence of the endochondral ossification process. In order to investigate the development of these two different mechanisms of bone formation, embryonic chick tibial cell isolates were prepared from sites of first periosteal bone formation and from the immediately underlying hypertrophic cartilaginous core region. Mid diaphyseal periosteal collars and the corresponding cartilage core were microdissected free from Hamburger-Hamilton stage 35 (Day 9) chick tibias and separately digested with a trypsin-collagenase enzyme mixture. The released cell populations were cultivated in vitro and characterized by morphological analysis, histochemical localization of alkaline phosphatase, alizarin red S staining for mineral deposition, growth rate [( 3H]thymidine uptake), and proteoglycan content. Results of these studies showed that periosteal collar cell cultures form nodule-like structures that stain positive with alkaline phosphatase and alizarin red S. Light and electron microscopic observation revealed cell and matrix morphologies similar to that of intact periosteum. The nodules were composed of plump cell types embedded within a mineralized matrix surrounded by a fibroblastic cell layer. Core cartilage cell cultures displayed typical characteristics of the hypertrophic state in their visual appearance and proteoglycan composition. The formation of osseous-like structures in periosteal collar cell cultures but not in core chondrocyte cell cultures demonstrates the relatively autonomous nature of intramembranous ossification while emphasizing the dependence of the endochondral ossification process upon an intact vascularized environment present in the developing tibia. PMID- 4018400 TI - Growth regulation of the interstitial cell population in hydra. I. Evidence for global control by nerve cells in the head. AB - The interstitial cells of hydra form a multipotent stem cell system, producing terminally differentiated nerve cells and nematocytes during asexual growth. Under well-fed conditions the interstitial cell population doubles in size every 4 days. We have investigated the possible role of nerve cells in regulating this behavior. Nerve cells are normally found in highest concentrations in the head region of hydra, while interstitial cells are primarily located in the body column. Our experimental approach was to construct, by grafting, animals in which the density of nerve cells varied in (1) the head region, or (2) the body column. The growth of the interstitial cell population was then measured in these hydra. The results indicate that differences in head nerve cell density are closely correlated with how fast the interstitial cell population increases in size. Variations in the level of either nerve cells or interstitial cells in the body column showed no such correlation. These findings suggest the existence of a signaling mechanism in the head region. This signal, which is a function of the density of head nerve cells, emanates from the head tissue and exerts global control on the growth of the interstitial cell population in the body column. PMID- 4018401 TI - Spermatogenesis in Hydra oligactis. I. Morphological description and characterization using a monoclonal antibody specific for cells of the spermatogenic pathway. AB - A morphological description of cells participating in sperm formation in Hydra oligactis males using a maceration procedure is presented. These descriptions are corroborated by the use of a monoclonal antibody, AC2, that binds to both a subpopulation of interstitial cells that appears to participate exclusively in gamete formation, and to all the gamete-differentiation products, including sperm intermediate cells, spermatids, and sperm. Use of the antibody as an interstitial cell marker has allowed an analysis of the behavior of the gamete-precursor (AC2+) subpopulation of interstitial cells during the asexual state and the early stages of gamete formation, when no differentiating sperm intermediates are present. The results indicate there is a gamete-producing subpopulation of interstitial cells which is present in low numbers in asexual males and undergoes extensive growth following the onset of spermatogenesis to give rise to sperm intermediate cells, and, eventually, the sperm. No input from the AC2- interstitial cells is required to account for this growth or subsequent sperm production. We speculate that the AC2+ interstitial cells may represent a unique subpopulation which is developmentally restricted to sperm production. PMID- 4018402 TI - Gametic and pleiotropic defects in mouse fetuses with Hertwig's macrocytic anemia. AB - Pleiotropic effects on germ cell number, hematologic status, and body size are described in 12- to 15-day WBB6F1 normal (+/-) and defective (an/an) mouse fetuses, with special emphasis on gametogenesis. Differences between genotypes were apparent by Day 12. At 12 days, normal testes contained many germ cells and frequent normal mitoses, and the number of germ cells increased rapidly from Day 12 to Day 15. By contrast, 12-day an/an testes contained fewer germ cells, frequently degenerating, and many abnormal mitoses. Their number of germ cells decreased rapidly, so that almost none persisted to Day 15. Normal ovaries contained many germ cells, with much normal mitosis on Day 12 and 13, followed by meioses, but the smaller an/an ovaries contained few germ cells, with little mitosis, some meiosis, and very much degeneration. The erythrocyte counts of both normal and anemic fetuses increased approximately fourfold between 12 and 15 days, but at comparable ages, total counts were always lower in an/an fetuses than in normal littermates. At all ages, Hertwig's anemic (an/an) fetuses were somewhat smaller than their normal littermates. Although both W/Wv and Sl/Sld mice also show macrocytic anemia and germ cell failure, the great difference in etiology of their germ cell defects indicates that an/an gene action must be qualitatively different from that in either W/Wv or Sl/Sld mice. PMID- 4018403 TI - Specific cellular expression of monoamine oxidase B during early stages of quail embryogenesis. AB - Monoamine oxidase-B (MAO-B) is one of two distinct molecular forms of MAO that in part regulate the cellular levels of biogenic amines. In order to determine whether discrete cell populations known to express aminergic properties in the vertebrate embryo also express MAO-B, the distribution of MAO-B-immunoreactive cells was examined in early developing quail embryos. Two major patterns of staining emerge. First, tissues known to express several aminergic characteristics are initially MAO-B positive at early stages of development and continue to express immunoreactivity through Zacchei stage 20, the oldest stage examined. These include cells of the sympathetic and some cranial and trunk sensory ganglia (beginning at stage 13), the pancreas (stage 14), and the brain stem raphe (stage 14). Second, other structures that contain or accumulate biogenic amines are transiently MAO-B immunopositive during early stages of development. These tissues include extraembryonic yolk sac and presumptive gut endoderm (with most intense staining between stages 8 and 13), the ventral trunk neural tube (stages 14 and 16), and the notochord (stages 8-10). MAO-B immunoreactivity disappears from these regions at different stages, and none are MAO-B positive by stage 19-20. Other structures without known aminergic properties during early development also stain; these include liver (stage 20), mesenchymal cells that surround the Wolffian duct and lung buds (stages 14 and 18), and endothelial cells surrounding the dorsal aorta (stages 14 and 20). In general, however, MAO-B appears to be distributed in embryonic tissues that can use this enzyme to regulate biogenic amine levels either transiently or during initial phenotypic expression of aminergic traits. PMID- 4018404 TI - Increased endocytosis of acetylcholine receptors by dystrophic mouse myotubes in vitro. AB - Multinucleated myotubes, grown in vitro from satellite cells of dystrophic mice (C57BL/6J/dydy) exhibit a reduced sensitivity to ACh. This reduction correlates with a reduced density of 125I-alpha-bungarotoxin (125I-BTX) binding sites on the surface of dystrophic myotubes. Denervated adult muscle fibers from dystrophic mice respond to Ach similarly to denervated normal muscle fibers. Furthermore, cultured dystrophic myotubes, treated with a brain extract which induces AChR clusterization, still show an impaired response to ACh and reduced 125I-BTX binding. Thus AChR function appears altered in dystrophic muscle cells in culture while it appears normal in dystrophic adult muscle, regardless of whether the receptors are dispersed on the membrane or clustered at the junctional site. Metabolic studies on the reduced AChR level in dystrophic myotubes revealed a dramatically reduced half-life (2 vs 10 hr) while the rate of synthesis was unchanged. An increased rate of internalization of AChR was observed in dystrophic myotubes with a corresponding relative increase of the "hidden AChR pool," which could be partially reduced by agents which disrupt the cytoskeleton. No structural alterations could be detected on the AChR molecule as its sedimentation coefficient and subunit composition appeared identical between normal and dystrophic myotubes. Thus the increased turnover of AChR in dystrophic myotubes either reflects subtle alterations of the molecule or a more generalized increase of endocytosis in this form of myopathy. PMID- 4018405 TI - Nerve growth factor-independent development of embryonic mouse sympathetic neurons in dissociated cell culture. AB - Although ganglia from neonatal mouse sympathetic ganglia require nerve growth factor (NGF) for survival in culture, explanted sympathetic ganglia from early embryonic stages do not require added NGF for survival and growth. To determine whether the change in growth factor requirement is due to changes in the neurons themselves, to variations in neuronal populations, or to changes in nonneuronal cells, we examined the response to growth factors by dissociated sympathetic neurons at various stages of development. Results indicate that neurons from the 14-day gestational (E14) superior cervical ganglion (SCG) do not require NGF for initial survival and neurite extension, but do require the conditioned medium neurite extension factor, CMF. By 2 to 3 days thereafter, whether in vivo or in culture, most neurons have developed a requirement for NGF for survival in culture. During the same period, there is a concomitant increase in responsiveness to NGF alone as a trophic agent. Changes in response to NGF are not due to changes in NGF content of ganglia, to interactions in culture with nonneuronal cells, or to age-related differences in NGF requirements for maximum survival. The changes in growth factor requirements may be related to mechanisms regulating specificity of nerve-target connections. PMID- 4018406 TI - Mapping of the early neural primordium in quail-chick chimeras. I. Developmental relationships between placodes, facial ectoderm, and prosencephalon. AB - Defined fragments of the anterolateral neural ridge and of the associated region of the neural plate of presomitic to three-somite stage quail embryos were grafted isotopically and isochronically into chick hosts. This resulted in the development of apparently normal brain and facial structures to which the contribution of the grafted tissue could be observed by means of the quail nuclear marker. It was shown that the anterolateral neural ridge contains the progenitor cells of the adenohypophyseal and olfactory placodes and also of the superficial ectoderm lining the nasal cavity and conchae and the superficial ectoderm of the beak. When the appropriate region of the neural ridge was involved in the quail-chick substitution, the egg tooth was made up of graft derived cells. Grafting of the neural plate area adjacent to the "ridge" territory containing the placodal ectoderm revealed that the presumptive region of the hypothalamus is in contiguity with that of the adenohypophyseal placode. The same observation was made for the olfactory placode and the floor of the telencephalon from which the olfactive bulb later develops. PMID- 4018407 TI - Cell lineage analysis in ascidian embryos by intracellular injection of a tracer enzyme. II. The 16- and 32-cell stages. AB - Cell lineages during development of ascidian embryos were analyzed by injecting horseradish peroxidase as a tracer enzyme into identified cells of the 16-cell and 32-cell stage embryos of Halocynthia roretzi. Most of the blastomeres of these embryos developed more kinds of tissues than have hitherto been reported, and therefore, the developmental fates of each blastomere are more complex. It has been thought that every blastomere of the 64-cell stage ascidian embryo gives rise to only one kind of tissues, but the finding that the several blastomeres at the 32-cell stage developed into at least three different kinds of tissues, clearly indicates that the stage at which the fates of every blastomere are determined to one tissue is later than the 64-cell stage. The results also clearly demonstrate that muscle cells are derived not only from B-line cells (B5.1, B5.2, B6.3, and B6.4) but also from A-line cells (A5.2 and A6.4) and b line cells (b5.3 and b6.5). Based on the present analysis as well as other studies, complete cell lineages of muscle cells up to their terminal differentiation have been proposed. In addition, lineages of nervous system, notochord, and epidermis are also discussed. PMID- 4018408 TI - Development of electrical rhythmic activity in early embryonic cultured chick double-heart monitored optically with a voltage-sensitive dye. AB - Double-hearted embryos were produced by whole-embryo culture of chick embryos which were microsurgically cut through the tissue of the anterior intestinal portal at the 1- to 6-somite developmental stage, at the time when the cardiac primordia have not yet fused in the bulboventricular region. The cultured embryos were removed from an incubator usually at the 7- to 10-somite stages of development, and then spontaneous electrical action potentials and/or contractions were optically recorded simultaneously from both the right and left half-hearts, using a 10 X 10- element photodiode matrix array together with a voltage-sensitive merocyanine-rhodanine dye (NK 2761). At the 7- to 8-somite stages, spontaneous action potentials were detected from bilateral prebeating half-hearts or sometimes from one half-heart. In each half-heart, the first spontaneous beating was often observed in the half-heart of the 9 somite embryos. In the beating half-hearts regular activity was always observed, while in the prebeating half-hearts at the 7- to 8-somite stages, both the regular and irregular rhythms of action potentials were detected, and the incidence of occurrence of regular activity significantly outnumbered that of the irregular rhythm. The heart rate in the left half-heart was faster than that in the right half-heart in the great majority of the prebeating and beating double-hearted embryos. PMID- 4018409 TI - Analysis of the origins and early fates of neural crest cells in caudal regions of avian embryos. AB - Holmdahl divided vertebrate embryogenesis into two phases called primary and secondary body development. Three primary germ layers are delineated during primary body development and undergo morphogenesis to form primary organ rudiments. In contrast, during secondary body development, the tail bud (a mesenchymal mass of cells located at the caudal end of the embryo and derived principally from Hensen's node) directly forms secondary organ rudiments. We have been testing Holmdahl's concept of primary and secondary body development by mapping the embryonic structures that originate from the tail bud. In the present study, we examined the origins of neural crest cells in caudal regions of avian embryos and observed two populations: primary neural crest cells derived from ectoderm and secondary neural crest cells derived from tail bud. Both types of neural crest cells originate locally, and little or no displacement of these cells occurs along the longitudinal axis. Some secondary neural crest cells seem to colonize the surface epithelium, forming a mosaic derived from both ectoderm and tail bud. Other secondary neural crest cells form spinal ganglia, differentiating as sensory neurons, satellite cells, and Schwann cells. Despite their strikingly different origins and locations, primary and secondary neural crest cells give rise to similar structures. PMID- 4018410 TI - Major protein changes during vitellogenesis and maturation of Fundulus oocytes. AB - The protein content of various size follicles was measured in Fundulus heteroclitus and indicated four phases of increase relative to follicle volume: Phases I (previtellogenic; estimated to be less than 0.01 mg/mm3), II (vitellogenic; 0.20 mg/mm3), III (early maturation; 0.03 mg/mm3), and IV (late maturation; 0 mg/mm3). A pronounced and rapid size increase occurs during maturation due to hydration, but protein uptake, which was also documented cytologically, contributes to about 16% of the volume increment during early maturation. Protein incorporation appears to stop abruptly at the time of germinal vesicle breakdown, most likely reflecting an altered physiological state of the oocyte. SDS-polacrylamide gel electrophoretic patterns of various size follicles indicated that five major protein bands (molecular weights = 122, 103, 45, 26, and 20 k) accumulate during vitellogenesis and presumably are proteolytically derived from a 200-kDa vitellogenin precursor. During maturation, the 122- and 45-kDa proteins disappear and several new, lower molecular weight bands appear. Proteolysis of specific yolk proteins may thus help generate part of the osmotic pressure gradient required for water uptake during oocyte maturation. PMID- 4018411 TI - Differential participation of ventral and dorsolateral mesoderms in the hemopoiesis of Xenopus, as revealed in diploid-triploid or interspecific chimeras. AB - The thymocytes in the early larvae of Xenopus laevis have been shown to be derived from precursor cells immigrating interstitially through the mesenchyme into the organ rudiments at 3-4 days of age (Nieuwkoop and Faber stages 42-45). Orthotopic grafting of diploid tissues onto triploid stage 22 embryos followed by ploidy analyses of their hemopoietic cells revealed that both thymocytes and erythrocytes in early larvae are derived from the ventral blood islands (VBI), whereas those in late larvae and adults come mainly from the dorsolateral plate (DLP). To study how the VBI cells of embryos at stage 22 participate in hemopoiesis, a number of interspecific chimeras were produced in X. laevis and X. borealis embryos. Sections of the chimeras at various developmental stages were examined by employing the unique stainability of X. borealis nuclei to quinacrine as a marker; the results show that the VBI-derived cells enter into the circulation around stage 35/36, and that some of them leave the blood vessels to migrate interstitially through the mesenchyme toward the thymic rudiment during stages 43-45. A minor population of the VBI-derived cells was also found extravascularly in the mesonephric primordia. In contrast to the VBI, the DLP derived cells contributed to the hemopoietic cell population not in early larvae, but in late ones as a major constituent in the mesonephros, thymus, liver, and peripheral blood. PMID- 4018412 TI - Hormonal regulation of dopa decarboxylase during a larval molt. AB - Cuticular sclerotization in insects requires dopamine derivatives and thus the presence of dopa decarboxylase (DDC), the enzyme which converts dopa to dopamine. During the last half of the larval molt of the tobacco hornworm, Manduca sexta, beginning at 16 hr after head capsule slippage, the epidermal DDC activity increased fourfold. By contrast, allatectomized larvae which were destined to produce a melanized cuticle showed a sevenfold increase. This increase in DDC activity was prevented by infusion of 20-hydroxyecdysone (20HE) into the larva, indicating that the fall of the ecdysteroid titer is necessary for the increase. In vitro 20HE also prevented the increase in a dose-dependent manner when the epidermis was explanted at 16 hr after head capsule slippage but had less effect on epidermis explanted 3 hr later. Both 5 micrograms/ml alpha-amanitin and 100 micrograms/ml cycloheximide also prevented the increase. Application of juvenile hormone I showed that the critical period for determination of the level of the later increase in DDC activity was about 4 hr after head capsule slippage at the peak of the ecdysteroid titer. Apparently then the rise and fall of ecdysteroid regulate different aspects of DDC synthesis, the rise determining its later appearance and the fall timing this appearance. PMID- 4018413 TI - Regulation of lysosomal alpha-mannosidase-1 synthesis during development in Dictyostelium discoideum. AB - The cellular specific activity of lysosomal alpha-mannosidase-1 increases dramatically during development in Dictyostelium discoideum. alpha-Mannosidase-1 is composed of two subunits (Mr = 58,000 and 60,000) which are derived from a common precursor polypeptide (Mr = 140,000). Using enzyme-specific monoclonal antibodies we have determined that throughout development (a) the relative rate of precursor biosynthesis closely parallels the rate of accumulation of cellular enzyme activity and (b) the newly synthesized precursor is efficiently processed to mature enzyme (t1/2 less than 10 min). This indicates that the developmental accumulation of alpha-mannosidase-1 activity is primarily controlled by de novo enzyme synthesis. Furthermore, the change in the relative rate of enzyme precursor synthesis can be accounted for by an increase in the cellular level of functional alpha-mannosidase-1 mRNA during development. PMID- 4018414 TI - Phosphate transport by jejunal brush border membrane vesicles of the streptozocin diabetic rat. AB - We studied the effects of acute diabetes mellitus on jejunal transport of phosphate (32P) by rat brush border membrane vesicles (BBMV) using a Millipore filtration technique. Diabetes was induced by an intravenous (i.v.) injection of 50 mg/kg of streptozocin (STZ). Control and diabetic rats were studied 4 days after the induction of diabetes. In both control and diabetic rats, the presence of a sodium gradient significantly enhanced the uptake of 32P at 20 s and at 1, 2, 5, and 60 min as compared with potassium gradient conditions. Na+-dependent 32P uptake at 20 s and at 1 and 2 min was significantly greater in the diabetic BBMV compared with controls. Na+-independent 32P uptake in both diabetic and control BBMV was similar. To determine whether the enhancement of Na+-dependent 32P uptake in diabetic BBMV is due to an induction of Na+/phosphate cotransporter activity, or a change in Na+ permeability, two additional studies were conducted. Trans-stimulation studies nullifying all electrochemical gradients across the membranes were performed. In diabetic BBMV, 32P uptake at all time points was significantly greater than corresponding values in controls, indicating an increase in the activity of Na+/phosphate cotransporters. 22Na uptake into BBMV at 30 s and at 1, 2, and 60 min was not different between diabetics and controls, indicating that Na+ permeability is not altered in diabetes. Furthermore, kinetic studies using phosphate concentrations between 0.05 and 2.5 mM indicate a significant increase in Vmax capacity of diabetic rats compared with controls without a change in Km values.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4018415 TI - Sequential studies of glucose tolerance and red blood cell insulin receptors in normal human pregnancy. AB - Insulin binding to erythrocytes was sequentially studied in 12 healthy pregnant women during the anabolic (11-22 wk) and the catabolic (31-38 wk) gestational phases. For comparison, we studied 12 nonpregnant subjects at mid-luteal and mid follicular menstrual phases. Oral glucose tolerance tests were also performed during these studies. There was a progressive worsening of the glucose tolerance from the anabolic to the catabolic phase associated with fasting hypoglycemia and hyperinsulinemia. The worsening of glucose tolerance was accompanied by a progressive increment of insulin secretion. Insulin binding to red blood cells increased progressively from the anabolic to the catabolic phase, due to an increased number of receptors per cell, associated with a reduction in the apparent affinity at the low occupancy levels. We concluded that the insulin resistance of pregnancy was not accompanied by an impaired binding of insulin to its receptors, at least in the RBC. The data suggest that the defect of insulin action lies at a site distal to the receptor. PMID- 4018416 TI - Long-term prognosis after myocardial infarction in men with diabetes. AB - Men (1306) who survived a first myocardial infarction (MI) were studied. The mean follow-up time was 6.5 yr, and at the end of the follow-up period survival status was known for all patients. By the time of the MI the prevalence of diabetes was 5.6%. Patients with and without diabetes were compared. There were no differences in the estimated primary or secondary risk. The cumulative survival rate 1, 2, and 5 yr after the MI was 82, 78, and 58% among the diabetic subjects compared with 94, 92, and 82% among the nondiabetic subjects (P less than 0.001). The difference remained even after allowance for age and estimated secondary risk in a multivariate regression analysis. There were no differences in mortality rates among patients with type I diabetes compared with type II diabetes, nor among patients treated with diet alone, sulfonylurea, or insulin, but the numbers were small. The cumulative rate of reinfarctions after 1, 2, and 5 yr was 18, 28, and 46% in diabetic subjects and 12, 17, and 27% in nondiabetic subjects (P = 0.004). A history of diabetes was an independent secondary risk factor among male survivors of a first MI with respect to deaths and reinfarctions. PMID- 4018417 TI - Human insulin receptor gene. Data supporting assignment to chromosome 19. AB - Somatic cell hybrid clones constructed by crossing human skin fibroblasts with mouse L cells have been examined for expression of human insulin receptors, using a monoclonal antibody directed against the human insulin receptor. Data obtained in this study support the assignment of the human gene for the insulin receptor to chromosome 19. PMID- 4018418 TI - Proceedings of a conference on insulin pump therapy in diabetes. Multicenter study of effect on microvascular disease. Introduction. The Kroc Collaborative Study Group. PMID- 4018419 TI - Proceedings of a conference on insulin pump therapy in diabetes. Multicenter study of effect on microvascular disease. March 21-25, 1983, Santa Ynez, California. PMID- 4018420 TI - Conference on insulin pump therapy in diabetes. Multicenter study effect on microvascular disease. Studies of retinopathy. Methodology for assessment and classification with fundus photographs. AB - A major goal of the study was to assess the methodologies available for the quantification of retinal lesions suitable for application in trials of metabolic management. We describe the methods used for grading stereoscopic color fundus photographs. Overall retinopathy severity level for each eye ranging from normal (level 10) to high-risk category (level 70) was assigned on the basis of gradings of individual lesions. Change in retinopathy severity level over the 8-mo period was detected in 3-62% of patients, depending on the method used and the definition of change. Lesions responsible for change in level were mainly retinal infarcts (soft exudates) and intraretinal microvascular abnormalities. PMID- 4018421 TI - Conference on insulin pump therapy in diabetes. Multicenter study of effect on microvascular disease. Assessment of fluorescein angiograms. AB - Quantitation of the earliest changes in abnormal retinal morphology using fluorescein angiography is potentially superior to retinal photography. However, the critical importance of flawless technique, limitations in the size of the field available for detailed study, and observer variability constitute major disadvantages. A protocol describing standards of photography and of injection was developed. Methodology for counting microaneurysms (Ma) was developed at a central laboratory and applied in suitable photographs obtained at 0 (baseline), 4, and 8 mo in 68 patients. Counts of "definite" or "possible" Ma were made on films projected under standard conditions by two observers known to achieve consistently reproducible results. Semiquantitative assessment of diffusibility of fluorescein reflecting capillary leakage was performed in 61 patients. Leakage was graded according to three degrees of severity permitting study of observer variation, concordance of change in pairs of eyes, and treatment effects. The average number of Ma at baseline was slightly higher in the continuous subcutaneous insulin infusion (CSII) group than in the conventional insulin treatment (CIT) group, but the difference was not statistically significant at the 0.05 level. At both 4 and 8 mo, definite Ma were more prevalent in the CSII group, and the difference was statistically significant at the 0.05 level using both parametric and nonparametric tests. In 27 CSII and 23 CIT patients having complete sets of 0, 4, and 8-mo photographs, Ma counts increased during the 0-4 mo interval. During the 4-8 mo interval, a further increase occurred in the CSII group but contrasted with a decrement observed in the CIT group, which showed no net change from baseline.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4018422 TI - Eight-month correction of hyperglycemia in insulin-dependent diabetes mellitus is associated with a significant and sustained reduction of urinary albumin excretion rates in patients with microalbuminuria. AB - Persistent Albustix-positive proteinuria and subsequent chronic renal failure are frequently encountered in insulin-dependent diabetes mellitus (IDDM). Rates of decline of renal function may be modified by treatment of accompanying hypertension, but studies of the effects of long-term continuous subcutaneous insulin infusion (CSII) on deterioration of renal function provide no statistically significant evidence of benefit of near-normoglycemia. However, short-term studies in IDDM subjects with negative Albustix tests but subclinically raised levels of albumin excretion rate (AER) have shown that treatment with CSII significantly reduces this microalbuminuria. The prospective, controlled 8-mo Kroc Collaborative Study therefore offered the opportunity of examining more protracted effects of CSII-induced metabolic correction upon microalbuminuria. Twenty-four-hour urine collections obtained at baseline, 4, and 8 mo were available from 59 Albustix-negative patients. Beta 2-microglobulin excretion was normal. The 39 normoalbuminuric (AER less than 12 micrograms/min) patients did not differ from the 20 microalbuminuric (AER elevated between 13.2 and 192.6 micrograms/min) with respect to distributions of age, sex, and duration of diabetes. In both the normoalbuminuric and the microalbuminuric groups studied at 4 and 8 mo, percent glycosylated hemoglobin (%HbA1) and mean blood glucose were significantly decreased during CSII compared with baseline values, whereas no change occurred in the group continuing their conventional insulin therapy (CIT). AER did not differ between CIT and CSII treatments in the normoalbuminuric group. AER fell significantly in the CSII-treated microalbuminuric patients at 4 (P less than 0.05) and 8 (P less than 0.01) mo but showed no consistent change in the CIT microalbuminuric group.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4018423 TI - Two-year experience with continuous subcutaneous insulin infusion in relation to retinopathy and neuropathy. AB - Thirty patients with insulin-dependent diabetes mellitus (IDDM) who had advanced background retinopathy were randomized to unchanged conventional treatment (UCT) or to continuous subcutaneous insulin infusion (CSII). They were followed prospectively for 2 yr. The mean blood glucose and hemoglobin A1C (HbA1C) were significantly lower in the CSII group than in the UCT group. The mean blood glucose and HbA1C did not change from the first to the second year in either of the treatment groups in spite of less frequent home-monitoring of blood glucose and less frequent outpatient visits during the second year. Four patients in the CSII group and five in the UCT group developed proliferative retinopathy. However, a marginally significant trend was found toward more frequent improvement of retinal morphology in the CSII group (47%) than in the UCT group (13%). Beat-to-beat variation was found to deteriorate significantly with UCT compared with a nonsignificant improvement with CSII therapy. Vibration sense was unchanged in both treatment groups. It is concluded that near-normal blood glucose levels can be maintained with CSII therapy in spite of less frequent home monitoring of blood glucose and outpatient visits. Furthermore, established background retinopathy may progress to proliferative retinopathy in spite of 2 yr of near-normal blood glucose levels. However, a marginally significant trend toward more frequent improvement of retinal morphology was found among CSII treated patients compared with conventionally treated patients. Large-scale, prospective, randomized studies are needed to confirm these results. PMID- 4018424 TI - Chromosome 15 in Prader-Willi syndrome. AB - Nineteen children with the clinical features of Prader-Willi syndrome were karyotyped, using both routine Giemsa banding and high-resolution techniques. Chromosome abnormalities involving chromosome 15 were found in 10, entirely normal chromosomes in five and for the remaining four the findings were either equivocal or difficult to interpret. There was no clinical distinction between cases with and without the chromosome anomaly. Examination of three parents and a group of controls showed that the proximal end of the long arm of chromosome 15 may have a considerable degree of normal variation, which can make interpretation difficult. PMID- 4018425 TI - Neurological manifestations in abused children who have been shaken. AB - Four infants with the 'shaken infant syndrome' are described. None had skull fractures and only one had a subdural hematoma. All had extensive retinal and pre retinal hemorrhages. Follow-up computerized tomography showed severe brain atrophy, multiple hypodense areas and ventricular enlargement. Three of the patients suffered severe, permanent brain damage, with mental retardation, spasticity and blindness. It is suggested that the underlying pathogenesis of this syndrome is acutely increased intrathoracic pressure, transmitted into the head to cause multiple venous infarctions. Retinal and pre-retinal hemorrhages are cardinal features of this syndrome and their presence should raise the suspicion of this form of battering in the absence of the 'classical' signs of battering. PMID- 4018426 TI - Neurological signs in congenital iodine-deficiency disorder (endemic cretinism). AB - Neurological examinations were made of 67 children and adults with congenital iodine-deficiency disorder (endemic cretinism) in four rural villages in highland Ecuador. There was a distinct and readily identifiable pattern of neurological deficits. These included, to varying degrees: deaf-mutism or lesser degrees of bilateral hearing-loss or dysarthria; spasticity, particularly involving the proximal lower extremities; mental deficiency of a characteristic type; and rigidity and bradykinesia. Not all of these elements were found in all cases. Less common features were strabismus, kyphoscoliosis and frontal-lobe signs. There were exceptional cases with hypotonia. In contrast, cerebellar function was largely spared, as were functions of emotion and attention, vegetative and autonomic functions, social interaction, and probably memory, except in the most severely involved. PMID- 4018427 TI - Consideration of genetic factors in cerebral palsy. AB - Sixty-two patients with cerebral palsy seen consecutively in a pediatric neurology practice were submitted to a prospective protocol which tabulated their neurological findings, birth and developmental histories and an extensive neurodevelopmental pedigree. Their family histories were compared with those of three control groups, consisting of 62 children with headaches, 62 with school/behavior problems and 62 random normal children. The family histories of the cerebral-palsied children revealed an unusual number of relatives with cerebral palsy, mental retardation and seizures. This study suggests that a large proportion of cerebral-palsied individuals may be predisposed to aplasia/hypoplasia of neural tissue. Some affected by presumably static 'brain damage' may in later years develop indolent degenerative disease. Indirect genetic factors may also play a major predisposing role in cerebral palsy of proven postnatal/perinatal onset. PMID- 4018428 TI - Early detection of brainstem glioma using brainstem auditory evoked potentials. AB - Brainstem tumor was suspected in an 11-year-old boy presenting with a painless lateral rectus palsy, on the basis of abnormal brainstem auditory evoked potentials (BAEP), despite normal computed tomographic studies, the diagnosis being confirmed by biopsy. The BAEP improved after radiation therapy, but their later deterioration heralded the onset of recurrence two weeks before any adverse clinical symptoms appeared. The value of BAEP studies in the early detection of brainstem lesions and in monitoring their progress, is discussed. PMID- 4018429 TI - Neuromotor maturation and psychological performance: a developmental study. AB - Groups of 50 normal kindergarten and 50 first-grade children were examined three times at six-month intervals on the extended neuromotor examination for children, as well as on measures of reading achievement and language performance. The joint effect of five neuromotor measures accounted for a substantial percentage of variance in reading achievement and language performance 12 months later. As a global measure, neuromotor status therefore may constitute a reliable, independent criterion of developmental age for psychological investigations of young, normal children. The best individual predictors of psychological outcome were mirror movements and speed of timed motor repetitions, while reading achievement and automated naming speed were the dependent measures most closely associated over time with neuromotor status. Such findings suggest that the individual motor signs may also provide indirect clues about the presumed functional relationship between development of motor co-ordination and language competence. PMID- 4018430 TI - Physical development of hyperactive boys. AB - Anthropometric data were collected on groups of seven-year-old Dunedin (New Zealand) boys, identified as hyperactive-only, aggressive-hyperactive, aggressive only and non-aggressive/non-hyperactive. Measures taken included stature, weight, skeletal maturity, mid-upper arm circumference, triceps and subscapular fatfolds and body-mass index. The hypothesis that hyperactive-only boys would show delayed maturation, as indicated by lower bone-age, was not confirmed. However, these boys had significantly smaller mid-upper arm circumference, triceps fatfold and body-mass index than the other groups. The results suggest that body leanness may discriminate 'pure' hyperactive boys from aggressive-hyperactive boys. PMID- 4018431 TI - Congenital rupture of a neuropathic bladder: report of a case. AB - A case of intra-uterine rupture of a neurogenic bladder in a female child with spina bifida is reported, together with the unusual histological appearances of detrusor-muscle atrophy at the site of rupture. The literature on ruptured bladder in the neonatal period is reviewed. PMID- 4018432 TI - Cachexia in a mentally retarded adolescent secondary to mandibular dislocation. AB - A 19-year-old mentally retarded male's cachexia, of five months duration, was attributed to a previously undetected anterior dislocation of the mandible. After reduction of the mandible he improved markedly, with better appetite and rapid weight-gain. PMID- 4018433 TI - Pyridoxine for neonatal seizures: an unexpected danger. AB - A case of pyridoxine-dependent seizures is reported. Administration of pyridoxine to an infant after a long period of convulsions was followed by acute hypotonia. Other cases have been reported in the literature, in one of which assisted ventilation was required. A possible mechanism for this alarming outcome is discussed, and it is suggested that resuscitation facilities should be quickly available during such trials. PMID- 4018434 TI - Brainstem glioma presenting as paroxysmal headache. AB - An unusual case of brainstem glioma is described. The distinctive features were long duration (at least six months) of headaches preceding the appearance of neurological signs, and the intermittent, paroxysmal nature of the symptoms, often precipitated by postural change. The mechanism of headache induced by brain tumor is discussed, and a possible cause for the headaches in this patient is suggested, involving intermittent obstruction of CSF flow. PMID- 4018435 TI - Recovery from cortical blindness. PMID- 4018436 TI - Congenital hypothyroidism. PMID- 4018437 TI - Spastic paralytic dislocation of the hip. PMID- 4018438 TI - Citrate and calcium secretion in the pure human pancreatic juice of alcoholic and nonalcoholic men and of chronic pancreatitis patients. AB - Citrate, calcium and protein have been estimated in pure pancreatic juice after a secretin and a CCK injection in 4 patients presenting with alcoholic calcified pancreatitis (ACP), 10 controls without evidence of pancreatic disease, drinking more than 130 g alcohol/day, and 10 controls without evidence of pancreatic disease, drinking less than 20 g alcohol/day. Citrate is normally secreted in the pancreatic juice and this secretion increases in parallel with protein after CCK injection. Citrate secretion is significantly decreased in the two alcoholic groups. Calcium secretion is increased in the ACP, and reasons are presented to suggest that this may be due to lesions of the ducts. These modifications could play a role in the formation of pancreatic stones which are mostly built up of calcium carbonate. PMID- 4018439 TI - Plasma apolipoprotein A-IV levels decrease in patients with chronic pancreatitis and malabsorption syndrome. AB - An immunochemical method was developed for measurements of serum levels of apolipoprotein A-IV (apo A-IV). Using this technique, we found decreased levels of apo A-IV in patients with chronic pancreatitis and malabsorption syndrome and these low levels of apo A-IV in a patient with malabsorption syndrome were overcome after appropriate oral nutrition. Thus, measurements of apo A-IV may provide a good index for the assessment of fat intake and absorption. PMID- 4018440 TI - Effect of filtrate containing Clostridium difficile toxin on rectal mucosa maintained in organ culture. AB - Rectal biopsies were maintained in organ culture over a 24-hour culture period, with good preservation of histological architecture. A filtrate containing Clostridium difficile toxin significantly inhibited the rise in epithelial alkaline phosphatase activity normally seen during culture. This effect was abolished by pre-incubation of the filtrate with Clostridium sordellii antitoxin, or heat inactivation. This effect is most probably due to a toxin of C. difficile. The method provides a new quantitative approach to the study of luminal toxins as possible pathogenic agents in idiopathic inflammatory diseases of the colon. PMID- 4018441 TI - Gastrin and gastric secretion in patients with recurrent peptic ulceration- unexpected correlations. AB - The role of gastrin in the pathogenesis of recurrent peptic ulceration is not established although it is known that plasma gastrin levels are frequently elevated after vagotomy. This study aims to determine whether there is a relationship between gastrin and gastric secretion in patients with and without recurrent ulceration after surgery for duodenal ulceration (DU). The basal acid output (BAO) in 23 and the peak acid output to pentagastrin (PAOPg) in 10 patients with symptomatic recurrent ulcers after DU surgery were determined along with the BAO and PAOPg in 10 control patients who were asymptomatic following DU surgery. The fasting plasma gastrin was determined in all patients and correlated with the acid output. An inverse correlation was demonstrated between the BAO and plasma gastrin in the asymptomatic patients (p less than 0.05) and the patients with proven recurrent ulcers (p less than 0.01) and there was a direct correlation between the PAOPg and plasma gastrin in the recurrent ulcer group (p less than 0.05) which was not observed in the control group. It is suggested that in a subgroup of recurrent ulcer patients 'G cell hyperfunction' may occur and this may have a role in the aetiology of this condition. PMID- 4018442 TI - Comparative assessment of secretin and motilin responses to graded duodenal acidification in anaesthetised pigs. AB - The effects of graded duodenal acidification on plasma concentration of immunoreactive secretin, and motilin in portal vein (PV) and carotid artery (CA) were investigated in 6 anaesthetised pigs in which the proximal duodenum was excluded and sequentially irrigated with isotonic saline (pH 7.0) and with hydrochloric acid (HCl) delivered at successive rates of 2, 8 and 40 mM H+/40 min (pH of 2.8, 1.9 and 1.0, respectively) under a constant flow of 10 ml/min. The release of secretin was first observed at pH 1.9 (from basal 4.2 +/- 0.3 to a peak of 26.6 +/- 9.8 pM in PV and from 3.4 +/- 0.3 to 6.8 +/- 0.9 pM in CA) and further increased at pH 1.0 (peaks of 60.9 +/- 16.3 in PV and 16.8 +/- 2.6 pM in CA). In contrast, only the highest HCl concentration (pH of effluent: 1.0) induced significant increases of plasma motilin (PV: peak of 25.2 +/- 4.9 for basal 13.3 +/- 1.1 pM, CA: 14.3 +/- 2.4 for basal 10.5 +/- 0.6 pM). A sharp decrease of the plasma secretin and motilin concentration was observed when the venous drainage of the duodenal segment was occluded, followed by a rapid increase when the clamp was released. In the present experimental conditions, duodenal motilin-producing sites were less sensitive to graded luminal acidification than secretin cells. Thus, the release of duodenal motilin in response to variations of luminal pH may be expected to occur primarily from the most proximal part of the duodenum in physiological conditions. PMID- 4018443 TI - Toxicity of kidney bean (Phaseolus vulgaris) in rats: changes in intestinal permeability. AB - Rats fed on diets containing kidney bean showed increased intestinal permeability to intravenously injected 125I-labelled rat serum proteins after an intragastric challenge with bean proteins. The enhanced accumulation of radioactive serum proteins in the lumen and walls of the small intestine indicated increased vascular permeability. It is suggested that dietary lectins may, at least in part, be responsible for this loss of serum proteins and thus contribute towards the overall toxicity of kidney bean proteins. PMID- 4018444 TI - Absorption of urso- and chenodeoxycholic acid and their taurine and glycine conjugates in rat jejunum, ileum, and colon. AB - Chenodeoxycholic acid (cheno) and ursodeoxycholic acid (urso) dissolve cholesterol gallstones in man. Comparative studies of the absorption of cheno and urso are not available. The absorption of urso and cheno and their glycine and taurine conjugates in jejunum, terminal ileum, and colon of the rat were therefore determined in an open in situ perfusion system. Absorption of unconjugated urso and cheno in jejunum, ileum, and colon was similar. In the jejunum conjugated urso and cheno were absorbed only in minimal amounts. In the ileum glycine-conjugated urso was absorbed to a lower extent than glycine conjugated cheno (6.5 +/- 0.4 vs. 8.6 +/- 0.6 nmol/cm X h at 25 mumol/l bile acid concentration, p less than 0.05) and taurine-conjugated urso was absorbed less than taurine-conjugated cheno (6.4 +/- 0.5 vs. 8.1 +/- 0.7 nmol/cm X h, p less than 0.05). In the colon glycourso and taurourso were not absorbed, while glycocheno and taurocheno were absorbed in small amounts. The low reabsorption rates of urso conjugates in ileum and colon may contribute to the relatively low urso content in bile during urso treatment. PMID- 4018445 TI - Mononeuritis in acute viral hepatitis. AB - We describe the cases of 4 adults with acute viral hepatitis A or B in whom mononeuritis affecting a cranial nerve or a nerve of a limb developed. The features of this neuropathy were the following: (a) the prevalence of mononeuritis in patients with acute viral hepatitis was low; (b) this complication developed in the early phase of acute viral hepatitis in most of our patients; (c) the onset of mononeuritis was sudden in most of them; (d) the course of mononeuritis was protracted. Mononeuritis might be the consequence of ischemia resulting from vasculitis. PMID- 4018446 TI - Identification of mucus glycoprotein fatty acyltransferase activity in human gastric mucosa. AB - The enzymatic activity which catalyzes the transfer of palmitic acid from palmitoyl coenzyme A to gastric mucus glycoprotein was demonstrated in antral and fundic mucosa of normal human stomach. Subcellular fractionation studies revealed that with both types of mucosa the enzyme activity was present in the microsomal fraction. The antral and fundic mucosa also exhibited similar enzyme activities, showed identical pH optimum, and required detergent, NaF and dithiothreitol. Optimum enzymatic activity for fatty acylation of mucus glycoprotein was obtained with 0.5% Triton X-100, 25 mM NaF, and 2 mM dithiothreitol at a pH of 7.4. The 14C-labeled product of the reaction comigrated on CsCl density gradient centrifugation with gastric mucus glycoprotein and contained the ester-bound palmitic acid. PMID- 4018448 TI - European Association for the Study of Diabetes: 1965-1984. PMID- 4018447 TI - Effect of short-term and long-term treatment with a steroidal oral contraceptive on the intestinal absorption of nutrients in vitro in female rats. AB - The effect of steroidal oral contraceptive (SOC), comprising megestrol acetate (5 mg/kg body weight) plus ethinyl estradiol (0.05 mg/kg body weight), administered daily by stomach tube for 5, 15, 30 and 90 days, on the intestinal uptake of nutrients such as glucose, amino acids and calcium has been investigated in vitro in female rats. The administration of SOC for 5 days did not affect the uptake of nutrients, but treatment for 15, 30 and 90 days led to a progressive and significant increase in the uptake of glucose and amino acids. The calcium uptake was increased in the groups treated for 5 and 15 days, but decreased after 30 and 90 days of treatment. Kinetic studies done on glucose uptake indicated that the steroid contraceptive might be inducing the transport carrier protein of this nutrient, as elevation in Vmax was observed in the group treated for 30 days. There was no change in brush border membrane phospholipid and cholesterol contents after 30 and 90 days of treatment, but a significant increase in phospholipid after 5 and 15 days of treatment was observed. This study suggests that SOC treatment significantly altered the intestinal absorptive functions and the effect appears to be on the carrier-mediated transport of glucose. PMID- 4018449 TI - Sera from type 2 (non-insulin-dependent) diabetic and healthy subjects contain different amounts of a very low molecular weight growth peptide for vascular cells. AB - Diabetic angiopathy may be due, in part, to increased growth in vascular cells. We have investigated serum growth factors in Type 2 (non-insulin-dependent) diabetic and healthy subjects and their effect on cultured human arterial smooth muscle cells and fibroblasts. Removal of the dialyzable serum fraction (mol. wt. less than 12,000) reduced the growth effect of the diabetic sera by 37% (2p less than 0.005) and of the non-diabetic sera by only 8% (2p less than 0.01). In contrast, there was no difference in growth stimulation between the dialyzed diabetic or non-diabetic sera. Complete recovery of the dialyzable serum growth fraction was also obtained at a mol. wt. below 3,500. Ten times the concentration of the low molecular weight growth factor (mol. wt. less than 3,500) from diabetic sera stimulated growth of fibroblasts or arterial smooth muscle cells by a mean of 243% or 174% and from non-diabetic sera by a mean of 146% or 137%, respectively (2p less than 0.01). The growth stimulating potency of this serum fraction (mol. wt. less than 3,500) contained in 10% diabetic sera, was two to ten times higher than that of human growth hormone or insulin, added in amounts equivalent to 10% or physiological serum concentrations. This diabetic serum growth factor was further characterized by: (1) linear dependence of growth stimulation over a concentration range of twenty times and by (2) reduction of the growth stimulating activity to control levels by pretreatment: (a) at 95 degrees C for 30 min, or (b) with two different proteases: Serva pronase E (Streptomyceus griseus) or Calbiochem protease (Subtilisin calsberg).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4018450 TI - Tropical pancreatic diabetes in South India: heterogeneity in clinical and biochemical profile. AB - Clinical and biochemical studies were carried out in 33 patients with diabetes secondary to chronic calcific, non-alcoholic pancreatitis (tropical pancreatic diabetes) and in 35 Type 2 (non-insulin-dependent) diabetic patients and 35 non diabetic subjects. Despite lower body mass indices, only 25% of patients with tropical pancreatic diabetes had clinical evidence of malnutrition. There was no history of cassava ingestion. Mean serum cholesterol concentration was significantly lower in the tropical pancreatic diabetic patients (p less than 0.01) in comparison with the Type 2 diabetic patients or non-diabetic subjects, due to a significantly decreased concentration of LDL cholesterol (p less than 0.01) and VLDL cholesterol (p less than 0.05). Basal and post-glucose stimulated concentrations of serum C-peptide were highest in those pancreatic diabetic patients (n = 11) who responded to oral hypoglycaemic drugs, intermediate in the majority (n = 17), who were insulin dependent and ketosis resistant and negligible in a small sub-group (n = 5) who were ketosis prone. The occurrence of microangiopathy in pancreatic diabetic patients was common and similar to that in Type 2 diabetic patients. Thus, tropical pancreatic diabetes in South India appears to be heterogeneous with respect to level of nutrition, severity of glucose intolerance, B-cell function, response to therapy and the occurrence of microvascular complications. PMID- 4018451 TI - Influence of mebendazole administration on metabolic control in type 1 (insulin dependent) diabetic patients. PMID- 4018452 TI - Physical activity and prevalence of diabetes. PMID- 4018453 TI - Transcapillary colloid osmotic gradient, plasma volume and interstitial fluid volume in long-term type 1 (insulin-dependent) diabetes. AB - Plasma and subcutaneous colloid osmotic pressure, transcapillary escape rate of albumin, plasma volume and extracellular fluid volume were measured in 10 long term Type 1 (insulin-dependent) diabetic patients without clinical nephropathy. Interstitial colloid osmotic pressure was reduced compared with normal subjects (12.9 +/- 3.0 versus 15.8 +/- 2.7 mmHg, p less than 0.05) and the transcapillary colloid osmotic gradient increased (17.0 +/- 2.4 versus 12.8 +/- 2.7 mmHg, p less than 0.01). Plasma volume was in the normal range and interstitial fluid volume increased by approximately 21% compared with normal subjects (p less than 0.01). Transcapillary escape rate of albumin was significantly increased compared with normal subjects (8.9 +/- 1.9 versus 5.1 +/- 1.6% h, p less than 0.01). A negative correlation was found between the transcapillary colloid osmotic gradient and interstitial fluid volume (r = 0.6, 0.01 less than p less than 0.05). These results suggest that the increased small vessel permeability in long-term diabetes leads to wash-out of interstitial proteins and the resulting increased transcapillary colloid osmotic gradient tends to preserve the plasma volume and to limit the tendency to increased interstitial fluid volume. PMID- 4018454 TI - Inhibition of aortic histamine synthesis by alpha-hydrazinohistidine inhibits increased aortic albumin accumulation in experimental diabetes in the rat. AB - We examined the interrelationship between inhibition of aortic histamine synthesis through inhibition of aortic histidine decarboxylase and intra-aortic albumin accumulation in rats made diabetic by a jugular vein injection of 60 mg/kg of streptozotocin under ether anesthesia. Animals were held for 4 weeks following overt manifestation of diabetes. At the end of 3 weeks, at least six animals in each of the diabetic and non-diabetic groups received intra-peritoneal injections of alpha-hydrazinohistidine (25 mg/kg at 12 h) for the last 7 days. Aortic albumin accumulation was measured by quantification of aortic uptake of fluorescein isothiocyanate conjugated to rat serum albumin injected in the jugular vein 1 h before sacrifice. The aortic albumin mass transfer and flux rates of the diabetic group were more than 300% higher than that of the control group; alpha-hydrazinohistidine treated diabetic rats had aortic albumin mass transfer rates equivalent to control values. The aortic albumin content was nearly tenfold higher in untreated diabetic rats, but again treatment with alpha hydrazinohistidine returned this to control values. These data offer strong support to the premise that accelerated aortic histamine synthesis, which occurs in experimental diabetes, is an important mediator of increased aortic macromolecule uptake, and as such, may be one component of the multitude of factors responsible for increased susceptibility of atherosclerosis among individuals having diabetes mellitus. PMID- 4018456 TI - A demonstration of cellular interactions during the formation of mesoderm and primordial germ cells in Pleurodeles waltlii. AB - Animal, vegetal, dorsal and ventral blastomeres of eight-cell embryos of the urodele Pleurodeles waltlii were isolated and cultured for 15 days. The four animal blastomeres produced vesicles delimited by an irregularly shaped epidermis. In all other explants, the formation of mesodermal structures occurred, which can be interpreted as the result of inductive interaction, occurring during segmentation, between the ectodermal animal cap and vegetal yolk mass. Primordial germ cells (PGCs), which formed in 78% of cases when the presumptive ventral half to the embryo was cultured, occurred in only 48% of cases when the two ventral vegetal blastomeres were cultured alone. The absence of PGCs in the explants emanating from the four vegetal blastomeres is thought to have been due to inhibition of differentiation by notochord. This hypothesis has been confirmed by culture experiments in which the addition of presumptive chordomesoderm of young gastrulae prevented the differentiation of PGCs under conditions in which they are normally formed. These observations suggest that, in urodeles, PGCs do not arise from cells segregated as early as the eight-cell stage, but are the product of later inductive interaction between ectoderm and endoderm. PMID- 4018455 TI - Elevated levels of vasoactive intestinal peptide in the eye and urinary bladder of diabetic and prediabetic Chinese hamsters. AB - The eyes and urinary bladder of non-diabetic, prediabetic and diabetic Chinese hamsters were evaluated by radioimmunoassay and immunocytochemistry to determine the content and distribution of vasoactive intestinal peptide (VIP). The average concentration of VIP was increased in the eyes of all diabetic (pmol/g = 68%, pmol/organ = 50%) and prediabetic (pmol/g = 152%, pmol/organ = 115%) hamsters compared with age-matched non-diabetic animals. Immunocytochemistry showed that the elevation of VIP was primarily related to greater intensity of fluorescence of the nerve fibres in the vasculature of the choroid. The average content of VIP in the urinary bladder was greater in diabetic animals only on the basis of pmol/organ (135%) and in prediabetics on the basis of pmol/g (87%) compared with non-diabetic animals. Qualitative immunocytochemistry suggested that the elevated level of VIP was related to a larger distribution of nerve fibres in the urinary bladder of diabetic hamsters. The high level of VIP in the eyes and urinary bladder of diabetic and prediabetic hamsters is an interesting observation which should receive further study to determine whether it is an aetiological agent underlying the pathogenesis of ophthalmic complications and neurogenic bladder or the result of some pathological process which affects these organs. PMID- 4018457 TI - A fine analysis of glucose-phosphate-isomerase patterns in single preimplantation mouse embryos. AB - Mouse embryos were derived from eggs heterozygous for alleles of the dimeric enzyme glucose phosphate isomerase (Gpi-1a/Gpi-1b) that had been fertilized with sperm carrying a third allele (Gpi-1c). This particular combination makes it possible to study the activity of the paternally derived as well as the maternally derived genes, the persistence of oocyte-coded enzyme throughout early development and the possible simultaneous expression of both the paternally derived allele and the maternal message. The different isozymes present in single embryos were separated by electrophoresis. The results show that the oocyte-coded glucose phosphate isomerase is gradually replaced by embryo-coded enzyme. Expression of the paternally derived allele was first detected at the morula stage, during which the translation of the maternally derived message seemed to be either exhausted or below the detection limit of our system. Some oocyte-coded enzyme persisted until after implantation. PMID- 4018458 TI - Reactivity of five N-acetylgalactosamine-recognizing lectins with preimplantation embryos, early postimplantation embryos, and teratocarcinoma cells of the mouse. AB - The expression of receptors for N-acetylgalactosamine-recognizing lectins, namely Helix pomatia agglutinin (HPA), Sophora japonica agglutinin (SJA), Bauhinia purpurea agglutinin (BPA), Vicia villosa agglutinin (VVA), and Wistaria floribunda agglutinin (WFA) was studied in early mouse embryos and teratocarcinoma cells. Each of these lectins as well as Dolichos biflorus agglutinin (DBA) bound differently to early embryonic cells, with the exception of VVA and WFA which showed indistinguishable reactivities. SJA reacted intensely with visceral endoderm, but hardly at all with parietal and primitive endoderm. Therefore, SJA will be useful for analyzing the mechanism of visceral-endoderm formation. Furthermore, the inner cell mass (ICM) of early blastocysts reacted intensely with DBA, while the ICM of late blastocysts reacted only faintly with this lectin. Primary endoderm derived from the ICM reacted faintly with SJA, HPA, and DBA, and these reactivities increased again during the differentiation of the endoderm. Therefore, these three lectins could be used in the analysis of early stages during the differentiation of endoderm from the ICM. The results illustrate the highly complex nature of developmentally regulated alterations of cell-surface carbohydrates during the early stages of embryogenesis. PMID- 4018459 TI - Basement membrane in differentiating mesonephric and paramesonephric ducts of male and female rat fetuses. AB - The differentiation of male and female rat genital ducts and their basement membranes were studied by light- and electron-microscopic localization of type-IV and -V collagen, laminin, and heparan sulfate proteoglycan at the fetal ages of 15-21 days. At 15 days, the basement membrane of the mesonephric duct was continuous in both sexes, whereas on the medial side of the paramesonephric duct, it was incomplete. The male mesonephric duct remained enveloped by a continuous basement membrane. Increasing accumulation of basement-membrane material in the periductal mesenchyme was regarded as incipient epididymal differentiation. Local expansions and slow degradation of the basement membrane were noted in the regressing female mesonephric duct. The female paramesonephric duct had acquired a continuous basement membrane by the age of 16 days. At this age, the incomplete basement membrane in the medial side of the male paramesonephric duct disappeared, and breaks in the lateral portion appeared. The formation of epitheliomesenchymal contacts and basal cytoplasmic blebs in the epithelial cells of the regressing paramesonephric duct coincided with the disappearance of the basement-membrane material in the condensed periductal mesenchyme. The asymmetric regression of the male paramesonephric duct was initiated in the immature medial side. The changes in the periductal matrix are indications of basic differences in the regulation of the development and regression of the genital ducts in different sexes. PMID- 4018460 TI - Permissive effect of glutamine on the differentiation of fetal mouse small intestine in organ culture. AB - The proximal third of the small intestine of 15-day-old mouse embryo can be cultured for 72 h at 37 degrees C. When Trowell-T8 medium is used, the integrity of the explants is maintained, but villi do not form and absorptive cells are poorly differentiated. However, when Leibovitz L-15 or RPMI-1640 medium is used, one can observe the formation of medium-sized villi, and absorptive cells in the explants are more differentiated. Since the chemical composition of T8 medium is quite different from that of the other two media, we decided to test the importance of two major differences, i.e., three amino acids and five vitamins, in order to find out which element(s) is necessary to permit the formation of intestinal villi. Subsequent testing demonstrated that the three amino acids are responsible for the effect on differentiation, and that glutamine is the only critical difference between T8 and the two other media. The results show that the addition of L-glutamine to T8 medium permits the formation of villi, the initiation of absorptive cell differentiation, an increase in DNA synthesis, and finally, an increase in the number of epithelial cells. These findings indicate that undifferentiated fetal mouse small intestine is able to express its phenotype in organ culture, even without any extrinsic regulatory influences, provided that L-glutamine is present at a sufficient level in the culture medium. The use of inhibitors indicated that L-glutamine may be essential as an energetic substrate and/or a precursor for glucosamine. PMID- 4018461 TI - Aggregation-deficient embryonal carcinoma cells: defects in peanut agglutinin (PNA) receptors. AB - The components involved in cell adhesion were studied using the H6 line of embryonal carcinoma cells. H6 cells are especially suitable for studies on cell interactions, since genetic mutants can be selected, and various processes of cell adhesion can be controlled by regulating the calcium concentration in the medium. Three aggregation-defective variants of H6 were isolated, all of which showed reduced binding of the lectin, peanut agglutinin (PNA). Quantitation of PNA receptors on the cell surface by immunoprecipitation of iodinated surface proteins indicated that these receptors were reduced on the variants by one-half to one-quarter. The separation of immunoprecipitated PNA receptors on sodium dodecyl-sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) demonstrated that one type of receptor, with an apparent molecular weight of 94 kilodaltons, was reduced. Parental and variant cells bind similar quantities of concanavalin A and soybean agglutinin, suggesting that there is no generalized effect on major glycoproteins. Thus, the defect in aggregation and the defect in the 94 kilodalton protein may be correlated, and this glycoprotein may have a role in the mediation of H6 cell-cell adhesion. PMID- 4018462 TI - Anatomic distribution of lectin binding sites in mouse testis and epididymis. PMID- 4018463 TI - May early exercise testing after myocardial infarction predict the extent of coronary artery disease? AB - To determine whether exercise testing performed soon after myocardial infarction may predict the degree of coronary artery disease, 78 patients performed stress testing and coronary angiography 15 +/- 5 and 64 +/- 35 days, respectively, after myocardial infarction. Out of 34 patients with a positive test, 22 (65%) demonstrated a multivessel disease, and 37 (84%) out of 44 patients with a negative test had normal coronary angiograms or single vessel disease (p = .0006). In addition to stress testing, no clinical parameter considered (infarct location, heart failure and cardiomegaly) was predictive of the extent of coronary artery disease. PMID- 4018464 TI - [Limits of mental stress as an instrument for evaluative screening in recent myocardial infarction]. AB - In order to investigate whether stressors could induce ventricular arrhythmias or myocardial ischemia in the postinfarction period, 130 patients with recent myocardial infarction (1-2 months after the acute episode), after drug washout, were exposed to two stressors in a random sequence. Mental arithmetic and Sacks test (30 incomplete sentences with high emotional content) were used for 3 min, followed by 5 min recovery. Ninety % of the patients underwent an exercise test and 73% a 24 hour ambulatory monitoring in the same conditions. Ventricular arrhythmias occurred respectively in 21%, 26% and 86% of the patients during mental stress, exercise test and ambulatory ECG monitoring. The arrhythmias score (Italian Lown modified classification) was greater than or equal to 40 in 2% of the patients during mental stress and in 39% in the ambulatory ECG. Only 3 patients (2.3%) showed ST-segment depression greater than or equal to 1mm during mental stress vs. 30.7% during exercise. The double product threshold for ST segment shift was reached or exceeded during mental stress by 22% of the patients. The increments in heart rate and blood pressure were independent from each other, and similar in the two stress tests. Only the heart rate was slightly higher during mental arithmetic (p less than 0.01). In conclusion, the utilized short-lasting stressors were poorly effective in inducing myocardial ischemia and ventricular arrhythmias in patients with recent myocardial infarction. It is suggested to avoid the generalization of these results to patients with different pathophysiological conditions, taking on account the methodological limits of the study. PMID- 4018465 TI - [Evaluation of flecainide in the therapy of chronic ventricular arrhythmia using the acute oral load method]. AB - The efficacy of the new class Ic anti-arrhythmic (aa) drug, Flecainide, has been evaluated in patients (pts) affected by frequent and/or severe chronic ventricular arrhythmias (VA), as assessed by 24 hours Holter monitoring and maximal exercise stress testing. The protocol consisted in a preliminary screening with multiple aa drugs (average 6.0 per pt) using the acute oral drug testing. The most effective drug was then given for 72 hours and 24 hours Holter monitoring and exercise stress testing repeated; if the efficacy was confirmed, chronic treatment was initiated and control visits were repeated after 3, 6 and 12 months. The study population consisted of 27 pts; 22 (81%) were in Lown class 4A (18%) or 4B (63%). Eight pts (30%) had a previous (greater than 1 year) myocardial infarction, while in 14 (52%) no evidence of cardiac disease was found. During acute oral drug testing a positive response (reduction of PVC's greater than 90% and abolition of grades 4A and 4B) was obtained with Flecainide, 200 mg, in 20 pts (74%). In 6 pts (22%) no effect was observed, while a possible proarrhythmic effect was observed in 1 pt (4%). Eighteen pts entered the second phase of the study with an average dose of Flecainide of 175 mg b.i.d. In 83% of the pts there was a positive concordance between the acute oral testing and the 72 hours treatment, as in 15 out of 18 pts grades 4A and 4B were totally abolished and the mean frequency of PVC's was reduced by 99%. In 3 pts (17%) no response was observed. Flecainide increased significantly PR (37 msec), QRS (20 msec) and QTc (28 msec). The plasma levels attained with chronic therapy (846 ng/ml) were higher than those achieved with the acute oral testing (372 ng/ml). Mild side effects (dizziness, tremor and headache) were observed in 33% of the pts and were all eliminated by a 100 mg reduction in Flecainide dose. Fifteen pts entered the third phase (long term treatment): in this group there was a 93.3% correlation with phase two, as in 14 out of 15 pts there was a complete abolition of grade 4B arrhythmias, a 98.8% reduction of couplets and a reduction in the number of PVC's greater than 85%. This study shows that Flecainide is a quite powerful aa drug with modest side effects. Its efficacy against chronic VA is high, also when compared to the most effective and available aa drugs.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 4018466 TI - [Flecainide in the treatment of chronic ventricular arrhythmia]. PMID- 4018467 TI - [Intravenous administration of lidocaine and amiodarone in patients with acute myocardial infarction]. AB - Lidocaine (L) in still considered the drug of choice in the treatment of life threatening ventricular arrhythmias in the setting of acute myocardial infarction (A.M.I.): this is mainly due to its proved efficacy and high therapeutic index. Since however L has well defined electrophysiologic properties (class 1 B) and does not seem to be effective in all of these patients we compared its antiarrhythmic efficacy with the one of amiodarone (A), an antiarrhythmic agent provided of electrophysiologic properties quite different from L (class 4) and usually well tolerated. Twenty-five consecutive patients with A.M.I. without haemodynamic consequences, were randomly assigned to L (bolus of 1 mg/kg followed by an infusion of 10 mg/min for 20 minutes and thereafter of 1,5 mg/min) or A (bolus of 5 mg/kg and an eventual repeat dose of 150 mg followed by an infusion of 1,8 g/24 h) The baseline arrhythmia was classified as Lown class 2 ore more in all the patients. The ventricular arrhythmias were completely relieved in 47% of the patients assigned to L and in 60% of those treated with A (p = N.S.); a minor efficacy was found in 40% of the patients of both groups; in two cases ventricular fibrillation occurred after the acute infusion of L. The antiarrhythmic effectiveness kept fit with both drugs over a 24 hours period. A prolongation of QTc interval was found to occur both after the bolus and 24 hours of treatment with A. In addition A provoked a slight decrease of systolic blood pressure. No important side effects were observed with both drugs regimens.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4018468 TI - [Intravenous amiodarone in the therapy of paroxysmal supraventricular tachycardias]. AB - The Authors evaluated the effectiveness and the tolerance of intravenous Amiodarone in 50 cases of recent onset paroxysmal supraventricular tachyarrhythmias. Fifty consecutive patients, aged 17 to 84 (mean 52 years), presenting with paroxysmal supraventricular tachycardia (PSVT, 33 cases) or atrial flutter (11 cases) or atrial fibrillation (6 cases), were given 300 mg of Amiodarone intravenously within 2 min, followed in 4 patients by 150 mg after 15 min. All patients were monitored for 1 hour; ECG and blood pressure were recorded at fixed times. Within 15 min sinus rhythm was restored in 88% of PSVT, in 27% of atrial flutter and in 17% of atrial fibrillation cases; the other cases of atrial flutter and fibrillation always showed a 48-81% reduction of the average heart rate within 15 min. We have evidenced neither significant modifications of blood pressure and ECG parameters (P-Q, QRS and Q-T duration) nor particular side effects, except for 2 cases in which brief hot flushes were reported. The Authors believe Amiodarone to be an effective and well tolerated drug for the above mentioned arrhythmias, particularly promptly acting in PSVT cases, in whom sinus rhythm was restored within 15 min in 88% and within 1 hour in 100% of the cases. PMID- 4018469 TI - [Amiodarone by intravenous route]. PMID- 4018470 TI - [Efficacy and duration of action of isosorbide-5-mononitrate in the treatment of stable angina of effort. Comparison with sustained-release isosorbide dinitrate]. AB - A new compound, Isosorbide-5-mononitrate (IS-5-MN; 40 mg orally), was compared with sustained-release Isosorbide dinitrate (SRDI; 40 mg orally) in 18 patients with chronic exercise-induced angina pectoris. The patients were studied in a randomized placebo-controlled single-blind trial. Multistage bicycle test with computer-assisted electrocardiographic analysis was performed before, 60-90, 240 and 360 minutes after treatment administration. Both drugs significantly and comparably prolonged exercise time (p less than 0.01) and time to development of 1 mm ST-segment depression (p less than 0.01) at the 3 times of study. At the highest common level of work, ST-segment depression and its integral were significantly reduced by both IS-5-MN and SRDI compared to placebo (p less than 0.01); conversely, the peak ST-segment depression was unaffected. Compared to placebo, a significant increment in maximal heart rate/systolic blood pressure was observed after drug administration. It is concluded that 40 mg of orally administered IS-5-MN is effective during at least 6 hours and that its therapeutic action is comparable to that of SRDI. PMID- 4018471 TI - [2-dimensional echocardiography in the evaluation of pericardial pathology: new prospects for its differential diagnosis]. AB - We examined retrospectively the M-mode and two-dimensional echocardiograms performed in our laboratory on 227 patients with pericardial diseases, in order to assess the capabilities and limits of echocardiography in this field. We observed 4 patients with congenital absence of the pericardium, 10 with of constrictive or infiltrative-adhesive pericarditis, 213 pericardial effusions, associated with left pleural effusion in 36 cases and with different kinds of intrapericardial masses in 33 cases. Through qualitative analysis of the echogenicity of such masses some aspects were singled out which may prove useful in identifying intrapericardial fat, as well as tumors. We also suggest new ways of using specific echocardiographic sections to differentiate left pleural effusions from pericardial effusions, and to identify very small pericardial effusions. PMID- 4018472 TI - [Aortic coarctation and aneurysms of the ascending aorta]. AB - Dissection and rupture of the aorta account for 20% of death in the natural history of aortic coarctation. We describe here in four patients in whom an ascending aortic aneurysm was associated with aortic coarctation. Three patients had aortic valve incompetence. In two cases there was a dissection. This had not been recognized preoperatively in one, in whom the intimal tear was small; in the other patient, with dissection and shock, the associated mild coarctation was demonstrated only at autopsy. Surgical treatment of patients with aortic coarctation and associated aortic aneurysm must include resection of both the stenotic isthmus and dilated section of the aorta, because of a documented poor prognosis. Furtherly, when evaluating patients with aortic dissection a coexisting coarctation although infrequent must be ruled out. If such an association is identified in emergency cases the dissected aorta should be repaired first, employing a suitable technique (double arterial cannulation, above and below the isthmus) in order to ensure adequate perfusion. When there is no acute dissection, repair of the coarctation should be undertaken first. PMID- 4018473 TI - [External post-infarction rupture of the heart. Retrospective anatomo-clinical analysis of 70 cases]. AB - A retrospective comparison was made between the clinical and pathological findings pertaining to: a) 70 cases of rupture of the ventricular free wall following myocardial infarction (RC group), b) 70 cases of acute myocardial infarction (AMI) where death intervened in the absence of cardiac rupture (NR group) and c) 70 cases (clinical findings only) of patients with AMI admitted to the hospital (IM group). The history of the RC group disclosed a considerably lower percentage of previous myocardial infarctions (p less than 0,005) as compared to the control groups. In the same group systemic hypertension after myocardial infarction was more frequent (p less than 0,025) than in the others. Shock, heart failure, bundle branch blocks were significantly less common in the RC group than in the NR group, and severe arrhythmias were found in a significantly lower percentage than in both the control groups. An electrocardiographic pattern of anterior AMI was more frequent in the RC group than in the IM group (p less than 0,05). Death was preceded by sudden loss of consciousness in 83% of the RC cases and in 51% of the NR cases (p less than 0,005), by severe chest pain respectively in 19% and 9% of the two groups (p less than 0,05). More than 25% of the patients of both RC and NR groups died within the first 24 hours, almost half within the third day after the onset of AMI. On autopsy the AMI was anterior and/or lateral in 77% of the cases in the RC group and in 44% of the NR group (p less than 0,005). In all the cases except one rupture had occurred in the area of the infarction. The site of rupture was anterior in 64% of the cases, posterior in 16%, lateral in 11%, and apical in 9%. Scars larger than 5 mm were noted in 17% of the cases in the RC group as compared to 37% in the NR group (p less than 0,01). Left ventricular hypertrophy was present in 16% of the RC cases and in 31% of the NR group (p less than 0,05). Finally the characteristics of patients at risk of cardiac rupture following myocardial infarction seem to be: absence of previous infarctions, anterior localization of AMI, sustained hypertension after myocardial infarction, absence of serious hemodynamic and arrhythmic complications. PMID- 4018474 TI - [External rupture of the necrotic area in myocardial infarction: resignation or necessity for reexamination?]. PMID- 4018475 TI - [Post-infarction myocardial scars: to cut or not to cut?]. PMID- 4018476 TI - [The surgeon's point of view toward post-infarction scars]. PMID- 4018477 TI - [The cardiologist's point of view toward post-infarction scars]. PMID- 4018478 TI - [Pseudo-aneurysm of the left ventricle. Non-invasive diagnosis of 2 cases]. AB - Left ventricular pseudoaneurysm is a rare condition which may develop after rupture of the ventricular myocardial wall. A localized hemopericardium confined is then formed outlined by the parietal pericardium. The pseudoaneurysmal sac is formed by clots and fibrous pericardial tissue and is directly connected to the ventricular chamber. There are no specific clinical signs to identify the disease. Two dimensional echocardiography and computerized tomography can allow the correct diagnosis to be made before cardiac catheterization. Two cases of left ventricular pseudoaneurysm occurring one after chest trauma and the other after acute myocardial infarction are reported. PMID- 4018479 TI - [Protocol of the serial electropharmacological study for selecting the most efficacious chronic anti-arrhythmia therapy in patients with sustained recurrent ventricular tachycardia and in survivors of cardiac arrest secondary to ventricular tachycardia]. PMID- 4018480 TI - [16th national cardiology meeting of the National Association of Hospital Cardiologists. Florence, 16-19 May 1985. Proceedings]. PMID- 4018481 TI - Gut microflora and small bowel neoplasia: cause or not so innocent coexistence? PMID- 4018482 TI - [Constipation caused by colonic inertia and distal obstruction: electromyographic study]. AB - Colonic motility was evaluated in 15 patients with chronic constipation and 12 healthy subjects by both measuring the transit time of 20 radiopaque markers and recording the colonic myoelectric signals by means of a silastic tube equipped with 4 ring contact electrodes. The tube was introduced by flexible sigmoidoscopy so as the electrodes be located at 50, 40, 30 and 20 cm from the anal verge. Constipation resulted from colonic inertia in 7 patients, the markers being delayed over the whole length of the colon. In the 8 other patients, constipation was due to distal obstruction, the markers accumulating electively in the rectum. The myoelectric tracings showed in the control subjects, on one hand rhythmical stationary spike potentials that occurred at only one electrode site at a mean rate of 10 per minute; on the other hand sporadic (non-rhythmic) spike potentials that were either propagating over the colonic segment (sporadic propagating potentials) or not (sporadic non-propagating potentials). In the constipated patients, the following changes were observed: 1) the number of sporadic propagating potentials was significantly decreased in colonic inertia (2.5 +/- 1.3 bursts of spikes per hour) compared to the controls (8.5 +/- 1.1 bursts/h) or distal obstruction (7.9 +/- 1.3 bursts/h); 2) sporadic propagating potentials usually moved aborally; however, 19.8 +/- 0.9 p. 100 moved orally in colonic obstruction, while 4.6 +/- 0.2 p. 100 in the controls and 4.7 +/- 0.1 p. 100 in colonic inertia.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4018483 TI - [Effect of fundus vagotomy on the gastric emptying of the solids and liquids of a meal in patients with and without postoperative duodenal ulcer recurrence]. AB - The effects of fundic vagotomy (FV) on gastric emptying in the solid and liquid phases of a meal were studied by an isotopic technique in 12 patients with duodenal ulcer. Postoperative results were compared with those obtained in the same subjects before FV and with control values obtained in an identical group of healthy subjects. Early gastric emptying (perprandial) of the two phases of the meal was enhanced by FV but the results failed to reach statistical significance. Gastric emptying of liquids, measured during the 3 h following the end of the meal, was not significantly modified by FV (half-emptying times: 62 +/- 5 min before FV, 75 +/- 8 min after and 65 +/- 7 min for controls). That of solids was significantly delayed by FV (per cent emptied by min: 0.50 +/- 0.02 p. 100 before FV, 0.40 +/- 0.03 p. 100 after, and 0.49 +/- 0.02 p. 100 for controls); this delay was found in all but one patient, but the difference was very slight. Eleven of the 12 investigated patients cured by the operation, were compared with 6 subjects presenting with post FV recurrence: gastric emptying rates of solids (0.41 +/- 0.02 p. 100/min and 0.47 +/- 0.07 p. 100/min) and half emptying times of liquids (72 +/- 10 min and 61 +/- 10 min) were not significantly different. Thus, the gastric emptying rate of an ordinary meal remains practically unchanged by FV and postoperative recurrences of duodenal ulcer cannot be explained by alteration of gastric evacuation. PMID- 4018484 TI - [Histochemical changes of the intestinal mucus in benign and malignant lesions of the colon and rectum]. AB - The purpose of this work was to assess the presence of an abnormal production of sialomucins in different pathological conditions using high iron diamine-Alcian blue staining. Sixty patients with a colorectal tumor and 95 subjects with either a normal colonic mucosa or suffering from non-malignant colorectal disease were studied. An increased production of sialomucins was searched in the first group on the mucosa of the tumor, on the transitional mucosa and on the surgical resection margins respectively and in the second group, on the colonic mucosa. A retrospective study was also performed on 48 patients who underwent curative resection for colorectal tumor. Twenty-four of those patients subsequently developed local tumor recurrence whereas the 24 other patients remained free of recurrence. The prospective study showed the presence of a constantly increased production of sialomucins in the neoplastic mucosa. These abnormalities were found in: 85 p. 100 of cases in the transitional mucosa, in 42 p. 100 and 25 p. 100 of the proximal and distal resection margins respectively, and in 73 p. 100 of patients with dysplasia. The retrospective study showed that 83 p. 100 of patients suffering from local recurrent tumors had an increased production of sialomucins whereas only 8 p. 100 of patients free of local recurrence presented such an abnormal production. This study confirms the presence of an increased production of sialomucins in various pathological colorectal conditions. It suggests that it is possible to individualize a high risk group of patients who might justify a closer follow-up with appropriate therapy. PMID- 4018485 TI - [Hepatotoxic amiodarone?]. PMID- 4018486 TI - [Course of chronic hepatitis related to B virus in children. Study of serum viral DNA]. AB - Nineteen children with chronic hepatitis related to the hepatitis B virus were followed for an average of 6 years. The determination of the hepatitis B virus DNA in the serum allowed us to know the state of viral replication. Thus three groups of patients could be defined: the first in which replication remained active during the total period of follow-up; the second in which the extinction of replication was observed; the third in which replication was inactive from the beginning of the serological follow-up. Symptoms, high levels of aminotransferases and histologically aggressive lesions, sometimes with cirrhosis, were more frequent in the presence of viral DNA. During the decrease of the replication, a clear-cut and time-limited increase of serum aminotransferase levels was often noted. After the disappearance of hepatitis B virus DNA in the serum, clinical signs could be found only in children with cirrhosis or hepatocellular carcinoma. Four cases of hepatitis with initial aggressive lesions led to persistent chronic hepatitis without viral DNA in the serum. In all but one of the patients who started with an aggressive form, viral DNA disappeared in the serum. This loss occurred later and only in 2 patients of 5 who presented initially with chronic persistent hepatitis. Thus a long period of follow-up in childhood chronic hepatitis related to B virus shows frequent inactivation of viral replication. This evolution seemed to occur earlier when the initial histological lesions were aggressive as if this aggressiveness favored the elimination of the virus and the presence of specific antibodies in the serum.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4018487 TI - [Plasmacytoma of the head of the pancreas: a rare cause of cholestatic jaundice]. AB - A case of plasmacytoma of the head of the pancreas in a 75-year-old woman, revealed by obstructive jaundice, is reported. The tumor, which compressed the main bile duct, appeared to be round on sonographic and endoscopic retrograde cholangiographic investigations. Sonographically guided needle biopsy was performed but led to the erroneous diagnosis of pancreatic adenocarcinoma. Choledochojejunostomy and gastrojejunostomy were then performed but the patient died 10 days after the operation. Pathological examination of the specimens obtained at autopsy showed that the pancreatic tumor (as well as an other osseous lesion) were plasmacytomas with cells containing G immunoglobulins of the lambda type. Despite the failure of needle biopsy to lead to correct diagnosis in this case, the potential value of this method remains unequivocal as reported previously. Indeed, when positive results are obtained by this method in visceral localizations of plasmacytoma, hazardous surgery may be avoided and radiation and/or chemotherapy may be chosen preferentially. PMID- 4018488 TI - [Acute hepatopathy caused by amiodarone. Study of a case and review of the literature]. AB - The authors report the case of a non-alcoholic 73-year-old man, treated for arrhythmia with amiodarone for 2 months, and hospitalized because of jaundice and hepatomegaly. There was an important increase in serum alkaline phosphatase activity (4 times the normal value) and a moderate increase in the serum activity of transaminases (3-4 times the normal value). Endoscopic retrograde cholangiography was normal. Serum markers of virus B and tissue antibodies were absent. Histological examination of a liver specimen disclosed portal and periportal fibrosis, mixed inflammatory infiltrate of the portal spaces, and ductular proliferation. Lamellar lysosomal inclusions were demonstrated on electron microscopy. Outcome was favorable after withdrawal of amiodarone. This report, as well as the 7 previously published cases, cannot explain the pathogenesis of amiodarone-induced liver changes. PMID- 4018489 TI - [Gastroesophageal reflux and respiratory manifestations]. PMID- 4018490 TI - [Concentrations of carcinoembryonic antigen and ferritin in pleural and ascitic effusion of various origins]. PMID- 4018491 TI - [Primary biliary cirrhosis: 10 cases followed for 10 years in Israel]. PMID- 4018492 TI - [Hepatotoxicity of sulindac. A new case]. PMID- 4018493 TI - Cimetidine vs a combination of antacid and anticholinergic for hospitalized patients with gastric ulcer. AB - One hundred and eighty-five inpatients with ulcer in the gastric corpus and angle were treated with either 1 g cimetidine per day or with a combination of antacid and anticholinergic. At 2, 4, 6 and 8 weeks after entry into the study, the ulcer had healed in 3.3, 30.4, 55.4 and 87.0 per cent of patients treated with cimetidine, as compared with 0, 12.9, 51.6 and 73.1 per cent of those treated with a combination of antacid and anticholinergic (NS., p less than 0.01, NS., p less than 0.05), respectively. Factors that had a delaying effect on ulcer healing were seen more frequently in the cimetidine group. Thus, cimetidine proved to be superior to a combination of antacid and anticholinergic, for the treatment of gastric ulcer. PMID- 4018494 TI - Hyperglycemia induces intestinal sucrase activity in subtotally pancreatectomized rats. AB - The effects of experimental diabetes, hypertonic glucose infusion, and subsequent insulin administration on the sucrase activity of the small intestine were studied using intestinal segments completely excluded from luminal continuity by construction of Thiry-Vella fistulas in rats. Eight weeks after subtotal pancreatectomy, the rats contracted insulin-deficient diabetes mellitus, and sucrase activity was enhanced in both the Thiry-Vella loop and in the proximal jejunum in continuity. Subcutaneous injections of insulin during the last 4 weeks maintained the enzyme activity in the control range in both segments. There was a positive correlation between sucrase activity and blood glucose level in the pancreatectomized rats. Hyperglycemia in normal rats induced by intravenous infusion of 30% glucose solution over 48 hours enhanced the sucrase activity in the jejunum. Furthermore, insulin administration with a glucose solution inhibited the enhancement of enzyme activity. These findings suggest that hyperglycemia itself might play an important role in the diabetic increment of sucrase activity. PMID- 4018495 TI - Studies on the effect of glucagon on human pancreatic secretion by analysis of endoscopically obtained pure pancreatic juice. AB - The effect of glucagon on human exocrine pancreatic secretion was evaluated in ten patients by analysis of pure pancreatic juice. Pancreatic juice was obtained by endoscopic cannulation of the pancreatic duct at 2-min intervals during constant intravenous infusion of secretin (1 U per kg of body weight per hr) plus caerulein (0.04 micrograms per kg of body weight per hr). Since steady secretion was established 20 minutes after the start of juice collection, a further five 2 min fractions were collected as controls, then constant intravenous infusion of glucagon (15 micrograms per kg of body weight per hr) was commenced. Pancreatic juice was collected for a further 20 minutes. The control fractions and post glucagon fractions were compared in each patient using Student's test. Glucagon depressed secretin-caerulein-stimulated pancreatic secretions. More uniform reductions were observed in the concentration and output of protein and enzymes. Individual variations were observed in the secretory volume and bicarbonate concentration and output. Amylase and lipase were depressed in a parallel fashion in seven patients and in the remaining three, amylase was more depressed than lipase. The post-glucagon reduction in pancreatic secretion was not proportional to the rise in plasma glucagon and blood glucose. PMID- 4018496 TI - Hexose and hexosamine concentrations in human pancreatic juice. AB - Hexose and hexosamine contents were measured in 117 samples of either duodenal or pancreatic juice from 49 subjects. The specimens were obtained by three methods: firstly, through a Dreiling's double lumen tube and with a pancreozymin secretin test performed simultaneously; secondly, by fiber duodenoscopy after an intravenous injection of secretin; thirdly, through a postoperative cannula without stimulation. The hexose content measured by phenol-sulfuric acid reaction correlated well with the hexosamine content measured by the Elson-Morgan method (r = 0.63, p less than 0.005). Since determination of hexose is not as complicated as that of hexosamine, the measurement of hexose content in the pancreatic juice seems to be more useful than measuring hexosamine for obtaining valuable information on pancreatic abnormalities. PMID- 4018497 TI - Motilin: a mechanism incorporating the opossum lower esophageal sphincter into the migrating motor complex. AB - The lower esophageal sphincter (LES) exhibits cyclical phasic contractile activity synchronous with phases II and III of the gastric migrating motor complex. Motilin has been implicated in this process, although the exact mechanism is unknown. The effect of motilin on LES pressure and on gastrointestinal myoelectric activity was examined in 8 unanesthetized opossums. Intraluminal pressure was recorded by a manometric assembly incorporating a sleeve device. Myoelectric activity was recorded from the stomach, duodenum, and jejunum via implanted electrodes. The opossum LES exhibited cyclical periods of phasic contractions synchronous with phases II and III of the gastric migrating motor complex cycle. Variations in the occurrence and magnitude of the phasic LES pressure waves paralleled the spontaneous cyclic fluctuations in the level of circulating plasma motilin. Pulse doses of exogenous motilin (25-400 ng/kg) elicited a contractile LES response that mimicked the spontaneous migrating motor complex-related phasic LES contractions. This effect was dose related with the maximal response occurring at a motilin dose of 100 ng/kg. The LES response to motilin was abolished by hexamethonium and significantly antagonized by atropine and 4-diphenylacetoxy-N-methylpiperidine methiodide, but was not affected by pirenzepine, phentolamine, or naloxone. The study findings support the hypothesis that cyclic increases in circulating endogenous motilin incorporate phasic LES as well as gastric contractile activity into the gastrointestinal migrating motor complex cycle. Motilin acts on the LES by the preganglionic stimulation of cholinergic nerves. PMID- 4018498 TI - Substrate-level energy dependence of acid secretion in the isolated human gastric mucosa. AB - The substrate-level energy dependence of acid secretion was investigated in the human gastric mucosa in vitro using biopsy specimens obtained during fiberoptic gastroscopy in symptomatic patients. The oxygen consumption and the accumulation of aminopyrine were used as indexes of secretory activity. Basal and histamine stimulated oxygen uptake by fundic biopsy specimens were not affected by medications (pethidine and diazepam) administered during gastroscopy. Under substrate-depleted conditions, the oxygen consumption and the aminopyrine accumulation of fundic mucosa were not significantly increased by histamine. Stimulation of functional activities by gastric secretagogues was observed only in the presence of exogenous substrates. The ability of various substrates to support acid formation in the presence of gastric secretagogues was evaluated. Carbohydrates were found to be effective substrates in supporting the functional responses of the tissue, with glucose being the most effective. Propionate, butyrate, beta-hydroxybutyrate, and octanoate were ineffective as substrates. Glucose by itself, but not butyrate, significantly increased oxygen uptake and aminopyrine accumulation. The results suggest that the human gastric mucosa, in vitro, has an absolute requirement for metabolic substrates to support secretory responses and that carbohydrates seem to be the preferential substrates. PMID- 4018499 TI - Control of gastric pH with cimetidine: boluses versus primed infusions. AB - Previous studies suggest that antacids are more effective than intravenous cimetidine in maintaining the gastric pH above 4.0 in acutely ill patients. We hypothesized that this was because blood levels of cimetidine are not sustained at therapeutic levels with the bolus doses. The purpose of this study was to compare gastric pH and serum cimetidine levels when cimetidine was administered as bolus versus infusion. We studied 23 acutely ill patients who received intravenous cimetidine given as boluses and primed infusions. The gastric pH could be maintained above 4.0 with infusions of up to 50 mg/h (1200 mg/day) in 20 patients, compared with only 5 patients with bolus administrations of up to 300 mg every 6 h (1200 mg/day). The differences in ability to maintain the gastric pH above 4.0 were entirely due to the reduced ability of bolus infusion to maintain an adequate serum level. Neither technique could maintain the pH above 4.0 in 3 patients, all of whom had received cimetidine recently. A gastric pH greater than 4.0 correlated directly with a therapeutic serum cimetidine level. We conclude that infusions of cimetidine are better able to sustain therapeutic blood levels and, therefore, are superior to bolus cimetidine in maintaining gastric pH above 4.0. Some patients, however, may not respond to cimetidine even if therapeutic levels are achieved and may require supplemental antacids. PMID- 4018500 TI - Balloon dilatation of upper digestive tract strictures. AB - The results of balloon dilatation of upper digestive tract stricture in 111 patients were evaluated. Eighty-eight patients had esophageal strictures and 23 had gastric or pyloric strictures. Thirty-six patients had strictures associated with previous operations. Twenty-two percent of the patients with esophageal strictures had malignancies. Overall, 92% were successfully dilated, with a complication rate of 3%. Follow-up information was available in 95% of patients. Eighty-seven percent of living patients experienced symptomatic improvement, which lasted for a median period of 12 mo. Forty percent required a further procedure during the period of follow-up. We found no difference between esophageal strictures and gastric or pyloric strictures in success rate, complications, or need for further dilatation, although patients with esophageal strictures were more apt to have symptomatic improvement. Postoperative strictures responded as well as nonoperative strictures. Previously dilated strictures in patients with esophageal reflux were managed as successfully as strictures never before dilated. We found balloon dilatation of upper digestive tract stricture to be a safe, effective technique. PMID- 4018501 TI - Nifedipine: a potent inhibitor of contractions in the body of the human esophagus. Studies in healthy volunteers and patients with the nutcracker esophagus. AB - Nifedipine, a calcium channel blocker, inhibits lower esophageal sphincter pressure but has only minimal effect on esophageal contractions. We investigated the effects of nifedipine on esophageal contractions in 5 healthy volunteers and 10 patients with the nutcracker esophagus. Nifedipine (10, 20, 30 mg) or placebo was ingested as capsules in a double-blind design on 4 separate days. In volunteers, mean distal amplitude decreased 16.6%, 38.4%, and 49.0% as the nifedipine dose was increased. These changes were significantly (p less than 0.05) different from the placebo response and were sustained with higher doses. Patients with the nutcracker esophagus had a similar response, decreasing mean distal amplitude significantly (p less than 0.05) by 16.3%, 36.2%, and 54.2%. In both groups, nifedipine also had a significant (p less than 0.05) dose-dependent depressant effect on distal duration, although to a lesser degree than on amplitude. The percent decrease in distal amplitude showed good correlation (p less than 0.01) with plasma nifedipine concentrations at 60 min. These studies suggest nifedipine may be useful in the treatment of motility disorders of the esophageal body. PMID- 4018502 TI - Effects of morphine and atropine on motility and transit in the human ileum. AB - We examined motility of the ileocecal region, pressures at the ileocecal sphincter, and ileal flow after therapeutic doses of morphine and atropine. Using a factorial design in two cells of 8 (2(3] subjects, drugs were given during fasting and postcibally. Morphine (100 micrograms/kg body wt as a bolus intravenously) and atropine (7 micrograms/kg body wt as a bolus) stimulated migrating bursts of phasic activity (similar to phase III of the migrating motor complex). Morphine initially stimulated ileal flow, but atropine could not be shown to have this effect. Atropine reduced markedly the occurrence of sporadic pressure waves in the ileum, but morphine did not. Whereas atropine delayed mouth to-ileum transit of polyethylene glycol, given in a mixed meal, morphine did not. Naloxone, in the dosage used (40 micrograms/kg body wt as a bolus, followed by 10 micrograms/kg body wt X h) had no independent effects on motility or flow, but did blunt the stimulatory effects of morphine and atropine on migrating motor complexes. We could not demonstrate an effect of any drug on the transit of lactulose from terminal ileum to cecum. Neither morphine nor atropine had impressive effects on tone at the ileocecal sphincter. These observations, while not specifying the mechanisms for constipation after opiates or anticholinergics, highlight the complexities of small bowel transit in humans and point out that the antidiarrheal effects of drugs are probably multifactorial. PMID- 4018503 TI - Active and inactive replication of hepatitis B virus deoxyribonucleic acid in chronic liver disease. AB - Little is known about the replicative forms of hepatitis B virus (HBV) in the liver in chronic liver disease. We therefore analyzed HBV DNA and the changes in DNA signals after endonuclease digestion in liver tissues taken from 64 patients with hepatitis B surface antigen-positive chronic liver disease. The "active" replication pattern, which included various replicative intermediates, was seen in 36 of 38 (95%) hepatitis B e antigen-seropositive patients. This pattern was also found in 5 of 26 (19%) hepatitis B e antigen-seronegative patients who showed the highest mean serum alanine aminotransferase level (403 +/- 184 mU/ml). Most of them had advanced liver disease. Episomal viral DNA of an "inactive" type having only the supercoiled form was found in 3 patients; they showed the lowest mean serum alanine aminotransferase level (27 +/- 7 mU/ml) and only mild liver disease. As with duck HBV infection, episomal replicative forms of human HBV could be resolved by Southern blot analysis and seem to have clinical implications in human HBV infection. PMID- 4018504 TI - Metabolism of lithocholic and chenodeoxycholic acids in the squirrel monkey. AB - Metabolism of lithocholic acid (LCA) and chenodeoxycholic acid (CDCA) was studied in the squirrel monkey to clarify the mechanism of the lack of toxicity of CDCA in this animal. Radioactive LCA was administered to squirrel monkeys with biliary fistula. Most radioactivity was excreted in the bile in the form of unsulfated lithocholyltaurine. The squirrel monkey thus differs from humans and chimpanzees, which efficiently sulfate LCA, and is similar to the rhesus monkey and baboon in that LCA is poorly sulfated. When labeled CDCA was orally administered to squirrel monkeys, less than 20% of the dosed radioactivity was recovered as LCA and its further metabolites in feces over 3 days, indicating that bacterial metabolism of CDCA into LCA is strikingly less than in other animals and in humans. It therefore appears that LCA, known as a hepatotoxic secondary bile acid, is not accumulated in the squirrel monkey, not because of its rapid turnover through sulfation, but because of the low order of its production. PMID- 4018505 TI - Effect of mucous glycoprotein on nucleation time of human bile. AB - The purpose of this study was to determine whether mucous glycoprotein is the nucleating factor responsible for the rapid in vitro nucleation time of gallbladder bile from persons with cholesterol gallstones. Ultracentrifugation and ultrafiltration of abnormal bile removed all detectable mucous glycoprotein, yet bile that had been filtered exhibited as rapid a nucleation time as unfiltered bile. When abnormal bile was heated to 95 degrees C for 60 min, nucleation time was significantly prolonged. Rapid nucleation time could be restored to heated abnormal bile by addition of small volumes of unheated bile. Purified human mucous glycoprotein accelerated nucleation time of human bile, but mucous glycoprotein from control patients was as effective as that from gallstone patients. There was a direct relationship between mucous glycoprotein concentration and effect on nucleation time. Mucous glycoprotein may be important in the early stages of stone formation, but it is probably not the agent responsible for the sharp discrimination between control bile and gallbladder bile from patients with cholesterol stones found in the in vitro nucleation time test. The markedly prolonged nucleation time of heated abnormal bile is preliminary evidence that the nucleating factor may be a heat-labile protein other than mucous glycoprotein. PMID- 4018506 TI - Chylomicronemia induced by cimetidine. AB - A 35-yr-old man with moderate hypertriglyceridemia, associated with a positive family history for hyperlipidemia, developed chylomicronemia with abdominal pain, muscle pain, and splenomegaly while being treated with cimetidine for a duodenal ulcer. The chylomicronemia and the pain subsided after the drug was stopped. When the patient was rechallenged with the drug 6 mo later, the chylomicronemia reappeared after a treatment period of 6 days. Chylomicronemia and its complications should therefore be considered as a potential risk when cimetidine is prescribed to patients with known hyperlipidemia. PMID- 4018507 TI - Revised classification of pancreatitis. Report of the Second International Symposium on the Classification of Pancreatitis in Marseille, France, March 28 30, 1984. PMID- 4018509 TI - A vascular cause of Hirschsprung's disease? PMID- 4018508 TI - Presence of hepatitis B virus-deoxyribonucleic acid in human tissues under unexpected circumstances. PMID- 4018510 TI - 5-aminosalicylic acid for the treatment of inflammatory bowel diseases. PMID- 4018511 TI - Roux-en-Y syndrome. PMID- 4018512 TI - Occult blood in colorectal cancer. PMID- 4018513 TI - [Problems of pregnancy and labor in drug addicts]. AB - Obstetrical problems during pregnancy and labor of drug-dependent female patients. Drug-abuse during pregnancy constitutes an increase of risks as well to the pregnant woman and the fetus as to the mother and to the newborn. In a retrospective study the problems of antenatal care and therapy and the effect on the fetal outcome are discussed. PMID- 4018514 TI - [Comparison between the radioimmunologic measurement of plasma E2 and estrogen determination in urine using a hemagglutination inhibition test]. AB - To prove the diagnostic value of a new haemagglutination inhibition test (HI Estrotec), urinary and plasma oestrogens were simultaneously measured in 42 stimulated cycles of 40 women of the Erlangen IVF programme. Comparing the results of all paired samples, there was a correlation coefficient r = 0.6968. Correlating the total oestrogens in the early morning urine with the plasma-E2, the coefficient was r = 0.641. In 26 cases of the 42 stimulated cycles egg retrieval could be performed. Averaging the daily values of these women the graphs of E2 and urinary oestrogens show nearly parallel curves with maximal values on the same day, i.e. the first day after HCG application. Comparing the two curves of the individual patient, in 14 of 26 cases there are differences of more than 24 hours between the maximal values of urinary and plasma oestrogens. The advantages of the HI-Estrotec-Assay are: Simple handling without special demands on the laboratory equipment. The results can be obtained after two hours already. The possibility to measure several times a day without great effort. The disadvantage is: The delayed appearance of the hormones in the urine. To induce ovulation with HCG, however, actual parameters are indispensable. If the ovulation is triggered by the endogenous LH surge the diagnostic value of the new assay is sufficient when it is combined with an LH monitoring. PMID- 4018515 TI - [In-vitro-fertilization: chromosome analysis of unfertilized human oocytes]. AB - Chromosomal abnormalities and abnormal embryonic development have been observed after human in vitro fertilisation (IVF). Such investigations are not permitted according to the ethical guidelines approved by the IVF team in Berlin ("Berliner Modell"). However, the chromosomal status was studied in oocytes which remained unfertilised in a human IVF programme. In 50 fertilisation attempts the chromosomes of 62 oocytes could be analysed. 45 of the oocytes were in the process of meiotic maturation. One of these showed abnormalities in the first meiotic division and seven during the second meiotic division. After fertilisation in addition to normal embryos, all of which were transferred to the mother, three embryos were triploid and six oocytes were fragmented. The results prove that in human IVF chromosome abnormalities can occur in oocytes already before fertilisation. The importance of the results for later stages of embryonic development is discussed. PMID- 4018516 TI - [Corporofundal partial peripheral bladder denervation as surgical therapy of urge incontinence]. AB - Urge incontinence places a considerable burden on incontinence treatment. The autonomous nerve supply of the bladder is effected via two anatomically clearly separate ways. On the one hand, we have the accessory innervation via the fascia endopelvina, whereas on the other hand fibres from the plexus pelvicus as the classical site of innervation penetrate into the bladder. Transection of the fascia endopelvina followed by detachment of the plexus pelvicus from the lateral bladder wall in the course of separation of the bladder and levator enables corporofundal partial peripheral bladder denervation. By this procedure both afferent and efferent nerve fibres are transected. As a result, excess autonomous impulses are reduced, thus effecting favourable reduction of the urge incontinence pattern. This method is quite fascinating not only because it is easily translated into practice, offers ideal vaginal access, and is reproducible at all times, but also because it can be utilised as a therapeutic tool in the treatment of urge incontinence, and because it can be integrated in an optimal manner into the standard incontinence and descensus programme. A failure rate of 3% is hardly ever exceeded. Compared with the other methods described so far, which are mostly very severe in their effect and highly specialised, the advantages of corporofundal partial peripheral bladder denervation point towards considerable chances to translate the method into practical reality. PMID- 4018517 TI - [Chlamydia trachomatis--studies on the reliability of its detection in Papanicolaou preparations]. AB - In a matched group of 104 chlamydia culture-positive and 104 culture-negative women, the correlation between simultaneous cultures and cytological findings in the Papanicolaou smear was studied. Cellular changes in metaplastic cells that are described in the literature as being specific for Chlamydia trachomatis, were not associated with genital chlamydial infection. In particular the reported high sensitivity of intracytoplasmatic inclusion bodies could not be confirmed. Likewise, even severe inflammatory changes and a high concentration of lymphocytes were also no reliable diagnostic indicator. The authors conclude that the Papanicolaou smear is not useful as a routine screening method for genital chlamydial infection. PMID- 4018518 TI - [Solitary neurofibroma of the lumbosacral plexus. Case report]. AB - The article describes a case of a solitary neurofibroma of the plexus lumbosacralis causing pain and incomplete leg paresis. Complete relief was obtained by total extirpation of the tumour, a procedure which must be regarded as the method of choice. Pain and pareses in the lower extremities require differential diagnostic consideration of rare neurogenic tumours of the peripheral nervous system in the regions of the pelvis and plexus lumbosacralis. Neurological examination by a specialist is of significant importance preoperatively to determine the seat of the tumour and to assess the postoperative course. PMID- 4018519 TI - [Normalization of the physico-chemical properties of blood by hemosorption after its long-term preservation]. PMID- 4018520 TI - [Viability of autologous and donor erythrocytes after different periods of preservation in patients with burns during acute toxemia and septicemia]. PMID- 4018521 TI - [Detoxication of the body by direct replacement of blood in extensive burns]. PMID- 4018522 TI - [Relation between erythrocyte resistance and antioxidative enzyme activity]. PMID- 4018523 TI - [Functional state of erythrocytes in persons engaging in healthful running]. PMID- 4018524 TI - [Fibronectin of blood plasma]. PMID- 4018525 TI - [A continuous action blood fractionator]. PMID- 4018526 TI - ["Preleukemia": clinico-laboratory characteristics of 28 patients]. PMID- 4018527 TI - [Disorders of karyotype of hematopoietic cells in preleukemic states]. PMID- 4018528 TI - [Disputable problems of classification of malignant lymphoproliferative diseases]. PMID- 4018529 TI - [Immunity factors and nonspecific anti-infection defense in hairy cell leukemia]. PMID- 4018530 TI - [Characteristics of the metabolism of erythrocytes in pregnant women with anemia]. PMID- 4018531 TI - [Immunologic status of children after splenectomy in trauma]. PMID- 4018532 TI - [Effect of repeated administration of dexamethasone on various indicators of erythropoiesis]. PMID- 4018533 TI - [Preleukemia]. PMID- 4018534 TI - The binding of isocyanides to cytochrome P-450 from mouse hepatic microsomes. AB - The spectral interactions of a number of isocyanides with cytochrome P-450 were investigated. An interaction between the hydrophobic nature of the side chain and the spectral interaction was apparent. The concentration of the isocyanide affected the stability of the complex. Phenyl isocyanide dichloride was determined to be an acceptable replacement for ethyl isocyanide for the characterization of cytochrome P-450. PMID- 4018536 TI - Effects of calcium antagonists on smooth muscle membranes of the canine stomach. AB - In circular muscles of the canine stomach, diltiazem (greater than 3 X 10(-6)M) depolarized and nicardipine (greater than 10(-6)M) hyperpolarized the membrane. Diltiazem (greater than 5 X 10(-6)M) or nicardipine (greater than 3 X 10(-7M) inhibited the plateau potential of spontaneously generated or electrically evoked action potential. In Na-deficient solution (between 137 and 30 mM Na), diltiazem and nicardipine selectively inhibited the plateau potential. In Na- (15 mM Na) or Ca-deficient (0.25 mM Ca) solution, spontaneously generated action potential ceased, and only graded responses were evoked by electrical stimulation. These graded responses were inhibited by diltiazem (greater than 5 X 10(-6)M) or nicardipine (greater than 3 X 10(-7)M). The ionic contribution for generation of action potential in this muscle cell was discussed in relation to actions of Ca antagonists. PMID- 4018535 TI - Spectral interactions of piperonyl butoxide and isocyanides with purified hepatic cytochrome P-450 from uninduced mice. AB - The binding of isocyanides and the metabolites of piperonyl butoxide (PBO) to reduced cytochrome P-450 in intact microsomes gives rise to the type III optical difference spectrum which is characterized by two pH dependent peaks in the Soret region. Each of the purified cytochrome P-450 isozymes (A1, B1, B2, B3) metabolized PBO and produced a spectrum in the Soret region. Only the A1 fraction produced the pH dependent type III spectrum. The B1 fraction produced a spectrum with only one peak at 430 nm while the spectrum produced by both the B2 and B3 fractions contained only the 455 nm peak. Each of the isozymes produce pH dependent type III spectra with both ethyl isocyanide and phenyl isocyanide dichloride. PMID- 4018537 TI - Effect of adenosine 5'triphosphate (ATP) on the isolated rectum of the rainbow lizard Agama agama. AB - ATP but not adenosine contracts lizard isolated rectal muscles. Theophylline, quinidine, nifedipine and lack of Ca2+ inhibited ATP contractions, but dipyridamole, indomethacin, atropine, D-tubocurarine, phentolamine, L propranolol, cimetidine, mepyramine and methysergide did not significantly modify the contractions. ATP inhibited Ca2+-induced contractions in Na+-free, high K+ media. In normal Ringer, it relaxed carbachol-contracted muscles and inhibited KCl contractions. The results suggest that ATP contractions are dependent upon external Ca2+, and are probably associated with extracellular Ca+ influx. The contractions appear to have occurred independently of receptor activation and may have been mediated by a depolarising action of the nucleotide. The relaxant effect of ATP possibly occurred as a consequence of inhibition of Ca2+ influx into carbachol or K+-depolarised muscles. PMID- 4018538 TI - Evidence for multiple sources of calcium involved on the contractile effects of agonists in the dog uterus. Influence of ovarian sexual hormones. AB - We compared the characteristics of Ca2+ pools involved in the contractile effect of acetylcholine (Ach), histamine (Hist), oxytocin (Oxy) and barium (Ba2+) in prepuberal untreated or estrogen plus progesterone dominated uteri. After Ca2+ (0.2 mM) withdrawal different rates of decay for cited agonists were observed. If Ca2+ concentration was increased to 2.0 mM before the Ca2+ withdrawal, the t 1/2 for Ach and Hist were markedly increased. Hormonal treatment significantly increase the rate of decay for all agonists except for Ba2+ independent of the initial Ca2+ concentration, suggesting that in this condition the tightly bound Ca2+ is absent. PMID- 4018539 TI - Effect of tetraethylammonium and verapamil on noradrenaline release induced by field electrical stimulation and potassium from cat cerebral and femoral arteries. AB - Tritium release evoked by field electrical stimulation (FES) or high potassium (K+) from cat cerebral and femoral arteries prelabelled with 3H-noradrenaline was investigated. The release induced by FES and K+ was reduced by Ca2+ suppression and tetrodotoxin (TTX) but not by verapamil in both vessels. Tetraethylammonium (TEA) increased tritium release evoked by FES and K+, when TTX plus TEA were added together radioactivity secretion induced by FES was practically abolished. These results indicate that FES or K+ induce exocytotic noradrenaline release mainly by propagated action potentials and by similar mechanisms in cerebral and femoral arteries. PMID- 4018540 TI - Dose-related effects of fentanyl on autonomic and behavioral responses in performance horses. AB - The dose-related effects of intravenously administered fentanyl (0.010, 0.005, 0.0025 mg/kg) and saline were studied in mature performance horses using a rigorous experimental protocol. Fentanyl produced a dose-related prolongation of the skin twitch reflex latency but did not increase the hoof withdrawal reflex latency. Dose related increases in stepping frequency, cardiac and respiratory rats were observed following fentanyl, while changes in rectal temperature and pupil area were not. These data indicate that fentanyl, a prototypic mu-agonist, produces a syndrome characterized by analgesia, locomotor and sympathetic stimulation in the horse. PMID- 4018541 TI - Interaction of muscarinic drugs with their receptor. AB - Interaction of muscarinic drugs with their receptor was studied in the logitudinal muscle of guinea pig ileum. The pD2-value, the index for agonistic activity of a partial agonist was practically equal to its pA2-value, the index for competitive antagonistic activity and to its pKA-value which was a negative logarithm of a dissociation constant (KA), suggesting that the muscarinic drugs such as full and partial agonists and a competitive antagonist interacted with one binding site in the muscarinic receptor. Effects of a GTP-analogue, Gpp(NH)p (guanyl-5'-y limidodiphosphate) decreased affinities of full and partial agonists to the muscarinic receptor in a manner that was correlated with their efficacies. A relationship between the Hill's coefficients of the muscarinic drugs and their efficacies suggest that the ability to distinguish the agonist binding sites was related to their efficacy. PMID- 4018542 TI - Concentrations of ampicillin and cefadroxil in human serum and mixed saliva following a single oral administration of talampicillin and cefadroxil, and relationships between serum and mixed saliva concentrations. AB - The concentrations of ampicillin (ABPC) from talampicillin (TAPC) and cefadroxil (CDX) in serum and mixed saliva were assayed by the thin layer disc plate method. Talampicillin and cefadroxil (500 mg) were given by a single oral administration. The relationships between serum and mixed saliva ampicillin and cefadroxil concentrations were evaluated in the paired specimens collected from 10 different persons, respectively. The means of concentration ratios of mixed saliva to serum ampicillin and cefadroxil were 0.006 +/- 0.003 and 0.025 +/- 0.010 (mean +/- SD), respectively. Significant correlation coefficients between mixed saliva and serum concentrations were found for both ampicillin and cefadroxil, which were r = 0.78, P less than 0.001, and r = 0.67, P less than 0.001, respectively. PMID- 4018543 TI - Pharmacokinetics of human lymphoblastoid interferon in rabbits. AB - By intravenous (bolus) administration of large amounts (29 Mega Units) of lymphoblastoid interferon into rabbits, it has been possible to detect circulating antiviral activity (0.02% of the dose) up to 18 hr post-injection and to determine for the first time the pharmacokinetic parameters. The slow component (elimination phase) has a half-life of 235 +/- 9 min. The total apparent volume of distribution is 2,564 +/- 1,497 ml which is far larger than the combined plasma-extracellular volumes. This suggests a IFN dilution due to its extensive binding to cell receptors. The clearance of 7.3 +/- 4.1 ml/min is an index of the rate of renal and cellular (internalization of the receptor ligand complex) catabolism of IFN. Pharmacokinetic parameters are useful for devising an administration schedule of IFN as an antiproliferative agent but are not predictive of an immunological response if IFN is used as an immuno-adjuvant. PMID- 4018544 TI - A possible explanation for a greater discrepant suppression by adenosine and N6 cyclohexyl adenosine of the guinea-pig ileal contraction. AB - Adenosine and N6-cyclohexyl adenosine (CHA) reduced dose-dependently a twitch contraction of guinea-pig ileum and their IC50 values were 1.0 X 10(-5) and 1.1 X 10(-8) M, respectively. By exposure to adenosine uptake and deaminase inhibitors, dipyridamole and erythro-9-(2-hydroxy-3-nonyl) adenine (EHNA), the adenosine induced inhibition was enhanced, whereas the CHA-induced one was almost unchanged. Therefore, outstanding potency difference of the suppression by adenosine and CHA was minimized by concurrent addition of both the inhibitors. Uptakes of [3H]CHA into the guinea-pig ileum and taenia-coli were considerably lower than those of [3H]adenosine and were insensitive to dipyridamole. In the rat connective tissue segment, uptake of [3H]adenosine was smaller than that in the guinea-pig taenia-coli and ileal segments (especially, in the latter), and was virtually unaffected by 10(-5) M dipyridamole. These findings suggest that a greater discrepancy of the suppression by adenosine and CHA of the ileal twitch may substantially result from their different uptake and deamination in the synaptic region rather than their dissimilar intrinsic activity for the purinoceptor. PMID- 4018545 TI - Influence of antioxidants and radical scavengers on ethanol-induced gastric ulcers in the rat. AB - Sodium benzoate in doses which do not possess antisecretory properties, produced a dose-dependent reduction of ethanol-induced gastric lesions in the rat. Indomethacin pretreatment antagonized sodium benzoate-ulcer reducing properties indicating that this latter acts, at least in part, through stimulation of prostaglandins synthesis. Propyl gallate reduced ethanol-induced gastric lesions in doses which exert antisecretory properties. PMID- 4018546 TI - Zinc sulphate reduces activity-stress gastric lesions in rats. AB - Daily i.p. injections of zinc sulphate significantly reduced the frequency and severity of activity-stress gastric lesions in rats in a dose-related fashion. These lesions are believed to be of a non-acid etiology and respond primarily to centrally-acting agents. The present results suggest that some local factors contribute to activity-stress gastric damage. PMID- 4018547 TI - A quantitative morphological study of the effects of carbenoxolone sodium on duodenal goblet-cells of the rat. AB - A direct microscopic and microdensitometric examination was carried out on duodenal goblet-cells of non-fasted and fasted rats with and without carbenoxolone sodium treatment. The results of microdensitometric examination revealed a marked and significant increase of mucus production in the non-fasted and fasted rats pretreated for 2 hr with a single oral dose of carbenoxolone sodium at 100 mg/kg. Fasting alone also increased mucus production. On microscopic examination, the number of duodenal goblet-cells full of mucosubstances in the non-fasted and fasted rats receiving carbenoxolone sodium treatment was approximately 20% higher than in the controls. PMID- 4018548 TI - Differential alterations in brain sensitivity to amphetamine and pentylenetetrazol in socially deprived mice. AB - Mice deprived of social interactions for different periods of time (56, 69, 79, 89 or 97 days) were studied. Social isolation increased both general activity observed in an open-field and amphetamine-induced hyperactivity; CNS responsiveness to pentylenetetrazol-induced convulsions, however, decreased. The differences in general activity were detected after 69 and 79 days of social deprivation; the hyperactivity induced by amphetamine was greater after 79 days of isolation and the pentylenetetrazol CD50's were higher after 56, 69 and 79 days of solitude. These data, obtained with mice, show first that isolation time is an important variable to display drug effects and secondly that long-term deprivation of social stimuli does not increase CNS susceptibility to all stimulant drugs. A combination of a higher release of catecholamines onto previously supersensitive receptors was considered to be involved with the differences observed. PMID- 4018549 TI - Biosynthesis of ecdysteroids from cholesterol by crab Y-organs, and eyestalk suppression of cholesterol uptake and secretory activity, in vitro. AB - Precursor incorporation studies were conducted in vitro with activated Y-organs from 48-hr de-eyestalked Cancer antennarius donors. When the glands were prelabeled in vivo by systemic injection of [3H]cholesterol 12 hr prior to removal, and subsequently incubated 24 hr in label-free medium, the glands secreted 3H-labeled ecdysone. The glands also secreted an unidentified ecdysteroid with comigrating 3H-label with characteristic retention time on normal-phase HPLC of 4 min (4-min unknown). The compound is less polar, and is secreted in a quantity and apparent specific activity approximately fivefold greater, than ecdysone. Compared with chromatographic retention times and competitive binding curves of authentic standards, the 4-min unknown was determined not to be ponasterone A, inokosterone, makisterone, or several other possible products or intermediates. In contrast with Y-organs from intact donors, those from de-eyestalked crabs exhibit greatly increased cholesterol uptake and secretion of both ecdysone and 4-min unknown in vitro. All three responses were suppressed in dose-dependent manner by eyestalk extract in the dose range, 1-4 eyestalk equivalents/Y-organ. Secretion of 4-min unknown was the response most sensitive to eyestalk extract (requiring the least dose for 50% inhibition). PMID- 4018550 TI - Immunoelectron microscopic localization of growth hormone in the pituitary glands of two teleosts, tilapia (Sarotherodon mossambicus) and amago salmon (Oncorhynchus rhodurus). AB - Growth hormone (GH) cells were investigated with the protein A-gold technique on the pituitary glands of tilapia (Sarotherodon mossambicus) and amago salmon (Oncorhynchus rhodurus). By the use of specific antiserum against tilapia GH to both species, the immunoreactive gold particles were demonstrated to be preferentially located on the secretory granules of the GH cells. Specimens fixed only with periodate-lysine-paraformaldehyde (PLP) preserved the hormonal antigenicity well. Osmium postfixation, although considerably reducing the antigenicity and thus resulting in a decrease in number of the gold particles on the GH cells, gave much more satisfactory ultrastructural preservation and immunoreactive localization of immunoreactive material. This investigation demonstrated that, after combined fixation with PLP and PLP-osmium, we could determine the function of a given cell type in various endocrine organs as well as the precise antigenic sites in such cells. PMID- 4018551 TI - Seasonal changes in the testes and accessory reproductive organs and seasonal and circadian changes in plasma testosterone concentrations in the male grey squirrel (Sciurus carolinensis). AB - A 27-month study of cycles of regression and recrudescence of testis function in adult, grey squirrels in a natural environment in southern England has shown concomitant variation in mean testes weights, mean plasma testosterone concentrations, and mean weights of accessory sex organs, this variation being closely associated with months of the year. Testis regression occurred in the period June to August, the exact timing differing among individuals. In 1979-1980 the testes of all squirrels then remained regressed for 7 months, whereas in the autumn of 1980 testes were regressed in most squirrels for 4 months. There was also evidence of testis regression in some individuals in March 1979 and March 1981. Males born and housed in a small woodland enclosure in 1979-1980 and well fed with grain did not experience the long period of regressed testes. Plasma testosterone concentrations measured hourly over 24 hr in squirrels with large, active testes varied from 0.4 to 20 nmol/l, both within and between individuals, the higher concentrations being observed between midday and midnight. The range in the age of males at puberty, based on fusion of the epiphyses of the wrist, was 1.0 to 1.25 year. Juvenile males housed in a woodland enclosure together with adult males and females remained prepubertal up to 2 years of age. PMID- 4018552 TI - Morphological changes in the ovary of newly hatched chickens treated with chorionic gonadotropin during embryonic development. AB - The present study describes morphological changes produced in the ovary of newly hatched chickens by treatment with human chorionic gonadotropin (hCG). Morphometric measurements of the volume of steroidogenic cells and structures of the ovarian medulla were performed in controls and experimental chickens treated with hCG (1.0 IU/embryo) at 13, 15, and 17 days of embryonic development. After hCG treatment, the volume of interstitial cell cords increased, and modifications in poorly differentiated cells neighbouring the interstitial cells were also observed. Other changes obtained after hCG treatment were an increment in the development of the lacunar system and blood capillaries, as well as a reduction in the number of germ cells in the stroma of the ovarian medulla. PMID- 4018553 TI - Involvement of gonadotrophin and steroid hormones in spermiation in the amago salmon, Oncorhynchus rhodurus, and goldfish, Carassius auratus. AB - Effects of intraperitoneal injections of chum salmon gonadotrophin (SGA) and various steroid hormones (17 alpha, 20 beta-dihydroxy-4-pregnen-3-one; 17 alpha,20 beta-diOHprog, 17 alpha-hydroxy-progesterone, testosterone, 11 ketotestosterone) on the induction of in vivo spermiation were examined in nonspermiating amago salmon (Oncorhynchus rhodurus) and goldfish (Carassius auratus). A single injection of SGA to amago salmon and two successive injections to goldfish induced strong spermiation responses. Similarly two successive injections of 17 alpha,20 beta-diOHprog caused precocious spermiation in both species; however, the response to 17 alpha,20 beta-diOHprog was of lesser magnitude than that to SGA. The spermiation response of goldfish to 17 alpha hydroxyprogesterone was similar to that of 17 alpha,20 beta-diOHprog. Neither testosterone nor 11-ketotestosterone were effective in inducing spermiation in amago salmon, but these steroids were found to be slightly effective in goldfish. Effects of a single injection of SGA on changes in serum levels of 17 alpha,20 beta-diOHprog and 11-ketotestosterone were also examined in nonspermiating amago salmon. Serum levels of 17 alpha,20 beta-diOHprog dramatically increased after treatment and peaked on Day 2 and thereafter declined quickly. Similarly, 11 ketotestosterone peaked on Day 2, but the levels remained high throughout the experimental period. Considered together, these findings are consistent with the suggestion that 17 alpha, 20 beta-diOHprog is involved in the process of spermiation in teleosts. It is further suggested that this hormone is a testicular steroidal mediator of gonadotrophin-induced spermiation in amago salmon. PMID- 4018554 TI - A profile of the intestinal mucosal corticosteroid receptors in the domestic duck. AB - The corticosteroid receptor profile of the intestinal tract of the domestic duck (maintained on either a low-sodium (LS) or a high-sodium (HS) diet) was investigated. Using tritiated triamcinolone acetonide (TA), corticosterone, or aldosterone as ligands, cytoplasmic mineralocorticoid receptors (MR, type I) and glucocorticoid receptors (GR, type II) were found in the mucosal cytosol of the jejunum and colon with the following binding parameters: LS jejunum GR-Kd, 3.4 nM; Nmax, 245 fmol/mg protein; MR-Kd, 0.54 nM; Nmax, 35 fmol/ mg protein; colon GR-3.2 nM; Nmax, 531 fmol/mg protein; MR-Kd, 0.55 nM; Nmax, 113 fmol/mg protein; HS jejunum GR--Kd, 3.2 nM; Nmax, 531 fmol/mg protein; MR--Kd, 0.30 nM; Nmax, 50 fmol/mg protein; colon GR--Kd, 1.1 nM; Nmax, 572 fmol/mg protein; MR--Kd, 0.68 nM; Nmax, 221 fmol/mg protein. The diet little influenced the GR binding parameters, while the MR (aldosterone) binding parameters showed a down regulation following LS (high circulating aldosterone) diets. The competition hierarchy of radioinert steroids on the formation of the [3H]corticosterone receptor complex was corticosterone = cortisol = 11-deoxycorticosterone greater than aldosterone = TA = dexamethasone much greater than 11-deoxycortisol; with [3H]aldosterone, the competition was corticosterone = progesterone = 11 deoxycorticosterone greater than aldosterone = cortisol = TA = dexamethasone greater than 11-deoxycortisol greater than 11-dehydrocorticosterone. The intestinal mucosal receptor was deactivated following treatment with trypsin. On linear sucrose gradients, receptor-ligand complexes sedimented with a single peak at 8.5 S (hypotonic gradient) and 4.0-4.5 S (hypertonic gradient), respectively. Heat-activated [3H]TA- and [3H]aldosterone-receptor complexes bound avidly to DNA cellulose and, upon ion-exchange chromatography on DEAE-Sephacel, the presence of the negatively charged unactivated and the more positively charged activated complexes could be shown. The hydrodynamic parameters, determined by gel filtration chromatography, gave for all three ligand-receptor complexes molecular weight values from 334,000 to 351,000 and Stokes radii from 76.8 to 80.0 A. From these studies it was concluded that the duck intestinal tract possesses vertebrate-type GR and MR, though these receptors were much less specific than their mammalian counterparts. The duck intestinal corticosteroid receptor was found to be different from those of the teleost fish and anuran amphibian, establishing the possibility of a biochemical evolution in nonmammalian intestinal corticosteroid receptor conformation. PMID- 4018555 TI - Sensitivity and specificity of salamandrid integumental transepithelial potential to prolactin. AB - The effects of ovine prolactin (oPRL), bovine growth hormone (bGH) and human placental lactogen (hPL) on in vivo integumental transepithelial potential (TEP) were examined in two salamandrid urodeles, adult terrestrial-phase Taricha granulosa and the juvenile red-eft stage of Notophthalmus viridescens. TEP in efts treated with 1.0 microgram oPRL/2 days fell from 73.3 +/- 6.1 to 15.2 +/- 5.5 mV by Day 7 (P less than 0.001), whereas the TEP of efts treated with either 1.0 or 10 micrograms bGH/2 days remained at control levels for as long as 24 days. TEP in efts treated with a single dose of 10 micrograms oPRL dropped from 65.74 +/- 4.1 to 23.0 +/- 3.4 mV (P less than 0.01) in 3 days. Efts treated with various doses of oPRL showed a linear log total dose response over the range of 0.05 to 10.0 micrograms oPRL/animal, with a minimum detectable total dose of 0.4 micrograms/g (0.01 IU/g). In the same experiments, tail height increased by Day 7 in efts treated every other day with 10.0 micrograms oPRL, but not 1.0 microgram oPRL or either 1.0 or 10.0 micrograms bGH/2 days. In Oregon newts injected every other day with 10 micrograms oPRL, TEP decreased by 33% in 8 days (P less than 0.05), whereas in animals treated with 10 micrograms bGH/2 days, TEP did not change from control values even after 23 days. TEP in Oregon newts receiving a single dose of 100 micrograms oPRL dropped to 68% of initial values within 2 days (P less than 0.05), but subsequently recovered to control values 3 weeks after the last injection.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4018556 TI - Effects of dietary thyroid hormones on growth, plasma T3 and T4, and growth hormone in normal and hypothyroid chickens. AB - Cockerels and pullets fed with T3 or T4 for 2 weeks showed a decrease in both body weight gain and feed efficiency. The reduction in body weight gain and feed efficiency was dose related in cockerels where T3 or T4 were fed at 0.1, 1.0, and 10.0 ppm levels. T3 and T4 at 0.1 and 1.0 ppm had no significant effects on growth or feed efficiency in pullets, but the 10.0-ppm level of T3 and T4 caused a reduction of -55.24 and -28.18%, respectively, in body weight gain as compared with control birds. T3 was more active than T4 in reducing growth and was toxic when fed at 10.0 ppm both in cockerels and pullets. Both propylthiouracil (PTU)- and methimazole-treated cockerels showed a decrease in rates of gain. T3 and T4 at a dietary level of 0.1 ppm were equipotent in promoting growth in these PTU- and methimazole-treated cockerels, but 10.0 ppm caused a further reduction in body weight gain. Plasma T3 levels were found to be significantly higher in birds that were fed either T3 or T4. Plasma T4 levels were higher in T4-fed birds, but significantly lower in T3-fed birds as compared with controls. Both PTU- and methimazole-treated cockerels had significantly lower plasma T3 and T4 concentrations, but elevated plasma GH concentrations. Dietary T3 and T4 at 1.0 and 10.0 ppm significantly lowered plasma GH concentrations. In summary, these results indicated that T3 was more active than T4 in reducing body weight gain in intact normal birds, but that they were equally potent in promoting growth in PTU and methimazole-treated hypothyroid birds.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4018557 TI - The in vitro metabolism of radioactive progesterone and testosterone by the gonads of the protandrous Rhabdosargus sarba at various sexual phases. AB - The in vitro steroidogenic capacity of the gonadal tissue in the protandrous Rhabdosargus sarba was studied. Testicular and ovarian tissues from various sexual phases were used either separately or combined. With progesterone as precursor, high yield of 5 beta-reduced metabolites, and no 11-ketotestosterone or 11 beta-hydroxytestosterone were found. The production of 5 beta-pregnan-3 alpha-ol-20-one and 5 beta-pregnane-3,20-dione was very high in incubations with testicular tissue from intersexes or males and was low in those with ovarian tissue only. The production of 17 alpha-hydroxyprogesterone was high in the female but was low in other sexual phases. With testosterone as precursor, 11 ketotestoterone and 11 beta-hydroxytestosterone were identified. The latter was the most abundant and prominent polar steroid in all incubations. 5 beta Reductase activity was high in the male and relatively low in the female. 5 alpha Reduced products, however, were absent. There was an increase in the production of androstenedione as the animal underwent sex reversal. The significance of this change in steroidogenesis in this protandrous fish is at present under investigation. Experimental results also indicated that in the intersexual gonad there may be interaction between the testicular component and the ovarian component in steroidgenesis. PMID- 4018558 TI - Seasonal variations in plasma testosterone concentrations in the male marsupial bandicoot Isoodon macrourus in captivity. AB - Although bandicoots in Queensland mate throughout the year, the majority of births occur in late winter and spring. To ascertain whether this seasonality in mating is manifest in the male reproductive system; body weight, testes size, and plasma testosterone concentration were examined in eight bandicoots throughout the year. The size of the testes increased with age in all bandicoots and there was no evidence of seasonal variation. Plasma testosterone concentrations fluctuated from 0.1 to 70.0 ng/ml and a seasonal cycle was observed, with a nadir in concentrations in March and a peak in September. The peak in testosterone concentration coincided with the period of the year when the majority of births occurred. Subsequent statistical analysis suggested that the annual plasma testosterone profile correlated well with the rate of change of day length. PMID- 4018559 TI - Seasonal changes in T3, FT4, and cortisol in free-ranging Svalbard reindeer (Rangifer tarandus platyrhynchus). AB - Serum levels of 3,5,3'-triiodothyronine (T3), free thyroxine (FT4), and cortisol were determined for free-ranging Svalbard reindeer during winter (March), summer (June-July), and autumn (October). A total of 48 animals representing adult males, adult barren, pregnant, and lactating females, and calves were shot, and blood sampled from their hearts. T3 and FT4 were found to vary seasonally, the levels being lower in winter than in summer or autumn. Differences due to state of pregnancy, sex, or age were represented by low FT4 levels in lactating females (summer) and rutting males (autumn), and high T3 levels in young calves (summer). Serum cortisol levels were found to change seasonally, summer levels being higher than winter or autumn levels in all groups of animals. This finding suggests that glucocorticoids (cortisol) do not affect the deiodination from T4 to T3 in reindeer. The seasonal changes in T3 and FT4 in wild animals were similar to the changes in captive animals. It is therefore concluded that the changes in thyroidal hormone levels do not indicate changes in basal metabolic rate in this species. PMID- 4018560 TI - Extrathyroidal conversion of thyroxine to triiodothyronine in Calotes versicolor. PMID- 4018561 TI - Epinephrine effect on carbohydrate metabolism in isolated and perfused catfish liver. AB - Two doses of epinephrine were infused for 6 hr into isolated catfish liver previously perfused with a glucose-free medium or with a medium containing 10 mM glucose. The hormone induced (a) a continuous decrease in liver glycogen level, both in absence and in presence of glucose in the medium; low dose of epinephrine was without effect on the decay of glycogen; (b) a great release of glucose, both in absence and in presence of glucose in the medium; the low dose of epinephrine induced an effect similar to the maximal dose, only in experiments without glucose in the medium; (c) no effect on lactate uptake by liver; or (d) a prevention of the decline in liver glycogen phosphorylase activity observed during 1 hr incubation of liver slices. It has been concluded that epinephrine caused an increase of glucose in perfusion medium with different mechanisms according to the level of glucose and the dose of epinephrine. High doses of hormone cause the glycogenolysis by activation of glycogen phosphorylase, both in presence and in absence of glucose; low doses of epinephrine probably preferentially promote in liver the gluconeogenetic processes in glucose-free experiments. PMID- 4018562 TI - Ovarian inhibition of juvenile hormone synthesis in the viviparous cockroach, Diploptera punctata. AB - The mature ovary can actively prevent increases in rates of juvenile hormone (JH) synthesis by corpora allata (CA). This was unequivocally shown in two ways. (1) By combining in a single host female one ovary known to be stimulatory and one known to be nonstimulatory. Since the combination of a stimulatory and nonstimulatory mature ovary resulted in rates of JH synthesis intermediate between those found following implantation of either of these ovaries alone, it is concluded that the nonstimulatory mature ovary is indeed inhibitory (a nonstimulatory immature ovary had no such inhibitory effect). (2) By implanting nearly mature ovarioles and female CA into males. The ovarioles prevented the increase in rates of JH synthesis by the implanted CA that occurs in the absence of implanted ovarioles. This ovarian-elicited difference in rates of JH synthesis by CA implanted into males was not accompanied by differences in hemolymph ecdysteroid titers. Also, following removal of nearly mature ovaries from normal females the rates of JH synthesis remained above those of control females for only 24 hr and then declined to rates of controls. This suggests that there is an additional factor regulating the decline in JH synthesis at the end of the gonadotrophic cycle. PMID- 4018563 TI - Stimulus requirements for prolactin and LH secretion in incubating ring doves. AB - To study the regulation of prolactin secretion and incubation behavior during breeding, stimuli available during the prehatching period were manipulated, and plasma prolactin and LH and pituitary prolactin concentrations were assayed. Four groups were compared: (a) nest and eggs removed (b) eggs replaced with infertile eggs, (c) eggs replaced with infertile eggs and partners separated, and (d) unmanipulated controls. The increase in prolactin secretion that normally occurs at the end of incubation was reversed when the nest and eggs were removed but was unaffected by the absence of the mate. Prolactin secretion was not maintained in males sitting beyond the normal incubation period (on infertile eggs), while it was maintained in females but only in the presence of the mate. In the control birds, the increase in plasma prolactin was accompanied by an increase in pituitary content; while in the manipulated groups, an inhibition of prolactin secretion was associated with a transient increase in pituitary content. Plasma LH levels were low in control birds during the time of high prolactin secretion, and in all groups where the disruption of normal breeding stimuli caused an early fall in prolactin, there was a concomitant increase in LH secretion. In animals which had been separated from their mates and provided with a nest bowl and eggs, continuous observations of incubation behavior were made and plasma was sampled every third day. Parallel changes in prolactin and sitting behavior occurred in some of the animals, while others continued to incubate after prolactin had declined. In no instance did an animal which maintained high prolactin show a decline in incubation. This suggests that prolactin can serve to maintain incubation, while incubation does not necessarily stimulate prolactin secretion at this phase of the breeding cycle. PMID- 4018564 TI - Development and validation of a salmon prolactin radioimmunoassay. AB - A highly specific radioimmunoassay (RIA) for the measurement of prolactin (PRL) in the plasma and pituitary of salmonid fishes was developed using a rabbit antiserum to chinook salmon (Oncorhynchus tschawytscha) PRL. The PRLs purified from chinook salmon and chum salmon (O. keta) pituitaries showed exactly the same competitive inhibition curves in the RIA, regardless of iodination of either hormone. The displacement curves for pituitary extracts and plasma from several salmonids, including chum, coho, and amago salmon, rainbow trout, and Japanese charr, were parallel to the salmon PRL standard, whereas those from the eel, goldfish, carp, and tilapia showed negligible cross-reactivity. Negligible cross reactivity was also seen with plasma from hypophysectomized rainbow trout or coho salmon. None of the mammalian PRL or growth hormone (GH) preparations, bullfrog PRL, or presumptive chum salmon "gonadotropin" and eel "PRL" cross-reacted in the PRL RIA. Presumptive chum salmon GH showed less than 0.05% cross-reactivity. The RIA sensitivity was less than 0.1 ng of the salmon PRL standard per milliliter. The immunoreactive plasma PRL levels in mature chum salmon were below 1 ng/ml in seawater. The plasma PRL in females increased to about 8 ng/ml 1 day after transfer to fresh water, and high levels (2-4 ng/ml) were maintained during 3-7 days after the transfer. In contrast, when males were transferred to fresh water, an increase in plasma PRL was seen only 1 day after the transfer. A significant decrease in plasma osmolality was observed in both males and females after transfer to fresh water. No change was observed either in plasma PRL or osmolality, when fish were transferred from seawater to seawater. PMID- 4018565 TI - Circannual plasma androgen levels in free-living male great tits (Parus major major L.). AB - Seasonal variations of plasma androgen levels in free-living adult and juvenile male Great Tits (Parus major major L.) were measured by radioimmunoassay over a period of 5 years. In 4 of the 5 years a peak of androgen concentrations was observed during the breeding season (in 1 year during the prebreeding season, followed by a nadir during winter. Besides these circannual fluctuations, considerable variations in plasma androgen levels between comparable behavioral periods of successive years were noticed (187 to 18.5 ng/dl during the breeding season and 86 to 16 ng/dl during winter). No relationship was found between these variations and possible causative factors such as age and origin of the birds and the time of trapping and blood sampling during the day. The large between year variations in androgen levels may be caused by changes in the birds' environment including density of the population and the availability of food. Additional data are required to test this hypothesis. PMID- 4018566 TI - Effect of mammalian growth hormone on amino nitrogen mobilization in the eel. AB - Hypophysectomy decreased plasma amino nitrogen (PAN) levels of Japanese eels. In contrast, administration of bovine or ovine growth hormone (GH; 2 micrograms/g) produced a delayed increase in PAN levels of both intact and hypophysectomized eels 48 hr after GH injection. The minimum dose of GH required to elevate PAN levels was found to be 0.1-1 micrograms/g body wt. The fact that GH treatment also increased PAN of hepatectomized eels indicates that the increased PAN was at least partly caused by the increased mobilization of amino nitrogen from body protein. GH also increased plasma free fatty acid content of intact and hypophysectomized eels 48 hr after GH injection in one experiment of the present study, but this effect was not reproducible in other experiments. No effect of GH administration was observed either in plasma glucose and lipid of intact and hypophysectomized eels 48 hr after the injection. PMID- 4018567 TI - In vivo and in vitro effects of growth hormone on the incorporation of [14C]leucine into protein of liver and muscle of the eel. AB - In vivo administration of ovine GH (2 micrograms/g body wt) increased [14C]leucine incorporation into protein of the liver, skeletal muscle, and opercular muscle of hypophysectomized eels. Addition of ovine GH into the medium (5 micrograms/ml) slightly increased [14C]leucine incorporation into protein of liver slices during 5 hr in vitro incubation, but did not affect protein synthesis from [14C]leucine in opercular muscle. In vivo pretreatment with ovine GH (2 micrograms/g body wt) 48 hr prior to tissue preparation clearly increased [14C]leucine incorporation into protein of liver slices in vitro. However, no statistically significant change was observed for in vitro incorporation of [14C]leucine into protein of opercular muscle of hypophysectomized eels which had been previously treated with ovine GH (2 micrograms/g body wt). These results indicate that ovine GH has a protein anabolic action in the liver and muscle of the eel and that compared to mammals a rather long lag period is needed to elicit such protein anabolic actions of GH in these animals. PMID- 4018568 TI - Gene interactions affecting muscle organization in Caenorhabditis elegans. AB - Revertants of unc-15(e73)I, a paralyzed mutant with an altered muscle paramyosin, include six dominant and two recessive intragenic unc-15 revertants, two new alleles of the previously identified suppressor gene, sup-3 V, and a new suppressor designated sup-19(m210)V. The recessive intragenic unc-15 revertants exhibit novel alterations in paramyosin paracrystal structure and distribution, and these alterations are modified by interaction with unc-82(e1220)IV, another mutation that affects paramyosin. A strain containing both unc-15 and a mutation in sup-3 V that restores movement was mutagenized, and paralyzed mutants resembling unc-15 were isolated. Twenty mutations that interfere with suppression were divided into three classes (nonmuscle, sus-1, and mutations within sup-3) based on phenotype, genetic map position and dominance. The nonmuscle mutations include dumpy and uncoordinated types that have no obvious direct effect on muscle organization. Two recessive mutations define a new gene, sus-1 III. These mutations modify the unc-15(e73) phenotype to produce a severely paralyzed, dystrophic double mutant that is not suppressed by sup-3. Five semidominant, intragenic sup-3 antisuppressor mutations, one of which occurred spontaneously, restore the wild-type sup-3 phenotype of nonsuppression. However, reversion of these mutants generated no new suppressor alleles of sup-3, suggesting that the sup-3 antisuppressor alleles are not wild type but may be null alleles. PMID- 4018569 TI - A direct assessment of the role of genetic drift in determining allele frequency variation in populations of Euphydryas editha. AB - Estimates of allele frequencies at six polymorphic loci were collected over eight generations in two populations of Euphydryas editha. We have estimated, in addition, the effective population size for each generation for both populations with results from mark-recapture and other field data. The variation in allele frequencies generated by random genetic drift was then studied using computer simulations and our direct estimates of effective population size. Substantial differences between observed values and computer-generated expected values assuming drift alone were found for three loci (Got, Hk, Pgi) in one population. These observations are consistent with natural selection in a variable environment. PMID- 4018570 TI - The affected sib method. I. Statistical features of the affected sib-pair method. AB - The distribution of the number of HLA haplotypes shared by sibs affected with the same HLA-linked disease can be used to obtain information on the genetics of the disease. Since the inception of the use of sib-pair methods for the analysis of the HLA-associated diseases, the question has been raised of how to include families with more than two affected sibs in the sib-pair analysis. This paper presents appropriate weighting schemes. A procedure for estimating the frequency of the disease allele in the general population, under the assumptions of single allele recessive, additive, dominant and intermediate models, with negligible recombination (theta = 0) between the disease-predisposing gene and the HLA region, and no selective disadvantage of the trait, is also given. Cluster sampling techniques are used in the analysis. PMID- 4018571 TI - Abstracts of papers presented at the 1985 meeting of the Genetics Society of America. Boston, Massachusetts, August 11-15, 1985. PMID- 4018572 TI - Toward the integration of psychosocial services in the general hospital. The human services department. AB - This article describes an innovative administrative organization for the delivery of psychologic care in the contemporary teaching hospital that, by combining services under medical leadership, takes an evolutionary beyond multidisciplinary team approaches. The long-range goal of this organization is to provide cost effective psychosocial services in the general hospital while maintaining the unique role contributions of the participating disciplines. To allow for informed decision making in this process, the initial step has been to establish a collaborative data base for patient and staff tracking, program planning, and evaluation. PMID- 4018573 TI - Identification of persons with Munchausen's syndrome: ethical problems. AB - Many of the most difficult management dilemmas created by patients with Munchausen's syndrome lie at the interface of law and medicine. Does a legal physician-patient relationship survive the imposturing of these patients? Are physicians relieved of their ethical and legal obligations in general, and their promise of confidentiality in particular, when they discover the elaborate counterfeit that these patients have constructed? Should physicians disclose confidential information to others--indeed do they have an obligation to do so- in an effort to break the endless cycle of hospital admissions that these patients invariably seek? This paper presents three possible approaches to these problems, and suggests useful criteria for managing Munchausen's patients, gleaned from the law of privacy, providing physicians with a firm basis upon which to strike an appropriate balance of all competing considerations. Specific guidelines and criteria can be formulated for disclosing the identities of Munchausen's patients without unduly encroaching upon their legal rights as patients. PMID- 4018574 TI - Commentary: psychiatry and primary care. AB - The role of the psychiatrist in educating primary care physicians has evolved from one of leadership to that of weakened collaboration. Concurrently, other mental health professionals compete with the psychiatric physician for actual clinical referrals. The primary care physician's fear of loss of control, stigmatization from psychiatric labels, and issues of time and money are reasons cited for limiting psychiatric intervention. Although the consultation-liaison service has proved to be a useful vehicle for integrating psychiatric services in hospital settings, how best to integrate psychiatric education and service in the ambulatory-based practice is still a challenge. Issues of clinical uncertainty and medical responsibility that the primary care provider regularly experiences may offer solutions for reestablishing the psychiatric physician as the leader in such educational and clinical initiatives. PMID- 4018575 TI - Psychiatry and primary care: can a working relationship develop? AB - This article explores the relationship between psychiatrists and primary care physicians. Expectations and results of attempts to train nonpsychiatric physicians in the care of the mentally ill are reviewed. The failure of this effort, along with the stigma against psychiatry has led to poor treatment of disturbed patients by primary care physicians. Using other mental health professionals as both educators and clinicians in primary care training programs over the past 20 years has resulted in a different referral pattern system for the mentally ill than for any other group of patients. Although the gap between psychiatry and the rest of medicine has widened, there are models of interaction and cooperation that are explored. The development of consultation-liaison programs has been a most important effort. The need for all of medicine to recognize the relationship between mind and body is stressed. PMID- 4018576 TI - Teaching psychiatry to primary care internists. AB - Many patients who seek the care of primary care physicians are suffering from a wide variety of psychiatric disorders. Primary care physicians should become skilled in interviewing techniques and basic psychiatric differential diagnosis, management, and treatment approaches for some types of psychiatric disorders and learn to regularly consult with and make referrals to psychiatrists when appropriate. Psychiatrists should play a very active role in the education of primary care specialists. This should include observation of the physician interviewing patients with different types of psychiatric disorders in addition to didactic teaching and supervision on topics such as psychopharmacology. With mutual collaboration between primary care interests and psychiatrists the patients of both groups of physicians should receive better care and continuing education of both may occur through an ongoing dialogue. PMID- 4018577 TI - The benefits of a psychiatric consultation--liaison service in a general hospital. AB - In this period of increased governmental regulation and decreased reimbursement for psychiatric services by third-party carriers, a fully staffed and financially stable psychiatric consultation-liaison service in the general hospital may still generate significant benefits for patients, hospital administrators, and psychiatrists: an increased rate of diagnosis of psychiatric and medical disorders, a reduction in the length of stay of medical or surgical patients, a decreased utilization of medical services and the development of innovative consultation-liaison activities. This article summarizes these benefits and outlines training obstacles that must be overcome to increase cooperation between psychiatry and medicine so that these benefits may be realized. PMID- 4018578 TI - Panics, prolapse, and PVCs. AB - There is a group of patients who presents with intense anxiety and physical complaints suggestive of cardiac or gastrointestinal disease. These patients are more commonly women and complain of palpitations, lightheadedness, chest pains, and dyspnea. A work-up may reveal positive findings such as extrasystoles and mitral valve prolapse that appear to confirm the organic etiology of the symptoms. Evidence is presented that the positive findings serve to confuse the picture and are an impediment, rather than an aid, to the physician in making the correct diagnosis. Effective treatment using tricyclic antidepressants or monoamine oxidase inhibitors is suggested. PMID- 4018579 TI - Reintroducing the internship: reactions of three departments of psychiatry. AB - The reintroduction of the internship requirement has caused a number of changes in psychiatric education in the past decade. Many psychiatric educators and departments of psychiatry have been faced with the challenges of organizing internships and establishing an internship curriculum. This has been especially challenging because the psychiatrists involved have seldom had full postgraduate training in the fields being organized and have not previously administrated clinical services in those areas. The authors discuss the goals of the internship for future psychiatrists and the pros and cons of university versus community general hospital based internships for future psychiatrists, and find several potential advantages to the latter. Also discussed are their consistent observations of internship programs for future psychiatrists over the past decade in three geographically separate regions and in state and private institutions. They and most other faculty members in their respective departments believe that the reinstitution of the internship has had largely beneficial effects on future psychiatrists. PMID- 4018580 TI - Informed consent--mandating the consultation. AB - This article illustrates how a mandatory consult procedure identified treatable psychiatric problems. Using a computerized data-based format, 372 (37.4%) patients (the "judgment" group) of 996 psychiatric consultations were identified as referred to assess the patient's capacity to execute a consent form for a medical or surgical procedure. One hundred twenty-nine (35%) of the 372 patients thus referred by hospital mandate were given psychiatric diagnoses (DSM-II) by the consultant and received recommendations for primary psychiatric treatment. The "judgment" group had significantly more organic brain syndrome and psychoses associated with CNS conditions (p less than 0.001), whereas the "nonjudgment" group was diagnosed as exhibiting significantly more neurosis, alcoholism, psychophysiologic disorders, transient situational reactions, and personality disorders (p less than 0.001). Without a required psychiatric consultation sanctioned by administrative hospital mandate, the majority of the "judgment" cases with major psychopathology would not have been identified. The use of the mandated psychiatric consultation in the general hospital is discussed. PMID- 4018581 TI - Multiple sclerosis: understanding the psychologic implications. AB - To effectively care for individuals with multiple sclerosis (MS) the practitioner must be able to understand the common psychologic sequellae. These include not only those engendered by the patient's reaction to the disease, but also those reflecting alterations in central nervous system function. Although research literature on MS has many pitfalls and the quality of the results is thus uneven, important psychologic aspects of MS that have been consistently reported are depression and anxiety, euphoria, often in association with some degree of dementia, denial of illness or of impairments, irritability and apathy, coexisting psychiatric disorders, and cognitive impairment, particularly involving sensorimotor function, primary memory, and conceptual ability. PMID- 4018582 TI - General hospital psychiatry and deinstitutionalization: a systems view. AB - The shift in responsibility for the care of chronic mental patients has generated a variety of problems for general hospital psychiatry. In response to these new demands, general hospital psychiatry has evolved a variety of effective strategies. Nevertheless, widespread concern over the appropriateness of serving chronic patients in an acute care setting persists. The level and direction of general hospital psychiatry's involvement with chronic mental patients will vary according to the specific characteristics of a community's patient population, its goals for those patients, and the resources at its disposal for realizing those goals. General hospital psychiatry must make a serious effort to minimize its being forced into a reactive position by deinstitutionalization policies generated by distant authorities. It must assume, instead, its rightful position as an autonomous, but fully cooperative, element within the psychiatric service system. Only then can its responsibility to the chronically mentally ill, to other patients, and to its own integrity be assured. PMID- 4018584 TI - Failure to keep psychiatric follow-up appointments. PMID- 4018583 TI - Medical and surgical inpatients who referred themselves for psychiatric consultation. AB - Medical and surgical inpatients who referred themselves for psychiatric consultation are characterized. The 25 "self-referred" compared to 787 "others" referred to the Consultation-Liaison Psychiatry Division were more likely to state depression (52%/25%) and anxiety (36%/11%) as reasons for referral. "Self referrals" were less likely to be referred by physicians for behavior management (8%/23%), general diagnosis (4%/22%) or suicide evaluation (4%/25%). The "self referral" represents a challenge to the current medical model referral mechanism in which the physician controls access to consultants. The data indicate that there should be a mechanism for the patient's contribution to the referral process and that increased sensitivity to psychologic difficulties in coping with medical illness would improve the use of psychiatric consultation in the medical setting. PMID- 4018585 TI - [Genetic aspects of the reaction of humoral immunity to collagen in humans and animals. Report I. Analysis of polymorphism of autoantibody levels to collagen type I in mice NZB X NZW (F1)]. AB - The study of polymorphism of humoral immunoreactions to the type I (AC) collagen in CBA/Lac, C57B1/6-J inbred mice and NZB X NZW (F1) hybrids showed the presence of genetically determined variability of the above mentioned trait. The analysis of intralinear dispersions of AC levels in NZB X NZW (F1) mice revealed sex dimorphism and age variability of the trait. A suggestion was made that sex hormones are important factors in ontogenic formation and modulation of autoimmunity to the type I collagen in NZB X NZW (F1) mice. PMID- 4018586 TI - Aging-associated increase in intestinal absorption of macromolecules. AB - The intestinal permeability of aging rats to various molecular weight species of polyethylene glycol 400 (PEG 400) was studied. Animals received a bolus of PEG 400 by oral gavage and urine was collected for 6 h to assess its rate of absorption. Quantitation by gas liquid chromatography revealed that total urinary excretion of PEG 400 increased with aging. 34-week-old rats excreted 34.3% of the administrated dose while 43.6% was excreted in the urine by rats 133 weeks of age. This effect was more pronounced with the higher molecular weight PEG since excretion of the lower molecular weight PEG 282 decreased by 10.5% while PEG 634 excretion increased by 11.4% with aging. The increased permeability of the intestinal tract to higher molecular weight species of PEG may indicate that the intestinal protective barrier to the absorption of potentially harmful environmental substances may be less efficient in aging animals. If similar findings are found in aging humans, they may indicate increased potential for absorption of large antigenic or carcinogenic compounds from the intestinal lumen. PMID- 4018587 TI - Body composition in elderly people. II. Comparison of measured and predicted body composition in healthy elderly subjects. AB - The predictive values of the equations of Moore et al. and Hume and Weyers and the measured values of body composition were compared in healthy, carefully selected aged and young subjects of both sexes. In the case of young subjects, these prediction equations seem to be adequate, even if this could not be affirmed with certainty by our results. The equations of Moore et al. were found not to be adequate for elderly males, while they were only suitable for the determination of intracellular components in elderly females. PMID- 4018589 TI - Lymphopenia induced by acute bacterial infections in the elderly: a sign of age related immune dysfunction of major prognostic significance. AB - These studies were undertaken to investigate the effect of acute bacterial infections on the absolute number of peripheral blood lymphocytes (PBL) in an elderly population and to evaluate the prognostic significance of a decreased number of PBL in critically ill aged patients. The results show that a significant lymphopenia develops in elderly patients during the course of an acute bacterial infection whereas the same type of acute illness has no effect on the PBL count of younger subjects. The lymphopenia is not related to a particular localization of the infection nor to the type of bacterial pathogen. The prognosis of the bacterial infection is closely linked to the severity of the lymphocyte depletion and its outcome can nearly be predicted by monitoring the variation of the number of circulating lymphocytes during the early course of the disease. PMID- 4018588 TI - Autofluorescence of human skin fibroblasts during growth inhibition and in vitro ageing. AB - The increase in autofluorescence (AF) of human skin fibroblasts during their in vitro ageing and growth inhibition was investigated by means of flow cytophotometry. The cellular AF of in vitro ageing cultures increased while the relative number of (3H)-thymidine incorporating cells decreased. Therefore, the rate of accumulation of cellular AF during in vitro ageing of the cultures is inversely related to the proliferation rate of the culture. The rates of increase of AF varied widely among the cell strains, being the highest in cells from patients with Werner's syndrome. Upon growth inhibition in a confluent culture the net rates of increase of cellular AF were found to vary widely among the cell strains. The respective net rates of increase of AF of the cells from patients with Werner's syndrome and the Spielmeyer-Vogt syndrome were within the range covered by the normal cell strains. The ultrastructure of the bright AF cells from patients with Werner's syndrome and the Spielmeyer-Vogt syndrome differed from the ultrastructure of AF cells from control persons with regard to the morphology of their residual bodies, those from the patients contained more multilamellar and multivesicular structures. In sorted non-AF cells vitamin E was found to completely inhibit the accumulation of AF without affecting the formation of 'residual bodies'. We infer that cellular AF is caused by lipid peroxidative reactions and that the accumulation of AF is due to a decrease in cellular proliferation rate. PMID- 4018590 TI - Is primary biliary cirrhosis a different disease in the elderly? AB - We examined the presenting features, clinical course and prognosis in relation to age in 121 patients with primary biliary cirrhosis (PBC) for a mean follow-up of 4.6 years. 35 patients (29%) were over age 65 years at presentation/detection. There was a higher proportion of patients asymptomatic of liver disease in the older (over 65 years old) than younger (under 65 years old) group. The clinical features of PBC were less marked in the older patients both in number of symptoms (p less than 0.05) and in progression of serum bilirubin, a marker of prognosis (p less than 0.001). There was no difference in liver-related mortality between old and young patients during the follow-up period. Overall mortality in patients with PBC presenting over age 65 was no different from age- and sex-matched controls. PMID- 4018591 TI - The throwaway culture: job detachment and rejection. PMID- 4018592 TI - Participants' evaluation of educational/support groups for families of patients with Alzheimer's disease and other dementias. PMID- 4018593 TI - Age, trust, and perceived safety from crime in rural areas. PMID- 4018594 TI - Are the elderly overhoused? Definitions of space utilization and policy implications. PMID- 4018595 TI - Assessment of activity priorities and design preferences of elderly residents in public housing: a case study. PMID- 4018596 TI - The changing service needs of older tenants in planned housing. PMID- 4018597 TI - Inter-institutional relocation and its effects on psychosocial status. PMID- 4018598 TI - Building housing for the low-income elderly: cost containment in the Section 202 program. PMID- 4018599 TI - Predicting the outcome of psychogeriatric day care. PMID- 4018600 TI - Nutrition site service users: does racial background make a difference? PMID- 4018601 TI - The redistribution of America's older population: major national migration patterns for three census decades, 1960-1980. PMID- 4018602 TI - Social networks and adaptation. PMID- 4018603 TI - Neighbors' support of older widows who live alone in their own homes. PMID- 4018604 TI - The impact of creative drama training on psychological states of older adults: an exploratory study. PMID- 4018605 TI - [Characteristics of the regional blood flow in the lungs during the development of pneumoconiosis]. PMID- 4018606 TI - [Biological action of the dust from lead-barite ore]. PMID- 4018607 TI - [Retrospective oncological epidemiological research (the example of the wood working industry)]. PMID- 4018608 TI - [Work experience of the industrial hygienists of epidemiological health stations in preventive health inspections in Gorlovka]. PMID- 4018609 TI - [Industrial hygiene in scandium oxide manufacture]. PMID- 4018610 TI - [Prevention of vibration disease in the mining industry]. PMID- 4018611 TI - [Method of studying the job load of first-aid physicians]. PMID- 4018612 TI - [Comparative evaluation of test sensitivity in detecting the early signs of poisoning by terpene derivatives]. PMID- 4018613 TI - [Data for establishing the maximum permissible concentration of Vitan-2M copolymer in the air of a work area]. PMID- 4018614 TI - [Establishment of a health standard for sulfalene content in the air of a work area]. PMID- 4018615 TI - [Experimental data on a hygienic standard for 1,4-dichlorobutene-2 in the air of a work area]. PMID- 4018616 TI - [Allergenic activity of new amine hardening agents]. PMID- 4018617 TI - [Toxicological characteristics and the establishment of a MPEL for dimethylacrylic acid and its ethyl ether in the air of a work area]. PMID- 4018618 TI - [Photometric methods of determining phosgene and chlorine in the presence of hydrogen chloride in the air]. PMID- 4018619 TI - [Determination of the fungicide Bayleton in the air by thin-layer chromatography]. PMID- 4018620 TI - [Chambers for determining the rate of penetration of chemicals through the skin]. PMID- 4018621 TI - [Characteristics of the dust factor and the course of anthracosilicosis in the underground transport workers of coal mines]. PMID- 4018622 TI - [Immunoglobulin levels in cervical mucus in patients with grade Io cancer of the cervix uteri and precancerous conditions]. PMID- 4018623 TI - [The course and management of labor in women with a history of cesarean section]. PMID- 4018624 TI - [Effect of cardiotocographic fetal monitoring on the type and frequency of obstetrical operations]. PMID- 4018625 TI - [Evaluation of the sensitivity to selected antibiotics of vaginal bacteria before cesarean section]. PMID- 4018626 TI - [Suggestions with regard to the management of twin pregnancies and labor]. PMID- 4018627 TI - [Complications and failures of using intrauterine contraceptive devices]. PMID- 4018628 TI - [Possibilities of the organ-sparing surgical treatment of leiomyosarcoma in young women]. PMID- 4018629 TI - Intestinal ischaemia. PMID- 4018630 TI - Intestinal function and intestinal blood supply: a 20 year surgical study. AB - The experience of The Middlesex Hospital in the investigation and management of chronic intestinal arterial occlusion (IAO) over a 20 year period is presented. Of some 100 patients referred only 28 were found to have IAO and these were critically evaluated in terms of insorptive and exsorptive function. No relation was found between intestinal performance and the degree of potential ischaemia suggested by angiography. Twenty two patients underwent reconstruction of the coeliac axis and mesenteric arteries, with three perioperative deaths. The remainder were followed for periods ranging between six months and 10 years. Of these, 15 are asymptomatic, one is unchanged, and one is subjectively worse. The role of elective surgery in relation to the visceral arteries is critically discussed in the light of these results, and in the perspective of the world experience. PMID- 4018631 TI - Altered solid and liquid gastric emptying in patients with duodenal ulcer disease. AB - Alteration in gastric emptying has been implicated in duodenal ulcer disease. The precise abnormalities remain controversial. We have used a radionuclide technique to assess solid and liquid gastric emptying in 14 patients with endoscopically proven duodenal ulcer and 22 healthy controls. Solid gastric emptying values for the patient group fell within the normal range. The median time taken for 50% (T50) of the liquid marker to empty from the stomach was 12 minutes (range 6-23 minutes) which was significantly faster (p less than .005) than controls (median 18 minutes, range 11-35). In 10 of the 14 patients, however, the rate of liquid emptying was within the normal range. There was no significant difference in the T50 for gastric emptying of solids between the groups, but in duodenal ulcer patients food left the stomach significantly earlier than in controls (p less than .05). After this, however, the linear rate at which duodenal ulcer patients emptied solid food from the stomach was a median 0.75%/minutes (range 0.5-1.4 minutes), which was slower (p less than .0005) than controls, median 1.25/minutes (range 0.7-2.3). These results show that the pattern of gastric emptying of digestible solids and liquids in patients with duodenal ulcer disease, as a group, is significantly altered. PMID- 4018632 TI - Relative nutritional value of whole protein, hydrolysed protein and free amino acids in man. AB - To compare their effects on nitrogen balance, diets containing either lactalbumin whole protein, its peptide-rich enzymic hydrolysate or an equivalent mixture of free amino acids as the sole source of dietary nitrogen were fed to two healthy subjects, each studied for 38 days on two separate occasions. The nitrogen intake (47 mg/kg body wt/day) induced a state of negative nitrogen balance, stimulating nitrogen conservation. Net daily nitrogen balance (mean +/- SD) in subject 1 was 0.23 +/- 0.72 g (amino acids) vs + 0.05 +/- 0.52 g (protein) and -0.21 +/- 0.58 g (amino acids) vs -0.05 +/- 0.57 g (hydrolysate), and in subject 2, -0.19 +/- 0.60 g (amino acids) vs -0.16 +/- 0.51 g (protein) and -0.42 +/- 0.35 g (amino acids) vs -0.62 +/- 0.34 g (hydrolysate). Analysis of these results by the cumulative sum technique showed no significant differences in the effect of the three nitrogen sources on nitrogen balance. This study indicates that there is no nutritional evidence to support the current practice of prescribing expensive enteral diets containing peptides or amino acids rather than the much cheaper whole protein to patients with normal gastrointestinal function. PMID- 4018633 TI - Effect of loperamide and naloxone on mouth-to-caecum transit time evaluated by lactulose hydrogen breath test. AB - The effect of loperamide and naloxone on mouth-to-caecum transit time was evaluated by the lactulose hydrogen breath test in four men and four women. Each subject underwent tests during the administration of placebo, loperamide (12-16 mg po), naloxone (40 micrograms/kg/h by a three-hour intravenous infusion), and loperamide plus naloxone, carried out at intervals of one or two weeks. The transit time was significantly longer after loperamide, and this effect was antagonised by the concomitant administration of naloxone whereas naloxone administered alone had no effect on mean transit time. No clinically important side effects were reported. PMID- 4018634 TI - Topical methotrexate alters solute and water transport in the rat jejunum in vivo and rabbit ileum in vitro. AB - The topical effect of methotrexate (MTX) on small intestinal hexose and ion transport has been studied using an in vivo steady state jejunal perfusion technique in the rat, and short circuited rabbit terminal ileum in Ussing chambers in vitro. In rat jejunum, perfusion with MTX (1 mumol/l) caused significant reductions in water, sodium, and glucose absorption within 110 minutes of exposure. Fructose absorption was, however, unimpaired. The same concentration of MTX, when added to the mucosal side of distal rabbit ileum caused significant increases in transmucosal potential difference, short circuit current and the unidirectional flux of chloride from serosa to mucosa. In the presence of a subphysiological magnesium concentration (0.3 mmol/l), MTX resulted in the abolition of net sodium absorption and the conversion of net chloride absorption to secretion. We conclude that MTX has a topical effect on small intestinal transport which is independent of its effect on crypt cell kinetics. PMID- 4018635 TI - Rectal mucosal morphologic abnormalities in normal subjects in southern India: a tropical colonopathy? AB - Electron dense bodies and vesicles were increased in undifferentiated crypt cells and differentiated colonocytes in the rectal mucosa of healthy volunteers in southern India. In addition, in the surface colonocytes lysosomes were increased, the cells were shorter with short irregularly grouped microvilli, there was evidence of cell immaturity and a high prevalence of spiral organism infestation. There was also alterations in goblet cell mucus granules, a reticulohistiocytic response in the subluminal lamina propria and residual evidence of vascular damage. These alterations indicate a non-specific response to mucosal injury. Such changes have not been observed in the rectal mucosa of temperate zone controls and could be designated tropical colonopathy. PMID- 4018636 TI - Distal transposition of rat caecum does not render it susceptible to carcinogenesis. AB - As the relative resistance of rat caecum to chemical carcinogens could reflect its luminal environment, caecal mucosa was exposed to the distal faecal stream in male Sprague-Dawley rats (n = 50) previously treated with azoxymethane (total dose 90 mg/kg sc). After colonic transection at the pelvic brim, the caecum was inserted isoperistaltically between colocaecal and caecorectal anastomoses (n = 30); an ileocolic anastomosis restored intestinal continuity. Controls (n = 20) had transection and reanastomosis at equivalent points of the bowel, plus caecotomy and resuture. Caecal crypt cell production rate, as determined stathmokinetically at 28 weeks, was not consistently affected by transposition. No tumors developed in either transposed or orthotopic caecum, apart from three suture-line tumours found at the caecotomy site in controls. The colonic tumour yield in controls (1.4 +/- 0.3 per rat : mean +/- SEM) matched that after transposition (1.5 +/- 0.2), but anastomotic tumours were twice as common after transposition (p less than 0.05) and rectal tumours were increased four-fold (p less than 0.05). The caecum remains resistant to carcinogenesis despite transposition to a distal colonic environment. Local epithelial defence mechanisms are more important than luminal contents in maintaining this resistance. PMID- 4018637 TI - Acute pancreatitis: a lethal disease of increasing incidence. AB - Between 1968 and 1979 650 patients in the Bristol clinical area suffered 737 attacks of acute pancreatitis. Sex distribution was approximately equal and mean age was 60 years. Comparison with the previous decade shows an increase in mean annual incidence of first attacks from 53.8 to 73.0 cases per million population. Case mortality was unchanged at 20%. In no less than 35% of fatal cases the diagnosis was first made at necropsy. Gall stones were detected in 50% of first attacks, predominantly in women. The proportion of alcoholics (8% overall) increased three-fold during the period of the study. In 23% of cases no aetiological cause was identified. Eighty patients suffered 99 recurrent attacks of acute pancreatitis, with a mortality rate (12%) that was not significantly lower than that of the first attack. Neglected gall stones accounted for 51% of these subsequent attacks. PMID- 4018638 TI - Medium term complications of endoscopic biliary sphincterotomy. AB - One hundred and fifteen patients were reviewed between 18 months and five years after successful endoscopic biliary sphincterotomy for choledocholithiasis, postcholecystectomy in 93 (81%). Thirteen (14%) postcholecystectomy patients and 11 (50%, p less than 0.001) with intact gall bladders are dead (cause of death was ascertained in each case). Of the others, 43 were interviewed and 48 completed a postal questionnaire. Stone free common ducts had been documented in 69 (76%), presumed in 16 (17%), and not achieved in six (7%, excluded from analysis). None of the responding patients had developed serious new problems. Current symptoms of those with and without gall bladders and those with 'documented' and 'presumed' duct clearance are similar. In no case has an episode of cholangitis since sphincterotomy been confirmed and only one patient has had documented recurrent duct stones. Continued incompetence of the sphincter was shown radiologically by the presence of bile duct gas in 14 (41%) of 32 patients. These results suggest that medium term complications of endoscopic sphincterotomy are unusual. PMID- 4018639 TI - Use of CAT scanning in the diagnosis and management of hepatic artery aneurysm. AB - Hepatic artery aneurysms occur infrequently and are often difficult to diagnose. Non-invasive procedures such as ultrasound or computer assisted tomography have not been considered suitable for definitive diagnosis and angiography is usually required. A patient is described in whom a mycotic hepatic artery aneurysm developed during the course of subacute bacterial endocarditis. The definitive diagnosis was made using computer assisted tomography with intravenous contrast enhancement and angiography was undertaken only as a prelude to transcatheter embolisation. The same technique was used to monitor progress after embolisation precluding the need for follow up angiography. As 80% of patients with hepatic artery aneurysm present for the first time after aneurysm rupture, the mortality associated with this condition is high. More widespread use of intravenous contrast enhanced tomography for abdominal examination in patients with unexplained abdominal pain might result in earlier diagnosis of this condition. PMID- 4018640 TI - Effect of cimetidine on gastric secretion and duodenogastric reflux. AB - In 19 subjects (four controls, one gastric ulcer and 14 duodenal ulcer) maximal gastric secretion was evoked with histamine 0.13 mumol/kg/h (0.04 mg/kg/h) for two to two and a half hours. A slow intravenous bolus dose of 200 mg cimetidine was given at the beginning of the last hour. Gastric secretion was measured before and after cimetidine administration and expressed both as mean acid output (mmol H+/h) and 'pyloric loss and duodenogastric reflux corrected' volume (Vg, ml/h). Mean reduction by acid output was 86%; mean reduction by corrected volume (Vg) was only 64%. The discrepancy, which is significant (p less than 0.01), is caused by a marked increase in duodenogastric reflux after cimetidine. PMID- 4018641 TI - Effect of cimetidine and omeprazole on aspirin- and taurocholate-induced gastric mucosal damage in the rat. AB - The effect of varying doses of cimetidine and omeprazole, on acute gastric mucosal lesions produced by topical aspirin (200 mg/kg; 1 ml/100 g) in 0.175 M HCl or topical sodium taurocholate (40 mM; 1 ml/100 g) in 0.175 M HCl was studied in the pylorus ligated rat. Preliminary studies revealed dose dependent inhibition of acid secretion with both cimetidine and omeprazole. Intraperitoneal cimetidine 50 mg/kg and 100 mg/kg given before topical acidified aspirin reduced mucosal lesions from a control score of 23.7 +/- 3.5 (mean +/- SEM) in which 83% of stomachs contained lesions, to 6.9 +/- 2.2 and 3.5 +/- 2.1 respectively (p less than 0.05), 36% and 27% of stomachs containing lesions. A dose of 250 mg/kg failed to reduce lesion score significantly (17.8 +/- 4.9) and 64% of stomachs contained lesions. Taurocholate-induced lesion score was reduced from a control value of 32.7 +/- 4.3 in which 97% of stomachs contained lesions to 10.8 +/- 3.3 and 15.5 +/- 3.8 by cimetidine 10 mg/kg and 25 mg/kg respectively (p less than 0.05), 62% and 68% of stomachs containing lesions. Cimetidine 50 mg/kg and 100 mg/kg failed to significantly reduce mucosal damage. Intraduodenal omeprazole (1.25 to 50 mumol/kg) given before topical acidified aspirin or taurocholate failed to reduce mucosal lesions, as did intragastric omeprazole 5 mumol/kg and 50 mumol/kg given before acidified aspirin. Cimetidine showed cytoprotective properties over a specific dose range beyond which the effect was lost despite continuing suppression of acid secretion. Omeprazole exhibited no cytoprotective activity. PMID- 4018642 TI - Gastric acid and pancreatic polypeptide responses to modified sham feeding: indication of an increased basal vagal tone in a subgroup of duodenal ulcer patients. AB - The effect of sham feeding upon gastric acid secretion and pancreatic polypeptide release was investigated in 28 patients with duodenal ulcer in order to evaluate whether high basal vagal activity is the cause of basal acid hypersecretion in patients with duodenal ulcer and basal secretion higher than 30% of their peak acid output. The patients were divided into two groups based on the ratio of basal/pentagastrin stimulated peak acid output (BAO/PAO) was higher or lower than 0.30: group A n = 19 (BAO/PAO less than or equal to 0.30) and group B n = 9 (BAO/PAO greater than 0.30). Gastric acid response to sham feeding (SAO) was significantly higher than basal level in group A (SAO: 11.4 mEq/h (2.5-20.1) vs BAO: 5.2 mEq/h (0.8-22.9), p less than 0.01, median (range)) while in group B the acid secretion did not increase with sham feeding (SAO: 9.6 mEq/h (4.5-13.6) vs BAO: 8.8 mEq/h (6.3-13.8) ns, median (range)). A negative correlation (r= 0.6118226, p less than 0.01) was found between acid increase expressed as basal subtracted sham feeding response (SAO-BAO) and BAO/PAO ratio of the entire group of duodenal ulcer patients (n = 28) suggesting that the greater is basal acid secretory capacity the smaller is acid increase in response to residual vagal activation. Pancreatic polypeptide response to sham feeding was higher in group A than in group B but no correlation (r = 0.20, n = 28) nor individual covariation was found between acid and pancreatic polypeptide secretions during vagal stimulation. sham feeding did not change serum gastrin. It is concluded that an increased vagal stimulation seems to be the cause of basal hypersecretion in a subgroup of patients with duodenal ulcer. The lact of correlation between the pancreatic polypeptide and acid responses to vagal stimulation interferes with the reliability of pancreatic polypeptide as indicator of vagal tone on gastric parietal cells. PMID- 4018643 TI - Origin of chronic right upper quadrant pain. AB - We have studied 22 consecutive patients referred for investigation of severe chronic right upper quadrant pain. The majority were women whose symptoms had been present for many years. All had undergone repeated investigations of the pancreatico-biliary, gastro-intestinal, urinary, and even gynaecological systems without a satisfactory diagnosis. Most had undergone at least one abdominal operation in an unsuccessful attempt to cure their pain. In 21 of 22 patients the customary pain was completely and reproducibly mimicked by balloon distension of the small or large intestine in at least one site. The trigger sites were jejunum (15), ileum (12), right colon (nine), and duodenum (six). In 12 more than one trigger site was found. Close questioning revealed features of the irritable bowel syndrome in the majority and depression in many though the symptoms were not spontaneously volunteered. Reproduction of pain has provided a convincing demonstration to this difficult group of patients that they have a sensitive gut and allows appropriate management. PMID- 4018644 TI - Environmental factors in aetiology of chronic gastric ulcer: a case control study of exposure variables before the first symptoms. AB - The aim of the present study was to determine whether there is indication that either smoking, alcohol ingestion, or ingestion of analgesic or non-salicylate non-steroidal anti-inflammatory drugs plays any role in the development of chronic gastric ulcer disease. A group of 104 patients with gastric ulcer was compared with an age, sex and social grade matched community control population as regards exposure to the above factors during three time periods--the lifetime, five year and one year periods before the initial onset of the patients' ulcer symptoms. In all three study periods a statistically significant risk of gastric ulcer was found to be associated with smoking, and the daily use of aspirin, indomethacin and of other non-salicylate non-steroidal anti-inflammatory drugs as a group, but not with alcohol or daily use of paracetamol. As exposure to the environmental factors preceded the initial onset of ulcer symptoms, causal relationships are suggested. Assuming the association are causal, it can be calculated that possibly up to 80% of gastric ulcer disease is attributable to smoking and the daily ingestion of analgesic and anti-inflammatory drugs. PMID- 4018645 TI - Does age influence normal gastro-oesophageal reflux? AB - Prolonged oesophageal pH monitoring is being used increasingly to detect abnormal gastro-oesophageal reflux. To assess the influence of age on normal reflux patterns, a group of 13 young asymptomatic subjects (mean age 22 years) was compared with a group of 14 middle aged asymptomatic subjects (mean age 49 years). An ambulatory system using a radiotelemetry capsule and a portable receiving system was used, oesophageal pH being recorded for at least 16 hours during an overnight hospital stay under standardised conditions. There was no significant difference in the duration or frequency of reflux episodes as defined by pH less than 5, less than 4, less than 3, or as a fall in pH of more than two units. It is concluded that it is an acceptable practice to use young volunteers to establish normal values in reflux studies of young and middle aged patients. PMID- 4018646 TI - Influence of morphine on the distal oesophagus and the lower oesophageal sphincter--a manometric study. AB - Basal pressure and relaxation of the lower oesophageal sphincter (LOS) as well as amplitude, duration and propagation velocity of peristaltic waves in the distal third of oesophagus were measured in 15 healthy adults (nine men and six women). A highly standardised technique was used employing manometric equipment including a low-compliance pneumohydraulic infusion system and a triple lumen recording catheter. After establishment of baseline manometry values the catheter was positioned with its distal orifice in the lower oesophageal sphincter. In 10 subjects 0.2 mg/kg body weight of morphine sulphate was then injected subcutaneously. In five others equal volume of saline was given. The manometric data were analysed blindly. Repeated manometric evaluations were carried out 15, 30, 45, 60, and 75 minutes after the injection. Morphine increased slightly LOS pressure and significantly (p less than 0.001) decreased LOS-relaxation, the maximal effect occurring 30 minutes after the injection. Amplitude of peristaltic waves increased slightly but insignificantly, whereas propagation velocity and duration were uninfluenced. The results of this study suggest that pharmacologic doses of morphine influence normal function of the LOS and possibly the distal oesophagus. The role of endogenous opiates in this respect, however, awaits further studies. It is suggested that abnormalities in opioid neurotransmission may explain some of the non-specific oesophageal motility disorders. PMID- 4018647 TI - Effect of warfarin on cell kinetics, epithelial morphology and tumour incidence in induced colorectal cancer in the rat. AB - The effect of low dose warfarin and high dose warfarin on epithelial cell kinetics (as determined by stathmokinetic techniques), and preneoplastic morphological changes was studied during azoxymethane induced carcinogenesis in the rat. Warfarin, at either low or high dose, had no effect on crypt cell production rate (CCPR) at any time interval whereas tumour incidence in both low dose warfarin and high dose warfarin groups was significantly reduced. Morphological changes were observed using scanning electron microscopy, which by conventional histology were shown to be adenoma precursors. In the control group the number of microadenomas increased with time after starting azoxymethane. In warfarin treated animals, the number of microadenomas also increased with time, but the actual incidence was reduced when compared with controls. These results suggest that the effects of warfarin on tumour development is unrelated to its anticoagulant effect, because increased dose did not result in greater tumour reduction. Furthermore, there was no overall change in CCPR when warfarin was administered. Warfarin may exert a specific effect, by preventing neoplastic change in cells which have undergone morphologically undetectable changes associated with early carcinogenesis. PMID- 4018648 TI - Morphometric study of the small intestinal mucosa in young, adult, and old rats submitted to protein deficiency and rehabilitation. AB - Linear and stereological morphometric methods were applied to the jejunal and ileal mucosa of young, adult, and old male Wistar rats submitted to protein deficiency and rehabilitation. The animals were fed ad libitum a 2% casein diet during 42 days and then received a 20% casein diet for 30 days. Food intake, body weights, and plasma protein concentrations were recorded. In the young protein deficient rats values of mucosal height, surface area, and volume of the lamina propria were significantly lower than those of their age controls in both jejunum and ileum. In adults the differences were less marked and in the old rats all parameters were found to be unaltered by the protein deficient diet. The surface to-volume ratio showed no significant differences between control and protein deficient in all three age groups, meaning that villus pattern did not change with protein deficiency. On rehabilitation, a striking difference between jejunum and ileum was observed in the young rats; all parameters returned to control levels in the jejunum, while they remained lower than those of their controls in the ileum. PMID- 4018649 TI - What is the significance of pancreatic ductal mucinous hyperplasia? AB - The prevalence, distribution, and clinical associations of pancreatic ductal mucinous hyperplasia were studied in 102 non-malignant pancreases. Ductal mucinous hyperplasia was found in over 60% of specimens and was frequently associated with increased fibrosis--occasionally resembling pancreatitis. Significantly more ductal mucinous hyperplasia was found in pancreas from patients who were receiving corticosteroid treatment. Neither a history of hypercalcaemia in the three months before death, diabetes mellitus, alcoholism, tobacco smoking, nor the presence of gall stones was associated with an increase in ductal mucinous hyperplasia. The age of maximum prevalence, and the distribution of ductal mucinous hyperplasia in the pancreas were similar to those of pancreatic carcinoma. These similarities may be because both ductal mucinous hyperplasia and pancreatic carcinoma are proliferative responses, rather than because ductal mucinous hyperplasia is a precursor of pancreatic carcinoma. PMID- 4018650 TI - Interpretation of the breath hydrogen profile obtained after ingesting a solid meal containing unabsorbable carbohydrate. AB - The extent to which monitoring breath hydrogen excretion provides information concerning the entry of the residues of a solid test meal into the colon was investigated in 89 normal subjects, and 11 patients with the irritable bowel syndrome. The profile of breath hydrogen concentration showed an early peak, that occurred soon after ingesting the test meal in 89% subjects. This was followed by a later more prolonged rise in breath hydrogen concentration. The early peak occurred well before a radioactive marker, incorporated in the test meal, reached the caecum and the data suggest it was predominantly caused by the emptying of the remnants of the previous meal from the ileum into the colon. This hypothesis was supported by direct measurements of the rate of delivery of ileostomy effluent in 12 subjects with terminal ileostomies. Fermentation of carbohydrate in the mouth may, however, contribute to the initial peak, but this contribution may be avoided by collecting gas samples from the nares. The secondary rise in breath hydrogen excretion was closely correlated with the arrival of the radioactive marker in the caecum (r = 0.91), p less than 0.001), though the time, at which the secondary peak of breath hydrogen excretion occurred was poorly correlated with the time that all the radioactive test meal had entered the colon. When lactulose was infused directly into the colon, as little as 0.5 g produced a discernible hydrogen response, which occurred within two minutes of the infusion. Increasing the rate of colonic infusion of a 50 ml solution of 10% lactulose from 0.02 to 0.15 g/min in five subjects significantly increased the breath hydrogen concentration. At infusion rates below 0.075 g lactulose/minute, the peak breath hydrogen response preceded the end ot the infusion, while at higher rates of infusion, the peak hydrogen response occurred after the end of the infusion. Although these results confirmed that monitoring breath hydrogen concentration usefully signalled the time taken for a meal containing unabsorbed carbohydrate to reach the colon, it did not reliably indicate the time when all of the meal had entered the colon. Finally, the use of the maximum increase in breath hydrogen concentration as an index of the degree of carbohydrate malabsorption assumes uniform rates of entry into the colon. PMID- 4018651 TI - Endoscopic variceal pressure measurements: response to isosorbide dinitrate. AB - An endoscopic pressure sensor has been evaluated in the measurement of oesophageal variceal pressure and its response to drug ingestion. The variceal pressure showed a highly significant correlation with the splenic pulp pressure (r = 0.97) in six patients with liver disease of diverse aetiology and with hepatic venous wedge pressure (r = 0.92) in eight alcoholic cirrhotic men. Intraduodenal infusion of isosorbide dinitrate in the cirrhotics produced no change in wedge pressure or endoscopic variceal pressure despite profound falls in arterial systolic pressure. Thus isosorbide dinitrate appears to be of no value in treating portal hypertension. This study establishes the endoscopic pressure sensor as a valuable tool in screening drugs in this condition. PMID- 4018652 TI - Development of impaired splenic function in intestinal lymphangiectasia. AB - We describe a patient with intestinal lymphangiectasia who developed hyposplenism and speculate that it resulted from chronic loss of lymphocytes into the gut. PMID- 4018654 TI - Endocervical stromal sarcoma--a case report. AB - A case of a stromal sarcoma in a cervical polyp is presented. The tumor was confined to the polyp as evidenced by the histological examination of the uterus and cervix after surgery. In spite of that the patient died of widespread abdominal metastasis 1 year after the initial diagnosis. PMID- 4018655 TI - Recurrent cervical cancer presenting as small bowel obstruction. AB - A case report of a patient with recurrent squamous cell carcinoma of the cervix is presented in whom the recurrence was confined to the gastrointestinal tract and omentum in the upper abdomen. No evidence of recurrent disease was present in the pelvis or paraaortic lymph node bearing areas. Possible mechanisms for this unusual location of recurrence are discussed. PMID- 4018653 TI - Propranolol disposition in cirrhosis. PMID- 4018656 TI - Five-year survival following combination radiotherapy and chemotherapy for recurrent mixed mesodermal sarcoma of the ovary. PMID- 4018657 TI - V factor (tumor volume) and T factor (FIGO classification) in the assessment of cervix cancer prognosis: the risk of lymph node spread. AB - An attempt was made by investigation of the operative specimens from 98 patients suffering from epidermoid carcinoma of the cervix to assess the relationship between lymphatic spread on one hand and tumor volume and anatomical stage on the other hand. Within the same anatomical stage the risk of lymphatic spread is more important as the tumor volume increases. The reverse is also true. Within the same volume the risk of lymphatic spread increases when cancer extends beyond the "cervix-parametrium" barrier. The anatomical classification based on the T factor deserves to be retained, classification which some wanted to replace by another one based exclusively on the V factor. PMID- 4018659 TI - Approach to the abdominal retroperitoneum in patients with gynecologic malignancies. AB - The treatment of patients with gynecologic malignancies is still widely dependent on clinical staging. The introduction of the concept of surgical staging has significantly altered treatment plans. Better staging allows better treatment and more accurate comparison of survival and cure rates. We describe a surgical technique to expose the abdominal retroperitoneum. Sixteen patients have been explored by this technique. There has been no apparent difficulty in this procedure, even when performed on obese patients. PMID- 4018658 TI - Laser or cryotherapy for cervical intraepithelial neoplasia: a randomized study to compare efficacy and side effects. AB - A randomized study was performed to compare efficacy and side effects of laser and cryotherapy: 51 patients were treated with laser vaporization and 50 patients with cryotherapy. Success rates for laser and cryotherapy were not significantly different. Success rates were significantly related to lesion size. Grade of CIN, positive endocervical curettage, parity, and age at treatment were not found to be related. Vaginal discharge, both in duration and amount, was significantly less in patients treated with laser vaporization, compared with cryotherapy, but pain and bleeding occurred more often in patients treated with laser vaporization. A brief review of possible sources of bias in comparative studies on laser and cryotherapy is given, indicating the preference for a randomized study. It is concluded that widespread introduction of laser facilities in smaller centers is not justified, because the success rates are not better than those of cryotherapy, and because the advantages of less discharge are outweighed by the high cost. PMID- 4018660 TI - Second primary malignancy in endometrial carcinoma patients. AB - An epidemiologic study of multiple primary malignant neoplasms in endometrial cancer patients in Israel is presented. During the 7-year period of the study, 104 patients (10.3%) out of 1007 patients diagnosed as having endometrial cancer had another primary cancer. There was a significant difference in the incidence of multiple primary cancers between various ethnic groups, women of European/American origin having higher incidence than women of Asian/African origin. A significantly higher than expected incidence of second primary cancers occurred at the following sites: breast (relative risk, 4.1), ovary (relative risk, 11.6), cervix (relative risk, 5.1), and colon (relative risk, 5.9). The prognosis was mainly influenced by the site of the second primary cancer. The increased incidence of multiple primary malignancies justifies a high level of alertness to the possibility of second primary cancer in endometrial cancer patients. PMID- 4018661 TI - Stage I endometrial carcinoma: a review of 140 patients primarily treated by surgery only. AB - One hundred patients with stage Ia and 40 patients with stage Ib endometrial carcinoma had hysterectomy and bilateral salpingo-oophorectomy performed as the only primary treatment. Sixty-two percent of the patients had well-differentiated tumors, 31% moderately differentiated, and 7% undifferentiated tumors. Information on myometrial invasion was not available. The overall 5-year survival was 0.92 and the 5-year survival by tumor grade 0.96, 0.90, and 0.80 for patients with grade 1, 2, and 3 tumors, respectively. Survival rates decreased significantly with increased tumor dedifferentiation. Prognosis was not affected by enlargement of the uterine cavity or by higher patient age. Of 7 cases of isolated vaginal or pelvic recurrence, 4 could by controlled by irradiation therapy. These results compared to reported results of combined therapy suggest, that in well-differentiated cases-the majority of stage I endometrial cancers combined therapy of surgery and irradiation presents no advantage over simple hysterectomy. PMID- 4018662 TI - Analysis of serum lactic dehydrogenase levels and its isoenzymes in ovarian dysgerminoma. AB - The usefulness of serum lactic dehydrogenase (LDH) levels and its isoenzyme analysis as potential malignant ovarian tumor markers was investigated in 74 patients, including 5 cases of ovarian dysgerminomas. In this study 41.7% of patients with ovarian adenocarcinomas of the common epithelial types and 29.4% of cases with metastatic ovarian carcinoma had elevated preoperative serum LDH levels. In contrast all 5 cases of ovarian dysgerminomas had extremely high levels of serum LDH prior to therapy, whereas all 11 cases of benign solid ovarian tumors had normal LDH levels. The analysis of LDH isoenzymes revealed that ovarian dysgerminomas had high levels of the two fast fractions of LDH, whereas other malignant ovarian tumors had elevated levels of the two slow fractions. The present findings indicate that serum LDH levels and electrophoresis of its isoenzymes may be of value in patients with ovarian dysgerminomas. PMID- 4018663 TI - The effect of postoperative external radiotherapy on cervical carcinoma stage IB and IIA. AB - Among 344 patients operated after intracavitary irradiation of cervical carcinoma stage IB and IIA, 55 had positive nodes in the operation specimen, 16 of these received no postoperative irradiation, 22 received pelvic irradiation without a boost dose to positive nodes, and 17 also received a boost. The crude 5-year survival was 52% for these 55 high-risk patients. All 3 patients with adenocarcinoma died. For squamous-cell carcinoma postoperative irradiation gave a later relapse and less distant metastases, but survival was not approved. Postoperative irradiation with a boost added, resulted in 3 recurrences among 16 patients, none in the treated volume, and only one complication. The numerically improved survival of this small group was not statistically significant, however. A randomized trial with and without postoperative irradiation with a boost dose, requiring 1100-1200 operated patients, would answer the question whether the observed improval is significant or not. PMID- 4018664 TI - Progesterone secreting Sertoli cell tumor of the ovary. AB - A 33-year-old woman presenting with secondary amenorrhea and galactorrhea was found to have a Sertoli cell tumor of the ovary. The neoplasm also had a sex cord tumor with annular tubules (SCTAT) component. Further investigations revealed that in many respects the patient was endocrinologically pregnant. She had markedly elevated serum estrogen and progesterone levels and the endometrium demonstrated pronounced decidualization, but there was no evidence of actual pregnancy. Estrogen and progesterone were demonstrated by immunohistochemistry to be present in both the Sertoli cell and SCTAT portions of the tumor. PMID- 4018665 TI - [Plastic surgery in prolapse and incontinence]. PMID- 4018666 TI - [Treatment of the prolapsed vaginal blind end]. PMID- 4018667 TI - [Surgery for the formation of a new vagina]. PMID- 4018668 TI - [Indication and technic of metroplasty]. PMID- 4018669 TI - [Carnitine for the stimulation of fetal lung maturation. Clinical case report]. PMID- 4018670 TI - [Micromanipulatory sperm injection. A new method in the treatment of infertile men?]. PMID- 4018672 TI - Natural killer cell activity after elective cesarean section under general and epidural anesthesia in healthy parturients and their newborns. AB - We studied the influence of elective cesarean section, under general and epidural anesthesia, on natural killer (NK) cell activity in 12 healthy parturients and in their newborns. The results of peripheral blood samples taken from the mothers before anesthesia and from the newborns 3 h after birth served as basal values against which the results of samples drawn on the 1st and 5th days following delivery were compared. A significant (p less than 0.05) decrease in the NK cell activity after surgery was found only in those mothers given general anesthesia. The differences between the studied groups were not, however, significant. NK activity in the peripheral blood samples of the newborns was not significantly different in the general anesthesia and in the epidural group during the follow up period. The results show that the depression induced by operative stress on the NK cell function of parturients can be, at least partly, prevented by using epidural anesthesia. PMID- 4018671 TI - Maternal and cord serum levels of tissue polypeptide antigen (TPA) in normal pregnancies. AB - The tumor antigen and cytoskeleton protein tissue polypeptide antigen (TPA) have been determined in maternal serum throughout pregnancy. TPA levels in serum from pregnant women (n = 70) were not different from those in nonpregnant women (n = 61) until pregnancy week 28, from which time levels increased until parturition. Duplex pregnancies (n = 7) had higher serum TPA concentrations than simplex pregnancies, which was significant in pregnancy weeks 28 (p less than 0.014) and 32 (p = 0.05). Maternal serum TPA concentrations did not change during abortion or parturition and the mixed umbilical blood concentration of TPA equaled that in the mother's serum just after parturition. The correlation between placenta weight and maternal serum TPA levels was significant (p = 0.025). The decline of TPA after labor indicated a t1/2 for serum TPA of 7.5 days. PMID- 4018673 TI - Effects of intra-amniotic isoxsuprine on amino acid placental transfer in rats. AB - Direct administration of isoxsuprine to the rat fetus increases placental transfer of 35S-methionine and this increase is statistically significant on day 17 as compared with intraperitoneal administration and controls (p less than 0.01; p less than 0.05). In contrast, no statistically significant differences were found between the groups on day 16. PMID- 4018674 TI - Functional cyst or ovarian cancer: histopathological findings during 1 year of surgery. AB - The histopathological findings recorded during 1 year in 101 women undergoing surgery for palpable ovarian tumors were analyzed with respect to patient age, medical history and presenting symptoms. Almost half of the women (43%) were younger than 30 years and functional cysts or normal ovaries were found in 66 out of totally 101 women. During the following 2 years 18 of these women were subjected to further gynecological surgery and 17 women were infertile. While surgical treatment of functional cysts in young women may be deleterious, 3 cases of ovarian cancer illustrate the diagnostic difficulties and the potential risk of neglecting surgery. PMID- 4018675 TI - Roentgenographic and mathematical analysis of first metatarsal osteotomies for metatarsus primus varus: a comparative study. AB - The operative effectiveness of five different first metatarsal osteotomies for nonarthritic hallux valgus and metatarsus primus varus were objectively evaluated roentgenographically. The series consisted of 120 feet (75 patients) seen over a 5-year period. The osteotomies were biplanar neck, Chevron, biplanar basilar, basilar concentric, and basilar concentric combined with a lateral closing wedge. All the osteotomies except for the Chevron had varying degrees of plantar displacement of the distal fragment and crossed Kirschner wire fixation. The operative techniques and failures are discussed. Special x-ray studies confirmed misleading pseudocorrections caused by bandage compression and intraoperative and early postoperative roentgenographic distortion. The Chevron gave the least correction, 2 degrees, and did not permit plantar displacement to obviate late metatarsal transfer lesions. The biplanar neck osteotomies were technically the simplest, giving 86% satisfactory corrections, averaging 4.3 degrees. The biplanar basilar osteotomies yielded the most erratic results. The poor results were due to medial tilt during fixation, thereby negating any correction. The technical difficulties with the basilar concentric osteotomy were overcome by the addition of a small lateral closing wedge. This procedure gave by far the most consistently good results with corrections of up to 12 degrees, averaging 7.9 degrees. PMID- 4018676 TI - A method of predicting the degree of functional correction of the metatarsus primus varus with a distal lateral displacement osteotomy in hallux valgus. AB - Metatarsus primus varus may be an important pathologic component in hallux valgus deformity. The correction of the pathologic intermetatarsal angle M1 M2 is essential for providing an acceptable alignment of the hallux. The distal lateral displacement osteotomy of the first metatarsal (Chevron or Mitchell) provides correction of the intermetatarsal angle M1 M2. The present paper describes a simple method of calculating preoperatively the maximum possible correction through such osteotomies. This method, based on the measurement of the length of the first metatarsal and the width at the osteotomy site, projects the amount of correction and, furthermore, provides the limits of angular correction through such osteotomies performed distally. PMID- 4018677 TI - Chevron osteotomy: analysis of factors in patients' dissatisfaction. AB - The results of all Chevron osteotomies for hallux valgus performed at the Mayo Clinic between January 1976 and June 1982 were reviewed at least 1 year after surgery. Of the total 157 patients with 228 operations eligible for inclusion in this study, 154 patients with 225 operations were interviewed. Complete satisfaction was expressed for 79.1% of the procedures, satisfaction with minor reservations for 12.9%, and dissatisfaction for 8%. For the osteotomies producing incomplete satisfaction, further investigation identified failure to achieve correction and technical errors as the most prominent factors. There were no cases of avascular necrosis, osteotomy nonunion, or hallux varus. PMID- 4018678 TI - Handwriting of the alcoholic. AB - Alcohol intoxication produces abnormal handwriting with manifestations that are thoroughly described in the literature of forensic science. A less known phenomenon is the peculiar handwriting changes found in alcoholics, especially individuals in the later stages of the disease. In addition to the two handwriting states of non-alcoholic drinkers (normal/sober and intoxicated) the alcoholic writer has a third state, handwriting done in withdrawal. Withdrawal is a state of tension resulting in handwriting characterized by irregularity, ataxia and tremor. This type of abnormal handwriting creates special problems of authentication requiring detailed background history and appropriate comparison specimens, but it can also be used to judge the writer's state of sobriety. PMID- 4018679 TI - Teenage suicide--the five-year Metro Dade County experience from 1979 until 1983. AB - A study of suicide among teenagers was performed on the case files of the Office of the Medical Examiner of Metro Dade County in Miami, Florida, U.S.A. during the years 1979 until 1983. A total of 65 cases were studied and analyzed as to age, race, sex, cause of death, blood alcohol content at autopsy, drugs detected at autopsy, location of incident, presence or absence of a suicide note, and the reason for the suicide. The majority of the cases involved 16-19-year-old white males who took their life by handgun wounds. Predominantly they were sober. They killed themselves at home and half the time a note was left. Frequent reasons for the suicide included 'lover's quarrels" or drug problems. PMID- 4018680 TI - Postmortem interval estimation from body temperature data only. AB - One of the most consistently used methods of postmortem interval estimation (PMIE) is by means of body temperature measurements. Several variations of this method exist, from simple 'rules of the thumb' to quite complex equations requiring a knowledge of body mass and height. All of these methods employ a certain degree of approximation and perhaps the use of standard values and tables, and all of them are susceptible to some degree of error. The present study, at the Department of Forensic Medicine, Leeds, was initiated by the Home Office to investigate the extent of the errors which might be encountered in the use of these methods, and to devise a more simple and accurate method. The method devised is called the time-dependent-z equation, for purely theoretical reasons. It will be referred to as the TDZE method. The TDZE method requires the measurement of two rectal temperatures, about 1 h apart, a little mental arithmetic and reference to a single standard curve. The method is valid for all bodies, obese or emaciated, clothed or naked, in all environmental conditions, without modification. Results of the use of the method on data collected from 67 coroner's cases compare favourably with the results obtained by the use of other methods on the same data. PMID- 4018681 TI - Serum strontium estimation as a diagnostic criterion of the type of drowning water. AB - The estimation of serum strontium in rabbits before and after death by drowning, in soft or hard water, or by barbiturate intoxication is highly promising as a method in medicolegal practice. It not only diagnoses drowning but also indicates the type of drowning water. Atomic absorption spectrophotometry is a good method for the estimation. PMID- 4018682 TI - The theoretical aspects of the time dependent Z equation as a means of postmortem interval estimation using body temperature data only. AB - It has been clearly demonstrated that the rectal cooling curve does not obey Newton's Law, which is exponential. The first success in modelling rectal cooling mathematically was achieved by Marshall and Hoare [1]. An amendment was made to the simple exponential curve which led to a good mathematical model, exhibiting the three main sections of rectal cooling, i.e. lag, linear and quasi exponential. The resultant method of postmortem interval estimation required a knowledge of the body mass and height. The present study has led to a totally different amendment to Newton's Law, which provides a means of postmortem interval estimation from body temperature data only. The derivation of the method, with a background on Newton's Law follows. PMID- 4018683 TI - Esterase D phenotyping of bloodstains and hair roots by low voltage isoelectric focusing. AB - A new isoelectric focusing method is described for phenotyping of esterase D in blood stains and hair roots. It permitted easy and rapid discrimination of six phenotypes determined by ESD*1, ESD*2 and ESD*7. Experiments showed it to be practicable in forensic stain work. In addition, this technique was also usable in phenotyping of ESD 5. PMID- 4018684 TI - [Reconstruction of the female breast with autologous tissue following mastectomy]. PMID- 4018685 TI - [Surgical treatment of liver metastases of colorectal cancers]. PMID- 4018686 TI - [Classification and prognosis of colorectal cancers. Evaluation with multiparameter flow cytometry]. PMID- 4018687 TI - [Benzopyrone in the therapy of postreconstructive edema. A clinical double-blind study]. PMID- 4018688 TI - [Psychosocial sequelae of unemployment. High demand for the differential diagnostic sense of the physician]. PMID- 4018689 TI - [Diagnosis and conservative treatment of intervertebral disk-induced diseases of the lumbar spine]. PMID- 4018690 TI - [Prognosis and diagnosis of thoracic aorta aneurysms. An analysis of 40 patients; 1: Symptomology, risk factors and prognosis]. PMID- 4018691 TI - [Polyneuropathy--an unpopular diagnosis?]. PMID- 4018692 TI - [Contraception in adolescents]. PMID- 4018693 TI - [Acupuncture must be learned in the same way as surgery. Development and possibilities for use of a traditional and yet current therapeutic method]. PMID- 4018694 TI - [Physical therapy in respiratory diseases]. PMID- 4018695 TI - [Surgery of the spleen--splenectomy versus spleen preservation]. PMID- 4018696 TI - [Embryo-fetotoxicity from the viewpoint of occupational medicine]. PMID- 4018697 TI - [Prognosis and diagnosis of thoracic aortic aneurysm. An analysis of 40 patients. 2: Value of diagnostic procedures]. PMID- 4018698 TI - [Antihypertensive action of verapamil. Results with a new delayed-action form for once-daily administration]. PMID- 4018699 TI - [Bleeding to death from the umbilical cord?]. PMID- 4018700 TI - [Effect of D-glucosamine sulfate on experimentally injured articular cartilage. Comparative morphometry of the ultrastructure of chondrocytes]. PMID- 4018701 TI - [Presentation of a new tachistoscopic test procedure for measuring functional hemisphere asymmetries of the optic field]. AB - A newly developed tachistoscopic test using visual half-field-stimulation was tried on a clinical population of 178 primary school children. Words and geometric figures were presented. The results showed inconsistent effects of increased tiredness on the one hand and training effects on the other hand, while doing the test. The amount of asymmetry in the performance was not effected. The construction of the test was based on results of a previous study with similar items on a normal population of the same age. Therefore the items within a pair of simultaneously presented words or geometric figures in the two visual half fields are generally of equal difficulty as perception is regarded. Therefore asymmetries in the perception are due to functional hemispheric asymmetry. Vertical oriented four-letterwords show no significant difference between reproduction from the right or left visual half-field. This discrepant finding regarding to the literature is discussed in respect of different methodology, different age distribution of the population, and different state of skills in reading and writing. Geometric figures showed marked asymmetries on the level of reproduction. Such items were much better recognized, if they were presented in the left visual half-field. PMID- 4018702 TI - [Schizoaffective psychoses in Germany and Japan--a transcultural psychiatric study]. AB - 71 Japanese patients, who were diagnosed as a schizoaffective psychosis (ICD 295.7) and admitted in the year of 1979 in the department of psychiatry of Nagoya City University Hospital and psychiatric ward of its branch hospital, were investigated on the following clinical features: Age of the first psychotic manifestation, heredity, premorbid personality, situation of manifestations, symptomatology, clinical course, somatic complications, EEG-findings and sorts of treatments. This group then was compared statistically with 71 German patients with schizoaffective psychoses, who were admitted in the year of 1980 in the psychiatric department of Munich University Hospital. The statistical differences between these two groups revealed mainly in their symptomatology, not in the other clinical features mentioned above exept a certain type of the premorbid personality and a certain situation of falling ill. As for the delusions, the delusion of reference was very commonly found among the Japanese group, but relatively few in the German (p less than 0,01). On the other hand, the delusion of guilt was much frequent among the German, but extremely rare in the Japanese (p less than 0,001). The depressive symptoms were more frequently seen in the German (p less than 0,001), whereas the catatonic symptomes were more commonly found in the Japanese. Delusion of possession was seen in the Japanese group exclusively. On the premorbid personality-types, the trait of the sensitive personality was more frequently found in the Japanese (p less than 0,05), however, when considering the situations of the manifestations, the inner familial conflicts were found much fewer in the Japanese (p less than 0,05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4018703 TI - [Scientific explanation as a language and its application to psychiatry]. AB - The concept of scientific explanation plays a crucial role in the methodological discussion within psychiatry. This article shows that since scientific explanation employs a language of its own, its syntactic, semantic, and pragmatic dimensions must therefore be analysed with the help of semiotics. The pragmatic dimension is given particular attention because, hitherto, it has been comparatively neglected in the methodological discussion within psychiatry. Furthermore, the concept of explanation is viewed as a problem sui generis and investigated, to begin with, independently of problems such as causality and teleology. By means of the problem of the ambiguity of inductive-statistical explanations, it is shown that scientific explanations which employ statistical laws without taking into consideration the pragmatic concept of the state of knowledge must necessarily come to incomplete and/or contradictory results. The state of knowledge (K) is defined as the set of propositions which are accepted as true by a person (x) at a given time (t). A more precise analysis shows that, within a given state of knowledge, an accepted proposition is generally seen as more or less probable where it can be assigned a value of credibility (B) which lies between 0 and 1. The force of an explanation, in the pragmatic-informative sense, thus consists in the fact that an explanation can increase the credibility value of an explanandum-event (E) through a presentation of particular circumstances (C) and of general laws (T) such that the following holds: BTUC(E) greater than B(E). Depending on the level of the absolute value of BTUC(E), a gradual differentiation is made with respect to the quality of pragmatic informative explanations. The various types of explanation can be differentiated according to the type of arguments employed in the explanans of a pragmatic informative explanation; the most important members of this family of explanations are the causal, functional, teleological, and dispositional elements. Finally, the concept of explanation is differentiated from that of understanding, another key concept in psychiatry. In this respect, it is important that the incorporation of pragmatic dimensions into scientific explanation must not be equated with the use of psychological categories; the latter are of importance solely for the concept of understanding. Furthermore, the notion is rejected that in psychiatry a higher value is to be attributed to explanation than to understanding. Rather, both concepts represent different approaches to psychiatric disorders, whereby each employs a language of its own. PMID- 4018704 TI - [Dilated cardiomyopathy: characterization by clinical and hemodynamic findings]. AB - Dilated cardiomyopathy, a disease of the heart muscle of unknown origin, is characterized by impaired systolic function and dilatation of the left and right ventricles. In the Federal Republic of Germany, there are an estimated 4000 to 5000 new cases reported yearly [40]. Pathologic-anatomic studies have demonstrated that, in addition to an extent of dilatation of all heart chambers dependent on the stage of the disease, up to 60% of those who die can be found to have intracardiac thrombi [37]. Specific histologic changes are absent [34]. Disturbances of the microcirculation, a defect of autonomic innervation and biochemical alterations have been postulated as possible causes [7, 33, 35]. Circulating and bound antibodies against myocardial antigens and pathologic cellular immunoreactions have been reported in association with both myocarditis and dilated cardiomyopathy; this, in turn, has led to the hypothetical assumption of a secondary immunopathogenesis after myocarditis [6, 9, 12, 18, 26, 33]. Clinical and hemodynamic findings encompass a wide spectrum. With a mildly impaired ejection fraction to values between 40 and 54%, in our patients there was an associated enlargment of the end-systolic and end-diastolic ventricular volumes to 60 and 115 ml/m2 (upper normal limits 35 and 95 ml/m2), respectively. Those with increasing degrees of left ventricular function impairment to ejection fractions less than 40%, had additionally pathologic elevation of the filling pressures. In patients with marked impairment of the ejection fraction to values of less than 25%, cardiac output was reduced and systemic and pulmonary vascular resistances elevated.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4018705 TI - Impaired plasma clearance of nicotinic acid and rifamycin-SV in Gilbert's syndrome: evidence of a functional heterogeneity. AB - Patients with Gilbert's syndrome (GS) have impaired clearance by the liver of some organic anions. We looked for possible differences in hepatic clearance of nicotinic acid (NA) and rifamycin-SV (R-SV) among GS patients, and examined the effect produced by these anions on the plasma levels of unconjugated bilirubin (UCB). Two subgroups of GS patients, GS1 and GS2, were differentiated according to their ability to handle R-SV and NA. Compared with a control group, the alteration of the half-life both of NA and R-SV was less marked in GS1 than in GS2. UCB plasma concentration after NA and R-SV loading was more greatly increased in GS2 than in GS1 patients. In addition, a striking correlation was found in all subjects studied between UCB and the half-life of NA and R-SV. These related alterations of plasma UCB and plasma half-life or organic anions suggests a common defect of hepatic uptake. It is hypothesized that this defect is located at the level of a hepatic plasma membrane carrier. PMID- 4018706 TI - Release of vasoactive intestinal peptide by intraduodenal infusion of HCl or fat and intramuscular injection of neostigmine in man. AB - A highly sensitive radioimmunoassay system for plasma vasoactive intestinal peptide (VIP) was developed to examine the effect of intraduodenal infusion of HCl or fat on the plasma VIP levels in healthy subjects, and the effect of intramuscular injection of neostigmine in patients with irritable bowel syndrome (IBS). Intraduodenal infusion of 100 ml of 0.1 N HCl or 10 g fat caused a significant rise in plasma VIP level. Neostigmine (12.5 micrograms/kg) produced a significant rise in plasma VIP level, and the plasma VIP response to neostigmine was significantly greater in the IBS group than in the normal group. These results suggest that VIP might play a role in the pathophysiology of IBS. PMID- 4018707 TI - Zinc deficiency as a problem in patients with Crohn's disease and fistula formation. AB - Zinc deficiency is common in patients with Crohn's disease (CD), especially in those with skin lesions and growth retardation. Patients with fistulas have been considered to be another group with zinc deficiency. We therefore determined serum zinc concentrations of 50 patients with CD. Zinc deficiency was diagnosed in 17 out of 50 patients (34%). Serum zinc concentrations of patients with fistulas were significantly lower than those of patients without fistulas, and zinc deficiency was found in 11/17 (65%) patients. Zinc deficiency may play a role in the formation and clinical course of fistulas. Therefore, in view of possible therapeutic implications, determination of serum zinc concentration in patients with CD and fistulas appears to be of value. PMID- 4018708 TI - The condition of the biliary tract and cholesecretion in cases of ulcerative colitis. AB - The functional condition of the biliary system and the changes in the biochemical composition of the bile were studied in 62 patients with ulcerative colitis. In most patients changes in the contractile and motor function of the gallbladder were observed. The rate of occurrence and the extent of these changes are associated with the severity and duration of the main disease. Disturbances in the biochemical composition of the bile were observed in all the groups of patients, but the most pronounced changes were found in severe cases of ulcerative colitis. The choleretic Flamin was introduced into the complex therapy of the patients with ulcerative colitis to make the correction of these disturbances possible. The examination program for the patients with ulcerative colitis is supposed to include the laboratory and roentgenologic investigations which characterize the condition of the biliary system. PMID- 4018709 TI - CEA and ferritin in chronic pancreatic disease: a comparative evaluation. AB - CEA and ferritin were determined in 90 subjects with the aim of comparing their value in the diagnosis of pancreatic malignancy. Ferritin was shown to be more sensitive than CEA in detecting pancreatic cancer patients (68.4% and 57.9%, respectively) all of whom were, however, in an inoperable stage. In contrast, CEA showed a higher specificity as compared to ferritin (77.4% and 47.2%, respectively), the latter being frequently increased in inflammatory conditions such as chronic pancreatitis. The simultaneous assessment of CEA and ferritin showed the highest sensitivity when either parameter was found to be pathological and the highest specificity when both were. The receiver-operating characteristic curves demonstrated that CEA is more discriminating than ferritin for all serum values. Neither ferritin nor CEA may be considered a practically suitable marker of pancreatic cancer. PMID- 4018710 TI - Small intestinal function in chronic relapsing pancreatitis. AB - In a prospective study, several parameters of small intestinal function have been assessed in 20 patients with chronic relapsing pancreatitis with and without steatorrhoea. By and large all routine parameters of small intestinal function were found to be normal. In particular, neither a previously reported high incidence of lactase deficiency, nor D-xylose malabsorption or vitamin B12 depletion was observed. However, there was a high incidence of abnormal 14C cholylglycine breath tests (40%), suggesting the presence of mild bacterial overgrowth. Occasionally, this condition was associated with diarrhoea and steatorrhoea, thus indicating that steatorrhoea remaining after high-dosage pancreatin supplementation might sometimes be due to bacterial overgrowth. PMID- 4018711 TI - A study on an artifact introduced by fetal bovine serum-supplemented medium. AB - The antiserum raised in (C3H/HeJ X A/J)F1 mice by repeated immunization with mitomycin c(MMC)-treated ASL-1 leukemia cells maintained in vivo reacted with all tumor and normal cell lines maintained in vitro, but not with cell lines maintained in vivo. The common antigens detected in tissue-culture cells (CATC) turned negative after short in vivo cultivation of in vitro ASL-1 cells, and turned positive after short in vitro cultivation of in vivo ASL-1 cells. Treatment of cultured cells with antibiotics (kanamycin, gentamycin) did not alter the reactivity to the a-CATC serum. However, the activity of a-CATC serum was reduced by mixing the anti serum with fetal bovine serum (FBS), and an antigen antibody precipitation reaction occurred between the serum and FBS. Antigens which reacted with this antiserum were indicated to be FBS-related. The antibody against FBS was incidentally produced by immunization with weakly immunogenic tumor cells treated with MMC in FBS-supplemented medium. This study reinforms that the presence of FBS bound to cell membranes can introduce artifacts in the serological analysis of antiserum. PMID- 4018712 TI - [Biomicroscopic observation of macular breaks]. AB - Ninety-five eyes from 90 patients with macular breaks were studied biomicroscopically using the E1 Bayadi-Kajiura preset lens. Retinal detachments due to macular breaks were present in 14 of the eyes. The prevalence of posterior vitreous detachments (PVD) was 44% in idiopathic senile macular breaks (66 eyes), 78% in highly myopic macular breaks (9 eyes), and 95% in secondary macular breaks (20 eyes). Opercula, indicated the presence of vitreous traction, were found in 48% of the senile cases, in 22% of high myopes, and in 20% of secondary cases. Most of opercula were seen in eyes with no PVD or partial PVD. In 4 eyes without high myopia, vitreous traction at the edges of macular breaks resulted in retinal detachment. PMID- 4018713 TI - [Basic study for cancer therapy with porphyrin derivatives and pheophorbide derivatives]. AB - The properties of Porphyrin and Pheophorbide derivatives with cyclic tetrapyrrole structure have a specific character to accumulate selectively in tumor tissues and destruct tumor cells by photodynamic action. Recently, Photoradiation therapy of cancer with Porphyrin derivatives has put into practice, but its indication is very limited. We examined fundamentally on tumor tissue affinity of various Porphyrin and Pheophorbide derivatives, aiming at expanding therapeutic indication and application. As materials we used 73 derivatives in total, including 14 Porphyrin derivatives, 32 Pheophorbide derivatives, 17 Porphyrin metal complex and 10 Pheophorbide metal complex, and examined about the relation between their side branches and their tumor tissue affinity by N2-pulsed Laser spectrofluorometry, using tumor-bearing Golden Hamster. Furthermore, we investigated substances connected with Hematoporphyrin derivatives (HPD) in tumor cells. As a result, we had the following conclusions. N2-pulsed Laser spectrofluorometry is useful for analysis of Porphyrin and Pheophorbide derivatives in vivo. In Porphyrin derivatives, those with dimer structure and acetyl radical have higher tumor tissue affinity than those without such structures. Existence of OH radical and dimer structure is dispensable for tumor tissue affinity of Pheophorbide derivatives. OH radical in Porphyrin metal complex and acetyl radical in Pheophorbide metal complex are important factors for tumor tissue affinity of them. It is suggested that Hematoporphyrin derivatives (HPD) in vivo combine with protein in tumor cells. PMID- 4018714 TI - [Studies on mechanisms of prolactin synthesis and secretion using perfusion system of rat pituitary cells]. AB - The direct effect of TRH, dopamine, and hypothalamic extract on prolactin (PRL) synthesis and release were studied in an in vitro perfusion system using female rat pituitary cells and rat pituitary tumor cells (GH3 cells). The cells were exposed to tritium-leucine containing medium during perfusion, and total amounts of released PRL were measured by radioimmunoassay (IR-PRL), while those of newly synthesized PRL by counting immunoprecipitated radioactivity of tritium-labeled PRL (IP-PRL). IP-PRL began to be released immediately after exposure to tritium leucine, and gradually increased to a plateau within five hours. After this period, calculated specific activity (SA; IP-PRL/IR-PRL) was unchanged by stimulation of TRH, but when TRH (10(-10)M-10(-8)M) was applied in the phase of increasing SA, decreased SA of released PRL was observed, indicating that TRH released previously stored PRL preferentially. Hypothalamic extract showed PRL releasing effect similar to TRH in point of decreasing SA. Continuous administration of TRH evoked pulsatile IR-PRL release, followed by a decrease to basal level, and had no effect on SA except pulsatile decrease coincident with pulses of IR-PRL. Dopamine inhibited PRL release without change of SA and was presumed to affect both newly synthesized and previously stored PRL. However, brief interruption of dopamine infusion evoked PRL release with a decrease of SA, indicating the release of previously stored PRL. In contrast with the heterogenous PRL responsiveness to TRH stimulation in normal pituitary cells, GH3 cells, a clonal strain of rat pituitary tumor cells, released PRL in response to TRH with a constantly increasing rate of SA. Thus the concept of functionally heterogenous subpopulations in normal pituitary mammotrope cells was supported. PMID- 4018715 TI - [Right ventricular dysplasia: clinical features compared with dilated cardiomyopathy]. AB - Five patients with right ventricular dysplasia (RVD) and 28 patients with predominantly left sided dilated cardiomyopathy (DCM) were studied. RVD was characterised by syncope, recurrent sustained ventricular tachycardia, which typically had a left bundle branch block pattern on the surface electrocardiogram, right heart failure, and faint or absence of the right ventricular free wall on the myocardial scintigraphy. Two-dimensional echocardiographic, radionuclide angiographic, and contrast ventriculographic studies were typical of the right ventricular abnormalities in both Uhl's anomaly and arrhythmogenic right ventricular dysplasia. Two of them were died suddenly. Pathologic examinations showed "parchment-like" thinning of portions of the right ventricular free wall and its replacement by adipose tissue, although such degenerations were not found in the septum and the left ventricle. By contrast, DCM was characterised by exertional dyspnea and short run ventricular tachycardia, most of which had a right bundle branch block pattern. Ten of them had left ventricular myocardial defects on the scintigraphy, of whom five died suddenly. Hemodynamic data showed that left ventricular dysfunction was predominant more than right ventricle. Thus we postulate that these two syndromes are manifestations of a congenital, pathophysiologic process - the "involved right or left ventricle" syndrome. PMID- 4018716 TI - [Familial goitrous cretinism with giant goiter and hyperthyroglobulinemia: report of two siblings]. AB - A 39 year-old-man and a 44 year-old-woman who was his elder sister were admitted to our hospital for study and treatment of goiter and hypothyroidism. Both had giant goiters. When he was about 3 years old goiter was first noticed since then the goiter slowly increased in size until the time of admission, while her goiter increased in size from when she was about 30 years old. Though both cases were already recognized as cretinism, they had not been treated. Perchlorate discharge test showed impaired iodide organification in both cases. Their serum thyroglobulin concentration was extremely high (1800 ng/ml). To our knowledge, there have been no case reports of goiterous cretinism due to impaired iodide organification with hyperthyroglobulinemia except the report by Hirota, Y. et al. PMID- 4018717 TI - Glucose and fructose feeding lead to alterations in structure and function of very low density lipoproteins. AB - Young male rats were fed regular lab chow, or a diet containing 66% of total calories as either glucose or fructose. Both experimental diets led to hypertriglyceridemia, with fasting TG concentrations after one week of 195 +/- 20 and 296 +/- 44 mg/dl for rats fed glucose and fructose, respectively, compared to 94 +/- 10 mg/dl in the control rats. Moderate changes in VLDL composition were observed with both test diets, characterized by slight increases in TG: protein ratio, and increased total cholesterol and phospholipid content. In addition, VLDL isolated from rats fed high carbohydrate diets were increased in size, with a mean VLDL particle diameter of 666 A and 720 A in glucose-fed and fructose-fed rats, as compared to 536 A in control rats. The changes in lipid composition and size of VLDL particles isolated from glucose and fructose-fed donor rats were associated with an increase in their rate of removal from the circulation following their injection into normal recipient rats (half-life time 2.4 +/- 0.2 and 3.2 +/- 0.3 min respectively) as compared to VLDL-TG derived from chow fed donors (4.1 +/- 0.2 min). These data indicate that diets high in either glucose or fructose can lead to both structural and functional changes in VLDL, and provide additional evidence that the ability of fructose to induce profound hypertriglyceridemia is not secondary to a defect in VLDL-TG catabolism. PMID- 4018718 TI - In vivo and in vitro effects of cholecystokinin octapeptide on the release of prolactin in rats. AB - The effect of cholecystokinin octapeptide (CCK-8) on the release of prolactin (PRL) in rats was studied in vivo and in vitro. Intravenous injection of 5 micrograms/100 g BW of CCK-8 resulted in significant increase in the plasma PRL level after 10 and 20 min. CCK-8 at concentrations of 10(-11) M to 10(-7) M also caused dose-dependent stimulation of PRL release from dispersed cells of rat anterior pituitary. On the other hand, dopamine inhibited PRL release from dispersed cells of rat anterior pituitary in a dose-related manner at concentrations of 10(-8) M to 10(-6) M. Release of PRL from the cells was increased by addition of K+ at high concentration (53 mM) in a Ca++-dependent manner. Addition of 10(-3) M verapamil to the incubation medium inhibited CCK-8 induced PRL release from the cells. Addition of dopamine (10(-7) M) to the incubation medium inhibited PRL release from the cells induced by CCK-8 or high K+ (53 mM). These results indicate that CCK-8 acts directly on the anterior pituitary cells to stimulate PRL release and that calcium ion is involved in the mechanism of this effect. PMID- 4018719 TI - Oxytocin in the cerebrospinal fluid and plasma of pregnant and nonpregnant subjects. AB - The oxytocin concentration in the cerebrospinal fluid (CSF) and plasma of pregnant women at term with and without labor pain were measured by radioimmunoassay and compared with those of non-pregnant women of matched age. The oxytocin concentrations in the CSF were 4.9 +/- 4.1 microU/ml (mean +/- S.D.) in pregnant women with labor pain, 4.1 +/- 2.4 microU/ml in those without labor pain and 4.0 +/- 2.8 microU/ml in nonpregnant women, and the oxytocin concentrations in the plasma of these subjects were 45.2 +/- 19.6, 17.1 +/- 22.2 and 7.0 +/- 5.3 microU/ml, respectively. Thus the oxytocin level in the CSF did not change appreciably even when the level in the plasma was raised in the pregnant women with labor pain. These findings suggest that oxytocin does not penetrate the blood-brain barrier, and that oxytocin in the CFS has little or no central role in parturition in women. PMID- 4018720 TI - The effect of calcium supplements on plasma alkaline phosphatase and urinary hydroxyproline in postmenopausal women. AB - Although calcium supplements are widely used in the treatment of osteoporosis, their beneficial effect is not conclusively established. We now report some effects of a calcium supplement (1 g/day) given for 6 to 12 weeks to 15 postmenopausal osteoporotic women. The mean fasting urinary hydroxyproline/creatinine ratio decreased from 0.021 +/- 0.002 to 0.015 +/- 0.001 (P less than 0.0025), indicating a significant reduction in bone resorption. The mean plasma alkaline phosphatase fell from 123 +/- 5 U/l to 104 +/- 3.1 U/l (P less than 0.01), probably representing some secondary reduction in bone formation following the inhibition of bone resorption. These results support the concept that calcium supplementation is useful in the treatment of postmenopausal osteoporosis. PMID- 4018721 TI - A comparison of stimulation of proline incorporation by human growth hormone and a two-chain modification. PMID- 4018722 TI - Gonadal steroids deficiency and prolactin response to a met-enkephalin analog in man. AB - The aim of this study was to ascertain whether there is a correlation between gonadal steroids and opioid control of prolactin (PRL) secretion. Four castrated men, aged 18 to 24 years were submitted to intravenous injection of 250 ug of a met-enkephalin analog (D-Ala2-Mephe4-Met-(o)-ol-Enkephalin, FK 33824) (DAMME). In normal men DAMME injection was also performed on the 6th day after treatment with clomiphene citrate (CC) (200 mg/day for 5 days), a specific nonsteroidal estrogen receptor blocker. In castrated men and in normal men after CC treatment, there was a lower PRL response to DAMME than in controls (P less than 0.0005). These results suggest that gonadal steroid deficiency seems to cause a change in the opioid system and/or dopaminergic control of prolactin secretion. PMID- 4018723 TI - 17-beta Estradiol and progesterone levels in plasma of rhesus monkeys bearing copper-T device. PMID- 4018724 TI - Neuropsychological deficit and regional cerebral blood flow in schizophrenic patients. AB - The paper examined the relationship between the scales of the Luria Nebraska Neuropsychological Battery and measures of cerebral blood flow in a sample of 51 chronic schizophrenic patients without a history of brain damage. Of 88 correlations between the two sets of data, 22 were significant at the .05 level. The measurement of left anterior gray flow were particularly predictive of LNNB scores, although all correlations were at a moderate level, ranging from -.24 to .38. The data are consistent with the hypothesis that neuropsychological testing performance in schizophrenics is related to brain function rather than merely reflecting deficits due to anxiety or other psychiatric features which have been hypothesized to invalidate neuropsychological assessment in this population. The data are also consistent with the notion that schizophrenia is more likely associated with left-anterior functioning, and that gray-matter measures in rCBF are effective predictors of neuropsychological performance. PMID- 4018725 TI - Family or individual therapy: the determinants of modality choice. AB - There are powerful non-rational forces in patients and therapists alike, and in the therapeutic context. These forces often determine whether individual or family therapy is chosen. Historical, cultural, and economic forces, patient and family motivations, and therapist preferences are all powerful determinants of modality choice. This is partly due to the newness of the field of family therapy, and will probably continue until we have a better conceptual grasp of family theory and nosology, the interrelation of individual and family pathology, and a clearer delineation of the criteria for these modalities. PMID- 4018726 TI - A wolf in sheep's clothing? Simultaneous use of structural family therapy and behavior modification in a case of encopresis and enuresis. PMID- 4018727 TI - Liver disease activity and hepatitis B virus replication in chronic delta antigen positive hepatitis B virus carriers. AB - Delta antigen is currently thought to reflect superinfection of the liver with a defective RNA virus (delta agent), requiring helper function from hepatitis B virus for its replication. To assess the influence of delta agent on hepatitis B virus replication in patients persistently infected with both viruses and showing chronic liver disease, we measured serum and liver hepatitis B virus DNA in HBsAg positive chronic liver disease patients who were either positive or negative for delta antigen in the liver. Hepatitis B virus DNA was assayed in the serum of 21 patients with delta antigen-positive/HBsAg-positive chronic liver disease and in 21 patients with delta antigen-negative/HBsAg-positive chronic liver disease matched for HBeAg/anti-HBe status and underlying liver histology. HBcAg and delta antigen in liver was determined by immunofluorescence or immunoperoxidase staining. In delta antigen-positive/HBsAg-positive chronic liver disease, serum hepatitis B virus DNA was detected transiently in 4 of 21 cases (19%) and was present in these patients at low levels (trace to 2+). In contrast, 9 of 21 (43%) delta antigen-negative/HBsAg-positive chronic liver disease patients were serum hepatitis B virus DNA positive, and five of these had high serum hepatitis B virus DNA levels (3+ to 4+). Serum HBsAg and anti-HBc titers were significantly lower in delta antigen-positive cases and correlated with reduced amount of HBcAg in the liver.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4018728 TI - Recombinant leukocyte interferon treatment of chronic hepatitis B. AB - We have investigated the efficacy of a relatively prolonged course of recombinant leukocyte interferon treatment in 14 chronic HBsAg-, HBeAg-, hepatitis B virus DNA- and DNA polymerase-positive carriers. alpha-Interferon was administered for 9 weeks. Six of 14 treated carriers have a sustained loss of HBeAg, hepatitis B virus DNA and DNA polymerase. Four subsequently lost HBsAg (28.5%). Elevated pretreatment SGPT concentrations, histologic chronic active hepatitis, an exacerbation of chronic hepatitis with an increase in SGPT concentrations in the last weeks of treatment and possibly recent onset of the carrier state was associated with complete inhibition of viral replication. None of 11 matched, untreated HBsAg-, HBeAg-, hepatitis B virus DNA- and DNA polymerase-positive carriers monitored during the same period lost HBsAg. The effect of recombinant leukocyte interferon may require an appropriate host-immune response. The efficacy of recombinant leukocyte interferon therapy is restricted, but it may be of benefit in a proportion of carriers, if these carriers can be precisely identified. PMID- 4018729 TI - Choline fails to prevent liver fibrosis in ethanol-fed baboons but causes toxicity. AB - To determine how choline supplementation affects the liver and whether it can protect against ethanol-induced liver injury, baboons were fed either normal or choline-supplemented diets, each with or without ethanol. Eighteen baboons were pair-fed for 3 to 4 years liquid diets with 50% of total energy as ethanol or isocaloric carbohydrate; ten animals were given our regular diets, whereas in eight the choline content was increased 5-fold. Six additional animals were fed individually with the control diets (with or without additional choline). With both ethanol-containing diets, ethanol intake was comparable and resulted in hepatic steatosis and striking mitochondrial lesions, with increases in serum bilirubin and SGOT, SGPT and glutamate dehydrogenase activities. In addition, of the five animals fed alcohol with the regular diet, one progressed to incomplete cirrhosis and two others developed perivenular and associated perisinusoidal fibrosis. Similarly, in the four baboons fed alcohol with choline supplementation, incomplete cirrhosis developed in one and perivenular fibrosis in two. Collagen deposition was demonstrated by immunoperoxidase with a specific antibody against procollagen Type III. These animals also displayed proliferation of myofibroblasts in the perivenular area and transformation of fat-storing cells to transitional cells in the perisinusoidal space, with associated enhanced collagen fiber deposition. Thus, in baboons, choline supplementation failed to prevent alcohol-induced steatosis and fibrosis. All parameters remained normal in the eight baboons fed the regular control diet. However, in the choline supplemented controls, serum bilirubin, SGOT and glutamate dehydrogenase activities increased moderately and serum albumin decreased. Occasional fat droplets appeared in hepatocytes with mitochondrial changes (enlargement and alterations of the cristae) and an abundance of "myelin" figures in the cytoplasm, indicating that choline supplementation exerts moderate hepatotoxicity. PMID- 4018730 TI - Hereditary chronic conjugated hyperbilirubinemia in mutant rats caused by defective hepatic anion transport. AB - A mutant rat strain is described with autosomal recessive conjugated hyperbilirubinemia. Transport of conjugated bilirubin and tetrabromosulfophthalein from liver to bile is severely impaired whereas uptake of organic anions from plasma to liver is normal. During the first 10 days of life, serum bilirubin levels are 147 +/- 11 mumoles per liter with 68.7% diconjugates and 27.9% monoconjugates. In adult rats, serum bilirubin is 33 +/- 8 mumoles per liter with 81.8% diconjugates and 12.1% monoconjugates vs. 0.3 +/- 0.1 mumole per liter unconjugated bilirubin in normal adult rats. Bile acid metabolism is only mildly affected. In young rats, serum bile acid levels are normal. In adult rats, bile acid levels are elevated to 49 +/- 11 mumoles per liter vs. 10 +/- 6 mumoles per liter in normal rats. The bile flow in mutant rats is reduced to about 50%. This might be caused by a reduction of the bile acid independent bile fraction. Liver marker enzyme activities in mutant rat serum are normal. Liver morphology is also normal. Total urinary coproporphyrin excretion is not elevated but urinary coproporphyrin isomer I excretion is increased, a pattern like that in Dubin-Johnson syndrome in humans. However, unlike Dubin Johnson syndrome, the mutant rats do not have the characteristic black hepatic pigment. These rats provide a unique model to study mechanisms of bile formation and cholestasis. PMID- 4018731 TI - Cimetidine inhibits the formation of the reactive, toxic metabolite of isoniazid in rats but not in man. AB - The hepatotoxicity of isoniazid in rats results from the metabolic activation of acetylhydrazine, a metabolite of isoniazid, by the cytochrome P450 monooxygenase system. Inhibition of the drug-metabolizing enzyme system with a compound suitable for clinical use such as cimetidine might therefore prevent liver injury in experimental animals and in patients on isoniazid without interfering with the antituberculous activity of the drug. To test this hypothesis, we studied the effect of cimetidine on acetylhydrazine-induced hepatocellular necrosis in rats and the formation of 14CO2 from [14C]acetylisoniazid, which provides an indirect assessment of the fraction of a dose of isoniazid metabolized via the toxifying pathway. Pretreatment of rats with 150 mg per kg of cimetidine significantly decreased the extent of hepatocellular necrosis produced by 100 mg per kg of acetylhydrazine and the formation of 14CO2 from [14C]acetylisoniazid. In man, however, 300 mg of cimetidine administered every 6 hr did not decrease the formation of 14CO2 from [14C] acetylisoniazid administered concomitantly with 300 mg of isoniazid; similarly, cimetidine did not affect the urinary excretion of isoniazid, acetylisoniazid, acetylhydrazine and diacetylhydrazine. These data demonstrate that the mechanistic information obtained in animal models cannot be applied readily in clinical practice and that measurable inhibition of acetylhydrazine metabolism to prevent isoniazid liver injury does not occur after administration of therapeutic doses of cimetidine to patients. PMID- 4018732 TI - Effects of anesthetic agents on bile pigment excretion in the rat. AB - Anesthesia-induced alterations in bilirubin conjugation were studied. Rats were fitted with bile duct and jugular vein catheters while anesthetized with diethyl ether, ketamine or pentobarbital. As anesthesia abated, bile was collected for the next 5 hr and analyzed for flow rate, total bilirubin excretion and bilirubin glucuronide composition. The high-performance liquid chromatography method used allowed direct analysis of bile without derivatization or extraction. Ether anesthesia was associated with a reversible suppression of diglucuronide formation and total bilirubin excretion, with reciprocal monoglucuronide changes. Bile flow and pigment excretion were variable with ketamine. Pentobarbital provided the most uniform excretion data, although the ratio of C-8:C-12 monoglucuronide varied with all drugs. These data are consistent with recently reported drug-induced alterations in hepatic uridine diphosphoglucuronic acid concentration and support the hypothesis that alterations in this substrate concentration are capable of influencing rates of hepatic glucuronide formation. PMID- 4018733 TI - Maternal transmission of duck hepatitis B virus in pedigree Pekin ducks. AB - A 14-month old female Pekin duck experimentally infected as an embryo with duck hepatitis B virus via the amniotic route has been a chronic carrier of duck hepatitis B virus with very high (P/N) values of DNA polymerase activity since hatching. All the progeny were, on evaluation for congenital infection, found to be duck hepatitis B virus positive by endogenous DNA polymerase reaction and electron microscopy. These offspring remained persistently viremic throughout the study. Maternal transmission therefore bred true to a total of 49 offspring--24 ducklings (less than 24 hr old) and 25 ducks--studied. Six of these 25 ducks matched for age and sex and bled weekly for 6 weeks exhibited fluctuating plasma levels of DNA polymerase activity. Higher DNA polymerase activity was detected in newly hatched ducklings than in older viremic ducks. This observation was corroborated with the results of electron microscopic examination of thin sections of liver. Duck hepatitis B virus particles, located within vesicles of rough endoplasmic reticulum in the cytoplasm of hepatocytes, were more abundant, and therefore more readily observed, in ducklings than in older ducks. PMID- 4018734 TI - Recovery of liver function in partially hepatectomized rats evaluated by aminopyrine demethylation capacity. AB - Aminopyrine demethylation was investigated in rats after a 70% hepatectomy to assess possible parallelism between the recovery of mass and function. Tests were performed by analyzing 14CO2 exhalation from 0.1 microCi per 100 gm of body weight of [dimethylamine-14C]aminopyrine given intraperitoneally with incremental doses of unlabeled drug. Early after 70% hepatectomy, Vmax was reduced by 52%. This discordance between mass and function was not due to extrahepatic aminopyrine demethylation, since liver exclusion reduced demethylation of aminopyrine to nearly nil. Whether it results from increased liver blood flow in the remnant liver is less clear: portacaval anastomosis provoked an identical fall in Vmax and liver blood flow, but aortal-portal fistula which increased liver blood flow by 70% did not modify Vmax. The early increase in Vmax could be related to a "hepatotrophic" factor of splanchnic origin which increased after partial hepatectomy and decreased after portacaval shunt. After the early period, Vmax, expressed per gram of actual liver weight, returned to control range. Throughout regeneration (4 to 144 hr), no modification was observed in Km nor in cytochrome P-450 concentration. Enzymatic induction with phenobarbital increased the demethylation capacity more than liver weight in intact and regenerating liver. Except for the first hours after partial hepatectomy or after enzymatic induction, the aminopyrine demethylation capacity directly correlated with liver mass and may be useful in evaluating liver regeneration in vivo. PMID- 4018735 TI - Opsonic activity of human ascitic fluid: a potentially important protective mechanism against spontaneous bacterial peritonitis. AB - The opsonic activity of 60 ascitic fluids from 47 patients was measured using a standard opsonophagocytic assay. Curve analysis of the opsonic activity compared to the ascitic fluid concentration of total protein, total hemolytic complement, C3 and C4 yielded correlation coefficients of 0.84 (p less than 0.001), 0.84 (p less than 0.001), 0.94 (p less than 0.001) and 0.92 (p less than 0.001), respectively. There appeared to be a threshold of concentration for each protein below which there was no killing of bacteria. Cirrhotic ascites had significantly (all p less than 0.001) lower concentrations of total protein and complement and less opsonic activity than noncirrhotic ascites (including malignant, cardiac and miscellaneous types). Perhaps it is the dilution of crucial antimicrobial proteins below a threshold which predisposes to spontaneous bacterial peritonitis. PMID- 4018736 TI - Increased serum levels of hyaluronate in liver disease. AB - Recent animal studies show that endothelial cells in liver sinusoids are the main site for removal of sodium hyaluronate from the circulation. Few data with respect to hyaluronate metabolism are available in man. Serum hyaluronate levels were measured in 119 patients with liver disease by a sensitive assay. The hyaluronate level was significantly increased in liver cirrhosis, in comparison with healthy controls and with patients with noncirrhotic liver disease. The results suggest a role for the human liver in elimination of hyaluronate from circulation. Quantification of serum hyaluronate may be a useful test of liver endothelial cell function. PMID- 4018737 TI - Localization of increased hepatic vascular resistance in liver cirrhosis. AB - To determine the localization of increased vascular resistance in cirrhotic liver, blood pressures were measured by a direct cannulation method at several key points in the hepatic vascular pathway in normal and cirrhotic rats. Cirrhosis was produced by feeding a choline-deficient diet. Blood pressures in normal rats were 110 mm H2O in the portal vein, 68 mm H2O in the terminal portal venule, 28 mm H2O in the terminal hepatic venule and 20 mm H2O in the inferior vena cava. In cirrhotic rats, blood pressures in the portal vein and the terminal portal venule were 173 and 100 mm H2O, respectively, while those in the terminal hepatic venule and the inferior vena cava were elevated only slightly above normal. These hemodynamic data suggest that an increase in vascular resistance in cirrhotic liver is present in the intrahepatic portal vein and sinusoids, but not in intrahepatic hepatic vein. In cirrhotic liver, stenosis and distortion were found in peripheral branches of the portal vein, and sinusoidal stenoses and a decrease in sinusoidal space were recognized. Accordingly, it is suggested that the increase in vascular resistance in the intrahepatic portal vein and sinusoids correlate with these structural changes. Although severe stenoses and distortion were found in hepatic vein branches, it was thought that they do not contribute to portal hypertension because of lack of increase in vascular resistance in the intrahepatic hepatic vein. PMID- 4018738 TI - Portal venous bile acids in cholesterol gallstone disease: effect of treatment with chenodeoxycholic and cholic acids. AB - We determined the serum concentrations of cholic, chenodeoxycholic and deoxycholic acids in portal and peripheral venous blood in 9 gallstone-free patients and 39 patients with cholesterol gallstones during standardized cholecystectomy. An accurate and specific gas chromatographic-mass spectrometric technique was used. The portal venous concentration of total bile acids was similar in gallstone-free and untreated gallstone patients (n = 20); there was no evidence of a reduced hepatic uptake of bile acids in the latter. Treatment with cholic acid (n = 10) was associated with a 70% increase in cholic acid and normal concentration of total bile acids. In chenodeoxycholic acid-treated patients (n = 9), the portal venous concentration of this bile acid was increased 3-fold; total bile acids were increased about 60%. The estimated hepatic uptake of cholic acid was slightly decreased during chenodeoxycholic acid treatment. The results indicate that neither bile acid inflow to the liver nor hepatic bile acid uptake is reduced in fasting patients with cholesterol gallstones, and treatment with chenodeoxycholic acid increases fasting inflow of bile acids to the liver. The latter may contribute to unsaturation of fasting hepatic bile during treatment with chenodeoxycholic acid. PMID- 4018739 TI - The intrahepatic biliary epithelium in the guinea pig: is hepatic artery blood flow essential in maintaining its function and structure? AB - To determine whether hepatic artery blood flow is essential in maintaining the function and structure of bile ductules/ducts, the acute effects of hepatic artery ligation on bile secretion and hepatic ultrastructure were examined in anesthetized, bile duct-cannulated guinea pigs. Sixty minutes after hepatic artery ligation, spontaneous bile flow (5.08 +/- 0.4 microliter per min per gm liver) was virtually the same as that before hepatic artery ligation (5.31 +/- 0.3 microliter per min per gm), as were the choleretic effects of 10 CU per kg per 30 min secretin (7.14 +/- 0.9 vs. 7.21 +/- 0.9 microliter per min per gm), 300 micrograms per kg per 30 min glucagon (6.72 +/- 0.9 vs. 6.59 +/- 0.8 microliter per min per gm) and 60 mumoles per kg per 30 min glycochenodeoxycholate (6.43 +/- 0.6 vs. 6.45 +/- 0.6 microliter per min per gm). The failure of hepatic artery ligation to affect bile secretory function could not be attributed to the existence of collateral arterial blood flow to the liver. First of all, hepatic artery ligation resulted in diminishing significantly hepatic venous, but not portal, oxygen content. More importantly, in isolated guinea pig livers, perfused through the portal vein alone, secretin, glucagon and glycochenodeoxycholate produced changes in bile flow and composition similar to those seen in vivo. Electron microscopy showed no major ultrastructural changes of hepatic parenchyma and biliary epithelium 2 hr after hepatic artery ligation, or 2 hr after perfusing the liver through the portal vein alone save for some portal edema in the latter instance.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4018740 TI - Acetaminophen-induced fulminant hepatic failure in dogs. AB - Results concerning morphological and biochemical changes following intravenous administration of different doses of acetaminophen in dogs are reported. Acetaminophen infusion, as a parenteral solution (500 mg per kg per 90 min), produced fulminant hepatitis characterized by a good correlation between Portmann's grade of lesion and percentage of necrosis. All animals died within 76 hr after intoxication. Analysis of biochemical parameters revealed positive correlation between serum bilirubin levels and severity of the hepatic lesion. The experimental model of acetaminophen-induced hepatotoxicity is proposed as a model for evaluation of the therapeutic efficacy of new medical and surgical procedures. PMID- 4018741 TI - The effect of ethanol on membranes. PMID- 4018742 TI - Relationships between liver histologic lesions and portal hypertension in patients with alcoholic cirrhosis. PMID- 4018743 TI - Phenotypic analysis of an established cell line derived from a patient with Hodgkin's disease (HD). AB - This report describes the phenotypic analysis of a cell line obtained from a female patient with the nodular sclerosing subtype of Hodgkin's disease (HD). The cell line has a neoplastic karyotype and is stable in culture in the absence of feeder layers or growth factors. Phenotypic analysis of this cell line shows that it cannot easily be characterized as either a lymphocyte, macrophage or granulocyte but resembles in its characteristics certain HD lines already described in the literature. The cell line carries the antigen defined by the Ki 1 monoclonal antibody, shows myeloid markers on a proportion of cells and has cytoplasmic UCH-T1. PMID- 4018744 TI - England's new commitment law. PMID- 4018745 TI - Separating psychological factors from brain trauma in treating a hyperactive child. PMID- 4018746 TI - Employee assistance programs: an overview and suggested roles for psychiatrists. AB - Although employee assistance programs are rapidly becoming the predominant vehicle for the delivery of mental health services in occupational settings, few programs employ a psychiatrist on either a part-time or a full-time basis. After providing an overview of the need for, cost-effectiveness of, and current status of employee assistance programs, the authors draw on their own experiences with employee assistance programs to present four broad categories of roles the psychiatrist can assume in such programs: clinician, supervisor and educator, administrator, and organizational consultant. Problems encountered in these roles are also discussed. PMID- 4018747 TI - Documenting the relationship between homelessness and psychiatric hospitalization. AB - Homelessness among mental patients is frequently associated with deinstitutionalization. In a study to clarify the relationship between homelessness and psychiatric hospitalization, data from Illinois statistical reports and from admission reports of a state hospital that serves about 75 percent of the undomiciled mentally ill population in Chicago were analyzed. The rate of homelessness had increased substantially among psychiatric admissions over the last decade and was even higher among applicants for hospitalization. The homeless had lower admission rates than the domiciled, largely because of differing paths of referral. Nearly 20 percent of the homeless left the hospital against advice, and relatively few were referred to licensed long-term-care facilities. Until various systems develop adequate responses to the problem, both the numbers and the visibility of the homeless mentally ill are likely to increase. PMID- 4018748 TI - Build a better state hospital: deinstitutionalization has failed. AB - The author cites increasing numbers of chronic, homeless, and neglected mentally ill people as evidence of the failure of deinstitutionalization and community care to live up to their promise to reduce chronicity, the need for long-term hospitalization, and even mental illness itself. He believes the state hospital system, despite having been maligned and nearly destroyed, has great therapeutic potential. It could provide extended care to acutely ill patients before they become chronically ill; restore the ability to pinpoint responsibility for patient care, which has been lost under community care; and provide a stimulating academic environment conducive to research into treatment of the mentally ill. PMID- 4018749 TI - Expand the community care system: deinstitutionalization can work. AB - The author argues that most of the mentally ill should be treated in the community, where they can develop the skills necessary to function in society. The state hospitals should be used only to treat the most unmanageable patients. The author blames the presently inadequate community care system on insufficient funding and on the tendency of states to divide newly available funds between community services and state hospitals so that neither system is adequate. But whereas community care's problems can be resolved through greater commitment of funds and other measures, the author contends, the shortcomings of the state system are built-in and intractable. He examines and refutes the arguments supporting a return to the state hospital system. PMID- 4018750 TI - Community coping skills enhanced by an adventure camp for adult chronic psychiatric patients. AB - The effect of a two-week wilderness camp on ten skill areas related to community survival of the chronic mentally ill was assessed both by participants, who were adult chronic psychiatric patients from two Oregon state mental hospitals, and by camp and hospital staff. Compared with 30 controls, the 48 participants improved on seven of the ten areas by the end of camp and maintained their improvements in four of the seven areas for several weeks following their return to the hospital. Although discharge and recidivism rates for participants and controls did not differ at six-month follow-up, participants spent a greater proportion of time in the community than did controls. The authors discuss the specific skills improved by the program and those that contributed to duration of community survival, as well as the program's cost-effectiveness. PMID- 4018751 TI - Aggravating stress and functional level as predictors of length of psychiatric hospitalization. PMID- 4018752 TI - Strategies in working with chronically unemployed mental patients. PMID- 4018753 TI - Communication with geriatric patients. PMID- 4018754 TI - Rise in LOS may signal case-mix changes. AB - Community hospital trends during the first quarter of 1985 showed little change from the patterns seen in 1984. As admissions continued to fall, hospitals continued to reduce personnel and beds, and expense growth remained moderate. One notable exception was the increase in lengths of stay as hospitals may be finding that increased case-mix intensity resulting from continued admissions reductions has limited further reductions in lengths of stay. PMID- 4018756 TI - Hospitals' employee benefits plans merit scrutiny for savings potential. PMID- 4018755 TI - Generic publications get marketing nod from hospitals. PMID- 4018757 TI - Quinlan case set pace for bioethics debate. PMID- 4018758 TI - Indigent care provider fights for fiscal health. PMID- 4018759 TI - What's the market for outpatient surgery? PMID- 4018760 TI - State regulation of MRIs appears to shift direction. PMID- 4018761 TI - Pittsburgh area is home of largest MRI joint venture. PMID- 4018762 TI - Survey predicts nursing budget cutbacks. PMID- 4018763 TI - Hospitals' 'hidden' education costs exceed budgeted expenses: study. PMID- 4018764 TI - Cost strategies of CEOs and materials managers diverge. PMID- 4018765 TI - Rehab program brings patients to life on 'Easy Street'. PMID- 4018766 TI - The next generation of health care services. Interview by Emily Friedman. PMID- 4018767 TI - Health promotion programs flourishing: survey. PMID- 4018768 TI - The CIO: an emerging hospital executive. PMID- 4018769 TI - Bank offers onsite preadmission testing. PMID- 4018770 TI - Managed care pricing strategies shifting. PMID- 4018771 TI - Insurance risk-sharing saves benefits dollars: expert. PMID- 4018772 TI - Fitness program can raise name recognition among senior citizens. PMID- 4018774 TI - The pathologist in the courtroom: peer review is needed. PMID- 4018773 TI - Case reports--desideratum or rubbish? PMID- 4018775 TI - Pathologic study of parathyroid glands in tertiary hyperparathyroidism. AB - Tertiary hyperparathyroidism is defined as persistent parathyroid hyperfunction developing from the secondary hyperplasia that occurs after restoration of renal function by dialysis or kidney transplantation. Controversy continues as to whether parathyroid adenoma or hyperplasia accounts for the autonomous hyperfunction. A review of 128 parathyroids from 41 patients with tertiary hyperparathyroidism revealed marked hyperplasia in 39 patients (95 per cent), with a predominance of chief cells, an abundance of oxyphil cells, and 10- to 40 fold increases in parathyroid mass. This hyperplasia was considered to be the predominant morphologic feature of tertiary hyperparathyroidism. Adenomas, found only in two patients (5 per cent), seem to be rare. Diffuse, moderately enlarged hyperplastic glands were found predominantly in patients with transplants, whereas nodular, markedly enlarged hyperplastic parathyroids were observed more frequently in patients treated by dialysis. In spite of the different patterns of hyperplasia and the different gland sizes in these two groups of patients, the grades of hypercalcemia were similar. The results of ultrastructural studies indicate that the majority of parenchymal cells in diffuse, and some cellular areas in nodular, hyperplasia may consist of cells with high secretory activity that do not respond normally to hypercalcemia. It is concluded that both increased parenchymal mass and cellular differentiation, leading to hyperactivity, account for tertiary hyperparathyroidism. PMID- 4018776 TI - Nonimmune hydrops fetalis: a challenge in perinatal pathology. AB - Autopsies were performed in 40 cases of nonimmune hydrops fetalis during the period from 1975 to 1983. In 25 cases specific anatomic diagnoses, including hematologic disorders, infections, chromosomal abnormalities, congenital anomalies, and tumors, were made. In the majority the diagnosis of hydrops fetalis was made prenatally by ultrasonography. The mean gestational age at delivery was 30 weeks; 23 infants were stillborn, and 17 died during the neonatal period. Body weights were consistently increased; peripheral edema and ascites were present in all cases and pleural effusions in all but two cases. Hepatosplenomegaly, cardiomegaly, and pulmonary hypoplasia were frequent findings. The most consistent microscopic changes involved endocrine organs. Islet cell hyperplasia and Leydig cell hyperplasia were common, and thyroid hyperplasia was found occasionally. The fetal zone of the adrenal cortex was often thick and composed of swollen, vacuolated cells. Enhanced extramedullary erythropoiesis was observed in all cases. Thirty-nine placentas were examined; 34 were edematous (mean weight, 547 g), with villous edema, excess erythroblastemia and normoblastemia, and occasional intravillous hematopoiesis. Nonimmune hydrops fetalis has a range of known causes. Thorough autopsy, including placental examination, is the most useful approach for determining the etiology. In 23 cases the probable or possible cause was established in this manner. Antibody studies should also be performed in all cases to exclude an immunologic etiology. Synthesis of clinical, serologic, and pathologic data offers prospects for rational management and prediction of recurrence. PMID- 4018777 TI - Pathologic features of Behcet's syndrome: a review of Japanese autopsy registry data. AB - The data recorded from 170 autopsies of patients with Behcet's syndrome in Japan during the period from 1961 to 1976 were analyzed. The patients had been in the second to the eighth decade of life, and the ratio of males to females was 5 to 2. A wide spectrum of pathologic findings was observed, with involvement of neurologic, ophthalmic, cardiovascular, pulmonary, gastrointestinal, visceral, genitourinary, and mucocutaneous systems. Some of the common acknowledged clinical features of the syndrome, such as oral ulcers, synovitis, retinal and cutaneous vasculitis, and venous occlusions, were underreported. This apparent discrepancy in an autopsy series may be due to the effects of treatment or the healing process, as well as to the possible incompleteness of the postmortem examination. The accessibility of recorded data in a national autopsy registry offers a unique opportunity for review of the pathologic features of Behcet's syndrome. PMID- 4018778 TI - Systemic Malassezia furfur infections in patients receiving intralipid therapy. AB - Systemic infection with Malassezia furfur was first reported in 1981 as a specific complication of Intralipid therapy in a neonate. Six additional patients, including three older than 16 years of age, were identified subsequently. All had received prolonged Intralipid infusion through central venous catheters. Pulmonary infection was documented in tissue in three cases, the clinical presentation was characterized by pulmonary infiltrates, fever, and, in the infants, thrombocytopenia. Two subgroups of patients appear to be at the greatest risk for Malassezia infection: neonates with cardiopulmonary disease and adults with severe gastrointestinal disease and immunosuppression. The documentation of pulmonary arterial lipid deposits in vessels that had been infiltrated by Malassezia organisms and the observation of organisms in small pulmonary thromboemboli suggest that these lipophilic and lipid-dependent organisms are introduced into the bloodstream from venous catheters and require high lipid concentrations to proliferate in tissue. PMID- 4018779 TI - Maternal floor infarction. AB - In an attempt to determine the frequency, course, and outcome of maternal floor infarcts, 39,215 placentas and pregnancies were reviewed. The disorder is somewhat misnamed, because it is characterized by heavy deposition of fibrin in the decidua beneath the placenta rather than by arterial occlusion and ischemic necrosis of villi. The fibrin in floor infarcts often extends into the intervillous space, where it envelops villi, causing them to become atrophic. The disorder was relatively frequent in the present study, being present in nearly one of every 200 placentas. Mortality was high, with 17 per cent of the fetuses being stillborn. It may be a recurrent disorder, because 50 per cent of the gravidas with floor infarcts, compared with 27 per cent of control subjects (P less than 0.001), had had prior abortions and stillbirths. Damage to the decidua basalis by ischemia or infection may initiate many floor infarcts. Atheroma in the decidual arteries, foci of decidual necrosis, and histologic evidence of low uteroplacental blood flow were more frequent in patients with floor infarcts. Low maternal blood volume may contribute to the low blood flow because maternal hemoglobin values were often abnormally high in gravidas in whom floor infarcts developed. Acute chorioamnionitis, which can damage the decidua, had twice the expected frequency in gravidas with floor infarcts. PMID- 4018780 TI - Mesenchymal and muscle-specific intermediate filaments (vimentin and desmin) in relation to differentiation in childhood rhabdomyosarcomas. AB - Twenty-one childhood rhabdomyosarcomas were divided into three groups on the basis of cytologic composition. The tumors in group P consisted entirely of primitive mesenchymal cells, whereas those in groups M and W were characterized by the additional presence of numerous round rhabdomyoblasts and strap cells, respectively. The tumors were studied for the universal mesenchymal intermediate filament vimentin, and for the muscle-specific intermediate filament desmin. Vimentin positivity, which tended to be more prominent in primitive tumor cells, was found in all tumors, whereas desmin was found especially in round rhabdomyoblasts and strap cells. Desmin-positive primitive cells were found only in groups M and W, not in group P. It was concluded that the differentiation from primitive mesenchymal cells to morphologically recognizable myogenic tumor cells is accompanied by an increase in desmin positivity and, presumably, a decrease in vimentin positivity. Moreover, the observations suggest the existence of a group of "committed" cells that are morphologically primitive, but desmin-positive. These cells might play an important role in the observed further differentiation of rhabdomyosarcomas under chemotherapy. PMID- 4018781 TI - Clear cell variant of medullary carcinoma of the thyroid. AB - A previously unreported clear cell variant of medullary thyroid carcinoma is described. This histologic appearance was observed in sections from both the primary thyroid tumor and a vertebral metastasis. This variant merits recognition because it may be confused with a variety of other tumors occurring in the thyroid that contain cells with optically clear cytoplasm. Immunohistochemical and ultrastructural studies can be helpful in establishing the diagnosis of these tumors. PMID- 4018782 TI - Plasma cell granuloma of the thyroid. AB - Plasma cell infiltrates in the thyroid are rare. They may represent several processes, such as localized plasmacytoma, multiple myeloma, or plasma cell granuloma (PCG). It may be difficult to distinguish these disorders on the basis of morphologic features in sections stained with hematoxylin-eosin. All may be composed of mature plasma cells, without admixed macrophages or lymphocytes, that infiltrate the thyroid and adjacent connective tissue. The identification of the uncommon, but benign, PCG is facilitated by immunohistochemical staining to demonstrate an admixture of plasma cells with cytoplasmic kappa and lambda light chains. The polyclonal nature of the plasma cell infiltrate distinguishes PCG from neoplastic plasma cell proliferation. PMID- 4018783 TI - Sarcoidosis presenting initially as breast mass: report of two cases. AB - The cases of two patients who presented with breast masses suggesting carcinoma and no other clinical features of sarcoidosis are reported. Biopsies in both patients revealed noncaseating, epithelioid granulomas. Mycobacteria, fungi, and foreign material were not identified. In one of the patients, other sites of involvement were discovered five years later. These cases illustrate that sarcoidosis should be considered in patients with granulomatous breast disease, even without evidence of disease elsewhere. PMID- 4018784 TI - Gastrointestinal Richter's syndrome. AB - The development of a diffuse large cell lymphoma of the stomach in a patient who had chronic lymphocytic leukemia is reported. Richter's syndrome localized to the gut has not been described previously. Morphologic and immunologic studies suggest that the diffuse large cell lymphoma arose from the same clonal proliferation, IgG lambda, as the initially detected serum monoclonal protein associated with the chronic lymphocytic leukemia. PMID- 4018786 TI - Microcalcifications in breast lesions. PMID- 4018785 TI - Trichosporon beigelii endocarditis as a complication of peritoneovenous shunt. AB - Trichosporon is a common cause of superficial mycotic infection but has rarely been associated with endocarditis. The case of a patient who had a peritoneovenous shunt for chronic intractable ascites due to Laennec liver cirrhosis is described. The shunt was revised on several occasions, and the last procedure was complicated by a draining skin sinus wound. To the authors' knowledge, this is the first reported case of Trichosporon endocarditis complicating a peritoneovenous shunt. PMID- 4018787 TI - Apocalypse movement. PMID- 4018788 TI - Autopsy reform. PMID- 4018789 TI - Two-dimensional gel studies of genetic variation in the plasma proteins of Amerindians and Japanese. AB - Genetic variation has been studied in plasma samples from 107 Amerindian children and their parents, and 110 Japanese children and their parents by means of two dimensional polyacrylamide gel electrophoresis. Twenty-three polypeptides were scored; the identity of nine of these is at present still unknown. Genetic variation was encountered in 11 of these polypeptides. We have previously reported that the index of heterozygosity was 6.2 +/- 0.7% for 20 "randomly selected", silver stained polypeptides scored for genetic variation in Caucasoids (Rosenblum et al. 1983b). For technical reasons only 11 of these 20 polypeptides could be routinely scored in preparations from the Amerindian samples. For these 11 polypeptides, the indices of heterozygosity in the three populations were: Amerindians, 4.5 +/- 0.6%; Japanese, 5.7 +/- 0.7%; Caucasoids, 8.0 +/- 1.1%. Even with these relatively small numbers some striking ethnic differences as regards individual polypeptides are apparent. PMID- 4018790 TI - DNA semi-conservative synthesis in normal and Fanconi anemia fibroblasts following treatment with 8-methoxypsoralen and near ultraviolet light or with X rays. AB - The effect of treatment with 8-methoxypsoralen (8-MOP) plus near-UV radiation (UVA) or with X-rays on the rate of DNA semi-conservative synthesis of fibroblasts from 10 Fanconi anemia (FA), two heterozygous, and three normal cell lines was studied. Following treatments with either X-rays or low doses of 8-MOP plus UVA leading to a majority of monoadducts over cross-links per genome, the FA and heterozygous cell lines were indistinguishable from normals: the transient inhibition of semi-conservative DNA synthesis was followed by the recovery of a normal rate of synthesis. In contrast treatment with higher (but not saturating) doses of 8-MOP plus UVA allowed us to distinguish two classes among the FA cell lines. One class demonstrated a pattern of recovery similar to that of heterozygous and normal cell lines. This indicates that in such cell lines, the predominant lesion in this condition, the cross-links, do not arrest DNA synthesis and are likely to be normally repaired. Another class of FA cell lines did not show a recovery of a normal rate of DNA synthesis even after prolonged post-treatment incubation and although the proportion of cells in S phase was similar to that of the strains of the first category. This indicates that in such cell lines the repair of cross-links is inhibited at some step which is not necessarily the incision one. PMID- 4018791 TI - Spontaneous 6-thioguanine-resistant lymphocytes in Fanconi anemia patients and their heterozygous parents. AB - The incidence of spontaneous 6-thioguanine-resistant (TGr) lymphocytes was studied in the peripheral blood collected from seven Fanconi anemia (FA) patients and five of their heterozygous parents using an autoradiographic or a lymphocyte cloning method. Five of the seven patients showed a significantly elevated incidence of TGr lymphocytes as compared to age- and sex-matched healthy controls. There was, however, no difference between FA heterozygotes and controls. These results suggest some variability among the patients similar to those reported in clinical and cytogenetic investigations. The basis for the increase in TGr cells in the patients is not known, but the inherent genomic instability reflected as increased frequencies of chromosomal aberrations is one possible explanation. PMID- 4018792 TI - A familial X-autosome translocation with the breakpoint in the "critical region". AB - We report a case of an X-autosome translocation t(X;4)(q13;p16) found in both sexes in three generations. The anomaly was diagnosed in a couple referred for cytogenetic investigation as a result of three spontaneous abortions. With the exception of the miscarriages there are no particularities in the gynecologic data of the woman or in the pedigree. In all 50 lymphocytes and in 66 of 68 fibroblasts investigated the normal X chromosome was the late replicating one. PMID- 4018793 TI - 9p Trisomy/18p distal monosomy and multiple cutaneous leiomyomata. Another specific chromosomal site (18pter) in dominantly inherited multiple tumors? AB - In this report a severely mentally retarded adult female with 9p trisomy/18pter monosomy is described. In addition to a 9p trisomy phenotype this patient presented with multiple cutaneous leiomyomata. The question is raised whether the concurrence of the chromosomal anomaly and the multiple skin tumors in this patient indicates another example of a specific chromosomal deletion (18pter) in a dominantly inherited multiple human tumor. PMID- 4018794 TI - Complex translocation in habitual abortion. PMID- 4018795 TI - Congenital aplasia of the vasa deferentia of autosomal recessive inheritance in two unrelated sib-pairs. PMID- 4018796 TI - A detailed analysis of chromosomal changes in heritable and non-heritable retinoblastoma. AB - Full cytogenetic analysis of 27 different retinoblastoma tumors is presented. Gross aneuploidy of chromosome arms 6p and 1q were very common, being observed in 15/27 and 21/27 tumors, respectively. However, we found that chromosome 13 was rarely missing: only 3/27 had a detectable monosomy affecting 13q14. Monosomy of chromosome 13 by small deletion or rearrangement was also not observed in any of 12 retinoblastoma tumor lines analyzed detail at the 300-400 chromosome band level. A novel observation in retinoblastoma was the discovery of non-random translocations at three specific breakpoints, 14q32 (4/12), 17p12 (5/12), and 10q25 (3/12). Genomic rearrangements similar to those described involving C-myc in Burkitt lymphoma 14q+ cells could not be demonstrated in the four 14q+ retinoblastoma lines using molecular techniques, and a probe mapping to the site implicated to have an activating role in lymphoma. These data suggest that there is a target for rearrangement at 14q32 but it is not the same sequence used in some Burkitt lymphomas. Two other breakpoints (2p24 and 8q24) coincided with the mapped position of cellular oncogenes, but also failed to show a molecular rearrangement with the oncogene probes. The breakpoints, 10q25 and 17p12, are constitutional fragile sites which may predispose these regions to act as acceptors of translocations in malignant cells. One line had double minute chromosomes, and was the only one of 16 (6%) tested with the N-myc probe which had an amplification. Different tumors from single patients with multifocal heritable retinoblastoma showed independent karyotype evolution. Unilateral non heritable tumors exhibited a high level of karyotype stability throughout both in vivo and in vitro growth. The various common patterns of aneuploidy and translocations probably confer an early selective advantage to malignant cells, rather than induce malignant transformation. PMID- 4018798 TI - alpha alpha alpha anti-4.2 Haplotype and heterozygous beta null thalassemia in a Sicilian family. AB - The presence of the alpha alpha alpha anti-4.2 haplotype and heterozygous beta null thalassemia in a Sicilian family is described. These findings confirm the presence in Italy of a leftward deletion (-alpha 4.2) and indicate that this may not be rare. Furthermore, although the beta thalassemia determinant in this family has a severe expression, the interaction with the triplicated alpha gene does not necessarily express itself as thalassemia intermedia. PMID- 4018797 TI - The organization of two related subfamilies of a human tandemly repeated DNA is chromosome specific. AB - Several clones containing clusters of repetitive elements were isolated from a human chromosome 22 specific library. An EcoRI-XhoI fragment of 860bp was subcloned and was shown to belong to a family of tandemly repeated DNA linked to the Y-specific 3.4 kb HaeIII band. This probe hybridizes to several sets of sequences or subfamilies. The most abundant subfamily is a 1.8kb long sequence containing one EcoRV site, and in most repeats, one AvaII and one KpnI site. Using human-rodent somatic cell hybrid DNA, we have shown that this cluster is present on human chromosome 9 although presence on chromosome 15 is not excluded. Another subfamily, 6.1kb long, appears to be exclusive of chromosome 16. By in situ hybridization with metaphasic chromosomes, these sets of repeats were mapped to the constitutive heterochromatin of a few chromosomes. Coexistence in one genome of long tandem repeats of distinct organization but similar length may represent the outcome of a continuous process of fixation of variant sequences. Homologous repeats are also abundant in four higher primate genomes (Orangutan, gorilla, chimpanzee, and man) but absent in other primates (African green monkey, rhesus monkey, baboon, and mouse lemur). PMID- 4018799 TI - Cytogenetic studies using various clastogens in two patients with Werner syndrome and control individuals. AB - Chromosome studies were performed on peripheral lymphocytes from two patients with Werner syndrome and two healthy control individuals to detect spontaneous and/or mutagen-induced chromosomal instability of this disease. Diepoxybutane, isonicotinic acid hydrazide, 4-nitroquinoline-1-oxide, and bleomycin were used as standard clastogens. While the spontaneous frequency of chromosomal breakage was much higher in lymphocytes from both patients than in the control cells, the basic rate of sister chromatid exchange (SCE) was found to be in the control range. The sensitivity to clastogens of the patients' cells, however, was not substantially increased as compared with the controls if the degree of multiplication of the spontaneous breakage rate or SCE frequency was taken as the basis for comparison. No indication of a greater inhibition of proliferation by the clastogens in the patients' cells than in normal cells was observed using BrdU-labelled lymphocytes. Thus, the lymphocytes from both patients of the present study lacked essential features of the classical chromosome instability syndromes. PMID- 4018800 TI - Genetic analysis of human lymphocyte proteins by two-dimensional gel electrophoresis. VII. Genetic polymorphism of cytosol polypeptide with molecular weight of 38,000. AB - We describe a genetic polymorphism of cytosol polypeptide with mol. wt. of 38,000 detected in phytohemagglutinin (PHA)-stimulated peripheral blood lymphocytes by two-dimensional gel electrophoresis. Three different electrophoretic phenotypes (type 1-1, 2-1, 2-2) of the polypeptide have been identified in a Japanese population. Family and population studies indicate that three phenotypes are determined by two common alleles at a single autosomal locus. Since the polypeptide is mainly present in cytosol of cells, we propose that the polypeptide be temporarily designated as cytosol polypeptide with mol.wt. of 38,000 (CP38) and that the gene for CP38 be designated as CP38. The gene frequencies of two common alleles (CP38(1) and CP38(2)) are 0.899 and 0.101, respectively, in a Japanese population. The data on gel filtration of cytosol proteins on a Sephadex G-100 column suggest that CP38 exists as a dimer in the cytosol. CP38 was observed in the wide range of different cells, including B lymphoblastoid cells, adult skin fibroblasts, HeLa cells, and erythrocytes. In 11 out of 72 individuals, the phenotypes of CP38 were different from those of adenosine deaminase which is similar to CP38 in subunit size, cell distribution, and allele frequencies. These data indicate that CP38 is a new polymorphic polypeptide encoded by an autosomal locus. PMID- 4018801 TI - Chromosome study of five cancers of the prostate. AB - Nonrandom chromosome changes were sought in direct preparations of tumour material from the primary site of four carcinomas and one leiomyosarcoma of the prostate. Two of the carcinomas had previously received oestrogen therapy. A deleted chromosome 10, del(10)(q24), was found in all four carcinomas and may represent a specific marker in prostatic carcinoma. Three of the carcinomas also had a deleted chromosome 7, del(7)(q22), while the fourth had a 7p+. Deleted chromosomes 7 and 10 were not identified among the markers present in the leiomyosarcoma. All five tumours contained one or more abnormal chromosomes derived from chromosome 1. A Y chromosome was present in the leiomyosarcoma but in none of the carcinomas. PMID- 4018802 TI - A new syndrome in the group of euhidrotic ectodermal dysplasia. Pilodental dysplasia with refractive errors. AB - A new form of ectodermal dysplasia was observed in two siblings, offspring of healthy non-consanguineous parents. The main findings in both children are: hypodontia, abnormally shaped teeth, scalp hypotrichosis, pili annulati, follicular hyperkeratosis on the trunk and limbs, intensified delineation and reticular hyperpigmentation of the nape, and hyperopia; one of the siblings also has astigmatism. As both patients have normal nails and are euhidrotic, this is an ectodermal dysplasia of the pilodental subgroup. The cause is probably genetic and autosomal-recessive inheritance is most likely. PMID- 4018803 TI - Reciprocal balanced translocation of the long arm of chromosome 8 to the short arm of chromosome 7 in a woman with two spontaneous abortions. PMID- 4018804 TI - Susceptibility of different serovars of Chlamydia trachomatis to inactivation by normal human serum. AB - The ability of a panel of normal human serum samples to inactivate 12 strains of Chlamydia trachomatis, each of a different serovar, was investigated. A wide range of antichlamydial activity was observed, with survival rates of C trachomatis varying from less than 1% in some experiments to 100% in others. The strain specificity of the anti-chlamydial activity exhibited by individual serum samples was not, however, related to the antigenic cross reactivity between serovars demonstrable by microimmunofluorescence testing, which suggested that type specific antigens were not predominantly involved in the inactivation process. PMID- 4018805 TI - Pelvic inflammatory disease in patients infected with Chlamydia trachomatis: in vitro cell mediated immune response to chlamydial antigens. AB - Blood samples were obtained from 11 women with laparoscopically confirmed acute salpingitis who yielded positive cultures of Chlamydia trachomatis from the cervix. Four patients also had perihepatitis. Lymphocyte transformation assays, using C trachomatis serovars I and L2 as antigens, showed that the patients' lymphocytes responded to antigenic stimulation more strongly than the lymphocytes of age matched controls. Responses to the I and L2 antigens correlated strongly, but greater responses were obtained to the L2 antigen. No correlation was found between the response in the lymphocyte transformation assay and the degree of the inflammatory changes of the fallopian tubes, the presence of perihepatitis, or the titres of humoral antibodies to C trachomatis as measured by microimmunofluorescence. Sequential transformation assays, however, showed that patients with perihepatitis tended to have a more sustained response. PMID- 4018806 TI - Seroepidemiological survey of chlamydial genital infections in Khartoum, Sudan. AB - A total of 494 patients (90 men and 404 women) attending a sexually transmitted diseases (STDs) clinic in Khartoum, Sudan, were studied to assess the prevalence of chlamydial genital infections. Antibodies to Chlamydia trachomatis serotypes D to K were found in four (4.4%) men and 42 (10.4%) women, and 10 (2.5%) women had antibodies to serotypes A to C. PMID- 4018807 TI - Pivampicillin in treating genital infection with Chlamydia trachomatis. AB - Pivampicillin was used to treat urogenital colonisation with Chlamydia trachomatis in 41 women and 24 men who yielded chlamydiae but not gonococci. They were treated for 10 days. All but one patient gave negative chlamydia cultures 10 days after the start of treatment, and all 65 patients gave negative results at the second examination seven days later. Ten days of treatment with pivampicillin seems to be the optimum to eradicate C trachomatis from the lower genital tract in man. PMID- 4018809 TI - Effect of glare on performance of a VDT reading-comprehension task. PMID- 4018808 TI - Psychosocial impact of chronic infection with hepatitis B virus on British patients. AB - The effects of chronic infection with hepatitis B virus (HBV) on the lives of 40 British patients were studied by means of a questionnaire. The aspects considered were: social, sexual, and family life, physical and psychological health, and work. Thirty six patients considered their lives to have been affected, nine mildly, 14 moderately, and 13 severely. The aspects of life most affected were: sexual (13), psychological (11), physical (5), work (3), social (2), and family (2). Most of the problems encountered were related to infectivity. The availability of vaccines against HBV and of successful antiviral treatment have solved some of the problems, but it remains important for the medical profession to be aware of the multifaceted impact of the carriage of HBV. PMID- 4018810 TI - Studies on ergonomically designed alphanumeric keyboards. PMID- 4018811 TI - Posture, postural discomfort, and performance. PMID- 4018812 TI - Effects of rest and secondary task on simulated truck-driving task performance. PMID- 4018813 TI - Repeated measurements of spatial ability with the Manikin Test. PMID- 4018814 TI - Tunnel vision induced by a foveal load manipulation. PMID- 4018815 TI - Identification of oenanthotoxin and related compounds in hemlock water dropwort poisoning. AB - The case histories are presented of three separate incidents of poisoning by ingestion of Hemlock Water Dropwort tubers (Oenanthe crocata). Two of these cases involved a fatality. An analytical profile is provided for oenanthotoxin, the major toxic principal of the tubers. Chromatographic, spectroscopic and mass spectral data for related compounds are also given. PMID- 4018816 TI - Effects of retinoids on human lymphocyte functions in vitro. AB - E-Rosette formation in vitro, lymphocyte mitogenesis and natural killer (NK) activity of human blood lymphocytes were strongly inhibited by high concentration (10(-4) M) of retinol or retinal. Other retinoids at 10(-4) M (retinoic acid and 13-cis-retinoic acid) and lower concentrations (10(-7) or 10(-9) M) of retinol, retinal and carotenes also inhibited E-rosette formation. Lymphocyte transformation responses induced by concanavalin A (Con A) or pokeweed mitogen (PWM) were also inhibited while NK activity was not affected. There was a remarkable depression of the total number of viable lymphocytes after incubation with retinol or retinal 10(-4) M. However, other retinoids, 10(-7) and 10(-9) M of retinol and retinal and carotenes did not show marked decrease of lymphocyte number or viability even after prolonged incubation (48 h). The mechanism of inhibition by retinol or retinal (10(-4) M) is due in part to the decrease of viable lymphocytes. It is unclear how other retinoids, carotenes and lower concentrations (10(-7) or 10(-9) M) of retinol or retinal inhibit E-rosette formation or lymphocyte transformation. PMID- 4018817 TI - Antipyrine metabolism in African villagers. AB - Antipyrine clearance has been measured from serial serum samples in 49 healthy black Africans from a village in Southern Africa. The subjects follow a lifestyle which minimally exposes them to environmental inducing or inhibiting agents. Food is mainly maize cereal with a protein content of only about 8.8%, together with greens. Antipyrine clearance, half-life and apparent volume of distribution (mean +/- SD) were, respectively, 0.538 +/- 0.163 ml min-1, kg-1, 14.81 +/- 6.5 h and 0.626 +/- 0.075 litre/kg. These results do not differ significantly from the mean values found in a group of lactovegetarian Indo-Pakistani immigrants to Britain. This would suggest that the major environmental determinant influencing hepatic mixed-function oxidase activity is the presence or absence of meat in the diet. However, the relative contributions of environment and heredity will be difficult to determine. PMID- 4018818 TI - Paracetamol metabolism in African villagers. AB - Paracetamol clearance has been measured from serial serum samples in 49 healthy black Africans from a village in Southern Africa. The subjects are minimally exposed to known environmental inducing or inhibiting agents and the staple diet consists of maize cereal and greens. The mean clearance (+/- SD) was 4.98 +/- 1.61 ml min-1 kg-1, which is significantly faster than the values found in previous investigations with paracetamol in whites and Asian immigrants in London. The mean half-lives were fairly similar but the apparent volumes of distribution were also found to be larger in the present study. The ethnic difference in paracetamol kinetics identified in this study is possibly genetically controlled. PMID- 4018819 TI - Digoxin and cimetidine: investigation of the potential for a drug interaction. AB - The potential for a pharmacokinetic interaction between digoxin and cimetidine was investigated in a series of studies. In a single-dose cross-over study in healthy volunteer subjects cimetidine increased the area under the plasma digoxin concentration curve and the peak plasma digoxin concentration. In a repeated-dose study in healthy volunteer subjects taking digoxin 0.25 mg daily, co administration of cimetidine resulted in an average increase in plasma digoxin concentration of 0.15 ng/ml. In a repeated-dose study in healthy volunteer subjects taking digoxin 0.5 mg daily, co-administration of cimetidine resulted in an average increase in plasma digoxin concentration of 0.19 ng/ml. In a repeated dose study in patients receiving long-term digoxin therapy for atrial fibrillation co-administration of cimetidine had no significant effect on plasma digoxin concentrations. We have shown that co-administration of cimetidine and digoxin in volunteer subjects causes a statistically significant but small increase in plasma digoxin concentration but no such increase was found in patients. We conclude that it is doubtful that this interaction is of any clinical significance. PMID- 4018820 TI - Effects of meals and meal times on uptake of lead from the gastrointestinal tract in humans. AB - Twenty three adults ingested 203Pb as lead acetate on the 12th hour of a 19 h fast. Retention measured 7 days later in a whole-body counter was 61% and whole body turnover rates suggested that initial uptake had been considerably greater. Balanced meals eaten with 203Pb reduced lead uptake to 4% and the influence of the food lasted for up to 3 h. The effects of phytate, ethylene-diaminetetra acetate (EDTA), caffeine, alcohol, glucose, a liquid meal and a light snack were tested separately with intermediate results. The effect of a meal was probably largely due to its content of calcium and phosphate salts but lead uptake was probably further reduced by phytate which is plentiful in whole cereals and it was probably increased by a factor in milk. Uptake with skimmed milk was the same as with whole milk and we suggested that the factor was not fat. Comestibles with low mineral and phytate contents reduced lead uptake by intermediate amounts, possibly by stimulation of digestive secretions. The avid uptake of lead during a fast, the large reduction of lead uptake with meals and the likelihood of variations in gastric-emptying rates and dietary habits may be major causes of variation in body burdens of lead in the population. PMID- 4018821 TI - Pathways of Cr (III) and Cr (VI) in the rat after intratracheal administration. AB - 51Cr-labelled Cr3+ and CrO2-4 solutions were administered intratracheally to male rats in doses of 0.1 and 10 micrograms of Cr per rat to evidentiate metabolic differences especially in the lung and in the mechanisms of excretion. Twenty four hours after administration the highest 51Cr amount was present in the lungs for both valency states, being in the Cr (III)-treated group, however, about two times higher. In all other tissues tested the values in the Cr (VI)-treated animals were much higher. Intracellularly, in the Cr (III)-treated group more than 40% of the total lung homogenate was found in the nuclear fraction and only 10% in the cytosol. In the Cr (VI)-treated group 25% was present in the nuclei and more than 50% in the cytosol. Gel filtration 24 h after intratracheal injection showed that in both cytosols chromium was eluted in three peaks including a low-molecular-weight component. Quantitatively, however, the ratios between the 51Cr associated with the three peaks were significantly different between the Cr (III)- and the Cr (VI)-treated animals. This suggests that binding of chromium to low-molecular-weight components should be involved in the passage of this element from the lung to the other tissues. Excretion studies for 7 days showed that after this time the Cr (III)-treated animals excreted about 4% of the dose via urine and more than 36% via faeces, whereas in the Cr (VI)-treated rats the 51Cr was eliminated nearly equally between urine and faeces. PMID- 4018822 TI - Discolouration of the optic disc in baboons during treatment with prizidilol (SK&F 92657), a novel antihypertensive agent. AB - Prizidilol (SK&F 92657-A2 X H2O) is the dihydrochloride salt of D,L-3-[2-(3-t butylamino-2-hydroxypropoxy)phenyl]-6-hydrazinopyridazi ne, a molecule combining the properties of precapillary vasodilatation and beta-adrenoceptor blockade. Prizidilol was administered to baboons daily for up to 1 year at sustained doses up to 800 mg/kg. During the 16th week of a 26-week study ophthalmoscopic examination revealed an orange tinge at the periphery of the normally pale pink optic disc in all high-dose (800-1225 mg/kg) baboons. The colour became more intense as the study progressed. By week 25 orange discolouration was seen in all baboons at 350 mg/kg and three out of six baboons at 100 mg/kg. The findings, except those at 100 mg/kg, were confirmed in a 12-month study. Optic disc discolouration was correlated with darkening of internal organs at necropsy. Discolouration of the optic disc did not appear to affect visual function. Slow regression of discolouration was demonstrated after withdrawal of treatment with 800 mg of prizidilol/kg at 6 months. No histological abnormalities were present in the optic discs of affected baboons. The study demonstrates the value of regular ophthalmoscopy in toxicity studies, combining the facility for the early detection of an unusual lesion with the ability to follow its time-course. PMID- 4018823 TI - Kinetic aspects of misonidazole and its major metabolite in radiotherapy. AB - Oral doses of misonidazole between 0.75 and 1.3 g/m2 were administered during 3-5 days per week to 21 patients with various malignancies. Mean plasma levels of misonidazole and desmethylmisonidazole at the times of radiotherapy were in the range 20-50 and 2-12 mg/l respectively. Slight accumulation of misonidazole and desmethylmisonidazole in plasma was observed with a dosage interval of 24 h. In patients with anticonvulsant comedication plasma elimination half-lives of misonidazole of 4.1-8.9 h were found. Observed side-effects were nausea and vomiting (9%), exanthema or rashes (14%) and mild peripheral neuropathy (9%). PMID- 4018824 TI - Organochlorine pesticide residues in human fat in the United Kingdom 1982-1983. AB - Between December 1982 and October 1983 samples of human body fat were taken during routine necropsies carried out on 187 persons aged over 5 years and four infants aged under 4 months. Comparison of the results of analysis with those from the previous studies in 1976-1977, and earlier, shows a continuing decline in residues of p,p'-dichlorodiphenyltrichloroethane (p,p'-DDT) and dieldrin (HEOD) and a reduction in the amounts of p,p'-dichlorodiphenyltichloroethane [p,p'-DDE, a metabolite of p,p'-DDT] and hexachlorobenzene. The concentrations of other compounds were similar to those observed in the previous studies. The results show that the amounts of organochlorine pesticides and polychlorobiphenyl compounds contained in human fat samples from residents in the UK compare favourably with data obtained in other countries. PMID- 4018825 TI - A toxicology databank based on animal safety evaluation studies of pharmaceutical compounds. AB - Thirteen UK pharmaceutical companies have provided comprehensive toxicological data from repeated-dose animal safety evaluation studies of 74 pharmaceutical compounds. These data comprise a unique toxicology database and this paper describes its establishment including the problems encountered, its current size with over 35 000 data fields, its content and potential value for retrospective analyses. Increasing reliance on animal studies for predicting the safety of medicines in man necessitates a reappraisal of conventional animal testing procedures and better use of the considerable volume of data in the archives of regulatory authorities and pharmaceutical companies. This reappraisal may be achieved by the use of computer-based toxicology databanks. PMID- 4018826 TI - Screening the in vitro sperm-immobilizing effect of some anticancer drugs. AB - The in vitro sperm-immobilizing effect of seven anticancer agents, namely cyclophosphamide, 5-fluorouracil, cytarabine, mitomycin-C, 6-mercaptopurine, doxorubicin and vinblastine were screened with a transmembrane migration method. Only doxorubicin and vinblastine inhibited human sperm motility. Because colchicine, a microtubular inhibitor, had no sperm-immobilizing effect, we suggest that the sperm membrane is the site of action of these two anticancer drugs to inhibit human sperm motility. PMID- 4018827 TI - Electrocutaneous communication in a guide dog robot (MELDOG). PMID- 4018828 TI - A polynomial method for fitting continuous distributions of exponentials with positivity constraint. PMID- 4018829 TI - Single microelectrode analysis of electrically coupled networks. PMID- 4018830 TI - Laser-induced fabrication of a transsubstrate microelectrode array and its neurophysiological performance. PMID- 4018831 TI - Estimation of local cardiac wall deformation and regional wall stress from biplane coronary cineangiograms. PMID- 4018832 TI - Classification of heart tissue from bipolar and unipolar intramural potentials. PMID- 4018833 TI - Diffraction and dispersion effects on the estimation of ultrasound attenuation and velocity in biological tissues. PMID- 4018834 TI - Calculation of zero-crossing and spin-lattice relaxation time pictures in inversion recovery NMR imaging. PMID- 4018835 TI - Coupling efficiency of helical coil hyperthermia applications. PMID- 4018836 TI - Genetically determined resistance to listeriosis is associated with increased accumulation of inflammatory neutrophils and macrophages which have enhanced listericidal activity. AB - The C57BL/6 and A/J inbred strains of mice differ markedly in their resistance to the facultative intracellular bacterium Listeria monocytogenes. One possible explanation for this genetically determined resistance is that phagocytes from Listeria-resistant strains of mice can kill L. monocytogenes more effectively than phagocytes from Listeria-susceptible strains of mice. We report here that inflammatory neutrophils and macrophages from Listeria-resistant mice (C57BL/6) exhibit a slight but significantly enhanced ability to kill L. monocytogenes in vitro as compared to inflammatory phagocytes from Listeria-susceptible mice (A/J). More importantly, however, Listeria-resistant mice recruited more inflammatory neutrophils and macrophages to the peritoneal cavity in response to i.p. injection of heat-killed Listeria than did Listeria-susceptible mice. These data suggest that genetically determined resistance to listeriosis is dependent on the enhanced inflammatory responsiveness of Listeria-resistant mice. Further support for this hypothesis was provided by experiments in which the passive transfer to A/J mice (C5-deficient) of plasma from C57BL/6 mice (C5-sufficient) enhanced the ability of the recipient A/J mice both to recruit inflammatory neutrophils to the peritoneal cavity in response to i.p. injection of heat-killed Listeria, and to clear L. monocytogenes from the spleen after a sublethal challenge of viable Listeria. PMID- 4018837 TI - Origin and immunological hyporeactivity of canine alveolar lymphocytes. AB - Autochthonous canine thoracic duct lymphocytes were isolated, labelled with 111indium and injected intravenously. Direct sampling showed that the label passed from blood to lymph within 25 hr. By gamma camera imaging, the initial accumulation of 111In the liver and spleen was followed by a striking increase in lymph node associated activity between 24-36 hr. Although initial lung-associated counts were low, a bicarbonate-induced non-specific inflammation of the right lung induced a rapid and selective accumulation of labelled lymphocytes (ratio right to left lung 8:1). Cell suspensions lavaged from the alveolar surface showed only a 9% response to phytohaemagglutinin (PHA) compared to peripheral blood lymphocytes (PBL). The addition of unfractionated lavage cells to PBL caused a macrophage-dependent suppression of mitogen responsiveness. However, macrophage depletion of alveolar lavage cells did not restore the lymphocyte response to PHA. Similarly, the frequency of alloreactive precursors of cytolytic lymphocytes (CTL) was almost 10-fold less in alveolar lymphocytes compared to PBL. Thus, bronchoalveolar lavage provides a technique by which viable cells may be recovered in significant numbers from the alveoli and should be invaluable for the investigation of lung allograft rejection. PMID- 4018838 TI - A comparative study on the internal defence system of juvenile and adult Lymnaea stagnalis. AB - The immunological immaturity of juvenile specimens of some snail species, e.g. Lymnaea stagnalis, may contribute to their greater susceptibility to infection by schistosome parasites. In a comparison between juvenile and adult specimens of the pond snail L. stagnalis, we have shown that the blood cells (amoebocytes) of juvenile snails are less efficient at phagocytosing: fewer amoebocytes are competent and the average number of particles engulfed per cell is lower. This functional immaturity seems to correlate with morphological immaturity of the amoebocytes. Opsonic and haemagglutinating activities are low in juvenile snail plasma, but much higher in adult plasma. Finally, however, the initial rate at which injected bacteria are eliminated from the circulation seems only slightly slower in juvenile snails than it is in adults. PMID- 4018839 TI - Reduction of the complement activation capacity of soluble IgG aggregates and immune complexes by IgM-rheumatoid factor. AB - The influence of IgM-rheumatoid factor (IgM-RF) on the activation of isolated C1 by soluble IgG aggregates (AIgG) and immune complexes was studied. IgM preparations obtained from the sera of four patients with seropositive rheumatoid arthritis markedly reduced the C1 activation capacity of AIgG, especially when large aggregates were tested. The results of parallel experiments with radiolabelled AIgG indicated that this inhibitory effect of IgM-RF was accompanied by a very large increase of the aggregate size. A comparable IgM preparation isolated from pooled normal human serum influenced neither the size nor the C1 activation capacity of AIgG. The inhibitory effect of IgM-RF on C1 activation was also demonstrated for soluble tetanus-anti-tetanus immune complexes. Thus, in spite of the established C activation ability of IgM-RF and the fact that, in general, larger IgG aggregates and immune complexes activate C1 more efficiently, cross-linking and size enlargement of soluble IgG complexes and aggregates by IgM-RF lead to a decrease of the C1 activation capacity. As a consequence, IgM-RF may reduce plasma complement activation by soluble IgG complexes in the circulation of patients with seropositive rheumatic diseases. PMID- 4018840 TI - The IgG4 subclass is associated with a low affinity antibody response to tetanus toxoid in man. AB - The amount and relative affinity of antibodies to tetanus toxoid were measured, following immunization, in patients with chronic or recurrent acute chest infections and in healthy controls. The responding patients and controls produced similar amounts of antibody and, although antibody affinity was higher in the controls compared to the patients, the differences were not significant. Most individuals (65%) produced antibody of the IgG1 subclass with little or no IgG4 antibody, but in the remainder antibody was either predominantly IgG4 (29%) or equally distributed between the IgG1 and IgG4 subclasses (6%). Antibody affinity was significantly lower in both patients and controls producing IgG4 antibodies compared to those with a predominantly IgG1 response, and antibody affinity increased with the amount of IgG1 antibody present. These results provide preliminary evidence of an association between low antibody affinity and the IgG4 subclass in man. PMID- 4018841 TI - Immunoglobulin D in rat serum, saliva and milk. AB - Previously, this laboratory has found very high concentrations of IgD in normal rat milk. Using ELISA methods, the relationship between milk, serum and saliva IgD in lactating and suckling rats was examined. Milk IgD appears to be synthesized in the mammary tissue rather than taken up from the blood because (i) serum IgD remains low and is not significantly different from that of non lactating females, and (ii) serum IgD during lactation is poorly correlated with milk IgD. Serum IgD in suckling rats declines in the first 7 days following birth and remains relatively low during the remainder of lactation (2-4 micrograms/ml). The surprisingly high serum IgD observed at birth (9.3 +/- 3.2 micrograms/ml) is present before suckling begins and is not affected by the onset of suckling. Transient elevations of serum IgD begin to occur following weaning. Rats weaned 10 days earlier than normal (Day 20 vs Day 30) had significantly higher serum IgD on Days 36, 47 and 60. Among 43 adult rats, serum IgD was 5.4 +/- 3.6 micrograms/ml and saliva IgD 2.0 +/- 1.7 micrograms/ml. Serum IgD correlates poorly with saliva IgD. The thymus is not required for IgD synthesis since no significant difference in serum IgD was found between nude rats and their euthymic littermates. PMID- 4018842 TI - IgA antibodies in rat bile inhibit cholera toxin-induced secretion in ileal loops in situ. AB - The biological actions of IgA antibodies in bile are largely undefined. We therefore tested whether biliary IgA antibodies could specifically inhibit cholera enterotoxin (CT)-induced secretion in the rat ileum. Rats were immunized by CT given orally or by injection into Peyer's patches. Bile was collected by bile duct cannulation, and anti-CT antibodies in the bile were measured by ELISA. CT plus bile from either immunized or unimmunized rats, or CT plus anti-CT containing bile which had been absorbed by a CT immunosorbent, were instilled into in situ ileal loops in unimmunized rats; CT alone, or buffer was instilled into other loops. The bile used from the immunized rats contained IgA, but neither IgG nor IgM, anti-CT antibodies. It was found that bile containing IgA anti-CT antibodies almost totally inhibited the secretory effect of CT, and this inhibition was abrogated by absorption of the IgA anti-CT antibodies. Thus, IgA antibodies to an enterotoxin, secreted into bile, are effective against the enterotoxin in the rat intestine in vivo. PMID- 4018843 TI - Hepatic uptake of circulating IgG immune complexes. AB - IgG antibodies were found to increase the uptake of circulating dinintrophenylated human serum albumin (DNP-HSA) preparations by the nonparenchymal liver cells in rats. Highly DNP-conjugated HSA was taken up by the Kupffer cells both when given alone and when complexed by IgG. More lightly DNP conjugated HSA was taken up mainly by the liver endothelial cells. Here, IgG promoted the antigen uptake both by the Kupffer cells and by the endothelial cells. Uptake of IgG immune complexes (IgG-ICs) by the sinusoidal endothelial cells of the liver is a new aspect on the function of these cells. Whether or not this phenomenon is Fc receptor-mediated is discussed. A heat-labile serum factor was found to direct the ICs to the Kupffer cells. This implies that serum complement and hepatic C3 receptors are essential for the physiological clearance of circulating immune complexes. PMID- 4018844 TI - Effect of FUT-175, a new synthetic protease inhibitor, on the development of lupus nephritis in (NZB x NZW) F1 mice. AB - FUT-175 (6-amidino-2-naphthyl p-guanidinobenzoate dimethanesulphonate), a new synthetic protease inhibitor, was administrated to (NZB x NZB) F1 mice in order to examine its influence on the development of autoimmune diseases. A dose (400 mg/kg of body weight) of FUT-175 has both prophylactic and curative effects on the development of lupus nephritis: mice showed a significantly low percentage of proteinuria, a marked decrease in BUN levels, and the lowest degree of glomerular damages. Dexamethasone had almost the same effect as FUT-175 (400 mg/kg), but it was slightly less effective than FUT-175. These results suggest that the administration of FUT-175 may become a viable strategy for the treatment of human autoimmune diseases. PMID- 4018845 TI - Regulation of human natural killing by lysosomotropic and thiol-reactive agents. AB - Treatment of human peripheral blood lymphocytes (PBL) with ammonium or other lysosomotropic amines eliminates natural killing (NK) activity of effector cells without affecting their viability. Inhibition of NK by these reagents is probably due to blocking of events subsequent to effector cell target cell binding but before programming for cytolysis. Treatment of K562 target cells with the same reagents has no effect on target cell sensitivity to NK. Pretreatment of effector cells with the NK inhibitory lysosomotropic agents decreases lysosomal thiol cathepsin activity without affecting the lysosomal acid phosphatase activity. Thiol-reactive agents, tosyl-L-lysine chloromethyl ketone (TLCK) and iodoacetamide also inhibit NK and thiol cathepsin activity in PBL. These data suggest a role for thiol-containing enzymes in the early stages of NK cytolysis. PMID- 4018846 TI - The role of shed Fc receptor in the regulation of lymphocyte response to phytohaemagglutinin (PHA). AB - Supernatants from 18-hr cultures of human peripheral blood polymorphonuclear cells (PMN) and adherent cells (AC) inhibited the binding of erythrocyte-antibody complexes (EA) by PMN. The inhibitory activity was lost upon absorption on IgG and Fc, but not on the F(ab')2 fragment of IgG. IgG-binding material (shed Fc receptor--FcR) was reutilized by PMN and AC which had lost their own FcR in vitro. Reutilization was independent of the type of cells from which FcR originated. The FcR-containing material eluted from IgG-coated Sepharose column inhibited PHA-induced lymphoproliferation, probably via prior interaction with monocytes. These results suggest that shed FcR may be freely exchanged between different types of human leucocytes and play a role in the suppression of mitogen induced T-cell responses. PMID- 4018847 TI - Effect of stilboestrol on adrenal steroidogenesis in albino rats. PMID- 4018848 TI - Effect of verapamil, nifedipine and diltiazem on experimental myocardial infarction in rats. PMID- 4018849 TI - Effect of cigarette smoke inhalation on certain pulmonary and hepatic drug metabolizing enzymes in rat and mouse. PMID- 4018850 TI - Effect of alloxan induced diabetes on 125I-insulin receptor interaction and 14C glucose/14C-galactose homeostasis in isolated rat hepatocytes. PMID- 4018851 TI - Use of indirect haemagglutination test to detect humoral antibodies of orf disease. PMID- 4018852 TI - A structural somatic variant of the Kk antigen is generated by point mutation. AB - We have previously selected structural variants of the Kk antigen from a (C3 X D2)F1 T-cell lymphoma. Those mutants were identified by the loss of certain epitopes defined by monoclonal antibodies. The variant Kk molecule from HK13.S3 cells is no longer recognized by 40% of the trinitrophenyl-specific, Kk restricted cytotoxic T lymphocytes. Here we report on the primary structure of the altered Kk molecules from the cell line HK13.S3. Comparison with the parental Kk reveals a single base pair exchange, GCG to GTG, that results in an alanine to valine exchange in position 40 of the protein. This observation emphasizes that minor structural alterations in class I molecules may have a strong effect on the H-2-restricted T-cell response. PMID- 4018853 TI - Definitive chromosomal location of the H-2 complex by in situ hybridization to pachytene chromosomes. AB - Chromosome 17 of the mouse carries the H-2 complex and the T/t complex. An understanding of the organization of this region and an accurate genetic map of chromosome 17 would be of great value for both immunologists and developmental biologists. Until now the only maps available have been derived solely from recombinational studies using several translocations, an inherently inaccurate method. We have found the definitive location of the H-2 complex by the use of in situ hybridization. Our results show that both the T/t complex and the H-2 complex map to positions far more distal than the generally accepted map positions. This proves that recombination in Robertsonian chromosomes underestimates physical map distances on chromosome 17. PMID- 4018855 TI - Evidence for recurrent infection & intra-familial spread of enterovirus-70 conjunctivitis during post-epidemic period. PMID- 4018856 TI - Transovarial transmission of Japanese encephalitis virus in Culex bitaeniorhynchus mosquitoes. PMID- 4018854 TI - Lack of Fc receptor for IgE in SJA9 mice. PMID- 4018857 TI - Immune reactions to exsheathed microfilariae of Litomosoides carinii. PMID- 4018858 TI - Effect of early maternal deprivation on brain 5-HT & pentobarbitone sleeping time in suckling rats. PMID- 4018859 TI - Circulating thyroid hormone levels in rheumatoid arthritis--a preliminary communication. PMID- 4018860 TI - Serological evidence for rheumatic fever & rheumatic heart disease in Kashmir (India). PMID- 4018861 TI - Use of BCG or levamisole as an adjunct to chemotherapy or radiotherapy in malignant lymphomas. PMID- 4018862 TI - Simultaneous measurement of gastric-small intestine motility & absorption of proline in rats exposed to heat. PMID- 4018863 TI - A new subtype of Salmonella subgenus II (S. II 11: a: 1, 5) from India. PMID- 4018864 TI - Biotype characterization & antibiotic sensitivity of campylobacters from human & non-human sources in Calcutta. PMID- 4018865 TI - Field trials on the relative efficacy of five repellents against Simulium himalayense (Diptera:Simuliidae). PMID- 4018866 TI - Modulation of host immune responses by metronidazole. PMID- 4018867 TI - Lack of circadian rhythmicity in serum prolactin in traumatic tetraplegics during the spinal shock phase. PMID- 4018868 TI - Pathology of acute renal failure & haemolytic uraemic syndrome in acute dysentery in children. PMID- 4018869 TI - Unusual features of haemoglobin-E thalassaemia. PMID- 4018870 TI - Effect of lesions of striatum on lordosis behaviour in female rats. PMID- 4018871 TI - Hypoglycemic activity of Tephrosea purpurea Linn. seeds. PMID- 4018872 TI - Comparison of proportions based on the same or paired subjects. PMID- 4018873 TI - Marked enhancement in vivo of adjuvant activity of muramyl dipeptide to protein antigens and to synthetic weak immunogens with monoclonal anti-muramyl dipeptide antibodies. AB - Priming of mice with complexes of antigen coupled to muramyl dipeptide and monoclonal anti-muramyl dipeptide antibodies enhanced the adjuvant activity of muramyl dipeptide on the humoral response to the antigen. The enhancement did not occur with free (uncoupled) muramyl dipeptide and required the presence of an adjuvant-active hapten within the complex as well as the Fc fragment of the monoclonal antibody. This system proved highly effective in eliciting antibodies to synthetic weak immunogens whereas muramyl dipeptide, on its own, exerts very little or no adjuvant activity. The effect was not due to a general polyclonal activation and was restricted to the antigen coupled to the synthetic adjuvant. Possible pathways involved in this phenomenon are discussed. PMID- 4018874 TI - Characterization of the metabolism inhibition antigen of Mycoplasma arthritidis. AB - The Mycoplasma arthritidis antigen(s) responsible for eliciting metabolism inhibiting antibodies in rabbits has been partially characterized. Metabolism inhibiting activity was absorbed from rabbit antisera by intact M. arthritidis cells and membranes but much less so by the soluble cytoplasmic fraction, indicating that the antigen is located on the outer membrane surface. It was stable to periodate and lipid extraction but labile to heat and proteolytic enzymes, indicating that it is protein in nature. Finally, it is most likely a tightly bound integral rather than a peripheral membrane protein, since it was not extracted by low-ionic-strength solutions or by the nonionic detergents Triton X-100, Nonidet P-40, and Tween 20. It was solubilized by both the anionic agent sodium deoxycholate and the zwitterionic detergent Zwittergent. Two two monoclonal antibodies with metabolism-inhibiting activity were produced. One recognized a 45,000-dalton surface protein; however, the other recognized an antigen which is probably of cytoplasmic origin, indicating that more than one cell component may be involved in the metabolism-inhibiting antibody response. PMID- 4018875 TI - Ultrastructural studies of adherence of Staphylococcus aureus in experimental acute hematogenous osteomyelitis. AB - A model of acute hematogenous osteomyelitis initiated by injection of Staphylococcus aureus into 29-day-old chickens was used. Transmission electron microscopy showed that the bacteria adhered to exposed cartilage matrix in the metaphyseal region of long bones but not to adjacent vascular linings or to erythrocytes. It is proposed that the combination of exposure of growth plate cartilage during normal bone growth and the ability of S. aureus to adhere to this cartilage is the mechanism for initiation of infection which proceeds to an osteomyelitic abscess. PMID- 4018876 TI - Relationship between delayed hypersensitivity response and acquired cell-mediated immunity in C57BL/6J mice infected with Leishmania donovani. AB - The relationship between the development of acquired cell-mediated immunity and the concomitant level of specific delayed hypersensitivity (DH) in C57BL/6J mice infected with the intracellular protozoan parasite Leishmania donovani was studied. It was determined that the intradermal injection of Leishmania antigen (heat- or phenol-killed flagellated forms of L. donovani) could elicit a DH response as early as day 10 and as late as day 120 postinfection in mice infected by the intravenous route. Dose-response studies showed that there is an inverse relationship between the size of the infecting dose of parasites and the magnitude of the DH response. Thus, increasing the degree of infection depressed the DH response. This depression, however, could be abrogated by treatment of mice with cyclophosphamide (201 mg/kg) before intradermal injection of antigen. PMID- 4018877 TI - First aid for cage birds. PMID- 4018878 TI - Anal and perianal surgery in dogs and cats. PMID- 4018879 TI - Intra-articular anaesthesia of the equine hock. PMID- 4018880 TI - Copper deficiency in cattle and sheep. PMID- 4018881 TI - Binding and uptake of mercuric chloride in human lymphoid cells. AB - Animal and human lymphoid cells are stimulated in their DNA synthesis by mercuric chloride. A direct binding of labelled mercuric chloride (203HgCl2) to the membranes of human thymocytes and peripheral blood lymphocytes could be demonstrated as early as 15 min after isotope addition. There was also an uptake of mercury in the nuclei, as determined by liquid scintillation. The isotope activity was recovered in the phenol-soluble nuclear fraction, i.e. containing non-histone phosphoproteins. PMID- 4018883 TI - Regulatory effect of hydrocortisone on the in vitro synthesis of IgE by human lymphocytes. AB - The effect of different concentrations of hydrocortisone (HC) on the in vitro, pokeweed mitogen-driven synthesis of IgG and IgE by human lymphocytes was studied. HC had the same modulatory action on the production of both immunoglobulins. Two different effects were observed: the first is enhancement of Ig synthesis by low concentrations of HC (10(-7)-10(-4) M), and the second is inhibition of synthesis by higher concentrations due to lymphocytotoxic effect. PMID- 4018882 TI - Adjuvant activity of saponin: antigen localization studies. AB - The adjuvant saponin potentiates the antibody response of mice to the antigen keyhole limpet hemocyanin (KLH). Studies using 125I-labelled KLH show that saponin significantly prolongs the retention of antigen at the subcutaneous injection site and also increases the amount reaching the spleen. Both these phenomena were associated with the inflammatory response to saponin and were markedly reduced following abolition of the inflammatory action of saponin by addition of cholesterol-containing liposomes. The adjuvant action of saponin was not modified by this treatment. Further evidence that neither antigen retention nor splenic localization is implicated in the adjuvant action of saponin for KLH is the demonstration that digitonin, which shares hemolytic and cholesterol binding activity with saponin, caused similar antigen retention and splenic localization but was not adjuvant active. PMID- 4018885 TI - HLA and lymphocyte histamine sensitivity in mastocytosis. AB - HLA-ABC and DR typing was performed on 50 patients with mastocytosis. Lymphocyte stimulation with concanavalin A has earlier been performed in 22 of these patients. No phenotypic aberrations were detected in the patient group. 8 patients had the HLA-B12 phenotype. Lymphocytes from the HLA-B12 phenotype stimulated with a lymphocyte mitogen have earlier been shown to react with decreased inhibitory effect to histamine. 2 patients in this study had the HLA B12 phenotype and systemic mastocytosis with high histamine turnover, but these patients reacted with a low mitogen response of the lymphocytes. PMID- 4018884 TI - Humoral immunity to dietary antigens in healthy adults. Occurrence, isotype and IgG subclass distribution of serum antibodies to protein antigens. AB - The occurrence of antibodies to five dietary protein antigens in the sera from 21 healthy adults was investigated by a modified Farr assay. Antibody to ovalbumin (OA) occurred most frequently (90%) whereas only 24% had antibodies to alpha lactalbumin (ALA). No correlation was noted between the titer of antibodies against bovine serum albumin (BSA) and OA in the single individual. The avidity constants (10(8)-10(9) l/mol) and cross-reactivities against other albumins of anti-BSA antibodies in two human sera were comparable to that of the antibodies in pooled hyperimmune rabbit antiserum. Crossed radioimmunoelectrophoresis showed serum anti-BSA and anti-OA antibodies to be predominantly of the IgG class (13/13, 10/10), occasionally of the IgA- (6/13, 1/10) and rarely of the IgM class (1/13, 0/10). Analysis by radioelectroimmunoassay (rocket immunoelectrophoresis) of the IgG subclass distribution of anti-BSA and anti-OA antibodies showed total absence of IgG3. In contrast, antibodies of the IgG4 subclass were frequently present even in sera with very low levels of total IgG4. PMID- 4018886 TI - Cross reactivity studies with platinum group metal salts in platinum-sensitised rats. AB - Hooded Lister rats were sensitised to the halide salt of platinum ammonium tetrachloroplatinate(II)[(NH4)2PtCl4] in its conjugated form with ovalbumin. Sensitisation was achieved by intraperitoneal injection with Bordetella pertussis vaccine as adjuvant, followed 21 days later by a further injection in saline. The presence of specific anti-platinum IgE antibody was determined by passive cutaneous anaphylaxis (PCA) and radioallergosorbent test (RAST) using the platinum halide salt conjugated to a heterologous carrier. Sera exhibiting positive reactions were pooled and PCA tests performed on the titrated pooled sera with 3 conjugated platinum group metal salts, 5 platinum group metals in their free salt form and 6 platinum salts with differing ligands. PCA challenges with these compounds resulted in significant cross reactivity between ammonium tetrachloroplatinate(II), ammonium hexachloroplatinate(IV) and the conjugated tetrachloroplatinate. There was very limited cross reactivity with other platinum or platinum group metal salts in either free or conjugated forms. Furthermore, these results were confirmed by RAST inhibition studies. PMID- 4018887 TI - Ultrastructural categorization of human sperm cryopreserved in glycerol and in TESTCY. AB - The motility of human sperm after thawing and the ultrastructural integrity of their acrosomal region was evaluated in 5 semen donors after utilizing 2 cyproprotective extenders--glycerol and TESTCY. Sperm motility in the fresh control semen fraction (65.5% +/- 6.1) was significantly (P less than 0.05) better than the immediate post-thaw motility in both cyprotected fractions (38.8% +/- 2.0 for glycerol and 31.0% +/- 2.9 for TESTCY), and there was no significant difference between the two cyprotective treatments. The overall % of normal intact sperm heads was significantly less than in controls (P less than 0.05) following cypropreservation in glycerol, but values for sperm stored in TESTCY were not significantly different from controls or glycerol. However, when expressed as % change from controls values, sperm preservation was significantly better (P less than 0.05) in TESTCY than in glycerol. TESTCY is considered a better cryoprotective agent for human sperm. PMID- 4018888 TI - The anti-glycolytic action of (S)-alpha-chlorohydrin on epididymal bovine spermatozoa in vitro. AB - (S)-alpha-Chlorohydrin interferes with glycolysis in bovine spermatozoa whereas the (R)-isomer is ineffective. The action of the (S)-isomer, which involves inhibition of the reaction catalysed by glyceraldehyde 3-phosphate dehydrogenase, is not immediate but is evident only after a brief period of incubation with the spermatozoa. This inhibitory action is prevented when glycerol is present suggesting that the mechanism of action of (S)-alpha-chlorohydrin requires its oxidation to (S)-3-chlorolactaldehyde which is the active metabolite. Addition of racemic 3-chlorolactaldehyde to bovine spermatozoa caused immediate inhibition of glycolysis. It is proposed that the action of (S)-alpha-chlorohydrin in bovine spermatozoa is similar to that observed in the spermatozoa of other species in being a two-stage process; first, its oxidation to (S)-3-chlorolactaldehyde, and then inhibition of the glycolytic enzyme by this metabolite. PMID- 4018889 TI - Nuclear chromatin decondensation of spermatozoa in vitro: a method for evaluating the fertilizing ability of ovine semen. AB - Spermatozoa obtained from testes, epididimydes and complete ejaculates of healthy rams during the breeding and non-breeding seasons were induced to show nuclear chromatin decondensation by controlled exposure to dithiotreitol (DTT) and sodium dodecyl sulphate (SDS) in vitro. A gradual resistance to decondensation was shown by sperm during epididymal transit, confirming a progressive increase in the prevalence of chromatinic disulphide bonds during sperm maturation in this species. A high % of stable (non-decondensed) sperm nuclei after treatment (79%) was found in semen from rams with normal fertility (64% non-return rate at first oestrus). Opposite changes were found in the semen from rams having low fertility rates (37%), as these showed only 31% of stable sperm nuclei. There were no differences in the spermiograms of these two groups. When semen from the same rams was tested during the non-breeding season, a similar relationship was found, although in both groups there was a higher % of sperm with stable nuclei than during the breeding season. The possible role of seminal plasma and of some of its constituents (e.g., zinc) on the decondensation of ram sperm nuclear chromatin was also studied. The presence of seminal plasma and the addition of zinc largely or completely inhibited the decondensation of ram sperm nuclear chromatin whilst the reverse situation was seen following the addition of chelating agents (e.g. EDTA) to the semen samples. The present results suggest that the induction of sperm nuclear decondensation by exposure to DTT and SDS under controlled conditions may provide a simple but reliable method for predicting in vitro the fertilizing ability of a ram semen sample. PMID- 4018890 TI - Prevention of hypo-osmotic swelling by detergents provides clues to the membrane structure of rat sperm. AB - The proportion of sperm from the caput epididymidis of the rat that swelled in hypo-osmotic media was reduced in a dose-dependent manner by detergents, with relative effectiveness as follows: CTAB greater than Digitonin greater than Hyamine 10-X greater than SDS greater than Triton X-100 greater than Deoxycholate. Polymyxin was a poor lytic agent, possibly because anionic lipids are in the inner leaflet of the membrane. Less digitonin was needed to lyse mature sperm from the distal cauda epididymidis, suggesting that there is less cholesterol in their membranes. PMID- 4018891 TI - Effect of intra-epididymal injection of copper particles on fertility, spermatogenesis, and tissue copper levels in rats. AB - In male rats, a single injection of 10 mg metallic copper particles in oil into each caput epididymidis induced infertility, whilst leaving mating behaviour and blood testosterone levels unchanged. Fertility tended to recover 5.5 months after the copper treatment. Although the copper content of the caput epididymidis reached a level of around 100 times higher than control values, the serum copper concentration did not rise significantly. This finding and the observation that treated animals gained weight as fast as the controls suggest a low systemic toxicity of this method. The testicular copper concentration was significantly higher than that in controls and different degrees of damage, including vacuolation, karyorrhexis, pyknosis, and cytolysis, were seen mainly in pachytene spermatocytes and early spermatids. Clumps of foreign particles, apparently metallic copper, were found in the interstices of the caput epididymidis together with degenerative changes in the epithelial cells of the caput, suggesting a possible effect of copper on the epididymal epithelium. The viability of epididymal sperm decreased more markedly than the decrease in sperm density. It is therefore most likely that the major cause of infertility after copper injection into the caput epididymidis is a direct inhibitory effect of copper on the sperm, whilst damage to the seminiferous and epididymal epithelial may contribute. PMID- 4018892 TI - Radiation-induced degradation of trichloroethylene and tetrachloroethylene in drinking water. AB - The gamma-radiation degradation of trace amounts (70-440 ppb) of trichloroethylene and tetrachloroethylene in drinking water has been investigated. The doses necessary to reduce the pollutant concentration to 1 ppb are in the order of 1 kGy. PMID- 4018893 TI - Chemical and biological properties of a cationic Tc-tetraamine complex. AB - The complex of 99Tc with the ligand 1,4,8,11-tetraazaundecane (2,3,2-tet) was prepared and was compared with the similar 99Tc complexes with ethylenediamine and 1,4,8,11-tetraazacyclotetradecane. The results are all consistent with the formula [TcO2(2,3,2-tet)]+. The biological behavior was tested with 99mTc in Wistar rats. A fast clearance via the kidneys was found, and no accumulation in any other organ was observed. PMID- 4018894 TI - Synthesis and some characteristics of no-carrier added [18F]fluorotrimethylsilane. AB - [18F]Fluorotrimethylsilane was prepared in 80% decay corrected yield by reaction of no-carrier added tetramethyl-ammonium fluoride (hydroxide as bulk anion) with chlorotrimethylsilane in 65% aqueous acetonitrile. The 18F gas was collected in a cold-trap at -130 degrees C and found to have an Ostwald solubility coefficient of 11.5 in paraffin oil. Accurate measurement of its aqueous solubility was precluded by hydrolysis. When rats were allowed to inhale [18F]fluorotrimethylsilane extensive uptake of 18F occurred in bone, demonstrating ready release of fluoride in vivo. PMID- 4018895 TI - An improved [18O]water target for [18F]fluoride production. PMID- 4018896 TI - A simple factor for the evaluation of the specific activity of radiopharmaceuticals. PMID- 4018897 TI - A feasibility study of the in vivo prompt gamma activation analysis using a mobile nuclear reactor. AB - A facility for in vivo prompt gamma activation analysis using moderated neutron beams from a 0.1 W mobile nuclear reactor is described. The low-power nuclear reactor provides total neutron flux of 3.3 X 10(4)n cm-2 s-1 on the surface of a vertical beam tube to which a liquid phantom is positioned. The capability of such a partial-body irradiation facility is demonstrated by measuring trace amounts of toxic cadmium in kidney. The detection limit of Cd in kidney for a skin dose of 1.66 mSv (166 mrem) is 1.34 mg under 500 s irradiation. This facility therefore combines the advantages of mobility with high sensitivity of detection of a toxic element under low neutron and gamma doses. PMID- 4018898 TI - Synthesis of [18F]2-deoxy-2-fluoro-D-glucose from highly reactive [18F]tetraethylammonium fluoride prepared by hydrolysis of [18F]fluorotrimethylsilane. AB - 18F-Labeled fluorotrimethylsilane was prepared by nucleophilic substitution of chlorotrimethylsilane with reactor produced [18F]fluoride. Hydrolysis of fluorotrimethylsilane by aqueous tetraethylammonium hydroxide followed by removal of water with a mechanical pump gave a powerful source of no carrier added nucleophilic 18F. Reaction of this purified 18F preparation with 4,6-benzylidene 1-beta-O-methyl D-mannopyranoside-2.3-cyclic sulfate was complete in 2 min at 80 degrees C and gave two labeled products with similar retention times on reverse phase HPLC. Allowing for decay and handling losses during deprotection, the maximum yield of [18F]2-deoxy-2-fluoro-D-glucose from no-carrier added tetraethylammonium fluoride was 50%. Incorporation of 18F into organic products was 30% complete in 10 min at room temperature. An identical time-course was observed for reaction of 3-O-triflyl-1,2-5,6-diisopropylidene-D-allofuranose, the starting material for 3-deoxy-3-fluoro-D-glucose. Reaction of tetraethylammonium fluoride with chlorotrimethylsilane was more rapid and much more tolerant of water than the fluorosugar reactions. Chlorotrimethylsilane can be used to recover unreacted 18F from reaction mixtures. PMID- 4018899 TI - Synthesis and quality control of 99mTc-p-butyl IDA. AB - A procedure is described for synthesis of p-butyl IDA and for identification of the product by i.r. and NMR spectroscopy and by chemical analysis. A method for preparing this compound by "instant" technique and for its labelling with 99mTc is also given, as well as a procedure for control of the chemical and biological properties of the radiopharmaceutical. Radiochemical study shows a high labelling yield of 95%. Investigation of the biodistribution proves that this preparation is a good hepatobiliary reagent, suitable for use in investigation of the liver functions and for quantitative visualization of the hepatobiliary system. PMID- 4018900 TI - Tumor uptake of radiolabelled pyrimidine bases and pyrimidine nucleosides in animal models--VIII. Synthesis and tissue distribution of N-[2-(hydroxyethoxy) methyl]-5-[3H]methyluracil. AB - The tritium-labelled acyclonucleoside, N-[2-(hydroxyethoxy)methyl]-5 [3H]methyluracil (3H-3), was synthesized for evaluation as a tumor diagnostic agent. 5-[3H]-Methyluracil, 3H-1, was converted to the 2,4-bis-trimethylsilyl intermediate which was coupled with 2-acetoxyethoxymethyl bromide to afford 1-[(2 acetoxyethoxy)methyl-5-[3H]methyluracil (3H-2). Treatment of 3H-2 with sodium methoxide in methanol afforded 3H-3 (specific activity 188 MBq mmol-1. The tissue distribution of 3H-3 was examined in male BDF1 mice bearing Lewis Lung (LL) carcinomas. Long bone exhibited the highest tumor: tissue ratios. The kidney contained the highest radioactivity level relative to the tumor. This suggested a major urinary route of excretion. The major radioactive blood component (89.21%) was found to have a biological half-life of 0.19 min. The title compound is unsuitable for use as a diagnostic agent for LL carcinoma because of low tumor uptake and rapid urinary elimination of injected radioactivity from the body. PMID- 4018901 TI - A multivial distillation apparatus for routine tritium urinanalysis. PMID- 4018902 TI - 1-[11C]butanol: synthesis and development as a radiopharmaceutical for blood flow measurements. PMID- 4018903 TI - Structure confirmation and identification by predicted retention indexes in tritium labeling. PMID- 4018904 TI - The value of HLA phenotypes in the prognosis of Hodgkin's lymphoma. AB - The study included 52 patients with Hodgkin's disease, 32 males and 20 females, whose ages ranged from 3 to 36 years (34 under and 18 over 15 years). All patients were carefully staged, and lymph-node biopsies were taken for histopathological examination. HLA phenotype determinations were carried out, and the frequencies were statistically compared with those of normal Egyptian controls. We followed the patients for 3 years to monitor the effect of therapy. In order to determine the prognostic value of patients' characteristics (age, stage, histologic pattern and HLA phenotypes), statistical analysis and retrospective stratification studies were performed. The frequency of HLA-AI was significantly increased in our patients. The relative risk showed that persons carrying the AI antigen are 6 times more susceptible than those lacking it. There was no significant difference in the frequency of AI antigen in relation to the histopathologic subtypes. Furthermore, the results revealed a prognostic value of the HLA marker. In conclusion, we suggest that chemotherapy should be added to radiotherapy of marker-positive patients at any stage. PMID- 4018906 TI - Multipotentiality of yolk-sac carcinoma cell clones. AB - Yolk-sac carcinoma (YSCa) clones were isolated by manual cloning under visual control. By morphology, immunohistology and histochemistry the clones were shown to differentiate in vitro into visceral and parietal yolk-sac cells and in vivo into visceral and parietal yolk-sac cells, trophoblast and mesenchyme. Trophoblast and mesenchyme were only recorded in rat YSCa derived from displaced yolk sac but not in embryo-derived YSCA. Hence YSCa cells displaying a visceral and parietal yolk-sac pattern as well as the trophoblastic and the mesenchymal structures should have a common cell ancestor. PMID- 4018905 TI - Endemic African Kaposi's sarcoma is not associated with immunodeficiency. AB - Twenty-seven histologically confirmed Kaposi sarcoma (KS) patients resident in the Kivu Lake area of eastern Zaire were examined for immune competence. Only KS cases of the endemic African type have been observed in this high-incidence area. The median duration of the symptoms was 6 years and ranged from 1 to 38 years. Forty-one controls matched for age, sex and tribe and unrelated to the KS patients were selected from the community. Thirteen additional controls were first-degree relatives of the KS patients. No evidence of immune suppression among KS patients was found and there were no significant differences in the immune status between KS patients and controls. Total lymphocytes, B and T cells, and OKT4+ and OKT8+ cells varied within the normal range. Grouping of the KS patients in categories according to duration and disease extent did not reveal significant differences in their immune status. The number of KS patients reacting positively in a skin test to 5 recall antigens and I mitogen was similar to that of controls, except in the case of candidin, to which a higher number of KS patients were negative. The serum levels of immunoglobulins, complement factors and circulating immune complexes were comparable in KS patients and controls. Indicators of inflammatory processes [white blood cells (WBC), complement-reactive protein (CRP)] were positive in 27% of the KS patients. The prevalence and mean titer of antibody against cytomegalovirus (CMV), Epstein-Barr virus (EBV), hepatitis B virus (HBV) and syphilis were similar in KS patients and in controls. PMID- 4018907 TI - The interaction of melanoma cells with fibroblasts and endothelial cells in three dimensional macromolecular matrices: a model for tumour cell invasion. AB - Comparative quantitative data are presented concerning the adhesion, proliferation and invasive behaviour of RPMI-3460 melanoma cells on (1) plain collagen gels, (2) monolayer cultures of fibroblasts and endothelial cells growing on the gel surface, and (3) the exposed endothelial and fibroblast extracellular matrices (ECMs). Both types of ECMs enhanced melanoma cell adhesion and proliferation (compared with plain gels) and had marked, but distinctive, effects on melanoma morphology. The thickness and composition of the ECMs was altered by treatment of the matrices with enzymes (trypsin, elastase and chondroitinase ABC) or by using ECMs produced by endothelial cells at various times after confluence. Variations in the thickness and composition of the ECMs had no effect on the behaviour of melanoma cells growing on these matrices; our results suggest that the glycoproteins and glycosaminoglycan ECM constituents removed by digestion with the enzymes do not play an important role in melanoma cell attachment, proliferation and migration. Melanoma cells plated on the surface of a plain collagen gel rapidly migrated down into the collagen matrix, with approximately 30% of the cells found within the gel after 6 days of incubation. Fibroblast and endothelial ECMs significantly and distinctively inhibited melanoma invasion into the underlying collagen gel. The extensive invasion of melanoma cells into the gel was not accompanied by hydrolysis of the collagen fibres. Conversely, fibroblast and endothelial ECMs, which acted as effective barriers, were extensively hydrolysed by the melanoma cells. The possible use of ECMs deposited on collagen in the study of melanoma local invasion (on fibroblast ECMs) and extravasation (on endothelial ECMs) is discussed. PMID- 4018908 TI - Gastrointestinal carcinoma-associated antigen detected by a monoclonal antibody in dysplasia and adenocarcinoma associated with chronic ulcerative colitis. AB - Colorectal tissue specimens from 13 patients with chronic ulcerative colitis, of whom all had epithelial dysplasia and 2 had adenocarcinoma, were tested for the presence of gastrointestinal carcinoma-associated antigen (GICA), using an immunoperoxidase technique with a monoclonal antibody (MAb) against this antigen. GICA was present in the formaldehyde-fixed and paraffin-embedded sections of dysplastic and cancer tissue but absent from normal or hyperplastic epithelium. However, the pattern and extent of staining with the antibody did not correlate with the degree of dysplasia, i.e., "mild" dysplasia was often positive, and "severe" dysplasia was sometimes negative. Changes classified as "indefinite for dysplasia but probably negative" were variable in their expression of GICA. The adenocarcinomas were selectively labelled within cell clusters. In contrast, ulcerative colitis (UC) patients with severe inflammatory changes but with no detectable dysplasia were negative for GICA. GICA could be eluted from paraffin blocks of dysplastic tissue and biochemically characterized as a glycolipid. The detection of this antigen might be a useful complement to morphological examination in discriminating between precancerous and benign epithelial lesions of the colon. PMID- 4018909 TI - Tumor-derived chemotactic factor(s) from human ovarian carcinoma: evidence for a role in the regulation of macrophage content of neoplastic tissues. AB - Supernatants from freshly disaggregated human ovarian carcinomas maintained in vitro for 24 hr, from primary ovarian carcinoma cultures (4-6 days in culture) and from established ovarian cancer cell lines were examined for chemotactic activity on blood monocytes in blind-well chemotaxis chambers. Tumor-cell culture supernatants induced migration of peripheral blood monocytes across polycarbonate filters with considerable heterogeneity among different tumors. Induction of migration occurred only in the presence of a gradient between the lower and upper compartments of the chamber. Chemotactic activity was characterized by means of supernatants from primary ovarian carcinoma cultures. Chemotactic factor(s) was (were) produced in serum-free conditions and the production was inhibited by emetine but not by mitomycin C. The activity was destroyed by exposure to proteolytic enzymes and by heating at 100 degrees C but was unaffected by RNase, DNase, lipase and exposure to extreme pH values or heating at 56 degrees C. Upon fractionation on Sephadex G 75, the activity eluted as a single peak in the cytochrome C region, corresponding to an apparent molecular weight of about 12 kd. The percentage of macrophages was assessed in 25 freshly disaggregated tumor specimens. Ovarian carcinomas were heterogeneous in their macrophage content with values ranging from 4 to 36%. A significant (r = 0.62; p = 0.00097), though far from absolute, correlation was found between chemotactic activity of culture supernatants and percentage of tumor-associated macrophages. Tumor-derived chemotactic factor(s) could be one of the mechanisms involved in the regulation of the macrophage content of human ovarian carcinomas. PMID- 4018910 TI - Migration and death from malignant melanoma. AB - The age-standardized mortality rates for malignant melanoma of the skin in immigrants to New Zealand were compared with those of New Zealand-born non Maoris. Immigrants from European countries had mortality rates that were generally similar to those prevailing in their countries of origin, although, among immigrants from the British Isles, early age at migration was associated with a mortality rate similar to that of New Zealand-born non-Maoris. In a community survey, British immigrants were not less likely to have had severe sunburn, but had fewer moles, than New Zealand-born non-Maoris. The lower melanoma mortality, and the effect of age at migration, could be mediated by differences in mole frequency. PMID- 4018911 TI - Prevalence of polyps in an autopsy series from areas with varying incidence of large-bowel cancer. AB - The results of this multicentre autopsy study emphasize the relationship between the prevalence of adenomas and the incidence of large-bowel cancer. The highest proportion of autopsies with adenomas was observed in the area with the highest incidence of large-bowel cancer. The segmental distribution of adenomas within the colon was found to be similar to the site distribution of cancer. However, the lowest proportion of adenomas was found in the rectum, the segment in which cancer is most frequent. The latter finding suggests that either the adenoma carcinoma sequence is a less important pathway in the pathogenesis of rectal cancer, or that more rectal than colonic adenomas become malignant. The high proportion of hyperplastic polyps in the rectum, and statistically significant regional differences following the same patterns as the incidence of rectal cancer suggest that there could be at least an indirect relationship between hyperplastic polyps and cancer of the rectum. Adenomas of both colon and rectum were more frequent in men than in women, contrary to findings with colon cancer. However, as for colon cancer, the sex ratio of adenomas changed with age, from slightly below unity in persons under 65, to above unity for those aged 65 and over. A major difficulty that emerged was the histological identification of "polyps" because of the degree of autolysis of epithelial cells in the mucous membrane, and this difficulty largely contributed to the poor consistency of histological reporting. Regular consistency surveys of histological preparations should be recommended in any type of multicentre study in which histological examination is included. PMID- 4018912 TI - Proliferative abnormalities of the oesophageal epithelium of Chinese populations at high and low risk for oesophageal cancer. AB - Studies on the pattern of proliferation of epithelial cells from the oesophagus of 33 individuals from Linxian, a high-risk area for oesophageal cancer in China, and of 22 subjects from Jiaoxian, a low-risk area for the same cancer in China, were performed using thymidine labelling. Oesophageal biopsies were obtained during endoscopic surveys carried out in these 2 populations. A clear difference was observed between the 2 groups; the high-risk group showed cell proliferation in the upper layers of the epithelium more often than the low-risk group. No difference was found in the cell proliferation patterns of subjects with oesophagitis and those without oesophagitis in the high-risk area. This finding could suggest that the tritiated thymidine assay may be a more sensitive method to characterize the precancerous lesions of the oesophagus in high- and low-risk populations than simple histological evaluation. PMID- 4018913 TI - Differentiation of Abelson murine leukemia virus-infected promonocytic leukemia cells. AB - Virus-producing, tumorigenic, promonocytic leukemia cell lines were derived from Abelson murine leukemia virus-infected mice. This study shows that, of these 25 cloned lines, 22 were capable of extensive differentiation. It also shows that granulocyte-macrophage colony-stimulating activity increased the proportion of differentiating cells in 17/22 lines. Cells from agar colonies with a diffuse colony morphology had an increased expression of mature macrophage phenotypic characteristics, and a reduced proliferative capacity in vitro, compared to cells from agar colonies with a compact colony morphology. Cells from diffuse colonies also produced less Abelson virus, and were less tumorigenic in vivo than cells from compact colonies. Together, these results suggest some Abelson virus producing leukemic cells are not blocked in their capacity to differentiate and are capable of reversing the transformed phenotype. PMID- 4018914 TI - Interaction between two cellular subpopulations of a rat colonic carcinoma when inoculated to the syngeneic host. AB - From a single, chemically-induced rat colonic carcinoma, two subpopulations of tumor cells have been isolated. When injected into syngeneic rats, TR cells give rise to progressive tumors in most of the animals, whereas TS cells give rise to no tumors or to tumors which regress in less than 30 days. TS cells inhibit the growth of TR tumors, whether they are injected before TR cells or simultaneously, at a different site or mixed with the TR cells. Lymph nodes and spleen lymphocytes from animals having rejected TS tumors also inhibit TR-cell growth. On the other hand, TS cells are able to give rise to progressive tumors when they are injected into rats bearing established TR tumors. Lymph nodes and spleen cells of TR tumor-bearing rats are able to enhance TS cell growth. These results suggest that subpopulations of cancer cells contained in the same tumor interact with each other through their effect on the host immune system. The growth of a whole tumor probably depends not only on the growth potential of each constituent subpopulation, but also on the interaction between the subpopulations themselves. PMID- 4018915 TI - Thoughts on eponyms. PMID- 4018916 TI - Conduction tissue anomalies in absence of the right superior caval vein. AB - The incidence of electrical instability of the heart is high in patients with absence of the right and persistence of the left superior caval vein when the latter connects to the coronary sinus. It has been suggested that a large coronary sinus may influence the susceptibility to arrhythmias. we studied the conduction tissues of 8 hearts from the cardiopathological collection of Children's Hospital of Pittsburgh. Six of these specimens had a persistent left superior caval vein connecting to the coronary sinus. There were 4 with absence of the right superior caval vein, 3 of which were in the group with persistent left veins. We evaluated the sinus node and the specialized atrioventricular junctional area, comparing them with known normals. The coronary sinus varied in size from through it. The size did not alter the histology of the adjacent conduction tissue. In contrast, the sinus node was abnormal in 3 of the 4 hearts with absent right superior caval vein. This may be the key factor in the development of arrhythmias when the right superior caval vein is absent or abnormal. PMID- 4018917 TI - Abnormal heart rate control in vasospastic angina: effects of calcium antagonists. AB - We examined the effects of administration of calcium antagonists on the heart rate response to treadmill exercise in 11 patients with vasospastic angina and 8 healthy young volunteers. The exercise test was performed by walking on a treadmill at a constant speed and grade according to a scheme of pseudo randomized sequence for 19 min. The dynamic property of heart rate response to exercise was evaluated by using a frequency analytic procedure. The exercise test was also studied in 21 age-matched normal controls without drug administration. Administration of calcium antagonists revealed no significant effects on heart rate and blood pressure at rest in young healthy subjects or in patients with vasospastic angina. Young volunteers showed the same normal properties of heart rate response to exercise before and after calcium antagonists. Vasospastic angina showed abnormal heart rate response to exercise and revealed characteristically different transfer function from that in normal controls. These characteristics were not affected by treatment with calcium antagonists except for a slight, uniform decrease of gain of the system over the whole frequency range. Accordingly, the present exercise test can feasibly be used in the diagnosis and management of vasospastic angina even when calcium antagonists are administered to the patients. PMID- 4018918 TI - Congenital absence of the circumflex coronary artery associated with dilated cardiomyopathy. AB - We report the first autopsied case of congenital absence of the left circumflex coronary artery. The patient was a 12-year-old girl in whom the clinical diagnosis was idiopathic dilated cardiomyopathy. This type of heart disease is uncommon among children. The coexistence of the two conditions therefore suggests a possible aetiologic relationship between them. The pathological findings, however, do not support such an association. Rather, they suggest that they co exist by chance. PMID- 4018919 TI - Successful surgical repair of a patent arterial duct (ductus arteriosus) in a 63 year-old woman. PMID- 4018920 TI - Congenital aortic atresia with intact ventricular septum and normal left ventricle. Diagnosis by cross-sectional echocardiography. PMID- 4018921 TI - An eclectic hypno-emotive approach to psychotherapy. PMID- 4018922 TI - German norms for the Harvard Group Scale of Hypnotic Susceptibility, Form A. PMID- 4018923 TI - Estimates of hypnotizability: standard group scale versus subjective impression in clinical populations. PMID- 4018924 TI - Hypnotizability as a factor in the hypnotic treatment of obesity. PMID- 4018925 TI - Evaluation of a brief group treatment package including hypnotic induction for maintenance of smoking cessation: a brief communication. PMID- 4018926 TI - The localization of antibiotics by continuous sucrose gradient density. AB - Rat kidney was homogenized and centrifuged by continuous sucrose gradient density. Aminoglycosides and beta-lactam antibiotics were localized in the lysosomes, whereas the localization of tetracyclines was in the mitochondria. This study demonstrated a technique for the localization of antibiotics in the subcellular fractions without the use of a radioactive tracer. PMID- 4018927 TI - Reversibility of antibiotic incorporation in large organelles of kidney cell. AB - Large organelles, namely mitochondria and lysosomes, were fractionated from rat kidney. Antibiotics were added to the fraction and recombinated with no antibiotic-containing supernatant fraction. Tetracycline was quickly dissolved from the large organelle fraction. Cephaloridine had more affinity to organelles than tetracycline. Binding of amikacin was strongest and partly irreversible when added in vivo. PMID- 4018928 TI - Neurosecretory response of hypothalamic-hypophyseal axis to spinal anesthesia, minor gynecological surgery and irradiation. AB - The effect of spinal anesthesia, dilatation and curettage plus the first intracavitary radiotherapy or only that of intracavitary radiotherapy on growth hormone (HGH = the response of anterior pituitary) and arginine vasopressin (AVP = the response of posterior pituitary) levels was studied in 10 patients suffering from cervical or endometrial uterine cancer. Differing from earlier animal studies, irradiation had no effect on GH or AVP secretion, nor was there any change in the hormone levels following spinal anesthesia and dilatation and curettage. The neurosecretory response of hypothalamic-hypophyseal axis to spinal anesthesia and minor gynecological surgery appears to be minimal. PMID- 4018929 TI - Pharmacokinetics and absolute bioavailability of intramuscular tranexamic acid in man. AB - The bioavailability of tranexamic acid after the administration of a single intramuscular dose was estimated in three healthy male volunteers. 500 mg tranexamic acid were given intramuscularly and intravenously, as a bolus injection, to each subject on separate occasions. Following intramuscular administration, the peak plasma concentrations were attained after approximately one hour and the apparent elimination half-life was about two hours. The absolute bioavailability was 105.2 +/- 10.7% (mean +/- SD). At the dose given, the bioavailability of tranexamic acid after intramuscular administration is fast and complete. PMID- 4018930 TI - Chloroquine kinetics in normal and P. knowlesi infected rhesus monkeys. AB - A single oral dose of 20 mg/kg body weight of chloroquine was administered to normal and P. knowlesi infected Rhesus monkeys. The plasma chloroquine half-life was significantly increased (p less than 0.05) in infected monkeys as compared to the normal monkeys. The clearance and volume of distribution were significantly decreased in the infected monkeys. The decreased elimination half-life of the drug in infected monkeys could be due to hepatic involvement during malaria infection. PMID- 4018931 TI - A simple approach to estimate the variability of individual plasma drug concentrations in patients at a standardized multiple dosing regimen. AB - Equations were derived to simulate the course of plasma drug concentration versus time curves for a multiple dosing regimen of drugs with a long biological half life in those cases when Vrel and t1/2 or k in a particular subject do not correspond to the average values underlying the calculation of a standard dose. Extreme course can be expected only when Vrel and t1/2 show deviation from the average values in the opposite direction. Thus, smaller Vrel and longer t1/2 result in an increase, greater Vrel and shorter t1/2 in a decrease in plasma drug concentration after giving the standard dose. An analysis of the course of plasma drug concentration curves at the loading phase permits the estimation of the actual t1/2 in the particular subject. As an application example, the loading phase of digitoxin is presented. The procedure allows an individual dosage adjustment on the condition that plasma drug concentration in the particular subject can be monitored regularly. PMID- 4018932 TI - Hypercalcemia in 25 OH D3 treated patients receiving a calcium exchange resin. AB - Seven patients with advanced renal failure, six of whom were dialysed, received a cation exchange resin in the calcium cycle because of severe hyperkalemia, together with their usual preventive treatment of renal osteodystrophy, including 25 hydroxycholecalciferol. Hypercalcemia developed in four subjects within less than thirty days and disappeared within four days following the withdrawal of the resin. Patients who exhibited hypercalcemia had higher calcium intake, lower predialysis blood calcium and higher PTH values before introduction of the treatment. Three of the four hypercalcemic patients were diabetics. It is therefore advised to frequently monitor blood calcium when using calcium exchange resin in patients treated with vitamin D analogs. PMID- 4018933 TI - Influence of drug therapy on bronchial hyperreactivity. AB - Bronchial hyperreactivity was confirmed in eleven nonselected patients with chronic respiratory disease during a period of quiescence by inhalative provocation with histamine. After one week's treatment with ketotifen a protective effect against the histamine-induced bronchospasm was observed in nine patients. The rapid appearance of this protective mechanism was demonstrated both in patients with exogenous and endogenous bronchial asthma and in the three patients with chronic bronchitis. Regardless of the fact that specific bronchospasmolysis is the main therapeutic measure, based on our experience the protective mechanism of mast-cell stabilizers as supplementary therapy is at present at an earlier point of time than is generally assumed. PMID- 4018934 TI - Hospital staff's perceptions of the alcoholic. AB - Hospital staff's perceptions of the characteristics of alcoholics were investigated by means of a questionnaire containing a set of 23 semantic differential scales on which they rated four types of patient: "the Alcoholic," "the Nondrinker," "the Drug Addict," and "the Heavy Drinker." Factor analysis of the responses showed that types of patients were perceived in terms of three dimensions. Stability, Dangerousness, and Self-Assertiveness. In comparison with heavy drinkers, alcoholics were perceived by hospital staff in general as unstable, harmless, and self-effacing, though clerks tended to see them as more dangerous than did professionals. These perceptions are considered in relation to the respondent's own frequency of drinking. Finally, the explanation of these findings and their implications for clinical education and policy are discussed. PMID- 4018935 TI - A conceptual framework and treatment strategy for the alcoholic urge to drink utilizing hypnosis. AB - The present paper proposes a theoretical framework and a treatment strategy for dealing with the urges to drink that alcoholics experience during recovery. Two models are proposed: the Defense Model and the Conditioning Model. Each model covers a specific period of time during recovery in which the urges to drink occur. The Defense Model describes the urges that result in the initial recovery period, while the Conditioning Model is invoked to explain urges that materialize in the later phases of recovery. Next, a treatment strategy is delineated that incorporates these models and employs the use of hypnosis. The treatment strategy is divided into three phases, with the first and second phases dealing with the alcoholic's unconscious and the third phase being directed at the alcoholic's conscious. PMID- 4018936 TI - Ex-addict versus nonaddict counselors' knowledge of clients' drug use. AB - The accuracy of drug counselors' knowledge of their clients' drug use was assessed to determine whether counselor reports might constitute adequate research and evaluation data. Ex-addict paraprofessionals, non-ex-addict paraprofessionals, and degreed professional counselors (N = 82) reported on the drug use by 302 methadone maintenance and drug-free outpatient clients, as did the clients themselves. Counselor nonresponse rates to individual drug category items were acceptably low (less than or equal to 5%) for all but marijuana/hashish and over-the-counter drugs. Counselors' estimates of drug use rates at a group level were relatively accurate. However, reliability coefficients reflecting accuracy on a case-by-case basis were lower than desirable for use in prediction schemes for individual clients. Ex-addicts were overall somewhat more accurate than the other counselor groups. PMID- 4018937 TI - Issues of transference in methadone maintenance treatment. AB - Methadone maintenance treatment involves a great deal of governmental regulations and controls which have to be enforced by the clinician, thus having important transferential implications for therapy. This issue is explored on the basis of a case example, and recommendations are made to detach rule enforcement from therapy. PMID- 4018938 TI - Factors which differentiate cocaine users in treatment from nontreatment users. AB - This study compares a sample of cocaine users in drug treatment programs to a sample of cocaine users not in treatment. These samples were compared on: (1) level of cocaine use, (2) consequences of user, (3) employment, (4) social support system, and (5) criminal behavior. These attributes were related to being in treatment. Among intermediate-level cocaine users, friendship patterns, employment, and criminal history were associated with treatment status. The implications for the treatment of cocaine use are addressed. PMID- 4018939 TI - Attitudes toward smoking and smoking rate: implications for smoking discouragement. AB - Attitudes toward smoking were measured among nonsmokers and five levels of smokers (light to heavy). Of 13 attitude items, a relationship between attitudes and number of cigarettes smoked was found to exist in five, three of which dealt with smoking as a health risk. The results suggest that the more cigarettes a person smokes, the greater the likelihood of denial of the health hazards associated with smoking. PMID- 4018940 TI - Comparative admission and follow-up study of American Indians and whites in a youth chemical dependency unit on the North Central Plains. AB - In this study of drug-abusing young adults in North Dakota, we found that nonrural youth were more likely to be in a state treatment program than rural youth. We found few etiological differences between White and Indian Youth, although Indian youth were overrepresented tenfold. They could be described as young people in trouble at school and with the law, who were sexually involved but not religiously so. In a 6-month follow-up study, positive outcome data were much stronger for White than Indian patients, raising important questions about the effectiveness of such programs for the Indian patients. PMID- 4018941 TI - Clinical pharmacology of loop diuretics: a comparative study. AB - The authors performed two studies to clarify the characteristics, analogies and differences of three loop diuretics (furosemide, bumetanide and piretanide) aiming at more precise indications for their clinical use. In the first study, they compared bumetanide and piretanide by the method of compensated diuresis; in the second, they tested the three loop diuretics' efficacy in refractory ascites. The authors demonstrated that with the three substances analogous results were obtained when administered at equivalent doses and that only intensive diuresis was able to resolve refractory ascites. PMID- 4018942 TI - Adrenocortical function during prolonged treatment with clobetasone butyrate in children with chronic atopic dermatitis and elevated IgE levels. AB - Twelve children with chronic atopic dermatitis and elevated IgE levels (age range: 2-13 years; mean age = 8.2 +/- 3.5 years) were selected for the study and treated with clobetasone butyrate (0.05% cream) thrice daily during the first week, then twice daily for three weeks. Adrenocortical function was evaluated at the beginning and the end of treatment period. The results show that there was no statistically significant change in adrenal function during the study period (tetracosactrin test). The results of the immunological studies, namely total IgE using the paper disc radioimmunoassay technique, specific IgE using the radioallergosorbent test and immunoglobulin levels are given. PMID- 4018943 TI - Comparison between ranitidine and cimetidine in the short-term treatment of duodenal ulcer. AB - Two groups of 46 and 49 patients each with endoscopically proved duodenal ulcer and not previously treated, received ranitidine (150 mg X 2 daily) and cimetidine (1 g/day) respectively for eight weeks. The disappearance of the ulcer was observed endoscopically in 78% of both the first and second groups of patients. Of the ten patients non-responders to ranitidine, six were treated again for eight weeks with ranitidine and four with cimetidine for eight weeks; all of them recovered completely apart from one of the cimetidine treated patients. Of the 11 patients non-responders to cimetidine, seven were retreated with cimetidine and 4 with ranitidine for a further eight weeks and all of them obtained a complete recovery except for one of the cimetidine treated patients. No relevant side effects were observed with either drug. In conclusion cimetidine and ranitidine showed a comparable therapeutic value. PMID- 4018944 TI - Epidemiological basis for chemotherapy of human echinococcosis. AB - Cystic (E. granulosus) echinococcosis is an important medical problem in Mediterranean countries where the dog-sheep-dog strain predominates. This mainly man-made infection is susceptible to control programmes directed against the infections in dogs. In man, surgery still remains a major curative intervention. Some benzimidazole compounds (mebendazole, albendazole) are effective in some cases of cystic echinococcosis, however, further studies on more effective drugs are recommended. At present chemotherapy should be used only in inoperable cases of cystic echinococcosis in man. Alveolar (E. multilocularis) echinococcosis is diagnosed more and more frequently in some regions of Central Europe. Man cannot interfere much with the reservoir of E. multilocularis in wild life, but should be able to protect himself and his dogs against infection from natural foci. High doses of mebendazole taken continuously have shown to increase substantially the survival rate of infected patients. However, further studies are needed to improve the efficacy of chemotherapy and to make it available to all those patients who have not been cured by surgery. PMID- 4018945 TI - Pharmacokinetics of dibekacin in children with cystic fibrosis. AB - Dosages and pharmacokinetics of dibekacin were studied in a group of 15 children with cystic fibrosis (CF) and a control group of 9 children. The mean dosage regimens of dibekacin were respectively equal to 2.19 mg/kg and 2.16 mg/kg in the CF and non-CF patients. The mean peak serum values for the CF and non-CF groups were respectively equal to 5.3 micrograms/ml. Comparison of pharmacokinetic parameters (i.e. half-life, distribution volume, total body clearance and area under the curve) showed no significant difference between the two groups (p greater than 0.05). PMID- 4018946 TI - Long-term intermittent netilmicin therapy of chronic pyelonephritis: a pharmacokinetic and clinical study. AB - A trial was conducted with long-term intermittent netilmicin therapy in six patients suffering from chronic pyelonephritis. Netilmicin was given in full dose for a period of 3-10 days (2-6 mg/kg/day), followed by 2 mg/kg doses once or twice weekly for 3-6 months. Individual doses were determined by computer based on the age, sex, lean body weight and serum creatinine concentrations of the patients. During the full-dose period of treatment netilmicin concentrations in serum were between 2 and 16 mg/l in serum and between 50 and 200 mg/l in urine. During intermittent treatment serum levels remained below 2 mg/l (except for 8-12 hours after dosing); in the urine concentrations were permanently in therapeutic ranges (150-4 mg/l). Renal tissue levels were simulated. Six to 12 months after long-term netilmicin treatment all patients are abacteriuric and free from symptoms. No auditory or renal toxic effects occurred. PMID- 4018947 TI - Plasma levels and urinary excretion of verapamil, norverapamil, N dealkylverapamil (D617), N-dealkylnorverapamil (D620) following oral administration of a slow-release preparation. AB - The kinetics of verapamil and of its N-dealkylated metabolites (norverapamil, D617, D620) were studied in six cardiac patients with normal cardiac indexes after 120 mg oral administration of the drug both as conventional preparation and as slow-release preparation. Following a dose of the slow-release preparation, the drug concentration curves were smoother and the mean bioavailability was lower in comparison with the conventional preparation. A patient taking inducing agents (phenobarbital and phenytoin) exhibited a strikingly low bioavailability. Following administration of the conventional preparation, the mean plasma half lives of verapamil, norverapamil, D617 and D620 were 4.4, 6.6, 8.5, and 15.8 h respectively and the drug concentrations showed a triexponential decay. Urinary excretion data indicate that a saturation phenomenon may occur at level of renal tubular transport and that a competition may be suspected between D620 and the other compounds. It is concluded that various mechanisms, i.e. changes in hepatic and renal clearances, occurrence of a deep compartment, and the properties of the pharmaceutical preparation may affect verapamil kinetics during long-term treatment. PMID- 4018948 TI - Neuromuscular disorders associated with D-penicillamine treatment for rheumatoid arthritis. AB - Three cases of D-penicillamine (DPA) induced myasthenia gravis (MG) and one case of DPA-induced polymyositis (PM) are reported among four patients suffering from seropositive rheumatoid arthritis. The cumulative doses responsible for the three DPA-induced MG cases amounted respectively to 73, 117 and 467 g. The cumulative dose responsible for the DPA-induced PM case amounted to 465 g. All the patients were HLA DR1. All four cases healed completely after withdrawal of DPA. The aetiology of the cases is discussed and the literature is reviewed. These cases represent further instances of DPA-induced neuromuscular disorders. PMID- 4018949 TI - Absorption and disposition kinetics of flunoxaprofen and benoxaprofen in healthy volunteers. AB - Flunoxaprofen is a new nonsteroidal antiinflammatory agent that, like benoxaprofen, inhibits leukotriene rather than prostaglandin synthesis. The absorption and disposition kinetics of flunoxaprofen and benoxaprofen have been compared in six healthy volunteers after oral administration of 100 mg of each drug. The two drugs showed similar absorption characteristics, whereas the distribution and elimination processes were much faster for flunoxaprofen. The renal route of elimination appeared to contribute significantly less to the disposition of flunoxaprofen. These kinetic characteristics render less likely the risk of excessive drug accumulation with flunoxaprofen, especially in the presence of reduced renal function. PMID- 4018950 TI - Pharmacokinetic aspects of cerebrospinal fluid penetration of fosfomycin. AB - Even today antibiotic therapy of postoperative or posttraumatic meningitis remains a problem. In patients in a neurosurgical intensive care unit, nosocomial microorganisms with high resistance are mainly found. There are no antibiotics available which have simultaneously a good efficacy on the higher resistant nosocomial microorganisms and a good penetration through the blood-brain or blood cerebrospinal fluid barrier. We analysed the cerebrospinal fluid (CSF) penetration of fosfomycin carrying out the investigations in patients in whom a CSF drainage was required for a neurosurgical indication. The blood-brain barrier was considered to be largely intact (total CSF protein and cell counts with in the normal range). Five or 10 g fosfomycin were administered to adults in 30 min infusions. After administration of 5 g, the CSF concentration formed a plateau between 8.6 and 9.9 micrograms/ml 3 to 6 h after the infusion. Increasing the dose infused (10 g) markedly shortened the latency period between reaching a sufficient concentration of fosfomycin in the CSF. With repeated doses of fosfomycin (3 X 5 g/day) the concentration in the CSF did not fall below the therapeutic level. Even in the presence of an intact blood-brain barrier, fosfomycin in our investigation showed a satisfactory penetration into the CSF. This is attributable to the favourable physicochemical state of fosfomycin (relative molecular mass 182). PMID- 4018951 TI - Clinical study on the efficacy of clofoctol in the treatment of infectious respiratory diseases. AB - The effectiveness and the safety of a new chemotherapeutic phenol derivative, clofoctol, was evaluated in adult hospitalized patients affected by infectious diseases of the bronchopulmonary tract. The clinical diagnosis included acute exacerbation of chronic bronchitis, acute bronchitis, bronchiectasis, pneumonia, bronchopneumonia and lung cavitary neoplasm. Expectoration, cough, dyspnoea, respiratory murmur and body temperature were considered as clinical factors to which an arbitrary score was given. Functional respiratory parameters including FVC, FEV1 and FEV1/FVC X 100 were also evaluated. All the patients were treated rectally with clofoctol 1500 mg daily for five days. Bacterial evidence of infection was obtained by sputum culture, which was repeated at the end of treatment. At that time, bacteriological results were 72.4% disappearance of baseline pathogens, 20.7% persistence of baseline pathogens and 6.9% presence of different organisms. Functional respiratory parameters were found to be significantly improved by treatment. Clinical results, arbitrarily evaluated on the basis of the overall assessment of laboratory and functional data, were excellent in 33.3%, good in 44.4%, fair in 5.6% and poor in 16.7% of patients. Tolerance was generally good; side-effects included maculopapular rash in 2 patients and rectal disturbances in 10 patients. In conclusion, for the treatment of bronchopulmonary diseases clofoctol offers an interesting alternative to antibiotic therapy. PMID- 4018952 TI - Chemoprophylaxis of postoperative infections in colorectal surgery. AB - Colorectal surgery involves a high risk of postoperative infections. The major risk factors can be reduced by appropriate preparation of the patient for the operation. Mechanical removal of gross faecal material from the bowel, possible before most elective operations, does not sufficiently reduce the incidence of postoperative infections. Prophylactic medication has not yet been widely accepted, although its effectiveness has been confirmed by a number of studies. Preoperative management of patients subjected to colorectal surgery at our institution in the last three years, consisted of mechanical cleansing of the intestinal tract for two days, followed by rapid intravenous administration of gentamicin 80 mg and metronidazole 500 mg in a single dose, 30 min to 1 h before the operation. From 1971 to 1973, the postoperative infection rate in 432 patients submitted to elective colorectal surgery was 29%. During the period 1981 1983, operations of the same kind were performed in 572 patients, the infection rate being 15%. Prophylactic single-dose administration of gentamicin in combination with metronidazole has proved to be very effective in reducing postoperative infections. PMID- 4018953 TI - Review of the experience with cefotaxime in surgical prophylaxis. AB - Besides being of benefit to the individual patient protected from complications in a variety of surgical procedures, antibiotic prophylaxis is cost effective and so also benefits the community. Whereas some authors recommend that third generation cephalosporins should not be used for prophylaxis, but be reserved for treatment of serious infections, others are of the opinion that the higher activity and broader spectrum of these antibiotics would protect more patients more effectively from postoperative infections, especially when the surgical procedure is indicated for prophylaxis and the antibiotic chosen is well tolerated. According to the references screened, surgical procedures are classified into three groups where: third generation cephalosporins should not be used, they are as equally effective as conventional agents, they--like cefotaxime -convey definitely additional benefit. PMID- 4018954 TI - Topical nitrogen mustard in mycosis fungoides. AB - A twelve-year experience in thirty-three patients suffering from early mycosis fungoides in the plaque stage confirmed the effectiveness of topical nitrogen mustard (chlormethine) therapy. Fourteen patients were in complete remission at the latest time of observation and seven in partial remission. The probability of freedom from relapse was approximately 50% after 6 and 12 years. Three deaths attributable to mycosis fungoides were recorded. Another three patients had to discontinue treatment due to contact dermatitis to nitrogen mustard. Specific precautions were undertaken in order to protect personnel handling the drug. No damaging or toxic effects were observed among staff and no haematological side effects were observed among the patients. The treatment as a whole was well tolerated. PMID- 4018955 TI - Treatment of dyslipidaemia with a simple low fat diet and with a combination of a low fat diet and a formulation containing soybean protein. AB - The first approach to treatment of dyslipidaemia is with diet. Currently, modified soybean protein is often included in the diet. A study was made of 32 patients with types IIa and IIb dyslipidaemia to see what changes in blood lipids could be induced by a simple low fat diet and a diet with modified soybean protein substituted for part of the animal protein. After six weeks on the initial low fat diet, all of the patients had lower total cholesterol and triglyceride levels, but there were no significant changes in the high density lipoprotein-cholesterol levels. The same diet was continued for eight weeks by 19 of the patients, who continued to improve. The 13 patients who had shown the least response to the initial simple low protein diet were given a diet in which the animal protein was partially replaced with modified soybean protein. This diet further decreased the total cholesterol. PMID- 4018956 TI - Slow-release lithium in treatment of schizoaffective syndromes. AB - Schizoaffective disorders are a blurred category of psychiatric pathology in which lithium seems to exert therapeutic effects. The present study was made on patients suffering from affective syndromes with positive schizophrenic symptoms ranging from none to severe. They were hospitalized because of an acute episode, treated with a slow-release lithium preparation (Hypnorex) following the attack therapy and followed up for a mean period of two years. Diagnosis were done according to the American Psychiatric Association diagnostic and statistical manual of mental disorders (DSM III) criteria, while clinical evaluations were carried out on the basis of an original lithium therapy assessment protocol. Lithium was demonstrated to be prophylactic to relapses of affective symptoms, its effectiveness as a whole being proportional to the purity of the major affective disorder. Slow release lithium was found a reliable pharmaceutical tool in both providing therapeutic results and avoiding severe side-effects. The therapeutic range of lithium serum levels was within 0.5-0.6 mEq/l. It is hypothesized that the response to lithium therapy could be a guide in the differential diagnosis between schizoaffective and schizoaffective-like syndromes. PMID- 4018957 TI - The natural history of jumper's knee. Patellar or quadriceps tendonitis. AB - We have reviewed the clinical records and the results of conservative and surgical treatment of 125 out of 172 cases of Jumper's Knee followed for at least 2 years since the onset of symptoms. All were athletes involved in various sporting activities. At follow up 15 patients had given up sport and the lesion had healed spontaneously. We used the classification of Blazina et al as modified by Roels et al. Twenty-four patients were in stage 1, 42 in stage 2, 43 in stage 3 and one in stage 4. Conservative treatment was used primarily on all patients with one exception where the tendon had ruptured. The results were very good in 42, good in 32, and poor in 43, but in 36 patients a long period of rest and reduction in sporting activity was necessary before a significant improvement was obtained. Operation was carried out on 16 patients (19 knees), 18 were in stage 3 and one in stage 4. Various surgical techniques were used. The results were very good in 7 knees, good in 5 and poor in 7. Operation is indicated after the failure of conservative measures and in patients who do not want to reduce their sporting level. The aim should be to induce healing at the bone tendon junction. We emphasize the importance of the prevention of jumper's knee in athletes. PMID- 4018958 TI - Fractures of the cervical spine in ankylosing spondylitis. AB - In the years 1965-1982, 33 patients with traumatic cervical spine injury in ankylosing spondylitis were treated in the Spinal Department of the Rehabilitation Clinic at Konstancin, Poland. This paper describes the causes of vertebral injury, the level and degree of spinal cord damage and the method and results of treatment. Injury of the ankylosed spine is often a consequence of minor trauma, such as a stumble in the street, but the damage to the spinal cord is often complete or extensive. Complete injuries of the spinal cord with subsequent disturbance of the autonomic system are likely to lead to the development of respiratory disorders, aggravated by the pathological changes associated with ankylosing spondylitis when the chest is fixed in the exhaling position. This may often lead to death. PMID- 4018959 TI - A new type of intramedullary nail for the internal fixation of subtrochanteric fractures of the femur. AB - The Author has developed a modified intramedullary nail for the stabilisation of fractures in the subtrochanteric and proximal one-third of the femur. Due to its three tapered fins the rod fits well into the funnel-like medullary cavity of the proximal femur preventing varus or rotational displacement of the proximal fragment. This method has been applied in 16 cases. Its particular advantages are the chance to perform the operation closed, a short operating time and period in hospital, early weight bearing and a simple surgical technique without the need for special instrumentation, requiring little radiographic exposure during surgery. The ideal and relative indications for the application of the technique are discussed. Biomechanical tests have confirmed that the finned medullary nail is the most stable method of fixation of the fractures when compared with other alternative devices. PMID- 4018960 TI - [Lamellar rotation osteotomy of the tibia in children]. AB - The authors describe the technique and results obtained by a derotation osteotomy of the tibia in children. The method is simple, reliable and does not require internal fixation. It is suitable for dealing with deformity following poliomyelitis, and may also be used to treat tibial torsion which fails to correct with growth in children who are otherwise healthy. PMID- 4018961 TI - The Larsen syndrome occurring in four generations of one family. AB - Details of eight (possibly nine) patients with autosomal dominant inheritance of the Larsen Syndrome are reported. They are from four generations of one family and particular reference is made to their complex foot deformities. PMID- 4018962 TI - Aneurysmal bone cysts of the spine. AB - Aneurysmal bone cysts of the spine are uncommon. In the English language literature, there have been less than one hundred reported cases. We present five examples, all of which arose in a vertebral body. One case is the first reported arising from the coccyx; one presented at the sixth thoracic vertebral body with complete paraplegia and two with extremely large abdominal masses and catastrophic bleeding during attempted open biopsy. All were resected by a one stage anterior or combined anterior-posterior approach. Two cases were treated with preoperative irradiation because of profuse, life-threatening bleeding during biopsy, and 4 weeks later complete anterior excision was carried out without difficulty. PMID- 4018963 TI - Curettage of benign lesions of bone. Factors related to recurrence. AB - In a retrospective study of 155 patients with different types of benign lesions of bone, the rate of recurrence following simple curettage was analysed in relation to sex, age, histological type, the location and the size of the tumour, and the type of bone graft used at operation. All patients were followed for a minimum of 2 years, 131 (85%) for 5 years and 101 (65%) for 10 years or more. The overall rate of recurrence was 23%. All recurrences except one were within 6 years of the initial operation, 80% within 3 years and 49% within 1 year. The overall rate of cure using curettage as the sole treatment, although repeated several times in some cases, was 95%. Only 5% of the patients required more extensive surgery, such as local resection (6 cases) and amputation (1 case), to control the tumour. The histological type and the sex of the patient proved to be the only factors statistically related to recurrence, although with solitary cysts the age of the patient was also relevant. Significantly higher recurrence occurred with giant cell tumours and aneurysmal bone cysts, in females, and with solitary cysts in patients under 9 years of age. This study of histologically different benign lesions treated in a uniform manner at a single centre shows that the rate of recurrence is strongly related to the type of tumour. The choice of treatment in patients with benign lesions of bone should be dictated by the histological appearance of the lesion. More extensive surgical procedures may not be necessary but other measures may be used in addition to curettage. PMID- 4018964 TI - Vertebral osteoid osteoma. A case report. AB - The early diagnosis of vertebral osteoid osteoma is frequently delayed due to the absence of radiographic changes. A bone scan is more helpful because it shows an increased uptake of isotope when plain radiographs still appear normal. The use of computed tomography will confirm the diagnosis, allow precise delineation of the lesion and enable planning of the correct operation. PMID- 4018965 TI - Complications with antibiotics used prophylactically in joint replacement surgery: a case report of cephradine-induced pseudomembranous colitis. AB - A woman underwent joint replacement surgery with prophylactic antibiotic cover, and subsequently died as a result of pseudomembranous colitis. We have noted a high incidence of antibiotic diarrhoea with cephradine, and suggest that if administration of prophylactic antibiotics is restricted to 3 days or less, the incidence of diarrhoea would diminish, and the therapeutic value of the antibiotics would be maintained. PMID- 4018966 TI - Posterior intertransverse fusion assessed clinically and with biplanar radiography. AB - Biplanar radiography was used to assess bony union after intertransverse fusion. The patients were assessed clinically and the fusion status was compared with the clinical result. Posterolateral intertransverse fusion was shown to be capable of fusing the motion segment almost completely. However, the strictly measured fusion rate was only 27%, but this increased to 91% when partial fusions were included. The fusion rate from conventional plain films assessed by the radiologist was 82%, which is similar to other reports. On clinical examination, a satisfactory result was obtained in 82%, but there was no clear correlation with fusion status. PMID- 4018967 TI - Soft disc herniation of the cervical spine. AB - The definition of soft disc hernia of the cervical spine is not always clear, so we have studied 34 cases where soft disc material was extruded or had migrated outside the intervertebral space. There were 22 cases of the paracentral-central type and 12 cases of the posterolateral type. The diagnosis was made by discography using anteroposterior, lateral and both oblique radiographs. All the patients complained of pain or discomfort in the neck or the interscapular region which was increased by the neck compression test and reproduced during discography. Severe pain in the area was present in all the cases of the posterolateral type and in about half of the paracentral-central type. Cord signs, such as increased reflexes in the lower limbs, were found in 15 cases of the paracentral-central type and in 5 cases of the posterolateral type. These signs correlated with the width of the spinal canal and the amount of prolapsed disc material. Discography and reproduction of pain were most useful for the diagnosis of this type of hernia. It has now become possible to differentiate the paracentral type from the central type by performing computerised tomography scanning after discography. We treated 12 cases conservatively and 22 cases surgically, and obtained good results in both groups. PMID- 4018968 TI - The treatment of brachial plexus injuries. AB - The author describes 1068 patients with brachial plexus lesions who were referred to him during a period of 18 years. Seventy two percent of the injuries were caused by road traffic accidents. Traction or crush injuries were the usual type encountered. They may occur at five levels above, behind and below the clavicle. Of 329 patients who underwent operation, 23% had an associated injury of a major vessel and 80% had multiple injuries elsewhere. The operative approach preferred is described and the principles governing the choice of nerve repair, nerve graft and nerve transfer are discussed. The details of the problems encountered and the procedures carried out in this group of patients are given, and the results obtained are closely analysed. In about 15% of supraclavicular injuries reconstruction of the plexus is worthwhile. The results in infraclavicular lesions are much better with a high level of success if treated early. Only 5 patients had direct lacerations of nerves of the plexus and another 5 had suffered gunshot wounds. Only 11 out of 80 cases of obstetric palsy seen since 1976 have been operated on. The majority of the patients were seen late. At operation similar lesions were encountered as in adults, and useful improvement was obtained in some cases. In post-irradiation lesions of the plexus good results may be obtained if operation is undertaken early. Otherwise surgery should only be performed to relieve severe pain. PMID- 4018969 TI - Posterior dislocation of the shoulder with a large anteromedial defect of the head of the humerus. A case report. AB - A new surgical technique for treating a posterior dislocation of the shoulder with a large anteromedial defect of the humeral head is described; it can be applied to those very severe dislocations that might otherwise be considered to need replacement or arthrodesis. A transverse osteotomy below the surgical neck of the humerus with lateral rotation of the head into anteversion limits medial rotation and this prevents the edge of the defect impinging on the posterior edge of the glenoid to cause redislocation. PMID- 4018970 TI - De Quervain's disease. An ultrastructural study. AB - The tendon sheaths of extensor pollicis brevis (EPB) and abductor pollicis longus (APL), obtained from four patients with de Quervain's disease were studied by light and electron microscopy. Three different layers were identified in the sheath which was much thicker than normal. Both the outer and the middle layers had thick bundles of collagen fibres with scattered fibroblasts. The inner layer was mainly formed by chondroid and myxomatous tissue. Collagen fibrils were thicker than normal, reaching 2100 nm in diameter. Numerous cells which resembled "myofibroblasts" were scattered throughout the whole thickness of the sheath. The results seem to indicate that thickening and hardening of the EPB and APL tendon sheaths in de Quervain's disease is caused by increased synthesis of the extracellular matrix, increased thickness of the collagen fibrils and areas of myxomatous and chondroid metaplasia. PMID- 4018971 TI - Aneurysmal bone cyst of the ischium. AB - The treatment of a patient with an aneurysmal bone cyst involving the pelvis by selective arterial embolism is described. After one year pain relief is complete and radiologically the lesion is healing with increased density of the cyst wall and intracystic trabecular bone formation. PMID- 4018972 TI - Liposarcoma: a ten year experience. AB - A retrospective study of all patients presenting with liposarcoma at Southend General Hospital between the years 1970 and 1979 is presented. There were 13 patients in the group treated with various combinations of surgery and radiotherapy. The histology has been reviewed: 7 patients had myxoid tumours, 2 well differentiated and 4 pleomorphic. The patients were followed up for between 18-109 months with 7 patients followed for more than 5 years. Local recurrence was seen only in myxoid tumours whereas pleomorphic tumours showed a high incidence of distant metastases. The length of survival was found to correlate with the histology, pleomorphic tumours being associated with the shortest survival. The series illustrates that the histological type of liposarcoma predicts the pattern of behaviour of the tumour and is the major determinant in prognosis. PMID- 4018973 TI - Patellofemoral function in total condylar knee arthroplasty. AB - A series of 100 total condylar knee arthroplasties was studied to determine radiographic and clinical patellofemoral function. Before operation there was lateral patellar tilt in 31 cases and lateral displacement in 52. After operation tilt was present in 8 and displacement in 14. Only a few patients had medial patellar displacement. Dislocation or fracture of the patella was not encountered. Six patients had postoperative patellar pain. In one case there was a radiolucent zone at the bone-cement interface in the patella, without pain. Patellofemoral function before operation was good in 3, fair in 54, and poor in 43 cases. After operation it was good in 88 and fair in 12. Both tilt and displacement slightly reduced postoperative patellofemoral function. Patellar reconstruction with the total condylar prosthesis shows reasonably good tolerance of moderate malpositioning of the patellar prosthesis, affords sufficient stability and usually painless patellofemoral function. PMID- 4018974 TI - Osteochondral hemiarthroplasty. An experimental investigation in baboons. AB - Hemiarthroplasty using osteochondral autografts and allografts were performed on 40 hip, 23 knee and 5 shoulder joints in baboons. Follow-up at one, two and three years revealed good results as assessed by clinical and radiological examination. Histological and radionuclide studies revealed cartilage viability in 70 to 80% of cases. PMID- 4018975 TI - Abstracts of the Third International Conference on Immunopharmacology. Florence, Italy, 6-9 May 1985. PMID- 4018976 TI - Alcohol and the skin. PMID- 4018977 TI - Clubbing of the fingers. PMID- 4018978 TI - Is there a South American pemphigus? PMID- 4018979 TI - Chromomycosis in Zaire. AB - Biopsy specimens from 17 Zairians with chromomycosis are described. Patients ranged in age from 20 to 50 years, with a mean of 37.2 (+/- 10.2). Chromomycosis was suspected clinically in only 3 of the 17 patients. In 14 patients the lesions were on the lower limbs and in 3 on the arms. The lesions were chronic, in one patient persisting for 9 years. The diagnosis was established in each patient by finding typical thick-walled brown fungi within the lesions. Some fungi were in abscesses, others were in histiocytes or giant cells. The fungi and the inflammatory reaction were concentrated in the upper dermis. Acanthosis, hyperkeratosis, and parakeratosis were constant features and pseudoepitheliomatous hyperplasia (PEH) was a feature in 10 patients. Transepithelial elimination (TEE) of fungi was a conspicuous feature in eight specimens. Microscopic features suggested TEE in an additional three. PEH and TEE were associated in all specimens. In patients with TEE, the diagnosis may be confirmed quickly by smearing surface scrapings and finding the characteristic brown fungi. PMID- 4018980 TI - Epidemiologic approach to community dermatology. AB - A survey on communicable dermatoses in economically weak villages in India showed wide variations in prevalence rates in similar ecologic setup. A skin diseases, on-spot-treatment, 1-day-camp was organized to treat 1787 subjects in five villages. Two applications of 1% lindane 1 week apart was the only treatment used without attending to hygiene for scabies and pediculosis. Application of 1% gentian violet with four daily doses of sulfamethoxy-pysidazine was administered for pyoderma. The cure rate for scabies and pediculosis was 86%. Epidemiologic determinants of communicable dermatoses are the most important factors in the practice of community dermatology. PMID- 4018981 TI - Concurrent development of pemphigus foliaceus and psoriasis. PMID- 4018982 TI - Pure neural leprosy diagnosed in the United States. PMID- 4018983 TI - Familial keratotic papular lesions on the chin. PMID- 4018984 TI - A marsupialization procedure for repair of large cutaneous surgical wounds. AB - An open method of surgical management of large postoperative surgical excision defects of the head and neck is a pragmatic alternative to more conventional methods of management. PMID- 4018985 TI - Epidermolysis bullosa. Assessment of a treatment regimen. AB - Nineteen patients with a variety of types of epidermolysis bullosa were initially assessed in an open study of a treatment regime for the genetic type of epidermolysis bullosa. Nine of the ten patients admitted to the hospital for treatment showed definite objective improvement with decreased number of blisters and increased rate of healing of blisters. The mean percentage decrease in blister numbers from the time of admission until discharge from hospital was 76%. Sixteen patients were followed as outpatients for 5-11 months. Two patients continued to show objective improvement, while eight reported more rapid healing of their blisters. Six patients failed to improve. This treatment has a beneficial effect in inpatients with epidermolysis bullosa. The improvement may be due to the intense topical treatment rather than to a specific item of the therapy. In the long term, this treatment has little effect on the formation of new blisters, but an accelerated healing of blisters is reported by 50% of the patients. PMID- 4018986 TI - The challenge of rural dermatologic care in developing countries. PMID- 4018987 TI - Indoor air pollution and its effect on pulmonary function of adult non-smoking women: I. Exposure estimates for nitrogen dioxide and passive smoking. AB - The potential effects of indoor NO2 and tobacco smoke on the respiratory system were studied using pulmonary function data from a longitudinal study. In 1982, NO2 was measured in 163 homes of non-smoking adult women and detailed information on smoking inside the house was gathered over the period 1965-1982. Personal exposure to NO2 was calculated from the measured levels and the activity pattern of the study population (range 11-139 micrograms NO2/m3). Historical exposure was estimated using regression models of NO2 on house characteristics. It is shown that estimation of historical exposure to indoor NO2 on the basis of house characteristics only is, at present, too inaccurate for use in epidemiological studies. Actual measurement of NO2 is unavoidable for exposure assessment in health effect studies of indoor exposure to NO2. PMID- 4018988 TI - Indoor air pollution and its effect on pulmonary function of adult non-smoking women: II. Associations between nitrogen dioxide and pulmonary function. AB - The association between nitrogen dioxide levels in homes and pulmonary function of 97 non-smoking adult women was investigated in a rural area in the Netherlands. The study population was a sub-sample of a longitudinal field study on chronic non-specific lung diseases which was started in 1965. Pulmonary function tests were performed at three-yearly intervals. NO2 was measured for one week in the winter in kitchen, living room and bedroom of each home. Cross sectional analyses showed negative associations between NO2 exposure and several pulmonary function parameters as measured in the 1982 study. No significant association could be found between NO2 exposure and pulmonary function decline since the start of the study. PMID- 4018989 TI - Indoor air pollution and its effect on pulmonary function of adult non-smoking women: III. Passive smoking and pulmonary function. AB - The association between pulmonary function and exposure to tobacco smoke in the home was investigated in a sample of adult, non-smoking women living in a rural area. The women were all participants in a large longitudinal survey on the natural history and determinants of chronic non-specific lung disease. On cross sectional analysis, several pulmonary function parameters were found to be significantly associated with exposure to tobacco smoke in the home. There was no association between exposure and pulmonary function decline. PMID- 4018990 TI - Hypertension and sources of blood pressure variability among Mexican-Americans in Starr County, Texas. AB - Previous investigations have established that the Mexican-American community of south Texas has a three- to five-fold elevated risk for non-insulin dependent diabetes mellitus when compared to the US population as a whole. In addition, evidence points to similarly increased risks of the related disorders, hypertension and obesity. In this paper, age- and sex-specific rates of borderline and definite hypertension among 1931 Mexican-Americans aged 15 years and above based on a single, at-home blood pressure determination are reported. Observed rates of definite hypertension are uniformly lower than the US population while borderline hypertension is correspondingly higher for all age and sex strata yielding overall prevalences of hypertension which are not significantly different. The Starr sample, however, has one and one-third times as many individuals taking hypertensive medications so that the true rate of hypertension is likely to be higher. Examining sources of blood pressure variability using analyses of covariance indicate that age has the most significant effect. A direct measure of body size was not available, but classification based on simple silhouettes representing body form is shown to be the next most significant effect. Furthermore, the silhouettes appear to provide nearly an equivalent amount of information as does the body mass index as an empirical predictor of blood pressure variability. Diabetic classification is a significant effect for systolic blood pressure in females, but not for males or for diastolic pressure in either. PMID- 4018991 TI - Cholesterol intake as measured by unquantified and quantified food frequency interviews: implications for epidemiological research. AB - A number of dietary assessment methods have been developed for epidemiological investigations. The general tendency has been to strive for methods that are sufficiently simple to implement in a fairly large sample of respondents and yet are able to measure dietary intakes with an acceptable degree of reliability. Concomitantly, methodological studies are needed to determine whether the various methods can be used interchangeably. This study compares the unquantified and quantified food frequency interview methods for measuring cholesterol intake on 4638 subjects from a multi-ethnic population in Hawaii. The methods were only modestly related, with product-moment correlation of 0.36 for men and 0.30 for women. The unquantified frequency method tended to yield a higher cholesterol value than did the quantified frequency method among lower level consumers, whereas the opposite was true for higher level consumers. These findings suggest that unquantified frequency methods cannot be used interchangeably with corresponding quantified frequency methods in studies of association between dietary cholesterol and disease occurrence. PMID- 4018992 TI - Drinking water source and mortality in US cities. AB - An apparent excess risk of all-cancer mortality among 473 of the largest US cities was found in relation to surface drinking water supplies. The increased risk for 100% surface water versus 100% ground water use was slight, about 2%, but statistically significant. This finding agrees with reports from several earlier studies in smaller geographical regions of the US, Great Britain and Canada. A relationship was further supported by the replication of this association within the larger of the 11 independent regions studied. Our data suggest that the association with surface water may be specific to cancer mortality. The increased risk would be expected to be greater than 2% if analyses were restricted to cancers of sites previously related to the use of surface drinking water. PMID- 4018994 TI - The reliability of reported suicide mortality statistics: an experience from Belgium. AB - To assess the reliability of official Belgian suicide statistics in epidemiological comparisons on national and district level, various mortality indicators for suicide, undetermined deaths, accidental poisoning deaths and 'estimated' suicide in 1968-1972 and 1978-1981 were compared. Results did not reveal important bias on national comparisons by underreporting. But the biased distribution of undetermined deaths among the 43 geographical entities (districts) suggests that the assumption about constancy of underreporting is not always met and has to be checked if possible. Nevertheless, the numerical weight of the underreporting categories was not found heavy enough to bias the geographical suicide pattern in Belgium. PMID- 4018993 TI - Mortality among New Zealand Maori and non-Maori Mormons. AB - Mortality rates for New Zealand Maori and non-Maori Mormons in the period 1970-77 have been compared with those for non-Mormons in the census year 1976 to measure the impact of the Mormon lifestyle on differences in mortality between Maoris and non-Maoris. Maori mortality was much lower among Mormons than non-Mormons suggesting that environmental, rather than genetic factors, play a predominant role in the relatively high overall Maori mortality. However the prevalence of smoking among Maori Mormons was not much lower than for the general Maori population. Reasons for the relative mortality advantage of Maori Mormons were therefore not clear, although attitudes to health and health services utilization, and the influence of strong social support networks, might be involved. Paradoxically, non-Maori Mormon mortality rates were similar to those for non-Mormons. A combination of factors appeared to contribute to this finding including the fact that 26% of non-Maori Mormons were of Pacific Island origin, non-Maori Mormons were of lower socioeconomic status than other non-Maoris, and part Maoris probably constitute a high, but unknown, proportion of Mormons classified as non-Maoris. PMID- 4018995 TI - Mseleni joint disease in 1981: decreased prevalence rates, wider geographical location than before, and socioeconomic impact of an endemic osteoarthrosis in an underdeveloped community in South Africa. AB - Mseleni joint disease (MJD), an endemic osteoarthrosis, was first described in 1970, localized to Kwa Zulu, South Africa. In 1981 another survey was conducted (1) to see whether prevalence had changed, (2) to estimate the prevalence in areas not previously surveyed and (3) to estimate its socioeconomic impact. A 5% stratified random sample of homesteads was selected and five local interviewers surveyed 333 kraals, interviewing 333 individuals, obtaining information on 3368 live members of these homesteads. Overall prevalence rates were 7.4% in 1566 females and 3.0% in 1179 males (age or sex unknown in 623). The previously affected area still had the highest prevalence rates, but they were significantly lower than before, even if only residents of at least ten years' duration were considered. These consistently lower age-specific prevalence rates are compatible with a decline in incidence rate, possibly because of disappearance of an environmental causal agent. Prevalence rates for females in some areas not previously surveyed were between 5 and 10%, suggesting that a larger area than stated before is affected. The proportions of severely disabled individuals are the same as reported in 1973 but greater in number considering the larger area affected. Of these, an estimated 67% of males and 47% of females are not receiving disability grants. Fifty per cent of children (aged 6-25 years) of affected parents have had no schooling compared with 30% of children of unaffected parents. This study also highlighted several methodological problems unique to rural research. It is suggested that while aetiological research should continue, the existing prevalence of MJD has major social, economic and health care implications, for which solutions should be researched as a high priority. PMID- 4018996 TI - The Swedish mortality pattern: a basis for health planning? AB - In response to new Swedish health legislation, which gives local county councils formal 'epidemiological' responsibility for the health of the whole population, the regional mortality pattern is presented here for the period 1969-78. The findings show that total mortality has decreased somewhat during the ten-year period, while at the same time the difference in life expectancy between men and women has increased to six years. The concept 'lost years before 65' is used as a measure of premature death. Suicide is the cause of death that has resulted in the greatest number of lost years among men as well as women. During the 1970's positive changes have come about for leukaemias, cervical cancers and motor vehicle accidents, changes that can be interpreted as being due to better treatment, increased screening and efficient prevention. On the other hand, failures are obvious when considering, for example, a twofold increase in premature alcohol-related mortality over the decade. The report also discusses the quality of mortality statistics as a basis for health planning. PMID- 4018997 TI - Guidelines for regional mortality analysis: an epidemiological approach to health planning. AB - In view of the epidemiological responsibility that the new Swedish health legislation gives to the local county councils, it has been increasingly necessary to identify and monitor the health status of the local population, eg the commune. As part of a large-scale collaborative project this paper focuses on problems of analysing regional mortality data and presents an attempt to deal with them by means of a systematic procedure. PMID- 4018998 TI - The physician/population ratio as a proxy measure of the adequacy of health care. AB - In the absence of service use and health status data at the individual level in most developing countries of the world, the utility of the physician/population ratio as a proxy measure of health service availability and use in health needs assessment is tested. Data from 60 predominantly developing countries show that the physician/population ratio is curvilinearly related to an indicator of population health status, namely infant mortality. When this relation is linearized by logarithmic transformations, the physician/population ratio accounts for 53% of the variance in infant mortality. There is no significant functional relationship between the physician/population ratio and infant mortality when state-level data in the US are analysed. Implications of these findings are discussed with respect to needs assessment in developing regions of the world. PMID- 4018999 TI - Seroepidemiology of hepatitis B in a population of children in central Tunisia. AB - The prevalence rate of HBV markers in the overall population was 18.0%. The prevalence rates of HBsAg and anti-HBs were 3.3% and 12.2% respectively. 2.5% of the children were negative for these markers but positive for anti-HBc alone. Of the 17 HBsAg positive children, 10 were HBeAg positive and four were anti-HBe positive. The statistical study using multifactorial correspondence analysis and the chi 2 test showed a positive relationship between the prevalence rate of anti HBs and age, and a negative relationship between the prevalence rate of 'absence of markers' and age. The male sex and urban dwelling were related to higher prevalence rates of HBsAg and anti-HBc alone and to a lower prevalence rate of 'absence of markers'. No relationship was found between geographical zone, father's education and HBV markers. The implications of these results in terms of prevention are discussed. PMID- 4019000 TI - A regression approach to the analysis of data arising from cluster randomization. AB - A generalized least squares regression approach is proposed for the analysis of data arising from experimental studies involving cluster randomization and non experimental studies in which the major treatment factor corresponds to a characteristic which applies at the cluster level. This approach is more flexible than that provided by the analysis of variance, and unlike ordinary least squares, provides significance levels which are adjusted for the correlation among elements within the same cluster. Two examples are presented. PMID- 4019001 TI - Risk factors for coronary heart disease in rural Hungary. AB - This is a ten-year study of a cohort of 1088 Hungarian men aged 40-59 at entry, with a 99% baseline response rate and complete ascertainment of cases and follow up. The methods were state of the art for the period the survey was performed, with quality control for standard procedure and training. Zero, five- and ten year examinations were carried out and standard risk factors measured and analysed in relation to the ten-year experience, ie, age, blood cholesterol, blood pressure, smoking, body mass, vital capacity, and skinfolds. Risk factor levels were high relative to the Mediterranean and Oriental populations in the Seven Countries Study. The five-year coronary heart disease rates were intermediate between the low rates in Yugoslavia and Greece and high rates in Finland. Ten-year events were significantly and linearly related to quintile values of serum cholesterol and of 3, 4, 6, and 9 risk factors in the Walker Duncan logistic model. Discrimination was not substantially improved beyond three factors apart from age. The maximal prediction concentrated 62% of events in the upper 20% of multifactor risk, and up to 80% in the upper 40% of risk. The authors conclude, from this separate but comparable study to the Seven Countries Study, that the results are not greatly different from that study or from the US Pooling Project. Unique features of the study, and its results, are the eastern European population, the absence of a strong CHD relationship with smoking, and the strong independent relationship with body mass. PMID- 4019002 TI - Association between parental and student smoking behaviour in a Brazilian medical school. AB - In a 20% random sample of University of Brasilia medical students no association was found between student and parental smoking behaviour. A low prevalence of habitual smoking (14.0%) and a low mean daily cigarette consumption (8.9 cigarettes per smoker, per day) characterized this population. PMID- 4019003 TI - Acute appendicitis not associated with social class among children. AB - Acute appendicitis has previously been found to be associated with social class. In an attempt to confirm this, 125 patients with histologically verified acute appendicitis were compared with 1802 control children, randomly selected from the schools of the City of Helsinki. Social class determination was based on father's occupation in families with two parents, and on mother's occupation in single provider families. No association with social class was found. The proportion of single provider families was around 25% among both cases and controls. Appendicitis patients are one potential source of control groups in epidemiological studies. PMID- 4019004 TI - Selenium and cardiovascular disease. PMID- 4019006 TI - Maternal mortality in developing countries. PMID- 4019005 TI - Epidemiology as the basis for clinical and social policy decisions. PMID- 4019007 TI - Lymphomas, cancer of bladder, colon and prostate in Lebanon: an epidemiological challenge. PMID- 4019008 TI - Appendiceal carcinoma metastatic to the ovaries and mimicking primary ovarian tumors. AB - Primary appendiceal carcinomas are a rare source of metastases to the ovaries. Three cases are reported here, and 25 others are reviewed from the English literature. The recognition of this entity is important, since the metastases may mimic an ovarian primary tumor clinically, and because of the propensity for a recognized appendiceal carcinoma to relapse in the ovaries. Therapeutic implications dictate that the appendix should always be carefully examined during exploration for ovarian masses, and prophylactic appendectomy should be considered, as part of the treatment of ovarian carcinomas. PMID- 4019009 TI - Endometrial carcinoma: nontumor factors in prognosis. AB - The clinical records and pathologic specimens from 150 patients with endometrial carcinoma were reviewed to test the hypothesis that constitutionally predisposed patients with evidence of endogenous hyperestrinism (i.e., obesity, hypertension, diabetes, nulliparity, leiomyomata, adenomyosis) have a more benign form of carcinoma than do patients who do not fit this profile. Our results do not support this hypothesis, but do reveal certain other prognostic indicators, in addition to factors relating to the tumor itself, including stage, grade, histologic type, and extent of invasion. These indicators include: (a) age and menopausal status--women over 50 years of age, and more impressively, postmenopausal women of any age, have less favorable histology, staging, and survival; (b) race--black women have higher-grade tumors, higher-stage tumors, and poorer survival rates than white women; (c) hyperplasia--when hyperplasia is found in the biopsy, curettage, or hysterectomy specimen, the accompanying carcinoma is of a much more favorable type and extent, and survival rates are significantly better. The reasons for these correlations are not fully understood, and possible explanations are discussed. There may be two distinct patterns of endometrial carcinoma: a prognostically favorable one arising on a background of hyperplasia predominantly in premenopausal women, and a prognostically unfavorable one, occurring principally in postmenopausal women without hyperplasia. Empirically, we advise pathologists to comment on the presence or absence of hyperplasia in any specimen in which endometrial carcinoma is diagnosed. PMID- 4019010 TI - Ultrastructural features of primary trabecular carcinoid tumor of the ovary. AB - A case of primary trabecular carcinoid tumor of the ovary in a 48-year-old woman is reported. Histologically the tumor showed typical appearances associated with this neoplasm and was composed of long ramifying and anastomosing cords, ribbons, and trabeculae made up of uniform epithelial cells surrounded by connective tissue stroma. Occasional cells showed orange and red-brown granules in the cytoplasm. A number of cells were argyrophil-positive and occasional cells showed argentaffin positivity. The trabecular carcinoid was associated with mature cystic teratoma (dermoid cyst). Ultrastructurally the trabecular carcinoid was composed of light and dark cells with poorly formed basal lamina. Both types of cell contained membrane-bound neurosecretory granules which were round or oval, varied in size, but uniform in shape. The histological appearances of the tumor and of the neurosecretory granules distinguish trabecular carcinoid from other types of carcinoid tumors of the ovary and other ovarian neoplasms. PMID- 4019011 TI - Sertoli-Leydig cell tumor of the ovary. PMID- 4019012 TI - The second-look operation for ovarian neoplasms: a study of 85 cases emphasizing cytologic and histologic problems. AB - This study reviews the clinical, cytologic, and histologic findings in 85 female patients who underwent a "second-look" exploratory laparotomy to evaluate the response to therapy for primary ovarian malignancies. Most patients had no evidence of clinically active disease at the time of the follow-up surgical procedure, and, therefore, the results of the multiple biopsies and cytologic studies were paramount in the decision to continue or withhold additional treatment. Unequivocally positive or negative findings were obtained in 64% of cases. In the remaining 36% of cases, there was a spectrum of atypical cytologic and/or histopathologic features with sufficiently disturbing aspects as to raise questions about the differential diagnosis. PMID- 4019013 TI - Cholesterol metabolism in lean and obese Zucker rats: effects of portacaval anastomosis. AB - The effects of portacaval anastomosis (PCA) on cholesterol biodynamics of male adult (fa/fa) Zucker rats and their lean littermates were studied with an isotopic equilibrium method. Animals were fed with a sucrose-rich semi-purified diet. Obese rats were hypercholesterolemic (2.03 +/- 0.14 vs 1.06 +/- 0.7 mg/ml), had a cholesterol-enriched liver (135.3 +/- 14.5 vs 40.0 +/- 2.6 mg/liver) and accumulated cholesterol in body pools. However no difference in the rates of cholesterol absorption, synthesis, fecal elimination or transformation into bile acids distinguished obese from lean Zucker rats. In both lean and obese rats, PCA decreased cholesterolemia by about 28 per cent and liver weight by 40 per cent while the total cholesterol content of the liver was not affected. Input of synthesized cholesterol (internal secretion) was strikingly decreased by the shunt (from 13.2 +/- 0.6 and 12.6 +/- 0.7 mg/day/rat before PCA, to 8.9 +/- 0.8 and 8.6 +/- 1.0 mg/day/rat after PCA) in lean and obese rats respectively. A similar decrease was observed in the cholesterol transformation into bile acids. Since the activity of the gut for cholesterol synthesis, as shown by the fecal external secretion (cholesterol synthesized by the gut and directly eliminated in the gut and feces) was probably not modified, the reduction of internal secretion induced by PCA resulted from decreased hepatic cholesterogenesis. It is suggested that this decrease may be one of the factors involved in the lowering effect of PCA on plasma cholesterol level. PMID- 4019014 TI - The effect of vigorous treadmill exercise on adipose tissue development in the Zucker rat. AB - Four-week-old male lean and obese Zucker rats were subjected to intense daily exercise for a 10-week period. The exercise regimen used (running 6 days/week for 90 min/day on a treadmill at 1.3 Km/h at an 8 per cent grade) was designed to maximize the amount of exercise performed. Lean and obese runners (LR and OR) gained significantly less weight than sedentary controls (LS and OS). Food intake was lower in LR and unchanged in OR compared with control animals. Exercise increased adrenal weight in runners of both phenotypes. Gastrocnemius muscle weight was significantly higher in OR compared to OS. Despite the intense exercise regimen, carcass fat of OR was reduced only 12 per cent versus OS. In contrast, exercise decreased carcass fat by 32 per cent in LR versus LS. This decrease in body fat of LR was due to smaller adipocytes. Exercise did not affect adipocyte size in obese rats. However, OR had fewer carcass adipocytes. These results indicate that exercise had substantially different effects on adipose tissue cellularity of lean and obese rats. The results of the present study indicate that a program of intense treadmill exercise initiated immediately post weaning only modestly reduced adipose tissue growth in obese Zucker rats. Furthermore, it did not normalize body composition. PMID- 4019015 TI - Genotype identification of 10-day old Zucker rats by lipid content of inguinal fat pad. AB - Surgical biopsies of the inguinal fat pad were performed on 35 fa/fa and 40 Fa/fa pups, aged 10 days, from eight litters. The lipid content of the pad, expressed as a percentage of the mean in each litter, allowed a 100 percent reliable prediction of the genotype. In three of the eight litters, we compared this method with that based on the frequency distribution of adipocyte size. PMID- 4019016 TI - Glycerol release from incubated human adipocytes is not affected by gastrointestinal peptides. AB - There is evidence for involvement of gastrointestinal hormones in pathogenesis of obesity and reports on lipolytic activity in animals. The in vitro lipolytic activity of these hormones was tested in human adipocytes. Vasoactive intestinal polypeptide, glucagon, secretin, human gastrin I, gastrin releasing polypeptide, gastric inhibitory polypeptide, pancreatic polypeptide, motilin, bombesin, neurotensin, C-peptide, as well as cholecystokinin did not stimulate lipolysis significantly above basal. These results indicate that the involvement of these hormones in obesity in man might not be due to a direct lipolytic effect on the human adipocyte. PMID- 4019017 TI - Diet and exercise training effects on resting metabolic rate. AB - The decline in resting metabolic rate (RMR) during periods of caloric restriction is a well documented phenomenon. The purpose of this study was to determine if either 30 min of daily self-selected aerobic activity (Group D) or prescribed exercise training performed every other day (Group P) for 12 weeks can prevent the decrease in RMR during caloric restriction for weight loss. Seventy-eight adult subjects (38 M, 40 F) whose weights were 15-35 percent above the upper limit for age, sex and frame were randomly assigned to three treatment groups. All three groups followed the same 1200, 1500 or 1800 kcal/d (5023, 6279, 7534 kJ) diet exchange plan. Group C (Control) followed no exercise program, while D and P exercised as described above. Maximal oxygen consumption (VO2 max, m10(2)/kg X min-1) predicted from the Bruce Test increased by 0.08 +/- 7, 9 +/- 12 and 12 +/- 9 percent in groups C, D and P, respectively. The increases for D and P were significantly higher than for C (P less than 0.01). RMR (m10(2)/kg X min-1) increased by 2 +/- 9, 4 +/- 7 and 10 +/- 9 percent in groups C, D and P respectively. The percent change for group P was significantly greater than that for groups C and D (P less than 0.05). There was a significant relationship across all subjects between the % delta in VO2 max and % delta in RMR (r = 0.307, P less than 0.01). However, the association between these two variables was stronger for females than for males.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4019018 TI - Assessment of methods for assigning treadmill exercise workloads for lean and obese women. AB - The use of relative oxygen consumption (% VO2 max) to equate workloads between trained and untrained subjects is considered appropriate. Whether this method (% VO2 max) is correct when testing lean versus obese subjects has not been studied. Using three experimental sessions separated by at least one week we studied seven obese, nondiabetic women weighting 140 +/- 21 kg (mean +/- s.d.) and 10 lean women of similar age weighing 51 +/- 5 kg during treadmill walking. Body fat determined by hydrostatic weighing was 50 +/- 7 and 23 +/- 7 percent in obese and lean groups, respectively (P less than 0.05). Absolute maximal VO2 (VO2 max) in obese women (3.18 +/- 0.28 l/min) significantly exceeded VO2 max for lean women (2.45 +/- 0.31 l/min, P less than 0.05). However, in obese women VO2 max relative to total body weight (TBW) was lower (P less than 0.05) while VO2 max relative to fat-free weight (FFW) was similar to corresponding values for lean women. Submaximal treadmill exercise at 75m/min with 0, 5 and 10 percent inclines resulted in higher VO2 (l/min) and heart rate (HR) in the obese group (P less than 0.05). At each incline VO2 relative to BW was significantly lower in the obese (P less than 0.05) yet significantly higher when expressed relative to FFW (P less than 0.05). The relationship between HR and %VO2 max was similar for lean and obese. Ten minutes of walking at 70% VO2 max resulted in no significant differences between the groups in the 10 min values for HR, total work done, rise in rectal temperature, plasma lactic acid, perceived exertion and oxygen consumption relative to FFW. We conclude that either fixed absolute workloads or fixed oxygen consumption (absolute or relative to BW or FFW) are inappropriate methods for equating workloads when lean and obese subjects are compared. Relative VO2 accurately defines physiologically comparable exercise intensities for these groups and this should be the method of preference when studies are designed to investigate metabolic, endocrine or cardiovascular similarities and/or differences between these groups. PMID- 4019019 TI - Basal metabolism of obese adolescents: age, gender and body composition effects. AB - Body composition (percent fat and lean body mass) and basal metabolic rates were determined in 67 obese adolescents ranging in age from 10 to 16 years (30 male, 37 female). Basal oxygen uptake was determined on rising in the morning using open-circuit spirometry with a 10-min collection period. Body composition was determined from body density measurements using the underwater weighing procedure. There were no male-female differences (except for basal VCO2 production, P less than 0.05) for any body composition or metabolic variable. The subjects' (male and female) average weight was 73 kg, height--157 cm, percent fat -40 percent, fat weight--30 kg, lean body mass--92 kg, and kcal/24 h--1535. Correlations between age, body composition and basal energy expenditure were all moderate to low (r less than or equal to 0.78). In contrast to adult data, lean body mass was not highly correlated to basal energy expenditure suggesting that perhaps there is a 'metabolic condition' of the obese adolescent modulated by excess fatness or the instability of the body cell mass. Stepwise multiple linear regression revealed that for the obese male adolescent, body surface area and percent fat, and for the obese female adolescent body surface area and body weight resulted in the best prediction of basal kcal/24 h. The standard errors of prediction were +/- 17.9 percent for the males, and +/- 14.4 percent for the females. PMID- 4019021 TI - Spectroscopic study of the interaction of gossypol with bovine serum albumin. AB - The interaction of gossypol with bovine serum albumin (BSA) at pH 7.6 in 0.02 M borax-borate buffer has been followed by circular dichroism (CD) and difference spectroscopy. From the extrinsic CD band at 390 nm, a binding constant of 2.7 X 10(3) M-1 was calculated. At 54 degrees the induced CD spectrum was abolished, suggesting that the interaction is not favoured at that temperature. The effect of various solvents and salts on the interaction has been followed by difference spectroscopy. The modification of epsilon-amino groups of lysine did not affect the interaction. Binding of gossypol to BSA does not cause a change in its secondary structure or sedimentation coefficient. PMID- 4019020 TI - Conformation of the eosinophil chemotactic tetrapeptides and analogues in dimethyl sulfoxide. 1H n.m.r. studies. AB - Proton nuclear magnetic resonance parameters are reported for DMSO-d6 solutions of the eosinophil chemotactic tetrapeptides, Val1-Gly2-Ser3-Glu4 and Ala1-Gly2 Ser3-Glu4, as well as three analogues of the Val1 tetrapeptide, D-Val1, Ala2 and Ala3. The synthesis of Val-(S)-[alpha-2 H1] Gly-Ala-Glu, in which the glycine has been stereospecifically deuterated in the H alpha 3 position, has allowed the assignment of the 1H resonances belonging to individual H alpha 2 and H alpha 3 glycine methylene protons. Simulation of the glycine ABX spin system yields two vicinal coupling constants which are consistent with a highly preferred conformation about the glycine HN-C alpha bond. The chemical shifts, coupling constants, temperature coefficients of amide proton chemical shifts and calculated side chain rotamer populations are reported for all peptides. The coupling constant analysis and temperature coefficients of amide proton chemical shifts together suggest that a type I beta-turn conformation is preferred by the Ala3 analogue. The 1H n.m.r. parameters of the other peptides suggest that these can also adopt a beta-turn conformation in DMSO. There are, however, considerable differences in the extent of conformational averaging undergone by the various peptides. PMID- 4019022 TI - Conformation and stability of the chymotrypsin inhibitor from winged bean seed (Psophocarpus tetragonolobus (L.) DC). AB - Spectrophotometric measurement was found to be a sensitive method for evaluating the stability of the chymotrypsin inhibitor from the winged bean. The thermal stability of this protein in aqueous solution was much greater at pH 3 than at pH 8 or pH 11. Evidence from u.v. absorption and from circular dichroism indicated that irreversible conformation changes occurred at higher temperature (greater than 70 degrees). Circular dichroism and optical rotatory dispersion studies at pH 8 show that the inhibitor is rich in beta-structure and virtually devoid of alpha-helix in aqueous solution. We conclude from experiments with denaturing solvents that the inhibitor is very stable and that high concentrations of denaturant are required before unfolding occurs. Chemical modification experiments with tetranitromethane were consistent with a tight stable structure; even in 6M guanidine hydrochloride only three of the five tyrosine residues in the inhibitor molecule were nitrated. However, tyrosine does not seem to be implicated at the reactive site of the inhibitor. Interaction of the inhibitor with alpha-chymotrypsin and chymotrypsin B was also followed by difference spectroscopy in the ultraviolet region. Difference spectra were detected that were characteristic of changes in the environment of both tyrosine and tryptophan chromophores. Comparison of the spectral data obtained for the interaction of the inhibitor with bovine alpha-chymotrypsin and with chymotrypsin B indicated that a tryptophan residue may be involved at the reactive site of the inhibitor. Spectral changes were also detected for the interaction between the chymotrypsin inhibitor and trypsin, although it is well established that the specificity of this inhibitor is restricted to the chymotrypsins.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4019023 TI - HPLC-studies on nonmercapt-mercapt conversion of human serum albumin. AB - Human mercaptalbumin (HMA) and nonmercaptalbumin (HNA) could be separated by high performance liquid chromatography (HPLC) at neutral pH. Using HPLC, the present authors found the nonmercapt-mercapt conversion (HNA----HMA) during hemodialysis and the mercapt-nonmercapt conversion (HMA----HNA) after hemodialysis in chronic renal failure, indicating HMA as the covalent carrier protein for sulfur containing amino acids. PMID- 4019024 TI - Utilization of 1-hydroxybenzotriazole in mixed anhydride coupling reactions. AB - The coupling of Boc-Val-OH to either H-Pro-OBzl or H-Pro-Gly-Val-Gly-OBzl by the mixed anhydride method leads to the formation of a urethane by-product in yields of 40-60%. This side reaction can be suppressed by the addition of HOBt to the reaction mixture before the amino component is added. This results in a substantially increased yield of the desired peptide. PMID- 4019025 TI - Solid phase synthesis of two cholera toxin B subunit antigens. AB - The 30-50 and 50-75 sequences of the cholera toxin beta chain including the amino acids that are thought to be involved in toxin-receptor binding have been synthesized using the solid phase method. They were then purified by gel permeation and ion exchange chromatography. Both these free peptides induced serum antibodies recognising the native toxin after oral or intraperitoneal administration. Only the antibodies raised against the 50-75 peptide, however, were able to neutralize toxin activity. PMID- 4019026 TI - Self-association and solubility of peptides. Solvent-titration study of protected C-terminal segments of porcine secretin. AB - Self-association of peptides (related to the C-terminal sequence of porcine secretin) in methylene chloride was disrupted by adding dimethylsulfoxide in increasing amounts. This structural transition was monitored by the disappearance of the amide-I C = O stretching band of strongly intermolecularly hydrogen-bonded molecules (1625-1630 cm-1) in the infrared absorption spectra. The effects induced by main-chain length and sequence, type of N alpha-protection, and concentration were assessed. Hexamethylphosphortriamide was compared for its structure-disrupting properties to dimethylsulfoxide. The increasing propensity to aggregate displayed by these peptides is paralleled by a decrease in their solubility. The impact of these results on the planning of peptide syntheses is briefly discussed. PMID- 4019027 TI - Anti-writhing activity of some peptides related to neurotensin and tuftsin. AB - Several small peptides related to neurotensin (NT) and tuftsin were synthesized and tested for analgesic activity against acetic acid induced writhing in mice. None of the peptides approached the activity shown by NT or NT hexapeptide. Tuftsin itself was found to be weakly active. An isosteric dipeptide related to a cobra venom peptide was found to have considerable anti-writhing activity at a high intracerebroventricular dose. PMID- 4019028 TI - Cyclic peptides. XIX. Synthesis, conformation, and biological activity of cyclo( Pro-Val-Pro-Val-) with L-L-L-L and L-D-L-D sequences. AB - cyclo(-L-Pro-L-Val-L-Pro-L-Val-) (1L) and cyclo(-L-Pro-D-Val-L-Pro-D-Val-) (1D) were synthesized by the conventional method for peptide synthesis. Conformations of 1L and 1D in solution were studied. Compound 1L has a cis-trans-cis-trans backbone conformation with C2 symmetry in CDCl3. This conformation is slightly different from that in crystalline state and in DMSO-d6 solution. Compound 1D has a cis-trans-cis-trans conformation in DMSO-d6 and an all-trans conformation in trifluoroethanol-d3. Compound 1L retarded stem-growth of rice seedlings and, in contrast, compound 1D promoted root-growth of rice seedlings. PMID- 4019029 TI - Crystal structure and conformation of the cyclic tetramer of a repeat tripeptide of elastin, cyclo(L-valyl-L-prolylglycyl)4. AB - X-ray diffraction data were used to determine the crystal structure of cyclo-(L Val-L-Pro-Gly)4, the cyclic tetramer of a repeat tripeptide of elastin. The crystals are monoclinic, space group C2, with a = 29.639(3), b = 7.099(1), c = 20.325 (2) A, and beta = 130.4(4) degrees. The structure was solved by direct methods and refined by least squares to R = 0.082 for 2603 observed reflections. The cyclic dodecapeptide contains two beta (II) turns. Hydrophilic and hydrophobic channels that run parallel to the b axis are formed by the stacking of cyclic peptides on twofold axes. PMID- 4019030 TI - Sidechain and backbone potential function for conformational analysis of proteins. AB - An improved potential function has been devised for the calculation of protein conformations. Each amino acid residue is represented by two points. The mainchain is traced by the sequence of C alpha atoms, and the details of sidechain structure and interactions are represented by a representative sidechain atom. This potential function has been developed from a data base of 22 high resolution protein crystal structures and includes the components of an earlier potential developed from a similar data base where each amino acid residue is represented by only its C alpha atom. In virtually all aspects of testing, the present potential betters the previous single-point potential, and is shown to be useful in the simulation of protein folding. PMID- 4019031 TI - Chemical modification of canavanine with p-nitrophenylglyoxal. Factors influencing the chemistry and reactivity of alpha-dicarbonyl-guanidino reactions. AB - The role of structural features and deprotonation of guanidino derivatives on chemical reactions with p-nitrophenylglyoxal has been investigated. Canavanine, an arginine analog, reacts to form a yellow product, which absorbs maximally at 350 nm (epsilon = 6500) and at 278 nm (epsilon = 14 500). Elemental analysis, fast atom bombardment mass spectral analysis, n.m.r. and i.r. studies suggest that the product is a 5-(p-nitrophenyl)4-oxo-2 imidazoline derivative of canalaline. Kinetic studies show that the second order rate constant for the reaction increases with increasing pH in the range of pH 7-11.0. It is concluded that the pH dependence of the reaction can be explained by general base catalysis and not simply by a deprotonation of the guanidinoxy side chain. The reaction of arginine, polyarginine, and other derivatives differs markedly from that of canavanine. The results suggest that change in the tautomeric equilibria between the imino and amino forms of the guanidino group may partly account for differences in reaction of canavanine and arginine and the reactions of specific arginyl residues in proteins. PMID- 4019032 TI - Synthesis and opioid activity of partial retro-inverso analogs of dermorphin. AB - We studied the effect of partial retro-inverso modification of selected peptide bonds of dermorphin (H-Tyr-D-Ala-Phe-Gly-Tyr-Pro-Ser-NH2. The modifications concern two consecutive peptide bonds (Phe3-Cly4-Tyr5, I) or a single one (Gly4 Tyr5-, II or Phe3-Gly4, III). All pseudoheptapeptides showed low opioid activity in the in vitro and in vivo tests. Compound III has a biological potency comparable to that of morphine but only 2-5% of original dermorphin when tested in guinea pig ileum preparation and in mice tail-flick assay after intracerebro or subcutaneous administration. PMID- 4019033 TI - Mechanism of the reaction catalyzed by acyl-CoA: lysolecithin acyltransferase from rabbit lung. pH studies and chemical modification. AB - This paper deals with the first attempt to elucidate the chemical mechanism of acyl-CoA: lysolecithin acyltransferase from rabbit lung, a key enzyme in the metabolism of lung surfactant. For this purpose, the pH dependence of kinetic constants as well as the chemical modification of the protein have been studied on a partially-purified preparation. From these experiments, the pKs on which the activity of the enzyme relies have been calculated, giving values of pK1 congruent to 5.5 and pK2 congruent to 10. Analysis of the effect of organic solvents on these pKs and the calculation of the enthalpies of ionization, together with the chemical modification experiments, lead to the conclusion that pK1 is due to an histidine residue, whereas pK2 arises from the amino group of the adenine ring of palmitoyl-CoA. Moreover, chemical modification demonstrated an essential cysteine. A tentative chemical mechanism, in accordance with these results, is proposed and it is hypothesized, in view of other results obtained in our laboratory and from the literature, that the chemical mechanism of acyl transfer to sn-2 position may be common to other enzymes of glycerolipid metabolism. PMID- 4019034 TI - Preferential cleavage at aspartyl-prolyl peptide bonds in dilute acid. AB - A simple, rapid technique is presented for preferential cleavage at aspartylprolyl peptide bonds. The method is based upon the fact that these peptide bonds are 8-20-fold more labile in 0.015 N HCl at 100-110 degrees than other aspartyl-X or X-aspartyl peptide bonds. The method has proven effective in the cleavage of several peptides from pig kidney fructose-1,6-bisphosphatase and should facilitate sequence analysis of proteins that contain aspartyl-prolyl linkages. PMID- 4019035 TI - Critical analysis of visual function evaluating techniques in newborn babies. AB - The most widely-used techniques for testing visual function in babies are reviewed. Advantages and limitations of optokinetic nystagmus testing, visual evoked responses and preferential looking techniques are considered. The theoretical basis and the clinical applicability of those techniques are outlined. Other simple methods are considered as well, which allow practicing ophthalmologists to assess the presence or absence of vision in babies. The importance of early diagnosis for prevention and treatment of visual deficits in babies is stressed. PMID- 4019036 TI - Amacrine and horizontal cell dysfunction in adult ceroid-lipofuscinosis (Kufs disease) and anatomical correlates in the ovine model. AB - Psychophysical examination of the visual performance of a patient with Kufs disease suggests abnormal functioning of the amacrine and horizontal cell systems of lateral inhibition. The sheep model offers insight into early patho-physiology of these cell types. PMID- 4019037 TI - Glaucoma in China. AB - The motivation for this paper is that, having come from China, a country which had closed herself to the outside world for three decades, I thought it might be interesting to compare glaucoma in the two countries. Since I am from only a municipal hospital of a small city Hangzhow (a sister city of Boston), whatever I say can only be accepted as personal view points. Presently I have this wonderful opportunity to be a research fellow at the world wide famous Massachusetts Eye & Ear Infirmary, which is affiliated with Harvard Medical School. The comparison therefore may not be exactly appropriate but may help to see where my country stands, what we have, what we lack and what goals to strive for to better the health of China. There may be some confusing terms in this paper such as 'Liberation', 'Cultural Revolution', etc. Table 1 may help give a clearer conception. PMID- 4019038 TI - Comparing continuous and stepwise luminance variation in static campimetry using the Grignolo-Tagliasco-Zingirian projection campimeter. AB - In traditional static perimetry the remarkable precision achieved, resulting mainly from the lack of temporal factors related to latency, largely makes up for the relatively long time required to perform the test. Conversely, the increase in speed of the test and in the information content of the visual field charts counteract the lower precision attained with kinetic perimetry. If the influence of the latency time on responses could be kept at a low value, then adopting a static strategy, based on a continuous rather than discrete target luminance variation for threshold detection, could be justified. For this purpose a luminance variation time sequence designed to reproduce the conditions of the traditional static perimetric test was chosen. The test was performed on the Grignolo-Tagliasco-Zingirian projection campimeter, after comparing its clinical performance with the Goldmann perimeter. These two methods - one based on continuous variation, the other based on discrete target luminance variation - were compared using a 14-subject sample. We conclude that the presentation strategy based on continuous luminance variation can be regarded as a valid alternative to the traditional method. PMID- 4019039 TI - Narcissism: its structures, systems and affects. AB - The growth of object relationships may be studied along either the developmental line of the discharge-object or that of the reflexive-object. The former is the well-known line of development from the need-satisfying object to the constant object and is a study of id-ego relationships. The developmental line of the reflexive-object, on the other hand, follows the history of the introjects and is a study of either ego-superego or ego-ego ideal relationships. It is the latter which constitutes the study of narcissism. The development of the ideal ego out of the ego nuclei leads eventually to the child's struggle to maintain a sense of omnipotence and to the narcissistic crisis. Out of this struggle the introjection of the idealized mother occurs which, as the ego ideal, continues the systemic line of development of narcissism. Various narcissistic states and affects such as shame, humiliation, depression, grandiosity, pomposity, arrogance, adoration and enthralment are the result of either hypercathexis of the introjects of the ego ideal (or of persisting remnants of the ideal ego) and the resulting conflict with the ego, or hypocathexis of the introjects and resulting dormancy of the system ego ideal. PMID- 4019040 TI - Working through in the countertransference. AB - This paper is intended as a development of Strachey's classic paper 'The nature of the therapeutic action of psycho-analysis'. Strachey states that the full or deep transference experience is disturbing to the analyst; that which the analyst most fears and most wishes to avoid. He also stresses that conveying an interpretation in a calm way is necessary. The area addressed is the task of coping with these strong countertransference experiences and maintaining the analytic technique of interpretation. The clinical illustrations attempt to show something of the process of transformation or working through in the analyst, as well as showing that the patient is consciously or unconsciously mindful as to whether the analyst evades or meets the issues. The contention that the analyst is not affected by these experiences is both false and would convey to the patient that his plight, pain and behaviour are emotionally ignored by the analyst. It is suggested that if we keep emotions out, we are in danger of keeping out the love which mitigates the hatred, allowing the so-called pursuit of truth to be governed by hatred. What appears as dispassionate may contain the murder of love and concern. How the analyst allows himself to have the experiences, work through and transform them into a useful interpretation is the issue studied in this paper. PMID- 4019041 TI - The psychoanalytic point of view: basic concepts and deviant theories. A brief communication. AB - This paper probes the meaning of deviant theories in psychoanalysis and sketches in the psychoanalytic point of view with the intent of providing a background for further discourse in the interest of creative advances in the field. PMID- 4019042 TI - Narcissistic organization, projective identification, and the formation of the identificate. AB - Clinical examples are given, varying from what would appear to be self-sufficient normal people, to overtly psychotic cases, in order to illustrate the development of a narcissistic organization of varying intensity and permanence. That is to say, an identification via projective identification has taken place, which heightens intrinsic omnipotence, to allow what has been termed the identificate to believe that it has become the desired object--and thereby that within this spuriously organized ego-structure exist the characteristics and functions of the object or part object that has been taken over. Varying forms of such identificatory process are illustrated. The functions of these 'successful defence' manoeuvres are to obviate any feelings of an awareness of envy, although they may be overtly envious attacks within themselves, secondly they nullify any awareness of dependence, and also nullify awareness of need and illness, and thirdly they maintain the narcissistic organization by producing a successful identificate. PMID- 4019043 TI - On repetition. Its relationship to the depressive position. AB - Thinking is painful as it progresses. Something of what is being achieved has to be left behind. The loss is being compensated by repetition in variations, as if the unconscious tries to restore what has been left behind. Looking back on the steps of thinking, one gains a feeling of security in one's conclusions if these steps are restored. PMID- 4019044 TI - Nosography and theory of the schizophrenias. AB - A theory of the schizophrenias must take account of the varieties of symptomatology and courses of illness which occur. Neglect of nosography has led to controversy about object relations in the schizophrenias. At the onset of all schizophrenic psychoses real object relations are replaced by 'psychotic' identifications. The object is retained despite its regressed state. Absence of remission and courses to end states can be attributed to loss of the object. This leads to delusional object relations based on fantasy. PMID- 4019045 TI - Important associations among EEG-dynamics, event-related potentials, short-term memory and learning. AB - Averaged and single sweep auditory event-related potentials (ERPs) were analysed in the time and frequency domain to demonstrate a dynamic, functional relationship between prestimulus EEG activity and poststimulus ERP changes. Evidence is presented of prestimulus "preparation changes" which were elicited by the presentation of regular, frequent target tones. The development of preparation changes was associated with prestimulus EEG synchronisation, frequency selective phase alignment at the point of stimulation and a greater predictability of the poststimulus response to target and nontarget tones. Time varying responses to target and nontarget tones are described for different experimental conditions and related to preparation rhythms. The mechanisms and possible neural correlates of the endogenous P300 change are discussed. The findings from this study and other relevant investigations have been used to formulate hypotheses about the relationships among preparation changes, ERPs and short-term memory, habituation and learning. PMID- 4019046 TI - Does frequency analysis lead to better understanding of human event related potentials. AB - A combined analysis procedure was used to study auditory, sensory evoked potentials (EPs) and event-related potentials (ERPs) in human subjects. Single sweep and averaged data were analysed in the time and frequency domains. Recognised peaks, seen in the averaged data, were related to specific poststimulus changes within conventional delta, theta and alpha frequency bands. The potential advantages of single sweep analysis, selective averaging and frequency domain analysis are discussed. The importance of studying prestimulus EEG activity in order to understand poststimulus changes is emphasised in relation to proposed hypotheses concerning brain dynamics and evoked response mechanisms. Specific frequency changes, elicited by target tones in auditory "odd ball" experiments, are described and contrasted to changes seen in EPs and nontarget ERPs. Our findings suggest that the P300 change of averaged data is the later consequence of poststimulus frequency changes which can be detected within the first 100 msec. The practical implications of our findings are briefly discussed. PMID- 4019047 TI - Human evoked potentials and C-fiber pain. AB - An evoked potential report by four authors has revived the question of the somatosensory specificity of the vertex potential of somatosensory evoked potentials, when these are derived by scalp conductance in response to subjectively painful skin stimulation. By a peripheral nerve-block maneuver combined with subjective sensoriperceptual reports, the authors show a late, slow positive wave in the somatosensory evoked potential whose appearance and disappearance are claimed to reflect the brain's response to a uniquely C-fiber input and to a combination of A delta and C-fiber input respectively. But their idiosyncratic interpretation of their data has merely revived an unresolved question: How much, if anything, of these familiar "ultralate," slow positivities can be ascribed to any form of neural encoding of nociception, as distinct from a nonspecific brain response to a behaviorally important stimulus? PMID- 4019048 TI - Event related aspects of somatosensory and auditory evoked potentials: noise or signals? AB - The so-called Vertex Potential (VP) of human scalp-conducted and event related brain potential (ERBP), which occur as a slow and often large, biphasic sinusoid within the 100-400 msec time segment after transient stimulation in the three main sensory modalities, are the longest researched of all human evoked potential (EP) phenomena. Its variable amplitude has been directly correlated, in experiments expressly tailored for the purpose, with input/output variables such as the rate of acceleration of given stimulus parameters from a state of relative rest (RM function), interstimulus interval (ISI), stimulus intensity, skin potential and resistance changes (SPR and SRR), the peripheral electroneurogram (ENG), and experimentally isolated C-fiber afference; and with neuropsychological variables such as attention or vigilance, visual acuity, response time, subjective stimulus probability or expectancy, acute pain of both fast and slow kinds, intelligence quotient (IQ), and psychometric personality scores (e.g., extraversion versus introversion and neuroticism versus normality). Unfortunately, the cerebral, neural origins of the VP, if any, are unknown; it is reported as usually absent from cortex-surface EP in those primates and mammals hitherto studied, and also from human extracranial event related magnetic fields of the brain (ERMFb) insofar as these reveal only superficial tangential sources; but a possible analog has been recorded from deep subcortical electrodes during human neurosurgery. In view of the increasing published range and quantity of direct correlates of VP amplitude, and of the scarcity of data about its neuroanatomy and neurophysiology, it seemed a good idea to do some rudimentary signal analysis. Preliminary results from five subjects confirm earlier data: The VP of somatosensory (SEP) and auditory (AEP) evoked potentials, as obtained by scalp-conductance and either averaged or single-epoch, can be resolved into inconsistently stimulus synchronized frequency components which are also present as relatively unsynchronized waves in the theta and alpha bands (approx. 2-13 Hz) of the unstimulated or near-threshold-stimulated electroencephalogram (EEG). In averages of numerous single trials (20 less than N less than 102), initiated at interstimulus intervals longer than 2.5 sec and deliberately sequenced so that the initiator could learn to estimate the timing of stimulus onsets, the phase coherence of the power-dominant alpha and theta waves within the 100-400 msec time segment of ERBP is obvious when the stimulus is an intense transient and psychologically not "habituated".(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 4019049 TI - Neuropsychological and electrophysiological examination of a patient with Wilson's disease. AB - A patient with Wilson's disease underwent neuropsychological and electrophysiological examination 4 months following symptom onset. Although motor deficits were more severe, there was considerable impairment of cognitive and intellectual function. Auditory evoked responses were also abnormal in this patient. This case is unusual because of the early severe cognitive deficits. PMID- 4019050 TI - Reading disabilities in Japan: evidence against the myth of rarity. AB - The incidence of the reading disabilities among 250 Japanese children (8.5-13.4 years old) was measured by a standardized reading ability test which had recently been developed. It was found that 16.4% of the children tested have a one year delay, and 15.2% of the children have a two year delay. The results show that Makita's (1968) claim concerning the rarity of the incidence of reading disabilities in Japan is incorrect. PMID- 4019051 TI - CNV and time estimation. AB - We investigated the hypothesis that the development and resolution of CNV waves may, in part at least, reflect time estimation processes in the nervous system. Specifically, we postulated that subjects with a high degree of accuracy in time estimation tasks will show a fast resolution of the negativity following the imperative stimulus (S2). The results showed that, consistent with the hypothesis, accurate estimators, as a group, show CNVs with faster resolution of negativity after S2. In addition, they have CNVs of lower amplitude and show a slower rise time to peak negativity than subjects with poor time estimation abilities. PMID- 4019052 TI - Sex and handedness differences in the use of autoerotic fantasy and imagery: a proposed explanation. AB - Previous research has described a greater use of fantasy and imagery during masturbation by men, than women. This study suggests that this gender disparity results from the increased frequency of bilateral speech representation found in the female brain. Support for this theory was obtained by comparing the use of autoerotic fantasy and imagery in another group distinguished by their degree of cerebral lateralization: dextral vs. sinistral males. The prediction that masturbatory fantasy and imagery would be more common in the more lateralized dextral males was partially confirmed in this study. PMID- 4019053 TI - Factor structure and construct validity of the Denman Neuropsychology Memory Scale. AB - Correlational data on the recently published Denman Neuropsychology Memory Scale (DNMS; Denman, 1984) were subjected to a series of factor analyses. Although a major feature of the DNMS is computation of Verbal, Non-Verbal and Full Scale Memory Quotients, the factor analyses did no support this practice. Since the factor results demonstrated initial support for the construct validity of some of the DNMS subtests, it is recommended that interpretation be based on subtest performance. The present results and suggested future investigations of DNMS construct validity are discussed in relation to current issues in clinical memory assessment. PMID- 4019054 TI - Use of background interference procedure to assess visual retention deficits in multiple-sclerosis, psychiatric, and brain-damaged patients. AB - The performances of three groups of patients were compared during two conditions of interference on a visual retention task. During the noninterference condition, the psychiatric, multiple-sclerosis, and brain-damaged patients functioned at a comparable level. The introduction of a distracting background reduced the level of functioning for only the brain-damaged group. This effect remained significant for the correct score when age and postmorbid intelligence functioning were controlled. These results were interpreted as reflecting the cortical nature of the deficits in resisting the distracting influence of the background interference procedure. Serial testing was recommended for the evaluation of the multiple-sclerosis group. PMID- 4019055 TI - Relationships between hand skill and the excitability of motoneurons innervating the postural soleus muscle in human subjects. AB - The relation of hand skill to the excitability of motoneurons innervating the postural soleus muscle was studied in normal human subjects. The motoneuronal excitability was tested by the recovery curve of the Hoffmann reflex. The hand skill was assessed by the peg moving test. Females have been found to be better than males in hand skill. It was established that the H response recovery curve from the right leg was significantly lower than that from the left leg in right handed subjects. The opposite was found in left handers. In ambidexters, there was no significant difference between the heights of the left and right recovery curves. The laterality quotients of the H response recovery curves were normally distributed in the total sample with a mean significantly less than zero, indicating a left shift bais in the motoneuronal excitability. The possible factors contributing to the inverse relationship between hand skill and the excitability of motoneurons innervating the postural soleus muscle were discussed in light of genetic determinants of brainedness and the corticospinal inputs to postural motoneurons. PMID- 4019056 TI - Peak latency differences in evoked potentials elicited by painful dental and cutaneous stimulation. AB - Long-latency evoked potentials (EPs) (50-400 msec) have been obtained from humans during both noxious stimulation of tooth and cutaneous sites in studies of pain and analgesic states. This study investigated whether EPs elicited by tooth and lip stimulation differed in peak latency and whether EPs obtained during painful cutaneous stimulation showed increasing peak latency values with increased conduction distance. Twelve volunteers received painful electrical stimulation at four sites: tooth, lip, thumb, and toe in counterbalanced orders. Evoked potentials recorded at vertex were summation averaged over 128 trials. Multivariate stepwise discriminate analysis was used to determine whether any of the peak latencies of the event-related potentials differed across stimulation sites. No significant latency differences were observed across lip, thumb or toe at any of the major peaks. Since peaks of these EPs did not vary in latency with conduction distance, they appear to reflect processing at higher levels rather than sensory transmission. The negative 140 msec peak of the dental waveform occurred significantly later than the same peak at cutaneous sites. PMID- 4019057 TI - Spatiotemporal changes of EEG activity during waking-sleeping transition period. AB - To evaluate the spatiotemporal changes of EEG during waking-sleeping transition or hypnagogic period, spectral analysis of the five scalp EEG on the midline (Fpz, Fz, Cz, Pz and Oz) referenced to the left ear lobe was carried out on seven young male subjects. Power spectra from consecutive samples of 5.12 sec period with 0.2 Hz resolution were studied from 10 min before the manually scored stage 1 onset to 30 min after the onset of stage 1. The average power spectra over 1 min segments and corresponding coefficient of variation (CV) were determined for the frequency bands of delta (1-3 Hz), theta (4-7 Hz), alpha (8-12 Hz), sigma (13 15 Hz) and beta (16-19 Hz). The latency score was defined as the time elapsed from the onset of stage 1 to the first epoch when the frequency band power, using the ANOVA significantly increased (or decreased) in comparison with the average level at the onset of stage 1. Median latency scores for each band were similar to the Cz scores, with a ranking, from early to late, of: alpha (2 min), theta (3 min), delta (5 min) and sigma (5 min). Significant change was not observed on the beta band activity. In terms of the EEG areas, the shortest latency was found in the theta band activity of the Fz EEG (2 min), and the longest was the sigma band activity of the Fpz and Oz EEG (8 min). The average stage 2 latency was 3.5 min when it was measured as time elapsed between the onset of stage 1 and 2. The average curves of delta, theta and alpha band CVs, started to increase just before or immediately after stage 1 onset and continued to increase for about 10 min. If the increased CV or unsteadiness of EEG activity is taken as a characteristic of the hypnagogic period, hypnagogic states may be considered to have continued until about 10 min after the stage 1 onset. Delta-theta activity showed a rapid rise in power after the onset of stage 1 for all areas. Delta power at the occipital, however, increased more gradually, and consistently remained at a lower level. The differences of delta power between Oz and other four electrode sites became clear at 7 min after the onset of stage 1. These regional differences may reflect the termination of hypnagogic effects.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 4019058 TI - Role of suggestions in digital skin temperature: implications for temperature biofeedback research. AB - The purpose of the present experiment was to explore the role suggestions and assessment procedures play in affecting digital skin temperature. Four different types of suggestions were given subjects (warm, cool, pseudo (electronic terms), and no suggestions). Twenty-five subjects were randomly assigned to the four experimental conditions. The data were analyzed by three popular assessment procedures typically found in the literature. As predicted, subjects displayed significant decreases in skin temperature each day regardless of the training condition they were in. The assessment procedures produced differential results. PMID- 4019059 TI - Interhemispheric transmission: assessment with vibratory somatosensory evoked potentials. AB - Interhemispheric transmission time (ITT) was derived from vibratory somatosensory evoked potentials (VSEP) arising in homologous cortical sensory--association areas of normals. Two different vibratory sources, an audiometer bone oscillator or an Optacon, were used to stimulate each index finger independently. ITT was calculated by subtracting the latency of the first major peak over the contralateral cortex (CL) from the latency of the corresponding peak over the ipsilateral area (IL-CL = ITT). Readily identified aberrant values were observed and rejected from the series of measurements leaving clear normal ranges. In addition to providing normal ITT data, clinical correlations were illustrated in two different disorders. Results suggested that important information relating to diagnosis and therapy of brain pathologies affecting interhemispheric transmission can now be made available in both experimental and clinical situations. PMID- 4019060 TI - Arithmetic model for the distributed encoding in the neuron-module. AB - A class of arithmetic code defined in residue number system (RNS) is proposed as a mathematical model of neural encoding. The formalism of RNS provides for a vectorial representation in which the digits in the code-words (the "coordinates") contain the information in a distributed manner. These digits and the code-words are assumed to represent the states of the neurons and neuron modules, respectively. The involved mechanism appears physiologically possible. After the number-theoretical background is summarized in a brief though self contained way, mathematical assertions are drawn on the error detecting and correction capacities of the formalized modules. It is concluded that RNS provides an appropriate model of neural encoding though drawing inference by the neurons (the evaluation of the encoded information) requires another formalism. PMID- 4019061 TI - Age and education do not affect the Caudality (Ca) Scale of the Minnesota Multiphasic Personality Inventory (MMPI). AB - Age and education effects on the Caudality (Ca) Scale of the Minnesota Multiphasic Personality Inventory (MMPI) were investigated. The MMPI was administered to a sample of 33 lateralized (21 = right hemisphere, 12 = left hemisphere) brain damaged subjects. Demographic data were obtained from hospital records and cross-checked with the subjects. The MMPI profiles were computer scored and Ca Scale t scores were computed. Ca Scale score correlations were computed separately for left and right hemisphere groups for both age and education. All correlations failed to meet conventional standards for statistical significance. Clinical implications are discussed. PMID- 4019062 TI - Sociocultural effects in neuropsychological assessment. AB - The group selected for this evaluation consisted of 109 normal people with an average age of 25, coming from two different sociocultural levels (high and low) of Mexico City. All were completely evaluated by Luria's battery for neuropsychological assessment, adapted by Ardila, Ostrosky, and Canseco, 1981. This group of tests measures nine different areas: Motor Functions, Somatosensory Knowledge, Auditory Knowledge, Visuospatial Knowledge, Cognitive Processes, Language, Reading, Writing and Basic Calculations. For all of these, the higher performance standards were achieved by the subjects from the high sociocultural level. A significant interaction between sociocultural level and sex was observed. The differences between sexes appear only in subjects from the low sociocultural level. Factor analysis of the battery revealed that the most sensitive items to sociocultural level were those related on one hand, to the handling of complex structural and conceptual aspects of language and on the other hand, to the organization of motor sequences and in general motor programming. Research related to the differences found is reviewed and implications for clinical assessment are discussed. PMID- 4019063 TI - Flufenamic acid in prostaglandin migraine. AB - A new class of migraine symptomatology is suggested which consists of major signs of migraine related to disturbances in the menstrual cycle. Not only are these patients different from other migraine patients, they are most responsive to an antiprostaglandin drug. This drug is less useful in other forms of migraine. We suggest that this type of migraine be called prostaglandin migraine. PMID- 4019064 TI - Sleep stages, auditory arousal threshold, and body temperature as predictors of behavior upon awakening. AB - Attempts to demonstrate sleep stage effects on waking behavior have been equivocal at best. The present study provided a more sensitive approach to this problem by assessing performance and subjective alertness at repeated awakenings across baseline sleep and across recovery sleep following 40 and 64 hours of sleep deprivation. These behaviors were then compared to changes in EEG sleep, body temperature, and auditory threshold within these nights. Comparison of means between baseline and recovery sleep indicated that the behavioral variables were generally more sensitive than sleep stages to different amounts of prior wakefulness. Multiple regression analyses revealed no consistent covariation between behavior and any sleep stage which was independent of the correlations among the sleep stages themselves. Thus, distinct functions for specific sleep stages were not apparent from the comparison of means or the regression analyses. However, significant positive covariations were obtained between body temperature and performance, and auditory threshold and sleepiness. Significant negative covariations were obtained between body temperature and sleepiness, and auditory threshold and performance. From these results it was concluded that the most reliable predictors of behavior upon awakening were: the amount of wakefulness prior to sleep, the total amount of accrued sleep, circadian time as indexed by body temperature, and depth of sleep. PMID- 4019065 TI - Impairment in auditory and visual function follows perinatal viral infection in the rat. AB - Acoustic startle reflexes are elicited by intense tone bursts but inhibited if weak bursts precede reflex elicitation. Rats were infected by intracerebral inoculation with lymphocytic choriomeningitis virus (LCMV) at birth. Compared to control animals, infected animals had higher elicitation and inhibition thresholds and showed recruitment at intense stimulus levels. Histopathology revealed both cochlear and retinal degeneration. Like some infectious agents in humans, perinatal exposure to LCMV in the rat yields a severe polysensory neuropathy. PMID- 4019066 TI - Dose effects of halothane on sensory evoked responses obtained from the cortex, reticular formation and central gray. AB - Sensory evoked field potentials were recorded from the mesencephalic reticular formation (MRF), central gray (CG) and somatosensory cortex (SCX), following incremental doses of halothane in freely-moving rats. Halothane concentrations of 0.25%, 0.5% 1.0% and 2.0% were used. In general, the responses from each structure were affected in dose response manner. The averaged acoustic evoked responses (AAER) exhibit more sensitivity to halothane than the averaged visual evoked responses (AVER). The evoked response and its components obtained from each structure were affected differently by halothane mainly following the initial two halothane doses, (0.25% and 0.5%); mainly increase in amplitude was observed in the recording obtained from the MRF, decrease in the CG, and mixed (increase and/or decrease) in SCX. The degree of the depression of the sensory evoked responses was directly correlated to the level of anesthesia as assessed by sural nerve stimulation. PMID- 4019067 TI - Patterns of glycosaminoglycans excretions in the urine of Egyptians differing in their vitamin A status. AB - Fifty-two boys were tested biochemically for their vitamin A status. Only 54% were found to have acceptable Plasma retinol levels. Deficient vitamin A status was associated with reduced GAG excretions. Vitamin A therapy restored the plasma retinol levels and increased the excretion of GAG. Chondroitin sulfate made up 90%, heparan sulfate 9.5% and hyaluronic acid less than 1% of the total urinary GAG content. PMID- 4019068 TI - A simple TLC method for the determination of pro-vitamin A content of fruits and vegetables. AB - A simple and rapid method to isolate and estimate carotene compositions of tomatoes, carrots and green vegetables is described. The chief distinguishing features of this method are its simplicity in the preparation of TLC plates that avoids the requirements of the TLC applicator, and avoiding the meticulous conditions like saturation of chamber etc. employed in the routine TLC methods. By employing this method carotene compositions of tomatoes, carrots and the green vegetable, Amaranthus gangetica are determined. The time taken for the separation of various carotene bands of several samples is as short as 10 minutes. As many as 20 different samples could be analyzed at a time. The values obtained for the individual carotenoids by this TLC method are in very good agreement with those obtained after the column chromatographic separation of the same material. Saponification is not required for the extracts from tomatoes and carrots as it does not influence the individual values of carotenes. Hence in these cases, crude extracts can be directly analyzed by TLC. However, in case of the green vegetables (Amaranthus gangetica, for example) the value of beta-carotene after saponification was found to be twice the value obtained by TLC of the crude extract as such. The general applicability of this method in the separation of vitamin A alcohol from its esters, retinoic acid from retinoic acid anhydride etc. has been discussed. The method would be quite handy and of particular use to especially those carrying out the genetic studies with tomatoes and carrots. It could be employed for a quick and accurate determination of pro-vitamin A content of fruits and vegetables and is more economical than the standard TLC procedures. PMID- 4019069 TI - Stereoisomers of alpha-tocopheryl acetate. III. Simultaneous determination of resorption-gestation and myopathy in rats as a means of evaluating biopotency ratios of all-rac- and RRR-alpha-tocopheryl acetate. AB - The resorption-gestation test furnishes information on a more complex vitamin activity than is the case with other vitamin E tests, so that correspondingly more importance attaches to the results. A drawback is their questionable validity for species other than the small rodents in which fetal resorption has so far been observed. In the four experiments carried out, RRR-alpha-tocopheryl acetate (alpha-TA) was compared with all-rac-alpha-TA (USP standard) and a mean relative activity of 1.32 was determined. The additional measurement of pyruvate kinase (PK) activity serves to emphasize the correlation with nutrition-linked myopathy. This biochemical lesion is seen in various animal species and man. In two experiments, the parameters fetal resorption and plasma PK activity were measured together. For all-rac-alpha-TA and RRR-alpha-TA, the following activity ratios were calculated: Resorption-gestation 1:1.35; Myopathy 1:1.47. It could be shown that the two parameters are measurable quantitatively in a single experimental set-up and that the results are in good agreement. The accepted activity of 1 mg RRR-alpha-TA = 1.36 USP Units was fully confirmed. PMID- 4019070 TI - Tocopherols and tocotrienols in Finnish foods: human milk and infant formulas. AB - Individual tocopherols and tocotrienols in human milk, mother's milk substitutes and other infant formulas have been determined by an HPLC method. 107 human milk samples (23 colostral, 22 transitional and 62 mature) obtained from six healthy mothers throughout the lactation were found to contain all the tocopherols, although delta-tocopherol occurred only in traces. A high content of alpha tocopherol was found in colostrum (average 1.90 +/- 1.62 (SD) mg/100 g), as compared with transitional (0.65 +/- 0.22 mg/100 g) and mature milk (0.47 +/- 0.16 mg/100 g). The content of beta-tocopherol averaged 0.05 +/- 0.03, 0.02 +/- 0.01 and 0.02 +/- 0.01 and gamma-tocopherol 0.11 +/- 0.09, 0.07 +/- 0.04 and 0.07 +/- 0.04 mg/100 g in colostral, transitional and mature milk respectively. The alpha-tocopherol equivalents thus were 1.93, 0.66 and 0.49 mg/100 g; their ratios to the contents of polyunsaturated fatty acids meet the nutritional need of the newborn and young infant: 5.7, 2.1 and 1.4 mg/g in colostral, transitional and mature milk. Mother's milk substitutes and gruel and porridge powders are enriched with tocopherol acetate to vitamin E levels similar to or higher than those in human milk: substitutes contained on average 1.4 mg alpha-tocopherol equivalents/100 g and reconstituted powders 1.1 mg/100 g. The ratio of vitamin E to polyunsaturated fatty acids of these infant formulas was higher than the recommended value of 0.6 mg/g. The average values for alpha-tocopherol equivalents in fruit-berry and meat-vegetable infant formulas were 0.46 and 0.38 mg/100 g. PMID- 4019071 TI - Effect of vitamin E on cholesterol plasma lipoprotein distribution and metabolism in rabbit. AB - In the rabbit, after nine weeks on a basal synthetic diet supplemented with stripped corn oil and varying amount of vitamin E, plasma cholesterol level was depressed as the supplementation of vitamin E was increased. This hypocholesterolemic effect was accompanied by an increase in hepatic cholesterol 7 alpha-hydroxylase activity and cytochrome P-450 level and by a redistribution of plasma lipoprotein-cholesterol resulting in the elevation of high density to low density lipoprotein-cholesterol ratio. PMID- 4019072 TI - Fortification of sorghum beer with thiamin. AB - The consumption of indigenous cereal-based fermented beer is widespread throughout Africa and other parts of the world. In some countries such beer is brewed commercially as well as at home. As evidence of beri-beri may occur in habitual consumers of the beer, the thiamin content of beer brewed commercially from a mixture of sorghum and maize was investigated. Thiamin concentration in beer averaged 0.33 mg/l, with more than 95% in the cellular fraction, mainly live yeast cells. The thiamin in the cells is not generally available for absorption and the cells take up thiamin added to the beer. At low concentrations (0.25-0.5 mg/l) up to 90% of added 14C-thiamin was taken up by the cells but with concentrations in excess of 2.5 mg/l, the uptake was less than 30%. These results indicate that fortification of sorghum beer with thiamin is feasible. The addition of 2.5 mg/l would supply up to 1.6 mg of absorbable thiamin and thus meet the recommended daily allowance in the target group of habitual consumers. PMID- 4019073 TI - Bioavailability of the thiamin administered as an adduct with menadione. AB - In order to investigate the bioavailability of thiamin present in the adduct with menadione bisulfite, urinary and faecalis excretion, blood levels and tissue content of thiamin in rats after oral administration of this compound, were measured. Since the quantity of thiamin excreted, the blood levels as well as the vitamin storage in the liver and kidney of rats treated with the adduct are similar to those of rats treated with corresponding quantities of thiamin HCl and menadione sodium bisulfite this means that the thiamin contained in the adduct reacts in the same way as free vitamin in the animal organism. PMID- 4019074 TI - High performance liquid chromatographic analysis of flavin adenine dinucleotide in whole blood. AB - A method for the determination of Flavin Adenine Dinucleotide in whole blood is presented. The method comprises extraction of the vitamer by using a 6% trichloroacetic acid-20% acetonitrile mixture and direct analysis of the sample extract by using a straight-phase high performance liquid chromatography. A linear calibration curve was obtained for standard vitamer and a satisfactory recovery was observed from spiked samples. Evidence for reproducibility and precision of the assay is presented. The method was applied to determine vitamer levels in blood of healthy subjects. PMID- 4019075 TI - Effect of ascorbic and dehydroascorbic acid on glyoxalase enzyme system. AB - The authors studied the effect of ascorbic and dehydroascorbic acid on glyoxalase enzyme system, in order to establish if these substances influence cell proliferation by interfering with glyoxalase activity. The results demonstrate that both ascorbic and dehydroascorbic acid do not alter glyoxalase activity in vitro, even if employed at high doses. PMID- 4019076 TI - The vitamin status of infants in a free living population. AB - In infancy an adequate intake of vitamins, either from natural sources or as supplements, is of the utmost importance. The vitamin status of 325 infants was studied with regard to their food intake, vitamin supplementation and health from birth to the third birthday. Only data on vitamins A, C, E and folic acid are presented here. The proportion of bottle-fed infants having a serum level of vitamin C less than 0.30 mg/dl was 4.0 times (P less than 0.002), and of vitamin E less than 0.35 mg/dl was 2.2 times (P less than 0.05) higher than that of breast-fed infants. The proportion of infants with folate level less than 6.0 ng/ml was identical in both groups. No infant was observed with a vitamin A serum level less than 40 mcg/dl. The daily food intake of vitamin C less than 80% of RNI was found n 40% of infants at 6 months, in 10% at 12, and in none at 18 months and afterwards. Vitamin A followed a similar trend. 95% of infants had vitamin E and 75% had folate intake less than 80% RNI. Obviously the mean serum levels of vitamins A and C were significantly higher in supplemented infants at 6, 12, 18 and 30 months than in those without supplements. Health indicators, measured by number of self-reported illness related symptoms, differed according to supplementation. These findings indicated that, even if optimal food intake could supply the recommended quantity of vitamins, the risk of marginal deficiency always remained higher in infants without supplementation. PMID- 4019077 TI - [Methionine supplementation in the diet of the pregnant rat. 2. Riboflavin metabolism and hepatic concentration of water, lipid and protein]. AB - Dietary addition of methionine suppresses the liver lipidosis in gestating rat fed a diet containing 9% by weight of casein. Riboflavin metabolism is not affected by this addition neither in the dam nor in the newborn rat. Riboflavin content in liver increases in the dam along with the protein content of the diet but does not change in the newborn rat. PMID- 4019078 TI - Zinc content of the diets of the sedentary Bengalees. AB - The mean values of zinc in seven samples of vegetarian and seven samples of non vegetarian household wholeday diets consumed by sedentary adult Bengalee males belonging to the middle income group were found to be 6.06 mg and 5.33 mg respectively. The average value of all fourteen diets was 5.72 mg. PMID- 4019079 TI - Surgical treatment of portal hypertension in China. AB - In 3,263 cases of portal hypertension, various methods of porta-systemic shunt or portal-azygous disconnection were applied with reasonable results. In addition to the treatment for intractable ascites, peritoneal-jugular shunt and thoracic duct jugular anastomosis were employed in 132 cases. This is our approach to portal hypertension in the big city hospitals. There is much controversy over the suitability of prophylactic surgery and the ideal time for surgery. The reasons for prophylactic surgery and the management of bleeding varices are discussed in this paper. PMID- 4019080 TI - Pneumatic dilatation in the treatment of achalasia. AB - The results of a European survey on pneumatic dilatation in the treatment of achalasia have been compiled from a questionnaire completed by 18 different surgical teams. The total number of patients investigated was 2,161. Surgical treatment was prescribed by 94% of teams, whereas pneumatic dilatation was only prescribed by 56%. The indications for pneumatic dilatation were: inoperability (28%), drug failure (17%), surgical failure (11%). Nine surgeons believe pneumatic dilatation is indicated in all cases (50%), four consider it ineffective and useless (22%), and one expressed no opinion (6%). The arguments in favour of pneumatic dilatation are the fact that the procedure is minor and cost efficient and that it is relatively safe and effective with good long-term results in 75% of cases. Pneumatic dilatation should be used as the initial treatment in achalasia; surgery is only indicated in cases of failure. PMID- 4019081 TI - Surgical techniques for gastroesophagostomy with the EEA stapler. AB - The techniques using the EEA stapler for gastroesophageal anastomoses are described. The instrument saves time, in our opinion, and creates a better anastomosis, which can be inspected under direct vision. No intra- or postoperative complications were noted in this small group of patients. PMID- 4019082 TI - Superinfected actinomycotic abscess of the liver. AB - Isolated actinomycotic liver abscess is rare. We report a case with fulminant evolution, which was treated successfully with surgery and penicillin. In human actinomycosis, Actinomyces israeli is the main infective agent. An abdominal localisation is uncommon, occurring in less than 25% of cases. Isolated liver lesions are extremely rare; their presence might be interpreted as the result of the hematogenous spread of a no longer present intestinal lesion. The evolution of actinomycosis is usually torpid. In the present case, mixed infection with Fusobacterium nucleatum might explain the acute evolution. PMID- 4019083 TI - Reoperation for retained and recurrent bile duct stones. AB - The results obtained in 45 patients who underwent 48 common bile duct reoperations for retained or recurrent choledocholithiasis are reported. The preoperative diagnosis was based on intravenous cholangiography and, in jaundiced patients, on echography and percutaneous transhepatic cholangiography with a Chiba needle. The operations performed on the biliary tract were choledocholithotomy and sphincterotomy (46%), choledocholithotomy (21%), sphincterotomy (16%), choledochoduodenostomy (15%) and Roux-Y choledochojejunostomy (2%). There were three (6.6%) operative deaths: one biliary fistula and two massive digestive hemorrhages. Follow-up lasting from six months to 16 years was carried out in 83% of the patients: 73% reported complete well being. The causes of "secondary" calculosis are analysed with a critical review of the cholangiographic data and the technique performed. The authors conclude that routine operative cholangiography with the possible addition of choledochoscopy, and adequate biliary drainage are sufficient to prevent "secondary" choledocholithiasis. PMID- 4019084 TI - Clinical experience with subxyphoid pericardial decompression. AB - Between 1971 and 1981, 108 patients with pericardial effusion were treated by subxyphoid pericardial decompression. 68 patients (63%) had local anesthesia, while general anesthesia was used in 40 (37%). The total group included nonspecific (viral) pericarditis in 35 patients (32.4%), uremic pericarditis in 30 (27.8%); and 20 patients (18.5%) with a malignant etiology, traumatic in ten patients (9.3%), six patients (5.6%) following radiation for malignant disease, and seven patients (6.5%) due to other causes. Echocardiography was diagnostic in all cases. Acute cardiac tamponade necessitated pericardiocentesis as an initial procedure in seven patients (6.5%). Subxyphoid pericardial decompression included drainage of the pericardial fluid and performance of a 5 X 5 cm pericardial window and biopsy of all patients. There were two (1.8%) operative deaths in the general anesthesia group but none in the local anesthesia group. There were no major complication in the local anesthesia group, but one patient in the general anesthesia group, who was severely hypertensive preoperatively, developed hemiplegia on the left side. There were five recurrences (4.6%) requiring total pericardiectomy at a later date. Subxyphoid pericardial decompression under local anesthesia was seen to be a safe and effective procedure for primary decompression and diagnosis of acute or chronic pericardial effusion. PMID- 4019085 TI - Management of pancreatic pseudocysts in chronic alcoholic pancreatitis with duct dilatation. AB - Twenty-one patients with pancreatic pseudocysts secondary to alcoholic pancreatitis were treated by cystojejunostomy (16), cystoduodenostomy (4) and external drainage (1). In all patients, the duct of Wirsung was drained into a defunctionalized loop of the jejunum at the same operation. There was no early or late mortality. Pseudocyst recurrence did not occur, and only one patient (4.7%) had light pain recurrence in the follow-up period. The importance of providing an outflow route for the obstructed pancreatic duct, and not just for the pseudocyst, is stressed due to this experience with patients affected by underlying chronic pancreatitis. PMID- 4019086 TI - Management of advanced breast cancer in Africa: strategies in the absence of hormone receptor assay data. AB - The oncologist in Africa and many other Third World countries is hampered in the management of breast cancer by the absence of hormone receptor assays in most teaching hospitals. The little information that is available in the literature on hormone receptors in black, breast cancer patients as well as other available hormone receptor information can serve as a data base for the development of a rational approach to this management dilemma. Using the available information, an approach, in the form of a flow chart, has been developed for the management of breast cancer in Africa. It is further suggested that breast cancer should be managed using protocols designed to answer various questions about breast cancer in Africa. PMID- 4019088 TI - Modified Phemister grafting in potentially infected non-union of tibial shaft fractures. AB - Modified Phemister bone grafting consisting of the raising of an osteoperiosteal flap, bone petalling and a cancellous onlay graft for non-union of tibial shaft fractures was tried in 43 cases. Thirty-eight out of 43 fractures united after one bone grafting procedure, giving a success rate of 88%. The procedure can even be used in the presence of low-grade, active infection. This method of bone grafting is simple and has no significant complications. Knee motion recovers well but ankle and toe stiffness do not improve appreciably from the preoperative status. We recommend that Phemister grafting be performed early. PMID- 4019087 TI - Carcinoma of the prostate: the treatment of bone metastases by radioactive phosphorus (32P). AB - The administration of radioactive phosphorus and testosterone benefitted two thirds of thirty patients with prostate cancer treated. Subjective relief of bone pain occurred in 73% of cases and measurable objective improvement occurred in 50%. Hematopoietic depression occurred in 30% of the patients necessitating readmission to hospital for transfusion. This method of treatment is advocated for patients with widespread osseous metastasis, especially those with severe pain. PMID- 4019089 TI - Complete cleft sternum: classification and surgical repair. AB - Primary surgical repair of a complete cleft sternum in a 31-day-old infant is reported. Early surgical repair is recommended because it is usually simple, achieves good results and primary repair is usually feasible. Alternative procedures are discussed and compared with primary repair. The literature is reviewed and a clinical classification of the anomaly is proposed. PMID- 4019090 TI - Cardiac tamponade as the first manifestation of bronchogenic carcinoma. AB - A case of cardiac tamponade as the first manifestation of bronchogenic adenocarcinoma is presented. Diagnosis of metastatic pericarditis with effusion was made by echocardiography and cytology of the pericarditis fluid. Because of rapid recurrence of the effusion, a pericardial window was created. This operation was well tolerated by the patient. A short discussion of metastatic pericarditis is given. PMID- 4019091 TI - Cardiac tamponade and central venous catheter. AB - Two patients survived after emergency surgery for cardiac tamponade which was caused by a central venous catheter perforating the right atrium and the right ventricle. A review of the literature shows 19 reported cases with only two survivals. The possible causes and guidelines for safer use of central venous catheters are discussed. PMID- 4019092 TI - Lipomatosis of the ileocecal valve causing recurrent small bowel obstruction. AB - A case of lipomatosis of the ileocecal valve causing recurrent intestinal obstruction is described. Barium enema with air contrast provides an important diagnostic tool. If confirmed intraoperatively and by histopathologic examination on frozen section, limited resection of the ileum and cecum is advocated rather than blind right hemicolectomy. PMID- 4019093 TI - Multiseptate gallbladder. AB - Nine cases of multiseptate gallbladder have been reported in the English literature. Another case is presented. We consider cholecystectomy the treatment of choice because it relieves the symptoms and avoids chronic infection and stone formation. PMID- 4019094 TI - Transcatheter renal artery embolization in the treatment of infected cutaneous ureterostomy. AB - Palliative renal ablation by means of transcatheter embolization is described. A patient with left cutaneous ureterostomy suffered from urosepsis. The left kidney was embolized using isobutyl-2-cyanoacrylate and Lipiodol in order to stop infected urine excretion. Complete recovery was achieved. PMID- 4019095 TI - Horizontal fusional responses to stimuli containing artificial scotomas. AB - Horizontal fusional responses were studied with stimuli containing binocular or monocular, artificial, stabilized, scotomas. Binocular scotomas of 5-deg, 10-deg, and 15-deg diameters were utilized. The fusional responses to scotomatic stimuli were compared with full-field stimulus responses. All responses contained significant motor and nonmotor (sensory) components. Overall motor compensation to stimuli with 10-deg and 15-deg scotomas was reduced, while the overall motor compensation to stimuli with 5-deg scotomas was not. With full-field stimuli and with stimuli containing binocular scotomas, the changes in the two eyes' lines of sight were often asymmetric in response to symmetric disparity changes. This response asymmetry was exacerbated by the presence of monocular scotomas. Fixation was less steady with stimuli containing 10-deg or 15-deg binocular scotomas than it was in response to full-field stimulation. The fusional responses to annular stimuli were similar to those elicited by scotomatic stimuli. PMID- 4019096 TI - Visual acuity screening of children 6 months to 3 years of age. AB - The operant preferential looking (OPL) procedure allows a behavioral estimate of visual acuity to be obtained from children 6 mo to 3 yr of age. In clinical settings, there is often too little time available to obtain an acuity estimate with the standard OPL procedure. The goal of this study was to identify specific spatial frequencies, termed diagnostic grating frequencies, that could enable the OPL technique to be used as a screening procedure under conditions where completion of acuity estimation was not possible. One hundred eighty presumptively normal children, 6, 12, 18, 24, 30, and 36 mo of age, were each tested with up to 20 trials of a potential diagnostic grating frequency to determine the highest spatial frequency grating that could be resolved by 90% of children at each age. For all ages except 18 mo, there existed a spatial frequency that produced uniformly high OPL performance within the age group; this spatial frequency was separated by one-half to one octave from a higher spatial frequency that more than 30% of children at that age failed to detect. These results suggest that at all ages except 18 mo, it should be possible to use the OPL procedure as a vision screening tool by testing individual children with the diagnostic grating frequency appropriate for their age. PMID- 4019097 TI - Pupillary measures of binocular luminance summation in infants and stereoblind adults. AB - Preverbal infants and children with ocular misalignments do not perform well on standard clinical measures of binocular function which require accurate alignment of the eyes. In 1983, Birch and Held described a pupillary measure of binocular luminance summation that could be used to assess binocular function in strabismic infants. They reported a correlation between the onset age of stereopsis and the onset age of binocular luminance summation, with both emerging at the end of the fourth postnatal month. Using a similar pupillary technique, we measured significant levels of binocular luminance summation in infants as young as 2 mo of age, as well as in stereoblind adults. In addition, the infant's pupillary system, in comparison to the adult's, showed reduced magnitudes and increased latencies to luminance increments. The sensitivity of the pupillary system to luminance increments provided a better predictor of binocular luminance summation (Pearson r = 0.88) than did stereoscopic performance (Pearson r = 0.43). These data suggest that developmental changes in the pupillary system itself, rather than factors intrinsic to binocular vision, may have been the source of the correlation between binocular luminance summation and stereopsis reported by Birch and Held. PMID- 4019098 TI - Visual evoked potentials in macular disease. AB - Although a delayed visual evoked potential is considered to be the hallmark of optic nerve disease, relatively little has been published about VEP delays in macular disease. In this study, 20 patients with either acquired unilateral maculopathy or bilateral maculopathy in which one eye was more affected than the other were evaluated. VEP amplitudes and peak latencies were compared between eyes when recordable. Nine patients (45%) exhibited significant interocular delays in the affected or more affected eye while only four patients (20%) exhibited significant interocular attenuations in amplitude. In the nine patients exhibiting delays, three patients had a visual acuity of 20/30 or better in the affected eye or more affected eye. In the patients exhibiting amplitude attenuations, no patient had a visual acuity better than 20/50 in the affected or more affected eye. Although the mechanism of VEP delays in maculopathy is not clear, a VEP delay, in isolation of other tests, should not be used in the differential diagnosis of macular vs optic nerve disease. The clinician should specifically rule out macular disease in any patient with a delayed VEP before presuming the presence of a visual pathway dysfunction. PMID- 4019099 TI - Biochemical features of the grey squirrel lens. AB - The ocular lens of the grey squirrel (Sciurus carolinensis) is an excellent model for studies of eye-light interactions that apply to the human system. In this diurnal animal, lens size, shape, yellow pigmentation, and light absorption properties have important similarities to those of young children. This article describes the observations of soluble to insoluble protein conversion with chronological aging, and the loss of heavier lens crystallins in the internal as compared to the external layers of the lens. Such changes are related to aging, as the older lens material is present in the nuclear core, while the younger lens material is superficial. It describes the subunit peptides of the soluble crystallins and of the extrinsic and instrinsic proteins associated with fiber cell membranes. Squirrel lens fiber membranes release most of their extrinsic peptides in 8 M urea, as do those of other young animals. Due to the presence of near-UV absorbing species of low molecular weight, the squirrel lens has great potential for studies of the effects of near-UV radiation on the lens. PMID- 4019100 TI - The neurologic evaluation of patients with low-tension glaucoma. AB - One hypothesized cause of low-tension glaucoma is chronic or intermittent ischemia of the optic nerve. Since the optic nerve and brain are both parts of the central nervous system and share a common blood supply, the authors wondered if patients with low-tension glaucoma might also have clinical or radiographic evidence of cerebral atrophy. In this study, 27 patients with low-tension glaucoma were examined using neurobehavioral testing, electroencephalography, computerized tomographic scan, neurological history, and physical examination. In only a small number of patients were these tests abnormal. However, 12 of the 27 patients gave a history of common or classic migraine. This unexpected finding raises the possibility that migraine-related ischemia might be the pathogenic mechanism in some cases of low-tension glaucoma. PMID- 4019101 TI - Migraine and low-tension glaucoma. A case-control study. AB - The authors administered a standardized headache questionnaire to 54 patients with low-tension glaucoma, 182 patients with primary open-angle glaucoma, 126 patients with ocular hypertension, and 493 normal subjects. Patients with low tension glaucoma had headaches with or without features of migraine (unilateral headache, nausea or vomiting, or visual prodromata) more frequently than did any of the other groups. The higher prevalence of headache in low-tension glaucoma patients, who were usually elderly, was especially striking when their age was considered, since headaches are less common in elderly normal subjects than in young normal subjects. Headaches were present in 86% of elderly low-tension glaucoma patients (70 yr of age or older) but in only 64% of elderly normal subjects (P = 0.04) and only 59% of elderly ocular hypertensive patients (P = 0.02). Because migraine is an ischemic disorder, its possible association with low-tension glaucoma has etiologic and therapeutic implications. PMID- 4019102 TI - Destruction of the indoleamine-accumulating amacrine cells alters the ERG of rabbits. AB - The indoleamine-accumulating amacrine cells in the rabbit's retina were destroyed by intravitreal injections of 5,7-DHT according to the technique of Ehinger and Floren. One week after the injections, histofluoresence microscopy failed to show the IA-cells in the retina. At this time, the b-wave of the treated eyes was significantly smaller, the OPs were more prominent, and the duration of the b wave was longer. The a- and c-waves and the off-response were not affected. The loss of the IA-cells resulted in a reduction in the range of dark-adaptation but did not affect the rate of recovery of the threshold. The loss of the IA-cells also had no effect on the response of the retina to flickering light. In a double flash experiment, the suppression of the response to the second flash was significantly weaker in the treated eyes. These results can be explained by the loss of a negative feedback circuit that has been proposed for the IA-cells from morphologic studies. PMID- 4019103 TI - Blood velocity and volumetric flow rate in human retinal vessels. AB - The distributions of blood velocity and volumetric flow rate in individual vessels of the normal human retina were determined as a function of vessel diameter. The mean velocity of blood, Vmean, was calculated from the centerline velocity measured by bidirectional laser Doppler velocimetry (LDV). Volumetric flow rate was determined from Vmean and the vessel diameter, D, measured from monochromatic fundus photographs. Diameter of the arteries and veins at the site of the LDV measurements ranged from 39 to 134 microns and 64 to 177 microns, respectively. Flow velocity correlated with D (P less than 0.001 for both arteries and veins). Volumetric flow rate varied with D at a power of 2.76 +/- 0.16 for arteries and 2.84 +/- 0.12 for veins, in close agreement with Murray's law. Calculated from 12 eyes, the average total arterial and venous volumetric flow rates were 33 +/- 9.6 and 34 +/- 6.3 microliters/min, respectively. The good agreement between both flow rates suggests that the technique and the assumptions for calculating flow yield results that satisfy mass conservation. Total arterial and venous volumetric flow rates correlated with total arterial and venous vessel cross-section. Volumetric flow rate in the temporal retina was significantly greater than in the nasal retina, but the difference is likely to be due to the larger area of the temporal retina. No difference in flow rate was observed between the superior and inferior retinal hemispheres. Finally, blood velocity in the major retinal vessels measured under normal experimental conditions appears remarkably constant over short (hours) and long (months) periods of time. PMID- 4019104 TI - The effect of pH on the transfer of fluorescein across the blood-retinal barrier. AB - The blood-retinal barrier (BRB) might be governed by the same permeability principles as the blood-brain barrier (BBB). For a weak acid like fluorescein, BRB permeability would be proportional to its pH-dependent lipid solubility, according to the pH partition hypothesis. A range of metabolic acidosis was produced in 20 rats by the oral administration of NH4Cl; six additional rats received normal saline. Four hours later, vitreous fluorophotometry, venous fluorescein values, and arterial pH were measured. Significant linear relationships were found between vitreous fluorophotometry readings and blood hydrogen ion concentrations (p less than 0.025) and plasma fluorescein concentrations (p less than 0.05). According to the linear relationship, changing the pH from 7.4 to 7.3 or 6.9 would result in an increase in vitreous fluorophotometry reading of 8.5 or 72%, respectively. Since the pH partition hypothesis predicts values of 52 or 640% our results suggest that the BRB conforms less to the hypothesis than does the BBB. Furthermore, although pH changes of a magnitude able to influence vitreous fluorophotometry readings substantially may occur under experimental conditions in animals, they are unlikely to occur in ambulatory human patients. PMID- 4019105 TI - A comparison of lipid metabolism in two human retinoblastoma cell lines. AB - A number of differences have been observed in the lipid metabolism of cultured Y79 and WERI Rb-1 retinoblastoma cells. The Y79 cells have a higher phospholipid content and a higher percentage of ethanolamine phosphoglycerides, whereas the WERI Rb-1 cells have more triglycerides. This is consistent with the finding that most of the polyunsaturated fatty acid taken up by the Y79 cells is incorporated into phospholipids, while a sizable amount of the uptake in WERI Rb-1 cells is incorporated into triglyceride. Polyunsaturated fatty acids of the n-6 class are taken up at about the same rate by both cells, but the n-3 polyunsaturates are taken up more rapidly by the Y79 cells. In addition, the Y79 cells convert a larger percentage of linoleic acid (18:2, n-6) to arachidonic acid (20:4, n-6) and of linolenic acid (18:3, n-3) to docosahexaenoic acid (22:6, n-3), and they accumulate these products when the precursors are added to the culture medium. When grown in 10% fetal bovine serum without supplemental fatty acid, however, the WERI Rb-1 contain more arachidonic and docosahexaenoic acids. These differences in lipid content and metabolism suggest that although the Y79 and WERI Rb-1 cell lines are derived from the same type of retinal tumor, they either originated from functionally different retinal neurons or have diverged biochemically during propagation in culture. PMID- 4019106 TI - The use of hyperbaric oxygen therapy in the treatment of sickle cell hyphema. AB - Eyes of adult albino rabbits were injected intracamerally with either normal saline or anticoagulated human sickle cell blood to study the effect of hyperbaric oxygen administration on sickle cell hyphema. The administration of two atmospheres of 100% oxygen for 2 hr to the rabbits raised the pO2 of the aqueous humor from a baseline value of 63.5 +/- 12.3 mmHg (mean +/- SD) to 620 +/ 133 mmHg in saline-injected eyes and 503.7 +/- 89.1 mmHg in eyes injected with human sickle cell blood. This rise in pO2 was highly significant (P less than 0.0001). The percentage of sickled cells in the anterior chamber 2 hr after injection decreased from 35.7 +/- 32.4% in rabbits breathing room air to 4.1 +/- 2.8% in rabbits exposed to hyperbaric oxygen for 2 hr. Hyperbaric oxygen can thus significantly raise aqueous humor pO2 values and decrease the sickling of erythrocytes in the anterior chamber and may be of value in patients with sickle cell hyphema. PMID- 4019107 TI - The acuity card procedure: a rapid test of infant acuity. AB - Forced-choice preferential looking (FPL) and operant preferential looking (OPL) procedures for testing infant acuity typically require 15-45 min to derive an acuity estimate. This article presents a new acuity assessment technique ("acuity cards") that combines FPL/OPL stimuli with an observer's subjective assessment of an infant's looking behavior. The infant is shown a series of gray cards that contain grating targets of various spatial frequencies. An observer watches the eye movement patterns and behavior of the infant and judges whether the infant can or cannot see the grating on each card in the series. Acuity is estimated as the highest spatial frequency that the observer judges the infant to be able to see. With this technique, the binocular acuity of normal infants can be estimated with reasonable accuracy in the laboratory setting in 3-5 min. PMID- 4019108 TI - Age dependence of freezable and nonfreezable water content of normal human lenses. AB - The cortex, intermediate zone, and nucleus of 19 normal human lenses between the ages of 3 and 77 yr were investigated. The freezable water content of the lenses was obtained by differential scanning calorimetry. The total water content was measured by vacuum dehydration. The nonfreezable water content was calculated from these two measurements. The total water content of the nucleus and intermediate layers decrease with age, while that of the cortex does not vary appreciably. The nonfreezable water content of all three regions of normal human lenses decreases with age. PMID- 4019109 TI - Role of the crystalline lens in the spatial vision loss of the elderly. AB - This study examined the contribution of the crystalline lens to the spatial contrast sensitivity loss experienced by many healthy older adults. Spatial contrast sensitivity was measured in three groups of adults: older adults who had undergone cataract extraction and intraocular lens (IOL) insertion; older adults who were in good ocular health (agematched to the first group); and young adults also in good ocular health. Older adults had decreased contrast sensitivity at higher spatial frequencies compared to young adults, agreeing with earlier reports. In addition, both groups of older adults had similar contrast sensitivity at higher frequencies, contrary to what would be expected if the aged, noncataractous crystalline lens significantly hampered contrast transfer in the healthy older eye. Results imply that the crystalline lens is not primarily responsible for the spatial sensitivity loss of healthy older adults. Furthermore, these data indicate that for at least some IOL patients, spatial vision can be restored to a level similar to their agemates who have no history of lens opacity or ocular disease. PMID- 4019110 TI - Gender-related differences in the morphology of the lacrimal gland. AB - Previous research has demonstrated that distinct, gender-related differences exist in the morphology of the rat lacrimal gland. The purpose of the present study was to determine whether this sexual dimorphism is unique to the rat, or extends as well to other species. Lacrimal glands were collected from adult male and female rats, mice, guinea pigs, rabbits and humans (biopsies). Tissues were processed for light microscopy and examined with a Zeiss Videoplan II image analysis system. For morphometric determinations, we measured the area of approximately 50 glandular acini per animal for a total count of greater than 244 acini per gender per species. Our results demonstrated that significant gender related differences exist in lacrimal glands of rats, mice, guinea pigs, rabbits, and humans. In all species analyzed, acinar area in lacrimal glands of males was larger than that of females. These findings suggest that gender differences in lacrimal gland morphology may be a general phenomenon in a variety of species. PMID- 4019111 TI - Binding of fluorescein monoglucuronide to human serum albumin. AB - The binding to human albumin of fluorescein monoglucuronide, a fluorescent metabolite of fluorescein, was studied using two methods: pressure dialysis and fluorescence polarization. Both methods indicated that fluorescein monoglucuronide binds to human albumin more loosely than fluorescein. The free fraction in human plasma estimated from the dissociation constant and the number of binding sites was in a range from 31 to 37%. Fluorescence of fluorescein was significantly quenched by the albumin binding, but fluorescence of fluorescein monoglucuronide was not affected by albumin. The relative molar intensity of fluorescence between these fluorophores varied from 3.2 to 37.3, depending on the excitation wavelength. PMID- 4019112 TI - Prostaglandins E3 and D3 lower intraocular pressure. AB - The effects of the prostaglandin (PG)-3 series products PGE3 and PGD3 on the intraocular pressure of rabbits were studied. PGE3 at 0.001 and 0.01 mg/eye and PGD3 at 0.01 and 0.05 mg/eye doses were applied topically (in 50-microliters volume) to the normal rabbit eye. Both PGE3 and PGD3 significantly lowered intraocular pressure at all doses tested and the IOP lowering response lasted at least 240 min. Topical PGE3 at 0.01 mg/eye caused mild conjunctival hyperemia which lasted up to 180 min. PGD3, on the other hand, did not induce conjunctival hyperemia. In addition, following application of these PGs, there was no miosis or other sign of intraocular inflammation detectable by slit-lamp examination. PMID- 4019113 TI - Statistical analysis of multi-eye data in ophthalmic research. AB - An apparently common error in statistical analysis of ophthalmic data is to perform statistical tests that do not account for the correlation generally present between observations made for the right and left eyes of a subject. This error has as a consequence an overstatement of the precision of the study, resulting in incorrect P values which indicate a greater measure of statistical significance than the data warrant. As measures to reduce the occurrence of this serious error in statistical analyses, the authors recommend increased emphasis on educational programs for investigators, stimulation of nontechnical articles reviewing statistical methods, and a sharper focus upon statistical analysis in the peer review process. PMID- 4019114 TI - Improved method for restraining rabbits for examination of the eye. PMID- 4019115 TI - The pharmacokinetics and metabolism of mitoxantrone in man. AB - An HPLC method using paired-ion chromatography on RP C-18 material was developed. After sample clean up on XAD columns, mitoxantrone (Novantrone; dihydroxyanthracenedione) in concentrations below 1 ng/ml in serum and 0.2 ng/ml in urine were measurable with a coefficient of variation less than 9.3% at a wavelength of 658 nm. Four metabolites were separated in urine. The major metabolite cochromatographed with the synthesized dicarboxylic acid of mitoxantrone. Within 48 hours 4.4% of the administered dose was excreted in urine as mitoxantrone, 0.5% as metabolite 1 and 0.3% as metabolite 2. The pharmacokinetic parameters are adequately described by a three-compartment model with a terminal half-life of 214.8 hours, and a volume of distribution (ss) of 3792 litres. The total body clearance was 358 ml/min and the renal clearance was 26.2 ml/min. PMID- 4019116 TI - Evaluation of mitoxantrone cardiac toxicity by nuclear angiography and endomyocardial biopsy: an update. AB - Sixty-six patients who underwent endomyocardial biopsy for detection of mitoxantrone (Novantrone; dihydroxyanthracenedione) cardiac toxicity were evaluated. All but one had breast cancer, 29 had received prior doxorubicin and 29 of the 37 patients who had not had prior doxorubicin received it or another anthracycline subsequently. Endomyocardial biopsy was carried out initially after four courses of chemotherapy with increasing intervals thereafter. Although cardiac ejection fraction was determined before each course of chemotherapy, our data are limited to cardiac ejection fractions from our own institution which were repeated approximately every four courses. Endomyocardial biopsy changes consisting of dilatation of the sarcoplasmic reticulum with vacuole formation, and myofibrillar dropout are similar to the early changes of anthracycline cardiomyopathy. While there was a slight suggestion of increasing biopsy grade with increasing mitoxantrone dose, no significant changes in cardiac ejection fraction could be associated, regardless of prior doxorubicin therapy. We concluded that mitoxantrone does show morphologic evidence of cardiac toxicity; however, the structural changes are minor and are haemodynamically insignificant. Determination of how much mitoxantrone treatment may contribute to the deterioration of pre-existing doxorubicin damage must await the outcome of longer follow-up. PMID- 4019117 TI - Mitoxantrone as a first-line treatment of advanced breast cancer. AB - Forty-two women with measurable or evaluable advanced breast cancer who had received neither prior chemotherapy for advanced disease nor any anthracycline containing regimen as adjuvant were entered in a phase II study of mitoxantrone (Novantrone; dihydroxyanthracenedione). Patients were aged from 36 to 80 years, performance status was from 0 to 2. All patients had normal hematological status and normal renal and liver function tests. Cardiac scintigraphy and sonography techniques were used to monitor cardiac function. Mitoxantrone was administered at a dose of 14 mg/m2 in 100 ml 5% dextrose solution over 30 minutes, repeated every three weeks. The number of courses per patient ranged from 2 to 12. Of 42 eligible patients 39 were fully evaluable for response and all for drug toxicity. Responses to treatment were: complete response four patients, partial response 10 patients, stable disease 18 patients and progressive disease seven patients. The overall response rate was 36% (95% confidence limits 20-52%). Three patients showed decreased left ventricular ejection fraction but no patient developed signs of overt left ventricular failure during the treatment period. Hematological and gastrointestinal toxicities were mild. Hair loss was minimal. The data indicate that mitoxantrone is an effective agent for the treatment of advanced breast cancer with mild side-effects, especially with respect to nausea/vomiting, hair loss and cardiotoxicity. PMID- 4019118 TI - Mitoxantrone as first-line chemotherapy in advanced breast cancer: results of a collaborative European study. AB - Mitoxantrone (Novantrone; dihydroxyanthracenedione) is a substituted anthraquinone with a spectrum of activity similar to doxorubicin in experimental tumors. One hundred and seventy three patients with advanced breast cancer and no prior cytotoxic therapy for advanced disease entered a phase II study of mitoxantrone, 14 mg/m2 i.v. repeated every 3 weeks. At the time of this analysis 116 patients were evaluable. Eight patients achieved a complete response and 27 a partial response, the overall response rate being 30% (95% confidence limits: 22 39%). The median time until response was recorded was 15 weeks. The median duration of response was 74+ weeks and the median time to progression or death for all 116 patients was 22+ weeks. Mitoxantrone was well tolerated with myelosuppression as the dose-limiting toxicity. The most frequent non haematological toxicities were nausea and vomiting (65%) but they were rarely severe. Total alopecia occurred in only 6% of the patients. Four patients developed clinically significant evidence of cardiotoxicity after cumulative mitoxantrone doses of 174-256 mg/m2. Thus, mitoxantrone offers comparable efficacy and less acute toxicity than the most active single agents currently available in the treatment of advanced breast cancer. PMID- 4019119 TI - Mitoxantrone combined to vincristine, cyclophosphamide and fluorouracil in advanced breast cancer. AB - In our wide experience of treating advanced breast carcinoma with chemotherapy, the combination of doxorubicin (DOX), vincristine (VCR), cyclophosphamide (CPM) and fluorouracil (FU) gave a complete plus partial response rate of over 60%, with 100% alopecia and frequent cardiac toxicity depending on total dose. After the EORTC Clinical Screening Group phase II trial we have conducted an "expected difference method" comparative phase II trial using the combination DOX, VCR, CPM, FU and the combination of MTX (10mg/m2), VCR, CPM and FU on a population of 50 breast carcinoma patients similar to those taking part in the first study. The reasons for similarity of action will be presented and discussed. PMID- 4019120 TI - First-line combination chemotherapy with mitoxantrone and cyclophosphamide in advanced breast cancer. AB - In this study, 30 evaluable patients with advanced carcinoma of the breast were treated with cyclophosphamide 600 mg/m2 i.v. followed one day later with mitoxantrone (Novantrone; dihydroxyanthracenedione) 16 mg/m2 i.v. Drug treatment was repeated every 3-4 weeks, for a maximum of 12 cycles. The overall response rate was 43%; five of 30 patients (16%) attained a complete remission, and eight of 30 (27%) had a partial remission. Median response duration was 12+ months. The greater number of responses was seen in skin and soft tissues. Hematologic toxicity was limiting with 75% of patients experiencing substantial-severe leukopenia. Clinically evident heart failure developed in one patient; in three other patients there was minor-moderate alteration of cardiac function during mitoxantrone-cyclophosphamide therapy. Based on these data, it is believed that this regimen may provide significant long-lasting palliation in patients with advanced breast cancer. PMID- 4019121 TI - Phase II studies of mitoxantrone in patients with primary liver cancer. AB - Forty-nine patients with histologically confirmed primary liver cancer have been entered on phase II trials of mitoxantrone (Novantrone; dihydroxyanthracenedione), at a dose of 14 mg/m2 every 3 weeks. Among the patients evaluable for toxicity, leukopenia and thrombocytopenia were the most important side-effects encountered. Partial responses have been observed. In a significant number of patients the disease remained stable for at least 1 month. At present the median survival time is, however, only 12 weeks. The response rate and median survival times are similar to those documented with other single cytotoxic drugs, given to comparable groups of patients with primary liver cancer. PMID- 4019122 TI - Mitoxantrone in refractory acute leukemia in children: a phase I study. AB - Nine children with acute non-lymphocytic leukemia (ANLL), ages 16 months to 16 years (median 7 years), and 15 children with acute lymphocytic leukemia (ALL), ages 10 months to 18 years (median 5 years), were treated with 5-day courses of mitoxantrone (Novantrone; dihydroxyanthracenedione) as induction therapy. All the children had leukemia which was resistant to conventional therapy and all but one patient had received anthracycline therapy prior to the initiation of this trial. Three patients (two with ANLL, one with ALL) received the drug at a dose of 6 mg/m2/day i.v. for 5 days. Both patients with ANLL achieved partial remissions (PR) (105 and 87 days duration). The child with ALL failed to respond to two courses of the drug, and died of progressive disease 45 days after the institution of therapy. Twenty-one patients (14 with ALL, seven with ANLL) were treated with 8 mg/m2/day i.v. mitoxantrone for 5 days. There were three early deaths (all ALL) which were not felt to be secondary to drug toxicity. Four of the 18 children achieved complete remission (CR) (one ANLL - 35 days; three ALL - 39, 31 and 13 days). One child with ANLL achieved a PR (13 days) and one child with ALL showed improvement in his bone marrow status. Twelve children failed to respond to this therapy. Dose-limiting toxicity was not seen among the patients who received 6 mg/m2/day for 5 days. There were five patients who had mucositis and one patient who had nausea and vomiting among those patients who received 8 mg/m2/day for 5 days.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4019124 TI - Increased platelet aggregation following splenectomy in patients with myeloproliferative disease. AB - In 30 patients with myeloproliferative disorders, decreased platelet aggregation in response to both ADP and collagen was demonstrated. The hypoaggregability was more drastic in patients with large spleens. Patients who had had splenectomy in the past showed normal platelet aggregation. In order to understand the role of the spleen in platelet function, platelet aggregation was studied in three patients with myeloproliferative disorders during the week following splenectomy and was compared to platelet aggregation in three control patients undergoing orthopedic operations. After splenectomy, platelet aggregation significantly increased, reaching a maximum after 3 to 4 days, but returned to presplenectomy values after 1 week. This is in contrast to the control patients, in whom no significant changes in platelet aggregation were observed. Our results suggest that the spleen retains or catabolizes the most hemostatically effective platelets. PMID- 4019123 TI - Mitoxantrone in malignant lymphoma. AB - Two phase II trials of mitoxantrone (Novantrone; dihydroxyanthracenedione) in refractory malignant lymphoma have been conducted. In the first of these, mitoxantrone, 5 mg/m2, was given weekly for six weeks and in the second, 14 mg/m2 was administered every three weeks. The first trial was conducted by the Southeastern Cancer Study Group (SECSG) and the second was a multicenter trial sponsored by Lederle Laboratories. Of the 51 patients entered in the SECSG trial, 28 could be evaluated for response and 43 for toxicity. WBC nadirs below 4.0 X 10(9)/litre were recorded in 25 patients. Three partial responses and no complete responses were obtained. These results contrast with those of the single dose every three weeks study in which 96 patients were entered and 69 of these were evaluated for response. Responses were obtained in 30 patients (4 complete, 26 partial). Side-effects on this three-weekly dose regimen were minimal. WBC nadirs below 4.0 X 10(9)/litre occurred in 85 patients. Twenty-three patients experienced at least mild nausea and vomiting and 15 had at least mild alopecia. These preliminary data indicate that mitoxantrone has significant activity in malignant lymphoma. All of the responding patients had received extensive prior therapy, many of them with anthracyclines in combination or as single agents. The higher response rate to mitoxantrone given at 14 mg/m2 every three weeks suggests that careful consideration should be given to dose schedule when this drug is examined further in phase III trials. PMID- 4019125 TI - Unexplained episodes of fever: an early manifestation of colorectal carcinoma. AB - The possibility that fever may be an early manifestation of colorectal carcinoma was examined. Of 92 consecutive patients, 28 had preoperative fever. In four patients the fever was the presenting symptom of the colonic tumor, and in another six patients it preceded gastrointestinal complaints by 1 week to 4 months. Fever was thus the earliest manifestation of colorectal carcinoma in 10.8% of the patients. In 13 of the 28 patients the fever could not be explained by the intraoperative findings. We suggest that transient bacteremia may be a common but frequently overlooked manifestation of colonic cancer. Prognosis of the patient may be improved by alertness to the possibility that an episode of unexplained fever may be the first, and sometimes the only, manifestation of colorectal carcinoma. PMID- 4019126 TI - In vitro synthesis of IgE in atopic and nonatopic individuals: the effects of pokeweed mitogen, Staphylococcus aureus-derived mitogens, and cycloheximide. AB - We studied the production of immunoglobulin (Ig)E in cultures containing mononuclear cells obtained from atopic and nonatopic subjects. The two groups did not differ in their baseline production of IgE. Pokeweed mitogen (PWM) and three different products of Staphylococcus aureus: purified protein A, heat-killed formalinized bacteria, and double-formalinized bacteria--induced a significant increase in the in vitro production of IgE. Mononuclear cells from both atopic and nonatopic individuals were stimulated to the same degree by all four mitogens. The increased production of IgE by PWM was totally abolished by cycloheximide; hence it was due to de novo protein synthesis. PMID- 4019127 TI - Carotid sinus syndrome: an overlooked cause of syncope. AB - Carotid sinus syncope was diagnosed during a 2-year period in 21 men and 5 women, aged 51 to 80 years, who had experienced 1 to 30 syncopal episodes during periods of time which varied from 1 day to 6 years. In 19 of these patients there was evidence of organic heart disease. Carotid sinus hypersensitivity of the cardioinhibitory type was present in 14 patients, the vasodepressor type in 1 patient, and a mixed type in 7 patients. In four patients with the cardioinhibitory response, the possibility of the vasodepressor response was not excluded. A pacemaker was placed in 17 patients, deferred in 4 patients and refused by 5 patients. Follow-up of patients with pacemakers over 9.5 +/- 7.0 (SD) months revealed recurrence of symptoms in two patients due to a previously unrecognized vasodepressor response. Follow-up of the patients without pacemakers was brief (4.6 +/- 3.7 months), and they remained asymptomatic, except for one patient with recurring vertigo. PMID- 4019128 TI - Septicemia with two distinct strains of Staphylococcus aureus and dwarf variants of both. AB - A patient with erythema multiforme developed septicemia with two strains of Staphylococcus aureus. Six blood cultures, obtained during 14 days, yielded a mixture of both strains. The strains differed in the ability to hemolyze human erythrocytes, in the production of beta-lactamase and in the susceptibility to antibiotics and bacteriophages. Following therapy with gentamicin, a Dwarf colony variant auxotrophic for vitamin K, tryptophan and p-aminobenzoic acid appeared in some of the blood cultures. This variant was apparently derived from one of the offending strains (phage Type 55/71). From other blood cultures, a different type of Dwarf colony variant was obtained; this variant was of the same phage type as the other offending S. aureus strain (Type 85). The metabolic deficiencies of this strain were not unraveled. Both events, the double infection with distinct S. aureus strains, and the emergence of Dwarf variants during antibiotic therapy, are unusual in clinical practice, and will be detected only if laboratory staff pays particular attention to the possible occurrence of such events. PMID- 4019129 TI - Temporal lobe meningioma masked by polymyalgia rheumatica. AB - An elderly woman who had a typical polymyalgia rheumatica (PMR) syndrome, associated with severe headache, was considered to have giant cell arteritis despite negative temporal artery biopsies and was treated with corticosteroids. At autopsy, no arteritis, but a large temporal lobe meningioma, was found as the cause of her headache. Both PMR and meningiomas are frequent in elderly patients, and overlapping symptoms may occur. Patients with PMR and headache should be fully investigated to exclude an occult meningioma or other disease, especially when no positive histologic evidence of temporal arteritis can be obtained. PMID- 4019130 TI - Rheumatic carditis presenting as acute myocardial infarction. AB - Two weeks following streptococcal tonsillitis two patients developed migratory arthralgia, fever and pericarditic chest pain, followed by an episode of severe coronary retrosternal pressure. The ECG during the latter episodes revealed ST elevation in the inferior wall leads, followed later by the appearance of pathological Q waves in the same leads which persisted for only a few days. Radionuclide scans and echocardiographic studies revealed localized involvement of the inferior left ventricle in both cases and, in addition, involvement of the right ventricle in have been suggested to explain the co-occurrence of viral myopericarditis and myocardial infarction (MI)-like picture during acute rheumatic fever can be explained either by coronary vasculitis resulting in myocardial ischemia, or by direct involvement of the myocardium because of an inflammatory process. Both mechanisms have been suggested to explain the co occurrence of viral myopericarditis and myocardial necrosis. The transient Q waves were probably produced by stunning of the myocytes during the acute phase of the disease. Increased awareness will probably result in detection of similar cases and may contribute to understanding the pathogenesis of the MI-like picture of acute rheumatic fever. PMID- 4019131 TI - Plasma fibronectin levels in various clinical conditions. PMID- 4019132 TI - Newborn with multiple joint contractures due to maternal bicornuate uterus. PMID- 4019133 TI - Cutaneous leishmaniasis due to Leishmania braziliensis in an Israeli tourist. The importance of accurate diagnosis and appropriate therapy. PMID- 4019134 TI - Sternoclavicular arthritis and osteomyelitis due to Pseudomonas aeruginosa, not related to drug abuse. PMID- 4019135 TI - Salivary composition in asthmatic children on theophylline. PMID- 4019136 TI - Salivary theophylline: a reliable alternative to monitoring serum levels? PMID- 4019137 TI - Rapid growth of human epithelium in tissue culture. PMID- 4019138 TI - Perianal tuberculosis, a case report. PMID- 4019139 TI - Hyperchloremic acidosis during the recovery phase from diabetic ketoacidosis. PMID- 4019140 TI - Chorion villi biopsy. PMID- 4019141 TI - Screening for neonatal hypothyroidism in Israel during a 4-year period. AB - The neonatal hypothyroidism (NH) screening program in Israel was initiated in May 1978, and by the end of April 1984, 538,565 infants had been screened. One hundred sixty-six newborns were found to have NH; 7 of these exhibited only transient hypothyroidism. During the screening period the average age for initiation of treatment decreased from 6 to 4.8 weeks. A thyroid scan was performed on 51 of the neonates with NH; 41% had agenesis of the thyroid, 24% ectopic thyroid tissue, 29% dyshormonogenesis, and 6% secondary or tertiary hypothyroidism. This high incidence of dyshormonogenesis in Israel is probably due to a high rate of consanguinity among the Arab population and also within some of the Jewish ethnic groups. No blood sample was received from four infants with NH, and one infant with NH was not notified. This study indicates that a neonatal screening program can effectively detect infants with NH, resulting in earlier treatment. PMID- 4019142 TI - Multivariate analysis of prognostic factors in chronic lymphocytic leukemia. AB - Prognostic factors in a group of 90 patients with chronic lymphocytic leukemia were studied by methods of survival analysis. The relationship between survival and a set of demographic, clinical and laboratory variables, and identification of subsets of variables that are associated with survival, was tested by multivariate analysis, which is based upon Cox proportional hazards regression models in a stepwise procedure. Six variables showed significant correlation with survival: lymph node enlargement, splenomegaly, hepatomegaly, increased percentage (greater than 80%) of lymphocytes, hyperuricemia, and anemia. Stepwise analysis showed that the number of coexistent risk factors was a better predictor of survival than any single risk marker (P less than 0.001). Median survival of patients with 0 or 1 risk marker was 120 months; with 2 or 3, 96 months; with 4, 36 months; and with 5 or 6, only 24 months. Comparison of staging by number of risk markers with staging of the same patients by the Rai system showed a significant trend of decreasing survival with increasing number of risk markers within the same Rai stage. Staging by the number of coexistent risk markers is a simple and readily available method, which may complement existing methods to provide a more accurate assessment of prognosis in patients with chronic lymphocytic leukemia. PMID- 4019143 TI - Nutritional status of a population assessed on the basis of a group of blood donors. AB - Several blood constituents were used to evaluate the nutritional status of a random, consecutive group of 655 blood donors. The population included 503 men and 152 women, with a mean age of 35.1 years; 26.8% of the women and 26.5% of the men had deficient levels of ascorbic acid; 18.0% of the women an 11.9% of the men had hemoglobin levels below normal. Plasma iron was inadequate in 29.3% of the women and 18.6% of the men. A very small number of donors were found to be deficient in carotene, retinol, thiamine, riboflavin and pyridoxine. These findings call attention to an unexpected aspect of nutrition in an apparently healthy, not undernourished population. PMID- 4019144 TI - Echocardiographic findings of mitral and tricuspid valve prolapse in primary pulmonary hypertension. AB - Echocardiographic findings in six patients with primary pulmonary hypertension are presented. Four of six patients had abnormal septal motion with prolapse of mitral and tricuspid valves. The other two had none of the three echocardiographic abnormalities. It is possible that hemodynamic changes in ventricular pressure gradients across the interventricular septum cause an abnormal septal motion and secondary AV valve prolapse. PMID- 4019145 TI - Local anesthesia in carotid endarterectomy: an alternative method. AB - Results of carotid endarterectomy (41 operations) carried out under local anesthesia are presented. There were no deaths within 30 days. Three patients had undergone surgery with a temporary internal shunt, following signs of neurological changes (unconsciousness, aphasia, motor changes) during 1-min test cross-clamping. No neurologic deficits were observed, and only two patients (4.8%) experienced postoperative hypertension. These data support the view that simple neurological monitoring of awake patients enables accurate assessment of the need for an internal carotid shunt. Carotid endarterectomy under local anesthesia seems to be a very safe procedure. Use of this technique is especially appropriate for elderly patients with hypertension and ischemic heart disease. PMID- 4019146 TI - Transperitoneal migration and ovum capture in rabbits. AB - It is not fully understood how eggs are captured by the fallopian tube. The close proximity of tube and ovary, and the movements of the fimbria across the ovarian surface during ovulation, are believed to contribute to ovum pickup. We studied the efficiency of ovum capture when contact between fimbria and ovary is prevented and the extent to which ovum transmigration may contribute to fertility. Unilateral right oophorectomy was performed in 55 rabbits, which were divided into three groups: in Group A, the contralateral oviduct was left intact; in Group B, the ampulla of the contralateral oviduct was occluded; in Group C, contralateral total salpingectomy was performed. None of the rabbits in Group A conceived on the oophorectomized side. Seven of 19 animals became pregnant in Group B and 15 of 18 conceived in Group C. The results indicate that direct fimbrial-ovarian contact is not essential for ovum capture, and that ovum transmigration could contribute to fertility. PMID- 4019147 TI - Pheochromocytoma of the organ of Zuckerkandl presenting as shock. AB - A patient with unusual manifestations of pheochromocytoma, together with a relatively rare localization of the tumor in the organ of Zuckerkandl, is presented. There was a sharp fall in blood pressure to shock levels and transient severe cardiomyopathy, as evidenced by ECG changes, all of which disappeared postoperatively. We suggest several explanations for these unusual manifestations. PMID- 4019148 TI - Pediatric traumatic spinal cord injuries in Israel. PMID- 4019149 TI - X-ray findings of peripheral joints in essential cryoglobulinemia. PMID- 4019150 TI - Gentamicin-digoxin interaction in the rat kidney. PMID- 4019151 TI - Prenatal diagnosis of cystinosis upon exposure of amniotic cells to cystine dimethyl ester. PMID- 4019152 TI - Hypoglycemic and life-prolonging properties of Gymnema sylvestre leaf extract in diabetic rats. PMID- 4019153 TI - Crepitant cellulitis due to Enterobacter aerogenes. PMID- 4019154 TI - Incidence of pyloric stenosis in northern Israel. PMID- 4019155 TI - Endoscopic reduction of acute gastric volvulus complicating motor neuron disease. PMID- 4019156 TI - Recurrent instability of the gleno-humeral joint. AB - The importance of instability in the determination of painful syndromes of the shoulder is examined, with particular reference to young people who engage in sport. The physiopathology and clinical features are described, and the importance of diagnostic tests is emphasized. These often disclose the underlying pathological anatomy. Surgical treatment, which is indicated whenever the lesion is well documented, follows the methods used in treating recurrent dislocation. The validity of the method of Latarjet and Bristow is emphasized. PMID- 4019157 TI - Growth disturbances following fractures of the femur and tibia in children. AB - Growth disturbances can occur following fractures of the femur or tibia in children. They can produce lengthening, shortening, axial and rotational deformities. The number of variable factors involved is such that valid statistical analysis demands a very large series of well documented cases followed up until growth ceases or stabilisation is established. We hope to inaugurate such a survey in collaboration with other large centers. In the present limited survey of 174 the only statistically valid conclusions were that age and type of treatment are relevant factors in producing lengthening. In the other factors investigated the survey was not large enough to provide valid answers. It has been established that after metaphyseal or diaphyseal fractures in children disturbances of growth may occur resulting in accelerated growth, retarded growth, axial deformities and rotational deformities. The literature, although extensive, leaves many questions unanswered while on other matters, such as the role of certain factors in the pathogenesis of these disturbances, there is often conflicting data. In a brief review of the literature we decided to simplify our research by confining our observations to data relating only to single diaphyseal fractures. PMID- 4019158 TI - Growth disturbances following fractures of the femur and tibia in children. AB - We reviewed 160 diaphyseal and metaphyseal fractures of the femur and tibia in children treated between 1964 and 1980 at the Orthopaedic and Traumatological Clinic of the University of Rome. The initial documentation was complete in these cases and 96 presented for clinical and radiographic long-term follow-up. The analysis of this material showed that lengthening of the affected limb had occurred in 46% of cases. The amount of such lengthening, however, was only from 0.5 to 1.5 cm and never exceeded 2 cms. It was most frequent in children between the ages of 3 to 8 years with fractures of the tibia, particularly in the upper third of the bone. PMID- 4019159 TI - Growth disturbances following fractures of the femur and tibia in children. AB - During a period of 10 years we treated 855 children aged from 1 to 13 years suffering from diaphyseal fractures of the femur or tibia. From this material we were able to compile statistics regarding age, type and level of fracture, quality of reduction and duration of traction. From this material we were able to follow-up 357 fractures at a minimum of 3 and a maximum of 12 years with a view to evaluating the incidence of dysmetria in relation to age, level of fracture, and the presence of compensatory scoliosis. Our survey showed that lengthening due to growth disturbance following fractures is more frequent in fractures of the middle third of the bone in children in the 5-9 years age group. It also showed that spontaneous correction of axial deformities during growth is more likely to occur in the sagittal plane than in the frontal plane. The radiographic survey showed constant thickening of the fractured diaphysis with sclerosis of the load bearing cortex and thinning where the cortex is under tension. PMID- 4019160 TI - Growth disturbances following fractures of the femur and tibia in children. AB - The authors reviewed 477 diaphyseal fractures of the long bones in the lower limbs of children between the ages of one to 11 years treated at our Institute between 1976 and 1982. The objective was to evaluate the incidence and extent of post fracture lengthening and its possible relationship to the method of treatment. The amount of lengthening observed never exceeded 2 cms. and this always occurred in the early months after injury and then ceased. There was no statistical relationship with the method of treatment or with the type of fracture. For any valid assessment of such statistics, however, it would be necessary first to know the incidence of lower limb dysmetria in a similar group of normal children who had not sustained fractures. PMID- 4019161 TI - The importance of the angle of anteversion in the development of arthritis of the hip. AB - The angle of anteversion, assessed by the Dunlap technique, was determined in 30 patients suffering from primary osteoarthritis of the hip. This was compared with the same angle in 10 normal subjects. The patients with arthritis showed a statistically significant increase in the angle. This is considered by the authors to play a significant part in the pathogenesis of primary osteoarthritis of the hip. PMID- 4019162 TI - Stable fixation of fractures of the forearm in adults. AB - The results are presented of 148 fractures of the radius and ulna in 89 patients. All were treated by AO compression plating. The results were assessed at an average of 4.5 years. In 80% of cases these were functionally excellent and confirm that this method of treatment gives early consolidation and restoration of good function in adults. However, there is a significant percentage of complications in open fractures of both bones. PMID- 4019163 TI - Rotatory subluxation of the atlanto-axial joint. AB - Twelve cases of rotatory subluxation of the atlanto-axial joint are presented. The pathogenesis of this lesion is discussed, in particular why it is prevalent in children. The radiographic and clinical features are described. The long-term results emphasize the importance of early diagnosis and treatment, which are essential if the best results are to be obtained. PMID- 4019165 TI - Transposition of the 5th to the 4th ray by osteotomy of the hamate. AB - The authors present 5 cases of transposition of the 5th to the 4th ray according to Le Viet's method. This is indicated for the aesthetic and functional defects that follow total or subtotal amputation of the ring finger. The technique consists of radial transposition of the whole ray and intracarpal arthrodesis after cuneiform osteotomy of the hamate bone. It is easier to perform than the traditional metacarpal osteotomy and the results were uniformly good. PMID- 4019164 TI - Osteogenesis imperfecta. A study of 10 cases. AB - From a retrospective study of 10 cases of osteogenesis imperfecta the authors have verified the usefulness of the classification proposed by Sillence. This has particular advantages in relation to correct prenatal diagnosis and genetic counselling. PMID- 4019166 TI - The Risser plaster corset as the only method of correction in the surgical treatment of scoliosis. A study of 150 cases. AB - The authors analyse a consecutive series of 150 vertebral arthrodeses for scoliosis in which Risser's plaster technique was used as the only method of achieving correction. The results are analysed in relation to the most important factors in order to make them suitable for comparison with similar cases treated by the Harrington instrumentation method, the main justification for which is the reduced period of immobilisation. The results of the Risser technique compare favourably with those of the Harrington technique, in addition to which they showed several advantages. PMID- 4019167 TI - Acetabular wear in Charnley's polyethylene prosthesis. AB - During the last 13 years, 747 Charnley total prostheses were carried out. These cases have been critically reviewed in relation to the phenomenon of wear of the acetabular polyethylene. The possibility and limitations of measuring this radiographically are considered. The statistical data obtained is discussed and the acetabular wear is evaluated in relation to the length of time since the prosthesis was inserted. PMID- 4019168 TI - Some new aspects of the functional anatomy of the shoulder. AB - The authors investigated the functional role of the shoulder muscles in various active movements using simultaneous polymyographic recordings. Ten muscles were investigated in both normal subjects and in patients with pathological conditions. Ten patients were also studied during the course of operations for nonrelated conditions by "tetanizing" stimulation of nerves to individual muscles to determine their action as single muscles. PMID- 4019169 TI - The pathology of the rotator cuff of the shoulder. AB - The pathology of the rotator cuff of the shoulder, which is often regarded as synonymous with the condition known as peri-arthritis of the shoulder, comprises: calcified tendinopathy, tendinosis, the acromio-humeral friction syndrome and rupture of the rotator cuff tendons. The authors analyse the various aspects of these pathological conditions in the light of recent physiopathological and clinical findings. PMID- 4019170 TI - The fieldworker as watcher and witness. PMID- 4019171 TI - When X rays show, must prison doctors tell? PMID- 4019172 TI - The final, anticlimactic rule on Baby Doe. PMID- 4019173 TI - Inguinal hernia repair using the Shouldice technique--an experience of 101 cases. PMID- 4019174 TI - Malpractice insurance--what can happen if you don't have it. PMID- 4019175 TI - Fulminating pulmonary cryptococcosis responsive to sulfadiazine. PMID- 4019176 TI - Concubine syndrome: an example of interactionism in the clinical assessment of headache. PMID- 4019177 TI - Dietary factors in migraine precipitation: the physicians' view. PMID- 4019178 TI - An approach to the nature of tension headache. PMID- 4019179 TI - Headache in the rural village of Quiroga, Ecuador. PMID- 4019180 TI - Migraine and muscle contraction headaches: a continuum. PMID- 4019181 TI - The influence of plasma free fatty acids and cholesterol on the aggregation of blood platelets in migraine patients. PMID- 4019182 TI - Headache as the leading symptom of the thoracic outlet syndrome. PMID- 4019183 TI - Are classical and common migraine different entities? PMID- 4019184 TI - Cigarette smoking and cluster headaches. PMID- 4019185 TI - Migraine and mitral valve prolapse. PMID- 4019186 TI - [The malignant melanoma in situ: the flat, curable stage of malignant melanoma]. PMID- 4019187 TI - [Hydroa vacciniforme--urocanic acid content of the horny layer of the epidermis]. AB - Urocanic acid was measured by means of high-performance liquid chromatography (HPLC) in the stratum corneum of a 3.5-year-old child suffering from hidroa vacciniformia. Compared to ten healthy children of equal age, the urocanic acid content of the stratum corneum was reduced significantly. In addition, there was an elevated level of some amino acids in the urine, particularly that of histidine and methylhistidine, which seems to be a very important finding. Urocanic acid acts as a natural sun protective agent, and the results are discussed with this in mind. It was not possible to elicit hidroa vacciniformia lesions in the patient by UV-A, as described by others. PMID- 4019188 TI - [Epidermolysis bullosa dystrophica Bart (Bart syndrome)]. AB - This is a report on a child with epidermolysis bullosa dystrophica Bart (Bart's syndrome), which is characterized by the following symptoms: congenital, localized absence of skin; blistering of skin and mucous membranes only in the first years of life; absence and deformity of nails. The favorable prognosis of this disease, with spontaneous improvement of the blistering, emphasizes the importance of knowledge of this rare syndrome. PMID- 4019189 TI - [Artificial penile nodules (tancho nodules) in Southeast Asian men]. AB - Especially in Thailand, but also in other countries in Southeast Asia, the practice of implanting glass or other kinds of beads in the subcutaneous tissue of the penis for the purpose of increasing the sexual pleasure of the partner has become common. The inserted glass beads do not usually give rise to symptoms and normally they are only detected by chance. Here we describe our experience with a 27-year-old Thai with a penile nodule made from the polished material of a tooth brush. PMID- 4019190 TI - [Pemphigus vegetans (Hallopeau) with eosinophilic spongiosis--successful retinoid therapy]. AB - We present an unusual case of pemphigus vegetans (Hallopeau) with widespread, nonblistering gyrate erythematous lesions on the trunk and extremities in addition to typical vegetating lesions in the inguinocrural area. The histopathology which was characterized by eosinophilic spongiosis, as well as immunofluorescence and immunoelectron-microscopic studies indicated that the gyrate erythema (characterized by eosinophilic spongiosis) seen in our patient represented a manifestation of pemphigus. Treatment with retinoids resulted in the prompt disappearance of the gyrate erythemas, and the eosinophils returned to normal. A short-term, low-dose corticosteroid regimen also led to rapid healing of vegetating lesions. PMID- 4019191 TI - [The so-called nasal glioma]. AB - A case of nasal "glioma" is presented. This tumor consists of congenital heterotopic glial tissue and represents an abnormal protrusion of brain substance (exencephalia). PMID- 4019192 TI - Comparison of the ICRP and MIRD models for Fe metabolism in man. AB - A task group of the Medical Internal Radiation Dose (MIRD) Committee has recently published a model of Fe metabolism in man. This model was developed to calculate doses from radioiron injected for medical diagnostic purposes. It is a compartment model with recirculating Fe exchanging between plasma and extracellular fluids, tissue storage compartments, bone marrow and red blood cells (RBC). It is a first order model with the exception of Fe in the RBC compartment, which is assumed to retain Fe for 120 days, at which time the Fe returns to the extracellular fluid compartment. By contrast, the International Commission on Radiological Protection (ICRP) model is a "once through" first order compartment model, with the compartments represented by organs (spleen, liver and other soft tissue) rather than physiological compartments as in the MIRD model. Both of these models have been implemented in the computer code GENMOD which contains the ICRP recommended lung and gastrointestinal tract models and which is used at the Chalk River Nuclear Laboratories to calculate doses, excretion rates, derived investigation levels, etc. The results of calculations using these models have been compared to see if the much less sophisticated ICRP model was adequate for radiation protection purposes. It was found that the effective dose per unit intake of radioiron was higher for the MIRD model and urinary excretion rates following an exposure were considerably different. It is concluded that the ICRP model should not be used in dosimetry calculations, or for comparing monitoring results to model calculations. PMID- 4019193 TI - Hazard analysis technique for multiple wavelength lasers. AB - A technique for evaluating the potential hazards from multiple wavelength lasers is described below. Since little or no known multiwavelength laser exposure research has been performed, this technique is not substantiated and should be employed with great care. PMID- 4019194 TI - Measurement of gamma radiation exposure rates from natural UO2 fuel pellets. AB - An attempt has been made to measure gamma radiation exposure rates from natural UO2 fuel pellets at near contact distances by means of a GM survey meter and LiF thermoluminescent dosimeters. An experimental device was fabricated which facilitated the holding of both the fuel pellets and the necessary measuring devices. A semi-empirical method for predicting exposure rates from a fuel pellet at near contact distances is also described. It is suggested that the experimental set up has the potential for providing a calibration device for gamma radiation instrumentation used to assess exposures in facilities handling U. PMID- 4019195 TI - Transport of elements from soil to human diet: an alternative approach to pathway analysis. AB - Transport from soil to human dietary intake is conventionally treated by analyzing the various pathways through uptake by plant roots and transfer from animal feed into milk and meat. An alternative approach is proposed requiring only the average daily human ingestion of each element and its abundance in soil, both readily available for most elements. The two methods are compared quantitatively and give results consistent within a mean factor of four, which is roughly the standard deviation in estimates from the pathway analysis. Neither method gives consistently larger or smaller transfer rates. Each method has important advantages in some applications. PMID- 4019196 TI - A field study of Ra accumulation in trout with assessment of radiation dose to man. AB - The purpose of this study was to determine the concentrations of 226Ra in edible fish from surface ponds near an open pit U mine. Because one reclamation plan for the U mine proposed formation of an artificial lake in the open pit, potential radiation dose to man from ingestion of fish needed to be investigated. Trout were collected from four existing ponds which varied in mean 226Ra concentration from 12-33 pCi/l. and in Ca concentration from 30-330 mg Ca/l. Radium and Ca accumulation in trout flesh, skin, fins and bone were measured. Geometric mean concentrations of 226Ra in trout flesh from four ponds ranged from 6.3-30 pCi/kg wet weight. The distribution of Ra in the trout body was similar to that of Ca. Of the total 226Ra in trout carcasses, 6% was in flesh, 25% was in skin, 28% was in fins, and 41% was in bone. Mean concentration factors for 226Ra in trout flesh from the four ponds ranged from 0.29-2.5. Bone concentration factors were up to 260 times higher than for flesh. Observed ratios (Ra/Ca in fish tissue divided by Ra/Ca in water) were used to normalize the differences in Ca availability among the locations. Observed ratios were higher in all tissues of fish which had been in the ponds for a longer time, indicating that 226Ra concentrations in fish may increase with continued exposure to the nuclide. The calculated dose equivalent commitment to human endosteal tissue ranged from 0.2-2 mrem per fish consumed, depending on the assumed dietary and environmental parameters. Neglecting the consumption of trout skin underestimated the ingestion dose from 226Ra by a factor of 5-10. Estimated annual dose equivalent rates to human endosteal tissue ranged from 1.0-83 mrem/yr for an individual who consumed one fish per week for a 50-yr period. The dose to man from ingestion of 226Ra in fish would not likely preclude the establishment of a recreational lake at this site. PMID- 4019197 TI - Use of computer memory chips as the basis for a digital albedo neutron dosimeter. AB - We have measured the sensitivity of commercially available dynamic random access memories (D-RAMs) to alpha particles. Using a beam of 14-meV neutrons and a 6LiF crystal as a converter we have measured sensitivities to neutron radiation as high as 9.25 memory errors per millirem. We estimate that an optimized converter would produce even higher sensitivities as an albedo dosimeter in realistic radiation fields. Such a device would have a number of operational advantages. PMID- 4019198 TI - The origin of I in soil and the 129I problem. AB - It is widely believed that the I in soil is derived from the I in oceans by evaporating-atmospheric transport-washout by rain over land, rather than from the I in rock when the latter is weathered into soil. Since human I burdens are derived largely from soil by plant root uptake into food, this implies that the specific activity of 129I in the I of human thyroids will be the same as that in the oceans, whereas it would be similar to that in rock (much lower) if the I in soil were derived from weathering of rock as is the case for other heavy trace elements. The bases for the oceanic origin theory are analysed and found not to be in accord with modern data. Recent data shows no correlation between concentration of I in soil and proximity to oceans, which argues strongly against the oceanic origin theory. Some problems with long-distance atmospheric transport are pointed out. It is shown that the balance between I input to soil during soil formation by rock weathering and output from soil by erosion leaves little room for contributions from oceanic sources. It is concluded that only a small fraction of the I in soil is of oceanic origin. Most estimates of very long-term effects of 129I on human health are therefore several times too high. PMID- 4019199 TI - Potassium iodide: predistribution or not? The real emergency preparedness issue. PMID- 4019200 TI - In-vitro monitoring of salivary 125I. PMID- 4019201 TI - Plutonium-239, 240Pu and 210Po contents of tobacco and cigarette smoke. PMID- 4019202 TI - Gamma activity of the fly ash from a Greek power plant and properties of fly-ash cement. PMID- 4019203 TI - Plutonium in autopsy tissues in Great Britain. PMID- 4019204 TI - Energy and angular distribution of 60Co gamma rays in air. PMID- 4019206 TI - Guidelines for issuing personnel dosimeters. PMID- 4019205 TI - Comments on the paper 'Measurement of the effective dose equivalent in a nuclear reactor environment with a personal thermoluminescent dosimeter'. PMID- 4019207 TI - Hazards from sinking of ships with U cargo. PMID- 4019208 TI - B. L. Cohen's probabilities for human intake and implications for nuclear waste disposal. PMID- 4019209 TI - Disposal of laboratory-generated liquid radioactive waste. PMID- 4019210 TI - Guidelines on limits of exposure to ultraviolet radiation of wavelengths between 180 nm and 400 nm (incoherent optical radiation). The International Non-Ionizing Radiation Committee of the International Radiation Protection Association. PMID- 4019211 TI - Guidelines on limits of exposure to laser radiation of wavelengths between 180 nm and 1 mm. International Non-Ionizing Radiation Committee of the International Radiation Protection Association. PMID- 4019212 TI - Factors associated with variation in financial condition among voluntary hospitals. AB - This article uses multiple regression analysis to identify factors which affect variations in the financial condition of voluntary hospitals in New York State. Six separate ratios are used to measure financial condition and 18 independent variables are considered. The factors affecting financial conditions were found to vary among dimensions of financial health, and different causal relationships were evident among hospitals in New York City than among those in the rest of the state. PMID- 4019213 TI - Validation of the patient roster in a primary care practice. AB - Knowledge of the size of a practice population is an essential base for the evaluation of new forms of health care delivery and for epidemiologic research in primary care. Remuneration to providers in Ontario's Health Service Organization and Health Centre programs is partially based on the number of people listed on the patient roster as members of the practice. However, the accuracy of these rosters has never been determined. A mail and telephone survey was conducted to validate the roster in one such health center. A random sample of 1,065 households was contacted and a 78 percent response rate was obtained. The practice roster showed a population of 3,134. The age- and sex-adjusted estimate from the survey was 2,964 (+/- 262) individuals. The sensitivity, specificity, and accuracy of the roster were 0.90 or greater. It is concluded that this particular roster is a valid indicator of practice size, but caution is expressed about generalizing these results to other practices. PMID- 4019214 TI - Independent versus system-affiliated hospitals: a comparative analysis of financial performance, cost, and productivity. AB - This article analyzes differences in the financial performance, cost, and productivity between system-affiliated and independent hospitals. Data for the study were obtained from the 1981 American Hospital Association (AHA) Annual Survey of Hospitals for the State of Iowa and included 94 nonstate or nonfederal short-term hospitals without long-term care units. An interpretation of the results indicated that system-affiliated hospitals are more profitable, have better access to capital markets, are more effective price setters, and experience higher costs per case which are related to longer lengths of stay and less productive use of plant and equipment in generating revenues. PMID- 4019216 TI - Enzyme heterozygosity associated with anatomical character variance and growth in the herring (Clupea harengus L.). AB - The hypothesis that enzyme heterozygosity is positively related to phenotypic characteristics in fish was tested using five polymorphic enzyme loci and seven anatomical characteristics in samples of North Irish Sea herring, Clupea harengus. Though not unambiguous the results indicated that heterozygosity was associated with increased developmental stability. Also, multiple homozygosity was negatively correlated with growth parameter estimates. Though no single locus correlates were evident, the level of multiple heterozygosity of an individual appeared to be positively related to body length. PMID- 4019215 TI - Census tract predictors of physical, psychological, and social functioning for needs assessment. AB - The advantages of census data-based needs assessment cannot be fully realized in the absence of demonstrated relationships between area characteristics and aggregate individual service need. This study sought to ascertain these relationships by using tract characteristics from the 1980 census to predict tract aggregate levels of individually measured social, physical, and psychological functioning. A census tract stratified sample of 3,465 permanent households in eastern Long Island, New York was used for the study. In each household, a randomly selected adult was surveyed regarding physical functioning, depressed mood, and social isolation. Stepwise multiple regression was used to determine which census variables best predicted the tract distributions of each of the functioning measures. Census variables explained from 23 to 30 percent of the variance in tract need level. Study findings have immediate utility for efficient needs assessment and suggest avenues for future improvement of needs assessment methods. PMID- 4019218 TI - Diallel designs, analyses, and reference populations. AB - Some issues which evidently remain as areas of contention in diallel analysis are reviewed. In the estimation of genetic variance components for an ancestral reference population in equilibrium, analysis should be applied to F1 data only, and proceed as for a random effects model. No meaningful reference population is constituted by the parental sample itself, but an equilibrium reference population which could be derived from these parents can be defined. To give unbiassed estimates of parameters for this population, analysis must include S1 data, and the parents must be homozygous and in linkage equilibrium. Estimation of dominance variance must allow for the fact that the diallel population itself is not in linkage equilibrium by correcting the specific combining ability sum of squares for the mean S1 vs. F1 difference. Some different analyses of variance of the diallel table are discussed in the context of the above reference populations. PMID- 4019217 TI - Genome size variation among north american minnows (Cyprinidae). I. Distribution of the variation in five species. AB - Genome sizes (nuclear DNA contents) were examined spectrophotometrically from ten individuals of each of five species of North American cyprinid fishes (minnows). The distributions of DNA values both within and between the five species were essentially continuous and normal. Differences between individuals within populations were significant and contributed to approximately 16 per cent of the total variation. Variation between individuals within species ranged from 4.7 13.5 per cent and averaged ca. 7.4 per cent. Variation between species ranged from 0-9.5 per cent and the average difference between any species pair was ca. 4.6 per cent. Statistical analyses showed that the methodology used was sufficient to detect significant differences in genome size as small as 2-3 per cent. Consideration of these data lead to the following tentative conclusions: (i) changes in genome size in cyprinids appear small in amount, frequent in occurrence, to involve both gains and losses of DNA, and to be cumulative and independent in effect; (ii) differences within and between cyprinid taxa are likely the result of accumulations of small changes in DNA quantity; and (iii) the primary focus of quantitative DNA variation in cyprinids is between individuals within populations. The extent of DNA quantity variation which occurs within species would appear to preclude any direct relationship between genome size variation and many of the organismal parameters (including speciation) which differentiate the five species. In short, the data suggest that a significant fraction of the cyprinid genome, perhaps more than 10 per cent, is free to vary quantitatively without phenotypic constraint or biological consequence. This fraction is considerably larger than that theoretically needed for the structural gene component. PMID- 4019219 TI - Heterozygosity and morphological variability of chum salmon (Oncorhynchus keta) in southern British Columbia. AB - We compared variability in two meristic and six morphometric characters with heterozygosity within and among 27 populations of chum salmon (Oncorhynchus keta) in southern British Columbia. Among individuals, there was no relationship between levels of heterozygosity at 10 electrophoretic loci and degree of meristic or morphometric variation. Decreased morphological variance was not associated with increased heterozygosity. Morphological variance and heterozygosity did not change with age for chum salmon maturing at three to five years of age. Among populations of chum salmon, increased levels of average heterozygosity were not associated with decreased variance of morphometric or meristic characters. Our results do not support the hypothesis that more heterozygous individuals show less phenotypic variability than more homozygous ones due to a canalization of morphology during development. Genetic distances between pairs of chum salmon populations were significantly correlated with pairwise Mahalanobis distances derived from meristic, but not from morphometric characters. Chum salmon are morphometrically adapted to the natal stream environment, whereas biochemical and meristic characters in these populations may be less affected by local selective forces. PMID- 4019220 TI - The fixation of chromosomal rearrangements in a subdivided population with local extinction and colonization. AB - The fixation of major chromosomal rearrangements with a heterozygote disadvantage is modelled as a simple example of Wright's shifting balance process of evolution in a strongly subdivided population. Chromosomal mutations with an inferior heterozygote become fixed in a local population (or deme) by random genetic drift and spread by migration and colonization. Wright postulated a process of selective diffusion in which the numbers of emigrants and colonizers dispersed from a deme increase with the mean fitness of individuals in it. The present models show that interdeme selection during the spread of a mutation depends more on the capacity of the mutant to invade and become established in other demes than on selective diffusion, unless there is rapid local extinction and colonization. The intensity of interdeme selection is reduced by random local extinction and colonization, and when these processes are rapid (with no selective diffusion) the expected fixation rate of spontaneous mutations with a heterozygote disadvantage approaches that in a single isolated deme. Local extinction and colonization, and selection on the homozygotes, accelerate the spread of chromosomal mutations which are destined to be fixed. PMID- 4019221 TI - Predicting the properties of first cycle inbreds and second cycle hybrids extractable from two, three and four parent crosses. AB - Standard biometrical genetical models of Mather and Jinks (1982) when made applicable to the means and variances of the 55 early generations produced by crossing four parents and six F1's in all possible combinations provide estimates of genetic parameters that can be used to predict the distributive properties of the first cycle inbreds and second cycle hybrids which could be extracted from any of these generations. Thus we can predict the inbreeding and outbreeding potentials of each generation in the early stages of a breeding programme and formulate the best breeding strategy for harnessing the full genetic potential of the breeding material and choosing the best end product. The 55 generations provide reliable estimates of the predictors and therefore should be used whenever possible. Simpler experiments consisting of the basic generations of the six single crosses, however, are sufficient for obtaining estimates of the predictors of the inbreds and can be used to predict their properties when information about the second cycle hybrids is not required or the remaining generations are not available. Replacement of the F2, backcross, three way cross and double cross generations with their randomly mated progenies is expected to improve the accuracy of predictions in the presence of a linkage disequilibrium. However, the gains made may not be justified against the costs of the additional breeding and the delay in making the predictions. Extensive experimental testing of the theory of these procedures must await the completion of the current field experiments. In the meantime the limited tests conducted on the material extracted from the Nicotiana rustica varieties V1, V2, V5 and V12 have confirmed the familiar conclusions that the V1 X V5 and V2 X V12 differ in their inbreeding and outcrossing potentials. PMID- 4019222 TI - A graphical aid to medical decision making. PMID- 4019224 TI - Metastatic bronchogenic carcinoma simulating osteoarthritis. PMID- 4019223 TI - Diagnosis of hepatic portal venous gas by computed tomography: role of intravenous contrast material. PMID- 4019225 TI - Leiomyosarcoma of the heart: a twenty-year cure. PMID- 4019226 TI - Central pontine myelinolysis in a patient with adrenal insufficiency. PMID- 4019227 TI - The invalidity of monitoring transcutaneous oxygen tension in patients who have chronic renal failure. PMID- 4019228 TI - Development of information system for biochemical study in central laboratory. PMID- 4019229 TI - Influence of amines in the brain and gastric wall on development of stress ulcers. PMID- 4019230 TI - Surgical treatment of pancreatic cysts: review of 21 cases. PMID- 4019231 TI - Pyogenic liver abscess: a study of 18 patients. PMID- 4019232 TI - A comparison of pancreatectomy and pancreatic duct drainage in chronic pancreatitis. PMID- 4019233 TI - Ascitic bile acids in patients with liver cirrhosis. PMID- 4019234 TI - Relationship between the decrease of cytotoxic antibody with the elapse of time and hyperacute rejection in hyperimmunized rats. PMID- 4019235 TI - Studies on the control of hyperacute rejection in hyperimmunized rat: combination of donor specific blood transfusion (DST) and immunosuppressive drugs. PMID- 4019237 TI - An analysis of cardiopulmonary hemodynamics during hemorrhagic shock in dogs. PMID- 4019236 TI - Gastric mucosal lesions in cases of nonshunting procedures for esophageal varices. PMID- 4019238 TI - Some statistical issues pertaining to in vitro drug testing with human tumor colony forming assays. PMID- 4019239 TI - A case report of bronchogenic cyst in an infant causing acute respiratory distress. PMID- 4019240 TI - Flow cytometric assessment of neutrophil oxidative metabolism in chronic granulomatous disease on small quantities of whole blood: heterogeneity in female patients. PMID- 4019241 TI - Zinc, copper, and manganese concentrations in cerebrospinal fluid of patients with viral meningitis. PMID- 4019242 TI - Comparison of free amino acid concentrations in eosinophils and neutrophils. PMID- 4019243 TI - Effect of splenectomy on free amino acid concentrations in erythrocytes of patients with hereditary spherocytosis. PMID- 4019244 TI - Experimental studies on acute gastric mucosal lesion involved with obstructive jaundice: mainly on the changes of amine contents in the gastric mucosa on cold restraint stress. PMID- 4019245 TI - Depression of luminol-enhanced chemiluminescence of guinea pig polymorphonuclear leukocytes by influenza virus with special reference to neuraminidase. PMID- 4019246 TI - Application of 7-amino-actinomycin D for the fluorescence microscopical analysis of DNA in cells and polytene chromosomes. AB - The cytochemical properties of a guanine-specific synthetic fluorescent analogue of actinomycin D, 7-amino-actinomycin D, have been studied in fixed and living preparations of L cells and polytene chromosomes of salivary glands of Chironomus thummi thummi and Drosophila lummei (Hackman). 7-Amino-actinomycin D has been shown to bind to DNA-containing structures, thereby inducing in them a bright red fluorescence. No specific fluorescence has been found in RNA-containing structures treated with this fluorescent probe. The fluorescence pattern of some regions of polytene chromosomes with a known nucleotide composition was analysed. It has been established that 7-amino-actinomycin D induces a very weak fluorescence in GC-poor chromosome regions of the Drosophila lummei toromere structure. Data indicating a nonlinear dependence between the fluorescence intensity of a stained chromosome region and the GC content in its DNA have been obtained. The influence of DNA nucleotide composition in a chromosome region on the fluorescence of 7-amino-actinomycin D is discussed. In combination with quinacrine staining and the Feulgen fluorescence reaction, treatment with 7-amino actinomycin D provides useful information about the distribution of GC base pairs in the chromosome region under study. PMID- 4019248 TI - Chemical and histochemical studies of normal and diseased gastrointestinal tract. IV. A comparison of histochemical and chemical methods for the estimation of side chain O-acylated sialic acids. AB - Statistically significant correlations were obtained between a chemical assay for the proportion of colonic epithelial glycoprotein sialic acids with side chain O acyl substituents and two histochemical methods, the PBT-KOH-PAS sequence (rs = 0.7485 for N = 31, P = 0.01, one-sided test) and the PAPT-KOH-Bh-PAS procedure (rs = 0.7024 for N = 34). A positive correlation (rs = 0.8654 for N = 30, P = 0.01) was also obtained between the results of the two histochemical procedures. It is concluded that, on average, histochemical observations are a reliable semiquantitative comparative method for the estimation of side chain O-acetylated sialic acids. PMID- 4019247 TI - Chemical and histochemical studies of normal and diseased human gastrointestinal tract. III. Changes in the histochemical and chemical properties of the epithelial glycoproteins in the mucosa close to colonic tumours. AB - Histochemical, chemical and histological studies were performed on 26 specimens of human colonic tumours and 62 specimens of mucosa taken at distances of 0.5-5.0 cm from the tumour. The tumour glycoproteins were divided almost equally between three anionic types, sulphomucin, sialomucin and mixed sialomucin and sulphomucin. All showed a reduction in staining for side chain O-acylated sialic acid. In 56% of the tumours, this was accompanied by loss of glycoprotein while, in 44%, abundant mucin was still present. Histochemical examination of the mucosal specimens indicated that in 24.2% the side chain O-acylated sialic acids did not differ from normal. In 41.9% there was a focal change and in 33.9% there was a generalized field reduction in the proportion of side chain O-acyl sialic acids. The latter were subdivided into moderate and severe. Chemical analyses correlated well with the histochemical classification of the mucosal specimens and showed that, on average, the classifications focal and severe field change were not due to sampling error. Forty-five per cent of the cases showed only focal change and 40% only field change. Mucosal specimens associated with 60% of the moderately differentiated tumours showed only focal change while those associated with 75% of well-differentiated tumours showed only field change. Abnormal patterns of staining for side chain O-acylated sialic acids (a) were largely independent of the distance from the tumour, (b) occurred in the presence of a normal pattern of staining for sialomucins and sulphomucins and (c) were associated with 61.4% of the specimens that showed no discernible evidence of histological abnormality. In contrast, only one specimen showed evidence of histological change without a corresponding change in O-acylated sialic acids. The data suggest that abnormal patterns of staining for O-acylated sialic acids may represent premalignant change but their precise significance and specificity requires further studies of non-neoplastic diseases of the colon. PMID- 4019249 TI - Surface localization of an endogenous lectin in rabbit bone marrow. AB - A lectin, which may be involved in cell to cell adhesion during erythropoiesis in rabbit bone marrow, has been isolated and characterized. Several electron microscopical techniques have been used to investigate the cell surface distribution of this lectin in bone marrow utilizing colloidal gold conjugates of anti-lectin IgG or protein A. The lectin is present at the surface of erythroid cells at all stages of development but no lectin was detected on the surface of myeloid cells. The limitations and complementary nature of the techniques used are discussed. PMID- 4019251 TI - False localization of acid phosphatase activity in the nuclear envelope and endoplasmic reticulum of peritoneal macrophages. AB - Acid phosphatase cytochemistry using lead salt methods was performed on rat peritoneal macrophages obtained by the intraperitoneal injection of dextran five days previously. Lead precipitate was present in the nuclear envelope, the rough endoplasmic reticulum, Golgi apparatus and lysosomes in about 50% of these cells. The formation of reaction product appeared to be substrate-specific and was sensitive to sodium fluoride in all these sites. However, only in the nuclear envelope, the rough endoplasmic reticulum and Golgi apparatus could lead salt precipitation be prevented by (a) omission of the washing procedure following the incubation step, (b) postincubation in a medium containing sodium fluoride, or (c) washing in buffer containing lead salt. It is concluded that precipitation of lead salt does not prove the presence of acid phosphatase activity in these organelles. The formation of precipitate in these sites is probably due to a local matrix effect, facilitated by the persistence of acid phosphatase activity in the lysosomes and a suboptimal trapping efficiency of phosphate ions during the washing procedure which follows in the incubation step. PMID- 4019250 TI - Ultrastructural histochemistry of the surface lamina of normal articular cartilage. AB - Two collagen-poor, ultramicroscopic layers are described at the surface of canine articular cartilage. They are distinguished by staining with an electron-dense cationic dye, Cupromeronic Blue, in a critical electrolyte concentration technique and by digestion with testicular hyaluronidase. The superficial layer, approximately 50 nm thick, stained at low electrolyte concentrations but failed to stain in conditions specific for sulphated glycosaminoglycans. It was hyaluronidase-resistant and may be either glycoprotein or protein in nature. The deeper layer, 100-400 nm thick, stained positively at electrolyte concentrations specific for sulphated glycosaminoglycans but not in conditions specific for keratan sulphate. It was removed by hyaluronidase digestion. This layer probably represents a chondroitin sulphate-rich proteoglycan. These surface layers may be important in the lubrication of the articular surface and in the permeability and compression resistance of the superficial cartilage zone. PMID- 4019252 TI - Footnotes to food tables. 2. The underestimations of intakes of lesser B vitamins by pregnant and lactating women as calculated using the fourth edition of McCance and Widdowson's 'The composition of foods'. AB - In McCance & Widdowson's 'The composition of foods' many items lack information on the content of the lesser B vitamins, and dietary intakes can therefore be underestimated. The degree of this underestimation was assessed using data from a longitudinal study of the food intake of 63 pregnant and lactating mothers in Cambridge, UK, with a total of 3185 days of weighed diet records. The extra mean daily additional intake of each vitamin contributed by foods eaten by the mothers but lacking data in the food tables was estimated to be: vitamin B12, 0.1 micrograms, (1.5 per cent of total intake); vitamin B6, 0.04 mg (3.3 per cent); total folate, 10 micrograms (5.3 per cent); pantothenic acid, 0.6 mg (11.5 per cent); and biotin, 5 mg (14.3 per cent). Although many items in the tables lack data, most were eaten infrequently and made little contribution to vitamin intake. It was estimated that, if data were added for a limited number of frequently-eaten foods, namely, white toast, baked beans, biscuits, breakfast cereals and 'chicken with skin', then intakes of all five vitamins would be underestimated by less than 4 per cent. PMID- 4019253 TI - Dietary chromium and manganese intakes of a selected sample of Canadian elderly women. AB - Energy, manganese and chromium intakes of a selected sample of 90 free-living Canadian women (mean age 66.2 +/- 6.2 years) living in a university community and consuming self-selected diets were assessed by chemical analyses of 24-h duplicate diets and via three-day dietary records, collected by the subjects. Mean gross energy intake (determined via bomb calorimetry) was 6.0 +/- 2.4 MJ (1435 +/- 580 kcal) and mean intake of manganese (determined via atomic absorption spectrophotometry) was 3.8 +/- 2.1 mg/day, respectively. Mean and median chromium intakes, analysed via instrumental neutron activation analysis were 96.4 and 77.4 micrograms/day, respectively. The manganese and chromium densities of these diets were higher compared to diets for pre-menopausal women studied earlier, attributed in part to the higher (P less than 0.0003) median intake of tea (360 g) vs 180 g for the pre-menopausal women. No significant differences between the pre and post-menopausal groups in mean intakes (in g) of any other food groups investigated, were found. Silver-plated cutlery may also be a source of adventitious chromium in the diets of these post-menopausal subjects. Nevertheless 22 per cent of the subjects had chromium intakes based on one day duplicate diets, below the US suggested safe limit, which if representative of their habitual chromium intakes, may result in chromium depletion. PMID- 4019254 TI - Diarrhoea: after rehydration, what next? AB - Successful management of diarrhoea depends firstly on restoring fluid and electrolyte balance. Following this, the child needs to be fed, to prevent malnutrition and morbidity. Conventionally, this is achieved by regrading onto the previous feed. In our series of 42 infants with mild gastroenteritis, six out of 12 infants had persistent diarrhoea after one week on normal infant formula. Twenty-five out of 27 infants who were given a low-lactose formula (HN25) had normal stools within 4 days. (chi2 = 18.487; P less than 0.001). Only two out of 27 infants had a recurrence of loose stools at 1 week and these became normal after regrading back on to HN25. Recovery time was shortened, while nutritional status was maintained. Short-term substitution of a low-lactose formula after rehydration speeds recovery from gastroenteritis. PMID- 4019255 TI - Nutrient intake and anthropometric assessment of patients at home after partial gastrectomy or vagotomy. AB - Ten patients, six of whom had had a partial gastrectomy and four a vagotomy, took part in the study. Anthropometric measurements, weighed dietary intakes, social circumstances and amount of dietary advice and help received by patients were recorded during the first month and at 7 months after discharge from hospital. Anthropometric measurements changed little during the first month but improved in most of those with lower than normal initial values by the end of 7 months. Mean energy and protein intakes during the first month were low for the gastrectomy patients but were adequate for the vagotomy patients. By 7 months the intakes of the gastrectomy patients had increased considerably. Mean intakes of vitamin C, total folate and zinc tended to be low in both groups and mean intakes of iron were low in the gastrectomy patients. No patient ate an entirely satisfactory diet. Very little advice or encouragement on diet was available from dietitians, doctors or other health workers either prior to or after discharge. PMID- 4019256 TI - Footnotes to food tables: 1. Differences in nutrient intakes of dietitians as calculated from the DHSS food tables and the fourth edition of McCance and Widdowson's 'The composition of foods'. AB - The differences in nutrient intakes as calculated by two British food composition tables (those compiled by the Department of Health and Social Security in 1963 [DHSS] and the 4th edition of McCance and Widdowson's 'The composition of Foods' [MW4] were examined. Intakes of 43 dietitians who kept weighed diet records every sixth day for 3 to 12 months with 11 to 75 (mean 40) days' records per subject were calculated from each food table and compared in a loge tranformation. Mean per cent differences between intakes (delta x 100) were vitamin A, +23.3; vitamin D, + 21.1; riboflavin, + 16.0;calcium, +6.3; thiamin +4.8; niacin, +3.2 (MW4 higher) and protein, -1.7; fat, -3.5; energy, -3.6; carbohydrate, -6.0; vitamin C, -6.1; iron, -11.3; vitamin B6, -14.4 (MW4 lower). Correlation coefficients were: nicotinic acid, 0.84; vitamin B6, 0.86; other nutrients 0.90 to 0.99; thus differences between the two food tables in classifying individuals as high or low consumers were small. Mean intakes compared by paired t-test were significantly different (P less than 0.001) for all nutrients except nicotinic acid, indicating consistent differences in the food tables when applied to foods eaten by different individuals (nicotinic acid excepted). Mean intakes compared by one tailed t-test -- as if the data came from independent surveys -- were significantly different/only for riboflavin/and vitamin/B6 (P less than 0.01), vitamin A and iron (P less than 0.05). For these nutrients, significant differences in intakes could be found between two surveyed populations due solely to the use of different food tables and not to differences in foods eaten. For the other nutrients studied, differences between the food tables were of little practical importance. Differences were due primarily to new analytical values in MW4 for riboflavin in milk, retinol in liver, iron in meats, vitamin B6 in many foods, and the use of margarine fortified with vitamins A and D in recipes. Major differences in the (high) nicotinic acid content of beer, instant coffee and specific breakfast cereals resulted in unpredictable differences in intakes of individuals. PMID- 4019257 TI - Haematologic response of anaemic preschool children to ascorbic acid supplementation. AB - Fifty-four anaemic preschool children, all consuming similar, purely vegetarian, diets were randomly divided equally into an experimental and a control group. The children in the experimental group received 100 mg ascorbic acid twice a day, with lunch and with dinner, for 60 days. The controls received sugar placebos. Initially and at the end of the intervention, haemoglobin (Hb) and red cell morphology were estimated in all children. The children who received ascorbic acid supplements showed a significant improvement in Hb level as well as in red cell morphology, while the controls showed no change. Chemical analysis of the diets of a subsample showed ascorbic acid intakes to be very low. PMID- 4019258 TI - Nutritional status, energy and protein intake in general medical patients in three Nordic hospitals. AB - The energy and protein intake before and during hospitalization was studied in 56 elderly patients (age 70 +/- 9 yr) admitted to general medical service in three Nordic hospitals. Nutritional status at admission was evaluated using weight index, arm muscle circumference, triceps skinfold, serum albumin, total iron binding capacity, haemoglobin and serum iron levels. A history of food intake before hospitalization was taken at admission. Food intake during hospital stay was estimated from precise weighing and recording and intake of energy and protein calculated. On admission, 16 patients (28.5 per cent) had three or more of the studied nutritional parameters below reference value. Mean energy intake for men at home and in hospital was 10.0 +/- 2.3 MJ/d and 7.1 +/- 1.3 MJ/d, respectively, and for women 7.8 +/- 1.7 MJ/d and 6.6 +/- 1.4 MJ/d, respectively. Mean protein intake for men at home and in hospital was 72 +/- 19 g/d and 74 +/- 15 g/d, respectively, and for women 60 +/- 15 g/d and 68 +/- 13 g/d, respectively. In patients with a hospital stay exceeding two weeks a correlation between changes in body weight and energy intake was found. Likelihood of developing undernutrition during hospitalization, defined as a daily energy intake below 90 kJ/kg BW per day, was seen in 20 patients (36 per cent). The data obtained indicate that at least 120 kJ/kg should be regarded as necessary to maintain body weight in elderly general medical patients. It reveals the importance of regular nutritional assessment of these patients. PMID- 4019259 TI - Relationship between weight reduction and state of malabsorption after jejunoileal bypass for excessive obesity. AB - A 10-year follow-up study of 30 patients subjected to jejunoileal bypass surgery for obesity is reported. The technique used which resulted in a jejunoileal shunt length of 50-55 cm gave satisfactory weight reduction in 75 per cent of the patients. There were no serious complications. The weight loss occurred essentially during the first 12-18 months, the main cause being defective digestion and malabsorption. In some instances this was supported by initially reduced food consumption. A certain degree of steatorrhoea persists in most cases after 10 years and may be of importance in the maintenance of the new stable weight level. PMID- 4019260 TI - Creatinine excretion over 24 hours as a measure of body composition or of completeness of urine collection. AB - Continuous collections of urine for up to 3 weeks from obese patients on a meat free low-energy diet showed fluctuations in creatinine excretion so that the coefficient of variation was 8.7-34.4 per cent. Urine creatinine excretion was poorly correlated with measures of lean body mass such as density, body water or body potassium. Under the conditions of our study creatinine excretion is not a reliable indicator of either lean body mass nor the completeness of urine collection. We also conclude that the increased lean body mass in obese women contains a relatively small proportion of muscle. PMID- 4019261 TI - A simple fluorimetric assay for pyridoxamine phosphate oxidase in erythrocyte haemolysates: effects of riboflavin supplementation and of glucose 6-phosphate dehydrogenase deficiency. AB - The formation of pyridoxal and its phosphate from pyridoxamine phosphate by red cell haemolysates was measured in a centrifugal analyser by the formation of the fluorescent adduct with semicarbazide. Pyridoxal phosphate was found to react more rapidly than pyridoxal, thus permitting a distinction between the two products, and hence the measurement of phosphatase activity. Activity of the enzyme, pyridoxamine phosphate:oxygen oxidoreductase (deaminating) EC 1.4.3.5 (PPO) was measured in haemolysates from 72 Gambian women with evidence of riboflavin deficiency, and was repeated after 6 weeks of placebo or riboflavin supplementation. Those who received the riboflavin supplement responded with a marked increase in PPO activity, which was matched by a decrease in the activation coefficient (AC) of erythrocyte NAD(P)H2:glutathione oxidoreductase, EC 1.6.4.2 (glutathione reductase, EGR). No difference between the supplemented and unsupplemented groups was observed in the capacity of haemolysates to hydrolyse pyridoxal 5-phosphate, nor in the extent of activation of erythrocyte L aspartate:2-oxoglutarate aminotransferase EC 2.6.1.1. by pyridoxal phosphate. Although the three subjects with low levels of D-glucose 6-phosphate: NADP 1 oxidoreductase EC 1.1.1.49 (G6P-D) had, as expected, correspondingly low AC's of EGR, their unsupplemented activities of PPO were in the same low range as those of the G6P-D-normal subjects, and they responded as G6P-D-normal subjects did to riboflavin supplementation. PPO thus does not appear to resemble EGR in retaining its flavin coenzyme during riboflavin depletion.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4019263 TI - Aetiological factors of obesity in children. AB - A survey was carried out of the prevalence of obesity in 7600 schoolchildren aged 11-16 years in Cairo. Weight, height and skinfold thicknesses were measured and the children classified as underweight, normal or overweight. Overweight children were further screened for obesity, a triceps skinfold thickness of greater than 18 mm for boys and greater than 25 mm for girls being taken as the lower level of obesity. Age at menarche, birth order, social class, obesity in other members of the family, food habits and dietary intakes were all studied. The prevalence of obesity in Egyptian children was comparable to that in the US. The study emphasizes the importance of social and cultural influences in the development of obesity in Egyptian children. PMID- 4019262 TI - Haematological response to supplements of iron and riboflavin to pregnant and lactating women in rural Gambia. AB - Eighty-one pregnant or lactating women living in a village in The Gambia were allocated to treatment groups to receive a daily placebo, riboflavin, ferrous sulphate or ferrous sulphate plus riboflavin. At the beginning of the study and at 3 and 6 weeks thereafter women were examined clinically and blood samples collected for haematological and biochemical measurements. Pregnant women showed a wide range of response to supplement but among the lactating women an interesting pattern emerged: whereas the haematological status of the placebo group declined over 6 weeks, in the group receiving iron supplements this deterioration was reduced although not significantly. Riboflavin given in addition to iron resulted in a significant increase in circulating plasma iron and in iron stores, relative to the placebo. PMID- 4019264 TI - Incidence of biochemical riboflavin deficiency in Nigerian pregnant women. AB - The riboflavin status of 25 primigravidae and 55 multigravidae was determined by the erythrocyte glutathione reductase activation test during their first attendance at the antenatal clinic. Fifteen of the women (5 primigravidae and 10 multigravidae) were in the second trimester and 65 in the third trimester of pregnancy (20 primigravidae and 45 multigravidae). Fifteen of the primigravidae (60 per cent) and 44 per cent (24/55) of the multigravidae had an activity coefficient (EGR-AC greater than 1.30) indicative of biochemical riboflavin deficiency. The incidence of riboflavin deficiency among all women in the second trimester of pregnancy was 40 per cent (6/15), and 51 per cent (33/65) for all women in the third trimester of pregnancy. However, no clinical signs accompanied the biochemical deficiency of riboflavin. Riboflavin nutriture was slightly better in the multigravidae than in the primigravidae. The mean EGR-AC was 1.32 for the primigravidae and 1.26 for the multigravidae. The continual use of multivitamins in pregnancy and lactation should be strongly advocated. PMID- 4019265 TI - Efficiency of anthropometric indicators in the assessment of protein nutrition in Crohn's disease. AB - A comparison was made of the efficiency of different anthropometric indicators in assessing serum albumin and prealbumin concentrations in 60 adult patients with Crohn's disease. Indicators included weight, mid-arm circumference and triceps skinfold thickness at different cut-off points of reference (Jelliffe, 1966) and at the 5th percentile. Mid-arm circumference at 90 per cent reference gave the most significant separation of serum albumin and prealbumin, and protein concentrations in patients whose mid-arm circumference was at or above 90 per cent reference approached most closely the values obtained in healthy subjects. Mid-arm circumference is a simple and reproducible measurement, and the results support the suggestion that it is a useful indicator for assessing protein nutrition in Crohn's disease. PMID- 4019266 TI - A comparison of two methods of milk sampling for calculating the fat intake of breast-fed babies. AB - Fat intake at a breast feed was estimated by either sampling milk intermittently during the feed using a thin latex nipple shield ('shield method') or by expressing samples before and after the feed ('expression method'). These sampling techniques were compared within 30 mother/infant pairs using a randomized cross-over design. Mean fat intake estimated by the expression method was significantly greater than that estimated by the shield method (first breast P less than 0.0001, second breast P less than 0.002). This finding was partly explained by a significantly lower mean milk intake when the nipple shield was used, but the higher fat content of expressed milk samples compared to samples obtained during suckling also played a part. Use of the nipple shield confirmed that breast-milk fat content does not change in a predictable way during a feed. Nevertheless, for practical purposes, the advantages of studying changes in milk composition during the feed have to be set against the potential restrictive effect of the nipple shield system when it is used to sample intermittently during the feed. PMID- 4019267 TI - Effect of ascorbic acid supplementation on selenium bioavailability in humans. AB - The study was designed to investigate the effect of supplemental ascorbic acid on the bioavailability of selenium (Se) in humans by using plasma Se levels and plasma glutathione peroxidase (GSH-Px) activity as indicators of the body Se status. Three groups of female university students were supplemented for 4 weeks with either 50 micrograms sodium selenate, 50 micrograms sodium selenate together with 200 mg ascorbic acid, or with 200 mg ascorbic acid three times daily during meals. Plasma Se levels increased significantly (P less than 0.01) in all three groups regardless of the type of supplementation. The increase was highest in the group having both Se and ascorbic acid and smallest in the group receiving only ascorbic acid. The changes in plasma GSH-Px activities reflected those in plasma Se, but the increases were smaller (P less than 0.05). These results suggest that supplemental ascorbic acid may have a beneficial effect on the bioavailability of the natural Se in foods. However, ascorbic acid did not seem to affect the availability of the supplemental sodium selenate. Therefore, the effect of ascorbic acid on the bioavailability of selenium may vary depending on the ingested selenium compound. PMID- 4019268 TI - Blood ascorbic acid and histamine levels in patients with placental bleeding. AB - Concentrations of histamine and total ascorbic acid (L-ascorbic acid plus dehydroascorbic acid) in the antecubital vein blood of women in abruptio placentae (normally situated placentae) and placenta praevia have been measured. The results show that blood ascorbic acid in abruptio placentae is significantly (P less than 0.05) lower than the values found in placenta praevia. This may reflect impaired absorption and/or increased breakdown of ascorbic acid in abruptio placentae. Histamine levels in the two conditions are similar to one another. PMID- 4019269 TI - The influence of excisional or incisional biopsy of metastatic neck nodes on the management of head and neck cancer. AB - Between November 1964 and December 1981, 80 patients who had undergone an open biopsy of a cervical lymph node containing squamous cell carcinoma were treated with curative intent in the University of Florida Division of Radiation Therapy. Irradiation was the initial step in the definitive treatment of all patients, followed by neck dissection and/or primary resection, as indicated. The patients were divided into two groups. (a) NX (no gross residual neck disease) (25 patients): According to the referring surgeons' and pathologists' reports, a single, clinically positive lymph node was totally excised in 25 patients. No other clinically positive lymph nodes were appreciated upon referral. No neck dissections were added following irradiation in this group of patients. The absolute 5 year disease-free survival in the NX group was 79%, and the rate of neck disease control was 96%. (b) Gross residual neck disease (55 patients): Gross residual disease remained in the neck in 55 patients following biopsy. In some patients, only an incisional biopsy of a large mass had been performed; in others, only one of several involved nodes was removed. The absolute 5 year disease-free survival in this group of patients was 31%, and the rate of neck disease control was 64%. The more consistent addition of a neck dissection in recent years has resulted in improved neck control rates in this group: 13/20 (65%) for N1-N2 disease and 2/7 (29%) for N3A disease following irradiation alone versus 6/7 (86%) for N2 disease and 5/8 (63%) for N3A disease when a neck dissection was added following irradiation. There are some differences in the rates of neck control, control above the clavicles, survival, distant metastasis, and complications between this series and other reported series in which open neck-node biopsy preceded definitive treatment. Possible reasons for these differences are discussed. PMID- 4019270 TI - The role of paraaortic node irradiation in the treatment of cancer of the cervix. AB - One hundred and twenty-seven patients with previously untreated carcinoma of the uterine cervix underwent pretreatment laparotomy between 1971 and 1980. Thirty one were found to have paraaortic metastasis. Twenty-seven patients received paraaortic node external supervoltage radiation to the entire paraaortic chain, 4400 cGy, over 4 1/2 weeks, with 600-800 cGy, boost over 1 week, limited to the area of metastasis as marked at laparotomy. Twenty-nine percent (8/27) of the patients with paraaortic node metastases who were irradiated have survived 5 years or more. These patients have FIGO stages IB, IIA, or IIB; all have epidermoid carcinoma. Three of five patients (60%) with microscopic metastasis and five of twenty-two patients (23%) with gross metastasis in the paraaortic lymph nodes are long-term survivors. None of our long-term survivors have suffered late complications. There have been no fatalities from treatment related complications. We present a radiation technique for paraaortic radiation in these patients, and discuss the indications for paraaortic node radiation in cancer of the cervix. PMID- 4019271 TI - Clinical trial of 252Cf neutron brachytherapy vs. conventional radiotherapy for advanced cervical cancer. AB - 252Cf, a neutron emitting radioactive transplutonium isotope, was tested for its efficacy against advanced bulky Stage III-IV cancers of the cervix in a clinical trial at the University of Kentucky Medical Center. Eighty-two patients were treated during 1976-1979 and followed for 5-year survival and tumor control. Three different treatment methods went on sequentially and concurrently, that is, (a) conventional whole pelvis photon with delayed 137Cs implants, (b) conventional photon therapy with delayed 252Cf implants, and (c) 252Cf implants ("early") preceding photon therapy. There were 12% 5-year survival for Stage IIIB cancers by conventional therapy, and 15% by delayed 252Cf implant therapy. For early 252Cf implant therapy there were 54% 5-year survivals with 4% complications and 65% 5-year local control, but distant metastases became a prominent delayed failure pattern. PMID- 4019272 TI - Combination of 60Co gamma-radiation, misonidazole, and maltose tetrapalmitate in the treatment of Dunning prostatic tumor in the rat. AB - Maltose tetrapalmitate (MTP), a synthetic nontoxic immunoadjuvant, the radiosensitizer misonidazole (MISO), and 60Co gamma-radiation, alone or in combination, were used in the management of Dunning prostatic tumor in the rat. Nine groups of 10 rats each were used to assess the efficacy of various therapeutic modalities. Tumor growth rates and animal survival times were determined for each group. Radiation was more effective when combined with MTP, but the adjuvant must be present when radiation is given for synergism to occur. MISO was as effective as MTP when used with radiation, but combining them cancels out their individual effects. In a clinical situation it would be advantageous to use separately the synergisms existing between MISO and radiation on the one hand and MTP and radiation on the other hand. PMID- 4019273 TI - The relationship between lung colony and in situ assays. AB - The relationship between three different assays: tumor control, tumor growth delay and lung colony formation, was examined after fast neutron and gamma ray irradiations. Fibrosarcomas (NFSa) in syngeneic C3Hf mice were irradiated locally with 60Co gamma rays, fast neutrons or mixed beams (gamma rays and fast neutrons). A comparison between the lung colony assay and the TRT50 (50% tumor growth delay time) assay when cells were exposed to single doses of fast neutrons or gamma rays, resulted in identical growth delay times. The fraction of cells surviving a single dose of fast neutrons, was 10 times higher than the surviving fraction of cells after a single dose of gamma rays. Both doses resulted in the same tumor control probability (TCD50 assay). Neither repair of potentially lethal damage nor tumor bed effect was sufficient to explain the difference between cell survival and tumor control probability. The surviving fraction of cells following fractionated irradiations of gamma rays and fast neutrons were identical at 50% tumor control probabilities. PMID- 4019274 TI - The effect of actinomycin D on radiation induced reactions of the lip mucosa of mice. AB - The interaction of intraperitoneally injected Actinomycin D and irradiation was investigated in the lip mucosa of NMRI mice. In this rapidly proliferating tissue, a semiquantitative assessment of possible modifications of the radiation response by a drug can be done without using lethality as an endpoint. It was shown that a single dose of 0.5 mg/kg drug given at different times between 24 hr prior to and 24 hr after single radiation doses did not effect the rate of development nor the intensity of mucosal radiation damage. With extended time intervals of 2, 3, or 7 days between both single agents, a slight increase of the lip mucosal reaction was measured. Similar results were obtained when 5 daily drug injections of 0.15 mg/kg were administered starting at day 5 after a single radiation exposure. No differences in response could be demonstrated when fractionated irradiations with intervals ranging from 1 to 24 hr were closely combined with either single or repeated drug treatments (0.5 mg/kg in total) as compared to irradiation alone. However, a slight modification of the iso-effect dose was measured when 0.5 mg/kg Actinomycin D was administered at various periods in between 2 radiation doses separated by 10 days. A maximal effect was measured with 5 daily injections of 0.15 mg/kg drug each and given at a time when proliferative capacity was high. With 0.1 mg/kg Actinomycin D per daily injection, no enhancement of the radiation injury was found. Thus, in these circumstances no influence of Actinomycin D on radiosensitivity nor on repair of sublethal damage could be demonstrated. A clear inhibitory effect on lip mucosal repopulation by the drug is evident, but only at high drug doses close to toxic concentrations. PMID- 4019276 TI - Strategies for treating possible tumor extension: some theoretical considerations. AB - When there is a small possibility of cancer having extended to a region some distance from the main bulk of disease, it may be unclear whether to include that region in the target volume and, if so, what dose should be delivered to it. We have constructed a theoretical model that includes dose and volume relationships for both diseased and normal tissue. With this model one can calculate the change in tumor control probability (TCP) when varying doses are delivered to the regions of known and suspected disease. Values of TCP as a function of dose to the region of suspected disease have been calculated for a wide range of the variables on which the model depends. We conclude that the strategy of treating the region of suspected disease to about 70% of the dose delivered to the region of known disease is almost always better than not treating it at all, or treating both regions to a uniform but reduced dose designed to keep the probability of complication the same. The gain in TCP could be from 5 to 15% for situations of clinical interest. PMID- 4019275 TI - Radiation-induced inhibition of thymidine incorporation in vivo as a measure of the initial slope and RBEn/gamma. AB - Radiation damage can be measured by decreased incorporation of 3H-TdR. The early effect of total body irradiation of mice, with doses up to 300-400 rad, of gamma rays of neutrons, on thymidine-3H incorporation into the DNA of murine proliferating normal and tumor cells are described. Total body irradiation with single doses up to 300 rad resulted in a steep dose-dependent depression of 3H TdR incorporation into the DNA of the jejunal crypt, testis, spleen, fibrosarcoma (FSa), and FSa metastasis cells. The dose required to depress 3H-TdR incorporation values to 37% of control level (D37/thymidine) after gamma irradiation was calculated to be 405, 443, 72, 303, and 531 rad, for jejunal crypt, testis, spleen, FSa metastasis, and FSa tumor cells, respectively. The depression progressed during the first 3 hours after irradiation. After neutron irradiation, the D37/thymidine was calculated to be 81, 140, 35, and 155 rad for jejunal crypt, testis, spleen, and FSa metastasis cells, respectively. The RBEn/gamma derived from these results were 5.00, 3.16, 2.06, and 1.95 for jejunal crypt, testis, spleen, and FSa metastasis cells, respectively. These results of D37/thymidine after gamma-irradiation and the RBEn/gamma correlate well with the 1Do for the initial slope of the survival curve and RBEn/gamma published in the literature for C3H/Kam mice using the same gamma and neutron beams. These findings show that cell survival after small doses of irradiation correlate with the effect of irradiation on the actively proliferating cells at the time of irradiation. PMID- 4019277 TI - Clinical experience with a computerized record and verify system. AB - To improve the quality of patient care by detecting and preventing many types of treatment mistakes, we have implemented a computerized system for recording and verifying external beam radiation treatments on our therapy machines. It inhibits the radiation beam if treatment machine settings do not agree with prescribed values to within maximum permissible deviations (tolerances). The tolerances are determined from experience and adjusted when necessary to make the system more effective and less susceptible to "false alarms." The system uses a common data base for all treatment machines. As a result, it permits statistical analysis and generation of reports based on data encompassing the entire patient population as well as verification of treatments of patients transferred from one machine to another. Reports of verification failures reveal patterns of mistakes. Knowing these, attempts can be made to reduce the frequency of verification failures. "Significant" mistakes that were prevented are extracted by treatment planning personnel from these reports. Analysis of data indicates a rate of approximately 150 "significant" mistakes detected and prevented per machine per year, representing 1.0% of all fields treated. We present and discuss our experiences with the system and with the frequency, patterns, and significance of verification failures. We selected a few of the patients for whose treatments significant set-up mistakes were made, and were detected and prevented by the Record and Verify System. We include discussions of the overall effect these mistakes would have had on dose distribution had they not been prevented. PMID- 4019278 TI - Obtaining local SAR and blood perfusion data from temperature measurements: steady state and transient techniques compared. AB - A series of analyses and experiments was performed to determine the extent that SAR and blood perfusion information can be extracted from steady state temperature values and from transient temperature measurements following a step change in applied power. Multiple local temperature measurements were made in canine thighs heated by 2450 MHZ microwaves to evaluate two parameters: the local absorbed power in the tissue, and the local "effective blood perfusion." The theoretical bases for these calculations are presented in order to identify their underlying assumptions and to obtain a unified basis for comparison of the various calculation methods used by previous investigators. From energy balance considerations it can be shown that the local absorbed power can be obtained from either the rate of increase of temperature following a step increase in power, or from the rate of decrease in temperature immediately following a step decrease in power. These theoretical observations are verified experimentally by comparing the SAR results at fixed positions in canine thighs as calculated from both increasing and decreasing power steps. For decreasing power steps, the resulting decreasing temperature curves can also be used to calculate an effective blood perfusion rate if thermal conduction is included. Alternatively, this same effective blood perfusion rate can be calculated from steady state data. (These two approaches have been used by previous investigators to determine "blood perfusion" values. We have added the modifier "effective" to specifically denote the presence of thermal conduction effects in such perfusion calculations.) From our experimental results and theoretical calculations it appears that differences between the predictions of the two calculation methods arise from changing thermal conduction values during the cooling period of the thermal clearance method. The steady state calculation approach is easier to apply than the washout method, but it requires the additional knowledge of the local SAR value. It is important to realize that effective blood perfusion values calculated using thermal techniques are subject to large errors under conditions where thermal conduction is important, unless this conduction is explicitLy included in the calculation. Such effective blood perfusion values should not be quantitatively compared to values calculated from non-thermal techniques that are not affected by thermal conduction. Unless such conduction effects are known to be negligible, effective perfusion values are only qualitative indicators of the presence of changes in blood perfusion. PMID- 4019279 TI - Test of recurrence after experimental radiation therapy of chemically induced autochthonous tumors in mosaic mice. AB - True recurrence was distinguished from induction of new second tumors after experimental radiation therapy using monoclonal tumors produced in the mosaic cell background of mice. The mice were C3H/He females heterozygous at the X chromosome-linked locus of phosphoglycerate kinase (PGK) and consisted of two types (A and B) of somatic cells by inactivation of one of X-chromosomes. Sarcomas and carcinomas with a single PGK phenotype were produced by subcutaneous injection of 3-methylcholanthrene (MCA) into the groin of the mice, and locally and singly irradiated with 4-6.5 Krad of X rays generated by a 6 Mev linear accelerator, when they were 8-10 mm in diameter. Of 69 mice irradiated, 17 were available for comparison of the PGK and histological types of primary and recurrent tumors. Of these, 10 recurrent tumors with A-type PGK and 3 with B-type PGK exhibited the same PGK type as that of primary tumors, while one was distinguishable histologically. Only one recurrent tumor was of the opposite PGK and a different histological type from the primary tumor. Considering the probability of new tumor formation among A----A recurrent tumors, it was calculated that 79% (11/14) of the tumors that reappeared in the irradiated area were actually true recurrent tumors. Autochthonous tumors may be important in testing therapeutic methods. PMID- 4019280 TI - Benefit, risk, and optimization by ROC analysis in cancer radiotherapy. AB - The objective of definitive cancer radiation therapy is cure or control. The attainment of that objective is not without risk of treatment-induced radiation injury. The optimum treatment is, therefore, that level of radiotherapeutic effect with the maximum probability of benefit and the minimum associated probability of injury. An objective of radiotherapy research is the formulation of a model of optimization that is independent of a consensus of what constitutes optimization. Receiver operating characteristic (ROC) analysis is such a model, for it can relate probabilities of benefit and injury yielding a graphical determination of the optimum level of radiotherapeutic effect. ROC analysis is explained, an example taken from the contemporary radiotherapy literature is presented, and clinical research requirements for a general application of ROC analysis to the optimization of definitive cancer radiotherapy are developed. PMID- 4019281 TI - Evaluating cancer patients for metastases: an approach using Bayes' theorem. AB - Before patients with apparently localized cancer are offered potentially curative surgery or radiation therapy, physicians often order a battery of imaging studies to exclude metastases. The yield of radionuclide liver and bone scans and computed tomography of the brain in breast, colorectal, and lung carcinomas was examined as follows: the literature was reviewed to obtain the autopsy prevalences of brain, liver and bone metastases in breast, colorectal and all histologies of lung carcinoma, to estimate the sensitivities and specificities of radionuclide liver and bone scans and computed tomography of the brain. Using Bayes' theorem, the predictive accuracies of positive and negative clinical evaluations and imaging studies were computed. For most of the examples analyzed, the imaging studies do not provide information beyond that obtained by the history, physical examination, and inexpensive laboratory tests and radiographs that would alter the physician's decision to offer curative treatment directed towards local disease. This method is presented as a model for clinical decision making where the information gained by an additional study is evaluated for its use in altering therapeutic decisions. PMID- 4019282 TI - Inappropriate use of linear-quadratic analysis of tumor response. PMID- 4019283 TI - Proceedings of the American Society for Therapeutic Radiology and Oncology, 27th annual meeting. September 29-October 4, 1985, Miami Beach, Florida. Abstracts. PMID- 4019284 TI - Taenia saginata cysticercosis in an Ohio cattle feeding operation. AB - In January to March 1981, 37 slaughter cattle from a single Ohio feeding operation were determined, at postmortem inspection, to be infected with Taenia saginata cysticerci. A subsequent outbreak on this same farm in March 1983 involved 7 slaughter cattle. An epidemiologic investigation was conducted of possible sources of the T saginata ova; these included leakage of raw sewage onto the pasture after a flood in 1980, municipal sewage sludge application on the farm, defecation in feed or water by farm workers, and other off-farm sources. Temporal and spatial observations implicated raw sewage contamination of pastures as the most likely source of infection in the 1981 outbreak. The outbreak in 1983 was more likely associated with sludge application. The possibility of an infected worker exposing the cattle to infected feces was not excluded definitely as a possible source. PMID- 4019286 TI - Effect of unilateral orchiectomy on semen quality in bulls. AB - Unilateral orchiectomy was performed on 9 mature mixed-breed bulls with satisfactory semen quality to study the effect of the procedure on quality of semen from the contralateral testicle. Semen was collected by electroejaculation before surgery and on alternate days for 2 weeks, then once weekly for 8 weeks. Each sampling day, progressive motility and morphologic features of spermatozoa were determined, and scrotal thermograms were taken. The percentage of normal spermatozoa decreased significantly (P less than 0.05) only on postoperative day 6. Progressive motility scores varied but at the end of the study there was no significant difference from preoperative values. Scrotal thermography revealed inflammation in the contralateral side of the scrotum, beginning 3 days after surgery, but the thermograms were normal in most bulls by 3 weeks after surgery, and all thermograms were normal by 4 weeks. PMID- 4019285 TI - A correlative study of the clinical and radiographic signs of periodontal disease in dogs. AB - Twenty-four dogs admitted for routine teeth cleaning were selected arbitrarily to undergo a periodontal examination and a dental radiographic examination before the dental procedure. Data pertaining to the physical and radiographic manifestations of periodontal disease of 783 teeth were collected. All dogs had lesions consistent with periodontal disease, ranging from mild gingivitis and minimal plaque accumulation to severely inflamed gingiva, exuberant calculus formation, and root exposure. Of the 783 teeth examined, 153 (20%) had a pocket depth greater than or equal to 4 mm and less than or equal to 9 mm. Data regarding these teeth were subjected to statistical analysis. The clinical signs of plaque, calculus, mobility, pocket depth, and furcation were positively associated with radiographic signs of periodonta disease. The association between grossly evident gingivitis and radiographic signs of periodontal disease was not significant. Conditional probability analysis was applied to determine confidence intervals for the probability of a radiographic sign of periodontal disease occurring given that a clinical sign of periodontal disease occurs. PMID- 4019287 TI - Neoplasia of the equine urinary bladder as a cause of hematuria. AB - In 6 horses with urinary bladder neoplasms, common clinical findings included a palpable mass in the bladder, anemia, hematuria, and/or proteinuria. Squamous cell carcinoma was found in 4 horses and appears to be the most common bladder tumor in the horse. Single cases of transitional cell carcinoma and fibromatous polyp also were identified. All horses except one were over 10 years of age. In one mare, treatment with 5-fluorouracil intracystically resulted in decreased bleeding from the bladder mass and apparent stabilization of the mass size. The mare ultimately died because of abdominal metastasis. Although rare, neoplasia of the urinary bladder should be considered when evaluating horses with hematuria. PMID- 4019288 TI - Vagus indigestion syndrome resulting from a liver abscess in dairy cows. AB - A liver abscess resulted in vagal indigestion in 8 dairy cattle. There was cessation of transport of digesta through the omasum. Clinical signs were of variable duration and included abdominal distention and bradycardia. Medical therapy had not been effective. Left paralumbar fossa celiotomy and rumenotomy permitted detection of the liver abscess. A second surgery from a ventral approach allowed drainage of the abscess by insertion of a catheter through the abdominal wall. PMID- 4019289 TI - Effects of enterocentesis on peritoneal fluid constituents in the horse. AB - Peritoneal fluid was collected from 15 clinically normal horses and was analyzed for nucleated cell (NC) counts and specific gravity. Six horses (controls, group 1) were subjected to abdominocentesis only, with a teat cannula, every 24 hours for 5 days. There were no marked changes in the peritoneal fluid of these horses over the 5-day period. Peritoneal fluid was collected from 6 other horses (group 2) with an 8.89-cm 18-gauge needle. The needle was then advanced until intestinal fluid was obtained. Peritoneal fluid was then collected with teat cannulas at 24 hour intervals for an additional 4 days. Peritoneal fluid NC counts from group 2 horses were significantly increased (P less than 0.05) at peak values 2 days after enterocentesis. Specific gravities of peritoneal fluid from group 2 horses were increased on days 1 and 2 after enterocentesis (P greater than 0.05). Peritoneal fluid from 3 other horses (group 3) was collected before enterocentesis (base line) and again at 4-hour intervals after enterocentesis. Peritoneal fluid NC counts of group 3 horses were markedly increased above base line values 4 hours after enterocentesis and continued to increase for up to 12 hours after enterocentesis when the experiment was terminated. All horses that underwent enterocentesis remained clinically normal except 1 group 3 horse that had a fever (39.6 C) 24 hours after enterocentesis. PMID- 4019290 TI - Intestinal decompression: preliminary study in the horse. AB - A technique of nasoduodenal (N-D) intubation and intestinal decompression was developed and used in the horse to explore the prevention of gastric and intestinal distention after abdominal surgical operation. Three styles of tubes (2 single-lumen tubes and 1 double-lumen tube) were positioned in the duodenum of 12 mature horses (10 experimental and 2 clinical) during laparotomy (without enterotomy), and an iatrogenic occlusion at the small intestine was created and later released in the 10 experimental horses. The 2 clinical horses had an exploratory laparotomy to correct a natural obstruction of the small intestine. After each horse recovered from surgical manipulation, suction was used to keep fluids from accumulating in the cranial part of the gastrointestinal tract. In 5 of the 12 horses, the most simple N-D tube was positioned successfully and functioned properly. Three of the 5 horses which were fasted before surgical manipulation (to obtain an empty stomach) survived without postsurgical complications. Volume of reflux material was measured. Clinical data, such as periods of comfort during decompression without giving analgesics, were recorded. Necropsies were done on 10 of the 12 horses (9 experimental and 1 clinical). Although already tested in 2 clinical horses, use of the N-D tube remains experimental, and the N-D tube functioned only in horses which were fasted before surgical manipulation. Perfection of a safe and dependable means of emptying the equine stomach of its solid ingesta before gastrointestinal intubation is done, is the next step in affording greater clinical application of the N-D tube for gastrointestinal decompression. PMID- 4019291 TI - Ruptured urinary bladder in a heifer. AB - A yearling Holstein heifer was admitted with abdominal pain and bilateral, ventral abdominal distention. Bladder rupture was diagnosed by abdominocentesis and endoscopy. Correction of metabolic derangements was accomplished by volume diuresis, with maintenance of a urethral catheter before surgical repair of the bladder. The cause of the bladder rupture was believed to be related to adhesions resulting from previous surgery for urachal abscessation. Bladder rupture, which usually occurs in bulls or steers secondary to urolithiasis or in cows after dystocia, also should be considered in prepartum heifers with dehydration, abdominal pain, and abdominal distention. PMID- 4019292 TI - Pharyngeal polyps in two feline siblings. AB - Pharyngeal polyps were diagnosed in 2 sibling kittens referred for evaluation of chronic upper respiratory tract disease. Surgical excision of the masses was performed in both kittens after skull radiography and oral examination. One kitten had a recurrence of pharyngeal polyps 5 weeks after surgery and was euthanatized and necropsied. The clinical and histologic findings in these 2 cases suggested a congenital origin of this disease. PMID- 4019293 TI - Suspected immune-mediated megakaryocytic hypoplasia or aplasia in a dog. AB - Megakaryocytic hypoplasia or aplasia causing thrombocytopenia was diagnosed in a 3-year-old Miniature Poodle with scleral hemorrhage, melena, ecchymoses, and blood-loss anemia. Immunosuppressive, cytotoxic, and lithium carbonate therapy resulted in successful correction of the dog's disease. It is important to recognize megakaryocytic hypoplasia or aplasia as the cause of thrombocytopenia, since the response to therapy will be slower when there is stem cell injury. PMID- 4019294 TI - Segmental hemiatrophy in a dog. AB - Congenital asymmetric development, resulting in a small right thoracic limb, was diagnosed in a dog. The limb was anatomically normal. The lesion closely resembled hemiatrophy. Congenital asymmetric development should be considered in the differential diagnosis of limb length discrepancies. Treatment is required only in cases of extreme discrepancy between the normal and affected limb. PMID- 4019295 TI - Choledocholithotripsy in a mare. AB - Obstructive choledocholithiasis in a 12-year-old mare was corrected surgically by choledocholithotripsy. The mare had a history of chronic weight loss, intermittent fever, partial anorexia, jaundice, recurrent abdominal pain, and an abdominal mass palpable per rectum. Values for alkaline phosphatase, bilirubin, gamma-glutamyl transferase, sorbitol dehydrogenase, and bromsulpthalein half-life were increased and bilirubinuria was evident before surgery. Two liver biopsies revealed periportal and portal fibrosis, bile duct proliferation, cholestasis, and variable amounts of hepatocellular necrosis, with infiltration by polymorphonuclear cells. Immediate clinical improvement was seen after surgery, and results of selected liver function tests gradually returned to normal. Since surgery, the mare has returned to her normal weight, has remained clinically normal for liver disease for 28 months, and has been useful as a broodmare. PMID- 4019296 TI - Use of 111In-labeled autologous leukocytes to image an abdominal abscess in a horse. AB - Indium 111-labeled autologous leukocytes were used to image an abdominal abscess in a horse with a palpable abdominal mass and history of Streptococcus equi infection. A focal area of radioactivity was identified in the location corresponding to the abscess. Imaging of this focal uptake was optimal 48 hours after injection. Similar scans obtained in 2 clinically normal horses revealed no evidence of focal radioactivity in this region. The cell labeling procedure gave acceptable labeling efficiency (87.5%) but an excessive number of damaged WBC, resulting in persistent lung radioactivity on all images. No adverse effects were noted. Radiation measured in the horse and its excreta were well within acceptable limits. PMID- 4019297 TI - Hemodialysis of a dog with acute renal failure. AB - A dog with oliguric acute renal failure presumed to have been caused by ethylene glycol ingestion was treated by hemodialysis for 1 month. Hemodialysis was effective in controlling azotemia, hyperphosphatemia, and hyperkalemia when performed on a daily or alternate-day basis. The major complications during treatment were infection and severe weight loss. Serial renal biopsies disclosed a progression from initial acute tubular necrosis to severe diffuse interstitial fibrosis and mononuclear cell inflammation. Infection, cachexia, development of end-stage renal lesions, and terminal hyperkalemia contributed to the eventual death of the dog. PMID- 4019298 TI - Clinical evaluation of dogs after surgical and nonsurgical management of osteochondritis dissecans of the talus. AB - Osteochondritis dissecans of the medial aspect of the talus was diagnosed in 17 joints in 11 dogs. In 10 of the 11 dogs, intermittent lameness had persisted after initial diagnosis and therapy. Radiographs made during the initial examination showed a widening of the medial tarsocrural joint space, with osteophyte formation involving the medial and caudal tarsocrural joint. The follow-up radiographs showed greatest change in the increase in reactive bone formation, especially involving the medial and caudal aspects of the tarsocrural joint and the medial aspect of the talus. Arthrotomy for flap removal and curettage was performed on 11 joints; 6 joints did not receive surgery. After a mean period of 34 months following diagnosis, the dogs were examined clinically and the affected joints were radiographed. The degree of lameness, range of motion, and stability of the tarsocrural joint were graded for each limb. Radiographic determinants that were assessed included: width of the medial tarsocrural joint space, medial tarsocrural osteophyte formation, lateral tarsocrural osteophyte formation, caudal tarsocrural osteophyte formation, medial talus osteophyte formation, lateral talus osteophyte formation, intertarsal osteophyte formation, subchondral sclerosis of the distal end of the tibia, presence of joint bodies, and periarticular soft-tissue thickness. On the basis of clinical and radiographic evaluations, the surgical procedures described in this report did not modify progression of osteoarthritic changes. PMID- 4019299 TI - Occipitoatlantoaxial malformation in two non-Arabian horses. AB - Occipitoatlantoaxial malformation was diagnosed in a 19-month-old mare of Appaloosa breeding and in a 3-year-old Quarter Horse gelding. Both horses had abnormal head and neck carriage since birth, but neurologic deficits did not become evident clinically until the horses reached 2 and 3 years of age, respectively. Palpation and manipulation of the base of the skull and cervical area proved to be useful diagnostically. Movement could not be elicited at the atlantooccipital joint but, in comparison with clinically normal horses, the range of dorsoventral motion at the atlantoaxial joint was increased. Alternate subluxation and relocation of this joint generated audible clicking sounds. Radiography revealed symmetric atlantooccipital fusion, with modification of the atlas, atlantoaxial joint, and axis. These findings were confirmed at necropsy. PMID- 4019300 TI - Treatment of cyclophosphamide-induced cystitis. PMID- 4019301 TI - Bone marrow necrosis in the dog. AB - Bone marrow necrosis in 4 dogs was characterized by refractory anemia with or without leukopenia and thrombocytopenia. Romanovsky-stained bone marrow had a diffuse blue discoloration, and marrow particles were elongated. Degenerating cells, cellular debris, and vacuolated macrophages also were seen. Examination of bone marrow sections revealed extensive replacement of normal stroma by necrotic debris and hemorrhage. The cause of the necrosis was not determined. Concomitant disorders included chronic ehrlichiosis, estrogen toxicosis, malignancy, endometrial cystic hyperplasia, and glomerulonephritis. PMID- 4019302 TI - Tracheal rupture in two horses. AB - Two horses were admitted for evaluation of diffuse SC emphysema. Diagnosis of ruptured trachea was made by tracheoscopy and radiography. The tracheal cartilages were not involved in either case. One of the defects was small and responded to medical management. The other defect was large and was apposed surgically. Both horses recovered without complications. PMID- 4019303 TI - Pseudohyperchloremia associated with bromide intoxication in a goat herd. AB - Pseudohyperchloremia and a negative anion gap were detected in goats with bromide intoxication. Bromide interferes with ion-specific electrodes, resulting in a falsely increased serum chloride concentrations. Bromide intoxication should be considered in animals with progressive neurologic signs, a high serum chloride value, and a low or negative anion gap. PMID- 4019304 TI - Fracture of the greater tubercle of the humerus in a filly. AB - A fracture of the caudal portion of the greater tubercle of the humerus was diagnosed in a 16-month-old Thoroughbred filly. Initially the fracture caused severe lameness. Radiography of the affected shoulder revealed the fracture fragment to be extra-articular, with a surrounding bony callus and no evidence of joint disease. After 5 weeks rest in a stall and 11 months at pasture, the filly was trained and raced without lameness. PMID- 4019305 TI - Paragonimiasis in a dog: treatment with praziquantel. AB - Oral administration of 25 mg of praziquantel/kg of body weight 3 times a day for 2 consecutive days resulted in clinical and parasitologic cure of paragonimiasis in a dog. Previous treatment with the drug at the dosage recommended for cestode removal (5 mg/kg, SC) for 2 days was only partially effective. The dog exhibited cachexia, coughing, gagging, and occasional hemoptysis. Radiography revealed nodular and cystic densities in the lungs. The life history and clinical aspects of Paragonimus kellicotti infection in the dog are briefly reviewed. PMID- 4019306 TI - Tetraparesis following cervical disk fenestration in two dogs. AB - Two dogs were nonambulatory and tetraparetic following cervical disk fenestration used as the treatment for cervical disk disease. Severe pain and cervical muscle fasiculation also were evident. The site of disk extrusion was localized radiographically, and cervical ventral decompression was used to remove the disk material. Recovery in both cases was complete. PMID- 4019307 TI - Aridicins, novel glycopeptide antibiotics. I. Taxonomy, production and biological activity. AB - A new species of a new genus of the Actinomycetales was discovered, Kibdelosporangium aridum. This strain produces a new family of glycopeptide antibiotics designated aridicins, that contain an unusual glycolipid constituent. They inhibit Gram-positive bacteria, including staphylococci, enterococci and Clostridium sp. PMID- 4019308 TI - Aridicins, novel glycopeptide antibiotics. II. Isolation and characterization. AB - A new antibacterial antibiotic complex, aridicin, was produced by a new genus, Kibdelosporangium aridum (SK&F-AAD-216). The individual factors, aridicins A, B and C, were isolated from the fermentation broth by an Amberlite XAD-7 resin extraction and purified by preparative reversed phase HPLC. The aridicins were found to be novel members of the glycopeptide class of antibiotics as exemplified by ristocetin and vancomycin, based on chemical and spectroscopic data, their molecular weights as determined by FAB mass spectrometry (1,786, 1,800 and 1,814), the detection of actinoidinic acid in their acid hydrolysates, and detailed TLC and HPLC comparisons with representative members of this class. PMID- 4019309 TI - The structure of A201A, a novel nucleoside antibiotic. AB - The structure of the novel nucleoside antibiotic A201A has been determined by a combination of chemical and spectroscopic methods. It is composed of 6 dimethylaminopurine, 3-amino-3-deoxyribose, p-hydroxy-alpha-methylcinnamic acid, a novel unsaturated hexofuranose and 3,4-di-O-methylrhamnose. Structures have also been assigned to several related minor factors simultaneously isolated from the fermentation broth. These unique nucleosides have very interesting similarities and differences in structure with the known antibiotics puromycin and hygromycin A. PMID- 4019310 TI - Synthesis of several new carbapenem antibiotics. AB - A synthesis of several carbapenem antibiotics including 9-methoxythienamycin is described. The final deprotection of C-3 esters was accomplished by a novel procedure using aluminum trichloride under a very mild condition. The antibacterial activity against Gram-positive and Gram-negative bacteria is shown. PMID- 4019311 TI - Studies on the biosynthesis of carbapenem antibiotics. III. Enzymological characterization of the L-amino acid acylase activity of A933 acylase. AB - A933 acylase, which is involved in exchange of the pantothenyl substituent of OA 6129 carbapenems with acetyl CoA, was characterized as an L-amino acid acylase with a molecular weight of 100,000 (+/- 8,000) and a pI value of 5.1. The highest L-amino acid acylase activity of A933 acylase was observed at 37 degrees C and pH 7 approximately 7.5 for N-chloroacetyl-L-phenylalanine. Unlike other amino acid acylases, A933 acylase was severely inhibited by cobalt ions and p chloromercuribenzoate. The acylase also showed peptidase activity with some di- and tripeptides. A protein fraction with A933 L-amino acid acylase activity from blocked mutant 1501 lacked OA-6129A-depantothenylating activity. PMID- 4019313 TI - Enantiodivergent total syntheses of (-)-nanaomycin D and its enantiomer, (+) kalafungin. PMID- 4019312 TI - The cloned Streptomyces bikiniensis A-factor determinant. AB - By cleavage with restriction endonucleases and cloning the resultant fragments, the A-factor determinant cloned from streptomycin-producing Streptomyces bikiniensis (Horinouchi et al., J. Bacteriol. 158: 481 approximately 487, 1984) was narrowed down to a 1.1-kilobase (kb) fragment. A hybrid multicopy plasmid (pAFB15) carrying the 1.1-kb fragment conferred A-factor production in a large quantity to A-factor-deficient mutants of S. bikiniensis and Streptomyces griseus as well as afsA mutants of Streptomyces coelicolor A3(2). A transcriptional control signal in the 1.1-kb fragment was identified by using a promoter-probe vector pARC 1. Plasmid pAFB15 also caused A-factor production with a marked gene dosage effect in four different Streptomyces strains which originally had no ability to produce A-factor and no DNA sequence homologous to the S. bikiniensis A-factor determinant, suggesting that precursors of A-factor are common metabolites in streptomycetes and that acquisition of only a single key enzyme encoded by the 1.1-kb fragment is sufficient for Streptomyces strains to synthesize A-factor. PMID- 4019314 TI - Sugar-ring analogs of daunorubicin: 3'-epidaunorubicin, 3'-hydroxy-3',5' diepidaunorubicin and 3',6'-dihydroxy-3',5'-diepidaunorubicin. PMID- 4019315 TI - Studies on the biosynthesis of bialaphos (SF-1293). 6. Production of N-acetyl demethylphosphinothricin and N-acetylbialaphos by blocked mutants of Streptomyces hygroscopicus SF-1293 and their roles in the biosynthesis of bialaphos. PMID- 4019316 TI - Structural characterization of glycopeptide antibiotics related to vancomycin by fast atom bombardment mass spectrometry. AB - A series of glycopeptide antibiotics related to the vancomycin-ristocetin family have been successfully analyzed by fast atom bombardment mass spectrometry (FABMS). The FAB mass spectra of glycopeptides weighing up to 2,100 daltons exhibit intense molecular ions and fragment ions from which information concerning carbohydrate composition and sequence are readily obtained. Careful adjustment of the FABMS experimental conditions has enabled the accurate masses of the glycopeptides to be determined by high resolution FABMS with an accuracy of better than six ppm. Comparison of the observed molecular ion cluster pattern with calculated isotope distributions reveals the precise number of chlorine atoms in these molecules, which, together with the accurate mass data, can be used to restrict the number of possible elemental compositions to a meaningfully small value. These techniques have been used to characterize several glycopeptides of known structure including ristocetin, actinoidin, avoparcin, vancomycin and A35512B, as well as aridicins A, B and C which are three new, novel members of the vancomycin class. PMID- 4019317 TI - Synthesis and antimicrobial activity of pyrimidinylureidocephalosporins. AB - The synthesis of a series of 7R-[(R)-2-[3-[5-pyrimidinyl]ureido]-2 (aryl)acetamido]-3-cephem-4- carboxylates is described. Variation of the substituents at the 3-position in the cephem nucleus, at the 2-position of the pyrimidine ring, and of the phenyl residue in the acyl side chain is carried out. Qualitative structure-activity relationships in this series are discussed. VX-VD 2, the most interesting compound, exhibits broad antimicrobial activity against Gram-negative bacteria, including Pseudomonas aeruginosa. PMID- 4019318 TI - CC-1065 transformations. AB - This report defines the transformations that antitumor antibiotic CC-1065 underwent under basic and acidic conditions. The isolation, purification, characterization, and biological properties of a cyclopropapyrroloindole fragment, and an acidic fragment, PDE-I dimer, from a mild alkaline fragmentation and the phenolic product, AAP, resulting from alkylation of acetic acid by the cyclopropyl function are described. PMID- 4019319 TI - Application of a tissue culture microtiter test for the detection of cytotoxic agents from natural products. AB - A method is described by which the growth inhibitory effects of cytotoxic compounds and fermentation broth cultures on adherent tumor cell lines can be quantitated. Cells are seeded into 96-well microtiter plates and 16 hours later the test compounds or broths are added to the wells. Cell growth is measured after three days (B16 mouse melanoma cells) or six days (HT-29, human colon carcinoma cells) by first fixing adherent cells, staining with Giemsa stain, washing away excess stain, then solubilizing stained cells with HCl. Absorbance is determined using a microELISA spectrophotometer and the data are transferred to and analyzed by a computer. The assay is rapid and reproducible and can be used to identify fermentation broths with cytotoxic components. Addition of DNA into the assay mixture (cells plus compound) inhibits the cytotoxic activities of certain DNA-reactive agents. The results of this study demonstrate the application of this assay system for primary and secondary evaluation of fermentation broths for in vitro antitumor activity. PMID- 4019320 TI - Activity of safracins A and B, heterocyclic quinone antibiotics, on experimental tumors in mice. AB - Safracins A and B, new antibiotics produced by Pseudomonas fluorescens A2-2, were tested for antitumor activity against mouse tumors. Structurally, these antibiotics belong to the saframycin family of antibiotics, and safracin B is 21 hydroxysafracin A. They showed antitumor activity against L1210 and P388 leukemias and B16 melanoma. The toxic and effective doses of safracin B were much lower than those of safracin A. Safracin B also prolonged the life span of tumor bearing mice to a greater extent than safracin A. These results indicate that the alpha-carbinolamine structure plays an important role in the antitumor action of this type of antibiotic. Both safracins were, however, ineffective when their administration route differed from that used for inoculating tumor cells. PMID- 4019322 TI - Cloning of a gene from Streptomyces species complementing argG mutations. AB - A gene that complements argG mutations was cloned from Streptomyces coelicolor and Streptomyces lividans by using pIJ702 as a vector. The recombinant plasmid pMCP25 complemented argG mutations of S. lividans and S. coelicolor. The inserted DNA of pMCP25 was able to hybridize with argG+ strains of S. lividans, S. coelicolor, S. lavendulae and S. alboniger but not with argG mutants of these strains. PMID- 4019321 TI - Mitogenic potentials of bestatin, amastatin, arphamenines A and B, FK-156 and FK 565 on spleen lymphocytes. AB - The following aminopeptidase (AP) activities were found to be associated with the surface of mouse spleen cells: Leu-AP (138 pmol/10(5) cells X minute) and AP-B (16 pmol/10(5) cells X minute with Lys-beta-naphthylamide as substrate and 21 pmol/10(5) cells X minute with Arg-beta-naphthylamide substrate); AP-A activity was not detected by the assay system applied. The immunoactive peptide bestatin inhibited the Leu-AP, while AP-B activity decreased in the presence of both arphamenines A and B and bestatin. No effects on these enzymes were caused by amastatin (an AP-A inhibitor), FK-156, FK-565 and Bu-2743E; the latter peptide turned out to be not an inhibitor of cell surface associated microsomal Leu-AP but an inhibitor of cytosolic Leu-AP. The immunoactive peptides bestatin, arphamenines A and B, and amastatin increased [3H]thymidine incorporation into spleen cells containing lymphocytes and macrophages. These mitogenic actions were not observed when macrophages were removed from the cultures or the cells had been stimulated with ConA or LPS. The lactoyl- and heptanoyl peptides FK-156 and FK-565 caused a mitogenic action on lymphocytes independently of the presence of macrophages. The inhibitor of cytosolic Leu-AP did not change the incorporation into lymphocytes. PMID- 4019323 TI - Temperature dependence of lincomycin production by thermoduric Streptomyces espinosus strains. PMID- 4019324 TI - The use of fast atom bombardment mass spectrometry for the determination of structures of everninomicins. PMID- 4019325 TI - Biosynthetic origin of carbons 1 and 2 of naphthyridinomycin. PMID- 4019326 TI - Microbial conversion of epsilon-pyrromycinone to 1-hydroxy-11-deoxycarminomycin II. PMID- 4019327 TI - Coding of amplitude-modulated tones in the central auditory system of catfish. AB - In the catfish central acoustic system information is coded by two subsets of units. Type I units show little or no adaptation, type II units adapt rapidly, and some units are transitional, showing moderate adaptation. The two groups of units also respond differently when exposed to sinusoidal amplitude modulation of the signal's carrier frequency. The tonic, less readily adapting type I units code over an intensity range of about 30 dB, are fairly insensitive to intensity changes, and follow stimulus envelopes of 60 Hz and less. They apparently discharge in response to the actual intensity of the signal rather than in response to something in its temporal pattern. The onset-sensitive, fast-adapting type II units on the other hand are restricted to an intensity range of only 10 dB, show greater sensitivity to intensity changes, and are capable of following the temporal pattern of amplitude-modulated stimuli exceeding 100 Hz. These units appear to code the temporal changes in the stimulus intensity irrespective of the absolute intensity of the signal. PMID- 4019328 TI - Auditory brainstem and middle latency responses in non-human primates. AB - Auditory brainstem (ABR) and middle latency responses (MLR) were obtained from each ear in 8 crab-eating macaques, 4 white-handed gibbons, 4 siamangs and 2 orangutans. Macaques ranged in age from 5 days to 15 years with the 6 older animals in age-matched, male-female pairs. From each animal, latency-intensity functions were obtained and multiple MLR recordings were measured at 60 and 70 dB. Latency-intensity functions, interwave intervals, thresholds and percent detectability were calculated for ABR waveforms. Waves II and IV were largest in amplitude and were most consistently detected at low stimulus intensities in all species tested. Waves I and II had adult latencies in the youngest animal tested (5-day-old macaque), while waves III and IV were prolonged in comparison to the 15-month-old macaque, in whom latencies had reached adult values. There were no apparent sex differences in evoked potentials in the age-matched, male-female pairs. A broad, negative MLR at 7-13 ms was observed in all animals. Longer latency MLRs varied among animals of the same species, but were replicable in some individuals, including the youngest macaque (5 days) and orangutan (7 months). These data were compared to responses obtained in humans, other primates and other vertebrates. PMID- 4019329 TI - Permeability to chloride ions of the cochlear partition in normal guinea pigs. AB - The endocochlear potential and Cl- activities in the endolymph and perilymph of guinea pigs were simultaneously measured with a pair of double-barreled Cl- sensitive liquid-membrane electrodes. Under normal conditions the mean Cl- activity was 96.6 mEg/l in the endolymph and 93.5 mEq/l in the perilymph. The mean Cl- concentration determined by potentiometric titration was 132.3 mM in the endolymph and 121.8 mM in the perilymph. The permeability to Cl- of the cochlear partition was determined after active transport was abolished by permanent anoxia. The modified permeability coefficient and conductance for Cl- of the cochlear partition were computed from the rate of decrease in the Cl- concentration of the endolymph and its electrochemical potential difference between the endolymph and perilymph. The mean modified Cl- conductance and permeability coefficient of the cochlear partition were (10.7 +/- 4.25) X 10(-3) omega -1 . cm-3 and (22.58 +/- 8.95) X 10(-6) s-1 respectively, when averaged from 10 to 30 min after onset of anoxia. Our results indicate that the cochlear partition is relatively permeable to Cl-, when compared to its permeability to K+. Possible coupling between Cl- and water movement across the cochlear partition is discussed. PMID- 4019330 TI - Structure of the barn owl's (Tyto alba) inner ear. AB - The basilar papilla of the Barn Owl's (Tyto alba) cochlea was found to be 9.5 11.5 mm long. Histological examination revealed that the sensory hair cells had a characteristic distribution: The proximal half contained mostly typical short cells; tall hair cells were present only on the distal half along with many short cells. Lenticular short cells occupied the proximal tip of the papilla. Another unusual feature of the proximal part was a dense fibrous mass in the basilar membrane. This was absent from the distal one-fourth. PMID- 4019331 TI - A comparison of brainstem, whole-nerve AP and single-fiber tuning curves in the gerbil: normative data. AB - Tuning curves were obtained from brainstem responses (BSRs) and whole-nerve action potential (AP) responses of gerbils using a forward masking procedure. These are compared with single-fiber tuning curves of the gerbil. The broadness of the tips, tip-to-tail ratios and the slopes of the high frequency sides of the BSR tuning curves are similar to those of the AP curves for probe frequencies ranging from 1 to 8 kHz. Also, the BSR and AP curves share a number of characteristics with single-fiber tuning curves. These results suggest that, like the AP, components of the BSR can be used to measure frequency selectivity in the periphery of an intact auditory system. PMID- 4019332 TI - A monaural space map in the guinea-pig superior colliculus. AB - Under anechoic conditions, a horizontal array of loudspeakers was used to investigate the representation of auditory space in the guinea-pig superior colliculus. We have previously demonstrated that in animals with both ears intact, there is a topographical representation of the azimuthal dimension of auditory space in the deep layers of this nucleus. In the present study, we have investigated the contribution of monaural and binaural cues to the generation of the auditory space map. Occlusion of one ear or unilateral cochlear destruction resulted in omnidirectional responses in all cells to white-noise stimuli more than 20 dB suprathreshold. The sensitivity of cells to the location of sound at or near threshold was, however, unchanged and we demonstrate the presence of a threshold, monaural auditory space map. This monaural space map was destroyed by removal of the contralateral pinna and concha which resulted in all cells responding best, at threshold, to sounds opposite the external auditory meatus. Measurements of cochlear microphonic (CM) potentials, although variable, revealed that the pinna and concha may result in location-specific changes in the spectral pattern at the tympanic membrane. PMID- 4019333 TI - A comparison of psychophysical tuning curves obtained using bandpass and modulated noise. AB - No significant difference was found between psychophysical tuning curves obtained using narrowband noise maskers generated by two techniques: digital bandpass filtering and amplitude modulation. PMID- 4019334 TI - Selection for increased weaning or yearling weight in Hereford cattle. I. Measurement of selection applied. AB - Selection was applied from 1964 to 1978 for increased weaning weight (WWL) or yearling weight (YWL) in two Hereford lines with an Angus line maintained as an unselected control line (CL). Each line was maintained with 50 cows and four sires (two sires selected each year and each used for 2 yr). Traits analyzed were birth weight (BW), preweaning daily gain (WDG), weaning weight (WW), weaning conformation grade (WG), weaning condition score (WC), weaning to yearling daily gain (YDG), yearling weight (YW), yearling conformation grade (YG) and yearling condition score (YC). After 15 yr of selection, a total of 3.22 generations of selection had occurred in both WWL and YWL. Average selection differentials in standard measure per generation for WWL, YWL and CL, respectively, were: BW, .44, .51, .0; WDG, .95, .81, .09; WW, .97, .85, .09; WG, .66, .57, .09; WC, .60, .38, .02; YDG, .30, .79, .38; YW, .80, 1.05, .25; YG, .63, .62, .34 and YC, .45, .64, .24. The proportionate contribution of sire selection (delta S) to the average midparent selection differential per generation (delta M) was 70% in WWL and 76% in YWL. Selection indexes in retrospect were also calculated. PMID- 4019336 TI - Sire X environment interactions in beef cattle weaning weight field data. AB - Weaning weight field records, supplied by the American Polled Hereford Association, were used to examine sire X environment interactions. Sire X herd/region and sire X contemporary group/herd interactions were evaluated from a data set containing 19,503 records. Sire X region interaction was evaluated from a data set containing 8,659 records. The genetic correlations of sire progeny performance across contemporary groups/herd were .59 and .37 across herds and contemporary groups/region. The average genetic correlation of sire progeny performance across regions was .64. Heritability of weaning weight was .11 across regions, .17 within region and .28 within herd. Mixed-model sire analyses of Polled Hereford weaning weight field records should include sire X herd/region and sire X contemporary group/herd random effects to reduce the sire X environment effects particular to any herd or contemporary group, and to account for the distribution of sire progeny across herds and contemporary groups in the estimation of prediction error variance. It may be necessary to perform separate sire analyses for some regions to evaluate the breeding values of sires in regions where rank changes are likely to occur. PMID- 4019335 TI - Selection for increased weaning or yearling weight in Hereford cattle. II. Direct and correlated responses. AB - Selection was applied from 1964 to 1978 for increased weaning weight (WWL) or yearling weight (YWL) in two Hereford lines. An Angus line was maintained as an unselected control line (CL). Each line was maintained with 50 cows and four sires each year (two sires selected each year and used for 2 yr). Primary traits measured in the lines were birth weight (BW), preweaning daily gain (WDG), weaning weight (WW), weaning conformation grade (WG), weaning condition score (WC), weaning to yearling daily gain (YDG), yearling weight (YW), yearling conformation grade (YG) and yearling condition score (YC). Averaged over two methods, estimated genetic responses/generation (in standard deviation units) in WWL and YWL were: BW, .29, .26; WDG, .17, .15; WW, .22, .19; WG, .19, .26; WC, .12, .12; YDG, -.02, .04; YW, .08, .14; YG, .19, .16; YC, -.13, -.03. The realized heritability estimates were .23 and .15 for WW and YW, respectively. The realized genetic correlation between WW and YW was .69. Progeny from crosses of selected WWL and YWL sires to Angus cows had similar feedlot and carcass performance. At the end of the study, milk yield and composition were similar for mature cows in WWL and YWL. PMID- 4019337 TI - Effect of dietary calcium on selenium retention in postweaning swine. AB - Two experiments were conducted to evaluate the effect of dietary Se and Ca on Se utilization in postweaning swine. Two levels of dietary Se (.3 or 5.0 ppm) supplemented as sodium selenite and four levels of total dietary Ca (.50, .80, 1.10 or 1.40%) in a 20% protein, corn-soybean meal diet were evaluated. Inorganic Ca was supplied from dicalcium phosphate and limestone. In Exp. I, 135 pigs weaned at 4 wk of age were allotted by sex, litter and weight and fed a basal diet for 7 d and then their treatment diets for a 28-d period. Plasma and tissue were collected at the end of the trial for Se concentration and glutathione peroxidase (GSH-Px) activity. Dietary Ca had no effect on gain or feed measurements but 5.0 ppm Se depressed daily gain slightly. When 5.0 ppm dietary Se was fed, there resulted higher liver, kidney, heart and longissimus muscle Se concentrations than when .3 ppm was provided, but dietary Ca had no effect on tissue Se values within each dietary Se level. Plasma GSH-Px increased when higher dietary Se was provided, whereas neither heart nor liver GSH-Px activity was affected by dietary Se or Ca level. In Exp. II, a 5-d balance trial was conducted with 32 barrows after adjustment to their treatment diet for a 28-d period. Selenium retention increased quadratically as dietary Ca increased, whereas Ca retention was not affected by dietary Se. These results suggest that low dietary Ca levels may reduce total Se retention but not Se metabolism within body tissue. PMID- 4019338 TI - Effect of dietary phosphorus on selenium retention in postweaning swine. AB - Two experiments were conducted to evaluate the effect of dietary Se and P levels on Se retention in postweaning swine. A 20% protein corn-soybean meal diet at two dietary Se levels (.3 and 5.0 ppm) and four total P levels (.50, .70, .90, 1.10%) were fed. Supplemental Se was provided from sodium selenite with inorganic P from dicalcium phosphate. In Exp. I, 151 pigs weaned at 4 wk of age were allotted by sex, litter and weight and fed their treatment diets for 28 d after a 7-d adjustment to a basal diet. Dietary Se level had no effect on performance measurements. As dietary P level increased, there was an increase in daily gain, feed intake and a decrease in feed to gain ratio. Dietary P resulted in similar plasma, longissimus muscle and kidney tissue Se values within each dietary Se level, while liver Se declined as dietary P level increased. Dietary P level had no effect on plasma, heart or liver glutathione peroxidase (GSH-Px) activity. In Exp. II, 32 barrows, after being fed their diets for a 28-d period, were placed in individual metabolism crates where a balance trial was conducted. Dietary P level reduced absolute and percentage Se retention, particularly at dietary P levels of .90 and 1.10%. Phosphorus retention was not affected by dietary Se. Neither dietary P nor Se level had any effect on N retention. These results suggest an effect of dietary P level on Se retention and liver Se, particularly at dietary P levels above the pig's P requirement, while the effect is minimal at or below the pig's P requirement. PMID- 4019339 TI - Changes in plasma concentrations of thyroxine and triiodothyronine in beef steers fed different levels of propylthiouracil. AB - Three Latin-square trials were conducted to determine the effects of feeding the thyroid depressant propylthiouracil (PTU) on plasma concentrations of thyroxine (T4) and triiodothyronine (T3) in feedlot steers. In trial 1, four steers were fed 0, 1, 2 or 4 mg PTU/kg body weight daily during five 35-d experimental periods. In trial 2, eight steers were fed 0, .5, 1 or 2 mg PTU/kg body weight daily during five 28-d periods. In trial 3, three steers were fed 0, 1 or 4 mg PTU/kg body weight daily during the first 3 d in each of three 28-d periods. In general, feeding PTU caused increases in plasma T4 concentrations that peaked 5 to 7 d after feeding started. Concurrently, T3 concentrations tended to decrease when PTU was fed. The effects of PTU on hormone concentrations were apparent within approximately 1 to 4 h after PTU feeding started. Furthermore, when PTU was not fed, T4 and T3 concentrations appeared to have rhythmic cycles of 90 and 111 min, respectively, and PTU treatment appeared to interrupt this cyclical pattern. After the initial PTU response, the dose response relationship between PTU level and plasma hormone concentration was not linear. Both 4 and 2 mg PTU appeared to depress both T4 and T3 concentrations, suggesting direct inhibition of the thyroid gland and, for the 1-mg PTU treatment, T4 tended to stabilize at concentrations significantly greater than for 0 mg PTU, while T3 concentrations for 1 mg PTU were slightly lower than for 0 mg PTU.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4019340 TI - Rumen fermentation characteristics, nitrogen balance and growth in lambs fed methane digester effluent. AB - A laboratory silo trial, two lamb metabolism trials and a lamb growth trial were conducted to compare the nitrogen (N) value of swine methane digester effluent (MDE) to that of urea. Using laboratory silos (four/treatment), fermentation characteristics were measured for silages containing cracked corn, ground wheat straw and MDE added at levels of 0, 4, 8 or 12% of silage dry matter (DM). Lactic acid concentration increased linearly with up to 8% MDE addition, but then decreased (P less than .05; quadratic) with 12% MDE. Butyric acid was highest (P less than .05; linear) with 12% MDE, indicating an undesirable fermentation. In a metabolism study, DM, organic matter and N digestibilities and N balance were similar (P greater than .10) between urea and MDE, but DM digestibility was lower (P less than .05) for ensiled diets (52%) than diets fed fresh daily (59.4%). Mean ruminal volatile fatty acid, ruminal ammonia-N and plasma urea-N concentrations were similar (P greater than .10) between urea- and MDE-fed lambs. Plasma urea-N was higher (P less than .05) and ruminal isovaleric acid lower (P less than .05) in animals fed ensiled than fresh diets. In the second metabolism trial, digestibility of N was lowest (P less than .05) for MDE (51.2%) and highest for soybean meal (SBM; 71.8%), but N balance was similar among all diets.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4019341 TI - Effects of monensin on monovalent ion metabolism and tissue concentrations in lambs. AB - A study consisting of two trials was conducted to determine the effects of monensin on the apparent absorption and retention of sodium (Na) and potassium (K) and to examine changes in tissue and ruminal fluid concentrations of these minerals in lambs. Eight lambs (39 kg) were used in trial 1 and 10 lambs (37 kg) were used in trial 2. Animals were used in randomized block designs, blocked by weight, and fed a high concentrate diet with or without 20 mg/kg monensin. Trials began with a dietary adjustment period lasting 18 d in trial 1 and 21 d in trial 2. Animals were then placed in metabolism stalls for a 10-d stall adjustment period followed by a 12-d collection period. Collections for mineral balance were made during the first 10 d of the collection period. Blood and ruminal fluid samples were obtained on d 11 of the collection period. Lambs were slaughtered on d 12 of the collection period and tissue samples were collected. Sodium retention decreased (P less than .05) 86.2% when monensin was fed. Apparent K absorption increased (P less than .05) 16.7%, while K retention increased (P less than .10) 52.6% when monensin was fed. In lambs fed monensin, ileal Na decreased (P less than .10) 13.8%. These results indicate that dietary monensin alters the metabolism of Na and K in lambs. PMID- 4019342 TI - Effects of monensin on Mg, Ca, P and Zn metabolism and tissue concentrations in lambs. AB - A study consisting of two trials was conducted to determine the effects of monensin on the apparent absorption and retention of magnesium (Mg), phosphorus (P), calcium (Ca) and zinc (Zn) and to determine mineral changes in tissue and ruminal fluid. Eight lambs (39 kg) were used in trial 1, and 10 lambs (37 kg) were used in trial 2. Animals were blocked by weight and fed a high concentrate diet with or without 20 mg/kg monensin. Trials began with a dietary adjustment period lasting 18 d in trial 1 and 21 d in trial 2. Animals were then placed in metabolism stalls for a 10-d stall adjustment period followed by a 12-d collection period. Collections to determine mineral balance were made during the first 10 d of the collection period. Blood and ruminal fluid samples were taken on d 11 of the collection period. Lambs were slaughtered on d 12 of the collection period and tissue samples were collected. Monensin supplementation increased (P less than .05) Mg retention 42.0%. Urinary Ca excretion decreased (P less than .05) 60.0% when monensin was fed. Monensin supplementation decreased (P less than .05) liver Ca and bone Ca, 45.5 and 2.9%, respectively. Apparent P digestibility increased (P less than .05) 40.0% and P retention increased (P less than .10) 26.8% due to monensin supplementation. Both apparent absorption and retention of Zn increased (P less than .01) 50.0 and 45.0%, respectively, with monensin supplementation. Ruminal fluid Zn concentrations decreased (P less than .05) 33.0% with the addition of monensin.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4019343 TI - Effect on the ewe and lamb of low zinc intake throughout pregnancy. AB - Throughout pregnancy, 30 primiparous Finn cross ewes were given a low Zn (less than or equal to 1 ppm) semi-purified diet. A 100-g hay supplement was fed three to seven times/week. Supplemental Zn (20 ppm) was provided in the drinking water of 14 ewes. At parturition, lambs were removed from ewes before suckling. Viable lambs not taken for tissue analysis were given 200 ml cow colostrum and raised on an artificial feeder. Throughout gestation, unsupplemented (-Zn) ewes gained less weight and had lower plasma Zn levels than Zn-supplemented (+Zn) ewes. One -Zn ewe was not pregnant, three aborted, one resorbed, one delivered mummified twins at term and two delivered malformed lambs. Average weight of lambs born to -Zn ewes d 136 or later (excluding mummified twins and one weighing less than 20% as much as its twin) was 1.8 +/- .6 (SE) kg. Only three lambs born to -Zn ewes were vigorous enough to put on the artificial feeder; none survived. One +Zn ewe was not pregnant. Of 23 lambs born to the remaining +Zn ewes, five were used for tissue analysis, two lambs of triplets were born dead, twins born d 138 died at birth. One twin died 6 d after birth. The 14 remaining lambs were weaned in good health. Average birth weight of +Zn lambs was 3.3 +/- 1.0 kg. Increased salivation was seen in -Zn ewes after 6 wk of low Zn intake.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4019344 TI - Cellular and enzyme-histochemical aspects of adipose tissue development in obese (Ossabaw) and lean (crossbred) pig fetuses: an ontogeny study. AB - The cellular and enzyme-histochemical differentiation of subcutaneous adipose tissue was studied in lean and obese pig fetuses at several ages. Positive reactions for a variety of cytosolic and organellar enzyme markers indicate metabolic competence of fetal adipocytes despite their small size (12 to 15 microns). Reactions for several enzymes decreased with fetal age and may be associated with a qualitative change in activity of adipocyte organelles. Age associated increases in two lipogenic enzymes were observed in obese adipocytes. Observations on developing cells around hair follicles in the younger fetuses indicated significant temporal lags between the appearance of detectable enzyme activities in adipocytes. Enzyme activities in order of appearance were: dehydrogenases (cytosolic and mitochondrial), lipoprotein lipase and esterase. Esterase activity and several other enzymes were never observed in lipid positive cells that were not spherical. A proportion of hair follicle associated adipocytes in 110-d-old lean fetuses were histochemically and morphologically similar to brown adipocytes in the young rat. There was no evidence for brown adipocyte like cells in obese fetuses. Finally, comparison of the enzyme histochemical differentiation of lean and obese fetal adipocytes indicates that fetal adipocytes become sensitive to external stimuli between 70 and 90 d of gestation. PMID- 4019346 TI - Enzyme histochemical studies in an ontogeny study of muscle development in Ossabaw and decapitated fetuses: cellular reactions. AB - Fetuses were decapitated in one uterine horn in each of 14 sows at 45 d of gestation. Control (C) and decapitated (D) fetuses were removed by Caesarean section from three sows at 65 d of gestation (total of 10 D and 10 C fetuses), two sows at 85 d (six D and six C fetuses) and nine sows at 110 d (nine C and nine D fetuses) of gestation (Exp. 1). In Exp. 2, four to six fetuses were removed from each of two Ossabaw (O) gilts and three crossbred (C, Landrace X Yorkshire) gilts at 70 d of gestation, from three C and O gilts at 90 d of gestation and from three C and two O gilts at 110 d of gestation. In Exp. 1, one semitendinosis muscle was removed for histochemistry, whereas the contralateral muscle was removed and weighed. A medial portion of biceps femoris muscle was removed and used for histochemistry in Exp. 2. In both experiments, transverse sections (cryostat) of muscle were stained for lipid, glycogen (PAS) and the following enzymes: acid ATPase, NADH-TR, NADPH-TR, malate dehydrogenase (NAD- and NADP-dependent reactions; MDH), succinate dehydrogenase (SDH), alpha-glycerol phosphate dehydrogenase (with and without NAD; alpha-GPDH), isocitrate dehydrogenase (NAD dependent; ICDH), esterase, lipoprotein lipase and lipase. In Exp. 1, body and muscle weights of the two groups were not significantly different (P greater than .05) at 65 d of gestation, whereas D fetuses were smaller and had lighter weight muscles (P less than .05) at 85 d of gestation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4019345 TI - Adipocyte development in primary rat cell cultures, effect of cell density and serum source. AB - The development of adipocytes was studied in primary cultures of rat adipose tissue stromal-vascular cells on collagen-coated glass coverslips. The effects of cell density and serum source on lipoprotein lipase (LPL), esterase and lipid histochemistry were evaluated. With a mixture of fetal calf serum (FCS; 2%), horse serum (2%) and pig serum (PS; 10%), large and loosely arranged clusters of adipocytes developed with time through an increase in cell number and size. An inverse relationship was observed between cell size and the number of adipocytes in a cluster. Lower cell densities were associated with large cells and the densest areas contained smaller cells. Unilocular adipocytes were observed by d 13 after plating and were generally absent from the densest area of the coverslips. Histochemically detectable LPL activity was demonstrable before lipid deposition in adipocyte clusters. A comparison of FCS (10%) and PS (10%) as the only serum sources indicated higher level of adipocyte esterase activity and lipid deposition in PS cultures. Cultures of cells from weanling (21 to 28 d old) and old (18 mo) rats were similar, whereas cells from younger rats (2 to 4 d old) formed denser cultures that contained fewer adipocytes. These adipocytes were small (less than 30 micron) and morphologically homogeneous (all multilocular). When cells from the very young rats (2 to 4 d old) were plated at low densities, an inverse relationship between cell size and number of cells in a cluster was also observed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4019347 TI - A technique for isolation of bovine hepatocytes. AB - A technique for preparing viable and functional isolated hepatocytes from cattle liver is described. The basic procedure, which was adapted from published methods established for laboratory species, employed a two-step in vitro vascular perfusion of the caudate lobe: (1) perfusion with a calcium-free buffer containing ethylene bis(oxyethylenenitrilo)tetraacetic acid (EGTA) for removal of blood cells and extracellular calcium and (2) perfusion with calcium-fortified buffer containing collagenase for cell dissociation. Hepatocyte suspensions prepared from the caudate lobes of 20 cattle possessed a mean viability of 81.3% as determined by trypan blue exclusion. Mean yield was 2.2 X 10(7) viable hepatocytes/g of liver (wet wt). Viable hepatocytes utilized O2 at a rate 2.82 times greater than nonviable hepatocytes. Biochemical function of the hepatocyte suspensions was assessed by rates of gluconeogenesis and fatty acid oxidation. Glucose production from added lactate ranged from .88 to 1.47 mumol X min-1 X g-1 of liver tissue (dry wt). Both gluconeogenic and fatty acid oxidation rates were substantially greater in isolated hepatocytes when compared with liver slices. Isolated hepatocyte contained .398 +/- .033 (SE) nmol cytochromes P-450/mg microsomal protein and .285 +/- .025 nmol cytochrome bs/mg microsomal protein, which was comparable with amounts in liver tissue from the same animals (.568 +/- .056 and .298 +/- .033 nmol/mg protein, respectively). No significant decline of either cytochrome was detectable for isolated hepatocytes for up to 5.5 h after euthanasia. The potential usefulness of isolated bovine hepatocytes in xenobiotic metabolism studies is illustrated by the epoxidation of aldrin. PMID- 4019348 TI - Toxicity potential of absorbed-retained ethylene oxide residues in culture dishes on embryo development in vitro. AB - Four hundred eight-cell mouse embryos were cultured in vitro in either polystyrene (plastic) dishes (Exp. 1) or watch glasses (Exp. 2) to analyze the toxicity potential of absorbed-retained ethylene oxide (EtO). Culture dishes were gas-sterilized with Anprolene equipment and allowed to aerate (21 C) for varying durations. Post-sterilization EtO residues, as determined by weight measurement, were eluted from polystyrene dishes at an exponential rate. After 1 wk of aeration, .625 mg EtO was retained/g of polystyrene product. To determine the effect of EtO residue on in vitro culture, embryos were collected from superovulated donor mice (C57BL/6N), pooled in a modified Dulbecco's phosphate buffered saline (PBI) medium and then randomly allotted to dishes subjected to various aeration durations. Embryos were cultured in Whitten's medium +3 mg/ml bovine serum albumin (BSA) under a humidified 5% CO2 in air atmosphere at 37 C. Gross assessments of embryo development were made using standard morphology and quality grading systems and a fluorescein diacetate staining assay. In Exp. 1, embryo development was retarded at the 8- to 16-cell stage when less than or equal to 12 h aeration of polystyrene dishes was permitted. Aeration for 24 and 36 h resulted in suboptimal embryo development with fewer (P less than .01) blastocysts and greater degeneration rates at 48 h of in vitro culture compared with the control (manufacturer-packaged dishes, no EtO) and 1-wk aeration treatment groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4019349 TI - Teaching between-class generalization of toy play behavior to handicapped children. AB - In this study, young children with severe and moderate handicaps were taught to generalize play responses. A multiple baseline across responses design, replicated with four children, was used to assess the effects of generalization training within four sets of toys on generalization to untrained toys from four other sets. The responses taught were unique for each set of toys. Across the four participants, training to generalize within-toy sets resulted in complete between-class generalization in 11 sets, partial generalization in 3 sets, and no generalization in 2 sets. No generalization occurred to another class of toys that differed from the previous sets in that they produced a reaction to the play movement (e.g., pianos). Implications for conducting research using strategies based on class interrelationships in training contexts are discussed. PMID- 4019350 TI - The use of peer monitors to reduce negative interaction during recess. AB - The negative interactions of a midly retarded child, Dennis, were reduced in three daily recess periods, with the use of a point system. Adult monitors initiated the intervention in the morning recess; reductions achieved during adult monitoring were maintained in that recess during two subsequent conditions: peer monitoring and self-monitoring. Dennis' negative interactions were reduced next in the afternoon recess by peer monitors. Again, reductions were maintained during a subsequent self-monitoring condition. Finally, during the noon recess, Dennis was trained to serve as a peer monitor for Ed, a moderately retarded classmate. Dennis' rate of negative interactions quickly decreased following his appointment as a peer monitor. The results show that a point system, originally designed for adult monitoring, can be adapted without loss of program effectiveness for peer monitoring or self-monitoring. The results also suggest that classmates who serve as peer monitors may benefit significantly from their role. The conditions under which these therapeutic effects occur and the role that treatment order effects may play in this process require further investigation. PMID- 4019352 TI - Evaluation of reinforcer preferences for profoundly handicapped students. AB - Five students classified as profoundly/multiply handicapped were trained to use microswitches to indicate reinforcer preferences. The students were trained to emit a designated motoric response (raise arm or raise head) which in turn activated a microswitch. The microswitches were connected to battery-operated toys and devices, and served to provide immediate, contingent consequences to the students for their motoric responding. The results of the investigation were evaluated within a multiple baseline (across students) with alternating treatments (potential reinforcers) design. During baseline, the students were provided with the switches and devices, but the switches were not connected to the devices. During the training conditions, the switches activated the devices. Evaluation of the devices was conducted by recording the cumulative frequency and duration of the students' responses. When the microswitches activated the devices during training, a substantial increase in the duration of motoric responding occurred for all students. In addition, some students performed differentially across devices, suggesting that they had reinforcer preferences. PMID- 4019351 TI - Increasing spontaneous verbal responding in autistic children using a time delay procedure. AB - One oft-cited problem with teaching speech skills to autistic children is the failure of the speech to be spontaneous. That is, the children's speech often remains under the control of the verbal behavior of others rather than under the control of other nonverbal referents in the environment. We investigated the effectiveness of a time delay procedure to increase the spontaneous speech of seven autistic children. Initially, the experiment presented a desired object (e.g., cookie) and immediately modeled the appropriate response "I want (cookie)." Gradually, as the child imitated the vocalization, the experimenter increased the time between presentation of the object and the modeled vocalization in an attempt to transfer stimulus control of the child's vocalization from the experimenter's model to the object. Results indicated that all the children learned to request items spontaneously and generalized this behavior across settings, people, situations, and to objects which had not been taught. These results are discussed in relation to the literature on spontaneous speech, prompting, and generalization. PMID- 4019353 TI - Teaching selected microcomputer skills to retarded students via picture prompts. AB - Five retarded students were taught to use picture prompts to help them access and terminate a microcomputer program. Training was provided within a multiple baseline format. Posttesting (picture prompts without feedback), and a return to baseline were later conducted for both the training program and an untrained (generalization) program. The results indicate that the program was successful in teaching the microcomputer skills to the students. In addition, all students were able to maintain their skills over a 7-day interval in which they did not have access to the microcomputer. PMID- 4019354 TI - Conditions affecting clonal growth of lymphoma cells in a semisolid matrix. AB - This study demonstrated the importance of the methods used in determining the lymphoma cell colony stimulating activity of factors derived from lymphoma cells. The in vitro colony formation in a semisolid matrix of the AKR mouse lymphoma cell line, SL 12, and three cloned derivatives, SL 12.1, SL 12.3, and SL 12.4, was studied. We show that the use of soft agar or methylcellulose as a semisolid matrix results in colony formation by the lymphoma cells only in the presence of serum. The addition of conditioned medium (CM) from lymphoma cells growing in serum-free medium does not stimulate colony growth. However, when purified agarose is used, colonies grow in a dose-dependent manner in the absence of serum and in the presence of CM. These results indicate that the type of semisolid matrix used can influence results in studies of this nature. Purified agarose provides the best environment when colony formation by lymphoma cells is used to measure the presence of growth factors in test-conditioned media. PMID- 4019355 TI - Age-dependent metabolic changes in cultured human fibroblasts. AB - The effects of metabolic poisons on the ATP content of cultured human skin fibroblasts at selected in vitro and in vivo ages were studied. Potassium cyanide, iodacetamide, and Arsenate were used to inhibit ATP restoration by glycolysis and oxidative phosphorylation. Cells treated with these metabolic poisons showed an age-dependent change in their ATP content. The decrease in cellular ATP content after exposure to these drugs was taken as an estimate of ATP turnover. It was found that there was a decrease in the ATP turnover with increasing population doubling level (i.e. in vitro age), and cells cultured from a 68-yr-old donor had a lower ATP turnover than those cultured from a neonatal donor. This decreased ATP turnover correlates with a previous finding of a decreased ability of "older" cells to be stimulated to migrate in culture and suggests that there is a metabolic component to this age-related functional deficiency. PMID- 4019356 TI - Analysis of the cytotoxic effects of light-exposed HEPES-containing culture medium. AB - The addition of N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid (HEPES) to RPMI 1640 medium markedly increases the production of cytotoxic products during exposure of the medium to visible light. The cytotoxicity has been analyzed by measuring uptake of [3H]thymidine by murine thymocytes cultured in preirradiated medium containing 25 mM HEPES. Complete inhibition of thymidine uptake was produced by exposing 50% of the culture medium to light for 3 h before addition of cells. The HEPES-mediated effect requires only that HEPES and riboflavin be exposed to light; other medium constituents are not necessary. Hydrogen peroxide is a principal cytotoxic agent produced in this system. It is demonstrated that most, but not all, of the inhibition of thymidine uptake can be attributed to hydrogen peroxide. PMID- 4019357 TI - A rapid naphthol yellow S method for measuring the cellular protein content of anchorage cultures. AB - A rapid method has been developed for measuring the cellular protein content of mono- and multilayered anchorage cultures. Fixed or air dried cultures are stained for 30 min with 0.2% Naphthol Yellow S (NYS) dissolved in 1% acetic acid. Unbound dye is removed by a series of four 2.5 min washes in 1% acetic acid, and protein-bound dye extracted with 10 mM unbuffered Tris base for spectrophotometric optical density determination at 433 nm. The NYS method exhibited a least-squares correlation coefficient of 0.99997 with the Oyama-Eagle Lowry method. PMID- 4019358 TI - Effects of fructose on human fibroblast metabolism: the application of DNA measurements as a basis for interpretation. AB - A fluorometric procedure for measuring DNA was used to study growth and metabolic responses of eight cell strains of human foreskin fibroblasts. In preliminary studies this procedure gave more precise specific activity changes in N-acetyl beta-D-glucosaminidase (NAG) than did a protein activity basis, when changes in this enzyme's specific activity were investigated as a function of experimental cell manipulation. When fibroblast growth in eight cell strains was compared in 134 mM D-fructose vs. 13.4 mM glucose-supplemented minimum essential media, a significant increase in cellular DNA (50%) and protein (45%) occurred over an 11 d period. No significant differences in media pH change, lactate production, or carbohydrate uptake occurred on a DNA basis when cell metabolism was compared over the last 24 h of culture in the two media. Cells grown in fructose containing media tended to show a reduction in NAG specific activity when compared with those grown in glucose-containing media. PMID- 4019359 TI - Syrian hamster lymphocyte cytogenetic technique and effects of blood storage on mitotic index. AB - The Syrian hamster has a diploid chromosome complement similar to humans in both number (2N = 44) and morphology. For comparative mutagenic studies with humans, a repeatable lymphocyte chromosome technique involving laboratory mammals is desirable. The reported hamster lymphocyte cytogenetic technique appears technically uncomplicated and repeatable while providing a sufficient number of metaphase cells for quantitative analysis. In order to determine the effects of storing whole-blood (in culture media) for varying time periods at 8 degrees C prior to adding a mitogen, the mitotic index was calculated following a 48-h culture period. Results indicated that storage up to six days can still result in a mitotic index adequate for cytogenetic analyses. PMID- 4019360 TI - Comparison of liquid chromatographic and bioassay procedures for determining depletion of intramuscularly injected tylosin. AB - Crossbred pigs weighing 80-110 kg were injected intramuscularly in the ham with 8.8 mg/kg tylosin. Animals were slaughtered in groups of 3 at intervals of 4 h, and 1, 2, 4, and 8 days after injection, and samples of blood, injected muscle, uninjected muscle, liver, and kidney were analyzed by liquid chromatography (LC) and by bioassay using Sarcina lutea as the test organism. The LC method was far more sensitive with a detection limit of less than 0.1 ppm, while the detection limit by bioassay was about 0.5 ppm in tissue. Results by bioassay and LC sometimes differed considerably for tissue samples. Residues in all tissues were below the tolerance limit of 0.2 ppm at 24 h, except in the injected muscle in one animal. Residues were not detected in any tissue of any animal at 48 h after treatment. PMID- 4019361 TI - Liquid chromatographic determination of narasin in feed premixes. AB - A liquid chromatographic (LC) method has been developed to determine narasin in feed premixes. Narasin is extracted from the premix with a methanol-water solvent, and the extracted solution is assayed by using LC. Recovery of narasin from a 12.5 g/lb premix is quantitative (100%), with a relative standard deviation of 1.44%. The results correlated well (coefficient 0.92) with a turbimetric bioassay method. PMID- 4019362 TI - Gas chromatographic determination of pentachlorophenol in gelatin: collaborative study. AB - Eleven collaborators participated in this study of a gas chromatographic method for the determination of pentachlorophenol (PCP) in gelatin. Following acid hydrolysis of a 2 g sample, PCP is extracted with hexane and partitioned into KOH solution. After reacidification, PCP is again extracted with hexane for determination by electron capture gas chromatography on a 1% SP-1240DA column. Three duplicate practice samples (0.0, 0.5, and 1.5 ppm) and 5 blind duplicate collaborative samples (0.0, 0.02, 0.1, 0.5, and 2.0 ppm) were analyzed by each collaborator. Mean recoveries of PCP in the collaborative samples ranged from 88% at the 0.02 ppm fortification level to 102% at the 0.1 ppm level; the overall mean recovery was 96%. Interlaboratory coefficients of variation ranged from 16.4% for the 0.1 ppm fortification level to 22.9% for the 0.5 ppm level; the overall interlaboratory coefficient of variation was 19.5%. The method has been adopted official first action. PMID- 4019363 TI - Trace level detection of chlorinated paraffins in biological and environmental samples, using gas chromatography/mass spectrometry with negative-ion chemical ionization. AB - A method is described for detection of chlorinated paraffins (CPs) in biological and environmental samples. Sample preparation includes sulfuric acid treatment followed by adsorption chromatography on alumina, which yields the CPs in one fraction that is almost free of interfering material. Using gas chromatography/mass spectrometry with negative-ion chemical ionization, the limit of detection is 5 ng (corresponding to the lower ppb range). CP levels of 30 ppm, 200 ppb, and 5 ppb were found in sewage sludge, human fat, and sediment, respectively. PMID- 4019364 TI - Formulas for calculation of extraction volumes for commonly used pesticide residue extraction procedures. AB - Formulas are presented for the calculation of extraction volume for pesticide residue procedures that use a single extraction with acetone, acetonitrile, or methanol, with or without prior dilution of these solvents with water. These formulas account for the volume change on mixing and for the volume contribution from the soluble sugars sucrose, glucose, and fructose. Results using these formulas are in agreement with the observed volumes of such mixtures within 0.3% throughout the following ranges, expressed as percent water in the mixtures: 15 38% for acetone, 4.8-59% for acetonitrile, and 9.3-33% for methanol. PMID- 4019365 TI - Radiocarbon 14C differentiation of sparkling and carbonated wines. AB - Specific 14C-activities, percent of modern 14C-activity, and calculated percent of fermentation CO2 are presented for CO2 contained in commercial sparkling wines, labeled as champagne or produced by the bulk (charmat) process. These data are given for the production years 1976-1982. The survey encompassed effervescent wines produced in Spain, Italy, West Germany, California, and New York. Addition of synthetic CO2 to approximately 40 samples represented as sparkling wines was indicated by low 14C-activities of CO2 in these wines. Data for 14C-activity were also presented for the ethanol distilled from sparkling wines for the years 1977 1980. In all cases, the 14C-activity of ethanol was appropriate to the year of vintage. PMID- 4019366 TI - Liquid chromatographic determination of hypoxanthine content in fish tissue. AB - A liquid chromatography (LC) method for determining the hypoxanthine content in fish tissues has been developed. Hypoxanthine is extracted with 0.6M perchloric acid, and determined by LC on a reverse phase microparticulate column with UV absorbance detection. The mobile phase is 0.01M potassium phosphate buffer (pH 4.5). The percent relative standard deviation for measurements by the recommended method was less than 7% with a detection limit of 10 ng. Recoveries of hypoxanthine added to various fish tissues were better than 90%. The operational errors, interferences, and recoveries for spiked samples have been investigated and compare favorably with an established xanthine oxidase enzyme method. The described LC method is simple, rapid, and specific for measuring hypoxanthine content in various fish tissues. Some post-mortem studies have indicated the method may also be used for the determination of adenosine monophosphate, inosine monophosphate, and inosine. PMID- 4019367 TI - Isotopic composition of carbon in vinegars. AB - Measurements of delta 13C and 14C-activity were performed on vinegars from various known sources. Natural vinegar can be distinguished from petrochemical acetic acid by 14C-analysis: Natural vinegar currently gives values of greater than 112% of modern activity; petrochemical acetic acid yields values of 0% of modern activity. Apple cider vinegar can be distinguished from corn-derived vinegar by delta 13C-analysis: Cider vinegar gives delta 13C-values near -26%; corn-derived vinegars yield delta 13C-values near -10%. delta 13C-Analysis also can be applied, with some restrictions, to wine vinegars. These techniques are applied to a series of retail vinegars. PMID- 4019368 TI - Simple, rapid cleanup method for analysis of aflatoxins and comparison with various methods. AB - A method is described for simple and rapid determination of aflatoxins in corn, buckwheat, peanuts, and cheese. Aflatoxins were extracted with chloroform-water and were purified by a Florisil column chromatographic procedure. Column eluates were concentrated and spotted on a high performance thin layer chromatographic (HPTLC) plate, which was then developed in chloroform-acetone (9 + 1) and/or ether-methanol-water (94 + 4.5 + 1.5) or chloroform-isopropanol-acetone (85 + 5 + 10). Each aflatoxin was quantitated by densitometry. The minimum detectable aflatoxin concentrations (micrograms/kg) in various test materials were 0.2, B1; 0.1, B2; 0.2, G1; 0.1, G2; and 0.1, M1. Recoveries of the aflatoxins added to corn, peanut, and cheese samples at 10-30 micrograms/kg were greater than 69% (aflatoxin G2) and averaged 91%, B1; 89%, B2; 91%, G1; 78%, G2; and 92%, M1. The simple method described was compared with the AOAC CB method, AOAC BF method, and AOAC milk and cheese method. These methods were applied to corn, peanut, and cheese composites spiked with known amounts of aflatoxins, and to naturally contaminated buckwheat and cheese. Recoveries were much lower for the BF method compared with our simple method and the CB method. PMID- 4019369 TI - Liquid chromatographic determination of intermediates in D&C Yellow No. 7 and D&C Yellow No. 8. AB - A sensitive, reproducible method that uses liquid chromatography in the reverse phase mode has been developed for the determination of phthalic acid, resorcinol, and 2-(2',4'-dihydroxybenzoyl)benzoic acid in D&C Yellow No. 7 and D&C Yellow No. 8. The method uses a 10 micron, C-8 column, a 1% acetic acid-methanol gradient, and UV absorption detection at 280 nm. Average recoveries of phthalic acid, resorcinol, and 2-(2',4'-dihydroxybenzoyl)benzoic acid were 100, 98, and 102%, respectively, from fluorescein standard (certifiable as D&C Yellow No. 7) spike with each compound at levels ranging from 0.13 to 1.3%. PMID- 4019370 TI - Liquid chromatographic determination of 2,4-dinitroaniline and 2-naphthol in D&C Orange No. 17. AB - A method is described for the determination of the intermediates in D&C Orange No. 17 by reverse phase liquid chromatography. The pigment is dissolved in boiling dioxane and then precipitated. The filtrate is chromatographed by isocratic elution, which is followed by a wash and equilibration. Peak area calibrations were linear. At the provisional specification levels, 99% prediction limits were 0.200 +/- 0.0012% 2,4-dinitroaniline (2,4-DNA) and 0.200 +/- 0.006% 2 naphthol. The limits of determination were 0.0023% for 2,4-DNA and 0.013% for 2 naphthol at the 99.5% confidence level. Recoveries were 98-100% for 2,4-DNA added at the 0.005-2% level, and 93-103% for 2-naphthol added at the 0.025-2% level. A survey of certified D&C Orange No. 17 samples showed that the lots contained higher levels of the intermediates than were determined previously by a cellulose column method, in which the pigment is not dissolved. PMID- 4019371 TI - Comparison of the Volhard and potentiometric methods for the determination of chloride in meat products: collaborative study. AB - A collaborative study of the determination of chloride in meat products was conducted by the International Organization for Standardization (ISO) to compare the ISO 1841 method (Volhard titration) with the FAO/WHO Codex Alimentarius Committee method (potentiometric titration). Five canned luncheon meat products containing 0.25-2.0% sodium chloride at 4 different spiking levels were analyzed by 11 laboratories. The data were analyzed by ISO statistics (ISO 5725) and by AOAC statistics (Youden-Steiner), the major differences being in the rejection of outliers and in the statement of precision parameters. Good agreement was found between the mean chloride contents of the products as determined by both methods and with the added amounts, although statistically significantly higher sodium chloride recoveries were obtained with the potentiometric method. The within laboratory variability (repeatability) is greater for the Volhard method, especially for chloride levels below 1.0%. Therefore it is proposed to set the lowest level of determination for the Volhard method at about 1.0% sodium chloride. The among-laboratories variability (reproducibility) of the potentiometric method was comparable with the results from the collaborative studies for chloride in cheese, giving acceptable values for relative standard deviations of 1.5-3.0% for meat products with 0.3-2.0% added sodium chloride. It is recommended that further work be conducted to reduce or eliminate the systematic error present with the potentiometric method as applied to meat and meat products. PMID- 4019372 TI - Effect of pH on absorbance of azo dye formed by reaction between nitrite and sulfanilamide/N-(1-naphthyl)ethylenediamine in residual nitrite methods for foods. AB - Current methods used for determining residual nitrite concentration in foods involve forming an azo dye that is measured spectrophotometrically. Conventional procedures do not specify control of pH for the final colored solution. Because many indicator dyes are pH-dependent, absorbance of the azo dye may vary not only because of nitrite concentration differences, but also because of pH variation. Thus, erroneous results could arise from a standard curve developed at one pH and used for a test sample at a different pH. This would cause an inaccurate concentration conversion from the standard curve. In this study, absorbances at lambda max wavelengths were recorded at 28 pH values (range 1.0-4.5) for each of 5 nitrite concentrations. A mathematical equation was fitted to these data and its plot gives a 3-dimensional response surface showing the relationships between pH, nitrite concentration, and absorbance. A modification for the spectrophotometric measurement of nitrite is proposed. PMID- 4019373 TI - Rapid quantitative method for simultaneous determination of benzoic acid, sorbic acid, and four parabens in meat and nonmeat products by liquid chromatography. AB - A liquid chromatographic (LC) method for the simultaneous determinations of benzoic acid, sorbic acid, and methyl, ethyl, propyl, and butyl parabens (methyl, ethyl, propyl, and butyl-p-hydroxybenzoates) in meat and nonmeat products was developed. Benzoic acid, sorbic acid, and parabens were extracted from meat and nonmeat products with 70% ethanol. After filtration, extracts were analyzed by reverse phase liquid chromatography. Homogeneously ground samples of fresh sausage and hamburger were fortified with benzoic acid, sorbic acid, and each paraben at 5 different concentrations. Average recovery (after discarding outliers) for each preservative at all 5 levels was greater than 95% with a coefficient of variation less than 5%. PMID- 4019374 TI - Liquid chromatographic determination of barbaloin (aloin) in foods. AB - A simple and rapid liquid chromatographic method is described for the determination of barbaloin (aloin, 10-D-glucopyranosyl-1,8-dihydroxy-3 (hydroxymethyl)-9(10H)-anthraceno ne) in foods. Barbaloin is extracted with water from foods containing aloe and the extract is cleaned up on a disposable cartridge by using methanol-water (55 + 45) as eluant. The eluted barbaloin is separated by liquid chromatography on a YMC A-302 column with methanol-water (50 + 50) mobile phase, and detected at 293 nm. Recoveries of barbaloin added to foods at the levels of 0.05 and 0.50 mg/g were 94.4-100%. Assay results for commercial food samples indicated that the present method is applicable to a variety of foods supplemented with aloe. PMID- 4019375 TI - Rapid gas chromatographic determination of ethylene oxide, ethylene chlorohydrin, and ethylene glycol residues in rubber catheters. AB - Isothermal gas chromatography with flame ionization detection was used to determine residual ethylene oxide (EtO), ethylene chlorohydrin, and ethylene glycol in soft rubber catheters that had been sterilized with EtO. Catheter samples were extracted by shaking with carbon disulfide, and the extract was analyzed on a 3% Carbowax 20M on 80-100 mesh Chromosorb 101 column, using nitrogen as the carrier gas. Ten replicate injections of a mixed standards solution gave coefficients of variation of 1.91, 1.23, and 4.74% for EtO, ethylene chlorohydrin, and ethylene glycol, respectively. A linear response was obtained with concentrations ranging from 1.0 to 7.9 micrograms EtO, 14.0 to 88.0 micrograms ethylene chlorohydrin, and 31.0 to 98.5 micrograms ethylene glycol. The proposed method detected as little as 0.5, 5.0, and 16.5 ng EtO, ethylene chlorohydrin, and ethylene glycol, respectively. PMID- 4019376 TI - Vitamin A and vitamin E content of infant formulas produced in the United States. AB - Vitamin A (vitamin A palmitate) and vitamin E (alpha-tocopheryl acetate) levels were determined in 77 samples of fortified infant formulas manufactured by 4 firms in the United States from 1981 to 1983 and were compared by formulation base (soy, milk) and manufacturing firm. For vitamin A and vitamin E, the mean values (IU/100 kcal) were 454 +/- 95 (range 248-614) and 2.0 +/- 0.7 (range 1.1 5.0), respectively. No significant differences (alpha = 0.05) were found in levels (IU/100 kcal) of vitamin A and vitamin E between milk- and soy-based formulas. When the mean vitamin A and vitamin E levels of formulas produced by the various firms were compared on an IU/100 kcal or percent of label declaration basis, significant differences (alpha = 0.05) were found among firms. Mean vitamin A levels for the various products compared to label declarations ranged from 126% of declared for the ready-to-use formulas to 139% of declared for the powders. Mean vitamin E levels ranged from 97% of declared for ready-to-use formulas to 118% of declared for concentrates. Except for one sample that contained 248 IU vitamin A/100 kcal, the formulas met the requirements of the 1980 Infant Formula Act. PMID- 4019377 TI - Atomic absorption spectrophotometric determination of cobalt in foods. AB - A method is described for the determination of cobalt in foods. After wet digestion, iron in the sample is removed by liquid-liquid extraction, and cobalt is isolated and extracted. Final determination is done by flame atomic absorption spectrophotometry. Analysis of NBS reference materials by this procedure gives results in close agreement with certified values. The limit of quantitation is 4.3 ng/mL. Recovery studies and analysis of standard materials show that this method is reliable. PMID- 4019378 TI - Liquid chromatographic determination of morphine sulfate and some contaminants in injections and bulk drug material. AB - A liquid chromatographic (LC) procedure is described for the assay of morphine sulfate in bulk drug material and injection solutions. The bulk drug and injection samples are prepared by direct dilution with LC mobile solvent. The average bulk drug purity (5 manufacturers) determined by the LC method was 99.9% with a difference of 0.1% from the average purity (anhydrous) found by the official USP XX procedure. The average LC recovery (19 studies) of morphine sulfate added to injection samples was 99.4% with a coefficient of variation (CV) of 1.14%. Morphine sulfate content was determined in triplicate for 53 injection samples (1-15 mg morphine sulfate/mL) formulated by 6 manufacturers, using the proposed LC procedure. Individual sample CV (n = 3) averaged 1.14%. The LC method is simple and specific for morphine sulfate. Major degradation products, preservatives, and some contaminants and related compounds are separated during LC. PMID- 4019379 TI - Rapid microchemical identification of four phenothiazine antiemetics with gold bromide and iodine-potassium iodide reagents: collaborative study. AB - A microchemical method was developed for the rapid identification of 4 phenothiazine antiemetics. Perphenazine, promethazine, thiethylperazine, and triflupromazine were positively identified and differentiated with the aid of a gold bromide reagent and an iodine-potassium iodide reagent. Only promethazine and triflupromazine yielded microcrystalline derivatives with gold bromide; only perphenazine and thiethylperazine reacted with iodine-potassium iodide. For each pair of positive reactions, the crystalline products were morphologically distinguishable under a microscope. The 2 tests were collaboratively studied by 7 independent laboratories and found to be simple, rapid, and effective for identifying the phenothiazines of interest. The method has been adopted official first action. PMID- 4019380 TI - Reverse phase liquid chromatographic determination of bisacodyl in dosage forms. AB - A method is described for the determination of bisacodyl in enteric-coated tablets and suppositories by liquid chromatography (LC). The method will also determine the hydrolysis degradation products monoacetylbisacodyl and desacetylbisacodyl. The sample is dissolved in 2-propanol, and the extract is diluted with the mobile phase and injected into a liquid chromatograph fitted with a mu Bondapak C18 column and an ultraviolet detector set at 254 nm. The column is eluted with methanol-acetonitrile-0.01M citric acid (25 + 25 + 50). The pooled mean recovery value for bisacodyl from commercial enteric-coated tablets and suppositories was 99.7% with a pooled coefficient of variation (CV) of 0.72%. For content uniformity assays, the CVs were 0.7 and 1.0% for groups of 10 individual commercial suppositories and tablets, respectively. Differences between assay values by the LC and USP XX methods were 0.2% of declared for enteric-coated tablets (n = 5) and 1.0% of declared for suppositories (n = 2). The LC method can determine as little as 0.015 microgram of the monoacetyl or desacetyl degradation product. PMID- 4019381 TI - DC polarographic assay of piperazines. AB - Piperazine, piperazine salts, and piperazine-containing compounds, e.g., diethylcarbamazine and piperazine theophylline, are determined by direct current polarography of the corresponding nitroso-derivative. The nitroso-derivative exhibits a well defined cathodic wave at -0.8 V vs SCE. The plot of peak height vs concentration is rectilinear between 1.6 X 10(-5) and 19.2 X 10(-5) M. Recoveries from bulk drugs were 97.7-101.12% with a standard deviation of 2.14 3.44. The procedure was successfully applied to analysis of drug content in representative dosage forms with good accuracy. PMID- 4019382 TI - Quantitation of indomethacin, naproxen, and ibuprofen in pharmaceutical dosage forms by first and second derivative ultraviolet spectrometry. AB - First and second derivative ultraviolet spectrometric methods are described for the estimation of indomethacin, naproxen, and ibuprofen in pharmaceutical dosage forms. The proposed methods permit the rapid, precise, and accurate determination of indomethacin capsules BP, naproxen capsules, and ibuprofen tablets BP. Matrix interference is successfully corrected. The results obtained by first and second derivative techniques are in accord with those obtained by the official assay method. PMID- 4019383 TI - Liquid chromatographic determination of organic nitrogenous bases in dosage forms: a progress report. AB - A liquid chromatographic (LC) method has been developed as a general procedure for the assay of the salts of organic nitrogenous bases in a variety of dosage forms. The method uses a nitrile-bonded reverse phase column, a methanol-0.003M ammonium acetate (90 + 10) mobile phase, and photometric detection at 254 nm. The sample is dissolved in the mobile phase and an aliquot is injected through a 20 microL injection loop. Average recovery values for duplicate assays were chlorpheniramine maleate injection 97.8%, chlorpheniramine maleate tablets 99.1%, cyclizine hydrochloride tablets 100.0%, doxylamine succinate tablets 103.3%, mesoridazine besylate tablets 100.4%, pentazocine hydrochloride tablets 103.0%, promethazine hydrochloride injection 98.4%, protriptyline hydrochloride tablets 101.2%, pyrilamine maleate tablets 97.8%, pyrimethamine tablets 100.0%, tripelennamine citrate elixir 100.0%, and tripelennamine hydrochloride tablets 97.2%. Results by this method were in good agreement with those obtained by the USP XX method. This study, which is being continued, will be expanded to include additional drugs. PMID- 4019384 TI - Determination of reserpine in commercial tablets by liquid chromatography with fluorescence detection. AB - A procedure is presented for the determination of reserpine in commercial tablets by liquid chromatography (LC). The sample is extracted with methanol if only reserpine is present. If the sample contains other ingredients, CHCI3 is used for extraction from aqueous suspension; the CHCI3 is subsequently completely evaporated in the presence of methanol. For LC, a normal phase column, methanol as the eluting solvent, and a fluorometric detector are used. A recovery study indicated that no measurable degradation of reserpine occurs during evaporation of the CHCI3 extract. Several commercial tablets containing reserpine alone or in combination with other ingredients were analyzed by the proposed method, and the results were compared with those obtained by the current official USP methods for reserpine. PMID- 4019385 TI - Liquid chromatographic determination of diazepam in tablets: collaborative study. AB - A stability indicating liquid chromatographic method for the determination of diazepam in tablets was collaboratively studied by 6 laboratories. The method uses a C18 reverse phase column, a methanol-water mobile phase, p-tolualdehyde as the internal standard, and photometric detection at 254 nm. The collaborators were supplied with a synthetic tablet powder and 3 commercial tablet samples. The mean recovery of diazepam from the synthetic tablet powder was 100.2%. For all samples analyzed, the coefficient of variation was less than 1.5%. The method has been adopted official first action. PMID- 4019386 TI - Gas chromatographic method for determination of fenitrothion in technical and in emulsifiable concentrate and water-dispersible powder formulations: collaborative study. AB - A variety of column packings and internal standards were evaluated to determine the most satisfactory system to use in a gas chromatographic (GC) method for analysis of fenitrothion, technical and formulations. Fenitrothion and the most closely related isomer, O,O-dimethyl O-(4-methyl-3-nitrophenyl) phosphorothioate, were resolved on columns packed with OV-210 and with polyphenyl ether, 6-ring (PPE-6R). A method based on the separation of fenitrothion on a PPE-6R column with fluoranthene as internal standard was selected for use in a limited collaborative trial and later for use in a full-scale collaborative trial with 21 collaborators participating. Each collaborator was furnished matched pairs of samples of technical fenitrothion, emulsifiable concentrate, and water dispersible powder. The coefficients of variation (CV) for the paired samples were 1.02, 1.11, and 1.01, respectively, for technical fenitrothion, emulsifiable concentrates, and water-dispersible powders. Data are also presented for an alternative method in which compounds are separated on an OV-210 column with dibutyl sebacate as the internal standard. The method has been adopted official first action. PMID- 4019387 TI - Liquid chromatographic determination of nicarbazin in feed. AB - A liquid chromatographic method was developed for the determination of nicarbazin (4,4'-dinitrocarbanilide.2-hydroxy-4,6-dimethylpyrimidine) in chicken feed. Ground feed was extracted with hot dimethylformamide, filtered, and then cleaned up on an alumina column. The nicarbazin was eluted from the column with ethanol and quantitated using a reverse phase C-18 column, with a methanol-water mobile phase and ultraviolet detection at 344 nm. Recoveries at a typical use level of 100 micrograms/g feed averaged 98% with a standard deviation of 3%. Samples fortified at levels as low as 0.1 micrograms/g were analyzed with 92% recovery. The detection limit is 1 ng, and the response is linear between 4 and 1000 ng. Feed additives in combination with nicarbazin do not interfere with recovery. PMID- 4019388 TI - Liquid chromatographic determination of morantel tartrate in cattle feed. AB - A liquid chromatographic (LC) method is proposed for measuring 0.485-0.970% morantel tartrate in cattle feeds. The drug is leached from feed, diluted, separated from interfering substances on a silica column, and measured in the effluent stream by 313 nm spectrophotometric detection. Two potential degradation products, i.e., cis-isomer of morantel tartrate and N-(3-methylaminopropyl)-trans 3-(3-methyl-2-thienyl)acrylamide, and a related anthelmintic, i.e., pyrantel tartrate, do not interfere. Average recovery of drug from liquid spiked samples and laboratory blends was 98-100% with a maximum coefficient of variation (CV) of 2.3%. Results for pelleted and crumbled commercial scale feeds ranged from 94 to 102% of label claim, with a maximum CV of 1.5%. PMID- 4019389 TI - Improved cleanup for gas chromatographic determination of propiconazole residues in soil, wheat grain, straw, and leaves. AB - A simple and sensitive method is described for determination of propiconazole, a new type of broad-spectrum systemic fungicide, in soil, wheat grain, straw, and leaves. Pesticide residues in or on grain and green plant materials are extracted with methanol (or a mixture of methanol and water (4 + 1), for soil), partitioned into methylene chloride, and cleaned up on an alumina column for grain and soil or an activated charcoal column for green plant materials. The amount of residue is quantitatively measured by gas chromatography using an alkali flame ionization detector in the nitrogen-sensitive mode. Recoveries from soil, grain, and green plant materials fortified at 0.1-5 mg/kg are better than 80%. The practical detection limits of this method are 0.01 mg/kg in grain and soil and 0.02 mg/kg in green plant materials. PMID- 4019390 TI - Improved procedure for determination of acrylonitrile in foods and its application to meat. AB - The previously described headspace-gas chromatographic procedure for the determination of acrylonitrile (AN) in several foods, with N/P selective detection, has been modified to include packaged luncheon meats. The loss of AN during equilibration at 100 degrees C in meat samples as well as the previously described loss in cold pack cheese and peanut butter has been studied. The loss of AN could be prevented by the addition of 10% phosphoric acid, which increases the acidity of the food-acid-salt slurry to pH 1.2-1.5. This acidification permits detection of AN at 2 ppb (5% FSD at 16 X 10(-2) amp/mV) in all foods studied. AN was not detected in 10 samples of luncheon meat packaged in AN-based plastic which contained up to 2.6 ppm AN. PMID- 4019391 TI - Treatment of a patient with chronic bronchial asthma with many bronchoscopies and lavages using acetylcysteine: a case report. AB - This Case Report is that of a young woman followed for 21 years, whose life was saved repeatedly by bronchoscopy and lavage to remove mucous plugs and casts from the tracheobronchial tree. In 1982, after again having a respiratory crisis and not having a bronchoscopy and lavage, she died. The pathology revealed a thickened hyalinized basement membrane and numerous mucous plugs filling the larger bronchi and bronchioles. PMID- 4019392 TI - Childhood asthma hospitalization rates in Spokane County, Washington: impact of volcanic ash air pollution. PMID- 4019393 TI - Vegan regimen with reduced medication in the treatment of bronchial asthma. AB - Thirty-five patients who had suffered from bronchial asthma for an average of 12 yr, all receiving long-term medication, 20 including cortisone, were subject to therapy with vegan food for 1 yr. In almost all cases, medication was withdrawn or drastically reduced. There was a significant decrease in asthma symptoms. Twenty-four patients (69%) fulfilled the treatment. Of these, 71% reported improvement at 4 months and 92% at 1 yr. There was a significant improvement in a number of clinical variables; for example, vital capacity, forced expiratory volume at one sec and physical working capacity, as well as a significant change in various biochemical indices as haptoglobin, IgM, IgE, cholesterol, and triglycerides in blood. Selected patients, with a fear of side-effects of medication, who are interested in alternative health care, might get well and replace conventional medication with this regimen. PMID- 4019394 TI - Re: "Great Expectations" versus immunotherapy. PMID- 4019395 TI - Re: Food allergy. PMID- 4019396 TI - Decreased theophylline clearance causing toxicity in children during viral epidemics. PMID- 4019397 TI - Interpretation of bronchodilator response and the prescription of bronchodilators: the equivalent of tossing coins? PMID- 4019398 TI - Gaonkar's maneuver for treating allergic asthma, allergic rhinitis, and chronic sinusitis. PMID- 4019399 TI - Family constellations in relation to asthma. PMID- 4019400 TI - The problem of mucus plugging in children with asthma. AB - The problem of mucus plugging of the lung was evaluated in 73 asthmatic children who had suffered a total of 187 episodes. The condition presented in young children, mostly with severe asthma, without any specific precipitating factor other than a severe attack of wheezing. Multiple lobe involvement was common, and the right lung was most often affected. Bronchoscopy was unnecessary but chest physiotherapy was found to be useful in the treatment of this complication of asthma. PMID- 4019401 TI - [Initial computed tomographic evaluation of multiple injuries. Personal experience and review of the literature]. PMID- 4019402 TI - Computerised tomography in fractures of the acetabulum, does it surpass conventional radiography? PMID- 4019403 TI - [Traumatic lesions of the thoracic aorta: angiography, a crucial examination]. PMID- 4019404 TI - [Conventional radiology and thoracic injuries]. PMID- 4019405 TI - Chance's fracture. PMID- 4019406 TI - [Computed tomography of thoraco-abdominal injuries]. PMID- 4019407 TI - Chemotaxis to aromatic and hydroaromatic acids: comparison of Bradyrhizobium japonicum and Rhizobium trifolii. AB - Rhizobia are bacteria well known for their ability to fix nitrogen in symbiosis with leguminous plants. Members of diverse rhizobial species grow at the expense of hydroaromatic and aromatic compounds commonly found in plant cells and plant litter. Using a quantitative capillary assay to measure chemotaxis, we tested the ability of hydroaromatic acids, selected aromatic acids, and their metabolites to serve as chemoattractants for two distantly related rhizobial species, Bradyrhizobium japonicum and Rhizobium trifolii. Slow-growing B. japonicum I-110 demonstrated positive chemotaxis to shikimate, quinate, protocatechuate, and vanillate; threshold concentrations for the compounds were as low as 10(-6) M. The dicarboxylic acids succinate and beta-ketoadipate, metabolites in the catabolism of many aromatic compounds, were positive chemoattractants with low threshold concentrations as well. Taxis to beta-ketoadipate occurred constitutively and, of the tested compounds, beta-ketoadipate gave the strongest peak response. Taxis to shikimate or quinate was induced by growth on either substrate but not by growth on protocatechuate or succinate. In contrast, fast growing R. trifolii 2066 was only weakly attracted to quinate and other aromatic and dicarboxylic acids that were strong attractants for B. japonicum. The R. trifolii strain exhibited positive chemotaxis to shikimate, but the threshold concentration of shikimate required to elicit a response (10(-4) M) was 2 orders of magnitude higher than that for the B. japonicum strain. PMID- 4019408 TI - H2-dependent mixotrophic growth of N2-fixing Azotobacter vinelandii. AB - Azotobacter vinelandii can grow with a variety of organic carbon sources and fix N2 without the need for added H2. However, due to an active H2-oxidizing system, H2-dependent mixotrophic growth in an N-free medium was demonstrated when mannose was provided as the carbon source. There was no appreciable growth with either H2 or mannose alone. Both the growth rate and the cell yield were dependent on the concentrations of both substrates, H2 and mannose. Cultures growing mixotrophically with H2 and mannose consumed approximately 4.8 mmol of O2 and produced 4.6 mmol of CO2 per mmol of mannose consumed. In the absence of H2, less CO2 was produced, less O2 was consumed, and cell growth was negligible. The rate of acetylene reduction in mixotrophic cultures was comparable to the rate in cultures grown in N-free sucrose medium. The rate of [14C]mannose uptake of cultures with H2 was greater than with argon, whereas [14C]sucrose uptake was unaffected by the addition of H2; therefore, the role of H2 in mixotrophic metabolism may be to provide energy for mannose uptake. A. vinelandii is not an autotroph, as attempts to grow the organism chemoautotrophically with H2 or to detect ribulose bisphosphate carboxylase activity were unsuccessful. PMID- 4019409 TI - Organization and distribution of the cellulosome in Clostridium thermocellum. AB - The properties of the cellulosome (the cellulose-binding, multicellulase containing protein complex) in Clostridium thermocellum were examined by comparing the cellulase systems derived from the wild type and an adherence defective mutant. The growth conditions--specifically, growth either on cellulose (Avicel) or on cellobiose as insoluble or soluble carbon sources, respectively- were found to be critical to the distribution of the cellulosome in the mutant system: the cellobiose-grown mutant (in contrast to the wild type) lacked the cellulosome on its surface and produced only minor quantities of the extracellular cellulosome accompanied by other relatively low-molecular-weight cellulases. The polypeptide composition of the respective purified cellulosome was dependent on the nature of the carbon source and was similar for both wild type and mutant cells. Ultrastructural analysis revealed the presence of novel polycellulosomal protuberances on the cell surface of the cellobiose-grown wild type which were absent in the mutant. PMID- 4019410 TI - Bdellovibrio bacteriovorus synthesizes an OmpF-like outer membrane protein during both axenic and intraperiplasmic growth. AB - Outer membrane preparations of Bdellovibrio bacteriovorus grown intraperiplasmically on Escherichia coli containing OmpF were prepared by the Triton X-100 procedure of Schnaitman (J. Bacteriol. 108:545-552, 1971). They contained a protein that migrated to almost the same position as E. coli OmpF in sodium dodecyl sulfate-acrylamide gradient gel electrophoresis and to the same position as E. coli OmpF when urea was incorporated into the gel. The mobility of this protein increased relative to that of OmpC in urea-containing gels as does E. coli OmpF. However, the same protein was also produced during axenic growth and during intraperiplasmic growth on prey lacking OmpF. The peptide profile generated by partial proteolysis of this protein showed no homology to that produced from E. coli OmpF. We conclude that B. bacteriovorus synthesizes an OmpF like protein. Previous claims that the bdellovibrio incorporates an intact E. coli OmpF are not consistent with these observations. PMID- 4019411 TI - Purification and characterization of hydrolytic haloalkane dehalogenase from Xanthobacter autotrophicus GJ10. AB - A new enzyme, haloalkane dehalogenase, was isolated from the 1,2-dichloroethane utilizing bacterium Xanthobacter autotrophicus GJ10. The purified enzyme catalyzed the hydrolytic dehalogenation of n-halogenated C1 to C4 alkanes, including chlorinated, brominated, and iodinated compounds. The highest activity was found with 1,2-dichloroethane, 1,3-dichloropropane, and 1,2-dibromoethane. The enzyme followed Michaelis-Menten kinetics, and the Km for 1,2-dichloroethane was 1.1 mM. Maximum activity was found at pH 8.2 and 37 degrees C. Thiol reagents such as p-chloromercuribenzoate and iodoacetamide rapidly inhibited the enzyme. The protein consists of a single polypeptide chain of a molecular weight of 36,000, and its amino acid composition and N-terminal sequence are given. PMID- 4019412 TI - Purification and characterization of glutamate synthase from Azospirillum brasilense. AB - Growth conditions for Azospirillum brasilense Sp6 were devised for maximal expression of glutamate synthase. The enzyme levels were largely affected by the type and concentration of the nitrogen source. A 10-fold increase in the synthesis of the enzyme was observed at a limiting concentration of ammonia. The enzyme was purified to homogeneity by a procedure which was fairly rapid and allowed a good recovery of enzyme (30%). Azospirillum glutamate synthase is a complex iron-sulfur flavoprotein with a stoichiometry of 1 flavin adenine dinucleotide:1 flavin mononucleotide:8 Fe:8 S per protomer with a molecular weight of 185,000. The protomer is composed of two dissimilar subunits with molecular weights of 135,000 and 50,000. Kinetic parameters were determined. Km values for NADPH, 2-oxoglutarate, and L-glutamine were 6.25, 29, and 450 microM, respectively. The optimum pH was about 7.5. Complete reduction of the enzyme under anaerobic conditions was obtained either by NADPH (in the presence of a regenerating system) or dithionite or by photochemical reduction (in the presence of EDTA and 5-deazariboflavin). No stable long-wavelength intermediates were observed. PMID- 4019413 TI - Protoplast water content of bacterial spores determined by buoyant density sedimentation. AB - Protoplast wet densities (1.315 to 1.400 g/ml), determined by buoyant density sedimentation in Metrizamide gradients, were correlated inversely with the protoplast water contents (26.4 to 55.0 g of water/100 g of wet protoplast) of nine diverse types of pure lysozyme-sensitive dormant bacterial spores. The correlation equation provided a precise method for obtaining the protoplast water contents of other spore types with small impure samples and indicated that the average protoplast dry density was 1.460 g/ml. PMID- 4019414 TI - Evidence for two restriction-modification systems in Halobacterium cutirubrum. AB - Data from plating experiments indicated that Halobacterium cutirubrum NRC34001 has at least two separate restriction-modification systems. A spontaneous or induced loss of one or both systems resulted in four restriction-modification phenotypes. There was a positive correlation between changes in gas vacuolation phenotypes and either restriction-modification system. PMID- 4019415 TI - Localization of the enantiozymes of 6-hydroxy-nicotine oxidase in Arthrobacter oxidans by electron immunochemistry. AB - During the course of growth of Arthrobacter oxidans, induction of the enantiozymes 6-hydroxy-D-nicotine oxidase and 6-hydroxy-L-nicotine oxidase occurred in the presence of DL-nicotine. Cryoultramicrotomed sections obtained from cells grown to stationary phase were gold immunolabeled. The results obtained demonstrate that both enzymes are localized in the cytoplasm. PMID- 4019416 TI - Different staphylococcal species contain various numbers of penicillin-binding proteins ranging from four (Staphylococcus aureus) to only one (Staphylococcus hyicus). AB - The penicillin-binding proteins of a total of 25 staphylococcal strains belonging to five different species were analyzed. All strains of the same species showed an identical penicillin-binding protein pattern which clearly differed from that of strains of the other species. Staphylococcus aureus, Staphylococcus intermedius, Staphylococcus simulans, and the dolphin strains were found to contain two to four penicillin-binding proteins. Strains of Staphylococcus hyicus exhibited only one penicillin-binding protein. PMID- 4019417 TI - Glutathione-independent maleylacetoacetate isomerase in gram-positive bacteria. AB - Nocardia globerula CL1 produced a glutathione-independent maleylacetoacetate isomerase after growth on L-tyrosine. Partial purification of this isomerase demonstrated its independence of low-molecular-weight cofactors such as glutathione. Similar glutathione-independent maleylacetoacetate isomerases were present in three other gram-positive bacteria grown on tyrosine. PMID- 4019418 TI - Expression of Rhizobium trifolii early nodulation genes on maize and rice plants. AB - An IncQ multicopy vector (pKT230) and an IncP1 low-copy-number vector (pRK290), both carrying Rhizobium trifolii root hair curling (Hac) genes, were transferred to a Sym plasmid-cured derivative of R. trifolii ANU843. The resulting transconjugants were used to inoculate the monocotyledonous plants sorghum, maize, rice, and wheat. Transconjugants carrying the Hac genes on the multicopy vector caused a root hair curling response on maize and rice plants 14 days after inoculation. PMID- 4019419 TI - Family history of suicide in affective disorder patients. AB - In a consecutive series of 137 affective disorder patients with a family history of suicide, bipolar disorder formed the biggest group. Of the 137 patients, 61 (44.5%) had made a total of 117 attempts at suicide. The patients who had attempted suicide, compared with those who had not, had a significantly earlier age of onset and longer duration of illness, and more of them were unmarried. PMID- 4019420 TI - The discriminate validity of the Psychiatric Diagnostic Interview. AB - The discriminate validity of the Psychiatric Diagnostic Interview (PDI), a criterion-referenced, structured diagnostic instrument, is discussed. Data presented indicate that the PDI has an acceptable level of discriminate ability, making it a useful screening tool for detecting a variety of well-defined psychiatric disorders. PMID- 4019421 TI - Treatment responses in primary and secondary melancholia: a preliminary report. AB - Ten patients suffering from primary affective illness and melancholia were compared to 10 melancholic subjects whose depression was chronologically superimposed on a preexisting nonaffective psychiatric disturbance. Both groups displayed a satisfactory response to treatment with amitriptyline. Similar patterns of improvement were reported in the two groups, and there was a concordance of subjective and objective rating methods. PMID- 4019422 TI - Depression after minor closed head injury: role of dexamethasone suppression test and antidepressants. AB - The results of dexamethasone suppression test (DST) and the effectiveness of amitriptyline and phenelzine in treating depression with melancholia after minor closed head injury in 10 patients were compared to those in 12 control patients with primary depression and melancholia. Prevalence of abnormal DST results was higher in the control group (91%) than in the closed head injury group (10%). Results of the DST corresponded with clinical improvement. Amitriptyline produced significant and consistent improvement in all control patients at the end of 4 weeks of treatment. No patient in the closed head injury group showed significant improvement with amitriptyline. The closed head injury patients were treated with phenelzine after a 3- to 7-day washout period. No statistical improvement after 4 weeks of treatment with phenelzine was seen in any of these patients. The DST may be useful as an adjunct to the diagnostic and monitoring process in primary depression with melancholia. Depression after minor closed head injury did not correlate with the DST. Amitriptyline and phenelzine have limited use (if any) in depression with melancholia after minor closed head injury. PMID- 4019423 TI - Drug abuse among state hospital psychiatric inpatients with particular reference to PCP. AB - The pattern of alcohol and drug abuse among 78 consecutive newly admitted patients to a middle Tennessee state hospital psychiatric ward was examined. There was a high prevalence of alcohol, marijuana, hypnotic sedative, and stimulant abuse among this patient population within 1 month prior to their hospitalization. However, only 1 patient gave a history of PCP abuse and none of the 76 plasma samples analyzed by the GCN and GC2-N methods was positive for PCP or its common analogues. This study does not support a high prevalence of PCP abuse among this group of psychiatric patients. PMID- 4019424 TI - Homicidality in a woman with a 47,XXX karyotype. AB - The 47,XXX karyotype is a rare sex chromosome anomaly. A female with this karyotype is called a triple X or superfemale. This karyotype is usually not associated with a characteristic mental or physical phenotype. A 19-year-old female who committed homicide and was found to have a 47,XXX karyotype is described, and the possible correlation between sex chromosome anomalies and psychopathology or criminality is discussed. PMID- 4019425 TI - Schizophreniform psychosis associated with chronic industrial toluene exposure: case report. AB - Toluene is a solvent commonly used in the workplace and, in the last 25 years, it has gained notoriety as a substance of abuse. The central nervous system sequelae of both occupational and illicit exposure to toluene have been documented, and irreversible cerebellar changes have been described. Previous reports of psychosis associated with toluene have emphasized its reversibility. We report a case of an irreversible schizophreniform psychosis associated with 5 years of continuous occupational exposure to toluene. PMID- 4019426 TI - Lithium neurotoxicity in patients with degenerative brain disease. PMID- 4019428 TI - Anorexia nervosa in a 45-year-old man. PMID- 4019427 TI - Androgen-induced hypomania. PMID- 4019429 TI - L-phenylalanine. PMID- 4019430 TI - Studies on specific intercellular adhesion. PMID- 4019431 TI - Long term oscillation in glycolysis. AB - To increase the period of glycolytic oscillations in yeast extracts (Saccharomyces uvarum), the dependence of the period on pH, on concentrations of phosphate and enzymes, and on temperature has been studied. Stable oscillatory trans were obtained at a pH value of about 6.5. Increasing the phosphate and decreasing the enzyme concentrations as well as decreasing temperature lengthened the period. By dilution of the extract with buffer while maintaining the metabolite concentrations at their initial level the period could be successively prolonged from 20 min to about 6 h. PMID- 4019432 TI - The role of albumin in the hepatic transport of bilirubin: studies in mutant analbuminemic rats. AB - Bilirubin and other cholephilic organic anions are bound to albumin in the circulation; their hepatic uptake involves a carrier-mediated process. To investigate the possible role of serum albumin in the transhepatic transport of a cholephilic ligand, plasma clearance of radioactive bilirubin and its biliary excretion as well as its interaction with plasma proteins were compared between normal and mutant analbuminemic rats (NAR). With a tracer amount of 3H-labeled bilirubin, its plasma clearance and biliary excretion were comparable in both animal groups. However, the plasma clearance of a loading dose of the ligand was significantly increased and its biliary recovery was low in NAR as compared with normal animals. In accord with these findings in vivo, gel permeation chromatographic analysis revealed that the bilirubin binding capacity of serum proteins was significantly lower in NAR than in control animals. When bilirubin was administered to NAR as a mixture with equimolar albumin, its plasma disappearance was considerably decreased and its biliary recovery was increased. Similar effects were observed when albumin was replaced by an equimolar amount of glutathione S-transferases (ligandins). These observations indicate that, although ligand-protein interaction in the circulation is important for directing bilirubin to the plasma membranes of the hepatocyte, this mechanism is not specific for albumin. PMID- 4019433 TI - Subterminal hydroxylation of fatty acids by a cytochrome P-450-dependent enzyme system from a fungus, Fusarium oxysporum. AB - The cell-free extract of a cytochrome P-450-producing fungus, Fusarium oxysporum, was found to catalyze the hydroxylation of fatty acids. Three product isomers were formed from a single fatty acid. The products from lauric acid were identified by mass-spectrometry as 9-, 10-, and 11-hydroxydodecanoic acids, and those from palmitic acid as 13-, 14-, and 15-hydroxyhexadecanoic acids. The ratio of the isomers formed was 50 : 36 : 14 in the case of laurate hydroxylation, and 37 : 47 : 16 in the case of palmitate. The reaction was dependent on both NADPH (or NADH) and molecular oxygen,and was strongly inhibited by carbon monoxide, menadione, or the antibody to purified Fusarium P-450. Further, lauric acid induced a type I spectral change in purified Fusarium P-450. Further, lauric acid induced a type I spectral change in purified Fusarium P-450 with an apparent Kd of 0.3 mM. The hydroxylase activity together with cytochrome P-450 could be detected in both the soluble and microsome fractions, and the activity was almost proportional to the amount of cytochrome P-450 reducible with NADPH. It can be concluded from these results that Fusarium P-450 reducible with NADPH. It can be concluded from these results that Fusarium P-450 is involved in the (omega-1)-, (omega-2)-, and (omega-3)-hydroxylation of fatty acids catalyzed by the cell-free extract of the fungus. PMID- 4019434 TI - Lipid composition of the plasma membrane isolated from hyperplastic nodules of rat liver. AB - Hyperplastic nodules and hepatomas were induced in livers of rats fed a diet containing 0.05% N-2-fluorenylacetamide (2-FAA). The lipid contents, and phospholipid and fatty acid compositions were analyzed in plasma membranes (PM's) isolated from these tissues and normal rat liver, and the following trends were observed. The molar ratio of cholesterol to phospholipid-phosphorus (phospholipid P) increased in the order: hepatoma less than normal liver less than hyperplastic nodules. The molar percentage of plasmalogen to phospholipid-P decreased in the order: hepatoma = hyperplastic nodules greater than normal liver. The percentages of choline phosphoglycerides (sum of phosphatidylcholine and lysophosphatidylcholine) and ethanolamine phosphoglycerides (sum of phosphatidylethanolamine and lysophosphatidylethanolamine) both decreased in the order: hepatoma greater than hyperplastic nodules greater than normal liver. On the other hand, the percentages of sphingomyelin and phosphatidylserine both increased in the order: hepatoma less than hyperplastic nodules less than normal liver. As regards fatty acid composition, the percentages of both 18:1 and 18:2 decreased in the order: hepatoma greater than hyperplastic nodules greater than normal liver. Those of 18:0 and 20:4 increased in the order: hepatoma less than hyperplastic nodules less than normal liver. These results suggested that the lipid bilayer in PM of hyperplastic nodules has characteristics roughly intermediate between those of hepatoma and liver PM's, although the molar ratio of cholesterol to phospholipid-P in hyperplastic nodules PM was not intermediate. PMID- 4019435 TI - Isolation and characterization of a lectin from the fruit of Clerodendron trichotomum. AB - An agglutinin of Clerodendron trichotomum fruit (CTA), found to be specific for N acetyl-D-galactosamine and D-galactose, was isolated and characterized. The fruit extract was decolorized first by passage through a Toyopearl column and a phenyl Sepharose column. Then the lectin activity was adsorbed on p-aminophenyl N-acetyl alpha-D-galactosaminide- or p-aminophenyl beta-D-galactoside-Sepharose, and eluted as a sharp peak with 0.2 M lactose. The purified CTA was found to be homogeneous by SDS-polyacrylamide gel electrophoresis, gel chromatography and ultracentrifugal analysis, and was determined to be a glycoprotein homodimer with a molecular weight of 56,000 daltons. Hemagglutination-inhibition assay indicated that CTA is most specific for N-acetyl-D-galactosaminide with a hydrophobic aglycon. PMID- 4019436 TI - A novel enzyme producing isoprimeverose from oligoxyloglucans of Aspergillus oryzae. AB - An enzyme producing isoprimeverose from xyloglucan fragment oligosaccharides has been purified to the electrophoretically pure state from a commercial enzyme preparation of Aspergillus oryzae (Sanzyme 1000). The purified enzyme showed approximately 1,280-fold increase of the specific activity over the original preparation. The purified enzyme was shown to be an oligomeric protein consisting of two subunits, each of which had a molecular weight of 115,000. The enzyme showed the highest activity at pH 5.0 and 60 degrees C, and was stable in the pH range from 5 to 7 and at up to 50 degrees C. The isoelectric point of this enzyme was pH 3.9. The purified enzyme was highly specific for xyloglucan fragment oligosaccharides and split off isoprimeverose units from the non-reducing end of the backbone of the substrate. PMID- 4019437 TI - Studies on the metabolism of unsaturated fatty acids. XVI. Purification and general properties of 2,4-dienoyl-CoA reductase from Candida lipolytica. AB - 2,4-Dienoyl-CoA reductase has been purified to homogeneity from Candida lipolytica cultivated in the presence of linoleic acid. The native enzyme had a molecular weight close to 360,000 as estimated by gel filtration on Sepharose CL 4B, whereas the subunit molecular weight estimated by sodium dodecyl sulfate polyacrylamide gel electrophoresis was 33,000. The purified 2,4-dienoyl-CoA reductase from C. lipolytica gave a single precipitin line with antibodies raised against the purified enzyme from C. lipolytica. The general properties of the 2,4 dienyl-CoA reductase from C. lipolytica were examined. The enzyme had optimal pH at 6.5 and was inactivated by heat treatment at 50 degrees C for 10 min. trans 2,trans-4-Octadienoyl-CoA was the most active substrate of the dienoyl-CoA esters examined. PMID- 4019438 TI - Assay of fatty acid synthetase by mass fragmentography using [13C]malonyl-CoA. AB - A new assay method for fatty acid synthetase using mass fragmentography was described. [2-13C]Malonyl-CoA was chemically synthesized from [2-13C]malonic acid and used as a substrate. The newly synthesized fatty acids were quantitated with a GC-MS instrument after methyl esterification. Monitoring of molecular ions of the newly synthesized fatty acids enabled us to determine the absolute amounts with heptadecanoic acid as an internal standard. Multiple products (14 : 0, 16 : 0, and 18 : 0) were measured individually. Using this technique, we obtained information about production profiles such as that of chain length against incubation temperature and about malonyl-CoA decarboxylation activity in enzyme preparations, and we also confirmed the presence of malonyl-CoA decarboxylation activity even in purified fatty acid synthetase from guinea pig Harderian gland. Compared with the conventional assay methods (spectrophotometric and radioisotopic), this method was more reliable and useful. PMID- 4019439 TI - Purification and some properties of rabbit liver cytosol thioltransferase. AB - Thioltransferase was purified 650-fold from rabbit liver by procedures including acid treatment, heat treatment, gel filtration on Sephadex G-50, column chromatography on DEAE-cellulose, isoelectric focusing (pH 3.5-10) and gel filtration on Sephadex G-75. The final enzyme preparation was almost homogeneous in polyacrylamide gel electrophoretic analysis. Only one active peak with an apparent molecular weight (Mr) of 13,000 was detected by gel filtration on Sephadex G-50 and only a single protein band with a molecular weight of 12,400 was detected by sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis. Isoelectric focusing revealed only one enzyme species, having an isoelectric point (pI) of 5.3. The enzyme has an optimum pH about 3.0 with S-sulfocysteine and GSH as substrates. The purified enzyme utilized some disulfides including S sulfocysteine, alpha-chymotrypsin, trypsin, bovine serum albumin, and insulin as substrates in the presence of GSH. The enzyme does not act as a protein : disulfide isomerase (the activity of which can be measured in terms of reactivation of randomly reoxidized soybean Kunitz trypsin inhibitor). The enzyme activity was inhibited by chloramphenicol, but not by bacitracin. The inhibition by chloramphenicol was non-competitive (apparent K1 of 0.5 mM). Thioltransferase activity was found in the cytosol of various rabbit tissues. PMID- 4019440 TI - Fructose 1,6-bisphosphate-dependent L-lactate dehydrogenase from Thermus aquaticus YT-1, an extreme thermophile: activation by citrate and modification reagents and comparison with Thermus caldophilus GK24 L-lactate dehydrogenase. AB - Heat-stable fructose 1,6-bisphosphate-dependent L-lactate dehydrogenase [EC 1.1.1.27] was purified from an extremely thermophilic bacterium, Thermus aquaticus YT-1. The amino acid composition and NH2-terminal 34 amino acid sequence of the enzyme were determined. Its NH2-terminal sequence shows high homology with those of Thermus caldophilus GK24 (82% identity) and some other bacterial L-lactate dehydrogenases (44-53% identity), indicating the close phylogenic relationship of the two Thermus species. At the same time, the two Thermus L-lactate dehydrogenases were found not to be identical not only chemically but also kinetically and immunologically. Citrate activated the T. aquaticus enzyme in the weak acidic pH region, while fructose 1,6-bisphosphate did in both acidic and neutral pH regions. The maximum activity obtained with citrate at pH 5.0 was about 2.5 times higher than that in the presence of fructose 1,6-bisphosphate at pH 6.7. The enzymes modified with 2,3-butanedione, acetic anhydride and diethyl pyrocarbonate in the presence of both NADH and oxamate were desensitized to fructose 1,6-bisphosphate, and the modified enzymes were active even in the absence of fructose 1,6-bisphosphate. All of the modified enzymes examined were still activated by citrate similarly to the native enzyme. These results suggest that the mechanism of activation by citrate is different from that by fructose 1,6-bisphosphate, and that the citrate-binding site is different from the fructose 1,6-bisphosphate-binding site. PMID- 4019441 TI - Partial purification and characterization of lathosterol 5-desaturase from rat liver microsomes. AB - The terminal oxidase of the NADH-dependent lathosterol 5-desaturation system was solubilized from rat liver microsomes with 2% Triton X-100, and partially purified approximately 18-fold with 19% yield after DEAE-cellulose and 6 aminohexyl-Sepharose column chromatography. The final enzyme preparation was free from other electron transfer components and phospholipids in microsomes, and the desaturation reaction was reconstituted with the following components: NADH, molecular oxygen, phospholipids and three proteins, i.e., NADH-cytochrome b5 reductase, cytochrome b5 and the terminal oxidase. Omission of one of these components led to an almost complete loss of the desaturase activity. Under the reconstitution conditions, the desaturase activity was significantly inhibited by potassium cyanide but was not affected by -SH reagents such as N-ethylmaleimide and dithiothreitol. PMID- 4019442 TI - Bioactive gangliosides. IV. Ganglioside GQ1b/Ca2+ dependent protein kinase activity exists in the plasma membrane fraction of neuroblastoma cell line, GOTO. AB - A ganglioside-stimulated protein phosphorylation system was discovered in plasma membrane fractions of human neuroblastoma cells (GOTO). Gangliosides (GQ1b, GT1a, GT1b, GD1a, GD1b, GD3, and GM1) could stimulate this system. GQ1b showed the most effective stimulation among these gangliosides. The substrate specificity was rather broad. Not only some (de novo) proteins of the membranes but also purified histones and tubulin were phosphate-acceptable. This protein phosphorylation system specifically depended upon Ca2+ (optimum concentration: 50-100 microM). The optimum pH was 7.0-7.5. GQ1b/Ca2+ could not directly activate well known protein kinases (Ca2+/phospholipid-activated protein kinase, Ca2+/calmodulin activated protein kinase, and cyclic nucleotide-dependent protein kinases). Furthermore, GQ1b could replace neither phospholipids nor calmodulin. Thus, an unknown, new type of protein kinase(s) may be involved in this system. Alternatively, GQ1b may activate some known protein kinase(s) in cooperation with another unknown factor which may be removed during the preparation of the partially purified known protein kinase used in this experiment. PMID- 4019443 TI - Structural studies on the carbohydrate moieties of rat liver cathepsins B and H. AB - Cathepsins B and H from rat liver contain one asparagine-linked sugar chain in each molecule. The sugar chains were liberated from the polypeptide portions by hydrazinolysis followed by N-acetylation and NaB3H4 reduction. Paper electrophoresis of the radioactive oligosaccharide fractions revealed that they were mixtures of neutral oligosaccharides only. After fractionation by gel filtration the structure of each oligosaccharide was studied by sequential exoglycosidase digestion in combination with methylation analysis. The sugar chain of cathepsin H was a high mannose type oligosaccharide which varied in size from 5 to 9 mannose residues; on the other hand the major oligosaccharide of cathepsin B was a tetrasaccharide whose structure was Manalpha 1----6Manbeta 1--- 4GlcNAcbeta 1----4GlcNAc. PMID- 4019444 TI - Cell cycle-dependent regulation of eukaryotic DNA methylase level. AB - DNA methylase activity in the nuclei of somatic cells arrested at G0 increased markedly when the cells were subjected to a mitogenic stimulus. Treatment of mouse splenocytes with Concanavalin A resulted in about 20-fold increase in methylase activity within 20 h starting 12-15 h after Concanavalin A addition. The methylase level in rat liver was elevated approximately 3-fold at about 20-h posthepatectomy. A detailed time course of the increase in methylase activity with respect to the cell cycle revealed that the onset of this event coincided with the entry of the cells into S phase. In both systems, the extent of methylation in CpG sequences is not altered significantly even under conditions of active DNA synthesis which is induced by the mitogenic effect. These results suggest that the cell responds to the mitogenic stimulus by adjusting the DNA methylase activity to enable conservation of the methylation level in DNA. PMID- 4019445 TI - Decreased estrogenic stimulation of RNA polymerase II in aged rat uteri is apparently due to reduced nuclear binding of receptor-estradiol complexes. AB - The maximum ability of receptor-estradiol complexes to activate RNA polymerase II and bind to nuclear acceptor sites is reduced 40-50% in senescent rat uteri. A precise, linear stoichiometric relationship exists between acceptor site occupancy and polymerase activity, and this relationship is not altered with aging. Thus, reduced ability of estrogen to stimulate RNA polymerase II in aged rat uteri appears to be due to deficits in binding of receptor-estradiol complexes to nuclear acceptor sites. PMID- 4019446 TI - Effects of trifluoperazine on calcium binding by calmodulin. A microcalorimetric study. AB - Microcalorimetric titrations of calmodulin with Ca2+ and trifluoperazine (TFP) at various molar ratios have been carried out at 25 degrees C and at pH 7.0. Ca2+ binding to calmodulin produces heat (-delta H) in the presence of TFP, while heat is absorbed in the absence of TFP. The total heat produced by Ca2+ binding to all four sites is increased at increasing TFP-to-calmodulin ratios, attaining a plateau at about 7. These results indicate that at the higher ratios, the enthalpy changes (delta H) associated with Ca2+ binding are affected by TFP molecules bound at both high- and low-affinity sites. In addition, the Ca2+ binding reaction of the calmodulin-TFP complex is driven solely by a favorable enthalpy change of -27 kJ/mol of site; the entropy change (delta S) is -35 J/mol/K. These thermodynamic changes are opposite to those for TFP-free calmodulin and distinctly different from other Ca2+ binding proteins such as skeletal and cardiac troponin C and parvalbumin, where the reaction is driven by favorable changes of entropy as well as enthalpy. PMID- 4019447 TI - Interconversion of androgen receptor forms by divalent cations and 8 S androgen receptor-promoting factor. Effects of Zn2+, Cd2+, Ca2+, and Mg2+. AB - The effects of divalent cations (Zn2+, Cd2+, Ca2+, Mg2+) on the cytosol androgen receptor were determined by sedimentation into sucrose gradients. At low ionic strength (25 mM KCl, 50 mM Tris, pH 7.4), Zn2+ (200 microM total, which calculates to 130 nM free Zn2+ in 10 mM mercaptoethanol) causes a shift in the sedimentation coefficient of the rat Dunning prostate tumor (R3327H) cytosol receptor and rat ventral prostate cytosol receptor from 7.5 +/- 0.3 S to 8.6 +/- 0.3 S. Zn2+ stabilizes the 8.6 S receptor form in salt concentrations up to 0.15 M KCl in 50 mM Tris, pH 7.2. In low ionic strength gradients containing Ca2+ (greater than or equal to 200 microM) or Mg2+ (greater than or equal to 1 mM), the receptor sediments as 4.7 +/- 0.3 S. The dissociating effects of Ca2+ and Mg2+ can be fully reversed by sedimentation into gradients containing Zn2+ (200 microM total) or Cd2+ (10 microM total). In the presence of Zn2+ (200 microM total), Ca2+ (10 microM to 3 mM) converts the receptor to an intermediate form with sedimentation coefficient 6.2 +/- 0.2 S, Stokes radius 73 A, and apparent Mr approximately 203,000. The potentiating effect of Zn2+ on formation of the 8.6 S receptor (in the absence of Ca2+) and the 6.2 S receptor (in the presence of Ca2+) requires both the 4.5 S receptor and the 8 S androgen receptor-promoting factor. Sodium molybdate stabilizes the untransformed cytosol receptor but, unlike Zn2+, does not promote reconstitution of the 8.6 S receptor from its partially purified components. These results indicate that divalent cations alter the molecular size of the androgen receptor in vitro and thus may have a role in altering the state of transformation of the receptor. PMID- 4019448 TI - Amino acid sequence of the Anthopleura xanthogrammica heart stimulant, anthopleurin-B. AB - Anthopleurin-B, the most potent peptide heart stimulant from the sea anemone Anthopleura xanthogrammica, was shown to exist as a single polypeptide chain consisting of 49 amino acid residues. The sequence of the peptide was shown to be: Gly-Val-Pro-Cys-Leu-Cys-Asp-Ser-Asp-Gly- Pro-Arg-Pro-Arg-Gly-Asn-Thr-Leu-Ser Gly-Ile-Leu-Trp-Phe-Tyr-Pro-Ser- Gly-Cys-Pro-Ser-Gly-Trp-His-Asn-Cys-Lys-Ala-His Gly-Pro-Asn-Ile-Gly- Trp-Cys-Cys-Lys-Lys. The carboxymethylcysteine derivative, tryptic and chymotryptic peptides (obtained from the derivative and separated by high performance liquid chromatography) were sequenced by manual Edman degradation. Although six carboxymethylcysteine residues were formed by reduction and alkylation of the polypeptide, no cysteine residues were detectable in the native protein, indicating that there are three cystine residues in anthopleurin B. The amino acid sequence differs in 7 places from anthopleurin-A: at residues 3 (Pro for Ser), 12 (Arg for Ser), 13 (Pro for Val), 21 (Ile for Thr), 24 (Phe for Leu), 42 (Asn for Thr), and 49 (Lys for Gln). These differences are important since anthopleurin-B is about a 12.5-fold better heart stimulant than anthopleurin-A from A. xanthogrammica, anthopleurin-C from Anthopleura elegantissima, and toxin II from Anemonia sulcata. PMID- 4019449 TI - Independence of the domains of metallothionein in metal binding. AB - Mammalian metallothionein is a low molecular weight protein with two metal binding domains. To determine if metal binding in one domain affects binding in the other, we prepared peptides corresponding to the regions that enfold the two metal-thiolate clusters. Metal reconstitution studies of these peptides revealed stoichiometries of metal binding similar to those observed within the intact molecule. Thus, the alpha domain coordinates 4 Cd(II), 6 Cu(I), or 6 Ag(I) ions regardless of whether the domain is part of the total protein or is studied as a separate peptide. Likewise, the beta domain binds 3 Cd(II), 6 Cu(I), or 6 Ag(I) ions in both the intact protein and as a separate peptide. If cluster B in intact metallothionein is preformed with Cu(I) or Ag(I), cluster A saturates with either 4 mol eq of Cd(II) or 6 mol eq of Ag(I). Similarly, preformation of the A cluster with Cd(II) does not affect the binding of 6 Cu(I) ions in the B cluster. Therefore, the metal-dependent folding of the protein to create one cluster occurs independent of constraints or influences from the other domain. Formation of the protein with a tetrahedrally coordinated metal in one cluster and a trigonally coordinated metal in the other center is possible. PMID- 4019450 TI - The obligatory intermediacy of 16,17 alpha- and 16,17 beta-epoxides in the biotransformation of androsta-5,16-dien-3 beta-ol to androst-5-ene-3 beta, 16 alpha, 17 beta- and -3 beta, 16 beta, 17 alpha-triols by male rat liver microsomes. AB - The C16-double bond of the biolefinic steroid, androsta-5,16-dien-3 beta-ol (delta 16-ANDO), was regioselectively oxidized by male rat liver microsomes in the presence of NADPH and EDTA to 16 alpha, 17 alpha-epoxyandrost-5-en-3 beta-ol (delta 16-ANDO 16,17 alpha-epoxide), 16 beta,-17 beta-epoxyandrost-5-en-3 beta-ol (delta 16-ANDO 16,17 beta-epoxide), androst-5-ene-3 beta, 16 alpha, 17 beta-triol (delta 16-ANDO 16 alpha, 17 beta-glycol), and androst-5-ene-3 beta, 16 beta, 17 alpha-triol (delta 16-ANDO 16 beta, 17 alpha-glycol). The microsomes hydrolyzed delta 16-ANDO 16,17 alpha-epoxide specifically to the 16 beta, 17 alpha-glycol and delta 16-ANDO 16,17 beta-epoxide to the 16 beta, 17 alpha-glycol and the 16 alpha, 17 beta-glycol in an equal ratio. delta 16-ANDO 16,17 alpha-epoxide was much more susceptible to microsomal hydrolysis than the 16,17 beta-epoxide. The xenobiotic epoxide hydrolase inhibitor, 3,3,3-trichloropropene 1,2-oxide, potently inhibited microsomal hydrolysis of delta 16-ANDO 16,17-epoxides as well as of benzo[a]pyrene 4,5-epoxide and styrene 7,8-epoxide. Addition of 3,3,3 trichloropropene 1,2-oxide accumulated the 16,17-epoxides formed from delta 16 ANDO in the reaction medium with concomitant decrease in the amounts of the 16,17 glycols formed, leading to a conclusion that the 16,17-epoxides played a role as obligatory intermediates in the microsomal delta 16-oxidation of delta 16-ANDO to the 16,17-glycols. Epoxidation of delta 16-ANDO was stereoselectively mediated by a cytochrome P-450 with quite unique properties to form the 16,17 alpha-epoxide as the major oxidation product and the 16,17 beta-epoxide as the minor. The epoxidation was strongly inhibited with CO, activated with 2-diethylaminoethyl 2,2-diphenylvalerate hydrochloride more than twice as much, and little affected with metyrapone and 7,8-benzoflavone. A pretreatment of the animals with 3 methylcholanthrene induced the delta 16-ANDO-epoxidizing activity of their microsomes 1.5 times higher than those from the control animals. However, a pretreatment with phenobarbital reduced the enzyme activity to one-half of the control microsomes. Under the same conditions, microsomal activities of hydroxylation of benzo[a]pyrene and N-demethylation of benzphetamine were significantly induced by the pretreatments with 3-methylcholanthrene and phenobarbital, respectively. PMID- 4019451 TI - A resonance Raman study of ligand binding geometry in Glycera dibranchiata carbonmonoxyhemoglobin. AB - Using 12CO and 13CO liganded protein and 406 nm laser excitation, multiple stretching (upsilon(Fe-CO), upsilon(C-O)) and bending (delta(Fe-C-O)) modes have been identified in the resonance Raman spectra of monomeric and polymeric Glycera hemoglobins. While the monomer fraction Glycera dibranchiata hemoglobin has upsilon(Fe-CO) = 496 cm-1, two distinct upsilon(Fe-CO) modes are found at 498 cm 1 and 520 cm-1 for the polymeric protein fraction. Data for upsilon(Fe-CO) and upsilon(C-O) were employed in an isolated three-body oscillator calculation to obtain approximate values for the Fe-C-O bond angle of 175 +/- 5 degrees for one polymeric component and 160 +/- 5 degrees for both the monomer and the second identifiable polymeric component. The differences in ligand binding geometry between the Glycera hemoglobins and other hemeproteins can be used to rationalize the relatively high values of on and off rates exhibited by the Glycera hemoglobins. PMID- 4019452 TI - Quantitative estimation of the pathways followed in the conversion to glycogen of glucose administered to the fasted rat. AB - When [6-3H,6-14C]glucose was given in glucose loads to fasted rats, the average 3H/14C ratios in the glycogens deposited in their livers, relative to that in the glucoses administered, were 0.85 and 0.88. When [3-3H,3-14C]lactate was given in trace quantity along with unlabeled glucose loads, the average 3H/14C ratio in the glycogens deposited was 0.08. This indicates that a major fraction of the carbons of the glucose loads was converted to liver glycogen without first being converted to lactate. When [3-3H,6-14C]glucose was given in glucose loads, the 3H/14C ratios in the glycogens deposited averaged 0.44. This indicates that a significant amount of H bound to carbon 3, but not carbon 6, of glucose is removed within liver in the conversion of the carbons of the glucose to glycogen. This can occur in the pentose cycle and by cycling of glucose-6-P via triose phosphates: glucose----glucose-6-P----triose phosphates----glucose-6-P--- glycogen. The contributions of these pathways were estimated by giving glucose loads labeled with [1-14C]glucose, [2-14C]glucose, [5-14C]glucose, and [6 14C]glucose and degrading the glucoses obtained by hydrolyzing the glycogens that deposited. Only a few per cent of the glucose carbons deposited in glycogen were deposited in liver via glucose-6-P conversion to triose phosphates. Between 4 and 9% of the glucose utilized by the liver was utilized in the pentose cycle. While these are relatively small percentages, since three NADP3H molecules are formed from each molecule of [3-3H]glucose-6-P utilized in the cycle, a major portion of the difference between the ratios obtained with [3-3H]glucose and with [6 3H]glucose is attributable to metabolism in the pentose cycle. Because 3H of [3 3H]glucose is extensively removed during the conversion of the glucose to glycogen within liver the extent of incorporation of the 3H into liver glycogen is not the measure of glucose's metabolism in other tissues before its carbons are deposited in liver glycogen. The distributions of 14C from the 14C-labeled glucoses into the carbons of the liver glycogens mean that at a minimum about 30% of the carbons of the glucose deposited in the glycogen were first converted to lactate or its metabolic equivalent. PMID- 4019453 TI - Analysis of ligand binding to receptors by competition kinetics. Application to muscarinic antagonists in rat brain cortex. AB - We propose a method for obtaining kinetic parameters of unlabeled ligands which is based on analyzing the effect of their competition on the binding kinetics of a labeled ligand. In this method (competition kinetics), the binding kinetics of a labeled ligand are measured in the absence and in the presence of given concentrations of a competing unlabeled ligand. The rate equations appropriate to the particular kinetic model may be solved employing linear homogeneous differential equations. The rate constants appearing in the final integrated expressions can be evaluated by nonlinear regression. We have demonstrated the validity and applicability of the method to study receptor systems, using the muscarinic receptors in rat brain cortex as an experimental system. We have determined the various kinetic parameters of two muscarinic antagonists (N-methyl 4-[3H]piperidyl benzilate and (-)-N-[3H]methylscopolamine) by following directly their binding kinetics. These parameters were compared with those obtained for the same unlabeled ligands in homogeneous and heterogeneous competition studies. In all cases, the parameters obtained by the competition kinetics method were close to those extracted from direct binding kinetics, and in cases where both types of studies were performed on the same preparations, the parameters obtained by the two methods were essentially identical. PMID- 4019454 TI - Rate constants of agonist binding to muscarinic receptors in rat brain medulla. Evaluation by competition kinetics. AB - The method of competition kinetics, which measures the binding kinetics of an unlabeled ligand through its effect on the binding kinetics of a labeled ligand, was employed to investigate the kinetics of muscarinic agonist binding to rat brain medulla pons homogenates. The agonists studied were acetylcholine, carbamylcholine, and oxotremorine, with N-methyl-4-[3H]piperidyl benzilate employed as the radiolabeled ligand. Our results suggested that the binding of muscarinic agonists to the high affinity sites is characterized by dissociation rate constants higher by 2 orders of magnitude than those of antagonists, with rather similar association rate constants. In contrast, the major differences between the kinetic binding parameters of agonists and antagonists to the low affinity agonist binding sites are in the association rate constants, which were 2-5 orders of magnitude lower for agonists. This demonstrates that there are basic differences in the interactions of agonists with the low and high affinity sites. Our findings also suggest that isomerization of the muscarinic receptors following ligand binding is significant in the case of antagonists, but not of agonists. Moreover, it is demonstrated that in the medulla pons preparation, agonist-induced interconversion between high and low affinity bindings sites does not occur to an appreciable extent. PMID- 4019455 TI - Cytochrome P-450scc-adrenodoxin interactions. Ionic effects on binding, and regulation of cytochrome reduction by bound steroid substrates. AB - The binding of adrenodoxin to cytochrome P-450scc and the intracomplex electron transfer from the iron-sulfur center to the heme have been studied. Salt sensitivity of the protein complex suggests the participation of electrostatic forces, as is also seen for the complex of adrenodoxin with NADPH-adrenodoxin reductase. Differences in ion specificities for the complexes of adrenodoxin with the other two proteins suggest some differences in binding requirements. Insensitivity of the heme reduction to solution conditions (salt, detergent) and kinetic analysis indicate that the protein complex is formed rapidly and that intracomplex electron transfer then occurs more slowly. Factors governing the rate of this electron transfer were investigated; binding of a series of cholesterol derivatives was used to perturb the spin state, midpoint potential, and reduction rate of the heme, and thus to test for relationships among these parameters. A linear free energy relationship between the substrate-induced midpoint potential and reduction rate is seen, but none of the other parameters (including the strength of substrate binding) are correlated. Data indicate that factors other than spin state (i.e. steric requirements and bonding groups within the steroid-binding site) regulate the strength of steroid binding. The bound steroid then modulates both midpoint potential/reduction rate and spin state but by independent mechanisms. PMID- 4019456 TI - Requirements for the translocation of diphtheria toxin fragment A across lipid membranes. AB - The translocation of the enzymatic moiety of diphtheria toxin, fragment A, across the membranes of pure lipid vesicles was demonstrated. A new assay, which employed vesicles made to contain radiolabeled NAD and elongation factor-2, was used to measure the appearance of the enzymatic activity of the A fragment in the vesicles. When the vesicles were exposed to a low-pH medium in the presence of diphtheria toxin, small molecules, such as NAD, escaped into the extravesicular medium, whereas large molecules mostly remained inside the vesicles. The vesicle entrapped elongation factor-2 became ADP-ribosylated, indicating the entry of fragment A into the vesicle. The translocation of the A fragment depended upon the pH of the medium, being negligible at pH greater than 7.0 and maximal at pH 4.5. The entire toxin molecule was needed for function; neither the A fragment nor the B fragment alone was able to translocate itself across and react with the sequestered substrates. After exposure of the toxin to low pH, the entry of the A fragment was rapid, being virtually complete within 2-3 min at pH 5.5, and within 1 min at pH 4.7. Translocation occurred in the absence of any protein in the vesicle membrane. These results are consistent with the notion that the diphtheria toxin molecule enters the cytoplasm of a cell by escaping from an acidic compartment such as an endocytic vesicle. PMID- 4019457 TI - Sialylation of glycoprotein oligosaccharides with N-acetyl-, N-glycolyl-, and N-O diacetylneuraminic acids. AB - Four common sialic acids (Sia), NeuAc, N-glycolyl-neuraminic acid (NeuGc), 4-O acetyl-N-acetylneuraminic acid (4-O-Ac-NeuAc), and 9-O-Ac-NeuAc were examined for activation to their corresponding CMP-sialic acid conjugates and subsequently for their transfer to glycoprotein oligosaccharides by purified mammalian sialyltransferases. CMP-sialic acid synthetases from calf brain and from bovine and equine submaxillary glands were found to convert NeuAc, NeuGc, and 9-O-Ac NeuAc to their corresponding CMP-sailic acids. In contrast, no conversion of 4-O Ac-NeuAc to CMP-4-O-Ac-NeuAc was observed for any of the three synthetases examined. A new procedure for the preparation of CMP-9-O-Ac-NeuAc, CMP-NeuGc, and CMP-NeuAc in high yield and purity was developed, using the calf brain CMP-sialic acid synthetase. Each of these derivatives was tested as donor substrates for six mammalian sialyltransferases purified from porcine, rat, and bovine tissues, including a bovine GalNAc alpha 2,6 sialyltransferase whose purification is described in this report. The sialyltransferases examined represent those which form the Sia alpha 2,6Gal beta 1,4-GlcNAc-, Sia alpha 2,3Gal beta 1,3(4)GlcNAc-, Sia alpha 2,3Gal beta 1,3-GalNAc- and Sia alpha 2,6GalNAc- sequences found on N linked and O-linked oligosaccharides of glycoproteins. CMP-NeuAc and CMP-NeuGc were equally good donor substrates for all six sialyltransferases. However, transfer of 9-O-Ac-NeuAc from CMP-9-O-Ac-NeuAc varied from only 10% to nearly 70% that of the transfer of NeuAc from CMP-NeuAc. Results are viewed to define the relative roles of direct transfer of these sialic acids and modification of glycosidically bound NeuAc in glycoproteins. PMID- 4019458 TI - Purification and characterization of an O-acetylsialic acid-specific lectin from a marine crab Cancer antennarius. AB - A sialic acid-binding lectin with high specificity for 9-O-acetyl- and 4-O acetylsialic acids was purified from the hemolymph of the California coastal crab, Cancer antennarius, by affinity chromatography using bovine submaxillary mucin coupled to agarose. The binding specificity of the crab lectin distinguishes it from other known sialic acid-specific lectins from Limulus polyphemus and Limax flavus which show a broader range of specificity for sialic acids. The purified lectin is homogenous on sodium dodecyl sulfate-polyacrylamide electropherograms with a subunit molecular weight of about 36 kDa. The specificity of the lectin for O-acetylsialic acids appears to account for the fact that it agglutinates mouse, rat, rabbit, and horse erythrocytes, which contain O-acetylsialic acids on cell surface glycoconjugates, but not human monkey, sheep, goat, and chicken erythrocytes which contain only NeuAc or N glycolylneuraminic acid (NeuGc). This conclusion was supported by the potent inhibition of hemagglutination by bovine and equine submaxillary mucins which contain 9(7,8)-O-acetyl- and 4-O-acetylsialic acids, respectively, and also by free 9-O-acetyl-N-acetylneuraminic acid (9-O-Ac-NeuAc) and 4-O-Ac-NeuAc relative to NeuAc and NeuGc. Further support for the role of O-Ac-sialic acids in hemagglutination of erythrocytes was obtained by enzymatic modification of human erythrocytes. Sialidase-treated erythrocytes were resialylated with purified sialyltransferases and various CMP-sialic acid donor substrates to contain NeuAc or NeuGc or 9-O-Ac-NeuAc in the Sia alpha 2,3Gal or Sia alpha 2,6Gal linkages. Cells resialylated to contain NeuAc or NeuGc were not agglutinated, but cells resialylated to contain 9-O-Ac-NeuAc were agglutinated with high titer, comparable to that of mice or horse erythrocytes. PMID- 4019459 TI - Molecular cloning and nucleotide sequence of the cDNA for rat peroxisomal enoyl CoA: hydratase-3-hydroxyacyl-CoA dehydrogenase bifunctional enzyme. AB - For the studies on the mechanism of induction of peroxisomal beta-oxidation enzymes and biogenesis of the organelle, we have isolated cDNA clones for rat peroxisomal enoyl-CoA: hydratase-3-hydroxyacyl-CoA dehydrogenase bifunctional enzyme. On blotting experiments with liver RNA, the cDNAs hybridized to a 3.0 kilobase RNA which was increased 5-7-fold by the administration of di-(2 ethylhexyl)phthalate to rats. Nucleotide sequencing was carried out for four cloned cDNAs and one obtained by a primer extension method. By overlapping these sequences with each other, we identified 20 nucleotides of 5'-noncoding, 2,166 nucleotides of coding, and 910 nucleotides of 3'-noncoding regions. The deduced amino acid sequence of the enzyme is composed of 722 residues, and the composition agrees with that of the protein data. The sequence was confirmed by the amino acid compositions and sequence analyses of some of the tryptic peptides. The molecular weight of the mature enzyme is calculated to be 78,511 from the predicted amino acid sequence. The enzyme has no terminal peptide extension as a signal for translocation into peroxisomes. PMID- 4019460 TI - Transient methylation of dolichyl oligosaccharides is an obligatory step in halobacterial sulfated glycoprotein biosynthesis. AB - Biosynthesis of sulfated saccharides that are linked to asparagine residues in the cell surface glycoprotein of Halobacterium halobium via a glucose residue involves sulfated dolichyl-monophosphoryl oligosaccharide intermediates (Lechner, J., Wieland, F., and Sumper, M. (1985) J. Biol. Chem. 260, 860-866). During isolation and characterization of these lipid oligosaccharides we detected a group of related compounds containing additional unidentified sugar residues. Here we report that: 1) the unknown sugar residues were 3-O-methylglucose, linked peripherally to the lipid-saccharide intermediates; 2) the 3-O-methylglucose residues in the oligosaccharides occur only at the lipid-linked level but are absent at the protein-linked level; 3) cell surface glycoprotein biosynthesis in Halobacteria in vivo is drastically depressed when S-adenosylmethionine-dependent methylation is inhibited, indicating that methylation is an obligatory step during glycoprotein synthesis. We propose a mechanism for the transport of lipid oligosaccharides through the cell membrane, involving an intermediate stage in which the saccharide moieties are transiently modified with 3-O-methylglucose. PMID- 4019461 TI - Distinct forebrain and cerebellar isozymes of type II Ca2+/calmodulin-dependent protein kinase associate differently with the postsynaptic density fraction. AB - Forebrain and cerebellar Type II Ca2+/calmodulin-dependent protein kinases have different subunit compositions. The forebrain holoenzyme, characterized in our laboratory, is a 650-kDa holoenzyme composed of 50-kDa alpha-subunits and 60-kDa beta-subunits assembled in approximately a 3:1 ratio (Bennett, M. K., Erondu, N. E., and Kennedy, M. B. (1983) J. Biol. Chem. 258, 12735-12744). The cerebellar isozyme is a 500-kDa holoenzyme composed of alpha-subunits and beta-subunits assembled in almost the converse ratio, approximately four beta-subunits for each alpha-subunit. When compared by tryptic peptide mapping and by immunochemical techniques, the beta-subunits from the two brain regions are indistinguishable and the alpha-subunits appear closely related. The specific activities, substrate specificities, and catalytic constants of the cerebellar and forebrain isozymes are similar, suggesting that the alpha- and beta-subunits contain similar catalytic sites. However, two differences in the properties of the isozymes may result in functional differences between them in vivo. First, the apparent affinity of the cerebellar kinase for Ca2+/calmodulin is 2-fold higher than that of the forebrain kinase. Second, the two isozymes appear to associate differently with subcellular structures. Approximately 85% of the cerebellar kinase and 50% of the forebrain kinase remain in the particulate fraction after homogenization under standard conditions. However, they are present in different amounts in postsynaptic density fractions. Postsynaptic densities prepared from forebrain contain the forebrain isozyme. Immunochemical measurements show that it comprises approximately 16% of their total protein. In contrast, postsynaptic densities prepared from cerebellum contain the cerebellar isozyme, but it comprises only approximately 1-2% of their total protein. Thus, the alpha-subunit may play a role in anchoring Type II Ca2+/calmodulin-dependent protein kinase to postsynaptic densities. PMID- 4019462 TI - Purification and characterization of the human liver cytochromes P-450 involved in debrisoquine 4-hydroxylation and phenacetin O-deethylation, two prototypes for genetic polymorphism in oxidative drug metabolism. AB - Two forms of cytochrome P-450 were purified to apparent homogeneity from several different preparations of human liver microsomes. One form, designated P-450DB, had relatively high catalytic activity towards the drugs debrisoquine, sparteine, bufuralol (both the (+)- and (-)-isomers), encainide, and propranolol and appears to be the enzyme involved in the polymorphic distribution of oxidative activities towards these substrates in humans. The other form, designated P-450PA, had relatively high phenacetin O-deethylase activity and appears to be involved in the variation of this activity among humans. Polyclonal antibodies raised to the two enzymes were specific for the antigens as judged by immunoelectrophoresis and immuno-inhibition studies. The two enzymes and their activities were distinguished by chromatographic separation, sodium dodecyl sulfate polyacrylamide gel electrophoresis, amino acid composition, immuno-inhibition studies, and steady-state kinetic assays. Immunochemical studies suggest that each form represents only a small fraction of the total cytochrome P-450 in human liver microsomes. These biochemical studies provide a basis for better understanding the mechanisms which underlie genetic polymorphisms involving P-450 cytochromes in humans. PMID- 4019463 TI - Shortening velocity in single fibers from adult rabbit soleus muscles is correlated with myosin heavy chain composition. AB - Extensive variations exist in the heavy and light chain components of myosin in vertebrate striated muscles. In the present study, we have characterized a specific contractile property, velocity of shortening, and protein subunit composition of single fibers from adult rabbit soleus muscles. Maximum velocity of shortening (Vmax) was measured using the slack test method, and the myosin composition of these same fibers was determined using an ultrasensitive sodium dodecyl sulfate-polyacrylamide gel electrophoresis system. While most fibers were found to have velocities between 0.5 and 1.0 muscle length/s, several had velocities distributed between 1.33 and 2.99 muscle length/s. The fibers in the slower group had myosin subunits that were solely of the slow type; however, those in the faster group contained both fast and slow heavy chains and light chains. The velocity of shortening measured in fibers having both myosin types was highly correlated with the myosin heavy chain composition, with velocity increasing as the proportion of fast-type heavy chain increased. Variations in light chain composition, particularly fast and slow myosin light chain 1, appeared to occur independently of the variations in heavy chain composition, suggesting that some myosin molecules consist of mixtures of slow- and fast-type subunits. PMID- 4019464 TI - A multilocus system for studying tissue and subcellular specialization. The three NADP-dependent isocitrate dehydrogenase isozymes of the fish Fundulus heteroclitus. AB - Three NADP-dependent isocitrate dehydrogenase isozymes in the teleost, Fundulus heteroclitus (L.), exhibit differences in tissue and subcellular distribution. These three proteins were purified and characterized as to native and subunit molecular weight, isoelectric pH, susceptibility to thermal denaturation, and certain kinetic parameters (Km and Vmax) for the oxidative decarboxylation of isocitrate at 25 degrees C and pH 7.4. The enzymes are dimers of 90 +/- 4 kDa with subunit molecular masses of 45 +/- 3 kDa. Isoelectric pH values were 7.00, 5.19, and 5.29 for IDH-A2, IDH-B2 and IDH-C2 (where IDH represents isocitrate dehydrogenase), respectively. While the monomer-dimer equilibrium is not influenced by substrates, the equilibrium appears to respond to buffer concentration and temperature. Enzyme activity is not affected upon dilution in the presence of buffer containing bovine serum albumin, however, its activity declines rapidly in the absence of bovine serum albumin. Thermal stability varies among the isozymes, and they do not denature by a simple first-order process. The presence of substrates, metal, and coenzymes independently provided enzyme stability, suggesting a random mechanism of substrate and cofactor binding. While IDH-A2 and IDH-B2 have identical KISOCm, IDH-B2 has a lower KNADPm. The most common mitochondrial isozyme (IDH-C2) has a greater KISOCm than either the less common mitochondrial isozyme (IDH-A2) or the cytoplasmic enzyme (IDH-B2). The KNADPm for IDH-C2 was the same as that of IDH-A2 but greater than that of IDH-B2. These Km differences are consistent with the cytoplasmic-mitochondrial shuttling of NADPH-reducing equivalents into the cytoplasm. PMID- 4019465 TI - Lateral mobility and organization of phospholipids and proteins in rat myocyte membranes. Effects of aging and manipulation of lipid composition. AB - The effects of aging and of liposome treatment on the lateral mobility of phospholipids and proteins in the plasma membrane of cultured rat heart myocytes were studied by fluorescence photobleaching recovery. Both the mobile fraction (R) and the lateral diffusion coefficient (D) of the fluorescent phospholipid N-4 nitrobenzo-2-oxa-1,3-diazolyl phosphatidylethanolamine were found to depend on the culture's age. Aged myocyte cultures (15 days old) demonstrated higher R and lower D as compared with young ones (5 days old). Treatment of aged cultures with phosphatidylcholine (PC) liposomes, which increases the PC/sphingomyelin (SM) ratio and decreases the cholesterol level, reversed the D value to the level observed in young cultures and decreased R below the value encountered in young cells. Treatments with SM liposomes (which induce cholesterol depletion without altering the PC/SM ratio) and with PC/cholesterol (1:0.9) liposomes (which increase the PC/SM ratio without cholesterol depletion) have indicated that the PC-liposome effect is due to changes in both the PC/SM ratio and in the cholesterol level. Analogous experiments on the mobility of succinyl-concanavalin A receptors yielded similar effects on R, without altering the D value. The changes in the D and R values of the markers studied are most likely initiated by the observed alterations in the myocyte lipid composition under the conditions employed. The possible involvement of changes in the organization of membrane lipids in domains in the observed phenomena is discussed. PMID- 4019466 TI - A sulfatase specific for glucuronic acid 2-sulfate residues in glycosaminoglycans. AB - Although 2-O-sulfated L-iduronic acid (IdoA) residues have been known to occur in heparin, 2-O-sulfated D-glucuronic acid (GlcA) residues have been reported only recently (Bienkowski, M. J., and Conrad, H. E. (1985) J. Biol. Chem. 250, 356 365). Disaccharides prepared by cleavage of heparin and N-deacetylated chondroitin 6-sulfate with nitrous acid were used to demonstrate a new sulfatase that catalyzed the removal of the 2-O-sulfate substituents from GlcA but not IdoA residues. The deamination products were labeled by NaB3H4 reduction to give disaccharides from heparin and chondroitin sulfate which had reducing terminal 2,5-anhydro-D-mannitol ([3H]AManR) and 2,5-anhydro-D-talitol ([3H]ATalR) residues, respectively. IdoA(2-SO4)-[3H]AManR(6-SO4) from heparin and GlcA(2-SO4) [3H]ATalR(6-SO4) from chondroitin sulfate were purified for use as substrates. GlcA(2-SO4)-[3H]AManR(6-SO4) was prepared by epimerization of IdoA(2-SO4) [3H]AManR(6-SO4) with hydrazine at 100 degrees C. Lysosomal enzyme preparations from chick embryo chondrocytes and from two normal human fibroblast cell lines catalyzed the removal of the 2-O-SO4 substituent from the uronic acid residues of IdoA(2-SO4)-[3H]AManR(6-SO4), GlcA(2-SO4)-[3H] AManR(6-SO4), and GlcA(2-SO4) [3H]ATalR(6-SO4). In contrast, a lysosomal enzyme preparation from a human fibroblast cell line deficient in idurono-2-sulfatase (Hunter's-syndrome), which had no activity on the IdoA(2-SO4)-[3H]AManR(6-SO4), converted GlcA(2-SO4) [3H]AManR(6-SO4) to a mixture of GlcA-[3H] AManR(6-SO4) and [3H]AManR(6-SO4). This enzyme also converted GlcA(2-SO4)-[3H]ATalR(6-SO4) to a mixture of GlcA [3H]ATalR(6-SO4) and [3H]ATalR(6-SO4). Digestion of both GlcA(2-SO4)-[3H]AManR(6 SO4) and GlcA(2-SO4)-[3H]ATalR(6-SO4) was inhibited by 35SO2-4 and was arrested at the monosulfated disaccharide stage by 1,4-saccharolactone. The glucurono-2 sulfatase exhibited a pH optimum of 4. The results indicate that there exists a separate sulfatase for the removal of sulfate substituents from C-2 of GlcA residues in glycosaminoglycans. PMID- 4019467 TI - Formation of a leakage-type ion pathway in lipid bilayer membranes by divalent cationic cyanine dyes in cooperation with inorganic phosphate. Role of the cyanine dye in uncoupling of oxidative phosphorylation. AB - Divalent cationic cyanine dyes, such as 2,2'-[3-[2-(3-butyl-4-methyl-2-thiazoline 2-ylidene)-ethylidene] propenylene]bis[3-butyl-4-methylthiazolinium iodide] and platonin induced large membrane current fluctuation when an electrical potential difference was applied across a planar phosphatidylserine bilayer membrane in medium containing inorganic phosphate (Pi). Without Pi, the dyes did not induce current fluctuation at concentrations of less than 30 microM. Noise analysis of current fluctuation indicated formation of a pathway for ion leakage. From measurements of the interfacial tension between oil and aqueous phases, and of water permeability across liposomal membranes, Pi was concluded to relax the phospholipid bilayer structure, resulting in great reduction in the concentration of the cyanine dye necessary for induction of the leakage-type pathway. In the presence of Pi, cationic ions such as tetrabutyl ammonium and tetraphenyl phosphonium did not induce the leakage-type pathway, although they had electrophoretic effects at high concentrations. These facts suggest that the mechanism of the uncoupling of oxidative phosphorylation by dicationic cyanine dyes in mitochondria is different from that of cationic uncouplers such as tetrabutyl ammonium ion. PMID- 4019468 TI - O2-triggered changes of membrane fatty acid composition have no effect on Arrhenius discontinuities of respiration in sycamore (Acer pseudoplatanus L.) cells. AB - Sycamore cells (Acer pseudoplatanus L.) in suspension culture were grown at 25 degrees C in culture medium containing two oxygen concentrations: 250 microM O2 (standard conditions) and 10 microM O2 (O2-limiting conditions). The decrease of O2 concentration in the culture medium did not modify significantly the relative proportion of each phospholipid. In contrast, the molar proportion of fatty acids was dramatically changed in all lipid classes of the cell membranes; the average percentage of oleate increased from 3 to 45% whereas that of linoleate decreased from 49 to 22%. When normal culture conditions were restored (250 microM O2), oleate underwent a rapid desaturation process; the loss of oleic acid was associated with a stoichiometric appearance of linoleic acid at a rate of about 4 nmol of oleate desaturated/h/10(6) cells. Under these conditions, no change in the Arrhenius-type plots of the rate of sycamore cell respiration was observed; the values of the transition temperature and of the Arrhenius activation energy (Ea) associated with the cell respiration as well as with the respiration associated enzymes remained unchanged. Thus it was concluded that the fact that a strong decrease in the fraction of unsaturated fatty acid residues present in the mitochondria had no effect on electron transport rates and Arrhenius plot discontinuities casts doubt on the significance of such changes in terms of chilling injury. Finally it is suggested that some of the Arrhenius discontinuities observed at the level of membrane enzyme could be the consequence of intrinsic thermotropic changes in protein arrangement independent of lipid fluidity. PMID- 4019469 TI - Azidocytidine is a specific inhibitor of deoxyribonucleotide synthesis in 3T6 cells. AB - 2'-Azidocytidine is a specific inhibitor of DNA synthesis in cultured 3T6 mouse fibroblasts. Earlier work (Akerblom, L., Pontis, E., and Reichard, P. (1982) 257, 6776-6782) indicated that the nucleoside, after phosphorylation, acted by inhibiting both ribonucleotide reduction and DNA strand elongation. We now demonstrate that the effect on strand elongation was due to a contamination of azidocytidine with less than 0.3% of arabinosyl cytosine. Pure azidocytidine inhibits specifically ribonucleotide reductase and its effects on DNA synthesis are secondary to this inhibition. The results with azidocytidine concerning the size and turnover of deoxyribonucleoside triphosphate pools parallel those of hydroxyurea and are distinct from those of arabinosyl cytosine. Together with hydroxyurea, azidocytidine is a useful compound in studies aiming at a specific block of the production of deoxynucleoside triphosphates in intact cells. Comparisons of the effects of azidocytidine and arabinosyl cytosine complement earlier studies with hydroxyurea and aphidicolin concerning inter-relations between dNTP synthesis and DNA replication. PMID- 4019470 TI - Methanogenesis and the K+ transport system are activated by divalent cations in ammonia-treated cells of Methanospirillum hungatei. AB - We describe a K+ transport system in Methanospirillum hungatei cells depleted of cytoplasmic K+ via an ammonia/K+ exchange reaction (Sprott, G. D., Shaw, K. M., and Jarrell, K. F. (1984) J. Biol. Chem. 259, 12602-12608). Ammonia-treated cells contained low concentrations of ATP and were unable to make CH4 or to transport 86Rb+. All of these properties were restored by CaCl2, MgCl2, or MnCl2, and not by CoCl2 or NiCl2. The Rb+ transport system had a Km of 0.42 and Vmax of 29 nmol/min X mg; K+ inhibited competitively. Both H2 and CO2 were required for appreciable transport, whereas air, valinomycin, or nigericin were potent inhibitors. The influx of Rb+ was electrogenic and associated with proton efflux, producing a delta pH (alkaline inside) in acidic media. In the absence of K+ (or Rb+), the activation of CH4 synthesis by Mg2+ produced little change in the cytoplasmic pH, showing that methanogenesis did not elicit a net efflux of protons. The pH optimum for transport was in the range 6.0-7.3 where the transmembrane pH gradient would contribute minimally to the proton motive force. Protonophores at pH 6.3 caused a partial decline in CH4 synthesis and the ATP content and dramatically collapsed Rb+ transport. These and other inhibitor experiments, coupled with the fact that the Rb+ gradient was too large to be in equilibrium with the proton motive force alone, suggest a role for both ATP and the proton motive force in Rb+ transport. Also, a role for K+ in osmoregulation is indicated. PMID- 4019471 TI - The regulation of heme biosynthesis during erythropoietin-induced erythroid differentiation. AB - Marrow cells induced toward erythroid differentiation by treatment with erythropoietin respond by increasing the rates of iron uptake and hemoglobin synthesis. Study of the enzymes of heme biosynthesis during erythroid differentiation suggests that induction of heme synthesis in these cells is regulated by synthesis of porphobilinogen deaminase. The activities of delta aminolevulinic acid synthase, gamma, delta-dioxovaleric acid transaminase, delta aminolevulinic acid dehydratase, and ferrochelatase were not affected significantly by treatment of suppressed marrow cells with erythropoietin over a period of 4 days, whereas that of porphobilinogen deaminase was increased by as much as 3.5-fold by the 3rd day of incubation. The time course of increase in porphobilinogen deaminase activity was parallel to that of the increase in heme synthesis. Moreover, when porphobilinogen deaminase activity was compared in marrow cells exposed to increased levels of erythropoietin in vivo (hyperplastic marrow) and marrow cells exposed to lowered levels of erythropoietin in vivo (suppressed marrow), the activity in the former case was greater than that in normal cells and for the latter type of cell it was lower than normal. Experiments using actinomycin D and cycloheximide suggest that transcription is required for the erythropoietin-induced porphobilinogen deaminase activity, indicating that induction is probably at the level of de novo synthesis of enzyme. PMID- 4019472 TI - Metal and phospholipid binding properties of partially carboxylated human prothrombin variants. AB - To study the specific role of gamma-carboxyglutamic acid (Gla) residues in prothrombin, we have isolated a series of partially carboxylated prothrombin variants from a patient with a hereditary defect in vitamin K-dependent carboxylation (Goldsmith, G. H., Pence, R. E., Ratnoff, O. D., Adelstein, D. A., and Furie, B. (1982) J. Clin. Invest. 69, 1253-1260). The three variant prothrombins, purified by DEAE-Sephacel, immunoaffinity chromatography, and preparative gel electrophoresis, were indistinguishable from prothrombin in molecular weight, amino acid composition, and NH2-terminal amino acid sequence, with the exception of Gla residues. Variant prothrombin 1, with 8 Gla residues, had 66% of the coagulant activity of prothrombin, one high affinity metal-binding site (Kd = 15 nM), and three lower affinity sites (Kd = 2.7 microM); prothrombin contained two high affinity (36 nM) and four lower affinity sites (Kd = 1 microM). Ca(II) induced a 23% decrease in the intrinsic fluorescence of variant prothrombin 1 fragment 1, compared to a 35% decrease in that of prothrombin fragment 1. The phospholipid binding activity of variant prothrombin 1 was 44% that of prothrombin. Variant prothrombin 2 and variant prothrombin 3, with 4 and 6 Gla residues, respectively, had about 5% of prothrombin coagulant activity and a single high affinity and two lower affinity metal-binding sites and exhibited no phospholipid binding activity. Variant prothrombin 3 fragment 1 and variant prothrombin 2 fragment 1 demonstrated 18 and 13% of Ca(II)-induced fluorescence quenching, respectively. Abnormal prothrombin, with 1 Gla residue, had 8% of prothrombin coagulant activity, a single lower affinity (1 microM) metal-binding site, and 13% Ca(II)-induced fluorescence quenching of the fragment 1 species and did not bind to phospholipid. These results indicate that Gla residues define the metal binding properties of prothrombin. Most, if not all, of the Gla residues are required for complete prothrombin function, and the prothrombin coagulant activity correlates to the phospholipid binding activity of the prothrombin species. PMID- 4019473 TI - Epoxidation of styrene by hemoglobin and myoglobin. Transfer of oxidizing equivalents to the protein surface. AB - Methemoglobin and metmyoglobin catalyze the H2O2-dependent oxidation of styrene to styrene oxide and benzaldehyde. The formation of styrene oxide requires molecular oxygen as well as H2O2 but does not, as shown by inhibitor studies, involve the superoxide or hydroxyl radicals. Approximately 38, 67, and 78% of the oxygen in styrene oxide derives from 18O2 in the reactions catalyzed, respectively, by bovine hemoglobin, sperm whale myoglobin, and equine heart myoglobin, whereas 70, 55, and 35% of the oxygen can be shown to be derived from [18O]H2O2. However, a larger fraction of the epoxide oxygen than suggested by the labeling data (perhaps all) derives from molecular oxygen rather than H2O2 because the hemoproteins produce molecular oxygen from the peroxide. The epoxidation of styrene by methemoglobin gives equal amounts of the R and S enantiomers and, as shown by studies with trans-[1-2H]styrene, proceeds with partial (33%) loss of the olefin stereochemistry. The results are rationalized by H2O2-dependent formation of a protein radical that combines with molecular oxygen to give a protein-peroxy radical that oxidizes styrene. PMID- 4019474 TI - Metabolic studies of pyruvate- and lactate-perfused guinea pig hearts by 13C NMR. Determination of substrate preference by glutamate isotopomer distribution. AB - Guinea pig hearts perfused in vitro with 99% enriched [3-13C]pyruvate and [3 13C]lactate have been examined by 13C NMR spectroscopy at 75.45 MHz. Resonances from the intracellular metabolites, glutamate, aspartate, alanine, citrate, malate, lactate, and acetylcarnitine are detected in the [3-13C]pyruvate-perfused hearts while glutamate is the only metabolite observed in the [3-13C]lactate perfused hearts. Extracts obtained from individual freeze-clamped hearts run under high resolution conditions show similar distributions of metabolites indicating that the intracellular concentrations of these metabolites are indeed quite dependent upon the substrate being utilized. The excellent signal to noise in the spectra of lactate-perfused hearts allows observation of spin-spin coupling between 13C-enriched nuclei in the various glutamate isotopomers within the intact heart. It is shown that the steady-state distribution of glutamate isotopomers is determined by the amount of 12C- versus 13C-enriched acetyl-CoA entering the citric acid cycle and this provides the basis for a direct determination of substrate utilization by the heart in the presence of competing substrates. Similar information may be derived from the 13C spectrum of an extract prepared from a single [3-13C]pyruvate-perfused heart. Our results indicate that lactate is preferred over glucose by the guinea pig heart even in the presence of insulin. PMID- 4019475 TI - Characterization of proteoglycans from adult bovine tendon. AB - Proteoglycans were extracted in good yield from the proximal, fibrous portion of adult bovine tendon with 4 m guanidine HCl. They comprise less than 1% of the dry weight of the tissue. Using CsCl density gradient centrifugation, gel chromatography, and ion exchange chromatography, two populations of proteoglycans were separated and purified from other tissue proteins. One was a large, chondroitin sulfate proteoglycan with high buoyant density in CsCl. This component appeared to be composed of two or three subpopulations as detected by agarose/polyacrylamide electrophoresis, although they could not be effectively separated from one another for individual characterization. As a group, the large proteoglycans eluted from Sepharose CL-2B with Kav from 0.1-0.5 and their core protein had Mr greater than 200,000 with high contents of glutamic acid, serine, and glycine. The glycosaminoglycan chains had a weight average Mr of 17,000 and more than 98% of the uronic acid was glucuronic acid. This group comprised only 12% of the total proteoglycan of the tissue. The other 88% of the proteoglycans appeared to represent one group of small molecules that eluted from Sepharose CL 2B at Kav = 0.70. They demonstrated buoyant densities in a CsCl gradient ranging from greater than or equal to 1.51 to 1.30 g/ml. Their core protein had an apparent Mr = 48,000 following removal of the glycosaminoglycan chains by digestion with chondroitinase ABC. This core protein had a particularly high content of aspartic acid/asparagine and leucine. The glycosaminoglycan chains had a weight average Mr of 37,000 and were dermatan sulfate containing 73% iduronic acid. Those molecules found at highest buoyant density appeared to have additional glycosaminoglycan chains that were shorter. Proteoglycans were also extracted from the pressure-bearing distal region of this tendon, where contents of proteoglycan per wet weight of tissue were 3-fold higher and as much as 50% of this was as large as the large proteoglycans from the proximal tissue. Preparations of large proteoglycans from both tendon regions contained molecules capable of interacting with hyaluronic acid. PMID- 4019476 TI - Dissociation of nucleosomal particles by chemical modification. Equivalence of the two binding sites for H2A.H2B dimers. AB - Treatment of nucleosomal particles with dimethylmaleic anhydride, a reagent for protein amino groups, is accompanied by a biphasic release of histones H2A plus H2B; one H2A.H2B dimer is more easily released than the other. This behavior allows the preparation of nucleosomal particles containing only one H2A.H2B dimer, which were complemented with 125I-labeled H2A.H2B. These reconstituted particles, which contain one labeled and one unlabeled H2A.H2B dimer, were treated with the amount of reagent needed to release one of the two H2A.H2B dimers. Radioactivity was equally distributed between residual particles and released proteins, which is consistent with equivalent binding sites in the nucleosomal particle for H2A.H2B dimers, rather than with intrinsically different sites. The asymmetric release of H2A.H2B dimers would be caused by a change in the binding site of one dimer following the release of the other. This behavior might be related to the structural dynamics of nucleosomes. PMID- 4019477 TI - Crystals of crotoxin suitable for high resolution x-ray diffraction analysis. AB - The phospholipasic presynaptic neurotoxin, crotoxin, has been crystallized in a morphology suitable for single crystal x-ray diffraction analysis. The conditions for growth and the unit cell parameters (P4(1)22 or P4(3)22, a = b = 38.5 A, c = 256.9 A, 1 molecule/asymmetric unit) are similar to the very thin plate-like crystals which have been studied with electron diffraction and electron microscopy by Chiu and his colleagues (Jeng, T.-W., Chiu, W., Zemlin, F., and Zeitler, E. (1984) J. Mol. Biol. 175, 93 - 97). These two macroscopic crystal morphologies of what is likely to be a very similar, if not identical, lattice structure will permit the complementary application of electron diffraction/microscopy and x-ray diffraction to understanding the structural basis of the interactions between a phospholipasic neurotoxin and its membrane target. PMID- 4019478 TI - Biosynthesis of the cancer-associated sialyl-Lea antigen. AB - A cancer-associated glycolipid antigen defined by monoclonal antibody 19-9 has the structure NeuAc alpha 2-3Gal Gal beta 1-3GlcNAc beta 1-3Gal beta 1-4Glc beta 1-Cer. We have (formula; see text) studied its biosynthesis by testing the capacity of a crude microsomal fraction of SW 1116 cells to catalyze the addition of fucosyl or sialyl residues from GDP-fucose or CMP-sialic acid to glycolipid or oligosaccharide precursors. When the tetrasaccharide NeuAc alpha 2-3Gal beta 1 3GlcNAc beta 1-3Gal beta 1-4Glc (LSTa) is incubated with GDP-[14C]fucose and SW 1116 microsomes, a 14C-labeled oligosaccharide is formed that can be separated from the incubation mixture on an affinity column containing antibody 19-9 bound to protein A-Sepharose. The product migrates slower than LSTa when analyzed by paper or thin-layer chromatography. After treatment with neuraminidase, it co migrates with the pentasaccharide Gal beta 1-3GlcNAc beta 1-3Gal beta 1-4Glc (formula; see text) (LNF II) in both chromatographic systems. Similar experiments demonstrate that SW 1116 microsomes catalyze the addition of a sialyl residue to the tetrasaccharide Gal beta 1-3GlcNAc beta 1-3Gal beta 1-4Glc to form LSTa. However, when LNF II is incubated with CMP-[14C]sialic acid and SW 1116 microsomes, no 19-9-active product is detected by affinity chromatography or by paper or thin-layer chromatography. Results using glycolipid precursors are consistent with these findings and also demonstrate the presence of the Lewis fucosyltransferase in SW 1116 cells. Thus, the biosynthesis of the sialyl-Lea antigen proceeds by addition of sialic acid to a type 1 precursor chain by a sialyltransferase, followed by addition of fucose by the Lewis fucosyltransferase. PMID- 4019479 TI - Mevalonate utilization in Pseudomonas sp. M. Purification and characterization of an inducible 3-hydroxy-3-methylglutaryl coenzyme A reductase. AB - Pseudomonas sp. M grown on mevalonate as the sole source of carbon has 200- to 800-fold induced levels of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase. The enzyme, which was purified to a homogeneous state in 54% yield (final specific activity, 60.5 mumol of NAD+ reduced per min per mg of protein), converted R-mevalonate (Km = 0.15 mM) to S-HMG-CoA. Activity was sensitive to sulfhydryl modifying reagents. The apparent molecular weight of the holoenzyme was 178,000 and that of the subunit 43,000. The enzyme thus appears to be a tetramer. Comparison of a 23-residue amino-terminal sequence with the cDNA derived sequence of Chinese hamster ovary cell HMG-CoA reductase showed little homology and antibody raised against the Pseudomonas enzyme did not appear to cross-react with rat liver HMG-CoA reductase. Addition of mevalonate to cells growing on glucose was followed by a rapid and biphasic induction of HMG-CoA reductase activity. During phase I, mevalonate or its catabolites may accumulate in intact cells of Pseudomonas sp. M and acetoacetate, a competitive inhibitor of HMG-CoA reductase (Ki = 3.2 mM), may feedback inhibit the enzyme under these conditions. PMID- 4019480 TI - Identification of a 43-kDa polypeptide associated with acetylcholine receptor enriched membranes as MM creatine kinase. AB - Creatine kinase isoenzymes from Torpedo californica electric organ, skeletal muscle, and brain were purified and characterized. Torpedo electric organ and skeletal muscle creatine kinase have identical apparent Mr, electrophoretic mobility, and cyanogen bromide fragments. The electrophoretic mobility of the Torpedo creatine kinase was anodal as compared to mammalian MM creatine kinase. No creatine kinase isoenzyme with an electrophoretic mobility similar to mammalian BB creatine kinase was seen in any of the Torpedo tissues examined. Hybridization studies demonstrate the Torpedo electric organ creatine kinase to be composed of identical subunits and capable of producing an enzymatically active heterodimer when combined with canine BB creatine kinase. Creatine kinase from sucrose gradient-purified Torpedo electric organ acetylcholine receptor-rich membranes has an electrophoretic mobility identical with the cytoplasmic isoenzyme and an apparent Mr identical with mammalian MM creatine kinase. Western blot analysis showed Torpedo electric organ skeletal muscle creatine kinase and acetylcholine receptor-enriched membrane creatine kinase reacted with antiserum specific for canine MM creatine kinase. NH2-terminal amino acid sequence determinations show considerable sequence homology between human MM, Torpedo electric organ, chicken MM, and porcine MM creatine kinase. The acetylcholine receptor-associated creatine kinase is, therefore, identical with the cytoplasmic form from the electric organ and is composed of M-subunits. PMID- 4019481 TI - Mechanism of microtubule assembly. Changes in polymer structure and organization during assembly of sea urchin egg tubulin. AB - Assembly of tubulin, purified from eggs of the sea urchin Stronglyocentrotus purpuratus, was examined at physiological (18 degrees C) and nonphysiological (37 degrees C) temperatures. Critical concentrations for assembly were 0.71 mg/ml at 18 degrees C and 0.21 mg/ml at 37 degrees C. At tubulin concentrations above 1.2 mg/ml at 18 degrees C and 0.5 mg/ml at 37 degrees C, a concentration-dependent "overshoot" in turbidity and in small-angle light scattering was observed; turbidity and scattering increased rapidly to a peak, then decreased asymptotically toward a steady-state value. Quantitative sedimentation analysis revealed that the mass of assembled polymer reached and maintained a constant level during overshoot of turbidity. Changes in the wavelength dependence of turbidity were consistent with the initial formation of sheets of tubulin, followed by conversion of the sheets to microtubules, both at 18 and 37 degrees C. Examination by negative-stain electron microscopy showed that sheetlike structures predominated during the early stages of overshoot assembly, while complete microtubules were present at steady state. Furthermore, measurements of average polymer length revealed that the overshoots in turbidity and in light scattering are unlikely to be caused by polymer length redistribution. Qualitative observations of solution birefringence suggested that the polymer became progressively more aligned during assembly. These results suggest that the turbidity/light-scattering overshoots reflect changes in the form or in the organization of the assembling polymer, or both. PMID- 4019482 TI - Independent regulation of ppp(A2'p)nA-dependent RNase in NIH 3T3, clone 1 cells by growth arrest and interferon treatment. AB - The regulation of ppp(A2'p)nA-(2-5A)-dependent RNase (RNase L or RNase F) was investigated in NIH 3T3, clone 1 cells using 2-5A-binding and nuclease activity assays. Minimal levels of 2-5A-dependent RNase were detected in actively dividing clone 1 cells; these levels were independently induced by growth arrest or interferon treatment. Accordingly, levels of the RNase were enhanced during growth arrest by confluency regardless of the presence or absence of interferon or antibody to interferon in the media. Measurement of 2-5A-dependent RNase was unaffected by the addition of any of six different proteinase inhibitors to the cells prior to extraction. The expression of 2-5A-dependent RNase in growth arrested, interferon-treated cells was still relatively low (about one-third to one-half of that found in similarly treated murine Ehrlich ascites tumor cells). Although this amount of 2-5A-dependent RNase could not be detected by 2-5A mediated ribosomal RNA cleavage, the activity was identified using a more sensitive novel assay for 2-5A-dependent RNase. In addition, introduction of 2-5A or poly(I) X poly(C) into growth-arrested, interferon-treated cells resulted in some inhibition of protein synthesis. The results indicated that the expression of 2-5A-dependent RNase in NIH 3T3, clone 1 cells is regulated under different physiological conditions and that low levels of 2-5A-dependent RNase were insufficient to significantly inhibit encephalomyocarditis virus replication. PMID- 4019483 TI - Demonstration of a COOH-terminal extension on equine lutropin by means of a common acid-labile bond in equine lutropin and equine chorionic gonadotropin. AB - The beta subunits of equine lutropin and equine chorionic gonadotropin were incubated in 0.013 N HCl for 30 min at 110 degrees C and separated into two fragments by reverse-phase high performance liquid chromatography. The amino acid and carbohydrate compositions of both fragments from each subunit were analyzed. The results demonstrated that equine lutropin-beta has a glycosylated COOH terminal extension that differs only in carbohydrate composition from the COOH terminal portion of equine chorionic gonadotropin-beta. This is the first demonstration of a glycosylated COOH-terminal extension in a pituitary glycoprotein hormone. PMID- 4019484 TI - Evidence that anion transport by band 3 proceeds via a ping-pong mechanism involving a single transport site. A 35 Cl NMR study. AB - Band 3 catalyzes the one-for-one exchange of monovalent anions across the red cell membrane. At least two anion binding sites have been postulated to exist on the transport unit: 1) a transport site that has been observed by saturation kinetics and by 35 Cl NMR studies of chloride binding, and 2) a 35Cl NMR invisible inhibitory site that has been proposed to explain the inhibition of anion exchange at large anion concentrations. A number of independent studies have indicated that the transport site is alternately exposed to different sides of the membrane during the transport cycle. Yet the role, if any, of the postulated inhibitory site in the transport cycle is not known. Here it is shown that: 1) when the [Cl-], [Br-], or pH is varied, the band 3 transport sites on both sides of the membrane behave like a homogeneous population of simple anion binding sites in 35Cl NMR experiments, and 2) when the [Cl-] is varied, the outward-facing transport site behaves like a simple anion binding site. These results indicate that the postulated inhibitory site has no effect on chloride binding to the transport site. Instead, the results are quantitatively consistent with the ping-pong model (Gunn, R. B., and Frolich, O. (1979) J. Gen. Physiol. 74, 351-374), which states that the transport site is the only site involved in the transport cycle. Expressions are derived for the macroscopically observed characteristics of a ping-pong transporter: these characteristics are shown to be weighted averages of the microscopic properties of the inward- and outward-facing conformations of the transport site. In addition to supporting the simplicity of the transport mechanism, the high pH titration curve for chloride binding to the transport site provides insight into the structure of the site. The macroscopically observed pKA = 11.1 +/- 0.1 in the leaky ghost system indicates that an arginine must provide the essential positive charge in the inward- or outward-facing conformation of the transport site, or in both conformations. PMID- 4019485 TI - The kinetic equation for the chloride transport cycle of band 3. A 35Cl and 37Cl NMR study. AB - The nature of a transmembrane transport process depends largely on the identity of the reaction that is rate-limiting in the transport cycle. The one-for-one exchange of two chloride ions across the red cell membrane by band 3 can be decomposed into two component reactions: 1) the binding and dissociation of chloride at the transport site, and 2) the translocation of bound chloride across the membrane. The present work utilizes 35 Cl NMR and 37 Cl NMR to set lower limits on the rates of chloride binding and dissociation at the saturated inward- and outward-facing band 3 transport sites (greater than or equal to 10(5) events site-1 s-1 in all cases). At both 0-3 and 37 degrees C, the NMR data specify that chloride binding and dissociation at the saturated transport sites are not rate limiting, indicating that translocation of bound chloride across the membrane is the slowest step in the overall transport cycle. Using these results, it is now possible to describe many features of the kinetic equation for the ping-pong transport cycle of band 3. This transport cycle can be decomposed into two half reactions associated with the transport of two chloride ions in opposite directions across the membrane, where each half-reaction is composed of sequential binding, translocation, and dissociation events. One half-reaction contains the rate-limiting translocation event that controls the turnover of the transport cycle; in this half-reaction, translocation must be slower than binding and dissociation. The other half-reaction contains the non-rate-limiting translocation event that in principle could be faster than binding or dissociation. However, when the following sufficient (but not necessary) condition is satisfied, both translocation events are slower than binding and dissociation: if the non-rate-limiting translocation rate is within a factor of 10(2) (0-3 degrees C) or 2 (37 degrees C) of the overall turnover rate, then translocation is rate-limiting in each saturated half-reaction. Thus, even though chloride appears to migrate through a channel that leads from the transport site to solution, the results support a picture in which the binding, dissociation, and channel migration events are rapid compared to the translocation of bound chloride across the membrane. In this case, chloride binding to the transport site can be described by a simple dissociation constant (KD = kappa OFF/kappa ON) rather than by a Michaelis-Menten constant (KM = (kappa OFF + kappa TRANSLOCATION)/KAPPA ON). PMID- 4019486 TI - Metabolism of retinoids by embryonal carcinoma cells. AB - Several embryonal carcinoma (EC) cell lines were tested in culture for their ability to metabolize all-trans-[3H]retinol, all-trans-[3H]retinyl acetate, and all-trans-[3H]retinoic acid. There was little, if any, metabolism of all-trans retinol to more polar compounds; we failed to detect conversion to acidic retinoids by reverse-phase high performance liquid chromatography and derivatization. We also did not observe [3H]retinoic acid when EC cells were incubated with [3H]retinyl acetate. Unlike the other retinoids, all-trans [3H]retinoic acid, even at micromolar levels, was almost totally modified by cells from several EC lines within 24 h. Most of the labeled products were secreted into the medium. Some EC lines metabolized retinoic acid constitutively, whereas others had an inducible enzyme system. A differentiation-defective line, which contains little or no cellular retinoic acid-binding protein activity, metabolized retinoic acid poorly, even after exposure to inducers. At least eight retinoic acid metabolites were generated; many contain hydroxyl residues. Our data lead us to propose that retinol does not induce differentiation of EC cells in vitro via conversion to retinoic acid. Also, the relatively rapid metabolism of retinoic acid by EC cells suggests either that the induction of differentiation need involve only a transient exposure to this retinoid or that one or more of the retinoic acid metabolites can also promote differentiation. PMID- 4019487 TI - Pyridoxamine-5'-phosphate oxidase exhibits no specificity in prochiral hydrogen abstraction from substrate. AB - The stereochemistry for hydrogen removal from pyridoxamine 5'-phosphate with liver pyridoxine (pyridoxamine)-5'-phosphate oxidase was examined to determine whether or not there are significant steric constraints at the substrate region of the active site of the oxidase. For this, pyridoxal 5'-phosphate was reduced with tritium-labeled sodium borohydride in ammoniacal solution to yield racemically labeled [4',4'-3H]pyridoxamine 5'-phosphate which was then chemically or enzymatically oxidized to [4'-3H]pyridoxal 5'-phosphate. This latter was used as coenzyme with either L-aspartate (L-glutamate) aminotransferase and L glutamate or L-glutamate decarboxylase and alpha-methyl-DL-glutamate to generate [4'-3H]pyridoxamine 5'-phosphate known to be labeled in the R-position. Reaction of the oxidase with the pro-R as well as the pro-R,S-labeled substrates followed by isolation of [4'-3H]pyridoxal 5'-phosphate and 3H2O revealed only half the radioactivity was abstracted from the original substrate in either case. Hence, the oxidase is not stereospecific and equally well catalyzes removal of either pro-R or pro-S hydrogen from the 4-methylene of pyridoxamine 5'-phosphate. PMID- 4019488 TI - Lipoprotein lipase hydrolysis of trioleoylglycerol in a phospholipid interface. Effect of cholesteryl oleate on catalysis. AB - The effect of cholesteryl oleate on the lipoprotein lipase-catalyzed hydrolysis of trioleoylglycerol was determined in monolayers of egg phosphatidylcholine at a constant surface pressure of 24 mN m-1. The phospholipid monolayers contained 1.0 to 7.5 mol % trioleoylglycerol and various amounts (0 to 20 mol %) of cholesteryl oleate. The initial rates of trioleoylglycerol hydrolysis were determined with lipoprotein lipase purified from bovine milk. In phospholipid monolayers containing 5.0 or 7.5 mol % trioleoylglycerol, the further addition of cholesteryl oleate caused a decrease in lipoprotein lipase activity. In contrast, addition of cholesteryl oleate to phospholipid monolayers containing 1.0 or 2.5 mol % trioleoylglycerol enhanced enzyme activity; a 3-fold enhancement was observed with 5.0-7.5 mol % cholesteryl oleate. Based on force-area measurements, the cholesteryl ester-mediated decrease in lipoprotein lipase activity observed at high substrate concentrations may be explained by displacement of trioleoylglycerol from the interface, thereby reducing the interfacial trioleoylglycerol concentration available for enzyme catalysis. One explanation for the cholesteryl oleate-mediated enhancement of lipoprotein lipase activity at low trioleoylglycerol concentrations is that the additional spreading of cholesteryl oleate disrupts microemulsions of trioleoylglycerol, thereby increasing the effective monomer substrate concentration available for enzyme catalysis. Based on these monolayer studies with model systems, we suggest that the relative amount of cholesteryl esters in plasma triacylglycerol-rich lipoproteins plays a regulatory role in determining the rate at which triacylglycerols are cleared from the circulation. PMID- 4019489 TI - Adenovirus-dependent increase in cell membrane permeability. AB - When KB cells were labeled with either 51Cr (1 microCi/ml) or [35S]methionine (5 microCi/ml) and treated with 10 micrograms/ml of adenovirus type 2 (Ad2) at pH 6.0 for 60 min at 37 degrees C, about 25% of the cell-associated 51Cr and 5% of the [35S]methionine were released into the medium. The 51Cr was mainly associated with molecules of 1500 Da or less. When KB cells were labeled with either [3H] choline, alpha-[3H]aminobutyric acid, or [3H]deoxy-2-fluoro-D-glucose and exposed to Ad2, these molecules were released in amounts much higher than 51Cr. The Ad2 dependent release of choline was found to be dependent on Ad2 concentration, with maximum release (nearly 60%) at 10 micrograms/ml of Ad2, on the length of the incubation with Ad2, with maximum release at about 90 min, and on the medium pH with maximum activity at pH 6.0 to 6.5. Greater than 95% of the choline released was water-soluble and identified as choline phosphate. Less than 5% of the choline released was associated with lipids, and none was released as a phospholipid vesicle or micelle. The ability of Ad2 to release choline was abolished by incubating Ad2 for 10 min at 45 degrees C, whereas the binding of Ad2 to the cells was not affected. Fetal calf serum also blocked Ad2-dependent choline release. PMID- 4019490 TI - Mechanism of inhibition of polypeptide chain initiation in heat-shocked Ehrlich cells involves reduction of eukaryotic initiation factor 4F activity. AB - Almost all living organisms studied respond to elevated temperature with a marked inhibition of overall protein synthesis but increased synthesis of a specific set of proteins, the so-called heat-shock proteins. We have prepared a cell-free protein synthesizing system (lysate) from heat-shocked Ehrlich ascites tumor cells that reflects the inhibition of protein synthesis in intact cells at elevated temperatures. We have isolated and partially purified a stimulator of the heat-shocked cell lysate from Ehrlich cells. Through four purification steps, the stimulator is chromatographically identical to eukaryotic initiation factor 4F (eIF-4F), an initiation factor which specifically binds mRNA cap structure. Therefore, we have tested the effects of highly purified reticulocyte eIF-4F on the heat-shocked cell lysate. Protein synthesis is strongly stimulated by addition of highly purified eIF-4F. Synthesis in the heat-shocked lysate is more inhibited at high (70 mM) KCl concentrations, than at lower concentrations, and stimulation by eIF-4F is correspondingly greater at higher KCl concentrations, so that the rate of protein synthesis is returned to control (non-heat-shocked lysate) levels at all KCl concentrations. Furthermore, at 70 mM KCl, in heat shocked lysates, synthesis of the 68-kDa heat-shock protein is much less inhibited than synthesis of the bulk of non-heat-shock proteins, and eIF-4F stimulates synthesis of 68-kDa protein to a much lesser extent than non-heat shock proteins. Thus, addition of purified eIF-4F reverses the effects of elevated temperatures on Ehrlich cells that are reflected in lysates. Therefore, we propose that the inhibition of translation in heat-shocked Ehrlich cells is the result of inactivation of eIF-4F function. PMID- 4019491 TI - Inosine analogs. Their metabolism in mouse L cells and in Leishmania donovani. AB - The growth of Leishmania donovani promastigotes and mouse L cells is differentially inhibited by several inosine analogs with modifications in the imidazole ring. The protozoal and mammalian cells also demonstrate differential metabolism of these analogs. 7-Deazainosine, 7-thia-7,9-dideazainosine, and formycin B were converted to their respective ATP analogs by both cell types. 8 Azainosine was converted to a GTP analog by mouse L cells; L. donovani did not metabolize this nucleoside. 9-Deazainosine and allopurinol riboside were metabolized only to their respective IMP analogs by L cells. L. donovani metabolized 9-deazainosine and allopurinol riboside to their ATP analogs and also metabolized 9-deazainosine to its GTP analog. All nucleosides studied were resistant to cleavage by either organism. From metabolism studies in the presence of a specific enzyme inhibitor, it was deduced that allopurinol riboside, formycin B, and 9-deazainosine were phosphorylated by at least two different routes in the mouse L cells. The metabolism of formycin B was inhibited 65% by the adenosine kinase inhibitor, 5-iodotubercidin, whereas the metabolism of allopurinol riboside (14% inhibition) and 9-deazainosine (0% inhibition) was only slightly affected by this inhibitor. The metabolism of allopurinol riboside and 9 deazainosine by L. donovani was not affected by 5-iodotubercidin. In contrast to the results of L cells, the metabolism of formycin B by L. donovani was also not affected by 5-iodotubercidin. The abilities of mouse L cells and L. donovani to metabolize these inosine analogs to the corresponding nucleotide analogs of ATP or GTP may be considered to be an activating step and correlates well with the respective cytotoxic effects of these compounds. PMID- 4019492 TI - Phospholipase A2 sensitivity of uterine smooth muscle membrane phospholipids and adenylate cyclase activity. Effect of temperature on the action of phospholipase present in excess. AB - Basal as well as GTP-dependent adenylate cyclase activity was partially resistant to porcine pancreatic phospholipase A2, although more activity was degraded at 16 than at 2 degrees C. In contrast, isoproterenol-dependent activity was completely destroyed regardless of the temperature. Snake venom phospholipase A2 destroyed approximately 90% of basal and GTP-dependent adenylate cyclase activity at all temperatures. The difference between the lipases is consistent with earlier evidence that elevated temperature facilitates the entry of some forms of phospholipase into the membrane bilayer. The temperature dependence of adenylate cyclase activation by the GTP analog Gpp[NH]p and its pancreatic phospholipase sensitivity were compared. The Arrhenius plots were markedly similar and biphasic with discontinuities at approximately 8 degrees C. The same temperature-dependent phospholipid phase transition might account, therefore, for both adenylate cyclase properties. Only small amounts of membrane phosphatidylethanolamine and phosphatidic acid were hydrolyzed by pancreatic phospholipase in a temperature dependent manner analogous to adenylate cyclase degradation. These results suggest that specific phospholipids support catalysis and adenylate cyclase activation, but that different phospholipids are required for receptor coupling which may occur in a less viscous part of the membrane. PMID- 4019493 TI - The refined crystal structure of dimeric phospholipase A2 at 2.5 A. Access to a shielded catalytic center. AB - The 2.5-A crystal structure of the calcium-free form of the dimeric venom phospholipase A2 from the Western Diamondback rattlesnake Crotalus atrox, has been refined to an R-factor of 17.8% (I greater than 2 sigma) and acceptable stereochemistry. The molecule is a nearly perfect 2-fold symmetric dimer in which most of the catalytic residues of both subunits face an internal cavity. The restricted access to the putative catalytic sites is especially puzzling as the optimal substrates for this and most other phospholipase A2 are phospholipids condensed in micellar or lamellar aggregates. We point out that substrate access to the internal cavity may be aided by calcium binding which can alter the intersubunit contacts that shield the catalytic network. We also suggest that a system of hydrogen-bonded moieties exists on the surface of the dimer that links the amino terminus to the catalytic system, through an invariant Gln 4 side chain and the backbone of the active center residue, Tyr 73. This hydrogen-bonded network is on a highly accessible surface of the dimer and would appear to contribute to the enzyme's (as opposed to the proenzyme's) special capacity to attack aggregated rather than monomeric substrate. PMID- 4019494 TI - The complete nucleotide sequence of the Xenopus laevis mitochondrial genome. AB - The complete sequence of the 17,553-nucleotide Xenopus laevis mitochondrial genome has been determined. A comparison of this amphibian mitochondrial genomic sequence with those of the mammalian mitochondrial genomes reveals a similar gene order and compact genomic organization. The encoded genes for 22 tRNAs, two ribosomal RNAs, and 13 proteins (COI, COII, COIII, ATPase 6, cytochrome b, and eight additional unidentified reading frames) in the amphibian mitochondria are highly homologous to their mammalian counterparts. Although the amphibian mitochondrial genome contains a significantly larger displacement loop region than the mammalian mitochondrial genomes, there are several regions of sequence homology near the putative sites for heavy and light strand transcription initiation and heavy strand replication. The unique mitochondrial genetic code observed in the mammalian mitochondrial systems is similar to that of the X. laevis mitochondrial genome because of the presence of only 22 encoded tRNAs and the high degree of homology between the predicted protein sequences. However, the amphibian system exclusively utilizes AUG as the start codon in all 13 open reading frames and shows a preference for codons ending in U rather than ending in C. In addition, the X. laevis mitochondrial genome employs the encoded AGA stop codon once and the UAA stop codon three times and requires polyadenylation to provide the nine other UAA stop codons. These observations suggest that the mechanisms of replication, transcription, processing, and translation in mitochondria are highly conserved throughout higher vertebrates. PMID- 4019495 TI - In vivo mobility of fatty acid end groups of Bacillus thuringiensis plasma membrane lipids during growth and sporulation. AB - The mobility of 13C specifically labeled branched chain end groups of iso-even fatty acids in intact, live Bacillus thuringiensis cells was studied by 13C nuclear magnetic resonance spectroscopy. This study apparently represents the first direct observation of branched chain carbon atoms in living cells. End groups were labeled using DL-[beta, delta, delta'-13C]valine as a precursor chain initiator for iso-even fatty acid synthesis after using L-[delta, delta'-14C]L valine to determine optimal conditions for labeling of the membrane fatty acid end groups. Cell survival in the NMR was determined for various lengths of time at 28 and 39 degrees C. Subsequently, 13C-labeled vegetative cells, sporulating cells (three stages of development), and purified mature spores were analyzed by 13C NMR using corresponding unlabeled cells as controls. Spin lattice relaxation times (T1) were obtained for the enriched iso-branched region at 23.3 ppm and for the natural abundance peak for the glycerol backbone (carbons 1 and 3) of the membrane lipids at 61.7 ppm. The T1 of the glycerol carbons (0.08 s) did not change significantly with stage of development or temperature. The T1 of the iso even enriched end group changed dramatically from vegetative cells (0.70s) to sporulating cells (0.28 s) at 28 degrees C. A decrease in the T1 was also observed at 39 degrees C from 0.91 s for vegetative cells to 0.54 s for sporulating cells. Accompanying the reduced mobility indicated by the T1 values, there was a general decline in the signal-to-noise ratios of identically acquired spectra as sporulation continued which culminated in the lack of discernible plasma membrane lipid resonances in purified mature spores. The progressive loss of signal appeared to have resulted from a continuous decline in the fraction of plasma membrane fatty acids with sufficient mobility to give signals above background. PMID- 4019496 TI - Crystallization and preliminary x-ray crystallographic data of dienelactone hydrolase from Pseudomonas sp. B13. AB - Dienelactone hydrolase (EC 3.1.1.45) from Pseudomonas sp. B13 has been crystallized in a form suitable for high resolution x-ray diffraction study. The crystals are orthorhombic, the space group being P212121, with unit cell dimensions a = 48.9 A, b = 71.2 A, and c = 77.5 A. There appears to be 1 molecule in the asymmetric unit. PMID- 4019497 TI - Comparison of the complexed and free forms of rat liver arginyl-tRNA synthetase and origin of the free form. AB - Arginyl-tRNA synthetase is found in multiple molecular weight forms in extracts from a variety of mammalian tissues. The rat liver enzyme can be isolated either as a component of the synthetase complex (Mr greater than 10(6) or as a free protein (Mr = 60,000). However, based on activity measurements after sodium dodecyl sulfate-polyacrylamide gel electrophoresis, the molecular weight of the free form differs from its counterpart in the complex (Mr = 72,000). Both forms of arginyl-tRNA synthetase cross-react with an antibody directed against the complex, and both have similar catalytic properties. Thus, the two proteins have similar apparent Km values for arginine and ATP, the same pH optimum, are inhibited equally by elevated ionic strength and PPi, and they aminoacylate the same population of tRNA molecules. On the other hand, the free and complexed forms differ with respect to their apparent Km values for tRNA (free, 4 microM; complexed, 28 microM), their temperature sensitivity (complexed greater sensitivity), and their hydrophobicity (complexed more hydrophobic). Limited proteolysis of the synthetase complex with papain releases a low molecular weight form of arginyl-tRNA synthetase whose size, temperature sensitivity, and hydrophobicity are similar to that of the endogenous free form. Nevertheless, the usual 2:1 ratio of complexed-to-free form of rat liver arginyl-tRNA synthetase is not altered by a variety of homogenization or incubation conditions in the presence or absence of multiple protease inhibitors. In contrast to extracts of rat liver, rabbit liver extracts do not contain a free form of arginyl-tRNA synthetase. These results suggest that the complexed and free forms of arginyl tRNA synthetase are probably the same gene product and that the free form in rat liver extracts is derived from the complexed form by a limited endogenous proteolysis that removes the portion of the protein required for anchoring it in the complex. The question of whether the free form is an artifact of isolation or whether it pre-exists in the cell is discussed. PMID- 4019498 TI - Structural characterization and the determination of negative cooperativity in the tight binding of 2-carboxyarabinitol bisphosphate to higher plant ribulose bisphosphate carboxylase. AB - When CO2/Mg2+-activated spinach leaf ribulose-1,5-bisphosphate carboxylase (EC 4.1.1.39) is incubated with the transition-state analog 2-carboxyarabinitol 1,5 bisphosphate, an essentially irreversible complex is formed. The extreme stability of this quaternary complex has allowed the use of native analytical isoelectric focusing, anion-exchange chromatography, and nondenaturing polyacrylamide gel electrophoresis to probe the mechanism of the binding process and the effects of ligand tight-binding on the structure of the protein molecule. Changes in the chromatographic and electrophoretic properties of the enzyme upon tight binding of the inhibitor reveal that the ligand induces a conformational reorganization which extends to the surface of the protein molecule and, at saturation, results in a 16% decrease in apparent molecular weight. Analysis of ligand binding by isoelectric focusing shows that (i) incubating the protein with a stoichiometric molar concentration of ligand (site basis) results in an apparently charge homogeneous enzyme population with an isoelectric point of 4.9, and (ii) substoichiometric levels of ligand produce differential effects on each of the charge microheterogeneous native enzyme forms. These stoichiometry dependent changes in electrofocusing band patterns were employed as a probe of cooperativity in the ligand tight-binding process. The tight-binding reaction was shown to be negatively cooperative. PMID- 4019499 TI - Zn2+-induced cooperativity of mannitol-1-phosphate dehydrogenase from Aspergillus parasiticus. AB - Mannitol-1-phosphate dehydrogenase (EC 1.1.1.17) has been purified from Aspergillus parasiticus, a filamentous fungus which produces the polyketide mycotoxin, versicolorin A. Its kinetic properties have been compared with those of mannitol-1-phosphate dehydrogenase from the related non-toxin-producing fungus, A. niger. Both enzymes are inhibited by divalent transition metals, especially Zn2+ and Cd2+, but only the enzyme from A. parasiticus exhibits inhibitor-induced cooperative binding of the substrate, fructose-6 phosphate. Double reciprocal plots (1/v versus 1/Fru-6-P) are linear in the absence of Zn2+ but in the presence of Zn2+ are concave upward, with Hill coefficients of 1.5. The extent of cooperativity is inversely related to ionic strength, disappearing at 100 mM KCl. The enzymes from both organisms are relatively stable to incubation at 30 degrees C, but only the enzyme from A. parasiticus is rendered thermally unstable by the addition of divalent transition metals. A model is proposed to explain how binding of transition metal ions affects substrate binding and thermal stability of the enzyme. PMID- 4019500 TI - (Cu,Zn)-metallothioneins from fetal bovine liver. Chemical and spectroscopic properties. AB - Two metallothioneins (MTs) from bovine fetal liver were purified by a combination of gel filtration and ion-exchange chromatography. The primary structures of the isoproteins MT-1 and MT-2 were elucidated by peptide and amino acid sequence analysis. The amino-terminal part was deduced from automated Edman degradations of the pyridylethylated CNBr-cleaved derivatives. The remaining part of the sequence was established by a comparison of the carboxamidomethylated tryptic peptides to those from equine liver MT-1A and MT-2B. Peptides differing in either amino acid composition or retention time from high pressure liquid chromatography were further subjected to manual Edman degradations or carboxypeptidase Y digestion. The two isoproteins consist of 61 amino acids and show a sequence identity of 90%. When compared with the primary structures of other mammalian MTs, the 20 cysteinyl residues are totally conserved, in agreement with their function as metal ligands. The two isoproteins contain Cu and Zn at a ratio of 3:4. Spectroscopic data reveal absorption properties typical for both Cu- and Zn thiolate transitions. The marked differences of MT-1 and MT-2 in the Cu-thiolate CD features can be attributed to the six amino acid substitutions occurring exclusively in the amino-terminal parts of the molecules. It is proposed that in bovine fetal MTs also the three copper ions are preferentially bound to the first 9 cysteinyl residues (cluster B) and the four zinc ions to the remaining 11 cysteinyl residues (cluster A) suggested previously by 113Cd NMR spectroscopy of calf liver MTs (Briggs, R. W., and Armitage, I. M. (1982) J. Biol. Chem. 257, 1259-1262). PMID- 4019501 TI - In situ cross-linking of androgen receptors to nuclear acceptor sites of rat prostate with formaldehyde. AB - Androgen receptors were attached covalently in situ to their nuclear acceptor sites with the contact site cross-linker, formaldehyde. Chromatin, prepared from sonicated nuclei of rat prostate, was labeled by isotope exchange with [3H]dihydrotestosterone and found to contain 19,000 +/- 900 (mean +/- S.E.) salt extractable androgen receptors/nucleus which sedimented in the 3-4 S region of 7.6-76% (v/v) glycerol gradients and at a density of approximately 1.28-1.35 g/ml in CsCl gradients. After incubation of the chromatin with 0.5% (w/v) formaldehyde for 1 h at 4 degrees C, there was a 90% reduction in the concentration of free androgen receptors and an increase in the density of the androgen binding sites recovered from CsCl gradients. Extensive digestion of the cross-linked chromatin with micrococcal nuclease liberated 18% of the androgen receptors as 3-4 S entities and caused an overall decrease in the density of the receptor-acceptor complexes. Ribonuclease digestions had no effect on the androgen receptors cross linked to chromatin. Mild digestion of the cross-linked preparations with trypsin, alone or in combination with micrococcal nuclease, resulted in the release of 74% and 97% of the androgen receptors, respectively. Together, these findings imply that two classes of receptor-acceptor complexes are present in prostatic chromatin--one, containing about 20% of the androgen receptors in which the receptors are in direct contact with DNA but not with proteins and the other, containing most of the androgen receptors in which the receptors are adjacent to acceptor proteins but not to DNA. PMID- 4019502 TI - Monoclonal antibodies to rabbit skeletal muscle phosphorylase kinase. Probes for studies of subunit function. AB - Monoclonal antibodies to rabbit skeletal muscle phosphorylase kinase were produced by the conventional hybridoma cell technique. 90 out of 600 hybridomas were found to produce phosphorylase kinase binding antibodies from which only five secreted also phosphorylase kinase activity affecting antibodies. Three of them were cloned; two hybridomas resisted all cloning efforts. Employing immunoblot technique all monoclonal antibodies show cross-reactivity with the alpha, beta, and gamma subunits of phosphorylase kinase indicating that similar, if not identical, epitopes are present on these three subunits. No cross reactivity with delta is observed. Monoclonal antibodies secreted by two clones which bind to the alpha subunit stimulate the Ca2+-independent A0 activity of phosphorylase kinase more than 30-fold, whereas all other monoclonal antibodies obtained are ineffective in this respect. Monoclonal antibodies binding to the beta subunit inhibit the Ca2+-dependent activities significantly. Antibody produced by one hybridoma binds to the alpha, beta, and gamma subunits with approximately the same affinity. Based on the dual function of calmodulin in phosphorylase kinase (Hessova, Z., Varsanyi, M., and Heilmeyer, L.M.G., Jr. (1985) Eur. J. Biochem. 146, 107-115) we conclude that binding of anti-alpha monoclonal antibodies to a regulatory domain in the alpha subunit results in an uncoupling of the inhibitory function of the Ca2+-free delta from the holoenzyme which leads to a concomitant increase in A0 activity. Furthermore, binding of anti-beta monoclonal antibodies to the beta subunit prevents a signal transfer from the Ca2+-saturated delta to the catalytic site of the holoenzyme which inhibits the Ca2+-dependent activities. PMID- 4019503 TI - Pituitary enzyme conversion of putative synthetic oxytocin precursor intermediates. AB - Neurosecretory granule lysate from bovine posterior pituitary was shown to contain both carboxypeptidase B and amidating activities. The former sequentially releases COOH-terminal basic residues from the oxytocin biosynthetic precursor fragment oxytocinyl-GKR (CYIQNCPLGKR) to form oxytocinyl-GK and then oxytocinyl G. The amidating enzyme converts the resulting oxytocinyl-G into oxytocin (CYIQNCPLG-NH2). The carboxypeptidase B was separated from a less specific carboxypeptidase present in granule lysate by gel filtration on Sephacryl S-300. Percoll density gradient centrifugation (after preliminary differential centrifugation) also yielded granule fractions enriched in the specific carboxypeptidase B activity. The carboxypeptidase B which converts the oxytocinyl peptides showed a fairly sharp pH dependence with an optimum of 5.5-6, was activated by cobalt ion, and was inhibited by cupric ion, EDTA, and a thiol protease inhibitor, p-chloromercuribenzoate. The amidating activity which converts oxytocinyl-G to oxytocin was competed by degradation due to proteases and/or peptidases present in lysate of Percoll gradient-derived granules. Oxytocinyl-GKR was shown by analytical affinity chromatography to bind noncovalently to neurophysin with an affinity close to that of mature oxytocin. This binding activity and the observation of carboxypeptidase B activity in the presence of large concentrations of neurophysin are consistent with the view that the exoproteolytic processing and amidation steps which occur after initial endoproteolysis of pro-oxytocin/neurophysin likely take place on oxytocin intermediate peptides which are bound in noncovalent complexes with the neurophysin domain from the precursor. PMID- 4019504 TI - Reinvestigation of the inhibition of actin polymerization by profilin. AB - In buffer containing 50 mM KCl, 1 mM MgCl2, 1 mM EGTA, 5 mM imidazole, pH 7.5, 0.1 mM CaCl2, 0.2 mM dithiothreitol, 0.01% NaN3, and 0.2 mM ATP, the KD for the formation of the 1:1 complex between Acanthamoeba actin and Acanthamoeba profilin was about 5 microM. When the actin was modified by addition of a pyrenyl group to cysteine 374, the KD increased to about 40 microM but the critical concentration (0.16 microM) was unchanged. The very much lower affinity of profilin for modified actin explains the anomalous critical concentrations curves obtained for 5-10% pyrenyl-labeled actin in the presence of profilin and the apparently weak inhibition by profilin of the rate of filament elongation when polymerization is quantified by the increase in fluorescence of pyrenyl-labeled actin. Light scattering assays of the polymerization of unmodified actin in the absence and presence of profilin gave a similar value for the KD (about 5-10 microM) when determined by the increase in the apparent critical concentration of F-actin at steady state at all concentrations of actin up to 20 microM and by the inhibition of the initial rates of polymerization of actin nucleated by either F-actin or covalently cross-linked actin dimer. In the same buffer, but with ADP instead of ATP, the critical concentration of actin was higher (4.9 microM) and the KD of the profilin-actin complex was lower for both unmodified (1-2 microM) and 100% pyrenyl-labeled actin (4.9 microM). PMID- 4019505 TI - Modification of bovine kidney pyruvate dehydrogenase kinase activity by CoA esters and their mechanism of action. AB - The activation of pyruvate dehydrogenasea kinase activity by CoA esters has been further characterized. Half-maximal activation of kinase activity was achieved with about 1.0 microM acetyl-CoA after a 20-s preincubation in the presence of NADH. More than 80% of the acetyl-CoA was consumed during this period in acetylating sites in the pyruvate dehydrogenase complex as a result of the transacetylation reaction proceeding to equilibrium. At 1.0 microM acetyl-CoA, this resulted in more than a 4-fold higher level of CoA than residual acetyl-CoA. Activation of kinase activity could result either from acetylation of specific sites in the complex or tight binding of acetyl-CoA. Removal of CoA enhanced both acetylation and activation, suggesting acetylation mediates activation. For allosteric binding of acetyl-CoA to elicit activation, an activation constant, Ka, less than 50 nM would be required. To further distinguish between those mechanisms, the effects of other CoA esters as well as the reactivity of most of the effective CoA esters were characterized. Several short-chain CoA esters enhanced kinase activity including (in decreasing order of effectiveness) malonyl CoA, acetoacetyl-CoA, propionyl-CoA, and methylmalonyl-CoA. Butyryl-CoA inhibited kinase activity as did high concentrations of long-chain acyl-CoAs. Inhibition by long-chain acyl-CoAs may result, in part, from detergent-like properties of those esters. Malonyl-CoA, propionyl-CoA, butyryl-CoA, and methylmalonyl-CoA, obtained with radiolabeled acyl groups, were shown to acylate sites in the complex. Propionyl-CoA and butyryl-CoA were tested, in competition with acetyl-CoA or pyruvate, as alternative substrates for acylation of sites in the complex and as competitive effectors of kinase activity. Propionyl-CoA alone rapidly acylated sites in the complex at low concentrations, and low concentrations of propionyl CoA were effective in activating kinase activity although only a relatively small activation was observed. When an equivalent level (20 microM) of acetyl-CoA and propionyl-CoA was used, marked activation of kinase activity due to a dominant effect of acetyl-CoA was associated with acetylation of a major portion of sites in the complex and with a small portion undergoing acylation with propionyl-CoA. Those results were rapidly achieved in a manner independent of the order of addition of the two CoA esters. That indicates that tight slowly reversible binding of acetyl-CoA is not involved in kinase activation. High levels of propionyl-CoA greatly reduced acetylation by acetyl-CoA and nearly prevented activation of kinase activity by acetyl-CoA.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 4019506 TI - Heparin and ionic strength-dependent conversion of antithrombin III from an inhibitor to a substrate of alpha-thrombin. AB - The stoichiometry of antithrombin III (AT) inhibition of alpha-thrombin (T) has been investigated in the presence and absence of heparin as a function of ionic strength by quantitative titration of enzyme active sites. In contrast to the ionic strength-independent stoichiometry of 1.0 mol of AT/mol of T observed in the absence of heparin, the presence of high-affinity heparin (HAH) resulted in an ionic strength-dependent increase in the apparent stoichiometry of inhibition from a molar ratio of 1.1 AT/T at an ionic strength of 0.3 to 9.8 mol of AT/T when the ionic strength was lowered to 0.01. Reduced sodium dodecyl sulfate polyacrylamide gel electrophoresis of the reaction products revealed that the increased AT/T stoichiometry was due to preferential formation of a specific proteolytically cleaved form of AT that was indistinguishable from the previously characterized reactive site-cleaved AT (ATM). Using high-performance liquid chromatography and sodium dodecyl sulfate-polyacrylamide gel electrophoresis to quantitate ATM, the cleaved inhibitor was shown to be formed rapidly and concomitant with the stable thrombin-antithrombin complex (TAT) and quantitatively accounted for the apparent increase in reaction stoichiometry at low ionic strength in the presence of HAH. The levels of HAH required to produce maximum ATM were catalytic at mu greater than or equal to 0.15, but became stoichiometric as the ionic strength decreased below 0.1. Substantially less ATM was produced in the presence of low-affinity heparin, while a low molecular weight HAH, virtually inactive in accelerating T inhibition by AT, was unable to promote significant ATM formation. These results indicate competition between substrate and inhibition reactions of AT with T which are affected by an ionic strength-dependent heparin interaction. A reaction mechanism accounting for these observations is proposed. PMID- 4019507 TI - Characterization of the kinetic pathway for liberation of fibrinopeptides during assembly of fibrin. AB - The time dependence of the release of fibrinopeptides from fibrinogen was studied as a function of the concentration of fibrinogen, thrombin, and Gly-Pro-Arg-Pro, an inhibitor of fibrin polymerization. The release of fibrinopeptides during fibrin assembly was shown to be a highly ordered process. Rate constants for individual steps in the formation of fibrin were evaluated at pH 7.4, 37 degrees C, gamma/2 = 0.15. The initial event, thrombin-catalyzed proteolysis at Arg-A alpha 16 to release fibrinopeptide A (kcat/Km = 1.09 X 10(7) M-1s-1) was followed by association of the resulting fibrin I monomers. Association of fibrin I was found to be a reversible process with rate constants of 1 X 10(6) M-1s-1 and 0.064 s-1 for association and dissociation, respectively. Assuming random polymerization of fibrin I monomer, the equilibrium constant for fibrin I association (1.56 X 10(7) M-1) indicates that greater than 80% of the fibrin I protofibrils should contain more than 10 monomeric units at 37 degrees C, pH 7.4, when the fibrin I concentration is 1.0 mg/ml. Association of fibrin I monomers was shown to result in a 6.5-fold increase in the susceptibility of Arg-B beta 14 to thrombin-mediated proteolysis. The 6.5-fold increase in the observed specificity constant from 6.5 X 10(5) M-1s-1 to 4.2 X 10(6) M-1s-1 upon association of fibrin I monomers and the rate constant for fibrin association indicates that most of the fibrinopeptide B is released after association of fibrin I monomers. The interaction between a pair of polymerization sites in fibrin I dimer was found to be weaker than the interaction of fibrin I with Gly Pro-Arg-Pro and weaker than the interaction of fibrin I with fibrinogen. PMID- 4019508 TI - Peroxidase-catalyzed formation of triplet acetone and chemiluminescence from isobutyraldehyde and molecular oxygen. AB - It has been established that the horseradish peroxidase/O2/isobutyraldehyde (IBAL) system leads to triplet acetone and formic acid formation followed by phosphorescence of the triplet acetone (see, for example, Bechara, E.J.H., Faria Oliveira, O.M.M., Duran, N., Casadei de Baptista, R., and Cilento, G. (1979) Photochem. Photobiol. 30, 101-110). In this paper many of the mechanistic details are established. The reaction is initiated by the autoxidation of IBAL to form the peracid (CH3)2CHC = O(OOH). The peracid converts horseradish peroxidase into compound I which in turn is converted into compound II by abstracting the alcoholic hydrogen atom from the enol form of IBAL. This creates a free radical with two resonance forms. (Formula: see text) Addition of molecular oxygen to the latter resonance form creates a peroxy radical which abstracts a hydrogen atom near the active site of the enzyme. The newly formed alpha-peroxide in turn forms a dioxetane-type of intermediate which rapidly decomposes into triplet acetone and formic acid. Compound II reacts with the enol by the same pathway as compound I. Thus native horseradish peroxidase is regenerated. The hydrogen atom abstraction near the enzyme active site may occur directly from ethanol, present to solubilize IBAL or from a group on the enzyme, in which case ethanol participates in a repair mechanism. Phosphate buffer is necessary because it catalyzes the keto-enol conversion of IBAL. Thus horseradish peroxidase participates in a normal peroxidatic cycle. The only chain reaction is the uncatalyzed autoxidation of IBAL, most of which occurs prior to the mixing of IBAL with the oxygenated horseradish peroxidase solution. PMID- 4019509 TI - Differential stereoselectivity of cytochromes P-450b and P-450c in the formation of naphthalene and anthracene 1,2-oxides. The role of epoxide hydrolase in determining the enantiomer composition of the 1,2-dihydrodiols formed. AB - As is the case for cytochrome P-450c, arene 1,2-oxides have been identified as initial metabolites when naphthalene and anthracene are oxidized by cytochrome P 450b in a highly purified, reconstituted system. Overall rates of metabolism by cytochrome P-450b are greater than 3-fold and greater than 50-fold lower than the respective rates of metabolism by cytochrome P-450c. For both hydrocarbons, the ( )-(1S,2R)-oxide predominates (74%) with cytochrome P-450b as the terminal oxidant, based on trapping the labile arene oxides as N-acetyl-L-cysteine S conjugates of known absolute configuration. This result is in marked contrast to data obtained with cytochrome P-450c where the (+)-(1R,2S)-oxides predominate (73 greater than 95%). In the absence of added epoxide hydrolase, the metabolically formed arene oxides rapidly isomerize to phenols. Addition of increasing amounts of epoxide hydrolase to the incubation medium results in the formation of trans 1,2-dihydrodiols at the expense of phenols from the common arene oxide intermediates. Evaluation of the kinetic parameters (Km and kcat) for the hydration of the (+)- and (-)-enantiomers of both arene oxides by epoxide hydrolase has indicated that the (+)-(1R,2S)-enantiomers exhibit lower values of Km (approximately 1 microM) whereas the values of kcat are similar for both enantiomers of a given arene oxide. These parameters have allowed construction of a mathematical model which predicts the enantiomer composition of the dihydrodiols formed from naphthalene in reconstituted systems containing specific epoxide hydrolase concentrations. The data reported argue against a selective functional coupling mechanism between cytochrome P-450c and epoxide hydrolase in the metabolism of naphthalene and anthracene to the 1,2-dihydrodiols. PMID- 4019510 TI - Studies of synthetic peptide analogs of the amphipathic helix. Structure of complexes with dimyristoyl phosphatidylcholine. AB - The amphipathic helix hypothesis for the lipid-associating domains of exchangeable plasma apolipoproteins has been further studied by analysis of the structure of the complexes formed between four synthetic peptide analogs of the amphipathic helix and dimyristoyl phosphatidylcholine (DMPC). Density gradient ultracentrifugation, negative stain electron microscopy, nondenaturing gradient gel electrophoresis, 1H NMR, high sensitivity differential scanning calorimetry, and circular dichroism were the techniques used in these studies. The two analogs Asp-Trp-Leu-Lys-Ala-Phe-Tyr-Asp-Lys-Val-Ala-Glu-Lys-Leu-Lys-Glu-Ala-Phe (18A) and 18A-Pro-18A whose sequences most strongly mimic native amphipathic sequences were found also most strongly to mimic apolipoprotein A-I in DMPC complex structure. The covalently linked dimer of the prototype amphipathic analog 18A, 18A-Pro-18A, appears to have greater lipid affinity than 18A. This presumably is the result of the cooperativity provided by two covalently linked lipid-associating domains in 18A-Pro-18A. The studies further suggest that the charge-reversed analog of the prototype 18A, reverse-18A, has the lowest lipid affinity of the four analogs studied and forms only marginally stable discoidal DMPC complexes. We postulate that this low lipid affinity is due predominantly, but not necessarily exclusively, to the lack of a hydrophobic contribution of lysine residues at the polar-nonpolar interface of reverse-18A versus 18A. The intermediate lipid affinity of des-Val10-18A, the fourth analog peptide, to produce a rank order of 18A-Pro-18A greater than 18A greater than des-Val10-18A greater than reverse-18A, supports this interpretation. Des-Val10-18A which has Val deleted from 18A has an amphipathic helical structure partially disrupted by the shift of 2 lysine residues away from the polar-nonpolar interface. PMID- 4019511 TI - Studies of synthetic peptide analogs of the amphipathic helix. Correlation of structure with function. AB - The four peptide analogs of the amphipathic helix whose interactions with dimyristoyl phosphatidylcholine were described in the preceding paper were compared with apolipoproteins (apo) A-I and A-II in ability to displace native apolipoprotein from high density lipoprotein (HDL) and in ability to activate lecithin:cholesterol acyltransferase. The rank order of the ability of the four peptide analogs to displace apo-A-I from intact HDL was 18A-Pro-18A greater than 18A greater than des-Val10-18A greater than reverse-18A, the same order suggested in the preceding paper for relative lipid affinities. Modified HDL from which 40% of the apo-A-I had been displaced by 18A was indistinguishable from unmodified HDL in its ability to act as a lecithin:cholesterol acyltransferase substrate. This suggests that the easily displaced apo-A-I molecules in polydisperse HDL are relatively ineffectual as lecithin:cholesterol acyltransferase activators and/or 18A replaces the lecithin:cholesterol acyltransferase activity lost. The peptide analog 18A-Pro-18A was found to be a powerful activator of lecithin:cholesterol acyltransferase when incubated with unilamellar egg phosphatidylcholine (PC) vesicles, reaching 140% of the activity of apo-A-I at a 1:1.75 peptide-to-egg PC ratio. In another experiment, it was found that discoidal egg PC complexes of 18A Pro-18A, 18A, and des-Val10-18A, formed by cholate dialysis, had 30-45% of the activity of apo-A-I/egg PC discoidal complexes, also formed by cholate dialysis, at the same peptide/lipid weight ratio. Examination of the structures formed when the 18A-Pro-18A peptide was incubated with unilamellar egg PC vesicles indicated that the ability of 18A-Pro-18A to exceed apo-A-I in lecithin:cholesterol acyltransferase activating ability is due to the spontaneous conversion by 18A Pro-18A of egg PC vesicles to small protein annulus-bilayer disc structures. Apo A-I, apo-A-II, nor any of the other three peptide analogs of the amphipathic helix studied were able to convert a significant fraction of egg PC unilamellar vesicles to discoidal structures. PMID- 4019512 TI - Preliminary crystallographic study of the Fab fragments of two monoclonal anti-2 phenyloxazolone antibodies. AB - We report on the preparation, crystallization, and preliminary x-ray crystallographic study of the Fab fragments of two monoclonal anti-2 phenyloxazolone antibodies obtained from the secondary response to this hapten. The Fab fragment from one of these (NQ10/12.5) has been crystallized from polyethylene glycol 8000 solutions in a form suitable for high-resolution x-ray crystallographic studies. These crystals are monoclinic, space group C2, with a = 129.2 A, b = 79.4 A, c = 57.7 A, beta = 96.2 degrees, and one Fab/asymmetric unit. Determination of the three-dimensional structure of Fab NQ10/12.5 should help clarify the role of somatic mutation in the maturation of an immune response. This antibody and an anti-lysozyme antibody also under study apparently use the same germ-line encoded VK and a similar VH gene, respectively, as the idiotypic anti-oxazolone antibodies characteristic of the primary response. A comparative study of the two structures should shed light on the role of the pairing of heavy and light chains in the antigen-binding function of antibodies. PMID- 4019513 TI - Functional size of rat hepatic 3-hydroxy-3-methylglutaryl coenzyme A reductase as determined by radiation inactivation. AB - The functional molecular weight of rat liver 3-hydroxy-3-methylglutaryl-CoA reductase was determined by radiation inactivation. Both isolated hepatic microsomes and primary hepatocytes were irradiated with high energy electrons at 135 degrees C, and the residual microsomal enzyme activity was subsequently determined. The loss of enzyme activity in both irradiated microsomes and microsomes isolated from irradiated hepatocytes followed a single exponential decay which corresponded to a molecular mass of 200 kDa. This minimal molecular size of the functional enzyme was unaffected by either addition of cholestyramine to the rat diet or addition of 25-hydroxycholesterol plus mevalonate to the isolated rat hepatocytes. In addition, surviving enzyme protein was determined by immunoprecipitation of radiolabeled enzyme from hepatocytes that had been incubated with [35S]methionine before irradiation. The target size for loss of the monomer subunits was 98 kDa. The simplest interpretation of these results is that rat liver 3-hydroxy-3-methylglutaryl-CoA reductase in situ is a noncovalently linked dimer of the Mr = 97,200 enzyme subunit. PMID- 4019514 TI - Isolation and reconstitution of the n-butylmalonate-sensitive dicarboxylate transporter from rat liver mitochondria. AB - The mitochondrial dicarboxylate carrier has been substantially purified from rat liver mitoplasts by extraction with Triton X-114 in the presence of cardiolipin followed by chromatography on hydroxylapatite. Upon incorporation of the hydroxylapatite eluate into phospholipid vesicles, an n-butylmalonate-sensitive malonate/malate exchange has been demonstrated. This exchange activity is enhanced 226-fold relative to the starting material (i.e. detergent-extracted mitoplasts). Silver-stained sodium dodecyl sulfate-polyacrylamide gradient gels verify the high purity of this fraction relative to the starting material. Nonetheless, the banding pattern indicates that several protein species are still present. As isolated, the dicarboxylate transporter is rather unstable but can be stabilized either by the addition of 10% ethylene glycol and subsequent storage at -20 degrees C or by incorporation into phospholipid vesicles in the presence of malate followed by freezing in liquid nitrogen. Such proteoliposomes catalyze a [14C]malonate uptake which is characterized by a first order rate constant of 1.02 min-1 and a t 1/2 of 41 s. This uptake can be inhibited by dicarboxylates (e.g. succinate, malate, unlabeled malonate) but not by either alpha ketoglutarate or by tricarboxylates (e.g. citrate, threo-Ds-isocitrate). Furthermore, the reconstituted malonate transport is dependent on internal malate and can be inhibited by n-butylmalonate, mersalyl, p-chloromercuribenzoate, and Pi, but not by N-ethylmaleimide. It is concluded that this highly purified fraction contains a reconstitutively active dicarboxylate transporter which, based on its substrate specificity and inhibitor sensitivity, appears to be identical to the native dicarboxylate transport system found in intact rat liver mitochondria. PMID- 4019515 TI - Changes in protein phosphorylation during the cell cycle of Chinese hamster ovary cells. AB - The phosphorylation patterns of proteins were examined during the cell cycle of Chinese hamster ovary cells. This was accomplished by labeling synchronized cells at various times with [32P]orthophosphate and separating the proteins by both isoelectric focusing and nonequilibrium pH gradient two-dimensional gel electrophoresis. The most dramatic changes occurred during late G2/M when approximately eight proteins (including vimentin, lamin B, and histones 1 and 3) showed increased phosphorylation. Ten other proteins appeared to be uniquely phosphorylated during late G2/M. Of these 10 proteins, seven were no longer phosphorylated shortly after mitosis. There is also at least one protein which showed a relative decrease in phosphorylation during late G2/M. PMID- 4019516 TI - Primary structure of human plasma fibronectin. Characterization of a 31,000 dalton fragment from the COOH-terminal region containing a free sulfhydryl group and a fibrin-binding site. AB - The 31-kDa domain of human plasma fibronectin has been completely characterized. This fragment is located at the COOH-terminal end of the molecule immediately preceding the 3-kDa interchain disulfide-containing peptide. The 31-kDa domain was obtained after trypsin digestion of fibronectin and purified by affinity chromatography on gelatin- and heparin-Sepharose columns. The fragment eluted in the heparin-unbound fraction and was further purified by DEAE-cellulose and high performance liquid chromatography. The 31-kDa fragment contained a fibrin-binding site (fibrin II site) which was only active at physiological NaCl concentrations and therefore differed from that located in the NH2-terminal domain which also bound at lower NaCl concentrations. The 31-kDa domain bound to thiopropyl Sepharose and was shown to contain a free sulfhydryl group located at position 35 in the sequence. To determine the complete amino acid sequence of this fragment, a trypsin digestion was performed on the reduced and alkylated 31-kDa domain, and the 17 resulting peptides were isolated by high performance liquid chromatography; their amino acid compositions and amino acid sequences have been determined, and the arrangement of peptides was achieved by comparison with the sequences deduced from human and rat cDNA clones and with a related plasmic fragment from bovine fibronectin. Comparison of these three sequences showed 23 amino acid differences between human and rat fibronectin and 16 between human and bovine fibronectin. This represents a 91 and 94% homology, respectively. An interesting finding is that the 31-kDa fragment contains a deletion of 31 residues when compared to the rat cDNA sequence. This deletion appears to represent a species difference since it is due to a shorter mRNA in the case of human fibronectin. PMID- 4019517 TI - Regulation of protein phosphorylation of the intermediate-sized filament vimentin in the ciliary epithelium of the mammalian eye. AB - The intermediate-sized filaments of vimentin-type (Mr = 57,000) have been identified biochemically and immunochemically as a major cytoskeleton component in the ciliary epithelium of the mammalian eye. When human or rabbit ciliary processes, or cultured ciliary epithelial-derived cells were incubated in serum free medium containing [32P]orthophosphate and any of the following agents: 1) beta-adrenergic agonists (isoproterenol or epinephrine), 2) direct activators of adenylate cyclase (cholera toxin or forskolin), 3) analogs of cyclic AMP (8-Br cAMP), or 4) prostaglandin E1, the phosphorylation of vimentin was significantly enhanced. The maximal enhancement ranged, in vivo and in vitro, from about 3-fold in human to 5-fold in rabbit, with either 1 mM 8-Br-cAMP or 0.1 microM forskolin. Phosphorylation of vimentin increased in the presence of beta-adrenergic agonists and could be blocked by the antiglaucoma beta-adrenergic antagonist timolol. The alpha-adrenergic agonist phenylephrine had no effect on phosphorylation of vimentin. Indirect immunofluorescence microscopy using a monoclonal antibody, anti-vimentin, allowed the localization of vimentin filaments in cultured ciliary epithelial cells. Treatment of these cells in culture with the catecholamine hormone, isoproterenol (1 microM), resulted in a profound reorganization of vimentin filaments. This may be correlated with the enhanced levels of phosphorylated vimentin observed upon increasing cellular cyclic AMP. PMID- 4019518 TI - Regulation of 3-hydroxy-3-methylglutaryl coenzyme A reductase synthesis by a non sterol mevalonate-derived product in Mev-1 cells. Apparent translational control. AB - A somatic cell mutant (Mev-1) auxotrophic for mevalonate by virtue of a complete lack of detectable 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) synthase activity has been shown to demonstrate a requirement for a non-sterol mevalonate derived product for regulation of synthesis of HMG-CoA reductase. A comparison of the effects of 25-hydroxycholesterol and the combination of 25-hydroxycholesterol and mevalonate on HMG-CoA reductase activity, synthesis, and mRNA levels in Mev-1 is presented in this report. The results show a close correlation between activity, rate of synthesis, and mRNA levels for Mev-1 cells treated with 25 hydroxycholesterol alone. Under the conditions of these experiments these effects are relatively small (approximately a 4-fold decrease). A much larger inhibition of HMG-CoA reductase activity and rate of synthesis (approximately 50-fold) is observed upon treatment of Mev-1 cells with a combination of 25 hydroxycholesterol and mevalonate. Yet, under these conditions mRNA levels are still reduced by only a factor of 4. These results are interpreted to suggest that the non-sterol mevalonate-derived regulatory product of HMG-CoA reductase acts by a translational control mechanism. PMID- 4019519 TI - On the multiplicity of rat liver glutathione S-transferases. AB - Rat liver glutathione S-transferases have been purified to apparent electrophoretic homogeneity by S-hexylglutathione-linked Sepharose 6B affinity chromatography and CM-cellulose column chromatography. At least 11 transferase activity peaks can be resolved including five Yb size homodimeric isozymes, two Yc size homodimeric isozymes, one Ya homodimeric isozyme, one Y alpha homodimeric isozyme, and two Ya-Yc heterodimeric isozymes. Distribution of the GSH peroxidase activity among the CM-cellulose column fractions suggests the existence of further multiplicity in this isozyme family. Substrate specificity patterns of the Yb subunit isozymes revealed a possibility that each of the five Yb containing isozymes is composed of a different homodimeric Yb size subunit composition. Our findings on the increasing multiplicity of glutathione S transferase isozymes are consistent with the notion that multiple isozymes of overlapping substrate specificities are required to detoxify a multitude of xenobiotics in addition to serving other important physiological functions. PMID- 4019520 TI - Stimulation by epinephrine of the membrane transport of long chain fatty acid in the adipocyte. AB - In isolated rat adipocytes, epinephrine rapidly stimulates the transport of long chain fatty acid across the plasma membrane. At a concentration of unbound oleate of 0.1 microM ([fatty acid]/[albumin] = 1) and 5 min exposure to the hormone, the minimal effective concentration of epinephrine is 0.03 and the optimal concentration 0.3 microM (0.01 and 0.1 microgram/ml). The stimulated rates are 5 10-fold the basal rate of influx or efflux. The hormone effect is on the transport process specifically as shown by isolation of the product of transport in either direction as unesterified fatty acid and inhibition by the transport inhibitors phloretin and 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid. This effect of epinephrine on transport coordinates physiologically with lipase activation to bring about fatty acid release from adipose tissue. PMID- 4019521 TI - Why does Coomassie Brilliant Blue R interact differently with different proteins? A partial answer. AB - Dimethyl sulfoxide was found to be effective for extraction of Coomassie Brilliant Blue R-250 (Coomassie R) from stained proteins on polyacrylamide gel slices. A good correlation was found between the ability of different proteins to bind Coomassie R and their capacity for interaction with Coomassie Brilliant Blue G-250 (Coomassie G) in solution. Scatchard analysis showed that the number of Coomassie R ligands bound to each protein molecule is approximately proportional to the number of positive charges on the protein, about 1.5-3 dye molecules/charge. PMID- 4019522 TI - The phosphate diester linkage of the peptidoglycan polysaccharide moieties of Micrococcus lysodeikticus cell wall. AB - The external polysaccharide is a major component of Micrococcus lysodeikticus cell wall and displays distinct composition. The complete structure of the external polysaccharide had been elucidated as a basis for investigation of the cell wall structure-function relation. However, the mode of attachment of the polysaccharide to the peptidoglycan through a phosphodiester was not clear due to limitations in structural and biosynthetic studies. The present study describes purification of a lysozyme-resistant nondialyzable high-molecular-weight fragment of cell wall and identifies the sugar, D-glucose, as the point of external polysaccharide attachment to the peptidoglycan through a phosphate diester. Kinetic studies for the acid-catalyzed release of external polysaccharide from the peptidoglycan were performed in parallel with synthetic [methyl-2-acetamido-3 O-(D-1-carboxyethyl)-2-deoxy-alpha-D- glucopyranoside-6-yl]-alpha-D glucopyranosyl phosphate and alpha-D-glucopyranosyl phosphate and showed the presence of a phosphodiester linkage between external polysaccharide and peptidoglycan. In addition, type of phosphate residue and cross-linking between muramic acid and protein part have been determined. PMID- 4019523 TI - Interaction of peristaltic flow with pulsatile flow in a circular cylindrical tube. AB - The effect of pulsatile flow on peristaltic transport in a circular cylindrical tube is analysed. The flow of a Newtonian viscous incompressible fluid in a flexible circular cylindrical tube on which an axisymmetric travelling sinusoidal wave is imposed, is considered. The initial flow in the tube is induced by an arbitrary periodic pressure gradient. A perturbation solution with amplitude ratio (wave amplitude/tube radius) as a parameter is obtained when the frequency of the travelling wave and that of the imposed pressure gradient are equal. The interaction effects of periodic wall induced flow and periodic pressure imposed flow are visualized through the presence of substantially different components of steady and higher harmonic oscillating flow in the first order flow solution. Numerical results show a strong variation of steady state velocity profiles with boundary wave number and Reynolds number and a strong phase shift behaviour of the flow in the radial direction. PMID- 4019524 TI - A microcomputer controlled snow ski binding system--I. Instrumentation and field evaluation. AB - This paper presents the design and field evaluation of the first microcomputer controlled ski binding system. This system incorporates an Intel 8086 microcomputer controller and an integral binding/dynamometer. This instrumentation system not only undertakes real time control, but also it records dynamometer data via a miniature digital cassette tape recorder. The integral binding/dynamometer offers the same operational and mounting convenience of commercially available mechanical bindings. The binding may be released either manually or electrically via the controller. Comprised of four octagonal half strain rings, the strain gage dynamometer measures the three moment load components at the boot. To enable the user to conveniently operate the computer, extensive operating software was developed. The operating software is discussed in relation to both the acquisition and storage of data from the dynamometer and the control of the electro-mechanical snow ski binding. The binding system has been used successfully to both record boot moment components and control ski binding release during actual skiing maneuvers. Moment histories typical of three common recreational skiing maneuvers are presented. PMID- 4019525 TI - A microcomputer controlled snow ski binding system--II. Release decision theories. AB - A hierarchy of release decision theories for both tibia fracture and knee ligamentous injury are defined and simulated on a computer. Moment loading data, recorded during actual skiing by the microcomputer-based ski binding system described in Part I, are processed by the various release decision theories. At the bottom of the hierarchy is the simplest theory which treats boot loading as quasi-static and compares moment components to threshold levels. Another stage of the hierarchy defines an analytic expression for a combined loading failure locus. Note that this is the first formulation of a combined loading release decision theory. Yet another stage of the hierarchy computes bone moments via dynamic system leg models. The various release decision theories are evaluated by comparing processed results to both pain and bone failure limits. For the data generated by the field tests conducted to date, the simplest release decision theory satisfied the retention requirement for pain limits in the presence of muscle activity for both torsion and forward bending. For pain limits in the absence of muscle activity the retention requirement was not satisfied however. Another result is that leg dynamics are significant. A final result is that combined loading considerations lead to a more conservative theory. PMID- 4019526 TI - A new method for finite element simulation of orthodontic appliance-teeth periodontium-alveolus system. AB - This paper describes a new simulation method to analyze the initial behavior of the total system comprising orthodontic appliance, teeth, and their supporting structures. It is based on a finite element method which additionally takes account of a rotational degree of freedom. Beam and rod elements are used for finite element idealization of orthodontic appliance. Through spring elements it is connected with the teeth supported by the alveolar structures. The technique of 'initial strain' is introduced so as to analyze the effects of a gable bend and activation on the force system which is delivered by the orthodontic appliance. As compared with the photoelastic technique hitherto used, this method serves to investigate systematically and quantitatively the initial aspect of orthodontic tooth movement. PMID- 4019527 TI - Fatigue of immature baboon cortical bone. AB - Strain-controlled uniaxial fatigue and monotonic tensile tests were conducted on turned femoral cortical bone specimens obtained from baboons at various ages of maturity. Fatigue loading produced a progressive loss in stiffness and an increase in hysteresis prior to failure, indicating that immature primate cortical bone responds to repeated loading in a fashion similar to that previously observed for adult human cortical bone. Bone fatigue resistance under this strain controlled testing decreased during maturation. Maturation was also associated with an increase in bone dry density, ash fraction and elastic modulus. The higher elastic modulus of more mature bone meant that these specimens were subjected to higher stress levels during testing than more immature bone specimens. Anatomical regions along the femoral shaft exhibited differences in strength and fatigue resistance. PMID- 4019528 TI - Predominant sensitivity to tyramine in the isolated intermediate auricular artery of the dog. AB - Using a steel cannula inserting method, the action of tyramine on segments of similar size from isolated intermediate auricular and mesenteric arteries of the dog was investigated. In intermediate auricular arteries, intra-luminally administered tyramine caused strong vasoconstriction, i.e. the threshold dose for inducing constriction was about 0.03 to 0.1 micrograms and at a dose of 3 micrograms the tyramine-induced increase in perfusion pressure was usually more than 200 mm Hg. On the other hand, in mesenteric arteries, tyramine caused only a small increase in perfusion pressure, i.e. the threshold dose was about 1 to 3 micrograms and the maximum level of the increase in perfusion pressure was only 15 to 30 mm Hg even at the large dose of 100 micrograms. The tyramine-induced constriction was blocked by pretreatment with imipramine. Potassium chloride induced constriction was not inhibited by imipramine in doses which markedly suppressed tyramine-induced responses. Imipramine failed to potentiate the effects of noradrenaline but rather suppressed them in a dose-related manner in both arteries. In intermediate auricular arteries from reserpine-pretreated dogs, the effect of tyramine was attenuated whilst that of noradrenaline was significantly enhanced. Both arterial preparations responded well to periarterial electrical nerve stimulation but at lower stimulus frequencies, intermediate auricular arteries were more responsive than mesenteric arteries. It is suggested that the intermediate auricular artery of the dog has predominant sensitivity to intraluminally administered tyramine which may be related to the role of this vessel in the regulation of cutaneous blood flow. PMID- 4019529 TI - Neuronal dopamine receptors of the rabbit ear artery: pharmacological characterization of the receptor. AB - Dopamine and apomorphine were examined in the rabbit isolated perfused ear artery for both direct effects on vascular smooth muscle and effects on the response to field stimulation of sympathetic nerve terminals. The neuroinhibitory effect of both dopamine (EC50 = 37 nM) and apomorphine (EC50 = 44 nM) occurred at concentrations which did not produce vasoconstriction. The neuroinhibitory effect of dopamine was shown to be due to inhibition of noradrenaline release by measurement of 3H-overflow from prelabelled tissues. At relatively high concentrations dopamine produced vasoconstriction. In a superfused segment of ear artery, dopamine was found to be a full agonist at the alpha 1-adrenoreceptor, with an EC50 (15 microM) about 75 fold higher than the EC50 for noradrenaline. At concentrations up to 3 microM, apomorphine had no vasoconstrictor activity in the perfused ear artery. Representative examples of several classes of dopamine antagonists, including the phenothiazines, butyrophenones, diphenylbutylpiperidines and benzamides produced competitive antagonism of dopamine or apomorphine-induced inhibition, with nearly identical Kb values against these two agonists. The pharmacological characteristics of the neuronal dopamine receptor on the rabbit ear artery would indicate this receptor to be typical of the D2 subclass, and this tissue to be a useful model for quantitative studies on dopamine receptor agonists and antagonists. PMID- 4019530 TI - Late dislocations in patients with Charnley total hip arthroplasty. AB - I analyzed the cases of thirty-two patients in whom a Charnley total hip arthroplasty had dislocated for the first time between five and ten years postoperatively. I evaluated the possible factors that caused the late dislocations. Most of the factors were similar to those that were also present in a control group of patients who had had an arthroplasty that had not dislocated and in a group in which dislocation had occurred at variable times postoperatively. Two significant factors did emerge. First, the patients with late dislocation had a greater range of motion, especially in flexion, than those in the two control groups. Second, the acetabular component showed radiographic evidence of loosening in more of the patients in the group with late dislocation than in either of the control groups. I postulated, but did not prove, that stretching of the pseudocapsule of the hip over time and extremes of motion may lessen soft-tissue constraints and allow for late dislocation. PMID- 4019531 TI - A combination pelvic osteotomy for acetabular dysplasia in children. AB - Several surgical procedures have been devised to increase acetabular coverage of the femoral head in children with dysplasia of the hip. In this report we describe an acetabuloplasty that combines the key aspects of the Pemberton and Salter osteotomies. It has been used at the Los Angeles Unit of the Shriners Hospital for Crippled Children since the late 1960's. To assess the results of this combination procedure, fifty hips in forty-four children were evaluated at an average of six years postoperatively. The average age at operation was 7.3 years, and 62 per cent of the patients had had prior surgery. Clinically, thirty two hips in which there had been no or slight symptoms preoperatively remained unchanged, twelve that had had preoperative limitations improved, and six showed some deterioration in terms of slight loss of motion, mild pain, and a limp. Roentgenographically, acetabular dysplasia (as measured by the acetabular index and by the center-edge angle of Wiberg) improved in more than 90 per cent of the hips. The roentgenographic results were comparable with those obtained by innominate or pericapsular osteotomy. The combination osteotomy has the advantages of both the Pemberton procedure and the Salter operation and proved to be an excellent surgical procedure for older children whose acetabular development did not progress as well as was expected. PMID- 4019532 TI - Fractures of the lateral humeral condyle in children. AB - I conducted a clinical review of thirty-nine fractures of the lateral condyle of the humerus in children and drew the following conclusions: (1) epiphyseal arrest is rare (it occurred in only one patient, despite malreduction in ten), and (2) fishtail deformity of the distal part of the humerus occurs commonly when malreduction is present. Only two poor results were encountered, both in patients in whom the reduction was grossly inadequate. PMID- 4019533 TI - Internal fixation of fractures and non-unions of the humeral shaft. Indications and results in a multi-center study. AB - We performed ninety-six internal-fixation procedures for fracture or non-union of the humeral shaft in eighty-four patients, with a mean follow-up of 32.6 months (range, three months to fourteen years). The primary indications for operative intervention included humeral shaft fracture in a patient with multiple trauma, non-union, inadequate reduction of a humeral shaft fracture by closed methods, pathological humeral-shaft fracture, and progressive radial-nerve palsy. Methods of internal fixation included compression plates and screws and intramedullary Kuntscher nails or Rush rods. The use of an AO/ASIF compression plate or interfragmentary lag screws with an AO/ASIF neutralization plate in twenty-seven multiply-injured patients resulted in a union rate of 100 per cent and generally good motion of the shoulder and elbow. Five multiply-injured patients also obtained good results through fixation by a modified Hackethal technique using two Rush rods. The use of intramedullary Kuntscher nails resulted in a rate of union of 91 per cent in eleven multiply injured patients. Ten patients with non union of a humeral shaft fracture had an 80 per cent rate of union with the use of an AO/ASIF compression plate. The use of a Kuntscher nail in eleven patients with non-union resulted in a rate of union of only 73 per cent and frequently caused subacromial impingement. Fractures of the humeral shaft that had had an inadequate reduction by closed means or were associated with progressive radial nerve palsy were best managed by a compression plate or the modified Hackethal technique.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4019534 TI - Intraspinal synovial cyst causing sciatica. AB - Four patients who had low-back pain and sciatica were diagnosed as having a lumbar intraspinal extradural synovial cyst adjacent to a facet joint between the fourth and fifth lumbar vertebrae. The patients ranged in age from forty-nine to seventy-one years, and the symptoms and signs involved the fourth or fifth lumbar nerve roots. Roentgenographically, degeneration of the intervertebral discs and facet joints was noted in every patient. Degenerative spondylolisthesis was also a frequent finding. Myelography and computed tomographic scans aided in diagnosis, revealing a soft-tissue lesion, occasionally rimmed with calcification, adjacent to the involved facet joint. The treatment was surgical excision of the cyst, as well as complete laminectomy if there was concomitant spinal stenosis. Follow-up, ranging from eighteen to twenty-five months, revealed complete resolution of the sciatica in all patients. PMID- 4019535 TI - Treatment of trapezius paralysis. AB - Trapezius paralysis is a painful, disabling problem. Eighteen patients with trapezius paralysis were evaluated and initially treated conservatively. Nine patients had had a misdiagnosis prior to evaluation and only one patient was successfully treated conservatively. Ten patients underwent operative reconstruction, consisting of transfer of the levator scapulae and rhomboid muscles. Seven patients were followed for more than two years, and they had five excellent results, one satisfactory result, and one unsatisfactory result. All patients had improved function and correction of deformity, and six patients had good pain relief. PMID- 4019536 TI - Brachial neuritis. AB - Brachial neuritis is an unusual syndrome of unknown etiology that can be confused with other causes of pain or weakness, or both, of the shoulder and arm. It is important to distinguish this disorder because of its dramatic symptoms and relatively good prognosis. Sharp pain, usually in the elbow or shoulder, marks the onset of brachial neuritis, but is relatively short-lived. Weakness generally occurs as the pain is subsiding and most frequently involves the deltoid, spinati, serratus anterior, biceps, and triceps. Paresthesias, atrophy, and sensory loss are inconstant features. Electromyographic findings of fibrillation potentials and positive waves characteristically are found in a pattern indicating combined nerve-root and peripheral nerve involvement. Electromyography more frequently than clinical examination shows that the lesion is bilateral, and also is of both diagnostic and prognostic value. Other laboratory studies serve only to exclude other causes of shoulder pain. The clinical course is variable, but in 90 per cent of patients complete recovery occurs within three years. Recurrences are uncommon. PMID- 4019537 TI - Salvage of replanted parts of the upper extremity. AB - Twelve patients with fifteen replanted parts had vascular exploration in order to salvage the replantation after impending failure developed. Arterial occlusion only was found in eleven parts, while arterial and venous occlusion was found in the other four. Vein grafts were used in ten parts, with success in eight. Thrombectomy was done in six, with success in only one. It was possible to salvage nine of the fifteen replanted parts. The best results were obtained when the revision was done within eleven hours after the replantation. PMID- 4019538 TI - Tarsal and carpal coalition and symphalangism of the Fuhrmann type. Report of a family. AB - We are reporting on fifteen members of a five-generation family (sixty-three members) who had an autosomal dominant osseous disorder that was characterized by tarsal and carpal coalition, symphalangism, short first metacarpals, and abnormalities of the elbow, including humeroradial fusion. This family is similar to the one reported by Fuhrmann et al. PMID- 4019539 TI - Giant-cell tumor of bone with pulmonary metastases. AB - We reviewed the cases of seven patients with histologically benign primary giant cell tumor of bone and histologically proved metastases to the lung. All seven had a Stage-3, aggressive, benign lesion with interruption of the cortex and soft tissue extension. The main histological features of the primary lesion were identical to those of the pulmonary metastases. In only one of the seven patients were the metastases detected simultaneously with the primary lesion. All seven patients were treated by surgical resection of the lung nodules and chemotherapy. Of the seven patients, four were alive and free of disease after an average follow-up of nine years; two were receiving chemotherapy; and one, who had had immunosuppression for an allograft transplant, died less than one year after the discovery of the pulmonary lesions. Based on this small series, we concluded that patients with a Stage-3 giant-cell tumor of bone may be at risk for pulmonary spread of the disease. This lesion, with its benign histological picture even in lung lesions, has a favorable prognosis when treated with pulmonary resection of the nodules. However, the role for chemotherapy after pulmonary surgery is still unclear. PMID- 4019540 TI - Rib perichondrial grafts for the repair of full-thickness articular-cartilage defects. A morphological and biochemical study in rabbits. AB - The purpose of this study was to investigate the use of perichondrial grafts in articular cartilage defects and to characterize the newly formed cartilage. In a rabbit model, rib perichondrium was used to repair full-thickness defects in the femoral condyle. The quality of repair was then evaluated histologically and biochemically at six and twelve weeks after grafting. Unacceptable results were obtained in 50 per cent of the rabbits. These failures were due to condylar fracture in 20 per cent, failure of graft attachment in 20 per cent, and infection in 10 per cent. The technique of grafting must be improved to increase the percentage of successful grafts in which neocartilage with a relatively normal chemical composition fills the articular cartilage defect. Successful grafts proliferate to fill the full-thickness defect with neocartilage, which has biochemical characteristics that are similar to those of hyaline cartilage. PMID- 4019541 TI - Cephalosporins for prophylaxis in operative repair of femoral fractures. Levels in serum, muscle, and hematoma. AB - We conducted a prospective controlled study of thirty patients who had an open reduction with internal fixation of a closed fracture of the femur. Each patient received cefamandole, cefazolin, or cefoxitin intravenously (twenty-five milligrams per kilogram of body weight) on entry into the operating room. Intraoperatively, samples of blood, muscle, and organizing hematoma were collected for determination of levels of the antimicrobial agent. Throughout the operation, cefazolin was shown to result in significantly higher levels in serum. The mean concentrations in muscle were similar for all three drugs, but the levels in the hematoma were twice as high with cefazolin as with cefamandole or cefoxitin. No correlation was evident between the concentration of any of these antibiotics in the hematoma and the interval between injury and operation. PMID- 4019542 TI - The clinicopathological spectrum of non-tuberculous mycobacterial osteoarticular infections. AB - We studied the clinicopathological features of eight patients in whom a non tuberculous mycobacterium was unexpectedly isolated from osteoarticular material obtained at operation. Three distinct types of infection with non-tuberculous mycobacteria were found: tenosynovitis, synovitis, and osteomyelitis. Tissue specimens from these sites showed a spectrum of pathological findings, including (1) virtually no inflammation, (2) mild to severe non-specific chronic inflammation, (3) granulomas without necrosis, and (4) caseating epithelioid granulomas that were indistinguishable from those of tuberculosis. In six patients the infection responded well to adequate surgical excision alone. In the remaining two the infection responded to surgical intervention and antituberculous therapy. PMID- 4019544 TI - Femoral fracture following hip arthroplasty. Brief note on treatment. PMID- 4019543 TI - Reconstruction of the lateral ligaments of the ankle using the plantaris tendon. AB - The plantaris tendon was used to reconstruct the torn lateral ligaments in the ankles of nine patients in whom surgical repair of the ligaments was not feasible. All of these patients were followed for more than two years and were able to return to their preoperative occupational and athletic activities. The use of the plantaris tendon permits an anatomical reconstruction of the lateral ligaments and, unlike previously described procedures, avoids sacrificing the dynamic effect of the peroneus brevis muscle in preventing inversion of the foot. PMID- 4019545 TI - Acute traumatic bowing of the tibia without fracture. Case report. PMID- 4019546 TI - Florid reactive periostitis of the proximal phalanx. Case report. PMID- 4019547 TI - Spontaneous regression of osteochondromas. Two case reports. PMID- 4019548 TI - Rotator cuff disease of the shoulder. PMID- 4019549 TI - The importance of proximal and distal air bronchograms in the management of atelectasis. AB - Correlation of chest radiographic appearances with concurrent fibreoptic bronchoscopy in patients observed while in intensive care, and with lobar or multilobar atelectasis due to retained secretions, suggests that three levels of air bronchogram can be identified: Proximal: air is visible only to the level of the main bronchus, bronchus intermedius or lobar bronchi. Intermediate: air is visible down to the segmental bronchi. Distal: air is visible down to the subsegmental bronchi or beyond. Proximal or intermediate air bronchograms signify accumulation of secretions in central bronchi and indicate the need for fibreoptic bronchoscopy to aspirate secretions: a distal air bronchogram signifies peripheral bronchial obstruction thus precluding effective fibreoptic bronchoscopy; chest physiotherapy is then a more appropriate treatment. The proximal air bronchogram may change in extent or definition-sometimes rapidly; a receding or an increasingly poorly defined proximal air bronchogram are danger signals of centrally accumulating secretions which may lead to respiratory arrest. PMID- 4019550 TI - Asymmetrical changes in asbestos-related disease. AB - The radiographic changes in 200 patients with known or suspected asbestos exposure were reviewed. Pleural plaques or thickening, with or without calcification, occurred solely or predominantly on the left side in 90, on the right side in 32, and equally bilaterally in 44. Asymmetry is common in asbestos related disease, and apparently unilateral findings should prompt a search for more subtle changes elsewhere. PMID- 4019552 TI - Salpingitis isthmica nodosa in female infertility. AB - A retrospective study was undertaken to evaluate the radiologic appearance of salpingitis isthmica nodosa (SIN) in the fallopian tubes of 150 consecutive patients having hysterosalpingograms performed almost exclusively for primary and secondary infertility. SIN was observed in 13 of these 150 patients. The characteristic radiologic features of this condition are minute loculations of contrast medium adjacent to the tubal lumen which range in size up to 2 mm in diameter and are clustered together over a tubal length of 1 to 2 cm. Although the most frequent site of occurrence is in the proximal isthmic portion of the tube, there is occasional involvement of the distal isthmus and even the interstitial portion of the adjacent uterine cornu. Associated tubal abnormalities in this condition such as hydrosalpinx and tubal occlusion help explain the increased incidence of tubal pregnancy and infertility in patients with SIN. PMID- 4019551 TI - Iohexol: a new, nonionic agent in adult peripheral arteriography. AB - The safety and efficacy of iohexol, a new nonionic contrast agent, were compared with a diatrizoate (Renografin-76) in a double-blind, parallel study of peripheral arteriography by femoral puncture in 60 patients. Extra-large field serial peripheral arteriography was used and a posterior tibial nerve block was applied to all patients in the study. Similar changes in blood chemistry were observed following the injection of iohexol and diatrizoate but these changes did not require corrective measures. Significantly more patients complained of a sensation of severe heat after receiving diatrizoate (38%) than after the injection of iohexol (10%) (p = 0.001). Four patients in the diatrizoate group experienced one or more adverse reactions, including mild urticaria. Only mild nausea was reported by a single patient in the iohexol group. Overall, 100% of the studies were diagnostic but more of the radiographs taken after the injection of iohexol were rated excellent than after the injection of diatrizoate. PMID- 4019554 TI - The cooling effect of tubular liquid flow during radiofrequency heating: the "rind" survival hypothesis. AB - The influence of flowing blood on temperatures reached in nearby tumor cells during localized radiofrequency (RF) hyperthermia may be critical for tumor cell survival. We have investigated the effect on the temperatures nearby of blood flowing in a vessel. Using 13.56 MHz capacitive RF, we heated gel phantoms containing a tube through which cooling solution could flow. Our results demonstrated a reduction in temperature of the order of 3 degrees C around the tube when coolant was flowing, and the cooling pattern correlated with theoretical mathematical predictions. Up to 564 joules per minute could be removed from the system. Our results suggest the improbability of uniform tumor cell killing by RF heating. A scheme for integrating the concepts of physical cell damage, biochemical cell damage and peripheral cell survival in a tumor nodule is presented. PMID- 4019553 TI - The radiologic assessment of iatrogenic urethral injury. AB - Iatrogenic urethral injury producing urethral stricture results from urethral instrumentation, bladder catheterisation and, rarely, as a result of abdomino perineal resection for carcinoma of the rectum. We here record our experience with iatrogenic urethral strictures and correlate the site of urethral stricture with its etiology. Because our hospital is a referral centre for urethral disease our results indicate that iatrogenic urethral injury (40%) is more common than previously described. They also indicate that urethral stricture due to instrumentation is more common in the bulbomembranous urethra (approximately 80%) and that stricture due to catheterisation is more common at the penoscrotal junction (approximately 70%). Instrument strictures are usually short and well defined. Catheter strictures are generally long and irregular, commonly being associated with visualisation of the glands of Littre. PMID- 4019555 TI - Hodgkin's disease complicating pregnancy. AB - We report our experience in the management of 12 patients with Hodgkin's disease associated with pregnancy. Three patients presented in the first trimester; pregnancy was interrupted in two. They are alive and well after 8, 14 and 16 years of follow-up. Two patients presented in the second trimester; they elected to continue their pregnancies and both died from progressive disease, one of them having refused therapy. The remaining seven patients in the third trimester continued pregnancy; they are all alive after five to 11 years of follow-up and one is alive with active disease. Two patients received radiotherapy during pregnancy. Both had normal outcomes of pregnancy and no fetal abnormalities were found. There is no evidence to suggest that either pregnancy affects the course of Hodgkin's disease or that Hodgkin's disease affects pregnancy. General rules as to how to proceed in patients with Hodgkin's disease complicated by pregnancy are described. PMID- 4019556 TI - Preliminary report: acetylsalicylic acid therapy in the treatment of complications following abdominal radiation. AB - A group of 10 patients with complications following pelvic irradiation were treated with acetylsalicylic acid (ASA). Epithelial ulceration was healed in four of six patients and improved in one. Radiation enteritis was decreased or abolished in all patients who remained on ASA. PMID- 4019557 TI - Estimation of patient age based on plain chest radiographs. AB - Patient age is an essential part of a clinical history, but it is not always provided by referring physicians. We assessed the ability of four radiologists with different levels of expertise (first-year resident to professor emeritus) to predict patient age based on postero-anterior and lateral chest radiographs from 171 patients. All four were able to predict age with a mean error of less than 15 years, but there were statistically significant differences among them. Surprisingly, observer experience did not correlate with accuracy of patient age estimation. While many factors probably operate, the estimation of patient age relies heavily on "gestalt." PMID- 4019558 TI - Pitfalls to avoid: the right paraspinal pseudotumor. AB - Fat in the fissure for the ligamentum teres, if abundant and sagittally oriented, will outline the right margin of the lateral segment of the left lobe of liver. This produces the appearance of a right paraspinal mass on plain abdominal radiographs. The nature of the anatomical relationships has been demonstrated using computed tomography. PMID- 4019559 TI - Aluminum hydroxide gel bezoar--CT diagnosis. AB - An obstructing aluminum hydroxide gel bezoar was first recognized on a retrograde gastrografin study through an ileostomy. In retrospect, a computed tomographic (CT) scan had demonstrated the bezoar as a high density intraluminal mass surrounded by somewhat less dense contrast material distending the bowel. A CT image of a phantom made of aluminum hydroxide gel surrounded by gastrografin was remarkably similar. PMID- 4019560 TI - Rapid regional osteolysis from pancreatic carcinoma. PMID- 4019561 TI - [Superior venacavography at the patient's bedside]. AB - Acute onset of superior vena cava syndrome in critically ill patients, hours after cardiac surgery, needs angiographic documentation without delay in order to proceed with appropriate treatment. Bedside diagnostic venacavography was done for two patients in the surgical intensive care unit with a simple and safe method using a central venous catheter already in place. PMID- 4019562 TI - Congenital left superior vena cava with absent right superior vena cava: a cause of progressive mediastinal widening. AB - We wish to report a patient with the rare anomaly of congenital left superior vena cava and absent right superior vena cava. This became apparent on chest radiographs by the development of a left mediastinal "mass" over a one-year period. The role of contrast-enhanced computed tomographic scanning in the detection of venous anomalies is stressed. PMID- 4019563 TI - Azygous continuation of a left inferior vena cava with a retroaortic right renal vein. AB - Anomalies of the inferior vena cava, azygous venous system and renal veins may take many forms. We report a patient with azygous continuation of a left-sided inferior vena cava with an associated retroaortic right renal vein. To our knowledge, this is the first such report. PMID- 4019564 TI - Resolution of myositis ossificans in a hemophiliac. AB - Hemophilic myositis ossificans at the site of previous hemorrhage is a well recognised entity. A phenomenon, not previously described, is gradual absorption of a well corticated heterotopic bone over a period of five-and-a-half years. We here report this happening in a patient. PMID- 4019565 TI - Acute bilobar collapse secondary to endobronchial metastatic seminoma. AB - We report here a patient with tracheal and endobronchial metastatic seminoma who presented with acute respiratory failure with right upper and middle lobe collapse. Diagnosis of the etiology of the atelectasis was made by fiberoptic bronchoscopy. Radiation therapy caused a marked reversal of the atelectasis. PMID- 4019566 TI - Growth dependent cell proliferation kinetics of a human malignant melanoma grown in nude mice. AB - A human malignant melanoma was grown in nude mice. The tumour showed an exponential growth for several weeks which gradually slowed down, until following week 8 the tumour growth ceased. The reasons for this growth pattern were examined by labelling techniques (PLM, LI). The tumour cell production as quantified by the growth fraction, showed only a moderate reduction which, taken alone, could not explain the growth cessation. The important mechanism seems to be an increased loss of tumour cells during the intermitotic interval. While the loss of cells/h remains constant the total intermitotic cell loss is increased because the cell cycle times are prolonged by 50% from the exponential phase (45 h in week 3) to the plateau phase (66 h in week 8). PMID- 4019568 TI - Establishment of a human carcinoembryonic antigen (CEA)-producing cell line in a protein-free chemically defined medium. AB - To examine whether a human carcinoembryonic antigen (CEA)-producing cell can proliferate and sythesize CEA in vitro in culture without protein supplements, long-term cultivation of such cells was carried out in a protein-free chemically defined medium. Using stepwise decreases in fetal bovine serum concentration, continuous growth of the cells was established in a protein-free am's F-12 medium. The cells, designated as HLC-Yl, have been propagated in this medium for 3 years. The population doubling time of the cells is about 52 h. Addition of the serum stimulated the cell growth (population doubling time = 27 h). Saturation density was not increased by the addition of serum. The cells grown in a protein free F-12 secrete large amounts of CEA (65.4 +/- 2.6 ng/10(6) cells/24 h). Addition of serum did not stimulate the production of CEA. The cells produced tumours when inoculated into athymic nude mice. The mice bearing the tumour showed high serum CEA levels, and CEA was demonstrated in the tumour tissue by the immunoperoxidase method. The present study suggests that cells grown in a protein-free medium do not require serum components for their growth or CEA synthesis and provide an excellent model for better understanding the growth and production of CEA in human lung cancer cells. PMID- 4019567 TI - Nitrogen mustard interference with potassium transport systems in Ehrlich ascites tumor cells. AB - Nitrogen mustard (N-mustard) inhibits the ouabain-sensitive and the furosemide sensitive Rb uptake of Ehrlich ascites tumor cells, whereas the transport, which is resistant to both inhibitors, is not affected by the alkylating agent. At N mustard concentrations below 10 microM, the reduction in Rb uptake is predominantly due to an interference with the furosemide-sensitive system. The dose response curve for the inhibition by N-mustard of the furosemide-sensitive Rb uptake closely parallels the dose response curve for the anti-tumor activity of the alkylating drug. This is in contrast to the behaviour of the ouabain sensitive Rb transport. The inhibition of the furosemide-sensitive Rb uptake is expressed much less in cells which are resistant to N-mustard. The recovery of the furosemide-sensitive transport system after a single exposure to N-mustard is relatively slow and characterized by an initial 4 h lag period, whereas the repair of DNA-interstrand cross-links starts immediately after removal of the drug. At mM concentrations furosemide blocks the multiplication of Ehrlich ascites tumor cells. However, lower concentrations of furosemide which cause a 50% reduction in the furosemide-sensitive Rb uptake do not interfere with cell proliferation. This is in contrast to the behaviour of N-mustard which exerts a clear-cut depression of cell growth at concentrations leading to a 50% inhibition of the furosemide-sensitive Rb transport. It is concluded, therefore, that the inhibition of the furosemide-sensitive system alone is not sufficient to explain the anti-tumor activity of the alkylating agent. The effect is discussed as part of a more extended N-mustard-induced membrane alteration which may be important for the growth inhibitory effect of the alkylating agent. PMID- 4019569 TI - Effect of oral cholestyramine on the elimination of high-dose methotrexate. AB - The anion exchange resin cholestyramine binds methotrexate (MTX) effectively in vitro. The binding capacity exceeds that of activated charcoal by a factor of 5.4. On two patients undergoing high-dose MTX therapy it is also shown that cholestyramine binds MTX in vivo. This leads to an enhanced non-renal excretion of MTX. Therefore, cholestyramine may be of clinical value in patients who develop renal function impairment whilst undergoing MTX therapy. PMID- 4019570 TI - Cloning ovarian carcinoma cells in an agar double layer versus a methylcellulose monolayer system. A comparison of two methods. AB - Human ovarian cancer cells from ten patients were cultured in the agar double layer assay as described by Hamburger and Salmon and in a methylcellulose monolayer system. The assays were compared under the same experimental conditions. The rate of positives (defined as greater than 30 colonies/dish) was 75% in the methylcellulose assay and 69% in the agar double layer. Plating efficiency ranged in the methylcellulose assay between 0.021% and 0.089% and in the agar double layer from 0.015% to 0.094%. Cytological and cytochemical staining of cells obtained from colonies in both test systems and of the tumour cells prior to plating revealed the same morphology. The methylcellulose monolayer system requires less additives than necessary in the agar double layer system. Furthermore, it is easier to handle with respect to the plating procedure and less time consuming. In addition, the effect of the anti-oestrogen tamoxifen on colony formation was tested. The dose response curves for colony formation with tamoxifen proved to be identical in both systems. At a concentration of 10( 6) M an inhibition of colony formation of more than 70% of controls was observed in the agar and in the methylcellulose system. PMID- 4019571 TI - Failure of mitomycin-vindesine combination chemotherapy as salvage treatment for metastatic breast cancer. AB - Mitomycin plus vindesine have been utilized as salvage therapy in metastatic breast cancer patients refractory to first line chemotherapy. No response was observed in 15 consecutively evaluable patients; according to the Gehan test a lack of effectiveness of this regimen is suggested at least in heavily pretreated patients. PMID- 4019572 TI - Seasonal variations in the frequency distribution of breast cancer in Greek women according to the month of their birth. AB - The frequency distribution of patients with breast cancer according to the month of their birth was examined in 1,165 women comprising the total number of patients recorded in our cancer registry from 1975 until the end of 1982. Statistical evaluation of this material using an exact chi 2 for simple null hypothesis demonstrated the existence of two high frequency peaks corresponding to March and April in the spring and September in the autumn. These frequencies were significantly higher (P less than 0.001) than those of the remaining months. Confirmation of this finding would imply the introduction of a new variant in breast cancer epidemiology. PMID- 4019573 TI - Coincidence of infectious osteomyelitis and disseminated neuroblastoma: a diagnostic dilemma solved by scintigraphic imaging. AB - The case of a 41/2-year-old girl with disseminated neuroblastoma and concomitant osteomyelitis is reported. Neuroblastoma was detected in the vertebral column, the right suprarenal fossa, the left side of cranium and in bone marrow aspirates. Osteomyelitis was present in the left femur and was due to Salmonella tennessee. For the first time in the literature the two lesions were demonstrated by means of simultaneous 131I-MIBG and 99mTc-DPD scintigraphy. The diagnoses were proved by direct histological and microbiological studies. PMID- 4019574 TI - Five year experience with axillopopliteal bypasses for limb salvage. AB - Over the last 5 years, we have performed 34 axillopopliteal bypasses to salvage threatened limbs of patients in whom standard anatomic or extra-anatomic bypasses had either failed or were not feasible. The indications for these axillopopliteal bypasses, all of which were performed with 6 mm polytetrafluoroethylene grafts, were: (1) severe atherosclerotic disease of the common, superficial and deep femoral arteries which precluded use of these vessels for inflow or outflow for a standard vascular procedure (15 cases); (2) failed aortofemoral bypass with sufficient fibrosis or disease progression in the profunda femoris artery to prevent its use in a reoperation (7 cases); (3) insufficient hemodynamic improvement and failure to heal a foot lesion after an axillofemoral bypass (9 cases); and (4) sepsis in the groin from a previously infected bypass (3 cases). Graft patency was determined by objective measures. Cumulative life table graft patency rates were 77% at 1 year, 51% at 3 years, and 45% at 5 years. Although these rates are not as good as those for our axillofemoral bypasses (75% at 5 years), 22 limbs revascularized by axillopopliteal bypasses were salvaged with function for 1 year and 9 were salvaged with function for 2 years or longer in situations in which no option other than amputation was available. This justifies the continuing use of axillopopliteal bypass in an effort to salvage those limbs imminently threatened with amputation and in which no standard reconstruction is feasible because of disease or infection. PMID- 4019575 TI - Clinical contact with the trauma patient enhances accuracy of chest roentgenogram interpretation in predicting traumatic rupture of the aorta. AB - In a previous retrospective clinical study, we reported that clinicians having contact with the trauma patient interpreted widened mediastinum (WMED) in association with TRA with greater accuracy than did staff radiologists reviewing the same chest films (0.96 vs 0.83), while staff radiologists interpreted WMED with far greater frequency than did their clinical counterparts (0.40 vs. 0.27, p = 0.01). These findings may be related to differences in chest film interpretation or to the influence of clinical contact with the patient. To answer this question, data from a study in which a group of four surgeons and two radiologists was asked individually and in a blinded fashion to interpret, without the clinical history, the chest x-rays of 149 trauma patients who had undergone aortography to rule out TRA were examined by specialty affiliation. Sixteen of the patients had TRA. Surgeons interpreted WMED with the same frequency as radiologists (0.47 vs 0.54) and with far greater frequency (0.47 vs 0.27, p = 0.06) and poorer accuracy (0.61 vs 0.96) than they did in the previous clinical review. No significant differences were detected between surgeons and radiologists in the overall rate of interpretation of WMED, in the prediction of aortic rupture, or in the ordering of aortography based purely upon chest film interpretation. We conclude that trauma surgeons and radiologists, isolated from the patient interpret the chest film signs associated with TRA similarly. Clinical contact with the trauma patient may modify what is seen on chest film in a way that contributes to greater accuracy in the diagnosis of TRA. Radiographic criteria for ordering aortography are thus best used in conjunction with careful clinical evaluation of the patient. PMID- 4019576 TI - Initial Canadian experience with artificial blood (Fluosol-DA-20%) in severely anemic patients. AB - Fluosol-DA-20% (FDA), a synthetic perfluorocarbon emulsion with oxygen (O2) carrying capability, has recently become available in North America for clinical trials in severely anemic patients. Three patients have so far received FDA at our institution. All were severely anemic (Hct's 12-15%), and were administered FDA in anticipation of perioperative blood loss. Observations made in these patients indicate that: FDA can act as a plasma expander; no firm conclusions can be made as to whether FDA increases O2 consumption in the absence of directly measured arterial and mixed-venous O2 contents; mixed-venous oxyhemoglobin saturation at high FiO2 increases following FDA administration because a significant proportion of the consumed O2 (24-37% in our patients at FiO2 = 1.0) is transported by FDA; hemodynamic reactions to a test dose of FDA may occur, and may be serious enough to preclude further FDA administration; and technical recommendations for the administration of FDA should include the use of direct arterial and mixed-venous O2-content determinations, and continuous spectrophotometric mixed-venous oxyhemoglobin saturation monitoring. PMID- 4019577 TI - Successful one stage repair of coarctation of the aorta and aneurysm of the ascending aorta in a child. AB - A case of successful one stage repair of aortic coarctation and ascending aortic aneurysm in a 10 year old boy with cystic medial necrosis and congenital bicuspid aortic valve is presented. The patient underwent correction of both lesions at the same operation through two separate incisions. The coarctation was repaired first. The aortic valve was found to be hemodynamically normal and was not replaced. The patient leads a normal life at five and half years after operation and is playing ice hockey with no limitations. Close and long-term follow-up is considered essential in view of the potential complications. PMID- 4019578 TI - XXXIII Congress of the European Society for Cardiovascular Surgery. Madrid, Spain, September 6-7-8, 1984. Abstracts. PMID- 4019579 TI - A transient rise in cytosolic calcium follows stimulation of quiescent cells with growth factors and is inhibitable with phorbol myristate acetate. AB - We have used aequorin as an indicator for the intracellular free calcium ion concentration [( Ca++]i) of Swiss 3T3 fibroblasts. Estimated [Ca++]i of serum deprived, subconfluent fibroblasts was 89 (+/-20) nM, almost twofold higher than that of subconfluent cells growing in serum, whose [Ca++]i was 50 (+/-19) nM. Serum, partially purified platelet-derived growth factor (PDGF), and fibroblast growth factor (FGF) stimulated DNA synthesis by the serum-deprived cells, whereas epidermal growth factor (EGF) did not. Serum immediately and transiently elevated the [Ca++]i of serum-deprived cells, which reached a maximal value of 5.3 microM at 18 s poststimulation but returned to near prestimulatory levels within 3 min. Moreover, no further changes in [Ca++]i were observed during 12 subsequent h of continuous recording. PDGF produced a peak rise in [Ca++]i to approximately 1.4 microM at 115 s after stimulation, and FGF to approximately 1.2 microM at 135 s after stimulation. EGF caused no change in [Ca++]i. The primary source of calcium for these transients was intracellular, since the magnitude of the serum-induced rise in [Ca++]i was reduced by only 30% in the absence of exogenous calcium. Phorbol 12-myristate 13-acetate (PMA) had no effect on resting [Ca++]i. When, however, quiescent cells were treated for 30 min with 100 nM PMA, serum-induced rises in [Ca++]i were reduced by sevenfold. PMA did not inhibit growth factor induced DNA synthesis and was by itself partially mitogenic. We suggest that if calcium is involved as a cytoplasmic signal for mitogenic activation of quiescent fibroblasts, its action is early, transient, and can be partially substituted for by PMA. Activated protein kinase C may regulate growth factor-induced increases in [Ca++]i. PMID- 4019580 TI - Conversion of embryonic form to adult forms of N-CAM in vitro: results from de novo synthesis of adult forms. AB - During normal development, the neural cell adhesion molecule N-CAM changes at the cell-surface from a sialic acid-rich embryonic, or E form, to several adult, or A forms that have less sialic acid (E-to-A conversion). To investigate the cellular and molecular mechanisms that underlie these changes, we have established conditions under which E-to-A conversion occurs in cultured explants of central nervous system tissues. Mouse cerebellum, chick spinal cord, and chick retina that express the E form of N-CAM were dissected and cultured on collagen gels. After 3-6 d in culture, increased proportions of A forms were synthesized, as revealed by specific immunoprecipitation and immunoblotting. The rate of E-to-A conversion and the proportions of the different A forms synthesized in vitro were similar to those observed for the tissues in vivo at comparable times. In addition, the explants incorporated radioactive precursors of amino sugars into N CAM, and the electrophoretic mobilities of the E and A forms of N-CAM were altered by treatment with neuraminidase in a way comparable to that found for N CAM obtained directly from tissue. These results suggest that the post translational processing in vitro was similar to that in vivo. Logistic studies on cell division and death in the explants suggested that E-to-A conversion resulted mainly from a specific increase in synthesis of A forms in individual cells rather than as a consequence of differential birth or death within distinct cell populations. The data were consistent with the possibility that the increase in synthesis of A forms occurred either in cells that had previously synthesized E forms or in a distinct population of cells that already synthesized A forms. Cells dissociated from embryonic central nervous system tissues and cultured in vitro were also found to undergo E-to-A conversion at the same rate as the explant cultures, which suggests that if intercellular signals were responsible for initiation of the change in synthetic pattern, they had already occurred in vivo before the time of culture. In pulse-chase experiments, the E form of N-CAM that was synthesized during the first day after explantation persisted as E form for several days, at times when newly synthesized N-CAM was predominantly in A forms. These results indicate that in cultured neural tissue, the E form of N-CAM is not processed into A forms but is gradually degraded and replaced by newly synthesized A forms.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 4019581 TI - Synthesis of cytoskeletal and contractile proteins by cultured IMR-90 fibroblasts. AB - Models of the assembly of cytoskeletal and contractile proteins of eukaryotic cells require quantitative information about the rates of synthesis of individual component proteins. We applied the dual isotope technique of Clark and Zak (1981, J. Biol. Chem., 256:4863-4870) to measure the synthesis rates of cytoskeletal and contractile proteins in stationary and growing cultures of IMR-90 fibroblasts. Fibroblast proteins were labeled to equilibrium with [14C]leucine over several days, at the end of which there was a 4-h pulse with [3H]leucine. Fractional synthesis rates (percent per hour) were calculated from the 3H/14C ratio of cell protein extracts or protein purified by one- or two-dimensional polyacrylamide gel electrophoresis and the 3H/14C ratio of medium-free leucine. The average fractional synthesis rate for total, SDS- or urea-soluble; Triton-soluble; and cytoskeletal protein extracts in stationary cells each was approximately 4.0%/h. The range of values for the synthesis of individual proteins from total cell extracts or cytoskeletal extracts sliced from one-dimensional gels was similar, though this range was greater than that for major proteins of Triton-soluble protein extracts. Three specific cytoskeletal proteins--actin, vimentin, and tubulin--were synthesized at similar rates that were significantly slower than the average fractional synthesis rate for total protein. Myosin, on the other hand, was synthesized faster than average. Synthesis rates were the same for beta and gamma-actin and polymerized (cytoskeletal extract) vs. Triton-soluble actin. The same was true for alpha- and beta-tubulin and two different forms of vimentin. Synthesis rates were uniformly higher in growing cells, though the same pattern of differential rates was observed as for stationary cells. Synthesis rates in growing cells were higher than the rate necessary to maintain the growth rate, even for those cytoskeletal proteins being synthesized slowly. Therefore, there appears to be some turnover of these cytoskeletal elements even during growth. We conclude that proteins in cytoskeletal extracts may have nonuniform rates of synthesis, but at least one important subclass of cytoskeletal proteins that comprise filament subunits have the same synthesis rates. PMID- 4019582 TI - Abrogation of cell surface expression of human class I transplantation antigens by an adenovirus protein in Xenopus laevis oocytes. AB - Class I transplantation antigens form complexes with a virus protein encoded in the early region E3 of the adenovirus-2 genome. The interaction between this viral glycoprotein, E19, and nascent human class I antigens has been examined by microinjecting purified mRNA into Xenopus laevis oocytes. Both E19 and the two class I antigen subunits, the heavy chain and beta 2-microglobulin (beta 2M), were efficiently translated. The heavy chains did not become terminally glycosylated, as monitored by endoglycosidase H digestion, and were not expressed on the oocyte surface unless they were associated with beta 2M. The E19 protein did not become terminally glycosylated, and we failed to detect this viral protein on the surface of the oocytes. Co-translation of heavy chain and E19 mRNA demonstrated that the two proteins associate intracellularly. However, neither protein appeared to be transported to the trans-Golgi compartment. Similar observations were made in adenovirus-infected HeLa cells. Heavy chains bound to beta 2M became terminally glycosylated in oocytes in the presence of low concentrations of E19. At high concentrations of the viral protein, no carbohydrate modifications and no cell surface expression of class I antigens were apparent. Thus, beta 2M and E19 have opposite effects on the intracellular transport of the heavy chains. These data suggest that adenovirus-2 may impede the cell surface expression of class I antigens to escape immune surveillance. PMID- 4019583 TI - Efficient cytoplasmic delivery of a fluorescent dye by pH-sensitive immunoliposomes. AB - We previously showed that liposomes composed of dioleoylphosphatidyl-ethanolamine and palmitoyl-homocysteine (8:2) are highly fusion competent when exposed to an acidic environment of pH less than 6.5. (Connor, J., M. B. Yatvin, and L. Huang, 1984, Proc. Natl. Acad. Sci. USA. 81:1715-1718). Palmitoyl anti-H2Kk was incorporated into these pH-sensitive liposomes by a modified reserve-phase evaporation method. Mouse L929 cells (k haplotype) treated with immunoliposomes composed of dioleoylphosphatidylethanolamine/palmitoyl-homocysteine (8:2) with an entrapped fluorescent dye, calcein, showed diffused fluorescence throughout the cytoplasm. Measurements by use of a microscope-associated photometer gave an approximate value of 50 microM for the cytoplasmic calcein concentration. This concentration represents an efficient delivery of the aqueous content of the immunoliposome. Cells treated with immunoliposomes composed of dioleoylphosphatidylcholine (pH-insensitive liposomes) showed only punctate fluorescence. The cytoplasmic delivery of calcein by the pH-sensitive immunoliposomes could be inhibited by chloroquine or by incubation at 20 degrees C. These results suggest that the efficient cytoplasmic delivery involves the endocytic pathway, particularly the acidic organelles such as the endosomes and/or lysosomes. One possibility is that the immunoliposomes fuse with the endosome membranes from within the endosomes, thus releasing the contents into the cytoplasm. This nontoxic method should be widely applicable to the intracellular delivery of biomolecules into living cells. PMID- 4019584 TI - Hereditary pituitary dwarfism in mice affects skeletal and cardiac myosin isozyme transitions differently. AB - The dwarf mutation in mice interferes with the development of those anterior pituitary cells responsible for production of thyroid stimulating hormone, growth hormone, and prolactin. Myosin isozyme transitions in both cardiac and skeletal muscle were also found to be affected in this mutant. Electrophoresis of native myosins demonstrated that the fetal (V3) to adult (V1) ventricular cardiac isozyme transition was completely blocked in dwarf mice; in contrast, the neonatal to adult fast myosin transition in hind limb skeletal muscle was slowed but not totally inhibited. The persistence of neonatal myosin heavy chain for up to 55-75 d after birth in dwarf mice, as compared with 16 d in normal mice, was directly demonstrated by polypeptide and immunopolypeptide mapping. Morphological examination of 18-36-d-old dwarf skeletal muscles by optical and electron microscopy revealed a relative immaturity, but no signs of gross pathology were evident. Immunocytochemical analysis showed that the abnormal persistence of neonatal myosin occurs in most of the fibers. Multiple injections of thyroxine restored a normal isozyme complement to both cardiac and skeletal muscles within 11-15 d. Therefore, the effects of the dwarf mutation on myosin isozymes can be explained by the lack of thyroid hormone in these animals. Because the synthesis of growth hormone is not stimulated by thyroid hormone in dwarf mice as it would be in normal animals, these results demonstrate that thyroid hormone promotes myosin isozyme transitions independent of growth hormone production. PMID- 4019585 TI - Alterations in neural crest migration by a monoclonal antibody that affects cell adhesion. AB - The possible role of a 140-kD cell surface complex in neural crest adhesion and migration was examined using a monoclonal antibody JG22, first described by Greve and Gottlieb (1982, J. Cell. Biochem. 18:221-229). The addition of JG22 to neural crest cells in vitro caused a rapid change in morphology of cells plated on either fibronectin or laminin substrates. The cells became round and phase bright, often detaching from the dish or forming aggregates of rounded cells. Other tissues such as somites, notochords, and neural tubes were unaffected by the antibody in vitro even though the JG22 antigen is detectable in embryonic tissue sections on the surface of the myotome, neural tube, and notochord. The effects of the JG22 on neural crest migration in vivo were examined by a new perturbation approach in which both the antibody and the hybridoma cells were microinjected onto neural crest pathways. Hybridoma cells were labeled with a fluorescent cell marker that is nondeleterious and that is preserved after fixation and tissue sectioning. The JG22 antibody and hybridoma cells caused a marked reduction in cranial neural crest migration, a build-up of neural crest cells within the lumen of the neural tube, and some migration along aberrant pathways. Neural crest migration in the trunk was affected to a much lesser extent. In both cranial and trunk regions, a cell free zone of one or more cell diameters was generally observed between neural crest cells and the JG22 hybridoma cells. Two other monoclonal antibodies, 1-B and 1-N, were used as controls. Both 1-B and 1-N bind to bands of the 140-kD complex precipitated by JG22. Neither control antibody affected neural crest adhesion in vitro or neural crest migration in situ. This suggests that the observed alterations in neural crest migration are due to a functional block of the 140-kD complex. PMID- 4019586 TI - Interaction of lectins with membrane receptors on erythrocyte surfaces. AB - The interactions of human genotype AO erythrocytes (red blood cells) (RBCs) with N-acetylgalactosamine-reactive lectins isolated from Helix pomatia (HPA) and from Dolichos biflorus (DBA) were studied. Binding curves obtained with the use of tritium-labeled lectins showed that the maximal numbers of lectin molecules capable of binding to human genotype AO RBCs were 3.8 X 10(5) and 2.7 X 10(5) molecules/RBC for HPA and DBA, respectively. The binding of one type of lectin may influence the binding of another type. HPA was found to inhibit the binding of DBA, but not vice versa. The binding of HPA was weakly inhibited by a beta-D galactose-reactive lectin isolated from Ricinus communis (designated RCA1). Limulus polyphemus lectin (LPA), with specificity for N-acetylneuraminic acid, did not influence the binding of HPA but enhanced the binding of DBA. About 80% of LPA receptors (N-acetylneuraminic acid) were removed from RBC surfaces by neuraminidase treatment. Neuraminidase treatment of RBCs resulted in increases of binding of both HPA and DBA, but through different mechanisms. An equal number (7.6 X 10(5) of new HPA sites were generated on genotypes AO and OO RBCs by neuraminidase treatment, and these new sites accounted for the enhancement (AO cells) and appearance (OO cells) of hemagglutinability by HPA. Neuraminidase treatment did not generate new DBA sites, but increased the DBA affinity for the existing receptors; as a result, genotype AO cells increased their hemagglutinability by DBA, while OO cells remained unagglutinable. The use of RBCs of different genotypes in binding assays with 3H-labeled lectins of known specificities provides an experimental system for studying cell-cell recognition and association. PMID- 4019587 TI - Interaction energies in lectin-induced erythrocyte aggregation. AB - Two N-acetylgalactosamine-reactive lectins, Helix pomatia (HPA) and Dolichos biflorus (DBA), were used to study the energies involved in cell-cell interactions through the specific binding of these lectins to their membrane receptors on genotype AO human erythrocytes (red blood cells) (RBCs). The energy required to dissociate a unit of aggregated membrane area (gamma d) of two RBCs bridged by lectin molecules was determined from the shear force needed to dissociate two-cell aggregates in a flow channel. When HPA were used as bridging molecules, gamma d (0.4 X 10(-4) to 3.8 X 10(-4) dyn/cm) was proportional to the density (D = 175 to 1,060 molecules/micron 2) of HPA molecules bound on the RBC membrane. A similar gamma d/D ratio was also obtained for DBA. These results indicate that the number of lectin molecules bound on the interface plays an important role in determining the energy required for cell-cell dissociation. The aggregation energy per unit membrane area (gamma a) in lectin-induced aggregates was calculated from the degree of encapsulation of a lectin-bound, heat-sphered human RBC by a normal discoid RBC. A minimum of approximately 1,800 HPA molecules/micron 2 on the spheres was required to form stable aggregates with the RBC. By using spheres having a surface HPA density of 1,830 to 2,540 molecules/micron 2, or 1.1-1.5 X 10(12) combining sites/cm2, the gamma a value for HPA-induced aggregation was found to be 2.2 X 10(-3) dyn/cm. This higher value of gamma a than gamma d has been explained on the basis of several differences in aggregation and disaggregation processes. The gamma a value for DBA-induced aggregation was not obtainable by the sphere encapsulation method because of the relative low D values. A comparison of the present results with the published value of the free energy change of 5 kcal/mol for the interactions of HPA and DBA with their ligands suggests that only a small fraction of the lectin molecules bound to RBC surface participate in the bridging of adjacent cells. PMID- 4019590 TI - Germination of stress-tolerant Eucalyptus pollen. AB - Earlier reports have indicated that the pollen of Eucalyptus is mechanically robust and unusually resistant to the osmotic stress imposed by immersion in water. We have investigated some of the features of the germination mechanism in the pollen of E. rhodantha with a view to clarifying the role of pollen-wall specializations in determining this resistance. Cultured in vitro, the pollen showed erratic germination, with a scatter of germination times up to 24 h. This was associated with variation between individual grains in the rate of hydration and dispersal of the pectins of the oncus, the thickened outer component of the intine present at each aperture. The oncus is itself differentiated, with a refractive outer layer lying within a sporopollenin operculum and itself overlying the protein-bearing layer of the intine. The outer layer, interpreted as a compacted pectin, undergoes only slow dissolution in aqueous media after the lifting of the operculum, and it is this that apparently protects the grain from the effects of short-term osmotic stress. The rate of dissolution varies between grains, possibly as a consequence of minor differences in developmental rate in the final stages of differentiation in the anther, and this contributes to the wider scatter of germination times. The dehydrated pollen gave one-third of the potential germination after 24 h exposure to 60 degrees C, and a small proportion survived 24 h at 70 degrees C. This degree of heat tolerance must primarily reflect properties of the protoplast of the vegetative cell, not examined in the present study; but the wall specializations may well provide a guard against extreme desiccation, and it is noteworthy that the function of the germination mechanism is not prejudiced by exposure to high temperatures. PMID- 4019589 TI - Chemotactic factor binding by metastatic tumour cells: evidence for a formyl peptide receptor on a non-myelogenous cell. AB - Analysis of fMet-Leu-[3H]Phe binding to Walker 256 carcinosarcoma cells demonstrated both saturable and reversible binding, and indicated the presence of a single population of binding sites having an equilibrium dissociation constant: KD = 15.7 +/- 3.3 X 10(-9) M, and with 2425 +/- 204 binding sites per cell. The specificity of the binding site was investigated by competitive inhibition of fMet-Leu-[3H]Phe binding studies using 10 oligoformyl peptides. These results demonstrated an order of peptide reactivity with marked similarity in specificity to the leucocyte binding sites for the formyl-peptides. The most active peptides also had potent agonist activity as determined by their ability to increase the cells' adherence response to nylon-wool fibres. In addition, a competitive antagonist of the formyl-peptide receptor, tert-butoxy-Phe-Leu-Phe-Leu-Phe, completely abolished the adherence response induced by fMet-Leu-Phe, but had no inhibitory effect on the adherence response caused by the tumour-promoting agent, phorbol myristate acetate. These data demonstrate that formyl-peptide receptors may be more common than we have anticipated and may be found on cells not derived from the myeloid series. Furthermore, these studies advance our understanding of stimulus-coupled responses in tumour cells. PMID- 4019588 TI - Selective packaging of human growth hormone into synaptic vesicles in a rat neuronal (PC12) cell line. AB - We have introduced the gene for human growth hormone (hGH) into PC12 cells, a rat pheochromocytoma-derived cell line with neuronal characteristics, and have isolated stable cell lines that express this protein. hGH is stored within the cells in membrane-bounded vesicles that are indistinguishable from the endogenous catecholaminergic synaptic vesicles. When the transfected cells are stimulated by carbachol or direct depolarization, they release norepinephrine and hGH with parallel kinetics. Treatment of the transfected cells with nerve growth factor results in a twofold increase in the amounts of hGH stored in and secreted from the cells. Not all proteins are packaged into the synaptic vesicles, since the rate of release of laminin, a soluble secreted protein endogenous to PC12 cells, is not stimulated by carbachol. This neuronal cell line therefore possesses at least two distinct pathways for secretion and can selectively package a foreign endocrine hormone into the regulated pathway. PMID- 4019591 TI - Manipulating chromosome structure and metaphase status with ultraviolet light and repair synthesis inhibitors. AB - DNA repair occurs in metaphase-arrested cells in response to ultraviolet irradiation. In the presence of the repair synthesis inhibitors hydroxyurea and 1 beta-D-arabinofuranosylcytosine the chromosomes of such cells, as seen in Carnoy fixed preparations, are decondensed. The extent of decondensation is related to both the u.v. dose and the duration of incubation in the presence of inhibitors. For any particular cell type there is a reasonable correlation between the amount of decondensation and the number of single-strand DNA breaks generated by the repair process under the same inhibitory conditions, though the chromosome changes continue after the number of single-strand breaks has reached a plateau. The dose response of chromosome decondensation varies between different cell types but is in general correlated with differences in levels of single-strand breaks accumulated under comparable inhibitory conditions. Decondensation can be detected after 0.5 Jm-2 in repair-competent human cells. In human cells defective in excision repair there is much less chromosome decondensation in response to the same u.v. dose and time of repair inhibition. However, a simian virus 40 transformed muntjac cell displays pronounced chromosome decondensation but has limited incision ability. Both chromosome decondensation and single-strand break accumulation in the presence of inhibitors are reversed when DNA precursors are provided, but reversal after higher u.v. doses and longer periods of incubation leads to recondensed chromosomes that are fragmented. Elution of the DNA from such cells through polycarbonate filters under non-denaturing conditions reveals that double-strand DNA breaks are generated during the period of incubation with inhibitors. Although the chromosomes of repair-inhibited metaphase cells are decondensed in fixed preparations, their morphology appears normal in intact cells. The cells also retain a capacity to induce prematurely condensed chromosomes (PCC) when fused with interphase cells: compared with control mitotic cells, the speed of induction is sometimes reduced but the final amount of PCC produced is similar. PMID- 4019592 TI - Human serotonectin: a blood glycoprotein that binds serotonin and is associated with platelets and white blood cells. AB - A glycoprotein that circulates in blood, binds to the surface of platelets, and also binds serotonin with high avidity and specificity, has previously been found in rats. This glycoprotein has been called serotonectin. We now report the purification and characterization of a similar circulating glycoprotein in human blood that we propose be called human serotonectin, to distinguish it from the rat protein. Human serotonectin binds serotonin with high affinity (Kd1 = 36 nM; Kd2 = 1.1 microM). Monospecific antisera were raised in rabbits to purified human serotonectin. These antibodies were used to locate human serotonectin immunocytochemically, for quantitative estimation of the glycoprotein, and for rapid preparation of material purified by affinity chromatography. Evidence was obtained that indicated that human serotonectin circulates in plasma and also binds to the surfaces of white blood cells and platelets but not to red blood cells. In bone marrow it is found on megakaryocytes and on developing white cells of the eosinophil line. The protein can be completely removed by washing with isotonic sucrose or salt solutions from the surfaces of white cells but similar treatment only partially (63% sucrose wash/73% salt wash) removes human serotonectin from platelets. Antibodies to human serotonectin antagonize the uptake of serotonin by platelets but do not inhibit platelet aggregation. These data show that humans, like rats, have a circulating serotonin-binding glycoprotein that is also present as a peripheral membrane protein on platelets. The human also differs from the rat serotonectin in binding to white cells. The material may function in platelet serotonin uptake in both humans and rats; however, its function, if any, with respect to white cells is obscure. PMID- 4019593 TI - Adult, foetal and transformed fibroblasts display different migratory phenotypes on collagen gels: evidence for an isoformic transition during foetal development. AB - Data are presented indicating that the migration of fibroblasts into three dimensional collagen gels is affected by cell density. We have defined a 'cell density migration index' (CDMI) to express this behavioural response in quantitative terms. The results of a survey of 77 different cell types indicate that the CDMI values expressed by normal adult skin fibroblasts and transformed cell lines fall into two distinct, non-overlapping groups. Measurement of the CDMI therefore provides an additional means of distinguishing between normal and transformed cells and may be used in conjunction with other commonly recognized criteria (e.g. anchorage-independent growth) to assess expression of a transformed phenotype in vitro. It is of interest to note that the CDMI values expressed by foetal cells define a group lying intermediate between normal and transformed cells. Both uncloned and cloned foetal cells have been observed to undergo a stable transition to expression of CDMI values characteristic of adult cells when followed throughout the duration of their in vitro lifespan. In addition to providing a novel means of distinguishing between normal adult and foetal cells, our results suggest that foetal fibroblasts undergo an 'isoformic' transition at some point in their developmental history, which is manifest in vitro by the expression of an adult CDMI. PMID- 4019594 TI - Skin fibroblasts obtained from cancer patients display foetal-like migratory behaviour on collagen gels. AB - When plated on the surface of collagen gel substrata, all types of fibroblasts rapidly begin to migrate down into the three-dimensional collagen matrix. We have previously demonstrated that normal (adult and foreskin), foetal and transformed fibroblasts may be distinguished from each other by virtue of their differential migratory response to changes in cell density. The effects of cell density on fibroblast migration into the gel may be expressed by a single numerical value, the 'cell density migration index' (CDMI). We now present evidence that ostensibly normal skin fibroblasts obtained from the majority of patients we examined with carcinoma of the breast, malignant melanoma, familial polyposis coli, retinoblastoma and Wilms' tumours display aberrant CDMI values falling within the foetal range. Skin fibroblasts obtained from the majority of patients examined with genetic or chronic diseases (e.g. rheumatoid arthritis, Duchenne muscular dystrophy) displayed CDMI values falling within the normal range. PMID- 4019595 TI - Incomplete contact site A glycoprotein in HL220, a modB mutant of Dictyostelium discoideum. AB - HL220, a modB mutant that lacks a modification of certain membrane proteins of Dictyostelium discoideum, has been shown to aggregate and to form EDTA-stable intercellular contacts typical of aggregating wild-type cells. A developmentally regulated glycoprotein of 80 X 10(3) apparent molecular weight has been identified as a target site of adhesion-blocking Fab and thought to be involved in EDTA-stable cell contact formation (Muller & Gerisch, 1978). In the HL220 mutant this glycoprotein is no longer recognized by a modB-specific antibody. Therefore, it has been suggested that the 80 X 10(3) Mr glycoprotein, or a modification on it, is not required for the EDTA-stable cell contact of aggregating cells. We show that HL220 synthesizes an equivalent of the 80 X 10(3) Mr glycoprotein with an apparent molecular weight of 68 X 10(3). The mutant product reacted with certain monoclonal antibodies highly specific for the 80 X 10(3) Mr glycoprotein in the wild type, and was developmentally regulated like the 80 X 10(3) Mr glycoprotein. These results indicate that the 68 X 10(3) Mr protein of the mutant lacks a modification, most likely an oligosaccharide residue, the absence of which causes the substantial shift of the apparent molecular weight from 80 X 10(3) to 68 X 10(3). Monoclonal antibodies that did not react with proteins of the mutant could be classified according to their reactions with different sub-sets of wild-type proteins. These results indicate that the proteins that reacted with either one or the other antibody were not modified by a uniform structure. The modification rather varies from one sub-set of cross-reacting proteins to another, suggesting differences between the glycosyl residues of the partially cross-reacting proteins. HL220 cells showed strongly reduced EDTA-stable contact formation under our conditions. EDTA sensitive intercellular adhesion was undetectable in the mutant, whereas adhesion of the cells to the substratum appeared to be strengthened. The rear ends of the cells, in particular, were tightly attached to glass or Teflon surfaces. The mutant cells were capable of responding chemotactically. Propagated excitation waves like those known to be based on periodic cyclic AMP production and relay were clearly seen. Extracellular phosphodiesterase induction by cyclic AMP and phosphodiesterase inhibitor production were normal. These results indicate that the generation of chemotactic signals and the cellular responses to cyclic AMP are not severely affected by the mutation. PMID- 4019596 TI - [Cystadenoma and cystadenocarcinoma of the pancreas. Apropos of 7 new cases]. AB - Cystadenomas and cystadenocarcinomas of the pancreas are tumours which remain poorly known because of their relative rarity. They are seen essentially in women aged between 40 and 60 and involve the left half of the pancreas more often than the right. The symptomatology remains latent for a fairly long time, which explains the fact that they are most often discovered only at the stage of a palpable tumour. Recent methods of investigation--echotomography and computed tomography--are of very great value in preoperative diagnosis. It is extremely important to draw the distinction within the group of benign cystadenomas between microcystic forms and macrocystic forms or mucinous cystadenomas, the latter having a definite potential for malignant change, possibly explaining the link with certain cystadenocarcinomas. As a result, excision surgery is always preferable, when possible, to bypass surgery, at least in caudal or corporeo caudal lesions, since excision surgery is usually easy. For cephalic lesions, if excision surgery seems difficult, it may be conceivable, using modern techniques of investigation, to adopt a conservative attitude when there are no features suggestive of potential malignant change. PMID- 4019598 TI - [Retrospective study of a series of 62 cases of hydatid liver cysts]. AB - Sixty-two cases of hydatid cyst of liver were treated and followed up between 1968 and 1982. Current pre-operative investigations include immunologic tests (immunoelectrophoresis, tests for hemagglutination inhibiting antibodies) and medical imaging (ultrasound, scanner). Vascular exploration is now very rarely performed. Surgical treatment is mainly by pericystectomy and was conducted in 90% of cases with a postoperative mortality of 5,2%. Chemotherapy with Albendazole was combined routinely. PMID- 4019597 TI - [Results of the surgical treatment of chronic external laxity of the ankle by resetting capsular ligamentous tension]. AB - The authors review 12 patients operated for tibio-tarsal instability and summarize the effects of ligamentous sections of the capsular-ligamentous plane of the lateral part of the ankle and the importance of the anterior peroneotalar fascia. In cases of tibio-tarsal instability, the authors propose a lateral ligamentous re-tension plasty with trans-osseous reinsertion and they analyse the results of this operation in a series of 13 operated ankles which were followed clinically and radiologically. The essential criterion of evaluation was a return to the same level of sports activity (7 very good results, 3 good results, 2 moderate results and one failure). The overall favourable results suggest that this technique can be indicated in a number of rare cases: sportsmen with significant disability after failure of treatment by proprioceptive re-education. In conclusion, the authors stress the value of preventative treatment of sprained ankles, which should prevent the development of instability. PMID- 4019599 TI - [Superficial cancer of the stomach]. AB - The authors report 17 cases of superficial carcinomas collected amongst a series of 100 gastric carcinomas. Three principal points are analysed: clinical picture, diagnostic and treatment. Clinical problems indicate the multiplicity of classifications used and their sometimes incomplete nature. This led the authors in 1970 to develop a classification with 4 parameters, derived from the T N M classification and from that of Gutmann. The diagnostic problems raises yet again for these superficial carcinomas the need for routine screening which is the only way to increase early diagnoses, and hence the effectiveness of treatment. The therapeutic problem is concerned with the discussion of the limitations of wide excision as a matter of principle. PMID- 4019600 TI - [Traumatic rupture of the middle lobe bronchus and pulmonary artery: considerations apropos of a case]. AB - The authors report the case of a road accident which resulted in rupture of the middle lobe bronchus. There was an associated lesion of the pulmonary artery. Treatment was conservative after primary evaluation of the right pulmonary artery at its origin. Vascular trauma associated with rupture of the main bronchi is rare. The prevalence is greater in the case of rupture of the more distal lobar bronchi. It is important to be aware of this possibility, and the pulmonary artery must be inspected before such lesions are treated surgically. PMID- 4019601 TI - [Cancer of the so-called "gastric stump". Review of the literature apropos of 4 cases]. AB - On the basis of four cases of cancer of the stomach occurring after surgery for benign gastroduodenal lesions, the authors analyse 1690 cases published in the literature. The development of these cancers, which occur much more frequently than in the normal population, is favoured by all of the local pathophysiological consequences of the initial operation, although no one factor is predominant. These cancers have a very poor prognosis, with a mean 5 year survival of 6.9%. These very disappointing results can only be improved by early detection as a result of systematic endoscopic follow-up. PMID- 4019602 TI - [Construction of a plaster collar]. AB - A fairly simple but strictly controlled method is described for constructing a plaster collar. After a brief description of the apparatus, meticulous details are given of each technical step leading to the production of a light, perfectly molded and well tolerated apparatus. The collar is usually constructed with the patient sitting, under slight traction and with webbing straps to obtain immobilization in the exact position required. The shoulders are lowered to a maximum by making the patient hold weights. The cephalic part is first molded and then integrated solidly into the thoracic part (breastplate and backplate). A perfectly constructed apparatus provides excellent immobilization. PMID- 4019603 TI - The relation between grammatical development and mean length of utterance in morphemes. PMID- 4019604 TI - The child language data exchange system. PMID- 4019605 TI - Language differentiation by the bilingual infant. PMID- 4019606 TI - The emergence of present perfect verb forms: semantic influences on selective imitation. PMID- 4019607 TI - A tip-of-the-tongue experience at age two? PMID- 4019608 TI - Some contributions of mothers' speech to their children's syntactic growth. PMID- 4019609 TI - Colour-name versus shape-name learning in young children. PMID- 4019610 TI - 'He has too much hard questions': the acquisition of the linguistic mass-count distinction in much and many. PMID- 4019611 TI - Five-year-olds' understanding of 'savoir' and 'croire'. PMID- 4019612 TI - Is the English present progressive unique. PMID- 4019614 TI - How does comprehension of passive develop? A comparison of actional and experiential verbs. PMID- 4019613 TI - Comprehension of Icelandic pronoun gender: semantic versus formal factors. PMID- 4019615 TI - Incomplete and continuing: theoretical issues in the acquisition of tense and aspect. PMID- 4019616 TI - How much do children say in a day? PMID- 4019617 TI - IQ, scholastic performance and behaviour of sibs raised in contrasting environments. AB - Medium- and long-term effects of types of placement of the offspring of lower class families have been studied. The progeny of 28 mothers was reconstituted. The subjects were divided into three groups: 35 children abandoned and adopted early in privileged environments (A), 46 'biological mother-reared' children remaining in their disadvantaged social environments (B) and 21 children raised in institutions or foster homes (C). Analyses focused on IQ, scholastic performance and behaviour. Results show that the social environment has important effects: the differences between the three groups are very significant. For A and B groups tested in the schools, comparisons were made with the classmates. For the C group the effects of long-term emotional deprivation are superimposed on the effects of the social environment. PMID- 4019618 TI - Behavioural methods in the treatment of sleep disorders--a pilot study. AB - The efficacy of behavioural methods of treatment for severe sleep disorders was examined in a pilot study involving 35 children aged 1-5 years. Improvement occurred in 77%. Methodological issues concerning the selection of children for treatment, selecting adequate controls and outcome measures, and using parents as therapists, are discussed. PMID- 4019619 TI - The nature and qualities of parenting provided by women raised in institutions. AB - A repeated pattern of difficulties in parenting is often found in successive generations of the same families. That finding, together with a concern to identify potential adverse influences upon child behaviour and development, was the focus of this study into the parenting provided by women who were raised within institutions. Relationships with their 2- to 3-year-old infants were assessed using complementary interview and naturalistic observational techniques. Differences in parenting styles between the case and comparison groups were on the whole subtle. Ex-care women were relatively less sensitive to their children's cues and, in response to their demands and opposition, exercised control by confrontation rather than by circumvention. PMID- 4019620 TI - Continuities in sibling relationships: patterns of aggression and friendliness. AB - Thirteen girls and 12 boys who had been observed at home as 2- to 3-year-olds with their mothers and infant siblings were interviewed as 6-year-olds about their relationship with their siblings; their mothers also were interviewed. The marked individual differences found among the 2- to 3-year-olds in comments about their siblings were correlated with differences in the children's comments about their siblings 3-4 years later, and the differences in their behaviour towards their siblings as 2- to 3-year-olds were correlated with differences in their mothers' accounts of the sibling relationship at the 6-year visits. PMID- 4019621 TI - Influence of Yoruba beliefs about abnormality on the socialization of deaf children: a research note. AB - The study examines patterns of communication modes of guidance and discipline and affectional bonds between 176 Yoruba hearing mothers and their deaf children. Results relating to communication support earlier findings about the frustrations inherent in such endeavour. Contrary to other published reports, the Yoruba mothers studied perceived expressive linguistic abilities of deaf children more negatively than receptive abilities. Communication difficulties affected mothers' guidance and discipline, particularly since the culturally preferred modes of discipline rely very heavily on children's age-related language competence. Mothers' verbal claims of affectional bonds were not supported by evidence from other sources close to and including the deaf children. PMID- 4019622 TI - Electrodermal activity of undersocialized aggressive children: a pilot study. AB - Electrodermal activity of 11 children with conduct disorder (CD) and 11 normal children were compared during periods of rest, moderate tone and loud bell stimulation. The CD group was best differentiated from controls by lower reactivity to the first bell, while on tonic measures they showed normal values. The electrodermal profile of the CD children thus resembled that of adult sociopaths on phasic measures only. The possibility of using electrodermal measures for predicting outcome and for differential diagnosis is raised. PMID- 4019623 TI - [Application of electrochemical detection to the analysis of some residues of carbamate insecticides by high performance liquid chromatography]. AB - A new high-performance liquid chromatographic determination of residues of some carbamate insecticides with electrochemical detection after degradation of molecules as the phenols is described. Residues of carbamate insecticides in vegetables can be quantified with high sensitivity. PMID- 4019624 TI - High-performance liquid chromatographic determination of d-/l-epinephrine enantiomer ratio in lidocaine-epinephrine local anesthetics. AB - A procedure for the determination of the ratio of d- to l-epinephrine in lidocaine-epinephrine local anesthetics is described. Epinephrine was isolated via Sep-Pak cartridges and derivatized with 2,3,4,6-tetra-O-acetyl-beta-D glucopyranosyl isothiocyanate; the d- and l-chiral derivatives were separated and measured by high-performance liquid chromatography. About 70 samples of various dosage forms and concentrations from four manufacturers were successfully analyzed by the method. PMID- 4019625 TI - Improvement of chemical analysis of antibiotics. VIII. Application of prepacked C18 cartridge for the analysis of tetracycline residues in animal liver. AB - A simple, rapid and precise analytical method for tetracycline (TC) residues in the liver of slaughtered animals has been established. The recoveries of oxytetracycline (OTC), TC, chlortetracycline (CTC) and doxycycline (DC) from beef liver spiked at the level of 1.0 ppm were 87.7, 87.5, 79.6 and 67.5% with coefficients of variations of 1.01-2.87%. Detection limits in beef liver were 0.05 and 0.1 ppm for OTC and TC and for CTC and DC, respectively. It is also possible to apply this method to the analysis of residual TCs in various foods with the same recovery, accuracy and detection limits as in the case of beef liver. PMID- 4019626 TI - Gas chromatographic patterns of some apple surface wax constituents. PMID- 4019627 TI - Quantitation of caffeine in doping analysis using an automated extractor/concentrator. PMID- 4019628 TI - High-performance liquid chromatographic determination of adenine nucleotides in biological materials. Improvements and adaptations to routine analysis. PMID- 4019629 TI - Improved method for gas chromatographic determination of phytanic acid. PMID- 4019630 TI - Determination of preservatives in cosmetic products by reversed-phase high performance liquid chromatography. II. PMID- 4019631 TI - Production of mutagenic artifacts by the action of residual chlorine on XAD-4 resin. AB - XAD resins are commonly used to recover and concentrate organics from chlorinated water. It was found that the action of residual chlorine on XAD-4 resin produced mutagenic artifacts in a dose dependent manner. The production of mutagenic artifacts could be suppressed at least ten-fold by converting free chlorine to monochloramine. Kinetic studies of the reaction between free chlorine and XAD-4 resin showed a reaction rate dependence upon pH and chloride ion concentration that suggests participation of species besides hypochlorous acid. PMID- 4019632 TI - Thin-layer chromatographic screening procedure for undeclared synthetic drugs in Chinese herbal preparations. AB - A simple and rapid thin-layer chromatographic procedure was developed for the detection and presumptive identification of seventeen synthetic drugs previously reported as adulterants of Chinese herbal preparations. Depending on its complexity, the sample may be directly extracted into aqueous ethanol, or stepwise fractionated into acidic, basic, and neutral components. Extracts are analyzed on silica gel layers containing a fluorescent indicator with the aid of two solvent systems. Spots are visualized under short and long wavelength ultraviolet lights. The procedure was successfully tested on synthetic and commercial samples. PMID- 4019633 TI - High-performance thin-layer chromatographic analysis of dialysable materials in allergen extracts. PMID- 4019634 TI - Determination of paracetamol, salicylic acid and acetyl salicylic acid in serum by high-performance liquid chromatography. PMID- 4019635 TI - Simple method for the determination of diaminopimelic acid in rumen liquor hydrolysates. PMID- 4019636 TI - A method for the determination of S-methylcysteine by high-performance liquid chromatography: application to the study of carcinogenic methylating agents. PMID- 4019637 TI - Formation and metabolism of pungent principle of Capsicum fruits. XV. Microdetermination of capsaicin by high-performance liquid chromatography with electrochemical detection. AB - A new, highly sensitive method for quantitative separation and determination of capsaicin and dihydrocapsaicin by high-performance liquid chromatography with electrochemical detection is elaborated. The method employs a Cosmosil 5Ph column eluted with 100 mM potassium dihydrogenphosphate containing 45% acetonitrile (pH 5.0) at a flow-rate of 1.0 ml/min, and an electrochemical detector (at a potential of +750 mV versus the Ag/AgCl electrode). The detection limits for both capsaicin and dihydrocapsaicin were 12 pg (39 fmol) at a signal-to-noise ratio of 3:1. By applying this method, the biological half-life of capsaicin in the rat was investigated. PMID- 4019638 TI - Determination of isoniazid, acetylisoniazid, acetylhydrazine and diacetylhydrazine in biological fluids by high-performance liquid chromatography. AB - A high-performance liquid chromatographic assay for the determination of isoniazid, acetylisoniazid, acetylhydrazine and diacetylhydrazine (plasma and urine) was developed. The m-chlorobenzoyl derivatives of isoniazid, acetylhydrazine and the internal standard propionylhydrazine were prepared, separated on a RP-18 column and detected at 220 nm. Acetylisoniazid, diacetylhydrazine and the internal standard dipropionylhydrazine were converted to isoniazid, acetylhydrazine, and propionylhydrazine by acidic hydrolysis and subsequently derivatized with m-fluorobenzoyl chloride, separated on a RP-18 column and detected at 220 nm. The lower limits of detection in plasma are acetylhydrazine 0.5 nmol/ml, isoniazid 1.0 nmol/ml, diacetylhydrazine 1.0 nmol/ml and acetylisoniazid 2.0 nmol/ml, and in urine, acetylhydrazine 10 nmol/ml, isoniazid 15 nmol/ml, diacetylhydrazine 20 nmol/ml and acetylisoniazid 40 nmol/ml. This method is sensitive, reproducible, accurate and precise; therefore, it is well suited for detailed pharmacokinetic studies. PMID- 4019639 TI - Quantitative determination of tolazoline in serum and urine. AB - A high-performance liquid chromatographic procedure is described for the analysis of tolazoline in serum and urine. This assay procedure is suitable for the analysis of micro-samples (50 or 100 microliters serum and 100 microliters urine). Samples are extracted in a single step and injected into a reversed-phase high-performance liquid chromatography system for detection at 210 nm. The clinical applicability of this assay is demonstrated by the determination of tolazoline serum and urine concentrations in neonates. In addition, the presence of urine conjugates and the extent of serum protein binding were investigated. This assay procedure has the required sensitivity (0.1 microgram/ml), accuracy and precision for both routine monitoring and pharmacokinetic characterization of tolazoline in neonates and adults. PMID- 4019640 TI - Analysis of meperidine and normeperidine in serum and urine by high-performance liquid chromatography. AB - A high-performance liquid chromatographic method is described for the simultaneous analysis of meperidine and normeperidine in serum and urine. A 1-ml sample aliquot is extracted into hexane, then back-extracted into a small volume of dilute acid which is injected onto a cyanopropyl analytical column. Absorbance of the column effluent is monitored at 205 nm. Two internal standards are employed, diphenhydramine for meperidine and nordiphenhydramine for normeperidine. Chromatography of the four compounds takes 4 min. Serum concentration--time curves of meperidine and normeperidine are presented for eight healthy subjects following single 70-mg bolus injections of meperidine. PMID- 4019641 TI - High-performance liquid chromatographic determination of diclofenac and its monohydroxylated metabolites in biological fluids. AB - Sensitive and selective high-performance liquid chromatographic assays for diclofenac and its monohydroxylated metabolites in biological fluids are described. Using ultraviolet detection at 282 nm, diclofenac is assayed in plasma at concentrations down to 10 ng/ml; total (free + conjugated) diclofenac and its monohydroxylated metabolites (the sum of 3'- + 4'-hydroxydiclofenac and 5 hydroxydiclofenac) are assayed in urine after chemical hydrolysis at concentrations down to 200 ng/ml. The applicability of the described assays is shown. PMID- 4019642 TI - Urinary excretion of N-acetylamino acids. PMID- 4019644 TI - Determination of bile acids in rat bile by high-performance liquid chromatography. PMID- 4019643 TI - Determination of adult sheep plasma catecholamines using [3H]norepinephrine as the internal standard. PMID- 4019645 TI - Rapid and simple method for quantitative determination of non-protein sulphydryls in mouse liver by reversed-phase high-performance liquid chromatography. PMID- 4019646 TI - High-performance liquid chromatographic analysis for fluorescein and fluorescein monoglucuronide in plasma. PMID- 4019647 TI - Simultaneous high-performance liquid chromatographic assay for 5-(2-bromo-E ethenyl)-2'-deoxyuridine and its metabolite, 5-(2-bromo-E-ethenyl)uracil, in plasma. PMID- 4019648 TI - Determination of amoxapine and metabolites in plasma by liquid chromatography with electrochemical detection. PMID- 4019649 TI - Determination of apomorphine in rat plasma and brain by high-performance liquid chromatography with electrochemical detection. PMID- 4019650 TI - Analysis of the toxicologically relevant metabolites of phenytoin in biological samples by high-performance liquid chromatography. PMID- 4019651 TI - Timolol determination in plasma and urine by high-performance liquid chromatography with ultraviolet detection. PMID- 4019652 TI - Gas chromatographic profiling of phenolic acids in urine of patients with cirrhosis of the liver. AB - Phenolic acids are analysed within the profile of the organic acids in urine of patients with cirrhosis. For the following constituents an increased urinary excretion is observed: 4-hydroxyphenylpyruvic acid, 4-hydroxyphenyllactic acid, 4 hydroxyphenylacetic acid, 4-hydroxybenzoic acid, 4-hydroxyhippuric acid, vanillic acid, homovanillic acid, 4-hydroxymandelic acid, 4-hydroxy-3 methoxyphenylpropionic acid and p-cresol. The phenols are metabolites of tyrosine and are produced in the liver, in extrahepatic tissues and by intestinal microorganisms. They are suggested as biochemical control parameters for the metabolizing function of the liver, for the effect of therapy and for the existence of portal-systemic venous collaterals. PMID- 4019653 TI - High-performance liquid chromatographic determination of 3-hydroxymethyl dibenzo[b,f]thiepin 5,5-dioxide and its acid metabolite in human plasma and urine. PMID- 4019654 TI - Determination of piperine in biological tissues by thin-layer chromatography and ultraviolet absorption densitometry. PMID- 4019655 TI - N-Methylation and N,N-dimethylation of amino acids. An artifact production in the analysis of organic acids using diazomethane as derivatizing agent. AB - In the fractions of the methyl esters of urinary organic acids seventeen N methylated or N,N-dimethylated amino acid methyl esters are identified by gas chromatography-mass spectrometry. It is shown for twelve amino acids that their amino group reacts with diazomethane to form these derivatives. Using deuterated reagents, in particular deuterated diazomethane, in the sample preparation procedure during the organic acid analysis, it is shown that the N-methylated and N,N-dimethylated amino acids are artifacts from diazomethane and are not biochemical N-methylation products. PMID- 4019656 TI - Comparative evaluation of the radioenzymatic method for the determination of urinary histamine with a mass spectrometric assay. AB - Considerable inaccuracy and unreliability have recently been demonstrated to be associated with the widely used radioenzymatic methods for the determination of histamine in biological fluids. Urine appears to inhibit the methylation of histamine by histamine N-methyltransferase such that the radioenzymatic assay underestimates the concentration of histamine present in urine. Directly comparing the radioenzymatic assay with a recently developed reference method using mass spectrometry for the determination of urinary histamine, up to 34-fold differences in the levels of urinary histamine were found with the two methods. PMID- 4019657 TI - New application of high-performance liquid chromatography for analysis of urinary C-peptide. AB - A successful application of high-performance liquid chromatography for analysis of urinary C-peptide is described. Samples (1.0 ml of human urine) were first subjected to gel chromatography to remove interfering substances, and then applied to a reversed-phase column (LiChrosorb RP-18, 7 micron). The detection of C-peptide was performed using a highly specific radioimmunoassay. With the newly developed techniques, at least four forms of immunoreactive C-peptide were detected in human urine. One of these peptides was indistinguishable from authentic C-peptide. The present study has clearly demonstrated the heterogeneity of urinary C-peptide. PMID- 4019658 TI - Quantitative analysis of veralipride in plasma and urine by gas chromatography mass spectrometry and gas chromatography with flame-ionization detection. AB - A highly sensitive and selective quantitative assay for unchanged veralipride has been developed. The compound is extracted from alkalized samples (plasma or urine) with dichloromethane and converted to its trimethylated derivative by reaction with trimethylanilinium hydroxide. The reaction mixture is then chromatographed on a 3% OV-1 column. Trimethylated derivatives of plasma samples were assayed by selected-ion monitoring in the chemical-ionization mode and quantified by comparing the intensity of the quasi-molecular ion m/z 426 (M + H) with the intensity of the corresponding ion from trideuterated internal standard, m/z 429 (M + H). Flame-ionization detection was used for the assay of urine samples. The peak height ratio of trimethylated veralipride over trimethylated sulpiride, the internal standard, was used for quantitation of urine samples. A relative standard deviation of less than 10% was found when quantifying 10 ng/ml veralipride in plasma or 1 microgram/ml in urine. PMID- 4019659 TI - Analysis of buprenorphine and its N-dealkylated metabolite in plasma and urine by selected-ion monitoring. AB - A selected-ion monitoring method was developed for determination of buprenorphine and its N-dealkylated metabolite (norbuprenorphine) in human plasma and urine. N Propylnorbuprenorphine was added as internal standard to 2-3 ml of sample and the alkaloids were extracted with toluene-2 butanol at pH 9.4. After back-extraction in dilute sulphuric acid, the compounds were heated at 110 degrees C. This procedure led to quantitative loss of methanol followed by ring formation between the 6-methoxy group and the branched side-chain of all compounds. The derivatives were extracted into dichloromethane-2-butanol and treated with pentafluoropropionic anhydride. The resulting derivatives were suitable for selected-ion monitoring analysis. The coefficient of variation was found to be 4.5% at 5 ng/ml and 8.9% at 50 ng/ml in urine. The corresponding values for plasma were 6.2% and 5.3%, respectively. The lower limit of detection in plasma was 150 pg/ml, permitting analysis of plasma levels of buprenorphine for 24 h and urine levels of buprenorphine and norbuprenorphine for more than seven days after a therapeutic dose of buprenorphine. This method is the first with sufficient specificity and sensitivity for characterization of the clinical pharmacokinetics of buprenorphine. PMID- 4019660 TI - Determination of dextromethorphan and metabolites in human plasma and urine by high-performance liquid chromatography with fluorescence detection. AB - Sensitive methods were developed for the analysis of dextromethorphan (I) and two metabolites, (+)-17-methyl-morphinan-3-ol (II) and (+)-morphinan-3-ol (III), in plasma as well as dextromethorphan and three metabolites II, III and (+)-3 methoxymorphinan (IV) in urine using high-performance liquid chromatography followed by detection with a fluorometer. Dextromethorphan and its metabolites were extracted from plasma and urine and separated in the reversed-phase mode. The practical lower limits of determination for I, II, and III in plasma were 0.5, 5, and 5 ng/ml, respectively; for I, II, III, and IV in urine, the limits were 20 ng/ml, 0.6 microgram/ml, 0.5 microgram/ml, and 15 ng/ml, respectively. The linearity of the calibration graphs was excellent (r varied from 0.9994 to 0.9999) over concentration ranges of two orders of magnitude. PMID- 4019661 TI - Determination of promethazine in human plasma by automated high-performance liquid chromatography with electrochemical detection and by gas chromatography mass spectrometry. AB - A highly specific and sensitive method using automated high-performance liquid chromatography with electrochemical detection (HPLC-ED) and a method using gas chromatography-mass spectrometry (GC-MS) have been developed for the quantitative determination of promethazine in plasma. The lowest detectable concentration by HPLC-ED is 0.1 ng/ml of plasma and by GC-MS 0.5 ng/ml of plasma. The HPLC-ED method incorporates a valve switching unit to prevent all of the electroactive impurities from entering the electrode compartment, thus maintaining the sensitivity of the detector for the analyses of large numbers of samples. The GC MS method incorporates the highly specific selected-ion monitoring technique. Plasmas derived from healthy subjects each given a single 50-mg oral dose of promethazine were analyzed by both HPLC-ED and GC-MS. The two methods compare favorably with a correlation coefficient of 0.92 and a slope of 1.059. While both methods are suitable for studying single-dose pharmacokinetics of promethazine, the automated HPLC-ED method has a decided advantage in being more sensitive and suitable for unattended overnight analyses of the large number of samples encountered in pharmacokinetic studies. The specificity of the HPLC-ED method is demonstrated by comparison to the GC-MS analysis of biological samples. PMID- 4019662 TI - Metabolic studies of explosives. II. High-performance liquid chromatography-mass spectrometry of metabolites of 2,4,6-trinitrotoluene. AB - A series of metabolites of 2,4,6-trinitrotoluene were studied by combined high performance liquid chromatography-mass spectrometry. These metabolites are formed mainly by oxidation and reduction processes. Separations were done on a C8 reversed-phase column, using acetonitrile-water at various relative concentrations as mobile phases, followed by ultraviolet and on-line mass spectrometry with a direct liquid insertion probe liquid chromatograph-mass spectrometer interface. The mass spectra obtained were chemical-ionization spectra with the mobile phase as reagent. Mass spectra obtained included mainly reduced ions, adduct ions and typical fragment ions. The combination of high performance liquid chromatographic separation with on-line mass spectrometry was found to be a suitable method for the identification of the investigated metabolites. PMID- 4019663 TI - Determination of cimetidine and metabolites in plasma by reversed-phase high performance liquid chromatographic radial compression technique. AB - A high-performance liquid chromatographic method for the detection of cimetidine and its metabolites in plasma was developed which has a short analysis time and good resolution. The total analysis time was approximately 11 min. The standard curves were linear over the concentrations used for all compounds and the sensitivity limits were good. The coefficient of variation for within-day and between-day analysis was less than 4.2% for all compounds with the exception of guanyl urea cimetidine, which was approximately 10%. Currently, this assay is being used in a pharmacokinetic study of plasma and gastric aspirate samples obtained from a critically ill pediatric population. PMID- 4019664 TI - Determination of nitrazepam and its main metabolites in urine by thin-layer chromatography and direct densitometry. AB - A method for the direct quantitative densitometry of nitrazepam and its main metabolites (7-aminonitrazepam, 7-acetamidonitrazepam and 2-amino-5 nitrobenzophenone) in urine was developed. The unchanged drug and its metabolites were extracted with benzene-dichloromethane (4:1), subjected to thin-layer chromatography, and determined by direct ultraviolet densitometry. Recovery experiments showed that the method was quantitative. The limit of detection was 5 ng/ml for 2-amino-5-nitrobenzophenone and 10 ng/ml for other compounds. The method was applied to the determination of nitrazepam and its metabolites excreted in human urine after administration of 10 mg of the drug. PMID- 4019665 TI - Improved analysis of acetylcholine and choline in canine brain and blood samples by capillary gas chromatography-mass spectrometry. PMID- 4019666 TI - Determination of diprobutine in human plasma using gas-liquid chromatography with nitrogen-selective detection. PMID- 4019667 TI - Micro high-performance liquid chromatographic assay of acetaminophen and its major metabolites in plasma and urine. PMID- 4019668 TI - Improved assay procedure for tripamide in blood. PMID- 4019669 TI - Assay of lipids in dog myocardium using capillary gas chromatography and derivatization with boron trifluoride and methanol. AB - The fatty acids of three lipid classes (free fatty acids, triglycerides, and cholesteryl esters) from dog heart were analysed by gas chromatography. Samples of the left ventricle were homogenized and total lipids were extracted. After separation by thin-layer chromatography, the bands of the lipid classes studied were scraped off, transmethylated according to the boron trifluoride-methanol procedure, and the fatty acid methyl esters were extracted and analysed. The problems related to the quantitation of fatty acids were investigated, namely transmethylation procedure, thin-layer chromatography, and gas chromatographic conditions. Fatty acid methyl esters were separated on capillary columns coated in the laboratory with SP 2340 stationary phase. The high performance of the separation ensured the reliability and the precision of the analysis. PMID- 4019670 TI - High-performance liquid chromatography of cardiolipin. AB - Resolution of freshly prepared and of commercially available (degraded) samples of cardiolipin into 15-30 components has been accomplished by reversed-phase high performance liquid chromatography using a 3-micron particulate Microsorb C18 column irrigated with linear gradients of acetonitrile--methanol--10 mM phosphate buffer pH 7.4. Selected resolved components were crystallized and characterized by infrared absorption spectra. Saponification of other components and identification of component fatty acids by reversed-phase high-performance liquid chromatography demonstrated the presence of ten fatty acids (14:0, 14:1, 16:0, 16:1, 18:0, 18:1, 18:2, 18:3, 20:0, 20:4), with linoleic acid (18:2) identified in all resolved components. From fatty acid composition data it appears that several resolved fractions consist of single cardiolipin molecular species. PMID- 4019671 TI - Simplified procedure for specific determination of imino acids in human blood plasma by high-performance liquid chromatography. AB - After deproteinization with 70% aqueous ethanol and evaporation to dryness, a plasma sample was subjected to the formol reaction. Then Dns derivatization of imino acids was carried out for 20 min at 37 degrees C. An aliquot of the resulting solution was subjected to reversed-phase chromatography using continuous gradient elution with acetonitrile-50 mM acetate buffer (pH 4.0) as solvent system. This method is selective for imino acids. Hydroxyproline and proline levels could be determined using 30 microliter of plasma. PMID- 4019673 TI - Drug level monitoring. PMID- 4019672 TI - Application of a capillary gas chromatographic-selected-ion recording mass spectrometric technique to the analysis of diethylstilbestrol and its phosphorylated precursors in plasma and tissues. AB - A method for the analysis of diethylstilbestrol (DES) which is suitable for pharmacokinetic studies has been developed using capillary gas chromatographic (GC) separation and detection with selected-ion mass spectrometry (MS). This technique has been applied to a variety of samples including human plasma samples and extracts of animal tissues including prostate and liver. To investigate the pharmacokinetics of stilphostrol (diethylstilbestrol diphosphate) we have modified the GC-MS method in two ways. One modification involves a dual assay for DES; the first a direct assay, and the second after hydrolysis of a sample with alkaline phosphatase. The difference in these values is the amount of phosphorylated DES present. The other modification separates stilphostrol and DES using a reversed-phase, ion-paired high-performance liquid chromatographic method followed by alkaline phosphatase hydrolysis followed by the GC-MS method. The details of these three methods are described and some representative data are shown. PMID- 4019674 TI - Identification of metabolites diagnostic for organic acidurias by simultaneous dual-column capillary gas chromatography. AB - To offer a procedure with increased resolution compared to packed-column gas chromatography, we developed a dual-capillary method of gas chromatography for diagnosing organic acidurias. We derivatized and injected organic acids repeatedly on two different bonded phase columns (DB-1, DB-1701) to establish a table of methylene units. Compounds in urine specimens were identified by their characteristic pair of methylene units. With this method, we are able to identify 120 metabolites in urine. Accordingly, the procedure provides a cost-effective alternative to routine gas chromatography-mass spectrometry. PMID- 4019675 TI - Determination of proquazone and its m-hydroxy metabolite by high-performance liquid chromatography. Clinical application: pharmacokinetics of proquazone in children with juvenile rheumatoid arthritis. AB - A method for the determination of proquazone and its m-hydroxy metabolite in serum and urine by reversed-phase high-performance liquid chromatography is described. The technique is based on a single extraction of the unchanged drug, its metabolite and an internal standard from serum or urine with chloroform. The column was packed with mu Bondapak C18 and the mobile phase was acetonitrile- water (50:50) (pH 3). The detection limits for proquazone and its metabolite were 0.02 mumol/l using 500 microliters of sample. For the determination of the total m-hydroxy metabolite only 100 microliters of sample are needed. The method described is suitable for routine clinical and pharmacokinetic studies. The clinical application of this method suggests that the pharmacokinetics of proquazone in adults and children are similar. PMID- 4019676 TI - Determination of amino acids by separation of their ion pairs with dodecyl sulphate. AB - The ion pairs of amino acids with dodecyl sulphate were separated on a reversed phase column (Beckman Ultrasphere I.P.) using a sequence of eluents that are prepared by mixing 0.2 M phosphoric acid (containing 10 mM sodium dodecyl sulphate), 0.2 M sodium acetate (pH 4.50; containing 10 mM sodium dodecyl sulphate) and methanol. the amino acids commonly occurring in tissues, except taurine and related weakly basic amino acids, can be analysed at a rate of 95 min per sample at a sensitivity of less than 50 pmol per amino acid. Elution modes for specific amino acids (alpha-difluoromethylornithine, gamma-vinyl-4 aminobutyric acid, 4-aminobutyric acid, putreanine) and non-essential amino acids that allow higher separation rates are reported. The method is suitable for fully automated routine amino acid analysis. PMID- 4019677 TI - Determination of desferoxamine and a major metabolite by high-performance liquid chromatography. Application to the treatment of aluminium-related disorders. AB - A high-performance liquid chromatography method is described that permits separation and quantification of desferoxamine, a major metabolite, the iron(III) and the aluminum(III) chelates of desferoxamine. This method now facilitates pharmacokinetic studies on desferoxamine and derivatives designed to study side effects and metabolite patterns in patients undergoing treatment. PMID- 4019678 TI - Determination of fatty acids of the bacteria Streptomyces R61 and Actinomadura R39 by capillary gas chromatography-mass spectrometry. PMID- 4019679 TI - Unusual fatty acids from amniotic fluid phospholipids. PMID- 4019680 TI - Rapid separation of plasma lipoproteins by gel permeation chromatography on agarose gel Superose 6B. PMID- 4019681 TI - Routine determination of unconjugated 3-methoxy-4-hydroxyphenylglycol in plasma using high-performance liquid chromatography with electrochemical detection. PMID- 4019682 TI - Assay of urinary phenylacetic acid by high-performance liquid chromatography. PMID- 4019683 TI - Simple and sensitive assay of dopamine beta-hydroxylase in human cerebrospinal fluid by high-performance liquid chromatography with electrochemical detection. PMID- 4019684 TI - Quantitative high-performance liquid chromatography of bases and nucleosides in cerebral DNA of rat foetus. PMID- 4019685 TI - Ion-pair high-performance liquid chromatographic determination of isoniazid and acetylisoniazid in plasma and urine. Application for acetylator phenotyping. PMID- 4019686 TI - Simultaneous determination of serum vitamin A and E by liquid chromatography with fluorescence detection. PMID- 4019687 TI - Determination of propisomide, a new antiarrhythmic agent, in biological samples by gas chromatography with a thermionic detector. PMID- 4019688 TI - Separation of the enantiomers of intact sulfate conjugates of adrenergic drugs by high-performance liquid chromatography after chiral derivatization. PMID- 4019689 TI - High-performance liquid chromatographic method for the determination of bromodeoxyuridine and its major metabolite, bromouracil, in biological fluids. PMID- 4019690 TI - Measurement of meptazinol in plasma by high-performance liquid chromatography with electrochemical detection. PMID- 4019691 TI - Highly sensitive assay for choline acetyltransferase activity by high-performance liquid chromatography with electrochemical detection. AB - A highly sensitive assay for choline acetyltransferase activity by high performance liquid chromatography with electrochemical detection was devised. This assay method is based on the separation of acetylcholine and choline on a Develosil Ph-5 reversed-phase column (a phenyl column), followed by their enzymatic conversion to hydrogen peroxide through post-column reaction with acetylcholinesterase and choline oxidase. The sensitivity of the system is excellent and 5 pmol of acetylcholine enzymatically formed could be detected. The linearity between the peak height and the amount of acetylcholine was observed over the range of 5 pmol to 5 nmol. Some enzymatic properties were investigated by using a soluble fraction of bovine caudate nucleus as enzyme. The Michaelis constants of the enzyme for choline and acetyl coenzyme A were 0.3 mM and 0.03 mM, respectively. The enzyme exhibited the maximum activity over the pH range 7.4 9.5. The regional distribution of choline acetyltransferase activity in rat brain was examined. The order of the activity from the highest to the lowest agreed with the reported brain distribution of the enzyme: striatum, pons plus medulla oblongata, cerebral cortex, thalamus plus hypothalamus, olfactory bulb and cerebellum. PMID- 4019692 TI - Quantitative analysis of vigabatrin in plasma and urine by reversed-phase high performance liquid chromatography. PMID- 4019693 TI - Quantitation of levorphanol in plasma using high-performance liquid chromatography with electrochemical detection. PMID- 4019694 TI - Quantitative determination of perphenazine and its dealkylated metabolite using high-performance liquid chromatography. PMID- 4019695 TI - Microanalyses of beta-cyclodextrin in plasma by high-performance liquid chromatography. AB - Procedures for the micro-determination of beta-cyclodextrin (beta-CyD) in plasma were investigated by four methods using high-performance liquid chromatography (HPLC). In methods A and B, underivatized beta-CyD was detected with a refractive index detector and determined by the absolute calibration graph method. An NH2 bonded silica/acetonitrile-water system was used in A and a C18-bonded silica/methanol-water system in B. In method C, the percarbanilate of beta-CyD was separated on a C8-bonded silica column with acetonitrile-water and determined using gamma-CyD as the internal standard with a UV detector at 231 nm. In method D, the per[1-14C]acetate of beta-CyD was fractionated on a silica column with n hexane-ethanol containing 1% of water and the radioactivity of each fraction was measured with a liquid scintillation counter. gamma-CyD was used as the internal standard. Interfering plasma proteins were removed by centrifugal ultrafiltration with an MPS-1 micro-partition system. Method B was superior to the other methods with respect to ease of sample preparation, sensitivity and time required for analysis. The cumulative amount of beta-CyD in the mesenteric vein absorbed from the rat intestinal lumen after administration of phenobarbital-beta-CyD complex in a closed loop method was determined by the use of method B. PMID- 4019696 TI - Improvement of ion chromatography with ultraviolet photometric detection and comparison with conductivity detection for the determination of serum cations. AB - Studies were made of the analytical conditions required for indirect photometric ion chromatography using ultraviolet photometric detection (UV method) for the determination of serum cations following a previously developed serum pre treatment. The sensitivities of the conductivity detection (CD) and UV methods and the amounts of serum cations determined by both methods were compared. Attempts to improve the sensitivity of the conventional UV method are reported. It was found that the mobile phase previously reported by Small and Miller showed no quantitative response when more than 4 mM copper(II) sulphate pentahydrate was used. As a result, there was no significant difference in the amounts of serum cations shown by the CD and UV methods. However, by adding 0.5-5 mM cobalt(II) sulphate heptahydrate, nickel(II) sulphate hexahydrate, zinc(II) sulphate heptahydrate or cobalt(II) diammonium sulphate hexahydrate to 0.5-1.5 mM copper(II) sulphate pentahydrate, higher sensitivity and a quantitative response were attained. PMID- 4019697 TI - Quantitative determination of tramadol in human serum by gas chromatography-mass spectrometry. AB - A gas chromatographic-mass spectrometric method for the quantitative determination of tramadol in human serum, plasma or whole blood samples is described. The method involves the use of [2H2, 15N]tramadol hydrochloride as an internal standard and chemical ionization with isobutane, employing single-ion monitoring for quantification. It is specific, sensitive and precise, and has high accuracy. The within-run coefficient of variation is about 1% between 25 and 200 ng/ml and 1.8-2.9% at the lowest concentrations tested (6.25 and 12.5 ng/ml). The between-run coefficient of variation increases from 1.6% to 5.2% with decreasing concentration from 200 to 12.5 ng/ml. The calibration graphs were linear in the tested concentration range, and the accuracy of the assay was not dependent on the sample volume used. The detection limit was about 4 ng/ml for serum samples of 1 ml. The method proved suitable for pharmacokinetic studies. Its high sensitivity allows measurements of serum concentrations for at least 30 h after the single administration of therapeutic doses of tramadol hydrochloride. PMID- 4019698 TI - Use of dual-column fused-silica capillary gas chromatography in combination with detector response factors for analytical toxicology. AB - Retention and detector response factor data have been given for 188 compounds on the DB1 capillary column using a dual nitrogen--phosphorus and flame ionization detection system. Factors affecting the detector response factor parameter in a dual-capillary column system have been discussed showing its advantage in drug screening. PMID- 4019699 TI - High-performance liquid chromatographic determination of cicletanide, a new diuretic, in plasma, red blood cells, urine and saliva. AB - A sensitive, selective and easy to use high-performance liquid chromatographic method for the determination of cicletanide, a new diuretic, in plasma, red blood cells, urine and saliva is described. After extraction of cicletanide together with an internal standard with diethyl ether, or diethyl ether-n-hexane (20:80) for urine, the sample extracts are chromatographed with water-methanol-acetic acid (50:50:0.3) as eluent on to a Nucleosil C18 column. Both compounds are detected by their ultraviolet absorption at 280 nm. The calibration graph was linear between 0.2 and 20 micrograms/ml for plasma and between 0.2 and 5 micrograms/ml for the other biological fluids. The sensitivity limit was 20 ng/ml for plasma, red blood cells and saliva and 30 ng/ml for urine. The coefficients of variation of the between-day assays did not exceed 4.6% in plasma, 8.3% in red blood cells, 7.8% in urine and 4.2% in saliva for the lowest concentrations studied. The application of the method to a pharmacokinetic study of cicletanide after a single oral therapeutic dose in humans is reported. PMID- 4019700 TI - Physical characterization of PBCV virus by sedimentation field flow fractionation. AB - A virus (PBCV) from the symbiotic Chlorella-like algae of Paramecium bursaria has been characterized by sedimentation field flow fractionation (SdFFF). The method yields effective molecular weight M' (molecular weight X buoyancy factor) with a precision of better than 5% under a variety of experimental conditions. The value for M' is used to calculate true molecular weight values through combination with density values; densities were obtained from outside sources, from ultrasonic densitometry, and from sedimentation coefficients determined independently. The actual molecular weight is also determined through SdFFF analysis of the virus in carriers of different densities. Values for the particle diameter are obtained from SdFFF zone broadening studies. The various SdFFF characterization results are compared with molecular weight, particle size, and density values determined by conventional methods. PMID- 4019701 TI - Cardiovascular disease risk factors related to sexual maturation: the Oslo Youth Study. AB - This paper focuses on cardiovascular disease risk factors as they are influenced by sexual maturation. Serum total cholesterol, HDL-cholesterol, fasting triglycerides, blood pressure, height, weight and triceps skinfold thickness were investigated longitudinally in a population of 550 Norwegian adolescents aged 10 14 years at the onset. Two identical surveys were conducted, the first in 1979 and the last in 1981. Included in the study was a measure of developmental age, assessed by using sex maturity ratings formalized by Tanner. The physiological endpoints (except triglycerides) were more strongly related to developmental age than to age in years. Among 11 and 12 year old males, values not adjusted for sexual maturation stage underestimated height, weight and blood pressure and overestimated skinfold thickness, total cholesterol and HDL-cholesterol. In 15 and 16 year old males, unadjusted values overestimated height, weight and blood pressure, and underestimated total and HDL cholesterol. For females, unadjusted values underestimated height, weight, body mass index, triceps skinfold thickness and blood pressure among 11-12 year olds and overestimated the same variables for 15 and 16 year olds. These findings indicate that for adolescents, an index of physiological development more precise than chronological age should be included in epidemiological studies. PMID- 4019702 TI - Causes of death in Japanese diabetics. A 20-year study of death certificates. AB - Death certificates filed between 1960 and 1979 in Osaka, Japan were analyzed to study causes of death in diabetic patients. It was observed that diseases of the circulatory system increased continuously from 15.2% in 1960-1964 to 27.2% in 1975-1979. Cerebrovascular disease and disease of heart were the leading causes of death throughout the study period. The rate of increase was much faster for disease of heart than for cerebrovascular disease, and there was only a small difference between them as cause of death in diabetic patients at the end of the observation period. Malignant neoplasms, cirrhosis of the liver, and pneumonia and bronchitis increased, whereas tuberculosis decreased sharply according to age adjusted mortality rate during the 20-year period. Analysis based on O/E ratios suggested higher risk of dying from ischemic heart disease, tuberculosis and cirrhosis of the liver in Japanese diabetics than in the general population in this country. PMID- 4019703 TI - The use of polytomous dual response data to increase power in case-control studies: an application to the association between dietary fat and breast cancer. AB - Computer simulation has been used to compare various methods for analyzing data from case-control studies when two response variables are available to measure a risk factor. When such variables are continuous or polytomous, and a dose response relationship exists, it is concluded that power may be increased by including individuals who are discordant on their responses. Failure to use the most appropriate method can lead to a substantial loss in power. The results are illustrated by reanalysis of data from an earlier case-control study of diet and breast cancer. This reanalysis has strengthened the evidence for a positive association between saturated fat intake and risk of breast cancer, with some suggestion that this association is limited to premenopausal women, in whom the increase in risk may be substantial. PMID- 4019704 TI - Population risk of cardiovascular disease: the Minnesota Heart Survey. AB - A decline in age-adjusted ischemic cardiovascular disease mortality has been observed in the United States during the past two decades. Among the leading explanatory hypotheses is improvement in the major known risk factors for heart attack and stroke in the general population, specifically hypertension, smoking, and lipid levels. To better understand risk factor trends, the Minnesota Heart Survey (MHS) began systematic risk factor surveys of the Minneapolis-St Paul population in 1980, (population 1.99 million). The metropolitan area was divided into 704 subareas (clusters) of approx. 1000 households each, utilizing geographic boundaries. In a two-stage cluster sampling technique, 40 subareas were randomly chosen and mapped. Approximately 8.75% of households were chosen from each subarea and selected residents age 25-74 years invited to participate. A total 4451 individuals participated in 1980-82. The response rate for a home interview was 81.9 and 84.4% for a subsequent survey center visit, producing an overall response of 69.1%. The age and sociodemographic characteristics of the survey participants were similar to those found in the 1980 census. The prevalence of hypertension was 18.3% in this population with 76.0% taking medications and 65.0% controlled. Total cholesterol and HDL-cholesterol levels demonstrated age and sex differences similar to those reported elsewhere. Current smoking of cigarettes was equally prevalent in men (34.5%) and women (33.5%) although more men were former smokers (35.2 vs 20.6%). Comparison of the MHS with the National HANES II data (1976-80) indicates lower regular cigarette smoking among Minnesota males, with similar rates in females. Minnesota residents had better control of high blood pressure. PMID- 4019705 TI - Determining the duration of comparative clinical trials while allowing for cure. AB - Rubinstein et al. provide a technique for estimating the required length of accrual in a two treatment group randomized survival trial. An important parameter in this approach is the expected number of events as estimated by assuming exponential failure. When the underlying distribution of failure times displays a distinct plateau, as in many children's cancers (i.e. there is a "cure"), the assumption of exponential failure could be misleading. In this situation we propose the use of the general formulation in [1], but with the expected number of failures based on failure models with hazard functions which may decrease to zero. We suggest two such models and show that they provide a good fit in an example from Childrens Cancer Study Group (CCSG) trials, and that the determination of required trial duration depends strongly upon which model is assumed. PMID- 4019706 TI - Effects of pulmonary function on mortality. AB - Survivorship data from a 24 year longitudinal study of 874 male volunteers in the Baltimore Longitudinal Study of Aging were used to assess the role of pulmonary function on total mortality. Even when age and smoking were considered, the ratio of forced expiratory volume in 1 sec to its predicted value was significantly associated with mortality from all causes. Individuals with poorer pulmonary function showed greater mortality during the follow-up period of this study. This relationship was also seen among never smokers in this sample, further supporting the hypothesis that impaired pulmonary function is itself a predictor of total mortality and may contribute to a number of disease processes. PMID- 4019707 TI - Chronic schizophrenia and Alzheimer's disease. The losses for parents, spouses and children compared. PMID- 4019708 TI - CPR. PMID- 4019709 TI - Sample size: clues, hints or suggestions. PMID- 4019710 TI - Presence of a nonlactogenic factor in human serum which synergistically enhances prolactin-stimulated growth of Nb2 rat lymphoma cells in vitro. AB - A nonlactogenic factor(s) which synergistically enhanced the effect of ovine PRL in stimulating the growth of Nb2 rat lymphoma cells in suspension culture was found in human serum. The identity of the factor is unknown, but it is heat stable, with a mol wt apparently in excess of 8000 daltons. It possesses no growth-stimulating activity in the absence of PRL. Insulin acts in a similar manner to this factor in the Nb2 bioassay, suggesting that the factor may be somatomedin-like, possibly related to the previously described synlactin. PMID- 4019711 TI - Monoclonal antibody recognition of multiple forms of estrogen receptor tagged with [125I]methoxy-iodovinyl estradiol in ovarian carcinomas. AB - Based on previous studies of the properties of moxestrol, we hypothesized that a radiohalogenated analog of moxestrol, [125I]11 beta-methoxy-17 alpha-iodovinyl estradiol [( 125I] MIVE2), should bind to the estrogen receptor (ER) in some ovarian adenocarcinomas (OVCA), thereby offering the potential for imaging and/or treatment of these cancers. We used monoclonal antibodies (H222, H226, and D547) against human breast cancer ER to identify the [125I]MIVE2-binding moiety in OVCA cytosols that is found on high salt sucrose gradients. After gel electrophoresis and western blotting, exposure of OVCA extracts to the ER antibodies, followed by exposure to goat antirat serum and then rat peroxidase antiperoxidase, demonstrated a moiety in OVCA that migrated indistinguishably from the ER in MCF 7 human breast cancer cells and from that in specimens of breast cancer tissue. Because few studies have demonstrated efficacy of hormone management for OVCA, we also wanted to learn whether ER exists in multiple forms in OVCA, in view of the possibility that some forms may be inactive in regulating growth-dependent cell functions while retaining estrogen-binding capacity. By incubating the monoclonal antibodies H222, H226, and D547, each of which recognizes a different region on the ER protein, with OVCA cytosol fractions, we demonstrated that ER in OVCA can exist in multiple forms, some of which fail to express an H226-recognized site and some of which fail to express a D547-recognized site. This observation indicates that a relationship may exist between the presence or absence of certain forms of ER in ovarian epithelial cancer and a patient's response to hormone therapy. PMID- 4019712 TI - Age-related changes in the circadian rhythm of plasma cortisol in man. AB - We studied the effect of age on the circadian rhythm of plasma cortisol in 34 normal subjects, aged 18-75 yr. Blood was sampled at 20-min intervals beginning at 2000 h, and the data were analyzed using the PULSAR program and the cosinor method. There was a negative correlation between age and the time of the maximum cortisol concentration (r = -0.548; P = 0.001), the time of the nadir cortisol concentration (r = -0.543; P = 0.001), and the acrophase (r = 0.528; P = 0.001). When the subjects were divided into those 39 yr of age and younger and 40 yr of age and older, the times of the cortisol nadir, maximum, and acrophase were significantly earlier in the older group. The interval between the nadir and peak cortisol levels was not significantly different, consistent with an age-related phase advance of the cortisol circadian rhythm. Quantitative indices of adrenal function, including the 24-h mean cortisol concentration and the number of cortisol peaks as well as their amplitude and duration, were not different in the two groups. There was a significant negative correlation between age and customary bedtime (r = -0.686; P = 0.001) that may explain, in part, the phase advance in the older subjects. This observation strengthens the evidence that sleep onset is a major factor contributing to synchronization of the cortisol rhythm. Alternative explanations are that age-related changes in the control of hormonal and other rhythms have important influences on sleep and activity schedules, or that sleep and cortisol variables do not influence each other, but are both the final expression of some central change. PMID- 4019713 TI - Evidence for the existence of des-Asp1-angiotensin II in human uterine and adrenal tissues. AB - Renin is present in various tissues outside the kidney. In contrast, the levels of angiotensins (ANG), the active products of the renin-angiotensin system, have not been thoroughly evaluated in tissues. In this study, we demonstrated the presence of immunoreactive (ir) ANG I and ANG II in various human tissues by RIA. Of the tissues examined, uterine tissue contained the most ir-ANG II. Since the anti-ANG II antibody used had significant cross-reactivity with ANG III, high performance liquid chromatography was performed to separate ANG II from ANG III. The major portion of the ir-ANG II in the plasma was ANG II. In contrast, the major portion of the ir-ANG II in uterine tissue was determined to be ANG III, a known biologically active peptide. The adrenal gland and testis also contained ANG III. From these results, it can be postulated that ANG III may contribute to the biological activity of ANG in some tissues. PMID- 4019714 TI - Prospective serum thyroglobulin measurements in assessing the risk of developing thyroid nodules in patients exposed to childhood neck irradiation. AB - We examined 327 patients with a history of cervical radiation treatment for benign conditions and followed them for an average of 5.6 yr. These patients were selected because they initially had normal examinations and normal serum thyroglobulin levels. Of the 327 patients, 48 developed thyroid nodules, and an additional 30 had other clinical changes in their thyroids. Serum thyroglobulin increased by 4.0 +/- 0.6 (+/- SEM) ng/ml in those who remained normal, by 13.4 +/ 5.2 ng/ml in those who were no longer normal, and by 17.1 +/- 8.2 ng/ml in those who developed nodules. We conclude that increasing levels of serum thyroglobulin identify patients who should be examined and followed more carefully for thyroid nodules and thyroid cancer. PMID- 4019715 TI - Heterogeneity of fracture syndromes in postmenopausal women. AB - Studies were performed on 32 women with vertebral crush fractures (mean age, 65.1 yr) and 27 patients with recent hip fractures (mean age, 83.6 yr). Histomorphometric analysis of undecalcified transiliac crest biopsies revealed significant differences between the two fracture groups. Trabecular bone volume (TBV) was significantly lower in vertebral fracture than in hip fracture patients (12.0 +/- 4.4% (+/- SD) vs. 14.8 +/- 3.6%; P = 0.014), while thickness of cortices was significantly lower for hip fracture than for vertebral fracture patients (436 +/- 231 vs. 823 +/- 465 microns; P less than 0.001). The TBV and radial bone mass (measured by absorptiometry on the shaft) for the vertebral fracture group were significantly lower than age-expected values. For the patients with hip fractures, the TBV was significantly above the expected value, and radial bone mass was not significantly different from the expected value. Other quantitative histological measurements did not generally differ between the two fracture groups and were compatible with normal or increased bone remodeling. The serum PTH in the hip fracture group was significantly increased above that expected in normal women of similar age. These data demonstrate the anatomical heterogeneity of osteoporotic fracture syndromes. Patients with vertebral fractures have an early deficit of trabecular bone for their age, while those with hip fractures have a deficit of both cortical and trabecular bone compared to women of age 50 yr, but the deficit is not excessive compared to others of similar age without fractures. PMID- 4019716 TI - [Studies on side effects induced after inoculation with influenza vaccine. Groups of primary school children (between the ages of 6 and 13 years old) as subjects of study]. PMID- 4019717 TI - [A study on the causes of an epidemic of influenza, especially an analysis of relative humidity as a main cause]. PMID- 4019718 TI - Field adaptation in the horizontal cells. Rushtonian transformation. PMID- 4019719 TI - [Studies on the cellular immunological response in splenectomized or autotransplanted mice]. PMID- 4019720 TI - [Isolation and subcellular localization of a large molecular iron binding protein in rat intestinal mucosa]. PMID- 4019721 TI - [On social research in the field of public health]. PMID- 4019722 TI - [Modified criteria for diagnosis of Kawasaki disease]. PMID- 4019723 TI - [On death due to influenza]. PMID- 4019724 TI - [An occupational health survey on beauticians in Japan (II)]. PMID- 4019725 TI - An epidemiologic study on hepatitis B virus infection in Chiang Mai, 1983-1984. PMID- 4019726 TI - Cerebral blood flow and mental function in dementia. PMID- 4019727 TI - Genetic and developmental studies of a new mouse mutation that produces otocephaly. AB - A new recessive lethal mutation in mice that produces the otocephaly defect is described. The mutation, provisionally named oto is located on chromosome 1, within, or just outside of, a previously existing inversion, In(1)1Rk, and was probably induced by X-irradiation. The penetrance of oto is nearly complete on C57BL strain backgrounds but is reduced to a variable extent on other backgrounds. The previously reported liability to spontaneous otocephaly in the C57BL strains appears to increase the penetrance of oto. Studies of the sequences of developmental changes (conducted primarily by scanning electron microscopy) and of the range of defects indicate that a primary deficiency involving the anterior aspect of the embryonic disc occurs in affected individuals. An hypothesis related to deficiencies in mesodermal populations is presented as the basis for the craniofacial and brain defects observed. PMID- 4019728 TI - Temporomandibular malformations in the bonnet monkey (Macaca radiata) fetus following maternal ingestion of thalidomide. AB - Structural abnormalities of the temporomandibular region were seen and described in the fetal bonnet monkey (Macaca radiata) after maternal ingestion of thalidomide. A single oral dose of 10 mg/kg of thalidomide was given on day 24, 25, 26, 27, 28 or 29 or 30 mg/kg on day 25 or 28 of gestation to 25 pregnant monkeys (day of mating = 0). The skeletons, processed and stained with alizarin red S, were examined for gross changes in configuration of craniofacial bones. Temporomandibular defects, in varying severity, were seen in four 70-day-old and seven 100-day-old fetuses associated with a single treatment between day 24 and day 28. The highest risk appeared to occur following treatment on day 25 (4/5) and the lowest on day 28 (2/8). Characteristic expression of the defects included 1) temporo-zygomatic hyperplasia involving the articular tubercle and postglenoid process and 2) mandibular hypoplasia, primarily of the condyles and the angular and coronoid processes. Micrognathia, apertognathia, and partial extraarticular ankylosis were seen. Although the sensitivity periods of the temporomandibular and ear regions seem to overlap and the embryonic origins are similar, the defects of each region appeared to be independent. Although the ear demonstrated a definite temporal relationship characterized by a decrease in severity in the expression of the ear malformations with respect to increased gestational age at the time of thalidomide insult, the temporomandibular region failed to exhibit a specific pattern. Although the temporo-zygomatic hyperplasia was dissimilar to any reported human condition, the mandibular changes were similar. PMID- 4019729 TI - A preliminary study of mandibular shape. AB - There is a growing realization that traditional osteometric data are of uncertain scientific validity, primarily due to the lack of dissociation between size and shape parameters. This study was specifically based on the metrical definition of mandibular morphologic shape, using a technique termed medial axis transformation. It was based on the digitized mandibular outlines of three age sexed samples of microcephalics, macrocephalics, and normocephalics. Evaluation of the derived medial axis lengths and branch point distances indicated complex patterns of mandibular shape contrasts between microcephalics and macrocephalics on the one hand and normocephalics on the other. Although larger more homogeneous samples are required to evaluate the specific factors influencing mandibular shape, the present data suggest an association between mandibular shape and cranial form. PMID- 4019730 TI - Velopharyngeal variations in relatives of cleft-affected individuals. AB - Eighteen families each with two or more cleft lip and palate patients were studied by speech cephalometry for evidence of velopharyngeal inadequacy (VPI). With this total of 56 persons, three groups were recognized: 1) patients with cleft lip only (N = 7), 2) unaffected sibs of CL(P) probands and the unaffected parents with the positive clefting history on their side of the family (N = 33), and 3) unaffected parents with negative CL(P) history to their side of the family (N = 16). The latter served as controls. The velopharyngeal mechanism in function was evaluated by voicing the fricative/S/. The results showed no significant differences in the length of either the resting soft palate or pharyngeal depth among the three groups. Even though a significant (P less than 0.01) increase in soft palate length while voicing /S/ was found in group 2 relatives compared to group 3 controls, the failure to find differences in either resting palate length or pharyngeal depth coupled with a failure to demonstrate VPI in group 2 subjects by speech testing leaves the value of this observation uncertain. PMID- 4019731 TI - Male-to-male transmission of the velo-cardio-facial syndrome: a case report and review of 60 cases. AB - The velo-cardio-facial syndrome is one of the most common syndromes of clefting. Previous reports have shown vertical pedigree transmission, but in all cases the gene was maternally transmitted. The genetics of this syndrome had been suspected as autosomal dominant, but X-linked dominant inheritance could not be ruled out. This report describes an instance of male-to-male transmission of the velo-cardio facial syndrome. In addition, the clinical findings in 60 cases are reported to further delineate the phenotypic spectrum of the syndrome. PMID- 4019732 TI - Genetic analysis in families with van der Woude syndrome. AB - We have brought together information on 864 affected individuals in 164 families (including three new pedigrees) reported in the 137 year period since 1845 when Demarquay first described a family with what was later called van der Woude syndrome (VWS). Both types of oral cleft, cleft palate (CP) and cleft lip with or without CP (CLP), segregate in these families together with lower lip pits or fistulae in an autosomal dominant mode with high penetrance estimated to be K = .89 and .99 by different methods. Cleft types (CLP and CP) occur in VWS in the same proportions as in the general non-VWS population, ie, about twice as many cleft-bearing individuals have CLP as have CP. On the other hand, we do not find the usually observed excess of females with CP and excess of males with CLP; in VWS the sex ratios are more nearly equal. Lip pits also are equally distributed between the sexes. Affected males and females are equally likely to transmit VWS. However, there is an excess of less severely affected individuals among transmitters and a deficiency of more severely affected, brought about by a proband bias and differential fecundity. The expression of VWS is significantly modified by the genetic background: More extreme phenotypes in parents tend to produce more extreme expression in their children. For a VWS gene carrier the relative risk of transmitting a cleft is 26.45%; that of transmitting lower lip pits is 23.55%. Three pedigrees of lip pits in the literature show no clefts among a significant number of affected individuals. Control of gene expression in VWS in the three target tissues appears to be independent and separately designated. Mutation rate of the VWS gene is calculated to be 1.8 X 10(-5). PMID- 4019733 TI - Fate of recombinants of the rat mandibular epithelium with cranial ectomesenchymal cells of different sources in vitro. AB - The recombinants of the mandibular molar bud epithelia with cranial ectomesenchymal cell groups from several different sources--mandibular molar area, tongue anlagen, and lateral nasal process--were cultured. Dental laminalike buds were developed in each of the recombinants (incidence of development 38 86%). In the heterotrophic recombinants, heterotypic differentiation of mandibular epithelium was also induced. However, the foreign ectomesenchymal cells were not induced heterotypically by the epithelial genetic factor, but the mesenchymal genetic factor is maintained. It is suggested that mandibular molar bud epithelia have potency to proliferate into mesenchyme under non-organ specific influences of ectomesenchymal cells and that presumptive mandibular mucosal epithelia have multipotency for differentiation sensitive to inductive influences by the heterotypic cranial ectomesenchymal cells but that the mandibular molar bud epithelia have no heterotypic inductive activity for the differentiation of cranial ectomesenchymal cells. PMID- 4019734 TI - In vitro assessment of virulence in Yersinia enterocolitica and related species. AB - We have examined 136 isolates of Yersinia species, comprising 112 strains of Yersinia enterocolitica, 12 of Y. frederiksenii, 8 of Y. intermedia, and 5 of Y. kristensenii, for the presence of 40- to 50-megadalton virulence-associated plasmids and expression of the following plasmid-associated characteristics: Congo red pigmentation (CR), calcium dependence, autoagglutination, hydrophobicity, resistance to normal human serum, and pathogenicity in mice. All 136 strains yielded both pigmented (CR+) and nonpigmented (CR-) variants. Only CR+ variants, however, were virulent for iron-overloaded, desferrioxamine B treated mice (R. M. Robins-Browne and J. K. Prpic, Infect. Immun. 47:744-779, 1985). Although the in vitro virulence-associated characteristics generally occurred together, each one could be expressed independently. Strains of Y. frederiksenii, Y. intermedia, and Y. kristensenii also expressed individual virulence-associated properties. Of 53 Y. enterocolitica strains which were virulent for iron-overloaded, desferrioxamine-treated mice, all but one expressed every virulence-associated characteristic. Several strains which were avirulent for mice, however, demonstrated these characteristics in various combinations. Because many Yersinia strains, particularly environmental isolates, carried plasmids of 40 to 50 megadaltons, detection of plasmids provided little information about bacterial pathogenicity unless virulence-associated properties were also sought. The best in vitro predictor of virulence was autoagglutination, followed by calcium dependence. Because only CR+ variants expressed virulence associated determinants, Congo red pigmentation is useful for selecting potentially virulent strains. PMID- 4019735 TI - Evaluation of xylan fermentation for the identification of Bacteroides ovatus and Bacteroides thetaiotaomicron. AB - The reliability of xylan fermentation in distinguishing Bacteroides ovatus from Bacteroides thetaiotaomicron was examined with strains previously identified by DNA homology studies or bacteriophage sensitivity testing or both. All of the 12 B. ovatus strains produced acid ranging from pH 5.0 to 5.6 in peptone-yeast-xylan broth; none of the 19 B. thetaiotaomicron strains produced acid, and the final pH was 6.0 or 6.1. Xylan fermentation and bacteriophage sensitivity-DNA homology appear to be equivalent in their ability to differentiate these two Bacteroides species. PMID- 4019736 TI - Streptococcus pneumoniae type 16A, a hitherto undescribed pneumococcal type. AB - Some properties of a newly recognized pneumococcal capsular serotype, type 16A, are described, bringing the number of capsular types characterized to 84. PMID- 4019737 TI - Development of a bacteriophage typing system for Campylobacter jejuni and Campylobacter coli. AB - A bacteriophage typing system for Campylobacter jejuni and Campylobacter coli was developed with phages isolated from poultry feces. Data for phage selection were generated from a set of isolates of C. jejuni and C. coli from humans in Illinois. Selection of 14 phages from the 47 phages available was assisted by determination of the Sneath-Jaccard similarity coefficients and subsequent unweighted pair-group arithmetic averaging cluster analysis. The typing set was reproducible and stable in the 255 isolates from Illinois. Of these isolates, 94.5% were typable, with 46% represented by the four most common phage patterns. In a set of 51 isolates from humans outside of Illinois, 88.1% of the C. jejuni isolates were typable. Phage typing for C. jejuni and C. coli has excellent epidemiologic potential and should serve as a useful adjunct or alternative to serotyping systems in current use. PMID- 4019738 TI - Pseudodiffuse-type growth of a Staphylococcus aureus strain in serum-soft agar. AB - Strain MC31 of Staphylococcus aureus showed diffuse-type growth in regular serum soft agar (SSA) (pH 7.2), but in alkaline SSA (pH 8.4) the type of growth was compact. The organisms were of extra low virulence in the mouse and were unencapsulated. Based on three properties, the growth type of the S. aureus strains in SSA was designated as pseudodiffuse type. PMID- 4019739 TI - Clinical evaluation of the Lumac bioluminescence method for screening urine specimens. AB - A bioluminescence method for screening urine cultures to provide rapid reporting of negative specimens and to select appropriate urine cultures for direct application of automated identification methods was evaluated. A total of 2,000 specimens were processed in the Lumac Biocounter (3M, St. Paul, Minn.), and the results were compared with quantitative culture techniques by using a 0.001-ml inoculating loop. A total of 841 specimens were positive by the bioluminescence method; 291 specimens were culture positive (greater than or equal to 50,000 CFU of one or two organisms per ml). Positive cultures represented more than 20 different organisms. Approximately two-thirds of the false-positive results represented mixed flora or pure cultures of less than 5 X 10(4) organisms per ml. The predictive value of a negative result was 98.4%, reflecting a false-negative rate of only 0.7%. No advantages in cost or technician time were noted, but the Lumac method appears to be a useful technique in decreasing reporting time, especially for negative urine cultures. PMID- 4019740 TI - Mechanism of cross-contamination of blood culture bottles in outbreaks of pseudobacteremia associated with nonsterile blood collection tubes. AB - Several studies have identified nonsterile blood collection tubes as the reservoir for contaminating microorganisms in outbreaks of pseudobacteremia. Microorganisms are thought to be transferred from the nonsterile tubes to the blood culture tubes when blood is drawn for cultures, but the validity of this hypothesis has not previously been tested. We recently investigated an outbreak of Ewingella americana pseudobacteremia in which an epidemiological association was found between pseudobacteremia and the practice of drawing blood for culturing at the same time that blood for coagulation studies is drawn. The nonsterile coagulation tubes, prepared in the hospital, were contaminated with E. americana. We studied three different procedures that personnel reported using to inoculate blood culture tubes after dispensing blood into the coagulation tubes. Although the failure to change or remove the needle before inoculating the blood culture tubes resulted in the highest percentage of cross-contamination, we found that all the techniques we simulated carried some risk of cross-contamination when coagulation tubes were filled first. PMID- 4019741 TI - Invasiveness of Aeromonas spp. in relation to biotype, virulence factors, and clinical features. AB - Of 69 fecal isolates of Aeromonas spp., 18 had the ability to invade HEp-2 cells. Invasiveness correlated with biotype; of the 18 invasive strains, 16 were A. sobria and 2 were A. hydrophila. No invasive strains were found among the A. caviae. Of the 18 invasive strains, 13 were enterotoxigenic. Of the enterotoxigenic and invasive strains, 12 were A. sobria, but enterotoxicity was also more common among noninvasive strains of A. sobria. Fucose-resistant hemagglutination was also more common in A. sobria, but invasive strains were equally divided between fucose-resistant hemagglutination and other patterns. Detailed clinical information was available for 27 of the 69 strains. All 15 strains of A. sobria or A. hydrophila associated with diarrhea were enterotoxigenic; 6 of the 10 strains of A. sobria were also invasive. Blood was present in the stool samples of five of the six patients with invasive A. sobria and in none of the patients with noninvasive strains. Although limited, these observations suggest that dysenteric symptoms may be produced by invasive Aeromonas spp. PMID- 4019742 TI - Isolation medium for the recovery of Pseudomonas cepacia from respiratory secretions of patients with cystic fibrosis. AB - A new medium for the isolation of Pseudomonas cepacia from respiratory tract secretions of patients with cystic fibrosis (CF) is described. This medium consists of inorganic salts, 0.5% pyruvate, and 0.1% proteose peptone as nutritive components and 0.0001% crystal violet, 0.15% bile salts, 100 micrograms of ticarcillin per ml, and 300 U of polymyxin B per ml as selective agents. The medium, designated PC medium, supported superior growth of 38 of 50 stock isolates of P. cepacia after 48 h of incubation when compared with MacConkey agar (0 of 50). The medium completely inhibited the growth of 112 of 124 stock isolates of organisms commonly found in respiratory secretions of CF patients. Cultures were made on PC medium with respiratory secretions of 169 CF patients. P. cepacia was recovered from 35 patients with isolates on PC medium but from only 21 patients with isolates on MacConkey agar. Of 221 other potentially pathogenic isolates found in these specimens, only six (two Pseudomonas aeruginosa isolates, two molds, one yeast, and one Serratia marcescens isolate) grew on PC medium. PC medium should facilitate the recovery of P. cepacia from CF patients. PMID- 4019743 TI - Serogrouping of Bacteroides vulgatus by the agglutination test. AB - The agglutination technique was used to establish a serological classification scheme for Bacteroides vulgatus strains isolated from normal human feces and clinical specimens, especially from ulcerative colitis patients. Absorbed antisera to 10 strains of B. vulgatus were prepared. These 10 absorbed antisera were species specific. Of 90 B. vulgatus strains tested, 55 (61%) were agglutinated by one or more of these 10 absorbed antisera. A total of 27 serological patterns were grouped into 18 serogroups; 10 of these serogroups contained only one group component, whereas the other 8 serogroups were composed of more than one component. This serological classification could be used to study the epidemiology of this organism. PMID- 4019744 TI - Clinical evaluation of three rapid methods for the detection of significant bacteriuria. AB - Random urine specimens (848) were screened for significant bacteriuria by using the 30-min Lumac (3M, St. Paul, Minn.), the 2-min Bac-T-Screen (Marion Laboratories, Inc., Kansas City, Mo.), and the 13-h AutoMicrobic system (AMS) urine identification card (Vitek Systems, Inc., Hazelwood, Mo.). MacConkey and 5% sheep blood agar plates were inoculated with a 10(-4) dilution of urine and used for the reference method. Bac-T-Screen results were uninterpretable for 9.1% of the specimens owing to either urine sample pigmentation (5.3%) or clogging of the filter (3.8%). Screen-negative urine specimens made up 49.6, 57.2, and 48.5% of the total number of specimens evaluated with AMS, Lumac, and Bac-T-Screen, respectively. False-positive results with Lumac and Bac-T-Screen were 20.6 and 22.3%, respectively. False-negative results for cultures with greater than or equal to 10(4) CFU/ml were 22.0% with AMS, 29.4% with Lumac, and 25.5% with Bac-T Screen, and false-negative results for cultures with greater than or equal to 10(5) CFU/ml were 29.6% with AMS, 9.9% with Lumac, and 7.0% with Bac-T-Screen. For each system, greater than 70% of false-negatives at greater than or equal to 10(5) CFU/ml consisted of mixed or pure cultures of common contaminants. With any of these screening methods, a clinically significant isolate at greater than or equal to 10(5) CFU/ml would rarely be missed (less than or equal to 1.7% for all systems). A cost-effective and rapid approach to urine microbiology could consist of screening out negative specimens by either Lumac or Bac-T-Screen and processing only screen-positive specimens by the AMS. PMID- 4019745 TI - Fine-needle aspiration biopsy in diagnosis of soft tissue infections. AB - This study explores the efficacy of fine-needle tissue aspiration biopsy in the diagnosis of soft tissue infections that cannot be sampled satisfactorily by regular microbiological techniques. Aspiration biopsy was performed on 50 patients with presumptive soft tissue infections. The conditions investigated were decubitus, diabetic, ischemic, venous, and traumatic ulcers (2, 6, 1, 2, and 7 patients, respectively), cellulitis (23 patients), chronic osteomyelitis (5 patients), and infected surgical wounds (4 patients). Where possible, comparison with superficial cultures was made. All of the cultures obtained from aspirate samples taken from ulcers, chronic osteomyelitis, and infected surgical wounds were positive. In cellulitis, cultures from aspirates were positive in 30 and 81% of the cases, respectively, depending on the presence or absence of concomitant antimicrobial therapy. These results suggest that fine-needle deep tissue aspiration biopsy is reliable and clinically applicable for deep tissue sample collection. The procedure is simple, brief, and does not cause significant discomfort to the patient. It also plays an important role in providing a guideline for antimicrobial therapy. PMID- 4019746 TI - Immunocytochemical demonstration of glial-neuronal interactions and myelinogenesis in subcultures of rat brain cells. AB - Subcultures have been established from primary rat brain cell cultures and have been characterised with a range of cell-specific immunocytochemical markers. The subcultures are mainly composed of fibrous astrocytes, oligodendrocytes and neurones. The cells do not divide to any great extent giving a system where it is possible to follow culture development at the cellular level for a number of weeks. During this time oligodendrocytes colonise subpopulations of neurones, differentiate further showing the presence of myelin basic protein and elaborate myelin-like membrane; the fibrous astrocytes remain scattered uniformly throughout the cultures. Radially oriented processes emerge from the oligodendrocyte-neurone aggregates which subsequently coalesce to form fascicles that link the clusters of cells together. These fascicles react with antibodies for both neurofilament protein and myelin basic protein. The subcultures provide a straightforward system that is composed of cells derived entirely from the CNS, is free from mitotic inhibitors and yet retains a sufficiently low cell density to allow immunocytochemical identification of the cell types present. The subcultures should be useful for the study of trophic interactions between oligodendrocytes and neurones as well as the early events associated with myelinogenesis. PMID- 4019747 TI - Comparison of three immunoassays in the screening and characterization of monoclonal antibodies against arginine-vasopressin. AB - A method for screening monoclonal antibodies (McAbs) to neuropeptides was evaluated using 8-arginine-vasopressin (AVP) as a model. Mice were immunized with AVP-thyroglobulin conjugate and their spleen cells were fused with X 63-Ag8.653 mouse myeloma cells. The resulting hybridoma supernatants were screened for specific antibody production using 3 different assays: solid phase enzyme radioimmunoassay in Terasaki plates (Ter-ELISA), liquid phase radioimmunoassay (LPRIA) and an immunohistochemical technique. From 2 independent fusions, 7 McAbs specific for AVP were obtained. They belonged to the IgG1 subclass and reacted more strongly to the ring part of the nonapeptide. The screening strategy proposed relies upon a crude selection of conjugate-reacting hybridomas, followed by neuropeptide-specific hybridoma identification using both LPRIA (with radioiodinated synthetic peptide) and an immunohistochemical technique (to detect natural neuropeptide). During subcloning steps Ter-ELISA is then chosen, to select for specific clones and to eliminate those reacting with the carrier thyroglobulin. PMID- 4019748 TI - The main immunogenic region of acetylcholine receptors does not provoke the formation of antibodies of a predominant idiotype. AB - Anti-idiotype antibodies were induced in rats by immunization with rat monoclonal antibodies to the main immunogenic region of acetylcholine receptors. These anti idiotype antibodies showed very little crossreaction with other rat monoclonal antibodies which bind to the same region of the receptor. When the rats producing these anti-idiotype antibodies were immunized with receptor, they showed no net decrease in anti-receptor antibody production. These data indicate that, although more than half of the antibodies produced by rats immunized with receptor are directed at a small region, many anti-receptor idiotypes are involved in this response and anti-idiotype therapy is not beneficial. PMID- 4019749 TI - Antibody response of rabbits to nerve ending gangliosides. Analysis of antibody specificity by liposome lysis and lysis inhibition assays. AB - Rabbits were immunized with nerve ending fraction prepared from guinea pig brain. Serum antibodies to total gangliosides were followed by enzyme-linked immunosorbent assay; their titers were highest at 2 to 3 weeks after immunization and some rabbits showed a response to reinjections. Specific reactivities of the antibodies against each molecular species of gangliosides were analyzed by liposome lysis assay and liposome lysis inhibition assay. Antibody responses were detected against GM1, GD1b, GM3 and GM2, but not against GD1a and GT1b. Natural and immune antibodies to the asialo glycolipids and to galactosylceramide were also observed. PMID- 4019750 TI - Spinal surgery in spinal muscular atrophy. AB - Fifteen patients with surgical treatment of spinal muscular atrophy were reviewed. The curve pattern was thoracic in 3, thoracolumbar in 11, and double thoracic and thoracolumbar in 1. Follow-up averaged 31 months. Eleven patients underwent posterior spinal fusion with Harrington instrumentation, with segmental wiring in four, and two had Luque instrumentation. The average age at time of surgery was 14.4 years. The average curve correction was 48%; that with the pelvic obliquity corrected, 63%. Surgery is best done when the curve is approximately 50-60 degrees, and Luque sublaminar wiring of Harrington or Luque rods with no external support appears to be the procedure of choice. PMID- 4019751 TI - The intrinsic vasculature of developing vertebral end plates and its nutritive significance to the intervertebral discs. AB - The structure and anatomical relationships of cartilage canals in the developing vertebral endplates of rabbits and humans are described in this study. In newborn rabbits, we observed a similar morphology and topologic arrangement to that in human fetal spines. Each vascular organ consisted of an arteriole, a glomerular tuft of sinusoidal capillaries, recurrent venules, and supporting loose connective tissue. Because the canals terminate adjacent to the intervertebral discs, they may provide an important source of nutrition to the disc during development when it is sandwiched between two layers of thick hyaline cartilage and contains no intrinsic vascular supply. PMID- 4019752 TI - Surgical fusion in childhood spondylolisthesis. AB - Twenty cases of surgical fusion for spondylolisthesis were reviewed at the Scottish Rite Hospital (Atlanta, GA, U.S.A.) to determine whether a procedure other than a simple posterolateral fusion is necessary for most patients. The patients were treated postoperatively with pantaloon spica cast immobilization. The fusion rate was high (90%), and patient satisfaction was high. One patient developed neurologic loss postoperatively. Two patients' slips progressed greater than 10% before solid fusion occurred. Thus, bilateral posterolateral fusion, followed by pantaloon spica cast immobilization, is effective for patients with symptomatic spondylolisthesis or asymptomatic children with grade 3 or greater slips. Reduction was not performed in this series. PMID- 4019753 TI - Acetabular hypertrophy in Legg-Calve-Perthes disease. AB - Measurements from the radiographs of 65 children with unilateral Legg-Calve Perthes disease showed that in 61 cases, the acetabulum was larger on the affected side by a mean of 4.0 mm. The mean femoral head size was increased in 60 of 65 cases by 6.8 mm. Acetabular and femoral head overgrowth occurred in a parallel fashion with onset early in the course of the disease. Hyperemia is the most likely explanation for this joint overgrowth. Acetabular contour was evaluated in 83 hips. Nineteen of these hips exhibited the sign of acetabular bicompartmentalization. This appears to be the result of maximally active cartilage hypertrophy and lateral placement of the femoral head. Bicompartmentalization can be seen 3 months after the onset of symptoms and is a poor prognostic sign. PMID- 4019754 TI - Value of the head-at-risk concept in assessing the prognosis in Legg-Calve Perthes disease. AB - Seventy-five hips affected by Legg-Calve-Perthes disease were reviewed. Three therapeutic groups were defined: conservative treatment, marrow emptying of the femoral neck, and varus derotation femoral osteotomy. Results were analyzed according to head-at-risk concept. Patients with head not at risk had better results regardless of treatment. Results in other groups were worse, but improved significantly with varus derotation femoral osteotomy. In children greater than 9 years of age, the results were almost invariably poor, irrespective of head-at risk designation. PMID- 4019755 TI - 10-year follow-up of split anterior tibial tendon transfer in cerebral palsied patients with spastic equinovarus deformity. AB - Split anterior tibial tendon transfer was performed on 21 patients (27 feet) with cerebral palsy and spastic equinovarus deformity. All patients required orthoses preoperatively. All but two patients are now community ambulators with improved gait and without need for orthoses. There was one recurrence of deformity. PMID- 4019756 TI - The value of computed tomography in the early assessment of comminuted fractures of the calcaneus: a review of three patients. AB - Computed tomography (CT) was performed within 4-8 days of injury in three patients with five fractures of the calcaneus. Three of the fractures were comminuted, and CT gave graphic additional information to the plain radiographs. Three fractures were undisplaced and were managed conservatively. In the other two, there was displacement of bony fragments, and these were treated operatively. In these, CT gave valuable preoperative information regarding the size and location of fracture fragments and helped the surgeon determine the site of incision and type of surgery required. The CT findings were confirmed at operation. CT therefore provides useful information for the management of these difficult fractures. PMID- 4019757 TI - Butler arthroplasty for correction of the adducted fifth toe: a retrospective study of 36 operations between 1968 and 1982. AB - This is a retrospective study of 30 children and adolescents who have undergone Butler arthroplasty for correction of an overriding fifth toe. Bilateral operations were performed on six patients, giving a total of 36 operations. Good to excellent results were obtained in 34 of the 36 operations. With attention to detail, this is a simple and safe operation. Full correction is obtainable without postoperative splintage or cast immobilization. This study represents the only reported experience in North America of this little-known procedure. PMID- 4019758 TI - The Grice extraarticular subtalar arthrodesis: a clinical review. AB - One hundred forty-nine Grice procedures performed between 1955 and 1982 were reviewed. The valgus deformities were secondary to poliomyelitis, cerebral palsy, myelodysplasia, flexible flatfoot, clubfoot, congenital vertical talus, and other neuromuscular diseases. Review consisted of radiographic and clinical follow-up. Overall evaluation revealed 46% unsatisfactory results because of both graft failure and residual clinical deformity. Previous unrecognized ankle valgus and instability prejudiced the results in the myelodysplasia and flexible flatfoot. Recommendations include consideration of the Grice procedure in poliomyelitis and cerebral palsy coupled with appropriate tendon balancing, but not in myelodysplasia or flexible flatfoot in the presence of often unrecognized ankle valgus. PMID- 4019759 TI - Polydactyly of the foot. AB - One hundred twenty-five patients with 194 supernumerary toes were analyzed. Postaxial polydactyly accounted for 79%. Duplication at the proximal phalanx with either a block metatarsal or a wide metatarsal head was the most common anatomical pattern. Sixty-one patients with 97 duplications evaluated at an average follow-up of 15.1 years postoperatively had 94% excellent or good results. Poor results were often associated with preaxial duplications and persistent hallux varus. Patients with central duplications often had a persistently wide forefoot. Surgical treatment is usually straightforward, but must be individualized. Preoperative radiologic assessment is mandatory. Certain technical considerations are related to better results. PMID- 4019760 TI - Radiographic measurement of infantile tibia vara. AB - The reproducibility of the radiographic measurement of 30 pairs of tibiae being treated for bowing was evaluated. Two methods of measurement were used. The first was the metaphyseal-diaphyseal angle of Levine and Drennan; the second, a metaphyseal-metaphyseal angle based on Cobb's angle for measuring scoliosis. Statistical analysis comparing the two methods showed no significant differences except for an increase in the angle in more severe cases measured by the metaphyseal-metaphyseal method, indicating distal tibial as well as proximal involvement. Computer digitization correlated extremely well with manual measurements. The metaphyseal-diaphyseal measurement is quite reproducible, and may allow early diagnosis and treatment of tibia vara. PMID- 4019761 TI - Consequences of an osteogenesis imperfecta diagnosis for survival and ambulation. AB - In osteogenesis imperfecta, time of initial fracture and radiographic appearance of long bones and ribs at time of initial fracture provide good prognostic indicators concerning survival and ambulation. Osteogenesis imperfecta congenita (OIC) comprises those patients with intrauterine and/or birth fractures. Radiographs of newborns with OIC-A show short, broad, and crumpled femurs and ribs, whereas initial radiographs of patients with OIC-B demonstrate bones with normal contours in spite of fractures. Osteogenesis imperfecta tarda (OIT) comprises those patients who fracture initially after birth. Patients with OIT-A fracture initially before walking begins, and patients with OIT-B after walking has begun. In OIC-A, 15 of 16 (94%) died; one survived but was wheelchair bound. In OIC-B, only two of 27 (8%) died, with 59% in wheelchairs and 33% ambulatory. No patients with OIT died. In OIT-A, 33% were in wheelchairs and 67% were ambulatory. In OIT-B, 100% were ambulatory. PMID- 4019762 TI - Acute calcium deposit in the hand of an 11-year-old girl. AB - A case of acute calcific deposit in the hand of an 11-year-old girl is presented. This is the first report of this entity in a child. The orthopedic surgeon and pediatrician are alerted to its existence and occurrence in the pediatric population. PMID- 4019763 TI - Segmental femur loss in children. AB - Two children with segmental femoral shaft loss were treated by skeletal traction to maintain soft tissue length, followed by casting to allow the callus to solidify. Initial traction was used to preserve length and allow for the development of bridging callus. Callus formation in 3-6 weeks was a good indicator for sufficient remaining periosteal sleeve to support healing without the need for bone grafting or internal fixation. These cases demonstrate the regenerative ability of the periosteum in healing pediatric fractures. PMID- 4019764 TI - Combined occipitoatlantoaxial hypermobility with anterior and posterior arch defects of the atlas in Pierre-Robin syndrome. AB - Combined occipitoatlantoaxial instability of the cervical spine occurred in a 8 year-3-month old boy with Pierre-Robin syndrome. He also had failure of ossification of both the anterior and posterior arches of the atlas. An in situ fusion from the occiput to C2 restored cervical spine stability. This case is discussed in relation to other hypermobility and instability syndromes of the cervical spine. PMID- 4019765 TI - Successful autogenous corticocancellous grafting of a radial defect complicating acute hematogenous osteomyelitis in an infant. AB - Recurrent osteomyelitis of the radius during infancy after initial hematogenous onset is rare. When encountered, this lesion may result in a segmental defect associated with limitation of forearm motion and progressive deformity. A 10 month-old girl developed distal radial osteomyelitis following bilateral otitis media. A radial defect developed and was treated successfully with autogenous tibial corticocancellous grafting. The surgical management of radial shaft defects is reviewed. PMID- 4019766 TI - Femoral neck fracture in a child with autosomal dominant osteopetrosis. AB - A child with autosomal dominant osteopetrosis had successful treatment of a femoral neck fracture by internal fixation. Drilling the pins into the femoral neck was extremely difficult. The histopathology in osteopetrotic bone provides a probable explanation for the technical difficulty seen in this case. PMID- 4019767 TI - Traumatic arterial spasm resulting in gangrene. AB - A fracture of the tibia in a child resulted in diffuse arterial spasm and ultimately gangrene. No evidence of a specific arterial injury was found. The role of spasm alone in the production of gangrene has been controversial. The case presented underscores its occurrence in the pediatric population and its potential consequences. Loss of limb can occur despite prompt recognition and treatment. A review of therapeutic options is presented. PMID- 4019768 TI - Partial aplasia of the pectoralis major muscle with an anomalous distal insertion: two case reports. AB - Two rare cases of subtotal aplasia of the pectoralis major muscle, a residual anomalous formation inserted abnormally into the medial humeral condyle, are discussed. PMID- 4019769 TI - "Sarah Kubitschek" Rehabilitation Center. PMID- 4019770 TI - Birth palsy: natural recovery course and combined root avulsion. PMID- 4019771 TI - Control of sodium and potassium transport in the cortical collecting duct of the rat. Effects of bradykinin, vasopressin, and deoxycorticosterone. AB - Several factors interact to maintain precise control of electrolyte transport in the mammalian cortical collecting duct. We have studied the effects of deoxycorticosterone, arginine vasopressin, and bradykinin on net transepithelial sodium and potassium transport in isolated, perfused rat cortical collecting ducts. Chronic administration of deoxycorticosterone to rats increased both sodium absorption and potassium secretion above very low basal levels. Consequently, deoxycorticosterone-treated rats were used for all remaining studies. Arginine vasopressin (10(-10) M in the bath) caused a sustained fourfold increase in net sodium absorption and a sustained threefold increase in net potassium secretion. Bradykinin (10(-9) M in the bath) caused a reversible 40-50% inhibition of net sodium absorption without affecting net potassium transport or the transepithelial potential difference. In the perfusate, up to 10(-6) M bradykinin had no effect. We conclude: As in rabbits, chronic deoxycorticosterone administration to rats increases sodium absorption and potassium secretion in cortical collecting ducts perfused in vitro. Arginine vasopressin causes a reversible increase in net potassium secretion and net sodium absorption. Bradykinin in the peritubular bathing solution reversibly inhibits net sodium absorption, possibly by affecting an electroneutral sodium transport pathway. PMID- 4019772 TI - Platelet-derived growth factor enhances in vitro erythropoiesis via stimulation of mesenchymal cells. AB - The growth of erythroid colonies (from erythroid colony-forming cells) and erythroid bursts (from burst-forming cells [BFU-E]) is enhanced in the presence of serum as compared with plasma. A significant proportion of the enhanced growth is due to the platelet release product, platelet-derived growth factor (PDGF). Colony growth in cultures of whole marrow cells in platelet-poor plasma-derived serum (PDS) and erythropoietin was enhanced in a dose-dependent fashion by increasing concentrations of purified human PDGF with optimal enhancement at 12.5 ng/ml. However, no effect of platelet-release products or PDGF was observed on nonadherent human marrow cells or peripheral blood BFU-E, suggesting that an accessory cell population was required for the effect of PDGF on hematopoietic progenitors. In a two-layer culture system, pure populations of fibroblasts or smooth muscle cells, known to be present in the marrow microenvironment, restored the response of nonadherent marrow cells in the overlayer to PDGF and also conferred responsiveness to peripheral blood BFU-E. Endothelial cells in the two layer culture system and macrophages, in contrast, lacked the ability to restore the enhancing effect of PDGF. Because other platelet-release mitogenic products are also found in serum, a monospecific anti-PDGF IgG preparation was added to cultures grown in platelet rich plasma-derived serum. Only partial reduction in colony and burst growth was seen, suggesting that other platelet-release products were acting in this system. These results demonstrate that PDGF enhancement of human hematopoietic progenitor cell growth requires mesenchymal cells, and provide an example and mechanism by which growth factors may influence hematopoietic progenitors via cells of the marrow microenvironment. PMID- 4019773 TI - Human fibronectin metabolism. AB - The metabolic behavior of fibronectin (Fn), a highly adhesive glycoprotein (440,000 mol wt), was studied in eight healthy control subjects and in 11 patients, six of whom were critically ill. Fn was purified from fresh human plasma, radiolabeled, and shown to retain function both in vitro and in vivo. Results showed that, in normal controls, Fn is a rapidly catabolized protein with a fractional catabolic rate (FCR) of 4.81%/h (range, 4.00-6.27), a half-life (t1/2) of 25 h (20-30), extravascular/intravascular diffusion ratio (EV/IV) of 2.04 (1.52-3.30), and a synthesis rate (SR) of 0.71 mg/kg body weight per h (0.61 0.87). There was evidence for extravascular catabolism in each subject. Plasma levels correlated with SR but not with t1/2 or FCR. Patients had a lower EV/IV ratio, and in two critically ill patients with low plasma Fn concentration the SR was markedly depressed. These findings suggest that reduced synthesis of Fn, rather than increased FCR or increased extravascular distribution, is responsible for Fn deficiency in critically ill patients. PMID- 4019774 TI - Measurement of regional neuronal removal of norepinephrine in man. AB - We describe here and validate an in vivo technique to measure the regional proportionate removal of norepinephrine (NE) by neuronal uptake (Uptake1) in man. The measurement is based on the steady-state arterial and venous concentrations of tritiated NE and tritiated isoproterenol (ISO) during simultaneous infusion of both. The validity of this technique depends on the removal of circulating NE, but not of ISO, by sympathetic nerve endings and on there being no other factor contributing to the net difference in the plasma disappearance of these catecholamines. To test these hypotheses, we compared the removal of NE in the arm with that of ISO in 14 people and the effects of pretreatment with the specific inhibitor of Uptake1, desipramine, in 8 people. In all the subjects a greater percent of NE than of ISO was removed during passage of blood through the forearm (54 vs. 46%, P less than 0.0001). Pretreatment with desipramine decreased significantly the removal of NE to virtually exactly that of ISO. The difference in NE and ISO clearances by arm tissues was therefore completely accounted for by Uptake1. About 15% of infused NE which is removed in the arm is removed by Uptake1. The ability to measure regional Uptake1 should contribute to better understanding of the relationship between circulating levels of plasma NE and sympathetic neural activity and may allow detection of abnormalities of neuronal norepinephrine removal in clinical disease states. PMID- 4019775 TI - Evidence for the presence of xenopsin-related peptide(s) in the gastric mucosa of mammals. AB - Using immunohistochemistry and radioimmunoassay, substance(s) related to the amphibian octapeptide xenopsin (XP) were demonstrated in the gastric mucosa of humans and dogs. Immunohistochemistry localized XP-immunoreactive epithelial cells in the gastric antral mucosa. The reaction was abolished by preabsorption of the antiserum with XP but not by neurotensin or other peptides. Immunoreactive XP (iXP) was found by radioimmunoassay in extracts of both the antrum and body of the stomach prepared with acid/acetone or acetic acid. A study of its distribution in the dog indicated that the level of iXP was highest in the stomach, lower in the pancreas and duodenum, and not measurable in the jejunoileum and colon. Gel chromatography on Sephadex G-25 indicated the presence of at least two forms of iXP, one larger and the other about the same size as XP. Reverse-phase high pressure liquid chromatography on mu-Bondapak C-18 yielded several peaks of iXP, one of which eluted at the position of synthetic XP. The results of immunochemical analyses using four different antisera towards XP were consistent with structures for canine iXPs that were closely related to XP only in their C-terminal regions. These results suggest that mammalian counterparts to amphibian XP reside within endocrine cells of the gastric mucosa. It seems possible that these peptides function as gastrointestinal signals. PMID- 4019776 TI - Plasma immunoreactive gamma melanotropin in patients with idiopathic hyperaldosteronism, aldosterone-producing adenomas, and essential hypertension. AB - A non-ACTH aldosterone-stimulating factor(s) has been implicated in the pathogenesis of idiopathic hyperaldosteronism (IHA). Although this factor has not been fully characterized, some evidence suggests that it may be related to a pro gamma-melanotropin (pro-gamma-MSH), derived from the NH2-terminal region of pro opiomelanocortin. In the present study, plasma immunoreactive (IR-) gamma-MSH levels at 0800 h in patients with IHA were evaluated (90 +/- 17 fmol/ml; range: 13-173 fmol/ml) and found to be significantly higher (P less than 0.05) than those in subjects with aldosterone-producing adenomas (33 +/- 8 fmol/ml), essential hypertension (33 +/- 6 fmol/ml), and normotensive controls (19 +/- 2 fmol/ml). Seven of nine IHA subjects had circulating IR-gamma-MSH levels above the normal range (greater than 35 fmol/ml). In plasmas sampled at 1200 h, IR gamma-MSH was significantly higher in patients with IHA (95 +/- 26 fmol/ml) and adenomas (63 +/- 23 fmol/ml), as compared with essential hypertensives (31 +/- 6 fmol/ml) and normotensives (19 +/- 3 fmol/ml). Mean plasma IR-ACTH, plasma cortisol, and urinary cortisol levels did not differ significantly between any of these groups. In order to evaluate the effect of a pro-gamma-MSH in vitro, adrenal adenoma tissue was obtained from two patients, one with elevated IR-gamma MSH (61 fmol/ml) and a second with low IR-gamma-MSH (12 fmol/ml). Aldosterone secretion by dispersed adenoma cells from the former, but not the latter, underwent a fourfold dose-dependent (10(-14)-10(-9) M) increase in response to human Lys-gamma 3-MSH. These data suggest that a pro-gamma-MSH may be implicated as a pathogenic factor in a subset of patients with primary aldosteronism, particularly among those differentially diagnosed as having IHA. PMID- 4019777 TI - Autoantibody to the C3b/C4b receptor and absence of this receptor from erythrocytes of a patient with systemic lupus erythematosus. AB - A 29-yr-old woman with systemic lupus erythematosus (SLE) was found to have no detectable C3b/C4b receptors (CR1) on her erythrocytes (E) when they were assayed by the binding of rabbit polyclonal and murine monoclonal (Yz-1) anti-CR1. Analysis by two-color fluorescent flow cytometry of CR1 expression on the patient's B lymphocytes that had been stained indirectly with monoclonal anti-B1 and rabbit F(ab')2 anti-CR1 also revealed a marked deficiency of CR1. Total cellular CR1 of neutrophils, assessed by a sandwich radioimmunoassay, was about half that of neutrophils from normal individuals. Because her E had expressed 173 sites/cell 2 yr before, the CR1 deficiency was considered to be acquired and a possible mechanism was sought. Autoantibody to CR1 was measured by a radioimmunoassay in which serum or its fractions were incubated in microtiter wells that had been coated with purified CR1, and binding of immunoglobulin to the wells was quantitated with 125I-labeled goat IgG antihuman F(ab')2. The CR1 specific binding of immunoglobulin from the patient's serum was 19.1 ng/well of the detecting antibody when her E had eight CR1 sites per cell; that of 28 healthy donors was 1.3 +/- 0.5 ng/well (mean +/- SEM), and that of 34 additional patients with SLE was 0.5 +/- 0.3 ng/well. The activity was present also in purified IgG and its F(ab')2 fragment, indicating that the binding of serum immunoglobulin to CR1 was not mediated by C3 fragments. The specificity of the patient's IgG for CR1 was confirmed when pretreatment of the CR1-coated wells with affinity-purified rabbit F(ab')2 anti-CR1 was shown to inhibit by 68% the binding of the IgG. The autoantibody also interacted with CR1 in cell membranes, as assessed by its capacity to inhibit the binding of indirectly fluoresceinated Yz-1 to neutrophils, and, when combined with goat IgG antihuman F(ab')2, to diminish the binding of dimeric C3b to normal E. During the period of the marked deficiency of CR1 the patient experienced an exacerbation of disease activity which was treated with prednisone. Clinical improvement was accompanied by a decrease in the serum concentration of anti-CR1 to levels present 2 yr earlier, and an increase of CR1 to 170 sites/E. The temporal association between high titers of an autoantibody to CR1, absence of CR1 from E, and heightened activity of SLE suggest that the former may have had a role in the other manifestations of the patient's disease. PMID- 4019778 TI - Influx of kininogens into nasal secretions after antigen challenge of allergic individuals. AB - We have recently demonstrated that kinins are generated in vivo after nasal challenge with antigen of allergic, but not nonallergic, individuals. The present study was undertaken as a first step in determining the mechanism(s) of kinin formation during the allergic reaction and was directed towards establishing the availability and origin of kininogens in nasal secretions. Allergic individuals (n = 6) and nonallergic controls (n = 5) were challenged with antigen; and by using specific radioimmunoassays, nasal washes, obtained before and after challenge, were assayed for high molecular weight kininogen (HMWK), total kininogen (TK), albumin, and kinins. Dramatic increases in HMWK (1,730 +/- 510 ng/ml), TK (3,810 +/- 1035 ng/ml), kinin (9.46 +/- 1.75 ng/ml), and albumin (0.85 +/- 0.2 mg/ml) were observed after challenge of allergic individuals which correlated (P less than 0.001) with increases in histamine and N-alpha-tosyl-L arginine methyl esterase activity and with the onset of clinical symptoms. For nonallergic individuals, levels of kininogens, albumin, and all mediators after antigen challenge were not different from base line. Linear regression analysis revealed excellent correlations (P less than 0.001 in each case) between increases in HMWK, TK, kinin, and albumin during antigen titration experiments and between the time courses of appearance and disappearance of HMWK, TK, kinin, and albumin after antigen challenge. Gel filtration revealed no evidence of degradation products of kininogens in nasal washes. For each allergic individual the ratio of HMWK/TK in postchallenge nasal washes was similar to the ratio of these two proteins in the same individual's plasma. These data suggest that, during the allergic reaction, there is an increase in vascular permeability and a transudation of kininogens from plasma into nasal secretions, where they can provide substrate for kinin-forming enzymes. PMID- 4019779 TI - Cationization of catalase, peroxidase, and superoxide dismutase. Effect of improved intraarticular retention on experimental arthritis in mice. AB - Several enzymes and other proteins were made cationic either by coupling to polylysine or by shielding of anionic sites. These cationic proteins, all having an isoelectric point greater than 8.5 exhibited excellent retention in articular structures when injected in mouse knee joints. Autoradiography and histochemistry showed that cationic forms of catalase, superoxide dismutase, and horseradish peroxidase were firmly retained by synovial and cartilaginous tissues. The half life of these enzymes in the joint is thus significantly extended compared with native enzymes. The native enzymes and their cationic derivatives were tested for antiinflammatory properties in mice, using antigen-induced arthritis and zymosan induced arthritis. It was found that injection of cationic catalase or peroxidase induced a marked suppression of some parameters of the inflammatory response in both types of arthritis, as measured by 99m technetium pertechnetate uptake and leakage of 125I-labeled albumin. Native catalase and peroxidase were less, or not at all effective. Cationic superoxide dismutase or cationic nonenzyme proteins did not suppress inflammation. The observed suppression of two different types of inflammation (an immune and a nonimmune arthritis) by catalase and peroxidase suggests that elimination of peroxides contributes to the suppression of an inflammatory response. We would hypothesize that cationic enzymes offer the possibility for investigating the mechanisms of inflammation and, in addition, might be interesting from a therapeutical point of view. PMID- 4019780 TI - In vivo externalization of phosphatidylserine and phosphatidylethanolamine in the membrane bilayer and hypercoagulability by the lipid peroxidation of erythrocytes in rats. AB - Phospholipid distribution across erythrocyte membrane bilayer is asymmetrical. In normal erythrocytes, entire phosphatidylserine (PS) and most of the phosphatidylethanolamine (PE) is present on the cytoplasmic side of membrane bilayer, whereas phosphatidylcholine (PC) and sphingomyelin (SM) are predominantly present at the outer side of membrane bilayer. The present study was undertaken to determine whether membrane lipid peroxidation has any effect on the distribution of PS, PE, and PC across erythrocyte membrane bilayer in vivo in an animal model. Erythrocyte membrane lipid peroxidation was induced in rats by administering phenylhydrazine, an oxidant drug. Membrane phospholipid organization was determined by using bee venom phospholipase-A2 and indirectly by measuring clotting time on recalcification of normal human platelet-poor plasma in the presence of Russell's viper venom. Phenylhydrazine administration to rats caused significant membrane lipid peroxidation as measured by the accumulation of malonyldialdehyde (MDA), an end product of fatty acid peroxidation, as well as externalization of a significant portion of PS and PE from the inner to the outer side of membrane bilayer in erythrocytes. There was a significant positive correlation (r) between the amount of MDA accumulated in the erythrocytes and the movement of PS (r = 0.92) and PE (r = 0.96) from inner to the outer membrane bilayer and PC (r = 0.81) from outer to the inner membrane bilayer. Erythrocytes of phenylhydrazine-treated rats also showed significantly reduced clotting time. This reduction in clotting time had a significant positive correlation with MDA accumulation (r = 0.92) and PS externalization (r = 0.90). Both the effect of phenylhydrazine on erythrocyte membrane lipid peroxidation and alterations in phospholipid organization and coagulability were blocked when rats were simultaneously administered with vitamin E or C antioxidants. PMID- 4019781 TI - Role of the kidneys in the metabolism of plasma mevalonate. Studies in humans and in rhesus monkeys. AB - Studies were carried out in humans and in rhesus monkeys to determine the role of the kidneys in the metabolism of circulating mevalonic acid (MVA). Following intravenous infusion of [14C]MVA and [3H]cholesterol, there was a rapid appearance of [14C]squalene in the kidneys that exhibited a significantly longer half-life than plasma or hepatic squalene. In man and in rhesus monkeys there was a rapid equilibration between newly synthesized cholesterol from MVA and exogenously administered cholesterol in all tissues except the kidneys, where the specific activity ratio of newly synthesized to exogenous cholesterol was significantly higher. Estimates of the quantitative metabolism of intravenously infused radiolabeled MVA in the monkey demonstrated that 23% was excreted in the urine, 67% metabolized to cholesterol (58% in nonrenal tissues and 9% in the kidneys), and 10% catabolized to CO2 and nonsteroid products. Measurements of MVA metabolism in anephric and uninephric patients demonstrate that, in the absence of renal uptake of MVA, exogenous and newly synthesized cholesterol achieve almost instantaneous equilibrium in the plasma; whereas in control subjects with normal renal function, this equilibration required at least 21 d for the two cholesterol decay curves to become parallel. These results suggest that the kidneys are solely responsible for the observed disequilibrium between newly synthesized and exogenous cholesterol; we suggest that this was due to the delayed release of newly synthesized cholesterol from the kidneys into the plasma compartment following intravenous infusion with radiolabeled MVA. The data document the importance of the kidneys in the metabolism of circulating MVA. However, calculation of the quantitative significance of this pathway in relation to whole body MVA metabolism indicates that renal metabolism of MVA accounts for approximately 0.1% of daily MVA turnover, and that alterations in this pathway due to any form of renal pathology would not result in significant changes in hepatic or whole body sterol synthesis rates. We urge caution in the use of radiolabeled MVA in long-term kinetic studies of sterol metabolism because our data show that the plasma compartment of MVA is not necessarily in isotopic equilibrium with tissue MVA. PMID- 4019783 TI - Increased amounts of a novel penicillin-binding protein in a strain of methicillin-resistant Staphylococcus aureus exposed to nafcillin. AB - In addition to the four typical penicillin-binding proteins (PBPs), a strain of heterogeneously methicillin-resistant Staphylococcus aureus produced an extra 78 kD PBP (PBP 2a) that had a low affinity for nafcillin and penicillin. Addition of nafcillin to cultures of this strain caused a rapid increase in the amount of this PBP in cell membranes. This increase occurred at subinhibitory concentrations of drug within minutes of exposure, and was blocked by inhibitors of protein and RNA synthesis. This suggests that the synthesis of PBP 2a can be stimulated by exposure to beta-lactam antibiotics. This process may, in part, explain the heterogeneity in methicillin-resistant S. aureus. PMID- 4019782 TI - Isolation and characterization of a colonic autoantigen specifically recognized by colon tissue-bound immunoglobulin G from idiopathic ulcerative colitis. AB - Patients with idiopathic ulcerative colitis (UC) have a colonbound antibody (CCA IgG) that reacts with colon tissue extracts. We have partially characterized a colonic protein that is specifically recognized by CCA-IgG. CCA-IgG was eluted from operative colon specimens from 10 patients with UC. A colon tissue-bound IgG was similarly eluted from six patients with Crohn's colitis, two with ischemic colitis, and one with diverticulitis. Purified serum IgG from patients with Crohn's disease, from normal subjects and a patient with myeloma were also used as additional controls. For detection of antigen(s), tissue extracts were prepared from 26 specimens of colon (UC, 12; Crohn's disease, 6; normal, 4; other controls, 4), 8 specimens of human normal stomach, duodenum, ileum, and liver (2 each). Tissue extracts were also prepared from rats and mice, including germ-free rat colons and rat's fetal colons. Immunorecognition of CCA-IgG to the tissue extracts was examined by affinity-column chromatography and by transblot analysis. Tissue-extracted proteins were electrophoresed in SDS-polyacrylamide gel, transferred to nitrocellulose sheet, and probed with iodinated CCA-IgG, colonic IgG from other inflammatory bowel disease patients, UC serum IgG, and control serum IgG. Although many proteins were present in colon tissue extracts, 9 of 10 CCA-IgG consistently recognized a protein of 40 kD. None of the nine IgG preparations from colon specimens of patients with Crohn's colitis and other colonic inflammatory diseases reacted with the 40-kD protein. Five of six symptomatic UC serum IgG and none of eight control serum IgG reacted with the 40 kD protein. The 40-kD protein was present in all colon specimens and it appeared to be organ specific. It was absent in mouse and rat tissues, including colon. The 40-kD protein is not actin and nor a part of the Ig molecule. These results suggest that the 40-kD protein is a colonic "autoantigen" that may initiate a specific IgG antibody response in UC. PMID- 4019784 TI - Identification of the lymphokine soluble immune response suppressor in urine of nephrotic children. AB - Patients with minimal change nephrotic syndrome (MCNS) frequently have suppressed in vivo and in vitro immune responsiveness of uncertain etiology. Because increased suppressor cell activity has been associated with this disease, urines from MCNS patients were screened for activity of the lymphokine soluble immune response suppressor (SIRS), a product of concanavalin A- or interferon-activated suppressor T cells. Urines from untreated MCNS patients suppressed polyclonal plaque-forming cell responses of cultured splenocytes. This suppressive activity was identified as human SIRS by the following functional and physical criteria: molecular weight estimated by gel filtration; kinetics of suppression; inhibition of suppression by catalase, levamisole, and 2-mercaptoethanol; abrogation of activity by acid or protease treatment; elution pattern on high performance liquid chromatography; and cross-reactivity with monoclonal antimurine SIRS antibodies. Suppressive activity disappeared from urine after initiation of treatment but before remission of symptoms. Urines were tested from 11 patients with MCNS, all of whom excreted SIRS. In addition, two nephrotic patients with acute glomerulonephritis and three nephrotic patients with membranoproliferative disease excreted SIRS, but other nephrotics and all nonnephrotic patients did not. These results indicate that excretion of SIRS occurs in certain cases of nephrotic syndrome and that the presence of SIRS in the urine is not accounted for solely by the presence of proteinuria or nephrosis. Serum from four nephrotic patients also contained SIRS, whereas neither serum nor urine from six normal subjects contained SIRS activity. The systemic presence of SIRS in these four patients, and the identification of SIRS in urines from a larger group of patients, suggest a possible role for SIRS in the suppressed immune responses often found in nephrotic syndrome. PMID- 4019785 TI - Carboxyterminal peptide fragments of the beta subunit are urinary products of the metabolism of desialylated human choriogonadotropin. AB - Previous investigations of patients with gestational trophoblastic neoplasia have shown that their urines often contain carboxyterminal peptide (CTP) fragments of the choriogonadotropin (hCG) beta-subunit as well as forms of hCG deficient in sialic acid. In order to determine whether beta-CTP fragments are among the urinary products of the peripheral degradation of desialylated hCG (as-hCG), using a continuous infusion technique, we gave highly purified as-hCG to humans. Six healthy subjects were given a loading dose of 0.8 mg of as-hCG followed by an infusion of the same preparation. An overall mean infusion rate of 62.9 micrograms/min was maintained for 6 h, and the mean serum concentration of as-hCG achieved during the infusion was 72.1 ng/ml. In all six subjects, beta-CTP fragments were the predominant immunoreactive forms of as-hCG in urine obtained during the infusion. In contrast, the urine of subjects infused with hCG has been shown to contain hCG itself, but nil beta-CTP fragments or as-hCG. After the as hCG infusion was stopped, the excretion of the beta-CTP fragments in urine declined rapidly. There were no beta-CTP fragments detectable in sera obtained during the infusion or in sera incubated with as-hCG at 37 degrees C. After incubation with as-hCG for 4 h, the urine of normal subjects contained small amounts of beta-CTP fragments; however, the apparent proteolytic activity was too low to account for either the quantity of beta-CTP fragments produced during the infusion or the extremely low levels of as-hCG in the urine. These data demonstrate the existence in humans of a peripheral metabolic pathway that cleaves beta-CTP fragments from as-hCG and allows their excretion in urine. Thus, the frequent presence of beta-CTP fragments in the urines of patients with gestational trophoblastic neoplasia can be accounted for in part by the metabolism of the forms of hCG that bear an altered carbohydrate structure, which are prevalent in this disease. PMID- 4019786 TI - Posttranslational cleavage of proinsulin is blocked by a point mutation in familial hyperproinsulinemia. AB - Familial hyperproinsulinemia is characterized by the accumulation of proinsulin like material (PLM) in the plasma of affected patients. This disorder is inherited in an autosomal dominant fashion. The accumulation of PLM is thought to be due to the impaired conversion of proinsulin to insulin. Although PLM has been suggested to have an amino acid substitution, it has been impossible to locate and identify a substituted amino acid, due to the difficulty in isolating sufficient amounts of PLM from plasma samples. Therefore, we analyzed leukocyte DNA from one member of a proinsulinemic family, and we found a point mutation that changed guanine to adenine in the insulin gene. This transition implies that a substitution of histidine for arginine has occurred at amino acid position 65. Furthermore, it indicates that arginine at 65 is essential for the conversion of proinsulin to insulin. Our results suggest a novel mechanism by which disease can be incurred: a heritable disorder can result from a posttranslational processing abnormality caused by a point mutation. PMID- 4019787 TI - Hamster female protein, a sex-limited pentraxin, is a constituent of Syrian hamster amyloid. AB - Female protein (FP) is a pentraxin of Syrian hamster which is a homologue of two human pentraxins, C-reaction protein (CRP) and amyloid P component (AP). Functionally, FP has been shown to be similar to CRP, although FP has more homology at the amino terminus with AP. The present work investigated amyloid in the Syrian hamster to determine whether FP was involved in a manner analogous to AP. FP was found to be a constituent of Syrian hamster amyloid. This conclusion was based on the following results: (a) FP was consistently detected in amyloid deposits by fluorescent microscopy with specific antisera; (b) The amount of FP extractable from hamster livers directly correlated with the presence of amyloid; and (c) 125I-FP injected intravenously into amyloidotic hamsters rapidly left the intravascular compartment and was found subsequently in amyloid deposits. This unusual alteration of plasma metabolism and amyloid localization of 125I-FP was a characteristic finding in amyloidotic hamsters and was specific for 125I-FP. Therefore, as an amyloid component, FP appears to be functionally similar to human AP. However, FP synthesis is under sex steroid control and the unique sex limited expression of this pentraxin was associated with an equally novel propensity for deposition of amyloid in female hamsters under normal or experimental conditions. Thus, a high serum level of FP, as found in normal females or diethylstilbestrol-treated males, was associated with enhanced amyloidosis. Although speculative at present, a primary role for serum FP in hamster amyloid deposition may be experimentally approachable by hormonal manipulation of FP synthesis. PMID- 4019788 TI - Quantification of reduced haloperidol and haloperidol by radioimmunoassay. AB - A radioimmunoassay for reduced haloperidol and haloperidol has been developed by using a simple derivatization-separation step prior to assay with an antibody cospecific for both compounds. The detection limit of the assay is less than 25 pg and shows no cross reactivity to other metabolites. The intraassay coefficient of variation for reduced haloperidol and haloperidol were 9.0 and 8.2% respectively and the interassay coefficients of variation were 9.0 and 10.6% respectively at 5-10 ng/ml. As many as 30 patient samples can be analyzed for both compounds in a single day. PMID- 4019789 TI - The Committee on Review of Medicines. PMID- 4019790 TI - Evaluation of a pharmacist-managed anticoagulation clinic. AB - Medical records were retrospectively analyzed to evaluate the success of a pharmacist-managed Anticoagulation Surveillance Clinic (ASC). The 78 patients in group I were followed by the ASC. The 17 patients in Group II were followed by other Veterans Administration Medical Center clinics. Demographic characteristics, warfarin indication and potentially complicating conditions were comparable between the groups. Group I patients had shorter intervals between visits to the clinic than Group II patients. Although not statistically different compared to Group II, Group I patients had better prothrombin time control. Group I patients also had fewer complications per treatment year (6.9% vs 9.0%) and received fewer potentially interacting drugs. The ASC was at least as successful as the other clinics in managing patients on warfarin, and results compared very favorably to those reported in the literature for other anticoagulation clinics. PMID- 4019791 TI - Differential pulse polarographic determination of formaldehyde in stored noxythiolin solutions. AB - A differential pulse polarographic method has been developed for the determination of formaldehyde, by means of its kinetic current, in noxythiolin solutions. The assay conditions have been optimized so that the noxythiolin decomposition reaction was not affected. The method had the advantage of rapidity with an analysis time of about 10 min per sample. Thus formaldehyde was determined in noxythiolin solutions prepared and stored under typical clinical conditions. The low concentrations of formaldehyde present in all solutions were insufficient to account for the known cidal action of noxythiolin. There must therefore be some doubt that the mode of action of noxythiolin is simply due to formaldehyde produced as a result of the decomposition of noxythiolin in aqueous solution. PMID- 4019792 TI - Impurity of thrombin preparations for clinical use. AB - Recent advances in the treatment of upper gastro-intestinal bleeding has led to the use of thrombin preparations in this condition. In the present investigation, the purity of thrombin preparations from one American pharmaceutical company and two Japanese pharmaceutical companies was examined using immunological and biological methods. An SDS-PAGE study revealed that each preparation contained various proteins other than thrombin. An immunological study revealed that each of the thrombin preparations contained proteins which were of at least two types. The thrombin preparations exhibited various biological activities other than thrombin activity, and their activities were widely different. Preparation A showed the strongest activity among the three, in terms of amidolytic activity, gamma-gamma dimer production rate, fibrin production rate, release of fibrinopeptide A, and anti-stretch activity. However, preparation A revealed the strongest binding activity to antithrombin III. Preparation B had the least contamination while preparation C showed the highest activity in terms of fibrinolytic and platelet-aggregating activity. Thus, each thrombin preparation had a greater or lesser degree of impurity, and it would appear that purer preparations are required for local administration in the treatment of upper gastro-intestinal bleeding. PMID- 4019793 TI - A note on the contamination of eye-drops following use by hospital out-patients. AB - Examination of 273 eye-drops, returned to a hospital pharmacy by out-patients showed that 27% were contaminated. Common contaminants included Bacillus spp, Staphylococcus albus and Sarcina spp. Those eye-drops containing the preservatives chlorbutol or thiomersal showed above average levels of contamination, thus questioning the suitability of these preservatives for ophthalmic preparations. PMID- 4019794 TI - Theophylline versus aminophylline in rectal administration. AB - This study was undertaken to compare the bioavailability and the in vitro release rates of theophylline from suppositories containing either theophylline or aminophylline. The absorption of theophylline from solution and from freshly prepared suppositories formulated with Suppocire and containing anhydrous theophylline 250 mg or aminophylline 300 mg was investigated in six healthy volunteers in a blind crossover design experiment. Venous blood samples were collected before drug administration and at 1, 2, 4, 6 and 8 h afterwards. Theophylline serum levels were measured spectrophotometrically. The pharmacokinetic parameters obtained: Cmax 6.7 and 5.4 micrograms ml-1, tmax 2 h, and F8h 0.79 and 0.83 for theophylline and aminophylline, respectively, show that the two formulations are almost bioequivalent, with a slightly higher Cmax for theophylline. The in vitro release rate of theophylline from freshly prepared formulations was, however, higher (4.8 mg min-1) from aminophylline suppositories relative to those containing theophylline (2.9 mg min-1). This lack of correlation between the in vitro and in vivo results is explained by the different drug thermodynamic activities in the processes of release and membrane penetration. Thus, a better water-solubility does not automatically point to a better rectal bioavailability. The release rate of aminophylline suppositories tested after 1-year storage at room temperature dropped from 4.8 to 0.5 mg min-1. The bioequivalence of theophylline and aminophylline freshly prepared suppositories and the stability problems associated with fatty-base aminophylline suppositories indicate that the choice of ethylenediamine derivative of theophylline is an empirical development, theoretically unjustified, and must be replaced by theophylline reformulations. PMID- 4019795 TI - Dosage of tobramycin in cystic fibrosis--a short report. AB - A 15 kg, 7-year-old girl with cystic fibrosis was admitted with a chest infection. It was found that a tobramycin, 12 mg/kg/day (standard recommended dose 6-7.5 mg/kg/day), was required to obtain acceptable plasma levels and that the volume of distribution varied in line with the patient's weight changes. PMID- 4019796 TI - Chlamydial endometritis. AB - Endometrial biopsies were obtained from 32 women with suspected pelvic inflammatory disease, of whom 23 (72%) had histopathological evidence of endometritis. Chlamydia trachomatis was isolated from the endometria of nine (39%) women (chlamydia group) but not from the other 14 (non-chlamydia group). Severe plasma cell endometritis and lymphoid follicles with transformed lymphocytes were significantly more common in the chlamydia group than in the non chlamydia group. This suggests that C trachomatis is an invasive endometrial pathogen which often causes severe inflammation. The association was independent of predisposing factors such as use of intrauterine contraceptive devices. PMID- 4019797 TI - Changes in circulating immune complex concentrations and antibody titres during treatment of Q fever endocarditis. AB - Serum samples from 20 patients with Q fever endocarditis were tested for the presence of circulating immune complexes to see whether their concentrations correlated with antibody titres during treatment and whether they could be used to monitor the response to antimicrobial treatment. Circulating immune complexes were found in all 20 patients. The concentrations in 15 patients correlated with either or both of the Q fever phase 1 and phase 2 antibody titres obtained during treatment. In the other five patients no correlation with the antibody titres was found. There was no association between circulating immune complex concentrations and clinical response to treatment. PMID- 4019798 TI - Histopathological classification and malignant change in gastric polyps. AB - A total of 611 gastric polyps from 275 cases were studied and were classified into four subtypes. Type I was the most common type and types II, III, and IV were less common. Type I and II, considered to be non-neoplastic polyps because of the absence of dysplasia, showed an extremely low malignant potential. Type III showed a two layer structure, the upper layer of which was composed of dysplastic epithelia. This type showed a low malignant potential despite the dysplasia. The type IV polyp showed macroscopical and histological findings similar to those of colonic adenoma. This type was considered to be truly neoplastic and to be the most important of the four subtypes because of its high malignant potential. Type III and IV should be clearly separated and treated differently. PMID- 4019799 TI - Density of mucosal mast cells in the lamina propria of the colon and terminal ileum of children. AB - Ileal and colonic biopsies from children observed to be histologically normal were fixed in Carnoy's fluid, sectioned, and stained by the chloroacetate esterase reaction. The density of mucosal mast cells was higher in the terminal ileum than the colon, but did not vary significantly within the colon. PMID- 4019800 TI - A quantitative study of immunoglobulin containing cells in the differential diagnosis of acute colitis. AB - In colonic biopsies of 33 patients with acute colitis caused by campylobacter, salmonella, or shigella immunoglobulin containing cells were determined quantitatively using an indirect immunoperoxidase technique and morphometry with a graphic tablet. The findings were compared with those of 10 patients without histological abnormalities, 10 patients with Crohn's disease of the colon, and 10 patients with ulcerative colitis. Biopsies of patients with acute infectious colitis had increased numbers of IgA containing cells and to a lesser extent IgM containing cells but not IgG containing cells compared with controls. Compared with the patients with active chronic idiopathic inflammatory bowel disease the patients with acute colitis showed significantly lower relative and absolute numbers of IgG containing cells. We therefore conclude that quantitative assessment of immunoglobulin containing cells in colonic biopsies may be useful in the differential diagnosis of acute infectious colitis and chronic idiopathic inflammatory bowel disease. PMID- 4019801 TI - Histological features of sclerosing cholangitis in patients with chronic ulcerative colitis. AB - Primary sclerosing cholangitis was diagnosed radiologically in 16 of 681 patients (2.2%) with chronic ulcerative colitis in a follow up study at the gastroenterology unit in Oxford. On the basis of established histological criteria, the liver biopsy was considered diagnostic in only half of the cases. The histological findings in these cases were therefore reassessed to determine whether the accuracy of biopsy diagnosis could be improved. The most common specific histological feature was periductal concentric fibrosis of small interlobular bile ducts, even in the absence of inflammation. Other common features were bile ductular proliferation associated with diminution or absence of interlobular bile ducts. Degeneration of bile duct epithelium and diffuse infiltration of portal tracts by mononuclear cells and polymorphonuclear leucocytes were accompanying features. Piecemeal necrosis without rosette formation was found in about half the biopsies. When all these features were considered together a biopsy diagnosis of primary sclerosing cholangitis was established in 14 of 16 cases. PMID- 4019802 TI - Thalassaemia trait and pregnancy. AB - The haematological variables, haematinic state, and placental function of more than 2000 pregnant women, heterozygous for either alpha- or beta-thalassaemia genes, were examined during pregnancy. Four features emerged. Firstly, it was possible by discriminant function analysis of haematological variables to distinguish in pregnant patients between the anaemia caused by thalassaemia trait and that caused by iron deficiency. Secondly, patients with thalassaemia become significantly more anaemic in pregnancy, beta more than alpha, but this was mainly due to plasma dilution. From the data percentile curves were drawn for each type of thalassaemia which predicted the patients' expected "normal" haemoglobin throughout gestation. Thirdly, patients with alpha-thalassaemia had the same incidence of iron deficiency as normal pregnant patients, whereas in those with beta-thalassaemia it was four times less common. The incidence of folic acid and vitamin B12 deficiency was the same in all groups. Finally, as assessed by serum oestriol concentration, there did not appear to be any abnormality of placental function or fetal development associated with maternal thalassaemia, and, also, there seemed to be no increase in maternal or fetal morbidity in pregnancy. PMID- 4019803 TI - Pleural fluid ferritin concentrations in human disease. AB - The concentration of ferritin was measured in the pleural fluid of 108 patients with pleural effusions. In all groups of patients the ferritin concentration was higher in pleural fluid than in serum. The greatest differences, with up to 100 times more ferritin in the pleural fluid, were found for patients with rheumatoid pleurisy, malignant effusions, and empyema. In patients with non-malignant inflammatory pleural effusions the concentration of ferritin in pleural fluid correlated significantly with other pleural fluid indices of inflammation: there was a positive correlation with lactate dehydrogenase activity and a negative correlation with concentrations of glucose and complement components C3 and C4. Ferritin was detected immunocytochemically only in the macrophages found among the pleural fluid cells. Our study shows that large amounts of ferritin accumulate locally in the pleural cavity in certain types of pleural inflammation. The accumulation is probably partly the result of increased local reticuloendothelial system activity. Determination of the concentration of ferritin in pleural fluid may provide corroborative information for differential diagnosis and may further our understanding of the pathogenetic events that lead to the perpetuation of inflammatory activity in pleural effusions. PMID- 4019804 TI - Simplified procedure for tissue culture in routine detection of cytotoxins. PMID- 4019805 TI - Isolation of Bacillus circulans from a wound infection. PMID- 4019806 TI - Detection of antibodies to Staphylococcus epidermidis in infected total hip replacements by an enzyme linked immunosorbent assay. PMID- 4019807 TI - Expression of leucocyte common antigen and epithelial membrane antigen in plasmacytic malignancies. PMID- 4019808 TI - User unfriendly drugs--fillers, additives, excipients. PMID- 4019809 TI - Serial monitoring and achievement of steady state nortriptyline plasma levels in depressed children and adolescents: preliminary data. AB - Children and adolescents 6 to 16 years old (N = 25), who were diagnosed as having major depressive disorder, received a fixed daily dose of nortriptyline during an 8-week period. Nortriptyline plasma levels were drawn and assayed weekly. Data were analyzed for the total sample (N = 25) and separately for the subgroup of 6 to 9 year olds (N = 9) and for the subsample of 10 to 16 year olds (N = 16). There were no significant differences between the day 7 (week 1) plasma levels and the means of weeks 2 to 8 or between the means of weeks 1 to 4 and 5 to 8 within the total sample or within either subgroup. These findings suggest that nortriptyline steady state plasma levels within the pediatric age range are achieved by day 7 (week 1) and that nortriptyline (during the pediatric years) does not induce its own metabolism during an 8-week period. The achievement of steady state by day 7 is similar to that found in adults. The mean coefficients of variation were calculated for the total sample and for each subsample and were 13.7 +/- 4.0% (range, 8 to 20%) for the 6 to 9 year olds; 13.8 +/- 3.2% (range, 10 to 21%) for the 10 to 16 year olds; and 13.8 +/- 3.4% (range, 8 to 21%) for the total sample. These coefficients of variation are similar to the 10 to 20% range reported in adult subjects.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4019810 TI - Desipramine plasma levels and response in elderly melancholic patients. AB - The relationship of response and plasma desipramine concentrations was examined in elderly depressed patients to determine whether they were more sensitive to the antidepressant effects of the drug and whether they would respond at lower plasma concentrations than younger patients. Twenty-five inpatients over the age of 60, who met criteria for major depression with melancholia, were unipolar, were not delusional, were without active medical illness or definite brain disease, and were still depressed after 1 week of hospitalization off psychotropic drugs, were treated with desipramine (2.5 mg/kg) for 3 weeks. Of the 18 patients completing the drug trial, six responded and 12 did not. Desipramine levels of responders (median, 126 ng/ml) were higher than those of nonresponders (median, 81 ng/ml; Mann-Whitney test, p less than 0.05). The threshold for response was the same as the threshold (115 ng/ml) observed in 31 nondelusional melancholic patients under the age of 60 treated in a similar manner with desipramine. Among elderly patients with levels above 115 ng/ml, four of five responded, and below this level, two of 13 responded (Fisher's exact test, p less than 0.025). Five patients not responding to the initial 3-week trial responded when desipramine was increased and the plasma level rose above 115 ng/ml. The data indicate that elderly melancholic patients to not respond to lower desipramine plasma concentrations and that therapeutic levels are similar to those for younger melancholic patients. The doses of desipramine needed to reach these levels were also similar to those required in younger patients. PMID- 4019811 TI - Akinesia and mutism following a methylphenidate challenge test. AB - A case of akinesia and mutism is described in a menopausal, depressed woman with onset following a mood challenge with 40 mg of methylphenidate taken orally over a 3-hour period. Various diagnoses are considered with preference given on clinical grounds to conversion disorder precipitated by drug-induced dysphoria. It is suggested that increased susceptibility to dysphoria may have been related to prior clomipramine administration and hypoestrogenism. PMID- 4019812 TI - Successful treatment of psychotic depression with carbamazepine. AB - A patient with recurrent episodes of major depression with psychotic features was treated successfully with carbamazepine after unsatisfactory response to other interventions. Since psychotic depression is often difficult to treat with medications, carbamazepine may be a useful addition to the clinician's pharmacological armamentarium. PMID- 4019813 TI - Cimetidine-doxepin interaction. PMID- 4019814 TI - Managing a case of bipolar disorder, diabetes, and hypotension. PMID- 4019816 TI - Elementary school age children's comprehension of specific idiomatic expressions. AB - This study explored the ability of elementary school age children to comprehend six idiomatic expressions. Eighty linguistically normal children, 20 from each of four different grade levels (kindergarten, second grade, fourth grade, and sixth grade) participated as subjects. All of the children completed a task designed to probe comprehension of specific idioms. A short story was presented, after which the subjects were required to identify events in the story, which were described using idiomatic phrases. When examined as a group, comprehension of the idioms studied improved with increasing age. However, when examined individually, performance was found to be highly variable from idiom to idiom. These results are discussed with regard to clinical implications in the assessment and management of language-disordered children. PMID- 4019815 TI - Deaf children's revision behaviors in conversations. AB - This study was designed to investigate school-age deaf children's responses to a listener's indication of communication breakdown and to determine if the deaf children's responses were related to their syntactic or semantic abilities and/or typical mode of communication. Subjects were 14 deaf children between the ages of 5 yr, 10 mo and 8 yr, 11 mo. Approximately once every 3 min during a 60-min conversation, the experimenter said, and simultaneously signed, "What?" The child's responses to the "What?" probe were classified as Revision, Repetition, and No Response. Revisions were categorized into eight subcategories involving changes in sentence constituents and supraconstituents. Revisions were the most frequent responses when communication broke down. Most of the children's revisions involved changes in sentence constituents. The frequency of revisions, repetitions, and no responses was related to the children's level of syntactic production. PMID- 4019817 TI - Remediation of intonation contours of hearing-impaired students. AB - Incorrect production of intonation contours is a common phonatory problem among the hearing impaired. Programs designed to remediate this problem include those that employ a systematic sequence of training steps as well as those that use sensory aids to provide visual or tactile feedback of contour production. A speech-training program that incorporates both is described. The program utilizes a hierarchical curriculum with either a tactile or a visual display of fundamental frequency for the remediation of incorrectly produced intonation contours. The displays are interfaced with a microprocessor, thus allowing regular collection of data and monitoring of the program's effectiveness. Three case studies are presented as representative examples of the students' progress. Implementation of the systematic curriculum with the use of the sensory aids results in improved performance in the phonatory skills of these students. The successes and difficulties encountered in speech training are discussed. PMID- 4019818 TI - Mandibular position during children's defective /s/ productions. AB - Mandibular displacement during /s/ production was monitored via a mercury strain gauge which was taped to the face of two normally articulating and six /s/ misarticulating children. Simultaneous audio and jaw displacement visicorder traces were produced from an FM-tape recording of each experimental session, and were subsequently analyzed. Results indicated that various /s/-misarticulating subgroups exhibit different mandibular positions during /s/-production, and phonetic contextual effects upon mandibular position also vary by articulatory type. PMID- 4019819 TI - A descriptive analysis of high school seniors with speech disabilities. AB - Of over 26,000 high-school seniors for whom survey data from the recent High School and Beyond study were complete, 278 identified themselves as having speech disabilities. The data on these latter students were compared to those on their nonimpaired peers with regard to demographic variables and measures of achievement, personal characteristics, and relationship to school and work. These orally handicapped pupils tended to be older, more often from linguistic minority groups, and tended to present more additional handicapping conditions. The data also showed the impaired group at a disadvantage regarding achievement, self image, motivation, and career aspirations. Some possibilities for ameliorating these conditions are suggested. PMID- 4019820 TI - Self-efficacy scaling by adult stutterers. AB - A scale was developed for estimating adult stutterers' confidence for entering and maintaining fluency in a variety of speaking situations. This Self-Efficacy Scale for Adult Stutterers (SESAS) was administered to 20 adult stutterers along with the shortened form of the Erickson Scale of Communication Attitudes and the Perceptions of Stuttering Inventory. Twenty nonstuttering adults were also given the SESAS the self-efficacy scores significantly differentiated between stutterers and nonstutterers. SESAS scores were correlated with the Erickson Scale (-0.71) and the Perceptions of Stuttering Inventory (-0.52). A correlation of -0.51 was found for SESAS scores and stutterers' self-ratings of severity. Test-retest reliability for the SESAS averaged 0.89. The results suggest that with continued development, self-efficacy scaling may be a useful technique for measuring one aspect of change during treatment. PMID- 4019821 TI - New directions in community health. PMID- 4019822 TI - Do community mental health centers serve the chronically ill? The New York experience. AB - Some critics of the community mental health movement have contended that fewer clients with serious mental disorders are seen by local mental health centers. This statewide study compared patients being treated at community health centers (CMHC) with those seen at state psychiatric hospitals in New York State. Minor differences in psychiatric diagnoses and requisite levels of care needed emerged between short-term state psychiatric patients and CMHC inpatients. Suggestions for future research are offered. PMID- 4019823 TI - Evaluation and application of continuity measures in primary care settings. AB - Continuity of contact between patients and physicians has become an important criterion of quality primary care. Using three measures of continuity that have appeared in the literature, this article examines, through the use of simulated data and through application to data from five primary care settings, the differences and utility of these approaches for measuring continuity. Further, these measures are applied to four selected diagnoses from each of the five sites, and the observed continuity scores afforded patients with these diagnoses are compared with those expected based on the population. Finally, the scores are correlated with the number of return visits prescribed and kept and with the rate at which laboratory studies are ordered. The findings indicate that site-specific differences in continuity prevail even after adjustments in the number of visits. Continuity based on selected diagnoses is greater, for the most part, than continuity afforded the patient population. Finally, continuity is related to the number of return visits prescribed but not to the number kept or the rate at which laboratory studies are ordered. The implications of continuity for other aspects of quality patient care are discussed. PMID- 4019824 TI - The multidimensionality of patient satisfaction with a clinic visit. AB - Three hypotheses regarding the factor structure of patient satisfaction with an ambulatory health care encounter were tested in a New York medical center outpatient sample. All three hypotheses were generally supported. It was found that patients evaluated four distinct aspects of the clinic visit: doctor conduct, convenience, appointment getting, and the visit in general. A significant proportion of the variance in general satisfaction was explained by satisfaction with doctor conduct and satisfaction with convenience. Three factor scales of patient satisfaction were developed with demonstrable internal consistency reliability. Some possible effects of response method on satisfaction ratings were studied; these method effects were not substantial, and it is suggested that this type of psychometric procedure be used in further studies of patient satisfaction. PMID- 4019825 TI - A spin echo chemical shift MR imaging technique. AB - A new method is described that produces images of either the fat or water component in tissues in magnetic resonance imaging. Only a single scan is required, with scan times of a few minutes. Chemical shift selectivity is achieved in the spin echo process by controlling the spectral content of the 180 degree pulse that induces the spin echoes. A theoretical analysis of the selective spin echo process for the case of a radio frequency pulse of constant amplitude shows that spin echoes will be suppressed for certain values of offset frequency that are similar to, but different from, the frequencies at which the Fourier spectrum of the pulse vanishes. The theory was confirmed by experiment on a water phantom. The imaging technique was tested on both a phantom of oil and water and on a human forearm. Excellent suppression of the water signal was found in the fat images, and the small fat component seen in the water images is attributable to components of the triglyceride molecule for which spectral lines overlap those of water. The forearm images also showed blood flow effects in the water image that were not visible in the fat image. The relationship of this method to other proposed methods of chemical shift imaging is discussed. PMID- 4019826 TI - MR imaging of meningiomas including studies with and without gadolinium-DTPA. AB - The magnetic resonance (MR) appearances in 12 successive cases of histologically verified meningioma are described. In six of these cases intravenous gadolinium diethylenetriamine pentaacetic acid (Gd-DTPA) (0.1 mmol/kg) was administered. Each of the eight tumours for which T1 was measured displayed an increase in T1 above that of white matter although the T2 was in the normal range for brain in two of four cases. Inversion recovery was the most useful sequence for demonstration of the tumour prior to administration of intravenous Gd-DTPA and also displayed the highest level of contrast enhancement after Gd-DTPA. The overall findings compared well with contrast enhanced X-ray CT. PMID- 4019827 TI - Intracranial hematomas studied by MR imaging at 0.17 and 0.02 T. AB - The contrast in magnetic resonance (MR) images relies mainly on the relaxation time differences between the tissues. The relative differences in relaxation times T1 are bigger at lower field strengths, although the absolute values of T1 are smaller. A shorter T1 is also advantageous for the contrast of the T2 and proton density weighted images because of the more complete recovery of the spin system during the repetition time TR. Scrutiny of the clinical results of MR shows some unsolved problems in the specificity of diagnosing fresh intracranial hematomas. Low field MR imaging at 0.02 T seems to offer new vistas in this sense. Fresh subdural hematoma was more easily detected and differentiated at 0.02 T than at 0.17 T. The T2 of fresh intracranial hematomas was rather short compared with cerebrospinal fluid and edema and, unlike T1, was not highly dependent on magnetic field strength. The different visualization of acute versus late intracerebral hematoma and the changes during the resorption were demonstrated in follow-up studies of two patients at 0.17 T and of one at 0.02 T. In one patient the same lesion was imaged successively at both field strengths, showing the divergent contrast in the inversion recovery images at 0.02 and 0.17 T. PMID- 4019828 TI - Wall of infundibular recess: a CT and MR study. AB - A ring of enhancement immediately posterior to the optic chiasm has been observed on postcontrast, thin section, axial CT. This ring represents enhancement of the infundibular recess' wall and does not have any pathologic significance. Magnetic resonance confirmed this anatomic interpretation. PMID- 4019829 TI - Toward quantitative characterization of the caudate nucleus through CT image enhancement. AB - Dilated lateral cerebral ventricles have been reported in association with psychiatric disorders. The dilatation is likely secondary to changes in anatomically related centers in the brain. Our attention is focused on the caudate nucleus and the need to develop quantitative characterization of it in psychiatric research. A computer method is described for accurately detecting the edges of the caudate nuclei in CT scans. The method consists of a two-dimensional filtering step to reduce image noise, followed by gradient computation for edge enhancement, and then an edge detection step to identify and record the caudate nuclei cross sections. Results from both head scans and synthetic images indicate that the method is successful even for low-contrast edges where the standard deviation of image noise approaches the difference in mean HU across the edge. The availability of an automated method of delineating the caudate nucleus permits the cross-sectional area and shape to be determined, the density to be estimated, and, from a set of closely spaced slices, volume information to be obtained. PMID- 4019830 TI - "Incomplete ring" sign: a simple method for CT detection of spondylolysis. AB - Multiple authors have pointed out the difficulty of detecting spondylolysis with lumbar CT. A simple method to detect spondylolysis on lumbar CT is described. Identifying one intact cortical ring for each vertebra absolutely excludes the diagnosis obviating the time-consuming need to search each image looking for positive evidence of the abnormality. If at least one intact cortical ring for each vertebra is not found, a defect in the ring at the appropriate position assures the diagnosis. PMID- 4019831 TI - MR image contrast and relaxation times of solid tumors in the chest, abdomen, and pelvis. AB - A retrospective study of 121 patients with tumors in the chest, abdomen, and pelvis was made to assess the degree of contrast between solid tumors and adjacent tissue on magnetic resonance (MR) spin echo (SE) images. Tumors examined were hepatomas (five patients), liver metastases (17), hemangiomas (seven), biliary carcinomas (eight), pancreatic carcinomas (five), renal tumors (15), adrenal tumors (eight), uterine tumors (17), bladder carcinomas (five), prostatic carcinomas (13), bone tumors (six), and lung carcinomas (15). A long repetition time (TR) and a long echo time (TE) were found the most useful to delineate tumors from liver, renal tumors from kidney, lung carcinoma from lung, pelvic tumors from muscle, and uterine tumors from the myometrium. A short TR and short TE provided the best contrast between tumors and fat and bone marrow. Therefore, for detection and staging of tumors, both a sequence with short TR and short TE and one with long TR and long TE are necessary. Pancreatic carcinomas were difficult to differentiate from liver and pancreas on all SE sequences used in the study. Contrast of adrenal tumors was independent of the sequence used. Some adrenal tumors were hypointense and some similar in intensity to the kidney. Further MR characterization of the tumors was limited. PMID- 4019832 TI - CT findings in pleural aspergillosis. AB - Two patients who underwent pulmonary resections for lung cancer developed delayed pleural abnormalities. In each instance CT confirmed the presence of pleural thickening, nodularity, and intrapleural masses proven to represent intrapleural aspergillomas. PMID- 4019833 TI - Primary intestinal lymphangiectasia: clinical and CT findings. AB - We present two patients with biopsy proven primary intestinal lymphangiectasia in whom CT demonstrated diffuse nodular thickening of small bowel without adenopathy or hepatosplenomegaly. One patient had extensive ascites. Although the CT findings are not specific to lymphangiectasia, they may allow one to suggest the diagnosis in the patient with protein losing enteropathy and help distinguish it from inflammatory bowel disease, lymphoma, celiac disease, or Whipple disease. PMID- 4019834 TI - Computed tomography of renal tuberculosis and its pathological correlates. AB - Computed tomographic studies of eight patients with proven renal tuberculosis demonstrated a spectrum of findings related to the extent and the severity of kidney involvement. In early or focal disease, obstruction of a single major calyx or a group of minor calyces was noted (four cases) with no excretion of contrast material into the affected calyces (three cases) and cortical thinning. Tuberculosis of the renal pelvis (five cases) was manifested by either pelvic dilatation secondary to ureteropelvic junction obstruction (three patients) or diffuse pelvic contraction (two patients). In far advanced disease (four cases) the kidneys were small and exhibited atrophy with replacement of parenchyma by one or more low density areas. Calcifications (37.5%) were identified in the parenchyma and within the calyces. Computed tomography may provide the first clue in suggesting the inflammatory nature of a renal mass and excluding a neoplastic process. Computed tomography is also of value in determining the full extent of extrarenal involvement and the amount of residual functioning parenchyma, both of which are critical in proper treatment planning. PMID- 4019835 TI - Computed tomography of acute renal failure secondary to rhabdomyolysis. AB - Two patients with rhabdomyolysis and renal failure were imaged with CT. The presence of a striate nephrogram, nephromegaly, and perinephric fluid has not previously been described on CT. Although nonspecific, these findings suggest the diagnosis of acute tubular blockade, and, once identified, administration of additional urographic contrast medium should be avoided. PMID- 4019836 TI - Computed tomography of prostatic and bladder rhabdomyosarcomas. AB - Rhabdomyosarcoma represents the most common soft tissue sarcoma in children. The CT findings in five patients with pelvic rhabdomyosarcoma are reported. In the three male patients the primary tumor originated in the prostate gland whereas in the two female patients the bladder was the primary site. The CT findings in the prostatic tumors included an enlarged, inhomogeneous prostatic mass with invasion of the perirectal fat. In two of these patients there was thickening of the levator ani muscle and one showed tumor invasion through the ischiorectal fossa and sciatic and obturator foramina into the pelvic musculature and bone. In the two patients with bladder tumors, one showed a large mass adjacent to the lateral aspect of the bladder and ascites, suggesting an ovarian primary tumor. The other patient with sarcoma botryoides (a subtype of rhabdomyosarcoma) had a diffusely thickened bladder. Two patients have had a follow-up CT demonstrating tumor regression posttherapy. The characteristically large size of these masses and propensity for local invasion in a young patient are typical features of pelvic rhabdomyosarcoma. PMID- 4019837 TI - Computed tomography of benign ovarian masses. AB - Although ultrasound is the primary imaging modality for evaluating benign gynecologic pelvic masses, CT may provide diagnostic information regarding ovarian masses that are discovered fortuitously. The relatively infrequent use of CT in evaluating the adnexa has resulted in a paucity of literature regarding the CT characteristics of benign ovarian masses. The CT appearances of 24 benign ovarian masses are presented. Pathologic diagnoses were ovarian cyst (nine), endometrioma (five), teratoma (three), serous cystadenoma (two), mucinous cystadenoma (two), thecoma (one), cystadenofibroma (one), and Brenner tumor (one). Benign ovarian cysts have characteristic homogeneous water density and smooth walls on CT. Single internal septations and slight wall irregularity are also common features, but soft-tissue mural or septal nodules are uncommon. Computed tomography can be diagnostic in evaluating cystic teratomas. Other benign ovarian masses exhibit a spectrum of CT appearances that is often nonspecific, and surgical or biopsy proof may be necessary to exclude malignancy. PMID- 4019838 TI - MR imaging in Fahr disease. AB - The calcifications of Fahr disease that are detected by CT in the dentate nuclei of the cerebellum, basal ganglia, and white matter of the cerebral hemispheres displayed three patterns with magnetic resonance imaging using the multiple echo technique: (a) cerebellar calcifications were undetected; (b) basal ganglia calcifications displayed low or no signal and appeared as "black" areas in four echoes; and (c) white matter calcifications displayed a high signal in the four echoes and appeared intensely white. The different behavior of the three calcified sites probably reflects different stages of the disease or different metabolic states with predominance of inert calcium deposits in the basal ganglia. In the white matter there is probably a higher concentration of binding proteins and mucopolysaccharides. PMID- 4019839 TI - MR imaging in adrenoleukomyeloneuropathy. AB - A 54-year-old patient with clinical and biochemical features of the adrenoleukomyeloneuropathy-complex is reported. Although CT was essentially normal, magnetic resonance (MR) showed areas of prolonged T1 and T2 values in the corpus callosum, around the trigones of the lateral ventricles, in the internal capsules, in the pons, and in the cervical spinal cord. This case report indicates that MR is better suited than CT to detect demyelination of the cerebral white matter and of descending tracts. PMID- 4019840 TI - MR imaging of cerebral toxoplasmosis: correlation of computed tomography and pathology. AB - A case of cerebral toxoplasmosis in a patient with acquired immune deficiency syndrome who was evaluated by both CT and magnetic resonance is reported. Magnetic resonance proved to be far more sensitive in detecting the intracranial lesions than CT. PMID- 4019841 TI - Low dose arterial contrast enhancement for cranial computed tomography in renal insufficiency. AB - In patients with severe renal insufficiency, the high iodine doses used for intravenous contrast medium enhanced CT can lead to renal injury. To minimize renal toxicity in one such patient, dynamic contrast enhanced CT was performed during right common carotid arterial infusion of 17 ml of 30% diatrizoate meglumine solution. Intense homogeneous contrast enhancement of an otherwise isodense mass permitted a diagnosis of meningioma, with excellent definition of tumor extent. PMID- 4019842 TI - Coexistence of a nasal mucoepidermoid carcinoma and sphenoid mucoceles: CT diagnosis and treatment implications. AB - Mucoepidermoid carcinomas of minor salivary gland origin rarely arise in the nasal cavity. A patient with such a tumor in association with bilateral sphenoid sinus mucoceles is presented. This diagnosis was established preoperatively by CT and allowed an attempt at curative surgery to be made. The CT and pathological findings are discussed. PMID- 4019843 TI - Papillary carcinoma in a thyroglossal duct cyst: CT findings. AB - A case of papillary carcinoma arising in a thyroglossal duct cyst is presented. The cystic mass may have a variable anatomic location: intralingual, suprahyoid, thyrohyoid, and suprasternal, along the course of the embryologic descent of the thyroid gland. Computed tomography allows characterization and precise identification of the extent of the lesion prior to surgical resection. PMID- 4019844 TI - Cardiac tumor associated with tuberous sclerosis: CT diagnosis. PMID- 4019845 TI - Jejunal perforation by a toothpick: CT demonstration. AB - Ingested foreign bodies are often seen in clinical practice, but their radiographic demonstration is unusual unless they have a metallic or bony density. This report describes and illustrates a case of small bowel perforation secondary to an ingested wooden toothpick and emphasizes the role of CT in evaluating similar cases. PMID- 4019846 TI - Delayed development of splenic subcapsular hematoma: CT evaluation. AB - We report a patient with delayed development of a splenic subcapsular hematoma following abdominal trauma. This unique occurrence may well explain the more commonly known phenomenon of delayed rupture of the spleen after trauma. PMID- 4019847 TI - Adenocarcinoma metastatic to the adrenal gland simulating myelolipoma: CT evaluation. AB - A case of metastasis to the adrenal gland is reported in which the CT appearance suggested myelolipoma by virtue of the presence of a discrete area of fat density within it. PMID- 4019848 TI - Enhanced ascites: CT sign of ureteral fistula. AB - Contrast enhancement of intraperitoneal fluid was observed on CT after intravenous contrast medium injection in a patient who had had a cesarean section 2 weeks earlier. Correct analysis of this finding led to prompt discovery of a clinically unsuspected partial right ureteral disruption by a hemostatic suture. At surgery the diagnosis was confirmed and the ureter repaired. PMID- 4019849 TI - CT diagnosis of intracranial neurinoma of the hypoglossal nerve. PMID- 4019850 TI - Computed tomography of metastatic chondrosarcoma to the brain. PMID- 4019851 TI - Aneurysmal dilatation of the superior mesenteric vein: CT findings. PMID- 4019852 TI - CT demonstration of a ureteroinguinal hernia causing hydronephrosis. PMID- 4019853 TI - CT signs of ischemic muscle necrosis. PMID- 4019854 TI - Respiratory ordered phase encoding (ROPE): a method for reducing respiratory motion artefacts in MR imaging. AB - A method of reducing respiratory artefact when using the spin warp technique of magnetic resonance imaging is described. A respiratory signal is used to determine the order in which the rows of the data matrix are measured. The aim is to make the respiratory signal at the time of each phase encoding gradient a slowly varying function of the time integral of the gradient and hence of the row number. Data are collected during each cycle of the imaging sequence; thus the scanning time is not increased. PMID- 4019856 TI - Practical skin pathology course. London, England, July 7-10, 1985. PMID- 4019855 TI - Fast overlapping scans in cerebral computed angiotomography. AB - Three to four overlapping cerebral CT scans were obtained after the injection of a single bolus of contrast medium. The rapid sequential dynamic scanning was carried out with table increments, while there was peak iodine density in the carotid artery. The demonstration of cerebral vessel lesions (aneurysms, moyamoya disease, arteriovenous malformations, arterial narrowing, etc.) is easier and safer with this method as compared with the conventional multiple injection technique. PMID- 4019857 TI - Hair follicle tumors of the skin. PMID- 4019858 TI - Sebaceous tumors of the skin. PMID- 4019859 TI - The natural history of nevus sebaceus. PMID- 4019860 TI - Pseudo-carcinomatous hyperplasia. PMID- 4019861 TI - Malignant epidermal tumours. PMID- 4019862 TI - Cutaneous metastases. PMID- 4019863 TI - Malignant melanocytic tumours. PMID- 4019864 TI - Borderline melanocytic tumors. PMID- 4019865 TI - Early diagnosis of Mycosis fungoides: vacuolar interface dermatitis. AB - The earliest detectable histologic alteration in patients developing mycosis fungoides is vacuolar interface dermatitis. Effacement of the epidermis is common. This is followed sequentially by invasion of the epidermis by mononuclear cells both singly and in groups, epidermal hyperplasia and finally the development of easily recognized Pautrier microabscesses as well as of characteristic atypical "mycosis" cells. PMID- 4019866 TI - The lichenoid tissue reaction. PMID- 4019867 TI - Follicular and perforating disorders. AB - Pathologic changes associated with hair follicles include infundibular hyperkeratosis, inflammation, mucinous degeneration and transepidermal elimination of foreign material. Because of the focal nature of the pathologic changes multiple sections are often useful in establishing the correct diagnosis. PMID- 4019868 TI - Necrobiotic granulomas. PMID- 4019869 TI - Mycobacterial skin infections. PMID- 4019870 TI - Cutaneous mucinous deposits. AB - A survey of conditions with mucinous deposits is given. The most important factors for their diagnosis are to consider these disorders and to stain the slides for proteoglycans or glycosaminoglycans; the most common routine techniques are the Giemsa and the Alcian-blue stain. More sophisticated methods allow differentiation between specific compounds, especially hyaluronic acid and various proteoglycans. PMID- 4019871 TI - Collagen diseases. AB - Dermatomyositis and variants of lupus erythematosus share histopathologic features which include liquefaction degeneration of the epidermal basal zone, melanin pigment incontinence, and the presence of colloid bodies. The pattern of epidermal changes and dermal inflammation help establish the correct diagnosis. Immunofluorescence microscopy of skin biopsies is useful in confirming the diagnosis. PMID- 4019872 TI - Panniculitis. PMID- 4019873 TI - Cutaneous vasculitis. PMID- 4019874 TI - Youth unemployment: a review of the literature. AB - This paper sets out to review the studies on youth unemployment conducted in a range of English speaking countries: America, Australia and Great Britain. The studies have been divided into six sections: psychological adjustment, attributions and expectations, education about unemployment, job choice and work experience, values, and job interview training. The paucity of good studies in this area partly explains the lack of clear replicated findings or coherent theories for the causes, correlates and consequences of unemployment among young people, though this is an area of relevance to social policy. Furthermore, it was concluded that various factors such as individual differences, salient demographic variables and previous work experience have been neglected. Nevertheless, many of the studies seem to indicate the presence of a destructive vicious circle which young people experience when failing to get a job: stress and disappointment, leading to lowered self-esteem, a change in expectations, and minor psychiatric illnesses which handicap the job search and application process so making unemployment all the more likely. PMID- 4019875 TI - Parent-adolescent communication. AB - This project involved the development of a questionnaire for measuring parent adolescent communication on both process and content dimensions. The six process dimensions, chosen on the basis of available literature, were: frequency, initiation, recognition, self-disclosure, domination and satisfaction. Six-point scales with clearly defined scale points were designed for each dimension. Fourteen content areas were also chosen and these were selected to include areas representative of two dimensions: general principles vs. specific issues, and external social reference vs. intrafamily references. First-year university students rated their interactions with their mothers, fathers and both parents together on each of the six process dimensions for each of the fourteen content areas. Parents were asked to rate the same items in the way they thought their adolescent son or daughter would rate them. Results were analysed separately for each process dimension using discriminant analysis, with sex of parent and sex of adolescent as independent variables. Overall, adolescents of both sexes tended to communicate more with mothers than with fathers over a wide range of areas. In fact, politics was the only area on which subjects talked more with fathers than mothers. Also, more self-disclosure occurred to mothers than to fathers, with daughters disclosing more to mothers than did sons. Mothers were also more accurate than fathers at predicting adolescents' responses. The usefulness of the questionnaire for exploring this important area of parent-adolescent communication will be discussed. PMID- 4019876 TI - Youth violence directed toward significant others. AB - This study explored violent behavior of high school students toward their parents, using a self-report questionnaire. The families of the students were characterized as having high, moderate, or low levels of family functioning, and these levels were correlated with the amount of violent behavior manifested by the youths. It was found that violence by young people toward their parents tended to be concentrated in households with strong manifestations of intra family violence or aggression between the parents, between parents and children, and between siblings. Low levels of family functioning, characterized by disagreements over money matters, inappropriate disciplining of children, few share activities, and alcohol abuse, also correlated strongly with youth violence toward parents. It was also found that youths involved in deviant peer group activity had higher levels of violence toward parents than youths who were not involved in this way. PMID- 4019877 TI - Adolescent perceptions of family scapegoating: a comparison of parental and sibling involvement. AB - A self-report measure of being scapegoated in one's family was given to a non clinical sample of 403 adolescents. Reports of scapegoating varied more with the type of family conflict scapegoated than with the family member(s) engaged in scapegoating. Scapegoating was also related to parental support, family conflict and adolescent adjustment problems. PMID- 4019878 TI - The sex distribution of children in care. AB - It is shown that there is a substantial and sustained disparity, both on a national and on a regional basis, between the numbers of males and the numbers of females in care. The disparity is analysed by examining the reasons for entering care, and the legal status of those in care. It is shown that in the aggregate the disparity is caused by imbalances in admissions, particularly in certain key legal and administrative categories. The phenomenon is also shown to have both geographical and accommodation dimensions, and some conjectures for its behavioural origins are offered. PMID- 4019879 TI - Characteristics of the psychoses of late onset in children and adolescents (a comparative study of hallucinating children). AB - In a retrospective design, 20 children and adolescents with psychoses of late onset and hallucinations were compared with 20 children with conduct or emotional disorders who also had hallucinations. Marked differences emerged between the two groups. Psychotic subjects showed significantly more delusions, abnormalities in language production, inappropriate affect, bizarre behaviour, hypoactivity, and social withdrawal. Some subjects had symptoms which indicated a specially profound breakdown in personality functioning, but schneiderian and other schizophrenic symptoms were relatively rare. This questions their diagnostic value in the psychoses of late onset of children and adolescents. PMID- 4019880 TI - Responses of high-producing dairy cows to long-term treatment with pituitary somatotropin and recombinant somatotropin. AB - Thirty Holstein cows capable of high milk production were utilized to examine the effects of long-term administration of bovine somatotropin on lactational performance. Treatments were 0 (control), 13.5, 27, and 40.5 mg/day of recombinantly-derived bovine somatotropin and 27 mg/day of pituitary-derived bovine somatotropin. Hormone was injected intramuscularly, once daily beginning at 84 +/- 10 days postpartum and continuing for 188 days. Cows were fed ad libitum a total mixed diet throughout the lactation. Recombinant somatotropin treatments increased average fat-corrected milk yield in a dose-dependent fashion from 23 to 41% over the control production (27.9 kg/day. Pituitary somatotropin (27 mg/day) increased milk production by 16%. Milk lactose, protein, and fat composition was similar for all treatments. Control cows were in positive energy balance throughout the treatment period (4.7 Mcal net energy/day. Initially, the large increase in milk yield with somatotropin treatment caused cows to decrease in energy balance. However, voluntary intake gradually increased, and by week 10 of treatment all somatotropin treatment groups were in positive energy balance. Thus, the gain in body weight over the treatment period was similar for all groups, ranging from 17 to 22%. Gross lactational efficiency (milk per unit of net energy intake) was improved by exogenous somatotropin whether calculated as observed, corrected for body weight changes, or using the theoretical energy requirements for maintenance and milk production. Results are consistent with bovine somatotropin as a homeorhetic control that coordinates an array of physiological processes so that nutrients are partitioned for milk synthesis. PMID- 4019881 TI - Characterization of limestones and their effects in vitro and in vivo in dairy cattle. AB - Capacities of limestones of differing particle size to neutralize acid in vitro and to modify pH and utilization of feedstuffs in vivo were compared. Acid neutralization during pH-stat titrations was faster for fine than for coarse limestone, and mixed microbial cultures were more resistant to pH change when they contained fine calcium carbonate. Diets containing 25:75 corn silage to concentrates and .95% calcium from either coarse or fine limestone were fed to rumen-fistulated heifers. Total ruminal volatile fatty acid concentrations were higher for the fine limestone treatment. Ruminal volumes, dry matter disappearance, and ruminal fluid pH and dilution rate did not differ between fine and coarse limestone treatments. Ruminal fluid volume, osmolality, ratios of acetate to propionate, and concentrations of total volatile fatty acids were unaffected in rumen-fistulated Holstein cows fed 60:40 corn silage to concentrates and either .5% calcium (control) or 1.0% calcium from either coarse or fine limestone. Ruminal pH increased .07 to .10 units with limestone supplementation. Ruminal fluid dilution and particulate turnover rates were slower for the coarse limestone than the control treatment. Differences between coarse and fine limestones in vitro were observed under some conditions in vivo, but they were not consistent. PMID- 4019882 TI - Prediction of heifer transmitting ability from genetic evaluations of sire, dam, and maternal grandsire. AB - Estimated transmitting abilities for milk of 258,201 Holstein heifers from first lactations were regressed on sire's milk proof, maternal grandsire's milk proof, and either dam's estimated transmitting ability from milk in first lactation or dams's estimated transmitting ability from milk of all lactations. Effects of year of birth of dam, dam's estimated transmitting ability for milk from first lactation, for milk from all lactations, estimated transmitting ability for fat from first lactation or for fat from all lactations were determined by sorting data into deciles by each of these criteria and calculating partial regression coefficients within each decile. For data in deciles on dams's estimated transmitting ability for milk in first lactation, no further information was gained from all lactations. Partial regression coefficients from regression of heifer's estimated transmitting ability from first lactation on dam's estimated transmitting ability from first lactation, maternal grandsire's proof, and sire's proof were similar to approximate theoretical upper limits. The partial regression coefficient for dam's estimated transmitting ability from all lactations was much smaller than expected. Because regression on dam's estimated transmitting ability from first lactation resulted in weights more closely approximating theoretical upper limits than weights from regression on dam's estimated transmitting ability from all lactations, the use of the former is preferred to predict heifer's estimated transmitting ability from first lactation. PMID- 4019883 TI - Selecting for lactation curve and milk yield in dairy cattle. AB - Knowledge of genetic relationships between characteristics of lactation curves and lactation yields is essential for joint selection for both. An equation, yt = atbexp(-ct), was chosen to depict individual lactation curves for 5,927 first lactations by Holsteins in 557 herds in Michigan Dairy Herd Improvement where yt is daily milk yield at day t in lactation, a is yield at time zero, b is ascent to peak, and c is decline after peak. Genetic correlations for 305-day milk yield with initial production (a), ascent to peak (b), descent after peak (c), and peak yield were -.37, .40, 0, and .91. From empirical results from applied selection indexes, selecting for both increase of ascent to peak and peak yield did not decrease 305-day milk substantially. Rankings of sires on these indexes were similar to their rankings on milk yield alone. Attempts to decrease peak yield and increase persistency decreased milk yield greatly. PMID- 4019884 TI - Genetic and phenotypic statistics of lactation cell counts in different lactations of Holstein cows. AB - Between February 1977 and February 1982, 680,246 monthly test-day observations of somatic cell count were taken for Holstein cows having completed 79,124 lactations in 941 herds on the Quebec Dairy Herd Analysis Service. Data were transformed to natural log scale, and analyses were separate within five parity groups. Two lactational measures of cell count, geometric mean, and weighted (by test-day milk yield) mean of the log of monthly cell counts were calculated for each lactation. Maximum likelihood, iterative Minimum Norm Quadratic Unbiased Estimation, and multivariate Restricted Maximum Likelihood procedures were used for estimation of genetic and phenotypic parameters. Repeatabilities of log test day cell counts and log of test-day cell counts corrected for milk yield were the same at each parity, .36, .41, .42, .42, and .42 in first, second, third, fourth, and fifth and later parities. Repeatabilities of lactational measures of cell count were .33 between first and second parities, .40 between second and third parities, .13 between first and third parities, and .27 between first, second, and third parities. Heritabilities of measures of lactational cell count were small from .06 to .14 in the five parities. Genetic correlations between measures of lactational cell count in different parities were close to unity, .90 to .97. PMID- 4019885 TI - Effect of season and high environmental temperature on fertility of Holstein cattle. AB - The breeding records and meteorological data for cows with first services between July 1, 1979, and June 30, 1980, in a large Florida herd were analyzed to determine the relationship between temperature and breeding efficiency. Seasonal high environmental temperatures were associated with low breeding efficiency. Increased maximum temperature from 29.7 degrees C during April to 33.9 degrees C during July was associated with a decrease in conception rate on first service from 25 to 7%. Also, the average number of inseminations per conception, based on pregnancy diagnosis 6 to 8 wk after breeding, was higher from May to August (4.5 to 5.3) than from September to April (2.3 to 3.5). Days open were longer for the cows first inseminated during May, June, and July (173, 171, and 167 days, respectively) than during other months (99 to 149 days). Temperature decreases of any magnitude for 1 to 3 days before or after the day of breeding, when maximum temperatures on the day of breeding were greater than or equal to 27 degrees C, were associated with higher pregnancy rates. Also, similar temperature decreases around the time of breeding, below the previously mentioned high maximum temperatures for 20 days before the day of breeding, were accompanied by higher conception rates. Fertility was consistently lower under all temperature changes when maximum temperatures on the day of breeding were greater than or equal to 33 degrees C. PMID- 4019886 TI - Production and physiological responses of dairy cows to varying dietary potassium during heat stress. AB - Objectives were to study influences of heat stress and dietary potassium content on production and physiological responses of 8 Jersey and 10 Holstein cows blocked by breed and assigned randomly to no shade or shade environments. Each cow received a different dietary potassium treatment (.66, 1.08, and 1.64% of dry matter) in each of three 30-day periods. Rates of potassium loss from skin were almost five times greater for no shade as for shade cows during the hottest part of the day (1300 to 1500 h). Overall, cows with no shade ate 56% less during the daytime (0800 to 1600 h), 19% more during nighttime (1600 to 0800 h), and 13% less total feed than cows with shade. Interactions of environment and breed with dietary potassium treatment suggest differences in feed intake and milk yield responses to increasing dietary potassium content. Total daily feed intake and milk yield of cows with no shade responded in curvilinear fashion to increasing dietary potassium, whereas responses in shade were small. Largest responses in no shade were as dietary potassium increased from .66 to 1.08%. Milk yield of Holsteins increased with increasing dietary potassium, but yield of Jerseys did not. Combined effects of elevated potassium loss from skin and reduced potassium and dry matter intake during heat stress suggested that lactating dairy cows may benefit from supplemental potassium. PMID- 4019887 TI - Upper critical temperatures and forced ventilation effects for high-yielding dairy cows in a subtropical climate. AB - Upper limit of thermal stability and subsequent rise of thermoregulatory functions as affected by forced ventilation were examined. Rectal temperature, respiratory frequency, ear skin temperature, body weight, and milk yield were recorded biweekly July to March over 2 yr for 170 Israeli-Holstein cows (305-day milk yield 9000 kg/cow) at air temperatures 10 to 36 degrees C. Cows were in an open shelter. One side was force ventilated over 2.5 m along the stanchions (air velocity 1.5 to 3 m/s) from 0500 to 2200 h. Control side mean air velocity was .5 m/s. Within the 10 to 24 degrees C range, rectal temperature was not affected by air temperature or forced ventilation but increased by .02 degrees C/kg fat corrected milk in animals producing above 24 kg/day. Between 26 and 36 degrees C rectal temperature increased with air temperature in both groups; rate of rise was halved by forced ventilation. In this range of air temperature, rectal temperature increased with rising milk yield, as in the lower air temperature range, in both high-producing and lower-producing cows in forced ventilation. Body weight or parity did not have significant effects. Mean ear skin temperature was higher for control animals, but its rate of increase with air temperature was similar in both groups. Forced ventilation reduced mean respiratory rate. An upper critical temperature is 25 to 26 degrees C and is independent of milk yield or acclimatizational state of cows exposed to the natural sequence of climate. PMID- 4019888 TI - Survey of nutritional management practices and metabolic disorders in West Virginia dairy herds. AB - Sixteen farmers, representing three major dairy counties in West Virginia, were interviewed to determine current dairy management practices. Herd health records were used to determine the incidence of metabolic and digestive disorders. All feedstuffs used on these farms were sampled for chemical analyses. The total number of cows on the 16 farms surveyed was 1870 with an average herd size of 117 and 6387 kg milk produced per cow per year. Fourteen of the 16 farmers used forage testing services, obtained professional advice on feeding and nutrition, and attempted to feed according to production. Eleven of sixteen farmers increased grain 2 weeks prior to calving and all gradually adjusted the intake of grain to cows recently freshened. Ration imbalance problems included both excesses and deficiencies of energy, protein, phosphorus, and calcium. Excess calcium, phosphorous, and crude protein were correlated (P less than .01, r2 = .74) with the incidence of fat cows. The incidence of metabolic disorders in these herds was low to average and the most prevalent management problem encountered was low butter fat. PMID- 4019889 TI - Changes of evaluation for natural-service sampled bulls brought into artificial insemination. AB - United States Department of Agriculture Sire Summary files were used to select bulls with a published Modified Contemporary Comparison sire evaluation prior to entry into artificial insemination. Canadian bulls were not included. Of the Brown Swiss, Guernsey, Holstein, and Jersey bulls that entered artificial insemination since 1974, 28 Brown Swiss, 19 Guernseys, 298 Holsteins, and 45 Jerseys (4 to 12%) had natural service evaluations. Of these bulls, 10 Guernseys, 154 Holsteins, and 28 Jerseys had an increase of Repeatability of 30% or more after entering artificial insemination. Evaluations for bulls just prior to their entering artificial insemination were compared with their most recent evaluations through July 1983. Average Repeatabilities for evaluations of bulls just prior to their entering artificial insemination were 32% for Guernseys, 32% for Holsteins, and 31% for Jerseys and 88, 90, and 87% for their most recent evaluations. Average Predicted Differences prior to entering artificial insemination were 305 kg for Guernseys, 394 kg for Holsteins, and 452 kg for Jerseys for milk and 11, 10, and 16 kg for fat. Most recent average Predicted Differences were 268, 380, and 532 kg for milk and 7, 10, and 18 kg for fat. Predicted Differences of natural service bulls were not overevaluated regardless of number of herds for sampling or year of entry into artificial insemination. Artificial insemination organizations can continue to acquire bulls with natural service evaluations calculated with the Modified Contemporary Comparison and be confident that these Predicted Differences are not overestimated. PMID- 4019890 TI - Environmental mastitis: cause, prevalence, prevention. AB - Rate of intramammary infection by coliform bacteria and species of streptococci other than Streptococcus agalactiae (environmental pathogens) was studied in a dairy herd in total confinement. Rate was higher during the dry period than during lactation and increased progressively as parity increased. Rate was maximal during summer and coincided with maximum exposure to coliforms in bedding. Streptococcal infections were longer than coliform. Approximately 59% of streptococcal infections and 69% of coliform infections were present for 30 lactation days or less. Percent quarters infected by day of year varied between .7 and 3.0% for coliform bacteria and between 1.6 and 4.7% for streptococci. Approximately 81% of coliform infections and 53% of streptococcal infections during lactation were clinical. Clinical cases were highest during the first 76 days of lactation and during summer. Only 6.7% of coliform infections resulted in acute coliform mastitis, and all acute cases were during summer or early lactation. Dry cow therapy reduced rate of streptococcal infection during the early dry period but was without effect during the prepartum period. There was no effect of dry cow therapy on coliform infection rate during the dry period. Problems associated with prevalence and control of environmental mastitis were discussed. PMID- 4019891 TI - Proceedings of the Second World Congress on Cancers of the Skin. March 7-9, 1985, New York City. Abstracts. PMID- 4019892 TI - [Cellular cholinesterases of epidermis and skin glands of mammals]. PMID- 4019893 TI - [Effect of immunoglobulins on work capacity of irradiated animals]. PMID- 4019894 TI - [Numerical model of lymphocyte population in animals in normal state and in lymphocytic leukemia]. PMID- 4019895 TI - [Polymorphism of arylamine acetyltransferase and monooxygenase participating in metabolism of aromatic amines]. PMID- 4019896 TI - [Effect of finely-dispersed iron powder on the development of iron deficiency anemia]. PMID- 4019897 TI - Asymptotic analysis of a viscous cochlear model. AB - A model of cochlear macromechanics, involving a viscous cochlear fluid, is analyzed asymptotically for slowly varying membranes. The results exhibit the effect of viscosity on the amplitude, wavelength, and damping rate, and confirm the conclusion that viscosity is not important. However the method can be used on other models, such as those of cochlear micromechanics, where viscosity is more important. PMID- 4019898 TI - Cochlear nucleus, inferior colliculus, and medial geniculate responses during the behavioral detection of threshold-level auditory stimuli in the rabbit. AB - Rabbits were conditioned to respond behaviorally to auditory stimuli by pairing a white-noise conditioned stimulus (CS) with a corneal airpuff unconditioned stimulus (US). The conditioned response (CR) was movement of the nictitating membrane (NM). After the subjects were responding at better than the 90% correct level, the intensity of the auditory stimulus was reduced to behavioral threshold using a staircase procedure. Simultaneous measurements of neural unit activity and behavioral NM responses were then made in rabbits performing at behavioral threshold. After the experiment was completed neural unit responses during behavioral detection trials were compared to neural responses made during nondetection trials. Neural unit responses to a constant intensity, white-noise stimulus at behavioral threshold were well defined and essentially identical on behavioral detection and nondetection trials in the ventral cochlear nucleus, the ventrolateral division of the central nucleus of the inferior colliculus, and the ventral division of the medial geniculate body. This suggests that an auditory stimulus can be neuronally "detected" without being behaviorally detected, and that the neural "decision" to respond behaviorally is not made in these nuclei. Responses recorded from the dorsomedial division of the central nucleus of the inferior colliculus, the pericentral nucleus of the inferior colliculus, and less commonly in the medial division of the medial geniculate body were also clearly present and nearly identical during the onset of the auditory stimulus, but were sometimes consistently different for detection and nondetection conditions during the latter part of the auditory stimulus. These brain regions appear to receive both auditory and nonauditory inputs, and show responses which are more highly correlated with detection behavior. PMID- 4019899 TI - A power-law transformation predicting masking by sounds with complex spectra. AB - In a previous paper [R. Lutfi, J. Acoust. Soc. Am. 73, 262-267 (1983)], the following rule was proposed for predicting masking by pairs of simultaneous maskers; Xab = [XPa + XPb]1/P, where in units of power, Xa and Xb are the individual masking effects of the maskers, Xab is the combined effect, and 0.20 less than or equal to p less than or equal to 0.33. In this paper, the rule is used to predict the results of studies in the literature that have measured masking by sounds with various other complex spectra. In most of these studies, the individual maskers comprising the complex have nominally nonoverlapping power spectra. A single value of p = 0.33 yields predictions in good agreement with the data of these studies. For a study in which the component maskers overlap more appreciably, a larger value of p = 0.50 produces equally accurate predictions. The rule also predicts some general features of the results of studies in which the individual effects of the maskers in the complex are not known but can be estimated. It is suggested that the general applicability of the rule reflects a conjoint analysis by the auditory system of two or more waveform statistics. PMID- 4019900 TI - The danger of using narrow-band noise maskers to measure "suppression". AB - These experiments investigated whether perceptual cueing plays a role in the "unmasking" effects which have been observed in forward masking for narrow-band noise maskers and brief signals. The forward masking produced by a 100-Hz-wide noise masker at a level of 60 dB SPL was measured for a 1-kHz sinusoidal signal with a raised-cosine envelope and a duration of 10 ms at the 6-dB-down points, both for the masker alone, and with various components added to the masker (and gated synchronously with the masker). Unmasking was found to occur even for components which were extremely unlikely to produce a significant suppression of the masker: these included a 75-dB SPL 4-kHz sinusoid, a 50-dB SPL 1.4-kHz sinusoid, a noise low-pass filtered at 4 kHz with a spectrum level of 0 dB, and a noise low-pass filtered at 4 kHz with a spectrum level of 20 dB presented in the opposite ear to the masker-plus-signal. It is concluded that perceptual cueing can play a significant role in producing unmasking for brief signals following narrow-band noise maskers, and that it is unwise to interpret the unmasking solely in terms of suppression. PMID- 4019901 TI - Acoustical aspects of contrastive stress in question-answer contexts. AB - A series of experiments was conducted to examine the influence of contrastive stress on intonational patterns of duration and fundamental voice frequency (F0). In a preliminary study, intonational patterns in spontaneous speech were compared with the patterns in oral reading of the transcribed spontaneous material. In both circumstances, a general declination of F0 peaks throughout the course of a sentence was not regularly observed, contrary to earlier findings with oral reading of isolated sentences. Two experiments were then conducted to examine the possibility that the general absence of declination observed here might be due to the influence of sentence focus, following previous results from Swedish showing that declination was not observed consistently in isolated sentences until after the site of focus. In experiment 1, we found no evidence of this restriction on declination in the oral reading of English declaratives. Declination was observed both before and after the focused item in a sentence. Furthermore, our analyses revealed that focus (as manifested by contrastive stress) is generally accompanied by an increase in duration on the focused word and by a sharp drop in F0 following the focused item. In experiment 2, these effects were replicated and extended using longer sentences. In both experiments, the influence of focus was strictly localized to the site of focus in the case of duration, but not F0. The results for both duration and F0 indicate that the influence of focus assignment on these attributes varies systematically as a function of the focus location in the sentence. Finally, the combined elongation effects for focus and utterance final lengthening were less than would be predicted by an additive model, suggesting the operation of an expandability constraint on segmental lengthening in speech production. PMID- 4019902 TI - Temporal summation by Pacinian corpuscles precludes entrainment at the detection threshold. AB - For rapidly adapting mechanoreceptor afferents, entrainment is defined as a response of one spike per stimulus cycle. For Pacinian corpuscles, the entrainment threshold and psychophysical detection threshold are similar. The psychophysical threshold, however, exhibits temporal summation, which proves that the psychophysical threshold and the physiological entrainment threshold cannot be identical. PMID- 4019903 TI - Click stimuli do produce masking-level differences, sometimes. PMID- 4019904 TI - Acoustics of a standing wave tank for studying the hearing capacity of fish. AB - In a standing wave tank responses of fish to sound stimuli used to investigate the hearing capacity of fish may perhaps be affected by unintended stimulation of the lateral line. Uniform oscillatory water flow patterns do not stimulate the lateral line. Departures from uniformity were derived from measurements to acoustic pressure and particle velocity at 5-cm spacings around the center in our standing wave tank containing six transducers suspended along three axes that are perpendicular to one another. These measurements are compared with the results of a model in which negligible influence of the tank wall and an incompressible water column in the tank are assumed. Deviations of computed values from measured values of sound pressure and the principal velocity components are less than 5 dB. The model underestimates velocity components perpendicular to the principal component. However, the model does appear a reliable aid for estimating the spatial function of sound pressure and velocity from the values of p and v measured at the tank center. Upper limits for the relative velocities between the fish body and the water can only approach threshold values for the lateral line stimulation under worst conditions (i.e., a velocity node at the tank center) in this setup. PMID- 4019905 TI - The effect of the player's vocal tract on woodwind instrument tone. AB - Many players of woodwind instruments believe that the tone of the instrument is influenced by the player's vocal tract. If this is so, it would be expected that the vibrating reed in the player's mouth would generate an appreciable sound pressure in his vocal tract. However, measurements of the vocal tract impedance (looking into the mouth) give values an order of magnitude less than the impedances of the clarinet air column resonances. The sound pressure built up in the vocal tract would thus be expected to be much smaller than that in the clarinet. A clarinetlike system was arranged to sound by drawing air through it from the normally open end, the reed being out in the open for easy accessibility. When the mouth was placed around the mouthpiece with the system sounding, the changes in the waveform and harmonic structure of the tone were minimal. When a system with a more sharply tuned resonance was substituted for the vocal tract, the waveform changes were observable but not large. It appears that the player's vocal tract has a negligible influence on the instrument tone. PMID- 4019906 TI - Acoustic characteristics of perceived versus actual vocal age in controlled phonation by adult females. AB - The purpose of this investigation was to obtain information on the acoustic characteristics of women's voices as a function of perceived versus actual age. Tape recordings of whispered and normally phonated /ae/ vowels were obtained from 75 women in three age groups (25-35, 45-55, and 70-80 years). One-second segments of phonemically representative /ae/ vowels were played to 23 listeners for relative age judgments. Phonated vowel productions were analyzed in terms of mean fundamental frequency, fundamental frequency standard deviation, and jitter ratio, as well as F1 and F2 frequencies. Whispered vowels were analyzed only in terms of F1 and F2 frequencies. Multiple regression analysis revealed that older age judgments based on phonated vowels were significantly associated with higher fundamental frequency standard deviation values and lower mean fundamental frequency values. Older age judgments based on whispered vowels were significantly associated with lower F1 frequencies. Results of this investigation suggest that both phonatory and resonance features play a role in defining age characteristics of women's voices. Acoustic cues associated with perceived age generally agreed with acoustic findings as a function of actual age. PMID- 4019907 TI - Constancy of (acoustic) relative timing measures in phrase-level utterances. AB - The hypothesis that acoustic measures of relative speech timing remain constant across large changes in speaking rate was tested for fluent utterances produced by normal and neurogenically disordered speakers. For all speakers, relative timing tended to be statistically invariable across conversational and fast speaking rates. This finding was considered especially interesting in the case of speakers with dysarthria and apraxia of speech, because absolute measures of speech timing associated with these disorders are typically aberrant. A post hoc analysis of relative variability across speakers showed the ratio measures to be consistently less variable than measures of absolute interval duration. The greater similarity across speakers of ratio measures, as compared to interval measures, was taken to mean that characterizing the temporal structure of articulatory sequences in terms of relative timing is an appropriate way to capture an important aspect of the biological constraints associated with speech production. PMID- 4019908 TI - Ultrasonic absorption of bovine serum albumin solutions in the frequency range 200 kHz-1 MHz. AB - The ultrasonic absorption of solutions of two electrolytes, magnesium and manganous sulfates, and also of the globular protein bovine serum albumin, has been measured using small volume spherical resonators at frequencies in the range 200 kHz-1.2 MHz. The principles of the technique are discussed and absorption values obtained for the electrolyte solutions at 20 degrees C are compared with existing values using other methods. For BSA, measurements were made at 8 degrees C over a range of pH values. Under both acid and alkaline conditions, excess losses at megahertz frequencies were found to persist down to at least 200 kHz. A new loss peak at approximately 400 kHz has been found at pH 3.2. PMID- 4019909 TI - Differential sensitivity to tonal frequency and to the rate of amplitude modulation of broadband noise by normally hearing listeners. AB - Differential sensitivities for tones which varied in frequency (containing cues for place and periodicity) and for broadband noise which varied in the rate of sinusoidal amplitude modulation (presumably containing only a periodicity cue) were measured at common frequencies and modulation rates of the stimulus for four normally hearing listeners. A forced-choice adaptive psychophysical procedure was used in all measurements. Through 60 Hz, tonal-frequency and rate discrimination were similar (on average, 2.5-3.0 Hz) across listeners. From 80-400 Hz, differential sensitivity for tones was between 1.0 and 2.0 Hz, whereas values for rate discrimination increased almost linearly from about 3.6 to 122.0 Hz. Apparently, differential sensitivities for both tonal frequency and modulation rate are mediated similarly, presumably by the same (periodicity) mechanism, through 60 Hz. Above 60 Hz, the listener is more sensitive to differences in tonal frequency than modulation rate. Detection thresholds for sinusoidal amplitude modulation of noise also were measured for these listeners. An average modulation threshold function was obtained and a half-power frequency was estimated for the function at 60 Hz; from this value a time constant of 2.65 ms may be derived, which is consistent with time constants measured by other psychophysical methods. These data further point to some change in perceptual quality above about 60 Hz, that frequency above which we found tonal-frequency and rate discrimination functions to separate. PMID- 4019910 TI - A scale for rate of tactual vibration. AB - Observers were asked to make estimates of the rate of mechanical vibrations presented to the finger as pulses ranging from 2 to about 300 pps. From the functions generated by this study, a set of ten values of mechanical vibration rate was selected. In a second experiment additional observers were asked to learn to identify these values of rate. Information analysis of the data showed that, when rate alone is varied, observers can identify between three and five items correctly; when rate and intensity are covaried redundantly, between five and eight items can be identified correctly. These results are viewed as supporting those from studies of the DL for rate, and as evidence for a limited but useful role of rate discrimination in tactile displays of acoustic signals. PMID- 4019911 TI - Effect of opening and draining the cochlea. AB - The WKB approximation was used in calculations of the pure-tone response of a two dimensional inviscid model of the human cochlea and a three-dimensional inviscid model of the guinea pig cochlea. The common experimental procedure of opening the scala tympani was simulated. Basilar membrane displacement was unaffected at and beyond the peak, but was slightly lower pre-peak. The peak location shifted to a significant extent apically only when the fluid level in the scala tympani was lowered to less than 1/10 of normal depth. PMID- 4019912 TI - A survey of indoor air monitoring services: is there a private demand for healthful indoor air quality? PMID- 4019913 TI - A pilot indoor-outdoor study of organic particulate matter and particulate mutagenicity. PMID- 4019914 TI - Silent myocardial ischemia: hemodynamic changes during dynamic exercise in patients with proven coronary artery disease despite absence of angina pectoris. AB - The hemodynamic changes during exercise occurring in 36 patients with proven coronary artery disease (10 without and 26 with previous myocardial infarction) who tolerated the stress test without angina were analyzed and compared with changes observed in a control group of 36 carefully matched patients whose exercise was limited by angina. All patients were exercised to the same extent, reaching a similar rate-pressure product at the end of the stress test (19,508 +/ 4,828 [SD] versus 19,247 +/- 4,117 beats/min X mm Hg [NS] in the study and control groups without prior infarction, and 19,665 +/- 3,950 versus 17,701 +/- 4,600 beats/min X mm Hg [NS] in the respective groups with infarction). In all groups left ventricular end-diastolic pressure increased from rest to exercise (from 18 +/- 4 to 36 +/- 11 and from 13 +/- 5 to 29 +/- 9 mm Hg, respectively, in the study and control groups without prior infarction and from 17 +/- 7 to 32 +/- 13 and from 19 +/- 7 to 36 +/- 9 mm Hg in the respective groups with prior infarction). Left ventricular ejection fraction decreased (from 59 +/- 7 to 50 +/ 15 and from 60 +/- 4 to 52 +/- 9% in the study and control groups without prior infarction and from 54 +/- 9 to 47 +/- 10 and 55 +/- 9 to 50 +/- 4% in the respective groups with prior infarction). Whereas the changes from rest to exercise were highly significant within each group, no significant differences were noted between the corresponding groups. Regional de novo hypokinesia appeared in all patients without prior infarction and in 25 and 22 patients, respectively, of the groups with prior infarction. Thus, under similar physical stress conditions, comparable hemodynamic changes indicative of ischemia are observed in patients with significant coronary artery lesions with or without previous myocardial infarction irrespective of the occurrence of angina. Therefore, angina pectoris cannot be considered a prerequisite for hemodynamically significant ischemia during exertion. PMID- 4019915 TI - Angiographic occurrence and clinical correlates of intraluminal coronary artery thrombus: role of unstable angina. AB - The importance of intraluminal coronary artery thrombus in acute myocardial infarction is now recognized. Coronary thrombi, however, may be important in ischemic syndromes other than infarction. The coronary angiograms of 268 consecutive patients undergoing diagnostic angiography were prospectively examined for intracoronary thrombus and form the basis of this study. Of these patients, 29 (11%) (25 men and 4 women) met the criteria for coronary artery thrombus. Of the 29 patients with thrombus, 24 (83%) had unstable angina before angiography. The five remaining patients with thrombus had had a transmural myocardial infarction 3 to 18 months before cardiac catheterization. In 21 patients, the thrombus was distal to a significant stenosis; in 8 it was proximal to or at the site of a significant stenosis. Coronary artery thrombus was identified in 24 (35%) of 67 patients with unstable angina compared with only 5 (2.5%) of 201 patients with stable angina (p less than 0.0001). PMID- 4019916 TI - Significance of the pericardium in human subjects: effects on left ventricular volume, pressure and ejection. AB - To assess the effect of the pericardium, left ventricular systolic function and diastolic compliance were studied in 15 patients before and after pericardiotomy during coronary artery surgery. Using first pass radionuclide angiography, curves for left ventricular systolic function (stroke work versus end-diastolic volume) and a measure of diastolic compliance (pulmonary capillary wedge pressure versus end-diastolic volume) were generated by changing body position to alter venous return. Left ventricular end-diastolic volume ranged from 41 to 111 ml/m2 and pulmonary capillary wedge pressure from 0 to 24 mm Hg. No significant changes were found in blood pressure (150/83 to 148/82 mm Hg), heart rate (66.7 to 67.1 beats/min), cardiac index (2.38 to 2.41 liters/min per m2), ejection fraction (0.56 to 0.54), end-systolic volume index (31.4 to 32.2 ml/m2), end-diastolic volume index (65.9 to 69.5 ml/m2) or pulmonary capillary wedge pressure (7.5 to 7.3 mm Hg). The pericardium did not affect the curves relating stroke work and end-diastolic volume or those relating pulmonary capillary wedge pressure and end diastolic volume. Thus, when filling pressure and volume are normal or only moderately elevated, the pericardium does not appear to affect left ventricular systolic function or diastolic compliance in patients. PMID- 4019917 TI - Threshold of pericardial constraint: the pericardial reserve volume and auxiliary pericardial functions. PMID- 4019918 TI - Determinants of the outcome of electrophysiologic study in patients with ventricular tachyarrhythmias. AB - To determine those factors predictive of the ability to both initiate and suppress ventricular tachyarrhythmias during electrophysiologic study, the results of programmed cardiac stimulation were evaluated in 261 patients: 66 presenting with nonsustained ventricular tachycardia, 91 with sustained ventricular tachycardia and 104 with ventricular fibrillation. Multivariate logistic regression analysis revealed that the presenting arrhythmia was a potent and independent predictor of the ability to provoke ventricular arrhythmias at electrophysiologic study; a history of myocardial infarction and male sex were also significant independent predictors. Of patients presenting with sustained ventricular tachycardia, 89% (81 of 91) had inducible ventricular arrhythmias compared with 61 (40 of 66) and 66% (69 of 104) of patients with nonsustained ventricular tachycardia and ventricular fibrillation, respectively. Complete suppression of inducible arrhythmias could be achieved in only 52% (34 of 66) of patients with sustained ventricular tachycardia, compared with 73 (24 of 33) and 75% (46 of 61) of patients presenting with nonsustained ventricular tachycardia and ventricular fibrillation, respectively. Multivariate analysis showed that the major independent determinants of the ability to suppress inducible arrhythmias were the number of drug trials performed before electrophysiologic study (inversely correlated) and the nature of the induced arrhythmia. The nature of the presenting clinical arrhythmia is, therefore, a highly significant and independent predictor of the ability to induce ventricular arrhythmias during electrophysiologic testing and an important determinant of the ability to suppress induced arrhythmias in patients with spontaneous ventricular tachyarrhythmias. PMID- 4019919 TI - Retention and clearance of C-11 palmitic acid in ischemic and reperfused canine myocardium. AB - Free fatty acids are the major energy source for cardiac muscle. Oxidation of fatty acid decreases or even ceases during ischemia. Its recovery after transient ischemia remains largely unexplored. Using intracoronary carbon-11 palmitic acid as a tracer of myocardial fatty acid metabolism in an open chest dog model, retention and clearance of tracer in myocardium were evaluated at control, during ischemia and after reperfusion following a 20 minute occlusion of the left anterior descending coronary artery. Myocardial C-11 time-activity curves were analyzed with biexponential curve-fitting routines yielding fractional distribution and clearance half-times of C-11 palmitic acid in myocardial tissue. In animals with permanent occlusion and intracoronary injection of C-11 palmitic acid distal to the occlusion site, the relative size and half-time of the early clearance curve component differed markedly from control values and did not change with ongoing ischemia. Conversely, in animals with only 20 minutes of coronary occlusion, the relative size of the early C-11 clearance phase was still significantly depressed at 20 and 90 minutes of reperfusion but returned to control level at 180 minutes. Tissue C-11 clearance half-times remained significantly prolonged throughout the reperfusion period. Regional function in reperfused myocardium monitored with ultrasonic crystals recovered slowly and was still less than control after 3 hours of reperfusion. The data indicate that after transient ischemia, myocardial fatty acid metabolism fails to recover immediately. Because the metabolic recovery occurs in parallel with recovery of regional function, C-11 palmitic acid in conjunction with positron tomography may be useful for studying regional fatty acid metabolism noninvasively after an ischemic injury, and may be helpful in identifying reversible tissue injury. PMID- 4019920 TI - Synchronized diastolic coronary venous retroperfusion: results of a preclinical safety and efficacy study. AB - The safety and efficacy of a new clinical synchronized diastolic retroperfusion mechanical pump and autoinflatable balloon catheter was studied in 10 dogs during and after 6 hours of left anterior descending coronary artery occlusion. Eight other dogs served as the untreated control group. Infarct size measured by triphenyltetrazolium chloride, and expressed as a percent of area at risk, was significantly reduced by retroperfusion treatment (19 +/- 18 versus 58 +/- 36, p less than 0.01). Morphologic examination of the coronary sinus and cardiac veins did not demonstrate evidence of damage from synchronized retroperfusion. There was also no evidence of excess myocardial edema in either the jeopardized ischemic or normally perfused zones. There was no evidence of significant red cell hemolysis or platelet destruction from the treatment. Thus, it appears that synchronized diastolic retroperfusion is a safe and effective treatment of acute myocardial ischemia in experimental animals and warrants clinical testing. PMID- 4019921 TI - Quantitative assessment of pulmonary hypertension in patients with tricuspid regurgitation using continuous wave Doppler ultrasound. AB - Doppler ultrasound examination was performed in 69 patients with a variety of cardiopulmonary disorders who were undergoing bedside right heart catheterization. Patients were classified into two groups on the basis of hemodynamic findings. Group I consisted of 20 patients whose pulmonary artery systolic pressure was less than 35 mm Hg and Group II consisted of 49 patients whose pulmonary artery systolic pressure was 35 mm Hg or greater. Tricuspid regurgitation was detected by Doppler ultrasound in 2 of 20 Group I patients and 39 of 49 Group II patients (p less than 0.001). Twenty-six of 27 patients with pulmonary artery systolic pressure greater than 50 mm Hg had Doppler evidence of tricuspid regurgitation. In patients with tricuspid regurgitation, continuous wave Doppler ultrasound was used to measure the velocity of the regurgitant jet, and by applying the Bernoulli equation, the peak pressure gradient between the right ventricle and right atrium was calculated. There was a close correlation between the Doppler gradient and the pulmonary artery systolic pressure measured by cardiac catheterization (r = 0.97, standard error of the estimate = 4.9 mm Hg). Estimating the right atrial pressure clinically and adding it to the Doppler determined right ventricular to right atrial pressure gradient was not necessary to achieve accurate results. These findings indicate that tricuspid regurgitation can be identified by Doppler ultrasound in a large proportion of patients with pulmonary hypertension, especially when the pulmonary artery pressure exceeds 50 mm Hg. Calculation of the right ventricular to right atrial pressure gradient in these patients provides an accurate noninvasive estimate of pulmonary artery systolic pressure. PMID- 4019922 TI - Increasing importance of Doppler echocardiography. PMID- 4019923 TI - A possible increase in the incidence of congenital heart defects among the offspring of affected parents. AB - The incidence of congenital heart disease in the children of 219 probands was determined. Each of these probands had one of four selected defects: atrial septal defect, coarctation of the aorta, aortic valve stenosis or complex dextrocardia. Of their children, 8.8% had substantial congenital cardiac defects. This is a much higher incidence than that reported in most comparable studies. The difference is highly significant statistically and therefore is likely to be genuine. The cause of the high recurrence is probably environmental. PMID- 4019924 TI - Two-dimensional echocardiographic findings in double orifice mitral valve. AB - Between December 1981 and April 1984, five children ranging in age from 1 month to 5 1/2 years examined by two-dimensional echocardiography appeared to have a double orifice mitral valve. The diagnosis was verified in one patient at surgery, one patient by angiography and one patient by necropsy. Associated malformations included mitral stenosis and regurgitation, coarctation of the aorta, ostium primum and secundum atrial septal defect, ventricular septal defect and hypoplastic left heart syndrome. Three varieties of double orifice mitral valve were observed: an incomplete bridge type (one patient), in which a small strand of tissue connected the anterior and posterior leaflets at the leaflet edge level; a complete bridge type (three patients), in which a fibrous bridge divided the atrioventricular orifice completely into equal or unequal parts and a hole type (one patient), in which an additional orifice with subvalvular apparatus occurred in the posterior commissure of the mitral valve. These three types could be distinguished by sweeping the transducer in cross-sectional view from the apex toward the base of the heart. Both orifices could be seen throughout the scan in the complete bridge type while in the incomplete bridge type the two orifices could be seen only at the level of the papillary muscles. In the hole type, the second orifice was seen at about midleaflet level. In all three types, the chordae surrounding each orifice attached to only one papillary muscle. Congenital mitral stenosis or regurgitation was evident in three patients. The type of the double orifice mitral valve did not predict the presence or severity of symptoms. PMID- 4019925 TI - Two-dimensional echocardiographic evaluation of right ventricular size and function in newborns with severe right ventricular outflow tract obstruction. AB - Critical pulmonary stenosis or atresia with intact ventricular septum represents a congenital cardiac lesion for which the long-term prognosis appears to depend partly on the size of the right ventricle. Thus, the capability of noninvasive assessment of right ventricular size to predict operative outcome was examined in 15 infants (aged 1 to 30 days, mean 5.6) with severe right ventricular outflow tract obstruction (either critical pulmonary stenosis [7 patients] or pulmonary atresia with intact ventricular septum [8 patients]). Using echocardiography in two orthogonal subxiphoid views, right ventricular volume, wall thickness, area change fraction, ejection fraction and tricuspid anulus dimension were measured. All patients with a normalized right ventricular enddiastolic volume of less than 5 ml/m2 and a normalized tricuspid anulus dimension of less than 1.0 cm/m2/3 required a shunt operation. Only one patient with a volume of more than 6 ml/m2 and a normalized tricuspid anulus dimension of more than 1.4 cm/m2/3 required more than relief of right ventricular outflow tract obstruction. In this patient, residual severe pulmonary stenosis necessitated the shunt procedure. One patient with a volume of more than 6 ml/m2 had an anulus diameter of less than 1.4 cm/m2/3 and one patient with an anulus diameter of more than 1.4 cm/m2/3 had a volume of less than 6 ml/m2; both required shunt procedures. It therefore appears that if either the ventricular volume or tricuspid anulus size is excessively small, a shunt procedure is necessary. Wall thickness, area change fraction and ejection fraction measurements were not significantly correlated with right ventricular volume or postoperative outcome.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4019926 TI - Histologic studies on normal and persistent ductus arteriosus in the dog. AB - The process of anatomic closure of the ductus arteriosus was studied at the ultrastructural level in 15 normal beagles (age 0 hour to 13 days) and in 18 specimens from a strain of dogs with hereditary persistent ductus arteriosus (age 4 hours to 27 days). Normal ductal closure takes place from the pulmonary artery to the aortic end. It is accompanied by a series of histologic changes: 1) separation of the endothelial cells from the internal elastic lamina resulting in a wide region of subendothelial edema; 2) ingrowth and infolding of endothelial cells and migration of undifferentiated smooth muscle cells from the inner media into the subendothelial region; 3) apposition of endothelial cells bordering the lumen; and 4) degenerative changes. In persistent ductus arteriosus, these changes do not occur. The endothelial cells remain closely adhered to the internal elastic lamina and the underlying media is abnormal in structure. In the case of partial persistent ductus arteriosus (ductus diverticulum), both the normal and the abnormal type of wall are found in a single ductus arteriosus. The histologic features of the normal and the persistent ductus arteriosus in the dog resemble those of the normal and the persistent ductus arteriosus in humans, suggesting a similar pathogenesis. PMID- 4019927 TI - Treatment of atrial automatic tachycardia by ablation procedures. AB - Sixteen cases of atrial focus tachycardia are described clinically, electrophysiologically and hemodynamically. In each case multiple attempts at drug treatment (average 2.5 drugs) had failed. After delineation of the electrophysiologic mechanism, the patients were treated by surgical removal or cryoablation or catheter electroablation of the focus. In two of four patients catheter ablation was successful and without complication. Surgical treatment was successful in 13 of 14 patients. Left ventricular function, which had been abnormal in 10 patients, normalized in all but 1 patient whose echocardiographic shortening fraction improved from 10 to 27%. There have been no recurrences in a follow-up period of 6 months to 5 years (mean 2.2 years). It is recommended that any atrial automatic focus tachycardia that produces hemodynamic compromise undergo definitive treatment. Patients with chronic tachycardia rates of more than 140 beats/min should be followed up closely. PMID- 4019928 TI - Limitations of failure of procainamide during electrophysiologic testing to predict response to other medical therapy. AB - To determine whether failure of procainamide to prevent initiation of ventricular tachyarrhythmias during electrophysiologic testing predicted failure of other antiarrhythmic regimens, 81 consecutive patients with coronary artery disease whose ventricular tachyarrhythmias remained inducible during procainamide administration were studied. Overall, 26 (12%) of 216 subsequent drug studies were successful and at least one effective drug regimen was identified in 22 (27%) of the 81 patients. Drug success was significantly related to the arrhythmia induced at baseline study; 7% of drug studies were successful in patients with sustained ventricular tachycardia, 24% in patients with ventricular fibrillation, and 29% in patients with nonsustained ventricular tachycardia. An effective drug regimen was found in 11 (19%) of 59 patients with sustained ventricular tachycardia, 4 (50%) of 8 patients with ventricular fibrillation and 7 (50%) of 14 patients with nonsustained ventricular tachycardia. In patients with sustained ventricular tachycardia, failure of procainamide to suppress the arrhythmia correlated with failure of other agents used singly but not in combination. This study supports the view that when procainamide fails to prevent initiation of the arrhythmia in patients with inducible sustained ventricular tachycardia it is unlikely that other individual standard agents will be effective. However, combination regimens may suppress the arrhythmia and should be evaluated. In patients with nonsustained ventricular tachycardia, all agents should be evaluated because failure to respond to procainamide does not predict subsequent responses to other agents either alone or in combination. PMID- 4019929 TI - Diagnostic and therapeutic use of adenosine in patients with supraventricular tachyarrhythmias. AB - Adenosine has been shown to affect both sinus node automaticity and atrioventricular (AV) nodal conduction. The effects of increasing doses of intravenous adenosine were assessed in 46 patients with supraventricular tachyarrhythmias. Adenosine reliably terminated episodes of supraventricular tachycardia in all 16 patients with AV reciprocating tachycardia, in 13 of 13 patients with AV nodal reentrant tachycardia and in 1 of 2 patients with junctional tachycardia with long RP intervals. Adenosine produced transient high grade AV block without any effect on atrial activity in six patients with intraatrial reentrant tachycardia, four patients with atrial flutter, three patients with atrial fibrillation and in single patients with either sinus node reentry or an automatic atrial tachycardia. The dose of adenosine required to terminate episodes of supraventricular tachycardia was variable (range 2 to 23 mg). Side effects were minor and of short duration. These results demonstrate that adenosine is useful for the acute therapy of supraventricular tachycardia whenever reentry through the AV node is involved. When arrhythmia termination is not affected, atrial activity may be more readily analyzed during adenosine induced transient AV block. PMID- 4019930 TI - Milrinone in congestive heart failure: acute and chronic hemodynamic and clinical evaluation. AB - Acute and chronic hemodynamic and clinical responses to milrinone, a new oral inotrope-vasodilator agent, were evaluated prospectively in 37 patients with severe congestive heart failure. The majority of patients (n = 31) had not responded to prior vasodilator therapy, with a substantial number (n = 8) requiring intravenous inotropic support at the time of initial study. All patients showed acute hemodynamic improvement with oral milrinone, and an optimal maintenance dose was chosen for each patient during dose-ranging studies (average dose 48 mg/day). Milrinone was discontinued before follow-up hemodynamic study in 12 patients (because of worsening congestive heart failure in 6 patients, sudden death in 3 patients, arrhythmia in 1 patient and refusal by 2 patients). Hemodynamic effects of milrinone both acutely and after chronic therapy (average 37 days) were compared in the remaining 25 patients. Acutely, mean cardiac index increased from 1.9 +/- 0.5 to 2.5 +/- 0.5 liters/min per m2 (p less than 0.001), and mean pulmonary capillary wedge pressure decreased from 28 +/- 9 to 18 +/- 8 mm Hg (p less than 0.001). When oral milrinone was readministered after chronic therapy, mean cardiac index increased from 1.9 +/- 0.5 to 2.5 +/- 1.7 liters/min per m2 (p less than 0.001), and pulmonary capillary wedge pressure decreased from 27 +/- 8 to 20 +/- 8 mm Hg (p less than 0.001) at 1 hour. New York Heart Association functional class improved in 18 of the 25 patients treated over a long-term period (mean 5.5 +/- 2.3 months).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4019931 TI - Echocardiographic manifestations of tense pericardial effusion. AB - Echocardiography has emerged as a sensitive study in the evaluation of pericardial effusion. The specificity of echocardiographic signs in cardiac tamponade remains undefined, however. Two such signs, early diastolic collapse of the right ventricular free wall and late diastolic collapse of the right atrial wall, were observed in two patients without clinical evidence of cardiac tamponade. Increased intrapericardial pressure was documented in each patient. Accumulation of pericardial fluid under high pressure results in a reversal of the instantaneous transmural pressure gradients in early and late diastole, causing collapse of the right ventricular and the right atrial wall, respectively; however, such a tense pericardial effusion may not cause hemodynamic embarrassment severe enough to yield clinical signs of cardiac tamponade. PMID- 4019932 TI - M-mode echocardiography in constrictive pericarditis. AB - M-mode echocardiograms from 40 patients with proven constrictive pericarditis and 40 subjects without evidence of cardiac disease were reviewed for features previously described in constrictive pericarditis. In this large series, no single feature of the M-mode echocardiogram could be considered diagnostic, although a pattern of normal left ventricular size and systolic function, mild left atrial dilation, flattened diastolic left ventricular posterior wall motion and abnormal septal motion was found in most patients. It is concluded that the M mode echocardiogram can provide findings suggestive of constrictive pericarditis but must be used in conjunction with hemodynamic and other studies to establish the diagnosis. PMID- 4019933 TI - Out-of-hospital automatic cardioversion of ventricular tachycardia. AB - A 42 year old man who survived sudden cardiac death was treated with an automatic implantable cardioverter/defibrillator. After a 5 month symptom-free interval, the patient received two internal discharges in the conscious state while wearing an ambulatory electrocardiographic recorder. Analysis of the tape revealed that both discharges were activated by two bursts of polymorphous ventricular tachycardia, the first one occurring at the end and the second at the onset of episodes of slow, hemodynamically stable monomorphous ventricular tachycardia. This case illustrates the reliability of the automatic implantable cardioverter/defibrillator as an antiventricular tachycardia device and the problem posed by its exposure to nonsustained ventricular tachycardia. PMID- 4019934 TI - Doppler detection of ventricular septal defect. PMID- 4019935 TI - Diltiazem and hyperglycemia-coma. PMID- 4019936 TI - Nutrition in cardiovascular disease. PMID- 4019937 TI - Enhanced incidence of isoproterenol-induced ventricular fibrillation in the magnesium-deficient rat. AB - The electrocardiogram was recorded and serum and bulk myocardial electrolytes were determined in male Sprague Dawley rats, subjected to dietary magnesium deficiency for various periods, to assess the time course of development and cessation of the enhanced arrhythmogenic action of isoproterenol (150 micrograms/kg, subcutaneously) and to establish possible relationships between electrolyte changes and severe ventricular dysrhythmias. Ventricular fibrillation occurred within 60 min following isoproterenol injection in 25, 25, 62.5, 50, and 62.5% of rats on magnesium deficient diet for 4, 7, 11, 15, and 19 days (N = 8), respectively, and resulted in death in most animals (83%). Reintroduction of normal chow following a 30-day period on magnesium-deficient diet normalized serum magnesium (from 1.42 +/- 0.23 to 1.90 +/- 0.08 mEq/liter, mean +/- SD) but did not significantly reduce the incidence of ventricular fibrillation. Magnesium deficiency did not produce statistically significant alterations in bulk myocardial content of sodium, potassium, magnesium, and calcium. However, sodium was elevated and potassium diminished in hearts from rats that died in ventricular fibrillation, but not in those that had recovered. Magnesium deficient rats sacrificed 30 min after isoproterenol injection, that is before the occurrence of ventricular fibrillation, exhibited hypomagnesemia and hypokalemia as well as elevated sodium and diminished potassium and magnesium in the myocardium. In contrast, rats on Purina Chow exhibited hypermagnesemia, but also showed hypokalemia and diminished cardiac potassium. The results indicate that magnesium deficiency enhances the arrhythmogenic propensity of isoproterenol and that the development of ventricular fibrillation is preceded by serum and myocardial electrolyte alterations. PMID- 4019938 TI - Observations on serum and red blood cell magnesium changes in treadmill exercise induced cardiac ischemia. AB - To evaluate changes in magnesium levels with treadmill exercise-induced coronary insufficiency, 59 consecutive patients were studied. In addition to electrocardiographic monitoring, hematocrit, total protein, whole blood, serum and red blood cell magnesium determinations were made before and after exercise testing. Fifteen patients had positive exercise test, 18 did not complete, and 26 had negative exercise test. There was no significant difference in the serum and red blood cell magnesium on the basis of stress test results for ischemia. Although whole blood magnesium, hematocrit, and total proteins increased (P less than .05) in both groups, we did not find a significant change in magnesium homeostasis. PMID- 4019939 TI - Blood and urinary magnesium, zinc, calcium, free fatty acids, and catecholamines in type A and type B subjects. AB - Twenty type A male students were compared to nineteen type B male students (all in apparently good health), before and after exposure to combined stress (noise and task). Before stress, red blood cell (RBC) Zn concentration is higher (P less than .05) and Zn excretion lower (P less than .05) in type A than in type B people. After stress, type A subjects exhibit changes that are larger and more significant than those of type B individuals. After stress, the type A group shows an important increase of urinary catecholamines (P = 2.10(-5), serum free fatty acids, and urinary Zn (P = .001); a slight increase in plasma magnesium (P less than .05); and a small but significant decrease in RBC Mg (P less than .02). These results suggest that type A subjects are more sensitive to stress than are type B people and more readily lose their intracellular Mg, the rise in plasma Mg being a transient one, probably consecutive to the cellular loss. The present observations are in good agreement with published data: ie, the psychological characteristics of type A personalities; their greater susceptibility to ischemic heart disease, which has been associated with Mg deficiency; the possible role of hypomagnesemia in the pathogenesis of hypertension and coronary vasospasm; and the high RBC Zn levels found in hypertensive patients. PMID- 4019940 TI - Interrelationship of dietary Mg intake and electrolyte homeostasis in hamsters: I. Severe Mg deficiency, electrolyte homeostasis, and myocardial necrosis. AB - Epidemiological studies indicate a strong relationship between dietary Mg intake and the incidence of sudden cardiac death. The mechanism by which dietary Mg leads to an increased incidence of cardiovascular disease is unknown but may involve alteration of electrolyte balance. In the present study, tissue electrolyte levels and myocardial pathology were investigated in adult hamsters fed a diet containing no added Mg. Control animals were fed the same diet supplemented with Mg or standard laboratory chow. Hamsters were killed after 4, 8, 12, or 18 days on the test diet, and levels of Na, K, Ca, and Mg were measured in the serum, myocardium, bone, and kidney. The earliest change induced by the test diet was a decrease of the serum Mg and an increase in the Na concentration of the myocardium and other tissues. Following the rise in myocardial Na, the myocardial Ca rose, attaining a fourfold increase by 18 days. K fell in heart and kidney, but not significantly. Although there was no significant change in myocardial Mg, foci of myocardial necrosis, considered to be typical of acute severe Mg deficiency, were found. Myocardial necrosis and the increase in myocardial Ca occurred in parallel. Because of the pattern of observed changes in electrolyte levels, and the potential role of Ca in myocardial injury, the occurrence of myocardial necrosis in these Mg-deficient hamsters is attributable to the increased level of myocardial Ca, rather than to any change in intracellular Mg levels. It is postulated that reduced extracellular Mg levels increase [Na]i through reduction of sarcolemmal (Na+ + K+)-ATPase activity. This would lead to an increase in [Ca]i through Na-Ca exchange. PMID- 4019941 TI - Physiologic changes during a marathon, with special reference to magnesium. AB - In a single case study of a moderately trained, healthy man, physiologic changes during a marathon are reported. Blood was drawn prior to the race, at 1 hour and 2 hours into the race, at the end of the race, and after 1 hour of recovery. By 1 hour into the race, norepinephrine, epinephrine, and dopamine had increased nearly nine-fold, two-fold and five-fold, respectively. After 1 hour of recovery, epinephrine had returned to the pre-race value but norepinephrine and dopamine were still elevated. Cortisol increased gradually and was more than doubled by the end of the race. It was still elevated after 1 hour of recovery. White blood cells gradually increased, reaching their maximum value at the end of the race; a four-to-five-fold increase. Thromboxane B2, which had an inverse relationship to serum magnesium, was below the pre-race value for the first 2 hours but increased nine-fold by the end of the race. Serum magnesium increased from 1.44 meq/l to 1.68 meq/l at 2 hours into the marathon, dropped to 1.07 meq/l by the end of the race, and returned to its pre-race value by 1 hour of recovery. The decrease in serum magnesium at the end of the race may be associated with increased plasma free fatty acid levels. PMID- 4019942 TI - Magnesium and calcium dietary intakes of the U.S. population. AB - Dietary intake levels of calcium and magnesium, as well as calcium/magnesium ratios, were assessed for 12 age/sex groups of the U.S. population through use of USDA's 1977-78 Nationwide Food Consumption Survey. Results indicated that a majority of the U.S. population consumed less than recommended amounts (NRC-RDA) of both calcium and magnesium. Approximately 60% of 0 to 5 year olds and 40% of 6 to 11 year olds had average daily calcium intakes of less than 800 mg, while 60 and 85% of the male and female adolescents, respectively, had intakes below the recommended level of 1,200 mg/day. Approximately 80 to 85% of the adult female groups and 50 to 65% of the adult male groups had average intakes below recommended levels. With the exception of children ages 0 to 5 years, the average daily magnesium intakes of all age/sex classes were below the NRC-RDA. Magnesium consumption was particularly low among adolescent females, adult females, and elderly men, with 85, 80-85 and 75%, respectively, of the population groups having average magnesium intakes below their respective NRC-RDA. Furthermore, the majority of the population groups did not consume appropriate proportions of these two minerals to obtain optimal calcium/magnesium ratios. While adolescent females and adult females had more appropriate ratio values than other segments of the population, these ratios principally resulted from their very low intakes of calcium. The most inappropriate calcium/magnesium ratios, observed for children, male adolescents, and young adult males, were, in general, due to their more appropriate calcium intakes and their low magnesium intakes. PMID- 4019943 TI - Cholesterol, saturated fatty acids, polyunsaturated fatty acids, sodium, and potassium intakes of the United States population. AB - The USDA's 1977-1978 Nationwide Food Consumption Survey was utilized to assess dietary intake levels of cholesterol, fatty acids, sodium, and potassium by several age/sex groups of the U.S. population. Results indicated that mean cholesterol intakes for all male age groups of 12 yr and older exceeded 300 mg/day while the mean intakes of females and children were less than 300 mg/day. However, approximately 30% of each age group of adult females exceeded 300 mg cholesterol per day and only about one-third of the adult males had average intakes of less than 300 mg/day. Between 39% and 44% of total kilocalories were obtained from fat consumption with saturated fatty acids contributing 13-15%, polyunsaturated fatty acids contributing 5-6% and oleic acid contributing 12-14% of total kilocaloric intake. We found that 90% of children ages 6-11 yr and adult females had saturated fatty acids intakes of less than 40 gm/day; 90% of all men had intakes of less than 55 gm/day. At least 90% of all age/sex groups averaged intakes of polyunsaturated fatty acids of less than 26 gm/day. Average daily sodium intakes for each age/sex group (excluding table salt) were within the limits considered safe and adequate. However, approximately 4% of each age group of adult females and about 25% of each of the three younger adult male groups had average sodium intakes of 4000 mg/day or more. Average daily potassium intakes were somewhat low, ranging from 1584 mg/day for children ages 0-5 yr to 2735 mg/day for males ages 51-64 yr. PMID- 4019945 TI - Can allergy meet the challenge of change? PMID- 4019944 TI - Effects on the serum lipoprotein concentrations by lipid-lowering diets with different fatty acid compositions. AB - It has been reported that lipid-lowering diets may reduce high density lipoprotein as well as low density lipoprotein cholesterol but that the reduction of the high density lipoproteins is less pronounced with diets of lower P/S ratios. The aim of the present study was therefore to investigate whether the effects on the low density lipoproteins could be maintained, but those on the high density lipoproteins diminished, by reducing the P/S ratio from 1.3 to 0.7. Fourteen hyperlipoproteinaemic patients in a metabolic ward were given two fat modified diets during two consecutive 3-week periods in a randomized order. The diets were identical with regard to nutrient composition but differed with regard to the P/S ratios, which were 1.3 and 0.7, respectively. The average serum lipoprotein lipid composition and the apolipoprotein concentrations were similar at the end of the two periods. However, in the group of patients (n = 7) who started on the diet with P/S ratio 1.3 the low density lipoprotein cholesterol increased significantly (p less than 0.05) by 7% and the apolipoprotein B concentration by 10% (p less than 0.001) when shifting to the diet with P/S ratio 0.7. No changes of the high density lipoprotein concentrations were seen. The relative content of saturated fatty acids, of oleic acid, and of arachidonic acid in the plasma lipid esters decreased, but the content of linoleic acid increased, when shifting from the diet with a P/S ratio of 0.7 to that of 1.3.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4019946 TI - Eustachian tube obstruction and allergy: a role in otitis media with effusion? PMID- 4019947 TI - National Institutes of Health workshop summary. Summary and recommendations of a workshop on the investigative use of fiberoptic bronchoscopy and bronchoalveolar lavage in individuals with asthma. AB - The participants in the workshop reached unanimous consensus that, as an investigative tool, BAL has enormous potential for extending knowledge of the immunopathogenesis of asthma. When BAL is used according to these guidelines, maximum knowledge may be gained with minimal risks to study subjects. However, we wish to emphasize that the extent to which the safety of the procedure applies to those subjects with asthma and more symptoms and an FEV1 of less than 60% of predicted value remains to be established by carefully controlled clinical investigations. PMID- 4019948 TI - Induction of eustachian tube dysfunction with histamine nasal provocation. AB - This study assessed changes in nasal airway resistance and nasal airway power as well as eustachian tube function after histamine nasal provocation in 12 atopic subjects and 10 nonatopic subjects. Results demonstrated that subjects could not be placed in the atopic or nonatopic group on the basis of prechallenge nasal resistance and power measurements. Atopic subjects demonstrated a statistically significant difference in nasal airway power after histamine provocation (p less than 0.05). Nine of 12 atopic subjects demonstrated tympanometric changes indicative of eustachian tube dysfunction, whereas none of 10 nonatopic subjects had these changes (p less than 0.001). These results suggest a differential sensitivity of nonatopic and atopic individuals to histamine, which may be an important pathogenetic mechanism leading to the development of eustachian tube dysfunction and possible subsequent development of otitis media with effusion in the atopic group. PMID- 4019949 TI - Acute effects of aerosolized metaproterenol on breathing pattern of patients with symptomatic bronchial asthma. AB - We studied the effect of two sequential puffs of metaproterenol (650 micrograms each puff) delivered with an auxiliary aerosol delivery system on the breathing pattern of patients with symptomatic bronchial asthma who were monitored noninvasively with respiratory inductive plethysmography. Particular attention was directed to respiratory center drive as reflected by mean inspiratory flow and minute ventilation. Both these components were elevated in the eight patients whose mean FEV1.0 was 1.43 L (45% predicted normal). Two puffs of metaproterenol produced a maximal increase over baseline in FEV1.0 of 50 +/- 25% (SD), whereas no change took place in FEV1.0 with placebo administration. This dose of metaproterenol did not alter heart rate nor blood pressure throughout the study period of 2 hours. Neither mean inspiratory flow, minute ventilation, nor any component of the breathing pattern changed with this partial reversal of bronchoconstriction. These results suggest that the neural mechanism accounting for heightened respiratory center drive in patients with symptomatic bronchial asthma does not wholly depend on bronchoconstriction. PMID- 4019950 TI - Prolonged bronchial obstruction after a single antigen challenge in ragweed asthma. AB - Some patients with allergic asthma exhibit late-phase responses to inhalation challenge with specific antigen. However, the duration of these responses is difficult to determine because of diurnal variations in airway function, a common phenomenon in patients with asthma. We therefore examined the pattern and duration of pulmonary function in six asymptomatic patients with a history of ragweed asthma and a documented late-phase response after specific and nonspecific bronchial challenge and compared them to responses after control challenge with normal saline. On 3 different days, specific airway conductance (SGaw) and gas distribution by the single breath nitrogen test were measured before (9:00 A.M.) and hourly for 24 hours after inhalation challenge with either normal saline, ragweed extract, or histamine at concentrations sufficient to decrease SGaw immediately by 35% or more. The fluctuations in SGaw after saline and histamine were considerable but failed to follow a typical diurnal or biphasic pattern. There was no difference in mean SGaw between the histamine and saline challenges from 1 to 24 hours after inhalation. In contrast, ragweed challenge produced a typical late-phase response followed by partial recovery of mean SGaw. However, mean SGaw remained subsequently lower than after saline challenge throughout the remaining observation period with fluctuations about this lower level. Gas distribution demonstrated marked intra- and intersubject variations and was therefore not different among the three challenges at any time of measurement. These observations suggest that a single specific but not nonspecific bronchial challenge causes prolonged airflow obstruction in subjects with allergic asthma that lasts 24 hours or longer, independent of variations in baseline airway function. PMID- 4019951 TI - Allergenicity, immunogenicity, and safety of immunotherapy with various molecular weight ranges of polymerized ragweed. AB - Since the observation had been made that allergenicity of polymerized ragweed (PRW) varies inversely with molecular weight over ranges we had studied previously, we conducted this study to determine the utility of immunotherapy with PRW molecular weight greater than 20,000,000 alone or as part of a final product pool. Twenty-one patients with ragweed pollinosis were randomized into three groups on the basis of ragweed skin test titration. Each patient received 500 micrograms AgE (50,000 PNU) of one of the following molecular-weight ranges: PRW A greater than 500,000; PRW B 200,000 to 20,000,000; and PRW C greater than 20,000,000. There was no difference between PRW A, B, and C by intradermal end point titration, by incidence of large local reactions, by amount of erythema or induration from injections, or by rise in blocking antibody that was significant in each group. There were no systemic reactions nor any changes in clinical laboratory parameters. In summary, each of the molecular-weight ranges of PRW studied was similarly allergenic, immunogenic, and safe to administer, and thus PRW greater than 20,000,000 can be used for immunotherapy as a part of the final product pool. This has the advantages of increasing yields and of simplifying the fractionation by eliminating one chromatographic process. PMID- 4019952 TI - Effect of anaphylaxis on conjunctival goblet cells. AB - Rats undergoing ocular anaphylaxis induced by systemic or local injection of antigen, topical application of antigen, or topical application of compound 48/80 were evaluated conjunctival goblet cell changes that might be related to anaphylaxis. The number of goblet cells in 1 micron, alkaline Giemsa-stained sections averaged 500/mm2 of epithelium in normal rats; this number was not significantly changed in any of the experimental groups. Goblet cells in control rats occasionally demonstrated evacuation of their contents (less than 1%) or upward displacement of the intracellular bolus of mucus (about 1%); these percentages were not increased in anaphylaxis. Topical application of 2.0 micrograms of histamine induced an intracellular displacement of mucus in both control animals and animals undergoing anaphylaxis. These findings suggest that in ocular anaphylaxis the amount of histamine released may be insufficient to produce such intracellular changes. Our results indicate that in ocular anaphylaxis in the rat, there is no light microscopic evidence of increased mucus discharge from conjunctival goblet cells. Increased mucus in secretions of patients with ocular allergic syndromes may not be attributable to anaphylactic mechanisms alone. PMID- 4019953 TI - The immediate and short-term effects of corticosteroids on cholinergic hyperreactivity and pulmonary function in subjects with well-controlled asthma. AB - We investigated the immediate effect of corticosteroids on pulmonary function (FEV1 and forced expiratory flow measured between 25% and 75% of vital capacity) and methacholine airway reactivity during a period of 8 hours after an intravenous bolus of 6-methyl-prednisolone (1 mg/kg) or saline placebo administered in a double-blind, crossover schedule in 12 patients with well controlled asthma. The short-term effect of corticosteroids was also studied with bronchial reactivity to methacholine and pulmonary function measured before and at the end of 8 days of 6-methyl-prednisolone therapy (32 mg once a day, orally) in a group of six treated subjects as well as in a control group. There were no immediate or short-term effects from 6-methyl-prednisolone on bronchial response to inhaled methacholine. After 8 days of corticosteroid administration, forced expiratory flow measured between 25% and 75% of vital capacity significantly increased in the treated group (p less than 0.025). We concluded that "primary hyperreactivity" appears to be insensitive to an intravenous bolus or 8 days of treatment with oral corticosteroids and that the improvement in respiratory function is slight and slowly evolving in subjects with well-controlled asthma. PMID- 4019955 TI - Asthma '84: pharmacologic update. October 31 to November 3, 1984, Rancho Mirage, California. PMID- 4019954 TI - Steroid myopathy: incidence and detection in a population with asthma. AB - Sixty steroid-treated patients with asthma were evaluated for the presence of muscle weakness by use of both manual muscle testing and the Cybex II isokinetic dynamometer. The patients were compared to age and sex-matched sedentary control subjects. Forty-eight percent of the patients (12/25) taking greater than or equal to 40 mg per day of prednisone had hip flexor strength greater than or equal to 2 SD below the mean of age and sex-matched control subjects by Cybex testing (CT). Sixty-four percent of the patients (16/25) taking greater than or equal to 40 mg per day of prednisone were found on manual muscle testing to have hip flexor weakness. Only one patient taking less than 30 mg per day of prednisone was found to have muscle weakness. Biochemical parameters, including CPK, aldolase, SGOT, LDH, and LDH isoenzymes were measured to assess the degree of steroid-induced muscle damage. They neither correlated with the degree of hip flexor weakness as measured by CT, nor did they discriminate between patients receiving small doses and large doses of steroids. Changes in urinary excretion of creatine did not help to confirm the diagnosis of steroid myopathy. Although CT provides an objective means of assessing muscle strength in these patients, at this time no definitive chemical test is available for the diagnosis of steroid myopathy. PMID- 4019956 TI - Theophylline product and dosing interval selection for chronic asthma. AB - Unless they are taken at unacceptably frequent intervals, conventional rapid release theophylline tablets and liquids produce excessive serum concentration fluctuations, particularly in patients with rapid elimination. Slow-release formulations provide more stable serum concentrations with longer dosing intervals if absorbed completely, consistently, and at a sufficiently slow rate and thus have the potential to improve efficacy and compliance. However, there are clinically important differences in the extent and rate of absorption among the 15 slow-release formulations available under 29 brand names in the United States. Fluctuations in steady-state serum concentrations are a function of the absorption rate of the product, the elimination rate of the patient, and the dosing interval. In patients with slow elimination, clinically relevant differences among formulations are not apparent with twice-daily dosing. Among patients with more rapid elimination, however, available data for only two products demonstrate sufficiently slow absorption to justify routine twice-daily use without excessive fluctuations. More rapidly absorbed formulations must be administered at 8-hour intervals in such patients to prevent breakthrough in asthmatic symptoms before the next dose, despite promotional claims to the contrary. Current products approved for "once-a-day" dosing are clinically inadequate because of incomplete or erratic absorption or excessive serum concentration fluctuations. Lastly, food intake induces dose dumping of potentially toxic amounts of theophylline from Theo-24 and greatly impairs absorption from Theo-Dur Sprinkle capsules but has no important effect on Theo Dur tablets. The effects of food on most other theophylline products are not known. PMID- 4019957 TI - Clinical pharmacodynamics of theophylline. AB - The clinical pharmacodynamics of theophylline, which concerns the correlation between the serum theophylline concentration ([TH]) attained during therapy for asthma and improved pulmonary function or unwanted side effects, serves to link the pharmacokinetics of theophylline with the time course of clinical outcome. Although the minimum effective and maximum safe [TH]s have been known for some years, it was only recently shown that maximal improvement in pulmonary function lags behind rapidly changing [TH]s and that improved pulmonary function relates to increasing [TH]s within the therapeutic range. While much is known about the determinants of theophylline disposition in patients with asthma, enabling individualized pharmacokinetically based therapy, it is difficult to predict the clinical pharmacodynamic outcome. Investigation of the effects of age, cardiopulmonary disease, concurrent drugs, diet, circadian rhythms, and other patient features on theophylline clinical pharmacodynamics may provide a basis for prediction of individual patient responsiveness to theophylline and lead to further optimization of theophylline therapy in asthma. PMID- 4019958 TI - Theophylline toxicity. AB - The adverse effects of theophylline were recognized soon after its introduction into clinical medicine. Reports of major toxic reactions to theophylline, particularly in children, discouraged its use and led to homeopathic dosing recommendations that had little therapeutic effect. Concomitant with the renaissance in theophylline use during the past decade, reports of theophylline toxicity have increased. The epidemiology of theophylline intoxication has changed in recent years, and today most instances of serious toxicity are due to intentional overdosage, as in a suicide attempt. The adverse effects of theophylline involve the gastrointestinal, nervous, cardiovascular, and urinary systems. In addition, significant metabolic derangements are noted in patients with severe intoxication. Treatment of theophylline intoxication involves attention to fluid and electrolyte balance and initiation of measures to remove theophylline from the body (gastric lavage or emesis, repeated charcoal administration by mouth, and charcoal hemoperfusion in serious cases). PMID- 4019959 TI - Overview of corticosteroid therapy. AB - Corticosteroids have been recognized as useful in the management of asthma for the past 35 years. Controversy remains as to their precise indications, dosage, and optimal methods of administration. Only recently has objective evidence been presented confirming their usefulness in acute severe attacks and status asthmaticus. In the treatment of the latter, high doses of methylprednisolone (125 mg every 6 hours) has been shown to be more effective than lower doses. The corticosteroids are also useful diagnostically to determine reversibility of airway obstruction in the bronchitis-emphysema syndrome. To prevent adrenal insufficiency, they are mandatory for patients previously receiving long-term systemic corticosteroid therapy who are undergoing stress (e.g., surgery). Indications for chronic severe asthma are the least well established. Patients with severe incapacitating asthma uncontrolled by bronchodilators or cromolyn should be considered candidates for corticosteroid therapy. When long-term therapy is necessary, aerosolized corticosteroids or alternate-day therapy are preferable to daily dosing. Regardless of the route used, it is advisable to limit the use of these agents to patients who clearly require them and to take all precautions to minimize side effects. Neither method, especially when higher doses are used, obviates possible development of serious complications. PMID- 4019960 TI - Inhaled corticosteroid therapy: a substitute for theophylline as well as prednisolone? AB - Topical corticosteroid treatment can be successfully achieved by inhaled therapy and can effectively provide a safe substitute for oral steroids. More than 8 million patient years of experience gained over a decade of use of inhaled steroids has shown them to be acceptable to patients and clinicians, with side effects confined to the upper airway. At daily doses of 200 to 1600 micrograms BDP or the equivalent, minor systemic activity may occasionally be demonstrated but no adverse systemic side effects have been reported. The topical anti inflammatory treatment provided by inhaled steroids thus compares favorably with prednisolone and with other asthma therapy with respect to morbidity and mortality, suggesting that inhaled steroids combined with an inhaled beta-agonist is a safe and comprehensive treatment for chronic asthma. This parallel attack on inflammation and bronchoconstriction can be achieved with a morbidity that is much less than that of asthma and also likely to be less than that of the frequently used combination of theophylline and inhaled beta-agonist. Twice-daily regimens of inhaled steroids over a dose range of 200 to 1600 micrograms BDP or the equivalent should enable most patients with chronic asthma to receive effective therapy without recourse to potentially more toxic oral bronchodilator or steroid therapy. PMID- 4019961 TI - Immunologic and therapeutic aspects of ketotifen. AB - Ketotifen, a benzocycloheptathiophene, possesses asthma-prophylactic and antiallergic activities in a number of in vitro and in vivo systems: prevention of cutaneous and lung anaphylaxis in the rat and guinea pig; inhibition of dermal and bronchial antigen challenges in man; inhibition of mediator release from rat mast cells, human basophils, human neutrophils, and human and guinea pig chopped lung; reduction of human neutrophil activation induced by PAF-acether; functional antagonism of mediator effects in the guinea pig; blockade of H1-receptors and prevention and reversal of beta-adrenergic tachyphylaxis in the rat. These properties make ketotifen suitable for the long-term prophylaxis of bronchial asthma and for the prevention and treatment of other allergic disorders, such as allergic rhinitis and conjunctivitis, food allergy, and urticaria. Oral ketotifen (1 mg twice daily) is particularly convenient in the management of the multiple allergies often encountered in patients with atopy. PMID- 4019962 TI - Immunotherapy: parameters of assessment. AB - Allergen immunotherapy has proved safe and effective for selected aeroallergens that can be studied under controlled conditions. Various mechanisms of action have been proposed with limited evidence for their role in the protection resulting from immunotherapy. The exception is blocking antibody, which was discovered 50 years ago. In eight successive studies sponsored or carried out by one institution in which clinical efficacy was demonstrated, the serum level of IgE antibody was unchanged or slightly increased. All eight studies showed a significant rise in the serum level of IgG antibody, and this response is the logical immunologic explanation for clinical efficacy. For aeroallergens that cannot be avoided or subjected to clinical efficacy studies, demonstrations of safety and of significant IgG antibody response constitute the appropriate method of assessment. PMID- 4019963 TI - Child survivors of the holocaust: 40 years later. Introduction. PMID- 4019964 TI - Legal aspects of child persecution during the holocaust. PMID- 4019965 TI - Role of memories in lives of World War II orphans. PMID- 4019966 TI - Therapeutic value of documenting child survivors. PMID- 4019967 TI - Longitudinal follow-up of child survivors of the holocaust. PMID- 4019968 TI - Child survivors of the holocaust--40 years later: reflections and commentary. PMID- 4019969 TI - The development and validation of the children's self-report psychiatric rating scale. PMID- 4019970 TI - Construct validity of clinical diagnosis in pediatric psychiatry: relationship among measures. PMID- 4019971 TI - Informant variance: the issue of parent-child disagreement. PMID- 4019972 TI - Children's attachment to soft objects at bedtime, child rearing, and child development. PMID- 4019973 TI - The relationship of weight gain and caloric intake in infants with organic and nonorganic failure to thrive syndrome. PMID- 4019974 TI - Indochinese immigrant children: problems in psychiatric diagnosis. PMID- 4019975 TI - The stability of cognitive and linguistic parameters in autism: a five-year prospective study. PMID- 4019976 TI - Autistic children as adults: psychiatric, social, and behavioral outcomes. PMID- 4019977 TI - Suicidal behavior by hospitalized preadolescent children on a psychiatric unit. PMID- 4019978 TI - Neurological dysfunction in serious delinquents. PMID- 4019979 TI - Combined use of tricyclic antidepressants and neuroleptics in the management of terminally ill children: a report on three cases. PMID- 4019980 TI - Major depressive disorder in a preschooler. PMID- 4019981 TI - Multiple personality in a 10-year-old girl. PMID- 4019982 TI - Use of the infant temperament questionnaire. PMID- 4019983 TI - Current and future foodservice applications of microwave cooking/reheating. AB - Microwave ovens are widely used in foodservice establishments; currently, they are used primarily for reheating. In comparison with conventional methods, approximately 75% less energy is required for microwave cooking or heating. In the future, it is possible that minimal microwave energy will be used to extend shelf life of foods. It is expected that "combination" convention or convection/microwave systems and conveyor microwave systems that can be electronically programmed will be widely used in the future. New food product designs and types of disposable packaging are available. PMID- 4019984 TI - A comparison of career-entry administrative competencies with skills required in practice: implications for continuing education. AB - Dietitians, advancing in practice, are often required to fill expanding administrative roles without the benefit of additional formal preparation. A study was conducted to compare career-entry administrative competence with competence needed for current practice. The survey instrument contained 59 generic administrative competency statements categorized under the headings of organization and administration; leadership and supervision; personnel management; space, equipment, and materials management; communications; financial management; and quality assurance of services. The questionnaire was sent to the 138 administrative dietitians practicing in Nebraska. Completed questionnaires were returned from 50 dietitians, a 35% response rate. Results of a Student t test analysis indicated a statistically significant difference between the two competency levels for each major category of administrative skills. The data support the need for multiple continuing education opportunities for dietitians to develop skills needed for their expanding managerial responsibilities. PMID- 4019986 TI - Development of an assessment form: attitude toward weight gain during pregnancy. AB - A Likert-format questionnaire with 18 statements expressing attitudes of pregnant women toward their own pregnancy weight gain was developed and tested. Attitudinal data and actual weight gain were obtained from 29 women to determine whether attitudes toward slimness affect weight gain during pregnancy. Forty-one percent of the respondents had a negative attitude toward pregnancy weight gain. Attitude scores related significantly with actual weight gains (p less than .025) but not with age and number of previous pregnancies. Knowledge of appropriate weight gain and recommendation of the doctor also exerted significant influences on weight gains (p less than .05). This study suggests that attitudes favoring slimness may relate to lower maternal weight gains during pregnancy. PMID- 4019985 TI - Food consumption and quality of diets of Kansas elementary students. AB - Better knowledge of the eating patterns of children would allow nutritionists to target nutrition information more effectively. Twenty-four-hour dietary recalls were collected from 1,242 elementary students to investigate their eating patterns. Foods consumed were classified into categories on the basis of similar composition. Dietary quality was assessed by calculating mean adequacy ratios. Grain products, high-protein foods, vegetables, and milk products were included in the diets of almost all students. Sugary products were consumed by almost 90%, 20% drank non-sugary beverages, and fats and oils were included by 80%. Also, 80% consumed fruits and juices. Consumption of milk and milk products was the most important estimator of dietary quality, followed by vegetables, mixed protein dishes, nutrient supplements, fruits, high-protein foods and grain products. When nutrient supplements were excluded, fruit and grain products became more important predictors. Non-sugary beverages adversely affected the quality of children's intakes. Students with dietary quality indexes between 90 and 100 consumed milk and vegetables more frequently than those with indexes of less than 66, who drank non-sugary beverages more often. Dietary quality varied in direct proportion to level of energy intake, suggesting that nutrition education should emphasize intake of nutrient-dense foods. PMID- 4019987 TI - Salicylates in foods. AB - To determine salicylate content, 333 food items were analyzed. Foods were homogenized with 25% sodium hydroxide, allowed to stand overnight, acidified with concentrated hydrochloric acid, and then extracted with warm diethylether over 5 hours. The extract was dried and taken up in dilute sodium bicarbonate solution for analysis. Salicylic acid was separated by high performance liquid chromatography and quantified by reading at 235 nm. Salicylic acid standards were used throughout to standardize extractions and analyses. This is the most comprehensive set of data on food salicylates yet published; extraction appears to have been more complete for some foods, giving higher values than those previously published. Most fruits, especially berry fruits and dried fruits, contain salicylate. Vegetables show a wide range from 0 to 6 mg salicylate per 100 gm food (for gherkins). Some herbs and spices were found to contain very high amounts per 100 gm, e.g., curry powder, paprika, thyme, garam masala, and rosemary. Among beverages, tea provides substantial amounts of salicylate. Licorice and peppermint candies and some honeys contain salicylates. Cereals, meat, fish, and dairy products contain none or negligible amounts. PMID- 4019988 TI - Typology of food preferences identified by Nutri-Food Sort. AB - A Q-sort instrument to measure and identify a typology of food preferences was developed and tested. Sixty-eight pictures of food items were used for the Q-sort called the Nutri-Food Sort. Foods chosen were divided evenly among the following categories: low nutrient/high calorie, low nutrient/low calorie, high nutrient/high calorie, and high nutrient/low calorie. Ninety-seven women sorted the pictures on the basis of preference on a 7-point scale from "like a lot" to "dislike a lot." The results were factor analyzed (Q-type), producing four distinct respondent groups or types. The types were labeled: "finicky eaters," "health-conscious dieters," "diverse diners," and "high-calorie traditionalists." The "finicky eaters" favored only 8 foods and disliked 40. "Health-conscious dieters" preferred low-calorie foods. The "diverse diners" preferred a wide variety of foods and were more adventuresome in their choices. The "high-calorie traditionalists" preferred high-calorie foods and "all-American" favorites. The four food preference categories originally predicted were partially accurate descriptions of the resulting four food preference factor groups. Overall, the Nutri-Food Sort appears to be a versatile instrument that has wide applicability in research on food behaviors, attitudes, and preferences. PMID- 4019990 TI - Nutrition services at a university student health center. PMID- 4019989 TI - Strategies for increasing productivity. AB - In today's arena of competition, cost-containment, quality assurance, and high technology, the dietitian is challenged to develop and implement strategies that will assure an increase in productivity. Within a government system, such strategies must address the political climate as well as administrative and management issues. Prior to modifying any system or part of a system, it is critical to develop evaluation criteria. Each of the eight strategies discussed in this article is effective in promoting an increase in productivity. PMID- 4019991 TI - Fluid retention and weight reduction in perimenopausal women. PMID- 4019992 TI - Medical nutrition education: an assessment of nutrition education in a family practice residency program. PMID- 4019994 TI - Tuberculosis in the elderly. The Grey Plague. PMID- 4019993 TI - Use of traditional Indian foods by Cherokee youths in Cherokee, North Carolina. PMID- 4019995 TI - Acute hospitalization in a home for the aged. AB - All acute hospitalizations from a 229-bed home for the aged for a four-year period were analyzed. Of 373 residents eligible for the study, 239 individuals were hospitalized a total of 503 times. Five patients were admitted seven times. Median length of stay was 9.4 days. Of 235 primary diagnoses, only nine occurred at least 1% of the time. Sixty-six different complications, representing 131 occurrences, were noted during hospitalization. Hospital mortality was 11.7%. Of first admissions 9.2% died and 19% of survivors required a higher level of care. One year later 40% had died and 17% were at a higher level of care. Logistic regression identified four variables significantly associated with death within six months of first hospitalization: age, hospital complication, surgical procedure, and diagnosis of acute myocardial infarction. Compared with nonhospitalized residents, hospitalized residents were more likely to be male, but no age effect was noted. Survival differences did not emerge until the third year of the study. PMID- 4019996 TI - Comparison of hospitalization between nursing home and community residents. AB - The authors prospectively identified 96 consecutive nursing home residents (NHR) admitted to the medical wards of their affiliated hospitals to determine the outcome of hospitalization for these patients in comparison with 88 admissions in a similarly aged community residents (CR) population. Nursing home and community resident groups were similar in age, sex, marital status, and distribution among the four study hospitals. Dementia was a more common preexisting diagnosis in NHR than in CR. Reasons for admission differed between the two groups. Although NHR experienced a longer hospitalization than CR, frequency and duration of intensive care unit admissions were similar. Fatal outcome occurred more commonly in NHR compared with CR (27 v 11%, P less than .001). Predictors of mortality were examined. Nursing home residents also experienced a higher mortality than CR within the six months after hospitalization (35 v 20%, P less than .005). PMID- 4019997 TI - Prevalence and significance of cardiovascular disease and hypertension in elderly patients with dementia and depression. AB - The prevalence and significance of clinical heart disease and hypertension were compared in three groups of elderly patients. One group was diagnosed as dementia of an Alzheimer's type (AD), another as multiinfarct dementia (MID), and the third as major depression. Clinical heart disease and hypertension were uncommon in the AD group with the prevalence being lower than that reported in most epidemiologic studies. Four percent of the AD patients had a history of myocardial infarction, 5% angina, 1% arrhythmias, and 3% heart failure. Electrocardiographic changes of an old myocardial infarction were present in 9%, atrial fibrillation in 1%, and left ventricular hypertrophy in 3%. A history of hypertension was present in 24% of the AD patients. In comparison, a history of myocardial infarction, angina, and heart failure was five times greater, and electrocardiographic abnormalities were twice as prevalent in the MID group. A history of hypertension was three times more common and actual blood pressure readings were higher. In the depression group heart disease was not uncommon and the prevalence, in general, was comparable with the MID group. However, a history of increased blood pressure and actual increased blood pressure readings were statistically less than in the MID group. PMID- 4019998 TI - Thyroid disease in patients with dementia of the Alzheimer type. AB - The authors compared the frequencies of prior thyroid disease, thyroid medication use, and abnormal serum thyroxine levels in 61 patients with dementia of the Alzheimer type (DAT) with those of 38 control subjects. They found that the 33 women with DAT had a 24.2% frequency of prior thyroid disease, comparable with that found in a previous epidemiologic study. The 19 female controls, however, had a similar frequency, failing to support a previously reported association between DAT and thyroid disease. PMID- 4019999 TI - Incidence and correlates of incontinence in stroke patients. AB - The incidence of incontinence in a series of 135 consecutive stroke patients was 51% (urine) and 23% (feces) within one year. In 75% the urinary incontinence started within the first two weeks, and in 41% it had cleared during that time. Incontinence at onset is associated with measures of severity of stroke (and of immobility for fecal incontinence). Among 92 survivors at one year, 15% were incontinent of urine, a proportion that rose in two- and three-year survivors to 23 to 24%, but by four years was again 14%, a level similar to that of the general elderly population. It is concluded that incontinence is more commonly a by-product of immobility and dependency than of involvement of the neurologic pathways, and most of it is transient. PMID- 4020000 TI - Hallucinations of widowhood. AB - Widowed residents of two nursing homes who were oriented to person, time, and place were interviewed to determine the extent to which they had hallucinatory experiences of their deceased spouse. Fifty-two interviews were completed with 46 widows and six widowers. Results are reported for the widows. Twenty-eight (61%) of the widows reported hallucinatory experiences of their deceased spouse. Twenty four (86%) of the widows described the experiences as good or helpful. Thirteen (46%) reported that the experiences continue to happen. Nineteen (54%) of the widows had never discussed the experiences with anyone before this study. These results are surprisingly similar to previously published findings by Rees in Wales and suggest that these experiences are more common in the United States than has been recognized. PMID- 4020002 TI - Need for medical workup in psychiatric assessment. PMID- 4020001 TI - Tuberculosis in a geriatric unit. AB - All cases of tuberculosis admitted to a geriatric unit over five years were reviewed. The problems involved in diagnosing and managing the disease in the elderly are discussed, emphasizing the importance of diagnosing a treatable disease that may otherwise be fatal. PMID- 4020003 TI - Assessing depression in evaluating memory impairment. PMID- 4020004 TI - Challenge on visual stress. PMID- 4020005 TI - Is your office computerized? PMID- 4020006 TI - The IVEX refraction system: a clinical comparison. AB - A new refraction system employing traditional modes of testing combined with microprocessor-based electronics and new optical technology was evaluated in a controlled study to determine if the instrument produced subjective refractions corresponding to the traditional refractor. Subjects ranged in age from 14 to 25 years and the study excluded any individual exhibiting ocular or systemic diseases and binocular problems. In addition, tests were made to determine if "instrument myopia" was present. The results showed that data from the IVEX Refraction System correlated highly with data from the standard refractor, but a small amount (0.25 D to 0.37 D) of instrument myopia was present in most instances. PMID- 4020007 TI - Minimizing risk of adverse reactions to mydriatic agents in binocular indirect ophthalmoscopy. AB - To minimize the risk of adverse side effects from mydriatics during binocular indirect ophthalmoscopy, a procedure was developed which intentionally starts with a dose significantly less than an ED99. Using a clinically effective diameter of greater than 7 mm as a criterion, I found that 1 drop of 0.5% tropicamide (T) constituted an ED74 (N = 46). When 1 drop of 2.5% phenylephrine (P) was added, this increased to an ED93 (N = 27). If present results can be generalized, then 1 drop of T, supplemented at 30 minutes with 1 drop of P, if necessary, should produce satisfactory dilatation in approximately 90% of the subjects. PMID- 4020008 TI - Visual skills and intellectual development: a relationship in young children. AB - The development of convergence, ocular motilities; stereopsis and form perception for infants and young children was evaluated in a previous paper. This study examines the relationship between these visual skills and intellectual development. Young children (n = 130) were assessed longitudinally every six months from the ages of 12- to 42-months. The results showed positive and significant correlations between visual skills and intellectual development during infancy and the preschool years. Stereopsis and form perception correlated most highly and consistently with intellectual development. PMID- 4020009 TI - The prevalence of corneal arcus senilis in known insulin-dependent diabetic patients. AB - Corneal arcus senilis has long implied cardiovascular disease because of its association with altered lipid levels. This study demonstrates that arcus senilis does not have a higher prevalence rate in diabetics than non-diabetics in spite of the increased cardiovascular risk in insulin-dependent diabetics. PMID- 4020010 TI - General binocular dysfunctions in an urban optometry clinic. AB - The prevalence of general binocular dysfunction with asthenopia was determined for non-presbyopes at an urban optometry clinic serving municipal workers and their dependents. Of the sample of 119 patients, 42.9% had jobs with heavy desk work demands (primarily secretarial and clerical) and 39.5% were students. The prevalence of symptomatic general binocular dysfunction was 21.0%. Accommodative dysfunctions were the most commonly encountered condition at 16.8%. Symptomatic near esophoria was found in 5.9% of patients and convergence insufficiency in 4.2%. Both vergence dysfunctions overlapped with accommodative dysfunctions. PMID- 4020011 TI - A case in point extended. AB - No visual examination can be considered complete without visual field investigation. Garmizo suggests at least a hand confrontation, and Goodlaw urges a refinement of this procedure using a wand with a 3" by 3" background to a 3mm target. There is also a question of body clues to hand location when the hand is the target. This suggested procedure circumvents this by using a 6" to 8" long handle on the target. PMID- 4020012 TI - Pros and cons of a Fresnel lens low vision aid. PMID- 4020014 TI - Computer systems should do more than blink at you. PMID- 4020013 TI - Office design uses Arizona sun. PMID- 4020015 TI - Psychoanalysis of the older patient. AB - A small informal poll of local colleagues revealed that despite their interest in the subject, many had doubts about the possibility of analyzing persons aged sixty or over successfully. Their specific questions are collated and are offered as a sample of the questions in the minds of many analysts everywhere. Selected material from the ongoing analysis of a sixty-four-year-old patient is presented that bears on some of the questions raised. In addition, changes in the patient are noted. These are discussed in terms of changes in function, which are equated with structural change. The major thrust of the paper is that development continues throughout the life course, and that the criteria for analyzability remain constant. The chronological age of the adult by itself is not an indicator of eligibility or of suitability for psychoanalysis. PMID- 4020016 TI - Psychoanalysis as science: the inductivist's resistance revisited. AB - The scientific status of psychoanalysis has been the focus of heated debates among philosophers of science and among psychoanalysts. The most recent challenge to psychoanalysis as a science comes from the quarters of the inductivist philosophy of science. Since inductivism is a self-defeating philosophy, it is not surprising that inductivists demand that psychoanalysts pay an unlimited price for their claim of scientific status for psychoanalysis. Most psychoanalysts, in their response to this impossible challenge, unwittingly claim to have paid the price. What is worse, the claim is made in a confused and emotionally charged manner. Hence, psychoanalysts are usually defensive and, thus, in error when repelling (in this way) the attack of the inductivist philosopher. It is not psychoanalysis inductivists attack, but their own commitment to their own logic which leads inexorably to the dissolution of their argument, of all science, and, indeed, of psychoanalysis as well. It seems much more reasonable to postpone any response to the challenges that confront psychoanalysis today and to invest effort in a reformulation of the problem of the scientific status of psychoanalysis. Different rational solutions to the problem may evolve if we take care to become well informed first about the limits of our theoretical frameworks and show readiness to change them, if and when needed. That is to say, we can start with a somewhat tentative, not to say skeptical, frame of mind concerning the very concept of scientific status. We may try to keep and to contain our skepticism to the degree required by the discourse at hand, carry on exploring in our practice, report our results, and discuss them respectfully. We should start by admitting that, quite possibly, our discourse will end inconclusively. PMID- 4020017 TI - A reexamination of the concept "object" in psychoanalysis. Panel report. PMID- 4020018 TI - Reanalysis. Panel report. PMID- 4020019 TI - The Oedipus complex: a reevaluation. Panel report. PMID- 4020020 TI - Perspectives on the superego. Panel report. PMID- 4020021 TI - Irony in psychoanalysis. AB - Irony is a more important element of analysis than we generally recognize. First, verbal irony characterizes the discourse of certain patients who employ it as a defense, both adaptively and as a resistance, especially against the expression of intense affect associated with the transference. The frequent employment of irony reflects a significant character trait, an habitual mode of dealing with conflict. It is also a frequent manifestation of a particularly active self critical faculty. Ironic employment of a "double audience" is also relevant to analytic technique. Second, situational irony is inherent in many aspects of psychoanalysis, as a process and a point of view. It implies the acceptance of the inevitability of conflict, ambiguity and paradox, never quite capable of perfect resolution. It emphasizes critical examination of mixtures of motives of both analysand and analyst, and it requires perpetual questioning of what might otherwise be taken as accepted doctrine, including the principles of psychoanalysis per se. An ironic stance requires some degree of detachment in conjunction with deep commitment, itself an ironic circumstance. Third, the capacity to understand and employ irony can be traced to childhood, relatively early in the course of development of speech and sphincter control; some of its early determinants are to be found in the anal phase of psychosexual development; it reflects as well the capacity to use certain early defenses and mechanisms originally described as characteristic of the dream work. Its later fate as a prominent feature of character is very much a matter of ego and superego development, including such components as intelligence, verbal skills, the capacity for joking and for play, i.e., controlled regression. Sources of identification in the family and the culture are of obvious importance. Finally, an understanding of irony has an important place in the theory of technique, especially with regard to transference and resistance. An ironic stance and understanding on the part of the analyst are valuable, even essential; but irony may become a questionable defense for him as well as for his patient. PMID- 4020022 TI - Psychoanalysis, philosophy, and the public. PMID- 4020023 TI - On the theory of theory in psychoanalysis and the relation of theory to psychoanalytic therapy. PMID- 4020024 TI - The development of the drive object concept in Freud's work: 1905-1915. AB - In 1905 Freud established the idea of an object of an instinctual drive as the basic object concept of psychoanalysis. He also introduced the derivative concepts of object directedness, object choice, and object finding. While taking these steps he simultaneously deemphasized the importance of drive objects in sexual life, contradicted himself on whether drives are autoerotic or object directed in infancy, and made incompatible statements about whether or not object choice occurs before puberty. Freud's clinical work, reflected especially in the major case reports and a series of papers on fantasy, led to an apparent recognition of complexity in the mental life of children far greater than had been described earlier. The increased attention to and appreciation of mental content in childhood especially augmented Freud's understanding of the role of drive objects, object directedness, and object choice in infancy. This, in turn, led him to postulate a sequence of organizations of sexual life, named according to the zonal drive source plus the mode of object directedness, a process of theory development that continued through 1924. Object choice and, to a lesser extent, object directedness are concepts derived from and dependent upon the concept of drive object. Both require, however, explanatory constructs besides drive constructs. In 1915 Freud defined the term "object" in the context of stating his drive theory. Freud used the term object with several new modifying words during this decade. No new object concept was introduced, however, in this work, although some steps in that direction appeared to be in progress. PMID- 4020025 TI - Wild analysis. AB - Contemporary debates over psychoanalytic theory and practice warrant a reconsideration of the concept of wild analysis. Freud's initial formulation of the problem, subsequent developments in the Freudian conventions, and the work of Melanie Klein, Kohut, and Gill are compared in order to bring out different conceptions of interpretation that is wild, sound, or too tame. These different conceptions are system-bound. Moral implications of Klein's, Kohut's, and Gill's critiques and alternative systems are taken up. PMID- 4020026 TI - The object in psychoanalytic theory. PMID- 4020027 TI - Thoughts about early pathology. AB - In this paper, I have presented the assumption that some symptom pictures such as attachment to pain, the masochistic character, the negative therapeutic reaction, a basic depressive response, and anhedonia are rooted in a prevalence of organismic distress during the symbiotic phase. Neuroscientists taught us that early experiences are associated with the neuronal structuring of the developing brain, which then affects concurrent or subsequent reactions. In particular I followed Ginsburg's (1982) assumption of a neuronally, genetically given aggressive drive potential which influences and is influenced by early experiences, and which can interact with other gene potentials. In some patients aggressive drive components contributed to a less than harmonious basic core associated with failure of the early infant/mother interaction. Unpleasure prevailed during the symbiotic phase; aggressive energies predominated and enmeshed with the neuronal encoding, the early structuralization in both the neurophysiological and psychological meaning. Thus, the structuring of the function of internalization and the emerging self-object experience were disturbed from early on. This then continued to foster a proclivity for unstable (fusion and) diminished neutralization tendencies. As biological discharge phenomena evolve into vague psychological awareness, such an infant does not attain a sense of well-being, but rather attains a sense of "not-well-being" (Joffe and Sandler, 1965) which remains continuous or can be triggered--kindled- by any reactivating constellation, and the object is experienced as a source of unpleasure. This is in line with Mahler's bad mother and bad self-introjects. Primary narcissism has not evolved well or, said differently, is invested more with aggressive than with libidinal cathexis and is in an unfortunate association or balance with primary masochism. Aggressive drive components subsequently color fantasies, readiness for and severity of conflicts. The aggressivization of self feelings and of the function of internalization with its influence on--and exacerbation of--the rapprochement crisis is traced into later symptomatology. The basic pathology as described in this paper then compounds the oedipally derived problems. PMID- 4020028 TI - Empathy and psychoanalytic technique. AB - I have attempted to review the major psychoanalytic contributions to our understanding of empathy within the psychoanalytic situation. In doing so, I have discussed the relation between empathy and identification, reviewed aspects of the metapsychology of analytic comprehension, and have described the role of the analyst's evenly hovering attention in empathic responsiveness, as noted by several analytic investigators of empathy. The interrelations between empathy and countertransference have been described, and neutrality issues as they relate to empathy have been noted. Certain themes around the development of empathy have been grouped together and critically examined. The work of Kohut with regard to empathy has been discussed in relation to earlier psychoanalytic contributions of which it is an outgrowth and expansion. The changes in meaning and emphasis of empathic processes in Kohut's works have been described and critically reviewed. Empathy in its popular usage refers to the capacity of one person to communicatively partake, in a limited way, in the experience of another. In its differentiation from sympathy and pity, its noncritical or value-neutral character is emphasized. This description of empathy indicates its relevance to psychoanalytic technique, which shares many similar characteristics. Empathy is a general or superordinate term for many more specific aspects of the sensitive interpersonal interactions in the intimacy of relationships like the psychoanalytic one. Attempts to assign a particular psychoanalytic technical meaning to empathy or build clinical and developmental theory around empathy are limited by the multiple referents and generality of the concept. Empathy as a term has its place as descriptive of the analyst's emotional relatedness to the patient. It does not refer to any specific psychoanalytic technical intervention or theoretical construct; rather, it describes in a general way the sensitive, tactful, and experience-near way in which the analyst approaches the inner life of his patients. PMID- 4020029 TI - Aspects of the analysis of an adult son of deaf-mute parents. AB - This case demonstrates unique features connected with the parental deafness: the patient's anger toward women, his splitting of objects into all-good and all-bad, ease of regression, yearning for the symbiotic mother particularly as it was related to space as a transitional phenomenon into which he brooked no intrusion, his unique interests and creativity, his method of teaching, the shaping of the Oedipus complex by preoedipal trauma, and his feeling of entitlement with need to be treated as an exception. I have attempted to demonstrate the relation of the preverbal and preoedipal traumata, stemming from the deaf-mutism of the parents of a hearing child, to the patient's pathology, the shaping of his oedipal constellation, and character traits. I have described the compensatory ego functions that resulted in the development of creative, professional ability. Also, I have tried to demonstrate the complicated multiple overdetermination of his symptoms and aspects of his character formation. PMID- 4020030 TI - A case of phallic-narcissistic personality. AB - A case of phallic-narcissistic personality is presented to demonstrate the intermingling of oedipal and narcissistic transferences and to suggest a therapeutic rationale for the analytic treatment of similar cases. The therapeutic approach to dealing with the narcissistic configurations involves: Empathic and receptive listening to the patient's material relating to and reflecting narcissistic motifs. This early objective extends only to gaining access to the detailed scope of the narcissistic material in its multiple aspects. Clarifying and identifying the relevant narcissistic configurations, both superior and inferior aspects, so that the patient becomes increasingly aware of their pervasive influence, and increasingly able to identify the respective motifs. Interpretively linking the narcissistically inferior and superior configurations into a common gestalt, so that the patient comes to understand that these opposing aspects are mutually linked, defensively interconnected, and reciprocally reinforcing. Identification and interpretation of interlocking patterns of projection and introjection, particularly as they reflect and express narcissistic configurations. Modification of patterns of projection and introjection through the medium of the ongoing interaction (partly interpretive, partly extra-interpretive) that characterizes the relationship between analyst and patient. Patient projections are thus modified and replaced by more autonomous and adaptive introjections derived from the analytic relation that facilitate the alteration of pathogenic narcissistic formations. PMID- 4020031 TI - Psychoanalysis and psychiatry: models for potential future relations. PMID- 4020032 TI - Entero-pancreatic reflexes revealed by duodenal anesthesia in the dog. AB - This study was designed to improve our understanding of duodeno-pancreatic reflexes, the existence of which was suggested by the previous observation of a reduction in secretin-stimulated pancreatic secretion during local anesthesia of the duodenal mucosa. The effects on this reduction in secretin-stimulated secretion of cholinergic or adrenergic blocking agents (alone or in combination) and of truncal vagotomy, were studied in conscious dog with gastric and pancreatic fistulae. For each agent and for secretin alone in normal and vagotomized dogs, a comparison was made of pancreatic secretion with and without lignocaine anesthesia of the duodenal mucosa. Lignocaine reduced pancreatic secretion with secretin alone, and stimulated it during infusion of atropine. The changes in both protein bicarbonate secretion were blocked by pentolinium and by phenoxybenzamine whereas propranolol mainly blocked the effects on bicarbonate output. The effect of truncal vagotomy resembled that of atropine. These results suggest the existence of two enteropancreatic reflex mechanisms; an excitory cholinergic vagal reflex and an inhibitory, atropine-resistant non-vagal reflex. Both are blocked by pentolinium (a ganglion blocker) and by phenoxy-benzamine, suggesting the involvement of alpha-adrenergic receptors probably also at the level of the ganglion cell. Beta-adrenergic receptors are also involved in the regulation of bicarbonate and fluid secretion. PMID- 4020033 TI - A comparison of the autonomic nervous control of the heart during classical aversive vs appetitive conditioning in dog. AB - Dogs were trained in either classical (i.e. Pavlovian) appetitive (n = 7) or aversive (n = 7) conditioning by presenting a tone (the conditional stimulus, CS +) that was followed by either food or shock delivery, respectively. In the first case, dog food was given to the animals during the last 30 s of a 1 min CS+. Aversive conditioning was accomplished by giving a 1 s shock at the end of a 30 s CS+. The control consisted of a different tone (CS-) which was never followed by food or shock. A chronically implanted transducer was used to record left ventricular pressure from which its first time derivative was calculated; d(LVP)/dt was used as an index of myocardial inotropic state. Heart rate (HR) was also determined. These data were averaged over the 30 s prior to the CS+, the 30 s of the conditional stimulus tone itself, and the 30 s following shock or during food delivery. Well-trained animals evidenced changes in cardiac inotropism and chronotropism during the CS+ and also in response to unconditional shock or food; these are referred to as the conditional and unconditional cardiovascular responses, respectively. No statistically significant HR or d(LVP)/dt changes were observed during the CS-. The conditional response to food was small: relative to the pre-CS+ interval, average HR increased 11 bpm (P less than 0.05) and average d(LVP)/dt increased 309 mm Hg/s (P less than 0.01). During food delivery, HR increased by additional 23 bpm (P less than 0.01) and d(LVP)/dt increased by another 232 mm Hg/s (P less than 0.01). Beta-adrenergic blockade virtually eliminated the conditional HR and d(LVP)/dt response to food, indicating that both the chronotropic and inotropic changes during CS+ were due to elevated sympathetic drive. beta-blockade did not eliminate the unconditional HR response (+17 bpm, P less than 0.01), indicating that parasympathetic withdrawal has a mediating role in this persisting tachycardia. The conditional response to shock consisted of a 26 bpm increase in HR (P less than 0.01), while d(LVP)/dt increased 998 mm Hg/s (P less than 0.01). The beta-blockade reduced the HR conditional response to +8 bpm (NS) and essentially eliminated the increase in d(LVP)/dt. These data indicate that increases in cardiac sympathetic tone play a primary role in mediating the conditional cardiovascular response for both paradigms. Parasympathetic withdrawal, on the other hand, figures critically in mediating the unconditional response to food. PMID- 4020034 TI - Hemodynamic, behavioral and biochemical disturbances induced by an experimental cranio-cervical injury (whiplash) in rats. AB - Two days after an experimental whiplash performed on anesthetized Long-Evans female rats, without any direct blow to the head, we observed: (1) a hypotension (in supine position) (P less than 0.01), (2) a disturbance of the postural regulation of cerebral blood flow (P less than 0.01), (3) a disturbance of learning behavior characterized by decreased acquisition and retention (conditioned avoidance response and labyrinth tests), (4) an increase of the dopamine level (whole brain, cerebellum, thalamus + hypothalamus, corpus striatum and rest), (5) a decrease of the noradrenaline level in whole brain (P less than 0.05) and in the medulla oblongata but an increase in thalamus plus hypothalamus, hippocampus and corpus striatum, (6) an increased reactivity of the peripheral alpha and beta receptors, determined by analyzing the hemodynamic consequences of i.v. injection of norepinephrine or isoproterenol, (7) there was no modification of the brain content of water or of serotonin and (8) finally, the injured rats displayed a remarkably aggressive behavior, though this was not quantified. These results are in agreement with the hypothesis that a change in brain amines metabolism could explain the different functional effects of whiplash. We therefore believe that the postconcussion syndrome is not subjective and that the neck injury is primary in the determination of the syndrome. PMID- 4020036 TI - Sympathetic postganglionic pathways to the hind-limb of the rat: a fluorescent histochemical study. PMID- 4020035 TI - Potential types of response of the parasympathetic denervated human parotid gland to cholinergic ligands. AB - Investigation of functioning of human parotid salivatory glands, both normal and postdenervated, has demonstrated the presence of 5 main types of salivatory responses to cholinergic agonists and antagonists. Existence of various types of response has indicated the presence of different subpopulations of M-cholinergic structures that interact differently with the agents of cholinergic induction and blockade. Two subtypes function in the norm and they are conditioned by the presence of a double regulation; nervous and humeral. Three additional potential subtypes of response have been revealed only under conditions produced by various degrees of the gland's denervation. The data obtained relate to the nature of multireceptors or receptor states within the M-cholinergic system. PMID- 4020037 TI - The projection of vagal afferents on the cerebellar vermis of the cat. PMID- 4020038 TI - Ultrastructure and stereological analysis of nucleoli of rat nodose ganglion neuron during a 24-h period: a comparison with sympathetic neurons of rat superior cervical ganglion. AB - The nucleoli of rat nodose ganglion were investigated during a 24-h span (light span 07.00-19.00 h). The mean volume of nucleoli and that of their components, especially fibrillar centers considered to be the interphasic counterpart of nucleolus-organizing regions, were determined by stereological analysis. The quantitative data showed that (1) nucleoli volumes of rat nodose ganglion neurons did not oscillate diurnally but that (2) there were diurnal dimensional changes in the volume of their fibrillar centers which strongly suggest an ultradian rhythmicity. These results are different from those obtained in studies of superior cervical ganglion neurons, in which nucleoli and nucleolar components followed a circadian rhythm with peak values during daily periods of darkness. Although the nucleoli of these 2 kinds of neurons involved in autonomic nervous system reactions do not show the same behavioural patterns, the present data bring to light a new example of circadian fluctuation in nucleoli and describes their organization in this respect. PMID- 4020039 TI - Arterial pressure- and cardiac rhythm-related single-neuron activities in the nucleus reticularis gigantocellularis of the rat. AB - This communication presents an analysis of 531 extracellularly recorded spontaneously active nucleus reticularis gigantocellularis (NRGC) single-neurons in pentobarbital anesthetized rats, with particular reference to their cardiovascular-related activities. Fifty-nine percent of the gigantocellular neurons evaluated had temporal relationship with induced or spontaneous arterial pressure fluctuations. Twenty-eight percent of the NRGC neurons manifested definite discharge patterns and periodicity with reference to the cardiac cycle. It is discussed that these gigantocellular neurons may serve as a primary component of the cardiovascular regulatory mechanism. Alternatively, they may coordinate the necessary circulatory support for activities varying from respiration to somatomotor functions or sleep-wakefulness. PMID- 4020040 TI - [Stickler's syndrome or hereditary progressive arthro-ophthalmopathy]. AB - Hereditary Progressive Arthro-Ophthalmopathy was described for the first time by Stickler. The major features of the syndrome are: myopia with retinal detachment and blindness, bone and joint dysplasia with arthropathy, and hearing loss. The condition is autosomal dominant with strong expressivity. Findings of 11 patients from 3 families are reported here: they confirm that this syndrome can be considered as a severe connective tissue disease. PMID- 4020041 TI - [Hypereosinophilic syndrome with ocular involvement]. AB - The authors report a case of idiopathic hypereosinophilia with Loffler endocarditis in a 19 year old male. Retinal arteriolar occlusions were observed in the pre-equatorial region and documented by angiography. Histologic examination of the globes showed obliteration of the arterioles by a fibrinous coagulum without signs of vasculitis. Clinical data appears to suggest an embolic origin of the occlusions rather than thrombosis in situ. PMID- 4020042 TI - [Uveitis in acquired syphilis]. AB - Syphilis is a well-established cause of uveal disease and is thought to be responsible for several distinct types of intraocular inflammation. Four cases of acquired syphilitic uveitis are reported. The diagnosis was essentially based on the clinical picture, the elimination of other possible causes, the results of reliable blood immunologic tests eg, the TPHA, FTA and Nelson tests, and the rapid response to penicillin therapy. Evaluation of anti-Treponema pallidum antibodies in the aqueous humor does not contribute to the diagnosis of syphilitic uveitis. Two cases needed large amounts of penicillin (total dosage, 440 million units). Oral steroids were used to control the associated inflammatory reaction and to prevent a Herxheimer reaction. All the patients responded well to therapy. PMID- 4020043 TI - [Participation of the external carotid artery in orbital vascularization]. AB - The authors present the result of 70 dissections of the arterial vascular system of the orbit. The craniofacial junction is an important location because of possible anastomosis between the two carotid systems. These anastomosis can be situated at the meningeal level, palpebral and also inside the orbit cavity. The embryology of the encephalic vascular supply allows one to explain the possible dual origin of the orbital blood supply. This work shows the frequent participation of the external carotid artery to the orbital vascularisation by mean of three collateral branches: the infraorbital artery, a branch of the maxillary artery, partakes in the arterial supply of the inferior oblique muscle in 85,7% of cases. Usually, the inferior muscular artery which is a branch of the ophthalmic artery also partakes in this supply. In very exceptional cases (2 of 70) the infraorbital artery alone supplies the muscle. the lacrimal artery which can come from the external carotid system either from the middle meningeal artery or from the anterior deep temporal artery. This meningolacrimal artery can be either a solo lacrimal artery (17,14% of cases) or be associated with another classical lacrimal artery, from the ophthalmic artery (11,43%). These lacrimal arteries coming from the external carotid system have the following characteristics: they are thinner than classical arteries, they penetrate the orbit by their own orifice, the Hyrtl canal, and they can participate in the muscular vascularisation, especially of the lateral rectus. When these arteries are unique, most often they are encountered when the ophthalmic artery has undercrossed the optic nerve.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4020044 TI - [Subclinical alcoholic optic neuritis without vitamin deficiency]. AB - Vitamin B1, Folic acid Vitamin B12, whole blood Lead level, and plasma Zinc level were determined in 82 patients admitted to an alcoholism rehabilitation program. Each patient was examined for an optic neuritis. Thirty-two of the patients had sub-clinical abnormalities suggestive of optic neuritis like dyschromatopsias and/or field visual defects. No differences were found in the blood levels of Vitamin B1, Folic acid, and Vitamin B12 between the 32% affected and the 68% unaffected subjects. Moreover vitamins blood levels were found to be within the limits of normal values in both groups. A negative correlation between whole blood Lead levels and plasma Zinc levels was found. When an optic neuritis occurs the lead level tends to be higher and the Zinc lower. Abnormalities of the more usual alcoholism tests: gamma glutamyl Transpeptidase (gamma GT), mean red cell volume (V.G.M.) and glutamic Oxaloacetic transferase (T.G.O.), were more pronounced in alcoholics with optic neuritis. PMID- 4020045 TI - [Pathology of the vitreoretinal interface]. AB - This comprehensive review of vitreoretinal junction involvement in various diseases is classified according to the static and dynamic features of the pathology. Apart from hereditary conditions such as Wagner's and Stickler's diseases, juvenile retinoschisis etc., retino-vitreal adhesions in equatorial degeneration and either idiopathic or secondary epiretinal membranes are described. Vitreo-retinal caused either by trauma, by cellular contraction in epiretinal membranes or by posterior vitreous detachment may especially provoke peripheral retinal tears or macular involvement. PMID- 4020046 TI - [Contraception and the use of care systems]. AB - A study has been made of the frequency of the use of contraceptive methods and the methods used (oral contraception, intra-uterine device and other methods). This was carried out on 2000 women aged between 20 and 44 who had not been sterilised, were not pregnant, who lived in towns and in the country. The following variables were studied: the age, the socio-professional class, the zone in which they lived, the way antenatal care had been carried out (the number of antenatal visits and preparation for labour), the number of times they had seen a gynaecologist during the pregnancy, how the baby had been looked after in its first year of life and how often it had seen a paediatrician. A statistical analysis made it possible to categorise the variables that were studied in their relationship to medical contraception. This shows that as regards age, educational level and social status medical contraception was always better in towns than in the country. On the other hand, when women in the country do use medical contraception they go to the gynaecologist much more often than their town sisters do without any particular result from these consultations. Finally, medical contraception is not linked to other medical attention. This tends to confirm that contraception can be used as a prognostic element to show how well the woman will be looked after in pregnancy. PMID- 4020047 TI - [Cystometry: comparative values of water manometry and the "Mikro-Tip" method in the assessment of urinary stress incontinence]. AB - Urethro-cystometry carried out on 20 patients with urinary stress incontinence which was clinically apparent gives quite different results if it is carried out using the water manometry technique of Bech-Heidenreich or using a Mikro-Tip technique without perfusion. Comparing the two techniques shows: --little or no difference in the measurement of the functional length of the urethra and the maximum pressure of closure of the urethra. --no difference between the form of the urethral surface at rest and the bladder surface on effort. --on the other hand it shows a very definite difference in the urethral surfaces on effort which depends on the large differences occasioned by the transmission factor. The latter is weak with the Heidenreich method and corresponds to the clinical state; it is raised with the micro-tip method, which contradicts the clinical evidence. PMID- 4020048 TI - [Massive edema of the ovary: apropos of a case]. AB - A case of massive ovarian oedema is reported with a review of the literature. We would like to point out the value of thinking about the diagnosis of massive ovarian oedema when confronted with an ovary that seems to contain a tumour and to ask for frozen-section examination. By doing this the diagnosis can be made and the ovary preserved after the torsion has been dealt with in a young girl who is usually nulligravida. PMID- 4020049 TI - [Localized spontaneous cytosteatonecrosis of the breast]. AB - A clinical case of fat necrosis of the breast is reported. The main clinical, radiographical and ultrasonographical aspects are described and discussed. The importance of surgical biopsy is emphasized in the atypical cases. PMID- 4020050 TI - [Postoperative paralysis of the leg]. AB - Gynaecologists and bowel surgeons should realise that paralysis of the muscles of the lower limb following operation, although rare, is a definite risk which can be avoided by pre- and post-operative measures, especially as nowadays it is customary to operate through small narrow scars of aesthetic appearance. This does increase the risks, particularly when heavy retractors are used. PMID- 4020051 TI - [Gestational diabetes: the urgent need for a consensus]. AB - About 2% of all pregnant women are affected by gestational diabetes. Unfortunately there is no unanimity in considering the criteria for the definition, classification and screening of these patients. This work tries to sort out the principal elements to be found in the literature that could help to work out a consensus in this field. At the present time, one of the best definitions seems to be "any pregnant women in whom the onset or recognition of diabetes or impaired glucose tolerance occurs during pregnancy". So, gestational diabetes is not synonymous of White's Class A and it is suggested to restrict the White classification to the diabetic women who subsequently become pregnant. The diagnostic test to establish glucose intolerance will be the oral glucose tolerance test with 100 g glucose. Various sets of criteria have been suggested for the interpretation of this test but it is advisable to use normal values established by one of the prospective studies, either by O'Sullivan in the USA or by Pinget in France or by Abell in Australia. As far as screening is concerned, the most sensible, specific and easy strategy appears to estimate, in every pregnant woman, the plasma glucose level one hour after a load of 50 g and to restrict oral glucose tolerance tests to the pregnant women whose results is above 150 mg%. PMID- 4020052 TI - [Results of preparatory surgery for in vitro fertilization with embryo transfer]. AB - 68 cases out of a total of 407 patients who were destined to have IVF (16.7%) had most adhesions in the pelvis which made the ovaries inaccessible for laparoscopic recovery, in the two years between September 1981 and September 1983. Using very severe criteria for selection we rejected 46 cases as unsuitable for surgery at that time. Only 22 therefore remained to have preparatory surgery. This surgery was particularly aimed at improving the local conditions for laparoscopic recovery as well as improving the quality of ovulation. The results are encouraging because those women who were operated on had about the same level of success in the three stages of IVF as women who were not operated on. This three stage protocol of exploratory laparoscopy, operation and recovery laparoscopy does seem to be a heavy one and probably will be able to be replaced by a transvaginal ultrasound technique when this has been developed far enough to show that it has advantages. PMID- 4020053 TI - [Hysteroplasty for hemi-uterus and divided uterus. Apropos of 45 cases]. AB - The authors present a series of 45 plastic operations for bicornuate uterus. Three women were operated on for functional symptoms, eight for sterility of which seven were primary, and thirty four for infertility. They are sorry that three women were lost to follow up. They used the Bret-Palmer technique with modifications that they themselves describe. They justify this choice as against other techniques of metroplasty. The anatomical results are, in the main, good when controlled by hysterosalpingography 3 to 6 months after the operation. The functional results, by which is meant the pregnancies that have been obtained, are medium as far as sterility is concerned. Four out of the eight women who were operated on became pregnant. But they are very good in cases of infertility, because thirty out of the thirty four cases that were operated on had one or two pregnancies. The authors justify their indications for metroplasty after a first spontaneous abortion by the good results they have had, and because bicornuate uteri give rise to many obstetrical complications. Furthermore in unoperated cases there is often difficulty in attempting a new pregnancy, and quite often spontaneous late abortions or premature labours. In certain cases they carried out the operation after first spontaneous abortions, but they are more conservative in operating in cases of primary sterility. The authors do not think it is necessary always to carry out a cerclage procedure nor a caesarean operation automatically in cases that have become pregnant after metroplasty. PMID- 4020054 TI - [Peridural obstetrical analgesia using an electronic syringe]. AB - The authors present a study of 20 cases of epidural obstetrical analgesia. A Bupivacaine-Fentanyl mixture was given by continuous flow to bring about this analgesia. After an initial injection of 10 ml (9 ml of 0.25% Bupivacaine and 0.05 mg Fentanyl), a mixture of 45 ml of 0.25% Bupivacaine and 0.25 mg Fentanyl was perfused into the epidural space using an electronic pump syringe, delivering at a rate of 5 ml/hr. The mean time of analgesia until the delivery is 4 h 40 mn and the women in labour received a mean of 31.14 ml of 0.25% Bupivacaine (77.85 mg) and 0.173 mg Fentanyl. It took only 5 1/2 minutes to set up this form of analgesia. Not a single patient had any pain the first stage of labour nor in the second stage, and 95% of them were able to push efficiently. There are no detectable changes in the haemodynamic parameters in either the mothers or the fetuses and no depression of maternal respiration was found. In each case the Apgar score was 10 after 5 minutes. In summary, the use of an electronic pump syringe to deliver a Bupivacaine-Fentanyl mixture in obstetrical labour is a great improvement in analgesia without any secondary effects in the mother and child. PMID- 4020055 TI - The management of delayed union and nonunion of the metacarpals and phalanges. AB - Nonunion and delayed union of the tubular bones of the hand are uncommon occurrences, but are often associated with functional deficits. Twenty-five consecutive phalangeal and metacarpal nonunions and delayed unions in patients seen at the Massachusetts General Hospital were reviewed and classified by the criteria of Weber and Cech. Most of the patients treated had inadequate or improper primary Kirschner wire fixation. Secondary treatment depended upon the associated disability. In seven cases treatment was by bone excision, arthrodesis, or arthroplasty. No treatment was given in four cases. Fourteen patients had operations to gain skeletal union. Rigid skeletal fixation with plates or lag screws was used in seven cases and permitted rapid postoperative mobilization of soft tissue and joint. PMID- 4020056 TI - Comparison of internal fixation techniques in metacarpal fractures. AB - A biomechanical study assessed quantitative differences in the stability that was obtained by five commonly used types of internal fixation employed in metacarpal fractures. The techniques included dorsal plating, dorsal plating combined with an interfragmentary lag screw, crossed Kirschner wires, a single intraosseous wire combined with a single oblique Kirschner wire, and a single intraosseous wire alone. Rigidity and strength in torsion and bending were determined after transverse osteotomy and fixation of the metacarpal were performed. The failure modes for each fixation technique were also observed and described. Significant differences in rigidity were found between the plated configurations (with or without an interfragmentary lag screw) and the wired configurations in both apex dorsal bending and axial torsion. The three wired configurations were not significantly different from each other except in torsion. Analysis of the bending moments that were required to produce both yield and failure in apex dorsal bending and also the energy absorbed to yield showed similar disparity between plated and wired techniques. For metacarpal fixation, dorsal plating with or without lag screws provides significantly more stability than do wired techniques and approaches that provided by intact bones. PMID- 4020057 TI - Digital venous anatomy. AB - The veins of the digits and their valves were studied in nine cadaveric hands by sequential angiography, microdissection, routine histology, cross-sectional microradiography, and corrosion casting. The findings revealed a pattern of dorsal venous arches situated over each digit. Connections between those arches were at the level of the metacarpal heads, the point at which most of the palmar venous blood joins the dorsal system by intercapitular veins. A system of valves, which were arranged so as to direct flow from distal to proximal, from palmar to dorsal, and from radial to ulnar in the hand, was present in all veins as far distal as the pulp. PMID- 4020058 TI - Distal ulnar recession for disorders of the distal radioulnar joint. AB - Thirty-six wrists of 35 patients were treated with distal ulnar recession for pain and limitation of motion associated with chondromalacia of the ulnar head, triangular fibrocartilage complex tears, ulnocarpal impingement, and instability of the distal radioulnar joint. Contributing factors were positive ulnar variance in 31 wrists, fracture of the distal radius in five, sprains in 14, premature closure of the distal radial epiphysis in five, and lax ligamentous habitus in five. The ages of the patients averaged 33 years. Clinical findings were local tenderness, crepitus, and instability evident by a positive "piano key" effect. Roentgenographic findings were positive ulnar variance (29 of 36), zero ulnar variance (four), negative ulnar variance (three), positive arthrogram (11 of 19), and "forme fruste" Madelung's deformity (two). The surgical procedure is a modification of the Milch cuff resection with the use of a dynamic compression plate. Recession ranged from 2 to 13 mm (average of 4 mm). Findings at surgery included chondromalacia of the ulnar head (19), tears of the triangular fibrocartilage complex (11), and excessive mobility of the ulnar head (10). At an average follow-up of 24.5 months, results were excellent in 7 wrists, good in 21, fair in four, and poor in four. Poor results in two wrists were upgraded to good after osteosynthesis of a nonunion in one and recessional osteotomy of the radial sigmoid notch in the other. Ulnar recession offers a less destructive alternative to disorders of the distal radioulnar joint than the Darrach resection. PMID- 4020059 TI - The scaphotrapezial ligament complex: an anatomic and biomechanical study. AB - An anatomic and biomechanical study of the ligamentous stabilizers of the scaphotrapezial trapezoidal joint was performed in 25 fresh cadaver specimens. A consistent scaphotrapezial ligament complex consisting of four entities was identified. This complex is comprised of a stout scaphotrapezial ligament on the radial and palmar aspects of the scaphotrapezial joint, weak palmar and dorsal capsules, and a scaphocapitate capsular ligament. A biomechanical study subsequently found that these structures were directly related to resisting diastasis of the scaphotrapezial trapezoidal joint. This information is helpful in understanding scaphoid tuberosity fractures, scaphotrapezial instability and arthrosis, scaphoid dislocations, and perhaps scapholunate disassociations. PMID- 4020060 TI - Radiocarpal septum after trauma. AB - A case is presented in which trauma, followed by open reduction and pinning, resulted in the formation of a radiocarpal septum that divided the joint into two distinct compartments. A simple resection of the septum was not sufficient, since it uncovered underlying carpal instability that required ligamentous reconstruction. PMID- 4020061 TI - Bilateral traumatic dislocations of Volz total wrist arthroplasties: a case report. AB - Bilateral traumatic dislocations of Volz total wrist arthroplasties in a patient with rheumatoid arthritis occurred 7 years after the initial surgical procedures. Treatment consisted of closed manipulation and reduction of both wrists followed by temporary splinting. Good function was restored in both wrists without operative intervention. No fractures or loosening at the bone cement interface was encountered. PMID- 4020062 TI - Restoration of sensibility to anesthetic scarred digits with free vascularized nerve grafts from the dorsum of the foot. AB - Five cases of segmental vascularized nerve grafts that bridge scarred beds for digital sensory nerve reconstruction where previous nonvascularized nerve grafts have failed are reported. Average follow-up in this study was 27 4/5 months. Three patients were men and two were women. Average age was 35 1/2 years. The thumb was the recipient digit in one patient; the index finger in two patients; and the long finger in two patients (primary opposing digit). Three digits had suffered amputation and two had crush lacerations. Average graft length was 6.6 mm. Pin prick, touch, and vibratory sensation were restored in all patients (slightly impaired in one). Average moving two-point discrimination was 7.2 mm; average static two-point discrimination was 9.5 mm. Von Frey monofilament cutaneous pressure averaged 4.03 gm. Donor morbidity was negligible except for a neuroma in one patient and slight superficial skin loss in another. PMID- 4020063 TI - The overlap pattern of the lateral antebrachial cutaneous nerve and the superficial branch of the radial nerve. AB - The anatomic relationship between the lateral antebrachial cutaneous nerve (LABC) and the superficial branch of the radial nerve (SBR) is outlined in 53 cadaver and 41 clinical dissections. Either partial or complete overlap of the LABC with the SBR occurred in 75% of the cases. The LABC and the SBR innervated separate territories in only 25% of the dissections. We suggest that injury to the LABC may be a concomitant finding in patients with injury to the SBR and that this associated injury to the LABC may be one of the reasons why neuromas of the SBR have been thought to be more resistant to therapy than neuromas elsewhere. PMID- 4020064 TI - Partial dorsal wrist denervation: resection of the distal posterior interosseous nerve. AB - Chronic dorsal wrist pain limits hand function. This article details preoperative diagnostic nerve block and patient selection criteria, operative technique for partial dorsal wrist denervation, and results of nonoperative as well as operative treatment for pain transmitted via the distal posterior interosseous nerve. More than 90% of the patients treated with the partial dorsal wrist denervation procedure achieved subjective relief of pain and objective improvement in wrist function, with 83% returning to work. Function did not improve in the group with fractures associated with reflex sympathetic dystrophy, and three of the four patients with rotary subluxation of the scaphoid subsequently required wrist fusion. PMID- 4020065 TI - Streptokinase in the treatment of acute arterial occlusion of the hand. AB - Continuous, low-dose, intra-arterial streptokinase was used to treat six patients with ischemia of the hand secondary to distal arterial occlusion. A bolus dose of 100,000 U of streptokinase was administered, followed by a maintenance dose of 5000 U/hr, which was titrated against the patients' coagulation profile. The duration of infusion ranged from 16 to 96 hours. Recanalization was achieved in four patients who were treated within 36 hours of the onset of occlusion. PMID- 4020066 TI - Influence of vessel clips on vascular patency in microarterial grafts less than 0.5 mm in external diameter. AB - Autogenous interpositional microarterial grafting of 140 saphenous branches of albino rat femoral arteries with an external diameter of 0.3 to 0.5 mm (mean 0.45 +/- 0.06 mm) resulted in an immediate patency rate of 100%. The patency rate observed at 72 hours was 64.3%. The late patency rate was related to blade tip pressure of the double approximator clip used in the microanastomosis. The patency rate with a clip with a blade tip pressure of 22 gm was 52.7% and that with a clip with a blade tip pressure of 2 gm was 77.3%. When arterial occlusion lasted less than 30 minutes, the late patency rate was 76.9% to 78.3%. If arterial occlusion lasted for as long as 1 hour, the late patency rate of vessels occluded by a clip with a blade tip pressure of 22 gm dropped to 27.8%. These results demonstrate that an interpositional microarterial graft as small as 0.5 mm in external diameter is clinically feasible. PMID- 4020067 TI - A laser diffraction method for measuring muscle sarcomere length in vivo for application to tendon transfers. AB - A technique that uses laser light diffraction to measure muscle sarcomere length allows direct determination of optimal muscle length during tendon transfers. Forearm muscle sarcomere length with the hand in the position of function is 2.4, and muscle length corresponds directly to sarcomere length. We have used these observations to restore optimal muscle length during tendon transfers. Standard high radial nerve tendon transfers in six fresh cadaver forearms demonstrated the efficacy of the laser diffraction method in accurately measuring sarcomere length. In two clinical trials with the laser, standard high radial nerve palsy tendon transfers were performed. In each case the clinical tendency was to overpull the muscle during the transfer. With the laser it was possible to identify excessive muscle stretch and restore optimal muscle length. PMID- 4020068 TI - Surgery to achieve dynamic motor balance in adult acquired spastic hemiplegia: a preliminary report. AB - Reconstructive surgery of the upper limb was performed in an attempt to restore dynamic motor balance in 55 patients with adult-acquired spastic hemiplegia. An eight-level grading system was developed to determine the level of functional capacity. Because this system proved useful in predicting the results of surgery, it was utilized for operative planning. A two-level increase in functional grade was necessary for patients to obtain a meaningful increase in function. The average improvement after surgery was 2.10 functional levels. A two-level increase was achieved in 73.2% of the patients. No patient decreased in grade, and only one remained unchanged. In selected patients with upper limb spasticity, a predictable improvement in functional capacity can be obtained with dynamic motor balancing surgery. PMID- 4020069 TI - Redirection of extensor pollicis longus in the treatment of spastic thumb-in-palm deformity. AB - Twenty patients with the thumb-in-palm deformity associated with cerebral palsy were treated surgically by redirecting the extensor pollicis longus (EPL) tendon through the first dorsal retinacular compartment in association with releasing the spastic intrinsic thenar muscles at their origin. The redirected EPL tendon augmented extension-abduction of the thumb in all patients; 18 patients were able to grasp with the thumb outside the clenched fist and noted improvement in functional activities. Augmentation tendon transfer that uses the EPL is an ideal surgical treatment for patients with cerebral palsy who have a thumb-in-palm deformity, since the procedure relieves an adduction deforming force and augments the weak extension-abduction by means of a musculotendon transfer that is known to function during digital extension. Consequently, postoperative reeducation of the transfer is minimal. PMID- 4020070 TI - Toe-to-hand transfer based on the medial plantar artery. AB - Two patients had toe-to-hand transfers based on the medial plantar artery system. The dorsalis pedis and first dorsal metatarsal arteries were absent in both cases. Although the procedure is slightly more complicated than currently described techniques for toe-to-hand transfers based on the dorsal system, the procedure was performed in both cases without complication. PMID- 4020071 TI - A palmar cross-finger flap for coverage of thumb defects. AB - We have devised a method of covering tissue defects of the distal thumb using a flap elevated between the two flexion creases on the palmar skin over the proximal phalanx of the long finger. The advantages of this method over the usual dorsally based, distal, cross-finger flap include improved appearance of the donor finger, comfortable positioning, and avoidance of joint contractures. Although sensitivity of the palmar scar, contractures, or other disadvantages of this approach were sought during follow-up, none were found. PMID- 4020072 TI - Flexor tendon gliding in the hand. Part I. In vivo excursions. AB - The amplitude of gliding of the flexor tendons was measured in 36 hands tagged intraoperatively with buried wire sutures. Finger and wrist position was correlated with tendon excursion as measured on radiographs in the postoperative period. With the wrist in the neutral position, the superficialis tendon achieved an excursion of 24 mm and the profundus tendon 32 mm. Excursion of the flexor pollicis longus tendon was 27 mm. With wrist range of motion, the amplitude of the superficialis tendon became 49 mm, the profundus tendon 50 mm, and the flexor pollicis longus tendon 35 mm. PMID- 4020073 TI - Flexor tendon gliding in the hand. Part II. Differential gliding. AB - Flexor tendon gliding was studied in vivo in 48 hands. Three finger motions- straight-fist, hook, and fist--were found to provide maximum differential gliding for superficialis and profundus tendons in respect to each other, as well as in respect to the flexor sheath and bone. PMID- 4020074 TI - A method for evaluating carpal alignment on lateral radiographs. AB - An alternate method of diagnosing carpal instability has been presented. The apparatus is easy to construct and is inexpensive. If the apparatus is used properly, it will enable the technician to obtain consistent and comparable radiograph projections. The use of a clear plastic rule with concentric circles is optional but may assist in a more accurate centering of the capitate and lunate circles. PMID- 4020075 TI - Reduction and fixation of phalangeal fractures. PMID- 4020076 TI - Heuristic approaches to decision-making in the delivery of primary health care within developing regions. AB - The delivery of primary health care (PHC) services is now recognized as a crucial element in the development of low-income regions. Effective delivery of these services requires the ability to solve a variety of policy decision problems. Research has demonstrated the utility of operations research/management science (OR/MS) models and methodologies in the analysis and solution of such problems. However, this approach may be limited in some regions by the data and computational requirements of the models. Intuitive approaches in the spirit of OR/MS models, termed heuristics, can provide an effective alternative in such cases. The current paper proposes a general heuristic procedure for solving problems of PHC delivery in developing regions. The heuristic is applied, in detail, to the problem of identifying "best" community financing schemes for PHC services in low-income sections of Rio de Janeiro, Brazil. PMID- 4020078 TI - Sounding bored--the bedside manor! PMID- 4020077 TI - Politics and bioethical commissions: "muddling through" and the "slippery slope". AB - When they have addressed highly controversial subjects, the bioethical commissions of the last decade have tended to avoid explaining the ethical justifications for their recommendations. This omission is consistent with the typical preference of policymakers for "muddling through," because it is often possible to reach agreement on specific decisions even when disagreeing sharply on principles. In bioethical policy, this omission of reasons has some special consequences. It allows commission members to ignore "slippery slope" arguments, which are based on the claim that the logic of justification adopted to address the current problem will ultimately lead us to great harms. Case-by-case decision making--along with the omission of reasons for decisions--will tend to highlight the benefits of innovation, and downplay possible long-term effects that might be ethically upsetting. PMID- 4020079 TI - Why does cholesterol ever precipitate out of human bile? PMID- 4020080 TI - Endoscopic tape dilator--a simple and inexpensive method to dilate upper gastrointestinal strictures. AB - Adhesive tape wound around the shaft of an upper GI endoscope serves as a simple method to dilate upper GI strictures under endoscopic control. This technique avoids the need for guidewires and fluoroscopy. PMID- 4020081 TI - Delayed gastric emptying in children with Crohn's disease. AB - To evaluate the role of delayed gastric emptying in the decreased nutritional intake and growth retardation of some patients with Crohn's disease, we looked at four groups: 1) Crohn's disease with growth retardation; 2) Crohn's disease with malnutrition or acute weight loss; 3) Crohn's disease without growth retardation or malnutrition; and 4) normal controls. Gastric emptying was measured by a test meal incorporating 99mTc sulfur colloid-labeled chicken liver as the solid phase marker and 111In-labeled water as the liquid phase marker. The percent of each isotope retained in the stomach over 120 minutes was compared among the groups and correlated with established nutritional parameters, caloric intake, and disease activity. Gastric emptying of the liquid component was the same in all groups, and emptying of solids in patients with Crohn's disease and growth retardation was not significantly different from controls. However, gastric emptying of solids was delayed in five of seven patients in the malnourished group; the mean emptying rate of all seven patients was significantly slower compared both to the normals (p less than 0.01) and the Crohn's patients without growth disturbances (p less than 0.05). This delay was correlated with caloric intake, but not with disease activity or any individual nutritional parameter except arm muscle area (p less than 0.01). Multiple regression analysis revealed that 54% of the variation in the emptying of solids could be accounted for by nutritional factors. Fifty-seven percent of patients with delayed gastric emptying had radiologic and/or endoscopic evidence of nonconstrictive involvement of the duodenum with Crohn's disease, while 80% of patients with such involvement had delayed gastric emptying. These results help explain the decreased caloric intake observed in Crohn's disease patients and support the role of liquid caloric supplements. PMID- 4020082 TI - Should we worry about gastric cancer in duodenal ulcer patients? AB - In three patients with active duodenal ulcer, carcinoma of the stomach was detected early during routine endoscopic examination. In all patients subtotal gastrectomy was performed, and pathological examination of the resected stomach revealed carcinoma confined to the mucosa. We review evidence for and against any association between gastric carcinoma and peptic ulcer disease. PMID- 4020083 TI - Charcot-Leyden crystals. AB - Charcot-Leyden crystals are associated with the active proliferation of eosinophils and are nonspecific. PMID- 4020084 TI - Salmonella infections complicating inflammatory bowel disease. AB - One hundred and five of 267 patients with inflammatory bowel disease at a community hospital had recorded diarrhea, but only one had Salmonella (0.9%). Two additional patients, one from another institution, are also reported. A literature review disclosed only 37 cases, 18 of which were adequately defined clinically. Patients with IBD may not be at an increased risk for Salmonella infection. Salmonella infection may increase the severity of IBD, and therefore antibiotics may be necessary. PMID- 4020085 TI - Acute colonic pseudo-obstruction: a possible role for the colocolonic reflex. AB - In diverse clinical settings, injury or impairment of the peripheral autonomic nervous system may cause acute colonic pseudo-obstruction. The mechanism has remained elusive since Ogilvie's original description. In classic Ogilvie's syndrome, colonic pseudo-obstruction is associated with malignant invasion of the prevertebral ganglia, and may be mediated through the colocolonic reflex, described in a guinea pig model. We have treated three patients with acute colonic pseudo-obstruction due to: 1) malignant invasion of the prevertebral plexus (classic or true Ogilvie's syndrome), 2) clonidine, and 3) herniorrhaphy under epidural anesthesia. In this paper, we discuss the possible role of the colocolonic reflex in the pathophysiology of acute colonic pseudo-obstruction, and the delineation of true Ogilvie's syndrome from the other many causes of acute colonic pseudo-obstruction. PMID- 4020086 TI - Giant hamartoma of the colon: Peutz-Jeghers type. AB - We have seen a young man with multiple large-bowel polyps and a single immense colonic polyp of the Peutz-Jeghers type. It was completely removed primarily to control hemorrhage and to exclude focal adenomatous or carcinomatous change. We review the spectrum of colonic hamartomas. PMID- 4020087 TI - Healing of endoscopic biopsy sites in the human rectum. AB - The time required in man for a rectal ulcer created with endoscopic biopsy forceps to heal is unknown. To answer this question, we created a large ulcer (approximately 8 mm in diameter) and a smaller ulcer (approximately 4 mm in diameter) in four healthy young men and followed the healing of the ulcers by visual examination every 4 days. Complete healing of the large ulcer had not occurred on days 4 and 8, while by day 12, three had healed and by day 16, all four had disappeared. Of the small ulcers, two had healed by day 8, and all had healed by day 12. This study suggests that it takes approximately 8-12 days for an artificially created rectal lesion to heal completely. PMID- 4020089 TI - Gastric outlet obstruction secondary to a gallstone (Bouveret's syndrome) PMID- 4020088 TI - Hepatic abscesses associated with Crohn's disease detected by 111Indium leucocyte scanning. AB - An asymptomatic woman with Crohn's colitis developed an ESR of 92 and was found by 111Indium leucocyte scanning to have two hepatic abscesses. Their early detection led to successful treatment. PMID- 4020090 TI - Obstructing lipomas of the esophagus and ileocecal valve. PMID- 4020091 TI - Ultrasound augmentation of central nervous system tumor therapy. PMID- 4020092 TI - Childhood thoracic trauma. PMID- 4020093 TI - 'Asanguinous' open-heart surgery. PMID- 4020095 TI - Ethics and medicine. 2. The Hospital Medical Ethics Committee. PMID- 4020094 TI - Skin diseases: current concepts, therapy. 2. Psoriasis. PMID- 4020096 TI - Hey, maximus, off your gluteus! PMID- 4020097 TI - A fixation procedure suitable for autoradiography of endogenous long-chain acyl carnitine. AB - A tissue processing procedure was evaluated for fixation of endogenous long-chain acyl carnitine (LCA) to facilitate autoradiographic subcellular localization of this amphiphile. Suspensions of neonatal rat myocytes labeled with exogenous 14C palmitoyl carnitine retained 85.2% of the radiolabel after tissue processing. Autoradiography demonstrated no significant translocation of radiolabeled LCA from myocytes to unlabeled sheep erythrocytes mixed in equal proportions and processed together. To evaluate endogenous LCA fixation, cultured myocytes were incubated for 3 days with 3H-carnitine. Radioactivity was distributed in LCA, short-chain acyl carnitine, and free carnitine pools in proportion to the physiological concentrations of the metabolites traced. Before tissue processing, LCA contained 4.5% of total radioactivity. After tissue processing, labeled water soluble components were lost and 88% of the retained radioactivity was in the LCA pool. The enrichment of endogenous LCA radioactivity was attributable to the selective extraction of endogenous short-chain and free carnitine. Nearly 75% of endogenous LCA was preserved. In contrast, 99.5% of both endogenous short-chain and free carnitine were extracted. Thus, endogenous LCA can be selectively preserved, permitting quantitative subcellular localization of this amphiphile with ultrastructural autoradiography. PMID- 4020098 TI - Transfer of label from 3H-glucose in Digitaria eriantha leaves to the rust fungus Puccinia digitariae Pole Evans. AB - Digitaria eriantha pentzii was fed 3H-glucose prior to inoculation with uredospores of Puccinia digitariae Pole Evans. Twenty-one hours after inoculation, uptake of label from 3H-glucose by the primary infection structures of P. digitariae was demonstrated employing autoradiography. These results indicate that an exchange of nutrients between host and pathogen occurs very early on in the infection process, during the formation of the primary infection structures. Despite contrary reports that obligate parasites receive no nutrition before establishment of haustoria, this study supports the work of Andrews (Can J Bot 53:1103, 1975), who demonstrated uptake of 3H-glucose label from lettuce cotyledons into the primary and secondary infection vesicles, appressoria, and germ tubes of Bremia lactucae. PMID- 4020099 TI - Application of Nile red, a fluorescent hydrophobic probe, for the detection of neutral lipid deposits in tissue sections: comparison with oil red O. AB - Nile red is a phenoxazone dye that fluoresces intensely, and in varying color, in organic solvents and hydrophobic lipids. However, the fluorescence is fully quenched in water. The dye acts, therefore, as a fluorescent hydrophobic probe. We utilized this novel property of nile red to develop a sensitive fluorescent histochemical stain for tissue lipids. Nile red was prepared by boiling Nile blue A under reflux for 2 hr in 0.5% H2SO4, and extracting the product into xylene. For staining, the purified dye is dissolved in 75% glycerol (1-5 micrograms/ml) and applied to frozen tissue sections. Tissue lipids then fluoresce yellow-gold to red, depending on their relative hydrophobicity. Using sections of liver and aorta from a cholesterol-fed rabbit, we assessed the value of Nile red as a stain for neutral lipids by comparing the staining pattern obtained with that produced by oil red O, a commonly used dye for tissue cholesteryl esters and triacylglycerols. In the cholesterol fatty liver, Nile red staining was comparable to that of oil red O. In contrast, Nile red staining of rabbit aortic atheroma revealed ubiquitous lipid deposits not observed with oil red O staining. These latter results suggest that Nile red can detect neutral lipid deposits, presumably unesterified cholesterol, not usually seen with oil red O or other traditional fat stains. PMID- 4020100 TI - Intragranular colocalization of immunoreactive methionine-enkephalin and oxytocin within the nerve terminals in the posterior pituitary. AB - To determine differential tissue antigens in the same section immunocytochemically using the electron microscope, the neurohypophysis was examined following the application of a freeze-drying tissue preparation and staining with the protein A-colloidal gold-antibody complex method (Hisano S, Adachi T, Daikoku S: J Histochem Cytochem 32:705, 1984). At the light microscopic level, colocalized immunostaining for methionine-enkephalin (ENK) and oxytocin (OXT) was found in the rat neurohypophysis under different physiological states. Small pieces of the neurohypophysial tissue were frozen and dried. The dried tissue was fixed with paraformaldehyde vapor and embedded. The ultrathin sections were stained with the antibody for ENK coupled with protein A-small colloidal gold, and antibody for OXT or vasopressin (VP) conjugated with protein A-large colloidal gold. The ultrastructures of the nerve terminals were well preserved and showed many membrane-limited secretory granules. It was possible to identify both OXT- and VP-containing nerve terminals as their secretory granules were differentially labeled with protein A-colloidal gold anti-OXT or anti-VP complex, respectively. The secretory granules, which were labeled with large gold particles for OXT, also carry small gold particles. It is evident that ENK coexists with OXT in the same granules. PMID- 4020101 TI - Localization of binding sites for concanavalin A, Ricinus communis I and Helix pomatia lectin in the Golgi apparatus of rat small intestinal absorptive cells. AB - Binding sites for concanvalin A (Con A), Ricinus communis I agglutinin (RCA I), and Helix pomatia lectin (HPA) were localized in the Golgi apparatus of rat small intestinal absorptive cells. A preembedment technique, a modification of the one originally used by Bernhard and Avrameas (Exp Cell Res 64:232, 1971), was employed, with horse-radish peroxidase being used for cytochemical visualization. Incubations were performed on 10 microns thick cryosections of duodenal segments that were fixed in a mixture of 4% formaldehyde and 0.5% glutaraldehyde; fixation was preceded by a 2-min rinse in 0.1 M sodium cacodylate and followed by storage in the same buffer for up to 7 days. Incubation with Con A, which binds preferably to alpha-D-mannose and alpha-D-glucose residues, caused intense reaction of the dilated cisternae of the cis Golgi side; staining was variable in intermediate and trans cisternae. RCA I, recognizing beta-D-galactose residues, could only be demonstrated in intermediate cisternae. Reaction for HPA, which indicates alpha-N-acetyl-D-galactosamine residues, stained intensely 1 to 2 cisternae of the cis Golgi side, as well as being localized in the peripheral regions of the cisternae of the intermediate compartment of the stacks. Deposits of reaction product covered the luminal surface of the cisternal membranes, but usually left the lumen itself, as well as lipid particles, devoid of reaction. The differences in Con A, RCA I, and HPA reactivity between cis, intermediate, and trans cisternae suggest compositional and structural differences of the carbohydrates in the respective compartments; they may reflect conversion processes that are known to occur in the oligosaccharide side chains of glycoconjugates at the Golgi complex level. PMID- 4020102 TI - Immunoelectron microscopic localization of estrogen receptor with monoclonal estrophilin antibodies. AB - The recent production of a series of monoclonal estrophilin (estrogen receptor) antibodies recognizing estrogen receptor derived from a wide variety of animals and target tissues permits the development of immunoelectron microscopic techniques for identifying estrogen receptor. We have determined suitable conditions for the ultrastructural localization of estrogen receptor in tissue sections. Localization of receptor was observed in the euchromatin, but not in the marginated heterochromatin or nucleoli of epithelial and stromal nuclei of human endometrium. Competition studies indicate that only estrogen receptor specifically inhibits nuclear staining. The absence of any specific cytoplasmic localization at the electron-microscopic level is consistent with earlier light microscopic observations and suggests that the majority of the cellular pool of estrophilin exists in the nucleus of hormone-responsive cells. PMID- 4020103 TI - Horseradish peroxidase: factors affecting its distribution after retrograde infusion into the rat parotid gland. AB - Previous studies have shown that tight junctions of the unstimulated rat parotid gland are impermeable to retrogradely administered tracers such as myoglobin. Permeability is increased following beta-adrenergic stimulation, allowing the tracers to reach the intercellular and interstitial spaces. Reaction product of retrogradely infused horseradish peroxidase (HRP) and lactoperoxidase in found in the intercellular and interstitial spaces in both resting and stimulated glands, and many acinar and duct cells contain diffuse cytoplasmic reaction product. In this study we investigate several factors that might influence the distribution of HRP in the parotid gland. Tracer distribution was similar with HRP obtained from different suppliers, with different HRP preparations (Sigma types II, VI, VIII, and IX), and at HRP concentrations of 0.1-10 mg/ml. Inclusion of various saccharides in the infusion solution had no effect on the distribution of reaction product. Inhibition of the enzymatic activity of HRP by extraction of the heme group or reaction with hydrazine reduced but did not eliminate the extraluminal and cytoplasmic reaction product. In contrast, HRP treated with high H2O2 concentrations (0.04 M) was retained in the lumina and cytoplasmic staining was nearly abolished. Immunofluorescent localization of untreated and H2O2 treated HRP after retrograde infusion confirmed the findings obtained using diaminobenzidine procedures. These results suggest that the peroxidatic activity of HRP may damage cell membranes and tight junctions in the rat parotid gland, and indicate that permeability studies employing HRP as a tracer should be interpreted with caution. PMID- 4020104 TI - Optimal antigen localization in human tissues using aldehyde-fixed plastic embedded sections. AB - Although the utility of antigen labeling techniques in frozen tissues is well known, it is generally acknowledged that an improvement in morphologic preservation is desirable. Conventionally processed paraffin-embedded tissues are limited in the range of antigens that can be detected and newer plastic embedding techniques have been even more restricted. By using cold (4 degrees C) processing and limited fixation a wide range of antigens (including T and B markers) has been demonstrated in 2 mu plastic sections. The morphologic preservation and antigen localization are superior to other techniques. The combination of precise antigen localization and excellent morphologic preservation should expand the diagnostic and investigative uses of immunohistology. PMID- 4020105 TI - Biotypes and serotypes of thermophilic campylobacters isolated from cattle, sheep and pig offal and other red meats. AB - In this study we examined 730 faecal samples of offal (mainly liver), mince-meat and sausage meat collected from abattoirs and retail butchers' shops for campylobacters. Campylobacter jejuni or C. coli were isolated from 30.6, 10.5 and 6% of sheep, cattle and pig offal samples respectively. Specimens collected from abattoirs were, in general, more often contaminated than material obtained from retail butchers' shops. Only 1.4% of minced meats and sausage meats contained campylobacters. Most isolates (89.5%) were C. jejuni biotype 1 (Skirrow & Benjamin, 1980) of serotypes 1 and 2 (Penner & Hennessy, 1980). This study shows that animal offal is frequently contaminated with C. jejuni of biotypes and serotypes commonly isolated from human beings with campylobacter enteritis. PMID- 4020106 TI - The effect of surgical gowns made with barrier cloth on bacterial dispersal. AB - A dispersal chamber (body box) technique has been used to compare bacterial dispersal from the skin of subjects carrying out a stepping test under controlled conditions while wearing four differing garment systems namely: basic underwear, cotton 'blues' (standard pyjama style jacket and trousers for men or dress for women), ankle socks, boots for men and shoes for women, mask and theatre hat; the basic set covered with a cotton gown; the basic set covered by a gown with a front made from GORE-TEX fabric in which an expanded polytetrafluoroethylene membrane is sandwiched between layers of woven or knitted polyester; the basic set covered with a fully enclosed suit of the same fabric. A slit sampler was used to measure the number of bacteria liberated in a downward current of air. Six subjects (three female and three male) were studied. Males liberated more bacteria. Covering the 'blues' with a cotton gown increased the bacterial count; a gown of the new material reduced the increase by 50%, and the suit cut the dispersal to virtually zero. Preliminary work suggests that GORE-TEX garments survive laundering better than cotton, and may be cost-effective, but are not yet as comfortable. Research is presently in progress to improve this aspect. PMID- 4020107 TI - Salmonella isolation with Rappaport-Vassiliadis enrichment medium seeded with different sized inocula of pre-enrichment cultures of meat products and sewage polluted water. AB - A total of 574 samples, of seven different types, were examined for the presence of salmonellas. All the specimens were pre-enriched in buffered peptone water and enriched in Rappaport-Vassiliadis medium (RV medium). In one trial 0.1 ml of pre enrichment culture of 497 samples (79 chicken carcasses, 228 specimens of minced meat, 100 pork sausages, 19 samples of dried powdered chicken meat, 11 specimens of faeces of healthy pigs and 60 samples of sewage polluted natural sea water) was seeded to 10 ml as well as to 100 ml of RV medium. With the first inoculum (ratio 0.1:10), 111 samples were found to contain salmonellas, while with the second inoculum (ratio 0.1:100), only 102 positive samples were detected. This difference is marginally significant (P less than 0.05). In another trial, 0.1 ml, 0.2 ml and 0.5 ml of pre-enrichment culture of 162 specimens (71 chicken carcasses, 40 samples of sewage polluted sea water and 51 samples of sewage polluted river water) were in turn introduced to 10 ml of RV medium. With the 0.1 ml inoculum 93 positive samples were detected, while with the 0.2 and 0.5 ml inocula 93 and 88 positive samples were found. The differences are not statistically significant. In these trials the growth of competing organisms was minimal with ratios of inocula 0.1:10 or 0.1:100. PMID- 4020108 TI - A survey of Campylobacter in animals. AB - A survey of Campylobacter species in the faeces or rectal contents of domestic animals was carried out using direct and enrichment culture methods. Campylobacters were isolated from 259 (31%) of 846 faecal specimens. The highest isolation rate was found in pigs (66%); lower rates were found in cattle (24%) and sheep (22%). In pigs all the isolates were C. coli, in sheep and cattle about 75% were C. jejuni. Only five isolations of C. fetus subsp. fetus were made, all from cattle. More pigs with diarrhoea had C. coli in their faeces than healthy pigs (77% vs 47%), but such a clear difference in isolation rate between sick and healthy animals was not seen in cattle or sheep. The enrichment method increased the total isolation rate of C. jejuni and C. coli by 33%, but for cattle specimens it increased it by 69% (from 6.5% to 21%). However, the enrichment method failed to detect 16% of positive specimens (mainly C. coli), so direct and enrichment methods should be used for the culture of campylobacters from animal faeces. The results show that cattle, sheep and pigs constitute a large potential source of campylobacter infection for man. PMID- 4020109 TI - Prevalence of antibody against influenza A viruses in the Kren-Akorore, an Indian tribe of Central Brazil, first contacted in 1973. AB - Influenza A antibodies in serum samples obtained in 1980 from two Indian populations in Central Brazil were compared. The Kren-Akorore, who were first contacted in 1973 and two years later transferred to the Xingu Indian Park (PIX), were compared with Indians from other tribes already living in the PIX before 1975. An analysis was made of the prevalence and distribution of antibodies against the influenza A viruses which have circulated in the civilized world since 1918. Antibodies to the early influenza A viruses were absent in both Indian populations, but A/Hong Kong/1/68 (H3N2) virus apparently circulated in the PIX. No antibody to influenza A/Bangkok/1/79 or to A/Brazil/11/78 (H1N1) was found in any of the sera, whereas antibodies to these viruses were commonly found in urban populations in Brazil. The evidence from influenza antibodies agrees with the information that the Kren-Akorore Indians had been living in complete isolation until 1973, when they were first contacted. PMID- 4020110 TI - A study of the host range and distribution of antibody to Akabane virus (genus bunyavirus, family Bunyaviridae) in Kenya. AB - Serum neutralizing antibody to Akabane virus (genus bunyavirus, family Bunyaviridae) was found in a high proportion (50-95%) of cattle sampled in Kenya, while sheep and goats had fewer positive (13-33%). Camel and horse sera also contained antibody to the virus (70% and 50% respectively). The antibody was found in animals from the high altitude temperature type of grasslands, drier bushed and wooded grasslands and the semi-desert. No arthrogryposis nor hydranencephaly has been encountered in Kenya which might be related to this widespread virus infection. A wide range of Kenyan wild ruminants had antibody to Akabane virus in their sera, as also did zebra. PMID- 4020111 TI - An epidemiological study of Salmonella montevideo by biotyping. AB - Among 622 cultures of Salmonella montevideo, 27 biotypes belonging to two biogroups were recognized. One biogroup (10di) was predominant in all animals in Scotland but only in sheep in England and Wales. The other (biogroup 2d) was responsible for almost all human, cattle and poultry infection in England and Wales, but only 24% of human infection in Scotland. PMID- 4020112 TI - A comparison of virulence of two strains of Legionella pneumophila based on experimental aerosol infection of guinea-pigs. AB - Two strains of Legionella pneumophila (LP) serogroup I, of differing virulence, were examined in terms of numbers of viable organisms in tissues, pyrexia and mortality following aerosol infection. The Corby strain was the more virulent, with pyrexia and deaths of guinea-pigs 3 to 6 days after infection. This strain multiplied very rapidly in the lungs to reach a peak of 5 X 10(11) viable organisms/lung. Organisms were present in the blood, liver, spleen and kidney. The Philadelphia-1 strain (NCTC 11192) was unable to replicate in the lung and was cleared between 14 and 21 days after infection. Pyrexia was not observed. No guinea-pigs died and viable LP was not found in any organ other than the lung. Lung lavages on aerosol infected animals were performed and the virulent Corby strain was found to be mainly intracellular. The avirulent Philadelphia-1 strain was found predominantly in the extracellular location. There were approximately 10 times the number of viable virulent LP in the lung macrophage fraction than in the lung PMNL fraction. In comparison, there were approximately equal numbers of the viable avirulent strain in the macrophages and the PMNL. Experimental evidence suggests that the macrophage preferentially supports the growth of the virulent Corby strain compared with the PMNL. The avirulent strain on the other hand appears to be destroyed by both the macrophages and the PMNL. PMID- 4020113 TI - The interplay of host and organism factors in infection of the mouse genital tract by Mycoplasma pulmonis. AB - Mice of strain TO, in groups of ten, were inoculated intravaginally with Mycoplasma pulmonis organisms. Seven mice became infected after inoculation of organisms with strong haemadsorptive capacity, four after inoculation of organisms with diminished adsorptive capacity following ten passes in medium, and none after inoculation of apparently non-adsorbing organisms which had been passed 50 times. There appeared to be a correlation, therefore, between the ability to infect and the cytadsorptive capacity of the organisms. There was only a minimal vaginal polymorphonuclear leucocyte (PMNL) response in the infected mice and most of them had ceased to be infected by 35-42 days. In contrast, mice treated with progesterone had enhanced infections; all those given strongly haemadsorbing organisms, and organisms passed ten times, became infected and remained so for at least 42 days. Furthermore, at least ten fold more organisms were recovered from progesterone-treated than from untreated mice, and the PMNL response was much greater. Most of the progesterone-treated mice given organisms passed 50 times did not become infected, but some did, and the organisms recovered from them were fully cytadsorptive. It is postulated that a few cytadsorbing organisms in this inoculum were induced to infect under the enhancing effect of progesterone. PMID- 4020114 TI - Comparison of the impact of continuous and intermittent exposure to vinyl chloride, including phenobarbital effect. AB - Rats were subjected to 4 h continuous and intermittent exposure to vinyl chloride (VC) at the time-weighted average concentration of 50,000 mg/m3. Prior to exposure, half of the animals obtained water, whereas the other half 0.1% sodium phenobarbital (PB) solution for seven consecutive days. The studies were focussed on: body weight, liver weight, activity of enzymes in the blood serum, activity of glutathione S-transferase in the liver cytoplasmatic and microsomal fraction, content of free non-protein sulfhydryl groups (NPSH) in the liver and urinary excretion of thiodiglycolic acid (TDGA). VC exposure, both continuous and intermittent, resulted in a decrease of body weight, NPSH depletion in the liver and TDGA urinary excretion. PB effects were manifested by the persistent decrease in rats' body weight, increase in the liver weight, increase in the cytoplasmatic activity of glutathione S-transferase in the liver and increase in TDGA urinary excretion. With none of the tested parameters, except TDGA, statistically significant differences between the continuous and intermittent VC exposure at the same time-weighted average concentration of 50,000 mg/m3, were found. TDGA urinary excretion was higher in rats poisoned in continuous exposure, as compared to the intermittent one. PMID- 4020115 TI - Behavioral teratology--results achieved and perspectives of development. AB - The objective of behavioral teratology is to throw light on the consequences of prenatal effect of the agent on varying aspects of the functional state of the nervous system. In the present paper, the author proposes Carbendazim as a model of Type 1 behavioral teratogen (agent provoking morphological anomalies in the CNS). On this model, the author studied the sensitivity of a group of primary screening tests proposed in the literature, introducing semiquantitative and quantitative criteria for determining the level of response. The study of the postural reflex and behaviour in the open field were found to be the most sensitive. The latter also provides the possibility of demonstrating some qualitative deviations in behaviour, such as the "jumping" gait. PMID- 4020116 TI - Mercapturates in the urine of persons exposed to N,N-dimethylformamide. AB - N,N-dimethylformamide, a nucleophilic aprotic dipolar solvent, has multipurpose uses, especially in the manufacture of plastics. Its acute toxicity for mammals is low; it is hepatotoxic. Vapors are absorbed by the lungs, in the liquid form it causes cutaneous maceration and is rapidly absorbed through the skin. In the organism it is primarily metabolized to N-monomethylformamide, to a lesser extent to formamide. Urine of individuals exposed to N,N-dimethylformamide was newly found to have higher levels of thioethers, most likely mercapturates, as yet of unknown chemical structure. The correlation between the urinary concentrations of mercapturates (y) and N-monomethylformamide (x) can be expressed by equation y = 4.93 + 0.58 x, with the coefficient of correlation r = 0.90. Part of N,N dimethylformamide metabolites is likely to react with biopolymers, part of it is excreted as metabolic end products, i.e. carbon dioxide, water and urea. Breakdown to mercapturates may implicate N,N-dimethylformamide as being a potential carcinogen. PMID- 4020117 TI - Activity of acid and alkali phosphatase in guinea pigs exposed to the static magnetic fields. AB - The influence of static homogeneous magnetic field on alkali and acid phosphatase in guinea pigs (regarding the twenty four hours rhythm) was studied. The increase of acid phosphatase activity was determined by the time of exposure to magnetic field. No changes in alkali phosphatase activity were observed. PMID- 4020118 TI - Antagonistic activities of coagulase-positive staphylococci. AB - Antagonistic activities were investigated by Frederioq's plate method in 1,014 coagulase-positive staphylococcal strains of different species and origins. Staphylococcin effect was demonstrated in 12 (2%) of the 559 Staphylococcus aureus strains, in 51 (18%) of the 283 S. intermedius strains, and in 1 (3%) of the 36 S. hyicus subsp. chromogenes strains. Lysostaphin was identified in the 15 (5%) S. intermedius strains. In addition, heat-stable bacteriostatic agent was detected in 45 (33%) and heat-labile bacteriolytic agent in 7 (5%) of the 136 S. hyicus subsp. hyicus strains. An attempt was made at antagonistic activity typing in all of the active staphylococcal strains. PMID- 4020119 TI - Cytogenetic analysis of peripheral blood lymphocytes of workers occupationally exposed to styrene. AB - The genetic risk run by workers occupationally exposed to styrene vapors was assessed in two different plants A and B, using the cytogenetic analysis of peripheral blood lymphocytes. In plant A engaged in the manufacture of polystyrene vessels the mean styrene exposure level was found to range between 70 and 150 mg . m-3, in plant B manufacturing sports boats, plastic slides for children and plastic guard-stones it reached the level of about 200 mg . m-3. The rate of aberrant cells (AB.C.) found in plant A workers (N = 36) at the time of first sampling was 1.38% and the value of break/cell (B/C) ratio was 0.015; at the second sampling the rate of AB.C. was 1.41% and the B/C ratio was 0.014. The group of matched controls (N = 19) was found to have 1.26% of AB.C. and 0.014 breaks per cell. Plant B workers (N = 22) exhibited at the first sampling 1.72% of AB.C. and their value of B/C ratio was 0.018, the group of matched controls (N = 22) had 1.36% of AB.C and the B/C ratio 0.015; the respective values at the time of second sampling were 2.81% for AB.C. rate and 0.029 for B/C ratio in the exposed and 1.89% for AB.C. rate and 0.021 for B/C ratio in the control group. It is concluded that styrene exposure levels below 100 mg . m-3 do not pose any serious genetic risk for the exposed population groups. The variations found in the degree of chromosome injury by smoking habits, drug intake pattern, or sex were not statistically significant. PMID- 4020120 TI - Determination of some immunologic parameters in capillary blood samples. AB - A technique for the collection of capillary blood samples and their subsequent analysis is described. The procedure is especially intended for use in children, stomatologic patients and individuals under load test who are to be screened for the level of immunoglobulins. The applicability of this method was verified in a group of 71 patients treated for various chronic liver lesions at the Research Institute of Balneology. The aim was to avoid the distress of repeated venous blood samplings to patients who had to be examined for the dynamic of changes in their immunologic parameters. Totally, nine immunologic parameters were simultaneously determined in the capillary and venous blood of these patients. As confirmed by statistical processing of the data (t-test, F-test, correlation coefficients and regression line equations were calculated) both methods proved equally suitable in terms of the results yielded so that either of them can be safely used for routine human serum analyses. However, the use of the capillary blood technique turned out to cause less discomfort to the patients, and appears to be distinctly of advantage in children and stomatologic patients as well as in repeated blood samplings during load tests and examinations in animal experiments. PMID- 4020122 TI - Renal response to acute volume overload in conscious rats with atrial appendectomy. AB - The presence of volume receptors and a potent natriuretic factor (ANF) in mammalian cardiac atria strongly suggests a central role of the atria in extracellular fluid volume regulation. ANF is stored within granules in atrial appendages, and their removal could alter the response to volume overload. We tested this hypothesis in conscious Wistar rats two weeks after sham operative or atrial appendectomy. The results indicate that removal of the atrial appendages significantly reduced their urinary excretion of water, sodium and potassium during the first hour following acute volume overload. It is concluded that atrial appendectomy alters the ability of rats to handle acute volume overload possibly through a reduction in the ANF available for release. PMID- 4020121 TI - Blood pressure response to antihypertensive therapy: ambulatory versus office blood pressure readings. AB - Blood pressure readings obtained by the physician in his office and ambulatory blood pressures recorded with the semi-automatic Remler device, were compared during a controlled antihypertensive drug trial. Either timolol or methyldopa was administered in in double-blind fashion to 30 patients with uncomplicated essential hypertension. All exhibited a diastolic office blood pressure greater than 95 mmHg at the end of a four-week placebo period. All patients then received a combination of hydrochlorothiazide (25 mg/day) and amiloride (2.5 mg/day). After four weeks of diuretic therapy, timolol (10 mg/day, n = 14) or methyldopa (250 mg/day, n = 16) were added randomly for six weeks. The dose of all antihypertensive agents was doubled after two weeks of therapy with diuretics combined with timolol (n = 7) or methyldopa (n = 16) because of the persistence of diastolic blood pressure levels greater than 90 mmHg at the office. When assessed in the office, the antihypertensive effect of timolol and methyldopa was similar. During ambulatory blood pressure monitoring, however, pressure levels were lower in the patients given timolol (P less than 0.05 for the diastolic). With both regimens, the blood pressure response measured outside the clinic during usual daily activities could not be predicted from that observed with office blood pressure readings. Furthermore the magnitude of the drug induced blood pressure decrease was more reproducible in time when determined outside the clinic. These data suggest that ambulatory blood pressure monitoring is more precise in evaluating the efficacy of antihypertensive therapy than office blood pressure measurement. PMID- 4020123 TI - Characterization of angiotensin I, II, and III from mouse as position-5 isoleucine [Ile5] angiotensins. An HPLC Study. AB - Angiotensin I was generated in vitro in mouse plasma by addition of mouse submaxillary renin. After deproteinization on Dowex 50W-X2 ion exchange resin, the samples were separated by reverse phase liquid chromatography and the fractions analysed by radio-immunoassay for angiotensin I. Angiotensin I from mouse was injected into the jugular vein of a nephrectomized rat in order to generate angiotensin II and III of mouse origin. Carotid arterial blood was collected immediately, centrifuged and the plasma deproteinized and separated on high pressure liquid chromatography (HPLC). The fractions were analysed for angiotensin I, II and III by radioimmunoassays. Retention times for mouse angiotensins in the liquid chromatography system were compared to synthetic [Val5] and [Ile5] angiotensin I, II and III. All three mouse angiotensins coincided with the corresponding synthetic [Ile5] angiotensins during elution, suggesting the same type of angiotensin in mouse and man. An additional study on rat angiotensins confirmed previous findings by other investigators, indicating that the angiotensins of this animal were also of the [Ile5] type. PMID- 4020124 TI - Predictors of cardiovascular morbidity in treated hypertension: results from the primary preventive trial in Goteborg, Sweden. AB - Prognostic factors for cardiovascular disease (CVD) were studied in treated, middle-aged male hypertensives, derived from a random population sample and followed for more than 10 years. In multivariate analysis diastolic blood pressure, smoking, serum cholesterol, proteinuria, angina pectoris and previous stroke were found to be independent predictors of CVD morbidity (non-fatal myocardial infarction (MI), non-fatal stroke, or CVD death). Multivariate analyses for coronary heart disease (CHD), stroke and CVD mortality were also performed and the results are given. Life-table analyses showed a three times higher CVD incidence among smokers than amongst non-smokers and a doubled incidence for subjects with a serum cholesterol in the highest quartile, i.e. above 7.3 mmol/l, compared with those with levels below, and a three times higher incidence for subjects with proteinuria than those without. Non-smokers with a serum cholesterol below 7.3 mmol/l and free of any hypertensive organ manifestation at entry did not differ significantly in CVD morbidity from a normotensive comparison group that was derived from the same population sample. These findings in a well-defined population sample show that in spite of treatment for hypertension the CVD risk is still substantial if organ damage or other risk factors are present. These findings underline the importance of multiple risk intervention. PMID- 4020125 TI - Mononuclear leucocyte intracellular free calcium--does it correlate with blood pressure? AB - Abnormalities of calcium binding and calcium transport in cells from hypertensive subjects or animals have been previously described. Total cell sodium is reported to be increased in white blood cells from hypertensive subjects; thus by analogy with Blaustein's proposal for the vascular smooth muscle cell, mononuclear leucocyte cytosolic calcium might be increased via a reduction of the Na-Ca exchange. Using the fluorescent calcium indicator, quin 2, cytosolic calcium was measured in mononuclear leucocytes from 22 hypertensive and 19 normotensive subjects. There was no significant difference between the mononuclear leucocyte cytosolic calcium level in the two groups. Incubation of the cells with 10(-4) M ouabain reduced 86 rubidium (86Rb) uptake by 80% of the control value but failed to alter cytosolic calcium. These findings are consistent with a minimal role of the Na-Ca exchange in the mononuclear leucocyte and may explain why the cytosolic calcium was not increased in hypertension despite the previous reports of increased total cell sodium in white blood cells. PMID- 4020126 TI - Body composition and its relation to systemic haemodynamics, fluid volume partitions and energy utilization in rats with bilateral ventromedial hypothalamic lesions. AB - Body composition and its relationship with intra-arterial pressure, fluid volume partitions and oxygen consumption were studied in male rats four months following ventromedial hypothalamic (VMH) destruction during the static phase of the development of obesity. Compared with sham-operated controls, rats with VMH lesions had a greater body weight which was related to an increased body lipid content and an elevated arterial pressure and total peripheral resistance. Fluid volume distribution was normal and total body oxygen consumption (per unit of body weight) was reduced. Bilateral destruction of the ventromedial hypothalamus was confirmed in each of the rats studied and no relationship could be demonstrated between the lesion size and the magnitude of haemodynamic changes. It is concluded that the increased arterial pressure observed in obese VMH lesioned rats was directly related to an elevated total body lipid content. PMID- 4020127 TI - The second Sir George Pickering memorial lecture. What regulates whole body autoregulation? Clinical observations. AB - The autoregulation theory of essential hypertension states that the characteristic haemodynamic derangement of this disease, i.e. increased vascular resistance, is a homeostatic response to abnormal sodium retention by the kidneys. The postulated relationship between arterial pressure and urinary sodium excretion is disturbed in such a way that a higher than normal pressure is required for sodium excretion to keep up with intake. This will initially expand plasma volume and raise cardiac output. However, hyperperfusion of the tissues will ultimately induce vasoconstriction, presumably by greater than normal wash out of vasodilator metabolic products. Thus, cardiac output will be restored. Some elements of this theory are not supported by current evidence, but the key element, i.e. the assumption that increased vascular resistance is somehow dependent on abnormal renal sodium handling, is consistent with the following clinical observations: Arterial pressure and urinary sodium excretion are directly correlated over a wide range of pressures in patients with autonomic failure, both acutely during titling and chronically with changes in posture during a 24-h period. The failure to demonstrate pressure-natriuresis in normal subjects may therefore be related to the amplifying effect of the sympathetic nervous system on this mechanism, so that small changes in pressure are capable of inducing large changes in sodium excretion. The pressure-natriuresis curve in patients with autonomic failure is shifted to higher pressures by administration of aldosterone, which is consistent with an important role of renal sodium retention in mineralocorticoid hypertension. Measurements of total extracellular fluid volume, plasma volume/interstitial fluid volume ratio, transcapillary escape rate of serum albumin, cardiac output and arterial pressure at timed intervals during the development of hypertension, in patients exposed to mineralocorticoid excess, or during the reversal of hypertension in nephrectomized patients treated with ultrafiltration haemodialysis, revealed an association of increased total peripheral resistance with a reduced plasma volume/interstitial fluid volume ratio and an increased transcapillary escape rate of serum albumin. This association has also been observed in cross-sectional studies of patients with essential hypertension and suggests that part of the increase in resistance is located at a post-capillary level. It may be related to compression of collapsible venules and veins due to abnormally increased interstitial fluid pressure, not only in sodium-dependent secondary forms of hypertension but also in essential hypertension.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 4020128 TI - Respiratory and cardiovascular responses to hyperoxia, hypoxia and hypercapnia in the renal hypertensive rabbit: role of carotid body chemoreceptors. AB - We tested the hypothesis that in renal hypertension the increased peripheral vascular resistance of neurogenic origin might be due to a reflex through resetting of the carotid body chemoreceptors. The reflex respiratory and cardiovascular functions of the carotid bodies were studied in a one-kidney wrapped hypertension model in conscious rabbits, and compared with a control group of animals, by breathing 100% oxygen, three hypoxic gas mixtures to which were added sufficient CO2 to maintain the PaCO2 constant, and 2 and 4% CO2 in 21% O2 and N2. In the control state (breathing room air) the renal hypertensive animals had a slightly higher respiratory minute volume, a higher level of arterial blood pressure and increased calculated systemic vascular resistance, compared with the normal group, but there was no difference in cardiac output. Hyperoxia had no consistent effect on respiration, heart rate or arterial blood pressure. Increasing degrees of isocapnic hypoxia caused the same degree of hyperventilation and bradycardia in both groups of animals. The arterial blood pressure did not change in either group but there was a transient increase in systemic vascular resistance in the renal hypertensives breathing 9 and 7.5% O2. The respiratory responses to 2 and 4% CO2 were similar in the two groups of animals. In the renal hypertensive animals, serial sections of the carotid bodies showed pathological changes, including subendothelial proliferation in vessels supplying the carotid bodies with narrowing of their lumens, fragmentation of the elastic laminae of the media, hypertrophy of the smooth muscle and extensive fibrosis with occasional haemorrhages. The capillaries, however, were normal. The rostral-caudal lengths of the carotid bodies were similar in the two groups. In view of our findings we conclude that the relatively normal carotid chemoreceptor responses in renal hypertensive rabbits may, in part at least, be the result of the carotid body blood flow through the partially occluded vessels being maintained at near normal levels by the elevated blood pressure. PMID- 4020129 TI - Blood pressure measurement in the elderly: correlation of arterial stiffness with difference between intra-arterial and cuff pressures. AB - Intra-arterial (radial) blood pressure (BP) measurement was compared with the indirect cuff method in 55 healthy volunteers aged from 59-80 years (mean 68.6 +/ 5.2 s.d.). On average, the cuff method underestimated systolic BP by 5 mmHg and overestimated diastolic BP by 8 mmHg. Cuff measurement underestimated systolic BP by greater than 10 mmHg in 17 cases, and by greater than 20 mmHg in three cases. The cuff method overestimated diastolic BP by greater than 10 mmHg in nine cases (one greater than 20 mmHg) and in two cases the cuff overestimated diastolic BP by greater than 30 mmHg, compared with intra-arterial pressures. The differences correlated with pulse wave velocity, an index of arterial stiffness. A pulse wave velocity index reflecting the entire length from the aortic root to the posterior tibial artery (PWVI/ao-pt) gave a correlation (r) of 0.48 (P less than 0.0005) with systolic arterial/cuff (A/C) difference, a correlation of 0.43 (P less than 0.001) with diastolic A/C difference, and a correlation of 0.57 (P less than 0.00001) with the A/C difference in measurement of mean arterial pressure. A positive but weaker correlation was observed between A/C difference and PWVI aorta-femoral. Although the pressure differences were not as great in these healthy elderly subjects as in previous studies of patients suspected of having pseudo-hypertension, caution still appears to be indicated in the interpretation of cuff blood pressure measurement in the elderly. PMID- 4020130 TI - The measurement of central noradrenergic activity in spontaneously hypertensive rats: a comparison of free 3,4-dihydroxyphenylethyleneglycol levels with FLA-63 induced noradrenaline depletion. AB - Noradrenergic activity was measured in the brainstem, hypothalamus and thoracic spinal cord of male and female spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) rats at 6 and 28-36 weeks of age. Two techniques were used, measurement of a major noradrenaline (NA) metabolite, free 3,4-dihydroxyphenylethyleneglycol (DHPG), and measurement of the rate of decline in brain NA levels following dopamine-beta-hydroxylase (DBH) inhibition by FLA-63. There was a good correlation between the changes with age in NA turnover measured by the two techniques. NA levels and NA turnover measured by both techniques fell with age in brainstem and thoracic spinal cord in both SHR and WKY rats. In both strains these falls in turnover were associated with increases in blood pressure. However, the increase in blood pressure in the SHR was greater than in the WKY, even though NA turnover fell to a similar extent in both strains. These data show a difference in the pattern of change in NA levels and turnover in the brainstem and thoracic spinal cord compared to other brain regions and may therefore be related to the development of higher levels of blood pressure in older rats in both strains. They do not offer a simple explanation for the much higher blood pressures seen at all ages in the SHR. PMID- 4020131 TI - Characteristic changes of plasma proteins in the Dahl hypertensive rat strain (DS) during the development of hypertension. AB - Several recent studies have reported the existence of additional plasma proteins in essential hypertensive patients and strains of genetically hypertensive rats. The aim of this work was to look for similar changes in a model of salt induced hypertension, the Dahl salt sensitive (DS) rat, using the sodium dodecyl sulphate (SDS) polyacrylamide gel electrophoresis. No additional proteins were found when different staining techniques were employed (Coomassie, silver). However, during the development of hypertension a characteristic change in the plasma protein pattern of DS rats occurred, which could not be detected in the majority of normotensive control animals. Treatment with nifedipine inhibited both the development of hypertension and this specific change in the plasma proteins, in spite of continuous dietary salt loading. It is postulated that the plasma protein changes reflect a regulatory phenomenon of hypertension. PMID- 4020132 TI - Long-term efficacy of screening for hypertension in a community. AB - Screening for hypertension in the community leads to the identification of hypertensive people not previously detected, and those detected but inadequately treated or not treated at all. The aim of the present study was to assess the long-term efficacy of screening for blood pressure control in a general population. During 1981, 2139 parents of high school students were invited to our institute for a blood pressure measurement; 1533 persons (71.7%) attended the screening; 239 of them (15.6%) were found to be hypertensive (diastolic blood pressure greater than or equal to 95 mmHg or already receiving antihypertensive treatment). Among the hypertensives, 42.3% did not know that they had high blood pressure, and only 7.5% had their blood pressure controlled by treatment. After being informed about the importance of lowering their blood pressure levels, all hypertensives were invited again to the institute for a further evaluation. Two hundred and two persons (84.5%) attended the re-examination. Of these, 154 (76.2%) were still hypertensive. Of the 202, 151 (74.7%) had contacted their physicians. The most common advice was to make further measurements of blood pressure over a period of time, followed by laboratory tests. The proportion of treated hypertensives rose from the initial 33.1% to 53.9%, but in about half the patients normalization of blood pressure was not achieved. Physicians tended to treat only people with moderate to severe hypertension.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4020133 TI - Characterization of circulating and cutaneous IgA immune complexes in patients with dermatitis herpetiformis. AB - Dermatitis herpetiformis (DH) is a chronic, blistering skin disease characterized in part by deposits of IgA at the dermal-epidermal junction. Eighty-five percent of DH patients have granular IgA deposits and have an associated gluten-sensitive enteropathy (GSE). In contrast, 15% of DH patients have a linear pattern of IgA deposits and no associated intestinal abnormality. Although circulating IgA antibodies against skin are not present in these patients, 40% of DH patients do have IgA-containing circulating immune complexes (IgA-CIC). The role and origin of the cutaneous IgA and the IgA-CIC in patients with DH are unknown; however, the association of GSE with the granular IgA deposits suggests that a mucosal immune response may be important in the pathogenesis of DH. We have characterized the IgA subclass composition of the cutaneous IgA deposits in patients with DH, and have isolated and characterized the IgA-CIC from these patients. Twenty-nine of 29 patients with DH and granular IgA deposits were found to have only IgA1 deposits. Ten of 11 patients with linear IgA deposits also had only IgA1 deposits; one of 11 had IgA2 deposits. Isolated IgA-CIC from the sera of eight patients with DH and granular IgA deposits were found to contain both IgA1 (58% +/- 5, mean percent of total IgA +/- SEM) and IgA2 (42% +/- 5), as were IgA-CIC from two patients with ordinary GSE without cutaneous IgA deposits. The IgA subclass composition of the isolated immune complexes was significantly different from the serum IgA1 and IgA2 composition (serum IgA1 = 76% +/- 6; IgA2 = 24% +/- 5, p less than 0.025, Student's t-test), and suggests that the IgA-CIC may arise from gut-associated lymphoid tissue (GALT). Sequential anti-IgA1 absorption of serum which contained IgA-CIC did not remove all the IgA-CIC, suggesting that the complexes circulate as separate IgA1 and IgA2 complexes. The finding of IgA1 alone in the skin of patients with DH suggests that the cutaneous IgA may not arise from GALT, or that IgA1, possibly arising in GALT, is preferentially bound to DH skin. Because IgA-containing CIC which contain both IgA1 and IgA2 were found in the serum of patients with DH and with ordinary GSE, it seems unlikely that IgA-containing CIC are responsible for the cutaneous IgA deposits seen in DH. PMID- 4020134 TI - Immune response to nucleic acid antigens and native DNA by human peripheral blood lymphocytes in vitro. AB - The immunogenicity of DNA fragments (either oligonucleotide (oligo) or total DNA digest) covalently linked to keyhole limpet hemocyanin (oligo-KLH or DNA-KLH) was tested with peripheral blood lymphocytes (PBL) from 63 systemic lupus erythematosus patients (SLE) in vitro. PBL from 10 normal individuals and 11 rheumatoid arthritis (RA) patients served as controls. Antibodies to three nucleic acid antigens (oligo, denatured DNA (d-DNA), and native DNA (n-DNA] were assayed in supernatants of cultured lymphoid cells by a sensitive solid-phase radioimmunoassay. More than 50% of SLE and RA patient lymphoid cells formed spontaneous antibodies to one or several nucleic acid antigens. In contrast, only two normals did. After in vitro challenge with oligo-KLH or DNA-KLH, cultured lymphocytes of more than 50% of SLE patients formed antibodies to one or several nucleic acid antigens. Similar results were obtained in PBL from RA patients. In SLE patients, the response to both antigens was either monospecific or polyspecific, but DNA-KLH appeared to raise a greater proportion of antibody to n DNA than oligo-KLH. A greater proportion of patients with active disease responded in vitro compared with those with inactive disease. A mixture of oligo together with KLH was not immunogenic in vitro. Oligo-KLH or DNA-KLH did not raise antibody to an irrelevant antigen, ovalbumin. Of particular interest, PBL from seven of 10 normal subjects formed antibody to n-DNA after challenge in vitro with oligo-KLH. The data support the view that DNA fragments could be an important immunogen in SLE. Furthermore, this study provides an in vitro model to test the tolerogenicity of similar fragments of DNA linked to self carrier molecules such as gamma-globulin. PMID- 4020135 TI - Longitudinal assessment of immunologic abnormalities of mice with the autosomal recessive mutation, "wasted". AB - Mice homozygous for the autosomal recessive mutation wasted (wst/wst) undergo a progressive wasting beginning at the third week of postnatal life, when body weight declines in the mutants. The wst/wst mice do not survive past 30 days of age. The present report describes histologic and functional abnormalities in a longitudinal analysis (17 to 29 days postpartum) of wst/wst mice. In addition to a marked age-dependent decline in wst/wst body weight as well as spleen and thymus wet weight to body weight ratios, we have observed a significant decline in spleen and thymus cell number in these organs, compared with phenotypically normal (+/+ or +/wst) littermates. Histologic analysis of the wst/wst thymus revealed marked cortical pyknosis at 23 days of age and significant cortical depletion by 26 days postpartum. The wst/wst spleen at 23 days of age and later was characterized by a marked reduction in the content of red pulp. Lymphoproliferative responsiveness to Con A was markedly altered in the wst/wst thymus and spleen, in an age-dependent fashion, compared with normal littermates. The wst/wst spleen LPS responsiveness was also markedly altered in an age dependent fashion. Hypotheses are presented concerning the possible site(s) of gene action in the wst/wst mutant which may mediate the observed morphologic and functional abnormalities. PMID- 4020136 TI - Phagocytosis by mouse peritoneal macrophages plated on monoclonal antibody-coated immune complex-substrates: effects of complexes of different IgG subclasses on Fc receptor functions. AB - Macrophages plated on immune complex-coated substrates of different mouse IgG subclasses were examined for their capacities to phagocytose sheep red blood cells (SRBC) coated with monoclonal antibodies (MAb) of various IgG subclasses. IgG2a-and IgG2b-coated substrates abrogated macrophage phagocytosis of particles coated with any of the four mouse IgG subclasses. These results were confirmed by the use of two MAb of each of the IgG2a and IgG2b subclasses, with one of the MAb specific for dinitrophenyl groups and the others for SRBC. IgG3-coated substrates reduced the macrophage uptake of IgG2a-but not IgG2b-coated particles. Rabbit IgG coated substrates ablated the uptake of SRBC coated with all mouse IgG subclasses. Resident and thioglycollate-elicited macrophages showed similar phagocytosis reduction when plated on these immune complexes. The phagocytosis of complement-coated particles was not affected by these IgG-coated substrates. Macrophages plated on both IgG2a-and IgG2b-coated substrates showed reduced immunofluorescence staining by an anti-IgG2b Fc receptor (FcR) Ab, 2.4G2 and reduced E(IgG2a) and E(IgG2b) binding. The results show that substrates coated with various IgG subclasses can abrogate phagocytosis mediated by FcR that do not have binding specificity for the substrate-immobilized Fc ligand, and suggest that the three classes of mouse FcR co-modulate. PMID- 4020137 TI - Disease-associated loss of erythrocyte complement receptors (CR1, C3b receptors) in patients with systemic lupus erythematosus and other diseases involving autoantibodies and/or complement activation. AB - Although surface membrane density of complement receptor type one (CR1) on erythrocytes (E) is probably an inherited trait among normal individuals, recent evidence from our laboratories suggests that the reduced number of CR1 per E observed in patients with systemic lupus erythematosus (SLE) results from acquired as well as genetic factors. In the present investigation, the number of CR1 per E was quantitated with 125I-monoclonal anti-CR1 and was found to vary inversely with disease activity in patients with SLE who were followed serially for as long as 14 mo. Although evidence for E surface-bound immune complexes or fixed C3b/iC3b was not obtained, periods of disease activity and low amounts of CR1 per E correlated with the presence of 100 to 800 molecules per E of fixed C3dg fragments (less than 100 C3dg per E in normal subjects). Reduced CR1 and excess fixed C3dg on E also were observed in patients with other disorders associated with complement activation, including chronic cold agglutinin disease, autoimmune hemolytic anemia, paroxysmal nocturnal hemoglobinuria (PNH), Sjogren's syndrome, and mycoplasma pneumonia. A significant negative correlation (r = 0.498) between CR1/E and fixed C3dg/E was demonstrable in 255 individual assays evaluated by regression analysis. CR1 decreased and fixed C3dg increased during active disease; the converse was obtained during remission. In patients with active SLE, both serum complement activity and E CR1 decreased, whereas fixed C3dg fragments increased. By piecewise linear regression analysis, the appearance of 100 to 400 C3dg molecules on patients' E corresponded to a 27 to 60%, reduction in the number of CR1 per E (p less than 0.0002), confirming that fixation of C3 to E was correlated with a loss of CR1. In patients with PNH, low values for CR1 were observed on moderately complement-sensitive PNH type II E in association with increased fixed C3 fragments; however, the markedly complement sensitive PNH type III E had essentially normal amounts of CR1 and bore little fixed C3. The addition of soluble DNA/anti-DNA immune complexes to normal blood generated levels of fixed C3dg fragments on E comparable to those observed on E from patients with SLE. Kinetic experiments indicated that C3b was fixed to E during the process of immune complex binding and release from E CR1, and that this fixed C3b was subsequently degraded rapidly to fixed iC3b and more slowly to fixed C3dg without the loss of CR1 that occurs in vivo.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 4020138 TI - Immune oxidative injury induced in mice exposed to normobaric O2: effects of thiol compounds on the splenic cell sulfhydryl content and Con A proliferative response. AB - In vivo exposure of mice to normobaric O2 depresses the cellular immune response by a mechanism that remains unknown. In vitro oxidative injury leads to decreased sulfhydryl groups (SH) in lymphocytes. To determine whether in vivo exposure to O2 would have similar effects, we measured the SH content in spleen cells both from mice that had been exposed to normobaric O2 (O2 SC) and from controls exposed to ambient air (Air SC). The SH content of the fresh O2 SC was slightly decreased, whereas after 48 hr of culture, the SH content and the proliferative response of these cells were found to vary with the type and concentration of thiol or disulfide compounds added to the culture medium. Under standard culture conditions, i.e., RPMI 1640 medium containing 0.41 mM half-cystine, the SH content in O2 SC decreased sharply to about 10 and 20% that of Air SC in the absence or presence of Con A (2 micrograms/ml), respectively. Under these culture conditions, the proliferative response of O2 SC was 20.5% +/- 3.2 of Air SC. In cystine-free RPMI 1640 medium supplemented with various concentrations of L cystine, L-cystine and 2-mercaptoethanol (2-ME), L-cysteine, or reduced glutathione (GSH), the proliferative response to Con A and the SH content of the O2 SC varied in parallel and were correlated (p less than 0.01). Half-cystine (0.41 mM) plus 2-ME (5 X 10(-5) M) or L-cysteine alone (4 mM) completely protected the SH content of O2 SC and induced a proliferative response 82% +/- 6 that of the controls. In cystine-free RPMI 1640 medium supplemented with GSH (4 mM), the SH content and proliferative response of O2 SC were 79 and 67.5% of Air SC, respectively. Other concentrations of these compounds were less effective. Oxygen scavengers such as SOD, catalase, mannitol, and vitamin E did not protect against the decrease of the O2 SC. The induced oxidative cellular damage might be related in part to a membrane lipid peroxidative process. These data show that in vivo exposure of mice to normobaric O2 induced lesions in splenic cells manifested under standard culture conditions by a decrease in both SH content and Con A proliferative response. The extent of these alterations could be modulated by variations of the thiol environment. Protection of the SH content correlated with protection of the proliferative response of the O2 SC. PMID- 4020139 TI - Characterization of a C5a receptor on human polymorphonuclear leukocytes (PMN). AB - Elucidation of the interactions between C5a and granulocytes is central to understanding the role of C5a in inflammation. In this study, interactions between C5a and PMN have been studied at two levels. Binding of human C5a to intact human cells has been characterized by using the radiolabeled ligand 125I C5a. Binding is shown to be reversible, saturable, and to reach equilibrium in 60 to 90 min at 0 degrees C. Results show high affinity C5a binding sites with Kd = 2 X 10(-9) M and a range of 50,000 to 113,000 binding sites per PMN. These values for C5a receptors are comparable with the number of fMLP and LTB4 receptors on PMN. Binding of C5a to PMN fails to reach equilibrium at 37 degrees C because there is an irreversible loss of available surface receptors caused by an active internalization of the ligand-receptor complex. Interactions between C5a and human PMN were characterized further by cross-linking experiments, with the use of ethylene glycol bis succinimidylsuccinate (EGS). Cross-linking of 125I-C5a to intact PMN followed by subcellular fractionation revealed a single radioactive band present only in the plasma membrane fraction and visualized by autoradiography. Similar experiments resulted in a covalent linkage between 125I C5a and a component in the isolated plasma membrane of PMN. The covalent complex containing C5a and a putative receptor has been visualized by autoradiography as a single 60,000 Mr complex on SDS-PAGE. The complex is not present when experiments are performed in the presence of excess unlabeled C5a or in the absence of EGS. Therefore, the putative receptor for C5a on human neutrophils is estimated to be approximately 48,000 Mr, assuming contribution of 12,000 to 13,000 daltons by the ligand 125I-C5a. PMID- 4020140 TI - Prophylactic immunization against experimental leishmaniasis. IV. Subcutaneous immunization prevents the induction of protective immunity against fatal Leishmania major infection. AB - Durable immunity against fatal L. major infection in genetically susceptible mice can be induced by immunization with 150,000-rad irradiated or heat-killed promastigotes administered i.v. or to a lesser extent i.p. Conversely, subcutaneous (s.c.) and intramuscular (i.m.) injections are not only totally ineffective but generally increase susceptibility to and enhance the progression of the disease, leading to earlier mortality. This detrimental effect is particularly evident with lower infecting challenge doses. Disease exacerbation is apparent in mice given 4 X s.c. injections of as few as 2 X 10(4) irradiated promastigotes, but it appears most potent after doses of 2 X 10(7). When mice given 4 X s.c. injections were subsequently immunized i.v. with 2 X 10(7) irradiated promastigotes, they failed to develop any evidence of protection against infection with 2 X 10(5) promastigotes, whereas mice given i.v. immunization alone were strongly protected. Thus, s.c. injections are capable of blocking the prophylactic effect of i.v. immunization with irradiated parasites. This inhibitory effect can be achieved with a single s.c. injection, although rather less potently than with four, and is even effective against four repeated weekly i.v. immunizations. Once induced, the effect persists undiminished after 100 days. A weaker effect is also inducible by s.c. injection given after i.v. immunization. The blocking effect of s.c. injection is not dependent on continuing viability of the promastigotes, as it can be induced equally readily with heat-killed, formalin-fixed, or sonicated parasites. The phenomenon extends to mouse strains genetically resistant as well as susceptible to L. major infection and, in congenic mice of BALB background, is independent of the major histocompatibility (H-2) gene complex. PMID- 4020141 TI - Schistosoma mansoni: detection by monoclonal antibody of a 22,000-dalton surface membrane antigen which may be blocked by host molecules on lung stage parasites. AB - Monoclonal antibody M.2 binds to the surface membranes of cercariae and developing schistosomula. This antibody was generated from mice immunized with membrane-enriched extracts of mechanically transformed schistosomula. The antigen detected by M.2 was shown to persist on developing schistosomula for at least 96 hr post-transformation. M.2 also bound to the surface of living, cultured lung worms but not to freshly harvested lung worms. The ability of M.2 to bind to cultured lung worms coincided with the loss of host H-2 from the parasite surface. The apparent m.w. of the antigen was 22,000; an antigen with the same apparent m.w. was immunoprecipitated from cercariae, schistosomula, lung worms, and adult worms. PMID- 4020142 TI - Immune responses during human Schistosomiasis mansoni. XI. Immunologic status of patients with acute infections and after treatment. AB - Sixteen patients, 8 to 30 yr of age, with acute (toxemic) phase schistosomiasis mansoni were studied immunologically within 2 to 3 mo of their exposure to Schistosoma mansoni cercariae, and were monitored after chemotherapy. Total leukocyte levels and peripheral blood eosinophilias were higher in these patients than in similar individuals with chronic schistosomiasis mansoni. In contrast to chronic patients, the eosinophilias of the acute cases were decreased rather than elevated upon treatment. Total lymphocyte population (T and B cell) percentages were not altered during acute infection. Lymphoid subset (T3+, T4+, and T8+) analysis revealed elevated levels of both T4+ and T8+ cells. In vitro blastogenic responses of peripheral blood mononuclear cells (PBMN) to heterogeneous schistosome-derived antigens (eggs, SEA; adult worms, AW; and cercariae, CERC) were evaluated. SEA responsiveness was considerably higher than that of patients with chronic S. mansoni infections. The ratios of SEA to AW responses in acute cases gave a mean of 2.0, as opposed to 0.5 for a comparable group of chronically infected patients. The sera of most acute patients already contained suppressive factors that specifically decreased schistosomal antigen-induced PBMN blastogenesis. Chemotherapy of acute cases lead to a diminution of PBMN responsiveness to SEA and CERC. Treatment of patients with chronic infections lead to the elevation of such responses. PBMN from patients with acute infections produced lymphokine leukocyte inhibition factor upon exposure of the cells to SEA but not AW. A similar pattern was true for production of the lymphokine activity mitogenic factor. Levels of antibody in sera of acutely infected patients against SEA, CERC, and AW were considerably higher than levels in sera of chronically infected patients matched for age and intensity of their infections. These high antibody titers persisted for at least 6 mo after treatment, and were unrelated to the intensity of infection. The immunologic status of these patients with acute schistosomiasis mansoni differed considerably from patients with chronic infections. These findings re-emphasize the immunoregulatory events that apparently develop upon continued exposure to schistosomes and their products during chronic infection. PMID- 4020143 TI - Studies on microcapsules to replace erythrocytes in the passive agglutination reaction. AB - Two kinds of microcapsules were made from polyurethane and polyurea. Each capsule had a mean diameter of 6 microns, a specific gravity of 1.10, and was red in color. The capsules were coated with ovalbumin condensed with glutaraldehyde. The coated capsules were agglutinated with anti-ovalbumin antibody. The polyurethane capsule (positive charge) bound more ovalbumin and showed a higher sensitivity than did the polyurea capsule (negative charge) or erythrocytes. PMID- 4020144 TI - A new method of iodinating ovalbumin, a protein which lacks accessible tyrosine groups, by conjugation to a highly fluorescent coumarin active ester, CASE. AB - A simple and efficient method is described to overcome the difficulty in radiolabelling ovalbumin and is applicable to any protein. Coumarin-3-acetic acid N-OH-succinimidyl ester (CASE) binds directly to ovalbumin in aqueous solution to form covalent bonds with free amino groups. The attached CASE residues can then be radiolabelled by the chloramine-T method. This offers an inexpensive alternative to the Bolton and Hunter reagent with the advantage that CASE is fluorescent. This property, apart from direct use as a fluorescent tag, allows one to monitor the conjugate before radiolabelling. Below a conjugation ratio of 9:1, CASE-ovalbumin retained full antigenic identity with ovalbumin. PMID- 4020145 TI - A novel method for the detection of variation in solid-phase immobilised antibody concentration and its possible application in quality control in immunoassay. AB - Variation of solid-phase antibody concentration could give rise to poor intra- and interassay precision. A new method to detect this variation is reported. Pooled sera with thyroxine (T4) values at the low, medium, and high ranges were assayed in duplicate using anti-T4-coated polystyrene beads. The antigen-antibody complexes were dissociated with methanol-water mixture and the antibodies re-used for subsequent T4 assays in which the same beads were used with the same set of standards and pooled sera. A second set of assays using randomised beads after each assay-wash cycle were also carried out. The variations in weights and surface structures of the beads were also studied. The variation of T4 results of group methods using polyethylene glycol in an external quality control program was also compared with that of covalently linked solid-phase particulate antibody methods over 2 periods. The experimental results showed that there was bead-to bead variation of antibody concentration which could give rise to poor precision. Rigorous control of the immobilised antibody concentration could further improve the assay performance. PMID- 4020146 TI - Preparation of monoclonal antibody to sulfatoxygalactosylglycerolipid by in vitro immunization with a glycolipid-glass conjugate. AB - A monoclonal antibody to the testicular sulfatoxygalactosylglycerolipid has been raised following in vitro stimulation of lymphocytes with glycolipid immobilized on glass beads by means of a photoactivatable heterobifunctional crosslinking agent. The antibody can distinguish between glycerol and sphingosine-based sulfoglycolipids. PMID- 4020147 TI - Specific immunoglobulin production and enhanced tumorigenicity following ascites growth of human hybridomas. AB - Human X human hybridomas constructed with the B6 lymphoblastoid clone, which produces antitetanus toxoid (TT) antibody, and the lymphoblastoid cell line KR-4 or human hybrid myeloma KR-12, were adapted to growth as ascites in pristane treated BALB/c nude mice by a single prior passage as a solid subcutaneous (s.c.) tumor in irradiated nude mice followed by in vitro culture. Both B6 X KR-4 and B6 X KR-12 hybrids produced anti-TT antibody and phenotypically resembled the lymphoblastoid KR-4, or the hybrid myeloma KR-12 parent, respectively. Growth as ascites increased the tumorigenicity of both hybrids in nude mice as measured by tumor incidence and rate of tumor growth. The observed increase in tumorigenicity of these hybrid cells after ascites growth was associated with a substantial loss of chromosomes. Passage of the B6 X KR-4 lymphoblastoid hybrid resulted in several reversible morphological changes characteristic of myeloma cells. These changes correlated with increased human Ig production. These observations provide a system for greatly amplifying human monoclonal antibody production. PMID- 4020148 TI - Detection and enumeration of monocytes in human blood with peanut agglutinin. AB - Binding of peanut agglutinin (PNA) to normal human peripheral blood mononuclear cells was analyzed on a cell sorter, and compared to the binding of the monocyte specific monoclonal antibodies Mac-1 and Leu-M3. Each of the reagents labeled 9 11% of the mononuclear cells and similar binding patterns were observed. Of the PNA+ cells, 67% adhered to plastic petri dishes, whereas 76% of Mac-1+ cells were adherent. No competition for binding was observed between PNA and Mac-1 on the one hand, or PNA and Leu-M3 on the other. In double staining experiments, about 10% of the cells, comprising 80% of the monocytes, were PNA+ Leu-M3+. Our results show that PNA can serve for the identification and enumeration of monocytes in human peripheral blood. PMID- 4020149 TI - Fiber optic probe cytometer. AB - An optical fiber probe is used to both excite and collect fluorescence from a suspension of cells. The configuration of the probe is such that one or a few cells are sensed at a time, with a convenient cell concentration. With fluorescently labeled antibodies to cellular antigens, the fiber optic cytometer is able to identify the presence of a specific set of cells with high sensitivity. PMID- 4020150 TI - A short-duration polyethylene glycol fusion technique for increasing production of monoclonal antibody-secreting hybridomas. AB - In this study the exposure period of the lymphocyte-myeloma cell mixture to the fusogen was evaluated for its influence upon the yield of total hybridoma colonies and those which secreted monoclonal antibodies. Sp2/0 and FOX-NY myeloma cells were fused for varying periods with murine splenic lymphocytes immunized with sheep red blood cells. The optimal fusion period consisted of adding the fusogen (5.0 ml Kodak 1450 PEG, 0.5 ml dimethylsulfoxide, and 4.5 ml of phosphate buffered saline, pH 7.0) to the cell mixture over a 45 s period at 37 degrees C. The fusion process was stopped by gradually diluting the mixture in 50 ml of RPMI 1640. After 10 min, the cells were centrifuged, resuspended in selective medium with feeder macrophages and cultured. In comparison to common, longer fusion techniques, this procedure produces approximately a 5-fold increase in the number of hybrids produced when using the Sp2/0 cells and a 30-fold increase in the number of hybrids produced when using the FOX-NY cells as the fusion partner. In both cases, virtually all the wells contain monoclonal antibody-secreting hybridoma colonies. This high efficiency fusion technique can be used most advantageously to produce monoclonal antibodies against weak immunogens or to reduce the time needed for immunization with stronger immunogens. PMID- 4020151 TI - Neutrophil leucocyte chemotaxis: a simplified assay for measuring polarizing responses to chemotactic factors. AB - A method is described which greatly simplifies the screening of compounds which are potentially chemotactic for neutrophil leucocytes. Neutrophils isolated from blood by a standardised procedure are greater than 95% spherical in morphology. Addition of chemotactic factors in isotropic, non-gradient, concentrations induces the spherical shape to become polarized. The degree of polarity depends on the concentration of the factor used, as does the percentage of cells which become polarised. All compounds which induce a good response in assays measuring cell accumulation or orientation in gradients induced a consistent polarizing response in non-gradient conditions with the cells held in suspension. The advantage of this simplified assay over methods currently in use are discussed. PMID- 4020152 TI - Production and characterization of [14C]protein A, a long-lived immunological reagent. AB - A procedure for the production of [14C]protein A is described which involves reductive methylation of lysine residues with [14C]formaldehyde and NaCNBH3. The binding of [14C]protein A to IgG is apparently unaltered, as determined by competitive binding studies. The use of [14C]protein A may be preferred to that of 125I-protein A when a radioactive label with a long half-life is desirable. PMID- 4020153 TI - Biochemical aspects of immunotoxin preparation. AB - The preparation of immunotoxins, hybrid proteins formed by disulfide bonding an antibody and the A-chain of ricin, has been studied in detail. Optimal conditions, both for the modification of the antibody and the coupling reaction between the modified antibodies and the toxin subunit, have been determined. Conditions of time, temperature and stoichiometry studied suggested 2 protocols for each of the 2 steps of this preparation. Purification and analysis of the physicochemical and biochemical properties of the products yielded well characterized agents, likely to be of value in clinical studies. PMID- 4020154 TI - [The anterior and transperitoneal approach in the surgery of the kidney and ureter]. AB - Because of the variety of situations encountered in surgery of the kidney and ureter, the methods of approach to these organs need to be diversified. In this context, the authors discuss the place of the anterior and transperitoneal approach, based on a series of 573 cases. Its principal indications are: excision of large kidney tumours or pseudo-tumours, conservative treatment of hydronephrosis, removal of pelvic calculi, staged operations or operations on bilateral lesions, re-operations resulting in secondary nephrectomy or repair of the collecting system. The modalities, advantages and disadvantages are discussed and the authors stress the complications which may result from opening of the peritoneum. Overall, the anterior and transperitoneal approach, in the situations in which it is indicated, is an easy and safe operative technique, superior to the usual sub-peritoneal approaches. Its results are very satisfactory; they should overcome reservations which have surrounded this technique for so long and should give it a definite place beside the classical approaches, which nevertheless remain supreme. PMID- 4020155 TI - [Cystine lithiasis in the adult. Apropos of an isolated case without familial antecedents]. AB - We report on a case of cystinuria in an adult woman without any familial or self stone-forming history. The first symptom appeared at 43 years, as an acute renal colic caused by an obstructing ureteral calculous. Hence, this case differs from the majority in its isolated form of presentation and its uncommon age of incidence. Two clinic aspects of cystinuria are emphasized: the precocity of recurrence or stone growth without treatment, and the success obtained frequently in relapses prevention with prophylactic measures (dietary patterns, urine alkalinisation), and continued medical therapy. PMID- 4020156 TI - [Priapism through the centuries]. AB - Priapism is known from egyptian antiquity, but greek doctors give the name of god Priape, to this pathology. The physiopathology is controversial, between Pare and the authors of Middle age tradition medical. The treatment is at first the use of quack medicines, and the Velpeau used surgery. PMID- 4020158 TI - A porphyria cutanea tarda-like distribution pattern of porphyrins in plasma, hemodialysate, hemofiltrate, and urine of patients on chronic hemodialysis. AB - The porphyrin investigations of plasma, dialysate, hemofiltrate, and urine in 50 chronic renal patients without bullae undergoing hemodialysis imply that a hyperporphyria exists. All 50 dialysis patients without blisters had significantly elevated plasma porphyrins with a mean of 27.4 micrograms/liter (SD: 10.0). Normal values were established in 51 nonporphyric ambulatory patients with normal renal function. The mean plasma porphyrin content in this group was 10.6 micrograms/liter (SD: 1.7). Porphyrin values in dialysates of 41 patients with chronic renal failure ranged from 2.6-6.3 micrograms/liter (mean, 3.9 micrograms/liter) and were much lower than the porphyrin content in hemofiltrates of 9 patients which ranged from 10-27 micrograms/liter with a mean of 20 micrograms/liter. In addition, plasma, hemofiltrate, and urine of 5 dialysis patients with blisters and porphyria cutanea tarda (PCT) were investigated. The plasma values were extremely elevated and exceeded those of PCT patients with normal renal function. Whether the dermatologic manifestations of chronic hemodialysis can be interpreted as a "forme fruste" of PCT should be subjected to further investigations. PMID- 4020157 TI - Neoplastic transformation of C3H mouse embryo 10T1/2 cells by 8-methoxypsoralen plus UVA radiation. AB - The effect of 8-methoxypsoralen plus UVA radiation (PUVA) on cell killing and induction of transformation was studied in the C3H mouse embryo 10T1/2 cell line. Dose-response data for both survival and transformation were obtained as a function of 8-methoxypsoralen (8-MOP) concentration and UVA dose. PUVA treatment caused cell death and induced transformation in a dose-dependent manner. Treatment of cells with 8-MOP alone (10 micrograms/ml) or UVA alone (90 J/m2) had no effect on either cell killing or transformation. The product of 8-MOP concentration and UVA dose calculated at 10% survival and 10(-3) transformation frequency levels were quite similar regardless of 8-MOP concentration or UVA dose. This suggests that there exists a simple reciprocal relationship between 8 MOP concentration and UVA dose. Both type II and type III foci induced by PUVA treatment were tumorigenic in vivo. These data provide further evidence for the carcinogenicity of PUVA treatment. In addition, the system described here could serve as a valuable model for studying the relationships between transformation and the specific cellular and molecular lesions induced by PUVA treatment. PMID- 4020159 TI - Appearance of dark keratinocytes following intracutaneous injection of cholera toxin in mouse skin. AB - Intracutaneous injection of cholera toxin (CT), exotoxin of Vibrio cholerae, induces epidermal hyperplasia in mice, rats, and hamsters. In the work reported here we found that, like other hyperplasiogenic compounds such as 12-O tetradecanoylphorbol-13-acetate which are tumor promoters, CT induces dark basal keratinocytes (dark cells) in the epidermis of mice. These are distinct from other epidermal cells since they contain dense cytoplasm rich in ribosomes and tonofilaments. This was demonstrated by electron microscopy and by toluidine blue staining of paraffin- or Epon-embedded sections. They comprised 3.1% of interfollicular basal cells 24-64 h after injection of 1 ng CT as compared with 0.5% in saline-injected skin. It was found by autoradiography of paraffin sections that about 47.2% of dark cells were labeled with [3H]thymidine at these times, while under the same conditions, labeling indices of basal cells were about 30% at the peaks. These results are discussed in relation to tumor promotion in two-stage carcinogenesis of mouse skin. PMID- 4020160 TI - Epidermal cell proliferation in guinea pigs with experimental dermatophytosis. AB - To elucidate the mechanisms underlying the self-healing process of experimental dermatophytosis produced in guinea pigs by an occlusive method with Trichophyton mentagrophytes, epidermal proliferative activity was evaluated by the in vivo tritiated thymidine-labeling technique performed at various intervals after the first and second infections. Determination of labeling indices disclosed that an increased epidermal proliferation correlated well with the severity of inflammatory changes, i.e., a peak activity was noted after 10 days in primary infection and at 2 days in reinfection, respectively, and was followed by subsequent spontaneous lesion clearance after 10 days. Application of a heat killed spore suspension produced inflammatory changes with enhanced epidermopoiesis, similar to those induced by reinoculation of living spores, only in immune animals. The present results indicate that the dermatitic changes occurring in experimental dermatophytosis increase epidermopoiesis which facilitates elimination of the fungus from the stratum corneum and that host immune activity, particularly contact sensitivity to fungal antigen, exerts a crucial role to induce these changes. PMID- 4020162 TI - Regulation of local subcutaneous blood flow in patients with psoriasis and effects of antipsoriatic treatment on subcutaneous blood flow. AB - Local regulation of the doubled subcutaneous blood flow (SBF) rates in psoriatic lesional skin was studied in 8 patients using a traumatic epicutaneous 133Xe labeling washout technique. Venous stasis of 40 mm Hg induced a significant reduction in the SBF (-34%, p less than 0.01), i.e., a normal vasoconstrictor response. Limb elevation of 40 cm above heart level induced no statistical changes in the SBF (p = 0.50), i.e., a normal local autoregulation response. This indicates normal, local regulation mechanisms of SBF in psoriasis. In another 8 patients, the effect on SBF of a 4-week antipsoriatic treatment with tar was studied in lesional and symmetrically nonlesional skin areas. One patient was clear of psoriasis on day 22, and was followed only to that time. The mean pretreatment SBF in lesional skin areas was 3.87 +/- SD 0.78 ml X (100 g X min) 1, which was not statistically different from measurements on days 3, 7, 14, and 21 after treatment had started. Between day 21 and day 28, the SBF decreased significantly to 3.38 +/- SD 0.78 ml X (100 g X min)-1, p less than 0.05. The difference between the pretreatment SBF and SBF at the end of treatment was statistically significant, p less than 0.05. The changes in SBF in symmetrically nonlesional skin areas were statistically nonsignificant during the period of treatment. Pretreatment SBF was 2.60 +/- SD 1.08 (N = 8), and on day 28 was 1.91 +/- SD 0.74 ml X (100 g X min)-1 (N = 7). However, the tendency of a decreasing SBF at the end of treatment was a clear trend, since SBF in 6 of 7 patients decreased during the third week and in the patient who was discharged on day 22, a decrease in the SBF was observed on days 14 and 21. The week-to-week changes in the SBF of lesional and nonlesional skin sites were parallel, r = 0.93, p less than 0.02. The decrease in SBF in psoriatics during successful antipsoriatic treatment might be a secondary thermoregulatory phenomenon due to a decreasing cutaneous blood flow. PMID- 4020161 TI - Inhibition of collagen production in scleroderma fibroblast cultures by a connective tissue glycoprotein extracted from normal dermis. AB - It was shown in a previous paper that a connective tissue glycoprotein (CTGP) extracted from normal rabbit dermis was able to inhibit total protein and collagen syntheses by normal dermis fibroblast cultures. In the present study, the effects of CTGP on scleroderma fibroblasts were investigated. [14C]Proline incorporation into total proteins of the supernatant was not significantly different from that found in controls. By contrast, the amount of collagen, expressed as percentage of total secreted protein, was far higher in scleroderma cultures than in normal ones (14.4% +/- 6.0% vs 4.6% +/- 0.9%). Addition of CTGP to the medium induced a concentration-dependent inhibition of [14C]proline incorporation into proteins from both control and scleroderma cells. In control cultures, no significant decrease of the percentage of collagen was observed, but over 60 micrograms/ml, both cytotoxic effects and inhibition of protein synthesis occurred. In scleroderma cultures, the inhibition was twice as effective on collagen as on noncollagen protein synthesis. The inhibition of collagen secretion was not related either to changes in collagen hydroxylation or to the intracellular catabolism of newly synthesized procollagen. PMID- 4020163 TI - Retinoids and cancer. PMID- 4020164 TI - Effects of topical retinoic acid on intracutaneously implanted S91 melanoma in mice. AB - Previous studies have demonstrated that retinoids possess antineoplastic properties against melanoma. The purpose of this study was to determine whether topically applied retinoic acid could prevent melanoma development in syngeneic mice after intracutaneous cell inoculation. Trans-retinoic acid in DMSO was applied daily for 28 days after melanoma implantation and tumor growth was quantitated by the uptake of [14C]thiouracil, a tracer compound specific for melanoma which is incorporated linearly according to the weight of the tumor. Marked reduction in tumor growth was noted at the highest concentration (0.1%) tested and lesser but significantly decreased tumor growth patterns were also realized at lower concentrations in a dose-dependent manner. Thus, topically applied retinoic acid is capable of inhibiting S91 melanoma growth in vivo. PMID- 4020165 TI - Role of solar conditioning in DNA repair response and survival of human epidermal keratinocytes following UV irradiation. AB - We have investigated the cumulative effects of sunlight exposure upon the excision-repair of UV radiation damage to DNA in epidermal keratinocytes from human donors of different ages as well as the possible effect on DNA repair of periodic conditioning of the cultured keratinocytes with sublethal UV radiation exposures. We have also compared the growth properties of UV-irradiated keratinocytes derived from habitually sun-exposed and nonexposed areas from the bodies of young and aged donors. DNA repair replication in keratinocytes from habitually sun-exposed facial skin and the less sun-exposed abdominal skin of middle-aged adults was found to be similar, with respect to both the UV dose response and the time course of repair after 20 J/m2, 254 nm. Growth and survival (after exposure up to 50 J/m2, 254 nm) were greater for keratinocytes from protected areas of the upper arm of young donors (under 18 years) than for cells from their own sun-exposed areas. Growth and survival were markedly reduced for all keratinocyte cultures from aged donors, especially those cultures developed from sun-exposed areas. Nevertheless, the DNA repair response to UV radiation was similar in all cases. The evident uncoupling of UV sensitivity from DNA repair capacity remains to be understood. Our studies confirm that the cumulative effect of sunlight exposure indeed contributes to some skin aging processes. However, we have found no indication that an overall reduction in capacity for excision repair of UV photoproducts in keratinocyte DNA accompanies senescence in human skin. PMID- 4020167 TI - In vitro phase II trial of recombinant interferon alpha-2 in gastrointestinal cancer. AB - The antitumor effects of recombinant interferon alpha-2 (rIF) on clonogenic tumor cells were investigated in 29 cases of gastrointestinal cancer. An in vitro response (greater than or equal to 50% inhibition of tumor colony-forming units) was observed in 17% of the tumors, including 2 of 8 pancreatic, 2 of 6 gastric, and 1 of 10 colon cancer specimens. The relative efficacy of rIF in tissue cultures of pancreatic and gastric tumors was further substantiated by the resistance against simultaneously tested single conventional cytostatic drugs. Preliminary results of comparative studies of cloned interferon alpha-2 and human purified leukocyte interferon (hlIF) in 2 human colon cancer cell lines and 11 fresh tumor specimens suggest similar trends in terms of colony inhibition in individual assays. However, the interpatient differences indicate an overall superiority of the natural preparation (P less than 0.02). PMID- 4020166 TI - An action spectrum for 8-methoxypsoralen-sensitized inhibition of DNA synthesis in vivo. AB - The wavelength dependence for 8-methoxypsoralen (8-MOP)-sensitized inhibition of scheduled DNA synthesis was investigated in the epidermis of albino hairless mice. Topical (0.1%) applications of 8-MOP followed by exposure to narrow bands from a monochromator in the range of 300-380 nm produced a dose-dependent inhibition of DNA synthesis. Prior treatment with 8-MOP did not alter the dose dependent inhibition of DNA synthesis following exposure to 300 nm and to 310 nm. By contrast, DNA synthesis inhibition following exposure to UVA wavelengths was seen only after treatment with 8-MOP. An action spectrum, constructed from the dose-response regression lines, showed peak effectiveness at 335 nm. Since the therapeutic usefulness of psoralen photochemotherapy may be related to inhibition of cell proliferation, it is suggested that light sources with peak emission in the 335-nm region would be more efficient than the commonly employed UVA blacklights. PMID- 4020168 TI - [Surgical treatment of tricuspid regurgitation in combined valvular diseases]. PMID- 4020169 TI - [Systemic-pulmonary artery shunts using expanded polytetrafluoroethylene (EPTFE) grafts]. PMID- 4020170 TI - [Bilateral simultaneous thoracotomy for unilateral spontaneous pneumothorax, with special reference to the operative indication considered from its contralateral occurrence rate]. PMID- 4020171 TI - [The role of functional left ventricular morphology in the selection of the mitral prosthesis]. PMID- 4020172 TI - [Evaluation of myocardial protection by coronary vascular resistance]. PMID- 4020173 TI - [The effects of hematocrit and aortic occlusion time in blood and crystalloid cardioplegia solutions]. PMID- 4020174 TI - [Comparison of three clinical methods of myocardial protection: the efficacy of cold blood coronary perfusion combined with cardioplegia]. PMID- 4020175 TI - [Experimental studies of left heart bypass using the centrifugal blood pump]. PMID- 4020176 TI - [Long-term results of tricuspid annuloplasty for tricuspid regurgitation with acquired mitral valvular disease]. PMID- 4020177 TI - [Abnormal branching of the left pulmonary artery to the lateral and posterior basal segments]. PMID- 4020178 TI - [Thromboexclusion with single permanent aortic clamp and temporary distal balloon occlusion for dissecting aneurysm]. PMID- 4020179 TI - [A case of patch aortoplasty without flow occlusion]. PMID- 4020180 TI - [Evaluation of an operative procedure for mitral stenosis--with special attention to the pre- and postoperative LV wall motion]. PMID- 4020181 TI - [Right ventricular volume growth following pulmonary valvotomy in pulmonary atresia with intact ventricular septum]. PMID- 4020182 TI - [Echocardiographic estimation of postoperative left ventricular function in congenital heart diseases with right ventricular over-load]. PMID- 4020183 TI - [A long-term result of tricuspid surgery for acquired tricuspid regurgitation]. PMID- 4020184 TI - [Characteristics of ventricular volume after Jatene procedure for complete transposition of the great arteries]. PMID- 4020185 TI - [Clinical study of diagnosis of the site of the origin of ventricular tachycardia by body surface maps]. PMID- 4020186 TI - [Nonresective operations for thoracic or thoracoabdominal aortic aneurysms]. PMID- 4020187 TI - [Pre- and late postoperative assessment of left ventricular function in patients with aortic regurgitation]. PMID- 4020188 TI - [Intraoperative electrophysiological delineation and histological study of the conduction system]. PMID- 4020189 TI - [A case of tricuspid regurgitation due to blunt chest trauma]. PMID- 4020190 TI - [Successful Jatene's operation for TGA type Taussig-Bing anomaly with straddling of the mitral valve]. PMID- 4020191 TI - [Ball thrombus of the left atrium: a case report of a successful removal]. PMID- 4020192 TI - [Torsion of the right middle and lower lobes after right upper lobectomy: a case report]. PMID- 4020193 TI - [Major aortopulmonary collateral-pulmonary arterial shunt for pulmonary atresia with ventricular septal defect and hypoplastic pulmonary arteries]. PMID- 4020194 TI - [Experience using the Mobin-Uddin vena cava umbrella filter]. PMID- 4020195 TI - [A case of Konno method for the infantile type of aortic valvular stenosis]. PMID- 4020196 TI - [Collection of human oocytes by percutaneous aspiration using ultrasound]. AB - Ultrasound-guided percutaneous follicular aspiration was performed in 10 patients taking part in our in vitro fertilization and embryo transfer (IVF-ET) program, in which laparoscopic egg retrieval had been recognized to be difficult, due to severe adhesions. Twenty-three follicles with a mean diameter of 23mm were aspirated, and 12 oocytes were recovered, giving a success rate of 52% per follicle. The overall egg recovery rate was 64% (9/14) per procedure. In 7 cases the procedure was carried out under local anesthesia, in 4 cases under subarachnoid block, and in the remaining 3 under general anesthesia. Egg recovery was better under spinal and general anesthesia (6/7) than local anesthesia (3/7). The only complication was a transient hematuria found in one patient. These results suggests that ultrasound-guided follicular puncture is useful for collecting oocytes in the IVF-ET program, when the routine laparoscopic approach is not applicable because of severe pelvic adhesions. PMID- 4020197 TI - Immunosuppressive high molecular glycoproteins in ovarian cancer ascites fluids. PMID- 4020198 TI - [Clinical evaluation of obstetrical and gynecological magnetic resonance imaging (MRI)]. PMID- 4020199 TI - Benign cystic teratoma of ovary containing a homunculus. PMID- 4020200 TI - [Ultrastructure of the ectopic endometrial glandular epithelium in five cases of adenomyosis--with particular reference to the normal proliferative endometrium and endometrial adenocarcinoma]. AB - Although we encounter endometriosis not infrequently, the exact nature of this entity has not yet been determined. In order to study the morphogenesis of this disease, we chose the adenomyotic glandular epithelium as distinct ectopic glands and examined them in the electronmicroscope, comparing them with the proliferative phase of the endometrium and the uterine body adenocarcinoma. Five cases were selected from 76 histologically proven cases of adenomyosis at our University. Epon blocks were ultrasectioned with a Porter MT II microtome, stained with uranium acetate and lead, and observed in a JEM 100 C electronmicroscope. The characteristics of adenomyotic glandular epithelium compared to the normal proliferative endometrium were: 1) expanded smooth nuclear membrane with scattered fine chromatin and zero to one irregularly surfaced nucleoli, 2) in cytoplasm, rough ER and free ribosomes are distinct, mitochondria are round to oval in shape with moderate irregularity, and microfibrillar structures and interdigitations are present in moderate amounts. Although there are few similarities to endometrial cancer, these findings would suggest that adenomyosis may be an intermediate between the normal proliferative endometrium and endometrial cancer. PMID- 4020201 TI - [Amniotic fluid 3,3',5'-triiodothyronine (reverse T3)]. AB - RT3(3,3',5'-triiodothyronine) levels in amniotic fluid and T4(thyroxine), T3(triiodothyronine), rT3 and TSH(thyroid-stimulating hormone) levels in maternal and cord serum were determined simultaneously by RIA. We also determined the activities of the monodeiodination of thyroxine to rT3 in placentas. Amniotic fluid rT3 and cord serum rT3 levels decreased, but T4, T3 and TSH levels increased with advancing gestational age. The activities of the monodeiodination in placentas decreased rapidly from midgestation, preterm to term. In maternal hyperthyroidism, amniotic fluid rT3 levels were markedly elevated. Moreover, there were significant positive correlations between amniotic fluid rT3 and maternal serum rT3 (r = 0.756, p less than 0.001, n = 26) and T4(r = 0.509, p less than 0.01, n = 26) in the normal 3rd trimester. We found significant correlations between amniotic fluid rT3 and fetal thyroid function as well as the activity of the monodeiodination in placenta after 17 weeks' gestation. But we couldn't find any such correlations in the 3rd trimester. These data suggest that the amniotic fluid rT3 in the 3rd trimester was affected by maternal thyroid function as well as fetal thyroid function and the activity of the monodeiodination in placenta. PMID- 4020202 TI - [Studies on the symptoms of EPH-gestosis patients one month after delivery]. AB - We investigated 1805 puerperants, after the twenty-fourth-week of pregnancy, who delivered from January 1st, 1981 till December 31st, 1982 in our hospital. 271 pregnancies were diagnosed as EPH-gestosis according to the new diagnostic standard in Japan (prevalence 15%). The severer the type of EPH-gestosis that had been diagnosed during pregnancy, the more symptoms they showed and the more often complications were diagnosed one month after delivery. In mild type as well as in severe type EPH-gestosis patients, if they had more than one symptom one month after delivery, they were more frequently diagnosed as having complications in pregnancy. In addition, those who had one or more symptoms one month after delivery often had shown symptoms of EPH-gestosis earlier in pregnancy. There were no significant correlations between the symptoms one month after delivery and the age of the mother, or between these symptoms and the time of delivery. Furthermore there was no significant correlation between these symptoms and the frequency of neonatal asphyxia, or the frequency of intrauterine death. These data suggest that symptoms one month after delivery of EPH-gestosis have some relation to complications in pregnancy. PMID- 4020203 TI - [Effect of dopaminergic agents on the endocrine profile in labor and early puerperium]. AB - The purpose of this study was to investigate the prolactin (PRL) releasing mechanism of the hypothalamo-pituitary axis during labor and early puerperium. Ten full-term gravidas during labor and 42 women in early puerperium were examined in this study. The plasma PRL levels rose significantly (p less than 0.001 approximately 0.05) after an intravenous bolus of 10mg metoclopramide (MCP). The peak values for PRL increase were 609.3 +/- 194.1ng/ml during labor and 447.0 +/- 62.3ng/ml in early puerperium. However, there were no significant differences in PRL response to MCP between these two groups. The plasma PRL levels dropped significantly (p less than 0.001 approximately 0.01) after an oral administration of 2.5mg bromocriptine (BRC), and the PRL release from the pituitary by MCP was suppressed significantly (p less than 0.001) by pretreatment with BRC in the puerperium. In addition, no significant changes in plasma 17 beta estradiol (E2), progesterone (P) and cortisol levels could be observed after MCP. We concluded that the control mechanism of PRL secretion remained unchanged during labor and early puerperium. PMID- 4020204 TI - [Reliability of the advice given at genetic counselling: follow-up study]. AB - A follow up investigation was carried out in order to estimate the reliability of the advice given at our genetic counselling clinic. Data were collected mainly by questionnaires sent by mail in November, 1983 to 556 clients counselled during the period January, 1976 - December, 1982. The outcome of 444 pregnancies for 361 clients was revealed. They were divided into three groups according to the risks estimated and suggested by the counsellors; below 2% (Group I), 2 - 9% (Group II) and 10% or more (Group III). The following results were obtained. The incidence of those who had not become pregnant following the day of counselling was higher in Groups II and III than in Group I. The rate of spontaneous abortion was higher in Group III than in Groups I and II. The incidence of pregnancies with children affected by birth defects for which the risks were estimated was 1.5% in Group I, 6.5% in Group II and 26.5% in Group III. Six to nine percent of babies of all groups suffered from other diseases such as intrauterine fetal death, congenital anomalies, developmental abnormalities or severe infectious diseases. The recurrence rate for regular trisomic Down's syndrome was 1.8%. These results suggested that the risk estimates and advice were quite reliable and helpful. PMID- 4020205 TI - [Study on placental blood flow in late pregnancy by intravenous 99mTc method]. AB - A method for the continuous recording of uteroplacental blood flow (PBF) in late pregnancies by using 99mTc-albumin has been described. The PBF curve of toxemia of pregnancy has been plotted to indicate small artery spasm in proving ischemic necrosis of placenta. In the PBF of placental insufficiency evidenced by the values for urinary E3, an unfavorable build-up and a delayed build-up time were observed. The pathologic diagnosis showed condensation, fusion and necrosis of villi. In the PBF in which a intrauterine fetal death (IUFD) was caused by placental factors, a sudden change in the PBF was observed showing the presence of an ischemia. In the PBF of pregnancy with diabetes, a large wave pattern change was observed indicating a decrease in the PBF. The pathologic diagnosis showed the fusion, hyalinization and necrosis of villi. The PBF wave patterns were classified into four kinds: normal pattern, angio-spasm pattern, delayed build-up pattern, circulation pattern. It has become clear that these abnormal wave patterns are frequently observed in toxemia of pregnancy, placental insufficiency and pregnancy with diabetes. PMID- 4020206 TI - [The ionic heterogeneity of human prolactin (PRL) from amniotic fluid]. AB - The ionic heterogeneity of prolactin (PRL) secreted in the human amniotic fluid was investigated using new precise chemical techniques. From five liters of amniotic fluid, the PRL fractions were purified with 70% ammonium sulfate precipitation, ethanol fractionation, desalting by gel filtration on Sephadex G 25, and ion-exchange chromatography using Mono Q on Fast Protein Liquid Chromatography (FPLC). The last FPLC was repeated until homogeneous preparations were obtained. Hormonal activity of each fraction was determined with a NIADDK radioimmunoassay (RIA) kit for human PRL. The PRL activity of the finally purified component was also assayed by radioreceptor analysis (RRA) using rat liver cell membranes as the receptor. From the amniotic fluid, seven components of the PRL were eluted at NaCl concentrations from 0.065M to 0.13M in 0.02M Tris HCl, pH 8.0. The RRA/RIA values of these seven components were different from each other (from 0.32 to 0.97). The lower the NaCl concentrations, the higher the RRA/RIA values were. The molecular weight of each component determined by gel filtration on TSK-SW 3000 with HPLC, was similar (MW 23,000) corresponding to "small-PRL". PMID- 4020207 TI - Effect of levamisole on bacterial index in BL and LL leprosy. AB - A 150 mg levamisole tablet once in every fortnight along with specific antileprosy drugs were administered to ten patients each in BL and LL groups of leprosy. A similar number of patients in each group receiving only specific antileprosy treatment served as controls. After 11/2 years of study a more significant improvement was noted in the bacteriological status in the levamisole treated group. Thus, levamisole can be used as an effective adjunct for quicker recovery in lepromatous patients. PMID- 4020208 TI - Minimum temperature felt as hot (MTH)--a new concept for grading the loss of temperature sensation in leprosy patients. AB - In order to grade the loss of the temperature sensation in the skin of leprosy patients, a newly designed instrument called the Temperature-Sensation-Testing and-Grading device has been employed to determine the minimum temperature felt as hot (MTH) at the skin area. The MTH in normal subjects was observed to vary from one region of the body to another; it was generally higher on the distal parts of the extremities compared to the proximal parts; and it was also higher on the lower extremities compared to the upper ones. The abdomen and the back generally had the lowest values. There were no variations according to age (11-80 years) or sex and no differences on symmetrical sites of the body. The MTH value, however, showed a dependence on the environmental temperature, the values being lower at low environmental temperatures and higher at high environmental temperatures. But at the same site and the same environmental temperature, the MTH value was found to be almost constant. Different individuals had different MTH values at the same body site and even at the same environmental temperature. The unaffected skin of leprosy patients showed values comparable to the controls. At the leprosy lesions, however, the degree of sensory loss could easily be determined in comparison with the MTH at the contralateral/adjoining unaffected skin. Out of 54 leprosy patients, 7 patients had no sensory loss; in 27 patients the loss varied between 1 degree C and 20 degrees C; while in 20 patients the loss was complete- they could not perceive even 50 degrees C as hot.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4020209 TI - Inhibition of antibody-dependent, cell-mediated cytotoxicity by serum from lepromatous leprosy patients. AB - Antibody-dependent cellular cytotoxicity (ADCC) and total and alternative pathway complement (C) activity were found to be normal in lepromatous leprosy (LL) patients in the presence of elevated circulating immune complexes (CIC) measured by the 125I-Clq binding assay. Heat inactivation (56 degrees C, 30 min) uncovered the ADCC inhibitory activity of LL sera. The effect of C was exerted both by interfering with the blocking action of CIC and by recovering ADCC activity of CIC-blocked effector cells. Heat inactivation allowed the expression of total and alternative C pathway fixing ability of the LL sera. Thus, immune complexes potentially able to block Fc receptor-dependent functions or capable of fixing C can be detected in LL sera. We postulate that compensatory mechanisms such as those described in vitro may contribute to maintain intact ADCC activity in vivo. PMID- 4020210 TI - Serum immunoglobulins, including IgG subclasses, in Vietnamese leprosy patients. AB - Levels of serum immunoglobulins were measured in healthy Vietnamese and in leprosy patients. Healthy Vietnamese had higher levels of IgG, IgA, IgM, and IgE than did healthy Dutch controls, as well as higher levels of three of the four subclasses of IgG (IgG1, IgG2, IgG3). Lepromatous leprosy patients had significant increases in all classes and subclasses of immunoglobulins, except for IgG2, in comparison with local controls. Tuberculoid leprosy patients had more IgG1, IgG3, and IgG4 than did local controls and had higher total IgG levels. The patients had no increase in autoantibodies against tissue antigens compared to local or Dutch controls. PMID- 4020211 TI - Muramidase (lysozyme) findings in sural and radial nerve biopsies in leprosy patients after varying periods of treatment. AB - Using the immunoperoxidase staining method, tissue muramidase (lysozyme) activity was studied in 34 nerve biopsies from leprosy patients and compared to findings in the skin. In a majority of lepromatous and borderline-lepromatous leprosy patients, the enzyme was seen to form a saccular pattern within the cells; whereas a granular pattern was found at the tuberculoid end of the leprosy spectrum, as well as during reversal reactions. Indeed, the most intense enzymatic activity was found in four patients with reversal reactions. Compared to the skin, muramidase activity was found to be more intense and persisted longer in the nerves. Successful antileprosy treatment reduced the enzymatic activity in both the nerves and the skin, but more so in the skin. Schwann cells and axons did not show muramidase activity, indicating that the muramidase positive cells are not of neuronal origin. Our results suggest that a high percentage of mononuclear cells infiltrating the peripheral nerves in leprosy are derived from blood monocytes. The function of tissue muramidase in leprosy is not yet clear. Its peculiar intracellular distribution pattern in the different forms of leprosy, however, warrants further study to elucidate its role in the pathogenesis of the disease. PMID- 4020212 TI - Psychosocial stress in Hansen's disease: a comparison with other chronic illness patients. AB - The present study investigated stress, as measured by a standardized life events scale, in Hansen's disease (HD) patients and as compared to renal patients and non-illness controls. Statistical analyses indicated that experimental groups were well matched on variables of age, sex, and marital status. Regarding analyses of the life events scale, significant differences were found across groups for negative change scores and total change scores. Post-hoc analyses revealed that the outpatient HD group and the renal group were significantly different from the non-illness controls. The results are viewed as support for the hypothesis that HD patients are similar to other chronic illness groups in terms of psychosocial characteristics. PMID- 4020213 TI - The patient with sensory loss. AB - The psychosocial ramifications of the loss of sensation are subtle and often are not perceived. One hundred Hansen's disease patients were interviewed concerning their experiences of living with sensory loss on their hands and feet. Their responses to the questions may assist medical practitioners in the treatment of the effects of the disease. PMID- 4020214 TI - Serum enzymatic changes following infection of mice with Mycobacterium lepraemurium. AB - Mice injected interperitoneally with 1.5 X 10(8) Mycobacterium lepraemurium develop progressive visceral alterations that are reflected in the lactic dehydrogenase (LDH), glutamate-pyruvate transaminase (GPT), and glutamate oxalacetate transaminase (GOT) levels. The rise in GPT and GOT levels starts earlier (about 30 days post-infection) than the rise in LDH activity (about 70 days), but the latter shows the most impressive increases. Differences between infected and control groups, however, reach statistical significance only at 75 days (LDH), 90 days (GOT), and 150 days (GPT) post-inoculation, still well before the appearance of obvious external signs of infection (about 240 days in our model). It is suggested that the ratio of enzyme levels in infected to enzyme levels in uninfected animals could be taken as a reliable index to follow the progress of the infection with M. lepraemurium. PMID- 4020215 TI - Biochemical alterations in the serum of armadillos (Dasypus novemcinctus) infected with Mycobacterium leprae. A preliminary report. AB - Armadillos (Dasypus novemcinctus) were inoculated with Mycobacterium leprae isolated from lepromas taken from untreated lepromatous patients or from the spleen of an armadillo previously infected with human M. leprae. The effect of the infection on the serum levels of lactic dehydrogenase (LDH), alkaline phosphatase (AlkP), glutamate-oxalacetate (GOT) and glutamate-pyruvate (GPT) transaminases was investigated. In general, there was a good correlation between positive evidences of infection and alterations in the levels of LDH, GOT, and GPT. Although elevations in LDH levels were more striking, elevations in GOT and GPT levels were more consistent with the disease. When an absolute increase in the total LDH activity was not observed in a M. leprae-infected animal, an increase in the level of LDH isozyme V was still clearly evident. Serum levels of alkaline phosphatase were not affected by the disease. The ratio GOT/GPT (greater than 1.0) in the infected animals reflected and supported the chronic nature of the disease and the liver involvement. The enzymatic alterations are not, however, specific for leprosy. PMID- 4020216 TI - Experimental leprosy in the mangabey (Cercocebus atys): necropsy findings. AB - A mangabey monkey (Cercocebus atys) was inoculated intravenously and intracutaneously with acid-fast bacilli (AFB) from a mangabey with spontaneously acquired leprosy. It developed generalized lepromatous leprosy and died 46 months after inoculation. Necropsy revealed severe lepromatous infiltrates in the skin, nasal mucosa, peripheral nerves, and testicles. Internal organs were only minimally involved. The lesions seen at necropsy were very similar to those seen in untreated cases of human lepromatous leprosy. These findings further substantiate the mangabey monkey as a suitable animal model for the study of lepromatous leprosy. PMID- 4020217 TI - Strategy for leprosy control. PMID- 4020218 TI - Standardized schemes for steroid treatment in ENL and reversal reactions. PMID- 4020219 TI - [Radiographic research on skeletal measurements and morphology of normal hand of Japanese. Part One: Adult]. AB - The present investigation was undertaken to develop a standard method of recording the bone measurements of the normal hand for use in comparative studies of genetic abnormalities of the skeletal system affecting the hand. The data for this study are obtained from the radiographs of the hands of normal 461 males and 565 females aged from 20 to 84 years. Measurements of length and width of all the phalanges and metacarpals are recorded. The phalangeal index and metacarpal index of each bone are obtained by dividing the length by the width. Frequencies of brachymesophalangy of the little finger and brachytelephalangy of the thumb are investigated. There are no significant differences between the bone of the right and left hand related to hand dominance. The radiographs of the hands of mother and son with the Marfan syndrome were compared with normal one. Metacarpal index and phalangeal index are useful for diagnosis of the Marfan syndrome. PMID- 4020220 TI - [A scanning electron microscopic study of denervated neuromuscular junctions]. AB - The morphological changes of the neuromuscular junctions (NMJs) caused by nerve transection have been examined by scanning electron microscopy in the peroneus longus muscle of the Chinese hamster. The synaptic grooves in the normal NMJs are deep labyrinthine depressions partitioned by ridges and contain numerous slit like subsynaptic folds. After denervation, the grooves become shallower with lower sarcoplasmic ridges, and the subsynaptic area of the muscle fibers gradually flattens as a whole. The subsynaptic area shows a plate-like sarcoplasmic elevation by 4 weeks and persists as a fusiform focal bulge on the atrophied muscle fiber after 4 weeks. Concurrently the subsynaptic folds decrease in number and transform into shallow pit-like invaginations. Any subsynaptic specialization has not been discernible after 16 weeks. Changes in acetylcholinesterase stainability at the NMJs have also been observed by light microscopy. No remarkable changes were noted until 4 weeks after denervation, thereafter, however, acetylcholine positive area became smaller showing more diffuse staining pattern. Atrophied muscle fibers often exhibit longitudinal splitting and the satellite cells tend to detach from the muscle surface. These evidences suggest a regenerative process which may take place during muscle degeneration. PMID- 4020222 TI - Biomechanical analysis for osteoarthritis of the ankle. AB - The study of three-dimensional model of the human arthritic ankle joint by the stress freezing photoelastic technique showed regional increases of stress distribution in contact area of the medial side of the talocrural joint and medial shift of the stress distribution center in the subtalar joint. From the study of the ankle joint in a contact stress analysis under a variety of conditions, the possible cause of primary or secondary osteoarthritis is discussed, and the joint instability resulting from lateral collateral ligament injuries might be one of the major cause of the disease. For the treatment of the disease, low tibial osteotomy with ligament plasty is considered to be effective. PMID- 4020221 TI - [Morphological study of the epiphyseal cartilage in cartilage matrix deficiency (CMD) mouse--a consideration on the roles and functions of cartilage-specific proteoglycan]. AB - Epiphyseal cartilages in mouse with cartilage matrix deficiency due to genetic failure to synthesize cartilage-characteristic proteoglycan were examined under light and electron microscope. Chondrogenesis and proliferation of chondrocytes seemed to occur, though extracellular matrix was small in amount and chondrocytes were packed closely without consistent orientation. In diaphysis, hypertrophic change of chondrocytes and perichondral ossification were observed. In the epiphysis, there was neither zone formation nor column formation, but hypertrophic chondrocytes and calcification in matrix were observed in the area adjacent to the bone shaft. Electron microscopy showed dilatation of rough endoplasmic reticulum, swelling of mitochondria and a large amount of lipid deposition in the chondrocyte. In the cartilage matrix, it was characteristic that a large number of thick collagen fibrils was arranged in parallel and few matrix granule was seen. These findings suggested that cartilage-characteristic proteoglycan was not essential for chondrogenesis, proliferation of chondrocytes and ossification, but were important for cytodifferentiation and chondrocyte activity. PMID- 4020223 TI - [Report on the diagnosis and treatment of muscular contracture. The Ad Hoc Committee of the Japanese Orthopaedic Association of Muscular Contracture]. AB - Muscular contracture due to repeated intramuscular injections raised urgent questions from the medico-legal standpoint when a large number of children with quadriceps contracture was found in Yamanashi Prefecture in 1973. In 1975, the Japanese Orthopaedic Association formed an Ad Hoc Committee on Muscular Contracture to investigate the diagnosis and treatment of this particular condition. Since then, the Committee has studied the symptomatology, diagnosis, natural history, orthotic and operative treatment of quadriceps, deltoideus and gluteus contractures. The results have been reported annually to the Japanese Orthopaedic Association, and guidelines for diagnosis and treatment have been made available to its members. Quadriceps contracture can be classified into three types: the rectus femoris, vastus, and mixed types. The rectus femoris type represents 80 to 90 per cent of cases with quadriceps contracture, while the vastus type is quite rare. In both the rectus femoris and mixed types, operative treatment is suggested when the knee flexion is limited to 30 degrees or less in the prone position. Transverse division of the rectus femoris at the muscle belly is the standard operative procedure recommended for the rectus femoris type and gives very satisfactory results in most cases. In the mixed type, an additional division of the scarred portion of the vasti is needed. The ideal age for such procedures is near or after the end of growth. The vastus type is difficult to cure, but to improve the condition to a certain extent an operation is suggested when the knee flexion is limited to 45 degrees or less in the supine position. The operative procedure recommended is either release of the affected vasti at their insertion to the patella or Z-lengthening of the common tendon of the quadriceps. In deltoideus contracture, the Committee proposed a scoring system for evaluating the severity with the grade of abduction contracture and the opposite shoulder test as parameters. A score of 5 points or more indicates operative treatment. The operative procedure recommended is release of both the acromial part and the anterior fibers of the spinal part of the deltoideus. The ideal age for this procedure is 12 years or older. A dent produced by the operation distal to the acromion, however, has to be regarded as a cosmetic complication. To avoid this complication, advancement of the severed fibers of the deltoideus from the scapular spine to the acromion is needed. Such an advancement procedure is suitable for children of 14 or 15 years of age and leaves the natural round contour of the shoulder intact.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 4020224 TI - [Preparation of the acetabulum to correct severe acetabular deficiency for total hip replacement--with special reference to stress distribution of the periacetabular region after operation]. AB - The author analysed the radiological results of eighty-three total hip replacements in the patients with severely defective acetabulum secondary to congenital hip dysplasias or failed total hip replacements, after an average follow-up period of three years, paying particular attention to socket loosening. The patients with congenital hip dysplasias were divided into the following four groups: Group 1: The sockets were placed above the level of true acetabulum. Group 2: The sockets were placed in the true acetabulum with the cement used as a filler superolaterally. Group 3: The sockets were placed in the true acetabulum with bone grafts. Group 4: Eccentric sockets were placed in the true acetabulum. The incidence of radiological loosening of the socket was 50% in the group 1, 13% in the group 2, 6% in the group 3 and 75% in the group 4. The patients who underwent revision for socket loosening were also divided into two groups, the one whose acetabula were reconstructed with bone grafts and the other without bone graft. The incidence of radiological loosening of the socket was 28% in the group with bone grafts and 72% in the group without bone graft. The major factor that may have been responsible for socket loosening in these cases was considered to be poor mechanical condition around the socket due to bone deficiency. Two dimensional finite element analysis was performed to establish the stresses in the periacetabular region after total hip replacement for acetabular deficiency. Model variations include, the conventional plastic socket of 44 mm outside, 28 mm inside diameter placed in false acetabulum or in high level, (2) in true acetabulum using bone cement as a filler, (3) in true acetabulum with bone graft and (4) eccentric socket placed in true acetabulum without bone graft. The ratio of von Mises stress to yield stress of each element were calculated. The results demonstrated that in the periacetabular region, the area superomedial to the socket was at high risk in each model. The area in periacetabular bone where the ratio of von Mises stress to yield stress was more than 20% was almost the same in model (1), (2), (4) and about a half of them in model (3). In conclusion, the most effective method to prevent the socket loosening after total hip replacement in the patient with deficient acetabulum was considered to reconstruct the new spherical acetabulum at anatomical position with bone graft. PMID- 4020225 TI - [Another new etiology of vertebral artery insufficiency--a case of dynamic entrapment of the vertebral artery by the cervical nerve]. AB - In the etiology of vertebral artery insufficiency, cervical spondylosis with uncal osteophyte, Power's syndrome, A-V malformation and atheromatous narrowing have been recognized. We recently experienced a patient with episodic vertigo and hyposthenia of the left side of the body on rotational movement of the neck. On surgical exploration of the atlanto-axial area of the vertebral artery where dynamic constriction of the artery could be observed by angiography, we found that the right vertebral artery was entrapped and constricted by the anterior branch of the second cervical nerve with fibrous adhesion after injury. With the release and resection of the injured nerve, the patient became free of any vertigo or hyposthenia. Although this kind of etiology involving entrapment constriction of the vertebral artery by the cervical nerve after trauma has not been reported at all in the literature, we should always keep this in mind when dealing with patients with cervical vertigo after trauma. PMID- 4020226 TI - [Calcinosis universalis with hyperphosphataemia--successful treatment with phosphorus deprivation]. AB - Seven year old boy with calcinosis universalis associated with high serum phosphorus was reported. Over one year's treatment with aluminum hydroxide up to 18 grams per day have reduced calcified mass remarkably, while serum phosphorus levels were remaining still above the normal range. Concomitant use of probenecid seemed to be effective in reducing serum phosphorus levels as well as decreasing the calcified mass. Pathogenetic mechanisms of soft tissue calcification in calcinosis universalis is not clear, but in this case hyperphosphataemia is considered to be one important factor accelerating soft tissue calcification. Although hyperphosphataemia associated with tumoral calcinosis has been frequently observed, no report is yet available on calcinosis universalis associated with hyperphosphataemia. This case might represent one unique type of calcinosis. PMID- 4020227 TI - [Gait analysis in hemiplegic patients after gait training or surgery of a foot deformity]. AB - The change of gait in stroke patients after gait training or surgery for foot deformity was analyzed according to walking cycle and gait speed and cadence by means of the accelorometer or the large force plate. The results were summarized as follows. Twenty patients receiving gait training. Variation of the stride duration decreased gradually on both sides. The stance phase and the double support phase had the tendency to demonstrate equal percentage on both sides, decreasing in the unaffected side. The percentage values were higher than those in the normal person except a few cases. The cadence increased in all cases except one. Twenty-two patients following surgery for foot deformities. Walking cycle revealed almost the same result as that of cases receiving gait training. The percentage of the double support phase in the unaffected side characteristically approached that of the affected side after surgery, suggesting surgical benefits. Cadence decreased in 7 cases, while gait speed increased in all cases. It may come from the wider stride length after surgery. PMID- 4020228 TI - [Orthopedic ceramic implant--recent progress]. PMID- 4020229 TI - English abstracts of proceeding of the Twenty-second Congress of the Japan Society for Cancer Therapy. Tokyo, Sep. 26, 27, 28, 1984. PMID- 4020230 TI - Deep-freezing and transfer of human embryos. AB - Studies on the cryopreservation of 162 four-cell and eight-cell human embryos indicate that morphological survival and pregnancies can be achieved by specific techniques of freezing and thawing. Survival rates are highest when embryos are cooled at 0.3 degrees C/min to -80 degrees C in the presence of 1.5 M dimethylsulfoxide (DMSO) and thawed at +8 degrees C/min from -80 to +4 degrees C. Morphological survival of four-cell and eight-cell human embryos after freezing and thawing is not affected by irregularites in blastomere size or the presence of small cytoplasmic fragments. Light and electron microscopic examination of fixed specimens indicates a good correlation between the appearance of frozen thawed embryos at the dissecting microscope level and the extent of cryoinjury. Sixty-eight of 136 four-cell and eight-cell embryos (50%) survived with half or more of their blastomeres intact when cooled to low temperatures and thawed at the rates described. The transfer of these 68 embryos into 45 patients resulted in nine pregnancies. PMID- 4020231 TI - Analysis of human spermatozoa before and after processing for in vitro fertilization. AB - Washed incubated spermatozoa processed for in vitro fertilization were compared to the spermatozoa from the same unprocessed ejaculate in 31 randomly selected normal males (Group 1) and 7 subfertile males (Group 2). In Group 1 there was a significant increase in motility (P = 0.001) as well as a significant increase in normal morphology (P = 0.001). All categories of morphologically abnormal sperm decreased, with a significant decrease in those exhibiting small heads (P = 0.01), tapered heads (P = 0.01), cytoplasmic droplets (P = 0.001), bent midpieces (P = 0.01), or coiled tails (P = 0.02). There was also a significant decrease in immature germ cells (P = 0.001) as well as white blood cells (P = 0.02). Group 2 also showed a significant increase in motility (P = 0.01) and a significant increase in normal morphology (P = 0.01). There was a decrease in various categories of abnormal sperm, with a significant decrease in sperm with cytoplasmic droplets (P = 0.02). PMID- 4020232 TI - A comparison of personality characteristics between in vitro fertilization patients and other infertile patients. AB - Fifty patients of an in vitro fertilization (IVF) program were compared to 25 individuals undergoing fertility investigation other than IVF. Each subject was given the California Psychological Inventory (CPI) and a social history interview during which behavioral signs of anxiety were noted. The CPI profile indicated the IVF subjects to be higher on characteristics of ambitiousness, creativity, and independence. No major differences were noted on the interview questions and behavioral ratings. Both groups may view IVF as a possible treatment for their infertility; however, the IVF patients have certain personality characteristics which make them more likely to actually become involved. PMID- 4020233 TI - In vitro fertilization and embryo transfer in Pretoria, South Africa. PMID- 4020234 TI - Seminal bacterial pathogens and in vitro fertilization. PMID- 4020235 TI - Pregnancy without ovarian function. PMID- 4020236 TI - Program for in vitro fertilization and embryo transfer, Department of Obstetrics and Gynecology, University Central Hospital, Turku, Finland. PMID- 4020237 TI - In vitro fertilization and embryo transfer: the Johns Hopkins Hospital, Baltimore, Maryland. PMID- 4020238 TI - Initial experience with in vitro fertilization and embryo transfer at the University of Calgary/Foothills Hospital. PMID- 4020239 TI - Pregnancies following the frozen storage of expanding human blastocysts. AB - Human blastocysts were frozen in Earle's solution containing pyruvate and human serum, using glycerol as cryoprotectant, and stored in liquid nitrogen. Thawed blastocysts were replaced in 11 patients, which resulted in two pregnancies. One blastocyst giving a pregnancy was hatching when replaced. Three parameters appeared to be important for embryo survival and implantation: the interval between ovulation and replacement of the thawed blastocysts, satisfactory embryonic development before freezing, and the stage of blastulation when cooling began. PMID- 4020240 TI - Legal issues raised by in vitro fertilization and embryo transfer in the United States. PMID- 4020241 TI - Maternal blood platelet physiology and luteal-phase endocrinology as a means of monitoring pre- and postimplantation embryo viability following in vitro fertilization. AB - The discovery that the fertilized mouse ovum triggers an increased demand for platelets and results in thrombocytopenia during the preimplantation phase of pregnancy provides a monitor for embryo survival and viability. This paper reports a study in which the platelet count was significantly reduced throughout the human preimplantation phase of pregnancy and returned to normal following embryo implantation. The human embryo was shown to produce a platelet activating factor in vitro which caused the reduction in platelet count after embryo transfer. This factor in the embryo culture medium could be measured using a bioassay which provided a means of assessing embryo viability prior to transfer. Some women showed no reduction in platelets after transfer. These embryos failed to produce a platelet activating factor in vitro and pregnancy was not established. Other women displayed a reduction in platelets following transfer but failed to become pregnant. All of these women had elevated luteal-phase plasma E2 levels compared to pregnant patients, which may have interfered with the implantation process. Our observations provide a possible rapid and simple means for monitoring the viability of human embryos cultured in vitro and the survival of embryos in utero. PMID- 4020242 TI - Heart cells in culture: a model of myocardial iron overload and chelation. AB - The effect of iron loading and chelation was studied in heart cell cultures obtained from newborn rats. Radioactive iron uptake per 2 X 10(6) cells/24 hr was 3.8% for 59Fe-transferrin, 15.8% for 59Fe-ferric ammonium citrate (FeAC) at 20 micrograms Fe/ml in 20% serum, and 37.1% for 59FeAC at 20 micrograms Fe/ml in serum-free medium. About one third of the cellular radioactive iron was in ferritin and the rest in an insoluble lysosomal fraction. Iron uptake was almost completely inhibited by reducing the incubation temperature from 37 degrees C to 10 degrees C. Intracellular concentrations of malonyldialdehyde (MDA) were doubled after 15 minutes of iron loading and reached maximal concentrations at 3 hours. Conversely, iron mobilization by deferoxamine at concentrations ranging from 0.025 mmol/L to 0.3 mmol/L resulted in normalization of cellular MDA concentrations, in direct proportion to the amounts of iron removed. These findings indicate that cultured myocardial cells are able to assimilate large amounts of nontransferrin iron and that iron uptake and mobilization are associated with striking changes in lipid peroxidation as manifested by the respective increase and decrease in cellular MDA concentrations. PMID- 4020243 TI - Role of ductular bile water reabsorption in canine bile secretion. AB - To quantitate ductular and/or ductal bile water reabsorption and to define its role in hepatic bile formation, spontaneous and taurocholate-stimulated bile flow and composition were measured in anesthetized dogs postprandially (n = 4) and after a 24-hour (n = 4) and a 48-hour (n = 4) fasting period. Spontaneous bile flow in fed dogs (0.344 +/- 0.116 microliter/min/gm liver tissue) was significantly higher than that in 24-hour (0.179 +/- 0.046 microliter/min/gm) and 48-hour fasted animals (0.096 +/- 0.085 microliter/min/gm). One 48-hour fasted dog was virtually cholestatic (spontaneous bile flow 0.004 microliter/min/gm), and another 48-hour fasted animal had a mean bile flow rate as low as 0.036 microliter/min/gm. Calculated ductular bile water reabsorption (carbon 14 erythritol biliary clearance minus bile flow) was the same in the three groups of animals (0.166 +/- 0.056, 0.208 +/- 0.033, and 0.204 +/- 0.055 microliter/min/gm, respectively). Administration of sodium taurocholate (0.5 to 2.0 mumol/min/kg) revealed intact canalicular secretory capacity in all dogs, and no change in bile water reabsorption rate was observed during choleresis. Bile chloride and bicarbonate concentrations during spontaneous secretion were significantly lower in 48-hour fasted dogs when compared with fed animals. In the two 48-hour fasted dogs with a very low rate of spontaneous bile flow, chloride and bicarbonate concentrations in hepatic bile were as low as those seen in gallbladder bile (5 to 10 mEq/L) and increased during taurocholate choleresis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4020244 TI - Studies on the purification of thrombopoietin from kidney cell culture medium. AB - A thrombocytopoiesis-stimulating factor (TSF) has been purified from human embryonic kidney (HEK) cell culture medium. In the initial purification step, crude HEK cell culture medium was fractionated with saturated ammonium sulfate (step I). The proteins precipitated by 40% to 60% and 60% to 80% ammonium sulfate saturation increased the percent of sulfur 35 incorporation into platelets of assay mice (P less than 0.01). The ammonium sulfate-precipitated proteins that contained significant TSF activity were further refined on Sephadex G-75 columns (step II). The fraction containing the highest specific activity (greatest 35S incorporation into platelets of assay mice per milligram of protein) was further purified by diethylaminoethyl (DEAE)-cellulose column chromatography (step III). TSF activity was eluted from the columns between 0.3 and 1.0 mol/L NaCl. Additional Sephadex chromatography of post-DEAE-chromatographic preparations further increased the purity of the TSF (step IV). TSF from this four-step procedure was further processed on a DEAE-high-performance liquid chromatography (HPLC) column (step Va) or size exclusion (SE)-HPLC columns (step Vb). After HPLC, the activity was localized in a region corresponding to a retention time of 6 to 8 minutes for the DEAE-HPLC, but longer times were found after SE-HPLC. TSF was further purified by additional sodium dodecyl sulfate-polyacrylamide gel electrophoresis and SE-HPLC (step VI). The final product had significant TSF activity and represented a purification of approximately 500,000-fold. It was also shown that the isoelectric pH of partially purified TSF was 4.7 and the molecular weight of the more highly purified preparation was approximately 32,000. After extraction by a combination of chromatographic procedures, a single homogeneous product was obtained. PMID- 4020245 TI - New methods for the release of volatile sulfur compounds from human serum: its determination by Tenax trapping and gas chromatography and its application in liver diseases. AB - New methods are described for the release of sulfur volatiles from human serum or whole blood and for its determination by Tenax trapping and gas chromatography by use of a specific sulfur detector. Methanethiol (MT) is covalently bound in serum in at least two different ways. One fraction of MT is released by addition of acid and is covalently bound to a compound with a mol wt less than 500, probably as methyl-beta-D-thioglucuronide. Another fraction of MT is released by reaction with dithiothreitol and is covalently bound to proteins in a disulfide linkage. No significant differences were observed in the protein-bound MT fraction between normal individuals and patients with cirrhosis. In contrast, the acid hydrolyzable MT fraction was significantly elevated (P less than 0.0001) in the group with cirrhosis (0.41 +/- 0.19 mumol/L, mean +/- SD, n = 39) compared with the normal group (0.22 +/- 0.04 mumol/L, n = 21). The acid-hydrolyzable MT fraction is excreted in the urine. The concentration in normal persons amounted to 9 to 37 mumol/L. Dimethylsulfide (DMS) was measured in whole blood. There was a close correlation between venous blood DMS concentration and its concentration in breath. Dimethyldisulfide was not present in detectable amounts in the blood of normal individuals. Ethanethiol was absent in the serum and blood of all studied subjects. PMID- 4020246 TI - Cerebral acetylcholine and energy metabolism changes in acute ammonia intoxication in the lower primate Tupaia glis. AB - Ammonia levels are elevated in many patients with hepatic encephalopathy. This observation, coupled with animal studies showing an encephalogenic role for ammonia, has led to the concept that ammonia is an important toxin in the production of neurologic symptoms. Studies in rodents have shown that ammonia alters cerebral energy metabolism in the reticular formation, an area important in the modulation of consciousness. Our study was undertaken to extend these observations to the lower primate Tupaia glis, the tree shrew. The energy metabolites glucose, glycogen, lactate, adenosine triphosphate, and phosphocreatine were measured in the reticular formation by microanalytic techniques and enzymatic cycling. Acetylcholine was measured in brain regions by gas chromatography. Acetylcholine levels were increased significantly only in the medulla-pons and diencephalon in the coma stage. The energy metabolites glucose, glycogen, and phosphocreatine were decreased in reticular formation cells during the coma, whereas lactate was increased. During the precoma, glycogen and phosphocreatine were decreased. It appears, therefore, that the tree shrew has a metabolic response to ammonia similar to that of mice. A lowering of energy metabolism in the area of brain-regulating consciousness may act to place the animal in a coma. This coma in turn acts to decrease overall metabolic demand, which allows the animal an opportunity to conserve its threatened energy reserves. PMID- 4020247 TI - A randomized blind study comparing standard heparin and a new low molecular weight heparinoid in cardiopulmonary bypass surgery in dogs. AB - Postoperative hemorrhage remains a serious complication in cardiopulmonary bypass (CPB) surgery. In our study, alternative anticoagulation with a new low molecular weight (LMW) heparinoid (Org 10172) was compared with a standardized heparin regimen. A preliminary dose-finding study indicated the minimal effective heparinoid dose to be 260 anti-Xa U/kg body weight, which was comparable to the standardized heparin regime, as revealed by similar plasma anti-Xa values. The following randomized open pilot study in 12 mongrel dogs undergoing CPB showed the heparinoid to be as effective as heparin, with an additional advantageous decrease in postoperative blood loss in the Org 10172 group. Our randomized blind study in 16 mongrel dogs undergoing CPB was performed to confirm previous results. Both antithrombotic agents were effective in the prevention of clot formation within the extracorporeal circuit. Hematocrit values and erythrocyte and platelet counts showed no significant intergroup differences. Post-CPB leukocyte counts revealed a significantly more rapid increase in the group given heparinoid (P less than 0.05). In the group given heparin, the expected prolongations of both the thrombin time (TT) and activated partial thromboplastin time (APTT) were noted, whereas in the group given heparinoid, only a transient peak prolongation of the TT after dose administration was revealed, and no significant prolongation of the APTT. Mean anti-Xa plasma levels were similar during CPB, showing a rapid decrease in the group given heparin on protamine administration, as did the APTT. Assessment of the operating field indicated an elevated intraoperative blood loss in the group given heparin. Postoperative blood loss measured over a period of 2.5 hours after closure of the thorax was significantly lower in the group given heparinoid than in the heparinized animals (625 +/- 100.0 ml, mean +/- SD, and 806 +/- 178.2 ml, respectively; P less than 0.05). Our observations suggest that the LMW heparinoid Org 10172 has an increased benefit/risk ratio over standard heparin and is effective in CPB in dogs. Additional investigations in humans should verify the possibility of use of this substance as an alternative means of anticoagulation during CPB in patients in whom heparin is relatively contraindicated. PMID- 4020248 TI - Ventricular myocardial catecholamines in primates. AB - We report myocardial catecholamine levels in primate ventricles assayed by high pressure liquid chromatography with electrochemical detection. The norepinephrine content of the left ventricles of 11 monkeys (four rhesus and seven cynomolgus) was 1391 +/- 362 ng/gm (+/-SD) with a definite gradient from base (highest) to apex (lowest concentration). Dopamine and epinephrine were present in much lower concentrations (51.8 +/- 24.5 ng/gm and 59.2 +/- 20.0 ng/gm, respectively), but were similarly distributed throughout the left ventricle. There was considerable variation in norepinephrine concentration between animals, but the dopamine/norepinephrine ratio was very consistent within a given animal, averaging 3.7% +/- 1.4%. These values are probably indicative of what normal concentrations of catecholamines are likely to be in humans, and provide a basis for interpretation of results obtained in disease studies. PMID- 4020249 TI - Antihypertensive effect of riboflavin analogues in spontaneously hypertensive rats. AB - Our study was designed to use the antimineralocorticoid property of the riboflavin analogue 7,8-dimethyl-10-(3-chlorobenzyl)isoalloxazine (CBI) to investigate the involvement of mineralocorticoids in the hypertension of the Kyoto strain of the spontaneously hypertensive rat (SHR) and Dahl salt-sensitive (S) rat. Wistar Kyoto (WKY) mildly hypertensive rats were used as controls. The administration of the riboflavin antagonist CBI at 5.0 mg/kg body weight twice weekly for 7 weeks lowered the systolic blood pressure (SBP) of the unanesthetized SHR from 188 +/- 7 mm Hg to 148 +/- 2 mm Hg (P less than 0.05). This was concurrent with a 36% and 11% decrease in iliopsoas muscle Na+ concentration and water content, respectively. The simultaneous administration of CBI and hydrochlorothiazide (HCTZ) reduced the SBP to 126 +/- 4 mm Hg (P less than 0.05). There was a profound suppressive effect of CBI on the secondary hyperaldosteronism generated by HCTZ (17.6 +/- 4.3 vs. 50.4 +/- 7.2 ng/dl, P less than 0.05), which was also reflected in the iliopsoas muscle K+ concentration. The effects of CBI on the SBP and iliopsoas muscle Na+ and K+ concentrations of age-matched WKY mildly hypertensive control rats were qualitatively similar to the effects on the SHR. In contrast to the SHR and the WKY rats, the administration of CBI for 8 weeks at 5.0 mg/kg body weight twice weekly to the Dahl S rats did not reduce their mean SBP (205 +/- 5 vs. 200 +/- 4 mm Hg, not significant). CBI treatment did not significantly decrease iliopsoas muscle Na+ concentration or water content.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4020251 TI - Pulmonary aspiration of gastric contents. PMID- 4020250 TI - Conversion of atrial fibrillation to normal sinus rhythm during hyperkalemia. PMID- 4020252 TI - Evaluation of the Driver Limitation Program in Kentucky 1964-1984. PMID- 4020253 TI - Selective indications for subtotal abdominal hysterectomy. PMID- 4020254 TI - Bacteriological features and chemotherapy of adult acute purulent otitis media. AB - Eighty-eight patients from 16 to 79 years old, with acute purulent otitis media, were bacteriologically examined at the Otorhinolaryngology Department of a primary care hospital in Tokyo from July 1979 to May 1983. Fifty-six patients underwent paracentesis, and 32 patients exhibited otorrhea due to previous spontaneous perforation of the tympanic membrane. Bacteriologic cultures revealed the presence of Streptococcus pneumoniae (62.5 per cent), including S. pneumoniae Type III (28.1 per cent), Haemophilus influenzae (10.5 per cent), Staphylococcus aureus (11.5 per cent), and Streptococcus pyogenes (7.3 per cent). S. pneumoniae Type III had a notably high detection rate in patients from 50 to 79 years old (50-75 per cent). Because Haemophilus influenzae was detected at a relatively high rate in patients of all ages, if can be considered as a major causative pathogen of AOM. In 44 patients, selected mainly from those who underwent paracentesis, a comparative study of bacteria found in middle ear fluid and naso pharyngeal mucus revealed the same bacteria in 43 out of 44 cases (97.7 per cent), indicating the presence of bacterial infection through the auditory canal. Antibiotics were selected according to an Expected Efficacy Index (EEI), the antibiotic of first choice being Ampicillin or Cefaclor. PMID- 4020255 TI - Histochemical study of cartilage autografts in tympanoplasty. AB - Histochemical examination of lactic dehydrogenase enzyme activity was used to detect the effect of certain factors on the viability of cartilage autografts in the middle ear. The study shows that the presence of perichondrium on both sides of the strut and placing the lateral end of the strut increase the chance of survival of chondrocytes. On the other hand, middle ear infection has a very bad effect on the viability of chondrocytes. The length of the strut and the presence of silastic film in the middle ear have been found to be unimportant as far as the survival of the graft is concerned. PMID- 4020256 TI - Endaural cerebral hernia. PMID- 4020257 TI - A controlled study of the suppression of tinnitus by lidocaine infusion: (relationship of therapeutic effect with serum lidocaine levels). AB - The relationship between serum lidocaine levels and tinnitus relief was assessed in 5 patients during intermittent intravenous infusions of the drug. Experiments were conducted under controlled conditions in that neither the attending physician nor the patient was aware of whether active drug or placebo was being infused at any particular time. A significant relationship between serum level and effect was observed in two patients. In the remaining patients this relationship was not readily apparent but there was still a trend for a better response to be seen at higher levels. A satisfactory response was generally seen at levels above 1 microgram/ml. The results are consistent with the hypothesis that the transient nature of the symptomatic relief caused by lidocaine is related to the fast clearance of the drug from the body. PMID- 4020258 TI - A comparison of the effects of eighth nerve section with lidocaine on tinnitus. AB - The success rate of eighth nerve section in abolishing tinnitus is disappointing and the results generally unpredictable. A comparison of the effects of a bolus intravenous injection of lidocaine with the effects of nerve section is reported: it presents some evidence that the response to lidocaine may be of value in selecting patients for nerve section, and further it may shed some light on the site of action of lidocaine in suppressing tinnitus. PMID- 4020259 TI - Electrocochleographic findings and the effects of lidocaine on tinnitus in non hearing ears. AB - In the preceeding report (Jackson, 1985) the author produced evidence which brought into question the widely held view that, in abolishing tinnitus, lidocaine was acting 'centrally'. This present investigation is another approach to attempt to narrow the site of action of lidocaine in abolishing tinnitus. During a four-year period, patients suffering from strictly unilateral tinnitus which was referred to, and therefore apparently arising from, an ipsilateral 'dead' ear, underwent electrocochleography. Additionally, the subjective effect on the tinnitus of a bolus injection of lidocaine was recorded. Nine patients were available for this study, which appears to show a correlation of the results of the electrocochleogram and the effects of the lidocaine injection, although the numbers are small. PMID- 4020260 TI - Brain stem auditory evoked potentials and blink reflexes in multiple sclerosis. AB - Brain stem auditory evoked potentials (BAEP) and the blink reflex (BR) were recorded from 50 patients with a wide spectrum of multiple sclerosis, to determine whether the combination of the two tests of brain stem function would yield a higher rate of abnormality than each test performed alone. Sixty-four per cent of patients had a BAEP abnormality and fifty-two per cent had an abnormal BR, but when the results were combined, seventy-six per cent were abnormal. The blink reflex was abnormal in all patients with symptoms suggestive of trigemino facial pathology. PMID- 4020261 TI - The use of the latissimus dorsi muscle flap for posterior scalp defects. PMID- 4020262 TI - Pseudocysts of the auricle. AB - Pseudocyst of the auricle is a distinct clinical entity with certain characteristic features. These cysts occur more frequently in Chinese and develop spontaneously, without trauma or infection. The cysts contain clear yellow coloured fluid. A simple but effective method of treatment is described. PMID- 4020263 TI - A case of congenital conductive deafness. An audiometric diagnosis. PMID- 4020264 TI - Lightning-induced acoustic rupture of the tympanic membrane: (a report of two cases). PMID- 4020265 TI - Abscess of the nasal septum complicating isolated acute sphenoiditis. PMID- 4020266 TI - Fibrodysplasia ossificans progressiva presenting acutely as a submandibular swelling. PMID- 4020267 TI - A five-year follow-up of preformed, autologous ossicles in tympanoplasty. PMID- 4020268 TI - Nasal fractures in children: influence on the development of the nose. AB - Fifty-seven patients between the ages of zero and 16 years, treated for nasal fractures during childhood by means of closed reduction, have been subjected to follow-up examination after development of the nose has ceased. These patients have been compared to a control group of 50 persons without any known nasal trauma. No difference was found between the two groups with regard to functional complaints, but deviations of the osseous and cartilaginous pyramid, humps and saddle formations, as well as spine formations and deviations of the septum, were particularly prevalent in the fracture group. Crista formation and angulation were found to be equally frequent in both groups. The findings are discussed. PMID- 4020269 TI - The importance of nasal fractures during different growth periods of the nose. AB - Fifty-seven patients who had sustained nasal fractures during childhood were divided into three groups, according to the age at which the fracture had taken place. These three groups were based on the normal periods of development of the nose. They were compared with regard to possible sequelae after fracture. The results are discussed and an example from each group is shown. PMID- 4020270 TI - An evaluation and clinical study of severe epistaxis treated by arterial ligation. AB - Forty-three cases of intractable epistaxis treated by major arterial ligation are described, with follow-up in 41 cases of up to 11 years. It would appear that this treatment is effective in the control of epistaxis, and there was no evidence of any long-term detrimental effect on the nose, or of any significant mortality. External carotid artery ligation is advocated in the elderly and debilitated case, whilst internal maxillary artery ligation together with anterior ethmoidal artery ligation is indicated in the younger age group, or in the elective case. Evaluation of the results is discussed together with alternative methods of management. PMID- 4020271 TI - Reconstruction of the midfacial region after cancer surgery. PMID- 4020272 TI - The enigma of post-radiation oedema and residual or recurrent carcinoma of the larynx and pyriform fossa. AB - Persistence of significant laryngeal oedema following radiotherapy presents the surgeon with a diagnostic dilemma. Though the oedema may represent a prolonged response to irradiation, the possibility of residual carcinoma must be considered. Several authors have commented upon it and have suggested frequent biopsies to prove the presence of residual or recurrent neoplasm (Ward et al., 1975; Lederman, 1970; Calcaterra et al., 1972). Some reluctance to laryngeal biopsy has been exercised to avoid inciting a fulminant perichondritis. However, the difficulty of obtaining a positive biopsy in a post-irradiated case is well known, and repeated negative biopsies do not exclude the presence of a residual tumour. The present paper studies 52 histopathologically proven cases of carcinoma of the larynx and laryngopharynx which had received radiotherapy earlier. These cases underwent salvage radical surgery on clinical suspicion of residual/recurrent tumour, manifested by persistence of significant laryngeal oedema and/or fixation of the larynx. No positive biopsies had been obtained following radiotherapy. PMID- 4020273 TI - The flexible fibreoptic rhinolaryngoscope. AB - An accurate, reliable, inexpensive and safe method for the examination of the upper aero-digestive tract is described. Its efficacy is evaluated retrospectively on 250 patients over an 18-month period. PMID- 4020274 TI - Flexible fibreoptic rhinolaryngoscopy. Results of 338 consecutive examinations. AB - Flexible fibreoptic rhinolaryngoscopy has been shown to be an accurate, reliable, inexpensive and safe method of examining the upper aero-digestive tract (Lancer and Moir, 1985). The results of 338 consecutive examinations are reported. PMID- 4020275 TI - Fibre optic guided nasal intubation--shouldn't we be the experts? AB - Difficult intubations are more common in otolaryngological practice than any other branch of medicine or surgery. The majority of these are predictable. It is the unexpected intubational failure, usually in a patient undergoing treatment for an unrelated problem, that results in tragedy. In this paper the indications for fibre optic guided intubation are discussed, and the technique described and illustrated in a case of pharyngeal obstruction secondary to an epiglottic cyst. It is suggested that our expertise to operate within the upper airway should be exploited to the advantage of our patients, and of our anaesthetic and surgical colleagues. PMID- 4020276 TI - The role of fibreoptic nasopharyngoscopy in nasopharyngeal carcinoma (NPC). AB - With the introduction of the flexible fibreoptic nasopharyngo-laryngoscope, we have a sophisticated instrument for examination of the nasopharynx and larynx. It is also useful for obtaining biopsies from the nasopharynx and has many advantages over other methods. The most important is that it is possible to take biopsies from selected sites under direct visualization and the biopsy results are therefore more reliable. PMID- 4020277 TI - The role of fibreoptic oesophagogastroscopy in E.N.T. practice. AB - Fibreoptic endoscopy has only recently become used as a diagnostic tool for the E.N.T. surgeon but it has not been widely used in the investigation of pharyngeal disease. During a two-year period at Warwick Hospital 53 patients have undergone flexible fibreoptic endoscopy using a gastroscope, with visualization of the pharynx, larynx and upper G.I. tract as far as the duodenum. This report describes the technique employed, details the endoscopic findings in 53 patients, and discusses the indications for the technique and the advantages that it holds for the E.N.T. surgeon in the diagnosis and management of pharyngeal disease. PMID- 4020278 TI - The out-patient use of the fibrebronchoscope for examining the larynx. AB - The fibrebronchoscope has been used as a routine out-patient instrument, in 816 cases using 2 1/2 per cent cocaine anaesthesia without mishap, the suction channel making it ideal for clearing the thick post-irradiation secretions often seen in our joint clinic with radiotherapy. Patient tolerance has been excellent, many preferring it to mirror examination. I personally prefer the added length of the bronchoscope to the shorter nasopharyngoscope, allowing me not to be so close to the patient and also allowing me to let them see their own larynx and be reassured. The suction channel on the bronchoscope is a great advantage compared with the nasopharyngoscope. Video link-up is easily organized. Finally, as most District General Hospitals possess a fibrebronchoscope, it is something that can be organized with minimal or no cost. PMID- 4020279 TI - Strobofibrescopic colour video recording of vocal fold vibration. AB - We have designed a system for strobofibrescopic video recordings of vocal fold vibration. The system consists of a flexible laryngofibrescope, an improved model of laryngo-stroboscope, a colour video-camera, a video printer, a video-recorder and a TV monitor set. This system is applicable to most patients, even to children and those patients whose larynx is difficult to visualize. PMID- 4020280 TI - Laryngostroboscopic observations by means of inferior glottoscopy. PMID- 4020281 TI - Benign necrotizing osteitis of the external auditory meatus. PMID- 4020282 TI - A benign middle-ear adenoma producing facial paralysis. PMID- 4020283 TI - Polypoid lymphangioma of the tonsil: report of two cases and review of the literature. AB - Benign tumours of the tonsils are uncommon. Among them, lymphangiomas are rare, and only six well-documented cases have been previously reported. We present two additional cases with review of the literature. PMID- 4020284 TI - The learning disabled child: a retrospective review. PMID- 4020285 TI - A multi-option program for learning basic addition facts: case studies and an experimental report. PMID- 4020286 TI - Cognitive strategies of children with reading disability and normal readers in visual sequential memory. PMID- 4020287 TI - Conservation and mathematics achievement in the learning disabled child. PMID- 4020288 TI - The relationship of perceptual-motor development to learning readiness in kindergarten: a multivariate analysis. PMID- 4020289 TI - Prior history of learning disabilities in Reye's syndrome survivors. PMID- 4020290 TI - The kids-in-between: some solutions. PMID- 4020291 TI - A mainstreaming program that really works. PMID- 4020292 TI - Adapting teacher-made tests for mainstreamed students. PMID- 4020293 TI - Heterogeneity of dog interstitial fluid (peripheral lymph) high density lipoproteins: implications for a role in reverse cholesterol transport. AB - The heterogeneity of dog interstitial fluid (peripheral lymph) high density lipoprotein (HDL) was investigated and compared to plasma HDL. Interstitial fluid and plasma HDL of normal and cholesterol-fed dogs was subfractionated by ultracentrifugation and affinity and molecular weight sieving chromatography. Both plasma (P) and interstitial fluid (L) HDL can be subfractionated into a larger fraction (P-I and L-I) and a smaller one (P-II and L-II). Cholesterol feeding induces a large increase in the P-I and L-I component of HDL, but the increase in L-I is far greater in proportion than that of P-I. Furthermore, L-I of cholesterol-fed dogs appears to be almost exclusively discoid in shape, while only approximately 15% of particles in P-I are discoidal. The discoid HDL of L-I is reflected in its chemical composition: 28% unesterified cholesterol, 6% cholesteryl ester, 45% phospholipid, and 21% protein. It contains large amounts of apoE in addition to apoA-I and apoA-IV. We found that the association of apoE with discoid particles is frequent, but not necessary. Calculations based on known protein mass and quantitation of discoid particles on electron micrographs suggest that the concentration of discoid particles in the peripheral lymph of cholesterol-fed dogs is about fourfold that of the plasma of the same animal. These findings provide strong circumstantial evidence for the peripheral formation of discoid HDL, perhaps as an early event in reverse cholesterol transport. PMID- 4020294 TI - Inhibitory effects of C apolipoproteins from rats and humans on the uptake of triglyceride-rich lipoproteins and their remnants by the perfused rat liver. AB - Like rat C apolipoproteins, each of the C apolipoproteins from human blood plasma (C-I, C-II, C-III-1, and C-III-2) bound to small chylomicrons from mesenteric lymph of estradiol-treated rats and inhibited their uptake by the isolated perfused rat liver. This inhibitory effect of the C apolipoproteins was independent of apolipoprotein E, which is present only in trace amounts in these chylomicrons. Addition of rat apolipoprotein E to small chylomicrons from mesenteric lymph of normal rats did not displace C apolipoproteins and had no effect on the uptake of these particles by the perfused liver, indicating that an increased ratio of E apolipoproteins to C apolipoproteins on chylomicron particles, unaccompanied by depletion of the latter, may not promote recognition by the chylomicron remnant receptor. The hepatic uptake of remnants of rat hepatic very low density lipoproteins (VLDL) and small chylomicrons, which had been produced in functionally eviscerated rats, was also inhibited by addition of C apolipoproteins. These observations are consistent with the hypothesis that the addition of all of the C apolipoproteins to newly secreted chylomicrons and VLDL inhibits premature uptake of these particles by the liver and that depletion of all of these apolipoproteins from remnant particles facilitates their hepatic uptake. Remnants of chylomicrons and VLDL incubated with rat C apolipoproteins efficiently took up C-III apolipoproteins, but not apolipoprotein C-II (the activator protein for lipoprotein lipase). Preferential loss of apolipoprotein C II during remnant formation may regulate the termination of triglyceride hydrolysis prior to complete removal of triglycerides from chylomicrons and VLDL. PMID- 4020295 TI - Studies of low density lipoprotein molecular weight in human beings with coronary artery disease. AB - Low density lipoprotein molecular weight (LDL MW) correlates positively with coronary artery disease in cholesterol-fed nonhuman primates. To evaluate this in human beings with coronary artery disease (CAD) we measured LDL MW in 93 volunteers undergoing coronary angiography (47 controls and 46 CAD patients). LDL MW of CAD patients was less than that of controls (patients, 2.79 +/- 0.17 g/mumol; controls, 2.93 +/- 0.19 g/mumol; P less than 0.001). However, LDL MW decreased as plasma triglyceride increased and concentrations of triglyceride were greater in CAD patients than in controls. Since decreased LDL MW is likely to result, in part, from increased plasma triglyceride concentrations, we attempted to determine the effect of triglyceride on the relation of LDL MW to CAD in this study. After covariance adjustment for triglyceride, there was no LDL MW difference between CAD patients and controls. Because LDL heterogeneity has been identified in other studies and was apparent on inspection of agarose column profiles of LDL of these volunteers, we sought differences in the profiles that might distinguish coronary disease cases from controls. No differences could be found. In addition, we used density gradient ultracentrifugation to characterize LDL in more detail in a subset of volunteers who had a wide range of plasma triglyceride concentrations (50 mg/dl to 900 mg/dl). LDL mean hydrated density was inversely related to LDL MW and increased as triglyceride increased. The increase in peak density was reflected in an increase in percent of total protein in LDL found to have d greater than 1.045 g/ml and a decrease in protein in LDL of d 1.035-1.040 g/ml. These interrelationships were not apparently influenced by coronary artery status. PMID- 4020296 TI - Excretion of cholate glucuronide. AB - [3-3H]Cholic acid glucuronide [7 alpha,12 alpha-dihydroxy-3 alpha-O-(beta-D glucopyranosyluronate)-5 beta- cholan-24-oate] was synthesized and administered to rats prepared with either an external biliary fistula or a ligated bile duct. When bile fistula animals were given either microgram or milligram amounts of the glucuronide, biliary secretion of label was rapid and efficient: greater than 90% of the administered label was secreted within 60 min and total recovery of label in bile was 98.6 +/- 1.2%. Studies in which [14C]taurocholate was included in the dose indicated that this bile acid was secreted into bile significantly more rapidly than was the glucuronide. In animals with ligated bile ducts, urinary excretion was the major route of elimination: after 20 hr, 83.4 +/- 9.3% of the administered dose had been excreted in urine. Urinary excretion of cholate glucuronide was significantly more rapid than that of taurocholate. Gas-liquid chromatographic analysis of the methyl ester acetate derivatives of labeled compounds isolated from bile and urine by chromatography established that the bulk (greater than 70%) of the administered material was secreted in bile or excreted in urine as the intact cholate glucuronide. From these results, we conclude that the glucuronidation of cholic acid produces a derivative which is rapidly and effectively cleared from the circulation and excreted. PMID- 4020297 TI - Biosynthesis of neutral glycosphingolipids in kidney slices from male and female mice. AB - Previous reports from our laboratory (1981. J. Biol. Chem. 256: 13112-13120 and 1983. Endocrinology. 113: 251-258) showed the absence of Nfa-GalCer and Nfa GaOse2Cer in kidneys of several strains of female mice. These lipids are always present in male kidneys and several other glycolipids are also elevated in males. To test whether this phenomenon is due to lowered biosynthesis in females, glycosphingolipid formation was assessed in kidney slices with [3H]galactose as precursor. The glycolipids were extracted after various incubation periods (from 30 min to 90 min) and individual glycolipids were separated and quantitated by high performance liquid chromatography and radioactivity was determined. The rate of formation of hydroxy fatty acid-containing galactosylceramide was the same in both sexes. The glycolipids which were low or not detectable in female kidney, Nfa-GalCer, Nfa-GaOse2Cer and Hfa-GaOse2Cer were rapidly labeled in the male kidney slices. These results suggest that nonhydroxy fatty acid-containing ceramide:UDP-Gal galactosyltransferase and hydroxy fatty acid-containing galactosylceramide:UDP-Gal galactosyltransferase have elevated activities in males. While the glucosylceramides are labeled at the same rates in both sexes, lactosylceramide appears to be labeled at higher rates in the male tissue. This suggests that glucosylceramide:UDP-Gal galactosyltransferase also has elevated activity in males. In addition, these data show that monohexosylceramides with different ceramide compositions are labeled at different rates. PMID- 4020298 TI - Membrane cholesterol and phospholipid in consecutive concentric sections of human lenses. AB - Lens membrane preparations have been shown to have a remarkable rigidity which increases in the inner nuclear region of the lens and has been correlated with the cholesterol (C)/phospholipid (PL) ratio. However, the distribution of these lipids in single lenses had not been determined. Utilizing a new technique for isolating consecutive layers of a human lens, lipid composition and contents of seven pairs of normal lenses from subjects ranging from 54 to 77 years old have been analyzed. It was found that the PL content remains relatively constant at 22 24 micrograms/mg through all but the nuclear 10-15% of the lens dry weight where it drops precipitously to about 7 micrograms/mg. The C distribution is more complex; the C content is at a low level of 14 micrograms/mg in the outer cortical 15-20%, rises to 25 micrograms/mg in the inner cortical 40-60% of the total lens weight, and drops to 12 micrograms/mg upon reaching the nucleus. Thus, the continuous increase in the lens C/PL ratio is due to the increase in C in the cortex and the large decrease in PL in the nucleus. Analyses of phospholipid and fatty acid composition in the different regions of the lens indicate significant differences. However, the abundance of mono-unsaturated fatty acids contributing to the rigidity of the membrane has only minor variation. The lens has a remarkably low overall lipid content of 4% and only 2% in the nuclear region. Calculation of the surface area of the nuclear fiber cell suggests that less than one-third of the membrane is made of PL bilayer. Thus, a mosaic of PL and C patches or some other type of structure involving membrane fusion must be present. Conversion of the % dry weight occupied by the concentric fiber fractions to their location on the lens axis in mm indicates that the nuclear 15% dry weight of the tissue occupies more than 50% of the axial length. This region contains the embryonic lens and the primary lens fibers. Similarly, the metabolically active outer 20% of the dry weight accounts for less than 10% of the visual axial length and contains cells undergoing terminal differentiation. Cataractous lenses have lipid distributions similar to those of the normal lenses suggesting that membrane lipid is either not involved in cataract formation or that the primary insult is localized in an undetectable small number of fiber cells. PMID- 4020299 TI - Phosphatidylserine decarboxylase from Clostridium butyricum. AB - Phosphatidylserine decarboxylase activity has been characterized in membrane preparations from Clostridium butyricum ATCC 19398. A particulate fraction was shown to catalyze the formation of phosphatidylethanolamine and plasmenylethanolamine when vesicles containing phosphatidylserine and plasmenylserine were used as substrate. No plasmenylethanolamine was formed when phosphatidylserine alone was used as substrate. The activity with phosphatidylserine was activated by divalent cations and was optimal under anaerobic conditions. Ionic detergents inhibited phosphatidylethanolamine formation strongly and nonionic detergents inhibited partially. In the presence of Triton X-100, phosphate from [32P]phosphatidylserine appeared in three unidentified lipid products, in addition to phosphatidylethanolamine. The formation of these products was time- and Triton X-100 concentration-dependent. Hydroxylamine inhibited phosphatidylserine decarboxylase, but did not prevent the reactions stimulated by Triton X-100. PMID- 4020300 TI - Activities of serine palmitoyltransferase (3-ketosphinganine synthase) in microsomes from different rat tissues. AB - Serine palmitoyltransferase [EC 2.3.1.50] catalyzes the first unique reaction of sphingolipid biosynthesis. To determine whether or not different rat tissues are capable of initiating this pathway, its activity was determined for microsomes from rat liver, lung, brain, kidney, intestine, spleen, muscle, heart, pancreas, testes, ovary, and stomach. Serine palmitoyltransferase was found in every tissue, and, when compared to the microsomal glycerol 3-phosphate acyltransferase, the activities correlated directly with their sphingomyelin levels as a percentage of total phospholipids. This suggests that the activities were comparable to expected cellular needs for long-chain bases, if the initial enzymes of glycerolipid and sphingolipid biosynthesis influence the phospholipid composition of cells by determining the relative partitioning of fatty acyl-CoA's toward these two lipid classes. Serine palmitoyltransferase activities were also determined using different fatty acyl-CoA's and were consistently greatest with CoA thioesters of saturated fatty acids with 16 +/- 1 carbon atoms. This suggests that the predominance of 18-carbon long-chain bases in vivo is due to the higher activity of this enzyme with palmitoyl-CoA. Together, these findings indicate a role for serine palmitoyltransferase in regulating both the type and amount of long-chain bases found in tissues. PMID- 4020301 TI - Synthesis of phosphatidylcholine analogs with an alkyl group at C1 or C3 of the glycerol moiety. AB - The syntheses of 1,2-di-(O-hexadecyl)-rac-glycero-3-phosphocholines containing a methyl group at either C1 or C3 of the glycerol moiety are described. The methyl group was introduced at C1 in a synthetic scheme beginning with the hydroxylation of methyl vinyl ketone. The primary hydroxyl was protected by tritylation and the carbonyl group was reduced with sodium borohydride. Di-O-alkylation with 1 bromohexadecane was accomplished using finely powdered potassium hydroxide in refluxing toluene. Detritylation afforded two diastereomers of 2,3-di-(1 hexadecyloxy)butanol. Reaction with the simple phosphorylating agent, dimethylphosphoryl chloride (Bittman, R., A. F. Rosenthal, and L. A. Vargas. 1984. Chem. Phys. Lipids. 34: 201-205), followed by conversion to the phosphatidic acid and condensation with choline tosylate in the presence of trichloroacetonitrile afforded the diastereomers of 1-methyl-1,2-di-(O-hexadecyl) rac-glycero-3-phosphocholine. The analog bearing a methyl group at C3 was prepared in a synthetic scheme beginning with the hydroxylation of acrolein dimethyl acetal. After di-O-alkylation with 1-bromohexadecane and sodium hydride in dimethyl sulfoxide/toluene, the acetal was converted to the aldehyde. Reaction with methylmagnesium bromide afforded the diastereomers of 1,2-di-(1 hexadecyloxy)-3-butanol, which were converted to the phosphocholine derivatives. These diether phosphatidylcholine analogs may be useful for investigating the effect of steric bulk at C1 and C3 of the glycerol moiety on the interactions with membrane components. PMID- 4020302 TI - Semi-synthetic approach for the preparation of homogeneous plasmenylethanolamine utilizing phospholipase D from Streptomyces chromofuscus. AB - A simple method for the preparation of homogeneous molecular species of plasmenylcholine and plasmenylethanolamine was developed. The method utilized reverse phase high performance liquid chromatography to isolate homogeneous molecular species of plasmenylcholine prepared by acylation of lysoplasmenylcholine. Plasmenylcholine was directly converted to plasmenylethanolamine by transphosphatidylation utilizing phospholipase D from Streptomyces chromofuscus. This method permits the facile labeling of homogeneous molecular species of plasmalogens in the polar head group, the sn-2 acyl chain, or both, for the first time. PMID- 4020303 TI - Isolation and purification of cardiolipin from beef heart. AB - A simple and efficient procedure is described for the preparation of cardiolipin sodium salt from beef heart. A crude phospholipid fraction is isolated by chloroform-methanol extraction of the homogenized tissue, followed by acetone precipitation and reprecipitation in 4% aqueous CaCl2-methanol. Cardiolipin is separated from the calcium salts of the acidic phospholipids by partition column chromatography on silica gel (Polygosil 60-63100) using 2-propanol-cyclohexane water 50:43:7 (v/v/v) as eluent. Further purification of the cardiolipin is achieved by high performance liquid chromatography of the calcium salt on silica gel (Lichrosorb Si 60-5) with a neutral eluent (2-propanol-cyclohexane-water 45:50:5 (v/v/v], followed by quantitative conversion to the sodium salt. The yield of this procedure is 1.5-2.1 g of pure 99% sodium salt of cardiolipin per kg of moist ventricular tissue. PMID- 4020305 TI - Global asymptotic stability of the size distribution in probabilistic models of the cell cycle. AB - Probabilistic models of the cell cycle maintain that cell generation time is a random variable given by some distribution function, and that the probability of cell division per unit time is a function only of cell age (and not, for instance, of cell size). Given the probability density, f(t), for time spent in the random compartment of the cell cycle, we derive a recursion relation for psi n(x), the probability density for cell size at birth in a sample of cells in generation n. For the case of exponential growth of cells, the recursion relation has no steady-state solution. For the case of linear cell growth, we show that there exists a unique, globally asymptotically stable, steady-state birth size distribution, psi*(x). For the special case of the transition probability model, we display psi*(x) explicitly. PMID- 4020304 TI - A symmetric two locus model with viability and fertility selection. AB - A two locus deterministic population genetic model is analysed. One locus is under viability selection, the other under fertility selection with both forms of selection completely symmetric. It is shown that linkage equilibrium may occur at two different equilibrium points. For a two-locus polymorphism to be stable, it is necessary that the viability locus be overdominant but not necessary that the fertility locus, considered separately, be able to support a stable polymorphism. The overlaps in stability are not as complex as under two locus symmetric fertilities, but considerably more complex than with symmetric viabilities. Extensions of the analysis for the central linkage equilibrium point with multiple viability and fertility loci are indicated. PMID- 4020306 TI - Evaluation of radionuclide scintigraphy in intracranial abscess. PMID- 4020307 TI - Computed tomography in the diagnosis of orbital lesions. PMID- 4020309 TI - Adult respiratory distress syndrome associated with antacid aspiration: a case report. PMID- 4020308 TI - Tuberculous myocarditis: a report of two cases. PMID- 4020310 TI - Toxic shock syndrome, a case report in childhood. PMID- 4020311 TI - Antioestrogen inhibition of oestradiol-induced alterations in hypothalamic noradrenaline turnover. AB - Long-term (4-6 weeks) ovariectomized rats were injected with either oestradiol benzoate (OB; 20 micrograms s.c.) or monohydroxytamoxifen (MTAM; 0.2 mg i.p.) plus OB. Oestradiol benzoate was administered at 12.00 h on day 0 and MTAM was given immediately before OB, followed by further injections twice daily to maintain sufficiently high antioestrogen levels. When given alone, OB reduced the serum levels of LH during the morning (08.00-09.00 h) and afternoon (17.30-18.30 h) hours of day 3 after priming. The feedback actions of OB on LH release were accompanied by time-dependent alterations of noradrenaline turnover in the preoptic-anterior hypothalamic brain area (POAH). On day 3 after priming the noradrenaline turnover rate was reduced in the morning and increased in the afternoon. The increase correlated with an enhanced sensitivity of the LH secretory system to progesterone. The antioestrogen MTAM blocked the OB-induced sensitization of LH release to the stimulatory action of progesterone and interfered with the stimulatory long-term effect of oestradiol on hypothalamic noradrenaline turnover. The data strongly support the view that the oestrogen induced afternoon increase of noradrenaline turnover in the POAH represents a prerequisite for the induction of LH surges. The stimulatory effect of oestradiol on hypothalamic noradrenaline turnover seems to be mediated by a classical oestrogen receptor mechanism. PMID- 4020312 TI - Precocious ovulation induced by human chorionic gonadotrophin in the immature female rat: comparison of follicle growth induced by treatment with human chorionic gonadotrophin and by electrical stimulation of the hypothalamus. AB - Precocious first ovulation, preceded by an endogenous preovulatory LH surge, could be predictably induced in immature female rats by administering repeated injections of human chorionic gonadotrophin (hCG). Administration of a dose of 0.05-0.075 i.u. hCG, four times a day from day 28 to day 31 of age resulted in a highly constant ovulatory response: at 4.0 +/- 0.0 days after the start of treatment 7.7 +/- 0.3 (n = 15) ova were found. Use of a higher dose of hCG (0.1 i.u.) resulted in lower numbers of ova (5.6 +/- 0.4, n = 7; P less than 0.005) whereas use of a lower dose of hCG (0.025-0.038 i.u.) resulted in a less constant timing of the induced ovulation at 5.4 +/- 0.2 days after the start of treatment (n = 7; P less than 0.0005). In animals treated with the dose of 0.05-0.075 i.u. hCG, a positive correlation was found between body weight at the start of treatment and the number of ova released (r = 0.75, n = 25; P less than 0.001). Ovarian follicle dynamics were studied on the various days of hCG treatment (dose 0.05-0.075 i.u.) and compared with the follicle changes that take place after electrical stimulation of the hypothalamus, performed on day 28, a treatment known to result in first ovulation 4-5 days later. In both groups a decrease in the number of the smallest and the middle-sized antral follicles as compared with their respective controls was seen, whereas numbers of follicles in the largest, 'ovulatable' size classes gradually increased.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4020313 TI - Induction of ovulation in vitro in the hen: dependency of the response to LH on age and rate of lay. AB - Two experiments were conducted on White Leghorn hens to investigate the effect of different concentrations of LH on the frequency of induction of ovulation in vitro of ovarian follicles collected 18-20 h before the expected time of ovulation from birds of three different ages (7, 18 and 30 months) or of the same age but laying short (three to four) or long (more than seven) sequences of eggs. The ability of LH to induce ovulation was directly related to the age of the donors of the follicles. Follicles derived from hens laying short sequences of eggs were less responsive to the ovulation-inducing effects of LH than were follicles from birds laying long sequences. These observations suggest that the sensitivity of ovarian follicles to the ovulation-inducing effects of LH declines with age and is greater in hens laying long sequences of eggs than those laying short sequences. PMID- 4020314 TI - The role of neonatal and pubertal gonadal hormones in regulating the sex dependence of the hepatic microsomal testosterone 5-reductase activity in the rat. AB - Heptic microsomal testosterone 5-reductase activity was approximately fourfold higher in adult female rats than in males. This discrepancy was only partly androgen-dependent since gonadectomy of male rats at 68 days of age resulted in only a partial increase of the enzyme activity. This increase was reversible by the administration of testosterone. Similar treatment, however, produced no effect in the female rat, indicating that there is a sex difference in testosterone responsivity. Castration of newborn male rats resulted in a marked increase in the basal enzyme activity. This increase was not affected by treating the adults with testosterone. Giving testosterone to male rats immediately after neonatal gonadectomy, or to newborn female rats, did not produce the male pattern of both the basal enzyme activity and the testosterone responsivity in adulthood. These results suggest that a brief exposure to neonatal androgen is not critical for the expression of the male type of enzyme activity, but that the continuous presence of the male gonads up to and including the pubertal period is essential. Exposure of pubescent female rats to testosterone during the period from 35 to 50 days of age resulted in a significant increase in testosterone sensitivity when tested at 90 days of age, suggesting that pubertal exposure to androgen is important for the expression of testosterone responsivity in adulthood. The sensitivity was potentiated when the animals were ovariectomized before puberty. Furthermore, the enzyme activity in prepubertally ovariectomized female rats was significantly lower than that in adult gonadectomized animals.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4020315 TI - Iodothyronine kinetics in the rabbit: an experimental model. AB - Turnover studies of thyroxine (T4), 3,5,3'-tri-iodothyronine (T3) and 3,3',5'-tri iodothyronine (rT3) have been performed in the rabbit. A novel modification of a conventional radioimmunoassay has been used to measure specific 125I-labelled iodothyronines in small volumes of plasma in the presence of other 125I-labelled metabolites. Kinetic analysis of plasma disappearance of tracer was performed by a new theoretical approach. For T4 the mean (+/- S.D.) plasma concentration, clearance and production rates were 34 +/- 12 nmol/l, 109 +/- 19 ml/kg per day and 3.7 +/- 1.4 nmol/kg per day respectively (n = 9). For T3 the corresponding values were 2.04 +/- 0.42 nmol/l, 1.52 +/- 0.29 litres/kg per day and 3.07 +/- 0.76 nmol/kg per day (n = 8), and for rT3 0.12 +/- 0.04 nmol/l, 5.7 +/- 1.7 litres/kg per day and 0.69 +/- 0.23 nmol/kg per day (n = 8). The combination of these two new methodologies affords a simple and convenient means of studying iodothyronine metabolism under normal and abnormal conditions. The techniques employed may be generally applied to turnover studies of other compounds of physiological interest which can be measured by radioimmunoassay. PMID- 4020316 TI - Age, sex and gonadal influences on oestrogen receptor content in the rat liver. AB - Liver cytosol oestrogen receptor (OR) content of intact and gonadectomized male and female rats of defined age (1-18 months) was measured by the controlled pore glass bead assay. The OR content of animals of both sexes aged 3 weeks was low to insignificant (0.12 +/- 0.04 (S.E.M.) pmol/g wet wt liver). In the intact animal, liver OR reached maximum levels at an earlier age in the male (1.35 +/- 0.12 pmol/g at 28-32 weeks) than in the female (4.89 +/- 0.17 pmol/g at 44-52 weeks). In the mature female the OR is thus maintained at a level threefold greater than in males of comparable age. Levels of OR in the gonadectomized male tended to be higher, at all ages, than those in the intact male but this difference was not statistically significant. Ovariectomy was associated with a decreased OR content in rats aged less than 6 months and an increase in the older rats, but these effects (of ovariectomy) were not statistically significant. In the females, regression analysis of pooled data, combining all ages, indicated a significant positive correlation between OR and liver wet weight, independent of gonadal status; no such relationship was found with the males. The results indicate that factors influencing liver cytosol OR content include maturity, age and sex whereas the gonads have little obvious effect. These findings lend further support to the concept that sex differences exist in the liver. PMID- 4020317 TI - Cortisol is natriuretic in the immature ovine fetus. AB - Cortisol was infused, intravenously, for 4 h continuously into 5 chronically cannulated ovine fetuses at 111-120 days of gestation (term is 142-152 days). The dose used was 100 micrograms/h, and raised fetal blood cortisol concentrations from 8.2 +/- 4.0 to 56.5 +/- 19.0 nmol/l (values are mean +/- SEM). The effects observed were a 4-5 fold increase in sodium and chloride excretion, a doubling of potassium excretion and free water clearance, no significant changes in urine pH, urea and creatinine excretions, and an increase in urine osmolality from 129 +/- 7.5 to 154.4 +/- 11.3 mosmol/kg water. There were no significant changes in any of the measured parameters in 5 fetuses infused with 0.9% NaCl for 4h. It is suggested that the hyponatremia and inability to retain sodium observed in many premature or very low birth weight babies may be due to the fact that their kidneys are behaving as fetal rather than neonatal organs and responding to the high plasma cortisol concentrations found in such babies with a natriuresis. PMID- 4020318 TI - Prolactin permits the expression of a circadian variation in insulin receptor profile in hepatocytes of the golden hamster (Mesocricetus auratus). AB - Insulin receptor profile was determined in freshly isolated hamster hepatocytes at two times (07.00 and 16.00 h) during a 14-h daily photoperiod (08.00-22.00 h). The hamsters were pretreated for 5 days with bromocriptine (to inhibit prolactin release), bromocriptine and prolactin replacement, or control saline injections. The insulin receptor profile was determined by Scatchard plot analysis. The insulin receptor number (high and low affinity) was three times greater at 07.00 than at 16.00 h among saline-injected controls. However, their affinities did not differ. Bromocriptine pretreatment reduced (70%) both the high and low affinity receptor numbers and increased the affinity of the high affinity receptor at 07.00 h. Prolactin replacement in bromocriptine-treated hamsters restored the receptor profile at 07.00 h to control values. These data indicate that prolactin facilitates the expression of a circadian variation in insulin receptor profile. PMID- 4020319 TI - Naloxone-induced secretion of LH in the male Syrian hamster: modulation by photoperiod and gonadal steroids. AB - The role of endogenous opiates in the regulation of photoperiodically induced testicular regression was studied in the male Syrian hamster. In reproductively active hamsters exposed to a long photoperiod (LD; 16 h light: 8 h darkness) or to short days (SD; 8 h light: 16 h darkness) for 20 weeks or to SD after pinealectomy, administration of naloxone, a competitive opiate receptor antagonist, at doses of 2.5-20 mg/kg, significantly increased serum LH concentrations. In marked contrast, these doses of naloxone did not produce any change in LH levels in reproductively quiescent hamsters exposed to SD for 8 weeks. The influence of gonadal steroids on the LH response to naloxone was studied in hamsters castrated or castrated and implanted s.c with a capsule containing testosterone. Naloxone did not induce LH release in castrated hamsters maintained in LD or in SD, but this response was restored in LD but not SD when serum testosterone concentrations were maintained at levels similar to those observed in intact reproductively active hamsters. These results show that inhibition of reproduction by the photoperiod prevents naloxone-induced LH release in the male hamster. This lack of response to naloxone is not due, however, to the lower testosterone titres present in these animals compared with reproductively active animals. Responsiveness to naloxone can be restored when the animal is rendered insensitive to the inhibitory photoperiod either by removal of the pineal gland or by induction of photorefractoriness by extended exposure to SD. PMID- 4020320 TI - Human observing: maintained by negative informative stimuli only if correlated with improvement in response efficiency. AB - Two experiments investigated the effect of observing responses that enabled college students to emit more efficient distributions of reinforced responses. In Experiment 1, the gains of response efficiency enabled by observing were minimized through use of identical low-effort response requirements in two alternating variable-interval schedules. These comprised a mixed schedule of reinforcement; they differed in the number of money-backed points per reinforcer. In each of three choices between two stimuli that varied in their correlation with the variable-interval schedules, the results showed that subjects preferred stimuli that were correlated with the larger average amount of reinforcement. This is consistent with a conditioned-reinforcement hypothesis. Negative informative stimuli--that is, stimuli correlated with the smaller of two rewards- did not maintain as much observing as stimuli that were uncorrelated with amount of reward. In Experiment 2, savings in effort made possible by producing S- were varied within subjects by alternately removing and reinstating the response reinforcement contingency in a mixed variable-interval/extinction schedule of reinforcement. Preference for an uncorrelated stimulus compared to a negative informative stimulus (S-) decreased for each of six subjects, and usually reversed when observing permitted a more efficient temporal distribution of the responses required for reinforcement; in this case, the responses were pulls on a relatively high-effort plunger. When observing the S- could not improve response efficiency, subjects again chose the control stimulus. All of these results were inconsistent with the uncertainty-reduction hypothesis. PMID- 4020321 TI - Control of responding by the location of sound: role of binaural cues. AB - In auditory localization experiments, where the subject observes from a fixed position, both relative sound intensity and arrival time at the two ears determine the extent of localization performance. The present experiment investigated the role of binaural cues in a different context, the sound-position discrimination task, where the subject is free to move and interact with the sound source. The role of binaural cues was investigated in rats by producing an interaural imbalance through unilateral removal of the middle auditory ossicle (incus) prior to discrimination training. Discrete trial go-right/go-left sound position discrimination of unilaterally incudectomised rats was then compared with that of normal rats and of rats with the incus of both sides removed. While bilateral incus removal affected binaural intensity and arrival times, the symmetry of sound input between the two ears was preserved. Percentage of correct responses and videotaped observations of sound approach and exploration showed that the unilateral rats failed to localize the sounding speaker. Rats with symmetrical binaural input (normal and bilaterally incudectomised rats) accurately discriminated sound position for the duration of the experiment. Previously reported monaural localization based upon following the intensity gradient to the sound source was not observed in the unilaterally incudectomised rats of the present experiment. It is concluded that sound-position discrimination depends upon the use of binaural cues. PMID- 4020322 TI - Probability and delay of reinforcement as factors in discrete-trial choice. AB - Pigeons chose between two alternatives that differed in the probability of reinforcement and the delay to reinforcement. A peck on the red key always produced a delay of 5 s and then a possible reinforcer. The probability of reinforcement for responding on this key varied from .05 to 1.0 in different conditions. A response on the green key produced a delay of adjustable duration and then a possible reinforcer, with the probability of reinforcement ranging from .25 to 1.0 in different conditions. The green-key delay was increased or decreased many times per session, depending on a subject's previous choices. The purpose of these adjustments was to estimate an indifference point, or a delay that resulted in a subject's choosing each alternative about equally often. In conditions where the probability of reinforcement was five times higher on the green key, the green-key delay averaged about 12 s at the indifference point. In conditions where the probability of reinforcement was twice as high on the green key, the green-key delay at the indifference point was about 8 s with high probabilities and about 6 s with low probabilities. An analysis based on these results and those from studies on delay of reinforcement suggests that pigeons' choices are relatively insensitive to variations in the probability of reinforcement between .2 and 1.0, but quite sensitive to variations in probability between .2 and 0. PMID- 4020324 TI - Cellular processing of bovine factors X and Xa by cultured bovine aortic endothelial cells. AB - Previous studies have shown that Factor X and Factor Xa bind specifically to distinct sites on the endothelial cell surface. Since the coagulant activity of a cell-bound clotting protein is dependent on its remaining on the cell surface, endocytosis and degradation studies have been carried out. Cell-bound Factor X was internalized at 0.07 fmol/min/10(6) cells, a rate slower than its dissociation from the cell surface. Endocytosed Factor X was not degraded, but was returned to the cell surface. In contrast, Factor Xa was internalized at an initial rate of 0.38 fmol/min/10(6) cells and subsequently degraded at about the same rate. The degradation of Factor Xa was prevented by chloroquine. These results suggest that Factor Xa is internalized and degraded by a lysosomal dependent pathway. Studies with Factor X- and Xa-colloidal gold conjugates showed endocytosis proceeding at coated pit regions, and accumulation of Factor Xa-gold particles in lysosome-like structures. Endocytosis was studied as a clearance pathway for cell-bound Factor Xa by activating Factor X with Factors IXa and VIII on the endothelial cell surface. Endocytosis of the Factor Xa formed was significant, as only 44% of the Factor Xa formed was released into the supernatant, whereas the remainder was internalized and degraded. Thus, endocytosis of Factor Xa bound to its specific endothelial cell sites may be an important factor in the balance of vessel wall hemostatic mechanisms. PMID- 4020325 TI - 3H-labelled RU 38486: characterization of binding sites in human uterine cytosol. AB - The behaviour of the antifertilizing synthetic steroid RU 38486 towards human uterine progestin receptor was investigated. RU 38486 competed in the same order of magnitude as progesterone for the [3H]R 5020 binding site of progestin receptor, whereas R 5020 was unable to compete against [3H]RU 38486. This apparent contradiction could be explained by means of HPLC-chromatography. HPLC chromatography with an anion exchange column (MonoQ, Pharmacia, Uppsala, Sweden) showed that [3H]RU 38486 forms at least two stable complexes with uterine cytosol, on one hand with serum albumin, which presents almost 90% of bound radioactivity, and on the other hand with the two native progestin receptor forms, corresponding to 4 S and 8 S receptor forms in sucrose density gradient analysis. Whether reduced binding of salt-activated RU 38486 receptor complexes to DNA-cellulose is due to reduced activation is still uncertain and remains to be further investigated. PMID- 4020323 TI - Chlordiazepoxide effects on ethanol self-administration: dependence on concurrent conditions. AB - Experiments examined the effects of acute doses of chlordiazepoxide upon ethanol self-administration in the rat. A concurrent-schedule procedure was used that employed choice between ethanol (5%) and a second fluid (either water or a 1% sucrose solution). When ethanol and water were the available fluids, chlordiazepoxide at doses of 15 and 20 mg/kg reduced ethanol-reinforced responding and intake, with a greater reduction occurring at the 20 mg/kg dose. However, when ethanol and sucrose were concurrently available, in many rats only the 20 mg/kg dose of chlordiazepoxide reduced ethanol-reinforced responding. The differences in dose response function occurred in most animals without large changes in the baseline ethanol-reinforced responding across the two concurrent conditions. Thus the dose-effect curve relating chlordiazepoxide and ethanol self administration can be altered, dependent upon the nature of the concurrently available reinforcers. PMID- 4020326 TI - The effect of storage at different temperatures on cholinesterase activity in human serum. AB - The effect of storage on the catalytic concentration of cholinesterase and on the reference values of cholinesterase in human serum were studied. When serum was stored at room temperature (20 degrees C), at 4 degrees C and at - 20 degrees C (one year) there was no change in catalytic activity. Even after nine times freezing and thawing (over nine weeks) the catalytic activity was unaffected. The average reference value was significantly higher for males than for females (3.11 +/- 0.57 vs 2.50 +/- 0.43 kU/l). PMID- 4020327 TI - [Mineral and trace elements in human urine]. AB - Mineral and trace elements (Al, B, Ca, Cu, Fe, K, Li, Mg, Na, P and Zn) in 24 hour human urine samples from approximately 100 healthy persons (age between 20 and 50 years) were analysed by ICP (Inductively Coupled Plasma) and DCP (Direct Current Plasma) emission spectroscopy. The obtained values can be taken as "reference values" owing to the large number of individual samples. Mean values and the range of substance concentrations and substance excretion per 24 hours are given. Physiological reference values are reported for Ba, Sr and Ti, which are of particular interest in the field of occupational medicine; examples of increases in these three elements as a result of exposure at the work place are also given. Additionally some average values for Cd, Co, Ni and Pb have been measured by a voltammetric technique. PMID- 4020328 TI - High performance liquid chromatographic procedure for the simultaneous determination of theophylline, caffeine, and phenobarbital in neonates. AB - A sensitive HPLC method is reported for the simultaneous determination of theophylline, caffeine, and phenobarbital in 100 microliters of plasma. After a single extraction of the drugs with chloroform/isopropanol (90 + 10 by volume) at low pH in the presence of an excess of ammonium sulphate they are resolved and quantified using a reversed-phase column (Spherisorb 5 ODS). The drugs are eluted with a binary-solvent gradient system (acetonitrile/phosphate buffer pH 4.6) at room temperature and monitored at 204 nm. Quantitation is based on peak-height ratio of analyte to interval standard (8-chlorotheophylline). Complete chromatographic resolution of all drugs is achieved within 15 min. The method is linear to 40 mg/l of theophylline and caffeine, and to 80 mg/l of phenobarbital. Numerous drugs and xanthine metabolites tested do not interfere. PMID- 4020330 TI - Human salivary arginase and its deficiency in argininaemia. AB - Arginase from normal human mixed saliva was characterized. The enzyme was completely activated after a preincubation of 20 min at 55 degrees C and a Mn2+ final concentration of 5 mmol/l. The pH optimum was 9.6-9.8, and the Km for L arginine was 4.2 +/- 0.7 mmol/l. In normal saliva only one form was found, which was chromatographically identical with the cationic form of arginase in liver and blood cells. Salivary arginase was completely precipitated by rabbit antiserum against human liver arginase. Arginase activity was not detectable in the saliva of patients suffering from argininaemia. Enzyme activities in the saliva of the heterozygous parents and the unaffected daughter were 0.08, 0.07 and 0.12 U/mg protein, respectively, whereas the activities in the saliva of 60 healthy adults and 8 children were 0.17 +/- 0.11 and 0.16 +/- 0.06 U/mg protein, respectively. PMID- 4020329 TI - [Statistical problems in comparative clinical chemical analysis. Report of the workshop conference of the German Society for Clinical Chemistry, 12 and 13 January 1984, Bremen]. AB - In continuation of the three previous workshops on this theme, the Passing-Bablok method was recapitulated and compared with standardized main component analysis. Participants in the workshop recommended both methods in place of the classical regression analysis. An essential advantage of the standardized main component is that it is more easily understood by the clinical chemist and his coworkers, and it involves fewer calculation steps. On the other hand, outliers must be recognized and eliminated, and certain other assumptions must be fulfilled. In comparison, the Passing-Bablok method is much more robust, but requires more calculation. The workshop also discussed unresolved questions concerning bases for the comparison of methods: the necessary number of samples, measures of scatter for description of precision, comparison of discrete results and several independent variances. These will be treated in greater depth in subsequent workshops. PMID- 4020331 TI - Preparation and control of ethylene glycol-stabilized haemolysates for glycated haemoglobin assay. AB - The preparation and evaluation of ethylene glycol-stabilized haemolysates for use as control material for the assay of glycated haemoglobins is described. These haemolysates were prepared from normal and diabetic blood samples by following the procedure normally used to purify human haemoglobin, with the addition of dialysis to remove glucose from the labile fractions, and dilution with ethylene glycol. All the haemoglobin fractions were converted into the carbon monoxide form to increase their stability and were stored under different conditions. During a 10 month period of storage at -20 degrees C no significant change in the glycated haemoglobins level was observed. PMID- 4020332 TI - International Federation of Clinical Chemistry (IFCC), Scientific Committee, Analytical Section. Quantities and units in clinical chemistry: Nebulizer and flame properties in flame emission and absorption spectrometry. PMID- 4020333 TI - Shaking chills and fever. PMID- 4020334 TI - Characteristics and management of febrile young children seen in a university family practice. AB - A cohort of 311 children registered with the University of Washington Family Medical Center was retrospectively identified and followed until the age of 2 years. Analysis of all encounters for which a temperature of 37.7 degrees C (100 degrees F) or above was noted revealed 438 such encounters among 189 patients. Only 30 encounters involved patients aged under 3 months, and in 74 percent of the encounters the temperature was below 38.9 degrees C (102 degrees F). The most common diagnoses were otitis media (34 percent), upper respiratory tract infection (19 percent), fever without a source (14 percent), and acute gastroenteritis (7 percent). While antibiotic usage, follow-up, and laboratory utilization all increased with increasing temperature, the latter was unrelated to a child's age. Laboratory evaluation of children considered at high risk for occult illness did not adhere to published guidelines. A more aggressive laboratory approach is recommended for such children, as is follow-up contact. Further studies to evaluate the risk of occult illnesses in febrile children seen in family medicine settings would be helpful in refining and improving management strategies in these settings. PMID- 4020335 TI - An assessment of the practice of preventive cardiology in an academic health center. AB - There is evidence that attention to cardiovascular risk factors will decrease the mortality of atherosclerotic disease. The objective of this study was to ascertain how often cardiovascular risk factors were assessed and modified in inpatients and newly seen outpatients aged 10 to 50 years at the University of Missouri-Columbia Hospital and Clinics. A total of 461 randomly selected inpatient and outpatient charts were reviewed from three departments: family practice, internal medicine, and pediatrics. Each record was assessed for history of smoking, exercise, diet, stress, and familial heart disease, for blood pressure measurement, and for serum lipid profile and glucose determination. With the exception of blood pressure, the risk factors were infrequently assessed in outpatients. Again excepting hypertension, there was little evidence of any attempt to modify those risk factors identified in inpatients or outpatients. Therefore, an educational program in risk factor recognition and modification is needed for primary care physicians. PMID- 4020336 TI - Styles of care provided to children in the United States: a comparison by physician specialty. AB - This study was based on findings from a national survey of physicians that was conducted from 1975 to 1977. The data concern face-to-face encounters with children in the ambulatory care setting. Over one half of the practices of pediatricians consisted of infants and preschoolers, whereas well over 50 percent of the child patients of other types of physicians were 10 to 19 years old. The proportion of visits dealing with a problem already under care was consistently greater for specialists other than primary care physicians; the proportion of visits for preventive care was much lower in the practices of these specialists than in primary care practice. These findings suggest that other specialists are functioning in ways different from primary care physicians. As compared with family physicians, pediatricians performed more diagnostic tests for all diagnoses and more immunizations and counseling about growth and development, were more likely to have seen children previously for problems other than the one dealt with in the visit under consideration, and were more likely to report that no specific therapy was required (except for well-child care). However, family physicians did more counseling about family and sex matters than pediatricians, were much more likely to have seen musculoskeletal and skin problems among 10- to 19-year-old patients, and were much more likely to have administered cauterization, cryotherapy, or suturing for skin problems. Family physicians provided more counseling of all types and did more minor surgical procedures than general practitioners. These and other findings show the existence of systematic differences across specialties in the care of children, even for apparently similar problems. PMID- 4020337 TI - The unit of care revisited. PMID- 4020338 TI - The diet-heart dyad and preventive cardiology: why don't we preach what we practice? PMID- 4020339 TI - Characterization in Micromonospora inyoensis of aminoglycoside acetyltransferase activity not previously encountered among actinomycetes. AB - Extracts of Micromonospora inyoensis contain aminoglycoside acetyltransferase activity not previously encountered among actinomycetes. Neomycin and its derivatives (excluding butirosin) are good substrates as is the novel aminoglycoside apramycin, whereas the gentamicins and kanamycins are utilized poorly if at all. Sisomicin, which is produced by M. inyoensis, is not acetylated. When neomycin was modified by extracts of M. inyoensis the product, most probably 3-N-acetylneomycin, was inactive against cell-free protein synthesis. PMID- 4020340 TI - Antigenic population changes of Leptospira biflexa strains grown under the selective pressure of factorial antibodies. AB - Serovars jequitaia and tororo of Leptospira biflexa were cultured in the presence of homologous factor serum containing factorial antibodies (FcAbs) to their major antigens. After 39 serial passages they were then re-tested to determine whether their major antigens had remained unchanged. It was found that each parent strain had been replaced by an antigenic variant. The disappearance of each parent strain and its replacement by an antigenic variant was attributed to the selective conditions imposed by FcAbs. The antigenic variants behaved like true mutants. They lacked the major serovar antigens of the parent strains and had acquired some major antigens similar to those of two different serovars, one of which belonged to the same serogroup as the parent strain and the other to a different serogroup. A comparison of the major antigens of the parent strains with those of their antigenic variants indicated that factorial antibodies may be used selectively to obtain antigenic variants with a predefined pattern of major antigens. PMID- 4020341 TI - The all2 gene is required for the induction of the purine deamination pathway in Schizosaccharomyces pombe. AB - Five mutants were isolated at the all2 gene on the basis of their inability to utilize hypoxanthine as a sole source of nitrogen. These mutants failed to utilize the purines adenine, hypoxanthine, xanthine, uric acid, allantoin and allantoic acid, although they could utilize urea and ammonium. The all2 mutants appeared to be defective in purine induction of uricase, allantoinase, allantoicase and ureidoglycollase activities but retained wild-type activity of the constitutively synthesized urease. The all2 mutations were recessive. PMID- 4020343 TI - Subcellular localization of D-glucanases in Bacteroides oralis Ig4a. AB - Three D-glucan-hydrolysing enzymes from Bacteroides oralis Ig4a have been isolated. Two of them are dextranases which hydrolyse (1----6) but not (1----3) linked alpha-D-glucans; one (EC 3.2.1.11, 1,6-alpha-D-glucan 6-glucanohydrolase) is localized in the periplasm, and the other, which is an exo-enzyme (EC 3.2.1.70, 1,6-alpha-D-glucan glucohydrolase), in the cytoplasm. The third is a mutanase (EC 3.2.1.59, 1,3-(1,3;1,4)-alpha-D-glucan 3-glucanohydrolase) that hydrolyses (1----3) but not (1----6) linked alpha-D-glucans, and is present only in the cytoplasm. PMID- 4020342 TI - Incorporation of fluorotryptophan into triostin antibiotics by Streptomyces triostinicus. AB - The quinoxaline chromophores of the antibiotics produced by Streptomyces triostinicus are derived from tryptophan. Protoplasts of this organism made novel products when they were incubated with DL-5-fluorotryptophan or DL-6 fluorotryptophan. When added to batch cultures of the organism, DL-5 fluorotryptophan, at concentrations as low as 10 microM, inhibited both mycelial growth and triostin production, but gave rise to novel products. These have been characterized, using fast atom bombardment mass spectrometry, as novel triostins in which one or both of the quinoxaline rings contain an atom of fluorine. The chromatographic properties of the triostins arising from the incorporation of DL 5-fluorotryptophan are very similar to those of triostins containing chlorine or bromine at position 6 of the quinoxaline ring; they are clearly different from those having a chlorine atom at position 7. Accordingly, it is suggested that the carbon atom at position 5 of the indole ring of tryptophan ends up at position 6 of the quinoxaline ring system in triostins A and C. PMID- 4020344 TI - Nucleic acid relationships among the anaerobic mycoplasmas. AB - The genetic relatedness between twelve selected strains among four distinct serovars of anaerobic mycoplasmas was studied using [3H]DNA-DNA hybridization, and the results were compared with data obtained from biochemical and serological tests. Radiolabelled DNA probes were prepared from five strains representing four serovars. Based on the homology results, the anaerobic mycoplasmas can be divided into five distinct groups representing five distinct species and two distinct genera. There are two species in the Anaeroplasma bactoclasticum serovar 1 group represented by strains JR and A-2, one species in serovar 2, one species in A. abactoclasticum serovar 3 and one among the unclassified serovar 4 anaerobic mycoplasmas. The probe to nonsterol-requiring strain 161 of serovar 4 showed no homology with any of the established nonsterol-requiring Acholeplasma species DNAs, or with Mycoplasma hominis DNA, or with avian DNA which served as a negative control. There was good correlation between the phenotypic and genotypic properties of the five distinct anaerobic mycoplasma species but the results indicate that phenotypic properties are not always adequate for speciation of the anaerobic mycoplasmas. PMID- 4020345 TI - Induction of spheroplasts in Capnocytophaga ochracea. AB - A gentle technique for preparing spheroplasts of Capnocytophaga ochracea strain 25 is described. Cells in the exponential phase were washed with 1.0 M-NaCl, agitated in 1.0 M-NaCl for 2 h at 30 degrees C and exposed to lysozyme in a Tris/salts buffer, pH 7.0. This procedure resulted in 98% spheroplast formation with complete removal of the peptidoglycan layer as detected by both phase contrast and electron microscopy in combination with chemical analysis. PMID- 4020346 TI - Effect of measles virus antibodies on a measles SSPE virus persistently infected C6 rat glioma cell line. AB - Maintenance of measles (SSPE-Lec) virus persistently infected C6 rat glioma cells in medium containing polyclonal measles antiserum resulted in the loss of detectable expression of all measles virus proteins. Removal of these cells from antiserum, however, led to a re-expression of virus proteins and the production of infectious virus. Cloning of antibody-modulated non-expressing cells in the presence of antiserum showed that re-expression of virus proteins was not due to an incomplete curing process following the addition of antiserum, as a large number of non-expressing cell clones developed the capacity to express measles virus antigen at different periods after removal of antiserum. Irradiation of persistently infected cells to give a non-growing culture showed that modulation was not mediated by a selection and outgrowth of a small percentage of non expressing cells originally present in the culture. Antibody directed against C6 membrane proteins did not lead to modulation and it was also shown that only monoclonal antibodies with neutralizing activity could affect intracellular antigen expression. Immunoglobulin Fab fragments with neutralizing activity also had modulating activity. Although all modulated cell clones were more susceptible to homologous virus infection than control C6 cells, it was not possible to rescue any defective measles virus which may have been maintained in the culture. PMID- 4020347 TI - Sindbis virus glycoproteins are abnormally glycosylated in Chinese hamster ovary cells deprived of glucose. AB - We have previously demonstrated that Sindbis virus infection of Chinese hamster ovary (CHO) cells altered the protein glycosylation machinery of the cell, so that both normal, full-size (nine mannose-containing) oligosaccharides and abnormal, "truncated' (five mannose-containing) oligosaccharides are transferred from lipid-linked precursors to newly synthesized viral membrane glycoproteins. In the present studies, we have examined the precursor oligosaccharides on viral glycoproteins that were pulse-labelled with [3H]mannose in the presence or absence of glucose, since glucose starvation of uninfected CHO cells has been reported to induce synthesis of truncated precursor oligosaccharides. Pulse labelling in the absence of glucose led to a greater than 10-fold increase in the relative amount of the truncated precursor oligosaccharides being transferred to the newly synthesized viral glycoproteins and to an apparent underglycosylation of some precursor viral polypeptides, with some asparaginyl sites not acquiring covalently linked oligosaccharides. The mature virion glycoproteins from CHO cells which were pulse-labelled in the absence of glucose and then 'chased' in the presence of glucose contained proportionately more unusual Man3GlcNAc2-size oligosaccharides. These small neutral-type oligosaccharides were apparently not as good a substrate for further processing into complex acidic-type oligosaccharides as the normal Man5GlcNAc2 intermediate that results from the full-size precursor oligosaccharides. PMID- 4020348 TI - Measurement of interferon from in vitro stimulated lymphocytes by bioassay and monoclonal antibody-based immunoassay. AB - Peripheral blood mononuclear cells (PBMC) derived from healthy individuals were stimulated with u.v.-inactivated Newcastle disease virus and the cell supernatants were assayed for both antiviral activity and alpha interferon (IFN alpha) immunoreactivity. IFN-alpha concentrations determined by two immunoradiometric assays (IRMAs) based on monoclonal antibodies that recognize different IFN-alpha subtypes correlated well together (r = 0.96) and with interferon concentrations determined by the two bioassays (r = 0.82 to 0.89), but the agreement between the results of the two bioassays was not as close (r = 0.79). As judged by the agreement between determinations on duplicate inductions of the same PBMC, the IRMAs were considerably more precise than the bioassays. Despite the use of a common IFN standard there were marked differences in the absolute titres of IFN determined by the IRMAs and bioassays, highlighting the difficulties in standardizing assays for IFN-alpha. The IRMA results suggest that there are no major differences in the spectrum of IFN-alpha subtypes produced by healthy individuals under conditions of viral stimulation. PMID- 4020349 TI - Severity of fever in influenza: studies on the relation between viral surface antigens, pyrexia, level of nasal virus and inflammatory response in the ferret. AB - Previous work has shown that fever in influenza of ferrets occurs following release of endogenous pyrogen from virus-phagocyte interaction in the upper respiratory tract (URT), and suggested that the poor inflammatory response and correspondingly low fever elicited by A/Puerto Rico/8/34 (H1N1), compared with H3N2 reassortant clones of A/Puerto Rico/8/34-A/England/939/69, were related to its H1 and N1 surface antigens. Nasal virus levels, inflammatory and pyrexial responses produced in ferrets by clones 31 (H3N1) and 64b (H1N2) of the same reassortant system suggested a connection between the H1 antigen and low inflammatory response, but results were not conclusive. Unlike A/Puerto Rico/8/34, two recent H1N1 isolates, A/USSR/90/77 and A/Fiji/15899/83, produced a high inflammatory response yet low fever despite large amounts of virus in the URT, suggesting that either no connection exists between the acquisition of the H1 antigen and production of a low inflammatory response, or the H1 antigen of recent isolates, whilst antigenically related to that of A/Puerto Rico/8/34, is biologically different. PMID- 4020350 TI - [Polycystic renal diseases: morphology and genetic counseling]. AB - The designation "polycystic kidneys" is vague and causes considerable confusion. This term comprises a number of affections, characterized by the presence of renal cysts. Cystic kidneys may be hereditary or sporadic. The defect may be isolated or occur as part of a syndrome. The identification of the exact nature of the lesion is therefore of paramount importance, not only for the prognosis of the propositus, but especially for the correct genetic counselling of the family. In this context, the perinatal autopsy represents an irreplaceable method of investigation. Since the pathogenesis of many, if not all, types of polycystic kidneys remains unknown, a practical classification must be based on gross and microscopic pathologic study, clinical features, and family history. Osathanondh and Potter (1964) distinguished four varieties, based on morphological findings, revealed by microdissection. Unfortunately, not all types of cystic kidneys are included in this classification. Moreover, their type III cystic kidney collects a number of clearly different entities. Nevertheless, once one is familiar with its deficiencies, the Osathanondh and Potter classification is still very useful. PMID- 4020351 TI - [Determination of fetal karyotype in the first trimester of pregnancy by direct examination of chorionic villi]. AB - Chorionic biopsy during the first trimester of pregnancy allows fast and precise study of fetal karyotype. Considering the results of our ten prenatal diagnoses, we discuss the advantages and the risks of this method. PMID- 4020352 TI - [Prenatal prevention of drepanocytosis: analysis of cellular DNA in 2 cases]. AB - Direct analysis of fetal DNA using restriction endonucleases constitutes a major area of progress in prenatal diagnosis. This recent technology may permit the precise identification of a mutant allele for some diseases, whereas in others it allows the familial segregation of a pathogenic allele to be followed by its linkage to a DNA sequence polymorphism. This type of analysis, available in a few centers, is currently used, among others, for the prenatal diagnosis of hemoglobinopathies such as sickle cell anemia. After fetal cells have been obtained by choriocentesis or amniocentesis, the extracted DNA is exposed to selected restriction enzymes. In the diagnosis of sickle cell anemia the mutant codon responsible for the substitution of glutamic acid by valine in the beta hemoglobin chain is no longer cut by the enzyme Mst II, due to its variance with the normal codon; this difference in fragment length is detected by DNA electrophoresis, and the particular fragments are identified by molecular hybridization with appropriate radioactive probes. Utilizing these methods the genotype of a homozygous normal fetus can be distinguished from that of a homozygote affected or a heterozygote for the sickle mutation of the beta hemoglobin chain. We have recently applied this prenatal methodology to the pregnancies of two couples from Zaire, in which each member was a proven sickle cell carrier. Fetal material was obtained in both cases by amniocentesis at the 16th week of gestation and followed by cell culture. In the first case, a 46, XX fetus, DNA (10 mcg) revealed a heterozygous sickle cell carrier genotype.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4020353 TI - The sine qua non of quality medical care. PMID- 4020354 TI - The belated Viet Nam phantom. PMID- 4020355 TI - Turn about--it's fair play. PMID- 4020356 TI - Blunt chest trauma in children. PMID- 4020357 TI - Infective endocarditis presenting with a pneumothorax in a patient 32 weeks pregnant. PMID- 4020358 TI - Bronchogenic carcinoma and hypercalcemia. PMID- 4020359 TI - Consultation: tibial pain and alcoholism. PMID- 4020360 TI - Evaluation of male infertility. PMID- 4020362 TI - Preoperative blood ordering for vascular surgery. PMID- 4020361 TI - Percutaneous nephrostolithotomy: Ochsner Medical Institutions' experience. PMID- 4020363 TI - Parental alcoholism in opioid addicts. AB - Using the family history method, the authors examined the relationships of parental alcoholism to alcoholism, depression, and antisocial personality disorder among 638 opioid addicts. It was concluded that, compared to addicts without parental alcoholism; addicts with parental alcoholism were more frequently concurrent alcoholics; addicts with parental alcoholism not only had alcoholism more often, but also depression and antisocial personality disorder; among alcoholic addicts, those with parental alcoholism had more severe problems with alcohol abuse; and addicts with parental alcoholism reported more disruptive childhood events. The independent additive effects of disruptive childhood events and parental alcoholism on the severity of addict disorders including alcoholism were also examined. Although alcoholic addicts had experienced more disruptive childhood events than nonalcoholic addicts, these events did not substantially contribute to increasing the severity of alcohol-related problems. Similar results were obtained for depression and antisocial behaviors in these addicts. The conclusions concerning addicts supported some of those described for "familial alcoholism" among nonaddict alcoholics, but other characteristics of alcoholics with familial alcoholism were not found among addicts. PMID- 4020364 TI - Stressful life events associated with endogenous depression. AB - This study addresses the longstanding clinical impression that episodes of endogenous depression have less relationship to environmental stress than episodes of nonendogenous depression. Stress levels of 100 Research Diagnostic Criteria-assessed psychiatric inpatients are retrospectively assessed for the period immediately before episode onset and for an earlier, baseline period. Although pre-episode stress levels are higher in nonendogenous depressed patients than in endogenous depressed patients or psychiatric controls, this difference is due to a higher baseline level in the nonendogenous group. Compared longitudinally, all three groups show an equivalent increase in stressful events from the baseline to pre-episode period. PMID- 4020365 TI - Modeling effects on suicidal behavior. AB - Knowledge of suicidal behavior, i.e., psychiatric patients indicating that they have an acquaintance or relative who has attempted or committed suicide, has been cited as a risk factor in the assessment of suicide potential. The authors evaluated psychiatric patients hospitalized for a suicide attempt (N = 30), serious suicidal ideation (N = 26), or other non-suicide-related reasons (N = 20) and also a control group of 18 patients admitted for orthopaedic surgery. Information derived from a structured clinical interview revealed that suicide attempters have fewer suicidal models than individuals in the other patient groups, and they are more interpersonally distant from the models they do know. Depression level was not positively related to the recall and reporting of suicidal models. Measures assessing suicide-related beliefs revealed that suicide attempters rated suicide as an effective solution for problems to a greater extent that did patients in the remaining three groups. The implications of these results for social learning models of suicidal behavior are discussed. PMID- 4020366 TI - Unbiased criteria for severity of depression in alcoholic inpatients. AB - The internal consistency of the Beck Depression Inventory (BDI) is assessed in 106 inpatient alcoholics by using a latent trait model. The analysis confirms that the BDI measures a single underlying dimension of depressive severity among alcoholics. Seven symptoms discriminate well for severity of depression. These seven--work inhibition, guilt, self-disgust, irritability, indecision, dissatisfaction, and loss of social interest--may represent criteria for depressive severity that are not confounded by chronic drinking, physical withdrawal, unique personality organization, or life circumstances of alcoholics. Three of the symptoms--dissatisfaction, loss of social interest, indecision--may represent core criteria for depressive severity by virtue of their previously demonstrated ability to discriminate well for severity of depression among both psychiatric and medical inpatients. PMID- 4020367 TI - Age trends of early awakening and feeling worse in the morning than in the evening in apparently normal people. AB - Age-specific prevalences of early awakening and feeling worse in the morning than in the evening were studied in 6034 subjects (schoolchildren, students, and employees) aged 9 to 60 years. Early awakening was found to be significantly more prevalent in males at most ages. In both sexes, early awakening was least prevalent in subjects aged 13 to 26 years and feeling worse in the morning than in the evening was most prevalent in subjects in their 20s. In subjects older than 21 years, the age trend of early awakening was a uniform increase, while that of feeling worse in the morning than in the evening was a uniform decrease. These two symptoms show roughly opposite age trends. Increasing prevalence of early awakening with age in endogenous depressives can be viewed at least partly as a reflection of the normal aging process. PMID- 4020368 TI - Marital status of schizophrenic and alcoholic patients. AB - Previous reports from treated psychiatric populations have reported a higher risk of mental illness among married females; however, community surveys often do not show this prevalence. Three referral groups, consisting of 488 subjects who were mentally ill but not seeking psychiatric treatment, provided a third type of population. For both sexes, combined drug and alcohol abusers were more likely to be divorced than to be married when compared to the rest of the study population (p less than .05). Both schizophrenia and drug and alcohol abuse showed differential findings by marital status and by sex, with the likelihood of more mentally ill females than males being married in these treatment populations. PMID- 4020370 TI - Treatment of anorexia nervosa in a young adult patient with diabetes mellitus. AB - The case history and clinical course of a young adult patient who had diabetes mellitus and developed anorexia nervosa is described. This patient was referred for long-term inpatient treatment after short-term treatment efforts had failed. Inpatient treatment utilizing behavior modification, psychodynamic therapy, and family interventions in a long-term therapeutic milieu is discussed. This case is also contrasted with previous accounts of diabetic adolescents who developed anorexia; however, it is noted that no other reports exist of cases of anorexia developing in adult insulin-dependent diabetic patients. The necessity of integrating a variety of therapeutic techniques in such cases is discussed. PMID- 4020369 TI - Major depression and carbon monoxide-induced parkinsonism: diagnosis, computerized axial tomography, and response to L-dopa. AB - A case of major depressive disorder complicated by carbon monoxide (CO)-induced Parkinson's syndrome is reported. Computerized axial tomography (CAT) revealed bilateral globus pallidus necrosis. Clinical, CAT, and neuropathological findings in other cases of CO encephalopathy with and without parkinsonism are reviewed. The utility of CAT in the diagnostic workup and in following clinical course is discussed, as are the difficulties of making a diagnosis of an antecedent primary psychiatric disorder in the presence of neurological and psychiatric sequelae of CO intoxication. There was no clinical response to a tricyclic antidepressant, but both the mood and movement disorders responded fully to L-dopa. The implications of these findings with regard to the central neurochemical pathophysiology in this patient and in major depressive disorder in general are discussed. PMID- 4020371 TI - Group psychotherapy with multiple personality patients. AB - Group psychotherapy with multiple personality patients is an infrequently utilized technique. In a homogeneous group composed of multiple personality patients, the technique of group psychotherapy is examined in detail. The group setting, selection of patients, and group composition are described. Therapeutic issues involving group process, intrapersonal dynamics, transference, countertransference, co-therapy, and termination are examined. Finally, psychotherapy with the group of multiple personality patients is contrasted with group psychotherapy with borderline patients and incest victims. PMID- 4020372 TI - Sexual criminality and hypnotizability. AB - Thirty-three sexual offenders, 18 of whom had been convicted of rape, nine of pedophilia, and six of incest, were studied. Two thirds of the subjects had histories of "spontaneous self-hypnotic" experiences (dissociations); seven of these were DSM-III multiples and six were probable multiples. This group had very high hypnotizability scores. The other one third without histories of "spontaneous self-hypnosis" had normal scores. It was concluded that spontaneous self-hypnosis contributed to the perpetration of the crimes in many of these cases, although other factors also directed the antisocial behaviors. PMID- 4020373 TI - Goal attainment scaling with hospitalized sexual offenders. AB - Forty-six hospitalized sex offenders participated in a 6-month evaluation of treatment outcome. This study used the concept of goal attainment scaling, an individualized, scaled description of personal goals, for measuring therapeutic outcome. Conjoint therapist and patient goal setting resulted in 180 treatment goals being set. At follow-up, 38 patients exceeded the "expected" success level on a total of 159 treatment goals, whereas eight patients only made minimal progress on 21 of their 40 selected goals. Despite the benign clinical improvement shown by most patients, few patients actually achieved the best anticipated level of attainment on all of their personal goals (usually three to six goals). Retrospective review of all goal attainment scaling protocols indicated that four major content dimensions account for nearly all of the goals devised: sexual deviation, 30 goals; anger and emotional expression, 64 goals; self concept, 31 goals; and poor interpersonal relations, 51 goals. These goal oriented profiles may have important ramifications for the future assessment, program planning, and rehabilitation of convicted sex offenders. PMID- 4020374 TI - Dimensions of posttraumatic stress disorder among Vietnam veterans. AB - DSM-III criteria and clinical models of stress are used to identify discrete dimensions of posttraumatic stress disorder. The authors test the hypothesis that war trauma differentially affects four dimensions of posttraumatic stress- intrusive imagery, hyperarousal, numbing, and cognitive disruption--by studying data from 251 Vietnam veterans probability sampled in seven sites. The hypothesis was confirmed. Different dimensions of stress symptomatology are found to vary across individuals exposed to different types of war trauma. Stress responses to war trauma also differ by race of the veteran. The relationship between stressors and symptomatology change over time, indicating specific experiences are related to particular long-term patterns of posttraumatic stress disorder. PMID- 4020376 TI - Hostility, somatic symptoms, and hypochondriacal fears and beliefs. AB - The authors administered self-rating scales of anger-hostility, somatic symptoms, and hypochondriacal fears and beliefs to seven groups of patients and nonpatients. Somatic symptoms were positively correlated with anger-hostility and were negatively correlated with feelings of friendliness; the correlation coefficients ranged from low to moderately high and were significant in most groups. Somatic symptoms tended to be associated more strongly with symptoms of anxiety and depression than with those of hostility. The associations of hypochondriacal fears and beliefs with hostility were inconsistent, varied between groups and with the concern measured. The findings do not support the view that anger or hostility are main or specific etiological factors either in somatization or in hypochondriacal fears or beliefs. PMID- 4020377 TI - Assessing pathology in the separation-individuation process by an inventory. A preliminary report. AB - There is growing clinical evidence implicating disturbances in the separation individuation phase of child development to adult psychopathology, particularly the borderline personality disorder. The clinical manifestations of such disturbance have been described by several clinicians and theoreticians. The authors have developed an inventory, based on these observations, designed to assess adult manifestations of disturbances in the separation-individuation process. The inventory was given to subjects meeting DSM-III criteria for borderline personality disorders and to a random university employee control group. The subject group had significantly higher scores than the control group. Although more research is needed to further establish the inventory's validity and reliability and to better define its scoring, the preliminary data indicate that it does assess adult manifestations of pathology in this developmental process. PMID- 4020375 TI - Ordination and cognitive complexity as related to clinical depression. AB - Personal construct psychology has contributed substantially to our understanding of psychopathology. The few studies of personal construct psychology in depression have focused on the content of self-constructs and cognitive complexity. The purpose of this study was to examine the construct system in depressed patients by investigating the relation of depressive symptoms to the content of constructs about others, cognitive complexity, and ordination. Participants were divided into three groups of 25. The depressed group had either a major depressive episode or dysthymic disorder; psychiatric controls had nonaffective psychological disorders; normal controls were hospital employees who had not exhibited psychological distress. Results indicated no differences among the three groups in cognitive complexity. However, normal controls exhibited a higher degree of ordination than either patient group. Furthermore, depressed and psychiatric controls utilized ambiguous constructs more than normal subjects. Finally, symptom severity within the depressed group related to the use of ambiguous and undesirable constructs. On the basis of these and others' results, a "two-level" personal construct explanation of depression is offered. On a comprehensive level, ordination and the use of ambiguous constructs could be viewed as relating to general psychological adaptation, whereas negative self construing (and perhaps ambiguous construing) may relate more directly to depression. Therapeutic implications and directions for future research are discussed. PMID- 4020378 TI - Handedness and alcoholism. AB - One hundred thirty-six alcoholic men and 48 alcoholic women admitted consecutively to an adult alcohol and substance abuse unit were studied in an attempt to replicate previous reports of an association between alcoholism and handedness. Each individual received a structured admission interview, and handedness was determined by a modification of the Edinburgh Inventory. Left handedness was more frequent in men with alcoholic fathers and in first-born men. These data are discussed in the context of a recent theory relating left handedness, immune disease, developmental learning disorders, and fetal testosterone. PMID- 4020380 TI - Tryptophan hydroxylase activity in the brains of controls and parkinsonian patients. AB - The activity of tryptophan hydroxylase was measured in nine regions of human brains from controls and patients with Parkinson's disease, striatonigral degeneration, Shy-Drager syndrome and progressive supranuclear palsy by high performance liquid chromatography with fluorescence detection. The regional distribution of the enzyme activity in control brains was similar to that of serotonergic neurons; relatively high activity was found in the raphe nucleus, locus coeruleus and substantia nigra. The activity in the thalamus in Parkinson's disease and that in the locus coeruleus, raphe nucleus and substantia nigra in striato-nigral degeneration were significantly lower than that of controls (p less than 0.05). In most other brain regions in parkinsonian patients the activity was relatively lower than that of controls except the caudate nucleus and nucleus accumbens where the activity was relatively higher than that of controls. Marked decrease in the enzyme activity in various brain regions was observed in striato-nigral degeneration, Shy-Drager syndrome, and progressive supranuclear palsy. These results suggest that the activity of tryptophan hydroxylase in serotonergic neurons is reduced in the brains of parkinsonian patients and of patients with degenerative nervous diseases. PMID- 4020379 TI - Idiosyncratic pharmacokinetics complicating treatment of major depression in an elderly woman. AB - A 64-year-old woman with major depression developed toxic symptoms while on a regimen of 150 to 200 mg/day of desipramine. Her elimination half-life for desipramine was found to be greatly prolonged, at approximately 150 hours. Her ability to metabolize diphenhydramine and lorazepam was found to be impaired as well. Study of the elimination kinetics of desipramine in three of the patient's sisters provided some support for the existence of a genetically determined metabolic defect. Knowledge of those idiosyncratic pharmacokinetics had important implications for diagnosis and treatment in this case. PMID- 4020381 TI - The hypothalamic and neurohypophysial oxytocin content as influenced by desmethylimipramine in normal and pinealectomized white male rats. AB - Pinealectomized, sham-operated and non operated control rats were injected intracerebroventricularly (i.c.v.) with a single dose of desmethylimipramine hydrochloride (DMI; 20 micrograms, dissolved in 10 microliters of normal saline); after 4 hours they were decapitated and the hypothalamic and neurohypophysial oxytocin content was bioassayed using the milk-ejection effect in vitro. DMI decreased oxytocin content of the hypothalamus and neurointermediate lobe in non operated and sham-operated animals. In pinealectomized rats the oxytocin content of the hypothalamus and neurointermediate lobe diminished and could be further reduced by an i.c.v. DMI injection. As shown in animals pretreated with phenoxybenzamine, these events might be only partially related to an increase of alpha-adrenergic transmission. PMID- 4020382 TI - Tolerance to or facilitation of pharmacological effects induced by chronic treatment with the beta-adrenergic stimulant clenbuterol. AB - The effect in mice of chronic administration of the beta-adrenergic agonist clenbuterol was studied using four pharmacological tests, two of which are predictive of antidepressant activity in man. The suppressive effect of acute administration of the beta-adrenergic agonist in two tests unrelated to antidepressant activity, locomotor activity and investigation of food, was attenuated after chronic treatment. However, in the two tests which are predictive of antidepressant activity, antagonism of reserpine induced hypothermia and potentiation of yohimbine toxicity, the effect of clenbuterol was greater following chronic treatment. PMID- 4020384 TI - Whose rights come first? PMID- 4020385 TI - Induction of antitumor immunity employing live tumor cells and maltose tetrapalmitate. AB - Several protocols employing a new immunoadjuvant, maltose tetrapalmitate (MTP), were tried in an effort to obtain immunization against a weakly immunogenic transplantable mammary adenocarcinoma, 13762, in syngeneic Fischer rats. Effectiveness of immunization was measured by rejection of tumor or reduction in tumor growth, by alteration in survival time after tumor challenge, and by proliferation in vitro of spleen cells of animals tumor-sensitized by killed tumor cells and tumor extracts. No success in the induction of tumor rejection was achieved by employing killed tumor cells or 3 M KCl tumor extracts used in either the presence or absence of MTP. Only a low dose of viable tumor cells elicited tumor rejection immunity when combined with MTP treatment given three times weekly. Spleen cell proliferation of tumor-sensitized animals was obtained in the case of live cells and 3 M KCl extract immunization, and was specific for the type of antigen (killed cells or soluble) preparation employed. PMID- 4020383 TI - Subcellular distribution of glutamic acid decarboxylase in rat brain regions following electroconvulsive stimulation. AB - Electroconvulsive stimulation of rats evoked significant increases of glutamic acid decarboxylase (GAD) activity in the synaptosomal fractions of neocortex (including white matter) and hippocampal formation. The elevation of synaptosomal bound GAD activity was not significant in cingulate cortex, striatum, caudal brainstem and thalamus. The electroconvulsive shocks had no effect on the GAD activity of the cytoplasmic fractions of any brain regions investigated. The highest physiological level of synaptosomal GAD activity was found in thalamus, followed (in decreasing order) by striatum, hippocampus, cingulate cortex, caudal brainstem and neocortex. PMID- 4020386 TI - Tissue distribution of breast cancer-associated antigens defined by monoclonal antibodies. AB - Balb/c mice were immunized with membrane preparations of primary and metastatic breast carcinomas or with live breast cancer cell lines. Sixty-two fusions were performed between immune splenocytes and SP2/0 mouse myeloma cells, and 107 hybridomas were cloned that produced antibody reactive with breast cancer membrane extract, cell lines, and frozen sections, but not with normal tissue membrane extracts or a human fibroblast line. Ninety-four monoclonal antibodies were purified and tested for binding to 16 normal tissue frozen sections and five blood cell types. Thirty-five of the 94 antibodies were also tested on breast cancer sections from 21 patients, 14 breast cancer cell lines, and 11 nonbreast tumor sections. Two of 94 antibodies showed no reactivity to any of the 21 normal tissues or 11 nonbreast neoplasms studied. These two antibodies, 451B7 and 452F2, bound 60% of the breast cancer cell lines and 25% of the breast cancer tissue sections. Eight additional antibodies bound three or fewer of 21 normal tissues. These antibodies bound 25-85% of breast cancer sections, 0-75% of breast cancer cell lines, and many of the nonbreast cancers. A comparison of normal tissues and nonbreast tumors bound by the breast cancer-reactive antibodies indicated that most of the cross-reacting normal tissue structures were epithelial in origin, and that the most cross-reactive nonbreast cancers were those of secondary sex organs (uterus, prostate, ovary). PMID- 4020387 TI - Species variability for toxicity of free and liposome-encapsulated muramyl peptides administered intravenously. AB - Muramyl dipeptide and muramyl tripeptide in free form or encapsulated within multilamellar liposomes were injected intravenously into (C57BL/6 X C3H)F1 mice and strain 2 guinea pigs to evaluate their potential acute, subacute, or chronic toxicity. Animals received either single or multiple (X 3, X 4, X 6, X 8) injections. A definite species variation was established with regard to the toxic nature of muramyl peptides. Mice failed to exhibit any changes of a clinical, biochemical, functional, or morphological nature in response to repeated intravenous administrations of high doses of muramyl peptide (free or in liposomes). In contrast, strain 2 guinea pigs were very sensitive to muramyl peptide, regardless of the dose or number of injections, or whether it was given in liposomes or as micelles (free form). Most guinea pigs exhibited vascular pathology reminiscent of the Schwartzman phenomenon. Further toxicity studies of muramyl peptides administered at relevant biological doses are recommended, as well as studies aimed at elucidating the reasons for the species variations. PMID- 4020388 TI - Familial progressive external ophthalmoplegia with multisystem abnormalities: "new" features raising nosological problems. AB - A 32-year-old female presented with progressive external ophthalmoplegia (PEO) and multisystem abnormalities, strikingly associated with myotonia and muscle hypertrophy. These two features were not found in her brother, who had a complex neuromuscular disorder complicating chronic PEO. In both subjects muscle biopsy revealed "ragged-red" fibres and myofibres containing glycogen granules, which were never bound by membranes. A severe demyelinating neuropathy was revealed by electrophysiological and morphological studies. Cranial CT scan showed extensive demyelination of the cerebral white matter. Genetic studies demonstrated that this familial syndrome is transmitted as an autosomal recessive trait. PMID- 4020389 TI - Parkinsonism, basal ganglia calcification and epilepsy as late complications of postoperative hypoparathyroidism. AB - A patient with post-thyroidectomy hypoparathyroidism, basal ganglia calcification, parkinsonism and seizures is reported. The parkinsonism was resistant to levodopa therapy but was not significantly improved by the correction of hypoparathyroidism. Previously reported cases are discussed, as well as the relationship between hypoparathyroidism, calcification of basal ganglia, parkinsonism and epilepsy. PMID- 4020390 TI - Two siblings with multiple intracranial haemangiomatosis with calcification. AB - Two siblings with multiple intracranial haemangiomatosis are reported, each having psychomotor retardation, epilepsy and gyriform type calcification in the occipital and frontal lobes. There were haemangiomas in one autopsy case with calcification in the deep layers of the cortex and subcortical white matter. PMID- 4020391 TI - Rhinocerebral mucormycosis in a diabetic ketoacidotic patient. AB - A 51-year-old, ketoacidotic diabetic with the rare neurological complications of rhinocerebral mucormycosis is reported. The clinical presentation was characterized by initial severe frontal headache, rapid visual loss with complete external ophthalmoplegia and intracranial spread by invasive fungal growth. Its course and fungostatic therapy with amphotericin B and ketoconazole are described and the literature reviewed. PMID- 4020392 TI - Successful treatment of tuberculous brain abscess. AB - A case of tuberculous brain abscess occurred in spite of 4 months' treatment of pulmonary tuberculosis with a triple drug anti-tuberculous regimen. Surgical removal and further chemotherapy were successful. PMID- 4020393 TI - Neuropsychological and EEG evaluation in exposure to trichloroethylene. AB - After 1 year of exposure to trichloroethylene, reversible neuropsychological impairment and persistent EEG paroxysms were observed in one patient. The improvement of neuropsychological performances and the persistence of severe EEG abnormalities after withdrawal of the toxin suggest "functional" cerebral damage after prolonged exposure to trichloroethylene. PMID- 4020394 TI - Early diagnosis and treatment of herpes simplex encephalitis. PMID- 4020395 TI - Somatosensory evoked potentials in patients with thalamic lesions. AB - Somatosensory evoked potentials (SEPs) were recorded in 20 patients with thalamic lesions confirmed by CT (10 with infarction, 10 with haemorrhage). The changes in SEP configuration are discussed in their relationship to clinical symptoms. Four types of SEP abnormality produced by thalamic lesion are distinguished: (1) "FF" type, (2) "N20/P23 dissociation" type, (3) "N18/N20 false shift" type, and (4) "reduced early component" type. It was shown that clinically similar lesions might produce different SEP patterns. PMID- 4020396 TI - Adrenomyeloneuropathy: report of a family and electron microscopical findings in peripheral nerve. AB - A family with adrenomyeloneuropathy (AMN) is reported, whose female carriers showed severe neurological and biochemical abnormalities. Cytoplasmic lamellar inclusions were found in endoneurial cells of the biopsied sural nerve of a male patient. In spite of the peripheral nervous system involvement in patients with AMN, there have been few reports of these inclusions in the peripheral nerves of such cases. PMID- 4020397 TI - Charcot-Marie-Tooth disease: study of a large kinship with an intermediate form. AB - A clinical, genetic, electrophysiological and ultrastructural study of a large kinship with peroneal muscular atrophy is reported. There was a noteworthy homogeneity in the phenotype as well as in the electrophysiological characteristics encountered in 15 affected members aged between 7 and 72 years. The symptoms appeared first in the second decade of life and stabilized by the fourth decade. There was no evidence of linkage of the neuropathy gene to the Duffy blood group locus on chromosome 1. The electrophysiological data in this family as well as the ultrastructural findings confirm that there is heterogeneity in hereditary motor and sensory neuropathy type I, and support the concept of an intermediate form of Charcot-Marie-Tooth disease. PMID- 4020399 TI - Medical centers: source for training future oncologists. PMID- 4020400 TI - Quality of life. PMID- 4020398 TI - Monocular downbeat nystagmus. AB - A patient with sporadic pontocerebellar degeneration and downbeat nystagmus limited to the left eye is described. The nystagmus was not modified by head movements, but was associated with a purely tonic upgaze paresis in the same eye. Absence of internuclear ophthalmoplegia indicated sparing of the medial longitudinal fasciculus. It is suggested that the vertical oculomotor abnormalities are due to dysfunction of the ipsilateral brachium conjunctivum. PMID- 4020401 TI - Radiotherapy's role in local sarcoma control and quality of life. PMID- 4020402 TI - Aggressive chemotherapy for the treatment of breast cancer. PMID- 4020403 TI - Discordant lymphoma versus single-histology lymphomas. PMID- 4020404 TI - Adjuvant therapy in postmenopausal node-positive breast cancer. PMID- 4020405 TI - The place of radiation therapy in the cure of patients with ovarian cancer. PMID- 4020406 TI - Is there a role for adjuvant chemotherapy in cervical cancer? PMID- 4020407 TI - Plasma melatonin and the hormone-dependency of human breast cancer. AB - We studied the 24-hour plasma melatonin profile in three groups of women: normal individuals, women with breast cancer, and women at high risk for breast cancer, to determine the relationship of plasma melatonin to this malignancy. The mean daytime (nadir) and mean nighttime (peak) plasma levels for the normal subjects were 9.1 pg/mL and 70.9 pg/mL, respectively. The mean daytime and nighttime plasma levels, and the range of melatonin day to night differences for women with breast cancer and women at high risk for breast cancer were comparable to each other and to the normal subjects, with no statistically significant differences noted. The patients with breast cancer demonstrated a striking correlation between the melatonin diurnal rhythm and the steroid receptor content of the primary tumor. Women with estrogen (ER) or progesterone (PR) receptor-positive tumors had a significantly lower mean plasma melatonin day to night difference than did patients with ER- or PR-negative tumors. Further, a strong inverse correlation was observed between the plasma melatonin concentration and the quantities of ER and PR in the primary tumor: the lower the plasma melatonin concentration the greater the amount of either receptor in the primary tumor. Plasma melatonin did not correlate with tumor glucocorticoid receptor content or stage of breast cancer among these patients, or with menopausal status, age, parity, or the plasma levels of estrone, estradiol, progesterone, follicle stimulating hormone (FSH), or luteinizing hormone (LH) among all individuals studied. Plasma melatonin was also independent of the degree of risk for breast cancer among the high-risk patients. These findings suggest an important relationship between the plasma melatonin diurnal rhythm and the hormone dependency of human breast cancer, and may have implications for both the prognosis and treatment of this malignancy. PMID- 4020408 TI - Phase II study of recombinant leukocyte A interferon (IFN-rA) plus cimetidine in disseminated malignant melanoma. AB - Thirty-five eligible patients with disseminated malignant melanoma received intramuscular recombinant leukocyte interferon (IFN-rA), 50 X 10(6) U/m2 three times weekly (TIW) for an intended duration of 12 weeks concomitant with daily oral cimetidine, 1,200 mg/d in four divided doses. For all study participants, the median survival time was six months. Among 21 "good risk" patients (performance score [PS] 0, 1 and no prior chemotherapy), we observed seven partial regressions (33%). Six patients had stability of disease (29%), seven had immediate disease progression, and one discontinued treatment after two doses without tumor evaluation due to side effects. Times to disease progression of five patients with regressions of soft-tissue disease were 2.1, 3.3, 3.5, 3.7, and 4.3 months. Two patients had partial regressions of lung nodules for 2.0 and 3.8 months. We observed one regression among 14 "poor risk" patients (PS 2, 3, or prior chemotherapy). A 46-year-old woman with prior treatment had a partial regression of soft-tissue disease for 4.1 months. Four "poor risk" patients achieved disease stability, and nine progressed immediately. Leukopenia (WBC count less than 4,100/microL) affected 21 (66%) of 32 patients with WBC count data. The median count was 3,100/microL; range, 1,300 to 8,400/microL. We detected two cases of mild thrombocytopenia (100,000 and 120,000/microL). Other noteworthy toxicities included moderate-to-severe nausea (34%), anorexia (63%), and fatigue (80%). All patients experienced myalgias. Twenty patients had dosage decreases during the first cycle, and 14 of the 16 patients remaining on study after the first cycle required dosage reductions. The overall response rate is similar to our prior studies with IFN-rA as a single agent using TIW doses of 50 X 10(6) U/m2 and 12 X 10(6) U/m2 among 31 and 30 patients, respectively. PMID- 4020409 TI - Treatment of preleukemic syndromes with continuous intravenous infusion of low dose cytosine arabinoside. AB - Preleukemic syndromes compose a group of acquired bone marrow disorders characterized by dysplastic maturation of hematopoietic cells and peripheral blood cytopenias. These syndromes have been generally considered untreatable. We administered low doses of cytosine arabinoside by continuous infusion for 14 to 21 days (20 mg/m2/d) to 16 patients with preleukemia in various stages of evolution to acute leukemia. Steady state plasma cytosine arabinoside levels ranged from 41.8 to 64.2 nmol/L. Eleven patients demonstrated marked improvement in hematopoiesis and loss of transfusion requirements for periods ranging from two to 27 + months. All but one responding patient developed recurrent pancytopenia, but additional responses to low-dose cytosine arabinoside were achieved in five of five retreated patients. Median overall survival time is 12 months for the 11 responding cases, and nine months for nonresponders. The major toxicity of low-dose cytosine arabinoside is myelosuppression, and most patients required platelet transfusion support and administration of antibiotics. Chromosome analyses demonstrated evolution to a new clone of hematopoietic cells in three patients, and persistence of the same abnormal clone in another patient. These results suggest that low-dose cytosine arabinoside therapy may result in improved hematopoiesis by promoting maturation or by selecting new stem cell clones. Low-dose cytosine arabinoside therapy thus deserves further evaluation both as a single agent and in combination with other agents in the treatment of myelodysplastic syndromes. PMID- 4020410 TI - Phase II study of interferon alpha in metastatic renal-cell carcinoma: a progress report. AB - Partially purified interferon alpha (IFN alpha) was administered to 50 patients with metastatic renal-cell carcinoma (RCC) studied for more than two years. Complete or partial remissions were observed in 26% of the patients. Duration of remissions range from two to 16 months (median, six months). No distinct prognostic factors were clearly identified in the responsive patients, but responses occurred more frequently in men with optimal performance status who had undergone nephrectomy and in whom the metastatic disease was confined to the lungs, pleura, or mediastinum. Leukopenia and granulocytopenia were useful markers of biological activity but did not predict tumor response. Side effects and toxicity at the dosage used (3 X 10(6) units intramuscularly daily) were well tolerated and consisted predominantly of fatigue and asthenia. We concluded that IFN alpha is useful for palliating metastatic RCC, but no impact on survival was demonstrated. Further studies are required to determine the optimal dose, routes of administration, and treatment schedules. PMID- 4020411 TI - Metoclopramide: dose-related toxicity and preliminary antiemetic studies in children receiving cancer chemotherapy. AB - Prior studies in adults have shown that metoclopramide (MCP), when given in high intravenous (IV) doses (2 mg/kg), is a highly effective antiemetic for chemotherapy-induced vomiting. It is well-tolerated in older adults, but younger adults have an increased disposition to acute extrapyramidal reactions (EPRs). Before studying the efficacy of MCP as an antiemetic in children, we first had to establish the safe dose range. We performed a dose-increase MCP toxicity study in children receiving highly emetic chemotherapy such as cisplatin (120 mg/m2) or cyclophosphamide (greater than 900 mg/m2), beginning with a dose of 0.2 mg/kg and increasing the dose in nine steps to 3 mg/kg. MCP was given every two hours for four doses beginning one-half hour before chemotherapy. To reduce the incidence of EPRs, we added concomitant diphenhydramine. In MCP doses less than 2 mg, toxicity was minimal. In doses greater than or equal to 2 mg, 4/27 (15%) had EPRs and 9/27 (33%) had akathisia. Children who received two consecutive days of MCP had a higher frequency of EPRs. Metoclopramide (2 mg/kg) had promising antiemetic efficacy in a preliminary nonrandomized trial. Chemotherapy-experienced children vomited fewer than five times in 9/21 (43%) trials, and new patients vomited fewer than five times in 7/10 (70%) trials. MCP will become more useful as an antiemetic in children if better measures to prevent EPRs can be developed. Chemotherapy-induced emesis has the same negative implications in children as it does in adults and optimum antiemetic regimens can only be discovered by conducting randomized clinical trials in children. PMID- 4020412 TI - Selection bias in clinical trials. AB - Of 90 patients with intermediate or high-grade sarcoma eligible for a randomized trial of adjuvant doxorubicin (Adriamycin, Adria Laboratories, Columbus, Ohio), 48 were not entered: 24 (27%) by physician's choice and 24 refused randomization. Sixty-five percent of lower stage patients were randomized compared with 37% of those with higher stage (P = .02). Patients with extremity lesions were more frequently offered participation in the study (P = .07). Patients with lower stage lesions accepted randomization more readily than those with higher stage lesions (P = .01). As predicted by the higher stage and percentage of central lesions, the disease-free survival of nonrandomized patients was inferior to that of randomized patients (P = .15). Thus, patients at high risk appeared to avoid randomization and adjuvant doxorubicin in this trial, resulting in an inferior disease-free survival for the nonrandomized control group. Important questions generally require randomized trials that reliably determine relative treatment differences. If, however, the patients in a clinical trial are not representative of the entire patient population because of patient and physician selection biases, the generalizability of the results to the entire patient population may be compromised. For example, the prognosis of the general population cannot necessarily be inferred from the selected group in the study. In this study, the randomized and nonrandomized series yielded differing conclusions regarding treatment efficacy, even when an adjustment was made for known prognostic facts. PMID- 4020413 TI - Dichloromethotrexate--a critical reassessment. PMID- 4020414 TI - Combination intraperitoneal chemotherapy. PMID- 4020415 TI - The coordination of arm movements: an experimentally confirmed mathematical model. AB - This paper presents studies of the coordination of voluntary human arm movements. A mathematical model is formulated which is shown to predict both the qualitative features and the quantitative details observed experimentally in planar, multijoint arm movements. Coordination is modeled mathematically by defining an objective function, a measure of performance for any possible movement. The unique trajectory which yields the best performance is determined using dynamic optimization theory. In the work presented here, the objective function is the square of the magnitude of jerk (rate of change of acceleration) of the hand integrated over the entire movement. This is equivalent to assuming that a major goal of motor coordination is the production of the smoothest possible movement of the hand. Experimental observations of human subjects performing voluntary unconstrained movements in a horizontal plane are presented. They confirm the following predictions of the mathematical model: unconstrained point-to-point motions are approximately straight with bell-shaped tangential velocity profiles; curved motions (through an intermediate point or around an obstacle) have portions of low curvature joined by portions of high curvature; at points of high curvature, the tangential velocity is reduced; the durations of the low-curvature portions are approximately equal. The theoretical analysis is based solely on the kinematics of movement independent of the dynamics of the musculoskeletal system and is successful only when formulated in terms of the motion of the hand in extracorporal space. The implications with respect to movement organization are discussed. PMID- 4020416 TI - Quantitative comparison of the structural features of slow and fast neuromuscular junctions in Manduca. AB - The multiterminal slow and fast neuromuscular junctions of the moth Manduca sexta were compared using scanning, thin-section, and freeze-fracture techniques to see what structural features might underlie their functional differences. Slow neuromuscular junctions, here formed on tonic muscle fibers, produce a facilitating e.j.p. the amplitude of which is 1/5 to 1/3 the size of a fast excitatory junction potential (EJP) and the duration of which is nearly four times longer. A slow junction consists of a single terminal branch that is shorter in length than either of the pair of branches that a fast junction forms close together on the muscle fiber. Within the junction, slow nerve terminals exhibit longer, more frequent constrictions and are very varicose compared with fast. Since fast larval junctions on tonic muscle fibers are also varicose (Schaner and Rheuben, 1985), this is unlikely to represent an intrinsic property of the nerve. However, calculations of the length constants of the varicose versus nonvaricose shapes indicate that the effect of passive cable properties on normal functioning may act to limit the length of the slow terminals more than that of fast. Even though the varicose shape can be predicted to prolong the time course of the EJP, calculations show that, at the measured length, this would not explain the very long EJP that is observed. Within the neuromuscular junctions, the synapses are characterized on the muscle membrane by a patch of densely packed particles on the external leaflet and on the nerve membrane by a single linear active zone. The total number of synapses per slow junction is about 1/3 that of fast junctions. There is a weak correlation between average area of the individual postsynaptic particle patches and cross-sectional area of the muscle fibers that transcends nerve and muscle fiber types. The average lengths of active zones from the two types do not differ significantly. However, the number of particles per active zone in slow junctions is about 55% of the number in fast active zones. Chemically fixed slow nerve terminals have a greater density of synaptic vesicles remaining than do fast. If a proportion of the active zone particles represent structures directly involved in the probability of transmitter release, such as Ca++ channels, then the latter two characteristics may jointly reflect differences in capability to release and mobilize transmitter that would partly explain the different EJP amplitude and facilitation properties. PMID- 4020417 TI - Fast and slow nerve growth factor binding sites in human neuroblastoma and rat pheochromocytoma cell lines: relationship of sites to each other and to neurite formation. AB - We studied (a) the distribution and properties of fast and slow 125I-nerve growth factor (125I-NGF) binding sites in cultured human neuroblastoma (NB) cell lines that were categorized as responsive (N+) or unresponsive (N-) to NGF by neurite outgrowth, (b) whether fast or slow sites mediate actions of NGF, and (c) whether NGF-mediated conversion of fast to slow sites occurs in human NB and pheochromocytoma PC 12 cells. In human NB SH-SY5Y cells, the slow sites were trypsin resistant and binding was of high affinity. Loss of binding to the slow sites had a half-time of 25 to 30 min at 37 degrees C and was very slow at 4 degrees C. In contrast, the fast sites were trypsin sensitive and binding was of lower affinity; its dissociation half-time was less than 1 min at 4 degrees C and 37 degrees C. The association rate constants of both sites were about 0.8 to 1.2 X 10(7) M-1 sec-1. Some human NB cells had both fast and slow sites. The N+ human NB lines SH-SY5Y and LA-N-5 had only slow sites. Despite the virtual elimination of fast sites by trypsin in NB MC-IXC cells, remaining slow sites could still efficiently bind 125I-NGF. These observations showed that fast sites are not required for slow site binding, neurite outgrowth, or other demonstrated actions of NGF in some NB cells. In PC 12 cells, 125I-NGF initially bound to fast sites was not directly transferred to slow sites as required for NGF-mediated conversion. The association rate constants of fast and slow sites in PC12 cells were both about 2 X 10(7) M-1 sec-1. The association kinetics were consistent with simple bimolecular reactions in both NB and PC12 cells. The combined evidence in NB and PC12 cells did not support the hypothesis of NGF-mediated conversion of fast to slow sites. PMID- 4020418 TI - Peripheral nerves in shiverer----dystrophic mouse chimeras: evidence that a non Schwann cell component is required for axon ensheathment in vivo. AB - Peripheral nerves in dystrophic mice express multiple axon ensheathment abnormalities. If an intrinsic deficiency expressed within the Schwann cells themselves were to account for this neuropathy, then such cells, existing in a chimera preparation, would be expected to express the same ensheathment abnormalities, whereas a coexisting population of non-dystrophic Schwann cells should not be similarly affected. The genotype of myelinated Schwann cells in shiverer----dystrophic chimera was established with immunocytochemical techniques. Shiverer myelin lacks the P1 component of myelin basic protein (MBP), whereas dystrophic myelin appears to contain normal levels of MBP. No correlation between the ensheathment characteristics of the chimera spinal roots and the genotype of the local Schwann cell population was found; both dystrophic Schwann cell populations expressing normalized ensheathment characteristics and shiverer Schwann cells failing to respond to the local presence of naked axons were observed. These results require that a defective extra Schwann cell component is involved in the pathogenesis of the dystrophic neuropathy. Moreover, the normal realization of that component appears to be a necessary prerequisite for shiverer Schwann cells to achieve full ensheathment competence. Although a definitive identification of the cell type(s) that expresses the dy gene locus has not been achieved in this chimera preparation, the observations are consistent with defective endoneurial fibroblast function. PMID- 4020419 TI - Immunocytochemical mapping of 1B236, a brain-specific neuronal polypeptide deduced from the sequence of a cloned mRNA. AB - The 318-amino acid, carboxy-terminal sequence of the putative brain-specific polypeptide 1B236 was deduced from the nucleotide sequence of its cloned brain specific mRNA. Antisera raised against selected synthetic peptide fragments of this protein were used to map the cellular location of the presumptive gene product in the brains of normal or colchicine-pretreated adult rats. Antisera directed against any of three C-terminally located, but nonoverlapping, nonhomologous, synthetic peptide segments (P5, P6, or P7) produced virtually identical maps of intensely immunoreactive neuropil staining. The immunoreactivity was distributed heterogeneously and was most pronounced within olfactory, somatosensory, and limbic systems, and was more modest in certain motor and auditory structures. In colchicine-pretreated rats, large, multipolar perikarya were observed within the amygdala, caudate-putamen, cingulate, parietal, and piriform cortices, as well as in particular diencephalic and pontine nuclei. Smaller immunoreactive neurons with more limited dendritic extensions were observed in the olfactory bulb, the cerebellar cortex, and the dorsal horn and intermediolateral cell columns of the spinal cord. No immunoreactivity was observed in visceral structures innervated by the autonomic nervous system or in non-neural tissues. In addition to the virtually superimposable maps produced by antisera to all three synthetic fragments selected from the C-terminus of 1B236, some uniquely reactive sites were seen. Antisera to the most N-terminal of the three synthetic immunogens (P5) were reactive with neurons of the medial trapezoid nucleus and in nerve terminals surrounding the deep cerebellar nuclei. Antisera against the most C-terminal synthetic immunogen (P7) were reactive with neurons of the paraventricular and supraoptic hypothalamic nuclei. These data demonstrate that the 1B236 protein is located within selected neuronal elements within functionally related cellular circuits established more formally by other methods. Our data show that protein 1B236-immunoreactive cells share at least the expression of this protein and suggest that these cells may also be related epigenetically or evolutionarily. These data, together with other subcellular, ultrastructural, and electrophysiological properties of 1B236, suggest that this protein could be considered as a prohormone capable of yielding several final candidate transmitter products. PMID- 4020420 TI - Development of neuromuscular specificity in the grasshopper embryo: guidance of motoneuron growth cones by muscle pioneers. AB - In the grasshopper embryo, neuromuscular specificity develops between individual identified motoneurons whose cell bodies are located in the central nervous system, and specific skeletal muscles in the periphery. We previously reported on a class of large mesodermal cells, called muscle pioneers (MPs), that arise early in development (Ho, R. K., E. E. Ball, and C. S. Goodman (1983) Nature 301: 66 69). We suggested that the MPs might be involved in orchestrating the coordinated development of nerve and muscle. In this paper, we describe the development of the MP for coxal muscle 133a in the metathoracic limb bud, and its innervation by two excitatory motoneurons (fast, Df, and slow, Ds). Although many motoneuron growth cones extend out of nerve 5 and quite likely come in contact with the 133a MP between 35% and 45% of development, only Df and Ds display a high affinity for its surface; the other motoneurons innervate more distal leg muscles. When the 133a MP is ablated before arrival of motoneurons in the limb bud, the Df growth cone extends past the location where it normally gets off nerve 5 and continues to extend distally along the same pathway taken by its sibling motoneuron. Although there is a mass of small mesodermal cells in the area where the differentiated coxal muscle 133a normally forms, evidently it does not provide the necessary guidance cue for the Df growth cone. These results indicate the important role played by MPs in the specific guidance of motoneuron growth cones in the grasshopper embryo. PMID- 4020421 TI - Uncrossed and crossed inhibition in the inferior colliculus of the cat: a combined 2-deoxyglucose and electrophysiological study. AB - The cat inferior colliculus (IC) was studied with 2-deoxyglucose (2-DG). By presenting high-frequency tone bursts to one ear and white noise bursts simultaneously to the other, a band of reduced or inhibitory labeling was revealed in the central nucleus (ICC) of the IC ipsilateral to the ear receiving the tone bursts. It was concluded that this ipsilateral inhibition might be related to the organization of excitatory/inhibitory units in ICC. In the opposite ICC, narrow bands of increased labeling were seen. In some animals, the positions of single units were marked, and tone frequencies were presented under 2-DG, which were the same as these units' characteristic frequencies (CFs). The positions of the units coincided with the position of the inhibitory bands, indicating that they were functional isofrequency-inhibitory contours. Unlike higher auditory centers, the binaural inhibitory areas were in register with and not orthogonal to the excitatory isofrequency contours. The inhibitory contours were generally larger than the excitatory contours and became even larger in more caudal sections. Both the inhibitory and excitatory contours extended into dorsal cortex areas of IC. In two other cats, high-frequency tone bursts and white noise bursts were presented to the same ear, and both a band of increased and a band of reduced labelling were found in the IC contralateral to this ear. The inhibitory band was always lateral to the excitatory band and was often smaller. They did not become larger in more caudal sections. The position of a unit in one cat was marked by pontamine sky blue, and the position of the unit coincided with the position of the excitatory band. It was concluded that this lateral inhibitory band represents high-frequency inhibitory sidebands of cells with CFs lower than the stimulating tone. It is concluded that the 2-DG method might reveal hitherto unknown inhibitory systems if stimuli could be combined with diffuse stimuli that raised the general background activity of sensory systems. PMID- 4020422 TI - Structure and expression of the egg-laying hormone gene family in Aplysia. AB - Transcription of the egg-laying hormone (ELH) gene family was examined by characterizing homologous cDNA clones from abdominal ganglion and atrial gland cDNA libraries. All cDNAs contain an exon that spans the coding region (exon III) and one or two additional exons. The tissue-specific expression of the ELH gene family was confirmed by the observation that exon III encodes the ELH precursor protein in the bag cell transcripts and either the A or B precursor proteins in the atrial gland transcripts. The cDNA clones also contain 5' untranslated exons not present in the previously isolated genomic clones. One type of transcript has a 40-base pair segment, designated exon I, contiguous with exon III. A second type of transcript has an additional 149 base pairs of DNA, designated exon II, located between exons I and III. Several genomic clones containing exons I and II were isolated. DNA sequence analysis reveals that exons I and II are directly linked and that they are separated from exon III by an intervening sequence of at least 5 kilobases (kb). Consensus sequences for a putative promotor region and also for RNA splicing and polyadenylation were identified. From this work we can describe a prototype ELH gene complete with identified sequences necessary for the proper initiation of transcription and the subsequent processing of the transcript. PMID- 4020423 TI - Optical mapping of electrical activity in rat somatosensory and visual cortex. AB - We have investigated the use of optical methods for monitoring neuron activity in mammalian cortex. The cortex was stained with a voltage-sensitive dye and fluorescence was simultaneously measured from 124 areas using a photodiode array. Optical signals were detected in rat somatosensory cortex in response to small whisker movements and in visual cortex in response to light flashes to the eye. Relatively large signals were obtained during focal interictal epileptiform discharges induced by bicuculline. The measuring system had a time resolution of milliseconds and a spatial resolution of a few hundred micrometers. Simultaneous, multi-site optical recordings of activity may provide a new and potentially powerful method for studying function and dysfunction in mammalian cortex. PMID- 4020424 TI - Kinetics and autoradiography of high affinity uptake of serotonin by primary astrocyte cultures. AB - Primary astrocyte cultures prepared from the cerebral cortices of neonatal rats showed significant accumulation of serotonin (5-hydroxytryptamine; [3H]-5-HT). At concentrations in the range of 0.01 to 0.7 microM [3H]-5-HT, this uptake was 50 to 85% Na+ dependent and gave a Km of 0.40 +/- 0.11 microM [3H]-5-HT and a Vmax of 6.42 +/- 0.85 (+/- SEM) pmol of [3H]-5-HT/mg of protein/4 min for the Na+ dependent component. In the absence of Na+ the uptake was nonsaturable. Omission of the monoamine oxidase inhibitor pargyline markedly reduced the Na+-dependent component of [3H]-5-HT uptake but had a negligible effect on the Na+-independent component. This suggest significant oxidative deamination of serotonin after it has been taken up by the high affinity system, followed by release of its metabolite. We estimated that this system enabled the cells to concentrate [3H]-5 HT up to 44-fold at an external [3H]-5-HT concentration of 10(-7) M. Inhibition of [3H]-5-HT uptake by a number of clinically effective antidepressants was also consistent with a specific high affinity uptake mechanism for 5-HT, the order of effectiveness of inhibition being chlorimipramine greater than fluoxetine greater than imipramine = amitriptyline greater than desmethylimipramine greater than iprindole greater than mianserin. Uptake of [3H]-5-HT was dependent on the presence of Cl- as well as Na+ in the medium, and the effect of omission of both ions was nonadditive. Varying the concentration of K+ in the media from 1 to 50 mM had a limited effect on [3H]-5-HT uptake.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4020425 TI - The effects of a myasthenic serum on the acetylcholine receptors of C2 myotubes. I. Immunological distinction between the two toxin-binding sites of the receptor. AB - We have examined the effect of a serum from a patient with myasthenia gravis on the binding of alpha-bungarotoxin (alpha-BuTx) to the acetylcholine receptors (AChRs) of a mouse muscle cell line, C2. After a 2-hr incubation, antibodies in the serum reduced toxin binding to C2 myotubes to a maximal extent of approximately 50%. The degradation of surface AChRs could account for the loss of only 5% of sites during the incubation; the remainder, therefore, must have been lost by blockage of binding. To investigate whether the antibodies blocked specifically one of the two toxin-binding sites that each AChR possesses, we used an analysis based on that of Sine, S. W., and P. Taylor, [1981) J. Biol. Chem. 255: 10144-10156). Although the two sites could not be distinguished by their rates of binding of alpha-BuTx, d-tubocurarine (dTC) inhibition of the initial rate of toxin binding revealed that the sites had affinities for dTC that differed by approximately 30-fold. Incubation with the myasthenic antibodies reduced the number of high affinity dTC sites, without affecting those of low affinity. We conclude that the two toxin-binding sites of the AChR are immunologically distinct. PMID- 4020426 TI - Loss of supernumerary axons during neuronal morphogenesis. AB - The morphogenesis of individual neurons was investigated in the cardiac ganglion of the frog. Intracellular injection of horseradish peroxidase shows that mature neurons lack dendrites and have a single axon. Early in development, more than half of the neurons are multipolar and have as many as four processes emanating from their cell body. The most likely mechanism for the developmental transformation of larval neurons is that the supernumerary processes are pruned from the cell body. Supernumerary processes in larval neurons have features characteristic of axons. The processes of larval neurons can be highly branched and extend throughout the target with distinctive varicosities along the length of each process. Electron microscopy shows that all processes of individually injected cells contain clusters of vesicles apposed to active zones. Thus, the larval cardiac ganglion neuron is capable of extending more than one axon from its cell body. PMID- 4020427 TI - Molecular weight determinations of soluble and membrane-bound fractions of choline O-acetyltransferase in rat brain. AB - Three fractions of choline O-acetyltransferase (ChAT) (EC 2.3.1.6) were solubilized from a nerve ending fraction of rat forebrain using three sequential washes of an increasingly chaotrophic nature (100 mM sodium phosphate, pH 7.4; 500 mM NaCl; 2% Triton DN-65) as previously described (Benishin, C.G., and P.T. Carroll (1983) J. Neurochem. 41: 1030-1039). The molecular weights of the soluble (NaP) and membrane-bound fractions (NaCl and 2% Triton DN-65) of ChAT, following partial purification, were determined using either gel filtration on Sephadex G 200, G-100 Superfine, or sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) followed by "Western blotting" and immunochemical visualization of ChAT with four different anti-ChAT monoclonal antibodies (Ab8, Ab9, 4D7, and 1E6). Results obtained with gel filtration indicated that the NaP- and Triton DN-65-solubilized fractions of ChAT had molecular weights in the range of 73,000 to 78,000, whereas the NaCl-solubilized fraction of ChAT had a molecular weight in the range of 230,000 to 240,000. Results obtained with SDS PAGE and Western blotting indicated that all three fractions of ChAT were composed of the same nonidentical subunits. PMID- 4020428 TI - Localized survival of ciliary ganglionic neurons identifies neuronotrophic factor bands on nitrocellulose blots. AB - A novel and sensitive method has been developed to identify ciliary neuronotrophic factors (CNTFs) from tissue extracts after blotting to nitrocellulose paper. The CNTF proteins are required for the in vitro survival of embryonic chick ciliary ganglionic neurons. Tissue extracts containing such CNTFs are electrophoresed using sodium dodecyl sulfate-polyacrylamide gel electrophoresis and transferred to nitrocellulose paper. Purified ciliary ganglionic neurons are seeded on the surface of the nitrocellulose blot, and the culture is incubated for 24 hr in medium lacking CNTF. CNTF can be localized on the blot because it retains its ability to support the survival of the neurons cultured on the nitrocellulose. A band of viable neurons, easily visualized by staining with a vital dye, is supported by the blotted CNTF polypeptide. The number of neurons surviving on the blotted CNTF is related to the amount of CNTF originally loaded on the electrophoretic gel. As little as 2 ng (16 trophic units) of CNTF protein contained in crude tissue extracts can be loaded on the sodium dodecyl sulfate gel and still be recognized by the cultured neurons. This method was used to identify CNTF polypeptides from extracts of adult rat nerve (24,000 and 19,000 daltons) and from tissue found near experimentally induced adult rat brain lesions (24,000 daltons). The electrophoretic mobilities of these peptides are distinct from the previously purified chick eye CNTF polypeptide (20,400 daltons). PMID- 4020429 TI - Localization of choline acetyltransferase within identified motoneurons of the nematode Ascaris. AB - Choline acetyltransferase (CAT) activity has been measured in the nematode Ascaris lumbricoides. Strips of hypodermal tissue which contained branches of single identified motoneurons (Stretton, A.O.W., R.M. Fishpool, E. Southgate, J.E. Donmoyer, J.P. Walrond, and I.S. Kass (1978) Proc. Natl. Acad. Sci. U.S.A. 75: 3493-3497) as well as control strips containing no neural tissue were assayed. In strips of hypodermis which contained branches of excitatory motoneurons (classes DE1, DE2, and DE3), CAT activity was elevated 5 to 10 times compared to control levels. Branches of inhibitory motoneurons (classes D1 and V1) did not add to the level of CAT observed in the controls. These data provide additional support for the suggestion (e.g., del Castillo, J., W.C. deMello, and T. Morales (1963) Experientia 20: 141) that acetylcholine is an excitatory neurotransmitter at nematode neuromuscular junctions. The function of the low level of CAT observed throughout the hypodermis is unknown. PMID- 4020430 TI - Dendritic transport. II. Somatofugal movement of neuronal lysosomes induced by colchicine: evidence for a novel transport system in dendrites. AB - The effect of colchicine injections on the ultrastructural localization of dipeptidyl peptidase II (Dpp II) was studied in the mitral cells of the rat olfactory bulb. In control animals, electron-dense reaction product representing Dpp II activity was observed in lysosomes, lipofuscin granules, short cisternae located close to the granular endoplasmic reticulum, and dense granules. Lysosomes and lipofuscin granules were the most intensely stained organelles. Dpp II-containing organelles were localized mainly to the cell body and were randomly distributed in the perikaryal cytoplasm. Twenty-four hours after a 100-micrograms intracerebroventricular colchicine injection, the distribution of Dpp II containing organelles was drastically altered. Short cisternae and dense granules containing Dpp II reaction product were noticeably absent in these preparations. Lysosomes and lipofuscin granules were depleted from the perikaryal cytoplasm and were concentrated in dendrites. Lysosomes were observed to extend for considerable distances in dendrites where they acquired elongated and dumbbell shapes. The shapes of some of these labeled lysosomes gave the impression that they were actively being "pulled" into the dendrites. These results indicate that microtubules sequester lysosomes to the perikaryal cytoplasm and suggest the presence of a novel transport system responsible for the movement of lysosomes from the cell body to the dendrites. PMID- 4020431 TI - Differential synapse formation and neurite outgrowth at two branches of the metacerebral cell of Aplysia in dissociated cell culture. AB - The metacerebral cell (MCC) of Aplysia californica was isolated with its bifurcate axon from the cerebral ganglion and maintained in vitro under three conditions: (a) with no targets, (b) with identified buccal ganglion neurons B1 or B2 placed near the stump of the large diameter cerebral-buccal connective (CBC) branch, and (c) with B1 or B2 placed near the stump of the small diameter posterior lip nerve (PLN) branch. After 5 days in culture, the two branches differed significantly in the formation of chemical connections and in the extent of neurite outgrowth. Chemical connections characteristic of MCC-B1(B2) connections in vivo were observed in more than 90% of the cultures in which the buccal neuron was contacted by neurites emerging from the CBC branch, but in only 20% of the cultures in which the buccal neuron was contacted by neurites extending from the PLN branch. Neurite outgrowth from the CBC stump was always greater than growth from the PLN and was not affected significantly by the presence of a buccal neuron target at either branch. In contrast, neurite outgrowth from the PLN decreased significantly when the target was contacted by neurites from the CBC branch. These results suggest that two branches of a single neuron can differ in their capacities to form chemical connections. In addition, the two branches show differential growth as a result of target interaction at one of the branches. This simple in vitro system may therefore be useful in exploring the ways in which individual neurons control neurite extension from different branches as they seek to form chemical connections with their targets. PMID- 4020432 TI - Environmental influences in the development of neural crest derivatives: glucocorticoids, growth factors, and chromaffin cell plasticity. AB - The neural crest gives rise to three major adrenergic cell types: sympathetic principal neurons, adrenal chromaffin cells, and small intensely fluorescent (SIF) cells. All of these derivatives synthesize and store catecholamines, but they differ in numerous other characteristics. SIF cells appear intermediate in phenotype between the other two. We have examined the role of several environmental factors in the differentiation of sympathetic principal neurons and adrenal chromaffin cells. In previous studies of young rat adrenal chromaffin cells in dissociated cell culture, differentiated characteristics such as the presence of the enzyme phenylethanolamine N-methyltransferase (PNMT), epinephrine (E) synthesis, and large catecholamine storage vesicles were not well maintained. Here we describe long-term culture of chromaffin cells which, in the presence of micromolar glucocorticoid, maintained all of these characteristics. In addition, chromaffin cells of a variety of ages were found to be dependent on glucocorticoid for long-term survival in culture. In the absence of glucocorticoid, many adrenal chromaffin cells from neonatal rats could be rescued by nerve growth factor (NGF) administration. They extended neurites, as previously described by Unsicker and colleagues (Unsicker, K., B. Krisch, U. Otten, and H. Thoenen (1978) Proc. Natl. Acad. Sci. U.S.A. 75: 3498-3502). In contrast to previous studies, however, with long-term exposure to NGF these cells became indistinguishable from mature sympathetic neurons, as judged by the following morphological and biochemical criteria: increased cell size and loss of intense CA fluorescence in their cell bodies; acquisition of characteristic neuronal ultrastructure, including morphologically specialized synapses; loss of chromaffin granules, PNMT, and E synthesis; and acquisition of neuron markers, including tetanus toxin labeling and immunoreactivity to neurofilament protein. This conversion to neurons was markedly enhanced by addition of a non-neuronal cell conditioned medium (CM) containing a neurite-promoting factor, which acted by increasing the NGF responsiveness of the chromaffin cells. Even chromaffin cells from adult rats, which are known to grow few processes in response to NGF alone, became neuronal in the presence of this CM plus NGF. While converting to neurons, adrenal chromaffin cells transiently assumed an intermediate phenotype resembling type I SIF cells, which suggests particular developmental relationships between the different cell types of the sympathoadrenal lineage.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 4020433 TI - Small intensely fluorescent cells in culture: role of glucocorticoids and growth factors in their development and interconversions with other neural crest derivatives. AB - The neural crest gives rise to a number of adrenergic derivatives, including sympathetic neurons and adrenal chromaffin cells, which contain catecholamines (CAs) but differ in other morphological and functional characteristics. Small intensely fluorescent (SIF) cells, which exist primarily as a minority cell population in autonomic ganglia, are a third cell type in the sympathoadrenal branch of the neural crest lineage. In some respects these cells appear intermediate in phenotype between sympathetic neurons and adrenal chromaffin cells. We established pure dissociated cell cultures of SIF cells from rat superior cervical ganglia (SCG) and used these to study the role of environmental factors in SIF cell development and the relationship of these cells to the other cell types of the sympathoadrenal lineage. When cells from neonatal rat SCG were grown for 3 weeks in the presence of glucocorticoid and in the absence of nerve growth factor (NGF), pure cultures of SIF cells developed. The properties of the cells included (i) small cell size and the occasional presence of short neurites, (ii) intense CA histofluorescence and immunoreactivity for CA synthetic enzymes, (iii) synthesis and storage of CA from radioactive precursors, and (iv) characteristic ultrastructure. The concentration of the glucocorticoid and the presence or absence of non-neuronal cell factors influenced which types of SIF cells developed. In micromolar glucocorticoid most of the cells resembled adrenal chromaffin or type II SIF cells: they displayed immunohistochemically detectable phenylethanolamine-N-methyltransferase (PNMT), synthesized and stored epinephrine, and contained large granular vesicles (100 to 300 nm). When SCG cells were grown in 10(-8) M hormone, many fewer SIF cells developed and a higher percentage of these lacked PNMT immunoreactivity, had neurites, and contained vesicles of smaller mean diameter (70 to 130 nm), similar to those of type I SIF cells in vivo. In the presence of conditioned medium (medium conditioned by non neuronal cells) as well as glucocorticoid, virtually all of the cells morphologically resembled type I SIF cells. In the absence of glucocorticoid, no SIF cells were ever observed after 3 weeks in culture. By following the development of CA histofluorescence and SIF cell ultrastructure in the cultures over time, we demonstrated that SIF cells were not present in large numbers in these cultures immediately after plating, but were induced from an apparently undifferentiated precursor by the hormonal environment, whereas most of the principal neurons died.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 4020434 TI - Glucocorticoid receptors and regulation of phenylethanolamine-N-methyltransferase activity in cultured chromaffin cells. AB - Glucocorticoids are known to regulate the enzyme phenylethanolamine-N methyltransferase (PNMT) in the adrenal medulla of the rat and are thereby thought to control the synthesis of epinephrine. We have examined the details of this relationship in a simplified system, chromaffin cell primary cultures derived from bovine adrenal medulla. Cultured chromaffin cells were found to have a cytosolic, high affinity, saturable glucocorticoid-binding protein with the steroid specificity of a classical glucocorticoid receptor and a Kd of approximately 1 nM. Treatment of cultured cells with dexamethasone or hydrocortisone at any time up to 21 days in culture increased PNMT activity in the soluble fraction of the cell. The concentration of hormone required to produce a half-maximal response was 10 nM dexamethasone when cells were cultured in the presence of 5% fetal calf serum, or 1 nM in a defined serum-free medium. These dose-response relationships are consistent with mediation of this effect by the glucocorticoid receptor. Unexpectedly, however, the glucocorticoid-induced increment in PNMT activity was not inhibited by cycloheximide at concentrations up to 50 microM, and an acceleration of protein synthesis by insulin treatment did not augment the glucocorticoid effect on PNMT. Treatment of the cells with dexamethasone (100 microM) prevented the decline in the epinephrine-to norepinephrine ratio seen over time in culture, an effect consistent with increased PNMT activity. However, there was no effect of dexamethasone on the ability of the cells to secrete catecholamines in response to stimulation with high KCl or 30 microM nicotine.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4020435 TI - Gating properties of acetylcholine receptors at developing rat endplates. AB - The gating properties of acetylcholine receptors (AChRs) change during the development of rat soleus endplates. During the first 3 weeks after birth, the apparent mean channel open time (tau) decreases severalfold and the single channel conductance (gamma) increases 50%. To better understand this phenomenon, we used a combination of noise analysis, analysis of miniature endplate currents (MEPCs), and single-channel recordings to quantify the relative levels of fast and slow AChR activity at developing soleus endplates. When the same endplates were studied with both noise analysis and MEPC analysis, results obtained with the two techniques were strongly correlated, but MEPC analysis yielded higher estimates of the relative amount of slow channel activity. Experiments designed to examine the distribution of fast and slow channels gave no evidence for a gradient of either channel type within individual endplates; rather, fast and slow channels appeared to be mixed together. However, the relative amount of fast and slow channel activity did vary markedly among different endplates within individual muscles. In agreement with earlier studies, we found a progressive decrease in the relative amount of slow channel activity during the first 3 weeks after birth. However, our data indicate that this process begins sooner than reported previously and takes longer to complete. Some of the same endplates that were studied physiologically were also examined in the electron microscope to test the hypothesis that changes in AChR gating might be related to ultrastructural changes such as the formation of folds. The physiological and ultrastructural results were essentially uncorrelated. PMID- 4020436 TI - The morphology of physiologically identified GABAergic neurons in the somatic sensory part of the thalamic reticular nucleus in the cat. AB - Neurons with somatic sensory receptive fields were examined electrophysiologically in the thalamic reticular nucleus of the cat. All cells had receptive fields much larger than those of neurons in the ventral posterior nucleus and were driven by less readily defined somesthetic stimuli. Response latencies to peripheral or medial lemniscal stimulation were, on average, longer than in the ventral posterior nucleus and suggested activation of the reticular nucleus cells by collaterals of thalamocortical relay cell axons arising in the ventral posterior nucleus. When injected intracellularly with horseradish peroxidase, reticular nucleus cells displayed thin axons with intrareticular collaterals and diffuse branches through much of the ventral posterior and posterior thalamic nuclei. Dendrites ended in processes resembling synaptic terminals. Electron microscopic immunocytochemistry of the same part of the reticular nucleus revealed processes immunoreactive for glutamic acid decarboxylase and identifiable as both collateral axon terminals and presynaptic dendrites of GABAergic reticular nucleus cells. These synaptically linked reticular nucleus cells and, in addition, immunoreactive somata and presynaptic dendrites received synapses from at least three varieties of nonimmunoreactive profiles. PMID- 4020437 TI - Structure and function of electrosensory neurons in the torus semicircularis of Eigenmannia: morphological correlates of phase and amplitude sensitivity. AB - Structure-function relations in the electrosensory system of Eigenmannia were examined by labeling physiologically characterized neurons of the dorsal torus semicircularis. The sensitivity of cells to modulations in amplitude (AMs) and modulations in differential phase was determined. Approximately half of the 48 cell types defined by Golgi studies (Carr, C.E., and L. Maler (1985) J. Comp. Neurol. 235: 207-240) were identified in this manner. The majority of the neurons located in laminae (8a, b, c, and d, and 9 exhibited sensitivity to differential phase. In laminae 5 and 7, however, in addition to neurons which were sensitive to differential phase, many cells were found that were purely AM sensitive. Differential phase sensitivity originates in the small cells of lamina 6 (Heiligenberg, W., and G. Rose (1985) J. Neurosci. 5: 515-531), the exclusive termination site of phase-coding afferents from the electrosensory lateral line lobe. Cells that had dendritic extensions into the neuropil of lamina 6 exhibited sensitivity to differential phase, whereas neurons lacking dendrites in this lamina were only excited by AMs. These findings support the notion of a relationship between the morphology and laminar position of a neuron and its function. PMID- 4020438 TI - Independent steroid control of the fates of motoneurons and their muscles during insect metamorphosis. AB - The metamorphosis of insects is controlled by the blood titers of a small number of developmental hormones including a class of steroids, the ecdysteroids. We have studied the developmental fates of several muscles and their motoneurons during the larval-pupal transformation of the tobacco hornworm, Manduca sexta. The endocrine events which trigger pupal development are first, a fall in the blood titer of juvenile hormone, followed by two subsequent elevations of blood ecdysteroids. The small "commitment pulse" of ecdysteroids commits tissues to pupal development, whereas the sustained "prepupal peak" causes the new pupa to be formed (Riddiford, L. M. (1980) In Progress in Ecdysone Research, J.A. Hoffmann, ed., pp. 409-430, Elsevier/North-Holland Biomedical Press, Amsterdam). In the present experiments we were able to correlate specific aspects of the changing blood steroid titers with the degeneration of larval muscles, and with the dendritic regression and death of their motoneurons. The abdominal prolegs, which are the principal locomotory appendages of the caterpillar, are lost during the larval-pupal transformation. We have followed the fates of a proleg retractor muscle, PPRM, and its single motoneuron, PPR. Two other differently fated abdominal muscles not associated with the proleg were also studied. Surgical and endocrinological manipulations showed that PPRM degenerates in response to the rising phase of the prepupal ecdysteroid peak and that interactions with its motoneuron are not involved in the muscle's death. Motoneuron PPR responds to the rising prepupal peak by first reducing its dendritic arbor by 40% and then dying. Other proleg motoneurons regress but do not die, indicating that dendritic regression is programmed separately from neuronal death. Neither the dendritic reduction nor the death of PPR involves interactions with its target muscle. These results indicate that ecdysteroids have independent and parallel effects in the periphery, where they cause muscle degeneration, and in the central nervous system, where they cause dendritic regression and death of motoneurons. PMID- 4020439 TI - Management of acoustic neuromas, 1978-1983. AB - The surgical aspects of 162 consecutive procedures for removal of acoustic neuromas, performed from 1978 through 1983, are reviewed. Nearly all of the procedures were done through a retrosigmoid suboccipital craniectomy. Most used the combined skills of a neurosurgeon and an otological surgeon. Total tumor removal was accomplished in 98% of cases. There have been two recurrences and one postoperative death. The facial nerve was preserved in 81% of procedures. Facial function returned in nearly all of these patients, but the degree of return was variable. The cochlear nerve was preserved in 55 patients, but hearing was present in only 14. The most common complication was cerebrospinal fluid otorhinorrhea (12%); about half of these patients required a secondary procedure. Other complications were meningitis (5%), aspiration (3%), and hemorrhage (2%). During the period reviewed, several changes occurred in management of this disorder. These procedures are now being done by a surgical team. The neurosurgeon performs the intracranial work and the otological surgeon accomplishes the temporal bone dissection. Most patients undergo the operation in the supine rather than the sitting position. During the operation, the facial nerve is monitored continuously by electromyography with intermittent bipolar stimulation. There appears to be continuing improvement in the management of these patients. PMID- 4020440 TI - Stenotic and occlusive disease of the venous drainage system of deep brain AVM's. AB - Angiograms obtained prior to treatment in 53 cases of deep-seated cerebral arteriovenous malformations (AVM's) were retrospectively analyzed with particular attention to the topography of the AVM nidus and the venous drainage. The location of the lesion was determined by a combination of angiography and computerized tomography. Twenty-seven AVM's involved the basal ganglia and thalamus, 12 were located in the corpus callosum, six were intraventricular, and eight involved the mesencephalon and brain stem. Forty-one patients (77.3%) presented with intracranial hemorrhage. Vessel wall irregularities and/or stenosis of the system of the vein of Galen were observed in 14 cases, and occlusion of the deep venous system was present in seven cases. These AVM's showed numerous collateral venous pathways through enlarged medullary and cortical regional veins. There was dominant participation of the basal vein of Rosenthal in all cases. Unique local hemodynamic factors produced by the convergence of the draining veins of the AVM's into the vein of Galen and straight sinus may lead to a higher incidence of stenosis and/or occlusion of the venous drainage. The relatively high incidence of intracranial hemorrhage in these deep-seated AVM's may suggest a relationship between an increased incidence of intracranial bleeding and impaired venous outlets. PMID- 4020441 TI - Successful management of an intracranial arteriovenous malformation by conventional irradiation. AB - The reduction of an intracranial arteriovenous malformation (AVM) by conventional radiation therapy is described in a patient who refused surgery. The 2-year follow-up angiogram documented nearly complete obliteration of the nidus of the AVM, accompanied by progressive narrowing of the arteries supplying the lesion. The scanty literature dealing with this form of treatment is summarized. PMID- 4020442 TI - Post-decompression optic neuropathy. AB - Blindness resulting from a decompressive craniotomy is uncommon. Five patients with intracranial tumors and papilledema who developed a bilateral optic neuropathy during an apparently uncomplicated craniotomy are presented. Symptoms of visual field loss were minimal preoperatively in four. Visual recovery in general was poor. The nerve fiber bundle pattern of visual field loss in these cases implicates the optic disc as the site of damage in this disorder. It is postulated that hypoperfusion to the prelaminar portion of the optic nerve is the underlying cause. PMID- 4020443 TI - Acute cerebral revascularization. AB - Fifteen patients evaluated for acute cerebral ischemia underwent acute cerebral revascularization between March, 1979, and May, 1983. Clinical presentation included crescendo transient ischemic attacks (TIA's) in eight cases, progressing neurological dysfunction in three cases, and completed nonfluctuating deficits in four cases. Nine patients received intravenous heparin but did not improve neurologically. The patients with crescendo TIA's were operated on within 4 hours of their last event; those with progressing deficits were operated on while the deficit was developing, and those with established deficits were operated on 4, 6, 9, and 12 hours, respectively, after the event began. The clinical picture for 10 patients had resolved within 10 hours after surgery. One patient with crescendo TIA's, two with progressing deficits, and two with established deficits had postoperative residual deficits, of which three were mild and two severe. One patient, who had a saphenous vein graft to the middle cerebral artery, developed an intracerebral hematoma. In this prospective noncontrolled nonrandomized study, acute cerebral revascularization was performed safely, had limited risks, and offered the potential to help some patients. Further controlled randomized studies are indicated. PMID- 4020445 TI - The lateral spinal artery of the upper cervical spinal cord. Anatomy, normal variations, and angiographic aspects. AB - The lateral spinal artery corresponds to the most rostral extent of the posterolateral arterial axis of the spinal cord. It supplies the posterior and lateral aspects of the spinal cord, and courses anterior to the posterior roots of the upper cervical spinal nerves (C-1 to C-4), and posterior to the dentate ligament. The lateral spinal artery anastomoses rostrally with the branches of the posterior inferior cerebellar artery (PICA) at the restiform body and laterally with the extraspinal arteries at the emergence of each nerve. It may originate either from the vertebral artery or from the PICA lateral to the medulla. Certain variations will cause an unusual but normal enlargement of the vessel in a specific portion of its course; these variations include vertebral artery duplication, a C-1 or C-2 vertebral origin of the PICA, a C-1 or C-2 occipital origin of the PICA, and an intradural course of the vertebral artery at C-2. Knowledge of these variations in the arterial supply to the area allows for an understanding of the different anatomic peculiarities present and their angiographic importance. PMID- 4020444 TI - Infratentorial arachnoid cysts. AB - The infratentorial compartment represents the second most common location of arachnoid malformations. Ten arachnoid cysts of the posterior fossa, operated on between 1970 and 1983, are reviewed. These lesions, although congenital and developmental in nature, may present at any age, and males are more frequently affected. A high rate of birth-related trauma (50% in this series) is conceivably due to fetal macrocranium, and the enlarged head and psychomotor retardation prevail in infancy and childhood. In arachnoid cysts occurring during adulthood, symptoms and signs more clearly indicate a dysfunction of the posterior fossa. Besides computerized tomography, pneumoencephalography and metrizamide techniques are recommended to rule out a Dandy-Walker syndrome in doubtful cases, and to obtain information about the cerebrospinal fluid (CSF) circulation. It is particularly important to establish the presence and type of communication of cysts with the CSF pathways. Although infratentorial cysts often communicate, they can be space-occupying masses because of increasing CSF retention, which may be due to a ball-valve mechanism or to inadequate communication. The frequently associated hydrocephalus (seven of the 10 cases in this series had hydrocephalus) seemed to be dependent mainly upon mechanical factors. The authors discuss the indications for intracranial surgery versus shunting procedures and report the results achieved by direct cyst excision. PMID- 4020446 TI - Intracranial pressure monitoring by flaccid-cuff catheter in an animal model. AB - Several methods of monitoring intracranial pressure (ICP) are in current use, each with its own advantages and disadvantages. The intraventricular line has been most useful because of the ability to withdraw cerebrospinal fluid to assist in control of elevated ICP. However, masses within the brain or generalized increased ICP may compress the lateral ventricle, making insertion of the catheter difficult or impossible. The intracerebral wick records hydrostatic changes too slowly to be used clinically. Swollen cerebral tissue may occlude the subarachnoid bolt thereby dampening the recorded pressure, and epidural monitors may give falsely high recordings because of irregularities of dura or bone. The authors have developed a flaccid-cuff catheter which has proven in animals to be an effective ICP monitor. There are several advantages, such as easy insertion into the centrum semiovale, rapid response to acute pressure changes, and continued sensitivity for periods of up to 3 weeks. The flaccid catheter cuff has no tension so that the pressure across the membrane is equal to zero, simplifying calibration. This type of cuff is necessary for maximum sensitivity to interstitial, brain-tissue, and gross ICP changes. The flaccid-cuff catheter may prove to be useful in a variety of situations such as after closed head trauma or intracranial surgery to assess elevated ICP caused by edema or evolving hematoma. PMID- 4020447 TI - Perforating branches of the middle cerebral artery. Microsurgical anatomy of their extracerebral segments. AB - Perforating branches of the middle cerebral artery (MCA) were examined under magnification in 50 formalin-fixed brain hemispheres. Perforating vessels varied in number from three to 18, with an average of nine. The greater the number of vessels, the smaller was their diameter. In this study, the perforating arteries were divided into medial, middle, and lateral groupings. Those in the medial group usually arose directly from the MCA main trunk close to the carotid bifurcation. There were usually three vessels in the middle group, which originated not only from the MCA trunk, but also from the MCA collateral (cortical) branches. Common stems, when present, gave rise to individual perforating vessels and occasionally to thin olfactory and insular rami. Perforating arteries in the lateral group varied from one to nine in number. In addition to an origin from the MCA trunk, they also arose from cortical branches supplying the frontal and temporal lobes. The fact that lateral perforating vessels often originated from division sites and from terminal branches of the MCA is of clinical significance, because aneurysms are more commonly located at the MCA bifurcation. Anastomoses were not found among the perforating arteries. In two specimens, a fusion between a perforating artery and the MCA trunk was noted. Since the perforating vessels are obviously end arteries, injury to them must be avoided during operations for MCA aneurysms. PMID- 4020448 TI - Recirculation model following MCA occlusion in rats. Cerebral blood flow, cerebrovascular permeability, and brain edema. AB - A new model for establishing a successful and consistent arterial recirculation has been devised following middle cerebral artery (MCA) occlusion in the rat. A snare ligature was introduced at the stem of the MCA just distal to the lenticulostriate branches, and occlusion and recirculation were performed by pulling and releasing the thread. This method had an advantage over the use of a small clip which caused damage to the artery without good recirculation. Study of local cerebral blood flow using carbon-14 (14C)-iodoantipyrine, of cerebrovascular permeability using 14C-aminoisobutyric acid, and of brain-water content using the microgravimetric technique was performed upon recirculation following various periods of occlusion and compared with the results in permanent ischemia. A reactive hyperemia was noted within the previously ischemic area immediately upon recirculation following either a 30-minute or a 2-hour ischemic period. One or 2 hours later, delayed hypoperfusion developed in this region, but the circulation over the periphery of the ischemic area recovered well. Cerebrovascular permeability was not, however, altered during the time courses studied. Topographic changes in tissue specific gravity were compared between permanent and transient ischemia in the corresponding time-courses. Although there was a greater decrease in tissue specific gravity following recirculation when the ischemic period was maintained longer, edema formation was resolved by recirculation. Further study is required to determine thresholds of ischemic brain damage and edema formation at recirculation following focal cerebral ischemia. PMID- 4020449 TI - Cervical facetectomy and its effect on spine strength. AB - Fourteen cervical spine motion segments consisting of two adjacent vertebral bodies and their connecting ligaments were tested in shear. Five had intact facet joints, five had bilateral facetectomy of 50% or less, and four had bilateral 70% facetectomy. Three to 5 mm of root could be exposed in the specimens with 50% facetectomy, and 8 to 10 mm in those with 70% facetectomy. Anterior-posterior shear tests were run alternately in compression and distraction. Facetectomy was found to have no effect on compression and distraction stiffness. Failure in the 70% facetectomized specimens was due to fracture of the remaining joint at 159 lbs. In the specimens with 50% facetectomy, a fracture load could not be established since failure of the specimen mounting occurred at 208 lbs, as it did in two of the specimens without facetectomy that were tested to failure. The difference in bone fracture at 159 lbs and mounting failure at 208 lbs is significant at p less than 0.05. Bilateral resection of more than 50% of the facet joint significantly compromises the shear strength of a cervical spine motion segment. PMID- 4020450 TI - Diffuse form of primary leptomeningeal gliomatosis. Case report. AB - Primary leptomeningeal gliomatosis is rare, and the diffuse form is even rarer with only three cases reported in the literature. A fourth case is described in this report. Computerized tomography (CT) findings showed hydrocephalus with enhancement of the cerebral cisterns, and analysis of cerebrospinal fluid obtained by lumbar puncture showed many atypical cells. Based on these findings, a diagnosis of leptomeningeal tumor was made. There was some improvement in neurological and CT findings following radiotherapy and chemotherapy. PMID- 4020451 TI - Pituitary apoplexy in an acromegalic patient during bromocriptine therapy. Case report. AB - The authors report a case of pituitary apoplexy that developed in a patient shortly after bromocriptine therapy was started for a growth hormone-secreting pituitary adenoma. The tumor was associated with visual impairment and ocular palsies, and was treated by transsphenoidal decompression. Although spontaneous tumor necrosis cannot be excluded, a causal role of bromocriptine treatment is suggested. PMID- 4020452 TI - Spontaneous hematomyelia secondary to factor XI deficiency. Case report. AB - A 34-year-old woman with Factor XI deficiency presented with rapidly progressive quadriplegia following a 1-week prodrome of cervical pain. At operation, a spontaneous hematomyelia was evacuated from the C4-6 vertebral level. The pathophysiology of spontaneous hematomyelia is discussed. PMID- 4020453 TI - Postoperative paraplegia with preserved intraoperative somatosensory evoked potentials. Case report. AB - Intraoperative somatosensory evoked potentials (SSEP's) are being used with increasing frequency to monitor neurological function during spinal surgery. The authors report a case of postoperative paraplegia that occurred despite preserved intraoperative SSEP's in an achondroplastic dwarf who underwent correction of a congenital kyphoscoliosis. Surgeons and anesthesiologists involved with SSEP monitoring should be aware that false-negative results may occur with this technique. PMID- 4020455 TI - A self-retaining multipore suction tube. Technical note. AB - A new self-retaining multipore suction tube with three unusual features is described. The features are: 1) multiple 0.5 mm suction openings; 2) a variable suction control; and 3) a device for fixation to a self-retaining retractor. PMID- 4020454 TI - Cerebral gumma. Case report. AB - A case of focal cerebral syphilitic gumma of the right temporal lobe is reported. Angiography showed moderate focal hypervascularity with stretched vessels, and irregularity of the vessel walls. Plain computerized tomography revealed an area of low density that enhanced strongly after intravenous administration of contrast medium. PMID- 4020456 TI - Absent basal cisterns on computerized tomography. PMID- 4020457 TI - Failure of prophylactic barbiturate coma. PMID- 4020458 TI - Vascular compression of the brain stem. PMID- 4020459 TI - Multiple intracranial aneurysms: determining the site of rupture. AB - A retrospective hospital chart and radiograph review was performed of all patients with multiple intracranial aneurysms seen over a 52-month period. Sixty nine patients with a total of 205 aneurysms were studied. Among the patients with aneurysms, the incidence of multiple aneurysms was 33.5%. Multiple aneurysms were much more common in women, with a female to male ratio of 5:1 for all patients and 11:1 for patients with three or more aneurysms. Common locations for multiple aneurysms were the posterior communicating artery (22%), middle cerebral artery (21.5%), anterior communicating artery (12%), and ophthalmic artery (11%). However, locations with the highest probability of rupture were the anterior communicating artery (62%), posterior inferior cerebellar artery (50%), and basilar artery summit (50%). The middle cerebral artery was the least likely site for rupture. In contrast to previous studies, in this series irregularity of contour was more important than size in identifying the site of rupture. Using a simple algorithm outlined in the text, it was possible to identify the site of aneurysm rupture in 97.5% of cases. PMID- 4020460 TI - Subarachnoid hemorrhage of unknown origin: prognosis and prognostic factors. AB - The cases of 127 consecutive patients with subarachnoid hemorrhage (SAH), in whom cerebral panangiography revealed no cause for the bleeding nor any sign of an intraparenchymatous hemorrhage, were reviewed in a study of the long-term prognosis and the possible prognostic factors in this condition. Data for all 127 patients in the study were obtained, with an average follow-up period of 5.4 years. After the 1st week post-SAH, only three rebleeds had occurred. In all, 80% of the patients had returned to full activity, 91% to at least part-time work; if the patients with hypertension were excluded, these figures rose to 86% and 95%, respectively. Decreased wakefulness on admission related to a slightly poorer prognosis, whereas age and red blood cell count in the cerebrospinal fluid had no prognostic significance. Of those patients who, at the end of the 2nd week following the SAH, were fully awake and had not developed any symptoms of delayed cerebral ischemia (87% of all patients admitted), 88% returned to full activity, 97% to at least part-time work. The survival rate for this group, as well as causes of death, seem to be within the range for normal individuals. It should thus be possible to inform these patients (at least the normotensive ones) of the benignity of their condition, directly after normal angiography. Even among the patients who were able to return to full activity, symptoms attributable to the SAH were common: 22% experienced problems such as frequent headaches, vertigo, irritability, and increased fatigability. PMID- 4020461 TI - Acute hydrocephalus after aneurysmal subarachnoid hemorrhage. AB - Hydrocephalus, defined as a bicaudate index above the 95th percentile for age, was found in 34 (20%) of 174 prospectively studied patients with subarachnoid hemorrhage (SAH) who survived the first 24 hours and who underwent computerized tomography (CT) scanning within 72 hours. The occurrence of acute hydrocephalus was related to the presence of intraventricular blood, and not to the extent of cisternal hemorrhage. The level of consciousness was depressed in 30 of the 34 patients. Characteristic clinical features were present in 19 patients, including a gradual obtundation after the initial hemorrhage in 16 patients and small nonreactive pupils in nine patients (all with a Glasgow Coma Scale score of 7 or less). In the remaining 15 patients (44%), the diagnosis could be made only by CT scanning. After 1 month, 20 of the 34 patients had died: six from rebleeding (four after shunting), 11 from cerebral infarction (eight after an initial improvement), and three from other or mixed causes. Only one of nine patients in whom a shunt was placed survived, despite rapid improvement in all immediately after shunting. The mortality rate among patients with acute hydrocephalus was significantly higher than in those without, with the higher incidence caused by cerebral infarction (11 of 34 versus 12 of 140 cases, respectively; p less than 0.001). Death from infarction could not be attributed to the extent of cisternal hemorrhage, the use of antifibrinolytic drugs, or failure to apply surgical drainage, but could often be explained by the development of hyponatremia, probably accompanied by hypovolemia. PMID- 4020462 TI - CT myelography with intramedullary enhancement in cervical spondylosis. AB - The authors describe seven cases of cervical spondylosis in which small high density areas were detected in the spinal cord on delayed computerized tomographic (CT) myelography. These high-density areas are believed to represent cavities or areas of cystic necrosis. In all seven cases the cervical spinal canal was narrow, and the spondylosis was located at multiple levels, causing a so-called "pincer effect." On the CT scans the high-density areas resembled fried eggs in the gray matter. These areas were localized near the abnormal cervical discs. In two cases in which the Brown-Sequard syndrome was noted, the symptoms could be attributed to the morphology of the high-density area on the affected side of the cord. Following decompressive surgery, most of the symptoms improved except for numbness of the upper extremities and motor weakness of hands. PMID- 4020463 TI - Trilateral retinoblastoma: ocular and pineal retinoblastomas. AB - Trilateral retinoblastomas, the syndrome of bilateral retinoblastoma associated with ectopic retinoblastoma in the pineal gland, is rare but well recognized. In contrast to bilateral retinoblastomas alone, the ocular retinoblastomas in trilateral retinoblastoma develop before the age of 6 months, and a family history positive for retinoblastoma is usually obtained. The retinal tumors are often quiescent at the time that the pineal tumor is discovered, and show no evidence of metastatic spread after enucleation of the globes. Pathologically, the pineal tumor is indistinguishable from the ocular retinoblastoma. The pathophysiology of this syndrome is not well understood, but a germinal mutation is thought to target photoreceptor tissue for further postzygotic mutation. Eventual expression depends on the inherited host resistance to the carcinogenic manifestation of these genes. The low host resistance of trilateral retinoblastoma is evident by the early age of presentation, the multicentric occurrence of the tumor, and the high early mortality rate despite aggressive management. PMID- 4020464 TI - Surgical treatment for fungal infections in the central nervous system. AB - The hospital records of 78 patients who underwent surgical therapy for fungal infections of the central nervous system (CNS) between 1964 and 1984 are summarized. Nine different fungal types were identified, but Coccidioides immitis and Cryptococcus neoformans accounted for most (67.1%) of the infections. A variety of clinical syndromes were seen, including chronic basal meningitis (45 patients), intracranial mass lesions (12 patients), and communicating hydrocephalus (six patients). Thirteen patients had rhinocerebral forms of fungal infection, and two presented with spinal involvement. Delays in diagnosis were frequent and ranged from 2 months to 11 years. In 31 patients the CNS lesion was the first indication of a fungal infection, and lesion biopsy or cerebrospinal fluid (CSF) examination confirmed the diagnosis. A total of 144 surgical procedures were carried out, including lesion biopsy or excision in 13 patients, primary CSF shunting in 22, and placement of an Ommaya reservoir for administration of intraventricular or intracisternal antifungal agents in 48. All patients received parenteral and, in some cases, intrathecal or oral antifungal chemotherapy in addition to surgical therapy. Overall mortality was 43.6% (34 deaths). With prompt diagnosis and treatment, the mortality rate was 39% whereas, when appropriate treatment was delayed, the mortality rate was 64%. An additional 14 surviving patients (17.9%) exhibited permanent morbidity due to neurological deficits, seizure disorders, or renal toxicity following treatment with amphotericin B. The combined mortality and morbidity rate was 62.8%. Clinical symptoms were resolved completely in 29 patients, although in 10 evidence of disease persisted and chemotherapy was continued. Fungal infections of the CNS are being recognized with increased frequency. It is suggested that a high index of suspicion, aggressive attempts to obtain a diagnosis, and early and vigorous therapy may reduce the unfortunate outcome seen in a relatively high proportion of patients with CNS fungal infections. PMID- 4020465 TI - Juvenile pilocytic astrocytoma of the cerebrum in adults. A distinctive neoplasm with favorable prognosis. AB - Seven adults (15 years of age or older) with juvenile pilocytic astrocytoma of the cerebrum were treated at Barnes Hospital in St. Louis, Missouri, from 1950 to 1981. This group comprised 7% of the total adult population with well differentiated astrocytoma and astrocytoma with anaplastic foci treated over a 30 year period. All seven patients were less than 30 years old at the time of presentation. The tumors were characterized by distinctive histology, a predilection for the temporal lobe, the presence of a major cyst, and relative gross circumscription making total surgical resection feasible. In contrast to patients with diffusely infiltrating cerebral astrocytoma, those with juvenile pilocytic astrocytoma have had an extremely favorable course, regardless of treatment. Four were treated with surgery alone after total gross tumor excision, and three received postoperative irradiation after subtotal excision. Six were alive 27, 24, 17, 9, 5, and 2 years after initial surgery. One patient died 7 years after surgery and radiation as a result of cerebral radiation necrosis. Juvenile pilocytic astrocytoma of the cerebrum is a recognizable, distinctive entity with natural history and pathological characteristics similar to the relatively benign cerebellar astrocytoma of childhood. PMID- 4020466 TI - Carotid endarterectomy. Review of 150 consecutive cases in two small community hospitals. AB - The authors have reviewed 150 consecutive carotid endarterectomies in 140 patients performed by three neurosurgeons. These were performed in two small community hospitals. There was an overall mortality rate of 1.3%; major or minor stroke was seen in 2.7% of patients and transient neurological dysfunction in 2.7%. Preoperative symptoms included major or minor stroke in 39.3% of patients and transient neurological dysfunction in 43.3%; 17.3% of patients were asymptomatic. The patients were continuously monitored intraoperatively with electroencephalography. There were two operative deaths, both related to myocardial infarction and both on the 2nd postoperative day. These statistics appear to compare favorably with those of series reported by major institutions. The average number of carotid endarterectomies per surgeon per year was 10. These were performed over a 7-year period (October, 1976, through November, 1983). Previous series have implied the need for higher frequency in performing the procedure to assure low morbidity and mortality rates. This series appears to offer evidence to the contrary. A key to these results has been that in 148 of the 150 operations, the primary surgeon has been assisted by one of the other two neurosurgeons. This affords the primary surgeon the benefit of excellent technical assistance, and also broadens the experience of the assisting surgeon, thereby allowing maximum experience from the small volume of cases. PMID- 4020467 TI - Pressure-volume conditions in patients with subarachnoid and/or intraventricular hemorrhage. AB - Pressure-volume conditions were studied in 17 patients with subarachnoid and/or intraventricular hemorrhage, who underwent continuous intracranial pressure (ICP) monitoring. The pressure-volume index (PVI) technique was used. The interrelationship between the ICP pulse amplitude and compliance was also examined. All patients were admitted in Hunt and Hess Grades II to V, and 11 had a proven aneurysm. The ICP was above 15 mm Hg in all patients during some part of the monitoring period. The pressure-volume conditions were abnormal in all patients. Median PVI was 12.7 ml (5.8 to 40.0 ml). The PVI did not correlate with ICP: the PVI based on bolus injection was significantly greater than PVI based on fluid withdrawal. The ICP pulse amplitude varied from 1.5 to 15 mm Hg and rose concomitantly with increasing ICP. Considering the pulsatile shift in intracranial blood volume as an endogenous bolus that increases ICP from the diastolic (Pdiast) to the systolic (Psyst) level, an equation was derived from the PVI model that describes the relationship between the Psyst:Pdiast ratio and the PVI. PMID- 4020468 TI - Fluid balance and secretion of antidiuretic hormone following transsphenoidal pituitary surgery. A preliminary series. AB - Hyponatremia developing some days after transsphenoidal pituitary adenectomy is a treacherous complication of uncertain cause. Of 19 patients monitored in a pilot study at the Wessex Neurological Centre, plasma sodium fell below 125 mmol/liter in three patients at times ranging from 6 to 9 days postoperatively. One patient had evidence of inappropriate secretion of arginine vasopressin (AVP), and the other two probably had steroid insufficiency despite apparently adequate steroid cover. In a more detailed study, the fluid and sodium balance of a further 16 patients was monitored for 7 to 11 days following transsphenoidal surgery together with plasma cortisol, renin, and AVP concentrations. No patient became severely hyponatremic. Three developed partial diabetes insipidus. Two patients with Cushing's disease had evidence of postoperative corticosteroid insufficiency despite normal steroid protection. An inappropriately low plasma cortisol concentration was recorded in both. Plasma AVP concentrations did not show a delayed surge postoperatively. Delayed hyponatremia appears to occur most often in patients with hypoadrenalism, as glucocorticoid cover is decreased. It results from water retention combined with natriuresis, and is reversed by glucocorticoid treatment. PMID- 4020469 TI - S-100 protein and calmodulin levels in cerebrospinal fluid after subarachnoid hemorrhage. AB - The levels of two calcium-binding proteins, S-100 protein and calmodulin, were measured serially in the cerebrospinal fluid (CSF) of patients after subarachnoid hemorrhage (SAH) and aneurysm surgery. These two proteins have a similar molecular structure and are highly concentrated in the central nervous system (CNS). The levels of S-100 protein found in the earliest postoperative CSF samples correlated with the preoperative SAH grades. High S-100 protein levels in the CSF were found in patients with poor SAH grades. Moreover, the prognosis of the patients correlated with the S-100 protein levels in the CSF samples taken during the immediate postoperative period and with the daily changes of the S-100 protein levels. Severe diffuse cerebral vasospasm was followed by a sharp S-100 protein increase. These results suggest that S-100 protein levels in the CSF provide a useful index of organic damage in the CNS, and furthermore that S-100 protein levels and their changes may have prognostic value for patients after SAH. On the other hand, there was a lack of correlation between the calmodulin levels and the preoperative grade or outcome. It would be inappropriate, however, to speculate from the results of this study that these calcium-binding proteins in the CSF play any causative role in pathological processes such as cerebral vasospasm or brain ischemia after SAH, since changes in the levels of these proteins followed the onset of clinical signs of deterioration. PMID- 4020470 TI - Morphological studies of human arteriovenous malformations. Effects of isobutyl 2 cyanoacrylate embolization. AB - Ten patients with symptomatic arteriovenous malformations (AVM's) underwent embolization with isobutyl 2-cyanoacrylate (Bucrylate) delivered via a mini balloon catheter according to the protocol of George and Pevsner. These patients underwent surgical removal of their embolized AVM, and surgical specimens were evaluated by light and scanning electron microscopy. Ten other patients with AVM's underwent surgical resection without prior embolization, and these surgical specimens were evaluated in a similar manner. Results from this study indicate that Bucrylate incites an inflammatory response characterized by foreign-body giant cells. This reaction was present as early as 3 weeks after embolization and persisted in specimens resected almost 1 year after the last embolization. No such reaction was observed in unembolized AVM's. Both light and scanning electron microscopy demonstrated a lattice structure of the Bucrylate embolus within the AVM vessels. These studies also demonstrated micro-channels within the Bucrylate embolus and the presence of what appears to be normal red blood cells within the latticework of the embolus. Vascular endothelium not in direct contact with the Bucrylate embolus retains a normal morphology as revealed by scanning electron microscopy. PMID- 4020471 TI - Stem cell studies of human malignant brain tumors. Part 2: Proliferation kinetics of brain-tumor cells in vitro in early-passage cultures. AB - The proliferation kinetics were studied in early-passage cultures of cells from 13 human malignant brain tumors and two specimens of normal brain under conditions similar to those used in clonogenic cell-survival studies. Autoradiography was performed in all but four cases to estimate the fraction of cells actively replicating deoxyribonucleic acid (DNA), the approximate cell cycle time, and the effect of low-dose tritiated thymidine on cell proliferation. The mean tumor cell doubling time (TD) was 53 hours for five glioblastomas, 46 hours for two ependymomas, and 83 hours for two medulloblastomas. A gliosarcoma grew fastest (TD = 22 hours) in culture and a pilocytic astrocytoma grew slowest (TD = 144 hours). The approximate cell cycle time ranged from 1 to 2.5 days for all tumors tested. This suggests that chemotherapeutic agents that predominantly kill proliferating cells should be administered in vitro for at least 2 to 2.5 days to achieve maximum cell kill. The approximate growth fraction ranged from 0.65 to 0.96 for all tumors except for the two medulloblastomas and the pilocytic astrocytoma, which had growth fractions of 0.34 and 0.35, respectively. Most laboratories investigating the chemosensitivity of primary or early-passage human tumor cells require that 40% to 70% of cells be killed to consider a drug active in vitro. The results of this study suggest that the cell-cycle-specific agents cannot achieve a high enough cell kill to be considered active for some tumors that grow slowly in culture. An estimate of the in vitro growth rate is necessary to reliably interpret cell-survival results with such agents. Tritiated thymidine appeared to slow cell proliferation in some of the cultures, presumably as a result of radiation-induced DNA damage caused by tritium that had been incorporated into DNA. The degree to which cell growth ws slowed in individual tumors correlated with the patient's clinical response to radiation therapy and postoperative survival time. PMID- 4020472 TI - Barrier disruption in the major cerebral arteries following experimental subarachnoid hemorrhage. AB - The effects of experimental subarachnoid hemorrhage (SAH) on the blood-arterial wall barrier in the major cerebral arteries were studied in 20 normotensive dogs. Horseradish peroxidase (HRP) was given intravenously before the animals were sacrificed to assess the integrity of the barrier. Transient elevation of intracranial pressure (ICP) produced by cisternal injection of saline solution resulted in HRP leakage at the branching points of the major cerebral arteries. Extensive disturbance of the blood-arterial wall barrier was consistently observed in the major cerebral arteries after SAH, with or without elevation of ICP. These results suggest that both subarachnoid clot and a sudden rise in the ICP are important factors causing the breakdown of the blood-arterial wall barrier, but that the effect of the clot is the most profound. Electron microscopy revealed that opening of the interendothelial junctions is one of the important mechanisms responsible for the HRP leakage in the major cerebral arteries following SAH. Disturbance of arterial permeability in the major cerebral arteries following SAH probably accounts for the abnormal post-contrast enhancement that occurs in patients who are prone to develop vasospasm following aneurysm rupture, and is probably involved in the pathogenesis of vasospasm. PMID- 4020473 TI - Vicryl (polyglactin 910) mesh as a dural substitute. AB - Many substances have been used as dural substitutes. Although the various materials are effective in a variety of settings, a material that is absorbed over time, elicits minimal inflammatory reaction, is relatively inexpensive, and is easily manipulated would be beneficial. An experimental project was conducted involving closure of dural defects in dogs with a Vicryl (polyglactin 910) mesh graft. Macroscopic and histological examination performed at various times after placement revealed resorption of the graft material, little cerebromembranous adhesion formation, and complete lack of injury to subjacent cortical zones. A substantial neomembrane forms over the zone of the mesh graft. The authors suggest that Vicryl mesh has significant potential as an absorbable, minimally reactive dural substitute. PMID- 4020474 TI - Spinal intramedullary pseudocyst. Case report. AB - The authors describe a case of a spinal intramedullary pseudocyst at T-1 that did not communicate with the surrounding spaces. The cystic wall was composed of dense connective tissue without epithelial or neoplastic cells. The patient's condition improved dramatically after surgical removal of the cyst. The literature on spinal intramedullary cystic lesions is reviewed and the etiology of pseudocysts is discussed. This case is believed to be the first in which a pseudocyst has been demonstrated within the spinal cord. PMID- 4020475 TI - Unusual delayed onset of diabetes insipidus following closed head trauma. Case report. AB - A case of delayed onset of diabetes insipidus (DI), which developed 27 days after a closed head injury, is reported. The patient sustained only a minor neurological deficit and, except for antidiuretic hormone (ADH) insufficiency, hypothalamic function was intact. This selective damage of posterior pituitary function was total and permanent. Ischemia due to vascular injury may be the most likely etiology. Once the diagnosis of delayed posttraumatic DI is confirmed, the treatment of choice is DDAVP (desmopressin acetate). In contradistinction to DI immediately following minor head injury, most patients with a delayed onset of DI after trauma have permanent ADH deficiency. PMID- 4020476 TI - Ventriculoperitoneal shunt malfunction during pregnancy. Case report. AB - Malfunction of a ventriculoperitoneal shunt is reported in a 25-year-old woman at 32 weeks of gestation. Pregnancies and delivery in women with cerebrospinal fluid shunts are rarely reported, and malfunction of a shunt system during pregnancy is extremely unusual. PMID- 4020477 TI - Fibrosis surrounding a silicone implant simulating recurrent orbital meningioma. Case report. AB - A patient with the preoperative diagnosis of recurrent orbital apical meningioma was found to have a fibrotic capsule surrounding a silicone plate implanted 3 years previously to reconstruct the orbital roof. Caution is urged in using alloplastic orbital implants for reconstructive purposes in patients undergoing orbital surgery, because associated fibrous capsule formation may mimic tumor recurrence. PMID- 4020478 TI - Electron microscopic diagnosis of cerebral toxoplasmosis. Case report. AB - Rapid and specific diagnosis of infections involving patients with acquired immunodeficiency syndrome (AIDS) is imperative. Toxoplasmosis is one of the most frequent causes of central nervous system disease in these patients. The authors present a case of cerebral toxoplasmosis in an AIDS patient, diagnosed by electron microscopy of brain biopsy tissue using rapid techniques. PMID- 4020479 TI - Brain targets in Parkinson's disease surgery. PMID- 4020480 TI - Fourth ventriculoceles with extracranial extension. PMID- 4020481 TI - Influence of undernutrition during gestation and suckling on development and sexual maturity in the rat. AB - The effects of undernourishment during gestation and suckling on rats subsequently fed ad libitum for 4 mo after weaning are explored. We measured the following: weight at birth and over a 5-mo period; sexual behavior of adult males; curiosity; basal physical activity; morphometric measures; organ weights (absolute and relative) including brain, testicles and seminal vesicles in males 5 mo of age; and the O2 uptake of some brain and glandular structures in males at 5 mo of age. Body weight of the malnourished animals was consistently lower than that of the controls. Compared to controls sexual behavior in undernourished males was significantly reduced, while curiosity test and basal physical activity were increased. The absolute weights of all organs (except the pituitary gland) were significantly lower in malnourished males at 5 mo than in controls. Compared to controls, relative weight of brain was greater and that of seminal vesicles was less in the male rats. Oxygen uptake was significantly lower in the pituitary gland and testicles of malnourished males than of controls. In view of these results, it can be concluded that malnutrition in utero and while suckling affects fundamental parameters of both development and reproductive function in the male offspring 4 mo after feeding ad libitum is begun at weaning. PMID- 4020482 TI - Vitamin A during lactation: relationship of maternal diet to milk vitamin A content and to the vitamin A status of lactating rats and their pups. AB - We have investigated the effects of maternal vitamin A intake during pregnancy and lactation or during lactation alone on the concentration of vitamin A in rat's milk and on vitamin A levels in plasma and liver of dams and their pups. Groups of Sprague-Dawley rats were fed diets having either a high vitamin A content [15 retinol equivalents (R.E.)/g diet] or a low vitamin A content (0.6 R.E./g) for 42 d, including 7-8 d prior to pregnancy, pregnancy, and for 14 d of lactation. The concentration of vitamin A in milk on d 14 of lactation was significantly greater on the high vitamin A diets [114 +/- 16 micrograms/dl (mean +/- SEM; n = 8) versus 52 +/- 7.3 micrograms/dl (n = 11), P less than 0.005]. However, milk vitamin A concentration on d 1 of lactation did not vary with maternal vitamin A intake during pregnancy. In a second study in which supplementation with vitamin A (30 R.E./g diet) was begun on d 1 postpartum, the milk vitamin A content increased progressively with duration of lactation. Maternal plasma vitamin A concentrations did not differ between rats fed the higher or lower vitamin A diets. However, liver vitamin A concentrations both of dams and of their 14-d-old pups were significantly higher when dams were fed the higher vitamin A diets during pregnancy and/or lactation. The results of these studies indicate that the transfer of vitamin A from mother to offspring by milk and the vitamin A status of dams and their suckling neonates is influenced by maternal vitamin A intake during lactation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4020483 TI - Availability to rats of iron in ferric hydroxide polymers. AB - Availability to rats of Fe in isolated ferric hydroxide polymers was assessed. Polymers were prepared by hydrolyzing an 59Fe-labeled ferric nitrate solution with base (KHCO3). After isolation by gel filtration, the polymers were characterized by spectrophotometric, dialysis, and ultracentrifugation methods. In a split-plot design experiment, Fe-adequate (Hb 11.4-14.0 g/dl) or Fe deficient (Hb 4.7-9.6 g/dl) male Sprague-Dawley rats (10/treatment) were dosed by stomach tube with one of the following 59Fe-labeled solutions: polymers, Fe(NO3)3 (low-molecular-weight control), polymers + citrate, or Fe(NO3)3 + citrate. As expected, Fe-deficient animals absorbed more Fe than adequate animals (P less than 0.01). There was no difference in absorption of Fe between polymers and low molecular-weight control doses (P greater than 0.05). In Fe-adequate animals, citrate significantly depressed the uptake of Fe both from Fe(NO3)3 and polymers. These results indicate 1) that polymerization of Fe species prior to ingestion is not a likely means by which Fe is rendered unavailable and 2) that the effect of citrate on Fe absorption may depend on the Fe status of the animal. PMID- 4020484 TI - Effects of protein deficiency and food restriction on lung ascorbic acid and glutathione in rats exposed to ozone. AB - Weanling (52 +/- 4 g) or adult (259 +/- 16 g) male Sprague-Dawley rats were fed ad libitum casein-based diets containing 4 or 16% protein. A third group (food restricted) was fed daily the 16% protein diet, but at the food intake level of the 4% protein group. After 3 wk (weanling) or 5 wk (adults), half of the rats in each group were continuously exposed to 0.64 ppm ozone for 7 d. Ascorbic acid and reduced glutathione levels were then measured. In the heart and liver from weanling rats, ascorbic acid concentrations were lower in the protein-deficient group than in either control group. In the liver from weanling rats glutathione concentrations were also reduced in response to protein deficiency. Exposure to ozone produced no additional response. For adult rats the response for liver glutathione was similar to that of the weanlings. The liver ascorbate concentration, however, was consistently lower in adult rats compared to weanlings exposed to ozone. In lungs from adult rats, the ascorbic acid concentration was lower in the protein-deficient group than in either control group. On a whole-organ basis, both ascorbic acid and glutathione were usually higher in lungs from rats exposed to ozone than from those exposed to air. Interestingly, protein deficiency did not appear to compromise the lung's ability to maintain, in relative terms, the ascorbic acid or glutathione concentration in response to ozone. PMID- 4020485 TI - Skeletal muscle protein turnover in young male pigs. AB - A 6-h continuous infusion of L-[U-14C]tyrosine was used to estimate fractional protein synthesis rates (FSR) in the longissimus dorsi (LD), semitendinosus (ST) and brachialis (BR) muscles of intact male pigs weighing 22 or 45 kg. The FSR was approximately 20% lower for pigs at 45 kg (4.2 vs. 5.2%/d, 5.2 vs. 6.4%/d and 5.1 vs. 6.4%/d for the LD, ST and BR muscles, respectively) compared with pigs at 22 kg. Fractional protein accretion or growth rates (FGR) were estimated over a 2-wk period. At 22 kg, FGR for the LD, ST and BR were 0.7, 2.4 and 1.7%/d, respectively; at 45 kg, FGR for these muscles were 1.7, 1.9 and 0.7%/d. Fractional protein breakdown rates (FBR) derived by difference (FBR = FSR - FGR) were 44, 16 and 8% lower for the LD, ST and BR muscles, respectively, at 45 kg compared with those at 22 kg. Therefore, it is suggested that muscle growth rate is modulated by alterations in FBR. By using the fractional rates found in these muscles to determine total-muscle protein synthesized or degraded in pigs at 22 and 45 kg, the proportion of protein retained was approximately 28% of that synthesized by the pigs at each weight. Since individual skeletal muscles of the pigs differed in protein turnover rates during postnatal growth and development, selection of a muscle(s) for turnover rates in growth studies is critical. PMID- 4020486 TI - Zinc content of blood cellular components and lymph node and spleen lymphocytes in severely zinc-deficient rats. AB - Several investigators have suggested that the measurement of leukocyte zinc may be useful for the assessment of zinc nutriture. However, in an earlier study, we found that the methods used did not adequately separate platelets from the different leukocyte populations. We subsequently developed a method which does adequately separate platelets, mononucleated cells (MNC), polymorphonucleated cells (PMN), and erythrocytes (RBC) from a single blood sample. This method was applied to a study of severe zinc deficiency in adult male rats. Significant reductions in plasma and femur zinc indicated severe zinc deficiency in the zinc deficient animals compared with pair-fed or ad libitum-fed control rats in two separate experiments. However, we noted no differences in the zinc content of the MNC, PMN, RBC or lymph node lymphocytes, on a per cell basis, between the zinc deficient and ad libitum- or pair-fed control groups of rats. A minor, but not significant (P greater than 0.05) reduction of platelet zinc was noted in zinc deficient rats in two separate studies. These data indicate that the zinc contents of blood cellular components are not sensitive indicators of zinc deficiency in rats. PMID- 4020487 TI - Uptake of pyridoxine by in vivo perfused segments of rat small intestine: a possible role for intracellular vitamin metabolism. AB - The present studies utilized the in vivo single-pass, luminally perfused intestinal segment model in rats to evaluate pyridoxine (PN) uptake under conditions that permitted prolonged exposure of mucosa to relatively constant PN concentrations. Perfusates contained [14C]PN, unlabeled PN, and [3H]polyethylene glycol in buffer. Uptake was constant for 1 h and correlated with water absorption. Uptake of 0.2 microM PN was highest in the duodenum, intermediate in the jejunum, and lowest in the ileum. When expressed as uptake/micromolar PN, uptake of 1 mM compared to 0.2 microM PN was decreased by 37.5% in duodenum (P less than 0.001) and 14.4% in jejunum (P less than 0.05); uptake/micromolar PN were similar in ileum. In duodenum saturable uptake was apparent for 2-100 microM PN and was not explainable by a membrane carrier, presence of bile or lumen plasma concentration gradients. Conclusions were: 1) uptake of PN by in vivo perfused intestinal segments decreases from proximal to distal; 2) the greater uptake proximally was associated with a saturable component of uptake that was greatest in duodenum, less, but significant, in proximal jejunum and absent in distal ileum and 3) saturation of uptake in the rat proximal small intestine was compatible with a role for mucosal metabolism of absorbed PN in the enhancement of uptake of PN at low luminal concentrations. PMID- 4020488 TI - Effect of ambient temperature on the energy requirements of the lactating rat. AB - The effect of ambient temperature on the energy requirements of the lactating rat was investigated. Ambient temperature was maintained at 13, 20 or 25 degrees C during lactation, and digestible energy (DE) intake, milk output and energy balance were measured between 4 and 12 d post partum. Ambient temperature did not significantly affect DE intake. Milk output was highest in the rats housed at 13 degrees C and lowest in those kept at 25 degrees C, although the rate of body fat mobilization was lowest in the rats kept at 20 degrees C and highest in the rats kept at 25 degrees C. Energy expenditure on activity and maintenance, determined from the difference between DE intake and body nutrient mobilization plus the energy used for milk production, was significantly higher in the rats housed at 25 degrees C than in those kept at 13 degrees C. This is an opposite trend to that which occurs in nonlactating rats. The results indicate that the gross efficiency of energy utilization during lactation is higher at 13 degrees C than it is at 25 degrees C in the rat. PMID- 4020489 TI - Effect of dietary picolinic acid on the metabolism of exogenous and endogenous zinc in the rat. AB - The excretion of 65Zn was compared by metabolic balance studies in adult male rats fed purified diets containing 0.8 mmol Zn/kg diet, with and without 40 mmol picolinic acid per kilogram diet, after single intragastric (i.g.) and intraperitoneal (i.p.) doses of the isotope. In a third experiment picolinic acid was introduced for 3 d into the diet of rats prelabeled with 65Zn. The urinary excretion of total zinc was increased by the ingestion of picolinic acid in all three experiments. The urinary and fecal outputs of 65Zn were both consistently greater in picolinic acid-fed rats than in the corresponding control animals. This was particularly marked after i.p. injection of the tracer, and the specific activities of urine and feces from the treated rats were both increased. When picolinic acid was introduced into the diet of prelabeled rats there was a delay of 24 h in the urinary response and 48 h in the fecal response. The residual 65Zn levels were reduced in several tissues from the picolinic acid-fed rats, especially after i.p. administration of the isotope. These observations indicate that dietary picolinic acid increases the turnover of endogenous zinc in addition to enhancing the absorption and excretion of ingested metal, and this has implications for its use in cases of zinc deficiency. PMID- 4020490 TI - Effect of castration on the metabolism of L-ascorbic acid in rat prostate. AB - An appreciable decrease in the contents of prostatic ascorbic acid and dehydroascorbic acid along with an increase in diketogulonic acid was seen in rats ten days after castration. Castration caused a decrease in the activities of such biosynthetic enzymes as L-gulono-gamma-lactone oxidase and D glucuronolactone-delta-hydrolase with no significant alteration in the activity of L-gulono-gamma-lactone hydrolase in the rat prostate. The activity of dehydroascorbatase, one of the degrading enzymes was, however, found to be elevated in castration. The implication of these results has been discussed. PMID- 4020491 TI - Dietary sulfur-containing amino acids and glycine as determinant factors in plasma cholesterol regulation in growing rats. PMID- 4020492 TI - Histopathological study on rats fed iodine-enriched eggs long-term (7 and 19 months). AB - A histopathological study was conducted on rats fed on a diet containing iodine enriched eggs over the long term, 7 and 19 months. A laboratory powder chow was added at the 1% (w/w) level with ordinary egg powder (ordinary egg diet as control: 35 micrograms iodine/100 g diet) or iodine-enriched egg powder (iodine enriched egg diet: 392 micrograms iodine/100 g diet). The animals were meal-fed twice a day and allowed unrestricted voluntary wheel-running. In general, organs, tissues and endocrine glands including thyroid glands from rats of the iodine enriched egg diet group exhibited no significant difference in histopathological features as compared with those of the ordinary egg diet group. These results suggest that long-term feeding of a considerable amount of iodine through an iodine-enriched egg diet did not cause any specific excess-iodine toxicity. PMID- 4020493 TI - Utilization and requirement of egg protein in Japanese women. AB - Utilization and requirement of egg protein in Japanese women with two levels of energy intake were estimated. In experiment 1, fifteen female students were given semi-purified diet containing whole egg as the sole nitrogen source for 12 days. Nitrogen intakes were 50 for five, 75 for two and 100 mg N/kg for eight subjects. Habitual energy intake was determined individually by detailed inquiry about the foods consumed before the experiment was started. Mean energy intake was 33 kcal/kg. In experiment 2, eighteen other subjects were given the same diet containing four intake levels of egg protein (30, 50, 75, 100 mg N/kg) with an energy intake of about 100 kcal/day added to that calculated by the food intake inquiry. The mean energy intake was 37 kcal/kg. The total nitrogen contents of the experimental diet, urine and feces were analyzed and the nitrogen balance was estimated from these figures. Significant rectilinear relations were found between nitrogen intake (X, mg N/kg) and balance (Y, mg N/kg). The regression equations were: Experiment 1: Y = 0.256X - 34.4 (n = 15, r = 0.742) Experiment 2: Y = 0.326X - 29.7 (n = 18, r = 0.645) The maintenance intakes of whole egg protein for apparent nitrogen equilibrium were calculated to be 134 and 91 mg N/kg with energy intakes of 33 and 37 kcal/kg, respectively. Net protein utilization (NPU) and digestibility of egg protein were calculated using the obligatory N losses previously determined in Japanese women. The NPUs at the maintenance level of egg protein with energy intakes of 33 and 37 kcal/kg were estimated as 31 and 47, respectively. The mean digestibility of egg protein was 96%. PMID- 4020494 TI - Fractionation of Kintoki bean lectin into isolectins. AB - A comprehensive study of the preparative procedure of Kintoki bean lectin resulted in the resolution of the lectin into four isolectins whose pIs varied from 5.19 to 5.67. They agglutinated human, goat, hen and mouse erythrocytes, but not those of cow. The more acidic the isolectins, the less active were the erythrocyte agglutination and the more active the stimulation of sheep lymphocytes. Although the general patterns of amino acid composition were similar, characterized by higher contents of aspartic acid, leucine and valine and lack of sulfur-containing amino acids, differences were found in a few amino acids such as phenylalanine, valine and lysine. Each lectin seems to be a tetramer of a 33,000 dalton subunit which is thought to differ in charge from lectin to lectin. PMID- 4020495 TI - Gasoline exposure, smoking, and kidney cancer. PMID- 4020496 TI - Brain tumors at a nuclear facility. PMID- 4020497 TI - Misconception concerning the ubiquitous p value. PMID- 4020498 TI - Part-time employment and women's health. AB - The relationships between part-time employment and self-reported health are analyzed for a national probability sample of middle-aged women. Overall, there was a tendency for full-time workers to have the best health, part-time workers to have an intermediate level of health, and women who were not in the labor force to have the poorest health. However, the pattern varied by race and marital status. For married black women, part-time workers reported poorer health than full-time workers. This appeared to be due in part to the lower socioeconomic status of the black part-time workers. For married white women, there was little or no difference in health or socioeconomic status between part-time and full time workers. Additional hypotheses and relevant evidence are presented. PMID- 4020499 TI - Occupational exposure to electromagnetic fields and the occurrence of brain tumors. An analysis of possible associations. AB - To explore the association between occupation and the occurrence of brain tumor, an epidemiologic study was conducted using data from the death certificates of 951 adult white male Maryland residents who died of brain tumor during the period 1969 through 1982. Compared with the controls, men employed in electricity related occupations, such as electrician, electric or electronic engineer, and utility company serviceman, were found to experience a significantly higher proportion of primary brain tumors. An increase in the odds ratio for brain tumor was found to be positively related to electromagnetic (EM) field exposure levels. Furthermore, the mean age at death was found to be significantly younger among cases in the presumed high EM-exposure group. These findings suggest that EM exposure may be associated with the pathogenesis of brain tumors, particularly in the promoting stage. PMID- 4020500 TI - Obtaining occupational exposure histories in epidemiologic case-control studies. AB - In a large population-based case-control study designed to generate hypotheses regarding possible associations between cancer sites and occupational exposures, an innovative methodology is utilized to infer the subjects' chemical exposures. It features (1) a probing interview to obtain a detailed portrait of each job the subject has held, (2) exposure coding by a team of chemists and hygienists who review each interview, (3) a coding checklist of nearly 300 occupational exposures including the most common ones, and (4) indication by the coders of the level, frequency, and mode of exposure, as well as of their degree of confidence that the exposure occurred. In making coding decisions, the chemists draw upon their experience and upon consultants and bibliographic sources. Resultant data can be combined to produce a variety of semi-quantitative indices of exposure for epidemiologic analyses. PMID- 4020501 TI - Maternal employment and the chromosomal characteristics of spontaneously aborted conceptions. AB - The employment histories of 1,252 women experiencing a spontaneous abortion and 2,126 controls were compared to examine the relation between maternal employment before and during pregnancy and karyotype of the spontaneously aborted conceptus. Among private patients, there was no evidence of a positive association of work only before pregnancy, only during pregnancy, or both before and during pregnancy (v no work) with either chromosomally normal or abnormal abortions. In contrast, among public patients the odds of working only during pregnancy or both before and during pregnancy were raised for chromosomally abnormal abortions (adjusted odds ratios = 3.11 and 1.86, respectively) and slightly raised for chromosomally normal abortions (adjusted odds ratios = 1.35 and 1.31, respectively). Among workers, the frequencies of work before pregnancy in specific employment circumstances were compared among karyotyped cases and controls. For two work locations--factory and hospital/nursing facility--the data were of sufficient size to suggest that associations of twofold or greater with most types of abortion are unlikely. PMID- 4020502 TI - Population-based occupational cancer incidence surveillance. Utilization of the telephone interview. AB - Because population-based surveillance of cancer incidence across a wide variety of industries and occupations is quite rare and because the vast literature in occupational cancer epidemiology concentrates to a great extent on cancer risks among white males, new methods are needed to generate hypotheses about occupational cancer risks. The results of a series of studies conducted during the past six years suggested that the telephone interview could be utilized as an effective method for occupational cancer surveillance. A 10-minute telephone interview that was developed to collect occupational histories, smoking histories, and other related data and some methodologic issues that were tested during a pilot study are described. The authors found the telephone interview to be an effective instrument for obtaining these data. This study suggests that it is important to obtain as high a proportion as possible of the responses from the study patients rather than proxy respondents; that when one cannot interview the patient, proxy respondents can provide much of the data requested; and that supplementing population-based cancer surveillance system data with these interview data is useful in routine monitoring. PMID- 4020503 TI - Texaco mortality study. I. Mortality among refinery, petrochemical, and research workers. AB - The Texaco mortality study is a retrospective follow-up study of all persons who were employed for at least five years in a refining, petrochemical, or research facility and who worked at some time during the period 1947 through 1977. Of the 19,077 white men in the cohort, 14,609 were alive, 4,024 were known to be dead, and the vital status of the remaining 444 was unknown as of Dec. 31, 1977. The standardized mortality ratio (SMR) of 75 for all causes was significantly low, on the basis of 5,332 expected deaths. Statistically significant deficits also were seen for all major causes of death and for cancer of many sites, including lung, stomach, bladder, and colon. The SMR was greater than 100 for six causes of death: pancreas cancer, brain cancer, leukemia, Hodgkin's disease, other lymphatic cancer, and benign neoplasms. However, none of these increases was statistically significant, and all SMRs except that for benign neoplasms (SMR = 148) were under 119. PMID- 4020504 TI - Reproductive variables as possible confounders in occupational studies of breast and ovarian cancer in females. AB - In a study of occupational mortality among all females dying at age 20 years or over in British Columbia during the period 1950 through 1978, significantly elevated proportional mortality ratios (PMRs) were seen for breast and/or ovarian cancer among teachers, nurses, office clerks, and sales clerks. Approximately 91% of the female deaths were recorded as occurring among "homemakers." When the PMRs were recalculated for "working women" only (ie., excluding homemakers), most of the excesses in risks for breast and ovarian cancer observed among the four occupational groups disappeared. The authors suggest that the differences in PMR values between all women and working women are due to protective higher parity and lower maternal age at first birth among homemakers as opposed to working women in general. In occupational studies of hormone-related tumors among women, every effort should be made to control for parity level and maternal age at first birth. PMID- 4020505 TI - Congenital anomalies and paternal occupational exposure to shortwave, microwave, infrared, and acoustic radiation. PMID- 4020506 TI - Visibility of interference fringes near the resolution limit. AB - The contrast sensitivity of the visual system to interference fringes has been measured in the range from 10 to 65 cycles/deg with a forced-choice psychophysical procedure. Masking produced by the spatial-noise characteristic of coherent fields was avoided by diluting the interferometric field with a fixed amount of uniform, incoherent light. The loss of contrast sensitivity between 10 and 60 cycles/deg ranged from 0.85 to 1.5 log units depending on the observer. Despite these individual differences, the mean contrast sensitivity for six observers at 60 cycles/deg was more than a factor of 8 higher than the most sensitive previous estimates, suggesting that the neural visual system is much more sensitive to fine detail than previously believed. The most sensitive observer required only 4% contrast to detect a 60-cycle/deg interference fringe. Even the shallow interferometric contrast-sensitivity functions reported here are too steep to be explained solely by scattered light at the retina. It is argued that the optical properties of the photoreceptor mosaic make a negligible contribution to the contrast-sensitivity loss between 0 and 60 cycles/deg, and neural factors must be implicated. PMID- 4020507 TI - Spatial pattern as a stimulus to the pupillary system. AB - Pupillary responses to the contrast reversal of a checkerboard pattern of variable check size and contrast were measured. The results show that the pupillary system is responsive to the contrast reversal. It is argued that this response is the light reflex caused by the local luminance change. The summation characteristics of the pupillary afferent are considered. It has also been found that the pupil size, without any influence from contrast reversal, systematically changes with the changes in the check size. Whether this pupillary change is caused by the variation in accommodative performance with changing spatial factors of visual stimulus is discussed. PMID- 4020508 TI - Periodicity of striate-cortex-cell receptive fields. AB - If striate cells had the simple bipartite or tripartite receptive fields (RF's) classically attributed to them, they should be quite broadly tuned for spatial frequency. Most striate-cortex cells, however, are fairly narrowly tuned and would be expected to have more-periodic RF's. We have examined this question in recordings of the responses of cat and monkey striate-cortex cells to gratings of increasingly large number of cycles, all centered on the cells' RF's. Simple cells narrowly tuned for spatial frequency were found to increase their responses with increasing numbers of stimulus cycles beyond the 1 1/2 cycles expected from the classical RF shape. Broadly tuned simple cells were found to have less periodic RF's. Whereas narrowly tuned complex cells were also found to respond maximally to many stimulus cycles, other more broadly tuned complex cells did as well (possibly reflecting summation across many broadly tuned simple cells without regard to phase). A suppressive region was often seen just outside the excitatory two-dimensional spatial-frequency region, at off orientations and/or off spatial frequencies and around the whole RF in space. Most striate cells can thus be described as having periodic RF's in the space domain such that they fire just to patterns whose local spatial-frequency spectra fall within a compact, restricted, roughly circular two-dimensional spatial-frequency region, with an encircling suppressive region in both the space and the frequency domains. PMID- 4020509 TI - Relationship between spatial-frequency and orientation tuning of striate-cortex cells. AB - If striate cells had the receptive-field (RF) shapes classically attributed to them, their preferred spatial frequencies would vary considerably with orientation. Other models of RF shape would predict a greater independence between orientation and spatial-frequency tuning. We have examined this by recording the responses of cat striate-cortex cells to a wide range of different spatial-frequency and orientation combinations. In almost all cells studied, peak orientation did not consistently vary with spatial frequency, but the majority of cells showed some change in peak spatial-frequency tuning with orientation. The amount of change in peak spatial frequency tended to be greater for cells that were narrowly tuned for orientation. However, cells narrowly (and also very broadly) tuned for spatial frequency tended to show considerable independence of spatial-frequency and orientation tuning, and in all but a few cells the degree of change was less than predicted by the classic RF model. Such cells were found to fire only to patterns whose local spatial spectra fell within a compact, restricted, roughly circular two-dimensional spatial-frequency region. We conclude that the two-dimensional RF shape of striate cells more closely approximates that predicted by a two-dimensional Gabor model or by a Gaussian derivative model than it does the classic shape based on the output of geniculate cells with aligned RF's. PMID- 4020510 TI - Equivalent-noise model for contrast detection and discrimination. AB - Models for the detection and the discrimination of low-contrast signals by human observers typically assume that the observer is limited by the filtering action of the visual system and by the noisy character of its processing. For some models both the filtering and the noise can be represented by a noise in the stimulus domain, the input equivalent noise of the model. We derive some formulas for computing this noise, describe the calculation of a sample, and discuss some implications of this approach. PMID- 4020511 TI - Spatial-frequency spectrum of patterns changes the visibility of spatial-phase differences. AB - This study showed that spatial-frequency components over a 4-octave range affected the visibility of spatial-phase differences. Contrast thresholds were measured for discrimination between two (+45- and -45-deg) spatial phases of a sinusoidal test grating added to a background grating. The background could contain one or several sinusoidal components, all in 0-deg phase. Phase differences between the test and the background were visible at lower constrasts (1) when test and background frequencies were harmonically related than when they were not, (2) when test and background frequencies were within 1 octave than when they were farther apart, (3) when the fundamental frequency of the background was low than when it was high, and (4) for some discriminations more than for others, after practice. The visibility of phase differences was not affected by additional components in the background if the fundamental and difference frequencies of the background remained unchanged. Observers' reports of their strategies gave information about the types of attentive processing that were used to discriminate phase differences. Attentive processing facilitated phase discrimination for multifrequency gratings spanning a much wider range of spatial frequencies than would be possible by using only local preattentive processing. These results were consistent with the visibility of phase differences being processed by some combination of even- and odd-symmetric simple cells tuned to a wide range of different spatial frequencies. PMID- 4020512 TI - Masking of spatial-frequency discrimination. AB - Spatial-frequency discrimination thresholds were measured using the temporal two alternative forced-choice procedure. A superimposed masker grating reduced discrimination threshold more than 20-fold when the spatial frequency of the masker was close to the test spatial frequency because moire fringes provided a sensitive cue to the test grating's spatial frequency. When the effectiveness of this cue was reduced by randomly changing the frequency of the masker grating on successive presentations, masked thresholds were found to be elevated when the masker frequency was within roughly 1 octave of the test frequency. On the other hand, postadaptation thresholds were not elevated when the test frequency was close to the adapting frequency but were elevated at about twice the adapting frequency. Thus masking and adaptation have quite different effects on spatial frequency discrimination, though their effects on contrast sensitivity are qualitatively similar. It is proposed that discrimination is determined by opponent-size processing. Adaptation elevates discrimination threshold by reducing the sensitivity of opponent elements. The masker grating elevates threshold by increasing the noise level of opponent elements, thus reducing the precision with which the visual pathway encodes spatial frequency. PMID- 4020513 TI - Uncertainty relation for resolution in space, spatial frequency, and orientation optimized by two-dimensional visual cortical filters. AB - Two-dimensional spatial linear filters are constrained by general uncertainty relations that limit their attainable information resolution for orientation, spatial frequency, and two-dimensional (2D) spatial position. The theoretical lower limit for the joint entropy, or uncertainty, of these variables is achieved by an optimal 2D filter family whose spatial weighting functions are generated by exponentiated bivariate second-order polynomials with complex coefficients, the elliptic generalization of the one-dimensional elementary functions proposed in Gabor's famous theory of communication [J. Inst. Electr. Eng. 93, 429 (1946)]. The set includes filters with various orientation bandwidths, spatial-frequency bandwidths, and spatial dimensions, favoring the extraction of various kinds of information from an image. Each such filter occupies an irreducible quantal volume (corresponding to an independent datum) in a four-dimensional information hyperspace whose axes are interpretable as 2D visual space, orientation, and spatial frequency, and thus such a filter set could subserve an optimally efficient sampling of these variables. Evidence is presented that the 2D receptive-field profiles of simple cells in mammalian visual cortex are well described by members of this optimal 2D filter family, and thus such visual neurons could be said to optimize the general uncertainty relations for joint 2D spatial-2D-spectral information resolution. The variety of their receptive-field dimensions and orientation and spatial-frequency bandwidths, and the correlations among these, reveal several underlying constraints, particularly in width/length aspect ratio and principal axis organization, suggesting a polar division of labor in occupying the quantal volumes of information hyperspace.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4020514 TI - Hyperacuity thresholds of 1 sec: theoretical predictions and empirical validation. AB - Bisection thresholds were measured as a function of the separation of the lines. For separations of less than 1.5 min, the addition of flanking lines facilitates bisection so that thresholds of less than 1 sec for discriminating the direction of offset could be reliably obtained. For larger separations an interval could be bisected to an accuracy of 1 part in 60. Experiments varying the length, luminance, and overlap of the lines suggest that different cues are used in these two regimes. A dual space-size analysis is presented that can account for these bisection thresholds over a wide range of experimental conditions. This quantitative analysis produces viewprints of the stimuli (analogous to the voiceprint of audition). Each viewprint shows the output of many spatial filters of different positions and sizes. A new filter shape is introduced that has advantages for modeling the visual system. The sensitivity of each filter is fixed by the contrast-response function. The analysis further shows that the limiting factors in spatial hyperacuity are both the contrast-response function and the spatial grain. PMID- 4020515 TI - Discrimination of contour curvature: data and theory. AB - Visual discrimination of contour curvature was investigated using stimuli having a single point of maximum curvature and a continuous derivative. Curvature discrimination as a function of mean curvature could be described by a power law with an exponent averaging 1.57. Data were also gathered as a function of line width, stimulus orientation, and retinal eccentricity. Finally, masking experiments provided evidence that the mechanisms responsible for curvature discrimination were both orientation and spatial-frequency selective. The data are well fitted by theoretical results derived from a line-element model that has recently been applied to spatial-frequency discrimination. PMID- 4020516 TI - Image segmentation at contour intersections in human focal vision. AB - It would be efficient for the visual image to be broken initially into small segments, each of which could be analyzed separately before being related to the others to build a representation of the whole. The places in the image where such segmentation should occur will depend on the image and will not be fixed points in retinal space. In this study, it is shown that high-precision-shape information cannot be integrated across contour intersections. It is suggested that contour intersections are a particular feature of the retinal image at which segmentation inevitably occurs. PMID- 4020517 TI - Spatial and spatial-frequency primitives in spatial-interval discrimination. AB - Thresholds for spatial-interval discrimination were determined under conditions designed to introduce randomness in the spatial-frequency content of the stimuli from trial to trial. Neither a random scaling of the display nor the addition of flanking bars at varying distances affected the observer's ability to judge the relative interval between pairs of bars, provided that the flanking bars were clearly resolved from the targets. Performance deteriorated only if the flanking bars were too close (less than about 2 arc min) or if the display was optically blurred. We conclude that the results pose difficulties for spatial-frequency theories of interval discrimination. PMID- 4020518 TI - Depth-increment detection function for individual spatial channels. AB - We have used stimuli with difference-of-Gaussian (DOG) luminance profiles to measure depth-increment thresholds within postulated spatial channels as functions of depth from the fixation plane. Stereoacuity was best with high frequency DOG's presented at the fixation plane. Performance was relatively constant for spatial frequency above 2.4 cycles/deg, but it deteriorated as spatial frequency was decreased. Regardless of spatial frequency, stereo sensitivity declined rapidly as stimuli were presented away from the horopter. The falloff occurred more rapidly over the 0-20-arc-min range than over the 20-80 arc-min range. Depth was perceived over a broader range of disparity pedestals with low-spatial-frequency stimuli; however, the lowest thresholds were always obtained with the highest-frequency stimuli. Both the falloff of sensitivity with disparity pedestal and the disparity range of quantitative stereo depth lead to the conclusion that different size-tuned channels process disparity differently. PMID- 4020519 TI - Distance perception with holographically reconstructed objects. AB - It has been assumed that a holographically reconstructed object is seen as though it is the actual object, including that it is seen at the distance of the actual object when it was holographed. A psychophysical experiment was carried out with seven subjects to test this assumption. The results clearly show that the perceived distances of holographically reconstructed objects are not equivalent to the perceived distances of actual objects. Thus a fundamental assumption in holography has not been supported by experimental data. PMID- 4020520 TI - Visual grating induction. AB - If a homogeneous illuminated test field is inserted within a sine-wave grating, an opposite phase grating will be perceived in the test field under a wide range of conditions. A cancellation technique was used to measure the magnitude of grating induction. The manner in which the effect depends on eye movements, inducing frequency, test-field height, inducing-field height, inducing amplitude, test-field luminance, and test-field width was determined in four experiments. Mathematical equations that describe these results are presented. It is shown that linear filters whose spatial weighting functions resemble receptive fields of the most common types of visual cell do not produce outputs with the properties of induced gratings. However, linear filters with highly elongated negative end zones and a small positive center produce opposite phase gratings in the test field, and an array of such filters of different sizes can account for several properties of induced gratings. There are other properties of the effect that are highly nonlinear. A second model, which is nonlinear and based on the properties of hypercomplex cells, is suggested that may encompass both the linear and the nonlinear properties of the effect. PMID- 4020521 TI - Recent trends in pregnancy among teenagers in Oklahoma. PMID- 4020522 TI - Limiting antibiotics on the hospital formulary. PMID- 4020523 TI - Estimated physician manpower requirements for Oklahoma in 1990. PMID- 4020524 TI - Physician manpower production critique. State of Oklahoma. Council on Medical Education of the Oklahoma State Medical Association. PMID- 4020525 TI - Young drug abusers' problems of attachment to the family. Some consequences for treatment. PMID- 4020526 TI - Conjoint treatment of spouses: clinical experiences. PMID- 4020527 TI - Drosophila mushroom body mutants are deficient in olfactory learning. AB - Two Drosophila mutants are described in which the connections between the input to and the output from the mushroom bodies is largely interrupted. In all forms of the flies (larva, imago, male, female) showing the structural defect, olfactory conditioning is impaired. Learning is completely abolished when electroshock is used as reinforcement and partially suppressed in reward learning with sucrose. No influence of the mushroom body defect on the perception of the conditioning stimuli or on spontaneous olfactory behavior is observed. The defect seems not to impair learning of color discrimination tasks or operant learning involving visual cues. PMID- 4020528 TI - Proximal renal tubular acidosis in methylmalonic acidemia. AB - A patient with methylmalonic acidemia was found to have a persistent hyperchloremic acidosis. Investigation documented the presence of a proximal renal tubular acidosis. Between 14 and 18 months of age the urinary pH was as high as 8.0 when the serum bicarbonate was 17 mEq/liter and the threshold for bicarbonate was at 16-17 mEq/liter. When restudied at 33 months of age, the threshold had risen to 20 mEq/liter, but this was still abnormal and supplemental treatment was required to keep the serum concentration of bicarbonate above 20 mEq/liter. It is postulated that organic acid metabolites which accumulate in this and related disorders may interfere with renal tubular function as has been shown for maleic acid in experimental animals. PMID- 4020530 TI - A qualitative and quantitative light microscopic study of the inferior olivary complex in the adult staggerer mutant mouse. AB - In the homozygous staggerer (sg/sg) mutant mouse, most of the Purkinje cells (the primary targets for olivocerebellar climbing fibers) are missing or ectopic. In this study, the organization and cell number of the inferior olivary complex in sg/sg were determined and compared to the inferior olive of the wildtype (+/+) mouse. Our results indicate that there is a marked disorganization and loss of almost 60% of the cells within the inferior olivary complex. This suggests that the inferior olive may be secondarily affected by the staggerer gene due to the defects in its main target cell, the Purkinje cell. PMID- 4020529 TI - Alanine decreases the protein requirements of infants with inborn errors of amino acid metabolism. AB - Supplementation with alanine was found to increase growth in weight and nitrogen balance in 5 infants with a variety of inborn errors of amino acid metabolism receiving diets restricted in protein. The addition of alanine to the regimen led to a mean increase in weight of 15 g/day. This and the increased nitrogen balance of 15 mg/kg/day were highly significant statistically. In addition a dose response effect of alanine was observed. The effect of alanine was compared with that of a supplemental mixture of essential and non-essential amino acids, lacking only those considered to be toxic in these patients. Alanine at 0.05 g/kg was as effective in promoting growth in weight as 1.05 g/kg of the amino acid mixture, while 0.25 g/kg of alanine was more effective than 0.70 g/kg of the amino acid mixture. The protein sparing anabolic effect of alanine is thought to be a reflection of the alanine glucose cycle. PMID- 4020531 TI - Properties of succinic semialdehyde dehydrogenase in cultured human lymphoblasts. AB - A direct assay has been developed for succinic semialdehyde dehydrogenase in sonicates of human lymphocytes and Epstein-Barr Virus transformed cultured lymphoblasts. Enzyme activity was quantified by incubating cell extracts with uniformly labeled [14C]succinic semialdehyde and monitoring the conversion to [14C]succinic acid. Radiolabeled products were separated by liquid partition chromatography on hydrated silicic acid. Kinetic properties and requirements of succinic semialdehyde dehydrogenase in lymphoblast sonicates were investigated in order to determine optimal conditions for the direct assay. Enzyme activity was stimulated by dithiothreitol, ammonium and potassium ions and 0.1% Triton X-100. The concentrations for half maximal activation by ammonium and potassium were 5.2 and 13.7 mM respectively. The mean activity of succinic semialdehyde dehydrogenase in assays in which equimolar NADP+ had been substituted for NAD+ was 19% of the activity of assays which contained NAD+. Substrate Michaelis constants were 21 and 30 microM for NAD+, and 26, 42 and 70 microM for succinic semialdehyde. The enzyme displayed a pH optimum between 8 and 9 and demonstrated a slight temperature activation between 37 degrees and 45 degrees C. A deficiency of succinic semialdehyde dehydrogenase activity was documented in cultured lymphoblasts derived from a patient with gamma-hydroxybutyric aciduria. PMID- 4020533 TI - Role of DNA in brain activity. Molecular engineering on the brain. International symposium. Ravello, Italy, May 27-29, 1985. Abstracts. PMID- 4020532 TI - Duplication 12q24----qter in an infant with Dandy-Walker syndrome. AB - A boy with the Dandy-Walker syndrome associated with multiple congenital abnormalities is described. Chromosomal analyses revealed an abnormal chromosome 21, inherited from his father who had a balanced translocation involving chromosomes 12 and 21: rcp(12;21)(q24.1;q22.1). The clinical features of this patient are compared with published descriptions for duplication 12q24----qter and a review of the literature pertaining to chromosomal anomalies found in other patients with the Dandy-Walker syndrome is presented. PMID- 4020534 TI - New acetylcholinesterase-deficient mutants of the nematode Caenorhabditis elegans. AB - We have used visual screening for a mutationally induced uncoordinated phenotype, coupled with subsequent enzymatic assay, to isolate 19 new mutations producing acetylcholinesterase (AChE) deficiencies in the nematode Caenorhabditis elegans. At least 13 of these are independent, and all fall within two genes, ace-1 X and ace-2 I, previously shown to control respectively two kinetically distinct major AChE classes, A and B. Three of the 4 new ace-1 alleles and one of the 15 new ace 2 alleles are apparently leaky; the rest are probably null. For the 3 leaky ace-1 alleles, qualitative changes in the residual class A AChE strongly support the contention that ace-1 is a structural gene. In ace-2;ace-1 mutants, marked reduction in class A and B AChE reveals a third, minor, previously unrecognized AChE class, designated C. PMID- 4020535 TI - A novel class of acetylcholinesterase, revealed by mutations, in the nematode Caenorhabditis elegans. AB - In ace-2;ace-1 double mutants of the nematode C. elegans, where the major acetylcholinesterase (AChE) classes A and B have been eliminated by mutation, the animals are viable and residual AChE activity remains. This residual activity differs markedly from AChE classes A and B; its Km for acetylcholine is 1000-5000 fold lower, its resistance to eserine is 3000-260,000-fold higher, it is markedly more thermolabile, and it can be separated from classes A and B by ion exchange chromatography. It has been designated class C AChE. Class C AChE of indistinguishable properties is also present in wild type C. elegans, at levels approximating those seen in ace-2;ace-1 double mutants, suggesting that it is controlled by a third, as yet unidentified, gene. Amongst other sources examined, class C-like AChE has been detected in another nematode species, Stephanurus dentatus, but not in Drosophila melanogaster, Torpedo californica, or Rattus rattus. PMID- 4020536 TI - Beer brewing as an ethnological catalyst. PMID- 4020537 TI - A reevaluation of psychotomimetic amphetamine derivatives in humans. PMID- 4020538 TI - The disease controversy: of metaphors, maps and menus. PMID- 4020539 TI - Antimicrobial therapy in infants and children: update 1976-1985. Part I. PMID- 4020540 TI - Caustic substance injuries. AB - Caustic and corrosive substance ingestions are a significant cause of early and late morbidity and may cause esophageal carcinoma after a long latent period. Initial management should be directed at the assurance of adequate ventilation and cardiovascular stability as well as the prevention of vomiting. Early esophagoscopy (to the level of first lesion, if present) is useful to identify those patients who do not need hospitalization or treatment. Esophagoscopy and contrast esophagram are useful to define the full extent of esophageal injury, but should be withheld until after the acute phase. Glucocorticoids are probably useful in limiting the extent and severity of esophageal stricture, the most frequent and significant long-term sequela. Colon interposition is used in those situations in which dilation of a stricture has been unsuccessful, and may prevent the subsequent development of esophageal carcinoma. PMID- 4020541 TI - Acute splenic sequestration in homozygous sickle cell disease: natural history and management. AB - Of a cohort of 308 children with homozygous sickle cell disease diagnosed at birth, 89 experienced 132 clinically significant attacks of acute splenic sequestration (ASS) over a 10-year period. The age at first attack ranged from 3 months to 6 years. Survival curve analysis of the interval until first attack indicated a cumulative probability of 0.225 by 2 years, and 0.265 by 3 years, and 0.297 by 5 years of age. Thirteen events were fatal, 11 during the first attack, and all before transfusion could be instituted. Recurrences occurred in 49% of survivors of the first attacks, and there were diminishing intervals between subsequent events. Respiratory symptoms were associated with 52 of 132 events, but bacterial isolates on blood culture were less frequent, and ASS was not prevented by pneumococcal vaccine or penicillin prophylaxis. A high fetal hemoglobin level protected against attacks of ASS. A parental education program aimed at early diagnosis of ASS was followed by an increase in the incidence rate for ASS from a mean of 4.6 per 100 patient-years to 11.3 per 100 patient-years, probably reflecting increased awareness of the complication. During the same periods, the fatality rate fell from 29.4 per 100 events to 3.1 per 100 events. The improvement in outcome is likely to have resulted from improvement in medical management and earlier detection of ASS. PMID- 4020543 TI - Herpes simplex virus encephalitis during childhood: importance of brain biopsy diagnosis. AB - Twelve consecutive pediatric patients 1 day to 11 years of age with suspected herpes simplex virus (HSV) encephalitis underwent brain biopsy. Five were proved to have HSV encephalitis; seven had subdural empyema, malignant glioma, enteroviral encephalitis, (one each), and presumed viral encephalitis, non-HSV (four). Neither epidemiologic, clinical, nor noninvasive laboratory tests were able to help differentiate the two groups of patients. The EEG was more sensitive than the CT scan in demonstrating focal lesions in early HSV encephalitis. In patients with HSV encephalitis, the mean time from hospital admission to appropriate antiviral chemotherapy was 3 days, and the outcome of HSV encephalitis was uniformly poor. In patients with febrile encephalitis-like syndromes with CSF pleocytosis, focal neurologic signs, or other localizing test results (EEG, CT), anticipatory antiviral chemotherapy and brain biopsy are the only hope to prevent the poor outcome associated with HSV encephalitis, to exclude other treatable conditions, and to avoid multiple types of unnecessary empiric therapies. PMID- 4020542 TI - Pacemaker management for acute onset of heart block in childhood. AB - Four children aged 2 to 15 years are described who had Stokes-Adams syndrome as the primary cardiac manifestation of complete heart block. All had mild, nonspecific antecedent symptoms without signs of congestive heart failure. Viral neutralizing antibody titers (coxsackievirus B1 and B2) rose significantly in two patients. Electrocardiography demonstrated complete heart block associated with one or more of the following: right bundle branch block, left anterior hemiblock, left bundle branch block, intraventricular conduction delay, and ventricular standstill. In addition, second-degree heart block was seen during the initial or resolving phases of illness. To prevent further life-threatening episodes of Stokes-Adams syndrome, temporary transvenous pacemakers were placed. Two patients with persisting complete heart block required permanent pacemakers. At last examination, the remaining two patients had sinus rhythm and normal conduction. Nonsurgical acquired complete heart block is unusual in childhood, and may be the only manifestation of myocarditis. Extreme bradycardia, which causes syncope, requires immediate temporary cardiac pacing; if the bradycardia persists, a permanent pacemaker should be implanted. PMID- 4020544 TI - Proximal airway function 8 to 16 years after laryngomalacia: follow-up using flow volume loop studies. AB - Twenty children who had endoscopically confirmed laryngomalacia were reviewed at 8 to 16 years of age. All had developed stridor in the first 6 weeks of life; stridor had stopped or largely resolved by age 4 years. Proximal airway function was assessed by expiratory and inspiratory flow volume loops and compared with control values. These children as a group had variable extrathoracic obstruction to inspiratory airflow, as indicated by a significantly low maximal inspiratory flow at 50% of vital capacity and a high mean ratio of maximal expiratory to maximal inspiratory flow at 50% vital capacity. Although limitation to inspiratory airflow was detectable in later childhood, it was not associated with troublesome symptoms. Significant stridor always resolved by 4 years of age, but some children experienced minor stridor under stress in later childhood. PMID- 4020545 TI - Environmental deprivation and transient elevation of sweat electrolytes. AB - We report five children who had transient elevations in sweat electrolyte values in association with environmental deprivation. The high electrolyte values were not always associated with malnutrition, and normalized more rapidly than weight. The reason for these abnormalities is unknown. In as much as elevated sweat electrolytes are rarely associated with environmental deprivation, repeat studies are recommended before diagnosing cystic fibrosis in such children. PMID- 4020546 TI - Hypercalciuria in children with juvenile rheumatoid arthritis: association with hematuria. AB - After discovering juvenile rheumatoid arthritis (JRA), hematuria, and urolithiasis associated with hypercalciuria in two children, urinary calcium excretion was examined in 38 patients with JRA. Fasting urine calcium/creatinine (mg/mg) (UCa/UCr) ratios were increased (greater than 0.21) in 12 patients, who had a mean UCa/UCr ratio of 0.34 +/- 0.14, compared with 0.09 +/- 0.06 in 26 normocalciuric patients with JRA. Increased UCa/UCr ratios were found more frequently in patients with systemic JRA (P less than 0.05); however, no relationship between UCa/UCr ratios and either functional classification or drug therapy was observed. Four children with increased urine calcium to creatinine ratios were examined more extensively. Twenty-four-hour urine calcium excretion ranged from 4.0 to 7.2 mg/kg/24 hours. An orally administered calcium loading test demonstrated fasting hypercalciuria after dietary calcium restriction in these four patients. Serum calcium, bicarbonate, phosphorus, and parathyroid hormone values were normal. Hematuria was found in six of 12 hypercalciuric patients with JRA but in only three of 26 normocalciuric patients (P less than 0.016). We conclude that urinary calcium excretion is frequently increased in patients with JRA and that hypercalciuria may be related to the pathogenesis of hematuria in some of them. PMID- 4020547 TI - Anorexia nervosa by proxy. PMID- 4020548 TI - What represents pleocytosis in blood-contaminated ("traumatic tap") cerebrospinal fluid in children? PMID- 4020549 TI - String test in evaluation of cholestatic jaundice in infancy. PMID- 4020550 TI - Serum bile acid levels in patients with extrahepatic biliary atresia and neonatal hepatitis during the first 10 days of life. PMID- 4020551 TI - Newborn screening for maple syrup urine disease. PMID- 4020552 TI - Urinary citrate excretion in children with hypercalciuria. PMID- 4020553 TI - Pseudotumor cerebri associated with cerebral venous sinus thrombosis, internal jugular vein thrombosis, and systemic lupus erythematosus. PMID- 4020554 TI - Occurrence of neuroblastoma and asymmetric crying facies: case report and review of the literature. PMID- 4020555 TI - Association of multinodular goiter, cystic renal disease, and digital anomalies. PMID- 4020556 TI - Umbilical cord length: clinical significance. AB - Umbilical cord length in 35,779 neonates was analyzed to determine values after mid-gestation and to see if abnormal values have clinical significance. Growth slowed after twenty-eighth week of gestation but did not stop before term. Cord length had a positive correlation with maternal height, pregravid weight, pregnancy weight gain, socioeconomic status, and the fetus being male. Short cords were associated with subsequent psychomotor abnormalities, but taken alone their predictive value was low because the normal range of cord lengths is large. Short cords were much better predictors of subsequent impairments when they were combined with other neonatal predictors. Short cords doubled or tripled the predictive values of low Apgar scores and several other neonatal abnormalities for subsequent low IQ values and neurologic abnormalities. PMID- 4020557 TI - Systemic to pulmonary collaterals mimicking patent ductus arteriosus in neonates with prolonged ventilatory courses. PMID- 4020558 TI - When is umbilical cord separation delayed? PMID- 4020559 TI - Pharmacokinetics and pharmacodynamics of cimetidine and metabolites in critically ill children. AB - Cimetidine and antacids are the mainstays of therapy for the prophylaxis of stress-induced ulceration in critically ill children. Previous cimetidine dosing recommendations have been empiric because of a lack of knowledge about cimetidine disposition kinetics in children. Thirty children, mean age 9 +/- 3.2 years, were admitted to the study with the following primary diagnoses: closed head injury (23 patients), sepsis (four), gunshot wound (two), and bleeding gastric ulceration (one). The mean dose of cimetidine was 26 mg/kg/day, administered intravenously over 15 minutes in four divided doses. Cimetidine disposition was best described by a biphasic elimination curve with t1/2 values for cimetidine, cimetidine sulfoxide, and hydroxymethyl cimetidine of 1.39, 2.6, and 4.7 hours, respectively. Cimetidine plasma concentrations were maintained at greater than or equal to 0.5 microgram/ml for a significantly longer time in patients who received greater than or equal to 20 mg/kg/day. Most patients had a plasma cimetidine concentration below 0.5 to 1.0 microgram/ml 4 hours after infusion. The mean apparent volume of distribution and total body clearance for cimetidine were 1.23 L/kg and 10.4 ml/min/kg, respectively. A significant correlation was found between age and either apparent volume of distribution (r = 0.76, P less than 0.001) or total body clearance (r = 0.75, P less than 0.001). No significant correlation between cimetidine concentrations in either plasma or gastric juice and gastric pH could be determined. However, seven of nine patients who received only cimetidine had a gastric pH of greater than or equal to 4 at 2 hours after infusion when the plasma cimetidine concentration was greater than or equal to 1.0 or the gastric juice concentration was greater than or equal to 2.0 microgram/ml. The mean gastric pH was 2.2 at 6 hours, when plasma and gastric juice concentrations of cimetidine were greater than or equal to 1.0 microgram/ml. On the basis of our data, a cimetidine dosage of 20 to 30 mg/kg/day administered in six divided doses should provide for average steady-state plasma cimetidine concentrations of 1.3 to 2.0 micrograms/ml. PMID- 4020560 TI - Pharmacokinetic determination of ranitidine pharmacodynamics in pediatric ulcer disease. AB - The pharmacokinetics and pharmacodynamics of ranitidine were evaluated during three methods of administration in 12 children ranging in age from 3.5 to 16 years with documented gastric or duodenal ulcer disease. First, a continuous intravenous infusion of ranitidine was administered to determine the serum concentration necessary to suppress gastric acid secretion by at least 90%. From these data a therapeutic dose of ranitidine was calculated and administered on separate days via the intravenous bolus and oral routes. Half-life, volume of distribution, and clearance values for ranitidine were the same after intravenous bolus and oral doses (1.8 vs 2.0 hours, 2.3 vs 2.5 L/kg, and 794.7 vs 788.0 ml/min/1.73 m2, respectively). The bioavailability of ranitidine given orally averaged 48%. Serum ranitidine concentrations necessary to inhibit gastric acid secretion by at least 90% ranged between 40 and 60 ng/ml for all children studied. No adverse clinical or biochemical effects were observed in any child during the 6 weeks of orally administered treatment. Endoscopic reevaluation after 6 weeks indicated complete healing of initial ulcers. PMID- 4020561 TI - Percutaneous administration of theophylline in the preterm infant. AB - The preterm infant's skin is a poor barrier to the absorption of chemical agents. The possibility of turning this to the infant's advantage was explored by using the percutaneous route to administer theophylline. A standard dose of theophylline gel, equivalent to 17 mg anhydrous theophylline, was applied to an area of skin 2 cm in diameter over the upper abdomen under an occlusive dressing, and serial theophylline levels were measured; 25 studies were performed in 20 infants of less than or equal to 30 weeks gestation. Therapeutic theophylline levels (greater than 4 mg/L) were achieved in 11 of 13 infants who had not previously received the drug, and were maintained for up to 72 hours. In 12 studies in infants who were previously receiving aminophylline intravenously, theophylline levels were maintained for up to 70 hours. There was a significant decline in the amount of theophylline absorbed in the first 24 hours after application as the infant's postnatal age increased, but satisfactory blood levels were achieved in infants up to 20 days of age. The percutaneous route is a feasible method of administering theophylline in preterm infants. PMID- 4020562 TI - Transient defect in the synthesis of biopterin. PMID- 4020563 TI - Panic attack following injection of aqueous procaine penicillin G (Hoigne syndrome) PMID- 4020564 TI - Management of mild iron deficiency. PMID- 4020565 TI - Prematurity and premature thelarche. PMID- 4020566 TI - Effect of non-nutritive and nutritive suck on gastric emptying in premature infants. AB - Ten healthy preterm infants were studied to determine if non-nutritive and nutritive suck significantly altered gastric emptying patterns when compared with gavage feeding alone. We used a 10% dextrose meal with phenol red marker and a double sampling technique to determine gastric emptying at 10-min intervals over a 30-min test period. A crossover study design compared the effects of the three feeding methods in each infant. The gastric residual volumes expressed in milliliters per kilogram did not differ significantly when comparisons were made among groups at 10, 20, and 30 min following the test meal. Non-nutritive suck and nutritive suck and swallow of a liquid dextrose meal do not significantly improve gastric emptying in healthy preterm infants. The beneficial effects of non-nutritive and nutritive sucking on the nutritional status of preterm infants, demonstrated by others, are not related to improved gastric evacuation of feeds. Alternative explanations for these beneficial effects require further investigation. PMID- 4020567 TI - Continuous gastric pH measurement in young and older healthy preterm infants receiving formula and clear liquid feedings. AB - Gastric pH was recorded with an intragastric pH electrode for 12 h in two groups of healthy, preterm infants with similar birth weights (range 1.4 to 2.0 kg). Group I infants (n = 13) were less than 7 days old and Group II infants (n = 10) were 7-15 days old. Infants were fed three formula feedings and one clear liquid feeding during the study. In Group I, mean gastric pH measured at 15-min intervals was above 4.0 for 3 h after either feeding. In Group II mean gastric pH was lower particularly after clear liquid feedings, where it remained below pH 4.0 for the entire 3-h postprandial period. The percent of monitored time at gastric pH less than 4.0 was low in Group I--15.2 +/- 4.2% and 20.6 +/- 6.4% after formula and clear liquid, respectively. The percent time was greater in Group II--42.7 +/- 8.0% and 61.9 +/- 7.3% after formula and clear liquid, respectively. In the younger preterm infant, gastric pH does not appear sufficiently low to support peptic activity. PMID- 4020568 TI - Seventeen-hour continuous esophageal pH monitoring in the newborn: evaluation of the influence of position in asymptomatic and symptomatic babies. AB - Esophageal pH monitoring has been performed in 60 asymptomatic neonates between 1 and 10 days old. Several parameters (periods with a pH less than 4, number of reflux episodes, number of reflux episodes lasting more than 5 min, average duration of the longest reflux episode, average pH) were studied in different positions (in prone and supine position, in right and left side lying position). For all parameters, except for the average pH, we obtained significantly more favorable results in prone position. In 22 vomiting neonates, significantly favorable results were obtained only by application of positional therapy: in prone position with head elevated (anti-Trendelenburg). There was no significant difference between the symptomatic group (with radiologically proven reflux pathology) in prone and anti-Trendelenburg position, and the control group in prone horizontal position. The 17-h continuous pH monitoring in the newborn is a nonaggressive investigation technique in physiological circumstances, which adequately completes and/or replaces the traditional examinations on gastroesophageal reflux. This method enables an evaluation of the favorable effect of simple therapeutic means (positional changes). Medication, and thickening and staggering of feeding (a time-consuming and tiring burden for the parents), can be avoided with this technique. PMID- 4020569 TI - Oral rehydration, rapid feeding, and cholestyramine for treatment of acute diarrhea. AB - Different combinations of fluid therapy, feeding regimen, and cholestyramine were compared in search for optimal treatment of infants hospitalized for acute diarrhea. The infants (n = 81) received either rapid oral rehydration using the oral rehydration solution-World Health Organization formula (sodium 90 mmol/L, ORS-WHO) or traditional oral fluid replacement using a commercial glucose electrolyte solution (sodium 35 mmol/L). One-half of the infants in both groups received full feedings at 24 h of hospitalization; in the remaining infants, feedings were gradually introduced over a period of 5 days. In addition, all the children were randomized to receive either cholestyramine 2 g four times daily or an equivalent amount of placebo. Rehydration with ORS-WHO, but not traditional fluid replacement therapy, led to correction of initial metabolic acidosis after 6-10 h; no cases of hypernatremia were observed with the use of ORS-WHO. Rapid return to full feedings appropriate for age, including milk products, was associated with better weight gain and significantly shorter duration of diarrhea compared with gradual introduction of feedings. Cholestyramine treatment further shortened the duration of diarrhea without adverse effects in those children who had received ORS-WHO and thus were properly rehydrated. In contrast, in children with poor initial hydration, cholestyramine treatment was associated with prolonged metabolic acidosis. We conclude that treatment of acute diarrhea by rehydration with ORS-WHO and rapid introduction of full feedings is effective and safe, and this combination forms a therapy of choice for typical hospitalized cases of acute infantile diarrhea in Finland. Cholestyramine may be of value as an adjunct therapy after adequate rehydration. PMID- 4020570 TI - Autoimmunity in diarrhoeal disease. AB - Evidence for autoimmunity in diarrhoeal disease is reviewed. Firstly, coeliac disease (CD) is considered. The incidence of tissue-reactive autoantibodies in both adults and children with CD (68% and 65%, respectively) is higher than the incidence of these autoantibodies in controls (6% in normal adults, and 14% and 9% in disease controls drawn respectively from adult and child populations). The R1 antireticulin antibody, when present, was found to disappear after several weeks on a gluten-free diet, but in contrast, other autoantibodies persisted. Secondly, a case is argued for a new disease category, namely "autoimmune enteropathy." Seven cases are reviewed in which patients presented with protracted diarrhoea, a small intestinal enteropathy which failed to heal during periods of total parenteral nutrition, and evidence of a predisposition to autoimmunity (namely, the presence of high titre autoantibodies including one specific for gut epithelium, and/or the presence of associated diseases regarded to be autoimmune). Thirdly, evidence for autoimmunity in inflammatory bowel disease is reviewed and includes discussion of serum goblet cell antibodies and of circulating T cells which participate in antibody-dependent cellular cytotoxicity in vitro using colonic epithelial cells as targets. Finally, an unusual child is described who presented with chronic diarrhoea and a flat small intestinal mucosa, who responded to gluten withdrawal but who later relapsed spontaneously during a strict gluten-free diet. Her mucosa healed only after a period of total parenteral nutrition and treatment with oral steroids. This child's enteropathy was also associated with thyrotoxicosis and a microscopic colitis. PMID- 4020571 TI - Value of breath hydrogen analysis in management of diarrheal illness in childhood: comparison with duodenal biopsy. AB - Breath hydrogen tests were carried out on 157 children either because they had chronic diarrhea or because they were on disaccharide-free diets. Lactose malabsorption was common in patients with postgastroenteritis syndrome (43%), and sucrose malabsorption was readily detected in patients with congenital sucrase isomaltase deficiency. Secondary sucrose malabsorption and small bowel bacterial overgrowth were also detected. In predicting clinical response to dietary change, the breath hydrogen test, as we perform it, was clearly the most specific and sensitive and had a predictive accuracy of 96%. Duodenal biopsy results obtained from 48 of the children gave a 23% incidence of misleading disaccharidase results (16.7% falsely normal, 6.3% falsely abnormal), but biopsy remains vital in the diagnosis of congenital sucrase-isomaltase deficiency. False negative breath hydrogen results were obtained on occasions (4%) but in most instances were related to recent antimicrobial therapy or failure of the breath test mechanics (e.g., vomiting, length of sampling). PMID- 4020572 TI - Habit training as treatment of encopresis secondary to chronic constipation. AB - Fifty-eight encopretic children were placed on a habit training regimen consisting of initial disimpaction followed by attempts to defecate after a specific meal, and use of enemas contingent on failure to defecate for 2 successive days. All patients had gross incontinence of long duration. After an average of less than four visits in 5 months, 83% had an excellent outcome, 60% were completely continent, and 23% had only staining. Patients not achieving continence averaged a 90% decrease in frequency of incontinence. The mean frequency of incontinent episodes decreased from 13.2 to 0.52 per week, while appropriate bowel movements increased from 3.8 to 5.9 per week. At follow-up (average of 3 years), 61% of 43 patients contacted had excellent outcomes, 51% were continent, and 10% had only staining. Patients still incontinent at follow up averaged 89% fewer episodes than they had prior to treatment. These findings show habit training to be a rapidly effective and long-lasting treatment for encopresis secondary to chronic constipation. PMID- 4020573 TI - Iron and the exclusively breast-fed infant from birth to six months. AB - This study was designed to determine whether normal, full-term, exclusively breast-fed infants develop iron deficiency anemia, as defined by hemoglobin or red blood cell indices more than two standard deviations below the age-specific mean, or depletion of iron stores, as defined by an abnormally low serum ferritin level. Thirty-three breast-fed infants were followed from birth to 6 months. Maternal blood and cord blood at delivery, and venous blood from the infants at 2, 4, and 6 months were analyzed for anemia as defined above. At 6 months of age, the mean hemoglobin concentration of these infants was slightly higher than the normal mean; four of 33 infants (12%) had a mean corpuscular volume greater than 2 SD below the reported normal mean; and two of 33 infants (6%) had a serum ferritin level less than 12 ng protein/ml. These data suggest that the infant who is exclusively breast-fed for the first 6 months of life is not at high risk for the development of iron deficiency anemia or the depletion of iron stores during that time. PMID- 4020574 TI - Breast-feeding among teenage mothers: milk composition, infant growth, and maternal dietary intake. AB - Information on breast-feeding was obtained from 25 mothers recruited from four high school programs for teenaged parents. Subjects were visited monthly 1-9 times (mean 3.7 visits) during the first 10 months of lactation to measure infant growth and maternal dietary intake and to collect a breast milk sample. Of 24 mothers visited more than once, 21 (88%) breast-fed for more than 3 months, and at least nine continued beyond 6 months. Compared to the nutrient content of milk samples from adult women, milk of teenage mothers was significantly lower in lactose, magnesium, calcium, potassium, and sodium. However, the differences in magnesium, calcium, and potassium may have been due to differences in the timing of sample collection. On the basis of infant growth, milk volume was judged to be adequate for 88% of the infants. Mean maternal energy and protein intakes were 2,897 kcal and 115 g, respectively; mean intakes of calcium, potassium, vitamin A, riboflavin, niacin, and vitamin C exceeded the National Research Council's Recommended Dietary Allowances (RDA) for lactation, while iron and thiamine intakes averaged 84% and 94% of the RDA, respectively. It is concluded that with active counseling teenage mothers are capable of successful lactation. PMID- 4020575 TI - Free fatty acids in the development of breast milk jaundice. AB - The incubation of milk, at 4 degrees C, from mothers of infants with breast milk jaundice (BMJ) is reported to result in significantly higher levels of free fatty acids (FFA) compared with milk from controls. Single milk samples collected under standard conditions were obtained from four mothers of infants with BMJ and 14 control donors matched for stage of lactation. Milk samples were analyzed for the concentrations of FFA, using thin-layer gas chromatographic techniques. In addition, serum total fatty acids were measured in mothers and infants. The concentrations of FFA increased after storage of the milk from both the jaundiced and control groups. No differences were observed in the composition of milk FFA before or after incubation, when respective values were compared between these two groups. Similarly, no differences were detected in serum total fatty acids in either infants or mothers. The observation that increased levels of FFA in milk are associated with BMJ was not confirmed. PMID- 4020576 TI - On the source of bile salt-stimulated lipase in human milk: a study based on serum concentrations as determined by sandwich enzyme-linked immunosorbent assay technique. AB - Human milk contains a bile salt-stimulated lipase (BSSL) which is considered to contribute significantly to lipid digestion in newborns. Human pancreatic juice contains an enzyme, carboxyl ester hydrolase (CEH), that is immunochemically and functionally identical to the milk enzyme. It has not been clear, however, whether the milk enzyme is synthesized within the mammary gland or whether the pancreatic enzyme is transported to the mammary gland for secretion. In this study we describe an enzyme-linked immunosorbent assay (ELISA) for determinations of BSSL and CEH in serum. Serum samples from healthy adults of both sexes contain significant amounts of enzyme (3.2 +/- 1.7 micrograms/L). Lactating women did not have higher serum levels, which would be expected if the milk enzyme were a product of the pancreas, and it was calculated that the concentrations found could not sufficiently account for the amounts secreted in the milk. We therefore conclude that BSSL is synthesized within the mammary gland. This conclusion is further strengthened by our findings that serum of breast-fed newborns contains very little if any enzyme. Since macromolecular absorption is high early in life, and witch's milk contains high enzyme levels, again one would expect high serum levels if BSSL were a pancreatic product. PMID- 4020577 TI - Hydrophobic interactions of human milk lipase. AB - The hydrolysis of a series of n-alkyl esters of 4-nitrobenzoic acid, and of isopropyl 4-nitrobenzoate, 4'-nitrophenyl 4-nitrobenzoate, and 4-nitrobenzoyl 1 monoglycerol, catalyzed by human milk lipase in the absence and presence of cholate stimulation, has been measured at pH 7.3, 37.5 degrees C. It has been shown that the enzyme possesses a specific alkyl binding site which is hydrophobic in nature and wide enough to accommodate two fatty acid chains lying side by side or a phenyl ring lying flat. The hydrophobic nature of this site is affected by bile salt stimulation of the enzyme. Hydrophobicity parameters have been calculated for hydrocarbon chains lying in the acyl and alkyl binding sites of human milk lipase. A mechanism is suggested for the role of bile salts in stimulating the enzyme in its activity against water soluble esters and water soluble triacylglycerols. PMID- 4020578 TI - Intralipid infusion in neonates: effects on polymorphonuclear leukocyte function. AB - In vivo and in vitro studies were done to assess the effects of Intralipid (IL) on neonatal polymorphonuclear leukocyte (PMNL) function. No significant abnormalities of chemotactic (CT) or chemiluminescent (CL) activities were noted in cord or adult PMNLs incubated with IL (10 mg/ml) when compared with paired controls incubated with buffer. In 14 premature and term neonates, IL was infused at 1 g/kg/24 h. Postinfusion CL activity of PMNLs was not significantly different from preinfusion CL activity. Although previous animal and human studies have shown abnormalities of PMNL function using higher infusion rates, slow infusion of IL at 1 g/kg/24 h produced no detectable alteration in PMNL oxidative function. The safety of long-term therapy with higher doses of IL remains to be proven. PMID- 4020579 TI - Development of colonic fluid and electrolyte transport: influence of weaning pattern. AB - The purpose of this study was to investigate the normal postnatal development of electrolyte and water transport in the large intestines of rats aged 10-20 days, to focus on the events taking place around the time of weaning, and to study the influence of different feeding patterns at the time of weaning on the normal development of the transport mechanisms in the large intestine. The net absorption of sodium, potassium, and water was investigated by using in vivo luminal isotonic perfusion in rats aged 12-40 days. The activity of the active transport enzyme Na-KATPase in the colonic mucosa of rats aged 10-40 days was determined. We found a significant decrease in the net absorption of electrolytes and water that was greatest around the time of weaning. Since the NaKATPase activity was lower in 10-16-day-old rats than in 40-day-old rats, we suggest that the high sodium and water uptake in the colon of suckling rats is independent of the sodium pump. Changes in the feeding patterns around the time of weaning, such as prolonged suckling, were associated with a significantly higher net absorption of electrolytes and water than in rats that were normally weaned at 20 days of age. The Na-KATPase activity was not significantly influenced by the weaning pattern. PMID- 4020580 TI - Influence of diet on the development of gastrin- and somatostatin-like immunoreactivity in the stomach of rats. AB - The effects of changes in diet on antral gastrin-like immunoreactivities and antral and corporal somatostatin-like immunoreactivities were studied in three groups of young male rats. Group 1 rats were weaned physiologically, group 2 rats received only breast milk, and group 3 rats were fed milk until 20 days of age and then were switched abruptly to laboratory chow. In group 1, antral gastrin like immunoreactivity and somatostatin-like immunoreactivity increased gradually from 13 days of age to adults. In group 2, antral gastrin-like immunoreactivity did not increase, and antral and corporal somatostatin-like immunoreactivity increased until 20 and 25 days of age, respectively. In group 3, there were three to fivefold increases of antral gastrin-like immunoreactivity and somatostatin like immunoreactivity after changing to laboratory chow. Dietary changes had no effect on the concentration of corporal somatostatin-like immunoreactivity. These results suggest that the developmental patterns of gastric gastrin-like immunoreactivity and somatostatin-like immunoreactivity are closely related to diet; laboratory chow may play an important role in the development of these gut hormones. PMID- 4020581 TI - Development of gastric histidine decarboxylase in the rat: sensitivity to fasting and secretagogues. AB - Gastric mucosal histidine decarboxylase (HDase) was measured in fetal rats between days 16 and 21 of gestation, and in newborn rats up to weaning. HDase was not detected in fetal stomach. Its activity developed from day 1 after birth (29 +/- 2 pmol CO2/mg protein/h) and increased up to day 18 when it reached the fed adult level (894 +/- 174 pmol CO2/mg protein/h). Weaning increased HDase activity significantly (weaned versus unweaned rats: 1,664 +/- 150 and 1,036 +/- 170 pmol CO2/mg protein/h; p less than 0.005). Up to day 18, HDase activity was not altered by 16 h to 24 h of fasting. From that day on, HDase became sensitive to both pentagastrin and carbachol. These results indicate that complete functional maturation of histamine-producing cells is only reached at day 18, just before weaning. This developmental pattern may explain the differences observed between fetal and adult regulation of gastric acid secretion. PMID- 4020582 TI - Intestinal tapering and lengthening for short bowel syndrome. AB - Intestinal tapering and lengthening were performed in a child with short bowel syndrome to prevent the need for home parenteral nutrition. The intestinal lengthening was not successful, presumably because the vascular anatomy was not favorable. Significant clinical improvement and avoidance of home parenteral nutrition resulted from the tapering procedure. These procedures have a role in the treatment of selected patients with short bowel syndrome. PMID- 4020583 TI - Multifocal osteonecrosis in adolescents with Crohn's disease: a complication of therapy? AB - Three adolescents with severe Crohn's ileocolitis developed osteonecrosis after receiving intravenous corticosteroids and parenteral nutrition, including 10% lipid infusion. Each had achieved clinical remission with therapy. However, several months following completion of therapy, each developed arthralgias and arthritis of weight-bearing and non-weight-bearing joints. Roentgenographic evaluation revealed osteonecrosis involving multiple joints. Osteonecrosis may result from the interference with blood flow to bone and has been produced in animals by infusion of lipid solutions and administration of corticosteroids. We report these cases of osteonecrosis as a probable complication of corticosteroid and lipid infusion in adolescents treated for severe Crohn's disease. PMID- 4020584 TI - Does breast feeding protect against development of clinical symptoms of celiac disease in children? PMID- 4020585 TI - Drug education: why we have so little impact. PMID- 4020586 TI - Factors associated with public health nurses' perceptions of skill in chemical dependency assessment and referral. PMID- 4020587 TI - The persistence of experimentally induced cognitive change: a neglected dimension in the assessment of drug prevention programs. PMID- 4020588 TI - Student consumer health knowledge and behavior in the marketplace. PMID- 4020589 TI - Effects of type of examiner, sex, and year in school on self report of drug use by high school students. PMID- 4020590 TI - Evaluating an educational program for the prevention of impaired driving among grade 11 students. PMID- 4020591 TI - Improving anti-smoking education: profiling the ex-smoker. PMID- 4020592 TI - Addiction to Zenachlor--drug issues from A to Z. PMID- 4020593 TI - Mushroom use by college students. PMID- 4020594 TI - Teachers' perceptions related to smoking education between 1973 and 1982. PMID- 4020595 TI - Substance abuse and teacher stress. PMID- 4020596 TI - The effect of locus of control and perceptions of school environment on outcome in three school drug abuse prevention programs. PMID- 4020597 TI - Identifying chemical use problems in a community clinic. PMID- 4020598 TI - North Carolina Drug Education School Evaluation Instrument. PMID- 4020599 TI - Behavioral assessment: advancing methodology in pediatric psychology. PMID- 4020600 TI - The Personality Inventory for Children and hyperactivity: clinical utility and generalizability problems. PMID- 4020601 TI - Revision of the Parenting Stress Index. PMID- 4020602 TI - Use of the PPVT-R for intellectual screening with a preschool pediatric sample. PMID- 4020603 TI - Diagnostic uses of the Vineland Adaptive Behavior Scales. PMID- 4020605 TI - The influence of positive affect on the unusualness of word associations. AB - A pilot study and two experiments investigated the influence of positive affect, induced in three differing ways, on the uniqueness of word associations. Persons in the positive-affect conditions gave more unusual first-associates to neutral words, according to the Palermo & Jenkins (1964) norms, than did subjects in the control conditions. In Study 3, where word type (positive, neutral, negative) was a second factor along with affect, in a between-subjects design, associates to positive words were also more unusual and diverse than were those to other words. These results were related to those of studies suggesting that positive affect may facilitate creative problem solving and to other work suggesting an impact of positive feelings on cognitive organization. PMID- 4020604 TI - Causal attributions of married couples: when do they search for causes? What do they conclude when they do? AB - In this study, we examined when and whether married people engage in attributional activity or form causal attributions to explain their partners' behavior. We used an indirect probe to better approximate naturally occurring cognitive activity. We also examined the content of spouses' causal attributions, using both direct and indirect probes. Spouses were asked about frequent as well as infrequent relationship events, and about partner behaviors that had positive or negative impacts on the recipient. Husbands in unsatisfying relationships reported more attributional thoughts than did happily married husbands, whereas wives in the two groups did not differ. Behaviors having negative impacts elicited more attributional activity than did positive behaviors. Behavioral frequency and impact interacted in ways contrary to predictions. Finally, distressed couples were particularly likely to report distress-maintaining attributions and were particularly unlikely to report relationship-enhancing attributions, compared with their nondistressed counterparts. PMID- 4020606 TI - Cross-cultural examination of the semantic dimensions of body postures. AB - In two studies, we examined the cross-cultural validity of the dimensional structures with which postures are judged. In Study 1, 686 Japanese subjects rated 40 posture expressions on sixteen 5-point semantic differential scale items. Subjects inferred an encoder's attitude towards oneself (i.e., the decoding subject) in hypothetical dyadic situations. A principal-component factor analysis yielded evidence for three independent dimensions resembling those proposed by Schlosberg (1954), Osgood (1966), and Williams and Sundene (1965). These three factors were named self-fulfillment, interpersonal positiveness, and interpersonal consciousness. In Study 2, 336 Japanese students again rated the 40 posture expressions on the sixteen 5-point differential items, but an attempt was made to control for the status of the hypothetical encoder. The results of this study essentially replicated those of Study 1. One interesting finding was that although we found the same factors as those found in studies conducted in the West, the order of the factors in our studies was the reverse of the order found in these previous studies. The findings are discussed in terms of proposed cultural differences in the maintenance of human relations. PMID- 4020607 TI - Adler's psychology (of use) today: personal history of traumatic life events as a self-handicapping strategy. AB - We investigated the hypothesis that the reporting of a history of traumatic life events may serve as a strategy to control attributions about performance in an evaluative setting (i.e., self-handicapping). Following from Alfred Adler's early theorization in the psychology of use, as well as more recent theory and research on self-handicapping, we predicted that individuals would emphasize the adversity of events and experiences in their background when an uncertain evaluation was expected and when a traumatic background would serve as a suitable excuse for potential failure. Results generally supported the hypothesized self-protective reporting of traumatic life events. PMID- 4020608 TI - Jealousy: loss of relationship rewards, loss of self-esteem, depression, anxiety, and anger. AB - White's (1981) theory of romantic jealousy states that the loss (or anticipated loss) of a romantic partner to a rival causes two kinds of suffering: loss (or anticipated loss) of relationship rewards and loss (or anticipated loss) of self esteem. Elaborating this theory, we proposed that loss of relationship rewards causes depression, whereas loss of self-esteem causes anxiety and anger. General support was found for White's theory and the elaborations, but not for the hypothesis that the loss of self-esteem causes anxiety. Anxiety may be a product of both loss of self-esteem and loss of relationship rewards. PMID- 4020609 TI - Perceptions of stressful life events and depression: a test of attributional models. AB - A brief review of tests of the attributional model of depression suggests that there is only weak or inconsistent support for the predicted causal ascriptions by depressed persons for negative events. Moreover, in very few studies have researchers actually tested the causal predictions of the model. Finally, because many of the studies were conducted with normal college students, the generality of the model as applied to different populations needs to be investigated. We addressed three questions: (a) the validity of the hypothesized independent and direction relation between each of the dimensions of internality, stability, controllability, intentionality, and globality and depression; (b) the causal relation between attributions and depression in a 2-month prospective study; and (c) evaluation of the model on two disparate samples: normal college students and elderly depressed outpatients ascribing causes for their personally stressful events. Causal modeling statistical procedures were applied to both the question of concurrent relations and causal relations between cognitions and depression. The results suggest minimal support for the attributional model: The dimensions were not each independently and directly associated with depression in the manner predicted by Abramson, Seligman, and Teasdale (1978), and the model that best fit the data was generally congruent for both the normal and clinical samples. In terms of direction of causality, the data were more consistent in indicating that depression causes cognitions than in indicating the reverse. PMID- 4020610 TI - The effects of private self-consciousness and perspective taking on satisfaction in close relationships. AB - We extended the scope of recent studies in which self-awareness and perspective taking have been used as predictors of social competence or adjustment: We analyzed their influence on the satisfaction experienced in monogamous, heterosexual relationships. Members of 131 couples answered questions concerning themselves and their relationships. We predicted that individual differences in private self-consciousness would be positively related to relationship satisfaction because of the greater self-disclosure resulting from that heightened self-attention. Second, we predicted that individual differences in perspective taking would foster relationship satisfaction, independent of any influence of self-disclosure. Both expectations were confirmed. Scores on the private self-consciousness scale were predictive of reported self-disclosure, and self-disclosure was predictive of satisfaction in the relationship. Furthermore, once the influence of self-disclosure was removed, no effect of self consciousness on satisfaction remained. In contrast, after disclosure was controlled, perspective-taking scores were significantly related to satisfaction and were in fact unrelated to disclosure at all. These findings indicate that two personality characteristics having to do with habitual attention to behavioral tendencies, to emotions, and to motivations significantly enhance the quality of close heterosexual relationships in different ways. Results are discussed in terms of current theory in the related fields. PMID- 4020611 TI - Women's involvement in multiple roles and psychological distress. AB - Women's involvement in multiple roles was examined in relation to three stress indices: role overload, role conflict, and anxiety. Using hierarchical multiple regression analyses, effects of number of roles occupied; occupancy of the particular roles of paid worker, wife, and mother; and the quality of a woman's experience in her roles were analyzed. Data were from a disproportionate stratified random sample (N = 238) of Caucasian women between 35 and 55 years of age. For the total sample and for employed women, occupancy of the role of mother was related to two stress indices; occupancy of the role of paid worker was related to none. The quality of experience in the work and parental roles was a significant predictor of role overload; quality of parental role experience was a significant predictor of role conflict and of anxiety. PMID- 4020612 TI - The motivation to breastfeed: a fit to the opponent-process theory? AB - The opponent-process theory, a dynamic model of acquired motivation presented by Solomon and Corbit (1974), was applied to the process of breastfeeding. A modified form of the Nowlis Mood Adjective Checklist (MACL, Nowlis, 1965, 1970) and a discomfort measure were used in assessing through recall the affective course predicted by the theory. The data were analyzed using multivariate analysis of variance (MANOVA) and correlational procedures. Results were highly significant: Women who breastfed for relatively long periods recalled positive affective responses while the baby was at breast and a subsequent negative or dysphoric response. The additional characteristics of acquired motivation, habituation, and withdrawal, were also evidenced in the data. As a control for possible confounding demand characteristics inherent in the methodology, a sample of childless women was surveyed using an "as-if" form of the same questionnaire. Very little similarity to the breastfeeders was found in the pattern of responses yielded by this group. It was concluded that our major findings are quite likely free of influence from this source. PMID- 4020613 TI - Affective and cognitive characteristics of depression in 10- and 11-year-old children. AB - Indices of emotion experiences, attribution style, and intellectual performance were regressed on an index of childhood depression. The results indicated that the depressed children were like depressed adults in that they reported experiencing a pattern of emotions including sadness, anger, self-directed hostility, and shame, and they tended to explain negative events in terms of internal, stable, and global causes. The similarity between depressed children and depressed adults on these measures was greater for girls than for boys. Depression was not related to performance on a verbal task, but depressed girls performed worse than nondepressed girls on a block design task. The measures of emotion experiences accounted for 78.1% and 46.1% of the variance in girls' and boys' depression scores, respectively, after the variance accounted for by attribution style was partialed out. PMID- 4020614 TI - Type A behavior, age, and psychological well-being. AB - We investigated psychological well-being among Type A and B individuals across the age span. We hypothesized that the hard-driving, achievement-oriented lifestyle exhibited by Type As would be adaptive in younger age groups, but would lead to lower well-being in later life because of increased limitations on the range and level of one's activities. By contrast, the more relaxed, easygoing style of the Type B matches better the slower pace of old age, but is not as conducive to success in younger age groups. Thus we expected older Type Bs more than younger Type Bs to exhibit greater well-being. Results confirmed these hypotheses, but indicated that psychological differences may be mediated in part by differences in physical well-being. Furthermore, experience with life events, and the structure and function of social networks, may contribute to the differences in well-being. PMID- 4020615 TI - Validity of self-reports of alcohol and other drug use: a multitrait-multimethod assessment. AB - Four methods (self-reported rating, self-reported intake, peer-reported rating, peer-reported intake) and multiple analytical criteria were employed to assess the construct validity of reports of three types of substance use (alcohol, marijuana, and cigarettes) in a study of 194 college students who were members of friendship pairs. The resulting multitrait-multimethod matrix was analyzed in the traditional fashion as well as with confirmatory factor analysis. Convergent and discriminant validity for the three substance use traits were quite adequate, although the validity of one measure (the peer-reported intake measure of alcohol use) may be considered inadequate according to some criteria. This study demonstrates the usefulness of multimethod assessment and confirmatory factor analysis for research on construct validity and for derivation of more accurate measures of drug use. PMID- 4020616 TI - Evidence for extending the circumplex model of personality trait language to self reported moods. AB - We show that self-ratings by 141 undergraduates on 17 items form a circumplex that closely agrees with Conte and Plutchik's (1981) circumplex of personality traits. The order of items on a circumplex, generated by self-ratings following a here-and-now instruction set, scarcely differs from that of a circumplex representing the same ratings averaged over a 2-week period. The configuration becomes more elliptical as one moves from the state-like measures (here-and-now ratings) to pure trait measures (averages), but measurement bias is shown to be the most probable cause of the distortion. Allowing for the limitations of small samples of items and raters, the findings show that the circumplex model represents a valid theoretical construct and does not arise from measurement error or from an illusory implicit personality theory. PMID- 4020617 TI - Group decision making by experts: field study of panels evaluating medical technologies. AB - Decision-making processes and their outcomes were investigated in six consensus development conferences at the National Institutes of Health in which panels of experts evaluated new medical technologies. One hundred seventy-seven self administered questionnaires were obtained from participants in these conferences. Questionnaire data were analyzed along with data derived from content analyses of the six consensus statements (CS) produced by the conferences. Results of these analyses provide considerable support for the hypotheses that the quality of the outcome (i.e., the CS) is determined by the existence of an interaction process, a decision procedure, and a chairperson, which facilitate the exchange of relevant information. Strong disagreements among the panelists appear to inhibit such exchange and harm the quality of the CS. Personal satisfaction appears to be more strongly related to the quality of the process and of the information disseminated than to the quality of the outcome. A clear relation was found between the panelists' status and expertise, their participation in the process, and their contribution to the CS. The pattern of these findings is quite similar to that obtained in laboratory studies. The role of preconference organizational factors, such as the selection of conference questions, panel, and speakers, and the characteristics of the technology are discussed. PMID- 4020618 TI - Physiological and affective predictors of change in relationship satisfaction. AB - In 1980, 30 married couples had engaged in a low-conflict and a high-conflict conversational interaction while continuous physiological data were obtained. In a separate session each spouse had provided a continuous self-report of affect while viewing the videotape of the interaction. In 1983, 19 of these couples were re-located to determine the change in relationship satisfaction that had occurred over the preceding 3 years. A broadly based pattern of physiological arousal (across spouses, interaction segments, and physiological measures) in 1980 was found to predict decline in marital satisfaction; the more aroused the couple was during the 1980 interactions, the more their marital satisfaction declined over the ensuing 3 years. Several affective variables also predicted decline in marital satisfaction, including a pronounced sex difference in negative affect reciprocity: Marital satisfaction declined most when husbands did not reciprocate their wives' negative affect, and when wives did reciprocate their husbands' negative affect. PMID- 4020619 TI - [Extra-weak chemiluminescence of drugs. I. Extra-weak chemiluminescence of tablets and capsules]. PMID- 4020620 TI - Binding and disposition of sulfisoxazole in alcoholic cirrhosis. AB - The disposition of sulfisoxazole was studied in six male patients hospitalized with biopsy-proven Laennec's alcoholic cirrhosis and six normal, healthy volunteers. Four of the patients were restudied at a time their liver disease had improved clinically. On the average, compared to the normal group, the metabolism of sulfisoxazole (clearance values with respect to unbound concentration values) appears to be unaltered for the cirrhotic patients. For patients with alcoholic cirrhosis having normal renal function for age and weight, the renal elimination of sulfisoxazole was normal. For those subjects with decreased renal function, the renal clearance of sulfisoxazole appeared to be disproportionately decreased, as evidenced by a lower-than-normal sulfisoxazole renal clearance-to-creatinine clearance values. The apparent steady-state volume of distribution of unbound sulfisoxazole was not altered in cirrhotic patients when compared to normal subjects, while the apparent volume of distribution of total drug increased by more than what could be expected from protein binding changes alone. The elimination rate constant did not differ from values found in normals. These data suggest that the total binding capacity of sulfisoxazole in cirrhotic patients is not different from that of normal subjects. PMID- 4020621 TI - Pharmacokinetics of theobromine and its metabolites in rabbits. AB - The pharmacokinetics of theobromine (3, 7-DMX) and its metabolites was investigated in detail in four male rabbits after bolus intravenous injection (4 mg/kg) of the compound. Apparent first-order rate constants for the metabolic processes involved in the formation of 3,7-DMX metabolites and their excretion in urine were calculated. Theobromine, 7-methylxanthine (7-MX) and 3-methylxanthine (3-MX) were measured in blood and urine, and the other metabolites were determined only in urine. An appropriate model of 14 compartments is formulated to describe the disposition of 3,7-DMX and its metabolites. PMID- 4020622 TI - A theoretical consideration of percutaneous drug absorption. AB - The percutaneous drug absorption process and its clinical significance are not fully known. In this article we propose a theoretical method to obtain two parameters (kd and kc) of percutaneous drug absorption from in vivo data. These parameters are related to diffusion of a drug through the skin and removal process at the skin-capillary boundary, respectively, characterizing several pharmacokinetic aspects of the drug applied to the skin. Moreover, by employing these two kinetic constants, a simulation of percutaneous drug absorption can be theoretically generated. On the basis of our theoretical considerations on the percutaneous drug absorption process described herein, we conclude that the percutaneous drug absorption process is better understood by employing two kinetic constants in a mathematical model and that its clinical application would be highly possible. PMID- 4020623 TI - A nonlinear physiologic pharmacokinetic model: I. Steady-state. AB - The two-compartment model of Rowland et al., (2) has been extended by replacing first order elimination with Michaelis-Menten elimination kinetics. All of the equations for steady-state concentrations and clearances for zero order (constant rate) input orally (into compartment #2) and intravenously (into compartment #1) are derived and reported. The steady-state concentration in compartment #1, following intravenous administration, is shown to be a nonlinear function of maximal velocity of metabolism, Vm, the Michaelis constant, Km, and liver blood flow, Q; and, following oral administration is dependent only upon Vm and Km and is independent of Q. However, oral bioavailability is a function of Vm, Km, and Q. The model allows physiologic pharmacokinetic interpretation of both linear and nonlinear data; and, together with simple modification of the model, can explain much observed pharmacokinetic data to date particularly for first-pass drugs. Future articles in the series will be concerned with single doses, evaluation of literature data in terms of the model, application of the theory in toxicology and in clinical pharmacokinetics and therapeutics. PMID- 4020624 TI - The determination of mean residence time using statistical moments: is it correct? AB - The estimation of mean residence time using statistical moment theory is shown to lead to the true mean residence time only in the case of a concentration-time curve which is a single exponential. In other cases, including the commonly encountered double exponential, there is a systematic error present which can lead to the result being incorrect by as much as a factor of 2. For the case of instantaneous input, an alternative estimation procedure is suggested which gives an estimate much closer to the true mean residence time. PMID- 4020625 TI - Stable-isotope methodology for the bioavailability study of phenytoin during multiple-dosing regimens. AB - With the highly sensitive and specific gas chromatography-mass spectrometry (GC MS), plasma concentrations resulting from an intravenous administration of only a small amount of stable isotopically labeled phenytoin (DPH-d10) were determined to obtain information on the accurate clearance values under steady-state conditions attained with unlabeled phenytoin (DPH-d0). A time course of DPH-d10 concentrations was followed simultaneously with DPH-d0 during dosing intervals by GC-MS, with DPH-d5 as an internal standard. The present stable-isotope methodology offered advantages for the estimation of absolute bioavailability of the oral phenytoin dose in patients, while normal therapy was continued and not withdrawn. PMID- 4020626 TI - Estimation of theophylline clearance during intravenous aminophylline infusions. AB - The utility of predicting theophylline clearance (CL) from two serum concentrations obtained during continuous intravenous aminophylline infusion was examined in 16 stable, adult patients. Blood for theophylline measurement was obtained 0, 6, and 12 h after starting infusions and, thereafter, at 12-h intervals. EMIT was used to assay samples in multiple runs as they were obtained. Later, each sample was reassayed by EMIT within a single run. Bayesian least squares regression and the algebraic method of Chiou were used to predict CL using the 0,6 and 0,12 h concentrations. "Actual" CL was measured by nonlinear least-squares regression of all concentrations obtained during prolonged infusions. Prediction bias and precision were assessed by calculating mean percent error (PCE) and mean absolute percent error (APCE), respectively. A three way repeated-measures ANOVA was used to examine the effect of the method of CL prediction, assay procedure, and time interval between samples on PCE and APCE. Bayesian predictions were less biased and slightly more precise than Chiou predictions. The assay procedure had no effect on bias but precision was improved using a single-assay run. Predictions were less biased and more precise with 0,12 h versus 0,6 h data. Serum samples for theophylline measurement should be obtained after initiating constant intravenous aminophylline and again 8-12 h later in stable, adult patients. Prediction of CL with either of the concentration-based methods studied will then allow safe and rapid adjustment of dosage to achieve therapeutic serum concentrations. PMID- 4020627 TI - Pharmacokinetics of morphine and its surrogates VI: Bioanalysis, solvolysis kinetics, solubility, pK'a values, and protein binding of buprenorphine. AB - The 10-fold greater sensitivity of buprenorphine to fluorescence compared with morphine provides excellent detection for HPLC assay of buprenorphine in biological fluids with a 5-ng/mL sensitivity. Buprenorphine yields a stoichiometric final acid degradation product, a fluorescent-detectable, rearranged demethoxy analogue of buprenorphine, which serves as an excellent bioassay internal standard. Buprenorphine solvolysis is specific-acid and specific-base catalyzed. Alkaline hydrolysis produces no fluorescent products. Acid hydrolysis also produces a fluorescent-detectable, transient dehydro intermediate that is also completely transformed to the demethoxy analogue. The rate constants and Arrhenius parameters for these transformations have been determined. Estimated buprenorphine pK'a values are 8.24 and 10 for the ammonium and phenol groups, respectively. The intrinsic aqueous solubility of neutral buprenorphine is 12.7 +/- 1.2 micrograms/mL at 23 degrees C. The red blood cell plasma water partition coefficients of buprenorphine ranged between 6 and 15. Ultracentrifugation and the red blood cell partition methods led to an estimated 95-98% plasma protein binding. Ultrafiltration and equilibrium dialysis methods were inappropriate because of the high membrane binding of neutral buprenorphine. PMID- 4020628 TI - Topical carbonic anhydrase inhibitors IV: Relationship between excised corneal permeability and pharmacokinetic factors. AB - Ethoxzolamide (1) and two analogues, representing a hydroxyethoxy and a hydrogen substitution on the 6-position of the benzene ring (2 and 3), were applied to rabbit eyes using a topical infusion method designed to provide a constant rate into aqueous humor. Statistical-moment theory was applied to the topical infusion data to describe disposition of each compound within the rabbit eye. For each analogue, it was possible to compare the corneal absorption rate constant (ka), aqueous humor elimination rate constant (k10), disposition mean residence time (MRTd), apparent steady-state volume of distribution (Vdss), and total ocular clearance (Qe). In vivo ocular ka values were related to maximum in vitro corneal penetration rates determined across excised rabbit corneas. In particular, 2 had a much longer residence time and a slower clearance than 1 and 3, which may be responsible for its ability to lower intraocular pressure when dosed topically to the rabbit eye, whereas 1 and 3 show no activity. PMID- 4020629 TI - Protein binding of propisomide. AB - This paper describes the protein binding of propisomide to human serum and isolated proteins using equilibrium dialysis. The drug is exclusively bound to alpha1-acid glycoprotein with high affinity. The binding is saturable even at low concentrations of the drug. Thus, the fraction unbound varied from 0.05 to 0.60 with decreasing serum concentration. The major metabolite of the drug or other drugs with affinity for alpha1-acid glycoprotein can displace propisomide from its binding site only when present in serum at high levels. Two ultrafiltration techniques are compared to equilibrium dialysis for the determination of serum protein binding of propisomide. Ultrafiltration does not give reliable results. Equilibrium dialysis is retained as an accurate method for the determination of the fraction unbound of propisomide. PMID- 4020630 TI - Dissolution rate studies of compression-molded units made from hydroxypropyl cellulose films. AB - Hydroxypropyl cellulose films were prepared by compression molding of three different lots of hydroxypropyl cellulose powder at 149 degrees C, 188 degrees C, and 232 degrees C. Rectangular pieces were cut from these films and viscosity average molecular weight (Mv), degree of orientation, and rate of dissolution were measured. The viscosity average molecular weight (Mv) decreased with increasing processing temperature, while, as expected, the dissolution rate increased. Orientation in the thermoformed units was also evaluated. Correlation of these data with the Mv values suggests that orientation has some controlling influence on the dissolution rate. Because the samples possessing the least orientation were molded at the highest temperature, they also had the lowest Mv due to thermal degradation. Therefore, the effects of molecular weight were not fully separated from orientation effects with regard to control over the dissolution rate. PMID- 4020631 TI - Effects of dose, pH, and osmolarity on nasal absorption of secretin in rats. AB - The effects of dose, pH, and osmolarity on the nasal absorption of a secretin solution were studied in rats. The nasal absorption of secretin was determined by measuring the increased secretion of pancreatic juice, and this was compared with the same response on intravenous administration. The relative bioavailability of secretin on intranasal administration compared with intravenous administration, as estimated from the pharmacological response, was approximately one-tenth. It was enhanced in acid solution and reached a maximum in a 0.462 M sodium chloride solution. PMID- 4020632 TI - Synthesis and pharmacological evaluation of aromatic dihydroxylated spiro[indan 1,3'-pyrrolidine] and spiro[indan-2,2'-pyrrolidine] derivatives. AB - Aromatic hydroxylated derivatives of the spiro[indan-1,3'-pyrrolidine] and spiro[indan-2,2'-pyrrolidine] ring systems have been synthesized and evaluated for dopaminergic agonist and antagonist activities. None of these conformationally restricted catecholamines possessed any dopaminergic activity, but 5,6-dihydroxy spiro[indan-1,3'-pyrrolidine] hydrobromide exhibited weak dopamine antagonist properties. PMID- 4020633 TI - Antifungal properties of 3-n-alkyn-1-ols and synergism with 2-n-alkyn-1-ols and ketoconazole. AB - Twelve 3-n-alkyn-1-ols (C4-C12, C14, C16, and C18) were tested against Aspergillus oryzae, Aspergillus niger, Trichoderma viride, and Myrothecium verrucaria in Sabouraud dextrose agar at pH 5.6 and 7.0. Toxicity to Candida albicans, Candida tropicalis, Trichophyton mentagrophytes, and Mucor mucedo was determined in the same medium at pH 5.6 and 7.0 in the absence and presence of 10% beef serum. Fungitoxicity was strongly influenced by chain length, slightly by pH of the medium, and significantly but not strongly by the presence of beef serum. 3-n-Decyn-1-ol, 3-n-undecyn-1-ol, and 3-n-dodecyn-1-ol were the most active members of the series. Synergism toward C. albicans and C. tropicalis was observed between 3-n-undecyn-1-ol and ketoconazole, and a mixture of 3-n-undecyn 1-ol, 2-n-undecyn-1-ol, and ketoconazole in Sabouraud dextrose agar at pH 7.0 in the presence of 10% human serum. PMID- 4020634 TI - Determination of indeloxazine in plasma by liquid chromatography and gas chromatography-mass spectrometry. AB - Two methods have been developed for the quantitative determination of indeloxazine, a cerebral activator, in plasma by HPLC or GC-MS. After addition of viloxazine as the internal standard, indeloxazine was extracted from alkalinized plasma. In the HPLC method, the plasma extract was treated with 5-dimethylamino-1 naphthalenesulfonyl chloride and analyzed by HPLC with fluorescence detection. In the GC-MS method, the two plasma compounds were converted to their pentafluoropropionyl derivatives for selected-ion monitoring. The limits of detection were 5 and 2 ng/mL for the HPLC and GC-MS methods, respectively. When plasma samples obtained by giving indeloxazine hydrochloride to volunteers were analyzed by the two methods, good correlation between the data was obtained (r = 0.9901). PMID- 4020635 TI - Fluorometric determination of phenylephrine hydrochloride by liquid chromatography in human plasma. AB - A sensitive method is described for the rapid determination of phenylephrine hydrochloride in human plasma. Phenylephrine was analyzed using high-performance liquid chromatography (HPLC) with fluorecence detection at excitation and emission wavelengths of 270 and 305 nm, respectively. A retention time of approximately 4.25 min was observed on chromatograms. Drug was separated from interfering plasma components by the use of disposable solid-phase extraction columns. Linear standard curves were constructed from drug concentrations of 0.5 5.0 and 2.5-80 ng/mL, for which an average recovery of 76-78% was obtained. Phenylephrine could be quantitatively measured at levels as low as 0.5 ng/mL. An assay precision (CV) of 23.6 and 15.9% was obtained at the lower sensitivities of 0.5 and 1.0 ng/mL, respectively. An example of the method was given for analysis of human plasma levels of drug following topical application of two drops of 2.5% aqueous or 10% viscous opthalmic solution to the eyes of two subjects. PMID- 4020636 TI - Contribution of the lung to total body clearance of meperidine in the dog. AB - The potential role of the lung in the disposition of meperidine was examined in six conscious dogs instrumented for measurement of appropriate hemodynamic parameters. Following an intravenous bolus injection of 5 mg/kg, blood samples were collected simultaneously from cannulas placed in the left ventricle and the pulmonary artery, concurrent with the hemodynamic measurements. Pulmonary clearance, calculated from concentration differences between pulmonary arterial and left ventricular blood and pulmonary blood flow, averaged 12.1 +/- 3.70 mL/min/kg, accounting for 58 +/- 13% of the total clearance of the drug. These results help resolve differences between previously reported meperidine clearance in the dog and physiological blood flows and imply that the dog may be a poor model for this drug in humans where clearance is primarily hepatic. PMID- 4020637 TI - Some properties of the USP content-uniformity test as related to control charts and validation of solid dosage forms. AB - The statistical properties of the USP content-uniformity test have been investigated in detail in other reports. This note shows that control charts for the mean potency of a solid dosage form which are constructed using typical individual content-uniformity assays in conjunction with composite assay(s), show tight limits when the product has a high probability of passing the content uniformity test. From a practical point of view, this is a strong argument in favor of the test and recommends the test as a quality control tool. PMID- 4020638 TI - Observations on the dissolution behavior of a tablet formulation: effect of compression forces. AB - Two test drugs, hydrochlorothiazide and phenylbutazone, were separately incorporated into a standard formulation to study their disintegration and dissolution properties as a function of compression force. The increase in dissolution with force was attributed to the manner in which tablets disintegrated while dissolving. At a fixed press setting, tablets from the same compression cycle showed variations in their dissolution which were in agreement with the observed effects of force on dissolution. A linear correlation between dissolution efficiency and the logarithm of force was found to exist over the compression range studied. PMID- 4020639 TI - Effect of vitamin K3 on the first-pass elimination of propranolol in the rat. AB - The effect of vitamin K3, which inhibits electron transfer from NADPH to cytochrome P-450 via cytochrome c reductase, on the metabolism of propranolol was studied in the rat in vitro and in vivo. For in vitro experiments using rat liver microsomes, the metabolism of propranolol was inhibited by vitamin K3. For in vivo experiments, the area under the blood concentration-time curve and the maximum concentration of propranolol were markedly increased following intraportal infusion of propranolol with vitamin K3, but intraportal administration of vitamin K3 had little effect on propranolol kinetics when propranolol was infused intravenously. Thus, it was concluded that vitamin K3 inhibited the first-pass metabolism of propranolol. PMID- 4020640 TI - Graphical approach for determining whether absorption and elimination rate constants are equal in the one-compartment open model with first-order processes. AB - An equation was developed which enables blood level data to be utilized for determining whether or not the first-order absorption and elimination rate constants are equal in the one-compartment open model. This equation was tested using simulated data with excellent results. PMID- 4020641 TI - Hepatic elimination--dispersion model. PMID- 4020642 TI - Absorption potential: estimating the fraction absorbed for orally administered compounds. PMID- 4020643 TI - Radiolabeling of intact tablets by neutron activation for in vivo scintigraphic studies. PMID- 4020644 TI - Pharmacodynamics of the hypnotic effect of salicylamide in rats. AB - Salicylamide (SAM) can produce sedation and sleep in humans and animals. To explore the potential utility of the drug as a research tool for assessing disease effects on the response of the central nervous system to depressant drugs, and to obtain a better understanding of the clinically evident sedative action of SAM, studies were performed to characterize the relationship between the concentrations and hypnotic effect of this drug in rats. Female Lewis rats weighing 170-200 g received SAM by intravenous infusion at a rate of 0.49, 1.22, or 2.47 mg/min until the onset of loss of the righting reflex. This well-defined pharmacological endpoint occurred from 16.7 +/- 2.3 min (fastest infusion rate) to 110 +/- 27 min (slowest infusion rate) after the start of the infusion. SAM concentrations at that time in serum, serum water, brain, and cerebrospinal fluid (CSF) were similar in animals that had received the 1.22- or 2.47-mg/min infusion and lower in animals that were infused at a rate of 0.49 mg/min. The slowest infusion rate group also exhibited increased serum protein binding of the drug. The SAM concentration ratio, CSF-serum water, was essentially unity in all three groups, indicative of rapid equilibration of the drug across the blood-CSF barrier. Gentisamide, the hydroxylated metabolite of SAM, was found in serum, CSF, and brain, but in low concentrations at which this metabolite alone had no hypnotic effect.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4020645 TI - Urinary protein binding, kinetics, and dynamics of furosemide in nephrotic patients. AB - The urinary protein binding, kinetics, and dynamics of furosemide were studied in five nephrotic patients after intravenous dosing. Serial plasma and urine samples containing furosemide were analyzed by HPLC, and drug binding to plasma and urinary proteins was determined using equilibrium dialysis techniques. In comparison to data reported previously in healthy subjects, the steady-state volumes of distribution and nonrenal plasma clearances were significantly increased in nephrotic patients, reflecting the reduced binding of furosemide to plasma proteins. Although there was no significant difference in renal clearance between these two groups, the unbound renal clearance of furosemide was significantly reduced in nephrotic patients even when compensated for by the number of functioning nephrons. Furosemide was extensively bound to urinary protein (19.6-78.4%), and the binding was dependent on the degree of proteinuria. Nevertheless, dose-response analyses, in which the response was represented by sodium excretion rate and the dose by urinary excretion rate of unbound drug, demonstrated that nephrotic patients were less responsive to equivalent amounts of unbound diuretic as compared to healthy subjects. PMID- 4020646 TI - Mechanism of nasal absorption of drugs I: Physicochemical parameters influencing the rate of in situ nasal absorption of drugs in rats. AB - The effect of rate of perfusion, volume, pH of the perfusate, and partition coefficient of the drug on the rate of in situ nasal absorption in rats was examined. The studies showed that the rate constant for the nasal absorption of phenobarbital was independent of the rate of perfusion above a value of 2 mL/min. The nasal absorption of benzoic acid was found to depend on the pH of the perfusate with the benzoate anion being absorbed at a rate one-fourth of that of benzoic acid. The effect of lipid solubility on the extent of nasal absorption was studied using a series of barbiturates. The rate and extent of absorption was found to be dependent on the chloroform-water partition coefficient of the barbiturate. The effect of the volume of the perfusate on the absorption rate constant of phenobarbital, phenol red, tyrosine, and propranolol was studied. The data obtained showed that a linear relationship existed between the rate constants of absorption and the reciprocal of the volume of the perfusate. Using this in situ relationship it was possible to predict in vivo absorption rate constants for propranolol and L-tyrosine when volumes of 0.1 mL were administered. The calculated values for these compounds were found to be close to those determined in in vivo experiments. This indicates that the in situ technique can be used to predict in vivo absorption rate constants. PMID- 4020647 TI - Direct membrane method for the study of interface-controlled transport of cholesterol in aqueous media. AB - Studies were designed to demonstrate the use of a silicone rubber membrane diffusion cell in the mechanistic study of cholesterol mass transfer in aqueous media. The method is shown to be simple, precise, and well suited for delineating conditions which facilitate cholesterol transport. Traditional membrane diffusion resistance was determined with cholesterol solubilized in the nonionic surfactant, polyoxyethylene(10)-nonylphenol ether. The use of a charged surfactant additive, either sodium oleate or benzyldimethyltetradecylammonium chloride, reduced cholesterol membrane flux in a manner consistent with a transport barrier residing in the membrane and micelle interfacial regions. Quantitative determination of total transport resistance was good (CV of greater than 95%) for cases more than 99% interface controlled. Interfacial resistance imparted by the charged surfactant additive was essentially abolished by strong electrolyte (sodium chloride). Electrolyte was utilized in either the upstream or the downstream aqueous compartment to enhance cholesterol transport by a mechanism which is consistent with a marked increase in the frequency of micelle collision with the corresponding membrane surface. When the downstream interfacial component of total transport resistance was "short circuited" by electrolyte in sequential transport runs using the same membrane, a "dumping" of cholesterol by the membrane compartment was observed. Limited studies with a second nonionic surfactant, polyoxyethylene(15)-tridecyl ether, suggest that the structure of separate micelle components may also be related to cholesterol mass transfer which occurs via a micelle collision in the interfacial region. PMID- 4020648 TI - Quantitative analysis of the interfacial barrier to membrane transport of cholesterol solubilized in a charged micellar system. AB - The transport of cholesterol solubilized in polyoxyethylene(10)-nonylphenol ether with benzyldimethyltetradecylammonium chloride additive (4:1, w/w) was studied in a diffusion cell separated by a silicone rubber membrane. Overall kinetics revealed the presence of an interfacial barrier. Additions of NaCl or Na2SO4 abolished the barrier to the extent that total cholesterol flux was essentially limited by membrane diffusion considerations. The results are consistent with the concept of micelles diffusing in an electrical field followed by a collision complex transfer of cholesterol in the aqueous-membrane interfacial region. The electrostatic force of repulsion arises from the overlap of diffuse electrical double layers emanating from the charged mixed micelle and the cationic surfactant adsorbed on the membrane. The influence of surfactant concentration on cholesterol transport kinetics was consistent with electrostatic phenomena. The derived physical model focused on interfacial electrical properties in the donor chamber by maintaining a high concentration (greater than or equal to 0.1 M) of strong electrolyte in the receiver. A linear regression of the logarithm of theoretical transport resistance, total resistance less membrane and receiver boundary layer resistances, versus (ionic strength)1/2 in the donor resulted in a reasonable estimate of the total surface potential of the micelle and membrane surfaces as well as the net dispersion attraction constant. PMID- 4020649 TI - Evaluation of lincomycin as a cholesterol gallstone dissolution rate accelerator. AB - These studies were undertaken to test the hypothesis that interfacial resistance may be an important rate-limiting factor in cholesterol gallstone dissolution. The addition of lincomycin hydrochloride to the gallbladder bile of dogs in an in vitro bath system resulted in an acceleration in the rate of dissolution of a compressed cholesterol monohydrate pellet incubating in the bile. However, the constant infusion of lincomycin for 13 d directly into the gallbladders of conscious, unrestrained dogs, which resulted in biliary lincomycin concentrations comparable to that of the in vitro tests, did not alter the dissolution rate of a compressed cholesterol monohydrate pellet which had been surgically placed into the gallbladder. We therefore conclude that the interfacial resistance between the cholesterol monohydrate pellet and the bile may be reduced by the addition of lincomycin to the gallbladder bile which, in the in vitro environment, results in an acceleration in the rate of dissolution of compressed cholesterol pellets. However, the ineffectiveness of lincomycin in accelerating the dissolution of cholesterol pellets in vivo suggests that interfacial resistance is not the only rate-limiting factor in gallstone dissolution. Other factors, such as mixing, may also be critical. PMID- 4020650 TI - Prediction of solubility in nonideal multicomponent systems using the UNIFAC group contribution model. AB - There is a need to identify suitable blends of solvents to dissolve drugs. Empirical approaches, such as trial-and-error and response surface, require several solubility measurements. In this study the UNIFAC method was used to predict solubility in highly nonideal multicomponent systems in which only the solute enthalpy of fusion and melting point must by measured. UNIFAC combines a group contribution approach with the UNIQUAC model for activity coefficients. Parameters characterizing interactions among constituent groups of a molecule have been previously determined from binary vapor pressure data. These tabulated group parameters are used to predict activity coefficients for newly synthesized compounds. These coefficients, together with the ideal solubility, permit a prediction of solubility. The solubility of 4-hexylresorcinol in ethyl acetate, ethyl myristate, and hexane mixtures was both measured and calculated using UNIFAC. The predicted solubilities were within 10% of the experimental solubilities for all but 3 of 21 mixtures. Since the method accounted for positive and negative deviations from ideality in a hydrogen-bonding system of molecules having different sizes, it shows great potential for use in pharmacy. PMID- 4020651 TI - Preparation and evaluation of microencapsulated and coated ion-exchange resin beads containing theophylline. AB - Anion-exchange resin beads in the theophylline form were prepared and coated with paraffin or encapsulated with ethylcellulose by various methods; one of these products was subsequently coated with paraffin in order to achieve a wide range of release rates and patterns of release. The various products were subjected to rate studies, and it was found that the patterns of release and the rates could be controlled by the cross-linking of the resin and the coating procedures used. A medium and almost constant rate of release was obtained by using ethylcellulose microencapsulation, a coating of hard paraffin, or a combination of both. The amount of coating and the total amount of drug released was also determined. PMID- 4020652 TI - Effect of molecular structure variation on the disintegrant action of sodium starch glycolate. AB - The effect of variation in the degree of cross-linkage and extent of carboxymethylation on the disintegration and dissolution properties of sodium starch glycolate has been examined. Samples of sodium starch glycolate were evaluated for particle size distributions and bulk and tapped densities. The bulk powders were also tested for sedimentation volumes, water uptake, and bulk swelling. Direct compression formulations containing aspirin and hydrochlorothiazide and varying concentrations of the modified starches were tableted on a rotary tablet press and evaluated for weight variation, hardness, disintegration, and dissolution. The results indicate that relatively small changes in molecular structure can cause substantial modification of disintegrant properties and suggest that the specifications for one commercially available sodium starch glycolate are within optimal specifications for both cross-linkage and degree of substitution. PMID- 4020653 TI - Simplex optimization of the blue tetrazolium assay procedure for alpha-ketol steroids. AB - Two independent, simplex procedures were employed to optimize the official blue tetrazolium reaction. The net absorbance for a fixed amount of hydrocortisone was maximized by the simultaneous variation of five factors of the pharmacopeial method, i.e.: concentrations of tetramethylammonium hydroxide, blue tetrazolium, and water, as well as temperature and time for color development. An initial simplex was used to determine an optimum response, while a second was performed to minimize the blank absorbance obtained at the optimum. A series of pharmaceutically important steroids: prednisone, prednisolone, hydrocortisone acetate, and cortisone acetate were also analyzed by the optimized method. The results indicated improvements in sensitivity ranging from 9.27 to 22.95% for the corticosteroids studied. The optimized method also decreased the assay time in relation to the official procedure by one-sixth. PMID- 4020654 TI - Infrared study of the interaction between caffeine and hydroxylic derivatives. AB - The interaction between caffeine and hydroxylic derivatives (phenols, water) has been studied by infrared (IR) spectroscopy in 1,2-dichloroethane. The formation constants, enthalpies, and entropies of complex formation have been determined. The IR spectra in the vOH and vc=o ranges indicate that hydrogen bond formation occurs at the carbonyl functions, approximately 70% of the complexes being formed at the O6 atom. These results are compared with 1,3-dimethyluracil complexes and discussed as a function of the ionization potential of the two oxygen atoms. In the solid hydrate, the spectroscopic results show that the interaction of water takes place on the N9 atom of the imidazole ring in agreement with earlier X-ray results. The different interaction sites in solution and in the solid state are briefly discussed. PMID- 4020655 TI - Liquid chromatographic procedure for the quantitative analysis of megestrol acetate in human plasma. AB - A simple, sensitive, and reproducible high-performance liquid chromatographic (HPLC) procedure was developed for the quantitative analysis of megestrol acetate in human plasma. An internal standard, 2,3-diphenyl-1-indenone, was added to 0.5 mL of plasma followed by extraction with hexane. The residue remaining after evaporation of hexane was reconstituted in methanol and injected onto a mu Bondapak C18 column. The column was eluted with acetonitrile:methanol:water:acetic acid (41:23:36:1), and the eluant was monitored at 280 nm. Megestrol acetate and the internal standard eluted at 6-7 and 12-14 min, respectively. The peak height ratio (megestrol acetate/internal standard) versus plasma concentration was linear over a range of 10-600 ng of megestrol acetate/mL of plasma, and the limit of detection was 5 ng/mL. The mean intra- and interassay accuracies were within 3% of the actual values. The mean intra- and interassay precision, as estimated by RSD, were 4 and 6%, respectively. Constituents in human plasma and megestrol, a possible degradation product, did not interfere in the assay. The procedure was applied to the analysis of plasma samples from subjects receiving 40 mg of Megace q.i.d. PMID- 4020656 TI - Two methods for monitoring the photodecomposition of sodium nitroprusside in aqueous and glucose solutions. AB - The photodecomposition of sodium nitroprusside (SNP) in aqueous and 5% glucose solutions results in the accumulation of cyanide and ferricyanide ions. Methods for the determination of these ions in such solutions have been devised. The continuous-flow method for cyanide involved the generation of cyanogen chloride, ClCN, by oxidation with chloramine T and subsequent reaction of the ClCN with barbituric acid and pyridine to produce a chromophore measurable by spectrophotometry at 580 nm. This cyanide method had a detection limit and sensitivity of 10-12 mumol/L and 1.40 X 10(-3) absorbance units (AU)/mumol/L, respectively, with a working concentration range of 0-800 mumol/L. This method employed mild reaction conditions, pH = 4.1, which rendered it suitable for use in time-course studies of cyanide production from SNP solutions exposed to 366 nm UV light. A simple method for the determination of ferricyanide in SNP solutions was developed which involved the addition of a 1% FeSO4 X 7 H2O in 1% H2SO4 reagent to the SNP solutions under test followed by spectrophotometry at 750 nm. The detection limit and sensitivity of the method were 2-3 mumol/L and 4.05 X 10( 3) AU/mumol/L, respectively, with a working concentration range of 0-100 mumol/L. This method was considered suitable for use as a quality control test of SNP solutions close to the site of their clinical use. PMID- 4020657 TI - Effect of fatty acids and alcohols on the penetration of acyclovir across human skin in vitro. AB - The cutaneous penetration of acyclovir can be significantly increased from a propylene glycol base vehicle by adding small amounts of a polar lipid such as oleic acid. These results are consistent with those found for salicylic acid, and the large increases in acyclovir penetration could potentially lead to better topical treatment of herpes simplex. PMID- 4020658 TI - Binding of dapsone and its analogues to human serum albumin. AB - The binding of dapsone, 4,4'-sulfonylbis(aniline)(1), and its diacetylated derivative, 4,4"'-sulfonylbis(acetanilide)(2), to human serum albumin is reported. To assess the ability of these compounds to displace 4'-[(4 aminophenyl)sulfonyl]acetanilide (3) from albumin, a dialysis rate technique was used. Competition for the bilirubin binding site on albumin was measured with the peroxidase assay. Compounds 1 and 2 strongly displaced both 3 and bilirubin from human serum albumin. The association constants for 1 and 2 with respect to bilirubin binding were 1.29 X 10(3) and 1.15 X 10(4) M-1, respectively. These results suggest that the binding site for 3 and the bilirubin binding site are similar with respect to 1 and 2 and that the binding of dapsone and its derivatives probably does not involve the amino function. PMID- 4020659 TI - Comparison of equilibrium dialysis, ultrafiltration, and gel permeation chromatography for the determination of free fractions of phenobarbital and phenytoin. AB - In this study, three techniques for measuring the free fractions of phenobarbital and phenytoin were compared: equilibrium dialysis, ultrafiltration, and the Hummel and Dreyer method for gel permeation chromatography. In their therapeutic range (15-40 and 10-20 mg/L, respectively) the free fractions of phenobarbital and phenytoin were independent of the drug concentrations. Free fractions of phenobarbital as determined by equilibrium dialysis, ultrafiltration, and gel permeation chromatography were 58.7 +/- 1.8, 58.3 +/- 1.5, and 55.1 +/- 1.7%, respectively. Free fractions of phenytoin were 18.1 +/- 1.1, 17.0 +/- 2.1, and 19.4 +/- 1.2%, respectively. On lowering the albumin concentration, a similar increase in the free fractions of both drugs was observed with all three techniques. The results of this study show that all three techniques are suitable for the determination of free fractions of phenobarbital and phenytoin. Moreover, these techniques seem to be suitable for the investigation of physiological factors that may influence albumin drug binding. PMID- 4020660 TI - Determination of propylene carbonate in pharmaceutical formulations using liquid chromatography. AB - A stability-indicating reversed-phase high-performance liquid chromatographic method using a refractive index detector is described for the determination of propylene carbonate in pharmaceutical formulations. Good precision and accuracy of the method was demonstrated using an aqueous formulation. This method is also applicable to an anhydrous formulation. PMID- 4020661 TI - Effect of lubricant level and applied compressional pressure on surface friction of tablets. AB - A method for measuring friction coefficients of compacted surfaces (tablet surfaces) is described. Frictional coefficient measurements were carried out at various tableting compression forces. The effect of magnesium stearate concentration was found to be a log-linear approach to an asymptote (which would represent a minimum frictional coefficient). PMID- 4020662 TI - Comments on "The ulcerogenic potential of copper aspirinate seems to be more imaginary than real". PMID- 4020663 TI - Swanson great toe flexible hinge endoprosthesis. Design, flexibility, and function. PMID- 4020664 TI - The first cuneometatarsal joint exostosis. Clinical and etiological considerations. PMID- 4020665 TI - Bilateral congenital calcaneocuboid synostosis and subtalar joint coalition. PMID- 4020666 TI - A retrospective analysis of heel pain. PMID- 4020667 TI - Verrucous carcinoma pedis (epithelioma cuniculatum). PMID- 4020668 TI - Superficial spreading melanoma in blacks. A case report. PMID- 4020669 TI - Adult clubfoot. A case report. PMID- 4020670 TI - Pseudorheumatoid nodule versus granuloma annulare. A case report. PMID- 4020671 TI - Fatigue stress fracture of the tarsal navicular. A case report. PMID- 4020672 TI - Reactive arthritis with Yersinia enterocolitica. A case report. PMID- 4020673 TI - Talonavicular coalitions. A review and case report. PMID- 4020674 TI - Effects of picenadol (LY150720) and its stereoisomers on electric shock titration in the squirrel monkey. AB - The mixed-action opioid picenadol (LY150720) is a racemic mixture whose resolution results in a stereoselective separation of agonist and antagonist activity. The effects of picenadol, its dextrorotatory isomer (LY136596) and morphine were studied alone and in combination with naloxone in squirrel monkeys responding under a schedule of electric shock titration. Shock intensity was scheduled to increase at 15-sec intervals in 30 steps from 0 to 5.5 mA. Completion of a fixed ratio 5-response requirement terminated the shock for a 15 sec time-out period after which shock resumed at the next lower intensity. Picenadol (0.1-17.5 mg/kg), the d-isomer (0.3-3.0 mg/kg) and morphine (0.3-5.6 mg/kg) produced dose-related increases in the intensity at which monkeys maintained the shock without decreasing responding in the presence of shock. Shock intensity increases produced by picenadol occurred over a broader dose range than with either the d-isomer or morphine. Increases in shock intensity produced by picenadol, the d-isomer and morphine were blocked by naloxone (0.001 1.0 mg/kg), although the effects of picenadol were less susceptible to antagonism. The effects of the levorotatory isomer of picenadol (LY136595) were also examined alone and in combination with morphine. The l-isomer (0.1-10.0 mg/kg) did not alter shock intensity when administered alone; however, in combination with morphine it produced a dose-dependent antagonism of the effects of morphine. The l-isomer was less potent than naloxone in this respect. These data support previous suggestions that the antinociceptive properties of picenadol arise from mu agonist actions of the dextrorotatory isomer and that the levorotatory isomer acts to limit the efficacy of the racemate. PMID- 4020675 TI - Probenecid impairment of acetaminophen and lorazepam clearance: direct inhibition of ether glucuronide formation. AB - Eleven subjects received acetaminophen (650 mg i.v.) on two occasions in random sequence, with and without concurrent administration of probenecid (500 mg) every 6 hr. Nine subjects similarly received lorazepam (2 mg. i.v.) with and without concurrent probenecid. Acetaminophen half-life was prolonged during probenecid treatment (mean +/- S.E., 4.30 +/- 0.23 vs. 2.51 +/- 0.16 hr; P less than .001) due to markedly decreased clearance (178 +/- 13 vs. 329 +/- 24 ml/min; P less than .001) with no change in volume of distribution (65 +/- 4 vs. 69 +/- 3 l; NS). Urinary excretion of acetaminophen glucuronide during 24 hr was decreased (84 +/- 9 vs. 260 +/- 21 mg of acetaminophen as glucuronide; P less than .001) and acetaminophen sulfate excretion was increased (323 +/- 25 vs. 217 +/- 17 mg of acetaminophen as sulfate; P less than .005) during concurrent probenecid treatment. However, the sum of the two conjugated metabolites was not significantly different (407 +/- 28 vs. 476 +/- 20 mg of acetaminophen as glucuronide plus sulfate excreted per 24 hr; NS). Lorazepam half-life was also prolonged during probenecid treatment (33.0 +/- 3.9 vs. 14.3 +/- 1.08 hr; P less than .001) due to decreased clearance (44.7 +/- 5.4 vs. 80.3 +/- 13.2 ml/min; P less than .001) with no change in volume of distribution (111 +/- 5 vs. 111 +/- 7 l; NS). Formation of the ether glucuronides of acetaminophen and lorazepam is impaired markedly by therapeutic doses of probenecid. Sulfate conjugation is not affected.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4020676 TI - Mechanism of renal lead-binding protein reversal of delta-aminolevulinic acid dehydratase inhibition by lead. AB - The bioavailability of lead in kidney is mediated in part by binding to endogenous high-affinity cytosolic lead-binding proteins (PbBP), which are not detectable in liver. Addition of semipurified 11,500 dalton PbBP to liver delta aminolevulinic acid dehydratase (ALAD) reaction mixtures reverses inhibition of this enzyme by lead and thus provides an explanation for the relative insensitivity of renal ALAD to lead inhibition in vivo and in vitro. This effect results in part from a marked increase in binding of 203Pb to the PbBP relative to control liver cytosol (no PbBP) as demonstrated by Sephadex G-150 gel filtration chromatography. Zinc is known to activate ALAD and is an endogenous component of the PbBP fraction (6 microM in reaction mixtures). Zinc activated hepatic and renal ALAD over a range of 1.5 to 50 microM and also reversed the IC50 lead-inhibited activity. Studies of zinc release and/or displacement from PbBP under ALAD assay conditions (37 degrees C, + glutathione, pH 6.8) were conducted utilizing Sephadex G-25 chromatography. Fifteen to twenty-five percent of the zinc in the PbBP fraction was released, and this value was not markedly influenced by addition of IC50 lead, temperature (4 degrees C) or absence of glutathione; however, zinc release was primarily dependent upon the pH of the reaction mixture. These data indicate that the PbBP fraction attenuates lead inhibition of ALAD in vitro both by chelating lead and apparently serving as a zinc donor for this enzyme under optimal conditions of the ALAD assay. PMID- 4020677 TI - Opioid effects on lidocaine disposition and toxicity in mice. AB - Morphine sulfate, 20 mg/kg, or equivalent doses of the opioids, meperidine and fentanyl, elevated plasma levels of lidocaine after i.v. administration of this antiarrhythmic drug. Plasma levels of the lidocaine metabolites, monoethylglycinexylidine and glycinexylidine, were reduced by opioids as lidocaine levels were elevated. The opioid antagonist, naloxone, 1 mg/kg, reversed the effects of morphine, 20 mg/kg, on lidocaine. After morphine, plasma levels of both lidocaine and indocyanine green were elevated, suggesting that the effect of morphine on lidocaine disposition was related to reduced hepatic blood flow. Morphine and meperidine increased lethality of i.v. lidocaine, as shown by marked reduction of LD50 by either opioid. PMID- 4020678 TI - Augmentation of antibiotic nephrotoxicity by endotoxemia in the rabbit. AB - The acute renal failure complicating bacterial septicemia has multiple potential causes, prominent among which are endotoxemic and antibiotic nephrotoxic injury. Because the toxic interactions of endotoxin and antibiotics cannot be manipulated for study in human disease, we have developed a model of this interaction in the rabbit. Toxicity was assessed by quantification of tubular necrosis and serum creatinine concentrations 48 hr after single-dose i.v. endotoxin and/or antibiotic administration. A minimally nephrotoxic quantity of endotoxin (Escherichia coli lipopolysaccharide 0111:B4, 0.5 mg/kg b.w.) significantly increased the nephrotoxicity of the cephalosporins cephaloglycin (60 mg/kg) and cephaloridine (90 mg/kg) and the aminoglycoside neomycin (60 mg/kg), each of which was mildly-to-minimally damaging by itself. In studies of the acute functional effects of endotoxemia, the lipopolysaccharide had different effects on the renal handling of the two cephalosporins. Endotoxin increased the uptake of cephaloglycin, but decreased uptake of cephaloridine, in renal cortex in the first 0.5 hr after antibiotic administration. However, a prolonged elevation of serum levels of cephaloridine allowed later uptake of toxic amounts of this cephalosporin. Although these findings suggest a role of altered transport in the endotoxin-cephalosporin toxic synergy, the synergy was not reduced when cephaloglycin was given 1.5 hr before the endotoxin, a time which allows substantial elimination of antibiotic before the endotoxemic insult. Studies in another laboratory have demonstrated an endotoxin-induced increase of cortical concentrations of aminoglycosides, which could be a mechanism of the augmented toxicity seen in the present study. It is concluded that endotoxemia causes significant augmentation of the nephrotoxicity of cephalosporin and aminoglycoside antibiotics.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4020679 TI - Dose-dependent sulfoconjugation of salicylamide in dogs: effect of sulfate depletion or administration. AB - The effects of plasma inorganic sulfate concentrations on the dose-dependent kinetics of salicylamide (SAM) were examined in the dog. Decreasing plasma sulfate concentrations from 0.9 mM to less than 0.3 mM significantly decreased clearance of a small dose of SAM (5 mg/kg) to the sulfate conjugate. Infusing sodium sulfate to prevent the decrease in plasma inorganic sulfate concentration that follows a p.o. 20-mg/kg dose of SAM did not increase SAM elimination. However, sodium sulfate given p.o. decreased SAM bioavailability, which suggests a local effect of sulfate on intestinal first-pass metabolism of SAM. These data show some dependence of SAM metabolism on plasma inorganic sulfate concentrations, but only when they are markedly reduced. PMID- 4020680 TI - Reduced hepatic clearance of propranolol induced by chronic carbon tetrachloride treatment in rats. AB - Effect of liver injury induced by chronic treatment with carbon tetrachloride for 1 to 4 months on hepatic clearance of propranolol was investigated in male Wistar rats. Plasma propranolol level after i.v. and p.o. dosing (1.0 mg/kg) was always higher in the rats which were treated for 2 and 4 months than in control (sham injected) rats. The chronic treatment reduced hepatic clearance of propranolol significantly, yielding only approximately 30 to 50% of the control clearance value. Distribution volume of this drug was also significantly reduced by the chronic treatment but seemed to be less sensitive to the treatment than the hepatic clearance. Accordingly, the elimination rate constant was decreased slightly in the rats treated longer than 2 months. The chronic treatment for 2 and 4 months also reduced intrinsic hepatic clearance substantially. The hepatic clearance estimated for both these control and chronically treated rats was significantly dependent on the liver blood flow. Furthermore, propranolol was eliminated much more slowly in the injured liver of the rat which was treated for 2 or 4 months than in the control liver when perfused in in vitro technique. It is, therefore, suggested that the metabolic dysfunction induced by chronic treatment with carbon tetrachloride may be directly related to substantial changes in anatomical arrangement of the hepatic circulation (portasystemic shunting), which may be due to a fibrosis of the tissue. PMID- 4020681 TI - Pharmacological properties of N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7), a calmodulin antagonist in arterial strips from rats and rabbits. AB - Effects of N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7), a calmodulin antagonist on vascular smooth muscle contraction were determined with helically cut arterial strips from rats and rabbits, since adrenergic innervation is quite different between the two species. The pD2 value of W-7-induced relaxation was significantly larger in rat aorta than in rabbit aorta. Treatment of the rabbit aorta with phenoxybenzamine, an alpha adrenoceptor antagonist, augmented the W-7 induced relaxation, whereas in rat aorta there was no such augmentation. Media intimal strips of rabbit aorta showed a larger pD2 value of W-7 as compared to the value seen with whole aorta. The pD2 values of W-7 obtained in phenoxybenzamine-treated and media-intimal strips of rabbit aorta were in good agreement with the value obtained in rat aorta. Aortic strip contraction induced by W-7, which has been demonstrated as a calmodulin-independent effect of this compound, was significantly smaller in rats than in rabbits, suggesting that the relaxation of rabbit aorta induced by W-7 was inhibited by its own contractile effect. W-7 exhibited a typical noncompetitive antagonism against both norepinephrine- and Ca++- (K+-depolarized muscle) induced contractions, and the potency of antagonism was similar between the two agonists. W-7 did not affect 5 min 45Ca incubation value of the K+-stimulated increase in cellular Ca++ content in rabbit aorta, while trifluoperazine, another calmodulin antagonist, and D-600, a calcium antagonist, reduced this value.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4020682 TI - Practolol and its metabolites: tissue localization and retention in the hamster. AB - The disposition of [14C]practolol and its tissue association in the male Syrian hamster were investigated after p.o. administration. After an acute dose of 400 mg/kg, there was a marked persistence in the eye of total radioactivity (primarily practolol; approximate T 1/2 = 7 days) and nonextractable radioactivity which showed minimal decay over 7 days. Nonextractable radioactivity was also found in other tissues (liver, skin, small intestine and skeletal muscle examined). The level of total and nonextractable radioactivity was linearly related to dose (800 mg/kg highest dose examined). There was a marked accumulation of total and nonextractable radioactivity in the eye (7- and 14-fold, respectively) and skin (6- and 7-fold) after daily administration of 400 mg/kg for 22 days. The association of practolol metabolites with tissue macromolecules might explain the immunological changes in patients with the practolol-induced oculomucocutaneous syndrome. The adverse effects of practolol in humans have not yet been reproduced in any laboratory species and so the results must be interpreted with caution in relation to the toxicity of compound. PMID- 4020683 TI - Effects of buthionine sulfoximine on the nephrotoxicity of 1-(2-chloroethyl)-3 (trans-4-methylcyclohexyl)-1-nitrosourea (MeCCNU). AB - Administration of 1-(2-chloroethyl)-3-(trans-4-methylcyclohexyl)-1 1-nitrosourea (MeCCNU; 50-500 mg/kg) to male F344 rats caused a time- and dose-related decrease of glutathione (GSH) preferentially in the liver, but not in the kidney. A 500 mg/kg dose of MeCCNU decreased liver, lung and kidney GSH by 69, 15 and 3%, respectively, 2 hr after dosing. However, MeCCNU had no effect on the ratio of GSH/oxidized GSH or on GSH reductase activity in any tissue tested. A single i.p. dose of DL-buthionine-SR-sulfoximine, an inhibitor of GSH biosynthesis, caused tissue GSH levels to decrease at a rate which reflected the biological half-life of GSH in the respective organs. The T 1/2 for GSH in kidney, liver and lung was found to be 1.5, 5 and 9 hr, respectively. MeCCNU administered s.c. to DL buthionine-SR-sulfoximine-pretreated rats resulted in a depletion of hepatic and renal GSH concentrations which was additive to the effects of either of these treatments alone. DL-Buthionine-SR-sulfoximine also markedly increased the nephrotoxicity of MeCCNU and resulted in a hepatotoxicity not ordinarily seen when MeCCNU was administered alone. These results suggest that a reactive electrophilic intermediate may be involved in the mechanism of MeCCNU nephrotoxicity. Moreover, that renal GSH may play a protective role against MeCCNU-induced nephrotoxicity. PMID- 4020684 TI - Suppression of renal nerve activity by methionine enkephalin in anesthetized rabbits. AB - Endogenous opioid peptides such as Met-enkephalin have diverse physiological actions, which include hypotension and bradycardia in anesthetized animals. The exact sites, the mechanism and the physiological significance of the cardiodepressant effects are not known. The main purpose of this work was to correlate the effect of Met-enkephalin on the rate of sympathetic nerve discharge with its cardiodepressant actions. Anesthetized male rabbits (2-3 kg) were instrumented for the measurement of blood pressure, heart rate, electrocardiogram and multiunit renal nerve activity (RNA). Intravenous administration of norepinephrine (15 micrograms/kg) or phenylephrine (50 micrograms/kg) produced a rapid increase in blood pressure followed by a reduction of RNA and heart rate. Met-enkephalin administered via the same route in doses of 1, 10, 100 and 1000 micrograms/kg initially decreased the RNA and subsequently reduced blood pressure. The above effects of Met-enkephalin were antagonized by naloxone (1 mg/kg i.v.) given 10 min before the peptide. Naloxone methobromide (1.3 mg/kg i.v.), a quaternary derivative of naloxone, did not block the effects of Met enkephalin under identical conditions. These results suggest that the hypotensive effect of Met-enkephalin is secondary to its effects on sympathetic outflow. Lack of naloxone methobromide action is due to its inability to cross the blood-brain barrier and is consistent with a centrally mediated action of Met-enkephalin. PMID- 4020685 TI - Changes in capillary distribution in rat fast muscles following nerve crush and reinnervation. AB - The recovery of muscle weight and contraction tension was measured in rat anterior tibialis muscle following unilateral crushing of the lateral popliteal nerve. Muscle twitch and tetanic tensions and muscle weight had recovered to control values within 6-8 weeks after the nerve was crushed. Capillary supply to each of the four types of muscle fibre present in the intact muscle, and within the groups of adjacent fibres of similar histochemical reaction for succinate dehydrogenase and myofibrillar actomyosin ATPase found in the reinnervated muscle, was computed by the method of Gray & Renkin (1978). Capillary area density (capillaries/mm2) within the grouped regions of the reinnervated muscle was not significantly different from the supply to the same fibre type in intact contralateral muscles. Capillary/fibre ratio for the more glycolytic fibre types (alpha W, alpha?) was lower than in intact muscle, while the values for both alpha R and beta R oxidative fibres agreed closely with control values. It seems that selective growth and loss of capillaries occurs during reinnervation, adjusting capillary supply to meet the changed metabolic demands of the individual fibres following regrouping. PMID- 4020686 TI - The respiratory activity of human levator costae muscles and its modification by posture. AB - The activation of the levator costae, a set of axial muscles inserted between each rib and the vertebra immediately rostral, has been studied electromyographically in a human subject, standing upright, with head erect ('neutral' posture). Caudal levator costae muscles (T9, and T10) are active during eupnoea. Periodic activity in phase with inspiration occurs in admixture with different levels of tonic activity that is strongly influenced by posture. Postural changes and various voluntary respiratory manoeuvres which should lengthen or shorten the levator costae muscles increase and decrease, respectively, their activity in the 'neutral' posture. The tonic activity was most readily enhanced by contralateral flexion of the spine, and this could bring to threshold phasic activity not otherwise present. Conversely, ipsilateral flexion could abolish both phasic and tonic components. Active expiratory efforts and static voluntary relaxation of the respiratory muscles could diminish or abolish levator costae activity. Paradoxically, chest-directed inspiratory efforts maintained at elevated lung volume with open glottis could also diminish or abolish levator costae activity. We attribute this to shortening of the levator costae muscles and unloading of their muscle spindles by the elevation of the ribs due to the action of the external intercostal and parasternal muscles. The results are discussed in relation to the mechanical coupling between the diaphragm and the lower rib cage; emphasis is given to the possible independent motions of the lower two or three ribs and the abductor action of their corresponding levator costae muscles, based on anatomico-physiological considerations. PMID- 4020687 TI - Influence of human muscle length on fatigue. AB - The effect of muscle length on susceptibility to fatigue has been examined in human ankle dorsiflexor muscles. The fatiguing procedure consisted of either indirect tetanic stimulation at 20 Hz or maximal voluntary contraction; each procedure lasted 90 s. The amplitude of the evoked muscle compound action potential (M-wave) increased during the first 30 s or so of the tetanic fatiguing procedure and then decreased. The torque developed by the dorsiflexor muscles declined throughout the period of tetanization. A significantly greater reduction in twitch and tetanic torque was found after the fatiguing procedure had been conducted at the optimum muscle length rather than with the muscle in a shortened position. Relaxation after tetanic stimulation was slower after fatigue had been induced at the optimum muscle length. It is concluded that muscle fatigue is related to the number of actin-myosin cross-bridge interactions and is unlikely to be accounted for solely on the basis of changes in the ionic composition of the transverse tubular fluid. PMID- 4020688 TI - The transport of sugars across the perfused choroid plexus of the sheep. AB - The blood-perfused choroid plexuses from the lateral ventricles of the sheep were used to determine the nature of sugar exchanges between blood and cerebrospinal fluid (c.s.f.). There was a net entry of sugars from blood to c.s.f. at all concentrations of sugars which were used and this net entry was seen when the sugars were measured either directly by enzymic analysis or by the use of isotopically labelled sugars. From competition experiments the order of affinity of the transporting system from both blood to c.s.f. and c.s.f. to blood was the same, i.e. 2-deoxy-D-glucose much greater than D-glucose greater than 3-O-methyl D-glucose much greater than D-galactose. The transport of sugars from c.s.f. to blood and blood to c.s.f. consists in both cases of a non-saturable and a saturable component. However, the affinity of the two systems is markedly different, the blood to c.s.f. being a system of low affinity and high capacity while that of the c.s.f. to blood has a high affinity and a low capacity. The concentration of glucose in the newly formed c.s.f. was estimated from the rate of c.s.f. secretion and the net flux of glucose across the choroid plexus. The concentration of glucose in this fluid was some 45-60% of that in plasma and so the low glucose concentration observed in bulk c.s.f. would appear to be a result of the entry process and not that of cerebral metabolism. PMID- 4020689 TI - Effect of ventricular tonicity upon cerebrospinal fluid production in rabbits. AB - Ventriculo-cisternal perfusion in rabbits has been employed to examine steady state relations between ventricular sodium and water fluxes and ventricular osmolality. These fluxes have been determined in individual rabbits when the ventricular fluid was either similar to normal cerebrospinal fluid (c.s.f.) or when its osmolality was changed to one value within the range of about 150-300 mosmol/l. The ventricular osmolality was changed by perfusing the ventricles with sucrose solutions of different concentrations that were either ion free, contained a low concentration of sodium, or contained both sodium and furosemide to inhibit the active production of c.s.f. Results suggest that this experimental range of ventricular osmolality is without significant effect upon a constant active sodium-coupled water movement into the ventricles, whereas a passive osmotic water flux into the ventricles increases with ventricular osmolality. PMID- 4020690 TI - Effects of stimulation and diphenylhydantoin on the intracellular sodium activity in Purkinje fibres of sheep heart. AB - The effects of stimulus frequency on the intracellular Na+ activity (aiNa) of Purkinje fibres from sheep hearts have been investigated using ion-sensitive micro-electrodes. aiNa increased by approximately 44% at 3 Hz and approximately 6.5% at 0.2 Hz. The size of the increase was very variable between preparations and did not appear to be related to the initial level of aiNa before stimulation. During stimulation, the rise of aiNa was exponential and gave a new steady-state level within about 15 min. The time constant of this rise was independent of the frequency of stimulation. The recovery of aiNa following a period of stimulation also appeared to be exponential but the time constant was dependent upon the extent to which aiNa had been raised during stimulation, with shorter time constants following larger rises. The effects of stimulation on aiNa were compared to inhibition of the Na+-K+ pump using high concentrations of cardioactive steroids. The influence of diphenylhydantoin (DPH) on the Na+ permeability of the cell membrane was assessed by measuring the rate of rise of aiNa following Na+-K+-pump inhibition. DPH decreased the rate of rise of aiNa by approximately 37% at concentration of 10(-4) M. The decrease of Na+ permeability produced by DPH is probably responsible for the observed reduction of aiNa in quiescent preparations. DPH also produced substantial decreases of aiNa in stimulated preparations. These results are discussed in relation to its known anti-arrhythmic effects. PMID- 4020691 TI - A dopaminergic receptor modulates catecholamine release from the cat adrenal gland. AB - Nicotine evokes the release of catecholamines from perfused cat adrenal glands in a concentration-dependent manner, the median effective concentration for nicotine being 5 microM. Two 2 min pulses of 5 microM-nicotine, 40 min apart (S1 and S2) gave net catecholamine outputs of 7.64 and 3.55 micrograms/8 min, respectively. The ratio S2/S1 in control glands was 0.5. Increasing concentrations of apomorphine (1-10 microM) markedly inhibited catecholamine release during the second nicotine pulse (S2). At 1 microM-apomorphine, the release during S2 was significantly reduced to 16% of S1; with 10 microM-apomorphine, the secretory response was reduced further to only 3% of S1, the ratio S2/S1 being 0.03. The presence of haloperidol, sulpiride or picobenzide (each 0.5 microM) during S2, completely reversed the inhibition of catecholamine release produced by apomorphine. Haloperidol itself increased the nicotinic secretory response during S2; so, while the ratio S2/S1 was 0.5 in control conditions, this ratio increased significantly to 0.95 if haloperidol (0.5 microM) was present during S2, suggesting that the presence of this dopaminergic antagonist removed a negative feed-back mechanism that inhibits nicotine-evoked catecholamine release. If present during S2, dopamine (1 microM) also markedly inhibited catecholamine release evoked by nicotine; this inhibition was again reversed by 0.5 microM haloperidol. Neither the opiate antagonist naloxone nor the alpha-adrenoceptor blocking agent phentolamine (at concentrations of 0.5-5 microM) affected the inhibition by apomorphine of the secretory response to nicotine. These data strongly suggest that the cat adrenal medulla chromaffin cell membrane contains a dopaminergic receptor which modulates the catecholamine secretory process triggered by stimulation of the nicotinic cholinoceptor. The fact that dopamine is released in measurable amounts, together with adrenaline and noradrenaline, from perfused cat adrenal glands in response to nicotinic stimulation (V. Cena, unpublished results), favours a role for this dopaminergic receptor in modulating catecholamine release from the chromaffin cell. PMID- 4020692 TI - Effects of readmission of substrate on the membrane potential in glycogen depleted guinea-pig taenia coli. AB - In the glycogen-depleted smooth muscle of the guinea-pig taenia coli, application of glucose or beta-hydroxybutyrate (beta-HB) in the presence of 20 mM-K or carbachol (5 microM) produced a transient hyperpolarization for about 1 min followed by a sustained depolarization accompanied by spike activity. The early hyperpolarization was highly temperature dependent, so that below 30 degrees C, substrate application produced the depolarization with a delay of approximately 2 min, without a clear preceding hyperpolarization. The responses to substrate were not affected by ouabain (10 microM). Readmission of K after a treatment with K free solution for 10 min caused a transient hyperpolarization only in the presence of substrate. This hyperpolarization was abolished by ouabain. Verapamil (0.1 microM) blocked the substrate-induced depolarization, revealing an underlying slow hyperpolarization. Removal of Ca abolished both the hyperpolarization and depolarization caused by substrate application, but the hyperpolarization disappeared much more slowly than the depolarization. Removal of the external K had little effect on the substrate-induced hyperpolarization, but the hyperpolarization induced by substrate application was increased when the external K was increased up to approximately 20 mM. Both the hyperpolarization and the depolarization were not clearly affected by completely replacing Na with choline. The results suggest that ATP supplied by the addition of substrate activates some electrogenic pump, probably a Ca pump, causing hyperpolarization, and that ATP also removes the inactivation of Ca conductance with some delay, resulting in an increased depolarization. PMID- 4020693 TI - Action and localization of glycine and taurine in the cat retina. AB - The effects on retinal ganglion cells of iontophoretically applied glycine, taurine and strychnine were studied in the optically intact eye of the cat. Glycine and taurine suppressed the light-evoked discharge of all on-centre and off-centre brisk ganglion cells, regardless of the visual stimulus used. Strychnine blocked the action of externally applied glycine and taurine. The light-evoked response of all ganglion cells was raised by strychnine. The tonic discharge of the light response was suppressed or raised by the drugs more than the phasic response. A population of amacrine cells, which was heavily labelled by [3H]glycine, did not take up [3H]taurine. [3H]taurine was only weakly accumulated by inner nuclear layer neurones and was predominantly located in the outer retina. PMID- 4020694 TI - Changes in sodium activity during light stimulation in photoreceptors, glia and extracellular space in drone retina. AB - Ion-selective micro-electrodes were used to measure Na+ activity, aNa, in the two types of cell, photoreceptors and glial cells, and in the extracellular space, in superfused slices of the retina of the honey-bee drone, Apis mellifera male. Movements of Na+ were induced by light stimulation, or by increasing [K+] in the superfusate. In the dark, aNa in the photoreceptors was 10 mM (S.E. of the mean = 1 mM); in the glial cells it was higher: 37 +/- 2 mM. We estimate that in this preparation about 2/3 of the free Na+ in the tissue is in the glial cells. Stimulation with a train of light flashes, 1 s-1 for 90 s caused aNa in the photoreceptors to increase by 16 +/- 2 mM. K+ activity, aK, decreased by 21 +/- 3 mM. During the standard train of light flashes, aNa in glial cells decreased by only 1.5 +/- 0.3 mM, much less than the increase in aK (7 +/- 2 mM). One possible interpretation of this result is that most of the increase in aK is due to K+ uptake by a mechanism other than Na+-K+ exchange. In extracellular fluid, stimulation caused aNa to fall to a relatively steady value in about 10 s. Unlike aK, there was no tendency for aNa to return to the base line during the remainder of the 90 s stimulation. The fall in aNa was 14 +/- 1 mM: a greater fall is prevented by extracellular electric currents and a decrease in extracellular volume. When [K+] in the superfusate was increased from 7.5 to 18 mM, aNa decreased in the glial cells but not in the photoreceptors. In this tissue, stimulation causes changes in aNa in the neurones that might be large enough to modify the biochemistry of the cells. But in the glia, the fractional changes are small. PMID- 4020695 TI - Three serial neurones in the innervation of the colon by the sacral parasympathetic nerve of the dog. AB - Electrophysiological and histological techniques were used to study the nature of the innervation of the colon by the sacral parasympathetic nerve of the dog. Many cells which incorporate horseradish peroxidase (HRP) were observed in ganglia of the pelvic plexus, but not in the sacral cord, after HRP was injected into the wall of the distal colon. Stimulation of the pelvic ganglia by an application of dimethylphenylpiperazinium contracted the distal colon. The contraction was reduced by nicotine applied to the colon. Compound action potentials in responses of rectal strands of the pelvic nerve to stimulation of the sacral ventral roots decreased or disappeared after hexamethonium bromide (C6) was applied to the pelvic plexus. Conduction velocities of the potentials showed that most of the preganglionic fibres were B fibres, and nearly all the post-ganglionic fibres were C fibres. Many C fibres were observed by electron microscopy in the rectal strands after degeneration of the pelvic and hypogastric nerves. Stimulation of such rectal strands caused a contraction of the colon, which diminished after C6 was applied to the distal colon. These results show that the sacral parasympathetic nerve innervating the colon comprises three serial neurones located in the sacral spinal cord, the pelvic plexus and the myenteric plexus. PMID- 4020696 TI - Characteristics of the vagally driven non-adrenergic, non-cholinergic inhibitory innervation of ferret gastric corpus. AB - This paper reports a quantitative in vivo study on the vagal activation of the intramural non-adrenergic, non-cholinergic inhibitory nerves in the ferret gastric corpus. The nature of the inhibitory neurotransmitter was also investigated. In the atropinized, guanethidine-treated, urethane-anaesthetized ferret, electrical stimulation (10 s at 20 V, 1-20 Hz, 0.5 ms pulses) of the cervical vagi produced a prompt fall in intracorpus pressure that was related to the stimulus frequency. The maximal response was achieved at 10 Hz. The time taken for the intracorpus pressure to return to pre-stimulus levels after a 10 s period of stimulation was related to the stimulus frequency; at 10 Hz the pressure took approximately 11 min to recover. In contrast to studies in the cat (Martinson & Muren, 1963), there was no detectable difference in the electrical threshold for activation of the vagal excitatory and vagal inhibitory fibres. The nature of the vagal non-adrenergic, non-cholinergic inhibitory neurotransmitter was investigated using a variety of antagonists and agonists. Adenosine triphosphate (ATP), adenosine, alpha beta-methylene ATP and beta gamma-methylene ATP all contracted the corpus in the presence of vagotomy, atropine, guanethidine and indomethacin. The vagally induced fall in corpus pressure was not blocked by high doses of alpha beta-methylene ATP. A variety of peptides were investigated for their effects on corpus pressure in the presence of atropine, guanethidine and vagotomy. Bombesin, pentagastrin, substance P, cholecystokinin octapeptide (CCK-8) and bradykinin all produced an increase in intracorpus pressure. Neurotensin and vasoactive intestinal polypeptide (VIP) both decreased intracorpus pressure, and of the two VIP most closely mimicked the response to vagal activation of the non-cholinergic, non-adrenergic inhibitory neurones. The results provide support for the involvement of a peptide (possibly VIP) rather than a purine in the vagally driven decrease in intracorpus pressure in the ferret. PMID- 4020697 TI - Electroretinograms evoked by sinusoidal excitation of human cones. AB - The amplitude and phase of the fundamental Fourier component of the human electroretinogram (e.r.g.) were recorded with a synchronous detection method under conditions in which each of the three species of cones can be assumed most sensitive in turn. Weber-Fechner behaviour is well established at, or more distal in the retina than, the source of these voltages. Results over the frequency range 7-50 Hz exclude a diffusion model of human flicker perception. The e.r.g. phase vs. frequency plot found with a 'red' test differs from that obtained with a 'green'. The shapes of the e.r.g. field sensitivity action spectra agree with those of the subject's IIj(mu) (j = 3, 4 and 5) mechanisms of Stiles and with in situ measurements of the absorbance spectra of human cone pigments. Threshold phase with each test was independent of background wave-length but, consistent with the results in 3, the phase of the response to the 'red' test (25 Hz) differed significantly from that to the 'green'. If these differences resulted from the absorption of test photons of different colours at different points along the outer segment (independent of cone spectral sensitivity), they would be as clear on dichromats as on trichromats. Results on a protanope are inconsistent with this prediction. We infer that differences in phase are due to the different kinetics of different cone mechanisms and that the e.r.g.s studied here are evoked by exciting only the most sensitive cone mechanism, even though dark adaptation studies prove that at e.r.g. threshold the test is well above psychophysical threshold for all three cone species. If the inference in 5 is correct, studies of sensitivity across the retina suggest that the spatial distribution of long-, middle- and short-wave-sensitive cones in the human retina differ remarkably. PMID- 4020698 TI - The luminance origin of the pattern electroretinogram in man. AB - Electroretinograms (e.r.g.s) and visually evoked potentials (v.e.p.s) to pattern stimuli were recorded simultaneously from healthy subjects. The stimuli were produced by a configuration in which the luminance of two sets of spatial elements (checks) could be modulated independently. Experiments were designed to distinguish between contrast responses and non-linear luminance responses. In the first of two basic experiments, the luminance of only one set of checks was modulated, at a constant level in every trial. The other set was not modulated, but its luminance was set at various levels. Under these conditions the local luminance stimulation was kept equal for every trial whereas the contrast stimulation varied. Therefore, local luminance responses in these experiments were expected to be constant and contrast responses were expected to vary. The e.r.g.s were identical for all luminance settings of the unmodulated checks, suggesting that luminance rather than contrast determines the response. The v.e.p.s showed, on the contrary, the behaviour expected for contrast responses. In the second basic experiment the local luminance stimulation was also kept constant, but the phase difference between the modulations of the two sets of checks was varied between 0 deg (pure luminance stimulation) and 180 deg (pattern reversal). In this type of experiment the second harmonic responses to local luminance modulation are expected to decrease to a minimum as phase difference goes from 0 to 90 deg and increase again as phase difference goes to 180 deg. Contrast responses are expected to increase monotonically from zero to maximal at phase difference shifts from 0 deg (no contrast stimulation) to 180 deg (contrast reversal). The e.r.g.s decreased to a minimum at 90 deg phase difference and increase again with phase difference going to 180 deg. At 0 and 180 deg the same value was recorded. Consequently, the e.r.g. behaviour suggests a luminance origin of the responses. The v.e.p.s monotonically increased as phase difference went from 0 to 180 deg, thus suggesting a contrast origin of the responses. Two additional control experiments were performed. The first experiment compared the responses to homogeneous field red/green exchange and pattern red/green exchange, with the luminances of the red and green sources matched by heterochromatic flicker photometry. The exchange of luminance-matched red and green checks (pattern reversal) did not produce different e.r.g. responses from those recorded in response to homogeneous field red/green exchange. The v.e.p. showed a significant increase for the pattern stimulus.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 4020699 TI - Hypothalamic thermosensitivity in capsaicin-desensitized rats. AB - In rats, we tested the hypothesis that capsaicin desensitization reduces hypothalamic warm thermosensitivity. We locally heated and cooled the hypothalamus using water-perfused thermodes while observing thermoregulatory variables. In untreated rats, a small dose of capsaicin had profound effects on thermoregulation. However, desensitizing rats to capsaicin had no effect on hypothalamic thermosensitivity for metabolic rate or changes in body temperature due to displacements of hypothalamic temperature. Contrary to current opinion, we conclude that capsaicin desensitization does not alter hypothalamic thermosensitivity to warm or cold. PMID- 4020700 TI - Modulation of slow response excitability by calcium in rabbit atrial trabeculae. AB - Slow responses were induced in rabbit isolated left atrial trabeculae in a modified Tyrode solution containing 15 mM-KCl and 1 mM-BaCl2. Conventional electrophysiological techniques were employed for stimulating and recording membrane potentials. Under these conditions, the excitability of the slow response depends on the past excitatory history of the preparation. As the stimulation frequency increases (range: 0.08-1 Hz) for a conditioning period of stimulation, the excitability of the slow response increases. This can be demonstrated by a decrease in stimulus requirement necessary to maintain slow response excitation following the conditioning period of stimulation. It is shown that when extracellular Ca2+ concentration is reduced to 0.5 mM, that phenomenon of frequency-dependent slow response excitability disappears but slow responses can still be elicited. Also, the addition of D-600 to 2.7 mM-Ca2+ solutions depresses both the slow response and its frequency-dependent excitability. The absence of frequency-dependent slow response excitability is not related to the depression of the slow response upstroke caused by low-Ca2+ solutions. Increasing intracellular Ca2+ concentration by exposing the preparation to low-Na+ solutions or to ouabain did not revert the observed effects in low-Ca2+ solutions. The addition of substances (5 mM-caffeine or 0.35 microM-adrenaline) that potentiate the influx of Ca2+ in low-Ca2+ solutions was found to be effective in restoring the dependence of slow response excitability on the frequency of stimulation. The increase in extracellular Ca2+ above 4 mM depressed the excitation of the slow response. Above 5.4 mM-Ca2+, the excitation of the slow response was completely inhibited while the preparation displayed continuous oscillations in transmembrane potential. The presence of a subthreshold response (subliminal response) that precedes and triggers slow response excitation is accompanied by tension development. Since the subliminal response is responsible for the changes in slow response excitability it is proposed that the Ca2+ inflow during slow response electrogenesis modulates the excitability of the slow response. Two possible physiological implications for this finding are discussed. PMID- 4020701 TI - Pyramidal effects in dorsal neck motoneurones of the cat. AB - The effects of contralateral pyramidal stimulation have been investigated with intracellular recording from cat alpha-motoneurones that innervate the dorsal neck musculature. A short train of stimuli evoked three types of synaptic effects: predominant excitation or inhibition and mixed effects characterized chiefly by early excitation followed by inhibition. Latency measurements indicated a minimal disynaptic linkage for excitation and for inhibition. Splenius motoneurones received primarily excitation whereas biventer cervicis complexus motoneurones received a more varied input characterized by mixed effects or inhibition. Following transection of the pyramid just rostral to the decussation (lower pyramidal lesion) pyramidal stimulation above the lesion still produced disynaptic excitation and longer latency (possibly trisynaptic) inhibition. Pyramidal stimulation just caudal to this transection evoked inhibition with a minimal disynaptic latency, as well as longer latency excitation. The incidence of longer latency excitation was found to be reduced in cats with corticospinal tract transections at the level of the second cervical spinal segment. No post-synaptic potentials were evoked by pyramidal stimulation rostral to a pyramidal transection at the level of the trapezoid body. It is suggested that disynaptic excitation evoked by pyramidal stimulation above the lower pyramidal lesion is mediated by medullary reticulospinal neurones possessing monosynaptic excitatory connexions with neck motoneurones. Longer latency excitation appears to be mediated by neurones that receive corticospinal tract input and are located in the spinal segments containing the neck motoneurones. Disynaptic inhibition is mediated by neurones likely to be situated between the second cervical spinal segment and the level of the lower pyramidal lesion. The results also suggest that the first neurone in the chain mediating longer latency inhibition is located in the brain stem. The differences in pyramidal synaptic input between splenius and biventer cervicis-complexus motoneurones are considered in relation to the roles these muscles may serve in head position control. PMID- 4020702 TI - Renal extraction and clearance of p-aminohippurate during saline and dextrose infusion in the rat. AB - The reliability of the use of p-aminohippurate (PAH) as a clearance marker for the determination of renal plasma flow during saline or dextrose infusion was investigated in conscious and anaesthetized rats. In the conscious rat (wt. 350 400 g) infused for 4 h with 0.85% saline followed by 3 h of 2.5% dextrose, PAH clearance averaged 11.50 +/- 1.45 ml/min during saline infusion and 7.83 +/- 0.82 ml/min during dextrose infusion. The difference was significant (P less than 0.02). Inulin clearance, however, was unchanged. With dextrose as the initial infusate, PAH clearance averaged 5.86 +/- 0.65 ml/min and increased (P less than 0.01) to 8.74 +/- 0.71 ml/min following a change of infusate to saline, although inulin clearance was again unchanged. In separate groups of rats anaesthetized with sodium pentobarbitone, a comparison was made between renal blood flow values calculated from PAH clearance and haematocrit, and those determined simultaneously using an electromagnetic flow probe placed on the left renal artery. During 0.85% saline infusion, the calculated value was 88.1 +/- 8.4% of that measured using the flow probe. During 2.5% dextrose infusion the value determined from PAH clearance was only 47.3 +/- 4.2% of that obtained using the flow probe, and this is significantly (P less than 0.01) lower than the ratio found during saline infusion. In another study, renal venous blood samples were obtained from sodium-pentobarbitone-anaesthetized rats during 0.85% saline or 2.5% dextrose infusions, for calculation of the renal PAH extraction ratio. During saline infusion, PAH extraction averaged 68.3 +/- 2.5%, whereas during dextrose infusion PAH extraction was lower (P less than 0.001) and averaged only 48.8 +/- 3.2%. It is concluded that PAH clearance grossly underestimates renal plasma flow during 2.5% dextrose infusion in the rat. PMID- 4020703 TI - Naloxone increases blood flow in the human hand. AB - Intravenous injection of 2 mg naloxone produced a rapid and pronounced rise of blood flow (6.3 +/- 5.0 to 67.0 +/- 15.1 ml min-1 100 ml-1) and skin temperature (28.3 +/- 3.0 to 32.4 +/- 1.2 degrees C) in the finger and hand of seven of ten normal volunteers. In the other three there was only a small response. Skin temperature did not change in either the face or the foot. Three responding subjects who were retested with 0.4 mg naloxone showed a smaller and briefer response. To exclude a local effect of naloxone on skin blood flow due to release of histamine, responders and non-responders were tested with naloxone and morphine pricked into the skin of the hand and forearm. All showed a weal and flare reaction to morphine which was not abolished by mixture with naloxone; none showed any reaction to naloxone alone. These results suggest that, in some subjects at least, skin blood flow in the hand may be under endogenous opioid control and they raise the possibility that opioid antagonists might have value in the treatment of disorders of skin blood flow such as Raynaud's disease. PMID- 4020704 TI - Different types of slowly conducting afferent units in cat skeletal muscle and tendon. AB - In chloralose-anaesthetized cats, the impulse activity of single afferent units conducting at less than 30 m s-1 and having receptive fields in the triceps surae muscle or the calcaneal tendon, was recorded from thin filaments of the dorsal roots L7 and S1. The receptive fields of the units were tested with a variety of graded natural stimuli (local pressure, stretch, contractions, temperature changes). In addition, the algesic agent bradykinin was injected into the receptive fields, but the sensitivity of the receptors to this substance was not used for classification purposes. Four types of receptors could be distinguished using the strongest response to innocuous natural stimulation as the criterion for characterizing a given ending: (a) nociceptors showing no response to innocuous forms of stimulation and requiring noxious (tissue-threatening) stimuli to be clearly activated; (b) low-threshold pressure-sensitive receptors responding to innocuous indentation of the tissue but being relatively insensitive to stretch and contractions; (c) contraction-sensitive receptors reaching high discharge frequencies during active contractions of moderate force and innocuous stretch, but being relatively insensitive to local pressure stimulation; (d) thermosensitive receptors responding strongly to small changes in temperature without reacting to innocuous mechanical stimulation. The possible involvement of the different receptor types in central nervous functions (nociception, mechanoreception, ergoreception, thermoregulation) is discussed. PMID- 4020705 TI - Post-natal development of pyramidal tract neurones in kittens. AB - The post-natal development of pyramidal tract neurones (p.t.n.s) was investigated in twenty-one barbiturate-anaesthetized kittens from birth to 28 days of age using a combination of electrophysiological and anatomical techniques. P.t.n. responses were recorded intracellularly as well as extracellularly with glass micropipettes filled with horseradish peroxidase (HRP) on stimulation of the medullary pyramid and cerebellar nuclei. Latency histograms of antidromic responses of p.t.n.s were compared at various ages. In the neonate, p.t.n.s were divided into two groups which were presumed to be analogous with fast and slow p.t.n.s in adult animals. During the first post-natal week, latency shortening was not conspicuous, but by the end of the second post-natal week, the faster group showed a marked decrease of latencies (up to around 10 ms at 14 days of age), while those of the slower group did not change so much. The slower group increased their conduction velocity during the third post-natal week (latencies up to around 18 ms). At the end of the fourth post-natal week, the distribution of antidromic latencies was in a narrower range, but the values were still longer than those reported in adult animals. Intracellular HRP staining revealed that apical dendrites of p.t.n.s spread fully to the pial surface even at birth. The somata of these neurones were characteristically covered with somatic appendages and development of the basal dendritic tree was immature in 0-1-day-old kittens. Basal dendrites developed nearly completely by 7 days, but somata were still covered with appendages. During the fourth post-natal week, these appendages disappeared almost completely. The sizes of the dendritic field, especially of apical dendrites, became larger in parallel with the development of cortical layers. From the morphological point of view, differentiation of fast and slow p.t.n.s was not clear until 28 days of age except in somatic volumes, which were already different in the first post-natal week. At the end of the fourth post natal week, p.t.n.s with short antidromic latencies had a tendency to bear spines more sparsely over the secondary and tertiary dendritic surface in comparison with p.t.n.s with longer latencies. Intracortical axonal trajectories developed fairly well in the immature cerebral cortex, and the general pattern of ramification changed little during the first month after birth.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 4020706 TI - Reciprocal inhibitory interneurones in the Xenopus embryo spinal cord. AB - The mechanism of reciprocal inhibition between antagonistic motor centres during swimming in the paralysed Xenopus embryo has been investigated further. Paired intracellular recordings have been made from interneurones and motoneurones in an attempt to identify neurones which make direct inhibitory synapses onto motoneurones on the opposite side of the spinal cord. A physiological class of inhibitory interneurones is described which, when stimulated by intracellular current passage, evoke short-latency, probably monosynaptic, strychnine-sensitive inhibitory potentials in contralateral motoneurones. These inhibitory interneurones fire once per swimming cycle in phase with the ipsilateral motor root discharge. They therefore have a pattern of activity which would cause them to inhibit motoneurones of the antagonistic motor centre at an appropriate part of the swimming cycle. The intracellular injection of horseradish peroxidase (HRP) has allowed the morphology of these inhibitory interneurones to be characterized. They have unipolar cell bodies with a thick proximal process with short dendrites which crosses the spinal cord ventrally and then bifurcates with one axonal branch ascending into the hind brain and the other descending the spinal cord. These anatomical features are typical of the 'commissural interneurones' first described by Roberts & Clarke (1982). There are also some inhibitory interneurones which can inhibit motoneurones on the same side of the spinal cord. At least some of these interneurones may be commissural interneurones with ipsilateral axons and they may play a role in the generation of the swimming rhythm. PMID- 4020708 TI - [Close interdependence between passive and active soleus muscle torques in man: approach to the coregulation of the number of sarcomeres and length of the connective tissue]. AB - Soleus muscle has, to as great an extent as possible, been functionally isolated in man. A device previously described permitted measurement of the soleus torque as a function of the tibia-calcaneum angle, and not as a function of tibia-foot angle. This latter angle cannot be correctly related to soleus length, since the arch of the foot can not be considered as rigid throughout the experiment. Ankle movements were performed on a horizontal plane by successive increments of 5 degrees from full extension (plantar flexion) up to full flexion (dorsiflexion). Passive torques were measured for every angle. At the same angles, the total torques were recorded while the subject exerted a voluntary constant contraction which corresponded to 45% of the maximum integrated electromyographical activity of soleus muscle. The active torque-angle curve was obtained by subtracting, for the same angle, the passive from the total torques. It must be stressed that, when the muscle is maximally shortened, little or no torque was measured. For the angle corresponding to the top of the sub-maximal active curve (integrated electromyographic activity 45% of the maximum), the passive torque was about 1.75 Nm and showed no significant interindividual variations. This result contrasted with the marked interindividual shifts which affect both passive and active curves. This interdependence of passive and active curves in human soleus muscle is compatible with the results of a previous study in the cat showing the concomitant adaptations of sarcomere number and connective tissue length. PMID- 4020707 TI - Regulation of cytosolic calcium concentration in presynaptic nerve endings isolated from rat brain. AB - The regulation of cytosolic Ca concentration ([Ca]i) was studied with the fluorescent Ca indicator, quin2, in pinched-off presynaptic nerve endings (synaptosomes) isolated from rat brain. The resting [Ca]i is 0.1-0.2 microM, in solutions containing 1-2 mM-Ca. [Ca]i increases by only 100-150 nM when the external Ca concentration is increased from 0.02 to 2 mM. The mitochondrial inhibitors valinomycin and fluoro-carbonyl cyanide phenylhydrazone (FCCP) increase [Ca]i by 100-200 nM. This increase is not correlated with the resting level of [Ca]i prior to the addition of inhibitors, but it is dependent on the presence of external Ca. It seems likely that the effect of these inhibitors on [Ca]i is a secondary consequence of metabolic inhibition. [Ca]i increases by about 2-fold when the external Na concentration is lowered from 145 to 5 mM, and returns to its initial level when external Na is restored. This recovery occurs also in the presence of FCCP. These results suggest that Na/Ca exchange, but not mitochondrial Ca uptake, plays a role in regulating [Ca]i and in allowing the nerve terminals to recover from Ca loading. PMID- 4020709 TI - [An anesthetic technic in dogs for studying the arrhythmogenic effects of acute coronary occlusion]. AB - Intramuscular injection of levomepromazine (0.5 mg/kg) 30 min before intravenous injection of 10 mg/kg pentobarbital sodium induces a good surgical anaesthesia in dogs artificially ventilated with 50% N2O and 50% O2 and given 0.01 mg/kg atropine and 0.1 mg/kg pancuronium intravenously before left thoracotomy. This protocol is suitable for the study of the arrhythmogenic effects of acute one stage coronary artery ligation in anaesthetized dogs. In fact, minor interference with the autonomic nervous system appears to be involved since heart rate is maintained slow and mean aortic pressure is kept within normal limits, as pH, PaO2, anc PaCO2 during subsequent periods. Acute circumflex coronary arterio venous pedicle ligation close to the left main trunk division resulted in this model in a high incidence of ventricular fibrillation (10 out of 15 dogs) early (7 +/- 4 min) after occlusion. Specific interventions aimed at reducing the incidence of early post-ischemic life-threatening ventricular arrhythmias might be tested in this model. PMID- 4020710 TI - [Relation between maximal oxygen consumption and the record time in the 1500 meter run. Analysis of Lloyd's model]. AB - Lloyd's equation (Lloyd, 1967 b) has been applied to the calculation of record time in the 1 500 meters foot race from VO2 max. Twenty-eight healthy male subjects participated in this investigation. Record times decrease with increasing VO2 max. The theoretical curve plotted from Lloyd's equation is consistent with this trend. Moreover, the relationship between calculated record times (TRc) and measured record times (TRm) is highly significant (TRc = 74.3 + 0.7 TRm; r = 0.883; P less than 0.001). These results validate Lloyd's equation and hypothesis. PMID- 4020711 TI - [Epileptogenesis caused by the kindling effect in diving at 3 ATA of air]. AB - The kindling effect is an experimental model of epilepsy which results from an intermittent application of focal electrical stimulations to certain regions of the brain. Generalized seizures are usually obtained after about fifteen stimulations of amygdala in the rat. We studied the kindling effect in hyperbaric hyperoxic conditions. Eleven Wistar rats were stimulated daily in a caisson and all stimulations were delivered after 30 min of diving at 3 ATA of air. Diving inhibited kindling in half animals. In the others, which all presented generalised convulsions, diving produced a reduction in seizure duration, especially during the generalisation phase. PMID- 4020712 TI - Effects of cold exposure on calcitonin secretion in the young rat. AB - The effects of cold exposure on calcitonin (CT) secretion were evaluated in young rats. Acute cold exposure (5 h to 5 degrees C) induced a rise in plasma CT concentrations and a decrease in thyroidal CT stores without change in total and ionized plasma calcium levels. The cold activation of sympathico-adrenomedullary axis and the inhibition of CT response to cold after beta-antagonist treatment might suggest that endogenous catecholamines can enhance CT secretion in young rats. Cold adaptation (3 weeks to 5 degrees C) induced a fall in plasma calcium concentration and a rise in thyroidal CT stores without change in plasma CT levels. The high plasma glucocorticoid levels which are known to occur during chronic cold exposure could be involved in the rise of thyroidal CT content in cold adapted rats. PMID- 4020713 TI - Calcemic responses of Varanus flavescens to prolactin administration. AB - The daily intraperitoneal injections of ovine prolactin to Varanus flavescens (10 I.U./0.2 ml/100 g body wt for 7 days) induced a rise in serum calcium which persisted until the end of the experiment. PMID- 4020714 TI - [Characteristics of esophageal antiperistaltic activity in sheep]. AB - Oesophageal motility was investigated in standing conscious sheep. A manometric method was used in four animals; two sheep, fitted with permanent electrodes at four levels, were used for oesophageal electromyography. The occurrence of retrograde peristalsis (mean speed 71,5 cm.s-1) at the beginning of every rumination cycle is reasserted. The characteristics of this activity are pointed out, with reference to normal peristalsis during the deglutition of saliva. Different types of stimulation have been compared. Retrograde peristalsis (mean speed 66 cm.s-1) can be triggered readily in non-ruminating animals by the association of two stimulations. One being oesophageal distension and the other injection of a solution prepared with some physical or chemical components of the rumen liquid. No specialized sensitive area could be demonstrated. However, facilitation is evident during reticular contractions. Retrograde waves of contraction always start from the terminal part of the thoracic oesophagus, whatever the level of stimulation. PMID- 4020715 TI - [Time-dependent measurement of differential digital plethysmogram in bicycle ergometer exercise]. AB - Time-dependent measurements of differential digital plethysmogram during exercise were made on five male subjects. The results obtained were as follows; Differential digital plethysmogram (delta DPG) was obtained by using biophysical amplifier with the time constant of 0.03 seconds which minimized the fluctuation of the baseline in digital plethysmogram (DPG). A linear relationship was shown in P wave amplitude of both delta DPG and DPG. The decrease in delta DPG-P waves was observed in visual concentrations, mental learning and arithmetic, initial inspiratory phase with tachycardia, maximal inspiratory and/or expiratory breath holding, and head-up tilt at 60 degrees or over. The increase in delta DPG-P waves was obtained at the expiratory phase with bradycardia and in the effect of alcohol intake. During 15 minutes of bicycle ergometer exercise at 750 kpm/min, the P wave amplitude in delta DPG decreased to 77% of the control in the first one minute of exercise, and then gradually increased to 218% at the final stage of exercise (p less than 0.01). Heart rate measured simultaneously increased, as compared from the beginning of exercise. P wave amplitude and heart rate after exercise decreased progressively to the control level. It is suggested that the initial decrease in P wave amplitude of delta DPG couples with the dominant activity of the sympathetic vasoconstrictor, and the final increase in P waves is due to the compound factors of the increased cardiac output and arteriolar vasodilation. PMID- 4020716 TI - Acute pancreatitis in north and north-east Scotland. PMID- 4020717 TI - Endoscopic papillotomy for removal of common bile duct stones without cholecystectomy. PMID- 4020718 TI - Cholecystectomy, cholelithiasis and colorectal carcinoma. PMID- 4020719 TI - Prophylactic metronidazole with and without cefuroxime in elective colorectal surgery. A prospective randomised double-blind study. PMID- 4020720 TI - Giant monostotic fibrous dysplasia of the jaws. PMID- 4020721 TI - Retroperitoneal teratoma with rupture into the left lung. PMID- 4020722 TI - Impalement of the chest by a reinforced steel rod. PMID- 4020723 TI - Multiple perineal fistulas and bladder carcinoma. PMID- 4020724 TI - Adhesions as a primary cause of massive intraperitoneal bleeding. PMID- 4020725 TI - Perineal healing after panproctocolectomy for inflammatory bowel disease. PMID- 4020726 TI - Management of severe head injuries in a non-neurosurgical trauma centre. PMID- 4020727 TI - Osteochondral fractures of the patella. A method of fixation. PMID- 4020728 TI - Patient comfort after upper abdominal surgery. Effect of routine nasogastric suction. PMID- 4020730 TI - A study of the food eaten in conventional Royal Navy submarines. PMID- 4020729 TI - The Telfer osteotomy for hallux valgus. PMID- 4020731 TI - Training for the role of staff nurse--professional and personal preparation of recently qualified Registered General Nurses in the QARNNS. PMID- 4020732 TI - Training in occupational medicine in the Royal Navy--a personal view. PMID- 4020733 TI - [Noninvasive diagnosis of patellar chondromalacia]. AB - The present paper investigates into plain film appearance of chondromalacia patellae verified with the aid of operative and arthroscopic inspection. Roentgenograms taken according to the defile-technique were obtained from 86 patients prior to the operation and at post operative intervals to give a two year follow up. It can be drawn from the results that the incidence of radiologically detectable type I lesions is in the range of about 60%, whereas the diagnostic sensitivity for type III lesions have been determined to reach 100%. While significant improvement of all clinical symptoms could be observed during the postoperative period, patellar roentgen morphology proved to be almost entirely unchanged. Therefore it may speculated that severe chondromalacia patellae is likely to represent an early sign of patellar osteoarthritis. PMID- 4020734 TI - [Radiologic imaging of annulo-ectasia disease of the aorta. Experience with 26 cases]. AB - The authors describe the radiologic appearance of annulo-aortic ectasia in 26 patients who had plain chest radiography and aorto-seriography. Two also underwent C.T. Aortography is the most performing method to appreciate the extent of aortic ectasia, the perturbations of the aortic root and to diagnose acute or chronic dissections. Aortography remains a most valuable complement of echocardiography for preoperative staging. PMID- 4020735 TI - [Primary neuroblastoma. A new form of median line cerebral calcification]. AB - Based on a series of 7 cases the original characteristics of neuroblastomas are described, these tumors being of neuronal origin and exhibiting such constant calcifications and median line sites that they can be evoked in spite of their rareness. PMID- 4020736 TI - [X-ray computed tomographic aspects of gelatinous disease of the peritoneum. Apropos of 5 cases]. AB - Gelatinous disease of the peritoneum, designated by Anglo-Saxon authors as peritoneal pseudomyxoma is a rare affection characterized by the presence in the peritoneal cavity of a mucoid substance corresponding to an acid mucopolysaccharide. It develops secondary to an acid mucopolysaccharide. It develops secondary to mucosecreting malignant tumors, particularly of ovarian or appendicular origin, and its capacity to provoke multiple recurrences makes it of fairly poor prognosis. Diagnosis has been improved by the availability of non aggressive investigations such as ultrasound and particularly computed tomography imaging. Suggestive CT scan signs are hepatic scalloping and a partitioned intraperitoneal effusion. Follow up scans can give data on the course of the disease and detect any complications (renal and digestive lesions, intraperitoneal abscess). PMID- 4020737 TI - [Microcomputer simulation of nuclear magnetic resonance imaging contrasts]. AB - The high information content of magnetic resonance images is due to the multiplicity of its parameters. However, this advantage introduces a difficulty in the interpretation of the contrast: an image is strongly modified according to the visualised parameters. The author proposes a micro-computer simulation program. After recalling the main intrinsic and extrinsic parameters, he shows how the program works and its interest as a pedagogic tool and as an aid for contrast optimisation of images as a function of the suspected pathology. PMID- 4020738 TI - [Spondylodiscitis after embolization of an extramedullary intraspinal arteriovenous fistula]. AB - The authors report a case of spondylitis Th11-Th12 occurred 1 month after embolization of an intraspinal extramedullary arteriovenous fistulae; this fistulae was fed by 11th left intercostal artery. The infecting organism isolated from the affected intervertebral disc was streptococcus sanguis a common agent of dental abscess. PMID- 4020739 TI - [Unusual late disclosure of left congenital diaphragmatic hernia]. AB - A posterolateral hernia through Bochdalek foramina was discovered in a 27 months old child under unusual circumstances. During lifting an heavy weight, migration occurred of the abdominal content through the foramina into the left thorax. The size of the pleuroperitoneal communication was well demonstrated by peritoneography. Possible rupture of a diaphragmatic relaxation was eliminated on findings at surgery. Reconstructive surgery led to an uneventful recovery which is the rule in this type of late-discovered hernia. PMID- 4020740 TI - [A system for improving the quality of the image in knee arthrography]. AB - A simple and inexpensive technique for arthrography is described. A standard fluoroscopic unit with overhead tube is used. A special cassette holder allows the use of cassettes with a screen-film combination normally used for mammography. An exceptionally good combination of factors important for a good image quality is obtained. PMID- 4020741 TI - [National survey on radiodiagnosis. Comparative analysis of the activity of different sectors (3)]. AB - The survey has estimated the global annual production of radiological procedures in France (1982) at 45,4 millions. The large public hospitals (including University hospitals) produce up to 42% of the total; the mean number of annual procedures by X-Ray unit being 4 000, in this sector. The private sector (including clinics and offices) has a production ratio between 2 350 and 2 800 annual procedures by X-Ray Unit; some type of examinations are over represented as compared with the public sector for example lumbar and dorsal spine and digestive. Specialized procedures such as vascular and neuro-radiological represent a quasi monopoly of the public sector. In term of economic behavior, some differences appear between the public and private sectors in the way to account for the procedures to the Social Security System. These are partly due to differences in the complexity of the procedures (for example in the case of abdomen, stomach and upper G.I., the latter being more often performed in hospitals) and to different medical practices (number of films; utilisation of divided films, etc.). The share of procedures executed under the responsibility of a radiologist yields 88% of the total. PMID- 4020742 TI - Cervical screening. PMID- 4020743 TI - Antibiotics, sore throats and rheumatic fever. AB - From a retrospective study of hospital records, it is calculated that the present incidence of rheumatic fever in Scottish children is 0.6 per 100 000 per year. This is in keeping with recent research from other developed communities. An attempt is made to assess the relative risk of developing rheumatic fever after antibiotic-treated streptococcal sore throats and non-antibiotic-treated streptococcal sore throats. The risk in both cases is low (probably in the order of 1:30 000) and there is no evidence that prescribing antibiotics for prodromal sore throats confers benefit. PMID- 4020744 TI - How patients manage asthma. AB - In this paper we discuss how patients cope with asthma and suggest that individuals use medical advice selectively in a manner they consider appropriate to their personal and social circumstances. Use of medical services is influenced by patients' perception of the effectiveness of medical therapies, concern about the long-term use of drugs, access to alternative therapies, support and advice from others and the need to make particular sense of living with a chronic disease. Some people are reluctant to use medical services under any circumstances. PMID- 4020745 TI - What does a trainee see? AB - The experience of a trainee was documented in detail for a complete training year and the data were stored and analysed using a suite of purpose-written computer programs. The results indicate that the experience of the trainee was extremely similar to that of the trainer and that continuity of care must be considered in planning a training programme. The findings also emphasize that general practice deals with a wide range of problems many of which occur infrequently and therefore may not be adequately covered during the training year. PMID- 4020746 TI - Audit of abdominal pain in general practice. AB - An audit of 150 consecutive cases of abdominal pain presenting to an urban teaching practice between October 1983 and May 1984 was performed. The median duration of pain prior to presentation was two days. Females predominated in all age groups.Eighty-nine per cent of these patients were managed entirely in the practice and of these, 52 per cent were managed with reassurance and advice alone, while 48 per cent also received a prescription. Only 15 per cent of patients were investigated in any way by the practice. Of the 17 patients (11 per cent) referred, nine were referred as emergencies and eight were admitted that day. However, there were only three true surgical emergencies in the entire series (one appendicitis, one intussusception and one fulminating pancreatitis). PMID- 4020747 TI - An evaluation of the effectiveness of individual and group cognitive therapy in the treatment of depressed patients in an inner city health centre. AB - Depressed patients were allocated randomly to individual cognitive therapy, group cognitive therapy or a waiting list ;treatment as usual' control group. Blind clinical and psychometric assessment of patients revealed that those who underwent cognitive therapy did significantly better than those on the waiting list. There was no significant difference between patients treated with group or individual cognitive therapy. Threatment gains were maintained at follow-up at 12 months. Prognostic characteristics for the selection of depressed patients for cognitive therapy on the basis of the chronicity and social stresses are identified. It is concluded that cognitive therapy is an effective treatment which can be applied cost-effectively in general practice. PMID- 4020748 TI - Audit of screening for hypertension in general practice. AB - An audit of a practice which has a policy of opportunistic screening for raised blood pressure showed that 80 per cent of patients born between 1930-44 had been screened in the last five years. Patients who had not been screened were identified and contacted; this increased the percentage screened to 87 per cent. Only four possible new hypertensives were identified. It is suggested that the effort and expense of achieving this result was not worthwhile and that opportunistic screening is the cheapest and easiest method of screening for high blood pressure. PMID- 4020749 TI - The elderly as underconsulters: a critical reappraisal. AB - This paper reconsiders the evidence for underconsultation among the elderly. Earlier evidence from studies of unreported illness is reassessed and new data are presented for the ratio of self-reported illness to number of consultations. It is concluded that underconsultation among the elderly is exaggerated and that there are implications for screening and case-finding. It is suggested that attention should be directed towards a combination of self-referral and multi tiered screening for low contact and high risk groups. PMID- 4020750 TI - Medicine and the media. PMID- 4020751 TI - Laughter and medicine. PMID- 4020752 TI - Treating insomnia. PMID- 4020753 TI - Clinical diagnosis of gall-bladder disease. AB - An investigation into the diagnosis of gall-bladder disease in general practice by simple clinical methods was carried out over seven years; 916 patients were seen in 1018 episodes of illness. These patients were examined particularly for oedema in the skin and subcutaneous tissue of the right hypochondrium, Murphy's sign, clinical jaundice and bilirubinuria.Oedema was found in 89% of the episodes of confirmed gall-bladder disease and in 74% of the suspected cases, but in only 4% of the other abdominal and thoracic conditions studied. Clinical jaundice or bilirubinuria or both occurred in 28% of the confirmed episodes of gall-bladder disease and in 12% of the suspected ones.If oedema, Murphy's sign and jaundice were all present there was a 72% probability of the condition being gall-bladder disease.During the study, there was a 45% increase in the number of new cases of gall-bladder disease correctly diagnosed each year compared with the previous three and a half years, and an 89% decrease in the number of cases missed. PMID- 4020754 TI - Comparative rating of consultation performance: a preliminary study and proposal for collaborative research. AB - Factors governing the appropriateness, reliability and validity of rating scales in the measurement of professional performance are reviewed. The origin and preliminary testing among undergraduated and general practitioners of a brief consultation rating schedule is described.Statistical criteria are proposed for the analysis of ratings, by groups, in the comparison of consultation performance. Using these criteria the capacity of the 10 rating schedule items to discriminate between two contrasting consultations was examined. Each of the items was used at some time by students or doctors to express significant preference for the same consultation; and on this basis all the items are considered to merit inclusion. One item showed highly significant intra- and inter-observer reliability.The schedule is reproduced in full, together with a data-collection document and significance chart, with the aim of encouraging groups of doctors to test the validity of the items in the comparison of other pairs of consultations. It is proposed that future versions of the schedule should reflect the experience of such groups in testing existing items and in defining additional items which satisfy the proposed criteria. PMID- 4020755 TI - Consumer-oriented groups: a new approach to interdisciplinary teaching. AB - Difficulties in the development of primary health care teams have been demonstrated by a number of authors. The important place of interdisciplinary teaching in this development had been stressed. This paper describes an experimental series in which emphasis has been placed on the patient's view of the input of different team members. The value of this approach is discussed. PMID- 4020756 TI - Accessing remote data bases using microcomputers. AB - General practitioners' access to remote data bases using microcomputers is increasing, making even the most obscure information readily available. Some of the systems available to general practitioners in the UK are described and the methods of access are outlined. General practitioners should be aware of the advances in technology; data bases are increasing in size, the cost of access is falling and their use is becoming easier. PMID- 4020757 TI - Food propagandists--the new puritans. PMID- 4020758 TI - Place of birth and perinatal mortality. AB - Analyses of the published results of national surveys and specific studies, as well as of the official stillbirth statistics, consistently point to the conclusion that perinatal mortality is significantly higher in consultant obstetric hospitals than in general practitioner maternity units or at home, even after allowance has been made for the greater proportion of births in hospital at high pre-delivery risk. Unpubliched results of the British births 1970 survey, which have now become available, make possible a direct and authoritative analysis of data on the safest place of birth. Not only does this make the earlier conclusion more certain, but it confounds the doctrine that obstetric intranatal care is particularly beneficial for high pre-delivery risk births. There is no evidence from recent years that the findings of 1970 are not equally valid in the 1980s. PMID- 4020759 TI - Wide variations in the night visiting rate. AB - The night visit record of an out-of-hours rota service of a large health centre which includes 10 group practices was examined. The mean annual night visiting rate for the health centre was 35.2 per 1000 patients, ranging from 25.8 to 43.5 between individual practices. The organization of medical care at night was the same for all the practices, and no major demographic differences between practices were identified. It is argued that the doctor-patient relationship may have an influence on differences in night visiting rates. PMID- 4020760 TI - Hyperthermia following a sauna bath. PMID- 4020761 TI - Inhibition of non-genomic responses to oestrogen in the rat uterus by testosterone propionate. AB - Testosterone propionate (50 mg/kg), administered together with oestradiol, inhibited the oestrogen-induced uterine eosinophilia, deep endometrial oedema and the increase in uterine wet weight, 6 h after treatment. The same dose of the androgen decreased the number of eosinophils in the blood and increased their degranulation, explaining the effect of testosterone in the uterus. The high doses of the androgen used were in the range of the doses reported by others to block selectively the oestrogen-induced increase in uterine peroxidase content but not other responses to oestrogen or the cytosolic oestrogen receptor translocation to the nucleus. The dissociation by high doses of testosterone of the oestrogen-induced uterine eosinophilia, wet weight increase and oedema from other responses to oestrogen in the absence of any measurable effect of testosterone upon cytosolic-nuclear oestrogen receptors supports the idea that uterine eosinophilia and oedema are oestrogenic responses regulated by mechanisms different from those of the genomic responses, and is in agreement with the hypothesis of the mediation of uterine oedema by eosinophils. PMID- 4020763 TI - Photoelectron imaging of guinea-pig, hamster and human spermatozoa. AB - Photoelectron images of mammalian spermatozoa were obtained by subjecting the specimens to u.v.-irradiation and focussing the emitted electrons by electron optics (photoelectron microscopy). Guinea-pig, hamster and human spermatozoa were fixed in glutaraldehyde, deposited on conductive glass discs, and dehydrated. Sufficient quantities of photoelectrons were released from the surface of spermatozoa to produce images without staining, coating or metal shadowing. The large planar heads of guinea-pig spermatozoa were easily resolved with good delineation of acrosomal and postacrosomal regions. Residual vesicles could be visualized on the surface of the inner acrosomal membrane of spermatozoa that had undergone the acrosome reaction. Also detectable in these photoelectron images were finer membrane surface details, periodicities in the midpiece region of the tail which coincided with the distribution of mitochondria, and periodicities in the principal piece which appeared to be related to fibrous sheath components. Hamster spermatozoa were similarly well resolved but human spermatozoa were more difficult to image because of their increased surface curvature. The mechanism responsible for detection of these surface details is primarily topographical contrast rather than material contrast, since spermatozoa coated with a thin layer of gold or platinum exhibited similar features, although at reduced resolution, as the uncoated specimens. PMID- 4020762 TI - Follicular atresia in relation to oocyte morphology in non-pregnant and pregnant women. AB - Antral follicles from normally menstruating women and women in the third trimester of pregnancy were classified as healthy or atretic by flow cytometric DNA measurements on aspirated granulosa cells and by the concentration of steroids in the follicular fluid. The oocytes contained in these follicles were characterized as healthy or degenerating by their morphology at the light microscopic level. In 98% of the cases (61/62) morphologically healthy or degenerating oocytes were found in follicles which were classified as healthy or atretic respectively. In the normally menstruating women degenerative changes in the oocyte and the remainder of the follicle appeared to occur in synchrony. In pregnant women asynchrony was noted between the oocyte and the remainder of the follicle as follicular atresia progressed. The present study demonstrated the usefulness of flow cytometric DNA measurement in characterizing antral follicles of all sizes as healthy or more or less atretic. PMID- 4020764 TI - Luminal secretion of myo-inositol by the rat epididymis perfused in vitro. AB - A technique for perfusing the lumen of rat epididymal tubules maintained in vitro showed that [3H]inulin was largely excluded from the lumen of unravelled tubules from the cauda and tubules from the corpus if the connective tissue capsule was removed. The preparation transported [3H]inositol from the bath fluid for 3 h against a concentration gradient in both regions with activity rising (16-29% of bath fluid values) in the cauda and reaching a plateau (18%) in the corpus epididymidis. HPLC showed that radioactivity was solely associated with inositol and its movement to the lumen was reduced by raising inositol in the bath fluid from 50 microM (plasma levels) to 10 mM, but not affected by reducing the glucose concentration in the bath fluid or introducing physiological concentrations of inositol (30 mM) into the lumen. Secretion into the caudal lumen of unlabelled inositol measured by g.l.c. was maintained for 3 h at concentrations (300 microM) greater than those in the bath fluid and was not reduced when glucose or inositol were removed from the bath. In contrast, glucose was only detectable in the lumen when it was present in the bathing medium, reaching 1% of this concentration. Radioactivity appeared in the epididymal lumen reaching a plateau (19% of bath fluid values) in the corpus and cauda when [3H]glucose was added to the bath fluid, but no radiolabelled inositol was found in the lumen. We conclude that epididymal tissue is a major source of secreted inositol. PMID- 4020765 TI - Production of (S)-3-chlorolactaldehyde from (S)-alpha-chlorohydrin by boar spermatozoa and the inhibition of glyceraldehyde 3-phosphate dehydrogenase in vitro. AB - The (S)-isomer of the male antifertility agent alpha-chlorohydrin was metabolized by mature boar spermatozoa in vitro to (S)-3-chlorolactaldehyde. This oxidative process, which did not occur when (R)-alpha-chlorohydrin was offered as a substrate, was catalysed by an NADP+-dependent dehydrogenase that converts glycerol to glyceraldehyde. (S)-3-chlorolactaldehyde, produced by this metabolic reaction or when added to suspensions of boar spermatozoa, was a specific inhibitor of glyceraldehyde 3-phosphate dehydrogenase as assessed by the accumulation of fructose 1,6-bisphosphate and the triosephosphates. When glycerol and (S)-alpha-chlorohydrin were added concomitantly to boar spermatozoa in vitro, the presence of glycerol decreased the degree of inhibition of glyceraldehyde 3 phosphate dehydrogenase. Extracts of glyceraldehyde 3-phosphate dehydrogenase that were obtained from boar spermatozoa incubated with (S)-alpha-chlorohydrin or (R,S)-3-chlorolactaldehyde showed significant reductions in their enzymic activity. PMID- 4020766 TI - Seasonal and circadian patterns of circulating prolactin during lactation and seasonal quiescence in the tammar, Macropus eugenii. AB - Prolactin was measured in peripheral plasma of female tammars once a week for 14 months and every 2 months it was measured in a subgroup of 7 tammars at hourly intervals for 28 h to determine short-term changes in concentration. During the course of the study 6 females gave birth in January/February and reared their young to weaning in October-November, while another 4 gave birth 1.5-3.0 months later and weaned their young in November-December. Concentrations of prolactin were less than 40 ng/ml in a non-lactating animal and for the first 140 days of lactation in the others. Between 140 and 180 days of lactation the concentrations of prolactin fluctuated between 10 and greater than 100 ng/ml and thereafter remained high until the young vacated the pouch for the last time at about 250 days. After pouch exit the concentrations declined to about 40 ng/ml even though lactation continued for a further 21-35 days. Although the short-term patterns of prolactin concentrations showed no consistent relationship between light-dark phases there was an increase in the magnitude and duration of peaks of plasma prolactin which correlated with the stage of lactation. Removal of pouch young aged between 203 and 242 days for 24 h resulted in a rapid decrease in plasma prolactin concentration which was reversed when the young was returned to the pouch, indicating that the high levels of prolactin in the second half of lactation may be maintained by the sucking stimulus of the pouch young. This period of lactation, therefore, may be equated with lactation in eutherians, but there appears to be no eutherian equivalent to early lactation in the tammar. PMID- 4020767 TI - Cytogenetic and blood group studies of sheep/goat chimaeras. AB - Aggregation chimaeras were composed of quarter (or 1 cell) contributions from 4 cell blastocysts of sheep or goats, or of an 8-cell blastocyst of one species enveloped in three 8-cell blastocysts of the other. Gestation was in sheep or goat recipient females. Of the 10 living animals born, 3 were identified as interspecific chimaeras by body conformation and coat type among the 7 quarter/quarter aggregations and 1 among the 3 giant aggregates. Interspecific chimaerism was identified by cytogenetic study of umbilicus and blood lymphocytes respectively of 2 of these, one from each type of aggregate. Intraspecific sex chimaerism was found in 3 other animals; 2 were of giant aggregate origin, but the 1 of quarter/quarter origin must have acquired it by placental anastomosis with a twin conceptus. Tests using species-specific monoclonal antibodies and electrophoretic separation of haemoglobins and isoenzymes demonstrated sheep and goat erythrocytes in one giant aggregate chimaera; their relative proportions and those of the blood lymphocytes changed over a period of 31 months from approximately 60% goat and 40% sheep to more than 90% sheep. The plasma transferrins and amylases did not show similar relative changes from their predominantly goat-like character and, by implication, neither did their tissues of origin. PMID- 4020768 TI - Intratesticular distribution of testosterone in rats and the relationship to the concentrations of a peptide that stimulates testosterone secretion. AB - Methods have been established and validated for quantitative assessment of the distribution of testosterone in the testis, by measurement of testosterone concentrations in whole testis, in isolated seminiferous tubules and in testicular interstitial fluid. These measurements were made in individual rats injected 2-40 h previously with saline (0.9% NaCl) or a potent antiserum to ovine LH. Testosterone concentrations in interstitial fluid and seminiferous tubules were closely correlated (r = +0.98; n = 60) and their relationship was log linear over a 200-fold range. However, although the concentrations of testosterone in interstitial fluid and seminiferous tubules decreased progressively with time after LH antiserum injection, this decrease was far more pronounced for interstitial fluid. In association with this change there was a significant increase in the amounts of a locally-produced factor in interstitial fluid which stimulates basal and hCG-stimulated testosterone production by isolated purified Leydig cells. This increase was reversed by injection of hCG but not by peripheral injection of a dose (20 mg) of testosterone propionate which restored normal intratesticular concentrations of testosterone. It is concluded that the tubular 'conservation' of testosterone, which occurs as interstitial fluid levels of this steroid decrease, may be a consequence of restricted diffusion of testosterone out of the tubules, but is also associated with increased amounts of a peptide stimulator of testosterone production. PMID- 4020769 TI - Acquisition of sperm motility and its maintenance during storage in the lizard, Lacerta vivipara. AB - Lizard spermatozoa, which are non-motile in the testis, develop the ability to swim as they pass along the excurrent duct. The addition of caffeine, a phosphodiesterase inhibitor, induced forward motility in spermatozoa from the caput epididymidis and increased the velocity of spermatozoa from the distal part of the epididymis. Caffeine had no effect on the motility of testicular spermatozoa. This suggests that sperm motility in this species is cyclic AMP dependent but this factor alone is not sufficient to induce testicular sperm motility. In samples from the distal region of the epididymis, sperm motility was maximal in April just after the breeding season and then decreased significantly during the following months. A parallel can be drawn between these data and the levels of testosterone in the plasma. In the lizard, as in mammals, the epididymis may play an important role in the maturation of spermatozoa. PMID- 4020770 TI - Qualitative and quantitative structural changes during pig oocyte maturation. AB - Pig oocytes were examined at hourly intervals after stimulation with hCG. Meiosis was resumed between 20 and 30 h after hCG. This coincided with a decline in the number of mitochondria and evidence is presented which indicates that this was due to fusion. The number of lipid droplets increased and the volume fraction of large vesicles decreased. Both these organelles maintained a close spatial relationship with the endoplasmic reticulum (ER). Mitochondria were clustered at the periphery of the cell before hCG injection but dispersed with maturation. The volume occupied by large vesicles, 'protein bodies' and Golgi also decreased at the edge of the oocyte with the progression of maturation. PMID- 4020771 TI - Effect of intravaginal implants of melatonin on the onset of ovarian activity in adult and prepubertal ewes. AB - Melatonin was administered intravaginally in Silastic tubing to adult and prepubertal ewes. In Exp. 1, ewe lambs (born early March) were given intravaginal melatonin implants at a mean age (+/- s.e.m.) of 7.5 +/- 0.1 weeks (Group E, N = 10) or 19.4 +/- 0.2 weeks (Group L, N = 10). The third group (Group C, N = 10) received empty implants. In Exp. 2 mature ewes were given implants on 13 May (Group E, N = 10) or 18 July (Group L, N = 10) or received empty implants (Group C, N = 10) on one of these two dates. Blood samples were taken twice weekly for progesterone assay. In Exp. 1 the mean age (+/- s.e.m.) at puberty (progesterone greater than 2 nmol/l for two consecutive samples) was 35.4 +/- 0.8 weeks. Puberty was advanced by 5.2 weeks in Group L lambs, occurring at a mean age of 30.2 +/- 0.7 weeks (P less than 0.001). In Group E lambs the timing of puberty was unaltered, occurring at a mean age of 34.8 +/- 0.6 weeks. Mature ewes in Group L (Exp. 2) showed increased incidence of ovarian activity (9/10 ewes cycling by 26 September) compared with the control ewes (1/10) (P less than 0.001), but there was no effect in Group E ewes (3/10). The results demonstrate that continuous melatonin administration to adult and prepubertal ewes can mimic the effect of short days in terms of the reproductive response, and that the present and previous exposure to melatonin is critical in determining the response. PMID- 4020772 TI - Prospects and limitations of the rosette inhibition test to detect activity of early pregnancy factor in the pig. AB - After preincubation of lymphocytes in serum of non-pregnant pigs and using a standard anti-pig-lymphocyte serum the upper limit of the 99.9% confidence interval of rosette inhibition titres (RIT) for pig serum was calculated to be 11.4 and all titres greater than 12 were defined as a proof of early pregnancy factor (EPF)-activity. The reproducibility of the RITs with serum samples of pregnant pigs was considered satisfactory (interassay coefficient of variation 23.8%), whereas their reproducibility was considered good with sera taken from non-pregnant animals (interassay coefficient of variation 6.5%). Problems of the test were particularly evident due to the absence of increased RITs after previous incubation of lymphocytes in serum of pregnant pigs. Therefore, all EPF negative samples were reanalyzed up to two times; pregnancy was then correctly diagnosed for 88.7% of sows. There were 8.6% false positive results (N = 70) and 12.2% false negative results (N = 205). During the first half of pregnancy RITs displayed periodic fluctuations which resembled the physiological cycle interval of the pig. Between Weeks 5 and 9 of pregnancy greater numbers of EPF-negative sows were detected. Subsequently, a continuous increase of mean RITs occurred, which then declined gradually from Day 80 of pregnancy. Similar changes were observed for progesterone values in the dialysed serum samples. However, highest progesterone concentrations always followed elevated RITs with a delay of 1.5-4 days. A subthreshold cyclicity of ovarian and luteal function probably persists despite pregnancy. PMID- 4020773 TI - Detection of activity similar to that of early pregnancy factor after mating sows with a vasectomized boar. AB - Incubation of normal pig lymphocytes in serum samples collected from 10 sows immediately before, and at daily intervals after mating with a vasectomized boar significantly elevated the rosette inhibition titre (RIT) of a standard antilymphocyte serum in 6 animals on the first but not on the 2nd and 3rd day after copulation. Infusion of seminal plasma without mating into 5 sows induced an obvious, but not statistically significant, transient rise of titres in 3 pigs. Neither sodium chloride infusion (N = 5), nor sham copulation with diverted penis (N = 5) influenced serum RITs. Porcine seminal plasma showed an inherent rosette-inhibiting property. A depression of rosette formation was evident in a concentration-dependent fashion up to a dilution of 1 in 320. Similarly, preincubation of lymphocytes in serial dilutions of seminal plasma in a non pregnancy serum sample led to an amplification of the rosette inhibiting capacity of the antilymphocyte serum. Non-specific activation of the eggs to release a signal which induces the production of early pregnancy factor (EPF) or the resorption of seminal plasma components into the blood circulation are considered as possible explanations for the EPF-like activity after mating with a vasectomized boar. PMID- 4020774 TI - Effect of oestradiol-17 beta on ovarian and serum concentrations of relaxin during the second half of pregnancy in the rat. AB - Immunoactivity concentrations of ovarian relaxin, serum relaxin and serum progesterone were determined from Day 12 through Day 18 of pregnancy in rats treated with oil or oestradiol-17 beta after hysterectomy or hypophysectomy and hysterectomy on Day 12. Relaxin and progesterone concentrations increased between Days 12 and 18 in sham-operated rats but failed to increase or declined in oil treated hysterectomized or hypophysectomized-hysterectomized animals. Oestradiol treatment increased serum concentrations of relaxin and progesterone in hypophysectomized-hysterectomized rats on Day 15 and increased the concentrations of ovarian and serum relaxin and serum progesterone in hysterectomized rats on Day 18. These data are consistent with the concept that placental support for the promotion and maintenance of relaxin and progesterone concentrations from Day 12 through Day 18 may be mediated, at least in part, through a common mechanism(s) which involves oestradiol. PMID- 4020775 TI - Effects of nicotine on oviducal blood flow and embryo development in the rat. AB - Nicotine (5.0 mg/kg) was injected (s.c.) twice daily on Day 1 or Days 1-4 or 1-5 of pregnancy. Cumulative doses of nicotine retarded embryo cell cleavage and substantially reduced embryo cell number (saline vs nicotine: 42.5 +/- 1.7 vs 22.1 +/- 1.9 nuclei/embryo, at 12:00 h on Day 5; P less than 0.05). However, treatment for even 1 day (Day 1) significantly reduced cell number (saline vs nicotine: 42.5 +/- 1.7 vs 30.5 +/- 0.9, at 12:00 h day on Day 5; P less than 0.01). Nicotine injection also resulted in a marked and prolonged reduction in oviduct blood flow (pretreatment vs 90 min after nicotine: 0.61 +/- 0.06 vs 0.37 +/- 0.10 ml/min . g-1; P less than 0.005). The results indicate that, in the rat, even a brief exposure to nicotine, the chief alkaloid of tobacco, reduces oviducal blood flow and the rate of embryo cell proliferation. The embryo is therefore susceptible to the effects of nicotine before implantation. PMID- 4020776 TI - Intraluminally injected oil induces changes in vascular permeability in the 'sensitized' and 'non-sensitized' uterus of the mouse. AB - After suitable sensitization of ovariectomized mice with progesterone and oestradiol, the intrauterine instillation of oil produces a massive decidual cell reaction. Vascular permeability, as reflected by the extra-vascular accumulation of 125I-labelled human serum albumin, increased after oil instillation and was maintained at 2-3 times control values for at least the next 3 days. Although oil instillation did not produce a decidual response in females treated with progesterone alone, an increase in vascular permeability (about 2 times control levels) still occurred. This response peaked 8 h after oil instillation and was not maintained. These results indicate that the progesterone-dominated uterus which has not been sensitized with oestradiol cannot be viewed as completely unresponsive to the stimulus of oil and demonstrate that a marked increase in vascular permeability is not itself sufficient to induce decidualization of progesterone-dominated uterine stromal cells. The uterine extravascular accumulation of 125I-labelled albumin was increased both in association with tribromoethanol anaesthesia and after oestradiol treatment of progesterone-primed animals. In pregnant mice, the appearance of Pontamine Sky Blue spots provided an earlier indication of implantation than did determination of total uterine extravascular 125I-labelled albumin accumulation. PMID- 4020777 TI - Production and characterization of monoclonal antibodies to cross-reactive antigens of human and porcine zonae pellucidae. AB - Three monoclonal antibodies (Mabs), 3A4-2G1, 1D5-2B7 and 1F2-1B8 were produced against heat-solubilized porcine zona pellucida (ZP). Each Mab stained intact ZP but no other pig tissues using immunofluorescence staining. All three Mabs stained selectively zonae pellucidae (ZPe) from pigs and humans but not from hamsters, rats or mice, and showed no inhibitory effect on sperm binding to human oocytes. When goat antiserum to mouse gamma-globulin was added to human oocytes pre-treated with 3A4-2G1 or 1D5-2B7, sperm binding to oocytes was completely blocked with formation of immune precipitates around them. SDS-PAGE analysis of the immune precipitates of 125I-labeled porcine zona proteins and Mab showed that the antigen binding 3A4-2G1 was mainly composed of components with approximate molecular weights of 92,000, 65,000 and 23,000 and the antigen binding 1D5-2B7 contained two components with approximate molecular weights of 57,000 and 49,000, respectively. The epitope of ZP antigen, corresponding to 3A4-2G1, was found to be present in the molecule of 92,000 daltons as demonstrated by enzyme immunostaining of the proteins after blotting to nitrocellulose membrane from SDS PAGE gels. PMID- 4020778 TI - Differential effect of human chorionic gonadotrophin on lymphocyte proliferation induced by mitogens. AB - Human chorionic gonadotrophin (hCG) inhibits the lymphoproliferative responses of human peripheral blood mononuclear cells (PBM) to phytohaemagglutinin (PHA) and concanavalin A (Con A) at 10-50 IU of hCG/ml (P less than 0.05). hCG inhibited poorly the response of PBM to pokeweed mitogen (PWM) at concentration up to 100 IU/ml. When monocytes were removed from the PBM population with columns of Sephadex G10 the inhibitory effect of hCG on PHA- and Con A-induced lymphoproliferation was reduced, with inhibition occurring only at a level of 100 IU of hCG/ml. These results suggest that hCG does not inhibit equally the proliferative response of all lymphocyte subsets and further that cells of the monocyte/macrophage series may play a role in its action on lymphocyte proliferation. PMID- 4020779 TI - Pregnant and pseudopregnant mice produce a low cytotoxic alloantibody response when challenged by fetal but not adult F1 alloantigens. AB - The tertiary cytotoxic alloantibody response of syngeneically pregnant, pseudopregnant and non-pregnant BALB/c mice immunised with semi-allogeneic lymphocytes from fetal and adult (CBA X BALB/c)F1 donors was investigated by the microcytotoxicity method. The pregnant and pseudopregnant animals showed a significantly lower response to fetal alloantigens compared to that towards adult alloantigens (P less than 0.001). In contrast, control non-pregnant recipients showed no diminution of response to fetal alloantigens. These observations suggest that the hormonal status of pregnancy, even in the absence of a conceptus, permits a low cytotoxicity antibody response when challenged specifically by fetal, but not when challenged by adult, F1 alloantigens. PMID- 4020780 TI - Immunocytochemical localization of antibody during placental transmission of immunity in rats. AB - Autologous anti-horseradish peroxidase antibody has been localized in pregnant rats at various levels through placental membranes en passage to fetal circulation. The antibody was complexed in situ with the antigen and the resulting complex was made visible electron microscopically by immunohistochemical techniques. Visceral yolk-sac membranes from fetuses during the last half of gestation, viz. at 12, 17, and 22 days gestation, were so examined; differences were noted in the localization of cytochemical reaction product at increasing gestational ages. In yolk-sac endodermal epithelium at 12 days, the product was identified on receptor areas at the free surface of the epithelium, in a system of endocytosed clathrin-coated vesicles, or endosomes, within a closely related apical canalicular system, and stored in subapical vacuoles. Uptake and storage appeared markedly reduced in membranes taken at 17 days and was least apparent at 22 days (the day before term). Moreover, the product of antibody localization was not identified in the apical canaliculi at the two later stages. It is believed that most antibody had been hydrolyzed by these later stages. However, at the latest stage, reaction product also was identified in small vesicles in the basal cytoplasm of the endodermal epithelium and in the endothelium of vitelline (i.e., fetal) capillaries. These morphological results suggest that during the latter half of pregnancy antibody is absorbed; it is stored and hydrolyzed early on, and is transferred to fetal circulation only near term, a conclusion in close accord with what is known physiologically about prenatal transmission of immunity in this species. PMID- 4020781 TI - Immunoglobulin G in the decidua basalis and metrial gland of the pregnant mouse uterus. AB - The distribution of immunoglobulin G (IgG) in the decidua basalis and metrial gland of the mouse uterus at days 10 and 14 of pregnancy has been investigated using immunohistochemical methods. IgG was found in the intercellular spaces but none was found in decidual cells, stromal cells of the metrial gland or granulated metrial gland cells. These results differ from those of other studies which have localised IgG in the cytoplasm of rat granulated metrial gland cells. PMID- 4020782 TI - Diagnosis of genital Mycoplasma and Ureaplasma infections. AB - Genital Mycoplasma and Ureaplasma have been implicated in pelvic inflammatory disease, puerperal infections, septic abortions, low birth weight, nongonococcal urethritis and prostatitis as well as spontaneous abortion and infertility. An unequivocal diagnosis of infection with these organisms can be made only after properly obtained specimens have been evaluated with the use of selective cultures. PMID- 4020783 TI - Assessing the number of genital chlamydial infections in the United States. AB - The prevalence and incidence of genital infections with Chlamydia trachomatis have not yet been determined for broadly based populations within the United States. Largely on the basis of results of prevalence studies from sexually transmitted disease clinics, it has been estimated that C. trachomatis infections are the most common of all sexually transmitted infections and may number 3-5 million cases annually. C. trachomatis isolation rates range from 50% to 80% in certain diseases known to be caused by Chlamydia and from 10% to 30% in sexually active female adolescents and approximately 5% in college women. Cheaper, more sensitive and widely available diagnostic tests are necessary to adequately define the epidemiology of genital Chlamydia infections in the U.S. PMID- 4020784 TI - Chlamydia trachomatis infection in women. AB - Chlamydia trachomatis is found worldwide and is probably the most common sexually transmitted disease, infecting both females and males, adults as well as children. The organism is responsible for a variety of infections in women- urethral syndrome, cervicitis, endometritis and salpingitis. C. trachomatis may colonize the lower genital tract and result in asymptomatic infection, ultimately resulting in sterility. In addition, infection of the female genital tract during pregnancy may result in spontaneous abortion, premature labor, postpartum endometritis, neonatal conjunctivitis or pneumonia. PMID- 4020785 TI - Mullerian dysgenesis. AB - The multifaceted syndrome of mullerian dysgenesis appears to represent a defect in mesodermal organization and is often associated with renal and skeletal anomalies. This report discusses the embryology, multifactorial etiology, clinical presentation and management of the syndrome from a historical standpoint and details our experience with 35 affected patients. Both Frank dilatation and McIndoe vaginoplasty appear to be acceptable means of therapy. The therapeutic success depends to a large extent on the psychosocial adaptation of the patient. PMID- 4020786 TI - Thermography as a risk indicator of breast cancer. Results of a study and a review of the recent literature. AB - Because of recent data suggesting that about 40% of patients with a positive thermogram may subsequently develop breast cancer, a review of the data from the Cincinnati Breast Cancer Detection Demonstration Project (BCDDP) was undertaken. Of the 1,260 patients with more than one positive thermogram from 1973 to 1976, 1.9% subsequently developed breast cancer from 1977 to 1983. That finding was not significantly different from the 1.3% of patients who developed cancer and never had a positive thermogram. A critical review of the recent literature on the subject reinforces the BCDDP findings. PMID- 4020787 TI - Comparison of amniotic fluid optical density, L/S ratio and creatinine concentration in predicting fetal pulmonary maturity. AB - The optical density of amniotic fluid at 650 nm (OD650) has been proposed as a rapid means of assessing fetal pulmonary maturity. Two hundred eighty-two amniotic fluid samples were analyzed for OD650, L/S ratio and creatinine concentration, and those values were related to the infants' pulmonary outcome. Among those infants delivered within 72 hours of amniocentesis, pulmonary maturity was predicted accurately in 98.3% by the OD650, 97.7% by the L/S ratio and 97.6% by the creatinine concentration. All three tests were unreliable in predicting pulmonary complications when the tests revealed pulmonary immaturity. OD650 values were found to vary inversely with centrifugation speed, reaffirming the need for standardized processing techniques to achieve reliable results. Marked discrepancies occurred between the diagnoses given by three neonatologists asked to retrospectively evaluate the likely etiology of pulmonary problems in nine infants suspected of having respiratory distress syndrome. PMID- 4020788 TI - Contraction stress testing with nipple stimulation. AB - The contraction stress test (CST) is used widely as a measure of fetoplacental respiratory reserve. With contractions traditionally induced by intravenous oxytocin, the test has been limited in its use by time, expense and patient discomfort. In a prospective evaluation of the effectiveness of nipple stimulation for the production of uterine contractions, a successful CST was obtained in 94% of the attempts, with a mean total test time of 12 minutes. PMID- 4020789 TI - High-risk obstetrics. The three-year experience of four subspecialists. AB - The development of maternal-fetal medicine as a subspecialty in obstetrics and gynecology is fairly new. The specialists involved in this area are usually hospital based and involved in multiple activities, including teaching, administration and research. The role of this subspecialist as a provider of primary care to a high-risk obstetric population is important but has not been reported on previously. In this context high-risk obstetrics refers to intercurrent obstetric problems, previous obstetric problems, previous medical problems, infertility and the supposedly high-risk group of physicians and physicians' wives. PMID- 4020790 TI - Clinical significance of focal pelvic endometriosis. AB - Clinical findings in a group of infertile patients with endometriosis were reviewed to determine if minimal (focal) disease exerted an effect on reproductive outcome. Focal disease, defined as isolated implants less than or equal to 5 mm without pelvic adhesions or anatomic distortion, was found in 69 patients, with 35% manifesting menstrual dysfunction/anovulation. Patients with focal disease were divided into two groups: those treated with danazol (400-800 mg) daily for six months and those not treated. Conception occurred in 71% of the danazol-treated patients and 30% of the untreated ones. These results suggest that focal endometriosis does influence reproductive performance and that infertile patients with focal disease should be treated more aggressively with the available medical regimens, particularly when the infertility is of significant duration or when routine therapy has failed. PMID- 4020791 TI - The CO2 laser for recurrent and therapy-resistant condylomata acuminata. AB - The medical records of 48 patients who underwent laser vaporization of therapy resistant or recurrent condylomata acuminata were studied with regard to history of immunosuppression, location of original lesion, type and duration of therapy, and whether magnification devices were used prior to or during therapy. The genitalia of the patients' sexual partners were examined in all cases in which the condylomata recurred after initial control of the lesions with conventional methods. In 46 of the 48 cases, possible reasons for the failure of conventional therapy could be found: unresponsive to chemical therapy (11 patients); reinfection by the sexual partner (4); immunosuppression (8); several factors (6); and incomplete eradication of the lesion (20). Thirty-eight of the 48 patients (79%) were treated successfully with one-time laser ablation of the lesions. Six patients with recurrent condylomata after laser therapy underwent a second laser treatment, and four of the six patients (total, 87%) have remained free of disease. The laser appears to be an effective method of treatment for recurrent or persistent condylomata acuminata provided that (1) the patient is not immunosuppressed, (2) the potentially infected sexual partner is examined and treated, if necessary, and (3) the external genitalia, including the anus, vagina and cervix, are carefully examined colposcopically to rule out the persistence of small lesions. PMID- 4020793 TI - Nonbacterial thrombotic endocarditis associated with severe preeclampsia and pulmonary artery catheterization. A case report. AB - A pulmonary artery catheter was placed in a parturient whose 33-week gestation was complicated by severe preeclampsia and pulmonary edema. Cesarean delivery was performed for both maternal and fetal indications. During the second postoperative day the patient developed disseminated intravascular coagulation; subsequently she experienced sudden cardiopulmonary arrest and died. Autopsy revealed multiple pulmonary thromboemboli and trivalvular nonbacterial thrombotic endocarditis. PMID- 4020792 TI - Influence of menstrual cycle variations on natural killer cytotoxicity and antibody-dependent cellular cytotoxicity to cells infected with herpes simplex virus. AB - Natural killer cytotoxicity (NKC) and antibody-dependent cellular cytotoxicity (ADCC) represent the ability of human leukocytes to destroy target cells. Those systems have been shown to influence herpes simplex virus (HSV) infections. Prostaglandins are known to inhibit these nonspecific immunologic defenses. Since prostaglandin production varies with the menstrual cycle, this study was undertaken to test for variations in cytotoxic activity against HSV-infected cells during the proliferative, secretory and menstrual phases in 13 normal volunteers. NKC and ADCC activity was not statistically different between the three menstrual phases when testing was done for both mononuclear and polymorphonuclear cells from donor sera. This study suggested that NKC and ADCC cannot be used to explain anecdotal experiences suggesting menstrual variations as a triggering mechanism for HSV recurrences. PMID- 4020794 TI - Oxygen--friend and foe. PMID- 4020795 TI - Prevention of recurrent spontaneous abortions by leukocyte transfusions. AB - One hundred and thirty-nine couples referred because of recurrent abortions with no obvious cause were assessed for genetic similarity using the HLA major histocompatibility system. Comparison with 103 fertile control couples demonstrated that a much higher proportion of couples in the abortion group shared two or more HLA antigens. Using this criterion, 44 wives out of the 139 couples referred, when compared with a child-bearing group, appeared to share a greater than expected number of histocompatibility antigens and were therefore considered suitable for treatment. Twenty-eight wives have received treatment with white cell infusions from erythrocyte-compatible donors and so far they have delivered 17 babies plus 2 second babies. Another 3 wives are pregnant beyond their previous dates for abortions (1 first and 2 second pregnancies). There have been 5 failures (4 first pregnancy and 1 second pregnancy); one of these was treated a second time and has now successfully delivered. Seven couples are awaiting conception. Of the patients who have become pregnant, 81.5% have had successful deliveries. No adverse transfusion reactions have been observed. PMID- 4020796 TI - Evaluation of the plain abdominal X-ray in the acute abdomen. AB - The prognostic value of an erect and supine abdominal X-ray was studied prospectively in 97 patients with an acute abdomen. Although 64 (66%) of the radiographs showed an abnormality, the surgical registrar altered his clinical diagnosis on only seven occasions and changed his management on four. A consultant radiologist was the most accurate at reporting the X-rays even without seeing the patient, whilst junior surgical and radiological staff were as accurate as each other. A surgical registrar, however, was more accurate than junior radiologists in making a diagnosis. The investigation was of immediate clinical value in only 4% of the patients, and its use could probably be limited without detriment to patients. PMID- 4020797 TI - Complications of saturation diving. AB - The experience of 458 man-dives with 731 excursions between 50 m and 300 m carried out by Royal Navy saturation divers is summarized. During saturation decompression there were 6 treated bends and 33 reported niggles. Two bends occurred in dives deeper than 249 m and the remaining 4 bends occurred in dives where decompression began in much less than the saturation stop time after completion of downward excursions. There was one case of vestibular system decompression sickness after an excursion to 300 m. It is concluded that the decompression table is effective in use shallower than 150 m but that the risk increases with greater depth. There is, however, only limited experience in the deeper range. There is no evidence that chamber compression with air to 10 m adversely affects decompression from deeper than 50 m. An account of the medical and physiological conditions affecting divers in these dives is given. PMID- 4020798 TI - Microcomputers in clinical research: discussion paper. PMID- 4020799 TI - Wormwood Scrubs Annexe--a therapeutic community within a prison: discussion paper. PMID- 4020800 TI - Cartesian dualism and the current crisis in medicine--a plea for a philosophical approach: discussion paper. PMID- 4020802 TI - Pelvic actinomycosis presenting with rectal stricture. PMID- 4020801 TI - Congenital adrenal hyperplasia and XYY hypogonadism. PMID- 4020803 TI - Headache due to ischaemic heart disease. PMID- 4020804 TI - Systemic lupus erythematosus with anticardiolipin antibodies and lupus anticoagulant syndrome. PMID- 4020805 TI - Munchausen's syndrome with multiple pulmonary manifestations. PMID- 4020806 TI - Validity of alternative allergy practices. PMID- 4020807 TI - Foreign body sensation in the throat. PMID- 4020808 TI - High-dose dihydrocodeine produces hyperalgesia. PMID- 4020809 TI - A haemorrhagic syndrome in recently weaned pigs ascribed to hypovitaminosis K. AB - An outbreak of a haemorrhagic syndrome involved recently weaned, mixed-breed pigs in a large piggery. The pigs were fed a pelleted complete ration containing antibacterial drugs. Affected pigs failed to grow, became pale and developed large, subcutaneous haematomas. Some pigs became lame and one had epistaxis. The monthly mortality rate in the weaner house, which was previously less than 2%, exceeded 6% during the outbreak. Coagulation time, activated partial thromboplastin time and prothrombin time were prolonged in blood from some of the pigs. The outbreak resolved promptly after supplementation of the diet with vitamin K3. PMID- 4020810 TI - Infertility in a Maltese poodle as a result of a sperm midpiece defect. AB - A 2 1/2-year-old Maltese poodle was examined for breeding soundness following a series of unsuccessful matings to fertile bitches. He was found to have only 8% normal sperm in his ejaculate when Spermac-stained smears were examined under the light microscope. The defect most frequently encountered involved the midpiece attachment, and the various manifestations of disintegration found in this region are described and illustrated. Transmission and scanning electron microscopy confirmed light microscopical findings. PMID- 4020811 TI - Suspected Tyzzer's disease in two foals. AB - Tyzzer's disease was diagnosed histologically in two foals, a 4-week-old Thoroughbred cross and a 6-week-old Arabian foal. Clinically both foals were in good health prior to a short illness lasting only a few hours. The liver lesions in both foals were characterized microscopically by multiple foci of necrosis. Variable numbers of elongated slender intracytoplasmic bacilli resembling Bacillus piliformis were demonstrated within hepatocytes bordering the necrotic foci. PMID- 4020812 TI - Endodontic therapy on an African lion (Panthera leo). AB - The endodontic therapy used on an African lion was similar to procedures performed on humans and other exotic animals with the same condition. The procedure involved removal of the pulpal tissue to the apex of the root in three canine teeth. The internal aspect of the root canal was sterilized and filled with a rubber-like material (gutta percha) which was cemented in place. Chrome cobalt alloy crowns were fabricated and cemented to the top two canine teeth. The lower canine tooth received a silver amalgam restoration. PMID- 4020813 TI - Treatment of malignant epulis in the dog. PMID- 4020814 TI - Mycotoxins. PMID- 4020815 TI - Preliminary results of non-surgical intra-uterine insemination of sheep with thawed frozen semen. AB - Non-surgical intra-uterine insemination was achieved in 70 of 97 ewes (72%). Of the 70 ewes in which intra-uterine thawed semen was deposited, a total of 50 ewes (71%) conceived. Routine use of this technique is not at present foreseen due to the complicated and time consuming nature of the procedure. PMID- 4020816 TI - Valsiekte (falling disease): a nervous disorder in lambs suspected of being caused by the plant Chrysocoma tenuifolia. AB - A description is given of the clinical signs and pathological changes in 23 field cases of valsiekte from the Bethulie region of the Orange Free State, Republic of South Africa. The disease, which occurred almost exclusively in 2-4 month-old Dorper or Dorper cross-bred lambs, was characterized by protracted ataxia, paresis and high mortality. Microscopical changes were consistently found in the neurons and white matter along the entire length of the spinal cord, and rarely in the medulla oblongata. These changes included vacuolation and degeneration of neurons, mainly of the lateral and ventral horns in the spinal cord, and a status spongiosus which was most noticeable in the lateral and ventral tracts of the spinal cord. All affected lambs had access to the plant, Chrysocoma tenuifolia (bitterbos), but trials to reproduce the condition by dosing the plant, were not successful. PMID- 4020817 TI - Blood chemical and electrolyte concentrations in the ostrich Struthio camelus. AB - Serum levels of sodium, potassium, chloride, phosphorus, iron, total magnesium, total calcium, alkaline phosphatase, alanine transaminase, lactate dehydrogenase, creatine kinase, gamma-glutamyltransferase, aspartate transaminase, urea, creatinine, total protein, albumin and plasma glucose were determined in 49 ostriches (Struthio camelus) kept under semi-extensive conditions. PMID- 4020818 TI - Different banding techniques for the study of bovine chromosomes. AB - The different banding techniques R-, Q-, C-, NOR- and G-banding allow the identification of individual chromosomes in cattle with greater accuracy than with undifferentiated Giemsa staining. These techniques show characteristic bands on each chromosome and are therefore very useful and reliable for the detection of chromosomal abnormalities. PMID- 4020819 TI - [The incidence of clinical cases in a peri-urban farm animal practice]. AB - The incidence of clinical cases in farm animals encountered in the ambulatory practice at the Faculty of Veterinary Science, University of Pretoria, is discussed. In a 3 year period 4 013 clinical cases were seen; these did not include cases seen during herd examinations. The diagnoses made are grouped under infectious diseases (19,6%), nonspecific inflammatory conditions (17,3%), gastro intestinal conditions (9,7%), gynaecological conditions and procedures (14,5%), surgical conditions and procedures (26%), toxicological conditions (3,7%), metabolic diseases (1,5%), nutritional abnormalities (2,4%) and miscellaneous conditions. PMID- 4020820 TI - Thromboembolic meningoencephalitis diagnosed in Natal. AB - Nine feedlot cattle showed clinical signs consistent with those expected in thromboembolic meningoencephalitis. These signs included pyrexia, ataxia, posterior paresis, paralysis and coma. Brown necrotic foci with haemorrhagic borders were observed in the brains of three animals that had died. In these foci vasculitis, thrombosis, infarction and neutrophil infiltration were observed during microscopical examination. Haemophilus somnus was isolated in pure culture from the brains. PMID- 4020821 TI - Guidelines for bacterial counts on carcases at Cato Ridge abattoir. AB - The agar sausage technique was used to make an assessment of the surface aerobic bacterial levels of refrigerated beef, mutton and pork carcases at Cato Ridge abattoir by taking agar imprints from selected sites on the surfaces of carcases. It was shown that half of the 297 beef carcases examined had less than 200 aerobes cm-2, half of the 298 mutton carcases less than 250 aerobes cm-2 and half the 299 pork carcases less than 134 aerobes cm-2. These counts are utilised as guidelines to identify breakdowns in hygiene at the abattoir. PMID- 4020822 TI - Psoralenamines. 3. Synthesis, pharmacological behavior, and DNA binding of 5 (aminomethyl)-8-methoxy-, 5-[[(3-aminopropyl)oxy]methyl]-, and 8-[(3 aminopropyl)oxy]psoralen derivatives. AB - A series of derivatives of 5-(aminomethyl)-8-methoxypsoralens, 8-[(3 aminopropyl)oxy]psoralens, and 5-[[[3-(tri-methylammonio)propyl]methyl]-8 methoxypsoralen has been synthesized and their potential as PUVA reagents examined. While the DNA association constants of selected psoralens were found to be 10(5)-10(6)L mol-1, corresponding to efficient binding, flow linear dichroism studies indicated that only the 8-substituted psoralens bind to DNA by intercalation. Furthermore, the ability to photoinduce interstrand cross-links in calf thymus DNA, in vitro, was as efficient as that of 8-methoxypsoralen for the 8-substituted psoralens, which were up to 25 times as efficient as the 5 substituted psoralens. Four of the psoralens studied were radiolabeled and used to study photobinding to DNA. Analogously to the cross-binding results, the 8 substituted psoralens were more efficiently photobound than the 5-substituted, while only slight differences were found in the photobinding-cross-linking ratio. The photoreactivity of the aminopsoralens toward cyclohexene and 2' deoxythymidine was enhanced compared to that of 8-methoxypsoralen, the effect being most pronounced when the amino group is close to the furocoumarin ring system. Most of the new compounds were less photocytotoxic than 8-methoxypsoralen to NHIK 3025 cells, in vitro, and they caused less light-induced DNA interstrand cross-linking, in situ, in these cells. A clear correlation between the photocytotoxicity and the DNA cross-linking ability of the psoralens was observed. Several of the derivatives showed more pronounced effects in the light dependent skin thickening (inflammatory) test on mice than 8-methoxypsoralen. No correlation between DNA cross-linking capacity, in vitro, and skin phototoxicity was found for this series of psoralens. PMID- 4020823 TI - Synthesis and biological activity of 6-azacadeguomycin and certain 3,4,6 trisubstituted pyrazolo[3,4-d]pyrimidine ribonucleosides. AB - Several 3,4,6-trisubstituted pyrazolo[3,4-d]pyrimidine ribonucleosides were prepared and tested for their biological activity. High-temperature glycosylation of 3,6-dibromoallopurinol with 1-O-acetyl-2,3,5-tri-O-benzoyl-D-ribofuranose in the presence of BF3 X OEt2, followed by ammonolysis, provided 6-amino-3-bromo-1 beta-D-ribofuranosylpyrazolo-[3,4-d]pyrimidin-4(5H)-on e. Similar glycosylation of either 3-bromo-4(5H)-oxopyrazolo [3,4-d]pyrimidin-6-yl methyl sulfoxide or 6 amino-3-bromopyrazolo [3,4-d]pyrimidin-4(5H)-one, and subsequent ammonolysis, also gave 7a. The structural assignment of 7a was on the basis of spectral studies, as well as its conversion to the reported guanosine analogue 1d. Application of this glycosylation procedure to 6-(methylthio)-4(5H) oxopyrazolo[3,4-d]pyrimidine-3-carboxamide gave the corresponding N-1 glycosyl derivative. Dethiation and debenzoylation of 16a provided an alternate route to the recently reported 3-carbamoylallopurinol ribonucleoside thus confirming the structural assignment of 16a and the nucleosides derived therefrom. Oxidation of 16a and subsequent ammonolysis afforded 6-amino-1-beta-D-ribofuranosyl-4(5H) oxopyrazolo[3, 4-d]pyrimidine-3-carboxamide. Alkaline treatment of 15a gave 6 azacadeguomycin. Acetylation of 15a, followed by dehydration with phosgene, provided the versatile intermediate 6-amino-1-(2,3,5-tri-O-acetyl-beta-D ribofuranosyl)-4(5H)-oxopyrazolo [3, 4-d]pyrimidine-3-carbonitrile. Deacetylation of 19 gave 6-amino-1-beta-D-ribofuranosyl-4(5H)-oxopyrazolo[3, 4-d]pyrimidine-3 carbonitrile. Reaction of 19 with H2S gave 6-amino-1-beta-D-ribofuranosyl-4(5H) oxopyrazolo[3, 4-d]pyrimidine-3-thiocarboxamide. All of these compounds were tested in vitro against certain viruses and tumor cells. Among these compounds, the guanosine analogues 7a and 20a showed significant activity against measles in vitro and were found to exhibit moderate antitumor activity in vitro against L1210 and P388 leukemia. 6-Azacadeguomycin and all other compounds were inactive against the viruses and tumor cells tested in vitro. PMID- 4020824 TI - Syntheses and evaluation as antifolates of MTX analogues derived from 2, omega diaminoalkanoic acids. AB - Methotrexate (MTX) analogues 27a-c bearing 2, omega-diaminoalkanoic acids (ornithine and its two lower homologues) in place of glutamic acid were synthesized by routes proceeding through N2-[4-(methylamino)benzoyl]-N omega [(1,1-dimethylethoxy)carbonyl]-2, omega-diaminoalkanoic acid ethyl esters and N2 [4-(methylamino)benzoyl]-N5-[(1,1-dimethylethoxy)carbonyl]-2, 5-diaminopentanoic acid followed by alkylation with 6-(bromomethyl)-2, 4-pteridinediamine hydrobromide. Reactions at the terminal amino group of 27-type analogues or of appropriate precursors led to other MTX derivatives whose side chains terminate in ureido, methylureido, N-methyl-N-nitrosoureido, N-(2-chloroethyl)-N nitrosoureido, and 4-chlorobenzamido groups. Also prepared were unsymmetrically disubstituted ureido types resulting from addition of ethyl isocyanatoacetate and diethyl 2-isocyanatoglutarate to the ethyl esters of 27a,b. Of these ureido adducts (32a,b and 33a,b, respectively), only 33a was successfully hydrolyzed to the corresponding pure acid, in this instance the tricarboxylic acid 34, a pseudo peptide analogue of the MTX metabolite MTX-gamma-Glu. Biological evaluations of the prepared compounds affirmed previous findings that the gamma-carboxyl is not required for tight binding to dihydrofolate reductase (DHFR) but is operative in the carrier-mediated transport of classical antifolates through cell membranes. High tolerance levels observed in studies against L1210 leukemia in mice suggest the reduced potency may be due not only to lower transport efficacy but also to loss of the function of intracellular gamma-polyglutamylation. The N-nitrosoureas 30 and 31 showed appreciable activity in vivo vs. L1210, but the activity did not appear to be due to antifolate action as evidenced by their poor inhibition of both L1210 DHFR and cell growth in vitro. PMID- 4020826 TI - Synthesis and antitumor activity of structural analogues of the anticancer benzophenanthridine alkaloid fagaronine chloride. AB - The indenoisoquinoline analogue 4 of fagaronine chloride (2) has been prepared, as well as its positional isomer 20 and the corresponding mesylated derivatives 16 and 19. Compounds 4, 16, and 20 were tested against P388 lymphocytic leukemia and found to possess significant activity. A tricyclic analogue 24 was also synthesized and was devoid of cytotoxicity in the KB cancer cell culture system. The change in the substitution pattern of the A-ring on going from 4 to 20 was tolerated without producing a significant decrease in antitumor activity. PMID- 4020825 TI - Synthesis and antitumor activity of tropolone derivatives. 2. AB - Structural requirement for antitumor activity of tropolone derivatives 2-4 was explored. Isochroman derivatives (6-17, 20, and 23) and alpha, alpha disubstituted compounds 26-30 were synthesized and their antitumor activities were tested. These nontroponoid derivatives were all inactive, implying that a tropolone ring is essential for the activity. Several compounds related to the monotropolone analogue 3 were synthesized. Among them, 31-33 showed significant activity, but their potencies were considerably weaker than those of binary tropolone analogues 4. PMID- 4020827 TI - Synthesis and antiinflammatory and analgesic activity of 5-aroyl-1,2-dihydro-3H pyrrolo[1,2-a]pyrrole-1-carboxylic acids and related compounds. AB - 5-Acyl-1,2-dihydro-3H-pyrrolo[1,2-a]pyrrole-1-carboxylic acids and the homologous pyridine and azepine derivatives were synthesized and assayed for antiinflammatory and analgesic activity. 5-Benzoyl-1,2-dihydro-3H-pyrrolo-[1,2 a]pyrrole-1-carboxylic acid and the corresponding p-methoxy compound 74 were selected for evaluation as analgesic agents in humans on the basis of their high potency in the mouse phenylquinone writhing assay as well as on their minimal liability to elicit gastrointestinal erosion in rats on chronic administration. Extensive quantitative structure-activity relationship (QSAR) studies of the benzoylpyrrolopyrrolecarboxylic acids have demonstrated that the analgesic (mouse writhing) and antiinflammatory (rat carrageenan paw) potencies of these compounds are satisfactorily correlated with the steric and hydrogen-bonding properties of the benzoyl substituent(s). The 4-vinylbenzoyl compound 95, which was correctly predicted to be highly active in both assays on this basis, is undergoing advanced pharmacological evaluation in animals as a potential antiinflammatory agent. PMID- 4020828 TI - Vinblastin-23-oyl amino acid derivatives: chemistry, physicochemical data, toxicity, and antitumor activities against P388 and L1210 leukemias. AB - The dimeric alkaloids vinblastine (VLB) and vincristine (VCR) differ structurally only in the functional group on the dihydroindole nitrogen. The semisynthetic derivative vindesine (VDS) differs slightly from VLB by having an amide group instead of an ester group. However, these minor distinctions are responsible for profound differences in the oncolytic spectrum, potency, and toxicity of these compounds. Vinblastin-23-oyl amino acid derivatives were synthesized by linking amino acid carboxylic esters to the vinblastin-23-oyl moiety through an amide linkage. Studies were extended to explore the influence of the nature of the amino acid, the ester alkyl chain lengths, the stereoisomerism of the amino acid, or the reacetylation of the hydroxyl group (position O-4) of the vindoline moiety. The present study deals with the synthesis of 21 vinblastin-23-oyl amino acid derivatives, some of their physicochemical data, the acute toxicity in mice, and therapeutic activities of these derivatives against the P388 and L1210 leukemias in comparison with VDS, VBL, and VCR. PMID- 4020829 TI - Decomposition reactions of (hydroxyalkyl) nitrosoureas and related compounds: possible relationship to carcinogenicity. AB - (Hydroxyalkyl)nitrosoureas and the related cyclic carbamates N nitrosooxazolidones are potent carcinogens. The decompositions of four such compounds, 1-nitroso-1-(2-hydroxyethyl)urea (I), 3-nitrosooxazolid-2-one (II), 1 nitroso-1-(2-hydroxypropyl)urea (III), and 5-methyl-3-nitrosooxazolid-2-one (IV), in aqueous buffers at physiological pH were studied to determine if any obvious differences in decomposition pathways could account for the variety of tumors obtained from these four compounds. The products predicted by the literature mechanisms for nitrosourea and nitrosooxazolidone decompositions (which were derived from experiments at pH 10-12) were indeed the products formed, including glycols, active carbonyl compounds, epoxides, and, from the oxazolidones, cyclic carbonates. Furthermore, it was shown that in pH 6.4-7.4 buffer epoxides were stable reaction products. However, in the presence of hepatocytes, most of the epoxide was converted to glycol. The analytical methods developed were then applied to the analysis of the decomposition products of some related dialkylnitrosoureas, and similar results were obtained. The formation of chemically reactive secondary products and the possible relevance of these results to carcinogenesis studies are discussed. PMID- 4020830 TI - Structure-activity relationship in PAF-acether. 2. rac-1-O-Octadecyl-2-O-acetyl-3 O-[gamma-(dimethylamino)propyl]glycerol . AB - Two products without phosphoryl groups, 1-O-octadecyl-2-O-acetyl-3-O-[gamma (dimethylamino)propyl]glycerol and its quaternary salt, were synthesized from 1-O octadecyl-2-O-benzylglycerol. In comparison with PAF-acether, they lost aggregating and bronchoconstrictive activities and did not show any antagonistic effects. PMID- 4020831 TI - Correlation of structure and activity in ansamycins: structure, conformation, and interactions of antibiotic rifamycin S. AB - The crystal and molecular structure of the DNA-dependent RNA polymerase inhibiting antibiotic rifamycin S (C37H45O12N) as a dihydrate has been determined, and the conformation necessary for activity has been correlated with those of other active rifamycins. The orthorhombic unit cell, space group P212121 with dimensions of a = 13.010 (2), b = 14.236 (2), c = 20.571 (4) A, contains 4 molecules. The structure was solved by a combination of vector search and direct methods and refined anisotropically to an R factor of 0.048 for 2855 reflections. The conformation of the ansa chain differs from those of rifampicin and rifamycin B but resembles that of rifamycin SV at the joining points, C(2) and C(12), of the ansa chain to the naphthoquinone chromophore. The middle part of the ansa chain, which is essential for its activity against the enzyme, has the same conformation as other active rifamycins. The effect of the 3-substitution on the ansa chain conformation is that the carboxyl (C(15) = O) group wings around the N C(16) direction, depending upon the electronegativity of the 3-substituent. The hydrogen bonding involves O(1), O(2), O(8), O(9), O(10), and the water molecules. A possible four-stage model for the interaction of the rifamycins with the enzyme DNA-dependent RNA polymerase has been speculated. PMID- 4020832 TI - Stereoselective antitumor properties in the Lewis lung carcinoma model using bis(morpholinomethyl) derivatives of tricyclic bis(dioxopiperazines). AB - Geometric isomers of 2,11-bis(morpholinomethyl)tetrahydrodipyrazino[1,2-a:2',1' c]pyraz ine-1, 3,10,12-(2H,4H,9H,11H)-tetrone (3 and 4) and the parent bisimides (1 and 2) were studied for their stereoselective antimetastatic activity in the Lewis Lung carcinoma model. The morpholinomethyl cis-syn-trans isomer 4 was more effective as an inhibitor of metastasis than the other three analogues. Using a postamputation protocol, the order of decreasing activity was cis morpholinomethyl analogue 4 greater than trans morpholinomethyl analogue 3 greater than parent cis imide 2 greater than parent trans imide 1. Increased activity observed for the morpholinomethyl derivatives may reflect differences in solubility and delivery (prodrug) or an intrinsic antitumor activity of the morpholinomethyl-N functionality. PMID- 4020833 TI - Activity of platinum(II) intercalating agents against murine leukemia L1210. AB - Four series of intercalating, square-planar Pt(II) complexes derived from the ligands 2,2'-bipyridine, 2,2':6',2"-terpyridine, 1,10-phenanthroline, and 3,4,7,8 tetramethyl-1,10-phenanthroline were synthesized and aspects of their activity against murine leukemia L1210 cells investigated. The 2,2':6',2"-terpyridine thiolato complexes are growth inhibitory in culture, with IC50 values in the range 6-32 microM, and cause cell lysis at high concentrations. Of the remaining three series, the 2,2'-bipyridine complexes are the least potent in their effects. There is a general enhancement in activity on moving from the 1,10 phenanthroline complexes to the 3,4,7,8-tetramethyl-1,10-phenanthroline analogues. Flow cytometric analysis on representative complexes shows that they are not cell cycle specific. Alkaline elution experiments indicate no damage to DNA of cells exposed to (thiophenolato)(2,2':6',2"-terpyridine)platinum(II) chloride monohydrate and (ethylenediamine)(1,10-phenanthroline)platinum(II) dichloride dihydrate although (ethylenediamine)(3,4,7,8-tetramethyl-1,10 phenanthroline)platinum(II) dichloride dihydrate causes both single-strand breaks and DNA cross-links. Compounds 2a, 5a, and 6a showed no antitumor activity against L1210 in mice. PMID- 4020834 TI - Structural features of imidazole derivatives that enhance styrene oxide hydrolase activity in rat hepatic microsomes. AB - The present study is an investigation of the in vitro effects of several model imidazole compounds and three antifungal drugs on styrene oxide hydrolase activity in hepatic microsomes from control, PB-induced, and 3MC-induced rats. We first determined the influence of the position of substitution of a phenyl group in the imidazole or imidazoline ring on the ability of 10(-3) M concentration of the imidazole derivative to enhance microsomal epoxide hydrolase activity. This study showed that 1-phenylimidazole enhanced epoxide hydrolase activity to the greatest extent and that, for any one imidazole derivative, the extent of enhancement was similar for microsomes from untreated, PB-induced, or 3MC-induced rats. We next studied the potency and maximum effectiveness of several N-1 substituted imidazole derivatives with differing lipophilicities and pKa values. Hansch analysis showed that potency for activating epoxide hydrolase correlated with both lipophilicity and electron-withdrawing effects of imidazole ring substituents. The most potent compounds had aryl or aralkyl substitutents at the 1-position of imidazole and pKa in the range 7-9 and were clotrimazole, ketoconazole, miconazole, 1-benzylimidazole, and 1-(4-hydroxyphenyl)imidazole. These compounds enhanced styrene oxide hydrolase by 100% at concentrations less than 2 X 10(-4)M. 1-Benzylimidazole increased both Km and Vmax and abolished the inhibition observed at high concentrations of styrene oxide. PMID- 4020835 TI - Synthesis and antineoplastic evaluations of 5,8-bis[(aminoalkyl)amino]-1 azaanthracene-9,10-diones. AB - Several 5,8-bis[(aminoalkyl)amino]-1-azaanthracene-9,10-diones have been synthesized and evaluated for antitumor activity against L1210 leukemia both in vitro and in vivo. Comparisons are made to the corresponding carbocyclic analogues. One of the aza analogues showed modest in vivo activity. PMID- 4020837 TI - Potential radiosensitizing agents. 7. 4(5)-Iodo-5(4)-nitroimidazole derivatives. AB - A series of 4(5)-iodo-5(4)-nitro-1-substituted-imidazoles has been synthesized and tested for their ability to selectively radiosensitize hypoxic Chinese hamster cells (V-79) to the lethal effect of radiation. The reaction of 4(5)-iodo 5-(4)-nitroimidazole with 1,2-epoxy-3-methoxypropane and ethyl alpha chloroacetate produced two isomeric products in each case, which were identified by their NMR spectra. The ethyl esters were further reacted with 3-picolylamine to produce corresponding amides. The 5-iodo-4-nitroimidazole-1-N-(3 picolyl)acetamide on further reaction with m-chloroperbenzoic acid produced the corresponding N-oxide. These compounds were generally more toxic to V-79 cells than the 2-nitroimidazole derivatives and were found to be more effective radiosensitizers in vitro. The 5-iodo-4-nitroimidazole derivatives were more efficient as sensitizers than the 4-iodo-5-nitroimidazole derivatives, and the sensitizing efficiency of this class of agents was found to have significant correlation with their partition coefficients. PMID- 4020836 TI - Pilocarpic acid esters as novel sequentially labile pilocarpine prodrugs for improved ocular delivery. PMID- 4020838 TI - Substrate probes for the mechanism of aromatic hydroxylation catalyzed by cytochrome P-450: selectively deuterated analogues of warfarin. AB - Optically pure analogues of (R)- and (S)-warfarin selectively deuterated in either the 6-, 7-, or 8-position were prepared and incubated with microsomal preparations from either nontreated, phenobarbital-pretreated, or beta naphthoflavone-pretreated male Sprague-Dawley rats. The amount of deuterium retained and the relative amount of hydroxylated product formed (6-, 7-, 8-, or 4'-hydroxywarfarin) from each of the six substrates for each of the treatments were determined by capillary gas chromatography-mass spectrometry. The degree of deuterium retention in all products from all substrates was largely independent of both absolute configuration and induction state. Conversely, the relative amounts of product formed were highly dependent upon both absolute configuration and induction state. These results suggest that all the hydroxylation reactions proceed through an addition rearrangement step prior to or in the absence of epoxide formation, which appears to be dictated by the nature of the heme-Fe3+ oxene complex. In contrast, the position of hydroxylation or regioselectivity appears to be primarily dependent upon the nature of the apoprotein. PMID- 4020839 TI - Medical problem-solving: a critique of the literature. AB - Descriptive studies of clinical reasoning have been based primarily on an information-processing paradigm that has entailed microscopic analyses of the verbal behavior of small numbers of persons confronted with the task of making a diagnosis of a patient with symptoms of acute illness. From these studies, researchers have generally concluded: that medical problem-solving is an hypothetico-deductive process and that performance is not generalizable across problems. The author of the present paper argues that this narrow approach casts serious doubt on the validity of the conclusions and leaves unilluminated a large portion of the cognitive process involved in decisions about patient care. On the other hand, prescriptive, decision-analysis studies of medical problem-solving have generally been based on sophisticated decision theory that involves calculation and manipulation of complex probability and utility values in order to arrive at optimal decisions that will maximize patient benefits. While these prescriptive studies offer a methodology for improving clinical judgment, that methodology may not be one which decision-makers find attractive or feasible to employ. PMID- 4020840 TI - A comparison of medical students' performances in independent study and traditional programs. AB - Medical students at Ohio State University may study the basic medical sciences in an independent study program or in a conventional lecture-discussion program. In a study involving more than 2,000 students over a 10-year period, students pursuing the independent study program and students in the more traditional program performed similarly on Part I of the National Board of Medical Examiners (NBME) examinations and in their required clerkships. However, differences were identified in some content areas and resulted in curricular changes. PMID- 4020841 TI - The relationship between stress and attitudes toward leisure among first-year medical students. AB - The purpose of the study reported in this article was to examine first-year medical students' attitudes toward their free time and how these attitudes relate to self-reported stress levels. Members of the entering class of 1982-83 at the Southern Illinois University School of Medicine were asked to complete surveys designed to measure perceived stress and leisure attitudes. The results indicated a significant negative correlation between the total leisure scale and the stress scale. This correlation supported the hypothesis that students who perceived that they had high stress levels scored low on the leisure attitude scale. These findings suggest a need for educating students about the benefits of well spent leisure time as a stress management mechanism that is important in coping with daily pressures and anxieties. PMID- 4020842 TI - Congruence between curriculum goals and students' perceptions of learning environment. AB - The authors' main objectives in the study reported here were to assess medical students' perceptions of the learning environments provided by fourth-year clinical electives taken at three different training sites and to determine whether differences in learning environment among the sites could be attributed to differences in curricular goals. The investigators used a survey containing 32 items subdivided into six subscales: structure, interpersonal relationships, educational climate, practicality, enthusiasm, and humanism. Perceptions of the elective learning environment were obtained from 67 students. Overall differences among training sites as perceived by the students were found by means of a multivariate analysis of variance to be statistically significant. Further analysis revealed site differences on four subscales: structure, interpersonal relations, educational climate, and practicality. Implications of these findings and suggestions for future research are discussed. PMID- 4020843 TI - Evaluation of simultaneous teaching of extremities in gross anatomy program. AB - A gross anatomy program was designed to expose medical students to all areas of the body but shortened the dissection time on the extremities by having half the class dissect either the upper or lower extremity and then study the opposite extremity already dissected by other classmates. The program has been used for six years and was evaluated via an analysis of covariance by comparing the intramural examination performance on both the dissected and undissected extremities. There was no statistical difference in the students' performances regardless of the extremity dissected. The program was also evaluated externally by student performance on Part I of the examinations of the National Board of Medical Examiners. Students (n = 191) performed at the national average (69 percent) on all gross anatomy questions and on those questions pertaining to either extremity (66 percent). The program has efficiently utilized laboratory time with no measurable change in performance by six medical classes. PMID- 4020844 TI - Relationship between specialty choice and academic performance. PMID- 4020845 TI - Academic clinicians without residency training programs. PMID- 4020846 TI - A miniworkshop method for teaching medical students recognition of personality disorders. PMID- 4020847 TI - Assessment of interpersonal skills and humanistic qualities in medical residents. PMID- 4020848 TI - The use of written simulations and trained patients to evaluate a course in rheumatology. PMID- 4020849 TI - The antagonism of tetracycline and ferric iron in vivo. AB - To test the hypothesis that the in-vivo antibiotic action of tetracycline might be affected by ferric iron and the enhancement of infection by ferric iron by tetracycline, the actions of intraperitoneal antibiotic and local ferric ammonium citrate, given separately and together, were measured in the dorsal skin of guinea-pigs bearing lesions due to staphylococci, streptococci, a Proteus sp., an Erysipelothrix sp., Clostridium perfringens, Pseudomonas aeruginosa, Aeromonas hydrophila and Klebsiella pneumoniae. Tetracycline, given in two intraperitoneal doses of 25 mg/kg at 0 and 2 h after intracutaneous challenge, maintained plasma concentrations of 4-6 micrograms/ml for more than the first 4 h of infection, after which the local lesions had become largely insusceptible to the antibiotic. The intracutaneous injection of Fe 10 micrograms in a volume of 0.1 ml containing the bacteria was sufficient to enhance infection by those strains susceptible to this effect. The in-vivo efficacy of tetracycline was not always related to low MIC; a low MIC was sometimes associated with little action and a high MIC with moderate action. Sixteen organisms were tested. The iron diminished the tetracycline effect only feebly with one staphylococcal strain and the strain of E. rhusiopathiae. In only one case, with a strain of Proteus sp., was the tetracycline action grossly diminished. On the other hand, tetracycline diminished the enhancement effect of iron moderately with three strains of staphylococci and one strain each of K. pneumoniae, P. aeruginosa and C. perfringens, and strongly with two strains of staphylococci, a group-C streptococcus and one strain each of K. pneumoniae, E. rhusiopathiae and A. hydrophila. It is evident that the diminution of tetracycline action by moderate excess of readily available Fe , whether endogenous or administered, is an unlikely event (three instances among the 16 tested) whereas the diminution of the infection-enhancing effect of iron by tetracycline is much more likely (12 instances among the 16). Insofar as a decrease in iron available for enhancement of infection is valid evidence of a diminution of the iron available for necessary physiological processes of the subject treated, our results suggest that these processes might be affected by tetracycline. PMID- 4020850 TI - Human peripheral blood monocytes are susceptible to interferon-activated natural killer cells. AB - Monocytes and lymphocytes from peripheral blood were tested for their susceptibility to the natural killer (NK) cell activity of allogeneic and autologous lymphocytes. Peripheral blood monocytes, but not lymphocytes, were sensitive to the cytotoxic activity of interferon (IFN) activated NK cells. Allogeneic as well as autologous monocytes were sensitive to NK activity, although the killing seemed to be more pronounced in allogeneic combinations. The cells expressing cytotoxic activity for blood monocytes were found to conform to the characteristics of NK cells in the sense that they were activated by IFN, as well as in the sense that they were contained in the same cell fraction as large granular lymphocytes. PMID- 4020851 TI - Influence of avidity of circulating anti-DNA antibodies on murine lupus nephritis. AB - We determined the avidity of antiDNA antibodies in plasma of NZB/W mice when nephritis became apparent, when such mice developed chronic glomerulonephritis, and in mice whose nephritis was arrested, or attenuated, by immunosuppression. Antibody avidity was estimated by the rate of dissociation of 125IDNA-antiDNA complexes when excess unlabelled DNA was added to the plasma. In all groups of mice studied, the relative contributions of high and low avidity antiDNA antibodies were comparable and, overall, high avidity antibodies predominated. The results indicate that the avidity of circulating antiDNA antibodies did not reflect the extent and type of glomerular involvement, and was not predictive of clinical course. PMID- 4020852 TI - Erythrocyte deformability changes in autoimmune hemolytic anemia during development of NZB mice and their (NZB/NZW)F1 hybrid. AB - NZB and B/W hybrid mice develop compensated hemolytic anemia during the first year of their life. By the age of 3-5 months, their erythrocytes show evidence of spherocytosis, increased osmotic fragility and decreased whole cell deformability, as measured by ektacytometry, a laser diffraction technique. The presence of spherocytes with decreased surface area/volume ratio was confirmed by scanning electron microscopy and osmotic gradient ektacytometry. Whereas these abnormalities persisted and worsened in the NZB mice with further growth, they gradually improved and reverted to normal by the age of 12 months in B/W mice. This spontaneous improvement seems to be due to the accumulation of red cell membrane lipids reflecting the lipemia of immune complex nephritis in B/W mice. The implications of these findings in the modulation of autoimmune hemolytic anemia are discussed. PMID- 4020853 TI - Changes in specific immunoglobulins after various forms of portal diversion in the rat. AB - This study was designed to investigate further the hyperglobulinaemia which followed portal or splenic venous diversion but not mesenteric venous diversion. It was observed that levels of IgG and IgM were elevated from 3-6 weeks after portacaval shunt, portacaval transposition or splenacaval shunt. IgA levels were increased after all forms of portal venous diversions including after mesentericocaval shunt. The failure of levels of IgG and IgM to rise after mesocaval shunting suggests that some component of splenic venous blood may regulate the ability of the reticulo-endothelial system of the liver to respond to antigenic influences. PMID- 4020854 TI - Morphological and physiological studies of rat kidney cortex slices undergoing isosmotic swelling and its reversal: a possible mechanism for ouabain-resistant control of cell volume. AB - Slices of rat kidney cortex were induced to swell by preincubation at 1 degree C in an isotonic Ringer's solution, and their capacity to reverse swelling, by net extrusion of cellular water, was studied during subsequent incubation at 25 degrees C. The recovery from swelling was prevented by the respiratory inhibitor, antimycin A. On the other hand, extrusion of water was little affected by ouabain. The extrusion of water continuing in the presence of ouabain (but not that in its absence) was significantly reduced when furosemide was added or when medium Cl- was replaced by NO-3 or I-. There was substantial variability in the morphological appearance of cells within the cortical slices. Different segments of the nephron showed different structural changes during swelling and its reversal, the proximal tubules being most markedly affected. Proximal tubular cells of swollen slices showed disorganization of brush borders and expansion of their apical surfaces, and contained vesicles in their apical cytoplasm. Upon recovery at 25 degrees C, the apical portions of these cells showed reversal of the expansion, but some apical vesicles remained. These vesicles were much more numerous after recovery in the presence of ouabain, but they were much reduced in numbers, or totally absent, when recovery took place in the presence of furosemide or absence of Cl-, with or without ouabain. The vesicles seen in the presence of ouabain alone appeared to fuse with each other and with infoldings of the basolateral plasma membrane. Rather similar results were obtained with distal tubular cells in the slices. We suggest that volume regulation in the proximal and distal tubular cells proceeds by way of two mechanisms. The first consists of extrusion of water coupled to the ouabain-sensitive transport of Na+ and K+. The other proceeds by way of an ouabain-resistant entry of water into apical cytoplasmic vesicles, following furosemide-sensitive movements of Cl- and Na+; the vesicles then expel their contents by exocytosis at the basolateral cell borders. PMID- 4020855 TI - Are axoplasmic microtubules necessary for membrane excitation? AB - The excitability of the squid giant axon was studied as a function of transmembrane hydrostatic pressure differences, the latter being altered by the technique of intracellular perfusion. When a KF solution was used as the internal medium, a pressure difference of about 15 cm water had very little effect on either the membrane potential or excitability. However, within a few minutes after introducing either a KCl-containing, a KBr-containing, or a colchicine containing solution as the internal medium, with the same pressure difference across the membrane, the axon excitability was suppressed. In these cases, removal of the pressure difference restored the excitability, indicating that the structure of membrane was not irreversibly damaged. Electron-microscopic observations of these axons revealed that the perfusion with a KF solution or colchicine-containing solution preserves the submembranous cytoskeletal layer, whereas perfusion with a KCl or KBr solution dissolves it. These results suggest that the submembranous cytoskeletons including microtubules provide an important mechanical support to the excitable membrane but are not essential elements in channel activities. PMID- 4020857 TI - Stereological estimation of the volume-weighted mean volume of arbitrary particles observed on random sections. AB - A stereological estimator of the weighted mean volume of particles of arbitrary shape is described. This unbiased estimator is based on simple point-sampling of linear intercept lengths. The complete absence of shape assumptions effectively breaks the long-standing 'convexity-barrier': the only requirement here is that individual particles can be unambiguously identified by their profiles on random sections. Practical details of the simple estimation procedure and an example with very irregular particles are reported. Finally, an estimator of the variance of the weighted distribution of particle volume is discussed. This estimator is also valid for particles of arbitrary shape. For any mixture of ellipsoids (spheres, oblates, prolates and triaxial ellipsoids) the estimator is reduced to a simple function of measurements of diameters in the section plane. PMID- 4020856 TI - Thermotropic behavior of retinal rod membranes and dispersions of extracted phospholipids. AB - High sensitivity, differential scanning calorimetry studies of bovine retinal rod outer segment (ROS) disk membranes and aqueous dispersions of the extracted ROS phospholipids have been performed. ROS disk membranes were found to exhibit a broad peak of excess heat capacity with a maximum at less than about 3 degrees C, ascribable to a gel-to-liquid crystalline phase transition of a fraction of the phospholipids. A similar thermotropic transition was observed for aqueous dispersions of the total extracted and purified ROS phospholipids. Comparison of the results obtained for the dispersion of total ROS phospholipids to those of the purified head group fractions suggests that the thermotropic behavior reflects a gel-to-liquid crystalline transition, leading to lateral phase separation, involving those phosphatidylcholine (PC) molecules containing saturated fatty acyl chains, possibly together with the highest melting ROS phosphatidylethanolamine (PE) and phosphatidylserine (PS) components. The interpretation of the thermal behavior of the ROS disk membranes depends on whether the transition is assumed to derive from the ROS PC and/or PE/PS fractions, and whether the transbilayer arrangement of the ROS phospholipids is assumed to be symmetric or asymmetric. The calorimetric data can be simply explained in terms of an asymmetric distribution of the major ROS disk membrane phospholipids (G.P. Miljanich et al., J. Membrane Biol. 60:249-255, 1981). In this case, the transition would arise from the PE/PS fractions in the outer ROS disk membrane monolayer, and the anticipated transition from the PC in the inner monolayer would be broadened due to interaction with cholesterol. For the ROS membranes at higher temperatures, two additional, irreversible transitions are observed at 57 and 72 degrees C, corresponding to the thermal denaturation of opsin and rhodopsin, respectively. PMID- 4020858 TI - The 'bi-corpuscle' stereological problem: estimation of distributions of distances between paired spheres, from measurements in slabs showing overprojection and truncation, and its application to binucleated cells. AB - A non-parametric stereological method for the estimation of distributions of distances (d) between paired spheres of the same size, from the distances between their profiles observed in sections, is presented. The model accounts for sphere overprojection and truncation effects. Using the mean value of d (d), it is then possible, with simple formulae, to compute the probabilities of the co observation of two profiles from paired spheres with distance d between their centres, when at least one profile is observed. A useful application is the estimation of true binucleated cell frequencies from observations on tissue sections. An example for rat liver diploid cells is shown. The sphere distribution must be studied beforehand and, when the size variation is unacceptably large, implying that the assumption of a constant sphere radius is unreasonable, the main limitation of the model is met. PMID- 4020859 TI - Unbiased estimation of particle density in the tandem scanning reflected light microscope. AB - The tandem scanning reflected light microscope has the property of being able to obtain information from 'inside' solid objects by taking a thin optical section at the focal plane of the objective lens. This plane can be focused up and down through the specimen. We describe an unbiased 3-D counting rule for the TSRLM, which is applied to the estimation of osteocyte lacunar density in whole bone. This is shown to be an extremely efficient way of making such an estimate. Further possibilities for the application of the microscope in the field of stereology are discussed. PMID- 4020860 TI - Rat rabies in Mississippi. PMID- 4020861 TI - A community cancer program looks at carcinoma of the larynx. PMID- 4020862 TI - Procedures in family medicine: a survey. PMID- 4020863 TI - A polymorphic repetitive-sequence PR1 family. Evidence for meiotic instability. AB - When EcoRI digests of mouse genomic DNA were subjected to Southern blot analysis with the polymorphic repetitive sequence PR1 as a probe, one satellite-like band of 3.5 X 10(3) base-pairs, designated as PR1 family B, was detected in BALB/c strain mice, but not in the DDD/1- or MOA-strain mice. Analysis of recombinant phage clones revealed that the repeating unit of the PR1 family B was 13.5 X 10(3) base-pairs long. This family consisted of a tandem array of repeating units and occupied as much as 2% of one BALB/c chromosome. Since the BALB/c-specific PR1 family B is not present in DDD/1 or MOA mice, the unpaired portion of the BALB/c chromosome may be looped out in a synaptonemal complex during meiosis in F1 hybrids of the BALB/c strain with DDD/1 or MOA. To determine the fate of this extra DNA, we examined the genotypes of the F1 hybrid mice and of the segregating populations. Although the PR1 patterns of F1 and most N2 mice are consistent with typical Mendelian inheritance, some N2 progeny showed an abnormal 3.5 X 10(3) base-pair band of unexpectedly reduced intensity. This indicated that the extra DNA of PR1 family B occasionally underwent recombination during meiosis in F1 mice, resulting in its apparent excision. Examination of PstI digests supported this interpretation. PMID- 4020864 TI - Assembly-dependent conformational changes in a viral capsid protein. Calorimetric comparison of successive conformational states of the gp23 surface lattice of bacteriophage T4. AB - Inter- and intra-subunit bonding within the surface lattice of the capsid of bacteriophage T4 has been investigated by differential scanning calorimetry of polyheads, in conjunction with electron microscopy, limited proteolysis and sodium dodecyl sulfate/polyacrylamide gel electrophoresis. The bonding changes corresponding to successive stages of assembly of the major capsid protein gp23, including its maturation cleavage, were similarly characterized. The uncleaved/unexpanded surface lattice exhibits two endothermic transitions. The minor event, at 46 degrees C, does not visibly affect the surface lattice morphology and probably represents denaturation of the N-terminal domain of gp23. The major endotherm, at 65 degrees C, represents denaturation of the gp23 polymers. Soluble gp23 from dissociated polyheads is extremely unstable and exhibits no endotherm. Cleavage of gp23 to gp23* and the ensuing expansion transformation effects a major stabilization of the surface lattice of polyheads, with single endotherms whose melting temperatures (t*m) range from 73 to 81 degrees C, depending upon the mutant used and the fraction of gp23 that is cleaved to gp23* prior to expansion. Binding of the accessory proteins soc and hoc further modulates the thermograms of cleaved/expanded polyheads, and their effects are additive. hoc binding confers a new minor endotherm at 68 degrees C corresponding to at least partial denaturation of hoc. Denatured hoc nevertheless remains associated with the surface lattice, although in an altered, protease sensitive state which correlates with delocalization of hoc subunits visualized in filtered images. While hoc binding has little effect on the thermal stability of the gp23* matrix, soc binding further stabilizes the surface lattice (delta Hd approximately +50%; delta t*m = +5.5 degrees C). It is remarkable that in all states of the surface lattice, the inter- and intra-subunit bonding configurations of gp23 appear to be co-ordinated to be of similar thermal stability. Thermodynamically, the expansion transformation is characterized by delta H much less than 0; delta Cp approximately 0, suggesting enhancement of van der Waals' and/or H-bonding interactions, together with an increased exposure to solvent of hydrophobic residues of gp23* in the expanded state. These findings illuminate hypotheses of capsid assembly based on conformational properties of gp23: inter alia, they indicate a role for the N-terminal portion of gp23 in regulating polymerization, and force a reappraisal of models of capsid swelling based on the swivelling of conserved domains. PMID- 4020865 TI - The crystal structure of d(G-G-G-G-C-C-C-C). A model for poly(dG).poly(dC). AB - The structure of the DNA oligomer d(G-G-G-G-C-C-C-C) has been determined at a resolution of 2.5 A by single-crystal X-ray methods. There are two strands in the asymmetric unit, and these coil about each other to form a right-handed double helix of the A-type with Watson-Crick hydrogen bonds between base-pairs. The helix has a shallow minor groove and a deep, water-filled major groove; almost all exposed functional groups on the DNA are hydrated, and 106 ordered solvent molecules have been found. The two d(G-G-G-G).d(C-C-C-C) segments in the octamer exhibit similar and uniform structures, but there is a slight discontinuity at the GpC step between them. A recurring feature of the structure is the overlap of adjacent guanine bases in each GpG step, with the five-membered ring of one guanine stacking on the six-membered ring of its neighbour. There is little or no overlap between adjacent cytosine rings. Conformational parameters for these GpG steps are compared with those from other single-crystal X-ray analyses. In general, GpG steps exhibit high slide, low roll and variable twist. Models for poly(dG).poly(dC) were generated by applying a simple rotation and translation to each of the unmodified d(G-G-G-G).d(C-C-C-C) units. Detailed features of these models are shown to be compatible with various assays of poly(dG).poly(dC) in solution, and are useful in understanding the polymorphic behaviour of this sequence under a variety of experimental conditions. PMID- 4020866 TI - The pKa values of two histidine residues in human haemoglobin, the Bohr effect, and the dipole moments of alpha-helices. AB - Studies of abnormal and chemically modified haemoglobins indicate that in 0.1 M NaCl about 40% of the alkaline Bohr effect of human haemoglobin is contributed by the C-terminal histidine HC3(146) beta. In deoxyhaemoglobin, the imidazole of this histidine forms a salt bridge with aspartate FG1(94) beta, in oxyhaemoglobin or carbonmonoxyhaemoglobin it accepts a hydrogen bond from its own NH group instead. Kilmartin et al. (1973) showed that in 0.2 M-NaCl + 0.2 M-phosphate this change of ligation lowered the pKa of the histidine from 8.0 in Hb to 7.1 in HbCO, but Russu et al. (1980) claimed that in bis-Tris buffer without added NaCl its pKa in HbCO dropped no lower than 7.85, and that in this medium the C terminal histidine made only a negligible contribution to the alkaline Bohr effect. We have compared the histidine resonances of HbCO A with those of three abnormal haemoglobins: HbCO Cowtown (His HC3(146)beta----Leu), HbCO Wood (His FG4(97)beta----Leu) and HbCO Malmo (His FG4(97)beta----Gln). Our results show that the resonance assigned by Russu et al. to His HC3(146)beta in fact belongs to His FG4(97)beta. Although in Hb the pKa of His HC3(146)beta is 8.05 +/- 0.05 independent of ionic strength, in HbCO its pKa drops sharply with diminishing ionic strength, so that in the buffer employed by Russu et al. it has a pKa of 6.2 and makes a contribution to the alkaline Bohr effect that is 57% larger than in the phosphate buffer employed by Kilmartin et al. (1973). In HbCO A, His FG4(97)beta does not contribute to the Bohr effect, but in HbCO from which His HC3(146)beta has been cleaved (HbCO des-His), His FG4(97)beta is in equilibrium between two conformations with different pKa values. This equilibrium varies with ionic strength and pH, and presumably also with degree of ligation of the haem moiety. In HbCO A, His FG4(97)beta has a pKa of 7.8 compared to the pKa value of about 6.6 characteristic of free histidines at the surface of proteins. This high pKa is accounted for by its interaction with the negative pole at the C terminus of helices F and FG. It corresponds to a free energy change of the same order as that observed in the interaction of histidines with carboxylate ions and confirms the strongly dipolar character of alpha-helices, which manifests itself even when they lie on the surface of the protein. PMID- 4020867 TI - Molecular evolution of the seed storage proteins of barley, rye and wheat. AB - The major storage proteins (prolamins) of barley, rye and wheat are characterized by the presence of two or more unrelated structural domains, one of which contains repeated sequences. Because of this repetitive structure and their restricted distribution (only in grasses), it has been suggested that the prolamins are of recent origin. Contrary to this hypothesis, we show that parts of the non-repetitive domain of one group of prolamins are homologous with sequences present in a large group of seed proteins from monocotyledonous and dicotyledonous plants; including Bowman-Birk protease inhibitors, cereal inhibitors of alpha-amylase and trypsin, and 2 S globulin storage proteins of castor bean and oil seed rape. This implies an ancient origin for these non repetitive domains. The origins of the repetitive domains are not known but may lie within the grasses. PMID- 4020868 TI - Preliminary X-ray study of p-cresol methylhydroxylase (flavocytochrome c) from Pseudomonas putida N.C.I.B. 9869. AB - Single crystals of p-cresol methylhydroxylase, a flavocytochrome c from Pseudomonas putida, have been prepared. The crystals are orthorhombic, space group P212121 with unit cell parameters; a = 140.3 A, b = 130.6 A and c = 74.1 A. They contain a single non-symmetric dimer per asymmetric unit and diffract to at least 2.5 A resolution. PMID- 4020869 TI - Sequence analysis of mutations that affect the synthesis, assembly and enzymatic activity of the unc-54 myosin heavy chain of Caenorhabditis elegans. AB - We have sequenced 11 representative mutations of the unc-54 myosin heavy chain gene of Caenorhabditis elegans that affect the synthesis, assembly or enzymatic activity of the encoded myosin heavy chain. Six of the sequenced unc-54 mutations cause premature termination of protein synthesis. Four mutations (e1092, e1115, e1213, e1328) were ochre mutations, one mutation (e903) was a frameshift, which caused premature termination at a nearby UGA terminator, and one mutation (e190) was a deletion that altered the reading frame and caused termination at an ochre codon. Two mutations (e675 and s291) were inphase deletions, which resulted in a shortened myosin rod segment. These aberrant myosins fail to assemble into normal thick filaments. The sequence alterations of the missense mutations (e1152, s74, s95) indicated amino acid residues that are critical for myosin function. The mutation e1152 causes the production of a myosin heavy chain that fails to assemble into thick filaments. It had two adjacent amino acid substitutions at the extreme amino terminus of the rod, indicating a role for subfragment-2 in thick filament assembly. Mutants homozygous for s74 or s95 are very slow-moving, although they make myosin heavy chains that assemble normally. The encoded amino acid substitutions of s95 and s74 are in the 23 X 10(3) Mr and 50 X 10(3) Mr domains of the myosin head, flanking the ATP binding site. The sequenced mutations are distributed throughout the gene in the order predicted from genetic fine-structure mapping experiments. Seven of eight point mutations isolated following ethylmethane sulphonate mutagenesis were G X C to A X T transitions. A single X-ray-induced allele proved to be a deletion of two adjacent thymidine residues. The three deletion mutations were found in a region of the myosin rod with numerous direct and inverted nucleotide sequence repeats, but their origin cannot be accounted for by homologous recombination. Instead, a comparison of the deletion junctions suggests that the deletions arose by a site-specific mechanism. PMID- 4020870 TI - X-ray diffraction studies of 14-filament models of deoxygenated sickle cell hemoglobin fibers. Models based on electron micrograph reconstructions. AB - The transforms of a large number of models of deoxygenated sickle hemoglobin fibers, related to that derived from image reconstruction of electron micrographs, have been calculated and compared with X-ray diffraction data of 15 A resolution. The model of the fiber, determined from the reconstructed image, is a helix consisting of 14 filaments that associate in a specific mode to form seven pairs, or protofilaments. Pairs were identified through the pattern of filament loss in partially disassembled fibers and by the separation between molecules, in adjacent filaments, of half a molecular diameter, along the fiber axis. An alternative mode of filament association can be derived also from the surface lattice of the reconstruction, which meets these criteria for the pairing of molecular filaments. Both pairing modes have been used in the search for structures whose transforms show the best agreement with the diffraction data. Models were generated by the systematic translation of six protofilaments, taken in symmetry related pairs, in steps of 3.5 A along the fiber axis relative to a fixed central protofilament. Each translation of a protofilament corresponds to a different fiber model, whose transform was compared with observed data. In all, over 11,000 transforms were calculated. Of all the models considered, three have been found whose residuals are minimal. At 30 A resolution, similar to that of electron micrographs, the model derived from image reconstruction and the three found through our search procedure are indistinguishable. At 15 A, however, the transforms of these models show better agreement with the observed data than the transform of the reconstructed image. Comparison of residuals shows that the model derived from the reconstructed image can be rejected with 99.5% probability relative to the model, with the same pairing scheme, found by our search procedures. The two other models, derived from the alternative pairing scheme, are also more credible than the reconstructed image, but at a lower confidence level. Each of our three models is equally acceptable. Their existence may reflect structural polymorphism of the fiber. PMID- 4020871 TI - Molecular conformation of alpha-bungarotoxin as studied by nuclear magnetic resonance and circular dichroism. AB - We have examined the circular dichroism and nuclear magnetic resonance spectra of a long neurotoxin, alpha-bungarotoxin, over a wide range of pH values and temperatures, and under high salt conditions. The observations are interpreted partly in terms of the known crystal structure of this polypeptide. We support earlier findings of a greater degree of beta-sheet structure in solution than has been reported by X-ray crystallography and, importantly, the invariant residue associated with neurotoxicity, Trp29, is shown to be in a similar environment to that found in alpha-cobratoxin and LS III from Laticauda semifasciata. The implications of this observation for structure/function relationships are outlined. PMID- 4020872 TI - Kinetics of sickle hemoglobin polymerization. I. Studies using temperature-jump and laser photolysis techniques. AB - Using a combination of laser photolysis and temperature-jump techniques, the kinetics of hemoglobin S polymerization have been studied over a wide range of delay times (10(-3) to 10(5)s), concentrations (0.2 to 0.4 g/cm3) and temperatures (5 to 50 degrees C). A slow temperature-jump technique was used to induce polymerization in samples with delay times between 10(2) seconds and 10(5) seconds by heating a solution of completely deoxygenated hemoglobin S. For samples with shorter delay times, polymerization was induced by photodissociating the carbon monoxide complex in small volumes (10(-9) cm3) using a microspectrophotometer equipped with a cw argon ion laser. The photolysis technique is described in some detail because of its importance in studying hemoglobin S polymerization at physiological concentrations and temperatures. In order, to establish conditions for complete photodissociation with minimal laser heating, a series of control experiments on normal human hemoglobin was performed and theoretically modeled. The concentration dependence of the tenth time is found to decrease with increasing hemoglobin S concentration. In the range 0.2 to 0.3 g/cm3, the tenth time varies as the 36th power of the hemoglobin S concentration, while in the range 0.3 to 0.4 g/cm3 it decreases to 16th power. As the tenth times become shorter, the progress curves broaden, with the onset of polymerization becoming less abrupt. For tenth times greater than about 30 seconds, measurements with the laser photolysis technique on small volumes yield highly irreproducible tenth times, but superimposable progress curves, indicating stochastic behavior. The initial part of the progress curves from both temperature-jump and laser photolysis experiments is well fit with an equation for the concentration of polymerized monomer, delta (t) = A[cosh (Bt) -1], which results from integration of the linearized rate equations for the double nucleation mechanism described in the accompanying paper (Ferrone et al., 1985). The dependence of the parameters A and B on temperature and concentration is obtained from fitting over 300 progress curves. The rate B has a large concentration dependence, varying at 25 degrees C from about 10(-4) S-1 at 0.2 g/cm3 to about 100 s-1 at 0.4 g/cm3. PMID- 4020873 TI - Kinetics of sickle hemoglobin polymerization. II. A double nucleation mechanism. AB - A double nucleation mechanism for the polymerization of sickle hemoglobin is described. The mechanism accounts for all of the major kinetic observations: the appearance of a delay, the high concentration dependence of the delay time, and the stochastic behavior of slowly polymerizing samples in small volumes. The mechanism postulates that there are two pathways for polymer formation: polymerization is initiated by homogeneous nucleation in the solution phase, followed by nucleation of additional polymers on the surface of existing ones. This second pathway is called heterogeneous nucleation. Since the surface of polymers is continuously increasing with time, heterogeneous nucleation provides a mechanism for the extreme autocatalysis that is manifested as an apparent delay in the kinetic progress curves. In this mechanism, each spherulitic domain of polymers is considered to be initiated by a single homogeneous nucleation event. The mechanism explains the irreproducibility of the delay time for single domain formation as arising from stochastic fluctuations in the time at which the homogeneous nucleus for the first polymer is formed. Integration of the linearized rate equations that describe this model results in a simple kinetic form: A[cosh(Bt)-1] (Bishop & Ferrone, 1984). In the accompanying paper (Ferrone et al., 1985) it was shown that the initial 10 to 15% of progress curves, with delay times varying from a few milliseconds to over 10(5) seconds, is well fit by this equation. In this paper, we present an approximate statistical thermodynamic treatment of the equilibrium nucleation processes that shows how the nucleus sizes and nucleation equilibrium constants depend on monomer concentration. The equilibrium model results in expressions for B and B2A as a function of monomer concentration in terms of five adjustable parameters: the bimolecular addition rate of a monomer to the growing aggregate, the fraction of polymerized monomers that serve as heterogeneous nucleation sites, the free energy of intermolecular bonding within the polymer, and two parameters that describe the free energy change as a function of size for the bonding of the heterogeneous nucleus to a polymer surface. This model provides an excellent fit to the data for B and B2A as a function of concentration using physically reasonable parameters. The model also correctly predicts the time regime in which stochastic behavior is observed for polymerization in small volumes. PMID- 4020874 TI - A plasmodial alpha-tubulin cDNA from Physarum polycephalum. Nucleotide sequence and comparative analysis. AB - As the first step towards correlating structure and function of tubulin in the slime mold Physarum polycephalum we have elucidated the nucleotide sequence of a cDNA that appears to code for all but the last 25 to 30 C-terminal amino acids of a plasmodial alpha-tubulin. Differences in amino acid sequence from those of other alpha-tubulins are distributed fairly evenly throughout the sequence, although a relatively extensive conserved region is found in position 396 to 426 near the C terminus. A small region in position 298 to 307 contains a cluster of amino acid residues unique to Physarum alpha-tubulin. The sequence is 70% homologous to two yeast alpha-tubulins and about 83% homologous to five animal alpha-tubulins. A comparison of the homologies of all the known alpha-tubulins indicates that a large decrease in the accepted point mutation rate has occurred during the evolution of the metazoa, suggesting a major functional specialization of microtubules. PMID- 4020876 TI - Essential contribution of thrombocytes to the occurrence of catecholamine-induced cardiac necroses. AB - The role of thrombocytes in the production of isoproterenol-induced cardiac necrosis was investigated in rats rendered thrombocytopenic (A) as well as in rats treated with a prostacyclin analogue (B). According to quantitative morphometric evaluation the area of necrotic tissue amounted to about 1% 9 h following administration of isoproterenol (40 mg/kg). In both groups of treated animals the number and area of necroses were strongly reduced (to 23% group A, to 34% group B, P less than or equal to 0.1 for both groups). In contrast, the reduction of myocardial adenine nucleotide levels induced by isoproterenol was the same (5.06 to 3.57 and 3.60 microM/g wet wt, respectively) in thrombocytopenic and non-thrombocytopenic rats. Quantitative comparison of the fraction of necrotic tissue and of the fraction of lost nucleotides suggests that non-necrotic rather than necrotic tissue predominantly contributes to the reduction of nucleotides. The dependence of cardiac necrosis production on the presence or normal aggregability of platelets points out at platelet-dependent microvascular alterations as a main cause of isoproterenol-induced cardiac necroses. PMID- 4020875 TI - Catecholamine-induced myocardial cell damage: catecholamines or adrenochrome. AB - Recent evidence suggests that catecholamine-induced myocardial damage may be due to the cardiotoxic property of its non-physiological metabolite, adrenochrome. We investigated whether catecholamine-mediated myocardial damage is the result of catecholamine stimulation per se or the consequence of physiological or non physiological metabolites. In the Langendorff perfused rat heart, fresh epinephrine (10(-6) M) solution increased cumulative lactate dehydrogenase (LDH) release when the perfusion pressure was 100 cm but not 65 cm, 3640 +/- 665 v. control 545 +/- 45 mIU/g/35 min respectively (P less than 0.01). In the left atrial perfused rat heart working against a hydrostatic pressure of 100 cm, fresh epinephrine (10(-6) M) solution produced the greatest increase in cumulative LDH release, 9346 +/- 1806 v. control 472 +/- 47 mIU/g/45 min respectively (P less than 0.01). Beta 1 but not alpha 1 adrenergic stimulation provoked enzyme leakage. Beta-adrenoceptor antagonism with atenolol 10(-5) M prevented catecholamine-induced leakage. Physiological metabolites of epinephrine viz metanephrine 10(-6) M, dihydroxymandelic acid 10(-6) M, vanillylmandelic acid 10( 6) M, and the non-physiological metabolite adrenochrome 10(-6) M to 10(-4) M did not increase the cumulative LDH release over 45 min. When adrenochrome 10(-4) M was perfused for 120 min enzyme release occurred, albeit only a third of that induced by epinephrine 10(-6) M over 45 min. We demonstrate that epinephrine induced myocardial cellular damage is due to the direct effect of catecholamine stimulation acting on the beta-adrenergic receptor. The amount of left ventricular work appears to determine the extent of cellular damage. Physiological metabolites and the non-physiological metabolite, adrenochrome are not responsible for catecholamine-induced myocardial cellular damage. Epinephrine 10(-6) M caused a positive inotropic effect, whereas adrenochrome 10(-4) M induced contractile failure. Contractile failure was due to a negative inotropic effect and coronary artery vasoconstriction. Adrenochrome induces myocardial cellular damage and contractile failure but only in a concentration of 10(-4) M, this concentration does not appear to have pathophysiological relevance. PMID- 4020877 TI - Adaptive changes in subcellular calcium transport during catecholamine-induced cardiomyopathy. AB - Rats were injected intraperitoneally with isoproterenol in dosage of 40 mg/kg body weight and heart microsomal and mitochondrial fractions were isolated 3, 9 and 24 h later. The heart/body weight ratio increased at 9 and 24 h after injection without any changes in the yield of subcellular organelles. Microsomal calcium uptake was significantly elevated at 3 h but returned to normal at 9 h and then became depressed 24 h post-injection. Mitochondrial calcium uptake was significantly increased 9 and 24 h after isoproterenol administration. Kinetic parameters of the calcium transport function indicated that the apparent affinity for Ca2+ remained unchanged, whereas Vmax values were altered in the experimental groups. Although there was no significant change in the phospholipid composition, the total phospholipid contents were increased (at 3, 9 and 24 h for microsomes; 3 and 9 h for mitochondria) in both types of organelles. The protein composition, as determined by gel electrophoresis, was altered in microsomes, but not in mitochondria. These results demonstrate rapid structural and functional changes in subcellular organelles. Such alterations may play an adaptive role in maintaining the intracellular calcium homeostasis during the development of catecholamine-induced cardiomyopathy. PMID- 4020878 TI - Functional and morphological organization of the guinea-pig sinoatrial node compared with the rabbit sinoatrial node. AB - The primary pacemaker, i.e. the group of pacemaker cells discharging the sinoatrial node comprises less than 1000 cells in the guinea-pig and about 5000 cells in the rabbit. These primary pacemaker cells are described as 'central nodal' cells in light microscopy and as 'typical nodal' cells in electron microscopy. The action potential of the leading cells has a higher upstroke velocity in the guinea-pig than in the rabbit (6.2 v. 1.9 V/s). Gap junctions have been observed even in the very center of the node in both species. A zone of double-component action potentials at the septal margin of the node was observed in the rabbit, but not in the guinea-pig. Evidence is presented for abrupt transitions in electrophysiological as well as in ultrastructural characteristics in the guinea-pig sinoatrial node. The differences in intrinsic cycle length between both species but also between individuals of the same species are discussed. PMID- 4020879 TI - Alterations to potassium fluxes in the heart during chronic dietary potassium depletion. AB - Dietary K+ depletion in rabbits causes a loss of cellular K+ from skeletal muscle but not from cardiac muscle, and it has been suggested that this is due to a specific protective mechanism in the heart. Net uptake and efflux of 42K was investigated in the interventricular septum of the rabbit. Acute reductions in extracellular [K+] caused a loss of K+ from tissue of both normal and K+ depleted animals. In the K+ depleted group the relationship between [K+]e and net uptake was altered, so that the maximum rate of uptake was increased, and this was obtained at a lower [K+]e. There were no significant changes in K+ efflux. These results would be consistent with an adaptive change to the cardiac cell Na+ pump during chronic K+ depletion. PMID- 4020880 TI - Comparative morphometry of the mitochondria and activity of some enzymes in the myocardium of small mammals. AB - Heart rate in mammals is inversely related to body weight. In the etruscan shrew it exceeds 960 beats/min. Since the heart depends primarily on energy from aerobic sources, it was interesting to examine some morphological parameters of the mitochondria in some mammals with a high heart frequency. Volume fraction and surface to volume ratio of the mitochondria in the myocardium were determined in the white rat (221 g), white mouse (36 g), white-toothed shrew (8 g) and the etruscan shrew (2 g) using morphometric methods. The volume fraction and surface to volume ratio of the mitochondria increased progressively and significantly as body weight of the animal decreased. The increase was higher in the surface to volume ratio than in the volume fraction. It reached a value which was 62% higher in the etruscan shrew than that of the white rat, while in the volume fraction of the mitochondria the maximal increase was only 34%. In accordance with the morphometric data, enzymatic activity of succinic dehydrogenase in the myocardium was inversely related to body weight. Creatine phosphokinase activity revealed a similar but not statistically significant trend. Lactic dehydrogenase activity was about three-fold higher in the white rat than in the white toothed shrew. It is concluded that one of the adaptive responses of the heart in small sized mammals to increase ATP production is not only elevation of the volume fraction of the mitochondria, but also an increase of their surface to volume ratio to provide a higher rate of oxygen diffusion to them. PMID- 4020881 TI - Experimental catecholamine-induced myocardial necrosis. II. Temporal development of isoproterenol-induced contraction band lesions correlated with ECG, hemodynamic and biochemical changes. AB - Catecholamines have been shown to produce irreversible contraction band lesions of myocardial cells. However, little is known about the temporal appearance and correlation of the acute form of coagulative myocytolysis with ECG, hemodynamic and biochemical parameters. Groups of adult mongrel dogs were anesthetized with sodium pentobarbital, infused continuously with isoproterenol (2.5 micrograms/kg/min) and killed after periods of 0, 5, 15, 30, or 60 min. There were two predominant myocardial patterns: 'paradiscal' and 'holocytic' contraction band lesions. Either type of lesion was non-existent or rare in the control hearts. The small 'paradiscal' contraction band lesions were present as early as 5 min of isoproterenol infusion, particularly in the inner myocardial layer. The large 'holocytic' contraction band lesions were present by 15 min, however, they were not produced in any significant numbers before 30 min. Both types of contraction band lesions continued to accumulate up to 60 min. ST segment depression was the predominant ECG change. This occurred as early as 5 min when heart rate, blood pressure and dP/dt values had also significantly changed. The high-energy phosphates, phosphocreatine and ATP, started declining as early as 5 min. Furthermore, these phosphates and lactate were distributed in transmural gradients across the left ventricular wall with the greatest change in the endocardial third. This was also the site of the largest accumulation of each type of contraction band lesion. While the lesions correlated with certain biochemical and hemodynamic changes, the underlying pathophysiology is more complex than ischemia or high-energy phosphate depletion alone. PMID- 4020882 TI - Involvement of hydrogen peroxide and hydroxyl radical in the 'oxygen paradox': reduction of creatine kinase release by catalase, allopurinol or deferoxamine, but not by superoxide dismutase. AB - The objective of this study was to test the hypothesis that cytotoxic oxygen metabolites participate in lytic cardiac cell damage, detected as creatine kinase release, upon reoxygenation of hypoxic, isolated buffer-perfused hearts (oxygen paradox). Perfusate additives included: superoxide dismutase (30 mg/l); catalase (2 mg/l); deferoxamine (0.5 mM); and allopurinol (1 mM). Creatine kinase release upon reoxygenation was reduced, to levels not significantly different from nonhypoxic controls, by adding either catalase, allopurinol or deferoxamine to the buffer during hypoxia. Reduced creatine kinase leakage was not accompanied by parallel preservation of ventricular function or coronary vascular resistance. Administration of catalase during hypoxia was superior to administering it only during reoxygenation. Treatment with catalase during both hypoxia and reoxygenation provided no more protection than administration only during hypoxia. The data suggest that an important component of hypoxia-induced cardiac cell damage is due primarily to hydrogen peroxide, which may then form hydroxyl radical. Superoxide anion plays an important role as a precursor of these species, but added superoxide dismutase alone did not significantly reduce creatine kinase loss. The data also suggest that damage resulting in creatine kinase release upon reoxygenation occurs during oxygen deprivation, and it is mediated in part by cytotoxic oxygen metabolites. PMID- 4020883 TI - Studies on cumene hydroperoxide-induced lipid peroxidation in the isolated perfused rat heart. AB - In the isolated, perfused rat heart, lipid peroxidation, induced by cumene hydroperoxide (Cum OOH), is accompanied by the release of malondialdehyde (MDA). Using a modified perfusion technique resulting in the separate collection of coronary and interstitial effluent, it can be shown that upon Cum OOH (0.5 mM) perfusion there is an immediate release of MDA in the coronary effluent and a delayed release in the interstitial fluid, indicating the susceptibility and coronary vascular tissue towards free radical-induced lipid peroxidation. Perfusion with Cum OOH leads to an initial increase of the coronary flow and a depressed contractility followed by a cardiac arrest concomitantly with the onset of MDA release in the interstitial fluid. Finally, during prolonged perfusion the coronary flow diminishes and contracture of the heart muscle ('stone heart') develops. These phenomena resemble those occurring during the 'calcium paradox'. Although the contractility diminishes immediately after the perfusion with Cum OOH the tissue ATP level and energy charge (formula; see text) remain constant. From the moment of cardiac arrest the ATP and creatine phosphate levels gradually decrease and the energy charge drops simultaneously with the appearance of MDA in the interstitial fluid. In contrast to the calcium paradox there is no simultaneous increase in the myocardial AMP level. Various mitochondrial enzymes (cytochrome c oxidase, monoamine oxidase, carnitinepalmitoyltransferase I and palmitoyl CoA synthetase) were tested and not affected by Cum OOH perfusion. During the development of contracture after 20 min of Cum OOH perfusion massive contraction band necrosis of cardiac tissue occurs. However, overall protein release is lower when compared with the protein release during the calcium paradox.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4020884 TI - The relative sensitization by acidosis of five calcium blockers in cat papillary muscles. AB - We have previously reported that the negative inotropic effects of both verapamil and nifedipine on cat papillary muscles are enhanced as pH is lowered from 7.4 to 6.8 and 6.0. These studies have now been extended to compare the relative sensitization by acidosis of verapamil, nifedipine, lidoflazine, perhexilene and diltiazem. Developed tension was recorded in cat papillary muscles and the calcium concentration was adjusted over the range 2 to 10 mM. At pH 7.4, addition of all five drugs moved the dose response curve to the right with pA2 values from 4.82 (lidoflazine) to 9.94 (nifedipine). At pH 6.0, there was eight-fold sensitization by acidosis for verapamil, but four, three, and two-fold sensitization for nifedipine, lidoflazine and perhexilene. Diltiazem, however, was not sensitized by acidosis. The differential effects of acidosis on the negative inotropic properties of the five drugs may reflect their ancillary properties opposite gating of the calcium channel, local anaesthesia, intracellular calcium movement or Na+/Ca2+ exchange, but also suggest that diltiazem may have the property of inhibiting the effects of low pH on cell membranes. PMID- 4020885 TI - Ventricular fibrillation and the Brattleboro rat. AB - Despite considerable evidence from both clinical and animal experiments, the role of beta-adrenergic stimulation in the development of life-threatening cardiac arrhythmias is not well understood. Recent studies indicate that the posterior pituitary hormone, arginine vasopressin, may have a modulatory effect on cardiovascular sympathetic tone, especially with respect to blood pressure and heart rate. Employing the homozygous Brattleboro rat, an animal genetically deficient in the synthesis of arginine vasopressin, the following report offers evidence that the neuropeptide may also act on central pathways to suppress arrhythmogenic activity elicited by beta-adrenoceptor stimulation. PMID- 4020887 TI - Organizational structure and function. PMID- 4020886 TI - Enhancement of aortic blood flow with a linear anionic macropolymer of extraordinary molecular length. AB - The addition of small amounts of high mol. wt polymers to a fluid moving through a pipe typically increases fluid viscosity and thereby diminishes the rate of flow. Under appropriate conditions of flow, however, the addition of linear polymers of high mol. wt--of the order of 10(5) to 10(7) daltons--may cause the flow to increase as much as 3-fold and occasionally more without altering the driving pressure. This effect, generally known to hydrodynamicists under the rubric 'Toms phenomenon' or as 'polymer drag reduction', generally occurs at high (greater than 1000) Reynolds numbers. However, flow also increases at much lower Reynolds numbers under certain conditions, including oscillatory, pulsatile, and helicoidal flows and flow through a column of sand. The Toms phenomenon has been repeatedly observed in various types of flow with both aqueous and organic solvents in combination with a wide variety of polymer additives. A marked fall in the pressure gradients of constant blood flows through pipes has also been observed upon the addition of polyacrylamide, poly(ethylene oxide), deoxyribonucleic acid, or a polysaccharide extracted from okra. It is the consensus among students of fluid mechanics that linear macromolecules suppress flow disturbances by stabilizing or laminizing the dynamic fluid structure when rod- or thread-like particles align themselves parallel to the axis of flow. Mostardi et al. demonstrated with hot film anemometry that aortic flow instabilities downstream from a temporary partial occlusion are dampened after infusion of a polymer drag-reducing agent, Separan AP-30 (Dow Chemical Co.).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4020888 TI - Black adolescents: issues critical to their survival. PMID- 4020890 TI - Effects of a summer preview program of study skills and basic science topics on the academic performance of minority students. AB - A summer preview program was designed to enhance the academic performance of minority students in medical school. In the five-week program the students met from 8:00 AM to noon, five days a week. The two components of the program were study skills and selected basic science topics deemed critical for success in the first year.This paper is an analysis of three years (1980 to 1982 inclusive) of the program. Only three of the 14 participating minority students failed to complete the requirements of the first year of the curriculum. In contrast, nine of the 11 nonparticipating minority students did not complete the requirements for the first year. The conclusion is that the program can enhance the academic performance of minority students in the first year of the medical school curriculum. PMID- 4020889 TI - Increased MB-creatine kinase isoenzymes in an alcoholic population. AB - Using agarose gel electrophoresis MB-creatine kinase (MB-CK) activity was examined in the serum of 120 patients with acute alcohol intoxication admitted to a detoxification ward. Total CK activity was increased in 67 percent of patients and MB-CK activity was increased in 8.3 percent. Alcoholic patients also were studied by Sephadex chromatography and, in seven cases, MB-CK was greater than three standard deviations from the normal. Thus, this study demonstrates that acute alcohol intoxication is associated with increased MB-CK activity. These findings raise the possibility that excessive alcohol ingestion may lead to acute myocardial injury. PMID- 4020891 TI - Clinical pharmacokinetics: a simplified approach, Part 1. AB - Clinicians often find that the application of pharmacokinetic principles for the calculation of a drug regimen is bewildering and difficult. In this article it is shown that clinically useful calculations can be simply done at the bedside using a handheld calculator. The only requirement is an understanding of the terms that define the pharmacokinetic behavior of a drug. Appropriate manipulation of these terms will allow calculation of loading and maintenance doses, peak and average plasma concentrations, and other useful pharmacological data. The result will be improvement in drug therapy. PMID- 4020892 TI - Health care: development of data for a marketing approach. AB - Marketing in health care is a relatively new process. It is a business tool that can serve a very useful purpose. Health care management has become aware of the usefulness of marketing in long-range planning. Through a well-thought-out marketing plan, the provider will not be leaving the future to chance. A well conceived, patient-oriented, competitor-aware marketing plan should place the medical practice at a strategic advantage as the health care industry joins other industries in the competitive marketplace for the consumer's dollar.The ever increasing political and regulatory environment that the health care field is undergoing emphasizes the need for the inclusion of marketing skills, such as cost containment, in the medical curriculum. It should be the obligation of the training facilities as well as medical societies to respond to this need by providing the education that will enable black providers to survive in this competitive environment. PMID- 4020893 TI - The origin of psychosomatic disorders in parent-adolescent relationships. AB - This paper explores the impact of parent-adolescent relationships in the development of psychosomatic disorders. It briefly reviews the intra-family psychosocial pathogenesis of these disorders and suggests preventive approaches. PMID- 4020894 TI - Hamartoma. AB - The case of a patient with benign pulmonary hamartoma is presented. Examination of the lung by roentgenographic rays demonstrated the classical "popcorn calcification" in the lesion. PMID- 4020895 TI - Reactions of the geniculate cells to extraocular proprioceptive activation in rabbits. AB - The aim of these investigations was to advance our knowledge of the influence of extrinsic ocular muscle (EOM) stretching on cell excitability of the retinocortical pathway. The initial goal was the lateral geniculate; however, histologic analysis indicated that most cells that responded to stretching were located near its superior edge, in an area analogous to the perigeniculate. Rabbits were anaesthetized and prepared for single-cell recordings. The extraocular muscles were detached from the eye and attached to a rigid tungsten hook. The hook was soldered to the pivot of a galvanometer that was controlled by a waveform generator. Precise and repeated length changes were obtained with extension and relaxation ramps of constant velocity. Thirty percent of the units (N = 250) responded to EOM stretching. These stimuli evoked either an excitation or a decrease of the units' spontaneous activity. Several experimental controls provided evidence that the signals that evoked the geniculate responses originated from proprioceptors belonging to the EOM. Most responding cells had their receptive fields located eccentrically (greater than or equal to 50 degrees). Also, cells that reacted to EOM stretching responded to optic nerve stimulation with a significantly shorter latency than cells that were unresponsive. Pairing the EOM stretching with light stimuli produced the following results. In about half of the units the light-evoked responses augmented, but in 28% of the cells the light-evoked discharges decreased. These effects were obtained even though EOM stretching delivered singly failed to elicit a reaction from the cell. Histologic reconstructions indicated that cells were distributed in a discrete region lying rostral and dorsomedial to the lateral geniculate nucleus. This area has been associated with the perigeniculate nucleus in cats and rats. PMID- 4020896 TI - Effects of corticosterone and 5 alpha-dihydrocorticosterone on brain excitability in the rat. AB - The effects of corticosterone (B) and its reduced metabolite 5 alpha dihydrocorticosterone (DHB) on CNS activity in the rat were examined. Two indices of brain excitability were evaluated: 1) amplitude of population responses (evoked potentials [EP] to sciatic nerve stimulation) and 2) changes in the rate of firing of tonically discharging neurons--both at pontine brainstem regions of the reticular formation. Experiments were carried out in adrenalectomized rats, and recordings were obtained from animals under urethane anesthesia. Steroids were dissolved in a 4:1 saline:Cremophor-El (Sigma) solution and doses of 750 micrograms/0.5 ml were injected (IV). The effects of B on EPs were bidirectional. Increases (8 animals) and decreases (6 animals) of the amplitude responses in different animals were observed. In 4 animals, no changes were detected. In contrast, injection of DHB produced a consistent and significant reduction of brainstem sciatic evoked potentials in 10 of 12 animals tested; 2 animals did not respond to the steroid. At the neuronal level, the effects of the steroids were evaluated by the changes they induced in the mean firing frequency (P less than 0.01) measured during 5-min intervals as determined by a one-way analysis of variance and analysis with a test of multiple comparisons. Only cells that fired in a stationary mode for 15 min before the steroid injection were studied. A more consistent pattern of responses to B was observed at the single-cell level. From 31 neurons that responded to the hormone, of 76 examined, 27 showed an increase in their firing rate and only 4 neurons showed a decrease. The increase in firing rate had an onset latency of 2-5 min (means = 3.5, SE 0.43) with a duration of 16 25 min (means = 17.5, SE 2.7). Of 69 neurons that were tested with DHB, 51 showed a significant decrease in their mean firing frequency. Onset latency of the effect was 2-8 min (means = 4.0, SE 1.21) and the duration of the induced changes was 16-40 min (means = 30.0, SE 3.47). Central interactions of DHB and B when sequentially administered were examined in 28 neurons. Of these, 21 responded to DHB administration with a significant decrease in their firing rates. In 11 of these neurons, injection of B, 5 min after DHB, was followed by a rapid (1-2 min) return of the neurons to baseline firing rates.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 4020897 TI - Excitatory effect of amino acids on identified neuron R14 of Aplysia. I. Glycine induced depolarization and its ionic mechanism. AB - The ionic mechanism of the membrane effect of glycine on identified neuron R14 of Aplysia was investigated with conventional intracellular recording and voltage clamp techniques. Both localized and bath applications of glycine markedly depolarize R14. Bath-applied glycine induced an inward current that gradually reached a maximum and remained at that level until glycine was washed out. Displacement of the holding potential from -46 to -121 mV increased the inward current. The extrapolated reversal potential was +38.6 mV. Reduction of [Na+]o reversibly decreased the inward current. Alterations of [K+]O, [Cl-]O, and [Ca2+]O, as well as bath-applied ouabain and sodium cyanide, did not affect the inward current. These results suggest that glycine can induce an Na+ current and that the glycine-induced inward current does not reflect an active uptake by an Na+-coupled transport system of glycine into the neuron. PMID- 4020898 TI - Prenatal and postnatal hypothyroidism abolishes lesion-induced noradrenergic sprouting in the adult rat. AB - The effects of altered thyroid states on regeneration in the central nervous system are equivocal. This work was undertaken to examine the influence of propylthiouracil-induced (PTU-induced) pre- and postnatal hypothyroidism on collateral sprouting of noradrenergic (NA) axons in the habenula (Hb), following lesions in the stria medullaris (SM) of the adult rat. Ten pregnant dams were divided into control and PTU-treated groups. Control rats had free access to food and water and the hypothyroid group received, in addition, 0.05% (w/v) of PTU in their drinking water, beginning on day 12 of gestation and continuing post partum through lactation until the offspring were weaned at age 22 days. The pregnant dams received, in addition, daily injections of thyroxine (25 micrograms/kg, ip) and only male pups were used in the study. At weaning the pups were removed from the dams and placed in cages with free access to food and water. The hypothyroid offspring received 0.05% (w/v) PTU in the drinking water until sacrificed at 10 weeks of age. At 6 weeks, some rats in each group received bilateral lesions in the SM and the remainder were sham-operated. All rats were sacrificed 4 weeks after operation. Thus, four groups were formed: 1) control/sham, 2) control/lesion, 3) PTU/sham, 4) PTU/lesion. Sprouting of NA fibers in discrete regions of the Hb was identified by norepinephrine (NE) levels and by fluorescence histochemistry. Blood levels of thyroid stimulating hormone (TSH) were determined. The results show that pre- and postnatal induced chronic hypothyroidism abolished NA sprouting in the partially deafferented Hb. Furthermore, lesions of the SM resulted in a marked decrease in serum TSH levels. PMID- 4020899 TI - Thoracic dorsal funicular lesions affect the bouton patterns on, and diameters of, layer VB pyramidal cell somata in rat hindlimb cortex. AB - The effect of spinal dorsal funicular lesions (T 12) upon the frequency of boutons on, and diameters of the somata of pyramidal cells in layer VB of hindlimb cortex was studied. Adult rats sustained bilateral damage to either the dorsal column (DC, n = 10) alone or DC combined with the corticospinal tract (CS) (DC + CS, n = 34) and were utilized 1, 2, 3, 7, 14, 30, 45, 60, 90, or 120 days postoperatively (DPO). Neurons randomly sampled from 44 lesioned and 13 unoperated cases were analyzed for the number of silver-impregnated boutons (Rasmussen method) on the circumference of the soma as well as diameters of the soma, nucleus, and nucleolus. Analyses of variance comparing across lesioned and normal groups were significant for bouton counts on the soma (P less than 0.01), and diameters (long axis) of somata (P less than 0.01) and their nuclei (P less than 0.05). Both lesioned groups exhibited significant decreases from normal for these latter three parameters. With respect to survival time for the DC + CS lesioned animals we noted the following: (1) Bouton counts on the soma significantly decreased below normal between 1 and 60 DPO; this decrease was most dramatic during the first three days postlesion. (2) Somal diameter (long axis) significantly decreased below normal between 2 and 120 DPO (except at 14 and 90 DPO). (3) Nuclear diameter (long axis) significantly decreased below normal only at 90 DPO. (4) Bouton counts on somata of neurons in layers VB and IV [Ganchrow and Bernstein, 1981] of hindlimb cortex correlated negatively and significantly across 120 postlesion days. The rapid shrinkage and reduced afferentation of layer VB somata during the first week following DC + CS lesions suggest initial, retrograde reactions to CS axotomy. Since bouton counts on layer VB somata were significantly less (P less than 0.05) in DC- than DC + CS-lesioned rats, it is hypothesized that CS axotomy regulated a set-point for increased afferentation which was maintained on the shrunken somata between 7 and 120 DPO. PMID- 4020900 TI - Functional role of the potassium-induced stimulation of oxygen uptake in brain slices studied with cesium as a probe. AB - The potassium-induced stimulation of oxygen consumption in brain slices has a threshold value of 15-20 mM potassium, and it reaches its maximum at 35-50 mM. Although this phenomenon now has been known for almost 50 years, its physiological role remains undetermined. One reason for this may be that the high concentrations of potassium that are required for this response also have many other consequences, e.g., a depolarization of the cells, and that the different effects to some extent may mask each other. For this reason this investigation studied the effects of cesium, which evokes a maximal stimulation of oxygen consumption already at 15 mM. Like potassium, concentrations of cesium that stimulate oxygen consumption also lead to an enhanced swelling. Unlike potassium, the sodium content is affected very little by these concentrations of cesium, whereas cesium and chloride contents are increased. On this basis it is concluded that the cesium-induced stimulation of oxygen uptake is a metabolic manifestation of an active uptake of cesium and chloride, which secondarily leads to an uptake of water, i.e., the cesium-induced swelling. Analogously, it is suggested that the potassium-induced stimulation of oxygen uptake represents an active accumulation of potassium and chloride. PMID- 4020901 TI - Asymmetric molecular forms of acetylcholinesterase in mammalian skeletal muscles. AB - Velocity sedimentation analysis of acetylcholinesterase (AChE) molecular forms was performed separately in endplate-rich and endplate-free regions of the diaphragm muscle of the rat, guinea pig, rabbit, dog, and pig, and in mm. erectores trunci and m. vastus lateralis in man. Several high-ionic-strength media were first tested to achieve better solubilization of AChE from rat muscles than by the usual 1 M NaCl-Triton X-100 medium. Ninety-five percent of the AChE from the motor endplate region of the rat diaphragm was solubilized in a single extraction step by medium containing 1 M lithium chloride instead of NaCl. Homologous molecular forms of AChE were found in all species. The asymmetric forms were invariably present in the endplate regions of muscles but their activity in endplate-free regions was much lower than in endplate regions in all investigated mammals except in man. Essentially the same pattern of AChE molecular forms was present in both regions in human muscles. High extrajunctional activity of the asymmetric forms makes human muscles similar to immature rodent muscles in vivo and in culture. The pattern of AChE molecular forms in the endplate region of the diaphragm in senile 24-month-old rats was not significantly different from that in 3-month-old animals. The persistence of the asymmetric AChE forms in the diaphragm of senile rats suggests that neuromuscular interactions do not become deficient with age in this muscle. PMID- 4020902 TI - Separation of cephaloridine from the rat urine contaminated by feces and diet pellets in high-performance liquid chromatography. Pretreatment with strongly basic anion exchange resin following deproteinization. AB - In this study, a high-performance liquid chromatographic method including a treatment with ion exchange resin following a deproteinization treatment, was studied for determination of cephaloridine in the rat urine which was contaminated by pieces of feces and diet pellets. The solvent system used was 10% acetonitrile (v/v) in 0.1 M K2 HPO4-H3 PO4 buffer, pH 7.5, and this was isocratically eluted on a reversed-phase column of NOVA-PAK C18. The urine sample containing cephaloridine was deproteinized, treated with a strongly basic anion exchange resin of Dowex-1-Chloride, and then chromatographed. In comparison to the sample treated by the simple deproteinization, the residual substances after the deproteinization, which interfered the cephaloridine peak, were removed by the following treatment with Dowex-1-Chloride, as was confirmed using a three dimensional computing spectrophotometric monitor. Thus, the present method is considered to be useful in determination of cephaloridine in such body fluids as urine in which many interfering substances are contained. PMID- 4020903 TI - A preliminary study on long term toxicity test. Age-related alterations of bone marrow cellularity in Sprague-Dawley and Wistar rats. AB - Age-related alterations in bone marrow cellularity were examined on SD and Wistar SPF rats. Six rats/strain/sex were sacrificed at 58, 83, 109 and 123 or 135 weeks of age and quantitative assessment and categorization of the bone marrow cells were performed. One male and two female SD rats suffering from leukemia were excluded from statistics. Age-related increases of myeloblasts and plasma cells were observed in rats of either strain and either sex. Age-related decreases in percentages of lymphocytes were noticed in SD, but not in Wistar rats. Age related alterations in absolute numbers of marrow lymphocytes were equivocal in either strain. PMID- 4020904 TI - Lipid peroxidation in human paraquat poisoning. AB - The concentration of malondialdehyde (MDA) in tissues in paraquat poisoning was compared between humans and rats. Lung MDA increased in humans, but not in rats despite of development of histological change of the lung. On the other hand, liver MDA increased both in humans and in rats. These findings suggest that lipid peroxidation may not be primary mechanism of paraquat toxicity. PMID- 4020905 TI - [Long-term toxicological studies with mizoribine (Bredinin) in beagle dogs (the first report). Blood chemistries, pharmacokinetics of mizoribine and fertility studies of the male dogs]. AB - For long-term toxicological studies, mizoribine at the dose of 2.5 mg/kg body weight was administered orally to two male and two female Beagle dogs for 36 consecutive months, once a day, 6 days a week, with a day-off on the 7th of each week. As a control group, 2 male and 2 female dogs were kept under the same conditions as the treated group. The above experiment resulted in no abnormal general symptoms being found in either group. In addition, body weight gain instead of weight loss was observed in both groups. Moreover, hematological and biological parameters were in the normal range, and no statistical difference was obtained between the two groups. An additional 10 mg/kg of mizoribine was administered once to both groups at the months of 6, 12, 18, 24, or 36 after the onset of this toxicological study so as to determine the pharmacokinetic behavior of serum mizoribine. This resulted in no significant difference being observed between the two groups. Therefore, it can be inferred that accumulation of mizoribine is not induced by its long-term repeated administration. In fertility study, the analysis of the sperm and the mating ability of a male dog with an appropriate healthy female dog revealed that mizoribine at this dose did not provoke any abnormalities in male gonadal functions. PMID- 4020906 TI - [Long-term toxicological studies with mizoribine (Bredinin) in beagle dogs (the second report). Pathological studies on visceral organs]. AB - Four Beagle dogs were administrated with mizoribine 2.5 mg/kg/day for 36 months. Clinical and laboratory findings were fully described in the first report, in which no remarkable abnormalities were detected. Visceral organs of the experimental group and non-treated control group were submitted for pathological investigations. No conspicuous macroscopical and microscopical drug-induced changes were disclosed in the experimental group. PMID- 4020907 TI - Patterns of trauma care costs and reimbursements: the burden of uninsured motorists. AB - In today's rapidly changing medical-economic environment, hospitals must continually reexamine their services to determine which are cost efficient. We used a database system to analyze our financial experience with motor vehicle accident victims discharged between July 1982 and June 1983. We found that motor vehicle accidents accounted for 2.1% of discharges, but 6.6% of patient-days. The average length of stay was 23.8 days, more than three times the hospital average (7.4 days). Charges averaged +723 per day, essentially identical with the hospital average. In terms of patient-days, 51% of accident victims were covered by private insurance, 39% by Medi-Cal (California's Medicaid), and 3% by Medicare; 7% were uninsured and unsponsored. Hospital charges related directly to patient-days and were identical for the four financial categories. Overall reimbursement for these patients was 80.3% of charges, approximately equal to our estimated costs. Reimbursement as a percentage of charges varied greatly according to the category of sponsorship: private insurance, 90%; Medicare, 78%; and unsponsored, 15%. Medi-Cal paid a fixed confidential per diem rate. CONCLUSIONS: Caring for victims of motor vehicle accidents was a break-even proposition for our institution in 1982-1983. Uninsured and unsponsored patients produced a large deficit which of necessity had to be made up by cost shifting to privately insured patients or by direct tax subsidies. Motor vehicle insurance per se made only a modest contribution to our reimbursement for the care of these patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4020908 TI - The economics of fatal injury: dollars and sense. AB - This study reviewed the direct costs (charges for goods and services) for 77 consecutive patients who presented to this trauma service with a Trauma Score (TS) of four or less. Seventy-four patients died (96.1%). The survival rates based upon the Trauma Scores were: TS 1, 0(0/34); TS 2, 0(0/9); TS 3, 7.7% (1/13); TS 4, 9.5% (2/21). Only four nonsurvivors lived more than 24 hours. The remaining 70 patients died within 24 hours without achieving even transient cardiovascular stability. Three of the 77 patients survived (3.9%) but only one achieved a productive recovery. The total direct cost for the 77 patients was +544,477.66. Physician fees, which accounted for 26.7% of the direct costs, averaged +1,887.57 per patient (range, 0-+11,291.00). The average direct cost for the three survivors was +50,138.94. The average direct cost for nonsurvivors was +5,325.18 (+3,383.29 for patients with a TS 1 or 2, +8,018.76 for patients with a TS 3 or 4). The hospital direct costs for nonsurvivors ranged from +40.00 for a patient declared dead on arrival to +57,817.91 for a patient who died 41 days after admission. It is futile to continue resuscitational efforts if a valid Trauma Score of 1 or 2 is confirmed shortly after the initiation of appropriate resuscitative measures. Continued therapy is futile for the remainder of patients admitted with Trauma Scores of 4 or less if they do not achieve cardiovascular stability in response to appropriate resuscitative measures within 1 hour of admission.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4020909 TI - Macrophage interaction with skeletal muscle: a potential role of macrophages in determining the energy state of healing wounds. AB - A decrease in ATP and creatine phosphate (CP) is characteristic of local injury to skeletal muscle. Recent data have suggested adequate potential for high-energy phosphate production in the wounded tissue. Thus, an adequate explanation for the deficit in the high-energy tissue content in wounds was lacking. Since the wound has multiple components (muscle + cellular infiltrate), the tissue content represents the summation of these components. Therefore, a technique to separate these components was designed. Using a 0.5% solution of lambda-carrageenan as the wounding agent, the extensor digitorum longus muscles (EDL) of male Fisher rats were unilaterally wounded with intramuscular injections. Five days later, both wounded and contralateral nonwounded muscles were incubated in a standardized fashion. The groups of EDL were: wounded as described, contralateral nonwounded, or contralateral nonwounded with the addition to the incubate of 6 X 10(6)/ml lambda-carrageenan elicited peritoneal macrophages. Following incubation, the individual component parts of the system (muscle and macrophage) were rapidly frozen and assayed for high-energy phosphate and DNA content. Examination of the high-energy phosphate content of the separate components of a wound demonstrated that macrophages increased the ATP and CP content of normal skeletal muscle. Yet when total high-energy phosphate content was normalized for total DNA (muscle + macrophages) in the reconstituted system, the values approximated those of wounded muscle.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4020910 TI - Cardiac evaluation following heart injury. AB - Both penetrating and blunt cardiac injuries require urgent management. Delayed sequelae and complications have been reported to occur in 4 to 56% of survivors and frequently required secondary surgical corrections. Between January 1980 and June 1984, 204 patients presented with heart injuries. One hundred twenty-eight of these patients survived. Of the 90 undergoing cardiorrhaphy in the operating room, 78 survived. Two-dimensional (2-D) and pulsed-Doppler echocardiography (echo) and/or cardiac catheterization were performed in 40 patients for suspected significant residual injury. Eight of the 40 required secondary cardiac operations. Two-dimensional echo demonstrated pericardial effusion, abnormal chamber enlargement, abnormal cardiac wall motion, intracardiac missile, and intracardiac and pleural thrombus. Pulsed-Doppler findings included ventricular septal defect, tricuspid insufficiency and right ventricular turbulence secondary to arteriovenous fistulae. Cardiac catheterization detected lesions undetected by 2-D echo in one patient with a gunshot wound. It is concluded that in the absence of cardiac bullets seen on routine chest X-ray, 2-D with pulsed-Doppler echo is an excellent screening technique. With a positive echo study or a residual bullet overlying the cardiac silhouette, cardiac catheterization is indicated in selected patients. PMID- 4020911 TI - Determinants of outcome in pancreatic trauma. AB - Pancreatic injury remains a major source of morbidity and mortality. A previous review of this injury from our department confirmed that the failure to recognize major ductal injuries was a key element in poor outcome of these patients. We evaluated a treatment protocol in 72 consecutive patients that categorized injuries into one of four grades: grade I, pancreatic contusion or minor hematoma with an intact capsule and no parenchymal injury; grade II, parenchymal injury without major ductal injury; grade III, parenchymal disruption with presumed ductal injury; and grade IV, severe crush injury. All grade I and most grade II injuries were treated by drainage alone; the grade III and IV injuries were treated by pancreatic resection. Fifty-seven patients survived longer than 24 hours. There were 23 grade I patients. There were only minimal pancreatic complications and no deaths in this group. Of 18 patients with parenchymal injuries (grade II), only one death occurred, which was due to an inaccurate estimation of the degree of injury and delay in proper treatment. Sixteen patients with grade III and IV injuries were treated by resection with only one death, although the complications rose with increasing severity of the pancreatic injury. The mortality rate from pancreatic causes was 3% (2/57), a reduction from that in a previous report from our institution (19%). Our present study confirms the use of a vigorous diagnostic approach to pancreatic injuries, stresses the value of recognition of major ductal injury, and supports the utility of a treatment protocol in which clinical decisions are based on the severity of the pancreatic injury encountered. PMID- 4020912 TI - Prognosis and survival as determined by visceral amino acid clearance in severe trauma. AB - Sepsis, the commonest cause of late death following severe trauma, is related in part to inadequate uptake of amino acids (AA) and synthesis by the liver and other central tissues of proteins essential to immunological defense. Since 'central plasma clearance rate' of amino acids (CPCR-AA) has been found to reflect these functions, serial measurements of CPCR-AA were made in 32 seriously injured patients of whom ten died (31%), nine of sepsis. The mean Index Severity Score on admission for survivors was 31 +/- 1.8 and in deaths 34 +/- 3.9 (N.S.). The blood plasma AA concentrations were not significantly different. However, early in the course before the onset of infection, CPCR-AA in surviving patients was 227 +/- 30 and in those who ultimately died 83 +/- 24 ml/M2/min (p less than 0.001). Later during sepsis the values of CPCR-AA were 176 +/- 28 and 85 +/- 14 ml/M2/min, respectively (p less than 0.01). Thus CPCR-AA appears to be of value as an indicator of amino acid utilization by central tissues and as a predictor of survival or death following severe trauma. PMID- 4020914 TI - Advances in the management of acute popliteal vascular blunt injuries. AB - This report evaluates critical points in the management of 30 consecutive blunt traumatic popliteal vascular injuries. All arterial injuries were diagnosed both clinically and by Doppler and PVR examinations. Twenty-eight of the 30 arterial reconstructions required interposition bypass grafts, nine of which were PTFE and the remainder were autogenous saphenous veins. In 19 patients the distal anastomosis was made to the distal popliteal artery and in nine patients to the tibial-peroneal arteries. In ten patients in whom limb survival was threatened, the ischemic time was shortened by the use of temporary Silastic shunt for rapid restoration of arterial flow. Nine patients had associated venous injuries which were repaired. Nine of the first 14 patients required fasciotomy but the last 16 patients were treated with hypertonic mannitol and only two of them required fasciotomy. There were no amputations, but in four limbs there were functional losses. In spite of the more extensive damage of blunt trauma, prompt and aggressive management aided by vascular laboratory tests, indwelling shunt, and hypertonic mannitol is rewarded with preservation of limbs following acute popliteal vascular injuries. PMID- 4020913 TI - Management of blunt and penetrating external esophageal trauma. AB - The records of 26 patients with external blunt or penetrating esophageal trauma were reviewed to determine clinical features and results of therapy. Twenty-one injuries (four blunt, 17 penetrating) were to the cervical esophagus, and five to the thoracic esophagus. Major physical signs included subcutaneous air, neck hematoma, and blood in the nasogastric tube. Helpful roentgenographic findings were cervical and/or mediastinal air, mediastinal widening, pleural effusion, and pneumothorax (15%). Nine of 12 (75%) contrast studies and five of six (83%) esophagoscopies were positive. Twenty-four patients had associated injuries, the most common of which was tracheal (14 patients) (64%). All patients were managed by prompt surgical exploration, primary closure, and drainage. There were three early deaths. Thirteen patients had postoperative complications, four of which were esophageal leaks. Two of the leaks caused mediastinitis, pleural sepsis, and led to death. They were not treated by early esophageal exclusion or excision. There were no significant strictures or esophageal sequelae in the other patients. It is concluded that early primary closure and drainage results in a relatively high incidence of survival. If a thoracic esophageal leak occurs, aggressive management of prompt esophageal exclusion or excision is necessary to control sepsis and improve survival. PMID- 4020915 TI - Microbiologic progression of post-traumatic peritonitis. AB - The natural course of post-traumatic peritonitis was studied in 17 pigs. Following a standardized missile wound to the abdomen the pigs were operated on and observed in continuous anesthesia for periods up to 3 days. Bacterial density was measured in peritoneal exudate, parietal peritoneum, laparotomy wound, and projectile entrance and exit wounds at this operation and also at relaparotomy, which terminated the experiments. The bacterial density showed significant perioperative fall, averaging X 1,905 in peritoneal exudate and X 40 in parietal peritoneum. From a low postoperative level (mean c. 10(2)/ml or /gm), bacterial density increased significantly in the observation period. In peritoneal exudate the increase was X 4,073 and in peritoneum X 2,630. In laparotomy and projectile entrance and exit wounds the corresponding figures were X 234, X 126, and X 15. The bacterial population's perioperative reduction and subsequent proliferation were interpreted as reflecting the host defense, which accordingly was limited in capacity and duration. PMID- 4020916 TI - Fractures of the proximal humerus in adults. AB - Fractures of the proximal humerus are a common upper-extremity injury, particularly in the elderly. The literature suggests that the results of treatment of displaced fractures are generally unsatisfactory. Since Neer's articles in 1970 we found little reported in the literature on these fractures. We conclude from our review of 90 fractures that the results of treatment of displaced fractures continue to be unsatisfactory, and we believe that displaced proximal humeral fractures, along with femoral neck fractures, should be classified as unsolved fractures. PMID- 4020917 TI - Successful management of an elderly patient with multiple trauma. AB - An elderly female patient with multiple trauma and flail chest received thoracic and lumbar epidural analgesia and anesthesia, respectively, in the surgical ICU and the operating room. This technique provided segmental analgesia with minimal amounts of narcotics. This allowed for the very important early ambulation and absence of respiratory complications, the main cause of increased morbidity in this age group. PMID- 4020918 TI - Stubbed finger osteomyelitis. AB - Forceful hyperextension of the distal phalanx may result in a Salter II fracture. Due to the anatomic relationship of bone and nail, a 'stubbed finger' injury may result in an inapparent compound fracture. When nail bedding is associated with a distal phalangeal fracture, antibiotics should be instituted. PMID- 4020919 TI - Rupture of the pectoralis major tendon. AB - A case of a rare tendon rupture, well documented with clinical photographs, radiographs, and long-term followup, is reported. It is emphasized that the shoulder region must be carefully examined when a patient presents with a history compatible with pectoralis major tendon rupture. In a physically active individual, primary repair is very important to re-establish normal function and cosmetic appearance following this injury. PMID- 4020920 TI - Ultrastructure of the stomach of the small short-tailed shrew, Blarina brevicauda c. AB - The normal gastric ultrastructure has been characterized for the small short tailed shrew, Blarina brevicauda c., which is a primitive eutherian and one of the smallest living mammals with extraordinarily high metabolic rate. In general the cell types present and cytologic character of gastric mucosal, submucosal, and muscularis cells were similar to that reported for other more advanced small mammalian species. Chief cells, endocrine cells, and lamina proprial elements were morphologically identical to their counterpart in rats, ferrets and other small carnivores. Distinctive cytologic features in this species of shrew included the scanty monolayer or small number of mucous granules in the simple columnar surface epithelial cells of the mucosa, and the thin elongated shape of their microvilli. Dense bodies were absent in the parietal cell mitochondria of the shrew, though usually abundant in other mammalian parietal cells. Our data indicate few morphologic specializations in the shrew stomach which can be correlated with their high rate of food assimilation and metabolic demands, though future studies of mucosal biochemistry and lower gut morphology may reveal such adaptations. PMID- 4020921 TI - Isoproterenol induced fatty change in rat myocardium: freeze fracture study of the sarcolemma at sites of lipid droplet-membrane appositions. AB - Twenty four hours following subcutaneous administration of cardiotoxic doses (85 mg/kg body weight) of isoproterenol (ISO) to male Wistar rats, we observed accumulation of fat droplets in surviving cardiac muscle cells. This finding is consistent with the well established effect of ISO, a beta-receptor stimulant synthetic catecholamine, on lipid metabolism. On thin section electron microscopy lipid droplets were numerous in all surviving cardiac muscle cells, many of them located in close apposition to the sarcolemmal membrane. Freeze fracture electron microscopy revealed at sites of lipid droplet-membrane appositions bulging areas of the sarcolemmal membrane. The plane of fracturing interrupted frequently these bulging areas leaving irregular holes in membrane faces and visualizing the underlying lipid droplets. Intramembrane particles were always uniformly distributed in bulging membrane faces and around interrupted areas suggesting that holes on the sarcolemmal membrane resulted from physical properties of the membrane cleavage and were not related to lipid droplet-membrane fusion. PMID- 4020922 TI - Glomerular endothelial injury related to simple hypothermic storage: an electron microscopic study in the rat. AB - The present study examined alterations in the glomerular endothelium associated with simple hypothermic storage. Adult rat kidneys were flushed with cold Collins (C2) solution and stored at 8 degrees C for 0, 24, 48, 72 and 96 h after which the kidneys were perfusion-fixed and processed for light and electron (scanning and transmission) microscopy. Glomerular endothelium exhibits a time-related increase in endothelial process swelling and fenestral distortion. From 48 to 96 h of preservation, progressive cellular swelling was accompanied by focal elongation and disruption of the fenestral patterns. These changes contrast the maintenance of a normal glomerular epithelial pattern. All of the tubular elements, however, exhibited progressive changes through this time course including cellular necrosis. The glomerular changes associated with simple hypothermic storage are mild, being limited to the endothelium. These changes are probably of little functional significance when compared to the more marked tubular changes. PMID- 4020923 TI - Ciliated neurons in the paraventricular nuclei in old hamsters. AB - The ciliated neurons of the paraventricular nuclei in old hamsters have been studied by electron microscope. These neurons exhibit cilia of 9 + 0 pattern. The single cilia, emerging from typical basal bodies, project into the intercellular space in parallel to the plasmalemma. The basal bodies are connected to ciliary rootlets and close to the Golgi complex. Double or single centrioles in different locations, frequently related to rootlets, can be observed. From a morphological point of view we suggest that these cilia, in the aging process, may represent a sensory structure which could perceive stimuli from the intercellular space. PMID- 4020924 TI - Ultrastructure of the renal granulopoietic tissue of the Rana ridibunda tadpole. AB - The ultrastructure of the renal hemopoietic tissue of Rana ridibunda tadpole has been studied. The main cell types of granulopoietic series are described. No erythropoiesis was found. The heterophilic series contained a first granular type, similar to those described in teleosts and other lower vertebrates but without crystalloid and a second with similar features to 'azurophilic' granules, described in other vertebrates. Specific granules found in mammalians were not observed. The origin and development of the granules have been discussed. Similarly, the eosinophilic series contained two granule types. Mature eosinophilic leukocytes were, at all times, seen in the sinusoidal lumen, a crystalloid core could be either present or absent in the granules. Basophilic leukocytes were extremely scarce, the granule content being homogeneous or crystalline. PMID- 4020925 TI - Fine structure and cytochemistry of the endoplasmic reticulum and its association with the plasma membrane of Leishmania mexicana amazonensis. AB - Promastigotes of Leishmania mexicana amazonensis possess an elaborated system of cytoplasmic membranes which is clearly visualized when the cells are fixed in a glutaraldehyde solution containing Ca++ and post-fixed in an osmium tetroxide solution containing Ca++ and potassium ferricyanide. When the parasites are incubated in a medium containing glucose-6-phosphate and lead nitrate, reaction product indicative of glucose-6-phosphatase activity is seen in the membrane system confirming that it corresponds to the endoplasmic reticulum (ER). A large concentration of profiles of the ER was observed at the anterior region of the cell, close to the flagellar pocket, appearing as a 'proliferative focus'. Profiles of the ER radiate toward the periphery of the cell penetrating between the subpellicular microtubules and reaching the plasma membrane. PMID- 4020926 TI - An improved method for electron microscopic study (SEM and TEM) of vessel prosthesis anastomoses in microsurgery. AB - In order to study the replacement of vessels by biological vascular prostheses in microsurgery, an improved method for scanning electron microscopy preparation which is rapid and minimizes artifacts was developed. To limit endothelial surface injury, the vessel and prosthesis unity is, at first, prefixed by injection into one end of a 2.5% isotonic solution of glutaraldehyde. After fixation by osmium tetroxide, the samples are dehydrated by a graded series of acetone solutions and critical point dried. They are then trimmed around each suture line to pieces of 1 cm including 1/3 vessel and 2/3 prosthesis for further orientation and sectioned longitudinally, with a new razor blade, for microvascular anastomoses observations. The same chemical treatment applied to samples for transmission electron microscopy studies permitted verification of the good preservation of the cellular structures. PMID- 4020927 TI - The morphology of seminiferous tubules of human testicular biopsies. Analysis of the data obtained with two different techniques. AB - Testicular biopsies of fertile men and of azoospermic patients for vas deferens agenesis were processed with two different techniques, i.e. routine histological procedure and semithin sections of electron microscopy preparations. Tubular morphology, testicular biopsy score count and tubular diameter were analyzed in comparison. The two techniques give rise to a different qualitative and quantitative evaluation of all tubular parameters considered. Otherwise they confirm the real existence of the so-called 'tubular blockage' situation with central tubular cellular mass and cell degeneration. PMID- 4020928 TI - Transformation of erythrocytes to spherocytes following incubation with malignant cells. AB - Incubation of erythrocytes from controls and patients with colorectal carcinoma with tumor cells, or their metabolites, caused transformation of the normally shaped cells to spherocytes. It is assumed that abnormal metabolites produced by malignant cells affect the cell membrane inducing the subsequent appearance of spherocytes. The increased destruction of these cells by the reticuloendothelial system may serve as an additional factor for the explanation of anemia accompanying malignant diseases. PMID- 4020929 TI - Frequency distribution and 95% range of a variety of commonly measured blood constituents in healthy Nepalese donors. AB - The most frequently measured biochemical and haematological blood constituents were assayed in 431 healthy Nepalese blood donors. As only 19 subjects were female analysis of their data was confined to calculation of the geometric mean. For the 412 males frequency distribution, geometric mean and 95% range were calculated for each constituent. Male and female male values were compared. It is hoped that 95% normal ranges might provide a better standard against which to compare data from Nepalese patients than the previously used reference ranges derived from ethnically different populations. PMID- 4020930 TI - Cysticercosis in South India. AB - A total of 38 cases of human cysticercosis were diagnosed by histopathological examination within a period of 10 years in JIPMER Hospital which serves the population of Pondicherry and adjoining regions of South India. Analysis of our cases showed that there was no sex predilection and 34 of the 38 cases were within the first three decades of life. A curious yet striking feature was that in 37 of the 38 cases the lesions were localized above the level of the umbilicus. Lesions of the subcutaneous tissue formed the largest group with 18 cases. Seventeen of the 38 cases were confined to the eyes, forming the largest series to be reported from India. In six cases there was evidence of brain involvement with postmortem confirmation in three. The JIPMER Hospital records showed a high incidence of epilepsy in this region with a ratio of one out of every four patients attending the neurology clinic. As cerebral cysticercosis is a known cause of epileptiform convulsions, it is suggested that many cases of epilepsy may in fact be due to cerebral cysticercosis. The majority of our patients were drawn from the rural population. We analysed the social customs and related factors which are peculiar to this region and were indirectly responsible for the high incidence of cysticercosis. PMID- 4020931 TI - Factors associated with birthweight in Bahrain. AB - The birthweights of 6793 infants, based on birth notification forms, were analysed to determine the influence of sex, geographical location, mother's nationality, mother's age, interval between births and number of past deliveries on the birthweight distribution. It was found that these factors contributed significantly to birthweight of the newborn, except for the mother's nationality and the number of past deliveries which were not significant contributory factors. PMID- 4020932 TI - Comparison of normal values of sodium and potassium in plasma of adult Nigerians with those of adult Europeans. AB - Although it has been suggested that there may be adrenocortical hypofunction in Africans as compared to Europeans, very few studies have been carried out to measure whether there is an associated difference in plasma and cellular cation composition. To test this, blood was collected from Nigerians and from European expatriates living in Port Harcourt, and serum sodium and potassium were measured. No differences in serum cation composition were found between the two races. PMID- 4020934 TI - Mothers' knowledge related to child health and nutrition in Ghana and Lesotho. PMID- 4020933 TI - A point survey of periurban and urban malaria in Karachi. AB - A point survey of malaria in Karachi revealed a concentration of malaria cases in the periurban perimeter and marginal areas where immigrating groups, including Afghan refugees and Biharis from Bangladesh are concentrated. Populations of Anopheles stephensi, Karachi's main vector, were low, and were feeding chiefly on buffaloes which are also concentrated along the periurban perimeter. Maintenance of malaria transmission in periurban zones may depend on immigration of susceptibles, bovid hosts which help maintain zoophilic vector populations, and mosquito breeding sites in water tanks or buffalo hoofprints. The vector's switch to man-biting behaviour may occur either due to a 'spillover' effect from buffalo corrals to surrounding houses, or when buffaloes become less available for biting. Four types of chromosome inversions were found in the Karachi An. stephensi; as this species is not a vector in similar habitats in Lahore and Pondicherry where such inversions are not prevalent, it is likely that its status as a vector is related to chromosomal polymorphism influencing behaviour. PMID- 4020935 TI - Birthweights of babies in Benin, Bendel State of Nigeria. PMID- 4020936 TI - Morbidity and mortality in the Mozambican famine of 1983: prevalence of malnutrition and causes and rates of death and illness among dislocated persons in Gaza and Inhambane Provinces. PMID- 4020937 TI - Subjective assessment of lactational performance in Gambian mothers. PMID- 4020938 TI - The weight-for-height chart: is it accurate enough for field surveys? PMID- 4020939 TI - Sudden death in measles and its relationship to serum enzyme and electrocardiographic changes. PMID- 4020941 TI - Infant mortality and socio-economic development in Mauritius. PMID- 4020940 TI - Foreign body airway obstruction in Nigerian children. PMID- 4020942 TI - Therapeutic efficacy of phenobarbital and primidone in canine epilepsy: a comparison. AB - The efficacy of phenobarbital and primidone against canine epilepsy was compared in a controlled study. Thirty-five dogs showing generalized tonic-clonic seizures (grand mal), treated for a minimum of 6 months, were included in the study; fifteen of these were treated with phenobarbital, the other twenty with primidone. Both drugs were dosed according to the clinical requirement; the daily doses ranged from 5-17 mg/kg phenobarbital and from 17-70 mg/kg primidone. The plasma concentrations of phenobarbital, or of primidone and its metabolites phenobarbital and phenylethylmalondiamide (PEMA), were routinely monitored. Complete control of tonic-clonic seizures for 6 months, at least, was attained in six out of fifteen dogs of the phenobarbital group, and in five out of twenty dogs in the primidone group. A further six dogs on phenobarbital, and seven dogs on primidone, were classified as 'improved', i.e. the rate of seizures was reduced by at least 50%. The rest of the dogs were not improved by the treatment. The difference between the efficacy of phenobarbital and primidone was not significant, but primidone gave rise to signs of liver toxicity in fourteen out of twenty dogs, as indicated by considerable elevations of liver enzyme values (alanine transferase, glutamate dehydrogenase, alkaline phosphatase). Phenobarbital is, therefore, regarded as the drug of first choice for the treatment of canine epilepsy. PMID- 4020943 TI - Pharmacokinetics of cefaronide, ceftriaxone and cefoperazone in sheep. AB - The pharmacokinetics of cefaronide (16 gm/kg dose), ceftriaxone and cefoperazone (47 gm/kg dose), after intravenous (i.v.) administration were determined in six Merino ewes. The mean values for terminal half life, steady state volume of distribution Vd(ss), renal clearance (ClR) and total body clearance (ClB) for cefaronide were 1.5 h, 0.39 l/kg, 0.06 l/h/kg and 0.16 l/h/kg, for ceftriaxone; 1.7 h, 0.30 l/kg, 0.08 l/h/kg, and 0.22 l/h/kg, and 0.7 h, 0.16 l/kg, 0.02 l/h/kg and 0.16 l/h/kg for cefoperazone, respectively. After 5.5 h, approximately 42% cefaronide, and after 8 h, approximately 37% ceftriaxone and 13% cefoperazone, was excreted in urine. The non-renal elimination of ceftriaxone and cefoperazone appeared to be more rapid in sheep than is reported in man. Cefaronide was excreted largely unchanged in the urine of sheep. Therefore, the elimination of cefaronide in sheep was similar to that found in man. Cefaronide was well distributed in sheep, whereas ceftriaxone and cefoperazone appeared to be distributed to a lesser degree. These findings underline the different disposition of drugs in different species. PMID- 4020944 TI - Pharmacokinetics of probenecid in sheep. AB - Six Merino ewes were given 1 g (27 g/kg) probenecid by the intravenous (i.v.), intramuscular (i.m.) and subcutaneous (s.c.) routes. After i.v. injection, the biological half-life was 1.55 h and apparent volume of distribution at the steady state (Vdss) 0.18 l/kg. Body clearance (ClB) and renal clearance (ClR) were 0.12 l/h/kg and 0.03 l/h/kg, respectively. Approximately 28% of unchanged probenecid was excreted in urine. Plasma probenecid concentrations after i.v., i.m. and s.c. injections were 133, 37, and 31 micrograms/ml, respectively, at 15 min; 76, 36, and 34 micrograms/ml at 1 h; and 43, 23 and 34 micrograms/ml at 2 h. The average bioavailability of probenecid given by i.m. and s.c. injection was 46% and 34%, respectively. However, after 2 h, probenecid plasma concentrations remained higher when it was given subcutaneously than when it was given intramuscularly. Urine output was correlated positively (P less than 0.05) with kel and ClB. Urine pH increased significantly (P less than 0.01) for the first 2 h, and then steadily declined over the subsequent 6 h. The results suggested that probenecid in sheep was rapidly eliminated because it was rapidly excreted in the normal but alkaline urine. Subcutaneous administration of probenecid in animals may be a useful alternative to oral or i.v. administration. PMID- 4020945 TI - Phenylbutazone and its metabolites in plasma and urine of thoroughbred horses: population distributions and effects of urinary pH. AB - A survey of plasma and urinary concentrations of phenylbutazone and its metabolites in thoroughbred horses racing in Kentucky was carried out. Post-race blood samples from more than 200 horses running at Latonia Racetrack and Keeneland in the Spring of 1983 were analysed. The modal plasma concentration of phenylbutazone was between 1 and 2 micrograms/ml, the mean concentration was 3.5 micrograms/ml and the range was up to 15 micrograms/ml. Oxyphenbutazone had a modal plasma concentration between 1 and 2 micrograms/ml, a mean concentration of 2.07 micrograms/ml and a range of up to 13 micrograms/ml. gamma OH-phenylbutazone had a modal plasma concentration of less than 1 microgram/ml, a mean level of 1.39 micrograms/ml and a range of up to 7.32 micrograms/ml. All plasma concentration frequency distributions were well fitted by log normal distributions. Urinary concentrations of phenylbutazone yielded modal concentrations of less than 1 microgram/ml, a mean urinary concentration of 2.9 micrograms/ml, with a range of up to 30.5 micrograms/ml. This population fitted a log-normal distribution. For oxyphenbutazone the modal concentration was less than 3 micrograms/ml, the mean concentration was 15.26 micrograms/ml, with a range to 81.5 micrograms/ml. The frequency distribution of these samples was apparently bimodal. For gamma OH-phenylbutazone, the modal concentration was less than 4 micrograms/ml, the mean concentration 21.23 micrograms/ml, with a range of up to 122 micrograms/ml. The population frequency distribution for gamma OH phenylbutazone was indeterminate. Analysis of the pH of these post-race urine samples showed a bimodal frequency distribution. The pH values observed ranged from 4.9 to 8.7, with peaks at about pH 5.25 and 7.25. This bimodal pattern of urinary pH values is consistent with observations made in England and Japan. Urinary pH influenced the concentrations of phenylbutazone, oxyphenbutazone and gamma OH-phenylbutazone found in the urine samples. The concentration of these metabolites found in alkaline urines were from 32 to 225 times greater than those found in acidic urines. Plasma concentrations of phenylbutazone and its metabolites, however, were unaffected by urinary pH. In interlaboratory experiments, horses running at Hollywood Park were dosed with phenylbutazone at about 2 g/1000 lbs 24 and 48 h before racing, and a mean dose of 0.6 g/1000 lbs at 72 h prior to racing. Post-race plasma samples from these horses showed phenylbutazone concentrations ranging from 0.44 to 9.97 micrograms/ml, with a mean concentration of 4.09 micrograms/ml.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 4020946 TI - Effect of lidamidine-HCl on Escherichia coli heat-stable enterotoxin-induced jejunal water and electrolyte secretion in neonatal piglets. AB - Neonatal piglets were anesthetized, and two jejunal loops, 20 cm in length, were prepared. Then, either water or 0.12, 0.25, 0.5 or 1.0 mg/kg of lidamidine-HCl was injected intraduodenally on a randomized basis, one treatment per pig. Following this, a crude heat-stable enterotoxin (ST) preparation produced from E. coli no. 1261 was injected into the proximal jejunal loop, and trypticase soy broth (TSB) (with osmolality adjusted to equal the enterotoxin preparation) was injected into the distal jejunal loop. Piglets remained anesthetized for 3 h and were then killed. Fluid was collected from the loops for measurement of volume and Na, K and Cl concentration. Empty loop lengths were measured. There was a significant dose-related reduction of volume and Cl content, and a dose-related, but not significant, reduction in Na content in St-treated loops. A comparison of the mean differences in responses between toxin- and TSB-treated loops indicated that the major 'counter-toxic' effect of the lidamidine was a dose-related increase in water and electrolyte absorption. PMID- 4020947 TI - The effect of copper on intact cattle erythrocytes. AB - The effect of copper on intact cattle erythrocytes was investigated in vitro. When treated with copper, a decrease in the GSH content, accumulation of copper in the cell, loss of potassium and gain of sodium, cross-linking of membrane proteins, and echinocytic transformation were observed. All of these phenomena seem to be caused by a potent oxidant action of copper. These cytotoxic effects of copper were markedly inhibited by the addition of bovine serum albumin in the incubation medium. These results may help to understand the mechanism of hemolysis associated with copper poisoning in vivo. PMID- 4020948 TI - The effect of intermittent treatment with sulphadimidine on coccidiosis in preruminant calves. AB - Preruminant calves excreted coccidia oocysts in their faeces after 3 weeks of group housing. Two weeks of oral sulphadimidine (SDM) administration, 50 mg/kg on the first day of treatment followed by daily administration of 37.5 mg/kg, under the same housing conditions kept the faeces free of oocysts. Three weeks later, these calves excreted oocysts again. Repetition of the same treatment for 2 weeks controlled the infection again, but a second treatment for 5 days did not suffice. The repeated long treatment affected immunoglobulin levels adversely. SDM given repeatedly at a lower dose rate (30 mg/kg) for 1-week periods with medication-free intervals of 1 week controlled the infection and no adverse effects were noted. In comparison with controls, weight gains were greater in treated calves. PMID- 4020949 TI - Furazolidone concentrations in plasma, milk and some tissues of Nubian goats. AB - The concentrations of furazolidone (FZ) in plasma and milk were measured in goats treated orally with the drug at a dose of 10 mg kg-1 daily for 5 days. The maximum plasma concentrations obtained were 1.57 +/- 0.52 micrograms ml-1 (n = 5) 8 h after the first dose, and 2.13 +/- 0.11 micrograms ml-1 (n = 4) 6 h after the fifth dose. The maximum milk concentration was 0.88 +/- 0.32 micrograms ml-1 (n = 4) 8 h following the administration of a single dose. Using a colorimetric method, FZ was not detectable in goats' liver or muscle after the recommended therapeutic dose (10 mg kg-1, 5 days). However, using an HPLC method, the drug was detected 24 h after the treatment in the gluteal muscle and liver at concentrations of 0.26 +/- 0.01 microgram g-1 (n = 5) and 0.10 +/- 0.02 microgram g-1 (n = 5), respectively. The drug concentrations decreased significantly (P less than 0.05-0.01) at 3, 5 and 7 days after treatment, and no measurable concentrations were found after 10 days. PMID- 4020950 TI - Pharmacokinetics of amikacin in the horse following intravenous and intramuscular administration. AB - The pharmacokinetics of amikacin sulfate (AK) were studied in the horse after intravenous (i.v.) and intramuscular (i.m.) administration. Serum (Cs), synovial (Csf) and peritoneal (Cpf) fluid concentrations of the drug were measured. Doses of 4.4, 6.6 and 11.0 mg/kg were given. The concentrations at 15 min following i.v. injection were 30.3 +/- 0.3, 61.2 +/- 6.9 and 122.8 +/- 7.4 micrograms/ml, respectively, for the 4.4, 6.6 and 11.0 mg/kg doses. Mean peak Cs values after the intramuscular injections occurred at 1.0 h post-injection and were 13.3 +/- 1.6, 23.0 +/- 0.6 and 29.8 +/- 3.2 micrograms/ml, respectively. The t 1/2 of amikacin was 1.44, 1.57 and 1.14 h for the 4.4, 6.6 and 11.0 mg/kg doses, respectively. In this study, minimum inhibitory concentrations (MIC) of amikacin sulfate were determined for six pathogens. Based on the MIC and the pharmacokinetic parameters, it would appear that the usual therapeutic dose of amikacin would be between 4.4 and 6.6 mg/kg twice daily and, for the more serious life-threatening infections, dosing three times a day. PMID- 4020951 TI - Absorption kinetics and bioavailability of phenobarbital after oral administration to dogs. PMID- 4020952 TI - A clinical evaluation of Samorin in Trypanosoma evansi infections in Camelus dromedarius. PMID- 4020953 TI - Uncoating of vaccinia virus. AB - Input vaccinia virus deoxyribonucleoproteids with buoyant densities (in CsCl) very similar (if not identical) to those of viral cores have been found in large cytoplasmic structures in which viral DNA replication takes place. The deoxyribonucleoproteids consist of at least five major and two minor core proteins and viral DNA which is protected against DNase digestion. It is suggested that viral core-like deoxyribonucleoproteids rather than released DNA are used in vaccinia-infected cells both for delayed-early gene transcription and viral DNA replication. PMID- 4020954 TI - Interactions among the three adenovirus core proteins. AB - Interactions among the three adenovirus core polypeptides V, VII, and mu were examined, using the reversible chemical cross-linker dithiobis(succinimidyl propionate) and two-dimensional polyacrylamide gel electrophoresis. Cross-linked species obtained from gradient-purified adenovirus type 2 cores were well represented among the cross-linked products of pentonless virions and crude core preparations. The more efficiently formed cross-linked core species were also identified with the arginine-specific cross-linker, p-azidophenyl glyoxal. In addition to dimers of polypeptides V and VII, efficient cross-linking of V to VII, V to mu, and VII to V to mu was detected in adenovirus cores. Notably absent were cross-linked species corresponding to higher multimers of polypeptide VII. A major core-capsid interaction appeared to be via the association of polypeptide V with a dimer of polypeptide VI. PMID- 4020956 TI - A defective ecotropic provirus closely linked to the albino locus. AB - A congenic mouse strain (NFS.C) carrying the albino region of chromosome 7 from strain C58/Lw on an ecotropic virus-negative NFS background inherited a noninducible but apparently full-size provirus reactive with an ecotropic virus specific probe. This unexpressed ecotropic provirus maps close to the albino locus but is distinct from the Fgv-1 provirus located in the same region. The presence of this unique provirus in the albino region of chromosome 7 is potentially important, since it may provide a means of obtaining molecular clones of a chromosomal region, deletions of which are involved in profound metabolic, reproductive, and embryological abnormalities. PMID- 4020955 TI - Adenovirus types 2 and 5 functions elicit replication and late expression of adenovirus type 12 DNA in hamster cells. AB - Human adenovirus type 12 (Ad12) cannot replicate in hamster cells. There is a complete block of viral DNA replication and of the expression of late viral genes. Early viral functions are expressed. In contrast, hamster cells are permissive for human adenovirus type 2 (Ad2). Some of the Ad12-specific functions are insufficient to support viral replication in hamster cells, or else cellular functions are missing or inhibitory for Ad12 replication. It was shown that the block in the replication and late expression of the Ad12 genome in hamster cells could, at least in part, be complemented by Ad2 and adenovirus type 5 (Ad5) functions. When hamster cells were coinfected with Ad2 (or Ad5) and Ad12, both Ad2 (Ad5) and Ad12 DNA replicated. Ad2 (Ad5) virions were produced in double infected hamster cells. The assembly of intact Ad12 virions was not detectable by the techniques used here. The analysis was further refined by Ad12 superinfecting Ad2- or Ad5-transformed cells which carried in an integrated form defined fragments of the Ad2 or Ad5 genome. Persistence and continued expression of the left terminus of the Ad2 or Ad5 DNA in these cells has been documented and helped to support replication and late expression of Ad12 DNA. It remains to be determined which of the E1 functions of Ad2 or Ad5 were responsible for the helper effect. Investigations on the biochemical mechanism of this complementation will entail studies on very complex viral and possibly cellular functions involved in the control of viral gene expression. PMID- 4020957 TI - Quantitative aspects of passive immunity to respiratory syncytial virus infection in infant cotton rats. AB - The amount of passively acquired serum respiratory syncytial virus (RSV) neutralizing antibodies required to protect the respiratory tract of cotton rats against infection was studied. Infant cotton rats were inoculated intraperitoneally with various dilutions of a single pool of sera derived from cotton rats convalescent from RSV infection. After 24 h, these animals were inoculated with RSV intranasally. Virus replication in the respiratory tract was suppressed in cotton rats which had a serum neutralizing antibody titer of 1:100 or greater. Resistance was greater in the lungs than in the nose. Complete or almost complete resistance in the lungs was observed in cotton rats with a serum neutralizing antibody titer of 1:380 or greater. The level of serum RSV neutralizing antibodies required to confer significant resistance to infection in the cotton rat was similar to the level of maternally derived serum antibodies possessed by human infants less than 2 months of age, who as a group exhibit relative resistance to RSV disease compared with infants 2 to 6 months of age. PMID- 4020958 TI - Identification and characterization of a porcine parvovirus nonstructural polypeptide. AB - Sera from porcine parvovirus (PPV)-infected swine fetuses immunoprecipitated and 84- to 86-kilodalton polypeptide in addition to the A and B virion structural proteins. This polypeptide, designated NS-1, was present in PPV-infected cell lysates but not in purified virions. Partial proteolysis mapping revealed that NS 1 was not related to the A and B viral structural proteins. All three proteins in infected cells were phosphorylated at serine residues, and NS-1 also contained phosphothreonine. From pulse-labeling experiments with either 32Pi or [35S]methionine, NS-1 was found to first appear 5 to 7 h postinfection, whereas the viral structural polypeptides were first synthesized 9 to 11 h postinfection. Pulse-chase experiments revealed that NS-1 initially appeared as an 84-kilodalton protein and was subsequently structurally modified to forms of slower electrophoretic mobilities. The time of appearance of NS-1 after virus infection coincided with the initiation of viral DNA synthesis, suggesting that this polypeptide (and the modified forms thereof) may be involved in PPV replication. PMID- 4020959 TI - Development of resistance of enterocytes to rotavirus in neonatal, agammaglobulinemic piglets. AB - The first part of this report describes the development of a technique for evaluating the growth of rotavirus under controlled conditions that approximate a natural infection. A standard dose of rotavirus (approximately 10(9) viral particles) was injected into ligated segments in the small intestine of newborn, agammaglobulinemic, colostrum-deprived piglets. After various periods postinoculation, the segments were retrieved and the enterocytes were evaluated for the presence of rotaviral antigens by immunofluorescence and rotaviral particles by transmission electron microscopy. Peak immunofluorescence in enterocytes was detected at 8 h postinoculation in the upper and middle jejunum and ileum. Transmission electron microscopy at this time revealed fully formed virions which were not seen in sections examined before this 8-h period. The second part of our study describes the use of ligated segments in determining the susceptibility to rotavirus of enterocytes in piglets ranging in age from newborn to 2 weeks. By the time piglets were 2 days old, enterocytes in the upper half of the small intestines appeared to be resistant to rotavirus, whereas those in the lower half seemed partially resistant. Between 4 and 8 days of age, enterocytes in the lower half also became resistant. Resistance paralleled the loss in capacity of piglets to transport macromolecules through enterocytes and was not correlated with the loss in capacity to internalize macromolecules. PMID- 4020960 TI - Degradation of cellular mRNAs induced by a virion-associated factor during herpes simplex virus infection of Vero cells. AB - We have used Northern blot hybridization to study the accumulation of specific cellular mRNAs in Vero cells infected with herpes simplex virus (HSV) type 1 or type 2. HSV-1 infection decreased the cytoplasmic levels of beta- and gamma actin, beta-tubulin, and histone H3 and H4 mRNAs, though not all at the same rate. HSV-2 infection resulted in a more rapid decrease in actin and histone mRNA levels compared with HSV-1 infection. The turnover rate of each type of mRNA studied was accelerated in HSV-infected cells compared with the rate in uninfected cells. Cellular mRNA degradation was induced by HSV infection under conditions of (i) inhibition of de novo protein synthesis, (ii) inhibition of de novo RNA synthesis, (iii) infection with HSV-1(17) tsK, which fails to produce early and late viral gene products at the nonpermissive temperature, and (iv) infection with purified virions in the presence of actinomycin D. We have concluded that, in Vero cells, cellular mRNA degradation is induced by a factor associated with the infecting HSV virion and thus does not require de novo RNA or protein synthesis. Despite the overall inhibition of cellular mRNA accumulation, a novel 2.2-kilobase cytoplasmic actin transcript was produced in HSV-infected cells when viral gene expression was allowed. The level of accumulation of cytoplasmic host mRNAs was compared with the rate of cellular protein synthesis under different conditions of infection. This analysis suggests that both HSV-1 and HSV-2 require an additional function(s) to completely inhibit cellular protein synthesis. PMID- 4020961 TI - Golgi-derived membranes that contain an acylated viral polypeptide are used for vaccinia virus envelopment. AB - A 37,000-dalton polypeptide (p37K) present on purified extracellular vaccinia virus but absent from intracellular virus particles of classical morphology (G. Hiller et al., J. Virol. 39:903-913, 1981; L. G. Payne, J. Virol. 27:28-37, 1978) was further characterized. The polypeptide was only expressed in infected cells after onset of viral DNA replication. Phase partition experiments showed that it is relatively hydrophobic. Although p37K apparently is not a glycoprotein, in vivo radioisotope labeling detected tightly associated palmitic acid. Antibodies to p37K were used to monitor its distribution within infected cells at the light and electron microscopic levels. After synthesis p37K first accumulated in the Golgi region due to a tight membrane association. During progressing infection p37K-carrying membranes were used to form double-walled envelopes around brick shaped vaccinia particles. Within these specialized vesicles vaccinia particles were moved through the cytoplasm toward the cell's surface, presumably along cellular routes for certain secretory products. Finally, single enveloped viruses were released into the extracellular space by an exocytotic process. PMID- 4020962 TI - Analyses of the mRNA transcription processes of snowshoe hare bunyavirus S and M RNA species. AB - The time course of synthesis of snowshoe hare bunyavirus small (S)- and medium (M)-sized viral RNA (vRNA), viral cRNA (vcRNA), and mRNA species was analyzed by using single-stranded DNA probes representing the S- and M-coded gene products. In the presence of puromycin, an inhibitor of protein synthesis, the subgenomic S mRNA species were detected, but not full-length S vcRNA or S vRNA species. No M related RNA species were identified in puromycin-treated cells. In the absence of puromycin, full-length M and S vRNA, S vcRNA, and subgenomic S mRNA species were observed, as well as apparently full-length M vcRNA species, presumably including the approximately similar-sized M mRNA species. The 5' ends of the S and M mRNA species have been shown to be heterogeneous and some 12 to 17 bases longer than the ends of their corresponding presumptive replicative vcRNA species, in agreement with an earlier report that they represent nonviral primer sequences (D. H. L. Bishop, M. E. Gay, and Y. Matsuoko, Nucleic Acids Res. 11:6409-6418, 1983). The 3' ends of the M and S mRNA species were found to be shorter by some 60 and 100 nucleotides, respectively, than those of their corresponding full length vcRNA species. Comparison of the 3' noncoding regions of the S and M vcRNA species revealed that there are conserved sequences following the translation termination codons of the two RNA species. One of these conserved sequences is a pyrimidine-rich template sequence that is approximately 20 nucleotides beyond the deduced S mRNA transcription termination site. PMID- 4020963 TI - Genetic mapping of lymphocytic choriomeningitis virus pathogenicity: virulence in guinea pigs is associated with the L RNA segment. AB - The Armstrong CA 1371 (ARM) and WE strains of lymphocytic choriomeningitis virus (LCMV) differ in the ability to produce disease in adult guinea pigs. Infection with the ARM strain is not lethal, even at high virus doses (greater than 10,000 PFU), whereas the WE strain causes 100% mortality even at low doses (less than 10 PFU). To determine the genetic basis of this virulence, intertypic reassortants were made between the ARM and WE strains of LCMV. The two reassortants with the genotypes WE/ARM (L segment of WE and S segment of ARM) and ARM/WE (L segment of ARM and S segment of WE) were tested for their pathogenicity in guinea pigs. The ARM/WE reassortant was avirulent like the ARM/ARM parental strain. Minimal viral replication was observed in organs of guinea pigs inoculated with 10(2) or 10(5) PFU of ARM/ARM or ARM/WE, and all animals survived. In contrast, the WE/ARM reassortant was highly virulent like the WE/WE parental strain and killed all of the infected animals. High levels of viral replication were observed in guinea pigs infected with the latter two strains. In contrast to these in vivo observations, both the parental strains and the ARM/WE or WE/ARM reassortants had similar growth potential in cultured guinea pig fibroblasts. Thus, the L RNA segment of LCMV WE is important for viral replication in vivo and is associated with fatal acute disease after infection of adult guinea pigs. PMID- 4020964 TI - Interaction between various polymerized human albumins and hepatitis B surface antigen. AB - A variety of albumin polymers were prepared and tested for binding with hepatitis B surface antigen (HBsAg): synthetic polymers cross-linked by either glutaraldehyde or carbodiimide; heat-aggregated polymers made by heating albumin solutions at 60 degrees C for 10 h with or without albumin stabilizer; and polymers isolated from fresh or long-stored commercial therapeutic albumin solutions. A sensitive solid-phase, competitive-inhibition radioimmunoassay, which can detect as little as 10 ng of glutaraldehyde-cross-linked human albumin polymer (PHALB-G), was developed and used to measure binding. The binding of PHALB-G with HBsAg was 150- to 1,000-fold greater than that of any other albumin polymer. Glutaraldehyde-cross-linked bovine albumin polymer showed no binding. Albumin monomer and dimer fractions produced by glutaraldehyde treatment exhibited some binding, albeit much weaker than PHALB-G. As measured by a direct binding assay with solid-phase PHALB-G, the attachment of HBsAg particles from sera positive for antibody to the e antigen was less efficient than that from sera positive for e antigen, even when all sera were tested at equal HBsAg concentrations. In protein blot experiments with radiolabeled albumin preparations, PHALB-G bound almost exclusively to HBsAg polypeptide P31 and showed no binding with the major polypeptides P23 and P26. None of the other radiolabeled albumin polymers was reactive. These results indicate that the interaction between PHALB-G and HBsAg is not due to polymerization of albumin per se, but rather is unique and site specific. PMID- 4020965 TI - Identification and predicted sequence of a previously unrecognized small hydrophobic protein, SH, of the paramyxovirus simian virus 5. AB - A previously unrecognized gene (SH) has been identified on the virion RNA of the paramyxovirus simian virus 5 between the genes for the fusion protein and the hemagglutinin-neuraminidase. An SH mRNA of 292 nucleotides (plus polyadenylate residues), transcribed from the SH gene, has been identified. The SH mRNA contains a single open reading frame which encodes a polypeptide of 44 amino acids with a molecular weight of 5,012. The SH polypeptide is predicted to contain an extensive hydrophobic region. This protein has been identified in simian virus 5-infected cells, and it has been shown to be encoded by the SH mRNA by in vitro translation of size-fractionated mRNAs, hybrid-arrest translation, and hybrid-selection translation. PMID- 4020966 TI - ts1, a Paralytogenic mutant of Moloney murine leukemia virus TB, has an enhanced ability to replicate in the central nervous system and primary nerve cell culture. AB - A temperature-sensitive mutant of Moloney murine leukemia virus TB (MoMuLV-TB), ts1, which is defective in intracellular processing of envelope precursor protein (Pr80env), also possesses the ability to induce hind-limb paralysis in infected mice. To investigate whether ts1 has acquired neurotropism and to determine to what extent it can replicate in the central nervous system, we compared viral titers in the spleen, plasma, spinal cord, and brain throughout the course of infection of mice infected with ts1 and parental wild-type (wt) MoMuLV-TB. In both the ts1- and wt-inoculated mice, the concentrations of infectious virus recovered from the plasma and spleen increased rapidly and reached a plateau by 10 days postinfection (p.i.). In contrast, virus concentrations in the spinal cord and brain of ts1-inoculated mice increased gradually and reached a titer comparable to that in the spleen and exceeding that in the plasma only at 25 to 30 days p.i. At this time, the virus titer was approximately 200X greater in ts1 infected spinal cord tissue and approximately 20X greater in ts1-infected brain tissue than in the same wt-infected tissues. Paralysis became evident at 25 to 30 days p.i. in ts1-inoculated mice, whereas the wt-inoculated mice were normal. In addition, a substantial amount of Pr80env was detected in the spinal cords of ts1 inoculated mice compared with that found in the spinal cords of wt-inoculated mice. The infectious virus isolated from ts1-infected nerve tissue was found to possess the characteristic phenotype of the ts1 virus. Microscopic lesions of ts1 inoculated mice at 30 days p.i. consisted of vacuolar degeneration of motor neurons and spongy change of white matter in the brain stem and spinal cord. Similar but less severe lesions were observed in wt-inoculated mice. With primary cultures of central nervous system tissue we showed that ts1 can infect and replicate in both neuron and glial cells. In contrast, although wt MoMuLV-TB replicated in glial cell-rich culture, viral replication was barely detectable in neuron-rich culture. PMID- 4020967 TI - Pathogenesis of street rabies virus infections in resistant and susceptible strains of mice. AB - Seven strains of mice were examined to determine why susceptibility differences and variations in clinical central nervous system (CNS) disease occurred among these animals after intraperitoneal inoculation of street rabies virus (SRV). Trace experiments for infectious virus indicated that these differences were associated with restriction of virus replication within the CNS. Limitation of viral replication appeared to correlate with the antibody response in that prominent serum anti-SRV neutralizing antibody titers were detected in resistant strains, whereas susceptible strains produced minimal amounts of antibody until their death. The importance of the immune response was reaffirmed with cyclophosphamide studies in that all resistant SJL/J mice died after immunosuppressive treatment. In contrast, cyclophosphamide-treated SJL/J mice whose immune systems were reconstituted with either unfractionated immune spleen cells or with sera 24 h after SRV inoculation survived a lethal dose of SRV. More importantly, immunosuppressed SJL/J and immunodeficient athymic mice were protected when reconstituted with immune serum 72 h after SRV inoculation, a time in which infectious virus was detected in the spinal cords of some mice but was not present in the peritoneal cavity. Additional studies showed that antibody in the cerebrospinal fluid was unimportant in the resistance of mouse strains which remained clinically asymptomatic, but it appeared to be associated with the survival of mice which developed clinical CNS disease. Furthermore, CNS resistance to intranasal or intracerebral inoculation with challenge virus standard rabies virus developed as early as 5 days post-intraperitoneal inoculation of SRV. PMID- 4020968 TI - Infectious entry of murine retroviruses into mouse cells: evidence of a postadsorption step inhibited by acidic pH. AB - The entry into cells by many enveloped RNA viruses is accomplished by endocytosis and subsequent penetration of the endosomal membrane by an acidic pH-dependent fusion event. In the current study, we examined early events in the infectious entry of mouse retroviruses, using as a framework the observation that infection of a mouse tail skin cell line by the ecotropic virus Friend murine leukemia virus was inhibited at mildly acidic pH (pH 6). This inhibition operated on a postadsorption step, since binding of virus was unaffected at this pH. The rate of penetration of preadsorbed virus, which displayed first-order kinetics, was markedly affected by changes in the pH of the medium. The half-time for disappearance of infectious cell surface virus at 37 degrees C was approximately 10 min at pH 7.6. At pH 6.0, however, greater than 98% of the adsorbed infectivity remained at the cell surface after 45 min. This cell surface virus, though not infecting the cell at pH 6.0, retained its capacity to enter and infect the cell when the pH of the medium was raised. Acidic pH had little effect on the rate of fluid uptake by the cells, as measured by internalization of [3H]sucrose, indicating that global inhibition of endocytosis had not occurred. In contrast, cell fusion induced by Friend murine leukemia virus was optimal at pH 7.6 but markedly inhibited at a pH of less than 6.4. This inhibitory effect of acidic pH on membrane fusion is unique among the enveloped viruses which have been studied and would preclude entry of Friend murine leukemia virus from within acidified endocytic vesicles. Entry of other members of the ecotropic, mink cell focus-forming, and xenotropic host range groups displayed similar pH sensitivity. However, one xenotropic virus was relatively resistant to the effect of acidic pH, suggesting that differences might exist in the requirements for entry of different retroviruses. PMID- 4020969 TI - Effect of monensin on the assembly of Uukuniemi virus in the Golgi complex. AB - The effect of the carboxylic ionophore monensin on the maturation of Uukuniemi virus, a bunyavirus, and the transport of its two membrane glycoproteins, G1 and G2, were studied in chicken embryo fibroblasts and baby hamster kidney cells. Virus maturation, which occurs in the Golgi complex (E. Kuismanen, K. Hedman, J. Saraste, and R. F. Pettersson, Mol. Cell. Biol. 2:1444-1458, 1982; E. Kuismanen, B. Bang, M. Hurme, and R. F. Pettersson, J. Virol. 51:137-146, 1984), was effectively inhibited by the drug (1 or 10 microM) as studied by electron microscopy and by assaying the release of infectious or radiolabeled virus. Immunoelectron microscopy showed that association of viral nucleocapsids with the cytoplasmic surface of glycoprotein-containing Golgi membranes, a prerequisite for virus budding, was unaffected by monensin. In the presence of the drug, the virus glycoproteins assembled into long, tubular structures extending into the lumen of Golgi-derived vacuoles, suggesting that monensin inhibited a terminal step in the assembly of the virus. Intracellular transport and expression of the virus membrane glycoproteins G1 and G2 at the cell surface were not inhibited by monensin as studied by immunocytochemical and radiolabeling techniques. Pulse chase experiments in the presence of monensin showed that intracellular G1 acquired only partially endo-H-resistant glycans. The sialylation of G1 appearing on the cell surface in the presence of the drug was decreased, whereas sialylation of G2 apparently was inhibited to a lesser extent, as shown by external labeling of the cells with the periodate-boro[3H]hydride method. Thus, monensin exerted a differential effect on the terminal glycosylation of G1 and G2. Unlike several membrane and secretory glycoproteins, both G1 and G2 could enter a functional transport pathway in the presence of monensin and become expressed at the cell surface. PMID- 4020970 TI - Properties of monoclonal antibodies against glycoproteins of western equine encephalitis virus. AB - To analyze the biological activities of the alphavirus glycoproteins, eight different monoclonal antibodies against the two glycoproteins of western equine encephalitis virus were isolated. Five of the eight monoclonal antibodies were shown to be specific for E1 and three for E2 protein by an enzyme-linked immunosorbent assay and by radioimmunoprecipitation. Three of the five anti-E1 and all of the anti-E2 monoclonal antibodies inhibited hemagglutination by purified virions. One anti-E1 and two anti-E2 monoclonal antibodies possessed high virus-neutralizing activity. PMID- 4020971 TI - mRNA activity of a Sindbis virus defective-interfering RNA. AB - We obtained Sindbis defective-interfering particles by nine and undiluted passages of standard virus on chicken embryo fibroblasts. These particles contain a deleted 20S RNA molecule which has mRNA activity, as shown by translation in cell-free systems in vitro. In infected cells, this mRNA activity appeared to be totally inhibited except at very late times postinfection. PMID- 4020973 TI - Recognition, qualification and certification. PMID- 4020972 TI - trans-Activation of parvovirus P38 promoter by the 76K noncapsid protein. AB - The autonomously replicating parvoviruses contain a 5-kilobase linear single stranded DNA genome that produces two noncapsid proteins, N1 and N2, and two overlapping capsid proteins, VP1 and VP2. To characterize the regulation of viral transcription, we began with a study of the promoter for the coat proteins (P38) at map unit 38. Various constructions containing the P38 promoter were fused to the bacterial gene for chloramphenicol acetyltransferase (cat), and the relative efficiency of expression was determined in the presence and absence of parvovirus gene products. Our results show that the P38 promoter is a weak promoter without a trans-activation mediated by the 76,000-molecular-weight (76K) N1 protein. The N1 protein, supplied either by superinfection with virus or cotransfection with the cloned N1 gene, increased greatly the expression of the P38 promoter. In addition, sequences 3' to the promoter, within the region + 127 to + 648 (assuming an mRNA start site at 2008), were required for optimal expression but not for trans-activation. These results suggest that the production of parvovirus capsid proteins is under the indirect control of the P4 promoter and one of its gene products. PMID- 4020974 TI - Nonoperative management of renal stab wounds. AB - A prospective clinical study of 54 patients with stab wounds and hematuria was conducted to evaluate the safety of selective nonoperative management compared to mandatory surgical exploration of these patients. In the absence of signs of severe blood loss, associated intra-abdominal injury or major abnormality on the excretory urogram patients were randomized to undergo mandatory surgery (group 1) or nonoperative management (group 2). Patients with signs of severe blood loss, associated intra-abdominal injury or gross abnormality on excretory urography were selected for an operation (group 3). The rate of probably needless operations (defined as minor renal injury without associated intra-abdominal lacerations) was 78 per cent in group 1 and 0 per cent in group 3. Pulmonary complications occurred in 33 per cent of the patients in group 1, 4 per cent in group 2 and 38 per cent in group 3. Despite an operation delayed renal hemorrhage occurred in 1 patient (5 per cent) in group 1 and 2 (15 per cent) in group 3, and resulted in nephrectomy in 2 of these patients. No instance of secondary hemorrhage occurred in group 2 patients. The mean length of hospitalization was 9, 5 and 11 days in groups 1 to 3, respectively. Our results indicate that the selective nonoperative management of patients with renal stab wounds can lead to a decrease in the rate of unnecessary operations, postoperative complications and length of hospitalization compared to a policy of mandatory surgical intervention. PMID- 4020975 TI - Cystadenocarcinoma of the kidney: a profile of 13 cases. AB - Cystadenocarcinoma is an uncommon variant of renal cell carcinoma that is cystic in appearance. Our experience with 13 of these tumors is presented. The biological behavior was similar to renal cell carcinoma in general, although a greater proportion presented as stage I lesions. Computerized tomography and cyst aspiration may be helpful to differentiate these tumors from simple cysts. PMID- 4020976 TI - Anterior bladder tube: 4 forms for incontinence of different etiology. AB - We treated 20 male and 7 female patients with total urinary incontinence of variable etiology by construction of 4 different forms of the anterior bladder flap tube. The Tanagho procedure was used in 10 patients and 3 variants of the operation were fashioned to correct the particular defects present in the remaining 17. The high success rate of 85 per cent is due largely to the selection of the proper form of the tube for each case of urinary incontinence. PMID- 4020977 TI - Fractures of the penis seen in Abu Dhabi. AB - We report on 9 patients with fracture of the penis seen during 5 years in a single hospital serving only part of a city population of less than 300,000 persons. Of the 9 patients 7 were expatriates unaccompanied by their wives. This factor possibly is significant in the social etiology of this injury. Two patients presented late and were managed conservatively, with a poor result in 1 who was not lost to followup. Of the 7 patients who underwent immediate penile exploration, evacuation of hematoma and repair of the defect 6 had no resultant penile deformity and 1 had mild shaft curvature on erection, while all retained erectile potency. We advocate an operation as the method of treatment. PMID- 4020978 TI - Dynamic cavernosography: venous outflow studies of cavernous bodies. AB - Based on dynamic cavernosography studies in 15 patients, including 8 with simultaneous passive erection, we present more precise details of the venous drainage of the penis. The venous drainage is comprised of 3 different systems. The superficial dorsal vein drains mainly the penile skin and prepuce, and empties via the external pudendal veins into the femoral vein. The deep dorsal vein, located between the tunica albuginea and Buck's fascia, drains the glans and all 3 corpora. The venae profundae penis emerge from each crus of the corpora cavernosa and drain only the corpora themselves. Considerable individual differences were found regarding further drainage via the pelvic venous system, including the prostatovesical plexus and internal pudendal veins. Passive erection was tried in 11 patients and was successful immediately after cavernosography in 8. The flow rates to induce an erection averaged 111 ml. per minute (range 55 to 160 ml. per minute), while the rate to maintain the erection was 48 ml. per minute (range 12 to 90 ml. per minute). PMID- 4020979 TI - Early orchiectomy for patients with stage D1 prostatic carcinoma. AB - Staging lymphadenectomy revealed stage D1 disease in 30 of 94 patients with clinically localized prostatic carcinoma. Early orchiectomy resulted in a 46 per cent treatment failure rate after 45 months and established local disease control in almost all patients. The interval to treatment failure in this group compares favorably to the progression rate in patients treated with other modalities. PMID- 4020980 TI - Detrusor areflexia in suprasacral spinal cord injuries. AB - Patients with high thoracic or cervical spinal cord injuries normally have a detrusor contraction during cystometry. Thirteen patients with detrusor areflexia and a high spinal cord lesion underwent neurophysiological evaluation with electromyography of the pelvic floor muscles, lumbosacral-evoked potential to tibial nerve stimulation, the bulbocavernosus reflex and water cystometry. Two groups of patients were identified. Of those patients with initial detrusor areflexia evidence was found for a subclinical second lesion involving the lumbosacral arc, which accounted for the acontractile bladder. In the remaining patients of this group, who had an intact sacral reflux arc, a detrusor contraction developed after a mean of 16.6 months from the date of injury. The second group of patients exhibited initial detrusor hyperreflexia that subsequently converted to areflexia. A reason was found for the alteration in bladder behavior in each case. The possible reasons for differential recovery of the somatic and autonomic nervous systems are discussed together with a rationale for the second subclinical spinal cord lesion. The most predictive neurophysiological test was electromyography of the pelvic floor. PMID- 4020981 TI - The use of topical vasodilators as an adjunct in infant renal surgery. AB - In infant renal surgery there is a well recognized problem with vasospasm and resultant renal ischemia. Recently, we applied vasodilators to the perivascular tissues during renal surgery to prevent vasospasm. With this mode of treatment no renal units were lost owing to ischemia secondary to the operative procedure. The treatment has been especially useful in infants with duplicated systems undergoing partial nephroureterectomy. Owing to the diminutive size of infant renal vessels, vasospasm can be triggered easily even with the most careful hilar dissection. Thus, to assure maximal preservation of tissue, vasospasm must be prevented before renal mobilization and hilar dissection. Therefore, to prevent the development of renal ischemia in infants undergoing renal surgery we recommend initial exposure of the hilar vessels before dissection, application of papaverine and lidocaine to the perivascular tissues, and delaying further dissection until maximal vasodilation has occurred. PMID- 4020982 TI - Cutaneous vesicostomy experience in infants and children. AB - Cutaneous vesicostomy has proved to be a useful form of temporary diversion in children. We report our experience with 35 patients who underwent diversion for either lower tract dysfunction or obstruction. In only 1 child did vesicostomy appear to be of questionable value in adequately draining the upper urinary tracts. Renal functional improvement or stabilization was observed in the remaining 34 children. Complications occurred in 14 patients, with urinary tract infections of a clinically serious nature being observed in 6. Our experience tends to confirm vesicostomy to be an effective, simple and easily reversible means to treat selected conditions in infants and children. Complications are encountered but they have been managed effectively. PMID- 4020983 TI - Transverse ureteral advancement technique of ureteroneocystostomy (Cohen reimplant) and a modification for difficult cases (experience with 121 ureters). AB - We reimplanted 121 ureters by the Cohen technique. A modification is introduced for difficult cases, making the Cohen technique more adaptable for dilated ureters and small bladders. Radiographic studies obtained at least 6 months after reimplantation revealed only 1 case of persistent reflux (grade I), no case of contralateral reflux and no obstruction. Even though the series included 35 ureters with grade V primary reflux and 7 primary obstructive megaureters, only 7 ureters were tapered. This finding suggests that the Cohen method might require tapering in a smaller percentage of cases compared to other reimplantation techniques. PMID- 4020984 TI - Muscarinic cholinergic receptors in bladder exstrophy: insights into surgical management. AB - The surgical management of classical bladder exstrophy (functional bladder closure or urinary diversion) should be influenced by the inherent detrusor function of the exstrophied bladder. Cystometrograms performed previously on individuals with successful exstrophy closures demonstrate normal bladder function. The biochemical and neurophysiological properties of the exstrophied bladder have otherwise not been investigated. In this study radioligand receptor binding techniques were used to compare the density and equilibrium dissociation constant of muscarinic cholinergic receptors in control and exstrophy bladders. The density of muscarinic cholinergic receptors in the control and exstrophy groups was 1.97 plus or minus 0.29 and 1.44 plus or minus 0.21 fmol. per microgram deoxyribonucleic acid (mean plus or minus standard error of mean), respectively. The dissociation constant of the control and exstrophy groups was 0.15 plus or minus 0.02 and 0.14 plus or minus 0.02 nM. (mean plus or minus standard error of mean), respectively. These data show that the muscarinic receptor density and binding affinity in control and exstrophy bladders are similar. Therefore, the neurophysiological composition of the exstrophied bladder is not grossly altered during the anomalous development. PMID- 4020985 TI - Tunica vaginalis free graft for the correction of chordee. AB - Tunica vaginalis free grafts were used to correct severe chordee not amenable to other surgical maneuvers in 11 boys. Postoperatively, the penis was straight in 10 patients and had some degree of downward angulation in 1 boy. The tunica vaginalis free graft seems to be a useful technique for the correction of severe chordee. PMID- 4020986 TI - Percutaneous catheter drainage of post-traumatic urinoma. AB - We report a case that demonstrates that percutaneous catheter drainage may be considered as an alternative to surgical intervention in the treatment of urinomas, especially when there is no persistent ureteral obstruction. PMID- 4020987 TI - Percutaneous endopyelopyelotomy: endourological management of a bifid pelvis with ureteropelvic junction obstruction. AB - A patient with a bifid renal pelvis and a severely stenotic ureteropelvic junction was managed successfully by creating a fistula between the 2 renal pelves with a direct vision urethrotome, and intubating the fistula with a circle tube and a universal stent for 6 weeks. This endourological procedure spared this obese diabetic patient from an open operation. PMID- 4020988 TI - Misleading features of blind-ending bifid ureter on computerized tomography examination. AB - A blind-ending bifid ureter presents a confusing picture on cross-sectional imaging of the descending course of an apparently duplicated ureter. Such factors should raise suspicion of this diagnosis and be confirmed with retrograde pyelography or excretory urography. PMID- 4020989 TI - Ureteral obstruction secondary to a patent umbilical artery in a 79-year-old man: a case report. AB - Aberrant blood vessels are a rare cause of ureteral obstruction, with 9 cases having been reported, mostly in children. A 79-year-old man presented with left flank pain. At operation a patent left umbilical artery was partially obstructing the distal left ureter. Partial ureterectomy and ureteroureterostomy provided relief of symptoms. Aberrant blood vessels should be considered in the differential diagnosis of extrinsic distal ureteral obstruction. PMID- 4020990 TI - Stone formation as a complication of indwelling ureteral stents: a report of 5 cases. AB - The silicone ureteral catheter has proved to be an invaluable addition to the armamentarium of the urological surgeon and, infrequently, it is associated with complications. We report 5 cases of stone formation associated with indwelling silicone ureteral catheters. PMID- 4020992 TI - Prostatic and membranous urethrorectal fistulas: a new technique of surgical closure. AB - We report on a quick, safe and simple procedure, the anterior perineal trans anorectal approach, which was used successfully to treat 2 difficult cases of prostatorectal and membranous urethrorectal fistulas. This method was devised after a review of all techniques to treat these fistulas, which are known to be difficult. Our 2 cases, like others, demonstrate the harmlessness of anterior section of the anal sphincter, provided the sphincter is repaired correctly. This approach should be used in patients with urethroprostatorectal pathological conditions for whom a perineal access is contemplated. PMID- 4020991 TI - Treatment of radiation-induced cystitis with hyperbaric oxygen. AB - The effects of hyperbaric oxygen on radiation cystitis have been documented in 3 patients with radiation-induced hemorrhagic cystitis refractory to conventional therapy. Cessation of gross hematuria and reversal of cystoscopic bladder changes were seen in response to a series of hyperbaric oxygen treatments of 2 atmosphere absolute pressure for 2 hours. To our knowledge this is the first report of cystoscopically documented healing of radiation-induced bladder injury. PMID- 4020993 TI - Megalourethra. AB - We present 5 examples of megalourethra. All 5 cases were associated with the spectrum of the triad syndrome, ranging from minor hydronephrosis and undescended testis to gross hydronephrosis incompatible with survival. Initial management of this urethral defect is drainage followed later by reconstruction. PMID- 4020994 TI - Voiding dysfunction in Shy-Drager syndrome. AB - The neurological syndrome described by Shy and Drager includes urinary symptoms of incontinence and retention. We present the urodynamic evaluation of 2 patients with this syndrome, which demonstrated different sources for the symptoms and led to 2 separate effective treatments. PMID- 4020995 TI - Spontaneous thrombosis of left spermatic vein: report of 2 cases. AB - We report 2 cases of spontaneous thrombosis of the left internal spermatic vein causing acute development of a painful scrotoinguinal mass. Both patients were treated by surgical ligation and excision of the thrombosed vein. Venous congestion and testicular ischemia occurred in 1 patient who required orchiectomy for massive swelling and pain. Based on our recent experience, we recommend conservative management of spontaneous spermatic vein thrombosis with anticoagulation (and possibly antibiotics). PMID- 4020996 TI - Effects of varicocele after unilateral orchiectomy and sympathectomy. AB - An experimental varicocele was created in the adult rat by partial ligation of the left renal vein. There was a significant bilateral elevation of both testicular blood flow and temperature in the varicocele animals (p less than 0.01). Mean testicular blood flow for control and varicocele animals was 29.6 +/- 1.0 and 39.8 +/- 2.0 ml./min./100 gm. tissue, while mean testicular temperature was 34.4 +/- 0.1 and 35.3 +/- 0.2C, respectively. A left orchiectomy was combined with a left varicocele to determine if the left testis is essential for the right testicular response to a varicocele. Elevation of right testicular blood flow was not altered by left orchiectomy (p less than 0.05); however, right testicular temperature was no longer significantly increased. Mean right testicular blood flow and temperature for this group was 39.0 +/- 1.5 ml./min./100 gm. tissue and 34.2 +/- 0.15C, respectively. A left sympathectomy was combined with a left varicocele to ascertain if the right testicular response to the left varicocele was mediated through a neural pathway. A significant bilateral increase in testicular blood flow was noted with a left sympathectomy alone, and thereby masked the ability to evaluate the right testicular response to the simultaneous left sympathectomy and varicocele. Elevation of right testicular blood flow in response to the left varicocele is independent of the presence of a left testis and any immune response it may stimulate. The role of the sympathetic nervous system as a mediator of the bilateral varicocele effect remains undetermined. PMID- 4020997 TI - Experimental obstructive hydronephrosis in newborn rats. VI. Long-term effects on glomerular filtration and distribution. AB - Partial obstruction of one ureter was created in newborn rats and its effects were studied after the rats matured. The obstructed pelvis was found to be considerably enlarged. The parenchymal weight was 19 per cent lower and the whole kidney glomerular filtration rate was 43 per cent lower than on the contralateral intact side (p less than 0.001); however, these figures probably include a compensatory increase on the intact side. In the central part of the cortex, the glomerular filtration rate/mg. cortex was 21 per cent lower in the hydronephrotic kidney (p less than 0.02), but there was no intracortical redistribution. The glomerular density in this region was 24 per cent higher on the hydronephrotic side (p less than 0.001), because the glomeruli were crammed together in the distended cortex. No redistribution of glomeruli was found. The results are discussed and compared with previous findings from our laboratory. In this model, partially obstructive uropathy was found to cause only a moderate depression, but no redistribution, of the filtration. PMID- 4020998 TI - Varicocele: temporal considerations. AB - The pathophysiology of the abnormal spermatogenesis seen in the presence of the varicocele has not been elucidated in spite of extensive study. Furthermore, no satisfactory explanation exists for the bilateral abnormal spermatogenesis seen in a process which is felt to be unilateral in the majority of cases. The present study was designed to determine if a surgically produced unilateral varicocele would lead to ipsilateral testicular changes prior to the onset of contralateral testicular alterations. Utilizing the rat model and microsurgical techniques, the effects of the varicocele on ipsilateral and contralateral spermatogenesis was studied at intervals over 49 days. Mean seminiferous tubular diameter measurements and flow cytometric analysis of testicular tissue were utilized to assess spermatogenesis. A statistically significant decrease in mean seminiferous tubular diameter was seen between day 1 and day 49 in the left testicle. The right testicle tended to demonstrate similar changes but these were not significant by the method of analysis used. Flow cytometric analysis of testis DNA content also revealed a statistically significant difference in the percentage of haploid, diploid and tetraploid cells in the left testis on day 1 as compared to day 49. The right testis again tended to demonstrate similar but not significant changes. Though primarily a unilateral process, bilateral spermatic vein abnormalities were also visualized in some animals. This observation may contribute to the bilateral effect observed. These studies demonstrate that a surgically created left varicocele will result in bilateral testicular alterations. Within the time frame of the study, the ipsilateral alterations progressed to a greater degree. PMID- 4020999 TI - Characterization of the muscarinic cholinoceptors in the human detrusor. AB - Contractions of the human detrusor are thought to be mediated mainly via cholinergic muscarinic receptors. In the present study, we used a receptor binding technique with 1-quinuclidinyl[phenyl 4-3H]benzilate ((-)3H-QNB) as radioligand to directly demonstrate the presence of muscarinic receptors in homogenates of the human detrusor. The binding of (-)3H-QNB was of high affinity (KD = (1.2 +/- 0.1) X 10(-10) M), saturable (Ro = 160 +/- 15 fmol./mg. protein) and possessed the pharmacological specificity expected of an interaction with muscarinic receptors. Muscarinic receptor antagonists were bound to a virtually uniform population of sites, whereas muscarinic receptor agonists recognized more than one population of muscarinic binding sites. The affinities of a series of antimuscarinic drugs, determined in competition experiments with (-)3H-QNB, were found to correlate with the capacity to inhibit carbachol-induced contractions in isolated human bladder muscle. Binding data together with the functional data indicated that the human detrusor does not contain any significant number of muscarinic spare receptors. The results suggest that a selective effect on the muscarinic receptors of human bladder is not possible to obtain with presently available antimuscarinic agents. PMID- 4021000 TI - Newly awakened interest in sleep research spans many specialties. PMID- 4021001 TI - Leads from the MMWR. State legislation concerning use of safety belts--United States, 1985. PMID- 4021002 TI - Leads from the MMWR. Cutaneous leishmaniasis--Ohio. PMID- 4021003 TI - Leads from the MMWR. Measles on college campuses--United States, 1985. PMID- 4021004 TI - Asbestos-related diseases. PMID- 4021005 TI - Colors, races, languages, and diseases. PMID- 4021006 TI - Ascorbic acid and urinary pH. PMID- 4021008 TI - Salivary thiocyanate in smokers. PMID- 4021007 TI - Treatment of genetic hormonal deficiencies by nicotine. PMID- 4021009 TI - Sudden and unexpected natural death in childhood and adolescence. AB - The descriptive epidemiology of sudden nontraumatic death from persons aged 1 to 21 years was studied in a defined population. In nine years, the 207 deaths in this group (4.6/100,000 population/per year) comprised 22% of nontraumatic mortality. Age-specific rates were highest between 1 and 4 years (mainly infections and undetermined causes) and 14 and 21 years (mainly cardiovascular, epilepsy, intracranial hemorrhage, and asthma). Nonwhite rates were higher than whites, and white males had higher rates than white females. Referral for medicolegal evaluation was inconsistent. Only 18% died at university hospitals. Infections included lower respiratory tract and septic shock. The main cardiac diagnosis was myocarditis. Most epilepsy deaths were unwitnessed and had absent or low anticonvulsant levels. Eighty-five cases had a known associated chronic illness and 111 reported prodromal symptoms. Prevention of these events requires improved identification and management of antecedent conditions. PMID- 4021010 TI - Fatalities in the Peace Corps. A retrospective study: 1962 through 1983. AB - Fatalities among Peace Corps volunteers were analyzed for 1962 through 1983, with individual case histories reviewed for all deaths from 1977 through 1983. Unintentional injuries accounted for 70% of the 185 deaths of Peace Corps volunteers, with motor vehicle crashes the number 1 cause of death. The death rate from unintentional injuries for women was significantly higher than the comparable US rate. Motorcycles caused 12% of all Peace Corps deaths and 33% of all motor vehicle deaths. Suicide has emerged as a leading cause of death among volunteers, accounting for 13% of all deaths from 1981 through 1983. Greater emphasis on injury control measures is needed to reduce this toll. PMID- 4021012 TI - Office evaluation of the pacemaker patient. Detection of normal and abnormal pacemaker function. PMID- 4021011 TI - Plasma lipoprotein levels in vegetarians. The effect of ingestion of fats from dairy products. AB - The influence of dairy foods in the diet on plasma levels of total, low-density lipoprotein, and high-density lipoprotein cholesterol (TC, LDL-C, and HDL-C, respectively) was studied in 75 adult lactovegetarians living in the northeastern United States. Dairy products were the major sources of dietary saturated fat and cholesterol. The plasma TC level was positively correlated with dietary saturated fat and dietary cholesterol, and inversely correlated with the ratio of polyunsaturated to saturated fats in the diet. Correlations between the LDL-C level and the nutrients were similar to those of the TC level. The HDL-C level was not significantly related to any nutrients in the diet. The cholesterol levels of the lactovegetarians were compared with those of strict vegetarians. Lactovegetarians had 24% higher LDL-C levels and 7% higher HDL-C levels than strict vegetarians. Analysis within and among vegetarian populations suggests that ingestion of fatty dairy products raises the LDL-C level on a percentage basis about three times more than it raises the HDL-C level. PMID- 4021013 TI - Immune thrombocytopenia following alpha-interferon therapy in patients with cancer. AB - Immune thrombocytopenia occurred in five patients with cancer receiving alpha interferon. The median pretreatment platelet count was 217,000/cu mm, which fell to a median of 12,000/cu mm after a median of 25 days of interferon therapy. All had normal numbers of megakaryocytes, with dysplasia noted in three; all four who were tested had platelet-associated immunoglobulin. All had normalization of platelet counts with prednisone therapy. Four tolerated re-treatment with interferon, two with concurrent prednisone administration and two others following splenectomy. Immune thrombocytopenia should be considered in patients who become thrombocytopenic during interferon therapy. PMID- 4021014 TI - Closing the gap. Report of the Carter Center Health Policy Consultation. PMID- 4021015 TI - Closing the gap: the burden of unnecessary illness. PMID- 4021016 TI - Why the Carter Center? PMID- 4021018 TI - Late appearance of postpartum eclampsia. PMID- 4021017 TI - Public health problem of violence receives epidemiologic attention. PMID- 4021019 TI - Retinoic acid embryopathy: timing of exposure and effects on fetal development. PMID- 4021020 TI - Stadol dependence: another case. PMID- 4021021 TI - Laser angioplasty. PMID- 4021022 TI - Herpes zoster: adenosine monophosphate for the prevention of post-neuralgia. PMID- 4021023 TI - IgA deficiency and AIDS. PMID- 4021025 TI - Differential effects of exercise on serum lipid and lipoprotein levels seen with changes in body weight. A meta-analysis. AB - Ninety-five studies conducted between September 1955 and October 1983 measuring changes in human serum lipid and lipoprotein levels in response to exercise training were analyzed using meta-analysis. Change in body weight during exercise training may confound observed serum lipid and lipoprotein level changes; thus, data from these studies were partitioned into those where subjects gained body weight, maintained body weight, or lost body weight. Results showed differential changes in cholesterol, triglyceride, low-density lipoprotein-cholesterol (LDL C), high-density lipoprotein-cholesterol, and cholesterol/high-density lipoprotein-cholesterol levels in the three body-weight categories. Where body weight did not change, cholesterol and LDL-C levels decreased significantly (7.3 mg/dL and 3.3 mg/dL, respectively). Where body weight decreased, cholesterol and LDL-C levels also decreased significantly (13.2 mg/dL and 11.1 mg/dL, respectively). However, with body-weight increase, cholesterol and LDL-C levels increased by 2.9 mg/dL and 3.0 mg/dL, respectively. These results suggest that reductions in cholesterol and LDL-C levels were greatest when exercise training was combined with body-weight losses. PMID- 4021024 TI - Suicide and family loading for affective disorders. AB - All suicides were ascertained for a 100-year period (1880 to 1980) in a study of mental illness among the Old Order Amish. The majority (92%) of the 26 cases were diagnosed with a major affective disorder and were situated in multigenerational families with heavy loading for bipolar, unipolar, and other affective-spectrum illnesses. The suicides clustered in four primary pedigrees, and the role of inheritance was suggested by the way in which suicides followed the distribution of affective disorders in these kinship lines. We believe these extended pedigrees provide presumptive evidence of genetic factors in both suicides and affective disorders. PMID- 4021026 TI - Health and health services in Central America. AB - Despite rapid economic growth since World War II, health conditions improved only slowly in most of Central America. This is a result of poor medical, social, and economic infrastructure, income maldistribution, and the poor utilization of health investments. The economic crisis of the 1980s and civil strife have further endangered health in the region. Life expectancy has fallen among men in El Salvador and civil strife has become the most common cause of death in Guatemala, Nicaragua, and El Salvador. Large-scale US assistance has done little to improve conditions, and refugees continue to pour into North America. It is estimated that there are more than a million refugees within Central America, while a million have fled to the United States. Costa Rica and Nicaragua are partial exceptions to this dismal health picture. An effective approach to the many health problems in Central America will require joint planning and cooperation among all countries in the region. PMID- 4021027 TI - Chilaiditi's syndrome. Report of three cases. PMID- 4021028 TI - Pemoline abuse. AB - Addictive use of the stimulant drug pemoline caused a delusional disorder in a middle-aged man. Discontinuance of use of the drug promptly reversed the psychosis, which subsequently recurred when pemoline was again used. Pemoline seems to be an addictive drug and has an additional property that heretofore has been attributed mainly to amphetamines--precipitation of a paranoid psychosis. PMID- 4021029 TI - Purulent pericarditis and mediastinitis due to Peptococcus magnus. PMID- 4021030 TI - Acute ischemic optic neuropathy. PMID- 4021031 TI - Retrograde fallopian tube transport. PMID- 4021032 TI - Localized, sustained-release drug delivery uses membrane "envelope". PMID- 4021034 TI - Randomized clinical trials. PMID- 4021033 TI - From the NIH. Magnetic device tests for iron overload. PMID- 4021035 TI - Geographic pattern of Hodgkin's disease in the United States. PMID- 4021036 TI - Guidelines for handling parenteral antineoplastics. PMID- 4021037 TI - MAST suits. PMID- 4021038 TI - Female-to-male transmission of AIDS. PMID- 4021039 TI - Bubble Boy. PMID- 4021040 TI - Recurrent mucoceles. PMID- 4021041 TI - Three-wheeler accidents. PMID- 4021042 TI - Commercial hair analysis. Science or scam? AB - Hair samples from two healthy teenagers were sent under assumed names to 13 commercial laboratories performing multimineral hair analysis. The reported levels of most minerals varied considerably between identical samples sent to the same laboratory and from laboratory to laboratory. The laboratories also disagreed about what was "normal" or "usual" for many of the minerals. Most reports contained computerized interpretations that were voluminous, bizarre, and potentially frightening to patients. Six laboratories recommended food supplements, but the types and amounts varied widely from report to report and from laboratory to laboratory. Literature from most of the laboratories suggested that their reports were useful in managing a wide variety of diseases and supposed nutrient imbalances. However, commercial use of hair analysis in this manner is unscientific, economically wasteful, and probably illegal. PMID- 4021043 TI - Breast cancer prediction and the Wolfe classification of mammograms. AB - Mammographic parenchymal patterns have been proposed as a method of determining women at high risk of developing breast cancer. Wolfe's original report of relative risks as high as 37:1 for "dysplastic" breasts (DY) as compared with adipose breasts (N1), with intermediate values of P1 and P2, were not uniformly confirmed by others. (Relative risks are used here as the equivalent of odds ratios.) A case-control study of 706 breast cancers, each with two matching controls, drawn from 40,000 participants in four Breast Cancer Detection Demonstration Project clinics, was conducted to assess the role of the Wolfe classification of breast parenchymal patterns as a breast-cancer risk factor together with a set of well-established risk factors for breast cancer. Relative risks of 3.1 for DY to N1, 3.5 for P2 to N1, and 2.0 for P1 to N1 were determined. These are comparable to or greater than other known risk factors found in the same population. The Wolfe classification of parenchymal patterns strengthens the basis for clinical judgment, but should not be used exclusively to determine intervention in an individual patient's care. PMID- 4021045 TI - The town meeting for technology. The maturation of consensus conferences. PMID- 4021044 TI - Percutaneous nephrostolithotomy vs open surgery for renal calculi. A comparative study. AB - To evaluate the impact of the percutaneous removal of renal calculi we compared 41 patients who had undergone open renal surgery to 88 patients who had a one- or two-stage percutaneous nephrostolithotomy for symptomatic urolithiasis. The two groups were similar with regard to stone size, stone location, treatment success, and complication rates. However, for patients with calculi 2.5 cm or smaller in diameter, the percutaneous procedure resulted in lower postoperative morbidity, more rapid convalescence, less hospital cost, and greater patient satisfaction. For patients with calculi larger than 2.5 cm in diameter, the percutaneous approach was slightly more expensive than open surgery but resulted in a markedly shortened convalescent period. In our experience, percutaneous nephrostolithotomy performed in a single stage under assisted local anesthesia was the most efficacious and least expensive of the percutaneous approaches. PMID- 4021046 TI - Consensus conference. Anesthesia and sedation in the dental office. PMID- 4021047 TI - Consensus or coercion. PMID- 4021048 TI - Causes of, therapies for insomnia, other sleep problems under study. PMID- 4021050 TI - Leads from the MMWR. Alcohol-associated premature mortality--United States, 1980. PMID- 4021049 TI - Chronic insomnia: multidimensional in cause. PMID- 4021052 TI - Leads from the MMWR. Birthweight-specific neonatal mortality rates--Kentucky. PMID- 4021051 TI - Leads from the MMWR. Dinitrotoluenes in the workplace. PMID- 4021053 TI - Leads from the MMWR. Imported dengue fever--United States. PMID- 4021054 TI - Predicting outcome from hypoxic-ischemic coma. PMID- 4021055 TI - Problematic prostatic prediction. PMID- 4021056 TI - Physicians poor at prevalence and positive predictive value. PMID- 4021057 TI - Improved detection of early iron deficiency. PMID- 4021058 TI - Nifedipine-induced hypotension and myocardial ischemia in refractory angina pectoris. PMID- 4021060 TI - Delaying the diagnosis of disease. PMID- 4021059 TI - Autoimmune hemolytic anemia with both cold and warm autoantibodies. PMID- 4021061 TI - Physiologic and psychological characteristics associated with deaths due to asthma in childhood. A case-controlled study. AB - Several reports have documented characteristics of children who die of asthma; however, to the best of our knowledge, no studies have used case controls to clarify the clinical characteristics associated with death. We conducted a case controlled study of 21 patients with severe asthma hospitalized between 1973 and 1982 who died of asthma sometime following discharge. Average age at death was 13 years (range, 8 to 18 years). Twenty-one asthmatic control cases were matched for age at the time of hospitalization, sex, and severity of illness. Hospital records were evaluated for 57 physiologic and psychological variables. A stepwise discriminant analysis determined that the following eight variables could discriminate the two groups effectively: history of seizures associated with an asthma attack; conflicts between the patient's parents and hospital staff regarding medical management of the patient; self-care of asthma while in the hospital that was not appropriate for age; prednisone dosage having been decreased by more than 50% during the course of hospitalization; inhaled beclomethasone dipropionate required for treatment; increased asthmatic symptoms during the week preceding discharge; depressive symptoms; and disregard of asthmatic symptoms. Most of the clinical characteristics previously thought to place patients at greater risk for a fatal asthmatic attack were found as often in the control cases as in the children who died. This study indicates that psychologic risk factors were prominent in severely asthmatic children who subsequently died of asthma. The variables defined in this study may be important in identifying patients who are at high risk for dying of asthma and in developing treatment plans to prevent deaths. PMID- 4021062 TI - Infective endocarditis. Olmsted County, Minnesota, 1950 through 1981. AB - Strict criteria were used to identify all definite, probable, and possible cases of endocarditis in residents of Olmsted County, Minnesota, from 1950 through 1981. The mean annual age- and sex-adjusted incidence rates per 100,000 person years were 3.8 for total cases and 3.2 for definite and probable cases only. Total rates were 4.3 for 1950 through 1959, 3.3 for 1960 through 1969, and 3.9 for 1970 through 1981. Rheumatic heart disease was the underlying disorder in 26% of cases, with a shift noted during 1970 through 1981 to involvement of prosthetic rather than natural valves in these patients. Mitral valve prolapse was identified in 17% of cases. No source of infection could be identified in 41% of cases, including half of those cases with rheumatic or congenital heart disease. In cases diagnosed prior to autopsy, the 60-day fatality fell from 46% during 1950 through 1959 to 22% and 26% during 1960 through 1969 and 1970 through 1981, respectively. PMID- 4021063 TI - Predicting the outcome from hypoxic-ischemic coma: medical and ethical implications. PMID- 4021064 TI - Anisotropic conduction properties of canine ventricular muscles. Influence of high extracellular K+ concentration and stimulation frequency. AB - The effects of fiber direction on the conduction of excitation and the characteristics of both extracellular and intracellular action potentials were examined in isolated dog ventricular muscle preparations. Conduction velocity and amplitude of extracellular potentials during propagation in the direction parallel to the long axis of fibers (longitudinal propagation) were significantly greater than those during propagation in the direction perpendicular to it (transverse propagation). However, the maximum rate of rise and amplitude of intracellular action potential were significantly greater during transverse propagation than during longitudinal propagation. Compared with the transverse propagation, the longitudinal propagation was more susceptible to conduction failure under high extracellular K+ concentration, suggesting a lower safety factor of the latter mode of propagation in depolarized cardiac tissue. In contrast, high frequency stimulation caused a greater decrease in the conduction velocity during transverse than longitudinal propagation resulting in augmentation of anisotropic conduction properties. These results suggest that the anisotropic conduction properties of cardiac tissue may play important roles in conduction disturbances leading to arrhythmias under various pathological conditions. PMID- 4021065 TI - Recent trend of chemotherapy for infective endocarditis in Japan. AB - Out of the 10 patients with infective endocarditis (IE) at Kawasaki Municipal Hospital, 8 had IE due to streptococcus viridans. Out of 8 patients with streptococcus IE, 6 were successfully treated with benzyl penicillin alone or in combination with kanamycin. One patient was cured with cephaloridine. Two hundred and thirty IE patients admitted to hospitals at Kantou District were also studied. Ninety nine of 116 patients with streptococcus viridans IE were successfully treated with potentially active in vitro against streptococcus viridans. Out of 16 staphylococcus IE patients, 11 patients died. Eight patients died within 8 days from the beginning of the antibiotic administration. Out of 7 enterococcal IE patients, 5 were successfully treated with ampicillin alone or in combination with aminoglycosides. Forty three patients were diagnosed as IE despite negative blood culture. The echo cardiogram showed 23 patients had vegetation. Benzyl penicillin was given to 28 patients and 23 were cured. Out of 9 patients with culture negative IE treated with ampicillin, 8 were cured. Four patients were successfully treated with cephems. PMID- 4021066 TI - Medical management of infective endocarditis; limitations and indication for surgery. AB - Problems and limitations of medical management for infective endocarditis were studied and surgical indications were discussed based on the retrospective analysis of 55 episodes. Since perioperative complications still occur during highly active infection, antibiotic treatment was suggested as the primary management. Intractable or progressing heart failure appeared to be a definite indication for emergency surgery, but medical therapy was recommended for mild to moderate heart failure. For uncontrolled infection of more than one month duration despite the best available antibiotics, surgical debridement of the infected tissue was indicated. Occurrence of peripheral or fatal emboli was difficult to predict from clinical features and echocardiogram and therefore presented a therapeutic dilemma. Since major or fatal emboli frequently occurred during highly active infection, early initiation of effective antibiotic therapy was considered to be of primary importance. Demonstration of vegetation by echocardiography alone did not seem to justify urgent surgery. In addition, disseminated intravascular coagulation appeared to be a serious complication and thus sedimentation rate should be followed carefully. In the healed stage, prophylactic surgery seemed unnecessary for prevention of recurrent infection or embolization, as they were relatively rare. PMID- 4021067 TI - Infective endocarditis in children. AB - The clinical manifestations, infective microorganisms, underlying diseases, complications and prognosis of infective endocarditis (IE) were studied in 17 current patients. Data were compared with 101 previous cases reported in Japan. Most patients with IE (110/118 = 93.2%) had underlying heart diseases. IE was noted most often in patients with ventricular septal defect (VSD) and tetralogy of Fallot. The incidence of post operative endocarditis was high (29.4% in the present series and 9.0% in the overall series), too. Streptococcus viridans, Staphylococcus aureus and GNB were the most common etiologic agents with incidences of 28.8% (34/118), 25.4% (30/118) and 9.3% (11/118), respectively. Almost half of the deaths from IE were caused by s. aureus. The mortality was 11.9% (14/118) in both series. The death rate from candida albicans was 100%, from s. aureus 33.3% (10/30) and from str. viridans 5.9% (2/34) in both series. Culture negative patients accounted for 11.9% (14/118) in both series. Complications which did not involve the valves were noted in one patient with cerebral emboli and in two patients with pulmonary infarction in the present series. Cerebral emboli phenomena were seen 8 cases of the overall series, 4 of whom died. PMID- 4021068 TI - Surgical treatment for infective endocarditis--decision tree for the treatment and introduction of translocation method. AB - Persistent fever during active-phase IE is an indication for surgical treatment in the light of the causative organism and the underlying disease. To counter worsening hemodynamics, surgery may be the only feasible way. Surgery is performed when the patient does not respond to vasodilators and he shows an FS of less than 25%. The introduction of translocation provides a solution for the treatment of active IE. Lesions, vegetations more than 5 mm in diameter, periannular abscess, and mycotic aneurysm that could never be overlooked by two dimensional echocardiography may hasten the early-stage decision of ways to treat IE. PMID- 4021069 TI - Infective endocarditis, present status and problems on surgical treatment. PMID- 4021070 TI - [The study on the effect of spinal function in NLA--as an index of the change in unit activities on lamina V type cells]. PMID- 4021071 TI - [The effect of a high dose of vitamin E on the oxygen injured lung]. PMID- 4021072 TI - [Effects of endotoxin on rat erythrocyte membrane fluidity]. PMID- 4021073 TI - [Changes of P50 during open heart surgery]. PMID- 4021074 TI - [The cardiovascular effect of buprenorphine in dogs and open heart surgery patients]. PMID- 4021076 TI - [Normal range of intraocular pressure during enflurane anesthesia in children]. PMID- 4021075 TI - [The effect of halothane anesthesia on the ischemic liver]. PMID- 4021077 TI - [Epidural administration of morphine-droperidol mixture for postoperative analgesia]. PMID- 4021078 TI - [A statistical analysis of block therapy for hemifacial spasm]. PMID- 4021079 TI - [Treatment of herpes zoster]. PMID- 4021080 TI - [The effect of halothane and enflurane on liver and renal function in patients with liver cirrhosis]. PMID- 4021081 TI - [Perioperative management of open heart surgery for a low body weight (1,496 g) infant]. PMID- 4021082 TI - [Anesthetic management of a patient with a dermatomyositis, malignancy and pulmonary dysfunction]. PMID- 4021083 TI - [The anesthetic management of a child with arteriovenous malformation of the vein of Galen]. PMID- 4021084 TI - [Present status of manpower. (2) Means of increasing the supply of anesthesiologists to clinical anesthesiology departments]. PMID- 4021085 TI - [The effects of premedication on urinary catecholamine excretion in the young and elderly patients undergoing surgery]. PMID- 4021086 TI - [Exercise testing for evaluating the preoperative conditions of general surgical patients]. PMID- 4021087 TI - [Effects of fentanyl and morphine on hemodynamics and metabolism of rat heart after ischemia]. PMID- 4021088 TI - [Effects of amrinone on hemodynamics, oxygen consumption and plasma catecholamine levels in anesthetized dogs]. PMID- 4021089 TI - [Increased conjugated catecholamines in urine and blood after removal of pheochromocytoma]. PMID- 4021090 TI - [Effects of halothane on the respiratory and circulatory changes in response to surgical stimulation]. PMID- 4021091 TI - [The relationship between preoperative pulmonary blood flow measured by lung perfusion scanning with 99mTc-MAA and values of PaO2 during one-lung anaesthesia]. PMID- 4021092 TI - [Effects of epinephrine on plasma potassium; their relations with the liver]. PMID- 4021093 TI - [High frequency jet ventilation during open bronchus in the pulmonary surgery]. PMID- 4021094 TI - [Application of simulated closed circuit anesthesia and hydrogen accumulation in the circuit]. PMID- 4021095 TI - [Prevention of bacterial contamination of epidural catheters by an improved skin care technic]. PMID- 4021096 TI - [Changes in heart rate and blood pressure during epidural tap]. PMID- 4021097 TI - [Cardiovascular changes in terminal stage]. PMID- 4021098 TI - [General anesthesia for caesarean section in a patient with acute intermittent porphyria and psychogenic reaction]. PMID- 4021099 TI - [Anesthesia for a patient with 4P-syndrome]. PMID- 4021100 TI - [Past, present, future use of blood substitutes and plasma substitutes in Japan]. PMID- 4021101 TI - [Autotransfusion]. PMID- 4021102 TI - [CT and pathologic studies on detecting hepatic involvement of malignant lymphoma]. AB - In order to determine the value of CT in detecting lymphomatous involvement of the liver, 57 autopsied cases (48 cases of non-Hodgkin lymphoma and 9 of Hodgkin's disease) were analyzed in detail. Additionally, 90 recent cases of abdominal CT with liver study in the initial staging were reviewed and 6 cases in which the liver had been examined within 2 weeks before autopsy were compared for macroscopic and pathologic findings. The following results were obtained. Autopsy findings in 57 cases of malignant lymphoma. (1) Hepatic involvement was demonstrated in 56% of the patients with non-Hodgkin lymphoma and in 67% of those with Hodgkin's disease. Of these patients with hepatic involvement, intrahepatic nodular lesions over 1.0 cm in diameter were macroscopically identified in 22% of the cases of non-Hodgkin lymphoma and 33% of those with Hodgkin's disease. Lymphomatous involvements were seen in many organs in the cases of hepatic involvement. CT examinations of 90 cases for the initial staging showed no significant abnormality in the liver or spleen. Of the 6 cases in which the liver was examined by CT within about 2 weeks before autopsy, lymphomatous involvement was pathologically diagnosed in 5. Of these, only one having multiple nodules larger than the tip of a thumb was correctly diagnosed by CT. Hepatic involvement of lymphoma was thought to be the end stage, and minimal or early disease was detected in the region of Glisson's capsule. The above findings indicate that early hepatic involvement is not likely to be detected by CT at the present time. PMID- 4021104 TI - [Hematogenous metastasis in pancreatic cancer]. AB - Out of 248 pancreatic cancer patients, 82 with hematogenous metastases were clinicopathologically analyzed. The incidence of hematogenous metastases on laparotomy were 31% in the liver, 1.2% in the lung, and 0.4% in the adrenal gland and navel. The incidence of liver metastasis, which was present in 23% and 46% of the patients with carcinoma of the head of the pancreas and of the body and tail of the pancreas, respectively, was higher than that of carcinomas of the other digestive organs. In the autopsy findings of the cases submitted to tumor resection, early metastases to the liver, lung, cerebellum and ovary were recognized to have occurred postoperatively. A higher rate of liver metastasis with lymph node involvement in the early stage of the disease was peculiar to pancreatic cancer. PMID- 4021103 TI - [Treatment of small liver cancer]. AB - Histopathological studies were conducted on the resected lesions in eight cases of small liver cancer, and therapeutic methods are discussed. Examinations revealed tumor cell infiltration into the fibrous capsule in 5/7 (71%), into extracapsular tissues in 3/7 (43%), and vascular invasion by tumor cells in 2/8 (25%) cases. Seven patients were complicated with liver cirrhosis and one patient with hepatic fibrosis. On the basis of preoperative TAE performed in three cases and studies on the resected indicating that tumor cells remained that have infiltrated into extracapsular areas, resection was considered to be necessary to attain radical cure. At 100%, the one-year survival rate was encouraging. However, two cases of recurrence would suggest that further studies are necessary on areas to be resected. PMID- 4021105 TI - [An autopsy case of sudden death by obstruction of the pulmonary artery in cardiac rhabdomyosarcoma]. AB - The patient was a 50-year-old man. Chest X-ray films showed a tumor shadow near the heart, which was diagnosed as carcinoma of the left lung. The patient's heart suddenly and unexpectedly stopped and he consequently died when his body was set in the right lateral position for operation on the left pulmonary tumor. A tumor measuring 6 X 3 X 3 cm was found in the region from the right ventricle to the pulmonary artery at autopsy. It was postulated that the tumor might have obstructed the pulmonary artery when the position of the patient's body was changed for surgery. A metastatic nodule was found in the left lung. The tumor was a rhabdomyosarcoma, the pleomorphic type. PMID- 4021106 TI - [A case of oral florid papillomatosis combined with gastroduodenal polyposis]. AB - A 49-year-old man developing numerous papillary or partly cauliflower-like tumors over the lips, oral angles, gingiva and tongue starting 15 years earlier and associated with multiple gastroduodenal polyps of various sizes revealed by X-ray examination is presented. Histologically, the oral lesions consisted of marked proliferation of mature squamous cells without appreciable cellular atypism or submucosal invasion. Electron microscopic study failed to detect any virus-like particles, and negative reaction was obtained in immunohistological study for papilloma virus. The association of gastroduodenal polyposis with oral florid papillomatosis has appeared very rarely in the literature. Although the relationship between the two lesions remains unknown, it was assumed in the present case that all lesions would represent an entity of a hamartomatous nature. PMID- 4021107 TI - [A case of multiple carcinomas of the colon and rectum associated with ulcerative colitis]. AB - The present paper describes a patient with four independent carcinomas associated with ulcerative colitis. Subtotal colectomy with lymph node dissection was done on June 28, 1978. The operative specimen revealed a carcinoma at the descending colon, two independent cancerous lesions and papillary polyps at the sigmoid colon and a scirrhous, flat elevated neoplasm at the rectum. These carcinomas were surrounded by lesions of various degrees of epithelial dysplasia, suggesting precancerous change. Carcinomas and precancerous lesions were stained for carcinoembryonic antigen (CEA) by the CEA peroxidase antiperoxidase method, which is considered to be useful to discriminate precancerous change from an inflamed mucous membrane. PMID- 4021108 TI - [Production of monoclonal antibodies against factor IX and their immunological characterization]. PMID- 4021109 TI - [Immunoradiometric assay of factor IX antigen using monoclonal antibody and classification of hemophilia B]. PMID- 4021110 TI - [Five children with hemolytic uremic syndrome--their clinical course and findings on the coagulation and fibrinolysis system]. PMID- 4021112 TI - [Progress in the study of infections]. PMID- 4021111 TI - [A case of autoimmune hemolytic anemia associated with ovarian dermoid cyst]. PMID- 4021113 TI - [Treatment of infection]. PMID- 4021114 TI - [Description of various types of infection]. PMID- 4021115 TI - [General outline of infections]. PMID- 4021116 TI - [Infections in various medical specialties]. PMID- 4021117 TI - [Theories concerning various infections]. PMID- 4021118 TI - A descriptive epidemiological study of hematopoietic neoplasms in Japan. AB - In 1982, the number of deaths from hematopoietic neoplasms was 5,885 for males and 4,237 for females, which corresponded to about 6% of all malignant neoplasms. The increase in the age-adjusted death rate in the last 10 years was highest for lymphatic leukemia (1.8 times), followed by multiple myeloma (1.7 times), malignant lymphomas (1.3 times) and myelogenous leukemia (1.1 times). In the old age group, i.e., over 70, the death rate for all types of hematopoietic neoplasms markedly during this period, particularly for multiple myeloma. In children, however, an increase in lymphatic leukemia and a decrease in decrease in myelogenous leukemia were observed. Geographical marked excess in the death rates for malignant lymphomas and lymphatic leukemia in the Kyushu district, especially in the middle- and old-age groups. This may be attributed to the high incidence of adult T-cell leukemia/lymphoma in the southwestern part of Japan. The age adjusted death rate for malignant lymphomas was slightly higher in rural areas than in urban areas in males in Kyushu. PMID- 4021119 TI - Preliminary phase II study of adriamycin (ADM) in patients with non-small cell lung cancer (NSCLC). AB - A phase II study of adriamycin (ADM) (60 mg/m2) was performed in 22 patients with non-small cell lung carcinoma (NSCLC). There were no responders in the 19 evaluable patients (16 with adenocarcinoma, two with squamous cell carcinoma and one with large cell carcinoma). The major side effects were alopecia (89%), leukocytopenia (73%), thrombocytopenia (58%) and upper gastrointestinal symptoms. Although ADM at 60 mg/m2 did not appear to have sufficient antitumor activity against NSCLC in this study, it is necessary to evaluate further the efficacy of ADM against NSCLC with another treatment schedule. PMID- 4021120 TI - One-hundred-and-two 5-year survivors of esophageal carcinoma after resective surgery. AB - Among 492 patients with esophageal carcinoma who received resective surgery, 102 survived over 5 years. These 5-year survivors were analyzed according to many factors. Females had a better prognosis than males, and patients without lymph node metastasis had a better 5-year survival rate than those with it. Ten patients who survived over 5 years had recurrences and received therapy. As a cause of death after 5 years, double primary carcinoma of other organs is more frequent than recurrence. PMID- 4021121 TI - Latitude and pancreatic cancer. AB - With regard to the geographical distribution of pancreatic cancer mortality, the relationship of the latitude and of the average temperature to pancreatic cancer mortality was examined. Both internationally and within Japan, a strong positive association between latitude and pancreatic cancer mortality and a strong negative association with the average temperature were observed. The simple correlation coefficient between pancreatic cancer mortality and the latitude was 0.724 for males and 0.725 for females, and that between pancreatic cancer mortality and the average temperature was -0.773 for males and -0.729 for females in 26 countries. In the 47 prefectures in Japan, the coefficient was 0.612, 0.615, -0.589, and -0.630 respectively. Most of these relationships remained statistically significant after controlling for per capita consumption of food which was also related to the pancreatic cancer mortality internationally, such as sugar, eggs, milk and dairy products, oils and fats, pulse, coffee, and fat. Within Japan, an urban-rural effect on the pancreatic cancer mortality was not observed in spite of a higher intake of fat in large cities. There remains the possibility that factors related to latitude or average temperature other than diet may be involved in the occurrence of pancreatic cancer. PMID- 4021122 TI - Second primary malignancies in lymphoma patients. AB - We evaluated the occurrence and the type of second malignancies among 74 patients with Hodgkin's disease (HD) and 407 patients with non-Hodgkin's lymphoma (NHL) who were treated at the National Cancer Center Hospital for more than one year. Fifteen patients developed a second malignancy. In 10 of these patients the second cancer was gastric cancer, but no cases of acute nonlymphocytic leukemia were encountered. The observed number of second cancers in females among the HD patients was significantly (p less than 0.005) greater than the expected incidence based upon the number of age-adjusted person-years both for all cancers and for stomach cancer. However, no significant differences between males and females in the NHL patients were found. Furthermore, no significant differences were seen in any of the groups between the observed and expected numbers of second malignancies according to the treatment. PMID- 4021123 TI - Juvenile secretory carcinoma and juvenile papillomatosis. AB - Two cases of juvenile secretory carcinoma associated with juvenile papillomatosis are reported. One patient's disease was initially diagnosed at the age of 13 and she died 12 years later with extensive metastases. The contralateral breast at autopsy showed findings indicative of juvenile papillomatosis. The second case is that of an 18-year-old girl who had multiple juvenile secretory carcinomas in the left breast associated with juvenile papillomatosis. PMID- 4021125 TI - [Magnetic resonance imaging of spinal diseases]. PMID- 4021124 TI - [Magnetic resonance imaging in craniovertebral junction anomaly]. PMID- 4021126 TI - [Combined use of intraarterial digital subtraction angiography with conventional retrograde brachial vertebral angiography]. PMID- 4021128 TI - [CT images of anomalies of the mediastinal vessels--differentiation from mediastinal lymphadenopathy]. PMID- 4021127 TI - [X-ray diagnosis of type IIb early gastric cancer]. PMID- 4021129 TI - [Computed tomography in anomalies of thoracic aortic arch]. PMID- 4021130 TI - [Simple cysts of the kidney and aging]. PMID- 4021131 TI - [Radiological study of immunoblastic lymphadenopathy]. PMID- 4021132 TI - [Localized bilateral empyema caused by spontaneous esophageal rupture]. PMID- 4021133 TI - [Adrenomedullary scintigraphy with I-131 metaiodobenzylguanidine]. PMID- 4021134 TI - [A case of shock by pretesting of contrast media]. PMID- 4021135 TI - [A case of esophageal cyst located at middle mediastinum]. PMID- 4021136 TI - [A case report of cavernous transformation of the portal vein with liver abscess]. PMID- 4021137 TI - [A case report of successful control of traumatic bleeding by superselective transcatheter embolization in the solitary kidney]. PMID- 4021138 TI - [A case of giant cell tumor of the ischium]. PMID- 4021139 TI - [Translumbar aortography utilizing long elaster needle and J-guide wire]. PMID- 4021140 TI - [Transnasal permanent interstitial implantation for recurrent carcinoma of the nasopharynx]. PMID- 4021141 TI - [The lung disease of RA patients]. PMID- 4021142 TI - [Usefulness of computed tomography in discrimination of thymoma]. PMID- 4021143 TI - [Angiography of Wegener's granulomatosis]. PMID- 4021144 TI - [Hepatic artery embolization using balloon catheters]. PMID- 4021145 TI - [Diagnosis of adrenal adenoma and hyperplasia by CT and adrenal scintigraphy]. PMID- 4021146 TI - [A case of pulmonary actinomycosis]. PMID- 4021147 TI - [Computed tomographic demonstration of azygos continuation with the left inferior vena cava]. PMID- 4021148 TI - [A complicated case of Morgagni's hernia and Bochdalek's hernia, with special reference to CT examination]. PMID- 4021149 TI - [A case of simultaneous triple cancer]. PMID- 4021150 TI - [A case of progressed gastric cardial carcinoma survived for more than 8 years treated with 3000 rad of radiation and peroral 5-FU]. PMID- 4021151 TI - [A case of necrotic renal cell carcinoma with abscess formation]. PMID- 4021152 TI - [Prone position intravenous digital subtraction angiography of the pelvis]. PMID- 4021154 TI - [A new device for percutaneous transhepatic biliary endoprosthesis]. PMID- 4021153 TI - [Dynamic CT examination with iopamidol]. PMID- 4021155 TI - [Studies of contact hypersensitivity and immune tolerance in experimental neoplasms]. PMID- 4021156 TI - [The 84th annual meeting of Japanese Dermatological Association. Okayama, Japan, April 12-14, 1985. Abstracts]. PMID- 4021157 TI - [Effects of sunscreens and their bases on UV-transmission in porcine skin]. PMID- 4021158 TI - [Clinical, histopathological and ultrastructural characteristics of dysplastic melanocytic nevus in comparison to cutaneous malignant melanoma--II: Ultrastructural characteristics of melanocytes and melanosomes]. PMID- 4021159 TI - [Effects of colchicine on stroma cells in a patient with tuberous sclerosis]. PMID- 4021160 TI - [Content of eumelanin and pheomelanin in malignant melanoma tissues in the Japanese]. PMID- 4021161 TI - [Cytodiagnosis of malignant melanoma by the formaldehyde-induced fluorescence method]. PMID- 4021162 TI - [A comparative study on the effect of vagotomy and splanchnicectomy on the catecholamine content of the stomach, duodenum and pancreas]. PMID- 4021163 TI - [Investigation of endogenous prostaglandins in DMH induced colonic cancer in rats]. PMID- 4021164 TI - [Plasma fibronectin in inflammatory bowel disease]. PMID- 4021165 TI - [Studies on hepatocellular injury in experimentally induced acute hepatic failure -I. Possible involvement of the activated adherent cells]. PMID- 4021166 TI - [Effective oral doses of propranolol, and endoscopic findings on the effects of propranolol on esophageal varices]. PMID- 4021167 TI - [The sphincter mechanism of the choledochoduodenal junction following truncal vagotomy]. PMID- 4021168 TI - [Clinical evaluation of endoscopic retrograde biliary drainage (ERBD) in comparison with that of precutaneous transhepatic biliary drainage (PTBD)]. PMID- 4021169 TI - [Effect of gastrin releasing peptide on exocrine pancreatic secretion and plasma levels of CCK and PP in conscious dogs]. PMID- 4021170 TI - [A case of adenocarcinoma arising from Barrett's esophagus]. PMID- 4021172 TI - [The 71st congress of the Japanese Society of Gastroenterology. Sapporo, Japan, May 22-24, 1985. Abstracts]. PMID- 4021171 TI - [A case of mucin-producing pancreas carcinoma]. PMID- 4021173 TI - [Proceeding of the 55th annual meeting of the Japanese Society for Hygiene. Kumamoto, Japan, April 2-4, 1985. Abstracts]. PMID- 4021174 TI - IgE antibody against hepatitis B surface antigen in mice. AB - Hepatitis B surface antigen (HBs antigen) was examined for elicitation of IgE production by injection into mice. The Prausnitz-Kustner (PK)-type skin test in the rat was employed for detection of IgE antibody to HBs antigen, because no sufficient purified HBs antigen was available as the challenging antigen for the passive cutaneous anaphylaxis (PCA) test in rats. The positive PK test was considered to be due to IgE antibody, since the active principle was inactivated by heating the sera at 56 C for 30 min, did not bind to protein A and was eliminated by anti-mouse IgE antisera. These data indicate that the PK-type test in rats can be used for detection of mouse IgE antibody when the amount of a test sample is not sufficient for the PCA test in rats. PMID- 4021175 TI - Exploitation of genetic markers in laboratory animals--with specific reference to the rat. PMID- 4021176 TI - Blood-protein variations within and between macaque species. PMID- 4021177 TI - Molecular evolution of non-human primates--hemoglobins of macaque monkeys. PMID- 4021178 TI - Use of genetic markers in the management of captive groups of rhesus monkeys at the California Primate Research Center, U.S.A. PMID- 4021179 TI - Genetic control of the cynomolgus monkey breeding colony by the use of blood groups. PMID- 4021180 TI - Potency test of hepatitis B vaccines by the parallel line assay method in mice. AB - Adequate conditions for the potency test of hepatitis B (HB) vaccines in mice were looked for. Preliminary tests showed that BALB/c female mice of 5 weeks of age are adequate for the test. An immunization period of 5 weeks was found satisfactory for the test. Under these conditions, mice were immunized with each of serial dilutions of the test vaccine and a reference vaccine. The use of the parallel line assay method and the expression of the potency relative to that of the reference vaccine gave a reliable estimate of the potency of HB vaccine. PMID- 4021181 TI - [Antibody-dependent cell-mediated cytotoxicity in primary glomerular diseases]. PMID- 4021182 TI - [Correlation of postheparin hepatic triglyceride lipase activity to serum intermediate density lipoprotein and triiodothyroxine levels in patients on maintenance hemodialysis]. PMID- 4021183 TI - [Determination of polyamines in plasma and erythrocytes of patients with chronic renal failure]. PMID- 4021184 TI - [A case of common variable immunodeficiency associated with chronic hemodialysis]. PMID- 4021185 TI - [Antinephritic effect of trimetazidine on nephrotic-type and crescentic-type anti GBM nephritis in rats]. PMID- 4021186 TI - [Morphological studies on focal glomerular sclerosis (FGS) in rat--disturbance of glomerular polyanion]. PMID- 4021187 TI - [A histological study of idiopathic nephrotic syndrome--localization of IgM in the glomeruli]. PMID- 4021188 TI - [Two cases of sudden deafness in hemodialysis patients]. PMID- 4021189 TI - [Recurrent form of hemolytic-uremic syndrome in siblings]. PMID- 4021190 TI - [Role of renin-angiotensin system and prostaglandin system in the contralateral kidney of acute 2-kidney, 1 clip renovascular hypertension]. PMID- 4021191 TI - Low serum levels of IgG- and IgM-rheumatoid factors in patients with idiopathic membranous nephropathy. PMID- 4021192 TI - A case report of membranoproliferative glomerulonephritis type II with atypical intramembranous dense deposits. PMID- 4021193 TI - Concomitant therapy with prednisolone and cyclophosphamide in 17 cases with IgA nephropathy. PMID- 4021194 TI - Prognostic significance of mesangial sclerosis in IgA nephropathy. PMID- 4021195 TI - Effects of 1 alpha-hydroxyvitamin D3 on the skeletal muscle of uremic rats. PMID- 4021196 TI - Renal failure in sisters with cystinuria and the management of amino acids in chronic hemodialysis. PMID- 4021197 TI - Nucleus locus coeruleus (LC) in the prehypertensive stage of the deoxycorticosterone acetate (DOCA)-salt hypertensive rat (DHR). PMID- 4021198 TI - 2,8-Dihydroxyadenine urolithiasis induced by dietary adenine in rats. PMID- 4021199 TI - Usefulness of computerized tomography in the diagnosis of faintly opaque, very small renal calculi. PMID- 4021200 TI - Amelioration of albuminuria induced by dilazep administration in aminonucleoside nephrosis of rats. PMID- 4021201 TI - [Aerosol lung inhalation scintigraphy in normal subjects]. PMID- 4021202 TI - [Clinical evaluation of measurement of pancreatic enzyme synthesis activity in chronic pancreatitis]. PMID- 4021203 TI - [Thallium lung uptake images (TLI) in patients with acute myocardial infarction]. PMID- 4021204 TI - [Studies on the diagnosis of uterine body cancer using 201Tl-chloride]. PMID- 4021205 TI - [Severity of coronary artery lesion by washout rate (WR) in exercise myocardial scintigraphy]. PMID- 4021206 TI - [Scintigraphic localization of metastatic pheochromocytoma by 131I metaiodobenzylguanidine]. PMID- 4021207 TI - [Fundamental studies of IgE kit "Daiichi" S]. PMID- 4021208 TI - Bile duct lesions and diminution in number of intrahepatic bile ducts in asymptomatic primary biliary cirrhosis. AB - Morphological changes of interlobular bile ducts in asymptomatic or symptomatic primary biliary cirrhosis (PBC) and chronic hepatitis with ductal lesions were investigated. It was supposed that bile duct lesions found in PBC and chronic hepatitis could be distinguished histologically. There were identical epithelial changes between symptomatic PBC and asymptomatic one, but granulomas were more often found in asymptomatic PBC than in symptomatic PBC. Numbers of interlobular bile ducts per portal tract and the rates of portal tracts without interlobular duct in asymptomatic PBC were intermediate between symptomatic PBC and chronic hepatitis. Serial sections revealed that some bile ducts were able to be followed by ductules in asymptomatic PBC. From these results, numbers of interlobular bile ducts are undoubtedly decreased in asymptomatic PBC but not so much as in symptomatic one. This observation may be attributable partially for taking asymptomatic course. PMID- 4021209 TI - Electrophysiological analysis of warming up phenomenon in myotonia. AB - The after discharges following grip and percussion in myotonia of 4 cases with myotonic dystrophy were evaluated in repetitive percussion or grip, in cold exposure and in warm exposure electromyographically. By repetition, the after discharges reduced markedly. After 2 or 3 trials, after discharges disappeared or became short duration. During local cooling (15 degrees C-20 degrees C), the amplitude and the prolongation in the duration of after discharges were marked, although these enhanced after discharges were reduced by repetition even in cooling. During local warming (40 degrees C-42 degrees C), the after discharges became less marked or disappeared. Both the warming of muscle and the repetitive movements reduced the duration of abnormal after discharges. These effect might be explained on the same mechanism which was the change of the ion transport in muscle membrane, and could be called as warming up phenomenon together. The degree of these after discharges are close related to the degree of myotonic phenomenon. Myotonia is the disorder of primarily the electrical excitabilities, not the contractile properties. So the method of evaluation of after discharges electromyographically is very valuable compared to the measurement of the relaxation process which was used popular in evaluation of myotonia in the past. PMID- 4021210 TI - Possible participation of cholestatic factor in the pathogenesis of intrahepatic cholestasis in alcoholic liver disease. AB - To elucidate the immunopathogenesis of intrahepatic cholestasis in alcoholic liver disease, the authors investigated the possible participation of a cholestatic factor. The peripheral lymphocytes from patients with intrahepatic cholestasis in alcoholic liver disease were stimulated with ethanol and liver specific lipoprotein in vitro and the culture supernatant was fractionated by gel filtration, using a Sephadex G-75 column. When a definitive fraction (fraction 4) was injected into the mesenteric vein of rats, a marked reduction in bile flow was observed. Similar results were obtained when the blood serum of patients was fractionated in an identical manner and the same fraction was injected into rats via the mesenteric vein. Histologically, dilated bile canaliculi with diminution of microvilli and increased vesicles around the dilated canaliculi were observed by electron microscopy after injection of the active fraction into rats. These results strongly suggest that not only the sensitized lymphocytes produce the cholestatic factor which caused the intrahepatic cholestasis by specific stimulation, but also this factor is involved significantly in the pathogenesis of intrahepatic cholestasis which is observed in patients with intrahepatic cholestasis in alcoholic liver disease. PMID- 4021211 TI - Variability of breath-by-breath tidal volume and its characteristics in normal and diseased subjects. Ventilatory monitoring with electrical impedance pneumography. AB - To assess clinical significance of breath-by-breath variation of tidal volume and its distribution pattern displayed as a histogram, continuous measurement of tidal volume was made with electrical impedance pneumography for about 60 minutes. Subjects were composed of 26 normal male and 46 patients including 17 patients with restrictive lung disease and 29 patients with obstructive lung disease. To evaluate variation of tidal volume quantitatively, coefficient of variance (C.V.) was used. In comparison to the normal pattern of distribution (C.V. = 26.0 +/- 7.5%, mean +/- S.D.), patients with restrictive lung disease showed extremely narrow pattern of the distribution and significantly smaller C.V. (17.5 +/- 4.6% in old pulmonary tuberculosis, P less than 0.005 and 18.9 +/- 9.3% in pneumonitis, P less than 0.025). Whereas, patients with obstructive lung disease showed widespread pattern of the distribution and significantly greater C.V. (43.2 +/- 13.0% in pulmonary emphysema with hypercapnia, 33.0 +/- 7.5% in normocapnia and 35.8 +/- 9.4% in asthmatic attack, P less than 0.005). In all the patients with bronchial asthma after the treatment, the extremely widespread pattern of histogram was returned toward the normal one and the C.V. was decreased (22.4 +/- 6.4%). It was suggested that the distribution pattern of tidal volume was affected by the change of clinical condition, and was well correlated to the pathophysiological process related to restrictive or obstructive lung disease. We conclude that analysis of tidal volume distribution by the histogram is one of the useful approach to manage patients with respiratory diseases. PMID- 4021212 TI - A case of severe dehydration with marked rhabdomyolysis. AB - A 23-year-old male was admitted to hospital with severe dehydration and hypokalemic myopathy due to secondary aldosteronism. On admission serum sodium and chloride were markedly elevated to 198 mEq/l and 169 mEq/l, respectively, and serum potassium was down to 2.3 mEq/l. Serum electrolytes were normalized by transfusion therapy, but subsequently rhabdomyolysis grew worse due to metabolic abnormalities such as dehydration, hypothermia, oppressive ischemia and metabolic acidosis, at the same time transient polyuria and the elevation of serum myoglobin and enzymes originating in muscle tissue were observed. Serum CPK went up to 26,532 IU/l on the sixth day and other enzymes reached a peak following CPK. Dexamethasone was administered when the increase in enzyme levels caused the patient to fall into a stupor. He rapidly regained consciousness from the 15th day after admission, and he was able to stand up on the 29th day. Serum enzymes originating in muscle tissue decreased gradually to the normal range by the 30th day and no renal failure occurred. PMID- 4021214 TI - Expression to the host defense mechanism in the protection against microbial infections. PMID- 4021213 TI - A case of hepatic hydrothorax. AB - Hepatic hydrothorax occurred in a 38-year-old woman of severe hepatic failure complicated with pulmonary tuberculosis. The transdiaphragmatic passage of ascitic fluid to the pleural cavity was visually shown with a scintigram using technetium-99m macroaggregated albumin and also shown with a tracer analysis using indocyanine green. The ascites was suggested to be transported to the pleural cavity via the defect in the right diaphragm. PMID- 4021215 TI - Autonomic nervous contributions to the frequency of distension induced gastric motility in anesthetized dogs. AB - Changes in gastric motility induced by distension of the stomach were studied electromyographically in anesthetized dogs. In vagotomized dogs, gastric distension decreased the electrical control activity (ECA) frequency. The magnitude of this decrease was correlated with the degree of gastric distension; its' frequency decreased from 4.7 to 3.5 Hz/min with 400 ml distension. In splanchnicectomized dogs, 400 ml gastric distension also evoked a decrease in ECA frequency from 3.9 to 2.9 Hz/min. In vagotomized and spinal transected dogs, 400 ml distension of the stomach evoked a decrease in ECA frequency from 4.3 to 3.4 Hz/min. In the vagotomized and splanchnicectomized dogs, ECA frequency decreased from 5.0 to 3.4 Hz/min with 400 ml distension. These values were similar to those of the intact stomach previously reported. The results of the present study suggest that the extrinsic autonomic nervous system does not contribute significantly to regulation of the ECA frequency following gastric distension in anesthetized dogs. PMID- 4021216 TI - Selective blocking action of tetraethylammonium ion on three types of acetylcholine receptors in Aplysia ganglion cells. AB - The ganglion cells of Aplysia have three types of acetylcholine (ACh)-receptors in their membranes. The activation of one type produces Na+-dependent depolarization (DNa-type). The other receptors are HK- and HC1-types, the activation of which produces either K+- and Cl- dependent hyperpolarization, respectively. ACh-induced membrane current (IACh) was measured under the voltage clamp at different holding potential levels (V) of the membrane. The effects of tetraethylammonium (TEA) were analyzed quantitatively on each type of receptor activity by observing the changes in dose-inhibition curves and IACh-V relations obtained under voltage clamp. TEA exhibited a dose dependent block on both DNa- and HK-type of receptor activities but no effect on HCl-type. The mode of blocking action was found to be competitive in HK-type but noncompetitive in DNa type. In the DNa-type receptor, 3 mM TEA shifted the reversal potential of ACh induced current response from +5 to +40 mV, and caused a decrease in the slope of the IACh-V curve. In HK-type, TEA simply decreased the slope of IACh-V curve without changing the reversal potential of the ACh-induced response. It was concluded that TEA competed that with ACh for common binding sites at the receptor of the HK-type, but not of the DNa-type, and that in DNa-type, TEA made a binding with an allosteric site of the ACh-receptor and depressed the increase in membrane permeability toward Na+ as well as K+. PMID- 4021217 TI - Action of dantrolene sodium on electrical and mechanical activity of guinea-pig ventricular muscles. AB - Effects of dantrolene sodium on electrical and mechanical activity of guinea-pig ventricular muscles were examined. The application of 2 X 10(-5) M of dantrolene caused a decrease of developed tension by 31% of the control level without noticeable changes in resting membrane potential, amplitude and maximum upstroke velocity (Vmax) of action potentials, and action potential duration. Negative inotropic effects of dantrolene appeared after 10 min application and reached almost a plateau after 15-20 min. Neither amplitude of the slow inward current nor the outward current on depolarization were affected by dantrolene. When muscle preparations were superfused with the low-K+, high-Ca2+ solution, they developed delayed afterdepolarizations and aftercontractions. The application of 2 X 10(-5) M of dantrolene did not reduce amplitudes of both delayed afterdepolarizations and aftercontractions, but depressed twitch tension to 74% of the control level. Dantrolene did not change the amplitude of the transient inward current observed under the low-K+, high-Ca2+ condition. These results suggest that a primary site of action of dantrolene is not the sarcolemma of ventricular myocardium, but possibly the Ca2+ releasing process from the sarcoplasmic reticulum. Its action is further indicated to affect the process of depolarization-induced Ca2+-release, either directly or indirectly rather than to inhibit Ca2+-induced Ca2+-release. PMID- 4021218 TI - Vascular area with marked resistance elevation in one-clip, two-kidney renovascular hypertensive rats. AB - Blood flow in the terminal aorta or superior mesenteric artery was recorded in conscious one-clip, two-kidney renovascular hypertensive rats and normal control rats with a chronically implanted electromagnetic flow probe. An indwelling catheter for direct measurement of arterial pressure was inserted into the terminal aorta in rats with a flow probe around the superior mesenteric artery. In the hindquarter area supplied by the terminal aorta, the elevation of vascular resistance in hypertensive rats in relation to normal rats was close to the average over the whole body. However, it was about 40% more intense than the average in the superior mesenteric area. Quantitatively, the hindquarter and superior mesenteric beds in hypertensive rats contributed about a quarter and a third of the decrease in total vascular conductance, respectively. Plots of superior mesenteric flow per body weight against arterial pressure at rest for 51 measurements in 9 hypertensive rats revealed an inverse relation between these two variables. These findings indicate that elevation of vascular resistance in the superior mesenteric area and probably the splanchnic area in general play an important role in one-clip, two-kidney renovascular hypertension. PMID- 4021219 TI - Length dependent potentiation and inhibition of post-rest twitch tension development in adult cat and kitten papillary muscles. AB - If a rest interval is applied to a regularly stimulated cardiac muscle, the first contraction after this interval (post-rest contraction) has either a greater (post-rest potentiation) or a smaller (post-rest inhibition) developed tension than the regular contraction. Positive inotropic interventions will augment the post-rest potentiation and reduce the post-rest inhibition. We examined the effects of muscle stretching on the post-rest contraction in papillary muscles isolated from adult cats and from kittens and compared the effects with those of two typical inotropic interventions: high frequency stimulation and high calcium concentration. We found that muscle stretching augmented the post-rest potentiation and reduced the post-rest inhibition in a manner similar to the two inotropic interventions in the adult cat papillary muscle, and that these effects were consistently reversed in the kitten papillary muscle. The similarity of the effect of muscle stretching to those of the two typical inotropic interventions in either adult cat or kitten papillary muscle suggests that the effect of muscle stretching is due to an inotropic effect of muscle length change. PMID- 4021220 TI - Effects of intraventricular angiotensin II on heat balance at various ambient temperatures in rats. AB - Angiotensin II (AII, 5 micrograms) injected into the cerebral ventricles produced hypothermia in conscious rats at ambient temperatures (Ta) of 18, 23, and 28 degrees C. At Ta of 18 and 23 degrees C, AII-induced hypothermia was attributed to both enhancement of heat loss and suppression of metabolic rate. At Ta of 28 degrees C, AII-induced hypothermia seemed to be mainly attributed to increased heat loss. PMID- 4021221 TI - The influence of body size on the ventilatory response to hypercapnia. AB - The slope of ventilatory response to hypercapnia at rest was determined in 77 healthy male students by means of the CO2 rebreathing method. It was found that the hypercapnic ventilatory response slope (S) was significantly lower in the lean group with BMI (body mass index) below 19 than that in the normal group, while there were no significant correlation between S and body weight or height. These results indicate that sensitivity of hypercapnia in the lean subjects differed from that of normal and overweight subjects. PMID- 4021222 TI - Studies on exercise and an elastic protein "connectin" in hindlimb muscle of growing rat. AB - We examined the effect of physical training on the properties of an elastic protein, connectin, in the hindlimb muscles of 6 growing rats running on a treadmill, in comparison with its properties in 6 growing non-running rats. The experimental results are as follows. 1) The body weight of exercised (R-) and control (C-) rats gradually increased during housing for 31 days, from an average of 46.2 g to 275 g. The average amount of running in the 6 R-rats was 38,160 +/- 12,122 (S.D.) g X m/hr. 2) The SDS-insoluble connectin in R-rat muscle was lower in quantity than that in C-rat muscle, but the SDS-soluble connectin of R-rat muscle was greater in quantity. 3) Amino acid compositions of SDS-soluble connectin in R- and C-rats, calculated from SDS-insoluble connectin and soleus ghost, were significantly different. 4) The soleus ghost preparation consisted mainly of connectin as shown by SDS polyacrylamide gel electrophoresis and by immunohistological staining. 5) The maximum passive tension of the soleus ghost, calculated from the factors of T/phi and (dT/dx)/phi, was higher in R-rats than in C-rats. The above results suggest that physical training might alter the biosynthetic pattern of connectin to suit the developing muscle, just as physical training alters that of myosin isoenzymes. PMID- 4021223 TI - Mechanism of elevation of hindquarter vascular resistance in spontaneously hypertensive rats. AB - In spontaneously hypertensive rats and normotensive control rats in the conscious state, hindquarter flow was observed with an electromagnetic flow probe chronically implanted around the terminal aorta. In separate groups of hypertensive and control rats, arterial pressure was observed with an indwelling catheter inserted into the terminal aorta. On ganglion blockade with hexamethonium bromide, hindquarter flow tended to increase in hypertensive rats and to decrease in normal rats. The percent change of hindquarter flow on ganglion blockade was significantly greater in the former than in the latter (p less than 0.05). Hindquarter peripheral resistance, estimated from flow and pressure values obtained in separate rat groups, was greater in hypertensive rats than in normal rats before ganglion blockade, but there was no difference between the groups after blockade. Presumably, an elevated sympathetic tone is responsible for the higher hindquarter peripheral resistance in spontaneously hypertensive rats, which plays an important part in the elevation of total peripheral resistance. However, bilateral lumbar sympathectomy did not induce chronic lowering of arterial pressure in hypertensive rats. This was at least partly due to the development of denervation supersensitivity. PMID- 4021224 TI - An increase in cerebral blood flow elicited by electrical stimulation of the solitary nucleus in rats with cervical cordotomy and vagotomy. AB - The effect of monopolar electrical stimulation of the intermediate portion of the solitary nucleus (SOL) on brain circulation was investigated in 48 anesthetized (N2O), artificially ventilated Wistar rats. The cervical spinal cord and bilateral vago-sympathetic trunks were severed to eliminate any change in arterial blood pressure mediated by the autonomic nervous systems on stimulating the SOL. Blood pressure was kept within the physiological range by intravenous phenylephrine infusion. Current intensity of the stimulus was set at 60 +/- 4 microA (mean +/- S.E.; n = 9), which was equivalent to 2.5 times threshold for vasopressin-induced pressor response. A sufficient dose of vasopressin-antagonist given to each rat shortly before determination of cerebral blood flow, prevented vasopressin-induced hypertension from stimulating the medulla. Stimulation elicited an increase in regional blood flow (14C-iodoantipyrine technique) by 72%, and 39% on average in the frontal and occipital cortices, respectively, and 25% in the caudate-putamen (p less than 0.05; n = 12 in control, and 9 in the stimulation studies). It was found that observed results included little detectable contribution from current spread of the stimulus toward the adjacent structures (dorsal medullary reticular formation and cuneate fasciculus) surrounding the SOL and from retrograde activation of the cerebellar fastigial nucleus. Overall, the present study suggests that a certain vasomotor mechanism, which is activated upon excitation of the intermediate portion of the SOL, regulates the blood vessels of the brain as a vasodilator. PMID- 4021225 TI - "Calcium entry blockers" as cerebral protecting agents: comparative activity in tests of hypoxia and hyperexcitability. AB - The group of drugs described as "Ca2+-entry blockers" is chemically and pharmacologically heterogeneous. It is believed now that these drugs are useful in the treatment of ischemic disease. In an effort to define which drugs could offer the best therapeutic alternative, a comparative pharmacological study was made. Nine drugs (D-600, diltiazem, flunarizine, nicardipine, nifedipine, nimodipine, nitrendipine, verapamil, tiapamil) were tested in experimental screening models of brain hypoxia, ischemia, cellular intoxication and against bicuculline-induced seizures. Three types of activity were found. Verapamil, D 600, tiapamil and diltiazem were almost inactive, possibly due to their poor brain penetration. The dihydropyridines had a broad spectrum of activity, but considerable differences between these compounds exist. They all were active against hypoxia and less active against ischemia. Out of this subgroup, only nicardipine protected against metabolic intoxication and nifedipine and nicardipine could block seizure components at very high doses. Flunarizine was the only compound with a dose-related effect in all the tests. These results suggested that this combination of screening tests could be used to find compounds with an interesting activity in the field of cerebral protection. PMID- 4021226 TI - Cardiovascular effects of an ionophorous antibiotic, lonomycin A, in anesthetized dogs. AB - An intracoronary administration of ionomycin A, a K-selective ionophore, produced coronary vasodilation in the presence of pindolol in anesthetized dogs. Coronary vasodilation induced by ionomycin A, KCI and nifedipine was inhibited by pretreatment with an intracoronary injection of ouabain. This result suggests that lonomycin A-induced coronary vasodilation may be partly due to a stimulation of Na+, K+-ATPase as well as KCI and/or a decrease in Ca2+ influx as well as nifedipine. PMID- 4021227 TI - Modification of antinociceptive action of morphine by dopamine agonist and antagonist in mice. AB - A marked potentiation of the antinociceptive action of morphine was produced by haloperidol, but apomorphine had no effect on the antinociceptive action of morphine in acute experiments. Following chronic treatment with haloperidol, the antinociceptive action of morphine was significantly suppressed by apomorphine, and apomorphine shifted the dose-response curve of morphine to the right and increased the ED50 value of morphine by 2.3-fold. These results suggest that the suppressive action of apomorphine on the antinociceptive effect of morphine in chronic haloperidol-treated mice may be due to an increased sensitivity of post synaptic dopaminergic receptors to apomorphine. PMID- 4021228 TI - Dopaminergic modulation of the renal effect of arginine-vasopressin in water loaded rats. AB - In order to confirm whether dopamine inhibits the antidiuretic action of vasopressin in mammalian kidney, we examined interactions among arginine vasopressin (AVP), dopamine and haloperidol in water-loaded ethanol anesthetized rats. The submaximal dose of AVP causing antidiuresis was 80 microU in this preparation. Dopamine at the doses of 0.11, 1.1 and 11 micrograms/100 g body weight (i.v.) inhibited the antidiuretic effect of 80 microU AVP by 18 +/- 7, 27 +/- 6 and 36 +/- 14%, respectively. The effect of 1.1 micrograms/100 g body weight dopamine in inhibiting the action of AVP was completely reversed by haloperidol at 2.3 micrograms/100 g body weight. Single administration of dopamine or haloperidol was without effect on urine flow. These observations support the view that dopamine inhibits the antidiuretic action of vasopressin by dopaminergic receptors also in the mammalian kidney. PMID- 4021229 TI - Suppression of acetaldehyde accumulation by 4-methylpyrazole in alcohol hypersensitive Japanese. AB - Alcohol-sensitive Japanese subjects with facial flushing and an increase in heart rate during ethanol intoxication exhibited marked individual variation in accumulation of acetaldehyde. This variation correlated well with the intensity of the above mentioned physiological responses. Oral pretreatment with 10 mg/kg 4 methylpyrazole, which inhibited the ethanol elimination rate by 15-25%, strongly suppressed both acetaldehyde accumulation and the associated responses. Under this condition, the sensitivity to acetaldehyde appeared to be reduced, and the correlation between the acetaldehyde level and the physiological responses disappeared. The effectiveness of even a low dose of 4-methylpyrazole suggests its clinical usefulness for alleviation of acute acetaldehyde toxicity in alcohol hypersensitive Japanese individuals as well as in disulfiram-treated alcoholics. PMID- 4021230 TI - Antiarrhythmic effects of coronary vasodilators on canine ventricular arrhythmia models. AB - Antiarrhythmic effects of intravenous coronary vasodilators (verapamil, diltiazem, bepridil, trimetazidine and nicorandil) were evaluated using two canine ventricular arrhythmia models (halothane-adrenaline arrhythmia and digitalis arrhythmia), and the minimum effective plasma concentrations of the drugs were determined for each arrhythmia model. Verapamil (0.1 mg/kg), diltiazem (0.1 mg/kg), bepridil (1 mg/kg) and high dose trimetazidine (10 mg/kg) were effective on halothane-adrenaline arrhythmia; and the minimum effective plasma concentrations of the above drugs were less than 30 +/- 10 ng/ml, less than 18 +/ 5 ng/ml, 0.38 +/- 0.11 microgram/ml and 7.0 +/- 1.5 micrograms/ml, respectively. Nicorandil (1 mg/kg) did not suppress halothane-adrenaline arrhythmia. Verapamil, diltiazem and bepridil must have suppressed the halothane-adrenaline arrhythmia by blocking the Ca channel. Verapamil (1 mg/kg), diltiazem (1 mg/kg), bepridil (5 mg/kg), trimetazidine (3 mg/kg) and nicorandil (3 mg/kg) were ineffective on digitalis arrhythmia, even though their maximum hypotensive doses were used. PMID- 4021231 TI - Muscarinic acetylcholine receptors in the rabbit ciliary body smooth muscle: spare receptors and threshold phenomenon. AB - Interactions of several muscarinic drugs with their receptors were studied in the ciliary body smooth muscles of the rabbit. The ciliary body smooth muscles responded to carbachol, a muscarinic full agonist, with concentration-dependent contractions, and the pD2 value of carbachol was 5.16 +/- 0.05. Atropine, a competitive antagonist of muscarinic receptors, produced a parallel shift to the right in the concentration-response curves for carbachol. Pilocarpine which is a well-known partial agonist on muscarinic receptors in most smooth muscles did not cause any contraction in this tissue. The drug, however, behaved as a competitive antagonist on the muscarinic receptors in the ciliary body smooth muscles. The pA2 values of atropine and pilocarpine versus carbachol obtained from the Schild plot are 8.97 +/- 0.25 and 5.17 +/- 0.09, respectively. On the other hand, arecoline and oxotremorine acted as a partial agonist in this tissue. The intrinsic activity, and pD2 and pA2 values were 0.41 +/- 0.02, 4.93 +/- 0.05 and 5.32 +/- 0.05 for arecoline respectively, and were 0.26 +/- 0.02, 5.64 +/- 0.08 and 6.12 +/- 0.16 for oxotremorine, respectively. The pA2 values of these drugs were significantly larger than the corresponding pD2 values of the drugs. The values of the negative log molar dissociation constant of carbachol, arecoline and oxotremorine estimated by the method of partial irreversible blockade of spare receptors with 3 X 10(-6) M phenoxybenzamine were 4.53 +/- 0.08, 5.20 +/- 0.09 and 6.02 +/- 0.06, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4021232 TI - [Regional dysfunction in pneumonia]. PMID- 4021233 TI - [Local immune reactions to microorganisms]. PMID- 4021234 TI - [Methods of obtaining specimens for bacteriologic studies of respiratory infections]. PMID- 4021235 TI - [New problems in pulmonary bacterial infectious disease. 2. Diagnostic techniques. ii. Determination methods of causative organisms]. PMID- 4021236 TI - [Treatment: recent progress in antimicrobial chemotherapy]. PMID- 4021237 TI - [Respiratory care of acute respiratory failure due to respiratory infection]. PMID- 4021238 TI - [New problems in pulmonary infections. Limitations in surgical and medical treatment]. PMID- 4021239 TI - [Defining the position of steroid aerosol in the treatment of bronchial asthma- studies of steroid withdrawal methods with beclomethasone dipropionate inhaler]. PMID- 4021240 TI - [Latent asthma and so-called allergic bronchitis in patients with persistent cough]. PMID- 4021241 TI - [Bronchial involvement in sarcoidosis, retinalization of vessels in bronchial mucosa]. PMID- 4021242 TI - [A case of sarcoidosis involving multiple organs presenting hypothalamus hypophysis system disturbance]. PMID- 4021243 TI - [A case of SIADH without ectopic production of ADH from neoplasm, associated with superior vena cava syndrome caused by metastatic mediastinal tumor of pancreatic cancer]. PMID- 4021244 TI - [A case of amyloidosis with BHL (bilateral hilar lymphadenopathy), suspected to be sarcoidosis]. PMID- 4021245 TI - [Resection of lung cancer involving the mediastinal structures]. PMID- 4021246 TI - [Tracheal and tracheobronchial resection of bronchogenic carcinoma]. PMID- 4021247 TI - [Surgical problems in lung cancer with chest wall involvement]. PMID- 4021248 TI - [Role of computed tomography in assessing resectability of primary lung cancer]. PMID- 4021250 TI - [CT in the diagnosis of thoracic wall invasion of lung cancer]. PMID- 4021249 TI - [Diagnosis of tracheal and major bronchial carcinoma and the limitation of surgical therapy]. PMID- 4021251 TI - [Thromboexclusion technic for ruptured pseudoaneurysm of the descending thoracic aorta following extrapleural plombage thoracoplasty]. PMID- 4021252 TI - [Bronchoplasty for infant. Intrabronchial catheter pericutaneously placed to prevent obstructive atelectasis]. PMID- 4021253 TI - [A case of the left traumatic subclavian-internal jugular arteriovenous fistula]. PMID- 4021254 TI - [A case of coronary-pulmonary arterial fistula involving bilateral coronary arteries]. PMID- 4021255 TI - [A case of coronary artery-pulmonary artery fistula with a giant saccular aneurysm]. PMID- 4021256 TI - [Experience of median sternotomy for the surgical treatment of synchronous bilateral pneumothorax]. PMID- 4021257 TI - [The 60th Congress of the Japanese Society for Tuberculosis, Nagoya, April 7 and 8, 1985. Abstracts]. PMID- 4021259 TI - [Immunology and genetics of tuberculosis]. PMID- 4021258 TI - [Epidemiologic study of pulmonary tuberculosis and lung cancer]. PMID- 4021260 TI - [Physiopathology of epithelioid cell granuloma of the lung]. PMID- 4021261 TI - [Immunological indices in acute myocardial infarct depending on the period of the disease and the presence of circulatory failure]. PMID- 4021262 TI - [Uric acid metabolism in the acute period of myocardial infarct]. PMID- 4021263 TI - [Regulating role of phospholipids in the positive effect of isoptin in myocardial ischemia]. PMID- 4021264 TI - [Possible mechanisms of the occurrence of the early ventricular repolarization syndrome]. PMID- 4021265 TI - [Echocardiographic parameters of of the Soviet MKCh-25 valve]. PMID- 4021266 TI - [Case of congenital coronary artery aneurysms]. PMID- 4021267 TI - [Combined use of nitrates and beta-adrenergic blockaders in patients with acute myocardial infarct]. AB - A combination of isosorbide dinitrate (40-120 mg daily) and propranolol (80-160 mg) was administered to 146 patients during the early hours of myocardial infarction. The therapeutic effect was assessed for 10 days and compared to the effect observed in a control group of 70 patients selected at random. The combination used was shown to relieve the pain syndrome and extrasystolic arrhythmia during the early days of the disease. The occurrence of signs of heart failure was twice as low during the observation period, as compared to the control group. The treatment evoked typical hemodynamic changes: rhythm deceleration (by an average 7%), a fall in systemic arterial blood pressure (by 19%) and in "double product" (by 25%), a moderate reduction of cardiac output (by 15%) coupled with a marked drop in left-ventricular filling pressure (by 25%). The spread of infarcted area in the first days after the attack, as evidenced by serial electrocardiotopograms and the activity of serum CPK and its MB fraction, was recorded in 13.9% of the treated patients and in 44% of the controls (p less than 0.001). PMID- 4021268 TI - [Adaptation to physical loading in ischemic heart disease patients]. PMID- 4021269 TI - [Determination of the necrotic mass in inferior myocardial infarct by standard electrocardiography]. AB - A study of 28 patients with acute inferior myocardial infarction, who died 3 days after the attack, involved the comparison of necrosis weight data, as determined anatomically, with those obtained through the measurement of the R wave height and the Q wave (QS complex) depth, taken from standard leads and amplified remote leads from limbs. The comparison results suggest that intravital electrocardiographic determination of the necrosis weight is possible. A formula has been derived for the determination of the necrotized tissue weight (in grams) in patients with left-ventricular inferior infarction. PMID- 4021270 TI - [Diagnosis of dissecting aneurysms of the thoracic aorta]. AB - A study of the clinical pattern and findings of auxiliary investigation in 27 patients with dissecting aneurysms of the thoracic aorta showed that early diagnosis was necessary to improve the results of the treatment. A new non invasive diagnostic method, computerized tomography, was employed for the first time in domestic clinical practice. The diagnostic value of various instrumental investigation techniques was demonstrated with respect to research and clinical work. PMID- 4021271 TI - [Methodological approaches to assessing the effectiveness of anti-angina preparations in stenocardia patients using paired bicycle ergometry loads]. AB - Paired bicycle ergometry was used in 24 anginal patients to compare the efficiency of 10-20 mg isosorbide dinitrate, 20-30 mg corinfar and 40-80 mg propranolol. Isosorbide dinitrate showed maximum efficiency in half of the patients, corinfar in 1/4, propranolol in 1/6. Isosorbide dinitrate produced an effect with the very first dose more frequently, as compared to other drugs. Heart rate patterns at rest and under the action of corinfar and isosorbide dinitrate varied in different individuals and were related to the time of onset of an exercise-induced anginal attack. PMID- 4021273 TI - [Permeability of the erythrocyte membrane for sodium in hypertension and symptomatic hypertension]. AB - Sodium permeability of erythrocyte membranes was examined, using the recording of maximum rates of sodium-lithium countertransport, in patients with essential hypertension of stages II and III by the WHO classification, renal arterial hypertension, Itsenko-Cushing disease, pheochromocytoma, Conn's syndrome and in subjects with normal arterial pressure who made up a control group. Hypertensive patients demonstrated a more than 60% increase in erythrocyte membrane permeability, as compared to normotensive controls. In patients with pheochromocytoma, the permeability values were almost 40% as low as the control ones. No changes in sodium erythrocyte membrane permeability could be demonstrated in patients with renal hypertension, Itsenko-Cushing disease and Conn's syndrome. It is believed that the erythrocyte membrane permeability parameters can be used for the identification of essential hypertension in the differential diagnosis of hypertensions. PMID- 4021272 TI - [Effect of obzidan and pratsiol therapy on the blood plasma lipid profile and on the high- and low-density lipoprotein apoproteins in hypertension patients]. AB - The effect of an 8-week monotherapy with propranolol and pratsiol on plasma lipid levels and apo-Al and apo-B, apoproteins of high- and low-density lipoproteins (HDLP, LDLP) was studied in 20 patients with second-stage essential hypertension. Propranolol caused no significant changes in plasma lipid spectrum, however it produced a significant rise in apo-Al levels and reduced the cholesterol load index per weight unit of apo-Al in HDLP particles. Pratsiol treatment caused a significant reduction in plasma triglycerides, cholesterol of very-low-density lipoproteins, the cholesterol atherogenic coefficient and the apo-B/apo-Al ratio, and raised the level of HDLP cholesterol. The findings suggest that plasma lipoprotein effects should be taken into account in the choice of hypotensive agents. PMID- 4021274 TI - [Comparative evaluation of the dynamics of the echocardiographic parameters following open and closed mitral commissurotomy]. AB - A comparative study of early post-operative changes in a number of echocardiographic parameters was carried out in patients with pure and prevailing mitral stenosis following an open (24 patients) and closed (32 patients) mitral commissurotomy. The increment in the rate of early diastolic fall of the anterior mitral cusp, and total valve excursion, as well as reverse dynamics of the maximum left-atrial anteroposterior size were shown to differ significantly in post-open-commissurotomy patients from the corresponding parameters observed following the closed-technique operation. Mitral stenosis correction under visual control was associated with more effective as well as more radical results. PMID- 4021275 TI - [Reproducibility of several of the parameters of unidimensional echocardiography, sectoral scanning and tetrapolar rheoplethysmography of the chest cavity]. AB - The reproducibility of a number of echocardiographic and tetrapolar rheoplethysmographic parameters was checked at a one-hour interval in 26 coronary patients, and at a one-day interval in 54 patients. Left-ventricular diastolic diameter and stroke volume, as determined by the method of Rasmussen et al., and mean rates of closure of the anterior cusp of the mitral valve and myocardial fibre circular shortening showed the best reproducibility. Some parameters measured using the said technique showed a natural, but insignificant change over the study period, the respiration slightly affecting the diastolic diameter of the left ventricle. PMID- 4021276 TI - [Echocardiogram of young athletes on an annual training cycle]. PMID- 4021277 TI - [Dynamics of the phonocardiographic picture following the bioprosthesis of the mitral valve]. AB - Patterns of phonocardiographic changes were studied in 67 patients (aged 20 to 51 years) with acquired mitral disease 2 months to 6 years after the implantation of aortic xenobioprostheses, preserved in glutaraldehyde and mounted on a hard or flexible support. Phonocardiographic findings were compared with intracardiac hemodynamic data. Three stages and three types of phonocardiographic pattern were identified in patients with normally functioning xenobiovalves. As the postoperative period grew longer, the patients showed progressively smaller amplitudes of tones I and II, a smaller, if any, systolic output murmur and diastolic murmur; some patients no longer exhibited the prosthetic opening tone. PCG parameters showed stability between 2 and 6 years of follow-up. PMID- 4021278 TI - [Central hemodynamics in chronic alcoholics]. AB - Central hemodynamics were assessed in 86 chronic alcoholic patients in relation to the stage of the disease and the kind of alcoholic dependence. The values of major hemodynamic parameters were shown to depend on both the stage of the disease, and clinical manifestations of abstinence. The abstinence syndrome developing after a 3-5-day abstinence is associated with a gradual transition from eukinetic- to hypokinetic-type circulation, as the disease progresses. Hemodynamic shifts following recovery from acute delirium tremens are not related to the stage of the disease, and tend to hypokinetic-type circulation. During remission, hemodynamic parameters approach those of normal subjects. PMID- 4021279 TI - [Occurrence of persistent atrial fibrillation in acquired heart defects]. AB - Functional relationship between hemodynamic overstrain and left-atrial distension was investigated in 209 patients with acquired heart diseases and developing persistent atrial fibrillation. The development of constant atrial fibrillation was shown to depend on the correlation between mean left-atrial pressure and size, and functional relations between the two parameters, i. e. their critical ratio at the time when constant fibrillation is established, were determined. The critical curves which define this relationship for males and females demonstrate that constant fibrillation develops in patients with high mean pressure in the left atrium that is only slightly distended, and in patients with lower mean pressure in a considerably distended left atrium. PMID- 4021280 TI - [Mechanism of the anti-arrhythmic action of phosphocreatine in acute myocardial ischemia]. AB - The association between phosphocreatine's antifibrillatory action and its effect on the excitement propagation processes in the ischemic area was investigated under acute coronary arterial occlusion in dogs. Ischemia considerably reduced the amplitude, and increased the duration and time of onset, in local electrograms, and provoked cardiac fibrillation at the time of occlusion or during the recovery of coronary flow. A single intravenous injection of 300 mg/kg phosphocreatine eliminated cardiac fibrillation and largely prevented electrographic changes in the ischemized area. Phosphocreatinine, phosphocreatine's structural analogue, produced a similar effect. It is suggested that antiarrhythmic action of phosphocreatine and phosphocreatinine is mediated by their membrane effects. PMID- 4021281 TI - [Ultrastructure of the heart muscle in experimental myocardial infarct following physical training]. AB - The ultrastructure of peri- and extra-infarction areas was examined in the left ventricular myocardium of rats after swimming exercise. The ultrastructural study of cardiomyocytes and blood capillaries has suggested that regular exercise under experimental myocardial infarction improves blood supply to the heart muscle, prevents fibrillogenesis and activates compensatory-adaptive response of the intracellular regeneration type within components of the capillary wall and cardiomyocytes. PMID- 4021283 TI - [Changes in the adrenergic mechanisms regulating cardiac activity and coronary circulation in experimental diabetes mellitus]. AB - The effect of hyperglycemia on adrenergic response of the heart and coronary vessels was examined, using an alloxan diabetes model, in an experimental study involving catheterization, extracorporal perfusion and coronary arterial resistance measurement in dogs with intact thoracic cavities. Experimental diabetes mellitus was shown to be associated with enhanced positively chronotropic--and weakened negatively chrono- and inotropic--cardiac response to catecholamines introduced into the perfusion flow. Adrenergic reactive dilatation of coronary vessels was first enhanced, and later weakened, as glycemia progressed. It is assumed that a disturbance of hormonal interrelations due to insulin deficiency may play a role in the mechanism of changed adrenergic response of the heart and coronary vessels in experimental diabetes mellitus. PMID- 4021282 TI - [Elimination of disorders of the elasticity and contractile function of nonischemic portions of the heart in myocardial infarct by using glucose and uridine]. AB - A study of an isolated auricle showed that one day after the infarction the extensibility of the atrial myocardium was reduced, the Starling curve was depressed to result in about a two-fold decrease of the peak systolic tension, and atrial myocardial resistance to hypoxia and excessive calcium was also decreased. This complex of shifts was considerably diminished or eliminated altogether by means of building up an excessive glucose concentration or the administration of uridine, a cofactor of glycogen resynthesis. Therefore, the data obtained suggest that uridine can be used for correcting contractile disturbances of nonischemic compartments of the heart in myocardial infarction. PMID- 4021284 TI - [New possibilities for improving cardiologic care]. PMID- 4021285 TI - [Lipid content of the blood plasma and thrombocyte aggregation in myocardial infarct patients]. PMID- 4021286 TI - [Effect of low-density lipoproteins on neutrophil chemotaxis in chronic ischemic heart disease patients]. PMID- 4021287 TI - [Patient hemodynamic indices in the course of the year following myocardial infarct]. PMID- 4021288 TI - [Effect of korinfar on the central and peripheral hemodynamics of hypertension patients]. PMID- 4021289 TI - [Inotropic effect of parathormone]. PMID- 4021290 TI - [Electrical stability of the heart and the arrhythmogenic effect of isoptin]. PMID- 4021291 TI - [Complex evaluation of the reactions of the cardiovascular system to emotional stress in young people]. PMID- 4021293 TI - [Myocardial regional contractile function of the right ventricle]. AB - On the basis of the angiocardiographic examination of 22 individuals without cardiovascular diseases or suffering from congenital heart disease with mild hemodynamic changes, the authors devised the method for assessing the regional contractile function of the right ventricle myocardium founded on the anatomical principle of the division of the right ventricle chamber into different portions. The possibility of the quantitative evaluation of the functional status of different portions of the right ventricle is demonstrated. PMID- 4021292 TI - [Clinico-hemodynamic correlations in patients with a postinfarct aneurysm of the left ventricle]. AB - Eighty-four patients with left-ventricular post-infarction aneurysm were examined, 74 of those showing clinical signs of circulatory insufficiency. Selective coronarography and left roentgenocinematoventriculography were performed in all cases. Volumetric parameters and the ejection fraction were estimated for the total and contractile segment of the left ventricle. Statistical treatment of the data thus obtained demonstrated a relationship between the segmental contractility and manifestation of clinical signs of circulatory insufficiency. The limits were established for increments in residual and end-diastolic volumes that lead to the development of clinical manifestations of circulatory insufficiency. An increased end-diastolic pressure seems to be indicative of reduced elasticity (pliancy) of the left-ventricular myocardium, as reflected in markedly disturbed segmental contractility of the left-ventricular wall. PMID- 4021294 TI - [Use of a psychoemotional stress test in ischemic heart disease, hypertension and heart rhythm disorders]. AB - Forty male patients with coronary heart disease and essential hypertension, as well as 10 normal subjects, were examined, using a psychoemotional test with simultaneous monitoring of arterial blood pressure (BP), heart rate and ECG patterns. The test revealed disorders of cardiac rhythm in 28.6% of coronary patients and induced signs of myocardial ischemia and an anginal attack in 2. Signs of myocardial ischemia were more often provoked in coronary patients by physical stress tests as compared to those involving psychoemotional stress. In hypertensive patients, psychoemotional stress was associated with a more pronounced arterial BP rise, as compared to the results in normotensive individuals (normal subjects and coronary patients). Psychoemotional stress tests can be used alongside other kinds of tests in patients with coronary disease, essential hypertension and cardiac rhythm disorders. PMID- 4021295 TI - [Diagnostic and practical significance of the frequency changes in the electrical impulses of implanted pacemakers]. AB - The data on 1050 patients with implanted electric pace-makers are summarized, and the diagnostic and practical value of changes in the frequency of pulses they generate is discussed. PMID- 4021297 TI - [Assessment of heart rhythm in patients with dilated cardiomyopathy based on daily ECG monitoring data]. AB - The quantitative and qualitative characteristics of arrhythmias were examined, using continuous 24-hour ECG monitoring, in 25 patients with dilatation cardiomyopathy. Supraventricular extrasystole was found in 100% of patients with the sinus rhythm, and ventricular extrasystoles, in 94% of patients, being most commonly associated with poor prognosis (polytopic extrasystoles in 84%, paired extrasystoles in 60%, and paroxysmal ventricular tachycardia in 40%). Disorders of atrio-ventricular conductivity were recorded in 47.6% of patients with the sinus rhythm, 23.8% of those showing a permanent 1st-degree block, and the rest, a transient block of the 1st--3d degree. It was demonstrated that arrhythmias could serve as a permanent sign of dilatation cardiomyopathy, being most commonly of a complex nature and associated with poor prognosis. PMID- 4021296 TI - [Use of verapamil for treating patients with unstable stenocardia]. AB - Verapamil in a 400 mg daily dose was used in 64 coronary patients with the unstable angina syndrome, their condition being assessed by means of coronarography (40) and the cold test (24). Anginal attacks subsided in more than 60% of the patients treated with verapamil alone or in combination with long acting nitrates, and their treatment was continued on an out-patient basis. In 24 patients, the drug had no effect and was discontinued. Typically, all the three major coronary arteries were affected in these patients, and they were refractory to other antianginal drugs. Myocardial infarction developed during hospital stay in 7 (11%) patients. The cold test has no predictive value with respect to the efficiency of verapamil in these patients, as the rate of positive tests is rather low. The drug taken in a 400 mg dose is easily tolerated by patients over long periods of treatment (up to 1.5 pears), however, their circulatory status should be closely monitored because of a risk of heart failure and arterial hypotension. PMID- 4021298 TI - [Comparison of the indices of left ventricular pumping function, contractility, myocardial metabolism and the magnitude of the R wave on the ECG of ischemic heart disease patients]. AB - Central hemodynamics, myocardial contractility and consumption of major energy substrates (lactate, glucose, non-esterified fatty acids, NEFA), as well as the total R wave amplitude from 12 standard leads were assessed in 20 patients with neurocirculatory dystonia (the control group) and 36 patients with chronic coronary disease. The changes in central hemodynamics and contractility were particularly marked in 12 of the more severe coronary cases with a raised total R wave amplitude. Myocardial energy supply in such patients is provided at the expense of NEFA. The mildest cases, whose total R wave amplitude was as low as that of the controls, showed unchanged left-ventricular contractility and normal hemodynamic response to the atrial stimulation test. Myocardial glucose and lactate extraction prevails in these patients. It is suggested that a relationship may exist between the pattern of myocardial energy metabolism and the amplitude of electrocardiographic R wave. PMID- 4021299 TI - [Importance of combined instrumental study methods in the expertise of the work capacity of ischemic heart disease patients with stable stenocardia]. AB - Working capacity of 87 coronary patients with stable angina was assessed on the basis of a functional classification of the results of non-invasive investigations (resting ECG, bicycle ergometry, echocardiography). Bicycle ergometry proved to be the most informative method providing indirect evidence of coronary reserve. An objective assessment of the condition of coronary patients can be made using values of exercise tolerance (threshold capacity and volume of work), heart rate and double product at the peak of exercise. A close correlation exists between the severity of atherosclerotic affection of coronary arteries and individual exercise tolerance, which can be used in the medical evaluation of the working capacity of coronary patients with stable angina pectoris. PMID- 4021300 TI - [Effect of intensive physical training on the hospital stage of the rehabilitation of patients with macrofocal myocardial infarct]. AB - Thirty-five patients with large-focal myocardial infarction were divided into the main (21) and the control (14) groups. The main-group patients were subjected to intensive exercise beginning with day 10-22 of the disease; its program was designed so as to match the data of bicycle ergometry checkups and included bicycle-ergometric riding and rationed walking. It was demonstrated that the main group patients showed better physical stress tolerance, improved myocardial functional potentials, better psychological outlook and smaller pulmonary venous congestion at the time of transfer to the sanatorium stage of rehabilitation. It is suggested that exercise be incorporated in the hospital rehabilitation complex for patients with large-focal myocardial infarction. PMID- 4021301 TI - [Multifactorial analysis of the hemodynamic reactions to a physical load in hypertension]. AB - Multifactorial analysis of findings from 66 essentially hypertensive patients and 14 normal subjects investigated during bicycle ergometry (250 and 500 kgm/min) demonstrated a relationship between hemodynamic changes and the patient's baseline status, age and stage of the disease. Hypertensive patients showed greater AP response to exercise and smaller changes in heart productivity and vascular tone, as compared to normal subjects with similar resting hemodynamic status. Patients with high resting AP and CI values showed smaller shifts during bicycle ergometry, as compared to other patients at the same stage of the disease, while diastolic AP increase was more pronounced in elderly patients. PMID- 4021302 TI - [Function of the heart chambers in acute myocardial infarct]. AB - A study of 87 patients, admitted to hospital within the first day of acute myocardial infarction (AMI) identified 3 groups of patients on the basis of their pulmonary capillary occlusion pressure (OP) values. Sixteen normal subjects made up the control group. Myocardial contractility and volume characteristics obtained by sectoral scanning were reviewed. It was demonstrated that the contractility of the left and right heart chambers had different patterns of change in relation to the magnitude of pressure: left-atrial and right ventricular ejection fraction (EF) gradually declined, and normal pressure values were associated with right-ventricular hyperfunction. Right-ventricular EF also decreased as the OP grew, yet it did not reach the critical values as observed with the left-ventricular EF. The predominance of the right-ventricular function over the left-ventricular one might be one of the mechanisms underlying the development of insufficiency in the lesser circulation. Contractility unbalance was also shown to exist between the right and left atria. A rise in the end systolic volume in the presence of unchanged end diastolic volume is the earliest manifestation of reduced left-ventricular contractility in acute myocardial infarction. PMID- 4021303 TI - [Lipids and apoproteins in the blood plasma of children with a hereditary disposition to ischemic heart disease]. AB - An investigation of children with aggravated heredity (coronary disease), and those with vegetovascular dystonia whose parents had no clinically apparent coronary disease demonstrated unidirectional shifts in the lipoprotein system of the two samples as compared to the controls: increased cholesterol levels in low density lipoproteins and lowered cholesterol in high-density lipoproteins and apoprotein A1. In children with aggravated heredity, these changes are also associated with vegetovascular dystonia, whereas in the absence of the latter they are not apparent or minimal. At the same time, certain differences in cholesterol distribution over lipoprotein fractions and protein/lipid ratios suggest that mechanisms of changes are not identical in children with aggravated heredity and those free from it. PMID- 4021304 TI - [Ventricular pre-excitation syndrome in adolescents]. AB - A total of 26 adolescents (aged 14-18) with the premature ventricular exitement (PVE) syndrome were under observation, 17 of them being followed up in the time course of 2 to 10 years. The LGL syndrome and Maheim type were rather often noted among such adolescents. Paroxysmal tachycardia attacks and in some cases extrasystole were recorded in 34% of the patients with the PVE syndrome. Bicycle ergometry evidenced a decrease in the functional capacity of the cardiovascular system of the adolescents with the PVE syndrome. PMID- 4021305 TI - [Action of noradrenaline and dopamine on the pacemaker cells of the normal rat sinus node and in pharmacological sympathectomy]. AB - The authors studied the action of the physiological concentrations of catecholamines on the major parameters of the action potentials of the true pacemakers, using a graphic analysis of their electric activity at the intracellular microelectrode lead. Desympathization was carried out with the help of daily intraperitoneal injections of guanethidine solution for six weeks. Noradrenaline and dopamine have a similar effect on the electrogenesis of the pacemakers by decreasing a relative threshold of auto-stimulation and decreasing the steepness of the potential growth in phase 4 on the curve of the action potential. Pharmacological desympathization leads to the development of hyper reactivity of the true pacemakers to noradrenaline and dopamine and triggers off changes in the regulation of the electric activity of these cells by catecholamines. PMID- 4021306 TI - [Cold-induced arrhythmias in the isolated rabbit atrium studied by mapping]. AB - Arrhythmias developing in isolated rabbit atria following the cooling of the perfusion solution were studied by multielectrode mapping. In 10 out of the 12 initially invulnerable preparations, the cooling to 27 +/- +/- 0.7'C induced arrhythmias. The effect was reversible, disappearing with the temperature normalization. Mapping showed that in 60% of the cases the arrhythmias were caused by the emergence of the leading cycles (functionally determined re-entry). In 40% of the cases, the re-entry was not demonstrable by mapping. However, arrhythmias in these experiments developed at the same temperature and had the same period as the leading cycles. The appearance of arrhythmias was closely correlated with a decrease in the wave length which strongly suggests the re entry mechanism of hypothermic arrhythmias. PMID- 4021307 TI - Pressure dependence of exaggerated natriuresis in two-kidney, one clip Goldblatt hypertensive rats. AB - This study evaluated the responses of each kidney of two-kidney, one clip Goldblatt hypertensive rats to acute volume loading to delineate the contribution of elevated perfusion pressure to the mechanisms of the exaggerated natriuresis in this model of hypertension. Eleven Goldblatt animals (0.2 mm clip 3 weeks prior to study) were studied at spontaneous blood pressure for each kidney's response to volume loading. In 11 other Goldblatt animals an aortic clamp between the renal arteries allowed reduction of perfusion pressure for the left, nonclipped kidney to normal levels. Ten normal rats served as controls. Renal function was examined during control periods and following the infusion of 3.5% body wt of 154 mM X liter-1 NaCl at 22.5 ml X hr-1. An exaggerated natriuresis was observed for the left, nonclipped kidney of the hypertensive Goldblatt rats, while the clipped kidney exhibited an attenuated natriuresis compared to either kidney of normal control rats. Reduction of perfusion pressure to the nonclipped kidney of Goldblatt animals to normal levels resulted in reduced clearance and excretory function before volume loading and attenuated its natriuretic response to levels less than those for the Goldblatt group at spontaneous, hypertensive blood pressure. The exaggerated natriuresis observed at hypertensive blood pressure was attributable to increases of filtered load of Na+ and reduced fractional absorption. These observations indicate that an exaggerated natriuresis occurs in the two-kidney, one clip Goldblatt hypertensive rat and that this phenomenon depends on the elevated renal perfusion pressure to the nonclipped kidney. PMID- 4021308 TI - Effect of protein intake on renal function and structure in partially nephrectomized rats. AB - To examine the effect of high protein intake on renal function and structure in rats with 5/6 nephrectomy chronic renal failure, we pairfed rats with chronic renal failure and sham-operated control rats diets of 14 or 37% protein content for up to 6 months. High protein intake accelerated mortality in rats with chronic renal failure and resulted in a more rapid rate of decrease in renal function as established by plotting the reciprocal of plasma creatinine versus time. High protein intake also increased urine protein excretion in experimental and control rats. High protein intake was associated with increased tubular dilatation and interstitial inflammation, both of which were striking features in rats with chronic renal failure. Glomerular sclerosis was prominent in rats with chronic renal failure. These rats had smaller glomerular tuft dimensions than control rats irrespective of their protein intake. We conclude that high protein intake accelerates the course of chronic renal failure in rats. The pathologic process involves glomerular sclerosis; however, interstitial inflammation and renal tubular changes leading to cyst formation also appear to influence the process adversely. PMID- 4021309 TI - Spontaneous glomerular IgA deposition in ddY mice: an animal model of IgA nephritis. AB - It was found that ddY mice derived from non-inbred dd-stock mice brought from Germany before 1920 and then raised in Japan developed spontaneously IgA dominant deposition in the glomerular mesangium. In this report we give a detailed natural history of the renal pathology of those mice. The animals were fed rodent laboratory chow and sacrificed in groups of 9 to 10 at 6, 10, 16, 24, 28, 40, and 59 weeks of age. The bladder urine was analyzed, serum immunoglobulins were measured, and the kidney specimens were evaluated with light, fluorescent, and electron microscopy. Proteinuria was (plus) to (2 plus) after 28 weeks and (2 plus) to (3 plus) at 59 weeks with negative hematuria. Mesangial cell proliferation began to appear at 16 weeks, then progressed to a definite proliferative glomerulonephritis. At 59 weeks an additional increase of the mesangial matrix occurred. By immunofluorescence, there were IgG of (2 plus), IgM (plus) to (2 plus), IgA (plus) and C3 (plus) in the glomeruli until 28 weeks. However, IgA started to be dominant at 40 weeks and the glomerular pattern was IgA (2 plus) to (3 plus), IgG (plus) to (2 plus), IgM (+/-) to (plus) and C3 (plus) to (2 plus) at 59 weeks. Polyclonal IgA and IgG2a among immunoglobulins steeply rose at 40 weeks, and at 59 weeks IgA increased by 850%, IgG2a by 280%, IgG1 by 170%, IgG2b by 90%, and IgM by 60%, as compared with their level at 6 weeks. There was no anti-nuclear antibody. Thus, ddY mice, at least after the age of 40 weeks, can be used as a new animal model for spontaneous IgA nephritis. The probable origin of IgA is also discussed. PMID- 4021310 TI - Comparative effects of acetate and bicarbonate hemodialysis on left ventricular function. AB - To assess the comparative effects of hemodialysis with acetate versus bicarbonate base on left ventricular systolic function, we performed M-mode echocardiography on 36 patients prior to and immediately following 4-hr maintenance hemodialysis. Patients were initially dialyzed against either sodium acetate or sodium bicarbonate and 1 week later were dialyzed against the alternate base. The mean velocity of circumferential fiber shortening (mean Vcf, circumferences/s) was used to assess left ventricular systolic function. In patients with normal pre dialysis mean Vcf hemodialysis with acetate produced no significant change in mean Vcf, whereas hemodialysis with bicarbonate produced a significant increase in mean Vcf. In patients with low pre-dialysis mean Vcf hemodialysis with either base produced a significant increase in mean Vcf. Mean Vcf values obtained after hemodialysis with bicarbonate were significantly higher than those obtained after hemodialysis with acetate, both in patients with normal and low pre-hemodialysis mean Vcf. We conclude that hemodialysis with bicarbonate produces a comparatively greater improvement in left ventricular systolic function than hemodialysis with acetate. PMID- 4021311 TI - Calcium metabolism in uremic nephrocalcinosis: preventive effect of verapamil. AB - The aim of the present study was to examine calcium metabolism of the renal cortex in experimental chronic renal failure, together with morphologic criteria of nephrocalcinosis and to determine the effect of chronic verapamil administration on these parameters. In subtotally nephrectomized (SNX) rats 3 weeks after surgery, renal cortical calcium content increased more than two-fold. 45Ca incorporation into renal cortical slices in SNX revealed a 35% increase, associated with a 50% increase in a lanthanum-resistant fraction of 45Ca uptake. Radiocalcium wash-out curves in this group demonstrated abnormal retention of the isotope for up to 30 min of incubation. In contrast, radiocalcium incorporation and wash-out in SNX rats chronically treated with verapamil were similar to that obtained in the sham group. Verapamil administration significantly reduced, but did not normalize, renal cortical calcium content. Von Kossa staining demonstrated the deposition of calcium in the renal parenchyma of SNX rats. Ultrastructurally, it was accompanied by mitochondrial disorganization and calcification, as well as by the tubular basement membrane destruction and mineralization. These morphologic patterns of nephrocalcinosis were significantly ameliorated in SNX rats treated with verapamil. We conclude that chronic verapamil administration results in amelioration of uremic nephrocalcinosis. PMID- 4021312 TI - Increased bone aluminum deposition after subtotal parathyroidectomy in dialyzed patients. AB - Ten dialyzed patients underwent a systematic bone biopsy before and 19 +/- 9 months after subtotal parathyroidectomy (PTX). At the end of the follow-up period all the patients, except two, who complained of proximal myalgia, were asymptomatic. Compared to the bone biopsy specimen obtained prior surgery, decreased bone formation without mineralization impairment was observed after PTX. Despite an average decrease in aluminum gels intake after PTX, an increase in stained aluminum was observed (0.69 +/- 0.79 versus 1.20 +/- 0.95 mm/mm2, P less than 0.050). Aluminum accumulation depended on the pre-PTX bone aluminum load: pre- and post-PTX bone aluminum loads were correlated (r = 0.78, P less than 0.01). Bone aluminum accumulation was not related to the amount of aluminum gel intake after PTX; however, only two patients free of both bone aluminum deposit prior to PTX and aluminum gel intake after PTX had no stainable aluminum on the second bone biopsy after PTX. The only patient who had no decrease in bone formation after PTX had no increase in bone aluminum. Assuming that the patients had no aluminum deposit prior to dialysis, we measured the rate of bone aluminum accumulation. It rose from 0.11 +/- 0.09 mm/mm2/year prior to PTX to 0.40 +/- 0.25 mm/mm2/year after PTX (P less than 0.05) in the six patients who were maintained on phosphate binders and who had a decrease in bone formation after PTX. These six patients had unchanged aluminum gel intake.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4021313 TI - Mechanism of impaired urinary concentration in chronic primary glomerulonephritis. AB - To define the role of medullary damage and the influence of solute load and blood pressure (BP) in impairing urinary concentration, patients with chronic glomerulonephritis were investigated by histological and functional studies. In 59 biopsy specimens, the degree of medullary fibrosis was correlated inversely with urinary specific gravity and was significantly greater in hypertensive than in normotensive subjects. The following clearance studies were carried out in patients with a GFR of 15 to 40 ml/min in maximal antidiuresis: (1) Eight patients were studied while receiving a high sodium and protein diet and then after 1 week of low sodium, low protein diet; (2) ten patients were loaded with hypertonic saline (3%) to increase urine volume up to 25 to 30% of GFR; (3) the concentrating ability was compared in 15 normotensives and 15 hypertensives with comparable GFR; (4) the concentrating ability was studied in nine hypertensive patients before and after drug-induced normalization of BP. In (1) no change occurred in maximal urine osmolality (UOsm) even if fractional sodium excretion and filtered load of urea were reduced. In (2), values of UOsm fell below those of plasma osmolality. In (3), UOsm and negative free-water generation were lower in hypertensive than in normotensive subjects. In (4), normalization of BP was not associated with any change in UOsm. These results indicate that osmotic diuresis does not play a critical role in reducing urinary concentration. This defect is better accounted for by an intrinsic medullary damage, enhanced in hypertensive patients, which may impair the permeability of collecting ducts to water. PMID- 4021314 TI - Role of fibrinogen in the glomerular permeability of the perfused, isolated dog kidney. PMID- 4021315 TI - Phenomenological analysis of renal regulation of sodium and potassium balance. PMID- 4021316 TI - Metabolic control of renal vascular resistance and glomerulotubular balance. AB - Renal vascular resistance (RVR) and glomerulotubular balance were examined in isolated rat kidneys perfused at 100 mm Hg with 10 mM lactate (L) or 10 mM pyruvate (P) or 5 mM glucose (G) either alone or with a mixture of 20 amino acids (13.5 mM, AA); albumin oncotic pressure 24 +/- 1 mm Hg. RVR was L greater than P greater than G = AA. Vasodilation by G and AA was additive. Proximal tubular sodium-cotransport was evaluated from fractional reabsorption (FR) of phosphate (Pi), G, and L. FR Pi was 91% in AA, 86% in P, 72% in L, and 67% in G. Combining AA or P with L or G increased FR Pi to 89 to 90%. FRs of G and L by G and L perfused kidneys were 83 and 78%, respectively, and were increased to 97 to 99% by combining G or L with AA or P. P and AA also increased FR sodium and FR water when combined with L or G or when combined with each other. GFR correlated positively with FR sodium and FR water. AA combined synergistically with L to increase gluconeogenesis. These results indicate that, compared with pyruvate or AA, neither glucose nor lactate alone is a good energy source for proximal tubular reabsorption, that synergistic interactions between AA or pyruvate and lactate or glucose augment GFR by increasing proximal tubular reabsorption, and that the vasodilating effects of glucose and AA are not related directly to their effects on GFR. PMID- 4021317 TI - Effects of intra-animal nephron heterogeneity on studies of glomerular dynamics. AB - Quintuplicate determinations of the parameters measured in studies of glomerular dynamics revealed that the intra-animal coefficients of variation for Bowman's space and star vessel pressures, nephron filtration rate, and filtration fractions were 54 to 72% larger than the corresponding interanimal coefficients of variation; those for glomerular capillary pressure were more nearly equal. With a net efferent filtration pressure (delta PE) of 10.6 +/- SEM 1.9 mm Hg, the rats were far from filtration pressure equilibrium and the calculated ultrafiltration coefficient (Kf) of 2.1 +/- SEM 0.2 nl/min X mm Hg was lower than in many other studies. Statistical analysis revealed that the precision of estimates of both the measured and the derived parameters in glomerular dynamic studies is affected appreciably by ignoring the intra-animal effect. The importance of the intra-animal variance in glomerular dynamic studies is greatest when only one or two samples of each measured parameter are obtained in every rat (k = 1 or 2) and least when k is large. Triplicate sampling provides combined SEMs that are not greatly larger than those obtained with k = 5, however, and offers the greatest economy in studies of glomerular dynamics. The number of animals required to provide values with delta PE and Kf that are within +/- 20% of the "true" values is rather large. PMID- 4021319 TI - Effect of imidazole and indomethacin on hemodynamics of the obstructed canine kidney. AB - In the anesthetized dog renal blood flow (RBF) and its intrarenal distribution were investigated by the radioactive microsphere technique 24 hr after bilateral (BUL) and unilateral (UUL) ureteral ligation. In the control series indomethacin (IM) led to a decrease in RBF with outward shifting of zonal perfusions; imidazole (IA) did not cause significant changes in renal hemodynamics. In the BUL series there was a sharp drop in RBF with a proportional decrease in outer (OC) and inner (IC) cortical perfusion; IM treatment resulted in a further decrease in overall and zonal perfusions. IA, a selective inhibitor of thromboxane synthetase, relieved IC vasoconstriction. In the ligated kidney of the UUL preparations decrease in RBF was due to OC vasoconstriction, while IC perfusion equalled controls. IM led to an overall vasoconstriction in all cortical layers; IA did not influence either total RBF or its distribution. It was concluded that BUL "unmasked" TXA2 production in the IC layers, while IM treatment, by inhibiting the production of PGE2, PGI2, and TXA2, resulted in an overall vasoconstriction both in controls and the BUL and UUL preparations. PMID- 4021318 TI - Phosphate transport by brushborder membranes from superficial and juxtamedullary cortex. AB - In vivo studies indicate that the extent of phosphate (Pi) reabsorption differs in proximal tubules of superficial (SC) and juxtamedullary (JM) nephrons. Since Na-gradient (Nao greater than Nai) dependent uptake of Pi by the luminal brushborder membrane (BBM) may be the rate-determining step in proximal tubular reabsorption, we studied this transport system in brushborder membrane vesicles (BBMV) prepared from SC and JM renal cortex of dogs fed either a low phosphorus diet (LPD, 0.07% Pi) or high phosphorus diet (HPD, 1.2% Pi). In the initial uphill phase (that is, "overshoot"), the rate of Na-gradient dependent uptake of Pi was significantly greater [delta + 35%] in BBMV from the SC cortex (BBMV-SC) than in BBMV from the JM cortex (BBMV-JM) of the dogs fed LPD. Higher Na dependent Pi uptake was due to significantly (P less than 0.05) higher apparent Vmax (mean +/- SEM, nmoles Pi/0.5 min/mg protein) for Pi in BBMV-SC (7.5 +/- 1.57) compared with Vmax in BBMV-JM (6.05 +/- 1.74). Higher transport of Pi in BBMV-SC compared with BBMV-JM of dogs fed LPD was a difference relatively specific for the Na-dependent Pi uptake system; Na+ independent uptake of Pi and Na-dependent uptake of D-glucose were lower in BBMV-SC than in BBMV-JM. The size of BBMV or rate of Na+ uptake did not differ between BBMV-SC and BBMV-JM. The Na gradient dependent uptake of Pi was no different between BBMV-SC and BBMV-JM from dogs stabilized on HPD.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4021320 TI - Effect of acute potassium load on reabsorption in Henle's loop in chronic renal failure in the rat. AB - To determine the effect of an acute load of potassium on potassium reabsorption by the loop of Henle in chronic renal failure, the right kidney was removed and branches of the left renal artery were ligated in 17 rats. One week later and after 2 days of a potassium-free diet, rats were studied before (period 1) and after (period 2) acute loads of potassium chloride (KCl group), equimolar sodium chloride (NaCl group) or no solute (time control). The KCl load increased urinary potassium excretion to a greater extent (from 5 to 50%, P less than 0.005) than in NaCl (14 to 27%) or time control (9 to 14%), and caused as great a diuresis and natriuresis as did NaCl. Fractional delivery of water, sodium, and potassium to the end-proximal tubule increased similarly in the NaCl and KCl groups and slightly less so in the time control group in period 2. The major finding was a striking increase in potassium delivery to the beginning of the distal tubule (from 17 to 37%) in period 2 which was substantially greater than in the combined control groups (13 to 19%, P less than 0.025) and was equivalent to three quarters of urinary potassium excretion. This was the consequence of an increase in the filtered load of potassium, an increase in absolute delivery of potassium from the proximal tubule (P less than 0.005), and a decrease in fractional potassium reabsorption by the loop of Henle from 64 to 48%, versus 72 to 69% in the control groups (P less than 0.01). These results suggest that the proximal tubule and, in particular, Henle's loop play a role in excreting an acute potassium load in chronic renal failure. PMID- 4021322 TI - Enhanced reabsorption of bicarbonate and phosphorus by the addition of amino acids in the isolated perfused rat kidney. PMID- 4021323 TI - [Malabsorption syndrome--review of definition, pathogenesis and diagnosis. 2]. PMID- 4021321 TI - Course of acute renal failure studied by a model of creatinine kinetics. AB - A computerized model of creatinine kinetics was developed to predict the relationship between creatinine clearance [G(t)] and plasma creatinine concentration [C(t)] in patients with postischemic acute renal failure (ARF). A comparison of predicted to measured values in 35 episodes of ARF in 27 patients revealed three patterns of declining G(t) following an ischemic insult. Pattern A, characterized by an abrupt step decrement in G(t) following an isolated renal ischemic episode lasting minutes or hours, was observed in nine patients. It was followed invariably by an immediate ramp increment in G(t), despite which C(t) continued to increase for several days. Urinary indices during the period of increasing azotemia were consistent with the resolving stage of ARF. Patterns B (N = 15) and C (N = 11) were associated with persistent renal ischemia of long (days to weeks) duration and were respectively characterized by prolonged ramp or exponential decrements in G(t). A concurrent increase in C(t) was associated with urinary indices typical of the maintenance or sustained stage of ARF. Recovery of G(t) was observed in only two-thirds of patterns B and C cases and took the form of a ramp or exponential increment. Because G(t) and total body water were changing rapidly in ARF, changes in measured plasma creatinine levels alone failed to identify these patterns of deteriorating or improving renal function. However, when the computerized model was used in conjunction with daily measured values of C(t) and body weight and occasional estimates of G(t), the course and prognosis of ARF in individual patients were illuminated. PMID- 4021324 TI - [Calculation of the effect of phototherapy with reference to different radiation variants. II. Prognostic evaluation of the effect of phototherapy by intermittent and continuous phototherapy]. PMID- 4021325 TI - [Coincidence of kidney damage and diagnostic parameters in neurogenic bladder emptying disorder. An analysis of 76 cases with myelodysplasia]. PMID- 4021326 TI - [Effect of room climate on acute respiratory diseases in day care centers]. PMID- 4021327 TI - [Diagnosis and surgical treatment of nonepithelial stomach tumors]. PMID- 4021329 TI - [Possibilities for emergency intraoperative cytological diagnosis in cancer patients]. PMID- 4021328 TI - [Perforation of cancerous stomach tumors]. PMID- 4021330 TI - [Effect of surgical and combined treatment on the sympathetic-adrenal function of patients with cancer of the esophagus and proximal portion of the stomach]. PMID- 4021331 TI - [Hemodynamics and blood oxygen transport following operations on patients with chronic nonspecific suppurative lung diseases]. PMID- 4021332 TI - [Principles of immunotherapy in osteomyelitis with respect to the recommendations of the World Health Organization]. PMID- 4021334 TI - [Substantiation of the prospective need for hospital cancer care based on the prognosis of malignant neoplasm morbidity]. PMID- 4021333 TI - [Extracorporeal percutaneous transhepatic cholangiocholecystic shunting as a treatment method for patients with obstructive jaundice due to cancer of the hepatic portal]. PMID- 4021335 TI - [Organization of anesthesiological support in outpatient care]. PMID- 4021336 TI - [Giant esophageal polyp]. PMID- 4021337 TI - [Leiomyoma of the stomach]. PMID- 4021338 TI - [Benign stomach tumors]. PMID- 4021339 TI - [Hemangioma of the small intestine simulating iron-deficiency anemia]. PMID- 4021340 TI - [Development of tumors in the area of rectal fistulae]. PMID- 4021341 TI - [Resection of the left hepatic lobe for hemangioma]. PMID- 4021342 TI - [Retroperitoneal cysts]. PMID- 4021343 TI - [Retroperitoneal mesenchymoma]. PMID- 4021344 TI - [Metachronous bilateral cystic lymphangioma of the retroperitoneal space in a pregnant woman]. PMID- 4021345 TI - [2 cases of lung teratomas]. PMID- 4021347 TI - [Recurrence of Madelung's syndrome]. PMID- 4021346 TI - [Metastases of breast cancer in the late period after radical treatment]. PMID- 4021348 TI - [Acute torsion of the stomach]. PMID- 4021349 TI - [Torsion of the greater omentum]. PMID- 4021350 TI - [Diaphragmatic injuries in multiple trauma]. PMID- 4021351 TI - [Subphrenic abscess]. PMID- 4021352 TI - [False acute abdomen due to Waterhouse-Friderichsen syndrome]. PMID- 4021353 TI - [Leukocytic index of intoxication in acute surgical diseases of the abdominal organs]. PMID- 4021354 TI - [Shotgun pellet wounds of the abdominal organs]. PMID- 4021355 TI - [Gallbladder and bile duct injuries in abdominal trauma]. PMID- 4021356 TI - [Multiple injuries to the right branch of the portal vein, gallbladder, duodenum and pancreas]. PMID- 4021357 TI - [Liquid-crystal thermography in the diagnosis of acute postoperative pancreatitis]. PMID- 4021358 TI - [Causes of the development and clinical forms of acute biliary pancreatitis]. PMID- 4021359 TI - [Multiple wounds of the abdominal organs via the perineum]. PMID- 4021360 TI - [Complex approach to the detection of insufficiency of esophagogastric junction in children]. PMID- 4021361 TI - [Rheorectography in children with megacolon]. PMID- 4021362 TI - [Prolonged drip lavage of the caliceal-pelvic system of the kidneys after operations in the complex treatment of calculous pyelonephritis in children]. PMID- 4021363 TI - [Effect of surgical treatment of chronic hematogenic osteomyelitis in children on the state of humoral and cellular immunity]. PMID- 4021364 TI - [Effect of irradiation with a helium-neon laser on the functional state of peripheral blood circulation during treatment of children with long-standing non healing wounds]. PMID- 4021365 TI - [Acute destructive pneumonia in children]. PMID- 4021366 TI - [Characteristics of the surgical treatment of funnel chest associated with curvature of the spine in children]. PMID- 4021367 TI - [Regional blood flow in fractures of femoral diaphysis in children]. PMID- 4021368 TI - [Endovascular occlusion of internal seminal veins in varicoceles in children and adolescents]. PMID- 4021369 TI - [Surgical treatment of atresia of the rectum with vaginal fistula in girls]. PMID- 4021370 TI - [Treatment of complicated stomach and duodenal ulcers in children]. PMID- 4021371 TI - [Perforation of peptic ulcer of Meckel's diverticulum in children]. PMID- 4021372 TI - [Diagnosis of early postoperative complications in pediatric abdominal surgery]. PMID- 4021373 TI - [Experience with the treatment of a septicopyemic form of acute hematogenic osteomyelitis in children using intra-arterial infusions of antibiotics]. PMID- 4021374 TI - [Urologic diseases in children manifested by symptoms of acute abdomen]. PMID- 4021375 TI - [Possibilities of emergency excretory urography in the differential diagnosis of acute surgical and urologic diseases in children]. PMID- 4021376 TI - [Experience using intravenous anesthesia in pediatric anesthesiology]. PMID- 4021377 TI - [Treatment of suppurative-septic diseases complicated by dysbacteriosis in young children]. PMID- 4021378 TI - [Rehabilitation of patients after Duhamel's operation in Hirschsprung disease]. PMID- 4021379 TI - [Destructive cholecystitis in children]. PMID- 4021380 TI - [Abdominal syndrome in erysipelas complicated by myocarditis]. PMID- 4021381 TI - [Developmental anomalies of the rectum with fistulas of the genital organs in girls]. PMID- 4021383 TI - [Parkes Weber syndrome in a child]. PMID- 4021382 TI - [Treatment of varicocele in children]. PMID- 4021384 TI - [2 cases of successful treatment of children with extremely critical burns]. PMID- 4021385 TI - [Tactics in the treatment of external intestinal fistulas in children]. PMID- 4021386 TI - [Current state of surgery of the esophagus]. PMID- 4021387 TI - [Lymphosorption in the complex treatment of destructive pancreatitis]. PMID- 4021388 TI - [Staphylococcal bacteremia in patients with phlegmonous cholecystitis]. PMID- 4021389 TI - [Anaerobic clostridial infection of surgical wounds]. PMID- 4021390 TI - [Local treatment of post-injection abscesses with a combination of oxytocin and antibiotics]. PMID- 4021391 TI - [Late postoperative abscesses of the abdominal cavity]. PMID- 4021392 TI - [Erosive hemorrhages as a complication of suppurative mediastinitis]. PMID- 4021393 TI - [Phagocytosis in patients with a surgical profile uncomplicated and complicated by suppurative infection]. PMID- 4021394 TI - [Use of prostheses made of highly porous polytetrafluoroethylene in the reconstruction of veins]. PMID- 4021395 TI - [Preoperative prevention of surgical infections]. PMID- 4021396 TI - [Treatment of patients with extensive circular burns on beds with an air cushion]. PMID- 4021397 TI - [A variant of Desault's bandage]. PMID- 4021398 TI - [An improved method of incision of carbuncles]. PMID- 4021399 TI - [Surgical concept of infection]. PMID- 4021400 TI - [Epidemiology and unsolved problems of prevention of suppurative septic infections in surgery]. PMID- 4021401 TI - [Results of treatment of pleural empyema complicated by infection]. PMID- 4021402 TI - [Surgical tactics in thoraco-abdominal injuries]. PMID- 4021403 TI - [Low-frequency ultrasonics in primary surgical debridement of suppurative wounds of soft tissues]. PMID- 4021404 TI - [Value of bacteriological studies in the diagnosis, treatment and prevention of postoperative infection]. PMID- 4021405 TI - [Use of low-frequency ultrasonics in the complex treatment of acute suppurative diseases of the fingers and hand]. PMID- 4021406 TI - [Changes in the blood coagulation system in the stage of burn cachexia]. PMID- 4021407 TI - [Difficulties in the treatment of combined burns of the esophagus and stomach]. PMID- 4021409 TI - [Progressive necrosis of the skin]. PMID- 4021408 TI - [Surgical treatment of acute ulcers of the gastrointestinal tract in burns]. PMID- 4021410 TI - [Treatment of open fractures of long tubular bones]. PMID- 4021411 TI - [Gnotobiological principles of the prevention and treatment of mechanical injuries of the limbs]. PMID- 4021412 TI - [Effect of arterial and venous insufficiency on the healing of fractures of long tubular bones]. PMID- 4021413 TI - [Conduction anesthesia during operations on the lower and upper limbs]. PMID- 4021414 TI - [Characteristics of the diagnosis and treatment of peace-time thoraco-abdominal injuries]. PMID- 4021415 TI - [Blood supply of the limbs in cicatricial changes in tissue after trauma]. PMID- 4021416 TI - [Surgical tactics in gunshot foreign bodies of long duration in the lungs]. PMID- 4021417 TI - [Intraoperative and postoperative monitoring of blood circulation in autologous transplantation of toes to the hand]. PMID- 4021418 TI - [Local dynamometry in the early diagnosis of fractures of the navicular bone]. PMID- 4021419 TI - [Cholecystectomy in patients with bradyarrhythmic disorders and continuous electrocardiostimulation]. PMID- 4021420 TI - [Postoperative microstrabismus: performance accuracy in spatial depth]. AB - Thirty-six patients with postoperative microstrabismus (24 of them without or with only a slight amblyopia, 12 with severe unilateral amblyopia) and three control groups (normal binocular, long-term monocular, and inexperienced monocular subjects) were tested by their ability to hit 14 vertical sticks set in varied positions in a rectangular board, without any time limit during the first test and with time limits in the second and third tests. The evaluation shows that all 36 patients achieved considerably better results than any of the monocular subjects, but did not score as highly as normal binocular persons. PMID- 4021421 TI - [Measurement of stereoscopic vision in 6-year-old preschool children]. AB - Stereoacuity can be measured accurately in 6-year-old (pre-school age) children using a specially designed test. The values obtained, measured with stereo testers for long-range and close-range vision, do not differ significantly from those obtained in adults. Hence, it appears that the development of binocular vision must be terminated earlier than hitherto assumed. The limiting factor in stereo measurements at this age and with these methods is the degree of maturity of the children's mental and motor capabilities. PMID- 4021422 TI - [Carotenoid retinopathy. I. Morphologic and functional findings]. AB - Thirty patients who had undergone long-term treatment with carotenoids (max. 14 years and 336 g of carotenoids) were examined. Ophthalmoscopy revealed retinal crystals in 20 patients. The retinal crystals were usually located around the macula, forming a ring, and in one case they were even found in the macula itself. No deterioration of visual acuity or visual field defects were found, but there was a markedly dose-dependent prolongation of the duration of dark adaptation. PMID- 4021423 TI - [Differential light perception threshold of the visual field and ERG following operatively attached retinal detachment]. AB - After surgical treatment of retinal detachment with a spontaneously pigmented demarcation line the visual fields of twelve patients were tested. The increment threshold of all positions (determined with the Octopus automatic perimeter system) was compared with the reduction in the scotopic and photopic ERG amplitudes (determinated with the CEMIDA system). This reduction in the ERG amplitudes was evaluated using the difference between the amplitude of the ERG waves of the eye with cured retinal detachment and of the healthy fellow eye. No great correlation between the two parameters was found, but it appeared that a reduced mean increment threshold correlated with a reduction in the a-wave amplitude. PMID- 4021424 TI - [Extraction of foreign bodies in cases with complications]. AB - Analysis of surgical treatment of 186 patients with intraocular foreign bodies and concomitant complications such as cataract, opacity of the vitreous body, hemophthalmos, and endo-ophthalmitis. The authors employed a variety of surgical procedures to remove foreign bodies, with opticoconstructive operations such as phacoemulsification, lensectomy, and vitrectomy. Reliable data were obtained conforming the efficacy of these operations. A total of 178 foreign bodies were removed; 2 could not be extracted. Six foreign bodies were left in situ, since removal was contraindicated. In the majority of the patients visual acuity improved. The authors have developed a system of interventions for various combinations of intraocular changes and foreign bodies. PMID- 4021425 TI - [Endothelium protective effect of hyaluronic acid]. AB - In an experimental study the endothelia of porcine corneas were exposed to mechanical trauma under controlled conditions. Endothelial damage was caused by a polymethylmethacrylate (PMMA) plastic sphere shaped like the optical part of an intraocular implant. Two power settings were investigated. At the high power setting an average damage of 4.63 mm2 (+/- 1.33) was observed under saline, whereas application of hyaluronic acid 1% reduced the endothelial cell loss to 3.006 mm2 (+/- 0.87). At a low power setting the endothelial cell loss under saline was 2.18 mm2 (+/- 0.65); the average damage under hyaluronic acid was 0.55 mm3 (+/- 0.29). The results were statistically significant. The cell protective effect of a viscous substance against a mechanically shearing force was thus demonstrated in a biomechanical model. PMID- 4021426 TI - [Accidental bilateral asymmetric ruby laser maculopathy]. AB - A 19-year-old man sustained a bilateral coagulation of the macula caused accidentally by a ruby laser rangefinder mounted on a tank. Five days later vision was OD 0.7, OS 0.05; there was a distinct disk of coagulation of the retinal pigment epithelium with clumping of melanin granula, more in the left eye than in the right, and subretinal hemorrhage on the left. Visual improvement corresponded to the asymmetric morphologic findings: Within two months visual acuity in the right eye recovered to 1.0. In the left eye there was a temporary increase to 0.3, then permanent deterioration of vision to 0.05 OS. The macula of the left eye showed massive lipofuscein aggregation in the subretinal space. Fluorescein angiography after two months showed some hyperfluorescence, more in the left than in the right eye, but no fluorescein extravasation. The vision in the left eye is still 0.05 one year after the accident. PMID- 4021427 TI - [Radiotherapy treatment of malignant melanoma of the corneoscleral zone]. AB - Report on a case of malignant melanoma of the limbus and the neighboring cornea and conjunctiva. Excision of the tumor was not possible because of widely scattered cells in the cornea and conjunctiva. After evident progression of the tumor was observed, with signs of inflammation and prominence, radiotherapy was decided on. The melanotic area was irradiated with the strontium 90 applicator, with altogether 65 Gy. The central tumor region in the limbus was saturated with altogether 105 Gy. Four years later residual pigment cells were found in the limbus and the neighboring cornea and conjunctiva, without any signs of recurrence. PMID- 4021428 TI - [Clinical findings following a 32-year wearing time of a Ridley artificial lens]. AB - Clinical pathological findings 32 years after implantation of an artificial lens by Ridley himself are described. Changes were found in the cornea, anterior chamber, chamber angle, iris, retropupillary space, posterior segment and vitreous. The possible reasons for these complications are discussed and the clinical course is described. PMID- 4021429 TI - [Differential diagnosis and therapy of gigantopapillary conjunctivitis]. AB - If wearers of contact lenses present with secretion and incompatibility of the contact lens, simple ectropionation of the upper eyelids often is sufficient to diagnose a giant papillary conjunctivitis as the cause. This form of papillary hypertrophy affecting wearers of both hard and soft contact lenses is morphologically similar to vernal conjunctivitis, which should be considered in cases of corneal ulceration resistant to therapy. The histological difference between the two forms of papillary hypertrophy is that contact lens-induced giant papillary conjunctivitis shows remarkably less eosinophilic infiltration of the papillary stroma. Both forms of papillary hypertrophy seem to be based on a complex immunologic reaction. PMID- 4021430 TI - [Euphorbiae keratoconjunctivitis]. AB - This paper reports on 6 cases of keratoconjunctivitis caused by the latex of Euphorbiaceae, one of them with slight systemic intoxication. Phorbolesters are considered to be responsible for the toxicity of the latex of Euphorbiaceae, e.g., in the case of Euphorbia helioscopia, 12-Desoxyphorbol-13-phenylacetate-2-O acetate. Since all of the cases of keratoconjunctivitis Euphorbiae described here, as well as the majority of those cited in the literature, have resulted in a restitutio ad integrum, a benign course may be expected, even in cases of keratoconjunctivitis Euphorbiae with initially severe clinical pictures. PMID- 4021431 TI - [Oculo-oscillodynamography, a new procedure for the determination of ophthalmic artery blood pressure and ocular pulse curve analysis]. AB - OODG is a diagnostic method permitting assessment of ocular pulse curves and objective determination of blood pressures in the ophthalmic circulatory system (retinal and ciliary arterial blood pressures) simultaneously for both eyes, without dilatation of the pupils. Calibrated scleral suction cups pneumatically connected to a sensitive transducer are used to provide well reproducible ocular pulse recordings. The systolic retinal and ciliary arterial blood pressures and the diastolic ocular blood pressure are determined at artificially elevated IOPs from typical changes in the ocular pulse curves. PMID- 4021432 TI - Hepatobiliary scintigraphy and function test with 99mTc-N-pyridoxyl-5 methyltryptophan (99mTC-PMT). PMID- 4021433 TI - Hemoglobin A1 and hemoglobin A1c in elderly diabetics. PMID- 4021434 TI - Ferrets in biomedical research. PMID- 4021435 TI - A comparative study of the tapetum, retina and skull of the ferret, dog and cat. AB - Results of this investigation indicate that the ferret (Mustela putorius) closely resembles the dog (Canis familiaris) and should be a useful research animal alternative. The tapetum lucidum is a common structure present in the eyes of dogs, cats (Felis catus) and other nocturnal animals. Our study showed that this structure was present in ferret eyes. The color or reflection of the ferret and dog tapetum was remarkably reduced by the general fixation with glutaraldehyde. However, this color fading phenomenon was not observed in the cat tapetum. These observations led to this comparative study on several morphological, histochemical and biochemical parameters on mature ferrets, dogs and cats including: (1) the number of center tapetum cell layers, (2) thickness of center tapetum, (3) presence of a microtubule-like structure in each tapetal rod, (4) presence of electron-dense cores in tapetal rods after prolonged fixation in glutaraldehyde, (5) retention of reflection or color of tapetum after prolonged glutaraldehyde fixation, (6) zygomatic bones of eye orbits, (7) zinc content in tapetum, (8) cysteine in the tapetum, (9) cysteine sulfinic acid decarboxylase in liver, (10) thickness of retina from center tapetum, (11) anterior view of skull configuration, and (12) lateral view of skull configuration (jaw and teeth). Among these 12 parameters, ferret and dog were similar in the first nine points; ferret and cat were similar to each other only in the last two points. There was no difference in retinal thickness among these three animals. PMID- 4021436 TI - Measles virus encephalitis in ferrets as a model for subacute sclerosing panencephalitis. AB - Young adult ferrets were used as experimental animals to study subacute sclerosing panencephalitis (SSPE). When cells infected with cell-associated measles virus strains isolated from SSPE patients were inoculated intracerebrally (i.c.) into ferrets, they developed an acute encephalitis and died within 1 to 3 weeks without detectable antibody formation. Immunization with live measles vaccine 5 weeks before i.c. inoculation changed the course of the infection in about 50% of the ferrets. These animals developed a subacute encephalitis within weeks or months after inoculation. Cell-associated measles virus was isolated from their brains and high measles antibody titers were found in their sera, comparable to those in sera of SSPE patients. Measles virus specific immunoglobulins (IgG) were present in their brains and determination of IgG/albumin ratios indicated that antibodies were synthesized in the brain in response to the persistent measles virus infection. Measles specific oligoclonal IgG bands were found in the sera and spinal fluids of these animals. Therefore, subacute ferret encephalitis has virological and immunological characteristics in common with SSPE, indicating that it may serve as a model for the human disease. Other animal models of SSPE are described briefly. PMID- 4021437 TI - The ferret as a model for inner ear research. AB - Viral infections have long been suspected to be causative agents in a number of inner ear dysfunctions. With few exceptions, the virus has not been demonstrated as the direct agent leading to hearing loss and/or vertigo. Selective inner ear changes have been observed recently in sensory and nonsensory epithelial cells in the ferret model for Reye's syndrome after intranasal inoculation with influenza B combined with aspirin administration and the creation of an arginine deficiency. Such findings suggest that these agents act synergistically on the inner ear, particularly on cells that are metabolically active, and that the ferret may now be a useful model to examine the role of certain upper respiratory tract viruses implicated in inner ear disorders, singly and in combination with other agents that may cause metabolic alterations. PMID- 4021438 TI - Pulmonary physiology of the ferret and its potential as a model for inhalation toxicology. AB - Physiological measurements were made from anesthetized, tracheotomized, supine male ferrets. Six animals weighing 576 +/- 12 g, had tidal volumes (Vt) of 6.06 +/- 0.30 ml, respiratory frequencies (f) of 26.7 +/- 3.9 min(-1), dynamic lung compliance (CDYN) of 2.48 +/- 0.21 ml cmH2O(-1), pulmonary resistance (RL) of 22.56 +/- 1.61 cmH2O L(-1) sec. Pressure-volume curves from nine ferrets (including the above six) revealed almost infinitely compliant chest walls so that lung and total respiratory system curves were essentially the same. Total lung capacity (TLC) (89 +/- 5 ml) and functional residual capacity (FRC) (17.8 +/ 2.0 ml) were determined by gas freeing the lungs in vivo. The TLC of these ferrets was about the same as in 2.5 kg rabbits. Maximum expiratory flow-volume curves showed peak flows of 10.1 vital capacities (VC) sec(-1) at 75% VC and flows of 8.4 and 5.4 VC sec(-1) at 50% and 25% VC. No particular problems were encountered in making these measurements using conventional techniques available in laboratories capable of making pulmonary function measurements on rats and guinea pigs. Preliminary studies of airways reactivity showed equal increases in pulmonary resistance in response to equivalent challenges of aerosolized carbachol and histamine. Light and electron microscopic studies showed that the airways of ferrets are even more like those of humans than are the dog's. The ease with which physiological measurements can be made and the favorable aspects of the lung anatomy indicate the ferret may be more useful, as well as less expensive, than the dog for use in studies of pulmonary physiology and inhalation toxicology. PMID- 4021439 TI - Evaluation of ketamine, ketamine-xylazine and ketamine-diazepam anesthesia in the ferret. AB - Ketamine, ketamine-xylazine, and ketamine-diazepam were evaluated clinically in 15 ferrets, and safe dosage was determined for each. All of the three regimens provided excellent immobilization. However, muscle rigidity and incomplete analgesia were noted in ketamine alone and in ketamine-diazepam respectively. It was concluded that 25 mg/kg ketamine and 2 mg/kg xylazine intramuscularly provided acceptable analgesia, muscle relaxation, duration and smooth recovery, although cardiac arrhythmias were a concern and require careful observation. PMID- 4021440 TI - Adrenalectomy in the ferret. AB - A simple adrenalectomy technique is presented for the ferret (Mustela putorius furo). The adrenal glands were removed in two operations with an interim recovery period of approximately 1 week. The right adrenal should be removed first, as the surgery is complicated on that side by fascia which binds the adrenal to the inferior vena cava. Salt solution (1% NaCl) in place of water will maintain sodium balance. PMID- 4021441 TI - Restraint device for serial blood sampling of ferrets. AB - A device was designed that effectively restrained unanesthetized ferrets for serial blood sampling from the caudal artery. Materials used for construction were inexpensive and easily obtained. Fabrication was simple and rapid. PMID- 4021442 TI - Immunopathology of type I diabetes mellitus: an evolving concept. PMID- 4021443 TI - Morphologic and functional evidence for oxygen deficiency in the isolated perfused rat kidney. AB - Morphologic and functional studies were undertaken in the isolated rat kidney, perfused with an albumin-Krebs-Henseleit solution, to which 5% human erythrocytes and/or various amino acids had been added. Perfused only with the albumin-Krebs Henseleit solution, the kidneys displayed a characteristic pattern of cell necrosis after 2 hours of perfusion, which was confined to the interbundle region of the outer medulla and was not evident in either the cortex or the inner medulla. In the outer stripe only those proximal straight tubules (P3 segments) farthest from the vascular bundles were damaged. In the inner stripe only those thick ascending loops of Henle at the periphery of the vascular bundles escaped damage; all thick ascending loops of Henle lying farthest from the bundles were severely damaged. The number of damaged tubules increased toward the border to the inner medulla. Necroses in both segments, P3 and thick ascending loops of Henle, could be prevented by perfusion with the erythrocyte-albumin-Krebs Henseleit solution but not by the addition of glutathione, in the absence of erythrocytes. Perfusion with the erythrocyte medium also significantly improved glomerular filtration rate and sodium and glucose reabsorption. It is concluded that, in the isolated, erythrocyte-free perfused kidney, the oxygen content of the "arterial" vasa recta in the vascular bundles is only sufficient to supply the tubules in the immediate surroundings. Countercurrent exchange in the vascular bundles between arterial and "venous" vasa recta progressively lowers the arterial oxygen content as the inner stripe of the outer medulla is approached and with it the number of tubules receiving an adequate oxygen supply. PMID- 4021445 TI - Behavior of transplanted large granular lymphocyte leukemia in Fischer 344 rats. AB - The behavior of transplanted large granular lymphocyte leukemia was studied by isogeneic inoculation of 55 young F344 rats. A high percentage of transplants were successful, showing a dose-dependent latent phase followed by weight loss, exponential increase of tumor cells, and widespread infiltration. Serial passage of tumor cells appeared to increase malignancy by decreasing longevity. Grossly, there was splenomegaly, variable lymphadenopathy, and petechial hemorrhages on the lungs, lymph nodes, and brain. Diffuse infiltration of tumor cells caused morphologic changes identical with spontaneous large granular lymphocyte leukemia including splenic lymphoid depletion, hepatocellular necrosis, tumor cell erythrophagocytosis, and femoral medullary endosteal bone proliferation. Clinicopathologic features were also similar to spontaneous large granular lymphocyte leukemia. There was immune-mediated hemolytic anemia and thrombocytopenia, which coincided with development of leukemia, as well as hyperbilirubinemia and elevated serum enzymes, indicative of liver disease. It was concluded that isogeneic transplantation of large granular lymphocyte leukemia is not only highly successful but reproduces the pattern and clinical syndrome of the spontaneous tumor including the important paraneoplastic syndrome of hemolytic anemia and thrombocytopenia. PMID- 4021444 TI - Procoagulant activity in glomeruli and urine of rabbits with nephrotoxic nephritis. AB - A telescoped model of nephrotoxic nephritis in the rabbit, using guinea pig antiglomerular basement membrane IgG in rabbits preimmunized with guinea pig IgG, reproducibly induced crescentic nephritis. Procoagulant activity (PCA) was measured in sieve-isolated glomeruli that had been either sonicated or cultured for 48 hours. In both sonicated and cultured glomeruli PCA peaked on days 5 and 6. The time course for appearance of PCA corresponded precisely with the appearance of proteinaceous material containing fibrin in Bowman's space as measured by a light microscopic histologic scoring system and confirmed by immunofluorescence and electron microscopy. Glomerular PCA returned to baseline by days 9 and 10 in spite of progression of glomerular injury. PCA also appeared in urine. Urine PCA peaked on day 8 and persisted through day 12 when glomerular PCA had returned to baseline. Glomerular and urine PCA were characterized using human coagulation factor-deficient plasmas and antithromboplastin IgG. Both glomerular PCA and urine PCA were inhibited by antithromboplastin IgG, showing that thromboplastin (tissue factor) contributed to PCA. The PCA in glomerular sonicates was dependent on factor X, but independent of factor VII or Hageman factor, suggesting that factor VII was present. Following glomerular culture for 48 hours the PCA had changed and in some cases was dependent on Hageman factor, factor IX, and factor VII for full PCA expression. Urine PCA was uniformly Hageman factor dependent and sometimes independent of factors VII and X. No active thrombin was present. The forms of glomerular and urine PCA were, therefore, complex. They seemed to be primarily driven by thromboplastin but also appeared to require the presence of the intrinsic coagulation pathway for full expression of PCA. PMID- 4021446 TI - Secondary structure of endocrine amyloid: infrared spectroscopy of medullary carcinoma of the thyroid. AB - Infrared spectroscopic characteristics of deparaffinized tissue sections of the amyloid produced by medullary carcinoma of the thyroid confirm the presence of both beta-sheet and disordered conformations within the deposits. No evidence for alpha-helical structures is found. Amyloid produced by medullary carcinoma of the thyroid thus possesses secondary structural characteristics similar to amyloid of immunoglobulin origin. Infrared spectra were obtained directly from deparaffinized tissue sections, assuring that the chemical structure of amyloid in the recorded spectrum corresponds to that seen microscopically. This structure may or may not correspond to that in vivo, since fixation and dehydration may alter protein secondary structure. PMID- 4021447 TI - Activity and affect among the aged. PMID- 4021448 TI - Precursors of spatial ability: a longitudinal study among the Logoli of Kenya. PMID- 4021450 TI - Encoding of new versus old information by autistic children. AB - Research and literature on communication problems of autistic individuals have identified specific pragmatic deficiencies. This preliminary study focused upon describing autistic children's verbal performance in regard to the pragmatic ability of encoding new versus old information. Four autistic children with MLUs of 1.96-2.82 were videotaped on two occasions in interactions with their teachers or speech-language pathologists. All of the subjects' referential utterances, including referential echolalic utterances, were categorized as the encoding of new or old information. Two prominent means that speakers used for encoding new versus old information were examined: the encoding of new information through single-word utterances (i.e., a lexicalization strategy) and the use of contrastive stress to highlight new information in multiword utterances. The results revealed that the 4 subjects did encode new information through lexicalization in single-word utterances and through contrastive stress in multiword utterances. However, the subjects encoded old information almost as frequently as they encoded new information. The encoding of a new action or state change was marked relatively infrequently by the subjects, and they consistently produced repetitions of previously encoded information when they failed to offer new information to their listeners. The results are discussed in reference to cognitive processing patterns of autistic individuals. PMID- 4021449 TI - Israeli parents' role in emergencies. PMID- 4021451 TI - Relative translucency of ASL signs representing three semantic classes. AB - One variable that has been shown to facilitate sign learning is the perceived translucency between a sign and its gloss. Unfortunately, there is limited information regarding which signs or what types of signs are translucent for young children. The current investigation is an attempt to determine whether children and adults perceive different amounts of translucency in signs drawn from early sign teaching lexicons and representing three different semantic classes. Results indicate that 4- and 7-year-old children and adults perceive signs that represent action to be more translucent than signs representing nomination and signs that represent nomination to be more translucent than signs representing attribution. PMID- 4021452 TI - Using the miniature linguistic system in teaching syntax: two case studies. AB - Two language-delayed children received comprehension instruction on preposition object phrases using a miniature linguistic system format to structure generalization. Results indicated generalization not only to untreated two-word combinations, but also to comprehension of four-word phrases. In addition, there was some generalization of production of two- and four-word structures. PMID- 4021453 TI - Speech production and oral motor skill in an adult with an unrepaired palatal cleft. AB - The aim of this study was to identify maneuvers and strategies that enabled an adult speaker to produce "pressure" consonants intelligibly despite an open cleft of the palate. Dynamic palatometry indicated that this was achieved in part by increasing linguapalatal contact in stop sound production and narrowing the linguapalatal groove in sibilant sound production. These adaptations apparently enabled the talker to compensate for reduced air supply in a manner similar to that identified previously in responses of subjects with esophageal speech. Oral motor skill was examined in a nonspeech task that involved tongue tip placement at six points along the palate with and without visual feedback. This revealed precise control of the tongue even in the region of the cleft. Less accurate tongue placement skills were found in the central palatal region despite intactness of the palate. This supports the hypothesis that phonetic inventories of human languages are shaped by oral motor capabilities. PMID- 4021454 TI - Measurement and modification of speech naturalness during stuttering therapy. AB - This paper describes two studies that illustrate the utility of listener ratings of speech naturalness for measuring and modifying speech naturalness during a stuttering therapy program. The program involved 5 adolescent stutterers who were receiving an intensive treatment incorporating a prolonged speech procedure. In Study A, a clinician used a 9-point rating scale to score the speech naturalness of 1-min speaking samples each stutterer made at intervals over the course of the program. The results demonstrated predictable trends in speech naturalness during the program, but they also showed that natural sounding speech is not a predictable outcome of a procedure that removes stuttering, controls speaking rate, and exposes clients to transfer procedures. In Study B, 3 of the 5 stutterers participated in single subject experiments partway through their therapy program. These experiments were designed to assess the effect of regular feedback of speech naturalness ratings on the stutterer's spontaneous speech. The results showed that each subject's speech naturalness ratings could be modified toward a target level of speech naturalness. PMID- 4021455 TI - On the subject of subjects: suggestions for describing subjects in language intervention studies. AB - Recent child language intervention literature was analyzed to determine the content and consistency of subject descriptions. The amount and type of descriptive information varied widely both within and among journals. In view of the potential importance of such descriptions and the apparent lack of standards for acceptability, suggestions were developed and forwarded as a working model for describing language-handicapped children in intervention studies. PMID- 4021456 TI - Esophageal insufflation testing in nonlaryngectomized adults. PMID- 4021457 TI - Questioning the value of large N, multivariate studies. PMID- 4021458 TI - "No news is bad news". PMID- 4021459 TI - Role of iconicity in sign acquisition. PMID- 4021460 TI - Response to "Contemporary accounts of the cognition/language relationship". PMID- 4021461 TI - Effects of breathing high concentrations of oxygen on PWC170. PMID- 4021462 TI - Prediction of VO2max from the running performance in children aged 10-17 years. PMID- 4021463 TI - Pituitary and gonadal secretory variations and control mechanism during physical exercise. PMID- 4021464 TI - Body composition of successful Nigerian female athletes. PMID- 4021465 TI - Effects of feet cooling on pain, thermal sensation and cardiovascular responses. PMID- 4021466 TI - Some limitations of exercise testing. PMID- 4021467 TI - Cardiac size and distance running performance. PMID- 4021468 TI - Interval training: the effects of a 12-week programme on elite, pre-pubertal male soccer players. PMID- 4021469 TI - Cardiorespiratory responses to "aerobic dance". PMID- 4021470 TI - Sleep disruption following a marathon. PMID- 4021472 TI - Muramyl dipeptide and polymorphonuclear leukocyte chemotaxis in vitro. AB - Muramyl dipeptide (MDP) is an immunostimulatory agent that has been shown repeatedly to provide protection against the effects of some forms of experimental surgical infection. The mechanisms of this protection are incompletely understood, and in order to further define them, the impact of MDP upon in vitro polymorphonuclear (PMN) leukocyte chemotaxis was examined in the presence of both normal and opsonic depleted serum. We have also evaluated the effect of MDP as a chemoattractant itself and the response of neutrophils along with MDP to a standard chemoattractant, n-formyl-L-methionyl-L-leucyl-L-phenyl alanine (FMLP), using the agarose assay for chemotaxis. MDP has weak but significant chemotactic activity itself, with a peak effect at a concentration of 5 X 10(-8) micrograms/ml for neutrophils. These effects are enhanced by the addition of 10% serum. MDP more strongly enhances neutrophil chemotaxis to FMLP. The enhancement of chemotaxis may be a factor in the protection that MDP exerts against some experimental bacterial challenges. PMID- 4021471 TI - Myocardial oxygen consumption with isoproterenol versus calcium chloride in hypocalcemic ventricular failure in dogs. AB - In 30 dogs on right heart bypass we compared the effects of isoproterenol with those of calcium chloride on myocardial oxygen consumption and on left ventricular function in the setting of ventricular depression produced by ionized hypocalcemia. In 22 dogs (Groups A and B) either isoproterenol or calcium chloride was infused, left ventricular function curves were generated, and end diastolic pressure vs segment length plots were obtained. In 8 dogs (Group C), with initial hypocalcemia, both isoproterenol and calcium chloride were infused separately in random order to produce an equal decrease in left ventricular end diastolic pressure at constant mean aortic pressure, heart rate, and cardiac output. Myocardial oxygen consumption and indices of left ventricular function were obtained. In Groups A and B, both drugs, when administered to the ventricle depressed by hypocalcemia, displaced left ventricular function curves upward and to the left. Left ventricular stroke work at constant left ventricular end diastolic pressure increased (from 13.0 +/- 1.3 to 31.2 +/- 2.3 g X m for isoproterenol; from 13.9 +/- 2.5 to 32.5 +/- 2.5 g X m for calcium chloride). In Group C, there were no significant differences between left ventricular end diastolic pressure, end-diastolic internal diameter, myocardial oxygen consumption, or peak left ventricular dP/dt in the hypocalcemic periods preceding isoproterenol and calcium chloride infusion. When the two drugs caused matched decreases in left ventricular end-diastolic pressure (-7.4 +/- 0.5 cm H2O for isoproterenol; -7.3 +/- 0.8 cm H2O for calcium chloride) there were similar decreases in end-diastolic internal diameter. However, isoproterenol was associated with a significantly greater (P less than 0.001) myocardial oxygen consumption (13.7 +/- 0.4 ml X 100 g-1 X min-1) than calcium chloride infusion (11.9 +/- 0.4 ml X 100 g-1 X min-1), as well as a greater peak left ventricular dP/dt (P less than 0.005). PMID- 4021473 TI - Functional and histologic changes in vein grafts exposed to crystalloid potassium cardioplegic solution. AB - A canine external jugular vein to iliac artery interposition model was devised to evaluate the potential deleterious effects of cold potassium cardioplegic solution exposure to saphenous vein grafts during aortocoronary bypass procedures. The right jugular vein was harvested from 11 animals and halved, one segment being perfused with 1 liter of normal saline solution (NS) at 4 degrees C over a period of 31.7 +/- 2.5 min at a perfusion pressure of 50.5 +/- 2.6 mm Hg, and the other segment perfused with 1 liter of crystalloid potassium cardioplegic solution (CP) at 4 degrees C over a period of 24.8 +/- 3.2 min at a perfusion pressure of 53.0 +/- 1.5 mm Hg. The measured differences in the perfusion times and pressures were not significant at P less than 0.05. The grafts were then interposed into the iliac artery systems of their respective animals, and transgraft pressure gradients were measured by direct needle puncture technique and found to be 12.6 +/- 5.9 mm Hg for the CP-treated grafts and 19.9 +/- 9.6 mm Hg for the NS-treated grafts. At the time of graft harvest 7.4 +/- 0.23 months later transgraft pressure gradients were again measured and found to be 2.5 +/- 1.8 mm Hg for the CP-treated and 2.9 +/- 1.7 mm Hg for the NS-treated grafts.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4021474 TI - Prevention of suppressed cell-mediated immunity in burned mice with histamine-2 receptor antagonist drugs. AB - Thermal injury has been shown to suppress many aspects of both specific and nonspecific immune responses. We investigated the effect of two histamine H-2 antagonist drugs on cell-mediated immunity in burned mice, utilizing a method of quantitating the degree of contact sensitivity elicited to the antigen. 2,4 dinitrofluorobenzene (DNFB). Following sensitization by painting the abdomen with DNFB, animals were challenged 5 days later by painting the ears; subsequent ear swelling is a sensitive and reproducible measure of cell-mediated immunity. We have previously demonstrated that burned mice are maximally immunosuppressed 10 to 14 days following burn injury. In the present study we found that daily intraperitoneal administration of appropriate doses of the H-2 antagonists cimetidine (2 and 10 mg/kg/day) and ranitidine (2 and 10 mg/kg/day) resulted in maintenance of normal cell-mediated immunity in burned animals. Neither a lower dose of ranitidine (0.2 mg/kg/day) nor higher doses of cimetidine (20 and 50 mg/kg/day) restored immunity, and diphenhydramine, an H-1 antagonist, had no effect. There was no augmentation of contact sensitivity in unburned mice treated with cimetidine. The immunorestorative effect is probably secondary to antagonism of histamine H-2 receptors on suppressor T lymphocytes, and may reflect increased suppressor cell activity in burned mice; however, other mechanisms may be involved. PMID- 4021475 TI - Liposome uptake by melanoma: in vitro comparison with hepatocytes. AB - Liposomes are artificially generated vesicles entrapping aqueous solutions within lipid bilayer membranes. A major potential use of liposomes is for the delivery of antineoplastic agents to malignant tissue. However, liposome-cell interactions with both normal and neoplastic cells must be characterized in vitro to identify neoplastic tissues for which this approach may be most applicable in vivo. In this study, mouse melanoma-liposome interactions were examined in vitro. Small, unilamellar vesicle liposomes of three different phospholipid-cholesterol compositions were synthesized incorporating an aqueous phase fluorescent marker. Mouse melanoma had a significantly greater affinity for phosphotidylcholine cholesterol liposomes than did mouse hepatocytes, as determined by comparing quantities of free intracellular 6-carboxyfluorescein in cells after a 15-min incubation with each of the three different liposome preparations (P less than 0.001). In addition, the efficiency of liposome internalization, calculated as the percentage of total cell-associated 6-carboxyfluorescein present as free, intracellular 6-carboxyfluorescein, was significantly greater for melanoma than for hepatocytes with all three liposome preparations (P less than 0.05). Therefore, in vitro liposome uptake by melanoma depends on lipid characteristics of the liposome preparation. Because melanoma uptake of liposomes appears to be a very efficient process in vitro, liposomes may be a useful vesicle for delivery of antineoplastic agents to melanoma in vivo. PMID- 4021476 TI - Effect of coronary artery occlusion on myocardial protection by retroperfusion of cardioplegic solutions. AB - Coronary artery stenoses impede delivery of cardioplegic solutions infused through the aortic root. Therefore, the efficacy of retroperfusion of cardioplegic solution through the coronary sinus was assessed in dogs subjected to cold, potassium cardioplegic arrest. Group I (N = 15) had the left anterior descending (LAD) coronary artery occluded throughout ischemia while Group II (N = 15) had a patent LAD. Transmural biopsies of both the left ventricular (LV) apex and right ventricle (RV) were assayed for adenosine triphosphate (ATP) and creatine phosphate (CP). Regional wall temperatures were sequentially monitored. The time from aortic cross-clamping to electrical arrest varied widely, but the mean arrest time of each group was similar (174 +/- 22 vs 175 +/- 28 sec). (table; see text) Comparable depletion of ATP stores (vs preischemia) occurred in each ventricle regardless of coronary artery patency. Similarly, CP stores were depleted 60-72% (P less than 0.01) during ischemia. Mean temperatures during arrest of the RV and LV (17.2-19.5 degrees C) did not differ and were not affected by LAD occlusion. Coronary venous resistance remained constant with repetitive infusions. These data suggest that myocardial protection with coronary sinus retroperfusion is independent of arterial patency, but is suboptimal, perhaps due to the prolonged time needed to induce ventricular arrest. PMID- 4021477 TI - Specific binding of oestradiol to guinea-pig prostate cytosol and nuclear fractions. AB - A high affinity (Kd approximately 0.15 nM), saturable oestradiol binding site, which is specific for natural and synthetic oestrogens has been identified in guinea-pig prostate cytosol fractions. The binding site is protein in nature (heat- and protease-sensitive) and has a sedimentation coefficient of approx. 8S on glycerol gradients. A high affinity (Kd approximately 0.16 nM), saturable oestradiol binding site was also identified in salt-extracted (0.5 M KC1) nuclear fractions. The optimum incubation conditions for measuring the cytosolic and nuclear oestradiol binding sites were determined to be 20 h at 4 degrees C. Saturation analysis studies revealed that following oestrogen treatment of intact animals, approx. 80% of the specific oestradiol binding sites in prostatic cytosol fractions were transferred into the nucleus. The presence of a specific oestradiol binding protein with characteristics of an oestrogen receptor in the guinea-pig prostate, is consistent with oestrogen having biological activity in this tissue. In view of the abundance of stroma in the prostate of this species, and the consistent finding that the stroma of male accessory sex tissues is oestrogen sensitive, the guinea-pig may be an appropriate experimental animal for further investigating the role of oestrogen in the growth and development of the prostate. PMID- 4021478 TI - Interaction of chick oviduct progesterone receptor with immobilized aurintricarboxylic acid. AB - Aurintricarboxylic acid (ATA) was immobilized on Sepharose 4B via a carbodiimide coupling mechanism. A majority of the chick oviduct progesterone receptor was retained on the affinity resin and could be recovered upon washing the column with buffer containing free ligand or 3 M guanidine-HCl. The [3H]progesterone receptor complex retained its integrity following the chromatography on ATA Sepharose as judged by sedimentation analysis. The procedure allowed significant purification of progesterone receptor: SDS-polyacrylamide gel electrophoresis of the purified preparation revealed elimination of many peptide bands present in the cytosol prior to ATA-Sepharose chromatography. The technique thus has a clear potential in characterization and purification of progesterone receptor. PMID- 4021479 TI - Oxygen dependence of oestrogen production by human placental microsomes and cultured choriocarcinoma cells. AB - The oxygen dependence of oestrogen (oestrone and 17 beta-oestradiol) formation from androstenedione and testosterone was studied in term human placental microsomes and in cultured human choriocarcinoma cells (BeWo line). Incubations were performed under various steady-state oxygen concentrations and the production of oestrone and 17 beta-oestradiol quantitated by specific radioimmunoassays. The aromatization of C19-steroids by both placental microsomes and choriocarcinoma cells was shown to be oxygen dependent over a wide range of O2 concentrations. The results indicate that placental oxygenation may be a critical factor in determining oestrogen production in vivo. Therefore, impaired oestrogen biosynthesis due to hypoxia could be an important factor in a variety of physiological and pathological conditions. PMID- 4021480 TI - Effect of glucocorticoids on the turnover rate of actin and myosin heavy and light chains on different types of skeletal muscle fibres. AB - The catabolic action of glucocorticoids on the molecular level of the two main muscular proteins, myosin and actin, was found to depend on the type of muscle fibres. The synthesis rate of actin and myosin heavy chain was decreased in all types of muscle fibres, and in myosin light chain only in the slow-twitch red fibres. The turnover rate of actin and myosin heavy chain was also found decreased in all types of muscle fibres. The myosin light chains turned over more rapidly in dexamethasone-treated than in the control rats in all types of muscle fibres except in the case of the slow-twitch red ones as was shown by single and double isotope methods. Dexamethasone treatment enhanced the urinary 3 methylhistidine excretion in rats by 60%. PMID- 4021481 TI - Intestinal absorption of oestrone, oestrone glucuronide and oestrone sulphate in the rat in situ--I. Importance of hydrolytic enzymes on conjugate absorption. AB - The biliary excretion of steroid after administration of [3H]oestrone ([3H]E1), [3H]oestrone glucuronide ([3H]E1G) and [3H]oestrone sulphate ([3H]E1S) into the hepatic portal vein of anaesthetized rats was very rapid with more than 70% of E1S and greater than 80% of E1 and E1G excreted in the first 30 min. There was a lag period in the biliary excretion of E1S, this was less apparent with E1 and absent with E1G. Biliary excretion accurately reflects the amount of steroid in the portal circulation and was therefore used as an assessment of absorption from the gastrointestinal (GI) tract. Absorption (as judged by excretion in bile) was least after administration of each steroid into the stomach. The extent of absorption correlated well with the lipophilicity of the steroids as shown by their relative partition coefficients between n-octanol and pH 6.5 phosphate buffered saline (E1 greater than or equal to E1S greater than or equal to E1G). There was no significant difference in excretion profile when the steroids were given into the caecum (at 5 h, E1, 46.3 +/- 9.1%; E1G, 42.2 +/- 14.5%; E1S, 39.9 +/- 7.1%). The similarity, despite marked differences in physicochemical properties, suggested conjugate hydrolysis to the parent steroid. In contrast, after administration into the small intestine, excretion of E1 was very rapid and was maximal at 1 h (72.5 +/- 8.0%); E1G showed a near-linear excretion rate (1 h, 14.4 +/- 3.0%; 5 h, 80.0 +/- 11.7%), whereas in comparison E1S excretion was low (1 h, 12.1 +/- 2.4%; 5 h, 36.9 +/- 2.7%). The involvement of hydrolytic enzymes in conjugate absorption was assessed. Ampicillin pretreatment (200 mg/kg/day for 2 days) reduced the absorption of E1G from both the proximal and distal small intestine (by approximately 50%) but had no effect on the absorption of E1S. There was, therefore, evidence that quantitative absorption of E1G requires prior hydrolysis (by mammalian and/or microbial enzymes) but intact absorption of E1S from this region of the tract was implicated. Ampicillin pretreatment reduced the absorption of both conjugates (greater with E1S) from the caecum; hydrolysis clearly precedes absorption from the caecum. The above findings were supported by an in vitro study which showed that ampicillin pretreatment abolished the hydrolysis of E1S by caecal contents but only partially reduced the hydrolysis of E1G. The presence of mammalian glucuronidase enzyme may account for this difference. PMID- 4021482 TI - Pituitary progesterone 5 alpha-reductase: solubilization and partial characterization. AB - The microsomal progesterone 5 alpha-reductase activity from female rat anterior pituitary has been solubilized and partially characterized with regard to some of its kinetic and physical properties. The solubilization of progesterone 5 alpha reductase has been achieved through the use of either an n-octyl glucoside (OG) KCl- or a digitonin-KCl-extraction. The total yield and specific activity of solubilized enzyme activity is greater using the OG-KCl method. Kinetic analyses of microsomal and OG-KCl-solubilized progesterone 5 alpha-reductase have indicated that both of these preparations exhibit a similar apparent Km for progesterone (microsomal Km = 117 +/- 12 nM; solubilized Km = 123 +/- 11 nM), suggesting that the solubilization procedure does not appreciably alter the kinetic behavior of this enzyme activity. The OG-KCl-extracted progesterone 5 alpha-reductase activity also appears quite stable, since essentially no enzyme activity is lost following dialysis at 4 degrees C for 22 h. In addition, the activity of the solubilized-dialyzed enzyme preparation can be slightly stimulated via the addition of phospholipids. Studies on the properties of the microsomal enzyme activity have indicated that this preparation is unaffected by metal chelators (EDTA or EGTA) but can be completely inhibited by the powerful sulfhydryl blocking agent p-chloromercuribenzoic acid. An evaluation of the possible role of flavins (as a hydride carrier between NADPH and the steroid) has shown that progesterone 5 alpha-reduction is inhibited by high levels of flavins and flavin analogs. PMID- 4021483 TI - Postnatal development of cholesterol ester hydrolase activity in the rat adrenal. AB - In certain circumstances the activity of cholesterol ester hydrolase (CEH) activity is believed to be rate-limiting for corticosterone production by the adrenal. The principal aim of the current study was to determine whether the activity of CEH displays a developmental increase in the infant rat which could, in part, account for the marked increase in serum corticosterone which begins at the end of the second postnatal week. The data show that the specific activity of CEH (units/mg cytosolic protein) during development is actually a mirror image of the pattern seen for serum corticosterone, i.e. CEH activities are high when serum corticosterone concentrations are low and then fall when serum corticosterone is rising. Even when total activities of CEH in the adrenal were calculated, there was no increase in parallel with the initial rise of serum corticosterone. At each age studied, stressed pups displayed significant increases of serum corticosterone; however, their CEH activities were no different from those in the non-stressed littermates. It is concluded that the activity of CEH is not the rate-determining factor for the developmental surge of basal concentrations of serum corticosterone nor for stress-induced elevation of corticosterone during the developmental period. A second aim of the current study was to address the more general question of whether steroidogenesis in the developing adrenal is limited by substrate supply. Measurement of the cholesterol content of adrenal mitochondria showed no ontogenic increase, suggesting that substrate supply, from any source, is not rate-limiting for steroidogenesis at these ages. PMID- 4021484 TI - The side-chain cleavage of cholesterol sulfate--I. The effect of adrenodoxin on the binding of cholesterol sulfate to cytochrome P-450scc. AB - Difference spectroscopy was used to measure the binding of cholesterol sulfate (CS) to cytochrome P-450scc. The uncomplexed cytochrome and the complex of the cytochrome with adrenodoxin (ADX) were both titrated with CS in order to test whether ADX increased the affinity of the cytochrome for the sterol sulfate. The addition of ADX to the cytochrome had different effects on the binding of the sterol sulfate depending on several factors including: (1) The method of preparation of the cytochrome P-450scc, (2) The concentration of cytochrome P 450scc, (3) The method by which CS was suspended in aqueous solution, and (4) Whether or not the solutions of cytochrome contained non-ionic detergents. The results of this study suggest that the method of isolation of cytochrome P 450scc, and non-ionic detergents, greatly modulate the apparent affinity of cytochrome P-450scc for CS. In the absence of detergents the addition of adrenodoxin to dilute solutions of cytochrome P-450scc appears to enhance only slightly (1- to 2-fold) the affinity of the cytochrome for the sterol sulfate. PMID- 4021485 TI - Metabolism of unsaturated bile acids and androstanes by human faecal bacteria. AB - The metabolism of unsaturated bile acids and androstanes by mixed human faecal cultures has been studied. The reactions observed were mainly reductive. Unsaturated 4-ene-3-oxo and 1,4-diene-3-oxo bile acids were reduced in Ring A. 5 beta-3-Oxo bile acids were reduced to 5 beta-3-hydroxy bile acids. 4-Ene, 1,4 diene and 4,6-diene-3,17-dioxo-androstanes were reduced in Ring A with concomitant reduction of oxo groups to hydroxyl groups. The Gram-negative facultative anaerobic faecal bacteria are implicated in the reductive process, whilst the genus Clostridium does not appear to be important. Inclusion of menadione, a synthetic form of vitamin K, retards the reductive process. PMID- 4021486 TI - Comparison of the receptor binding properties of nandrolone and testosterone under in vitro and in vivo conditions. AB - Previous in vitro binding studies with androgen receptors in rat seminal vesicles (Toth M. and Zakar T., J. steroid Biochem. 17 (1982) 653-660) have shown that the difference in the effects of nandrolone (N) and testosterone (T) is caused by the fact that 5 alpha-reduction increases the affinity of T and decreases the affinity of N. We confirmed this result using androgen receptors in rat prostate and intact human MCF-7 cells. We also analysed the receptor binding properties of N, T, dihydronandrolone (DHN) and dihydrotestosterone (DHT) in vivo following a combined 2-h infusion of a physiological dose of [3H]T and the same dose of [3H]N in castrated male rats, which permitted a direct comparison of the accumulation of [3H]N, [3H]T, [3H]DHN and [3H]DHT in different sub-cellular fractions of various tissues. There was a considerable accumulation of radioactivity in the liver, but no retention of active compounds. In the prostate there was a preferential retention of [3H]DHT over [3H] DHN in the receptor fractions whereas in thymus, spleen and muscular tissues [3H]N and [3H]T were retained in equal amounts. The kidney showed a preferential retention of [3H]N over [3H]T. The present results explain the relatively strong effect of nandrolone compared to that of testosterone on target tissues devoid of 5 alpha-reductase activity (e.g. muscular tissue) compared to its relatively weak effect on tissues with a relatively high 5 alpha-reductase content (e.g. prostate). PMID- 4021487 TI - The radioimmunoassay of pregnanetriol 3 alpha-glucuronide. AB - The hapten (5 beta-pregnane-17,20 alpha-diol-3 alpha-yl glucuronide) required to develop the radioimmunoassay was synthesized by an unambiguous chemical synthesis. An immunogenic complex was synthesized by coupling bovine serum albumin (BSA) to the glucuronide by mixed acid anhydride reaction. The immunogenic complex was used to induce the formation of specific antibodies in rabbits. In addition, the required radioligand [6,7-3H]5 beta-pregnanetriol 3 alpha-glucuronide was prepared with appropriate specific radioactivity. The characteristics of the antibody were determined with regard to specificity and sensitivity and the precision and accuracy of the assay method established. As applied to urine samples this method is superior to existing procedures in that they avoid the hydrolysis step and can be used directly on diluted urine. Examples have been given of useful application of this technique in clinical practice. PMID- 4021488 TI - Testosterone secretion is severely impaired after hepatectomy in rat, dog and man. AB - In 90%-hepatectomized rats, the plasma testosterone level (0.34 +/- 0.07 ng.ml, mean +/- SEM) is significantly lower (P less than 0.001) than in sham operated male rats (1.7 +/- 0.26 ng.ml, mean +/- SEM). In dogs, after 90% hepatectomy, the mean plasma testosterone concentration fell to 1/10 of the plasma testosterone level measured in sham operated animals either 24 or 72 h after surgery. In hepatectomized men, plasma testosterone is markedly decreased in contrast to what is observed after duodeno-pancreatectomy performed under the same conditions of anesthesia. These results suggest that 90% hepatectomy severely alters the Leydig cell function. PMID- 4021489 TI - Characterization of non-liganded glucocorticoid receptor in rat liver cytosol using indirect competitive enzyme-linked immunosorbent assay. AB - We have previously shown that the purified or unfractionated cytosolic, activated glucocorticoid receptor of rat liver consists of a polypeptide with a Stokes radius of approximately 6 nm, a sedimentation coefficient of 4S and a molecular mass of approximately 90,000 Daltons. We have confirmed previous observations by other authors that if sodium molybdate is introduced into the cytosol preparation buffer the non-activated glucocorticoid receptor appears as an 8 nm, 9S species with an apparent molecular mass of 330,000 Daltons. In order to study the physicochemical parameters of the glucocorticoid receptor prior to ligand binding, we have used an enzyme-linked immunosorbent assay (ELISA) based on antibodies raised in rabbits against the purified activated glucocorticoid receptor. In isotonic buffer, the non-liganded glucocorticoid receptor was shown to have a Stokes radius of 6 nm in the absence and 8 nm in the presence of molybdate. Furthermore, experimental conditions known to result in activation of the glucocorticoid receptor complex (increased ionic strength, increased temperature) did not lead to activation of the 6 nm non-liganded glucocorticoid receptor as judged from the lack of binding of the treated, non-liganded receptor to DNA-cellulose. The existence of both 6 and 8 nm forms of nonactivated, non liganded glucocorticoid receptor in vitro suggests that dissociation of an 8 nm form to a 6 nm form, if it occurs in vivo, is probably not the only molecular event constituting the activation of the glucocorticoid receptor. PMID- 4021490 TI - A new radioimmunoassay for serum 16 alpha-hydroxyandrost-4-ene-3,17-dione with specific antiserum. AB - A radioimmunoassay system for serum 16 alpha-hydroxyandrost-4-ene-3,17-dione was developed with the use of rabbit antiserum against 16 alpha-hydroxyandrost-4-ene 3,17-dione-3-(O-carboxymethyl)oxime which was conjugated with bovine serum albumin. The antiserum was highly specific for 16 alpha-hydroxyandrost-4-ene-3,17 dione, with cross reactions to other steroids being less than 0.8% except for androst-4-ene-3,17-dione(3.4% cross reaction). Use of LH-20 column chromatography, however, clearly separated these two steroids. Pregnancy sera were measured with this assay system after an addition of labelled internal standard, extraction and separation by column chromatography. The lower limit of detection for 16 alpha-hydroxyandrost-4-ene-3,17-dione was 2 pg/tube. The mean recovery rate of the added standard was 98.3 +/- 8.8% (mean +/- SE). Intra- and inter-assay coefficients of variation were 8.6% (n = 6) and 12.1% (n = 7), respectively. PMID- 4021491 TI - Further characterization of the estrogen binding macromolecule in human pancreas. AB - The estrogen binding protein in human pancreas has been purified from pancreatic cytosol by chromatography on Concanavalin-A-Sepharose and hydroxyl-apatite followed by ion-exchange chromatography carried out using a fast-protein liquid chromatography apparatus (FPLC). The purified protein, still able to bind labelled [3H]estradiol, appeared as one single band corresponding to 31 K in SDS gel electrophoresis. Total amino acid analysis revealed high levels of histidine, glutamic acid and leucine. The capacity of the purified protein to bind estrogens could be increased more than 4-fold by addition of a cytosolic factor, probably being a small peptide, that is present in crude cytosol, but lost during the purification procedure. The iodinated protein does not bind to DNA-cellulose or phosphocellulose, and shows no similarities to estrogen receptor proteins. PMID- 4021492 TI - Hormonal effects on the estrogen receptor system in the epididymis and accessory sex organs of sexually immature rabbits. AB - The epididymis and male accessory sex organs (vesicular gland, prostate, and bulbourethral gland) of sexually immature rabbits contain a functional estrogen receptor system which is regulated in an organ-specific manner by various hormones. In both intact and castrated animals, acute estrogen challenge causes depletion of estrogen receptor from the cytosolic fraction and its appearance in the nuclear fraction of these tissues. A considerable amount of unoccupied nuclear receptor was detected both before and after estrogen challenge. An estrogen-activated, receptor-processing mechanism is operable in these organs since chronic treatment (daily for 14 days) with estradiol benzoate modified the levels of total estrogen receptor, and altered the relative amounts of occupied to unoccupied nuclear receptor present following estrogen challenge. Chronic treatment with estradiol benzoate, Tamoxifen, and testosterone propionate (alone and in combination) had differential, organ-specific effects on the ability of subsequent estrogen challenge to cause accumulation of nuclear receptor. The vesicular gland was the most responsive to estrogen treatment and the bulbourethral gland the least responsive. PMID- 4021493 TI - Time course of anterior pituitary estrogen receptor after low 17 beta-estradiol doses in ovariectomized rats. AB - The present paper describes the effect of three 17-beta-estradiol (E2) doses (1, 10 and 500 ng E2/kg) on the cytosolic and nuclear estrogen receptor content of anterior pituitary (Ap) of ovariectomized rats. The estrogen receptors were measured by [3H]E2 exchange in cytosol and crude nuclear fractions. Two hours after the administration of 10 or 500 ng E2/kg the Rc showed a depletion to 20 30% of preinjection level. The 1 ng E2/kg dose did not provoke any Rc depletion. The Rc replenishment was completed 5 h after injection of 10 ng E2/kg, but it was delayed to 10 h after injection of 500 ng E2/kg. An increased amount of Rc over the control levels was produced by 1 and 10 ng E2/kg doses, but not by the 500 ng E2/kg. The Rn level in Ap increased significantly after all E2 doses, and their highest levels were similar for 1, 10 and 500 ng E2/kg. These results suggest that some estrogenic responses like synthesis of the estrogen receptor proteins, can be elicited without previous significant Rc depletion. The relationships between Rc and Rn in Ap suggest an autoregulatory mechanism for the control of the cellular level of unbound estrogen receptors, that can be altered by the exogenous E2. PMID- 4021494 TI - The role of estrogens on the proliferation of human breast tumor cells (MCF-7). AB - The cloned human breast tumor cell line C7MCF7-173 behaved as an estrogen dependent tumor in the nude mice. In contrast, E2 added to serum-less media did not increase the multiplication rate of these cells over the values obtained in the control cultures. Media supplemented with charcoal-dextran stripped (CD) human female serum (FHS) resulted in inhibition of cell proliferation in a concentration-dependent pattern (40% = 20% greater than 10% greater than 5% greater than 2.5%). E2 addition to all but the 2.5% CDFHS significantly increased the proliferation rate of these cells. The E2 concentration required to attain maximal proliferation rate increased as the serum concentration of the medium increased (e.g. 3 X 10(-11)M for 10% CDFHS, 3 X 10(-10)M for 40% CDFHS). E2 concentrations higher than the one needed to achieve maximal proliferation rate resulted in decreased cell yields (shut-off mechanism). Similar effects were obtained with synthetic and other natural estrogens. CD fetal bovine serum (FBS) also inhibited the proliferation of C7MCF7-173 cells; however, at similar concentration the inhibitory effect of CDFHS was more potent than the one obtained with CDFBS. The addition of "growth factors" (insulin, Epidermal Growth Factor and transferrin) and non-estrogenic steroids to 10% CDFHS failed to overcome the inhibitory effect of this serum. These results suggest that: (1) human and fetal bovine sera contain a specific inhibitor of the proliferation of E2-sensitive cells (estrocolyones), and (2) E2 promotes cell proliferation by neutralizing this inhibitor. PMID- 4021495 TI - Estrogen receptor in chicken oviduct: receptor dissociation kinetics and transformation. AB - Cytosolic and nuclear estrogen receptor forms of chicken oviduct have been studied by (1) measuring hormone dissociation kinetics and by (2) sucrose density gradient analysis on high salt gradients. Estradiol dissociates from the receptor in chicken oviduct cytosol at 22 degrees C following a two-phase exponential process. The fraction of receptor with a fast dissociation rate (k = 120 X 10(-3) min-1) decreases as a function of the pre-incubation at 22 degrees C; after prolonged pre-incubation only the slowly dissociating (k = 12.3 X 10(-3) min-1) form remains. Dissociation of moxestrol, a synthetic estrogen with a higher affinity, from the cytosol receptor at 30 degrees C is similar, showing a transition of a fast dissociating form (k = 120 X 10(-3) min-1) to a slowly dissociating form (k = 7.6 X 10(-3) min-1) as a result of pre-incubation at 30 degrees C. A concomitant temperature-dependent shift of the estrogen receptor from a 4.8 S to a 6.1 S form was observed with moxestrol but not with estradiol as a ligand. Sodium molybdate (20 mM) and NaSCN (400 mM) inhibit the temperature dependent increase in sedimentation coefficient, but molybdate allows the formation of a receptor form which shows intermediary dissociation kinetics. Estrogen receptor, precipitated with ammonium sulfate (0-35%) shows monophasic dissociation kinetics of estradiol (k = 39.5 X 10(-3) min-1) and for moxestrol (k = 10.8 X 10(-3) min-1), suggesting full receptor activation only with moxestrol as a ligand. Moxestrol-receptor complexes obtained by ammonium sulfate precipitation sediment at 0 degree C at 4.8 S. Only after subsequent incubation at 30 degrees C a shift from 4.8 S to 5.9 S is observed, suggesting that the formation of the slowly dissociating form of the receptor may precede the formation of a stable transformed receptor complex. The nuclear estrogen receptor with estradiol as a ligand shows biphasic dissociation kinetics at 22 degrees C (k = 70 X 10(-3) min-1; k = 14.0 X 10(-3) min-1). The ratio of both components (1:1) does not change after preincubation of the nuclear receptor extract at 22 degrees C. Moxestrol dissociates from the nuclear receptor at 30 degrees C monophasically with a slow rate (k = 6.1 X 10(-3) min-1), suggesting that it is extracted as an activated hormone-receptor complex.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 4021496 TI - Androgen metabolism in tissue recombinants composed of adult urinary bladder epithelium and urogenital sinus mesenchyme. AB - Epithelium of the adult mouse urinary bladder (BLE) was experimentally combined with mesenchyme of the urogenital sinus (UGM) and grown in intact male hosts to produce prostate-like glandular structures. To determine the extent to which the BLE is altered in a functional sense by inductive influences from UGM, investigations into the in vitro metabolism of tritiated testosterone (T) were undertaken. An isocratic high performance liquid chromatographic (HPLC) method was developed in order to separate the metabolites of T in mouse bladder, prostate and UGM + BLE tissue recombinants. Using a C-18 reversed phase column and a tetrahydrofuran (20): methanol (40): H2O (40) mobile phase, efficient and rapid separation of T, dihydrotestosterone, 3 alpha-androstanediol, androstenedione, androstanedione and androsterone was achieved. The identities of the radiolabeled T metabolites were confirmed by recrystallization to constant specific activity. The results of the present study revealed that tissue recombinants expressed testosterone metabolic profiles only partially toward that of the adult prostate. For example, percentage formation of 5 alpha androstanedione, 3 alpha-androstanediol and unknown polar metabolites in the UGM + BLE resembled the prostate and differed significantly from the urinary bladder. Conversely, formation of the 3 beta-androstanediol and androsterone from testosterone resembled the urinary bladder and differed from the formation of these metabolites in the prostate. These results suggest that in contrast to histomorphology, androgen-induced DNA synthesis, androgen receptor binding activity and total tissue two-dimensional gel electrophoretic protein profiles, androgen metabolic profiles in the tissue recombinants showed only partial transformation into prostatic phenotypes. Analysis of steroid-metabolic profiles, therefore, may represent an exquisite and sensitive method to assess gene expression in various hormone-responsive target tissues. PMID- 4021497 TI - A simple technique to simultaneously assess activity at histamine H1- and H2 receptors in vivo. AB - A technique is described that allows simultaneous and quantitative assay of the action of agonists and antagonists at histamine H1- and H2-receptors in anesthetized guinea pigs. The principle of the technique is based on H1-receptor bronchoconstriction and H2-receptor tachycardia. Studies have been made to assay antagonists at either receptor and provide simultaneous evidence of selectivity or to assay combined antagonists such as Smith Kline & French 93319. Studies with histamine receptor agonists provide evidence of the potency and selectivity of these compounds relative to histamine. PMID- 4021498 TI - A rapid method for the determination of blood morphine concentration suitable for use in studies involving acute and chronic pain. AB - This communication provides an improved sample preparation method for blood morphine concentration determination prior to high-performance liquid chromatography analysis with electrochemical detection. The lower limit of sensitivity is 1 ng/ml of whole blood, and the standard curve is linear to an upper limit of 500 ng/ml. The coefficient of variation of replicate determinations of morphine at concentrations of 10 and 400 ng/ml were 4.7 and 2.5%, respectively. This assay procedure is rapid and accurate and allows the large number of samples (usually 30-40 samples) generated by pharmacokinetic studies in acute and chronic pain to be conveniently analyzed in one day. PMID- 4021499 TI - Differential intraarterial pressure recordings from different arteries in the rat. AB - Intraarterial pressures were recorded from five different sites in pentobarbital anesthetized rats. Simultaneous recordings were made from the brachial artery, carotid artery, femoral artery, tail artery, and a small end-branch of the superior mesenteric artery under basal conditions and under vasoconstrictor and vasodilator influences to find out whether similar mean arterial pressures (MAP) can be recorded from the various sites. It was found that MAP of proximal arteries (brachial and carotid) is higher than the MAP recorded from more distal arteries (mesenteric, tail, and femoral). A pressure difference of 5-6 mm Hg was found to exist from the level of the carotid artery to that of the femoral artery during all experimental conditions. Our results indicate that the same artery should always be used to compare MAP between different rats. Moreover, calculations of arterial resistance (MAP/BF) of most vascular beds in the rat, using MAP values obtained from the tail or the femoral artery, as are commonly done in physiologic or pharmacologic studies, can result in slightly lower resistance values than the true resistance. To obtain true arterial resistance of any vascular bed, one has to use MAP recorded at the particular vascular bed for the calculation of resistance. PMID- 4021500 TI - Measurement of adenosine metabolites and metabolism in isolated tissue preparations. AB - Several pitfalls have been encountered in setting up methodology for the study of adenosine metabolism and quantitation of adenosine metabolites in isolated tissue preparations. Quantitation of metabolites by high-performance liquid chromatography (HPLC) methods has shown that: 1. significant absorbtion of purines to some types of thread (used to tie up tissues in tissue baths) occurs; 2. without particular care in the preparation of tissue baths and medium, significant microbiological contamination can occur; 3. stimulation of guinea pig ileum preparations at 0.2 Hz is associated with weight loss of the tissue and release of purine-degrading enzymes into the bathing medium; 4. stability of purine analogs is dependent on the tissue and species. A method for the measurement of the purines uric acid, xanthine, hypoxanthine, inosine, adenosine, adenine nucleotides, and various substituted nucleotides in medium and tissue samples following incubations of rat vas deferens and guinea pig ileum is presented. PMID- 4021501 TI - Substrate aggregation and cooperative enzyme kinetics: consideration of enzyme access with large aggregates. AB - Consideration was given to a system in which an enzyme substrate indefinitely self-associates according to a general model with f sites of aggregation and a single intrinsic binding constant k. Where enzyme attack occurs at random points on the substrate surface, surface regions will be obscured from enzyme access by aggregate formation. The significance of reduced surface access for the infinite array of different size aggregates which co-exist was explored through use of a reacted site probability function, PA: the proportion of total substrate surface which is accessible to the enzyme was estimated as the fraction of total sites for aggregation which are unoccupied. The effective substrate concentration was thereby specified in terms of total substrate concentration (mA) by the simple expression mA = (1 - PA)mA. Plots of simulated v versus mA data were examined for a Michaelis-Menten enzyme of maximal velocity Vm and Michaelis constant Km to reveal deviations from expected enzyme behaviour; corresponding Hofstee (v/mA versus v) plots were found to be convex to the v axis as is characteristic of a negatively cooperative enzyme. As self-association is known to occur widely with large or small molecules in solution, the experimenter should be aware of the potential for these phenomena in kinetic studies to produce pseudo-allosteric effects, or to mask true allosteric behaviour. PMID- 4021502 TI - Experimental foundation of the Gabor-Nelson theory applied to boundaries which are non-insulating. AB - In order to found the application of the Gabor-Nelson theory to non-insulating boundaries, we have used a network which we have divided into two parts: a core energized by a source sink pair and an appendage, the conductivity of which may or may not differ from that of the core. By ignoring the appendage and by applying the Gabor-Nelson method to the restricted perimeter as if it were totally insulating, we stress the errors made in computing the dipole strength, orientation and position and how they are influenced by the dipole eccentricity, by its orientation with respect to the junction between the added portion and the core, and by a change in conductivity between the same compartments. Finally, we restore the dipole characteristics by using the appropriate correction derived from theory. Comparing the later results to those obtained by applying the Gabor Nelson method to the whole insulating boundary leads to the conclusion that the correction is founded and must be taken into account. PMID- 4021503 TI - The expected effect of a combination of agents: the general solution. AB - Interactions between agents (drugs, carcinogens, physiological stimuli, environmental pollutants, etc.) in producing their effects are of fundamental interest and practical importance in virtually every branch of biology and medicine. A combination of agents is said to show interaction when the magnitude of its effect is greater or smaller than expected, expectation being based on the dose-effect relations of the individual agents in the combination. The crux of the matter is to decide what is expected, and various rules have been proposed to this end (for example, that the expected effect is the sum of the effects of the individual constituents of the combination, or that it is the product of these effects, or that it may be calculated from the law of mass action). These rules are valid for combinations of agents with particular and rather restricted types of dose-effect relations, but they have no general validity. A general solution to this problem is given here, that enables the effects of non-interactive combinations to be calculated directly from the dose-effect relations of the individual agents (whether expressed algebraically or numerically), regardless of the particular types of dose-effect relations involved. This solution is based on the fact that, when an effect of particular magnitude is produced by a combination of n agents which do not interact to produce that effect, the point representing the combination in the n-dimensional space spanned by the dose-axes of the individual agents lies in the same (n-1)-dimensional hyperplane as those representing other combinations iso-effective with it and iso-effective amounts of the individual agents. Methods for calculating the effect of a non-interactive combination as the sum or product of the effects of its constituents, or from the law of mass action, each of which is correct in appropriate cases, may be deduced (without invoking mechanisms of action) by applying this general principle to particular types of dose-effect relations. PMID- 4021504 TI - Some problems in the usage of Gibbs free energy in biochemistry. AB - The usage of Gibbs free energy (G) in biochemistry is examined critically. The textbook formulation of the Second Law of Thermodynamics as applied to chemically reacting systems is reviewed. Cognizance of the established theory and terminology of chemical thermodynamics leads to the conclusion that the symbol "delta G", as used in most biochemical calculations of free-energy change (e.g. in freeze-clamp study of steady-state metabolic processes), is erroneous. The instantaneous change, symbolized by the expression (delta G/delta xi) (with xi the degree of advancement of the reaction), is seen to be the correct form for describing the thermodynamic quality of the reactions of cell metabolism. Mathematical and graphical analysis of a sample reaction demonstrates the fundamental difference between delta G and (delta G/delta xi). Some problems in the application and interpretation of free-energy change in biochemical systems are reviewed: (1) Advances in protein dynamics have revealed the free-energy linkage properties of the enzyme molecule in binding/catalytic events of catalysis, demanding that we view the thermodynamics of elementary enzyme reactions with a finer eye. (2) The reality of metabolic microenvironments in vivo leads to equivocation in the significance of free-energy changes measured under macroscopic conditions in vitro. (3) The physicochemical character of reaction dynamics in the living cell may in some cases exceed the domain of validity of such thermodynamic state functions as Gibbs free energy. PMID- 4021505 TI - Sex ratio, dominance status and maternal hormone levels at the time of conception. AB - Sex ratio is a topic which has attracted the attention of epidemiologists and evolutionary biologists. But their work has been conducted largely in parallel: hitherto they seem not to have found much inspiration in one another's results. Their attitudes, environments and problems have all been strikingly different. The present note shows how one of the biologists' findings may be explained by a hypothesis based on epidemiological observation. The hypothesis (that sex ratio of offspring is partially controlled by maternal hormone levels at the time of conception) needs testing in a number of species. PMID- 4021506 TI - Subjective antedating of a sensory experience and mind-brain theories: reply to Honderich (1984). AB - Honderich claims that our "delay-and-antedating" hypothesis, of a delay in cerebral production combined with a subjective antedating of a conscious sensory experience, involves self-contradiction which may cast doubt on some of our experimental findings and on the hypothesis. This claim misses the distinction between the phenomenological subjective mental content of an experience and the physical-neuronal configuration that elicits the experience; also, it cannot explain the experimentally observed discrepancy, between subjective timing and the empirically delayed time for cerebral adequacy for eliciting the experience, found when stimulating a subcortical sensory pathway. Honderich usefully distinguishes between our stated (delay-and-antedating) hypothesis and a different though unacceptable one which would have serious implications for mind brain theories. The delay-and-antedating hypothesis does not provide a formally definitive contradiction of monist-identity theory (of the mind-brain relationship). However, our experimentally based hypothesis does dissociate subjective/mental timing from the actual physical/neuronal time of an experience. This phenomenon, though conceptually strange, must be encompassed by any mind brain theory. PMID- 4021507 TI - Morphogen prepatterns during mitosis and cytokinesis in flattened cells: three dimensional Turing structures of reaction-diffusion systems in cylindrical coordinates. AB - Computer simulation of spontaneous morphogen prepattern formation (spatial dissipative structures, Turing structures) is studied during change from a spherical geometry to a flat cylinder (axis ratio 1:5), resembling compression of a spherical cell in metaphase to a flat disc. Abnormal forms of mitosis and cytokinesis have been reported experimentally during this process. The prepatterns obtained numerically account for several of these abnormalities, notably the occurrence of quadripartition in bipolar cells, or the arrest of cytokinesis. The prepatterns recorded may open a route for experimental testing of the prepattern model of mitosis and cytokinesis. PMID- 4021508 TI - Cell cycles and growth laws: the CCC model. AB - In the cell-cycle-with-control model (CCC model), cells have to satisfy a condition before they are allowed to pass a control point during G1. Different cycle durations within a cell population are explained by individual time spans needed to satisfy the passing condition. If the distribution of cycle durations is time invariant, the population will grow exponentially. However, if the average cycle duration becomes longer, while the population grows, non exponential population growth results. Simple functions for the lengthening of the average cycle duration, like linear or exponential ones, yield the well-known growth laws found in the biological literature. The same functions can be represented by an "S-system" differential equation that was derived earlier as an approximation for biochemical systems with many fast reactions (metabolism) and one slow process (e.g. ageing). PMID- 4021509 TI - The relationship between zeros and factors of binding polynomials and cooperativity in protein-ligand binding. AB - Cooperativity in the protein-ligand binding process is discussed in terms of the zeros of the binding polynomial and the corresponding possible factorizations of the binding polynomial into polynomials having non-negative coefficients. Particular attention is paid to the case in which the real parts of all zeros are negative (Hurwitz polynomial) and the case in which the binding polynomial admits no positive factorization (positive irreducible polynomial). Such factorizations are then interpreted as site linkage patterns and related to cooperativity. The possible combinations of zeros of the binding polynomials for the MWC and KNF tetrahedral, square and linear models are determined and the corresponding factorization and linkage patterns analyzed. An application and interpretation are then made for data obtained from Trout I hemoglobin. PMID- 4021510 TI - A theoretical model for calcium absorption from the intestinal lumen. AB - A theoretical model is developed for the absorption of calcium in the human gut and a mathematical description of the model is written. For simplicity, only three compartments are considered to derive a kinetic equation which can be fit to plasma activity measurements following oral ingestion of radiotracer calcium. Initial tests show good success in correlating total fractional absorption of calcium. PMID- 4021511 TI - Preliminary study of ethnobotany in Xishuang Banna, People's Republic of China. AB - Xishuang Banna, a particularly rich area for ethnobotanical research, borders on Burma and Laos, and contains some of the last undisturbed tropical rainforests in China. Xishuang Banna is ethnically very diverse; the largest group is the Dai followed by the Hani (Aini) and various smaller national minorities. Since the various groups inhabit different parts of the environment (from river valleys to steep mountain slopes) their awareness of, and use of plants varies considerably. The Dai people for example, have a tradition of forest preserves for each village as well as family home gardens around each house. This study lists 218 plant species that are frequently used by the various nationalities included in the survey. PMID- 4021512 TI - Screening of medicinal plants used by Huastec Mayans of northeastern Mexico. AB - As part of a research effort to assess the adaptive value of Huastec medicine, a preliminary screening of a sample of the Huastec pharmacopoeia has been carried out. Results from the screening of 56 species are reported here together with information about Huastec use and knowledge of medicinal plants. PMID- 4021513 TI - Experimental anti-ulcer activity of Veronica officinalis L. extracts. AB - In indomethacin-induced ulcers in albino rats, the anti-ulcerogenic effects of some extracts prepared from Veronica officinalis L. were investigated. The extracts had a significant anti-ulcerogenic activity. In ulcer healing experiments performed in rats by administering reserpine, the extracts were found to enhance the regeneration of the gastric mucosa. These results seem to confirm the popular observations according to which the decoction from Veronica officinalis L. possessed useful properties in the treatment of gastric ulcers. PMID- 4021514 TI - Muscle relaxant activity and hypotensive activity of some Tabernaemontana alkaloids. AB - Stemmadenine, the major alkaloid from the seeds of Tabernaemontana dichotoma, showed hypotensive activity and weak muscle relaxant activity. Perivine, vobasine, coronaridine and dichomine, some of the alkaloids found in the leaves, fruits and bark of T. dichotoma, also showed hypotensive and muscle relaxant activity. PMID- 4021515 TI - Pharmacology of ephedroxanes. AB - On the central nervous system, ephedrine showed intense stimulatory activities but pseudoephedrine mediated weaker influences, while ephedroxane and pseudoephedroxane exerted inhibitory actions. The effects of ephedroxane were generally intense as compared with those of pseudoephedroxane. On the autonomic nervous system, the ephedrines contracted vas deferens and potentiated the effect of norepinephrine, while the ephedroxanes elicited no contraction of vas deferens but potentiation of the action of norepinephrine in the catecholaminergic nervous system. In antihistamine and antibarium activity, the ephedrines elicited remarkable actions but the effects of the ephedroxanes were weak. PMID- 4021516 TI - A drug used in traditional medicine: Harpagophytum procumbens DC. III. Effects on hyperkinetic ventricular arrhythmias by reperfusion. AB - In Langendorff preparations of rat heart, hyperkinetic ventricular arrhythmias (HVA) have been induced by an ischaemic perfusion (coronary flux 0.5 ml/min; pressure 8 mmHg) and following reperfusion at basal conditions (coronary flux 8 ml/min; pressure 50 mmHg). Crude methanolic extracts of Harpagophytum procumbens secondary roots and harpagoside showed a significant, dose-dependent, protective action toward HVA induced by reperfusion. PMID- 4021517 TI - A drug used in traditional medicine: Harpagophytum procumbens DC. IV. Effects on some isolated muscle preparations. AB - Effects of the crude methanolic extract of Harpagophytum procumbens secondary roots and two of its active principles, harpagoside and harpagide, on some smooth muscle in vitro have been studied. The results obtained show how the action of H. procumbens is due to a complex interaction between the various active principles contained in the drug and suggest that they, especially harpagoside, interfere with the mechanisms that regulate the influx of calcium in the cells. PMID- 4021518 TI - Screening of medicinal plants of Rwanda for acaricidal activity. AB - A series of 108 samples from 42 medicinal plants of Rwanda have been screened for acaricidal activity against the female tick Rhipicephalus appendiculatus. Two plants, Solanum dasyphyllum (fruits) and Neorautanenia mitis (roots) showed apparent acaricidal activity in the petroleum ether fraction. PMID- 4021519 TI - Cholagogic effect of ginger and its active constituents. AB - The effect of bile secretion in rats was examined in order to clarify the stomachic action of ginger and also to investigate its active constituents. The results showed that mainly the acetone extracts of ginger, which contain essential oils and pungent principles, caused an increase in the bile secretion. Further analyses for the active constituents of the acetone extracts through column chromatography indicated that [6]-gingerol and [10]-gingerol, which are the pungent principles, are mainly responsible for the cholagogic effect of ginger. PMID- 4021520 TI - Mangiferin from the root bark of Salacia reticulata. PMID- 4021521 TI - Surgical treatment of chronic empyema. A new one-stage operation. AB - The operative results in a series of 92 patients with chronic empyema were reviewed. Of these, 46 had empyema with an underlying fistula, and 46 had empyema without fistulization. Twenty-one underwent decortication, 65 were treated by our technique, and six were treated by a modification of the Eloesser technique. These techniques were employed with priority given in the order just cited. Our technique involves decortication of the visceral peel and obliteration of the dead space by collapsing of the parietal wall without rib resection. Cure was obtained with decortication alone in 20 of 21 patients. Sixty of 65 patients treated by our technique were cured without deformation of the thoracic cage. In all patients treated by the modified Eloesser technique, obliteration of the empyema cavity was achieved secondarily by thoracoplasty combined with a pedicled muscle flap. Postoperative pulmonary function studies demonstrated a significant improvement in vital capacity and forced expiratory volume in 1 second in patients treated by decortication or by our technique. With the modified Eloesser technique, in contract, pulmonary function tended to decline. PMID- 4021522 TI - Giant lung abscess treated by tube thoracostomy. AB - Pulmonary resection is the recommended treatment for large lung abscesses that do not respond to medical management. Tube thoracostomy, effective in the past, has been used less and less in recent years. Personal experience with three patients and a review of the literature led me to the following conclusions: In the treatment of a lung abscess 8 cm or larger, tube thoracostomy is an effective form of drainage, is probably safer than pulmonary resection, and may yield a superior result. Rather than being reserved as a desperation measure for poor risk patients, tube thoracostomy should be considered early in the hospital course. PMID- 4021523 TI - Cryosurgical ablation of left parietal wall accessory atrioventricular connections through the coronary sinus without the use of extracorporeal circulation. AB - A simplified technique for surgical treatment of preexcitation syndrome caused by left-sided accessory atrioventricular connections without the use of extracorporeal circulation has been elaborated experimentally and used in 21 patients with tachycardia refractory to medical treatment. Cryoablation of the accessory bundles was performed by means of local cryothermia using a specially designed cryoinstrument introduced into the coronary sinus through the right atrial wall. The operations were performed after thoracotomy on the working closed heart. The signs of preexcitation and paroxysms of tachycardia disappeared in 19 of 21 patients. Coronary sinus ligation was necessary in two patients. In the rest of the patients the patency of the sinus was preserved and there were no surgical complications. This original cryosurgical technique offers a number of advantages in selected patients with Wolff-Parkinson-White syndrome. PMID- 4021524 TI - Cryosurgical ablation of right parietal and septal accessory atrioventricular connections without the use of extracorporeal circulation. A new surgical technique. AB - A new technique for definitive surgical treatment of the preexcitation syndrome without the use of extracorporeal circulation has been elaborated and clinically used in 25 patients with Wolff-Parkinson-White syndrome. Seventeen patients had right parietal accessory atrioventricular connections and eight had septal connections. In patients with right-sided connections the fat pad in the coronary sulcus was dissected with an ultrasonic scalpel. Ablation of accessory atrioventricular connections was obtained by applying local cryothermia. The evidence of preexcitation and arrhythmias disappeared in all patients. All patients recovered without surgical complications and there were no deaths. The described technique offers considerable advantages over previous surgical methods in selected patients with Wolff-Parkinson-White syndrome. PMID- 4021525 TI - Imidazole-buffered cardioplegic solution. Improved myocardial preservation during global ischemia. AB - Progressive acidosis is a constant finding in global myocardial ischemia and is associated with reduced myocardial contractility after ischemia. The hypothesis tested in these experiments was that imidazole (pKa = 6.7 at 37 degrees C), a commonly used buffer in physiology and microbiology, would provide superior buffering capacity when used in lieu of bicarbonate (pKa = 6.1 at 37 degrees C) in a cardioplegic solution. Twenty-eight isolated, working rabbit hearts were perfused, and preischemic and postischemic determinants of performance were measured. The 30 minute interval of normothermic global ischemia was altered by the injection at 0 and 15 minutes of 2 ml/gm wet weight of a buffered cardioplegic solution. Control hearts received a bicarbonate-buffered cardioplegic solution and experimental hearts received a solution buffered with imidazole. In the imidazole-buffered group, there was a superior recovery of coronary flow, developed left ventricular pressure, peak rate of rise of left ventricular pressure, peak rate of relaxation, and stroke work indices (p less than 0.05). Recovery of mechanical parameters was coincident with an improved acid-base status of the coronary sinus effluent at the end of ischemia. Coronary sinus effluents in the imidazole group had significantly higher pH values and lower partial pressures of carbon dioxide than coronary sinus effluents in the bicarbonate-buffered group (p less than 0.001). The data suggest that improved buffering of the extracellular and possibly intracellular space during global ischemia with a nonbicarbonate buffer is beneficial and provides improved postischemic myocardial recovery. PMID- 4021527 TI - Experimental use of intercostal muscle flaps for repair of induced cardiac defects. AB - Intercostal muscle flaps were successfully used to repair 3 cm defects of the ventricular myocardium in the mongrel dog. Early and late healing of all flaps was uncomplicated and there were no late complications related to aneurysmal formation or electrical abnormalities of the heart. The existing blood supply of the heart was unaffected. The intercostal muscle is suggested as an alternative muscle flap for use in myocardial wall reconstruction. PMID- 4021526 TI - Noninvasive assessment of exercise cardiac function before and after pectus excavatum repair. AB - Surgical correction of pectus excavatum frequently results in subjective improvement of exercise tolerance. Whether or not cardiac function improves after repair remains controversial and has primarily been limited to isolated case reports. The purpose of this investigation was to assess changes in cardiac function during rest and exercise associated with the surgical correction of this deformity. First-pass radionuclide studies during upright rest and bicycle exercise were performed on 13 patients before and at least 6 months after pectus excavatum repair. Operation did not change left ventricular ejection fraction or cardiac index at rest or during exercise. However, the left ventricular end diastolic volume index and stroke volume index increased at rest after surgical correction. The estimated resting right ventricular end-diastolic volume also increased markedly after operation and was associated with a decrease in right ventricular ejection fraction. These data show no limitation in exercise cardiac function that could be relieved by pectus repair. However, the increase in right and left ventricular volume after operation suggests that some cardiac compression is relieved by operative repair. PMID- 4021528 TI - Incidence of primary tissue valve failure with the Ionescu-Shiley pericardial valve. Preliminary results. AB - This report provides retrospective follow-up data on 88 patients who received an Ionescu-Shiley bovine pericardial valve in the aortic position between August, 1977, and June. 1980. Seven instances of primary tissue degeneration occurred in seven of the 65 patients followed up until June, 1984. Cumulative duration of follow-up was 335.5 patient-years. The linearized incidence of primary tissue failure was 2.08% per patient-year. The actuarial rate of freedom from valve failure for patients with an Ionescu-Shiley valve in aortic position was 79% +/- 8% at 7 years of follow-up. This series shows a higher incidence of primary tissue failure with this prosthesis than with the glutaraldehyde-preserved porcine xenograft in the aortic position at 7 years' follow-up. PMID- 4021529 TI - Pericardial meshing: an effective method for prevention of pericardial adhesions and epicardial reaction after cardiac operations. AB - Cardiac reoperations, particularly for coronary revascularization, are becoming more frequent and carry increased risk of damage to the heart during resternotomy. We experimentally evaluated a pericardial meshing technique to facilitate primary pericardial closure. In 18 mongrel dogs, an 8 by 5 cm pericardial flap was fashioned through a left thoracotomy. A standardized procedure for induction of pericardial adhesions was carried out in all animals. Animals were divided into three groups of six animals each: Group I (control)- the pericardial flap was primarily resutured; Group II--the flap was meshed and then resutured; and Group III--the flap was replaced by a pericardial substitute. Animals were put to death 8 weeks postoperatively and the pericardial space was examined for adhesions and epicardial reaction. The extent of adhesions and epicardial reaction was graded as: 0--none; 1--minimal; 2--moderate; and 3- severe. Both in Group I and Group III severe pericardial adhesions (grade 2-3) and epicardial reactions (grade 2-3) were formed, which obscured the underlying coronary anatomy. In Group II pericardial adhesions and epicardial reactions were none to minimal (grade 0-1) and the underlying coronary anatomy was not obscured. The meshed pericardium was completely regenerated by normal pericardium within several weeks. This study demonstrates that pericardial meshing facilitates primary tension-free pericardial closure. Free drainage of intrapericardial blood is achieved. A complete anatomic layer between heart and sternum is restored. Pericardial meshing is superior to the pericardial substitutes examined, as adhesions and epicardial reactions are significantly reduced, and the coronary anatomy is readily identifiable. PMID- 4021530 TI - Pathophysiology of chronic cyanosis in a canine model. Functional and metabolic response to global ischemia. AB - To investigate the pathophysiology of chronic cyanosis, we subjected 14 adult mongrel dogs to diversion of the inferior vena cava to the right inferior pulmonary vein. This produced a mean oxygen tension of 42 +/- 2 mm Hg and a calculated right-to-left shunt of 52.0% +/- 3.9%. These animals (Group C) and 15 normal dogs (Group N) were subjected to cardiopulmonary bypass with 20 minutes of normothermic global ischemia. Functional indices studied were rate of rise of left ventricular pressure and the end-systolic pressure/volume ratio. Metabolic status was assessed by obtaining transmural myocardial biopsy specimens for measurement of adenosine triphosphate content. Myocardial blood flow was measured with radiolabeled microspheres. There were no significant differences between Group C and Group N in either functional index or blood flow measurement prior to global ischemia. At 45 minutes after ischemia, Group N animals had a significantly greater rate of rise of left ventricular pressure (at a left ventricular end-diastolic pressure of 0, 5, 10, and 15 mm Hg, p less than 0.025 to 0.05) and subendocarial perfusion (endocardial/epicardial flow ratio 0.961 +/- 0.037 versus 0.815 +/- 0.021, p less than 0.01). At 90 minutes after ischemia, Group N animals exhibited a significantly higher end-systolic pressure/volume ratio (4.9 +/- 0.7 versus 3.0 +/- 0.4 mm Hg/ml, p less than 0.05), rate of rise of left ventricular pressure (at an end-diastolic pressure of 0 to 20 mm Hg, p less than 0.005 to 0.05), and endocardial/epicardial flow ratio (1.065 +/- 0.046 versus 0.829 +/- 0.059, p less than 0.01). No differences in adenosine triphosphate content were found at any sampling period. The Group C left ventricles exhibited no hypertrophy but were significantly dilated compared to Group N (38.8 +/- 0.3 versus 30.1 +/- 0.2 mm, p less than 0.05). Inferior vena cava to pulmonary vein diversion produces cyanosis with left ventricular dilatation but without hypertrophy. It is proposed that abnormal loading characteristics of the left ventricle are responsible for the functional derangements that result from global ischemia. PMID- 4021531 TI - The landmarks to the atrioventricular conduction system in hearts with absence or unroofing of the coronary sinus. AB - Histologic studies were made of the conduction system of two hearts, one with absence and the other unroofing of the coronary sinus. The findings show that, when present, the triangle of Koch and the orifice of the coronary sinus are usually good guides to the atrioventricular conduction axis. However, when these landmarks are malformed, or there is malalignment of the atrial and ventricular septal structures, a better guide is the fusion point of the ventricular septum with the atrioventricular junction. PMID- 4021532 TI - Multiple-vessel coronary revascularization with combined in situ and free sequential internal mammary arteries. AB - Bilateral internal mammary arteries were used sequentially (one as an in situ graft to provide inflow and the other as a free graft to provide outflow) in a patient with multiple-vessel coronary artery disease requiring revascularization without an autologous venous conduit available. PMID- 4021533 TI - Repair of complex subvalvular aortic aneurysm with a valved conduit. AB - A subaortic annular aneurysm involving three fourths of the annular circumference was repaired with a valved conduit to which a Teflon felt flange was attached. This unique prosthetic repair assured a strong stable repair and uncompromised coronary flow otherwise unobtainable with previously described repairs. PMID- 4021535 TI - Bypass grafting in patients with renal failure. PMID- 4021534 TI - Thymolipoma in association with Hodgkin's disease. AB - Thymolipomas are rare mediastinal tumors. They have been described with a variety of systemic diseases. To our knowledge they have never been described in association with Hodgkin's disease. The significance of this association is unknown. PMID- 4021537 TI - Management of caval obstruction from pericardial baffles. PMID- 4021536 TI - Packaging of a 25 mm synthetic aortic prosthesis as a 23 mm valve. PMID- 4021538 TI - Intraoperative assessment of the reconstructed mitral valve. PMID- 4021539 TI - Cardiovascular effects of protamine sulfate. PMID- 4021540 TI - Simultaneous development of humoral and cellular tumor-specific immunity against L1210 mouse leukemia. AB - We have recently described that a variant of L1210 leukemia cell (L1210/LN-1) originally fused with Lesch-Nyhan fibroblast is highly immunogenic for inducing tumor-specific transplantation immunity in (BALB/cxDBA/2)F1 mice. This finding has clearly been confirmed in the present study by in-vitro cell-mediated cytotoxicity assay. Direct cytotoxic tests and competitive inhibition tests using tumor cells such as P388, LS-1 and L5178Y as target or inhibitor cells showed that the cell-mediated immunity is specific to L1210 leukemia. In the process of this study, we found that the CD2F1 mice hyperimmune to L1210 leukemia cells developed co-existing humoral anti-L1210 leukemia immunity. In an in vitro complement-dependent cytotoxicity test and absorption test, antisera from hyperimmune mice reacted specifically to L1210 leukemia cells, but not other tumor cells such as P388, L5178Y, LS-1, DB27C and BW5147 or normal cells from various tissues of DBA/2, BALB/c and AKR mice. In an in vitro cytotoxicity blocking test, the cytotoxic antisera specifically reactive to L1210 cells totally failed to inhibit lysis of L1210 cells by cytotoxic cells, suggesting that antigens recognized by cell-mediated cytotoxicity assays are not identical to serologically defined tumor-cell surface antigens. PMID- 4021541 TI - Microbubble detection during cardiopulmonary bypass for open-heart surgery. PMID- 4021542 TI - Short papers from the XIth Congress of the European Society for Artificial Organs, September 1984. PMID- 4021543 TI - Haemodynamics during arterio-arterial extracorporeal circulation in the dog. PMID- 4021544 TI - Entamoeba polecki infection in Southeast Asian refugees: multiple cases of a rarely reported parasite. AB - Recently, Entamoeba polecki was identified for the first time in our parasitology laboratory in stool specimens from eight Southeast Asian refugees. This ameba has been reported infrequently in the Western world; most reported cases have been from the New Guinea region. In most previously described patients and in our patients, no definite gastrointestinal symptoms could be directly attributed to E. polecki infection. Morphologically, E. polecki may mimic the pathogen E. histolytica and also nonpathogens such as E. coli. These species are most readily distinguished by studying encysted forms. In contrast to E. histolytica and E. coli, E. polecki characteristically has uninucleate cysts. Both pigs and monkeys naturally harbor E. polecki, but four of the patients in this series had no apparent contact with these animals. Other modes of infection may be human-to human transmission or acquisition from other domestic animals. Six of our eight patients were treated successfully with one course of metronidazole in a regimen similar to that used for E. histolytica infection. In the two other patients, repeated courses of therapy eradicated the infection. Because of the recent increase in number of Southeast Asian immigrants to the United States, E. polecki may be identified more frequently than in the past. Physicians and laboratory personnel should be familiar with this organism, because it may be confused with E. histolytica or may act as a pathogen. PMID- 4021545 TI - Stroke after temporal artery biopsy. PMID- 4021546 TI - Cardiac sarcoidosis: a potentially treatable form of myocarditis. AB - A 39-year-old woman had a 2-year history of heart block, which had necessitated pacemaker implantation, and a 6-month history of heart failure. Endomyocardial biopsy specimens initially revealed lymphocytic myocarditis but subsequently showed giant cell myocarditis. She died suddenly, and autopsy disclosed extensive cardiac sarcoidosis with minimal extracardiac involvement. Cardiac sarcoidosis may be difficult to diagnose clinically because the extent of cardiac and the extent of extracardiac involvement tend to be inversely related. Endomyocardial biopsy may be helpful in diagnosing such cases. PMID- 4021547 TI - Chemical dependence among adolescents. PMID- 4021548 TI - Treatment of severe nephrotic syndrome with meclofenamate: an uncontrolled pilot study. AB - The effect of meclofenamate on urinary protein excretion, level of serum albumin, and renal function was studied prospectively in 30 patients with corticosteroid resistant severe nephrotic syndrome: 16 with focal segmental glomerulosclerosis, 12 with membranous glomerulopathy, and 2 with minimal-lesion nephropathy. Seventeen patients had a 40% or more reduction in urinary protein excretion ("responders"), and the decrease continued during long-term treatment. Meclofenamate therapy was discontinued after 2 months in eight "nonresponders" and in five other patients because of side effects (progressive increase in the level of serum creatinine in two, diarrhea in two, and pruritus in one). In responders, we recorded the following findings (mean +/- SD): urinary protein excretion decreased from 13.0 +/- 5.2 g/24 h to 7.2 +/- 3.5 g/24 h in 2 to 4 weeks and continued to decrease to 4.1 +/- 1.4 g/24 h at the time of the last follow-up study (median duration, 12 months; range, 6 to 36 months; P less than 0.01, 2 to 4 weeks versus later follow-up); the level of serum albumin increased from 1.9 +/- 0.5 g/dl to 2.9 +/- 0.7 g/dl (P less than 0.001) in 2 to 4 weeks; the level of serum cholesterol decreased from 413 +/- 125 mg/dl to 346 +/- 114 mg/dl (P less than 0.005) at the time of the last follow-up examination; and renal function remained unchanged from the baseline study to the follow-up study (serum creatinine 1.5 +/- 0.5 mg/dl versus 1.6 +/- 0.4 mg/dl and glomerular filtration rate 60.5 +/- 29.2 ml/min per 1.7 m2 versus 64.1 +/- 25.5 ml/min per 1.7 m2).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4021549 TI - A rapid, sensitive assay for analyzing defects in metabolism of steroids in normal and diseased human tissues. AB - In this report, we describe a simple, rapid biopsy-steroid metabolism assay that is applicable to any steroid tissue system. It consists of mincing the sample, tissue culture incubation, extraction of the steroids and their metabolites from the tissue, and fractionation of the metabolites by high-pressure liquid chromatography (HPLC). Radioimmunoassay is used to verify the elution patterns of certain steroids. Studies of the metabolism of [3H]progesterone in the avian oviduct showed the generation of metabolites that eluted from the HPLC system in a pattern similar to androgens, estrogens, and glucocorticoids. Studies of the metabolism of [3H]testosterone in the human foreskin showed the production of metabolites that eluted from the HPLC system similar to 5 alpha dihydrotestosterone and 5 alpha-androstane-3,17-dione (androstanedione) from the parent [3H]testosterone. In the production of the metabolite that eluted as androstanedione in samples of foreskin from normal subjects, a significant (P less than 0.001) correlation was found with the age of the donor. Preliminary studies of patients with hypospadias showed a significant (P less than 0.005) decrease in the production of "androstanedione" compared with that in normal subjects. Because of the wide range in rates of metabolism of testosterone in the patients with hypospadias, the effect of age does not seem to be the sole determinant of a low rate of metabolism in these patients. Some samples of hypospadias foreskin had a decreased rate of production of a metabolite that eluted as dihydrotestosterone in comparison with normal foreskin, even when the age of the donor was considered. The assay described herein should be applicable to any surgical biopsy specimen and to all steroids.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4021550 TI - Amiodarone pulmonary toxicity: report of two cases associated with rapidly progressive fatal adult respiratory distress syndrome after pulmonary angiography. AB - Use of amiodarone, an investigational antidysrhythmic agent, has been associated with cases of pulmonary toxicity. The mechanism of amiodarone pulmonary toxicity is unknown, and recommendations for the assessment and treatment of patients with this condition continue to evolve. In two patients with clinically diagnosed amiodarone pulmonary toxicity, a rapidly progressive and fatal adult respiratory distress syndrome developed after pulmonary angiography. Physicians should be aware of the potential for serious complications of pulmonary angiography in patients with presumed or clinically diagnosed amiodarone toxicity. PMID- 4021552 TI - Selection and training of physicians at Mayo Medical School for the 21st century. PMID- 4021551 TI - Effect of resection of the sternum and manubrium in conjunction with muscle transposition on pulmonary function. AB - We recorded the changes in pulmonary function that occurred after removal of the sternum and manubrium and repair by pectoralis major muscle transposition in six patients. Of these patients, three had osteomyelitis of the manubrium and sternum, two had osteosarcoma of the sternum, and one had osteomyelitis and radionecrosis of the manubrium and sternum. Body plethysmography and the rebreathing, hypercapnic ventilatory response test with inductive plethysmographic recordings of chest-wall motion were performed preoperatively and postoperatively. Preoperatively, four of the six patients had evidence of mild to moderate chest-wall restriction. Pulmonary function was normal in the other two patients. Postoperatively, total lung capacity was unchanged but the vital capacity decreased 11.5% in the overall group. Static compliance, retractive force, and the steady-state diffusing capacity for carbon monoxide decreased modestly but significantly postoperatively. The expiratory flow rates and maximal voluntary ventilation remained unchanged. Preoperatively, the slope of the hypercapnic ventilatory response was less than that predicted. Postoperatively, the slope did not change. In three patients, however, increased dependence on the abdomen for breathing suggested a dynamic restriction of rib cage motion. On the basis of our findings, we conclude that surgical removal of the sternum and manubrium in conjunction with muscle flap repair is a well tolerated procedure. Any postoperative changes in pulmonary function are minor. PMID- 4021553 TI - Relationship of body temperature stability to mortality in aging mice. AB - An age-related decline in the capacity for thermoregulation among homeothermic animals has been observed frequently under conditions of extreme ambient temperatures. We investigated the temporal stability of the internal body temperature of 69 C57BL/6J mice from 25 months of age until death in a controlled, neutral thermal environment. Estimates of temporal variability were calculated over consecutive 1-month intervals using (colonic) body temperature data collected weekly. The results of this longitudinal analysis indicated that the regulation of body temperature, as measured by its temporal stability, became increasingly less precise with advancing age. Body temperature exhibited a significant decline as the animal approached death. Individual differences in body temperature and the temporal regulation of body temperature were significantly correlated with lifespan, although the direction of the relations were opposite. Body temperature correlated positively with lifespan, whereas the temporal stability of body temperature correlated negatively with lifespan. Thus, animals exhibiting higher body temperatures and greater temporal stability also tended to live longer than their cohorts. PMID- 4021554 TI - Effect of lead on fibroblasts taken from an 84-year-old donor. AB - Human, diploid fibroblasts from an 84-year-old donor (AlPos) were used to study the effect of 20, 40 and 80 micrograms/100 ml concentrations of lead on in vitro senescence. The results showed that there was a significant decrease in the number of total population doublings due to the treatment with lead. However, there was no significant difference between the effects of the three concentrations of lead. As far as nucleolar number is concerned in the case of the controls as well as in the lead-treated cells the number remained constant with aging in vitro. When the areas and dry mass of cells, nuclei and nucleoli were examined in controls and lead-treated groups at early and late doublings the results showed that in general no significant changes were noted with the exception of the 40 micrograms/100 ml lead treatment which caused a significant increase in these parameters with aging in vitro. The results are discussed and compared to those from a previous study [17] in which embryonic, IMR-90 cells were treated in a similar way. It is concluded that the fibroblasts from the 84 year-old donor AlPos are even more vulnerable than the embryonic cells to the effects of lead as indicated by the drastic curtailment of the in vitro lifespan exhibited in the case of treatment even with the lowest concentration of lead.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4021555 TI - Changes in endogenous DNA damage in aging mice in response to butylated hydroxyanisole and oltipraz. AB - The extent of DNA damage (single strand breaks) was measured in the livers of female Swiss-Webster mice up to 24 months of age. The effects of the antioxidants butylated hydroxyanisole (BHA) and oltipraz on this DNA damage were also measured. Oltipraz is an antioxidant which is structurally related to compounds found in cruciferous vegetables. From 6 months on the extent of DNA damage increased, reaching a maximum about 18 months old. Limited administration of both BHA and oltipraz to mice significantly reduced the levels of hepatic DNA damage. PMID- 4021556 TI - A mathematical analysis of aging influences on enzyme deactivation/activation kinetics. Examples of the influence of regional brain development and drugs in rats. AB - A series-type enzyme deactivation/activation model involving active enzyme states is utilized to theoretically quantify the influence of regional brain development and drugs on enzyme activity levels in rats. Continuous hexachlorobenzene administration with, or without, phenobarbitone pretreatment has different effects on the deactivation/activation kinetics of porphyrinogen carboxylase, delta-aminolaevulinate synthase and delta-aminolaevulinate dehydratase. The deactivation/activation kinetics exhibited by pyruvate dehydrogenase, citrate synthase, and D-3-hydroxybutyrate dehydrogenase during the development of the medulla oblongata, mid-brain, striatum, and hypothalamus sections exhibit similarities as well as discrepancies. These are identified and made more quantitative. PMID- 4021557 TI - Effect of thymus grafts of various ages on the immune system formation in CBA mice. AB - An attempt has been made to govern the development of immunological capability in CBA mice by means of transplantation at an early postnatal period of thymus from donors of various ages. The results have shown that in thymectomized animals, apart from a well known gradual decline with the donor's age in restorative functions of the transplanted thymus, there was at the age of 22 months a phase of inhibitory influence on the recipient's immune system. In intact animals, transplantation of the thymus from a 5-day-old donor caused a decrease and that from a 22-month-old donor caused an increase in the development of the capacity for immune response. Taken together, our findings indicate an active role of the thymus both in the formation of the immune system and in its alteration with aging. PMID- 4021558 TI - Food restriction, ionizing radiation, and natural selection. AB - It is proposed that the allocation of energy in the animal body is modulated automatically by the endocrine system which through one or more centers responds directly to the oxygen radical flux (or an appropriate surrogate) derived from the metabolism of the ingested food. It is also proposed that energy to maintain temperature as well as reproduction and the reproductive capacity are the main sources of oxygen radicals that may be the direct cause of aging. Energy used for gathering food, resisting predators, play (i.e., most voluntary muscle action), contributes little to aging. The diversion of energy from basal metabolism and reproduction to muscular work when demanded by reduced food supply should, therefore, lead to an increased lifespan potential and an increased variance in the lifespan of a population. The change in variance favors production of offspring with longer lifespans, lower reproductive and basal metabolic rates and larger size potential. The reverse process occurs when food becomes abundant. The introduction into the body of oxyradicals, as by whole body irradiation with X or gamma rays should, therefore, mimic the ingestion of extra food and result in similar changes. At low radiation exposures the results are seen as seemingly beneficial (hormetic) effects in animals. It is shown here that some human populations seem to show evidence of the described adaptation to differences in food supply. PMID- 4021560 TI - Programmed aging or error catastrophe? An examination by two-dimensional polyacrylamide gel electrophoresis. AB - We have examined newly synthesized proteins in the young adult and in older populations of the nematode Caenorhabditis elegans using two-dimensional polyacrylamide gel electrophoresis (2D PAGE). A temperature-sensitive mutant strain, DH26, with a mean life span of about 15 days, under our conditions, was used to block progeny development. Nematodes of several different ages were pulse labeled for 5 h, in vivo, with 35S-labeled E. coli, A subsequent 30-min chase with unlabeled E. coli served to rid the worms of endogenous labeled E. coli proteins. We resolve 700 or more proteins by 2D PAGE polyacrylamide gel electrophoresis of extracts of young nematodes. The patterns of these proteins are highly reproducible in comparisons of independent repeats of identical experiments. No new major proteins are synthesized at any time during the adult phase (4-22 days) nor are any of the most abundant proteins not made during this period. At our level of detectability (estimated as a satellite spot containing 4% of the amount of label in a major spot) we see no misincorporation of radioactive amino acids into newly synthesized proteins. These data are inconsistent with predictions by any one of several, so called, "error catastrophe" models of senescence and also show that modulation of the highest abundancy classes of proteins are also not involved in senescence. PMID- 4021559 TI - Membrane glycoprotein changes during the senescence of normal human diploid fibroblasts in culture. AB - The plasma membrane is intimately involved in a variety of cellular phenomena and may play an important role in the aging of human cells in culture. Significant differences in human diploid fibroblast surface glycoproteins were observed with in vitro aging. Senescent cells bound more concanavalin A (Con A) than young cells and exhibited two distinct classes of binding sites. Cell surfaces of senescent cells incorporated less labelled mannose and more labelled fucose and glucosamine than young cell surfaces. Membranes prepared from older cells were also less effective than membrane preparations from young cells in incorporating mannose from GDP-mannose into a group of oligolipid intermediates, required for the synthesis of glycoproteins with asparagine-linked oligosaccharides. These results demonstrate novel quantitative changes in membrane structure and lectin reactivity in aging human diploid fibroblasts, which must reflect the fundamental physiological modifications in the cell that occur during senescence. PMID- 4021561 TI - On the ontogeny of aldolase isozymes and their interactions with cellular structure. AB - In an endeavour to extend the available information on the biological significance of the interactions between aldolase and cellular ultrastructure, the extent of association has been studied in the tissues of the mouse during the major stages of development from embryo to adult. Analysis of the isozyme status in these compartments and the latency of the enzyme during tissue differentiation was also effected. In all tissues investigated, a considerable variation in the degree of association of aldolase with structure was evident during development. Binding was particularly extensive in the early embryonic stages, but regardless of the tissue or the stage of differentiation, binding preference was directed towards A-type activity over the B- and C-type of enzyme. Substantial latent activity of aldolase was evident only in brain in the postnatal stages of development, and not in the other tissues or early stages of ontogeny. The significance of these ontogenic phenomena have been discussed, along with the physiological variations in individual tissues during maturation. PMID- 4021562 TI - Evidence for age-dependent impairment of ovalbumin heterogeneous nuclear RNA (HnRNA) processing in hen oviduct. AB - The expression of the ovalbumin gene in hen oviduct decreases during ageing. Northern transfer of electrophoretically fractionated total RNA from oviducts of mature egg-laying and old non-egg-laying hens, and hybridization to nick translated plasmid pOV230 (ovalbumin complementary DNA cloned into pMB9) revealed with age increasing concentrations of distinct high-molecular-weight ovalbumin pre-mRNA species as compared with that of functional 18S ovalbumin mRNA. The accumulation of ovalbumin sequence-containing processing intermediates in old hen oviducts indicates lowered rates of RNA splicing and/or altered steady state concentrations of splicing intermediates during post-transcriptional maturation of heterogeneous nuclear RNA in old animals. PMID- 4021563 TI - Continuous measurement of aortic radius change in vivo with an intra-aortic ultrasonic catheter. PMID- 4021564 TI - Small-computer procedure for optimal filtering of haemodynamic data. PMID- 4021565 TI - A microprocessor-electrocardiograph. PMID- 4021566 TI - Beat-to-beat interval measurement in the electrocardiogram. PMID- 4021567 TI - Theoretical assessment of the effect of flow maldistributions on the mass transfer efficiency of artificial organs. PMID- 4021568 TI - Estimation of the ligaments' role in maintaining foot stability using a kinematic model. PMID- 4021569 TI - Selective activation of muscles using peripheral nerve electrodes. PMID- 4021570 TI - New transcutaneous pO2 probe based on mass spectrometry with low stirring effect. PMID- 4021571 TI - Wet-wedge spirometer for the accurate continuous measurement of ventilation under anaesthesia. PMID- 4021572 TI - Automated laser light scattering system for assessment of sperm motility. PMID- 4021573 TI - Calibration of dZ/dt in impedance plethysmography. PMID- 4021574 TI - Ventricular fibrillation threshold in the dog determined with defibrillating paddles. PMID- 4021575 TI - Isolating the Medelec RS232 data interface. PMID- 4021576 TI - Use of feedback with voltage regulators for implants powered by coupled coils. PMID- 4021577 TI - Determinants of market share for a hospital's services. AB - This study identifies and analyzes factors under a hospital's control that can affect its market share. The study, utilizing the Multiplicative Competitive Interaction model, specifically focuses on determining the market share for each hospital within a geographic area, as opposed to the total demand for hospital services within an area. The results indicate that the effect of the number of physician affiliations on hospital patient share is statistically significant. The article investigates the variables that affect the level of physician affiliation. Besides physician affiliation, hospital location, a PROFILE factor based on a composite of a number of variables, and the proportion of affiliated physicians who are not affiliated elsewhere have a significant impact on each hospital's market share. The variables examined resulted in an R2 = 0.901 for individual hospital patient market share. PMID- 4021578 TI - Measurement of physician performance by standardized patients. Refining techniques for undetected entry in physicians' offices. AB - The article describes the development of methods to use live simulated patients for assessment of quality of care of primary physicians. Methods used to train patients and achieve undetected entry into physicians' practices are described. The study demonstrated that patients can be entered into practices with a low rate of detection (13%) and that they are able to recall the details of the encounter with a high degree of reliability. PMID- 4021579 TI - The rate of adoption of new procedures among physicians. The impact of specialty and practice characteristics. AB - Four hundred eighty-four physicians were surveyed on the number of new procedures they adopted during a 1-year period. Clear differences were found among specialties. A simultaneous statistical analysis of factors affecting the adoption of new procedures yielded a number of additional significant relationships. Up to an age of approximately 50 years, age has an increasing impact on the number of new procedures adopted by physicians. Beyond that age, it has a decreasing effect. Board certified physicians tend to adopt more new procedures than physicians who are not board certified. Among those physicians in nonurban locations, those in solo practice adopt significantly fewer procedures than those in other practice modes. The implications of these findings for such issues as the rising costs of health care and physician reimbursement systems are discussed. PMID- 4021580 TI - The impact of social stressors and social networks on pediatric medical care use. AB - Substantial differences in the use of pediatric medical resources reinforce the need for identifying and understanding factors that influence the use of medical services for children. This research assesses the simultaneous impact of sociodemographic characteristics, health attitudes and beliefs, psychologic distress, social stressors, and social networks on the use of pediatric acute care services during a 12-month period. Using a prospective longitudinal study design, data were obtained on 513 children and their families enrolled in a prepaid group practice. Linear modeling results showed that health attitudes and social networks were important predictors of acute care utilization in addition to child's age, birth order, baseline health status, and ethnic group. The authors were able to show significant effects for network size, dispersion, and tendency to use one's network members. Individuals with large nondispersed networks are more likely to use pediatric health services, apparently due to the transmission of the networks' pro-medical care health beliefs. Also the tendency to call on network members modifies an individual's propensity to seek care for minor pediatric medical problems and can make a difference by as much as 1.6 visits per year per child for acute care episodes. PMID- 4021581 TI - Drug choice as a problem-solving process. AB - A model of the drug prescribing process, which incorporates prescribers' personal values about treatment outcomes and beliefs about treatment effects, was tested under actual clinical conditions. Forty physicians were given two fictional case histories and six disguised case histories of patients whom they had recently treated for hypertension or maturity-onset diabetes mellitus. The physicians completed questionnaires based on each case history that measured 1) the beliefs about the probability that seven treatment-related outcomes would result from the prescribing of several alternative treatments and 2) the values placed on each outcome. The physicians were also asked, in an open-ended question, how they would treat the patient described in the case. The 40 physicians proposed 172 drug treatments that corresponded to treatment alternatives for which beliefs about treatment effects had been measured. The model correctly predicted 1) prescribing intent in 81% of hypertension cases and in 87% of the diabetes cases and 2) actual prescribing in 76% of hypertension cases and in 70% of the diabetes cases, significantly more than would be expected at random (P less than 0.01). The prescribing model appears useful for predicting drug choices for the outpatient treatment of hypertension and diabetes by resident physicians. PMID- 4021582 TI - [Transtelephonic electrocardiography: an alternative to the Holter system]. PMID- 4021583 TI - [Transtelephonic electrocardiography]. PMID- 4021584 TI - [Fibromuscular dysplasia of the carotid: an infrequent localization. Presentation of a case]. PMID- 4021585 TI - [Medical treatment of chronic subdural hematoma]. PMID- 4021586 TI - [Leukocytoclastic vasculitis as the initial manifestation of rheumatoid arthritis]. PMID- 4021587 TI - [Cryoglobulinemia: various considerations on its study and evaluation]. PMID- 4021588 TI - [Remarks on the treatment of streptococcal endocarditis]. PMID- 4021589 TI - [The Committee of Nosocomial Pathology]. PMID- 4021590 TI - [Intestinal malabsorption syndrome as the presenting form of chronic intestinal ischemia]. PMID- 4021591 TI - [Livedo reticularis and cerebral vascular accidents: Sneddon syndrome]. PMID- 4021592 TI - [Infection by delta agent in drug addicts]. PMID- 4021593 TI - [Dynamic exercise and arterial hypertension. Evaluation of the behavior of mild and moderate-severe hypertensive patients]. PMID- 4021594 TI - [Bacteremia caused by intravascular percutaneous cannulas]. PMID- 4021595 TI - [Acromegaly and empty sella turcica]. PMID- 4021596 TI - [A 75-year-old male with asthenia, anorexia, weight loss and a retroperitoneal mass]. PMID- 4021597 TI - [Malignant retroperitoneal fibrosis: clinical presentation as a single pelvic mass]. PMID- 4021598 TI - [Legionnaires' disease in Seville]. PMID- 4021600 TI - [Trends in drug utilization in Valladolid and the province]. PMID- 4021599 TI - [Prevalence of serum markers of hepatitis A and B viruses in Andalusian homosexual men]. PMID- 4021601 TI - [Declaration of tuberculosis and consumption of tuberculostatics in the provinces of Leon and Valladolid]. PMID- 4021602 TI - [Clinical evaluation of penbutolol (Hoe, 893 d) (beta adrenergic blockader), alone and in combination with hydrochlorothiazide, in the treatment of arterial hypertension. I: Effect on arterial hypertension. Comparative study of 2 parallel groups with crossed sequences by the simple-blind method]. PMID- 4021603 TI - [Treatment of non-complicated gonococcal infection with 500 mg de cefotaxime]. PMID- 4021604 TI - [Vacation camps for diabetic children]. PMID- 4021605 TI - [Gammagraphic localization of pheochromocytoma with (131I) meta iodobencylguanidine]. PMID- 4021607 TI - [Toxic oil syndrome and autoimmunity]. PMID- 4021606 TI - [Detection by analysis of dispersion of x-ray energy of silicone particles in the liver of a patient in a dialysis program]. PMID- 4021608 TI - [Immunologic considerations of toxic oil syndrome]. PMID- 4021609 TI - [Drainage of neoplastic pleuropericardial effusion]. PMID- 4021610 TI - [Chondrocalcinosis and hypophysis insufficiency]. PMID- 4021611 TI - [Acquired immunodeficiency syndrome (AIDS) in a homosexual male with tuberculosis and medullary hyperplasia]. PMID- 4021612 TI - [Folic acid deficiency caused by chronic anticonvulsive treatment. Analysis in a series of 100 epileptic patients]. PMID- 4021613 TI - [Giant cell arteritis. Multicenter study of 100 cases with positive biopsies]. PMID- 4021614 TI - [The problem of human scorpion stings (Bunthus occitanus) in the province of Cordoba]. PMID- 4021615 TI - [Giant cell arteritis: therapeutic perspectives]. PMID- 4021616 TI - [Medical histology]. PMID- 4021617 TI - [Inadequate antidiuretic hormone secretion syndrome associated with acute pneumonia. Considerations on diagnostic methods]. PMID- 4021618 TI - [Toxic encephalopathy caused by enterobacteria. Its possible relation to hyperammonemia and hypophosphatemia]. PMID- 4021619 TI - [Dosage of slow-release theophyllines: analysis of plasma levels]. PMID- 4021620 TI - [Acalculous cholecystitis and drug addiction]. PMID- 4021621 TI - [The fallacy of glycosylated hemoglobin]. PMID- 4021622 TI - [Hypercalcemia and pancreatitis]. PMID- 4021623 TI - [Pelvic lipomatosis and thrombosis of the inferior vena cava. Presentation of a case and review of the literature]. PMID- 4021625 TI - [Interictal psychopathologic manifestations in epileptics]. PMID- 4021624 TI - [Borreliosis: description of 4 cases]. PMID- 4021626 TI - [Febrile syndrome caused by giant angiofollicular hyperplasia]. PMID- 4021628 TI - [Surgical treatment of chronic subdural hematoma]. PMID- 4021627 TI - [9 cases of Merkel cell tumor published in the Spanish literature]. PMID- 4021629 TI - [Treatment of bone hydatidosis with mebendazole]. PMID- 4021630 TI - [Secondary effects of prolonged levodopa therapy in Parkinson's disease]. PMID- 4021631 TI - [Eosinophils in the broncho-alveolar lavage of diffuse interstitial lung diseases]. PMID- 4021632 TI - [Alcoholism in the general hospital. Epidemiologic study]. PMID- 4021633 TI - [Generalized morphea: systemic aspects of a skin disease. Description of 12 cases and review of the literature]. PMID- 4021634 TI - [Etiology of non-hospital pneumonias]. PMID- 4021635 TI - [Prevention of tetanus]. PMID- 4021636 TI - [The where, when, and how of care outside the hospital]. PMID- 4021637 TI - [A high-priority necessity, an unavoidable obligation: the adequate prevention of tetanus]. PMID- 4021638 TI - [The ecological view of pharmacology and antimicrobial therapy]. PMID- 4021639 TI - [Neurogenic diabetes insipidus and DIDMOAD]. PMID- 4021640 TI - [Anti-HBc IgM in HBsAg-negative chronic hepatitis]. PMID- 4021641 TI - [Hoigne syndrome. Description of 2 cases]. PMID- 4021642 TI - The use of computers and statistics in toxicology. PMID- 4021643 TI - Computers in toxicology--a perspective view. PMID- 4021645 TI - The integration of modern computer technologies for effective toxicological data handling. PMID- 4021644 TI - An interactive system for management of toxicology and teratology studies in laboratory animals. PMID- 4021646 TI - The use of computers in the Health and Safety Executive (HSE) to store information on industrial chemicals. PMID- 4021647 TI - Use of a data base management system for handling toxicity assessments of chemical materials in a motor company. PMID- 4021648 TI - Non-linear regression techniques in data analysis. PMID- 4021649 TI - The use of computers and statistics in toxicology. Technical notes. PMID- 4021650 TI - Normolipemic activities of acrylophenone derivatives with antimicrotubular properties. AB - Acrylophenone derivatives with in vitro antimicrotubular activities very similar to those of colchicine were tested on Triton WR 1339-induced hyperlipidemia in rats. They exhibit high normolipemic activity on plasmatic apolipoproteins AI and B, contrasting with inactivity on plasmatic lipids and lipoproteins. PMID- 4021651 TI - Resistance to competitive neuromuscular blocking agents in burn patients: a review. AB - The quantitative and qualitative aspects of the phenomenon of resistance to competitive (non-depolarizing) neuromuscular blocking agents in burn patients are described. The correlates and temporal features of this resistance are discussed, in addition to therapeutic approaches and the possible mechanisms underlying the resistance. PMID- 4021652 TI - Monovalent cations transfer through isolated human amnion: a new pharmacological model. AB - Transfer of monovalent cation through the isolated human amnion consists of different factors: paracellular, coupling, ATPase dependent cellular transfer, leak cellular transfer. Understanding this transfer permits testing of the action of various substances. Physiological substances (Mg, taurine) increase ionic transfer and there is a vicarious effect between Mg and taurine. The tocolytic agents MgSO4 and ethanol do not exhibit a good effect on the transfer: decrease with ethanol; equality between entry and exit fluxes with MgSO4. On the other hand, amphotericin B increases mother-to-fetus transfer. Polluting metals (Pb, Cd, Hg, As) dramatically reduce exchanges and almost completely inhibit amnion permeability. Ingestion of ethanol also exhibits a dramatic effect on the exchange between mother and fetus through the amnion. Study of ionic transfer in vitro can be considered a pharmacological model to investigate the modifications of mother-fetus exchanges by various substances. PMID- 4021653 TI - Simple method for prediction and estimation of the hemodialysability of incorporated drugs. AB - This paper describes a simple method for measuring the hemodialysability of incorporated drugs, including mathematical equations. The method furnishes preliminary drug data in early phase I investigation. Relevance of the obtained results is shown by comparison with the established literature. PMID- 4021654 TI - [Endocrine ophthalmopathy and autoimmune thyroid diseases]. PMID- 4021655 TI - [The functional result of an ileal reservoir with ileoanal anastomosis]. PMID- 4021656 TI - [Fatal aplastic anemia after acetazolamide therapy]. PMID- 4021657 TI - [Functional problems with the arm after breast cancer surgery can be repaired]. PMID- 4021658 TI - [Decreased incidence of syphilis among homosexual men as a consequence of AIDS?]. PMID- 4021659 TI - [Hypercalcemia and kidney function disorders after abuse of antacids]. PMID- 4021660 TI - [Psychiatric handicaps in childhood--occurrence, diagnosis and analysis]. PMID- 4021661 TI - [Compression therapy after acute venous thrombosis of the leg. Good results with a teamwork model]. PMID- 4021662 TI - [Retrospective cohort study shows: total low mortality among stevedores but an increasingly high risk for cancer morbidity]. PMID- 4021663 TI - [Ambulatory ophthalmologic care in Lund 1976-1983: redistribution made resources available for new needs]. PMID- 4021665 TI - [Surgical treatment of colonic ileus caused by stenosing colonic carcinoma]. PMID- 4021664 TI - [Histamine in tuna fish made 2 young people emergency cases]. PMID- 4021666 TI - [Traumatic bronchial rupture]. AB - Two cases of complete broncho-ruptures are reported. The diagnosis was established after admission to the clinic, the immediate dressing and reanastomosis of the ruptured bronchi had no essential effects on the function of the lungs. All parameters were in the region of the lower standard. The bronchus or tracheal rupture concerns mainly young patients with an elastic thorax. As regards older patients with a rigid thorax, this group is to a large extent prone to a series of fractured ribs and grave injuries of the organs. A series of fractured ribs in juvenile patients can be completely non-existent. It should be noted that the indication for a bronchoscopy is meeting with too great a reserve. Three quarters of all broncho-ruptures thus are not diagnosed. Even if after a number of years a successful reanastomosis is still possible, the functional detriments of delayed anastomoses are not always reversible. In the hands of a skilled surgeon the emergency bronchoscopy with rigid and flexible instruments is also possible in the case of very severely injured patients. PMID- 4021667 TI - [Tumors of the small intestine--diagnosis, therapy and prognosis]. AB - Between 1965 and 1983 91 patients suffering from primary tumors of the small intestine underwent surgical treatment. These patients comprise 1.24% of the total number having gastrointestinal tumors in that period. In 33% exact preoperative diagnosis was set. The delay in establishing diagnosis (6.3 months) was due to nonspecific symptoms. The majority of patients underwent operation because of vital indication without former specific investigation. Benign tumors could be resected radically without lethality. Curative resection could be performed in 62.5% and palliative resection in 37.5% of malignant lesions. Surgical lethality was 17.8%. The most common histologic type were the adenocarcinoma at one side and the adenoma at the other. The 5-year-survival-rate for curatively resected patients ranged from 60% for carcinoids, 25% for carcinomas up to 20% for lymphomas. The mean survival rate for patients who underwent curative resection was 44.12 months, for those with palliative treatment 13.37 months. 18 patients, 51.4% of the curatively treated group, are still alive, mean follow-up time being 5 years. Rareness, challenge in diagnosis, surgical procedures, postoperative complications, reoperation frequency and long term prognosis seen from various points of view are discussed. Our study emphasizes the importance of thorough gastroenterologic investigation of patients with tumor-suspective abdominal symptoms and the eminence of explorative laparotomy as final diagnostic and therapeutic step as well as the postulation for ultimate surgical radicality. PMID- 4021668 TI - [Current aspects of the surgical treatment of colonic ileus caused by stenosing colonic carcinoma]. AB - Formerly it was considered dangerous to undertake resection in the presence of colonic obstruction. This idea has been abandoned. Immediate right hemicolectomy is the accepted treatment for obstructed lesions of the right colon. For obstruction of the left colon proximal colostomy or caecostomy are being challenged by immediate resection as a Hartmann operation with iliac colostomy or finished with a colo-colonic or colo-rectal anastomosis. A subtotal colectomy with ileo-sigmoid or ileo-rectal anastomosis is a further method with encouraging experiences. From 1979-1984 a series of 33 patients with obstruction from a carcinoma of the left colon underwent emergency abdominal colectomy with primary ileosigmoidostomy or ileorectostomy without diversion. The mortality and morbidity was favourable compared with those reported in series of similar cases treated by stages procedures or primary resection. Several advantages of this method are explained and further encouraging experiences from other centers are reported. PMID- 4021670 TI - [Artificial materials in reconstructions of the middle ear]. PMID- 4021669 TI - [Fiberoptic bronchoscopy in intensive care medicine--functional efficacy and methodological side effects]. AB - A prospective study was performed to determine the side effects of fiberoptic bronchoscopy on cardiopulmonary function, the influence of bronchial lavage on cardiopulmonary function, and the functional efficacy of fiberoptic bronchoscopy in obstructive atelectasis due to retained secretions. In 17 patients endotracheal intubation was immediately followed by a significant (P less than 0.01) rise in arterial, pulmonary artery and pulmonary capillary wedge pressure, heart rate, and cardiac output. There were no statistically significant differences in arterial blood gases and intrapulmonary right-to-left shunt. Two patients showed circulatory changes indicative of a heart insufficiency on the left side. A significant increase (P less than 0.001) in intrapulmonary right-to left shunt from 12% to 17.5%, a significant decline in arterial oxygen tension of 15 mm Hg, and a significant increase of cardiac output from 6.4 to 7.71/min following saline solution lavage (20 ml in each bronchus) were observed in nine patients. The results indicate that bronchial lavage is the essential mechanism for the decline in arterial oxygen tension induced by fiberoptic bronchoscopy. In patients with unstable cardiopulmonary status, the cardiovascular response during bronchoscopy may be hazardous and the bronchoscopist should be aware of the pathophysiologic side effects involved. Fifteen therapeutic bronchoscopies were performed in five critically ill patients with obstructive atelectasis, due to retained secretions. Following the procedure, Qs/Qt declined from 23.9% to 15%, cardiac output from 9.3 to 7.31/min, and arterial Po2 increased from 58.9 to 70.9 mm Hg. The differences were statistically significant (P less than 0.0001). The therapeutic value of fiberoptic bronchoscopy in the treatment of obstructive atelectasis is demonstrated by the significant improvement in cardiopulmonary status. PMID- 4021671 TI - [Aluminum oxide ceramic implants (Tubigen type) in middle ear surgery. Report of clinical experiences]. AB - Since 1980 we have used Tubingen middle ear implants of aluminum oxide in some reconstructions of the ossicular chain. So far such implants have been inserted in 129 operations on 106 patients. Follow-up examinations have been performed on 108 ears (91 patients). Post-operative observation periods have varied from 6 to 46 months, with an average duration of 22 months. In the last two years, since observing the first extrusions and imminent extrusions of implants, we have begun inserting a small autologous cartilage-perichondrium disk between implant and eardrum. Follow-up examinations have shown that insertion of cartilage lowers the rates of extrusion and imminent extrusion. It should be noted, however, that the average observation period for implants with cartilage has been somewhat shorter than for those without cartilage. Good audiometric results have been obtained with Al2O3-ceramic implants. Moreover, insertion of a cartilage-perichondrium disk demonstrably contributes to an improvement of audiometric results. As our clinical study shows, an Al2O3-ceramic implant is quite suitable for reconstructive surgery of the ossicular chain when an alloplastic implant is needed. At the same time we strongly advise insertion of a cartilage perichondrium disk between the eardrum and the implant. PMID- 4021672 TI - [Long-term results following cholesteatoma surgery]. AB - A long-term review of 140 ears in 133 patients was carried out. All ears had first been operated on in 1971 and 1972 for cholesteatoma in the E.N.T. clinic. A closed technique was used in 110 ears and in the remaining 30 ears an open technique, depending on the pneumatisation of the mastoid, the extent of the cholesteatoma, tubal function and the age and social circumstances of the patient. At that time, second-look operations were carried out on relatively few patients after a closed operation. While the short-term results were favourable, recurrent cholesteatomas still developed 8 to 10 years later; 9 were discovered at this review alone. The long-term incidence of recurrence was 25%. Recurrent cholesteatomas were found in 57% of patients who were first operated on for a cholesteatoma before the age of 21, 24% of those between 21 and 40, and 11% of those between 41 and 60. These results reaffirm the necessity for a planned second-look operation in all young patients and also the importance of outpatient follow-up over many years. PMID- 4021673 TI - [Histologic studies of radical cavities. Case reports from the Wittmaack collection]. AB - 25 serially sectioned temporal bones from Wittmaack's temporal bone collection (ENT Hospital, University of Hamburg) have been examined in which radical mastoidectomy for cholesteatoma has been performed. The microtopographical and pathohistological analysis of postoperative results shows that recurrent cholesteatoma and inflammation act together as to complications such as labyrinthitis, meningitis and brain abscess. The subepithelial layer of granulation tissues between the matrix of the cholesteatoma and the underlying bone causes bone destruction via osteitis. PMID- 4021674 TI - [The audioanalysator. A bridge between audiometry and psychoacoustics]. AB - An analyser with a system of continous sweeping frequencies and a spectrum of strongly different control signals is described here. Including the active participation of the patient and his impaired hearing a much more accurate finding of symptoms is possible than with the standard methods of audiometry. The major factors mentioned include the continuous fine testing of the sounds heard in an unlimitated choice of frequencies ranging between 20 Hz. and 20 000 Hz. with an automated search unit as well as a test for the highest tones. After brief instruction the tests are determined by the patient himself according to choice monaurally and/or binaurally depending on comparisons and corrections right/left. This leads to highly differentiated statements on the sounds heard and to comparable qualities of tone which until today have been unknown in this wide extent of variety to audiometry and audiology and which presents totally new aspects. One of the main purposes of the audioanalyser is to detect the role played by the transients in discrimination. Obviously also the highest tones influence the character of the transients. They are apt to be easily lost e.g. by infections any kind. A vigilant patient will become aware of this loss. PMID- 4021675 TI - [Significance of electrocochleography within the scope of audiologic diagnosis]. AB - Despite the extensive applicability of brainstem evoked response audiometry (= BERA), electrocochleography (= ECochG) occupies an undisputed place among audiological diagnostic methods. It is useful, among other things, in the early identification or confirmation of hearing defects in children, since it permits measurement of the auditory threshold and of the characteristics of the suprathreshold area, and may aid in excluding ambiguous findings resulting from subjective audiometric or other objective audiometric methods in certain cases. In this regard, it makes possible a valid early prescription of hearing aids to children with auditory defects; in addition, in certain cases it provides valuable additional information and can be employed in solving simulation and masking problems. The diagnostic validity of ECochG in Meniere's disease requires continued investigation. To sum up, we can say that ECochG should be performed only at centres where the frequency of examinations guarantees the necessary expert knowledge. PMID- 4021676 TI - [Screening studies with the BOEL test for the early diagnosis of hearing loss in infants. Experiences with 4,622 cases]. AB - Hearing screening with reactometry in the newborn is now being considered too expensive and fails to detect quite a number of deaf children. Conversely, experiences at the age of 8 months with BOEL-Test (a distraction test, which yields further information on visual and neurological deficiencies) have shown that it becomes possible to detect the majority of hearing defects. As this age level is quite adequate for diagnosis even of defects arising in the first year (progressive genetic deafness, deafness due to infections etc.) and considering that rehabilitation can start only after this term, the authors suggest to reserve neonatal screening only for risk cases and to retest all children with the BOEL-Test. PMID- 4021677 TI - [Prevention and correction of postoperative ectropion following lid edge incision in the treatment of orbital floor fractures]. PMID- 4021678 TI - Alternative surgical method for repair of the fractured orbital floor. PMID- 4021679 TI - The Hydrocollator steam pack revisited. PMID- 4021680 TI - Artificial eardrum for instruction in myringotomy and PE tube insertion. PMID- 4021681 TI - Invasive Aspergillus of the head and neck. AB - Invasive fungal infections of the head and neck are uncommon. The most common organism is Mucor which is classically seen in diabetic individuals in or immediately after a bout of ketoacidosis. This report outlines our experience of four cases of invasive fungal disease caused by the Aspergillus species. All four patients in this series were profoundly granulocytopenic. Three of the four patients remained profoundly immunocompromised and succumbed to infections. One patient recovered immune competence and became a long term survivor after antifungal chemotherapy and debridement of necrotic tissue. The literature on invasive Aspergillus of the head and neck is reviewed. Some recent insights in the medicine literature concerning the epidemiology of the more common pulmonary form of this invasive disease are also discussed. PMID- 4021682 TI - Malignant transformation in non-irradiated recurrent respiratory papillomatosis. AB - The clinical, radiographic and post mortem findings occurring in a 6-year-old female with a four-year history of recurrent respiratory papillomatosis (RRP) are described. At autopsy, there were two separate foci of malignant transformation (malignant degeneration) in the bronchioloalveolar papillomata. This patient is the youngest in whom such changes have been described. Malignant transformation is a rare occurrence and is usually seen in older patients with longstanding papillomatosis, therapeutic irradiation, or a history of smoking. Pulmonary spread represents the majority of cases with "spontaneous" malignant transformation. PMID- 4021683 TI - Fixation of laryngeal stents. AB - With the advent of the CO2 laser, the transendoscopic placement of stents and keels has become an important adjunct in the surgical treatment of laryngeal webs and stenosis. Fixation of stents, however, is often difficult and cumbersome. Here, we describe two relatively simple techniques of laryngeal stent construction, placement, and fixation. PMID- 4021684 TI - Benign parotid diseases of childhood. AB - A 25-year retrospective study of 63 pediatric surgical cases of benign parotid disease was done. Inflammatory disorders accounted for 34 of the cases. The remaining 29 non-inflammatory conditions included vasoformative, solid, and cystic lesions and were nearly always asymptomatic. PMID- 4021685 TI - Electronystagmography and audio potentials in space flight. AB - Beginning with the fourth flight of the Space Transport System (STS-4), objective measurements of inner ear function were conducted in near-zero G conditions in earth orbit. The problem of space motion sickness (SMS) was approached much like any disequilibrium problem encountered clinically. However, objective testing techniques had built-in limitations superimposed by the strict parameters inherent in each mission. An attempt was made to objectively characterize SMS, and to first ascertain whether the objective measurements indicated that this disorder was of peripheral or central origin. Electronystagmography and auditory brain stem response recordings were the primary investigative tools. One of the authors (W.E.T.) was a mission specialist on board the orbiter Challenger on the eight shuttle mission (STS-8) and had the opportunity to make direct and personal observations regarding SMS, an opportunity which has added immeasurably to our understanding of this disorder. Except for two abnormal ENG records, which remain to be explained, the remaining ENG records and all the ABR records made in the weightless environment of space were normal. PMID- 4021686 TI - Surgical section of the posterior ampullary nerve. AB - Surgical section of the posterior ampullary nerve (PAN) has been used as a form of therapy for persistent benign paroxysmal positional vertigo (BPPV). Eighteen patients were reviewed. The PAN was identified in 16 patients, 15 of whom were completely cured and one of whom had improvement of symptoms. Severe sensorineural hearing loss (SNHL) occurred in three patients. This study suggests that surgical section of the PAN is effective. The procedure is facilitated by a postauricular incision and canalplasty. PMID- 4021687 TI - Sinusitis in intensive care unit patients. AB - The ultimate source of sepsis may be difficult to pinpoint in critically ill patients with multiple possible sources of iatrogenic infection. In the last year, we have been consulted with regard to several febrile intensive care unit patients in whom sinusitis was initially identified by computerized axial tomography done for other reasons. The questions are: 1. are the x-ray findings significant; 2. is this the cause of fever and sepsis; 3. how should the patient be treated for this problem; and 4. can this be prevented. In five patients, sepsis was clearly related to sinusitis. Treatment had included nasal tubes in all six patients, and in addition, five patients had received high doses of corticosteroids while intubated. The sixth patient was a diabetic. Etiology, diagnosis, and management are discussed in detail. We believe that prolonged nasal intubation should be avoided, particularly in patients with decreased resistance to infection. Initial treatment consists of removing intranasal tubes and the administration of broad spectrum or culture specific antibiotics. Surgery is indicated in the event of persistent sepsis or secondary complications. Computerized tomography is an excellent tool for diagnosis and following response to therapy. PMID- 4021688 TI - Management of perforations of the hypopharynx and cervical esophagus. AB - Complications related to perforations of the upper aerodigestive system carry a 15% mortality. Nine cases of intraluminal injuries to the hypopharynx and cervical esophagus are reviewed. Seven were related to iatrogenic causes and two associated with foreign bodies. This study details the cause and location of the injuries, associated signs and symptoms, and the resultant morbidity. A protocol for the management of suspected perforations is outlined. PMID- 4021689 TI - Carotid arteriospasm. AB - Arteriospasm can result from manipulation or fresh blood around an artery. This myogenic reflex can spread to obliterate collateral flow and can last from minutes to days. Ischemic strokes from carotid spasm ensue neurosurgical procedures, endarterectomies, and even chiropractic manipulation. The diagnosis and prevention of arteriospasm are presented, and a patient who has carotid arteriospasm following excision of a branchial cleft cyst is detailed. If the vessel constriction is noted at surgery, topical application of a local anesthetic is effective. Transfusion, hydration, oxygenation, and maintenance of blood pressure are the cornerstones of nonoperative therapy. PMID- 4021690 TI - Tinnitus and/or hearing loss elicited by facial mimetic movement. AB - Temporary tinnitus and/or hearing loss elicited by contraction of facial mimetic muscles are often observed on the affected side in patients recovering from facial nerve paralysis and in those with facial spasm. In order to clarify the mechanism of this phenomenon, changes in auditory threshold and middle ear compliance during voluntary contraction of mimetic muscles were investigated. The results suggest that this type of tinnitus and/or hearing loss is due to nonacoustic contraction of the stapedial muscle synchronous with contraction of mimetic muscles. PMID- 4021691 TI - Brush cytology for the early detection of esophageal carcinoma among patients with upper aerodigestive malignancies. AB - The incidence of associated esophageal carcinoma (EC) among patients with upper aerodigestive tract malignancies is high. Esophageal brush cytology, as developed and evaluated as a screening device for early detection of EC among villagers of northeastern Iran, was employed to examine 56 clinic patients with known tumors of the upper aerodigestive tract on 106 occasions. Two asymptomatic EC were detected and are presented. The procedure was also used as an adjunct to endoscopy in order to monitor the response of tumors under treatment. Sensitivity of 40% and specificity of 90% were found and could be improved with more judicious application of the procedure. The use of this simple test for early detection of EC among this high risk subset of clinic patients is recommended. PMID- 4021692 TI - Elongated styloid process syndrome: intraoral versus external approach for styloid surgery. AB - Elongated styloid process is a source of craniofacial and cervical pain. This condition is characterized by a dull, nagging, pharyngeal pain and a palpatory finding in the tonsillar fossa. Radiologic demonstration of styloid elongation is readily made in most instances. The incidence and pathogenesis of the styloid syndrome are discussed and the differential diagnosis detailed. The only effective treatment is surgical shortening of the styloid process. Eight patients undergoing surgery for elongated styloids are reported and the intraoral and external surgical approaches are presented. The external cervical approach is preferred since surgical visualization is optimal and the risk of deep cervical infection is minimal. PMID- 4021693 TI - Auditory brain stem response in experimentally induced hypothyroidism in albino rats. AB - In order to elucidate the relationship between the auditory function and the thyroid state, experiments were designed to study the effect of hypothyroidism on the onset of auditory brain stem response (ABR) in 26 adult myxedematous albino rats. A state of hypothyroidism was induced by daily oral administration of 6-N propyl-2-thiouracil (PTU). In 23 out of 26 rats we found minor changes in the amplitudes of all ABR waves without any correlation with the rats' T4 variation. We noted a conspicuous, dynamic, and reversible change in the amplitude of the third wave (N3) of ABR which correlates directly with the thyroxin (T4) levels in the rats' blood. The electrophysiological finding in this report indicates a lesion in the auditory tracts in the brain stem but mainly in the second main relay station of the central auditory pathway, i.e., the superior olivary complex. PMID- 4021694 TI - Jet insufflation anesthesia for endolaryngeal laser surgery: a review of 318 consecutive cases. AB - A series of 318 patients utilizing the jet insufflation technique for laser laryngeal anesthesia was studied. The technique utilizes a foil wrapped catheter placed below the vocal cords and attached to the Sanders ventilating adapter. Two pneumothoraces in children, one dental injury and one tube ignition were noted- all without permanent sequelae. Subsequent modification in technique prevented recurrence of these complications. The results indicate that this is a safe technique for laryngeal laser surgery, providing excellent visualization of the larynx while maintaining good oxygenation and airway control. PMID- 4021695 TI - [Colitis cystica profunda--contribution to the differential diagnosis of rectum cancer]. AB - A case report is given including endoscopic and morphological findings of a 19 year old female patient with colitis cystica profunda. Diagnosis could only be established by histological examination of material which had been taken from deep layers of the rectum wall. Lesions were so close to the anal region, that no surgical resection was done, because this would had impaired continence. A review of the literature is given in addition to the case report. PMID- 4021696 TI - [Segmental chlamydia proctitis]. AB - A case report is given of a 28 year old homosexual suffering from segmental proctitis caused by Chlamydia. The patient had watery diarrhea and fever since 3 weeks. Stool specimen testing was negative in regard to Salmonella, Shigella and worm eggs. Infection with N. gonorrhoea, Herpes simplex virus, Toxoplasma gondi, Yersinia and M. tuberculosis could be excluded. Serological testing yielded results suggestive of an old lues infection successfully treated. On histological examination typical reticulocytary suppurating granuloma were found. Therapy of choice of Chlamydia-proctitis is tetracyclines. PMID- 4021697 TI - [Free cecum perforation with peritonitis as a rare complication of Crohn disease]. AB - Perforation and peritonitis as complications of severe Crohn's disease are rare. Case reports of two young female patients are given who have been treated in 1983 because of peritonitis after perforation of Crohn's disease. The only therapeutic approach making sense is elimination of the intestine affected by the disease and repeated control laparotomies with for treatment of peritonitis and controlling sufficiency of the anastomosis. These patients are at high risk because of treatment with cortisone. PMID- 4021698 TI - Radioimmunoassay of serum cortisol levels in leprosy patients with special reference to type I and type II reaction. PMID- 4021699 TI - The outpatient treatment of nerve damage in patients with borderline leprosy using a semi-standardized steroid regimen. PMID- 4021700 TI - Ocular complications in patients with leprosy in Karigiri, South India. PMID- 4021701 TI - Managerial implications of multidrug therapy. PMID- 4021702 TI - [Occurrence of hypertension in school-age children]. PMID- 4021703 TI - [Classification of vesico-ureteral reflux--a new approach]. PMID- 4021704 TI - [Histamine poisoning by scombroid fish--initial report on the first 7 epidemics registered in the region around Rijeka 1982-1984]. PMID- 4021705 TI - [Recurrent nephrolithiasis and possibilities of preventing relapses]. PMID- 4021706 TI - [A rare case of paroxysmal supraventricular tachycardia during a stress test in a top-ranking athlete]. PMID- 4021707 TI - [Chondrodysplasia punctata--report on 4 patients]. PMID- 4021708 TI - [Hyperactivity of the detrusor of the urinary bladder. Conservative therapy]. PMID- 4021709 TI - [The intravenous catheter for hemodialysis and plasmapheresis (experience with 40 catheters in 26 consecutive patients)]. PMID- 4021710 TI - [Therapeutic use of plasmapheresis using filtration in 15 patients]. PMID- 4021711 TI - [Severe hereditary metabolic diseases in neonates]. PMID- 4021712 TI - [Incidence of arterial hypertension in patients with signs of chronic pyelonephritis on intravenous urography]. PMID- 4021713 TI - [Prognosis of the course of vesico-ureteral reflux in children]. PMID- 4021714 TI - [Rare clinical manifestations of leptospirosis]. PMID- 4021715 TI - [Breast cancer in younger women]. PMID- 4021716 TI - [Inappropriate antidiuretic hormone secretion caused by carcinoma of the colon]. PMID- 4021717 TI - [Morphine poisoning in advanced age]. PMID- 4021718 TI - [A comparison of findings on computerized brain tomography with pathohistologic findings in meningioma]. PMID- 4021719 TI - [Problems of urgency and priority in diagnostic and therapeutic procedures in multiple trauma (16 years' experience 1967-1982)]. PMID- 4021720 TI - [Basic problems in the preparation and use of granulocyte transfusions]. PMID- 4021721 TI - Differential effects of DSP-4 administration on regional brain norepinephrine turnover in rats. AB - The effects of DSP-4 on brain NE levels and turnover in rats were investigated in six brain regions: cortex, hippocampus, cerebellum, brainstem, hypothalamus and locus coeruleus. Administration of 50 mg/kg of DSP-4 significantly decreased NE levels in all brain regions; greatest reductions occurred in the cortex (86% decrease) and in the hippocampus (91% decrease). Doses of DSP-4 less than 50 mg/kg did not significantly lower NE levels in other brain regions, except within the cerebellum. Levels of the NE metabolite 3-methoxy, 4-hydroxyphenylethylene glycol sulfate (MHPG-S04) declined in parallel with those of NE, except within the brainstem and the locus coeruleus. NE turnover, expressed as the ratio of the MHPG-S04 concentration to that of NE, was higher in the cortex and hippocampus than other regions in control animals, and NE turnover significantly increased only in these two areas after the administration of 50 mg/kg of DSP-4 (p less than 0.01). There were no significant changes in the levels of dopamine and a significant decrease of serotonin only in the striatum. These results indicate that DSP-4 is a neurotoxin with a strong predilection for noradrenergic neurons, that its effects vary according to brain region and that its administration increases NE turnover in those brain regions showing the greatest depletion of NE. PMID- 4021722 TI - Digoxin quinidine interaction: a pharmacokinetic study in the isolated perfused rat liver. AB - Digoxin-quinidine interaction was studied in the experimental model of isolated perfused rat liver. Neither digoxin nor quinidine were toxic to the isolated rat liver. The clearance of digoxin and quinidine by the liver was directly related to the rate of bile flow and the size of the initial dose of digoxin. In the presence of quinidine, after initial doses of digoxin of 0.5 and 1 micrograms, the concentration of digoxin in the perfusate was increased 2.5 and 3-fold. Its excretion in the bile was reduced by 45% and 20.5%, respectively (all comparisons, p less than 0.01). Digoxin concentration in the liver tissue was calculated and found to be appreciably elevated in the presence of quinidine. A reduction of about 30% (p less than 0.05) in the excretion of quinidine in the bile was observed in the presence of digoxin. Thus, a competition of digoxin and quinidine for biliary excretion was demonstrated as an underlying cause for digoxin-quinidine interaction in the isolated perfused rat liver. PMID- 4021723 TI - Effect of parenterally administered atropine on the percutaneous absorption of phencyclidine and methadone. AB - The effect of parenterally administered atropine on the previously demonstrated percutaneous absorption of phencyclidine and methadone was investigated in vivo using the hairless (SKH, hr-1/hr-1) mouse as an experimental model. At both three hours and four hours following topical application of aqueous phencyclidine hydrochloride, the mean drug concentration in liver was significantly lower in mice that had received atropine sulfate by intraperitoneal injection than in mice that had received only water by this route (3 hrs: p less than 0.01; 4 hrs: p less than 0.02). Prior to three hours no statistically significant difference was noted. In contrast, parenteral administration of atropine produced no significant effect upon the percutaneous absorption of aqueous methadone hydrochloride over a four-hour period. Atropine inhibition of absorption is likely due to cutaneous dehydration, and it may be drug-specific and/or dose-related. These findings are correlated with the previously reported ethanol inhibition of percutaneous absorption. The therapeutic implications of these observations are discussed. PMID- 4021724 TI - Effects of age and luteinizing hormone antiserum on human chorionic gonadotropin stimulated testosterone secretion in young male rats. AB - The steroidogenic capacity of young male rats of different ages was studied. Two days prior to sacrifice at 5, 10, 15, 20, 25 and 30 days of age, the rats in treatment groups were given intramuscularly either human chorionic gonadotropin (HCG) at 20 I.U. twice daily/rat or luteinizing hormone (LH) antiserum (AS) at 0.25 ml twice daily/rat. Either saline or normal sheep serum (NSS) was given to control rats. The serum and testicular testosterone concentrations in the control rats averaged 0.85 +/- 0.03 ng/ml and 1.35 +/- 0.06 ng/mg testicular protein, respectively. At day-15 the serum and testicular testosterone concentrations in the HCG-treated rats had significantly increased to 9.30 +/- 0.85 ng/ml and 11.92 ng/mg of testicular protein, respectively. At the same age, the HCG-induced higher levels of serum and testicular testosterone concentrations were significantly reduced to 2.80 +/- 0.70 ng/ml and 6.02 +/- 1.00 ng/mg protein by concomitant administration of LH/AS and HCG. Our results suggest that the testosterone production in response to HCG stimulation is age-related. It was also determined that neutralization of circulating gonadotropin in LH/AS-treated rats decreased the sensitivity of Leydig cells to gonadotropin stimulation. This in vivo model should provide an excellent opportunity for the investigation of the testicular function in developing young males. PMID- 4021725 TI - Oral administration and distribution of melatonin in human serum, saliva and urine. AB - In order to evaluate for future physiological and pharmacological studies the extent to which orally administered melatonin is found in human serum and saliva and excreted into urine we measured serum, saliva and urine concentrations of melatonin by radioimmunoassay after oral administration of 100 mg melatonin. Elevated melatonin concentrations were observed with peak values of 435 nmol/l in serum and 241 nmol/l in saliva at 60 min. Elimination was monophasic following first-order kinetics. The half-lives for serum and saliva melatonin were 41 and 38 min, respectively. The results suggest that melatonin is passively secreted into saliva which reflects closely the changes in serum melatonin. Saliva sampling is thus useful in studies on peripheral melatonin both in physiological and experimental conditions. Urinary excretion of melatonin was 0.01 % of the amount of melatonin ingested. In high-performance liquid chromatography urine extracts were found to contain also a minor unknown immunoreactive component which we suggest to be some unknown metabolite of melatonin. PMID- 4021726 TI - Use of intact rat brain cells as a model to study regulation of muscarinic acetylcholine receptors. AB - Intact rat brain cells were dissociated and used to study the regulation of muscarinic acetylcholine receptors upon exposure to muscarinic receptor agonists. Incubation of cells with carbamylcholine resulted in a time-dependent decrease in subsequent [3H]N-methylscopolamine specific binding, an effect which reached a steady state after 3 hr at 37 degrees C. This effect of carbamylcholine was dependent on the concentration of the agonist in the incubation medium and was due to a reduction in the maximal binding capacity of the receptor with no decrease in the affinity of the remaining receptors. This preparation might be useful in future studies to elucidate the mechanisms underlying the regulation of muscarinic acetylcholine receptors in the central nervous system. PMID- 4021727 TI - Fluorescence study on the interaction of salicylate with rat small intestinal epithelial cells: possible mechanism for the promoting effects of salicylate on drug absorption in vivo. AB - The water-soluble drug, salicylate, was rapidly taken up by rat small intestinal epithelial cells. Salicylate, known to enhance the absorption of poorly absorbable drugs by rectum and small intestine, caused a significant decrease in the fluorescence polarization of 1,6-diphenyl-1,3,5-hexatriene (DPH) and a slight increase in the fluorescence polarization of 8-anilino-1-naphthalene sulfonic acid (ANS) in the isolated rat small intestinal epithelial cell suspension. An increase in the membrane fluidity of epithelial cells may possibly contribute to the enhancement of drug absorption by salicylate. PMID- 4021728 TI - Blockade of a motor response by cholinergic stimulation of the toad midbrain tegmentum. AB - Application of an acid solution to the dorsal skin of conscious toads having intact nervous system induces a scratching reflex and escape movements, as well as autonomic alterations (hypertension and tachycardia) that are part of the defense response. The motor components of this response are abolished or reduced by microinjection of 60, 30, 15 or 7.5 ng carbachol into the midbrain tegmentum. The cardiovascular components, however, continue to be present, although their amplitude is reduced. The depression of the motor response is statistically significant up to 15 minutes for the 60 ng dose, up to 10 minutes for the 15 and 30 ng doses, and only up to 5 minutes for the 7.5 ng dose. The data suggest that the midbrain tegmentum may modulate the reflex motor response triggered by a noxious stimulus and also participate in the organization of the escape movements. The importance of cholinergic agents in this modulation is discussed. The persistence of the cardiovascular component of the response shows the importance of this parameter as an indicator of alert situations. PMID- 4021729 TI - Abnormal cardiac rhythm in diabetic rats. AB - A significant occurrence of abnormal rhythm was observed in perfused working hearts of diabetic rats. The incidence of arrhythmias was 19/51 in diabetics as compared with 2/38 in normal controls. In considering possible pathogenetic mechanisms, conduction system defects appear to merit particular attention. PMID- 4021730 TI - First pass metabolism of ethanol--a gastrointestinal barrier against the systemic toxicity of ethanol. AB - Both in men and rats, most of the ethanol ingested at a low dose is metabolized before it reaches the systemic circulation. Oxidation of ethanol (mainly in the stomach) accounts for the bulk of this effect. This "first pass" metabolism (FPM) may be viewed as a barrier which protects against the systemic toxicity of ethanol. This barrier can be overcome by large doses of ethanol. Its efficiency is also reduced by a decrease in gastric alcohol dehydrogenase (ADH) activity secondary to chronic alcohol consumption. PMID- 4021732 TI - Effect of hypoxic cell radiosensitizers on glutathione level and related enzyme activities in isolated rat hepatocytes. AB - A comparative study of the effect of misonidazole and novel radiosensitizers on glutathione (GSH) levels and related enzyme activities in isolated rat hepatocytes was performed. Incubation of hepatocytes with 5 mM radiosensitizers led to a decrease in the intracellular GSH level. The most pronounced decrease in cellular GSH was evoked by 2,4-dinitroimidazole-1-ethanol (DNIE); after incubation for only 15 min, GSH was hardly detected. DNIE-mediated GSH loss was dependent upon its concentration. DNIE reacted with GSH nonenzymatically as well as with diethylmaleate, while misonidazole and 1-methyl-2-methyl-sulfinyl-5 methoxycarbonylimidazole (KIH-3) did not. Addition of partially purified glutathione S-transferase (GST) did not enhance DNIE-mediated GSH loss in a cell free system. DNIE inhibited glutathione peroxidase (GSH-Px), GST, and glutathione reductase (GSSG-R) activities in hepatocytes, while misonidazole and KIH-3 did not. GSH-Px activity assayed with H2O2 as substrate was the most inhibited. Inhibition of GSH-Px activity assayed with cumene hydroperoxide as substrate and GST was less than that of GSH-Px assayed with H2O2 as substrate. GSSG-R activity was decreased by DNIE, but not significantly. Incubation of purified GSH-Px with DNIE resulted in a little change in the activity when assayed with H2O2 as substrate. PMID- 4021731 TI - Vasopressin-induced calcium increases in smooth muscle cells from spontaneously hypertensive rats. AB - Cytosolic free Ca2+ concentrations [( Ca2+]i) were measured in smooth muscle cells (SMC) from spontaneously hypertensive rats (SHR) and age and sex matched Wistar-Kyoto rats (WKY). Resting levels of [Ca2+]i were 114 +/- 6 nM and 116 +/- 5 nM in SMC from WKY and SHR, respectively. Angiotensin II (AII) induced a dose dependent large increases in [Ca2+]i in SMC. There were no significant differences in resting or AII-stimulated levels of [Ca2+]i when SMC from WKY and SHR were compared. Arg-vasopressin (AVP) caused a similar but smaller [Ca2+]i increase than AII in SMC. AVP caused larger [Ca2+]i increases in SMC from SHR than in SMC from WKY. Although concentrations of AVP higher than those ordinarily detected in plasma were necessary to obtain different responses between SHR and WKY, these differences may be related to the pathogenesis of hypertension. PMID- 4021733 TI - Metabolism of S-adenosylmethionine in rat hepatocytes: transfer of methyl group from S-adenosylmethionine by methyltransferase reactions. AB - Treatment of rats with a methionine diet leads not only to a marked increase of S adenosylmethionine synthetase in liver, but also to the increase of glycine, guanidoacetate and betaine-homocysteine methyltransferases. The activity of tRNA methyltransferase decreased with the increased amounts of methionine in the diets. However, the activities of phospholipids and S-adenosylmethionine homocysteine methyltransferases did not show any significant change. When hepatocarcinogenesis induced by 2-fluorenylacetamide progresses, the activities of glycine and guanidoacetate methyltransferases in rat liver decreased, and could not be detected in tumorous area 8 months after treatment. The levels of S adenosylmethionine in the liver also decreased to levels of one-fifth of control animals at 8 months. The uptake and metabolism of [methyl-3H]-methionine and -S adenosylmethionine have been investigated by in vivo and isolated hepatocytes. The uptake of methionine and transfer of methyl group to phospholipid in the cells by methionine were remarkably higher than those by S-adenosylmethionine. These results indicate that phospholipids in hepatocytes accept methyl group from S-adenosylmethionine immediately, when it is synthesized from methionine, before mixing its pool in the cells. PMID- 4021734 TI - Effect of endurance training and chronic isoproterenol treatment on skeletal muscle sensitivity to norepinephrine. AB - The purpose of this study was to determine the influence of metabolic stresses, such as endurance training and chronic isoproterenol treatment, on skeletal muscle sensitivity to norepinephrine. Using an isolated perfused rat hindlimb preparation, dose-response curves for skeletal muscle oxygen consumption (VO2) and vascular resistance were obtained with control, endurance trained, and isoproterenol treated rats. No significant difference was found between control and experimental groups for non-stimulated VO2. In response to NE infusion, trained rats showed a significantly greater increase in VO2 compared to control rats while the response of the isoproterenol treated rats was of the same magnitude as the one for their respective control rats. At the highest dose of NE infused, the vasopressor response was significantly lower in trained rats compared to control rats. At none of the doses was there a significant difference in the vasopressor response between control and isoproterenol treated rats. These results suggest that repeated exposures to high levels of catecholamines, as produced during endurance training, leads to an increased sensitivity of skeletal muscle to the effect of norepinephrine. PMID- 4021735 TI - Direct radioimmunoassay (RIA) of salivary testosterone: correlation with free and total serum testosterone. AB - Simple and sensitive direct RIA for determination of salivary testosterone was developed by using RSL NOSOLVEX TM (125 1) kit produced by Radioassay System Laboratories (Carson, California). In addition, a relationship between salivary and serum free and total testosterone concentrations was studied in randomly selected 45 healthy subjects, 5 females on oral contraceptive pills and 28 hypertensive patients on various treatment regimens. The lowest weight of testosterone detectable by our modified method was equivalent to 1 pg/ml of saliva, taking into account analytical variability. Intra- and interassay coefficients of variation were 5.09 +/- 2.7% and 8.2 +/- 5.9% respectively. Statistically significant correlations were found between salivary and serum free testosterone (r = 0.97) and salivary and serum total testosterone concentrations (r = 0.70-0.87). The exception to this was a group of hypertensive females in which no correlation (r = 0.14) between salivary and total serum testosterone was found. It is also of interest that, while salivary testosterone was significantly increased in subjects taking oral contraceptives and most of the hypertensive patients the total serum testosterone concentration was in normal range. Our findings suggest that determination of salivary testosterone is a reliable method to detect changes in the concentration of available biologically active hormone in the circulation. PMID- 4021736 TI - Brain NADH and jumping behavior in the rat. AB - The effects of either the reduced Nicotinamide Adenine Dinucleotide (NADH) microinjected into the brain or amphetamine injected peritoneally on jumping behavior were observed in 68 rats. The enhanced jumps in the group with amphetamine are the greatest among the three experimental groups. The enhanced effect of NADH microinjected into the caudate nucleus is stronger than those of NADH in the frontal cortex. The effects of extra NADH in the frontal cortex on the jumps are dose-dependent. NADH concentrations in the brain of rats with amphetamine increased immediately after behavioral procedure. The increased concentrations in the brain from both extra and intra sources are related to the enhanced jumps of rats. PMID- 4021737 TI - Amelioration of hypoxemia by neuromuscular blockade following brain injury. AB - Brain injury has been commonly associated with respiratory failure and uncontrolled skeletal muscle activity. In the present study, neuromuscular (NM) blockade induced by injection of succinylcholine hydrochloride was used to block uncontrolled muscle contractions in dogs with brain injury caused by rapid elevation of intracranial pressure (ICP). Decerebrate posturing, a decrease in value (mean +/- SEM) of arterial oxygen tension (Pa02) of 26 +/- 1 torr, and an increase in arterial carbon dioxide tension (PaCO2) of 11 +/- 1 torr occurred in the dogs, which were supported by mechanical ventilation. The arterial hypoxemia developed independently of the decerebration; however, dogs that demonstrated decerebrate posturing exhibited significantly larger decreases in Pa02 than dogs that did not (P less than 0.01). NM blockade ameliorated the effects of elevated ICP on the arterial blood gases; i.e., the amount of hypoxemia in decerebrate dogs was significantly less in dogs subjected to NM blockade than in dogs not subjected to NM blockade. It is concluded that uncontrolled skeletal muscle activity that exacerbates arterial hypoxemia associated with brain injury is ameliorated by use of NM blockade as a therapeutic adjunct to mechanical ventilation. PMID- 4021738 TI - Stress-induced consumption of ethanol by rats. AB - Rats were maintained in a continuous choice situation for consumption of either 0.1% aqueous saccharin or 10% ethanol- 0.1% saccharin with daily tube position reversal and 24 hour fluid consumption measurement. After a stabilized baseline was achieved, groups were exposed to either no stress, or to an unpredictable schedule of isolation or immobilization stress for 14 days. During baseline and stress-exposure periods, the rats consumed predominantly the saccharin solution. Upon cessation of the stress exposures the isolation and immobilization groups markedly increased their consumption of the ethanol solution, reaching intakes as high as 9.1 g/kg/24 hours in 2-3 weeks. In addition, after 3 weeks of ethanol consumption, placement of saccharin in both tubes resulted in the stressed animals preferentially consuming from the tube that should have contained ethanol. The results suggest that unpredictable exposure to stressful stimuli can, upon cessation of exposure, induce an alcohol consummatory behavior in rats. PMID- 4021739 TI - Altered distribution and toxicity of digitoxigenin in fasted mice. AB - Intravenous administration of digitoxigenin (DTXGN) evokes seizure episodes in mice which may be dependent on brain biogenic amines such as serotonin (5-HT). Fasting is known to have effects on both drug toxicity and brain 5-HT synthesis. The purpose of this study was to assess the effects of overnight fasting on DTXGN toxicity. The i.v. LD-50 of DTXGN was increased by 61% in fasted mice. Adjustment of DTXGN dose for the decrease in body weight of fasted mice did not alter the fasting induced protection. A loading dose of 1-tryptophan (25 mg/kg, i.p.) did not alter mortality rates in either fed or fasted mice. Cortical levels of 3H DTXGN were decreased significantly by 25% in fasted mice. Liver and blood levels were elevated significantly. These data suggest that decreased DTXGN toxicity is associated with a decrease in its distribution to the cerebral cortex and emphasize the importance of acute dietary status in the expression of drug toxicity. PMID- 4021740 TI - Two daily melatonin injections differentially induce nonshivering thermogenesis and gonadal regression in the mouse (Peromyscus leucopus). AB - Female white-footed mice (Peromyscus leucopus) were injected twice daily with 5, 10, 50, 100 micrograms melatonin (MEL) or saline. Injections were given for 7 weeks at 2 and 12 hours after lights-on under a long day (LD 16:8) photoperiod. Afternoon administration of MEL induced gonadal regression, although a dose of 50 micrograms or more was necessary to obtain a maximal response. A 5 micrograms MEL injection in the afternoon resulted in intermediate reproductive tract weights. In white-footed mice a morning MEL injection did not abolish the reproductive regression induced by an afternoon injection. Mice receiving 10, 50 or 100 micrograms MEL daily exhibited increased nonshivering thermogenesis (NST), irrespective of the timing of the injection. Daily injections of 5 micrograms MEL had little effect on NST. These observations suggest that "up and down regulation" of MEL receptors may not be important in P. leucopus. Further, the mechanism by which MEL controls reproduction is different from that for NST. PMID- 4021741 TI - Glycosphingolipids of fetal and adult sheep colonic mucosa. AB - The ganglioside and neutral glycosphingolipid composition of fetal and adult sheep colonic mucosa were characterized and compared. Mono- and tetrahexosylceramide were the major neutral glycolipids of both fetal and adult colons. Adult, but not fetal, mucosa also possessed di- and trihexosylceramide. Similarly, GD1a, GM3 and GM2 were found to be the principal gangliosides in fetal and adult tissue. Adult colonic mucosa possessed significant amounts of GT1a not present in fetal tissue. Analysis of the hydroxy and nonhydroxy fatty acids as well as of the long chain bases of the major glycosphingolipids revealed differences between these lipophilic components of glycolipids in fetal and adult colonic mucosa. The present results, therefore, indicate that both quantitative and qualitative differences in glycosphingolipid composition exist between fetal and adult sheep colonic mucosa. PMID- 4021742 TI - Evidence for distinct precursor pools for biliary cholesterol and primary bile acids in cebus and cynomolgus monkeys. AB - The abnormal metabolism and distribution of plasma lipoproteins have been associated with atherosclerosis and gallstones. To better understand the process of cholesterol excretion, a study was designed to determine whether the contribution of lipoprotein free 14C-cholesterol (as LDL or HDL) to biliary cholesterol or primary bile acids differs in two species of nonhuman primates, cebus and cynomolgus monkeys, having opposite plasma LDL/HDL ratios. Since amino acid conjugation might influence bile acid synthesis or secretion, the taurine and glycine conjugates of newly synthesized primary bile acids, cholic acid (CA) and chenodeoxycholic acid (CDCA), were measured in the species capable of conjugating with taurine or glycine (cynomolgus). After total bile acid pool washout, monkeys were infused with human LDL or HDL labeled with free 14C cholesterol, and the specific activities (SA) of biliary cholesterol and primary bile acid conjugates were determined. In both species, regardless of the lipoprotein infused, the SA of biliary cholesterol and CA were greater than those for total bile acids and CDCA, respectively. In cynomolgus, the SA of glycine conjugates was higher for CA than CDCA, while the SA of taurine conjugates was greater for CDCA than CA. Under these conditions, (i) infused lipoprotein free cholesterol (as either LDL or HDL) contributed more to biliary cholesterol than to bile acids and more to CA than to CDCA; (ii) glycine conjugated preferentially with CA rather than CDCA, while taurine was the preferred conjugate for CDCA. PMID- 4021743 TI - Modification of alkenyl chain profile in plasmalogens of rat heart mitochondria by dietary trielaidin. AB - Effects of dietary trielaidin upon the alkenyl chain profile of plasmalogens were studied using heart mitochondria of rats fed a semi-purified diet containing 10% of fat supplement in which elaidic acid accounted for 69% of total fatty acids. Alkyl substituted dioxane (ASD) derivatives of the alkenyl groups of plasmalogens were prepared and analyzed by silver nitrate TLC and by GLC on different phases (BDS and OV-275). After two months of feeding the experimental diet, 40% of the ASD contained a trans-octadecenyl chain, suggesting that dietary elaidic acid was reduced in vivo to the corresponding alcohol and incorporated into plasmalogens. There was a simultaneous decrease in the percentage of ASD containing saturated chains, but the percentage of ASD substituted with cis-octadecenyl chains was not significantly affected. These observations suggested that elaidic acid may compete with saturated fatty acids, but not with cis-octadecenoic acids during the plasmalogen biosynthesis. Feeding trielaidin did not seem to have any significant influence on the relative proportions of plasmalogens, which accounted for 11-12%, on a phosphorus basis, of total heart mitochondria phospholipids. PMID- 4021745 TI - Separation of polar from non-polar lipids. PMID- 4021744 TI - The lipid composition of the spleen and intestinal and popliteal lymph nodes in the sheep. AB - Lipids were isolated from the spleen, intestinal lymph nodes and popliteal lymph nodes, tissues of potential importance in the metabolism of lymph or lymphocytes, of the sheep. The most abundant lipid classes were the triacylglycerols, free cholesterol and phospholipids, especially phosphatidylcholine, phosphatidylethanolamine and sphingomyelin. In each lipid class, the amounts of the essential fatty acids were lower than in the corresponding lipids of lymph or plasma. The triacylglycerols of each tissue resembled those of adipose tissue in structure, rather than those of lymph or plasma. Also, the structures of the phosphatidylcholines were distinctive. The results are discussed in terms of the metabolism of lipids in lymph. It does not appear probable that lymphoid tissue can supply appreciable amounts of lipid to lymph. PMID- 4021746 TI - [Pulmonary microcirculation after distant gamma-therapy of breast and thyroid cancer (perfusion pulmoscintigraphy data)]. AB - A study was made of an effect of irradiation on pulmonary microcirculation using perfusion pulmoscintigraphy indicators. Altogether 13 breast cancer patients (9 with left-side and 4 with right-side involvement) and 9 thyroid cancer patients were examined before and after radiation therapy. Absorbed doses in breast cancer were determined by phantom measurements, for thyroid cancer by calculation. Perfusion pulmoscintigraphy with labeled albumin macroaggregate preceded and followed radiotherapy. Accumulation of the radioactivity of the drug in different pulmonary zones was taken into account. Slight changes of the microcirculation index found after irradiation, lead to a conclusion that in radiation therapy of breast cancer one can observe improvement of the blood flow in the pulmonary arterial system whereas in thyroid cancer a similar effect in the irradiated upper pulmonary zone was not marked. Irradiation of the root of the lung produces a more powerful effect on the pulmonary blood flow. Taking into account a sharp suppression of the arterial blood flow in some lung cancer patients (decreasing chemotherapy efficacy) it is suggested that change of the blood content developing after irradiation be used in the planning of combined therapy of lung cancer. PMID- 4021747 TI - [Indices of external respiration in patients with Hodgkin's disease long after irradiation of the mediastinum]. AB - The function of the respiratory organs using the results of ventilation, gas exchange and roentgenopneumopolygraphy, was analysed in 98 Hodgkin's disease patients in a state of a prolonged remission (5-12 yrs.) after radiation therapy of the mediastinum. Pulmonary ventilation disorders were revealed in 43.9% of the patients. The degree of ventilation disorders depended on the degree of expression of radiation fibrosis in the paramediastinal regions of the lungs. Usually there were no clinical signs of the revealed changes. PMID- 4021748 TI - [Changes in the lungs in radiation treatment of head and neck tumors]. AB - A study was made of the roentgenomorphological and roentgenofunctional appearance of pulmonary lesions in 120 patients with head and neck tumors during radiation therapy. Laryngeal cancer was diagnosed in 56 patients, cancer of the oral cavity in 48, and neck tumors in 16 patients. X-ray examination was done 1 month before and after the termination of gamma-beam radiotherapy, the summary focal doses varying from 40 to 75 Gy. The chief modes of lung examination were roentgenography and roentgenopneumopolygraphy. It was established that even before treatment the patients had latent signs of respiratory insufficiency. Radiotherapy, irrespective of the summary focal dose value, had a mediated effect on the lungs. One month after the discontinuation of radiotherapy the pulmonary pattern changed: its elements were enhanced and dilated, the general biomechanism of respiration impaired, particularly at the expense of reducing the respiratory mobility of the diaphragm and mediastinum, disorders of the bronchopulmonary ventilation increased. A multimodality x-ray study including roentgenopneumopolygraphy helps to detect in time regional disorders of lung function which is very important for prevention of lung complications. PMID- 4021749 TI - [The Hippocratic oath and the movement of physicians for peace against nuclear warfare]. PMID- 4021750 TI - [Combined examination of the hypophysis-adrenal cortex system in breast cancer]. AB - A multimodality radioimmunological and clinicobiochemical study showed an increase in the hydrocortisone level and a decrease in the ACTH level in breast cancer patients. Stage I, following radical mastectomy (RM). A simultaneous increase in the hydrocortisone, ACTH and aldosterone level after RM, chemotherapy, hormone therapy was noted in all patients with breast cancer, Stages II and III, with initially lowered hydrocortisone and aldosterone levels and an elevated ACTH level. After RM and radiotherapy the level of hydrocortisone decreased, that of ACTH and aldosterone and renin activity increased. Scintigraphically in Stage I breast cancer the adrenals were enlarged, after RM in some cases they remained enlarged, in other cases they returned to normal. Enlarged adrenals with a lowered contrast and enhanced obscurity of the contours were observed in Stage II and III breast cancer. After therapy the adrenals remained asymmetrical with a low contrast. PMID- 4021751 TI - [Characteristics of natural and pentacin-stimulated urinary excretion of 238Pu and 239Pu]. AB - Experiments on 350 Wistar rats receiving single i. p. doses of 238Pu and 239Pu citrate (pH 6.5) have shown that 0.73-0.84% of the administered nuclides respectively are excreted with urine on the 1st day. By the end of the study (128 260 th day) the excretion value gets stable and equals 0.013-0.018%. Change of the radionuclide excretion natural rate is described in 3 exponential equations. A significantly greater rate of 238Pu excretion was revealed as compared to that of 239Pu excretion over the period of the 2nd-35th day. Intravenous injection of pentacin at a dose of 25 mu mol/kg in one of the above periods (0.5 h, 1; 8; 32; 128 and 256th day) after administration of the nuclides enhances their excretion with urine. On administering the complex after 0.5 h radionuclide excretion was maximum (16.7-20.0%). PMID- 4021752 TI - [Effect of detector sensitivity on regional indices of pulmonary function]. AB - The paper is concerned with a qualitative assessment of the assumption of independence of sensitivity function on the anatomotopographic features of the region in a functional radionuclide study of the lungs. Sensitivity function of standard collimation detectors was calculated for the radionuclides 133Xe and 99mTc. Geometrical sizes of the studied region were determined by respective CT transversal sections. An analysis of the calculation results showed that sensitivity function depended significantly on the anatomotopographic features of the studied region. The error of measurement determined by the variability of sensitivity function, easily changed from 34 to 9%. PMID- 4021753 TI - [Optimization of the timing of dose distribution in radiation therapy]. PMID- 4021754 TI - [An information system in the evaluation of clinical and laboratory data]. PMID- 4021755 TI - [A case of constrictive pericarditis developing 14 years after irradiation of the mediastinum]. PMID- 4021756 TI - [Late radiation injuries of the skin of the head and their treatment]. AB - The authors have summed up their experience gained in the diagnosis and treatment of radiation injuries of the head and maxillofacial region developing after radiotherapy of malignant tumors (105 patients) and non-tumorous diseases (47 patients). PMID- 4021757 TI - [Radionuclide and macro-microangiographic study of pulmonary ventilation and blood flow in chronic nonspecific lung diseases]. AB - A study was made of ventilation and perfusion in 105 patients with chronic pulmonary nonspecific diseases using radiopneumography with 133Xe. A simultaneous macro-microangiographic study was made of the pulmonary artery on specimens taken after lobectomy in 35 patients with bronchiectasia in the lower lobe. The control group was composed of 35 specimens of the healthy lungs taken from unembalmed cadavers of people who died of diseases unrelated to the involvement of the respiratory system as well as from 30 healthy people after radiopneumography. Asymmetry of the distribution of ventilation and perfusion is typical of patients with bronchiectasia. It manifests itself in a significant decrease in the VLC and the blood flow in the affected zone. A simultaneous compensatory rise of perfusion was recorded. In a macro-microangiographic study a rough deformity of the vascular trunks at the level of the segmental and subsegmental vessels was marked in these patients; angles of the outgoing of vessels of the main trunk decreased significantly, the number of vessels with a winding course increased. Simultaneous anatomostructural radionuclide studies make it possible to understand more deeply the essence of a pathological process. PMID- 4021758 TI - [Analysis of 99mTc-HIDA kinetics using an adaptive model]. AB - The paper is concerned with the results of assaying hepatocyte function on the basis of an adaptive pharmacokinetic model worked out by the authors. Hepatoscintigraphy with 99mTc-HIDA was used in 3 phases: the vascular phase of RP transport (the 1st min of investigation, scintigrams with a 2 s interval), the parenchymatous phase (with a 20 s interval in subsequent 10 min), the biliary phase (with a 3 min interval). The hepatocytic phase of 99mTc-HIDA transport was evaluated on the basis of the adaptive 5-compartmental model calculating the value of transport constants. In terms of differential diagnosis, the intercompartmental constants K1,2 (blood-liver) and K2,1 (liver-blood) turned out to be the most informative. Thus the assaying of hepatocyte transport function using the proposed adaptive model helps to define the degree of liver involvement in a pathological process, to choose the therapeutic tactics and method, to evaluate its efficacy and to predict possible complications. PMID- 4021759 TI - [Computed tomography in the diagnosis of metastases of colon cancer]. AB - The authors present the results of preoperative diagnosis of metastases to the liver and retroperitoneal lymph nodes in colon cancer patients using computerized tomography (CT). Comparing CT and liver scanning the first method proved to be four times more effective. False positive and false negative results in CT were obtained in 11%, in liver scanning in 25.7%. CT made it possible to specify not only the dissemination of a tumor process but also to detect some concomitant diseases. CT can be used for a dynamic control over the efficacy of the treatment of cancer patients. PMID- 4021760 TI - [Secretion of progesterone and placental lactogen during physiological pregnancy]. AB - The authors present correlation results of the information content of the determination of progesterone as compared to those of placental lactogen. Placental lactogen was determined by means of the radioimmunoassay kit "CEA IRE SORIN", whereas progesterone by means of the Soviet kit "STERON-II-125I" produced at the Institute of Organic Chemistry, AS BSSR. It has been established that the time course of the content of placental lactogen and progesterone in the blood in uncomplicated pregnancy is of positive nature and changes simultaneously. There is every reason for a wide use of progesterone determination during complicated gestation which is as informative as placental lactogen determination but more accessible in clinical practice. PMID- 4021761 TI - [Dosimetric control in interstitial gamma-therapy of malignant vaginal tumors]. AB - Dosimetric studies were performed by means of a specially designed phantom schematically simulating the anatomy of the female pelvis, to investigate into the dose distribution of interstitial gamma-therapy. Measurements were done during the simulation of tumor irradiation in 4 regions of the vagina: in the anterior and posterior walls, in the lower and upper thirds. The urinary bladder posterior wall received the largest dose during irradiation of the anterior vaginal wall, whereas the anterior rectal wall during irradiation of the posterior vaginal wall. In comparing the calculated and experimental dosimetric data one can mark their coincidence within 20%. The authors also provide the results of a study of the radiation-hygienic working conditions of the staff responsible for administering interstitial radiation therapy. PMID- 4021762 TI - [Combined treatment of colon cancer with intensive preoperative irradiation]. AB - The paper is concerned with the results of a randomized study of surgical and combined treatment of colon cancer patients using intensive preoperative irradiation; 102 were operated upon, 43 received combined treatment. It was shown that preoperative treatment did not raise the number of complications. Combined treatment made it possible to reduce the frequency of recurrences improving the 3 year survival rates. PMID- 4021763 TI - [Mathematical model of the combined effects of ionizing radiation and hyperthermia on mammalian cells]. AB - A previously proposed mathematical model for the depiction of the effects of combined ionizing radiation and hyperthermia on yeast cells of different species was applied to the description of experimental data on mammalian cells. The model suggests that the synergistic effect of combined ionizing radiation and hyperthermia is caused by additional lethal damages arising from the interaction of "sublesions" induced by both agents. These "sublesions" are not lethal after the action of these agents, each taken alone. It has been shown that the thermal enhancement ratios are strongly determined by the ratios of radiation and hyperthermia-induced lethal damages. The model predicts that the maximal synergistic effect after a separate action of these modalities will be achieved if the former agent induces a greater part of lethal damages as compared to the latter one. It has been shown that the model depicts quantitatively the synergism of the simultaneous action of the agents used for Chinese hamster cells and predicts the maximal value of the synergistic effect, conditions under which it can be achieved and the dependence of the synergistic effect on the do se rate. PMID- 4021764 TI - [Radiosensitizing effect of hyperthermia on mouse skin in relation to temperature and time of irradiation]. PMID- 4021765 TI - [Effect of various concentrations of 3H-thymidine on the kinetics of Chinese hamster cell division]. AB - A study of the asynchronous culture of Chinese hamster fibroblasts by autoradiography has shown that the pulse (15 min) incorporation of 3H-thymidine in nuclear DNA influences the kinetics of labeled cell proliferation. The results obtained suggest that one of the early biological effects of the pulse incorporation of 3H-thymidine is a delay in the occurrence of the first mitosis. With the concentration of 3H-thymidine 37 kBq/ml the slowing down of of the movement of labeled cells in the cycle is detected by a shift and overlapping of waves of labeled and unlabeled mitotic cells. In an increase of the concentration up to 370-925 kBq/ml the pattern of the curves of labeled mitotic cells is distorted. These distortions are well interpreted by the nature of change of the index of labeled and unlabeled mitotic cells. A lowered index of labeled nuclei points to a decrease in the proliferative activity of labeled cells. After an increase in 3H-thymidine concentration from 37 up to 370-925 kBq/ml the mitotic activity of cells labeled at the end of S-phase decreases from 1 to 0.6-0.1% respectively. With the concentration of 925 kBq/ml for these cells incorporating 3H-thymidine at the end of S-phase, a delay of the entry into mitosis reaches 6-8 h. Autoradiography data with the assessment of granule density suggest that mitotic activity and the period of delay in the occurrence of mitosis depend on the dose of irradiation with intranuclear tritium. Thus the tritium dose rate after 15 min of incubation with 3H-thymidine is 0.03, 0.27 and 0.69 Gy/h for concentrations 37,370 and 925 kBq/ml respectively. PMID- 4021767 TI - [Infrared and ultrahigh-frequency thermography in breast cancer]. PMID- 4021766 TI - [Structure of DNA from the rat thymus during prolonged exposure to tritium oxide and external gamma-irradiation]. AB - Thymus depopulation, DNA destruction as estimated according to the level of single-stranded breaks (SSB) and DNA structural derangement revealed by the viscosimetric assay of alkaline lysed thymocytes were observed in the course of a prolonged (1 mos) radiation exposure to tritium oxide (the 1st group) and equidimensional external gamma-irradiation (the 2nd group) in a summary dose of 10 Gy in rats. Depletion and destruction were 1.5-2 times more pronounced in case of HTO exposure. A study of the repair has revealed an increase in the number of hardly repairable or irrepairable breaks by the end of the study: by the 25th day the number of SSB repaired after additional test irradiation was O and 30% in the rats of the 1st and 2nd groups respectively. PMID- 4021768 TI - [Psychopathologic features of patients with mitral prolapse]. PMID- 4021769 TI - [Personality factors, psychological distress and "illness behavior" in patients before heart surgery]. PMID- 4021770 TI - [Behavior and psychopathology during the climacteric]. PMID- 4021771 TI - [The Beck Depression Inventory in psychosomatic research]. PMID- 4021772 TI - [Pilot community experiment for the social rehabilitation of schizophrenics]. PMID- 4021773 TI - ["Handicapped" children in normal classes. Study of a sample]. PMID- 4021774 TI - [Chronic depression. Etiologic and clinical aspects]. PMID- 4021775 TI - [Further considerations on the relation between weather conditions and epileptic seizures in the Province of Brescia]. PMID- 4021776 TI - [Treatment of anxious-depressive syndromes with Mianserin hydrochloride. Statistical evaluation of the data by Student's "t test"]. PMID- 4021777 TI - [Reserpine and depression. Clinical cases]. PMID- 4021778 TI - [Benzodiazepine abstinence syndrome. Case report]. PMID- 4021779 TI - The efficiency of human movement--a statement of the problem. AB - This paper is an introduction to a multidisciplinary series of papers on the efficiency of human movement. The problem is posed by citing the example of the large variation in oxygen uptake (per kg body weight) within a typical group of subjects running at the same submaximal speed. An analog of the possible causes of this variation is presented where "set points" for biomechanical, physiological, psychological, biochemical, and other factors combine in series to influence the overall energy cost. The various definitions of "efficiency" and "economy" are considered at the whole body and the isolated muscle level, and a discussion of baseline subtraction is presented. The concept of "effectiveness" is reviewed to illustrate the interaction of skilled performance and energy cost. It is recommended that the terms "muscular efficiency," "muscle efficiency," "economy," and "effectiveness" be used in their respective contexts to replace the current diversity of overlapping and, at times, confusing terminology. PMID- 4021780 TI - A comparison between free-weight and isokinetic bench pressing. AB - The purpose of the study was to evaluate selected parameters describing performance characteristics of a free-weight and isokinetic bench press. A secondary purpose was an attempt to clarify the technique requirements essential for a successful lift. Parameters describing the free-weight condition were generated from cinematographic data (150 fps) for five trials each at 90 and 75% of the subject's maximal performance (1RM). Isokinetic data were obtained from an instrumented Cybex Power Bench Press at two speeds corresponding to the average speeds for the free-weight conditions. Despite differences, accommodation appeared to occur for both methods when the lifts were performed maximally. A "sticking region" was defined as the portion of the free-weight activity when the subjects' force application was less than the weight of the bar. No significant difference (P less than 0.05) was observed between the 90% 1RM (26.02%) and 75% 1RM (26.94%) mean relative time values for these regions. For the Cybex device, the percentage of the activity which was isokinetic was longer for the slower speeds of rotation (0.47 rad X s-1 = 70%) and steadily decreased until the movement was only 50% isokinetic at 1.74 rad X s-1. The observed relationships between applied force-time data along with anatomical considerations suggest an ideal technique for the lift. PMID- 4021781 TI - Water intoxication: a possible complication during endurance exercise. AB - Four athletes developed water intoxication (hyponatremia) during endurance events lasting more than 7 h. The etiology of the condition appears to be voluntary hyperhydration with hypotonic solutions combined with moderate sweat sodium chloride losses. The reason why the fluid excess in these runners was not corrected by increased urinary losses is unknown. When advised to drink less during prolonged exercise, three of the athletes have subsequently completed prolonged endurance events uneventfully. PMID- 4021782 TI - Endurance exercise modifies cachexia of tumor growth in rats. AB - Food intakes, body composition, skeletal muscle mass, muscle protein synthesis, and myofibrillar protein degradation were studied in normal, food-restricted (FR), and Walker 256 tumor-bearing (TB) male Sprague-Dawley rats which were exercised (E) or maintained in a sedentary state. Exercise was enforced 3 times per wk for 100 min X session-1 at 20 m X min-1 on a 13% incline for 7 wk. Tumors were transplanted 3 wk after beginning the exercise program and were allowed to grow for 29 d. Food restriction was initiated during the last 2 wk of tumor growth. Food intakes and body lipid stores were reduced in all E groups, whereas body nitrogen was reduced only in the TBS animals. All E animals had significantly higher gastrocnemius muscle/body weight ratios than their sedentary counterparts, with the greatest ratio noted for the TBE animals. Muscle protein synthesis, measured by incorporation of [3H]tyrosine into gastrocnemius muscle, was significantly depressed in both FR and TB animals. Muscle protein breakdown, estimated by urinary 3-methylhistidine excretion, was significantly elevated in TB animals and slightly increased in FR animals. The results suggest that tumor presence significantly alters protein turnover to a greater extent than elicited by food restriction alone. Additionally, although exercise may have initially protected the animal by retarding tumor growth and muscle mass depletion, in the end, the energy costs of exercise accelerated the catabolic state. PMID- 4021783 TI - [Malnutrition: realities and perspectives]. PMID- 4021784 TI - [Training of community health aides in the subject of nutrition]. AB - Struggling with nutritional diseases requires strategies to get through: the training of community health workers (C.H.W.) represents one among others. After strong arguments are made on whether or not these C.H.W. are relevant to support the community in an attempt to increase its nutritional status, some prerequisites are listed out according to certain criteria. In order to write down a complete training plan, an intervention model and a step by step approach are submitted. In developing technical and community organization skills, the C.H.W. is better off for being involved at the local level. Nevertheless information channel and the process of problem solving are keys important to consider for the C.H.W. in his social commitment, providing that concerned sectors and disciplines participate under health personnel initiatives. PMID- 4021785 TI - An experimental study of the effect of infection on microvascular anastomosis. AB - The effect of penicillin-resistant Staphylococcus aureus infection on the patency of microvascular anastomosis was studied in an experimental model. Histological and SEM studies were also performed. It was found that the presence of infection did not significantly lower the patency rate of rat femoral artery re anastomosis. PMID- 4021786 TI - Enhancement of blood flow in experimental microvascular free flaps. AB - Prolonged ischemia may result in tissue death because of the no-reflow phenomenon. By raising a flap 24 hours prior to subjecting it to ischemia, the authors have been able to significantly lengthen the ischemia interval prior to the onset of tissue death. These effects are believed to be the result of alteration of the no-reflow phenomenon. PMID- 4021787 TI - New disposable microvascular clamp. AB - A new design for a plastic microvascular clamp is described. The clamp consists of two flat blades, with eyes permitting application and removal of the clamp with cross-forceps. Closure is effected by the elasticity of a rubber ring placed around the blades, obviating the need for an articular joint or a spring mechanism. The new design simplifies production of the clamp, which is intended to be disposable, i.e., for once-only use. PMID- 4021788 TI - A digit replantation model. AB - A simple, inexpensive, reproducible, and reliable model for digital replantation is described utilizing the rabbit ear. When compared to the human digit, it provides benefits over previous models. It is of similar tissue type and characteristics. The vessels closely approximate the digit in size and number. Results are easily quantified and the opportunity for a paired control in the same animal exists. Therefore, experimental design and statistical calculations may be simplified. The model can function for either replantation or revascularization with only slight changes in its preparation. Survival rates have been over 90%. In addition, the model provides an excellent forum for the development of technical expertise in the aspiring microvascular surgeon. PMID- 4021789 TI - Empty perineurial tube graft used to repair a digital nerve: a first case report. AB - The first clinical application using the medial cutaneous nerve as an empty perineurial tube graft in a patient with sensory deficit in the index finger is described. The technique used is described and results are evaluated both qualitatively and quantitatively. Nerve regeneration is obtained through the graft. PMID- 4021790 TI - Free vascularized nerve grafts: an experimental study in the rabbit. AB - An experimental animal model of a vascularized graft is presented as an alternative to recover faster function. The technique is described and the model compared to a conventional graft in the sciatic nerve of a rabbit. Results are evaluated with histological studies and quantified using a computer to measure the thickness of the myelin sheath as a correspondence factor of regeneration. Results showed a more favorable regeneration when a vascularized graft was used. PMID- 4021791 TI - Evaluation of patency of synthetic and autogenous venous and arterial micrografts in rats. AB - Long-term patency rates of synthetic and autogenous venous and arterial microvascular grafts in rats were compared. The grafts were interposed between the carotid arteries. The geometry of the anastomoses was designed in a manner intended to be comparable to the situation commonly encountered in cerebral revascularization procedures in man. Patency rates were 37.5% for synthetic grafts, 90% for venous grafts, and 60% for arterial grafts. Venous grafts are the best currently available microvascular prostheses. PMID- 4021792 TI - Effect of sympathectomy on microvascular anastomosis in the rat. AB - An operative technique of lumbar sympathectomy in the rat is described. Two days following either sympathectomy or sham-sympathectomy, bilateral femoral arterial anastomoses were performed by a 1-year trained microsurgeon (S.A.H.) and patency was assessed by preoperative and postoperative (30 minutes, daily) operative invasive and noninvasive techniques using an electromagnetic flow meter (for immediate postoperative) and Doppler, respectively. Of 112 rats, three and one postoperative deaths occurred within 24 hours following abdominal surgery in each group, respectively. Of 105 anastomoses in the sympathectomy group, 103 (98%) and 101 (96%) had patent anastomoses 30 minutes and 14 days postoperatively, respectively, while 109 of the sham-sympathectomy group had 105 (96%) and 103 (94%) patencies at the same period of the observation, respectively. Thus the sympathectomy did not much alter the microvascular patency rate in the rat. It appears therefore that the meticulous microvascular anastomosis cannot be replaced by lumbar sympathectomy in the rat. PMID- 4021794 TI - National Institute of Child Health and Human Development: research program on mental retardation. PMID- 4021793 TI - Debridement and replantation of the spleen with microsurgical restoration of blood flow. AB - Splenectomy continues to be the most commonly chosen method of management of traumatic injury to the spleen. However, patients of all age groups who have undergone splenectomy have significant impairment of immune functions as demonstrated by decreased production of IGM, tufsin, and properdin. This immune deficiency has been clinically manifested by an increased incidence of postsplenectomy pneumonia and sepsis which is reduced but not eliminated by the use of pneumococcal vaccine and/or prophylactic antibiotics. This paper presents the results of a study of the feasibility of repair and replantation of injured spleens using microsurgical techniques. Twenty cats had their spleens removed, finger-fractured, and debrided. The cats were then assigned to one of four groups. Group I had the entire spleen replanted but only 75% of the parenchyma revascularized. Group II had 75% of the parenchyma revascularized and replanted. Group III had 50% revascularized and replanted, and Group IV 25% revascularized and replanted. Patency of the anastomoses was assessed by postoperative arteriography. Restoration of reticuloendothelial (filter) function was assessed by the use of technetium sulphur colloid scans which showed preservation of reticuloendothelial function of the revascularized segments but absence of function in nonrevascularized segments which had been replanted. Histologic examination of replanted spleens harvested at 8 weeks showed normal architecture of red and white pulp in all areas that had been revascularized. However, in those spleens where the entire spleen had been replanted but only partially revascularized, the nonrevascularized segments were degenerated and atrophic. PMID- 4021795 TI - Symposium: residential institutions. Institutions: what is going on? PMID- 4021796 TI - Stability of residential facilities for people who are mentally retarded, 1977 1982. PMID- 4021797 TI - Staffing ratios in public institutions for persons with mental retardation in the United States. PMID- 4021798 TI - Placement decisions and their effects on the development of individuals with severe mental retardation. PMID- 4021800 TI - Work attendance in competitive employment: comparison between employees who are nonhandicapped and those who are mentally retarded. PMID- 4021799 TI - Effects of a self-recording procedure on the attending to task behavior and academic productivity of adolescents with multiple handicaps. PMID- 4021801 TI - Involuntary euthanasia and current attempts to define persons with mental retardation as less than human. PMID- 4021802 TI - Catabolism of branched-chain amino acids by diaphragm muscles of fasted and diabetic rats. AB - In vitro catabolism of branched-chain amino acids, leucine and valine, was investigated using diaphragm muscles from normal, streptozotocin-diabetic and overnight fasted rats. Oxidation and transamination of [1-14C] branched-chain amino acids were both stimulated to a similar extent by diabetes or fasting, when diaphragms were incubated with glucose. Transamination of leucine and valine was increased when diaphragms were incubated with pyruvate; stimulation of transamination was greatest in diaphragms from diabetic rats. Leucine and valine oxidation by control diaphragms was inhibited by pyruvate while it was unchanged or slightly stimulated in diaphragms from fasted or diabetic rats. Thus diaphragms from diabetic rats oxidized two to threefold more branched-chain amino acids than controls when they were incubated with pyruvate. The specific radioactivity of extracellular alpha-ketoisocaproate (KIC; the product of leucine transamination) produced by diaphragms incubated with [14C]leucine was similar for all groups (fed, fasted, or diabetic) in the presence or absence of pyruvate. Oxidation of [1-14C]KIC by diaphragms from fasted or diabetic rats, incubated with glucose, was the same or less than KIC oxidation by control diaphragms. Incubation with pyruvate inhibited KIC oxidation by control diaphragms to a significantly greater degree than that by diaphragms from diabetic or fasted rats. These data suggest the following Flux through branched-chain amino acid transaminase is limited by the availability of amino group acceptors in diaphragms from normal and overnight fasted rats, and to a greater extent in diaphragms from diabetic rats. Flux through the transaminase may be a major determinant of accelerated branched-chain amino acid oxidation by diaphragms in fasting and diabetes. In diaphragms of fasted and diabetic rats, flux through the branched-chain alpha-ketoacid dehydrogenase complex is resistant to inhibition by pyruvate, which is normally observed in controls. PMID- 4021803 TI - Vitamin E and red blood cell glutathione. AB - High doses of orally administered vitamin E (1000 IU/day) have been given to ten normal volunteers. Ten control subjects received placebo. Red blood cell glutathione was significantly higher in treated subjects than in the controls (controls: 267.5 +/- 15.7 micrograms/mL; treated: 374.8 +/- 17.3 micrograms/mL). These findings could be explained by an increase of glutathione synthesis brought about by the stimulation of glutathione synthetase activity. An alternative possibility is a reduced utilization of glutathione for the detoxification of free radicals. These two mechanisms could be effective in counteracting the glutathione content feedback of the synthetizing enzymes. PMID- 4021804 TI - Apolipoprotein B synthesis in humans: liver synthesizes only apolipoprotein B 100. AB - Apolipoprotein (apo) B-100 and B-48 are prominent apolipoproteins in VLDL, IDL, and chylomicrons. Organ cultures of normal adult human liver were established to ascertain the form of apo B synthesized by hepatocytes in humans. Human liver was minced and incubated in 15 mL methionine-free RPMI-1640 medium with 10% dialyzed fetal calf serum plus 250 microCi 35S-methionine for eight hours at 37 degrees C. Lipoproteins secreted by the liver were isolated by ultracentrifugation and the content of newly synthesized apo B determined by quantitation of radioactivity in the apoB-100 and apoB-48 bands after separation by 3% NaDodSO4 gel electrophoresis. In the eight-hour period, 2.5% to 3.2% of added 35S-methionine was secreted in TCA-precipitable protein of which 0.34% was apo B. Ninety-nine percent of the apo B in VLDL, IDL, and LDL was in the apo B-100 electrophoretic band. No significant radioactivity was detected in the apo B-48 electrophoretic band. Eighty-nine percent of the total radioactivity of apo B-100 was in VLDL with 3% and 8% in IDL and LDL, respectively. These results establish that adult human liver in organ culture synthesizes apo B-100 but not apo B-48. PMID- 4021805 TI - An in vivo study of muscle phosphate metabolism in Becker's dystrophy by 31P NMR spectroscopy. AB - The forearm flexor muscles of five patients with Becker's dystrophy were examined by the painless and noninvasive technique of high resolution phosphorus nuclear magnetic resonance spectroscopy. In the mildly affected cases, the ratios of the signals of phosphocreatine to ATP and to inorganic phosphate were normal but they were reduced in the patients with advanced disease. Absolute quantitation under the conditions of the study was not feasible, but it was probable that whereas in advanced Becker's dystrophy the intramyocellular concentration of phosphocreatine was reduced, that of ATP was unchanged. The intramyocellular pH was normal in three of the four patients in whom this could be measured and an additional unidentified signal between those of phosphocreatine and inorganic phosphate was recorded in two patients. This study emphasizes some metabolic similarities between Becker's and Duchenne type muscular dystrophy and suggests that nuclear magnetic resonance spectroscopy may be a useful and objective technique with which to investigate the biochemistry of these and other muscle diseases. PMID- 4021807 TI - Tracking of high- and low-density-lipoprotein cholesterol from childhood to young adulthood in a single large kindred with familial hypercholesterolemia. AB - Tracking of high- and low-density-lipoprotein cholesterol (HDLC, LDLC) from childhood to young adulthood was assessed in 77 children and in 53 adults from a single large pedigree with familial hypercholesterolemia who were respectively less than or equal to 19 and greater than or equal to 20 years old when first studied in 1973, with reassessment in 1984. No children and only five of the adults had received LDLC lowering therapy from 1973 to 1984. The rank correlations between the 1973 and 1984 measurements for LDLC were 0.73, 0.74, and 0.87; and for HDLC were 0.55, 0.73, and 0.65 (P less than 0.0001 for all correlations), respectively for relatives who were less than or equal to 12, 13 to 19, and greater than or equal to 20 years old in 1973. The 1973:1984 LDLC and HDLC correlations, categorized by relationships to the proband, were as follows: (1) unrelated, LDLC = 0.16, HDLC = 0.56;* (2) first-degree relatives, LDLC = 0.90, HDLC = 0.30; (3) second-degree relatives, LDLC = 0.79, HDLC = 0.39; and (4) other relatives, LDLC = 0.62, HDLC = 0.64. All nine of the probands' first-degree relatives who were above the age-sex specific LDLC 95th percentile in 1973 were also greater than the 95th percentile for LDLC in 1984. Similarly, seven of eight second-degree relatives with LDLC greater than the 95th percentile in 1973 were greater than the 95th percentile in 1984, as were ten of 15 other relatives. LDLC levels in childhood in this extended kindred were highly predictive of adult values.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4021806 TI - Hyperuricemia and hypertriglyceridemia: metabolic basis for the association. AB - Hypertriglyceridemia has been reported frequently in patients with hyperuricemia and gout. The current studies have evaluated this relationship. To examine whether hypertriglyceridemia leads to hyperuricemia, IV intralipid was given to three gouty patients. Triglycerides increased from 169 to 700 mg/dl for three hours but caused no change in serum urate level or urine uric acid and oxypurine excretion. We next examined whether high carbohydrate intake increases serum urate and triglyceride levels. Four obese patients were placed on a 2000 kcal/d sucrose diet for seven days. The serum urate increased from 6.3 +/- 1.7 to 7.9 +/ 2.0 mg/dL. The percent uric acid clearance to creatinine clearance decreased from 5.9 +/- 1.3 to the lowest mean value of 3.7 +/- 1.2, while serum triglycerides increased from 106 +/- 33 to 252 +/- 57 mg/dL and blood lactate from 607 +/- 227 to 1167 +/- 381 mumol/L. A 3000 kcal/d glucose diet in four other obese subjects produced no change in serum urate levels but increased lactate and triglyceride levels. During an isocaloric sucrose diet in two normal men, the serum urate level increased from 5.3 and 4.0 to peak values of 9.5 and 7.4 mg/dL. The percent uric acid to creatinine clearance decreased from 5.6 and 6.6 to 2.9 and 3.3. The uric acid turnover did not increase. In three gouty patients the mean serum urate increased from 8.5 +/- 1.5 to 10.6 +/- 1.4 mg/dL following an isocaloric sucrose diet. The urine uric acid excretion increased from 0.30 and 0.25 to 0.37 and 0.38 mg/mg creatinine in two patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4021808 TI - Steroids and isoprenoids. Part A. PMID- 4021809 TI - Photolabile analogs of the allylic pyrophosphate substrate of prenyltransferases. PMID- 4021810 TI - Eukaryotic prenyltransferases. PMID- 4021811 TI - Prenyltransferase from human liver. PMID- 4021812 TI - Geranylgeranylpyrophosphate synthetase of pig liver. PMID- 4021813 TI - Geranylpyrophosphate synthetase-geranylgeranylpyrophosphate synthetase from Micrococcus luteus. PMID- 4021814 TI - Hexaprenylpyrophosphate synthetase of Micrococcus luteus B-P 26. PMID- 4021815 TI - Nonaprenylpyrophosphate synthetase from Micrococcus luteus. PMID- 4021816 TI - Enzymatic synthesis of phytoene. PMID- 4021817 TI - Aspulvinone dimethylallyltransferase. PMID- 4021818 TI - 4-Hydroxybenzoate polyprenyltransferase from rat liver. PMID- 4021819 TI - Dimethylallylpyrophosphate: L-tryptophan dimethylallyltransferase. PMID- 4021820 TI - Insect 3-hydroxy-3-methylglutaryl-CoA reductase. PMID- 4021821 TI - Mevalonate 5-pyrophosphate decarboxylase from chicken liver. PMID- 4021822 TI - Use of oxygenated sterols to probe the regulation of 3-hydroxy-3-methylglutaryl CoA reductase and sterologenesis. PMID- 4021823 TI - Isopentenyldiphosphate delta-isomerase. PMID- 4021824 TI - Symposium proceedings. Screening and its scientific spin-off. Utrecht, The Netherlands, 5 October 1984. PMID- 4021825 TI - Model building on the basis of Dutch cervical cancer screening data. AB - A mass screening programme for cervical cancer is in progress in three pilot regions in The Netherlands. All women living in these regions aged 35-53 are invited to undergo screening at three-year intervals. The MISCAN simulation model was developed for the analysis and optimization of screening programmes. In this paper the model-based approach to evaluation is first outlined and then illustrated by analysing data from the first two screening rounds in the pilot regions. This analysis resulted in a rather restricted range of data-compatible assumptions for the mean duration of preclinical disease (14-19 yr) and the frequency of spontaneous regression of preinvasive lesions (45-65%), as well as a rather wide sensitivity range for the Pap smear (50-90%). These preliminary findings are compared with those of a previous MISCAN analysis of cervical cancer screening in British Columbia. On the basis of an assumed 18-yr duration, 50% regression and 70% sensitivity, a number of screening policies relating to the same age ranges but with different intervals are compared. Both the analysis and the policy comparisons are preliminary, but the findings are nevertheless reasonable and consistent with those of previous studies. A more complete MISCAN based analysis of the Dutch screening programme and subsequent optimization of screening policies will be possible when further results become available and a cost-effectiveness analysis procedure has been incorporated into the MISCAN programme. PMID- 4021826 TI - Effect of population screening for carcinoma of the uterine cervix in Finland. AB - The organization of a nationwide population-based screening programme for cervical cancer in Finland is described. The annual incidence of invasive cervical cancer decreased from about 14 to 6 cases per 100,000 during the implementation of the programme. The time trends, age specificity and comparisons with other countries support the conclusion that the organized screening programme was effective in reducing the risk. However, there is no convincing evidence in support of expanding the overall programme to cover a wider age span than 30 to 60 yr or of screening the individual woman more frequently than once every 5 yr, even though these are the current recommendations. PMID- 4021827 TI - Diagnosis analysis in breast cancer and cervical cancer screening. AB - Assessment of the accuracy of diagnostic procedures has been made independent of the diagnostic criteria used by means of Relative Operating Characteristics (ROC) analysis. A ROC curve describes the mutual relationship between the sensitivity and specificity of a diagnostic decision on the basis of various diagnostic criteria. The construction of such ROC curves is made possible if diagnoses are graded into levels of certainty. The curve enables the choice of an operating point with predetermined sensitivity and specificity values for the diagnosis decision. The population-based breast-cancer and cervical cancer screening projects carried out in Utrecht demonstrated an excellent fit between actual data and the calculated ROC curves. Analysis of the accuracy or performance of cytological diagnosis uncovered a problem arising from the similarly graded histopathological reference criteria used to determine the 'truth' of the cytological diagnosis decisions. The proposed solution is a serial calculation of ROC curves, one for each level differentiating between the histopathological categories. The ensuing three-dimensional ROC hill may reveal a summit marking numerically advantageous diagnosis criterion levels for both the test and the disease to be detected, or a depression signalling locally below-standard detection performance. PMID- 4021828 TI - Attempts to evaluate a non-randomized breast cancer screening programme (the 'DOM project'). AB - In December 1974 a non-randomized breast cancer screening programme was initiated for women born between 1911 and 1925 in the city of Utrecht (The Netherlands). The organization, response and early outcomes were encouraging. The late outcomes i.e., long-term benefits, were analysed by comparing the Utrecht findings with mortality data for other large cities in The Netherlands which do not operate screening programmes. No great differences were seen. Nevertheless, some long term benefit was forecast by a case-control study--the odds ratio of dying from breast cancer among ever-screened women compared with that in never-screened women was 0.29 (95% confidence interval: 0.14-0.62). PMID- 4021829 TI - The assessment of lead time and length bias in the evaluation of screening programmes. AB - The evaluation of screening programmes for cancer is discussed with particular reference to lead time and length bias. The epidemiological approach, concentrating on the population screened instead of the cases detected, leads to a useful evaluation of the concepts of lead time and length bias, being closely related to the natural history of the disease in question. This is shown by reviewing screening programmes for these different diseases: breast cancer, lung cancer and cervical cancer. PMID- 4021830 TI - A case-control study of endometrial cancer within a cohort. AB - In a population-based prospective study it was shown that weight, height, overweight, total body size, age at first birth, parity and age at menopause are risk factors for the development of endometrial cancer. The finding that the patients had had a higher oestrogen excretion level than the controls some time before diagnosis constitutes the biochemical background for the effect of some of the above variables. PMID- 4021831 TI - Endocrinological studies on breast cancer in the framework of a screening programme. AB - A review is presented of epidemiological investigations carried out since 1974 at Preventicon concerning hormonal aspects of the epidemiology of breast cancer. In addition, some preliminary findings are reported of a study designed to test the hypothesis of luteal insufficiency as a forerunner of cancer of the breast. PMID- 4021832 TI - Rarefication of the arterioles and capillary network in the brain of rats with different forms of hypertension. AB - The angioarchitecture of rat brain with deoxycorticosterone acetate (DOCA)-saline and renal forms of experimental hypertension were studied and compared with those of normotensive rats. The number of pial arteries of the third, fourth, and fifth order of branching was lower and their diameter smaller in hypertensive animals as compared with controls. In the medulla oblongata, pons, and mesencephalon the number of arterioles was lower and the total length of capillaries per unit volume was shorter in the experimental group. Rarefication of the capillary network was observed also in rats with spontaneous hypertension. Rarefication was found to begin at the earliest stage of developing hypertension. It was observed as soon as 24 hr after the ligation of the remaining kidney in rats with unilateral nephrectomy. A substantial decrease was recorded in the number of pial arteries with preserved lumens. The hypothesis that the rarefaction of the vascular net in the brain may lead to the formation of zones of ischemia is presented here. PMID- 4021833 TI - Microcirculation velocity changes under hypoxia in brain, muscles, liver, and their physiological significance. AB - Linear blood flow velocity in brain, muscle capillaries and hepatic sinusoids was measured by means of microfilming in normal and hypoxemic rats (breathing with 7% O2 in N2). The mean flow velocity was found to increase by 66% in brain capillaries and by 12% in hepatic sinusoids. In skeletal muscle the blood flow ceased in about 40% of the capillaries under investigation and in the others the flow velocity slowed down twofold. Different response to hypoxemia was explained by the physiological function peculiarities of the organs in question as well as the type of the energetic exchange and that of the microvascular net structure. PMID- 4021834 TI - Fenestrated capillaries in the connective tissues of the periodontal ligament. AB - A quantitative ultrastructural study was undertaken to assess the number and distribution of fenestrated capillaries in the periodontal ligaments of the rat dentition. Experiments were conducted on four animals using the right mandibular incisors and first molars. For the incisor, analysis was performed in three sites along the length of the periodontal ligament. Regardless of site, there was 0.1 fenestration per micron2 of endothelium. In the basal region, the incisor periodontal ligament contained 3.5 X 10(6) fenestrations per mm3 of tissue whereas more occlusally it contained 1 X 10(6) fenestrations per mm3 of tissue. For the molar, the capillaries showed more fenestrations, 0.4 fenestration per micron2 of endothelium. There were also more per unit volume of tissue, 12 X 10(6) fenestrations per mm3. Thus, the vasculatures of the rat incisor and molar periodontal ligaments exhibit significant numbers of fenestrations which, in the case of the incisor, are not distributed uniformly along its length. PMID- 4021835 TI - Measurements of the membrane potential of arterial smooth muscle in anesthetized animals and its relationship to changes in artery diameter. AB - Intracellular recordings of membrane potential were made from the smooth muscle of small (90-200 micron i.d.) arteries in the ears of anaesthetized guinea pigs and rabbits. Perivascular nerve stimulation evoked excitatory junction potentials and action potentials in the smooth muscle. No spontaneous muscle action potentials were recorded. Local block of perivascular nerve activity with tetrodotoxin caused a vasodilatation and a small hyperpolarization of the smooth muscle. Prazosin caused a smaller vasodilatation and no hyperpolarization. It was concluded that some of the nerve-mediated arterial tone may be caused by noradrenaline acting alpha 1-receptors, and some by some other mechanism. PMID- 4021836 TI - The microvasculature in skeletal muscle. I. Arteriolar network in rat spinotrapezius muscle. AB - A quantitative analysis of blood flow dynamics in skeletal muscle requires a detailed picture of the microvascular network. This report presents an analysis of the arteriolar network structure in the spinotrapezius muscle of the rat. The microvasculature is visualized by injection of a carbon suspension and recorded in the form of photomicrographs with a complete reconstruction of the microvasculature on transparent overlays. The spinotrapezius muscle has several major feeding arterioles which supply blood into an extensive meshwork of interconnecting or arcading arterioles spanning the entire muscle. The connections from the arcade arterioles to the capillaries are provided by transverse arterioles, which branch from the arcades at regular intervals. Each transverse arteriole forms a single asymmetric dichotomous tree and within each muscle there is a wide range in the size of transverse arterioles. A new branching schema is proposed to describe the arteriolar network. A set of network parameters is derived and typical values of these parameters in the spinotrapezius muscle of the rat are provided. PMID- 4021837 TI - The effect of long-term intraarterial norepinephrine infusion on transcapillary fluid and protein transport. AB - The effect of long-term (4 hr) intraarterial norepinephrine (NOR) infusion on vascular resistance (R), transcapillary fluid movement (Jv), and protein transport (Js) was determined in the isolated hindlimb of the dog. The limb was isolated by an occluding tourniquet and perfused at constant pressure with blood from the opposite femoral artery. Tissue volume changes were detected with a Whitney (1953) mercury-in-rubber strain gauge and protein transport assessed by direct monitoring of the rate of accumulation of 125I-albumin in the tissue. Periodically venous pressure (Pv) was elevated 20 mm Hg in order to estimate the capillary filtration coefficient (Kf) and to determine whether or not prolonged NOR exposure modified the microcirculatory response to increased pressure. Infusing NOR at a delivered dose ranging from 0.026 to 0.13 micrograms/ml significantly elevated R for the entire infusion period. Tissue volume and radioactivity declined transiently and then returned to the control level within 15 min and remained at this level for the remainder of the infusion period. These changes were attributed to blood volume shifts. Elevating Pv during NOR infusion further increased R to an extent which exceeded that during control. Jv and Js were elevated to a greater extent than during control with the delta Js exceeding delta Jv. The changes in Jv are probably due to an increase in microvascular surface area as reflected in an elevated Kf. The greater increase in Js is due in part to an increase in convective transport across a greater microvascular surface area. However, since the ratio of Js/Jv increased with Pv elevation following NOR, the increased Js may represent a change in microvascular permeability produced by the increased Pv. It is also possible that due to myogenic activity or a venous-arteriolar reflex, the microvascular pressure profile was shifted toward the venous side where the reflection coefficient is lower. PMID- 4021838 TI - Use of digital cross-correlation for on-line determination of single-vessel blood flow in the mammalian kidney. AB - The empirical relationship between erythrocyte velocity (Vrbc) and mean blood velocity (Vblood) was studied in quartz capillaries by television microscopy using the dual-slit technique. A newly designed desktop digital on-line cross correlator was combined with a computer to determine Vrbc. The accuracy of the digital correlator was tested for velocities ranging from 0 to 3 mm/sec and compared with values determined using an analog tracking correlation device. There was good agreement. Small-bore glass tubes with diameters ranging from 12 to 26 micron were perfused with suspensions of erythrocytes having hematocrits between 10 and 37%. The relationship between mean blood velocity and erythrocyte velocity in these quartz tubes was found to be Vblood = 0.88 Vrbc - 0.11, and was independent of diameter and hematocrit within the range investigated. The mean ratio for Vrbc/Vblood was 1.42 +/- 0.06. PMID- 4021839 TI - Interspecific comparison of subcutaneous tissue fluid pressure in the bat wing. AB - Tissue fluid pressures were recorded from subcutaneous tissues of three bat species by means of an improved servo-micropipet pressure recording system. Experimental animals were restrained but unanesthetized during the procedure by methods which avoided vascular occlusion. Tissue fluid pressures averaged +0.46 +/- 2.08 mm Hg (n = 12) in the Mexican free-tailed bat, +0.21 +/- 0.63 mm Hg (n = 14) in the pallid bat, and -0.31 +/- 1.01 mm Hg (n = 12) in the little brown bat. None of the average values differed significantly (P greater than 0.25) from the others or from atmospheric pressure (P greater than 0.20). Tissue fluid pressures in the subcutis of the bat were near atmospheric in agreement with the results obtained in the bat and other species by earlier investigators using both hypodermic needles and micropipets. PMID- 4021840 TI - Effects of ischemia on capillary density and flow velocity in nailfolds of human toes. AB - The purpose of this study was to investigate reactive hyperemia in the capillary network of human skin in terms of the flow per capillary and the density of flow active capillaries. Seventeen male subjects 20 to 40 years of age were seated with their right foot placed on the stage of a Leitz epi-ilumination microscope such that the nailfold capillary field in their large toes could be viewed. These vessels were video taped while flow velocity in the right posterior tibial artery was recorded via Doppler ultrasound at rest, then following a 45-sec period of arterial occlusion to the foot. Subsequent to experimentation flow velocity in single nailfold capillaries was measured via video densitometry and the number of flow-active capillaries in the field of view were counted. Following the release of arterial occlusion arterial flow velocity increased 142% above rest, the velocity in single capillaries increased by 54%, and the density of flow-active capillaries, as identified by the presence of red cells, decreased by 37%. The fact that capillary flow velocity increased to a lesser degree than arterial velocity during reactive hyperemia vis-a-vis a decrease in the number of flow active capillaries indicates that ischemia to the foot elicits a smaller dilatory effect in vascular elements controlling blood flow to the superficial cutaneous region of the toe as compared to other regional vascular networks. PMID- 4021841 TI - Exclusion of charged macromolecules in the pulmonary interstitium. AB - The polyanionic glycosaminoglycans and glycoproteins of the interstitial ground substance could influence the interstitial distribution volumes (VA) of plasma proteins filtered across the pulmonary capillaries depending upon the molecular charge of the proteins. To determine if such differences occur, two isozymes of lactate dehydrogenase (LDH) were selectively labeled with either 125I or 131I and infused simultaneously at a rate sufficient to maintain constant plasma concentrations for 24 hr. The isoelectric points of LDH 1 and LDH 5 are 5.0 and 7.9, respectively, but they have the same mol wt (140,000) and hydrodynamic radius (42 A). VA values were calculated in lymph equivalents based on the respective activities in prenodal tracheobronchial lymph. We corrected the residual blood in the tissue using either 99mTc-labeled red cells or Dextran 70 washout of blood. At 24 hr the VA for cationic LDH 5 was significantly greater than that of anionic LDH 1 (0.299 vs 0.197 ml/g wet wt) in the lung. Lymph/plasma ratios for LDH 1 and 5 were not significantly different (0.63 vs 0.58) and total extravascular lung water was not significantly different from normal. This indicates the LDH 1 was excluded from a significantly greater portion (47%) of interstitial fluid than LDH 5 (21%), and suggests an interaction of the fixed negative charges on interstitial polysaccharides with cationic proteins. PMID- 4021842 TI - Morphometric analysis of CNS microvascular endothelium. AB - The ultrastructural features that are critical to the efficient functioning of the blood-brain barrier (b-bb) were quantified in typical barrier vessels, i.e., cerebral gray and white matter capillaries, and compared with the same parameters in cerebral nonbarrier capillaries (area postrema), and in somatic capillaries, (muscle) of the mouse. The image analysis was done with the help of a simple, rapid system that required only a digitized bit pad and a microcomputer. We found that: (1) The number of pinocytotic vesicles that are thought to be associated with vascular permeability was three times higher in area postrema vessels and nearly seven times higher in muscle vessels than in barrier vessels. (2) A percentage of interendothelial junctions in nonbarrier capillaries displayed areas of separation that may represent interendothelial channels coursing from the luminal to the abluminal surface between areas of tight junctional complexes. Such areas were not observed in barrier capillaries under the normal conditions studied here, but have been seen by others under conditions in which the barrier has been breached. (3) A 39% decrease in wall thickness in barrier capillaries. (4) No differences in mitochondrial density or in area of associated pericytes among capillaries from any region. Therefore we have questioned both the universality of the apparently increased metabolic work capacity of barrier capillaries, and whether pericytes play any role in the barrier under normal conditions. PMID- 4021843 TI - The best buy--a cooperative effort. PMID- 4021844 TI - Improved communication the goal of MSMS Hospital Medical Staff Section. PMID- 4021846 TI - New MHA director calls changes a response to homogenized society. PMID- 4021845 TI - Future-shock and the medical staff. PMID- 4021847 TI - MDPH biologic products division--a hidden asset. PMID- 4021848 TI - Abortion, right and wrong. PMID- 4021849 TI - Bioluminescent assay as a potential method of rapid susceptibility testing. AB - A method of rapid susceptibility testing by bioluminescent assay was developed. Correlation between the 50% inhibition dose of antimicrobics for bacterial adenosine triphosphate measured by bioluminescent assay and the minimum inhibitory concentration obtained by the broth dilution method was satisfactory. In the bioluminescent assay the incubation time required was only 90 min. PMID- 4021851 TI - Trends of medical education in Japan. AB - This article introduces recent trends in medical education in Japan, from undergraduate education through continuing education, and explains changes in the number of medical schools and in the content of the curriculum. Some obstacles to the implementation of changes, particularly in undergraduate medical education, are discussed. Now that Japan has become relatively developed in the quantity of its health manpower and also socioeconomically, a change must be directed towards qualitative reorganization and rearrangement in medical education in line with the objectives posed for the new century. The establishment of something new is difficult; to change something old and established, however, is much more difficult. In Japan, while some new designs in the curriculum are found in almost all the new schools, any fundamental change in the established curriculum in the old schools can be found only rarely, and attempts at changing the established curriculum frequently encountered resistance in the old schools. PMID- 4021850 TI - Preliminary studies of fructan-hydrolyzing bacteria from human dental plaque. PMID- 4021852 TI - Curriculum reform: has it missed its mark? AB - An observational study of clinical teaching analyses the extent to which curriculum reforms have addressed objectives for medical education defined by community expectations. It is concluded that curriculum reforms in the school studied have resulted in a heightened awareness of patient-centred, socially responsive medical care but have failed to provide sufficient opportunities to translate that awareness into practice. Consolidation and internalization of professional skills in the non-technical aspects of medical care will require the provision of more effective clinical experiences outside the confines of tertiary care teaching hospitals. PMID- 4021853 TI - Evaluating a new approach to selecting medical students. AB - Dissatisfaction with the traditional methods of selecting Australian medical students, which use only secondary school achievement, led to an innovative alternative method at the Newcastle Medical School. This multistage approach uses tests of problem-solving ability, empathy, creativity and moral dilemmas to screen applicants otherwise suitable on academic achievement. In the 5-year trial since its inception, this process appears reasonably reliable and valid. There is some merit in using a composite score for ranking applicants, based on weighted contributions from the psychological tests used in its multifactorial battery. However, the ultimate effectiveness of individual tests of a composite score will depend on their predictive validity, which is yet unmeasured. PMID- 4021854 TI - Communication skills teaching, learning and assessment. AB - This paper outlines an introductory course in teaching communication skills to medical students in a preclinical context. The aims of the course, its content and teaching methods are described. Novel features include the active participation of selected patients in teaching and assessment, and the use of a form of role-play named 'listening triads'. The main focus of the paper is assessment, and results are recorded, relating to a class of 114 second-year students during the academic session 1983-84. Assessment of the students' learning was measured by Modified Essay Question (MEQ); students' problems face to-face with patients were identified by patients, students, and by staff members observing interactions. Problems of fitting these educational assessments into a traditional academic 'certifying' type of assessment remain unresolved at present. This course was found to be acceptable by the preclinical students, and their lack of clinical knowledge did not appear to interfere with their learning. They were enthusiastic about the supervised contact with patients, which appeared to contribute significantly to the way the course was received. PMID- 4021855 TI - Oral examinations in medical education. AB - A questionnaire survey was conducted on the nature of the oral examinations in different disciplines in the medical schools in Sri Lanka. A total of 352 students from Peradeniya and Jaffna medical faculties and pre-registration house officers, including Colombo faculty graduates of the two teaching hospitals, responded to the questionnaire. The results of the survey, which included twelve disciplines, reveal that the time duration of the oral encounter ranged from 10 to 20 minutes. The number of questions asked ranged from five to nine. Detailed analysis of the intellectual level of the questions showed that more than 63% of the questioning was at simple recall level and none at the level of problem solving. These results show that the oral examination in addition to its inherent weakness of low reliability and objectivity also lacks validity in terms of content sampling. Its predictive validity of professional competence, which requires problem-solving skills, is questionable. Content analysis of the items also revealed that all the abilities tested in the orals could best be tested in a pen-and-paper examination or a structured practical or clinical examination. PMID- 4021856 TI - Medical students' experiences in medical emergency procedures upon qualification. AB - The experiences of eighty-five final-year medical students in twenty practical procedures identified as relevant to medical emergencies were registered. Notable differences between exposures to some of these procedures within and outside teaching situations were found. Instruction must be seen as inadequate prior to first performance in real-life situations. Experiences in cardiopulmonary resuscitation were acceptable, however, while exposures to procedures with special equipment, e.g. lumbar puncture or bladder catheterization, were variable. It is concluded that opportunities may be increased by expanding already existing scheduled activities and by spending more time on planning and organization. Examples or activities in order to increase students' experiences in practical procedures during medical school are given and discussed. The problem of assessment of practical competence is pointed out as is also the need for a clear definition of the teaching objectives. PMID- 4021857 TI - Problem-based interviewing in general practice: a model. AB - A problem-based approach which can be utilized in general practice for 'diagnosis and treatment' is described. The various related phases and probable components have been defined, starting with problem sensing, problem detection, problem description and then proceeding to problem assessment and problem-oriented intervention and evaluation. This approach is empirical, patient-centered, geared to general practice, easily acquired and may well have utility in other fields of medicine. Investigation of its effectiveness and efficiency as well as its ability to be taught is needed. PMID- 4021858 TI - The educational value of being a house surgeon. AB - A time and motion study has been performed with four house surgeons. The results suggest that modern pre-registration housemen spend over 75% of their time in a hospital service role. There is only a small amount of supervised teaching in what is regarded as an educational post. PMID- 4021859 TI - Differences between conventional and problem-based curricula in their students' approaches to studying. PMID- 4021860 TI - Teaching and learning away from the medical centre. The potential contribution of new technology to continuing medical education in the United Kingdom (working document). AB - Continuing education should be convenient, relevant, individualized, systematic and include means of assessment. Educational technology provides the link between teaching and learning; it should accommodate the essential interactions between learner, instructor, environment and material. Media in open learning systems include print, audiotapes, videotapes, discs and texts, telephones, television and computers. The selection of educational techniques must reflect the particular needs and learning styles of individuals. PMID- 4021861 TI - Medical education in Canada: the situation in 1984. PMID- 4021862 TI - Education of medical students in relation to drug development, safety and efficacy. PMID- 4021863 TI - Anesthesia can be safer: the role of engineering and technology. PMID- 4021864 TI - Clinical engineering in anesthesia. AB - It is difficult to measure the effectiveness of a clinical engineering service for anesthesia objectively. Although the monitoring of service costs can justify the maintenance portion of a support effort, the real benefit derived from improvements in patient safety is less tangible. Ultimately, the number of anesthetic mishaps should decrease as a result of clinical engineering involvement in anesthesia. A comprehensive program has been in operation at Massachusetts General Hospital for four years. During that time, about 100,000 anesthesia procedures have been performed without a single patient injury related to malfunctioning equipment or to an operator error involving equipment. Although this fact may not have statistical significance, there is general agreement among the clinical staff that clinical engineering has contributed to the safe induction of anesthesia by fulfilling the goals and objectives described here. PMID- 4021865 TI - The anesthesia instrumentation and monitoring specialist. PMID- 4021866 TI - Anesthesia delivery equipment: the state of the industry. PMID- 4021868 TI - Role of the FDA in regulating the safety of anesthesia equipment. PMID- 4021867 TI - Selecting the optimal anesthesia monitoring array. PMID- 4021869 TI - Unipolar and bipolar right atrial appendage electrodes: comparison of sensing characteristics. AB - To optimize atrial sensing and reject far-field signals (i.e., ventricular potentials seen in the atrium), the atrial amplitudes of electrograms (EGMs) should be as high as possible and the ventricular amplitudes as low as possible. To compare clinical sensing results obtained with unipolar and bipolar electrodes, endocardial EGMs were recorded on a high-speed multichannel recorder with a paper speed of 200 mm/second and frequency cutoffs at 0.1 and 2,000 Hz. Forty acute unipolar and 18 acute bipolar electrodes (in different patients), three matched pairs of unipolar and bipolar electrodes, and seven coronary sinus electrodes were measured. Unipolar and bipolar right atrial appendage (RAA) electrode EGMs were compared for 1) amplitude of EGM, 2) slew rate (dv/dt); and 3) amplitude of the ventricular EGM as measured through the RAA electrode. Unipolar RAA EGMs were compared with unipolar coronary sinus EGMs. Three bipolar leads were measured as unipolar and bipolar simultaneously. Bipolar atrial EGMs had equal amplitudes (unipolar, 4.2 +/- 2.1 mV, versus bipolar, 5.9 +/- 2.5; NS), higher slew rates (unipolar, 2.6 +/- 1.6 V/second, versus bipolar, 4.4 +/- 2.1; P less than 0.005), and lower ventricular (far-field) amplitudes (unipolar, 1.1 +/- 1.1 mV, versus bipolar, 0.7 +/- 0.6; P less than 0.02) when compared with unipolar RAA electrodes. This observation was confirmed in the measurement of the matched pairs atrial/ventricular amplitude ratio (unipolar, 4.7 +/- 2.2, versus bipolar, 8.7 +/- 2.0; P less than 0.005).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4021870 TI - Microcomputer-based system for real-time computation of time-weighted average levels of ethylene oxide and other gases. AB - Accurate measurement of the time-weighted average of ethylene oxide levels down to the 1 part per million level, as mandated by OSHA, requires great attention to technique and the methods used to compute the time-weighted average. A microprocessor-based instrument that provides real-time computation and display of the time-weighted average of this or other gas levels, when used in conjunction with an analytic instrument, such as an infrared spectrophotometer, was built. The instrument provides greater accuracy than that attained with manual data collection methods, while eliminating time-consuming off-line manual computations. An overview of conventional methods, as well as a description of the new device, is presented. PMID- 4021871 TI - Prenatal genetic diagnosis. PMID- 4021872 TI - Medulloblastoma: a clinicopathological study of 42 cases. AB - Clinicopathological data have been collected for 42 patients with cerebellar medulloblastoma diagnosed and treated in Western Australia between the years 1961 and 1984. Thirty-one patients were male and 12 were over 14 years of age. In 31 patients the neoplasms were localized to the midline, while in 10 they were placed laterally in the cerebellar hemispheres. The remaining patient had a diffusely spreading neoplasm in the meninges of the posterior fossa. Thirty-nine underwent surgical treatment followed by postoperative radiotherapy. Three patients died in the early postoperative period. Twenty-four patients survived for one year or longer, 15 for two or more years, 10 for five years, and five survived longer than 10 years. The survival proportions estimated by the life table method were 66% at one year, 48% at two years and 32% at 5 and 10 years. In one patient who survived for 23 years a meningioma developed, possibly due to radiotherapy. PMID- 4021873 TI - Use of information: environmental standards, assessments of risk, prevention and clinical implications. AB - Information which relates morbidity or mortality to environmental conditions (exposure-response relationships) forms the basis for public health as well as for clinical action. For both types of action, the information base is the same, neither complete nor comprehensive. So, both types of action are based on hypothesis, the best available to explain the facts, but subject to review in the light of new facts. Even though the volume of information may be considerable, as in the case of asbestos, there are always gaps in knowledge to be bridged by judgement. This should be made on the basis of as complete an evaluation as possible of all the available evidence. PMID- 4021874 TI - Iron ore mining. Description of the industry and potential risks to health. PMID- 4021875 TI - Iron ore mining: assessing the environment. PMID- 4021876 TI - Iron ore mining: assessing morbidity. PMID- 4021877 TI - Arterial Brown-Sequard's syndrome after a penetrating injury of the spinal cord at the cervicomedullary junction. AB - A case of a 12-year-old boy, in whom a partial Brown-Sequard's syndrome developed after a gunshot injury to the back of the neck, is reported. The bullet, which was removed at operation, penetrated the left side of the spinal cord at the cervicomedullary junction. The patient recovered useful function in his left leg within a month after the injury, and was able to walk with the aid of a crutch on discharge from hospital. The case is unusual, because of the survival and subsequent good recovery of the patient after a high, penetrating injury of the spinal cord. PMID- 4021878 TI - AIDS and homologous blood transfusion. PMID- 4021879 TI - Health for all by the year 2000. PMID- 4021880 TI - RSI. PMID- 4021881 TI - Myalgic encephalomyelitis hypothesis. PMID- 4021882 TI - Can one fibre cause cancer? PMID- 4021883 TI - Contact dermatitis due to beer. PMID- 4021884 TI - Medical problems in skiers. PMID- 4021885 TI - Therapies for dementia? PMID- 4021886 TI - Public health, public policy and "neon" issues in ethics. PMID- 4021887 TI - An "acute abdomen" in Antarctica. The problems of diagnosis and management. AB - Current Australian Antarctic activities require a unique medical service: a sole medical officer is responsible for the total care of 20 to 30 expeditioners (and of himself) for around nine months a year. A case of "acute abdomen" at Casey, Antarctica, is described and the problems of diagnosis and management, in this isolated medical practice, are discussed. PMID- 4021888 TI - Prenatal genetic diagnosis. PMID- 4021889 TI - Airways disease. PMID- 4021891 TI - Weather or not. PMID- 4021890 TI - Asthma education for all. PMID- 4021892 TI - Skiing accidents. PMID- 4021894 TI - Informed consent. PMID- 4021893 TI - Hysterectomy: postoperative exercise. PMID- 4021895 TI - Mumps/measles immunization. PMID- 4021896 TI - Actinobacillus endocarditis. PMID- 4021898 TI - Torture in Iraq. PMID- 4021897 TI - Lead mobilization during pregnancy. PMID- 4021899 TI - Cimetidine vs gastroscopy. PMID- 4021900 TI - Medical problems in the Antarctic. PMID- 4021901 TI - Medical ethics: principles and practice. PMID- 4021902 TI - Kolling Institute--the first 50 years. PMID- 4021903 TI - Blame, compensation and birth defects. PMID- 4021904 TI - Is surgery for renal calculi necessary in 1985? PMID- 4021905 TI - Sexual abuse of children in Tasmania. PMID- 4021906 TI - Medical research: the new Hall Institute. PMID- 4021908 TI - Renal oncocytoma: a benign tumour on the increase. AB - Renal oncocytoma is an uncommon tumour which is being diagnosed with increasing frequency in recent years. Traditionally, these renal tumours were considered to be histological variants of renal adenocarcinomas, with no prognostic significance of their own. Several recent retrospective studies have demonstrated that they are a separate benign entity; therefore, differentiation and identification of these tumours are of the utmost importance. PMID- 4021907 TI - Haematological safety of long-term malarial prophylaxis with dapsone pyrimethamine. AB - There are no published haematological data on the long-term (more than one year) use of dapsone-pyrimethamine (Maloprim, Folaprim; one tablet a week) for malarial prophylaxis. In a study of 373 male Papua New Guinean soldiers who had used this combination for five years, we found no haematological abnormalities attributable to dapsone-pyrimethamine. Furthermore, the haematological parameters of these soldiers were not clinically different from those of Papua New Guinean university students who did not ingest antimalarial drugs prophylactically. In a parallel study, 9 of 159 white persons (6 children and 3 adult females) who had used dapsone-pyrimethamine prophylaxis for more than one year had haematological abnormalities attributable to the drug. Additionally, the mean leucocyte count of children aged 1-9 years who took dapsone-pyrimethamine was markedly lower- although within the normal range--than that of similarly aged children who received chloroquine for malarial prophylaxis. The appreciable incidence of haematological abnormalities observed in children during malarial prophylaxis with dapsone-pyrimethamine demonstrates the need to select a dose for this group on a weight rather than an age basis and to use a liquid formulation to facilitate the administration of the appropriate dose of this combination. Haematological monitoring of the long-term use of dapsone-pyrimethamine is recommended and a suitable monitoring regimen is suggested. PMID- 4021909 TI - Newborn screening for metabolic disorders in Australia and New Zealand: results for 1983. Human Genetics Society of Australasia Newborn Screening Committee. PMID- 4021910 TI - AFFPA Medical Task Force guidelines. Medical Task Force of the Australian Federation of Family Planning Associations. PMID- 4021911 TI - To kill or let die? PMID- 4021912 TI - The pathogenesis of non-ulcer dyspepsia. PMID- 4021913 TI - Health facilities for the aged. PMID- 4021914 TI - Pyloric CLO in the human stomach. PMID- 4021915 TI - Soft corneal lens infection. PMID- 4021917 TI - Smoking and Burch. PMID- 4021916 TI - The hospital discharge summary. PMID- 4021918 TI - Accidental death and the life insurance contract. PMID- 4021919 TI - [New aspects of cardiac pacemaker therapy]. PMID- 4021920 TI - [Mode of action of nootropic drugs]. PMID- 4021921 TI - [Drug allergy. 1: Mechanisms]. PMID- 4021922 TI - Vitamin supplements. PMID- 4021923 TI - Extracorporeal shock wave lithotripsy (ESWL) for urinary tract stones. PMID- 4021924 TI - Nomifensine (Merital), a new non-tricyclic antidepressant. PMID- 4021925 TI - [Simple measurements of respiration mechanics in the newborn infant]. PMID- 4021926 TI - [Hypoglycemia in small for gestational age infants]. PMID- 4021927 TI - [Recurrent apnea in the newborn infant. Study on 52 cases]. PMID- 4021928 TI - [Surveillance of congenital malformations. Experience relative to the 1982-1983 biennial]. PMID- 4021929 TI - [Clinical characteristics in 73 children with allergy to the proteins of cow's milk]. PMID- 4021930 TI - [Atopic dermatitis in the breast-fed child]. PMID- 4021931 TI - [Incidence and prevalence of juvenile onset insulin-dependent diabetes mellitus in the city and province of Turin]. PMID- 4021932 TI - [Pre-AIDS in a child of a drug-addict. Clinical and laboratory description]. PMID- 4021933 TI - [Risk factors of atherosclerosis in childhood]. PMID- 4021934 TI - [Incidence of respiratory syncytial virus infection in case records of a pediatric general medicine department]. PMID- 4021935 TI - [Segmental hypertrophy. Presentation of a case]. PMID- 4021936 TI - [Idiopathic infantile hypercalcemia. Description of a case]. PMID- 4021937 TI - [Bilateral congenital diaphragmatic eventration. Presentation of a clinical case]. PMID- 4021938 TI - [Infant nutrition during the lst year of life: proposal of an evaluation based on a score system]. PMID- 4021939 TI - [Assessment of bone mineralization and iron reserves in infants fed cow's milk and a follow-up formula]. PMID- 4021940 TI - [Lactescence of the cornea and persistence of pupillary vascularization as indicators of maturity status and gestational age of the newborn infants weighing less than l500 g]. PMID- 4021941 TI - [The NBT test as an indicator of neonatal sepsis]. PMID- 4021942 TI - [Influence of hypoxia on the EEG of patients with cystic fibrosis]. PMID- 4021943 TI - [Screening for thalassemia and/or iron deficiency in a school-age population in the community of Modugno (Bari)]. PMID- 4021944 TI - [Vaccination program required by law in a community with a predominantly rural and craft economy in Campania]. PMID- 4021945 TI - [Noonan syndrome and keratosis pilaris atrophicans faciei. Significance of dermatologic changes]. PMID- 4021947 TI - [Pseudochondroplastic spondyloepiphyseal dysplasia associated with nonfamilial congenital lymphedema and ichthyosis. Description of a case]. PMID- 4021946 TI - [Camptomelic dysplasia. A case with sex reversal]. PMID- 4021948 TI - [Effects of tocolytic therapy with ritodrine on the occurrence of neonatal hyperbilirubinemia]. PMID- 4021949 TI - [Effects of phototherapy on weight gain in neonates]. PMID- 4021950 TI - [Current epidemiology of bronchiolitis in breast-fed infants. Statistical study]. PMID- 4021951 TI - [Cri-du-chat syndrome: palmar dermatoglyphics of diagnostic significance]. PMID- 4021952 TI - [Kawasaki syndrome. Case report]. PMID- 4021953 TI - [Lymphangioma of the tongue. Apropos of 2 cases]. PMID- 4021954 TI - [Survival and long-term control of newborn infants with a birth weight under 1500 grams]. PMID- 4021955 TI - [Epidemiology of jaundice caused by maternal milk in the province of Milan. Clinical study]. PMID- 4021956 TI - [Nutrition of the child in the first year of life in the province of Ancona. Habits, environmental influences and development aspects]. PMID- 4021957 TI - [Schmidt's syndrome. Considerations and presentation of a case in childhood]. PMID- 4021958 TI - [Chilaiditi's syndrome: hepatodiaphragmatic interposition of the colon. Description of a case in childhood]. PMID- 4021959 TI - The corporate transformation of medicine in Minnesota galloping capitalism and the Twin Cities' medical marketplace. PMID- 4021960 TI - Evaluation of female urinary incontinence. PMID- 4021961 TI - Locating nonpalpable breast lesions for the surgeon. State of the art. PMID- 4021962 TI - Breast cancer and lactic acidosis. An unusual metabolic complication. PMID- 4021963 TI - Sports related injury. Part I. PMID- 4021964 TI - MMIE malpractice claim review. Internal medicine. PMID- 4021965 TI - William T. Peyton Society 1960-1985. PMID- 4021966 TI - Basic neuroscientist in a neurosurgical department. Is the experiment working? PMID- 4021967 TI - Further experience in the management of craniofacial dysmorphic states. PMID- 4021968 TI - Exploring the normal myelogram. An historical perspective. PMID- 4021969 TI - Preliminary results of a prospective randomized trial for treatment of severely brain-injured patients with hyperbaric oxygen. PMID- 4021970 TI - Neurosurgical management of selected parasitic diseases of the Western Hemisphere. PMID- 4021971 TI - Steroid hormone receptors in human meningiomas. A look at the past, present and the future. PMID- 4021973 TI - Evaluation of patients for the surgical management of epilepsy. PMID- 4021972 TI - Cerebellar cortex role of climbing fiber afferents. PMID- 4021974 TI - Brooke formula for traumatic cerebral contusion. PMID- 4021975 TI - Longterm outcome of closed head injury. PMID- 4021976 TI - A suggested relationship between sagittal synostosis, intracranial hypertension and hydrocephalus. PMID- 4021977 TI - The training in community living model: a decade of experience. PMID- 4021978 TI - A program for difficult-to-treat patients. PMID- 4021979 TI - The dissemination and impact of a model program in process, 1972-1984. PMID- 4021980 TI - Rural community support programs: the experience in three Wisconsin counties. PMID- 4021981 TI - Impact of a model program on state mental health policy development. PMID- 4021982 TI - The Bridge: an assertive outreach program in an urban setting. PMID- 4021983 TI - The evolution of the training in community living model. PMID- 4021984 TI - Ethical problems in community treatment of the chronically mentally ill. PMID- 4021985 TI - Symposium on neurosurgery. PMID- 4021986 TI - Lumbar spinal-lateral recess stenosis. AB - The syndrome of a lumbar spinal and lateral recess stenosis is characterized by pain and a variety of paresthetic symptoms occurring principally when the patient stands or walks. Sitting or lying down alleviate the symptoms promptly. The neurologic examination is characterized by a negative straight leg-raising test and a paucity of abnormal neurologic findings. The diagnosis is confirmed by a high-resolution CT scan. If conservative treatment fails, a myelogram is in order to establish a definitive diagnosis and assess the severity of neural compression prior to placing the indication for a surgical decompression of the stenotic spinal canal. The surgical procedure consists of a laminectomy and a partial facetectomy of the hypertrophied portion of the facet joint that compresses the adjacent lumbar nerve root from a dorsal direction. It is important to recognize all associated pathologic processes that must be dealt with accordingly at the same time in order to assure success of the operative procedure. The results of a surgical decompression for a lumbar spinal and lateral recess stenosis are excellent. PMID- 4021987 TI - Hepatitis B screening and vaccination in a facility for the mentally retarded. PMID- 4021988 TI - [Lymph node involvement in carcinoma of the esophagus--re-evaluation for the grouping of lymph nodes]. AB - Based on the analysis of the lymph nodes dissected during resection of 234 esophageal carcinomas and the long-term results of the patient, lymph nodes of the esophagus were grouped into 3 categories, n1, n2 and n3. The lymph nodes of n1 group were frequently involved in metastases and the long-term results of the patients with these lymph nodes metastases were excellent. The n2 lymph nodes were frequently involved in metastases but the survival rates of the patients were low. The n3 lymph nodes were rarely involved and the prognoses of the patients were poor. In comparison with the classification of lymph nodes for surgical dissection as described by the Japanese Society for Esophageal Disease, some problems in this category are discussed. However, this category was revealed to have close relation to the long-term results of the patients with carcinoma of the esophagus and was considered to be of clinical use. PMID- 4021989 TI - [The effects of hepatic ischemia on systemic blood coagulation and fibrinolysis in mongrel dogs]. AB - In order to elucidate the effects of hepatic ischemia on systemic blood coagulation and fibrinolysis, experimental study was performed. Under the heparinized hydrophilic catheter-bypass between splenic and femoral vein, the hepato-duodenal and hepato-gastric ligaments were ligated to interrupt hepatic blood inflow in 5 dogs, and temporary interruption of hepatic blood inflow for 15, 30, 60, 90 minutes were performed in each 5 dogs. In this experimental study, changes of systemic blood coagulation and fibrinolysis, and histological changes of the liver were investigated periodically. Continuous interruption of hepatic blood inflow decreased blood coagulability gradually. Temporary interruption of hepatic blood inflow for more than 60 minutes caused remarkable decrease of blood coagulability after declamp, and histologically fibrin deposits were found in sinusoid and portal vein of Glisson's area, indicating that apparent DIC occurred in the liver at more than 60 minutes after clamp. One hour after declamp of 90 minutes interruption of hepatic blood inflow, most of fibrin deposits disappeared but severe degeneration of endothelial cell of sinusoid and hepatocyte were observed, indicating the disturbance of hepatic microcirculation which caused acute liver failure and systemic DIC, finally death in shock. PMID- 4021990 TI - [New apparatus for artificial liver support: PAT resin--removal of protein-bound substances and its effect on hepatic failure in animals]. AB - Hemoperfusion using several materials such as activated charcoal is often performed to treat the patients with hepatic failure. Polyamine triglycidylisocyanulate (PAT) resin is a newly developed artificial liver support material to adsorb protein-bound substances. In this study, the effect of PAT resin on the removal of these toxic protein-bound substances was examined and following results were obtained. PAT resin adsorbed protein-bound substances selectively in vitro. Its adsorbability was superior to those of the other conventional adsorbents such as cellulose-coated charcoal, XAD-4 and XAD-7. Serum bilirubin levels were decreased by 44% in jaundiced dogs and 45% in jaundiced rabbits after 120 minutes hemoperfusion with PAT resin. Leucocyte and thrombocyte count also fell during hemoperfusion. The fall of these blood cell counts, however, was recovered by prostaglandin D2. The survival time of dogs with ischemic hepatic failure was prolonged by hemoperfusion using PAT resin. The mean survival times were 17.6 hrs in the PAT perfusion group and 10.9 hrs in the control group. The difference of survival time between these two groups was statistically significant. (p less than 0.05). These results in animals suggest that PAT resin will be clinically useful in the therapy of hepatic failure or hyperbilirubinemia. PMID- 4021991 TI - [Histopathologic study of the extrahepatic biliary system in uncorrectable congenital biliary atresia: its pathogenesis and type of atresia]. AB - Histopathologic study was carried out on specimen of extrahepatic biliary system in 23 patients with congenital biliary atresia, and the data were compared with those obtained from a control group of 43 autopsy cases of newborns and infants. In the control cases, accessory tubulo-alveolar glands were observed around the extrahepatic bile duct, and in addition some small ductules were observed in the area of the porta hepatis. In cases of biliary atresia, characteristic findings were histologically detected at each level of the extrahepatic biliary system. In the area of the porta hepatis, there were many epithelial luminal structures in fibrous tissue with inflammatory infiltrates. Near the confluence, the bile duct completely disappeared to be replaced by fibrosis, and in the area between the porta hepatis and the confluence, granulation tissue surrounded by fibrosis was observed. The epithelial luminal structures in the area of the porta hepatis were thought to originate from the bile duct, draining ductules and accessory glands observed in the normal controls. These structures tended to decrease in number with time. In cases possessing a patent common bile duct, the gallbladder showed many mucous glands and no inflammatory changes. On the other hand, in cases with an obliterated common bile duct, the gallbladder showed chronic atrophic cholecystitis without any mucous glands. The pathogenesis remains unknown, but it is thought that this disorder results from non-infectious inflammatory changes initiated near the confluence of the normally developed bile duct. PMID- 4021992 TI - [Trophic effect of caerulein on the normal pancreas and enhancement in experimental pancreatic cancer by caerulein in the Syrian golden hamster]. AB - The author investigated the hyperplastic and hypertrophic effect of caerulein in the pancreas of normal syrian golden hamsters, and the promoting effect of experimental pancreatic cancer in hamster induced by N-nitroso-bis (2 hydroxypropyl) amine (BHP). The results are as follow: Repeated subcutaneous injections of caerulein in every 12 hours for 10 days elicited a marked trophic effect on the pancreas, characterized by increased pancreatic weight and pancreatic weight/DNA ratios with an enhanced content of DNA and amylase in the pancreas in treated hamsters. DNA synthesis, as measured by histoautoradiography of tritiated thymidine labeled tissues, was increased in pancreatic acinar but little in islet nor in ductal cells. Weekly subcutaneous administration of BHP with caerulein brought pancreatic carcinomas earlier and in higher incidence than BHP alone. The majority of induced carcinomas were well differentiated adenocarcinomas, and acinar cell carcinoma was seen in neither groups. In addition, a further investigation was performed in search target cells of both BHP and caerulein. Repeated injections of caerulein in every 12 hours for 5 days before one shot of subcutaneous BHP administration led to increase both mitotic and labeling index using tritiated thymidine in most acinar cells. These results suggested that caerulein has a trophic action on the pancreas, and acts as a promotor in experimental pancreatic carcinoma. PMID- 4021993 TI - [Prevention of spinal cord ischemia after thoracic aortic occlusion]. AB - Paraplegia has been a devastating and unpredictable complication following surgical procedures necessitating temporary occlusion of the thoracic aorta. This study was undertaken to investigate the effect of the pressure gradient between the aortic pressure distal to the occlusion and cerebrospinal fluid pressure (CSFP), defined as "Relative spinal cord perfusion pressure" (RSPP) on the development of ischemia to the spinal cord by using somatosensory evoked potentials (SEP). In 30 mongrel dogs, the thoracic aorta just distal to the left subclavian artery was occluded for either 30 or 120 minutes until SEP disappeared. RSPP was maintained at 20, 30 or 40 mmHg in each dog by adjusting the degree of occlusion of th aorta and/or changing CSFP by withdrawal of cerebrospinal fluid or injection of normal saline into the subarachnoid space. SEP were recorded as a cortical response to the electrical stimulation of bilateral peroneal nerves. SEP did not disappear for 30 or 120 minutes when RSPP was 40 mmHg. It would be concluded that 40 mmHg or higher of RSPP is necessary in order to prevent the spinal cord ischemia due to the temporary occlusion of the thoracic aorta. PMID- 4021994 TI - [Histopathological study of the parathyroid gland in renal hyperparathyroidism]. AB - From July 1973 to July 1984, 50 patients underwent parathyroidectomy because of secondary hyperparathyroidism due to chronic renal failure. One hundred fifty eight excised parathyroid glands in 41 of these patients were submitted to the histopathological examinations in the relations to their clinical features which revealed the following findings. Inspite of secondary hyperparathyroidism, eleven of 41 patients showed four unevenly enlarged parathyroid glands with one or two glands weighing less than 100mg. The glands were divided into three adenomas, 101 diffusely and 54 nodulary hyperplastic glands. The nodular type hyperplasia, which had a greater proportion of clear chief cells, vacuolated chief cells, transitional oxyphil cells and oxyphil cells, was more hyperplastic than the diffuse type. The patients with the nodular type showed more advanced clinical features in the secondary hyperparathyroidism. PMID- 4021995 TI - Structural and stereochemical specificity of mouse monoclonal antibodies to the organophosphorous cholinesterase inhibitor soman. AB - To test the usefulness of immunotherapy in organophosphate poisoning, two mouse monoclonal antibodies were prepared to the chemical warfare agent soman. The antibodies bound reversibly to soman and afforded considerable protection to acetylcholinesterase in vitro. However, they were only marginally effective in preventing the consequences of soman poisoning in mice (these data have been published elsewhere). Since potential for immunotherapeutic usefulness resides in antibody affinity and specificity, we conducted experiments to define these parameters to enable us to maximize them in the production of later antibodies. Interaction of the antibodies (CC1 and BE2) in affinity-purified form with a series of soman analogs in a competitive inhibition enzyme immunoassay was used to assess the contribution to binding affinity of each functional group on the soman molecule. Neither antibody interacted with the -P = S analog of soman or methylphosphonic acid. A decrease in the number of methyl groups on the pinacolyl side chain reduced or eliminated binding with both antibodies while increasing the size of this group had a mixed result. The major metabolite of soman, its basic hydrolysis product, interacted weakly with BE2 and failed to interact with CC1. Alkyl ester group substitution at the fluorine position increased antibody binding up to the symmetrical dipinacolyl analog. Stereochemical specificity was determined by measuring the apparent decrease in the rate of inhibition of cholinesterases (acetylcholine acetylhydrolase, EC 3.1.1.7, or acylcholine acylhydrolase, EC 3.1.1.8) by pure soman stereoisomers in the presence of increasing concentrations of each antibody. CC1 demonstrated specificity that varied as C(+)P(+) less than C(-)P(+) less than C(-)P(-) less than C(+)P(-). Although affinities were much lower, BE2 also showed a preference for the more toxic P(-) isomers. PMID- 4021996 TI - Dipeptides as inhibitors of the gelation of sickle hemoglobin. AB - To examine in detail a class of peptides that inhibit the polymerization of deoxyhemoglobin S, we assayed the L-amino acids and 22 dipeptides for their effect on deoxyhemoglobin S solubility. Of the amino acids, the aromatics (phenylalanine, tyrosine, and tryptophan) significantly increased deoxyhemoglobin S solubility, as did high concentration of arginine. Combinations of the hydrophobic (specifically the aromatic) amino acids with a hydrophilic amino acid, such as arginine or lysine, resulted in dipeptides which were much more soluble than the hydrophobic or aromatic amino acid alone, and also inhibited polymerization. Furthermore, samples of deoxyhemoglobin S at 26 to 27 g/dl containing some of these dipeptides such as Arg-Trp, Arg-Phe, and Lys-Trp in excess of 50 to 100 mM did not polymerize, indicating a 1.4- to 1.6-fold increase in deoxyhemoglobin S solubility. The enhancement of polymerization, i.e., decrease in deoxyhemoglobin S solubility, observed by the addition of aspartic acid, glycine, or lysine was observed or was reduced in the dipeptides containing these hydrophilic amino acids combined with hydrophobic amino acids (valine, leucine, isoleucine, or the aromatic amino acids). The effects of these dipeptides on deoxyhemoglobin S solubility were mostly linear with concentration. However, the changes in deoxyhemoglobin S solubility by addition of a dipeptide was not simply the sum of the effects observed with the individual amino acids as exemplified by the differential effect of reversing the dipeptide sequence (e.g., Arg-Phe and Phe-Arg, or Arg-Tyr and Tyr-Arg). These data provide further evidence as to the stereospecific nature of this class of noncovalent inhibitors of deoxyhemoglobin S polymerization. PMID- 4021997 TI - ATP-dependent calcium uptake by rat liver plasma membrane vesicles. Effect of alkylating hepatotoxins in vivo. AB - Lethal cell injury from hepatotoxic drugs has been postulated to result from an alteration in cell Ca2+ homeostasis. ATP-dependent Ca2+ uptake by the plasma membrane has a sulfhydryl-dependent functional moiety and, therefore, could be vulnerable to chemically reactive drug intermediates. Thus, alkylating hepatotoxins given in vivo were examined for their ability to inhibit Ca2+ accumulation by plasma membrane vesicles isolated from livers of adult male rats. ATP-dependent Ca2+ accumulation was decreased 62% by bromobenzene, 76% by acetaminophen, and 92% by CCl4. Mitochondrial Ca2+ uptake was minimally affected by the toxins, and only CCl4 affected Ca2+ accumulation by liver microsomes. The effect of acetaminophen on plasma membrane Ca2+ uptake was apparent as early as 45 min postdose. Depletion of protective intracellular GSH by diethyl maleate treatment (400 mg/kg) alone minimally decreased control plasma membrane uptake activity, although the GSH depletion markedly potentiated the effect of acetaminophen on the plasma membrane and on necrosis. Alkylation of sites on the plasma membrane may be a key chemical-macromolecule interaction in drug-induced liver necrosis, and inhibition of plasma membrane Ca2+ regulation may provide a connecting link between the alkylation hypothesis and the perturbed Ca2+ homeostasis hypothesis of lethal cell injury. PMID- 4021998 TI - Stereoselective metabolism of 7-chlorobenz(a)anthracene by rat liver microsomes. Absolute configurations and optical purities of trans-dihydrodiol metabolites. AB - Metabolism of 7-chlorobenz(a)anthracene (7-Cl-BA) by liver microsomes from untreated rats, and from rats pretreated with either 3-methylcholanthrene or phenobarbital was studied. The metabolites were isolated by HPLC and characterized by UV-visible, mass, and proton NMR spectral analyses and identified as 7-Cl-BA trans-3,4-, 5,6-, and 8,9-dihydrodiols, 3-hydroxy-7-Cl-BA, and 4-hydroxy-7-Cl-BA. Proton NMR spectral analysis indicated that 7-Cl-BA trans 3,4-dihydrodiol preferentially adopted a quasidiequatorial conformation while trans-5,6- and 8,9-dihydrodiols preferentially adopted a quasidiaxial conformation. Comparison of circular dichroism spectra with those of 7 bromobenz(a)anthracene trans-dihydrodiol metabolites of known absolute stereochemistry indicated that the major enantiomeric 7-Cl-BA trans-3,4-, 5,6-, and 8,9-dihydrodiols had R,R absolute configuration. Application of chiral stationary phase HPLC for direct resolution of the trans-dihydrodiols and their hydrogenated and dechlorinated derivatives enabled determination of the optical purity of each dihydrodiol metabolite obtained from the three microsomal systems. In vitro incubation of 7-Cl-BA under molecular oxygen-18 produced 7-Cl-BA trans 3,4-, 5,6-, and 8,9-dihydrodiols, each containing one oxygen-18 atom. Mass spectral analysis of the dehydration products of the oxygen-18-containing trans dihydrodiol metabolites indicated that 7-Cl-BA 3S,4R-epoxide and 7-Cl-BA 8R,9S epoxide were the predominant enantiomeric intermediates. PMID- 4021999 TI - Use of mRNA hybridization and radioimmunoassay to study mechanisms of drug induced accumulation of enkephalins in rat brain structures. AB - The repeated administration of haloperidol or fenfluramine for several days led to an increase of enkephalin content in specific brain areas. In order to characterize the nature of the dynamic changes underlying this increase, we measured the content of proenkephalin mRNA (PE-mRNA), of high molecular weight (HMW) enkephalin precursors, and of low molecular weight enkephalin peptides (LMW) in various brain areas. To measure PE-mRNA, we hybridized the specific mRNA with a [32P]cDNA probe for human pheochromocytoma PE. HMW and LMW enkephalin content was measured by radioimmunoassay after separation of the immunoreactive peaks by Bio-Gel P-2 column chromatography and enzymatic digestion of the precursors. Haloperidol treatment increased enkephalins, the precursor, and PE mRNA content in the striatum, suggesting that this drug might increase enkephalin steady state by increasing transcription, translation, or both processes. In contrast, fenfluramine increased hypothalamic and striatal enkephalin content by preferentially reducing neuropeptide utilization or decreasing its catabolism without changing its synthesis. PMID- 4022000 TI - N-ethylmaleimide-induced changes in agonist affinity for histamine H1-receptors in the guinea pig brain. AB - The effect of the thiol-alkylating agent, N-ethylmaleimide (NEM), on histamine (HA) H1-receptors from guinea pig cerebellum, labeled with [3H]mepyramine, was investigated. The properties of [3H]mepyramine binding (apparent dissociation constant and maximal number of sites) were not modified by prior treatment of the membranes with 2 or 5 mM NEM. This treatment did not change either the inhibition curves of d-chlorpheniramine or mianserin, two H1-receptor antagonists. In contrast, treatments of membranes with NEM significantly decreased the IC50 values of HA and the slope indexes (pseudo Hill coefficients) of HA inhibition curves, which became inferior to unity. These effects were irreversible, and their extent related to the NEM treatment duration and the NEM concentration. A computer analysis of the data indicated that part of the H1-receptors were converted from a state of low affinity for the amine (IC50 value of 75 microM) into a high agonist affinity state (IC50 value of 2 microM). The change was less marked for partial agonists than for HA. The NEM-induced change was observed in the presence and in the absence of Na+ ions, known to decrease the affinity of HA for H1-receptors. Agonists or antagonists did not protect against the modification of HA affinity induced by NEM. The digitonin-solubilized receptors retained their sensitivity to NEM. Among other thiol reagents, iodoacetamide and iodoacetic acid were ineffective, and organic mercurial agents strongly reduced the number of [3H]mepyramine-binding sites. NEM treatment might alkylate a critical thiol group located outside the ligand-binding domain of the H1 receptor and thereby stabilize the latter in a conformation distinct from that of the activated state. PMID- 4022001 TI - Photoinactivation of serotonin uptake by an arylazido derivative of 5 hydroxytryptamine. AB - A potential photoaffinity probe for the substrate-binding polypeptide of the neuronal serotonin uptake system has been synthesized. Under dark conditions, 3 (beta-(4-azidobenzamidino)ethyl-5-hydroxyindole (serotonin azidobenzamidine (SABA) was found to inhibit competitively [3H]5-hydroxytryptamine uptake by rat cortical synaptosomes with a K1 of 130 nM. The selectivity of this action was indicated by SABA's much lower potency as an inhibitor of synaptosomal [3H]norepinephrine uptake (K1 = 7 microM). When synaptosomes were irradiated in the presence of SABA, serotonin uptake was irreversibly inhibited in a concentration-dependent fashion with the maximum effect occurring at 1 microM SABA. At this concentration, approximately 40% of the serotonin uptake activity could not be recovered upon repeated washing of the synaptosomes. This inhibition was determined not to result from the production of a potent inhibitory photolysis product of SABA. The photoinactivation of serotonin transport by SABA was found to depend on the time of irradiation and could be prevented by the presence of agents that interact with the uptake system. Serotonin, p chloroamphetamine, fenfluramine, and alaproclate protected the serotonin carrier against SABA's irreversible effects in a concentration-dependent manner. The presence of high concentrations of Tris or p-aminobenzoic acid, two nitrene scavenging agents, did not reduce the level of photoinactivation of serotonin uptake by SABA, indicating that the irreversible inhibition is a result of true photoaffinity labeling of the carrier. PMID- 4022002 TI - Characterization of the oxidation of amine metabolites of nitrotoluenes by rat hepatic microsomes. N- and C-hydroxylation. AB - The rat hepatic microsomal oxidation of amine metabolites of mono-and dinitrotoluene isomers has been investigated. Microsomes catalyzed the NADPH dependent oxidation of 2-amino-6-nitrobenzyl alcohol, 2-amino-4-nitrobenzyl alcohol, and the isomeric aminobenzyl alcohols to ethyl acetate-extractable compounds capable of reducing ferric iron. The microsomal metabolism of 2-amino-6 nitrobenzyl alcohol, a metabolite of the hepatocarcinogen 2,6-dinitrotoluene, was characterized in detail. High pressure liquid chromatographic analysis indicated the formation of two metabolites, both of which were reducing agents. One metabolite was identified as 2-hydroxylamino-6-nitrobenzyl alcohol by comparison of its chromatographic properties and mass spectrum with those of the authentic compound. Mass spectral, proton NMR, and UV-visible spectroscopic studies suggested that the other metabolite was 2-amino-5-hydroxy-6-nitrobenzyl alcohol. The microsomal oxidation of 2-aminobenzyl alcohol also resulted in the formation of two reducing agents, one of which was the corresponding hydroxylamine. The formation of 2-hydroxylamino-6-nitrobenzyl alcohol from the microsomal oxidation of 2-amino-6-nitrobenzyl alcohol was linear with respect to time for at least 20 min, while aminophenol formation was only linear for 3 min. The rate of the microsomal oxidation of 2-amino-6-nitrobenzyl alcohol was decreased by known inhibitors of cytochrome P-450, while heat inactivation of microsomal flavin containing monooxygenase had no effect. The rate of formation of both metabolites was increased 1.5-fold by phenobarbital pretreatment. Pretreatment with beta naphthoflavone had no effect on the rate of N-hydroxylation, while a small but statistically significant increase in the rate of C-hydroxylation (117% of control) was observed. The rate of oxidation of 2-amino-6-nitrobenzyl alcohol was lower with microsomes from female rats than with those from males, yielding male/female ratios of 1.34 for aminophenol formation and 3.26 for hydroxylamine formation. These data indicate that 2-amino-6-nitrobenzyl alcohol, a metabolite of the hepatocarcinogen 2,6-dinitrotoluene, can be N-hydroxylated by hepatic microsomal cytochrome P-450. The results are consistent with the hypothesis that a hydroxylamine metabolite of 2,6-dinitrotoluene is sulfated in vivo to produce an electrophilic species. PMID- 4022003 TI - Participation of a rat liver cytochrome P-450 induced by pregnenolone 16 alpha carbonitrile and other compounds in the 4-hydroxylation of mephenytoin. AB - Mephenytoin 4-hydroxylation, which has been found to be one of the reactions showing genetic polymorphism in humans, has been studied using rat liver microsomes. Pregnenolone 16 alpha-carbonitrile, dexamethasone, troleandomycin, and phenobarbital (but not beta-naphthoflavone) induced the hydroxylation activity to various extents. Mephenytoin itself also increased 4-hydroxylation considerably. Liver microsomes prepared from male rats contained higher mephenytoin hydroxylase activity than preparations isolated from females. These results suggest that a cytochrome P-450 which is inducible by pregnenolone 16 alpha-carbonitrile is involved in the 4-hydroxylation of mephenytoin. We purified cytochrome P-450PCN-E from pregnenolone 16 alpha-carbonitrile-treated rats using modifications of previous methods and compared its 4-hydroxylase activity with other purified rat cytochromes P-450. P-450PCN-E had the highest activity among the 10 purified rat cytochromes P-450 tested and antibodies raised to P-450PCN-E completely inhibited mephenytoin 4-hydroxylase in rat liver microsomes, suggesting the involvement of P-450PCN-E in this reaction. The microsomal concentration of P-450PCN-E, estimated by immunoelectrophoretic blotting analysis, correlated well with the hydroxylase activity in rat liver microsomes (r = 0.906). Mephenytoin induced P-450PCN-E as well as other phenobarbital inducible cytochromes P-450. PMID- 4022004 TI - Effect of prolactin and glucocorticoids on P-enolpyruvate carboxykinase activity in liver and mammary gland from diabetic and lactating rats. AB - The administration of 2 bromo-alpha-ergocryptine, to reduce serum prolactin decreased the activity of cytosolic P-enolpyruvate carboxykinase (GTP) (EC 4.1.1.32) about 50% in both liver and mammary gland of lactating animals. Adrenalectomy had similar effects to those of bromo-alpha-ergocryptine. In contrast, there was a 50% increase in enzyme activity in the mammary gland of diabetic, lactating rats and a 10-fold increase in liver as compared with normal rats. P-enolpyruvate carboxykinase activity in mammary gland as liver is coordinately regulated by prolactin, glucocorticoids and insulin. PMID- 4022005 TI - The role of the cell cycle in differentiation of the cellular slime mould Dictyostelium discoideum. AB - During development and differentiation of the cellular slime mould Dictyostelium discoideum there appears to be a relationship between the cell cycle and cell fate: amoebae halted in G2 phase during early development differentiate into spores whereas stalk cells are formed from amoebae halted in G1 phase. It is proposed that this is because a major effect of the cell cycle is to generate heterogeneity in the cell surface properties of the developing amoebae. PMID- 4022006 TI - Identification and isolation of the primary aggregation factor from the cell membrane of the sponge Geodia cydonium. AB - The primary aggregation factor (pAF) of sponge cells is a glycoprotein that is firmly associated with the cell membrane. Polyspecific antibodies (anti-GM) prepared from sera raised against membranes of cells from the siliceous sponge Geodia cydonium were found to inhibit initial aggregation of homologous cells. The inhibition of aggregation, caused by anti-GM was neutralized by pAF. The pAF had been successfully solubilized and enriched by affinity chromatography, gel filtration and density gradient centrifugation, if checked by polyacrylamide gel electrophoresis in the presence of urea. The Mr of the native pAF was approximately 40 000 as estimated by gel filtration; under denaturing conditions three protein species (Mr: 16 500, 15 500 and 13 500) were identified in the pAF preparation. The pAF was precipitable by Ca++ and did not cross-react with antisera against homologous purified secondary aggregation factor and lectin. It is mainly composed of protein (48.0%) and carbohydrate (50.2%). The isolated pAF restored the aggregation potency not only of factor-depleted Geodia cells but also of cells from other Demospongiae. However, the pAF displayed no aggregation enhancing effect on urea-treated cells from species belonging to the Calcispongiae or Hexactinellida. We hypothesize that in contrast to the secondary aggregation, the initial aggregation of Geodia cells is mediated by the one component system, the bivalent and bifunctional pAF. PMID- 4022007 TI - Eucaryotic transcription complexes are specifically associated in large sedimentable structures: rapid isolation of polymerase I, II, and III transcription factors. AB - RNA synthesis in eucaryotes takes place on template molecules that are activated by stably associating with limiting transcription factors. In this paper we demonstrate that such stable transcription complexes can be specifically sedimented from in vitro transcription reaction mixtures by mild centrifugation. This occurs with stable complexes of genes transcribed by all three classes of eucaryotic RNA polymerase and with S-100 as well as whole-cell extracts. However, the transcriptional capacity of the isolated complex differs for the three polymerase classes. The pelleted ribosomal DNA (polymerase I) complex contains all the factors necessary for transcription, each purified 25- to 50-fold, whereas the pelleted adenovirus major late promoter (polymerase II) complex lacks a factor that remains in the supernatant. In the case of 5S DNA (polymerase III), a necessary factor associates slowly with the sedimentable complex. Notably, the interactions responsible for this rapid sedimentation are specific for DNA molecules in stable complexes, suggesting that the in vitro sedimentable complex mirrors the in vivo structural organization of active genes. PMID- 4022008 TI - The 45-kb unit of major urinary protein gene organization is a gigantic imperfect palindrome. AB - The multigene family which codes for the mouse major urinary proteins consists of about 35 genes. Most of these are members of two distinct groups, group 1 and group 2. The group 1 and group 2 genes are organized in head-to-head pairs within 12 to 15 remarkably uniform chromosomal units or domains about 45 kilobase pairs (kb) in size. The 45-kb units are located on chromosome 4, and many of them are adjacent to each other. We propose that the 45-kb unit is a unit both of organization and of evolutionary change. In this study the homologies within the unit were observed by examining, in an electron microscope, heteroduplex and foldback structures made from cloned major urinary protein genes. These show that the 45-kb unit is a gigantic imperfect palindrome. Each arm of the palindrome contains two regions of inverted symmetry of 9.5 and 4.5 kb separated by a 3-kb nonsymmetrical region. We argue that the nonsymmetrical regions arose by a series of deletion events in the two arms of the palindrome. The center of the 45-kb unit is an 8-kb sequence without inverted symmetry flanked by the 9.5-kb regions, which contain the 4-kb genes and their immediate 5' and 3' flanking regions. The junction between adjacent 45-kb units is a 2- to 4-kb sequence without inverted symmetry flanked by the 4.5-kb regions. Some of the 45-kb units are arranged as direct tandem repeats. Others appear to be in inverted orientation with respect to a neighboring unit. Cloned major urinary protein genes show few incidences of the repetitive elements B1, B2, R, and MIF. Two elements, a B1 and an R, may be a constant feature of the 45-kb units. If so, in those cases in which the units are in tandem array, both of these elements will occur with a 45-kb periodicity. A comparison of corresponding parts of different 45-kb units shows that they differ because of a number of deletion or insertion events, particularly in the regions 3' to the genes. PMID- 4022009 TI - Reconstruction of appropriate tubulin and actin gene regulation after transient transfection of cloned beta-tubulin and beta-actin genes. AB - Most animal cells rapidly depress the synthesis of new alpha- and beta-tubulin polypeptides in response to microtubule inhibitors that increase the pool of depolymerized subunits. This apparent autoregulatory control of tubulin synthesis is achieved through the modulation of tubulin mRNA levels. To begin to analyze the molecular mechanism responsible for such regulation, we have introduced exogenous beta-tubulin gene sequences into cultured mouse cells by DEAE-dextran mediated DNA transfection. We find that the heterologous tubulin genes are expressed and that their RNA transcripts are accurately processed to mature mRNAs. Moreover, after drug-induced microtubule depolymerization, the expression of unintegrated tubulin gene sequences is regulated coordinately with the endogenous mouse alpha- and beta-tubulin RNA transcripts. Such regulation appears to be specific for transfected tubulin genes, since similar down-regulation is not observed in a contransfected beta-actin gene. Curiously, in response to microtubule depolymerization, the amount of RNA transcripts from a transfected beta-actin gene increases twofold, which qualitatively and quantitatively parallels that seen by the RNAs encoded by the endogenous actin genes. Thus, the transient DNA transfection approach may permit the unambiguous elucidation of regulatory sequences involved in establishing the proper level of expression of these two important cytoskeletal gene families. PMID- 4022010 TI - Mouse testes contain two size classes of actin mRNA that are differentially expressed during spermatogenesis. AB - Using several actin isotype-specific cDNA probes, we found actin mRNA of two size classes, 2.1 and 1.5 kilobases (kb), in extracts of polyadenylated and nonpolyadenylated RNA from sexually mature CD-1 mouse testes. Although the 2.1-kb sequence was present in both meiotic and postmeiotic testicular cell types, it decreased manyfold in late haploid cells. The 1.5-kb actin sequence was not detectable in meiotic pachytene spermatocytes (or in liver or kidney cells), but was present in round and elongating spermatids and residual bodies. To differentiate between the beta- and gamma-actin mRNAs, we isolated a cDNA, pMGA, containing the 3' untranslated region of a mouse cytoplasmic actin that has homology to the 3' untranslated region of a human gamma-actin cDNA but not to the 3' untranslated regions of human alpha-, beta-, or cardiac actins. Dot blot hybridizations with pMGA detected high levels of presumptive gamma-actin mRNA in pachytene spermatocytes and round spermatids, with lower amounts found in elongating spermatids. Hybridization with the 3' untranslated region of a rat beta-actin probe revealed that round spermatids contained higher levels of beta actin mRNA than did pachytene spermatocytes or residual bodies. Both probes hybridized to the 2.1-kb actin mRNA but failed to hybridize to the 1.5-kb mRNA. PMID- 4022012 TI - Nonexpression of a major heat shock gene in mouse plasmacytoma MPC-11. AB - The major heat shock gene coding for a 68,000-dalton protein was found to be silent in mouse plasmacytoma MPC-11 in both control and stressed cells. The block appears to be at the level of transcription, although RNA processing or instability has not been ruled out. It is not caused by a major deletion or rearrangement of the gene. PMID- 4022011 TI - Characterization of the functional gene and several processed pseudogenes in the human triosephosphate isomerase gene family. AB - The functional gene and three intronless pseudogenes for human triosephosphate isomerase were isolated from a recombinant DNA library and characterized in detail. The functional gene spans 3.5 kilobase pairs and is split into seven exons. Its promoter contains putative TATA and CCAAT boxes and is extremely rich in G and C residues (76%). The pseudogenes share a high degree of homology with the functional gene but contain mutations that preclude the synthesis of an active triosephosphate isomerase enzyme. Sequence divergence calculations indicate that these pseudogenes arose approximately 18 million years ago. We present evidence that there is a single functional gene in the human triosephosphate isomerase gene family. PMID- 4022013 TI - Haploid expression of a unique c-abl transcript in the mouse male germ line. AB - RNA from immature mouse testes was shown to lack a low-molecular-weight c-abl transcript previously noted to be the predominant species in adult testes. The developmental pattern of appearance of this c-abl variant was determined by analyzing RNA obtained from purified populations of testicular cells in different stages of spermatogenesis. The appearance of the c-abl testicular variant was coincident with the entry of the germ cells into their haploid state and suggested that the regulated expression of this proto-oncogene may be important in the normal differentiation of the male germ line. PMID- 4022014 TI - Further evidence showing that neurotoxin-acetylcholine receptor dissociation is accelerated by monoclonal neurotoxin-specific immunoglobulin. AB - We have demonstrated that the dissociation of Naja nigricollis alpha-toxin from the two acetylcholine receptor sites [Weber and Changeux, Molec. Pharmac. 10, 1 14 (1974); Rousselet et al., Eur. J. Biochem. 140, 31-37 (1984)], is markedly accelerated by a monoclonal neurotoxin-specific antibody. The dissociation of the toxin occurs in a biphasic manner in the presence of a 900 molar excess of immunoglobulin (with respect to toxin concn). The progress curves are characterized by first-order kinetics. Under these conditions the maximal dissociation rate is achieved as further rate enhancement cannot be induced by exposure to an increased immunoglobulin level. In contrast when a toxin immunoglobulin complex is incubated with a large excess of receptor, the dissociation kinetics of the complex are not enhanced. The data fit a kinetic model which implicates the existence of a transient ternary complex involving the receptor, the toxin and the antibody. PMID- 4022015 TI - Conditions for binding bovine IgG1 to protein A-Sepharose. AB - Conditions were established so that both subclasses of bovine IgG were bound to Protein A-Sepharose. Increasing the pH of the starting buffer to pH 8.0 from pH 7.0 and increasing the starting phosphate concentration of the buffer to 0.5 M from 0.2 M enhanced the separation. Using these modifications in the buffer system, IgG1 was eluted from pH 7.0 to 7.8 and IgG2 at pH 5.0. Two major peaks were associated with IgG1 activity indicating heterogeneity of binding to protein A-Sepharose. One peak was found for IgG2. The molecular weights of the fractions were determined to be that of IgG by sodium dodecyl sulfate polyacrylamide gel electrophoresis. PMID- 4022016 TI - Structural features of the autoantigens involved in thyroid autoimmune disease: the thyroid microsomal/microvillar antigen. AB - The microsomal/microvillar antigen of the human thyroid gland which provokes thyroid autoimmunity was characterised by immunoprecipitation studies. Sera from patients with Hashimoto's thyroiditis, primary myxoedema or Graves' disease containing autoanti-microsomal antibody specifically precipitated a component, which under reducing conditions migrates with a mol. wt of 105,000 on SDS polyacrylamide gel electrophoresis. This protein was absent in auto- or xeno-anti thyroglobulin precipitates, which under reducing conditions display four polypeptides of Mr 260,000, 230,000, 180,000 and 142,000. Under non-reducing conditions, the microsomal/microvillar antigen displayed a small shift in mobility to a mol. wt of 117,000 suggesting the presence of intrachain disulphide bonds. In contrast, under these conditions, anti-thyroglobulin precipitated components displaying polypeptides of approx. mol. wts in the region of 240,000 260,000, 170,000-180,000 and 140,000. Absorption of thyroiditis sera on thyroglobulin-Sepharose followed by immunoprecipitation abolished the anti thyroglobulin components without affecting the binding of the 105,000-dalton polypeptide, if the sera contained antimicrosomal antibody. No comparable material was identified in microsomal membrane preparations prepared from the stomach which is also commonly involved in organ-specific autoimmunity. The 105,000-dalton component does not bind to a Lens culinaris lectin affinity column. We conclude that the epitopes of the microsomal/microvillar antigen are presented on a poorly glycosylated peptide of mol. wt 105,000, which is probably stabilised by intrachain disulphide bonds and which does not share serological reactivity with membrane-bound thyroglobulin. PMID- 4022017 TI - Affinity chromatographic purification of antibody subsets depends on the mode of cross-linking of antigen to the affinity matrix. AB - Affinity columns for the separation of rabbit antibodies (Abs) to the purified nicotinic acetylcholine receptor (AcChR) from Torpedo californica electroplax were constructed in two ways: (1) by direct cross-linking of purified AcChR to cyanogen bromide activated Sepharose 4B, and (2) by first cross-linking a purified curarimimetic neurotoxin to cyanogen bromide activated Sepharose 4B, subsequently saturating with AcChR, and finally cross-linking the toxin to noncovalently bound receptors with bisimidate cross-linkers such as dimethyl suberimidate (DMS). Ab(AcChR) from pooled rabbit antisera were chromatographed in near stoichiometric proportions to the AcChR bound to the column to allow equilibrium selection of antibodies directed against sites which were not sterically hindered. The concept that columns of the second type subfractionate Ab(AcChR) was tested by analyzing Ab(AcChR) from column fractions with an ELISA and radioimmunoassay (RIA) procedure. The ELISA was constructed to that the exposed face of the AcChR was the same as that expected for columns of the second type, i.e. for the internal or cytoplasmic face. Enhanced ratios of ELISA to RIA measures of Ab(AcChR) reflected substantial purification of cytoplasmic face antibodies in DMS-cross linked columns. Total Ab(AcChR) was measured by RIA. Both types of columns gave substantial purification of tightly bound antibodies, i.e. those which were eluted with 3M potassium thiocyanate. Thirty-fifty percent of the IgG eluted was found in these fractions, which contained 2-6% of the total eluted protein. Approximately half of the total IgG present in these fractions represented specific IgG against AcChR. Both types of columns could be reutilized giving similar results; however, their efficiency was diminished. PMID- 4022018 TI - Fc intermediate (Fci), a papain-generated fragment of human IgG, intermediate in charge, molecular weight and cleavage between the Fc and Fc' fragments of IgG. AB - Fc intermediate (Fci) is a papain-generated fragment of human IgG which is intermediate in charge, mol. wt and state of cleavage between the Fc and Fc' fragments of IgG. It is composed of two polypeptide chains of unequal mol. wt held together by non-covalent bonds between the C gamma 3 regions. The larger polypeptide chain has both a C gamma 2 and C gamma 3 domain and its N-terminus is at Leu 235 (60%) and Leu 234 (40%) (IgGl Eu numbering). The smaller polypeptide chain is composed of a C gamma 3 domain with its N-terminus at Gly 341. The carboxy-termini obtained by carboxypeptidase digestion and by a computer program which determined the most probable sequences by fitting the amino acid compositions to the sequence of IgG Eu Fc were heterogeneous involving residues 440-446 for the large polypeptide chain and 429-436 for the small one. The calculated mol. wt of the large polypeptide chain was 26,183, assuming the N terminus at Leu 234 and C-terminus at 446 and including the carbohydrate moiety. The calculated mol. wt for the small polypeptide chain was 10,682, with the N terminus at 341 and assuming the C-terminus at 434, for a combined mol. wt of 36,865 for the Fci fragment. Sedimentation equilibrium ultracentrifugation of Fci under non-dissociating conditions showed an Mn of 36,200 +/- 1200, an Mw of 36,400 +/- 600 and an Mz of 37,000 +/- 300 g/mole. The best yields of Fc were obtained with a 6-hr digestion and the best yields of Fcl and Fc' were obtained with digestion for 18 hr in phosphate buffer. Digestion in Tris buffer for 18 hr gave results similar to the 18-hr digestion in phosphate buffer except the yields of Fc' were less. This fragment may be useful for exploring biological functions of human IgG Fc. In addition, some Fc fragments obtained by papain digestion of human IgG either in phosphate or Tris buffer are not covalently bonded and are probably cleaved on the carboxy-terminal side of the interchain disulfide bonds at Leu 234 or Leu 235, the N-termini for the large polypeptide chain of Fci. This indicates that, if disulfide bonded Fc fragments are needed, gel filtration under dissociating conditions will be necessary to remove non-covalently bonded Fc. PMID- 4022019 TI - [Ontogenesis of lymphoid organs. Immunophenotype and tissue structure]. PMID- 4022021 TI - [Molecular interactions in fluorescence polarization analysis]. PMID- 4022020 TI - [Portal hypertension of non-cirrhotic origin]. PMID- 4022022 TI - [Fulminating fatal dermatomyositis and myasthenia gravis after a bee sting (clinicopathological study)]. PMID- 4022023 TI - Fecal mutagenicity arising from ingestion of fried ground beef in the human. AB - Fried ground beef has been shown to contain mutagens, and the major mutagenic component has been identified as 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx). Mutagens in feces of 3 adult volunteers were fractionated by treatment of the feces with blue cotton followed by chromatography on a carboxymethyl cellulose column. The chromatographic fraction, corresponding to MeIQx in terms of the position of elution, was examined for mutagenicity in S. typhimurium TA98 with metabolic activation. When meals containing no heated meat were eaten, this fraction of feces showed little or no mutagenicity. On eating fried ground beef, the feces excreted in the next two days showed greatly increased mutagenicity in this fraction. By eating no-meat meal subsequent to the meat meal, the mutagenicity resumed the original low level on the fourth day after the meat meal. The components in the mutagenic fraction were probably metabolites of the mutagens present in cooked meat, since analysis by high pressure liquid chromatography of the mutagenic fraction showed that the active components in the feces were different from the mutagens in cooked meat. PMID- 4022024 TI - A preliminary analysis of the genotoxicity of a few spices in Drosophila. PMID- 4022025 TI - Sister-chromatid exchanges and chromosomal aberrations in a population exposed to pesticides. AB - Sister-chromatid exchanges (SCE) and chromosomal aberrations were studied in a population of floriculturists occupationally exposed to organophosphorus, carbamate and organochlorine pesticides. Blood samples from 36 individuals from a community of 154 persons of asiatic origin were obtained. Among the group sampled, 21 individuals exhibited at least one symptom of chronic intoxication. SCE analysis was performed in 14 symptomatic and 13 asymptomatic persons. The asymptomatic group showed a SCE frequency of 5.47 +/- 1.03 and the symptomatic group a frequency of 6.45 +/- 1.19. Comparison between both groups with the Mann Whitney 'U' test revealed a significant difference (p 0.0409). Case-control analysis of 9 pairs matched by sex and age also showed significant differences between both groups (p 0.0104). In contrast, the frequencies of chromosomal aberrations were not correlated with intoxication symptomatology, though a significant increment of exchange-type aberrations in relation to a group of non floriculturists was observed in the population studied. PMID- 4022026 TI - A study of the frequency of sister-chromatid exchange and of thioguanine resistant cells in mouse spleen lymphocytes after in vivo exposure to ethylnitrosourea. AB - As part of the development of a multi-endpoint, in vivo, mouse model for mutagenesis we have measured the frequency of sister-chromatid exchange (SCE) and the frequency of thioguanine-resistant (TGr) cells among the lymphocytes of the mouse spleen following acute, intraperitoneal exposure to ethylnitrosourea (ENU). The responses of these two endpoints have been monitored both as a function of the dose of ENU injected, ranging from 0 to 70 mg/kg, and as a function of time after injection, from 1 day to 72 days. The SCE frequency response was highest 1 day after the ENU was injected, increasing 2.5-fold over control values for mice that received 70 mg/kg, and declined to control values in all animals by 72 days. SCE showed a linear dose response both at 1 day and 8 days after injection. The frequency of TGr cells was at control levels at 1 day, but at 15, 36 and 72 days after ENU injection the frequency of TGr cells showed a linear dose response. In addition, the frequency of TGr cells increased linearly with time for both the 35 and 70 mg/kg doses. The frequency of TGr cells for mice that had received 70 mg ENU/kg 72 days previously, was 100-fold higher than in control animals, giving a frequency of 1.4 X 10(-4). PMID- 4022027 TI - The effect of caffeine on X-ray-induced mitotic delay in normal human and ataxia telangiectasia fibroblasts. AB - We previously showed that radiation-sensitive fibroblasts from ataxia telangiectasia (A-T) patients sustain less G2 delay after X-irradiation than normal fibroblasts (Scott and Zampetti-Bosseler, 1982). Caffeine is known to reduce the amount of X-ray-induced delay in various mammalian cell types. Painter and Young (1980) proposed that A-T cells have an altered chromatin structure, similar to that of caffeine-treated normal cells and that this results in a failure of A-T cells to delay their progression through the cell cycle to allow time for DNA repair. We now show that caffeine treatment after X-irradiation reduces G2 delay in both A-T and normal cells. We confirm the results previously obtained on lymphocytes that caffeine potentiates the chromosome-damaging effects of X-rays in both A-T and normal fibroblasts. These and other data suggest that the radiation responses of A-T cells and of caffeine-treated normal cells are caused by different mechanisms. PMID- 4022028 TI - Cytostatic drug activity in plasma, a bioassay for detecting mutagenicity of directly and indirectly acting chemicals, an evaluation of 20 chemicals. AB - We have utilized in vivo drug metabolism for detecting the mutagenicity of known indirectly-acting chemical mutagens. Exponentially growing Chinese hamster ovary (CHO) cells were incubated with plasma derived from treated rats containing active metabolites of the test chemicals. The genotoxicity was assessed by the 18 of tested chemical mutagens. Plasma from rats treated with known non-mutagens did not increase the frequencies of SCEs. The results indicate that this method could be useful for the demonstration of genotoxicity of chemicals which need metabolic activation to be effective, and especially those which are not effective, when in vitro activation conditions (S9 mixture) are used. PMID- 4022029 TI - Effect of environmental factors on induced chromosomal aberrations in newborns. AB - Repeated blood collection was performed in newborns living in 3 distinct areas of the country with different levels of chemical pollution in the environment. Both the classical and SCE techniques were used in parallel. Blood samples from mothers and 1-year-old infants in the same area were also analysed to compare age dependent sensitivity to mutagens. Cells with classical aberrations increased significantly according to higher chemical pollution, the levels of SCEs were not significantly changed. No age-dependent difference in sensitivity to chemical mutagens was found. PMID- 4022030 TI - Cluster analysis of short-term tests: a new methodological approach. AB - A totally data-based approach to the evaluation of short-term tests is proposed. The performances of 22 tests over a range of 42 chemicals (data from literature) were studied by cluster analysis. The comparison between them was performed only on the basis of their responses to the chemicals. Two different clustering methods produced a coincident classification, pointing to a clear resolution of all tests into 3 groups with common characteristics. With respect to carcinogen discrimination, cluster 1 showed the highest sensitivity and the lowest specificity. Cluster 3 had opposite characteristics. The tests of cluster 2 showed intermediate features. As far as the membership to clusters is concerned, the literature data about the responses to chemicals indicated a strong test system specificity. This apparently overcame both phylogeny and end-point community. A major characteristic of the present approach is the ability to elicit underlying patterns, the knowledge of which can contribute both to hypothesis formulation and be useful for practical purposes. PMID- 4022031 TI - High-pressure liquid chromatography for isolation of clastogenic agents from urine. AB - Small columns of XAD-2 resin have been widely used to extract and concentrate mutagenic materials from urine. Using analytical HPLC and assays for clastogenicity with Chinese hamster ovary cells, we found that small columns of XAD-2 resin (1.5 ml bed volume) retain only a small percentage of organic material and undetectable amounts of genotoxic activity in urine samples. Increasing the size of the XAD resin bed resulted in better recoveries, but much organic material was still lost by overloading of the column. In contrast, when urine was acidified and chromatographed by preparative reversed-phase HPLC using large-bed-volume (500 ml) commercial columns, retention of hydrophobic organic material from urine was excellent. Subsequent stepwise elution of the column with increasing concentrations of acetone produce 3 fractions of organic material of increasing hydrophobicity. When urine from smokers was analysed, all 3 fractions contained material which was clastogenic to Chinese hamster ovary cells. The procedures developed are suggested as a new general purpose approach to the isolation of genotoxic materials from urine. PMID- 4022032 TI - Clastogenic agents in the urine of coffee drinkers and cigarette smokers. AB - Organic material from the urine of smokers, coffee drinkers, and controls was extracted and separated into 3 fractions of differing hydrophobicity using preparative reversed-phase high-pressure liquid chromatography. Fractions were assayed for clastogenic activity using Chinese hamster ovary cells. Smoking, coffee drinking, or both habits together resulted in a substantial increase in the genotoxicity of organic material in all 3 fractions. The clastogenicity of fractions 1 and 2 (the two most hydrophilic) was abolished by the addition of either catalase or superoxide dismutase to the Chinese hamster ovary cell system, suggesting the involvement of active oxygen species in the clastogenic response. Clastogenicity of fraction 3, however, was resistant to the action of catalase and superoxide dismutase. Fractions were tested for their ability to generate hydrogen peroxide in vitro during a 10-min incubation at elevated pH. Fractions 2 and 3, but not fraction 1 from smokers, coffee drinkers, or those with both habits generated significantly more hydrogen peroxide at high pH than did the corresponding fractions from control subjects. For fractions 2 and 3 but not 1, the ability of a sample to generate hydrogen peroxide at high pH was positively correlated with its ability to generate chromosome aberrations at neutral pH in tissue culture. The data indicate that both coffee drinking and cigarette smoking result in the appearance of clastogenic materials in urine, and suggest that such clastogenic agents may produce chromosome aberrations via the production of active oxygen species. PMID- 4022033 TI - Abnormal development and transport and increased sister-chromatid exchange in preimplantation embryos following superovulation in mice. AB - Both sister-chromatid exchange (SCE) response and embryonic development and transport in preimplantation embryos were evaluated on day 3 of gestation (vaginal plug = 1) of superovulated Swiss mice. Superovulation was found to have significant effects on number of preimplantation embryos (increase), embryo localization (accelerated transport), cleavage rate (advanced development) and abnormality rate (misshaped, fragmented, dead embryos). Superovulated 4- and 8 cell embryos collected from oviducts and uteri and incubated in vitro with 5 bromodeoxyuridine (BrdU) displayed up to 4 times higher SCE frequency than spontaneously ovulated embryos. This increase is independent of stage of development and location at the time of embryo collection. The results indicate that superovulated embryos may have induced DNA lesions. PMID- 4022034 TI - Personal comments on 'Environmental Protection Agency' proposed guidelines for mutagenicity risk assessment. PMID- 4022035 TI - Dose-related chromosome non-disjunction in female mice after X-irradiation of dictyate oocytes. AB - The chromosome non-disjunction inducing effect of relatively large doses (100-600 cGy) of X-rays to various dictyate oocyte stages has been examined by chromosomal analysis of 1-cell embryos recovered from female mice 3.5-23.5 days after irradiation. Numerical chromosome anomalies, as a result of non-disjunction, occurred in significantly larger proportions of embryos from irradiated females compared to unirradiated controls. Moreover, non-disjunction was induced by X irradiation in dose-related fashions which could be described by either quadratic or dose-squared curves. The different oocyte maturation stages sampled showed significantly different responses to X-irradiation. The most mature stage, sampled 3.5 days after treatment, was less responsive to the non-disjunction inducing effect of X-rays compared to other, younger maturation stages. Chromosome structural anomalies were also found significantly more frequently after X-irradiation of dictyate oocytes. Structural anomalies were induced in dose-related fashions in all oocyte maturation stages and could be described by either quadratic or dose-squared curves. A smaller proportion of embryos from females sampled at the shortest interval after irradiation contained structural anomalies compared to those from females sampled at the longer intervals. No evidence was obtained for a significant effect of X-irradiation on the frequency of triploid embryos. PMID- 4022036 TI - Dose-response relationship of gamma-ray-induced reciprocal translocations at low doses in spermatogonia of the crab-eating monkey (Macaca fascicularis). AB - The yield of translocations induced by acute gamma-irradiation at low doses (0.25 and 0.50 Gy) in the crab-eating monkey's (Macaca fascicularis) spermatogonia was examined. The frequencies of translocations per cell were 0.53% at 0.25 Gy and 1.07% at 0.50 Gy. Over the low dose range from 0 to 1 Gy, the dose-response relationship for translocation yield was a linear one with a regression coefficient of 1.79 X 10(-2). To estimate the sensitivity to the induction of translocations in the crab-eating monkey's spermatogonia, the slope of the regression line was compared with those in other mammalian species. Consequently, over the low dose range below 1 Gy, the sensitivity of the crab-eating monkey's spermatogonia to translocation induction was similar to several mammalian species, the mouse. Chinese hamster, and the rabbit, but significantly higher than that of the rhesus monkey and lower than that of the marmoset. PMID- 4022037 TI - DNA damage induced by nitropyrenes in primary mouse hepatocytes and in rat H4-II E hepatoma cells. AB - The capacity of nitropyrenes to cause DNA damage in primary mouse hepatocytes (C57BL/6N mice) and rat H4-II-E hepatoma cells was studied by estimating single strand breaks using the alkaline elution technique. 1-Nitropyrene (10-200 microM) caused clear dose-dependent increases in DNA strand breaks in both cell types, whereas no increase in DNA strand breaks was observed in hepatocytes treated with 1.3-, 1,6-, 1,8-dinitropyrene, 1,3,6-trinitropyrene and 1,3,6,8-tetranitropyrene under standard assay conditions (5-20 microM 30-min incubation). However, 1,8 dinitropyrene (1,8-DNP) caused dose-dependent increases in DNA strand breaks when incubated with the H4-II-E cells for 48 h, while no single-strand breaks were observed following treatment with 1,6-dinitropyrene (1,6-DNP) under the same conditions. Neither 1,6-DNP nor 1,8-DNAP induced DNA crosslinks in the H4-II-E cells. These data indicate that substrate specificity exists in the metabolic activation of nitropyrenes in murine liver. PMID- 4022038 TI - Chromatid damage induced by fluorescent light during G2 phase in normal and Gardner syndrome fibroblasts. Interpretation in terms of deficient DNA repair. AB - Skin fibroblasts from Gardner syndrome (GS) compared with those from normal donors showed a significantly higher incidence of chromatid gaps and breaks following exposure to low-intensity, cool-white fluorescent light during G2 phase of the cell cycle. Considerable evidence supports the concept that chromatid gaps and breaks seen directly after exposure to DNA-damaging agents represent unrepaired DNA single- and double-strand breaks respectively. The changes in incidence of chromatid aberrations with time after light exposure are consistent with the sequence of events known to follow DNA damage and repair. Initially, the incidence of light-induced chromatid gaps was equivalent in GS and normal fibroblasts. In the normal cells, the chromatid gaps disappeared by 1 h post exposure, presumably as a result of efficient repair of DNA single-strand breaks. In contrast, the incidence of gaps increased in GS cells by 0.5 h followed by a decrease at 1 h and concomitant increase in chromatid breaks. It appears from these findings that the increased incidence of chromatid damage in GS fibroblasts results from deficient repair of DNA single-strand breaks which arise from incomplete nucleotide excision of DNA damage during G2 phase. PMID- 4022039 TI - Cytosine arabinoside is a potent clastogen and does not affect the repair of X ray-induced chromosome fragments in unstimulated human lymphocytes. AB - The metabolic inhibitor of DNA synthesis cytosine arabinoside (ara-C) is known to induce chromosome aberrations in human lymphocytes. It has been recently argued, however, that there is no unequivocal evidence that ara-C can damage chromosomes directly. Therefore, the effect of ara-C on unstimulated human lymphocytes was examined directly by means of the premature chromosome condensation technique. In about 50% of the cells, ara-C effectively induced chromosome fragments, which did not show rejoining even after the chemical was washed out. These results suggest that a possible selection against damaged cells in their progress to mitosis could result in the low yields of ara-C-induced chromosome aberrations reported in the literature. The effect of ara-C on the repair of radiation-induced chromosome aberrations was also examined. Ara-C did not affect the rejoining of the chromosome fragments induced in unstimulated human lymphocytes by 6 Gy of X rays. PMID- 4022040 TI - Gamma-rays kill grasshopper primary spermatocytes in groups. AB - Primary spermatocyte killing by gamma-rays was studied in the grasshopper Heteracris littoralis in which spermatogenic development occurs in cysts containing a maximum of 64 cells during the first meiotic division. Cell killing at this stage is not random and mainly involves the death of whole cysts. The dose-response curve for cell killing has complex kinetics with at least two components but lacks any shoulder at low doses, thus indicating no repair of the lethal damage. Cell loss is apparent from surviving cysts as early as 45 min post irradiation but loss of greater than 24 cells is incompatible with cyst survival. Loss of fewer than 24 cells also is not random since certain values for cell loss are frequently observed while other, interspersed values are not seen at all. PMID- 4022041 TI - In vitro studies of biological effects of cigarette smoke condensate. I. Genotoxic and cytotoxic effects of neutral, semivolatile constituents. AB - Much of the biological activity of cigarette smoke resides in the neutral fraction of the particulate phase. Since the volatile constituents of this material, the semivolatiles, are accessible to selective filtration, some of the biological activity of cigarette smoke might be reduced. In view of this, the genotoxic and cytotoxic effects and the chemical composition of the semivolatile neutral material of a cigarette smoke condensate was investigated. Cigarette smoke condensate obtained from domestic American blend type cigarettes, was separated into a volatile, a nonvolatile and a semivolatile fraction. The semivolatile constituents were fractionated by liquid-liquid extraction into 4 subfractions: acids, phenols, bases and neutrals. The neutral material was separated further by silica gel chromatography into 7 subfractions of varying polarity. The major components of these were identified by gas chromatography mass spectrometry. These fractions were studied using 4 in vitro short-term tests, of which 2, the Ames test and induction of sister-chromatid exchanges, provided information on their genotoxicity and the other 2 provided information on their cytotoxicity by measuring inhibition of cell growth and inhibition of oxidative metabolism. Sister-chromatid exchanges were induced by the neutral fraction and the 7 subfractions, the activities of which increased with increasing polarity. Neither the total neutral material, nor the subfractions showed any mutagenic activity in the Ames test. The cytotoxic effect of the fractions of medium polarity, was greater than that of the total neutral material, while the most and the least polar fractions were less toxic. PMID- 4022042 TI - The mutagenic potency of 4 agents at the thymidine kinase locus in mouse lymphoma L5178Y cells in vitro: effects of exposure time. AB - Mutagenic potency at the thymidine kinase (TK) locus in mouse lymphoma L5178Y cells (expressed as induced trifluorothymidine (TFT)-resistant mutants/total dose) was assessed for 4 agents (ethyl methanesulphonate (EMS), benzidine, 1,8 dinitropyrene (1,8-DNP) and ICRF 159) using short (3-4 h) and long (21-24 h) exposure times. The mutagenic potency of EMS was found to be essentially independent of concentration and exposure time when tested over a cytotoxic range consistent with routine testing procedures. Similar results were obtained with benzidine but for both 1,8-DNP and ICRF 159 mutagenic potency was found to be highly dependent on the concentration and exposure time. 1,8-DNP failed to induce any significant increases in mutant frequency when tested at concentrations up to 5 micrograms/ml using short exposure times, whereas the compound was active at concentrations as low as 0.1 microgram/ml when the exposure period was extended to 21 h. Under the latter conditions, however, the molar potency of 1,8-DNP was found to be inversely related to concentration over a range extending from 0.1 to 5 micrograms/ml. ICRF 159 induced increases in the frequency of TFT-resistant mutants using short or long exposure times. When a short exposure time was used, however, the mutagenic potency of the antitumour agent decreased with increasing concentration between 1 and 500 micrograms/ml. Although possible explanations can be offered to account for these observations the results illustrate potential problems which may arise in this system when comparing mutagenic potency values for a range of compounds with a view to assessing relative risk. PMID- 4022043 TI - Comparative in vitro cytogenetic studies in mercury-exposed human lymphocytes. AB - As part of a long-term cytogenetic research project on mercury, we studied the in vitro clastogenic capacity of HgCl2 and CH3HgCl as well as their influence on chromosome segregation by means of a computer-aided chromosome distribution study in metaphase plates. As in other in vitro studies published elsewhere, we exposed human peripheral blood lymphocytes to different concentrations of the mercury compound during a limited period of the pre-DNA synthetic stage (G1-S) or from that stage up to mitosis (G1-M). For both exposure periods and both mercury compounds we observed a rather important clastogenic effect as well as a dissociation of the (normally highly associated) acrocentrics. The results do indicate, in conjunction with previously published data, that mercury compounds alter the chromosome segregation at lower concentrations than those observed for clastogenicity. Moreover, the effects on chromosome segregation are not necessarily due to binding to spindle proteins. Binding to--and inactivation of RNA polymerase I may for example be another mechanism of action which is more important for the inorganic form of mercury than for the organic form. PMID- 4022044 TI - Sister-chromatid exchanges in lymphocytes and mutagenicity in urine of nurses handling cytostatic drugs. AB - Sister-chromatid exchanges (SCE) in peripheral blood lymphocytes and mutagenicity of urine (Ames test) were measured in a group of 21 nurses professionally handling antineoplastic drugs and in a group of 21 unexposed controls. No differences in SCE frequencies and in urinary mutagenic activity between exposed and unexposed groups were detected. A clear positive increase in urinary mutagenicity in the TA98 Salmonella strain was observed with increasing number of cigarettes smoked, whereas no evident influence of smoking on SCE was seen. Age, coffee and alcohol consumption did not show any detectable effect in the two tests. PMID- 4022045 TI - Cigarette smoking and the risk of endometrial cancer. AB - Because of evidence of reduced estrogen excretion in the urine of women who smoke cigarettes and evidence linking estrogen levels to the risk of cancer of the female reproductive system, we evaluated the risk of endometrial cancer in relation to cigarette use in a hospital-based case-control study of 510 women with endometrial cancer (cases) and 727 women with other cancers (controls). The rate-ratio estimate (relative risk) for current smokers as compared with women who had never smoked was 0.7 (95 per cent confidence interval, 0.5 to 1.0), and for former smokers the estimate was 0.9 (0.6 to 1.2). For women currently smoking 25 or more cigarettes per day, the rate-ratio estimate was 0.5 (0.3 to 0.8). The effect of current smoking of at least 25 cigarettes per day appeared to be confined to postmenopausal women, among whom the estimate was 0.5 (0.2 to 0.9). Among premenopausal women the estimate was 0.9 (0.4 to 2.2), but the difference between these two estimates could have been due to chance. The data suggest that women who smoke heavily may have a lower risk of endometrial cancer than nonsmokers. The present findings do not have direct public health importance since cigarettes, overall, have serious deleterious effects. However, if these results are confirmed, elucidation of the underlying mechanisms whereby smoking reduces the risk would be of interest and might be useful in the development of strategies for preventing endometrial cancer. PMID- 4022046 TI - Impaired reticuloendothelial function in patients treated with methyldopa. AB - In about 20 per cent of patients taking the antihypertensive agent methyldopa, IgG autoantibodies form against red cells, but most such patients do not have hemolysis. The reason for this is uncertain; it does not appear to be explained by known characteristics of the autoantibody. Since antibody-dependent reticuloendothelial function is an important determinant of cell clearance, we measured reticuloendothelial function in nine patients taking methyldopa. We did this by measuring the rate of clearance of radiolabeled autologous red cells sensitized with anti-D alloantibody. Five patients had a positive direct antiglobulin test, and four did not. Only one patient had laboratory evidence of hemolysis. The patients without hemolysis had significantly impaired reticuloendothelial clearance. In contrast, the patient with hemolysis did not have impaired reticuloendothelial function. This study suggests that in patients taking methyldopa who have a positive direct antiglobulin test the absence of hemolysis may be caused by an impairment in reticuloendothelial function. That the drug itself may be responsible for the impairment is suggested by the occurrence of abnormal reticuloendothelial function in patients taking the drug who have a negative direct antiglobulin test. PMID- 4022048 TI - Community-acquired pneumonia due to penicillin-resistant pneumococci. PMID- 4022047 TI - Comparison of a quantitative treadmill exercise score with standard electrocardiographic criteria in screening asymptomatic young men for coronary artery disease. AB - A computer-derived treadmill exercise score that quantifies the electrocardiographic response to exercise has been reported to have a high sensitivity (87 per cent) and specificity (92 per cent) in patients with a high prevalence of coronary artery disease. To test its accuracy in young, asymptomatic men with a low prevalence of coronary artery disease, we evaluated the responses of 377 military officers (mean age, 36.6 years) by two independent methods. According to standard electrocardiographic criteria, 45 of the subjects (12 per cent) had positive tests, whereas the treadmill exercise score indicated that only 3 (less than 1 per cent) had positive tests. Since two of these three had left ventricular hypertrophy and met only the criteria for the latter without associated coronary artery disease, the treadmill exercise score predicted that only 1 of 377 subjects would have clinically important coronary artery disease. Coronary arteriography, performed in 10 persons with the most positive scores on standard treadmill tests and the highest scores for risk factors, showed that nine subjects did not have coronary artery disease and that one had single-vessel disease (the same subject who the treadmill score predicted would have mild disease). The treadmill exercise score appears to improve the diagnostic specificity of exercise electrocardiography and may be more useful than values on standard stress tests in screening asymptomatic populations for coronary artery disease. PMID- 4022049 TI - Can not smoking be hazardous to your health? PMID- 4022051 TI - IUDs and infertility. PMID- 4022050 TI - Another perfect treadmill test? PMID- 4022052 TI - Wernicke's encephalopathy. PMID- 4022053 TI - Altered glucose metabolism in fibroblasts from patients with Alzheimer's disease. PMID- 4022055 TI - Coronary heart disease: doing the "right things". PMID- 4022054 TI - Age-related development of human natural killer cell activity. PMID- 4022056 TI - The difference between serum and plasma potassium. PMID- 4022057 TI - Salicylate-induced musical perceptions. PMID- 4022058 TI - Low doses of dopamine agonists in the long-term treatment of macroprolactinomas. AB - To evaluate the long-term effects of dopamine agonists in the treatment of macroprolactinoma, we studied prolactin levels and tumor size for 30 to 88 months (57 +/- 14, mean +/- S.D.) in 38 patients treated with bromocriptine or lisuride. Elevated prolactin levels became normal in 30 patients, and the tumor shrank in 29. After two years of treatment, we attempted to reduce the maintenance dose (5 to 20 mg of bromocriptine per day or 0.4 to 0.8 mg of lisuride per day); in 21 patients no changes in prolactin levels or tumor size were observed over 6 to 52 months with 0.625 to 10 mg of bromocriptine per day or 0.05 mg of lisuride per day. However, it was possible to withdraw the drug in only one patient. We conclude that dopamine agonists are usually effective treatments for macroprolactinoma and that after a response has been obtained, it can be maintained in many patients with a greatly reduced dose. PMID- 4022059 TI - Cocaine use in pregnancy. AB - With the increasing use of cocaine in the United States, there has been growing concern regarding its effects on the fetuses and neonates of pregnant cocaine abusers. Twenty-three cocaine-using women enrolled in a comprehensive perinatal addiction program were divided into two groups: those using cocaine only and those using cocaine plus narcotics. These two groups were compared with a group of women who had used narcotics in the past and were maintained on methadone during pregnancy, and with a group of drug-free women. All four groups were similar in maternal age, socioeconomic status, number of pregnancies, and cigarette, marijuana, and alcohol use. Their medical histories indicated that the cocaine-using women had a significantly higher rate of spontaneous abortion than the women in the other two groups. In the pregnancies under study, four cocaine using women had onset of labor with abruptio placentae immediately after intravenous self-injection of cocaine. Neonatal gestational age, birth weight, length, and head circumference were not affected by cocaine use. However, the Brazelton Neonatal Behavioral Assessment Scale revealed that infants exposed to cocaine had significant depression of interactive behavior and a poor organizational response to environmental stimuli (state organization). These preliminary observations suggest that cocaine influences the outcome of pregnancy as well as the neurologic behavior of the newborn, but a full assessment will require a larger number of pregnancies and longer follow-up. PMID- 4022060 TI - What about the patient? PMID- 4022061 TI - La maladie du petit papier. Is writing a list of symptoms a sign of an emotional disorder? PMID- 4022062 TI - Use of the initial electrocardiogram to predict in-hospital complications of acute myocardial infarction. PMID- 4022063 TI - Pentamidine and renal toxicity. PMID- 4022064 TI - More on microvascular disease of the foot in diabetes. PMID- 4022065 TI - Phenytoin absorption in adults: effect of aging. PMID- 4022067 TI - Common-sense models of health and disease. PMID- 4022066 TI - Inflammatory gastric polyps. PMID- 4022068 TI - Absorption of chloramphenicol sodium succinate after intramuscular administration in children. AB - Because it is thought that chloramphenicol is poorly absorbed after intramuscular administration, we compared blood levels of chloramphenicol after intramuscular administration with those after intravenous administration in children with a variety of diagnoses. Fifty-seven children were studied on 62 occasions while they were receiving chloramphenicol sodium succinate (25 mg of chloramphenicol per kilogram of body weight) intramuscularly every six hours. The peak level of chloramphenicol was 19.5 +/- 5.99 micrograms per milliliter (mean +/- S.D.) in 11 children after the first dose and 31.4 +/- 12.99 micrograms per milliliter in 51 children after two or more doses. The lowest peak level after intramuscular administration was 13 micrograms per milliliter, which is in the therapeutic range of 10 to 30 micrograms per milliliter. Thirteen children were studied on 17 occasions while they were receiving chloramphenicol sodium succinate (25 mg of chloramphenicol per kilogram) intravenously every six hours. The peak level of chloramphenicol was 19.4 +/- 6.37 micrograms per milliliter in eight children after the first dose and 28.2 +/- 11.09 micrograms per milliliter in nine children after two or more doses. The area under the serum level curve was not significantly different after intramuscular and intravenous administration. We conclude that chloramphenicol sodium succinate is well absorbed after intramuscular administration. This route is cheaper, it demands less staff time, and it does not carry the risks of sepsis and overhydration associated with intravenous therapy. PMID- 4022069 TI - Risk of illness after exposure to a pediatric office. AB - To determine whether well children visiting a pediatrician's office are at risk of acquiring common communicable diseases, we conducted a prospective cohort study during the winter of 1983-1984. The occurrence of respiratory or gastrointestinal illness or fever in young children in the week after a visit to a pediatric office (office group) was compared with the occurrence of these illnesses in a similar group of children (home group) not exposed to the office during the study period. One home comparison subject was matched by age and sex to each of 127 children three years of age and under who were seen for well-child care in a private pediatric office with a common waiting room. The adjusted relative risk of the development of illness during the study week for the office group as compared with the home group was 0.95 (95 per cent confidence interval, 0.66 to 1.37), indicating no effect. We conclude that exposure to a pediatric office is not an important cause of the common infections in young children that have incubation periods of a week or less. PMID- 4022070 TI - The clinical status of hypophosphatemia: an update. PMID- 4022071 TI - Type A behavior and survival after myocardial infarction. PMID- 4022072 TI - Endomyocardial biopsy in the diagnosis of myocarditis. PMID- 4022073 TI - Does age or sex influence the probability of symptoms in coronary artery disease? PMID- 4022075 TI - Food technology. PMID- 4022074 TI - Contributions of aging and estrogen deficiency to postmenopausal bone loss. PMID- 4022077 TI - Journal peer review. PMID- 4022076 TI - Cerebrotendinous xanthomatosis. PMID- 4022078 TI - Basic curricular goals in medical ethics. PMID- 4022079 TI - Long-term metabolic control with insulin pump therapy. Report of experience with 127 patients. AB - To determine the long-term efficacy of insulin-pump therapy, we analyzed trends in glycosylated hemoglobin concentrations in 127 patients with Type I diabetes using insulin pumps for periods ranging from 13 to 47 months. In the first year of pump therapy the average glycosylated hemoglobin concentration improved in 83 per cent of the patients, as compared with the value before pump therapy. Although only 11 of the 127 subjects had normal glycosylated hemoglobin values before pump therapy, 33 had a normal average value during the first full year of pump use (P = 0.0001). This favorable trend persisted for the three-year duration of the study. Seventeen of the 19 patients who subsequently discontinued insulin pump therapy had improved glycosylated hemoglobin values during the period of pump use. Eleven of the 19 patients remained available for follow-up study; the glycosylated hemoglobin concentration became worse in 7 when they returned to conventional treatment. We conclude that the improvement in metabolic control repeatedly demonstrated in short-term studies with the insulin pump can be maintained for a period of years. PMID- 4022080 TI - The role of metabolite-specific antibodies in nomifensine-dependent immune hemolytic anemia. AB - Nomifensine is an antidepressant drug (widely used in Europe, but not yet available in the United States), which has been linked to intravascular hemolysis. We studied 19 patients (18 women and 1 man) with acute intravascular hemolysis due to nomifensine-dependent antibodies. Transitory renal insufficiency developed in at least seven patients, and four required temporary dialysis. To investigate the antibodies, we used nomifensine, its three main metabolites, and its ex vivo antigens (urine samples from a volunteer collected 1.5 to 16 hours after the ingestion of 100 mg of nomifensine). We found an extraordinary heterogeneity of antibody response. Only five antibodies appeared to be primarily reactive with nomifensine. The remaining antibodies reacted either optimally or exclusively in the presence of one or more of the metabolites. Three of the metabolite-specific antibodies were positive only in the presence of ex vivo antigens, indicating specificity for as-yet-unidentified early and late metabolites of nomifensine. All the antibodies were capable of activating complement and belonged to the IgG or IgM class or both. Two serum samples also contained weak IgA antibodies. In addition to a variable degree of cross reactivity of the antibodies, at least one serum sample had two drug-dependent red-cell antibodies (IgG against nomifensine and IgM against metabolites), and one sample had a drug-dependent IgM red-cell antibody and an IgG platelet antibody. Despite their serologic heterogeneity, all the antibodies were strongly reactive with ex vivo antigens. We recommend the use of ex vivo antigens as the technique of choice for the detection of nomifensine-dependent (and probably other drug-dependent) antibodies. PMID- 4022081 TI - Value of the QRS duration versus the serum drug level in predicting seizures and ventricular arrhythmias after an acute overdose of tricyclic antidepressants. AB - There is a need for a rapid predictor of potential clinical severity to guide therapy in patients with an acute overdose of tricyclic antidepressant drugs. We performed a prospective study of 49 such patients to observe the associations among serum drug levels, maximal limb-lead QRS duration, and the incidence of seizures and ventricular arrhythmias. Patients were divided into two groups on the basis of maximal limb-lead QRS duration. Group A (13 patients) had a duration of less than 0.10 second, and Group B (36 patients) had a QRS duration of 0.10 second or longer. No seizures or ventricular arrhythmias occurred in Group A. In Group B there was a 34 per cent incidence of seizures and a 14 per cent incidence of ventricular arrhythmias. All patients survived. Serum drug levels failed to predict the risk of seizures or ventricular arrhythmias accurately. Seizures occurred at any QRS duration of 0.10 second or longer (P less than 0.05), but ventricular arrhythmias were seen only with a QRS duration of 0.16 second or longer (P less than 0.0005). We conclude that determination of the maximal limb lead QRS duration predicts the risk of seizures and ventricular arrhythmias in acute overdose with tricyclic antidepressants. Serum drug levels are not of predictive value. PMID- 4022082 TI - Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 34-1985. A 32-year-old man with granulomatous myocarditis and cardiac failure. PMID- 4022084 TI - Clinical use of antidepressant blood levels and the electrocardiogram. PMID- 4022083 TI - Drug-induced immune hemolysis. PMID- 4022085 TI - Matching prescription drugs and consumers. The benefits of direct advertising. PMID- 4022086 TI - Management of asthma during pregnancy. PMID- 4022087 TI - A possible teratogenic effect of propranolol. PMID- 4022089 TI - Physicians' fees. PMID- 4022088 TI - Identification of human osteoclasts with monoclonal antibodies. PMID- 4022090 TI - Clonal rearrangements of T-cell receptor genes in mycosis fungoides and dermatopathic lymphadenopathy. AB - Histologic diagnosis of mycosis fungoides may be difficult, especially in lymph nodes that show changes frequently associated with chronic skin disease. As an alternative approach to diagnosis, we have analyzed the configuration of DNA for the beta T-cell receptor genes in biopsy tissues from 14 patients with mycosis fungoides. Clonal rearrangements of these genes were found in each specimen tht contained histologically unambiguous mycosis fungoides. Clonal rearrangements were also found in seven of nine lymph nodes removed from patients with mycosis fungoides and considered histologically to contain only benign lymphadenopathy. Matching rearrangements of beta T-cell receptor genes were detected in benign lymph nodes and histologically involved tissues when paired specimens were available from the same cases. Our findings provide molecular evidence for the clonal T-cell origin of mycosis fungoides and indicate the high incidence of extracutaneous disease in patients with palpable lymphadenopathy. In addition, this study demonstrates that the detection of rearranged T-cell receptor genes can be a sensitive and practical method for the diagnosis and characterization of T-cell neoplasms. PMID- 4022091 TI - Response to measles vaccine in Haitian infants 6 to 12 months old. Influence of maternal antibodies, malnutrition, and concurrent illnesses. AB - To study the factors affecting the serologic response to measles vaccination, we evaluated 595 Haitian infants from 6 through 12 months of age, and their mothers, at the beginning of an immunization program. Thirty-four per cent of the infants had preexisting serologic evidence of measles infections by 11 months of age. Among infants more than nine months of age, those who had had measles had a significantly lower nutritional status than those who had not (P less than 0.01). After vaccination, seroconversion rates increased from 45 per cent at 6 months to 100 per cent at 12 months. The lowest rate of vaccine failure compatible with acceptably low rates of natural infections could be achieved by vaccination after eight months of age. Infants born to mothers with low levels of antibody to measles (hemagglutination-inhibition antibody titers less than 1:40) were significantly more likely to have had natural measles (P less than 0.01) or to have seroconversion after vaccination (P less than 0.001) at 6 to 10 months of age than were infants born to mothers with higher of age than were infants born to mothers with higher titers. Malnutrition and acute infections did not affect seroconversion rates. These data support the World Health Organization recommendation to administer measles vaccine in under-developed countries as soon after nine months of age as possible, regardless of nutritional status or the presence of minor illnesses. PMID- 4022093 TI - Possible association of measles virus infection with rheumatic fever. PMID- 4022092 TI - Measles--forgotten but not gone. PMID- 4022094 TI - Renal retention of potassium in fruit. PMID- 4022095 TI - Case 15-1985. PMID- 4022096 TI - Treatment of rheumatoid arthritis in HMOs or in fee-for-service practice. PMID- 4022097 TI - Megacorporate health care. PMID- 4022098 TI - The relation of faculty academic activity to financing sources in a department of medicine. PMID- 4022099 TI - Presidential illness and prevention of disease. PMID- 4022100 TI - Bearing the news. PMID- 4022101 TI - [Hematologic changes in rats following exposure to dichlorvos]. AB - Two different experiments on rats were carried out: an acute intoxication causing clinical symptoms and a subchronical intoxication without any symptoms. After the acute experiment an increase of hemoglobin- and hematocrite values as well as of the mean corpuscular hemoglobin concentration was found. These differences are interpreted to be an increased erythropoiesis after hypoxia. Following the subchronical experiment the parameters mentioned above had decreased. These results linked up to anisocytosis, poikilocytosis and/or polychromasia in 30% of the treated animals and allow to assume a disorder of erythropoiesis. The results require to take in consideration a prophylactic hematological survey of long-term exposed people. PMID- 4022102 TI - [The herbicide propachlor--14 C synthesis, toxicologic problems and methodology studies on the determination of residues in corn, potatoes, water and soil]. AB - Using the synthesized agent propachlor (N-isopropyl-2-chloroacetanilid) labelled with 14C, methodical investigations revealed an extremely high steam volatility not being assumed before because of the low vapour pressure. The method of steam distillation basing on this fact is of universal application to the processing of maize, potatoes, water, and soil, in which propachlor could be quantitatively determined by gas chromatography with a detection sensitivity of 0.02 ppm. Furthermore, this methods allows a simple purification of the raw product of synthesis containing impurities up to 20%. Propachlor codistilled with steam had a purity of more than 99%. Possibly, the high steam volatility of propachlor could have economic and toxicological consequences as to its application (volatilization in the open air with a high atmospheric humidity along with high temperatures). Therefore, an investigation of the steam volatility in the general screening programme for new agents is to be recommended in addition to the usual investigations of steam pressure. PMID- 4022103 TI - Bacteria and food poisoning organisms in milk. AB - Individual milk samples of 50 goats, 50 ewes and 50 cows were examined for the total viable count, coliform bacteria, staphylococci and salmonellae. Growth of enterotoxin A producing Staphylococcus aureus NCTC 10652 in the milk of the three animal species was also studied. The average total count was 1.9 X 10(7) cells/ml for cow's, 7.7 X 10(6) for goat's and 2.7 X 10(6) for ewe's milk with micrococci staphylococci, rods and streptococci being the predominant organisms in the three milks, respectively. Goat's milk contained the lowest numbers of coliforms and ewe's milk the highest numbers. Staphylococcus aureus could not be detected in goat's milk, whilst 16 and 26% of the ewe's and cow's milk samples contained 100 and 80 cells/ml, respectively. Out of 39 coagulase positive staphylococci, 27 were thermonuclease positive, 18 produced lecithinase and 15 fermented mannitol. Red blood cells of sheep origin were much more resistant to lysis by ewe's strains compared to bovine strains. Growth curves of Staphylococcus aureus were nearly linear at 17 degrees C but exponential at 31 degrees C without lag phase. Hazardous numbers of about 10(6) cells/ml were readily reached at 31 degrees C after 6 h and at 17 degrees C after 18 h. Salmonellae could not be detected in any of the samples examined. Out of 19 enterobacteria suspected to be salmonellae 11 proved to be Proteus and 8 Citrobacter. PMID- 4022104 TI - Determination of the decomposition products of Usal in model systems and determination of dioxopiperazine in soft drinks by HPLC. AB - A HPLC method for the determination of Usal (Aspartame hydrochloride, L-aspartyl L-phenylalanine methyl ester hydrochloride) and its decomposition products was elaborated. Aspartic acid, phenylalanine, phenylalanine methyl ester, aspartyl phenylalanine, phenylalanyl-aspartic acid, 5-benzyl-3,6-dioxo-2-piperazineacetic acid (DOP) and Usal were separated on Separon SI C-18. The mobile phase was: 0.5 M NaH2PO4 (pH 2.1) and methanol (85:15 v/v). The detection was carried out at 200 nm. The method for DOP determination was tested by the analysis of 10 types of soft drinks to which DOP was added. In two newly developed sorts of soft drinks sweetened with Usal the formation of DOP was followed during storage. The DOP increment after 34 days of storage reached 0.7 and 6 mg/l at 7 and 20 degrees C, resp. The method is also suitable for DOP determination in the sweetener itself. PMID- 4022105 TI - [Identification and determination of phosphates in dairy products]. AB - This paper outlines the thin-layer chromatographic separation of condensed phosphates on polyamide-starch layers with subsequent digestion of the spots and photometric identification of the phosphates. With cheese and condensed milk the preparation of samples is carried out by isolation of the phosphate solution after protein precipitation by trichloroacetic acid. With pure phosphate solutions a recovery rate of 95.9% +/- 3.1% was established, whereas the recovery rate of added phosphate from processed cheese and condensed milk was 82.7% +/- 5.9%. PMID- 4022106 TI - [Distribution of free carboxyl groups in native pectins from fruits and vegetables]. AB - Pectins from 18 kinds of fruit and vegetable are extracted with ammonium oxalate from the alcohol-insoluble substance and fractioned on DEAE-Sephacell. All the fruit pectins as well as tomato and sunflower pectin have in their distribution of the esterification degree a concentration maximum in the highly esterified range, that is above an esterification degree of 60%. With lower esterification degrees the concentration decreased continuously. Vegetable pectins from cucumbers, celery, and tomato-paprika (sweet, red) have their maximum within an esterification range of 50-60%. The carboxyl groups are randomly distributed in all these preparations. As against that, vegetable pectins from red and white cabbage, cauliflower, large radish and carrots have in addition to a pectin fraction with randomly distributed carboxyl groups another one, pectin molecules of which have blocks of free carboxyl groups. The latter fraction may constitute up to 50% of the pectin. PMID- 4022107 TI - [The enzymatic degradation of DDT. 3. Metabolism of DDT]. AB - DDT orally given to rats is converted into DDD by reductive dechlorination in the liver within 30 min. 6 h after a single application of 10 mg DDT per rat a quantity of 60 mg DDD/kg was indicated in the liver. DDT is stored in the adrenal glands; in the other organs an equilibrium comes up obviously, even with further application. The quantitative ratios are reported. Information on the experimental details of DDT determination and--anticipatory to the following publications--on the analysis of the most relevant metabolites is given. PMID- 4022108 TI - [The enzymatic degradation of DDT. 4. Degradation of DDD (dichlorodiphenyldichloroethane)]. AB - DDD is formed from DDT by reductive dechlorination. After application of DDD to rats the dechlorination product DDMU could be detected only after short exposures in the organs, in high concentrations, however, permanently in the faeces. The distribution of DDD in the organism of the rats is studied. PMID- 4022109 TI - [Toxicologic study of maneb in rats from small or large nests]. PMID- 4022110 TI - [Ultrastructure of fat cells of obese patients with diabetes mellitus before and after treatment with a reducing diet]. AB - Ultrastructural investigation of lipocytes of obese diabetics (Diabetes mellitus) before and after treatment with a reducing diet 21 diabetics not depending on insulin with obesity of the second or third degree were given for 3 months a reducing diet containing 5110 kJ/day (86 g protein, 41 g fat, 119 g carbohydrates). After treatment the test persons had a loss of weight of 7.60 kg on average. Before and after treatment subcutaneous adipose tissue was taken by puncture biopsy and investigated by electron microscopy. After treatment extended intercellular spaces are evident in which collagenic and elastic fibres appear quantitatively enlarged. A certain plication and inequality of the cell membranes, a penetration of the fat droplet by cytoplasmatic outgrowths as well as a diminution of the lipocytes and the big fat droplet were found. The investigations show that even the relatively short treatment of 3 months exercises an influence on the structure of the lipocytes. That shows new possibilities of therapy and prophylaxis of obesity. PMID- 4022111 TI - Reactions of oxidized lipids with protein. Part 13. Autoxidation of hexanal in presence of nonlipidic components. AB - Hexanal is rapidly autoxidized in mixture with nonlipidic substrates even at 25 degrees C. The formation of peroxides follows the kinetics of a first order reaction with respect to hexanal (k1 about 10(-5) min-1), and is higher in mixture with casein or lysine-impregnated cellulose than with cellulose. In mixtures containing pure hexanal, peroxides are decomposed more rapidly after second-order reaction with respect to peroxides (k2 about 10(-3) mmol X kg-1 X min-1) while only slowly by the first-order reaction (k3 about 10(-5) min-1). In presence of small amounts of hexanoic acid the rate of second-order peroxide decomposition remained unaffected while the rate of the first-order peroxide decomposition increased by 4 orders (k3 about 10(-1) min-1). The presence of peroxides was percepted in the odour by sensory analysis contrary to nonvolatile lipid hydroperoxides. PMID- 4022112 TI - Determination of nitrates in milk by ion-chromatography. AB - A method is described for the determination of nitrates in cow milk, human milk, milk powder or milk-based infant formulae using liquid chromatography on Spheron DEAE and a direct photometric detection (205 nm). The influence of removing proteins by precipitation with Carrez reagent on the accuracy of determination was studied. The proposed method gives identical results with the reference method (photometry after reduction of nitrate to nitrite) but is more rapid. Its limit of determination is 0.5 mg NO3-/l of milk, its reproducibility is 4% (relative standard deviation). PMID- 4022113 TI - [The metabolism of fenazox in tomato plants]. AB - Results from investigations on the metabolism of 14C-Fenazox show that in 6-8 weeks old tomato-plants (sort "Harzfeuer") the agent undergoes a biotransformation. After chromatographic separation the structure of the biotransformation products was elucidated by comparison to authentic test substances, by derivatization as well as by means of physico-chemical methods. With that, the following metabolites were identified: non-transformed Fenazox, o hydroxyazobenzene, o-hydroxyaniline, and p-hydroxyaniline. Probably, the agent is first transformed enzymatically or non-enzymatically into o-hydroxyazobenzene, then follows a reductive cleavage into o-hydroxyaniline and aniline. In its turn, the latter is transformed into o-hydroxy- and p-hydroxyaniline. Experiments in the field of transformation kinetics indicated that the concentration of the applied Fenazox rapidly decreases and that the first transformation product o hydroxyazobenzene in the beginning increases and then again decreases in its concentration. With increasing application time it comes to an increase of the non-extractable residues. PMID- 4022114 TI - Some biochemical properties of trypsin inhibitor type antinutrients derived from extracts of wheat grain, Beta variety. AB - Trypsin inhibitors were isolated and partially purified from wheat grain, Beta variety. The procedure for determination of the inhibitory activity was simplified. This pertains shortening of the reaction time as well as quantitative decrease of components in the incubation mixture. The inhibitory fraction was salted out at 30-65% ammonium sulfate saturation. The experimental material has not been initially defatted. For isolation of the inhibitors pH 4.4 was demonstrated to be optimal. The trypsin inhibitor was characterized by relatively low activity against trypsin (1.5% of soya inhibitory activity). Preparations showing inhibitory properties when stored at -18 degrees C retained their original activity for 40 days, whereas at 4 degrees C only for 10 days, respectively. Storage at 18 degrees C for 10 days resulted in 50% loss of the original activity. Among various factors stabilizing the inhibitory activity being studied, 2-mercaptoethanol at 0.01% final concentration was found to be most effective. Study on the effect of temperature on the antitrypsin activity revealed that the preparation retained its initial activity up to 80 degrees C. It has been demonstrated by wheat proteins fractionation that both albumin and globulin fractions were accompanied by the antitrypsin activity. Moreover gluten was also shown to exhibit some inhibitory activity. Variations in the inhibitory activity were evidenced during germination of wheat grain. After 2 days period of germination it tended to decrease, disappearing completely at the fifth day, respectively. The inhibitory activity appeared in coleoptile and root at fourth day of germination, being higher in coleoptile than in the roots. PMID- 4022115 TI - [The enzymatic degradation of DDT. 5. Direct transformation of DDD (dichlorodiphenyldichloroethane) into an aldehyde]. AB - The chemical-preparative preparation of the aldehyde (DDHO) is possible by using of saponification. Its enzymatic formation in the organism of warm-blooded animals has not been described up to now. The identification of the aldehyde after application of DDD to rats was successful, inspite of the inhibition of the HCl-cleaving consecutive reactions, whereby the enzymatic formation of the aldehyde was indicated. A possible reaction mechanism is presented. PMID- 4022116 TI - Studies on fish protein concentrate and fish meal from river Nile bolti fish (Tilapia nilotica). AB - Fish protein concentrate (FPC) from river Nile bolti fish (Tilapia nilotica) was prepared and compared with commercial FPC and fresh bolti fish flesh. Fish meal (FM) from bolti fish offals was prepared and compared with commercial FM and also fresh bolti fish flesh. FPC from bolti fish showed a higher crude protein content but less fat, ash, calcium and sand than the commercial sample, while FM from bolti fish showed a higher content of ash and phosphorus than commercial FM but was nearly similar in crude protein, fat, calcium and sodium chloride. FPC from bolti fish had a higher content of lysine, arginine, aspartic acid, glycine and glutamic acid and a lower content of the other free amino acids. The bolti fish FM had a lower content of total amino acids and the contents of the free amino acids cysteine, glycine, aspartic acid, serine, alanine, valine, and methionine increased slightly. The yield was 12% for FPC and 19.5% for FM. Coliform bacteria were not present in both FPC and FM from bolti fish. Low moisture contents of FPC and FM were essential for preventing microbiol growth and to attain a good keeping quality. The FPC and FM from bolti fish reached moisture equilibrium and stopped increasing in weight within 144 to 192 h. PMID- 4022117 TI - [The neurotoxicity and mutagenicity of phenylmercury acetate and nitrate in single and combined applications in animal studies]. PMID- 4022118 TI - Excretion of thiocyanate in urine of growing pigs after rapeseed meal feeding. PMID- 4022119 TI - A clam with a difference. PMID- 4022120 TI - Components of a cocktail. PMID- 4022121 TI - Welcome whiff of biochemistry. PMID- 4022122 TI - Vaccination with purified microgamete antigens prevents transmission of rodent malaria. AB - Malaria vaccination with preparations of microgametes has been shown to inhibit transmission of Plasmodium spp. to the mosquito vectors of avian, rodent and simian parasites. This transmission-blocking immunity results from the induction of microgamete-agglutinating antibodies in the vaccinated host which, when ingested in a mosquito blood meal, react with exflagellating microgametes in the midgut to prevent fertilization and oocyst development. Here we have passively transferred the immunity with gamete-specific monoclonal antibodies raised against the rodent malaria parasite Plasmodium yoelii nigeriensis, and an IgG2a isotype monoclonal antibody from a hybridoma cell line, PYG-1, has been used to identify the target antigens on the gametes and to affinity-purify sufficient quantities of specific gamete antigen to facilitate vaccination studies. This transmission-blocking monoclonal antibody immunoprecipitated microgamete antigens of apparent relative molecular mass (Mr), 67K (67,000), 59K, 57K, 42K and 35K. Immunization of mice with these proteins before infection and mosquito feeding led to a 85-99.7% reduction in transmission to the mosquito vector; vaccination via intravenous or intramuscular routes was equally effective and did not require an adjuvant. PMID- 4022123 TI - Cooperative dimeric and tetrameric clam haemoglobins are novel assemblages of myoglobin folds. AB - Cooperative functioning of many protein systems depends on communication between different subunits of those systems. Perhaps the best understood cooperative protein system is the vertebrate haemoglobin tetramer, in which the subunits share a similar tertiary structure (the myoglobin fold) with each other and with myoglobins and haemoglobins from at least four different animal phyla and leguminous plants. Blood clams have cooperative tetrameric haemoglobin. In view of previous reports concerning the role of dimers in the vertebrate tetramer, the clam haemoglobins represent a very interesting model system. We report here the low-resolution three-dimensional crystal structures of the dimeric and tetrameric cooperative haemoglobins from the blood clam Scapharca inaequivalvis. We find that clam haemoglobins are made of myoglobin-like subunits but their assembly to form dimers and tetramers is quite different from that of vertebrate haemoglobin. The arrangement of the subunits provides a simple structural explanation for haem haem interaction in the dimer and tetramer. PMID- 4022124 TI - Weak and strong crossbridges. PMID- 4022125 TI - Mapping of general anaesthetic target sites provides a molecular basis for cutoff effects. AB - A longstanding and unresolved problem in general anaesthesia is the so-called 'cutoff' effect; as one ascends a homologous series of anaesthetic agents, the potencies progressively increase with anaesthetic size but then, rather suddenly, anaesthetic potency disappears. Curiously, this cutoff in potency occurs at very different points in different series. Various explanations have been offered, usually based on the notion that lipid bilayers are the primary target sites in general anaesthesia. However, accumulating evidence now suggests that proteins are the primary sites of action. Here we demonstrate cutoff effects for the anaesthetic inhibition of a soluble protein (firefly luciferase) which mirror those found for general anaesthesia, and we describe how the molecular architecture of the binding site accounts for the different cutoffs in the different homologous series. We show that this behaviour is a natural consequence of anaesthetics binding to an amphiphilic protein pocket of circumscribed dimensions. When general anaesthetic target sites in animals and the luciferase protein are mapped out using the fine details of the potency data, remarkable similarities are revealed. Our results thus suggest that the target sites in general anaesthesia are amphiphilic pockets on proteins. PMID- 4022126 TI - Subtle structural alterations in the chains of type I procollagen produce osteogenesis imperfecta type II. AB - Although the perinatal lethal form of osteogenesis imperfecta (OI type II) occasionally results from large rearrangements within the genes encoding type I collagen, most mutations are far more subtle. The complexity of the human collagen genes precludes cloning and sequencing each gene from every patient, and we have therefore developed an approach to localizing mutations at the protein level. We report here that cells cultured from 15 infants with OI type II synthesized both normal type I procollagen and a form that was unstable, poorly secreted and excessively modified. Abnormal procollagen from different strains was overmodified to different extents. The patterns of overmodification we observed are best explained by mutations that disrupt the Gly-X-Y sequence of pro alpha chains, and thus alter the rate of propagation of triple helix from COOH terminus to NH2-terminus. As a consequence, a given mutation allows overmodification of all three chains in a molecule NH2-terminal to its position in the triple helix. PMID- 4022127 TI - Sliding distance of actin filament induced by a myosin crossbridge during one ATP hydrolysis cycle. AB - Muscle contraction results from a sliding movement of actin filaments induced by myosin crossbridges on hydrolysis of ATP, and many non-muscle cells are thought to move using a similar mechanism. The molecular mechanism of muscle contraction, however, is not completely understood. One of the major problems is the mechanochemical coupling at high velocity under near-zero load. Here, we report measurements of the sliding distance of an actin filament induced by a myosin crossbridge during one ATP hydrolysis cycle in an unloaded condition. We used single sarcomeres from which the Z-lines, structures which anchor the thin filaments in the sarcomere, had been completely removed by calcium-activated neutral protease (CANP) and trypsin, and measured both the sliding velocity of single actin filaments along myosin filaments and the ATPase activity during sliding. Our results show that the average sliding distance of the actin filament is less than or equal to 600 A during one ATP cycle, much longer than the length of power stroke of myosin crossbridges deduced from mechanical studies of muscle, which is of the order of 80 A (for example, ref. 15). PMID- 4022128 TI - Research responsibility. PMID- 4022129 TI - Ageing society. PMID- 4022130 TI - Ragweed in China. PMID- 4022131 TI - The many merits of monoclonals. PMID- 4022132 TI - Cognitive neuropsychology: a fruit by any other name. PMID- 4022133 TI - Children judge by the length. PMID- 4022134 TI - Category-specific naming deficit following cerebral infarction. AB - Studies aimed at characterizing the operation of cognitive functions in normal individuals have examined data from patients with focal cerebral insult. These studies assume that brain damage impairs functions of the cognitive processes along lines that honour the 'normal' pre-morbid organization of the cognitive system. For example, detailed study of individual brain-damaged patients has revealed apparently selective disruption of cognitive functions such as auditory/verbal working memory, phonological processing ability, grapheme-to phoneme translation procedures and semantic processing. Warrington et al. have studied patients with even more fine-grained selective disturbances of the semantic system. The most selective deficits have been reported for four patients who were significantly better at identifying inanimate objects than they were at identifying living things and foods. These patterns of selective deficit after localized brain damage provide important information about the normal organization of the lexicon, and ultimately about how components of the lexical system are related to particular neural substrates. Here, we report a case study of a patient demonstrating a very selective disturbance of the ability to name items from two related semantic categories. Despite normal performance on a large battery of lexical/semantic tasks, the patient shows a consistent and striking disability in naming members of the semantic categories of 'fruits' and 'vegetables'. The selectivity of this deficit supports a category-specific organization of the mental lexicon, and suggests independence of the processing routes involving naming and name recognition. PMID- 4022135 TI - 3H-(-)DO 710 discriminates guanine nucleotide sensitive and insensitive dopamine binding sites. AB - (-)DO 710, a substituted benzamide derivative which discriminates dopamine D-2 and D-4 binding sites (Sokoloff et al. 1984), and antagonises in a differential manner several apomorphine-induced behavioral responses (Schwartz et al. 1984) was tritiated and used namely to differentially label the D-4 site. In striatum the 3H-(-)DO 710 saturation curve was best explained by the presence of two classes of sites with a 7-fold difference in affinity (Kd values of 3.0 nM and 0.42 nM) and Bmax values of 316 and 106 fmol X mg protein-1, respectively which correspond to the D-2 and D-4 sites (Sokoloff et al. 1984). In spite of its limited selectivity, 3H-(-)DO 710 in low concentration (0.2 nM) could be used to preferentially label striatal D-4 site as shown by the inhibition potencies of discriminant benzamide derivatives (DBD), significantly higher than at pituitary D-2 site (receptor) whereas classical neuroleptics including metoclopramide were equally potent at both sites. The affinity of a variety of agonists for striatal sites labeled with 0.2 nM 3H-(-)DO 710 generally differed from their affinity for the two states of the pituitary D-2 receptor (with high and low affinity for agonists, respectively); compounds like lisuride, N-propylnorapomorphine or pergolide had very high affinity for the striatal 3H-(-)DO 710 site. In pituitary from oestradiol-treated rats, where only D-2 site occurs, only the low-affinity site for 3H-(-)DO 710 (Kd = 2.8 nM) was found.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4022136 TI - Very rapid turnover of dopamine in noradrenaline cell body regions. AB - The contents of dopamine, noradrenaline and their deaminated metabolites, 3,4 dihydroxyphenylacetic acid (DOPAC) and 3,4-dihydroxyphenylethylene glycol (DOPEG) were determined in rats in two noradrenaline cell body regions, i.e., the superior cervical ganglion and the locus coeruleus, and in one dopamine cell body region, the substantia nigra. In the two noradrenaline cell body regions, the tyrosine hydroxylase inhibitor alpha-methyltyrosine rapidly lowered the contents of noradrenaline and DOPEG and it lowered the contents of dopamine and DOPAC even more rapidly. The dopamine-beta-hydroxylase inhibitor FLA-63 swiftly elevated the content of dopamine and it lowered the content of noradrenaline in the two noradrenaline regions, but it was ineffective in the substantia nigra. The monoamine oxidase inhibitor pargyline rapidly reduced the deaminated catechols and increased somewhat the contents of the two amines in the superior cervical ganglion and in the locus coeruleus. The alpha-methyltyrosine-induced disappearance of dopamine in the two noradrenaline cell body regions was markedly inhibited by FLA-63 and pargyline in combination, but not by only one of the two drugs. The results indicate that most of the dopamine in the superior cervical ganglion and in the locus coeruleus occurs in the cell body region of noradrenaline neurons, whereas only a minor part of the dopamine in the superior cervical ganglion is present in SIF cells. Axonal transport did not contribute to the disappearance of dopamine in the superior cervical ganglion. A high dose of reserpine reduced the contents of dopamine and noradrenaline in the superior cervical ganglion and in the locus coeruleus, indicating that most of the amines is present in storage granules.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4022137 TI - The handling of five catecholamines by the extraneuronal O-methylating system of the rat heart. AB - In a comparative study, the handling of five catecholamines by the extraneuronal O-methylating system of the rat heart was determined; all rats were pretreated with reserpine, monoamine oxidase and neuronal uptake were inhibited in all experiments. Hearts were perfused for 7 min with a tracer concentration of 3H-(+/ )-isoprenaline, either in the absence or in the presence of unlabelled catecholamines (which reduced the O-methylation of the tracer amine). IC50's were determined for unlabelled catecholamines and then converted to "half-saturating outside concentrations", i.e., to those concentrations in the perfusion fluid that half-saturate the intracellular catechol-O-methyl transferase (COMT). The values for the (-)-isomers of dobutamine, isoprenaline, adrenaline and noradrenaline and that for dopamine were low and rather similar (between 0.67 and 2.7 mumol/l). Stereoselectivity for isoprenaline probably reflected the preference of uptake2 for the (-)-isomer. The effects of (-)- and (+)-dobutamine indicated that both isomers are a) transported by uptake2 and b) good substrates of COMT. The Vmax for O-methylation [determined for 3H-(+/-)-isoprenaline, 3H-(+/ )-adrenaline, 3H-(+/-)-noradrenaline and 3H-dopamine] was rather similar for all four catecholamines. It is concluded that the extraneuronal O-methylating system of the rat heart handles the five catecholamines in a similar manner, although the Km for uptake2 had been found to increase substantially in the order: dobutamine less than isoprenaline less than adrenaline less than noradrenaline less than dopamine (Grohmann and Trendelenburg 1984b). PMID- 4022139 TI - [Sperm donorship and anonymity]. PMID- 4022138 TI - On the reversibility of reversible MAO inhibitors. AB - The aim of this study was to assess a) the validity of an ex vivo approach for the estimation of the in vivo MAO A inhibitory properties of the new short-acting MAO A inhibitors, amiflamine, brofaremine, cimoxatone and moclobemide, by studying the effect of dilution of brain and liver homogenates from pretreated rats on the degree of enzyme inhibition; b) the displaceability of the inhibitors from the enzyme by substrate in brain and liver homogenates from pretreated rats; c) idem, in the in vivo situation in the brain, by increasing the availability of the substrate by releasing it from its endogenous stores by tetrabenazine. The following results were obtained: The ex vivo approach was found to be valid for moclobemide in brain and liver and for cimoxatone in brain tissue; a slight underestimation of the MAO A inhibitory effect of the latter in the liver is likely. Definite underestimation occurred with amiflamine in both tissues. Kinetic investigations using homogenates from pretreated rats showed amiflamine to be a competitive inhibitor; cimoxatone was competitive in the liver but showed a more complex pattern in the brain. Moclobemide was noncompetitive in both tissues, as has been shown previously for brofaremine. Moclobemide prevented the deamination of dopamine and serotonin released from their striatal stores by tetrabenazine nearly as efficiently as clorgyline at an otherwise equieffective dose; cimoxatone was somewhat less effective relative to the reference compound, as was brofaremine, which was however given at a more effective dose. Amiflamine was much less effective than clorgyline at protecting dopamine, but equieffective with respect to serotonin.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4022140 TI - [The causes of venous thrombosis and lung embolism]. PMID- 4022141 TI - [Significance of the differential leukocyte count for the demonstration and the exclusion of the presence of atypical cells]. PMID- 4022142 TI - [The seton method for the treatment of perianal fistula located outside of the sphincter]. PMID- 4022143 TI - [Treatment of orbital rhabdomyosarcoma]. PMID- 4022144 TI - [Stress incontinence in women; results of the Stamey-Pereyra surgical treatment method]. PMID- 4022146 TI - [Report from the Public Health Council on vaccination against hepatitis B]. PMID- 4022145 TI - [Transient hypothyroidism due to skin contamination with iodine in a newborn infant with an omphalocele]. PMID- 4022147 TI - [Transplantation of organs; various juridical observations]. PMID- 4022148 TI - [The undoing of a urinary diversion formerly considered definitive]. PMID- 4022149 TI - [Reduced protein diet and the progression of kidney insufficiency]. PMID- 4022150 TI - [Smoking and disease]. PMID- 4022151 TI - [Treatment under coercion]. PMID- 4022152 TI - [Demand and supply in the laboratory diagnosis of thyroid gland function]. PMID- 4022153 TI - [A patient with eumycetoma in the Netherlands]. PMID- 4022154 TI - [Policy, ethics and values in health care]. PMID- 4022155 TI - [Importance of recombinant DNA studies for the identification of carriers of Duchenne's muscular dystrophy]. PMID- 4022156 TI - [Treatment of progressive idiopathic scoliosis using braces; a follow-up study]. PMID- 4022157 TI - [Chronic bromide poisoning]. PMID- 4022158 TI - [Acoustic neuroma: from neurological to otological diagnosis]. PMID- 4022159 TI - [Recommendation of the Public Health Council concerning contact lens specialists and the law on occupations within the personal health care field]. PMID- 4022160 TI - [Mortality rate of operations for gallstone disease]. PMID- 4022161 TI - [Converging trends in schizophrenia research]. PMID- 4022162 TI - [The clinical fatality of operations for gallstone disease]. PMID- 4022163 TI - [Pericardiocentesis: a safe drainage method for subacute heart tamponade]. PMID- 4022164 TI - [Cholesteatoma in the medial part of the petrous bone and the modified transotic approach]. PMID- 4022165 TI - [Abdominal pain and nocturnal sweating, a special combination]. PMID- 4022166 TI - [Damage from light and sunglasses]. PMID- 4022167 TI - [Medical aspects of diving accidents]. PMID- 4022168 TI - [How often need a booster dose be given after desensitization with bee and wasp venom?]. PMID- 4022169 TI - [Medical emergency service by the ANWB (General Dutch Automobile Club) Emergency Center]. PMID- 4022170 TI - [Risks and considerations in air travel for patients with lung or heart disorders]. PMID- 4022171 TI - [Non-typhoid Salmonella bacteremia; a retrospective study in 33 adults ]. PMID- 4022172 TI - [Intracutaneous hepatitis B vaccination]. PMID- 4022173 TI - [Boutonneuse fever contracted at a camp site in southern France]. PMID- 4022174 TI - [Can one predict whether a future insect bite will provoke a generalized reaction?]. PMID- 4022175 TI - [The policy in syphilis]. PMID- 4022176 TI - [Hepatitis B vaccination; administration in the arm or buttock?]. PMID- 4022178 TI - [Characteristics of monosynaptic connections between neurons of the callosal system and specific thalamic nuclei]. AB - In the sensorimotor cortex of awake rabbits monosynaptic afferent and efferent connections of callosal neurons (CN) with ipsilateral specific thalamic nuclei (ventral posterolateral, ventral posteromedial, ventral lateral and anteroventral nuclei) were analyzed by electrophysiological method and compared with those of target-units of callosal fibres (TU). It was demonstrated that CN and TU differed in their monosynaptic inputs from the thalamus and in their axons projecting to these structures and/or being a part of the pyramidal tract. These differences were the following: a greater portion of TU had the descending projections (54%) as compared with CN (14%); 22% of TU responded by monosynaptic action potentials to the stimulation of specific thalamic nuclei, while CN never manifested such responses. TU could project to the thalamus through the main axon stem as well as through the collaterals of the pyramidal tract axons. It is supposed that the discovered differences evidence for the much greater convergence of the thalamic relay neuron effect on TU, thus revealing the mechanism underlying the differences both in receptive field properties and in the background and evoked activity of CN and neurons synaptically excited in response to the transcallosal stimulation. PMID- 4022177 TI - [Organization of the substructure of the receptive fields of neurons of the lateral suprasylvian area of the cat cortex]. AB - The substructure of receptive fields of the lateral suprasylvian area neurons was investigated in cats. It was shown that the majority of receptive fields investigated were organized of subelements with different qualitative characteristics according to their responses to moving visual stimuli. With the unmasking method of stimulation, small amplitudes of the motion evoked, as a rule, directional responses, whereas with the masking method the same amplitude of the motion produced nondirectional responses. Some receptive fields of the investigated neurons responded vigorously to the motion of borders of the visual stimuli. The heterogeneity in organization of the substructure of the receptive fields was explained by the convergence of different inputs to the investigated neurons. PMID- 4022179 TI - [Effect of vasopressin and oxytocin on the spontaneous activity of dorsal horn cells of the isolated spinal cord of the rat pup]. AB - The effect of vasopressin and oxytocin on background frequency of single cells from the dorsal horn was studied in the isolated spinal cord of 2-3 weeks old rats. It was shown that neurons were predominantly depressed following application both of vasopressin or oxytocin. Vasopressin evoked depression of background activity in 74% cells (29 of 39 responding to vasopressin) and activation in 26% cells (10 from 39). Oxytocin evoked depression in 67% (14 from 21 responding to oxytocin) and activation in 33% cells (7 from 21). All effects were reversible and dose-dependent. Neurons studied either gave the same response both to vasopressin and to oxytoxin or responded only to one of the two peptides. PMID- 4022180 TI - [Activity of propriospinal neurons of segments C3 and C4 during "fictive locomotion" in the cat]. AB - The activity of C3-C4 propriospinal neurons was recorded during "fictitious locomotion" of forelimbs in immobilized decerebrated cats with the spinal cord transected at the lower thoracal level. The neurons were identified by the antidromic responses to stimulation of the lateral funiculus in the C6 segment. Most of the neurons (70%) were antidromically activated also from the lateral reticular nucleus. The discharge frequency of most neurons was rhythmically modulated in correlation with the motoneuron activity during "fictitious locomotion", i.e. in the absence of any rhythmical signals from the limb receptors. The cooling of the rostral area of the cervical enlargement abolished both the generation of the locomotor rhythm and the rhythmical activity of the propriospinal neurons. Therefore intraspinal mechanisms controlling the forelimb activity are the main source for rhythmical modulation of the C3-C4 propriospinal neurons. PMID- 4022181 TI - [Effect of electric stimulation of the septum of the rabbit brain on subiculum cells with different types of spontaneous activity]. AB - Neuronal activity was recorded extracellularly in subiculum of unanaesthetized rabbits during stimulation of the medial septal nucleus and hippocampal field CA1. According to the pattern of the background activity subicular cells were divided into three groups: cells with theta-modulation, cells with delta modulation and complex spikes, cells with irregular single-spike activity. The theta-cells were specifically related to the septal input: their reactivity to septal stimulation was higher and the latencies of their responses significantly shorter than those of the other groups of cells. Stability of the theta modulation was increased during and after septal stimulation. Reactivity to CA1 stimulation, as well as latencies of responses were identical for all groups of subicular cells. Rhythmic theta-modulation was damped after CA1 stimulation. The data indicate specific properties of the septal input to the subicular cells with theta-modulation. PMID- 4022182 TI - [Dynamics of efferent regulation of muscle contraction. Determination of transition processes: external load--muscle length]. AB - Transition processes of the length changes were studied in the ankle extensors of anesthetized cats in case of abrupt transition from isometric to isotonic condition of muscle contraction which was evoked by distributed stimulation of efferents supplied these muscles. Dynamic properties of muscles were analyzed in the framework of the two-components (inertialess and aperiodic) approximation of the transition processes. These properties were nonlinear because of the complex dependence of time constants and weight of an aperiodic component on the amplitudes of input signals. Both of these parameters were significantly lower in the shortening processes comparing with the lengthening ones. When amplitudes of length changes were small, the average limit values of the time constants were 1.38s for slow soleus muscle shortening and 0.39s for its lengthening. The same parameters for fast muscles (gastrocnemius and plantaris) were 0.55 and 0.25s, respectively. The observed dynamical properties of muscle contraction are discussed for their functional significance. PMID- 4022183 TI - [Topical organization of somatic projections to the cerebral cortex of the seal Callorhinus ursius]. AB - Somatotopic projections in the cerebral cortex of the fur seal (Callorhinus ursinus) were determined by microelectrode recordings of the multiple unit activity. Somatosensory cortical area is restricted rostrally by postcruciate and coronal sulci, caudally by anterior suprasylvain sulcus and dorsomedially by ansate sulcus. The somatotopic map in this area is oriented in such a way that the head projection is positioned ventrolaterally and that of the hindlimb dorsomedially. The projection area of the forelimb is immersed in the coronal sulcus. Marked disproportions are observed in the projections of different parts of the soma; the head projection has a relatively large magnification factor and within it the vibrissae are presented with the largest magnification. PMID- 4022184 TI - [Tonic sympathetic activity in the sciatic nerve of the rabbit]. AB - Spontaneous sympathetic activity of tibial and peroneal nerves was investigated in anaesthetized rabbits using the multichannel coherent recording technique. The tonic activity of these fibres is shown to be mainly irregular. Sometimes it correlates with the cardiac rhythm. No modulation with 10 c/s frequency described by other researchers and no respiratory modulation are observed. At constant arterial pressure the amplitude of irregular changes in the nerve activity exceeded several times the average level of the activity. PMID- 4022185 TI - [Depolarization of primary afferents evoked by cyclically modulated natural activity of proprioceptors of the hindlimb of the cat]. AB - The primary afferent depolarization (PAD) evoked during passive sinusoidal movements of a hindlimb in the ankle joint was investigated in decerebrated cats. The frequency of movements varied within 0.14-5.0 Hz, the amplitude of the joint angle with respect to the axis of the tibia changed from 90 degrees to 130 degrees. The dorsal root potential (DRP) negativity increased both during flexion and during extension of the joint. The amplitude of the evoked DRPs was about 50 100 mV. A strong negative correlation was observed between the latency and rise time of the DRP and the frequency of the joint angle changes. During flexion the latency changed from 650 ms at 0.14-0.16 Hz frequency to 100-110 ms at 2.0 Hz and higher frequencies; during extension at the same frequencies the latency changed from 300 ms to 80-85 ms. The latency and rise time became minimal at 2.0 Hz frequency and practically did not change during the further increase of the oscillation frequency. The cord dorsum potential (CDP) evoked by the cutaneous nerve stimulation was recorded in parallel with the DRP. Periodical changes of the N-component of the CDP were in the opposite phase to changes of the DRP. Mechanisms of the observed changes of the PAD and functional significance of these changes during rhythmical motor acts are discussed. PMID- 4022186 TI - [Reticular structures of the cat brain participating in startle reflexes in response to somatic stimuli of different modalities]. AB - Characteristics and reticular mechanisms of two types of late reflex responses (equivalents of the startle reflex) evoked by weak (tactile stimuli) and strong (high-threshold peripheral nerve stimulation) stimulations were studied in chloralose-anesthetized cats; these responses were designated as "tactile" (T) and "spino-bulbo-spinal" (SBS) reflexes, respectively. Some differences in the peripheral and central (brainstem) organization of these reflexes were found. In particular, the existence of the rostro-caudal differentiation of reticular structures involved in these types of reflexes was revealed using differential lesions of the brainstem reticular formation as well as its pharmacologic blockades (by means of microinjections of sodium chloride or procaine); the T reflex was found to relay mainly through the pontine RF level, while the SBS reflex--predominantly through the bulbar RF. Possible functional significance of the revealed differentiation in organization of some motor and sensory functions of the brainstem are discussed. PMID- 4022188 TI - [Proportion of short propriospinal fibers in the lumbar division of the spinal cord of the cat]. AB - Stimulating and recording electrodes were located at various distances from each other either in the lateral or in the ventral funiculus of the lumbar spinal cord of decerebrated curarized cats. The recorded response considerably decreased at the distance of 10-15 mm, suggesting that most propriospinal fibres have a length not exceeding the length of one or two spinal segments. PMID- 4022187 TI - [Responses of auditory neurons of the medulla oblongata of the frog to presentation of tones with sinusoidal amplitude modulation]. AB - The responses of single units in the medullary auditory regions of the frog Rana ridibunda to sinusoidally amplitude-modulated tones of characteristic frequencies were studied. The reproduction of the sound modulation in the discharge frequency of the units was determined from cycle histograms of the discharges locked to the modulation period. In dorsal nucleus units the amplitude modulation was preserved in the discharge modulation over a wide modulation frequency and sound intensity ranges. In many superior olivary neurons an enhancement of small amplitude changes within the range of modulation frequencies 70-150 Hz was observed. The reaction phase was linear-dependent on the modulation frequency. The best enhancement of amplitude changes took place for small modulation indices. PMID- 4022189 TI - [Activity of neurons of the motosensory cortex during natural locomotion in the cat]. AB - The activity of 42 neurons in the motosensory cortex was recorded during natural linear locomotion in two awake cats. Periodic alternations of the activity in 9 of 12 PT cells and in 13 of 30 non-PT cells were observed with respect to the locomotor cycle (modulation). The depth of the modulation of PT cells and non-PT cells was the same. The maximal-minimal activity ratio in the cycle was 16 for very modulational PT cells and was 4 for less modulational PT cells. PMID- 4022190 TI - Epidemiologic aspects of malignant skin melanoma in Slovakia. AB - The trends of age-adjusted incidence rates of malignant skin melanoma in Slovakia from 1968 to 1977 showed important increase with an annual increment of 5.8% in males and 3.2% in females. The mortality rates during this period remained lower and their increase was less expressed. The study of geographic patterns of incidence revealed great variation with highest rates in urban districts. A marked predominance of the primary lesions on trunk in males and on lower limbs in females was observed. The differences in anatomic distribution are demonstrated also in age-specific incidence rates of malignant skin melanoma by main subsites. Intermittent overexposures to the sunlight in connection with rising standard of life and leisure seem to be the most suitable explanation for the rise and subsite distribution and dynamics, as well as the geographic patterns and international position of incidence rates of malignant skin melanoma in this country. PMID- 4022191 TI - Potential anticancer agents--nitroxyl derivatives of Rubomycin. AB - Two new of the spin-labeled analogues of Rubomycin were studied. It was shown that spin-labeled derivatives were less toxic than the parent compound and had a broad-spectrum antitumor activity. Spin-labeled derivative was clearly less cardiotoxic in the rat model than Rubomycin (Daunorubomycin). PMID- 4022192 TI - Enhanced utilization of 14-methylhexadecanoic acid for the synthesis of lipids during the growth of Walker 256 carcinoma in rats. AB - Labeled 14-methylhexadecanoic acid was administered to normal rats, animals bearing the Walker 256 tumor at various stages of its growth and to tumor resistant rats and its distribution in lipids (free fatty acids, triglycerides, phospholipids and cholesteryl esters) was studied during 15 min to 3 hours following its injection in the liver, blood and tumor tissue. The period of the most active tumor growth was associated with a significantly better utilization of this fatty acid for the synthesis of lipids. The quantities of radioactive triglycerides, phospholipids and cholesteryl ester in the liver were highly increased during this time. In tumor-resistant animals the levels of radioactive lipids were similar to those in control normal animals but the turn-over of 14 methylhexadecanoic acid was considerably slower than in controls. The turn-over of the cholesteryl 14-methylhexadecanoate in the liver was significantly changed at the late stages of the tumor growth. The level of this cholesteryl ester in the blood decreased progressively during the tumor growth whereas that of triglycerides increased. No significant changes were associated with the free fatty acid and phospholipids in the blood. The total radioactivity present in the tumor increased from 0.05% up to nearly 1% of the administered 14 methylhexadecanoic acid during the growth of the Walker 256 tumor. The level of radioactive cholesteryl 14-methylhexadecanoate in the tumor tissue increased progressively during 3 hours following the injection of 14-methylhexadecanoic acid. Thus the tumor growth is apparently accompanied by significant changes in the metabolism of 14-methylhexadecanoic acid and results in an enhanced synthesis of lipids in the liver tissue. The newly synthesized lipids, in particular cholesteryl 14-methylhexadecanoate, are transported in the blood stream into the tumor where they accumulate. PMID- 4022193 TI - Flow cytometry of radiation-induced tumors in rats. AB - Hundred sixty female Wistar rats were total-body irradiated with 4 Gy gamma rays. Mammary gland tumors started to occur 8 months after irradiation, beside that also tumors of different sites appeared. By flow cytometry (FCM) 30 tumors were examined: mammary gland--22, skin--4, adrenal gland--2, liver--1, thymus--1. Eight tumors were characterized as malignant and 22 as benign. All benign and 6 malignant tumors were composed of diploid cells only. In 2 carcinomas together with diploid cells aneuploid cell lines were also found. DNA index (DI) of aneuploid cells in both carcinomas (1 mammary gland and 1 adrenal gland) indicated values of 1.66 and 1.68, respectively. Most cells of the benign and the malignant tumors occupied G1/0 (79-94%) phase of the cycle. The fraction of S (4.1-14.3%) and G2M (0.5-7.7%) cells was relatively small that suggests a low proliferative activity of radiation-induced tumors. PMID- 4022194 TI - Effects of sodium nitrite and potassium sorbate on in vitro cultured mammalian cells. AB - The food additives sodium nitrite and potassium sorbate had cytostatic and cytotoxic effects on in vitro cultured V79 hamster cells and EUE human fibroblasts if administered in an acid environment (pH 4.95). The strong cytotoxic effect of sodium nitrite and that of the combined action of sodium nitrite and potassium sorbate was observed along the inhibition of macromolecular synthesis. In this respect, potassium sorbate was less effective. The decreased plating efficiency of the cells and the inhibition of de novo DNA synthesis induced by these substances aroused the question whether they also have genotoxic effects on V79 cells. Statistical analyses showed that sodium nitrite induced more 6-TG-resistant (6-TGr) mutants as compared to the untreated control. However, this elevation did not correspond to the level of inhibition of DNA synthesis determined during the followed period of time after the removal of the substance. Potassium sorbate and a combination thereof with sodium nitrite, in our experiments, had no mutagenic effects. PMID- 4022195 TI - Giant cell formation in cultured L5178Y lymphoblasts induced by hydroxyurea treatment. AB - The conditions leading to hydroxyurea-induced abnormal cell enlargement (giant cell formation) were studied in L5178Y lymphoblasts in the culture. Exposure for only 1 hour to a concentration of 1 mM hydroxyurea (HU) was sufficient to produce an abnormal enlargement of about 25 percent of the cells. The maximal proportion of giant cells reached the value of about 50 percent after treatment with 1 mM HU for 5 hours and was not changed by a further prolongation of exposure time and/or by increasing the concentration of HU to 10 mM. Comparison of cell populations with various proportions of giant cells as regards their ability to reproduce, DNA synthesis and persistence in the culture suggested that at least some part of giant cells lost the ability to divide, their DNA synthesis was markedly suppressed or retarded and more than 50 percent of them disappeared earlier than 48 hours after the termination of HU exposure. It is concluded that at least at certain HU concentrations and in suitable stage of target cells the response of cells to short HU treatment can resemble that produced by X-rays or other DNA damaging agents. PMID- 4022196 TI - Cytogenic analysis of transplantable mouse B16 melanomas. AB - The cytogenetic analysis of transplantable in vivo melanotic and amelanotic lines of mouse B16 melanoma was performed. The second line arose by spontaneous alteration of the first one and these lines are the same in the rate of malignant growth during passages in vivo. The melanotic line shows stable near-diploid karyotype with modal chromosome number 41. The amelanotic line is mostly hypotetraploid karyotype with modal chromosome number 76. The balance of the diploids in the melanotic line is disturbed by the fact that chromosome 15 is partially trisomic, chromosome 6 trisomic, and chromosome 13 and X monosomic. Four marker chromosomes were common to both lines: M1-rob(12;12), M2-rob(5;15), M3-minute, M4-inv(1), M5-del-(14q-), but in the amelanotic line in most cases their number was doubled. Additionally, in the amelanotic line other specific aberrations rob(6;6) and rob(16;16) were observed. Both lines had comparable SCE frequencies. Constitutive heterochromatin in amelanotic line revealed the nonrandom deletion of the heterochromatic segments in chromosome 11 and, occasionally in chromosome 19. PMID- 4022197 TI - Intracellular ionic changes during hyperthermia of tumor cells in the presence of lanthanum. AB - The experimental data suggest that permeability changes at the plasma membrane level are the most likely cause of the enhancement of tumor cell killing by hyperthermia in the presence of 1 mM La3+. The interaction of La3+ with the Na+, K+ ATPase and Ca2+-pump ATPase may be the probable cause of dramatic electrolyte changes which enhance the hyperthermia effects on tumor cells. PMID- 4022198 TI - Antitumor activity of sarcolysin containing crosslinked copolymers in mice. AB - Some years ago it was found that the binding of sarcolysin to the copolymer of vinylpyrrolidone and maleic anhydride results in changes of some its pharmacological properties including toxicity, antitumor activity and immune suppression. In an attempt to keep some of this qualities of the polymeric derivatives of sarcolysin and to develop a depot-effect, sarcolysin was bonded to space linked insoluble copolymers. Studies carried out on the antitumor action in 6 transplantable tumors (L1210, P388, EAT, NK/Ly, LLC and Sarcoma 180) are discussed. PMID- 4022199 TI - [Developmental trends in neuroimmunology. 2: Specific pathogenesis, special developmental areas, concepts of therapy]. PMID- 4022200 TI - [Tandem stenoses of the cerebrovascular circulation]. PMID- 4022201 TI - [Detection of intracardiac thromboses with 111-In platelet scintigraphy]. AB - A scintigraphy with Indium-111 labelled platelets was performed in 11 patients with suspected brain embolism. In six patients, an intracardial thrombus was found: four in the region of the left ventricle and two in the left atrial. The echocardiography revealed no pathological findings in 2 of the 6 patients with positive scans. Angiography in both patients indicated occlusions of the carotis interna siphon, which frequently accompany embolisms. Subsequent angiographies four weeks later showed that the occlusions had reopened. The thrombus investigation, performed with the aid of Indium-111 platelet scintigraphy, appears to be a valuable extension of the present diagnostic potential in the determination of questionable cardial embolisms. PMID- 4022202 TI - [Fibrin degradation products and prothrombin activity in cerebral hemorrhage]. PMID- 4022203 TI - [Significance of cardiovascular risk factors for the prognosis of spontaneous intracerebral hematomas]. PMID- 4022204 TI - [Carpal tunnel syndrome in dialysis patients]. PMID- 4022205 TI - Plasma exchange in the treatment of mesangiocapillary glomerulonephritis. AB - 9 patients with primary glomerulopathies and slowly progressive renal failure were treated by regular plasma exchanges without immunosuppressive drug therapy. All 3 patients with the subendothelial type of mesangiocapillary glomerulonephritis (MCGN-I) had no progression of their renal failure while undergoing plasma exchanges. The creatinine rose when treatment was stopped and fell again in 2 patients who restarted plasma exchange. 2 patients with hypocomplementaemia and dense deposit disease (MCGN-II) and all 3 patients with idiopathic membranous nephropathy (IMN) did not benefit. 1 patient with normo complementaemic MCGN-II had some improvement in renal function which lasted 18 months. Proteinuria fell or was unchanged during the 1st month of plasma exchange in the 4 who improved and increased in the 5 who did not. The response to plasma exchanges could not be attributed to removal of circulatory complexes or changes in reticulo-endothelial function. Regular 2.8-litre plasma exchanges using 4.3% immunoalbumin proved to be safe for periods up to 44 months. Regular plasma exchange appears to prevent progression to renal failure in patients with MCGN-I. PMID- 4022206 TI - Lowered protein content of tissue fluid in patients with the nephrotic syndrome: observations during disease and recovery. AB - To find out why most patients with the nephrotic syndrome maintain a normal blood volume despite a reduced plasma colloid osmotic pressure (COP), we measured the transcapillary (plasma-tissue fluid) COP difference in 12 patients with the nephrotic syndrome, as well as in 6 patients during complete (n = 3) and partial (n = 3) recovery. Subcutaneous nylon wicks were used to collect tissue fluid. The albumin content was also measured. The albumin content and COP were lowered in both plasma and tissue fluid in the nephrotic phase, and rose gradually during recovery. During these changes the transcapillary COP difference only rose slightly: from 6.2 +/- 1.7 mm Hg when the plasma COP was below 10 mm Hg (n = 11) to 8.7 +/- 1.5 mm Hg when the plasma COP exceeded 20 mm Hg (n = 12). These observations indicate that in hypoproteinemia preservation of the intravascular volume is strongly dependent on maintenance of the difference in oncotic pressure across the capillary wall. PMID- 4022207 TI - Isolation of an immunosuppressive fraction in ultrafiltrate from uremic sera. AB - An improved purification method for isolating an immunosuppressive fraction from uremic ultrafiltrates was described. Lyophilized ultrafiltrates were fractionated on Sephadex G-15 and the active fraction was further purified using high performance liquid chromatography. The inhibitory effect of eluates on in vitro lymphocyte proliferation was assessed at the different steps of purification. Results obtained after enzyme treatment suggested that the substance(s) responsible for the immunosuppressive activity is (are) of peptidic nature. This peptide appears to be different from the other peptides previously reported, which have a much lesser activity in the lymphocyte proliferation assay. PMID- 4022208 TI - Determination of carbamylated plasma protein and its clinical application to renal failure. AB - We determined carbamylated plasma protein (CPP) according to the method of Hunninghake in patients with renal failure and normal subjects. CPP values were significantly higher in patients with renal failure than in normal subjects. In patients with renal failure, a significant correlation was found between CPP levels and blood urea nitrogen. Thus, CPP appears to be a new indicator of the status of renal failure, irrespective of hemodialysis. PMID- 4022209 TI - Sleep apnea in hemodialysis patients: the lack of testosterone effect on its pathogenesis. AB - After the discovery of sleep apnea in 2 patients receiving chronic maintenance hemodialysis, we decided to survey all 29 male patients undergoing outpatient dialysis for symptoms suggestive of sleep apnea. 12 of 29 (41%) had positive clinical histories. 8 of these patients consented to undergo all-night polysomnography. 6 were found to have sleep apnea which was primarily obstructive in type. Recent information has implicated testosterone administration in the development of obstructive sleep apnea. Therefore, polysomnography was performed in 5 of the patients both on and off weekly testosterone injections which they were receiving to stimulate erythropoiesis. There was no change in sleep complaints or a decrease in the number of apneas and hypopneas off therapy. Sleep apnea should be considered in symptomatic male dialysis patients. Its causation is presently unknown but it does not appear to be solely related to the administration of testosterone. PMID- 4022210 TI - Acute tubulo-interstitial nephritis and uveitis syndrome (TINU syndrome). AB - Acute renal failure due to tubulo-interstitial nephritis developed in a 15-year old girl. The disease was accompanied by uveitis and an inflammatory syndrome, consisting of a markedly increased erythrocyte sedimentation rate and high serum gamma globulin levels. The nephropathy as well as the inflammatory syndrome subsided spontaneously. A topical antiphlogistic treatment healed the ocular disease, which has not relapsed so far. The association of acute tubulo interstitial nephritis and acute uveitis observed in several patients has led to the identification of a specific syndrome with a very particular symptomatology and course, the so-called TINU syndrome, the interest of which resides in the predictability of the complete reversibility of the nephropathy either spontaneously or after steroid treatment, contrasting with the marked tendency towards relapse of the uveitis. The demonstration of circulating immune complexes in the serum during the acute phase of the illness, as in our patient, further points to the involvement of immune processes in the syndrome, but the origin and pathogenesis remain as yet unknown. PMID- 4022211 TI - Inhibition of platelet function by uremic middle molecules. AB - To further define the platelet abnormality responsible for uremic bleeding, we studied platelet aggregation with adenosine diphosphate, ristocetin, and collagen in serum fractions obtained by Sephadex G-15 chromatography. We found that uremic patients had considerable inhibition in several peaks of middle molecular range, but the findings were inconsistent and not clearly related to the degree of uremia. PMID- 4022212 TI - Predictive value of desferrioxamine infusion test for bone aluminium deposits in hemodialyzed patients. AB - A transiliac bone biopsy was performed in 16 hemodialyzed patients, and a staining procedure with Aluminon was used to reveal bone aluminium deposits. The baseline serum aluminium levels did not allow to predict the patients with aluminium deposits. In contrast, the peak of serum aluminium, 48 h after a desferrioxamine infusion, was much more reliable for the detection of patients with bone aluminium overload. PMID- 4022213 TI - Levamisole circumvents inhibition of lymphocyte activation imposed by uremic serum. AB - Uremic serum inhibits thymidine incorporation of phytohemagglutinin-stimulated lymphocytes originating in normal individuals. In this study the effect of levamisole on such inhibition was investigated. Preincubation with a wide range of levamisole concentrations resulted in complete prevention of the inhibitory effect imposed by uremic serum on thymidine incorporation. We would like to suggest that uremic serum possibly inhibits thymidine incorporation of normal lymphocytes by imposing an abnormal cyclic GMP/cyclic AMP intracellular ratio, and that levamisole may restore this ratio to normal. PMID- 4022214 TI - Effects of large dose vitamin E supplementation on anemia in hemodialysis patients. AB - In order to clarify the effect of vitamin E (alpha-tocopherol) on anemia and the osmotic fragility of red blood cells (RBC) plasma and RBC levels of vitamin E were measured in 30 regular dialysis patients before and after oral supplementation of vitamin E, 600 mg daily for 30 days. Plasma levels of vitamin E were in the normal range (10.67 +/- 0.85, 9.73 +/- 0.77 microgram/ml) but RBC levels in packed red cells were significantly lower than healthy controls (0.57 +/- 0.05, 0.45 +/- 0.07 microgram/ml). Oral supplementation of vitamin E increased both plasma (20.37 +/- 1.61 micrograms/ml) and RBC vitamin E (1.56 +/- 0.11 micrograms/ml) in packed red cells, while in unsupplemented patients, vitamin E levels remained unchanged. In patients receiving vitamin E, mean osmolarities at the beginning and end of hemolysis decreased from 102.8 +/- 0.9 to 98.9 +/- 0.7 and 72.1 +/- 1.1 to 67.4 +/- 0.8 mosm/l, respectively. In addition, the hematocrit increased from 26.1 +/- 1.0 to 28.1 +/- 1.2%. These changes are statistically significant (less than 0.05). In conclusion, the oral supplementation of vitamin E could be of clinical benefit in correcting anemia in regular dialysis patients by reducing the fragility of RBCs. PMID- 4022215 TI - Magnesium excretion in idiopathic hypercalciuria. AB - Given the parallelism in calcium and magnesium metabolisms, we have studied urinary magnesium in normal subjects and in patients with idiopathic hypercalciuria under conditions of basal and restricted diet, fasting, and after oral calcium overload. Serum magnesium values showed no differences between groups. Urinary magnesium levels are increased in absorptive hypercalciuria under free and restricted diet and calcium overload, returning to normal during fasting. Renal hypercalciuria patients maintain a high magnesium excretion under all conditions. This suggests that in idiopathic hypercalciuria there is an impairment of renal magnesium management, dependent on that of calcium because it normalizes when urinary calcium is normal. PMID- 4022216 TI - Oxygen uptake in exercising subjects with minimal renal disease. AB - Patients with varying degrees of renal failure were studied for their blood lactate response to exercise on either a treadmill or a bicycle ergometer. In the group exercised on a treadmill, blood lactate and alanine levels were measured, and in the group exercised on the bicycle ergometer blood lactate levels and oxygen uptake were measured. In both groups regardless of the method of exercise or the degree of azotemia, a rapid rise in blood lactate similar to that previously reported with exercise was observed. Blood alanine levels, which were low in subjects with renal disease, did not change with exercise even with a rise in blood lactate levels. There was no difference in the oxygen uptake between normal controls and subjects with renal disease. We conclude that blood alanine levels are low in renal disease, and that with the degree of exercise studied the rise in blood lactate in patients with renal disease is not accompanied by a change in oxygen uptake and does not evoke a rise in blood alanine levels. The mechanisms for the abnormal rise in blood lactate in these patients does not appear to be due to anoxia. PMID- 4022217 TI - Sequential hypertonic dialysis. AB - We have investigated the usefulness and practicability of the so-called sequential hypertonic dialysis in 2 selected patients with severe hemodialysis induced hypotension; 190 mmol/l of sodium dialysate during the 1st and 3rd h and 132 mmol/l throughout the 2nd and 4th h were used, with a Drake-Willock-Bi proportionating unit, which was electronically modified for the purpose of the study. Crossover was made, patients serving as their own controls in two consecutive cycles: 3 weeks conventional hemodialysis followed by 4 weeks sequential hypertonic dialysis, using high-flux dialyzers. At the end of sequential hypertonic dialysis a greater weight loss was achieved (p less than 0.001) with absolute stability of blood pressure. There were no significant changes in plasma osmolality and plasma volume during sequential hypertonic dialysis when compared with conventional hemodialysis. Dialysis symptoms and complications were less frequently recorded during sequential hypertonic dialysis (p less than 0.001). At the end of each sequential hypertonic dialysis period, hemoglobin, potassium, and phosphate plasma levels improved significantly and plasma sodium concentrations remained within the normal range. We conclude that sequential hypertonic dialysis is an easy and routine feasible procedure with our methodology. It is possible to achieve the ideal dry weight with no symptomatic hypotension. Sequential hypertonic dialysis constitutes an alternative to sequential ultrafiltration in selected patients, as it minimizes the falloff in plasma volume and osmolality observed during conventional hemodialysis. PMID- 4022218 TI - Sialic acid content of erythrocytes in uremic patients. Correlation with the age distribution of erythrocytes as assessed by glutamic oxaloacetic transaminase determination. AB - In a previous study we suggested that an enrichment in young red blood cells (RBC) should occur in the erythrocyte population of uremic-anemic patients. This change in RBC age distribution together with the fact that young cells were reported to be richer in sialic acid would provide an explanation for the observed lack of difference in sialic acid content between patients' and controls' whole erythrocyte populations in spite of an increased neuraminidase activity found to be present in patients' serum. To verify this assumption glutamic oxaloacetic transaminase (GOT) activity, which is an erythrocyte age index, and sialic acid were determined in low and high density fractions separated by centrifugation of packed cells representing young and old RBC, respectively, from two groups of 8 individuals with chronic renal failure and two groups of controls. GOT was determined also in whole erythrocyte populations. Mean GOT activity was significantly higher in the young fractions compared to the old of both patients' and control RBC (14.9 vs. 7.8 and 12.4 vs. 7.5 IU/g Hb). Activity of the whole RBC population was significantly higher in uremics as compared to controls (11.7 vs. 5.6 IU/g Hb) which is compatible with a lower median erythrocyte age. Mean sialic acid was higher in the young fractions as compared to the old (42.7 vs. 35.3 nmol/10(9) cells in controls and 48.9 vs. 43.0 nmol/10(9) cells in patients). These differences together with an enrichment in young cells would compensate for the eventual loss of sialic acid in the whole population resulting from an increased neuraminidase-like activity in patients' serum. PMID- 4022219 TI - Biosynthesis of methylguanidine in isolated rat hepatocytes and in vivo. AB - To clarify the organ in which methylguanidine is synthesized, high doses of creatinine, which is known to stimulate the synthesis of methylguanidine, were administered to male Wistar rats intraperitoneally. Various tissues of the rats were frozen by a freeze clamp method before and 1, 2 and 3 h after injection, and methylguanidine was determined by high-pressure liquid chromatography using 9,10 phenanthrenequinone for fluorometric determination. We found evidence that the liver, kidney, lung, muscle, red blood cells and gut flora synthesize methylguanidine. In addition, we measured the synthesis of methylguanidine in isolated hepatocytes prepared from normal rats following the addition of creatinine, arginine and guanidinoacetic acid to the incubation medium. Synthesis of methylguanidine was observed only in those incubations which contained creatinine, and was dependent on the concentration of creatinine in the media and on the incubation period. Isolated rat hepatocytes also synthesized guanidine in the presence of guanidinoacetic acid. These results indicate that the liver is one of the organs which synthesize methylguanidine and also that creatinine is the precursor. PMID- 4022220 TI - A new technique for insertion of the Tenckhoff peritoneal dialysis catheter. AB - To eliminate the discomfort caused by surgical methods and the risks involved using the trocar, for 1 year we have been using a new technique for insertion of peritoneal catheters (PC). We devised a steel instrument, vaguely resembling a rhinoscope, composed of two semicones. The handles are connected by a screw to permit dilatation of the semicones. After local anesthesia, an introducer needle is inserted into the peritoneal cavity. A guide-wire is passed through the needle which is then withdrawn and our instrument is placed around the guide and gently pushed into the peritoneal cavity. The guide is now removed and squeezing the handles of the instrument we introduce the PC up to 2 cm beyond the first Dacron cuff. When the catheter is in place, the instrument is removed and a subcutaneous tunnel may be made. We have used this method for 25 patients. 14 were new cases while 11 underwent PC repositioning. For all patients this new method proved to be excellent with practically no leakage and PC were utilized immediately or after only 24 h. We emphasize the brief time for PC insertion, the minimum discomfort and the simplicity of the technique. PMID- 4022221 TI - Plasmapheresis in a patient with rapidly progressive idiopathic IgA nephropathy: removal of IgA-containing circulating immune complexes and clinical recovery. AB - Primary IgA nephropathy is generally considered a benign disease, but progression to renal failure is not uncommon and a rapidly progressive course is observed in some cases, especially when extensive epithelial crescents are present. Circulating IgA-containing immune complexes (IgAIC) seem to play the most important pathogenetical role, hence the authors adopted plasmapheretic treatment in association with immunosuppressive drugs for 1 patient affected by primary IgA nephritis, with florid crescents and progressive renal failure. IgAIC decreased significantly after each plasma exchange and finally returned to normal values; over the same period urinary protein loss and heavy microscopic hematuria gradually disappeared and renal function was completely recovered. PMID- 4022222 TI - Diclofenac-associated acute renal failure. Report of 2 cases. AB - 2 cases of acute renal failure associated with diclofenac therapy are reported. In the 1st case no other risk factors but diclofenac administration were identified. Renal biopsy showed patchy interstitial infiltration of mononuclear cells and polymorphonuclear leukocytes. In the 2nd case preexisting nephropathy and heart failure were underlying illnesses. In both cases renal function returned to the basal values after stopping the drug. PMID- 4022223 TI - Systemic amyloidosis in the course of maintenance hemodialysis. PMID- 4022224 TI - Delayed onset of hemothorax: an unusual complication of subclavian access for hemodialysis. PMID- 4022225 TI - Pneumococcal sepsis with hemolytic-uremic syndrome in the adult. PMID- 4022226 TI - [Continuous ambulatory peritoneal dialysis in 1985: therapy of the future or impasse?]. PMID- 4022227 TI - [Use of a Tenckhoff catheter implanted in the superior vena cava in hemodialysis]. AB - For some patients in hemodialysis, repeated failure of conventional access routes requires consideration of unusual forms of access. For others, peritonitis or other problems may temporarily restrict the use of peritoneal route. We report our experience with Tenckhoff peritoneal dialysis catheter implanted into the superior vena cava through a venotomy in the right external jugular vein. The catheter was used for hemodialysis in five patients and we had no serious problems. Recirculation rate and removal rates of BUN and creatinine showed a satisfactory dialysis efficiency. While we do not recommend the procedure for routine permanent access, we believe that this technique provides a significant new choice in patients in whom conventional access methods have failed. PMID- 4022228 TI - [Creatinine clearance with low urinary output]. PMID- 4022229 TI - Plasma and myocardial catecholamine levels in young and aged rats during halothane anesthesia. AB - Plasma and heart tissue catecholamines were measured in young (4-month) and aged (28-month) Sprague Dawley rats under unanesthetized conditions and following the induction of halothane anesthesia. Arterial blood pressure, blood gases, plasma and heart tissue norepinephrine, epinephrine and dopamine concentrations were measured in separate groups of unanesthetized and halothane anesthetized rats. Young and aged rats were tested under equal anesthetic levels and blood halothane concentrations were measured using gas chromatography. Aged rats required significantly less halothane to maintain anesthesia compared to young animals (7.25 +/- 1.43 vs. 14.91 +/- 0.93 mg/dL, p less than 0.05). Cardiovascular parameters were similar in young vs. aged rats under unanesthetized conditions, but blood pressure decreased significantly more in aged than in young rats during halothane anesthesia (43% vs. 17%, p less than 0.05). Heart tissue catecholamines were not different between young and aged and did not change during halothane anesthesia. Plasma norepinephrine concentrations were consistently elevated in aged vs. young rats under both unanesthetized and anesthetized test conditions, but there was no significant change in these levels from the unanesthetized to the anesthetized state. Results suggest that increased catecholamine levels in aged animals may be necessary to maintain a normal cardiovascular state under unanesthetized conditions and that catecholamines do not increase during the hypotensive state produced by halothane anesthesia in spite of marked hypotension. PMID- 4022230 TI - Drug induced hypothermia in adult and senescent rats. AB - Temperature regulation was evaluated in senescent (34-40 month old) and adult (8 9 month old) female Iva:WIWU and Emd:Wi-AF/Han rats. Injection of 1.5 mg/kg BW apomorphine HCl or 1.0 mg/kg BW oxotremorine sesquifumarate produced comparable maximal hypothermic responses in adult and senescent rats. However, the latency to reach maximal hypothermia after oxotremorine (but not apomorphine) was longer in senescent than in adult rats of both strains. PMID- 4022231 TI - Further characterizations of the nature of the behavioral and neurochemical effects of lesions to the nucleus basalis of Meynert in the rat. AB - Converging lines of evidence indicate an important role for the basal forebrain cholinergic system in memory processes. The principal origin of the cholinergic projection to the neocortex appears to be the magnocellular neurons in the region of the nucleus basalis of Meynert (NbM). We examined the effects of bilateral lesions of the NbM on retention of shock avoidance training by stereotaxically injecting rats with 0.5 microliter of ibotenic acid (14 micrograms/microliter) into the NbM. Two weeks later rats were given passive avoidance training and tested for retention of the original avoidance habit 5 min, 30 min, or 24 hr later. Rats with lesions of the NbM showed significantly impaired shock avoidance performance compared to non-operated controls at both 30 min and 24 hr, but not at 5 min after training. Lesioned animals also showed a significant decrease in cortical choline acetyltransferase (CAT) and acetylcholinesterase (AChE) activities. No differences in muscarinic receptor binding or plasma cholinesterase activity was observed. The results demonstrate the usefulness of NbM lesions as a model for studying the role of the basal forebrain cholinergic system in memory processes. PMID- 4022232 TI - Comments on review by D.M. Gash, T.J. Collier and J.R. Sladek. PMID- 4022233 TI - Interaction of norepinephrine with Purkinje cell responses to cerebellar afferent inputs in aged rats. AB - Age-related differences in the modulatory actions of NE on the evoked activity of cerebellar Purkinje cells were examined in young (3 month) and old (18-20 month) Fischer 344 rats. We have previously shown that NE is more potent in young than in old rats, in terms of its ability to inhibit spontaneous activity. In this investigation complex spike excitation, simple spike excitation, and inhibition of Purkinje cell discharge were elicited by stimulation of climbing fibers, mossy fibers, and cerebellar parallel fibers, and quantified by computing post-stimulus time histograms of the neuronal response, recorded extracellularly. Histograms were compared before, during and after local ejection of NE from multibarreled micropipettes. In young rats NE preferentially inhibits spontaneous discharge more than evoked excitations. The inhibitory response of the Purkinje cell to activation of basket and stellate cell afferents is potentiated by NE with respect to the inhibition of spontaneous discharge. In old rats the NE-induced potentiation of both excitatory and inhibitory responses was significantly diminished. The loss of noradrenergic enhancement of the relative responsiveness of Purkinje neurons to afferent inputs in senescent animals may relate to behavioral deficits seen in aging. PMID- 4022234 TI - [Patients with multiple sclerosis among the Lodz population. I. Verification of the diagnosis and clinical characteristics]. AB - Home-treated patients with multiple sclerosis who 5-6 years earlier had sought medical advice in neurological health service institutions were examined. Their age was to 46 years; they came from the population of the City Lodz. Slightly over half of them (53%) were patients whose disease had begun at the age of 20-29 years. In 18% of cases the duration of the disease exceeded 14 years. In 60% of cases the disease had a remitting course, in 83% of them multifocal involvement of the nervous system was present. In nearly all cases (97%) pyramidal tract involvement was present, and in 59% the optic nerves were involved. Females prevailed in this group (75%); the proportion of patients aged 40-46 years was higher among the females. In males the onset of the disease before the age of 30 years was significantly more frequent, while in females the proportion of cases beginning at the age of 30-39 years was significantly greater. Among patients aged up to 40 years registered within one year by the neurologists as certain or suspected cases of multiple sclerosis (independently of the duration of the disease) about 7% patients died in a period of 5.7 years on average (10.5% males and 5.3% females). These observations suggest a different onset or course of the disease in both sexes in this population. PMID- 4022235 TI - [A method of membrane filtration of cells in the cerebrospinal fluid]. AB - The authors discuss their assessment of the technique of membrane filtration of the cerebrospinal fluid based on an analysis of over 200 cytograms obtained using Milipore membrane filters. Filtration was done in Kistler's apparatus by the method of Kistler-Bischoff and the preparations were stained with hematoxylin and eosin. In the light of the obtained results and various envisaged possibilities of use the authors recommend this condensation technique as a method of choice in cytodiagnostic examinations of the cerebrospinal fluid. PMID- 4022236 TI - [Neuropsychological evaluation of the results of treatment of hydrocephalus using a ventriculo-atrial valve]. AB - In 25 patients with hydrocephalus of various grades and aetiology treated by insertion of ventriculoatrial valves neuropsychological investigations were carried out before and after this operation using the method of Luria and certain psychometric tests. The obtained results made possible isolation of three grades of impairment of higher nervous functions: III--afunction--10 patients, II- dysfunction--12 patients, I--eufunction--3 patients. Control neuropsychological examination two weeks after the operation demonstrated improvement of higher nervous functions in 6 cases with grade III and 11 patients with grade II impairment. In these cases radiological investigations demonstrated evidence of normotensive and hypertensive hydrocephalus and this was confirmed by measurements of intraventricular pressure of the cerebrospinal fluid. In 5 cases with grades III and II of damage no improvement was found. Radiograms and measurements of intraventricular pressure suggested in these cases hydrocephalus due to brain atrophy. PMID- 4022237 TI - [Confabulation and frontal lobe injury--considerations with regard to a particular form of post-traumatic amnesia syndrome]. AB - A case of posttraumatic amnestic syndrome is described, with spontaneous confabulations as the main symptom. It is supposed that disturbances of recent memory are an indispensable, although insufficient condition for confabulation development. The author thinks that psychopathological symptoms, pathognomonic for damage to the mediobasal parts of the frontal lobes play a role in the pathogenesis of confabulations. PMID- 4022238 TI - [Syndrome of amyotrophic lateral sclerosis after thymectomy performed for myasthenic syndrome]. AB - A case of amyotrophic lateral sclerosis was observed developing three months after thymectomy in a woman aged 52 years. The patient had been referred for thymectomy because of myasthenic signs increasing in intensity since 2 years. Myasthenia was confirmed by electrophysiological investigations, and the diagnosis was: myasthenic syndrome and suspected thymoma. During nearly 5 years of follow-up the following observations were made: there was a correlation between thymectomy and the development of ALS syndrome, thymosine administration produced clinical improvement, thymosine administration improved the function of thymus-dependent lymphocytes, thymosine withdrawal (due to non-availability) produced exacerbation of symptoms. PMID- 4022239 TI - [A case of sleep apnea syndrome]. PMID- 4022240 TI - [A case of Behcet's syndrome]. AB - The author reports a case of Behcet's disease in a girl aged 18 years with recurrent lesions of the oral and vulvar mucosa, eyes and nervous system. The disease had a recurrent character with a tendency for progressing deterioration. Treatment was unsuccessful and the patient died. PMID- 4022241 TI - [Radical removal of arteriovenous angioma from the upper segment of the cervical spinal cord]. AB - A case of arteriovenous angioma of the upper part of the cervical cord is reported with discussion on the course of the disease, diagnostic methods and surgical treatment (microsurgery). PMID- 4022243 TI - [Lateral suboccipital approach to acoustic neurinomas]. PMID- 4022242 TI - [Patients with multiple sclerosis among the Lodz population. II. Clinical course of the disease and patient fitness]. AB - The motor fitness was assessed in multiple sclerosis patients remaining in their homes in the City of Lodz. The age of the patients was up to 46 years; 5-6 years earlier they had been registered within one year in neurological health service institutions after variously long periods of the disease. The proportion of those with severe motor impairment was 14%, and it was highest (17%) in the groups with disease duration 10-14 years. Nearly half of the group, independently of the age, sex and disease duration, were patients who could move about and perform household works. The proportion of fully fit and nearly fully fit was highest (83%) among those whose disease began under the age of 20 years, and it was lowest (42%) in those with disease onset at the age of 20-29 years. A tendency was observed for a different development of motor function impairment in both sexes depending on the age, age at disease onset and disease duration. In the light of the obtained results it is estimated that in the population of cities in Poland in the whole group of multiple sclerosis patients or subjects with suspected multiple sclerosis registered within one year after variously long disease duration about 40-50% remain after 5-6 years still completely or nearly completely fit. PMID- 4022244 TI - [Measurement of the normal cervical spinal cord in metrizamide CT myelography]. AB - The shape of the spinal cord is the most important factor in diagnosis of spinal disorders by metrizamide CT myelography (met. CT). Even in cases where the spinal cord looks normal in shape its size might be abnormal, for example in cases with spinal cord atrophy, syringomyelia, intramedullary tumor and several other conditions. In detecting the slightest abnormality in such cases, it is absolutely necessary to have in hand the knowledge of the normal size of the spinal cord at each level. We measured, therefore, the sagittal and transverse diameters of the cervical spinal cord in 55 patients with no known lesions on met. CT. Comparing our results with those by others, we found some differences as to the size of the spinal cord. We assume that these differences are due to the differences in resolution of the CT scanners used. The size of the spinal cord tends to measure larger with a CT scanner with high resolution than with others. Previous authors reported that the size of the spinal cord would vary by window center settings. Our experimental results indicate, however, that window center settings do not significantly affect the measurements. It is concluded that the normal values of the spinal cord dimensions at each level somewhat differ by CT equipments used. One should have normal values with one's own equipment in hand in order to take full advantage of this sophisticated diagnostic technique. PMID- 4022245 TI - [Risk factors of cerebral aneurysm re-rupture during angiography]. AB - Although re-rupture of cerebral aneurysm during angiography has been reported occasionally, we have encountered 13 such patients during eight years since 1974, the incidence corresponding to 4.4 percent of 295 consecutive aneurysm patients on whom a total of 467 angiographies were performed. Extravasation on angiogram was noticed in 10 of these patients. We carefully analyzed the following factors to determine which one is significantly related to aneurysm re-rupture during cerebral angiography. The factors we investigated were sex, age, sites of ruptured aneurysm, surgical risk grade and time interval between the latest rupture of aneurysm and angiography. Our procedures of angiography were standardized as such that contrast material was injected by means of power injector and the injection pressure was adjusted at 2.5 kg/cm2 in vertebral angiography, 3 kg/cm2 in carotid angiography and 4 kg/cm2 in retrograde brachial angiography. Volume of contrast material was 6-8 ml, 10-12 ml and 30-32 ml, respectively. An incidence of re-rupture during angiography when performed within the initial 24 hours after the latest bleeding episode was 12 out of 123 angiographies (9.8%), whereas 1 out of 344 angiographies (0.3%) which were performed later than 24 hours. This difference was significant (p less than 0.001). These data were further analyzed every one hour period. It was learned that re-rupture rate was significantly high, 9 out of 45 patients (20.0%) when angiography was done within 5 hours after the latest aneurysm rupture (p less than 0.01), particularly, 8 out of 27 patients (29.6%) within 3 hours (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4022246 TI - [Basal encephalomeningocele in an adult--a case report and clinico-anatomical classification]. AB - A 53-year-old male was admitted with complaints, of the recurrent cerebrospinal fluid rhinorrhea and meningitis. Basal encephalomeningocele was revealed by radionuclide cisternography, skull x-ray studies, and CT scan. Then, it was confirmed by operation. In reviewing the literature, we proposed a new classification of fronto-basal encephalomeningocele from clinical standpoints. 1) Anterior type; detectable facial anomalies, hypertelorism, building frontal mass or masses. Reparative operation is easy. 2) Intermediate type; no facial anomalies, cerebrospinal fluid rhinorrhea, meningitis, nasal polyp. Good results can be expected through intracranial approach. 3) Posterior type; associated many congenital anomalies such as coloboma, agenesis of the corpus callosum, and cleft palate and lip. In this type, intracranial operation has potential hazards. In our case, elevated CSF pressure due to hemodialysis for chronic renal failure may result in the late onset of CSF rhinorrhea. Etiology of 10 reported cases of the basal encephalomeningocele in Japan was also discussed. PMID- 4022247 TI - [Spontaneous extradural hematoma localized in the ventral side of the thoracic spinal cord--a case report]. AB - A case of spontaneous spinal extradural hematoma was reported. The patient, a 25 year-old housewife, was hospitalized with back pain, followed by paralysis of both legs and urinary disturbance during next 2 hours. A myelogram demonstrated that contrast medium was incompletely blocked at the level from the 3rd to the 4th thoracic spine by extradural mass. Unfortunately X-ray CT scan was not examined, however, a NMR-CT scan excluded disc protrusion and dissecting aneurysm of the aorta. Eight hours after onset, wide laminectomy was performed as emergency operation and an epidural hematoma located in the ventral side with compression of the thoracic cord was removed as completely as possible. She was discharged with excellent recovery after operation. The spontaneous spinal epidural hematoma is rare emergency. The exact etiology is unknown, and no explanation is offered as to why the hematoma is usually dorsal in location. To our knowledge, only three cases of spinal epidural hematoma which located in the ventral side were reported. Considering from our experience and other reports, it seems to be the most important point to avoid the unnecessary pressure on the spinal cord and to search the exact bleeding point in the operative procedure of ventral epidural hematomas. PMID- 4022248 TI - [A case of huge diploic epidermoid of the temporal bone with intratumoral hemorrhage]. AB - A case of huge diploic epidermoid which occurred in the right temporal bone and occupied almost all of the middle fossa and a part of the posterior fossa. CT of the tumor showed a low density lesion with multiform isodensity spots and a rim enhancement by CECT. Histologically, multiple old blood clots were recognized in this tumor contents. A review of the literature was made as regards CT findings of diploic epidermoid. PMID- 4022249 TI - [Isolated fourth ventricle simulating the Guillain-Barre's syndrome]. AB - Recently the symptoms caused by isolated dilatation of the fourth ventricle have become the subject of discussion under the name of the Isolated Fourth Ventricle (IFV). IFV is caused by occlusion of the aqueduct of Sylvius as well as the foramen of Luschka and Magendie after shunt procedure for the internal hydrocephalus, although the etiological back-ground is not fully understood yet. Most of the symptoms of hitherto reported cases are due to dysfunction of the lower cranial nerve and cerebellum. We reported an interesting adult case of IFV, whose symptoms were very much simulating the Guillain-Barre's syndrome and were completely relieved with fourth ventricle-peritoneal shunt. Clinical history was analyzed with repeated CT scans and was discussed with review of the literature. PMID- 4022251 TI - [Surgery of Craniopharyngiomas]. PMID- 4022250 TI - [Regional continuous intraarterial infusion of urokinase in the acute stage of cervical and intracranial major artery occlusion--particularly on a case of successful improvement after therapeutic recanalization]. AB - We recently applied regional continuous intraarterial infusion of urokinase (UK) for five cases suffering from occlusion of the cervical and intracranial major arteries within nine hours from the onset to the start of infusion. In this paper we reported mainly about a 55-year male patient of occlusion of the left cervical internal carotid artery, which was recanalized by regional continuous intraarterial UK infusion, with discussion about the manipulation of UK infusion, indication of patient and management after recanalization. PMID- 4022252 TI - [Fontanelle pressure in infants (Part II). Discussion on 6 cases of macrocrania]. AB - From the results of ICP determination in 6 cases of macrocrania, it is evident that Lundberg's pressure wave (plateau wave, B wave) can be sufficiently adapted for evaluating abnormality under the semi-closed circumference like infants. ICP determination in the case of macrocrania with mild enlarged ventricles important for knowing pathologic changes. In particular, pressure variation and amplitude changes during REM period seem to be an interesting index for knowing the involvement of venous function. The increased ICP during REM period was also observed in a patient with holoprosencephaly having brain stem formation only, suggesting an important relationship between brain stem and increased ICP during REM period. PMID- 4022253 TI - [Study of ruptured intracranial aneurysms with intracerebral hematomas--with special reference to operative indication]. AB - We reviewed 40 cases of intracranial ruptured aneurysm with intracerebral hematoma (An-ICH) and compared those with 177 cases of intracranial single ruptured aneurysm causing only subarachnoid hemorrhage (An-SAH). An-ICH accounted 11.6% of the intracranial aneurysm, ruptured at the mean age of 54 years, and occurred equally in both sexes. The localization of An-ICH was 50% in the middle cerebral artery (MC), 43% in the anterior cerebral artery (AC) and 8% in the internal carotid arterial region. Forty percent of An-ICH were treated conservatively and the outcome was very misery (no useful life and 94% was poor or dead). Sixty percent of An-ICH were treated surgically (neck-clipping and removal of the hematoma) and the outcome was poor (17% useful life and 46% poor and dead). Especially in MC aneurysm, operability was 85% and post-operative useful life was 12% and post-operative poor or dead was 53%. In AC aneurysm, operability was 35% and post-operative useful life was 33% and poor or dead was 33%. These miserable results raised a question of operative indication for An ICH. The five clinical indices (decerebration, hypertension greater than or equal to 200 mmHg, Hunt-Hess grade V, anisocoria in AC, severe shift of midline structure on X-CT) were selected, because any patients who presented with even only one of them became fatal or vegetative state regardless of conservative or surgical treatment. Assuming them as the non-operative standards, operability decreased in 35% MC, 29% AC, useful life outcome came up to 20% MC, 40% AC, and misery outcome came down to 20% MC, 20% AC.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4022254 TI - [Squamous cell carcinoma of the frontal sinus caused osteomyelitis of the frontal bone]. AB - A case of the squamous cell carcinoma of the frontal sinus complicated with osteomyelitis of the frontal bone was reported. A 47-year-old male was admitted to Asahikawa Medical College Hospital because of a bulging of forehead and remittent fever of a six-month history and general convulsive seizures on the day before admission. On physical examination, a bulging of forehead with redness, tenderness and fluctuation was noted. Sense of smell diminished bilaterally. Oto laryngological examination disclosed paranasal sinusitis. Skull X-P and CT scan suggested osteomyelitis of the frontal bone secondary to frontal sinusitis. However, a frontal sinus tumor with osteomyelitis was also possible. Operation was performed and a granulomatous mass attached to the dura with thick epidural abscess was noted. The mass and affected bone edge were removed. Pathological examination of the specimens disclosed findings of squamous cell carcinoma and osteomyelitis. Recurrence of the tumor rapidly occurred and reoperation was performed a month after the first operation. Postoperative irradiation and chemotherapy with pepleomycin were done but failed to control the growth and recurrence occurred immediately. The tumor penetrated the skin of the forehead and the patient died of cachexy 7 months after the first surgery. Osteomyelitis usually occurred in the metaphysis of long tubular bone and rarely in short bone or flat bone such as a skull. This is attributed to the difference of distribution of the bone marrow vessels. Embolization and subsequent growth of bacteria in the blood flow is less liable to occur in short bone and flat bone.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4022255 TI - [Trigeminal neurinoma presenting abducens nerve palsy as initial symptom: a report of two cases]. AB - Two cases of trigeminal neurinoma presenting abducens nerve palsy as initial symptom are reported. Case 1. A 33-year-old female was admitted because of double vision of two months duration. Neurological examination revealed left abducens nerve palsy. CT scan disclosed a left parasellar tumor with a homogeneous enhancement effect. The tumor was subtotally resected by left extradural subtemporal approach, and diagnosed as trigeminal neurinoma. Case 2. A 18-year old female was admitted because of double vision of one month duration. Neurological examination revealed left mydriasis and left abducens nerve palsy. CT scan disclosed a low density mass in the left cerebellopontine angle region and enhanced parasellar mass. The cystic mass located at the posterior fossa was removed by left retromastoid suboccipital approach, and diagnosed as trigeminal neurinoma. In these two cases, the abducens nerve palsy disappeared within two months postoperatively. The trigeminal neurinoma presenting abducens nerve palsy as initial symptoms is rare. We were able to collect six similar cases from the literature. All of them, including present two cases, were classified as ganglion type. It was suspected that the abducens nerve was compressed by the trigeminal neurinoma at the cavernous sinus, the petrous apex or the posterior fossa. PMID- 4022256 TI - [Intracranial chordoma--report of two cases with cytochemical study]. AB - Intracranial chordoma is very uncommon. We report two cases of intracranial chordoma with cytochemical studies. Case 1: A 66-year-old housewife was admitted on February 10, 1981, complaining of disturbance of visual acuity and bitemporal hemianopsia. A plain skull film showed normal finding with no calcification. CT showed a spherical ring contrast enhancement with intraluminal low density area in the suprasellar cistern. Pneumoencephalogram showed a suprasellar mass with filling defect of the anterior part of the third ventricle. On February 28, 1981, the tumor was intracapsually removed by transfrontal approach. The tumor had re brown-turbid fluid. On March 16, she was discharged with no disturbance of visual acuity and visual field. But she again complained of visual disturbance and was hospitalized on October 26, 1981. Second operation was performed through trans frontal route. The tumor with pus-like fluid was resected subtotally and postoperative radiation was given with 4,500 rads. Histologically the tumor had physaliferous cells cytomorphologically. Cytochemical study: cytoplasm and matrix were detected positively with PAS stain, Mucicarmine stain, Alcian blue stain, and Colloid-Iron stain. Mucinous glycogen was positive by PAS stain after diastase digestion test. These mucinous material was not stained with Sudan stain. Case 2: A 36-year-old man was admitted with paresthesia on right lower face on September 27, 1983. In the past history he complained of diplopia for several months in 1978 and 1982. A tomography of the skull showed a spherical soft mass in the sphenoid sinus and a calcified lesion from the posterior clinoid process to the floor of the third ventricle.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4022257 TI - [Ruptured cerebral aneurysm of the median artery of the corpus callosum (accessory anterior cerebral artery): case report]. AB - A rare case of ruptured cerebral aneurysm of median artery of corpus callosum (accessory anterior cerebral artery: Acc ACA) is reported. A 66-year-old hypertensive female suddenly lost consciousness for 5 minutes and later complained of severe headache. On admission, the next day, consciousness was clear and she showed no neurological deficit except for right motor weakness. CT scan revealed subarachnoid hemorrhage, and carotid angiography showed triplicated anterior cerebral artery with a saccular aneurysm on the Acc ACA. Twenty hours after the onset, an operation was performed to clip the aneurysm neck. Post operative course was uneventful and she was discharged on the 25th postoperative day without neurological deficits. When the median artery of corpus callosum(MACC), a branch of anterior communicating artery distributes to one or to both hemispheres, it is called Acc ACA. It is thought to be a vascular anomaly and which has an incidence of 20%. However, cases of aneurysm of MACC (or Acc ACA) have not been reported and our case is considered to be the first. PMID- 4022258 TI - Glycogen particles in methionine sulfoximine epileptogenic rodent brain and liver after the administration of methionine and actinomycin D. AB - Rats and mice were submitted either to the convulsant methionine sulfoximine (MSO) alone or to MSO combined with actinomycin D or methionine respectively. Twenty-four hours after the intraperitoneal administration of these compounds, the animals were killed and tissue samples were prepared for electron microscopy. Methionine sulfoximine induced 'grand mal' type seizures which were abolished by methionine. In saline controls, glycogen was as beta particles located in the cytoplasm of astrocytes, i.e. in perikarya and processes. Liver glycogen was as perinuclear masses of alpha and beta particles or as alpha particles scattered in all the cytoplasm. When the rodents were treated with MSO, glycogen was as alpha and beta particles which invaded all areas of the astrocyte cytoplasm, this increase being tremendous in perivascular end feet. Actinomycin D slowed down the accumulation of glycogen particles while methionine completely abolished it. In any case, glycogen particles were confined to the astrocytes and were never seen in other types of cells. In liver, MSO induced an important decrease or a complete disappearance of glycogen particles. When the convulsant was combined with actinomycin D or with methionine, the figures looked like those of controls. These results have been discussed in relation to the mechanism of glycogenesis in central nervous system of rodents submitted to MSO. PMID- 4022259 TI - A cerebellar abnormality in the mouse with motor end-plate disease. AB - The murine mutant with motor end-plate disease (med) exhibits a progressive weakness which is due to a functional denervation of skeletal muscle. It is inherited as an autosomal recessive trait and has two alleles. One of these is the jolting (medjo) mouse which also suffers from a disturbance of locomotion. Although the jolting animal was originally thought to suffer from a disorder of neuromuscular transmission, the organization of the peripheral nervous system is indistinguishable from normal and neuromuscular transmission is unimpaired. It is now clear that abnormalities in the cerebellum are responsible for the gait problems of the jolting mouse, and a preliminary morphological and neurophysiological examination of the mouse with motor end-plate disease has shown that it also has cerebellar abnormalities. Axonal spheroids may be seen on cerebellar Purkinje cell axons in the med mouse, and the character of extra cellular recordings obtained from the Purkinje cells is abnormal. PMID- 4022260 TI - Distribution and release of immunoreactive thyroid-stimulating hormone in the rat hypothalamus: effects of thyroidectomy, hypophysectomy and treatment with thyroid hormones. AB - Immunoreactive thyroid-stimulating hormone (IR-TSH) has been detected in the hypothalamus and is released in vitro by a calcium-dependent mechanism when the tissue is depolarized. Recently, immunocytochemical studies have revealed that IR TSH is present in thyrotropes in the pars tuberalis. Therefore, because these thyrotropes are associated with the median eminence, the area with the highest concentration of IR-TSH, it is of interest to determine if 'hypothalamic' IR-TSH is from neural or pituitary cells. We addressed this issue by studying the effects of hypophysectomy, thyroidectomy, or chronic administration of triiodothyronine (T3) or thyroxine (T4) on the distribution and in vitro release of IR-TSH in the hypothalamus. We reasoned that, if hypothalamic IR-TSH is dependent on the thyrotropes of the pars tuberalis, then changes in hypothalamic IR-TSH concentration and release should be parallel to those measured in pituitary extracts. IR-TSH was measured in tissue extracted in ice-cold 2% NaCl, with a final pH of 4.5. For the in vitro studies, tissues were incubated for 20 min periods in Krebs-Ringer bicarbonate buffer at 37 degrees C. In untreated rats, the concentration of IR-TSH is greater in the ventral than the dorsal portion of the hypothalamus (39.3 +/- 8.2 vs. 4.0 +/- 1.5 ng/mg wet wt.). Upon finer dissection of the hypothalamus into median eminence and anterior, middle, and posterior portions of the remainder, IR-TSH was only detectable in the middle hypothalamus (5.3 +/- 1.5 ng/mg), and the median eminence (149 +/- 41 ng/mg).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4022261 TI - Serum melatonin response to melatonin administration in the Syrian hamster. AB - Chronic daily administration of melatonin (MT) can have potent effects on reproduction in the hamster. Various theories have been elaborated to explain these effects but little information has been available on circulating levels of MT following MT administration. We have examined the serum MT response in the male hamster to a single dose of 25 micrograms MT administered in the morning or in the afternoon--the same timing and dose used by others to produce reproductive effects. With both morning and afternoon administration, serum MT increased above 1,000 pg/ml and remained above the highest basal levels during most of the 24 hour cycle. These levels are clearly supraphysiologic ones. The decline in serum MT showed two distinct components following morning administration. Half-life of the initial component which probably represents rapid distribution into tissues was 17.3 min. A half-life of 25.1 h was calculated for the second component. We conclude that use of a 25-micrograms dose of melatonin to study pineal effects may be misleading. PMID- 4022262 TI - Effect of frontal hypothalamic deafferentation on photoperiod-induced changes of luteinizing hormone secretion in the ewe. AB - These experiments were conducted sequentially in two parts. In the first, we examined the effect of frontal hypothalamic deafferentation (FHD) on photoperiod induced changes in luteinizing hormone (LH) concentration in ovariectomized ewes ('steroid-independent' changes). In the second we placed Silastic implants of estradiol-17 beta in these same ewes and examined the effect of FHD on photoperiod-induced changes in the LH concentration in the presence of estradiol ('steroid-dependent' changes). 15 ovariectomized Suffolk ewes were subjected either to FHD (n = 10) or sham FHD (n = 5). They were placed in a photochamber and exposed to the following lighting regimens. In the first part, two trials of alternating lighting periods were used: trial 1 = 120 days of 8 h light (L):16 h dark (D) followed by 90 days of 16L:8D; trial 2 = 90 days of 8L:16D followed by 60 days of 16L:8D. In the second part, three lighting periods of alternating daylengths were used: 65 days of 16L:8D, followed by 60 days of 8L:16D and by 60 days of 16L:8D. Blood samples were collected from the jugular vein at 20-min intervals for 3 or 4 h during the last day of each lighting period. Data on mean LH concentrations were obtained. The location of the FHD was verified histologically. In the absence of gonadal steroids, 16L:8D increased, whereas 8L:16D decreased the LH concentration (p less than 0.001) in both sham FHD and FHD ewes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4022263 TI - Myoclonus in the rat induced by p,p'-DDT and the role of altered monoamine function. AB - Administration of p,p'-DDT to rats produced myoclonus, but unlike previous studies in mice, this was not decreased by administration of clonazepam. Precursors of 5-hydroxytryptamine (5-HT) (L-tryptophan and L-5-HTP) reduced the intensity of myoclonus, but the 5-HT agonists, quipazine and Org 6582 did not. Antagonists of 5-HT (methergoline, methysergide and cinanserin) did not potentiate the myoclonus induced by p,p'-DDT. Drugs altering the function of dopamine and noradrenaline (apomorphine, clonidine or phenoxybenzamine) also had no effect on this myoclonus. Administration of monoamine oxidase inhibitors (MAOIs; pargyline, nialamide and tranylcypromine) markedly attenuated the myoclonus, an effect that could not be attributed to an action on any one monoamine system. No observable changes in cerebral biochemical parameters of 5 HT occurred at the onset of myoclonus, although tryptophan and 5 hydroxyindoleacetic acid (5-HIAA) in brain were increased following periods of prolonged myoclonus. Electrophysiological analysis of the myoclonus in the rat induced by p,p'-DDT revealed changes in EEG and EMG activity which suggested an origin for the myoclonus in the brainstem. Although this was similar to electrophysiological findings in some human patients with post-anoxic action myoclonus, the pharmacological studies suggest that the myoclonus induced by p,p' DDT in the rat is not a suitable model for screening potential drugs to be used in the treatment of this disorder. PMID- 4022264 TI - S(+)Apomorphines. Selective inhibition of excitatory effects of dopamine injected into the limbic system of the rat. AB - Dopamine (DA) injected unilaterally into the corpus striatum of the brain of the rat after pretreatment with a monoamine oxidase inhibitor, induced contralateral deviation of the head (ED50 = 23 micrograms). Dopamine, administered similarly into the nucleus accumbens septi, induced strong locomotor arousal effects (ED50 = 32 micrograms), as reported by others. Systemic administration of the S(+) isomers of apomorphine (APO) and its N-n-propyl analog (NPA) had no significant action on the effects on posture of DA given intrastriatally, even in large doses. In striking contrast, both agents selectively inhibited the locomotor arousal effects of DA injected into the accumbens, but (+)NPA was seven times more potent (ED50 = 0.5 mg/kg vs 16 micrograms of DA) and its effects lasted for about 70 min. The dose-effect curves for (+)NPA against two doses of DA demonstrated parallel, lateral displacement, indicating a competitive interaction. These results support the impression that enantiomers and analogs of apomorphine, and especially S(+)N-propylnorapomorphine, have potent antidopaminergic actions that may be selective for limbic areas of the forebrain. PMID- 4022265 TI - Aluminum alters the permeability of the blood-brain barrier to some non-peptides. AB - The effect of aluminum administered intraperitoneally (i.p.) on the levels of peripherally injected 99mTc labelled red blood cells in brain and on the penetration of the blood-brain barrier by radioiodinated serum albumin (RISA), thyroxine, iodide, cortisol, N-Tyr-delta sleep-inducing peptide (N-Tyr-DSIP), growth hormone, thyroid stimulating hormone (TSH), prolactin and human and rat luteinizing hormone was examined. Treatment with aluminum did not alter the brain/blood ratio for either 99mTc red blood cells or RISA, although it did increase the blood levels of RISA. These results show that aluminum caused a contraction in the volume of plasma without altering the vascular space of the brain, disrupting the blood-brain barrier, or increasing the "leakiness" of the blood-brain barrier. Aluminum enhanced the permeability of the blood-brain barrier to labelled prolactin, thyroxine, cortisol, growth hormone, N-Tyr-DSIP and rat luteinizing hormone, but not to labelled TSH, iodide, or human luteinizing hormone, a substance with an octanol coefficient markedly different from that of luteinizing hormone from the rat. Incubation of the peptide with aluminum before injection did not increase penetration, demonstrating that aluminum did not increase the permeability of the blood-brain barrier by acting directly on the peptide. Aluminum, administered intraperitoneally, increased the accuracy of lipophilicity as a predictor of penetration of the blood-brain barrier, but the greatest increase in penetration was seen with thyroxine, a substance which crosses the blood-brain barrier by carrier-mediated transport.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4022266 TI - Effects of a depressant/convulsant pair of glutarimides on neuronal activity in the isolated spinal cord of the immature rat. AB - The effect of depressant/convulsant pair of glutarimides on the isolated spinal cord of the immature rat was examined using extracellular recording. At concentrations of 300 microM the depressant beta-butyl-beta-methyl glutarimide enhanced the response of motoneurones and dorsal root fibres to gamma aminobutyric acid (GABA) while the convulsant bemegride (beta-ethyl-beta-methyl glutarimide) decreased both responses to GABA. At this concentration both the convulsant and depressant reduced mono- and polysynaptic reflex activity. Neither the convulsant or depressant had prominent direct actions, with only a small hyperpolarization being produced by both glutarimides on dorsal root fibres. The overall depressant or convulsant properties of these glutarimides may be due in part therefore to a differential effect on the postsynaptic action of the inhibitory transmitter GABA. Furthermore, the depressant glutarimide reduced the excitatory effects of L-glutamate and the convulsant reduced the inhibitory effects of glycine on spinal neurones; thus, actions on these transmitters may also contribute to the overall effects of these glutarimides. PMID- 4022268 TI - Cross tolerance between ketamine and morphine to some pharmacological and biochemical effects. AB - Whether morphine and ketamine induced cross-tolerance to some of their common pharmacological and biochemical effects, namely analgesia and enhancement of metabolites of dopamine (DA) in the striatum and limbic area of the rat was analysed. Ketamine was given at the dose of 100 mg/kg, twice a day for 8 days. After this treatment, a challenge dose of morphine (15 mg/kg, i.p.) still induced analgesia comparable to that induced by morphine alone, showing no cross tolerance to this effect. In contrast, the challenge dose of morphine given to ketamine-tolerant rats no longer enhanced metabolism of DA, indicating the appearance of cross-tolerance to this effect. A high degree of tolerance to morphine was obtained after the subcutaneous implantation of rats with pellets of morphine; a challenge dose of ketamine to morphine-tolerant rats induced marked analgesia, with no cross-tolerance to this pharmacological effect, while cross tolerance was present to the biochemical effect. The existence of a high degree of reciprocal cross-tolerance in both areas and on both metabolites of DA is consistent with the hypothesis of action at a common receptor; the lack of cross tolerance to the analgesic effect indicates that analgesia is achieved by a different mechanism for the two drugs. PMID- 4022267 TI - Exposure to nicotine enhances the behavioral stimulant effect of nicotine and increases binding of [3H]acetylcholine to nicotinic receptors. AB - Rats were given daily injections of nicotine sulfate in doses ranging from 0.1 to 0.4 mg/kg. The behavioral effect of these injections was measured as locomotor activity in photocell cages. Repeated administration of the same dose to each rat resulted in an enhancement of the stimulant effect of nicotine. This enhanced behavioral effect was quite pronounced within 5 days of repeated injection. Tissue from the cerebral cortex of these rats, exposed to nicotine for 5 days, was assayed for binding of [3H]acetylcholine to nicotinic receptors. These relatively small doses of nicotine resulted in 18-26% increases in cortical nicotinic receptors, compared to saline-treated rats. Rats exposed to 0.2 mg/kg of nicotine for 5 days and then given saline for 7 days still showed an enhanced behavioral response to nicotine on the eighth day after exposure, and nicotinic binding in the cortex was still elevated. However, 21 days after exposure to nicotine both the behavioral response to nicotine and the binding values had returned to the same values as those of saline-treated rats. These data imply that increased binding of [3H]acetylcholine to nicotinic sites and the enhanced behavioral effect of nicotine are functionally linked. PMID- 4022269 TI - Lack of effect of 1-methylisoguanosine on sleep in rats. AB - The dose-response effects of intracerebroventricular (i.c.v.) administration of 1 methylisoguanosine (MIG) on sleep in rats were examined. Not even the largest dose (100 nmol/rat) of 1-methylisoguanosine produced significant hypnotic effects, whereas doses of 10 and 100 nmol/rat suppressed rapid eye movement sleep in rats. The only statistically significant effect of 1-methylisoguanosine on sleep latencies was an increase in the latency of S2 after intracerebroventricular administration of 100 nmol/rat of the drug. These effects of 1-methylisoguanosine on sleep were unlike those of both adenosine and the benzodiazepines, suggesting that, contrary to earlier speculations, 1 methylisoguanosine does not interact with central adenosine or benzodiazepine receptors. PMID- 4022271 TI - Electrophysiologically recorded C-fiber reflexes in intact and acute decerebrate spinal cats: absence of naloxone facilitation in intact cats. AB - A C-fiber reflex was obtained from stimulating and recording electrodes attached respectively to the superficial peroneal and posterior biceps semitendinosus nerves in intact cats. Naloxone in a dose dependent manner increased vocalizations produced by nerve stimulation, but it did not facilitate the C fiber reflex in the intact cat. However, naloxone facilitated C-fiber reflexes in decerebrate-spinal cats under identical stimulating and recording conditions as used in the intact cat. It was concluded that naloxone causes increased nociception to cutaneous nerve stimulation in intact cats but for naloxone to facilitate the C-fiber reflex, removal of supraspinal control is necessary. Many C-fiber afferents transmit nociception to the CNS (Bessou and Perl, 1969). Electrical stimulation of the superficial peroneal nerve that activates C fibers produces a segmental reflex in the unanesthetized decerebrate-spinal cat (Koll, Hasse, Schutz and Muhlberg, 1963). This C-fiber reflex is manifested by a long latency discharge recorded from an ipsilateral L7 or S1 ventral root. The C-fiber reflex is considered nociceptive because only intense stimulation evokes it and morphine depresses it in doses lower than those that depress other spinal reflexes (Koll et al., 1963). Low doses of the opiate antagonists naloxone and naltrexone consistently facilitate the C-fiber reflex (Bell and Martin, 1977). These results support the hypothesis that released endogenous opioids inhibit the C-fiber reflex. However, the facilitative effects of the opiate antagonists could be confined to the decerebrate-spinal preparation where invasive experimental procedures (decerebration, dissection, etc.) may release endogenous opioids.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4022270 TI - Effects of bath-applied GABA on the firing pattern of cells in an in vitro preparation of mammalian cerebral cortex. AB - The patterns of spontaneous firing recorded from 25 cells in slice preparations of rat cerebral cortex were characterised using inter-spike interval plots (ISI). Histograms of the ISI showed two peaks having modal values of 20 and 82ms, corresponding to episodes of high frequency bursts of action potentials, and a lower frequency, steady pattern of activity. Bath-applied GABA was shown to reversibly block the bursting activity, but had little effect on the lower frequency component. This effect of GABA could be abolished by the simultaneous application of bicuculline. PMID- 4022272 TI - Epileptogenic action of penicillin derivatives: structure-activity relationship. AB - In the hippocampal slice preparation, perfusion with benzyl penicillin evokes multiple population spikes and spontaneous discharges. Doses of 0.25 to 2 mM of the drug produced this effect within 20-40 min. Cleavage products and analogues of benzyl penicillin, penicilloic acid, 6-aminopenicillanic acid, cephalexin, thioproline and penicillamine, were devoid of such action. It is concluded that the structural requirements for epileptogenic action of penicillin include not only the beta-lactam ring and side chain substitution on C-6, but also the thiazolidine ring. PMID- 4022273 TI - Opiates and opioid peptides modify sensory evoked potentials and synaptic excitability in the rat dentate gyrus. AB - The effects of morphine and the synthetic opioid peptide D-Ala2-MePhe4-Met-O-ol enkephalin (FK 33-824) on averaged (AEPS) potentials evoked by a tone and extracellular synaptic potentials (EPSs) in the perforant path, recorded from the outer molecular layer (OM) of the dentate gyrus, were examined in rats trained to respond in an auditory discrimination task. Potentials evoked by a tone were systematically altered by both peripheral (intraperitoneal) and central (intracerebroventricular) administration of opioids. The short-latency negative (N1) component of the average evoked potential was increased in amplitude and the longer-latency negative (N2) component was decreased in amplitude by administration of opioids. At the same time, perforant path extracellular synaptic potentials were enhanced after administration of opioids. The changes in the average evoked potential and extracellular synaptic potentials in the perforant path were reversed by subsequent administration of naloxone. The significance of these results is discussed in terms of a possible role of endogenous opioid peptides in modulating the synaptic efficacy of the perforant path during the transmission of sensory information to the hippocampus from the entorhinal cortex. PMID- 4022274 TI - Adenosine antagonists. Lack of effect on the inhibition of kindled seizures in rats by carbamazepine. AB - This study investigates the ability of adenosine antagonists to reverse the anticonvulsant effects of carbamazepine on amygdala-kindled seizures in order to elucidate the possible physiological relevance of the potent effects of carbamazepine on adenosine receptors. At large but subconvulsant doses, neither caffeine nor theophylline altered the anticonvulsant potency of carbamazepine, even though caffeine by itself significantly increased the duration of the kindled afterdischarge. The adenosine agonist cyclohexyladenosine (CHA), administered intraperitoneally at a dose that produced sedation, had no effect on the kindled seizures. Although carbamazepine potently displaces the binding of several adenosine ligands in vitro, the present data do not suggest that the anticonvulsant effects of carbamazepine on amygdalakindled seizures are mediated by an adenosine agonist-like action. PMID- 4022275 TI - Adrenalectomy attenuates stimulation-produced analgesia. AB - Ablation of the adrenal glands potentiates analgesia induced by morphine and attenuates an opioid form of stress-induced analgesia. the adrenal cortex has been implicated in analgesia induced by morphine and enkephalin-like peptides in the adrenal medulla have been suggested to modulate stress-induced analgesia. The effect of adrenalectomy upon analgesia produced by stimulation of the brain has not been investigated. The present investigations demonstrated that antinociception (measured with the tail-flick test) from focal stimulation of the periaqueductal grey was attenuated or abolished after adrenal ablation. These results implicate adrenal hormones in the regulation of the endogenous pain inhibitory system in the brain. PMID- 4022276 TI - Comparison of imipramine-imipraminium in mice. To elucidate central or peripheral origin of effects of imipramine. AB - Imipramine hydrochloride shows effects in a battery of tests used for the screening of antidepressant drugs. The central origin of these pharmacological effects of imipramine has not been clearly established. Imipramine methiodide is a quaternary derivative of imipramine which does not cross the blood-brain barrier easily. The effects of the two forms of imipramine have been compared: on an effect known to have a central origin; on two effects known to have a peripheral origin; on a battery of tests used for the screening of antidepressant drugs. It has been demonstrated that imipramine methiodide is as active as imipramine hydrochloride on two effects of peripheral origin, less active than imipramine hydrochloride on an effect considered to have a central origin and less active than imipramine hydrochloride or inactive on the tests which are used for the screening of antidepressant drugs. Consequently, the tests used for the screening of antidepressant drugs represent, primarily or exclusively, effects of central origin. PMID- 4022277 TI - Interaction between the baroreflex and anterior hypothalamic stimulation. Demonstration of a noradrenergic involvement. AB - Cats, anaesthetized with alpha-chloralose, were used to investigate an interaction between the baroreceptor reflex and stimulation of the anterior hypothalamus (AH). In these cats, stimulation of the anterior hypothalamus gave autonomic responses that characterize the defense reaction. Stimulation of the anterior hypothalamus also interacted with the baroreceptor reflex without altering the effectiveness of the vasodepressor component of the reflex (induced by stimulation of the aortic nerves). However, in spinal cats the bradycardia component (induced by angiotensin at 0.097 nmol/kg pe min, i.v.) was inhibited by stimulation of the anterior hypothalamus and the inhibition was augmented by pretreatment with phentolamine (17.7 nmol) in the nucleus tractus solitarius (NTS). Pretreatment with phentolamine (17.7 nmol) in the nucleus tractus solitarius also reduced the sensitivity of the bradycardia component of the reflex and attenuated (3 and 6 nmol) the induced inhibition of the bradycardia induced by stimulation of the anterior hypothalamus. This attenuation induced by NE was abolished by pretreatment with phentolamine (17.7 nmol), but not by pretreatment with sotalol (16 nmol) or haloperidol (12 nmol) in the nucleus tractus solitarius. Additionally, NE was released from the nucleus tractus solitarius during activation of the baroreceptor and during stimulation of the anterior hypothalamus in cats with intact baroreceptor nerves, but not in baroreceptor-denervated cats. Moreover, the baroreceptor reflex attenuated the pressor response evoked by stimulation of the anterior hypothalamus, and also caused the release of NE from the anterior hypothalamus. At this site, injection of NE (3 and 6 nmol) attenuated the pressor response evoked by stimulation of the anterior hypothalamus and this attenuation was abolished by pretreatment with phentolamine (17.7 nmol), but not by pretreatment with sotalol (16 nmol) or haloperidol (12 nmol) in the anterior hypothalamus. It is concluded that NE participates at the nucleus tractus solitarius and the anterior hypothalamus as an attenuator in the interaction between the baroreflex and stimulation of nerve fibers in the anterior hypothalamus that mediate the defense reaction. PMID- 4022278 TI - Stability of the amino acid content of nerve endings after administration of gamma-aminobutyrate agonists and antagonists. AB - The administration of GABA agonists or antagonists to mice resulted in unchanged levels of aspartate, glutamate, GABA and taurine in nerve endings (synaptosomes). On the other hand, agonist-induced increases in the levels of some of the amino acids occurred in locations other than the nerve endings. The GABA agonist SL75102 inhibited in vitro uptake of D-aspartate into synaptosomes, thereby raising the possibility that a similar phenomenon may cause an in vivo redistribution of glutamate and aspartate in brain tissue. PMID- 4022279 TI - The subcellular distribution of peptides immunoreactive for the carboxyl-terminal extension of cholecystokinin in rat brain. AB - An antiserum raised against a synthetic peptide (D-10-Y) comprising the carboxyl terminal extension of cholecystokinin (CCK) detects several immunoreactive peptides, which were found to be widely distributed in rat brain (1). This article reports the subcellular distribution of these D-10-Y-like immunoreactive peptides in whole rat brain. Primary subcellular fractionation yielded a mitochondrial (P2) and microsomal (P3) fraction, both of which were enriched in D 10-Y and CCK 8 peptide immunoreactivity. Further fractionation of P2 yielded a purified synaptosome fraction (P4) which was further enriched in D-10-Y and CCK 8 like peptides. Whole rat brain contains two major molecular forms of D-10-Y-like immunoreactivity, one similar in size to CCK 33 (peak 1) and one slightly larger than CCK 8 (peak 2). In the P2 and P3 fractions, most of the D-10-Y-like immunoreactivity was similar in size to peak 2. It is likely that this D-10-Y like immunoreactive peptide is an intermediate in the processing of CCK 8, and its enrichment in nerve endings is consistent with the final cleavage and amidation reactions taking place in the nerve terminals. PMID- 4022281 TI - Neuropeptides differentially effect various forms of morphine tolerance. AB - Two different forms of tolerance to morphine were shown to develop. One form, environment dependent (ED), was associated with cues paired with the arrival of the drug. The second form of tolerance, environment independent (EI), was not dependent on any cues. ED tolerance was induced using a multiple injection model in which a cue (orange scent) preceeded each morphine injection (ip). After 12 days the animals were tolerant to the i.p. injection. However if morphine was injected i.c.v. tolerance was no longer evident. EI tolerance was induced by a pellet implant method. These animals were tolerant to morphine regardless of the route of administration. Peptides arginine vasopressin (AVP) and cyclo (Leu-Gly) (cLG) were tested for their ability to alter tolerance. AVP was found to facilitate the development of ED tolerance but had no effect on EI tolerance. On the other hand cLG blocked the development of EI tolerance without affecting ED tolerance. The determination of brain morphine levels indicated that the ED tolerance produced by this method is dispositional while EI tolerance is functional. PMID- 4022280 TI - Oxytocin stimulates lordosis behavior in female rats. AB - Oxytocin, either intraperitoneally injected (200 ng/rat) or intracerebroventricularly infused (1 ng/rat in 4 microliters saline) 60 and 15 min respectively before testing, significantly increased the lordosis response to the mounting male of ovariectomized, estrogen/progesterone treated rats. The intracerebroventricular infusion of oxytocin 0.1 ng/rat had no effect; nor did saline. These results indicate that oxytocin increases female receptivity, the site of action probably being in the central nervous system. PMID- 4022282 TI - Postoperative extradural hematoma associated with induced hypertension. AB - We describe a patient who developed a delayed postoperative hematoma while receiving hypertensive therapy for delayed cerebral ischemia after aneurysm operation. The association between delayed extradural hematoma and induced hypertension has not been described previously. PMID- 4022283 TI - Surgical considerations in the initial repair of meningomyelocele and the introduction of a technical modification. AB - Tethering of the spinal cord has been increasingly recognized as a cause of late deterioration in the child with repaired meningomyelocele. Findings at reoperation include dense arachnoiditis, dermal inclusion cysts, fibrolipoma of the filum terminale, and, on occasion, foreign body granulomas. This article reviews four key steps in meningomyelocele repair and the guidelines for detection of surgically remediable lesions associated with this disorder. In addition, it proposes a modification of the standard dural closure that may reduce the incidence of contributory adhesive arachnoiditis by the creation of a capacious cerebrospinal fluid space about the neural plaque. PMID- 4022284 TI - Primary intracranial rhabdomyosarcoma. AB - Primary intracranial rhabdomyosarcoma is rare. Twenty-one cases with dismal outcomes have been reported. We add five children with this disease treated between 1977 and 1982. Their therapy consisted of surgical resection, craniospinal irradiation, and intravenous-intrathecal chemotherapy. Two children have recovered, 21 and 67 months after diagnosis; the last is the longest survival reported in the literature. Two succumbed to tumor recurrence, and one died due to pulmonary embolism. The posterior fossa was invariably a site of tumor at presentation. Diagnosis with light microscopy can be elusive; electron microscopic and immunohistochemical evaluation are necessary to confirm the pathological condition. This is essential so that early, aggressive therapy can be instituted. These diagnostic and therapeutic techniques have led to a reevaluation of this malignancy and its prognosis. PMID- 4022285 TI - Severe hypophosphatemia after head injury. AB - Hypophosphatemia occurs in a variety of clinical conditions. It develops in parallel with phosphate depletion from body losses or more commonly as a sequel to the redistribution of phosphate from the extracellular to the intracellular compartment. Hypophosphatemia is a multisystem disturbance capable of involving the neurological, immunological, and muscular systems, among others. In this report, we describe five patients with severe head injury who developed marked hypophosphatemia (less than 1 mg/dl) within 24 hours of hospitalization. This fall in serum phosphate coincided with the induction of respiratory alkalosis consequent to mechanical ventilation. In four of the five patients, as acid-base parameters returned to normal, serum phosphate values rose, in all instances reaching values greater than 2.5 mg/dl. Urinary phosphorus excretion, ordinarily negligible after hypophosphatemia induced by hypocapnia, was still present in Cases 1 and 4 (greater than 600 mg/24 hours). This is unexplained by any of the known hormonal or fluid alterations that accompany head injury. These five patients developed severe, yet transient, hypophosphatemia that resolved upon correction of hyperventilation-induced acid-base abnormalities. We discuss the pathophysiology of this entity and the implications for the head trauma patient. PMID- 4022286 TI - Subtle neuropsychological deficits in patients with good recovery after closed head injury. AB - This study demonstrates residual mental deficits in patients who have apparently recovered after closed head injury. Twenty closed head injury patients were compared to 20 normal control subjects matched for age, sex, handedness, education, language, and IQ. All received a series of neuropsychological tests. Discriminant function analysis significantly differentiated the two groups. Correct classification of individuals as having suffered a head injury or not was 85%. The head injury patients did have primary impairment on tests of divided attention. Litigation was not a factor. We propose that this impairment of information processing reflects residual brain damage secondary to the closed head injury. PMID- 4022287 TI - The "hyperacute" extraaxial intracranial hematoma: computed tomographic findings and clinical significance. AB - Thirteen patients with acute subdural and epidural hematomas were found to have fresh, unclotted blood at the time of surgical decompression several hours after injury. Computed tomographic (CT) scans of these patients demonstrated areas of hyperdensity, corresponding to clotted hematoma, admixed with areas of isodensity, corresponding to liquid blood. Active bleeding from identifiable loci was found in 11 patients, 4 of whom had massive hemorrhages. Clotting abnormalities ranging from slightly elevated laboratory test results to a full blown clinical picture of disseminated intravascular coagulation occurred in 8 patients. We describe the CT pictures of these "hyperacute" lesions, and we postulate that such CT presentations indicate either the presence of ongoing active intracranial bleeding or the onset of a coagulopathy complicating the management of these lesions. PMID- 4022288 TI - Cerebrospinal fluid dynamics and hydrocephalus after experimental subarachnoid hemorrhage. AB - The effects of three sequential injections of cisternal blood on ventricular size, cerebrospinal fluid (CSF) pressure, CSF formation rate, and CSF absorption rate were evaluated in adult rabbits. Autologous blood was injected into the cisterna magna on Days 1, 4, and 8 and ventriculocisternal perfusion was done on Day 15. Control animals received artificial CSF injection at these intervals. For each rabbit, the mean CSF pressure was higher after three injections of blood than before: 13 animals after blood injection had a mean CSF pressure of 15.59 +/ 1.15 cm H2O (mean +/- SE); before blood injection, their pressure had been 11.14 +/- 1.43 cm H2O (all figures are means +/- SE). This is a significant increase in pressure (P less than 0.01, paired t-test). Further, the 13 rabbits with cisternal blood injection had a significantly higher CSF pressure than 5 control animals: 15.59 +/- 1.15 vs. 10.50 +/- 1.06 cm H2O. The animals with cisternal blood injection all developed some degree of hydrocephalus; the ventricle to brain percentage ratio was 9.84 +/- 0.56 in blood-injected animals and 2.38 +/- 0.21 in control animals (P less than 0.01, two-tailed t-test). CSF formation and absorption rates were not significantly different after subarachnoid hemorrhage. The CSF formation rates were 9.85 +/- 1.8 microliter/minute in the experimental group and 9.53 +/- 1.9 microliter/minute in the control group; CSF absorption at the animal's opening pressure was 13.30 +/- 2.06 microliter/minute in the animals with cisternal blood injection and 9.97 +/- 2.4 microliter/minute in the control animals.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4022289 TI - Intraventricular morphine in paraneoplastic painful syndrome of the cervicofacial region: experience in thirty-eight cases. AB - The authors report their personal experience with the administration of microdoses of morphine hydrochloride by the intraventricular route through a subcutaneous reservoir for the treatment of paraneoplastic painful syndrome of the cervicofacial region in 38 patients. The results obtained are very encouraging. PMID- 4022290 TI - Validity of measurements of cerebrospinal fluid outflow resistance estimated by the bolus injection method. AB - Estimation of cerebrospinal fluid (CSF) outflow resistance (Ro) using a bolus injection method was carried out under normal conditions and in a state of artificially increased elastance produced by saline loading into the CSF space. These values of Ro were compared with Ro estimated by the steady state infusion method. Saline loading into the subarachnoid space decreased the buffering capacity significantly, as represented by the pressure-volume index (PVI), which was lowered from 0.72 ml under normal conditions of 0.56 ml during saline loading. The estimated values of Ro under normal conditions and during saline loading were 90.6 and 133.6 mm Hg/ml/minute, respectively. The steady state infusion method yielded an Ro value of 166.3 mm Hg/ml/minute. Ro was therefore considerably underestimated by the bolus method when used under normal conditions of resting intracranial pressure. Moreover, its error was bigger when Ro was higher. On the other hand, during the course of saline loading, the estimated value of Ro using the bolus method was not significantly different from that estimated by the steady state infusion method, even in the higher range of Ro. Estimation of Ro by the bolus injection method was more reliable when the buffering capacity of the craniospinal space was reduced. PMID- 4022291 TI - Cholesterol granuloma of the petrous apex and sphenoidal sinus: a case report. AB - A case of a cholesterol granuloma located in the petrous apex and eroding into the sphenoidal sinus is reported. Cholesterol granuloma is thought to occur when pneumatized cells in the temporal bone become obstructed. Although usually occurring in the middle ear, it can occur in the petrous apex. The diagnosis and surgical management are discussed. PMID- 4022292 TI - Hydromyelia complicating Apert's syndrome: a case report. AB - A 7-year-old boy with Apert's syndrome and hydrocephalus presented with scoliosis and lower extremity weakness. Neuroradiological evaluation demonstrated bony abnormalities involving the foramen magnum and a markedly hydromyelic spinal cord. Clinical improvement followed posterior fossa decompression and a myelotomy on the caudal conus medullaris. A possible role of the craniofacial anomaly in the pathogenesis of the hydromyelia is discussed. PMID- 4022293 TI - Metastatic meningioma to cervical vertebra: case report. PMID- 4022294 TI - Anterointernal approach to the lumbar spine: technical note. AB - Lumbar surgery is currently benefiting from the development of anterior approaches to the spine and the possibilities of anterior arthrodesis. The transperitoneal approach is being replaced more often by an extraperitoneal approach that enables anterior access to the spine. The authors report an anterointernal approach to the lumbar spine. PMID- 4022295 TI - Posttraumatic meningioma. AB - This report concerns three patients with intracranial meningioma developing at the site of an old head injury with skull fracture. These cases, along with literature reports, suggest a causal relationship between head trauma and the subsequent development of meningioma. PMID- 4022296 TI - Multiple intracranial arteriovenous malformations: case report. AB - The authors describe a case of multiple supratentorial intracranial arteriovenous malformations in a patient with a family history of cerebrovascular disease. There was no sign of any other vascular dysplasia. A brief review of this rare entity is given. PMID- 4022297 TI - Use of acrylic in anterior cervical discectomy: technical note. AB - Acrylic was inserted into the intervertebral space after anterior cervical discectomy in five patients. The application of the acrylic was simple and quick to perform and atraumatic to the patient. The intervertebral space was preserved satisfactorily and consistently in all five patients. With this technique, the complications associated with bone grafts can be avoided. PMID- 4022298 TI - Multiple unusual aneurysms and arteriovenous malformation in a single patient: a case report. AB - A patient with multiple unusual aneurysms and an arteriovenous malformation (AVM) is presented. Aneurysms involving the meningohypophyseal trunk and the feeding vessel of the AVM were observed. Two additional aneurysms assumed a pantaloon appearance. The largest aneurysm was responsible for the patient's subarachnoid hemorrhage. This aneurysm and two adjacent aneurysms were clipped successfully, and the patient made an uneventful recovery. Subsequent angiography revealed a stable appearance of the remaining aneurysms and AVM. PMID- 4022299 TI - Parietal hemineglect and motor deficits in the monkey. AB - To study the parietal hemineglect syndrome, we trained and operated nine Macaca fasicularis monkeys. Contralateral to the lesion they showed response abnormalities to visual and somatic sensory stimuli, and misreaching toward targets in visual space, abberant finger and wrist postures and lack of pincer grasp. The latter did not appear during performance of a preoperatively practised task, nor depend for severity upon lesion size, whereas sensory response abnormalities did. We conclude that abnormal motor patterns are separable from hemineglect in parietal animals, and are worst when the movement is directed to a visual target in extrapersonal space. PMID- 4022300 TI - Enhanced dual task performance following corpus commissurotomy in humans. AB - A commissurotomy patient and two neurologically intact control observers were required to encode spatial patterns presented concurrently to the two hemifields. Under conditions of maximal perceptual load, in which different patterns appeared in the two fields, the commissurotomy patient encoded more information than the control observers. Based on these findings, it is concluded that competition for common internal processing mechanisms interferes with overall processing efficiency. PMID- 4022301 TI - Reaction times to lateralized visual stimuli in callosal agenesis: stimulus and response factors. AB - A young acallosal man was intensively tested in a standard simple reaction time (RT) paradigm using briefly-presented lateralized spots for light. In Experiment 1, findings on previous acallosal patients of a large disadvantage for crossed (e.g. right hemifield-left hand) as against uncrossed (e.g. left hemifield-left hand) RTs were replicated. This crossed-uncrossed difference (CUD), as in previous work, turned out to be smaller in a bimanual response task than in the conventional unimanual task. Experiment 2 was a factorial study of unimanual RTs in which (a) stimulus intensity and (b) spatial S-R compatibility, were varied. As in a previously tested patient, decreased intensity resulted in a greatly increased CUD. S-R compatibility on the other hand had no effect on CUD. The results are interpreted as favouring a role for visual commissural neurones in the acallosal CUD, and as evidence against a spatial compatibility hypothesis. PMID- 4022302 TI - Neuropsychological patterns of presenile and senile dementia of the Alzheimer type. AB - Thirty-seven patients with a presumptive diagnosis of dementia of the Alzheimer type were divided into presenile and senile groups according to the age at which they first received a clinical diagnosis. Although there were no differences in mental status, dementia rating, or chronicity of disease, multivariate analyses of WAIS subtests revealed the presenile subjects to be relatively impaired on Performance subtests. Univariate tests of Verbal, Performance, and Full Scale IQ measures were significantly lower in the presenile group. There was no group effect detected for Digits forward, adjusted for age differences based upon performance of 40 age-matched controls, while the presenile group performed significantly more poorly on backward span. Further, significant differences were detected for an embedded figure task, as well as graphomotor speed. These data suggest that patients who develop a degenerative dementia during the presenile period are more impaired than their senile counterparts on age-adjusted measures of sustained concentration and mental tracking. PMID- 4022303 TI - Cognitive risk-taking after frontal or temporal lobectomy--I. The synthesis of fragmented visual information. AB - Patients with unilateral cerebral excisions and control subjects performed two visual tasks in which target items had to be guessed on the basis of partial information. In one task, no points were at stake, but in the second, each cumulatively provided clue was assigned successively lower point-value, these points being risked whenever the subject responded. The right fronto-temporal group chose to guess more often after seeing only one clue than any other group. The right temporal-lobe group and both frontal-lobe groups were impaired at synthesizing the fragmented line-drawings, with patients in the frontal-lobe groups making the most perceptual errors. PMID- 4022304 TI - Cognitive risk-taking after frontal or temporal lobectomy--II. The synthesis of phonemic and semantic information. AB - Patients with unilateral cerebral excisions and control subjects performed two tasks in which target words had to be guessed on the basis of either phonemic or semantic partial-information clues. Each cumulatively provided clue was assigned successively lower point-value, these points being risked whenever the subject responded. Patients with frontal-lobe excisions chose to make a guess after seeing only one clue more often than did a combined group of subjects without frontal-lobe damage, but this guessing-score was also related to extent of right temporal-lobe removal. Patients with left temporal-lobe or left frontal-lobe lesions had difficulty solving the verbal clues, occasionally failing to recognize that a response generated in the context of one clue satisfied all the clues. PMID- 4022305 TI - Information processing deficits in Parkinson's disease during movement. AB - The capacity to process information during movement selection and execution was studied in Parkinsonian patients and controls in a task involving movement of a hand-held stylus between two targets whose size and separation could be systematicaly varied. Movement time and accuracy were evaluated when the size and required accuracy of movements were changed to modify movement difficulty. Movement time and inaccuracy of patients with Parkinson's disease were exaggerated by increasing target separation so as to increase movement extent (target size held constant) or by decreasing target size (target separation held constant). The fact that these changes in task difficulty caused greater deterioration of performance for patients than for controls is consistent with previous studies indicating that Parkinsonian patients have deficits in executing high-velocity movements. These data also show that performance deficits by Parkinsonian patients can be brought out by increasing movement difficulty through requiring increased movement accuracy. These findings are interpreted in relation to the relative contribution of deficits in movement execution vs motor programming in the motor disorders of Parkinson's disease. PMID- 4022306 TI - Classification of reading disability in a case of congenital brain damage. AB - The reading and spelling abilities of an 18-yr-old spastic quadriparetic cerebral palsied female patient are studied in detail. Reading and spelling errors are related to performance on several neuropsychological tests. The patient's reading disability is compared to that found in both developmental and acquired dyslexia. Some similarities are shown to various developmental dyslexia subtypes who are impaired in visual perception or rely upon left hemisphere based reading strategies. She also is somewhat like the acquired dyslexia cases classified as either surface or visual dyslexics. The most salient characteristic of her reading is the degree to which both visual and auditory factors prevent the acquisition of advanced skills. PMID- 4022307 TI - Motor correlates of dichotic listening asymmetries in children. AB - The purpose of this study was to determine the predictive relation between incidence of unintended motor overflow and degree of asymmetry on a dichotic word identification task in children. Seventy-eight third grade girls and 67 fifth grade boys were seen longitudinally over a 2-yr period. Among girls, incidence of overflow, primarily contralateral, accounted for nearly 20% of the variance in dichotic listening scores; but the results were not reliable for boys. The findings support the contention that suppression of the non-dominant hemisphere is an important mechanism underlying dichotic listening performance. PMID- 4022308 TI - An association between hand preference and tactile discrimination performance in the rhesus monkey. AB - Seventy-eight rhesus monkeys spontaneously using the left hand learnt a tactile discrimination task in significantly fewer trials than 77 monkeys using the right hand; but 82 monkeys without consistent preferences learnt significantly faster than either group with consistent preferences. PMID- 4022309 TI - Language dominance: correlation of radiological and functional data. AB - Morphological asymmetry of the posterior sylvian region was measured in carotid arteriograms of patients with medically refractory seizures. Anatomical asymmetry correlated with ear superiority on dichotic listening tests. PMID- 4022310 TI - Bisecting rods and lines: effects of horizontal and vertical posture on left-side underestimation by normal subjects. AB - In Experiment I normal subjects performed the classical clinical line-bisection task, and demonstrated a left-side underestimation. In Experiment II subjects maintained fixation upon a central position and adjusted a rod passing through this fixation point so that both extremities were judged equal. The left-side underestimation was very much greater under these conditions, but was considerably reduced when retinal and gravitational coordinates were dissociated by making the subjects lie horizontally on one or other side. Subjects then demonstrated greater left-side and top-half underestimation when lying on the left than on the right side. Gravitational coordinates and the apparent locus of events in extrapersonal space are determinants of perceptual asymmetries at least as important as anatomical connectivities. PMID- 4022311 TI - S-R compatibility effect or cerebral laterality effect? Comments on a controversy. AB - This article investigates the role played by misleading terminology in the origins of a recent controversy about the nature of stimulus-response compatibility effects. PMID- 4022312 TI - Dissociated hemispheric superiorities for reading stenography vs print. AB - In two lateralized tachistoscopic lexical decision experiments at different exposure durations, we found for high-frequency function words written in stenography a shift from a RVF advantage at long exposures to a LVF advantage at short exposures, while for the same words written in print a strong RVF effect persisted. We suggest that a reduction of exposure duration, together with the strong visuo-spatial features in stenography, activate right-hemispheric word recognition. Stenography, a non-orthographic and syllabic-ideographic writing system, could be a model to investigate different hemispheric reading processes in Western subjects. PMID- 4022313 TI - The sex difference in dichotic listening: multiple negative findings. AB - Verbal dichotic listening tests were administered to 477 normal, right-handed adults in five consecutive experiments. None of the five separate analyses yielded a significant sex difference in degree of ear asymmetry, nor was a significant difference found when data were pooled. Supplemental analyses provided some evidence of a sex difference among subjects without familial sinistrality. Nonetheless, subjects' sex accounts for a very small proportion of the total variance in ear asymmetry. PMID- 4022314 TI - Psychogenic forms of epilepsy. PMID- 4022315 TI - Structural organization indexes of some cortical formations in the left and right hemispheres of the human brain. PMID- 4022316 TI - State of the nonspecific brain systems during cerebral autonomic neurovascular crises and neurogenic syncope. PMID- 4022317 TI - State of intercortical connections after cranial-cerebral trauma with injury to the lower parietal lobe. PMID- 4022319 TI - The speech syndrome and its dynamics in patients after ischemic stroke. PMID- 4022318 TI - Compressed spectral analysis of the EEG in patients with acute cerebrovascular disturbance. PMID- 4022320 TI - Interhemispheric functional relations in patients with chronic alcoholism. PMID- 4022321 TI - Interhemispheric relations in patients with chronic alcoholism. PMID- 4022322 TI - Effect of hyperventilation on depression of the EEG alpha-rhythm induced by an imagined visual sensation. PMID- 4022323 TI - Disturbances of verbal memory in local lesions of the left and right cerebral hemispheres. PMID- 4022324 TI - Calculation disturbances in the clinical picture of local brain lesions. PMID- 4022325 TI - Ultrastructure of nerve tissue on experimental brain injuries in animals with increased immunobiological reactivity of the body on action of some desensitizing preparations. PMID- 4022326 TI - Changes in the time required for a simple motor response of the hand in patients with craniocerebral injuries. PMID- 4022327 TI - Frontal cortex projections to the amygdaloid central nucleus in the rabbit. AB - Evidence has recently been presented which demonstrates that the amygdaloid central nucleus projects directly upon cardiovascular/autonomic regulatory nuclei of the dorsal medulla and that in the rabbit this nucleus may influence cardiovascular activity during emotional states. The present study is one of a series of investigations designed to provide information on the innervation of the central nucleus in the rabbit and describes the topography and origin of frontal cortex projections to the nucleus based upon retrograde and anterograde axonal transport techniques. Injections of horseradish peroxidase or the fluorescent dyes, Bisbenzimide or Nuclear Yellow, into the central nucleus resulted in abundant numbers of retrogradely labeled neurons in three regions of the frontal cortex: the insular cortex on the lateral surface and areas 25 and 32 on the medial surface of the hemisphere. The majority of labeled neurons in the insular cortex were located in layer V of the dorsal and posterior agranular insular regions, although labeled neurons were observed in layer V of the granular insular cortex as well as in layers II and III of the posterior agranular insular cortex. Labeled neurons in areas 25 and 32 were located throughout all layers and the total number of these neurons was substantially less than that observed in the insular cortex. Autoradiographic experiments in which amino acids were injected into the insular cortex resulted in a dense pattern of transported label within the central nucleus that extended rostrally into the sublenticular substantia innominata and lateral component of the bed nucleus of the stria terminalis. Label was also observed in the cortical, lateral, basolateral and basomedial amygdaloid nuclei. In contrast to the projections from the insular cortex, amino acid injections into areas 25 and 32 resulted in only relatively light labeling within the most rostral region of the central nucleus; otherwise the nucleus was partially encapsulated and virtually devoid of label. These results suggest that the insular cortex possesses the potential to directly influence the central nucleus projection to cardiovascular/autonomic regulatory nuclei of the dorsal medulla and thus, together with the amygdaloid central nucleus, appears to be an important component of a forebrain system involved in cardiovascular/autonomic regulation. PMID- 4022328 TI - Vasopressin- and neurophysin-immunoreactive neurons in the septal region, medial amygdala and locus coeruleus in colchicine-treated rats. AB - The distribution and morphology of neurons containing vasopressin, oxytocin and their associated neurophysins were examined immunohistochemically in rats given intracerebroventricular injections of colchicine. Under these conditions, numerous neurons containing vasopressin and neurophysin were found in several brain areas in addition to those previously described in the hypothalamus. Individual parvocellular vasopressin neurons were scattered in the medial and lateral septum and vertical limb of the nucleus of the diagonal band, while a large number of such neurons were found throughout both the bed nucleus of the stria terminals and the dorsal portion of the medial amygdala. In addition a small cluster of parvocellular vasopressin neurons was present adjacent to the top of the third ventricle in the posterior dorsal hypothalamic area and a number of such neurons were found in the ventral locus coeruleus and sub coeruleus. The mean diameters of these parvocellular vasopressin neurons ranged from 16.6 to 19.8 micron in the different regions, in contrast to the 25.4 micron mean diameter of hypothalamic magnocellular vasopressin neurons, or the 13.7 micron mean diameter of parvocellular vasopressin neurons in the suprachiasmatic nucleus. No vasopressin neurons were found in other brain and spinal cord regions under the conditions used in this study, although all regions were examined. No oxytocin neurons other than those previously described in the hypothalamus and immediately contiguous regions were found. Measurement of the mean diameter of oxytocin neurons showed that neurons in the caudal paraventricular nucleus were clearly smaller (18.9 micron) than magnocellular oxytocin neurons (24.8 micron) in other parts of the hypothalamus. These parvocellular oxytocin neurons with experimentally documented central connections were similar in both size and appearance to the parvocellular vasopressin neurons seen after colchicine treatment, which are potential sources of certain central vasopressin pathways. These findings indicate that there are at least two types of oxytocin neurons in the hypothalamus and several types of vasopressin neurons in a variety of different areas in the brain, many of which are outside of the hypothalamus. PMID- 4022329 TI - Cholinergic influences on hippocampal glucose metabolism. AB - 2-Deoxy-D-[3H]glucose autoradiography was employed to investigate the effects of acute cholinergic manipulations on hippocampal glucose metabolism. In general, manipulations designed to reduce cholinergic activity (medial septal ablation, atropine treatment) reduced hippocampal glucose metabolism. Maximal decrements were found in the terminal fields of the septohippocampal projection after medial septal lesions, while maximal deficits after atropine treatment correlated with muscarinic receptor binding. Electrical stimulation of the medial septum resulted in increased glucose utilization in some terminal fields of the septohippocampal projection and decreased utilization in the terminal fields of the perforant pathway. Our data clearly indicate that acute alterations in cholinergic activity can affect hippocampal glucose metabolism but the distribution, direction and degree of these changes is dependent on the specific treatment. PMID- 4022330 TI - Topographic organization of the cerebellothalamic projections in the rat. An autoradiographic study. AB - The topographical organization of the subnuclear projections towards the thalamus was studied with autographic methods in adult Wistar rats. The four cerebellar deep nuclei give rise to projections to the ventral region of the rostral thalamus. Most of the fibers end contralaterally, according to a topographical pattern; however, some fibers from each of the cerebellar nuclei recross the midline at the thalamic level and terminate ipsilaterally, within regions symmetric to those receiving the densest contralateral projection. These ipsilateral cerebellothalamic components arise in decreasing order from the caudal nucleus lateralis, the ventrocaudal nucleus medialis and the nucleus interpositus, respectively. The projections of the nucleus lateralis directed to the contralateral thalamus are topographically organized. (1) Within the nucleus ventralis lateralis, the rostral and caudal parts of the cerebellar nucleus lateralis project respectively to rostral and caudal regions; lateral and medial zones of the nucleus lateralis project, respectively, to medial and central aspects of the nucleus ventralis lateralis. (2) The nucleus ventralis medialis and particularly its caudal portion appears to receive the bulk of its afferents from the ventromedial portion of the nucleus lateralis including the "subnucleus lateralis parvocellularis". (3) The nucleus centralis lateralis receives fibers from most parts of the nucleus lateralis including the "dorsolateral hump". (4) The nucleus interpositus anterior projects to the dorsomedial aspect of the rostral nucleus ventralis lateralis. In the latter nucleus, the ventrolateral aspect of the central region receives projections in cases in which the nucleus interpositus posterior is largely involved. A particular emphasis is put on the different projections from the various subnuclear regions of the lateral nucleus. A comparison is attempted with the situation in the primates, particularly with regard to the question of the parvocellular subdivision of the lateral nucleus. PMID- 4022331 TI - Quantitative analysis of the topographical organization of olivocerebellar projections in the rat. AB - The inferior olivary projection to anterior and posterior regions of the cerebellar vermis was studied in the rat using the retrograde fluorescent double labelling technique in combination with a computerized data collection system. A technique for quantifying and statistically analysing the point-to-point (or nucleotopic) organization of the projection is presented. It was found that one group of neurones in the medial accessory olivary nucleus projected to cerebellar lobules 6 or 7, and second group projected to lobules 4 or 5, while a third sent collaterals to both areas. In the rostral part of the nucleus these three groups were spatially separated (P less than 0.05), whereas caudally they were intermingled. It is concluded that a double-labelling method has distinct advantages over a single-tracer technique (such as horseradish peroxidase) in the investigation of the topographic organization of neuronal projections. Quantitative analysis is used here to overcome the problems presented by collateralization, inter-animal variation and the accurate representation of results from a series of animals. PMID- 4022332 TI - The mormyrid brainstem--II. The medullary electromotor relay nucleus: an ultrastructural horseradish peroxidase study. AB - The medullary relay nucleus of the mormyrid weakly electric fish Gnathonemus petersii is a stage in the command pathway for the electric organ discharge. It receives input from the presumed command or pacemaker nucleus and projects to the electromotoneurons in the spinal cord. Its fine structure and synaptology were investigated by electron microscopy. The origin of the terminals contacting the cell membrane of the neurons of this nucleus was determined by horseradish peroxidase (HRP) injections into different brain structures, namely into the bulbar command- and mesencephalic command-associated nuclei. Twenty-five to thirty large cells of about 45 micron in diameter constitute the medullary electromotor relay. Each cell has a kidney-shaped, lobulated nucleus, a large myelinated axon with a short initial segment and several long, richly arborizing primary dendrites. Many, if not all, cells are interconnected with large somatosomatic or dendrosomatic, dendrodendritic and dendroaxonic gap junctions. These junctions often occur in serial or triadic arrangements. The relay cells receive large club endings as well as small boutons. The club endings are found mainly on the soma and primary dendrites and are morphologically mixed synapses. The boutons are characterized by synapses which are only chemical and are distributed all over the cell membrane, but with a definitely higher frequency on secondary dendrites and more distal parts of dendritic processes. Horseradish peroxidase injections into the mesencephalic command-associated nucleus reveal a large number of labelled boutons on the secondary dendrites of the relay cells. Injections into the bulbar command-associated nucleus label the same type of boutons as mesencephalic injections, but also label club endings on relay cell soma and primary dendrites. The results support the conclusion made on the basis of previous light microscopical observations that boutons originate from the bulbar command-associated nucleus, whereas the club endings issue from the presumed pacemaker nucleus (nucleus c). The club endings of the bifurcating axons of this nucleus are labelled by retro- and anterograde transport of horseradish peroxidase; the bifurcating axons project simultaneously to the bulbar command associated nucleus and the medullary relay nucleus. PMID- 4022333 TI - The mormyrid brainstem--III. Ultrastructure and synaptic organization of the medullary "pacemaker" nucleus. AB - The ultrastructure and synaptic organization of the presumed medullary pacemaker nucleus, nucleus c of the weakly electric mormyrid fish, Gnathonemus petersii has been investigated. Nucleus c consists of about 12-15 small (20-25 micron) neurones (P-cells), which form a group situated ventrally to the medullary relay nucleus and embedded in a neuropil of myelinated fibres and dendritic processes. The P-cells often exhibit an enhanced electron density of their cytoplasm and dendroplasm. They possess several dendrites of different diameter, a short, thin axon initial segment and a thickly myelinated axon running in dorsal direction. The pacemaker neurons are interconnected by complex electronic coupling, established by somatosomatic, dendrosomatic and dendrodendritic gap junctions. Perikarya and dendrites are frequently interconnected serially by gap junctions; dendrites showed sometimes triadic gap-junction arrangement. It is suggested that this high degree of electrotonic coupling amongst the pacemaker cells represents the first level of the highly ordered synchronization processes which characterize the electric discharge command system of Gnathonemus. Pacemaker cells receive synaptic input from club endings with mixed synapses and from bouton-like terminals with chemical synapses, both of them originating from medium-sized myelinated fibres and contacting mainly neuronal perikarya and dendritic processes. The axon initial segment receives only few synaptic inputs. Bouton-like terminals were found to be of two types according to their vesicle content, namely, boutons with ovoid, clear synaptic vesicles forming Gray type-1 synapses and boutons with pleomorphic clear synaptic vesicles forming Gray type-2 synapses. Different functional roles for the two types of boutons in modulating pacemaker cell activity are suggested. PMID- 4022334 TI - Topographic principles in the spinal projections of serotonergic and non serotonergic brainstem neurons in the rat. AB - The spinal projections from the raphe-associated brainstem areas containing serotonergic neurons were studied with aldehyde-induced fluorescence in combination with the retrograde fluorescent tracer True Blue in the rat. This technique makes it possible to determine simultaneously the projections of individual neurons and to detect whether serotonin is present in the same neurons. After tracer injections into the spinal cord retrogradely labeled serotonergic and non-serotonergic neurons were found in the medullary raphe nuclei and adjacent regions and to a lesser extent in association with the dorsal and median raphe nuclei in the mesencephalon. Large True Blue injections that covered one side of the spinal cord at mid-cervical level labeled about 60% of the ipsilaterally situated serotonergic neurons in the medullary raphe regions while the corresponding figure contralaterally was about 25%. On both sides a larger number of labeled non-serotonergic neurons were found; these were sometimes located dorsal to, but often intermingled with, the serotonergic cells. While the serotonergic projection from the mesencephalon could not be labeled from injections below cervical levels, the labeling in more caudal brainstem regions exhibited only minor variations depending on the rostrocaudal level of the spinal segment injected. Furthermore, quantitative data from injections at different levels indicate that the majority of the spinal-projecting neurons traverse most of the length of the cord. Summarizing the results obtained from small injections restricted to subregions of the cord we feel that it is possible to distinguish three fairly distinct pathways for spinal projections from the medullary raphe and adjacent regions: The dorsal pathway originates mainly from cells in the caudal pons and rostral medulla oblongata (rostral part of nucleus raphe magnus, nucleus raphe magnus proper, nucleus reticularis gigantocellularis pars alpha and nucleus paragigantocellularis). This pathway, which contains a large non-serotonergic component, descends through the dorsal part of the lateral funiculus and terminates mainly in the dorsal horn at all spinal cord levels. The intermediate pathway is largely serotonergic with its cell bodies located within the arcuate cell group (situated just ventral and lateral to the pyramids very close to the ventral surface of the brainstem) and in the nucleus raphe obscurus and pallidus and terminates in the intermediate grey at thoracolumbar and upper sacral levels.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 4022335 TI - Effect of facial nerve transection on acetylcholinesterase, choline acetyltransferase and [3H]quinuclidinyl benzilate binding in rat facial nuclei. AB - Choline acetyltransferase activity and localization of acetylcholinesterase and [3H]quinuclidinyl benzilate binding sites (muscarinic receptors) in rat facial nuclei were examined 2 weeks after right facial nerve transection or sham control surgery. Choline acetyltransferase activity in the right facial nucleus of nerve transected rats was only one-third of that in the left nucleus. Histochemical observations revealed loss of acetylcholinesterase from most motoneurons and neuropil of the right facial nucleus after axotomy. Autoradiographic grains, marking muscarinic receptors, were likewise depleted substantially from this region. Facial nuclei of control animals were identical with respect to all of these neurochemical measures and undistinguishable from the left facial nucleus of nerve-transected rats. Cholinergic enzymes are known to be synthesized by motoneurons, but the source of muscarinic receptors in the facial nucleus is not known. Since all three proteins are depleted from the facial nucleus after axotomy of motoneurons, it is concluded that these cells produce cholinergic enzymes and muscarinic receptors. Synthesis of muscarinic receptors by facial motoneurons could indicate these neurons are cholinoceptive. Axotomy should be a useful tool for determining which other neurotransmitter receptors are produced by facial motoneurons and efferent neurons in other cranial nerve nuclei. PMID- 4022336 TI - Physiological properties and pattern of innervation of regenerated muscles in the rat. AB - The regeneration of fast and slow muscles was compared following "mincing" and replacement into their own or alien muscle bed. At intervals varying from 2 to 9 weeks the tension developed by the regenerated muscles was assessed and compared to that developed by the muscles from the contralateral unoperated side. This parameter was then taken as an indication of recovery. The regenerated muscles never developed more than half of the tension of the control muscles. Muscles regenerated in the bed of extensor digitorum longus became fast-twitch muscles and muscles regenerated in the bed of soleus became slow-twitch muscles, no matter whether they originated from an extensor digitorum longus or soleus "mince". The regeneration of the muscle tissue in the place of extensor digitorum longus developed better than in the place of soleus. The pattern of innervation of the regenerated muscles was analysed using a combined cholinesterase silver stain. Many of the regenerated fibres had more than one end plate and some end plates more than one axon terminal. These results show that in adult animals muscle redevelopment can occur, but only to a limited extent. Moreover, on reinnervation of regenerated muscle fibres the axons do not assume their original pattern of innervation. PMID- 4022337 TI - The fate of proliferating cells in skeletal muscle after denervation or tenotomy: an autoradiographic study. AB - During the first 7 days after denervation or tenotomy of skeletal muscle there is increased cell proliferation, as measured autoradiographically by [3H]thymidine incorporation. By 21 days most of the labelled cells have disappeared. The present experiment was designed to measure residual levels of labelling in skeletal muscles at 21 days after denervation or tenotomy, when [3H]thymidine had been available for the first 7 days. This was to determine the fate of cells labelled at 7 days and to detect whether continued cell proliferation had occurred during the intervening period, as evidenced by the dilution of nuclear label. Tibialis anterior muscles of 16 mice were denervated, tenotomized or sham operated, and the animals injected with a single daily pulse of [3H]thymidine for the first 7 days only. In denervated muscle the 11% of muscle nuclei and 41% of connective tissue nuclei labelled at 7 days had decreased to 2 and 13%, respectively, by 21 days. These values were still significantly higher than in 21 day controls (0.2 and 1.9%, respectively). In muscle nuclei (myonuclei and satellite cell nuclei) there was a significant decrease in the amount of label per nucleus. This was interpreted as evidence of continued cell proliferation. However, this did not produce an increase in numbers of muscle nuclei. It was concluded that: there was turnover of satellite cells and possibly myonuclei, the latter probably through continued division and incorporation of satellite cells; and the extra satellite cells and myonuclei produced were probably extruded from the fibre to the extracellular space.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4022338 TI - Regrowth of cholinergic and catecholaminergic neurons along a peripheral and central nervous pathway. AB - The transitional region between the peripheral and central nervous system in lumbosacral dorsal roots of rats were used in order to test the regeneration capacity of neurons with different metabolic characteristics. Ventral root fibres (cholinergic) and hypogastric nerve fibres (catecholaminergic) were coapted to the central stump of cut lumbosacral dorsal roots and permitted to regrow along the peripheral nervous and central nervous parts of the dorsal root. After a postoperative period of 1.5-9 months the animals were sacrificed and the coapted nerves and roots were investigated by histochemistry, light and electron microscopy. Regrowth of both cholinergic and catecholaminergic neurons had occurred into the peripheral nervous part of the root. In the central nervous part of the root, regeneration was abortive for both types of neurons. The astrocytes of the central nervous part of the root showed different morphological features according to the type of neuron that had been coapted to the dorsal root. The results are discussed in terms of neurotropism, neuron target dependence, microenvironment and type of regenerating neuron. PMID- 4022339 TI - Autoregulation of histamine release in brain by presynaptic H3-receptors. AB - Regulation of histamine release was studied mainly on brain slices prelabeled with L-[3H]-histidine and depolarized by increased extracellular K+ concentration or veratridine in a non-superfused system. The released 3H-labeled amines, isolated by ion-exchange chromatography from a large excess of 3H-labeled precursor consisted by more than 95% of unchanged [3H]histamine. Exogenous histamine reduced the release of neosynthesized [3H]histamine via stimulation of previously characterized H3-receptors whereas it did not modify the 3H-labeled amine release from slices prelabeled with preformed [3H]histamine. The maximal inhibitory effect of exogenous histamine progressively diminished as the strength of the depolarizing stimulus or the external Ca2+ concentration were elevated. On the contrary H3-receptor antagonists like impromidine or burimamide enhanced the depolarization-induced release of [3H]histamine, an effect which was particularly marked when slices were loaded with histamine by preincubation with [3H]histidine in high concentration. These results suggest that the inhibition of [3H]histamine release by exogenous histamine acting via H3-receptor stimulation is mediated by a restricted access of Ca2+ and that its extent is influenced by the degree of autostimulation by endogenous histamine as well as, possibly, by actual internal Ca2+ concentration. In addition the decrease in external Ca2+ concentration shifted rightwards the concentration-response curve to histamine. The autoinhibitory effect of exogenous histamine was found on slices from various regions, known from lesion studies to contain terminals of extrinsic histaminergic neurons. It did not apparently involve interneurones, not being prevented in slices in which the traffic of action potentials was blocked by tetrodotoxin. It also remained unaffected in striatal slices in which the neuronal cell-bodies were selectively destroyed by prior local infusion of kainic acid. Finally exogenous histamine inhibited [3H]histamine release from depolarized synaptosomes of rat cerebral cortex, with an EC50 value similar to that found with slices and was antagonised by impromidine with an apparent Ki value similar to that displayed at H3-receptors. It is concluded that histamine modulates its own release from cerebral neurones by interacting with H3 presynaptic autoreceptors and via mechanisms similar to those previously evidenced on other aminergic systems. PMID- 4022340 TI - Membrane-bound choline acetyltransferase in Torpedo electric organ: a marker for synaptosomal plasma membranes? AB - The enzyme choline-O-acetyltransferase catalyses the biosynthesis of acetylcholine from acetyl coenzyme A and choline and is considered as one of the best markers for cholinergic nerve endings. The distribution of this enzymatic activity was analysed during the purification of plasma membranes of purely cholinergic nerve endings isolated from the electric organ of the fish Torpedo marmorata. This tissue, which receives a profuse and purely cholinergic innervation, can be considered as being a "giant" neuromuscular synapse. The isolated nerve endings (synaptosomes) were first osmotically disrupted and their plasma membranes isolated by equilibrium density centrifugation (discontinuous followed by continuous sucrose gradients). Choline acetyltransferase activity was found to exist in three forms: (1) a soluble form (the major one) present in the cytoplasm of the nerve endings, (2) a form which is ionically associated with membranes and which can be solubilized by washing exhaustively the membrane fraction with solutions of high ionic strength (0.5 M NaCl) and (iii) a form which is non-ionically bound to membranes and cannot be solubilized with high salt solution. The soluble and the non-ionically bound activities exhibited very similar affinities for choline (1.34 and 1.64 mM, respectively). The non ionically membrane-associated form of choline acetyltransferase was found to "copurify" with the cholinergic synaptosomal plasma membranes of Torpedo, its specific activity being increased from 122 (crude fraction) to 475 (purified membrane fraction) nmol/h/mg protein. An enrichment was also observed for another cholinergic marker, the enzyme acetylcholinesterase, but not for the nicotinic receptor to acetylcholine, a marker for postsynaptic membranes. No choline acetyltransferase activity could be detected in preparations of synaptic vesicles that were highly purified from the electric organ. Also, the non-ionically associated form of choline acetyltransferase activity was hardly detectable (2.4 nmol/h/mg protein) in fractions enriched in axonal membranes prepared from the cholinergic electric nerves innervating the electric organ. The partition into soluble and membrane-bound activity was also analysed for choline acetyltransferase present in human placenta, a rich source for the enzyme but a non-innervated tissue. In this case the great majority of the enzyme appeared as soluble activity. Very low levels of non-ionically membrane-bound activity were found to be present in a crude membrane fraction from human placenta (2.8 nmol/h/mg protein).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 4022341 TI - Neuronal pathology in the nucleus basalis and associated cell groups in senile dementia of the Alzheimer's type: possible role in cell loss. AB - The loss of cortical cholinergic innervation in senile dementia of the Alzheimer's type (SDAT) is associated with cell loss in the nucleus basalis and related cell groups (magnocellular basal nucleus, MBN). We examined MBN in Nissl , acetylcholinesterase- and thioflavin S-stained sections in two cases of SDAT and in four control brains. Using these sensitive methods, senile plaques were easily demonstrated in MBN, and most MBN neurons showed neurofibrillary degeneration as an early change. Cell loss appeared to be due to maturation of neurofibrillary tangles, displacing normal cellular contents. In contrast to theories that the cell loss in MBN represents retrograde degeneration due to axonal injury in the cerebral cortex, MBN neuronal perikarya may be involved by the same primary processes as cortical neurons. PMID- 4022342 TI - Plasmapheresis and acute Guillain-Barre syndrome. The Guillain-Barre syndrome Study Group. AB - We compared plasmapheresis with conventional therapy in 245 patients with the Guillain-Barre syndrome of recent onset. Statistically significant differences, favoring the plasmapheresis group, were found in terms of improvement at 4 weeks, time to improve one clinical grade, time to independent walking, and outcome at 6 months. Plasmapheresis was not effective for all patients, but was particularly effective for patients who received this treatment within 7 days of onset and for patients who required mechanical ventilation after entry into the study. Plasmapheresis appears to be of benefit in patients with Guillain-Barre syndrome of recent onset. PMID- 4022343 TI - Plasmapheresis in Guillain-Barre syndrome. PMID- 4022344 TI - Preservation of voluntary saccades after intracarotid injection of barbiturate. AB - We studied voluntary saccades in 44 patients undergoing Wada testing before surgery for intractable epilepsy. After intracarotid injection of barbiturate, and while they were hemiplegic, patients could still make voluntary saccades toward or away from the side of injection. Sustained ipsiversive deviation of gaze was not noted. Saccades made away from the side of injection were slower than ipsilateral saccades in only 3 of 10 tests. These data support the hypothesis of parallel, independent pathways from the frontal eye fields and from the superior colliculi to the brainstem reticular nuclei that generate saccades. PMID- 4022345 TI - A microangiopathic syndrome of encephalopathy, hearing loss, and retinal arteriolar occlusions. AB - A syndrome consisting of a subacute encephalopathy, sensorineural hearing loss, and retinal arteriolar occlusions is described in two women. Laboratory investigations did not reveal any systemic vasculitis. CT and cerebral angiography showed no abnormalities, but magnetic resonance imaging revealed small, discrete lesions in the white matter. Biopsy of cortical brain from one patient showed disseminated microinfarcts in the gray matter as well as sclerosis of small vessels. This syndrome is characterized as an occlusive vasculopathy rather than vasculitis, and should be considered in evaluations of young women presenting with encephalopathy and hearing loss. PMID- 4022346 TI - Auditory evoked potentials in coma after closed head injury: a clinical neurophysiologic coma scale for predicting outcome. AB - We studied auditory evoked potentials in 45 head-injured patients. All but three were comatose or stuporous at the time of study. Preservation of brainstem auditory or long-latency auditory evoked potentials predicted good outcome. The Glasgow coma scale (GCS), the clinical subtotal of the neurophysiologic coma scale (NPCS), and the NPCS had predictive accuracies of 71%, 82%, and 82%. Although there were 22 falsely pessimistic predictions with the GCS and 9% with the clinical subtotal of the NPCS, there were no falsely pessimistic predictions with the NPCS. PMID- 4022347 TI - Cerebral blood flow and cognitive impairment in Parkinson's disease. AB - In Parkinson's disease, there is high prevalence of dementia, reduction of the regional cerebral blood flow (rCBF), and neuronal loss and Alzheimer-like pathologic changes in cerebral cortex. Since rCBF is also decreased in Alzheimer's dementia, it is theoretically possible that both decreases in rCBF and cognitive impairment in parkinsonians are caused by a similar mechanism, eg, reduced metabolic demand or loss of cholinergic neurons innervating cortex and microvessels. We therefore measured rCBF using the 133Xenon inhalation technique and evaluated cognitive function with a detailed neuropsychological test battery in 48 patients with Parkinson's disease. Mean brain, hemispheric, and regional flows were decreased in parkinsonians as compared with those in age-matched controls. Most of the cognitive functions were impaired in patients as compared with those in normal subjects. However, there was no correlation between the magnitude of rCBF reduction and the presence and severity of intellectual deterioration in parkinsonians, suggesting that each may be caused by a different mechanism. PMID- 4022348 TI - Encephalomyeloneuritis simulating Guillain-Barre syndrome. AB - A patient with encephalomyeloneuritis (EMN) had clinical and laboratory features consistent with severe acute inflammatory polyneuropathy (Guillain-Barre syndrome). CNS involvement was suggested clinically only by transient downbeat nystagmus and by contraction of tensor fascia lata on plantar stimulation. Postmortem examination revealed pathologic changes typical of EMN without systemic neoplasm. Clinical manifestations of the profound central pathology were largely obscured by severe radiculoneuropathy. Pathologic verification of clinically diagnosed inflammatory polyneuropathy is unusual, and CNS disease, therefore, may be more frequent than appreciated, especially in clinical "variants." PMID- 4022349 TI - Reversible chronic cerebellar ataxia after phenytoin intoxication: possible role of cerebellum in cognitive thought. AB - Reversible chronic cerebellar ataxia followed phenytoin treatment in two epileptic women. Cerebellar ataxia in both patients and axonal polyneuropathy in one patient were improved after administration of thiamine alone or with folate. In one patient, some specific behavioral functions improved. However, recovery could have been spontaneous. PMID- 4022350 TI - Combined azathioprine and prednisone in chronic inflammatory-demyelinating polyneuropathy. AB - Twenty-seven patients with static or worsening chronic inflammatory-demyelinating polyradiculoneuropathy were randomly assigned to alternate day decremental prednisone therapy alone or with azathioprine (2 mg/kg) for 9 months. No statistically significant alterations were demonstrated between these treatment schedules. PMID- 4022351 TI - Gelastic seizures, precocious puberty, and hypothalamic hamartoma. AB - The concurrence of gelastic (laughing) seizures and precocious puberty has been reported in 18 patients, including 2 described here. At least 10 patients had hypothalamic hamartomas. Improvements in cerebral imaging permit noninvasive diagnosis. Surgical intervention in seven of these patients was of little diagnostic or therapeutic benefit. PMID- 4022352 TI - Epileptic amnesic attacks: benefit from antiepileptic drugs. AB - We studied two sexagenarians who had recurrent circumscribed attacks of amnesia. Their EEGs showed frequent bilateral spikes that arose independently from the temporal lobes, primarily from mesiobasal structures. Amnesic attacks ceased after treatment with antiepileptic drugs. Neuropsychological tests demonstrated selective cognitive impairments, and short-term memory improved after treatment in one patient. Epileptic amnesic attacks should be distinguished from transient global amnesia, which is clinically similar. PMID- 4022353 TI - Cerebrospinal fluid rhinorrhea during treatment with bromocriptine for prolactinoma. AB - A 47-year-old man exhibited loss of libido and impotence in association with plasma hyperprolactinemia and a pituitary mass with downward extension of the tumor to the sphenoid sinus and to the suprasellar cisterns. Bromocriptine, 15 mg daily, reduced the hyperprolactinemia as well as tumor size. After 8 months on this therapy, the patient developed overt CSF liquorrhea. Five days after discontinuation of bromocriptine, the CSF rhinorrhea stopped, and when bromocriptine was given again 2 weeks later, CSF rhinorrhea returned within 3 days. We believe this phenomenon to be due to retraction of tumor by bromocriptine exposing a defect in the sella floor. Transient occurrence of CSF rhinorrhea can be considered as a consequence of tumor regression in patients on bromocriptine. The possibility of this complication, especially in patients with downward extension of tumor, should be noted. PMID- 4022354 TI - Combined bromocriptine-levodopa therapy early in Parkinson's disease. AB - Compared with levodopa, treatment of parkinsonism for 3 years with bromocriptine alone resulted in less fluctuation and peak-dose dyskinesia, but also less improvement in parkinsonian disability. Only a few of the 76 patients had long term benefit on chronic bromocriptine therapy. However, combined bromocriptine and levodopa therapy had a therapeutic response equal to that of levodopa alone, with fewer fluctuations and peak-dose dyskinesias. Treatment should begin with a low dose of levodopa and a dopamine agonist. PMID- 4022355 TI - Celiac disease and spinocerebellar degeneration with normal vitamin E status. AB - We studied a 47-year-old man with spinocerebellar degeneration and malabsorption due to celiac enteropathy; the serum vitamin E level was normal. The neurologic disorder initially deteriorated despite improvement of small bowel histology on a gluten-free diet and vitamin E therapy, but later stabilized. The etiology of the neurologic disorder in adult celiac disease has not been identified and does not appear to be vitamin E deficiency. PMID- 4022356 TI - Arteriography of the carotid bifurcation: oblique projections. AB - Atherosclerotic plaques may not be demonstrated adequately by standard anteroposterior (AP)-lateral projections of carotid arteriography. We evaluated selective carotid arteriography in oblique projections for 60 individual carotid arteries. Two neuroradiologists evaluated arteriograms in four separate sessions devoted to AP-lateral views alone and in combination with oblique projections. The lumen surface was characterized as "smooth," "irregular," or "ulcerated." When oblique projections were added to AP-lateral views, there was a significant shift of radiologic diagnosis from smooth to irregular or ulcerated. Addition of oblique projections to standard AP-lateral views increases the radiographic diagnosis of carotid artery lesions that may be the source of emboli. PMID- 4022357 TI - Potentially fatal cardiac dysrhythmia and hyperkalemic periodic paralysis. AB - An 11-year-old boy was evaluated for mild periodic muscular weakness exacerbated on separate occasions by disopyramide phosphate and procainamide. He and his mother both had bidirectional ventricular tachydysrhythmia (BVT), short stature, microcephaly, and clinodactyly. The mother, but not the child, had lingual myotonia. The two antiarrhythmic drugs worsened the muscular weakness without benefiting the cardiac dysrhythmia. Potassium loading produced skeletal muscle weakness and transient conversion of the BVT to normal sinus rhythm. Hypokalemia aggravated the BVT without causing weakness. Acetazolamide had no effect. The patient suffered a nonfatal cardiac arrest after several days of increased carbohydrate intake. Imipramine controlled the dysrhythmia without inducing weakness. Periodic paralysis should be considered as the diagnosis in children with BVT, a potentially fatal condition. PMID- 4022358 TI - Syndrome of palatal myoclonus and progressive ataxia: two cases with magnetic resonance imaging. AB - Two patients are reported with palatal myoclonus, progressive ataxia, and dysarthria, unresponsive to treatment with trihexyphenidyl or L-5 hydroxytryptophan. MRI showed enlargement of the inferior olives in one patient, consistent with the pathology usually associated with palatal myoclonus. The syndrome of progressive ataxia and palatal myoclonus should be distinguished from other ataxias and degenerations that affect the brainstem and cerebellum. Pathology and specificity of site of the lesions are distinctive. PMID- 4022359 TI - Parkinson's disease: loss of neurons from the ventral tegmental area contralateral to therapeutic surgical lesions. AB - Decreased numbers of pigmented neurons of the dopaminergic nigrostriatal system are the most striking pathology in the brains of individuals with Parkinson's disease (PD), but it is clear that neurons in the locus ceruleus, vagal nuclei, and nucleus basalis of Meynert are also affected in this disease. Because neurochemical evidence suggested that the mesolimbic dopaminergic system originating in the ventral tegmental area (VTA) may also be involved, the present study was designed to evaluate the mesolimbic dopamine system in PD by counting pigmented neurons in the VTA contralateral to therapeutic lesions placed in the basal ganglia or thalamus. In PD, VTA neurons were depleted to 36 to 55% of control values. Moreover, the VTA showed excessive free pigment, a marker for death of pigmented neurons. These changes may be important in disorders of movement or mentation occurring in PD. PMID- 4022360 TI - Myasthenic crisis after intravenous administration of iodinated contrast agent. AB - Two women with myasthenia gravis became apneic immediately after IV injection of iodinated contrast material for CT. Aggravation of myasthenia continued for days after this initial reaction. PMID- 4022361 TI - Tuberous sclerosis with cardiogenic cerebral embolism: magnetic resonance imaging. AB - A girl with tuberous sclerosis and intracardiac masses had at least two episodes of cardiogenic cerebral embolization, the attacks characterized by acute onset of prolonged neurologic dysfunction arising from different vascular distributions in both cerebral hemispheres. Renal embolization was suggested by hematuria. Magnetic resonance imaging (MRI) demonstrated ischemic lesions in cerebral locations predicted by the clinical signs. MRI also demonstrated extensive areas compatible with the dysmyelination of tuberous sclerosis. PMID- 4022362 TI - Emery-Dreifuss muscular dystrophy with autosomal dominant transmission. AB - A woman with early-onset, slowly progressive, humeroperoneal muscle weakness had marked restriction of neck flexion with contracture at the elbows. She developed exertional dyspnea at age 25, atrial fibrillation with slow ventricular rate was discovered, and a cardiac pacemaker was implanted. Her father had a similar disorder. There is at least one other report of autosomal dominant transmission of this clinical picture, which had previously only been reported as Emery Dreifuss muscular dystrophy with X-linked recessive inheritance. Thus, more than one mode of inheritance is possible for this unusual and distinctive form of muscular dystrophy. PMID- 4022363 TI - Familial spastic paraparesis: an adrenoleukodystrophy phenotype? AB - Adrenoleukodystrophy (ALD) must be considered in the diagnosis of men with progressive nervous system disease. We found the biochemical defect characteristic of ALD in two brothers with spastic paraparesis of late adult onset. Family study then revealed other affected men and asymptomatic heterozygotes in a pattern that conformed to an X-linked pattern of inheritance. PMID- 4022364 TI - Hepatic and encephalopathic components of Reye's syndrome: factor analysis of admission data from 209 patients. AB - Factor analysis of admission data from 209 Reye's syndrome patients yielded three factors. Factor 1 was associated with encephalopathy, blood ammonia, creatinine kinase (CK), uric acid and, to a lesser extent, bilirubin. This factor was linked to the encephalopathy and hypermetabolic changes in muscle, possibly prostaglandin-mediated proteolysis. Factor 2 was associated with serum alanine aminotransferase (AlaAT) and aspartate aminotransferase (AspAT), and was identified as a hepatic lesion component. These factors correspond to two etiologic components of Reye's syndrome. Salicylate was only weakly associated with neuropathic and hypercatabolic indicators and not at all associated with the hepatic damage indicators. PMID- 4022365 TI - Pilot study of fluzinamide (N-methyl-3-[3-(trifluoromethyl)phenoxy]-1 azetidinecarboxamide) in refractory partial seizures. AB - We conducted a pilot study of fluzinamide in 15 adults with refractory partial seizures. After a baseline period, fluzinamide was added to the existing regimen of phenytoin and carbamazepine and increased to maximum tolerated dose. Common side effects included dizziness, diplopia, ataxia, headache, nausea, and rash, resulting in patient withdrawal in six cases. Seizures became less frequent in four of the nine patients who completed the 8-week trial. PMID- 4022366 TI - Locked-in state induced by internal capsule or globus pallidus lesions? PMID- 4022367 TI - Peripheral carbidopa affects striatal monoamine oxidase activity. PMID- 4022368 TI - Whiplash amnesia. PMID- 4022369 TI - Subnormal body temperatures in spinal cord injury. PMID- 4022370 TI - Spontaneous respiratory movements with clinical brain death. PMID- 4022371 TI - More on plasmapheresis in chronic progressive MS. PMID- 4022372 TI - Plexopathy induced by radiation therapy. PMID- 4022373 TI - Usefulness of computed tomography in predicting outcome after aneurysmal subarachnoid hemorrhage: a preliminary report of the Cooperative Aneurysm Study. AB - We evaluated the ability of CT performed soon after subarachnoid hemorrhage (SAH) to predict outcome. Generally, the results of CT paralleled level of consciousness in predicting mortality or good recovery. However, CT did detect some groups of patients who were at greater or lesser risk of mortality. If an alert patient had normal CT, 6-month mortality was 2.8%; if blood was detected, mortality rose to 12.3%. Intracerebral hemorrhage or local, thick, or diffuse subarachnoid deposits of blood seen on CT among alert patients were particularly related to increased mortality. CT abnormalities could be used to detect higher mortality rates among drowsy or comatose patients. CT is useful as an adjunct to the clinical examination in predicting outcome after SAH. PMID- 4022374 TI - The risk of seizure disorders among relatives of children with febrile convulsions. AB - We studied the risk for seizure disorders among relatives of probands with febrile convulsions. The risk for febrile convulsions was raised in siblings, offspring, and nieces and nephews of probands. Risks to siblings were higher if one or both parents also had febrile convulsions, or the proband had no identified neurologic abnormality before the febrile convulsion, if the proband had recurrent febrile convulsions, or the febrile convulsions were complex. The risk for epilepsy was raised in siblings of probands, but not in other relatives. If the proband had febrile convulsions followed by epilepsy, risk to siblings for febrile convulsions and for epilepsy was significantly higher than when probands had either condition alone. PMID- 4022375 TI - The metabolic consequences of experimental intraventricular hemorrhage. AB - Experimental intraventricular hemorrhage was produced by injection of autologous fresh blood (0.25 ml/kg) or artificial CSF into the right lateral ventricle of 24 dogs. A transient ventricular fluid acidosis (pH drop to 7.09) was accompanied by increased lactate, pyruvate, ammonia, and Pco2, and decreased bicarbonate and glucose. High lactate/pyruvate ratios were the most persistent abnormality. The control group, which received intraventricular artificial CSF, developed minimal ventricular fluid acidosis (pH 7.26). Lumbar CSF and venous blood acid-base parameters did not change. Simultaneous cisternal samples obtained from some of the animals reflected similar metabolic abnormalities of lesser magnitude. Intraventricular injection of sodium bicarbonate normalized the pH in four animals. PMID- 4022376 TI - Successful migraine prophylaxis with naproxen sodium. AB - Naproxen sodium, a potent inhibitor of prostaglandin biosynthesis and platelet aggregation, was studied for efficacy in migraine prophylaxis in a randomized, double-blind, placebo-controlled, crossover trial. On naproxen treatment, 52% of the patients had no severe headaches, whereas 19% had no severe headaches during placebo. Naproxen sodium was much better than placebo when patients' diaries were reviewed for severity of attacks, nausea, vomiting, activity reduction, duration of headache, and decreased use of therapeutic medication. The degree of platelet inhibition did not correlate with efficacy in preventing headache. Naproxen sodium can be recommended as a drug of first choice for migraine prevention. PMID- 4022377 TI - Opiate antagonist WIN44,441-3 stereospecifically improves neurologic recovery after ischemic spinal injury. AB - In the unanesthetized rabbit, temporary aortic occlusion results in predictable patterns of spinal cord injury. We use this "spinal stroke" model to assess the potential role of opiate antagonists in treating CNS ischemia. WIN44,441-3 (WIN( ], an opiate antagonist with enhanced activity at the kappa-receptor, reduced motor dysfunction after ischemic spinal cord injury. The effect was stereospecific and dose-related; beneficial actions were seen at doses as low as 40 micrograms/kg. Opiate receptor antagonists may be therapeutically useful in ischemic CNS injury, and the beneficial actions of these compounds may be at the kappa-receptor site. PMID- 4022378 TI - A new method of measuring brain atrophy: the effect of aging in its application for diagnosing dementia. AB - A new method of measuring cerebral atrophy using a ratio of brain parenchyma to ventricular and subarachnoid space is described. It uses digitized brain CT. This ratio was measured prospectively on 117 consecutive elderly patients referred for evaluation of cognitive dysfunction. Diagnosis was determined by preestablished criteria and confirmed by follow-up. Despite the improved accuracy and reproducibility of this method, its ability to differentiate persons with senile dementia of the Alzheimer's type (SDAT) from those suffering from pseudodementia was confounded by age, and was hence of limited utility. We conclude that even with sophisticated measures of cerebral atrophy, CT is unable to discriminate among common causes of cognitive dysfunction in the elderly. PMID- 4022380 TI - Cerebral organization of affect suggested by temporal lobe seizures. AB - A right-handed woman with independent left- and right-sided temporal lobe discharges was studied by continuous EEG and videotape monitoring for 3 weeks. Changes in affect were noted in the immediate and extended postictal periods and varied with the side of discharge. After a left-sided discharge, she became globally aphasic and depressed. Right-sided discharges evoked laughing and postictal hypomania. These manifestations were attributed to contralateral hemispheric disinhibition after ipsilateral seizure inactivation. This case provides evidence that the speech-dominant hemisphere subserves positive feelings and the nondominant hemisphere negative ones. PMID- 4022379 TI - Axonal neuropathy in a patient with IgM M-protein reactive with nerve endoneurium. AB - IgM M-proteins have been found in patients with axonal neuropathies, but it is not known whether these M-proteins bind to nerve components or actually cause the neuropathy. In one patient with axonal neuropathy studied, the IgM M-protein bound to chondroitin sulfate, and there were deposits of IgM in the endoneurium of the patient's nerve. A monoclonal anti-idiotype antibody generated against that M-protein was used to study the binding of the M-protein to normal nerve and to distinguish it from binding of other IgM species that might be present in the patient's serum. In immunofluorescence studies, the M-protein bound to the endoneurium in normal nerve and to connective tissue in other organs. In immunoblot studies, the M-protein bound to several protein bands in nerve and other tissues. The data suggest that the M-protein bound to mucopolysaccharides in nerve endoneurium and connective tissue. PMID- 4022381 TI - Reye's syndrome: incidence and time trends in Olmsted County, MN, 1950-1981. AB - Incidence and time trends of Reye's syndrome have been determined in Olmsted County, MN, using the facilities of the Rochester Epidemiology Program Project at Mayo Clinic. Incidence rates in individuals under 18 years of age were 1.1 per 100,000 person-years in the 1970-75 time interval and 1.7 in the 1976-81 interval. Failure to identify any case in the earliest time interval yields a rate of zero, and an incidence higher than 0.6 per 100,000 can be excluded with 95% probability. This finding is consistent with an increasing incidence over time in this community and does not exclude the possibility that Reye's syndrome did not exist in Olmsted County before 1970. PMID- 4022382 TI - Cessation of stuttering with progressive multiple sclerosis. AB - Two patients stuttered severely into adult years. Stuttering ceased as signs of progressive MS developed. Both patients had clinical evidence of bilateral cerebellar dysfunction, and other forms of speech impairment appeared as the stuttering abated. The cerebellar lesions may have been responsible for the abolition of stuttering. PMID- 4022383 TI - Acquired stuttering from a right hemisphere lesion in a right-hander. AB - Acquired stuttering in adults may follow bilateral or left hemisphere damage, is more common in men than in women, and is often associated with aphasia. After a right hemisphere infarct, a right-handed woman stuttered without aphasia. She had never stuttered previously, but her father and brother both had developmental stuttering. Her case and others suggest that sexual differences in language lateralization may render men more likely to stutter than women after left hemisphere lesions, whereas women are more likely to stutter than men after right hemisphere lesions. PMID- 4022384 TI - Interhemispheric commissurotomy for congenital hemiplegics with intractable epilepsy. AB - Five patients with congenital hemiplegia and intractable epilepsy had interhemispheric commissurotomy (the split-brain operation). After intervals of 2 to 12 years, the response has been excellent in four cases. One patient had moderate benefit. There were no late complications. Commissurotomy seems to be substantially better than hemispherectomy for this syndrome. PMID- 4022385 TI - Familial paroxysmal hypnogenic dystonia. AB - We studied a family with dystonic spasms that occurred with non-REM sleep. This familial disorder may be related to the sporadic cases reported previously. PMID- 4022386 TI - Slow myosin heavy chain isozyme in nemaline myopathy. AB - Muscle biopsies from two sporadic cases of congenital nemaline myopathy were examined for myosin heavy chain composition. Electrophoresis of congenital nemaline myopathy (CNM) muscle myosin in SDS-5% polyacrylamide gels gave rise to a single heavy chain band, with a migration rate and antigenic properties identical to that of the adult slow form, as demonstrated by Western blot techniques and by using specific antibody. Immunofluorescent studies indicate that CNM muscle fibers, including the most severely atrophic fibers, are homogeneous with respect to myosin heavy chain composition. PMID- 4022387 TI - Structural proteins of the opaque muscle fibers in Duchenne muscular dystrophy. AB - We studied the structural proteins of the "opaque fibers" (OFs) in muscle biopsies from 12 patients, aged 4 to 24 years, with Duchenne muscular dystrophy. The electrophoretic patterns of myofibrillar proteins indicated three groups of opaque fibers: the first (OF a) had an almost normal electrophoretogram, the second (OF b1) showed a clear decrease of 55,000 dalton protein (desmin), and the third (OF b2) exhibited a great reduction in alpha-actinin and desmin. The data suggest that some OFs are pathologic fibers in the degenerative process of Duchenne dystrophy. PMID- 4022388 TI - Stretch reflex blepharospasm. AB - We studied a patient with blepharospasm provoked by stretching the orbicularis oculi muscles. With the eyes closed, EMG of the orbicularis oculi at rest revealed spontaneous rhythmic muscle activity that was not visible. When she tried to open her eyes, repetitive jerking blepharoclonus and tonic blepharospasm rendered her functionally blind. Passive stretching of the orbicularis oculi evoked a burst of EMG activity with two components. Touch or pinprick did not elicit such reflex activity. Anesthesia of the supraorbital nerves abolished muscle responses to stretch and improved the blepharospasm. PMID- 4022389 TI - Hyperlipidemic dementia. AB - The dementia of a patient with hyperlipidemia improved dramatically on treatment with diet and fenofibrate. Rheologic study showed an abnormality of rouleaux disaggregation, and this disappeared as plasma lipid levels fell and mental state improved. PMID- 4022390 TI - Primary writing tremor and myoclonic writer's cramp. AB - Four patients with primary writing tremor had a focal, task-specific tremor that responded to anticholinergic drugs. Physiologic features included EMG activity alternating in antagonist muscles, 5- to 20-microV cerebral potentials evoked by stretch of pronator teres, and no C-reflexes. Another patient had myoclonic jerks of the forearm on attempts to write ("myoclonic writer's cramp") that also responded to anticholinergic drugs; EMG activity appeared synchronously or alternating in antagonist muscles. These disorders have features of dystonia and enlarge the spectrum of writer's cramp. PMID- 4022391 TI - Western Norway: a high-risk area for MS. PMID- 4022392 TI - Lyme disease: commentary from Europe. PMID- 4022393 TI - Locked-in syndrome with deafness. PMID- 4022394 TI - Kleine-Levin syndrome: normal CSF monoamines and response to lithium therapy. PMID- 4022395 TI - Muscle mitochondria from patients with Duchenne muscular dystrophy have a normal beta oxidation, but an impaired oxidative phosphorylation. PMID- 4022396 TI - Dynamic computed tomography of the brain. AB - Dynamic computed tomography (CT) scanning was performed on five normal subjects, 38 patients with cerebrovascular disorder, and 20 patients with brain tumours. It consisted of performing six rapid sequential scans after intravenous bolus injection of iodinated contrast medium. By gamma variate fit technique, five features (corrected first moment, area, peak, time to peak, and per cent terminal height) were obtained from a time-density curve in a region of interest. We compared these features in one side of the brain with those in the corresponding contralateral side and tried to get information about cerebral perfusion. These results showed that by this technique we are able to detect arterial occlusions or Moya moya diseases non-invasively and know earlier and more clearly the re establishment of circulation in the occluded arteries and of extravasation of contrast medium in ischaemic regions than by conventional CT scanning. In arteriovenous malformations, serial images of dynamic CT scanning demonstrated the anatomical details of the nidus, and the afferent and efferent vessels. We can also identify an exact extent of tumoral invasion of the brain in patients with malignant brain tumor. PMID- 4022397 TI - Tomographic cerebral blood flow measurement using xenon inhalation and serial CT scanning: normal values and its validity. PMID- 4022398 TI - The technique of direct multiplanar high resolution CT of the temporal bone. AB - The technique of direct multiplanar high resolution CT opens new possibilities for detecting even the smallest lesions of the central nervous system and its coverings. The prerequisites are: Submillimetre spatial resolution. Thin slice thickness collimation. Sufficient radiation dose to keep the noise in the image around about 1%. No waiting time between scans other than short reconstruction times, or use of rapid sequence scan procedures. Possibility to position patients and immobilize them for direct scanning of coronal and sagittal planes without significantly reducing the patient's comfort. Possibility of using optional algorithms which improve spatial resolution further (MacroView) in order to bring out very fine details. This article describes the technique we have used in order to fulfil these prerequisites and also gives a few results relating to the imaging of the facial nerve canal. PMID- 4022399 TI - [Clinical experience with the use of sodium cefoxitin in surgery on the heart and thoracic aorta]. PMID- 4022400 TI - [Rhabdomyolysis in acute heroin poisoning. Report of 2 cases]. PMID- 4022401 TI - [Case of pulmonary edema after treatment with naloxone]. PMID- 4022402 TI - [Scheme for short-term analgesic therapy]. PMID- 4022403 TI - [Immediate and late results of cryo-block of the intercostal nerves and treatment of postoperative pain in thoracic surgery]. PMID- 4022404 TI - [Treatment of pain in acute herpes zoster and post-herpetic neuritis]. PMID- 4022406 TI - [Counterirritation analgesia. Clinical evaluation of the effect of trigger points in chronic non-malignant pain]. PMID- 4022405 TI - [Atypical cholinesterases: investigation using the dibucaine test]. PMID- 4022407 TI - [Can anesthesia be employed for male or female sterilization with impunity?]. PMID- 4022408 TI - [Reassessment of the "full-time" physician for better health care to the citizenry]. PMID- 4022410 TI - [Thrombosis and splenectomy. Preliminary note on the changes of various blood coagulation parameters 20 days after splenectomy. Experimental research]. PMID- 4022409 TI - [Buprenorphine in general anesthesia. I. Preliminary study]. PMID- 4022411 TI - [Bile bacteria and postoperative infective complications]. PMID- 4022413 TI - [Incidence of recurrences in relation to various technics of surgical correction of inguino-femoral hernias]. PMID- 4022412 TI - [911 cases of inguinal and crural hernias systematically treated with a particular technic]. PMID- 4022414 TI - [Ileal perforation caused by metastasis of bronchogenic carcinoma]. PMID- 4022415 TI - [Erythrocyte hexokinases in differentiated adenocarcinoma]. PMID- 4022416 TI - [Deep cervical atypical lipoma]. PMID- 4022417 TI - [Abnormal muscle belly simulating a neoplasm of the palm of the hand]. PMID- 4022418 TI - The clinical value of preoperative indirect systolic ankle pressure measurements in wound healing after amputation of the lower extremity. AB - With the intention towards more distal amputation of the lower extremity for peripheral vascular disease, failure of amputation wound healing remains a common clinical problem. Because calf blood flow correlates well with the indirect systolic ankle pressure, this pressure could be a prognostic guide to the outcome of amputation wound healing. To evaluate the clinical role of systolic ankle pressure measurements for selecting the most appropriate level of amputation, data of 93 patients undergoing 100 amputations were studied retrospectively. Of the 54 initial below knee (BK) amputations 83% healed and 17% failed to heal. Of the 46 initial above knee (AK) amputations 88% healed and 12% needed stump correction. Although all extremities with a systolic ankle pressure of more than 70 mm Hg healed in BK amputations there was no clinical predictive value of indirect systolic ankle pressure measurements. There was no difference in wound healing between diabetic and non-diabetic patients. PMID- 4022419 TI - Is there still a place for Whipple's operation? AB - During a 12 year period 42 patients underwent a pancreatoduodenectomy, on 35 occasions because of malignancy. Four patients (11%), all with pancreatic cancer, died in the postoperative period. Two of the seven patients with pancreatitis died (28%). No patient with pancreatic cancer survived one year. Seven of the 11 patients with distal common bile duct cancer survived one year and five out of seven patients with carcinoma of the ampulla of Vater survived one year. Local tumor recurrence occurred in at least 18 of 27 patients (67%), upper abdominal pain being the most important symptom. At long follow-up three patients had tumor recurrence in the laparotomy scar. In our experience resection offers the only chance of cure for patients with a tumor of the ampulla of Vater or the distal common bile duct. At present, however, resection is not the treatment of choice in patients with pancreatic cancer. PMID- 4022420 TI - The influence of preoperative jaundice, biliary drainage and age on postoperative morbidity and mortality after pancreatoduodenectomy and total pancreatectomy. AB - Details are given of the postoperative course of 56 patients after pancreatoduodenectomy, and 11 after total pancreatectomy. The main indication was adenocarcinoma (56 cases). The most serious complication was leakage from the pancreatojejunostomy, which occurred in nine patients and was fatal in seven of these (10%). This was the only cause of death in the group. The observed mortality was appreciably higher (38%) in the 13 patients aged over 70 years. Contrary to recent reports, jaundice was not found to influence postoperative mortality adversely, nor was preoperative biliary drainage found to reduce mortality. PMID- 4022422 TI - Disengagement of the sliding compression screw in the treatment of intertrochanteric fractures of the femur. PMID- 4022421 TI - Dome fracture of the talus. AB - Three cases of transchondral fracture of the dome of the talus are reported. Two were treated surgically, one conservatively. A review of the literature is presented and the relative values of surgical intervention and conservative therapy are discussed. PMID- 4022423 TI - Fibrosarcoma occurring in scar tissue. PMID- 4022424 TI - Slipping of the upper femoral epiphysis masked by acute appendicitis. PMID- 4022425 TI - [Possibilities and limits of neurosurgery in the management of cerebral ischemia]. AB - Surgical treatment of occlusive cerebrovascular diseases is based on the theory that improved cerebral blood flow in the occluded areas can potentially limit the degree of ischaemic damage. This, it is thought, will at least partially normalise neuron metabolism. The two commonly used surgical techniques are carotid endarterectomy and extracranial-intracranial anastomosis. The importance of the criteria used in selecting patients for surgery is discussed and it is emphasised that the most satisfactory results will only be obtained if the correct surgical indication is carefully established for each patient. The results obtained in 40 carotid endarterectomies and 94 E.I.A.B. are also presented. Mortality and morbidity rates for both procedures are minimal and the results were satisfactory in over 90% of the case, the neurological deficit being corrected or drastically reduced. PMID- 4022427 TI - [Risk factors and acute cerebral infarct in patients selected on the basis of blood sugar levels]. AB - Clinical and laboratory abnormalities were examined in relation to diabetes mellitus in a retrospective study of the 120 patients with acute stroke admitted to our medical unit between January 1, 1981 and March 31, 1984, inclusive. Paretic stroke was defined without clinical evidence of alternative diagnosis. We have examined: age, serum levels of glucose, urea, creatinine, cholesterol, triglycerides, albumin, globulins, ratio albumin/globulins and also a white and red blood-cells count, haemoglobin, erythrocyte sedimentation rate and blood pressure. The routine electrocardiogram (ECG) obtained on admission was examined for atrial fibrillation. The high prevalence of risk factors associated with diabetes mellitus in stroke patients indicate the need for further studies of stroke prevention and treatment particularly in this disease. PMID- 4022426 TI - [Gastrointestinal cancer antigen and carcinoembryonic antigen in chronic pancreatopathies and pancreatic tumors]. AB - Sensitivity and specificity of the Ca 19-9 (GICA) marker was evaluated in series of pancreatic cancer patients, chronic pancreatitis patients and normal controls. When Ca 19-9 was compared with CEA, it was noted that the new marker was far more sensitive and specific than CEA (82% v. 52% sensitivity, 95% v. 80% specificity). GICA was found to be the best marker for pancreatic tumors. PMID- 4022428 TI - [An epidemic focus of tularemia in the Province of Siena]. AB - After a brief account of the epidemiology of tularaemia in Tuscany, a small epidemic focus recorded in the Monte Amiata area in 1982, the first in the Province of Siena, is described. The importance of Mollaret's serum diagnosis for the recognition of current and earlier tularaemia infections is noted. PMID- 4022429 TI - [The natural history of Still's disease. Description of a clinical case with repeated recurrences and long remission periods]. AB - A case of Still's disease is presented that demonstrates the uncertain prognosis and the duration of the treatment required to prevent recurrences. The importance of frequent check-ups is also emphasised. PMID- 4022430 TI - [A new method in the diagnosis of joint pathology: arthroscopy]. AB - A simple new symptomatological technique is described with the emphasis on its great value in the diagnosis of joint pathologies. PMID- 4022431 TI - [Hemorheological, hemocoagulation and photoplethysmographic changes induced by the administration of pentoxifylline in patients with Raynaud's disease]. AB - 1200 mg/day per os of Pentoxyphyllin administered for 60 day brought about an improvement in symptomatology and photoplethysmographic readouts under base conditions and following the cooling test in 7 out of 11 females suffering from Raynaud's disease. These results may be explained by an improved microcirculation flow resulting from increased erythrocyte filterability and a decrease in fibrinogenemia . PMID- 4022432 TI - [Therapy of brucellosis: clinical experience with a rifampicin- doxycycline combination]. AB - After an examination of the data on brucellosis treatment in the literature, it is concluded that short-term courses of cotrimoxazole and tetracyclines give largely unsatisfactory results. In view of the synergism noted between rifampicin and doxycycline against in vitro and animal brucella, the association was given to 19 clinical cases and was found to be effective and easily handled. It is therefore concluded that this treatment is currently the best alternative to the classic streptomycin-doxycycline association. PMID- 4022433 TI - [Behavior of the pressure of the lower esophageal sphincter after intravenous administration of domperidone in normal subjects]. AB - Manometric studies on the action of domperidone 10 mg and 20 mg i.v. on the lower esophageal sphincter pressure (LESP) have been carried on ten healthy volunteers. Domperidone inhibits dopamine receptors and results in an increase of LESP. A dose of 10 mg produces a significant increase in LESP which is rapid and prolonged for thirty minutes; a dose of 20 mg is less efficient. The stimulatory effect of domperidone on LESP suggests an important role for endogenous dopamine as an inhibitory neuromodulator of LES pressure. The use of domperidone in therapy for reflux esophagitis is suggested. PMID- 4022434 TI - [Solitary ulcer syndrome: anatomo-clinical aspects]. AB - The clinical, radiological, endoscopic and histological aspects of a case of Isolated Ulcer Syndrome (IUS) of the rectum are examined. For over a decade and on the basis of its clinical, radiological, endoscopic and histological features, this condition was considered Ulcerous Rectocolitis and treated as such. The case presented serves to highlight the possibility of confusing this ulcer with other inflammatory colorectal conditions if only the clinical, radiological and endoscopic pictures are taken into consideration. The importance of histological examination of numerous bioptic samples is emphasised as essential for accurate diagnosis. PMID- 4022435 TI - [Splenic arrhythmia, a reliable sign of bilio-duodenal pathology]. PMID- 4022436 TI - [Blood uric acid]. PMID- 4022437 TI - [Risk of occurrence of pelvic inflammatory disease correlated with the duration of use of an intrauterine device]. PMID- 4022438 TI - [Intrauterine contraceptive devices and ovarian actinomycosis]. PMID- 4022439 TI - [Efficacy and limits of cerclage according to McDonald in the treatment of cervico-isthmic insufficiency]. PMID- 4022440 TI - [Correlations between the increment of maternal weight and neonatal mortality in a population of low-weight newborn infants]. PMID- 4022441 TI - [Fetal cyclic activity and its neurophysiologic implications]. PMID- 4022442 TI - [Interactions between beta-mimetics and indices of feto-placental function]. PMID- 4022443 TI - [Early diagnosis of endometrial carcinoma. Introduction of hysteroscopy]. PMID- 4022444 TI - Costal and crural diaphragm and intercostal muscle activity during augmented breaths in cats. AB - The pattern of electrical activity of the costal and crural diaphragm and the external intercostal muscles was ascertained in ten anesthetized spontaneously breathing cats during eupnea and during augmented breaths. All muscles studied manifested a biphasic activity pattern during augmented breaths. The increase in activity during the latter portion (phase II) of the augmented breaths was greater for the crural than the costal diaphragm (P less than 0.05), and greater for cranially located intercostal muscles than for the costal diaphragm (P less than 0.02) and more caudally located intercostal muscles (P less than 0.02). These results suggest that during augmented breaths, activity of different thoracic muscles is modulated in a non-uniform manner. PMID- 4022445 TI - Ascending responses induced by transmural nerve stimulation in the cat duodenum. AB - Electromyographic responses of the cat duodenum were recorded in vitro up to 5 cm oral to the site of transmural nerve stimulation. Repetitive stimulation induced ascending cholinergic and non-cholinergic excitatory responses characterized by an increase in the slow wave amplitude and spiking activity. Ascending inhibitory responses were also recorded and were characterized by a suppression of the spiking activity and a decrease in the slow wave amplitude. The ascending cholinergic excitatory response was abolished by atropine. The non-cholinergic excitatory and inhibitory responses both disappeared in the presence of tetrodotoxin. PMID- 4022446 TI - Central determination of recruitment order: intracellular study of phrenic motoneurons. AB - Simultaneous recordings were made intracellularly from phrenic motoneurons (PMs) and extracellularly from their central drivers, the inspiratory bulbospinal neurons (IBSNs) of the dorsal respiratory nucleus. On the basis of their order of recruitment from the beginning of inspiration (as estimated by the phrenic discharge). PMs and IBSNs were classified as early (E) or late (L) units. Unitary excitatory postsynaptic potentials (EPSPs) evoked in the PM by the IBSN were frequently observed between IBSNs and PMs with a similar recruitment, both E, 11/28 or both L, 10/13, and were scarce between IBSNs and PMs with different recruitment. E and L, 8/28, or L and E, 2/11. Since measured membrane resistances of E and L PMs were not statistically different, the recruitment order of PMs may be considered as mainly determined by the timing (E or L) of the central drive that they received. PMID- 4022447 TI - Segmental distribution of afferent fibres in the left inferior cardiac nerve of the cat studied by anterograde transport of horseradish peroxidase. AB - The segmental projection of afferent fibres in the left inferior cardiac nerve of the cat was studied by using the anterograde transport of horseradish peroxidase (HRP). HRP-positive cell bodies were detected in ipsilateral dorsal root ganglia from segments T1 to T7. No labelled neurones were found at segments C8 and T8. The total number of labelled neurones ranged from 157 to 535 neurones in individual experiments. The majority of neurones (70-88%) were localized in the dorsal root ganglia of segments T2-T4. Labelled neurones were oval shaped, and most neurones had a long axis in the range from 20 to 40 microns. PMID- 4022448 TI - Post-trial flicker stimulation interferes with spatial memory in the Morris water maze. AB - Rats (n = 20) trained under monocular viewing conditions in the working memory version of Morris water maze task received daily a single acquisition trial with a new location of the invisible escape platform followed after 15 min by a single retrieval trial. Escape latency decreased by 50% during retrieval. Flash stimulation (20 Hz, 0.6 J) during the entire 15-min delay disrupted retention, but this effect was not observed when the flashes started 3 or 5 min after acquisition. It is concluded that successful place learning requires a brief interference-free post-acquisition interval. PMID- 4022450 TI - Pyrethroids and neuroactive pesticides. Proceedings of the Third International Conference on Neurotoxicity of Selected Chemicals. September 9-12, 1984, Little Rock, Arkansas. PMID- 4022449 TI - In vivo voltammetric determination of the kinetics of dopamine metabolism in the rat. AB - In vivo voltammetry at carbon paste electrodes placed in the striatum of chloral hydrate-anesthetized rats was used to monitor changes in extracellular 3,4 dihydroxyphenylacetic acid (DOPAC) following 1-min periods of electrical stimulation of the ascending nigro-striatal pathways. Statistical analysis of resultant changes in DOPAC allows simultaneous determination of the rate constants for the turnover of both dopamine (DA) (0.046/min) and DOPAC (0.053/min.). The data demonstrate that there are substantial temporal differences between neuronal release of DA and changes in striatal DOPAC levels. This should be considered when metabolite measurements are used as an index of neurotransmitter activity. PMID- 4022451 TI - Physicochemical properties of pyrethroids and specific action-potential changes. PMID- 4022452 TI - Influence of mixed function oxygenase metabolism on the acute neurotoxicity of the pesticide chlordimeform in mice. PMID- 4022453 TI - Two mechanisms of pyrethroid action: electrophysiological and pharmacological evidence. PMID- 4022454 TI - Comparative effects of pyrethroids on neurons of target and non-target organisms. PMID- 4022455 TI - Ascending projections to the lateral thalamic nuclei from the substantia grisea centralis in the rat: a retrograde WGA-HRP study. AB - Ascending projections to the lateral thalamic nuclear group from the substantia grisea centralis (SGC) were studied by injections of wheat germ agglutinin conjugated with HRP (WGA-HRP) into the laterodorsal (LD) and lateroposterior (LP) thalamic nuclei. The present study demonstrated that the pars ventralis of the SGC at the levels of the intercollicular region and of the locus ceruleus sent fibers to both the LD and LP on both sides with homolateral predominance. Distribution pattern and morphological characteristics of the LD-projection neurons in the SGC were similar to those of SGC-LP projection cells. WGA-HRP injections into the LD or LP labeled also a considerable number of neurons in the dorsal raphe nucleus and the dorsal tegmental nucleus bilaterally with homolateral predominance, but the nucleus of Darkschewitsch contained labeled neurons only after the LD injection. PMID- 4022456 TI - Two types of rostroventral medulla neurons projecting to the trigeminal spinal nucleus as differentiated by the response to antidromic activation and the histological location. AB - A population of neurons in the rostroventral medulla, which send their axons to the subnucleus oralis of the trigeminal spinal nucleus of rats, could be differentiated into two types on the basis of their location and the variability of antidromic latency during repetitive stimulation at 10 Hz. Type A neurons were mostly located in the raphe magnus and were activated antidromically with a relatively long latency, which gradually increased during repetitive stimulation. By contrast, type B neurons were located in the medial portion of the gigantocellular reticular nucleus, and responded with a relatively short, stable antidromic latency. PMID- 4022457 TI - Enhancement by estrogen treatment of -bungarotoxin binding in fetal mouse amygdala cells reaggregated in vitro. AB - Dissociated amygdala cells from 17-day-old mouse fetuses were cultivated in a flask for 7 days to form aggregates. In the aggregates there developed typical synaptic structures and [125I]alpha-bungarotoxin binding capacity. An addition of estradiol (100 ng/ml) in the culture medium caused a significant increase in the toxin binding capacity. From these results it is concluded that estradiol enhances alpha-bungarotoxin binding capacity in the amygdala by exerting direct effects on the developing amygdala cells. PMID- 4022458 TI - Topographic organization of projections from the amygdala to the hypothalamus of the rat. AB - Afferent fibers from the amygdala to subdivisions of lateral, ventromedial and dorsomedial hypothalamic nuclei were investigated in rat by retrograde transport of horseradish peroxidase. Small (intranuclear size) peroxidase deposits were placed in hypothalamic nuclei by iontophoresis of a tracer solution containing poly-L-alpha-ornithine which greatly limited diffusion. The medial, central and amygdalo-hippocampal nuclei of the amygdala were found to be the major donors of amygdaloid afferent fibers to the hypothalamus, but there was also substantial labeling of somata in cortical, basomedial, basolateral and lateral amygdaloid nuclei and the intra-amygdaloid bed nucleus of the stria terminalis. No fibers projected from the posterior cortical nucleus of the amygdala to the hypothalamus. Most amygdaloid projections to the lateral hypothalamic area originated in the anterior half of the amygdala, while projections to the ventromedial hypothalamic nucleus arose along the entire length of the amygdala except the posterior cortical nucleus. The amygdalo-hippocampal area projects to the medial hypothalamus. Other amygdaloid nuclei project to both the medial and lateral hypothalamic nuclei. These topographic organizations of amygdaloid afferent fibers to various subdivisions of the hypothalamic nuclei are discussed and compared with other anatomical studies on these connections. PMID- 4022459 TI - Claustral and amygdaloid afferents to the head of the caudate nucleus in macaque monkeys. AB - A single dose of horseradish peroxidase polyacrylamide gel (10%, 1.0 microliter) was injected, after callosotomy, into the head of the caudate nucleus in six macaque monkeys. In addition to the previously reported structures sending fibers to the caudate nucleus, such as the cerebral cortex, substantia innominata, thalamus, hypothalamus, substantia nigra and brainstem, labeled cells were found abundantly in the rostral portion of the ipsilateral claustrum, and fewer labeled cells were dispersed in the ipsilateral external and extreme capsules. Many labeled cells were also present in the ipsilateral insular cortex throughout its rostrocaudal extent. Moreover, labeled cells were seen ipsilaterally in the basolateral, basomedial, accessory basal, and cortical nuclei of the amygdaloid complex. PMID- 4022460 TI - Laminar distributions of neurons sensitive to acetylcholine, noradrenaline and dopamine in the dorsolateral prefrontal cortex of the monkey. AB - Sensitivities of neurons to acetylcholine (ACh), noradrenaline (NA) and dopamine (DA) were investigated at different depths of the dorsolateral prefrontal cortex (PFC) in awake or halothane-anesthetized macaque monkeys, using microiontophoretic techniques with multi-barreled electrodes. The laminar locations of tested neurons (n = 403) were estimated by reconstructing electrode tracks based on the microlesion made by passing a current through the recording barrel, which contained a carbon fiber. Iontophoretically applied drugs induced excitatory or inhibitory responses. Neurons excited by ACh (n = 105) were located mainly in layers III and V, and those inhibited by ACh (n = 126) were in layers III and IV. The majority of the NA-sensitive neurons (n = 123) were NA-inhibited neurons (n = 100), and were found most often in layers III and IV. The ratio of DA-sensitive neurons (excited, n = 74; inhibited, n = 63) to tested neurons was higher in the deep layers than in the superficial ones. These results indicate that sensitivities of the PFC neurons to ACh, NA and DA are not uniform between cortical layers, suggesting that each of these substances may predominantly influence the neuronal activity of particular layers of the monkey PFC. PMID- 4022461 TI - Effects of lesion of the interstitial nucleus of Cajal on vestibular horizontal canal neurons in the cat. AB - Effects of procaine infusion into the interstitial nucleus of Cajal (INC) on vestibular nuclear neurons related to the horizontal canal were studied in cats anesthetized with nitrous oxide and paralyzed with gallamine. Neurons that responded to sinusoidal horizontal rotation (at 0.18 Hz) were recorded extracellularly in the medial and descending vestibular nuclei. Spontaneous activity of type I neurons increased, whereas that of type II neurons decreased following procaine infusion into the ipsilateral INC. Gain of the neuronal response to horizontal rotation decreased after the ipsilateral INC infusion, but there was no consistent effect on phase. Infusion into the contralateral INC seemed less effective. Similar effects were obtained with electrolytic lesions that were confined to the ipsilateral INC area. These results suggest that the INC influences type I neurons through inhibitory action of type II neurons and that it eventually controls the gain, but not the phase, of the horizontal vestibular reflexes. PMID- 4022462 TI - Calcium and vitamin D intakes influence the risk of bowel cancer in men. PMID- 4022463 TI - Breast feeding and child development at five years. PMID- 4022464 TI - Cimetidine inhibits the hepatic hydroxylation of vitamin D. PMID- 4022465 TI - Adverse effects of orally administered tin. PMID- 4022466 TI - Decrease in collagen synthesis due to fasting. PMID- 4022467 TI - New recommendations for high blood pressure control: guidelines for all NPs. PMID- 4022468 TI - Legal parameters of drug prescriptions by NPs. AB - Nurse practitioners' roles are expanding to include greater legal responsibility as caregivers and as expert witnesses in courts of law. Many states allow the expanding role to include the prescription of drugs, usually within a protocol or standing-order framework. Other states prohibit nurses from prescribing drugs. As the responsibilities of nurse practitioners grow, so should their authority to determine what they consider to be nursing practice. It is the purpose of this article to explicate the ways in which the law has treated the subject of drug prescriptions by nurses with a special emphasis on nurse practitioners' responsibilities. PMID- 4022469 TI - Dose rates from patients having nuclear medicine investigations. AB - Dose rates have been measured at 0.1 m, 0.5 m and 1.0 m from patients in a Nuclear Medicine Department. Data are presented for a variety of Nuclear Medicine procedures using doses of radiopharmaceuticals within the recommendations of the administration of Radioactive Substances Advisory Committee (ARSAC). The corresponding figures when the patient left the department, and the time average dose rate over the next 8 h were calculated. At 1.0 m the dose rates do not exceed 7.5 microSv h-1, and at 0.5 m the time average dose rate does not exceed 60 microSv h-1. Assuming that the nurse is as close to the patient as 0.1 m for 20 min in a working day, the accumulated dose over a working day would not exceed 60 microSv. PMID- 4022470 TI - Performance of two new solid-phase ligand assays for TSH using monoclonal antibodies. AB - Three ligand assays for TSH using monoclonal antibodies, an IRMA, an ELISA and a DELFIA were compared with a standard DAB RIA technique. The IRMA proved to be superior in respect to sensitivity, precision, reproducibility and practicality. The highest sensitivity yet, was achieved by DELFIA. IRMA, ELISA and DELFIA are performable on a daily routine basis. ELISA and DELFIA have the additional advantage of being non-isotopic immunoassays (NIIA). Under routine conditions IRMA reveals the best discrimination of hyperthyroid from euthyroid patients by basal TSH. This fact improves the TSH determination's clinical value considerably and may in the future--if confirmed--change the diagnostic schemes in use at present, e.g. rendering most of the TRH-tests unnecessary. PMID- 4022471 TI - Validity of the geometric mean correction in the quantification of whole bowel transit. AB - The accurate interpretation of gastrointestinal transit studies often requires quantification of the data. Particles radiolabelled with indium-111 have been monitored using a gamma camera, during transit through the stomach and the small and large intestines of normal subjects. The count rates measured from either anterior or posterior images alone showed considerable variations, and depended on the site of the tracer within the gut. The geometric mean values of corresponding anterior and posterior count rates remained almost constant throughout each study. PMID- 4022472 TI - Paradoxical phase changes induced by myocardial ischaemia. PMID- 4022473 TI - The dynamic effect of chewing gum on gastric acid secretion. PMID- 4022474 TI - Distribution of 110Ag-silver nitrate prophylaxis solutions following eyedrop application to the albino rabbit. AB - The distribution of radioactive silver-110 labelled silver nitrate in the eye of the albino rabbit was determined by eyedrop application of 1, 2 and 6% solutions. The distribution of the radiotracer was determined at 1 h and 1 day post application. Localization at 1 h was primarily in the cornea and conjunctiva. Washout of this radiotracer was rapid. PMID- 4022475 TI - Female genital mutilation. AB - Genital mutilation of females constitutes a significant health hazard to the emotional and psychological status of women in many parts of the world. The anthropologic, cultural and social rationale for this custom is complex and case specific. The practice of female circumcision is nearly world-wide in its distribution and the extent of the genital alteration varies widely. Attitudes regarding a woman's role in society impact strongly on the acceptance and perpetration of this practice. Health care workers in the western world are encountering female circumcision as world travel becomes more frequently available for Third World citizens. Over 25 per cent of women subjected to the more severe forms of circumcision, i.e., "Pharaonic," suffer serious physical complications. The current status and remedial measures being undertaken in the Sudan and Somalia are reviewed. The question of, why is there any form of genital mutilation for either sex, is raised. PMID- 4022476 TI - Amniotic fluid embolism. Three case reports with a review of the literature. AB - Amniotic fluid embolism is a catastrophic event of the intra- and early postpartum period which may also be seen with cesarean delivery and during abortions. Presenting symptomatology includes respiratory distress with cyanosis, shock, and possibly tonic-clonic seizures. DIC frequently occurs. The pathogenesis may include entry of amniotic fluid through lacerations or ruptures of the uterus or cervix, through endocervical veins and through abnormal uteroplacental sites, such as with placental abruption, placenta previa, or placenta accreta. Amniotic fluid probably causes cardiovascular-respiratory symptoms by pulmonary vascular obstruction and through a vasoactive substance causing pulmonary vascular constriction. The lethality of amniotic fluid may be enhanced by a high particulate content or meconium staining. The diagnosis of amniotic fluid embolism may be made ante mortem by demonstrating amniotic fluid debris in central blood samples or expectorated sputum. Postmortem diagnosis often requires meticulous examination of the pulmonary microvasculature with the utilization of special stains. Treatment is directed towards symptoms of shock, arterial hypoxemia, and DIC. Acute renal failure may complicate the picture after shock. If the patient survives the embolic and coagulative problems, recovery is usually complete without long-term sequelae. PMID- 4022477 TI - Ovarian abscess. Report of a case and a review of the literature. PMID- 4022478 TI - Macrosomia--maternal characteristics and infant complications. AB - Using a 1982 to 1983 regional network data bank of 33,545 delivered infants, a study was conducted comparing 574 macrosomic infants weighing greater than 4500 g to a control group of 18,739 infants whose birth weights were 2500 to 3499 g. Macrosomic infants occurred in 1.7% of the deliveries. Women delivering macrosomic infants were significantly older, of higher parity, more obese (greater than 90 kg), and more frequently diabetic and postmature (longer than 42 weeks) than the controls. The women having macrosomic infants had a higher frequency of cesarean deliveries. The macrosomic infants were more often male and had more birth trauma and shoulder dystocia, higher death rates, and lower Apgar scores. Five-minute Apgar scores were lowest in the very macrosomic subgroup (greater than 5000 g). The high-risk group triad included obesity, diabetes, and post-dates and had a macrosomia frequency of 5 to 14%. Macrosomic infants delivered by cesarean section had significantly fewer birth injuries. Because of these serious perinatal problems, women at risk should be screened for macrosomic infants, and if found, they should be delivered electively by cesarean section. PMID- 4022479 TI - Use of beta-methasone in management of preterm gestation with premature rupture of membranes. AB - Use of corticosteroids in the management of rupture of the membranes in a preterm gestation was evaluated. Ninety-three mothers (105 infants) received beta methasone, whereas 105 mothers (112 infants) did not. The incidence of significant neonatal respiratory complications was statistically higher for beta methasone-treated (26.6%) compared with non-treated patients (11.1%) who delivered more than 48 hours after rupture of membranes. Neonatal septic complications also were significantly higher in treated (21.3%) than in nontreated (9.2%) patients delivered 48 hours after rupture of membranes. Maternal sepsis was not statistically different between the two groups. In the nonsteroid-treated patients, the incidence of significant respiratory distress syndrome was greater for those infants delivered within 48 hours (31.0%) than those delivered more than 48 hours (11.1%) from rupture of membranes. The data support conservative management and indicate that corticosteroid administration in a preterm gestation with rupture of membranes is not beneficial to the newborn. PMID- 4022480 TI - A five-year experience with terbutaline for preterm labor: low rate of severe side effects. AB - The medical records of 330 patients treated with terbutaline infusion for the inhibition of preterm labor were reviewed over a five-year period. In patients with intact membranes the results were uniformly good, particularly when treatment was instituted before the 30th week. Half these patients had a prolonged labor of six weeks or more; in most cases of treatment failure complications already existed on admission. In only nine patients (2.7%) terbutaline treatment was stopped due to side effects: predominantly maternal tachycardia or vomiting. Two patients had chest symptoms, but in no case was pulmonary edema diagnosed. The results suggested that a low incidence of severe side effects can be obtained if the following precautions are taken: glucose is used as the infusion medium, instead of sodium chloride; concentrated solutions are given to avoid fluid overload; the patients are carefully controlled; and the infusion is immediately reduced or stopped if signs of severe side effects appear. PMID- 4022481 TI - Physical abuse in pregnancy. AB - Screening interviews to determine the extent of physical abuse were conducted for 742 women seen in the University of Virginia obstetric clinics. Eighty-one women (10.9%) reported that they had experienced abuse at some point in the past. These women were more likely to be divorced or separated, indigent, and less educated than were the non-abused control patients. They were more likely to have had emotional problems, and 20% had attempted suicide. Twenty-nine of the 81 women reported abuse during the current pregnancy, with 21% reporting increased abuse and 36% noting decreased abuse during pregnancy. Women living with an abusive partner did not experience a greater frequency of adverse pregnancy outcomes than did those who had left abusive relationships. An awareness of the extent of the problem and direct questioning will result in an increased identification of women who are at risk for physical abuse during pregnancy. PMID- 4022482 TI - Fetal tachycardia as an indicator of maternal and neonatal morbidity. AB - Presented is a prospective, controlled study to determine if intrapartum fetal tachycardia is reliable as an indicator of maternal and fetal infectious morbidity. Thirty neonates with defined intrapartum tachycardia were matched by gestational age and weight with 30 control subjects without defined tachycardia. There was a significant difference in maternal febrile morbidity and a trend toward a difference in maternal infectious morbidity between the two groups. There was no significant difference in maternal complications at delivery or administration of antibiotics to the mother. Among the neonates, there was a significant difference in administration of antibiotics and the incidence of respiratory distress syndrome (RDS) between the two groups; however, both of these were significantly related to birth weight. There was no significant difference between the two groups in duration of ruptured membranes, duration of labor, number of vaginal examinations, or antepartum anemia. Only one study infant had a bacteremia. The data confirm an increased risk of neonatal complications, such as RDS, asphyxia, and meconium aspiration, in association with intrapartum fetal tachycardia. PMID- 4022483 TI - Effect of anesthesia for repeat cesarean section on postoperative infectious morbidity. AB - It has been suggested that general anesthesia is a risk factor for postcesarean infectious morbidity. A retrospective review of 206 women who underwent repeat cesarean delivery at Duke University Medical Center was conducted. Group 1 consisted of 106 patients whose repeat cesarean section was performed with regional anesthesia, and group 2 included 100 patients whose repeat cesarean section was performed with general anesthesia. Group 2 patients were more likely to be of low socioeconomic status. There were no statistically significant differences between the two groups with regard to multiple indexes of postoperative fever or infection, including febrile morbidity, diagnosis of infection, use of therapeutic antibiotics, fever index, and postoperative hospital stay. General anesthesia, as administered to patients in the present series, does not increase the risk of infectious morbidity after repeat cesarean delivery. PMID- 4022484 TI - Effects of intravenous ritodrine on lactate and pyruvate levels: role of glycemia and anaerobiosis. AB - The role of glycemia in ritodrine-induced hyperlactatemia was assessed by measuring lactate and pyruvate levels and studying glycemia in patients treated with intravenous ritodrine for premature labor. Lactate levels were increased moderately by ritodrine and paralleled the levels of glucose; a similar parallelism also was observed in the glucose-administration group. Pyruvate levels also changed in proportion to lactate levels in this latter group, whereas in patients given ritodrine, pyruvate changed little and the lactate/pyruvate ratio was increased. These findings are discussed in terms of possible metabolic and vasopressor consequences of beta-adrenergic stimulation, with emphasis on the potential roles of increased glycemia and anaerobiosis. PMID- 4022485 TI - Postmenopausal uterine bleeding of nonorganic cause. AB - Eighty-nine patients with postmenopausal uterine bleeding were studied focusing on the nonorganic causes of bleeding. Atrophic endometrium was found in 82%, proliferative endometrium in 7%, and secretory endometrium in 1% of patients. Carcinoma was uncommon, found in only 7% of patients. Hysteroscopy was an invaluable adjunct to dilatation and curettage in diagnosing bleeding due to atrophic endometrium as 42% of such cases yielded no tissue on curettage. The clinical entity of bleeding atrophic endometrium is discussed. PMID- 4022486 TI - Prevalence of Chlamydia trachomatis in the pregnant cervix. AB - To determine the prevalence of infection and colonization with Chlamydia trachomatis in pregnant women of low socioeconomic status, 363 women (age range 15 to 48 years; median age 24) were screened. Cultures for C trachomatis were obtained prospectively. Chlamydia trachomatis was recovered from 16.8% of the patients. The incidence of infection ranged from 18.4% in the group age 15 to 19 through 13% in the group age 30 to 39, to 0% in the 40 and older group. Thus, in the population studies, C trachomatis was found more commonly in the younger age groups. The high isolation rates seen suggest that routine screening and treatment may be warranted to prevent spread of C trachomatis infections to sexual partners and neonates. PMID- 4022487 TI - Initial evaluation of an ambulatory system for home monitoring and transmission of uterine activity data. AB - A system capable of ambulatory home monitoring of uterine activity and data transmission was evaluated in a group of pregnant patients. The evaluation focused on three questions: 1) Is the information as reliable as that obtained by the current stationary monitors; 2) Does the information obtained by the tested system relate to that obtained by direct intrauterine pressure measurements; and 3) Is the system simple enough to be used by the unsupervised gravida at home? The results indicate that the tested system can provide reliable information about uterine activity in ambulatory patients. A good correlation between the intensity of contractions and the recording of uterine activity by this system could be demonstrated, particularly in the presence of mild to moderate contractions. The tested monitor proved to be simple to use even in the untrained gravida. Additional studies to determine the role of ambulatory home monitoring of uterine activity in patients with cervical cerclage, placenta previa, and preterm labor will need to be performed to establish its role in current obstetric practice. PMID- 4022488 TI - Familial occurrence of mature ovarian teratomas. AB - It has been suggested that genetic predisposing factors play a role in the development of ovarian teratomas. Familial occurrence of these tumors would support this view. Reported herein are identical twins, both of whom had a right ovarian mature teratoma. In both cases the presenting symptoms were acute torsion. The diagnosis was confirmed at laparotomy and subsequent histopathologic examination. The origin of ovarian teratomas seems to be linked to the process of parthenogenesis. This process probably involves a germ cell after its first meiotic division. PMID- 4022489 TI - A technique for uterine conservation in adolescents with vaginal agenesis and a functional uterus. AB - Vaginal agenesis in association with a functional uterus occurs infrequently, and usually presents in adolescents. To preserve reproductive function, the uterus must be conserved, and a vagina must be constructed in one operative procedure. The authors describe a surgical technique that combines a modified McIndoe vaginoplasty with uterine conservation in which a special stent is fabricated to insert in the uterine cervix and the neovagina. Factors that must be considered when choosing between a hysterectomy and a uterine conservation procedure also are discussed. PMID- 4022490 TI - Uterine rupture and epidural anesthesia. PMID- 4022492 TI - Plastic (Bleier) clip high failure rate. PMID- 4022491 TI - Catastrophic uterine rupture. PMID- 4022493 TI - Accurate gestational dating. AB - Gestational age by four ultrasonic parameters (biparietal diameter, head circumference, abdominal circumference, and femur length) was calculated for 210 normal obstetric patients divided into four gestational age groups based on time of first ultrasound examination. Accuracy of the calculations was determined by comparison of each technique and a simple arithmetic average of the four techniques to the gestational age calculated from the Dubowitz examination of the neonate after delivery. The analysis indicated that each ultrasonic technique has certain advantages and disadvantages, but that the simple arithmetic average of the four techniques had the lowest systematic and random error. PMID- 4022494 TI - Lung profile: sex differences in normal pregnancy. AB - The incidence of respiratory distress syndrome (RDS) is higher in male than in female infants. The lung profiles--lecithin/sphingomyelin (L/S) ratios, percent disaturated (acetone precipitated) lecithin, phosphatidylglycerol, and phosphatidylinositol--were obtained in amniotic fluid during 164 normal pregnancies of 30 or more weeks' gestation. The profiles were evaluated to determine any sex differences in fetal development of the surfactant components. According to regression analysis the L/S ratios for females reached 2:1 at 33.7 weeks, which is 1.4 weeks earlier than males. A similar trend was evident for disaturated lecithin. Phosphatidylglycerol first appeared at 34 weeks' gestation for females and 35 weeks for males. The rate of the increase in phosphatidylglycerol was higher in females than in males. Phosphatidylinositol began to decrease after 36 weeks for females and fell to levels below that of males after 37 weeks' gestation. All four indexes of the lung profile revealed a higher degree of lung maturity in female than in male fetuses during the last two months of normal pregnancy. This explains a higher incidence of RDS in male than in female infants. PMID- 4022495 TI - Preeclampsia/eclampsia: hemodynamic and neurologic correlations. AB - Three patients with eclampsia and four with severe preeclampsia underwent pulmonary artery catheterization before either labor or significant volume infusion. There was no difference in systemic or pulmonary vascular resistance, cardiac index, left ventricular stroke work index, or any other hemodynamic parameters between the eclamptic and severely preeclamptic patients. Despite the small numbers, plasma colloid osmotic pressures were significantly lower in the eclamptic patients. Factors other than the intensity of peripheral vasospasm may primarily affect the occurrence of grand mal seizures in patients with preeclampsia. PMID- 4022496 TI - Pregnancy related to infertility diagnosis, number of attempts, and age in a program of in vitro fertilization. AB - Three hundred nineteen infertility patients who did not become pregnant with standard therapies presented to Norfolk for in vitro fertilization between January 1981 and December 1983. There were 560 laparoscopic cycles with 105 pregnancies. The pregnancy rate was 18.8% by cycle, 24.5% by transfer, and 33% by patient. The overall pregnancy rate was found to be independent of infertility diagnosis, age, and number of attempts. PMID- 4022497 TI - Malignant melanoma of the vulva. AB - During the years 1969 to 1982, 16 patients with primary malignant melanoma of the vulva were entered into the Tumor Registry at the University of Miami Jackson Memorial Medical Center. The mean age was 55, with a range of 18 to 89 years. Treatment was primarily by radial vulvectomy with bilateral groin and pelvic node dissection. Survival was correlated to FIGO staging, Clark and Breslow classifications, and lymph node involvement. Survival correlated best to tumor thickness and Clark levels. Patients with Clark level 2 or less and less than 1.5 mm depth of penetration had the best prognosis. Lymph node involvement was present in 25% of the patients, and there were no survivors in this group. There were no instances of positive pelvic nodes when the groin nodes were negative, and routine pelvic lymphadenectomy is not recommended. PMID- 4022498 TI - Prognostic significance of groin lymph node metastases in squamous carcinoma of the vulva. AB - A retrospective review of the clinical and histologic findings in 48 cases of stages I, II, and III (excluding T3) squamous carcinoma of the vulva with positive groin nodes reveals the prognostic significance of the size and number of the nodal metastases. Other factors such as the morphology of the lymph nodes and the histologic features of the primary neoplasm are not nearly as significant. Patients with only one or two small nodal metastases have an excellent outlook for survival providing that adequate margins can be obtained around the primary tumor and that thorough groin node dissections can be performed. These patients do not appear to need adjuvant radiation or pelvic node dissection. A further finding is that patients with unilateral labial carcinomas do not have metastases to the opposite groin in the absence of ipsilateral groin metastases, although six of 21 patients had metastases to both groins. PMID- 4022499 TI - Microglandular hyperplasia of the uterine cervix. AB - Forty-three cases of microglandular hyperplasia of the cervix seen during a 3.5 year period are reported. The series is unusual in that more than one-half of the patients had no history of oral contraceptive use and three patients were postmenopausal. Additionally, evidence of estrogenic stimulation was present in eight cases. The role of estrogens and progestogens in the development of microglandular hyperplasia is discussed. The authors consider microglandular hyperplasia to be an unusual and florid form of reserve cell hyperplasia with glandular differentiation. PMID- 4022500 TI - Comparison of clinical and surgical-staging in patients with endometrial carcinoma. AB - The preoperative clinical and radiologic findings and staging were compared with the operative and pathological findings and surgical staging in 62 consecutive patients with endometrial carcinoma. Overall, the tumor grade was changed in 33.8% of the patients, and the histologic type of tumor was changed in 27.4% of the patients. The preoperative clinical staging was changed in 51% of the patients after surgery. The change for the stage was as follows: stage I, 30.4%; stage II, 62.5%, stage III, 60%; and stage IV, 0%. The endocervical curettage was found to have a 50% false-positive rate and a 13% false-negative rate. PMID- 4022501 TI - Conservative treatment of borderline ovarian tumors. AB - Of 61 patients with stage IA borderline ovarian tumors, 41 were treated with total abdominal hysterectomy and bilateral salpingo-oophorectomy, and 20 were treated by a variety of more limited operations, including cystectomy with (one patient) and without (three patients) a contralateral ovarian wedge biopsy, and unilateral salpingo-oophorectomy with (six patients) and without (ten patients) a contralateral wedge biopsy. In the group treated conservatively, there were 11 serous, seven mucinous, and two mixed seromucinous borderline tumors, whereas in the total abdominal hysterectomy and bilateral salpingo-oophorectomy treatment group there were 26 serious, 12 mucinous, and three mixed seromucinous borderline tumors. After a mean follow-up of 89 months (range 36 to 244 months), subsequent borderline neoplasms had developed in three patients (15%) with serious borderline tumors initially treated conservatively and in two patients (5%) with serous or mixed seromucinous borderline tumors initially treated with total abdominal hysterectomy and bilateral salpingo-oophorectomy. No patient with a mucinous borderline tumor treated either conservatively or with total abdominal hysterectomy and bilateral salpingo-oophorectomy developed a subsequent neoplasm. All 61 patients in the study group are alive and free of disease, including those who developed recurrent neoplasm. PMID- 4022502 TI - Histopathologic correlations of estrogen and progestin receptor protein in epithelial ovarian carcinomas. AB - One hundred thirteen primary epithelial ovarian cancers were analyzed for estrogen and progestin receptor content and the results compared with multiple histologic parameters (grade, necrosis, fibrosis, lymphocyte infiltration, mitoses, tumor giant cells, psammoma bodies, stroma). Grade 4 cancers had a statistically greater likelihood of containing estrogen receptors (P = .03) than did lower grade cancers. However, grade 3 tumor samples containing abundant (3+ and 4+) mitoses had a significantly greater number of estrogen receptor negative cancers (P = .01) than did cancers containing none to moderate (0-2+) mitoses. The only histologic parameter that demonstrated any statistically significant association with progestin receptor content was the presence of lymphocyte infiltration. Samples demonstrating moderate (2+ and 3+) lymphocyte infiltration had a significantly (P = .005) greater chance of being progestin receptor negative than cancers containing none to minimal (0 to 1+) lymphocyte infiltration. This study suggests that estrogen and progestin receptor content of epithelial ovarian cancers is associated with grade and mitoses (estrogen receptor) and lymphocyte infiltration (progestin receptor). With the exception of these relationships, the estrogen and progestin receptor content of ovarian cancers appears independent of all of the histologic parameters examined. PMID- 4022503 TI - New multipronged fetal scalp electrode: a preliminary report. AB - Presented is a preliminary report of the use of a new type of scalp electrode (patent pending), which, because of its design, may have the advantage of improved safety. It was used on 40 patients in labor. To confirm the quality of the recording, in all cases, a fetal electrocardiogram was also obtained. Application was achieved on the first attempt in 37 cases in two additional cases on the second attempt. There were no reported cases of the electrode being dislodged during labor. The quality of the recording was reported to be good. There were no reported cases of trauma to the fetal scalp nor were there any cases of infection noted. PMID- 4022504 TI - Effects of thermal knives on wound healing. AB - Tissue response to injury caused by the electrosurgical scalpel, the hemostatic Shaw scalpel, the CO2 laser, and a standard steel scalpel have been compared. Subcutaneous incisions in pigs were evaluated histologically at 1, 4, 7, 14, and 22 days postincision. The least damage was produced by the standard steel scalpel at all time periods. Epithelial migration started on day 1 for the standard steel scalpel, on day 4 for the Shaw scalpel, and only on day 7 for the electrosurgical scalpel and laser knives. Lateral thermal necrotic zones were found for all three thermal knives. Tensile testing showed no significant differences in the early postincision tissue strength. By day 14 wounds made with the standard steel scalpel were stronger than those made with the Shaw and electrosurgical scalpel. These findings indicate that thermal injury delays the wound healing process. PMID- 4022505 TI - Intraoperative ultrasound for gynecologic procedures. AB - Recent technological advances in portable dynamic imaging equipment allow for the performance of intraoperative ultrasound examinations during certain gynecologic procedures. Reported is the authors' technique for such an examination and outlined are specific vaginal and abdominal gynecologic procedures wherein adjunctive ultrasound may facilitate performance of the operative procedure, enhance safety, and decrease the possibility of complications. PMID- 4022506 TI - Perinatal ethics: a practical method of analysis of obligations to mother and fetus. AB - The ethical principles of beneficence and respect for autonomy enable the physician to identify and consider seriously moral conflicts in modern obstetric care. The authors identify four types of conflicts, provide an analysis of them, and suggest strategies for resolving them in clinical practice. PMID- 4022507 TI - Piperacillin versus clindamycin plus gentamicin for pelvic infections. PMID- 4022508 TI - Estriol versus nonstress testing. PMID- 4022509 TI - Maternal liver impairment associated with prolonged high-dose administration of terbutaline for premature labor. AB - Widespread use of beta 2-sympathomimetic therapy for premature labor has resulted in a diverse number of serious maternal complications, ie, pulmonary edema, myocardial ischemia, etc. However, to the authors' knowledge, there has been only one previous report of mild maternal liver impairment associated with this therapy. Recently, a patient developed marked elevation of liver enzymes (serum glutamic oxaloacetic transaminase, serum glutamic pyruvic transaminase) during therapy with terbutaline sulfate for premature labor. PMID- 4022510 TI - Toxemia in a patient with none of the standard signs and symptoms of preeclampsia. AB - A case of gravida presenting with upper abdominal pain, an elevated serum glutamic oxaloacetic transaminase level, and thrombocytopenia, all of which resolved promptly after delivery, and with none of the standard signs and symptoms needed for the diagnosis of preeclampsia is presented. The issues of how this case relates to preeclampsia, nomenclature, differential diagnosis, and management are discussed. PMID- 4022511 TI - Fetal heart rate decelerations after oxytocin infusion in an abdominal pregnancy. AB - Fetal heart rate (FHR) decelerations during a contraction stress test are recognized as signs of possible uteroplacental insufficiency. Although these decelerations have been described commonly in intrauterine pregnancies, they have not been noted in extrauterine pregnancies. Reported herein are FHR decelerations associated with oxytocin infusion in an extrauterine pregnancy and a discussion of the possible pathophysiologic mechanisms. PMID- 4022512 TI - Hydrops from reciprocating atrioventricular tachycardia in a 27-week fetus requiring quinidine for conversion. AB - A 27-week fetus with severe nonimmune hydrops was found to have a reciprocating atrioventricular tachycardia with the rate of 275 beats per minute. Maternal digitalization produced improvement without conversion. Large doses of propranolol were without effect. Twelve days later quinidine was added, and conversion to sinus rhythm occurred after only two hours and persisted to term. The infant has no heart disease. Literature review confirms digoxin as the first choice for treatment of fetal reciprocating tachycardia, with excellent transplacental passage. Propranolol has not been demonstrably effective, and has poor placental passage. Verapamil also produced poor cord blood levels in two trials. Placental passage for procainamide is uncertain, but long-term use has been unsatisfactory. Quinidine is recommended as the second drug for treatment of resistant fetal tachyrhythmias. PMID- 4022513 TI - Neonatal apnea associated with maternal clonazepam therapy: a case report. AB - A 2750-g female infant was born at 36 weeks' gestation to a 40-year-old woman treated with clonazepam throughout her pregnancy. The infant developed apnea, cyanosis, and hypotonia within a few hours of birth. The mother's serum clonazepam level at delivery was 32 ng/mL; the cord blood level was 19 ng/mL. The infant had no congenital malformations, evidence of infection, or seizures. Clinical episodes ceased by ten days of age. The woman elected to breastfeed; breast milk clonazepam levels were between 11 and 13 ng/mL. She was discharged with a cardiorespiratory monitor. The authors suggest that infants of mothers receiving this agent during pregnancy or while nursing have serum levels measured. Additionally, these infants should be monitored for central nervous system depression or apnea. PMID- 4022514 TI - Pruritus and hyperplacentosis. AB - Hyperplacentosis refers to the maternal manifestations of increased placental activity, such as elevated human chorionic gonadotropin, theca luteal cysts, preeclampsia, and/or pruritus. Six cases of apparent hyperplacentosis were diagnosed in the third trimester because of maternal complaints of pruritus. The association of maternal or fetal complications with hyperplacentosis is described. PMID- 4022515 TI - Intravenous immunoglobulin in pregnancy. AB - A woman with variable hypogammaglobulinemia was treated with an intravenous immunoglobulin preparation during pregnancy. The immunoglobulin G1, 2, and 3 subclasses were all transferred to the fetus. PMID- 4022516 TI - Class H diabetes and pregnancy. AB - Class H diabetes is defined as the presence of diabetes of any duration associated with ischemic myocardial disease. Because of a lack of experience with the coexistence of myocardial ischemic disease and diabetes during pregnancy, it is difficult to offer patients an accurate prognosis for mother and infant during such a gestation. Previous reports suggest that outcomes in this situation are almost routinely poor. It is likely, however, that there is a subset of patients within the class H diabetic population in whom pregnancy can be successful. Reported are the pregnancies of three such patients. The authors suggest that careful attention to cardiac status and glycemic control contribute to both maternal and fetal well-being. Prepregnancy screening of class H patients for evidence of cardiac dysfunction may allow for the screening of those class H diabetic women who are most likely to achieve successful pregnancy outcome. PMID- 4022517 TI - Successful treatment of maternal septicemia due to Listeria monocytogenes at 26 weeks' gestation. AB - A case of successful therapy with ampicillin of maternal septicemia due to Listeria monocytogenes at 26 weeks' gestation with resultant delivery at term of a normal neonate is reported. The ability to positively influence the outcome of hematogenously acquired maternal-fetal infection is stressed. PMID- 4022518 TI - Plasmapheresis for the treatment of repeated early pregnancy wastage associated with anti-P. AB - It has been proposed that the blood group antibody, anti-P, produced by p or Pk individuals may cause abortion early in pregnancy. The authors have studied and successfully treated a Pk woman with anti-P who had 13 consecutive first trimester miscarriages. Anti-P was implicated as the cause of repeated pregnancy loss after extensive clinical, endocrinologic, immunologic, and chromosomal evaluations. To remove P blood group antibodies, plasmapheresis was begun at five weeks' gestation during the 14th pregnancy with one plasma volume exchange two to three times per week. This therapy resulted in a reduction in the titer of anti P, and the patient was delivered of a viable female infant after 33 weeks' gestation. The management and outcome indicate that habitual abortion presumably due to anti-P can be successfully treated with plasmapheresis. This case provides additional evidence that anti-P is responsible for abortions in p or Pk women, and that these abortions are immunologically mediated. PMID- 4022519 TI - A case of endometriosis of the lung treated with danazol. AB - A 25-year-old Japanese woman, complaining of catamenial hemoptysis and severe cough complicated with menorrhalgia, was diagnosed as having pulmonary and pelvic endometriosis. She was treated with danazol for 20 weeks. Significant improvement of her condition was achieved during the treatment period. Catamenial hemoptysis recurred at the first menstruation after termination of the treatment. Readministration of danazol was refused. Therefore, surgical removal of the affected lobe of the right lung was performed. Cases of this rare disorder are reviewed. PMID- 4022520 TI - Endometriosis associated with ascites. AB - Pelvic endometriosis associated with massive ascites is an unusual occurrence. Only 12 cases have been reported since 1954 when Brews first described this entity. The authors present two cases recently encountered at Saga Medical School Hospital. Clinical courses and operative findings are described and other cases from the literature are reviewed. The possible etiologic mechanisms of the ascites are explored and the possibility of conservative surgery and hormonal therapy with danazol is discussed. PMID- 4022521 TI - Primary breast cancer of the vulva. AB - Adenocarcinoma originating in a focus of mammary tissue in the vulva is an extremely rare occurrence. Only three such cases have been reported in the literature. Herein, the fourth example of a primary cancer developing in vulvar mammary tissue is described. Extension to regional lymph nodes is documented, as well as the presence of estrogen receptors in this tumor. Immunohistochemical evidence is rendered supporting an origin from mammary anlage. PMID- 4022522 TI - Chronic granulomatous disease in pregnancy. AB - The ability of phagocytes to kill certain bacteria is impaired in chronic granulomatous disease. This results in frequent infection in the childhood period and frequent death in the early teens. Survival beyond this period is rare and often occurs in patients who have a mild variant of the disease. Reported herein is the obstetric course of a patient with chronic granulomatous disease. PMID- 4022523 TI - Vaginal hemangiopericytoma: a histopathologic and ultrastructural evaluation. AB - The hemangiopericytoma is an uncommon stromovascular neoplasm that arises from the pericyte of Zimmerman. Since their original description in the female genital tract in 1954, the majority of these lesions have been of uterine origin. Presented is a clinicopathologic description of a hemangiopericytoma arising in the vagina and occupying the rectovaginal septum. Light and electron microscopic characterization is rendered. Current understanding of these lesions is reviewed and therapeutic options are discussed. PMID- 4022525 TI - Firefighters face unknowns in right-to-know protection. PMID- 4022524 TI - Peritoneal carcinomatosis after prophylactic oophorectomy in familial ovarian cancer syndrome. AB - A woman who was at high risk for ovarian cancer because of a strongly positive family history underwent prophylactic oophorectomy, but subsequently developed and died of intraabdominal carcinomatosis. One small focus of adenocarcinoma was found on the ovarian surface in serial sections performed retrospectively on the resected ovaries. This case study emphasizes the importance of thorough histologic examination for familial ovarian cancer syndrome, including serial sectioning of the specimens removed in prophylactic oophorectomy. PMID- 4022526 TI - Asbestos. PMID- 4022527 TI - Worksite economical setting for preventive health care programs. PMID- 4022528 TI - Stress release: emerging tool in total stress management program. PMID- 4022529 TI - Chemical protective clothing: laboratory vs. field performance. PMID- 4022530 TI - Going the extra "foot" for workers involves more than measuring stick. PMID- 4022531 TI - Hearing protection for industry: types, selection vary with needs. PMID- 4022532 TI - Chemical protective clothing: the influence of federal agencies. PMID- 4022534 TI - Medical lab services can help find employee chemical exposure. PMID- 4022533 TI - Organizations must be aware of hazardous material regulations. PMID- 4022535 TI - Promising diagnostic technique: nuclear magnetic resonance imaging. PMID- 4022536 TI - Physicians must practice quality care and cost control. PMID- 4022537 TI - Workforce drug abuse takes on new dimension for health profession. PMID- 4022538 TI - Right-to-know deadline approaches requiring material safety data sheets. PMID- 4022539 TI - An experimental study of the longest tolerable time of the total portal triad occlusion in normothermia in rabbit. PMID- 4022540 TI - Free scapular flap for repair of soft tissue defects of extremities. PMID- 4022541 TI - Retrograde cholangiography using double balloon 3 lumen silicon T tube both before and after inflation and its clinical significance--self-control analysis. PMID- 4022542 TI - Glycogen-rich clear cell carcinoma of the breast: a light and electron microscopic study. PMID- 4022543 TI - Studies on myocardial protection by cold fluorocarbon (made in China) cardioplegic solution: experiment on isolated rabbit heart. PMID- 4022544 TI - Effect of hyperthermia induced by environmental heat stress on vascular interoceptor reflexes. PMID- 4022545 TI - Enteric administration of anisodamine in the treatment of hemorrhagic shock. PMID- 4022546 TI - On malathion binding to tissue macromolecules in the rat. PMID- 4022547 TI - Inflation: symptom or disease? PMID- 4022548 TI - Human experimentation. Is it ethical? PMID- 4022549 TI - Placing a value on human life. PMID- 4022550 TI - Ethics and the elderly--care at what cost? PMID- 4022552 TI - Reflections on a teaching experience. PMID- 4022551 TI - World health. Who is responsible? PMID- 4022553 TI - Lyme disease--a new rheumatologic disorder. PMID- 4022554 TI - Pericarditis associated with Crohn's disease. PMID- 4022555 TI - [Application of synergetics to the theory of ontogenesis (on the parametric control of development)]. AB - Applications of synergetics to ontogenesis are discussed. In terms of synergetics, the choice between the concepts of power and parametric control and the description of parameters and dynamic variables of ontogenesis are among the main tasks of the theory of ontogenesis. Examples are provided for multipotency and variability which suggest the parametric control of development. A suggestion is put forward concerning the parameterizing role of directive inductors. Possible ways of overcoming the ambiguity inherent in the parametric control are considered. A general scheme of the ontogenesis control is proposed within the framework of which different types of parameters and dynamic variables are characterized. The concept of chaos is discussed with reference to ontogenesis. PMID- 4022556 TI - [Interspecies chimeras of mammals]. AB - Chimaeras between closely related and distant mammalian species were obtained during the last decade using the aggregation and injection methods. In the chimaeras between the closely related species Mus musculus--M. caroli, the cell clones of both parental species are equally represented; such chimaeras are fertile and their development does not differ from that of intraspecific chimaeras. But in the chimaeras between distant species mouse--rat or sheep--goat a selective predominance of cells with one genotype over those with another was noted. This leads to the total elimination of cell populations with one genotype, rat in particular in the mouse--rat chimaeras, or, possibly, to the sterility of the sheep--goat chimaeras. PMID- 4022557 TI - Painful bullous keratopathy following pediatric cataract surgery with intraocular lens implantation. AB - A child with a history of a monocular congenital cataract, cataract surgery and intraocular lens implantation at age three developed pseudophakic bullous keratopathy which persisted following intraocular lens removal and vitrectomy two years later. At age nine she presented to the Cornea Service at Wills Eye Hospital with painful bullous keratopathy and underwent a penetrating keratoplasty and anterior vitrectomy. The case is presented to bring attention to potential long-term corneal complications of pediatric cataract surgery with intraocular lens implantation. PMID- 4022558 TI - Congenital absence of the superior oblique tendon in craniofacial dysostosis. AB - Absence of each of the extraocular muscles as a rare cause of strabismus has been reported. Helveston suggests that a significant horizontal deviation with suppression and/or amblyopia in a patient with the preoperative diagnosis of congenital superior oblique palsy should alert one to a possible absence of the superior oblique tendon. We present and discuss two patients with craniofacial dysostosis in whom extensive surgical exploration showed an absence of the superior oblique tendon. PMID- 4022559 TI - Clearance of intravitreal 3H-fluorouracil. AB - The clearance of intravitreally administered 5-fluorouracil (5-FU) was studied under five experimental conditions. The same nontoxic dose resulted in similar initial intravitreal concentrations and cleared rapidly from all eyes (approximately 90% clearance within eight hours). Half-life values ranged from 46 to 168 minutes. The longest half-life occurred in aphakic-vitrectomized eyes in which hyaluronic acid (Healon) was substituted for vitreous (168 minutes). A similar half-life was found in normal eyes (150 minutes). The shortest half-life occurred in aphakic-vitrectomized eyes postoperatively (46 minutes). Intermediate half-life values occurred in vitrectomized but phakic eyes postoperatively (67 minutes) and in aphakic-vitrectomized "quiet" eyes (at least two weeks postoperatively) (82 minutes). PMID- 4022560 TI - The significance of normal angle vessels. AB - One hundred patients (200 eyes) were examined over a one-year period for the presence of normal anterior chamber angle vessels. Normal vessels were observed in the angle in 21% of eyes examined. The types, location, and number of normal vessels are documented. The significance of these vessels in two eyes with anterior chamber angle fixated lenses is discussed. PMID- 4022561 TI - My method of extracapsular cataract extraction with implantation of a posterior chamber intraocular lens. AB - Simplified manual forms of extracapsular cataract extraction appear to be more economical, yet as safe and simple as techniques employing more complex instrumentation. The following method, employed in 40,000 cases, seems to the author to be an efficient and effective way of performing cataract extraction. One hour prior to surgery, modified retrobulbar anesthesia alone is employed using the technique described, and provides adequate akinesia as well as anesthesia. Positive pressure is applied to the eye preoperatively to assure softness of the globe at the time of surgery. An anterior capsulectomy is made with scissors, using the open-sky technique. Following the delivery of the lens nucleus and as much cortex as possible with a lens loop, the remaining cortex is removed with an angled, 23-gauge, double irrigation-aspiration cannula. Filtered balance salt solution, containing gentamycin flows into the eye through the side port (inflow) and a 3-cc syringe with 2 cc BSS for irrigation-aspiration is connected to the other (aspiration) port. A single, 25-gauge, angled irrigation cannula is used to clean up the finger cortical remains. A firm-loop intraocular lens is inserted into the capsular bag. The posterior capsule is left intact. PMID- 4022563 TI - Photo-elastic stress analysis in YAG laser surgery. PMID- 4022562 TI - Failure of pupillary dilation in early choroidal detachment. AB - Transient miosis presents a challenge in extracapsular cataract extraction and retinal detachment surgery, despite the advent of the small-pupil ophthalmoscope. Mechanisms have been proposed and preventive measures described. We describe a case of transient miosis that led to cancellation of the repair of retinal detachment and was the first sign of early choroidal detachment. PMID- 4022564 TI - A study of 200 cases of anterior chamber implants. AB - In a series of 200 eyes with Choyce or Leiske style anterior chamber implants followed for an average of 19 months, final visual acuity averaged 20/30. Eighty four percent of patients were 20/40 or better and 8% 20/100 or worse at the end of the period of observation. Cystoid macular edema occurred in 17% with most cases occurring during the first seven months. Visual loss averaged two lines and duration averaged eight months. All but one patient with adequate follow-up recovered. Cystoid macular edema appeared to be more frequent in patients who were "blinkers." The incidence of "new" glaucoma in this study was 2%. Ovalling of the pupil occurred in 46% of eyes, more frequently late than early. Early development of ovalling was more likely to be associated with imperfect implant positioning than was late. Imperfect implant position occurred in 40% of cases and inadequate early fixation resulting in propellering or rotation in 16%. Rotation was not associated with imperfect implant position. No cases of severe iritis were encountered. Pigment dispersion and vitreous herniating anterior to the optic were observed in a few eyes. No cases of corneal decompensation occurred although two eyes had minor to moderate changes. The incidence of subsequent procedures was a low 6%, helping to contribute to the high ratio of patient satisfaction. Mild tenderness and glare were the chief postoperative symptoms. PMID- 4022565 TI - Re-examining the tarsal kink syndrome: considerations of its etiology and treatment. AB - A severe corneal ulceration that is evident shortly after birth and persists in spite of adequate medical therapy, may be secondary to a congenital entropion. A vertically kinked tarsus is an unusual and frequently overlooked form of congenital entropion. Prompt recognition of this entity is essential to avoid severe corneal injury and amblyopia. We present a technique of tarsal stabilization which corrected this upper lid deformity in one case. PMID- 4022566 TI - Wills Eye Hospital Traumatic Hyphema Study. AB - Hyphema associated with nonpenetrating ocular trauma is a common cause for emergency hospitalization. The complications which result from this form of eye injury can cause permanent impairment of vision. Complications within the study population were reviewed. Analysis found a 16% rate of rebleeding, with the majority of these occurring within three to four days following the traumatic event. Unfortunately, no risk factors could be identified to help predict which patients were more at risk of complications. However, management of the complications which did develop in the study population was effective. PMID- 4022567 TI - A canthal siphon wick. AB - A simple wick can be fashioned from a cellulose surgical sponge and used to drain fluid from the ophthalmic surgical field. PMID- 4022568 TI - The early structural and functional disturbances of chronic open-angle glaucoma. Robert N. Shaffer lecture. AB - The earliest psychophysical disturbances in color vision, foveal sensitivity, spatial and temporal contrast sensitivity precede nerve fiber bundle defects of the visual field in glaucoma. Optic nervehead changes such as enlargement of the physiological cup, as well as retinal nerve fiber layer losses, also precede visual field defects. Which of these is the earliest change has not yet been recognized. Evidence for more than one mechanism of damage in glaucoma is also presented. PMID- 4022569 TI - Quantitative office perimetry. AB - This study presents a preliminary comparison of six commercially-available automated threshold static parameters, consisting of three projection perimeters (Humphrey Field Analyzer, Squid, and Octopus 500) and three light-emitting diode (LED) perimeters (Dicon 2000, Fieldmaster 50, and Digilab 350). Eighteen individuals were included in the study: 6 normal observers (31-58 years old), six patients with glaucomatous field loss in both eyes (55-70 years old), and six patients with neuro-ophthalmologic or retinal visual field abnormalities in both eyes (12-61 years old). Three aspects of quantitative testing were evaluated: (1) the patients' and normal observers' acceptance and subjective impressions of the test procedure; (2) the technician's ease of operating the device and related tasks; and (3) practitioner-oriented considerations such as test-retest reliability, comparability of test results and testing time. Our results showed that no device was clearly superior to the others in all respects. Patients were most favorably impressed with the Octopus 500, Squid, and the Fieldmaster 50, while technician impressions were most favorable to the Humphrey Field Analyzer and the Squid. The projection perimeters (Humphrey Field Analyzer, Squid, and Octopus 500) were the easiest to perform cross-comparisons of test results, although there was considerable variation in the clarity of data interpretation from one case to another. Test-retest reliability and the time of testing varied among the six automated perimeters. PMID- 4022570 TI - Is there a racial difference in physiologic cup size? AB - Although many clinicians believe that there is a racial difference in the size of the physiologic cup, this premise has not been studied. To evaluate this, we prospectively examined 100 black and 100 white volunteers. Stereoscopic optic disc photographs taken of each subject were masked to block out the fundus pigmentation, randomized, and then evaluated by an experienced clinician. The average cup/disc ratio in blacks (0.35) was significantly greater (P less than 0.0001) than that in whites (0.24) for both right and left eyes. Forty percent of the optic discs of blacks and 14% of the optic discs of whites had a cup/disc ratio greater than or equal to 0.4. PMID- 4022571 TI - Retinal nerve fiber layer photography in glaucoma. AB - Retinal nerve fiber layer (RNFL) photographs can be used for detection of early glaucomatous damage and in the follow-up of patients with established glaucoma. Enlarged black-and-white paper-prints taken with a wide-angle fundus camera as well as stereophotographs of the peripapillary retina have proven quite useful. This article gives a detailed description of both the photographic and the laboratory techniques involved in the process of making good quality RNFL photographs. PMID- 4022572 TI - Possible significance of cilioretinal arteries in open-angle glaucoma. AB - To study the possible prognostic significance of the cilioretinal artery in open angle glaucoma, the disc stereophotographs of one hundred consecutive patients with bilateral open-angle glaucoma were reviewed for the presence of cilioretinal arteries. The charts of 20 patients with unilateral cilioretinal arteries were then studied for the extent of the optic disc cupping and visual field damage. Despite the absence of a significant difference in the intraocular pressure between the two groups, eyes with cilioretinal arteries showed larger cup/disc ratios and more visual field damage when compared to the contralateral eyes without cilioretinal arteries in the same patients. PMID- 4022573 TI - Uses of fluorophotometry in glaucoma research. AB - The observation of the rate of clearance of fluorescein from the cornea and the anterior chamber by fluorophotometry permits calculation of the rate of aqueous humor flow. This technique permits studies of normal human subjects and glaucoma patients under a number of circumstances including treatment with drugs for glaucoma. A brief summary of experimental results derived from this technique is given. Simplified tables are given to assist clinicians in calculating the rate of flow of aqueous humor from fluorophotometric measurements. PMID- 4022574 TI - Early loss of central visual acuity in glaucoma. AB - Central visual acuity is usually maintained until late in the course of glaucoma. Ten patients (5 men, 5 women) between the ages of 25 and 79 were found to have decreased visual acuity associated with central or centrocaecal scotomas early in their course. Five patients had chronic open-angle glucoma, three and pigmentary glaucoma, one and juvenile glaucoma, and one had Axenfeld's syndrome. A Marcus Gunn pupil was present in all six patients not on miotics. Most lost central acuity at pressures under 30 mmHg. Seven patients had vision of 20/200 or less. All with marked visual loss had a cup disc rate of .8 or greater. Other causes were carefully ruled out. Proposed mechanisms for the development of these central defects include either double Bjerrum scotomas which extend centrally or early papillomacular bundle involvement due to temporal cupping. This study demonstrates that decreased vision with associated central field loss can be a relatively early finding in glaucoma. PMID- 4022575 TI - Change in appearance of the optic disc associated with lowering of intraocular pressure. AB - This report provides additional documentation that the appearance of the optic disc may improve after intraocular pressure is lowered in patients with glaucoma. Photographic records of one of the authors (GLS) were reviewed retrospectively. Seven previously unreported cases showing apparent improvement of the optic disc were found, and the patients' charts were reviewed. In two cases the improvement was transient, and in five it was lasting. Patients with evidence of disc improvement had an age range of 5 to 55 years. In one case, the scleral ring decreased in size following the lowering of intraocular pressure. In the other cases, the disc appeared to "fill in" without change in the size of the scleral ring. When improvement is short-lived, it presumably represents edema. When of longer duration, it may be a response to anterior repositioning of a posteriorly displaced lamina cribrosa, a decrease in diameter of the scleral ring, hypertrophy and/or proliferation of glial cells, or return towards normal of axonal metabolism. Because apparent improvement in the appearance of the optic disc can be subtle, it is usually not sought and is probably often unrecognized. Its true incidence is still unknown but appears to be underestimated. PMID- 4022576 TI - The occurrence of primary open-angle glaucoma in the fellow eye of patients with unilateral angle-cleavage glaucoma. AB - The late onset of glaucoma occurs in approximately 7% of eyes with traumatic angle cleavage. We studied 13 patients who developed glaucoma in the angle cleavage eye at an average of 34 years following trauma. Ten of the 13 patients had 270 degrees or more of angle cleavage. At the time of the initial diagnosis of angle cleavage glaucoma, there were no optic disc or visual field abnormalities in the fellow eyes. After a mean follow-up of 7.7 years, all 13 patients were reevaluated. In addition to standard examination techniques, all underwent disc photos, goniophotos, and Octopus perimetry. Seven of 13 patients (55%) had either frank glaucomatous or suspicious Octopus visual field abnormalities in the fellow eyes. Patients with angle-cleavage glaucoma appear to have at least a 50% chance of developing open-angle glaucoma in the non traumatized fellow eyes. PMID- 4022577 TI - Primary glaucoma associated with iridotrabecular dysgenesis and ectropion uveae. AB - We present nine patients with unilateral congenital ectropion uveae (hyperplasia of the iris pigment border), iris hypoplasia, characteristic gonioscopic findings, and glaucoma. A majority of these patients also demonstrated mild ptosis. In none of these patients were there any associated systemic abnormalities. The apparent ectropion uveae results from spread of the iris pigment epithelium beyond the iris ruff and onto the anterior surface of the iris. In two patients with this abnormality, histopathologic and electron microscopic findings are presented. All patients with congenital ectropion uveae should be carefully examined periodically to detect glaucoma. PMID- 4022578 TI - Acute intraocular pressure response to argon laser iridotomy. AB - Argon laser iridotomy (ALI) was performed in 50 eyes for prophylactic treatment of anatomically narrow iridocorneal angles and in 50 eyes for therapy of chronic angle-closure glaucoma. Intraocular pressure was increased 6 mmHg or more 1 to 2 hours after ALI in 19 of 50 eyes with anatomical narrow iridocorneal angles and in 23 of 50 eyes with chronic angle-closure glaucoma. Increases greater than 20 mmHg over baseline value occurred in 5 of 50 eyes with narrow iridocorneal angles and in 7 of 50 eyes with chronic angle-closure glaucoma. A clinically significant increase in intraocular pressure (defined as a pressure 30 mmHg or greater and 40% or more increased over the pre-laser value) occurred 1 to 2 hours after ALI in 11 of 50 eyes with narrow iridocorneal angles and in 17 of 50 eyes with chronic angle-closure glaucoma. There was no statistical difference (chi square P greater than 0.3) in the incidence of this complication in the two groups. Additional medical therapy was effective in lowering the acute laser-induced elevation in intraocular pressure. Patient diagnosis, patient demographics, preoperative glaucoma medication and laser treatment parameters did not predict which eyes would develop this complication. Eyes which did not have a clinically significant elevation in intraocular pressure 1 to 2 hours after ALI did not show a later increase at 24 hours. PMID- 4022579 TI - Trabeculodialysis for inflammatory glaucoma in children and young adults. AB - A modified goniotomy (trabeculodialysis) was performed on 30 eyes of 23 patients with secondary glaucoma due to chronic anterior uveitis. All but two patients also suffered from juvenile chronic arthritis (Still's disease, juvenile rheumatoid arthritis). Trabeculodialysis was unsuccessful in lowering intraocular pressure to below 21 mmHg in 12 (40%) of eyes and successful in 18 (60%) of eyes. Of the 18 successful cases, 5 required no additional medication, but in 13 cases the intraocular pressure could only be maintained at a normal level by concomitant anti-glaucoma therapy. The presence of aphakia, extent of preoperative angle closure, and patient's age had no bearing on the outcome. PMID- 4022580 TI - Neodymium: YAG laser trabeculopuncture in open-angle glaucoma. AB - Ten eyes of eight patients with open-angle glaucoma (OAG) had neodymium (Nd):YAG trabeculopuncture performed in an investigational protocol as an alternative to surgical intervention. In each, at four to six sites in the mid-trabecular meshwork, three to six superimposed applications were made (2 to 6 mJ). In four of six patients with adult OAG, a small decrease in intraocular pressure (IOP) was noted (from a mean of 25.5 to 20.0 mmHg after 3-4 weeks in the treated eyes, compared to no change at 21 mmHg in the fellow eyes). There appeared to be further attenuation of this IOP effect over the subsequent 2 to 11 months, and all patients demonstrated gonioscopic closure of all the puncture sites with time. One patient demonstrated an acute IOP elevation to 58 mmHg after the procedure, necessitating emergency filtration surgery. In contrast, in four eyes of two patients with juvenile open angle glaucoma, a dramatic lowering of IOP and improvement in tonographic outflow facility was demonstrated, although the effects were only temporary in one patient. YAG laser treatment to the trabecular meshwork may have its greatest potential usefulness when abnormalities in the uveal meshwork are involved, such as in certain cases of juvenile or congenital glaucoma, and may help identify the need for a surgical goniotomy. With more usual forms of OAG, however, widespread use of this technique should be avoided until greater efficacy can be achieved. PMID- 4022581 TI - Short- and long-term effects of postoperative corticosteroids on trabeculectomy. AB - All patients with primary open-angle or primary angle-closure glaucoma requiring trabeculectomy between January 1982 and January 1983 were entered into a randomized prospective study to evaluate the effect of postoperative corticosteroids. Twenty-three eyes in Group 1 received a cycloplegic and topical antibiotic. Twenty-nine eyes in Group 2 received the same treatment, with the addition of topical 1% prednisolone acetate. Twenty-three eyes in Group 3 received the same treatment as Group 2, with the addition of systemic prednisone. Success rate was significantly improved with the use of topical corticosteroids. Systemic steroids did not prove to be of any added benefit over topical use alone. PMID- 4022582 TI - Acute elevations of intraocular pressure following Nd:YAG laser posterior capsulotomy. AB - We performed applanation tonometry preoperatively, hourly for the first four postoperative hours and on the first postoperative day in 66 eyes after Nd:YAG laser posterior capsulotomy in order to determine the nature of the acute intraocular pressure (IOP) elevation and the risk factors involved. Forty-one percent of eyes developed an intraocular pressure greater than 30 mmHg and 14% greater than 40 mmHg. The IOP spike occurred on the second postoperative hour in 35% of eyes. Patients with controlled glaucoma prior to capsulotomy had a significantly lower mean IOP rise than patients without glaucoma. Eyes with posterior chamber IOLs were less likely to develop an IOP greater than 30 mmHg than were aphakic eyes without IOLs. There was no correlation between the laser energy or the size of the capsulotomy and the IOP rise. PMID- 4022583 TI - Ocular BB injuries. PMID- 4022584 TI - Disorders of the fundus. PMID- 4022585 TI - Treatment of myopia with atropine and bifocals. PMID- 4022586 TI - A retrospective study of nasopharyngeal carcinoma presenting over a 10-year period. AB - 67 cases of nasopharyngeal tumours presenting at the Royal National Throat, Nose and Ear Hospital over a 10-year period were examined, of which 47 were poorly differentiated carcinomas. The population under review could be subdivided into three separate groups on the basis of geographical origin: Northern European, Southern European and Middle Eastern. The proportion of poorly differentiated carcinomas in each geographical area was calculated and was found to differ significantly between the Northern European and Middle Eastern groups. PMID- 4022587 TI - Chondrometaplasia of the larynx. AB - A case of chondrometaplasia of the larynx is reported. The clinicopathological appearances are discussed with a review of the literature. The importance of distinguishing this lesion from cartilaginous tumors is emphasized. PMID- 4022588 TI - Surgical correction of subglottic stenosis in children. A follow-up study. AB - In general, subglottic stenosis in children is one of the most difficult problems to treat surgically. Six patients, aged 4-9, requiring a tracheostomy due to severe subglottic stenosis are reviewed. Decannulation was difficult to perform in these cases. All children in this series underwent surgical correction of subglottic stenosis. Patients had been successfully decannulated with no evidence of recurrent stenosis and were followed up for a period of 2-9 years. Our cases which were followed up for 2-9 years address the issue raised by opponents of surgical correction of subglottic stenosis in children, namely the consideration that the laryngeal growth potential may be adversely affected by surgery. PMID- 4022589 TI - Treatment of auricular hematoma using button technique. AB - 10 male patients suffering from auricular hematoma were treated by evacuation of the hematoma followed by suturing two buttons to the ear using through-and through staying silk sutures, leaving them attached for 1 week. Not a single case of recurrence has been encountered as this technique eliminates the dead space and does not allow reaccumulation of the hematoma. PMID- 4022590 TI - Submucosal diathermy of the inferior turbinate and the congested nose. AB - Surgical correction of the congested nose is frequently attempted. In the absence of a septal deformity, engorgement of the inferior turbinate is usually held to be the culprit, and various procedures have been advocated to counter this problem. Submucosal diathermy to the inferior turbinates is widely practised, but relatively little has been published about it. 204 patients who underwent submucosal diathermy of the inferior turbinates between 1977 and 1983 have been studied. 60 patients have been followed up by questionnaire, for periods ranging from 1 to 5 years since surgery. Surgery was of benefit in up to 72% of cases. Surgical technique and the problems of patient selection and assessment are discussed. PMID- 4022591 TI - Vestibular neuronitis: neurotological findings and progress. AB - Neurotological follow-up observations were conducted on 38 of 43 cases of vestibular neuronitis treated between 1972 and 1983. The average observation period was 1 year and 3 months (range from 1 month to 9 years and 4 months) and 17 cases were followed for more than 1 year. The tests used for evaluation in this series were the following: spontaneous nystagmus, head positional nystagmus, a caloric test and a computed galvanic body sway test (GBST) conducted by Yamaguchi University. Changes in subjective symptoms are also noted. The main subjective complaint was vertigo (whirling; 93%). The remaining subjects noticed a floating sensation and unsteadiness of gait. In 50% of the cases, vertigo subsided by the end of the 3-month period, but 6 subjects suffered from an intractable dizzy sensation for over 1 year. Even after 3 years, 3 of these 6 cases were bothered by dizzy sensations. Especially in the central lesion, these 3 subjects had no other causative disease. Spontaneous nystagmus, which was usually horizontal and direction fixed, remained in 50% of the cases after the 1 year period. All of the cases tested showed reduced caloric responses. 21 of the 38 cases showed no response in cold caloric stimulation (including ice water) at the initial test. 13 of the 21 cases were followed satisfactorily and examined twice or more by caloric testing. 5 of these 13 cases did not recover in the caloric test even after more than 1 year.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4022592 TI - Nasal mucosal blood flow in atrophic rhinitis. AB - Among many theories about the etiology of atrophic rhinitis with ozena, a reduced mucosal blood flow has been suggested, possibly caused by 'sympathetic spasm'. The nasal mucosal blood flow has been investigated in 6 patients with this disease before and after topical administration of a sympathomimetic drug. No difference in action compared to healthy subjects was found. Other pathophysiological mechanisms must be searched for. PMID- 4022593 TI - [Stressful state of the ankle joint on photoelastic models with artificial ligaments]. PMID- 4022594 TI - [Variants of osteogenesis in the treatment of flail pseudarthroses by the compression-distraction method]. PMID- 4022595 TI - [Role of blood circulation in reparative osteogenesis]. PMID- 4022596 TI - [Effect of the functional state of neurocytes of the anterior hypothalamus on reparative bone regeneration]. PMID- 4022597 TI - [Predicting the results of surgical treatment of radicular syndromes in hernias and massive protrusions of lumbar intervertebral disks]. PMID- 4022598 TI - [Clinical aspects and classification of congenital and acquired clubhand]. PMID- 4022599 TI - [Legg-Perthes disease and multiple epiphyseal dysplasia]. PMID- 4022600 TI - [Biomechanical substantiation of osteosynthesis with a cluster of pins in fractures of the tibial condyle]. PMID- 4022601 TI - [Epicondylitis of the humerus and styloiditis of the radius]. PMID- 4022602 TI - [A method of compression osteosynthesis in periarticular fractures of long tubular bones]. PMID- 4022603 TI - [A method of inserting a guide pin using a special device in osteosynthesis of fragments of the femur neck]. PMID- 4022604 TI - [A method of treatment of patients with fractures of the posterior border of the tibia using equipment for extrafocal osteosynthesis]. PMID- 4022605 TI - [A method of treatment of congenital muscular torticollis in the postoperative period]. PMID- 4022606 TI - [Results of discussion on the topic: "What is meant by primary surgical debridement of wounds?"]. PMID- 4022607 TI - [Experience with the treatment of patients with open fractures of the locomotor system with associated and multiple injuries]. PMID- 4022608 TI - [Injuries of the sacrum and coccyx in children]. PMID- 4022609 TI - [Combined fractures of the pelvic bones and the femur in children]. PMID- 4022610 TI - [Problem of the clinical manifestations of the syndrome of post-traumatic dyslipidemic coagulopathy in patients with bone injuries]. PMID- 4022611 TI - [Morphological substantiation of the selection of rational therapeutic tactics in subcutaneous ruptures of tendons of the limbs]. PMID- 4022612 TI - [The biomechanical study of osteosynthesis of the olecranon]. PMID- 4022613 TI - [Various characteristics of preoperative preparation, amputation and postoperative management of patients with occlusive diseases of the blood vessels of the extremities]. PMID- 4022614 TI - [The cybernetic approach in the prognosis of the outcome of conservative treatment of congenital hip dislocation in children]. PMID- 4022615 TI - [Role of heterolateral muscular strains in the mechanogenesis of scoliosis]. PMID- 4022616 TI - [Infrared thermography in the diagnosis of bone tumors]. PMID- 4022617 TI - [Experience with endoprosthesis of the hip joint]. PMID- 4022618 TI - [Individual approach in the study of the psychological causes of the occurrence of trauma in children for the elaboration of preventive measures]. PMID- 4022619 TI - [Osteosynthesis with metal plates in the treatment of fractures of long tubular bones]. PMID- 4022620 TI - [Classification of fractures of pelvic bones]. PMID- 4022621 TI - [Decreasing the incidence of collapse of the necrosed femur head by emergency osteosynthesis in femoral neck fractures]. PMID- 4022622 TI - [Radiologic examination of the spread of rectal tumors]. PMID- 4022623 TI - [HLA antigens and morphology of the small intestinal mucosa in Duhring's juvenile dermatitis herpetiformis]. PMID- 4022624 TI - [Successful intravenous Zovirax/acyclovir therapy in a case of adult varicella progressiva complicated by extensive bilateral pneumonia]. PMID- 4022625 TI - [Quo vadis, radiologus? The joy of riddle solving or invasive technics?]. PMID- 4022626 TI - [Questioning the interpretation of a report (Achilles tendon rupture as a symptom of hyperlipoproteinemia II)]. PMID- 4022627 TI - [Rational examination of thyroid function]. PMID- 4022628 TI - [Significance of serum theophylline levels in the management of childhood asthma]. PMID- 4022629 TI - [A case of immobile cilia syndrome]. PMID- 4022630 TI - [Confusion in the orthography of Hungarian medical terminology]. PMID- 4022631 TI - [Current views on the surgical management of the traumatic rupture of the spleen]. PMID- 4022632 TI - [The social background of people attempting suicide]. PMID- 4022633 TI - [Percutaneous catheter-embolization in carcinoid liver metastasis]. PMID- 4022634 TI - [Cancer prevention in developing countries]. PMID- 4022635 TI - [Significance of electroneurography in the diagnosis of diabetic amyotrophy]. PMID- 4022636 TI - [Tibial head osteotomy in the treatment of gonarthrosis]. PMID- 4022637 TI - [Results of tibia condyle osteotomy]. AB - The subjective and objective results of infra-condylar tibia condyle osteotomy are presented, based on a study of 71 cases. Arthroplasty of the knee joint can often be avoided by performing an infra-condylar tibia condyle osteotomy, taking into consideration the contra-indications, in cases of painful (varus) gonarthrosis becoming mainly manifest in a joint compartment, combined with an axis shift. The gait capacity can be improved, the subjective pain symptomatology be diminished and progression of the arthrosis might be avoided. The good results correlate with an optimal correction of the axis condition; in cases of varus gonarthrosis a slight overcorrection beyond the physiological valgus position of 7 degrees and in cases of valgus gonarthrosis a physiological valgus position of 7 degrees should be aimed at. PMID- 4022638 TI - [Indications, surgical technic and results of transcondylar tibia osteotomy in gonarthrosis. Experiences based on a follow-up study of 783 tibia osteotomies]. PMID- 4022639 TI - [Indication, technic and results of supra- and infracondylar osteotomy in osteoarthrosis of the knee joint]. PMID- 4022640 TI - [Influence of the patella on the equilibrium of the knee joint. Mutual effects of patellar and femorotibial arthrosis]. PMID- 4022641 TI - Do the eyes have it? PMID- 4022642 TI - Effect of imposed step-movements and pulse-movements of the retinal image on perception of hue with coloured targets. AB - There is strong experimental evidence that colour discrimination depends upon signals originating at colour boundaries. Controlled movements were imposed on a boundary between an illuminated coloured area and a dark area in a previously stabilized image. Red, yellow, green and blue fields were used. Step-movements of amplitude M min arc and pulse-movements of amplitude M min arc and pulse width tau s were studied. The movement M50 to produce 50% positive responses for perception of hue was measured as a function of retinal illuminance, boundary length and speed for step-movements and pulse-width (tau) for pulse movements. Signal/photon-noise ratios were calculated. PMID- 4022644 TI - Spatial frequency range in the detection process--1. Narrow bars. AB - The effect upon the detectability of narrow bars of ideal low-pass and high-pass filters was investigated. The results indicate that for optimum detection of the stimulus, spatial frequency components up to about 10 c/deg need to be transmitted. Two models (a multi-channel model, incorporating probability summation across spatial frequency, and a Grating Sensitivity Curve model) were used in attempting to fit the results. The multi-channel model provided a more realistic fit, but both models ultimately failed because of non-linearity in the summation of responses to frequency components. PMID- 4022643 TI - The influence of adapting velocity and luminance on the movement after-effect. AB - The response of movement-sensitive mechanisms to both velocity and luminance may be investigated by means of the movement after-effect (MAE). A high contrast (98%) drifting grating having a spatial frequency of 1c deg-1 was used with four adapting velocities of 0.90, 2.87, 4.70 and 7.55 deg sec-1 to confirm their significant effect on initial MAE velocity (F = 29.83, P less than 0.01) and duration (F = 12.36, P less than 0.01). Four mean luminance levels of 4.5, 12.6, 42.9 and 126 cd m-2, spanning 1.5 log units of illumination, demonstrate its subtle effect on both initial MAE velocity (F = 4.11, P less than 0.01) and duration (F = 3.00, P less than 0.05). It is argued that adaptation of movement sensitive mechanisms is more accurately reflected by the initial MAE velocity than its duration. The tracking technique which was employed, whilst accurate at low velocities, progressively underestimates the MAE velocity with increasing velocity. With a velocity of 1.2 deg sec-1 the under-estimate is 12%, rising to 23% at 2 deg sec-1. The tracking procedure, however, remains a reliable technique for assessing low velocity MAEs. PMID- 4022645 TI - A suprathreshold measure of perceived brightness. AB - In response to an energy flux density, E(lambda), the output of a linear detector of radiation with spectral response R(lambda) can be calculated by integrating the product R(lambda) E(lambda) over the spectral range for which R (lambda) and E (lambda) are both non-zero. This method is also applied when the eye is used as a detector of radiation although the non-linearity condition and the associated perception of colour as well as brightness make the validity of this approach difficult to assess. The quantity computed in this way when the CIE luminous efficiency function [i.e. the V(lambda) curve] is used as a measure of the spectral response of the eye is referred to as luminance and is often regarded as the objective correlate of perceived brightness. Judd (1951) showed that the use of the CIE luminous efficiency function in this way underestimates the brightness of short wavelength lights. More recently the inappropriate use of the V(lambda) function has resulted in predictions of luminance levels for light-sources which were not consistent with direct estimates of visual effectiveness (see Kinney, 1983). In this paper, the perceived brightness of coloured lights is investigated using a modified, delayed, brightness-matching technique. Psychometric response functions were obtained for some twenty coloured test targets which subtended a visual angle of 2 degrees at the observer's eye, whilst adaptation was maintained to a constant white (3900 K) field. The spectral sensitivity functions derived from these data show little variation for a number of different viewing conditions, but they are significantly different from the CIE luminous efficiency function.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4022646 TI - Rapid fading of visual sensations in a subject with a parietal-occipital tumour. AB - We present psychophysical data measured for a single subject, who had a tumour in the left parieto-occipital region, located by CT scan and post-mortem study. Her vision was characterised by rapid fading during voluntary fixation of images located in the right hemifield. We describe a number of simple tests which we developed in order to study this phenomenon. The results of these tests established that significant loss of function occurs within 1 s of fixation and that the effects associated with fixation are spatially localised. We compare our subject's response characteristics with those observed in other cases of visual disturbance and we examine the possible underlying mechanisms which give rise to the rapid fading of her visual images. PMID- 4022647 TI - The algebra of sphero-cylinders. AB - Sphero-cylinders are shown to be representable by formal vectors. An algebra applicable to sphero-cylinders is stated and mathematically consistent operations are defined. Examples of practical applications of some operations are given. PMID- 4022648 TI - A comparison of different models of extraocular muscle cooperation. AB - Different assumptions about the way in which the extraocular muscles act have been evaluated by comparing a set of models of extraocular muscle cooperation, each of which differ by just one assumption, against clinical data from patients with isolated nerve palsies. PMID- 4022649 TI - The effect of illumination and foveal fusion lock on clinical fixation disparity measurements with the Sheedy Disparometer. AB - The Sheedy Disparometer is a clinical instrument designed to measure fixation disparity and hence determine forced vergence--fixation disparity curves. The target design includes a central 1.5 degrees fusion-free area. The effect of introducing a central fixation target to the instrument is investigated along with the influence of ambient illumination level on fixation disparity. All curve parameters, i.e. curve type, slope, X- and Y-intercepts were found to significantly alter with the introduction of a foveal lock. Illumination changes did not cause significant differences in any parameter. PMID- 4022650 TI - The Arden gratings in optometric practice. AB - The use of the Arden gratings (AO contrast sensitivity system) in optometric practice is evaluated. A total of 320 patients presenting for eye examination were screened with the gratings. Sixty-four eyes (10%) gave abnormal grating scores although results from conventional examination techniques revealed no abnormality. Of the 110 abnormal eyes detected by routine examination techniques, 8 presented with normal grating scores, 6 with "borderline suspect" scores and 96 with abnormal scores. Used in isolation, the failure rate of the Arden gratings to detect ocular abnormality in the patient population was 1.3% and the "false positive" referral rate was 10%. PMID- 4022651 TI - Inter-relationships between British drivers' visual abilities, age and road accident histories. AB - Statistical analysis is described of data on 1000 British drivers' accident histories and their performance on a vision screening instrument. Significant positive associations are evident between various accident variables and tests of hyperphoria, right eye visual acuity, left eye acuity and binocular acuity. The clustering of associations is strongest for older drivers. The significance of hyperphoria has received little attention previously. The age-related associations with accidents parallel the decline with age of other visual abilities. Statutory re-testing of drivers' vision at about the age of 50 is recommended. PMID- 4022652 TI - Visual standards for driving. AB - The visual standards for drivers set by a selection of countries across the world are reviewed. It is found that there is little unanimity in what constitutes an "adequate" standard of vision for drivers of either private or public vehicles, or in the testing procedures employed. PMID- 4022653 TI - Effect of instruction and higher level control on the accommodative response spatial frequency profile. AB - Although the spatial frequency dependence of accommodation is well established, characteristics of the accommodative response profile may vary significantly, thus supporting opposing theories of accommodation control. We demonstrate the pronounced influence of instruction and higher level control on such accommodation profiles. The results suggest that extreme care be taken in the methodological considerations of such experiments, as well as the need for additional systematic investigation of these factors in accommodation studies. PMID- 4022654 TI - On reaction time histograms. PMID- 4022655 TI - Abstracts of papers presented at the meeting of the Society for Experimental Optometry. Aston, England, 23-24 July 1984. PMID- 4022656 TI - [Our experiences with the microsurgical treatment of cholesteatomas of the middle ear]. PMID- 4022657 TI - [Our observations on the effect of mechanical injuries on the activation of the otospongiosis process]. PMID- 4022658 TI - [Lop ears]. PMID- 4022659 TI - [Caloric tests in nystagmus induced in the simple optimal position and reversed optimal position]. PMID- 4022660 TI - [Our experiences with the evaluation of occupational diseases of the organ of voice]. PMID- 4022661 TI - [Study of hearing in increased atmospheric pressure]. PMID- 4022662 TI - [Importance of cooperation between the laryngologist and pathologist-oncologist in the prevention, development and treatment of cancer of the vocal cords]. PMID- 4022663 TI - [Management of hemangiomas of the parotid gland in children]. PMID- 4022664 TI - Clinical problem solving: learned process. PMID- 4022665 TI - Changes in medicine cause ethical problems. PMID- 4022666 TI - Biliary atresia. PMID- 4022667 TI - Management of Reye's syndrome: need for early diagnosis and intravenous treatment of stage I non-comatose cases. AB - Clinicians and nurses should obtain a history of antecedent illness occurring within 2 weeks of the onset of vomiting. Ninety percent of school-age children will give a history of an antecedent illness (varicella or influenza-like respiratory illness) within 1 week of the onset of vomiting. The vomiting of Reye's syndrome is usually persistent, lasting for 24 to 96 hours before the onset of serious brain signs. We believe that any child with the history of flu or chickenpox within 1 week of the onset of vomiting, which lasts for more than 12 hours, and is unusually severe or is associated with lethargy, should have an SGPT (alanine aminotransferase). This laboratory measure is clearly elevated in most cases of Reye's syndrome. PMID- 4022668 TI - Special laboratory examinations for parasitic infections. AB - Besides the routine procedures used for the diagnosis of parasites, there are a number of other diagnostic techniques available for the recovery and identification of parasites. Most laboratories do not routinely offer all of these techniques, but many are relatively simple and inexpensive to perform. This article discusses these techniques and their clinical relevance. PMID- 4022670 TI - Symposium on parasitic infections. PMID- 4022669 TI - Treatment of parasitic infections. AB - This article provides an extensive table of drugs and dosages for treatment of parasitic infections, listing the treatment regimen most commonly used. This is followed by a list of the recommended drugs, their preparations, toxicity, contraindications, and precautions. PMID- 4022671 TI - Renal metabolism in fetal and newborn sheep. AB - The substrate and oxygen uptake by some organs in intact developing animals has been described, however, the kidney has not been studied. To examine substrate and oxygen uptake by the kidney, we implanted polyvinyl catheters into the renal vein, descending aorta, inferior vena cava, and urinary bladder of 11 fetal sheep (120-125 days gestation) and eight newborn lambs (1 day postnatal). Four days after surgery, blood samples were obtained simultaneously from the renal vein, aorta, and inferior vena cava for determination of oxygen content and saturation, and glucose and lactate concentrations. Renal blood flow was determined by the radionuclide-labeled microsphere method in the fetal lambs and by measuring 14C inulin clearance in the newborn lambs. The fetal and newborn kidneys consumed oxygen at rates of 123 +/- 16 and 785 +/- 79 mumol/min/100 g kidney weight (mean +/- SEM), respectively. The increase in oxygen consumption from the fetal to the newborn period was accompanied by an increase in oxygen extraction from 25-35%, a large increase in oxygen delivery from 418 +/- 38 to 2231 +/- 127 mumol/min/100 g, and marked increases in glomerular filtration rate and sodium reabsorption (measured in six additional fetal sheep and the eight newborn lambs). This suggests that the postnatal increase in renal tubular activity is associated with an increase in oxygen consumption. Lactate was taken up by both fetal and newborn kidneys, and in nine of the 11 fetuses and in four of the eight newborns, there was net glucose release from the kidney. PMID- 4022672 TI - Long-chain acyl coenzyme A dehydrogenase deficiency: an inherited cause of nonketotic hypoglycemia. AB - Three children from unrelated families presented in early childhood with hypoglycemia and cardiorespiratory arrests associated with fasting. Significant hepatomegaly, cardiomegaly, and hypotonia were present at the time of initial presentation. Ketones were not present in the urine at the time of hypoglycemia in any patient; however, dicarboxylic aciduria was documented in one patient at the time of the acute episode and in two patients during fasting studies. Total plasma carnitine concentration was low with an increased esterified carnitine fraction. These findings suggested a defect in mitochondrial fatty acid oxidation, and specific assays were performed for the acyl coenzyme A (CoA) dehydrogenases. These analyses showed that the activity of the long-chain acyl CoA dehydrogenase was less than 10% of control values in fibroblasts, leukocytes, and liver tissue. Activities of the medium-chain, short-chain, and isovaleryl CoA dehydrogenases were not different from control values. With cultured fibroblasts, CO2 evolution from long-chain fatty acids was significantly reduced, while CO2 evolution from medium-chain and short-chain fatty acids was comparable to control values--findings consistent with a defect early in the beta-oxidation sequence. Studies of acyl CoA dehydrogenase activities in fibroblasts and leukocytes from parents of the patients showed levels of long-chain acyl CoA dehydrogenase activity intermediate between affected and control values and indicated an autosomal recessive form of inheritance of this enzymatic defect.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4022673 TI - Genetic deficiency of medium-chain acyl coenzyme A dehydrogenase: studies in cultured skin fibroblasts and peripheral mononuclear leukocytes. AB - Medium-chain acyl coenzyme A (CoA) dehydrogenase deficiency was demonstrated in fibroblasts and/or mononuclear leukocytes from 14 patients, most of whom initially presented early in childhood with a Reye-like syndrome associated with hypoketotic hypoglycemia, dicarboxylic aciduria, and low levels of plasma carnitine. Parents of these patients had intermediate levels of medium-chain acyl CoA dehydrogenase activity, consistent with their being heterozygous for an autosomal recessive trait. All patients had normal levels of long-chain acyl CoA dehydrogenase activity, but had reduced short-chain acyl CoA dehydrogenase activity. Fatty acid oxidation was examined in cultured fibroblasts from five of the patients, using a series of 14C-labeled fatty acids of different chain length (palmitic, octanoic, and butyric). Oxidation of [1-14C]-octanoic acid was less than 20% of control levels: [1-14C], [6-14C]-, [16(14)C]-, and [14C(U)]-palmitic acid oxidation rates were 88, 51, 13, and 42% of control rates, respectively. [1 14C]-butyric acid was oxidized normally. These data extend our previous findings of medium-chain acyl CoA dehydrogenase deficiency in liver tissue from three of these patients. They demonstrate the value of cultured fibroblasts and leukocytes in the diagnosis and evaluation of inherited disorders of fatty acid oxidation. PMID- 4022674 TI - Aldosterone metabolism and transepithelial potential difference in normal and cystic fibrosis subjects. AB - The transepithelial potential difference (PD) is raised across cystic fibrosis (CF) respiratory epithelia. This raised voltage reflects active sodium absorption across a relatively chloride impermeable membrane. Because relatively little is known about the regulation of the rate of sodium absorption across mammalian airways, we assessed the possible contribution of aldosterone to the PD in normal and CF respiratory epithelia. Aldosterone excretion in five CF patients was 12.2 +/- 0.9 micrograms/24 h, a mean value not different from normal control subjects (13.6 +/- 1.5 micrograms/24 h, n = 5). Despite similar aldosterone excretion rates, nasal PD was more than 2-fold greater in the CF patients (-53.6 +/- 6.4 mV) than normal subjects (-21.3 +/- 1.4 mV). The effect of an aldosterone antagonist, spironolactone, on aldosterone excretion and nasal and rectal PD was evaluated in four CF patients and five normal subjects. During spironolactone administration, aldosterone excretion increased (2- to 4-fold) and rectal PD decreased in both groups. However, nasal PD was unchanged in each group (CF = 52.1 +/- 4.3 mV pre, -53.6 +/- 1.4 mV during; normal = -21.2 +/- 3.1 mV pre, 21.6 +/- 3.2 mV during). We conclude that neither increased aldosterone secretion rates nor organ sensitivity to aldosterone can account for the abnormally raised PD that characterizes the respiratory epithelium of subjects with CF. PMID- 4022675 TI - Whole body protein synthesis and energy expenditure in very low birth weight infants. AB - The aim of the present work was to study whole body protein synthesis and breakdown, as well as energy metabolism, in very low birth weight premature infants (less than 1500 g) during their rapid growth phase. Ten very low birth weight infants were studied during their first and second months of life. They received a mean energy intake of 114 kcal/kg X day and 3 g protein/kg X day as breast milk or milk formula. The average weight gain was 15 g/kg X day. The apparent energy digestibility was 88%, i.e. 99 kcal/kg X day. Their resting postprandial energy expenditure was 58 kcal/kg X day, indicating that 41 kcal/kg X day was retained. The apparent protein digestibility was 89%, i.e. 2.65 g/kg X day. Their rate of protein oxidation was 0.88 g/kg X day so that protein retention was 1.76 g/kg X day. There was a linear relationship between N retention and N intake (r = 0.78, p less than 0.001). The slope of the regression line indicates a net efficiency of N utilization of 67%. Estimates of body composition from the energy balance, coupled with N balance method, showed that 25% of the gain was fat and 75% was lean tissue. Whole body protein synthesis and breakdown were determined using repeated oral administration of 15N glycine for 60-72 h, and 15N enrichment in urinary urea was measured. Protein synthesis averaged 11.2 g/kg X day and protein breakdown 9.4 g/kg X day. Muscular protein breakdown, as estimated by 3-methylhistidine excretion, contributed to 12% of the total protein breakdown.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4022676 TI - The development of antioxidant enzymatic defense in the perinatal rat lung: activities of superoxide dismutase, glutathione peroxidase, and catalase. AB - This report describes the development of superoxide dismutase, glutathione peroxidase, and catalase activities in fetal (days 16-22) and neonatal (day 2 postpartum) lungs of normal rats. Each of the enzymes showed an individual pattern of development in the perinatal period. Glutathione peroxidase activity increased by 135% (p less than 0.001) during the last 3 days before birth, catalase activity by 105% (p less than 0.01) during the first 2 postnatal days, and the activity of superoxide dismutase by 52% (p less than 0.05) from gestational day 19 to 2 days after birth. Contamination by superoxide dismutase from blood in the lung samples accounted for less than 2% of the activity. In contrast, not less than 10-30% of glutathione peroxidase and catalase originated from the blood; and corrections were made for this source of error in each sample. PMID- 4022677 TI - Prostaglandin production and zinc depletion in human pregnancy. AB - An association between zinc depletion and intrauterine growth retardation might occur through disturbed prostaglandin (PG) synthesis. The zinc content and PG metabolism of leucocytes from control, nonpregnant women and mothers 24-48 h after delivery, were measured and related to fetal growth and maternal smoking. Mothers of small for gestational age babies had lower polymorphonuclear and mononuclear cell zinc contents than mothers of appropriate for gestational age babies or nonpregnant controls. Monocytes were the major leucocytes producing PGs. Mothers of small for gestational age babies had higher PGE2:F2 alpha ratios than mothers of appropriate for gestational age babies. PGF2 alpha production and PGE2:F2 alpha ratio were correlated with tissue zinc status. Monocytes from nonsmokers tended to produce more PGs than those from smokers but the differences were not significant. Mild maternal zinc depletion is not significantly sufficient to alter absolute PG production, but is associated with altered differential production of PGs in human leucocytes. Zinc depletion or malnutrition may contribute to intrauterine growth retardation by affecting placental and/or umbilical PG production. PMID- 4022678 TI - The chronically reserpinized rat as a model for cystic fibrosis: abnormal Cl- transport as the basis for reduced salivary fluid secretion. AB - Saliva secretion induced by 10(-6) M acetylcholine was reduced 74% in isolated, perfused submandibular glands of control rats when the gland was perfused with solutions containing either furosemide (10(-3) M) or sulfate (instead of chloride) as the major anion. In regular (Cl-containing) perfusates without furosemide, saliva secretion was reduced 74% in isolated glands of rats treated with seven intraperitoneal doses of reserpine (0.5 mg/kg body weight). In the latter, addition of furosemide or replacement of perfusate Cl- with SO = 4 caused a further 35% drop in saliva volumes. Salivary Cl- concentrations were lower in saliva from the treated animals and were reduced further by furosemide, which also reduced the Cl- concentrations of control saliva. In submandibular acini isolated from control glands, acute exposure to 36Cl (1 mu Ci/ml) resulted in a rapid uptake of tracer so that a constant content of isotope (approximately 9.5 nM/mg protein) was attained in 4-5 min and maintained for 30 min. This basal uptake reached 8.4 nM/mg protein in acini isolated from glands of reserpine treated rats and attainment of a steady state of tracer content was delayed and required 8-10 min. Exposure to acetylcholine reduced uptake and steady state tracer content by 35% in control acini, but had no effect in acini of reserpine treated rats. Acetylcholine caused a rapid decrease (42% in 1 min) in 36Cl content of control acini which were preloaded with tracer for 12 min, but only a 23% decrease in acini of reserpine-treated rats.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4022679 TI - The effect of short-term starvation on mucosal barrier function in the newborn rabbit. AB - The compromised human newborn frequently presents with overwhelming feeding problems which lead to inadequate intake. These problems may affect the development of the small intestine, especially mucosal barrier function, leading to increased infections and susceptibility to allergens. To study this, an animal model was established using neonatal rabbits deprived of nutrients from birth until 72 h. Mucosal barrier function was compared in deprived and control (naturally fed 72-h-old animals) rabbits by measuring immunoreactive bovine serum albumin in serum 4 h after intragastric infusion of crystalline bovine serum albumin (200 mg/100 g body weight). Trypsin activity was measured in rinse fluid obtained from the small intestine. Representative sections of jejunum from control and experimental animals were formalin fixed and stained with hematoxylin and eosin for morphologic comparison. Following the bovine serum albumin feeding, a significantly increased serum immunoreactive bovine serum albumin and significantly decreased trypsin-like activity of the small intestinal rinse fluid was noted in starved animals compared to controls. In addition, the enterocytes of malnourished animals were more cuboidal and contained fewer and smaller supranuclear granules on microscopic examination than the enterocytes of controls. This study suggests that short-term starvation in newborns affects mucosal barrier function. Acute starvation may place newborns at increased risk for infections and allergic disease. PMID- 4022680 TI - [Cystinuria in children]. PMID- 4022681 TI - [Surgical treatment of vesico-ureteral reflux in infants]. PMID- 4022682 TI - [Hospital infections of the urinary tract in infants]. PMID- 4022683 TI - [Clinico-morphological analysis of congenital nephrotic syndrome]. PMID- 4022684 TI - [Arterial hypertension in schoolchildren--incidence and causes]. PMID- 4022685 TI - [Interstitial nephritis with iritis]. PMID- 4022686 TI - Prevention of preterm births: a perinatal study in Haguenau, France. AB - A reduction in preterm births has been observed in Haguenau (Eastern France) during a 12-year intervention study with a program for prevention of preterm deliveries. The Perinatal Study of Haguenau was an observation tool used in a stable population, and it allowed measurement of the way women have progressively responded to the new proposals in prenatal care. It also allowed measurement of the results of the interventions: low birth weight (less than 2,500 g) and preterm birth rates (less than 37 weeks of gestation) among single live births. The total duration of the study was divided into three periods of four years (1971 through 1974, 1975 through 1978, and 1979 through 1982), for which the numbers of single live births are 5,763, 4,957, and 5,919, respectively. For the same periods, the low-birth-weight rates, 4.6%, 4.0%, and 3.8%, respectively, showed a significant decrease (P less than .001). Following a similar pattern, the rates of preterm birth were 5.4%, 4.1%, and 3.7% (a significant reduction with P less than .001). These improvements in pregnancy outcome do not disappear after standardization of mother's age, high blood pressure, or social class distribution. These findings, which concur with the results of others, enhance the hypothesis of a direct relationship between a prevention program and a reduction in preterm birth rates. PMID- 4022687 TI - Oral rehydration therapy for acute diarrhea in ambulatory children in the United States: a double-blind comparison of four different solutions. AB - Oral rehydration solutions containing 50 to 90 mmol/L of sodium have recently been recommended for the treatment of diarrhea in both hospitalized and ambulatory children in the United States. Few data are available, however, from ambulatory US children. Therefore, we conducted a randomized double-blind study comparing the use of four different oral rehydration solutions with differing concentrations of sodium, glucose, and base. Ambulatory children less than 2 years of age with acute diarrhea (N = 140) were randomly chosen to receive solutions containing sodium at 90 (solution A), 50 (solution B), and 30 mmol/L (solutions C and D). All oral rehydration solutions contained 20 g/L of glucose except solution D which contained 50 g/L of glucose. Solution A contained bicarbonate as its base source whereas the other three contained citrate. All but three (98%) children were treated uneventfully according to the study protocol, and there were no differences among groups in measurements of clinical outcome. It was concluded that in ambulatory US children, oral rehydration solutions containing 90, 50, or 30 mmol/L of sodium can be used safely for the treatment of mild acute diarrhea and that citrate is as efficacious as bicarbonate in the correction of acidosis. PMID- 4022688 TI - Predictive value of abnormal physical examination findings in ill-appearing and well-appearing febrile children. AB - In order to study the occurrence and positive predictive value of history and physical examination findings suggestive of serious illness in ill-appearing and well-appearing febrile children, 103 consecutive children aged less than or equal to 24 months with fever greater than or equal to 38.3 degrees C were evaluated from July 1, 1982 to Nov 24, 1982. Patients were initially classified by an attending physician (A) as to whether they appeared ill (Yale Observation Scale score greater than 10) or well (scale score less than or equal to 10). The history was then taken by two attending physicians (A and B) and a resident; the physical examination was performed by attending physician B and the same resident. As history and physical examination findings were elicited, they were scored as to whether they did or did not suggest a serious illness. Serious illness was defined as the presence of a positive laboratory test. Ill-appearing patients had a significantly greater (P less than .001, Fisher's exact test) occurrence of physical examination findings suggesting serious illness (14 of 22, 64%) than well-appearing children (12 of 81, 15%). The positive predictive values of abnormal physical examination findings for serious illness in ill-appearing (11 of 14, 79%) and well-appearing children (3 of 12, 25%) were significantly different (P = .02 by Fisher's exact test). The trends for abnormal history findings in ill-appearing and well-appearing children were similar to those for abnormal physical examination findings but did not achieve statistical significance. The results, indicating an important interaction between a febrile child's appearance and physical examination findings, are discussed in terms of probability reasoning in clinical decision making. PMID- 4022689 TI - Medical management of congenital nasolacrimal duct obstruction. AB - A consecutive series of 113 infants seen with congenital nasolacrimal duct obstruction were treated with local massage and topical antibiotic ointment. In 107 of the infants the obstruction was resolved within 8 months of initiation of this form of management. Nearly all of the infants were spared a surgical procedure that probably would have been performed if early probing of the nasolacrimal system had been advocated. PMID- 4022690 TI - Ten years of experience with 1,000 hyperactive children in a private practice. AB - A summary of the author's experience with 1,000 hyperactive children treated in a private practice over a period of 10 years is presented. Of 1,000 children entering the office, 872 were treated with stimulants for more than 6 months. Of these 872 children, 137 (16%) were considered as treatment failures; 735 (84%) had a positive response to medication. A follow-up of 197 patients in "remission," after treatment, suggested that symptoms had reappeared in 20% of the cases. The length of treatment in a group of 494 children still under observation on Dec 31, 1981, indicated that the majority of boys were treated for between 3 to 5 years; girls were treated for 2 to 3 years. Approximately 10% of the children received medication for 1 to 2 years, whereas about 20% were treated for more than 6 years. It was concluded that treatment with a stimulant for 5 to 10 years is a safe and efficient way to help hyperactive children during a difficult time of life. PMID- 4022691 TI - Fifteen-year follow-up of a behavioral history of attention deficit disorder. AB - A 15-year longitudinal study of 369 children originally classified in second grade as exhibiting or not exhibiting behaviors commonly associated with attention deficit disorder was made. Diagnostic data were collected on these children in second, fourth, and fifth grades and subsequent school performance was evaluated after ninth and twelfth grades. Interviews were conducted 3 years after their graduation from high school. The ninth and twelfth grade records reveal that those who had previously been identified as showing behavior related to attention deficit disorder later performed significantly more poorly in school and had poorer social adjustment. Interviews in early adulthood continued to reveal differences in outcome between normal subjects and those earlier classified as having attention deficit disorder. Many of these differences could not be directly attributed to poor academic performance. A subgroup of students who were rated favorably by their elementary school teachers were found to perform better during high school than other members of the normal group in academic areas, but they generally did not differ from normal subjects in nonacademic areas. PMID- 4022692 TI - Alcohol and unnatural deaths in San Francisco youths. AB - Alcohol has been shown to play an important role in youthful unnatural deaths in one California county; its contribution was not limited to motor-vehicle fatalities. In contrast to existing approaches, several new prevention strategies imply that limiting the availability and consumption of alcohol may result in a reduction of the full range of alcohol-related injuries. PMID- 4022693 TI - Reye syndrome associated with aspirin therapy for systemic lupus erythematosus. AB - A 14-year-old girl in whom Reye syndrome developed during aspirin therapy for an inflammatory disorder proven to be systemic lupus erythematosus is reported. This case and similar cases of Reye syndrome in patients with juvenile rheumatoid arthritis suggest that an etiologic relationship exists between salicylate therapy and Reye syndrome in children with collagen vascular disorders. PMID- 4022694 TI - Primary lymphedema in children and adolescents: a follow-up study and review. AB - Primary lymphedema, a disorder causing persistent swelling in an extremity, is rare in children and adolescents; it affects 1.15/100,000 persons less than age 20 years. It primarily affects girls near menarche. The records of 125 children and adolescents, aged 0 to 20 years, who were examined at the Mayo Clinic were analyzed; 99 of these patients were contacted to obtain follow-up data. The influences of estrogen and inflammation are thought to be important etiologic factors in primary lymphedema. The diagnosis can be made on the basis of a thorough history and physical examination. Lymphangiograms, venograms, and biopsies add nothing to the diagnosis because of the low incidence of tumor in children and adolescents. Conservative treatment is recommended: a Jobst-type stocking, elevation, and proper foot care. Diuretics are not recommended. Careful psychologic counseling, especially in adolescents, is highly recommended. PMID- 4022695 TI - Predicting mortality in low-birth-weight infants with pulmonary interstitial emphysema. AB - Due to the high mortality associated with pulmonary interstitial emphysema in the low-birth-weight infant, a method was developed to predict the infants most at risk for death. This information will allow the discriminant selection of patients for future trials of an alternative method of mechanical ventilation, high-frequency ventilation. During a 3-year-period (July 1, 1979 through June 30, 1982), 70 infants were retrospectively analyzed to determine the clinical parameters important in predicting mortality. The infants at highest risk for death included those of younger gestational age, those with birth weight less than 1,500 g (95% of all mortalities), and those that developed pulmonary interstitial emphysema within the first 24 hours of life. Mortality sharply increased in the infants with birth weight less than 1,500 g whose ventilatory requirements exceeded a peak inspiratory pressure of 25 cm H2O on day 1. Morbidity was high in the survivors as evidenced by a 54% incidence of bronchopulmonary dysplasia. With multivariant analysis, it was possible to isolate the variables (birth weight and highest peak inspiratory pressure on day 1) most influential in predicting mortality and to construct a formula for predicting mortality in the infants with birth weight less than 1,500 g. With a subsequent prospective study of 30 infants, the predictive accuracy of the formula was established. PMID- 4022696 TI - Gastrointestinal injury in polycythemic term infants. AB - Necrotizing enterocolitis is uncommon among term infants. In this group, necrotizing enterocolitis has been associated with two risk factors: polycythemia and umbilical catheterization. During a randomized trial of partial plasma exchange transfusion for treatment of polycythemia, an increased risk of gastrointestinal problems was noted. Eight hyperviscous patients treated with partial plasma exchange transfusion, no symptomatically treated patients, and no control infants developed typical necrotizing enterocolitis (blood in the stools, pneumatosis, and systemic signs). The incidence of necrotizing enterocolitis was significantly greater among patients treated with exchange transfusion compared with patients treated symptomatically or control subjects (P less than .001). PMID- 4022697 TI - Decreased specific airway conductance in infant apnea. AB - A disorder of respiratory control is the suspected etiology in a majority of infants with apnea. Although neurologic control of breathing has been evaluated in infants surviving an apneic episode, pulmonary mechanics have not been previously measured. Pulmonary mechanics were measured during sleep in ten infants with apnea, aged 45.4 +/- 1.4 (SE) weeks postconception, and 13 control infants, aged 42.0 +/- 0.8 weeks postconception. Infant apnea patients were defined as those having at least one episode of cyanosis, limpness, and apnea requiring vigorous stimulation or resuscitation to restore normal breathing, and in whom no treatable etiology could be found. Thoracic gas volume, airway resistance, and specific airway conductance were measured in an infant body pressure plethysmograph during quiet breathing. Dynamic pulmonary compliance was measured in six infants using an esophageal balloon. Specific airway conductance was decreased in infants with apnea compared with control infants (P less than .05). Thoracic gas volume, airway resistance, and dynamic pulmonary compliance values were comparable with those of control infants. These data suggest that airway narrowing or abnormal control of airway tone during sleep may contribute to apnea in some infants. PMID- 4022698 TI - Near-miss sudden infant death syndrome in eight infants with sleep apnea-related cardiac arrhythmias. AB - Eight full-term infants between 3 and 8 weeks of age, who had had 24 to 48 hours of vague problems involving a congested upper airway and/or irritability, had a life-threatening respiratory episode at home, called a near-miss for sudden infant death syndrome event. Polygraphically monitored mixed apneas occurred in clusters during non-rapid eye movement (NREM) sleep with significant cardiac arrhythmias, predominantly sinus arrest. The cardiorespiratory problems continued during sleep in the following 8 to 12 weeks but did not recur after that time, and there were no long-term sequelae when the children were studied again 4 to 7 years later. PMID- 4022699 TI - Complications resulting from use of arterial catheters: retrograde flow and rapid elevation in blood pressure. AB - Arterial catheters, routinely used in neonatal intensive care units, have been associated with serious complications. In the present studies, retrograde blood flow occurring during routine flushing of peripheral and umbilical catheters is described. This retrograde flow is associated with a significant elevation of blood pressure at distant sites. These phenomena depend on the volume flushed and on the velocity of the flushing process. These phenomena can be prevented by flushing a small volume of 0.5 mL for a period of five seconds. PMID- 4022700 TI - Rhabdomyolysis and myoglobinemia in neonates. AB - Serial myoglobin determinations were made in 20 neonates during the first week of life to determine whether birth asphyxia results in ischemic damage to muscle with the subsequent pathologic release of myoglobin. Serum myoglobin values were significantly elevated in asphyxiated infants compared with control infants. High myoglobin values correlated with a longer duration of oliguria in the neonatal intensive care unit population. The value of urine dipstick testing for myoglobinuria screening was also evaluated. Infants with elevated myoglobin values were more likely to have a strongly positive urine dipstick for occult blood in the first 48 hours of life. These data suggest that ischemic damage to muscle with pathologic release of myoglobin occurs in the neonatal period and that urine dipstick testing provides a reasonable screening examination for myoglobinuria. PMID- 4022701 TI - Aseptic meningitis secondary to metrizamide lumbar myelography in a 4 1/2-month old infant. AB - Although metrizamide has been used as a contrast agent for myelography for the past decade, there are few reports of its use in the pediatric population. Aseptic meningitis has rarely been reported as an adverse effect of metrizamide in adults. The first pediatric case of aseptic meningitis following lumbar myelography with metrizamide is reported. PMID- 4022702 TI - Role of soy-based, lactose-free formula during treatment of acute diarrhea. AB - A controlled study was conducted comparing the standard method of treating hospitalized infants with acute diarrhea (limited starvation) with the initiation of "early feeding" using a soy-based, lactose-free formula in infants of an American Indian tribe 12 months of age or younger. Forty-three patients, randomly assigned to group A, were given a soy-based, lactose-free formula four hours after hospitalization, and 44 patients, randomly assigned to group B, received standard therapy (food was withheld for the first 48 hours of hospitalization). After the first 48 hours, the same soy-based, lactose-free formula was given to the group B patients. Fluid intake and output of stool, urine, and vomitus were measured until the diarrhea resolved. Overall, group A patients showed less mean stool output (121 +/- 129 (SD) mL/kg) than group B patients (299 +/- 319 mL/kg) (P less than .001). Furthermore, the duration of illness was significantly shorter in group A patients (54 +/- 28 hours v 93 +/- 56 hours) (P less than .001). It was concluded that soy-based, lactose-free formulas can be safely used during the acute phase of diarrheal illness in infants and that their use shortens the duration of illness and decreases stool output in comparison with standard therapy. PMID- 4022703 TI - Meningomyelocele and Hirschprung disease: theoretical and clinical significance. PMID- 4022705 TI - Pediatric generalists in an academic setting. PMID- 4022704 TI - Childhood appendicitis: factors associated with perforation. AB - A retrospective study was performed to identify factors associated with perforation in 150 children with acute appendicitis. The children's parents were interviewed about the nature and timing of care, family history of appendicitis, and history of abdominal pain episodes, and the children's medical records were reviewed. Delay in treatment--the interval between first recognized symptoms of abdominal pain and surgery--was most predictive of perforation. A treatment delay of more than 36 hours was associated with a 65% or greater incidence of perforation. Mean delay for the group with perforation of the appendix was 66.7 hours compared with 35.8 hours for the group having appendicitis without perforation (P less than .01). Mean professional delay was significantly longer in the group with perforated appendicitis than in the group having appendicitis without perforation (P less than .01), but mean parental delay was not. Children aged 1 to 4 years and those aged 5 to 8 years had a 74% and 66% incidence of perforation, respectively, compared with a 30% to 42% incidence in older children (P less than .01). Age had a significant effect upon perforation even when adjusted for delay in treatment. Other factors associated with perforation were family history of appendicitis, social class, advice given by the first health professional contacted, and the presence of fecaliths. When all factors were considered simultaneously by using logistic regression techniques, delay in treatment, age, and absence of a family history of appendicitis were all significant predictors of perforation. PMID- 4022706 TI - In search of wonder and wisdom: pediatrics in transition. PMID- 4022707 TI - Prevention of prematurity: can we do it in America? PMID- 4022708 TI - Maternal phenylketonuria. Committee on Genetics. PMID- 4022709 TI - Guidelines for the elective use of conscious sedation, deep sedation, and general anesthesia in pediatric patients. Committee on Drugs. Section on anesthesiology. PMID- 4022710 TI - Need for increased biostatistical consultation. PMID- 4022712 TI - Effectiveness of moped legislation. PMID- 4022711 TI - Protein-fortified milk in premature infants. PMID- 4022713 TI - [Plasma 25-OH D deficiency in Maghrebian children more than 10 years of age immigrated to France]. AB - From 1984 Feb 1st to April 30, 63 blood samples were collected from children more than 10 years old in the pediatric unit of CHR de St-Etienne, and analysed for 25 OH D, calcium, phosphate, magnesium and alkaline phosphatase serum concentrations. Mean 25 OH D is lower (22,6 nmol/1) in 26 migrant children (24 from Maghreb and 2 from Turkey) than in 37 European children (mean = 48,6 nmol/1; p less than 0,001). Serum concentration is under 10 nmol/1 in 3 of the 37 Europeans (8%), versus 13 of the 26 Maghrebians (50%). Mean alkaline phosphatase and phosphate are significantly higher in the 36 boys than in the 27 girls. A significative positive correlation is found between alkaline phosphatase and phosphate (r = 0,535; p less than 0,01). There is no relation between age, month of assessment, sex, height, weight, place of late holidays and any of the measured serum values. PMID- 4022714 TI - [Course of serum levels of free thyroid hormones in children from 10 days to 2 years of age]. AB - We have been studying a population of 95 normal children aged 10 days to 2 years, in order to determine the normal values of free thyroid hormone in this class of age. The concentrations were measured by radioimmunoassay (Lepetit system). Free T3 (FT3) appears remarkably stable, with a mean at 4,92 pg/ml (3,23 - 7,50 mg/ml at +/- 2SD). These concentrations are significantly higher than those of adult. Free T4 (FT4) shows a significant decrease over the first month of life, with a mean at 14,31 pg/ml (10,27 - 19,94 pg/ml at +/- 2SD). There is no significant variation between the age of one month and 2 years. The mean is 10,51 pg/ml (7,00 - 15,79 pg/ml +/- 2SD). PMID- 4022715 TI - [Neonatal primary hyperparathyroidism caused by clear cell hyperplasia]. AB - Neonatal primary hyperparathyroidism is rare but must be evoke during respiratory distress with thoracic deformity and hypercalcemia. The plasma immunoreactive parathyroid hormone level allows the diagnostic. This case, with diffuse hyperplasia of water-clear cells type, develops rickets of vitamin D deficiency before surgery. A large parathyroidectomy (7/8) was performed and the child is normo-calcemic 2 years after. The time of surgery is function of calcium level. PMID- 4022716 TI - [Acute leukoencephalitis of measles. Apropos of 10 cases]. AB - Authors report 10 cases of acute measles encephalitis from the last five years. They emphasize its only mode of beginning and the gravity of its sequelae. PMID- 4022717 TI - [Coexistence of late spondyloepiphyseal dysplasia and congenital megaloblastic anemia with proteinuria in the same family]. AB - A case of spondyloepiphyseal dysplasia tarda was noted in a dwarf (130 cm tall) 18 years old boy associated with congenital megaloblastic anemia and proteinuria. His two sisters and a cousin are also suffering from similar hematologic disorder. One of his brothers, 145 cm tall, is also involved by spondyloepiphyseal dysplasia, but there is no known hematologic abnormalities. Review of family history revealed that two aunts from mother's side were deceased in adulthood following a chronic anemic disease. The findings in this anemia are compatible with Imerslund-Grasbech syndrome and coexistence of these two rare genetic disorders in a single family has not been reported previously. PMID- 4022718 TI - [Pseudo precocious puberty in the McCune-Albright syndrome]. AB - McCune Albright Syndrome is characterized by the triad of polyostostic fibrous dysplasia of bones, skin pigmentation (cafe au lait-spots) and sexual precocity. The authors report a case of a 7 years girl with this syndrome in whom the sexual precocity is due to an autonomous hyperfunctioning of luteinized follicular cysts of ovary. The pathogenic mechanisms of this autonomy are debate. PMID- 4022720 TI - Validation of a nonverbal instrument for pain location descriptions in children. PMID- 4022719 TI - [Complications of pyelo-ureteral duplications in children and their surgical treatment. Apropos of 69 cases (78 pathogenic duplications)]. AB - The authors report their experience on the surgical treatment of 69 infants and children with pyelo-ureteral duplication. Urinary infection was the main revealing symptom (52 cases). Vesico-ureteral reflux was the major associated anomaly (39 cases) involving most often the lower pole ureter; the surgical correction of the reflux was performed according to the technique of Cohen with a favorable outcome in all cases. Because of poorly functioning and dysplastic upper renal segment, partial upper pole nephrectomy was performed in 8 among 12 cases of associated ectopic ureteral orifice and in 9 among 15 cases of associated ureterocele. A reimplantation of the ureter was made possible in 3 cases of ectopic ureteral orifice and in 5 cases of ureterocele with little corresponding renal lesions. With the experience of one neonate who died from septic shock following partial nephrectomy there were no other post-operative complications in this series. PMID- 4022721 TI - Intuition, cognitive style, and hemispheric processing. AB - 200 undergraduate volunteers were administered Westcott's Test of Intuitive Ability, Witkin's Group Embedded Figures Test, Paivio's Revised Individual Differences Questionnaire, and visual and aural dominance measures using a three field tachistoscope and dichotic listening device, respectively. Field dependence was consistently related to poorer intuitive performance. No sex-related differences were found on intuition, embedded figures, Paivio's questionnaire, or dominance scores although the amount of intuition explained by cognitive style and dominance differed by hand and gender. Visual-verbal style was not associated with dominance while the relation of field dependence-independence and dominance was inconsistent. Neither dominance nor visual-verbal style was consistently related to intuition although complicated associations were indicated by hand and sex, suggesting differences in cognitive organization. PMID- 4022722 TI - Development of sign-based perception by deaf children. AB - In this study the sign-based perceptual abilities of 59 deaf children are investigated. Like many hearing speaking children, deaf signing children appear to perceive isolated lexical items based on the formational parameters of those items. Also, deaf signers show trends similar to those exhibited by hearing speakers for the development of the perceptual ability necessary to distinguish between minimal pairs within their respective language systems. PMID- 4022723 TI - Interindividual differences in acuity for odor and aroma. AB - To determine the olfactory acuity of 27 subjects a sensory test was presented which was divided into 4 subtests, 2 for nasal and 2 for oral stimulation. Each subtest contained 28 (4 substances X 7 concentrations) olfactory detection tasks (items). The substances used were lemon and rum aroma as well as ethyl butyrate and amyl acetate, the solvents tap water and sugared tap water. Analysis showed that the test provided a clear differentiation between subjects of low, medium, and high olfactory acuity. The intercorrelations among the test substances and the split-half reliabilities of the subtests proved relatively high, whereas only moderate to low intercorrelations among the subtests were found. This was considered an effect of intraindividual variations of olfactory sensitivity. Finally, some conclusions for the construction of acuity tests for odor and aroma are presented. PMID- 4022724 TI - Tactile stimulation and interhemispheric communication by learning disabled children: an exploratory study. AB - 33 right-handed, learning disabled children aged 8-10 yr., 11-13 yr., and 14-16 yr. were presented a tactile discrimination task. Pairs of fabrics of different or the same texture were presented to the same hand (uncrossed condition) or alternating hands (crossed condition). Analysis indicated that the total number of crossed errors was significantly greater for the youngest children. There were no significant differences between the groups for the uncrossed condition. These results suggest that younger learning disabled children may experience greater difficulty on a task which required interhemispheric transfer. PMID- 4022725 TI - Physical exercise, social background, and the well-being of older adult women. AB - 28 older women participating in an exercise program were compared to 30 older women not participating in an exercise program on two behavioral measures. There were no significant main effects for participation-nonparticipation in an exercise program. Significant main effects were found, however, for each of three social variables. PMID- 4022727 TI - A magnitude-estimation response pool for production of lingual vibrotactile magnitudes. AB - The present pilot study was designed to obtain samples of numerical vibrotactile magnitude estimations from two groups of 37 randomly selected subjects (Mage = 22.04 yr.) and to determine if these numbers were statistically equivalent. Analysis showed the numerical responses of the two groups of subjects were statistically equivalent. It was suggested that they might be viewed as a representative sample of magnitude-estimation numbers that could be employed in experimentation on lingual vibrotactile magnitude production. PMID- 4022726 TI - Multifactorial assessment of reading disability: identifying the best predictors. AB - A multifactorial diagnostic assessment battery was evaluated using data obtained from 105 reading-disabled children and their matched controls (total N = 210). A stepwise discriminant function analysis selected five nonreading measures from among 16 as the best diagnostic predictors of reading disability. These measures included WISC-R Information and Digit Span, self-reported family histories of reading problems, and tests of symbol-processing speed and letter fluency. PMID- 4022728 TI - Level of aspiration and performance of chronic psychiatric patients on a simple motor task. AB - The level of aspiration and performance was examined for 25 male psychiatric inpatients whose mean age was 57.4 yr. and mean length of hospitalization was 23.6 yr. For a simple motor task involving flipping a plastic chip over a goal line, each patient expressed the ward and his personal pretask levels of aspiration, performed the task, and expressed his personal posttask aspiration. The expressions of both the ward and pretask levels of aspiration were less than the mean score of a nonhospitalized referent group. Both performance and posttask levels of aspiration were greater than the pretask level. More patients predicted they would perform worse than the other patients on the ward than predicted they would perform better. The patients appropriately shifted their levels of aspiration either up after success or down after failure. The results were discussed according to expectations from classical theory as well as findings with schizophrenics. Implications for further research were discussed. PMID- 4022729 TI - Laterality of cerebral function: relations with anxiety, repression, and perception. AB - Based on two factor analyses of data from 67 right-handed undergraduates, a laterality quotient based on forward memory spans, spatial minus digit, divided by their sum, was devised. The hemispheric balance factor for which this quotient served as the principal marker had significant positive loadings by the laterality quotient for the Edinburgh Handedness Questionnaire and by a measure of repressive tendencies, the Marlowe-Crowne Social Desirability Scale. Scores from this factor were positively related to global as opposed to analytic perception as measured by the Navon tachistoscopic task. This factor was unrelated to the trait anxiety and working short-term memory factors which also emerged. Trait anxiety was negatively related to global perception. The results raise the possibility that greater degrees of right-handedness may be related to the release of the nondominant right hemisphere from inhibition and that working short-term memory may not be lateralized. PMID- 4022730 TI - Compliance with homework to employ self-instructions in controlling ice water pain: an analogue to counseling. AB - 40 women were taught to use self-statements to cope with pain caused by ice water. The trainer used four different strategies for reassigning a homework task of using self-statements to cope with pain produced by immersing one hand in ice water. The strategies were equally effective in eliciting compliance with the homework assignment. PMID- 4022731 TI - Death anxiety as a semantic conditioned suppression paradigm. AB - Death anxiety and more severe forms of thanatophobia are encountered frequently in the clinical population. However, approaches that allow behavioral solutions to these experiences are conspicuously absent in the literature. From an operant perspective, death anxiety arises from repeated exposures to direct and implicit forms of the statement "I will die". It is the semantic equivalent of a conditioned suppression paradigm. Historically, the human organism has attempted to reduce the aversive consequences of this reinforcement schedule by extinguishing one of its three components. The "solutions" characterize the fundamental philosophical and religious treatments of death anxiety. A behavioral semantics approach is proposed as suitable for dealing with death anxiety of a religious, educated young adults, particularly those dying of terminal diseases. PMID- 4022732 TI - Improving the test-taking skills of learning-disabled students. AB - 16 learning-disabled second- and third-grade students were matched on previous years' achievement scores and grade and assigned at random to experimental and control conditions. Students in the experimental condition were given 8 20-min. sessions of training in test-taking skills particular to the Stanford Achievement Test. Analysis of test scores indicated trained students scored significantly higher on one subtest of a shortened version of the test than students who had not been trained. PMID- 4022733 TI - Geophysical variables and behavior: XXVIII. Group health-care-seeking behavior and meteorological variables. AB - Outpatient visits to a "subtropical" military medical clinic (group health-care seeking behavior) were correlated to weather variables via stepwise linear regression. Despite several significant sets of correlations, quantitative (r, r2, multiple R, multiple R2 and x2) and qualitative (matrix) analyses did not support the existence of lag/causal relationships between weather and behavior. The largest amount of variance (r2) attributable to an individual weather variable was 3% for lower (minimum) daily mean wind speed per month. No regression accommodated more than 36% of variance. Thus, 64% of variance was due to unidentified variables. A winter "seasonal effect" (December and January) was tentatively identified. Group influenza immunizations and 3-day holidays preceded increased visits. PMID- 4022734 TI - Interhemispheric transfer of visual information in schizophrenics. AB - Groups of 12 male schizophrenic inpatients and 12 normal controls of the same age, sex, and schooling underwent a tachistoscopic test. Each subject was shown an alphabetical letter which he subsequently had to recognize among various other alphabetical letters also shown tachistoscopically. The visual hemifields of the two displays were ipsilateral and crossed. Relative to the normal group the schizophrenics showed higher perceptual thresholds, lower over-all mean performance, and greater lateralization. The results are discussed in terms of rigidly and poorly integrated systems of analysis of information between one hemisphere and the other for schizophrenic patients. PMID- 4022735 TI - Learning effects of knowledge of results upon time estimation. AB - College students of both sexes served as their own controls to test three hypotheses in each of two separate experiments designed to assess the learning effects of knowledge of results upon time estimation. The results indicated that (1) knowledge of results in the form of feedback to the nearest hundredth of a second significantly increased the mean accuracy of time estimations obtained by the method of production, (2) that knowledge of results significantly decreased the variance of the time estimations, and (3) that sex difference as a main effect was not significant in either experiment. A major conclusion of the present study was that variance represents an authentic and independent measure of learning. PMID- 4022736 TI - Antidepressant treatment of children: clinical relapse is unrelated to tricyclic plasma concentrations. AB - Plasma concentrations of imipramine and amitriptyline and their desmethylated metabolites were measured in 20 children being treated for major depressive illness 2 wk. and 5 to 10 wk. after achieving drug dosages of 2.25 mg/kg body weight. At 2 wk. all children had exhibited clinical improvement, but by 10 wk. 4 of the 10 children treated with imipramine and 5 of the 10 children treated with amitriptyline had experienced clinical relapse of depressive symptoms. Tricyclic antidepressant plasma concentrations and ratios were comparable in the subgroups of children who maintained their clinical improvement and those who relapsed. There was no evidence of a systematic decline in plasma tricyclic antidepressant concentrations in those children who relapsed. PMID- 4022737 TI - Audiospatial integration. AB - A method to examine audiospatial integration was developed through studies of normal and brain-injured patients. The method used a sound source sequentially outlining a spatial pattern within an array of 100 loudspeakers. For 48 subjects tested with this method, the presence or absence of visual cues had no effect in audiospatial processing. Eye movements also did not match the perceived sound patterns. Significantly higher hit rates were obtained by placing the panel of loudspeakers in front, behind or above the subject rather than on the left or right. These differences were observed with involuntary but not with voluntary head-fixation. Theoretical concepts of audiospatial processing are discussed. PMID- 4022738 TI - Temporal lobe signs and reports of subjective paranormal experiences in a normal population: a replication. AB - Correlations (r = 0.50) were found between the numbers of different psi (paranormal) experiences and the numbers of temporal lobe signs within a population of university students (n = 99). The strongest correlation of 0.60 occurred with a cluster of signs that are similar to symptoms reported by patients who show chronic foci in the mesiobasal temporal lobe. However, there were no significant correlations between numbers of different psi experiences and clusters of control items or a lie scale. Specific analyses of the 140 items of the inventory indicated only 23 reached statistical criterion (p less than .001). Of these 17 were direct temporal lobe signs that implied deepened affect, auditory-vestibular experiences (vibrations, hearing one's name called), olfactory auras, perseveration ("forced" thinking), depersonalization, and sense of the personal. Five items involved beliefs about exotic phenomena or philosophical ideas. Only one item was from a control cluster. These results support the hypothesis that mystical or paranormal experiences are associated with transient electrical foci within the temporal lobe of the human brain. The repeated occurrence of these experiences within normal individuals may be embedded within a more complex symptomatology of temporal lobe signs. PMID- 4022739 TI - Size of human figure drawing and Goodenough-Harris scores of pediatric oncology patients: a pilot study. AB - Human figure drawings of 12 pediatric oncology patients were significantly smaller in height, width, and area than were drawings of 12 school children and 12 pediatric general surgery patients paired for sex and age. The Goodenough Harris scores of the cancer patients' drawings were also significantly lower than those of both school and general surgery groups. It is hypothesized that anxiety, lowered self-esteem, and the effects of chemotherapy contributed to these findings. PMID- 4022740 TI - Perception of life stress events by older and younger women. AB - 24 women over 60 yr. and 24 younger women rated the severity of life stress events drawn from a pool of events occurring to elderly people. There were no over-all age differences, but rather strong agreement on which events were most threatening. There was some evidence, however, that the old rated 'severe' death events as less threatening than younger women. PMID- 4022741 TI - Developmental trends in dichhaptic lateralization. AB - Two studies on developmental trends in dichhaptic lateralization for nonlinguistic stimuli were conducted on school-aged children. Study 1 included 60 students in Grades 1, 5, and 9. Study 2 included 200 students from Grades 2, 4, 6, 8, and 10. Both studies showed significant age-related increases in over-all dichhaptic accuracy. In Study 2 a significant left-hand advantage for all subjects as well as an over-all advantage for boys were noted. Significant interactions indicated different developmental trends for boys and girls but did not show clear patterns in the development of lateralization. PMID- 4022742 TI - Space flight: III. Isolation of perceptual variable in parabola flight sickness with countermeasure to lower gastric pH. AB - Two factors of space sickness are discussed, one perceptual and the other physiological. Data from 2 adults on KC-135 airplane parabolic flights. PMID- 4022743 TI - Motoric indicators of laterality and determination of lateral dominance in schizophrenia. AB - The literature suggests that schizophrenics exhibit reduced or reversed cerebral lateral dominance relative to normal control subjects. An hypothesis which predicted reduced or reversed cerebral laterality for schizophrenics was tested on 60 young, familially right-handed males, with 20 men in each of the following three groups: schizophrenic inpatients, nonschizophrenic psychiatric inpatient controls, and normal controls. The subjects were administered a battery of seven measures of cerebral laterality. The application of multivariate statistical techniques showed groups did not differ significantly in the degree or the direction of their cerebral lateral dominance. Also there were no significant correlations between the measures of laterality. The findings suggest that cerebral lateral dominance is not necessarily altered concomitantly with psychopathology but rather that it is a complex phenomenon which may not be reliably determined on the basis of simple behavioral characteristics. PMID- 4022744 TI - Comparison of self- and peer-perceptions of mentally retarded children. AB - The self- and peer-perceptions of 40 mentally retarded children (mental ages 6 yr. to 12 yr.) were compared. Age differences were not obtained. Affective reports of likes and dislikes predominated the self-perceptions. Situational, external descriptions of behavior characterized the peer perceptions. These qualitative results are similar to the self- and peer-perceptions of nonretarded children. PMID- 4022745 TI - Analysis of temporal suppression mechanism in binocular rivalry. AB - A method for analyzing the temporal suppression mechanism in binocular rivalry is described. A test pattern was presented to one eye and a suppressing pattern to the other eye after varying time intervals. The subject was instructed to report the frequency of nonsuppression phases of the test pattern immediately after presentation of the suppressing pattern. Analysis indicated that the test pattern was never suppressed at the 0-msec. stimulus onset asynchrony and the nonsuppression probabilities decreased as the onset asynchrony increased. Moreover, resistivity to contralateral suppression was greater when the test pattern was projected to the dominant eye. PMID- 4022746 TI - The effects of peripheral movement and flicker on the detection thresholds of sinusoidal gratings. PMID- 4022747 TI - Retention in perceptual memory: a review of models and data. PMID- 4022748 TI - Achromatic color categories. PMID- 4022749 TI - Effects of single-session repetitive judgments on magnitude estimation scales for lingual vibrotactile sensation. PMID- 4022750 TI - Serial-pattern structure and temporal-order recognition. PMID- 4022751 TI - The effects of changes in curve geometry on magnitude estimates of road-like perspective curvature. PMID- 4022752 TI - Cognitive interference in prism adaptation. PMID- 4022753 TI - How does speed change affect induced motion? PMID- 4022754 TI - On the nature of inducing forms generating perceptions of illusory contours. PMID- 4022755 TI - Stimulus presentation frequency in brightness discrimination and generalization: a test of adaptation-level and signal-detection interpretations. PMID- 4022756 TI - Describing perceptual information about human growth in terms of geometric invariants. PMID- 4022757 TI - Matching of facial features: continuous processing, improper filtering, and holistic comparison. PMID- 4022758 TI - Effect of intermixed foveal and parafoveal presentation on same-different judgments: evidence for a criterion-inertia model. PMID- 4022759 TI - Space constancy and corollary discharge. PMID- 4022760 TI - The bactericidal activity of aqueous disinfectants applied on living tissues. AB - Thirteen antiseptic aqueous solutions intended for the disinfection of living tissues were compared in regard to their microbicidal effectiveness towards. Staphylococcus aureus and Pseudomonas aeruginosa. Six antiseptics, which contain boric acid, eosine, hydrogen peroxide or an organic mercury compound as the active substance, did not fulfil the requirements of the preliminary in vitro test. The seven other preparations were examined in a practical test, in which bactericidal activity was assessed on artificially contaminated intact skin after exposures of 15 s and 60 s. The most active solution appeared to be 0.5% tosylchloramide sodium, followed by 0.05% chlorhexidine with 0.5% cetrimide. The other preparations, namely 0.05% chlorhexidine without cetrimide, 0.245% chloroxylenol, 0.04% clorofene, 10% povidone-iodine and 0.2% tosylchloramide sodium, were less active in this practical test. PMID- 4022761 TI - Determination of the stability of tetracycline suspensions by high performance liquid chromatography. AB - High performance liquid chromatography was used to examine the stability of tetracycline suspensions, prepared according to the Formulary of the Dutch Pharmacists and the National Formulary v (Belgium). The influence of the nature of the buffer salt, of the pH, and of the temperature and time of storage are discussed. At slightly acid pH (4 to 5.5) and at room temperature suspensions are stable for at least three months. PMID- 4022762 TI - A general system for the automation of a backflush equipped gas chromatograph and its application in the determination of fluoride in plasma and faeces. AB - A fully automated system is described in which a gas chromatograph equipped with a backflush valve is automatically operated under the control of a specially designed timer unit. The system requires minimum data acquisition due to the selection of the signals to be integrated while waste of recorder paper is also avoided. It has the capability of unattended operation of fifty samples which--in the case of fluoride determination--are chromatographed in about four hours. PMID- 4022763 TI - Degradation products of the promethazine radical cation. AB - The degradation products of the promethazine radical cation, generated from promethazine with horseradish peroxidase/H2O2, have been investigated. Several products have been identified which resulted from fission of the bond between the two ethanamine carbon atoms of the N10 side chain. The main product (approx. 90%) was identified as 10-formyl-5-oxophenothiazine. The likely structure of three minor products was also elucidated. The degradation of the promethazine radical cation is different from that of radical cations derived from the propanamine side chain containing phenothiazine drugs. PMID- 4022764 TI - [Initial results from a randomized study in the counties of Kopparberg and Ostergotland (the WE project). Reduced mortality in breast cancer through health control with mammography]. PMID- 4022765 TI - [Diarrhea as a clinical problem]. PMID- 4022766 TI - [Rotavirus gastroenteritis in children]. PMID- 4022767 TI - [Humorally mediated diarrheas]. PMID- 4022768 TI - [Computers, an aid in clinical research]. PMID- 4022769 TI - A highly polymorphic region 3' to the human type II collagen gene. AB - We have characterised a highly polymorphic region 1.3kb downstream of the human Type II collagen gene. It consists of a highly AT-rich tandem repetitive region (minisatellite) approximately 650bp long. Two alleles had been observed previously, differing in size by approximately 300bp. When this region was cloned from four unrelated individuals carrying the larger allele, DNA sequence data identified three alleles, suggesting far higher polymorphism than was originally supposed. This minisatellite was shown to be present in a single copy in the human genome, and to have arisen after the divergence of Old and New World monkeys. PMID- 4022770 TI - A comparison between mammalian and avian fast skeletal muscle alkali myosin light chain genes: regulatory implications. AB - A single locus in the mouse, rat and chicken encodes both alkali myosin light chains, MLC1F and MLC3F. This gene has two distinct promoters and gives rise to two different primary transcripts, which are processed by alternative and different modes of splicing to form MLC1F and MLC3F mRNAs. The MLC1F/MLC3F gene is very similar between mouse, rat and chicken, in terms of its overall structure, the length and location of the introns, and the splice site consensus sequences. Nucleotide sequences of coding regions are very conserved but 3' and 5' non coding regions of the mRNAs have diverged. In the MLC1F promoter regions, several blocks of nucleotides are highly conserved (more than 70% homology), especially a sequence of about 70 nucleotides, located between positions -80 and 150 relative to the Cap site. Conserved blocks of homology are also found in the MLC3F promoter regions, although the common sequences are shorter. The presence of such highly conserved nucleotide sequences in the 5' flanking regions suggests that these sequences are functionally important in initiation of transcription and regulation of expression of this complex gene. Primer extension experiments indicate multiple cap sites for MLC3F mRNA. PMID- 4022771 TI - Characteristics of trypanosome variant antigen genes active in the tsetse fly. AB - Trypanosoma brucei contains a repertoire of more than 100 different genes for Variant Surface Glycoproteins (VSGs). A small and strain-specific fraction of these genes is expressed in the salivary glands of the tsetse fly (M-genes), giving rise to metacyclic Variable Antigen Types (M-VATs). Antibodies produced in a chronic trypanosome infection initiated by syringe inoculation of bloodstream forms into mammals (i.e. against B-VATs), will react with most of the M-VATs suggesting that these B-VATs express VSG genes that are similar or identical to M genes. We have cloned DNA complementary to the VSG mRNA of four of such B-VATs and used this to characterize the corresponding VSG genes. In three of the four VATs we find a single VSG gene hybridizing with the cDNA probe and we provide supporting evidence that this gene is expressed as an M-gene. In the bloodstream repertoire these genes appear to be activated by duplicative translocation to another telomere. In all four variants the putative M-genes are telomeric and in the three cases where the location of the genes on chromosome-sized DNA molecules could be determined, the genes were located in large DNA, whereas the majority of the telomeric VSG genes are in chromosomes less than 1000 kb. Our results are best explained by models for M-gene activation involving telomeric expression sites for these genes which are separate from those used by bloodstream forms. The implications of these results for vaccination are discussed. PMID- 4022772 TI - Conserved sequences in both coding and 5' flanking regions of mammalian opal suppressor tRNA genes. AB - The rabbit genome encodes an opal suppressor tRNA gene. The coding region is strictly conserved between the rabbit gene and the corresponding gene in the human genome. The rabbit opal suppressor gene contains the consensus sequence in the 3' internal control region but like the human and chicken genes, the rabbit 5' internal control region contains two additional nucleotides. The 5' flanking sequences of the rabbit and the human opal suppressor genes contain extensive regions of homology. A subset of these homologies is also present 5' to the chicken opal suppressor gene. Both the rabbit and the human genomes also encode a pseudogene. That of the rabbit lacks the 3' half of the coding region. Neither pseudogene has homologous regions to the 5' flanking regions of the genes. The presence of 5' homologies flanking only the transcribed genes and not the pseudogenes suggests that these regions may be regulatory control elements specifically involved in the expression of the eukaryotic opal suppressor gene. Moreover the strict conservation of coding sequences indicates functional importance for the opal suppressor tRNA genes. PMID- 4022773 TI - Efficient octopine Ti plasmid-derived vectors for Agrobacterium-mediated gene transfer to plants. AB - A two-component cloning system to transfer foreign DNA into plants was derived from the octopine Ti plasmid pTiB6S3. pGV2260 is a non-oncogenic Ti plasmid from which the T-region is deleted and substituted by pBR322. pGV831 is a streptomycin resistant pBR325 derivative that contains a kanamycin resistance marker gene for plant cells and a site for cloning foreign genes between the 25-bp border sequences of the octopine T-region. Conjugative transfer of pGV831 derivatives to Agrobacterium and cointegration by homologous recombination between the pBR322 sequences present on pGV831 and pGV2260, can be obtained in a single step. Strains carrying the resulting cointegrated plasmids transfer and integrate T-DNA into the genome of tobacco protoplasts, and transformed tobacco calli are readily selected as resistant to kanamycin. Intact plants containing the entire DNA region between the T-DNA borders have been regenerated from such clones. In view of these properties we present pGV831 and its derivatives as vectors for efficient integration of foreign genes into plants. PMID- 4022774 TI - Base-base mismatches. Thermodynamics of double helix formation for dCA3XA3G + dCT3YT3G (X, Y = A,C,G,T). AB - Thermodynamic parameters for double strand formation have been measured for the sixteen double helices of the sequence dCA3XA3G.dCT3YT3G, with each of the bases A, C, G and T at the positions labelled X and Y. The results are analyzed in terms of nearest-neighbors and are compared with thermodynamic parameters for RNA secondary structure. At room temperature the sequence (Formula: see text) is more stable than (Formula: see text) and is similar in stability to (Formula: see text) and (Formula: see text) are least stable. At higher temperatures the sequences containing a G.C base pair become more stable than those containing only A.T. All molecules containing mismatches are destabilized with respect to those with only Watson-Crick pairing, but there is a wide range of destabilization. At room temperature the most stable mismatches are those containing guanine (G.T, G.G, G.A); the least stable contain cytosine (C.A, C.C). At higher temperatures pyrimidine-pyrimidine mismatches become the least stable. PMID- 4022775 TI - Human DNA sequences exhibiting gamete-specific hypomethylation. AB - Three human DNA sequences have been cloned from DNA regions which are strikingly undermethylated in sperm, highly methylated in adult somatic tissues, and methylated to an intermediate extent in tissues of extraembryonic origin. It is proposed that some such DNA sequences may function specifically early in embryogenesis or during gametogenesis. They may be subsequently extensively methylated in the embryonic cell lineage and methylated to a lesser extent in extraembryonic tissues in order to allow embryogenesis to proceed. PMID- 4022776 TI - Histone H1 and HMG 14/17 are deposited nonrandomly in the nucleus. AB - We have studied the assembly of histone H1 and the high mobility group nonhistones 14/17 by isopycnic analysis after crosslinking density labeled MSB cell nuclei or chromatin. Carbodiimide crosslinking produces dense poly-H1 and hybrid density H1-H2A histone dimers, indicating that new H1 is deposited nonrandomly, albeit nonconservatively relative to new core histones. Core histone HMG crosslinking with succinimidyl propionate yields dense HMG 14 in uniformly dense particles and new HMG 17 crosslinked to both dense and light protein, implying that HMG 14 and 17 each deposit nonrandomly; but differently with respect to new core octamers. Propionimidate crosslinking yields dense H1-HMG 17 dimers, suggesting that the interactions of new 14/17 with H1 (new HMG 14-old H1, new HMG 17-new H1) are reciprocal to their interactions with the core histones. PMID- 4022777 TI - Isolation and sequence of cDNA clones coding for a member of the family of high mobility group proteins (HMG-T) in trout and analysis of HMG-T-mRNA's in trout tissues. AB - A specific oligonucleotide has been used to isolate a cDNA prepared from the mRNA for a trout High Mobility Group (HMG) protein closely related to trout HMG-T and bovine HMG 1 and 2 proteins. The sequence isolated more closely resembles bovine HMG-1 than the previously sequenced HMG-T protein in regions corresponding to the N terminal half of the protein. Northern blot analysis at low stringency indicated that 2 related sequences are expressed in total trout testis mRNA. Southern blots of total trout DNA indicate that several different forms of the homologous sequence are present in the trout genome and an estimate of copy number by dot-blot shows 4 HMG-T genes per trout sperm DNA equivalent. Analysis of mRNA from several trout tissues, including testis, liver and kidney indicates that expression of genes for histones and the larger HMG proteins in trout is not closely coupled. PMID- 4022778 TI - Characterization of mouse 45S ribosomal RNA subspecies suggests that the first processing cleavage occurs 600 +/- 100 nucleotides from the 5' end and the second 500 +/- 100 nucleotides from the 3' end of a 13.9 kb precursor. AB - Mouse fibroblasts labeled 1-9 h with 3H-uridine contained radioactive 45S rRNA subspecies of 13.9, 13.3, and 12.8 kb, as determined by hybrid-selection with rDNA plasmids and by electrophoresis in agarose-formaldehyde. The 13.9 kb subspecies contained 5' and 3' terminal rDNA sequences known from the work of Grummt and colleagues to be at or near the ends of the primary transcript. The 13.3 kb subspecies contained the 3' terminal sequence but lacked the 5' terminal sequence. The 12.8 kb subspecies lacked both terminal sequences. Washed nuclei produced one discrete species of 13.9 kb. The results suggested that synthesis of the primary transcript terminated 500 +/- 100 nucleotides beyond the 3' end of 28S rRNA, that the first processing cleavage occurred 600 +/- 100 nucleotides from the origin of synthesis, and the second cleavage occurred near the 3' end of 28S rRNA. Changes in relative radioactivities among the subspecies after serum stimulation or after treatment with low concentrations of cycloheximide suggesting that processing was not perfectly coupled with synthesis and that cycloheximide inhibited one cleavage more than others. PMID- 4022779 TI - Nuclease-hypersensitive sites in chromatin of the estrogen-inducible apoVLDL II gene of chicken. AB - DNAseI-hypersensitive sites were localized in apoVLDL II chromatin from chicken. In the liver two sites at 1.75 and 1.0 kb upstream from the cap-site are present before the gene is activated. After induction by estradiol a number of additional sites appear, three in the promotor region of the gene, one within the coding region and two behind the poly-A signal. These sites disappear when the expression of the gene is shut off upon estradiol withdrawal. All sites appear to be tissue-specific in that they are not found in other tissues of the rooster. However, in oviduct of the laying hen we find a hypersensitive site at 1.6 kb in front of the gene. PMID- 4022780 TI - The C. elegans vitellogenin genes: short sequence repeats in the promoter regions and homology to the vertebrate genes. AB - The nematode Caenorhabditis elegans contains a small family of vitellogenin genes which is expressed abundantly, but only in the intestine of the adult hermaphrodite worm. In order to identify possible regulatory elements, we have sequenced the DNA surrounding the 5' ends of five of the six genes. Contained within regions which have largely diverged from one another, two different heptameric sequences are found repeated within the first 200 bp upstream of each of the genes. The first sequence, TGTCAAT, is present as a perfect heptamer at least once upstream of each gene. It is repeated in both orientations four to six times in each 5' flanking region, allowing a one-base mismatch. The second sequence, CTGATAA, is also present as a perfect heptamer in a restricted region upstream of each gene. These two sequence elements may be involved in regulation of the vitellogenin genes. Remarkably, the CTGATAA sequence is present in a similar location in the promoter regions of vertebrate vitellogenin genes. In fact, our data reveal a surprising degree of similarity between the nematode and vertebrate vitellogenins. PMID- 4022781 TI - Structural determination of the ultraviolet light-induced thymine-cytosine pyrimidine-pyrimidone (6-4) photoproduct. AB - Ultraviolet light induces damage to DNA, with the majority of the damage expressed as the formation of cyclobutane dimers and pyrimidine-pyrimidone (6-4) photoproducts. The (6-4) photoproducts have been implicated as important UV light induced premutagenic DNA lesions. The most abundant of the (6-4) products is the thymine-cytosine pyrimidine-pyrimidone (6-4) photoproduct, or TC (6-4) product. The structure of the TC (6-4) product was deduced by proton NMR, IR, and fast atom bombardment mass spectroscopy, and the product was found to differ from the previously described photoadduct, Thy(6-4)Pyo, by the presence of an amino group at the 5 position of the 5' pyrimidine. The implications of this structure on DNA base pairing and the induction of ultraviolet light-induced mutations are discussed. PMID- 4022782 TI - Prediction of splice junctions in mRNA sequences. AB - A general method based on the statistical technique of discriminant analysis is developed to distinguish boundaries of coding and non-coding regions in nucleic acid sequences. In particular, the method is applied to the prediction of splicing sites in messenger RNA precursors. Information used for discrimination includes consensus sequence patterns around splice junctions, free energy of snRNA and mRNA base pairing, and statistical differences between coding and non coding regions such as periodic appearance of specific bases in coding regions reflecting the non-random usage of degenerate codons. Given the reading frame of an exon (but not the exon/intron boundaries), the method will predict the following exon, namely, the intron to be excised out. When applied to human sequences in the GenBank database, the method correctly identified 80% of true splice junctions. PMID- 4022783 TI - A new synthesis of certain 7-(beta-D-ribofuranosyl) and 7-(2-deoxy-beta-D ribofuranosyl) derivatives of 3-deazaguanine via the sodium salt glycosylation procedure. AB - A facile synthesis of 7-beta-D-ribofuranosyl-3-deazaguanine (1) and certain 8 substituted derivatives of 1 via the sodium salt glycosylation method has been developed. Glycosylation of the sodium salt of methyl 2-chloro(or methylthio) 4(5)-cyanomethylimidazole-5(4)-carboxylate (5 and 13b) with 2,3,5-tri-O-benzoyl-D ribofuranosyl bromide (6) gave exclusively methyl 2-chloro(or methylthio)-4 cyanomethyl-1-(2,3, 5-tri-O-benzoyl-beta-D-ribofuranosyl)imidazole-5-carboxylate (7 and 14a), respectively. Ammonolysis of 7 and 14a provided 6-amino-2-chloro(or methylthio)-3-beta-D-ribofuranosylimidazo-[4,5-c]pyridin-4(5H)-one (11 and 17), which on subsequent dehalogenation (or dethiation) gave 1. Similarly, reaction of the sodium salt of 5 and 13b with 1-chloro-2-deoxy-3,5-di-O-p-toluoyl-alpha-D erythro-pentofuranose (8), and ammonolysis of the glycosylated imidazole precursors (9 and 16) gave 6-amino-2-chloro(or methylthio)-3-(2-deoxy-beta-D erythro-pentofuranosyl) imidazo[4,5-c]-pyridin-4(5H)-one (10a and 15), respectively. Dehalogenation of 10a or dethiation of 15 gave 2'-deoxy-7-beta-D ribofuranosyl-3-deazaguanine (10b). This procedure provided a direct method of obtaining 10b without the contaminating 9-glycosyl isomer 4. PMID- 4022784 TI - Two RFLPs identified by a human chromosome #2 clone at 2p15-2p16 (HGM8 assignment no. D2S5). PMID- 4022785 TI - Effects of age and health on the euthyroid reference ranges for serum free thyroxine and free triiodothyronine. AB - Age-related trends in serum free thyroxine (FT4) and free triiodothyronine (FT3) concentrations were measured in 7248 euthyroid subjects (age-range 3 months to 106 years). 5700 were patients referred to hospitals for investigation of suspected thyroid dysfunction, but who were diagnosed euthyroid. 1548 were healthy blood donors (age-range 18-63 years) with no indication of thyroid dysfunction. FT4 concentrations were little affected by the age, the sex or the state of health of the subjects in either group. Serum FT3 concentrations were significantly affected by both age and health factors. The upper limit of the euthyroid reference range for young subjects up to 15 years was about 20% higher (10.4 pmol/l) than for adult subjects older than 25 years (8.8 pmol/l). The change in the upper limits typical of young subjects to that typical of adults occurred steadily over the decade 15-25 years. After this age, little further change occurred, especially in healthy subjects. Additionally, the lower limit of the euthyroid range for FT3 was extended by the inclusion in the reference group of patients referred to hospitals. Compared with the lower limit of the FT3 range for healthy subjects (5 pmol/l), the corresponding limit for referred subjects (young or adult) was 3.5-3.8 pmol/l. Broadening of the FT3 reference range was probably brought about by a significant number of patients in the hospital referred group with the "low-T3 syndrome" of mild non-thyroidal illness. Accordingly, FT3 was inferior to FT4 in the discrimination of hypothyroidism, as FT4 was unaffected by this phenomenon.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4022786 TI - [Blood picture changes in rats after 90Y-citrate administration]. AB - Therapeutic doses of 90Y-citrate show a high selective accumulation in bone. Bone marrow is the critical organ. Investigations in rats show a decrease of leucocytes, erythrocytes and thrombocytes depending on dose. A significant decrease of the leucocytes and thrombocytes was seen with 0.5 mCi (17.5 MBq) 90Y per kg bodyweight, with 2.0 mCi (74 MBq) also of the erythrocytes. This would be equivalent to a dose of 35 to 140 mCi (1.295 to 5.18 GBq) for a normal patient (70 kg). Therefore, a single dose of 10 mCi (370 MBq) of 90Y-citrate should be tolerated by a tumor patient without any blood cell depression, if there was no prior chemotherapy. PMID- 4022787 TI - Change of pharmacokinetic parameters of 131I-hippuran caused by heparin. AB - The radiochemical purity of 131I-hippuran determined by radiochromatographic analysis using Whatman No 3 MM paper and a mixture of n-butanol, acetic acid and water as developer, was 97.3 +/- 1.2%. O-131IB acid and less than 1% of free 131I were separated from the preparation. No radioactivity which would correspond to O 131IB acid was observed on the radiochromatogram when 131I-hippuran was incubated with HSA and heparin. Protein binding of 131I-hippuran as a function of radiochemical purity, and HSA and heparin concentrations were determined by the method of equilibrium dialysis. No effect of radiochemical purity on protein binding of 131I-hippuran was observed, the value obtained being 1.3 +/- 0.1%. Higher HSA concentrations increased protein binding but decreased retention activity on the dialysing membrane. Heparin decreased protein binding of 131I hippuran by 47%. The biological half-times of excretion of 131I-hippuran with heparin were 4 min for the fast phase and 107 min for the slow phase. The results of biodistribution in experimental animals showed increased localization of 131I hippuran with heparin in the kidneys and liver during the first 15 min after injection. PMID- 4022788 TI - Preparation, quality control and application of 99mTc-gluco-ene-diolate for renal scanning. AB - A one-step freeze-dried Sn-glucose kit was developed to be labelled with technetium-99m. TLC, paper chromatography and gel chromatography column scanning techniques (GCS) were used for the determination of the labelling yield of the complex. High radiochemical purity was obtained (98%). In vivo distribution studies were performed in white rats. Maximum uptake in kidneys (28%) was achieved in 15-90 min. The blood disappearance curve studies of the labelled Sn(II)-gluco-ene-diolate in rabbits have shown two disappearance phases of activity from blood with biological half-times of 10 and 150 min for the fast and slow component respectively. PMID- 4022789 TI - Preparation and biokinetic studies of 99mTc-p-butyl-IDA for hepatobiliary scintigraphy. AB - A freeze-dried powder of tin-p-butyl-IDA to be labelled with 99mTc for hepatobiliary scintigraphy has been developed. Gel chromatography column scanning has been applied for evaluating the labeling efficiency of the complex under different conditions. The results of organ distribution studies in mice and of clinical investigations in human beings showed the stability of the radiopharmaceutical. The preparative 99mTc-p-butyl-IDA concentrates moderately well in the bile with a rapid blood clearance into hepatocytes, very low excretion in the urine and slow clearance into the bile. PMID- 4022790 TI - [An attempt at interpreting the linear correlation between the indicators of forced expiration: MTT and FEV1% FVC]. PMID- 4022791 TI - [Effect of verapamil on spirometric parameters during an attack of dyspnea in patients with bronchial asthma]. PMID- 4022792 TI - [Effect of verapamil on post-histamine bronchial spasm]. PMID- 4022793 TI - [Disorders of respiratory function in chronic pulmonary embolism]. PMID- 4022794 TI - [Pulmonary hypertension in a patient with pulmonary fibrosis and rheumatoid arthritis]. PMID- 4022795 TI - [Serum immunoglobulin changes in patients with mycotic infections treated with levamisole]. PMID- 4022796 TI - [Disaccharidases of gastric mucosa in gastroduodenal ulcer]. PMID- 4022797 TI - [Theophylline and its derivatives]. PMID- 4022798 TI - [Effect of 6-month motor rehabilitation on pulmonary ventilation after cardiosurgical operations]. PMID- 4022799 TI - [Hypereosinophilia syndrome or eosinophilic leukemia?]. PMID- 4022800 TI - [Significance of activation of oncogenes in neoplastic transformation]. PMID- 4022801 TI - [Mitral leaflet prolapse syndrome; correlation of data obtained by one dimensional echocardiographic and angiographic studies]. PMID- 4022802 TI - [Analysis of selected lithogenic factors in patients with active and non-active nephrolithiasis]. PMID- 4022803 TI - Effect of treatment on streptococcal pharyngitis: is the issue really settled? PMID- 4022804 TI - Detection of Giardia lamblia antigen in the feces by counterimmunoelectrophoresis. AB - The presence of Giardia lamblia antigen in stools of symptomatic and asymptomatic giardiasis patients was studied by counterimmunoelectrophoresis using anti-G. lamblia (Portland strain I) trophozoite antibodies. This test could detect antigen in feces of 94% of giardiasis patients. However, it failed to differentiate between symptomatic and asymptomatic Giardia infection. There were no false-positive results in children with other diseases. Antigen in the stools disappeared within 1 to 2 weeks after eradication of infection with specific treatment. The overall sensitivity of this test in detecting G. lamblia antigen in stool was 94%, and the specificity was 95%. PMID- 4022805 TI - Brain abscesses in infants and children. PMID- 4022806 TI - Central nervous system nocardiosis associated with a traumatic polymicrobial brain abscess. PMID- 4022807 TI - Contagiousness of zoster in a day care setting. PMID- 4022808 TI - Acute fulminant toxic encephalopathy associated with Mycoplasma pneumoniae infection. PMID- 4022809 TI - Congenital bacteremia due to Capnocytophaga. PMID- 4022810 TI - Isolated pulmonary cryptococcosis in a young adolescent. PMID- 4022811 TI - Neisseria gonorrhoeae ventriculoperitoneal shunt infection in a child. PMID- 4022812 TI - Hepatitis B risk from infectious discarded syringes. PMID- 4022813 TI - UVR-sensitive and UVR-resistant antigen-presenting cells. PMID- 4022814 TI - Miniature swine as an animal model in photodermatology: factors influencing sunburn cell formation. AB - Swine have played an important role as animal models in dermatological research. In order to evaluate the usefulness of pig skin in photodermatology, sunburn cell (SBC) formation in the epidermis of miniature swine and erythema production were studied. SBCs were readily formed in the epidermis of the swine by ultraviolet radiation. Suberythemal doses of broad-band UVB radiation were effective in producing SBCs, and there was a dose-response relationship between SBC formation and ultraviolet radiation. When SBC formation was related to ultraviolet radiation in terms of biological dose (i.e. minimal erythema dose) neither the spectral characteristics of the sources nor the degree of pigmentation in the skin affected the response. When SBC formation was related to physical dose (J/m2) the protection value of tanning was evident. These results, when coupled with the morphological and physiological similarities between human and porcine skin, demonstrate the usefulness of this animal model in photodermatology. PMID- 4022815 TI - Photoactivation of hyaluronidase by chlorpromazine. AB - The effects of UVA and chlorpromazine on the activity of hyaluronidase were investigated. Hyaluronidase was slightly activated by UVA alone. It was also activated by chlorpromazine, but the activation was enhanced by concomitant UVA irradiation. By pre-irradiation of chlorpromazine, it was found that a stable photoproduct of chlorpromazine was formed that activated hyaluronidase. As activation of hyaluronidase has been described in relation to tissue inflammation, the onset of chlorpromazine-induced photosensitivity may, in part, be related to the hyaluronidase activating effect of chlorpromazine plus UVA. PMID- 4022816 TI - Pre-PUVA UVA desensitization for solar urticaria. PMID- 4022817 TI - Photosensitive erythema multiforme apparently induced by phenylbutazone. PMID- 4022818 TI - Ocular findings in 340 long-term treated PUVA patients. PMID- 4022819 TI - Prenatal exclusion of xeroderma pigmentosum (XP-D) by amniotic cell analysis. PMID- 4022820 TI - Human cell transfection with skin cancer DNAs. AB - Spectacular progress towards understanding the molecular changes in DNA of many human tumors has been gained using NIH 3T3s as cellular recipients of transfecting DNA (1). Similar advances in analyzing human skin cancers have not been possible, as DNAs of most skin cancers or skin cancer cell lines--including most malignant melanomas--do not transform 3T3s (2). We have developed a DNA transfection system using human cells as recipients (3): normal human cells are transformed to anchorage-independent growth by transfection with a variety of skin cancer DNAs. This method may allow identification of the genes and specific sequences altered in sunlight-induced human skin cancers. PMID- 4022821 TI - Neuropsychology and behavior therapy. PMID- 4022822 TI - On the nature and measurement of agoraphobia. PMID- 4022823 TI - Behavior therapy and fire emergencies: conceptualization, assessment, and intervention. PMID- 4022824 TI - Behavioral pediatrics: research, treatment, recommendations. PMID- 4022825 TI - Progress in parent training. PMID- 4022826 TI - Symposium on self-destructive behavior. PMID- 4022827 TI - Suicide. A multidetermined act. AB - The act of suicide is usually multidetermined and involves individual, social, and psychiatric factors. This article presents case reports of a series of 13 manic-depressive patients who committed suicide. PMID- 4022828 TI - [Sedimentation leukapheresis in the treatment of resistant forms of lymphocytic leukemia]. PMID- 4022829 TI - [Early diagnosis of an abdominal form of non-Hodgkin lymphoma in children]. PMID- 4022830 TI - [Changes in the lungs and mediastinum in Hodgkin's disease]. PMID- 4022832 TI - [On the subject of medical philosophy: what is medicine today?]. PMID- 4022831 TI - [Malignant transformation of chondroblastoma--a case report]. PMID- 4022833 TI - [Usefulness of determining closing volume for evaluation of the functional state of the peripheral respiratory system in patients with chronic bronchitis]. PMID- 4022834 TI - [Functional evaluation of respiration before and after dialysis in patients with chronic uremia]. PMID- 4022835 TI - [Primary pulmonary hypertension with symptoms of portal hypertension]. PMID- 4022836 TI - Changes in atrial biopsies in chronic rheumatic heart disease. I: Cellulo vascular and mesenchymal reaction. AB - The cellular, vascular and connective tissue changes were studied in 32 atrial biopsy specimens from patients with chronic rheumatic heart disease (RHD). 15 of these 32 specimens showed some inflammatory reaction, 7 with small mononuclear cells only and 8 with macrophage reaction amidst increased but necrotic collagen, especially in the subepicardial and subendocardial regions. Most cellulonecrotic foci were histologically consistent with a stage of Aschoff nodule. Acid phosphatase activity in frozen sections was seen in the cytoplasm of the macrophages. Fine structural examination showed membrane-bound vacuoles and lipofuscin bodies rather than ingested material in the macrophages. By light and electronmicroscopy, these macrophages were not different from those encountered in other granulomatous or necrotic conditions. There was moderate proliferation of blood vessels, with prominence of endothelial cells and pinocytotic vesicles, or fibrosis of media, or proliferation of basal laminae. The presence of Aschoff nodules in the right atrium, the least affected chamber in RHD, suggests a diffuse and smouldering pathology on the basis of a persistent subclinical cell mediated immune (CMI) reaction. PMID- 4022837 TI - Changes in atrial biopsies in chronic rheumatic heart disease. II: Muscle fibre reaction. AB - Myocardial fibres were studied in the right atrial biopsies from 32 patients with chronic rheumatic heart disease (RHD). Paraffin and, particularly, araldite sections showed many muscle fibres well preserved, and others with large hyperchromatic nuclei, or with depleted myofibrils and increased mitochondria. With the SDH and ATPase reactions, there was no type difference in the myocardial fibres, and the former showed the reaction predominantly in the centre while the latter showed it mainly at the periphery of the fibres. At electronmicroscopy, fibres with intact myofibrils were found close to "degenerating" fibres with variable degrees of myofibrillar and myofilament disorganisation and loss, mitochondrial proliferation, occasionally with degeneration of cristae, and accumulation of lipofuscin in varying amounts, and irregularly tortuous or loosened intercellular junctions. This study has revealed more severe muscle changes than expected, even in the clinically less affected right atrial chamber in chronic RHD. It is speculated that this might be due to subclinical involvement of the tricuspid valve, known to be frequent in Indian patients, and the resulting "back pressure" on the right atrium might lead to changes in its myofibres. PMID- 4022838 TI - Ultrastructural changes of the human pancreas in acute shock. AB - Human pancreas tissue was studied electron microscopically during various stages of shock. The subcellular changes of exocrine pancreas affect in particular endoplasmic reticulum (ER), mitochondria, cytoplasm, and nuclei. Alterations correlate with duration and severity of shock, causing cell death in prolonged or severe manifestations of shock. This is obviously due to release of enzymes from zymogen granules; the ensuing damage cannot be distinguished from autodigestive pancreatitis. Lesions of exocrine pancreas cells are of multifactorial origin, arising from general shock-induced hypoxia, but also from local ischemia due to disturbed microcirculation provoking intravasal coagulation. Beyond these main causes, intracellular disorders of metabolism, obstruction of lymph drainage, and nervous factors may be of influence. As the cases surveyed in this paper had no fatal outcome - except for one patient - the changes described can be defined as non-lethal or as reversible. PMID- 4022839 TI - Nevus cells in axillary lymph nodes from radical mastectomy specimens. AB - From 1977 to 1983, 44 cases with nevus cells in the capsule and trabeculae of axillary lymph node specimens from about 7000 mastectomies performed for primary breast cancer were found. This finding was therefore less than 1%. In 3 cases, the nevus cells were present in 2 nodes, whereas in 41 cases solitary nodes were involved. In 13 cases, nevus cells were present in nodes that also contained metastatic carcinoma. Silver impregnation of reticulin fibers is very useful for the differential diagnosis of nodal metastases of breast carcinoma. PMID- 4022840 TI - Nuclear chromatin condensation of mouse lymphoma (L-1210) cells by methylnitrosourea. An electron microscopic and biochemical study. AB - When the mouse lymphoma (L-1210) cells are treated with methylnitrosourea (MNU) at 37 degrees C for 30 min and then cultured for 4 h in a normal medium nuclear structure and functions of the cells are changed. We have investigated the mechanism as to how nuclear structure and functions are changed by MNU. In MNU treated cells euchromatin area diminishes and chromatin condensation occurs. [3H]thymidine and [3H]uridine uptakes of the MNU-treated cells decrease. In contrast, when the MNU-treated cells are cultured in the presence of 3 aminobenzamide, a specific inhibitor of poly(ADP-ribose) synthetase changes of nuclear structure do not appear. [3H]Thymidine and [3H]uridine uptakes are partially and almost completely recovered, respectively. Autoradiographs of the cells labelled with [3H]NAD, a substrate of poly(ADP-ribose) synthetase show that silver grains due to [3H]ADP-ribose are densely located only in the cells where chromatin condensation occurs. Chromatin-bound proteins of molecular masses 20-25 X 10(3) daltons are specifically poly(ADP-ribosyl)ated in the MNU-treated cells. These results suggest that MNU-induced chromatin condensation is caused by poly(ADP-ribosyl)ation of chromatinbound proteins. PMID- 4022841 TI - Ischemic injury of the human pancreas. Its basic patterns correlated with the pancreatic microvasculature. AB - Based on the concept of the "primary lobule" as the microcirculatory unit of human pancreas that we previously established (Yaginuma et al., submitted to Path Res Pract), ischemic injuries of this organ were microscopically screened over many autopsy cases and were classified according to the zone of the unit involved. The primary lobule was defined as a small parenchymal region, supplied by a centrally placed arteriole and drained by flanking venules, often with an islet at the center because of its close relation with arteriole. The screening disclosed twenty out of 221 autopsy cases to be harboring some ischemic injury. In a 3-D reconstruction study performed on these pancreases to correlate the injured areas with performed architecture, three types of injuries were established as comprising different categories; 1) peripheral and 2) central necroses, both presenting as multiple small foci, the distribution of which in the former exactly coinciding with the central, and that in the latter with the peripheral zone of primary lobules, and 3) peripheral atrophy, uniformly affecting the peripheral acini. The first type tended to coexist with malignant hypertension, the second type was mostly found in shock cases and the third type exclusively in those with congestive heart failure. The pathogenesis of peripheral and central necroses was explained by a working hypothesis that correlates these categories with different impediments of microcirculation, assuming that in the former, blood flow was severely impeded by constriction of relatively proximal arteries, while in the latter, sporadic occlusion at terminal arterioles was responsible for peripheral ischemia. PMID- 4022842 TI - Pulmonary polymorphic centroblastic type malignant lymphoma in a patient with lymphomatoid granulomatosis, Sjogren syndrome and other manifestations of a dysimmune state. AB - A case of lymphomatoid granulomatosis arising in a patient with a long history of dysimmunity is reported. The autopsy reviewed the final evolution into a high grade malignant lymphoma with IgM K immunoglobulin production and discovered in deep lymph nodes modifications similar to angio-immunoblastic lymphadenopathy. PMID- 4022843 TI - A case of renal cell carcinoma solitarily metastasized to thyroid 20 years after the resection of primary tumor. AB - A case of renal cell carcinoma in a 69-year-old woman is reported. The woman developed a thyroid tumor recently. She has a history of nephrectomy done 20 years ago for a renal cell carcinoma. Based on the close resemblances of the histological features and cell nuclear DNA distributions of both tumors, the thyroid tumor was diagnosed as the secondary tumor from the renal cell carcinoma. In the review of the literature, this case of renal cell carcinoma seems to be that with the longest interval of years before solitary metastasis to the thyroid. PMID- 4022845 TI - Purveyors of cost-containment, beware. The buck stops here. PMID- 4022844 TI - Food, mind, and mood. Hyperactivity revisited. PMID- 4022846 TI - Evaluation of the patient with leg edema. AB - Leg edema is a common and challenging problem. The possible causes are numerous and are not limited to the vascular system. Bilateral swelling is usually a manifestation of systemic disorder, whereas unilateral swelling has many possible causes, the most common of which is chronic venous insufficiency. By means of the basic history and physical examination, a differential diagnosis can usually be established without extensive use of expensive diagnostic testing. PMID- 4022847 TI - Evaluation of the patient with intermittent claudication. AB - The most common cause of intermittent claudication is atherosclerotic occlusive arterial disease. Differentiation of the common musculoskeletal and neurologic conditions that may mimic intermittent claudication is often possible with a careful history, but when insufficient detail is provided or multiple conditions exist, the findings on physical examination and noninvasive studies are useful. While physical examination provides a rough estimate of the degree of ischemia, assessment of functional impairment produced by occlusive arterial disease is best made with noninvasive studies before and after standard exercise. Arteriography is reserved for the patient for whom restoration of pulsatile flow is planned. PMID- 4022848 TI - Evaluation of the patient with Raynaud's phenomenon. AB - Idiopathic Raynaud's phenomenon (Raynaud's disease) is very common among young women. A thorough history and physical examination are the keys to determining the extent of a diagnostic workup. In an otherwise normal and asymptomatic young woman with vasospastic attacks involving symmetric aspects of the digits, a CBC, urinalysis, chest film, and ESR are recommended as a cost-effective workup. If these studies are negative, the disease is probably benign. A history or physical findings consistent with collagen vascular disease, obstructive arterial disease, or carpal tunnel or thoracic outlet syndrome should lead to selected diagnostic tests. Men, persons with onset of vasospastic attacks after age 40, and those with severe disease or trophic changes of the digits deserve a more comprehensive workup to screen for underlying causes. PMID- 4022849 TI - Self-care. How to help patients share responsibility for their health. PMID- 4022850 TI - The family physician as psychotherapist. PMID- 4022851 TI - Aplastic anemia as complication of viral hepatitis. PMID- 4022852 TI - Legionella causing rhabdomyolysis and renal failure. PMID- 4022853 TI - Preparticipation evaluation of the adolescent athlete. Timing and content of the examination. AB - The aim of the preparticipation physical examination should be not only to uncover disqualifying conditions but also to screen for conditions that predispose to injury, to assess physical maturation, to determine physical fitness, and to educate the potential athlete regarding injury prevention and proper nutrition. By practicing these techniques, the physician can facilitate safe and healthful participation in organized sports by children and adolescents. PMID- 4022854 TI - Hyperventilation syndrome. Bridging the behavioral-organic gap. AB - Hyperventilation syndrome is frustrating to patient and physician alike. This common condition can be managed successfully if the primary care physician understands the pathophysiology of symptoms and takes a persistent, supportive approach to the patient. Invasive testing and psychiatric referral are less effective and more costly than an ongoing relationship with a primary care physician. Positive results are most likely to derive from frequent office visits marked by reassurance and repetition of instructions on how to cope with anxiety and its attendant symptoms. PMID- 4022855 TI - How to manage patient death and care for the bereaved. PMID- 4022856 TI - Smoking--the doctor's opportunity. PMID- 4022857 TI - Smoking and myocardial infarction: secondary prevention. AB - This prospective study examines the question 'Is it too late to stop smoking cigarettes once you have had a myocardial infarction?' One hundred and nineteen cigarette smokers (90 men, 29 women) who survived their first myocardial infarction for one month were followed for five years or until their death if earlier. The age corrected mortality rate of men who continued to smoke cigarettes was 2.2 times the age corrected mortality rate of those who stopped smoking after their infarct. The women who continued to smoke had 2.4 times the age corrected mortality of those who stopped smoking. The age and sex corrected mortality rates for the combined group of men and women show that those who stopped smoking after their infarction have 55% of the mortality of those who continued to smoke (P less than 0.05). These results suggest that smoking is not merely a 'risk factor' for myocardial infarction but is also a causal factor whose effects can be avoided by both men and women after an initial myocardial infarction. PMID- 4022858 TI - Pacemaker discomfort induced by the wearing of seat belts. AB - A survey was made of 100 consecutive pacemaker recipients to examine problems they may have experienced with seat belts whilst travelling by car, either as drivers (29 patients) or front seat passengers (50 patients). Twenty-one per cent of the drivers and 30% of the front seat passengers had experienced symptoms, usually of a mild nature. Re-siting of the generator was only necessary in 1 patient and no example of electrode displacement was observed. Suggestions are made as to how this problem might be overcome. PMID- 4022859 TI - Relationships between radiological and biochemical evidence of rickets in Asian schoolchildren. AB - One hundred Asian schoolchildren provided evidence of the relationships between radiological and biochemical evidence of rickets in a vitamin D-deficient population. In a retrospective study of the X-rays of 56 children the variables serum alkaline phosphatase, inorganic phosphorus and age provided a discriminant function which correctly classified 10 of 11 children with radiological evidence of rickets and 44 of 45 children with negative or marginally abnormal X-rays. When the discriminant function was applied to a prospective study of 44 children, three children with radiological evidence of rickets were correctly classified together with 38 of the remaining 41 children with negative or marginally abnormal X-rays. Serum alkaline phosphatase was the most important variable in the discriminant analysis, followed by serum inorganic phosphorus and age. Low levels of serum 25-hydroxy vitamin D (25-OHD) are of little value in predicting the severity of radiological evidence of rachitic bone disease in a vitamin D deficient population. PMID- 4022860 TI - Stones in the common bile duct: experience with medical dissolution therapy. AB - Thirty-one patients with radiolucent common bile duct stones received medical treatment. Nineteen had Rowachol, a terpene preparation, eight (42%) achieving complete stone disappearance within 3 to 48 months. Fifteen (including 3 of the above) took Rowachol with bile acid (chenodeoxycholic in 11, ursodeoxycholic in 4) for 3 to 60 months: 11 (73%) achieved complete dissolution within 18 months. Persistent symptoms and complications settled on conservative management: 8 (25%) patients required admission (2 biliary colic, 1 obstructive jaundice, 4 cholangitis, 1 pancreatitis). One patient died of a myocardial infarction during recovery from pancreatitis; the other continued treatment, 2 achieving complete dissolution/disappearance. Oral dissolution therapy with Rowachol and bile acids should be considered when endoscopic sphincterotomy or surgery is not feasible, but careful attention to potential complications is required while stones persist. PMID- 4022861 TI - Requests for hypnotic drugs and placebo response in elderly hospital in-patients. AB - Requests for night sedation and the use of placebo as first line drug management were studied prospectively in 1174 consecutive elderly hospital in-patients. Of the 390 (33.2%) patients requesting sleeping pills in hospital, 37 were subsequently satisfied without the prescription of additional medication. A further 216 patients were entirely satisfied with a placebo capsule during all of their hospital stay. An 'active' hypnotic drug was required by only 137 patients, many of whom were noisy and disturbing other patients in the ward. Most of the active hypnotic drugs prescribed to elderly hospital patients are unnecessary and a majority of those requesting hypnotics consistently respond to placebo. There remains a need for greater education of patients, nurses and doctors in the non pharmacological management of sleep disorders. PMID- 4022862 TI - Clinical evaluation of the Infrasonde D4000 blood pressure monitor. AB - Choosing a blood pressure machine from their ever increasing number is often difficult due to lack of performance data. We have evaluated a new automated non invasive blood pressure recorder, the Infrasonde D4000. In comparison with the Hawksley random zero mercury sphygmomanometer the Infrasonde showed less variability for both systolic and diastolic readings. However, it was found to record significantly lower mean systolic and diastolic pressures. PMID- 4022863 TI - Cerebral systemic lupus erythematosus presenting with catatonia. AB - A 13 year old girl with catatonia resulting from cerebral lupus is described. She had concurrent minor epileptic status, but abolition of her seizure activity failed to influence her catatonic state. She recovered after treatment with corticosteroids and immunosuppressive agents. Cerebral lupus should be considered in the differential diagnosis in patients presenting with catatonia. PMID- 4022864 TI - Atrial myxoma presenting with cerebral haemorrhage. AB - Emboli from left atrial myxomas are a recognized cause of cerebral ischaemia. The myxomatous embolus may infiltrate the cerebral arterial wall, resulting in aneurysmal dilatation with a risk of rupture. Myxoma-associated cerebral haemorrhage has been described in patients with progressive neurological dysfunction. We report a new presentation. Our patient, a previously healthy 20 year old girl, developed acute intracerebral haemorrhage for which craniotomy was performed. Histology of evacuated haematoma revealed an intravascular fragment of myxoma. Echocardiography demonstrated a left atrial myxoma which later was uneventfully excised. Early diagnosis of embolic cardiac myxoma requires awareness of the diversity of clinical manifestations, and careful histological analysis of surgical specimens. PMID- 4022865 TI - Ocular flutter in suspected multiple sclerosis: a presenting paroxysmal manifestation. AB - A patient with suspected multiple sclerosis is described who presented with attacks of blurring of vision and ocular flutter. This has not previously been reported as an isolated paroxysmal manifestation of brain stem demyelination. As with other paroxysmal disturbances ocular flutter may present as the first sign of the disease. PMID- 4022866 TI - Severe oesophageal injury caused by Steradent. AB - An elderly woman swallowed 2 tablets of a denture-cleansing agent (Steradent) believing them to be her sleeping tablets. This caused severe burning pain in the throat and resulted in a tight postcricoid oesophageal stricture. Treatment by repeated dilatation of the stricture has been only partially successful. Characteristic containers for non-medicinal tablets might help those with poor vision, and medicinal and non-medicinal tablets should never be stored in the same place. PMID- 4022867 TI - Tuberculosis of the thyroid gland associated with thyrotoxicosis. AB - Tuberculosis of the thyroid gland is rare. A case of tuberculosis of the thyroid gland associated with thyrotoxicosis is reported. PMID- 4022868 TI - Endomyocardial complications of the Churg-Strauss syndrome. AB - Although many similarities exist between the Churg-Strauss syndrome and the hypereosinophilic syndrome, these two disorders have hitherto been characterized by different types of cardiac disease. Two cases of the Churg-Strauss syndrome are described where the typical endomyocardial lesion of the hypereosinophilic syndrome dominated the clinical picture. PMID- 4022869 TI - Disseminated aspergillosis following radiation therapy for medulloblastoma. AB - A 16 year old girl who underwent surgery and radiotherapy for medulloblastoma is described. Shortly following the completion of treatment symptoms developed suggestive of tumour recurrence. At post mortem the cause was identified as disseminated aspergillosis with extensive cerebral involvement. The importance of this unusual complication is discussed. PMID- 4022870 TI - Oncogenic osteomalacia: strange tumours in strange places. AB - Two patients presented with hypophosphataemic osteomalacia and were subsequently found to have small tumours unusual histopathology and location causing the osteomalacia. Each tumour was found after an intensive search for occult masses. Studies of vitamin D metabolism and renal tubular function before and after surgery yielded further insight into the pathophysiology of oncogenic osteomalacia. These cases demonstrate that microscopic quantities of tumour are capable of causing the syndrome and further illustrate the high index of suspicion often necessary to locate causative tumours in patients with hypophosphataemic osteomalacia. PMID- 4022871 TI - Gonadal damage due to radioactive iodine (I131) treatment for thyroid carcinoma. AB - Papillary carcinoma of the thyroid is the most common type of thyroid cancer and is associated with a good prognosis. Complications of treatment with surgery and radioiodine are uncommon. We report the case of a 13 year old boy who developed testicular damage following treatment with radioactive iodine 350 mCi for a papillary carcinoma of the thyroid. Four years after radioiodine treatment there has been no suggestion of recovery of spermatogenesis. Detailed follow-up studies of similarly treated young patients are required to define the incidence of this complication and to determine its reversibility. PMID- 4022872 TI - Drug and non-thyroid induced changes in thyroid function tests. PMID- 4022873 TI - The prolonged QT interval--a frequently unrecognized abnormality. PMID- 4022874 TI - Increased plasma triglycerides, cholesterol and apolipoprotein E during prolonged fasting in normal subjects. AB - Plasma lipid and high density lipoprotein (HDL) levels were studied in 20 normal, healthy, non-obese males while fasting (150 kcal/d with free intake of water) for 6 d in a hunger strike. Plasma triglyceride and cholesterol levels were increased by 18% after 6 d of fasting. HDL-cholesterol concentration was not significantly changed for 4 d, but decreased by 22% after 6 d. Platelet aggregation induced by adenosine diphosphate (ADP) or collagen after 6 d of fasting was in the normal range. In 3 subjects fasted for 9 d, a complete plasma lipoprotein analysis was done. Very low and low density lipoprotein (VLDL and LDL) levels were elevated, whereas HDL was reduced after 9 d of fasting. On isoelectric focusing analysis, a marked reduction in apolipoprotein (apo) E concentration in both VLDL and HDL was noted. Liver function tests showed a reduction in hepatic enzyme activity; and since apo E is of hepatic origin also, we suggest that long fasting inhibits liver function in normal subjects. PMID- 4022875 TI - Low molecular weight measles immunoglobulin M in subacute sclerosing panencephalitis and acute measles. AB - Thirty eight patients with subacute sclerosing panencephalitis (SSPE) were investigated. Five patients who previously had measles immunoglobulin M (IgM) detected in unfractionated serum and cerebrospinal fluid (CSF) had measles IgM exclusively in the low molecular weight (LMW) fractions of serum and CSF. Measles IgM had previously not been found in unfractionated serum from 33 patients but was detected exclusively in the LMW fractions of serum from 30 patients. Seven children with acute measles had the expected high molecular weight (HMW) measles IgM in serum but 5 also had LMW measles IgM. Four young adults who had had measles in childhood had neither HMW nor LMW measles IgM in their sera. PMID- 4022876 TI - Chronic dyspepsia pain in general practice--its causes and diagnosis. AB - One hundred consecutive patients who had consulted their general practitioner because of upper abdominal pain related to eating, were investigated after initial interviews by the general practitioner, a medical registrar and the same consultant physician. Thirty seven had active upper gastrointestinal or biliary tract diseases, including 29 with peptic ulcers. The general practitioner and consultant correctly distinguished between organic and non-organic dyspepsia (NOD) in 51 and 65 cases respectively. Although the sensitivity of the general practitioner diagnosis of organic disease was high (95%), the specificity (23%) and predictive value (42%) were low. There were fewer organic diagnoses amongst the patients under the age of 30 (P less than 0.05) and those with symptoms for less than 3 months (P less than 0.01). No patient under 30 with symptoms for less than 3 months had organic dyspepsia. We suggest that if dyspeptic patients over the age of 30 and those under 30 with symptoms for longer than 3 months are investigated, about one-third will be found to have organic diseases. PMID- 4022877 TI - Ventricular tachycardia precipitated by sodium iothalamate (Conray 420) injection during prenylamine treatment: a predictable adverse drug interaction. AB - A case of ventricular tachycardia occurring after intravenous injection of sodium iothalamate (Conray 420) into a patient taking prenylamine is described. Both of these drugs may cause prolongation of the corrected QT interval and the mechanisms of this potentially fatal drug interaction are discussed. PMID- 4022878 TI - Ventricular arrhythmias complicating weight reduction therapy in a patient with a prolonged QT interval. AB - Serious ventricular arrhythmias are known to occur in patients with long QT intervals. We describe a case of torsade de pointes occurring in a patient with a prolonged QT interval while taking a 1000 calorie diet, diethylpropion hydrochloride (Tenuate Dospan) and bendrofluazide. In patients with long QT intervals, hypokalaemia and drugs which further delay repolarization may facilitate the development of life threatening arrhythmias. PMID- 4022879 TI - Painful dysphagia in a case of mediastinal tuberculous lymphadenopathy. AB - A patient with mediastinal tuberculous lymphadenopathy is described. Presentation was with rapid onset of painful dysphagia following trauma to the neck. Early diagnosis was achieved by mediastinoscopy. PMID- 4022880 TI - Adrenal insufficiency and bilateral adrenal enlargement: demonstration by computed tomography. AB - A patient presented with fever, malaise and a staphylococcal wound infection occurring 3 weeks after severe haemorrhage from a lacerated brachial artery. There were no clinical features to suggest Addison's disease but abdominal computed tomography to exclude abdominal sepsis showed bilateral adrenal gland enlargement with preservation of adrenal shape. This was consistent with resolving adrenal haemorrhage or infarction and endocrinological investigations confirmed primary adrenal failure. PMID- 4022881 TI - Familial bilateral multiple fibroadenomas of the breast. AB - This paper describes multiple breast fibroadenomas in three siblings. It appears that the familial disorder seen is associated with bilateral multiple fibroadenomas. PMID- 4022882 TI - Female type cystic hyperplasia in a male breast. AB - A 28 year old man had a swelling of the right breast. He was phenotypically and karyotypically a normal male. Microscopic examination of the excised specimen showed the pattern of cystic hyperplasia identical to that commonly seen in the female breast. Numerous cysts were grouped in a lobular pattern and their lining showed apocrine metaplasia. There was extensive background fibrosis, some mammary duct ectasia and some features consistent with the more classical microscopic appearances of gynaecomastia. Whilst some of the features noted above are sometimes seen in gynaecomastia the presence of the full range of the features of cystic hyperplasia is distinctly unusual in the male. PMID- 4022883 TI - Trigeminal trophic syndrome. AB - Two cases of ulceration of the face following surgical sensory denervation are described. Both patients presented to a geriatric unit because of problems associated with mental impairment. There are relatively few reports of similar ulcers. A review of the literature suggests that mental impairment is an important aetiological factor. PMID- 4022884 TI - Placental chorioangiomatosis--a high risk pregnancy. AB - A case of diffuse chorioangiomatosis leading to fetal hydrops, disseminated intravascular coagulopathy with massive umbilical vein thrombosis and fetal death is described. Although rare, this benign mesenchymatous malformation of the placenta should be kept in mind as a possible cause of neonatal morbidity. Prenatal diagnosis could prevent fetal death. PMID- 4022885 TI - Ergotamine abuse and extra-hepatic portal hypertension. AB - Arterial complications following ergotamine therapy have been well recognized since the beginning of this century. Venous complications, however, have only rarely been reported. A 48 year old Nigerian woman developed extra-hepatic portal hypertension coincident with a chronic overdosage of ergotamine. The literature elucidating the possible mechanisms involved is reviewed. PMID- 4022886 TI - Reversible renal failure due to psychogenic urinary retention. AB - A case of advanced, reversible renal failure due to psychogenic urinary retention occurring in a 17 year old female, is reported. The diagnosis of psychogenic urinary retention was made on the basis of existent florid psychopathology and the concomitant exclusion of an organic cause. Family psychodynamics are discussed. Psychosocial intervention led to a resumption of normal micturition, the disappearance of the urinary retention with resultant improvement of renal function. PMID- 4022887 TI - Gallstone perforation of the ileum without obstruction. PMID- 4022888 TI - Failure of acetazolamide to prevent acute mountain sickness. PMID- 4022889 TI - Lowered ultraviolet minimal erythema dose in hemiplegia. AB - In view of recent reports of increased tanning in hemiplegic limbs, we have investigated ultraviolet (u.v.) minimal erythema dose (MED) in hemiplegia using the bilateral comparison technique. Seven of 10 patients had a lower MED in the hemiplegic arm compared to the normal side, the mean reduction being 16% (range 0 33%, P = 0.003). No patients had a higher MED in the hemiplegic arm. We review the literature regarding other non-neurological features of hemiplegia, in particular asymmetry of temperature, oedema, and finger clubbing, and we propose a vasomotor or trophic aetiology for these findings. PMID- 4022890 TI - Subconjunctival haemorrhage: a feature of acute severe asthma. AB - Bilateral subconjunctival haemorrhage was observed on 5 separate occasions in 4 patients presenting a fulminant form of acute severe asthma. Four of these episodes required ventilatory support. All patients recovered from their asthma attack after treatment with bronchodilators, corticosteroids, and oxygen. The incidence of this previously unreported finding represents 5% of the total number of patients with acute severe asthma mechanically ventilated in our intensive care unit from 1976. PMID- 4022891 TI - Nonspecific small bowel ulceration. AB - Six patients (4 male, 2 female) developed nonspecific small bowel ulceration between the ages of 4 months and 76 y. Five had gastrointestinal haemorrhage, usually chronic and resulting in iron deficiency anaemia. Four had features of subacute intestinal obstruction; there were no perforations. A small bowel enema was the most useful single investigation for delineating the lesions, and surgical excision was curative in all but one case. No aetiological causes could be implicated, other than in one patient taking a daily tablet of Navidrex-K. PMID- 4022893 TI - Reversible coma in Wernicke's encephalopathy. AB - A case of coma due to Wernicke's encephalopathy complicated by respiratory failure is described. Ventilation and thiamine administration lead to recovery, although Korsakoff's psychosis and ataxia persisted. A review of similar cases of coma emphasizes the absence of diagnostic features, but that if structural disease is excluded the presence of pupillary and ocular signs may support a diagnosis of Wernicke's encephalopathy. The response to thiamine may be diagnostic as in 8 of these patients who received it, but the long-term morbidity remains high. PMID- 4022892 TI - Serum creatine kinase after intramuscular injections. AB - Serum creatine kinase (CK) activity was measured after intramuscular injections in 44 patients hospitalized for non-cardiac reasons. The drugs injected were: diazepam, dipyrone, metoclopramide, meperidine, pentazocine and procaine penicillin. Only 3 out of 44 patients (7%) demonstrated significant elevation of CK levels following the intramuscular injections. In these 3 patients the elevation was mainly due to a rise of the MM-isoenzyme fraction with MB levels increased in one patient. These findings do not justify the common clinical notion of regarding intramuscular injections as a frequent cause of serum CK elevation. It is concluded that high CK serum values in a patient with chest pain should always be considered with utmost suspicion, disregarding the possible effects of a previous intramuscular injection. PMID- 4022894 TI - Disordered oesophageal motility in thyrotoxic myopathy. AB - Dysphagia is an uncommon feature of thyrotoxic myopathy, and is usually associated with other signs of bulbar weakness, such as dysarthria and nasal regurgitation. We report a case of thyrotoxicosis presenting with dysphagia due to diminished oesophageal motility associated with significant hypercalcaemia; both abnormalities resolved rapidly following treatment. PMID- 4022895 TI - Avulsion of the anterior superior iliac spine complicating bone biopsy. AB - We present a case report of avulsion of the anterior superior spine following a transiliac crest biopsy, a previously unreported occurrence. PMID- 4022896 TI - Post partum presentation of hypercalcaemic sarcoidosis. AB - A number of corticosteroid responsive diseases have been shown to undergo exacerbation in the puerperium. The presentation of a woman 8 weeks after delivery with severe hypercalcaemia, a highly steroid sensitive feature of sarcoidosis, adds to the evidence that sarcoidosis can also be numbered amongst such diseases with relapse in the puerperium. PMID- 4022897 TI - Sudden death due to isolated adrenal tuberculosis. AB - A 65 year old man admitted to hospital for investigation of pleural thickening was found to have carcinoma of the prostate with metastases. Before investigations were completed the patient collapsed unexpectedly with hypotension. A post mortem examination revealed tuberculosis of both adrenal glands without evidence of tuberculosis in any other organ. PMID- 4022898 TI - Addison's disease due to metastases to the adrenal glands. AB - A 43 year old patient with Addison's disease secondary to extensive metastases to both adrenal glands is presented. Thirty two previously reported cases are reviewed; in only 13 cases was the diagnosis of Addison's disease confirmed biochemically. Reasons for the apparent rarity of Addison's disease in spite of the frequency of adrenal metastases are discussed. The need to consider the possibility of Addison's disease complicating known malignant disease arising in other tissues is stressed. PMID- 4022899 TI - Congenital hepatic fibrosis and adult-type autosomal dominant polycystic kidney disease in a child. AB - This reports a family with congenital hepatic fibrosis and adult polycystic kidney disease. Adult polycystic kidney disease was present in three generations. In addition, congenital hepatic fibrosis occurred in two members of the third generation. These conditions are generally held to have different modes of inheritance and the significance of their occurrence together is not clear. PMID- 4022900 TI - Nitrous oxide as an opioid and the association between the therapeutic use of narcotics and addiction. PMID- 4022901 TI - Evaluation of simultaneous selection for live body weight and against abdominal fat in broilers. AB - Three hundred chickens from pedigree matings in a commercial female grandparent stock were slaughtered at 7 or 9 weeks of age. Data were obtained for live body weight and various carcass parts. Coefficients of variation of abdominal fat (g and g/100 g body weight) were above 30%. Coefficients of variation of the weights of muscular and skeletal parts were much lower (about 10%) and were further reduced when calculated per 100 g body weight. Heritability of abdominal fat was higher (.82) than that of live body weight (.55) and parts: breast (.55), thighs (.31), and drumsticks (.51). Phenotypic and genetic correlations between each of the heavier parts (breast, thighs, and drumsticks) and body weight were over .8; for smaller parts (legs, wings, etc.) correlations (.49 to .79) were lower. Abdominal fat showed the lowest correlation (.26 to .36) with body weight. The genetic correlations seemed free of the part-whole relationship. Simultaneous selections for live body weight and for breast weight, or against abdominal fat, were simulated using "independent culling levels". The theoretical calculations showed that adding breast weight as a selection criterion had no advantage over selection for body weight alone due to the high genetic correlation between the two traits. However, simultaneous selection for body weight and against abdominal fat, using optimum combination of culling, was economically superior to selection for body weight alone. The advantage of this two-trait selection depends on the correlation between the traits and their relative values. PMID- 4022902 TI - The influence of dietary salt on water consumption and carcass lipids in Japanese quail. AB - Studies were conducted to investigate the influence of dietary salt on water consumption and subsequent carcass lipids in Japanese quail at various ages. In Experiment 1, randombred nongrowth-selected (C) quail were fed 28% protein diets containing .0, .4, .8, 1.6, and 3.2% added salt. In Experiment 2, growth-selected P- and C-line quail were fed 20%-protein diets containing .4% and 3.2% added salt. The different dietary salt levels did not exert a consistent effect on body weight in Experiment 1. There was no adverse effect of salt level on feed consumption and efficiency and no direct effect on abdominal fat or carcass lipid levels. High salt (1.6 and 3.2%) stimulated water consumption and increased water:feed ratios. Water:feed ratios were higher for quail than for broilers, suggesting a species difference. In Experiment 2, C-line quail demonstrated similar effects to the high-salt (3.2%) diet in Experiment 1. High salt (3.2%) adversely affected body weight, feed consumption, abdominal fat, and carcass lipid in P-line quail. There was no affect on feed efficiency, and a substantial stimulation of water consumption with concomitantly increased water:feed ratios. The relatively low abdominal fat observed at 4 weeks of age indicate that nongrowth-selected quail may not be a good model for the study of abdominal fat in broilers. PMID- 4022903 TI - The delayed and saline wattle reactions in broilers challenged with bovine serum albumin. AB - Bovine serum albumin was used to study the development of a wattle reaction in broiler-type chickens. A strong response developed in both nonsensitized and sensitized chickens and the frequency of such was shown to be dependent on the method used for the sensitization. A similar swelling developed in a proportion of the wattles injected with saline and this too seemed to be influenced by the sensitization method. Moreover, both types of responses were shown to be somewhat unstable during the first 24 hr postchallenge. PMID- 4022904 TI - Influence of supplemental ascorbic acid on broiler performance following exposure to high environmental temperature. AB - The present study was conducted to determine if dietary ascorbic acid (AA) would improve growth, feed efficiency, and livability of broilers following an acute heating episode. Supplemental AA was provided in the diets at calculated levels of 0, 250, 500, and 1000 ppm, continuously. Females that received 1000 ppm exhibited significantly greater body weights at 2 and 4 weeks of age. No significant effects due to AA supplementation were observed in body weights of males. At 4 weeks of age, chicks were heated on two consecutive days by increasing the ambient temperature (38.3 C at bird level) in the production facility. Heating significantly reduced body weights in males, but not females, at 5 and 7 weeks of age. Feed conversions were increased after heating, but significant effects due to AA were not found. Ascorbic acid did not improve overall livability significantly in either sex, but heat-associated mortality was reduced in supplemented females. PMID- 4022906 TI - Serum proteins of three turkey strains under different seasonal conditions. AB - Total serum protein and serum protein fractions of three local turkey strains (White, Red, and Black) were measured under different seasonal conditions. Total serum protein was influenced (P less than .05) by strain (6.00, 6.15, and 6.28 g/100 ml for White, Red, and Black, respectively) and sex (6.02 and 6.26 g/100 ml for males and females, respectively). Highest levels were recorded under moderate seasonal conditions and lowest under high temperature and low humidity. The interactions of strain X sex and sex X season were not significant (P greater than .05), whereas strain X season was significant (P less than .05). Highest levels of albumin were encountered in Black and Red strains. Sex and season did not exert significant effects (P greater than .05); only the interaction of strain X season was significant (P less than .05). Strain had a significant effect on alpha-1 but not on alpha-2, beta-, and gamma-globulins, whereas sex was a source of variation in all globulins (P less than .05). Season induced significant (P less than .05) variation in globulins. Maximal levels were observed under moderate temperature and relative humidity. Strain X season and strain X sex interactions were not significant with regard to alpha-1 values. Similar trends were observed in beta-globulins for strain X sex and season X sex interactions (P greater than .05). PMID- 4022905 TI - Development of a basal diet to study broiler chicken responses to the sulfur containing amino acids and sodium sulfate. AB - Three experiments were conducted to develop a basal diet limiting in the sulfur containing amino acids and with adequate sodium. Twelve hundred commercial male broiler chicks were grown to 3 weeks of age in battery brooders. Chicks were fed a diet of a corn-soybean meal-poultry oil containing .38% methionine, .74% total sulfur-containing amino acids, and .10% sodium. The first two experiments, pooled for statistical analyses, showed that supplementation with .25% L-methionine significantly increased chick growth over the basal (496 vs. 465 g; P = .034) as did sodium supplementation (518 vs. 465 g; P less than .001). The best growth rate occurred when L-methionine and sodium chloride (NaCl) were supplemented together at .25 and .33%, respectively (579 g gained). The response from NaCl was demonstrated to be due to the sodium and not the chlorine by comparison to responses from potassium chloride (KCl) and sodium carbonate (Na2CO3) supplementation. It is suggested that two "first-limiting" nutrients, methionine and sodium, exist for chicks fed this particular diet. In Experiment 3, a response surface was determined with supplemental sodium (as NaCl) and L methionine each varying from 0 to .20% (.10 to .30% total sodium and .38 to .58% total methionine). It was concluded that .20% total sodium is adequate to maximize growth and feed efficiency (.20% better than .13%, no different from .27%). Similarly, .17% supplemental methionine (.55% total) appears to be adequate (.17% better than .10%; .20% not better than .17%) with no supplemental choline. PMID- 4022908 TI - The mechanism of the ejection of a frothy fluid from the cloaca in the male turkey. AB - The mechanism of the ejection of a frothy fluid from the "tissue at the vicinity of the papilla" (TVP) of the ductus deferens and triangular fold (TF) of the cloaca of the male turkey during natural copulation was investigated. Injection of Evans blue (T-1824) solution into the wing vein of the intact male led to the ejection, immediately after injection, of frothy fluid colored blue. Ligation of the A. pudenda interna decreased the volume of fluid to a negligible amount, and removal of the paracloacal vascular body (Corpus vasculare paracloacale) completely suppressed the tumescence of the copulatory organ and the flow of the fluid (lymph-like fluid). Evans blue solution, introduced into the A. pudenda interna of dissected cloacal specimens, exuded out from the TVP but not from the lymphatic folds (plicae lymphaticae). Injection of dye solution into the paracloacal vascular body elicited only the erection of the phallus, and none flowed out from the surface of the lymphatic folds. Also, no ejection of the injected dye solution into the A. pudenda interna was found in the dorsal wall of the cloaca, particularly from the TF. The results suggest that lymph generated in the paracloacal vascular body caused only the tumescence of the copulatory organ and a lymph generated in the TVP exuded through the surface epithelium. In addition, a foam (froth) is produced in the TF of the middorsal proctodeum during mounting behavior which appears to be added to the aforementioned lymph from the TVP at copulation. PMID- 4022907 TI - Fatty acid compositions of triacylglycerols and phospholipids in hen liver lipid before and after sexual maturity. AB - Changes in fatty acid composition of triacylglycerols and phospholipids of the hen liver lipid on coming into egg production were described. Of the major fatty acids of triacylglycerols, a high content of oleate and low content of stearate and polyenoic acids were observed in the hen liver at all ages (97 to 167 days of age). In contrast, high stearate and polyenoic acids were present in the liver phospholipids at all ages. The oleate content in triacylglycerols was twice that of phospholipids. Triacylglycerols of the hen liver were more unsaturated than phospholipids throughout the experiment. The triacylglycerols of the control and estrogenized male chicks were also more unsaturated than the phospholipids. The distribution patterns of carbon-18 fatty acids (stearate, oleate, and linoleate) of triacylglycerols and phospholipids in liver lipid were examined. Both females and males showed similar distribution patterns of carbon-18 fatty acids of the triacylglycerols. In the phospholipids, all birds also showed similar distribution patterns, but these patterns were distinctly different from those of the triacylglycerols. PMID- 4022909 TI - Phosphorous requirements of laying hens in a semiarid continental climate. AB - Single Comb White Leghorn layers raised in floor pens in conventional open housing were used to determine their phosphorous requirement in a semiarid continental climate. Dietary available phosphorous (AP) of .15, .25, .35, and .45% were fed continuously from 26 to 74 weeks of age. Concurrently, diets containing .45, .35, and .25% AP or .35, .25, and .15% AP were "phase fed" during the age intervals of 26 to 42, 42 to 54, and 54 to 74 weeks, respectively. Diets used were corn-soybean diets in which the phosphorous was varied by changing the level of dicalcium phosphate in the ration. Under the conditions of this experiment, hens required a minimum of .25% AP for best egg production, feed consumption, and body weight gain. The AP levels above .35% depressed shell thickness. In a phase-feeding program, when the last phase corresponds with the summer season, AP should not go below .25% for best performance. PMID- 4022910 TI - Fertility of fresh and stored turkey spermatozoa in the presence or absence of glucose or fructose in the suspension medium. AB - Turkey hens were inseminated with either fresh or stored (4 hr at 15 C) semen suspended in a sugar-free medium or one containing 15 mM glucose or fructose. Rates of fertilization of eggs collected for 15 days after insemination were not affected by the presence or absence of glucose or fructose in the medium nor by storage. PMID- 4022911 TI - Whole brain acetylcholinesterase activity in lead-exposed Japanese quail. AB - A study was conducted in which male and female Japanese quail were fed dietary lead as lead acetate from hatch through 12 weeks of age. Lead was added to the diet at 0, 1, 10, 100, and 1000 mg/kg feed. Significant reductions in whole brain acetylcholinesterase (AChE) activity were found at all treatment levels. Additionally, a sexual dimorphism in brain weight and AChE activity was found. Breeding males had heavier brain weights and lower AChE activity than females. Brain weight was not affected by lead treatment. However, females exhibited a greater lead-induced decrease in AChE activity. PMID- 4022912 TI - Relationship of body fat to fertility in broiler breeder hens. AB - Sixty-one dwarf broiler breeder hens (58 weeks of age) were utilized to examine relationships among body weight, body fat, oviduct fat, and fertility. Body weight showed a significant (P less than .05) positive relationship to percent body fat (r = +.26). The correlation coefficient between percent body fat and percent oviduct fat was +.26 (P less than .05). Body weight and percent body fat were negatively correlated with fertility; oviduct fat, however, was not significantly correlated to fertility. The adverse effect of body fat on fertility seems to involve a mechanism other than increased fat deposition in the oviduct. PMID- 4022913 TI - Heritability of live and abdominal fat weights in Coturnix quail. AB - Twenty-seven single-pair matings of Coturnix quail produced 48 sons and 50 daughters. Parents and progeny were reared under similar conditions and killed at 58 days of age. Live and abdominal fat weights were obtained. Heritability estimates from parent-offspring regressions ranged from .05 to .72 (live weight), .49 to .80 (abdominal fat weight), and .45 to .88 (percent abdominal fat/live weight). The high heritabilities for live weight (except sire-daughter regression) and for abdominal fat in Coturnix quail indicate that a selection method could be used to reduce fat and increase live weight. PMID- 4022914 TI - Effect of citric and ascorbic acids on performance and intestinal pH of chicks. AB - An experiment was conducted to investigate the effect of one percent dietary citric and ascorbic acid additions on performance and intestinal pH of young chicks. The citric and ascorbic acid additions did not affect chick performance or pH of the duodenal lumen contents. Also, pH of the duodenal lumen contents was not affected by 1:2 to 1:8 dilutions with distilled water. PMID- 4022916 TI - Abstracts of papers. Sixth annual meeting of the Southern Poultry Science Society. January 22-23, 1985, Atlanta, Georgia. PMID- 4022917 TI - Abstracts of papers to be presented at the 74th annual meeting of the Poultry Science Association, Inc. PMID- 4022915 TI - Relationship between activity at a young age and feed efficiency in chickens. AB - Feed conversions of three Ottawa strains of Leghorns were measured from hatch to 27 days and bird activity at 1, 2, and 4 weeks of age was assessed. Males were more active than females. Chicks of the more active strain consumed more feed and had poorer conversion than those from the least active strain. Ranking of the strains on feed conversion to 27 days was similar to their ranking on feed consumed per egg mass produced in an earlier study. PMID- 4022918 TI - Occupational health and the general practitioner. PMID- 4022919 TI - Building sickness. PMID- 4022920 TI - Visual display units and health. PMID- 4022921 TI - Stress at work. PMID- 4022922 TI - Unemployment and health during a recession. PMID- 4022923 TI - The offshore worker. PMID- 4022924 TI - Myocardial infarction and advice on sexual activity. PMID- 4022925 TI - The results of hand surgery in rheumatoid arthritis. PMID- 4022926 TI - Hypnotherapy--a useful tool in general practice. PMID- 4022927 TI - [Lung embolism: etiology, pathophysiology, clinical aspects and therapy]. PMID- 4022929 TI - [Differences in lung function in smokers, former smokers and nonsmokers]. PMID- 4022928 TI - [Improvement of ventilation in patients with restrictive and irreversible obstructive ventilation disorders by a single dose of theophylline]. PMID- 4022930 TI - [Diagnosis, course and treatment of a case of veno-occlusive disease]. PMID- 4022931 TI - [Results of a serum concentration-oriented dosage of a theophylline depot preparation in ambulatory patients with chronic obstructive lung disease]. PMID- 4022932 TI - [Combined use of an inhalation antigen test and bronchoalveolar lavage in the diagnosis of extrinsic allergic alveolitis]. PMID- 4022933 TI - [Recurring, menstruation-dependent spontaneous pneumothorax--successful treatment with chemical pleurodesis]. PMID- 4022934 TI - [Speech and intelligence performance in relation to social class and family status]. PMID- 4022935 TI - [Inpatient adolescent psychiatric therapy as evaluated by the patients]. PMID- 4022936 TI - [A "mimickry" patient: report on attempted treatment of a self-inflicted disease]. PMID- 4022937 TI - [Group processes in team supervision--constructive and destructive effects]. PMID- 4022938 TI - [Psychologic problems in children and adolescents in orthodontics]. PMID- 4022939 TI - [Dreams in the treatment of children and adolescents with preoedipal disorders]. PMID- 4022940 TI - Five cases of prenatally diagnosed sex chromosome mosaicism. AB - Prenatal detection of chromosome mosaicism is a relatively rare phenomenon and always constitutes a diagnostic problem. The difficulties are much more when the mosaics involve the sex chromosomes, because of the large phenotypic variability in individuals with these abnormalities. We studied 5 cases of true mosaics, 4 of these were prenatally detected, while 1 case was revealed only in the fetal lymphocytes after induced abortion. The limits of amniotic fluid culture with regard to the diagnosis of true mosaics and the difficulties arising in genetic counselling are discussed. PMID- 4022941 TI - Testosterone levels in midtrimester maternal and fetal plasma and amniotic fluid. AB - Testosterone was measured in maternal plasma (58 samples), amniotic fluid (71 samples) and fetal plasma (55 samples) in 79 patients between 15 and 23 weeks' gestation. Maternal plasma testosterone levels were unrelated to fetal sex. Amniotic fluid testosterone was significantly higher in male than female fetuses but did not reliably predict fetal sex. A correct diagnosis of fetal sex was made by testosterone assay of pure fetal plasma in 39 out of 40 males and in 15 out of 15 females using 1.70 nmol/l as the cut-off value. This investigation is not the method of choice for routine fetal sexing but may be of value in fetuses suspected of having certain endocrine disorders. PMID- 4022942 TI - Temporal changes in the utilization of amniocentesis for prenatal diagnosis by women of advanced maternal age, 1976-1983. AB - Utilization of amniocentesis for prenatal diagnosis because of the indication of advanced maternal age (greater than or equal to 35 years at delivery) was examined in the population of B.C. over an 8-year period (1976-1983). As of 1983, approximately one out of three eligible women (greater than or equal to 35 years at delivery) is having the test. In the older group (greater than or equal to 38 years at delivery) approximately one out of two eligible women is having the test. The data do not indicate that the proportion of eligible women having amniocentesis has reached a plateau; utilization is continuing to increase. It appears that prenatal diagnosis is an ethically acceptable alternative for a large proportion of the population. PMID- 4022943 TI - Prenatal diagnosis of trisomy 10 p in a twin pregnancy. AB - A twin pregnancy with trisomy 10 p due to a paternal 10;12 translocation is reported. The prenatal diagnosis steps followed in twin pregnancies are reviewed and the concordant features of trisomy 10 p seen in both fetuses confirm previous reports on the clinical features of this chromosomal defect. PMID- 4022944 TI - Prenatal diagnosis of the fragile-X in male monozygotic twins: discordant expression of the fragile site in amniocytes. AB - A prenatal diagnosis of the fragile-X syndrome in monozygotic male twins is reported. The expression of the fragile site was discordant in amniotic cells. Fetal blood and, after therapeutic abortion, skin fibroblasts were positive in both fetuses. Our data suggest that great care should be taken when using amniocytes for prenatal diagnosis of the fragile-X syndrome. PMID- 4022945 TI - Therapeutic abortion following midtrimester amniocentesis. PMID- 4022946 TI - Cellular growth of the placenta in twin pregnancy late in gestation. AB - In order to establish the pattern of cellular growth in placentae from human twin pregnancy, the total placental concentrations of deoxyribonucleic acid (DNA) and protein were determined. Twin placentae from 31 to 40 weeks' gestation were analysed from 40 pregnancies whose precise gestational ages were known. The study has shown that nuclear multiplication continues until placental growth in weight itself comes to an end. Increase in placental weight was caused by cellular hyperplasia without hypertrophy. PMID- 4022947 TI - Physiological aspects of placental ontogeny and phylogeny. PMID- 4022948 TI - Morphological aspects of placental ontogeny and phylogeny. PMID- 4022949 TI - Hydatidiform mole in Nottingham: a 12-year retrospective epidemiological and morphological study. AB - The results of a 12-year retrospective study on the epidemiology of hydatidiform mole (HM) in Nottingham are presented. We have reviewed the histology of our cases of HM, tried to minimize selection bias, and have used the most reliable data available. Using data from two different sources we have calculated the frequency of HM as 1 in 1400 deliveries. The frequency of HM in this study is one quarter of that reported in an excellent study from Japan. We suggest that, with accurate epidemiological studies, the difference in frequency of HM between 'high risk' and 'low risk' areas is less than previously accepted. The present study also shows a lower incidence of persistent trophoblastic disease than previously generally accepted. We confirm that partial HM is a distinct clinicopathological entity and that two forms are distinguishable histologically. The malignant potential of partial HM is uncertain, and we suggest that the clinical management of partial HM should be no different from that of complete HM until further studies dictate otherwise. PMID- 4022950 TI - Human placental mitochondrial respiration and its regulation by adenine nucleotides. AB - Respiratory parameters were studied in mitochondria from human placenta. Respiratory control and ADP/O ratios were low in this preparation. The adenine nucleotide content of placental mitochondria was found to be only one quarter of that found for adult uterine muscle tissue mitochondria prepared in the same way. Loading placental mitochondria with adenine nucleotides by incubation in the presence of ATP produced increased respiratory control ratios but no improvement in ADP/O ratios. Our evidence is consistent with the developmental changes shown to occur in rat liver, in which an increased concentration of adenine nucleotides is responsible for changes in respiratory parameters. PMID- 4022951 TI - Morphometric studies of fetal placental stem arteries in hypertensive disorders ('toxaemia') of pregnancy. AB - The mural thickness of fetal stem arteries of 3rd order was assessed morphometrically in 50 placentae from each of the 'toxaemia', normal pregnancy and acute fetal distress groups. Several clinical maternal and fetal variables and the syncytial sprout proliferation of the placentae were correlated with the morphometric findings. The results show that: (1) there was a significant reduction in the ratio of lumen-to-whole-diameter of the fetal arteries in 'toxaemia' as compared with the two other groups; (2) the mean lumen-to-whole diameter ratio also differed between regions of the placenta in all groups, the most marked reduction being in the parachorial region and the least prominent in the parabasal zone; (3) no significant differences in the mean diameter ratio were found among the three sub-groups of the toxaemic pregnancies, i.e., the preeclampsia, essential hypertension and renal disease group; and (4) there was an inverse relationship between the lumen-to-whole-diameter ratios and the syncytial sprout counts in the toxaemic group. PMID- 4022952 TI - A description of human placental syncytiotrophoblast membrane glycosphingolipids. AB - The glycosphingolipid (GSL) structure of isolated human term placental syncytiotrophoblast microvillous plasma membrane (StMPM) has been investigated by Folch solvent extraction and thin-layer chromatography. StMPM preparations were shown to contain unique hydrophilic GSL species, including two highly glycosylated (greater than 15 saccharide residues/molecule) components. This fraction consistently included four major gangliosides (sialylated GSL), as well as two highly-sialylated (greater than or equal to 4 sialic acid residues/molecule) minor gangliosides. PMID- 4022953 TI - Stereological studies on the true thickness of the villous membrane in human term placentae: a study of placentae from high-altitude pregnancies. AB - Stereological principles were used to calculate functionally significant dimensions of the human villous membrane, its arithmetic mean thickness (Ta) and its harmonic mean thickness (Th). The former is proportional to tissue mass and oxygen consumption, the latter to diffusional resistance. For a group of 15 term placentae from uncomplicated pregnancies at high altitude, the average values were Ta = 4.44 micron, Th = 3.56 micron and Ta/Th = 1.26. The latter figure provides a useful quantitative expression for the efficiency of the membrane in gas and metabolite diffusion. It implies that vasculosyncytial membranes and syncytial knots decrease resistance to diffusion by 26 per cent, compared with that of a membrane with uniform thickness throughout. The methods are simple to apply and provide better estimates of true thickness than do measurements confined to thin sections. PMID- 4022954 TI - Extracellular binding of calcium in the guinea-pig placenta. AB - Extraction of 45Ca from the perfused umbilical vascular bed of the guinea-pig placenta was measured using 3H-sucrose or 24Na as reference substances at a constant inflow concentration of the tracers. La3+ (5mM) depressed extraction of 45Ca below zero for several minutes. This suggests that there is a significant amount of Ca bound extracellularly on the umbilical side of the placental barrier. PMID- 4022955 TI - Maternal vascular lesions in placentae of small-for-gestational-age infants. AB - Placentae from 140 term pregnancies were studied. Seventy-four were from uncomplicated pregnancies in which the neonates were within the normal weight range for their gestational age. The remaining 66 placentae were from pregnancies whose infants were small for gestational age (SGA). In eight cases of this latter group a curettage of placental bed was performed during caesarean section. Maternal arterial vessels with absence of trophoblastic migration were observed in basal decidua and basal plate, and acute atherosis in parietal decidua, basal decidua and basal plate, all of them in cases of the SGA group. Furthermore, chronic vasculitis-like lesions were observed in the parietal decidua of three cases from the SGA group and in two others of the control group. No vascular lesions were found in cases of the control group when an infant's birthweight was above the 25th percentile of the normal ponderal range. Atheromatous-like lesions have been described in placental bed arteries in pre-eclampsia, systemic lupus erythematosus and SGA infants: this type of vasculopathy has also been described in rejection of renal transplants. Moreover, lesions similar to those found in chronic vasculitis were also described in the latter pathological entity. It is suggested that these vasculopathies may represent different steps of the same lesion. On the other hand, they may also be the expression of a maternal immunological attack on placental tissues causing a deficit of placentation, low birthweight being the consequence of this deficit. PMID- 4022956 TI - Conference on nucleosides and lymphocytes. PMID- 4022957 TI - Incorporation of 3H-labeled nucleosides and 3H-labeled deoxynucleosides into detergent soluble DNA. AB - Detergent soluble DNA from splenocytes of immunologically stimulated mice has been shown to incorporate [3H]dThd more rapidly than detergent insoluble DNA. In this report we compare the incorporation of other 3H-labeled nucleosides and 3H labeled deoxynucleosides and the distribution of 3H in the different size classes of detergent soluble DNA. The order of incorporation into DS DNA is [3H]dThd greater than [3H]dCyd greater than [3H]Ado greater than [3H]dGuo approximately equal to [3H]Cyd greater than [3H]dAdo greater than [3H]Guo. We also show that the previously reported slight enrichment in Gua + Cyt content is not due to preferential incorporation of dGuo or of dCyd into any one size class. PMID- 4022958 TI - The differential response of cortical and trabecular bone to aluminum administration in the rat. AB - Osteomalacia has been noted following in vivo aluminum (Al) loading in the rat by some investigators but not by others. To determine whether the response of bone to Al differs as a function of the skeletal site examined, quantitative histology of cortical and trabecular bone was done in the tibiae from control (C, n = 10), Al-treated (AL, n = 9), nephrectomized control (NX-C, n = 7), and nephrectomized Al-treated (NX-AL, n = 8) rats given 2 mg/day of Al for 4 weeks. Bone Al content was determined by histochemical methods. In cortical bone, osteoid seam width, osteoid volume, and percent osteoid area were similar for all groups. In contrast, for trabecular bone, both forming surface (means +/- SD) (5.2 +/- 3.4 vs 1.8 +/- 1.1%, P less than 0.05) and osteoid volume (1.7 +/- 0.7 vs 1.0 +/- 0.4%, P less than 0.05) increased from control values in AL, although osteoid seam width did not differ. In NX-AL, trabecular forming surface (20.2 +/- 6.7 vs 6.2 +/- 2.4%, P less than 0.01), osteoid area (13.2 +/- 5.7 vs 3.5 +/- 0.8%, P less than 0.01), and osteoid width (18.7 +/- 5.7 vs 9.7 +/- 2.3 micron, P less than 0.01) all were greater than in NX-C. Deposits of Al were undetectable in C and NX-C, were minimal in cortical bone in AL and NX-AL, but were present at 40.5 +/- 11.5 and 71.1 +/ 6.5% of trabecular surfaces in AL and NX-AL, respectively. Osteoid area and osteoid surface each correlated with trabecular bone Al. Thus, (a) osteoid accumulates in trabecular, but not in cortical, bone after 4 weeks of Al loading; (b) the extent of osteoid accumulation correlates with the bone Al content; and (c) the histologic response to Al in cortical and trabecular bone is related to local differences in the uptake of Al into bone. PMID- 4022959 TI - Retention of ingested latex particles in Peyer's patches of germfree and conventional mice. AB - Conventional and germfree mice ingested a suspension of 2-micron latex particles in drinking water for a 15-day period. Number and distribution of intestinal Peyer's patches did not differ significantly in the two types of mice. Cleared Peyer's patches were compared with regard to size and particle content. The location of particles within Peyer's patch follicles of germfree mice was similar to that of conventional mice, but the latter had significantly larger follicles and greater accumulations of latex particles. Latex concentration varied with patch location. Proximal patches contained the majority of particles in germfree mice, whereas particles were most abundant in distal patches of conventional mice. The results show that particle uptake into Peyer's patches takes place even in the complete absence of bacteria in the gut. PMID- 4022960 TI - Prolactin responses to chronic exercise in males. AB - Chronic, as well as acute, exercise increases circulating PRL in females. The response of males to repeated exercise, however, is unknown. The purpose of the present study was to examine the effects of acute and chronic exercise on plasma PRL levels in untrained males. Eight male subjects performed cycle ergometer exercise at 50% of their maximal oxygen uptake on 10 consecutive days. The subjects exercised in an environmental chamber maintained at 39 degrees C and 30% relative humidity. PRL levels were measured on days 1, 5, and 10 before exercise, and after 20 and 45 minutes of exercise. Acute exercise increased PRL levels. However, plasma levels did not significantly increase during exercise on days 5 and 10. This suggests a similarity in the PRL response to acute exercise in males and females, but a sex difference in the response to chronic exercise. PMID- 4022962 TI - Germfree research. Microflora control and its application to the biomedical sciences. Proceedings of the VIIIth International Symposium on Germfree Research. Notre Dame, Indiana, June 17-22, 1984. PMID- 4022961 TI - The use of athymic nude mice for the study of human keloids. AB - Keloid tissue has been implanted in the athymic nude mouse in order to develop an experimental animal model for the study of human keloids and hypertrophic scars. Untreated keloid tissues maintained essentially the same morphological patterns and glycosaminoglycan distributions for at least 60 days after implantation in the athymic mice. Normal human skin implanted in the same way was maintained without change in glycosaminoglycan distribution or morphologic characteristics. We suggest that this model may be useful for basic research of keloids and hypertrophic scars in that it will allow studies of morphologic, biochemical and therapeutic interrelationships under controlled conditions. PMID- 4022963 TI - Formation of hyodeoxycholate from beta-muricholate in gnotobiotic rats associated with Clostridium HDCA-1. PMID- 4022964 TI - Lack of 7 alpha-dehydroxylation in gnotobiotic gerbils associated with an octaflora including Clostridium sordellii. PMID- 4022965 TI - Urinary 3-methylhistidine excretion in germfree and conventional rats maintained on 70% of ad lib diet intake. PMID- 4022966 TI - Studies on the effect of the gut microflora on dietary nitrogen digestibility in pigs. PMID- 4022967 TI - Production of amines in monoxenic chicken inoculated with a Lactobacillus strain isolated from holoxenic (conventional) cock crop. PMID- 4022968 TI - Nitrate reduction in germfree rats. PMID- 4022969 TI - Thermal injury mortality in germfree and conventional animals. AB - Studies in germfree (GF) rats and mice demonstrated that GF animals were as sensitive if not more so to thermal injury than conventional (CV) animals. Death occurred in both groups after a similar period of time. There was no evidence of infection in either group. Using GF animals in other forms of injury such as hemorrhagic shock, others report that death occurred with equal frequency in both GF and CV animals. It is therefore postulated that sepsis cannot be the basic cause of death in severely traumatized patients. It is of utmost importance to control the toxic effect of tissue breakdown products before the vicious cycle of depressed immunological function and malnutrition ensues. A method of neutralizing the toxic effects of thermal injury by competition is described. Competitin is an "antitoxin" produced in vitro from "toxin(s)" isolated from burned human skin. Competitins to other toxin(s) have been produced and it is postulated that competitins may also be produced from the breakdown products of all forms of injury. PMID- 4022970 TI - Cleavage of lactose-lysine, a novel indicator of colonization resistance of the digestive tract. PMID- 4022971 TI - Rationale for use of beta-aspartylglycine as indicator of colonization resistance. PMID- 4022972 TI - beta-Aspartylglycine during antibiotic induced dysbacteriosis of intestinal microflora in the rat. PMID- 4022973 TI - Establishment of gnotobiotic state in guinea pigs and their response to Shigella infection. PMID- 4022974 TI - Colonization and pathogenesis of Campylobacter spp. in athymic and euthymic germfree mice. PMID- 4022975 TI - Experimental models of Clostridium difficile enterocolitis in gnotobiotic mice. PMID- 4022976 TI - Kinetics of cytotoxin production in feces of gnotobiotic mice and rats associated with two strains of Clostridium difficile. PMID- 4022977 TI - Virulence factors of Streptococcus mutans. PMID- 4022978 TI - Characterization of fusiform bacteria and clostridia isolated from feces of limited flora mice and their association to germfree mice. PMID- 4022979 TI - The instability of intestinal clostridial colonisation in living beings. PMID- 4022980 TI - Alterations in cell number, size and collagen content in livers of conventional and germfree mice bearing Schistosoma mansoni. PMID- 4022981 TI - The influence of antibiotics upon microflora-associated characteristics in man and mammals. PMID- 4022982 TI - A new workbench isolator. PMID- 4022983 TI - Forecast of antibiotic susceptibility of translocating strains of enterobacteria and pseudomonas in leukemic neutropenic patients. PMID- 4022984 TI - In vivo influence of three B-lactam antibiotics on the intestinal microflora of man. A preliminary study in gnotobiotic mice. PMID- 4022985 TI - Profile of spontaneous tumor development in germfree Lobund Wistar rats. PMID- 4022986 TI - Germfree animal as a tool to study role of gut microflora and nutrition in cancer. PMID- 4022987 TI - Spontaneous polyposis in the small intestine of germfree and conventionalized BALB/C mice. PMID- 4022988 TI - The evolution of gnotobiotic technology. PMID- 4022989 TI - Suppressive influence of methemoglobinemia due to nitrite on hepatotoxicosis due to dimethylnitrosamine (DMN) in germ-free rats. PMID- 4022991 TI - Recent advances in isolator technology: the auto-bubble. PMID- 4022990 TI - Composition of, and cholate transformation by, the predominant fecal flora of patients with colon or rectal cancer and matched controls. PMID- 4022992 TI - Recent studies of diseases demonstrating similar patterns including infectious mononucleosis (IM) and Kaposi's sarcoma (KS). PMID- 4022993 TI - Immunoresponses and natural killer activity of nude and normal mice under conventional and germfree conditions. PMID- 4022994 TI - Natural killer cell activity in germfree and conventional rats. PMID- 4022995 TI - Influence of antigen-free diet, microbial flora and host strain on natural killer cytotoxic activity in mice. PMID- 4022996 TI - The effect of the antigenic stimuli derived from the diet and microbial flora on immunoglobulin levels. PMID- 4022997 TI - Isotype distribution and specificity repertoire of 'spontaneously' occurring ('background') immunoglobulin-secreting cells in germfree mice fed chemically defined ultrafiltered 'antigen-free' diet. PMID- 4022998 TI - Comparison of bronchoalveolar lavage cells from germfree and conventional lambs. PMID- 4022999 TI - Fc receptor-dependent activation of effector function of gnotobiotic porcine pulmonary alveolar macrophages. PMID- 4023000 TI - Isolation and function of mucosal lymphocytes in the mouse. PMID- 4023001 TI - The use of flexible film isolators in the production of genetically and microbiologically defined rats and mice. PMID- 4023002 TI - Response of gnotobiotic pigs to immunization and challenge with Hemophilus pleuropneumoniae. PMID- 4023003 TI - Intestinal microecology and immune response of germfree and conventional mice in mixed trichinellosis. PMID- 4023004 TI - Combined use of isolators with laminar air flow cabinet for xenografts in nude mice. PMID- 4023005 TI - Histological and immunological evaluation of gnotobiotic C3H/He mice following i.v. administration of 8-aminoguanosine and 2'deoxyguanosine. PMID- 4023006 TI - Growth of dog intestinal mucosa xenografts in nude mice. PMID- 4023007 TI - David's story: the gift of 12 years, 5 months, and 1 day. PMID- 4023008 TI - Weighing problems in germfree environment. PMID- 4023009 TI - Sterilization issues and update for gnotobiology research. PMID- 4023010 TI - Ambient pressure ethylene-oxide sterilization of flexible film germ free isolators. PMID- 4023011 TI - Increased life span among germfree rats. PMID- 4023012 TI - Establishment of a colony of germfree spontaneously hypertensive rats. PMID- 4023013 TI - On gut membrane transport of tryptophan in the germfree mouse. PMID- 4023014 TI - Superior reproduction by BALB/C vs C3H/HeCr germfree mice fed chemically defined, ultrafiltered, antigen-free diet. PMID- 4023015 TI - Hepatotoxicity of chemically-defined diets containing polysorbate-80 in germfree and conventional mice. PMID- 4023016 TI - Bile pigments in germfree and conventional rats. PMID- 4023017 TI - [Reduction of the solubility of enamel following treatment with nicomethanol hydrofluoride]. PMID- 4023018 TI - The effect of the particle size of synthetic red iron oxide on the appearance of tablet film coatings. PMID- 4023019 TI - The preparation and characterization of poly(D,L-lactic acid) for use as a biodegradable drug carrier. PMID- 4023020 TI - Asymmetrical effect of unilateral cortical lesions and amphetamine on DRL-20: a time-loss analysis. AB - Male Sprague Dawley rats received unilateral 1.5 mm diameter focal suction lesions of either the left or right orbito-frontal cortex and were tested for response to 6 doses of amphetamine sulfate ranging from 0.5 to 1.5 mg/kg on a DRL 20 schedule of reinforcement. Right hemispheric lesion animals obtained a greater number of control reinforcements and were more sensitive to amphetamine's disruptive effects, showing a greater dose-related decrease in water rewards obtained than left lesion animals. An analysis method is introduced which combines the interactive effects of premature responses and their IRT value in a way that relates directly to reinforcement attainment. Calculated total session time made unavailable for reinforcement due to premature responding, correlated negatively (r = -.942) with the number of reinforcements obtained. PMID- 4023021 TI - Norepinephrine-facilitated eating: reduction in saccharin preference and conditioned flavor preferences with increase in quinine aversion. AB - Paraventricular (PVN) hypothalamic norepinephrine (NE) injections which facilitated feeding were nonetheless found to reduce both the unconditioned preference for saccharin and starch-conditioned preferences for almond odor and lemon taste, as well as enhancing aversion to quinine. These results add to the evidence that PVN NE elicits eating by attenuating a satiety signal. PMID- 4023022 TI - High proline levels in the brains of mice as related to specific learning deficits. AB - Hyperprolinemic PRO/Re mice have been studied as potential models for hyperprolinemia in man. In addition to high proline levels, some heretofore unreported amino acid abnormalities in the brains of PRO/Re mice are described. The T-maze and shuttlebox learning abilities of PRO/Re mice were compared with those of CD-1 mice having normal proline levels. PRO/Re mice had a significant deficit for T-maze learning, but a significantly greater aptitude for shuttlebox learning when compared to CD-1 mice. By studying the F3 progency of the PRO/Re X CD-1 cross, these strain-specific differences in learning ability for different tasks were shown to be unrelated to the differences in brain proline levels. F3 mice could be subdivided into two distinct groups: those with high proline (HP+) and low proline (HP-) titers. Other amino acids in brain tissues were essentially identical in both groups. A comparison of learning abilities of these HP+ mice with their HP- littermates showed no meaningful differences. However, the slightly slower rate at which HP+ mice acquired shuttlebox learning was sufficiently consistent over the 8 day training period so that it became significant. These results do not support the hypothesis that high levels of proline in brain tissues and blood are necessarily accompanied by impaired learning and memory, but are in agreement with those studies of hyperprolinemia in man that suggest no consistent learning deficits in hyperprolinemic subjects. The results seem to validate the suitability of the PRO/Re mouse as a model for hyperprolinemia in man. The data suggest also that the altered amino acid pattern in brains of PRO/Re mice has multiple etiologies.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4023023 TI - Effects of opioids and phencyclidine in combination with naltrexone on the acquisition and performance of response sequences in monkeys. AB - In each of three components of a multiple schedule, monkeys were required to emit a different sequence of four responses in a predetermined order on four levers. Sequence completions produced food under a fixed-ratio schedule. Errors produced a brief timeout. One component of the multiple schedule was a repeated acquisition task where the four-response sequence changed each session (learning). The second component of the multiple schedule was also a repeated acquisition task, but acquisition was supported through the use of a stimulus fading procedure (faded learning). In a third component of the multiple schedule, the sequence of responses remained the same from session to session (performance). Heroin, methadone, cyclazocine and phencyclidine each produced dose-related decreases in overall response rate. At high doses which produced equivalent rate-decreasing effects, cyclazocine and phencyclidine generally produced greater disruption of accuracy in the learning component than did heroin or methadone. Naltrexone 5.6 microgram/kg shifted to the right by approximately 1/2-log unit the heroin and methadone dose-effect curves, but produced little or no change in the cyclazocine dose-effect curves. At 56 micrograms/kg naltrexone completely antagonized both the rate-decreasing and error-increasing effects of heroin and methadone. The same dose of naltrexone tended to produce greater antagonism of the effects of cyclazocine on accuracy than on rate, which was shifted by only 1/4-log unit. In contrast, naltrexone failed to antagonize the effects of phencyclidine on either rate or accuracy. Thus it would appear that while cyclazocine and phencyclidine produce similar disruptions in the accuracy of a discrimination, the effects of each are differentially sensitive to antagonism by naltrexone. PMID- 4023024 TI - Self-administration of phentermine by naive rats: effects of body weight and a food delivery schedule. AB - Food deprivation has been shown to increase intravenous self-administration of amphetamine and cocaine. In the present experiment, the response rates of four groups of eight rats for intravenous infusions of phentermine under free-feeding (FF) and 80% free-feeding weight (FFW) conditions in the presence and absence of a fixed time 1 min (FT-1) food delivery schedule, were compared with those of saline reinforced animals under identical conditions. The findings showed that: (1) Overall, response rates of phentermine-reinforced animals were significantly greater than were those of saline-reinforced animals; (2) 80% FFW animals self injected significantly greater amounts of phentermine than did FF animals; and (3) the operation of an FT-1 schedule failed to affect the rate of phentermine reinforced responding. PMID- 4023025 TI - Cathinone, cocaine and methamphetamine: similarity of behavioral effects. AB - The discriminative stimulus properties of (+/-)-cathinone were tested by training eight rats to discriminate between the interoceptive cues produced by 0.6 mg/kg (+/-)-cathinone and saline in a food-reinforced, two lever operant task. Doses of cocaine and methamphetamine were observed to transfer to the cathinone cue and all three drugs exhibited decreased discriminative performance with decreasing doses. The ED50 for (+/-)-cathinone, (+/-)-methamphetamine and cocaine were 0.23, 0.17, and 1.97 mg/kg, respectively, and the three curves were shown to be parallel. These data indicate the possibility of a common mechanism/site of action for these three stimulants, presumably by their actions upon central dopaminergic neurons. PMID- 4023026 TI - Behavioral responses of high and low active male rats to the chronic ingestion of desipramine. AB - Male rats arbitrarily selected for high and low motor activity (HA and LA-rats) were submitted to the chronic ingestion (30 days) of desipramine (DSP) in doses of about 1.5, 3 and 6 mg/kg/24 hr. Their motor activity was assessed in an animal activity monitor providing a measure of total horizontal movements and vertical movements and in a hole-board providing a measure of locomotion, head-dipping and grooming. There were significant differences between HA and LA-rats in their behavioral response to DSP treatment. At the doses used DSP did not affect horizontal and vertical movements and hole-board locomotion or exploration in HA rats (Experiment 1). In LA-rats, however (Experiment 2), these motor activities were significantly stimulated by DSP. Such effect was dose dependent; 1.5 mg/kg/24 hr was ineffective while 6 mg/kg/24 hr produced a clear cut reversion of hypoactivity. It is speculated that DSP treatment increased resistance of LA-rats to the mild stress caused by testing. PMID- 4023027 TI - Opiate self-administration in adult offspring of methadone-treated female rats. AB - Chronic treatment of female Sprague-Dawley rats with methadone 5 mg/kg IP throughout gestation and lactation resulted in an increased oral self administration (S.A.) of morphine by their 85-90-day-old offspring. By day 16 of the S.A. treatment schedule methadone offspring were taking 75 to 80% of their total fluid intake as morphine solution when given a choice between morphine solution and water, while control offspring under the same conditions took 33% of their total fluids as morphine solution. When the subjects were again given a choice between water and morphine solution following a 12-day drug free period, methadone offspring drank a significantly greater percentage of morphine solution than controls. Methadone S.A. in methadone offspring was not different from controls. The reasons for this marked difference between morphine and methadone S.A. are not clear. However, it does appear that chronic maternal exposure to methadone may facilitate development of a morphine-S.A. behavior in their offspring. PMID- 4023028 TI - Acute soman effects in the juvenile baboon: effects on a match-to-sample discrimination task and on total blood acetylcholinesterase. AB - Male juvenile baboons, trained on a match-to-sample operant discrimination task, were given acute intramuscular injections of soman (methyl pinacolyl phosphonofluoridate) at 1.0, 2.0, 3.0, 4.0, and 5.0 micrograms/kg. The different doses were given in a mixed order just before a behavioral test session. Just prior to administration of each soman dose and immediately following the 2-hr behavioral test session, a sample of blood (0.5 ml) was drawn from the baboon and analyzed for inhibition of acetylcholinesterase activity. Thereafter, blood sampling was accomplished at weekly intervals and soman was administered again only when whole blood acetylcholinesterase reached at least 80% of pre-soman control level. Behavioral effects of soman included a slowing of response times, a decrease in extra inconsequential responses, a decrease in responsiveness to the visual stimuli and an increase in errors. These effects were observed when acetylcholinesterase (AChE) levels fell to 25 mumoles/hr/ml blood or less. The threshold dose for behavioral effects was very close to the dose of soman which induced seizures. PMID- 4023029 TI - Dissociation of tolerance to the hypothermic and tachycardic effects of ethanol. AB - Tolerance to the cardioacceleratory and hypothermic effects of ethanol was studied in unanesthetized, freely-moving rats surgically implanted with EKG electrodes and biotelemetric temperature sensors. Different groups received 0.0, 1,0 or 2.0 g ethanol/kg body weight in injections given every other day for a total of nine injections. Heart rate and body temperature were recorded for 1 hr before and 2 hr after each injection. Ethanol initially induced a monophasic dose related cardioacceleration (80 bpm) and hypothermia (1.0 degrees C) that persisted throughout the 2-hr sample period. Tolerance developed to the hypothermic, but not to the tachycardic effect of ethanol. Assuming that tolerance depends on level of impairment in specific neuronal pathways, this outcome suggests that these two effects of ethanol are not mediated through a common autonomic mechanism (e.g., vasomotor depression) and/or that tolerance to the hypothermic effect is due to alterations in pathways unique to the thermoregulatory system. Overall, the finding is consistent with those of studies showing development of tolerance to depressant, but not to excitatory drug effects. PMID- 4023030 TI - The influences of ethanol and other factors on the excretion of urinary salsolinol in social drinkers. AB - Salsolinol, a substance that may participate in the development of alcoholism, has been identified in urine and other biological samples from alcoholics. Differentials have been observed between alcoholics and controls. Salsolinol forms when dopamine reacts with acetaldehyde, which may exist in higher concentrations in the blood of alcoholics after alcohol ingestion. Hence, it was postulated that there is a relationship between level of social drinking and the elaboration of salsolinol. Salsolinol is also found in certain food and beverage products. Eighty volunteers, balanced for gender, social drinking level, ethanol dose administered and experimental diet provided urine samples 90 minutes and three hours after ethanol was consumed. Salsolinol levels were analysed in urine using high performance liquid chromatography. A 24 hour carryover effect was observed. Diet, ethanol dose and social drinking level had main and interactive effects on excreted quantities of salsolinol. Gender, situational stress and cigarette smoking had minor if any influence on salsolinol excretion. While there was no evident difference in amounts of salsolinol excreted by light and heavy drinkers in the absence of external sources of salsolinol, heavy social drinkers excreted less salsolinol than did light drinkers after consuming a "salsolinol enriched" diet, suggesting that they differ in some aspect of absorption, distribution, or metabolism of salsolinol after drinking ethanol. Accordingly, studies that attempt to determine whether salsolinol has any relationship to drinking behaviour in humans should be particularly concerned with salsolinol that occurs in exogenous sources. PMID- 4023031 TI - Skin penetration of minerals in psoriatics and guinea-pigs bathing in hypertonic salt solutions. AB - Penetration of electrolytes through the human skin was measured in healthy volunteers and in psoriatic patients after bathing in the Dead-Sea or in simulated bath-salt solutions. Significant increases in the levels of serum Br, Rb, Ca and Zn were noticed only in the psoriatic patients after daily bathing in the Dead-Sea for a 4-week regimen. Guinea-pigs "bathed" in simulated Dead-Sea bath-salt solutions containing radionuclides of Ca, Mg, K and Br. Traces of each radionuclide were detected in the blood and in some internal organs after 60 minutes of bathing. The radionuclides showed a physiological pattern in their organ distribution. Even though the whole investigation was carried out in hypertonic solutions, there is a definite penetration of salts through healthy (human and guinea-pigs) and damaged (psoriatic) epidermis. This finding suggests that improvement of the psoriatic condition after bathing in the Dead-Sea, may be partly attributed (in addition to ultraviolet irradiation) to the minerals' effect on the psoriatic skin. PMID- 4023032 TI - Novel bis(5-arylamino-2-oxo-4-thiazolidinylidene)hydrazine derivatives as potential antineoplastic agents. AB - A new series of N,N'-bis(5-arylamino-3-benzyl-2-oxo-4 thiazolidinylidene)hydrazine s has been prepared for potential anticancer activity. The synthesis was achieved by reacting 3-benzylthiazolidin-2-one-4 thione with its 4-hydrazone derivative to give N,N'-bis(3-benzyl-2-oxo-4 thiazolidinylidene)hydrazine, which was subjected to dibromination followed by reaction with various primary aromatic amines. Some compounds were evaluated against leukemia P 388 in the mouse. No significant antitumor activity was observed. PMID- 4023033 TI - Photochemical decomposition of phenazone derivatives. Part 7: Mechanism of decomposition in aqueous solutions. AB - Kinetic studies, supplemented by the isolation and identification of the products of decomposition, have proved the process of photochemical decomposition of phenazone derivatives to be a complex reaction, involving several successive parallel reactions, one of which is predominant depending on the concentration of the solution and the atmosphere above it. In an oxygen-free atmosphere and at low concentrations (10(-4) mol/dm3) decomposition is almost wholly the result of second photolysis of zero order to aziridine derivative----aniline----isonitrile. At higher concentrations (10(-3)-10(-2) mol/dm3), the contribution from the reaction of water photoaddition to the double bond C3-C4 increases. Whereas at concentrations of order greater than or equal to 10(-2) mol/dm3, photoisomerization to imidazole derivatives is predominant. In air, one onserves additionally a second reaction of photooxidation to 4-hydroxy-phenazone----1 acetylo-1-methyl-2-phenyl-hydrazine, a reaction of photodemethylation at N2 with simultaneous oxidation to the 4-ketoderivative, and reactions of hydrolysis characteristic for the individual derivatives. The principal primary photolytic reaction for the group of compounds studied consists in cleavage of the N1-N2 bond of the pyrazoline ring. PMID- 4023034 TI - Temperature effects on the binding efficiency of starch pastes. AB - The effect of temperature on the binding efficiency of yam starch and cassava starch pastes has been investigated. Starch pastes prepared at different temperatures were used to granulate lactose powder and the resulting granules and tablet properties were evaluated. Increased average granule size and decreased percentage fines were observed as the pasting temperature was increased upto a certain level and then there was a decrease in average size and increase in amount of fines as the pasting temperature was further increased. Granules prepared with yam starch pastes exhibited relatively lower amount of fines and larger average granule size. The corresponding tablets also showed higher crushing strength values and were less friable. Although the disintegration time of tablets was found to increase with the temperature of pasting of both the starches, no relationship between the pasting temperature and the crushing strength of tablets was observed. The release of amylose/amylopectin from starch grains, the amylopectin chain length and the amount of free molecular components as the pasting temperature increased are believed to be the factors contributing to the increased binding efficiency of the starch pastes. PMID- 4023035 TI - Studies on the release of solubilized drugs from ointment bases. Part 10: Modelling of the drug release process of chloramphenicol from emulsive ointments (W/O)--discussion. AB - A mathematical model has been analyzed for the liberation process of substances (chloramphenicol) from emulsive ointments (W/O). Limitarying approximations have been derived which are useful for practical calculations. These approximations have been elaborated for the following cases: since the mass transfer resistance of diffusing substance occurs in the continuous phase, since the mass transfer resistance occurs only in the dispersed phase, then the mass transfer resistance in both phases is comparable. Experimental investigations have been carried out for the liberation process of substances from emulsive ointments. A good qualitative agreement has been found between the theoretical projections and experimental results. PMID- 4023036 TI - Spectrofluorometric analysis in biological fluids of the dihydrochloride of (-) cis-2,8-dimethyl-2,3,4,4a,5,9b-hexahydro-1-H-pyrido[4,3b]indole (DH 1011), a prospective antiarrhythmic. PMID- 4023037 TI - Determination of vitamin A and E in pharmaceutical preparations by HPLC method. PMID- 4023038 TI - [The effect of water structure on cyclodextrin inclusion and light sensitivity of epinephrine]. PMID- 4023039 TI - [Oxidation of phenothiazine and its N-methyl derivative by the combination of iodobenzene and vanadium acetylacetonate]. PMID- 4023040 TI - [Sterilization--thermal procedures. 3. Hot air sterilization, flame application, chemothermic methods, combined methods]. PMID- 4023041 TI - Effect of reduced calcium on lysophosphatidylcholine-induced cardiac arrhythmias. AB - Lysophosphatidylcholine (LPC) had recently been shown to accumulate in the ischemic heart and was demonstrated to be arrhythmogenic in perfused hearts. The present study was designed to examine the effects of calcium and verapamil on LPC induced arrhythmias. Rat hearts were perfused through the aorta with oxygenated Krebs-Henseleit buffer at 37 degrees C. The occurrence of ventricular fibrillation was dependent on the LPC concentration and perfusion time. In subsequent experiments, each heart was perfused with a buffer containing 20 microM LPC for 3 min and was followed with a 10 min washout period. Ventricular fibrillation occurred in all 8 control experiments. When the Ca2+ concentration was reduced to half, only 3 out of 8 hearts fibrillated. In the presence of 0.2 mg/1 of verapamil, 7 out of 9 hearts fibrillated, and the time to fibrillation was not increased significantly by verapamil. These results suggest that calcium may be important in LPC-induced arrhythmias, and this effect is not significantly attenuated by the Ca2+ antagonist, verapamil. PMID- 4023042 TI - Effect of diltiazem on in vitro rabbit bladder function. AB - The relationship between extracellular calcium and urinary bladder function was investigated by studying the effect of the specific calcium antagonist diltiazem on the functional ability of the in vitro whole rabbit urinary bladder to empty in response to pharmacological stimulation. The bladder was found to require an extracellular calcium concentration of 4.5 X 10(-4) M to elicit near complete cholinergic-mediated emptying. Diltiazem (1 X 10(-6) - 1 X 10(-4) M) inhibition of bladder function was competitively antagonized by increasing the extracellular calcium concentration (0.45 X 10(-4) - 3.6 X 10(-4) M). In the absence of diltiazem, alterations in the extracellular calcium concentration between 0.45 X 10(-4) and 3.6 X 10(-4) M had no significant effects on bladder response to bethanechol. KCl-mediated bladder emptying was significantly more sensitive to diltiazem inhibition than was bethanechol-stimulated emptying. Even at the intermediate diltiazem concentration of 1 X 10(-5) M, increasing the extracellular calcium concentration did not completely reverse the inhibitory effect of diltiazem on bladder response to KC1. These findings are consistent with the hypothesis that diltiazem at low concentrations may inhibit extracellular calcium influx while at higher concentrations translocation of intracellular stores of calcium may be inhibited as well. The study also suggests that diltiazem is capable of inhibiting urinary bladder function and deserves further consideration as a possible therapeutic agent in certain forms of urinary bladder dysfunction. PMID- 4023043 TI - Pulmonary cytochromes P-450 from rabbits treated with phenobarbital. AB - Pretreatment of rabbits with phenobarbital caused significant increases in total pulmonary cytochrome P-450 content, benzo(a)pyrene hydroxylase and 7 ethoxycoumarin O-deethylase activities and to a lesser extent in benzphetamine N demethylase activity in lung microsomes. However, 7-ethoxyresorufin O-deethylase activity was not significantly altered. In addition, the pulmonary concentration of the cytochrome P-450-metyrapone complex was increased significantly. Column chromatography of the pulmonary monooxygenases demonstrated that in untreated and phenobarbital-treated rabbits, cytochromes P-450I and P-450II constituted the major forms of cytochrome P-450 isozymes. In addition, the chromatographic studies showed that pretreatment with phenobarbital caused an increase in the content of cytochrome P-450I, but not of cytochrome P-450II. These observations were confirmed by subjecting the pulmonary cytochromes to gel electrophoresis, and staining of the gels for protein and heme. PMID- 4023044 TI - Effects of morphine and naloxone on restraint-stress ulcers in rats. AB - Rats were starved for 24 h. Morphine sulphate (1.0, 2.0 or 4.0 mg/kg i.p.) or naloxone-HCl (12.5, 25 or 50 mg/kg i.p.) was administered prior to 3 h of cold restraint stress. Morphine at 4.0 mg/kg significantly reduced the ulcer severity relative to saline-injected controls and to naloxone-treated rats. Naloxone increased the ulcer incidence and ulcer severity when compared to controls and morphine-treated rats. These results suggest that endogenous opioids released during stress may attenuate the pathological effects of stress. PMID- 4023045 TI - Cholecystokinin-induced hypothermia: possible involvement of serotoninergic mechanisms in the rat hypothalamus. AB - The thermal effects of rats which were pretreated with 5,7-dihydroxytryptamine to deplete hypothalamic 5-hydroxytryptamine (5-HT) or with a 5-HT receptor blocker to intrahypothalamic administration of cholecystokinin (CCK) were compared with those of control rats. The CCK-induced hypothermic response was attenuated by pretreatment of the rats with either hypothalamic 5-HT depletion or receptor blockade. The reduction in the CCK hypothermia in the treated rats was due to the reduction of metabolic and vasomotor response. The data indicate that CCK may act on a 5-HT pathway within the hypothalamus to induce its hypothermia by promoting a reduction in metabolic heat production and an enhancement in heat loss in rats. PMID- 4023046 TI - Phentolamine and rat aortic smooth muscle responsiveness to potassium chloride, isoproterenol and norepinephrine. AB - Rat aortic smooth muscle responsiveness to potassium chloride and isoproterenol in the presence of the alpha-adrenergic blocker phentolamine was investigated. A A significant decrease in the response of the vascular smooth muscle of aorta to low concentrations of potassium chloride (KCl; 8-12 mM) in the presence of phentolamine was observed. However, no effect of phentolamine was seen at KCl concentrations greater than 16 mM. Isoproterenol-induced relaxation was significantly increased in aortic smooth muscle incubated with phentolamine. Phentolamine also attenuated the contraction induced by high concentrations of isoproterenol. No long-lasting effect of the alpha-adrenergic blocker was apparent since the response to norepinephrine was not altered following a 1-hour washout of phentolamine after the isoproterenol dose-response curve. The results of this study suggest that: (i) phentolamine has no long-lasting effects on rat aortic smooth muscle; (ii) since the rat thoracic aorta has a sparse adrenergic innervation, the decrease in responsiveness to KCl in the presence of phentolamine is most likely due to a nonspecific effect on the vascular smooth muscle as opposed to blocking the effects of norepinephrine released from adrenergic nerve terminals, and (iii) the increased relaxation response to isoproterenol may be due to a blockade of the alpha-receptors activated by isoproterenol. PMID- 4023047 TI - Altered vascular reactivity in the rabbit during hypercholesterolemia. AB - Rabbits were fed a 0.6% cholesterol diet (HC) for 4, 6 or 8 weeks. Age- and sex matched controls (C) were fed rabbit chow. Isometric contractions with cumulative doses of norepinephrine (NE), histamine (HIS) and serotonin (5-HT) were measured in isolated aortic rings. Serum cholesterol levels in female HC animals increased approximately 19, 20 and 25 times control values, and male HC animals increased approximately 17, 20 and 18 times control values after 4, 6 and 8 weeks, respectively. In the present study, altered vascular responsiveness during hypercholesterolemia was demonstrated in isolated vessels with major changes occurring after 4 weeks. Female HC rabbits exhibited increased maximal responses to all agents tested and were greater than male HC rabbits. Male HC rabbits had increased maximal responses to NE and HIS but not 5-HT. Significant changes were also observed in both male and female HC animals at 6 and 8 weeks, however these were somewhat attenuated when compared to 4-week HC animals. These results suggest that changes in vascular responsiveness due to hypercholesterolemia can be demonstrated very early after the onset of hypercholesterolemia and can be demonstrated in isolated vessels bathed in cholesterol-free media. PMID- 4023048 TI - Effect of dilazep on coronary and systemic circulations. AB - In order to assess the effects of dilazep on central hemodynamics and regional flows, 0.2 mg/kg of the drug were administered intravenously to 6 open-chest anesthetized dogs. Hemodynamic and flow measurements were performed under control conditions, and approximately 5, 10 and 25 min after treatment. Dilazep caused a marked and sustained reduction of coronary resistance and increased coronary blood flow. Flow increased uniformly in the subendocardial and subepicardial layers of the left ventricle so that no significant change occurred in the endo/epi flow ratio. Dilazep caused a significant reduction of total systemic resistance and aortic pressure, however flow to the liver, kidney and spleen was not reduced. We conclude that dilazep exerts a dilating action on the coronary and systemic arterial beds and increases uniformly regional myocardial blood flow. Dilazep does not alter the transmural distribution of coronary blood flow and does not impair kidney, liver and spleen perfusion. PMID- 4023049 TI - A common single binding site for many psychotropic drugs on human alpha 1-acid glycoprotein. Therapeutically relevant observation? PMID- 4023050 TI - Single oral dose pharmacokinetics of amitriptylinoxide and amitriptyline in humans. AB - Eleven healthy volunteers were examined in a pharmacokinetic study. After oral administration of 50 mg amitriptylinoxide or 50 mg amitriptyline the plasma levels of amitriptylinoxide and its main metabolites amitriptyline and nortriptyline were investigated over 24 hours. The results indicate that amitriptylinoxide is more rapidly absorbed than amitriptyline and eliminated with a mean half-life of 1.5 hours. The change with time in the levels of amitriptyline formed from the oxide is similar to that of amitriptyline after ingestion of amitriptyline. However, the plasma concentration of amitriptylinoxide, reflected by the area under the time curve (AUC), exceeds that of its metabolite amitriptyline twelvefold. PMID- 4023051 TI - The AMDP system for the documentation of psychiatric symptoms: course and effectivity of a training seminar. AB - In an AMDP training seminar on psychopathology, the possible learning effects were studied. Eighteen psychiatrists with varying levels of experience saw five video tapes of patient explorations within one and one-half days. The first and the last tape were identical. This enables a comparison of the ratings of these two tapes. The extent to which the raters agreed with regard to the frequencies of the AMDP items was examined both in relation to "present"-"absent" as well as with regard to the severity. The interrater reliability clearly increased in the course of the training. This increase was greater with the inexperienced raters than with the experienced group. The greatest change between the first and the last rating occurred between "mild" and "absent", thus indicating a threshold problem in the assessment of psychopathological symptoms. PMID- 4023052 TI - Dielectric properties of mammalian brain tissue between 1 and 18 GHz. AB - A newly developed frequency domain technique was used to measure the dielectric properties of white matter, grey matter and macerated rabbit brain at 20 and 37 degrees C. An analysis of the data showed that between 1 and 4 GHz there were substantial contributions from processes other than the gamma dispersion. However, above 7.5 GHz it appeared that mainly free water was relaxing although evidence of a small spread of relaxation times was found for the bulk water in the white matter. Mouse and rat brain were also measured but no significant differences were found between the species. The quantity of bound water was estimated but there was no evidence of a difference in the amount between either the tissues or the temperatures. PMID- 4023053 TI - Geometrical factors in the cardiac nuclear probe. AB - The design of the collimator for the assessment of left ventricular function with a non-imaging detector is considered. When certain simplifying assumptions are made concerning the distribution of the background and the ventricular activity, the statistical variation in the calculated ventricular count rate is examined for various detector-collimator combinations. For detectors with sufficient diameter to give reasonably low counting errors it is shown that the focused multihole type of collimator is preferable and the optimum parameters of this are given. It is shown that when the simplifying assumptions are relaxed there is still a preference for the use of a focused multihole collimator. PMID- 4023054 TI - Texture analysis in radionuclide tomographic liver imaging. AB - In clinical trials assessing the value of radionuclide tomographic liver imaging there has been no significant increase in diagnostic accuracy when conventional views have been viewed with tomographic images. In an effort to increase the diagnostic value of tomography, we have applied some simple methods of texture analysis to both phantom and patient tomograms in order to quantify different uptake patterns. Three algorithms were used which look at the differences between a pixel and its near neighbours. In phantom experiments, the variation of image texture with image noise was quantified. Accurate values of texture were obtained for images of the phantom containing various sizes of cold spots. Detection limits were then calculated for the different sizes of cold spots. It was found that 1.5 cm cold spots could be detected with a collection time of approximately 25 min, the usual collection time for livers being 20 min. The theoretical detection limits were checked experimentally and found to agree well with experimental values. A preliminary clinical survey was made applying texture analysis to eight images from normal livers and eight from abnormal (metastatic) livers. Although the sample was small, good separation between normals and abnormals was obtained. PMID- 4023055 TI - The influence of oxygenation on the 19F spin-lattice relaxation rates of fluosol DA. AB - The spin-lattice relaxation rates (1/T1) were measured at 94.1 MHz for six peaks in the 19F NMR spectrum of the perfluorochemical blood substitute fluosol-DA, which contains a mixed emulsion of perfluorodecalin and perfluorotripropylamine. Each of these rates increased linearly with the percentage of oxygen dissolved in the emulsion. Relative values of the linear increase for different peaks established that, for perfluorotripropylamine in the mixed emulsion, the oxygen fluorocarbon interaction is loosely but preferentially oriented in a manner similar to that previously established for other pure fluorocarbons. The uncertainty in the oxygen level estimated from T1 measurements is somewhat less than 5% O2 and it is thus established that quantitative non-invasive oxygenation measurements can be made to sufficient precision by this approach, using fluosol DA and 19F spin-lattice relaxation. PMID- 4023056 TI - Indicator dilution approach to NMR signal-flow curves. AB - An indicator dilution model for the dependence of NMR signal on flow rate is presented. The model explains the enhancement in NMR signal observed at low flow rates and the reduction in NMR signal at high flow rates. It also produces an excellent fit to original NMR flow data, which are also presented. PMID- 4023057 TI - Cardiac response to pulsed magnetic fields with regard to safety in NMR imaging. PMID- 4023058 TI - The problem of tissue equivalence in negative pion dosimetry. PMID- 4023059 TI - The selection of stopping power and mass energy absorption coefficient data for the HPA Code of Practice for dosimetry. PMID- 4023060 TI - Hyperthermia dough: a fat and bone equivalent phantom to test microwave/radiofrequency hyperthermia heating systems. PMID- 4023061 TI - An x-ray collimator design for raster scanning geometries. PMID- 4023062 TI - Effect of intermittent, supine cervical traction on the myoelectric activity of the upper trapezius muscle in subjects with neck pain. AB - This study was undertaken to compare the myoelectric activity of the upper trapezius muscle before, during, and after intermittent, supine cervical traction. Twelve people with diagnosed disease or injury of the cervical spine served as subjects. Electromyographic recordings were taken from the upper trapezius muscle with bipolar surface electrodes. The subjects were treated with 20 minutes of intermittent, cervical traction at a force of 8% of their body weight. Recordings were taken with the subjects in the supine position before the traction, during one pull and release phase of the 10th and 20th minutes of traction, and after completion of the traction treatment. An analysis of variance with repeated measures showed no significant differences in the myoelectrical activity during the six time periods measured. The results of this study do not support the clinical use of intermittent, supine traction to produce cervical muscle relaxation. PMID- 4023063 TI - Biomechanical comparison of rising from two types of chairs. AB - This study compared the joint moments and ranges of motion of healthy subjects and patients during rising from a standard chair with a seat height of 0.43 m and a specially designed chair (E-Z Up Artherapedic Chair) with a seat height of 0.64 m. Ten healthy male subjects and four male patients with lower extremity disabilities rose from each chair with and without the use of their upper extremities. Hip, knee, and ankle joint moments and angles were calculated with film analysis and force plate data. An analysis of variance with repeated measures showed the following results for the healthy subjects: 1) no effect of upper extremity use on joint angles, 2) no effect of chair type on ankle joint angles or moments, 3) significantly smaller hip and knee flexion angles with use of the E-Z chair than of the standard chair (p less than .05), and 4) significantly smaller hip and knee extension moments with use of the E-Z chair than of the standard chair (p less than .05) or with use of the upper extremities. Similar results were found with the four disabled subjects. Use of the E-Z chair can significantly decrease the joint moments and ranges of motion needed at the hip and knee and thus make rising from a chair less stressful to these joints. PMID- 4023064 TI - Effects of clinical infrared laser on superficial radial nerve conduction. AB - The purposes of this study were to demonstrate the effects of infrared laser radiation on the sensory nerve conduction of a specified peripheral nerve in man and determine temperature changes in the tissue surrounding the treated nerve. Twenty healthy adults were divided into three groups: control (n = 5); experimental (n = 10), infrared laser radiation at 20 sec/cm2; and experimental (n = 5), infrared laser radiation treatment at 120 sec/cm2. Antidromic sensory nerve conduction studies were performed on the superficial radial nerve of each subject's right forearm. The infrared laser radiation was applied at a fixed intensity for five 1-cm2 segments. Latency, amplitude, and temperature measurements were recorded pretest; posttest; and posttest intervals of 1, 3, 5, 10, and 15 minutes. An analysis of variance with repeated measures was used to examine the data. No significant change was noted in the distal sensory latency or amplitude of the evoked sensory potential in either experimental or control groups as a result of the applications of the infrared laser radiation treatment. This study demonstrates that infrared laser used at clinically applied intensities does not alter conduction of sensory nerves nor does it elevate the subcutaneous temperature. PMID- 4023065 TI - Effects of selected assistive devices on normal distance gait characteristics. AB - The purpose of this study was to investigate the effects of selected assistive devices on normal standards of gait. The gait characteristics of stride length, step length, step width, and foot angle were analyzed for 24 right-dominant, healthy men under four conditions: right ankle-foot orthosis (AFO), right hemiplegic arm sling (HAS), both devices (AFO+HAS), and no devices. The dependent variables were measured by a standard method from ink traces left by subjects walking on newsprint. Order of conditions was controlled, and cadence remained consistent across all four conditions for each subject. The AFO and AFO+HAS conditions produced statistically significant changes from normal gait characteristics. The HAS alone did not produce significant changes. Data from the study may be used as a basis for goal setting and as a guideline for the optimal level of function possible for a person wearing these devices. The extent of the patient's orthopedic and neurologic involvement should of course be considered. PMID- 4023066 TI - The relationship of heel contact in ascent and descent from jumps to the incidence of shin splints in ballet dancers. AB - I conducted a study to determine whether ballet dancers with a history of shin splints make heel contact on ascent and descent from jumps less often than dancers without this history. Sixteen dancers were filmed as they executed a sequence of jumps at two different speeds. Eight of the subjects had a history of shin-splint pain; eight had no such history. The film was viewed on a Super 8 movie projector. Heel contacts on ascent and descent from jumps were counted. Double heel strikes (heel rise between landing and pushing off) were also counted. A nonparametric t test showed no differences between the two groups in the number of contacts on ascent or descent. The dancers with a history of shin splints, however, demonstrated more double heel strikes (p = .02) than the other group. Clinically, this finding may represent a lack of control or a tight Achilles tendon or both. Further study is necessary to confirm these theories. For treatment and prevention of shin splints, a clinician must evaluate a dancer's jumping technique and then provide systematic training to develop the skin strength, flexibility, and coordination that make up control. PMID- 4023067 TI - One method for assessing the effectiveness of fast brushing. AB - The purposes of this study were to determine if fast brushing of the skin overlying a muscle is effective in increasing the sensitivity of the stretch reflex of that muscle and to detect the optimal rate and duration of brushing to elicit this effect in healthy adults. The stretch sensitivity of the right lateral gastrocnemius muscle was measured by EMG activity and force produced by the abrupt tap of the Achilles tendon before and after fast brushing. Peak-to peak EMG and force from 10 taps were established. Eight different conditions (two control and six experimental brushing) were applied to 10 healthy adult subjects (age range, 30 to 46 years). The experimental conditions included rotary brushing at 5 Hz, 180 Hz, or 360 Hz for 5 seconds or at 5 Hz, 180 Hz, or 360 Hz for 30 seconds. Postbrushing taps began 30 seconds after the brush was turned off and continued every 5 minutes for 30 minutes. This method of fast brushing did not increase the stretch sensitivity of the muscle in healthy adults. Possible factors influencing the results of the study and recommendations for future studies are presented. PMID- 4023069 TI - Unilateral traction in conjunction with heat modalities, proper positioning, and exercises for a herniated nucleus pulposus. A case report. PMID- 4023068 TI - Temporomandibular joint dysfunction syndrome. A clinical report. AB - We have presented two clinical case reports of patients with TMJ dysfunction syndrome as an example of coordinated treatments between dentists and physical therapists. The clinical profiles of these patients with craniocervical pain were compiled from comprehensive physical therapy and dental-orthopedic evaluations. The significance of the relationship between the rest position of the mandible and forward head posture has been shown by the changes observed after correction of the postural deviations and vertical resting dimensions by dental treatments and physical therapy. Additional research is necessary to determine long-term effects of this combined approach in TMJ dysfunction syndrome. PMID- 4023070 TI - Beyond lecture and laboratory in the physical therapy classroom. AB - The purpose of this paper is to describe how two teaching models, the Inquiry Training Model and the Simulation Model, have been adapted for use in the physical therapy classroom. To help students synthesize the various physical therapy skills they were learning, variations of the Inquiry Training Model and the Simulation Model were used in addition to standard lectures and laboratories to teach the Evaluation Unit to junior level physical therapy students. The feedback obtained at the end of each class from both students and faculty members indicated that the learning experiences were considered both helpful and fun. This article summarizes the important components of the Inquiry Training Model and the Simulation Model. I recommend learning experiences based on these models to augment lecture and laboratory classes. PMID- 4023071 TI - Nuclear shifting. PMID- 4023072 TI - Children's cycle times. PMID- 4023073 TI - [Franco-British colloquium on phlebology. Chichester, 26-28 April 1984]. PMID- 4023075 TI - [Sclerotherapy]. PMID- 4023074 TI - [The swollen leg. Edemas of venous origin]. PMID- 4023076 TI - [Venous ulcers]. PMID- 4023077 TI - [The swollen leg. Lymphedema]. PMID- 4023078 TI - [Static disorders or venous pathology of the foot?]. AB - Three types of disorder observed in the foot may have either a mechanical or a vascular aetiology. They are: A) Painful or tired legs, caused by: eversion, inversion or arch collapse of one or both feet. TREATMENT: corrective or compensatory soles depending on the joint mobility and the integrity of the skin. B) Metatarsalgia due to static disorders, incorrect shoes or vascular disorders. TREATMENT: orthopaedic soles, appropriate shoes. C) Burning pain in the toes exacerbated by heat, relieved by cold, due to claw or lateral deformity of the toes or compression of the forefoot and toes (shoes, stockings). TREATMENT: appropriate shoes, protective or corrective orthoplasties. PMID- 4023079 TI - [Value of vascular function tests in complicated venous pathology]. AB - The authors define their approach to vascular function tests (VFT) and the situations in which they may be useful in the diagnosis of complicated, associated or secondary venous disease. They present various pathological cases (superficial phlebitis, swollen leg, calf pain, deep venous obstruction syndrome, intermittent claudication, subacute ischaemia, trophic disorders). In general, VFT are able to: demonstrate the haemodynamic signs of venous stasis, recognise and analyse the various forms of diabetic angiopathy and quantify the degree of ischaemia in the presence of PVD associated with venous symptoms. VFT are particularly useful when the problems to be studied have been carefully defined by means of a thorough clinical examination. PMID- 4023080 TI - [Diagnostic and therapeutic problems posed by the association of arterial disease and chronic venous insufficiency of the lower limbs]. AB - The association of arterial disease and chronic venous insufficiency of the lower limbs poses a number of diagnostic and therapeutic problems. It is useful to define, at the time of diagnosis, which patients are suitable for further investigations (vascular function tests, angiography), in order to able to demonstrate the predominant pathophysiological disorder. The combination or these two diseases may influence the treatment modalities. PMID- 4023081 TI - [The anterior saphenous veins of the thigh]. AB - The authors base their argument on a homogeneous series of 75 patients who, in the course of crossectomies and the stripping of the long saphenousvein carried out by the authors, were given a puncture-phlebectomy of the accessory anterior saphenous vein or veins. Firstly they analyse the clinical characteristics of the incompetence of these veins in the 75 patients. Then, in the discussion, they carry out a closer study of the anterior saphenous veins in the thigh, which have their own anatomical, physiopathological, clinical, and therapeutic characteristics. Without mistaking the role of complementary sclerosis in these cases, they affirm that reliable results are more difficult to obtain with this sort of vein and they suggest peroperative puncture phlebectomy as the results of this seem very encouraging. PMID- 4023082 TI - [Venous ligation in ambulatory patients]. AB - The author here suggests a simple treatment not of the varicose illness but of the main functional symptomatology especially affecting old people, who, too often, are negligent or neglected. By means of a simple ligation, under local anaesthetic, of a long saphenous vein below the saphenofemoral junction, it is possible to achieve the rapid treatment of trophic disorders such as ulceration or major varicose ectasia. The one thing that counts here is the idea of a short term result, and the average three-and-a-half weeks healing time for the ulcers studied attests to this. The indications involve about 2% of the population and apply especially to old people who either refuse to be operated on or wouldn't benefit by surgery. However, this method is still an exceptional therapeutic solution. PMID- 4023083 TI - [A new case of impotence after stripping]. AB - Impotence following venous stripping has been rarely reported in the French of Anglo-Saxon literature. The authors report a new case, which was investigated by means of a full psychological, clinical and paraclinical survey. The aetiology appears to be related to the intra-operative ligation of the external pudendal artery, an hypothesis which has already been proposed, but without any objective evidence. The authors describe, for the first time, a simple and original methodology of selective compression to be performed routinely during Doppler flow studies of the penile arteries, which greatly increases the quality and the reliability of the information obtained. PMID- 4023084 TI - [Ultrastructure of the media and biochemistry of the intercellular substance of the wall of varicose veins]. AB - A description using electronic microscope examinations the ultrastructural modifications affecting myocytes and the intercellular substance of the walls of varicose veins. They also have an effect on the biochemical composition of the intercellular substance. PMID- 4023085 TI - [Bone and vascular injuries of the popliteal fossa. Apropos of 21 cases]. AB - The authors report twenty-one cases of bony and vascular trauma of the popliteal fossa. The first step in the appropriate treatment of these lesions is to be aware of the associations of the two types of lesion, independent of the degree of bony damage; an isolated dislocation may be associated with a sub-adventitial rupture of the popliteal artery. Surgical treatment consists of bony fixation followed by vascular repair, which requires autologous popliteo-popliteal or femoro-popliteal venous by-pass grafts in 90 per cent of cases. This repair should concern both the artery and the vein, as the immediate prognosis depends on the complete repair of both vessels. The immediate results essentially depend on the nature of the traumatic aetiology: gunshot wounds, or motor vehicle accidents, and on the quality of the vascular repair. The long term prognosis depends on the quality of the orthopaedic treatment. In every case, the classical reputation of the severity of such associated lesions is fully justified. PMID- 4023086 TI - [Drug therapy of venous insufficiency]. AB - Venous pharmacotherapy is a subject which, up to now, has not been submitted to rigorous scientific investigation as we currently lack in vivo observation methods. We can oppose direct actions stemming from sympathic stimulation and tissular mediators to the indirect actions of the substances which affect the arteriolar circulation or arterio-venous anastomoses. Anthocyanosides are amongst the most important of all the drugs acting on the permeability of the membrane. Dihydroergotamine, which has revived old controversies about the vegetative innervation of vein walls, has proved to have an increasing effect on venous pressure in clinostatism. We have ourselves witnessed this venotonic action of subjects in the supine position. In an upright position there have not been any reactions of hypertension, perhaps because of the hypertonic effect obtained naturally from the bard receptors which prevail on the pharmacological effect. PMID- 4023087 TI - [Etiopathogenesis and therapy of ulcers of the lower limbs]. AB - The authors assess the pathogenic causes of leg-ulcers which all have as a common denominator chronic venous incompetence. It is vital to have a correct identification of prevention of frequent relapse as well as cure. The authors suggest their strategy of topic treatment which, despite its simplicity and economy, has never proved unsuccessful. PMID- 4023088 TI - [Indications for surgical and sclerosing treatment of varices of the lower limbs]. AB - The authors consider the usefulness of sclerosing varicose veins in the lower limbs according to tournay's classic teaching, and in accordance with their basically surgical orientation, they try to classify a series of absolute indications for the surgical treatment, and a second series of analogous indications for the sclerosant treatment. Since the treatment of varicose veins does not come into effect all at once, the two methods - surgical and sclerosant can be usefully combined. PMID- 4023089 TI - Results of studies of potential light spectrum effects on human performance. PMID- 4023090 TI - In vivo protective effect of beta-carotene against psoralen phototoxicity. PMID- 4023091 TI - Experience with the temporoparietal fascial free flap. AB - The temporoparietal fascia is an ideal tissue source for free transfer to distant sites where ultrathin coverage is either desirable or mandatory. The fascia's dependable vascular anatomy facilitates the technical aspects of microvascular transfer by means of its large vessels, ample pedicle, and ability to be grafted on either side. Furthermore, this highly vascular tissue is available in surprisingly large quantities, and its donor scar is hidden in the hair. The authors have found this flap useful (1) in covering exposed bone and tendon without adding unwanted bulk, (2) in providing thin flap coverage or lining in major facial reconstruction, (3) in covering vital structures such as exposed nerves and vessels, (4) in providing neovascularity both as a recipient graft bed and for control of chronic infection, and (5) in reestablishing gliding-tendon mechanisms. The authors have successfully employed this free flap in 15 cases which involved deformities of the ankle, foot, Achilles tendon, forearm, hand, nose, and contralateral ear and scalp. Seven cases are utilized to illustrate the broad application of this unique and versatile free flap. PMID- 4023092 TI - Esthesioneuroblastoma: treatment of skull-base recurrence. AB - Thirty-nine patients with esthesioneuroblastoma are reviewed. The presentation of the tumor, symptomatology, investigation, and treatment are discussed. A recommended treatment regimen is outlined. Histologic typing is valueless in predicting tumor behavior. An illustrative and difficult case of recurrent base of skull esthesioneuroblastoma is presented. The resection performed is described, and the problem of extradural oropharyngeal communication is discussed. The solution was to use a temporalis and galeal frontalis flap. Reconstruction was with an external and intraoral prosthesis. Optimal treatment in a fresh lesion is radical surgery with or without radiation therapy. Esthesioneuroblastoma is a rare and often misdiagnosed malignant tumor of the olfactory epithelium. Originally described by Bergen et al. in 1924 as "esthesioneuroepithelioma olfactif," it was introduced into the North American literature by Schall and Lineback in 1951. Since then, fewer than 200 cases have been collected. The various terms used to describe it--olfactory esthesioneuroblastoma, esthesioneurocytoma, and olfactory neuroblastoma--all denote origin from the neural crest. The sensory nerves of smell are short bundles of fibers that originate in the olfactory bulb and pass through the cribriform plate to the olfactory area of the nasal mucosa. This mucosa is located in the most superior part of both nasal fossae. Thus the usual primary sites of occurrence include the superior nasal cavity or nasal septum, and turbinates, the ethmoid, or the cribriform plate, although an extranasal site of origin has been suggested. Symptoms are usually progressive and range from nasal obstruction or epistaxis to diplopia, ocular pain, and headaches in the more advanced disease state.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4023093 TI - Trigonocephaly: refinements in reconstruction. Experience with 33 patients. AB - Thirty-three consecutive patients with metopic synostosis treated between January of 1980 and June of 1984 are presented. All patients underwent craniofacial reconstruction by an interdisciplinary team utilizing a detailed remodeling of the supraorbital rims and forehead. Advantages of the current modifications are discussed, as well as an analysis of the results. We believe this represents a significant advance over previous methods not only because of the superior cosmetic results achieved, but also because of its safety and reproducibility. Reoperation rate was less than 10 percent overall and was necessary only in patients with complex cranial vault abnormalities. Mean follow-up was 22.8 months, with no deaths, infections, or damage to visual or cerebral function. Postoperative head circumference demonstrated an immediate increase followed by a normal growth curve. PMID- 4023095 TI - Midline cervical cleft. AB - Midline cervical cleft is a rare congenital anomaly of the ventral neck. A series of 12 cases of midline cervical clefts over a 30-year period is reported. This anomaly is part of a spectrum of midline branchiogenic syndromes resulting from abnormal migration of cells derived from the branchial arches. The preferred operative correction requires complete excision of the cleft with its underlying fibrous cord and closure with multiple Z-plasties. PMID- 4023094 TI - Oblique facial clefts: pathology, etiology, and reconstruction. AB - Modern views on embryology have increased our understanding of the nature of oblique facial clefts. The anomalies that have their origin at the junction of facial processes, such as the nasomaxillary dysplasias, may be named primary clefts or transformation. The maxillary clefts that are due to a developmental arrest of the skeleton are in fact secondary defects of differentiation defects. The teratology of these malformations is discussed, and attention is drawn to the amniotic rupture syndrome as a possible cause. All these clefts are rare, their incidence ranging from 0.75 to 5.4 per 1000 common clefts. This author has been involved in the treatment of nine of these patients. Four had their malformation reconstructed with one of the conventional procedures described in the literature, but the results, although initially acceptable, soon deteriorated. A more aggressive approach was therefore chosen. Rotation and advancement of the cheek proved to be extremely effective and is now advocated as the procedure of choice. The transposition of a median forehead flap is considered an excellent alternative. Use of these procedures in five patients is reported. There were no complications. PMID- 4023096 TI - Speech results after bilateral osteotomy surgery for cleft palate: a review of 413 patients. AB - Patients records of those who had received the bilateral osteotomy surgical procedure for cleft palate were studied. There were 413 records available for review. Patients evaluated by a speech/language pathologist numbered 226. The other 137 patients were evaluated either by a school speech/language pathologist or by the plastic surgeon. An additional 50 records could not be used. Patients were 18 to 24 months through 35 years of age. The results revealed that 81.5 percent of the patients demonstrated normal or near normal resonance quality. Two additional positive aspects of the procedure are that the risk of postpuberty maxillary retrusion is reduced, and palatal length is increased. It is, however, a disadvantage that considerable training and experience are essential in order that the surgeon can successfully use the osteotomy. Based on a review of the literature and findings of this study, it appears that the speech results for bilateral osteotomy palate closure are comparable with and in some cases better than the results reported on smaller populations. PMID- 4023097 TI - The subunit principle in nasal reconstruction. AB - The nasal surface is made up of several concave and convex surfaces separated from one another by ridges and valleys. Gonzalez-Ulloa has designated the nose an aesthetic unit of the face. These smaller parts (tip, dorsum, sidewalls, alar lobules, and soft triangles) may be called topographic subunits. When a large part of a subunit has been lost, replacing the entire subunit rather than simply patching the defect often gives a superior result. This subunit approach to nasal reconstruction causes unsatisfactory border scars of flaps to mimic the normal shadowed valleys and lighted ridges of the nasal surface. Furthermore, as trapdoor contraction occurs, the entire reconstructed subunit bulges in a way that simulates the normal contour of a nasal tip, dorsal hump, or alar lobule. Photographs show five patients in whom this principle was followed and one in whom it was not. PMID- 4023098 TI - Lipoplasty of the neck. AB - Lipoplasty provides a new method of removing subcutaneous fat and contouring the neck. This author reports his experience in 50 cases. A total of 35 patients were done in conjunction with a rhytidoplasty, and 15 patients had lipoplasty as an isolated procedure. The series could be divided into halves. After 25 cases, several undesirable results were noted, including discomfort (15 of 25), nodularity (6 of 25), and contour irregularities (3 of 25). Modifications were made in the technique and postoperative treatment, including a smaller-diameter cannula, more extensive dissection with feathering, multiple incisions and cross tunnels, and the postoperative use of massage and ultrasound and an elastic head garment. Subsequent patients had reduced morbidity and improved operative results. A detailed account of the operative procedure is discussed. Photographic documentation of results is given. This author's initial experience with lipoplasty of the neck indicates early problems, solutions, and results. The technique is viewed as a useful addition to the armamentarium of the plastic surgeon. PMID- 4023099 TI - More than skin deep: a self-consistency approach to the psychology of cosmetic surgery. AB - Underlying attitudes about the general self and the specific body part operated on in cosmetic surgery were investigated. It was hypothesized that female cosmetic surgery patients would feel less favorably toward their noses, faces, or breasts than toward their overall self. These marked inconsistencies would cause "normal" individuals to seek practical solutions of enhancing the esteem of the particular body part, to make it consistent with their general view of themselves. Forty female cosmetic surgery patients were tested before and 2 and 4 months after surgery. In all, 12 hypotheses were made within the general self consistency framework and 11 were upheld at levels ranging from 0.02 to 0.001. Self-consistency theory accurately represents the female cosmetic surgery patient as a normal woman in terms of self-esteem who is attempting to remediate a consciously felt inconsistency between general and specific body-part esteem. Cosmetic surgery seems to reduce this inconsistency. PMID- 4023100 TI - The Achilles heel of plastic surgery: insurance forms, fraud, and loss of credibility. PMID- 4023101 TI - Lack of adverse effect of silicone implant on sarcoidosis of the breast. AB - Involvement of the breast by sarcoidosis is extremely rare, with only 11 case reports in the literature. The potential adverse interaction between silicone prostheses and this disease process poses an unusual clinical dilemma. However, two patients with sarcoidosis of the breast had silicone breast implants placed without exacerbation of their disease nor unusual periprosthetic complications. We conclude that sarcoidosis of the breast does not appear to be a contraindication to placement of silicone implants. PMID- 4023102 TI - Lateral antebrachial cutaneous nerve injury as a complication of phlebotomy. AB - The lateral antebrachial cutaneous nerve may be injured by attempts at cephalic vein venipuncture because of its anatomic location under the cephalic vein. Multiple attempts at venipuncture using plunging-type action should be avoided. Electric dysesthesias during venipuncture should alert the phlebotomist to possible nerve damage. Primary repair of the injured nerve or its fascicles may be hindered by tension across the antecubital fossa when the elbow is in extension or by the presence of the biceps tendon. As an alternative surgical solution, the neuroma may be resected and the proximal end buried within the substance of the brachialis muscle. PMID- 4023103 TI - The hairless osteotomized radial forearm flap. AB - A case is reported demonstrating that the radial osteocutaneous free flap can be "ill-treated" by excision of its hairy skin and split-skin grafting prior to transfer and osteotomy of its bony element during transfer without apparent adverse effect. PMID- 4023105 TI - Interosseous fixation with hemoclips. AB - We report the use of a surgical Hemoclip for the stabilization of a facial fracture. The clip is simple to use and of appropriate strength to hold fracture fragments in anatomic alignment. Its use is not proposed as a substitute for the time-proven techniques, but rather as a potential addition in selected cases to the well-trained facial reconstructive surgeon's armamentarium. PMID- 4023104 TI - Use of suction to treat soft tissue injected with liquid silicone. AB - Suction was used to treat erythema and draining sinuses resulting from injection of liquid silicone to the chin of a 38-year-old female. Erythema disappeared days after surgery, and there has been no evidence of further drainage. The result is shown 2 and 6 months following the surgery. PMID- 4023106 TI - Cleansing eyelids after blepharoplasty. PMID- 4023107 TI - Protecting the eye with the scleral lens during surgery. PMID- 4023108 TI - Pressure sores. PMID- 4023109 TI - [Infant hypotonia, obesity, hypogenitalism and oligophrenia--new viewpoints on the etiology and symptoms of Prader-Willi syndrome]. AB - We present four cases of Prader-Willi syndrome. Two of them have an abnormality of a chromosome 15, the other both show different chromosomal abnormalities. Translocations or deletions were found recently in the bands 15q11/12 in about 60% of the cases of Prader-Willi syndrome. The consequences for diagnosis, symptomatology and genetic counselling of the syndrome are discussed. PMID- 4023110 TI - [Comparative clinicogenetic study of schizophrenic psychoses]. AB - The author diagnoses 350 carefully selected schizophrenic subjects, their parents and their siblings during parallel studies using three different clinical classification systems and analyzes the results by multiple threshold analysis and the multifactorial inheritance model. The results suggest that, of the three classifications the author studied, Leonhard's and Sneshnewski's system yield relatively homogeneous subgroups; this indicates the future significance of these nosological systems for the planning of biopsychiatric research. PMID- 4023111 TI - [Ego function rating by the specialist working alone in neurology and psychiatry]. AB - Bellak and coworkers' "Ego-Function" rating was performed at a neuropsychiatric outpatients department by having an interview that was recorded once on tape analyzed by the same rater at intervals of 16 +/- 6 months using an estimation scale divided into seven main points. The result shows a high degree of uniformity in assessing the following functions: Reality testing, judgement, feeling for reality of oneself and the world, control of drives and affects, relationship to objects, ability to think, use of fantasy for solving problems, protection from stimuli, defence function, autonomic function, synthetic integrative function and feeling of competence. The most important result is that the rating can be used to good effect by neurologists and psychiatrists working alone. PMID- 4023112 TI - [Experiences with the Meyer-Probst encephalopathy questionnaire]. AB - The validity of the questionnaire elaborated by Meyer-Probst for recording the typical behaviour of encephalopaths was checked on a sample comprising 254 high risk and control children aged 6 to 7 years. The results confirm its value as a diagnostic aid in outpatient work and as methodological tool for research. PMID- 4023113 TI - [Group therapy with selected forensic-psychiatric patients (dyssocial maldevelopment]. AB - The treatment of patients with medically relevant dissozial misdevelopment in a forensic-psychiatric clinic demands special methods corresponding to the subjective and objective conditions. The group therapy represents a possibility of activating those patients in a socially adequate way. There are being described the course and first results of this method. PMID- 4023114 TI - [Information status and public opinion on the social psychiatric position of epilepsy in western Lower Austria]. AB - The state of information and the public opinion concerning the epileptic's psychosocial rank in the West of Lower Austria are similar to the results in the Federal Republic of Germany in many respects. But on the other hand there are also many differences. Many of the interviewed ones reacted in the sense of "centrality of concerness". Questions concerning society in general, the answers were liberal and partly even outgoing. When the own persons or the own family got involved answers were significantly less positive than in Western Europe or the USA. Answers concerning employment of epileptics were reflecting the socio economic situation of the different countries at the moment of the interview. If there was a better socio-economic background it also was easier to make a motion for employment of epileptics. The age-group between 30 and 40 years proved to be best informed and most outgoing. PMID- 4023115 TI - [Classic texts newly read. Uninhibited "tallyho" in hunting the "laws" of delirium. Thoughts on rereading K. Conrad "Die beginnende Schizophrenie--Versuch einer Gestaltanalyse des Wahns", Stuttgart (Thieme) 1958]. PMID- 4023116 TI - [Segregation of psychiatrically ill offenders in specialty clinics--the end of the deportation game?]. AB - Forensic psychiatric institutions (mentally ill offenders) have not developed according to the recommendations of psychiatric experts as suggested in the 'Psychiatric Enquete'. Paragraph 65 StGB with its provisions was eliminated from the penal code on the 1. Jan. 1985, hence independent social-therapeutic institutions will not come into existence in the FRG. Taking the current institutional conditions into account the authors investigate the chances and possibilities of client-orientated treatment. PMID- 4023117 TI - [Analysis of a patient population of the neurologic-psychiatric admission department of a central prison hospital]. AB - This article represents an attempt to analyse the multivarious and problematic groups of neurological and psychiatric inpatients admitted to a central hospital for prisoners in Baden-Wurttemberg. This special ward for such patients is unique in its character in the entire Federal Republic of Germany. Patients are differentiated according to diagnosis, length of stay, duration of imprisonment, reason for referral, number of patients referred, and kind of treatment. The four most strongly represented groups of diagnosis consist of the patients with psychogenic reactions, drug addiction, endogenous psychoses and psychopathies. These differ from one another according to treatment regimen, reasons for referral, and mode of hospitalisation. Statistics are given reflecting the problems of non-German, mentally abnormal prisoners and of their suicidal or para suicidal actions. PMID- 4023118 TI - [Fatalities in the course of hospitalization in a psychiatric hospital (paragraph 63 StGb)]. AB - On the average, every tenth proband dies during his compulsory referral to a psychiatric hospital decreed by a court of law. The mortality rate among sentenced persons is not only much higher than that of inmates of a normal prison, but is also much higher than among patients of psychiatric hospitals not compulsorily referred by court. Those who died during hospitalisation, were fully exculpated more often than those who survived at the end of their term; furthermore, they had served their sentences on the average for a longer time than the survivors. The combination of mental disease, legal culpability and imprisonment exercises a particularly dramatic effect on the suicide rate. PMID- 4023119 TI - [Suicide in psychiatric therapy: problem sketch and consequences for forensic psychiatry evaluation]. AB - Suicidal modes of behaviour are discussed in their forensic-psychiatric aspects, and the problems of a typical case are presented as an example. As in other medical disciplines, questions of recognizability and correct treatment of pathological disorders are of particular interest from the legal point of view. The analysis of suicidal modes of behaviour in larger populations can admittedly demonstrate more or less typical patterns, but reliable parameters for individual prognosis are not available. For this reason, suicidal tendencies in the individual are in principle not recognizable. A standard psychiatric therapy with guaranteed success does not exist. We draw attention to the particular responsibility for accurate documentation of each case history. PMID- 4023120 TI - [Behavior therapy of opiate dependence]. AB - Ten years ago an extensive behaviour therapy programme for the treatment of young opiate addicts was developed and tested, and shown through follow-ups extending over a period of two years to be successful. Some of the most important behaviour therapy procedures are introduced. A distinction is made between traditional methods which have been used since the beginning of the therapy programme and newer approaches in behaviour therapy, which in recent years have led to a broadening of the spectrum of therapy. In conclusion important areas for the treatment of opiate addicts in the future are dealt with, which make further improvements in the efficiency of therapy possible. PMID- 4023121 TI - Clinical perspectives on self psychology. AB - With the help of several clinical vignettes from the literature, the clinical consequences of the theoretical system of self psychology are examined. In that system pathogenic primacy is given to failures in parental empathy, leading to the technical requirement of providing empathic responses which build a cohesive self through transmuting internalizations. Efforts to extend the application of self psychology to include the psychoneuroses lead to an interactional reparative therapy that compromises interpretation of transference and resistance. Therapeutic change resulting from this approach is seen as essentially different from the processes and transformations set in motion by classical analysis. PMID- 4023122 TI - Potentiality shrouded: how the newer theories work. AB - An analyst often needs to feel that the integration he anticipates and provokes was already observed, fully present, in the patient. He can feel that way by cultivating an empathic sense that the patient's aspects and movements are inevitable and not chosen. A full theory of the mind, however, describes other possibilities. For that reason, it is sometimes useful to work with incomplete theories that omit descriptions of potentiality. These holistic revisions of psychoanalysis increase the variety of passively perceived treatment-relevant configurations and lessen the analyst's descriptive authority. PMID- 4023123 TI - Isakower-like experience on the couch: a contribution to the psychoanalytic understanding of regressive ego phenomena. AB - Since Isakower's original contribution of 1938, Isakower phenomena have been viewed as primitive experiences involving maternal breast, womb, and face imagery. This clinical report harks back to the less well-known hypothesis with which Isakower concluded his paper: he suggested that these perceptual experiences are related to childhood oedipal masturbatory fantasies at the time of going to sleep. In this paper four Isakower-like phenomena experienced by a patient on the couch are reported in the dynamic context in which they occurred. It is argued that these phenomena constitute a type of regressive ego experience that defends against oedipal conflict. PMID- 4023124 TI - Oedipus complex and development of self. AB - The emergence of oedipal object relations is a crucial stage in the development toward individuated adult mentation, distinguished from early stages of psychic life which are transindividual (as in Kohut's "selfobject transference"). The latter continue to function as deep layers of individual psychic life; but the development of oedipal/postoedipal object relations, and advanced psychic structure and functioning based on it, represents a norm in psychoanalytic psychology and therapy. The poet John Keats's ideas about the formation of the individual "soul" (identity as an individual) by the intervention of "circumstances" are cited to illustrate this aspect of the oedipus complex. PMID- 4023125 TI - Demythologizing oedipus. AB - The oedipus complex is a basic psychoanalytic concept, which is only historically tied to its eponymic myth. It works in our system and in our method as a hermeneutic principle, organizing our understanding of the discourse of patients. Its validity depends on the situation of childhood development within the family, with its attendant passions and desires. PMID- 4023126 TI - Evolutionary psychiatry and the triune brain. PMID- 4023127 TI - Records of psychiatric morbidity in general practice: the National Morbidity Surveys. PMID- 4023128 TI - Depression and dementia: the multi-faceted relationship. PMID- 4023129 TI - Sensitivity to noise in a community sample: I. Measurement of psychiatric disorder and personality. AB - A sample of 77 women of high and low noise sensitivity, living in areas of high and low exposure to aircraft noise drawn from the 1977 West London Survey, were interviewed in the community in 1980. Women of high, intermediate and low noise sensitivity in 1980 were compared for measures of psychiatric disorder, personality and reactivity to the other sensory stimuli. In addition, the noise sensitivity measures defining the three groups in 1980 were compared with further measures of noise sensitivity. High noise sensitive women exhibited significantly more psychiatric symptoms, higher neuroticism scores, and greater reactivity to other sensory stimuli than intermediate and low noise sensitive women. PMID- 4023130 TI - Sensitivity to noise in a community sample: II. Measurement of psychophysiological indices. AB - A sample of 77 women of high and low noise sensitivity in 1977, living in areas of high and low exposure to aircraft noise, were interviewed in the community in 1980. High, intermediate and low noise sensitive women were compared, using measures of blood pressure, heart rate, skin conductance, hearing threshold, uncomfortable loudness level and magnitude estimation of six tones. These physiological measures did not clearly distinguish different noise sensitivity groups, except that highly noise sensitive women had a consistently slower heart rate. Noise sensitivity was not related to auditory threshold. In the high aircraft noise area there were significantly more skin conductance responses than in the low aircraft noise area irrespective of noise sensitivity. This may be the result of chronic exposure to high aircraft noise. PMID- 4023131 TI - The chronically mentally ill in primary care. AB - The role of primary care physicians in addressing the needs of chronically mentally ill patients is examined from three perspectives: assessing community prevalence; treating chronic medical problems in the context of other human service needs; and treating specific types of chronic mental disorders. About 30% of primary care patients were found to have at least one Research Diagnostic Criteria mental disorder, five-sixths of which had a duration greater than 1 year. However, about 9% of patients had some impairment and 2% had severe impairment associated with a mental disorder. Although affective disorders have the highest overall rates, personality, psychotic, and anxiety disorders contribute the greatest proportion of severe disability. PMID- 4023132 TI - An indigenous conceptualization of reactive depression in Trinidad. AB - While depressive reactions appear to be universal, until recently they have seldom been described outside Europe, probably because of their lack of exotic salience, but also because they are seldom identified locally as distinct entities. Where it occurs, such an identification reflects a local preference for the articulation of individual psychological notions, rather than universal moral imperatives. While the symptoms of reactive depression are recognized in rural Trinidad as a common experience, but not especially remarked, they are also identified by Afro-Caribbeans as a specific state, Tabanka, following the loss of a sexual partner to another. Tabanka is characterized by lassitude, anorexia, insomnia, feelings of worthlessness, anger, a loss of interest in work and other activities and, especially, by a preoccupation with the faithless one. It is said to be most common among married men and among the upwardly socially mobile, and to lead to heavy drinking and occasionally madness or suicide. The precipitation of Tabanka provokes hilarity rather than moral indignation, and its humour articulates an egalitarian and individualistic working-class attitude to marriage and social mobility. In contrast, Trinidadians of Asian or Venezuelan origin emphasize moral notions of honour and shame. PMID- 4023133 TI - Social support, social pressures and psychological distress during unemployment. AB - A sample of 1150 unemployed 17 year-olds, containing blacks and whites, males and females, was obtained from 11 urban regions in England. Social support was measured in respect of five different forms of help from others. Measures were also obtained of psychological distress, perceived pressure from others to obtain a job, employment commitment, contact with other young people, and contact with other unemployed young people. Two forms of social support (having someone to turn to for help with money, and having someone to suggest interesting things to do) were significantly associated with measures of distress, as were perceived pressure to obtain a job and employment commitment, but not contact with other unemployed young people. The association between distress and having someone to turn to for help with money was greater for those perceiving pressure from others to obtain a job than those not perceiving pressure. Also, the association between distress and having someone to turn to when feeling low was greater for those with a high employment commitment than for those with a low one. Other associations between support and distress were found to be affected by sex and ethnic differences in the sample. The results are discussed in the light of a stress-buffering model of social support; and the need to disaggregate social support into its component parts is emphasized. PMID- 4023134 TI - Some cognitive correlates of affective disorders. AB - Seventy-one men completed a battery of cognitive tests which were designed to reflect verbal analytic and non-verbal holistic functioning. Interest centred around pattern of response. Thirty men were suffering from an affective disorder and forty-one were well. All the men were in prison, the majority awaiting trial. The affective disorder group was subdivided into three categories: men who had a history of manic-depressive illness; a group of unipolar, psychotically depressed men; and men who were regarded as being depressed in reaction to circumstances. All three groups showed specific difficulty in dealing with spatial/holistic tasks, other factors being held constant. They were also found to differ in a number of other respects. The possible significance of these differences is discussed. PMID- 4023135 TI - Description and measurement of concentration problems in depressed patients. AB - Depressed patients commonly complain of concentration problems, yet these have seldom been the focus of systematic investigation. A structured interview about concentration problems was administered to a group of relatively severely depressed patients. Problems in reading and watching television were the most common, and were highly correlated with each other. Direct report of the number of concentration lapses on a reading task was the most generally satisfactory task-performance correlate of complaints of reading/TV concentration problems. Evidence both from this task and from the interview suggests that depressive concentration problems may often be due to 'mind-wandering'. The correlations with concentration problems with the severity and endogeneity of depression and with state anxiety were generally similar. PMID- 4023136 TI - Personality traits and platelet monoamine oxidase in tobacco smokers. AB - A study was made of the smoking habits of an unselected series of 1129 18-year old men from the general population. Their smoking habits were related to personality traits, intellectual level and platelet monoamine oxidase (MAO). Regular smokers were found to be extraverts, sensation seekers who were easily bored and with a strong tendency to avoid monotony. They also had a lower than average intellectual level, and were more prone to the abuse of alcohol, glue, cannabis, amphetamine and morphine. Furthermore, they had a low platelet MAO. The results are discussed in relation to the pharmacological reasons for smoking and favour the hypothesis that tobacco smoking is related to arousal-seeking behaviour. Ex-smokers had personality traits, intellectual levels and platelet MAO of the same magnitude as non-smokers: this may be the reason why they were able to give up smoking. PMID- 4023137 TI - Carotid endarterectomy: does it improve cognitive or motor functioning? AB - In a group of 20 patients who were to undergo endarterectomy for atherosclerotic occlusive disease of the internal carotid artery, the stenosis did not appear to have resulted in cognitive or motor deficits. Consistent with this finding, surgery could not be shown to have a beneficial effect on cognitive or motor functioning. Control data were supplied by 20 patients who underwent peripheral vascular surgery and 20 healthy subjects. The test-retest interval was 10 weeks. PMID- 4023138 TI - Food antibodies in acute psychoses. AB - Antibodies to a variety of foods, and in particular cereals, were measured in serum from 100 patients with acute psychoses and 100 elective surgical patients. For 13 out of 14 foods to which non-IgE antibodies were detected the schizophrenics had slightly more antibodies than the controls. There was an association between a possible secondary mania and the presence of IgE antibodies to wheat or rye. However, neither the schizophrenia nor the mania findings can be regarded as evidence for food allergy causing psychiatric disorder, since the immunological findings in both cases may represent consequences of the illnesses or their treatment, rather than causes of the illness. PMID- 4023139 TI - Side-effects of lithium at lower therapeutic levels: the significance of thirst. AB - The prevalence of thirst, subjective polyuria and related side-effects was investigated in 87 patients attending a lithium clinic and in a group of 52 controls. Thirst was surprisingly common, occurring in 67% of patients, in spite of the fact that they had been maintained on relatively low levels of lithium, and was due principally to the lithium rather than to other psychotropic drugs. Urine flow and impaired renal water absorption correlated with the serum lithium level and the length of treatment in the patients, despite the fact that few were clinically polyuric. The pattern of the results confirms previous suggestions that lithium may stimulate the thirst mechanism directly as well as via an increased renal resistance to vasopressin. The possible implications in terms of clinical response are discussed. PMID- 4023140 TI - Investigating renal function during lithium treatment. AB - The tests that have been used to assess glomerular and tubular function in patients receiving treatment with lithium have been reviewed. The advantages and disadvantages of these are discussed. The most useful tests are the creatinine clearance, which may be predicted from the serum creatinine using a formula or nomogram, and the measurement of urine osmolality, followed if necessary by assessment of the maximum urine concentrating ability after desamino cys-1-8-D arginine vasopressin. PMID- 4023141 TI - Psychiatric patients who marry each other. AB - Health care workers often advise patients with chronic psychiatric disability against marrying each other. A survey of a group of such marriages revealed no evidence of the predicted ill-effects, but rather a trend towards improvement after the marriage. There is a discrepancy between professional expectations and actual outcome of these marriages. PMID- 4023142 TI - Measuring the burden of psychiatric illness on the family: an evaluation of some rating scales. AB - The gradual shift towards non-institutional treatment for severe and chronic psychiatric illnesses has been accompanied by a recognition of potentially harmful effects ('burden') upon the patient's caregivers. This paper aims to provide a framework for the development of further research into the burden of 'community care' by offering a clear definition of the burden concept, an exposition of the criteria for evaluating rating scales to measure the concept, a review of major rating scales of burden, and some suggestions for improvements in methodology which are urgently required. PMID- 4023143 TI - A study of variables associated with under-attendance at a psychiatric day centre. AB - This study examines the problems of client under-attendance at a psychiatric day centre. Demographic, psychiatric, psychometric and Semantic Differential measures were used. Several of these measures were significantly associated with under attendance. Various methods are suggested for the identification of and reduction of the level of under-attendance. PMID- 4023144 TI - A study of the classification of mental ill-health in general practice. AB - An outline is provided of an experimental study of the classification of mental ill-health presented to general practitioners (GPs). Videotaped real-life consultations were assessed by 27 GPs for the purpose. A high degree of inter observer variation was recorded. Some of the implications of the findings are discussed. PMID- 4023145 TI - Validation of the Italian version of the GHQ in a general practice setting. AB - The 30-item General Health Questionnaire (GHQ) and the Clinical Interview Schedule (CIS) were administered to 120 consecutive attenders at a general practice in Northern Italy run by a doctor who had a formal psychiatric training. The Italian versions of both the GHQ and the CIS were found to be feasible instruments for general practice studies in Italy. GHQ misclassification rates, sensitivity and specificity values are presented for different cut-off scores, a total score of 5 or more being the best discriminator between 'cases' and 'non cases'. The prevalence of confirmed cases in this sample was 47.5%, a rate higher than those reported so far in developed and developing countries. PMID- 4023146 TI - The role of theories in conceptual coherence. PMID- 4023147 TI - A social-cognitive theory of depression in reaction to life events. PMID- 4023148 TI - Semantic, evaluative, and self-referent processing: memory, cognitive effort, and somatovisceral activity. PMID- 4023149 TI - The role of the orienting response in the anticipation of information: a skin conductance response study. PMID- 4023150 TI - Mathematical models of the event-related potential. PMID- 4023151 TI - Electrodermal discrimination of familiar and unfamiliar faces: a methodology. PMID- 4023152 TI - The development of sustained visual attention in infants from 14 to 26 weeks of age. PMID- 4023153 TI - Scoring criteria for response latency and habituation in electrodermal research: a critique. PMID- 4023154 TI - Evidence of a role for response plans and self-monitoring in biofeedback. PMID- 4023155 TI - Effects of age and sex on the endogenous brain potential components during two continuous performance tasks. PMID- 4023156 TI - The standardized mental stress test protocol: test-retest reliability and comparison with ambulatory blood pressure monitoring. PMID- 4023157 TI - The Bayesian-inferential approach to defining response processes in psychophysiology. PMID- 4023158 TI - Cardiac awareness in infarct patients and normals. PMID- 4023159 TI - Groin skin temperature: testing the validity of a relatively unobtrusive physiological measure of psychosexual arousal. PMID- 4023160 TI - Cortisol excretion during the defense reaction in humans. AB - Twelve subjects with specific phobias were exposed to slides with a phobic or a neutral content while cortisol excretion, electrodermal activity, and distress ratings were studied. Six subjects fearful of blood and mutilation, and six of snakes or spiders, were presented with two sets of ten different slides (phobic or neutral; 8-sec exposures, separated by 50-sec intervals) with the order of presentation balanced between days. Before and after each session, subjects rated feelings of distress, and urine samples were obtained for the determination of cortisol by radioimmunoassay. Electrodermal activity was recorded before and during slide presentation. Compared to neutral exposures, phobic slides elicited larger cortisol excretion, higher distress ratings, and greater skin-conductance responses with slower recovery. No differences between animal and blood and mutilation phobics were observed. Thus, humans having specific phobias exhibit pituitary-adrenal cortical arousal during the defense reaction elicited by slides of their phobic objects. PMID- 4023161 TI - Testosterone and cortisol levels in crewmen of U.S. Air Force fighter and cargo planes. AB - Serum levels of cortisol and testosterone were measured in 39 United States Air Force personnel on active duty flying status. The subjects selected belonged to one of the following categories: pilot of a fighter-type aircraft, nonpilot on a fighter plane, pilot of a cargo-type aircraft, or nonpilot on a cargo plane. Blood samples were taken prior to and after a routine flying mission. Cortisol levels prior to the flight did not differ across groups. However, postflight samples of cortisol were elevated in the nonpilots, in comparison to the pilots, regardless of aircraft type. Conversely, while testosterone levels were unaffected by crew position, the men flying on fighter-type planes had lower serum levels than did those on cargo planes. These results suggest that hormone levels may be differentially affected by the stressors of routine military flight. PMID- 4023162 TI - Androgen enhances sexual motivation in females: a prospective, crossover study of sex steroid administration in the surgical menopause. AB - Various parameters of sexual functioning were assessed in a prospective, crossover investigation of 53 surgically menopausal women. Patients randomly received either an estrogen-androgen combined preparation, an estrogen-alone drug, an androgen-alone drug, or a placebo. Also included were a group of women who had undergone hysterectomy and whose ovaries had been left intact. Two treatment phases, each of 3 months' duration, were separated by an intervening placebo month. Additionally, plasma levels of total estrogens and testosterone were assayed four times during the study concurrent with monitoring of sexual behaviors. It was clear that exogenous androgen enhanced the intensity of sexual desire and arousal and the frequency of sexual fantasies in hysterectomized and oophorectomized women. However, there was no evidence that testosterone affected physiologic response or interpersonal aspects of sexual behavior. These findings suggest that the major impact of androgen in women is on sexual motivation and not on sexual activity per se. PMID- 4023163 TI - The menstrual cycle and platelet 5-HT uptake. AB - The association between the onset of depressive illness and the paramenstruum has been reported. In the present study, we looked at changes in platelet 5-HT uptake in six healthy, regularly menstruating subjects on days 1, 10, and 24 of three consecutive menstrual cycles to explore possible biochemical bases for mood changes associated with menstruation. Platelet 5-hydroxytryptamine (5-HT) uptake was determined by suspension of platelet pellets in 0.5-5 microM hydroxy [G-3H] tryptamine [( 3H]-5-HT) creatinine sulfate solution at 37 degrees C and measurement of radioactivity of [3H]-5-HT in the platelets using liquid scintillation counting. Mood changes were measured using the Moos Menstruation Distress Questionnaire and the Spielberger State Anxiety Scale. Analysis of variance and trend analysis revealed significant elevation of Km and Vmax on day 24 of the cycle, which was consistent across the three menstrual cycles studied. A significant linear rise of "negative affect" across each cycle peaking on day 1 was detected. "Water retention" and "behavioral change" also peaked on day 1. No significant correlation, however, was obtained between the mood scores and platelet 5-HT uptake. These findings are discussed. PMID- 4023164 TI - The salience and timing of the menstrual flow. AB - The relationship of two menstrual characteristics-flow and length-to reported menstrual symptomatology, attitudes, and effects upon performance were examined in a sample of 156 college women. The possible effects of social contextual variables in mediating this relationship were also explored. Perceiving oneself to be irregular was related to performance decrements, menstrual pain, and negative attitudes but not to premenstrual negative affect. Reporting heavier flows was related to more severe symptom reports, activity restrictions, and negative attitudes. Religious group membership affected these relationships, as Catholic women reported more irregular cycles than Protestant women. Reports of heavy flows were related to the importance of religion, symptom severity, and performance decrements in the Catholic but not in the Protestant sample. Possible explanatory models for these results are presented. PMID- 4023165 TI - Psychologic stress and glycemic control: a comparison of patients with and without proliferative diabetic retinopathy. AB - Using a case/control design, patients with (cases) and without (controls) proliferative diabetic retinopathy were compared using three psychosocial measures: life events, psychiatric symptomatology, and ego development. Cases reported significantly more symptoms. They also demonstrated a modest and significant correlation of negative life events with HgbA1c that was not shown in the controls. When the relationship of life events with glycemic control was explored in cases of varying durations of proliferative retinopathy, we found that the association between negative life events and HgbA1c was accounted for by the cases with a recent onset of retinopathy. Patients in this recent group showed a trend towards more negative life events that decreased with longer duration of proliferative retinopathy. This study suggests that the onset of proliferative retinopathy portends a life crisis during which metabolic control is sensitive to additional life stress and that this association is not found among patients whose illness is more stable. PMID- 4023166 TI - Facial expressions of emotion and physiologic reactions in children with bronchial asthma. AB - Eighteen children with bronchial asthma (ages 7.5 to 12) and 18 control children were exposed to a pleasant comic film and a stress-inducing achievement task. Facial expressions of emotion and heart rate (HR) were recorded, and pre- and posttest forced expiratory volume at 1 sec (FEV1) were assessed. The asthmatic children showed significantly fewer expressions of emotion than the control subjects in the stress-inducing but not in the joy-inducing situation. Their FEV1 decreased significantly under both experimental conditions, whereas no significant changes were found in the control group. The asthmatic children's mean HR was significantly higher under both experimental conditions than during the preceding pauses. In the control group, no significant changes in mean HR were found from the pause to the stressful situation; during the comic film, mean HR was significantly lower than during the preceding pause. No significant correlations were found for either group between number of emotions expressed, pre- to posttest changes in FEV1, and changes in mean HR. PMID- 4023167 TI - Hyperparathyroidism: neuropsychiatric manifestations. PMID- 4023168 TI - Carotid endarterectomy. PMID- 4023169 TI - Concurrent myelodysplasia and lymphoproliferation: a disorder of the true pluripotential stem cell? AB - The lymphoproliferative disorders and the myelodysplastic syndromes are thought to result from the clonal expansion of a single abnormal precursor cell. Seven patients who were found to have concurrent myelodysplasia and lymphoproliferation are described. In all cases myelodysplasia and lymphoproliferation were diagnosed simultaneously or myelodysplasia preceded overt lymphoproliferation by a brief interval. Thus, myelodysplasia in these patients was not related to treatment given for a lymphoproliferative disorder. Stem cell theory is reviewed with special reference to evidence for an adult human stem cell common to both haemopoietic and lymphoid cell lines (CFU-L-M). The presence of concurrent myelodysplasia and lymphoproliferation in these seven patients may be the result of the clonal expansion of an abnormal pluripotential stem cell. It may be possible in some cases to achieve remission of the lymphoproliferative disorder with return of normal haematopoiesis if residual normal stem cells are present and repopulate the marrow following cytotoxic therapy. PMID- 4023170 TI - Glycosylated albumin and glycosylated proteins: rapidly changing indices of glycaemia in diabetic pregnancy. AB - Serial measurements of glycosylated albumin (GAlb), glycosylated plasma proteins (GPP) and glycosylated haemoglobin (GHb) were performed by affinity chromatography throughout the course of pregnancy in 14 insulin-dependent diabetic women. In patients whose glycaemic control improved markedly during pregnancy, the concentrations of GAlb and GPP decreased by more than 50 per cent after four weeks of good diabetic control. By contrast, the rate of decrease in GHb levels in the same patients was significantly less and did not indicate a comparable improvement in glycaemia until 12 weeks after good diabetic control was established. Elevated concentrations of GAlb or GPP decrease much more rapidly than GHb concentration when diabetic control is improved; thus measurement of glycosylated proteins is a valuable adjunct to serial blood glucose monitoring in clinical circumstances such as diabetic pregnancy, where early confirmation of good diabetic control is important. PMID- 4023171 TI - Systemic lupus erythematosus and infection: a controlled and prospective study including an epidemiological group. AB - An epidemiological group of 60 SLE patients was studied; 162 infections were observed prospectively for an aggregate of 1366 months. Bacterial infection was more frequent in the SLE patients than in matched controls but only slightly more frequent than in matched rheumatoid arthritis patients. The rheumatoid arthritis patients, also matched with regard to corticosteroid dosage, showed a tendency towards an increased infection rate only. Lower urinary tract infections were comparable in all three matched groups. In a total of 102 SLE patients studied, including the epidemiological group, clinical SLE activity was accompanied by an increase in the frequency of bacterial infection. In 49 patients bacterial infections were more common after flare than before. There was a high incidence of mucocutaneous infections induced by S. aureus, where skin traumatisation was an added risk factor. No increase of opportunistic infections was found in matched groups, but 26 such infections occurred in the subjects as a whole, and they were seen to be more frequent in conjunction with steroid-treated active SLE. Admission to hospital because of suspected infection was common, and infection was the cause or a contributory factor in five of the seven deaths among SLE patients. PMID- 4023172 TI - Parathyroidectomy in chronic renal failure. AB - In order to establish whether parathyroidectomy altered the natural history of ectopic calcification in patients with renal failure we undertook a detailed analysis of 62 patients with hyperparathyroidism secondary to chronic renal failure who were submitted to parathyroidectomy. Biochemical data (61 patients) and radiological skeletal surveys (42 patients) were studied before and after parathyroidectomy. Transiliac bone biopsies were obtained at (or some time in the previous six months before) parathyroidectomy in 30 and in 36 patients after surgery. Paired bone biopsies were available from 17 of these patients. In the majority of patients secondary hyperparathyroidism was controlled after parathyroidectomy although in seven patients (11 per cent), who underwent subtotal parathyroidectomy, it relapsed after initial improvement. Non-visceral soft tissue calcification disappeared or decreased in 60 per cent of the patients after parathyroidectomy. However, despite marked improvement in subperiosteal erosions and histological osteitis fibrosa, with significant reductions in iPTH and Ca X P product after parathyroidectomy, small peripheral arterial calcification developed or progressed in 56 per cent of the patients. Histological osteomalacia after parathyroidectomy developed after operation in two patients. Both had positive aluminium stains for excess aluminium in their bone. Numbers of osteoclasts and the amount of marrow fibrosis declined in parallel following parathyroidectomy, but woven bone persisted for months or years. PMID- 4023173 TI - Are glycosyltransferases the evolutionary antecedents of the immunoglobulins? AB - The glycosyltransferases may be the evolutionary precursors of the immunoglobulins, although critical evidence for this hypothesis is not yet available. The transferases add sugars to non-glycosylated proteins, lipids, and organic molecules, as well as to oligosaccharides, glycoproteins, and glycolipids. The enzymes are specific, extremely polymorphic, occasionally inducible, and may be structurally related to one another. Circumstantial evidence links the transferases to both the MHC and T/t loci in the mouse. Finally, antibodies against purified transferases are difficult to produce and sometimes they react with immunoglobulins. The present hypothesis predicts that transferases should show some sequence homology with immunoglobulins, and that some MHC proteins will be glycosyltransferases. PMID- 4023174 TI - Effects of 20-MHz radiofrequency radiation on rat hematology, splenic function, and serum chemistry. AB - In this study, Sprague-Dawley rats were exposed in a TEM chamber to 20-MHz (HF band) continuous-wave radiofrequency radiation (RFR) for 6 hr/day, 5 days/week up to 6 weeks. The average E-field intensity was 2686 +/- 164 V/m (mean +/- SD) and the calculated specific absorption rate was 0.3 W/kg. Randomly sampled rats killed on Days 8, 22, 39, and 42 after initiation of exposure showed no statistically significant differences from controls for body mass, spleen cell density, erythrocyte and leukocyte counts, hematocrit, hemoglobin, methemoglobin, erythrocyte fragility, bilirubin, creatinine, SGPT, alkaline phosphatase, calcium, sodium, potassium, and spleen cell chemiluminescence. Splenic mass differences were statistically significant (p less than 0.05) only on Day 22. Spleen to body mass ratios differed significantly between exposed and control groups on Days 22 and 39 (P less than 0.05 and P less than 0.025, respectively). Histologic examination of the rats revealed the successive accumulation of phagocytic cells, lymphoid proliferation, development of lesions, and tissue necrosis characteristic of respiratory mycoplasmosis. In a followup experiment, a separate set of rats was exposed for 6 weeks to identical levels of RFR. No significant differences were found in splenic parameters and spleen cell peroxidative activity. Histologic examination of these animals revealed no evidence of mycoplasma infection. The observed differences between exposed and control animals of the first experiment appear to have resulted from subclinical respiratory mycoplasmosis rather than exposure to RFR. PMID- 4023175 TI - 16,16-Dimethyl prostaglandin E2 induces radioprotection in murine intestinal and hematopoietic stem cells. AB - Exogenous prostaglandins (PGs) have been shown to protect gastrointestinal mucosa, liver, and pancreas from several injurious agents, including the PG inhibitor, indomethacin. Previous studies from this laboratory showed exogenous administration of 16,16-dimethyl (dm) PGE2 also protected mouse intestinal stem cells from radiation injury. The present study extended that observation and demonstrated that PGs given to B6D2F1 mice 1 hr before irradiation increased the shoulder of the intestinal clonogenic cell survival curve. The D0 increased from 1.10 + 0.09 to 1.58 + 0.10 Gy. PGs increased the LD50/6 from 16.3 + 0.41 (95% confidence limits) in controls to 20.25 + 0.55 Gy. The 16,16-dm PGE2 increased the hematopoietic CFU-S survival in a qualitatively similar way; the extrapolation number (n) was increased from 1.03 (0.89-1.20) to 1.40 (1.27-1.54) and the D0 increased from 0.92 (0.87-0.98) to 1.14 (1.10-1.19) Gy. A large number of human tumors secrete a variety of PGs. Our results suggest that those tumors may be, in part, protected from radiation injury. PMID- 4023176 TI - Dose-rate evidence for two kinds of radiation damage in stationary-phase mammalian cells. AB - Survival based on colony formation was measured for starved plateau-phase Chinese hamster ovary (CHO) cells exposed to 250 kVp X rays at dose rates of 0.0031, 0.025, 0.18, 0.31, and 1.00 Gy/min. A large dose-rate effect was demonstrated. Delayed plating experiments and dose response experiments following a conditioning dose, both using a dose rate of 1.00 Gy/min and plating delays of up to 48 hr, were also used to investigate the alternative repair hypotheses. There is clearly a greater change in survival in dose-rate experiments than in the other experiments. Thus we believe that a process which depends on the square of the concentration of initial damage, and which alters the effect of initial damage on cell survival is being observed. We have applied the damage accumulation model to separate the single-event damage from this concentration dependent form and estimate the repair rate for the latter type to be 70 min for our CHO cells. Use of this analysis on other published dose-rate studies also yields results consistent with this interpretation of the repair mechanisms. PMID- 4023177 TI - The effects of cellular glutathione elevation on the oxygen enhancement ratio. AB - The radiation responses at various oxygen tensions were evaluated in V79 Chinese hamster cells under conditions where their nonprotein thiols, primarily glutathione (GSH), were elevated by 2-oxothiazolidine-4-carboxylate (OTZ). OTZ, when cleaved by intracellular oxoprolinase, provides the cell with cysteine which stimulates GSH synthesis. A 2-hr pretreatment with 10 mM OTZ elevated GSH to 200% of controls. This elevation in GSH offered no protection to aerated cells; however, for O2 tensions less than or equal to 40,000 ppm modest protection was observed as evidenced by an increase in oxygen enhancement ratio. GSH elevation afforded maximal protection between 1000 and 10,000 ppm O2; however, the extent of protection was relatively small (protection factor = 1.3). PMID- 4023178 TI - Dose response of Langerhans cells in mouse footpad epidermis after X irradiation. AB - Effects of a range (2-50 Gy) of single doses of 250 kV X rays on epidermal Langerhans cells in vivo were quantified in groups of CBA/CaH mice. Animals were sacrificed and compared with controls on the 10th day after local irradiation of their hind feet, when Langerhans cell numbers were at a minimum. ATPase-positive Langerhans cells in sheets of footpad epidermis were counted by light microscopy and cells with Birbeck granules were enumerated by electron microscopy. Both methods revealed a dose-dependent loss of Langerhans cells after ionizing radiation. Fifty percent of the ATPase-positive cells were lost after 14.4 +/- 1.3 Gy, and 50% of Birbeck granule-containing cells were lost after 17.9 +/- 4.2 Gy, suggesting that differentiated epidermal Langerhans cells are radioresistant. Loss of equivalent proportions of ATPase-positive and ultrastructurally identifiable cells after a range of doses indicates that X rays do not merely alter Langerhans cell surface markers but actually deplete the epidermal population of these cells. PMID- 4023179 TI - Microwave-stimulated drug release from liposomes. AB - Microwaves (2450 MHz) are shown to stimulate the release of an aqueous chemotherapeutic drug from phospholipid vesicles. This effect occurs at temperatures below the membrane phase transition temperature of 41 degrees C where these liposomes are normally not leaky. In buffered saline, microwave exposure (60 mW/g) triggers the onset of drug release at 33 degrees C, whereas in plasma a near maximal release is observed as low as 27 degrees C. Significantly, this drug release is enhanced by oxygen and is attenuated by antioxidants. These results demonstrate that phospholipids in artificial membranes devoid of protein are influenced by nonionizing electromagnetic radiation, and that this interaction can be modulated by two physiologically important factors, plasma and oxygen. Such a permeability effect may provide a means for investigating microwave interactions with ordered membrane bilayers. PMID- 4023180 TI - Thermal sensitivity of endothelial cells. AB - Experimental work indicates that one of the mechanisms of tumor control by hyperthermia may be damage to blood vessels, resulting in decreased blood flow to the neoplasms. Among the various elements of the microvasculature, endothelial cells are the most important possible targets of thermal injury. Furthermore, neoplasms have a significantly higher proportion of proliferating endothelial cells than do normal tissues. Thus it is necessary to establish the thermal sensitivity of endothelial cells and to explore possible differences in response between resting and proliferating endothelium. We studied the in vitro thermal sensitivity of murine and human capillary endothelial cells compared to human fibroblasts by following cell survival and growth recovery. Nonstimulated endothelial cells are more sensitive than fibroblasts. Their sensitivity is dose dependent within the range of 42 to 45 degrees C/30 min. Stimulation to proliferate by endothelial cell growth factor (ECGF) renders these cells even more sensitive. Morphologic studies confirm these thermal effects in endothelial cells and fibroblasts. These findings support a direct effect of hyperthermia on endothelial cells, which appears to be more severe in proliferating cells. This may explain the reduced blood flow in heated tumors and may indicate a valuable therapeutic gain for hyperthermia. PMID- 4023181 TI - Effect of dose rate on the induction of experimental lung cancer in hamsters by alpha radiation. AB - The effect of dose rate on the induction of lung cancer in Syrian hamsters by 5.3 MeV alpha particles was examined by varying the number of weekly intratracheal instillations of carrier-free 210Po. By this technique, most of the radiation dose to the lungs was delivered over intervals ranging from 10 to 120 days. Protraction of exposure over 120 days was slightly more carcinogenic at lower total lung doses (24 rad), but slightly less carcinogenic at higher doses (240 rad), than exposure limited to a 10-day interval. No synergism was observed between very low radiation exposures (2.4 rad) and simultaneously administered benzo[a]pyrene. The carcinogenic effect of a single intratracheal instillation of 210Po in isotonic saline was markedly enhanced by subsequent weekly instillations of 0.2 ml of saline alone, emphasizing the importance of noncarcinogenic secondary factors in the expression of radiation-induced lung cancer. PMID- 4023182 TI - [Chromatin degradation during the exposure of thymus lymphocytes in vitro to differentiation inducers and gamma irradiation]. AB - Chemical inductors of differentiation were shown to cause chromatin degradation in thymus lymphocytes. This process was prevented by the protein synthesis inhibitors. The fragments formed after the effect of chemical differentiation inductors on thymocytes were fully identical to chromatin internucleosome degradation products formed in the exposed cells. Chromatin degradation under the effect of chemical differentiation inductors was most pronounced in a more radiosensitive thymocyte fraction. PMID- 4023183 TI - [Effect of irradiation and chemical differentiation inducers on the survival of thymus lymphocytes in mice]. AB - Chemical inductors of differentiation were shown to produce a cytotoxic effect on thymus cells. The protein synthesis inhibitors prevented this effect. The toxic action of the inductors was more pronounced in a most radiosensitive thymocyte fraction. A combination of differentiation inductors and ionizing radiation did not produce the additive effect. This was observed after the effect of radiation and substances being not the differentiation inductors but toxic for cells. PMID- 4023184 TI - [Mechanisms of the synergistic action of ionizing radiation and hydrogen peroxide on the viability of bacteria]. AB - The combined effect of ionizing radiation and minor concentrations of hydrogen peroxide (0.1-0.01 M) has been studied on bacteria differing in the cell wall structure (Gy+, Gy-), radioresistance, and activity of DNA repair system. The H2O2 concentrations applied, which have a slight antibacterial action, enhance significantly the bactericidal effect of ionizing radiation producing a synergistic effect due to the decreased effectiveness of repair of DNA single strand breaks. PMID- 4023185 TI - [Combined use of metronidazole and short-term hyperglycemia during radiation therapy of tumors in rats]. AB - A simultaneous combined treatment with metronidazole and short-term hyperglycaemia, in contrast to application of each of these agents alone, enhanced considerably the therapeutic effect of radiation (a single and fractionated exposure). This was indicated by the increased rate of tumor regression, the number of animals with transient remission, and the number of cured animals which exhibited no relapse throughout the entire 90-day period of observation. PMID- 4023186 TI - [Dynamics of the early ultrastructural changes in sensorimotor cortical neurons of the rat brain after exposure to high doses of gamma-neutron radiation]. AB - At early times (15 min to 6 h) after whole-body gamma-neutron irradiation of mature rats with a dose of 10 Gy reactive changes occur in neurons of the sensimotor cerebral cortex which can be interpreted as a manifestation of the enhancement of functional and metabolic activity of nerve cells followed by inhibition thereof. PMID- 4023187 TI - [Distribution of DNA radiation damage throughout the cells and its comparison with cytogenetic injury]. AB - The distribution of DNA lesions induced by irradiation of Chinese hamster fibroblast cells with different doses was determined by the cytochemical method in situ and compared with the number of cytogenetic damages caused by the same doses. The results obtained indicate that not all the DNA lesions but only those occurred in the structurally important chromosome sites initiate chromosome mutagenesis. PMID- 4023188 TI - [Chromatin breakdown in the white blood cells of rats during irradiation and in combined radiation injury under cystamine protection]. AB - The polydeoxyribonucleotide (PDN) level in leukocytes of peripheral blood of rats treated with cystamine adequately reflects the severity and outcome of radiation sickness. Preventive application of cystamine against the combined effect of ionizing radiation and heat decreased the PDN level in white blood cells but did not influence the survival of animals. PMID- 4023189 TI - [Quantitative and qualitative changes in the peripheral blood cells of rats in chronic irradiation of the animals]. AB - A study was made of qualitative and quantitative changes in peripheral blood lymphocytes of rats subjected to continuous totalbody gamma-irradiation at dose- rates from 0.002 to 0.35 Gy/day and cumulative doses from 0.7 to 20.0 Gy. After termination of irradiation (on the 400th-500th day), the number of lymphocytes changed in an undulatory manner, i. e., increased at a dose--rate of 0.008 Gy/day, and decreased down to minimum control values at a dose--rate of 0.35 Gy/day, and the fraction of young macrocellular forms increased. The effect increased with increase in dose--rate and cumulative dose. PMID- 4023190 TI - [Postradiation effect of a radioprotector depending on the degree of chromatin condensation in the cells]. AB - It was shown on HeLa cells synchronized in mitosis and on rat liver hepatocytes in G0 stage that cysteamine administered after gamma-irradiation produced the radioprotective effect which was not observed in hepatocytes in G1 stage. PMID- 4023191 TI - [Effect of ionizing radiation on the lipid fatty acid composition of the plasma membranes of liver cells]. AB - Changes in the fatty acid composition of total lipids and individual phospholipids of liver cell plasma membranes of intact and exposed (7.65 Gy) rats have been studied. The authors discuss the relationship between the degree of lipid oxidation and other lipid characteristics of the studied membrane after exposure to ionizing radiation. PMID- 4023192 TI - [Chromosome structural damages to the myelokaryocytes of rats in late periods after chronic exposure to tritium and external gamma irradiation]. AB - A pronounced variation in the total amount and spectrum of chromosome aberrations of rat myelocarycytes was found at later times following long-term exposure to tritium oxide and external gamma-radiation (137Cs). Cells with atypical chromosomes (symmetrical exchanges) were 1.5-2 times more frequent in bone marrow of tritium-treated rats throughout the entire lifetime. PMID- 4023193 TI - [Function of the hematopoietic system in irradiated animals prophylactically administered 2-amino-2-thiazoline]. AB - The effect of 2-amino-2-thiazoline (2-AT) on radiosensitivity of mice, their haemopoietic system status, and GFUc has been studied. 2-AT was shown to contribute to the survival of an increased number of haemopoietic stem cells, earlier recovery of bone marrow cellularity, and normalization of the spleen weight. PMID- 4023194 TI - [Plutonium-239 distribution in the body in relation to the rhythm of administration of an iron preparation]. AB - A study was made of the dependence of plutonium distribution among organs and tissues on the time of administration of iron preparation. Iron decreased the share of plutonium in bone tissues, somewhat increased it in soft tissues, and enhanced the excretion of the radionuclide from the organism. The protective efficiency of the preparation in relation to bone tissue was associated with the time of the administration thereof. PMID- 4023196 TI - [Statistical aspects of the relation of the radioprotective action of mercaptoethylamine derivatives and analogs to their electron parameters]. AB - Numerous S-containing substances were used to study the radioprotective efficiency of the preparations depending on their microscopic characteristics. The method of statistical comparison of the qualitative parameters was used to show that the energy parameters were the most informative electron characteristics of the molecules. Each of these parameters correlated with the physicochemical processes induced in a biological system by ionizing radiation. Quantitative estimates were made associating the protective efficiency of the substances under study with variations in the electron parameters. PMID- 4023195 TI - [Radiosensitivity during the irradiation of animals in an altered gaseous environment. A comparative study on mice and rats of the radiation-protective effect of oxygen-deficient gas mixtures]. AB - The radioprotective effect of gas hypoxic mixtures containing 5, 7, 8, 10 and 15% of oxygen on mice and rats was comparatively studied. The dependence of DMF upon oxygen concentration in the mixture was approximated by a hyperbolic function similar to the dependence of the radiomodifying effect of circulatory hypoxia caused by radioprotective agents of the indolylalkylamine series. PMID- 4023197 TI - [Use of computed tomography in the diagnosis of uterine carcinoma recurrence- comparison with other imaging technics]. PMID- 4023198 TI - [Endomyelography and CT in hydrosyringomyelia and intramedullary drainage operations]. PMID- 4023199 TI - [Computed tomography following orbital surgery]. PMID- 4023200 TI - [Technic of injecting a contrast medium bolus for serial computed tomography]. PMID- 4023201 TI - [Guidelines for cerebral (brachiocephalic) angiography]. PMID- 4023202 TI - [Comparison of film roentgenography and electroroentgenography in the study of soft tissue tumors]. PMID- 4023203 TI - [Changes in bone structure with restricted mobility]. PMID- 4023204 TI - [Mineral metabolism in fractures based on results of photon absorptiometry]. PMID- 4023205 TI - [Comparative evaluation of data processing methods for ventilation and perfusion scintigraphy of the lungs]. PMID- 4023206 TI - [Significance of roentgenologic and nuclear medical studies for detecting urinary system disorders in lymphogranulomatosis]. PMID- 4023207 TI - [Film-screen combinations for x-ray diagnosis--present and future applications]. PMID- 4023208 TI - [Somatic irradiation risk tp patients during angiography]. PMID- 4023209 TI - [Initial experiences with a new stereo roentgen technic in general radiology]. AB - A new stereo X-ray technic, which is simple, easy to handle, universally applicable and without intrinsic disadvantages for the patient, is demonstrated. The two attributes of stereo X-ray, exact spatial representation of the relationship between structures and the addition of the two stereo pictures to give better signal/noise ratio are explained. The efficiency of this method is presented with investigations of the G.I. tract, abdominal angiography and the knee arthrography. PMID- 4023210 TI - [Traumatic vascular lesions. Radiological diagnosis--therapeutic consequences]. AB - Based on experience with 166 traumatic vascular lesions in 148 patients, the authors present the diagnostic methods and therapeutic consequences, which are at the moment applied at the Medical Highschool Hannover. PMID- 4023211 TI - [Intracranial forms of malignant lymphoma manifestations]. AB - Approximately 10% of patients with malignant lymphoma will show neurological symptoms at some time during the course of their illness. In non-Hodgkin lymphoma, CNS involvement is more frequent than in Hodgkin's disease. Diffuse histiocytic and poorly differentiated lymphomas, bone marrow involvement, advanced tumor stage and hematogenous spread are particular risk factors. Invasion of the spinal canal is the most common type of CNS involvement. Intracranial lesions, which are comparatively rare, may present as intracerebral metastases, epi- or subdural masses or focal or diffuse leptomeningeal disease. Lymphomatous leptomeningitis usually cannot be demonstrated by CT. On the other hand, dural and cerebral parenchymal lesions are sometimes highly characteristic of lymphoma as a result of their features and location. PMID- 4023212 TI - [Calcifications in a scar keloid]. AB - Ossification as a dystrophic alteration of scar tissue is not an unusual radiologic finding in patients who have had a laparotomy. Calcification or ossification in other than abdominal scars following injury, however, represent an extremely rare entity. A case of calcifications in posttraumatic keloid forming in the submandibular soft tissue is presented and the pathogenesis is discussed. PMID- 4023213 TI - [Bases for cost calculations in x-ray facilities]. AB - Economic implications of running an X-ray department in Switzerland will be illustrated by comparing operating costs of private radiological institutes with and without CT to the operating costs of large radiological departments in hospitals with and without CT and to the operating costs of simple X-ray equipment in general practitioners' offices. These cost calculations form the basis for cost-benefit analyses. PMID- 4023214 TI - Pulmonary nodules: detection of calcification by linear and pluridirectional movement in tomographic study. AB - Calcification within solitary pulmonary nodules (1-2 cm range) was demonstrated by conventional tomography in a group of 20 patients. Each patient had a combined tomographic examination consisting of 15 degrees linear movement followed by 34 degrees hypocycloidal movement. Linear tomography was superior to pluridirectional tomography in 19 cases for visualization of calcium within the nodule. The results are attributed to differences in contrast sensitivity and "blur" phenomena between the two tomographic movements. This study, although comparing a specific linear movement with a specific pluridirectional movement, provides insight into the differences between tomographic techniques for a given task. PMID- 4023215 TI - Tumor involvement of peripheral joints other than the knee: arthrographic evaluation. AB - Arthrography was performed in 24 patients with tumors in the region of the shoulder, elbow, wrist, hip, and ankle. Conventional arthrograms were supplemented by arthrotomograms and/or computed arthrotomograms as necessary. The presence or absence of joint involvement by tumor was correctly identified in 22 of 24 patients (91.7%). It is concluded that arthrography is a reliable method for detecting joint involvement by tumor, and should be performed if plain radiography, conventional tomography, and computed tomography are not definitive in demonstrating joint involvement. PMID- 4023216 TI - Venous "lakes" of the hands. AB - Following pharmacologic vasodilatation, multiple vascular "lakes" were observed on angiograms of the hand in 55 patients. Most had no history of vascular anomalies or disease. The authors believe that these lakes are venous structures and that their filling is a physiologic phenomenon. PMID- 4023217 TI - Breast cancer screening: the underuse of mammography. AB - The early detection of breast cancer is promoted by the American Cancer Society (ACS) and the American College of Radiology (ACR) by encouraging the regular use of three types of screening: breast self-examination (BSE), the clinical breast examination, and mammography. In August 1983, the ACS publicized seven recommendations pertaining to screening, including a revised statement about the routine use of mammography for women between the ages of 40 and 49 years. In response to the ACS statement, the present study assessed compliance with the updated recommendations for all three types of screening. The results show reasonable rates of compliance for the BSE (53%-69%) and clinical examination (70%-78%). In contrast, only 19% of the women between the ages of 35 and 49 and 25% of the women older than 50 reported complying with the recommendation to undergo one baseline screening mammogram. In addition, only 9% of the mammograms were obtained for the early detection of disease, which is the rationale for the recommendation. In fact, it appears that mammography is being performed mainly for the diagnosis of symptomatic women instead of the screening of asymptomatic women. Some implications for health education by physicians and the professional education by physicians and the professional education of physicians in the use of mammography are discussed. PMID- 4023218 TI - Greenfield caval filters: long-term radiographic follow-up study. AB - Sixty-nine patients with a Greenfield inferior vena cava (IVC) filter in place for 1-9 years were evaluated with supine abdominal radiographs. In 22 patients (32%) the filter span diameter had increased by 3-11 mm, and in six patients (9%) it had decreased by 3-18 mm. Twenty patients (29%) had caudad migration of 3-18 mm, and four (6%) had cephalad migration. In five patients (7%) the filter was at an angle of more than 16 degrees from the vertical. A decrease in filter span of 7 mm or more may result in IVC occlusion, whereas an increase of 6 mm or more may result in caval wall penetration. Caudad migration may be caused by a fibrous reaction around the struts which slowly draws the filter caudally. A change in filter angle may result from displacement of a strut into the right renal vein as well as from physiologic changes. The abdominal radiograph is a valuable method for follow-up study of patients with Greenfield filters if the filter position, span, migration, and angle are noted in the report. PMID- 4023219 TI - Nonoperative management of benign postoperative biliary strictures. AB - Selected benign biliary strictures can be treated safely and successfully by percutaneous balloon dilatation. Primary biliary strictures appear to be less responsive to balloon dilatation alone and require stenting with large catheters (16-20 F) for several months to permit scarring around the catheter. A long period of healing around such a large-bore stent is crucial to the success of such treatment. The most important physiologic indicators for successful dilatation are a long period of stricture challenge with a catheter placed proximal to the dilated segment to allow bile to drain internally across the previously strictured segment, and a near anatomic result as demonstrated by cholangiogram. PMID- 4023220 TI - Intrahepatic amebic abscesses: indications for and results of percutaneous catheter drainage. AB - Medical therapy is standard for intrahepatic amebic abscess and generally is effective. However, we have encountered a group of patients in whom percutaneous aspiration and drainage was indicated due to uncertainty of diagnosis or clinical deterioration of the patient. Twenty such patients underwent percutaneous drainage with ultrasound or CT guidance, and each patient was cured (appropriate antibiotics were administered concomitantly). The specific indications for intervention were to differentiate pyogenic from amebic abscess, pain and imminent rupture, poor response to medical therapy, false-negative results of serologic tests, noncompliance with medical treatment, left lobe abscess, and pregnancy. Diagnosis of amebiasis from examination of the fluid was seldom possible, while findings from core biopsy of the wall of the abscess led to diagnosis in three cases. Recurrence necessitating redrainage occurred in three patients; in each, catheters were removed the same day drainage was performed. There were three minor complications. Differences from percutaneous management of pyogenic abscesses included more rapid removal of catheters (four days), more frequent use of US guidance, and more common use of the prone angled approach to avoid pleural contamination. Catheter drainage may be curative and may expedite care for problematic amebic liver abscesses in selected cases. PMID- 4023221 TI - Biliary stent endoprosthesis: analysis of complications in 113 patients. AB - Stent endoprosthesis has been advocated as an alternative to internal-external catheter drainage for decompression of biliary obstruction, but drawbacks have never been specifically analyzed, to our knowledge. A retrospective review of 118 biliary stent endoprostheses placed in 113 patients assessed the frequency, nature, and treatability of significant complications. Complications were categorized as early (morbidity or mortality within the first 30 days) or late (after 30 days). The early complication rate was 17% (19/113); the late complication rate, 31% (32/102). Early complications were most often due to unstable stent positioning in technically difficult procedures involving periportal obstruction (4/8), while the most common late problems were lumen occlusion (23/102 [23%]), migrations (6/102 [6%]), and tumor overgrowth of the stent (3/102 [3%]). Neither the histologic features nor the location of the primary tumor correlated with the potential for long-term stent dysfunction. Specific treatment of complications was carried out in 17 of 102 patients (17%) and almost invariably required readmission and remanipulation or de novo biliary drainage. PMID- 4023222 TI - Central nervous system anoxic-ischemic insult in children due to near-drowning. AB - An analysis of admission and follow-up CT examinations of the brains of 17 children who had nearly drowned (15 of whom were comatose and two of whom were conscious on admission) indicated that a normal initial CT scan is common in the majority of comatose patients, a severe neurologic outcome may develop in spite of a normal initial CT examination, and abnormal initial or follow-up CT findings indicate the strong but not inevitable probability of a severe neurologic outcome. We conclude that when there is no head trauma, an initial CT examination is not necessary. Prediction of the clinical outcome cannot be made on the basis of the initial CT findings. PMID- 4023223 TI - Central nervous system hypoxia in children due to near drowning. AB - Fourteen children who experienced acute, profound central nervous system hypoxia secondary to near drowning, aspiration, or respiratory arrest underwent CT examination. During the first week after the episode, the most frequent finding was a loss of gray-white matter differentiation. Other findings included effacement of sulci and cisterns, focal areas of edema in the cerebral cortex or basal ganglia, and hemorrhagic infarctions of the basal ganglia. Subsequent CT scans obtained from two weeks to five months after the hypoxic episode showed progression of cerebral loss from cortical infarction with gyral hemorrhage and enhancement to global parenchymal atrophy. The prognosis is poor in these patients: seven children experienced severe neurologic deficits and seven died. PMID- 4023224 TI - Nasopharyngeal carcinoma: clinical and radiographic findings in children. AB - Nasopharyngeal carcinoma (NPC) in childhood occurs so infrequently that it is not suspected in affected children until the disease has been present for a long time and local spreading has occurred. The survival rates are therefore quite poor. Six children with NPC are described. A massive local lymph node spread simulating lymphoma was present in half of the patients; in the other half the disease was more subtle, presenting with epistaxis and CNS involvement. If an evaluation of the nasopharynx were part of the initial physical examination in children, the diagnosis of NPC would be made earlier and survival rates would improve. PMID- 4023225 TI - Intermittent hydronephrosis: a unique feature of ureteropelvic junction obstruction caused by a crossing renal vessel. AB - Obstruction at the ureteropelvic junction (UPJ) is usually intrinsic. Recently, however, 13 (11%) of approximately 120 children with UPJ obstruction were found to have extrinsic obstruction caused by a lower-pole renal vessel. In each case, the obstruction was confirmed at the time of surgery. Most of these patients had intermittent pain. Excretory urograms did not show obstruction between episodes of pain, but when a urogram was obtained during an episode, marked obstruction was noted. Contrast agent trapped in a segment of proximal ureter suggests the presence of an extrinsic obstruction. Properly timed renal imaging, therefore, can identify the urinary tract as the source of the symptoms. PMID- 4023226 TI - Aluminum bone disease in children: radiographic features from diagnosis to resolution. AB - Two children with chronic renal failure developed aluminum intoxication as a result of long-term ingestion of aluminum hydroxide for the control of hyperphosphatemia. In each child, bone biopsy confirmed severe osteomalacia, the absence of features of hyperparathyroid bone disease, and massive aluminum deposition at the bone-osteoid junction. Radiographs during the period of aluminum intoxication demonstrated osteopenia, pathologic fractures, fraying of the metaphyses of the long bones, and widening of the physis. When aluminum hydroxide therapy was discontinued (each patient) and aluminum was removed with chelation therapy (one patient), radiographs demonstrated a distinctly unusual pattern of healing. Calcification of the long bones began at the most recently formed osteoid and then proceeded toward the diaphysis. This unusual healing pattern created lucent defects and a transient "bone within a bone" appearance, which resolved with further healing. PMID- 4023228 TI - Lumbar intervertebral disk: correlative MR and anatomic study. AB - Exactly corresponding magnetic resonance (MR) images and anatomic sections were obtained of cadaveric lumbar intervertebral disks. MR differentiated two major components of the intervertebral disk, one corresponding to the collagenous fibers in the periphery of the disk, the other corresponding to the combination of nucleus and annulus. The vertebral osseous end plate appears to be faintly resolved, but may be simulated by a chemical shift artifact. More correlative studies and development of additional techniques are needed to characterize completely the MR appearance of the intervertebral disks. PMID- 4023227 TI - Ocular and orbital lesions: surface coil MR imaging. AB - Nine lesions, four ocular (three melanomas, one hemangioma) and five orbital (two perioptic meningiomas, one hemangioma, one pseudotumor, one mucocele), were evaluated by magnetic resonance surface coil imaging at 1.5 T. Small ocular lesions with 3.9-4.5-mm-elevation were demonstrated. The use of two different pulse sequences resulted in separation of melanoma from adjacent retinal detachment. Contrast obtained between orbital lesions and the adjacent normal structures was better than that demonstrated with high-resolution computed tomography. PMID- 4023229 TI - Use of CT in the evaluation of cochlear otosclerosis. AB - Otosclerosis (otospongiosis) occurs when the hard endochondral bone of the otic capsule is replaced by spongy vascular foci of haversian bone. Using computed tomography (CT), we studied the ears of 32 selected patients with mixed or sensorineural hearing loss (one patient had normal hearing); 24 were suspected of having otosclerosis. CT proved valuable in detecting cochlear otosclerosis, foci of demineralization, and changes in bony texture and enables the easy recognition of subtle radiographic findings. Our paper also reports the CT findings of temporal bones in osteogenesis imperfecta and Paget disease. PMID- 4023230 TI - Use of CT in stapedial otosclerosis. AB - Otosclerosis (otospongiosis) is a primary focal disease of the labyrinthine capsule. The stapes footplate is fixed when the spongiotic focus expands and invades the oval window. Persons with stapedial otosclerosis experience a progressive conductive hearing loss. In many cases, cochlear degeneration is observed, in which a mixed hearing loss occurs. Using computed tomography (CT), we studied the ears of 45 selected patients with conductive or mixed hearing loss. CT proved valuable in determining otosclerotic changes of the oval window and otic capsule. Spongiotic changes of the otic capsule are better appreciated by CT than complex motion tomography. The usefulness of CT in diagnosing other causes of conductive or mixed hearing loss is also described. PMID- 4023231 TI - Aspergillosis of the paranasal sinuses. AB - The authors examined 105 proved cases of aspergillosis involving the paranasal sinuses or nasal fossa. Mycosis was always unilateral, and the maxillary sinus was infected in all cases. Early stages were manifested by an intraluminal soft tissue mass representing the mass of mycelia. Fifty-nine patients (56%) demonstrated very dense intraluminal calcifications. Such dense concretions suggest the diagnosis of aspergillosis. PMID- 4023232 TI - Left ventricular volumes measured by MR imaging. AB - We assessed the potential of proton magnetic resonance (MR) imaging for accurately measuring left ventricular volumes using 15 latex casts of excised human left ventricles. The casts were submerged in water to stimulate the endocardial left ventricular cavity interface in in vivo imaging conditions. Tomographic image sections perpendicular to the long axis of the cast were obtained, spanning each cast from apex to base. Simpson's rule was used to calculate the cast volumes. Correlation between the actual cast volumes (as measured by the displacement method) and the calculated volumes using MR imaging for the 15 casts was excellent. Our data demonstrate that MR imaging accurately measures cardiac chamber volumes in this in vitro model. PMID- 4023233 TI - Radiation fibrosis: differentiation from recurrent tumor by MR imaging. AB - Magnetic resonance (MR) images of 21 patients who had undergone radiation therapy were analyzed and compared with those of 15 patients who had untreated tumors. T2 weighted images (TR = 1,500 msec, TE = 90 msec) were most helpful in distinguishing recurrent tumor from radiation fibrosis. Radiation fibrosis, like muscle, usually remained low in signal intensity on T2-weighted images, while tumor demonstrated higher signal intensity. In no patient was the signal intensity of tumor the same or less than muscle on the T2-weighted images. However, relatively high signal intensity on T2-weighted images is not specific for tumor recurrence and may be seen in acute radiation pneumonitis, infection, hemorrhage, and even pulmonary radiation fibrosis. PMID- 4023234 TI - Esophageal imaging by MR and CT: study of normal anatomy and neoplasms. AB - In 20 patients with normal esophagi, spin-echo magnetic resonance (MR) imaging was performed to determine the appearance at different pulse sequences and T1 and T2 values. Twelve patients with esophageal carcinoma were also studied by both MR and computed tomography (CT); in ten, there was correlation with surgical and pathologic findings. Both MR and CT showed low accuracy in staging the tumors (40% and 70%, respectively), mainly because of difficulty in detecting tumor invasion through the muscle layer into periesophageal fat. Relatively T1-weighted images (repetition time, 0.5 second; echo time, 28 msec) were best for depiction of both normal esophageal anatomy and esophageal tumors. T1 and T2 measurements varied widely for both normal and abnormal esophagi and thus were not useful in predicting histologic findings. PMID- 4023235 TI - Peripheral vascular disease: correlation of MR imaging and angiography. AB - The capability of magnetic resonance (MR) imaging for detecting aortic, iliac, and femoral stenoses and occlusions was evaluated. Multisection spin-echo studies at 0.35 tesla were obtained of the infrarenal aorta to the femoral bifurcation in 24 patients, all of whom had undergone intraarterial angiography within 14 days of imaging. Transaxial MR images were compared with the angiograms. Arterial stenoses and occlusions in these vessels detected by MR imaging correlated with angiographic findings in 91% of the instances. Protrusional atherosclerotic plaques and occlusions and stenoses in the aortoiliac region were demonstrated accurately on MR images; complications of previous vascular surgery, such as aneurysms at sites of previous anastomoses or endarterectomy, were also identified. Due to the limited spatial resolution, MR images failed to demonstrate some femoral stenoses. MR imaging may be used for evaluation of aortoiliac vascular disease and for follow-up study after surgical revascularization. However, the limited spatial resolution, noncomposite display of the aortoiliofemoral circulation, and lack of evaluation of peripheral runoff provided by current MR imaging techniques militate against its replacing angiography prior to vascular intervention. PMID- 4023236 TI - Inner volume MR imaging: technical concepts and their application. AB - Although cross-sectional magnetic resonance examination of the head and body is useful for screening large regions of tissue, subsectional regions of the head and body often need to be examined. Orthogonally directed, selectively irradiated planes with different flip angles produce a spatially limited signal region from which two- or three-dimensional volume images can be reconstructed. Images with limited fields-of-view can be acquired in reduced imaging time. We present a general description of this technique. These subsectional or "inner volume" images eliminate respiratory motion artifacts by excluding moving tissues from the imaged volume. A result of this technique is a high signal from rapid pulsatile blood flow, produced without cardiac gating the pulse sequence. PMID- 4023237 TI - MR imaging technology: maximizing the signal-to-noise ratio from a single tissue. AB - The pulse-sequence equations for spin-echo magnetic resonance imaging were used to determine interpulse delay times that give the highest signal-to-noise ratio from a single tissue. This theoretical result was then verified experimentally using 1-, 2-, and 5-mM/l copper sulfate solutions imaged on a 0.15-T resistive system. Theoretical analysis determined the spin-echo interpulse delay times that maximize the signal-to-noise ratio from a single tissue as TEopt = TEmin, the minimum echo delay time permitted by the system, and, to a good approximation, TRopt = 1.27 T1 + 1.90 TEmin, with T1 the longitudinal magnetic relaxation time of the tissue. Phantom measurements of the signal-to-noise ratio in a typical imaging system confirmed the theoretically determined TRopt values to within 7%. PMID- 4023238 TI - Constrictive pericardial disease: prognostic significance of a nonvisualized left ventricular wall. AB - Twenty-six patients with pericardial constriction confirmed by catheterization were studied by dynamic computed tomography (CT). The posterolateral wall of the left ventricular myocardium was not detected in five patients (19.2%). None had evidence of previous myocardial infarction on electrocardiogram or levocardiogram. In 16 patients, a pericardiectomy was performed to remove pericardial constriction. All five patients with nondetectable posterolateral walls of the left ventricle died at or immediately following surgery because of acute myocardial failure. Nonvisualization of the posterolateral wall of the left ventricle in patients with constrictive pericarditis suggests the presence of myocardial fibrosis or atrophy. Surgery is an extremely high risk in these patients. PMID- 4023239 TI - False lumens in type III aortic dissections: progress CT study. AB - The fate of false lumens in 13 patients having Type III aortic dissections was studied using computed tomography (CT). Contrast media filled false lumens with or without thrombosis were observed in ten patients; the false lumens of three patients were entirely thrombosed at initial examination. Follow-up CT studies showed shrinkage or disappearance of the false lumens with thrombosis in four patients, progression of thrombosis in two patients, and enlargement of the false lumen in one patient who subsequently required surgical repair. No change was observed in the remaining six patients during our observation period. CT study provides useful information for evaluating the efficacy of medical treatment and the timing of surgical intervention during follow-up evaluation of medically treated Type III aortic dissections. PMID- 4023240 TI - Paratracheal lymphadenopathy: radiographic findings and correlation with CT. AB - Possible signs of paratracheal lymphadenopathy on the posteroanterior (PA) chest radiograph were assessed in 98 patients and correlated with computed tomography (CT). The nodes were normal in size in 62 patients and enlarged (greater than 15 mm) in 36. Among the latter group, widening of the right paratracheal stripe was seen in 11 (31%) and enlargement of the azygos node in 15 (42%). While the lateral contour of the superior vena cava (SVC) was convex in 46 patients (47%), 81 (83%) had an increased density in the region of the SVC. When all four parameters were combined, lymphadenopathy could be detected on the PA view in 87 patients (89%). CT demonstrated that the enlarged nodes were anterolateral rather than directly lateral to the trachea and also immediately posterior to the SVC, explaining the findings on the PA radiograph. PMID- 4023241 TI - Acute pancreatitis: prognostic value of CT. AB - In 83 patients with acute pancreatitis, the initial computed tomographic (CT) examinations were classified by degree of disease severity (grades A-E) and were correlated with the clinical follow-up, objective prognostic signs, and complications and death. The length of hospitalization correlated well with the severity of the initial CT findings. Abscesses occurred in 21.6% of the entire group, compared with 60.0% of grade E patients. Pleural effusions were also more common in grade E patients. Grades A and B patients did not have abscesses, and none died, regardless of the number of prognostic signs. Abscesses were seen in 80.0% of patients with six to eight prognostic signs, compared with 12.5% of those with zero to two. The use of prognostic signs with initial CT findings results in improved prognostic accuracy. Early CT examination of patients with acute pancreatitis is a useful prognostic indicator of morbidity and mortality. PMID- 4023242 TI - Hydranencephaly: US appearance during in utero evolution. AB - Massive intracranial hemorrhage was diagnosed in utero in a 27-week-old fetus. The subsequent development of hydranencephaly was monitored by ultrasound until term. PMID- 4023243 TI - Pectus excavatum in children: pulmonary scintigraphy before and after corrective surgery. AB - Regional distribution of pulmonary function was evaluated preoperatively and postoperatively with xenon-133 perfusion and ventilation scintigraphy in 17 patients with pectus excavatum. Ventilatory preoperative studies were abnormal in 12 of 17 patients, resolving in seven of 12 postoperatively. Perfusion scans were abnormal in ten of 17 patients preoperatively; six of ten showed improvement postoperatively. Ventilation-perfusion ratios were abnormal in ten of 17 patients, normalizing postoperatively in six of ten. Symmetry of ventilation perfusion ratio images improved in six out of nine in the latter group. The distribution of regional lung function in pectus excavatum can be evaluated preoperatively to support indications for surgery. Postoperative improvement can be documented by physiological changes produced by the surgical correction. PMID- 4023244 TI - Postcholecystectomy syndrome: evaluation using biliary scintigraphy and endoscopic retrograde cholangiopancreatography. AB - We prospectively studied 30 patients with postcholecystectomy syndrome to determine the efficacy of biliary scintigraphy in the detection of stenosis of the sphincter of Oddi. All patients underwent endoscopic retrograde cholangiopancreatography (ERCP). Biliary scintigraphy disclosed stenosis of the sphincter by agreement with the ERCP or surgical findings in nine (90%) of ten patients and in eight (100%) of eight patients with biliary obstruction from other causes. Retention of activity at 2 hours in visually prominent ducts was the best predictor of abnormal biliary drainage. Biliary scintigraphy is a useful, noninvasive screening test for the detection of postcholecystectomy biliary obstruction. PMID- 4023245 TI - Sphincter of Oddi stenosis: diagnosis using hepatobiliary scintigraphy and endoscopic manometry. AB - To determine the role of radionuclide imaging in diagnosing sphincter of Oddi stenosis, 21 patients with symptoms suggesting this disorder underwent endoscopic retrograde cholangiopancreatography, cholescintigraphy, and, when possible, endoscopic manometry. Those patients with abnormal hepatobiliary scintigraphy results--based on our criteria of delayed biliary intestinal transit, abnormal duct size, and abnormal time-activity dynamics and obstruction--had a mean basal sphincter pressure of 38.5 mm Hg. Sphincter pressures could not be measured in six patients with sphincters too tight to cannulate. Ten patients who underwent hepatobiliary scanning both before and after sphincter surgery had normal scan results on the repeat study. Hepatobiliary imaging appears useful for diagnosis of sphincter of Oddi stenosis in selected patients in whom manometry cannot be performed and for objective assessment of response to therapy. PMID- 4023246 TI - Pericholecystic hepatic activity in cholescintigraphy. AB - Gallbladder nonvisualization in cholescintigraphy has been shown to be a reliable finding in acute cholecystitis. In some cholescintigrams, we have observed faintly increased pericholecystic hepatic activity in conjunction with gallbladder nonvisualization. To determine the frequency and significance of the pericholecystic hepatic activity finding, we evaluated 334 consecutive adult patients who had cholescintigrams with technetium-99m diisopropylphenylcarboamoyl iminodiacetic acid. Pericholecystic hepatic activity was seen in 21% of the abnormal scans demonstrating gallbladder nonvisualization but in none of the other scans. Thirteen of these patients underwent surgery; 11 (85%) were found to have acute cholecystitis, and two (15%) had chronic cholecystitis. Four patients (31%) had acute gangrenous cholecystitis, and five (39%) had cholecystitis complicated by gallbladder perforation. The pericholecystic hepatic activity sign is not specific for gangrenous cholecystitis or gallbladder perforation but does reliably indicate inflammatory gallbladder disease and is associated with a relatively high incidence of cholecystitis complicated by perforation. PMID- 4023247 TI - Malignant melanoma of the eye: treatment of posterior uveal lesions by Co-60 plaque radiotherapy versus enucleation. AB - Survival rates and visual acuity of 100 patients treated for posterior uveal malignant melanoma by cobalt-60 plaque radiotherapy were compared with 150 patients treated by enucleation for the same disease. Life-table comparisons of the entire group showed significant differences in survival rates, with plaque radiotherapy patients appearing to fare better. However, when patients with small or medium tumors were compared, only slight differences were seen, implying that criteria used to select patients for treatment may affect interpretation. The two groups were also compared using the Cox proportional hazards model, which predicts survival based on the impact of clinical variables. In this analysis, the survival rates of the plaque radiotherapy group were no worse than those of the enucleation group. The advantage of conservative therapy lies in the potential to preserve useful vision over a considerable time. Because patients were specifically selected for treatment modality and because the study size used to calibrate the Cox model was small, the results of this study must be interpreted with caution. PMID- 4023248 TI - Statement from the 1985 Paris meeting of the International Commission on Radiological Protection. Special report. PMID- 4023249 TI - A rectal monitor for use with afterloading intracavitary radioactive implants. AB - A battery-powered monitor that uses a miniature Geiger-Muller tube operating in the pulse-counting mode has been constructed. It is used with low-activity cesium 137 sources. The monitor gives a reading within about 1 second, has a standard deviation of 2% of the mean, and is safe, reliable, and stable. PMID- 4023250 TI - Orbital tumor irradiation using non-coplanar beams. AB - Irradiation of the orbit is often associated with substantial dose inhomogeneity resulting from the insertion of lens blocks. We postulated that such dose inhomogeneity, which often exceeds 40%, could be halved by the use of two pairs of wedged beams, one angled in the sagittal plane and the other in the commonly employed transverse plane. The sagittal plane is obtained by turning the treatment couch 90 degrees. All beams carried a central-axis lens block and were angled 30 degrees relative to the vertical. Verification of dose distribution was obtained by film dosimetry in a head phantom for central- and off-axis planes. These measurements indicate that significant improvement in dose homogeneity over alternate methods can be achieved with this technique. PMID- 4023251 TI - Temporomandibular joint arthrography of normal subjects: prevalence of pain with ionic versus nonionic contrast agents. AB - Bilateral temporomandibular joint (TMI) arthrography was performed in 31 healthy subjects to determine the prevalence and degree of postprocedural pain and to establish if morbidity could be decreased by use of a nonionic contrast agent. Ionic contrast material (Hypaque 60%) was injected on one side and nonionic contrast material (Amipaque) on the other side. The pain experienced in the 5 days following arthrography was graded and recorded. Discomfort, when present, was described as mild or moderate and usually lasted for 2 days after the procedure. In no instance was the pain considered severe. There was significantly less pain on the side that was injected with nonionic contrast material. The invasiveness of the examination should not be a deterrent since discomfort from TMJ arthrography is minimal when performed by an experienced arthrographer; use of a nonionic contrast agent can further decrease the pain. PMID- 4023252 TI - Antegrade internal ureteral stenting: a technical refinement. AB - A pliable, easy to place, double pigtail, internal ureteral stent made of elastomeric polyurethane is described. The tapered distal pigtail end minimizes bladder irritation and the combination of a pusher and absorbable suture enables optimal placement of the proximal pigtail end in the renal pelvis. Ten stents used in eight patients remained functional without bladder irritation for a mean period of 8 months (range, 2-14 months). PMID- 4023253 TI - Surgical ligation clip artifacts on CT scans. AB - Surgical ligation clips of various materials were scanned in a water-filled phantom to determine what artifacts would be produced. Tantalum clips produced severe image degradation, while stainless steel clips produced less severe degradation. Minimal artifacts were observed with titanium clips. Clips molded from an absorbable polymeric material, polydioxanone, were visible on computed tomography (CT) scans and had the least effect on the CT image. PMID- 4023254 TI - Leg-length determination with biplanar CT scanograms. AB - Computed tomography (CT) scanograms provide an accurate method for evaluation of leg-length discrepancy. Flexion of a leg may be missed on a single frontal projection, and the measurements obtained will be erroneously shortened. When performing CT sonography, lateral views of the limbs may be easily and rapidly obtained without having to change the position of the patient. This permits assessment of limb flexion. PMID- 4023255 TI - Supine thallium 201 cardiac testing compared with treadmill testing. AB - Although thallium 201 stress testing is usually performed on a treadmill (Tl-TM), supine bicycle-ergometer-exercise thallium 201 testing (Tl-SB) has been reported. We performed a study to evaluate the accuracy of Tl-SB in evaluation of coronary artery disease and to correlate its results with those of Tl-TM. Fifty patients underwent both Tl-SB and Tl-TM testing in random sequence an average of 1 week apart. Tl-TM produced significantly higher maximal pulse rates and pulse-pressure products. Cardiac thallium kinetics differed significantly between Tl-SB and Tl TM with Tl-TM producing greater initial myocardial uptake and greater thallium 201 washout between immediate and delayed images. Compared with results of catheterization, Tl-TM was significantly more accurate than Tl-SB for evaluation of coronary artery disease, with higher sensitivity and specificity. PMID- 4023256 TI - Very stiff guide wire with a floppy tip. AB - Many interventional procedures, particularly dilation of tracts, require stiff guide wires with a floppy tip. Such a guide wire was specially constructed and is commercially available. PMID- 4023257 TI - Re: Reticular pattern as a radiologic sign of the Barrett esophagus. PMID- 4023258 TI - Re: Candida esophagitis: accuracy of radiographic diagnosis. PMID- 4023259 TI - Re: A simple method for retrieving metal foreign objects from an MR imager. PMID- 4023261 TI - Third International Duran-Reynals Symposium: Viruses, Oncogenes, and Cancer. Barcelona, Spain, May 14-17, 1984. PMID- 4023260 TI - Re: Immediate barium enema following colorectal biopsy. PMID- 4023262 TI - Cooperation between cellular oncogenes in the transformation of primary rat embryo fibroblasts. PMID- 4023264 TI - Exploring carcinogenesis with retroviral and cellular oncogenes. PMID- 4023263 TI - Genetic factors in susceptibility to viral leukemogenesis. PMID- 4023266 TI - [N-acetylgalactosamine 4-sulfatase and 6-sulfatase]. PMID- 4023265 TI - Activation of c-ras oncogenes is associated with tumor induction in experimental animals. PMID- 4023267 TI - [Freud's psychological methods in art]. PMID- 4023268 TI - ["Always daughter of the air." The dangerous life of Effie Briest]. PMID- 4023269 TI - [Frank Wedekind's street ballad "The teacher of Mezzodur." A poetisized case study from the area of forensic psychiatry]. PMID- 4023270 TI - [The ruined picture of modern man in Gunter Grass' novel "The Tin Drum"]. PMID- 4023271 TI - Age and functions of the transient component of ON and OFF responses in visual processes. PMID- 4023272 TI - Visual-field differences for a number--non-number classification of alphabetic and ideographic stimuli. PMID- 4023273 TI - A study of braille reading: 1. Reading speed as a function of hand usage and context. PMID- 4023274 TI - A study of braille reading: 2. Patterns of hand activity in one-handed and two handed reading. PMID- 4023275 TI - Movement cues and body orientation in recall of locations by blind and sighted children. PMID- 4023276 TI - [Precision measurements of the Doppler broadening of positron annihilation radiations using a simultaneous and comparative detection technique]. AB - The precision measurement system of the Doppler broadening profiles of positron annihilation radiations using a simultaneous and comparative detection technique has been developed and was applied to the study of grown-in defects in indium phosphide (InP). Annihilation energy spectra in the specimen to be examined and in a standard one were simultaneously measured by a single pure Ge detector. Each specimen incorporated a 22Na positron source in a sandwiched form between two identical samples. The colinear directional correlation of two photon annihilation allows us to route the output of ADC (analogue to digital converter) to different memory sections. For the purpose of discrimination which source emitted the analysed gamma ray, two auxiliary NaI(Tl) detectors were used. Such a simultaneous and comparative measurement was found to be free of drift in electronics during the course of experiments over 10 weeks. Furthermore, the coincidence measurement reduced the background due to 1.28 MeV prompt gamma rays. This technique was applied to the detection of a positional distribution of grown in defects in an InP wafer, which was slivered along a plane involving growth axis from the single crystal ingot grown by a liquid encapsulated Czochralski technique. The narrowing of Doppler broadening profiles was observed at the center and at the periphery of the wafer. This result well resembles the positional distribution of dislocations observed by the etch pit counting. PMID- 4023277 TI - Substoichiometric determination of cobalt in crud. AB - A substoichiometric extraction method with nitroso-R salt (NRS) has been studied for the determination of trace Co in crud. The Co-NRS complex is extracted substoichiometrically into Capriquat-CHCl3 at pH 6.5-9.0 in 20 min of shaking time. The analytical results obtained by the method are within 3% of relative error in the determination range of 5 to 50 micrograms. The proposed method is simple and has sensitivity of 0.5 micrograms, though Fe(II), Ni(II) and Cu(II) seriously interfere. The results applied for the determination of trace Co in crud are described. PMID- 4023278 TI - [Separation of HT and HTO in the atmosphere with porous Vycor glass tube]. AB - The continuous selective monitoring of tritium gas (HT) in the air containing HT and tritiated water vapor (HTO) was investigated by using the separation cell made of porous Vycor glass tube. On admitting the air containing HT or HTO into the separation cell, HT permeated immediately through the Vycor tube depending on the partial pressure, however, HTO permeated very slowly through the Vycor tube after initial induction period. The initial induction period was elongated with a rise of the temperature of separation cell and then the permeability of HTO decreased remarkably. In the air containing HT and water vapor, the permeation of HT through the Vycor tube was considerably restricted by the water vapor adsorbed on the Vycor tube at lower temperature (at 25 degrees C) but it was hardly affected by water vapor at higher temperature (greater than 50 degrees C) since water vapor was difficult to adsorb on the Vycor tube. These results indicated that HT in the air containing HT and water vapor can be continuously monitored by using the separation cell made of the porous Vycor glass tube. PMID- 4023279 TI - [Safety mechanism against earthquakes for gamma radiography apparatus]. PMID- 4023280 TI - [Scoring system for type B hepatitis associated antigen and antibody by a radioimmunoassay kit--anti HBc]. PMID- 4023281 TI - [Experimental and clinical studies on a TPA kit, Prolifigen]. PMID- 4023282 TI - [Surface treatment by a low energy electron beam. Present status and future prospect]. PMID- 4023283 TI - [Tests on type A packages for radioisotope transportation]. PMID- 4023285 TI - Identification of genotoxic and epigenetic carcinogens in liver culture systems. AB - Liver culture systems are available for identifying the DNA reactivity of carcinogens and a cell membrane effect, which appears to be associated with neoplasm-promoting ability. Using these and other approaches, carcinogens can be categorized as genotoxic or epigenetic. This distinction has implications for risk assessment. PMID- 4023284 TI - Toxicity, biodegradability, and accumulation of a number of Cl/N-containing compounds for classification and establishing water quality criteria. AB - The evaluation of the ecotoxicity of chemical compounds is often hampered by the scarcity of the literature data on toxicity, biodegradability, and accumulation. In this study additional data on 16 Cl/N-containing organic compounds were gathered by laboratory experiments. For assignment to so-called gray or black lists, two different classification schemes were used. According to both schemes 3-nitrotoluene, 1,2- and 1,3-dichlorobenzene, the 1-chloro-nitrobenzenes, 2,3 dichloronitrobenzene, 2-chloroaniline, and 2-chloro-4-nitroaniline were marked as black list substances, primarily based on poor biodegradability; 2- and 4 nitrotoluene, nitrobenzene, and 2-methoxyaniline were classified as gray list substances. For 3- and 4-methoxyaniline and 1,4-dichlorobenzene no agreement in classification was obtained. Additionally, water quality criteria are proposed for 2-, 3-, and 4-nitrotoluene and nitrobenzene, based on long-term toxicity data: respectively 0.3, 0.2, 0.4, and 1.0 mg/liter. PMID- 4023286 TI - Legal and political aspects of the regulation of chemicals: Swiss environmental protection law. AB - The premises for regulations in the field of ecology demonstrate clear scientific deficiency regarding basic relations in technical and scientific aspects but also a deep political disagreement on how to cope with them. These characteristics result in a new kind of law whose prime notion is to satisfy a social concern. The Swiss ecology regulation may be qualified as a so-called "tentative legislation." The structure of this kind of legislation is shown in the use of unclear notions, goal-oriented rules, and deviation to governmental and administrative regulation and may even lead to a more or less symbolic use of legislation. PMID- 4023287 TI - Some issues in the quantitative modeling portion of cancer risk assessment. AB - Several questions should be asked in order to determine the relevance and scientific merit of a quantitative cancer risk assessment. Twenty such questions are formulated here and briefly discussed. These questions are intended to identify important issues and serve as a checklist for risk managers and developers of quantitative risk assessments. Among the many factors involved in these questions are the carcinogenic response, quantal response models, time to response, competing risks, model shapes, goodness of fit, dose scale, high-to-low dose extrapolation, consistency across different subjects, animal-to-human extrapolation, route-to-route extrapolation, exposure durations and patterns, short-term tests, consistency with human epidemiological data, human exposures, statistical variability, impacts of assumptions and policy decisions and value judgments, risk characterization, upper and lower bounds, and keeping pace with scientific advances. PMID- 4023288 TI - The role of the chimpanzee in the evaluation of the risk of foreign chemicals to man. AB - Various species of laboratory animals are used to evaluate the efficacy and safety of drugs in man. However, the extrapolation of data from animals to man is often complicated by species differences in the disposition of foreign chemicals. The findings of comparative metabolism studies are used to illustrate species differences in metabolic pathways, rates of biotransformation, kinetics, and excretion routes. Biochemical and structural consequences of the significant differences in enzyme induction between rodents and primate species are discussed. Among the primates, the chimpanzee has been shown to be the most closely related to man not only in the disposition of xenobiotics, but also in the aspects of endocrinology, serology, and immunology. It would, therefore, be the best possible model to predict the fate and effects of foreign chemicals in man. Due to the limited availability of chimpanzees, however, they can only be used for the evaluation of the most critical chemicals and drugs. Comparative metabolism and disposition studies, e.g., of compounds representative of classes of chemicals in chimpanzees and other animals. Only when the pertinent differences between the selected test species and man are known can correct extrapolations to man be made. PMID- 4023289 TI - Uncertainty factors and interindividual variation. AB - Human variation in response to environmental agents appears often greater than a factor of 10, sometimes even up to several orders of magnitude. However, the vast majority of people studied to date respond within a factor of 10. The implications of these findings for the current use of uncertainty factors in regulatory toxicology is discussed. PMID- 4023290 TI - Potential consequences of a fire in an insecticide storage facility. AB - Assumptions are identified and made in an attempt to model the acute human health risk associated with a hypothetical fire in an insecticide storage facility. The insecticides used in the model are endrin and dimethoate. The model indicates that persons residing a few hundred meters from the facility could suffer a variety of adverse effects, including possible death from contact with smoke from a prolonged, low-temperature fire. Knowledge of the special hazards of cool toxic smoke as well as current atmospheric conditions could be of use to fire fighters. That is, fire fighters might wisely choose to promote a fast, hot fire which would propel toxicants high into the atmosphere rather than risk local fumigation. PMID- 4023291 TI - Histologic and cytogenetic effects of redentin on the spermiogenesis and bone marrow cells of the mouse, an in vivo experiment. AB - The chromosomes in bone marrow cells and spermatocytes of Redentin (1 X 20 mg/kg, po)-treated CFLP strain male mice were examined. Spermiogenesis was checked histologically. On the basis of the results, it can be stated that Redentin, at this experimental dosage, did not induce chromosome aberrations nor did it damage spermiogenesis. PMID- 4023292 TI - A testing strategy to evaluate the mutagenic activity of industrial chemicals in cultured mammalian cells. AB - Based on the published guidelines of regulatory agencies and the latest scientific findings, an experimental strategy for the routine testing of the mutagenic activity of industrial chemicals in mammalian cells in vitro is designed. The strategy includes three individual experiments: (1) a range-finding experiment for cytotoxicity to determine the appropriate doses to be used in subsequent mutagenicity testing; (2) mutagenicity testing at limited doses with different concentrations of Aroclor 1254-induced rat liver homogenate (S9); and (3) a more extensive dose-response experiment using an S9 concentration determined to be optimum in mutagenicity. Besides satisfying the guidelines of regulatory agencies, this strategy should yield data that allow sound scientific judgment on the mutagenicity of the chemicals tested. PMID- 4023293 TI - The use of epidemiology, scientific data, and regulatory authority to determine risk factors in cancers of some organs of the digestive system. 1. Introduction. AB - Continuing concern about cancer provides an impetus for continuing efforts to reduce its incidence and improve its treatment. Efforts to improve treatment are seen as highly desirable and excite little controversy, but attempts to reduce cancer incidence by regulatory intervention raise questions about cost-benefit ratios. Difficulties of making cost-benefit decisions are compounded by the lack of adequate data, especially in the area of cancer incidence and mortality, to demonstrate that regulatory or program intervention has effected any improvement. Regulatory agencies such as Food and Drug Administration can use descriptive epidemiological methods to determine trends in disease and magnitudes of exposed populations largely from readily available data, e.g., mortality data, data from National Cancer Institute surveys, census data, and food consumption data. The goal of these studies is to identify any unexpected changes in incidence or mortality through surveillance of the available data for time trends and through probes of specific data collected during research activities or gathered in support of regulatory decisions. PMID- 4023294 TI - [Massive edema of the ovary. Report of a case]. PMID- 4023295 TI - [Primary squamous carcinoma of the gallbladder. Report of a case]. PMID- 4023296 TI - [Identification of coagulase-negative staphylococci in hospitalized patients]. PMID- 4023297 TI - [Comparative study of the lipid profile in the Panamanian male population]. PMID- 4023298 TI - [Morphine and meperidine. Comparative analysis of their use in epidural analgesia]. PMID- 4023299 TI - [10-year review of biopsies of metastases in the Metropolitan Hospital Complex of the Social Security Administration]. PMID- 4023300 TI - [Ciliary dyskinesia syndrome]. PMID- 4023301 TI - [Evaluation of the chronic lymphocytic leukemias]. PMID- 4023302 TI - [Clinical significance of the enlargement of the descending pulmonary artery in pulmonary embolism]. AB - The authors reviewed chest radiographs of 158 patients with clinical suspicion of pulmonary embolism, subsequently confirmed in 73 and excluded in 85. Right descending pulmonary artery, measured at 4 different levels, was significantly enlarged at acute embolization in respect to either the diameter showed at recovery and the upper normal limit reported in literature. Moreover, the artery was significantly wider in embolic than in non embolic patients. In addition, the shape of this artery was modified in embolism, since the prevailing enlargement of its upper sections caused the artery to take a truncated cone appearance. "Sausage" appearance of the artery, never found in non embolic patients, was specific for embolism. The radiographic width of the descending pulmonary artery enabled also to identify patients most seriously ill, since it showed a positive linear correlation with the degree of perfusion impairment. PMID- 4023303 TI - [Magnetic resonance in the diagnosis of diseases of the brain and spinal cord]. AB - More than 1300 patients have been examined with MR for diseases of the CNS since October 1983. Eight hundred patients were studied with a resistive 0.15 Tesla system and the remaining with a superconductive 0.5 Tesla system. Lesions of the cervical spinal cord, syringomyelia and intra or extra-axial tumors, were perfectly demonstrated. The absence of artefacts in the posterior fossa, as well as sagittal and coronal slices, allow an excellent demonstration of lesions, particularly of brain stem tumors. In a large group of patients with multiple sclerosis, MR has proven to be diagnostically superior to CT, evoked potentials and CSF examination. Sensitivity is very high but specificity may be low in infra and supratentorial gliomas. Differentiation of tumor from oedema may be difficult. PMID- 4023304 TI - [Anomalies of the lumbosacral nerve roots]. AB - Three cases of lumbosacral nerve root anomalies at their emergence are presented. They have been diagnosed by using water soluble non ionic contrast medium myelography. They all belonged to Cannon's type I classification (conjoined roots) and they were all localized at L5-S1 level. The authors emphasize that such anomalies give no symptoms and they underline the importance of their recognition in view of a correct surgical treatment. PMID- 4023305 TI - [Cardiac complications of intravenous digital angiography. Comparison of ionic and nonionic contrast media]. AB - The review of 1405 digital intravenous subtraction angiographies carried out in the period may 1982-february 1985 showed in about 2% of the cases cardiac symptoms, which arose during or after the examination. In the great majority of the cases the symptomatology was characterized by angina pectoris. In order to better understand these data and analysing the results of the literature, a trial has been performed in 100 patients who underwent DSA. They have been divided into two groups in which two different contrast media, ionic (sodium meglumine diatrizoate) and non ionic (iopamidol) have been randomly injected. A detailed cardiologic anamnesis has been collected and EKG has been performed before and after each injection with pre-established gaps. The results showed that the incidence of cardiac symptoms and EKG variations is lesser with the non ionic contrast medium: therefore this agent is to be preferred at least in patients at risk from cardiologic point of view. PMID- 4023307 TI - [2 cases of cryptococcosis]. PMID- 4023306 TI - [A method of quality control in thermoluminescent dosimetry]. AB - This work suggests a quality control method for thermoluminescent dosimetry. For each set of dosemeters, read-out has been made at increasing values of dose, on the base of predetermined conditions in different read-out techniques and from different operators. The statistical analysis of each possible group of T.L.D. permitted us to draw the error-response curves and the relative precision profiles and to select the best evaluation techniques and the best operator on the base of precision, sensitivity and useful range. PMID- 4023308 TI - [Chondromatosis of the temporomandibular joint. Tomographic and CT findings]. PMID- 4023309 TI - [Multicentric reticulohistiocytosis]. PMID- 4023310 TI - [Femoral lengthening by transverse diaphyseal osteotomy. Experimental study in the dog]. AB - Previous work has shown that extensive areas of bone necrosis developed after Z osteotomies of the femoral shaft. A study was made on 11 dogs to compare the effects of a transverse osteotomy followed by immediate lengthening, stabilisation by plates and bone grafting. The bone vitality was studied at 8 and 16 weeks by histological sections and angiography. Attention was focussed on the area of lengthening and the bone ends. The results showed the superiority of transverse osteotomy over Z-osteotomy. Bone necrosis diminished at the 16 th week. In the area of lengthening, the vascularity of the grafts was satisfactory. In contrast, the tendons of the Z-osteotomy showed constant necrosis. PMID- 4023311 TI - [Disepiphysiodesis together with tibial osteotomy in the treatment of Blount's disease. Apropos of 2 cases]. AB - The authors have studied two cases of Blount's disease in girls aged 9. They were treated by operative correction of premature epiphyseal closure, together with tibial osteotomy. In the first case, both procedures were performed simultaneously without hypercorrection, followed by a short period of non weight bearing and was a failure. In the second case, tibial osteotomy was performed first to produce hypercorrection. Division of the premature closure of the medial side of the growth-plate using cement was performed two months later. Weight bearing was not allowed for six months. There was a successful result. It is noted that a combination of tibial osteotomy and lateral epiphysiodesis was followed by a shortening of the limb and must often be repeated several times. The elimination of the premature closure of the medial side of the plate appears to be a better procedure when associated with tibial osteotomy. PMID- 4023312 TI - [Posterior and external transtrochanteric approaches for total hip prosthesis. Comparative study]. AB - 1100 total hip prostheses were inserted between 1977 and 1978. Among them, the authors have selected at random 150 cases operated on by the Austin Moore approach and 150 cases by trochanteric division. The pathology and the type of patient were the same in both groups. A study of the late results showed no difference between the two series. In each, there were two early infections and three late infections. The rate of post-operative dislocation was the same, two early and six late in the Moore approach group, and five early, and two late in the trochanteric division group. There were six sciatic involvements after the Moore approach but only three after trochanteric division, but in this last group there were complications relating to the trochanteric division itself. There were no statistical differences in a comparison of the numbers of re-interventions required. Both techniques appeared to be satisfactory. The Moore approach appeared to be better for the comfort of the patient and does not give any additional risk. Trochanteric osteotomy is indicated in particularly stiff hips, when the greater trochanter has to be displaced downwards or in cases of post operative scarring. PMID- 4023313 TI - [Trochanteric fractures in the elderly: Ender nails, prostheses or direct osteosyntheses. Apropos of a continuous series of 265 cases]. AB - The results of 265 trochanteric fractures in the elderly treated between 1980 and 1983 have been analysed. Among them, 136 were treated by Ender's nailing, 110 by prostheses and 19 by internal fixation. In an earlier study, Ender's nailing had been used in 75 p. 100 of cases. The conclusions were that the increasing use of a prosthesis has brought about an improvement in the results-80 p. 100 satisfactory in the present series compared with 54 p. 100 in the preceding one. The mortality rate was comparable after Ender's nailing and prostheses. Ender's nailing is indicated in stable fractures and, in unstable fractures, internal fixation is indicated in very active persons, Ender's nailing in non-ambulatory patients and prostheses in elderly patients with sufficient walking ability. PMID- 4023314 TI - [Long-term course of lumbar curvature following Harrington instrumentation for thoracic or double major idiopathic scoliosis]. AB - A long-term follow-up study has been made of 276 patients with thoracic or double major idiopathic curves treated by Harrington rodding between 1963 and 1971. 82 patients were able to be followed up to the present date, including 24 double major idiopathic curves and 58 thoracic or thoracolumbar curves. The average follow-up was 15 years with a maximum of 20 years. There were 71 female and 11 male patients. It was concluded that the lumbar curve associated with a thoracic or thoraco-lumbar curve lost about 9.9 degrees when the lower point of insertion of the rod was higher than L3. When it was at L3 or L4 loss of correction was only 3.6 degrees. During the same period the loss of correction of the main grafted curve was 13.6 degrees. In double major curves, the best results were obtained when the lumbar curve was completely or almost completely fused, with an average correction of 17.2 degrees. The results were good when the fixation extended to the apex of the lumbar curve, with an average correction of 11.6 degrees and was moderate when it extended to a higher level with an average correction of 10.9 degrees. It is concluded that in almost all cases, instrumentation needs to be extended to a low level at L3 or L4 to provide greater stability. A study on all 276 cases showed that the morphological adaptation beneath the grafts was satisfactory and long lasting. When the instrumentation stopped at the level of T12, L1 or L2 there was a danger of the development of secondary lumbar kyphosis. Low back pain was not made worse in any cases of low lumbar fixation. PMID- 4023315 TI - [Restoration of elbow extension in the tetraplegic by transplantation of the posterior deltoid. Study of 21 cases]. AB - The authors have transferred the posterior part of the deltoid muscle to the triceps in 21 tetraplegics. A modification of Moberg's technique has been employed utilising a strip of fascia lata reinforced by Dacron sutures to allow rehabilitation after only 3 weeks. Despite limited active extension of the elbow and diminished power, results were considered to be satisfactory by the patients. They benefited from a greater range of movement of the hand, an improved possibility of bearing weight, improvement in the use of wheelchairs and better ability to express their bladder. PMID- 4023316 TI - [Penetrating wound of the leg by a foreign body and arteriovenous fistula. Apropos of a case involving the posterior tibial artery]. AB - The authors report a case of arterio-venous fistula of the posterior tibial artery after a gunshot wound. They emphasise the value of digital arteriography in such cases. Repair of the artery two months after injury was followed by healing. PMID- 4023318 TI - [Unicompartmental arthroplasty (Lotus type) in the treatment of lateralized gonarthrosis in the elderly. Outcome after more than 5 years of 56 prostheses analyzed in 1981]. AB - The progress of 56 uni-compartmental knee arthroplasties has been studied. Five were lost to follow-up after 3 or 4 years: at that time the knees were pain-free and the radiological appearances were good. Seven knees had to be operated on again because of pain after 3.5 years following insertion of the prosthesis. Forty-four prosthesis were still in place after 5 years (average follow-up 6.7 years), 35 of them being almost painless. The knees which became painful did so during the first 3 years and were associated with radiological deterioration. There were 2 loosenings, 11 narrowings of the non-prosthetic tibio-femoral compartment and 3 antero-posterior subluxations with laxity. The authors consider that the main reasons for loosenings were increased stresses and over-correction for narrowing of the non-prosthetic compartment. Subluxation was aggravated by joint obliquity. it is concluded that uni-compartmental knee prosthesis for single compartment arthrosis is a valuable procedure provided that there is good surgical technique and correct indications for operation. However, the long-term prognosis is uncertain because the design of the prosthesis cause increased stresses and some degree of permanent anteroposterior obliquity. PMID- 4023317 TI - [Chiari's osteotomy in adults. Apropos of 72 cases]. AB - The authors have performed 65 Chiari osteotomies in adults. The results have been studied with a follow-up ranging from one to 12 years. Details of the surgical technique are described. Fifty-three cases have had satisfactory results. Forty five cases have a follow-up of more than 5 years and among these, 38 still have a very satisfactory result. It is concluded that Chiari osteotomy may stop the development of early arthrosis clinically as well as radiologically in more than two-thirds of dysplasias or subluxations in patients younger than 50 years. When there is associated femoral dysplasia it should be corrected either simultaneously or preceding the osteotomy. PMID- 4023320 TI - [Multiple myeloma in stage I. Evaluation of the initial therapy]. PMID- 4023319 TI - [In vitro characterization of a group of aplastic anemias]. PMID- 4023321 TI - [Brainstem auditory evoked potentials in Friedreich's ataxia]. PMID- 4023322 TI - [Q fever in Seville. Comparison with other entities. Description of 34 cases and review]. PMID- 4023323 TI - [Fascioliasis hepatica. Review of 5 cases]. PMID- 4023324 TI - [Ataxic hemiparesis caused by a pontine hemorrhage]. PMID- 4023325 TI - [Mucoviscidosis in the adult]. PMID- 4023326 TI - [Acute polymyositis and acute renal failure]. PMID- 4023327 TI - [Severe pulmonary thromboembolism in 3 patients with Behcet's disease]. PMID- 4023328 TI - [Giant aneurysm of the vertebral artery. Description of a case]. PMID- 4023329 TI - [Acute polyradiculoneuritis and herpes zoster]. PMID- 4023330 TI - [Infrequent clinicoradiologic manifestations of acute appendicitis. Presentation of a case]. PMID- 4023331 TI - [Sjogren syndrome. Analysis of 43 patients]. PMID- 4023332 TI - [The blush or flush caused by chlorpropamide/alcohol (CAF) in non-insulin dependent diabetes mellitus]. PMID- 4023333 TI - [Clinico-radiological manifestations of ankylosing spondylitis in the female. Study of 22 cases]. PMID- 4023334 TI - [Schistosomiasis caused by S. haematobium. Apropos of a clinical case]. PMID- 4023335 TI - [Smoldering multiple myeloma]. PMID- 4023336 TI - [Symptomatic cyst of Rathke's pouch]. PMID- 4023337 TI - [Necrosis of the bone marrow in Staphylococcus epidermis sepsis]. PMID- 4023338 TI - [Epidemiology of arterial hypertension in the region of Sierra de San Vicente (Talavera de la Reina, Toledo)]. PMID- 4023339 TI - [Accidental poisoning caused by carbamate insecticides after the ingestion of grapes]. PMID- 4023340 TI - [The decrease of tubercular infection in Spain]. PMID- 4023341 TI - [Arterial hypertension as a manifestation of renal tuberculosis. Apropos of a case]. PMID- 4023342 TI - [Hyperthyroidism associated with leukocytoclastic vasculitis]. PMID- 4023343 TI - [Anesthetic implications of the Spanish toxic oil syndrome]. PMID- 4023344 TI - [Effect of administration of high doses of fentanyl on ADH secretion]. PMID- 4023345 TI - [Incidence of headache and other complications after intradural anesthesia in young patients]. PMID- 4023346 TI - [Importance of protein binding of lorazepam in its clinical management]. PMID- 4023347 TI - [Left ventricular rupture after mitral valve replacement. Description of 2 cases]. PMID- 4023348 TI - [Apropos of a case of pheochromocytoma with difficult to control hypertensive crises]. PMID- 4023349 TI - [Kniest syndrome and anesthesia]. PMID- 4023350 TI - [Extrapyramidal syndrome as an adverse reaction to droperidol]. PMID- 4023351 TI - [Central venous catheterization in experimental studies]. PMID- 4023352 TI - [My concerns and other fantasies]. PMID- 4023353 TI - [Status epilepticus in the adult. Epidemiologic and clinical study in an intensive care unit]. AB - The present study, conducted between January 1975 and June 1983, includes 282 adult patients admitted for status epilepticus (SE) in 2 intensive care units (3.5% of all admissions). In their great majority, i.e., 201, patients had no previous history of epilepsy, and initiated the SE during the course of recent affections such as brain or systemic diseases. In 81 patients with previous seizure, epilepsy was idiopathic in 20, and symptomatic in 61, the 3 main causes being cranial traumatism, cerebrovascular accident and chronic alcoholism. SE was of various causes. The most frequent were cerebro-vascular disease, post-anoxic encephalopathy, intoxication, bacterial or viral meningo-encephalitis. In some patients, SE was preceded by manifestations such as convulsions, behavorial disturbances or conscience impairment. One should be aware of these facts and undertake or increase an anticonvulsivant medication at their onset. Duration of SE, when clearly established, was highly variable but had no apparent correlation to sequelae or death occurrences. SE itself was directly related to death in only 2 cases; in all other instances death was the consequence of the primary disease. These results are consistent with previous reports: presently SE occurs more frequently in the course of other affections than in prior epileptic patients. The better vital prognosis of SE is due to the simultaneous conjunction of new anticonvulsivant medication and supportive care associated with the cure of the causative disease. PMID- 4023354 TI - [Electroclinical study of partial complex epilepsy. Paroxysmal need to drink]. AB - A particular history of a man aged 51 with a right fronto-temporal tumor is analyzed. The main complaint is a paroxysmal need to drink water. Surface electrode electroencephalography and video-telemetry recordings sometimes demonstrated evidence of temporal epileptic abnormalities and therefore seem to have localizing significance. Waterdrinking may thus be added to the widening range of behavioral manifestations associated with epileptic discharges arising in man's temporal lobes. PMID- 4023355 TI - [Value of cassette-recorded long-term 8-channel EEG monitoring in status epilepticus--technical note]. AB - Prolonged EEG-taped recording is a significant recent improvement in technique, with the 8 channels providing the possibility of exploration of the whole scalp. First used for ambulatory monitoring, it was also tested in comatose patients with status epilepticus. The advantages are: the the good quality of the EEGs even after recording continuously for many days, and without drawback for intensive nursing; the help in recognizing infraclinical seizures, often misunderstood by the nursing staff, and the control of treatment; the participation in prospective chronobiological studies. PMID- 4023356 TI - [Extraordinary variant of the alpha rhythm]. AB - The authors describe a variant of alpha rhythm, which is remarkable because of its great amplitude (200-300 microV). It is observed quite exceptionally in children and adolescents with a severe encephalopathy of either ante- or perinatal etiology. They suggest that the surplus amplitude of this alpha rhythm could depend upon a deafferentation of the occipital cortex in patients with severe amblyopia. PMID- 4023357 TI - [Brain stem auditory evoked potentials and chronic alcoholism]. AB - Brain-stem auditory evoked potentials (BAEPs) were obtained from 25 chronic alcoholic patients. The patients had been drinking heavily for an average of 15 years and a minimum of 5 years. All patients were totally abstinent for a minimum of 3 weeks. The morphology of waves were often altered. All presented prolonged I III, III-V, inter-peak latencies (IPLs) and a loss of amplitude of wave V. The I III, III-V and I-VIPLs were increased between 30 and 40 years, and III-V and I VIPLs between 40 and 50 years. The incidence of abnormal BAEPs in patients with alcoholic epilepsy was not different from that of patients without a history of alcoholic seizures. Patients with clinical manifestations of alcoholic polyneuropathy had the highest incidence of abnormal BAEPs. BAEPs are more reliable in chronic alcoholic patients than EEG. The mechanisms of the increase in neural transmission time within the auditory brain-stem are discussed. PMID- 4023359 TI - [Early EEG in 300 cerebral concussions]. AB - The EEGs of 300 concussed patients were examined at the last 48 h after trauma; 166 were younger than 20 years old and 134 were between 20 and 40 years old. Amongst the youngest group 145 cases had a benign concussion with 24% alterations, and 21 cases had a mild concussion with 81% alterations. Amongst the oldest group, 93 cases had a benign concussion with 15% alterations and 41 cases had a mild concussion with 41% alterations. The mostly transient EEG abnormalities are slowing, focal abnormalities or generalized bursts. Slowing is the most frequent abnormality in the youngest and focal abnormalities are most frequently observed in the mild concussion group. PMID- 4023358 TI - [Early brain stem auditory evoked potentials in brain death]. AB - Brain-stem auditory evoked potentials (BAEPs) are realized after the first flat EEG in 50 patients. BAEPs were absent in 70% of the patients. In 22% of the patients, one- or two-sided peak I persists. In 8% the peaks I, II and IV exist after the first flat EEG. BAEP evolution with the course of time is realized. A complete disappearance is established after 24 h. The useful advantage of BAEPs in the early diagnosis of brain death is discussed. PMID- 4023360 TI - [EEG recorded during the 1st 48 hours after a cerebral vascular accident as a result of carotid stenosis]. AB - This article describes the principal EEG abnormalities noted during the first 48 hours of cerebro-vascular ischemic accidents due to carotid artery obstruction. No instances of slow delta waves were seen in the 60 cases of transient ischemic accident. In the 162 cases of cerebro-vascular accidents, all EEG abnormalities were correlated with the level of consciousness and thus add little to the clinical data with respect to the prediction of short-term mortality. However, in the 135 patients who presented a cerebro-vascular accident with no alterations of consciousness, the appearance of polymorphic delta waves or spikes (focalized or diffuse) within the first 48 h does significantly predict short-term mortality. PMID- 4023361 TI - [Value of the sleep EEG as a biological marker of depressive states. Comparison with 3 neuroendocrine tests]. AB - In a sample of 12 endogenous depressive inpatients (8 primary and 4 secondary depressives), we compared the diagnostic usefulness of REM latency (recorded during at least 4 consecutive nights) with 3 neuroendocrine tests: dexamethasone suppression test and GH response after clonidine (a alpha-adrenergic agonist) and apomorphine (a dopaminergic agonist) challenges. Shortened REM latency (less than 50 min during at least 1 night) was present in 67% of depressives. However, REM latency presented a clear night to night intra-patient variability that makes it necessary to record at least 3 consecutive nights for the best sensitivity. Non suppression after dexamethasone was present in 50% of depressives, blunted GH response after clonidine, in 75% and blunted response after apomorphine, in 42%. A total of 92% of patients exhibited at least one abnormal biological parameter (100% of primary and 75% of secondary depressives); 67% of patients exhibited at least two disturbed parameters and these patients constituted the whole primary depressive group (100%). These results show that these 4 potential biological markers of depression are not necessarily distributed in the same population. This suggests the potential usefulness of their concurrent use for improved accuracy of diagnosis. PMID- 4023362 TI - New type of electrode for clinical EEG. AB - The author describes a new type of small electrode for clinical electroencephalography. This practical electrode, constructed on the same principles as a felt tip pen, assures a good contact without conducting paste and gives excellent results. PMID- 4023363 TI - [Ambulatory EEG monitoring (Medilog 9000). Initial results in a pediatric population]. AB - The authors report their experience of ambulatory EEG monitoring (Medilog 9000, Oxford Instruments) in a paediatric population. They describe the method of recording, the system of lecture and the paper reproduction possibilities. Thirty four 24 h cassettes have been recorded and analysed in 30 children aged from 1 month to 17 years. Six infants (under 1 year) had convulsions or spasms; 20 children were epileptic and 5 children were recorded for different reasons. Sleep was obtained in all cases. Seizures were recorded in 5 of 6 infants under 1 year of age, and in 11 of 20 epileptic children. The advantages and applications of this method are discussed. PMID- 4023364 TI - [Scanning electron microscopy in carcinoma of the gallbladder]. PMID- 4023365 TI - [Gastric hypersecretion and duodenal ulcer: suspected existence of a non-gastrin secretagogue through bioassay]. PMID- 4023366 TI - [Detection and bloodless control of postoperative biliary reflux. Apropos of 25 cases]. PMID- 4023367 TI - [Gastric cancer after vagotomy and drainage for peptic ulcer]. PMID- 4023368 TI - [Effects of various calcium antagonists on the muscular activity of the guinea pig ileum]. PMID- 4023369 TI - [Cellular and humoral immunity in chronic intestinal inflammatory disease. Our results with an in vitro test]. PMID- 4023370 TI - [Usefulness of acute phase reactants and albumin in the diagnosis of Crohn disease]. PMID- 4023371 TI - [Surgical problems in cancer of the pancreas and ampullar region (apropos of 84 cases)]. PMID- 4023372 TI - [Gastric leiomyosarcoma]. PMID- 4023373 TI - [Obstructive icterus presenting as a form of tuberculosis disease]. PMID- 4023374 TI - [Reduction of oxygen consumption and capillary obstruction by megakaryocytes in the cerebral cortex of rats with portocaval shunts]. PMID- 4023375 TI - [Treatment of peptic narrowing of the esophagus by vagotomy, partial gastrectomy, and Roux's gastrojejunal "Y" anastomosis]. PMID- 4023376 TI - [Transduodenal sphincteroplasty]. PMID- 4023377 TI - [Liver involvement in little-known virus diseases]. PMID- 4023378 TI - [Mirizzi's syndrome. Presentation of 2 cases]. PMID- 4023379 TI - [Pancreatic lithiasis and cancer of the pancreas]. PMID- 4023380 TI - [Single ulcer of the colon. Report of 3 new cases]. PMID- 4023381 TI - [Chronic idiopathic eosinophilic pneumopathies. A study of 16 cases]. AB - We report 16 cases of chronic idiopathic interstitial pneumonia (P.C.I.E.). P.C.I.E. has well defined clinical, radiological and biological characteristics which enable the eosinophilic pulmonary infiltrates to be recognised and the diagnosis to be confirmed without histological proof. The data from broncho alveolar lavage (L.B.A.) show that besides the radiological infiltrates, there is a diffuse alveolar eosinophilia; sometimes confirming the pulmonary function results, which show a similar pattern to diffuse interstitial pneumonia (P.I.D.). The frequent association of asthma (50%) and extra-pulmonary signs (30%) may suggest a vasculitis or more particularly the Churg-Strauss syndrome, all the more so without a lung biopsy; however the evolution of the disease and the response to low dose steroid therapy is against the latter two being considered in the differential diagnosis. The prognosis for P.C.I.E. is good in the short and medium term; nevertheless during the period under observation (mean 6.3 years) steroid therapy could only be stopped in 3 out of 16 patients. The other patients were stable with a low dose of Cortisone. No patient with P.C.I.E. associated with asthma or hypergammaglobulinaemia or extra-pulmonary signs could be weaned from steroids. The authors advocate that the dose of steroids should be adjusted as low as possible to maintain an eosinophilia below 500/mm3. PMID- 4023382 TI - [Bronchial cancer in miners from the coal beds of the Lorraine basin]. AB - The present study examines the mortality levels from primary bronchial cancer in the miners of Houillieres du Bassin de Lorraine, including pneumoconiotics and non-pneumoconiotics aged more than 45. 48, or 8.87% of deaths of known cause occurring between 1977 and 1981 amongst pneumoconiotics were due to a primary bronchial cancer, proved cytologically and histologically. This level did not differ from that of 7.66% seen in 796 coal miners who had worked for more than 15 years underground and unscathed by any occupational disorder, nor for the 8.57% level of men residing in the Moselle department. It is, on the other hand, significantly elevated versus the 6.34% of Frenchmen for the same age range. Tobacco consumption and industrial atmospheric pollution in the Moselle is more important than in most other French departments and should be considered when interpreting this excess mortality for bronchial cancer in this department when compared to the french national average. For the coal miners of Lorraine this study had not established a correlation between the work, the pneumoconiotic lesions and the frequency of primary bronchial cancer. PMID- 4023383 TI - [Diffuse familial interstitial pulmonary fibrosis. Study of a family]. AB - A study of the genealogy of a 53 year old lady (A.M...) suffering from diffuse interstitial pulmonary fibrosis (FID) has revealed several cases of FID in her forbears and relations. Two brothers of A.M... died of histologically proven FID; FID was also discovered in one of their daughters. A sister died young of some unclassified respiratory problem. Two cousins died likewise at a young age of acute FID proven histologically. The level of spontaneous pneumothorax was particularly elevated in this family which represented a clinical peculiarity when compared to sporadic FID. The most probable mode of transmission of familial FID is autosomal dominant with variable penetrance. The HLA group seen in A.M... showed the A2 and B12 alleles. The B12 allele was also present in the niece of A.M... PMID- 4023384 TI - [Pneumopathy caused by hypersensitivity to isocyanates. Value and dangers of a realistic provocation test]. AB - Organic isocyanates are responsible for bronchial pathology and in rare cases of hypersensitivity pneumonia. We present a new observation supported by a complete lung function assessment, histology of a transbronchial biopsy and a positive bronchial challenge test. The progress of the disorder was followed by repeated lung function measurements and bronchoalveolar lavage. The alveolar response at first showed an alveolar leukocytosis, then a mixed picture, finally becoming a pure lymphocytosis. The activity of the alveolar cells was assessed for T lymphocytes by cytofluorimetry, the presence of DRa like and LMR antigens and lastly for macrophages with Gallium scans. The inflammatory response was followed by analysing the proteins in the lavage liquid. The value of studying alveolar cell-activity and equally alveolar protein content is underlined in this study and reminds one of the character, sometimes unpredicted and dangerous, of challenge tests using isocyanates. PMID- 4023385 TI - [Long-term treatment of chronic respiratory insufficiency using endotracheal ventilation at home in 118 tracheotomy patients]. AB - 118 patients suffering from severe chronic respiratory failure were submitted to domiciliary artificial ventilation (V.A.D.T.) by tracheotomy using a fixed rate volumetric respiration. The daily length of V.A.D.T. was 10 to 16 hours. The improvement on the blood gases, their stability, the disappearance of signs of right heart failure and polycythaemia, as well as a large reduction in mean length of hospital stay per subject and per year after V.A.D.T., underlined the efficacy of this method. In the long term (10 years) there was a 50% survival in patients with restrictive respiratory failure and of 33% in subjects with a mixed respiratory failure, which was predominantly restrictive. It was lower with mixed respiratory failure that was predominantly obstructive (20%). No patient with isolated airflow obstruction survived more than six years. PMID- 4023386 TI - [Value of tracheobronchial endoscopy in facial burns]. AB - 41 patients suffering from facial burns had a systematic tracheo-bronchial endoscopy in the 24 hours after admission to hospital. There were 21 cases of explosion (town gas or explosives), 11 burns from flames (petrol) and 9 burns occurring during fires (in houses or cars). 12 patients showed isolated mucosal inflammation, 5 blackish deposits (of impacted soot) and blisters in 6 (with shreds of mucosa hanging loose); the endoscopy was normal in 18; 66% of those with blisters (4 cases out of 6) and 40% with blackened mucosa (2 cases out of 5) were observed in burns from fires. The 18 patients without endobronchial lesions and 12 patients with only mucosal inflammation did not develop respiratory complications; 5 patients presenting with blackish deposits later develop complications and 4 out of 6 patients presenting with extensive blistering died from these respiratory complications. A study of the evolution of the lesions, as far as could be ascertained from several cases enabled the rules of local therapy to be set in such patients: aspiration and unblocking of the airways by repeated aspiration and lavage. In conclusion, the frequency of tracheo-bronchial lesions and their significance when planning therapy and their consequences on the prognosis justify tracheo-bronchial endoscopy to be used routinely in burns to the face. PMID- 4023387 TI - [Agranulocytosis caused by ticlopidine]. PMID- 4023388 TI - [Changes in the lymphocyte subpopulations in type 1 diabetes mellitus]. PMID- 4023390 TI - [Mast cells and rheumatoid synovitis]. PMID- 4023389 TI - [Significance of the ST segment depression in precordial leads in lower myocardial infarct]. PMID- 4023391 TI - [Rifamycin and superoxide dismutase in the treatment of rheumatoid synovitis of the knee]. PMID- 4023392 TI - Production and excretion of dopamine by the isolated perfused rat kidney. AB - Renal catecholamine concentrations and urinary dopamine excretion from the isolated perfused kidney were measured in intact and peripherally sympathectomized rats. Urinary dopamine excretion was not diminished by sympathectomy, was increased by l-dopa (but not tyrosine or dopamine 4-O sulphate) in the perfusate and was virtually abolished by prior treatment with the dopa decarboxylase inhibitor, carbidopa. These results confirm the importance of renal extraneuronal dopamine production, from circulating l-dopa, as a contributor to urinary dopamine excretion. PMID- 4023393 TI - Inhibitory effect on lithium on p-aminohippurate transport in rat kidney cortex in vitro. AB - The effect of lithium on p-aminohippurate (PAH) transport was studied using slices and basolateral membrane vesicles prepared from rat kidney cortex. The addition of lithium in concentrations ranging from 0.5 to 5 mM caused a concentration-dependent inhibition of PAH accumulation in the slices. Lithium inhibited PAH accumulation in the slices, not only during the rapid uptake period (after 10 min) but also during the approach to equilibrium (after 30 min). The effect of lithium (2 mM) in the slices was irreversible. The inhibitory effect of lithium was not the result of changes in the water distribution and the concentrations of ATP, sodium and potassium in the slices during incubation. The effect of lithium on the kinetic parameters for PAH accumulation was to decrease Vmax, while apparent Km remained constant. There was no lithium effect on the efflux of PAH from the slices back into the incubation medium, indicating that lithium inhibited PAH influx to the kidney cell. No evidence was obtained to indicate that lithium (1 mM) directly affected PAH uptake by isolated basolateral membrane vesicles. These results suggest that lithium seems to affect metabolism linked to the carriers for PAH transport other than ATP production and sodium gradient and then seems to decrease the mobility of the carriers in the membranes. PMID- 4023395 TI - [Postnatal development of the fatty acid composition of lipids of adipose and muscle tissue in rabbits on a low-fat diet]. AB - The relative fatty acid profiles of perirenal adipose tissue and muscle tissue of the hind legs were studied in New Zealand rabbits 21 to 140 days old. The rabbits were fed a low-fat diet covering the essential fatty acid requirements and distributed either ad libitum or in rationed amounts. The whole of the fatty acids were established earlier in hind leg muscle tissue than in perirenal adipose tissue. In the latter, the growth allometry of fatty acids in relation to the carcass was already higher between 21 and 74 days (a = 1.39) and distinctly higher between 74 and 140 days (a = 2.68). In the muscle tissue, an isometric phase (a = 0.96) preceded a major allometric phase (a = 1.76). In young suckling rabbits, the fatty acid profile of perirenal lipids was influenced by that of the milk lipids. In the muscle tissue, the presence of a large proportion of phospholipids resulted in a higher percentage of stearic acid and polyunsaturated fatty acids of the (n-6) family (linoleic, dihomo-gamma-linolenic and arachidonic acids). After weaning, the proportion of saturated fatty acids (C greater than or equal to 14) in the perirenal adipose tissue remained constant. The endogenous production of monounsaturated fatty acids (higher allometry) caused a progressive dilution of polyunsaturated fatty acids (lower allometry). This dilution was slowed down when the diet was rationed. Changes in the fatty acid composition of muscle tissue were, in general, comparable to those of perirenal adipose tissue. The differences observed could be attributed to the more active participation of phospholipids in the total lipids of the muscle tissue. Stearic acid, abundant in the phospholipids, showed a lower allometry compared to total fatty acids. Its dilution was an expression of triglyceride dilution of the phospholipids during growth. The same was true of polyunsaturated fatty acids. Rationing had the reverse effect. PMID- 4023396 TI - Zona-free hamster ovum penetration by human spermatozoa: influence of various sperm factors. AB - The present paper evaluates the influence of various technical factors when preparing human spermatozoa to be tested for their ability to penetrate zona-free hamster ova. Higher in vitro fertilization rates were obtained after sperm selection by "swim-up" migration, 4-h incubation, sperm dilution to a concentration of 2.5 X 10(6) spermatozoa/ml, and observation of the oocytes 8 h after insemination. The use of control samples was necessary because of wide intraindividual and interindividual variations in the results. Unless the result has been confirmed several times, it is impossible to conclude, from a negative test, that a human spermatozoon cannot penetrate a hamster oocyte. PMID- 4023394 TI - In vivo milk digestion in the calf abomasum. III. Amino acid compositions of the digesta leaving the abomasum. AB - Calves were fed five different test meals: whole milk, skim milk, 3% whole casein solution, 3% whole casein in simulated milk ultrafiltrate, and whey. The digesta leaving the abomasum before feeding and during the first 7 postprandial hours were collected by fractions. After precipitation with 12% TCA, the amino acid compositions of the sediments and the supernatants were determined and compared by multivariate analysis. The composition of prefeeding digesta was similar to that of gastric juice. When the calves were fed the two casein diets, the amino acid composition of the sediments changed little with time. In contrast, the changes observed in the composition of the supernatants suggested rapid abomasal emptying of caseino-macro peptide. With the whey diet, it was not possible to evidence more rapid hydrolysis or abomasal emptying of any particular whey protein. During the first 10 min following the ingestion of whole or skim milk, the amino acid composition of the sediment was close to that of milk protein. Immediately afterwards, the composition of the sediment was similar to that of whey protein. Thereafter, the composition of the sediment became more like that of casein and almost reached that of casein during the 7th hour. The amino acid composition of the supernatant was similar to that obtained with the casein diets; this fact suggests that the small peptides produced by proteolysis in the abomasum originated more from casein than from whey proteins. PMID- 4023397 TI - Neonatal levels of plasma thyroxine in male and female calves fed a colostrum or immunoglobulin diet or fasted for the first 28 hours of life. AB - The effect of diet on changes in plasma thyroxine levels was studied in 83 newborn Friesian X Holstein calves. Fifty-four received four copious meals of first-milking colostrum at 4, 10, 16 and 22 neonatal hours. At the same time, 24 animals received four meals of a solution of colostrum immunoglobulins containing little energy, and 5 calves were kept fasted. The last two treatments resulted in lower plasma thyroxine levels than those in colostrum-fed calves. At the same time, plasma thyroxine level was higher in females than in males during the first neonatal week. PMID- 4023398 TI - Ketone body metabolism during pregnancy in the rabbit. AB - The aim of this study was to test the effect of lipid store mobilization on changes in ketone body metabolism in pregnant rabbits. Related blood parameters were studied in pregnant animals fed either ad libitum or submitted between days 21 of gestation and parturition first to 50% food restriction for 4 days and then to a complete fast. Ketogenesis from oleate, butyrate and endogenous substrates was measured on days 0, 8, 18 and 28 of gestation in isolated liver cells prepared from females fasted for 48 h. In the does fed ad libitum, the concentration of non-esterified fatty acids (NEFA) was higher than in non pregnant animals and then increased about 2-fold in the last week before term. Total ketone body concentrations increased slightly but significantly from day 27 until term. In the same period, glycemia decreased significantly. No variations were observed in lactate, alanine and total amino acid concentrations. Food restriction on days 21 to 24 induced a quick rise in the plasma concentrations of NEFA, ketone bodies and glycerol. Further fasting resulted in the development of hyperketonemia which was more than 3 times that observed during prolonged fasting in non-pregnant rabbits. There was no further increase in plasma NEFA level after day 27 of gestation. Food restriction and fasting decreased only the plasma level of total amino acids but had no significant effect on plasma concentrations of lactate and alanine. In isolated liver cells, a marked and significant increase in the rate of ketogenesis from oleate, butyrate and endogenous substrates was noted on day 28 of gestation in comparison with the preceding periods. It is concluded that ketonemia was enhanced in late gestation, particularly with restricted feeding or in fasted animals; this enhancement was partly related to the increase of plasma NEFA concentrations and partly to the enhancement of hepatic ketogenesis in the mothers. The fact that the rate of hepatic ketogenesis was increased equally with butyrate and oleate indicated that it could not be explained by a modification of acylcarnitine transferase activity as butyrate directly crosses the mitochondrial membrane without using this pathway. PMID- 4023399 TI - Incidence of (n-3) essential fatty acid deficiency on trout reproductive processes. AB - A feeding experiment was conducted on rainbow trout broodstock for one year to investigate the influence of the quality of dietary lipids on egg and fry fatty acid composition, embryonic development and hatching efficiency. The broodstock were fed either a commercial control diet or a (n-3) fatty acid-deficient diet; their liver, eggs and fry were analysed to determine the fatty acid composition of their neutral and polar lipids. The fatty acid pattern in liver, eggs and fry was markedly different due to the qualitative difference of the dietary lipids. The most striking difference was the low amount of 22:6 (n-3) and the high levels of 20:4 (n-6) and 22:5 (n-6) in phospholipids of fish receiving the (n-3) deficient diet containing a high level of 18:2 (n-6). While fertilization efficiency was equivalent in the first two days of development, whatever the diet, two peaks of mortality were observed, one at day 8 and the other at day 22 after fertilization, during the time the eggs produced by the deficient fish were incubated. A shorter period of vitellus resorption (50 vs 65 day) was observed in (n-3)-deficient alevins as compared to controls. Morphological study of the development of the (n-3)-deficient embryos showed some cleavage disorders at the 16 to 32-cell stage, a blocking effect before gastrulation, and later various alterations in organogenesis. It was concluded that (n-3) fatty acids, and especially 22:6 (n-3), play a crucial and specific role in trout embryo development. These fatty acids could be involved in cellular recognition processes through their oxygenated derivatives. The need for long-term nutritional deficiency to induce the reported biochemical and physiological alterations is discussed. PMID- 4023400 TI - Determination of local cerebral glucose metabolism in humans: methodology and applications to the study of sensory and cognitive stimuli. PMID- 4023401 TI - Patterns of cerebral glucose utilization in depression, multiple infarct dementia, and Alzheimer's disease. AB - Patterns of local cerebral glucose utilization were determined in moderately to severely disabled patients with D (N = 7), MID (N = 6), and AD (N = 6), and in normal controls (N = 6), using positron emission tomography with the 18F fluorodeoxyglucose method. Average global metabolic rate was decreased 30% in patients with AD, but overlap among the other groups reduced the discriminant value of this measure. In depressed patients, the cerebral metabolic pattern was normal, except for evidence of hypometabolic zone in the posterior-inferior frontal cortex which was of marginal statistical significance. In MID, focal metabolic defects were scattered throughout the brain and exceeded the extent of infarction. In AD, metabolism was markedly reduced in cortex, especially parietal cortex, but relatively preserved in caudate, thalamus, anterior cingulate gyrus, pre- and post-central gyrus, and calcarine occipital cortex, a pattern duplicating the degree and location of pathological and neurochemical alterations characteristic of this disorder. PMID- 4023402 TI - Principles of imaging structure by NMR. PMID- 4023403 TI - Magnetic resonance imaging of the central nervous system. AB - Clinical MRI of the CNS has evolved rapidly. The image quality has now surpassed CT in depicting anatomical detail. It is more sensitive than any other imaging modality, including CT, in the detection of disease. The specificity of MR is at least equivalent to CT, and as the learning curve improves and a broader base of information is acquired as to the relative utility of different imaging parameters and the applications of T1 and T2 measurements, it is hoped that specificity will improve as well. There is little question that in the cooperative patient MR will displace CT scanning as the primary screening modality in the patient with CNS disease in whom an imaging technique is appropriate. PMID- 4023404 TI - Continuous noninvasive organ biochemistry and NMR imaging of brain. PMID- 4023405 TI - Metabolic mapping of the primary visual pathway. PMID- 4023406 TI - Applications of brain blood flow imaging in behavioral neurophysiology: cortical field activation hypothesis. AB - The 133xenon intracarotid method for rCBF measurements has been a very useful method for functional mapping and functional dissection of the cerebral cortex in humans. With this method it has been shown that different types of cortical information treatment activate different cortical areas and furthermore that sensory and motor functions of the cerebral cortex could be dissected into anatomical and informational subcomponents by behavioral manipulations. The brain organizes its own activity. One of the principles of organization was that the brain could recruit in advance cortical fields that were expected to participate in a certain type of information operation. During brain work in awake human beings the cerebral cortex was activated in fields that, projected on the cerebral surface, most often had a size greater than 3 cm2. Such activated fields appeared no matter which type of information processing was going on in the brain: during planning and execution of voluntary movements, during preparation for sensory information processing, and during sensory information processing, as well as during cognitive brain work and retrieval of specific memories. Therefore, it was hypothesized that cortical field activation was the physiological manifestation of normal brain work in awake humans. PMID- 4023407 TI - A comparison of in vivo and in vitro amphetamine on the synaptosomal uptake of dopamine in mouse striatum. AB - Amphetamine (AMPH) produced competitive uptake inhibition of 3H-dopamine (DA) in synaptosomes obtained from mouse striatum--whether it was injected beforehand into living animals or simply added to the incubation medium. However, the in vivo drug doses required to produce this effect were high (ED50 = 65 mg/kg.) as compared with the in vitro doses (ED50 = 2.5 X 10(-6) M). PMID- 4023408 TI - Comparison between locomotor activity changes produced by phencyclidine and D amphetamine in CD-1 male mice. AB - Comparative studies were pursued to investigate the locomotor activity induced by phencyclidine hydrochloride in CD-1 male mice. Horizontal, vertical, and rotational activity counts were quantitated using an infrared beam animal activity monitor. Five doses (1.5, 2.5, 3.5, 5.0, and 10.0 mg/kg, i.p.) of phencyclidine were compared. At the 1.5 mg/kg dose, no locomotor activity changes were observed when compared to a saline control group. Increased activity was observed at the 2.5, 3.5, and 5.0 mg/kg doses. Decreased activity was observed at the 10.0 mg/kg dose when compared to the 5.0 mg/kg dose possibly due to ataxia. In addition, the locomotor activity produced by acute d-amphetamine and acute phencyclidine was compared at doses of 2.5 mg/kg and 5.0 mg/kg respectively. The overall locomotor activity levels produced by acute d-amphetamine and phencyclidine were not significantly different at p less than 0.05. The time to peak activities and peak level activities were also similar and occurred at 20-25 minutes and 1100-1300 inches respectively after i.p. administration. Administration of apomorphine after phencyclidine did not change overall locomotor activity. The data implies that phencyclidine may act primarily as a dopamine reuptake inhibitor rather than a dopamine release stimulator. Phencyclidine also affects other activity (unlike amphetamine) as seen by the severe depression of vertical activity. PMID- 4023409 TI - Effect of a specific tetrahydroisoquinoline on the blood pressure in animals. AB - 1-(2-Methyl-3-hydroxy-5-hydroxymethyl-4-pyridyl)-6,7-dihydroxy-1,2, 3,4 tetrahydroisoquinoline (PTIQ) when injected into anesthetized normotensive minipigs and dogs lowers the arterial blood pressure in a dose-related manner. The blood pressure lowering effect of PTIQ is greater on minipigs than dogs at comparable dose levels. The heart rate is generally slower after PTIQ was injected than the control. PMID- 4023410 TI - Experimental cerebral infarction in Mongolian gerbils: effects of vincamine on lesion size, survival and behavior. AB - Vincamine was administered to gerbils at doses of 0, 1, 2, 10 and 40 mg/kg/d to study its effect on survival, extent of ischemic brain lesion, locomotor activity, neurologic signs, stool production, and food and water intake after unilateral carotid occlusion. Drug and placebo were delivered by implantation of osmotic minipumps. The three most important criteria, increase in survival, reduction in cerebral lesion in survivors, and functional recovery of locomotor activity were all significantly improved by vincamine treatment at all doses. Since the lowest dose produced as much improvement as the higher doses it was concluded that increasing dose beyond 1 mg/kg/d was not beneficial using the measures reported here. PMID- 4023411 TI - A readily obtainable analog of propranolol suitable for use as internal standard in chromatographic assays for propranolol. AB - There appears to be a need for a readily and conveniently available close chemical analog of propranolol suitable for use as internal standard in a variety of chromatographic assays of the drug. With this purpose in mind, we developed a simple procedure for the preparation of N-cyclopentyldesisopropylpropranolol. The commercially available and inexpensive starting materials are mixed in a flask and after 48 hr at room temperature the precipitated product is filtered off. Mass spectrometry, melting point determinations, and elemental analysis were used to characterize the product. N-cyclopentyldesisopropylpropranolol was used as internal standard in a liquid-chromatographic assay of ten replicate 50 ng/ml propranolol plasma samples, and gave a coefficient of variation of 3.4%. PMID- 4023412 TI - The inhibition of mitochondrial respiration by indomethacin, a non-steroid anti inflammatory agent possessing inhibitory effect on prostaglandin biosynthesis. AB - It was found that indomethacin, a potent inhibitor to cyclo-oxygenase in prostaglandin biosynthesis system, disturbed mitochondrial respiration and its farnesyl ester, E-0710 which no longer exhibited the inhibitory effect on cyclo oxygenase, did not affect the mitochondrial respiration, indicating a good correlation between the inhibitory effect on ATP biosynthesis in mitochondria and the anti-inflammatory activity of indomethacin. PMID- 4023413 TI - Liver regeneration and hepatic microsomal enzyme induction by acetaminophen and derivatives. AB - Liver regeneration was stimulated in male rats with two-thirds of the liver removed by feeding a basal diet supplemented with acetaminophen (0.35-1.5%; weight basis), 2-acetamidophenol (1.0%) and acetophenetidin (1.0%) over a period of 10 days po, but was in the control range with the m-isomer, 3-acetamidophenol (1.0%), N-butyryl-p-aminophenol (1.0%), o-, m- and p-aminophenols (0.50%) and 4 acetamidothiophenol. In fact, the latter inhibited at a level of 0.60%. The operated young or mature female underwent no significant increase in control response with acetaminophen (1-1.5%). However, as with the male, the wet and dry liver weight percentages were markedly increased in the intact female fed acetaminophen (1.0-1.5%) as also with 2-acetamidophenol (1.0%). Liver enlargement occurred in the intact male with acetophenetidin (1.0%) but not with the N butyryl- and thiophenol derivatives fed at 1.0 and 0.50%, respectively. Hepatic microsomal preparations from the intact and operated series showed no remarkable changes in cytochrome P-450 nor in the enzymes, aminopyrine demethylase and benzo[a]pyrene hydroxylase, with the more polar acetaminophen and the N-butyryl compound but the enzymes were elevated in the group fed acetophenetidin. Inductive effects on microsomal enzymes were further amplified by injection of several animals per group with phenobarbital ip daily at 80 mg/kg for the last 3 days prior to sacrifice. Increases in increments or liver weight percentages ensued over the basal values and as investigated in an intact male series, the enzymes ranged higher than the uninjected controls and with the thiophenol-fed group, exceeded those of the phenobarbital-injected controls. PMID- 4023414 TI - Efficacy of sulfhydryl compounds as inhibitors of iron-dependent doxorubicin enhanced lipid peroxidation. AB - The ability of sulfhydryl compounds to inhibit doxorubicin enhanced lipid peroxidation in the presence of added iron was evaluated. Optimal conditions for doxorubicin-enhanced lipid peroxidation were 25 microM doxorubicin, 2 mM ADP and 250 microM ferric chloride at pH 8.0. Lipid peroxidation was inhibited by EDTA (500 microM), SKF 525 A (100 microM) and vitamin E (0.1 unit/ml). Cysteamine (1 mM) stimulated basal lipid peroxidation but produced net inhibition of lipid peroxidation with doxorubicin. Cysteamine (10 mM) was more efficacious at inhibiting lipid peroxidation. N-acetylcysteine at 1 and 10 mM was a potent stimulator of lipid peroxidation and was ineffective at inhibiting lipid peroxidation in the presence of doxorubicin either at optimal or suboptimal concentrations of iron. In contrast, glutathione (1 mM) was a potent inhibitor of lipid peroxidation. The data suggests that N-acetylcysteine protects against doxorubicin by prior conversion to glutathione. PMID- 4023415 TI - Effects of calcium and verapamil on normal and tumor murine leukocytes. AB - Although no differences in membrane stabilization by calcium were noted between leukemic (P-388) and normal murine leukocytes, tumor cells were shown to be more resistant to damage by ethanol but not by desmethylchlorpromazine. Furthermore, verapamil protected tumor cells but not normal cells against the disruptive effect of desmethylchlorpromazine but not that of ethanol. The protective action of verapamil was evident even in the absence of calcium. Thus leukemic cells appear to be altered so that the effects of certain membrane active agents are changed but the membrane stabilizing function of calcium is normal. PMID- 4023416 TI - Cardiotonic agents: a simple HPLC procedure for the quantitation of dobutamine and a new congener in plasma. AB - A simple high performance-liquid chromatographic procedure employing electrochemical detection (LC-EC) has been developed for the quantitation of the cardiotonic agent dobutamine and a new pharmacologically active congener. The drugs were extracted from plasma by adsorption on to alumina, eluted from the adsorbent with dilute perchloric acid and the eluate subjected to LC-EC. The method had a limit of sensitivity of 1 ng/ml of plasma for each drug. The applicability of the LC-EC procedure was demonstrated by determining steady-state plasma concentration profiles of dobutamine and its congener in man and dog, respectively, following i.v. infusion of the drugs. PMID- 4023417 TI - The effects of short-term administration of ibuprofen on trimethadione metabolism and antipyrine metabolite formation in the rat. AB - In this study, trimethadione (TMO) was chosen as a model drug to investigate the extent of hepatic drug-oxidizing capacity. It was also studied whether pretreatment of rats with ibuprofen selectively affected the formation of antipyrine metabolites. The ratios of serum dimethadione (DMO)/TMO and the urinary metabolite formation of antipyrine in the rat pretreated with ibuprofen 50 mg/kg daily for 7 days were not changed as compared to controls. These results indicate that the short-term administration of ibuprofen did not impair TMO metabolism and changed antipyrine and its metabolite formation in the rat 24 h urine. PMID- 4023418 TI - Comparison of [3H]nicotine and [3H]acetylcholine binding in mouse brain: regional distribution. AB - In a continuing study of nicotine binding sites, we determined the relative amount of nicotine binding and acetylcholine binding in various brain regions of C57/BL and of DBA mice. Although midbrain showed the highest and cerebellum the lowest binding for both [3H]nicotine and [3H]acetylcholine, the ratio of nicotine to acetylcholine binding showed a three-fold regional variation. Acetylcholine inhibition of [3H]nicotine binding indicated that a portion of nicotine binding was not inhibited by acetylcholine. These results indicate important differences between the binding of (+/-)-[3H]nicotine and that of [3H]acetylcholine. PMID- 4023419 TI - High performance liquid chromatographic determination of cyclosporin A in body fluids. AB - A sensitive, specific and reproducible high performance liquid chromatographic assay method for the determination of a new immunosuppressant, cyclosporin A (CsA), in the biological samples such as human blood, rat plasma and rat lymph has been developed. CsA was extracted with diethyl ether followed by being cleaned up with liquid-liquid extraction procedure using carbon tetrachloride methanol system, and was chromatographed on a microparticulate CN column with UV detection at 212 nm. The lower detection limit is 100 ng/ml in human blood (from 1.0 ml) and 500 ng/ml in the rat plasma or lymph (from 0.2 ml). This method is sensitive enough for monitoring CsA concentrations in the renal transplant patients in the therapeutic dose range, and is also applicable to the determination of CsA in the rat plasma and lymph samples for the purpose of pharmacokinetic evaluation of several CsA dosage forms in the rats. PMID- 4023420 TI - Pharmacological actions of diaspirins, potential antisickling agents: analgesic and anti-inflammatory effects. AB - Three aspirin analogs, dibromoaspirin, bis(3,5-dibromosalicyl) succinate and bis(3,5-dibromosalicyl) fumarate, potential antisickling agents, were compared with acetylsalicylic acid (aspirin) for their analgesic, body temperature and anti-inflammatory effects in the laboratory mouse and rat. In the analgesic assay, using the "writhing method", only a 200 mg/kg dose of the diaspirin succinate significantly reduced the writhing response induced by phenylacetic acid. Only a dose of 800 mg/kg of acetylsalicylic acid significantly decreased writhing. These analog compounds had only slight hypothermic effects, the reduction in body temperature not being appreciable. On the other hand, they were effective anti-inflammatory agents, comparable to aspirin; a dose of 200 mg/kg very significantly reduced the paw edema due to injected carrageenan. PMID- 4023421 TI - Response of uroporphyrinogen decarboxylase to the hematopoietic demands of the spleen. AB - Uroporphyrinogen (urogen) decarboxylase was studied in rat spleen before and after stimulation of splenic hematopoietic cell synthesis with phenylhydrazine (PHZ). Urogen decarboxylase activity was increased over 2-fold following PHZ treatment concomitantly with a comparable increase in spleen weight. The increase in enzyme activity could not be attributed to a direct effect of PHZ on endogenous urogen decarboxylase nor to production of a specific activator of the enzyme in spleen cells. Moreover, the increase in urogen decarboxylase activity following PHZ administration was completely prevented by concomitant treatment with cycloheximide. These findings suggest that urogen decarboxylase activity in spleen represents endogenous porphyrin synthesizing capacity of that tissue, rather than that of sequestered erythrocytes undergoing destruction in that organ. Additionally, they suggest that the capacity for porphyrin synthesis in the spleen is highly responsive to chemically-induced demands for hematopoietic activity. PMID- 4023422 TI - Hepato- and neuro-toxicity by ethylenthiourea. AB - Thyrotoxicity of Ethylenthiourea (2-imidazolidinethione) (ETU) is well known: this paper examines the extent to which ETU alone may damage certain non-thyroid tissues, and the possible enhancement of its effects through synergism when it is taken with substances employed for medical or alimentary reasons. It was found that the lethality of ETU is augmented by accumulation of fractionated doses, particularly in male as opposed to female rats. When accompanied by ethanol, its harmfulness is increased, whereas phenobarbital provides a certain degree of protection. Liver secretion of triglycerides is greatly impaired (delta % = -31) by acute administration, which results in steatosis. This is not observed during subacute administration. Liver microsomal cytochrome P450 is significantly reduced (delta % = -32) after a long term administration. The 30 week treatment leads to a form of "selection". Some animals die (28.6%), whereas others survive despite: i) prolonged failure to put on weight, ii) alopecia (80% loss of hair), iii) severe conjuntivitis, iv) blepharitis, v) peripheral nervous system distress. These findings underscore the importance of investigating the relation between hazardous compounds and possible potentiating factors, on the one hand, and inclusion of organs not yet recognized as targets, on the other hand, when setting tolerance limits for ambient pollution. PMID- 4023423 TI - Variability of neurotoxicity of and lack of tolerance to the anticholinesterases soman and sarin in the rat. AB - The neurotoxicity and lethality of Soman and Sarin, after single and repeated treatment at 50-60% of their LD50 doses in rats were investigated. Single treatment with Soman (100 micrograms/kg) and Sarin (120 micrograms/kg) produced severe tremors, convulsions and hypothermia, in some rats only, while the others did not show toxicity, i.e. an all or none effect. Soman and Sarin (100-120 micrograms/kg) caused, respectively, 89-93% and 26-48% inhibition of AChE at 6 hr and 56-68% and 17-39% inhibition at 24 h after single injections. Repeated treatment with Soman (90 micrograms/kg) and Sarin (100 micrograms/kg) at 4 day intervals caused variable incidences of neurotoxicity and increasing mortalities, and after ten injections the survival rates were 31 and 54%, and AChE inhibition was 86 and 75%, respectively. It is suggested, that the variable neurotoxicity of and the low tolerance to of these compounds are partly related to peripheral dispositional mechanisms. Furthermore, the profile of toxicity of these anticholinesterase agents should be differentiated from, but not generalized with, that of the other anticholinesterase organophosphates. PMID- 4023424 TI - Urinary excretion of zinc in patients with essential arterial hypertension. AB - We report the finding of an increase in urinary zinc excretion in patients suffering from essential arterial hypertension; we find no clear explanation for this phenomenon. However, it merits a more thorough study, such as a comparison of zinc metabolism as altered by the hypertensive process. Also, urinary zinc excretion before and after (6 months) Captopril administration is reported. PMID- 4023425 TI - Increase in anti-carboxylesterase action of organophosphorothioates by nicotinamide adenine dinucleotide (NAD) in vitro. AB - The purpose of the present study was to investigate the relationship between chemical structure of organophosphorus insecticides and potentiation of anti carboxylesterase (CEase) action of these insecticides by NAD in vitro (NAD effect). Experiments using with three organophosphorothioates having ethoxy group except for diazinon exhibited greater NAD-effect than those having methoxy ones such as methylparathion and fenitrothion. In contrast, none of five organophosphates tested showed NAD-effect. And, 3-acetylpyridine adenine dinucleotide (Ac-py AD) among four derivertives of NAD was also found to have NAD effect. These results suggested that P = S group in the molecule of organophosphorus insecticides was needed to occur NAD-effect. In addition, the extent of NAD-effect using acetylcholinesterase (AChE) was lesser than that of CEase, therefore, a higher susceptibility of liver microsomal CEase to organophosphorus insecticides may be explained, at least inpart, by NAD-effect. PMID- 4023427 TI - The comparative potency of phenobarbital and five 1,3-propanediol dicarbamates for hepatic cytochrome P450 induction in rats. AB - Using a reproducible screening procedure for rat liver cytochrome P450 isoenzyme induction/inhibition, five dicarbamate drugs (meprobamate, mebutamate, carisoprodol, tybamate, and W-554) were compared with sodium phenobarbital and found to be from 25 to 100 times less potent hepatic cytochrome P450 inducers than phenobarbital. PMID- 4023426 TI - Role of brain epinephrine neurons in the regulation of serum prolactin and luteinizing hormone release in female rats. AB - Administration of phenylethanolamine N-methyltransferase (PNMT) inhibitors to estrogen (EB)-plus progesterone (PG)-treated ovariectomized (OVX) female rats produced significant reductions in hypothalamic epinephrine (Epi) levels and serum luteinizing hormone (LH) levels, but no effect on serum prolactin (Prl) levels. These results suggest that brain Epi neurons may participate in the regulation of LH release but not in controlling the surge of Prl induced by EB plus PG-treatment in OVX rats. PMID- 4023428 TI - Efficacy of immunoglobulins in gram-negative infections in experimentally induced peritonitis in the rat. AB - The effect of adjuvantly administered, newly developed immunoglobulin preparations in combination with an antibiotic is investigated by means of an animal experimental model. The animal model was peritonitis which was induced by a left-open colotomy in the rat. Administration of a combination therapy of immunoglobulins and an antibiotic succeeded in reducing lethality and shock index (according to Staub [15]) significantly by up to 50% as compared to the untreated control group. Using sub-therapeutic dosage of the antibiotic (50% of the human equivalent dose) the synergistic effect of the immunoglobulins could be confirmed clearly. A single summation of the offered immunoglobulin preparations cannot achieve an improvement in the results. In the present examinations additional IgM enrichment does not result in a further improvement over the usually normal immunoglobulin levels in the preparations. PMID- 4023429 TI - Ultrastructural studies of intercalated disc separations in the rat heart during the calcium paradox. AB - The ultrastructure of intercalated disc separations were studied in isolated rat hearts subjected to 5 min of coronary perfusion with small volumes of a calcium free solution (i.e., 10.0 ml, 5.0 ml, and 2.5 ml). The same groups of hearts were studied after 15 min of calcium repletion. A semiquantitative examination shows that after calcium depletion 20%-45% of the intercalated discs (ID) were separated in the 2.5-ml group, 50%-75% in the 5.0-ml group, and 75%-90% in the 10.0-ml group. Readmission of calcium did not give any significant changes in the percentage of ID dehiscence in the two lowest volume groups, which indicates that ID separation has been irreversible during the first 15 min of calcium repletion. A semiquantitative analysis has also been performed of the percentages of severely damaged cells at each of the three volume groups after calcium repletion. It appears that in the two lowest volume groups, the percentage of widened discs tend to exceed the percentage of severely injured cells after calcium readmission. This suggests that ID separation not necessarily implies severe injuries to the implicated cells during calcium repletion. After calcium free perfusion, cellular edema, cytoplasmic disintegration, and plasmalemmal fragmentation were present in the interdigitating cellular projections of the dissociated ID. Similar injuries did also occasionally occur outside the ID, usually situated in close proximity to a capillary. PMID- 4023430 TI - Blood flow of experimental liver metastases in rat as evaluated by the locally injected 133-Xenon washout. AB - The investigations on blood flow in liver metastases are interesting from both a pathophysiological and a therapeutic point of view. Available data, however, are few and not definitive, as these studies are complex and difficult to perform. In a group of 25 Sprague-Dawley rats, in which liver metastases of Walker-256 carcinoma had been implanted, the blood flows in a metastasis and in the normal liver surrounding it were determined by means of the locally injected 133-Xenon washout. Thirteen sham-operated rats were a control group. Blood flow in the metastases was decreased as a group compared to that in the normal liver surrounding metastases and to that in liver of sham-operated rats. Small metastases showed normal or increased blood flow, large ones decreased or stagnant blood flow. Moreover, a significant inverse correlation was found between blood flow and diameter of metastasis. It is concluded that liver metastases of Walker-256 carcinoma show a decrease in blood flow which is related to the size of metastasis. PMID- 4023432 TI - Partial nephrectomy and furosemide in toxic and ischemic nonoliguric acute renal failure in rats. AB - Reduction of the renal mass causes similar tubulo-dynamic changes as furosemide, e.g., hyperperfusion of the single nephron. Therefore, the effect of 5/6 nephrectomy (NX) and furosemide (F) either alone or in combination was evaluated in nonoliguric acute renal failure, using two toxic (glycerol and HgCl2) and one ischemic model. In the HgCl2 model, NX and F alone had a protective effect on whole kidney function, e.g., the increase in serum creatinine was smaller as compared to control rats. NX plus F was followed by the lowest mortality and the smallest increase in serum creatinine. A significant increase in mercury excretion was observed following NX plus F. In the ischemic model, NX and F had no protective effect-when combined, they even enhanced renal insufficiency. The outcome of animals treated with glycerol is neither modified by F nor by NX, although both interventions induced a significant increase of glycerol excretion. It seems that the beneficial effect of 5/6 NX and F depends on the type of acute renal failure (ARF) and the models used, and that the elimination of a toxic agent is not the common pathway of protection in the HgCl2-and the glycerol induced ARF. PMID- 4023431 TI - Effects of high hepatic acetaldehyde level following simultaneous administration of ethanol and cyanamide on liver function in rats. AB - Extremely high concentrations of hepatic acetaldehyde were induced in rats by the intragastric administration of ethanol and cyanamide, an aldehyde dehydrogenase inhibitor; and these high levels were maintained for 4 weeks. Liver function tests, including mitochondrial ornithine carbamoyltransferase (OCT) and GOT activities, were within normal limits, and no increase in either hepatic triglyceride or collagen contents was observed. These results suggest that hepatotoxic effects of ethanol are not derived from the high acetaldehyde levels in the liver. PMID- 4023433 TI - Sequential changes in blood concentrations of fuels in relation to arterial blood ketone body ratio after 70% hepatectomy in rabbits. AB - The changes in arterial blood levels of glucose, free fatty acids, ketone bodies, and amino acids were investigated after 70% hepatectomy in rabbits in relation to the changes in adenylate energy charge of the remnant liver and ketone body ratio of arterial blood. Hepatic energy charge decreased to 0.767 +/- 0.008 within 24 h (p less than 0.001), and arterial blood ketone body ratio decreased to 0.415 +/- 0.041 within 12 h (p less than 0.001). Plasma free fatty acid concentrations increased to about twice the original values within 12 h (p less than 0.01), total amino acid concentrations also doubled within 24 h (p less than 0.01), and blood glucose levels decreased to below 100 mg/dl at 12 and 24 h (p less than 0.05). Afterward, at 96 h postoperatively (p.o.), blood ketone body ratio and energy charge levels were restored to near normal levels with the normalization of blood glucose, plasma free fatty acids, and plasma amino acids. These findings suggest that the decreased energy charge of the remnant liver concomitant with a fall in blood ketone body ratio may be the basis of the sequential changes in the blood concentration of fuels after massive hepatectomy. PMID- 4023434 TI - Measurement of the non-specific threshold stimulus for the bronchial tree by continuous monitoring of respiratory resistance using the oscillation method. AB - Bronchial hyperreactivity to various stimuli has been used as one of the diagnostic criteria of chronic obstructive lung diseases. We studied bronchial responsiveness to histamine in 30 patients with acute or chronic bronchitis, 28 patients with bronchial asthma and in 42 more patients with other lung diseases, using a new device--the Astograph--which yielded graphically a continuous dose response curve of the respiratory resistance by the oscillation method during the inhalation of histamine diphosphate. The results of this method were compared with the results of FEV1 and FEF25-75 before and after the challenge procedure. An increase of the respiratory resistance (Ros) during the challenge test gave an indication of a decrease of FEV1. The increase of Ros and the decrease of FEV1 and FEF25-75 were most pronounced in the asthmatics. Not in all cases was there a correlation between the increase of Ros and the decrease of FEV1, possibly due to imperfections in the design of the equipment. We believe that the Ros measurement cannot be totally exchanged for the conventional method. The use of the Astograph alone cannot be recommended because of the false-negative reactions. A combination Astograph/Floop equipment is rather expensive, but it is the most rational and ideal. The test itself does not induce bronchoconstriction and is simple and time-saving. However, this procedure is not yet advised as a diagnostic tool for a challenge test with allergens in the diagnosis of bronchial asthma. A further investigation on the validity and security of such a provocation is still needed. PMID- 4023435 TI - Inspiratory and expiratory resistive load detection in normal and asthmatic subjects. A sensory decision theory analysis. AB - The ability to detect added external inspiratory and expiratory resistive loads was studied in normal and asthmatic subjects using sensory decision theory as a psychophysical method. Performances P(A)/delta R [where P(A) represents the index of sensitivity and delta R the additional resistor] were similar in normal and asthmatic subjects, but when sensitivity was expressed in relation to airway resistance [P(A)/delta R/Raw], asthmatics showed higher inspiratory and expiratory performances than normal subjects. After bronchodilation the relative sensitivity in the asthmatic group was impaired and approached that of normal subjects. Comparing inspiratory and expiratory load detection, normal subjects showed a higher sensitivity for expiratory than for inspiratory loads. In contrast, there was no difference in the asthmatic group. The response bias remained the same across conditions. If one accepts the assumption that the variability of sensitivity presented by asthmatic and normal subjects might be related to the variable state of their pulmonary function, our results can be interpreted as demonstrating a relationship between sensitivity and pulmonary distension or airway obstruction. These results are in agreement with the hypothesis that the site of perception for respiratory load detection is the chest wall. PMID- 4023436 TI - Measurement of reversibility of airways obstruction: which parameters to use? AB - Maximum expiratory flow-volume (MEFV) curves recorded before and after salbutamol inhalation on 100 patients with various lung diseases were studied. Improvement was found to occur more frequently in MEF50, FEF25-75, FVC and MEF25, than in FEV1, FEV1/FVC%, or MTT. If improvement in only one of the first four parameters was taken as a measure of reversibility of airways obstruction, many cases showing improvement in the others were missed. Improvement in any of the last three parameters was rarely missed if improvement in any of the first four was present. It was concluded that there is no single best measurement for assessment of bronchodilator response. FVC, FEF25-75, MEF50 and MEF25 should all be measured. A flow-volume record of forced expiration from which all these measurements can be derived would therefore be preferable for this purpose to the time-volume spirometer record from which only FVC and FEF25-75 can be determined. PMID- 4023437 TI - Induction of acetylcholinesterase inhibition in the guinea pig trachea by kerosene. AB - The effect of kerosene on in vivo and in vitro tracheal acetylcholinesterase (CHE) activity of guinea pigs has been investigated. Kerosene aerosol administered to guinea pigs during 20 min at a mean concentration of 20.4 mg/l elicited immediately, 1 h and 24 h later tracheal CHE inhibition by 30, 48.8, and 32.3% of control values (p less than 0.05). Kerosene at 1% concentration inhibited significantly, after 1 h of incubation in vitro, the CHE activity by 44.9% of control values. The tracheal CHE inhibition induced by kerosene could actually increase the acetylcholine concentration acting on smooth muscle of airways, and this partially explains the respiratory symptoms which are frequently observed after kerosene intoxication. PMID- 4023438 TI - Venous crossover PO2. A reference point for assessing the physiological significance of alterations in oxyhaemoglobin equilibrium. AB - A method is described for the quantitative analysis of the physiological significance of either an increase or decrease in P50. The venous crossover PO2 (PvxO2) refers to that PO2 of the mixed venous blood on the standard oxyhaemoglobin equilibrium (OHE) curve at which the extraction of oxygen from the blood is the same for both the standard and the in vivo arterial and venous OHE conditions. A measured PvO2 which is greater than the PvxO2 indicates that the in vivo OHE conditions conferred a benefit over the standard conditions inasmuch as the same volume of oxygen was delivered to the tissues at a higher venous PO2. The method of determining the venous crossover PO2 from the measured arteriovenous difference in haemoglobin saturation of oxygen is described using a mathematical model of the oxyhaemoglobin equilibrium curve. The presence of carboxyhaemoglobin is accounted for in this analysis. Clinical examples in which the method is applied are presented. PMID- 4023440 TI - Arterial micropuncture. An advance in blood-gas analysis. AB - Worldwide, uncountable arterial macropunctures and cannulations are performed for blood-gas analysis. The associated complications are accepted as inevitable. 8,000 arterial micropunctures performed under controlled conditions show that this sampling method is not only simpler but also less traumatic and less susceptible to errors of method. As these advantages are not countered by any disadvantages, microsampling is suggested for general use. PMID- 4023439 TI - Fatal relapse in Goodpasture's syndrome 3 years after plasma exchange. AB - Since 1919 about 400 cases with Goodpasture's syndrome have been published, and since 1975 about 100 of these patients were treated with plasma exchange in addition to immunosuppression. A remission was achieved in 50% of the 100 cases, and in 7 a relapse was reported. In this paper, we are reporting a case with a fatal relapse 3 years after successful plasma exchange treatment. This patient was a smoker, she had been exposed to hydrocarbon solvents, and she had the HLA tissue antigens DR2 and MT3. Lung biopsy by fiberoptic bronchoscopy revealed linear staining of IgG at the alveolar basement membrane. During relapse pulmonary infiltrations and macrohematuria did not respond a second time to methylprednisolone pulses nor to plasma exchange treatment and the patient died of massive lung hemorrhage. PMID- 4023441 TI - Eosinophilic pleural effusion: a review of 36 cases. AB - 36 cases of eosinophilic pleural effusion (EPE) are reviewed. The etiologies were: traumatic 25%, congestive heart failure (CHF) 14%, infectious 8.5%, idiopathic 8.5% and miscellaneous 11%. 33% (12 patients) had a tumoral etiology, yet in only 1 patient could all additional etiologies for EPE be ruled out. Hence, the conclusion is that EPE is rarely caused by a tumoral etiology, and that other etiologies should be considered. The comparison of pleural fluid and peripheral blood findings disclosed no significant difference among the various subgroups. PMID- 4023442 TI - Spontaneous pneumothorax in cryptogenic fibrosing alveolitis. AB - The prevalence of spontaneous pneumothorax was studied in 82 patients with cryptogenic fibrosing alveolitis. In 46 patients the disease affected only the lung ('lone' fibrosing alveolitis); in the remaining 36 patients the interstitial lung disease was associated with several systemic diseases ('associated' fibrosing alveolitis). 3 patients with the 'lone' form had a spontaneous pneumothorax. This figure represents a prevalence of 3.6%. We did not observe this complication in any patient with the associated form. Suction drainage was ineffective in the 3 patients. One of them died as a consequence of pleural infection. In the other 2 subjects thoracotomy, resection of blebs and pleurectomy were required. PMID- 4023443 TI - Adrenal function in asthmatics treated with high-dose budesonide. AB - Plasma cortisol concentrations have been measured in 14 asthmatics previously treated with oral steroids in addition to conventional doses of beclomethasone dipropionate. Three months after switching over to budesonide in a dose of 800 micrograms twice daily, oral steroid intake has been reduced and a return of the initially depressed adrenal function has been achieved. PMID- 4023444 TI - Effect of decortication in fibrothorax on pulmonary function. AB - Pulmonary function was measured pre- and postoperatively in 11 decorticated fibrothorax patients using dynamic spirometry and radiospirometry. Total ventilatory and perfusion percentage increased significantly in the decorticated lung (p less than 0.001 and p less than 0.005, respectively). Dynamic spirometry values improved only slightly. PMID- 4023445 TI - [Detection of oxygen lung injury by NMR method]. PMID- 4023446 TI - [Quantitative assessment of pulmonary microvascular permeability]. PMID- 4023447 TI - [Perfusion of the isolated lung lobe]. PMID- 4023448 TI - [Pulmonary vascular injury induced by air embolization]. PMID- 4023449 TI - [Role of thromboxane A2 in pulmonary air embolism in conscious sheep]. PMID- 4023450 TI - [Formulas of acid-base balance]. PMID- 4023451 TI - [Study on the new index U2/AP in canine aortic root for left ventricular performance]. PMID- 4023452 TI - [Clinical significance of plasma norepinephrine and epinephrine early in the course of acute myocardial infarction]. PMID- 4023453 TI - [The quantitative evaluation of chest roentgenograms in right ventricular systolic and diastolic overload]. PMID- 4023454 TI - [Clinical and hemodynamic effects of continuous intravenous injection of isosorbide dinitrate in patients with congestive heart failure]. PMID- 4023455 TI - [Studies on unevenness of regional ventilation and volume in patients with bronchial asthma]. PMID- 4023456 TI - [Massive pulmonary embolism in a patient with Ebstein's anomaly]. PMID- 4023457 TI - [A case of mitral stenosis presenting left sided heart failure--consideration on the genesis of left ventricular dysfunction in mitral stenosis]. PMID- 4023458 TI - [Transition of effort angina to micturition angina in a female patient]. PMID- 4023459 TI - [A case of severe disopyramide poisoning, treated successfully by haemodialysis]. PMID- 4023460 TI - [Problems in the clinical use of non-steroidal antirheumatic agents]. PMID- 4023461 TI - [The long-term positive effects of educational-motivational care of patients with ankylosing spondylitis]. PMID- 4023462 TI - [Functional diagnosis of disorders of the humeroradial epicondyle]. PMID- 4023463 TI - [Socioeconomic aspects of degenerative disorders of the spine and the role of functional therapy and education in the treatment of the patients]. PMID- 4023464 TI - A consideration of the ethics of brain death--what are the ethical guidelines for physician, family and society in dealing with brain death? AB - There is at present considerable confusion with respect to ethical guidelines that should govern the behavior of society and the physician confronted by problems resulting from recent attainments of medicine and science. The use of life supporting devices raises the problem of determining when death has occurred and what is proper ethical procedure in dealing with the deficient half life caused by "Brain Death." Some guidance is obtained from a consideration of the nature of life, the nature of death, the nature of man, and the essence lost in death of man. A parallel consideration of the nature of ethics, the bases of ethics and of ethical decision can be helpful. An individual may have ideals which control behavior, even elevate ethical standards; others entertain concepts that destroy social ethics. Ethics control and direct social interactions; ethics determine the quality of social behavior--ethics are established by societies not by individuals. Numerous commissions have endeavored to define the requirements of physicians for diagnosing brain death and for appropriate subsequent actions. The rationales presented, however, are not invariably accepted by lay society. The problem is created by numerous trends. Among them are the "rightest" movement which, though possessing many virtues, has its excesses such as expressed in the "right to life movement." These have not been beneficial and have necessitated "right to death movements." Opposition is also due to the fact that society's concepts of the medical profession have changed. The practice of organ transplantation has created problems. Finally, the concept of death as other than evil is no longer generally accepted. As more biological manipulations are possible ever more difficult ethical problems will arise. It is a certainty, however, that when brain death has occurred life of man and that of the individual has ended. Although others might not agree, our ethic requires us to use life assist techniques to preserve the vegetative man, the individual who can still breathe spontaneously though lacking consciousness and behavioral ability. All the codes of medical ethics state that a physician shall not kill--this does not mean he cannot permit the terminal phases of death when the essence of human life is lost. A major question is the ethical responsibility of one society toward another. Can an affluent society squander its resources in the preservation of ineffectual life in the body after "brain death" when others are without the medical assistance which would permit total living? PMID- 4023465 TI - Effect of some environmental factors on survival of overwintering mosquitoes, Culex pipiens pallens. AB - In connection with the possible overwintering of Japanese B encephalitis virus in mosquitoes, some experiments were carried out to examine the effect of temperature, day-length and blood feeding on the survival of the overwintering population of the mosquito, Culex pipiens pallens. No significant difference was observed in the survival rate between the blood-fed and unfed groups under a higher temperature (24 degrees C) and longer day-length (L:D 14:10). Under a lower temperature (16 degrees C) and shorter day-length (L:D 10:14), blood-fed mosquitoes survived twice as long as those under a higher temperature and longer day-length condition. Based on the analysis of wing-length distribution, it was clarified that the blood-fed mosquitoes were a uniform longer-winged group and that most of the shorter-winged mosquitoes were included in the unfed group. Judging from such lower blood-feeding activity of the shorter-winged mosquitoes, their survival rate is suggested to be low during or after overwintering. PMID- 4023466 TI - The presence of macromolecular prolactin in serum of pregnant women and patients with pituitary adenoma. AB - The heterogeneity of immunoreactive Prolactin (IR-PRL) in serum of pregnant women and patients with pituitary adenoma were studied by Sephadex G-100 gel chromatography. The major IR-PRL peaks in serum of pregnant women were eluted at the position corresponding to that of 125I-PRL and the small amount of IR-PRL peaks were eluted near the void volume (peak 1) and between the void volume and 125I-PRL (peak 2). On the other hand, the proportion of peak 1 and peak 2 to total immunoreactivity was significantly increased in serum of patients with pituitary adenoma compared to those in serum of pregnant women. The rechromatographic studies under conditions of protein denaturation and sulfide cleavage on Sepharose CL-6B column revealed that the peak 1 of the pregnant women and patients with pituitary adenoma were eluted at the position between 125I-AFP and ovalbumine and the molecular weight was estimated to be about 54,000. This macromolecular PRL was also bound specifically to Sepharose coupled with anti PRL, indicating that this macromolecule contained a sequence of PRL in its structure. PMID- 4023467 TI - [Mammography in diagnosis of breast cancer]. AB - Radiographic features of 50 breast cancers were evaluated in comparison with 83 benign lesions and the diagnostic accuracy is discussed. Most of the usual primary and secondary findings of cancer such as spicula formation, microcalcifications, skin, thickening and nipple retraction were present in these 50 cancer lesions and all of them were recognized in the benign lesions as well, although less frequently. Because breast parenchyma was dense in 81% of the cases evaluated, and mostly due to moderate to severe dysplasia, the diagnosis of the breast lesions was difficult. Therefore, we must be cautious in calling a lesion benign. The radiographic detectability of cancer was 94%, and the diagnostic accuracy was 72%, which are comparable to the results reported from other places. PMID- 4023468 TI - [A personal sampling and an area sampling--exposure concentration and environmental concentration]. AB - Two methods for the evaluation of air contaminant in a work environment are personal sampling to measure the exposure concentration for the evaluation of the exposure level to workers and area sampling that measures the environmental concentration for the evaluation of the clean level in the work environment. The aim of these samplings is different but they are used to measure the concentration in the same work environment. It is important to understand the difference between the exposure concentration and the environmental one in the same work environment. In this report, the relationship between the exposure concentration and the environmental one is investigated by using previous reported data. The difference between the exposure concentration and the environmental one is very large for all data, but the exposure concentrations agree well with the environmental ones when the both concentrations were measured by the same apparatus in some work environments. PMID- 4023469 TI - [Health check by CMI (Cornell Medical Index) on radiation workers in a nuclear energy plant]. AB - In the nuclear energy industry, plants are located far from urban areas and the working environments are generally separate from each other for radiation protection purposes. A health check on radiation workers in the nuclear energy industry was carried out using the Cornell Medical Index questionnaire. As a control study, radiation and non-radiation workers in the other working fields were investigated in the same manner. The results showed that the health status of radiation workers in the nuclear energy industry is similar to that of the workers in other working fields. PMID- 4023470 TI - [A case of spindle cell carcinoma of the breast]. AB - A forty-year-old woman noticed a mass in her right breast. In April, 1984, a radical mastectomy was performed and the specimen was subjected to histopathological and ultrastructural study. The well-localized tumor revealed atypical spindle cell nests in the desmoplastic stroma. Based upon a squamous differentiation of the cancer cell nests, the tumor was diagnosed as spindle cell carcinoma. The histogenesis and prognosis of this rare tumor are discussed and the myoepithelial origin is suggested. PMID- 4023471 TI - [A case of precancerous hair follicle tumor on the large pudendal lip]. AB - A case of precancerous hair follicle tumor of a 60-year-old woman is reported. The tumor was detected in the large pudendal lip of an ATL-suspected patient. Microscopic findings showed that the tumor was a hair follicle tumor of low malignancy, such as a "malignant trichilemmoma", or "follicular Bowen's disease". Histogenesis and pathogenesis of this tumor are discussed including the relationships to ATL and "Trichilemmal horn". PMID- 4023472 TI - The 2 x 2 factorial design: its application to a randomized trial of aspirin and carotene in U.S. physicians. AB - The 2 x 2 factorial design calls for randomizing each participant to treatment A or B to address one question and further assignment at random within each group to treatment C or D to examine a second issue, permitting the simultaneous test of two different hypotheses. This design can increase the efficiency of large scale clinical trials. The Physicians' Health Study, a randomized trial of aspirin and beta-carotene among U.S. physicians, illustrates some features and potential problems in the design and analysis of a factorial trial. The most common concern, interaction between treatments, is generally an advantage rather than a limitation of this design. Although such interactions are relatively uncommon, this design provides a means to measure an effect which otherwise might not be apparent. If the interaction is sufficiently severe, however, then loss of power is possible. PMID- 4023473 TI - Power, sample size and smallest detectable effect determination for multivariate studies. AB - This paper discusses some general methods for determining approximate power, sample size, and smallest detectable effect for studies of multiple risk factors. These methods are based on standard large-sample formulae for determining the power of chi-square tests, and emphasis is given to determinations for Pearson chi 2 tests in multiway contingency tables. The methods are illustrated in application to the design of a clinical trial of the preventive effect of alpha tocopherol, ascorbic acid and beta-carotene on colon polyp recurrence, and a case control study of the joint effect of smoking and asbestos exposure on lung cancer incidence. PMID- 4023474 TI - Models and the use of signed rank tests. AB - Rank tests are often used to analyse medical and biological data. The lack of invariance of the paired sample Wilcoxon signed rank test with respect to transformation of observations, and the choice of an appropriate rank test in the case of the two way analysis of variance random effects model, are discussed in the context of two medical examples. PMID- 4023475 TI - Comparison of ascertainment-bias correction schemes for pedigrees ascertained through multiple probands. AB - Assessing the genetic causation of a disease, which is of prime importance in medical genetics, is usually done by analysing pedigree data. When gathering such data, it is often more practical to adopt a non-random sampling strategy. However, unless suitable corrections for non-random sampling are made at the time of data analysis, inferences may be grossly affected. For pedigree data ascertained through multiple probands, various correction schemes have been suggested, although the efficiencies of these schemes are unknown. This paper compares such schemes, using Monte Carlo simulation techniques, under a simple genetic model, for pedigrees of fixed sizes and structures and for probands of two types of relationship--parent-offspring, and a pair of siblings. It is found that gene frequencies are grossly overestimated and the penetrance value of heterozygotes slightly underestimated whether or not any correction for non random sampling of pedigrees is made. Knowledge of the population value of the gene frequency improves the estimate of the penetrance parameter. PMID- 4023476 TI - The use of logit models to investigate social and biological factors in infant mortality. I: Methodology. AB - Infant mortality data for England and Wales, cross classified by mother's age, parity and social class, have been published on two occasions, the first giving the relevant data for 1949/50, the second for 1975, some 25 years later. Published analyses of these separate data sets have been based on graphical and tabular methods. This paper describes the statistical methodology appropriate to the use of logit models to investigate these data sets and shows how such models may be used to supplement the more informal approach. The stillbirth data for 1975 are used for illustration. Paper II, which follows, explores the stillbirth data in greater detail, with emphasis on the changes between 1949/50 and 1975. Subsequent papers describe neonatal and post-neonatal deaths using the same framework. A final paper summarizes the overall changes in infant mortality by means of a multilogit model. PMID- 4023477 TI - The use of logit models to investigate social and biological factors in infant mortality. II: Stillbirths. AB - Infant mortality data for England and Wales cross-classified by mother's age, parity and social class have only been published for 1949/50 and 1975. Appropriate statistical methodology for the analysis of such data has been described in Paper I, which used the 1975 stillbirth data for illustration. This paper examines the stillbirth data from both years by formally incorporating the year of data collection into the statistical model, enabling changes in the age, parity and social class effects with time to be investigated. Despite a marked reduction in stillbirth mortality from 21.1 to 10.1 per thousand over the period, the relative contribution of social class has increased. In particular there has been a relative increase in risk for mothers in the lower social classes. By contrast the effects of age and parity, although remaining important, have diminished over the period. PMID- 4023478 TI - Empirical Bayes estimation of cancer mortality rates. AB - Mortality rates for specific cancer types and age-sex groups computed for large numbers of cities typically show extreme fluctuation. This is primarily due to the rare occurrence of specific cancer deaths in most of the small and moderate size cities during a fixed time period. Assuming a Poisson death process, we use an empirical Bayes method to obtain adjusted rates that are more stable for comparison of cities and prediction of future mortality. We have chosen stomach and bladder cancers in Missouri cities to illustrate the problems, techniques and results. PMID- 4023479 TI - Comparative analysis of two rates. AB - In this paper, we examine comparative analysis of rates with a view to each of the usual comparative parameters-rate difference (RD), rate ratio (RR) and odds ratio (OR)-and with particular reference to first principles. For RD and RR we show the prevailing statistical practices to be rather poor. We stress the need for restricted estimation of variance in the chi-square function underlying interval estimation (and also point estimation and hypothesis testing). For RR analysis we propose a chi-square formulation analogous to that for RD and, thus, one which obviates the present practice of log transformation and its associated use of Taylor series approximation of the variance. As for OR analysis, we emphasize that the chi-square function, introduced by Cornfield for unstratified data, and extended by Gart to the case of stratified analysis, is based on the efficient score and thus embodies its optimality properties. We provide simulation results to evince the better performance of the proposed (parameter constrained) procedures over the traditional ones. PMID- 4023480 TI - On the use of the logistic model in prospective studies. AB - We describe the usual statistical concepts and consequent appropriate simulations of a prospective study for the simple case of a single risk variable and an assumed logistic model. We examine the simulations of Lilienfeld and Pyne, and show that they are seriously flawed. Contrary to those authors' claims, the estimates of parameters by the Walker-Duncan technique are both accurate and reliable. PMID- 4023482 TI - Bias correction in maximum likelihood logistic regression. PMID- 4023481 TI - The logistic analysis of epidemiologic prospective studies: investigation by simulation. PMID- 4023483 TI - Approaches to sample size estimation in the design of clinical trials--a review. PMID- 4023484 TI - [A case of polymer fever]. PMID- 4023485 TI - [A case of immune deficiency in a Zaire infant: AIDS?]. PMID- 4023486 TI - [Hyperandrogenism and hyperprolactinemia, causes of female infertility. Current treatment]. PMID- 4023487 TI - [Value of microsurgery in the treatment of infertility of tubal origin]. PMID- 4023488 TI - [In vitro fertilization and embryo transfer in the treatment of infertility]. PMID- 4023489 TI - [Treatment of male infertility]. PMID- 4023490 TI - [A mediastinal seminoma]. PMID- 4023491 TI - [Screening for recto-colic neoplasms by the detection of occult blood in the stool: a study in the hospital milieu]. PMID- 4023492 TI - [Pigmented villonodular synovitis of the knee. A propos of 2 cases]. PMID- 4023493 TI - [Etiopathogenesis of insulin-dependent diabetes]. PMID- 4023494 TI - [Acute mesenteric ischemia]. PMID- 4023495 TI - [New local treatment of ulcers of the lower limb]. PMID- 4023497 TI - [Management of alcoholics]. PMID- 4023496 TI - [The generalist and fatigue]. PMID- 4023498 TI - [Drug update]. PMID- 4023499 TI - [The significance of genetic factors in epilepsies]. PMID- 4023500 TI - [Reflex epilepsies]. PMID- 4023501 TI - [Risk of malformation in anticonvulsant therapy in pregnancy]. PMID- 4023502 TI - [Hyperventilation syndrome]. PMID- 4023503 TI - [Clear cell adenocarcinoma of the vagina and cervix: diagnosis and etiology as seen in a few cases without diethylstilbestrol anamnesis]. PMID- 4023504 TI - [Ambulatory plastic surgery]. PMID- 4023505 TI - [Dangerous waterborne viruses in natural waters?]. PMID- 4023506 TI - [Thoracic pain, dyspnea]. PMID- 4023507 TI - [The hypercalcemia syndrome]. PMID- 4023508 TI - [Pulmonary embolism]. PMID- 4023509 TI - [Spinal compression]. PMID- 4023510 TI - [Necrotizing fasciitis]. PMID- 4023511 TI - [Pericardial tamponade]. PMID- 4023512 TI - [Prevention of hepatitis B: questions and answers]. PMID- 4023513 TI - [Psychological adjustment in the physician-patient relationship]. PMID- 4023514 TI - [Intramuscular lipoma of the thigh]. PMID- 4023515 TI - [Cough, hemoptysis, thoracic pain]. PMID- 4023516 TI - [Childhood hearing loss and its early diagnosis]. PMID- 4023517 TI - [The involution of cerebral dominance]. PMID- 4023518 TI - [Reflections on stuttering and the psychotherapeutic treatment of stutterers]. PMID- 4023519 TI - [Payments and interventions by the federal disability insurance in cases of language disorders in children of preschool age]. PMID- 4023520 TI - [The child psychiatrist faced with the description of language phenomena and their interpretation]. PMID- 4023521 TI - [Examination, diagnosis and treatment of functional language disorders]. PMID- 4023522 TI - [Early guidance of deaf children and their parents]. PMID- 4023523 TI - [Chronic meningoencephalitis with progressive internal hydrocephalus]. PMID- 4023524 TI - [Evolution of children hospitalized at the Bercail for a pathologic behavioral structure, a consequence of abandonment or early affective deprivation]. PMID- 4023525 TI - [Peripheral arterial insufficiency in athletes]. PMID- 4023526 TI - Bacteremia caused by Aeromonas species in hospitalized cancer patients. AB - Bacteremia caused by Aeromonas species occurred in 24 hospitalized patients in a cancer institute during a 13-year period. All but one of these patients had a malignancy (88% had leukemia), and most were receiving chemotherapy for cancer. There was a striking numerical predominance of male patients (82%). Unlike some previously described patients with infections due to this organism, none of these 24 patients had recently been exposed to fresh or salt water or to fish. The source of the infecting organism was thought to be endogenous--i.e., from patients' own gastrointestinal tracts. The clinical presentation of sepsis caused by this organism was nonspecific, except that ecthyma gangrenosum occurred in several patients. The overall mortality rate was 28%. The combination of an aminoglycoside and a cephalosporin is appropriate therapy for bacteremia caused by Aeromonas species. PMID- 4023527 TI - The use of antimicrobial agents for noninfectious diseases. AB - Antimicrobial agents are used in the treatment of a variety of noninfectious diseases. Therapeutic action may be directed against the host immune system as well as against the microbe. Some actions conventionally classified as toxic may be therapeutically or diagnostically desirable under unusual clinical circumstances. Antibiotics are used for both their antimicrobial and antiinflammatory properties to treat several dermatologic and immune-mediated diseases. Tetracycline fluorescence indicates necrotic or malignant tissue and the depth of dermal burns. Tetracycline's affinity for new bone tissue formation has applications in both research and diagnostic assessments. Radiolabeled tetracycline can act as an imaging agent for the gall bladder and kidney. The sulfonamides and sulfones, chloramphenicol, metronidazole, and some aminoglycosides also have been demonstrated to have unusual therapeutic and diagnostic efficacy, albeit by mechanisms not always understood. Although not all reported unconventional applications of antimicrobial agents remain in use, sharpening awareness of their multifaceted actions should encourage broader understanding of all agents traditionally confined to specific uses. PMID- 4023528 TI - The phagocytic cell: summary. PMID- 4023529 TI - Regulatory mechanisms of a chemoattractant receptor on human polymorphonuclear leukocytes. AB - The oligopeptide chemotactic factor receptor in leukocyte membranes exists in two affinity states that are in part interconvertible. Convertibility is regulated by guanine nucleotides, which suggests that a nucleotide regulatory unit allosterically modifies receptor affinity and participates in its transduction mechanisms. Approximately one-third of the high-affinity receptors in polymorphonuclear leukocyte (PMN) membranes are not subject to guanine nucleotide regulation. This fraction can be increased by agonist preincubation and could represent an intermediate form of the receptor prior to signal transduction and/or internalization. Pharmacologic manipulation of viable PMNs demonstrates that the affinity and functional activity of the chemoattractant receptor can be altered divergently by aliphatic alcohols and polyene antibiotics. The alcohols raise the receptors' affinity, enhance chemotaxis, but markedly depress chemoattractant-induced secretory mechanisms. In contrast, polyene antibiotics lower the receptors' affinity, depress chemotaxis, but enhance specific granule secretion. Thus, a relationship exists between the chemoattractant receptors' affinity and their ability to transduce signals for either chemotaxis or secretion. PMID- 4023530 TI - Cellular strategies in receptor-mediated phagocytosis. AB - Two strategies by which mononuclear phagocytes restrict and localize their microbicidal capacities are reviewed. The first concerns the ability of macrophages to seal off a closed compartment between themselves and opsonized targets. This compartment may be used to contain, concentrate, and protect toxic substances secreted by the phagocyte. The second concerns the ability of macrophages to regulate the phagocytosis-promoting capacity of their C3 receptors. C3 receptors are maintained in an inactive state, but they can be readily activated at sites of infection in such a way that they promote vigorous phagocytosis. PMID- 4023531 TI - [Bronchoalveolar lavage data in localized pulmonary tuberculosis]. AB - Twenty-two patients with radiologically localised pulmonary tuberculosis underwent one or more broncho-alveolar lavages: 10 patients had a single lavage in the disease area, 11 had two lavages (1 in a healthy zone and 1 in the affected zone) and 1 patient had a triple lavage. The laboratory analysis of the fluid revealed that the tuberculosis was accompanied by an elevation of the various proteins assayed and by an alteration in the cytology (lymphocytosis, neutrophilia or mixed) in the radiologically involved zone. In contrast,the healthy zone revealed normal values except in 2 cases which presented a lymphocytosis. The type of cytological abnormality does not appear to have any prognostic value, but is probably related to different pathophysiological mechanisms. PMID- 4023532 TI - [Legionnaires' disease: 21 cases observed over 2.5 years in a Parisian respiratory intensive care unit]. AB - The incidence of Legionnaire's disease is probably underestimated in France. Its clinical presentation is very suggestive, especially after the failure of a 48 hour therapeutic trial of beta-lactams, when a pneumococcal infection is initially suspected. This one sign is sufficient to orient the diagnostic survey and constitutes an indication for a therapeutic trial of macrolides for at least 72 hours. In fact, the delay in the diagnosis appears to be the determinant factor in the fatal outcome of the disease. PMID- 4023533 TI - [Steady-state carbon monoxide transfer during progressive muscular exercise in patients. Relation to PaO2. Value of specific VCO]. AB - During muscular exercise, the alveolo-capillary gas exchange reaches its optimal capacity, but taking blood for arterial blood gases is associated with certain risks and the classical criteria of CO transfer in the steady state are difficult to interpret as they are influenced by age, sex, ventilatory regime. The "specific" CO uptake (VCO Sp) does not correspond to these criteria (6). When related to the ERCO2, it allows the DuCO to be determined (4). It has the same value at the 3rd minute and at the 10th minute of constant exercise (5). Like TCO, it is correlated with the PaO2 during effort (5). In this study, a triangular exercise was performed by men aged between 45 add 55 years, smokers and former smokers, classified into 4 A: 12 healthy subjects; B: 56 cases of chronic respiratory disease; C: 9 cases of chronic obstructive airways disease (COAD); D: 12 cases of diffuse pulmonary fibrosis (DPF). Groups C and D were derived from group B. The VCO SP, TCO and DuCO were measured at each plateau of the triangular exercise. In the patients, the PaO2 was measured at the same time as the FF (CO, CO2). In the last phase of exercise (Ex. Max.): VCO Sp was more frequently altered at rest and more strongly correlated to TCO; TCO/V had the same significance as DuCO. The results of TCO, VCO Sp and DuCO were compared between groups A, C and D.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4023534 TI - [Value of a brief ergometric test in the functional evaluation of chronic bronchopneumopathy]. AB - The purpose of this work was to study the usefulness of short muscular exercise as part of standard respiratory function testing. A group of 19 patients with chronic bronchitis performed moderate load exercise (30 to 60 watts) on a cycle ergometer for 10 mn. Blood gases and acid-base balance were measured at rest, at the 2nd and the 10th mn of pedaling. In spite of highly significant relationships between resting values (blood gases, spirometry) and exercise data (blood gases), the scattering of the results precludes predicting the latter from the former. In contrast, the comparison between each of the two exercise results (2nd and 10th mn) shows not only a highly significant correlation but also a standard deviation to the regression lines which is objectively diminished. Thus, muscular exercise seems to give specific information that could be a useful component of respiratory function testing. Further, blood gas results obtained at the 2nd mn of muscular exercise suffice, thus obviating the need for a longer exercise programme that might be badly tolerated by patients. PMID- 4023535 TI - [Tracheobronchial clearance in the hypersecreting asthmatic patient]. AB - Tracheo-bronchial clearance in the hyper-secreting asthmatic patient was studied by observing the elimination over a period of time of a tracer placed on the bronchial wall over time. The authors describe the method used. The analysis of the results enables two purification processes to be distinguished: muco-ciliary activity and cough. The reliability of the method enabled comparison of the results obtained in 7 healthy subjects and 11 hyper-secreting asthmatics. In the healthy subjects, clearance is carried out by the muco-ciliary activity. In the asthmatics, global clearance is normal, but the cough plays an essential role as the muco-ciliary activity is decreased. The question then arises as to whether the decreased muco-ciliary activity in asthmatic patients is due to failure of the bronchial cilia or to the mucus. PMID- 4023536 TI - [Paracentric inversion: a study of 2 new cases]. AB - Two new cases of paracentric inversion are reported. One involved the short arm of chromosome 1 and affected two generations and the other involved the long arm of chromosome 5 and was described in 5 generations. The relationships between paracentric inversions and reproductive problems are discussed in the light of the literature. PMID- 4023537 TI - [Pregnancy and labor in Gabonese adolescent girls. A study of 97 cases]. AB - The authors report a study of pregnancy and delivery in adolescent girls, based on a series of 97 cases of young Gabonese women. The study examined this subject from two points of view: obstetrical, in which the results were essentially identical to those of other studies and in other countries, and psycho-socio economic, which revealed the feelings of shame and the problems associated with caring for the newborn infant. PMID- 4023538 TI - [Treatment of stage I and II uterine cervix cancer. Round table]. PMID- 4023539 TI - [Therapeutic trial of the combination promestriene-chlorquinaldol in the treatment of vaginitis]. PMID- 4023540 TI - [The rape of a spouse and its medicolegal implications]. PMID- 4023541 TI - [Radiation and surgical treatment of cancer of the cervix uteri in proximal stages I and II]. AB - No results from therapeutic trials describing the best therapeutic procedure for cervical carcinoma in stages I and IIa are available. Analysis of a series of 242 cases of cervical carcinoma in stages I and IIa, from 1975 to 1980, treated with radical surgery and radiation therapy, yields a therapeutic approach that envisions the most reliable evaluation of subclinical extension, cure of cervical tumor and prevention of pelvic or extra-pelvic metastases with a minimum of post radiation problems. The choice of combination surgery and radiation therapy is primarily determined by staging and the volume of the central pelvic tumor. For stages I and IIb (upper third of vagina involved) with central pelvic tumor less than 4 cm in diameter, the usual procedure is recommended i.e. radium application, total hysterectomy with pelvic lymphadenectomy followed by external irradiation of pelvic lymphatics in cases with lymphadenopathy. For stages IIb (obvious parametrial involvement) and for stages I or II with central pelvic tumor between 4 and 6 cm in diameter: total dose external and internal pelvic radiation therapy followed by total hysterectomy without pelvic lymphadenectomy but with exploration of obturator, hypogastric, external iliac, common iliac, and aortic nodes. For the rare supravaginal central pelvic tumors greater than 6 cm in diameter, the risk of clinical evaluative error and incomplete sterility by irradiation alone, warrants first an explorative laparotomy using Wertheim's procedure, then pelvic lymphadenectomy and exploration of pelvic and aortic lymph nodes. PMID- 4023542 TI - [Epidemiologic factors in ovarian cancer]. AB - Ovarian carcinoma is the most severe gynecological cancer with an overall incidence of 12 per 1000 Americans or Europeans developing it over 40 years of age. Only 3 of the 12 cases will receive efficient care because the diagnosis will be made too late. This study reveals the principal risk factors i.e. upper socioeconomic echelon, ovarian function uninterrupted by a pregnancy or usage of oral contraceptives, anamnestic evidence of ovarian carcinoma in the family, some hereditary disorders, external insults (talcum powder). The synthesis of these various risk factors permits a comprehensive review of the hypotheses of pathogenesis concerning recurrence of tumors. But corollary epidemiologic studies are still needed to try to define better the high risk groups whose follow-up systematic detection and testing is a priority. PMID- 4023543 TI - [Electrophoretic control of serum proteins in donors designated for plasmapheresis. Initial evaluation of the analysis of 3500 donors]. AB - Total serum proteins were evaluated and serum protein electrophoresis performed on 3 500 blood donors after plasmapheresis. The results were standard for total serum proteins, serum albumin and immunoglobulin in 98% of the donors, whereas monoclonal immunoglobulin, immunodeficiencies or polyclonal hypergammaglobulinemia were detected in 2% of them. The frequency of monoclonal components is roughly 0.3%, corresponding to the frequency observed in normal adults of 40 to 60 years old. Donors found with monoclonal immunoglobulins or immunodeficiency should not be considered as eligible for blood donation. PMID- 4023544 TI - [Cold lymphocytotoxins in schistosomiasis mansoni]. AB - The serum of 134 patients infected with Schistosoma mansoni, including both acute and chronic forms of the disease, were tested for the presence of cold lymphocytotoxins. These were found in 4.5% of acute forms of the disease, in 88.4% of chronic infections and in only 9.8% of the uninfected control group (blood donors). An analysis of the results suggests a probable role for cold lymphocytotoxins in the immune response of the different phases of human schistosomiasis. PMID- 4023545 TI - [Idiotypic regulation of the immune response]. PMID- 4023546 TI - [The micro-computer card. Possible applications to transfusion from A to Z]. AB - Following characteristics of micro-computer cards: inaccessibility to selected secret information; strong resistance to aggressive external agents; impossibility of altering stored data without destroying it; instant reading and reproduction by authorized services; make them a perfect material for building up individual records of civil and biological data. Their application to blood transfusion allows increased safety not only for blood donation registrations, but above all when transfusion takes place; they may also be used as credit cards for health expenditures. They consequently serve as real LIFE cards. PMID- 4023547 TI - [Case of Listeria monocytogenes meningitis with a benign course in a healthy adult]. AB - We herein describe the case of Lysteria monocytogenes meningitis. The isolation and identification of the bacteria causing the infection ollowed the antibiotic treatment followed by complete remission. Our data also support the hypothesis on intense immunological response producing a favourable evolution of the disease. PMID- 4023548 TI - [Giant carotid-cavernous aneurysm treated by balloon catheter]. AB - The AA. report the case of a giant carotid cavernous aneurysm; clinical onset was a VI cranial nerve paralysis, and diagnosis was based upon CT and angiographic findings. They describe balloon catheter technique used to exclude aneurysm, followed by carotid ligature. They eventually emphasize radiologic and neurophysiologic studies, and clinical follow up months later. PMID- 4023549 TI - [Aneurysm of the anterior inferior cerebellar artery (AICA). 18th case in the literature]. AB - The AA. report the case of an anterior inferior cerebellar artery aneurysm (XVIIIth in world literature). Reviewing literature on the subject, they recall anatomical and clinical variations of AICA aneurysms, and report surgical techniques usually employed. PMID- 4023550 TI - [Retrobulbar optic neuritis as an initial symptom of multiple sclerosis. Results of a prospective study]. AB - 40 patients with idiopathic optic neuritis (ON) between 1st January 1967 and 31st December 1977 have been checked again from oculistic and neurological point of view between 1st January and 31st March 1983. 10 of 40 examined patients (25%) are found suffering from multiple sclerosis (MS) at the time of check up. Our research points out that idiopathic ON evolutive risk towards MS is greater in females, in people between 20 and 40 years old, in people with one or more relapses as well as in people with neurological microsymptoms at the time of ON. PMID- 4023551 TI - Vertical distribution of flying black-flies (Diptera: Simuliidae) in Central Nigeria. AB - Flying black-flies were collected using an array of 4 nets mounted on a vehicle at heights between 0.15 and 3.0 m above the ground. The vertical distribution differed amongst the 8 most abundant species, but within a particular species such as S. squamosum, there was no significant difference in the vertical distribution of the males and females, nor between females of different physiological conditions. This infers that the height of the trap on the vehicle will not normally be a source of bias during population studies. However, there was some evidence of circadian changes in the vertical distribution; during the afternoon, black-flies of all species flew higher compared with in the evening. PMID- 4023552 TI - Study on the activity of antiparasitic agents against Onchocerca lienalis third stage larvae in vitro. AB - The in vitro drug response of third stage larvae of the cattle filarial worm Onchocerca lienalis has been studied. Larvae were maintained in Minimum Essential Eagles medium supplemented with 10% inactivated foetal calf serum and exposed to the following drugs: Mel W, caparsolate sodium, suramin, ivermectin, flubendazole, levamisole and amoscanate plus 3 novel melaminylthioarsenites. Antiparasitic activity of these compounds has been assessed on their killing effects and their ability to totally inhibit the moult from the third to the fourth stage. Unfortunately, moulting occurred at a low rate in the culture system used and was not suitable as a quantitative parameter for describing drug activity. However, the results indicated that if the rate of ecdysis could be increased by improving the culture conditions, moulting could be used in this manner since exsheathment has inhibited by certain compounds at concentrations where killing effects were less than 50%. Of the compounds evaluated ivermectin demonstrated good activity, totally preventing ecdysis at 0.001 microgram/ml. The drug assay system used in this study may offer a starting point for the eventual development of a meaningful and specific in vitro screen for new anti-Onchocerca agents. PMID- 4023553 TI - Development of infective larvae of Onchocerca volvulus in diffusion chambers implanted into Mastomys natalensis. AB - Diffusion chambers containing vector-derived infective larvae of O. volvulus were implanted into male Mastomys natalensis and removed after periods up to 100 days. Nearly all chambers contained motile living parasites. After two weeks lengths and diameters of the larvae had increased significantly and after 100 days one juvenile worm showed well developed papillae at the posterior end. PMID- 4023554 TI - Studies on a focus of yaws in Ubangi, Zaire. AB - Yaws (buba, Frambosie, pian), a non-venereal treponematosis of skin and bones is a tropical disease that affects primarily children. Eradication programs launched between 1950 und 1970 reduced the incidence substantially; resurgences, however, have been reported from several countries. We have studied a geographically isolated focus of yaws in the Ubangi area of northwestern Zaire. In survey I, in 1981, of the 4.407 participants from 11 villages, 348 (7.9%) had active lesions of yaws. All patients and their contacts were treated immediately with benzathine penicillin G. In survey II, in 1982, in 6 of the previously studied villages, of 5,390 participants, 136 (2.5%) had active lesions of yaws. In 1981, the predominance of primary lesions (86%) and high numbers of patients in all age groups, with the highest prevalence (23.4%) in children 10-14 years of age, suggest that yaws recently recurred at this focus. In 1982, only 25.7% of the lesions were primary and the highest prevalence (6.5%) had shifted to the younger age group of 5-10 years-old. In survey I more males (63%) were infected in the age group 0-24 years, and more females (89%) in those over 40 years. In survey II, more males (61.3%) were infected in the age group 0-14 years, and only females (100%) in the age groups 25 years and older. Seventy-one percent (1981) and 86% (1982) of the initial lesions were on the lower limbs. Participation of the population in survey I was 41.7% and was greatest (62%) in the locality where there was a newly established dispensary. In survey II, participation rose to 73.8%. Areas adjacent to the focus of yaws with longstanding dispensaries were free of yaws.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4023555 TI - Sleeping sickness in Busoga, Uganda, 1976-1983. AB - Between 1976 and 1983 in the Busoga Region in Uganda 10,414 male and 9,560 female patients were detected with trypanosomiasis. Prior to the onset of the epidemic, Glossina f. fuscipes, the sole vector, had broken through the tsetse control barrier and had spread to cover most of the region. The fly was further observed to be resting in Lantana plants and coffee and banana plantations which are widespread in the area. A close and regular contact was thus established between man and fly. It was observed that the young and engergetic persons first became infected, but as the epidemic unfolded the older age-groups bore the brunt. The infection was also seen in all other age-groups indicating the closeness of contact between the fly and the local population. PMID- 4023556 TI - Trypanosomal cardiac valvulitis in vervet monkeys. AB - Quarantined vervet monkeys (Cercopithecus aethiops) were infected with Trypanosoma brucei (10(4) parasites/animal) in a tsetse free area. Thirteen monkeys (11 infected with T.b. rhodesiense and 2 with T.b. brucei) were studied. Animals became parasitaemic within one week after infection. The infection time lasted between 21 and 129 days; in 8 monkeys it was between 50 and 70 days. Macroscopically massive pericarditis was observed in one, pericardial effusion in one, small apical aneurysms in three. Microscopically all had pancarditis of moderate to marked degree including all 4 chambers, the apices and the valvular appendages. Trypanosomes and inflammatory cells were found in the interstitium of the 3 cardiac layers. Lymphatic drainage of trypanosomes and inflammatory cells was seen in all hearts, the lymphatic vessels showing signs of stasis. By light microscopy trypanosomes and inflammatory cells were also shown to occur in all four types of heart valves implicating diffuse valvulitis. In two instances electron microscopy confirmed the intact presence of the trypanosomes clustering in great numbers in the pars elastica of the valves. In the collagenous part, some intact single trypanosomes were seen between collagen fibres. No amastigotes were observed. These results point to select sites in organ topography which in turn may be relevant to active disease, chemotherapy and healing. The possibility of hiding places within the heart - protecting trypanosomes from the host defense and/or chemotherapeutic agents - ought to be considered. PMID- 4023557 TI - Human fascioliasis in Cajamarca/Peru. I. Diagnostic methods and treatment with praziquantel. AB - In a prospective study 34 Peruvian fascioliasis patients were followed up for three months after treatment with praziquantel. The rapid sedimentation of faeces was demonstrated to be the most appropriate parasitological technique for the diagnosis of Fasciola hepatica infections in man compared to the MIF concentration or the examination of duodenal fluid by Enterotest. After therapy with different doses of praziquantel only 21% of the patients stopped to excrete worm eggs although 17 patients had been treated repeatedly. During the period of observation all patients presented a decreasing number of symptoms. It is concluded that praziquantel is not very active against F. hepatica in man. PMID- 4023558 TI - Human fascioliasis in Cajamarca/Peru. II. Humoral antibody response and antigenaemia. AB - Four immunoassays (IgG ELISA, indirect haemagglutination = IHA, IgM ELISA and antigen ELISA) for determination of humoral antibody and of circulating antigen, respectively, were applied to sera of 45 Peruvian fascioliasis patients who were identified by demonstration of Fasciola eggs in faeces. All of the sera were reactive by at least one of the assays. Sensitivity rates were 0.98 for IgG ELISA, 0.56 for IHA, 0.51 for IgM ELISA and 0.20 for antigen ELISA. Among those 34 patients who were followed up after praziquantel therapy there was a different pattern of immunoassay results between patients who stopped excreting eggs after therapy and those who continued to pass eggs. Cure was indicated by disappearance of both IgM antibody and antigen levels during three months after treatment, whereas persistence of infection corresponded to new or re-occurrence of IgM antibody and/or circulating antigen during the period of observation. Since there was no apparent relation of immunoassay results to therapy, it is presumed that the Peruvian patients did not respond to praziquantel at all. PMID- 4023559 TI - The pathology of the small intestine in human schistosomiasis mansoni in the Sudan. AB - Peroral small intestinal biopsies were obtained from 17 patients with Schistosoma mansoni infection and 13 control subjects. There was no difference between the dissecting microscopic appearances of patients and controls. The histological sections of patients showed significant shortening and broadening of villi compared to controls. There was no significant difference in the cellularity of the Lamina propria between patients and controls except that patients had significantly more eosinophils. The biopsies from the control subjects showed appearances of tropical enteropathy. PMID- 4023560 TI - Identification of adults of the Simulium damnosum complex using hydrocarbon analysis. AB - Using advanced gas liquid chromatography in association with multivariate statistical analysis, a study of four members of the S. damnosum complex - S. sirbanum, S. damnosum s.str., S. yahense and S. sanctipauli, revealed that both adult male and female flies could be distinguished by quantitative analysis of the cuticular hydrocarbon peaks. Adult flies were obtained from sites which were known to contain a very high proportion of pure cytospecies. The females of the complex were more readily separated from each other than were the males. On the basis of preliminary results, the technique provides for the first time, a reliable method for distinguishing S. sirbanum and S. damnosum s.str., the most important vectors of onchocerciasis in the savanna areas of West Africa, as well as an additional method for identification of adult S. sanctipauli and S. yahense. Analysis of the hydrocarbons by GC/MS showed them to be straight chain and branched saturated hydrocarbons ranging from C22-C35. The technique is simple in respect of field methods of collection, and thus holds considerable promise as a means of identifying S. damnosum complex flies throughout the area of onchocerciasis transmission in Africa. PMID- 4023561 TI - Pancreatic oncofetal antigen in the detection of experimental cancer of the pancreas. AB - A hamster serum protein which reacted with anti-human pancreatic oncofetal antigen (POA) was identified in sera from hamsters with varying types of pancreatic pathology. Hamsters were treated with N-nitrobis-(2-hydroxypropyl) amine, and histological findings in the pancreas were correlated with hamster POA. The cross reactivity of anti-human POA with hamster POA was poor. As a result, the sensitivity of this assay was too low to permit its use in serologically discriminating carcinogen-induced pancreatic cancer from other pancreatic pathologies. A specific antiserum and assay system to hamster POA may overcome this problem. PMID- 4023562 TI - Cellular and molecular changes in 3T3 cells transformed spontaneously or by DNA transfection. AB - Transformed cell lines have been selected following exposure of NIH 3T3 cells to a calcium phosphate precipitate containing DNA from: the human colon carcinoma cell line, SW 480; the cloned Harvey sarcoma virus ras gene; the parental NIH 3T3 cell line; or no DNA (a spontaneous transformant). Unlike the parental 3T3 cells, each of these lines readily formed malignant spindle cell tumors in Swiss nu/mu mice. Southern blots confirmed the presence of the human homologue of the Kirsten ras gene in the cells transformed by SW480 DNA, and the Harvey ras gene in the cells transformed with that cloned sequence. The morphology of each of the lines was different, the cells transformed with the human and viral ras genes being the most aberrant (but not identical) and forming the most extensive foci in culture. These ras transformed lines also exhibited anchorage-independent growth, while the two other transformed lines did not. Both of the ras transformed lines, as well as the spontaneously transformed line, exhibited a pronounced disruption of actin microfilament structure. Two-dimensional gel electrophoresis of 35S methionine-labeled peptides revealed that these three lines also had a marked decrease in an acidic peptide of 32K daltons. PMID- 4023563 TI - Neuron-specific enolase in neuroblastoma and other pediatric tumors: a comparative nude mouse and clinical investigation. AB - Neuron-specific enolase (gamma-subunit isozyme) in extracts of human neuroblastomas and other tumors in children was measured by means of a radio immunoassay in order to elucidate the rationale for clinical determination of its serum concentrations in patients. Surgical specimens as well as tumors xenotransplanted in nude mice were studied. The neuron-specific enolase (NSE) concentrations in extracts of xenografted and surgical neuroblastomas were 1,733.2 +/- 677.3 (range; 883-2,659) ng/mg protein and 1,735.3 +/- 941.1 (559 2,933) ng/mg protein, respectively, while other pediatric tumors examined showed much lower levels of NSE: 121.5 +/- 146.1 (22-374) ng/mg protein in xenografts and 17.7-610 ng/mg protein in surgical specimens. Sera of nude mice bearing human neuroblastomas also showed NSE concentrations ranging from 1,102 to 4,400 ng/ml, very much higher than those in sera of nude mice without tumors or with other pediatric tumors. These results tend to confirm the specificity of NSE for neuroblastoma, and the difference in NSE concentrations among five neuroblastoma xenografts is discussed in relation to their cytogenetic characteristics. PMID- 4023564 TI - Pyruvate kinase isozymes and dedifferentiation of (neuro-)ectodermal tumors. AB - This paper describes the isozyme composition and regulatory properties of pyruvate kinase (PK) from well-differentiated (DMTC) and undifferentiated (AMTC) medullary thyroid carcinomas of the rat. These tumors were chosen as an animal model for human (neuro-)entodermal neoplasms differing in their degree of differentiation. The results were compared with human medullary thyroid carcinomas (MTC) and phaeochromocytomas. AMTC were characterized by increased PK activity, a higher apparent S0.5 for phosphoenolpyruvate, enhanced inhibition by alanine, presence of predominantly M2-type isozyme and loss of M1-type-containing hybrids as compared to DMTC. The alterations in PK isozyme expression and hence kinetic behaviour could not be demonstrated in human MTC or phaeochromocytomas due to the apparently well-differentiated nature of these tumors and the presence of M2-type isozymes. These results are discussed with reference to the nature and significance of PK isozyme shifts found in other tumors. It is suggested that the determination of PK isozyme composition might prove useful in the diagnosis of nueroectodermal neoplasms originating from tissues not primarily expressing M2 type isozyme(s). PMID- 4023565 TI - Characterization of the tumorigenic and metastatic properties of a human pancreatic tumor cell line (AsPC-1) implanted orthotopically into nude mice. AB - An orthotopic xenograft of the human pancreatic tumor was established by inoculating human pancreatic tumor AsPC-1 cells into the duodenal lobe of the pancreas of the athymic nude mouse. Microscopically, the xenograft was formed by a heterogeneous population of tumor cells, displaying moderately to poorly differentiated adenocarcinomas with the latter capable of invading the adjacent pancreatic islets or non-endocrine elements. At 4 weeks post-transplantation, the tumor was detectable as a focal implant at the site of inoculation and thereafter grew progressively leading to extensive visceral invasion and metastasis. In contrast to the subcutaneous xenograft, all the mice (9/9) bearing orthotopically transplanted tumor developed secondary foci in the gut and at the peritoneum, with 7, 6, and 4 animals showing additional kidney, mesenteric lymphnodal, and diaphragm metastases, respectively. Distant metastases in the lungs were found in 3 mice and malignant ascites developed in two. Human pancreas cancer associated antigen was detected in the tumor, serum, and ascitic fluid of the mice at 63 +/- 24 micrograms/gm, 15 +/- 6 micrograms/ml, and 5 micrograms/ml, respectively. The finding of these regional and distant metastases was quite different from that in the animal bearing subcutaneously xenografted tumor where no metastases to internal organs was observed. The results suggest the potential use of this experimental system in tumor biology and antigen expression of human pancreatic cancer in vivo. PMID- 4023566 TI - [Levels of lead, cadmium, arsenic, copper, zinc, iron and manganese of the muscles of slaughterhouse animals. II. Muscle tissue of cattle 1975-1983]. PMID- 4023567 TI - [Laboratory evaluation of the nutritive value of average daily diets of selected population groups in Poland. II. Nutritive value of protein]. PMID- 4023568 TI - [Laboratory evaluation of the nutritive value of average daily diets of selected population groups in Poland. III. Levels of calcium, phosphorus, magnesium, iron and potassium]. PMID- 4023569 TI - [The quality of nutrition of children in nurseries]. PMID- 4023571 TI - [Dynamics of growth and maturation of girls in the Upper Silesia Industrial District]. PMID- 4023570 TI - [Sodium sorbate as a preservative for ready-to-eat foods]. PMID- 4023572 TI - [Psychophysical development of children raised in children's homes and in the family]. PMID- 4023573 TI - [Sanitary-hygienic evaluation of swimming pools in Bydgoszcz based on studies of water quality. I. Microbiological studies]. PMID- 4023574 TI - [Evaluation of the daily intake of mercury, lead and cadmium in the meals of selected population groups]. PMID- 4023575 TI - [Occult damage to the femur neck in senile-/inactivity-osteoporosis]. AB - Fractures of the femoral neck in elderly patients are often a complication in osteoporosis. Diagnosis of fractures with displacement and compression of fragments is quite easy. The negative radiograph in old patients complaining of hip pain is generally considered a characteristic feature of presenile osteoporotic pain. Clinical examples present patients with hip pain caused by occult injuries of the femoral neck. They should be regarded as imminent fractures and adequately treated. Bone scan is very helpful in the early detection of such occult osteoporotic injuries. PMID- 4023576 TI - [Objective procedure for determining the contrast-detail-diagram in computed tomography]. AB - Complete information on the power of resolution of a computer tomograph is supplied by the contrast detail diagram. The authors present the development of an objective determination method. Evaluation of the images of a wire and water phantom is performed via the computer of the CT equipment. This method yields objective and reproducible results. PMID- 4023577 TI - [Ergotamine-induced disorders of the peripheral blood circulation--a case report]. AB - Ergotism with severe arterial circulatory disorders, sometimes leading to amputation of the leg, is a severe complication following application of drugs containing ergotamine. Often the diagnosis is made by the typical angiographic findings. The history, clinical course and a new treatment in a very severe case is reported. PMID- 4023578 TI - [Circumstances of detection and strategy in pediatric urology]. PMID- 4023579 TI - [Internal urinary malformations]. PMID- 4023580 TI - [External malformations of the urinary tract]. PMID- 4023581 TI - [Urinary lithiasis in children]. PMID- 4023582 TI - [Adrenal phlebography in the etiological diagnosis of arterial hypertension]. PMID- 4023583 TI - Psychologic investigation in the estimation of the effects of hypotensive therapy in hypertensive patients working in the railway and highway traffic security. AB - Sixty four hypertensive patients working in railway and highway traffic security (engine operators, drivers, switchmen, etc.) were studied clinically and paraclinically and were also submitted to psychologic tests since the characteristics of their work requires a normal psychophysical state. The patients investigated, mostly males (93%), mean age 45.2 years, had essential arterial hypertension (AH) stages I (36 patients) and II (28 patients). After 3-4 days of low salt diet, therapy with propranolol (8 to 360 mg/day) and diuretics was started in most of the patients. In 8 patients with AH stage II, hydralazine (50-100 mg/days) was added to the treatment. The psychologic tests used were: the pencil-paper test "Labyrinth", "Barrage" and "A.D. Praga" and a motor test "Piorkowsky" used 2 times, i.e., before and after treatment. After 15 days of treatment the blood pressure values decreased: systolic from a mean value of 155 +/- 25 mmHg to 136 +/- 81 mmHg; diastolic from 102 + 18 mmHg to 84 +/- 11 mmHg. The marks for the psychologic test were: very poor, poor, medium, good, very good. The post-therapeutic changes obtained were noted in percentages. Improvements obtained: for the "Praga" test in 54% of the patients, for the "Barrage" in 44% of the patients and for the "Labyrinth" in 66% of the patients. Improvements for the first "Piorkowsky" test (slow rate stimuli) were obtained in 54% of the patients and for the second (faster rate stimuli) in 69%. No decrease of psychologic performance was observed in any of the patients. Therefore the psychologic tests used may contribute to the follow-up of the effectiveness and of the side effects of modern hypotensive therapy especially in patients working in traffic security in whom the psychophysical state should be at its best. PMID- 4023584 TI - The value of some cytoenzymochemical investigations of the leukocytes and platelets in estimating the effects of occupational exposure to benzene, vinyl chloride and carbon disulphide. AB - Cytoenzymochemical investigations were performed on the leukocytes and platelets from 2,782 workers occupationally exposed to benzene, vinyl chloride or carbon disulphide, in view of detecting the eventual occurrence of cytologic metabolic disorders induced by these chemical substances. The cytomorphologic aspects and the cytoenzymochemical parameters studied, such as the leukocyte alkaline phosphatase, endolymphocytic glycogen, lymphocytic nucleolar RNA amounts (revealed by the lymphocyte nucleologram), as well as the platelet counts have shown some abnormal values, whose severity was related to the time of exposure to toxic chemicals. The results obtained demonstrate the utility of such tests for an early detection of some metabolic disorders of the endolymphocytic proteins, carbohydrates or lipids, in view of preventing the occurrence of more severe pathologic consequences. PMID- 4023585 TI - The metabolic behaviour of the lymphocytes from serous effusions in various benign internal diseases. AB - The functional status of the lymphocytes from pleural or peritoneal effusions occurring in 148 patients with various internal diseases such as tuberculosis, liver cirrhosis, heart failure and pneumonias was studied by laboratory investigations including morphologic examination, cytoenzymatic, cytochemical and biochemical tests for determining the scores of acid phosphatase activity and of endolymphocytic glycogen, as well as the presence of nucleolar RNA. These values were found increased in the fluids from tb patients and in some cases of liver cirrhosis, heart failure and metapneumonic pleurisies. The variations of these parameters are assumed to provide information on the metabolic behaviour of the lymphocytes present in these fluids and on their participation to the immune, inflammatory processes which occur in the course of some of the diseases investigated. PMID- 4023586 TI - Study of respiratory and immunologic changes in the workers of a poultry farm. AB - The present investigation was designed to the study of respiratory symptoms and immunologic changes in workers of a poultry farm, chronically exposed to various organic allergens (avian, fungi, etc.). The group studied included 202 exposed subjects (109 at the slaughter house, 93 on the farms) and 100 controls. Although the group was chiefly made up of young women, non-smokers, exposure to avian allergens increased the prevalence of respiratory symptoms. Thus, coughing and expectoration was noted in 8.2% of the workers in the slaughter house and 10.7% of those on the farms, wheezing being present especially in the latter (13.9%). An apparently obstructive pulmonary function was observed in 16.10% of the farm hands and 1% of controls. The study of humoral immunity suggested that the presence of precipitation antibodies (76% positive reactions in the farms, 63% in the slaughter house, 44% among the controls) indicated exposure to avian allergens rather than the clinical and radiologic presence of the disease. PMID- 4023587 TI - Effect of long-term therapy with transfer factor in rheumatoid arthritis. AB - Specific immunotherapy with transfer factor (TF) was used in a chronic experiment in a group of 50 female patients with rheumatoid arthritis (RA) stage I-III. The patients were followed up for 24 months, clinical and biologic examinations being repeated every 3 months. In this period the patients received beside the basic nonsteroid antiinflammatory therapy, one unit TF every week over a period of 6 months then one until TF every month (10 patients) to the end of experiment. Of the 50 patients 15 (30%) did not respond to the therapy and the experiments had to be interrupted after 6 months. Excellent, very good and good results were obtained in 35 patients (70%). In 12 patients the response was good but the dose of TF had to be increased to two units/week in the first 6 months. In 13 patients the results obtained were very good and therapy with nonsteroid products + TF was continued even after the first 6 months. In 10 patients with RA stage I the results obtained were excellent and after 6 months the nonsteroid therapy could be interrupted and the therapy was continued only with one unit TF every month. The study confirmed the fact that specific immunotherapy with TF represents an important adjuvant in the treatment of rheumatoid arthritis (RA). PMID- 4023588 TI - A method which improves anatomo-clinical correlations in ischemic heart disease. AB - A study carried out on 595 unselected subjects aged 21-55 years who had died of accidental causes and on 56 selected patients who had died of myocardial infarction showed that the light microscopic examination of coronary branch vessels led to an obvious improvement of anatomo-clinical correlations in ischemic heart disease. These branch vessels included atherosclerotic plaques in 51% of unselected subjects 51-55 years old, dead of accidents and in 73% of selected patients dead of myocardial infarction. Severe stenotic plaques of possible clinical significance were found in 14% of subjects dead of accidents and in 48% of patients dead of myocardial infarction. In these cases the atherosclerotic involvement in the major coronary arteries (left anterior descending, circumflex and right coronary arteries) did not reach the level of possible clinical significance (greater than or equal to 75% reduction of the vessel diameter). Several examples emphasize the importance of stenotic lesions in the first diagonal, first septal, posterior descending, left marginal and right marginal vessels, as well as in the vessels supplying the sinoatrial and atrioventricular nodes for an adequate anatomo-clinical correlation in ischemic heart disease. PMID- 4023589 TI - Intimal thickening and atherosclerotic involvement of the left main coronary artery. AB - A post mortem study carried out on 886 apparently healthy children, adolescents, young and mature adults of an unselected population sample of Bucharest who died of accidental causes, revealed that the left main coronary artery acted as an atherosclerosis-resistant segment of the coronary arterial bed. The importance of this natural resistance was demonstrated by means of a comparative investigation involving the degree of intimal thickness, the intima thickness versus media thickness ratio, the per cent of subjects with atherosclerotic plaques and the obstructive character of these plaques. These parameters were examined in 6 selected topographic sites: (a) at 5 mm distal to the origin of the left main coronary artery, compared with those detected at 10 mm and 20 mm distal to the point of origin of the anterior descending artery; (b) at 5 mm from the aortic origin of the right coronary artery, compared with those recorded at 20 mm and 30 mm from the same point of origin. PMID- 4023590 TI - Circulating immunoglobulins--IgA, IgG and IgM--in adults and children with idiopathic, never treated, epilepsy, and the effect thereon of mono-drug treatments. PMID- 4023591 TI - Improvement by CSF spectrophotometry of diagnosis in acute intracerebral hemorrhages not revealed by visual and microscopical classical examination of CSF. PMID- 4023592 TI - Orienting reaction in patients with multiple sclerosis. PMID- 4023593 TI - Retrospective epidemiology in multiple sclerosis and significance of canine morbillivirus in the illness etiology. PMID- 4023594 TI - Diagnostic value of automatically averaged evoked cerebral potentials for lesions of somatosensory pathways. PMID- 4023595 TI - [Grammatical agreement performances and strategies in aphasics]. PMID- 4023596 TI - [The environmental system, its study and management]. PMID- 4023597 TI - [Changes in the blood picture and iron stores during pregnancy and after labor]. PMID- 4023598 TI - [A noninvasive method of studying myocardial contraction]. PMID- 4023599 TI - Does general anaesthesia affect the child's auditory middle latency response (MLR)? AB - Auditory MLR and ABR were recorded simultaneously in 9 children under general anaesthesia, after electrocochleography had demonstrated a normal hearing threshold. In contrast to the ABR components which in all cases appeared to be clearly recognizable, and with latencies within the normal range, MLR revealed gross abnormalities represented by instability of the components and abnormal latency of the detectable peaks. Since such variations in the MLR pattern may be thought of as a direct consequence of general anaesthesia, it seems likely that these potentials reflect a neural activity which, in children, is affected by CNS drugs. PMID- 4023600 TI - Questionnaires on desirable properties of hearing aids. AB - Three questionnaires were presented to 49 hearing-impaired patients. They were asked to rank different properties of behind-the-ear hearing aids with regard to their importance. The first questionnaire dealt with physical properties such as size, weight, and battery-cost, but also with the importance of good sound quality. The second questionnaire focused on the relative importance of various sound quality dimensions, such as softness, clarity, fullness, and others. The third questionnaire asked for suitable sound programs to be used in the procedure of hearing aid fitting in the clinic. Sound quality scored the highest rank by 43 of the patients, and clarity was considered to be the most important sound quality dimension. The most preferred sound programs included male and female voices with or without a background of other voices. PMID- 4023601 TI - Suppression by tones of the click evoked compound action potential in the normal and pathological guinea-pig cochlea and in man. AB - The compound action potential (AP) to a broad-hand click stimulus, recorded from the round window in guinea-pigs and from the promotory in humans, was suppressed by a tonal stimulus. The degree of suppression depended upon the relative levels of the click and masking tones and upon the tone frequency. Using a fixed 50% suppression criterion, the tone-on-click masking revealed that for near threshold click levels a relatively narrow population of nerve fibres contributed to the AP. Both for threshold and suprathreshold clicks the population of neurones contributing to the AP was centred at the minimum of the AP audiogram with no shift toward higher frequency as the click level was raised. The shape of the response area revealed by tone-on-click masking is similar to that shown by tone on-tone masking. Application of the tone-on-click masking technique to Kanamycin poisoned guinea-pigs and to humans with cochlear lesions indicated that useful information about residual hearing could be obtained even at very low frequencies. PMID- 4023602 TI - Effect of tone-burst frequency on fast and slow components of auditory brain-stem response. AB - By means of digital filtering, averaged auditory brain-stem responses (ABR) were divided into slow and fast components with frequency compositions of 50-300 Hz and 400-1 500 Hz, respectively, and the relation of the two components to stimulus frequency was investigated. Tone bursts with a rise-decay time of two periods of the chosen frequency with no plateau (2-0-2) and with a 4 ms rise decay time with no plateau (8 ms duration) were used as acoustic stimuli. Tone burst frequencies were 0.5, 1, 2, 4 and 8 kHz at an intensity level of 40 dB nHL. The amplitude ratio of wave V of the fast component to the slow component decreased with decreasing stimulus frequency, and it remained almost unchanged at each stimulus frequency regardless of the rise-decay time of the stimuli. From these results, it became clear that the frequently-mentioned audiometric difficulties for lower frequency stimuli in ABR testing are related mainly to the low amplitude of the fast component for the frequency range below 1.0 kHz. The slow component, with relatively large amplitude for the low-frequency stimuli, is regarded as the most useful index in the ABR for threshold estimation of hearing. PMID- 4023603 TI - Interpeak intervals of auditory brainstem response, interaural differences in normal-hearing subjects and patients with sensorineural hearing loss. AB - ABR recordings were made on 31 normal-hearing subjects and 253 patients with sensorineural hearing loss (86 patients with unilateral hearing loss, 61 patients with asymmetrical hearing loss, 34 patients with symmetrical hearing loss, 55 patients with noise-induced hearing loss and 17 patients in the late chronic stage of Meniere's disease). In the patient group with unilateral hearing loss, the mean interpeak interval (IPI) I-V was significantly shorter than in normal hearing subjects. The interaural IPI differences provide a sharp criterion for early detection of acoustic neuroma. The calculation of the 95%-limits (means + 1.96 SD) showed that in patients with normal hearing or with unilateral or symmetrical hearing loss an interaural difference in the IPII-V greater than 0.2 ms has to be considered as an indication of a neuroma or any other brainstem abnormality. In patients with asymmetrical or with noise-induced hearing loss, the limit is 0.3 ms. In contrast to the frequently recommended interaural wave V latency difference criterion, the interaural IPI difference criterion requires no correction for audiogram differences. PMID- 4023604 TI - Estimation of auditory brainstem response, ABR, by means of Bayesian inference. AB - The present paper describes a new method to estimate the auditory brainstem response when the electrical activity from the recording electrodes displays non stationarity, i.e. varies between low and high levels. The method is based on a statistical approach called Bayesian inference and weights the individual components (here blocks of 250 sweeps) inversely proportional to the level of the noise activity during the recording. Fifty sets of data from 10 consecutive patients obtained during stimulation at high intensity are used to evaluate the difference between the classic averaging and the present method which is called Bayes estimation. In approximately 30% of the cases, a significant all-over improvement is obtained by the new method. The classic averaging technique would here require 50% more sweeps to be taken to obtain the same precision of the ABR estimate, on average. Also the latency and amplitude parameters of the Jv wave complex are evaluated and it is shown that the parameter variance decreases by a factor of approximately 2 by using the Bayes estimation. The new technique is compared with a similar technique recently presented by Hoke et al. (1984) and the differences and similarities are discussed. PMID- 4023605 TI - Comparison between thresholds obtained with pure-tone audiometry and the 40-Hz middle latency response. AB - Threshold determinations were performed with the 40-Hz MLR method on 20 individuals of varying age, from one month to adult age. The total number of threshold measurements was 105 in the frequency range from 0.25 to 8.0 kHz. Eighty determinations were performed on persons with hearing loss of 40 dB HL or more and the remaining 25 on normal-hearing persons. One of the investigators estimated the MLR thresholds without any knowledge of the results of the psychoacoustical tests. The MLR thresholds were nevertheless in good concordance with those obtained with behavioural tests. The sensitivity of MLR audiometry for detecting a hearing loss was 100%, and the specificity for recognizing normal hearing was 91%. In 27% of the measurements the thresholds obtained with both methods were identical; in 67% the difference was +/- 15 dB. When the MLR thresholds were estimated by the dependent investigator the corresponding figures were 34 and 74% respectively. When the MLR test was performed on children who were sound a sleep, the MLR thresholds were elevated by about 40 dB. PMID- 4023606 TI - Does physicians' knowledge of costing related to clinical decision making change the consumption of resources despite unchanged medical standards? AB - The problem formulation of the present project was as expressed in the title, with a secondary approach that if a difference could be measured, its magnitude would have to be evaluated in relation to the total bed day price of the study period, amounting to DKR 3600. The investigation comprised a hidden and an open phase, each covering 2 months, April-May and September-October 1983. During the second phase all physicians of the department inserted prices in the case records for all clinical decisions, consumption of utensils, drugs, X-ray investigations, clinical-chemical analyses, clinical-physiological analyses, ultrasonographies, endoscopies, and visits by specialist consultants. The price setting was done from a price catalogue made for the study, in accordance with either existing prices or prices calculated for the present purpose. During the first hidden phase it was possible to calculate the total price of all clinical interventions by secondarily applying prices as in phase 2. In this manner it was possible to create a starting level representing a period in which none of the participants had any idea of the later health economy study. In both phases 293 patients entered, with an identical distribution of age, sex, admittance periods, and so forth. The total sum of registered interventions for phase 1 was DKR 612,839 and for phase 2, DKR 532,515, giving a reduction of approximately 13%, corresponding to total expenses per day within the subgroups mentioned of DKR 199 in phase 1 and DKR 176 in phase 2. These sums must be judged in relation to the bed day price for the study phases.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4023607 TI - Irritable bowel syndrome--prognosis and diagnostic safety. A 5-year follow-up study. AB - The irritable bowel syndrome is the commonest diagnosis in gastroenterological clinics, although diagnostic criteria and investigatory programs vary. To elucidate the diagnostic safety and prognosis of the syndrome, a retrospective study was conducted. One hundred and twelve consecutive patients with irritable bowel syndrome as the final and only abdominal diagnosis in the period 1977-79 were followed up in 1984. Seventeen patients died during the follow-up period; two of these were considered diagnostic failures (chronic pancreatitis and pancreatic cancer). Of the remaining 95 patients, 93 were available for the follow-up study. Three diagnostic failures were found (gallbladder stones, kidney stone, thyrotoxicosis). The diagnostic failure rate was accordingly 4.5% (5/110). Half of the patients had unchanged or aggravated symptoms at the follow-up study, independent of treatment. The only predictor of a poor prognosis was abdominal surgery before the diagnosis. PMID- 4023608 TI - A method to prevent recanalization of the transected bile duct in the rat. AB - The purpose of this study was to develop a surgical technique for bile duct occlusion in the rat which would prevent restoration of biliary drainage. In three successive series of animals the surgical technique was modified from ligation and transection to ligation and transection with resection and, finally, to ligation and transection with transposition of the distal end behind the stomach-duodenum. In these three groups recanalization was observed in 4 out of 9, 1 out of 9, and 0 out of 19 animals, respectively. Bilirubin levels in plasma monitored in the last group showed that a stable cholestatic jaundice was maintained for at least 6 weeks. The results suggest that transposition of the distal transected end of the bile duct below the stomach-duodenum will effectively reduce the chance of recanalization and thus make study of long-term extrahepatic cholestasis in the rat more practical. PMID- 4023609 TI - Biliary secretion of bilirubin and lipids in chronic cholestatic liver disease. AB - Relationships between biliary bilirubin and lipid secretions were studied in patients with chronic cholestatic liver disease, mainly primary biliary cirrhosis. The bilirubin secretion rate in the patients was not significantly different from that in the controls. However, the bilirubin output per phospholipids, per bile acids, and per phospholipids plus bile acids was high, especially at low bile acid secretion rates. Thus, the bile of the patients with chronic cholestatic liver disease appears to be frequently 'supersaturated' with bilirubin. This metabolic abnormality may be associated with an increased risk of pigment stone formation in patients with cirrhosis. PMID- 4023610 TI - High gastric bile acid concentration in prepyloric ulcer patients. AB - The intragastric concentrations of bile acid (BAC) and pH were measured over 24 h in 13 patients with duodenal (DU), in 11 with prepyloric (PU) ulcer disease, and in 12 healthy controls. Large fluctuations in bile acid concentration occurred for individuals from all three groups. PU patients had BACs higher than DU patients and controls both during the day (p less than 0.01 and p less than 0.001) and at night (p less than 0.001 and p less than 0.05). Controls had a significantly higher BAC during the night than the day (p less than 0.001). The acidity was significantly higher in DU patients than in controls both during the day and night (p less than 0.05). Compared with PU patients, the DU patients had higher acidity at night (p less than 0.01). PMID- 4023611 TI - Idiopathic bile acid diarrhoea reconsidered. AB - Two new cases of a rare entity provisionally coined 'idiopathic bile acid diarrhoea' are reported and compared with previous cases. The diarrhoeal syndrome has been identified as a cholegenic enteropathy. In the absence of conventional ileopathy the cause of the bile acid loss is obscure, but it is hypothesized that it may be due to a relative deficiency in ileal absorptive sites for bile acid anions. So far the diagnosis has partly been based on measurements of faecal bile acid losses. It is suggested that a carefully conducted therapeutic trial with cholestyramine may be almost equally helpful. PMID- 4023612 TI - Observer variability in upper gastrointestinal fiber endoscopy. AB - The reliability of esophagogastroduodenoscopy (EGD) was evaluated in 71 patients. The study was designed as a comparison between the separate protocols written by two endoscopists at each EGD. The results showed an over-all disagreement of 32% between observers. When the results were correlated with endoscopical experience, a significantly higher proportion of false-negative results was found among endoscopists with experience of less than 500 EGDs compared with a more experienced group of investigators. No difference was found between residents in training (less than or equal to 200 EGDs) and those with intermediate experience (200-500 EGDs). The implications with regard to repeated training programs and authorization of endoscopists are discussed. PMID- 4023613 TI - Hypersecretion of gastric acid in a representative Finnish family sample. AB - To evaluate the family behaviour of acid secretion and particularly of 'hypersecretion', we have examined by pentagastrin test and direct vision gastric biopsy 342 subjects with a normal mucosa or superficial gastritis of the body mucosa, collected from a large family sample of the Finnish population. Acid output (AO) was expressed in terms of fat-free body weight (FFB), which eliminates the sex factor found by other expressions of AO. Subjects with values above 1.0 mmol/h/FFB were considered 'hypersecretors' (14 subjects, or 4% of the whole sample). They differed from the whole sample with regard to a high prevalence of signs of duodenal ulcer disease, of high serum pepsinogen, and of blood group O and lack of gastric antibodies and of high serum gastrin levels. The Fisher distribution test showed a significant family aggregation of AO values. In addition, at low AO levels there were subgroups with distinct gaps between them. This finding suggests the effect of genetic variation rather than of a common family environment. The occurrence of higher AO values in sibs but not in children of 'hypersecretors' seems to rule out the possibility of a dominant Mendelian inheritance. These present results are considered to be best compatible with a multigenetic mode of inheritance of gastric hypersecretion. PMID- 4023614 TI - The sequelae and course of chronic gastritis during a 30- to 34-year bioptic follow-up study. AB - Three hundred and seventy-seven subjects with different conditions of the gastric body mucosa have been followed up for 30-34 years, first by the 'blind' suction biopsy method and since 1973-1976 by the direct-vision endoscopic method. Body gastritis revealed a distinct worsening trend during the whole follow-up period. However, during the last follow-up period some slowing down of the process was also discernible. In the antrum there was a distinct healing trend during that period. Thus all cases of distinct atrophic gastritis limited to the antrum and found at the re-examination in 1973-1976 had disappeared during the last follow up period owing to regression of the antral or continuation of the body process. On the other hand, a considerable proportion of cases of diffuse antrofundal atrophic gastritis found in 1973-1976 appeared in 1983-1984 in the 'pure' body atrophic gastritis group, obviously due to regression of the antral process. This indicates the existence of an alternative pathway via diffuse antrofundal atrophic gastritis for the development of atrophic gastritis limited to the body area. The occurrence of parietal cell antibodies was on the whole a poor indicator of the progression of atrophic gastritis. However, the development of the end-stage (severe) atrophic gastritis was significantly associated with their presence. Atrophic changes of the body mucosa were not found in 1983-1984 in any cases of duodenal ulcer disease, whereas in patients with gastric polyps atrophic gastritis affecting only the body was, as a rule, present. No case of gastric carcinoma was detected during the last follow-up examination. PMID- 4023615 TI - Short-chain fatty acids in the small-bowel bacterial overgrowth syndrome. AB - The short-chain fatty acids (SCFAs) have been measured by gas chromatography in fasting jejunal secretions, saliva, and feces from 8 patients with the small bowel bacterial overgrowth syndrome (BO) and 9 control patients; in jejunal secretions and saliva from 6 healthy subjects; and in feces from 20 healthy subjects. The concentrations of SCFAs (median (range), mumol/l) in jejunal secretions of BO patients were as follows: total, 990 (210-12,370); acetic acid, 650 (170-6770); propionic acid, 110 (16-3070); isobutyric acid, 26 (1-310); n butyric acid, 90 (12-1340); isovaleric acid, 35 (2-680); n-valeric acid, 7 (3 200). In BO patients the total concentration of SCFAs in jejunal secretions was approximately four times higher than in control patients (p less than 0.01) and in healthy subjects (p less than 0.025). The relative distribution of the acids resembled the distribution found in feces more than that of saliva or the normal jejunal secretions. These findings indicate that patients with BO have a colon like flora in the small intestine and that the main part of the SCFAs in the jejunal secretions of these patients is produced by the altered microbial flora in the jejunum. Combined with other tests, analyses of intestinal SCFAs may prove to be valuable in the diagnosis of small-bowel bacterial overgrowth. PMID- 4023616 TI - Absorption of food cobalamins assessed by the double-isotope method in healthy volunteers and in patients with chronic diarrhoea. AB - To make a food preparation containing radioactively labelled cobalamins, rabbits were given repeated injections with 57Co-labelled cyanocobalamin. The liver was removed, homogenized, and fried for 1 min or boiled for 30 min. Of the radioactivity in the fried homogenate 41.7% was recovered in the centrifuged supernatant compared with 50.8% in the boiled homogenate. The radioactivity in the supernatants had a molecular size close to that of free 57Co-labelled cyanocobalamin. Forty-two per cent of the radioactivity in the whole homogenate had been incorporated into 5-deoxyadenosyl-, 10% into methyl-, and 16.5% into hydroxy-cobalamin. To assess the validity of a double-isotope method for measuring the intestinal absorption of doses of the 57Co-labelled liver cobalamins, 51CrCl3 was used as a non-absorbable marker. In 14 healthy volunteers the correlation coefficient between the absorption measured by the double-isotope technique and the faecal excretion test was highly significant (r = 0.96, p less than 0.005), and there was only a small variation in the 57Co/51Cr ratio in successive stool collections. In 11 patients with chronic diarrhoea there was a significant correlation between the absorption measured by the double-isotope technique and the faecal excretion test (r = 0.92, p less than 0.005), but in some patients there was considerable variation in the 57Co/51Cr ratio in successive stool collections. PMID- 4023617 TI - On the mode of action of the pentagastrin test in the carcinoid syndrome. AB - Provocation with pentagastrin (PG) (0.6 micrograms/kg intravenously) causes a release of serotonin (5-hydroxytryptamine (5-HT] in excess of the metabolizing capacity associated with carcinoid symptoms and a moderate fall in systemic arterial blood pressure in patients with midgut carcinoids and hepatic metastases. In this study PG also caused a release of 5-HT into portal circulation of anesthetized cats with stable peripheral levels of 5-HT in whole blood, indicating an effective hepatic metabolization. A similar response was obtained in the same animal when the PG test was repeated after 3 h. PG provocation was also performed in animals before and after adrenalectomy. Adrenalectomy seems to prevent the PG-induced release of 5-HT into portal circulation, indicating involvement of an adrenal mechanism. PG does not induce 5 HT release from cell suspensions of midgut carcinoid tumors, but such release was induced by incubation with adrenoceptor agonists. These findings indicate the presence of adrenoceptors on carcinoid tumor cells. The mode of action of the PG test may therefore be activation of such adrenoceptors by catecholamines, released from the adrenal medulla at the fall of arterial blood pressure at PG provocation. PMID- 4023618 TI - Hyperplasia or neoplasia. Macroscopic versus microscopic appearance of colorectal polyps. AB - Small light-red sessile colorectal polyps, 1-5 mm in diameter, are generally believed to be hyperplastic (non-neoplastic), whereas polyps that are dark-red in contrast to the surrounding mucosa are thought to be adenomas. This hypothesis was tested prospectively in a series of 209 polyps removed by one endoscopist in a 6-month period. A 'blinded' pathologist provided the histopathological diagnosis. Twenty-two per cent of polyps described as hyperplastic by the endoscopist were adenomas, whereas 40% of those believed to be adenomas, 1-5 mm in diameter, were hyperplastic. The diagnostic effectivity of the endoscopist increased with increasing size of the polyps. In conclusion, all colorectal polyps must be removed to prevent possible precancerous lesions from being left behind and to define a group of patients with increased risk of new adenomas, in whom follow-up examinations should be considered. PMID- 4023619 TI - Crohn's disease. A long-term study of the clinical course in 186 patients. AB - A series of 186 patients treated for Crohn's disease during the period 1956 to 1968 has been followed up in 1970, 1975, and now in 1983. Among 173 patients operated on there were 89 recurrences (52%). After a follow-up time greater than 14 years (mean, 18 years) 'radical' resections at the first operation gave a lower recurrence rate (31%), fewer reoperations, and a better quality of life compared with non-'radical' resections (recurrence rate, 83%). The quality of life estimated for all patients alive in 1983, 152 patients, was good in 89%; 8.6% had moderate subjective symptoms, and 2.6% had pronounced subjective symptoms. With an increasing follow-up time there was no decrease in the patients' quality of life. Ileorectal anastomosis did not give very good results; proctocolectomy and ileostomy, however, gave good results. Regular investigation of all patients is of vital importance to give them a good quality of life. PMID- 4023620 TI - Evaluation of the marker technique for measurement of exocrine pancreatic secretion rate. AB - A secretin-cholecystokinin test was performed in 103 patients, representing both normal and reduced exocrine pancreatic function. The duodenum was intubated with a triple-lumen tube. The gastric and duodenal contents were aspirated separately and sampled in 10-min periods. An inert, water-soluble marker (58Co-vitamin B12 dissolved in isotonic saline) was infused at a constant rate into the duodenum. Exocrine pancreatic secretion was stimulated by continuous intravenous infusion of secretin for 60 min and a combination of secretin and cholecystokinin for another 60 min. The total recovery of the infused marker was 80%. The concentration of marker in the aspirate did not vary significantly between consecutive 10-min periods during the last 20 min of the secretin stimulation period or during the last 50 min of the combined secretin-cholecystokinin stimulation period, indicating a steady secretion rate into the duodenum. By means of the marker concentrations in the aspirate, the duodenal volumes were calculated and found to vary significantly less than the aspirated volumes. This finding demonstrates that the duodenal volume calculated from the recovery of an inert marker is a closer estimate of the true volume than that obtained by the usual aspiration technique without a volume indicator. PMID- 4023621 TI - Perception of life event stress in patients with chronic duodenal ulcer. A comparison of the rating of life events by duodenal ulcer patients and community controls. AB - Stress is often claimed by doctors and patients to be an aetiological factor in peptic ulcer disease. The aim of the present study was to investigate whether ulcer patients perceive that they would react more strongly than normal to life event stress. Seventy-three patients with duodenal ulcer and their sex- and age matched controls rated 81 events for the amount of distress and life change they considered the events would cause them personally. With regard to individual events, only one difference emerged: female patients rated promotion at work significantly lower for distress than did controls, when event experience was taken into account. There was a systematic tendency for ratings of male patients to be lower than those of controls. These observations suggest that duodenal ulcer patients do not perceive that their reaction to life events would be in excess of normal. PMID- 4023623 TI - Effect of bile fistulae on vitamin B12 absorption in rats. AB - To study the effect of bile on the absorption of vitamin B12, choledochocolic fistulae were made in 26 rats, and 14 rats were sham-operated. Vitamin B12 absorption 9 days after the operation was significantly reduced in the fistula operated group (median, 36.4%; range, 8.3-61.4%) as compared with the sham operated group (median, 48.5; range, 35.8-75.2). Bile instilled together with vitamin B12 did not increase the absorption. In a second 'short-term' experiment external bile fistulae were made in 20 rats, and 10 rats were sham-operated. Vitamin B12 absorption was measured 14 h after the operation, and in this experiment no reduction was found in the fistula-operated rats. This suggests that bile in the lumen of the small intestine has no direct effect on vitamin B12 absorption, but absence of bile during several days may alter other factors of importance for the absorption. PMID- 4023622 TI - Gastric emptying of liquid before and after gastroplasty for morbid obesity. AB - Gastric emptying of a liquid meal was investigated with a radionuclide method before and 1 week and 3 and 12 months after gastroplasty operation for morbid obesity. Gastroplasty results in a small proximal pouch with a narrow stoma to the remaining stomach. The total gastric emptying was delayed 3 months after gastroplasty (p less than 0.01). Twelve months after gastroplasty, emptying of the proximal pouch was faster than at 3 months (p less than 0.01). This may indicate dilatation of the stoma between the two gastric pouches during this period. Surprisingly, the total gastric emptying 12 months after gastroplasty was not only faster than at 3 months but also faster than before surgery. The explanation, therefore, cannot only be attributed to a dilated stoma, and hormonal mechanisms may be involved. A lack of correlation between preoperative weight and emptying was observed, but because the material consists of only obese subjects, no conclusion can be drawn about the postulated role of gastric emptying in developing obesity. Emptying of the total stomach and of the proximal pouch failed to correlate with postoperative weight losses. The weight loss after gastroplasty evidently bears little, if any, relation to the postoperative changes in gastric emptying of liquids. PMID- 4023624 TI - Upper gastrointestinal and mental symptoms in the irritable bowel syndrome. AB - Gastrointestinal and mental symptoms were assessed in 101 outpatients with the irritable bowel syndrome (IBS). A normal female population was used for comparison of mental symptoms. By definition all patients had abdominal pains and/or change of bowel habits (constipation or diarrhoea, or both) but no demonstrable organic disease. Upper gastrointestinal symptoms without peptic ulcer disease were reported by 87% of the patients. Mental symptoms were reported by almost all patients. Symptoms of anxiety, fatiguability, hostile feelings, sadness, and sleep disturbances were seen significantly more often among IBS women than in the controls. We conclude that patients with IBS frequently have upper gastrointestinal and mental symptoms that should be taken into account in the therapeutic management and evaluation of new modes of treatment. PMID- 4023625 TI - The size of human parietal cells before and 7 days after vagotomy. AB - Gastric biopsies from nine patients were studied before proximal gastric vagotomy (PGV) and 7 days after the operation. The average size of the individual parietal cell and its nucleus were calculated by point-counting stereology. The volume of the nucleus was not significantly altered postoperatively. The median volume of the whole cell was reduced from 4976 micron 3 before vagotomy to 3981 micron 3 after the operation (p less than 0.05). The reduction of the cell volume is sufficient to explain our previous finding that parietal cells constitute a smaller fraction of the mucosal volume 1 week after PGV. PMID- 4023626 TI - Stimulated protein kinase activity during acute pancreatitis in rats. Possible mediation by proteolysis, lipolysis, and bile salts. AB - The rate of protein phosphorylation, as catalyzed by the protein kinase enzymes, was measured in the pancreas of rats with acute experimental pancreatitis. Two different methods were used to induce pancreatitis in rats: retrograde injection of deoxycholate (DOC) into the pancreatic duct, or daily intravenous administration of DL-ethionine. Basal protein kinase activity was elevated in rats with acute experimental pancreatitis. This increase in activity was not dependent on free Ca2+ and did not result from elevated cAMP levels. To assess the possible role of digestive enzymes in protein kinase activation, tissue extracts from healthy controls were subjected to mild treatment with digestive enzymes and DOC. Trypsin, chymotrypsin, phospholipase A, and DOC produced protein kinase activation of a similar magnitude as found in diseased tissue. Results indicate that stimulated protein kinase activity in tissue of animals with acute pancreatitis may arise from the action of digestive enzymes. PMID- 4023627 TI - Diagnostic value of gastrointestinal endoscopy in patients with uncharacteristic abdominal disorders. AB - Endoscopic examinations were performed in 50 patients admitted for uncharacteristic abdominal disorders. Despite previous hospitalizations for the same complaints, no certain diagnosis had been established. Endoscopic retrograde cholangiopancreatography and colonoscopy were performed systematically, whereas gastroscopy was performed only on special indications. Of the 18 patients in whom a primary organic disease was diagnosed, duodenoscopy was of importance in 1 (duodenal cancer), colonoscopy in 3, and gastroscopy in 8 patients. In addition, colonoscopy verified the psychosomatic diagnosis in a patient with melanosis. In the rest of the material cannulation of the pancreatic duct (n = 36) or bile duct (n = 33), colonoscopy (n = 42), or gastroscopy (n = 21) did not show signs relevant to the patients' symptoms. Several of these signs, such as polyps or gallstones, together with the importance of negative examinations in the diagnosis of many patients, add to the value of endoscopic procedures in patients with uncharacteristic abdominal disturbances. PMID- 4023628 TI - Incidence and prevalence of primary biliary cirrhosis in a defined population in Sweden. AB - The incidence and prevalence of antimitochondrial antibody-positive primary biliary cirrhosis (PBC) has been studied within a defined area in Sweden served by one hospital. During the period 1976-1983 the yearly incidence of PBC was 1.4/10(5) inhabitants, and on 31 December 1983 the prevalence was 12.8/10(5) inhabitants. The prevalence is the highest reported so far. At the time of diagnosis half of the patients were clinically asymptomatic. Two of the patients also had celiac disease with osteomalacia responding to a gluten-free diet. Gallstone disease occurred in 30% of the patients. Four patients died--two of liver-related complications, one of colonic carcinoma, and one of staphylococcal septicemia and endocarditis. One further patient, who is still alive, developed hypernephroma. Our results indicate that PBC is a fairly benign disease in most patients, with a slow progress during which they lead a fairly normal life. PMID- 4023629 TI - Effect of cyclosporin A on human neutrophil and monocyte function. AB - The effect of various concentrations of cyclosporin A (CyA), ranging from below peak blood levels to 20 times higher than blood levels of human peripheral blood polymorphonuclear and mononuclear leukocytes, was examined. CyA was found to bind to neutrophils with Kd values in the range of 20-50 nM. CyA at clinically obtainable blood level concentrations had no effect on neutrophil and monocyte chemotaxis, neutrophil oxidative burst, monocyte phagocytosis, or neutrophil bactericidal activity. The data on the release of lactoferrin, a secondary granule substance, from activated neutrophils showed that the calcium ionophore A 23187-induced lactoferrin release was inhibited by treatment of cells with 4 microM CyA, whereas release of lactoferrin from zymosan- or phorbol myristate acetate-activated neutrophils was not affected by the same concentration of CyA. This effect could either be due to differences in the degree of cell membrane perturbation by the various activators or to calcium dependence of neutrophil activation. A third possibility may be that CyA acts at some subsequent steps in the release process of neutrophils. It is concluded that CyA does not interfere with important functions of human phagocytes, the cells that play a major role in the defence against invading microorganisms. PMID- 4023630 TI - In vivo activation of mouse macrophages with beta-1,3-D-glucan-derivatized plastic beads. AB - Macrophages obtained from animals treated with beta-1,3-D-glucan-derivatized plastic beads were greatly stimulated, as judged by morphology, esterase release, and cytostatic effect on L-929 tumour cells in vitro. The pretreatment of mice with such beads conferred an apparent absolute local resistance to an otherwise lethal pneumococcal infection but had no effect on the growth of intraperitoneal AA ascites sarcoma. Moreover, peritoneal cells from animals pretreated with glucan beads did not protect the animals in a Winn assay. PMID- 4023631 TI - Naturally cytotoxic tonsillar leukocytes: phenotypic characterization of the effector population. AB - Human palatine tonsil sections were examined to investigate the distribution of cells bearing the cell surface markers of peripheral blood natural killer (PB-NK) cells. Leu-7+ (HNK-1+) cells were localized predominantly in lymphoid follicles, whereas OKM1-, Mac-1-, and Mo2-labelled cells were found in the epithelial and subepithelial regions and epithelial crypts. OKT10+ cells showed a variable distribution, being found in follicles and interfollicular or subepithelial regions. No. B73.1+ cells could be identified in tonsil sections. Leu-7+ cells appeared not to be responsible for tonsillar natural cytotoxicity, since Leu-7 (HNK-1) antibody- and complement-mediated lysis under conditions that markedly reduced PB-NK activity failed to abolish cytotoxicity, and positive selection by means of the FACS IV gave no enrichment of activity. Similarly, cells labelled with the antibodies B73.1, Leu-11b, OKT8, OKT10, and TDR 31.1 (anti-major histocompatibility complex class II framework determinant) were not enriched with regard to NK activity either. However, positive selection with OKM1, Mac-1, or Mo2 showed that cells bearing these markers were responsible for essentially all tonsillar NK activity. No large granular lymphocytes were identified in such populations enriched for NK activity. The observation that PB-NK cells labelled faintly with Mo2 weakens the argument that a non-adherent mononuclear phagocyte population was responsible for the activity. These data therefore support the existence of heterogeneity within naturally cytotoxic cell populations. PMID- 4023632 TI - Passage of undegraded dietary antigen into the blood of healthy adults. Quantification, estimation of size distribution, and relation of uptake to levels of specific antibodies. AB - The absorption into the blood of ovalbumin (OA) and beta-lactoglobulin (BLG) was investigated in eight healthy adults. Enzyme immunoassays showed up to 10.5 ng OA/ml serum in seven out of eight individuals 2-3 h after a test meal, whereas no BLG was demonstrated. The apparent size distribution of the absorbed OA was investigated by high-pressure liquid gel permeation chromatography fractionation, followed by enzyme-linked immunosorbent assay, which in the fractionated sera showed OA in all eight individuals. OA was found at the elution volume of intact OA and, in addition, was present in high molecular weight fractions, as part of the immune complexes. The serum concentrations of OA could not be clearly correlated to levels of serum and secretory anti-OA antibodies. No significant alterations of the levels of circulating immune complexes could be demonstrated by two antigen-nonspecific assays. The presented data indicate that, for certain dietary proteins, low-grade absorption of apparently undegraded protein into the blood occurs regularly in healthy adults. PMID- 4023633 TI - Cathepsin B activity in human blood monocytes during differentiation in vitro. AB - The activity of cathepsin B was assayed in human blood monocytes during differentiation into macrophages in vitro. Freshly isolated monocytes showed negligible cathepsin B activity. On day 3 in culture the enzyme activity was still very low, but it was markedly increased on day 7, concomitant with the monocytes' morphological differentiation into tissue macrophage-like cells. A further rise in enzyme activity was seen on day 10 in culture. Acid phosphatase activity showed similar, but less marked, increases in human monocytes during 10 days' culture. Generally, higher enzyme levels were seen in monocytes isolated from buffy coat preparations than from whole blood. Both the level and the rate of appearance of cathepsin B activity were further enhanced by endocytosis of carrageenan in the monocytes. Stimulation with endotoxin from Escherichia coli caused variable enzyme responses, as certain pools of human cells expressed cathepsin B activity compared with controls, whereas others showed no change in activity. Endocytosis of carrageenan had no effect on acid phosphatase activity, whereas stimulation with endotoxin led to increased levels of this enzyme activity in all cultures. The present data suggest that a rise in cathepsin B activity may be a component in the differentiation of human monocytes into macrophages. They further indicate separate regulation of lysosomal enzyme activity in human monocytes after some types of stimulation, as previously shown for mouse macrophages. PMID- 4023634 TI - Difference in prevalence of hepatitis B markers in children born either in Sweden or in Turkey of Assyrian immigrants. AB - Sera from 95 children below 20 years of age born to Assyrian immigrants were tested for markers for hepatitis B virus (HBV). HBV markers were found in 26% of the study population. However, no markers were demonstrated in children born in Sweden. Of the 62 children born in Turkey or the Middle East 39% had HBV markers and 4 (6.5%) had HBsAg. Three of the 4 HBsAg+ children had anti-HBe and 1 HBeAg. These results suggest that the transmission of HB in Assyrians may be mainly horizontal rather than vertical. Children of Assyrian immigrants born in Sweden do not seem to constitute a risk group for transmission of HB, whereas those born in Turkey or the Middle East constitute the same risk as reported in a general population of Turks. PMID- 4023635 TI - Unfavourable prognostic factors in Staphylococcus aureus septicemia and endocarditis. AB - Factors predictive of a fatal outcome were retrospectively studied in 248 patients admitted with Staphylococcus aureus septicemia during 1965-1982, 78 of whom had endocarditis. 77 patients were intravenous drug addicts and 47 of them had endocarditis. 48 patients (19.4%) died. The fatality rate in addicts and non addicts from septicemia was 0% and 17.9% and from endocarditis 8.5% and 61.3%, respectively. After analyzing clinical and laboratory data available early in the course of the disease 4 risk factors were found both in septicemia and endocarditis: age greater than or equal to 60 yr, pre-existing cardiovascular disease, prior hospitalization within 30 days of onset of illness, and neurological symptoms and/or signs. In addition, in endocarditis a platelet count before therapy less than 100 X 10(9)/l and left-sided involvement were unfavourable prognostic factors. PMID- 4023636 TI - Neonatal pneumonia caused by Branhamella catarrhalis. AB - A 15-day-old, prematurely born male infant with bronchopneumonia caused by Branhamella catarrhalis is reported. One case of ophthalmia neonatorum was the only report found of B. catarrhalis infections in neonates when the literature was reviewed. PMID- 4023637 TI - Acute pancreatitis possibly caused by Legionella micdadei. AB - A case of acute haemorrhagic, ultimately fatal, pancreatitis in a 72-year-old man is presented. No pneumonia was found. High IgM-titres to Legionella micdadei were demonstrated. In addition 11 patients treated for pancreatitis were studied retrospectively. None had elevated titres to L. micdadei or L. pneumophila. PMID- 4023638 TI - Congenital nasal dermoid cysts and fistulas. AB - Eleven patients who underwent surgical excision of nasal dermoid cysts or fistulas are reported. The patients are discussed according to the aetiology, sex distribution, location on the nose, and possible inheritance. Our surgical results are satisfactory with only one case which required reoperation. We found that late diagnosed cysts had a higher frequency of deep involvement and therefore required more extensive surgery. PMID- 4023639 TI - Anatomical studies on the geometry and stability of the distal radio ulnar joint. AB - In fresh-frozen amputated- and cadaver arm specimens the anatomy and stability of the distal radio ulnar joint were investigated. The articulating surface of the sigmoid notch of the radius and the corresponding surface of the ulnar head facing the sigmoid notch were studied in transverse cryo sections. In each specimen the radius of the curvature of the sigmoid notch was 4-7 mm larger than that of the ulnar head and consequently pronation and supination are combined rotation-sliding movement in the distal radio ulnar joint. The radio ulnar ligament consists of a dorsal and a volar fibrous part, broadly attached to the distal rim of the sigmoid notch and converging towards the fovea of the ulnar head. The cartilaginous disc is centrally located between these fibrous strands. In neutral position the articulating surface of the sigmoid notch is optimally covering the articulating surface of the ulnar head. This contact area is gradually diminished during pronation-supination until only a marginal contact remains at the end of each movement. The distal radius is kept stable in pronation by the volar part and in supination by the dorsal part of the radio ulnar ligament. PMID- 4023640 TI - The distal radio ulnar joint. The influence of geometry and ligament on simulated Colles' fracture. An experimental study. AB - In five fresh frozen arm specimens Colles' fracture was simulated by a dorsal wedge osteotomy of the distal radius. A spring load was applied to the cortex of the distal radius fragment exerting a constant traction force in proximal direction. The distal radius fragment showed minimal dorsal angulation as the forearm was positioned in neutral or pronation, assuming the distal radio ulnar joint including its radio ulnar ligament was kept intact. As the forearm was moved into supination the distal fragment angulated dorsally to close the dorsal open gap in spite of the ligament being intact. When the radio ulnar ligament was detached the stability was however lost in any forearm position. The result supports the concept of immobilizing a satisfactorily reduced Colles' fracture in neutral position, possibly in slight pronation but never in supination. PMID- 4023641 TI - Experience with the latissimus dorsi flap. AB - A review of 65 applications of the latissimus dorsi flap based on the thoraco dorsal vessels to recipient sites in the head and neck area (10), on the torso (22), in the upper extremity (9) and in the lower extremity (24) in 62 patients with malignancies (28) and congenital deformities (6) is presented. Thirty-five flaps were transplanted with microsurgical vascular technique, while 30 flaps were pedicled. Vascular thrombosis at the anastomotic site was seen in 4/35 free tissue transplants and was successfully managed in 3 cases with an overall survival rate of 97% in this group, while all pedicled flaps survived. Healing complications including haematomas and wound infections were related to the nature of the recipient site and most commonly seen in the lower leg after resection of infected bone. In 3 cases leg amputations were performed within 6 months after the reconstruction, while 6 patients had secondary operations for tibial pseudoarthroses. Donor site morbidity was insignificant, without permanent, functional losses. It is concluded, that the thoracodorsal unit is a versatile and safe flap for reconstructive purposes. PMID- 4023642 TI - Late patency of clinical microvascular anastomoses to free composite tissue transplants. I. Angiographical aspects. AB - In a series of sixty-five free composite tissue transplantations by means of microsurgical techniques, 37 transplantations were performed to recipient sites in the lower extremity in 34 patients. Twenty-eight of these patients with 31 composite transplants were examined by femoral arteriography to assess the patency of 33 arterial anastomotic lines 6-45 months, median 12 months, postoperatively. Angiography showed patency in 32 of 33 arterial anastomotic lines, one arteriography being inconclusive. The results suggest that microsurgical techniques in small vessel anastomosis (ext. diam, 3/4-3 1/2 mm) are essential prerequisites for long-term vascular patency. PMID- 4023643 TI - Late patency of clinical microvascular anastomoses to free composite tissue transplants. II. Hemodynamical aspects. AB - In a series of 37 free composite tissue transplantations performed to the lower extremity in 34 patients, skin islands were included in 35 cases, as a cutaneous island flap (3), as a musculocutaneous island flap (19), and as an osteocutaneous island flap (13). In a follow-up study which included 26 patients with 29 flaps 6 48 months postoperatively an estimate was made of the importance of the blood supply through the vascular pedicle relative to the collateral blood supply through the recipient bed. Using transcutaneous oxygen tension measurements a significant reduction in calculated relative skin blood flow averaging 70% (p much less than 0.01) was seen after digital occlusion of the vascular stalk, suggesting that patent microvascular anastomoses are important for the vascularity of the transplanted tissues, not only for immediate postoperative survival, but also on the longer view. PMID- 4023644 TI - Bacteria in the female breast. AB - Subclinical infection may play a role in capsular formation around silicone breast implants. To assess the possibility of antibiotic prophylaxis for prevention of capsular formation, knowledge of bacteria present in the female breast tissue and the resistance pattern of these bacteria is needed. Samples were taken from 25 patients (49 breasts) peroperatively during reduction mammaplasty with an impression pad method. The samples were placed in agar plates and incubated both aerobically and anaerobically. In more than 90% of the samples bacteria were found. The species of bacteria found were mainly Staphylococcus epidermidis and propionibacteria. These bacteria were sensitive to penicillin G and/or isoxapenicillin. It remains to be shown that prophylactic antibiotic treatment will decrease capsular formation following augmentation mammaplasty. PMID- 4023645 TI - Renal stones--current viewpoints on etiology and management. PMID- 4023646 TI - Nonobstructive detrusor myopathy in a group of patients with chronic abacterial cystitis. AB - Chronic abacterial cystitis is clinically and pathoanatomically an ill-defined condition, presenting with a variety of urologic symptoms and often nonspecific histology. A retrospective histologic analysis of bladder biopsies from 101 patients with chronic abacterial cystitis revealed degenerative changes in the detrusor muscle cells (detrusor myopathy) in 25 of them. The changes were often very severe, and even fatty replacement of muscle tissue was seen. Retrospective analysis of the symptoms, urodynamics and cystoscopic findings in these patients showed that none had haematuria, but five (all women) had had urinary retention requiring catheterization. Significant residual urine was found in nine patients, and the cystometrograms showed a shift to the right. No patient had infravesical obstruction. At cystoscopy less than half of the patients had petechial bleeding after bladder distension. The aetiology and pathogenesis of the degenerative changes are unknown, despite theoretic speculation. The authors conclude that careful histologic examination can identify different clinical types of chronic abacterial cystitis. Such studies may assist future research into the nature of the problem and also the search for more rational therapy. PMID- 4023647 TI - Subcutaneous heparin in the treatment of interstitial cystitis. AB - Chronic interstitial cystitis (IC) is an inflammatory condition of the bladder of unknown aetiology. Clinically, IC is difficult to handle. Previously, we reported that administration of subcutaneous heparin has an immediate, ameliorating effect. We have now followed eight of the patients for one year or more, during which period they received subcutaneous heparin in doses varying from 5000 IU per day to 5000 IU 2-3 times a week. This treatment was found to have a long-term beneficial effect. No side effects were observed. PMID- 4023648 TI - Variations in upper urinary tract outflow resistance. The effect of high and low obstruction of ureter. AB - The upper urinary tract of the pig was subjected to acute standardized obstructions, size 10-F, 8-F and 6-F, in both the proximal and the distal part of the ureter. Each obstruction was followed by measurements of the renal pelvic pressure-flow relationship between 0 and 20 ml/ureter/min. The study showed that the mean baseline pressure in the renal pelvis changed due to the obstruction with an increase related to the degree of obstruction. When the flow was increased a pressure-flow relationship in essence similar to the normal pressure flow relationship was revealed. Thus phase 1, which is the pressure-flow relationship at low flow rate with urine flowing into a relaxed ureter, was practically eliminated and phase 2 was shifted to the left. The linear pressure flow relationship in phase 3 was preserved but there was tendency for higher increments with increasing degree of obstruction. Even in cases of severe obstruction both baseline measurements and perfusion pressure measurements showed results well within the normal accepted limits of renal pelvic pressure. It was furthermore shown that the overlap was smallest at the low flow rates between 0 and 2 ml/ureter/min. All degrees of distal obstruction had a lower pressure at flow rates below 10 ml/ureter/min than proximal obstruction, a pressure difference which could be attributed to the peristaltic activity of the ureter.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4023649 TI - Human umbilical vein for vascular access in chronic hemodialysis. AB - Since 1979 we have used human umbilical vein graft as the ultimate vascular access for hemodialysis in patients with chronic renal failure. In 24 patients 33 graft fistulas were performed. Several complications were encountered. Among these infection was the most serious, occurring in seven grafts. All these grafts were removed and never used for hemodialysis. Thrombosis occurred 25 times, and five grafts were lost because of this, whereas 20 grafts had successful thrombectomy and continued to function. Aneurysm formation occurred four times, two grafts were lost. Stenosis was seen in three cases, one graft was lost. In the material 26 grafts were used for hemodialysis and a median function time of 8.5 months was obtained. At the end of the observation period 10 grafts were open, eight were used for hemodialysis, two were not used because of successful transplantation. The umbilical vein graft is an acceptable alternative as vascular access where conventional methods of fistula formation have been exhausted. PMID- 4023650 TI - Secondary hyperparathyroidism in diabetic and nondiabetic patients on long-term continuous ambulatory peritoneal dialysis (CAPD). AB - Serum values of calcium, phosphate, alkaline phosphatases and parathyroid hormone (PTH) are reported for 24 diabetic and 26 nondiabetic patients treated with continuous ambulatory peritoneal dialysis (CAPD) for a total of 779 months, without the use of vitamin D or calcium supplements. Radiographic data are reported for 25 patients followed on CAPD for at least 12 months. Serum calcium was well maintained and control of hyperphosphataemia acceptable, but phosphate binding therapy had to be continued in the majority of patients. Diabetic patients had lower serum phosphate levels and higher serum calcium than nondiabetic patients during the first year of CAPD. In nondiabetic patients the institution of CAPD was followed by a fall in PTH, possibly largely reflecting transperitoneal PTH elimination. No patient achieved normalization of serum PTH on CAPD. Although no symptomatic bone disease was observed, radiographic evidence of progressive hyperparathyroid bone disease developed in 3 of the 25 examined patients, all nondiabetic. In summary, long-term CAPD with a dialysate calcium concentration of 1.75 mmol/l seems to be compatible with normocalcaemia and a steady-state situation with regard to secondary hyperparathyroidism in the majority of patients. Despite transperitoneal elimination, serum PTH remains elevated, and definite progression of hyperparathyroidism is observed in some patients, however, probably making a case for vitamin D therapy and/or intraperitoneal or peroral calcium supplementation in these patients. PMID- 4023651 TI - One-way obstruction during continuous ambulatory peritoneal dialysis (CAPD) with Tenckhoff catheter. Management by a simple operation. AB - Continuous ambulatory peritoneal dialysis (CAPD) is an important method of maintenance therapy for chronic uraemic patients. Dislodgement of the dialysis catheter and the consequent one-way obstruction is a serious complication that may indicate removal of the catheter altogether. We report here on a simple operation by which we have avoided catheter removal and thus interruption of CAPD. PMID- 4023653 TI - Transsphincteric-transrectal repair of posttraumatic urethrorectal fistula. Case report. AB - The York Mason transsphincteric-transrectal approach for closing postoperative rectoprostatic fistulas was used in a case of posttraumatic urethrorectal fistula 32 years after original trauma. This is the first report of the application of this method to urethral trauma complicated by urethrorectal fistula. PMID- 4023652 TI - Direct inhibitory effects of natural and synthetic oestrogens on testosterone release from human testicular tissue in vitro. AB - Human testicular slices were incubated in vitro in order to examine the direct effects of natural and synthetic oestrogens on testosterone secretion. In the presence of human chorionic gonadotrophin (10 IU per ml), oestradiol-17 beta (1 or 10 micrograms per ml) and ethinyl oestradiol (0.1, 1 or 10 micrograms per ml) inhibited testosterone release into the media in a dose dependent manner. The addition of estramustine phosphate, estromustine, diethylstilboestrol or diethylstilboestrol diphosphate in comparable concentrations produced no significant effects on testosterone release. PMID- 4023654 TI - Spontaneous scrotal emphysema--a cause of scrotal swelling. AB - Scrotal emphysema developed in a 24-year-old man without any sign of infection and without any trauma involved. The condition gradually improved over a few days and at follow-up one week later he was back to his normal state. No clue to the cause was found and it is therefore justifiable to claim that the patient has a 'spontaneous scrotal emphysema'. PMID- 4023655 TI - [Chlorinated hydrocarbons in the environment I. Trichloroethylene, perchloroethylene, 1,1-dichloroethylene, 1,2-dichloroethylene]. PMID- 4023656 TI - Perceptgenetic defenses against anxiety and a threatened sense of self as seen in terms of the Spiral Aftereffect Technique. PMID- 4023657 TI - The effect of stimulus preexposure upon the context effect in taste-aversion learning in noradrenaline-depleted rats. PMID- 4023658 TI - Neuropsychological cognitive performance of patients with type-2 diabetes. AB - The aim of this study was to assess the cognitive skills and visuo-motor performances of patients with type-2 diabetes. An ADL questionnaire, neurophysiological EEG recordings and a comprehensive battery of neuropsychological tests were administered to 33 type-2 diabetics and to 33 matched controls. Neither neuropsychological nor neurophysiological EEG findings differentiated type-2 diabetics as a group from their controls. PMID- 4023659 TI - Isokinetic plantar flexion endurance. Reliability and validity of output/excitation measurements. AB - The reliability and validity of isokinetic measurement of plantar flexion endurance has been studied by a method previously described by us which utilizes simultaneous measurements of mechanical contractional work (CW) and integrated electromyogram (iEMG). The reliability was gauged by test/re-test with a two year's interval; while validity was assessed by myoelectric power spectrum analyses. The output/input balance (CW/iEMG) remained unchanged for the group as well as inter-individually. Changes in myoelectric power spectrum as function of number of contractions were clearly indicative of fatigue. Under the present conditions fatigue of fast twitch motor units may explain the rapid decreases in output and excitation followed by nearly steady state levels of all registered parameters. As is the case for non-fatigued isokinetic plantar flexions, the motor unit recruitment order appears quite stereotyped during plantar flexion fatigue. The findings of significantly lower mean power spectrum during the first part of each contraction than during the second part may support the size principle described by Henneman. PMID- 4023660 TI - Muscular activity during ergometer cycling. AB - The aim of the study was to quantify the activity as recorded by electromyography during ergometer cycling in eleven different muscles of the lower extremity. Eleven healthy subjects rode in twelve different ways at different work-load, pedalling rate, saddle height and pedal foot position. Vastus medialis and lateralis, gastrocnemius medialis and lateralis and the soleus muscle were the most activated muscles. Changes in muscle activity during different calibrations were studied in eight of the eleven muscles. An increase in work-load significantly increased the mean maximum activity in all the eight muscles investigated. An increase of the pedalling rate increased the activity in the gluteus maximus, gluteus medius, vastus medialis, medial hamstring, gastrocnemius medialis and soleus muscles. An increase of the saddle height increased the muscle activity in the gluteus medius, medial hamstring and gastrocnemius medialis muscles. Use of a posterior pedal foot position increased the activity in the gluteus medius and rectus femoris muscles, and decreased the activity in the soleus muscle. PMID- 4023661 TI - Patellar forces during knee extension. AB - A radiographical study of 20 loaded knees of healthy subjects and a knee dissection study of 20 specimens were performed in order to present a two dimensional patello-femoral joint biomechanical model. A constant knee-extending moment gave 25-40% lower force magnitudes in the patellar tendon than in the quadriceps tendon if the knee was flexed to 60-120 deg. The magnitude of the patello-femoral joint compressive force reached its maximum at 90 deg knee angle and decreased slightly towards 120 deg. A compressive force between quadriceps tendon and femoral intercondylar groove was present above 60 deg knee angle and its magnitude was estimated. The patellar forces in women were about 20% higher than in men. The biomechanical model may be used in knee rehabilitation activities to optimize and individualize exercise programmes. The model may also be applied to daily activities in order to quantify patellar forces. PMID- 4023662 TI - Acquiring and maintaining self-care skills after stroke. The predictive value of apraxia. AB - The degree of self-care in 120 patients who had suffered unilateral cerebrovascular accident (CVA) was assessed at different stages of recovery. The level of ADL (activities of daily living) function was determined on admission and discharge. Patients with right-sided hemiplegia (r. hem.) were given a set of apraxia tests on admission to the hospital. The results of ADL evaluation showed improved ADL function between admission and discharge, but a worsening after returning home. There were some significant relationships between ADL function in hospital and apraxia. All the apraxia variables are significant as predictors of subsequent dependency. The results show the seriousness of problems related to apraxia in rehabilitation of stroke patients with a lesion in the left hemisphere. One conclusion is that the treatment procedure ought to be directed to the various symptoms of apraxia. The effect of apraxia on ADL in the domestic situation has to be given more attention. More treatment should be given in the home, as patients seem to have difficulty in transferring the skills learned in hospital to the home situation and in maintaining them. PMID- 4023663 TI - The local skin blood flow in areas at risk for pressure sores treated with massage. AB - In order to evaluate methods to prevent pressure sores the effect of massage on the local skin blood flow was studied in normal skin and in skin with discolouration (red or reddish blue). In this study massage is defined as small circular movements with the fingertips using liniment. The cutaneous blood flow was measured with a laser Doppler flowmeter. To study the long term effect of massage on normal skin ten patients were measured over a twenty day period with five days before and after a ten day period with massage. Twenty-nine patients with cerebral haemorrhage were measured for two days each to examine the effect immediately after the massage on normal skin. Fifteen patients with discolouration were measured for one day each both on normal skin and injured skin. The difference in blood flow before and after the ten day period of massage was inconsistent and insignificant. The effect of massage which appeared one to two minutes after the stimulus was implemented varies between individuals and within individuals; significantly more women than men increased their skin blood flow bilaterally after massage. In the centre of the injured skin the basal blood flow was higher than in normal skin and it decreased after the massage was implemented. The results stress the importance of continued research to provide an opportunity for individualization in the selection of methods to prevent and treat pressure sores. PMID- 4023664 TI - Impact of a health education program and other factors on stopping smoking after heart attack. AB - A prospective follow-up study was carried out to investigate the impact of a health education program and other factors related to patient's social background and severity of heart attack on stopping smoking after heart attack. The study consisted of male patients below the age of 65 years, who had suffered a heart attack between April 1 and September 30, 1977, living in two provinces of eastern Finland, North Karelia and Kuopio. Of the patients who smoked before the heart attack, 102 responded to both the 6- and the 12-month follow-up postal survey. Of these 102 patients, 25 stopped smoking within 12 months after the heart attack, while 77 continued to smoke. Continuing smoking was most strongly associated with working and unemployment before heart attack, maximum serum aspartate aminotransferase (GOT) concentration and subjective recovery after the heart attack. The quitting rate among men in the program area was 1.2-fold (p = 0.012) compared with the reference area men, after making allowance for the seven most confounding factors in the multivariate analysis. This observation indicates that either the community-based primary program or the secondary prevention program in North Karelia succeeded in dissuading patients from smoking after heart attack. PMID- 4023666 TI - Future challenges to health services. PMID- 4023665 TI - Health status and social conditions of the elderly in remote districts. Results of a screening programme. AB - In 1978 a cohort of 1040 individuals aged 65 years or over was screened by public health nurses in Kuusamo. The screening produced basic data about health status and social conditions for an intervention of active medical care of the elderly by means of a mobile unit in rural districts. The response rate of the screening was 90%. 72% of the men and 35% of the women lived with their spouse; 6% of the men and 20% of the women lived alone. Poor health was assessed least commonly (36%) by those living alone, and most commonly by women living with their spouse (51%), even though 87% of them were under 75 years old. A visit to a physician during the past 12 months was more common among younger subjects. 15% of the men and 18% of the women had slightly restricted mobility. Men living alone had better mobility than women living alone. PMID- 4023667 TI - Life-threatening torture without visible marks. PMID- 4023668 TI - Psychological and physical long-term effects of torture. A follow-up examination of 22 Greek persons exposed to torture 1967-1974. AB - After an observation period of about 10 years a follow-up examination was made of 22 Greeks earlier exposed to torture. All had physical symptoms and about 90% of the examinees had chronic psychological symptoms which had appeared after the torture experience, the most notable of which were emotional instability, depression, passivity, fatigue and disturbed sleep. Eight of the victims had a chronic organic psychosyndrome as defined by us. The clinical picture of the torture victims is very similar to other stress-conditioned syndromes, which underlines the significance of the psychological trauma for the pathogenesis. Certain physical symptoms can be related to specific forms of torture; in this series particularly, symptoms of the feet and lower extremities can be related to 'falanga' (repeated blows to the soles of the feet). The most noticeable objective finding was unilateral atrophy of testis in 2 of the examinees caused in all probability by genital torture. Treatment of the sequelae to torture should be initiated as early as possible in the course of the illness, and studies on the effect of this treatment should be carried out. PMID- 4023669 TI - Lower limb fractures and registration for alcoholism. AB - During two consecutive years 607 individuals with lower limb fractures were diagnosed. Half of the individuals, 315, were women and only 14 of them had an earlier registration for alcoholism. In the 292 men, however, 73 men or 25%, had been registered at the Department of Alcohol Diseases at least once during the 13 years of observation, the highest registration frequency (30%) was noted in the malleolar fractures in men. In males, 30-50 years of age, there were 37 per cent who had a registration for alcoholism, the highest registration (44%) was noted for fracture of the tibial diaphysis. Males with fracture of the proximal end of the femur between 16-80 years of age were registered for alcoholism in 23%. PMID- 4023670 TI - [Chronic pulmonary hypertension of vascular origin, plexogenic pulmonary arteriopathy and the appetite depressant aminorex: addenda to an epidemic]. AB - An epidemic of chronic pulmonary hypertension occurred in Austria, the Federal Republic of Germany, and Switzerland, starting in 1967, peaking in 1968/69, and disappearing after 1972. The mechanism leading to pulmonary hypertension was precapillary vascular obstruction due to plexogenic pulmonary arteriopathy. There was a close geographic and temporal relationship between the epidemic and the marketing and intake of the appetite-depressing drug aminorex fumarate (Menocil). The epidemic was limited to the three above countries where aminorex had been on sale. In the individual patient the symptoms, usually dyspnea, angina pectoris and syncope on exertion, used to follow the beginning of the drug in-take after one year. A similar phase shift could be observed between marketing of the anoretic and the incidence of patients with chronic pulmonary hypertension of vascular origin. The new disease is compared with known forms of pulmonary vascular obstruction. It cannot be distinguished from classical primary pulmonary hypertension or from recurrent silent pulmonary thromboembolism on either clinical or functional grounds; it has plexogenic pulmonary arteriography in common with the former. The prognosis, however, is different: survival is considerably longer in patients with aminorex-associated pulmonary hypertension, and a marked decrease in the pulmonary vascular obstruction after 10 years is no exception. Considering the closeness of the various associations between the event (i.e. the epidemic) and its suspected cause (the anoretic aminorex) from the viewpoint of epidemiological, pharmacological, morphological and prognostic findings and considerations, there is little doubt that aminorex, besides other partly known and partly unknown factors, can in fact favour or cause the development of plexogenic pulmonary arteriography and pulmonary hypertension.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4023671 TI - [Decompression sickness of the spinal cord. Results of early and of late treatment]. AB - The treatment of 20 scuba divers with decompression sickness of the spinal cord between 1969 and 1984 is reported. Seven patients presented with mild sensomotor impairments, 13 patients were paraplegic and some suffered from additional impairments to the arms. In 12 of the divers the accident that occurred in a Swiss lake and recompression was initiated with a latency of a few hours. These early treatments were successful in 11 patients. The neurologic symptoms already improved during recompression even in the 7 patients who were paraplegic. In a paraplegic woman early treatment failed, but her condition improved under subsequent hyperbaric oxygen treatment. In 9 patients late treatment after an interval of 48 to 192 hours, consisting of repeated hyperbaric oxygen exposures, was performed. 3 patients with mild neurologic disturbances improved completely. 6 patients were paraplegic. In 5 of these early treatment was without success. On 3 occasions, however, early treatment was not started before 15 to 24 hours after the dive. All 6 paraplegic patients improved considerably during late treatment. 8 of the 9 patients undergoing hyperbaric oxygen treatment had been transported by air with slightly reduced cabin pressure from the foreign country to Zurich. No deterioration of neurologic symptoms was observed during air transport. PMID- 4023672 TI - [Stomach rupture while diving]. AB - A case of stomach rupture in a 47-year-old scuba diver is reported. Symptoms of gastrointestinal expansion during ascent are quite common and are caused by decompression of swallowed air. Gastric perforation is however rare, and needs to be promptly recognized and surgically repaired. PMID- 4023673 TI - [Prolactin producing hypophyseal adenoma: diagnosis and therapeutic possibilities]. AB - The introduction of radioimmunoassay for prolactin concentrated interest in infertility research on prolactin-producing pituitary adenomas (prolactinomas). In women in the fertile age group these tumors cause amenorrhea and galactorrhea, and in men loss of libido, impotence and occasionally gynecomastia. Microprolactinomas (diameter 10 mm and less) and macroprolactinomas (diameter more than 10 mm) differ in growth characteristics, symptomatology and prognosis. Different therapeutic approaches may be used. Both bromocriptine treatment and selective microsurgical tumor extirpation are successful. Both have advantages and disadvantages, thus rendering the decision as to appropriate treatment increasingly difficult. Recent findings demonstrate that bromocriptine may cause irreversible tumor fibrosis, which decreases the chances of prolactin normalization by subsequent surgery. PMID- 4023675 TI - [Pre-exposure rabies vaccination using a new duck embryo vaccine]. AB - An economical, highly purified and concentrated duck embryo rabies vaccine (PDEV) was investigated in relation to pre-exposure rabies prophylaxis. The vaccine was injected subcutaneously according to the then prescribed scheme for human diploid cell rabies vaccines (HDCV). Additionally, a third dose was given on day 120. Serum anti-rabies antibody levels were determined on days 0, 56, 120, und 170. On day 56 all volunteers showed an anti-rabies antibody level of at least 1.0 IU/ml, indicating that PDEV is sufficiently immunogenic to allow its use according to the pre-exposure schedules for HDCV. Some rather low titers noted on day 120 indicate that an early booster dose or a third primary immunization dose is justified, as recently recommended by the WHO. PMID- 4023674 TI - [Correlation between endoscopy and histology of 48 cases of superficial stomach cancer]. AB - The relationship between different endoscopic (gross appearance, diameter, localization, morphological type according to the Japanese Endoscopic Society) and histological parameters (type of cancer according to Lauren, tumor infiltration, association with metaplastic chronic gastritis) were analyzed retrospectively in 48 patients operated on for early gastric cancer. Endoscopy and histology provided a preoperative diagnosis of malignancy in 89.6% of the cases. With endoscopy alone the results were 23% malignancy, 44% suspicious and 33 benign. The antrum was the preferential site and type III the most frequent form. 62% of early gastric cancers were of the intestinal type and the average age of the patients was higher than for the diffuse type. Metaplastic chronic gastritis was associated in 67% of the intestinal type and in 21.5% of the infiltrating type. The degree of tumor infiltration was related to the diameter of the lesion, irrespective of the histological type. Since a malignant or suspicious lesion was diagnosed in only 67% by endoscopy alone, it is imperative to perform several biopsies of all gastric lesions, including even the smallest: 11 cancers of type III and IIc in this series had a diameter inferior to 1 cm and had been classified endoscopically as benign. PMID- 4023676 TI - [Poisoning by domestic vipers (Vipera berus and Vipera aspis). A retrospective study of 113 patients]. AB - In a retrospective study, 113 bites which occurred in Switzerland within a 16 year period by either of the two indigenous adders (Vipera berus and Vipera aspis) were analyzed. 13 patients showed no signs of envenomation. Out of the other 100, 62 patients had merely minor (local edema only) and 24 moderate envenomation (vomiting, diarrhea, cramps, hypotension), while 24 had severe envenomation (shock and angioneurotic edema of the tongue and lips). No fatalities were recorded. In residents of the endemic area the bites occurred accidentally in 86% of the cases, while tourists were bitten after manipulating the snake in 42%. Specific antivenin was given to 49 of 95 hospitalized patients. In cases of severe envenomation (n = 14) a reduction of the median duration of hospitalization from 10 days in patients without antivenin therapy (n = 4) to 5 days in patients with antivenin therapy (n = 10) was obtained. In cases of moderate (n = 21) or minor envenomation (n = 49), antivenin therapy did not influence the hospital stay of 4 and 2 days respectively. In the 11 patients with bites not followed by envenomation the antivenin treatment increased the duration of hospitalization from 1 day (in 6 patients without antivenin) to 2 days (in 5 patients with antivenin). Side effects of the antivenin treatment, such as urticaria, angioneurotic edema, respiratory distress, fever and lymphadenopathy were noted in 4 out of 49 patients. PMID- 4023677 TI - [Sticks and diagnostic strips in urine diagnosis]. PMID- 4023678 TI - [Multidisciplinary study of the prolonged treatment of involution osteoporosis using sodium fluoride with calcium, phosphate and vitamin D]. AB - A multidisciplinary study on the prolonged treatment of involution osteoporosis with fluoride was performed on a homogeneous population of 31 women aged 51 to 75 years (mean 64 years). The selection criteria were the following: significant backache, vertebral compression fractures on X-rays, bone biopsy evidence of osteoporosis, and absence of other risk factors after a complete workup. The patients were treated for a period of 3 to 6 years (mean 4 years) with daily doses of 30 mg (10 mg 3 times) fluorides ion associated during the last 3 years with 500 mg calcium twice daily, 750 mg phosphate and 1000 units vitamin D daily. The study demonstrated a favourable effect of the treatment on the backache and that it was well tolerated in the majority of cases, the side effects being intermittent osteo-articular pains of the lower extremities due to the fluoride in 9 patients, and gastric intolerance to the phosphate in 7. X-ray follow-up showed slowing of the vertebral compressions after the first year of treatment, but no effect on fractures of the extremities. There was no evidence of alterations in parameters of mineral and bone metabolism, and in endocrine, hepatic, renal or hematological assays. Histomorphometric and biophysical examination of biopsies indicated that, although there was no significant increase in the quantity of mineralized bone under the treatment, there was a very significant improvement in the crystallinity of the mineral substance, thus enhancing the quality of the bone tissue and its resistance to pressure. This study is the first in which a catamnesis of the patients was undertaken, 28 of them having received a clinical and radiological examination 2 years after the end of therapy: a favourable evolution was observed in most of the cases, both in those patients treated for a period of 3 years and in those whose treatment had lasted for a longer period. PMID- 4023679 TI - [The significance of distal obstructions and stenoses of the vertebral artery]. AB - 3 patients with intracranial infarctions as consequence of obstructive lesions of the distal vertebral artery are presented. The first patient, with a unilateral occlusion of the distal intracranial portion of the vertebral artery and contralateral high grade stenosis at the same site, suffered bilateral cerebellar infarctions. Predominantly occipital infarction occurred in the second patient, with unilateral occlusion of the vertebral artery, the infarction being probably caused by embolization from the distal stump. In the third patient traumatic injury of the vertebral artery at the C1/C2 level was followed by embolic occipital lobe infarction. The discussion covers pathogenetic significance of hemodynamic and thromboembolic factors for cerebellar and occipital infarctions and the possible therapeutic options. PMID- 4023680 TI - [Transcutaneous bilirubin determination: correlation in white premature infants weighing less than 1500 gm]. AB - The transcutaneous bilirubinometer (TcB) was evaluated in 24 preterm infants of less than 34 weeks gestation and weight less than 1500 g. A close correlation between the TcB index and serum bilirubin values was obtained with 50 measurements at sternum (R = 0.858, p less than 0.001). From these resultant ratios it is concluded that the TcB-meter is a valuable tool in screening healthy preterm infants less than 34 weeks gestation for hyperbilirubinemia. PMID- 4023681 TI - [Medical problems in refugees from Sri Lanka (Tamil)]. PMID- 4023682 TI - [Game animals in the current cultural environment]. PMID- 4023683 TI - [A case of accidental arsenic poisoning in cattle with special reference to the evaluation of histopathological lesions]. PMID- 4023684 TI - [Clinicochemical parameters in the Camargue horse]. PMID- 4023685 TI - [Helminthic pneumonia in fattening swine]. PMID- 4023686 TI - [Cardiovascular study of the horse: relation between vascular and tissue changes in the myocardium. 3]. PMID- 4023687 TI - [Colitis X in the horse: 9 cases]. PMID- 4023689 TI - [Intestinal polyps in small ruminants with chronic coccidiosis]. PMID- 4023688 TI - [Acute pullorum disease in hawk-headed parrots (Deroptyus accipitrinus fuscifrons)]. PMID- 4023690 TI - [The uncertainty of "accuracy". On the reliability of a variably employed concept]. AB - A diagnostic "striking accuracy" causes more inaccuracy than accuracy. Undefined terms like this are nearly worthless because they are used differently in the literature and cannot be compared. To compare the results of diagnostic studies scientifically it is necessary to use defined terms. PMID- 4023691 TI - [Chronic cor pulmonale from the echocardiographic viewpoint]. AB - The morphologic changes of the right heart occurring in chronic cor pulmonale can be detected by means of twodimensional echocardiography. Chronic cor pulmonale can be classified according to semiquantitative echocardiographic criteria using a subcostal window: Stage I: enddiastolic free right ventricular anterior wall greater than 5 mm, the right heart smaller than the left, vena cava inferior less than 10 mm/m2 body surface area, inspiratory collapse greater than or equal to 50%. Stage II: enddiastolic free right ventricular anterior wall greater than 5 mm, the right ventricle in comparison with the left eccentrically enlarged, vena cava inferior like Stage I. Stage III: free right ventricular anterior wall cannot be measured, the right heart in comparison with the left markedly enlarged, vena cava inferior greater than 10 mm/m2 body surface area, inspiratory collapse less than 50%. PMID- 4023692 TI - A study of dynamic development in radiolesion and cell death of eukaryotes after exposure to ionizing radiation--the visualization of the dynamic reaction by means of cytochemical method with lactate dehydrogenase (LDH) as a nuclear marker and radiation-induced nuclear anomalization by an ultramicrostructural manifestation: a dynamic explanation. AB - The present work deals with the radiation effect on adult rats suffering from acute, whole-body irradiation with cobalt-60 gamma rays of dosages 100R and 300R respectively. The morphological alteration of the lymphocytic nucleus and exhibition of cytochemical reaction of LDH in intra- or extra-nuclear region has been observed at the end of predetermined time intervals after irradiation. A close relationship between the percentage of damage of the lymphocytic nucleus and that of positivity of LDH reaction is seen from their variations with time parallel. From technical color microphotographs which exhibit cytochemical reactions, the existence of enzyme LDH in the nucleus so far obscure has been visually recognized. The events happening in enzymic reaction and the leakage of enzyme across the nuclear envelope reflect the dynamic nature. The ultrastructural alteration of nuclear anomalization confirms the dynamic development of inducing radiolesion. The experimental facts inspire us to attempt an explanation of cellular radiolesion and cell death owing to ionization radiation in light of the dynamic concept. PMID- 4023693 TI - Triplicated alpha-globin gene loci in a Chinese family. AB - Utilizing restriction endonuclease mapping and blot hybridization, we have determined the arrangement of the alpha-globin genes in a Chinese family. The father and mother had no obvious alpha-thalassemia symptoms, but their twin daughters suffered from HbH disease. The gene analysis showed that the mother had three alpha-globin genes in one chromosome and no alpha-globin gene in the other (alpha alpha alpha/--), the father was a heterozygote of alpha-thal2 (alpha alpha/-alpha). Their twin daughters were double heterozygotes of alpha-thall and the rightward deletion genotype alpha-tha12 (--/-alpha). PMID- 4023694 TI - Levels of heavy metals in the tidal Elbe and its estuary and the heavy metal input into the sea. AB - Surface water samples were collected during missions in 1977, 1978, 1980 and 1983 at different sampling stations along the tidal Elbe, from river km 632 downstream from Hamburg to the outer end of the estuary. Special care was taken to minimize contamination during sampling, handling and analysis. Within the tidal Elbe five distinct zones of substantial anthropogenic heavy metal pollution inputs can be detected. An attempt is made to define anthropogenic background levels, which are extremely low for the dissolved trace metals Cd and Pb; 35 and 65 ng/kg, respectively. The level of dissolved Cu is 2200 ng/kg. Total baseline levels of Cd, Pb and Cu are, respectively, 120, 2500 and 4200 ng/kg. In the five river zones affected by anthropogenic trace metal inputs, distinctly larger maximum levels can occur. They decrease to the background values after mixing with the main water body. More elevated levels caused by re-suspension in the mixing zone with maximum turbidity can be assumed. Nickel and Co data are from one mission only. The order of magnitude of the trace metal input from the Elbe into the sea is evaluated. PMID- 4023695 TI - Man's mercury loading from a dental amalgam. AB - The release of mercury from an amalgam surface in natural saliva during cyclic loading, as well as under static conditions, simulating the clinical conditions of chewing and rest, has been studied using a nuclear tracer technique. Cyclic loading strongly promoted degradation of the amalgam surface in the saliva environment. Corrosion products were found to be loosely bound on the amalgam surface and could be removed by brushing similar to toothbrushing. Most of the mercury released from the surface was present in amalgam particles, produced during the cyclic loading procedure. The daily release of ionic mercury was estimated to be approximately 3 micrograms/cm2, according to the model experiment. Extrapolating the present findings to clinical conditions, man's ionic mercury intake from dental restorations may be at the same level as the total mercury intake from food and drink. PMID- 4023696 TI - Lead in playground dust and on the hands of schoolchildren. AB - Measurements of the quantity of lead on the hands of schoolchildren and of the concentration of lead in dust from school playgrounds have been carried out; the hand-lead was collected by wiping with a moist tissue. When hand-lead and dust lead values were averaged for each school, a statistically significant relationship between the two sets of means was obtained. Some limited measurements of size distribution of the dust particles on the children's wipes were also made; these indicated that most of the particles were less than 10 micron in diameter. PMID- 4023697 TI - The development and application of empirical models for the high SO2 concentration in urban areas. AB - The development of empirical models to describe extreme values of SO2 concentration directly from data collected over a 10-year period is described. A graphical method for the rapid calculation of high and maximum SO2 concentrations from the arithmetic mean of the concentrations recorded during the sampling period is reported. Applications of the resulting empirical models to the control of air quality and the planning and reduction of SO2 source emissions are illustrated. These applications are currently being developed by the Air Quality Control Authority of the Milan Area. PMID- 4023698 TI - The structure of arthropod hemocyanins. AB - Hemocyanins are large multi-subunit copper proteins that transport oxygen in many arthropods and molluscs. Comparison of the amino acid sequence data for seven different subunits of arthropod hemocyanins from crustaceans and chelicerates shows many highly conserved residues and extensive regions of near identity. This correspondence can be matched closely with the three domain structure established by x-ray crystallography for spiny lobster hemocyanin. The degree of identity is particularly striking in the second domain of the subunit that contains the six histidines which ligate the two oxygen-binding copper atoms. The polypeptide architecture of spiny lobster hemocyanin appears to be the same in all arthropods. This structure must therefore be at least as old as the estimated time of divergence of crustaceans and chelicerates, about 540 to 600 million years ago. PMID- 4023699 TI - Is the war on cancer being won? PMID- 4023700 TI - Seal lungs collapse during free diving: evidence from arterial nitrogen tensions. AB - Arterial blood nitrogen tensions of free-diving Weddell seals (Leptonychotes weddelli) were measured by attaching a microprocessor-controlled blood pump and drawing samples at depth to determine how these marine mammals dive to great depths and ascend rapidly without developing decompression sickness. Forty-seven samples of arterial blood were obtained from four Weddell seals during free dives lasting up to 23 minutes to depths of 230 meters beneath the sea ice of McMurdo Sound, Antarctica. Peak arterial blood nitrogen tensions of between 2000 and 2500 millimeters of mercury were recorded at depths of 40 to 80 meters during descent, indicating that the seal's lung collapses by 25 to 50 meters. Then arterial blood nitrogen tensions slowly decreased to about 1500 millimeters of mercury at the surface. In a single dive, alveolar collapse and redistribution of blood nitrogen allow the seal to avoid nitrogen narcosis and decompression sickness. PMID- 4023702 TI - Johns Hopkins drops MCAT requirement. PMID- 4023701 TI - The structure of a T = 1 icosahedral empty particle from southern bean mosaic virus. AB - The structure of a T = 1 icosahedral particle (where T is the triangulation number), assembled from southern bean mosaic virus coat protein fragments that lacked the amino-terminal arm, was solved by means of model building procedures with the use of 6-angstrom resolution x-ray diffraction data. The icosahedral five-, three-, and twofold contacts were found to be similar, at this resolution, to the analogous contacts (icosahedral five-, quasi-three-, and quasi-twofolds) found in the parent T = 3 southern bean mosaic virus. However, the icosahedral fivefold contacts of the T = 3 structure are the most conserved in the T = 1 capsid. These results are consistent with a mechanism in which pentameric caps of dimers are the building blocks for the assembly of T = 1 and T = 3 icosahedral viruses. PMID- 4023703 TI - Debate over colon cancer screening. PMID- 4023704 TI - Picosecond time-resolved resonance Raman studies of hemoglobin: implications for reactivity. AB - Picosecond time-resolved Raman spectra of hemoglobin generated with blue pulses (20 to 30 picoseconds) that were resonant with the Soret band and of sufficient intensity to completely photodissociate the starting liganded sample are reported. For both R- and T-state liganded hemoglobins, the peak frequencies in the spectrum of the deoxy transient were the same at approximately 25 picoseconds as those observed at 10 nanoseconds subsequent to photodissociation. In particular, the large R-T differences in the frequency of the stretching mode for the iron-proximal histidine bond (VFe-His) detected in previously reported nanosecond-resolved spectra were also evident in the picosecond-resolved spectra. The implications of this finding with respect to the distribution of strain energy in the liganded protein and the origin of the time course for geminate recombination are discussed. On the basis of these results, a microscopic model is proposed in which delocalization of strain energy is strongly coupled to the coordinate of the iron. The model is used to explain the origin of the R-T differences in the rates of ligand dissociation. PMID- 4023705 TI - The brain connection: the corpus callosum is larger in left-handers. AB - The size of the midsagittal area of the human corpus callosum obtained from postmortem measurement varied with tested hand preference. The corpus callosum, the main fiber tract connecting the two cerebral hemispheres, was larger by about 0.75 square centimeter, or 11 percent, in left-handed and ambidextrous people than in those with consistent right-hand preference. The difference was present in both the anterior and posterior halves, but not in the region of the splenium itself. This callosal morphology, which varied with hand preference, may also be related to individual differences in the pattern of hemispheric functional specialization. The greater bihemispheric representation of cognitive functions in left- and mixed-handers may be associated with greater anatomical connection between the hemispheres. The naturally occurring regressive events in neurogenesis, such as neuronal cell death and axonal elimination, may be factors in the individual differences in brain morphology and in functional lateralization. Specifically, right-handers may be those with more extensive early elimination of neural components. PMID- 4023706 TI - Androgens prevent normally occurring cell death in a sexually dimorphic spinal nucleus. AB - The spinal nucleus of the bulbocavernosus (SNB) contains many more motoneurons in adult male rats than in females. Androgens establish this sex difference during a critical perinatal period, which coincides with normally occurring cell death in the SNB region. Sex differences in SNB motoneuron number arise primarily because motoneuron loss is greater in females than in males during the early postnatal period. Perinatal androgen treatment in females attenuates cell death in the SNB region, reducing motoneuron loss to levels typical of males. The results suggest that steroid hormones determine sex differences in neuron number by regulating normally occurring cell death and that the timing of this cell death may therefore define critical periods for steroid effects on neuron number. PMID- 4023707 TI - Nucleotide sequence of yellow fever virus: implications for flavivirus gene expression and evolution. AB - The sequence of the entire RNA genome of the type flavivirus, yellow fever virus, has been obtained. Inspection of this sequence reveals a single long open reading frame of 10,233 nucleotides, which could encode a polypeptide of 3411 amino acids. The structural proteins are found within the amino-terminal 780 residues of this polyprotein; the remainder of the open reading frame consists of nonstructural viral polypeptides. This genome organization implies that mature viral proteins are produced by posttranslational cleavage of a polyprotein precursor and has implications for flavivirus RNA replication and for the evolutionary relation of this virus family to other RNA viruses. PMID- 4023709 TI - The neglected disease in medical education. PMID- 4023708 TI - Food dyes fuel debate over Delaney. PMID- 4023710 TI - Antibody-directed urokinase: a specific fibrinolytic agent. AB - A specific fibrinolytic agent was synthesized by covalently coupling urokinase to a monoclonal antibody that was fibrin-specific and did not cross-react with fibrinogen. The antibody was raised against a synthetic peptide representing the seven amino-terminal residues of the beta chain of human fibrin. The urokinase antifibrin conjugate retained the original binding specificity of the antibody and showed 100-fold increased fibrinolysis in vitro when compared to unmodified urokinase. The presence of human fibrinogen at plasma concentration did not influence these properties. PMID- 4023711 TI - Noninvasive study of high-energy phosphate metabolism in human heart by depth resolved 31P NMR spectroscopy. AB - Phosphorus-31 nuclear magnetic resonance (NMR) spectra showing the relative concentrations of high-energy phosphate metabolites have been recorded noninvasively from the human heart in vivo. Spectral data were spatially localized by combining a pulsed magnetic field gradient with surface NMR excitation-detection coils. The location of the selected spectral region was determined by conventional proton NMR imaging immediately before examination by phosphorus-31 NMR spectroscopy. PMID- 4023712 TI - Diversity of circumsporozoite antigen genes from two strains of the malarial parasite Plasmodium knowlesi. AB - The complete nucleotide sequence of the coding region of the circumsporozoite antigen gene (CS gene) of the Nuri strain of the malarial parasite Plasmodium knowlesi is presented. The gene from the Nuri strain exhibits a novel form of sequence diversity when compared to the CS gene from the H strain. Instead of the 12 tandem repeating 36-base pair units of the H strain, the Nuri strain contains 16 tandem repeating 27-base pair units of a different nucleotide sequence that encodes a different repeating peptide. In contrast, the 5' and 3' coding and noncoding sequences flanking the repeats are 98 percent conserved in both strains. PMID- 4023713 TI - Selective attention gates visual processing in the extrastriate cortex. AB - Single cells were recorded in the visual cortex of monkeys trained to attend to stimuli at one location in the visual field and ignore stimuli at another. When both locations were within the receptive field of a cell in prestriate area V4 or the inferior temporal cortex, the response to the unattended stimulus was dramatically reduced. Cells in the striate cortex were unaffected by attention. The filtering of irrelevant information from the receptive fields of extrastriate neurons may underlie the ability to identify and remember the properties of a particular object out of the many that may be represented on the retina. PMID- 4023714 TI - Hydrophobicity of amino acid residues in globular proteins. AB - During biosynthesis, a globular protein folds into a tight particle with an interior core that is shielded from the surrounding solvent. The hydrophobic effect is thought to play a key role in mediating this process: nonpolar residues expelled from water engender a molecular interior where they can be buried. Paradoxically, results of earlier quantitative analyses have suggested that the tendency for nonpolar residues to be buried within proteins is weak. However, such analyses merely classify residues as either "exposed" or "buried." In the experiment reported in this article proteins of known structure were used to measure the average area that each residue buries upon folding. This characteristic quantity, the average area buried, is correlated with residue hydrophobicity. PMID- 4023715 TI - Morphological novelty in the limb skeleton accompanies miniaturization in salamanders. AB - Salamanders of the genus Thorius (Plethodontidae) are among the smallest tetrapods. Hypotheses of limb skeletal evolution in these vertebrates were evaluated on the basis of estimates of natural variation, comparisons of skeletal homology, and analysis of molecular phylogeny. Nine carpal arrangements occur in Thorius, more than in all twelve related genera of typically larger salamanders; six of these arrangements are unique. They represent a trend toward a decrease in the number of separate cartilages that is independent of locomotor and ecological specialization. Miniaturization may be an important source of morphological novelty, distinct from local adaptation, in vertebrates. PMID- 4023716 TI - Relation of spectral types to oil droplets in cones of turtle retina. AB - The spectral sensitivities and color of oil droplets of cone photoreceptors in the retina of the red-eared turtle (Pseudemys scripta elegans) were investigated by intracellular recording and injections of Lucifer yellow dye. Six morphological types of cones could be distinguished by the color of the oil droplets located in the outermost inner segments. Single cones containing either red or pale green oil droplets were sensitive to red light, cones with yellow oil droplets to green, and cones with clear oil droplets to blue. Contrary to previous reports, both principal and accessory members of double cones were sensitive to red, and no diffusion of dye was detected between the two apposed members. Thus, the oil droplets provide a reliable morphological basis for further investigation of the neuroanatomical networks underlying the processing of color information in the vertebrate retina. PMID- 4023717 TI - NIH to award 2200 new grants. PMID- 4023718 TI - Growth regulation of human melanocytes: mitogenic factors in extracts of melanoma, astrocytoma, and fibroblast cell lines. AB - Melanocytes derived from fetal or adult skin do not propagate in vitro unless cultured in the presence of factors such as 12-O-tetradecanoylphorbol 13-acetate (TPA). In a search for physiological factors regulating the growth of melanocytes, extracts of various cultured cell types were tested. Factors produced by melanoma and astrocytoma cell lines support continued proliferation of melanocytes in the absence of TPA. WI-38, a fibroblast cell line derived from human embryonic lung, was the most active source of melanocyte growth factors. No melanocyte growth-promoting activity was found in extracts of cultured neuroblastoma, renal cancer, normal keratinocytes, or renal epithelium. Nerve growth factor, epidermal growth factor, melanocyte-stimulating hormone, transforming growth factor-beta, and platelet-derived growth factor did not have growth-promoting activity for melanocytes. The presence of melanocyte growth factors and TPA together resulted in the strongest mitogenic activity for melanocytes, permitting the recovery (at 20 days) of 4 to 20 times as many cells as in growth factor or TPA alone. PMID- 4023719 TI - Hallucinogenic amphetamine selectively destroys brain serotonin nerve terminals. AB - (+/-)-3,4-Methylenedioxyamphetamine (MDA), an amphetamine analog with hallucinogenic activity, produced selective long-lasting reductions in the level of serotonin, the number of serotonin uptake sites, and the concentration of 5 hydroxyindoleacetic acid in rat brain. Morphological studies suggested that these neurochemical deficits were due to serotonin nerve terminal degeneration. These results show that MDA has toxic activity for serotonin neurons in rats and raise the question of whether exposure to MDA and related hallucinogenic amphetamines can produce serotonin neurotoxicity in the human brain. PMID- 4023720 TI - Tissue factor gene localized to human chromosome 1 (1pter----1p21). AB - Tissue factor (tissue thromboplastin, coagulation factor III), a protein component of cell membranes, is an essential cofactor for factor VII-dependent initiation of blood coagulation. Since no tissue factor-deficient condition has been described, it is one of only a few proteins of the coagulation system for which the pattern of inheritance has not been ascertained. Because of the species specificity of tissue factor activity and the availability of a very sensitive chromogenic assay, it was possible in the present study to use somatic cell hybrids to assign the chromosomal location of the tissue factor structural gene (F3) to human chromosome 1 (1pter----1p21). PMID- 4023721 TI - Serum iron, total iron-binding capacity, transferrin and haptoglobin concentration in schizophrenic patients. PMID- 4023722 TI - The doctor-patient relationship. PMID- 4023723 TI - Medical students' attitudinal change associated with mental hospital experience. PMID- 4023724 TI - Effect of lipophilicity on the rate of diffusion of sensitizers into cellular targets. PMID- 4023725 TI - Renal papillary necrosis: retrospective post-mortem study. PMID- 4023726 TI - Colorectal cancer in Singapore: preliminary report of the Colorectal Cancer Project from the University Department of Surgery, NUS. PMID- 4023727 TI - Spontaneous pneumothorax occurring in flight. PMID- 4023728 TI - Carcinoma of the stomach. A clinical study. PMID- 4023729 TI - Chondroblastoma: a clinical and radiological study of 104 cases. AB - The clinical and radiographic findings in 104 patients with chondroblastoma are presented. Pain was an almost constant presenting complaint, often accompanied in the case of para-articular lesions by impaired function of an adjacent joint. The majority (80%) were in long bones with a mean age of presentation of 16 years. The characteristic radiological image of these lesions was an eccentric radiolucency, having a sharply defined sclerotic margin and containing areas of calcification in approximately a third of cases. They were always related to a growth plate. Nearly half were confined to the affected epiphysis or apophysis itself, but most of the remainder had traversed the growth plate to involve also the adjacent metaphysis. The bones around the knee and the proximal ends of the humerus and femur were the sites of predilection. A minority (20%) affected flat bones and short tubular bones of the hand and foot, with a peculiar affinity for the calcaneus and talus. The mean age of presentation of these was 28 years. The radiological pattern was similar, except for a greater tendency to expand the affected bone. Complications included the formation of a secondary aneurysmal bone cyst in 16 cases (10 of them in long bones), one malignant chondroblastoma, and one fibrosarcoma developing after radiation of the original chondroblastoma. PMID- 4023730 TI - Bone changes from prostaglandin therapy. AB - Prostaglandin E therapy in infants causes periosteal elevation. Although the changes usually take 30-40 days to become visible, we have seen them as early as nine days. In 15 infants who had prostaglandin E therapy for over six days, three developed periosteal elevation. Three other cases are described in greater detail, with long-term follow-up in two in which the bone remodeled to normal. Gallium scan in one showed increased uptake in areas involved. The periosteal cloaking may mimic Caffey disease but the pattern of involvement is different, since the mandible, which is commonly affected in Caffey disease, is rarely involved in prostaglandin E therapy. PMID- 4023731 TI - Cheirolumbar dysostosis and constitutional narrowness of the cervical spinal canal. AB - In this paper we describe the second case of cheirolumbar dysostosis associated with constitutional narrowness of the cervical spinal canal. This case is the 32nd case of cheirolumbar dysostosis described in the literature. Cheirolumbar dysostosis is not a rare dysostosis and may occur in association with various anomalies. PMID- 4023733 TI - Case report 319. Sickle cell anemia (homozygosity for hemoglobin S) affecting the calvaria. PMID- 4023732 TI - Case report 311. Sternocostoclavicular hyperostosis (SCCH). PMID- 4023734 TI - Case report 320. Localized eosinophilic fibrohistiocytic lesion of bone (tibia)- a localized form of mastocytosis. PMID- 4023735 TI - Case report 321. Extraosseous chondroblastoma in the subcutaneous tissues of the right shoulder. PMID- 4023736 TI - Case report 322. Chordoma of the body of C2 in cases 1 and 2. PMID- 4023737 TI - Sliding-screw plate fixation of proximal femoral fractures: radiographic assessment. AB - The sliding compression screw-sideplate combination is currently the most widely employed device for internal fixation of stable and unstable intertrochanteric fractures of the femur. The normal and abnormal radiographic appearances of this device in the immediate post-operative period are discussed. Potential long-term complications including mal- or non-union, intra-articular penetration, metal failure, rotation of the proximal fracture fragment, disengagement, trochanteric bursitis, leg length discrepancy, delayed cervical stress fracture, and ischemic necrosis are reviewed. PMID- 4023738 TI - "V" shaped predens space. AB - "V" shaped widening of the predens space (PDS) in flexion can be a worrisome finding in trauma patients, possibly representing injury to the transverse ligament. These patients may also show widening of the C-1/C-2 interspinous distance. We think this appearance is usually due to increased flexion mobility at the atlantoaxial level with developmental elongation or laxity of the cranial end of the transverse ligament and/or the posterior ligamentous complex. Tearing of only the cranial end of the transverse ligament must be extremely rare, if it occurs at all; there is no reported proven case. Tearing of only posterior ligaments seems possible and should be evaluated clinically. PMID- 4023739 TI - Nutrient canals of the ilium: a normal variant simulating disease on computed tomography. AB - The nutrient canals of the ilium are a frequent finding on computed tomography (CT), and were seen in 8 of 8 consecutive examinations of the pelvis. CT sections through these canals could be misinterpreted as fractures or metastases, especially if there is a history of pelvic trauma or malignancy elsewhere. PMID- 4023740 TI - Anterior process fractures of the calcaneus. AB - Fractures of the anterior process of the calcaneus are often missed. This error follows from the tendency to focus exclusively on the mortise and malleoli when a history of ankle trauma is supplied. Seven patients with this fracture are presented. The anatomy, mechanism of injury, clinical presentation, and the radiographic features of this injury are discussed. PMID- 4023741 TI - Dermatomyositis with calcinosis cutis. Case report 317. PMID- 4023742 TI - Periosteal hemangioma of left fibula. Case report 324. PMID- 4023743 TI - Benign neurilemmoma in the posterior soft tissues of the right thigh. Case report 325. PMID- 4023744 TI - Lipoma of chest wall. Case report 326. PMID- 4023745 TI - Arteriovenous malformation eroding the right femoral neck. Case report 327. PMID- 4023746 TI - Isolated cryptococcus osteomyelitis of the humerus simulating a neoplasm of bone in a patient with sarcoidosis. Case report 329. PMID- 4023748 TI - Early Legg-Perthes disease (ischemic necrosis of the femoral head) demonstrated by magnetic resonance imaging. AB - A case of early Legg-Perthes disease (ischemic necrosis of the femoral head) is presented to illustrate the value of magnetic resonance imaging (MRI) in demonstrating the presence of and extent of alterations of intensity of the ischemic femoral epiphysis compared with the normal. The unique advantages of flexible imaging planes and ability to perform follow-up examinations without the hazards of ionizing radiation are stressed. PMID- 4023747 TI - Synovial cysts of the hip joint and iliopsoas bursitis: a spectrum of imaging abnormalities. AB - Synovium-related soft tissue disease around the hip constitutes a spectrum ranging from isolated iliopsoas bursitis to pure articular synovial herniations without bursal involvement. The clinical, pathologic, and radiographic features of these entities are discussed as they pertain to the variety of underlying disorders which predispose to their occurrence. Nine case reports are utilized to illustrate the variable clinical and radiographic presentations which may be encountered. Based upon these cases as well as those in the literature, an imaging algorithm has been developed which should eliminate unnecessary studies and allow prompt and accurate diagnosis. PMID- 4023750 TI - Health risks among enlisted males in the U.S. Navy: race and ethnicity as correlates of disease incidence. AB - A cross-sectional study of all Black and Caucasian enlisted males in the U.S. Navy between 1974 and 1979 was conducted to determine if there were any significant racial group differences in disease incidence. First hospitalization rates for sixteen ICDA-8 diagnostic categories and selected diagnoses were examined and compared on the basis of race, age, year hospitalized, education and occupation. Results indicated that total disease incidence among Black males has declined in the past decade, with a reduction in total first hospitalizations from 1652 per 10,000 men in 1974 to 1088 per 10,000 men in 1979. Total incidence rates for Caucasian males in the same period declined from 1347 per 10,000 men to 1100 per 10,000 men. However, Blacks were found to be at significant risk for: mental disorders; diseases of the genitourinary system; diseases of the circulatory system; diseases of the digestive system; diseases of the blood and blood-forming organs; symptoms and ill-defined conditions; supplementary classifications; and diseases of the musculoskeletal system. Caucasians had significant higher incidence rates for diseases of the skin and subcutaneous tissue, and accidents, poisonings and violence. Nevertheless, the study results indicated that the populations of Blacks and Caucasians in the Navy are not uniform with respect to disease incidence. There exist numerous subgroups within either racial group, defined on the basis of certain demographic and social characteristics, which are at risk for particular diseases. In addition, the relationship between race and disease is mediated by several factors, including genetic predisposition, socioeconomic status and cultural patterns of belief and behavior. No single factor can account for the excess risk for all diseases among all members of either racial group. PMID- 4023749 TI - Monarticular involvement of the manubriosternal joint. AB - Four females and two males with seronegative monoarthritis of the manubriosternal joint are reported. Two patients had pustulosis palmoplantaris, one psoriasis vulgaris, and one HLA-B27. The arthritis is considered to be a monoarticular manifestation of seronegative spondylarthritis. Two patients had no other diseases or signs. Four patients were followed for a mean of 8.5 years (range 2 16 years) during which time affection of other joints or the spine was not seen. PMID- 4023752 TI - The frontier of modern Western medicine in Nepal. AB - Using the concepts frontier and interface the introduction and spreading of modern Western medicine in Nepal and its relations to other medical systems are described and analyzed. Medical systems do not prevail in the same degree in all places; we may call the geographic areas of concentration the core areas or center(s) of medical systems and the remaining areas their periphery. The frontier of a medical system is defined as that part of the periphery where the presence of the system is increasing. The place of the frontier, its width and the forms in which a medical system appears at its frontier are determined by both internal dynamics and contextual factors. In non-socialist countries like Nepal the dynamics of modern Western medicine are characterized by three tendencies: centralization, expansiveness and a commercial and capitalist character. Some important contextual factors which have been shaping the frontier in Nepal are: migration, including tourism, labor-migration and trade; the role of foreign aid and geographical conditions. The situation at the frontier has an important influence on the nature of the interface between modern Western medicine and other medical systems. In the article Faith-healing, Ayurvedic medicine, Homeopathy and Tibetan medicine are described briefly and the interface between them and modern Western medicine is looked into. PMID- 4023751 TI - Sources of influence on infant feeding practices in Hong Kong. AB - The breastfeeding rate in Hong Kong is low compared to the rates in Western countries. To understand the relative importance of different sources of influence on infant feeding practices, 714 Chinese mothers with infants aged 4 weeks to 6 months were studied. It was found that the bottlefeeding mothers were influenced more by the medical professionals who did not support breastfeeding. This influence was further reinforced by the mass media and particularly television advertisements on infant formulae. The successful breastfeeding mothers, on the other hand, were influenced more by their social networks through which they were told of the dangers of bottlefeeding. The failed breastfeeding mothers differed from the other groups in the lack of support they experienced from friends and relatives. Although they received professional encouragement to breastfeed, they were more sheltered from the influence of mass media and social networks. From these findings, it is suggested that different sources of influence are related to different feeding practices. However, to be able to continue with the practice that one has chosen, the availability of social support is essential. Implications of these findings are discussed and several recommendations to promote breastfeeding are made. PMID- 4023753 TI - Self-touching as an indicator of underlying affect and language processes. AB - In this study of 28 physicians and their patients during the medical interview, information is presented on a class of nonverbal behavior, self-touching, thought to represent states of negative affect. A more recent perspective suggests that self-touching is associated with cognitive processing. The results of the present study focused on differences in types of self-touching by patients and physicians, semantic content of utterances when self-touching was displayed, and temporal location of self-touching within the speech stream. These are considered with respect to affective and psycholinguistic theories of self-touching. The results lend support to the notion that self-touching is exhibited in relation to information processing and production, in addition to negative affect. PMID- 4023754 TI - Professional identification: a study of female students at a medical college in India. AB - This paper explores female medical students' identification with their profession at a medical college in India by comparing it with that of male students. The professional identification is conceptualized as having three elements: career commitment, career-satisfaction and professional self-image, each elicited by a single question. Compared to males, females were found to perceive medicine as more satisfying, and yet they were less sure than males of pursuing a medical career throughout their lives. The female students' commitment to their career was basically conditional, whereas for the males, it was primarily categorical. Additionally, females expressed less professional ambition than males and preferred different specialties. The main thrust of this paper is that the professional identification of both males and females is qualitatively different. The reasons for these differences are sought in sex-role socialization, cultural norms and informal social pressures at home and at the college. PMID- 4023755 TI - The theory of the hospital: a review of the models. AB - This paper presents a survey of the literature on the theory of the hospital. The paper shows that certain methodological difficulties associated with the theory of the firm generally have been transmitted to the analysis of the hospital. It is also argued that structural considerations are of vital importance to the development of the theory of the hospital. Unfortunately such considerations have, with a few exceptions, been ignored in the small number of formal models of the hospital that have been developed. Attention is drawn to the fact that concern should be not only with the market structure within which the hospital operates, but also with the internal structure of the hospital. The survey is developed through the employment of the structure-conduct-performance paradigm, utilized by industrial economics, as a general framework. PMID- 4023756 TI - Effects of promotion on pharmaceutical demand. AB - The research question addressed in this study was, "Do changes in promotional expenditure cause changes in the size of the market (primary demand) or market share (selective demand)?" Two types of promotion were evaluated; sales calls to physicians and medical journal advertising. The sales elasticities of each of these promotional techniques were estimated through the use of ARIMA modeling. The market expansive effects and the market share effects were measured for each of 7 drugs in two therapeutic categories, the benzodiazepines and diuretics. The results of the analysis showed that there was no correlation between changes in detailing or journal advertising expenditures and primary or selective demand. Thus, it was assumed that the primary and selective demand elasticities for pharmaceutical advertising may be equal to zero. Drug manufacturers should evaluate the effects of reductions in their promotional expenditures, changes in promotional content, as well as seek alternative methods of advertising which may have a higher sales elasticity and effectiveness. PMID- 4023757 TI - Sex differences in the psychological reactions of medical and surgical patients to crisis intervention counseling: sauce for the goose may not be sauce for the gander. AB - The psychological reactions of 259 female and 130 male medical and surgical patients were examined. Both when they were discharged and when they were followed up 12 months later, women who received crisis intervention counseling during their hospitalisation showed the predicted psychological gains when compared with non-counseled women. They expressed fewer feelings of helplessness and more of competence in the short term and fewer feelings of anxiety and helplessness in the long term. Men showed some improvements in the short term but fewer in the long term when, although they later expressed more feelings of competence, there were also more of helplessness. Women and men also showed the predicted benefits of counseling similarly in fewer indirect expressions of anger on both occasions. They also showed less anxiety on discharge and fewer depressive feelings on follow-up. Explanations of the sex differences in terms of sex role stereotypes, the extent of each patient's crisis and possible methodological artefacts were considered. PMID- 4023758 TI - Problems of substance abuse: exploitation and control. AB - The notion of substance abuse is highly problematic. There is considerable disagreement amongst 'experts' as to the relative hazards and addictive properties of both legally and illegally available substances. There are also widely divergent sub-cultural attitudes to the harmfulness or benefit of drug use. One can assume no social consensus as to the nature of the contemporary 'drug problem', nor about the most appropriate means of dealing with it. There is, however, considerable evidence that criminalization of drug use, and harsh penalties against users and suppliers, are ineffective and counter-productive. Other models of control need to be considered, and in particular the merits and de-merits of the medicalization of drug abuse require examination. However, this is only one aspect of the problem. On the other side are the national and international corporations and syndicates, both legitimate and criminal, that earn vast profits from trade in toxic substances. Tobacco is legally available in every country in the world, and the industry is rarely subject to strict control. Thus the issue of substance abuse and control should be seen in a global context, in which account is taken of both legitimate and underworld operations. In attempts to control international trade in toxic substances, the limited success and the problems of already existing legal controls should be acknowledged. Local awareness and regulation of trade in substances is essential, but not sufficient. Amongst other avenues to be explored is the possibility of diverting presently illicitly grown narcotics into indigenous pharmaceutical industries in the Third World. Some problems with this strategy are noted.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4023759 TI - Discrimination against women in the South African medical profession. AB - The paper examines discrimination against women in the medical profession in the South African context. To measure the extent of the problem data was obtained from the records of one of the largest South African medical schools--the University of the Witwatersrand Medical School. This medical school is one of the most liberal in South Africa and does not discriminate against women in its admission policies and the number of women graduated as doctors has increased steadily. Despite this, women take a secondary place in the South African medical profession. Evidence for this was collected from official records and supplemented with guided interviews with 15 women doctors. Special attention is given to the serious under-representation of Black women doctors in South Africa. PMID- 4023760 TI - A need for community education in development: the Mit Abu El Kom case. AB - A quasi-experimental study was performed in Mit Abu El Kom Village, Egypt, where one-quarter of the 500 village households had been provided with new housing and indoor water and sanitation facilities and where, prior to this provision, water and sanitation facilities were inadequate or nonexistent among all households. No community health education had taken place among relocatees (subjects) or nonrelocatees (controls) in conjunction with the provision of water and sanitation facilities. This study investigated if subjects' access and exposure to facilities had alone been sufficient to significantly alter their relevant knowledge, attitudes and practices as compared to controls. This was accomplished primarily through structured household interview. Given that women are traditionally most affected by facilities and most effective in matters related to household health, one adult female from each sampled household was the respondent, totalling 123 for subjects and 111 for controls. Between-group comparisons of responses revealed overall nonsignificant differences in knowledge and attitudes and that respondent age and sex had no significant overall impact on responses. Age and sex were also discounted as affecting variables in within group response analyses. Some significant changes in practices had occurred among subjects. However, these mainly resulted out of convenience and their potential benefits were often denigrated by changes which had not occurred or had not continued. The data indicate a need for community health education if health related benefits of water and sanitation facilities are to be realized, and specifically indicate the need to address the educational needs of all village women. PMID- 4023761 TI - The social definition of women's smoking behaviour. AB - The history of women's smoking behaviour is one of changing normative definitions. Recent trends have been explained in terms of the symbolic value of smoking, representing for women freedom and independence. This view is emphasised by advertising. However, other evidence suggests the continued existence of an older, more negative cultural stereotype. A two-part study of young women undergoing professional training for nursing and teaching throws some light on the way in which female smoking behaviour is currently socially interpreted. The first phase indicated that among the minority of parents who had expressed their attitudes towards their daughter's smoking in relation to sex-role norms, smoking was presented as unacceptable for women. More than half the sample perceived a negative cultural stereotype to be operating in contemporary society and two thirds recognised its existence in the past. This stereotype presents smoking as a male behaviour and hence inappropriate for women. Women who do smoke are liable to be labelled as having unfeminine or degrading attributes. The stereotype operated more strongly in the general social background rather than in reference to personal relationships and hence its influence on contemporary behaviour is likely to be limited. It was rejected as out-dated or a male belief by some but nevertheless it represented the personal opinion of others. In terms of a more favourable definition the female smoker was perceived in terms of an elegant/sophisticated dimension and in relation to an extrovert personality. The view of sample members that the growing acceptability of women's smoking was related to social change indirectly supported the view that sees smoking as symbolic of independence. Those who saw smoking in neutral terms, i.e. as not having sex-role attributes, perceived smoking in this sense as normal social behaviour for men and women alike. The second phase suggested that smokers and non-smokers have divergent views about the image of the female smoker. The non smoker's image was based on the older cultural stereotype ('unladylike'), whereas the smokers were more likely to take a view corresponding to the perspective that sees women's smoking as symbolic of social change and greater independence ('liberated'). The non-smokers had a clear and positive image of 'girls who don't smoke' ('feminine'), whereas for smokers the female non-smoker lacked a distinctive identity. The study thus suggests that traditional concepts of appropriate female behaviour continue to inhibit smoking among some women, whereas others perceive it as an aspect of independent behaviour.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 4023762 TI - Smoking and intelligence in Australia. AB - It is difficult to test the link between intelligence and smoking directly. A hypothetico-deductive approach is therefore used and it is hypothesized that members of the Mensa club will have low rates of smoking. A postal survey of 402 Australian Mensa members revealed incidence rates of 22% for males and 15% for females. This is roughly half the general population incidence rate in both Australia and the U.K. It is concluded that the results do support the view of smoking as a sign of general social disadvantage. PMID- 4023763 TI - Relativism in the diagnosis of hypoglycemia. AB - It is a common assumption in our medicalized society that diagnostic labels simply describe facts, rather than express the diagnostician's own concepts of anomaly and dysfunction. Variability among physicians in diagnosing reactive hypoglycemia illustrates some fundamental problems of reifying the concept of disease. Although most physicians consider the same three variables in this diagnosis, their interpretations of them may vary widely. The disagreement centers around the credibility given standardized, technological measures versus the individual patient's experiences. Most physicians consider lab tests definitive in diagnosing hypoglycemia, while bypassing patients' subjective reports. Some, however, rely more heavily on patient-generated criteria to diagnose the condition. This lack of agreement about the criteria for diagnosing hypoglycemia, coupled with the psychological nature of many of the symptoms, make hypoglycemia and psychological disorder reasonable alternative diagnoses. These diagnoses, in turn, have very different effects on patients. These variations in physicians' diagnostic criteria illustrate that diagnostic labels are cognitive constructs, subject to the influence of the physician's culture, expectations, values and interests. PMID- 4023764 TI - Nutrition, lactation and fertility in two Mexican rural communities. AB - Policies are currently being pursued in Third World countries which promote lactation as both a fertility control measure and a means of improving child health and decreasing infant mortality rates. However, the relationship between nutrition, lactation and fertility in the human is a complex one in which social and psychological factors are involved as well as physiological and biochemical mechanisms. Little is known about the effects of these social and psychological variables on the biological processes. Observations made in the course of the anthropological fieldwork study reported in this paper raise questions regarding the assumption of the universal applicability of lactation policies in third world countries. Findings from this study are supported by the anthropological literature which indicates that breast feeding behaviour is culturally patterned and that there is a wide variation in such behaviour. The variations in environmental resources as well as in the ideological notions of nutrition which pattern the behaviour governing the exploitation of such resources as well as feeding behaviour is seen as advantageous in that they provide a 'natural laboratory' situation for examining the conflicting hypotheses concerning the relationship between nutrition, lactation and fertility. PMID- 4023765 TI - Patient mobility for elective surgical interventions. AB - In this study, we address the question of patient mobility by defining three types of mobility and testing them with a Probit model. First, we have forced mobility (shortage of resources), second, physician-induced mobility (hospital affiliations) and finally, the mobility chosen by patients. We isolate explanatory variables for observed patient mobility for the year 1977-1978 in Quebec, Canada, and present the results for two specific surgical interventions. We found that forced and induced mobility are statistically significant in explaining the movements of patients in search of specific medical services. However, the mobility chosen by patients requires further investigation. PMID- 4023766 TI - [Changes in the UV spectrum of the vitreous body in relation to the time of death]. AB - The UV spectrum of 40 samples of vitreous body was determined in different time periods after death. The vitreous body was diluted in the ratio 1:200 and 1:400 by means of redistilled water. It was found that the ratio of absorbance corresponding to the peaks of the curve is dependent on the time period after death. The regression analysis determined an exponential relation, making possible to estimate the time period after death in the dilution of the vitreous body in the ratio 1:200. For this kind of determination cases of deceased persons with damaged brain or cases with too high an absorbance did not prove suitable. In the dilution 1:400 the variance was too high and did not provide data that would be suitable for determining an estimate of the time elapsed from death. PMID- 4023767 TI - [Determination of alcohol in the blood using the "head space" automatic analyser, Erba Science and the Czechoslovak-made Chrom 4 chromatograph]. AB - The connection of Carlo Erba automatic sampler with gas chromatograph Chrom IV is described. There are presented the results of the analyses of alcohol in blood. The results were obtained with the aid of this two instruments. PMID- 4023768 TI - [Possibilities and pitfalls in the determination of group characteristics in the remains of historical persons]. AB - The authors give an account of their experience with the assessment of group substances from skeletal remnants of historical persons and Egyptian mummies. They also draw attention to possible pitfalls of examinations and the interpretation of results. PMID- 4023769 TI - False diagnosis of persistent fetal circulation caused by misplacement of umbilical artery catheter. AB - We have described two cases in which persistent fetal circulation was mistakenly diagnosed because umbilical artery catheters were placed in too high a position. In one case, repeated doses of tolazoline were given unnecessarily. While high placement of umbilical artery catheters is commonly accepted, misplacement may not always be apparent on routine AP chest films taken to confirm catheter positioning. PMID- 4023770 TI - Macrocystic peritoneal mesothelioma. PMID- 4023771 TI - Home ventilator dependence after high cervical cord injury. AB - Home ventilator support, though somewhat unorthodox, is economically desirable and is now technically feasible. Close cooperation between public health providers, ventilator suppliers, and the family physician, as well as strong patient and family compliance, is essential for success in maintaining a ventilator-dependent patient at home. PMID- 4023772 TI - Child abuse manifested as factitious apnea. AB - A 6-week-old male infant was admitted for near-miss SIDS documented in the hospital. The episodes were subsequently found to be factitious apnea that occurred as a result of the father suffocating the child. Apnea monitoring did not prevent, and in fact perpetrated the illusion of SIDS in this infant. PMID- 4023773 TI - Intrauterine and ectopic pregnancies after a tubal ligation with documented tubal occlusion. AB - The patient described had both an intrauterine and an extrauterine pregnancy after a previous vaginal tubal ligation using a Pomeroy technique. A hysterosalpingogram showed midtubal occlusion. Although pregnancy after tubal ligation is not unusual, this case does show that a hysterosalpingogram may also be inconclusive in ruling out the possibility of future pregnancy. PMID- 4023774 TI - Suspected interaction: warfarin and erythromycin. AB - The patient described had a markedly enhanced response to warfarin when he was given erythromycin concomitantly. Before the initiation of erythromycin, his warfarin anticoagulation had been well controlled. After withdrawal of erythromycin, his response to warfarin returned to normal. These findings and previously reported clinical and laboratory data lead to the conclusion that, at least in some patients, a potentially serious interaction between erythromycin and warfarin can occur. PMID- 4023775 TI - Infectious endocarditis caused by Cardiobacterium hominis. AB - We have described a patient with Cardiobacterium hominis endocarditis who had a paucity of symptoms and ultimately required valve replacement. PMID- 4023777 TI - Surgical specialty training. PMID- 4023776 TI - Branhamella catarrhalis endocarditis in a patient receiving hemodialysis. AB - While Branhamella catarrhalis is now recognized as an important pathogen, this is only the fifth reported case of endocarditis caused by it. The production of beta lactamase by many strains and its resistance to vancomycin and clindamycin complicate the choice of antibiotic therapy. PMID- 4023778 TI - The internship year. PMID- 4023779 TI - Life-style factors among patients with melanoma. AB - For the period 1975 to 1980, melanoma incidence in persons 10 through 49 years of age in a southwest Georgia town was significantly increased compared with US rates (expected = 9; observed = 41) and Atlanta rates (expected = 13; observed = 41). We surveyed 36 white patients with melanoma and 74 unaffected control subjects to identify risk factors possibly associated with melanoma in this population. When compared with the controls, the patients more often had a history of melanoma in family members [odds ratio (OR) = 8.00; 95% confidence limits (CL) = 0.89 to 71.6; P = .063]; skin sensitivity to sun exposure (OR = 1.63; CL = 1.04 to 2.56; P = 0.016); or preexisting pigmented nevi (OR = infinity; one-sided 95% lower limit = 1.94, P = .005). More male patients had melanomas on covered body sites, though 67% of melanomas in both sexes occurred on normally covered sites. Patients in our study also had been exposed more often than controls to sick animals in the year before onset (OR = 3.18; CL = 0.92 to 11.0; P = .055) and to pesticides in nonoccupational settings (OR = 3.56; CL = 0.87 to 14.5; P = .059). PMID- 4023780 TI - Primary gastrointestinal lymphoma. AB - We studied 56 patients with primary gastrointestinal lymphoma to determine the manifestations, diagnostic and treatment methods, and patient outcomes. We identified 27 cases of primary gastric lymphoma and 29 cases of lymphoma involving the remainder of the gastrointestinal tract. Initial symptoms were nonspecific and included abdominal pain, weight loss, nausea, and vomiting. Diagnosis was frequently made at operation, with less than half of the patients having endoscopy and biopsy. The predominant histologic type was diffuse histiocytic lymphoma; the second most common type was poorly differentiated lymphocytic lymphoma. Average survival for patients with gastric lymphomas was 38 months, versus 21 months for those with intestinal lymphomas. The most important prognostic factor was the stage of disease at presentation; spread beyond the regional lymph nodes was associated with shortened survival. Comparison of treatment groups was compromised by the varied combinations of therapy used and by the stages and sites of disease. This study points out the need for prospective randomized clinical trials, with comprehensive staging and uniform therapeutic procedures, to identify the best available methods. PMID- 4023781 TI - Delusions of parasitosis: differential diagnosis and treatment. AB - Delusions of parasitosis, or a patient's persistent belief that he has cutaneous invasion by parasites despite medical evidence to the contrary, is an uncommon syndrome associated with a wide variety of medical and psychiatric disorders. Its prognosis has been improved considerably by the introduction of pimozide, a potent neuroleptic agent. PMID- 4023782 TI - Briquet's syndrome in adolescence. AB - Briquet's syndrome, originally described more than 100 years ago, has recently become a subject of concern for physicians who work with adolescents. It is a chronic disorder that primarily affects women, is characterized by many symptoms involving a number of organ systems, and usually has a frustrating clinical course. It typically begins in the second or third decades, and only rarely subsides with time. Multiple diagnostic procedures, medications, and surgical operations are common, usually without evidence of significant disease. Complications can include substance abuse, depression, and suicide. Management centers upon viewing the symptoms as the patient's attempts to communicate difficulties in coping with stress. PMID- 4023783 TI - Preoperative skeletal traction in Legg-Perthes disease. AB - In four of 11 patients with Legg-Perthes disease for which a varus femoral osteotomy was planned, routine split Russell traction failed to produce complete preoperative containment. Preoperative skeletal traction was used to distract the joint, displace the extruded lateral physis below the acetabular margin, and then reintroduce the femoral head into the acetabulum with progressive abduction. The femoral heads were rated postoperatively as good (two cases), fair (two cases), and poor (one case). Preoperative skeletal traction is an adjunctive treatment method for patients with "hinge abduction" in whom a varus femoral osteotomy is indicated. PMID- 4023784 TI - Long bone defects treated with demineralized bone. AB - This study was undertaken to determine the potential of demineralized bone alloimplant (DBA) for healing long bone defects. We removed 25 mm of bone from the junction of the proximal and middle thirds of both ulnas in seven adult male mongrel dogs. On one side of each animal the devascularized bone was replaced as a cortical autograft (CA) and on the other side, the defect was filled with DBA. Because of implant error, there were only five CAs to evaluate, of which two had achieved clinical union. Of the seven DBAs only one achieved union. The bone in and around the defect was quantified on each specimen roentgenogram and was compared to the size of the original defect. The CA defects were filled 139% +/- 11% with bone that was partly new and partly remnants of the replaced autograft. The demineralized alloimplant defects were filled 143% +/- 45% with bone which, of course, was all newly formed. The difference between the two groups was not significant. We concluded that the DBA was an excellent osteogenic stimulant, but that it did not prevent nonunion in this model. PMID- 4023785 TI - Learning arthroscopy. AB - Problems have been uncovered in learning arthroscopy at the resident level or for the beginner at any level of orthopedic practice. The problems are varied, and are not all present in the same individual. This study delineates problems involving vision impairments, depth perception, spatial recognition, speed of accommodation, and data confrontation requiring immediate action. Speed is an additional factor in relation to accomplishing a task within an acceptable time limit. Through testing mechanisms, surgeons can discover their own inadequacies and thus learn to perform well in this new field. PMID- 4023786 TI - Fetal chromosome analysis in Virginia: results and complications of 2,288 cases. AB - In reviewing the results and complications of 2,288 consecutive fetal chromosome analyses at the Medical College of Virginia, we found that 48 abnormal fetuses (2.1%) were detected, with age-specific and indication-specific incidences of particular abnormalities (such as Down's syndrome and structural rearrangement) similar to those found in other large series. An unusual finding was a 5.5% incidence of aneuploidy among 55 patients who had antenatal testing because of a history of neural tube defects. The spontaneous abortion rate after amniocentesis was 2.5% from 1976 to 1981, but only 0.9% in 1982 to 1983. Adequate karyotypes were obtained in 99.6% of patients; there were no laboratory misdiagnoses. We discuss the present impact of fetal karyotyping in Virginia, as well as the implications for pregnancy surveillance in the future of the decreasing morbidity of midtrimester amniocentesis and technologic improvements in obstetrics, such as ultrasonography and chorionic villus biopsy. PMID- 4023787 TI - Educational and exercise programs for asthmatic children. AB - We designed programs to teach appropriate exercises to asthmatic children and to educate their parents about their special needs. Each of 11 programs over a six year period included a weekly two-hour session for four weeks. Lectures for parents dealt with the etiology and precipitating events of asthma, environmental control and drug therapy, family interaction with a psychiatrist, and hyposensitization therapy and food allergy. The 59 children, aged 4 to 13, played group games, learned breathing exercises, and were assisted by their parents in postural drainage. School absences decreased in 59%, emergency room visits decreased in 70%, medication usage decreased in 54%, and the number of attacks decreased in 70%. Greater understanding of asthma by both parents and children improved the quality of life and lessened the severity of the disease. PMID- 4023788 TI - Palatal insufficiency: a surgical technique for reconstruction. AB - Nasal regurgitation and hypernasality are the major complications after extirpation of the soft palate, retromolar trigone, and tonsillar areas. The surgical procedure described herein provides satisfactory correction of the defect. The combined approach of advancement-rotation palatoplasty and an advanced lateral pharyngeal wall flap appears to be an alternative solution to the use of an obturator or inferiorly based pharyngeal flap. PMID- 4023789 TI - Empty right iliac fossa. AB - In the diagnosis of intra-abdominal disease, absence of gas or fecal shadows from the right iliac fossa is an important but nonspecific finding on plain roentgenograms. We found the empty right iliac fossa most commonly associated with acute appendicitis, Crohn's disease, and carcinoma of the cecum. Retrospective analysis of 137 confirmed cases of disease in the right lower quadrant yielded 21 (15.4%) with an empty right iliac fossa. In an additional 21 cases, an empty right iliac fossa was prospectively identified, and 13 of these patients (61.9%) had confirmed disease in a particular area. PMID- 4023790 TI - Cephalosporins for surgical prophylaxis: computer projections of intraoperative availability. AB - Cephalosporin antibiotics are the most frequently used agents for surgical prophylaxis. Within this class are considerable pharmacokinetic variations that could have significant implications. We used a computer simulation of cephalosporin serum levels to describe concentrations achieved and maintained intraoperatively when the agents are given intravenously "on call" to the operating room or with induction of anesthesia. Intraoperative serum concentrations fall below 1 microgram/ml if an operation lasts longer than 2.3, 2.7, 3.8, or 4.0 hours when cephalothin, cephapirin, cefamandole, or cefoxitin, respectively, is given in usual doses upon induction of anesthesia. When the same agents are given intravenously on call to the operating room, intraoperative serum concentrations fall below 1 microgram/ml for operations lasting longer than 1.1, 1.5, 2.6, or 2.8 hours, respectively. If cephalothin, cephapirin, cefamandole, or cefoxitin is used, it should be given at induction of anesthesia to provide maximal intraoperative serum concentrations. The longer half-life of cefazolin, ceforanide, cefonicid, and cefuroxime is a potential advantage because serum concentrations of these agents are well above 1 microgram/ml for as long as eight to 22 hours even after on-call administration. PMID- 4023791 TI - Microsurgical vasovasostomy for reversal of elective bilateral segmental vasectomy. AB - Microsurgical vasovasostomy for the reversal of elective bilateral segmental vasectomy (vasectomy, vas ligation) was done in 57 patients (61 operations) between May 1977 and March 1984. The length of time between elective segmental vasectomy and subsequent vasovasostomy ranged from 12 to 216 months; the longest period between vasectomy and vasovasostomy resulting in a subsequent pregnancy was 108 months. The patency rate was 83%, with 51% of these patients fathering one or more children (overall pregnancy rate of 41%). Unlike previous studies, ours showed no positive correlation between the presence of postvasectomy sperm granulomas and either patency or pregnancy rate after microsurgical vasovasostomy. The major factor that seemed to affect the success of the procedure was the number of years between vas ligation and vasovasostomy. PMID- 4023792 TI - Inability of awake patients to correctly locate a cough stimulus. AB - To determine whether patients can accurately identify the lung in which a cough reflex originates, a unilateral cough stimulus was administered to 67 patients during fiberoptic bronchoscopy. Although the stimulus produced a vigorous cough reflex in all subjects, 51 of 67 individuals were unable to identify the side stimulated. These results suggest that impulses from endobronchial irritant receptors are not perceived cortically as originating within a particular hemithorax. PMID- 4023793 TI - Response to aminoglutethimide after failure of tamoxifen therapy in breast cancer. AB - A 54-year-old woman had a primary breast cancer with an estrogen receptor of 11.9 fmoles/mg of protein. One year later bony metastases were treated with tamoxifen. The disease progressed rapidly, and therapy was changed to aminoglutethimide, which has resulted in an almost complete remission. This case shows that patients who fail to respond to tamoxifen therapy may have a good response to other endocrine manipulation--in this instance, aminoglutethimide. PMID- 4023794 TI - Unilateral adrenal hemorrhage: an unusual presentation. AB - An asymptomatic adrenal mass was discovered in an elderly patient during evaluation of an abnormal urinary sediment. Exploratory laparotomy revealed an adrenal hematoma as the cause of the mass. No clear cause of the adrenal hemorrhage was identified, and postoperatively there was no evidence of adrenal insufficiency. Though rare, signs of adrenal hemorrhage may include an asymptomatic adrenal mass, and should be considered in the differential diagnosis of this problem. PMID- 4023795 TI - Left atrial myxoma and atrial septal defect with recurrent pulmonary emboli. AB - We have reported a case of left atrial myxoma in association with an atrial septal defect in a patient followed up over a number of years for recurrent sterile pleural effusions and chronic obstructive lung disease of undetermined cause. During hospitalization for pneumonia, an intracardiac mass and atrial septal defect were found by echocardiography, and verified at operation to be a left atrial myxoma. PMID- 4023797 TI - Therapeutic indications in carbamazepine overdose. AB - After ingesting carbamazepine, our four patients had elevated serum drug levels but minimal symptoms and were treated conservatively with excellent results. While serum levels may provide the diagnosis, they do not indicate therapy, which depends upon clinical manifestations. PMID- 4023796 TI - Dopamine- and norepinephrine-secreting intrapericardial pheochromocytoma in a normotensive patient. AB - We have described a 41-year-old woman without hypertension in whom laboratory testing showed elevated urinary and plasma norepinephrine levels as well as increased plasma dopamine and enkephalin-like immunoreactivity. A pheochromocytoma was removed from the interatrial wall, but the course was complicated by intractable bleeding and the patient died. The atypical normotensive pheochromocytoma should be suspected in patients with insidious adrenergic symptoms when more routine diagnoses cannot be made. PMID- 4023798 TI - Biology of Robertsiella kaporensis snails and Malaysian Schistosoma. AB - Studies on the bionomics and host-parasite relationship of Robertsiella kaporensis and Malaysian Schistosoma were investigated. The study was divided into 4 parts: cultivation of snails, R. kaporensis, and maintenance of Malaysian Schistosoma life cycle, daily cercarial shedding cycle in R. kaporensis, miracidial load and cercarial shedding pattern and the infectivity of Malaysian Schistosoma cercariae. R. kaporensis were cultured in the laboratory with the use of plastic container provided with fine sand. The snails were fed with diatoms and Saraca leaves. The development period for the snail eggs was about 20-30 days, the young grew to maturity in 14-15 weeks, and the average growth rate of snails was 0.23 mm per week. The daily cercarial shedding cycle of snails had shown that the peak emergence of cercariae of Malaysian Schistosoma occurred at night, between 6-10 pm. The miracidial load which yielded the best results in terms of percentage infection rates of snails and cercarial output was the miracidial concentration of 8 miracidia per snail. The study on infectivity of Malaysian Schistosoma cercariae has shown that there was a decrease in infectivity of the cercariae to mammalian hosts as the cercariae increased in age. The percentage infection rate of mice and numbers of worms recovered were highest in mice infected with cercariae of 0-1/2 hr. old. Infection of cercariae fell rapidly after the cercariae were 16 hr. old. PMID- 4023799 TI - Kawasaki disease in Songkla, Thailand. AB - Four cases of Kawasaki disease hospitalized in Haadyai Hospital, Songkla, during 1978-1983 are summarized. All four patients had clinical features, the principal signs and symptoms set forth in the guidelines for the diagnosis of mucocutaneous lymphnode syndrome (Kawasaki disease) including other associated features such as diarrhea, arthritis, mild jaundice, pneumonia, subconjunctival hemorrhage, proteinuria and leukocytosis. All four patients survived the acute illness, without evidence of cardiac complications. The cases were followed-up for over one year. PMID- 4023800 TI - ELISA testing in cases of clinical angiostrongyliasis in Thailand. AB - The sera from 116 Thais admitted to Nakhon Ratchasima hospital in northeastern Thailand with eosinophilic meningitis were tested for antibodies to Angiostrongylus cantonensis by ELISA. Ninety-six percent of the sera were considered positive with ELISA values exceptionally high for most patients. The clinical aspects of the disease are also presented. The ELISA test is considered to be of value in the diagnosis of the disease but tests for the antigen would provide a more definitive diagnosis. PMID- 4023801 TI - NAG Vibrio cholerae isolated from imported shellfish in Guam. AB - A survey of imported shellfish available in public markets on the Island of Guam revealed the presence of NAG Vibrio cholerae contamination (10 of 38 sample lots positive) and high coliform counts (21 of 33 sample lots in excess of 2400 per 100 grams). NAG V. cholerae contamination was associated with high coliform counts and origin in fresh or brackish waters rather than saltwater. Further importation of fresh shellfish from other than approved sources was prohibited. PMID- 4023802 TI - Effect of passive immunity to tetanus in DTP vaccinated infants. AB - Tetanus antitoxin levels in DTP unvaccinated and vaccinated infants whose mothers had either received no dose or two doses of absorbed tetanus toxoid at present pregnancy were determined by the enzyme immunosorbent assay (EIA). It was found that the percentage of protective infants born from non-immunized and immunized mothers were 95.4 and 100 respectively. The transplacental tetanus immunity in infants of immunized mothers was higher than those of non-immunized mothers, however, it was significantly reduced in both groups of infants within two months. After the first dose of DTP vaccine, infants born from non-immunized mothers were able to respond well in producing antibody whereas the infants from immunized mothers were not. In the second and third dose of DTP vaccine both groups of infants had a similar range of tetanus antitoxin. PMID- 4023803 TI - Short term maintenance of Gnathostoma larvae in vitro without losing infectivity. PMID- 4023804 TI - Trombiculid mites of Sunter, North Jakarta Indonesia. PMID- 4023805 TI - Status of Anopheles malaria vectors in Indonesia. AB - During eight years (1975-1984), approximately 46 species of Anopheles have so far been detected by entomological team of Directorate General Communicable Disease Control in Indonesia. Eighteen species of Anopheles have been confirmed as malaria vectors and seven species which consist of: An. sundaicus, An. subpictus An. aconitus, An. balabacensis, An. barbirostris, An. punctulatus and An. minimus have been reconfirmed as malaria vectors, during 1975-1984. An. sundaicus and An. aconitus are the main vectors in Java (reconfirmed 1979-1980-1982). An. sundaicus is predominantly exophilic and exophagic. It is mostly anthropophilic except in Central Java and Yogyakarta where the Human Blood Index (HBI) of An. sundaicus is too low (1.31%). Based on susceptibility tests done during period 1980 to 1983, no An. sundaicus resistance to DDT has been recorded in Java. An. aconitus is the main vector in island of Java. Although mostly exophilic, exophagic and zoophilic, in some places (Central Java) it may still be a dangerous vector. An. aconitus resistance to DDT have been recorded in Central Java, Yogyakarta and large part of East Java. Based on few tests done in Java, An. aconitus is still susceptible to dieldrin and organophosphates i.e. malathion and fenitrotion. Malaria vectors in Outer Islands (outside Java), are predominantly exophilic and exophagic and are still susceptible to DDT. There might be some complexes confronting malaria control programme, which could be An. aconitus, An. Sundaicus and An. balabacensis in Indonesia. PMID- 4023806 TI - Status of malaria vectors in Malaysia. PMID- 4023807 TI - Vectors of malaria in the Philippines. PMID- 4023808 TI - Impact of ecological changes on Anopheles vectors of malaria in some countries of Southeast Asia. PMID- 4023809 TI - Environmental management in mosquito control. PMID- 4023810 TI - Brugia malayi: serum dependent cell-mediated reactions to microfilariae. AB - Sheathed and exsheathed microfilariae of Brugia malayi are killed by normal rat cells in the presence of immune serum in vitro. Immune serum heated at 56 degrees C for 1 hour lost this activity which was largely restored by the addition of fresh normal rat serum. EDTA but not EGTA abolished this activity indicating the operation of complement by alternate pathway. Fresh normal rat serum alone promoted cellular adherence without exerting cytotoxicity to the microfilariae. The activity in the immune serum could be removed with Staphylococcus aureus cells containing Protein A or anti-IgG antiserum. The activity could also be absorbed to and eluted from Protein A--sepharose CL-4B suggesting the involvement of IgG. Neutrophils and macrophages participate in the antibody dependent cell mediated cytotoxicity phenomenon. Eosinophils while adhering to the microfilariae exert cytotoxicity only to the exsheathed parasites. PMID- 4023811 TI - Chemical control on malaria vector Anopheles aconitus in Central Java, Indonesia. PMID- 4023813 TI - Malaria control strategies: overview of changing perspectives. PMID- 4023812 TI - Biological control of mosquitoes, especially malaria vectors, Anopheles species. PMID- 4023814 TI - Induction of protective immunity against infection by Angiostrongylus cantonensis in rats. AB - Attempts were made to induce acquired immunity against Angiostrongylus cantonensis infection by immunizing rats with somatic (L3S) and metabolic (L3ES) antigens from third-stage larvae and with somatic antigen from adult female worms (FACE) via either a combined intraperitoneal and oral (IP-OR-OR) or subcutaneous (SC-SC-SC) route. The most effective mean in inducing protection was the administration of L3S by the IP-OR-OR route, as judged from reduced mortality, prolonged survival periods and/or reduced worm burdens. Such a protocol reduced mortality to below 20% of the unimmunized controls. The worm burden of the L3S immunized rats was only about 25% of the control value and the survival period was at least double. However, judging from gross morphology, the absence of stunted growth and unimpaired ficundity of the worms that developed into adult stage, it appears that those worms that survived had normal development. The latter observation is in contrast to that noted with FACE immunization which seemed to affect also the growth and development of worms that survived into adult stage. PMID- 4023815 TI - Effects of a juvenile hormone analogue on the morphology and biology of Aedes scutellaris malayensis Colless (Diptera: Culicidae). AB - Effects of 2-methyl-9(4-isopropylphenyl)-2,6-dimethyl nonane, or MV-678, a juvenile hormone analogue, on Aedes scutellaris malayensis Colless were investigated under laboratory conditions (29 degrees +/- 2 degrees C and 86 +/- 3% RH). The MV-678 was tested against the first, second, third and fourth instar larvae. The concentrations used were 0.0032, 0.016, 0.08, 0.4 and 2.0 mg/l. The morphogenetic aberrations were determined and divided into 8 groups, among which they included (1) death larvae, (2) late fourth instar larvae before pupation, (3) larvae with pupae partly emerged, (4) white pupae, (5) brown pupae, (6) elephantoid pupae of which pupae with adults visible inside, (7) pupae with apparently adults partly emerged and (8) death adults. The percentage mortality rates were found to be relatively high in pupal and larval stages when they were treated with 2.0 mg/l. The LC50 values were 0.26, 0.175, 0.06 and 0.032 mg/l for the first, second, third and fourth instar larvae respectively. The effectiveness of MV-678 at 2.0 mg/l was about 11 days under the open air conditions (28 degrees +/- 2 degrees C and 72 +/- 3% RH). When the fourth instar larvae were treated with 0.4 and 2.0 mg/l of MV-678, the LC50 values were 3.1 and 7.1 days respectively. PMID- 4023816 TI - Bioassays of Bacillus sphaericus (strain 1593) against mosquitoes of public health importance in Malaysia. AB - The pathogenicity of Bacillus sphaericus strain 1593 was tested against laboratory-reared larvae of four local species of mosquitoes of public health importance in Malaysia; Aedes aegypti, Anopheles balabacensis, Mansonia uniformis and Culex quinquefasciatus. The bacteria was shake-cultured at 28 +/- 1 degrees C for three days, using Glucose-Yeast Extract Salts medium. After which, the spores and vegetative cells were harvested and stored at 4 degrees C before use. Conditions for bioassays were mean temperature of 25 +/- 1 degrees C and relative humidity 65 +/- 5.0. Twenty third-instar larvae of each species were assayed in 90 ml of diluted spore solution. Each concentration and a control were replicated three times for each bioassay. Larval mortalities at 24 hours and 48 hours were taken and analyzed through Probit Analysis using a computer (IBM 370). LC50 values after 48 hours of exposure showed an increasing order of larval susceptibility as follows: Ae. aegypti (417.70 x 10(4)), An. balabacensis (45.84 x 10(4)), Ma. uniformis (18.23 x 10(4)) and Cx. quinquefasciatus (4.14 x 10(4) spores/ml). With the ability to kill 90% of the Cx. quinquefasciatus larvae tested with just a concentration of 10(5) spores/ml, B. sphaericus (strain 1593) has shown good potential as a biocontrol agent for this species of mosquito. PMID- 4023817 TI - Breeding point and larval association of anopheline mosquitoes of northwest Mindoro, Philippines. AB - A larval survey of stream breeding Anopheles was conducted in the foothills of northwest Mindoro Island, Philippines. Eleven species were collected with An. ludlowae constituting 27.9% of the total. The three malaria vectors in the area, An. flavirostris, An. maculatus and An. mangyanus, made up 25.2, 5.1 and 3.8% of the collection, respectively. Breeding point induces were used to identify optimum habitat and larval association analyses. An. annularis and An. ludlowae had high positive association index with An. flavirostris, while An. mangyanus and An. filipinae appeared to have poor association within the breeding point. PMID- 4023818 TI - Precipitating antibodies to non-treated dengue type 2 viral antigens in sera of Thai hemorrhagic fever patients by crossed immunoelectrophoresis. AB - Crossed immunoelectrophoresis of dengue type 2 virus revealed at least two precipitating antigens which shared some antigenic determinants. Glycoprotein components of both antigens were detected by binding to concanavalin A. Sera from dengue hemorrhagic fever patients showed precipitating antibodies to both antigens which could be quantitated according to the precipitate patterns formed in the intermediate gel of crossed immunoelectrophoresis. All secondary dengue hemorrhagic fever patients demonstrated an increase in precipitin titers in convalescence sera. Most patients with mild illness contained precipitating antibodies in acute phase sera whereas severe cases did not. Convalescent sera from severe cases showed only low titers. These precipitating antibodies may be associated with protection since they were produced early only in those with mild form of illness. PMID- 4023819 TI - Will latent iron deficiency affect the mitochondrial iron-containing enzymes? AB - Since information pertinent to the effect of prelatent or latent iron deficiency on tissue iron is scare, the present study was aimed at producing this stage of iron deficiency in rats by phlebotomy and to determine whether the mitochondrial iron-containing enzymes, succinate dehydrogenase (SDH) and glycerophosphate dehydrogenase (GPDH) were affected. These phlebotomized rats showed a subclinical aneamic picture in the blood together with reduced plasma iron and storage iron in the spleen and liver, but an elevated plasma total iron-binding capacity (TIBC). Under this latent iron deficient state, the SHD in the heart and the skeletal muscle with mixed-fibre types (gastrocnemius and plantaris) but not the red (soleus) and white fibres (vastus lateralis) showed reduced activities. No significant changes in GPDH activities were found in these organs. This finding is consistent with our early report (Quisumbing et al., 1985) that even in mild iron deficiency, some loss of mitochondrial functions could have occurred and this could affect the muscular endurance. SDH was more affected by latent iron deficiency than GPDH. PMID- 4023820 TI - Pseudomonas pseudomallei in southern Thailand. AB - The distribution of Pseudomonas pseudomallei was studied in soil and water from various sources of Songkla province, Southern Thailand. P. pseudomallei was isolated from the surface soil of rubber plantations (60.9%) and from the bottom sediments of rice fields (78.1%). Farmers and plantation workers will have a greater risk of contracting melioidosis. PMID- 4023821 TI - The role of toxoplasmosis in congenital disease in Malaysia. AB - Toxoplasmosis was found not to be an important cause of intrauterine infection in Malaysia as the rate of toxoplasma-specific IgM in 1,060 congenitally defective Malaysian children, 0 to 4 months old (0.4%) was lower than that in 405 normal children of the same age group (2.0%). A total of 8.2 intra-uterine toxoplasmic infections per 1,000 live births was detected of which one-third (2.7 per 1,000 live births) was overt, manifesting symptoms more of liver damage, than eye or brain damage. A comparison was made with the rates in U.S.A. and Europe. The role of toxoplasmosis in abortion needs to be studied. PMID- 4023822 TI - [Survival of patients with liver cirrhosis]. PMID- 4023823 TI - [Characteristics of the clinical course of pheochromocytoma]. PMID- 4023824 TI - [Thermography in arteriosclerosis obliterans of the lower limbs]. PMID- 4023825 TI - [Prevention and treatment of complications of breast endoprostheses]. PMID- 4023826 TI - [Effect of sodium oxybutyrate on the microcirculation of the ischemic hand]. PMID- 4023827 TI - [Compression of cerebral hemispheres in contusion foci]. PMID- 4023828 TI - [Use of organosilicone foam retardants in endoscopic and roentgenological studies]. PMID- 4023829 TI - [Temporal arteritis]. PMID- 4023830 TI - [Prognosis and prevention of suppurative surgical complications]. PMID- 4023831 TI - [Tumor markers in breast cancer]. PMID- 4023832 TI - [Valsalva-Burger test in the evaluation of coronary reserve]. PMID- 4023833 TI - [D-xylose test for determining the absorptive capacity of the ileum]. PMID- 4023834 TI - [Lesions of the neuromuscular system in mechanical jaundice before and after hemosorption]. PMID- 4023835 TI - [Hyperbaric oxygenation in dyscirculatory myelopathies]. PMID- 4023836 TI - [Center for the complex diagnosis of exogenous allergic alveolitis in East Germany]. PMID- 4023837 TI - [Mathematical method of diagnosis and the prevalence of premorbid chronic bronchitis]. PMID- 4023838 TI - [Effectiveness of treatment of peptic ulcer in relation to ambulatory treatment and length of hospital stay]. PMID- 4023839 TI - [Biliary calculi]. PMID- 4023840 TI - [Characteristics of drug-induced anaphylactic shock]. PMID- 4023841 TI - [Graded compression in the treatment of rupture of pubic symphysis]. PMID- 4023842 TI - [Immunostimulators in the complex treatment of acute pneumonia]. PMID- 4023843 TI - [Clinical evaluation of methods of studying gastric acid production]. PMID- 4023844 TI - [Disorders of kidney function in myocardial infarction]. PMID- 4023845 TI - [Pharmacokinetics of isoniazid in patients with pulmonary tuberculosis]. PMID- 4023847 TI - [Measurements of radiation exposure of patients during indirect transvenous digital subtraction angiography--comparison of pulse-mode and continuous-mode operation]. PMID- 4023846 TI - [DSA using fine needle puncture for the elimination of vascular complications in hemodialysis shunts]. PMID- 4023848 TI - [Obstetric roentgen diagnosis and special roentgen diagnosis of the female pelvis]. PMID- 4023850 TI - [Results of radiotherapeutic treatment of malignant tumors of the tongue]. PMID- 4023849 TI - [Iopamidol (Solutrast) in excretory urography]. PMID- 4023851 TI - [Thoracic empyema]. PMID- 4023852 TI - [Reconstructive operations for tracheal stenoses and tracheoesophageal fistulae. II]. PMID- 4023854 TI - [Treatment of perforated gastroduodenal ulcers, particularly in young people]. PMID- 4023853 TI - [Cancer of the cardia]. PMID- 4023855 TI - [Early carcinoma of the stomach]. PMID- 4023856 TI - [Acute blockage of the choledochus and papilla]. PMID- 4023857 TI - [Agenesis of the gallbladder]. PMID- 4023858 TI - [Focal liver disease in the CT image]. PMID- 4023859 TI - [Prophylactic and therapeutic effect of ornidazole (Tiberal Roche) in abdominal surgery]. PMID- 4023860 TI - [Chylangioma of the mesentery as a cause of volvulus of the small intestine]. PMID- 4023861 TI - [Our surgical method for acquired anal incontinence]. PMID- 4023862 TI - [Radiation injuries of the intestines]. PMID- 4023863 TI - [Electric injuries in children]. PMID- 4023864 TI - Extracapsular parotidectomy--a radical operation for selected malignant parotid tumours. PMID- 4023865 TI - Parathyroid disease. Part I. The management of primary hyperparathyroidism. PMID- 4023866 TI - Sterility of the cysterna chyli during reconstructive aortic procedures. PMID- 4023867 TI - Acute pancreatitis. Experience at the Johannesburg Hospital. PMID- 4023868 TI - Pharyngo-oesophageal reconstruction with the pectoralis major myocutaneous flap. PMID- 4023869 TI - The use of indwelling atrial catheters as a method of venous access in paediatric patients. PMID- 4023870 TI - A container for the rapid transfusion of blood and blood products. PMID- 4023871 TI - Idiopathic chronic ulcerative enteritis. A case report. PMID- 4023872 TI - Additives--a hazard of generic substitution. PMID- 4023873 TI - Peritonitis in the immunosuppressed female--possible role of the IUCD. PMID- 4023874 TI - AIDS in Johannesburg. PMID- 4023875 TI - Alcohol abuse and public transport. PMID- 4023876 TI - Threshold for initiation of phototherapy in infants with non-haemolytic hyperbilirubinaemia. AB - The effect of initiating phototherapy at three different bilirubin concentrations in infants with physiological jaundice was studied in 98 clinically jaundiced term infants. Phototherapy was initiated at levels of 170, 257 and 300 mumol/l in groups A, B and C respectively. There was no difference between the groups in terms of days in hospital and bilirubin levels at entry or at exit from the study. Of group A, 97% received phototherapy v. 47% and 18% in groups B and C respectively. Peak bilirubin in those infants in group C receiving phototherapy was 318 mumol/l v. 282 mumol/l and 229 mumol/l in groups A and B. Two group C infants suffered complications of hyperbilirubinaemia. Rebound hyperbilirubinaemia was noted in infants with more severe jaundice after cessation of phototherapy. The threshold for toxicity in non-haemolytic hyperbilirubinaemia may be higher than the still widely accepted 340 mumol/l value, but pending definitive studies phototherapy will continue to be initiated at levels of greater than 257 mumol/l in term infants with hyperbilirubinaemia. PMID- 4023877 TI - [The seasonal incidence of acute appendicitis]. AB - The seasonal incidence of acute appendicitis in a black community is described. This phenomenon is explained and its implications for the aetiology and pathogenesis of this common disease are illustrated. PMID- 4023878 TI - A new multiple sclerosis epidemic? A pilot survey. AB - There may be an increasing incidence of multiple sclerosis in South Africa. All newly-diagnosed white Afrikaans-speaking patients from the Pretoria area were examined over a 12-month period and 5 new cases were diagnosed. This is a highly significant rise over the expected 0,2/100 000/year (P less than 0,001). PMID- 4023879 TI - What do pacemaker recipients think of their implantations? An exploratory study. AB - Interviews conducted with 94 pacemaker recipients were analysed to assess their knowledge and understanding of their disease and treatment, as well as to determine their self-assessment of the quality of life before and after implantation. Many patients knew little about their illness, the reason for having a pacemaker, or their prognosis. Eighteen patients claimed still to be in bad physical condition; 47 patients claimed to be physically handicapped, in 32 of whom the handicaps could be related to their cardiac condition. Fifty patients said that they were less active after implantation than before it. These findings suggest a lack of meaningful patient-doctor/doctor-patient communication. It is suggested that a team approach involving a social worker would improve continuity of care and communication, as well as the quality of patients' lives. PMID- 4023880 TI - The use of the Samson modification of the Mapleson 'A' circuit during blind nasal intubation for anaesthesia. AB - A technique of blind nasal intubation for anaesthesia using the Samson modification of the Mapleson 'A' circuit is described. Adequate depth of anaesthesia is maintained by continuous insufflation, and scavenging is continuously used to remove waste anaesthetic gases. The position of the tube in relation to the larynx is estimated by movement of the reservoir bag and intermittent condensation of expired water vapour in the clear plastic of the circuit. PMID- 4023881 TI - Ethanol content of some pharmaceuticals available in the RSA. AB - The Medicines Control Council is concerned about the influence of the simultaneous ingestion of alcohol and medicines on certain psychomotor functions and the consequent inability of the consumer to perform tasks which require mental clarity. Health care personnel should be aware of the alcohol content of medications when counselling patients receiving drugs against alcoholism or patients who should avoid alcohol. A compilation, short-listed from over 300 ethanol-containing prescription and non-prescription drug products available in the RSA, is presented. PMID- 4023883 TI - Superior dislocation of the hip. A report of 2 cases. AB - Anterior hip dislocation is relatively uncommon and constitutes only 12-18% of all hip dislocations. Of these the rarest type is the superior anterior dislocation; 2 patients are described, the mechanism of injury, management and complications discussed, and the literature reviewed. PMID- 4023882 TI - Autopsy assessment of liver lacerations. A study of 62 cases. AB - The results of 127 consecutive autopsies on victims of motor vehicle, train and tractor accidents were analysed to determine the incidence, extent and severity of liver injury as well as to formulate a method of grading such injuries relevant to forensic autopsy practice. All liver lacerations noted were assigned an injury-assessment index. The features which emerge from the study are as follows: (i) almost 50% of the the victims had liver lacerations; (ii) in almost 75% of these, multiple lacerations were present; and (iii) in over 33% of those with liver lacerations severe liver injury in the form of lobal transection was present. The implementation of injury-assessment indices as a matter of routine in the grading of traumatic lesions at autopsy is suggested. PMID- 4023884 TI - Conservative management of amoebic liver abscess complicated by pericardial extension. A case report. PMID- 4023885 TI - Oral treatment with ketoconazole in systemic candidosis of guinea-pigs: microbiology, hematology and histopathology. AB - Non-pretreated Albino guinea-pigs were infected intravenously with Candida albicans and treated orally either with placebo or ketoconazole. The 17-day follow-up of the fungal dissemination was based upon hematology, on gross and microscopic lesions and on the demonstration of the fungus by culture techniques. The efficacy of ketoconazole, both with regard to the quantity and the morphology of fungi in various organs and the tissue-healing process are discussed. The treatment of human systemic candidosis will also be considered. No side-effects due to the therapy were observed in these experiments. PMID- 4023886 TI - Experimental chronic vaginal candidosis in rats. AB - In the past, the rat model of experimental vaginal candidosis has been used to study the efficacy of antifungal agents in eradicating acute vaginitis. In the present study, chronic vaginal candidosis was induced to study the natural history of the infection. Results indicate that chronic infection is readily achieved and is strictly dependent on oophorectomy and hormonal maintenance of pseudoestrous. Histologic studies confirm that rats so infected and with long term vaginal carriage of Candida albicans have true chronic infection with extensive mycelial formation and superficial mucosal invasion. PMID- 4023887 TI - Molecular and cellular events during the yeast to mycelium transition in Sporothrix schenckii. AB - Unbudded singlets from exponentially growing yeast cells of Sporothrix schenckii were harvested, selected by filtration and allowed to form germ tubes in a basal medium with glucose at pH 4.0 and 25 degrees C. These conditions supported only the development of the mycelial form of S. schenckii in a reproducible manner which allowed further analysis of the early cellular events occurring during the yeast-to-mycelium transition. The relationship between macromolecular synthesis (DNA and RNA synthesis) and nuclear division, hyphal growth and septum formation were investigated during germ tube formation. RNA synthesis started 0 to 3 h after the induction of germ tube formation, followed by DNA synthesis and the first nuclear division, which took place between 3 and 6 h. Germ tube formation followed nuclear division and was first evidenced 6 h after the induction of germ tube formation, but was not completed until 12 h after inoculation. Septation was first observed in these germ tubes at the mother cell-germ tube junction 6 h after induction. Addition of hydroxyurea, an inhibitor of DNA synthesis, to the medium, also inhibited nuclear division and germ tube growth, suggesting that these processes in S. schenckii are dependent upon DNA synthesis. PMID- 4023888 TI - Contribution of complement component C5 to the pathogenesis of experimental murine cryptococcosis. AB - C5-deficient (C5-) mice succumb much sooner after intravenous inoculation with Cryptococcus neoformans than do C5-sufficient (C5+) mice. The C5- mice developed acute, fatal cryptococcal pneumonia, whereas the C5+ mice did not. The pneumonia was characterized by lung viable counts in C5- mice up to 1000-fold higher than in C5+, initial sequestration of twice as much 59Fe-labeled C. neoformans, and subsequent development of pulmonary edema. Chemotaxis of heterophils (PMNs) and mononuclear cells in response to C. neoformans was markedly greater in C5+ mice than in C5- animals. The effect of C5 on localization and growth of C. neoformans in the lung appeared to account for the disparate survival times of C5+ and C5+ mice after intravenous inoculation with C. neoformans. PMID- 4023889 TI - Actuarial status of the OASI and DI Trust Funds. AB - This article summarizes the current financial and actuarial status of the old age, survivors, and disability insurance (OASDI) program, as shown in the 1985 Annual Report of the Board of Trustees. The Trustees note that the combined assets of the OASI and DI programs will be sufficient to pay OASDI benefits on time well into the next century based on all four sets of economic and demographic assumptions. Based on the pessimistic assumptions, the DI program could become unable to pay benefits on time by the end of 1987, but this problem could be prevented by a reallocation of contribution rates between the OASI and DI programs. For the long range--the next 75 years--the Trustees estimate that the OASDI program is in close actuarial balance based on intermediate assumptions -that is, the average annual income rate is estimated to be between 95 percent and 105 percent of the average annual cost rate during that period. The long range actuarial deficit based on the intermediate (Alternative II-B) assumptions represents about 3 percent of the average annual cost rate for the program. PMID- 4023890 TI - The role of the pathologist in the surgical treatment of hyperparathyroidism. AB - Appropriately extensive surgical treatment of hyperparathyroidism depends upon accurate assessment of the extent of disease. We have believed that such assessement is the responsibility of the surgeon because at random biopsy with light microscopy the pathologist may not be able to differentiate adenoma from hyperplasia or even normal from abnormal glands. To test this hypothesis, three pathologists reviewed 50 unlabelled slides of parathyroid tissue and attempted to correlate them with clinical diagnoses which were based upon widely accepted criteria. They were asked to identify each slide as adenoma or hyperplasia, or both, or normal using whatever criteria they wished. A specific diagnosis of adenoma was correct in 35 and 83 per cent of interpretations and of hyperplasia in 38 and 60 per cent of interpretations. The less specific diagnosis of adenoma or hyperplasia (that is, abnormal tissue) was correct in 78 to 100 per cent. A diagnosis of normal was correct in 71 to 78 per cent. Adenoma was most likely confused with hyperplasia; hyperplasia was equally mistaken for adenoma or normal. We conclude that with random, subtotal specimens taken at biopsy (simulating intraoperative conditions) differentiation of adenoma from hyperplasia of the parathyroid gland is poor. Differentiation of normal from abnormal parathyroid tissue also is unreliable. Because the consequences of misdiagnosis are severe, pathologists should not be asked to make specific diagnoses intraoperatively but only to distinguish the parathyroid tissue from the nonparathyroid tissue. PMID- 4023891 TI - Retroperitoneal hematomas of traumatic origin. AB - The significance of retroperitoneal hematomas of traumatic origin ranges from inconsequential to fatal. To elucidate factors determining this significance, 203 such instances were analyzed. In 27 patients in whom operation was not required, the diagnosis was established by roentgenologic studies. In 176, the diagnosis was made at celiotomy; in 67, retroperitoneal hematoma had ruptured into the abdomen and all were explored; the retroperitoneal hematoma was not disturbed in 62 because it appeared contained and not expanding. Due to the location around the pancreatoduodenal region or the strong possibility of injury to a major vessel, 39 contained retroperitoneal hematomas and were explored. Of the 39 deaths observed, 31 occurred in the patients admitted with shock. Twelve deaths were attributed to bleeding from the retroperitoneal hematoma. Retroperitoneal hematomas in patients who are in shock, who have peritoneal irritation or positive peritoneal lavage results, should undergo operation. Those retroperitoneal hematomas found to be contained and not expanding should not be opened, unless it is necessary to exclude associated injuries. Patients with retroperitoneal hematomas who are not in a state of shock and who have negative peritoneal lavage results do not need urgent operation, but require observation. PMID- 4023892 TI - Evaluation of the surgical treatment of chronic calcifying pancreatitis. AB - In the last 20 years, we have observed 264 instances of CCP. Of these, 136 (50.5 per cent) had 171 surgical procedures. Pancreatic calcifications were present in 83.1 per cent of the patients. One hundred and twenty-one were alcoholics (88.9 per cent) and 15 (11.0 per cent) abstained from alcohol. The surgical indications involved clinical uncontrollable pain and organic complications of the disease. The operations performed consisted of 62 wide side to side pancreaticojejunostomies, with loop excluded in Roux-en-Y, 40 pancreatectomies and 69 other operations. The choice of operation depended upon the analysis of each patient. The postoperative period of observation varied from two to 198 months, the average being 56.9 +/- 49.1 months. Thirty-five reoperations were performed for persistence or relapse of pain or the appearance of complications. Immediate post-operative complications and deaths occurred in 44 (25.7 per cent) and in six patients (3.5 per cent), respectively, considering the 71 operations performed. A satisfactory pain relief was evidenced in 61.0 per cent of the patients and total mortality reached 42.6 per cent. When the patients who underwent pancreaticojejunostomy, pancreatectomy and other operations were compared, no significant statistical difference was noticed with regard to the incidence of immediate post-operative complications and deaths, pain relief, appearance of diabetes or steatorrhea and mortality. There was also no significant difference as to the mortality among the alcoholic CCP, calcified or not, and idiopathic CCP (all calcified). On the other hand, the difference was statistically significant concerning the reoperation incidence in the group of patients who underwent the three types of operations mentioned. The longest survival time after pancreaticojejunostomy, pancreatectomy and other operations was 192, 137 and 198 months, respectively. The mean age at the time of death was 44.5 +/- 10.0 years, significantly inferior to the life expectation of the Brazilian male, which is 62 years. The mortality was higher in the first five postoperative years, corresponding to 77.6 per cent of the over-all mortality. There was no significant difference of survival time among the groups of patients undergoing the different types of operations. CCP is an extremely serious disease, progressive in spite of adequate treatment, sensibly diminishing the expectation and quality of lives of those with the condition, often interfering with the activity and productivity of the patient.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 4023893 TI - Prognostic indicators in femoropopliteal and distal bypass grafts. AB - Over a period of six years, 265 femoropopliteal and infrapopliteal bypasses were performed in 243 patients with infrainguinal arterial occlusive disease. The cumulative patency rate for all grafts was 70.9 per cent at one year, 59.3 per cent at three years and 48.5 per cent at five years. Femoropopliteal bypasses showed a significantly better patency rate than femoral infrapopliteal grafts and autogenous vein grafts had a significantly higher patency rate than human umbilical vein grafts. No demonstrable difference in patency rates was shown in patients with and without diabetes. Synchronous proximal and distal revascularization for limb salvage in properly selected patients with multisegmental disease achieved a cumulative patency rate of 100 per cent at two years with no operative deaths. Therefore, this procedure is recommended, but individualization of treatment rather than routine synchronous repair is urged. PMID- 4023894 TI - The frequent occurrence of false-positive results in phleborheography during pregnancy. AB - In this study, none of 25 pregnant women without any past history of venous thromboembolic disease had a positive phleborheogram sometime during their pregnancy or within six weeks post partum. In contrast, zero of ten nonpregnant women, also screened for venous thrombophlebitis, had a positive test finding during the same time interval. No clinical parameters, including weight gain, leg circumference, leg swelling, development of varicose veins, leg pain or use of support stockings, correlated with the occurrence of a positive test result. While there is conflicting evidence from other studies, our data suggest the need for caution in interpreting a positive phleboroheogram as an accurate indicator of thrombophlebitis in pregnant women. PMID- 4023895 TI - Choledochoduodenostomy after previous gastrectomy or duodenal operations. AB - Our results show choledochoduodenostomy to be safe in patients with a Billroth II duodenal stump or any previous duodenal operation with vascular interruption. These results are consistent with our use of choledochoduodenostomy as the preferred technique in all patients with residual stones, a dilated common duct or benign ampullary stenosis. PMID- 4023896 TI - Acute appendicitis in the elderly. AB - A prospective study was done on 104 patients more than 60 years old with appendicitis. The clinical features are by and large, similar to that of the younger patient. However, four patients presented atypically with abdominal distension with little or no pain. A statistically significant increase in appendiceal perforation is found in patients more than 70 years old and in patients with prolonged delay in operation. However, delay on the part of the surgeon contributed only slightly to the high appendiceal perforation as 85.6 per cent of patients who were operated upon within 24 hours of admission. Appendicitis in the elderly patient appeared to progress to perforation faster and perforation occurred in about 40 per cent of patients within 24 hours of onset of symptoms. Five patients died and 29 postoperative complications occurred in 24 more patients. An associated medical disease is linked to a statistically significant increase in mortality. Appendiceal perforation and a total delay of more than 37 hours are associated with a statistically significant increase in morbidity. PMID- 4023897 TI - Safer intraoperative carotid arteriography. AB - A new technique of intraoperative carotid arteriography after endarterectomy is described. Placement under direct vision of a plastic angiocatheter through the superior thyroid artery into the lumen of the common carotid artery facilitates arteriography without the potential complications of puncture of the common carotid artery wall. PMID- 4023898 TI - An electronic technique for compartment pressure measurement using the wick catheter. AB - Compartmental pressure measurement through an electromechanical process can be readily, accurately and inexpensively accomplished with standard hospital equipment. Best results will be obtained when personnel familiar with the set up and continued use of pressure monitoring equipment are assigned for the care and recording of data. The most frequently encountered problems associated with this technique are improper settings or inadequate calibration of pressure monitors and stopcocks or thrombosis of the wick catheter itself. PMID- 4023899 TI - A practical approach to wound care in patients with complex enterocutaneous fistulas. AB - A practical, low cost method for controlling high output enterocutaneous fistulas is presented herein. The technique is advantageous because it provides for excellent protection of the skin, is low in cost and is constructed from readily available materials. It is applicable to all fistulas which do not readily accept prefabricated base plate appliances. Its components are so simple that minimal time for wound care on the part of the surgeon, nursing staff or stomal therapist is required. PMID- 4023900 TI - The anterior approach to control the splenic vessels in distal pancreatectomy. PMID- 4023901 TI - A simple method for identifying and testing the recurrent laryngeal nerve. AB - Simultaneous stimulation of the recurrent laryngeal nerve and palpation of an impulse in the homolateral cricothyroid area was performed upon 20 patients. Electrical stimulation of the recurrent laryngeal nerve with currents of 2 milliamperes caused no postoperative deficits in any of the patients studied. This is a simple and reproducible method to help identify the RLN and to confirm that the recurrent nerve is intact and viable at the completion of a surgical procedure. The technique is simpler than checking cord motion at the conclusion of surgical procedures upon the thyroid or parathyroid glands. Due to the variability of the response in some of the patients, we believe that the procedure should be tried on more patients before it is recommended as a conclusive test. PMID- 4023902 TI - Persistent primitive hypoglossal artery associated with Arnold-Chiari type I malformation. AB - The case of a 49-year-old woman with persistent primitive hypoglossal artery associated with Arnold-Chiari type I malformation is reported. The hypoglossal artery was located on the left side. The left vertebral artery was hypoplastic, the right vertebral artery could not be visualized angiographically. The clinical significance of a persistent primitive hypoglossal artery is discussed. PMID- 4023903 TI - Antiestrogenic therapy of meningiomas--a pilot study. AB - Six patients with inoperable, nonoperative, or recurrent meningiomas were treated with the antiestrogenic agent tamoxifen (Nolvadex) during an 8-12-month period. Computer tomographic, scintigraphic, and clinical evidence of an unspecific tumor response was only encountered in one patient after 4 months of therapy with tamoxifen. The 2-year results did not indicate a favorable response to antiestrogenic treatment. The significance of sex-steroid receptors and their possible prognostic value in endocrine therapy of meningiomas is discussed. PMID- 4023904 TI - Multiple fungal aneurysms: report of a rare case implicating steroid as predisposing factor. AB - A 61-year-old man with a ruptured aneurysm of the anterior communicating artery developed hemorrhagic cerebral infarction 22 days after an operation associated with occlusion of the right angular artery. Angiograms further revealed sequential changes of intracranial vessels including progressive obstructions of the right anterior and middle cerebral arteries and four aneurysms on the left pericallosal artery. Subsequently, the patient became comatose and died. At autopsy the newly formed aneurysms originating from the left pericallosal artery were of fungal (Phycomycetes) origin and numerous nonseptate, branching hyphae were also seen in the obstructed cerebral arteries. Intracranial fungal aneurysms are reviewed in the literature and the pathogenesis in the present case is discussed. PMID- 4023906 TI - Posttraumatic parkinsonism. AB - Development of parkinsonian features following a blunt head injury in a 37-year old man is described. High definition computed tomography scan of the midbrain demonstrated low-density lesions in the region of substantia nigra. PMID- 4023905 TI - Acute bilateral epidural hematoma. AB - A case of acute bilateral epidural hematoma with different onsets is presented. The pathogenesis of the two hematomas is discussed. The importance and the limits of computed tomography scanning in these cases are stressed. PMID- 4023907 TI - Traumatic bilateral epidural hematomas presenting at different times in a patient with large ventricles. AB - In a patient with large ventricles, a huge epidural hematoma of venous origin developed after removal of a contralateral traumatic epidural clot which was produced by the tearing of the middle meningeal artery. The possible pathophysiologic characteristics of such hematomas are discussed. PMID- 4023908 TI - Neurinoma of the oculomotor nerve. AB - A case of intracranial neurinoma with discrete oculomotor nerve palsy and ipsilateral exophthalmos was reported. Review of the literature revealed that oculomotor palsy as the initial symptom may be pathognomonic in the neurinoma originating from the oculomotor nerve. PMID- 4023909 TI - Glossopharyngeal neuralgia with cardiac syncope. A case successfully treated by microvascular decompression. AB - A case of glossopharyngeal neuralgia associated with episodic cardiac arrest and syncope is presented. Posterior fossa exploration showed that the left glossopharyngeal and vagus nerves were compressed by the posterior inferior cerebellar artery. Microvascular decompression resulted in complete relief of glossopharyngeal neuralgia, cardiac syncope, and seizure. The mechanism of glossopharyngeal neuralgia associated with cardiac syncope is discussed. PMID- 4023910 TI - Aneurysms associated with fenestrated anterior cerebral arteries. Report of four cases and review of the literature. AB - Four cases of aneurysms associated with a fenestrated anterior cerebral artery are presented. The combination of aneurysms and fenestration of the anterior cerebral artery is rare, and nine cases including ours have been reported. In all cases fenestrations were found within the distal two-thirds of the horizontal portion of the anterior cerebral artery. It may be presumed that fenestration of the anterior cerebral artery is the remnant of the plexiform anastomosis in the fetal stage, especially between the anterior cerebral artery and the primitive olfactory artery. PMID- 4023911 TI - Traumatic homonymous hemianopsia associated with a juxtasellar hematoma after acute closed head injury. AB - A case is reported in which homonymous hemianopsia associated with a juxtasellar hematoma occurred as a result of an acute closed head injury. The homonymous hemianopsia, which was considerably improved with conservative therapy, is suggested to have been due to vascular insufficiency or edema, or both in the region of the optic tract. PMID- 4023912 TI - Microsurgical anatomy of the region of the foramen magnum. AB - The anatomy needed to plan microoperative approaches to the region of the foramen magnum was examined in 25 cadaveric heads. The structures examined included the lower cranial and upper spinal nerves, the caudal brain stem and rostral spinal cord, the vertebral artery and its branches, the veins and dural sinuses at the craniovertebral junction, and the ligaments and muscles uniting the atlas, axis, and occipital bone. The transoral, transpalatal, labiomandibular, glossolabiomandibular, transsphenoidal, transcranial-transbasal, transcervical, and suboccipital operative approaches to the region are also reviewed. PMID- 4023913 TI - Presidential address: the cost of academic citizenship. PMID- 4023914 TI - Inhibition of human neuroblastoma by dopamine antagonists. AB - The effects of dopamine agonists and antagonists were investigated in human neuroblastoma (HNB) tissue culture cell lines and correlated with the presence of specific membrane-bound dopamine-binding activity ("receptor"). In four HNB cell lines the dopamine antagonists domperidone, pimozide, and spiroperidol inhibited macromolecular synthesis in vitro as indicated by decreased 3H-TdR and 14C-leu incorporation in a dose-response fashion with at least 50% inhibition noted at 10(-6)M concentration of each drug. Dopamine agonists showed no significant inhibition. Scatchard analysis of competitive dopamine-binding assays in all four HNB cell lines and in five of eight solid tumors obtained at surgery demonstrated high affinity, limited-capacity binding consistent with a single class of receptor sites with receptor concentrations (Rc) ranging from 8.8 to 26.7 pmol/gm wet weight of tissue with dissociation constants (KD) from 0.40 to 6.6 nmol/L, compared with a mean Rc of 28.1 +/- 5.2 pmol/gm wet weight of tissue and KD = 0.38 +/- 0.09 nmol/L in receptor-rich dog caudate nucleus, the normal dopamine sensitive control. Survival was prolonged after inoculation of the SK-N-AS cell line into nude mice and subsequent domperidone administration by 50% (24 days after drug initiation versus 16 days in control mice). These data demonstrate inhibition of macromolecular synthesis in HNB by dopamine antagonists and suggest that dopamine receptor is associated with this inhibition. The determination of dopamine receptors may prove useful in the selection of dopamine antagonists as specific chemotherapy for patients with neuroblastoma. PMID- 4023916 TI - Epithelial lining methods in esophageal repair: a comparative study using pedicle flaps in cats. AB - Methods of restoring luminal lining in repair of partial-circumferential esophageal defects were evaluated to compare incidences of strictures and fistulas and quality of surface lining. In cats 50% and 67% circumferential esophageal defects were repaired by direct closure or pedicle flaps (latissimus dorsi) that were unlined (lining restored by epithelialization from wound margins) or that carried lining of normal skin (myocutaneous flaps), skin grafts, or mucosal grafts. Repairs were evaluated for esophagocutaneous fistulas, luminal stricture, flap luminal surface area, and quality of epithelial surface 6 weeks after surgery. Direct closure of 50% circumferential defects was as satisfactory as any flap repair method. Direct closure of 67% circumferential defects caused high incidences of fistulas and strictures, which were lessened by flap reconstructions. Among flap lining methods, normal skin (myocutaneous flaps) gave the lowest incidence of fistulas and strictures and the highest surface quality, but a high incidence of skin paddle loss occurred in this model. Split-thickness epithelial grafts were nearly as satisfactory as myocutaneous flaps, and less lining loss occurred. Epithelialization of unlined flaps gave the poorest results since lining was thin and often incomplete, and wound contraction produced loss of surface area and strictures. The findings are discussed from a perspective of wound healing physiology, and implications for clinical application are presented. PMID- 4023915 TI - Monoclonal antibodies in human renal cell carcinoma and their use in radioimmune localization and therapy of tumor xenografts. AB - A series of monoclonal antibodies (Mabs) to human renal cell carcinoma (RCC) material was developed. Two Mabs (D5D and A6H) that showed especially restrictive reactivities were radiolabeled with iodine 131 and tested in nude mice bearing human tumor xenografts for their ability to specifically localize RCC. Extensive studies of tissue radioactive uptake indicated that these Mabs could specifically localize RCC tumors with some mice achieving high tumor:blood ratios ranging from 15 to 60. Scintigraphic scanning revealed specific and consistent detection of RCC xenografts. Finally, preliminary results indicate that larger intravenous doses of radiolabeled RCC Mabs were effective as radioimmune therapy in inhibiting RCC xenograft growth. Mabs can be produced that are highly restrictive to human RCC and may be useful clinically for radioimmunoscintigraphy or therapy. PMID- 4023917 TI - Effect of 16,16-dimethyl prostaglandin E2 on gastric epithelial cell membrane potentials and resistances. AB - Intracellular microelectrode techniques were employed to examine the effects of 16,16-dimethyl prostaglandin E2 (dmPGE2) on Necturus antral mucosa epithelial cell membrane potentials and resistances. Necturus antral mucosa was mounted in a modified Ussing chamber and stable intracellular impalements were obtained. Addition of 0.01 microgram/ml dmPGE2 to the mucosal solution produced an increase of the apical cell membrane potential (Vmc) from -44.3 +/- 3.1 to -53.5 +/- 3.8 mV (p less than 0.001) and of the basolateral cell membrane potential (Vcs) from 48.8 +/- 2.8 to -57.7 +/- 3.2 mV (p less than 0.001). This reversible, dose dependent hyperpolarization of both cell membranes was accompanied by a decrease in the electrical resistance of the apical membranes (Ra) from 2550 +/- 250 omega/cm2 to 1870 +/- 210 omega/cm2 (p less than 0.05) and a decrease in the resistance of the basolateral membrane (Rb) from 1020 +/- 250 omega/cm2 to 630 +/ 80 omega/cm2 (p less than 0.05). In addition, there was an increase in the resistance of the shunt (intercellular junction, Rs), the major route of transepithelial ion flow, from 710 +/- 60 omega/cm2 to 750 +/- 80 omega/cm2 (p less than 0.05). Thus dmPGE2 increased the cell membrane potentials and reduced the ionic permeability of the intercellular junction. PMID- 4023918 TI - Comparison of gastric mucosal blood flow as measured by H2 gas clearance and microspheres during secretory stimulation and inhibition. AB - H2 clearance is a recently described method of measuring gastric mucosal blood flow that has great potential for clinical use. However, the effects of luminal pH and of secretory activity of the gastric mucosa on the accuracy of H2 clearance measurements have not been systematically examined. We therefore tested the validity of H2 clearance measurements at different pHs in both in vitro and in vivo systems. In addition, we compared measurements by H2 clearance and radioactive microspheres during stimulation and suppression of acid secretion. In vitro, H2 washout was relatively constant over a range of pHs from 2.0 to 8.0. In chambered segments of canine fundus in vivo, H2 clearance was not significantly affected by pH of the luminal solutions either in the resting state or at lower blood flows induced during infusion of vasopressin. Finally, there was a close correlation (r = 0.85; p less than 0.001) between H2 clearance and microsphere measurements under resting conditions, during intravenous histamine stimulation, and after infusion of cimetidine to suppress acid secretion. In summary, H2 clearance reliably and accurately measures gastric mucosal blood flow at different luminal pHs and under conditions that stimulate or suppress acid secretion. PMID- 4023919 TI - Decreased wound neutrophils and indiscrete margination in the pathogenesis of wound infection. AB - To assess the pathogenesis of increased susceptibility to infection and septic death in a rat model, neutrophils (PMNs) in the wound, circulating PMNs, and their in vivo activity were evaluated after 30% and 60% burns. Eight hours after injury there were twice as many PMNs in the wounds of rats that sustained 30% compared with 60% burns. There was no difference between these two groups in the number of circulating PMNs at 2, 4, 6, and 8 hours after injury. In vivo evaluation of PMN response to infusion of F-Met-Leu-Phe revealed that circulating PMNs were more sensitive 4 hours after 60% burns compared with sham burns. At this time PMNs were found to be less sensitive to zymosan-activated serum infusion after 30% burns compared with sham burns. However, the PMNs in rats with 30% burns were more sensitive to this stimulus than were PMNs in rats with 60% injuries. Thus rats with greater injury, known to be more susceptible to wound infection, have fewer PMNs in their wounds 8 hours after injury. This is preceded by an increased sensitivity of PMNs in vivo to bacterial chemotactic factor and a relative increase in sensitivity to wound factors. This unusual finding implicates indiscrete margination as a factor in the pathogenesis of infection. PMID- 4023920 TI - Importance of the ileum in neurotensin released by fat. AB - Neurotensin is a potent stimulant of pancreatic exocrine secretion. Ileal mucosa is the storage site for about 90% of total neurotensin. Release occurs rapidly after a fatty meal and during perfusion of the duodenum and jejunum with fat but not during perfusion of the ileum with fat. To determine the origin of neurotensin released after fat stimulation, we studied the pattern of release of neurotensin before and after resection of the distal two thirds of the small bowel. Six dogs with gastric and duodenal fistulas were studied on different days. All dogs received infusions (in random order) of intraduodenal corn oil (Lipomul) (3 ml/kg/hr) and intravenous calcium chloride (0.36 mmol/kg intravenous bolus, followed by 0.36 mmol/kg/hr infusion) before and 6 weeks after resection of the distal two thirds of the small bowel with preservation of the ileocecal valve. Plasma levels of neurotensin were measured by specific radioimmunoassay. We found that release of neurotensin, in response to both intraduodenal Lipomul and intravenous calcium chloride stimulation, was abolished by resection of the distal small bowel. Before surgery, Lipomul-stimulated release of neurotensin rose to a peak concentration of 51 +/- 17 pg/ml at 30 minutes. After surgery there was no release (the levels were unchanged from basal). Before surgery, intravenous calcium chloride produced a peak release of neurotensin (52 +/- 15 pg/ml) 2 minutes after bolus injection. After surgery, neurotensin was not released by intravenous calcium. We conclude that the source of neurotensin released by perfusion of the proximal gut and by intravenous calcium infusion is the ileum. The release of neurotensin from the distal gut appears to be dependent on a signal from proximal to distal gut. The identity of the signal is unknown but is either a nerve reflex or a peptide agent. PMID- 4023921 TI - Surgical sympathectomy increases pancreatic polypeptide response to food. AB - Numerous studies in man and animals suggest that beta-adrenergic receptors stimulate pancreatic polypeptide (PP) release whereas alpha-adrenergic receptors inhibit PP release. This study was undertaken to further clarify the role of the adrenergic nervous system in regulating PP release. We evaluated the effects of stellatectomy and celiacectomy on resting and meat meal-stimulated PP release in the dog. PP release was studied in three stages--control, poststellatectomy, and poststellatectomy plus celiacectomy in five dogs. The meat meal caused a prompt and prolonged increase in plasma levels of PP. Stellatectomy did not alter the control PP response. However, celiacectomy increased basal and peak PP levels and enhanced the early and late phases of delta-integrated PP release. The data suggest that the celiac and superior mesenteric ganglia are the main source of the adrenergic innervation of the pancreas and that this innervation is primarily an inhibitor of PP release. PMID- 4023922 TI - Protein synthesis in the tumor-influenced hepatocyte. AB - Total body protein turnover is elevated in the Fischer 344 rat bearing a subcutaneous transplantable methylcholanthrene-induced sarcoma. To assess the contribution of the liver, we have measured protein synthesis by hepatocytes freshly isolated from tumor-bearing animals over a range of tumor burdens and from sham-inoculated nontumor bearers. Synthetic rates of total hepatocyte protein were more than twofold greater in hepatocytes from tumor-bearing animals (P less than 0.005) and the increase was proportional to the tumor burden in individual animals (n = 19; r = 0.68; p less than 0.005). When compared with pair fed nontumor bearers, the differences in rates of total hepatocyte protein synthesis reached statistical significance only when the tumor burden exceeded 5% of total body weight. The stimulation in synthetic rates applied equally to secretory and nonsecretory hepatocyte protein. Furthermore, a lack of net protein accrual in the livers of tumor-bearing animals suggests a concomitant increase in the rate of hepatic protein degradation. PMID- 4023923 TI - Declining role of frozen section in surgical planning for thyroid nodules. AB - Needle biopsy (Bx) is superior to clinical selection of thyroid nodules for surgery. Is it superior to frozen section (FS) for surgical planning? Comparison of accuracy of the two procedures was made for 359 patients who underwent both procedures. Bx diagnoses consistent with a low risk of cancer predict a benign lesion at surgery with 90% accuracy. FS on the same patients was also 90% reliable in identifying benign or malignant nodules. Bx diagnoses consistent with a high risk of cancer predict a malignant lesion at surgery with 91% accuracy. FS on the same patients identified only 70% of the cancers. However, false positive diagnoses of cancer were less by FS. Bx diagnoses on nodules with an intermediate risk of cancer (32% to 43%) were insufficiently sensitive for reliable surgical planning. FS on the same nodules was also unreliable. Only three of 359 FS diagnoses contributed decisively to surgical planning. Reliance on Bx could eliminate as many as 99% of FSs. PMID- 4023924 TI - Portacaval shunt in the treatment of primary Budd-Chiari syndrome. AB - We have performed a side-to-side portacaval shunt as the treatment of choice in six cases of primary Budd-Chiari syndrome. All the patients (three men and three women, mean age 33 years) had marked hepatomegaly and massive ascites. Four patients had endoscopically proved esophageal varices with no episodes of bleeding. Preoperative angiographic studies, caval pressure measurement, laparoscopy, liver biopsy specimens, liver scanning, and liver function tests confirmed the diagnosis. A possible etiologic factor was evident in only two cases. A plain side-to-side portacaval shunt was performed in four patients, while two required the interposition of a graft. One patient died after surgery of hepatorenal syndrome. Four of the surviving patients are free of ascites and doing well at 29, 27, 25, and 6 months. The remaining patient subsequently developed cirrhosis and died 76 months after surgery. None of the patients who survived developed encephalopathy. Shunt patency was confirmed endoscopically by variceal decompression in the four patients with esophageal varices. We believe the side-to-side portacaval shunt is a reliable and effective procedure for the definitive management of primary budd-Chiari syndrome. PMID- 4023925 TI - Herpes simplex burn wound infections: epidemiology of a case cluster and responses to acyclovir therapy. AB - Nosocomial transmission of herpes simplex virus (HSV) has been described in intensive care units. A cluster of three patients with HSV wound infections within a 6-week period prompted temporary closure of a burn unit and suggested nosocomial cross infection. However, restriction endonuclease "fingerprint" analysis of the HSV isolates showed them to be genetically and therefore epidemiologically unrelated. This report describes these cases and the use of intravenous acyclovir in the treatment of HSV burn wound infections. PMID- 4023926 TI - Contribution of circulating formed elements to prostanoid production in complement-mediated lung injury in sheep. AB - Incubation of plasma with zymosan results in complement activation. Infusion of this "zymosan-activated plasma" (ZAP) into the superior vena cava in sheep results in pulmonary leukostasis, pulmonary hypertension with generation of thromboxane (TXB), and hypoxemia. To examine the contribution of circulating formed elements to TXB generated when ZAP is infused, we studied four pairs of sheep in a cross-circulation model. Acetylsalicylic acid (ASA) irreversibly acetylates cyclooxygenase and blocks TXB production. Four hours after an intravenous dose of ASA (10 mg/kg), no circulating ASA was detectable by high pressure liquid chromatography. Infusion of ZAP in ASA-treated animals resulted in no pulmonary hypertension and no rise in serum TXB levels. Treated animals were then cross-circulated with untreated sheep through cannulas that attached a carotid artery of each animal to a jugular vein of the other, creating simultaneous arteriovenous fistulas between the animals. A roller pump maintained cross-circulation flow at 450 ml/min for 15 minutes. This resulted in greater than 80% mixing of the circulating blood volumes of each pair of animals, verified by measurement of an intravascular marker. After cross-circulation the ASA-treated animals were still unable to generate TXB in response to ZAP infusion. Untreated animals had a typical response when infused with ZAP after cross-circulation, with elaboration of large amounts of TXB. Since the treated animals with circulating, nonaspirinated formed elements showed no response and the untreated animals with similar blood composition had a normal response, we conclude that circulating formed elements do not contribute significantly to the TXB recovered from sheep infused with activated complement components. PMID- 4023927 TI - Injection corrosion technique. PMID- 4023928 TI - [Irradiation of lymphogranulomatosis patients with large fields of complex configuration, calculating absorbed doses by microcomputer]. AB - The authors demonstrated advantages of irradiating lymphogranulomatosis patients with large fields of complex configuration. The use of computer eliminates the difficulties of dosage calculation. Application for these purposes of the 15 VUMS 28 unit based on the microcomputer "Elektronika-60" is suggested. Algorithm of the dosage calculation program is presented. The program is drawn up according to the GOST so that it can be used by other institutions concerned. PMID- 4023929 TI - [Age-related aspects of intensive therapy of acute poisoning of chemical etiology]. AB - Assay of the clinical course of poisoning with acetic acid, dichloroethane, carbophos, chlorophos, phenobarbital and sodium etaminal in 2538 patients made it possible to define, with the use of the probit analysis, the 25, 50, 75 and 95% concentration thresholds of the lethality in acute poisonings with acetic acid, carbophos and dichloroethane. It was established that under exposure to the toxic substances undergoing different chemical changes in the body, the increase of the lethality risk varied in different age groups. The differences in the structure of outcomes in patients of different age groups formed the basis for making up a classification of the toxicity of the chemical compounds. The differences revealed require a differential approach to the determination of the scope of intensive care of poisonings in terms of the age-associated features. PMID- 4023930 TI - [Croup in toxic forms of diphtheria in adults]. AB - Toxic patterns of diphtheria of the fauces in adults are characterized by laryngeal lesions which considerably deteriorate the disease prognosis. The clinical manifestations of diphtheric croup may be unpronounced in such cases and be masked by other severe disease symptoms. If patients with toxic diphtheria develop croup, the necessity of surgical treatment arises at earlier times as compared with cases of isolated croup. PMID- 4023931 TI - [Autoimmune reactions of the humoral type in viral hepatitis]. AB - Antibodies against antigens of hepatocyte cell membranes are formed in half the patients with hepatitis A and B in one-third of those with pseudotuberculosis. They occur in the period preceding the patients' convalescence rather than in the acute stage of the disease. The recovery of hepatitis patients in whom liver antibodies formed ensued significantly more rapidly than in persons with no autoantibodies. Antibodies against antigens of hepatocyte cell membranes were detectable in different clinical disease patterns. They did not influence the disease progress and witnessed hepatocyte injuries not only in the icteric but also in scarlatiniform and and abdominal disease patterns. PMID- 4023932 TI - [Isoenzymes in patients with protracted viral hepatitis and their significance in the clinical course of the disease]. PMID- 4023933 TI - [Corinfar in the treatment of Raynaud's syndrome in systemic scleroderma (preliminary results)]. AB - Twenty patients with systemic scleroderma (SSD) and Raynaud's syndrome (RS) received 30-80 mg of corinfar, a blocker of calcium channels, during 14 days. Seventeen patients responded to the treatment. The clinical effect was manifested by a decrease in the rate, duration and intensity of RS attacks. Side effects were recorded in 6 patients, but the drug was discontinued only in 2 patients because of the allergic reactions. During treatment, the patients showed an increase in tissue blood flow parameters. Corinfar may be regarded a drug of choice in the treatment of marked RS in SSD. PMID- 4023935 TI - [Various prognoses of possible medical consequences of using nuclear weapons]. PMID- 4023934 TI - [Infarction-pneumonia in acute allergic reaction to levomycetin]. PMID- 4023936 TI - [Secondary pneumonia--an old and new problem]. PMID- 4023937 TI - [Current principles of development of emergency therapy]. PMID- 4023938 TI - [Characteristics of the clinical course and therapy of status asthmaticus]. AB - The increase in the incidence of the status asthmaticus seen over the last years is caused by the growth of the prevalence and a graver course of bronchial asthma. In each specific case, the therapy should be strictly individualized and rest on the dynamic evaluation of the cardiorespiratory system. The majority of patients with a history of the status asthmaticus show a tendency toward its recurrence. The dispensary follow up of patients by means of the allergological rooms plays an important role in the prevention of the development of the status asthmaticus. The clinical manifestations of the status asthmaticus depend to a considerable degree on the previously applied treatment. PMID- 4023939 TI - [Bronchial asthma as a form of pathological adaptation to a microsocial environment]. PMID- 4023940 TI - [Comparative evaluation of various methods of immunosuppressive therapy in severe bronchial asthma]. AB - Altogether 216 patients with grave infection-dependent (49.5%) and autoimmune (50.5%) bronchial asthma received 311 courses of immunosuppressant therapy, with follow up periods up to 8 years. According to the clinico-immunologic data the patients were distributed into 4 groups. The basic drugs were (1) azathioprin, (2) azathioprin and prednisolone, (3) prednisolone, (4) delagil combined with heparin and epsilon-aminocaproic acid. Evaluation of the sort-term results of the treatment showed that the highest percentage of a clinical remission was attained with basic therapy including azathioprin combined with delagil and heparin. The immunosuppressants produced side effects in 14.2-31.3% of patients. These effects (dyspepsia, cytopenia, allergy) were of transitory nature. The long-term results were worse as compared with the short-term ones. The lethality for the whole group of patients amounted to 10.1%. It was caused by the status asthmaticus and cardiopulmonary insufficiency. Indications and contraindications for use of immunosuppressant therapy are provided. PMID- 4023941 TI - [Dynamics of blood fibronectin level in myocardial infarction]. AB - The fibronectin level in the blood of patients with myocardial infarction was measured at varying times from the onset of an angina pectoris attack in order to elucidate the diagnostic importance of blood fibronectin. At the same time these patients were examined over time for the blood content of myoglobin, MB creatine kinase protein and C-reactive protein playing a well-known role in the diagnosis. The blood concentrations of these substances reached the maximal values at different times of myocardial infarction. The mean concentrations of fibronectin in the blood of patients with myocardial infarction ranged within normal starting from the first till the 28th day since the onset of an angina pectoris attack. Moreover, the mean blood fibronectin level in myocardial infarction patients did not differ within the first-third days since the disease onset from that in patients with a clinical picture of unstable angina pectoris which was not accompanied by the development of myocardial infarction. Based on the data obtained it is concluded that measurement of blood fibronectin level does not play any diagnostic role in myocardial infarction. On the other hand, progressive increase in blood fibronectin level throughout 4 weeks starting from the 3d day of the disease and a significantly higher fibronectin content on the 28th day as compared with that on the 3d day is likely to mirror the activity of repair processes occurring in the myocardium. PMID- 4023942 TI - [Knowledge of internal diseases in the wounded--a major achievement of Soviet internists during World War II]. PMID- 4023943 TI - [Lipid peroxidation in the evaluation of healing of myocardial infarction]. AB - The authors studied the time-course of lipid peroxidation with special reference to malonic dialdehyde in blood serum comparatively to the time-course of uricemia in 189 patients with acute large-focal myocardial infarction. It was established that the time-course of malonic aldehyde and uric acid is characterized by a consistent increase which reaches the maximal values at the height of the destructive phase of myocardial infarction as well as by the differences in uncomplicated and complicated healing. The joint index of destruction was developed, permitting one to compare the concentrations of malonic dialdehyde and uric acid in blood serum and to exercise an efficacious biochemical "tracing" of the healing. PMID- 4023944 TI - [Utilization of active forms of oxygen and lipoperoxides in the blood of patients with myocardial infarction]. PMID- 4023945 TI - [Retrospective evaluation of indicators of cardiospecific blood isoenzyme activity in patients with stenocardia and primary and recurrent myocardial infarction]. AB - Comparatively moderate blood fermentemia (KPK, AST, KPK-MB and LDH1) exceeding the level of the statistic M + 1S index in the control group and lasting over 3 to 7 days can be viewed as one of the diagnostic criteria of the preinfarction state. The lack of the correlation between the enzymatic characteristics and the data on blood myoglobin concentration and precordial cartography readings (ECG 35 leads) makes the use of the latter two methods more preferable in the evaluation of the area of necrosis in patients with repeated myocardial infarctions and requires a more careful approach to the prognosis of complications in this patients' group. PMID- 4023946 TI - [Determining the area of myocardial damage by the method of sectorial scanning and its value for prognosis of the outcome of acute myocardial infarction]. AB - The authors describe a method for measuring the myocardial injury area, and show the prognostic value of the latter based on examination of 100 patients admitted to the Cardioresuscitation Department with a diagnosis of acute transmural or large-focal myocardial infarction. The lifetime evaluation data of the IM size by means of two-dimensional echocardiography were in a good agreement (r = 0.85) with the morbid anatomy data. Determination of the injury size and ejection was found to be the most informative method for predicting an outcome of acute myocardial infarction. The use of the different combinations of the prognostic signs expands the possibilities of the given method and makes it possible to screen patients with a high risk of a lethal outcome and development of complications on the basis of the primary care at the early disease stage. PMID- 4023947 TI - [Rupture of the interventricular septum associated with myocardial infarction of the left and right ventricles]. AB - Based on observation over 7 patients with interventricular septum rupture associated with myocardial infarction of the left and right ventricles the authors assume a pathogenetic relationship between interventricular septum rupture and right ventricle involvement into the process. The dependence between the disease prognosis and right ventricle function is discussed. PMID- 4023948 TI - [Evaluation of myocardial reserve in patients with post-infarction heart aneurysm]. AB - The author examined 22 patients with postinfarction heart aneurysm to evaluate the myocardial reserves of the preserved myocardium with the use of the strophanthine test. The time-course of changes in the central hemodynamics, contractile function and segmental myocardial contractility of the left ventricle was evaluated. It was disclosed that the positive inotropic effect of strophanthine depends on the degree of the atherosclerotic lesions of the coronary arteries supplying blood to the zone of the preserved myocardium. In patients with postinfarction heart aneurysm and multiple demonstrable lesions of the coronary artery, administration of strophanthine brought about the deterioration of myocardial contractility of the left ventricle. No relationship was found between the initial status of the hemodynamics and the inotropic effect of strophanthine. PMID- 4023949 TI - [Analysis of the structure of cardiac rhythm in atrial flutter]. AB - Heart rhythm was studied by computer in 67 patients with atrial flutter of different etiology. It was discovered that respiratory activity has an influence on the conduction of atrial flutter waves to the ventricles. In the majority of cases, the conduction of atrial waves to the ventricles is multiple with a constant conduction ratio. However, in some cases the conduction of atrial flutter waves via the atrioventricular system occurs according to the Samoilov Wenckebach periodicals. In the latter case and in atrial flutter with a conduction ratio of 4:1, one-third of patients manifest, after the recovery of the sinus rhythm, atrioventricular blockade, grade 1. PMID- 4023950 TI - Coevolution of competing species: ecological character displacement. AB - Character displacement of competing species is studied. A model, originally developed by MacArthur and Levins (Proc. Natl. Acad. Sci. USA 51 (1964), 1207 1210) and further analyzed by Lawlor and Maynard Smith (Amer. Nat. 110 (1976), 70 99), has been reanalyzed. In the present paper, a more formally correct analysis of the MacArthur-Levins model is provided. A standard population genetics approach to sexually reproducing populations is adopted. The same conclusion as proposed by Lawlor and Maynard Smith emerges; competition can lead only to character divergence. In our analysis we either require that allopatrically evolved consumer populations must be able to coexist at an ecologically stable equilibrium (hence, we require mutual invasibility), or consider the feasibility of allopatric equilibria. PMID- 4023951 TI - Confidence intervals for demographic projections based on products of random matrices. AB - This work is concerned with the growth of age-structured populations whose vital rates vary stochastically in time and with the provision of confidence intervals. In this paper a model Yt + 1(omega) = Xt + 1(omega) Yt(omega) is considered, where Yt is the (column) vector of the numbers of individuals in each age class at time t, X is a matrix of vital rates, and omega refers to a particular realization of the process that produces the vital rates. It is assumed that (Xi) is a stationary sequence of random matrices with nonnegative elements and that there is an integer n0 such that any product Xj + n0...Xj + 1Xj has all its elements positive with probability one. Then, under mild additional conditions, strong laws of large numbers and central limit results are obtained for the logarithms of the components of Yt. Large-sample estimators of the parameters in these limit results are derived. From these, confidence intervals on population growth and growth rates can be constructed. Various finite-sample estimators are studied numerically. The estimators are then used to study the growth of the striped bass population breeding in the Potomac River of the eastern United States. PMID- 4023952 TI - Mortality and aging in a heterogeneous population: a stochastic process model with observed and unobserved variables. AB - Various multivariate stochastic process models have been developed to represent human physiological aging and mortality. These efforts are extended by considering the effects of observed and unobserved state variables on the age trajectory of physiological parameters. This is done by deriving the Kolmogorov Fokker-Planck equations describing the distribution of the unobserved state variables conditional on the history of the observed state variables. Given some assumptions, it is proved that the distribution is Gaussian. Strategies for estimating the parameters of the distribution are suggested based on an extension of the theory of Kalman filters to include systematic mortality selection. Various empirical applications of the model to studies of human aging and mortality as well as to other types of "failure" processes in heterogeneous populations are discussed. PMID- 4023953 TI - The effect of long time delays in predator-prey systems. AB - Past studies have indicated that a time delay longer than the natural period of a system will generally cause instability; however here it is shown that including long maturational time delays in a general predator-prey model need not have this effect. In each of the three cases studied (a predator delay, a prey delay, and both), local stability can persevere despite the presence of arbitrarily long time delays. This perseverence depends upon an interaction between delayed and undelayed features of the model. Delayed processes always act to destabilize the model. For example, prey self-regulation, usually a source of stability, becomes destabilizing if subject to a long delay. However, the effect of such a delay is offset by undelayed regulatory processes, such as a stabilizing functional response. In addition, the adverse effects of delayed predator recruitment can be reduced by the nonreproductive component of the numerical response, a feature not usually involved in determining stability. Finally, it is shown that long time delays are not necessarily more disruptive than short delays; it cannot be assumed that lengthening a time delay progressively reduces stability. PMID- 4023954 TI - The interaction of genetic drift and mutation with selection in a fluctuating environment. AB - The interaction of genetic drift, mutation, and selection in a random environment is investigated using an asymptotic analysis based on assumptions of weak mutation and strong selection. It is shown that genetic drift can be a potent force for removing variation from the population when the random environment tends to occasionally push alleles down to low frequencies. PMID- 4023955 TI - Philosophy of medicine in the Netherlands. PMID- 4023956 TI - The philosophy of medicine in Europe: challenges for the future. PMID- 4023957 TI - Philosophy of medicine in the Federal Republic of Germany (1945-1984). PMID- 4023958 TI - Philosophy of medicine in Scandinavia. PMID- 4023959 TI - Philosophy of medicine in Austria. PMID- 4023960 TI - Prevention of admission and continuity of care. PMID- 4023961 TI - [Infections of the hand--epidemiology]. PMID- 4023962 TI - [Infections of the hand--from the viewpoint of National Swiss Accident Insurance]. PMID- 4023963 TI - [Fungal infections of the hand]. PMID- 4023964 TI - [Rare infections in hand surgery--with the exception of mycoses and parasitoses]. PMID- 4023965 TI - [Acute suppurative infections of the hand--clinical examination technic and therapeutic indications]. PMID- 4023966 TI - [Infections of the hand--principles of general surgical technic]. PMID- 4023967 TI - [Antibiotic therapy and preventive measures against rabies and tetanus in infections of the hand]. PMID- 4023968 TI - [Principles of follow-up care in finger infections]. PMID- 4023969 TI - [Wound infection after blunt, ragged-edged hand injuries--risk of functional impairment, prevention]. PMID- 4023970 TI - [Indications for determining the plasma level of 25-hydroxy-vitamin D]. PMID- 4023971 TI - [Treatment of hypercalcemia]. PMID- 4023972 TI - [Practical approach to renal lithiasis--diagnostic and therapeutic aspects]. PMID- 4023973 TI - Contaminated humidifiers and the lung. PMID- 4023974 TI - Occupational asthma in a factory with a contaminated humidifier. AB - Thirty five printers who had work related wheeze, chest tightness, or breathlessness kept two hourly records of their peak expiratory flow for at least two weeks. They all worked in a factory supplied by air from contaminated humidifiers. The peak flow records showed consistent work related deterioration in 15 workers, nine of whom had a diurnal variation in peak flow exceeding 20%. Ten workers kept further records after the humidifiers had been cleaned, other work practices remaining unchanged. There was substantial improvement in all 10 workers, implying that material from the contaminated humidifier was the cause of the work related changes in peak flow. The patterns of work related changes in peak flow fell into four groups: falls maximal on the first work day, falls maximal midweek, falls equivalent each work day, and falls progressive throughout the working week. Three quarters of this last group had immediate prick test responses to humidifier antigen, which were negative in all the others with work related changes in peak flow. This suggests that the progressive daily deterioration pattern alone is due to an IgE mediated response to humidifier antigens. A large range of microorganisms was identified in the humidifiers. No single microorganism appeared to be the antigen responsible for the precipitating antibody seen in 75% of the study population. PMID- 4023975 TI - Occupational asthma due to formaldehyde. AB - Bronchial provocation studies on 15 workers occupationally exposed to formaldehyde are described. The results show that formaldehyde exposure can cause asthmatic reactions, and suggest that these are sometimes due to hypersensitivity and sometimes to a direct irritant effect. Three workers had classical occupational asthma caused by formaldehyde fumes, which was likely to be due to hypersensitivity, with late asthmatic reactions following formaldehyde exposure. Six workers developed immediate asthmatic reactions, which were likely to be due to a direct irritant effect as the reactions were shorter in duration than those seen after soluble allergen exposure and were closely related to histamine reactivity. The breathing zone concentrations of formaldehyde required to elicit these irritant reactions (mean 4.8 mg/m3) were higher than those encountered in buildings recently insulated with urea formaldehyde foam, but within levels sometimes found in industry. PMID- 4023976 TI - Airway responsiveness to histamine in man: effect of atropine on in vivo and in vitro comparison. AB - Airway responsiveness to histamine in man may be determined by the smooth muscle sensitivity to histamine or to the interaction between vagal nerve input and smooth muscle sensitivity. We have compared in vivo responsiveness to histamine with in vitro smooth muscle sensitivity to histamine in 20 non-asthmatic patients and one asthmatic patient undergoing thoracic surgery. Histamine responsiveness was assessed in the first 10 non-asthmatics without atropine pretreatment, in the second 10 after atropine pretreatment, and in the asthmatic patient both with and without atropine. In vivo responsiveness was also measured in 10 normal subjects and 10 asthmatic patients not undergoing surgery. Results were expressed as the provocation concentration (PC) causing a decrease in FEV1 of 20% (PC20FEV1) and in specific airways conductance of 35% (PC35SGaw), and in terms of maximal expiratory flow at 35% vital capacity, measured from the partial (V35(P] and complete (V35(C] flow volume curves of 35% (PC35V35(P); PC35V35(C]. In vitro smooth muscle sensitivity to histamine of bronchial tissue obtained at thoracotomy was expressed as the concentration causing a 50% maximum contraction (EC50) and as the maximum tension generated. There was considerable variation between patients in the in vivo responsiveness but a relatively narrow range for in vitro responses. There was no significant correlation between in vivo responsiveness, either with or without atropine pretreatment, and in vitro results. The asthmatic patient showed hyperresponsiveness in vivo but but not in vitro. These results suggest that in vitro airway smooth muscle sensitivity to histamine is not the sole determinant of in vivo airway responsiveness and that this lack of relationship is not explained by the influence of vagal nerve input on in vivo measurements. The results in the asthmatic patient suggest that airway hyperresponsiveness may be an in vivo phenomenon which is not related to a primary abnormality of airway smooth muscle. PMID- 4023978 TI - Incidence of sarcoidosis in the Isle of Man. AB - The incidence of sarcoidosis in a clearly defined island community has been determined in a seven year study. Special efforts were made to identify all cases, including those presenting to their general practitioners with only minor symptoms. A mean incidence of 14.7 per 100 000 per annum has been found in the years 1977-83 compared with an annual incidence of 3.5 per 100 000 in the preceding 15 years, when no specific attempts were made to identify sufferers from sarcoidosis. The lower figure is similar to the reported incidence in the United Kingdom and the difference is considered to be due to increased detection of cases during the study period. These findings suggest that a large proportion of cases of sarcoidosis in a general population may not be recorded in a registration system. PMID- 4023977 TI - Role of airway receptors in the breathing pattern of patients with chronic obstructive lung disease. AB - To determine whether airway receptors are responsible for the rapid, shallow breathing pattern seen in hypercapnic chronic obstructive lung disease, 10 patients underwent upper airway anaesthesia with inhaled lignocaine in a placebo controlled study. There was a significant reduction in breathing frequency after lignocaine (p less than 0.001) that was due to an increase in expiratory time (p less than 0.001). The inspiratory time remained unchanged, but tidal volume increased significantly (p less than 0.02). It is concluded that, while airway receptors may have a role in determining the frequency of breathing in chronic obstructive lung disease, other factors are responsible for the reduced inspiratory time. PMID- 4023979 TI - Effect of aminophylline on the human diaphragm. AB - The effect of intravenous aminophylline on the contractile function of the diaphragm was studied in four normal subjects. The contractility of the diaphragm was assessed by the measurement of transdiaphragmatic pressure (Pdi) after right phrenic nerve stimulation at 1 Hz. Pdi was measured before and during aminophylline infusion (6 mg/kg over 30 minutes), during which therapeutic concentrations of theophylline were attained (mean 13.8 mg/l, range 8.5-20.2). The Pdi achieved was not affected by aminophylline. This result suggests that theophylline at therapeutic concentrations has little effect on the contractility of the normal human diaphragm. PMID- 4023981 TI - Leiomyomas of the lower respiratory tract. AB - Leiomyomas account for about 2% of benign tumours of the lower respiratory tract. From the relatively few cases reported in the literature, it appears that these tumours most commonly occur in the fourth decade, although one third of patients are under the age of 20 years. The distribution of leiomyomas favours the distal part of the tracheobronchial tree and the most common site for tracheal lesions is the membranous portion of the lower third. Over 90% of pulmonary parenchymal leiomyomas, which themselves are more common in women, are incidental findings on chest radiographs whereas bronchial lesions are important causes of irreversible lung damage. Tracheal lesions may present as bronchial asthma. Accurate early diagnosis rests on a high index of clinical suspicion and histological examination of bronchoscopic biopsy specimens or frozen section material obtained at exploratory thoracotomy. Treatment could be conservative surgery, but 65% of reported cases have been managed by lobectomy or pneumonectomy as a result of advanced irreversible lung disease or unawareness of the benign nature of the lesion. PMID- 4023980 TI - Abnormalities of the lungs and thoracic cage in the Ehlers-Danlos syndrome. AB - Twenty patients with the Ehlers-Danlos syndrome, (10 type I, six type II, and four type IV) were studied to assess the frequency of respiratory abnormalities in this condition. Five patients (25%) had had at least one episode of haemoptysis, but none had any defect of coagulation. There was a high frequency of recurrent sinusitis, notably in those with the type I syndrome. Two patients had bullous lung disease, one of whom (type IV) had had three pneumothoraces and subsequent pleurodesis; he also had tracheomegaly (the Mounier-Kuhn abnormality). Minor skeletal abnormalities such as pectus excavatum were common, particularly in patients with type IV disease. Three patients had the straight back syndrome. There were no consistent spirometric or lung volume abnormalities, but eight patients (40%) had a raised gas transfer coefficient (Kco), possibly due to an increased intrapulmonary vascular volume. Two other patients had very low values of Kco that were unexplained. PMID- 4023982 TI - Radiographic changes in humidifier fever. PMID- 4023983 TI - Severe steroid responsive pneumonitis associated with pyoderma gangrenosum and ulcerative colitis. PMID- 4023984 TI - Multiple microscopic pulmonary arteriovenous connections in the lungs presenting as cyanosis. PMID- 4023985 TI - Pulmonary function in aluminium smelters. PMID- 4023986 TI - Occupational asthma due to heated freon. PMID- 4023987 TI - Plombage in the 1980s. PMID- 4023988 TI - Laser therapy in 100 tracheobronchial tumours. AB - One hundred patients with tracheobronchial tumours were treated with the neodymium YAG (yttrium-aluminium-garnet) or argon laser for symptoms of airways obstruction caused by tumour (59 cases), complete collapse of a lung (17 cases), or recurrent haemoptysis (24 cases). Seventy four of them had relapsed or failed to respond to radiotherapy or chemotherapy and all were inoperable. Objective improvement in results of lung function tests or haemoptysis diary charts was seen in 37 patients with airways obstruction (63%), five (29%) with collapsed lung, and 14 (58%) with haemoptysis. Overall, 68 patients had symptomatic benefit and there was objective improvement in 56. Two deaths occurred in 288 treatment sessions both occurring as a result of asphyxia from minor haemorrhage in patients with advanced cylindromas and critical narrowing of the trachea or single remaining bronchus. In suitable patients with intraluminal tumour laser phototherapy is a valuable addition to conventional treatment. PMID- 4023989 TI - A simple, inexpensive urine test of smoking. AB - Three novel colorimetric methods of detecting urinary nicotine metabolites called the barbituric acid, diethylthiobarbituric acid (DETB), and DETB extraction methods were evaluated for use as a simple, cheap, objective test of smoking. Urine samples were collected from 103 male smokers and 78 male non-smokers working at two London factories. The smokers recorded the number of cigarettes smoked over the previous 36 hours. All three methods correctly classified the smokers. The DETB extraction method had a lower false positive rate (averaging 3% on morning and afternoon urine samples) than either the DETB or the barbituric acid method (12% and 6% respectively) and was the best procedure for classifying subjects as "smokers" or "non-smokers." When a quantitative variant of the barbituric acid method was used there was a significant correlation (r = 0.85, p less than 0.001) between the ratios of urinary nicotine metabolites to creatinine and the number of cigarettes smoked. The ratios for smokers of 6-15, 16-25, and 26 or more cigarettes, however, overlapped considerably. The methods can be performed very rapidly and the reagent cost is equivalent to less than 1p per test. PMID- 4023990 TI - Changes in ventilation and its components in normal subjects during sleep. AB - Non-invasive measurements were made of ventilation, its derivatives, the contributions of abdomen and rib cage and arterial oxygen saturation in six healthy normal men whilst awake and during sleep. Minute ventilation fell significantly during slow wave (SW) sleep and rapid eye movement (REM) sleep (awake = 6.3 1 min-1, SW sleep = 5.7 1 min-1, REM sleep = 5.4 1 min-1; p less than 0.04). Mean inspiratory flow also fell significantly but timing was unchanged. The abdominal (diaphragmatic) contribution to ventilation fell very significantly during SW sleep but returned to awake levels during REM sleep (awake 54%, SW sleep 38%, REM sleep 56%; p less than 0.007). There were also significant falls in arterial oxygen saturation during SW and REM sleep (awake 97.3%, SW sleep 96.5%, REM sleep 96.2%; p less than 0.002). These falls represent reductions in arterial oxygen tension similar to those seen in patients with chronic airways obstruction and can be accounted for entirely by the associated reduction in ventilation. PMID- 4023991 TI - Thoracoscopic, histological, and clinical findings in nine case of rheumatoid pleural effusion. AB - A characteristic thoracoscopic picture of a granular parietal pleural surface was found in nine patients with rheumatoid pleurisy. Characteristic changes could be identified histopathologically in material obtained by biopsy. The rheumatoid pleural effusion resolved within an average of 14 months and no serious complications developed after the pleurisy. It is concluded that in rheumatoid pleural effusion a positive diagnosis can be made by thoracoscopy, preferably supported by the identification of microscopic structural changes in the parietal pleura. PMID- 4023992 TI - Bronchiectasis and oligospermia: two families. AB - Five patients from two families had a bronchiectasis syndrome; the men also had oligospermia with poor progressive sperm motility. None of the patients had cystic fibrosis, alpha 1 antitrypsin deficiency, immunoglobulin deficiency, structural abnormalities of the bronchi, or abnormalities of ciliary ultrastructure. Onset of pulmonary symptoms was in the neonatal period or infancy, and bronchitis and bronchiectasis were most severe in the middle and lower lobes. Two patients had sinusitis and two otitis. The two men old enough to be studied had 2-10 X 10(6) sperm/ml of ejaculate with less than 10% progressively motile. There were no other associated anomalies. These patients probably had a distinct genetic error predisposing to pulmonary infection leading to bronchiectasis and, in men, oligospermia with poor progressive motility. PMID- 4023993 TI - Mechanical ventilation for acute postoperative respiratory failure after surgery for bronchial carcinoma. AB - From 1978 to 1982 365 patients were treated surgically for bronchial carcinoma. Lobectomy was performed in 250 and pneumonectomy in 115. Sixteen (4.4%) needed mechanical ventilation for acute respiratory failure. Six out of eight with a lobectomy, but only two out of eight with a pneumonectomy, survived initially. Of these eight survivors, five died from recurrent malignancy within a year but three were alive and well at two years. The complications leading to acute respiratory failure were unpredictable in most patients. Improving techniques of mechanical ventilation and intensive care may lead to better results in the future. PMID- 4023994 TI - A study of swallowing difficulties in first degree relatives of patients with achalasia. AB - Of 167 patients with achalasia asked to provide details of swallowing difficulties among their first degree relatives, 159 completed the survey (95% response rate). One thousand and twelve first degree relatives were identified, and 14 were reported to have dysphagia including two with reported achalasia. Review of the case notes of these 14 relatives showed, however, that in none was achalasia confirmed. Heartburn affected 54 (5%) of the relatives, an incidence similar to that in the general population. These findings suggest that adult achalasia is not inherited in an autosomal recessive manner and that environmental factors during early life do not play an important aetiological part. PMID- 4023995 TI - Late complication of plombage thoracoplasty. PMID- 4023996 TI - Bronchocentric granulomatosis associated with seropositive polyarthritis. PMID- 4023997 TI - Extrathoracic lymph node aspiration in bronchial carcinoma. PMID- 4023998 TI - Nifedipine enhances the bronchodilator effect of salbutamol. PMID- 4023999 TI - Early lung development. PMID- 4024000 TI - Pulmonary platelet kinetics in asthma. AB - Platelets produce a range of bronchoconstrictor mediators. Measurements of plasma factors have implicated platelet activation in allergic asthma, and sensitised guinea pigs challenged with ovalbumin show pulmonary platelet aggregation accompanying bronchoconstriction. To investigate this further we injected autologous platelets labelled with indium 111 and red cells labelled with technetium 99m into three young volunteers with atopic asthma and three non asthmatic volunteers and, after equilibration of platelets between blood and splenic pool, monitored lung 99mTc and 111In activities continuously. Comparison with the corresponding activities in blood samples allowed calculation of pulmonary platelet to red cell transit time ratio (tp/tr). This ratio was 0.9, 1.02, and 0.98 in the non-asthmatic subjects compared with 1.04, 0.97, and 1.17 in the asthmatic subjects. This argues against the existence of an intrapulmonary platelet pool in normal subjects; transpulmonary transit time was slightly prolonged in one asthmatic subject. Bronchial challenge with Dermatophagoides pteronyssinus was performed in the asthmatic subjects and monitoring continued for a further 30 minutes. Antigen induced falls in FEV1 of 20-50% were accompanied by small decreases in the 111In but not in the 99mTc lung signal. In line with this tp/tr fell to 0.89, 0.89, and 1.05. Antigen induced bronchoconstriction was therefore not accompanied by intrapulmonary platelet accumulation. Platelet survival was normal at 10.2 days in both groups of subjects. PMID- 4024001 TI - Absence of refractoriness in asthmatic subjects after exercise with warm, humid inspirate. AB - Twelve asthmatic adults each completed two six minute treadmill runs separated by an interval of 20 minutes. Running speed was constant for each subject, and inspired air temperature averaged 5.5 degrees C (SD 1.5 degree) for both tests. Total minute ventilation and total respiratory heat loss showed no significant difference between the two runs. Forced expiratory volume in one second (FEV1) was measured before exercise and at five minute intervals throughout the recovery periods, during which subjects breathed room air at an average temperature of 17.8 degrees C (1.8 degree). Reduction in FEV1 from pre-exercise readings averaged 39.3% (13.3%) for the first run and 11.5% (7.3%) for the second. On another day the subjects underwent an identical procedure except that the first exercise period was performed with the saturated inspirate at 37.3 degrees C (1.7 degree). This run produced a mean FEV1 reduction of only 3.1% (7.3%). The ensuing run, during which the inspiratory temperature averaged 6.0 degrees C (2.0 degrees), led to a mean fall in FEV1 of 37.3% (17.3%). This was not significantly different from the value recorded for the first of the paired runs with cool air. We therefore have been unable to confirm that exercise with warm humid inspirate may induce refractoriness to exercise induced asthma. Our data are compatible with the theory that refractoriness may be due to depletion of mediators during an initial exercise induced asthma attack. PMID- 4024002 TI - Increase in mucociliary clearance in normal man induced by oral high frequency oscillation. AB - Data on the effect on mucociliary clearance of oral high frequency oscillation is conflicting. By means of a technique to superimpose high frequency oscillation on tidal breathing, changes in mucociliary clearance during high frequency oscillation were studied in seven normal non-smokers by monitoring the clearance of inhaled radiolabelled aerosol from the lungs. After inhalation of 5 microns technetium 99m labelled particles under controlled conditions, whole lung clearance was monitored by scintillation counters half hourly for six hours with a final count at 24 hours, from which tracheobronchial deposition and clearance could be calculated. Control and high frequency oscillation studies were performed on separate days in random order. Oral high frequency oscillation was applied by a bass loudspeaker through a mouthpiece to superimpose sinewave oscillations (RMS input pressure 1.2 cm H2O, mean pressure zero) on normal breaths. On high frequency oscillation days 30 minutes of oscillation alternated with 30 min of rest. Between 3 and 4.5 hours mucociliary clearance with high frequency oscillation exceeded control by about 10% (p less than 0.05). The mean time taken to eliminate 90% of deposited radioaerosol from the tracheobronchial tree fell from 4 hours 50 minutes (range 1 h 52 min-6 h 50 min) during control to 3 hours 43 minutes (range 2 hr 28 min-5 hr 54 min) during the high frequency oscillation run (p less than 0.05). Possibly this comfortable, simple technique would be of therapeutic benefit to patients with chronic sputum retention and merits further investigation. PMID- 4024003 TI - Study of lung function data by principal components analysis. AB - As a rational approach to the many lung function tests available, we have subjected the results of a battery of six lung function measurements made in 458 coalminers to the statistical technique of principal components analysis. By this means the six test results were reduced to three principal components without important loss of information. The first component appeared to represent lung size and the second the degree of airflow obstruction, and the third detected impairment of gas transfer factor in excess of that explained by the first two components. The values of the first principal component, used to select men with abnormal lung function, identified more younger men with functional abnormalities than a method based on comparison of observed and predicted values of forced expiration volume in one second. The values of the second and third principal components were used to classify types of functional abnormality. It is concluded that this statistical technique provides a sensitive method of identifying men with unusual lung function, particularly younger men, in a population and can be used to define and quantify different aspects of lung function. PMID- 4024004 TI - Incidence and aetiology of a raised hemidiaphragm after cardiopulmonary bypass. AB - A raised hemidiaphragm has been reported as an uncommon complication of cardiopulmonary bypass, possibly resulting from cold injury to the phrenic nerve. At Papworth Hospital myocardial protection during cardiac arrest relies in part on irrigation of the pericardial cavity with large volumes of Hartmann's solution at 4 degrees C. Retrospective review of the chest radiographs of 100 consecutive patients undergoing cardiopulmonary bypass showed that 31 had a raised left hemidiaphragm soon after operation. The only significant correlation was with aortic cross clamp time (p less than 0.03). A prospective study of 36 consecutive patients undergoing cardiopulmonary bypass was then undertaken with diaphragmatic screening and chest radiography. Preoperative screening gave normal results in all patients. In the early postoperative period 16 (44%) had left diaphragmatic weakness or paralysis, two (5.5%) right sided weakness, and two (5.5%) bilateral weakness. Repeat screening of these patients showed resolution in all but four cases (80%) at six months and in all but two (90%) at one year. The greater number of left sided lesions than of right (8:1) is probably due to the fact that the cold jet of irrigating fluid is directed towards the left phrenic nerve. These findings have implications with regard to the optimum temperature of the irrigant fluid for myocardial protection during cardiopulmonary bypass. PMID- 4024005 TI - Long term results of operation for shrinking pleuritis with atelectasis. AB - During 14 years 34 patients were operated on for shrinking pleuritis with atelectasis. They were followed up after one to 14 years (mean 6.0) by interview, chest radiography, and spirometry. Most were in good condition, but a reduction in vital capacity had occurred in eight and in FEV1 in 15 patients. Radiographs were normal in 28 patients except for small pleural or parenchymal fibrotic changes. One patient had a suspected recurrence of shrinking pleuritis with atelectasis after nine years, suggesting continuation of the disease process despite operation. PMID- 4024006 TI - Albendazole treatment of pulmonary hydatid cysts in naturally infected sheep: a study with relevance to the treatment of hydatid cysts in man. AB - Albendazole was given orally to sheep with naturally occurring live pulmonary and hepatic cysts. The viability of pulmonary cysts was established before treatment by thoracotomy and needle puncture. Both 10 and 20 mg/kg/day doses were found effective in that no viable protoscoleces were found after six weeks' treatment in either group while untreated controls still had viable cysts. In addition, treated animals showed macroscopic and electron microscopic changes. Bone marrow toxicity probably occurred in two sheep. PMID- 4024007 TI - A self paced treadmill walking test for breathless patients. AB - A treadmill exercise test is described that retains the advantages of self paced walking but allows the measurement of cardiorespiratory variables. A horizontal treadmill was modified to allow patients to control their own speed. During exercise continuous measurements of speed, distance, heart rate, arterial oxygen saturation, and stride length were made and subjective assessments of breathlessness were recorded on a visual analogue scale. Ten men with severe chronic obstructive lung disease performed a 12 minute corridor walk and a self paced 12 minute treadmill walk on the same day and repeat treadmill walks on different days. Six of them performed three walks or more. Six patients had ventilatory measurements during treadmill exercise. There was no significant difference (p greater than 0.1) in the distance covered during corridor and treadmill walks, and distances on the treadmill were repeatable after the first walk. Use of a mouthpiece significantly reduced the distance covered on the treadmill. The self paced treadmill walk is a simple repeatable test and has advantages over both a corridor walking test and standard progressive tests for assessment of breathless patients. PMID- 4024008 TI - Spirometric lung function tests in normal non-smoking Ethiopian men and women. AB - Forced vital capacity (FVC), FEV1, FEV1/FVC ratio (FEV1%), forced expiratory flow (FEF 200-1200), and peak expiratory flow rate (PEFR) were measured in 143 male and 117 female healthy Ethiopians. Multiple linear regression analysis was used to correlate these indices with anthropometric variables. The results show that FVC, FEV1, and PEFR give significant regressions with age and height in both sexes. These indices have significant regression coefficients with percentage body fat, weight, and fat free mass (FFM) expressed independently of height in the men; only PEFR is significantly regressed on weight and FFM in the women. FVC and FEV1 in Ethiopians are found to be lower than in caucasians and higher than in other Africans, Chinese, and Indians. Prediction equations are provided for future use for obtaining reference values for lung function indices in similar subjects. PMID- 4024009 TI - Intrapulmonary thymoma: report of two cases. PMID- 4024010 TI - Lymphangioleiomyomatosis presenting in a postmenopausal woman. PMID- 4024011 TI - Glucocorticoid hypersensitivity in an asthmatic patient: presentation and treatment. PMID- 4024012 TI - A substitute for "small airway disease"? PMID- 4024013 TI - Standardised lung function testing. PMID- 4024014 TI - [Simplified protocol for adjusting the dosage of theophylline]. PMID- 4024015 TI - [Comparison of the course of blood levels of bupivacaine and prilocaine after intra-articular irrigation administration for arthroscopy of the knee]. PMID- 4024016 TI - [Plethysmographic and pharmacokinetic study of a venotropic drug: disodium flavodate]. PMID- 4024017 TI - [Caudal anesthesia by lidocaine in children. Diffusion in the blood and possible cardiac effects]. PMID- 4024018 TI - [Value of gliclazide in the treatment of early diabetic retinopathy]. PMID- 4024019 TI - [Comparison of 2 different maintenance doses of caffeine in the treatment of apnea in premature infants]. PMID- 4024020 TI - [Inflammatory vasculitis and drugs]. PMID- 4024021 TI - [Guide for the imputability of drug-induced hepatitis]. PMID- 4024022 TI - [Hospitalization in hepatogastroenterology for iatrogenic pathology. Prospective study]. PMID- 4024023 TI - [Collaboration between the research center of a pharmaceutical firm and public emergency structures for better safety of phase I and II clinical pharmacology studies]. PMID- 4024024 TI - [Efficacy and observation of treatment within the framework of an association for home respiratory assistance]. PMID- 4024025 TI - [Plasma kinetics of digoxin in the presence of piretanide]. PMID- 4024026 TI - [Cutaneous necrosis after subcutaneous administration of gentamycin]. PMID- 4024027 TI - Dynamics of platelet tubulin in response to changes in free sulfhydryl groups. AB - Pools of polymerized and total tubulin were measured in human platelets as a function of free sulfhydryl groups both in acid-soluble and acid-precipitable cell fractions. Changes in free thiols were produced either by storage of platelets at room temperature or by addition of the potent oxidizing agent diazene dicarboxylic acid (diamide) and were correlated with shifts in the dynamic equilibrium between assembled and disassembled microtubules and platelet aggregation. Diamide at concentrations of 0.5 to 5 mM depleted acid soluble SH groups and reduced protein thiols while causing a progressive decrease in polymerized tubulin. Similar changes, although not as severe, were initiated by storage of platelets at room temperature. Platelet aggregation especially that induced by collagen showed a positive correlation with the pool of polymerized tubulin. Our results indicate that the state of oxidation of sulfhydryl groups especially in the acid-precipitable fraction plays an important role in determining the position of equilibrium between polymerized and depolymerized tubulin. PMID- 4024028 TI - The electrophoretic mobility heterogeneity of human platelet subpopulations of different buoyant densities. AB - Human platelets were separated into density subpopulations by using a step-wise gradient of Percoll in Tris-NaCl buffer. The absolute value of the electrophoretic mobility (EPM) of the density subpopulations was found to be a linear function of the density of the platelets, with EPM becoming less negative with increasing platelet density. Platelet volume distributions, mode volume, and sialic acid and protein contents were found to increase with platelet density, while no differences were found in GPII, GPIII, and GPIV contents among the subpopulations. An estimate of charge density was made from the ratio between the PAS-staining material (membrane GP's) and platelet surface area. The ratio was found to decrease as platelet density increased, consistent with the less negative EPM values observed for the higher density platelets. This lower surface charge of heavier platelets, which would lower charge repulsion between cells, agrees with the premise that heavier platelets are more active. PMID- 4024029 TI - A human pharmacological study comparing conventional heparin and a low molecular weight heparin fragment. AB - The pharmacokinetics of a heparin fragment of low molecular weight (LMWH) of 4000 5000 D and unfractioned standard heparin (UFH) have been studied after i.v. injections of different doses and infusions in 8 humans. The heparin activity was significantly higher and the effect on APTT lower after LMWH fragment as compared to UFH in the same doses. The half-life of heparin activity was about 1 hr for UFH and about 2 hr for LMWH. LMWH was found to be eliminated according to first order kinetics and there were no signs of dose dependency. PMID- 4024030 TI - Fibrinogen fragments X, Y, D and E increase levels of plasma fibrinogen and liver mRNAs coding for fibrinogen polypeptides in rats. AB - Previously, we demonstrated that in vivo regulation of liver fibrinogen synthesis occurs via the fibrinogen mRNA level. However, the molecular regulatory mechanism of fibrinogen synthesis is still not well understood. Fibrinogen or fibrin degradation products might play an important role in regulating fibrinogen synthesis. In our present study, we have injected rats intraperitoneally with purified homologous fragments and measured the liver content of mRNA specific coding for fibrinogen. Increased levels of fibrinogen mRNA and elevated plasma fibrinogen concentrations were observed in rats after administration of fibrinogen degradation products X, Y, DEGTA, Dcate or E. Fragment E or E' has a less stimulatory effect than X, Y or Dcate, whereas cross-linked fibrin degradation product D dimer does not increase fibrinogen synthesis. This article reports for the first time a stimulatory effect of the high molecular weight fibrinogen degradation products on fibrinogen synthesis. PMID- 4024031 TI - Methods in dose response platelet aggregometry. AB - A standardized method for performing dose response platelet aggregation has been developed, and has been used in about 1000 subjects in a large prospective study of ischaemic heart disease. A computer program has been used to fit a sigmoidal relationship between primary aggregation response rate and the log dose of aggregating reagent. Estimates of the parameters of the sigmoid curve are used to characterize an individual's platelet aggregability. Methods for investigating the maintenance of long-term quality control have also been developed. PMID- 4024032 TI - Sources of variability in dose response platelet aggregometry. AB - An experiment designed to assess the components of variability of a number of measures of platelet aggregability showed that the ADP ED50 (the estimated dose of adenosine diphosphate at which primary aggregation occurs at half its maximum velocity) had the least method error of any of the parameters measured, but that none had a very high between-person component of variability. A simultaneous comparison of a syringe technique and a free-flowing technique for venepuncture revealed no differential effects on the aggregation parameters measured. An enforced increase in the stirring speed in the aggregometer led to an experiment which showed that such a change did not apparently affect the ED50s. PMID- 4024033 TI - The effect of platelet number and haematocrit on whole blood thromboxane synthesis. AB - Whole blood, allowed to clot at 37 degrees C in glass tubes, synthesized thromboxane A2 (TxA2) as determined by radioimmunoassay for thromboxane B2 (TxB2). The time course for TxB2 synthesis showed no further increase after 60 min and the concentration of TxB2 in serum obtained from 60 normal subjects positively correlated with the whole blood platelet count in EDTA anticoagulated blood from the same donor. Patients with chronic renal failure produced less serum TxB2 than age- and sex-matched controls; they also had lower haematocrits. After re-calculating TxB2 production as a function of platelet count and haematocrit all but one of the patients fell in the range of values obtained for controls. These results suggest that chronic renal failure may not be associated with a cyclooxygenase defect and that clotted whole blood TxB2 production should be expressed as a function of platelet count and haematocrit. PMID- 4024034 TI - A role for pericellular proteoglycan in the binding of thrombin or antithrombin III by the blood vessel endothelium? The effects of proteoglycan-degrading enzymes and glycosaminoglycan-binding proteins on 125I-thrombin binding by the rabbit thoracic aorta in vitro. AB - Rabbit thoracic aorta segments were treated with either proteoglycan-degrading enzymes or with glycosaminoglycan-binding proteins to examine the nature of the endothelial and subendothelial binding sites of 125I-thrombin. Treatment (5-30 min) with enzymes (heparitinase, chondroitinases AC or ABC) caused a decrease in 125I-thrombin binding by the endothelium (30-70%) and by the subendothelial (intima-media) layer (20-50%); a low-specificity protease destroyed endothelial binding almost entirely and reduced binding to the subendothelium by approximately 60% over a similar period. Of the glycosaminoglycan-binding proteins, pretreatment of the aorta wall with protamine caused a 30% decrease in thrombin binding to the endothelium whereas lipoprotein lipase (present during 125I-thrombin uptake) decreased binding by up to 40%. Pretreatment with antithrombin III did not significantly affect binding of either 125I-thrombin or 125I-FPR-inactivated thrombin. In contrast to thrombin, 125I-antithrombin III was not readily uptaken by the aorta segments. These observations indicate that, whereas the minimal binding by 125I-antithrombin III probably does not involve endothelial proteoglycan, a strong case can be made for endothelial and subendothelial proteoglycan binding sites for thrombin. PMID- 4024035 TI - Urokinase quality: analysis of different preparations. AB - Five commercially available German Urokinase (UK) preparations were examined for purity, fibrinolytic activity, and molecular weight composition. With the exception of one preparation (B) all samples showed comparable fibrinolytic activity (91-107% of the activity declared). Preparations A, D, and E contained almost exclusively high-molecular-weight UK (HMW-UK), i.e., 82-86%. However, preparation C (from kidney tissue cultures) contained 95% of low-molecular-weight UK (LMW-UK), and sample B consisted of nearly equal amounts of both HMW-UK and LMW-UK (47:53). Purity criteria (coagulative and lysozyme activity, endotoxin content, protease activity, HBs antigen) were fulfilled by preparation E, and, with certain restrictions, also by preparations A and C. PMID- 4024036 TI - A functional plasminogen assay utilizing the potentiating effect of fibrinogen to correct for the overestimation of plasminogen in pathological plasma samples. AB - An overestimation of the plasminogen concentration occurs in patients with elevated levels of fibrin degradation products (fdp) and/or fibrinogen, when using assays based on the activation of plasminogen by streptokinase (Sk) followed by the hydrolysis of a synthetic chromogenic substrate. This source of error could be overcome by addition of fibrinogen in excess to the plasminogen assay thereby obtaining maximum stimulation of the Sk-plasminogen complex. The late degradation products of fibrinogen and fibrin, Dcate and Ddimer, respectively, had no potentiating effect on the Sk-plasminogen complex. The modified assay was designed as a manual method or for a centrifugal analyzer. The excellent reproducibility is illustrated by the coefficient of variation (CV) within series being 1.3% (n = 24) and from day to day being 1.9% (n = 20). PMID- 4024038 TI - Monitoring the intrinsic pathway of coagulation during heparin therapy--reply. PMID- 4024037 TI - Heparin assays and bleeding complications in treatment of deep venous thrombosis with particular reference to retroperitoneal bleeding. AB - Bleeding complications occurred in 30 (11%) out of 280 patients who received continuous heparin infusion for deep venous thrombosis (DVT). 22 (8%) had minor while 8 patients (3%) had major bleeding complications (1 intrathoracic [fatal], 2 gastrointestinal and 5 retroperitoneal). Heparin activity, in daily drawn blood samples, was determined by four assays (chromogenic substrate [CS] assay, activated partial thromboplastin time [APTT], thrombin time with citrated plasma [CiTT] and thrombin time with recalcified plasma [CaTT]). The differences in median heparin activity between patients with minor bleeding and patients with no bleeding did not reach significance for any of the tests. In patients with major bleeding, the differences were significant with the CS (p = .011) and the CaTT (p = .030) assays. Patients with retroperitoneal bleeding had significantly increased median activity judged by all four assays: CS (p = .002), CaTT (p = .003), APTT (p = .010), CiTT (p = .029). The difference was most pronounced after four days of heparin treatment, but there was a considerable overlap with patients without bleeding. PMID- 4024039 TI - Ether-phospholipid composition in neutrophils and platelets. AB - It is well documented that ether-lipids, especially the 1-0-alkyl-2-0-acyl-sn glycero-3-phosphocholine, can serve as precursors in paf-acether (platelet activating factor) biosynthesis. This study was undertaken to determine the amount of these compounds in two cell types which are good producers of paf acether: human neutrophils and rabbit platelets. The method of phospholipid analysis was based on selective destruction of diacyl molecules by lipase from guinea pig pancreas and of plasmalogens by acidolysis; phospholipids were then separated by bidimensional thin-layer chromatography. In platelets as in neutrophils, the major phospholipids were choline (37%) and ethanolamine (30 and 32%, respectively) phosphoglycerides and sphingomyelin (18 and 16%, respectively). In rabbit platelets the 1-alkyl molecules represented 15% of the choline class (0.7 nmol/10(7) cells). Neutrophils differed strikingly from platelets by the high level of these molecules which constituted 50% of the choline class (16.3 nmol/10(7) cells). It therefore appears that in the two cell types, the amount of 1-0-alkyl-2-0-acyl-sn-glycero-3-phosphocholine largely exceeded that would be necessary for paf-acether biosynthesis. PMID- 4024040 TI - Further studies on the role of red blood cells in spontaneous platelet aggregation. AB - The influence of red blood cells on platelet aggregation has recently been a subject of considerable interest. We have studied the effect of red cells on spontaneously formed platelet aggregates in rotating vials at 37 degrees C. Platelet aggregation was quantified by measuring the fall in number of single platelets with a whole blood platelet counter. Autologous packed red cells, platelet rich plasma and platelet free plasma were used to reconstitute aliquots of blood with constant platelet count but 0-60% haematocrit (Hct). The fall in platelet count was minimal at zero Hct, increased markedly with the Hct in the anaemic range and less markedly in the normal to polycythaemic ranges of Hct. Scanning electron microscopic observation of whole blood showed the presence of small platelet aggregates after about 3 mins rotation and very large aggregates after about 12 mins. ADP from red cells has been implicated in triggering platelet aggregation in whole blood. Whether aggregates are formed as a result of ADP leaking from the red cells or by their jostling physical action on the platelets is discussed. The marked effect of the red cells on spontaneous platelet aggregation however, justifies the manipulation of the Hct as a useful therapeutic option in the control of thrombotic and bleeding tendencies. PMID- 4024041 TI - The influence of a new low molecular weight sulphated polysaccharide from mussel broth (Org 30016) on haemostasis. AB - The effect on haemostasis of a new low molecular weight sulphated polysaccharide (4300 dalton) from mussel broth (Org 30016) was investigated. In an APT time test system it had an anticoagulant effect corresponding to 30-40% of that of heparin. It had no antithrombin effect. It exerted its effect only in test systems containing phospholipids. It did not prolong haemostatic plug formation time in the rabbit mesenteric microcirculation as did heparin. Formation of ex vivo Chandler thrombi was significantly inhibited. The practical interest of the substance comes from the combination of an antithrombotic effect and little influence on primary haemostasis. PMID- 4024042 TI - Red cell deformability and other haemorheological variables in stable coronary artery disease. AB - In this study, red cell deformability and other haemorheological variables were measured in 40 patients who underwent cardiac catheterization for the investigation of chest pain. The patients were divided into two groups - those with extensive disease and those with less extensive or no disease. Deformability was assessed by a filtration method. There were no significant differences in filterability, haematocrit, plasma viscosity or plasma fibrinogen between the two groups of patients. However, those with extensive disease had significantly higher blood viscosity than those with less extensive disease. Thus the study was able to demonstrate an association between blood viscosity and extent of coronary artery disease but not between the individual determinants of blood viscosity (red cell deformability, plasma fibrinogen and haematocrit) and extent of disease. PMID- 4024043 TI - Water-soluble urokinase derivatives of combined action. AB - Modification of urokinase by substances possessing useful therapeutic activity permits combined action preparations to be obtained. The catalytic properties of the modified enzyme are close to those of native urokinase. The attachment of sodium nitroprusside to it provides vasodilator action with a prolonged effect. Modification of urokinase by heparin produces stabilized preparations possessing fibrinolytic and anticoagulation activity simultaneously. The possibility of repeatedly modified urokinase obtaining has been demonstrated experimentally. Urokinase-heparin-sodium nitroprusside conjugates have fibrinolytic, hypotensive and anticoagulant effect simultaneously. The approaches suggested indicate possible new ways of creating effective therapeutics. PMID- 4024044 TI - Water-soluble urokinase derivatives with increased affinity to the fibrin clot. AB - The attachment of urokinase to fibrinogen via a "spacer" of aliphatic diamine increases the affinity of the modified enzyme to the fibrin clot. This provides increased (2.5-fold higher than for native urokinase) fibrinolytic activity of the modified urokinase. Modification of the enzyme does not affect its kinetic parameters, but increases its stability. It is shown that 1,12 dodecamethylenediamine is an optimal linking agent. Fibrinogen modified with diamines does not lose the ability to be co-polymerized in the three-dimensional fibrin clot under the action of thrombin and acquires increased stability towards proteolytic degradation. Use of fibrinogen as a carrier for thrombolytic drugs can increase their affinity to the injured site and enhance the local targeted action of therapeutic agent. PMID- 4024045 TI - Inhibition of platelet function with indobufen: correlation with plasma drug level. PMID- 4024046 TI - In vitro effect of cimetidine on platelet aggregation. PMID- 4024047 TI - The effect of heparin fragments of different molecular weights on experimental thrombosis and haemostasis. AB - The effect of heparin fragments of different molecular weights has been compared with that of conventional sodium heparin on experimental thrombosis in vivo and ex vivo and experimental haemostasis in vivo. In the first part of the study fragments of different molecular weights were given (4,900, 6,500, 9,500 and 22,200 dalton). All preparations including the control gave a significant prolongation of the haemostatic plug formation time in the rabbit mesenteric microcirculation, and all except the fragment with the lowest molecular weight reduced the frequency of jugular vein thrombosis (induced by a combination of endothelial denudation and stasis). There was a correlation between the XaI activity of the different heparin fragments and frequency of thrombosis. Using an ex vivo method (modification of Chandler's model) a dose dependent lag phase until start of thrombus formation was found. In the second part of the study a dose response investigation was made comparing different doses of a fragment (6,500 dalton) with conventional heparin in the same XaI doses (10, 30 and 60 units/kg). Sodium heparin in the highest dose prolonged the haemostatic plug formation time whereas none of the fragment doses did. The lowest dose both of the fragment and conventional heparin did not reduce the frequency of thrombosis, whereas the two higher doses did. Thus it may be possible to obtain preventive effect on thrombus formation with a heparin fragment. PMID- 4024048 TI - Human platelet reactivity with intact segments of rabbit aorta and selected regions of rabbit, rat and human aorta. AB - A technique measuring platelet reactivity with vessel wall subendothelium has been modified to examine platelet reactivity with vessel pieces in place of intact segments of aorta of a specific diameter. This modification of Baumgartner's original technique (1) allows measurement of blood platelet reactivity with vessel pieces, 5 X 10 mm in size, mounted on perfusion chambers with "twist bands." Adhesion and aggregation of human platelets to deendothelialized surfaces of intact segments of rabbit aorta and pieces of rabbit, rat and human aorta, were equivalent. This modification will expand the use of Baumgartner's technique to investigations of platelet vessel wall interactions using blood platelets and vessels from numerous experimental animal models and humans. It will also facilitate examination of possible differences in thrombogenocity of selected areas of vessels such as those exhibiting stages of atherosclerotic plaque formation. PMID- 4024049 TI - Studies of Wakan-Yakus (traditional herbal drugs): especially on the effects of Gaiyoh (Artemisiae folium) on blood coagulation. AB - Wakan-Yakus (traditional herbal drugs) such as Akyoh (Glutinum), Gaiyoh (Artemisiae folium), Sanshishi (Gardeniae fructus), Kizutsu (Aurantii fructus), and Taisoh (Zizyphi fructus) were studied in relation to their effects on blood coagulation-fibrinolysis. (1) All of the water extracts of the Wakan-Yakus prolonged aPTT and PT. The potency of the effectiveness on aPTT was in the order of Gaiyoh (Artemisiae folium) greater than Kizutsu (Aurantii fructus) greater than Sanshishi (Gardeniae fructus) greater than Taisoh (Zizyphi fructus) greater than Akyoh (Glutinum). (2) Gaiyoh (Artemisiae folium) greater than Kizutsu (Aurantii fructus) greater than Akyoh (Glutinum) greater than Taisoh (Zizyphi fructus) showed the antifibrinolytic effects in this order. On the other hand, Sanshishi showed the accelerating effect on fibrinolysis. (3) The inhibition modes of both thrombin and plasmin by Gaiyoh (Artemisiae folium) were shown to be competitive on Lineweaver-Burk plot. (4) Gaiyoh (Artemisiae folium) was gel filtered on Sephadex G-25 column (1.5 X 90cm) equilibrated with distilled water at room temperature. Five fractions were obtained, and in the first to fourth fraction, strong anticoagulant effects on aPTT and PT were observed. We pooled first and second to make fraction I, and make fraction II from peak 3. The recovery rate was 4.2% by weight, and 36.7% by inhibition activity, and specific activity on the basis of inhibition to aPTT was 34.8% U/mg in the case with fraction II. Fraction I was found to be the same characteristically on blood coagulation. Fraction II was further purified by Sephadex LH-20 column (1.5 X 80 cm) at room temperature. Three fractions (Fraction IIa, IIb, IIc) were obtained, and the strong inhibitory effects was observed on both aPTT and PT in each fraction. The first fraction (fraction IIa) showed the strong inhibitory effect on aPTT, and the heightened specific activity with 17.6% as the recovery rate. PMID- 4024050 TI - Interactions between sodium salicylate and acetyl salicylic acid evaluated using ADP induced platelet aggregation and bleeding time. AB - 1 g acetyl salicylic acid orally significantly enhanced the initial rate of platelet aggregation induced by 1 mumol/l and 2.5 mumol/l ADP. Sodium salicylate was without effects on the platelet aggregation and specifically it did not prevent acetylsalicylic acid from inhibiting the secondary aggregation. Sodium salicylate was without effect on the bleeding time and did not inhibit the prolongation induced by acetyl salicylic acid. Our study does not lend support to the concept of an important interaction in vivo between acetyl salicylic acid and its first metabolite salicylate in man. PMID- 4024051 TI - Metabolism of platelet activating factor (1-alkyl-2-acetyl-sn-glycero-3 phosphocholine) by capillary endothelial cells isolated from rat epididymal adipose tissue. PMID- 4024052 TI - Platelet attachment and spreading on polystyrene surfaces: dependence on fibronectin and plasma concentration. AB - Fibronectin promoted platelet attachment and spreading on polystyrene surfaces but was not essential if the surfaces were coated with plasma. The dependence of platelet adhesion on plasma concentration was complex. The extent of attachment and spreading was increased on surfaces treated with up to 1.0% plasma and decreased at higher plasma concentrations. The results support the hypothesis that protein adsorption is not directly related to protein concentration when surfaces are exposed to complex protein mixtures. PMID- 4024053 TI - Differences in platelet aggregation kinetics in normal and hyperlipidemic rabbits. AB - The difference in the aggregation mechanism between normal and hyperlipidemic rabbits was studied by kinetic analysis of changes in the number of residual single platelets in adenosine diphosphate (ADP)-induced platelet aggregation. When ADP was added to platelet rich plasma (PRP) obtained from normal rabbit, the number of single platelets decreased exponentially, but with PRP from hyperlipidemic rabbit, it decreased hyperbolically. However, the aggregation of platelets isolated from plasma of hyperlipidemic rabbit and resuspended in normal plasma showed an exponential decay, while that of normal rabbit platelets resuspended in hyperlipidemic rabbit plasma showed a hyperbolic decay. The results suggested that these aggregation mechanisms are altered mainly due to changes in the plasma components, such as the cholesterol levels. PMID- 4024054 TI - Fibrinopeptide A excretion in urine in patients with atherosclerotic artery disease. AB - Urinary fpA excretion and fpA in plasma were studied in patients with peripheral artery disease, aortic aneurysm, severe coronary artery disease, acute myocardial infarction and in normal controls. Mean urinary fpA was significantly higher in all groups of patients than in normal controls whose excretion was 1.9 +/- 1.2 micrograms/24 hours (mean +/- SD). We found a good correlation between urinary fpA excretion and plasma fpA (r = 0.68, p less than 0.01, n = 81). The highest levels of urinary fpA were found in 9 patients with aortic aneurysm (11.9 +/- 6.1 micrograms/24 hours). The 10 patients with acute myocardial infarction had also abnormally elevated values (4.3 +/- 1.8 micrograms/24 hours) which were only slightly higher than the levels found in another 10 patients with myocardial infarction receiving subcutaneous heparin in a dosage of 2 X 5000 IU daily (2.9 +/- 1.7 micrograms/24 hours). The 13 patients with peripheral artery disease showed an increase in urinary fpA excretion from 4.0 +/- 1.7 to 10.5 +/- 2.3 micrograms/24 hours after percutaneous angioplasty (p less than 0.001). These data demonstrate that urinary fpA excretion may represent a valid means to detect the cumulative effect of thrombin action on fibrinogen in patients with atherosclerotic vascular disease and after therapeutic intervention. PMID- 4024055 TI - Influence of human platelet factors on the proliferation of rat mesangial glomerular cells. PMID- 4024056 TI - [Prospective study of the presence of atrophic rhinitis and AR-pathogenic Bordetella bronchiseptica and Pasteurella multocida bacteria in piglets of health certified pig-breeding farms]. AB - Two hundred eight-week-old piglets from 20 pig-breeding farms, on which the clinical findings did not provide any justification for suspecting the presence of atrophic rhinitis (AR), were examined for this disease. Clinical parameters were brachygnathia superior (BS) and snout-distorsion (KD). Piglets with BS (n = 48) were observed on 13 farms and with KD on 8 farms. Morbid anatomical parameters were deviation of the nasal septum (SD) and atrophy of the ventral conchae (AVC). SD was observed in 76 piglets from 17 farms. Piglets with AVC gradation greater than or equal to 1 were recorded on 20 farms and with grade greater than or equal to 3 on 12 farms. The average gradation of AVC over all farms was 1.3 varying from 0.2 to 2.9. Bacteriological studies were done in the piglets for Bordetella bronchiseptica (BB) and AR pathogen Pasteurella multocida (PM+). The score of AVC showed a significant increase on farms on which infections with PM+ and BB was present. It is indicated that pig-herds with an average AVC gradation smaller than 0.7 do have a chance of less than 10% to be infected with PM+. BB was isolated from 52 piglets, from the nose in 49 cases and from the trachea in 27 cases respectively. PM was isolated from 67 piglets. Examination by equine blood agar showed that 15 piglets were positive for PM in the nose, 32 animals being found to be positive for PM by examination using mice. When mice were used in studies of the tonsils, 59 were found to be positive for PM. Of 45 piglets infected with type D, 16 were found te be PM+ following the guinea-pig skin test, the results being regarded as doubtful in two cases. Epidemiological studies for BB and PM+ on 117 breeding-farms in the Province of Overijssel showed that 92% of these farms were infected with BB and 28% with PM+. To be able to qualify breeding-farms as 'not being suspected of AR' concentrated clinical, pathological and bacteriological studies are required. PMID- 4024057 TI - [Food poisoning due to country sausage]. AB - Six children became seriously ill after eating dry sausages. The clinical symptoms and laboratory test suggested a case of poisoning by Staphylococcus aureus enterotoxin. The problems of enterotoxin analysis and the responsibility of the industry are discussed. PMID- 4024058 TI - [Polyarthritis in piglets caused by Mycoplasma hyorhinis]. PMID- 4024059 TI - [African swine fever: a threatening situation. Various comments on the current situation and the consequences for veterinary practice]. AB - Referring to recent outbreaks of African swine fever in Belgium, a number of practical aspects of this disease are reviewed. The fact that a vaccine is not available means that general and special health measures by the government and prevention should be emphasized. Moreover a number of logical conclusions as regards to veterinary practice are discussed. PMID- 4024060 TI - [From the Veterinary Chief Inspection of Public Health and the Board of the Veterinary Service. African swine fever in Belgium]. PMID- 4024061 TI - Analysis of chickens for recombination within the MHC (B-complex). AB - In an attempt to further map the chicken MHC (the B complex), a systematic search for genetic recombinants within the B complex was performed by serotyping the progeny from F2 crosses of chickens by means of specific anti-class I, anti-class II, and anti-class IV alloantisera. Two recombinant B-haplotypes (B21r and B15r) were found by analysing 2,656 F2 chickens representing 5,312 informative typings. In either case, the B-G (class IV) allele was recombined with both the B-F and B L alleles of the opposite haplotype. MLC typings, tests for direct compatibility by GVH reactions, and absorption analyses confirmed the original serological typing of the two recombinant B haplotypes. No recombination between B-F (class I) and B-L (class II) loci was found. This very low frequency of recombination within the B complex as compared with recombination frequencies found in mammalian MHC's is discussed. PMID- 4024062 TI - [Drainage--a possible treatment method in ascending umbilical abscess in calves]. PMID- 4024063 TI - [Diagnosis of an infestation with Collyriclum faba (Bremser, 1831) in a starling (Sturnus vulgaris L.) in Vienna]. AB - A massive infestation with Collyriclum faba (Bremser, 1831) was found in a young starling from Vienna. Always two trematodes formed cysts mainly in the subcutaneous tissues around the cloaca. In the presented starling there were additional cysts on the inner surface of the abdominal and thoracical wall, in the lung and on the rectum. PMID- 4024064 TI - [Electrocardiography in the horse (1). Principles and normal picture]. AB - The physiological and technical basis of the electrocardiography are shortly explained. The electrodes used for the recording of bipolare thoracal leads, their fixation on the horse, the practical procedure of a ECG-recording, its appearance and variation are described and illustrated. A recommendation for a systematic evaluation and interpretation is being proposed. PMID- 4024065 TI - [Functional anatomy of the visceral arteries in the abdominal cavity of the horse. Considerations with reference to intestinal colic]. AB - The microscopic structure of the arteries was investigated in the gastro intestinal tract of the horse. The median artery was also studied for comparative purposes. The adventitia is responsible for the holding and suspension of the visceral arteries. Disturbances in this system are considered to be a prime factor leading to chronically deficient blood flow. This is associated with pain which is generally classified as colics. PMID- 4024066 TI - [Results of the surgical treatment of colic, represented by case material of 1983 from the Munich-Riem horse hospital]. AB - The results of the ileus surgery in horses by a consistent performing of a known and standardised clinical and operative procedure are very good, provided that there are surgeons who have experience in abdominal surgery and that there is a co-operating team for the pre- and post-operative care. PMID- 4024067 TI - [Tomography in veterinary medicine. Possibilities for the application of this x ray technic demonstrated on the spinal column of a dog]. AB - After a short introduction of theoretical principles of tomography, the advantages of this technique--especially the representation of the dog's spinal column--are discussed with five case histories. This technique allows to produce isolated pictures of special parts of the spinal column which may be superpositioned by other body parts like: atlantooccipitalregion (especially dens axis), caudal cervical spine, thoracical spine and lumbosacral region. Particularly the evaluation of the intervertebral spaces, the small vertebral joints and the contours and structures of the vertebrae is enhanced, which is important in tumorous and infectious processes, as well as in fractures and luxations of the vertebrae. Besides the spatial association of certain structures is possible if their localization with conventional x-ray methods and even with exposures in two planes is unsuccessful. PMID- 4024068 TI - [Housing conditions and hygiene control in nutria breeding]. AB - Diseases in farm raised nutria (Myocastor coypus) often depend on hygienic fatalities in the different housing systems of the farms. The principle ways of accomodation for nutria are briefly described with reference to the specific hygienic problems. PMID- 4024069 TI - [Anglicisms in the German medical vocabulary]. AB - In view of an ever-increasing infiltration of the German medical vocabulary by Britishisms and Americanisms, a linguistic attempt was made to categorize this phraseology as follows: more or less incorporated terminology, "internationalized" terms, identical translations, unnecessary use of English expressions instead of German synonyms, borrowing from the English with an alteration of the original meaning, and German neologisms on the basis of English vocabular material. Specimens from all these categories are enumerated. PMID- 4024070 TI - Cardiovascular and respiratory effects of antiarrhythmic drugs on conscious beagles. AB - Cardiovascular effects of antiarrhythmic drugs and their effects on the respiratory rate were examined in conscious beagles. Disopyramide, 1.5 mg/kg i.v., increased the blood pressure and decreased the heart rate, but higher dose of 5 mg/kg i.v. increased both. Disopyramide showed no central nervous side effects. Procainamide, 20 and 60 mg/kg i.v., increased the blood pressure and heart rate without changing the respiratory rate. A higher dose (60 mg/kg i.v.) of procainamide induced vomiting. Lidocaine, 2 and 6 mg/kg i.v., and phenytoin, 3 and 10 mg/kg i.v., simultaneously increased the blood pressure, heart rate and respiratory rate accompanied by excitement, and with a higher dose (6 mg/kg i.v.) of lidocaine, by convulsions. Verapamil, 0.1 and 0.3 mg/kg i.v., induced tachycardia without serious neurological effects. In conscious healthy dogs cardiovascular depressant actions of antiarrhythmic drugs could only rarely be observed. PMID- 4024071 TI - Total cholesterol, high density lipoprotein cholesterol and choline esterase in overseas and Japanese university students. AB - Serum lipids were studied in 97 overseas and 282 Japanese university students. As compared with Japanese, serum total cholesterol levels were low and high density lipoprotein/total cholesterol ratio was high in the overseas students, especially in Chinese and Korean students. 30-39-year-old Chinese students, moreover, showed elevated high density lipoprotein levels. Choline esterase levels were significantly lower in 30-39-year-old Chinese and Korean students than in Japanese and Taiwanese. PMID- 4024072 TI - Calmodulin concentration in the uterus during pregnancy and influence of sex steroids. AB - Calmodulin concentration in pregnant rat uteri increased gradually and reached a level about three times that in non-pregnant rat at term. In human beings, uterine calmodulin content at term was about three times that in non-pregnant uteri, but there was no significant difference between the levels in uteri at term with and without labor pain. Estrogen increased the rat uterine calmodulin concentration, but progesterone did not change it. PMID- 4024073 TI - Precancerous lesions of the gallbladder mucosa. AB - To elucidate the morphological characteristics and the incidence of precancerous lesions of the gallbladder, 200 gallbladders removed for presumed benign diseases were examined histopathologically. Dysplastic epithelia with distinct cellular and structural atypia were graded into either mild or moderate to severe degree. Twenty-nine (14.5%) of 200 cases showed dysplasia; 5 (2.5%) was to moderate to severe degree and 24 (12%) to mild degree. Carcinoma in situ was found in 4 cases (2%) and occult invasive carcinoma in 2 cases (1%). Simple hyperplasia was seen in 54 cases (27%). Abnormal epithelia showed a male preponderance in consistent with the previous report on cancer epidemiology in Japan. Dysplasia and hyperplasia were found to have close association with chronic cholecystitis, but not with gallstones per se. It was postulated that the progression of dysplasia or carcinoma in situ into invasive carcinoma may occur in the sixties to seventies. PMID- 4024074 TI - Elevated cholecystokinin-like activity in the duodenal mucosa in patients with cholecystolithiasis. AB - Cholecystokinin (CCK)-like activities in the duodenal mucosa of the patients with cholecystolithiasis were determined with the bioassay method we established. The results obtained are as follows: The gall bladder of the patients with cholecystolithiasis following oral administration of egg yolk has contraction rates comparable to those of the normal subjects in the control group, whereas the contraction rate of the gall bladder of the patients with cholecystolithiasis following administration of caerulein was markedly lower than that of the normal subjects in the control group. The variations in the contraction of the gall bladder in time lapse following administration of caerulein to the patients with cholecystolithiasis strongly denied the possibility of either insufficient release of CCK or accelerated dissimilation of CCK in those patients. Based on the above findings, it was concluded that the sensitivity of the gall bladder to CCK decreases in the patients with cholecystolithiasis and that, in order to replenish it, the feed-back mechanism reacts to sufficiently promote the production of CCK in the duodenal mucosa. The similar mechanism was noted in the variations of the findings of normal subjects as age advanced. PMID- 4024075 TI - Constant growth of primary school children throughout four seasons of year. AB - Repeated measurements of body size (11 times for weight and 4 times for height during a 13 month period) in 1982-1983, and then in 1983-1984 disclosed that primary school children, both boys and girls in every year grade from 1st to 6th, grow in weight and height almost linearly throughout a year. Seasonal variation in growth pattern, once evident in around 1960, was no longer observed. Based on the observation, a formula to predict gains in weight and height is proposed and its value for the prevention of childhood obesity is discussed. PMID- 4024076 TI - Immunoprotective capability of somatic hybrid cells in comparison with parental tumor cells maintained in vitro. AB - The immunogenicity of X-irradiated hybrid cells derived from fusion of ASL-1 leukemia (A origin) and LM (TK-) fibroblasts (C3H origin) was compared to X irradiated parental ASL-1 leukemia cells maintained in vivo (V-ASL-1) and to X irradiated ASL-1 leukemia cells maintained in vitro (C-ASL-1). Immunization with hybrid cells induced transplantation resistance against tumor rechallenge with V ASL-1 more effectively than did immunization with V-ASL-1 tumor cells. Immunization with X-irradiated C-ASL-1 cells produced the same, or slightly stronger level of transplantation resistance than that with X-irradiated hybrid cells. These findings were observed both in A/J and in (C3H/HeJ X A/J)F1 mice. These results raise a question about whether the apparent increased immunogenicity of hybrid cells is due to a result of cell fusion or a result of their growth in vitro. PMID- 4024077 TI - Musculoelastosis: a change of small pulmonary arteries found in a case with atrial septal defect and pulmonary hypertension. AB - Interesting findings were obtained in the lung biopsy of a 46 year old female patient with secundum atrial septal defect and pulmonary hypertension. In the intima of small pulmonary arteries, there were a marked increase in elastic fibers and marked proliferation of longitudinal smooth muscle cells. The vascular lumen was markedly stenotic, but reconstruction of small pulmonary arteries indicated that all vascular lumina were patent. The case was accordingly diagnosed as operable and closure of atrial septal defect was undertaken. Three years postoperatively, the patient is well with much improved condition and lowered pulmonary arterial pressure was demonstrated by cardiac catheterization. This case had apparently serious vascular lesions due to severe intimal thickening which we labeled "musculoelastosis", but it was found that such thickening alone did not cause peripheral pulmonary arterial occlusion. It is therefore thought to be a benign pulmonary vascular condition. PMID- 4024078 TI - Unusual low affinity of human liver fibronectin for gelatin. AB - Fibronectin extracted from the human livers was shown to have very low affinity for gelatin unlike plasma fibronectin. It was demonstrated that this unusual property of liver fibronectin was not due to its proteolytic fragmentation. PMID- 4024079 TI - Motor time of the rectus femoris under loading of different weights. AB - Motor time (MT) of the rectus femoris was measured for seven normal subjects during rapid extension of the knee joint at 60 degrees flexion in the sitting position with and without external loads on the leg. MT prolonged linearly with external load from 0 to 4 kg. Tangent of this linearity, the rate of tension development (RTD), was significantly different from one another of the subjects and was not related to MT without external load. RTD is a relevant index to assess an efficiency of rapid force generation of a muscle. PMID- 4024080 TI - Late pulmonary response in guinea pigs after ascaris challenge. AB - Respiratory resistance of guinea pigs immunized with Ascaris suum was measured over 6 hr after aerosol challenge of the allergen by use of the oscillation method. These animals showed a biphasic pulmonary response to the aerosol challenge with Ascaris suum. Histological analysis of these animals revealed a narrowing of bronchial lumen, peribronchial edema and neutrophil-rich mucous in bronchial lumen at the late pulmonary response. PMID- 4024081 TI - Studies on the changes of serum bilirubin level after surgery in biliary atresia. AB - In biliary atresia, one-fourth of the patients showed prolonged jaundice in spite of a good excretion of bile after surgery. To investigate the cause of jaundice, factors related to the serum bilirubin level were examined in 28 recent cases. Furthermore, clinical analysis was performed in 86 cases of good excretion of bile after surgery. The following results were obtained: The daily amount of bilirubin excretion in bile and bilirubin concentration play an important role in decreasing the serum bilirubin level. The most important factor for prolonged jaundice is ascending cholangitis. Shortening of the life span of the red blood cells is one of the causes of prolonged jaundice. PMID- 4024082 TI - Comparison of cell profiles of bronchial and bronchoalveolar lavage fluids between normal subjects and patients with idiopathic pulmonary fibrosis. AB - The cell profiles of bronchial and bronchoalveolar lavage fluids (BLF and BALF) of patients with idiopathic pulmonary fibrosis (IPF) were compared with those of normal volunteers (NV) and age-matched control patients (CP), to characterize the cell profiles of the bronchoalveolar region in normals and patients with IPF. In BALF of nonsmokers from both control groups (NV and CP), alveolar macrophages (AM) were predominant and the percentage of neutrophil leukocytes and that of eosinophil leukocytes below 1% of the total cells. The percentage of neutrophils and that of bronchial epithelial cells were higher in BLF than in BALF of both control groups. Of the immune and inflammatory cells in BLF, the mean percentage of neutrophils was 12% in NV group and 42% in CP group. The percentage of neutrophils and that of eosinophils in BALF were higher in IPF group than in CP group, but the percentage of neutrophils in BLF of IPF group was comparable to that of CP group. In the IPF group, the percentage of neutrophils in BALF was lower than that in BLF. These results indicated that even in healthy subjects, a considerable number of neutrophils are present in the bronchial region and that the cell profile of the lavage fluid of the bronchoalveolar tree changes depending on the method of lavage. Presumably the higher percentage of neutrophils in BALF of patients with IPF is partly due to derangements of the alveolar structure, because the amount of saline infused into this region is limited. PMID- 4024083 TI - Diagnosis of adrenoleukodystrophy using dried blood spots. AB - We have demonstrated the increased C26:0/C22:0 ratio in the fatty acids of sphingolipid fraction in dried blood spots on filter paper from the patient with adrenoleukodystrophy. The ratio of C26:0/C22:0 in the dried blood spots from the patient was 2.1-fold higher than those of the normal controls. This value was almost the same as the ratio in erythrocyte membrane sphingomyelin from the patient, because sphingolipid fraction in the dried blood spots consists of mainly the sphingomyelin from erythrocyte membranes. Blood samples are easy to obtain by mail and the method is useful in the diagnosis of the patient and screening for the families known to be at risk. PMID- 4024084 TI - Particular cases of Cushing's syndrome--one with adrenocortical carcinoma and the other with double adenomas. AB - Two particular cases of adrenocortical tumors associated with Cushing's syndrome were documented. In the first case, the steroid pattern suggested a malignancy, and the histology of the excised tumor confirmed it. In the second case, the left adrenal had two distinct tumors; one dark-brown, and the other yellow in color. Recent trends in the diagnosis and treatment of Cushing's syndrome were discussed. PMID- 4024085 TI - Urinary glycosaminoglycans bearing glucuronic acid or iduronic acid residue at the reducing terminals. AB - The urinary glycosaminoglycan was reduced with NaB[3H]4, and was separated into three fractions according to molecular size by column chromatography on Sephadex G-200. The hexuronic acid residues at the reducing terminals of each fraction were quantified by the method of preferential quantitation of hexuronic acid at the reducing terminals. This method consisted of hydrolysis with trifluoroacetic acid and nitrous acid, lactonization, and paper chromatographic analysis. Both radioactive gulonolactone and idonolactone were detected in the fractions with a lower molecular size, but not in those with a higher molecular size. These observations demonstrated that the glucuronide and iduronide linkages at other than-terminal sites of carbohydrate chains were cleaved by the processes of depolymerization of glycosaminoglycans in tissues. Therefore, it is highly likely that endo-beta-glucuronidase(s) and endo-alpha-iduronidase(s) which belong to the glycosidase of endo type such as hyaluronidase are involved in the catabolic degradation of glycosaminoglycans in tissues. PMID- 4024086 TI - Nuclear changes in colo-rectal epithelium with special reference to nuclear inclusions in carcinoma, dysplasia, adenoma and Peutz-Jeghers polyps. AB - The incidence and types of unusual nuclear structures (UNS) were examined based on the observation of randomly photographed 1,919 nuclei in total from the normal epithelium, dysplasia, Peutz-Jeghers type polyp, adenoma and carcinoma of the large bowel. These nuclear structures were classified as filamentous, granular and vesicular inclusions, and invaginated structures were also taken into consideration. Although all types of UNS were found in the normal epithelium, carcinoma cells had the most numerous UNS, especially of the invaginated type. The possible process of nuclear inclusion (NI) formation was discussed in connection with malignant transformation of colo-rectal epithelial cells. PMID- 4024087 TI - Antitumor effect of the organogermanium compound Ge-132 on the Lewis lung carcinoma (3LL) in C57BL/6 (B6) mice. AB - Effects of the organogermanium compound Ge-132 (i.p.) were examined on the 3LL local tumor (1 X 10(5)/mouse, s.c.) and its pulmonary metastases in B6 mice. A characteristic feature of its action was the preferential antimetastatic effect under strictly defined conditions. Either inhibition or facilitation was observed depending on the treatment schedules; 7 daily doses of 100 mg/kg yielded the inhibition ratio 49% when started from day 1, whereas the treatment from day 8 resulted in the ratio -99%. The maximum inhibition was obtained at 100 mg/kg. The postsurgical-adjuvant treatment with Ge-132 was of no beneficial effect. The local tumor growth was affected only marginally and temporarily. When inoculum size was minimized (1 X 10(4)), a single dose of 300 mg/kg on day 1, but not on day 8, was effective in prolonging the latency before tumor take. The antitumor action of Ge-132 was discussed with reference to its interferon (IFN)-inducing activity. PMID- 4024088 TI - Studies on cholesterol esterase in cultured rabbit smooth muscle cells. AB - Acid and neutral cholesterol esterases (CEases) in cultured rabbit smooth muscle cells (SMC) were examined. The optimal pH of acid CEase was 4.5 and its apparent Km was 83 microM. The optimal pH of neutral CEase was 7.5 and its apparent Km was 38 microM. CEases were most active with substrate vesicles prepared with phosphatidylcholine. Acid CEase hydrolyzed cholesteryl [1-14C]oleate labeled LDL (LDL-CE), but neutral CEase did not. Incubation with LDL increased the acid and neutral CEase activities of SMC, but incubation with acetylated-LDL did not increase their activities. PMID- 4024089 TI - ApoE-2/E-3 ratio of very low density lipoprotein in diabetes mellitus. AB - Apolipoprotein E (apoE) of very low density lipoprotein (VLDL) in 22 diabetic patients was analysed by the method of one-dimensional isoelectrofocussing (IEF). We modified the IEF-method of Kashyap et al. by which apoE isoproteins were easily and accurately determined. The measurement of apoE-2/E-3 ratio was useful for determining apoE phenotypes. In 17 of 22 diabetics apoE phenotype was E3/3, while three patients showed E2/3 and two showed E3/4. ApoE-2/E-3 ratio was reduced from 0.91 +/- 0.07 to 0.73 +/- 0.04 (p less than 0.05) by the one month period treatment in 10 insulin required diabetics. The ratio was also reduced from 1.06 +/- 0.14 to 0.89 +/- 0.09 (p less than 0.2) in 10 non-insulin required diabetics. The reduction in apoE-2/E-3 ratio was caused by an increase in apoE-3 band and a decrease in apoE-2 band which might be attributed to the changes in the sialic acid-content of isoproteins on the one-dimensional IEF method. Therefore, apoE phenotypes in diabetic patients should be determined when their diabetic state is improved. PMID- 4024090 TI - Response properties of prefrontal visual neurons in the awake monkeys. AB - Response properties of the visual neurons in the prearcuate and periprincipal areas of the prefrontal cortex were examined in awake monkeys. The findings obtained are as follows: (1) Most of the visual neurons responded with various excitatory fashions to a light spot presented in their visual receptive fields (RFs). The response was large when the stimulus was applied to the middle of the RF and became smaller when the stimulus position was moved from this part toward the RF border. (2) The response was affected by the size of the stimulus. The largest response was usually obtained by a small stimulus. The shape, orientation, brightness of the stimulus and the direction of its movement gave little influence on the response strength and pattern. (3) In about a half of the neurons the response was enhanced when the monkey made a saccadic eye-movement toward a visual stimulus in the RF. (4) Some of the above-mentioned response properties were quantitatively different from one another among neuron groups classified according to the eccentricity and size of their RFs. These results suggest that the properties of the neurons are suitable for detecting a visual stimulus occupying a limited extent in the space. PMID- 4024091 TI - Increase in blood pressure in pheochromocytoma induced by domperidone and metoclopramide. AB - Administration of two dopamine antagonists, domperidone and metoclopramide, gave a marked rise in blood pressure with an increase in plasma catecholamines in two patients with pheochromocytoma. The result suggests that not only metoclopramide but also domperidone might induce hypertensive crisis in pheochromocytoma. PMID- 4024092 TI - Semiquantitation of ABH antigens specific for red blood cells. AB - H and A antigens expressed only in the RBC were quantitated using specific antisera, and the amount of the antigens was compared with that of total H and A antigens shared by the RBC and saliva. Total H antigen decreased in the order of O, A, B and AB blood groups. However, H antigen specific for the RBC distributed similarly among four blood groups. In addition, the amount of total A antigen in A group was more than that of AB group, but the difference in the amount of A antigen specific for the RBC was not significant between the two blood groups. B antigen specific for the RBC was not examined because of failure in preparing specific anti-B serum. In conclusion, the quantitative difference of the total H or A between A and AB groups might be due to the difference in the amount of antigen common to the RBC and saliva but not one specific for the RBC. PMID- 4024093 TI - Evidence for direct effect of growth hormone on capillary basement membrane thickness. AB - In order to investigate the direct effect of growth hormone on the capillary basement membrane thickness (CBMT), we performed, in normal and diabetic rats, ultrastructural morphometric studies on the capillaries of the skin loci where the intracutaneous injections of physiologic saline and human growth hormone (HGH) in various concentrations had been repeated daily for 28 days. In the normal group, the injection (0.1 ml daily) of HGH solutions in concentrations of 0.5 micrograms/ml and 2 micrograms/ml did not significantly alter the CBMT, and only at the concentration of 10 micrograms/ml, HGH significantly (p less than 0.001) increased the CBMT. In the diabetic group, however, the injection of any of the HGH solutions significantly (p less than 0.001 approximately 0.05) increased the CBMT. In another diabetic rat series, HGH, human albumin, human menopausal gonadotropin and human globulin (each in a concentration of 10 micrograms/ml) were repeatedly injected into four separate skin portions for 28 days, and it was found that the net increase in CBMT was most striking in the HGH treated portion. These data demonstrated the direct and specific effect of HGH on CBMT. PMID- 4024094 TI - A further study on the polymorphism of placental alkaline phosphatase in Japanese. AB - Polymorphism of placental alkaline phosphatase (PL) was investigated in 120 Japanese placentae by means of starch gel electrophoresis and an improved staining method for the isoenzymes using naphthol AS-MX phosphate as substrate instead of beta-naphthyl phosphate. The present method gave more satisfactory results for the detection of the PL bands. Besides five of the six common phenotypes three different uncommon variants were identified. The gene frequencies of PL types were estimated at PL1 = 0.729, PL2 = 0.054, PL3 = 0.200 and PLv = 0.017, which were very similar to those reported in other districts of Japan. PMID- 4024095 TI - Alternations of liver pathophysiology in experimental hepatic failure treated by two forms of plasma purification procedure. AB - Plasma cross-circulation which resembles plasma exchange and plasma perfusion over charcoal and resin adsorbents were carried out using rats with galactosamine (GalN)-induced hepatic failure to investigate the effects of those plasma purification procedures on damaged liver function. Twenty-four hr after the injection of GalN, the plasma treatment procedures were performed at a plasma flow rate of 0.1 ml/min for 6 hr. Forty-eight hr after the injection of GalN, ATP synthesis in liver mitochondrial function, and ATP and total adenine nucleotide contents in the liver, which were markedly reduced by the GalN administration, were increased by both plasma cross-circulation and plasma perfusion over adsorbents. These results suggest that both plasma purification procedures improve the deterioration of mitochondrial phosphorylation activity and produce an augmented high energy status in the liver. In the histological study of the liver, volume ratio of hepatic parenchyma in the GalN-treated liver to that in the normal liver was significantly higher in rats treated with plasma perfusion than those with sham-perfusion. An efficient removal of the hepatotoxic metabolites from the plasma, therefore, decelerates the progress of GalN induced liver tissue necrosis, if rats with GalN-induced hepatic failure are treated in an early stage. PMID- 4024096 TI - Exposure concentration versus environmental concentration: a field survey in organic solvent workplaces. AB - The relationship was investigated between the environmental concentrations in workplaces and the concentrations in the breath zones of the workers therein. The former was measured in 47 organic solvent workplaces of various types taking both the grid-sampling strategy (Measurement A) and a spot-air sampling to detect possible maximum exposure (Measurement B), while the latter was determined by the application of personal samplers to 328 workers. Although a low yet significant correlation was observed between the results of Measurement A (i.e., the combination of the geometric mean and the geometric standard deviation of the environmental concentration) and the exposure concentration, excess exposure (i.e., over occupational exposure limit exposure) would occur in some workplaces when the occupational exposure limit itself be used as the limit value for the setting of criterion for environmental concentration. The analyses of the experiences suggest no excess exposure would be expected if half the occupational exposure limit be employed as the limit value. PMID- 4024097 TI - Evaluation of sequential glucose metabolism in cerebral ischemia using a chrono autoradiographic method. AB - A chrono-autoradiographic technique (sequential double label 2-deoxyglucose method) was performed to evaluate postischemic regional glucose metabolism. Using this method, two sequential autoradiograms, one immediately after the stroke and one 7-8 hr after the stroke, were obtained from the same brain slice. Comparison of the two images strongly suggested that the ischemic core and the regions adjacent to the core died, while the periphery recovered from the metabolic injury, and that postischemic metabolic abnormality itself didn't necessarily determine the fate of the ischemic tissue. PMID- 4024098 TI - The automated analysis of coordinated hindlimb movement in rats during acute and prolonged exposure to toxic agents. AB - The effects of CNS-active drugs and neurotoxic agents on motor coordination in the rat were studied using a newly developed, automated technique. In this test, a tv/microprocessor-based system was utilized to detect and describe the movement and placement characteristics of one of the rat's hindpaws as the rat placed its paw from one rung to another while walking in a rotating wheel. In studies employing a wheel speed of 8.2 cm/sec and a single 90-sec trial, significant deficits in coordinated hindlimb movement could be detected following the acute ip administration of a variety of compounds, including acrylamide (0, 50, and 100 mg/kg), diazepam (0, 0.5, 1.0, and 2.0 mg/kg), ethyl alcohol (0, 600, 900, and 1200 mg/kg), and tremorine (0, 2.5, 5.0, and 10.0 mg/kg). Further, results from a subacute study involving the oral administration of 2,5-hexanedione (2,5-HD; 0, 250, and 600 mg/kg) indicated that rats treated with 600 mg/kg, 2,5-HD were significantly impaired after 1 week of treatment and those treated with 250 mg/kg 2,5-HD, after 2 weeks of treatment. Although both groups improved during the recovery period, the performance of the 600 mg/kg group 5 weeks post-treatment was still inferior to controls. Taken together, these studies indicate that the coordinated hindlimb placement test provides a reliable, sensitive, and rapid technique for quantifying deficits in motor coordination in the rat during acute and prolonged exposure to neurotoxic substances. PMID- 4024100 TI - The metabolism of di(2-ethylhexyl) phthalate (DEHP) and mono-(2-ethylhexyl) phthalate (MEHP) in rats: in vivo and in vitro dose and time dependency of metabolism. AB - This study investigated the in vivo metabolism of di(2-ethylhexyl) phthalate (DEHP) and mono(2-ethylhexyl) phthalate (MEHP) in rats after multiple dosing, the metabolism of MEHP in primary rat hepatocyte cultures for periods of up to 3 days, and the biotransformation of some major metabolites of MEHP. Rats were orally administered [14C]DEHP or [14C]MEHP at doses of 50 and 500 mg/kg body wt for three consecutive days. Urine was collected at 24-hr intervals, and metabolite profiles were determined. After a single dose of either compound, urinary metabolite profiles were similar to those previously reported. However, after multiple administration of both DEHP and MEHP at 500 mg/kg, increases in omega-/beta-oxidation products [metabolites I and V, mono(3-carboxy-2 ethylpropyl) phthalate and mono(5-carboxy-2-ethylpentyl) phthalate, respectively] and decreases in omega - 1-oxidation products [metabolites VI and IX, mono(2 ethyl-5-oxohexyl) phthalate and mono(2-ethyl-5-hydroxyhexyl) phthalate, respectively] were seen. At the low dose of 50 mg/kg little or no alteration in urinary metabolite profiles was observed. At 500 mg/kg of MEHP a 4-fold stimulation of CN- -insensitive palmitoyl-CoA oxidation (a peroxisomal beta oxidation marker) was seen after three consecutive daily doses. At the low dose of 50 mg/kg only a 1.8-fold increase was noted. Similar observations were made with rat hepatocyte cultures. MEHP at concentrations of 50 and 500 microM was extensively metabolized in the rat hepatocyte cultures. Similar metabolic profiles to those seen after in vivo administration of MEHP were observed. At the high (500 microM) concentration of MEHP, changes in the relative proportions of omega- and omega- 1-oxidized metabolites were seen. Over the 3-day experimental period, omega-/beta-oxidation products increased in a time-dependent manner at the expense of omega - 1-oxidation products. At a concentration of 500 microM MEHP, a 12-fold increase of CN- -insensitive palmitoyl CoA oxidation (a peroxisomal beta-oxidation marker) was observed. At the low concentration of MEHP (50 microM) only a 3-fold increase in CN- -insensitive palmitoyl-CoA oxidation was noted and little alteration in the metabolite profile of MEHP was observed with time. Biotransformation studies of the metabolites of MEHP confirmed the postulated metabolic pathways. Metabolites I and VI appeared to be endpoints of metabolism, while metabolite V was converted to metabolite I, and metabolite IX to metabolite VI. It was also possible to reduce the transformation of metabolite X [mono(2-ethyl-6-hydroxyhexyl) phthalate] to metabolite V.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 4024101 TI - Effects of 3-methylcholanthrene and phenobarbital on the capacity of embryos to bioactivate teratogens during organogenesis. AB - Pregnant Sprague-Dawley rats were divided into four groups and given ip injections of 3-methylcholanthrene (MC) in corn oil, corn oil only, phenobarbital (PB) in Hank's balanced salt solution (HBSS), or HBSS only. Maternal animals were killed on Day 10 of gestation, and embryos from each group were explanted in medium containing cyclophosphamide (CP), 2-acetylaminofluorene (AAF), or dimethylsulfoxide vehicle. After a 24-hr culture period, embryos from dams treated with HBSS, corn oil, or PB/HBSS exhibited no increase in abnormalities (as compared with controls) when either CP or AAF were added to the media. However, embryos transplacentally preexposed to MC and subsequently treated during culturing with AAF (but not CP) exhibited striking increases in malformation incidence. Commonly observed malformations included abnormally open neural tubes, abnormal flexure rotation, and prosencephalic defects. Homogenates of Day 10 embryos transplacentally preexposed to MC exhibited readily measurable oxidative biotransformation of AAF as assessed with HPLC. Biotransformation of AAF by embryos from the other three groups was virtually undetectable. Incorporation of exogenously supplemented bioactivating systems from livers of mature animals indicated that postmitochondrial supernatant fractions (S-9) from male, MC-pretreated rats effectively catalyzed the conversion of AAF (but not CP) to embryotoxic metabolites. Conversely, hepatic S-9 from adult, male, PB pretreated rats was highly effective in converting CP (but not AAF) to embryotoxic metabolites. The results indicated the inducerspecific occurrence of embryonic bioconversion of AAF to embryotoxic metabolites via MC-inducible, P-450 dependent, embryonic enzyme systems. PMID- 4024099 TI - Developmental phase-specific and dose-related teratogenic effects of ethylene glycol monomethyl ether in CD-1 mice. AB - Several animal species have shown a teratogenic response to inhaled or ingested ethylene glycol monomethyl ether (EGME). The present study examined the developmental phase specificity and dose-response characteristics of EGME-induced embryotoxicity. Pregnant CD-1 mice (vaginal plug positive day = gestation Day [gd]0) received multiple or single doses of EGME by gavage between gd 7 and 14. Fetuses were examined on gd 18 for external and skeletal malformations. EGME was not maternally toxic after multiple doses of 250 mg/kg or a single administration of up to 500 mg/kg. EGME induced embryotoxicity as manifested by reduced gd 18 fetal weights and increased resorptions. The observed malformations were specifically related to the developmental stage at the time of exposure. Exencephaly resulted after EGME exposure between gd 7 to 10 whereas paw anomalies (syndactyly, oligodactyly, and stunted digit No. 1) predominated during later stages of development. Paw anomalies were maximal after administration on gd 11, and forepaws exhibited greater susceptibility than hindpaws. The no observed effect dose for the induction of digit malformations after a single administration of EGME on gd 11 was 100 mg/kg. At 175 mg EGME/kg digit anomalies were induced without any concurrent reduction in fetal body weight while at 250 mg/kg and above, digit anomalies occurred concurrently with reduced fetal body weight. PMID- 4024102 TI - Postnatal methyl mercury exposure: effects on ontogeny of renal and hepatic ornithine decarboxylase responses to trophic stimuli. AB - The effects of postnatal methyl mercury exposure on the ontogeny of renal and hepatic responsiveness to trophic stimuli were examined. Increased ornithine decarboxylase (ODC) activity was used as an index of tissue stimulation. In the rat, renal ODC responsiveness to growth hormone, angiotensin, vasopressin, isoproterenol, and serotonin was absent at birth and matured 3 to 4 weeks later. However, pups exposed to methyl mercury showed marked, ODC responses to these same agents as early as 10 to 19 days of postnatal age, accompanied by a significant renal hypertrophy. In contrast to the kidney, the liver of normally developing rats was responsive to trophic factors even in the neonate. In this tissue, there was no consistent effect of neonatal methyl mercury treatment on ODC responses at any developmental stage tested; although absolute liver weights were reduced, liver/body weight ratio was not affected. These results demonstrate that postnatal methyl mercury exposure causes a precocious onset of ODC responses to trophic agents specifically in the kidney. Altered responsiveness may mediate some of the effects of this organomercurial on overall renal development and function. PMID- 4024103 TI - The embryotoxicity of adriamycin in rat embryos in vitro. AB - Adriamycin (ADR) is a widely used and highly valued antineoplastic agent but chronic treatment is limited by cardiotoxicity. To investigate its embryotoxic potential, cultured rat embryos were exposed to ADR at concentrations ranging from 0.4 to 1.2 microM. Within this range, ADR elicited decreases in growth parameters (somite numbers, embryonic length, and protein and DNA content), malformations involving the prosencephalic region, and embryolethality at the higher concentrations. Embryotoxicity was significantly increased (p less than 0.05) when cultures included cofactors for cytochrome P-450-dependent biotransformation and a hepatic microsomal preparation (S-9) prepared from animals pretreated with 3-methylcholanthrene or a mixture of polychlorinated biphenyls (Aroclor 1254). When S-9 from control animals or from rats pretreated with phenobarbital was used, significant increases in ADR-elicited embryotoxicity were not observed. Substitution of NADH for NADPH as a cofactor reduced the incidence of malformations from 100 to 60% at ADR concentrations of 0.5 microM. Increasing O2 concentrations partially counteracted the embryotoxic effects of ADR. Several other agents [including various antioxidants, compounds bearing free sulfhydryl groups, coenzyme Q10, and superoxide dismutase (with or without catalase)] that prevent or reduce the cardiotoxicity of ADR without impairing its antineoplastic properties, failed to modify the embryotoxicity significantly. This suggested that the embryopathic and antineoplastic properties of ADR may share a common mechanism which is distinct from that responsible for cardiotoxicity. PMID- 4024104 TI - Identification and quantification of urinary metabolites of dinitrotoluenes in occupationally exposed humans. AB - Rats exposed to technical grade dinitrotoluene (DNT) develop hepatocellular carcinomas. Humans may be exposed to DNT during its manufacture and use. To permit comparisons of human excretion patterns of DNT metabolites with those previously observed in rats, urine specimens were collected over a 72-hr period from workers at a DNT manufacturing plant. Samples were analyzed for 2,4- and 2,6 DNT and putative metabolites by gas chromatography-mass spectrometry. Urine from workers exposed to DNT contained 2,4- and 2,6-DNT, 2,4- and 2,6-dinitrobenzoic acid, 2,4- and 2,6-dinitrobenzyl glucuronide, 2-amino-4-nitrobenzoic acid, and 2 (N-acetyl)amino-4-nitrobenzoic acid. Excretion of these metabolites peaked near the end of the workshift, but declined to either very low or undetectable concentrations by the start of work the following day. The calculated half-times for elimination of total DNT-related material detected in urine ranged from 1.0 to 2.7 hr, and those of individual metabolites from 0.8 to 4.5 hr. The most abundant metabolites were 2,4-dinitrobenzoic acid and 2-amino-4-nitrobenzoic acid, collectively accounting for 74 to 86% of the DNT metabolites detected. The data indicate that urinary metabolites of DNT in humans are qualitatively similar to those found in rats, but quantitative differences exist in the relative amounts of each metabolite excreted. PMID- 4024105 TI - Identification of the proximate peroxisome proliferator(s) derived from di(2 ethylhexyl) phthalate. AB - A primary rat hepatocyte culture system was utilized to determine the proximate peroxisome proliferator(s) derived from di(2-ethylhexyl) phthalate (DEHP). DEHP was administered to rats and the urinary metabolites were identified and isolated. The major metabolites were those resulting from initial omega- or omega - 1-carbon oxidation of the mono(2-ethylhexyl) phthalate (MEHP) moiety. These metabolites, together with MEHP and 2-ethylhexanol, were added to primary rat hepatocyte cultures and the effect on peroxisomal enzyme activity was determined. The omega-carbon oxidation products [mono(3-carboxy-2-ethylpropyl) phthalate (I) and mono(5-carboxy-2-ethylpentyl) phthalate (V)] and 2-ethylhexanol produced little or no effect on CN- -insensitive palmitoyl-CoA oxidation (a peroxisomal marker). MEHP and the omega - 1-carbon oxidation products [mono-(2-ethyl-5 oxohexyl) phthalate (VI) and mono(2-ethyl-5-hydroxyhexyl) phthalate (IX)] produced a large (7- to 11-fold) induction of peroxisomal enzyme activity. Similar structure-activity relationships were observed for the induction of cytochrome P-450-mediated lauric acid hydroxylase and increase in cellular coenzyme A content. This identification of the proximate proliferators will aid in the elucidation of the mechanism by which DEHP causes proliferation of peroxisomes in the rodent liver. Oral administration of MEHP (150 or 250 mg/kg) to male guinea pigs did not produce hepatic peroxisome proliferation. Addition of MEHP (0 to 0.5 mM) or one of the "active" proliferators in the rat (metabolite IX, 0 to 0.5 mM) to primary guinea pig hepatocyte cultures also failed to produce an induction of peroxisomal beta-oxidation. Possible reasons for this species difference are discussed. PMID- 4024106 TI - Effects of cadmium on glutathione peroxidase, superoxide dismutase, and lipid peroxidation in the rat heart: a possible mechanism of cadmium cardiotoxicity. AB - Cadmium treatment of rats maintained on a low-selenium diet produced a significant increase in specific heart weight together with histopathological changes. This increase was accompanied by a decrease in the activities of the selenoenzyme, glutathione peroxidase, and the copper-containing enzyme superoxide dismutase, together with a rise in thiobarbiturate-reactive substances in the heart. Increased dietary selenium prevented the lowering of glutathione peroxidase activity but did not influence the effect of cadmium on superoxide dismutase. The effect of cadmium on thiobarbiturate-reactive materials was markedly reduced in the rats fed high dietary selenium. PMID- 4024107 TI - Cellular responses to O,O,S-trimethyl phosphorothioate-induced pulmonary injury in rats. AB - O,O,S-Trimethyl phosphorothioate (OOS-TMP), an impurity of many organophosphorus insecticides, causes a delayed toxicity in rats and mice which is associated with morphological and biochemical changes in the lung. Oral administration of doses as low as 20 mg/kg alters bronchiolar epithelial morphology and causes an increase in bronchopulmonary lavage lactate dehydrogenase levels. In the present study, the effects of OOS-TMP on alveolar and bronchiolar cells were examined by determining the patterns of cellular regeneration in rats at periods of 12 hr, 24 hr, 3 days, and 7 days after treatment. Dividing cells were labeled with tritiated thymidine and studied with autoradiographic techniques. The results showed that OOS-TMP treatment initiated proliferation of alveolar type II cells within 24 hr. The proliferative response of type II cells continued to increase in 3-day and 7-day treatment groups. Labeled alveolar type I cells began to appear after 3 days, indicating that type II cells were dividing to replace damaged type I cells. Cells of the alveoli were thickened and showed vacuolization. In the bronchioles, labeled Clara cells were increased on Day 3 and Day 7 while the number of labeled ciliated cells remained near control levels throughout all time points, indicating that in bronchiolar epithelium, OOS-TMP stimulates the proliferation of Clara cells but does not damage ciliated cells. The binding of tritiated OOS-TMP to lung tissue was also examined by autoradiography. It was found that [3H]OOS-TMP binds to all regions of lung tissue. PMID- 4024108 TI - Uptake, disposition, and elimination of acrylamide in rainbow trout. AB - The uptake, disposition, and elimination of [2,3-14C]acrylamide was studied in fingerling rainbow trout exposed to 0.388 and 0.710 mg/liter [2,3-14C]acrylamide at 12 degrees C under static water conditions for 72 hr. 14C in carcass and viscera was determined at times ranging from 4 to 72 hr after the beginning of the exposure period and 4 to 96 hr after transfer of the fish to fresh flowing water for the elimination studies. Uptake of 14C was initially rapid and plateaued after 72 hr of acrylamide exposure. No appreciable bioaccumulation occurred in carcass or viscera at either exposure concentration and 14C distributed approximately equally to all tissues studied. Elimination of 14C from carcass and viscera was biphasic with a terminal half-life of approximately 7 days. 14C elimination was not uniform in all tissues studied with the most rapid elimination occurring in blood and gill and the slowest elimination occurring in muscle and intestine. In addition, 10 to 15% of the initial total 14C in carcass or viscera was nonextractable and was associated with the protein fraction of the sample at all time points in the depuration period. Approximately 20% of an ip administered dose of [14C]acrylamide was eliminated via the gills, 7% via the urine, and less than 1% via the bile in 2 hr. At least three biliary metabolites were isolated by HPLC. PMID- 4024109 TI - Acute, subchronic, and chronic toxicity studies with 3-O-demethylfortimicin A disulfate, a new aminocyclitol antibiotic. AB - The acute LD50 for 3-O-demethylfortimicin A disulfate (ODMF) in mice and rats were 419 and 778 mg activity/kg (dosages are expressed in terms of antibiotic activity (potency), rather than on a weight basis) for single-dose im administration and, 90 and 96 mg activity/kg for single-dose iv administration, respectively. No drug-related gross or microscopic lesions were found in rabbits given single iv infusions of ODMF at dosages of 10 to 400 mg activity/kg. Minimal to mild muscle irritation was seen in rabbits given im concentrations of 3.8 or 7.5% ODMF at dosages of 48 or 93 mg ODMF activity/kg. In 1-month iv studies in dogs treated with ODMF at dosages of 0.4, 1, 4, or 8 mg activity/kg/day, and in concurrent studies in rats treated with ODMF dosages of 1, 3, 6, or 12 mg activity/kg/day, treated animals remained essentially free of adverse effects. In 1-month im studies in dogs treated with ODMF at dosages of 1, 4, 8, or 16 mg activity/kg/day, no renal lesions occurred after an ODMF dosage of 1 mg activity/kg/day. Concurrent im studies in rats treated with ODMF at dosages of 6, 12, 24, or 48 mg activity/kg/day showed that ODMF dosages of 6 and 12 mg activity/kg/day did not produce renal lesions. In 6-month chronic im studies in dogs with ODMF dosages of 0.5, 1, or 4 mg activity/kg/day or gentamicin sulfate (GS) dosages of 2 mg activity/kg/day, and in concurrent studies in rats treated with ODMF dosages of 0.5, 2, or 6 mg activity/kg/day or GS dosages of 3 mg activity/kg/day, less severe local irritation and nephrotoxicity occurred after treatments with ODMF than with GS. In both rats and dogs treated by either the iv or the im route of administration, higher concentrations of ODMF and GS were found in the kidneys than in the sera. Mean serum and tissue concentrations of GS were higher than those of ODMF. Local tissue irritation and nephrotoxicity were lower with ODMF than with GS on a milligram activity per kilogram basis. PMID- 4024110 TI - Formation of N-mononitrosopiperazine in the stomach and its excretion in the urine after oral intake of piperazine. AB - Piperazine, a secondary amine widely used as an anthelmintic drug, nitrosates rapidly in vitro to form two N-nitrosamines. Anhydrous piperazine and a drug formulation were found to have a content of 0.2 to 20 micrograms of the suspected carcinogen N-mononitrosopiperazine per gram piperazine, but no detectable amounts of the carcinogen N,N'-dinitrosopiperazine. The aim of this study was to investigate the possible nitrosation of the drug piperazine in man. Thirty minutes after oral administration of 480 mg piperazine to four fasting, healthy, male volunteers, gastric juice contained 140 to 230 micrograms/liter N mononitrosopiperazine as determined by gas chromatography-thermal energy analysis. The total amount produced by endogenous formation in the stomach is estimated to have been 30 to 66 micrograms. N-Mononitrosopiperazine was not detected in blood, but was excreted in the urine, mainly in the first 6 hr (0.07 to 2.1 micrograms) with half of this appearing within 3 hr. Internal acidification of the urine did not affect the excretion or content. N,N' Dinitrosopiperazine was not found in any sample of gastric juice, blood, or urine. The excretion of piperazine was in accordance with earlier findings. Coadministration of 2 g ascorbic acid resulted in a significant but incomplete and varying inhibition of both the nitrosation in the stomach and the excretion in urine. PMID- 4024111 TI - Effect of tolbutamide and chlorpropamide on acetaldehyde metabolism in two inbred strains of mice. AB - The mechanisms by which chlorpropamide and tolbutamide disrupt acetaldehyde metabolism were studied in C57BL and DBA mice. Acute po administration of varying doses of tolbutamide or chlorpropamide 2.5 hr before a 3.0 g/kg ip dose of ethanol to C57BL and DBA mice resulted in significant elevations of blood acetaldehyde when measured 2.5 hr after ethanol dosing. Dose-response analysis revealed a significant (p less than .05) difference in ED50 values for the elevated blood acetaldehyde response to tolbutamide in DBA (60 mg/kg) and C57BL (100 mg/kg) mice. The ED50 value for potentiation by chlorpropamide of blood acetaldehyde concentration was similar (23 to 32 mg/kg) in both inbred strains. At higher doses of chlorpropamide, DBA mice displayed elevations of blood acetaldehyde nearly threefold greater than those measured in C57BL mice treated identically. Measurements of aldehyde dehydrogenase (ALDH) in hepatic subcellular fractions, obtained from both inbred strains treated with 100 mg/kg tolbutamide or chlorpropamide prior to a 3.0 g/kg dose of ethanol, revealed a 50 to 80% inhibition of the low-Km ALDH present in mitochondria. Chlorpropamide and tolbutamide did not inhibit ALDH in vitro, suggesting that metabolites of these hypoglycemic agents may be responsible for the genotypic-dependent alterations in in vivo acetaldehyde oxidation. PMID- 4024112 TI - Cadmium-induced lung injury: cell kinetics and long-term effects. AB - The effects of exposure to CdCl2 aerosols followed by hyperoxia were studied in mouse lung. Special emphasis was placed on analysis of cell proliferation following injury. Male Balb/c mice were exposed to aerosols of 4.9 micrograms Cd/liter for 1 hr while controls were exposed to water aerosols. Immediately after, half of each group was placed in 80% O2 for 6 days, while the rest were left in room air. Three endpoints were used to assess lung injury; measurement of hydroxyproline, [14C]thymidine incorporation into DNA, and histopathology. Parenchymal and bronchiolar labeling indices were determined following autoradiography. A 1-hr exposure to CdCl2 aerosols caused marked cell proliferation in the lung with the peak of cell labeling occurring at Day 5. In animals exposed to both CdCl2 + 80% O2, the cell labeling peak was delayed until Day 9. Cell differentiation studies showed a delay in the peak of type II epithelial cell and endothelial cell division when CdCl2 exposure was followed by the 80% O2 treatment. On Day 15 most of the labeled cells were identified as interstitial cells in both treated groups. Bronchiolar cell labeling was suppressed at the early time period in the Cd + O2 group. With time, the histologically visible lung lesions tended to resolve in animals exposed to CdCl2 or CdCl2 and 80% O2, whereas total pulmonary hydroxyproline remained at all times (3, 6, and 12 months) significantly higher in Cd-treated animals when compared to controls. It was concluded that acute lung injury by a toxic inhalant can be amplified if there is an initial delay in pulmonary cell proliferation following an acute insult. PMID- 4024113 TI - Taurolithocholate-induced intrahepatic cholestasis: potentiation by methyl isobutyl ketone and methyl n-butyl ketone in rats. AB - Haloalkane-induced hepatonecrogenesis can be potentiated by the prior administration of methyl isobutyl ketone (MIBK) and methyl n-butyl ketone (MBK). We investigated the possibility that these ketones could potentiate the cholestasis induced by taurolithocholate (TLC) in rats. Daily ketone pretreatment for 3 or 7 days resulted in an enhancement of the diminution in bile flow observed after TLC challenge. When the ketones were administered without TLC challenge, cholestasis was not observed; in fact, slight increases in bile flow did occur. The data suggest that MIBK may be more effective than MBK as a potentiator. Preliminary experiments with 2,5-hexanedione (HD), a metabolite of MBK and a potent potentiator of haloalkane hepatonecrosis, were included in the study. HD appeared to be a less potent potentiator of TLC-induced cholestasis. Although some ketones can potentiate cholestatic as well as hepatonecrogenic reactions, different mechanisms of action appear to be involved in these two phenomena. PMID- 4024114 TI - The effects of chronic low lead treatment and hypertension on the severity of cardiac arrhythmias induced by coronary artery ligation in anesthetized rats. AB - The aim of this study was to investigate whether chronic (1, 3, 6, 12, or 16 months) low lead (5 or 25 ppm), administered as lead acetate in the drinking water, commencing either after weaning or from conception, altered the susceptibility of the heart to arrhythmias induced by coronary artery ligation in pentobarbitone anesthetized male Sprague-Dawley rats. The cardiac effects of chronic (3 or 12 months) administration of lead (25 ppm) were also examined in spontaneously hypertensive rats. Treatment from weaning of normotensive rats with 5 or 25 ppm lead for periods of 1, 3, or 6 months had no statistically significant effect on the severity of ischemia-induced arrhythmias. Each of the groups treated from conception with 5 or 25 ppm lead for periods of 1, 12, or 16 months exhibited a higher incidence of ventricular tachycardia than the appropriate control group, but the difference was statistically significant only in the case of animals treated with 25 ppm lead for 12 months. The incidence of ventricular fibrillation was significantly higher in rats treated from conception for 16 months with 5, but not with 25 ppm lead. Spontaneously hypertensive rats treated with 25 ppm lead for 3 but not for 12 months had significantly more ectopic beats than control Sprague-Dawley rats. Lead treatment for the longer exposure periods only caused significant accumulation of lead in the blood whereas all lead treatments resulted in a marked accumulation in the bone. We conclude that chronic exposure to low concentrations of lead does not consistently alter susceptibility of the heart to ischemia-induced arrhythmias in anesthetized rats PMID- 4024115 TI - Dose-response studies of gentamicin nephrotoxicity in rats with experimental renal dysfunction. I. Subtotal surgical nephrectomy. AB - Gentamicin pharmacokinetics and nephrotoxicity have not been widely studied in animals with preexisting renal dysfunction, despite the fact that nephrotoxicity is a continuing manifestation of clinical therapy. The present study contrasted the dose-response nephrotoxicity of gentamicin in control rats with that of rats with renal insufficiency secondary to subtotal (2/3) surgical nephrectomy. Total daily doses ranging from 0 to 120 mg/kg were given in a divided regimen, every 8 hr and doses were reduced by doubling the interval in subtotally nephrectomized (Nx) rats, in proportion to impaired renal elimination on the first day of gentamicin administration. Estimates of renal function, including creatinine clearance, fractional sodium and potassium excretion, and serum creatinine and urea nitrogen, were collected after 6 and 12 days of dosing. In addition, urinary N-acetyl-beta-D-glucosaminidase excretion (6 days), in vitro renal cortical slice accumulation of tetraethylammonium (TEA) (6 days), quantified morphological lesions (12 days), and renal gentamicin concentrations (6 days) were examined. Pharmacokinetic data collected immediately after the first dose revealed a reduced gentamicin clearance and slightly reduced volume of distribution, with a corresponding prolonged half-life in the Nx rats. Based on statistical analysis of the dose-response relationships, Nx rats were functionally resistant to gentamicin nephrotoxicity after 6 days of dosing. This resistance was partially reversed by 12 days dosing, despite light-microscopic evidence of greater structural damage in the control rats. Renal parenchymal gentamicin concentrations were lower at some doses in the Nx rats, in contrast to the higher fractional reabsorption found in these rats at all doses. TEA transport was depressed at all doses in control rats but not at the lower doses in Nx rats, indicating that resistance was partially mediated at the level of the proximal tubular epithelium. This study demonstrates altered gentamicin pharmacokinetics and nephrotoxicity in a surgical model of renal dysfunction in rats. PMID- 4024116 TI - Dose-response studies of gentamicin nephrotoxicity in rats with experimental renal dysfunction. II. Polyvinyl alcohol glomerulopathy. AB - Animal studies involving concurrent pathophysiologic states, including experimental renal dysfunction, are useful for a proper understanding of the mechanisms of gentamicin nephrotoxicity and acute renal failure. This study examined gentamicin nephrotoxicity in a model of glomerular dysfunction in rats. Administration of medium molecular weight polyvinyl alcohol (PVA) produced a glomerulopathy, with characteristic accumulation of macromolecular PVA in the glomerular mesangium without altering glomerular filtration or causing proteinuria. Subsequent daily doses of gentamicin ranging from 0 to 120 mg/kg elicited a dose-response nephrotoxicity in both control and PVA-pretreated rats after 6 or 12 days of drug. Based on statistical analysis of renal clearances of creatinine, urea, sodium, and potassium; serum creatinine and urea nitrogen; urinary N-acetyl-beta-D-glucosaminidase excretion (6 days only); in vitro renal cortical transport of tetraethylammonium (TEA) (6 days); and quantified light microscopic data (12 days), PVA induced an early (6 days) sensitivity to gentamicin nephrotoxicity. By 12 days, there were no differences in the responses of control and PVA rats to gentamicin. Single-dose gentamicin clearance, volume of distribution, and half-life were not altered by PVA and renal concentrations at 6 days were generally lower in these rats. Results of TEA transport studies tend to rule out PVA-induced metabolic lesions in the proximal tubular epithelium as the mechanism for the early sensitivity. This investigation demonstrates altered gentamicin nephrotoxicity in rats with an otherwise benign glomerulopathy and, combined with similar conclusions from a related study in subtotally nephrectomized rats, presents further evidence that the underlying pathophysiologic state of the kidney is an important factor in the renal response to nephrotoxins. PMID- 4024117 TI - Adverse effect of a sucrose-based semipurified diet on development and postnatal growth of Fischer rats. AB - A commercially prepared semipurified diet (Bio-Serve No. 0006Q) composed of chemically defined ingredients was fed to male and female F344 rats before mating, to females during gestation, and to the offspring after weaning. Compared to rats treated similarly but fed a standard, cereal-based chow (Agway CR RMH 3000), offspring on the semipurified diet exhibited markedly retarded growth. At 12 weeks of age, the deficits in body weight were accompanied by decreased absolute organ weights, increased organ-to-body weight ratios, increased serum cholesterol and triglyceride levels, and development of hepatic periportal lipidosis in both male and female offspring on the semipurified diet. The deficits in body weight are explained, in part, by decreased intake of the semipurified diet, most likely attributable to its high sucrose content. Investigators are cautioned about the inadequacy of certain semipurified diets for development and postnatal growth of F344 rats. PMID- 4024118 TI - Effects of xylene isomers on operant responding and motor performance in mice. AB - Xylene, a widely used industrial solvent, is a mixture of the ortho-, meta-, and paraisomers. In this study we examined the effects of each individual isomer, as well as a commercial-grade mixture of xylenes, on two behavioral measures: (1) operant performance of 15 mice trained to lever-press under a DRL (differential reinforcement of low rates) 10-sec schedule, and (2) motor performance of mice on an inverted screen test. The 15-min operant sessions immediately followed 30-min exposures to solvent vapors (500 to 7000 ppm), or air, in static inhalation chambers. All mice were exposed to each isomer in a counterbalanced order, and the mixture was given last in all cases. Ortho-, meta-, para-, and mixed xylenes produced similar biphasic effects on response rates, and concentration-dependent decreases in reinforcement rates. The lowest significantly effective concentration for each isomer on any variable was 1400 ppm, where increases in response rates occurred. Half-maximal response rate decreases were produced by 5179 ppm (ortho-xylene) to 6176 ppm (meta-xylene). The temporal distribution of responses was only moderately disrupted, even at high concentrations. In other groups of mice, motor coordination was also disrupted by the xylenes in a concentration-dependent manner. Half-maximal effective concentrations were 2676 ppm (para-xylene) to 3790 ppm (meta-xylene). Minimally effective concentrations were 2000 to 3000 ppm, higher than those seen in the operant studies. Xylene produced pronounced behavioral actions following acute exposure and no substantial differences in overall effects, and only slight potency differences, were obtained between the individual isomers or the commercial mixture. PMID- 4024119 TI - The influence of maternal cadmium exposure or fetal cadmium injection on hepatic metallothionein concentrations in the fetal rat. AB - The ability of Cd to induce the synthesis of fetal hepatic metallothionein (MT) was investigated in rat fetuses exposed to Cd throughout gestation via the mother's drinking water or injected directly with Cd through the uterine wall on Day 18 of gestation. On Day 21 all dams were killed and fetal and maternal tissues were removed. Tissue MT, Zn, Cu, and Cd concentrations were measured. Fetal hepatic Cd concentration was increased only at the high maternal Cd exposure, whereas Zn concentration was significantly reduced by Cd exposure. Both fetal liver and kidney MT were reduced following maternal Cd exposure. Unlike maternal hepatic MT, fetal hepatic MT was not increased after maternal Cd exposure nor did the direct injection of Cd into the 18 days of gestation fetus induce fetal MT synthesis. These data suggest that fetal rat liver is incapable of synthesizing MT in response to Cd, possibly because Cd is not transported to the site of MT synthesis in the fetal system. Furthermore, neither the route of exposure, the duration of prenatal Cd exposure, nor the stage of gestation appear to account for the differences observed between fetal and adult hepatic MT induction by Cd. PMID- 4024120 TI - Comparative neurotoxicity of tubulin-binding drugs: inhibition of goldfish optic nerve regeneration. AB - Intraperitoneal or intraocular (io) injection of tubulin-binding drugs in goldfish, Carassius auratus L., inhibited axonal regeneration or restoration of functional synapses in optic axons following optic nerve crush. One eye was used to detect effects on regeneration and the other was kept intact to detect effects on maintenance of established optic circuits. Regeneration was assessed by measuring the time to reappearance of a visually evoked branchial suppression response. Three drugs, vincristine, vinblastine, and podophyllotoxin, administered semiweekly by ip injection, each inhibited regeneration at doses that did not impair maintenance of response. Similar results were previously reported for ip colchicine. Vincristine was several times more potent than podophyllotoxin or colchicine and 25 times more potent than vinblastine. Picropodophyllotoxin, an isomer of podophyllotoxin which has low affinity for tubulin, did not inhibit regeneration. The io experiments showed that maintenance of vision was reversibly inhibited by a single injection of 0.05 micrograms/g of colchicine but unaffected by 0.01 microgram/g, and that administration of the lower dose immediately following optic nerve crush inhibited regeneration. Intraocular lumicolchicine, a colchicine photoisomer which has low affinity for tubulin, did not inhibit maintenance or regeneration. In contrast, an io dose of vincristine sufficient to inhibit visual recovery also blocked maintenance of vision. Thus regeneration and maintenance effects could not be dissociated for io vincristine suggesting its mechanism of action on retinal cells is different. A conditioning lesion was shown to decrease the time to reappearance of the visually evoked branchial response following optic nerve crush, which indicates that it is a sensitive index of the rate of axonal outgrowth to the optic tectum. PMID- 4024121 TI - Procarbazine spermatogenesis toxicity: deuterium isotope effects point to regioselective metabolism in mice. AB - Procarbazine was shown to decrease spermatogenesis in male mice in a dose dependent manner. Significant decreases (44% of controls) in spermatogenesis were observed when a dose of 400 mg/kg was administered 18 days prior to determination of sperm count. Procarbazine caused no significant acute spermatocidal activity in vivo. Procarbazine-associated decreases in spermatogenesis were thus used as an index of toxicity to developing spermatid cells. Procarbazine analogs were synthesized that had deuterium substituted for hydrogen at the benzylic position, N-isopropyl-alpha-(2-methylhydrazino)-p-[alpha, alpha-2H2]toluamide (d2 procarbazine), or at the methyl position, N-isopropyl-alpha-(2-[alpha, alpha, alpha-2H3]methylhydrazino)-p-toluamide (d3-procarbazine). Spermatogenesis decreases caused by d3-procarbazine were essentially the same as with procarbazine in mice (66% of controls at a dose of 200 mg/kg), but d2 procarbazine was nontoxic to developing sperm cells (99% of control at a dose of 200 mg/kg). The decrease in toxicity caused by deuterium substitution at the benzylic position, coupled with the absence of an effect with the methyl-labeled analog, indicate the requirement for regioselective oxidative metabolism of procarbazine at the benzylic position prior to the toxic event. PMID- 4024122 TI - Ethyl acrylate-induced gastric toxicity. I. Effect of single and repetitive dosing. AB - Ethyl acrylate (EtAc) is widely used in the production of polymers and copolymers for use in the preparation of latex paints, textiles, paper coatings, and specialty plastics. EtAc caused squamous cell carcinomas and papillomas in the forestomach (nonglandular portion of the stomach) of both sexes of F344 rats and B6C3F1 mice when administered chronically by gavage. The current studies were undertaken to investigate and characterize the nature of the acute gastric toxicity caused by EtAc. Gavage administration of a single dose of 100, 200, or 400 mg/kg EtAc (in corn oil) to F344 male rats caused dose-and time-dependent mucosal and submucosal edema and vacuolization of the tunica muscularis in the forestomach and mild submucosal edema in the glandular stomach. Equivalent sc or ip doses did not produce similar gastric lesions. Treatment of rats with two or four consecutive oral daily doses (200 mg/kg each) of EtAc caused mucosal edema associated with vesicle formation, mucosal hyperplasia, submucosal edema and inflammation, and vacuolization of the tunica muscularis of the forestomach. Submucosal edema and inflammation were also observed in the glandular stomach and mucosal erosions or ulcers were observed in both portions of the stomach after repeated oral exposure to EtAc. The absence of systemic toxicity plus the dependency of gastric lesions on the gavage route of administration suggest that the EtAc-induced gastric lesions may be a consequence of localized hemodynamic changes, specifically those characteristic of a classical immediate inflammatory response to an injurious agent at the site of administration. PMID- 4024123 TI - Ethyl acrylate-induced gastric toxicity. II. Structure-toxicity relationships and mechanism. AB - Earlier studies conducted in this laboratory demonstrated that gavage administration of ethyl acrylate caused pronounced gastric toxicity in rats given single or repeated doses. The current studies were undertaken to investigate the structural, metabolic, and physical basis of this chemically induced gastric toxicity. Gavage administration of equimolar doses (2 mmol/kg) of methyl or ethyl acrylate in corn oil resulted in profound gastric toxicity in male F344 rats, while acrylic acid and n-butyl acrylate were without effect. Furthermore, gavage administration of equimolar doses of methyl propionate or ethyl propionate (saturated analogues of methyl acrylate and ethyl acrylate, respectively) as well as methacrylic acid esters were without gastric toxicity. These results indicate that structural requirements for acrylate esters to cause gastric lesions include an intact ester moiety, a double bond, and no substitution at carbon number 2. Additional studies indicate that gastric toxicity may be attributed to the intact ester molecule or to metabolite(s) other than products of carboxylesterase mediated hydrolysis (acrylic acid and alcohol) and that gastric toxicity is dependent upon both acrylate ester concentration in dose vehicle and the lipophilicity of the dose vehicle (corn oil vs water). PMID- 4024124 TI - Concentration-dependent respiratory response of guinea pigs to a single exposure of cotton dust. AB - Eight groups of guinea pigs were exposed to cotton dust at concentrations of 2 to 27 mg/m3. Each exposure was for 6 hr. The pulmonary function of each animal was assessed prior to exposure, following exposure, and 18 hr following exposure. Tidal volume decreased while respiratory frequency increased in a concentration dependent manner. These changes were amplified when the same measurements were conducted while the animals were breathing an atmosphere containing 10% CO2 in 19% O2 and 71% N2. Greatest response was noted at 18 hr postexposure. The concentration-response effects can be applied to evaluate the respiratory potencies of different cotton dusts grown under a variety of conditions. PMID- 4024125 TI - Turnover of parenterally administered zinc and cadmium and the redistribution of metallothionein bound zinc in newborn rats. AB - The whole body retention, tissue distribution and protein binding patterns of 65Zn were compared with 109Cd in newborn rats during postnatal development. One day-old pups received a single injection of either 65Zn (2.5 microCi) or 109Cd (2.5 microCi plus 1 mg Cd/kg as CdCl2). During the 22 days of age, the whole body retention of 109Cd was higher than that for 65Zn. The biological half times were 466 and 46.3 days for 109Cd and 65Zn, respectively. There were marked differences in tissue deposition of these metals. Both liver and kidney accumulated more 109Cd than other tissues while the 65Zn showed a uniform distribution, with a gradual decrease in radioactivity with age. At the time of weaning, 109Cd had accumulated mainly in liver and kidney whereas, 65Zn was found predominantly in bone and skin. The specific binding of 109Cd to hepatic MT in newborn rats did not change with growth. Although a significant amount of 65Zn initially accumulated in the MT fractions in the liver, it was transferred gradually to high molecular weight protein fractions during development. The administration of these 2 metals had no effect on the body weight, liver weight and total hepatic zinc concentration. However, a significantly high content of MT and zinc in MT fractions was detected in the livers of Cd-treated rats at 22 days of age. The results show the transfer of the essential metal, zinc from hepatic MT to other proteins and the specific binding of cadmium, the non-essential metal to MT during postnatal development in rats. PMID- 4024126 TI - Structure-nephrotoxicity relationships for para-substituted N-phenylsuccinimides in Sprague-Dawley and Fischer 344 rats. AB - N-(3,5-Dichlorophenyl)succinimide (NDPS) has proven to be one of the most nephrotoxic compounds of a series of N-(halophenyl)succinimides. Previous studies in our laboratory have demonstrated that chlorine content and position on the phenyl ring are important determinants for NDPS-induced nephrotoxicity. The purpose of this study was to investigate the relationship between the electron donating or withdrawing nature of phenyl group substituents and the nephrotoxic potential of the corresponding fungicides. Rats were administered a para substituted N-phenylsuccinimide (0.4 or 1.0 mmol/kg, i.p.) or sesame oil (2.5 ml/kg, i.p.), and renal function was monitored at 24 h and 48 h. In Sprague Dawley rats, a clear nephrotoxicity was produced by NDPS. Weak nephrotoxicity was produced by N-(4-tert-butylphenyl)succinimide (NBPS). NDPS also was the most nephrotoxic compound in Fischer 344 rats, while weak nephrotoxicity was produced by NBPS. Lipophilic character (e.g. partition coefficient) did not correlate with acute nephrotoxicity in either rat strain. These results also indicate that there is a no correlation between the electronic nature of the phenyl substituents and resulting nephrotoxicity. PMID- 4024127 TI - Lethal and behavioral effects of chlordimeform in bobwhite. AB - The 7-day LC50 of chlordimeform to bobwhite (Colinus virginianus) chicks was 2835 ppm (95% CI = 2169-3705 ppm). Bobwhite chicks fed 1000 ppm (approximately LC4) chlordimeform for 7 days ate less, weighed less, travelled farther from a fright stimulus in an avoidance test, and had significantly more groups make greater than or equal to 10 light beam interruptions in an open-field test at 8 days of age than bobwhite fed 0, 1, 10, or 100 ppm chlordimeform (P less than or equal to 0.05). Groups fed 100 ppm (P less than or equal to 0.05) and 1000 ppm (P = 0.11) for 7 days crossed more often from the shallow to deep side of a visual cliff at 8 days of age than birds fed lesser concentrations of chlordimeform. Bobwhites were retested at 15 days of age, after being fed untreated diets for 7 days following the chlordimeform diets. The 1000 ppm group still travelled greater distances in the avoidance test (P less than or equal to 0.05). But open-field and visual cliff performances were similar to controls and other treatment groups. Chlordimeform concentrations causing behavioral aberrations in bobwhite were appreciably higher than environmental concentrations following field applications of chlordimeform. PMID- 4024128 TI - Ethanol toxicity in primary cultures of rat myocardial cells. AB - The potential cardiotoxicity of ethanol (EtOH) was evaluated in primary cultures of rat myocardial cells. EtOH cardiotoxicity was assessed in the cells on the basis of cell morphology, lactate dehydrogenase (LDH) leakage, succinate dehydrogenase (SDH) activity, and beating rates. Cells were treated with EtOH at concentrations of 600, 800, and 1000 mg% for duration of 1, 4, and 24 h and then evaluated for cardiotoxicity. Vacuole formation occurred 1 h after exposure to EtOH at 800 and 1000 mg%; by 4 h, cytosolic granular material appeared in these cells. Exposure for 24 h to all concentrations of EtOH resulted in vacuole, granule, and pseudopod formation and loss of cross-striations. Significant LDH leakage occurred at 1 h and 4 h with 800 and 1000 mg% EtOH. LDH release was significantly increased after 24 h with all concentrations. SDH activity was significantly depressed after 24 h with all concentrations of EtOH. Beating rates were altered as early as 1 h after exposure to 800 and 1000 mg% EtOH. After 24 h, those cells exposed to the highest concentrations of EtOH were not beating at all. These data suggest that primary myocardial cell cultures may be used to assess the in vitro cardiotoxicity of EtOH to the myocardial cell. PMID- 4024129 TI - Manipulation of mouse organ glutathione contents I: Enhancement by oral administration of butylated hydroxyanisole and butylated hydroxytoluene. AB - Administration of either butylated hydroxyanisole (BHA) or butylated hydroxytoluene (BHT) (1000 mg/kg/day for 5 days) to male mice increased the content of reduced glutathione by 50-100% in liver, lung, duodenum and intestine. In colon, glandular stomach, spleen and kidney no effect on glutathione level was observed. BHA and BHT led also to 100-1000% induction of glutathione transferases in liver, lung (only BHA), kidney and digestive tract (except the colon); the relative increase in transferase activity was greater with 1-chloro-2,4 dinitrobenzene (DCNB) as a substrate than with CDNB in all organs investigated. The effects of BHA, administered in olive oil by gavage, on different parts of the gastrointestinal tract revealed maximum increase of the glutathione content and transferase activities in the duodenum, smaller increase of these parameters in the upper intestine and no significant effects in the lower intestine and the colon. Starving mice for 1 day decreased the glutathione content of the liver by 50% to 21.3 +/- 4.5 nmol/mg protein in controls and to 39.4 +/- 3.3 in BHA treated animals. Intravenous injection of 0.5 mmol GSH/kg restored the fed state (C: 37.4 +/- 2.8 nmol GSH/mg protein; BHA: 84.9 +/- 7.7) within 2 h. This indicates a much faster de novo synthesis of liver glutathione in BHA-pretreated animals. The mechanistic aspects of phenolic antioxidant effects on GSH metabolism are discussed. PMID- 4024130 TI - Nomenclature of biological toxins. PMID- 4024131 TI - Some previously published material relating to nomenclature of toxins. PMID- 4024132 TI - A new method for quantitating hemorrhage induced by rattlesnake venoms. PMID- 4024133 TI - Liposomal immunisation against snake venoms. AB - A method is described which produces a high, permanent antibody response following a single injection of venom. Animals (mice, rabbits, sheep) were given intravenous, subcutaneous or orally administered Nigerian Echis carinatus (carpet viper) venom which had been incorporated into sphingomyelin-cholesterol liposomes whose membranes had been stabilized by cross-linking adjacent molecules of sphingomyelin using osmium tetroxide. Before use the preparations were thoroughly dialysed to remove any unbound osmium tetroxide. Antibody levels were estimated using enzyme immunoassay. Venom treated in this way and administered i.v. or s.c. produced a powerful, sustained and protective antibody response lasting for the lifetime of a mouse. We also report the development of significant antibody responses after oral administration of liposome-entrapped but not free venom. PMID- 4024134 TI - Ochratoxin A-induced porcine nephropathy: enzyme and ultrastructure changes after short-term exposure. AB - Four pigs were treated with ochratoxin A (800 micrograms/kg) for five consecutive days. Subsequently, urine and bile were collected and kidneys were perfusion fixed unilaterally. Liver and kidney samples were examined for the distribution of ochratoxin A and metabolites in subcellular fractions and the effects of the toxin on protein synthesis and enzyme activities. Ochratoxin A and the hydrolytic product, ochratoxin alpha, were found in urine. Elevated levels of toxin accumulation in kidney (283 ng/g) compared with liver (189 ng/g) and toxin mediated reductions in protein synthesis and enzyme activities in kidney identified it as a target organ of ochratoxin toxicity. Ultrastructural investigations of kidney in toxin-exposed animals identified a process of condensation of cellular material with disappearance of membranes and continuous desquamation in the lower part of the proximal convoluted tubules. In target cells peroxisomes appeared to have lost membrane integrity and the organelles were leaking materials into the cytosol. Reduction of structural integrity was associated with an increase in the presence of catalase and cyanide insensitive fatty acid oxidase activity in the soluble kidney fractions. PMID- 4024135 TI - Characterization of two arginine ester hydrolases from Mojave rattlesnake (Crotalus scutulatus scutulatus) venom. AB - Two arginine ester hydrolases, designated AAEI and AAEII, from the venom of Crotalus scutulatus scutulatus have been investigated. The amino acid content of both enzymes were very similar and both esterases contained carbohydrate. Following treatment of AAEI and AAEII with neuraminidase, both enzymes migrated identically in two electrophoresis systems and one electrofocusing system. The esterase activities of both enzymes were optimally active in the range pH 8.0 8.5. Neither esterase hydrolyzed casein, hemoglobin (Hb) or alpha-N-benzoyl-DL arginine-p-nitroaniline (BAPNA), yet both AAEI and AAEII hydrolyzed alpha-N benzoyl-L-arginine ethyl ester (BAEE), alpha-N-benzoyl-L-arginine methyl ester (BAME), p-tosyl-L-arginine methyl ester (TAME) and acetylphenylalanylarginine methyl ester (Ac-Phe-Arg-OMe). The esterase activities of the two enzymes were inhibited by serine specific reagents and benzamide, but not by EDTA or soybean trypsin inhibitor. The Km values for each enzyme with alpha-N-benzoyl-L-arginine ethyl ester and acetylphenylalanylarginine methyl ester were determined. Neither esterase displayed thrombin-like or fibrinolytic activities. Both AAEI and AEII possessed kinin releasing activity as shown by the twitch response of an isolated rat uterus. The N-terminal sequences of AAEI and AAEII were identical and both enzymes sequences were similar to other arginine esterases from crotalid venoms. The properties of AAEI and AAEII are compared to several other arginine esterases possessing kallikrein-like activities which have been isolated from snake venoms. PMID- 4024136 TI - Tetrodotoxin derivatives in puffer fish. AB - Analysis of puffer fish tissue extracts by a fluorometric tetrodotoxin analyzer revealed the presence of three tetrodotoxin derivatives besides tetrodotoxin. The derivatives were isolated and identified as tetrodonic acid, 4-epitetrodotoxin and anhydrotetrodotoxin on the basis of mass spectral and 1H NMR measurements. The lethal potencies of 4-epitetrodotoxin and anhydrotetrodotoxin to mice by i.p. injection were 710 and 92 mouse units/mg, respectively. PMID- 4024137 TI - A sleep-inducing peptide from Conus geographus venom. AB - A novel peptide toxin, which causes a sleep-like state upon intracerebral injection in mice, has been purified to homogeneity from the venom of the piscivorous marine snail Conus geographus L. It elicits no obvious effects when injected i.p. into either mice or fish. The purified toxin is a highly acidic heptadecapeptide with no cystine residues (Lys1, Arg1, Asx2, Ser1, Glx7-8, Gly1, Ile1, Leu2). This composition is in marked contrast to those of other conotoxins, which are basic and disulphide-bridged. The N-terminal residue is Gly and the COOH-terminal sequence is Ser-Asn-NH2. PMID- 4024138 TI - Studies on the chemical modification of hemorrhagic toxin I from five pace snake (Agkistrodon acutus) venom. AB - The chemical modification of hemorrhagic toxin I (AaHI) from Agkistrodon acutus has been studied. Inactivation was observed upon modification of 3 out of 7 histidine residues with diethyl pyrocarbonate. The His residues are deblocked, accompanied by a return of activity, upon treatment with neutral hydroxylamine. The circular dichroism and fluorescence spectra of diethyl pyrocarbonate inactivated toxin and the native toxin are the same, indicating that modification with diethyl pyrocarbonate does not cause any gross change in the structure of the protein. At least one His residue may thus play an essential role in the enzyme activity. Reaction of the toxin with N-bromosuccimide abolished the enzyme activity, with modification of Trp, Tyr and His residues. The loss of Trp did not parallel the inactivation. Hydrogen peroxide, dioxane and 2-hydroxy-5-nitrobenzyl bromide treatment damaged the Trp residues, but did not affect the activity. Therefore, the modified tryptophan side chains are not essential for activity. Modification of 2.5-3.0 Tyr residues out of 9 with acetylimidazole did not affect the enzyme activity, nor did nitration of the toxin with tetranitromethane. The reactive tyrosines are apparently not essential. PMID- 4024139 TI - Characterization of the messenger RNA population coding for components of viperid snake venom. AB - Total polyadenylated messenger RNA was prepared from the milked venom glands of the South African puff adder (Bitis arietans) and translated in an in vitro translation system. The products of cell free synthesis were immunoprecipitable with puff adder venom antiserum. Treatment of these cell free products with a dog pancreas microsomal membrane preparation demonstrated the presence of signal peptides. Northern blot hybridization of total puff adder venom gland mRNA to its complementary single stranded copy DNA revealed two discrete mRNA populations coding for the major components of puff adder venom. The relative amounts of these polyadenylated mRNA sequences changed during the onset of venom synthesis, suggesting mRNA deadenylation, general endonucleolytic RNA degradation and selective degradation of high molecular weight message components. PMID- 4024140 TI - Ability of a mixture of antimyotoxin a serum and polyvalent (Crotalidae) antivenin to neutralize myonecrosis, hemorrhage and lethality induced by prairie rattlesnake (Crotalus viridis viridis) venom. AB - Mixtures containing polyvalent (Crotalidae) antivenin and antimyotoxin a serum were tested for their ability to neutralize the myotoxic, hemorrhagic and lethal activities of crude C. v. viridis venom when mixed with the venom prior to injection into white mice. A light microscopic method was used to measure the local myotoxic activity of the venom, i.e. myonecrosis index. The results show that the neutralizing ability of a 1:1 mixture of antisera for myonecrosis was 16 times that of antimyotoxin a serum alone and 63 times that of antivenin alone. There was no difference in neutralizing ability of the three ratios (2:1, 1:1, 1:2) of antivenin: antimyotoxin serum tested. Hemorrhage was measured by a new method in which the amount of hemoglobin in a muscle extract was measured after i.m. injection of test solution. The results show that the ability of a 1:1 mixture to neutralize hemorrhage was comparable to that of antivenin alone. There was no difference in hemorrhage neutralizing ability of the three ratios tested. In its ability to neutralize lethality, the 1:1 mixture was again comparable to antivenin. However, when the three different ratios of antisera were tested for neutralization of lethality the 2:1 and 1:1 ratios were as effective as antivenin alone, whereas the 1:2 ratio (antivenin: antimyotoxin serum) was less effective than antivenin alone. Thus the addition of antimyotoxin a serum to antivenin in equal proportions greatly improves the neutralization of the myotoxic activity of C. v. viridis venom and does not decrease the ability of antivenin to neutralize hemorrhage and lethality. PMID- 4024142 TI - Detection of tetrodotoxin-like compounds in two species of puffer fishes (Lagocephalus lunaris lunaris and Fugu niphobles). AB - The toxins in the muscle, skin and liver of the puffer fish Lagocephalus lunaris lunaris and those in the skin and liver of another puffer fish Fugu niphobles were purified by successive column chromatography on activated charcoal, Bio-Gel P-2 and Bio-Rex 70 and analyzed by electrophoresis and thin layer chromatography. Although, regardless of the tissues and species, tetrodotoxin was predominant and accounted for more than 90% of the total toxins, the following minor toxins were newly detected; toxin A and toxin B in L. lunaris lunaris and toxin C in F. niphobles. Since these minor toxins, like tetrodotoxin, were positive to the Weber reagent and 10% KOH, but negative to 1% H2O2, they were assumed to be tetrodotoxin-like compounds. Interestingly, the electrophoretic and thin layer chromatographic analyses showed that toxin A and toxin C are probably identical with AFT3 and AFT1, the minor toxins in the crab Atergatis floridus from Chiba, Japan, respectively. PMID- 4024141 TI - Staphylococcal alpha toxin induced changes in the electroencephalogram of the rat. AB - Staphylococcal alpha-toxin at 1 microgram and 10 micrograms was injected into the right lateral ventricle of the brain of conscious, unrestrained rats. Clinical behavior and changes in EEG patterns were monitored. Clinical behavior attributed to alpha-toxin intoxication consisted of intermittent periods of stretching, tremors, convulsions and 'barrel rolling'. The EEG patterns, selected from recordings obtained during quiescent periods of behavior, demonstrate focal spiking, with and without recruitment, slow waves, spindling and complex spikes. We conclude that the central nervous system is a critical target for the lethal action of alpha-toxin. PMID- 4024143 TI - Absence of toxin-producing parapodial glands in amphinomid polychaetes (fireworms). AB - Amphinomid polychaetes (fireworms) have been responsible for 'bristleworm stingings' and their large setae are reputed to be filled with toxin. The setae and parapodia of Eurythoe complanata, Chloeia flava and Pherecardia striata were examined using histological and scanning electron microscope techniques. No evidence was found for hypothesised toxin-producing glands communicating with the parapodial setae. Setae were hollow, but empty. It is suggested that these polychaetes are urticating rather than toxic. PMID- 4024144 TI - Comparative studies on three rattlesnake toxins. AB - Toxins from the venoms of Crotalus durissus terrificus, Crotalus s. scutulatus and Crotalus viridis concolor were compared using gel filtration, ion-exchange chromatography on DEAE-Sephacel and denaturing and non-denaturing polyacrylamide gel electrophoresis. The three heterodimeric native toxins behaved similarly on each of the separation media, except that the C. d. terrificus toxin displayed a pronounced tendency to dissociate on DEAE-Sephacel, even in the absence of urea. In the presence of 6M urea, subunit dissociation was quantitative for all three toxins. Recombination of purified subunits resulted in toxins which eluted from the gel filtration column in identical fashion to native toxins. Non-denaturing polyacrylamide gel electrophoretic patterns of recombined toxins actually showed greater band resolution than did the native toxins. Six hybrid toxins were generated on polyacrylamide gels from cross-combinations of purified subunits, each with different mobilities than the parental toxins. Mobilities of the hybrid toxins depended principally upon the mobilities of the basic subunits. All three purified native toxins showed comparable LD50's in female mice (0.039-0.061 micrograms/g). The C. d. terrificus acidic X C. s. scutulatus basic hybrid toxin showed toxicity identical to that of the C. s. scutulatus recombined toxin. Phospholipase activity is associated with the basic subunit in all three toxins. Intact toxins show a distinctive lag in phospholipase activity which is not seen with purified basic subunits alone. These results indicate that the principal toxins in these three venoms are homologous. PMID- 4024145 TI - A combination fluorescence assay and Folin-Ciocalteau phenol reagent assay for the detection of paralytic shellfish poisons. AB - Paralytic shellfish poison (PSP) profiles of crude shellfish extracts were determined by linear gradient elution from a Bio-Rad AG-50-X4 strong cation exchange resin mini-column. STX, GTX2 and GTX3 were detected by fluorescence assay. NeoSTX and GTX1/GTX4 were detected with a Folin-Ciocalteau phenol reagent assay. The major toxicity associated with extracts of Mytilus edulis and Mya arenaria collected during a 1972 red tide off Hampton, New Hampshire, was due to the presence of GTX1/GTX4, with some activity associated with neoSTX, GTX2 and GTX3. STX was also present. Correlations to mouse toxicity are provided. PMID- 4024146 TI - [Alterations in the coagulation mechanisms of patients bitten by Bothrops asper (Terciopelo)]. AB - Blood from eighteen patients bitten by B. asper were studied for effects on coagulation. All showed alterations in the levels of fibrinogen and of factors II, V, VIII, IX, X and XI, as well as in anti-thrombin-III and plasminogen. The number of platelets and the concentrations of factors VII and XII did not show significant variations in comparison with the controls. The biological assay of fibrinogen, the quantitation of fibrinogen degradation products and of factor II and the general coagulation tests, such as prothrombin and partial thromboplastin times, showed a good correlation with the severity of the envenomation. In snakebites by B. asper there is a severe hypofibrinogenemia, with fibrin degradation by activation in the fibrinolytic system and with activation and consumption of factor II. Intramuscular emergency treatment with small quantities of antivenom did not prevent the above noted alterations in coagulation. PMID- 4024147 TI - Interaction of streptolysin-O with biomembranes: kinetic and morphological studies on erythrocyte membranes. AB - The kinetics of lytic events caused by the bacterial cytolytic toxin streptolysin O (SLO) in red blood cells was examined using erythrocytes of several species of defined age and at different temperatures, by measurement of hemoglobin and ATP release. Lysis required much lower doses of SLO than hitherto described in the literature. Resistance to SLO varied within the different species, with the reaction temperature and increased with storage time (in vitro age). When erythrocytes treated with SH-activated SLO were examined in the electron microscope after negative staining or freeze-etching, ring- and arc-shaped structures were observed on the outer surface of their membranes. Identical, ring and arc-shaped structures were also observed in SH-activated SLO solution alone. The findings indicate that SLO-SH complexes are formed upon activation and are not an SLO-cholesterol complex, as cholesterol was not detectable. These results led to a morphological model which proposes that the ring- and arc-shaped SLO complexes hitherto described are polymerized forms of single SLO molecules. A functional model which suggests a mode of action of SLO-SH complexes is also discussed. Analysis of freeze-fracture micrographs of SLO-treated erythrocytes revealed no indication of formation of membrane pores through which cell lysis could occur. Aggregation of inner membrane particles, however, indicated that the membrane integrity had been severely altered. Thus, hemoglobin and ATP most probably permeate the membrane at fragile areas. PMID- 4024148 TI - A non-proteinaceous toxin from the venomous spines of the lionfish Pterois volitans (Linnaeus). AB - The venomous spines of P. volitans contain a non-proteinaceous ichthyotoxin of low molecular weight. This toxin could be isolated only from spines excised from the living fish; the toxin is apparently destroyed following death, as the extracts of the spines of the dead fish were non-toxic. PMID- 4024149 TI - Toxic effects of the soluble skin secretion from the Arabian Gulf catfish (Arius thallasinus, Ruppell) on plasma and liver enzyme levels. AB - Injection of skin toxin into the marginal ear vein of rabbits resulted in acute respiratory distress and convulsive movements, followed by death within 7 min. Significant increases in total plasma lactate dehydrogenase and the hepatic and cardiac derived isozymes and in glutamic-oxaloacetic and glutamic-pyruvic transaminase activities were observed in animals receiving toxin. Lower doses of toxin increase the survival time and enzyme levels in plasma. Skin toxin produces a time dependent toxic effect on the liver and heart. PMID- 4024150 TI - Trichothecene structure and toxicity to the green alga Chlorella pyrenoidosa. AB - Using the paper-disk method with Chlorella-seeded agar plates, 15 acetoxyscirpenol, HT-2 toxin, acetyl T-2 toxin and neosolaniol inhibited growth at a concentration of 1 mg/ml, whereas verrucarol, T-2 tetraol, nivalenol, fusarenon-X, deoxynivalenol and 3-acetyldeoxynivalenol were inactive. Taking into account that verrucarin A, roridin A, T-2 toxin and diacetoxyscirpenol had previously been found to strongly inhibit Chlorella growth, esterification at R15 appears to be important for growth inhibitory activity. The most active agents are also esterified at R4. Inhibition of protein synthesis appears to be involved in the toxicity. PMID- 4024151 TI - Rapid cytotoxicity testing using a semi-automated protein determination on cultured cells. AB - A rapid cytotoxicity screening procedure that measures the inhibition of protein synthesis in cultured cells is described. Cells are cultured in 96 microwell plates, test agents are added to the cultures, and the protein content of the cultures is then determined in the microwells using a modification of the Coomassie blue dye complex method. Absorbances in the wells are determined by scanning the plate in a microplate reader. The method is sensitive, rapid, reproducible and inexpensive, enabling the large-scale screening of potential toxicants. Results of the application of the procedure to the measurement of toxicity of 6 surfactants and 6 divalent metal ions are presented. PMID- 4024152 TI - Effects of gentamicin on renal function in isolated perfused kidneys from male and female rats. AB - The isolated perfused rat kidney was used to determine whether sex differences in gentamicin nephrotoxicity are related to intrinsic differences in renal response to gentamicin. Acute exposure to gentamicin decreased fractional reabsorption of water and electrolytes without changes in glomerular filtration rate in both sexes. Gentamicin decreased the tubular reabsorption of lysozyme but not glomerular permeability to lysozyme. No sex differences in renal responses were observed following in vitro exposures to gentamicin, suggesting that sex differences in susceptibility to gentamicin in vivo may be attributable to extrarenal factors, such as pharmacokinetics. PMID- 4024153 TI - Effects of fluoride on screech owl reproduction: teratological evaluation, growth, and blood chemistry in hatchlings. AB - The effects on reproduction in screech owls (Otus asio) of chronic dietary sodium fluoride administration at 0, 40, and 200 ppm were examined. Fluoride at 40 ppm resulted in a significantly smaller egg volume, while 200 ppm also resulted in lower egg weights and lengths. Day-one hatchlings in the 200 ppm group weighed almost 10% less than controls and had shorter crown-rump lengths. No gross abnormalities were apparent. Skeletal clearing and staining revealed significantly shorter tibiotarsus lengths in the 40 ppm and 200 ppm groups and a shorter radius-ulna length in the 200 ppm group. By 7 days of age, body weights and lengths did not differ from controls, but the tibiotarsus in the 200 ppm group remained shorter. No significant differences were detected in hematocrit, hemoglobin, plasma calcium or alkaline phosphatase. Plasma phosphorus levels were higher in the 40 ppm group than in controls. These results, in combination with the findings of Pattee et al. [25], revealed significant impairment of overall reproduction, suggesting that sodium fluoride could cause slight to moderate reproduction disorders in owls in fluoride-polluted areas. PMID- 4024154 TI - Uric acid levels in plasma and urine in rats chronically exposed to inorganic As (III) and As(V). AB - The effect of inorganic arsenic (III) and arsenic (V) on renal excretion and plasma levels of uric acid was examined in rats. Oral administration of 1200 micrograms As/kg/day for 6 weeks diminished uric acid levels in plasma by 67.1% and 26.5% of control after the administration of As(III) and As(V), respectively. Renal excretion of uric acid was significantly reduced during the first 3 weeks following As (III) administration, with a subsequent increase to approach control values at the end of the treatment. When As(V) was administered, the diminution in renal excretion was significant at 6 weeks. PMID- 4024155 TI - Cytotoxic action of rat alveolar macrophages for ozone-exposed lung fibroblasts. AB - The objective of this study was to determine if exposure of cultured rat lung fibroblasts to O3 would trigger a subsequent attack by rat alveolar macrophages (AM). Fibroblasts labeled with [3H]proline (3HPR) were exposed to O3 (0, 0.74, 1.35, 2.46 or 4.48 ppm) for 1 h. AM were added (5:1, AM: fibroblast) and after 2, 24, 48, 76 and 96 h of co-culture, loss of 3HPR was measured as an index of AM induced injury. Fibroblasts exposed to O3 and co-cultured with AM lost significantly more 3HPR than without AM co-culture. The results suggest that O3 injury to the lung may be mediated in part through an attack by AM upon O3 injured fibroblasts. PMID- 4024156 TI - Properties and toxicity of airborne wood dust in wood-working establishments. AB - The total suspended dust levels, particle shape and size distributions and metal concentrations (Cd, Cr, Cu, Fe, Mn, Ni, Pb and Zn) of wood dust in the breathing zone of 3 small wood-working establishments were monitored. In vitro culture assay indicated that the mortality of alveolar macrophage was related to the metal content of dust collected from these 3 workplaces. PMID- 4024157 TI - Tumorigenic and toxic effect of O,S-dibenzoyl thiamine hydrochloride in prolonged dietary administration to rats. AB - The chronic toxicity of O,S-dibenzoyl thiamine hydrochloride (DBT) was studied by prolonged dietary administration to rats at dosages of 1000 and 10 000 ppm. The study confirmed the low toxicity of this compound and absence of carcinogenicity. PMID- 4024158 TI - The effects of ethanol on the kinetics of toluene in the perfused rat liver. AB - In the isolated perfused rat liver as a metabolizing system, ethanol (17.1 mM) added directly to the perfusion medium decreased the extraction ratio of toluene (concentration range 0.2-16.4 microM) by 17-33%. The Michaelis-Menten constant, Km, was calculated to 3.9 microM and the maximum elimination rate, Vmax, to 10.8 and 11.4 nmol/min/g in the absence and presence of ethanol, respectively. The results indicate that the inhibitory effect of ethanol on the elimination of toluene is competitive. In a physiologically operating system, it must be taken into account that the elimination of toluene, apart from being influenced by the hepatic blood flow, may also be affected by lowered enzyme capacity for the metabolism of toluene. PMID- 4024159 TI - In vitro cytotoxicity of glycol ethers and oxidation products in CHO cells. AB - The cytotoxicity of several glycol ethers and of some of their oxidation products, the corresponding alkoxy acetates, was compared in Chinese hamster ovary (CHO-K1) cells without metabolic activation. Cytotoxicity was measured in terms of cloning formation ability, and EC50 values (concentrations allowing 50% of the seeded cells to form colonies) were estimated. The results, in the case of unmetabolized glycol ethers tested, showed an increase in toxicity with increasing chain length. The cytotoxicity of the corresponding alkoxy acetates, however, did not exhibit a trend in parallel with the chemical structure. 2 Methoxypropionic acid was somewhat less cytotoxic than the alkoxy acetic acids investigated. It is concluded that gross cytotoxicity to dividing cells is not the predominant mechanism for the teratogenicity or myelotoxicity and testes toxicity of methoxy- and ethoxyethanol, which produce these effects after oxidation to their corresponding alkoxy acetates. PMID- 4024160 TI - Teratogenesis study of dioxane in rats. AB - The industrial solvent dioxane (1,4-diethylene dioxide) was evaluated for teratogenic potential in Sprague-Dawley rats. The compound was administered on days 6-15 of gestation by gavage (0, 0.25, 0.5 and 1.0 ml/kg/day). A slight maternal toxicity, as evidenced by reduced weight gain, was observed with 1.0 ml/kg. Animals were killed and subjected to uterine examination on day 21 of pregnancy. There were no differences between control and dioxane-treated groups in implantation numbers, live fetuses, postimplantation loss or major malformations. Embryotoxicity, manifested by reduced fetal weight, occurred only at the highest dose level. PMID- 4024161 TI - Cyanoacrylate adhesive for attaching Ralph knives to holders. PMID- 4024162 TI - A simple device to eliminate static electricity while sectioning paraffin. PMID- 4024163 TI - [Use of electrons above 20 MeV for reduction of radiation exposure]. AB - After many years of clinical application of a 42 MeV betatron, the following indications were found for deep therapy with electrons above 20 MeV: tumors situated in the brain, mediastinum, kidney, liver, bladder, rectum, as well as peripheral tumors situated in different body regions. For eight different cases, the total body exposure and the radiation exposure of some risk organs was calculated for an irradiation with electrons alone, a combination of electrons and photons, an irradiation with 42 MeV X-rays and with Co-60 gamma rays alone. All these calculations were based on a most favorable irradiation technique. The results showed that electrons up to 40 MeV can spare more than 30% of the total body dose; a combination of electrons and photons allows a reduction of the total dose of about 15% as against that of photons alone, which makes possible a better conservation of skin. This total dose reduction corresponds to that achieved by the substitution of ultrahard X-radiation for Co-60 gamma radiation in deep therapy. The radiation exposure of risk organs can often be reduced by the use of electrons, too. Thus electron deep therapy shows to be justified for the mentioned tumor cases. This is also confirmed by clinical experience. PMID- 4024164 TI - [The immune status of patients with irradiated testicular neoplasms]. AB - The authors present the results of investigations of the immune reactivity of 72 patients irradiated for testicle tumors. The responses to tuberculin and DNCB (2.4-dinitrochlorobenzol) were examined before the treatment, within twelve months after radiotherapy and three years after radiotherapy and when metastases appeared. After radiotherapy, the number of positive responses was slightly decreased in both examination methods, but the difference was in no case significant. Patients with metastases showed a significantly decreased response to DNCB compared to the results obtained before radiotherapy. 5.6% of the patients had suffered from herpes zoster. The incidence of other infective diseases was not increased. The conclusion is drawn that the moderate immunosuppression caused by radiotherapy does not exert any influence on the further way of living of patients with testicle tumors. PMID- 4024165 TI - [Dose rate constant and radial dose function of an iodine 125 radiation source in various substances]. AB - The dose distribution around an isotropic, point radiation source can be expressed by the dose rate constant, the quadratic law of distance, and a radial dose function which depends on the absorption and scatter processes occurring in the surrounding material. The radial dose function and the dose rate constant of a point iodine-125 source can be represented in a clear and rather exact manner as simple functions of the linear attenuation and energy absorption coefficients, because the average photon energy does not considerably vary with the growing distance from the source. This representation is in contrast with some functions defined in a distance of 1 cm, in conformity with the definition of the dose rate constant in the air according to DIN 6814, part 3. PMID- 4024166 TI - Non-invasive investigations of the growth kinetics of a solid experimental tumor (sarcoma-180). AB - The investigations reported were performed to test applicability of non-invasive methods for the measurement of the parameters determining the growth of a solid experimental tumor and to measure these data for the tumor system sarcoma 180/NMRI-mice. It could be shown that non-invasive methods can be used for the measurement of tumor growth, especially the fraction of proliferating cells (growth fraction) which is of special importance for tumor therapy. For the tumor system under investigation, the growth is completely determined by an exponential decrease of the growth fraction. PMID- 4024167 TI - Hemopoiesis in mouse heterozygous for the W trait. Difference in postirradiation recovery related to the defect in formation of transient endogenous spleen colonies. AB - The hemopoietic regeneration following midlethal irradiation in Wv/+ mice had similarly biphasic kinetics as in their hematologically normal +/+ littermates. The first abortive phase of regeneration was either severely reduced (formation of transient endogenous spleen colonies, reticulocyte count, granulocyte count) or absent (spleen and femur cellularity, platelet count, PCV) in Wv/+ mice, when compared to +/+ mice. The second phase leading to permanent recovery of hemopoiesis was in Wv/+ mice delayed in time. Moreover, although to a lesser extent the values of spleen and femur cellularity, PCV and platelet count were decreased in Wv/+ mice. Postirradiation bleeding, which stimulated particularly the 1st phase of regeneration both in Wv/+ and +/+ mice did not lead to the minimization of differences between above two genotypes. It is suggested that the observed differences in the abortive regeneration between Wv/+ and +/+ mice are primarily dependent on the presence in Wv/+ mice of selective defect of transient endogenous colony forming units (TE-CFUs). Moreover, it is possible that the differences in the second phase of regeneration leading to permanent recovery are secondarily dependent on the TE-CFUs defect, as most probably the TE-CFU is the step in stem cell differentiation to mature cells. PMID- 4024168 TI - The effects of X-ray irradiation of the head region of eight-day-old rats on the development of molar and incisor teeth. AB - The effects of irradiation on the development of molars and incisors up to the age of 57 days was studied applying locally a single dose of 9.6 Gy of X-rays to the head region of eight-day-old female rats. Radiography of jaws revealed the absence of the third molar in all irradiated rats, as a result of germ stunting which was, at the moment of irradiation, in the phase of histodifferentiation. In the case of the first and second molar, being at the time of irradiation in the phase of root formation, changes were noted in the development and morphological features of the roots. In animals sacrificed 18 days after irradiation, the radiographs of jaws showed a break in the continuity of the incisors located under the mesial root of the first molar. In all animals the break in continuity of the incisors became macroscopically visible between the 28th and 42nd day after irradiation. 15 days after the loss of incisors, the incisival functional occlusion was restored in all animals. PMID- 4024169 TI - [Bone scintigraphy for the staging of lymphogranulomatosis?]. AB - The importance of bone scintigraphy for the classification of stages of lymphogranulomatosis is judged differently, the indications in literature are not unanimous. The high sensitivity of this method is uncontested, but it is said to be not very reliable in the exclusion of a bone manifestation because of its low specificness. Bone scintigraphy demonstrates a disturbance in bone metabolism; in clinical examination this has to be checked by X-ray view in order to exclude not tumor-induced reasons for the increased or decreased concentration. In a prospective study we have investigated if this combined radiologic approach allows to use scintigraphy in the classification of stages. Four out of 23 patients in stage I showed a tumor-suspicious scintigram which was confirmed by X ray examination within 1 1/2 years in two patients. One quarter of 133 patients in stage II and III had a pathologic scintigram. In 34 out of 36 patients who could be followed up, this was confirmed later on by an X-ray finding in the same site. 15 out of 36 patients in stage III with initially normal scintigram showed a conversion to a tumor-suspicious scan during the later course of the disease. The tumor-suspicious scintigraphy found at the time of classification of stages has been confirmed later on by X-ray examination in 91% of our series. So, scintigraphy may be considered to be valuable for the classification of stages. Furthermore the conformity of tumor-suspicious scintigram and bone marrow biopsy was investigated. Whereas in 62% of patients with M+ a bone manifestation could be demonstrated by scintigraphy, only 46% of patients with scintigraphic 0+ showed a histologic manifestation in bone marrow. Consequently, bone scintigraphy cannot be used to demonstrate or to exclude a manifestation in bone marrow. As the metabolism is modified by therapy in case of a demonstrated bone manifestation, scintigraphy should be a sensitive parameter in these cases, too, for an early indication of response to cytostatic treatment. The scintigram became normal in 46 patients coming to a complete remission; eight out of nine patients the scintigraphic findings of whom became worse were non-responders. Five out of twelve patients with unchanged scintigram came to a remission. A normalizing scintigram indicates a response to therapy, whereas a deterioration suggests a non-response. Bone scintigraphy can also be used to judge the success of a cytostatic therapy. PMID- 4024170 TI - [NMR-diagnosis in radiotherapy?]. AB - The results of NMR tomography obtained hitherto in the imaging of malignant tumors are presented in order to show that this new method is of great importance for radiotherapy. A quantification of radiotherapy and chemotherapy seems possible with the aid of NMR diagnosis, as vital and necrotic tumors zones as well as radiation effects in the tumor and in sound tissue can be visualized. PMID- 4024171 TI - [An online monitoring system for the control of field homogeneity in accelerators]. AB - For checks and service an online monitoring-system consisting of 10 Si photoelements will be described. It allows a very simple and fast control of field flatness in therapy-accelerators. PMID- 4024172 TI - Delay in referral of patients with ruptured aneurysms to neurosurgical attention. AB - Aneurysmal subarachnoid hemorrhage is a neurosurgical emergency. Early medical intervention is axiomatic for minimizing rebleeding and ischemia from vasospasm and achieving optimum results. The purpose of this study was to document the length and causes of the delay in referral which occur in patients following aneurysmal subarachnoid hemorrhage. The case histories of 150 consecutive patients admitted to The University of Iowa with proven ruptured aneurysms were studied. Medical records from The University of Iowa and referring hospitals were reviewed, and patients, families, and referring physicians interviewed. Overall, only 36% were referred within 48 hours of their first clear cut, recognizable sign or symptom of subarachnoid hemorrhage. Median time to referral was 3.6 days. Delay was due to physician diagnostic problems in 37%, delayed referral policy in 23%, unstable patient condition in 7%, failure of patients to recognize severity of illness in 8%, and logistical reasons in 12%. These data suggest that a large proportion of patients have a delay in achieving definitive neurosurgical care following aneurysm rupture, and that for the most part this delay is avoidable. More emphasis must be placed on public health and primary physician education regarding subarachnoid hemorrhage. PMID- 4024173 TI - Subarachnoid hemorrhage: epidemiology, diagnosis, management, and outcome. AB - A population-based study of primary subarachnoid hemorrhage in Auckland (population 829,454), New Zealand, identified 180 cases in a two-year period. This represented an age adjusted incidence rate of 10.5 and 18.3 per 100,000 for men and women respectively. Sixty-eight percent of all cases had a proven intracranial aneurysm or arteriovenous malformation, 15% had negative angiographic findings and in the remaining 17%, the presence or absence of a localized lesion was unknown since neither angiography nor autopsy were performed. Twenty-six patients (15%) died before hospitalization and a further 36 patients (20%) died within 48 hours of onset. Only 94 patients (53% of all patients registered) were fit enough to undergo angiography. A surgical operation was carried out on 60 of the 68 patients in whom an aneurysm was confirmed at angiography. The overall case fatality rate was 36% within the first 48 hours, 43% in the first week and 57% at both six months and one year. The high early case fatality rates are similar to those found in previous population-based studies, suggesting that despite the major advances to individual patients from technological advances, the potential contribution of hospital management to the reduction of subarachnoid haemorrhage mortality rates is likely to be limited. PMID- 4024174 TI - Subarachnoid haemorrhage in the rat: angiography and fluorescence microscopy of the major cerebral arteries. AB - A subarachnoid haemorrhage (SAH) in the rat was produced by the injection of blood via a previously implanted catheter connected to the cisterna magna. Repeated angiographical examinations of the vertebro-basilar arteries revealed a biphasic vasospasm with a maximal acute spasm at ten minutes and a maximal late spasm at two days after cisternal blood injection. Fluorescence microscopical examination of the major cerebral arteries at day two after the SAH revealed a reduction in the fluorescence intensity and in the number of histochemically visible sympathetic nerve terminals. PMID- 4024175 TI - Epidemiologic features of isolated syncope: the Framingham Study. AB - To obtain epidemiologic information regarding syncope, 2336 men and 2873 women aged 30 to 62 years at entry to the study were evaluated for syncope. During 26 years of surveillance, evidence of cardiac or neurologic morbidity and mortality was also recorded. At least one syncopal episode was reported by 71 (3.0%) of the men and 101 (3.5%) of the women during the course of the study. Criteria for isolated syncope (i.e., transient loss of consciousness in the absence of prior or concurrent neurologic, coronary, or other cardiovascular disease stigmata) were met by 56 (79%) of the 71 men and by 89 (88%) of the 101 women with syncope. During 26 years of follow-up isolated syncope was not associated with any excess of stroke (including transient ischemic attack) or myocardial infarction. Similarly, isolated syncope was not associated with any excess of all-cause or cardiovascular mortality (including sudden death). PMID- 4024176 TI - Hemodynamics in hemorrhagic infarction--an experimental study. AB - Using the canine thalamic infarction model, hemodynamics, CO2 responses and thalamic EEG changes were studied in 7 dogs. Of the 7 animals, 4 showed hemorrhagic infarction and 3 did not, following recirculation after 6 hours of vascular occlusion. 1) The rCBF threshold for producing hemorrhagic infarction when recirculation following 6 hours of vascular occlusion was approximately 50% of the pre-occlusion level. 2) rCBF of the animals showing hemorrhagic infarction included hyperperfusion due to recirculation, and then fell to a level below the pre-occlusion level in a relatively short period. The CO2 response became disturbed both during occlusion and after release of occlusion. Thalamic EEG was nearly flat during vascular occlusion and recovery was not seen following recirculation. 3) rCBF of the animals not showing hemorrhagic infarction recovered rapidly to the pre-occlusion level due to recirculation. The CO2 response was somewhat disturbed during occlusion, but recovered following recirculation. Thalamic EEG was well preserved both during occlusion and after release. PMID- 4024177 TI - Chronological changes in spontaneous intracerebral hematoma--an experimental and clinical study. AB - A model of intracerebral hematoma that closely resembles the state in humans after spontaneous intracerebral hematoma was developed. Sequential changes in experimental intracerebral hematomas were compared with the in vivo findings in spontaneous intracerebral hemorrhage. The clinical series consisted of 28 patients with spontaneous intracerebral hemorrhage observed by CT during their natural course from 1976 through 1978. The experimental series consisted of 26 adult mongrel dogs with intracerebral hematoma near the basal ganglia studied by CT and histological examinations. In neither the clinical nor the experimental series was the time of decrease in density beginning in the periphery of the hematoma or the first appearance of ring enhancement and its concentric concentration toward the center of the hematoma affected by the size of the hematoma. In the experimental series, the tissue reaction near the periphery of the intracerebral hematoma showed constant processes: First, a necrotic layer appeared; this was then replaced by immature connective tissue with newly formed vessels and argentophilic fibers, and finally the immature layer was gradually transformed into mature connective tissue with collagenous fibers. Ring enhancement was accompanied by the appearance of immature connective tissue and capillaries. This process of change was also unrelated to the size of the hematoma. The following correlations were suggested from the chronological observation of CT images and the histological appearance: 1) acute stage - homogeneous high density extending to the periphery, appearance of the necrotic layer; 2) subacute stage - decreased density spreading from the periphery and formation of ring enhancement, appearance of immature connective tissue with argentophilic fibers; 3) chronic stage - concentric concentration of ring enhancement and development of mature connective tissue with collagenous fibers. PMID- 4024178 TI - Cerebral edema associated with craniectomy and arterial hypertension. AB - The present studies were performed to determine whether cerebral edema will develop as a consequence of arterial hypertension and/or craniectomy. Arterial hypertension was induced for 30 minutes by inflation of a balloon catheter situated in the descending aorta, and a parietal craniectomy was performed. The cerebral edema noticed was evaluated by macroscopic and microscopic observations, BBB permeability of HRP and Evans blue and water content. In addition, ICP was measured in the cisterna magna and ICPP by a catheter-tip transducer. In arterial hypertension or craniectomy alone, some small areas of Evans blue extravasation with increased water content were seen in the cortex, which corresponded to the occipito-parietal parts of the arterial boundary zones. In contrast, when arterial hypertension was combined with craniectomy, these lesions extended further into underlying white matter with increased water content. Forty-eight hours later, extensive brain edema with a shift of midline structures developed on the side of craniectomy which differed from that in arterial hypertension or craniectomy alone. It is suggested that some hydrostatic pressure gradients, particularly between blood vessel and surrounding extracellular space and among different areas within the brain parenchyma, may play an important role in the development of brain edema. PMID- 4024179 TI - The effects of extreme hemodilutions on the autoregulation of cerebral blood flow, electroencephalogram and cerebral metabolic rate of oxygen in the dog. AB - The effects of profound (hematocrit value, Ht 20%) and extreme (Ht 5%) hemodilutions on the relationship between the mean arterial pressure (MAP) and the cerebral blood flow (CBF) were studied in pentobarbital-anesthetized dogs. A regression line was found between the CBF and Ht values during normotensive hemodilution (MAP 100 torr): CBF (ml/100g X min) = -98.9 log Ht (%) + 195.5 (p less than 0.001). The CBF was increased by hemodilution, but the range of its autoregulation was narrowed, suggesting a progressive susceptibility of CBF to blood pressure with hemodilution. The electroencephalogram (EEG) was not significantly changed by hemodilution within the range of the CBF autoregulation, below which it became slowed. In contrast, the cerebral metabolic rate of oxygen (CMRo2) was decreased by hemodilution even within the range of the CBF autoregulation, while there were no significant differences in CMRo2 values between MAPs of 100 and 40 torr. Thus, the brain function in terms of the EEG seemed to correlate more with the autoregulatory mechanism of the CBF than with the CMRo2 value in the hemodiluted states. PMID- 4024180 TI - Cellular actions of halothane on cat cerebral arterial muscle. AB - The effects of halothane on intracellular membrane potential (Em) and force development in cat MCA were studied. Halothane (0.07-0.14 mM/1) relaxed isolated MCA which had developed myogenic tone. Measurement of Em showed that halothane depolarized this preparation in a dose-dependent fashion in the face of vessel relaxation, demonstrating uncoupling of electrical and mechanical activity. Halothane markedly inhibited the contractile effects of histamine and serotonin suggesting that, apart from its direct action on cerebral arterial tone, it also blunts the action of vasoactive agents. When this preparation is partially depolarized from -62 to -50 mV with excess K+, halothane, while having only a small (1.2 mV) additional depolarizing effect, consistently elicits contraction rather than relaxation. Thus, the action of this particular volatile anesthetic on cerebral arteries can depend upon the resting level of Em. These studies indicate that halothane relaxes myogenic tone in cat MCA by an intracellular mechanism, but that the direction of its effect (i.e., relaxation vs. contraction) may depend upon the prior level of Em and muscle cell activation. PMID- 4024181 TI - Dye injection method for the demonstration of territories supplied by individual perforating arteries of the posterior communicating artery in the dog. AB - Various reported methods to demonstrate the territory supplied by an intracranial artery are designed to deal with major cerebral arteries or a group of perforating arteries. We have devised a technique to demonstrate the area supplied by individual small perforating arteries using different dyes with gelatin. A temporal craniectomy was made in the dog and the posterior circle of Willis was exposed via a subtemporal route under the operating microscope. After a portion of the posterior communicating artery including one perforating artery was trapped with clips, dye was injected through the cannule. The animals were immediately sacrificed and studied. The area supplied by an individual perforating artery occupied a relatively large and distinct area, and when two dyes for two different perforators were used, no significant overlapping of the stained territories was seen. This method is useful for the study of focal cerebral ischemia caused by occlusion of a fine perforating artery and in particular it will serve to clarify the importance of preserving each perforating artery in surgery in the region of the base of the brain such as that for basilar artery aneurysm. PMID- 4024182 TI - Distribution of acidic glycosaminoglycans, lipids and water in normal human cerebral arteries at various ages. AB - Functional alterations in arterial acidic glycosaminoglycans (AGAG) may be related to the pathogenesis of some forms of cerebrovascular disease. We measured the AGAG, lipid and water content of human cerebral artery of 275 normal males at various ages. These measures were separately carried out in the main trunk and distal branches. The AGAG components were analyzed by an enzymatic assay method employing specific enzymes which digest AGAG to assess topographic change and aging variations. The total AGAG content was higher in the main cerebral artery than in the distal branches. The main AGAG component of the normal main cerebral artery was heparan sulfates (HS), constituting half the total AGAG, followed by moderate amounts of dermatan sulfate (DS), chondroitin-6-sulfate (C-6S) and chondroitin-4-sulfate (C-4S). Hyaluronic acid (HA) was a minor component and it was more prominent in young arteries. Heparin could be occasionally detected. With advancing age, the relative amounts of HS, HA, chondroitin and C-4S both in the main trunk and distal branches decreased but those of DS and C-6S increased. The total lipid, cholesterol ester and triglyceride content was greater in the main trunk than in the distal branches; the total lipid content increased with age. A possible function of the cerebral arterial AGAG is discussed with respect to change in lipid and water content according to topographic sites and aging. PMID- 4024183 TI - Brainstem auditory evoked responses in brainstem infarction. AB - Brainstem auditory evoked responses (BAERs) were recorded in 40 patients with clinically definite brainstem infarction, and results were compared to localizations from physical signs and CT scans. The BAER was abnormal in 92% of patients with evidence on physical examination of dysfunction of lateral structures in the pons or midbrain. Normal BAERs were seen with medially-situated or medullary lesions. When both rostrocaudal level and lateralization were considered, the BAER indicated damage in additional areas not evident on physical examination in 25% of patients. However, physical signs indicated damage in areas not reflected by the BAER in 22% of patients. Therefore, the BAER complements the localization obtained from physical findings. BAERs were abnormal in more of these patients than were CT scans, and thus are useful for confirmation of bedside impressions. PMID- 4024184 TI - 5-hydroxytryptamine: source of activator calcium in human basilar arteries. AB - We performed experiments in human cerebral arteries to determine the source of activator calcium during contractions induced by 5-hydroxytryptamine. Rings of human basilar artery obtained at autopsy were mounted for isometric tension recording in organ baths filled with a physiological salt solution. Contractile responses to 5-hydroxytryptamine were virtually abolished in Ca++-free solution, and inhibited significantly by nimodipine. In both cases, the depression of the response to 5-hydroxytryptamine was comparable to that seen when KCl was used to contract the vessels. These experiments demonstrate that 5-hydroxytryptamine mediates contraction of the smooth muscle in human basilar artery by increasing membrane permeability to extracellular calcium. PMID- 4024186 TI - Stroke-in-progression. AB - Stroke-in-progression or stroke-in-evolution or progressing stroke is a clinical entity which is frequently encountered in several major types of stroke possibly even more frequently than the classical abruptly completed stroke. Stroke-in evolution is in fact a mosaic or constellation of conditions including various causes (large infarcts, lacunes, distal fields infarcts, hemorrhages), various types of evolution and various pathophysiological mechanisms. The number of well studied clinical cases in the literature is surprisingly small. Many of the proposed definitions are not adequate. Although it has been advised that the concept of of progressing stroke be discarded, this advice seems premature considering that it is a common and critical condition and one which has been in fact imperfectly and incompletely investigated. Instead, it would appear better to organize a prospective study with detailed clinical reports, serial CT, angiography, and when possible NMR PET or SPECT and detailed pathological examination of brain and extra-intracranial cerebral arteries. The magnitude of the task is such that a multicenter study would probably be required. PMID- 4024185 TI - Chronic ocular ischemia and carotid vascular disease. AB - Venous stasis retinopathy and ischemic oculopathy are ocular manifestations of ischemia in the distribution of the carotid artery. While not as common as transient monocular blindness or retinal arterial emboli, they are readily recognizable and indicate the presence of severe, often bilateral, carotid occlusive disease. Patterns of occlusion vary but usually include complete occlusion of at least one common or internal carotid artery, often accompanied by occlusion or narrowing in the opposite carotid system. The ocular findings in venous stasis retinopathy and ischemic oculopathy indicate ongoing ocular ischemia and may progress to intractable neovascular glaucoma. Therapy, individualized for the specific pattern of occlusive changes, may be directed toward prevention of stroke or may be indicated primarily for the reversal of ocular ischemia and prevention of blindness secondary to neovascular glaucoma. PMID- 4024188 TI - Should lumbar puncture be part of the routine evaluation of patients with cerebral ischemia? PMID- 4024187 TI - Intracerebral haemorrhage and angiographic beading following ingestion of catecholaminergics. AB - We report two cases of serious intracerebral haemorrhage occurring in young women following their first use of oral medications containing catecholaminergic agents (phenylpropanolamine in combination with ephedrine or pseudoephedrine). Both women were previously well, and there was no evidence for systemic vasculitis, coagulopathy, aneurysm or arteriovenous malformation. Angiography in both cases, performed approximately forty hours following drug ingestion, revealed the beading pattern typical of that seen in previously reported cases of presumed amphetamine-induced "vasculitis." We believe that this arteriographic abnormality is non-specific and should not be construed as necessarily indicative of arteritis. PMID- 4024189 TI - Ataxic-hemiparesis. PMID- 4024190 TI - The natural history of carotid arterial disease in asymptomatic patients with cervical bruits. PMID- 4024191 TI - [Current problems in the participation of forensic physicians in solving public health tasks]. PMID- 4024192 TI - [Tasks of improving forensic medical expertise in presenting material evidence]. PMID- 4024193 TI - [Status of and means for improving expertise in disputed paternity]. PMID- 4024194 TI - [Isoenzyme polymorphism and its importance for forensic medical expertise in presenting material evidence]. PMID- 4024195 TI - [Forensic medical significance of pathological changes in the hair]. PMID- 4024196 TI - [Significance of the hydrodynamic factor in the mechanism of the formation of injuries in blunt trauma]. PMID- 4024197 TI - [Determination of the sequence of pelvic bone fractures in repeated blunt trauma]. PMID- 4024198 TI - [New morphological sign of a gunshot exit wound]. PMID- 4024199 TI - [Metabolism of 1,2-dichloroethane in the human body in acute poisonings]. PMID- 4024200 TI - [Use of the emission spectrographic method in diagnosing fatal poisonings by the death cup]. PMID- 4024201 TI - [Determination of isolanid in cadaveric material]. PMID- 4024202 TI - [Determination of the degree of alcoholic intoxication by laboratory studies in different stages of alcoholism]. PMID- 4024203 TI - [Attachment for infrared photography]. PMID- 4024204 TI - [Establishing the mechanism of automobile injury]. PMID- 4024205 TI - [Expertise on a gunshot wound in the case of fragmentation of the small-caliber bullet]. PMID- 4024206 TI - [Death from a puncture wound of the femoral vein from the end of a slab during a fall]. PMID- 4024207 TI - [Pearl tumor and telangiectasia of the hypophysis as a cause of sudden death]. PMID- 4024208 TI - Cyclosporine quality control program is a reality. PMID- 4024209 TI - Theophylline serum concentrations in ambulatory patients with chronic obstructive pulmonary disease. AB - A two-part study was designed to investigate the application of theophylline serum concentration data at a Veterans Administration Medical Center. The investigation was unique in its use of ambulatory patients instead of hospitalized patients as study subjects for assessing the use of laboratory tests. As has been found in other studies that examined different drugs and involved hospitalized subjects, this investigation discovered significant problems in the ordering, application, and documentation of these data when judged against established criteria. There was no significant difference in the appropriate use of these drugs between physicians specializing in pulmonary versus general medicine. Of clinical importance also are the findings that confirm a positive correlation between the proper use of these tests and improvement in patient outcome, and the demonstrated relationships between clinical symptoms and subtherapeutic and toxic serum concentrations of theophylline. PMID- 4024210 TI - Bayesian pharmacokinetic/pharmacodynamic forecasting of prothrombin response to warfarin therapy: preliminary evaluation. AB - The ability of a pharmacokinetic/pharmacodynamic Bayesian forecasting computer program to predict prothrombin response to warfarin therapy was investigated. The performance of the program was evaluated retrospectively in an inpatient study population of 45 subjects. Predictions of prothrombin response at discharge, based on zero to five serially measured prothrombin ratios, were compared. Precision of prediction was measured by root mean squared error (rmse), bias was measured by average prediction error, and significance (p less than 0.05) was determined by 95% confidence intervals and correlation coefficients. Eleven (3.8%) predictions exceeded established limitations of the pharmacokinetic/pharmacodynamic model and were excluded from data analysis. Correlations between measured and predicted prothrombin ratios for all methods were significant. The five prothrombin ratio feedbacks provided the most accurate predictions (rmse 0.219). These predictions were significantly better than the population parameter (rmse 0.418), one (rmse 0.401), and two (rmse 0.459) prothrombin ratio feedback predictions. The predictions based on population parameters and one prothrombin ratio feedback were significantly biased. When provided with sufficient feedback, the bias was not apparent and the predictive performance improved with each additional prothrombin ratio. The predictive performance of the four and five prothrombin ratio feedbacks is sufficient to provide clinically useful dosage guidelines early in the course of warfarin therapy. The population parameter estimates require further delineation in order to improve the performance of limited prothrombin ratio feedback predictions. PMID- 4024211 TI - Influence of high-dose pentobarbital on theophylline pharmacokinetics: a case report. AB - The effect of high dose pentobarbital coma therapy on the total body clearance of theophylline (CLT) was evaluated in a neurosurgical patient. Preinduction and induction CLT were 4.22 and 8.02 L/h, respectively, which represented a 95% increase in the CLT as a consequence of pentobarbital therapy. Although barbiturates have been shown to induce hepatic microsomal enzymes, previous reports minimize their effect on CLT in humans. This case report demonstrates remarkable alterations in the CLT as a result of high doses of pentobarbital, necessitating the need for substantial dosage adjustments of theophylline. PMID- 4024212 TI - Red blood cell electrolytes for monitoring digoxin therapy in adults. AB - Red blood cell (RBC) electrolyte concentrations were determined, with a method that can be applied easily in any clinical chemistry laboratory, in 18 patients not on digoxin therapy and 37 patients on maintenance digoxin therapy for various diagnoses. Of the digoxin-treated patients, 11 had electrocardiographic changes and other clinical evidence of digoxin toxicity. Mean RBC sodium was higher and mean RBC potassium was lower in patients on prolonged digoxin therapy than in controls, and these changes were more pronounced in patients with toxic symptoms. In the group of 11 patients with toxicity, a positive correlation was found between the ratio of RBC sodium to potassium and plasma digoxin levels (r = 0.8234, p less than 0.05). Plasma digoxin concentrations did not clearly distinguish between toxic and nontoxic patients. The RBC sodium/potassium ratio, however, identified 35 of 37 patients correctly, with two patients from the toxic and two patients from the nontoxic group giving the same results. Changes in intracellular erythrocyte electrolytes in adults appear to correlate closely with clinical signs of digoxin toxicity. PMID- 4024213 TI - Influence of body fat on the volume of distribution of theophylline. AB - Twenty-six acutely bronchospastic patients admitted to the emergency room of an acute care hospital were studied to determine the influence of body fat on the volume of distribution (Vd) of theophylline. Total body weight (TBW), height, skinfold thickness (at three sites), and theophylline levels around an intravenous aminophylline dose were measured. Ideal body weight (IBW), percentage of body fat, and absolute and relative Vd of theophylline were calculated. Vd of theophylline correlated better with IBW than TBW. No relationship was identified between Vd normalized to IBW and either percentage of body fat or the ratio of TBW to IBW. This indicates that in our sample (0.8 IBW less than TBW less than 1.4 IBW), distribution of theophylline into adipose tissue was not an important determinant of Vd. Theophylline's Vd was best estimated by the formula Vd (L) = 0.419(L/kg) X IBW(kg). PMID- 4024214 TI - Falsely elevated digoxin concentrations in patients with liver disease. AB - Immunoreactive digoxin was determined in blood samples of 73 patients with liver disease who did not take any cardiac glycoside. Seventeen of these patients reproducibly showed false-positive results, as much as 3.6 ng/ml. Patients with concomitant renal disease had higher assay results (mean 1.9 n/ml) than patients with normal renal function (mean 0.6 ng/ml). It is concluded that blood of a number of patients with liver disease of different causes contains a substance that interferes with digoxin radioimmunoassay. PMID- 4024215 TI - Determination of chloroquine and its desethyl metabolite in whole blood: an application for samples collected in capillary tubes and dried on filter paper. AB - A high performance liquid chromatography method for analysis of chloroquine and desethylchloroquine was adapted for 75 microliters aliquots of whole blood obtained by finger-prick and dried on filter paper. The precision of the method was satisfactory at whole blood concentrations of 40 nmol/L (coefficient of variation, 5%). The dried samples were stable for at least 7 weeks at 20 degrees C. The concentrations in venous whole blood and in dried samples correlated well. The correlation coefficient was 0.99 for chloroquine and 0.97 for desethylchloroquine. Chloroquine concentrations were marginally but significantly higher in venous whole blood. When fitted to a linear equation (y = bx + a) the relationship was y = 0.96x + 0.03. Desethylchloroquine concentrations did not differ significantly in venous whole blood and in finger-prick blood dried on filter paper. The method is specific and sensitive enough for pharmacokinetic studies and can be used in areas with limited technical facilities. PMID- 4024216 TI - Chloroquine and desethylchloroquine in plasma, serum, and whole blood: problems in assay and handling of samples. AB - A spectrophotofluorometric method for determination of chloroquine in body fluids was compared with a recently developed high performance liquid chromatographic (HPLC) method. The spectrophotofluorometric method was found to codetermine the main metabolite desethylchloroquine and thus to give higher "chloroquine" concentrations than the HPLC method. The concentrations determined with spectrophotofluorometry roughly corresponded to the calculated sum of chloroquine and desethylchloroquine as determined with the HPLC method. The concentrations of chloroquine and desethylchloroquine were higher in serum, and considerably higher in whole blood, than in plasma. The duration and force of centrifugation greatly influenced the concentrations of chloroquine and desethylchloroquine found in plasma. The concentrations decreased as centrifugal force increased reaching relatively stable levels at 500 g. Increasing the centrifugation time partly compensated for lower g forces. These methodological problems can be avoided by using whole blood for determinations of chloroquine. Since the biological activities of desethylchloroquine and chloroquine are not the same, drug monitoring should be performed with a method distinguishing between the parent drug and the metabolite. PMID- 4024217 TI - A sensitive liquid chromatographic assay for plasma aspirin and salicylate concentrations after low doses of aspirin. AB - An original, highly sensitive and specific high performance liquid chromatographic method has been developed for the measurement of aspirin and salicylate in plasma. Minimum concentrations of 10 micrograms/L (aspirin) and 0.5 mg/L (salicylate) can be measured using 1 ml of plasma. After collection, plasma is first treated with physostigmine sulfate to inhibit enzymatic hydrolysis of aspirin to salicylate. Maximal recovery is achieved using an acid extraction into anhydrous diethyl ether with a subsequent drying-down step in an iced water bath. Aspirin and salicylate are separated by elution with a mixture of methanol, 1 butanol, orthophosphoric acid, and water on a reversed-phase octadecyl silane column at 47 degrees C and detected at 234 nm by ultraviolet absorption. Quantitation is achieved using the peak height ratio of aspirin and salicylate to internal standard (m-anisic acid). The assay has been used for the study of simultaneous aspirin and salicylate pharmacokinetics after a single oral dose of 100 mg soluble glycinated aspirin for platelet antiaggregatory therapy in six subjects, one of whom was also studied after receiving a 600 mg dose. PMID- 4024218 TI - Therapeutic monitoring of chlorpromazine I: Pitfalls in plasma analysis. AB - Pooled plasma from healthy volunteers was spiked with pure, synthetic chlorpromazine (CPZ), chlorpromazine sulfoxide (CPZSO), or chlorpromazine N-oxide (CPZNO), and then made alkaline with either sodium hydroxide or sodium carbonate. The samples were allowed to stand at room temperature for various timed intervals before extraction with organic solvent. It was found that CPZNO was reduced to CPZ in plasma made alkaline with sodium hydroxide, but not in protein-free buffer solution at high pH nor in plasma made alkaline with sodium carbonate. The reaction appears to take place through reducing equivalents generated by the action of sodium hydroxide on plasma proteins. Thus, apparent concentrations of CPZ in plasma from patients were elevated by as much as 343% when sodium hydroxide was used compared with concentrations in aliquots of the same plasma samples alkalinized with sodium carbonate. The amount of CPZ produced from CPZNO depends on the type of extraction procedure employed as well as on the quantity of sodium hydroxide added to the plasma. By contrast, no interconversion between CPZ and CPZSO or CPZNO and CPZSO was observed in plasma alkalinized and extracted under any of the conditions tested. PMID- 4024219 TI - Comparative determination of flupentixol in plasma by gas chromatography and radioimmunoassay in schizophrenic patients. AB - A new method of measuring flupentixol in plasma was developed using gas chromatography (GC) with a nitrogen-phosphorus detector. The minimal quantifiable concentration was 0.5 ng/ml and the day-to-day coefficient of variation was 9.4% at 2 ng/ml. A comparison of flupentixol concentrations measured with radioimmunoassay (RIA) and GC was undertaken on 100 plasma samples obtained from 50 schizophrenic patients. The RIA method tended to overestimate flupentixol concentrations compared with GC. The reasons for this discrepancy might be the presence in plasma of the inactive trans(E)-flupentixol isomer and metabolites of flupentixol, which would cross-react with the antibody. The results of this study show that GC can be used for therapeutic monitoring of flupentixol. PMID- 4024220 TI - Desmethylimipramine overdose: nonlinear kinetics in a slow hydroxylator. AB - A case of desmethylimipramine (DMI) overdose is described. The analysis of DMI and its main metabolite, 2-hydroxydesmethylimipramine (2-OH-DMI), in plasma was performed by high performance liquid chromatography with fluorescence detection. Characterization of the elimination kinetics of DMI by using the SAAM 25 computer program indicated Michaelis-Menten kinetics. The patient was phenotyped with respect to debrisoquine hydroxylation and classified as a slow hydroxylator. Both nonlinear kinetics and slow hydroxylation might have contributed to the marked difference between the concentration of DMI and 2-OH-DMI in plasma in this patient. PMID- 4024221 TI - Analysis of tricyclic antidepressants in serum and plasma yields similar results. PMID- 4024222 TI - [Research on the aged within the framework of social geography]. AB - Until now social gerontological research in the Netherlands has primarily been done by psychologists and sociologists. Geographic contributions are subordinate. Nevertheless there are innumerable geographical aspects which influence ageing and human behaviour of the elderly. Several studies on ageing have already been made, considering geographical topics as distribution, migration, housing, mobility and accessibility of provisions. The geographer can supply enhanced contributions in the future. PMID- 4024223 TI - [Problems of aging in China]. AB - A WHO consultancy to the 'National Seminar on Geriatrics' in Beijing provided an opportunity to get some ideas about the problems of ageing in China. Since 1949 life expectancy has doubled and it has been estimated that between now and the end of the century the 65+ group will double to a total of approximately 100 million people. This will be the fastest growing ageing population in history. With more than 1000 million inhabitants China is the largest country in the world and also because of epidemiological facilities it offers unique opportunities to study for instance maximum life-span. Results sofar support the view that this will not exceed the generally accepted figure of 120 years. Institutional care is limited, but this is at least partly offset by the structure of society, having the family as the central unit. Preventive medicine scores high and one should hope that it will contribute to geriatrics, as it has contributed to other parts of medicine. PMID- 4024224 TI - [Drug utilization in 3 nursing homes for somatic patients]. AB - An investigation was carried out of the drug-use of 198 patients in three nursing homes. Almost 80% of the patients used 2 to 7 drugs. The average number of drugs per patient relating to regular medications for internal use was 4,36. It was 5,25 when p.r.n. medications and medications for external use were also included. The most frequently used drugs were psychotropics, analgetics, cardiac drugs, diuretics and laxatives. Combinations of drugs (including alcohol) that can lead to interaction, were often prescribed. The following combinations were found to have the highest frequency: two drugs with anticholinergic action, digoxin with a potassium-loosing diuretic, two or more drugs which can cause hypotension. The number of patients with one or more of these combinations as well as the number of combinations per patient increased in correspondence with drug-use per patient. PMID- 4024225 TI - [Control of allocation through decision making on requests for care. Study of indications for nursing homes]. AB - The allocation of social services is the central theme in this article. More in particular attention is drawn to the admission-decisions for residential homes. The Dutch government has created specific regulatory forms to control the admission policy of private institutions in this field. Two interrelated goals are associated with this regulation: first that of selectivity (admission restricted to those 'in need'), and second that of objectivity (equal treatment and equal opportunities with regard to admission). This article gives the results of an empirical investigation into the problem of goal-attainment. It is concluded, that both selectivity and objectivity are only partially achieved. These findings will be relevant for intended changes in admission-policy. Current proposals present the choice between more or less centrally guided admission norms, favoring the latter. However, from the theory of rationing this can be seen as a shift towards a more hidden system of rationing, which is less predictable in outcome contrary to the aforementioned goals of selectivity and objectivity. PMID- 4024226 TI - Blood banking in the United States--1981. AB - Combined data from the American Association of Blood Banks, American National Red Cross, and Community Council of Blood Centers for 1981 compared to similar data for 1980 show an increase in the collection and use of blood and components. In 1981, a greater percent of donor units was converted to multiple components. Use of blood resources was more efficient in 1981 than in 1980. PMID- 4024227 TI - Acquired immune deficiency syndrome in the Middle East from imported blood. AB - In Saudi Arabia, a native patient with no known risk factors for the acquired immune deficiency syndrome (AIDS) developed both clinical and laboratory evidence of AIDS 2 years after receiving transfusion of 11 units of blood obtained from a commercial distributor in the United States. This case suggests that a history of transfusions of blood components imported from areas where AIDS is prevalent should be elicited from patients in the Middle East with symptoms and physical findings suggesting AIDS. PMID- 4024228 TI - Development of an optimized additive solution containing ascorbate-2-phosphate for the preservation of red cells with retention of 2,3 diphosphoglycerate. AB - An additive solution containing adenine, ascorbate-2-phosphate, sodium phosphate, dextrose, and saline was developed for packed red cell preservation. The combination of all components was simultaneously optimized so that the resulting solution produced the maximum retention of both red cell adenosine triphosphate (ATP) and 2,3 diphosphoglycerate (2,3 DPG) concentrations. Fourteen nutrient combinations were tested; each combination was evaluated for 42 days of storage using cells from three donors. The nutrient combinations were chosen with the aid of a computerized experimental design process. Results of the experiments were modeled by regression analysis, and the model was optimized to produce the "best" formulation for simultaneous maintenance of ATP and 2,3 DPG. The resulting mathematically optimal formulation was tested in the laboratory using 10 units of red cells. With this solution, it was possible to store red cells for 42 days with retention of 45 to 55 percent of the initial ATP and 85 to 150 percent of the initial 2,3 DPG. Red cell lysis was low (0.8 percent), and most of the cells were biconcave discs (by scanning electron microscopy) at the end of storage. The studies were carried out in an efficient manner by using computer-optimized experimental design techniques coupled with multiple regression modeling and subsequent computer optimization of the models. This experimental approach has potential application to many current blood banking procedures. This additive solution should maintain viable red cells for 42 days. In addition, the solution will maintain red cell 2,3 DPG throughout storage. PMID- 4024229 TI - Preparation of blood components with saline-adenine-glucose-phosphate-maltose quadruple-pack system. AB - A saline-adenine-glucose-phosphate-maltose (SAGP-maltose) quadruple-pack system was devised to improve the conventional method of preparing blood components. One of the features of this method is that high-speed centrifugation was used as the initial spin in the two-step centrifugation of whole blood. This feature permitted the removal of the buffy coat from red cells at the same time the platelets were isolated. Since the platelets were concentrated without forming a button, the damage to the platelets due to mechanical stress in preparation was minimized. Another major feature was the use of the SAGP-maltose solution. Maltose effectively prevented hemolysis during storage in a protein-poor medium for preserving red cells. Judging from the red cell adenosine triphosphate level and morphology score, it should be possible to store red cells for 35 to 42 days in SAGP-maltose preservative. In addition, approximately 25 percent more plasma was collected in the present system than in conventional multiple-pack systems. PMID- 4024230 TI - Comparison of plateletapheresis with two continuous-flow cell separators using identical donors. AB - Each of 20 donors underwent plateletapheresis on both the CS-3000 (Fenwal) and the 2997 (IBM) blood cell separators. The same operator performed both procedures and conducted all product studies for each donor. Platelet collection efficiency was significantly greater with the 2997 (81%) than the CS-3000 (60%) (p less than .0005). Both techniques provided high platelet yields that were not significantly different (2997: 6.1 X 10(11), CS-3000: 5.7 X 10(11)), permitting comparison of other variables without accounting for different yields. Significantly more leukocytes were present in products collected with the CS-3000 (0.46 X 10(9)) than the 2997 (0.09 X 10(9), p less than 0.0005). More acid-citrate-dextrose was infused during procedures with the 2997 (471 ml) than the CS-3000 (324 ml, p less than 0.0005); the donors' ionized calcium decreased significantly more during procedures with the 2997 (27.3%) than the CS-3000 (17.0%, p less than 0.0005). Hypocalcemic symptoms were more common during procedures with the 2997. Product volume was greater with the 2997 (414 ml) than the CS-3000 (237 ml, p less than 0.0005). All products contained less than 1 ml of red cells. Set-up time was significantly greater with the 2997 (37 minutes) than the CS-3000 (18 minutes, p less than 0.0005), but processing time was significantly less with the 2997 (90 minutes) than the CS-3000 (110 minutes, p less than 0.0005). There was no difference in the decrease in donor platelet count with procedures between the 2997 (27%) and the CS-3000 (26%).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4024231 TI - Factors affecting white cell content in platelet concentrates. AB - In this study, we investigated the factors affecting white cell content in platelet concentrates. White cell yields can be reduced 50 percent by stopping platelet-rich plasma expression when the interface is 1 cm from the top of the blood bag as compared to stopping expression when the interface reaches the top of the bag. Further reductions can be achieved by careful handling during transfer of units from the centrifuge cups to expressors (after the first spin) and by carefully balancing units against each other to ensure proper rotor balance during the first spin. Following these suggestions, blood banks should be able to produce platelet concentrates with white cell yields between 2 and 6 X 10(7) and with platelet yields between 7.5 and 8 X 10(10). Transfusion of this product may reduce febrile reactions and lower the incidence of alloimmunizations. PMID- 4024232 TI - The effect of citrate, calcium, and magnesium ions on the potassium movement across the human platelet membrane. AB - The intracellular K+ concentration in platelets is reduced during storage in citrated plasma. As shown previously, pH has a marked influence on this reduction. The effect of citrate and Ca2+ and Mg2+ on the K+ permeability of the membrane and on the active K+ transport across the membrane was investigated. Platelets were incubated in dialyzed plasma at 37 degrees C, pH 5.5 to 7.9, with and without added Ca2+ and Mg2+ and citrate. After 60- to 120-minute incubation, a steady state was reached, and ouabain was added to inhibit the active K+ transport. In the pH interval 5.5 to 6.2 citrate, Ca2+ and Mg2+ had no influence on either the active K+ transport or the K+ permeability. Between pH 7.1 and 7.9, Ca2+ and Mg2+ decreased the permeability, whereas citrate increased it. At pH 7.9, citrate had a depressing effect on the active transport. These results indicate that a low citrate concentration and a pH below 7 are important for maintaining a high intracellular K+ of platelets during storage in plasma. PMID- 4024233 TI - Modified fluid gelatin. An alternative macromolecular agent for centrifugal leukapheresis. AB - We studied a French modified fluid gelatin (MFG), substituting it for hydroxyethyl starch (HES) in leukapheresis procedures using three currently available blood cell separators, and observing its effects on the function of platelets and granulocytes. As a cell-collecting agent, we found MFG to be as effective as HES with intermittent flow centrifugation (Haemonetics), and slightly less so with one continuous flow device (IBM 2997). MFG was clearly less effective than HES with the Fenwal CS-3000 continuous flow separator, although we have reason to believe it would be possible to improve efficiency with this machine by changing the operating variables. Tests of platelet and granulocyte function showed negligible alteration with either agent and no difference between them. MFG disappears much more rapidly from the circulation than HES (after a single injection, it is undetectable by the third day). Reaction frequency with MFG was about the same as that of HES, with perhaps somewhat more frequent allergic manifestations. PMID- 4024234 TI - "New" autoantibody specificity in autoimmune hemolytic anemia defined with red cells treated with 2-aminoethylisothiouronium bromide and a dithiothreitol-papain solution. AB - Specificity of IgG autoantibodies that react with random red cell samples but not with cells treated with 2-aminoethylisothiouronium bromide (AET)-previously was related to the Kell blood group system. We now describe an IgG autoantibody, from a patient who died with autoimmune hemolytic anemia, that reacted with random red cell samples, Ko cells, and with cells treated with a dithiothreitol-papain solution, but did not react with AET-treated cells or with Rhnull cells. Serological reactivity of the autoantibody is unlike that of IgG autoantibodies that do not react only with Rhnull cells. It appears that the reactive antigen is not part of the Kell or Rh systems, but is probably modified by the membrane anomaly present in Rhnull red cells. PMID- 4024235 TI - Autoimmune hemolytic anemia with concurrence of warm and cold red cell autoantibodies and a warm hemolysin. AB - This report describes the laboratory findings and clinical course of a patient with thrombophlebitis, venous gangrene, and autoimmune hemolytic anemia. Three concomitant red cell autoantibody activities were detected: a low-titer, high thermal-amplitude, IgM anti-I cold agglutinin; an IgG warm 'incomplete' panagglutinating autoantibody; and an IgM warm hemolysin. PMID- 4024236 TI - Anti-Tcb, an antibody that defines a red cell antigen antithetical to Tca. AB - A patient's serum, used as a source of anti-Goa typing serum, was found to contain a second antibody that detected a 'new' red cell antigen present in approximately 5 percent of blacks, but not yet found in Caucasians. Among blacks, the 'new' antigen shows an antithetical relationship to the high frequency antigen Tca, as evidenced by tests on eight unrelated Tc(a-) black women and the families of two of these propositi. The antigen, designated Tcb, has not been found on the red cells of Tc(a-) persons whose racial origins differ from the propositi of this report, which suggests that more than one genetic mechanism can produce the Tc(a-) phenotype. The presence of both anti-Goa and anti-Tcb in the same serum appears to be a coincidental and unrelated finding. PMID- 4024237 TI - A clinically significant anti-N in a patient whose red cells were negative for N and U antigens. AB - A patient with sickle cell anemia had M+N-S-s-U-phenotype and developed anti-E, anti-U, and anti-N after multiple transfusions. The anti-N was IgG, showed positive red cell mononuclear phagocyte assay, caused shortened survival of 51Cr labeled N+ red cells, and incited a delayed hemolytic transfusion reaction. The anti-U also caused decreased survival of U+ cells. The serological findings indicated that the anti-N recognized both N and 'N' antigens. PMID- 4024238 TI - Management of patients with anti-Cartwright (Yta). AB - Five patients with anti-Cartwright (Yta) in their serum were observed during a 14 month period. One of the patients in whom a 51Cr-labeled donor red cell survival study was done showed increased destruction of infused Yta-positive red cells while three other patients tested showed a survival of greater than 85 percent at 1 hour. None of the antibodies potentiated interaction between sensitized red cells and heterologous activated mononuclear cells. The fifth patient received many transfusions of Yta-positive red cells without any adverse reaction. Performance of a 1-hour red cell survival with 51Cr-labeled Yta-positive cells is recommended when time permits to determine whether patients with anti-Yta can receive Yta-positive red cells or, alternatively, whether they must receive Yta negative red cells. This approach not only is the safest for the patient, but allows conservation of Yta-negative blood. Such an approach also should be used in patients with antibodies against other high-incidence antigens. PMID- 4024239 TI - The predictive value of crossmatching platelet transfusion for alloimmunized patients. AB - To determine the predictive value of a radiolabeled antiglobulin test for platelet crossmatching to select platelets for transfusion, we evaluated 230 transfusions in 42 alloimmunized oncology patients. Transfusions were classified according to the degree of HLA match. The value of the crossmatch in predicting platelet transfusion outcome was analyzed for each HLA category. For predicting the 1-hour corrected platelet count increment of all transfusions, the sensitivity of the test was 86 percent, specificity 84 percent, and total predictive value 84 percent. The crossmatch technique had similar predictive ability in all categories of HLA match, whether analyzing the results on the basis of the 1- or 24-hour platelet count rise. PMID- 4024240 TI - Treatment of hyperkalemia with exchange transfusion. AB - Exchange transfusions using whole blood less than 24 hours old and deglycerolized red cells reconstituted with fresh-frozen plasma were performed in two premature infants for the treatment of hyperkalemia and cardiac arrhythmia. Improvement of their condition was immediate. PMID- 4024241 TI - Perioperative blood transfusion in patients with colon carcinoma. AB - The effect of perioperative blood transfusion on 5- and 10-year survival following curative resection for intra-abdominal colon carcinoma was investigated retrospectively. Two hundred and seven patients with Dukes' stages A, B, and C carcinoma were divided into two groups: those who received perioperative blood transfusion and those who did not. The data indicated that survival was not altered by blood transfusion during primary surgical tumor resection. Location of tumor in intra-abdominal colon, size of tumor, units of blood received, and stage of disease also were considered in our analysis but did not change this conclusion. PMID- 4024242 TI - Mitral valve prolapse. PMID- 4024243 TI - Increase in urinary thromboxane B2 in rats caused by cyclosporine. PMID- 4024244 TI - Very high concentration in intestinal lymph after oral, but not after intravenous, cyclosporine in the rat. PMID- 4024245 TI - The effect of cyclosporine on organ blood flow. PMID- 4024246 TI - Detection of anti-HLA and antimonocyte antibodies by a chemoluminescence assay. PMID- 4024247 TI - Proceedings of an International Symposium on Cyclosporine-Associated Renal Injury. March 11-13, 1985, San Juan, Puerto Rico. PMID- 4024248 TI - The effect of cyclosporine of renal function in newly diagnosed diabetics. PMID- 4024249 TI - Aetiology and pathogenesis of tropical sprue: do viruses play a role? PMID- 4024251 TI - Relationship of urinary pepsinogen with serum pepsinogen in duodenal ulcer. PMID- 4024250 TI - Nimbidin in duodenal ulcer. PMID- 4024252 TI - [Use of a culture of human peripheral blood lymphocytes for determining the mutagenic activity of urine]. AB - The present study shows that the culture of human peripheral lymphocytes may be used as target cells for detecting the whole urine mutagenic activity. It is established that urine from healthy control cigarette smokers and from non smoking greenhouse workers contacting with a complex of different pesticides significantly increased frequency of chromosome aberrations in the approbated test-system. The data obtained give evidence for the presence of genetically active substances in organisms of the examined individuals. PMID- 4024253 TI - [Role of ethanol tolerance in determining a hereditary disposition to alcoholism]. AB - Genetic-correlative analysis of the tolerance level, amount of alcohol consumed (ml/kg for 1 year) as well as predisposition to the development of alcoholism permitted an assumption on existence of two different genetic factors one of which determined the tolerance level and the other one-predisposition to disease. PMID- 4024254 TI - [Cultivation of chorionic cells in studying the fetal karyotype in the 1st trimester of pregnancy]. AB - Primary culture of chorion cells obtained during the first trimester of pregnancy (7-9 weeks) through artificial abortion or by transcervical biopsy of the chorion tissue is an object for cytogenetic examination of fetus cells. The application of this cell culture for prenatal diagnosis of human hereditary diseases has a considerable advantage in time as compared with a routine method of using amniotic fluid cell culture during the second trimester of pregnancy. PMID- 4024255 TI - [Ultrastructure of hematopoietic and stromal cells of the subendosteal region of the bone marrow]. AB - Using electron microscopic cytochemistry and immunoelectron microscopy, the ultrastructure of bone marrow (BM) cells of the subendosteal region with a high colony-forming (CFUs) ability was studied. In comparison with the central part of BM, the subendosteal region of CBA and BALB/c mice contains a higher number of lymphocyte-like mononuclears, bearing an antigen, common with the brain surface one but negative for peroxidase and acid and alkaline phosphatase. The ultrastructure of these cells is similar to that of presumptive hematopoietic stem cells. In the subendosteal region mononuclears are concentrated with the lower nucleo-cytoplasmic ratio, a feston-like line of the nucleus and more numerous organoids. These cells are characteristic of BM myeloid islands composed of granulocytes being on various stages of differentiation, and of reticular cells positive for alkaline phosphatase. PMID- 4024256 TI - [Ultrastructural changes in the muscle fibers of the rat diaphragm and the dynamics of intracellular calcium redistribution as affected by an anticholinesterase substance--chlorophos]. AB - Ultrastructural changes of the rat diaphragm muscle fibers and electron histochemical distribution of calcium ions were studied following chlorophos administration in 5, 15 and 45 minutes (dose - 300 mg/kg, intraperitoneally). The local swelling of mitochondrial matrix and the appearance of contractures were found first in postsynaptical region. Then the postsynaptical alterations increased; the swelling and fragmentation of sarcoplasmic reticulum were observed in addition to desorganization of mitochondrial ultrastructure. Granules of the histochemical product were revealed in mitochondria, in the sarcoplasmic reticulum and in filaments. Changes in distribution of calcium ions in the rat diaphragm muscle fibres after chlorophos administration and the role of Ca++ the in the mechanism of muscle alteration discussed. PMID- 4024257 TI - [Electron microscopic-cytochemical study of succinate dehydrogenase activity of nerve tissue cells of human embryos in vitro]. AB - The ultrastructural localization of succinate dehydrogenase (SDH) activity was revealed in astrocyte-like cells of 26 days old nervous tissue organotypic cultures. The Kerpel-Fronius and Hajos (1968) technique was employed using potassium ferricyanide as an artificial acceptor of electrons. The localization of the reaction product was seen more often in cells with long, thread-like mitochondria. The appearance of such organelles with a large membrane length and high enzymatic activity is suggested to reflect one of the mechanisms of adaptation of nervous tissue cells providing the adequate level of the energy supply under in vitro conditions. PMID- 4024258 TI - [Differentiation pathways of primary erythroid cells in chickens]. AB - Proliferation and differentiation processes of chick embryo primary erythroid cells (PEC) were studied. A novel differentiation pathway was discovered by which cells of proerythroblastic and erythroblastic stages are blocked in G1 or G2 phases, to develop then directly into reticulocytes, i.e. terminally differentiated non-dividing cells with high hemoglobin contents differing in shape from erythrocytes. These cells appear in blood two days earlier than erythrocytes, then they co-exist with the latter and are eliminated in parallel with them. This pathway leads to a rapid enrichment of PEC with hemoglobin. A fraction of PEC forms accessory nuclei, which, as it is shown here, contain an extra quantity of DNA. Compared to the diploid ones, such cells reveal increased hemoglobin contents which enabled us to assume that they may have amplified the globin genes. The above-mentioned pecularities of cytodifferentiation may be presumably an adaptation to oxygen supply of growing embryos which are known to stay in hypoxia. A comparison of these results with results of our earlier study on experimental anemia makes it possible to suppose that pecularities of these two types of cytodifferentiation may be based on similar or, perhaps, analogous mechanisms of regulation. PMID- 4024259 TI - [DNA synthesis and content and the accumulation of total protein and hemoglobin during the differentiation of primary erythroid cells in chickens]. AB - Using cytophotometric and autoradiographic methods, it was shown that on days 2-3 of embryogenesis primary erythroid cells (PEC) divided actively. The distribution of erythroblasts (EB) according to their DNA content is not, however, typical of a proliferating population: it contains an unusually large number of 4c cells resulting from the cell cycle arrest at the G2 phase. It is established that reticulocytes (RC) do not divide and are arrested at G1 or G2 phases, since they do not incorporate 3H-thymidine after their formation is complete and their DNA contents are strictly confined to either 2c or 4c. All types of PEC include a large number of cells containing H2c DNA which is due either to the cell cycle arrest at the S phase, or to the formation of accessory nuclei. All PECs have much higher contents of hemoglobin and total protein than do adult hen erythrocytes (EC). Hemoglobin and total protein contents of H2c and accessory nuclei containing cells are much higher than those in 2c-cells. We have calculated that adult birds and embryos contain the same amount of hemoglobin per gram of weight, but the quantity of red blood cells in the former is ten times higher. A conclusion is drawn that proliferation and cytodifferentiation regulation mechanisms are directed, in primary erythropoiesis, to intense hemoglobinization of the cells, and, in adult erythropoiesis, to increasing their number. In both the cases homeostatic regulation of erythropoiesis works.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4024260 TI - [Changes in the activity of hydrogen ions in lymphocytes during the endocytosis of concanavalin A]. AB - Changes of hydrogen ions activity in rat thymocytes were studied during the process of concanavalin A (Con A) endocytosis by cells. A possibility was shown to use fluoresceinisothiocyanate-labeled Con A for measuring pH values in the sites of mitogen localization. It is established that during the action of Con A endocytotic vesicles with low pH value are formed, while the pH value of the cytoplasm is increased. The pH value measured in the sites of mitogen localization depends on the treatment of cells by alpha-methyl-D-mannoside and sodium azide. Mechanisms of acidic-basic equilibrium changes in the cytoplasm of lymphocytes upon cell stimulation with mitogens are discussed. PMID- 4024261 TI - [Cell cycle parameters and proliferative activity in chorioallantois tissues at various stages in chick embryo development]. AB - Two peculiarities of cell population kinetics are characteristic of the provisional tissues of the chick embryo chorioallantois. The one is that the proliferative pool is relatively small at relatively early stages of embryogenesis (8 day incubation). The other is that at the final stages of embryogenesis, when proliferative activity in the embryo cell populations is still high, the cell reproduction is practically stopped. The process of tissue differentiation in chorioallantois, on the one hand, is accompanied with a withdrawal of a considerable part of cells from the cycle of reproduction, but on the other hand this differentiation affects the cells that have remained in the proliferative compartment which is reflected in modifications of either the cell cycle structure or the cell population composition. PMID- 4024262 TI - Tick survey on goats and sheep in Kenya. AB - A tick survey was done on sheep and goats in Siaya and Kakamega Districts, Kenya between October 1980 and October 1981. Most of the animals were found to carry one to 10 ticks with no significant difference between sheep and goats. The most abundant species was R. appendiculatus followed by R. evertsi. There were more male than female ticks found on the animals. Thirty per cent of the farms visited practised the hand picking method of tick control while 14% regularly dipped their animals. PMID- 4024263 TI - Reproductive performance, pre-weaning growth rate and pre-weaning lamb mortality of Djallonke sheep in Ghana. AB - Production records for a flock of Djallonke sheep kept in the forest belt of Ghana were analysed to determine the effects of some environmental factors on the performance of the breed. The period under study covered April 1969 to November 1979. The mean ages at first conception and first lambing and the mean lambing interval were 498, 638 and 264 days respectively. The overall twinning rate and prolificacy were 30.7 and 130.6% respectively. The season of birth and age of dam had significant (P less than 0.05) effects on prolificacy and twinning rate. The birth weights of the lambs were affected significantly (P less than 0.05) by age of dam, type of birth, sex and season of birth with the mean birth weight being 1.77 kg. Weaning weight (mean of 8.36 kg) and pre-weaning growth rate (mean of 0.076 kg/day) were affected significantly (P less than 0.05) by types of birth. Type of birth significantly (P less than 0.05) affected pre-weaning mortality of lambs (overall mean of 20.95%). PMID- 4024264 TI - Preliminary studies on the performance and productivity indices of N'Dama and west African shorthorn cattle in Ghana. AB - The performance of N'Dama and West African Shorthorn cattle in the humid forest zone of Ghana was evaluated using records (1969-1979) on these breeds kept at the UST livestock farm. The mean age at first calving for N'Dama was 32.07 months. Calving intervals of 501.92 and 462.83 days were obtained for N'Dama and West African Shorthorn cattle respectively. The secondary sex ratio for N'Dama calves was not significantly different from the expected theoretical value of 50%; that of the West African Shorthorn was, however, significantly different from the expected theoretical value mainly due to the small size of the population. Average birth weight for the two breeds was not significantly affected by breed, season of birth, weight and age of dam. Sex significantly affected the birth weight of the N'Dama calves. Pre-weaning and post-weaning growth rates of N'Dama male calves were significantly greater than the pre-weaning and post-weaning growth rates of females. For the West African Shorthorn sex did not significantly (P greater than 0.05) affect these traits. Calf mortalities for the two breeds were 10.53% for N'Dama and 21.05% for the West African Shorthorn. Calving percentage was not affected by breed. The productivity indices per cow per year were 72.7 kg for N'Dama and 32.1 kg for the West African Shorthorn. The productivity indices per 100 kg cow maintained per year were 36.8 kg for N'Dama and 16.6 kg for the West African Shorthorn. PMID- 4024265 TI - Trypanosoma evansi infection in buffaloes in north-east Thailand. I. Field investigations. AB - Clinical, parasitological and serological findings of Trypanosoma evansi infections in buffaloes (Bubalis bubalis) from north-eastern Thailand are reported. The overall infection rate was found to be around 20% with a distinct peak of acute infections during the rainy season. The disease is aggravated by normally well tolerated concomitant infections such as liver fluke infestations and by other stress factors. PMID- 4024266 TI - Hyperimmune serum in the control of peste des petits ruminants. AB - The value of administration of hyperimmune serum in the control of peste des petits ruminants was investigated in goats at different stages of the disease. A group of the goats was given hyperimmune serum intravenously at the fever stage of temperature of 40.5 degrees C or above; another group showing no elevation of temperature but with other clinical signs of the disease were also given hyperimmune serum. Results indicated that hyperimmune serum was very effective in reversing the process of the disease if administered at the fever stage but not in animals that had progressed past the fever stage. The goats given the hyperimmune serum survived for 10 days before showing evidence of reinfection. PMID- 4024267 TI - Survey of brucellosis in goats and sheep in the Yemen Arab Republic: comparison of tests for Brucella melitensis infection in sheep. AB - Sera from 538 Yemeni goats and 690 Yemeni sheep were screened for brucellosis by the Rose Bengal Plate Test (RBPT) and reactors confirmed by the complement fixation test (CFT) and the serum agglutination test (SAT). The prevalence among goats was 0.4% and among sheep 0.6%. The prevalence among 183 imported goats and sheep was 4.4%. The sensitivity and specificity of three serological tests available for the diagnosis of brucellosis -CFT, RBPT and SAT - were compared using ovine sera obtained throughout an outbreak of abortion due to Brucella melitensis. The RBPT and the SAT were relatively insensitive compared with the CFT (71 and 44% respectively) and the RBPT was as specific as the SAT when suspicious sera were included. The results suggests that the SAT adds little information when used with other tests and the RBPT has limited applications as a screening test for ovine brucellosis. PMID- 4024268 TI - Activity of the combination of fludalanine and cycloserine against mycobacteria in vitro. AB - The initial steps in the incorporation of alanine into the bacterial cell wall include the conversion of natural to D-alanine by a racemase followed by the coupling of 2 D-alanine molecules by a synthetase to yield a dipeptide. A combination of fludalanine (3-fluoro-2-deutero-D-alanine), an analogue of D alanine that irreversibly inactivates the racemase, and cycloserine, which inhibits the synthetase, has been found to be more active against a wide range of non-mycobacterial organisms than either fludalanine or cycloserine alone. When tested against 16 strains of slowly growing mycobacteria including M. tuberculosis, the combination was no more active than cycloserine alone. However the cycloserine minimal inhibitory concentration (MIC) of the combination against the rapidly growing species M. phlei and M. fortuitum was much lower than the MIC of cycloserine alone, particularly with low ratios of fludalanine to cycloserine, and was within the range attainable by therapeutic cycloserine plasma concentrations in man, suggesting its possible use in the treatment of disease due to M. fortuitum. PMID- 4024269 TI - Prophylactic effect in mice of BCG vaccination against nontuberculous mycobacterial infections. AB - The effect of prior vaccination of mice with Mycobacterium bovis BCG on the subsequent course of acute aerogenic infection with various environmental mycobacteria was tested. A protective effect was recorded against infection with M. avium, and M. kansasii; by contrast no effect was noted against M. simiae or M. intracellulare. The prophylactic effects of BCG were demonstrated regardless of whether vaccination was given by the intravenous or aerogenic routes. These findings support the hypothesis that BCG vaccination, if given prior to contact, can provide some degree of protection against certain non-tuberculous mycobacterial infections. PMID- 4024270 TI - Exogenous reinfection in experimental airborne tuberculosis. AB - This study of experimental airborne tuberculosis in which guinea pigs were infected with tubercle bacilli of low and high virulence, provides no support for hypotheses suggesting that a second or third exposure to tubercle bacilli leads to an adverse effect on host response to the first infecting strain or to the reinfecting strain. The principal influence of the first infection was to protect against a subsequent infection. This protection was most evident as inhibition of the spread of bacilli from the lungs to the spleen. The first infection appeared to exert less influence on events at the site of reimplantation of organisms in the lungs. PMID- 4024271 TI - A clinical evaluation of the diagnostic usefulness of an early dermal reaction to tuberculin: a failure to distinguish between tuberculosis and other respiratory disease. AB - An early (6-8 hour) reaction to RT23 tuberculin which was previously found to distinguish between patients with active tuberculosis and healthy tuberculin positive individuals failed to distinguish between such patients and those with other respiratory diseases. It also failed to distinguish between radiologically active and inactive cases of tuberculosis. Such early reactions were frequent among healthy hospital workers but not among other healthy subjects. PMID- 4024272 TI - The Mantoux reaction in pulmonary tuberculosis. AB - The Mantoux test was done on 181 tuberculous patients, of which 124 were sputum positive. In 102 (93%) sputum positive cases the tuberculin reaction was between 10 and 19 mm. and in only 2 cases was the reaction less than 6 mm. In the sputum negative cases 7 (12%) were Mantoux negative and 5 (9%) had reactions of less than 10 mm. In some of the sputum-negative cases the diagnosis of tuberculosis may have been incorrect. PMID- 4024273 TI - Pleuroscopy in the diagnosis of pleural effusion using a fiberoptic bronchoscope. AB - Forty patients with undiagnosed pleural effusions were investigated by pleuroscopy, using a fiberoptic bronchoscope. Pleural biopsies diagnostic of tuberculosis were obtained in 17 cases, and in 12 of these tubercle bacilli were cultured from the pleural fluid. Pleural biopsy at thoracoscopy is superior to the percutaneous intercostal route and for this purpose the fiberoptic bronchoscope is preferable to the rigid thoracoscope. PMID- 4024274 TI - Disseminated bone and joint tuberculosis 25 years after development of lupus vulgaris. AB - A case of extensive bone and joint tuberculosis is reported in a 62-year-old caucasian woman who had a 25 year history of inadequately treated facial lupus vulgaris. In spite of a good response to standard anti-tuberculosis chemotherapy there was extensive residual joint destruction. PMID- 4024275 TI - Vitamin D 3 metabolism during anti-tuberculosis chemotherapy. PMID- 4024276 TI - Poncet's disease. PMID- 4024277 TI - Tuberculosis of the female genital tract. PMID- 4024278 TI - Effect of medical treatment on intracranial tuberculoma--a CT study. AB - Computerized tomography (CT) provides a non-invasive method for making a reasonably confident diagnosis of intracranial tuberculosis and an opportunity to study the response to treatment. Using this facility a series of 50 patients with intracranial tuberculomas, whose vision or life was not threatened by severe intracranial hypertension, were treated with antituberculosis chemotherapy. Most of the small and medium sized lesions resolved completely. Central liquefaction was observed in one case while only three failed to respond to treatment, there was one death. Three illustrative cases have been reported in detail. PMID- 4024279 TI - Trends in cancer mortality in Italy, 1955-1978. AB - Trends in age-specific and age-standardized cancer death certification rates in Italy from 1955 to 1978 were analyzed. In males total cancer mortality rates increased in all age groups. However, when respiratory and other tobacco-related neoplasms were excluded, death certification rates were roughly stable up to age 64. Moderate decreases in overall cancer mortality have been apparent at younger ages (35-44) since the early 1970's. In females, all the age-specific and the age standardized, under-65 death certification rates decreased; the downward trends were more pronounced (-18.5%) in the younger age group considered (35-44 years). Respiratory cancer mortality increased sharply in males: lung cancer death rates reached a plateau in the early 1970's in the 35-44-year age group, but increased at all subsequent ages. In females, the increase in lung cancer mortality was about 50% in the 45-54 and 55-64-year age groups, but no upward trend was evident in younger women. Other tobacco-related cancers (mouth or pharynx, larynx, esophagus, pancreas, kidney and bladder) also rose considerably. In both sexes, gastric cancer mortality dropped about 50% below age 65, but mortality rates from cancer of the stomach were still considerably higher than in other Western countries. Likewise, mortality from cancer of the (cervix) uteri decreased markedly, mostly in younger age groups. Upward trends in death certification rates were evident for cancers of the bowel (colon and rectum, about 50% in males, and 35% in females below age 65), and of the breast in females. However, these trends have levelled off since the late 1960's, at least in the younger age groups. Certified death rates from cancer of the skin (melanoma) increased over all the periods considered in the young of both sexes. Cancer mortality rates showed marked increases in older (greater than or equal to 65) males, but this can be partially explained in terms of better case ascertainment and more accurate death certification. PMID- 4024280 TI - Inhibition of macromolecular synthesis in P388 mouse leukemia ascites cells by bouvardin (NSC 259968). AB - Bouvardin, a new antineoplastic plant product, inhibits macromolecular synthesis in P388 cells in a dose-dependent manner. At the same concentration of bouvardin, protein synthesis was inhibited to a greater extent than the synthesis of DNA and RNA. There was a reversal of inhibition of both DNA and RNA synthesis after the cells were washed free of bouvardin. However, there was partial reversal of inhibition of protein synthesis when the cells were washed free of the drug. PMID- 4024281 TI - Perfluorocarbone (FDA 20) and extracorporeal circuit of isolated extremity perfusion. AB - The applicability of Fluosol DA 20 as a perfusion fluid was investigated in the isolated limb perfusion of 14 mongrel dogs and its performance compared with that of diluted blood. Control of perfusion parameters permitted a direct comparison of the two perfusion liquids. Muscle tissue, blood and perfusate were analyzed for pH, pO2, pCO2, O2 content, lactate, pyruvate, ATP and creatine phosphate. Due to given experimental conditions, the pH values of the perfusion liquid and muscle tissue were in a slightly acidic range. The oxygen uptake of the perfusion liquids and the oxygenation of tissue was satisfactory, the metabolism of the muscle tissue was not disrupted. PMID- 4024282 TI - Limb-salvage procedure in two patients with spindle cell carcinoma of the lower extremities using isolation perfusion. AB - Two patients with extensive squamous cell carcinoma of the lower extremities, candidate for demolitive surgery, were treated by hyperthermic antiblastic perfusion in extracorporeal circulation. The temperature reached was 41 degrees C and the drug used was methotrexate at the dosage of 500 mg. Radical excision of the ulcer was possible in the 2 patients. Both tumors underwent extensive necrosis, and histology done 1 month after perfusion on surgical specimens showed limited areas of residual malignancy. These 2 patients suggest that hyperthermic antiblastic perfusion may be a limb salvage procedure in the multimodal management of extended squamous cell carcinoma of the extremities. PMID- 4024284 TI - Serum estrogen level in Egyptian breast cancer patients. AB - In menstruating 20-29 year old breast cancer patients, the total estrogen level showed a significant increase in the early follicular phase compared to normal healthy subjects. Such a difference was not observed in 30-45 year-old patients. A nonsignificant decrease was observed in the estradiol level of premenopausal breast cancer patients compared to normal healthy subjects. However, in postmenopausal breast cancer patients, the total estrogen level as well as the estradiol level showed a significant increase compared to that of normal healthy subjects. PMID- 4024283 TI - Role of delayed cutaneous hypersensitivity reaction in classifying patients with bronchial carcinoma. AB - Cell-mediated immune response was evaluated in 150 patients with histologically confirmed bronchopulmonary carcinoma using bacterial and fungal recall antigens injected intradermally (PPD, candida, trichophyton). In the study group negative skin test reaction was found in 51 of 150 patients (34.0%), whereas in the control population it was found in 5 of 33 cases (15.1%) (p less than 0.05). Histologic cell type and stage of disease were defined for each patient. It was possible to calculate the growth rate of the primary tumor only in 68 of 150 patients, and it was recorded as doubling time. Evaluation of the skin test reaction in each prognostic subgroup showed no statistically significant differences. The only statistically significant differences were found when each prognostic subgroup was compared with the control population according to the frequency of a negative response to the skin test, particularly in stage III M1 (p less than 0.05) and stage III M0 (p less than 0.02). The delayed cutaneous hypersensitivity studied with recall antigen stimulation was mainly correlated with the stage of disease, and it should not be considered as an independent prognostic factor. PMID- 4024285 TI - Hodgkin's disease developing in a patient with angioimmunoblastic lymphadenopathy with dysproteinemia--a case report. AB - The case of a woman presenting the clinical and pathologic phenomena of angioimmunoblastic lymphadenopathy (AILD) with dysproteinemia is reported. The patient developed lesions in the lymph nodes, skin, lungs, liver and spleen, and her response to steroid and cyclophosphamide therapy was poor. At autopsy, microscopic findings in the mediastinal and abdominal lymph nodes were consistent with the diagnosis of Hodgkin's disease. Whereas the development of immunoblastic lymphoma is frequent in AILD, Hodgkin's disease is far less common. It is argued that malignant lymphoma in AILD may be the consequence of chronically depressed lymphocyte functions. PMID- 4024286 TI - Leiomyosarcoma of the small bowel. AB - Two cases of leiomyosarcoma of the small bowel are described. Both patients presented a large mass adherent to the intestinal wall, with a central necrotic area communicating with the intestinal lumen. Microscopically, the lesions were identified as grade III leiomyosarcomas. PMID- 4024287 TI - [Lyell's syndrome in a patient treated with allopurinol]. PMID- 4024288 TI - [Cystic dilatation of the choledochus. Apropos of 2 case reports]. PMID- 4024289 TI - [Surgical evaluation of neoplastic bilio-pancreatic icterus: apropos of 55 cases]. PMID- 4024290 TI - [Contribution of echocardiography to the study of the impact of sports on the heart]. PMID- 4024291 TI - [Contribution of echocardiography to the study of the myxedematous heart]. PMID- 4024292 TI - [Iatrogenic strictures of the urethra. Apropos of 67 cases]. PMID- 4024293 TI - [Clinical polymorphism of prostatic adenocarcinoma: apropos of 146 cases]. PMID- 4024294 TI - [Delivery in the malformed uterus. Apropos of 23 cases]. PMID- 4024295 TI - [Management of the newborn infant of the diabetic mother. Apropos of 135 cases]. PMID- 4024296 TI - [Value of determining serum and secretory immunoglobulin A (IgA) in recurrent bronchopulmonary infections]. PMID- 4024297 TI - [Auditory deficiency and language]. PMID- 4024298 TI - [Phytohemagglutinin--a modulator of activity of cytochrome P-450-dependent enzymes of hepatocyte and immunocyte membranes]. AB - The phytohemagglutinin effect in vivo on monooxygenase activity depends on the type of the cells under study (thymocytes, splenocytes, macrophages, hepatocytes) and on the period after lectin injection. Variations of monooxygenase activities associated with different forms of cytochrome P-450 are established to have a number of peculiarities in isolated hepatocytes as compared to those in the liver microsome fraction. These differences are supposed to be due to the effect of nonmicrosomal cytochrome P-450. The results obtained are discussed with regard for phytohemagglutinin effect on systems regulating activity of cytochrome P-450 dependent monooxygenases. PMID- 4024299 TI - [A method of determining the antioxidative activity of biological matter]. AB - A procedure is described for determining antioxidation activity of the water soluble biological material. The procedure is based on the study of kinetics of the reduced 2.6-dichlorophenolindophenol oxidation by air oxygen both with and without the biological material as well as on calculation of the value for the constant of the biological material inhibition of 2.6-dichlorophenolindophenol oxidation as an index of the biological material antioxidation activity. PMID- 4024300 TI - [Chemiluminescent determination of copper in the serum]. AB - A procedure for chemiluminescent determination of copper in the blood serum ash is suggested using an indicator reaction between 4-aminophthalhydrazide and hydrogen peroxide permitting copper to be determined in a minimum (0.003 micrograms) concentrations in 1 ml of the blood serum. PMID- 4024301 TI - [Chemiluminescent determination of iron, copper and cobalt in the serum]. AB - Iron in the presence of diethylenetriamine, an activator, is a catalyst of the chemiluminescent reaction between 4-diethylaminophthalhydraside and hydrogen peroxide. The following conditions are optimal for iron content determination: concentration of 4-diethylaminophthalhydraside - (4-5) X 10(-5) M, H2O2 - 1 X 10( 3) M, diethylenetriamine - 5 X 10(-4) M; pH 10-11. Chemoluminescent reaction between 4-diethylaminophthalhydrazide and hydrogen peroxide is catalyzed also by copper and cobalt ions. This reaction is studied for the possibility to be used to determine iron, copper and cobalt amount in solution without their preliminary separation. A highly sensitive procedure is developed for chemiluminescent determination of these metals concentration in the blood serum with detection limit for iron 1.0, for copper - 0.1 and for cobalt - 0.05 ng/ml. PMID- 4024302 TI - [Effect of freezing-thawing on the adenylate cyclase activity of the rat liver]. AB - Various regimes of freezing and thawing as well as adrenaline and fluoride ions are studied for their effect on the adenylate cyclase activity in liver tissue preparations. The reduction of basal and fluoride-stimulating adenylate cyclase activity and a decrease in the adrenaline-stimulating activity of the enzyme after freezing and thawing are shown. Freezing and thawing are studied for molecular mechanisms of their damaging effect on adenylate cyclase. PMID- 4024303 TI - [Effect of extreme factors and adaptation to high-altitude conditions on peroxidation indices of serum lipids]. AB - High and low temperatures, physical exercises and acute hypoxia are studied for their effect on indices of peroxide lipid oxidation in highly trained persons under alpine conditions (2100-5600 m). Temperature effects (-15 degrees C and +100 degrees C, for 30 minutes) as well as their combination with acute hypoxy cause an increase (by 10-30%) of malonic dialdehyde and a decrease (by 46-70%) of spontaneous chemoluminescence of blood serum in nonadapted people. Adaptation to alpine conditions in combination with physical exercises and low-caloric diet decreases shifts of these indices, considerably increasing the organism stability to the action of such extreme stress agents as high and low temperatures and acute hypoxy. PMID- 4024305 TI - [The Jeune syndrome, asphyxiating thoracic dysplasia. A review and description of 2 siblings]. PMID- 4024304 TI - [Eosinophilic fasciitis. A review and a characteristic case report]. PMID- 4024306 TI - [Giant cell arteritis. Forms of expression and course illustrated by a retrospective study over a 10-year period]. PMID- 4024307 TI - [Ocular side effects of ethambutol (Myambutol). A 5-year Danish review]. PMID- 4024308 TI - [Ectopic pregnancy. A retrospective study over a period of 20 years]. PMID- 4024309 TI - [Preoperative determination of fibrin degradation products (FDP) in the sera of patients with suspected gynecologic tumors]. PMID- 4024310 TI - [Simultaneous occurrence of Trichomonas vaginalis and gonorrhea in women]. PMID- 4024311 TI - [The Miller-Abbott tube introduced endoscopically. Description of a method]. PMID- 4024312 TI - [Accidents on escalators]. PMID- 4024313 TI - [Reversible visual field defects and severe anemia]. PMID- 4024314 TI - [Rhabdomyosarcoma of the urinary bladder]. PMID- 4024315 TI - [Malignant hemangioendothelioma with massive intraperitoneal hemorrhage]. PMID- 4024316 TI - [What is dioxin?]. PMID- 4024317 TI - [Violence against women in their partnerships. III. Education, employment and housing]. PMID- 4024318 TI - [Home examination of 5-week-old infants. Cooperation between doctors and health visitors]. PMID- 4024319 TI - [Acute proctitis]. PMID- 4024320 TI - [The differential diagnosis of infectious proctitis and ulcerative colitis. A prospective study]. PMID- 4024321 TI - [Cardiovascular changes and acid-base balance during bicarbonate and acetate dialysis]. PMID- 4024322 TI - [Review of the transfusion requirements associated with elective surgery]. PMID- 4024323 TI - [Arrhythmias during the first 24 hours of hospitalization for the first episode of acute myocardial infarction]. PMID- 4024324 TI - [Methylprednisolone pulse therapy in Felty's syndrome]. PMID- 4024325 TI - [Urination disorders during Abalgin medication?]. PMID- 4024326 TI - [Systemic anaphylaxis and allergic reactions following administration of penicillins. Report to the Committee of Adverse Drug Reactions]. PMID- 4024327 TI - [Violence against women in their partnerships. IV. Pattern of contact with public institutions]. PMID- 4024328 TI - [The occurrence of benign pulmonary changes in the spouses of previously employed asbestos workers]. PMID- 4024329 TI - [Midges and the nuisance of biting midges]. PMID- 4024330 TI - [Intracranial saccular aneurysms in children and adolescents. The clinical picture, complicating factors and long-term prognosis]. PMID- 4024331 TI - [Sunshine and malignant melanoma. A possible connection between sunburn and the development of malignant melanoma]. PMID- 4024332 TI - [Acute pancreatitis in urban and rural regions]. PMID- 4024333 TI - [Technical failure following osteosynthesis of trochanteric fractures of the femur. A clinical follow-up study]. PMID- 4024334 TI - [Adenoma of the nipple and concomitant breast cancer]. PMID- 4024335 TI - [Glucagon and impacted food in the esophagus]. PMID- 4024336 TI - [Tuberous sclerosis. Report of a case with monstrous benign retroperitoneal tumor masses]. PMID- 4024337 TI - [Attempted suicide among children and adolescents. A follow-up study 1976-1983]. PMID- 4024338 TI - [Pattern of referral of patients with acute eye injuries. A regional study]. PMID- 4024339 TI - [Patients' evaluation of outpatient surgery]. PMID- 4024340 TI - [Sympathetic control of arteriole tone in peripheral tissue during orthostatic stress. Physiological and clinical aspects]. PMID- 4024341 TI - [Epidermolytic toxin. Dermatologic manifestations]. PMID- 4024342 TI - [Acid phosphatases and rectal examination. A study with immunologic analysis]. PMID- 4024343 TI - [Lamp oil poisoning in early childhood]. PMID- 4024344 TI - [Isosorbide-5-mononitrate. A metabolite of isosorbide dinitrate]. PMID- 4024345 TI - [Driving licence problems in diabetics. Rules, occurrence of accidents and legislation]. PMID- 4024346 TI - [Deaths in diabetics--forensic aspects. A retrospective study of diabetes found in forensic autopsies over a period of 25 years]. PMID- 4024347 TI - [The care of diabetics]. PMID- 4024348 TI - [Traumatic avulsion of nerve roots in the medulla. Increased occurrence among drivers of motorcycles and mopeds]. PMID- 4024349 TI - [Weever fish stings and their sequelae]. PMID- 4024350 TI - [C-reactive protein in acute appendicitis. A prospective blind study]. PMID- 4024351 TI - [Treatment of metastatic fractures of the femoral shaft by closed reposition and intramedullary nailing]. PMID- 4024352 TI - [Primary osteosynthesis of scaphoid bone fractures]. PMID- 4024353 TI - [Surgical treatment of hip arthrosis with hemi-arthroplasty]. PMID- 4024354 TI - [Microsurgical salpingostomy]. PMID- 4024355 TI - [Persistent foreign body of the small intestine]. PMID- 4024356 TI - [Aseptic bone necrosis in systemic lupus erythematosus. Relationship to glucocorticoid therapy]. PMID- 4024358 TI - [An experimental community psychiatry project in the counties of Brorup, Vejen and Holsted Ribe]. PMID- 4024357 TI - [Giant vesical calculus]. PMID- 4024359 TI - [Clinical ethics: the work of the physician]. PMID- 4024360 TI - [Suicide, economics and social environment in Quebec, 1950-1981]. PMID- 4024361 TI - [Health education, a new and improved version]. PMID- 4024362 TI - [Childhood poisoning in the Montreal region]. PMID- 4024363 TI - [Familial cancer. 1. Familial adenocarcinoma]. PMID- 4024364 TI - [Cervical and parasternal mediastinoscopy. Surgical technics in the examination of superior mediastinal lymph nodes]. PMID- 4024366 TI - [Wheezing? Whistling? Breathing with a whistling sound? Study of the word "siler" in medical terminology]. PMID- 4024367 TI - [Abstracts of reports. Association of Physician Microbiologists of Quebec. Annual meeting. Isle-aux-Coudres, Quebec, 30-31 May 1985]. PMID- 4024365 TI - [The association of diabetes mellitus, chronic renal insufficiency and reactional perforating collagenosis: apropos of a case]. PMID- 4024368 TI - [Psychopathology and violence: review of concepts and applications]. PMID- 4024369 TI - [Familial cancer. 2. The S.B.L.A. syndrome: sarcoma of the breast, brain, leukemia and adrenals]. PMID- 4024370 TI - [Ileo-anal anastomosis. Physiopathology and clinical application]. PMID- 4024371 TI - [Sports and the heart]. PMID- 4024372 TI - [Double-cup arthroplasty: analysis of 36 cases]. PMID- 4024373 TI - [Rational use of thallium-201 myocardial scintigraphy based on a statistical analysis: practical view]. PMID- 4024374 TI - [That breast cancer was a metastasis...but where was the primary tumor?]. PMID- 4024376 TI - [Apropos of nephromegaly in a child]. PMID- 4024375 TI - [The crying infant, or infantile colic]. PMID- 4024377 TI - Symposium on intraoperative consultation. PMID- 4024378 TI - The role of intraoperative consultation. AB - The urologist who has completed an approved residency training program and has been certified by the American Board of Urology is well prepared to meet the daily challenges presented by the practice of urologic surgery. In spite of this careful preparation, there are times in the operating room when intraoperative consultation is needed and will be of great help in managing the surgical problem encountered. Although intraoperative consultation is probably not used as often as it should be, it is the author's hope that the reader of this symposium will be a better consultant in the operating room when called and will also feel more comfortable about calling for help when it is needed. PMID- 4024379 TI - Intraoperative consultation for the kidney. AB - Unexpected renal masses, renal anomalies, and trauma to the kidneys or renal vessels discovered at exploratory laparotomy may prompt a surgeon to consult a urologist intraoperatively. The usual principles of urologic management apply in these cases, but the evaluation must be tailored to the intraoperative situation. Except in emergency cases, definitive treatment can be delayed safely until full urologic evaluation is possible. PMID- 4024380 TI - Intraoperative consultation for the bladder. AB - Iatrogenic bladder injury is a well-recognized complication of any pelvic operative procedure. When recognized and properly repaired at the time of injury, laceration of the bladder seldom leads to significant postoperative morbidity. In those rare instances in which bladder injury is unavoidable, the knowledge and application of proper surgical technique as well as appropriate intraoperative and postoperative management of the use of drains and catheters will minimize associated complications. PMID- 4024381 TI - Intraoperative consultation for the urethra. AB - The urologist is frequently summoned to the operating room to assist with urethral catheterization. This article presents the authors' method and techniques for dealing with the "impassible urethra." Oftentimes the patient has been traumatized. A sequential plan is presented that allows for maximal evaluation of the entire urinary tract along with eventual urethral catheterization. In the case of the disrupted urethra, diversion must be accomplished. The authors have found that the placement of a urethral catheter along with division of intact puboprostatic ligaments in the stable patient frequently limits the eventual morbidity of the trauma. PMID- 4024382 TI - Intraoperative consultation for surgery of the genitalia and genitourinary prostheses. AB - Patients with genitourinary prostheses, especially the hydraulic variety, will be encountered with increasing frequency in the future and present special problems to the urologist who is called in for intraoperative consultation. Knowledge of the design and operation of these devices, as well as certain operative principles unique to these prostheses, permits the urologist to deal effectively with these situations. PMID- 4024383 TI - Pediatric urologic intraoperative consultation. AB - As in adults, intraoperative consultations in children are not expected. If one has thought about possible situations in which consultations may occur, one may be prepared for the unusual event. Careful and thorough diagnosis will lead to correct conclusions, and we may then give appropriate consultation and fulfill a useful need to the operating surgeon and ultimately to the patient. PMID- 4024384 TI - Intraoperative consultation for the liver, biliary system, pancreas, duodenum, and spleen. AB - The urologist, when operating transabdominally, may unexpectedly encounter a cystic or solid mass in the liver, a dilated gallbladder or a gallbladder containing stones, or a mass in the pancreas, or may inadvertently injure the duodenum or spleen when mobilizing these organs for a nephrectomy or adrenalectomy. Discussed are some of these common liver, biliary, and pancreatic problems and their management, and the methods of management of duodenal and splenic injuries. PMID- 4024385 TI - Intraoperative consultation for the intestine. AB - There may be intestinal involvement during any procedure within the abdominal or pelvic cavity. Anticipation of this involvement with preoperative bowel preparation and a basic plan to meet the circumstances will minimize potential problems both in planned and unplanned situations. This article addresses the most common situations seen in urologic practice and describes the techniques to deal with them. PMID- 4024386 TI - Vascular problems in urologic patients. AB - Intraoperative vascular surgical consultation may be necessary if venous or arterial injury occurs during transabdominal urologic operations. Loss of blood usually can be controlled by simple digital compression until the consultant arrives, but urologists should be familiar with the principles of vascular reconstruction. Adequate exposure of the injured segment is essential, and the repair of major vessels must preserve patency as well as provide hemostasis. In this regard, patch angioplasty is sometimes necessary, and formal replacement with autogenous or prosthetic grafts may rarely be required. Blunt arterial trauma can precipitate distal arterial embolization, a complication that usually is not suspected until the immediate postoperative period. Although salvage should be managed by a vascular surgeon, urologists must be alert for the early signs of acute extremity ischemia after extensive retraction has been used deep in the pelvis, particularly in elderly or atherosclerotic patients. Considering the established diagnostic accuracy of roentgenographic studies presently employed in the fields of urology and vascular surgery, preoperative planning should limit the number of urgent intraoperative consultations between members of these two specialties. Each may have valuable advice to offer the other concerning the treatment of unusual problems involving obstructive uropathy, aortic aneurysms, and occlusive arterial disease, and their cooperative effort is especially important in the management of renal revascularization. PMID- 4024387 TI - The thoracic cavity, a troublesome neighbor. Intraoperative consultation by the thoracic surgeon. AB - There is usually little need for intraoperative collaboration between the thoracic surgeon and his urologic colleague. However, situations occasionally arise in the urologist's operating room that require consultation with a thoracic surgeon or the use of thoracic surgical techniques. These techniques may be required during intrathoracic complications of common anesthetic procedures, or when renal pathology is extensive and demands cooperation between the specialties. The propensity of renal-cell carcinoma to extend via the renal vein into the inferior vena cava and right atrium may, on occasion, require direct surgical cooperation between the cardiac and urologic surgeon to remove safely large tumors that extend into and perhaps adhere to the right atrium. PMID- 4024388 TI - Pediatric surgical intraoperative consultations. AB - Six problems that have surgical implications and that may be encountered unexpectedly during urologic procedures in infants and children are discussed. Evolving practice and increased knowledge about these conditions require that the consultant's opinion regarding their management be updated. Discussed are the indications for concomitant appendectomy in young patients and the pros and cons regarding removal of a Meckel's diverticulum encountered unexpectedly. The necessity for and techniques used to preserve the spleen in the face of operative injury, presence of a splenic cyst, or a wandering spleen are discussed. Finally, the implications of finding a rotational abnormality of the gut are reviewed. PMID- 4024389 TI - Intraoperative consultation for gynecologic disorders. AB - A careful history and pelvic examination will allow a more meaningful and thorough preoperative evaluation. It will also greatly reduce the need for subsequent intraoperative consultation for unexpected gynecologic disorders. Medicolegal disasters resulting from unconsented castration or loss of reproductive function may be avoided as well. When unpredictable circumstances are encountered, the urologist should be able to recognize them and know when further expertise is required. In most situations an exact diagnosis can usually be established without sacrificing reproductive or endocrinologic function. Although definitive therapy may need to be delayed and further surgery performed, this is more acceptable in the face of life-threatening disease than the consequences of unnecessary gynecologic surgery or debilitation. PMID- 4024390 TI - Intraoperative anesthetic consultation. AB - This article deals with consultation between anesthesiologists and urologic surgeons. Some of the subjects discussed represent problems that occur commonly, such as cardiac arrhythmias and intraoperative hypertension. Other subjects, though representing less common problems, have much more serious consequences and thus should be brought to the attention of surgeons. This latter group includes malignant hyperthermia, hyponatremia during transurethral prostatic resection, and cardiac arrest. PMID- 4024391 TI - Operating room consultation by the pathologist. AB - Intraoperative consultation by the pathologist should ensure that adequate diagnostic tissue has been obtained, should facilitate the proper handling of tissue, and should provide accurate, prompt histopathologic diagnosis by frozen section technique. This article discusses the pathologist's role in diseases of the urinary tract, male genital organs, adrenal gland and retroperitoneum. PMID- 4024392 TI - Legal implications of intraoperative consultation. AB - As medicine evolves, not only the complexity of its technology but the complexity of the legal relationships between its practitioners increases. The legal doctrines and principles involved in this area are not themselves new. However, the myriad relationships between the players in this setting give rise to some of the most interesting factual and analytical questions in the law. With a sanguine outlook, it is to be hoped that the law's determination of responsibility and liability in this complicated area will be fair, rational, and constructive. PMID- 4024393 TI - Preliminary results on the use of the humoral immune response as a serum marker in patients with bladder tumors. AB - An immunoassay using a human bladder tumor tissue culture cell line (J-82) as antigen and a modified avidin-biotin-complex (ABC) method were used to examine human serum samples. Optical density (OD) of 26 serum samples obtained from 19 patients with bladder tumors had a mean OD of 458 +/- 71 SD (328-570). This is significantly higher (p less than 0.0005) when compared to the mean OD of 172 +/- 49 SD (107-301) found in serum samples from 28 patients with tumors other than bladder cancer and to the mean OD of 207 +/- 48 SD (136-310) of serum samples from 25 healthy donors. Thirty-one serum samples from 21 patients who had a bladder tumor surgically removed 1 to 36 months before were, with 2 exceptions, also higher than 320 (mean 412 [248-550]). All serum samples of patients with presence of a bladder tumor above the cut-off point of 320 and those from the 2 control groups below it shows, thus far, a high sensitivity as well as specificity of the method used and encourages further assessment of its potential usefulness as a serum marker assay in patients with bladder cancer. PMID- 4024394 TI - Serum half life of prostatic acid phosphatase. AB - Traumatic manipulation of the prostate can cause elevated prostatic acid phosphatase (PAP) values. To avoid falsely elevated PAP values after prostatic trauma we studied the serum half life of PAP and the time taken to return to preoperative levels in patients undergoing transurethral resection (TUR-P). Although we observed a broad variation in peak PAP values the half life of PAP is fairly constant at about 1.1-2.6 h. Preoperative values were reached within 30 h. We conclude that PAP determinations can safely be carried out 30 h after prostatic trauma without any risk of falsely elevated PAP values. PMID- 4024395 TI - Simultaneous determination of six tumor markers in patients with prostatic carcinoma and bladder tumors. AB - Serum levels of fucosyltransferase (FT), phosphohexoseisomerase (PHI), tissue polypeptide antigen (TPA), Tennessee antigen (TAG), carcinoembryonic antigen (CEA) and prostatic acid phosphate (PAP) were determined in 75 healthy individuals and in 86 patients with prostatic carcinoma and 38 patients with bladder tumors. The discrimination capacities of the different markers were compared by using inverse distribution plots. At a rate of 5% false positive values the sensitivities for bladder tumors were: FT 30%, TPA 24%, CEA 16%, TAG 15%. The sensitivities for prostatic carcinoma were: PAP 63%, PHI 36%, TPA 18%, CEA 14%, TAG 14%. PMID- 4024396 TI - Value of cystourethroscopy in the assessment of children with recurrent urinary tract infections and/or enuresis. AB - Forty-one children ages 6-14 years consecutively referred for recurrent urinary tract infections (RUTI) and/or enuresis constituted the study group. Cystourethroscopy (CUS) was carried out in 40 children and pathologic findings were revealed in 70% of children with RUTI in the absence of vesico-ureteral reflux (VUR). However, only in 4 patients did CUS influence treatment. Based on these data we conclude that routine CUS is not justified in the evaluation of this group of children unless anatomical infravesical lesions are suspected. VUR was proven in 44% of children with RUTI. In 86% of these ureters abnormal ureteric orifices were demonstrated. We therefore find CUS to be valuable in the assessment of children with both RUTI and VUR, because this examination is helpful in selecting patients who might need operation for severe VUR. CUS was not of therapeutic benefit to children with enuresis. Five patients with macroscopic haematuria during urinary tract infection were not managed differently following CUS. PMID- 4024397 TI - The screening of more than 2,000 schoolgirls for bacteriuria using an automated fluorescence microscopy system. AB - After initial evaluation of a manual fluorescence microscopy system on a variety of urines the method was automated and subsequently tested in a population survey of urinary tract infection in schoolgirls. This automated Bactoscan system allowed a rapid analysis of urine samples and with the introduction of modifications to the staining protocol it correctly eliminated 91% of samples as being not significantly infected. PMID- 4024398 TI - A survey of bacteriuria in 2,234 schoolgirls in a Scottish new town. AB - The prevalence of urinary tract infection in a modern Scottish town has been ascertained in female school children aged 5-12. In 2,234 girls the initial prevalence of urinary tract infection is 3.3%. In addition to the information on urinary tract infection the social and personal history was available including data on incontinence, enuresis and current antibiotic therapy. The necessity to have a system available which allows a cheap and rapid assessment of population surveys is made. PMID- 4024399 TI - Pelvic lymphadenectomy for carcinoma of prostate. AB - Pelvic lymphadenectomy was performed in 187 patients as a staging procedure for carcinoma of the prostate. Clinical impression of lymph nodes during dissection appears to be inaccurate in a large number of patients. We therefore believe that if radical surgery is planned for clinically localized tumor, the histologic status of the removed nodes should be confirmed before surgical extirpation of the tumor. PMID- 4024400 TI - On percutaneous drainage of retroperitoneal collections: when is primary surgical drainage preferable? AB - Percutaneous drainage of retroperitoneal collections is a method employed with an ever-increasing frequency. The indication for primary surgical drainage of these collections is rapidly decreasing. Herein we describe what we consider to be the indications for primary surgical drainage of retroperitoneal collections illustrated by the recurrence of the abscess in 3 of our patients following adequate primary percutaneous drainage. PMID- 4024401 TI - Pyelovesicostomy: an alternative to ureteropelvic junction-plasty in pelvic ectopic kidneys. AB - Pyelovesicostomy was performed in 2 cases of hydronephrosis in pelvic kidneys secondary to ureteropelvic junction obstruction. In the first patient, who presented with a solitary kidney, the procedure was done after failure of a dismembered pyeloplasty, while in the second patient the procedure was performed electively. Both patients had sterile urines and stable renal function, although some dilatation persisted in the first case. The indications and the functional aspects of this surgical solution are discussed. PMID- 4024402 TI - Dissolution of uric acid calculi with intravenous 1/6 molar lactate. AB - The use of intravenous 1/6 molar sodium lactate for dissolution of uric acid calculi is reported in 4 patients. All presented with a urine pH of 5. The calculi were located in the proximal ureter in 2 patients and in the renal pelvis in the other 2 patients. After infusion of 1/6 molar lactate, rapid alkalinization of the urine to pH 8 was achieved and maintained. The mean time required for dissolution of the calculi was 6.2 days precluding the need for surgical intervention. The mechanism of action of lactate is oxidative conversion to bicarbonate, providing a sustained alkaline urine. While our patients experienced no metabolic complications, one should monitor serum electrolytes, blood pressure, and fluid balance, particularly in cardiac-compromised patients. PMID- 4024404 TI - Percutaneous nephrolithotomy. With emphasis on large renal stones. AB - With utilization of safety guide wire, dilator (up to 36F), and Mazzariello Caprini forceps, percutaneous removal of renal stone was successfully performed in 18 cases, including 5 cases with staghorn calculus, although parts of the staghorn calculus were left in 4 cases. Attempts at stone extraction were performed on the day nephrostomy was made. All of the renal stones excluding staghorn calculi were removed without disruption followed by satisfactory postoperative renal function. Unexpectedly Kocher forceps was found to be a useful and relatively safe instrument for quick fragmentation and removal of staghorn calculi. PMID- 4024403 TI - Erectile dysfunction in diabetes and hypertension. AB - By direct interrogation and specific questions, the erectile function of 1,128 male adults, aged sixteen to eighty years and over, was elicited. The erectile function was based on ability to develop an erectile angle of 90 degrees and more, and this was used for classification purposes. Three hundred seventeen consecutive, unselected male diabetics and 117 nondiabetic male hypertensives were compared with 635 consecutive adult males with neither diabetes nor hypertension. Our results indicate that erectile dysfunction, partial or complete, is more prevalent in diabetics compared with nondiabetics of the same age groups. An unexpected finding was a meager relationship between hypertension and erectile disability. Antihypertensive drugs were responsible for only 2 cases of erectile dysfunction in our male hypertensive patients. The negative impact of age was noted in all age groups and in those with or without diabetes or hypertension. PMID- 4024405 TI - Complete penoscrotal transposition. AB - A patient with complete penoscrotal transposition is described. We believe this represents the first such case associated with a chromosomal anomaly. A review of the literature is given. PMID- 4024406 TI - Preservation of periprostatic autonomic nerves during total perineal prostatectomy by intrafascial dissection. AB - A modification of Young's total perineal prostatectomy technique is described to prevent damage to the apical branches of the cavernous nerves. Based on anatomic relationships between investing prostatic fascial layers and the neurovascular bundle, emphasis is placed on division of the apical prostatic urethra between the anterolateral endopelvic fascia and Denonvilliers fascia (intrafascial dissection) in avoidance of the apical nerves. Vertical incision in the fused distal portion of Denonvilliers fascia is necessary to make this dissection atraumatic regarding the adjacent paraprostatic neurovascular bundle. Clinical application of this completely intrafascial prostatic dissection is exemplified. It is concluded that careful modification of Young's technique of total perineal prostatectomy may result in increased postoperative potency rates. PMID- 4024407 TI - Idiopathic segmental renal infarction. PMID- 4024408 TI - Eosinophilic cystitis. PMID- 4024409 TI - Congenital midureteral strictures. AB - A case is reported of a fifteen-year-old female with left midureteral congenital stricture and a contralateral single blind-ending ureter with a small atrophic right kidney. The possible etiology is presented. PMID- 4024410 TI - Kaposi sarcoma limited to glans penis. AB - Two cases of Kaposi sarcoma are presented. In each case the lesion had a bluish discoloration and was painless. Excision of lesions with wider margins was adequate therapy. PMID- 4024411 TI - Condyloma acuminatum in children. AB - A case of extensive venereal warts in a nine-year-old female patient is presented. Transmission, pathology, and therapy are discussed. PMID- 4024412 TI - Percutaneous placement of suprapubic cystostomy tube. PMID- 4024413 TI - Saha Bladder Neck Spreader. PMID- 4024414 TI - Removal of internal ureteral stent under fluoroscopic guidance. PMID- 4024415 TI - Malignant Sertoli cell tumor of testicle. AB - The eleventh case of malignant Sertoli cell tumor of the testicle is described. The tumor displayed malignant character with local invasion into the epididymis. Retroperitoneal lymph node dissection revealed a malignant deposit around the left renal artery. PMID- 4024416 TI - Case profile: spontaneous retrograde extravasation of kidneys following retrograde cystography. PMID- 4024417 TI - Relative role of abdominal pelvic CT and lymphangiography in staging of testicular seminoma. AB - Sixty patients with testicular seminoma were reviewed regarding the evaluation of the retroperitoneal lymph nodes. Thirty-four of these patients had both abdominal pelvic computerized tomography (APCT) scan and bipedal lymphangiography (LAG). In 21 patients, the results of the two studies were in agreement. However, 11 patients had positive LAG and negative APCT, while only 2 had a positive APCT and negative LAG. We recommend that patients with testicular seminoma have an APCT. If findings are negative, LAG should be done. PMID- 4024418 TI - Urologic complications after surgery on lumbosacral spine. AB - Forty-five of 74 patients (60%) postsurgery for disk disease showed findings of neurogenic bladders. Sixty-nine of these patients had no complaints before surgery and presented with complaints only after surgery. We believe this is a high surgical morbidity, and all patients should have a presurgical urodynamic diagnostic evaluation to aid in selection of patients in whom surgery will be most helpful and to establish a presurgical baseline for further postsurgical urodynamic comparison. PMID- 4024419 TI - Pathogenicity of Isospora suis in gnotobiotic and conventionalised piglets. AB - Isospora suis is unequivocally a primary pathogen of swine. Inoculation of I suis in conventionalised and germ-free piglets caused a biphasic disease course with marked diarrhoea, villous atrophy and necrosis of the intestinal epithelium at four to six and eight to 10 days after inoculation. The presence of a normal bacterial flora markedly (P less than 0.05) influenced the survival rate of piglets but did not appear to affect the histopathological changes observed. Mild limited focal necrosis and bile stasis were present in the liver at eight to 10 days after inoculation. In this period there was also ectasia of lymph vessels in the intestinal lymph nodes. PMID- 4024421 TI - Eosinophilic leukaemia in the cat: a case report. PMID- 4024420 TI - Effect of flucythrinate impregnated ear tags on fly attack in cattle. PMID- 4024422 TI - Survey of fungal isolates from alopecic and asymptomatic dogs. PMID- 4024423 TI - Selenium poisoning in lambs. PMID- 4024424 TI - Acquired diaphragmatic hernia in a stallion. PMID- 4024425 TI - Tetanus in a cat. PMID- 4024426 TI - Visually evoked responses during slaughter. PMID- 4024427 TI - Prostaglandins warning. PMID- 4024429 TI - Sir William Weipers lecture. The price of freedom. PMID- 4024428 TI - A new transmissible agent causing acute hepatitis, chronic hepatitis and cirrhosis in dogs. AB - There is a hepatitis of dogs which occurs in acute, persistent and chronic forms. Histological studies of spontaneous cases suggested that several apparently diverse hepatic diseases might be stages of one process. This was also implied by follow up studies and case histories: acute non-lethal episodes were followed later by the development of chronic hepatitis, cirrhosis and liver failure. Serum was taken and homogenates of liver were made from three field cases representing different putative temporal stages of the complex. These were injected into experimental dogs and a hepatitis was induced in all. The cytopathological and histological changes were the same in all animals and were identical to field cases. Acute lethal disease and persistent infections were produced. Two second passages were carried out and an identical condition was induced, characterised by recurrent episodes of subclinical hepatitis and persistent infection. It is suggested that the disease might be named canine acidophil cell hepatitis in view of the pathognomonic cytopathology. Specific morphological criteria have been established for this hepatitis. PMID- 4024430 TI - Feeding bovine colostrum to lambs. PMID- 4024431 TI - Suspected selenium poisoning in lambs. PMID- 4024432 TI - Case of quadrilateral flexural contracture in a 10-year-old pony. AB - The management of a case of quadrilateral flexural contracture in a 10-year-old pony is described. The animal was restored to normal appearance and function through a combination of surgical desmotomy and management techniques; the importance of analgesia and exercise as adjuncts to surgery is emphasised. The aetiology and pathogenesis of the condition in the immature animal and the adult is compared and a possible association is made between this condition and palmar fibromatosis (Dupuytren's contracture) occurring in man. PMID- 4024433 TI - Apparent reinfection of enzootic-pneumonia-free pig herds: search for possible causes. AB - In a control scheme for enzootic-pneumonia-free herds, run by the Pig Health Control Association, a detailed study was made of 55 herds that developed enzootic pneumonia without a simple explanation. These herds were compared with 57 herds that were still free from enzootic pneumonia in mid-1984. A high standard of precautions against the risk of infection being transferred by people and fomites seemed to confer no obvious benefit. This observation was in keeping with in vitro studies which showed that, although Mycoplasma hyopneumoniae could survive for a long time in favourable liquid medium, it could not be recovered from material such as cloth, once the culture had become dry. Under field conditions, the organism would probably cease to be infective within 48 hours. The organism survived particularly well in rain water at lower temperatures, however, and transmission via moist cold air seemed a possibility. There was a tendency for breakdowns to start in the autumn and winter, particularly in highly secure units, and several farmers associated colder misty conditions with the arrival of infection. One herd was probably infected by an imported boar and the very close proximity of foreign pigs, such as in slaughterhouse transport, seemed the most likely explanation in 15 other herds. One herd was replaced without this danger being attended to and it soon broke down again, whereas the three herds in this category that have survived after replacement all had this risk eliminated. Data was available on 37 of the 39 remaining herds to compare them with the 57 surviving herds, using a risk index based on the proximity of other pig units.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4024434 TI - Association between urinary incontinence and spaying in bitches. PMID- 4024435 TI - Bovine parvovirus. PMID- 4024436 TI - Urethral obstruction in a cow. PMID- 4024437 TI - Venous administration of hypertonic fluids. PMID- 4024438 TI - Hedgehog information. PMID- 4024439 TI - Lameness following mating. PMID- 4024440 TI - Maggot control. PMID- 4024441 TI - Tetanus in a cat. PMID- 4024442 TI - Hereditary cataract in the standard poodle. PMID- 4024443 TI - Selective funding and the future of the veterinary profession. PMID- 4024444 TI - Parvovirus vaccination. PMID- 4024445 TI - Filaroides hirthi in a British bred beagle dog. AB - Filaroides hirthi was identified in large numbers in the lungs of a British bred beagle dog that had received 10 monthly intra-articular injections of a corticosteroid. The dog was terminally hyperpnoeic and eosinophil and reticulocyte counts were raised. At autopsy, the lungs failed to collapse and minute black and red foci were found throughout the lung parenchyma. These foci were identified histologically as parasites and focal haemorrhage. Migrating larvae were found in the liver and mesenteric lymph nodes. F hirthi has not previously been definitively identified in British dogs and the principal features of its identification and control are discussed. PMID- 4024446 TI - Toxicity and interaction of topical organophosphate insecticide dichlorvoscrotoxyphos and phenothiazine anthelmintic in sheep previously exposed to both drugs. AB - Toxicity and interaction of topical application of dichlorvoscrotoxyphos (D-C) insecticide and phenothiazine anthelmintic (PTZ) given in the diet were studied in 4 groups of 4-5 lambs each that had had prior drug exposure. In a study reported previously each lamb in groups 1 and 2 was sprayed with 3 biweekly topical applications of 1550 ml of 0.25% D-C emulsion. Groups 1 and 3 were treated with PTZ (12.5 g/sheep initially and 4 days later with 6.25 g every 3 days for 9 treatments). Group 4 was the control. Following termination of that study the animals were given a 30-day nonmedicated period and reused in the present study as described below. Each lamb in group 1 and 3 was challenged with PTZ given in the diet (1g/sheep/day for 3 days). On the third day of PTZ administration, each lamb in group 1 and 2 was sprayed with 1 gallon of 0.25% D-C emulsion. The 4th group served as a control. Following D-C spray, clinical signs of toxicosis were seen within 17 min in 56% of the exposed lambs regardless of concurrent PTZ treatment. The erythrocyte acetylcholinesterase (EACE) activities of the D-C exposed groups were significantly (P less than 0.05) depressed on post treatment days (PTD) 1 and 3 regardless of the PTZ treatment. The base-line EACE values were reestablished on PTD 18. The PTZ alone was not toxic and did not inhibit EACE activity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4024447 TI - Protective effect of activated charcoal in cattle poisoned with atrazine. AB - Six heifers were poisoned with a lethal dose of atrazine. Three animals were treated daily for 4 days with activated charcoal. The untreated animals died within 3 days, whereas the treated animals survived the 14-day observation period. Hematology, blood chemistry and pathology findings are reported. PMID- 4024448 TI - The future of toxicology. PMID- 4024449 TI - Cell-mediated immune response to rabies virus in dogs following vaccination and challenge. AB - Peripheral blood lymphocytes (PBL) from non-vaccinated dogs and from dogs either vaccinated intramuscularly (IM) or subcutaneously (SC) with an inactivated rabies virus vaccine (Rabguard-TC, Norden Laboratories, Lincoln, NE) or intramuscularly with an attenuated rabies virus vaccine (Endurall-R, Norden Laboratories, Lincoln, NE) were exposed in vitro to rabies virus. Blastogenesis of PBL was measured by incorporation of 3H-thymidine into the DNA of proliferating cells in the presence of a suboptimal concentration of phytohemagglutinin (PHA). Following the first vaccination, there was no difference in the blastogenic response of lymphocytes from dogs vaccinated IM with either the inactivated or attenuated rabies virus vaccines. The inactivated rabies vaccine stimulated as great or greater blastogenic response when it was given SC. The PBL from non-vaccinated control dogs were not stimulated by rabies virus. Dogs vaccinated with the inactivated vaccine developed a lymphocyte blastogenic response to rabies virus following challenge with virulent street rabies virus. Nonvaccinated control dogs did not develop a lymphocyte blastogenic response to rabies virus following challenge with virulent street rabies virus. PMID- 4024450 TI - A comparative study of complement activation. AB - Antisera to sheep erythrocytes (E) were raised in cattle, rabbits, mice, hamsters, guinea-pigs, ferrets, badgers, hedgehogs and fowls. Cross activation of total haemolytic complement (THCA) examined all combinations of sensitized sheep E and normal sera (including human); kinetic assays examined the lysis of E sensitized with rabbit antibodies. From the same species, all combinations of normal serum and xenogeneic E were used to measure total alternative pathway activity (TAPA); TAPA was also activated by rabbit and sheep E in titrations and in agarose gels, and examined kinetically against rabbit E. Ox, rabbit and fowl sera were low in THCA, guinea-pig complement was universally active, while human complement showed marked selectivity; ferret, badger and hedgehog sera were activated to high titres but probably via the alternative pathway. In studies of TAPA an inverse relationship existed between serum complement activities and the activating abilities of E from the same species. The most efficient activators of alternative pathway were E from rabbits and laboratory rodents, while the sera with broadest response were badger, ferret and fowl. Kinetic studies of TAPA showed that initiation of lysis and subsequent completion of lysis could occur with different efficiencies, suggesting these events reflected separate events in complement activation. PMID- 4024451 TI - Equine alternative pathway activation by unsensitized rabbit red blood cells. AB - The equine alternative complement pathway has been partially characterized and compared to the equine classical activation pathway. A dose-dependent lysis of RbRBC was observed with peak lytic values noted within 10 minutes at 37 degrees C when rabbit red blood cells (RbRBC) were used as an alternative pathway activator. Sheep red blood cells (SRBC) sensitized with rabbit hemolysin or partially purified equine IgM antibodies were equally sensitive to lysis. Dilution of the commercial hemolysin by 1/5 reduced lysis from 90% to 38% in the presence of constant cell numbers. Hemolysis of SRBC peaked at 10 minutes and the majority of lysis occurred within 10 minutes. Dilution of equine sera by as little as 1/5 decreased hemolytic activity for SRBC to 21.5% from greater than 90% with undiluted sera. The alternative pathway protein, equine factor B, was tested using RbRBC and monitored by its differential susceptibility to heat treatment at 50 degrees C. This treatment led to almost complete inactivation after a 15-minute incubation. An apparent heat-dependent decay of certain classical pathway components was also observed after 50 degrees C treatment. This sensitivity was indicated by a reduction in the lytic activity for sensitized SRBC. Treatment for 15 minutes at 56 degrees C with either RbRBC or SRBC was sufficient to abolish hemolytic activity in all equine sera tested. Chelation of cations with 0.04 M EDTA blocked expression of alternative and classical pathway activation; however, chelation of Ca++ ions with 10 mM EGTA containing 1 mM Mg++ ions permitted lysis of the RbRBC but not the SRBC. A dose-related Mg++-ion dependence for RbRBC hemolytic activity was observed as the concentration of Mg++ was increased to 1.0 mM. In addition, our results obtained with pre-colostral foal serum strongly suggest that natural antibody to RbRBC was of little importance in the lysis observed with these cells. These results also show that the equine alternative pathway activation may require Ca++ ions. If Ca++ ions are required, the equine alternative pathway is quite different from any other mammalian complement system so far described. Our results suggest that the alternative pathway of activation is of major importance in the equine complement system. Confirmation of this hypothesis requires both purification of the components involved as well as further characterization. PMID- 4024452 TI - RNA sequence and transcriptional properties of the 3' end of the Newcastle disease virus genome. AB - The 3' end of the genomic RNA of Newcastle disease virus (NDV) has been sequenced and the leader RNA defined. Using hybridization to a 3'-end-labeled genome, leader RNA species from in vitro transcription reactions and from infected cell extracts were found to be 47 and 53 nucleotides long. In addition, the start site of the 3'-proximal mRNA was determined by sequence analysis of in vitro [beta 82P]GTP-labeled transcription products. The genomic sequence extending beyond the leader region demonstrated an open reading frame for at least 42 amino acids and probably represents the amino terminus of the nucleocapsid protein (NP). The terminal 8 nucleotides of the NDV genome were identical to those of measles virus and Sendai virus while the sequence of the distal half of the leader region was more similar to that of vesicular stomatitis virus. These data argue for strong evolutionary relatedness between the paramyxovirus and rhabdovirus groups. PMID- 4024453 TI - The site of commencement of retinal maturation in the rabbit. AB - In the developing retina of the rabbit the ganglion cell layer can first be identified between E(embryonic day) 20 and 24, but the regional variations found in the adult retina, particularly the visual streak, are not well developed until shortly before birth. At about E31, the last day of gestation, the laminar structure of the retina begins to mature, cytogenesis begins to cease and the outer plexiform layer starts to form. These processes commence in far temporal retina, at or near the site of the area centralis, and spread preferentially along the visual streak. PMID- 4024454 TI - Morphological correlates of Y, X and W type ganglion cells in the cat's retina. AB - After physiological recordings with microelectrodes containing horseradish peroxidase (HRP), morphological properties of Y, X and W type ganglion cells were studied on flat-mounted cat's retinas. While all the Y cells (N = 9) and the X cells (N = 8) revealed alpha and beta cell morphologies of Boycott and Wassle [J. Physiol. 240, 397-419 (1974)], respectively, W cells (N = 4) revealed various morphological types including their gamma and delta cells. The Y cells were larger than X cells in soma diameter, but the W cells were of the same range as X cells. Electron microscopic observations of the cross-sectioned nerve fiber bundles provided evidence for the segregation of axon diameters into the three groups corresponding to Y, X and W axons. It was discussed that functional trichotomy of retinal ganglion cells is related to the differentiation more in axon diameter rather than in soma size. PMID- 4024455 TI - Projection of morphologically identified superior colliculus neurons to the lateral posterior nucleus in the cat. AB - Using the intracellular recording and staining techniques we studied types of superior colliculus cells which project to the ipsilateral nucleus lateralis posterior (LP) and the nature of retinal afferent inputs to them. Five morphologically identified colliculus cells were antidromically driven by stimulation of the tectorecipient zone of the LP. The nature of retinal afferent inputs to these cells was determined by measuring conduction velocity between the optic chiasm and the optic tract. Four of the five, innervated by W-retinal ganglion cells, were narrow-field vertical and wide-field vertical cells, located in the upper and lower parts of the superficial gray layer. The remaining one, innervated by Y-fibers, was a large narrow-field vertical cell, located in the lower part of the same layer. PMID- 4024456 TI - Ascending, descending and local control of neuronal activity in the rat lateral geniculate nucleus. AB - Mechanisms of control for activities of relay neurons (P-cells) in the rat dorsal lateral geniculate nucleus (LGNd) are surveyed with special reference to ascending projection arising from the locus coeruleus (LC), the local projection from the visual portion of the thalamic reticular nucleus (vTRN) and the descending projection from the visual cortex (VC). Noradrenaline released from terminals of LC neurons exerts a facilitatory influence on P-cell activity via alpha-receptors. A recurrent projection of vTRN neurons on P-cells is inhibitory, utilizing GABA as a transmitter. P-cells receive an excitatory input from corticothalamic neurons of VC. However, in many P-cells the corticofugal excitation is counterbalanced by inhibition arising in vTRN neurons which are invariably exited by the collateral branches of the corticogeniculate axons. Thus, LGNd is not a simple relay station, but various modifications of visual information are made in this nucleus. PMID- 4024457 TI - Organization of geniculate inputs to visual cortical cells in the cat. AB - Neuronal connectivity between a geniculate cell and a striate cortical cell was examined by cross-correlograms between their impulse activities. Delayed positive correlations were found in 82 pairs, and the onset delay of the positivity was short enough in 65 pairs to infer that the geniculate cell monosynaptically excited the cortical cell. These monosynaptic excitations were found in both simple and complex cells. By determining connectivity of a cortical cell with multiple geniculate cells, the convergence of X and Y geniculate cells and that of on-center and off-center geniculate cells was demonstrated in several striate cells. PMID- 4024458 TI - GABAergic inhibition and orientation selectivity of neurons in the kitten visual cortex at the time of eye opening. AB - Effects of iontophoretic application of gamma-aminobutyric acid (GABA) and its antagonist, N-methyl-bicuculline (BIC), on visual responses of striate cortical neurons were studied in kittens 6-13 days old. Visually responsive cells were classified into three groups, i.e. orientation-selective, orientation-bias and nonoriented cells. In almost all of the orientation-selective cells, their responses were completely suppressed by GABA while the majority of the others were not significantly or only weakly suppressed. An application of BIC abolished or reduced the selectivity of all the orientation-selective cells but did not affect any of the nonoriented cells tested. These results suggest that GABAergic inhibition already operates on a group of cortical neurons to make them orientation-selective at the time of eye opening, but such an action of GABA on other groups of neurons develops later. PMID- 4024459 TI - Responses of neurons in visual cortex (V1 and V2) of the alert macaque to dynamic random-dot stereograms. AB - A substantial proportion of both simple and complex neurons in the cortex subserving central vision are differentially sensitive to binocular disparity of isolated line patterns (local stereopsis), a sensitivity based on a positional disparity between the neuron's receptive fields in the two eyes. In addition, a subset of cortical neurons, nearly all complex neurons, responds to dynamic random-dot stereograms containing no depth cues other than disparity. These neurons are capable of signaling the correct binocular matches among a multitude of false matches in the stereograms (global stereopsis). The discovery of cyclopean neurons in striate cortex, at early stages of the processing neural network for stereoscopic vision provides a new insight of the basic neural mechanisms underlying binocular depth perception. PMID- 4024460 TI - Responsiveness of Clare-Bishop neurons to visual cues associated with motion of a visual stimulus in three-dimensional space. AB - Photic responsiveness of cells in the medial bank of the lateral suprasylvian cortex (Clare-Bishop area) was studied using a three-dimensional visual stimulator that reproduced two visual cues (motion disparity and change in size) for perception of three-dimensional motion of a visual stimulus. About one third of them (48/148) were selectively responsive to motion disparity corresponding to approaching (AP cells, n = 30) or recessive motion (RC cells, N = 18), another half to motion of retinal images in the same direction between the two eyes corresponding to fronto-parallel motion (FP cells, n = 75), and the remaining cells were rather equally responsive to these types of stimuli (NS cells, n = 25). More than a half of the AP (19/30) or RC (11/18) cells were also responsive to increase or decrease in stimulus size, respectively, and they were optimally activated by a combination of the motion and size stimuli while relatively few FP and NS cells were sensitive to change in stimulus size. These findings indicate that the Clare-Bishop cells encode three-dimensional motion on the basis of photic responsiveness to the motion and size cues. PMID- 4024461 TI - Laminar segregation of color cells in the monkey's striate cortex. AB - In the monkey's striate cortex concentric cells with double opponent color properties were restricted to layers 4A and 4C beta; this cell type was also found in the lower half of 4C alpha but there it was always of the broad band class. Concentric cells of any type were absent from 4B. Simple cells were found in abundance in 4B and upper 4C alpha and were always broad band while those few found in 4A and 4C beta were usually double opponent color but sometimes were broad band. Color-sensitive complex and hypercomplex cells were found in the supragranular and infragranular layers (2, 3, 5 and 6). Double opponent concentric cells were occasionally seen in the supragranular layers but never in the infragranular laminae. PMID- 4024462 TI - Neuropsychological basis of pattern vision in macaque monkeys. AB - The central mechanisms of underlying pattern vision in macaques (rhesus and Japanese monkeys) were investigated behaviorally and electrophysiologically. A series of studies indicated that there are two major processes underlying pattern vision. One of two processes is the process of attending selectively to pattern cues at background, with which inferior parietal cortex is concerned predominantly. The other is the process of pattern perception and cognition, in which inferotemporal cortex is involved closely. PMID- 4024463 TI - Contour, color and shape analysis beyond the striate cortex. AB - The corticocortical pathway from striate cortex into the temporal lobe plays a crucial role in the visual recognition of objects. Anatomical studies indicate that this pathway is mainly organized as a serial hierarchy of multiple visual areas, including V1, V2, V3, V4, and inferior temporal cortex (IT). As expected from the anatomy, we have found that neurons in V4 and IT, like those in V1 and V2, are sensitive to many kinds of information relevant to object recognition. In the spatial domain, many V4 cells exhibit length, width, orientation, direction of motion and spatial frequency selectivity. In the spectral domain, many V4 cells are also tuned to wavelength. Thus, V4 is not specialized to analyze one particular attribute of a visual stimulus; rather, V4 appears to process both spatial and spectral information in parallel. A special contribution of V4 neurons to visual processing may lie in specific spatial and spectral interactions between their small excitatory receptive fields and large silent suppressive surrounds. Thus, although the excitatory receptive fields of V4 neurons are small, the responses of V4 neurons are influenced by stimuli throughout a much larger portion of the visual field. In IT, neurons also appear to process both spatial and spectral information throughout a large portion of the visual field. However, unlike V4 neurons, the excitatory receptive fields of IT neurons are very large. Many IT neurons, for example, are selective for the overall shape, color, or texture of a stimulus, anywhere within the central visual field. Together, these results suggest that within the areas of the occipito-temporal pathway, many different stimulus qualities are processed in parallel, but the type of analysis may become more global at each stage of processing. PMID- 4024464 TI - Neural mechanisms of space vision in the parietal association cortex of the monkey. AB - Functional properties of visual and eye-movement-related neurons of area 7a were studied in alert behaving monkeys. Visual fixation (VF) neurons had selectivity in the direction and/or distance of gaze, signaling the spatial position. Visual tracking (VT) neurons had selectivity in the direction of movement, signaling the movement in space. Many passive visual (PV) neurons were suppressed during eye movement, discriminating real from "self-induced" movement. A group of PV neurons sensitive to the depth movement responded to the changing image size. A group of neurons sensitive to the rotation of visual stimulus in space were also found in area 7a. PMID- 4024465 TI - Distribution and organization of visual and auditory neurons in the monkey prefrontal cortex. AB - The neurons with visual properties were found to be distributed widely in the dorsolateral area of the monkey prefrontal cortex. The visual neurons located in the lateral part of the cortical area represented the central region of the contralateral visual field, while the neurons in the medial part the periphery of the visual field. The medial cortical part also contained auditory neurons which responded maximally to a sound whose angle of incidence was lateral or posterolateral to the animal's head (peripheral region of the environmental space). The observations indicate that the prefrontal visual and auditory neurons of one hemisphere function together to obtain an information of the contralateral space around the animal. PMID- 4024466 TI - Cerebral cortical activity associated with the orientation of visual attention in the rhesus monkey. AB - Attentional mechanisms in the posterior parietal cortex and the frontal eye fields have been studied in the rhesus monkey. In each of these areas single neurons discharge in response to visual stimuli and the discharge is enhanced when the monkey makes a saccade to the stimulus. In the posterior parietal cortex this enhancement also occurs whenever the monkey attends to the target, regardless of the movement or nonmovement that the monkey might make. Conversely, neurons in the frontal eye fields give enhanced responses only before saccades, and some discharge before purposive saccades made to remembered targets, with no overt current visual guidance. Some cells in the frontal eye fields also anticipate the onset of predictable saccades. PMID- 4024467 TI - On the detection of Gabor signals and discrimination of Gabor textures. AB - We have explored the detection and discrimination of Gabor signals in two different paradigms in order to determine the signals' relative importance for spatial vision. In the first experiment we determined the "detection efficiency" of five such signals presented in isolation, and our results support the conclusion that, for optimal detection, the Gaussian profile should only span (to 1/e decay values) approximately two cycles. In three subsequent experiments we have observed the discriminability of textures composed of such signals over a range of spatial frequencies, Gaussian windows and orientation differences. Our results are consistent with the detection data only insofar as the discrimination thresholds vary in a predictable way with the Gaussian window parameters. Finally, we have determined the degree to which texture discrimination, in terms of differences in both orientation and spatial frequency, can be predicted from the independent manipulations of both codes within a given Gaussian window size. PMID- 4024468 TI - A motion aftereffect from an isoluminant stimulus. AB - We investigate whether a motion aftereffect (MAE) can be induced by an isoluminant stimulus which contains colour contrast but no luminance contrast. We created a red/green chromatic stimulus, composed of red and green monochromatic grating added in antiphase, and corrected for the chromatic aberrations of the eye. We varied the ratio of the red to green luminances in the stimulus and found that there is no luminance ratio at which the MAE disappears. The results suggest that isoluminant stimuli can induce a MAE which is as great and sometimes greater than that induced by luminance contrast. PMID- 4024469 TI - Positional acuity with chromatic stimuli. AB - Theoretical reasons are presented for expecting a high precision spatial acuity task (vernier acuity) to be more difficult with an equiluminous stimulus than with stimuli containing luminance cues. This prediction was verified in Experiment 1. In a second experiment, it was shown that the result of the first experiment could not be explained by reduced detectability of the equiluminous target bar. We explain these results by the conflicting demands of chromatic and spatial differencing within a single mechanism, and propose that this also explains the similarities between long and medium wavelength cones in their spectral sensitivities. PMID- 4024470 TI - Origin of the electroretinogram in the intact macaque eye--I. Principal component analysis. AB - Responses to 400 msec flashes of white light were recorded at various depths in the retina of the intact macaque eye. A statistical technique, principal component analysis (PCA), was used to isolate independent components from the LERG, using the changing contribution of a cell's response to the LERG with retinal depth. Two approaches were evaluated: first, PCA was performed on the complete LERG waveforms and, second, on small sections of the LERG. The first method yielded a component strongly resembling the receptor response, apart from some inconsistencies in the proximal layers, and a component in which the b-wave was the most prominent feature, but which still contained some other responses. Hence, the components were not suitable to describe the LERG in terms of responses of specific cell types. The second method uses PCA to determine whether or not the potential change within a small time window is accounted for by a single component. This method, which essentially uses the knowledge that different cell types respond with different delay times, yielded three components. These were identified as the receptor component, the b-wave and the d.c.-component. The voltage-depth profiles of these components were assessed. PMID- 4024471 TI - Origin of the electroretinogram in the intact macaque eye--II. Current source density analysis. AB - Local electroretinograms (LERGs), evoked by 400 msec flashes of white light, were recorded as a function of retinal depth with a microelectrode in the intact eye of a macaque monkey. Retinal resistivity was measured as the potential difference between the tips of a bipolar microelectrode, resulting from a 300 msec current pulse which was passed through the retina. From the light evoked potentials and the resistivity the local currents in the retina were calculated. Current sources and sinks were localised for three LERG components. The receptor component had a current source in the outer segments (90% depth) and a sink in the ONL (70% depth). Both the b-wave and the d.c.-component had a source around 40% depth and a sink around 70% depth. The distribution of b-wave sources and sinks in primate seems to deviate from that in lower species, since no large current source is found in the most proximal layers. PMID- 4024472 TI - Local regulation of luminance gain. AB - Contrast sensitivity was measured for sinusoidal gratings sampled by compressing luminance into a variable number of sample bars. This procedure does not affect the amplitude or mean luminance of the grating, but does increase the local luminance of the sample bars: the fewer the bars, the more luminous they are. It was found that sensitivity increased with bars per cycle, particularly at low spatial frequencies. Further experiments, in which the local luminance of the sampling bars (but not the average luminance of the grating) was varied by addition of veiling glare showed that contrast sensitivity varied inversely with local bar luminance (a Weber type relationship). We interpret the results as evidence of local gain control under conditions where average luminance, and hence mean photon flux, does not vary. Calculations based on variation of sensitivity with spatial frequency suggest that gain control can be very localized, with receptive fields of Gaussian space constant of 0.5' arc. The relevance of these results to modern psychophysical concepts, including the definition of contrast is discussed. PMID- 4024473 TI - Neural interactions of two moving patterns in the direction and orientation domain in the complex cells of cat's visual cortex. AB - An examination was made of the responses of complex cells in cat's striate cortex to a textured (nonoriented) stimulus moving in the preferred direction, superimposed upon either a textured or a grating stimulus (oriented) that was moved in different directions. The cell discharges elicited by the textured stimulus moving in the preferred direction were reduced by the textured stimulus moving in nonpreferred directions, and increased when moved in the preferred direction. A grating moving in nonpreferred directions showed similar inhibitory effects on the responses to a textured stimulus moving in the preferred direction. Neural processing for directional movement is, therefore, affected by other neural processing for directional movement, and still more by that for orientation. PMID- 4024474 TI - Effects of contrast, orientation and binocularity in the pattern evoked potential. AB - Monocular and binocular visual evoked potentials were studied as a function of modulation depth (contrast) of a counterphase sinusoidal grating stimulus. A range of spatial and temporal frequencies of stimulation were used. The contrast functions showed many different forms, and were in some cases nonmonotonic. The binocular response usually had a steeper slope than the monocular response. Extrapolating the slope to the zero intercept gave electrophysiological thresholds which did not correspond with psychophysical threshold at any spatial or temporal frequency used. The binocular response was reduced to the monocular level when the orientation difference between the two eyes exceeded about 20 degrees. The data show that the pattern evoked potential is highly specific to many stimulus variables. PMID- 4024475 TI - A photoproduct with 13-cis retinal generated by irradiation with violet light in the octopus retina. AB - The photoconversion between rhodopsin (R) and metarhodopsin (MR) was investigated in the retina of Octopus ocellatus by measurements of the fast photovoltage (FPV) in conjunction with high pressure liquid chromatography (HPLC). Following conversion of most of R to MR by short-term exposure to an intense violet light, a large vitreous negative FPV due to photon absorption by MR was observed with an orange test flash. By continuing the exposure to the same violet light, however, the negative FPV became very small, though long-term irradiation with blue-green light produced a recovery. With the violet light exposure a substance other than R and MR is produced, which hardly contributes to FPV generation. Analysis of retinal isomers with HPLC show that such an exposure produces a substance with 13 cis retinal as its chromophore and that it was significantly reduced after exposure to blue-green light. PMID- 4024476 TI - The development of visual acuity in very young kittens. A study with forced choice preferential looking. AB - The development of visual acuity was studied longitudinally in young kittens, using a modification of the forced-choice preferential looking method (FPL) devised by Teller et al. [Vision Res. 14, 1433-1439 (1974)] for human infants. Acuity, defined as the spatial frequency which yields 70% correct responses by a naive observer, shows a 16-fold increase between 2 and 10 weeks of age. At comparable ages, acuity evaluated by this method falls short of the acuity values obtained with the mumping stand or with electrophysiological methods. FPL acuity estimated with a more lenient criterion (58%) comes close to the resolution of the highest-resolving single cells in the striate cortex. These results suggest that the preferential looking procedure provides a method that can be used in kittens over a wide age range, including ages at which it is impossible to use the jumping stand method. PMID- 4024477 TI - Reconstruction of neural control signals for saccades based on an inverse method. AB - The failure to obtain realistic saccadic velocity profiles, in earlier simulation studies using a linear oculomotor plant model and a stylized pulse-step input, has led to the development of quite complex plant models. The stylized-input assumption has later been shown to be unrealistic: it is known now that the pulse has a smooth shape in which the decay period is longer than the rising edge. To explore the applicability of linear models without imposing a priori constraints on the shape of the control signal, we have used Fourier deconvolution for reconstructing the neural-control signal. From the results obtained with this inverse method, we conclude that it is not necessary to use a complicated model in order to obtain realistic saccade velocity profiles. Furthermore, the results illustrate clearly that a second order linear plant model necessitates active braking at the input in order to explain the occurrence of short-lasting saccades. PMID- 4024478 TI - Eccentricity-dependent scaling of the limits for short-range apparent motion perception. AB - The ability to report the direction of apparent motion when an array of random dots is displaced fails when the displacement exceeds a limiting value (dmax). We find that dmax increases rapidly with retinal eccentricity, in a manner different from spatial measures such as acuity which are believed to depend on the "magnification factor" of projection to area 17. The minimum displacement giving detectable motion (dmin) shows a shallower increase with eccentricity which is more compatible with the variation of cortical magnification. The dependence of apparent motion on the timing variables (exposure duration, inter-stimulus interval) changes negligibly with eccentricity. Consequently the dynamic range and the upper limit of detectable velocities increases greatly with eccentricity. The increase of dmax with eccentricity means that the perception of apparent motion will show an approximate invariance with display scale, even though dmax has a locally fixed value depending on receptive field structure. PMID- 4024479 TI - Visual thresholds for shearing motion in monkey and man. AB - A reaction-time task was used to determine the visual motion thresholds in humans and in macaque monkeys for sinusoidally modulated shearing motion of a random dot display. It was found that humans and macaques were very similar in their spatial frequency sensitivity profiles for shearing motion. These profiles were of a U shape for all human and monkey subjects tested. Temporal frequency, varied over a wide range, did not influence the shape of the spatial frequency sensitivity curve, but only the threshold amplitudes. The above results held both for single and multiple temporal cycles of shearing motion. Previous reports for the human, using these same shearing motion stimuli, indicated no increase in threshold at the lower spatial frequencies. The reason for this discrepancy is that thresholds in the previous studies were not determined at a low enough spatial frequency to see clearly this increase in thresholds. Because of the striking similarity of the data for man and macaque, it is suggested that similar neural mechanisms underly the shearing motion sensitivity of the two species. PMID- 4024481 TI - Spectral sensitivity of the freshwater turtle Pseudemys scripta elegans: evidence for the filter-effect of colored oil droplets. AB - Spectral sensitivity was measured in the light adapted state for two individuals (S1 and S2) of Pseudemys scripta elegans using a behavioral training technique. The curves have three pronounced maxima at 450 nm, at 570 nm (S1) or 540 nm (S2), and at 640 nm. The spectral sensitivity functions can be described by the over envelope of the effective cone sensitivity functions which are determined by the absorption spectra of the cone photopigments (lambda max at 450, 518 and 620 nm) and by the filter properties of the colored oil droplets. PMID- 4024480 TI - Tritan discriminations by 1- and 2-month-old human infants. AB - The capacity of 1- and 2-month-old infants to make a tritan discrimination between a 4 degree, 416 nm test field and a 547 nm surround was tested by means of the forced-choice preferential looking technique. Most of the 2-month-olds and the other 1-month-olds made the tritan discrimination and must therefore have functional SWS cones. Most of the youngest 1-month-olds failed to make the tritan discrimination and therefore either do not encode or do not preserve the information ordinarily encoded by SWS cones. The implications of these data and the prior data of Hamer et al. [Vision Res. 22, 575-587 (1982)] are discussed in relation to color theory. PMID- 4024482 TI - Beyond the displacement limit: an analysis of short-range processes in apparent motion. AB - If a circle of random dots is presented in two successive displays in which the second is rotated in relation to the first, then observers are able to accurately discriminate the direction of apparent rotation as long as the rotation is small. Rotations beyond this short-range apparent motion can produce the impression of motion in the reverse direction. The performance in identifying the direction of rotation further depends on the eccentricity of stimulation and the density of the random dots. Simulations of the experiments using the Marr and Ullman model of motion detection are in good quantitative agreement with the data except for low dot density patterns and large displacements. In these situations perception seems to be dominated by the operation of long-range processes. PMID- 4024483 TI - Latency dependence of colour-based target vs nontarget discrimination by the saccadic system. AB - First saccade responses to sudden presentations of a target/nontarget stimulus consisting of green and red spots of light have been investigated. This paradigm, which avoids certain ambiguities present in earlier experiments with identical double stimuli, leads to remarkably similar conclusions. We found, again, that the saccadic system had short-latency compromising responses (averaging response mode) when the stimulus pair had a modest direction difference (delta phi). When delta phi was enlarged, first saccades were either directed near the green or the red spot (bistable response mode). In a second series of experiments different instructions, emphasizing either speed or accuracy of response, have been given to investigate the relation between saccade accuracy and latency. It appears that, independent of instruction, there is a fixed relation between saccade metrics and latency. The only way to avoid errors, such as averaging responses, is to delay the saccade. Hypothetical mechanisms underlying this relation are discussed against recent neurophysiological studies. PMID- 4024484 TI - The scotopic visibility curve and cone intrusion. AB - The scotopic visibility curves of two observers have been measured by determining their absolute thresholds for monochromatic lights and by direct comparison matching just above the threshold, in a 10 degree field with its centre 15 degrees above the fixation point. The results were all similar to the CIE scotopic curve. However, the threshold results in the long-wave part of the spectrum could be considerably modified by subliminal red and green lights. This is consistent with Drum's observations of sub-additivity at threshold. Above threshold, supra-additivity was obtained. A scotopic curve is evidently a non linear combination of rod and cone responses which varies with the conditions of observation. PMID- 4024485 TI - Pattern electroretinogram: use of noncorneal skin electrodes. AB - Pattern electroretinograms (ERGs) were recorded in three adults by a noncorneal electrode technique: silver-silver chloride skin electrodes attached to the inferior orbit of the left eye while the subject monocularly viewed a high contrast checker-board that reversed in contrast at a rate of 10 Hz. Recordings revealed pattern ERGs with an average amplitude of 1.5 microV. In addition, pattern ERGs were recorded as a function of spatial frequency and contrast of a square-wave grating. The results showed that an increase in spatial frequency or contrast yielded an increase in the amplitude of the pattern ERG. The results demonstrate that the pattern ERG can be recorded with a noncorneal electrode technique and that the noncorneal electrode technique is sensitive to changes in retinal function. Finally, it is demonstrated that the pattern ERG can transfer between the eyes such that the pattern ERG from a viewing eye can be recorded from an electrode placed below an occluded eye. PMID- 4024486 TI - A Maxwellian-view optometer suitable for electrophysiological and psychophysical research. PMID- 4024487 TI - [Clinical significance of radionuclide ventriculography in patients with myocardial infarct]. PMID- 4024488 TI - [Does intracoronary thrombolytic therapy in myocardial infarct improve left ventricular function?]. PMID- 4024489 TI - [Systemic thrombolysis in acute myocardial infarct]. PMID- 4024490 TI - [Renal osteopathy in long-term dialysis therapy--comparison of the alkaline phosphatase isoenzyme in bone with histologic findings]. PMID- 4024491 TI - [Intestinal absorption of calcium: physiological values and results in osteopathy]. PMID- 4024492 TI - [Lipid metabolism in relatives of diabetics]. PMID- 4024493 TI - [Index of peripheral thyroid effects in units responding to total serum thyroxine]. PMID- 4024494 TI - [General characteristics of extra-articular manifestations of rheumatoid arthritis]. PMID- 4024495 TI - [The reticulohistiocytic system and amyloid in the pathologico- anatomic picture in rheumatoid arthritis]. PMID- 4024496 TI - [Pathologico-anatomic findings in the kidneys and liver in rheumatoid arthritis]. PMID- 4024497 TI - [Possibilities of surgical treatment of pathologic fractures of the femoral neck]. PMID- 4024498 TI - [The effect of artificial air ionization on the number of bacteria in the air in a bacteriology laboratory]. PMID- 4024499 TI - [The activity of an ambulatory care facility in a military garrison]. PMID- 4024500 TI - [Our approach and position on the cessation of anti-epileptic therapy in soldiers admitted for observation for the verification of epilepsy]. PMID- 4024501 TI - [Fibronectin]. PMID- 4024502 TI - [Bromocriptine and Parkinson's disease]. PMID- 4024503 TI - [Primary leiomyosarcoma of the lung]. PMID- 4024504 TI - [Primary surgical care of soft-tissue injuries caused by bullets from modern military rifles in an animal experiment]. PMID- 4024505 TI - [Total occlusion of the main branch of the left coronary artery]. PMID- 4024506 TI - [Diagnostic significance of increased lung transparency in pulmonary thromboembolism]. PMID- 4024507 TI - [Aspects of preparation for work by the Yugoslav Blood Transfusion Service in a war of national defense]. PMID- 4024508 TI - [Modification of Wilson's osteotomy in the treatment of hallux valgus]. PMID- 4024509 TI - [Practical significance of the more common congenital anatomic variations of coronary arteries]. PMID- 4024510 TI - [Prodromal symptoms in patients with acute myocardial infarct]. PMID- 4024511 TI - [Penetration of radioactive dust through the skin]. PMID- 4024512 TI - [Yersinia enterocolitica. Study of its pathogenic characteristics]. PMID- 4024513 TI - [Treatment of gonorrheal urethritis with a single dose of penicillin in combination with probenecid]. PMID- 4024514 TI - [Several years' experience in the treatment of snake bites]. PMID- 4024515 TI - [Determination of ethylmorphine chloride, pilocarpine chloride and tetracaine chloride in drops and ointments for the eye]. PMID- 4024516 TI - [Radioisotope angiography and scintigraphy of the brain. Indications and differential diagnosis]. PMID- 4024517 TI - [Ultraviolet rays and occupational exposure]. PMID- 4024518 TI - [Report of a patient with liver angioma, tubular adenoma and a kidney cyst]. PMID- 4024519 TI - [Reiter's disease]. PMID- 4024520 TI - [Changes in parathyroid hormone levels during the treatment of fractures of long tubular bones using the Ilizarov method]. AB - Content of parathyroid hormone in blood plasma was studied in the course os treatment of 62 patients with fractures of crus bones. Alterations in the hormone content, depending on the type of trauma, were observed: the most severe injures caused the most distinct alterations. Maximal increase in the hormone content were observed during the initial period of the treatment, contributing to lysis of bone fragments and to formation of bone organic matrix. Decrease in the parathyroid hormone content coincided with complete consolidation of bone fragments. Content of the hormone was normalized within 35-42 days. PMID- 4024521 TI - [Effect of alcohol on the functional characteristics of the internal organs]. AB - Effects of alcohol on tissue respiration were studied in mice in vivo. Alcohol decreased the efficiency of energy metabolism, affecting the working capacity. Possible mechanisms of impairment of tissue respiration in presence of alcohol are discussed. Effect of a single-day consumption of alcohol at high doses on functional characteristics of the vitally important tissues was studied in track and field athletes using the methods of auriculodiagnostics. Tissue dependent type of the alcohol intoxication as well as its long-term effects were shown. PMID- 4024522 TI - [Radioimmunologic determination of androstenedione and the effect of physical training on its levels in human blood and saliva]. AB - A radioimmunoassay (RIA) of androstenedione in biological fluids was developed. The sensitivity of the method was 30 pg/ml. The efficiency of the standard detection in blood and saliva was 98.2%. The intra- and interassay variations were 5.6% and 12,7%, respectively. Specificity pf the antiserum was determined in cross reactions using 17 steroids. The specificity depended upon the method used, the duration of immunization and the quantity of the antigen. Mathematic methods were used for definition of optimal values of the main parameters and conditions for RIA. 60 different regimes were investigated. The influence of regular physical exercises on androstenedione content in blood and saliva was investigated in 100 athletes. Physical exercises increased androstenedione concentration in men and women blood and saliva. Concentration of androstenedione was increased 1.3- and 2.2-fold in men blood and saliva, respectively, the concentration of androstenedione was increased 1.6-fold in women blood. PMID- 4024523 TI - [Biochemical changes in the rat immunocompetent organs during oxythiamine involution of the thymus]. AB - Oxythiamine injections to rats (400 mg/kg of body mass, subcutaneously, 2 injections with 48 hrs interval) caused 70% involution of thymus within 72 hrs after the first injection. The transketolase activity was inhibited by 70%, that of glucose-6-phosphate dehydrogenase by 15%, while the aldopentose level was decreased by 56% in the thymus. Inhibition of DNA and RNA synthesis was directly dependent on the dose and duration of the oxythiamine effect on the gland. Reduction of transketolase activity was accompanied by an adaptive; increase in glucose-6-phosphate dehydrogenase activity as well as by a decrease in levels of nicotinamide coenzymes (NAD, NADP) in spleen. PMID- 4024524 TI - [Immunochemical and physico-chemical characteristics of lactoferrin in human body fluids]. AB - It is proved that lactoferrins of different human body fluids (sperm, saliva, milk, tears, urine, bile, sweat, liquor, lymph, blood serum) are immunochemically identical. The lactoferrin is purified from milk, saliva and sperm and the identity of physical and chemical properties of lactoferrins of various origins is proved. The quantitative estimation of the contents of this protein in normal body fluids is given. It is detected the dependence of this protein' electrophoretic mobility and isoelectric point of degree of iron saturation. It is found that lactoferrin is capable to form complexes with esterase. PMID- 4024525 TI - [Various reasons for changes in the phospholipid composition of high density lipoproteins in hypoalphacholesterolemia]. AB - In men without any symptoms of ischemic heart disease, living in two different geographical zones (Moscow and Chuckchee land) low level of high density lipoprotein (HDL) cholesterol was accompanied by alterations in phospholipid composition of HDL2 and HDL3: decrease in the ration of lecithin and increase in sphingomyelin and kephalin content. The alteration in the phospholipid composition of these two HDL subclasses occurred simultaneously with changes in fatty acid composition of HDL lecithin: decrease in the ratio of linoleic acid as well as in stearic and arachidonic or eucosepentaenic acids. At the same time, phospholipid composition of the HDL subclasses was dissimilar in men and women without any symptoms of ischemic heart disease. Role of alterations in the fatty acid composition of phosphatide acid as well as effect of hormones on alterations in the phospholipid composition of HDL in hypoalphacholesterolemia are discussed. PMID- 4024526 TI - [The role of changes in the antioxidative activity and phospholipid composition of the rat liver in the mechanism of phenazepam action on the liver and the protective effect of talamonal]. AB - Phenazepame exhibited properties of prooxidant in a model system of oleic acid methyl ester oxidation. After single intraperitoneal administration of phenazepame (5 mg/kg) the antioxidative activity (AOA) of rat liver lipids was decreased, correlating with level of histidase and urokinase activity in blood plasma indicating the liver tissue injury. Distinct alterations in the relative content of liver phospholipids were also noted. A phase type of alterations was observed in the content of these phospholipids as well as in the ratio phosphatidyl choline/phosphatidyl ethanolamine; at the same time, the phospholipid ratio was altered simultaneously with the alterations of the enzymatic activities in blood. After administration of the antioxidant, which normalized the AOA level and the phospholipid composition, activities of histidase and urokinase were markedly decreased in blood. The neuroleptanalgetic drug thalamonale, protecting liver tissue against the impairments, normalized the AOA level and the phospholipid composition. Thus, alterations in AOA and in the phospholipid composition reflected distinctly the unfavourable effect of phenazepame as well as the protecting action of thalamonale on liver tissue. PMID- 4024528 TI - [Thermostabilization of glutamin(asparagin)ase from Pseudomonas aurantica BKMB 548]. AB - In studies on kinetics of thermoinactivation of glutaminase (asparaginase) from Ps. arantiaca BKMB-548 at 50 degrees and pH 7.0 in presence or in absence of L glutamate the enzyme inactivation was found to obey the first order equation. Both the glutaminase and asparaginase activities decreased at a similar rate. L Glutamate stabilized the enzyme due to direct interaction with its molecule. Stability of the complex formed was evaluated quantitatively. L-Glutamate reacted apparently with a specific site on the surface of the enzyme molecule; Kdiss was 0.42 +/- 0.03 mM at pH 7.0 and 50 degrees. No cooperative effect was found. L Aspartate protected the enzyme completely; stabilizing effects of L-cysteine, L serine and glycine were similar to the effect of L-glutamate (94%, 84%, 83% and 82%, respectively). At the same time, glutarate, succinate, alpha-ketobutyrate, alpha-ketoglutarate, gamma-aminobutyrate and N-benzoyl glutamate did not exhibit the stabilization effect. The data obtained suggest that the high stabilizing effect might exhibit only the substances containing simultaneously free alpha-NH2 and alpha-COOH groups in a molecule, whereas presence of COOH groups at beta--or gamma-carbon atoms was not essential for the stabilizing effect. PMID- 4024527 TI - [Carbohydrate metabolism of the skeletal muscle of the ischemic extremity in acute and chronic occlusion of the major arteries in man]. AB - Activation of glycolysis and glycogenolysis as well as stimulation of the pentosephosphate pathway of glucose oxidation occurred in skeletal muscle of the ischemized legs of patients with occlusive impairments of main arteries. PMID- 4024529 TI - [Antithrombin III activity in relation to multiple administration of various doses of heparin to normal animals]. AB - Heparin affected the content of antithrombin III and the thrombin time of blood plasma coagulation depending on the dose of the anticoagulant administered (eight intravenous administrations at single doses of 225, 150, 75, 37 or 18 IU/kg of body mass of healthy rats). High doses of heparin decreased more distinctly the content of antithrombin III as compared with low doses. 8 intravenous infusions of small doses of heparin (37 IU/kg) as well as intramuscular administration of the anticoagulant (10 injections) at a dose of 225 IU/kg caused a compensatory increase in content of antithrombin III. After 30 intramuscular administrations the compensatory reaction of antithrombin III disappeared. In this case the content of antithrombin III and the thrombin time of blood plasma coagulation exhibited stability towards the anticoagulant effect. PMID- 4024530 TI - [Iron-containing blood proteins in poisoning by polyamide compounds]. AB - Chronic treatment (by means of inhalation) of rats with polyamide substances was accompanied by destabilization of erythrocyte membranes causing penetration of hemoglobin into blood serum. Electrophoresis of blood serum proteins in 7.5% polyacrylamide gel exhibited appearance of additional hemoglobin fractions electrophoretic mobility of which corresponded to the Ist and 4th fractions of erythrocyte hemoglobins. Estimation of hemoglobin composition in blood serum might be used for diagnostics of polyamide intoxication. PMID- 4024531 TI - [Polymerization of Straub's actin in patients with myocardial infarction and in experimental occlusion of coronary arteries]. AB - Rates of actin polymerization and of contractility of myocardial glycerinated fibers (the myofibrillar contractile system) were found to be decreased in patients with myocardium infarction and in experimental heart ischemia. The phenomena were noted within the earliest period under study (I hr after development of ischemia). Causes of the decrease in the rates of actin polymerization and of the myofibrillar contractility did not involve hypoxia and acidosis. They were observed in non-ischemic and non-infarcted zones of left ventricles and in non-impaired right ventricles. The data obtained suggest that alterations in physico-chemical properties of actin (the main protein of thin myofilament) leading the decrease in the contractile functions, were responsible for acute failure of heart muscle in ischemia and infarction. PMID- 4024532 TI - [Mechanism of action of sodium oxybutyrate in experimental myocardial infarction]. AB - Effect of sodium hydroxybutyrate on lipid metabolism was studied in experimental infarction of rabbit myocardium. Administration of 80 mg of sodium hydroxybutyrate per kg of body mass caused a decrease of free fatty acids content in the infarction zone, in surrounding zones and in blood. Treatment of the experimental animals with sodium hydroxybutyrate normalized distinctly the phospholipid composition of the ischemized myocardium. Content of phosphatidyl choline, phosphatidyl ethanolamine and cardiolipine was increased in the infarction zone and in surrounding zones of myocardium. Concentration of lysolecithines was decreased in the both zone studied. In the animals treated with sodium hydroxy butyrate after the infarction output of myocardial creatine kinase into circulation was decreased. PMID- 4024533 TI - [Mechanism of impairment of energy metabolism in respiratory muscles in experimental botulism]. AB - Phase alterations in content of adenylic nucleotides were observed in muscular and nervous tissues in dynamics of botulinic intoxication in rats. Experiments with administration of 4-aminopyridine and alpha-tocopherol showed that a decreased rate of mediator liberation in cholinergic synapses and activation of lipid peroxidation were apparently responsible for impairments in energy metabolism. PMID- 4024534 TI - [Blood levels of glycosylated hemoglobin and ATP in diabetes mellitus in children]. AB - To elucidate possible role of alterations in levels of glycosylated hemoglobin and ATP of blood in pathogenesis of diabetic impairments, 29 children with insulin-dependent diabetes mellitus were studied. In these children the blood content of the glycosylated hemoglobin was distinctly increased simultaneously with a decrease in ATP level. The alterations were especially distinct in the children the parents of which suffered from ischemic heart disease, myocardial infarction, insult, hypertension, diabetes mellitus. Development of diabetes mellitus in these children was characterized by the most severe manifestations (especially frequent and severe diabetic lesions, distinct decreases in secretion of insulin and in efficiency of the hormone). A hypothesis is discussed on possible importance of accelerated glycosylation of proteins and of a decrease in ATP synthesis for development of diabetic lesions. PMID- 4024535 TI - [Clinical role of lipid metabolism indices in the plasma and erythrocytes in progressive muscular dystrophies]. AB - Patterns of lipid metabolism were studied in blood plasma and erythrocytes of patients with various forms of hereditary myopathies (Duchenn disease, Bekker Kiner disease, Erba-Roth disease, Landuzy-Dejerin disease, Sharko-Mary neural amyotrophy). These diseases were characterized by a number of common patterns: deficiency of phospholipids, specific alterations in properties of lipoproteins and in content of cholesterol. In the Duchenn disease specific alterations typical for each step of the disease were shown. These alterations might be of prognostic significance for evaluation of the rate of myodystrophy development. PMID- 4024536 TI - [Fatty acid composition and lipid peroxidation in brain microsomes of albino rats with alloxan diabetes]. AB - Fatty acid composition and lipid peroxidation in rat brain microsomes were studied under conditions of alloxan diabetes. The data obtained indicate significant differences in the content of unsaturated fatty acids and also a slight activation of lipid peroxidation in the pathological state studied. PMID- 4024537 TI - [Comparative study of silylated heparin and sodium heparinate]. AB - Trimethylsilyl heparin formed a complex with fibrinogen, caused anticoagulation and antipolymerization effects on fibrin-monomer as well as exhibited nonenzymatic fibrinolytic activity towards unstabilized fibrin. PMID- 4024539 TI - [Evaluation of the degree of endogenous intoxication in oncological patients]. AB - The paper is concerned with an evaluation of leucocyte index of intoxication, neutrophile/lymphocyte ratio and nuclear index in 55 patients with ovarian malignancies and 74 cases of stage IV lung cancer. Also, the said indexes were followed in 68 cases of gynecologic malignancies and 62 cases of lung cancer after radical surgery. Lymphocytic index of intoxication proved to be instrumental in the evaluation of endogenous intoxication in stage IV lung cancer and ovarian tumors before and after surgery. PMID- 4024538 TI - [Comparison of the effect of homologous and heterologous albumin on the activity of lipoprotein lipase and liver triglyceride lipase in rabbit plasma]. AB - Changes in the activity of blood plasma lipoprotein lipase (EC 3.1.1.34, LPL and hepatic triacylglycerol lipase EC 3.1.1.3, H-TGL) were studied in rabbits injected intravenously by homologous and heterologous albumins (bovine, fraction Y, Sigma, BSA) alone and in combination with heparin. Rabbit albumin enhanced the effect of heparin on the LPL activity, while heterologous protein, to the contrary, diminished it. The in vitro experiments showed that BSA caused a more distinct effect on the LPL activity as compared with that of rabbit albumin. The activity of H-TGL was not significantly altered under the influence of both proteins. PMID- 4024540 TI - [Surgical treatment of cancer of the proximal section of the stomach]. AB - The report deals with an evaluation of the results of 430 radical operations for cancer of the proximal part of the stomach. The lethality rates following proximal resection were 16.8% and 13.1% after gastrectomy. Neither splenectomy nor marginal resection of the liver resulted in a significant increase in postoperative mortality which, however, soared up by as much as 50% after radical surgery involving the resection of the pancreas. PMID- 4024541 TI - [Carcinoid of the trachea simulating bronchial asthma (1 case)]. PMID- 4024542 TI - [Trace elements in polymorphic adenomas of the parotid salivary glands]. PMID- 4024543 TI - [Pneumatosis cystoides intestinalis simulating a tumor of the large intestine (1 case)]. PMID- 4024544 TI - [Comparison of the tabular survival indices of 2 prognostically heterogeneous patient groups]. PMID- 4024545 TI - [Resistance to the inhibitory effect of dexamethasone in brain tumor patients]. AB - Out of 24 patients with brain tumors, 22 proved to be resistant to inhibition by dexamethasone. There were no significant differences in the sensitivity to dexamethasone in three study groups established on the basis of the tumor site-to diencephalic structures distance. A relatively higher frequency of disturbances in dexamethasone inhibition in patients with brain tumors suggests grave disorders induced in glucocorticoid secretion regulation by chronic stress. PMID- 4024546 TI - [Intraoperative diagnosis of incipient stomach cancer]. AB - A combination procedure of surgical fibrogastroscopy was employed for diagnosis of incipient gastric carcinoma. It involved a routine examination of the mucosa, transillumination (examination in transmitted light) and endoscopy of the illuminated surgically-exposed stomach, with the endoscope's ligh being switched off. The study conducted in 24 patients with incipient carcinoma showed the effectiveness of the said diagnostic procedure in identifying foci of such lesions, their anatomic pattern as well as the extent of involvement of different layers of the stomach wall, submucosal and serous muscular layer. PMID- 4024547 TI - [Effect of an operation on the immunoreactivity indices, their postoperative dynamics and the effect of 3-HAA-antigen on these indices in patients with gastrointestinal tumors]. AB - The following parameters were studied in cases of gastrointestinal tumors: 3 hydroxyanthranilic acid (3-HAA)-antigen in blood serum; antibodies to 3-HAA antigen; immunoglobulins G, A and M (after Manchini); 3-HAA-antigen effect on blastogenic reaction of lymphocytes; 3-HAA-antigen effect on leucocyte migration; blood serum effect on cells producing antibodies to ram erythrocytes, and levels of T-lymphocytes and their subpopulations. The studies were conducted before operation, 4-6, 7 and more months after operation. Tumor removal as well as tumor recurrences and metastases were shown to have an effect on the first 4 parameters. 3-HAA-antigen stimulated the formation of specific antibodies, suppressed blastogenic reaction of lymphocytes but failed to affect leucocyte migration significantly. PMID- 4024548 TI - [Risk factors for the development of endometrial cancer in uterine myoma]. AB - It was shown that the risk for endometrial cancer development in uterine myoma increases 43-fold in cases of diabetes mellitus, hypertension and obesity, 20 fold in adnexitis, 15-fold in hyperplastic endometrial lesions and 9.8-fold in the multipara. PMID- 4024549 TI - [Effect of age on carcinogenesis in female rats induced by methyl (acetoxymethyl) nitrosamine]. AB - A single intraperitoneal injection of methyl-acetoxymethyl-nitrosamine produced tumors in 85.7% of 3 month-old female rats and in 62.5% of 14 month-old ones matched by 26.5% in controls. Intestinal tumors developed most frequently. Also, tumors of the pituitary, thyroid, breast, uterus as well as leukemia were detected. Multiple intestinal tumors were more frequent in the young age group (1.43 and 1.00), tumor-free interval in older animals being 217 days longer. Studies on DNA alkylation and repair were carried out using intraperitoneal injections of 14C-methyl-acetoxymethyl-nitrosamine. Young animals showed higher levels of methylpurines in organ tissues other than those of small intestine 3 hrs after treatment. The rate of methylpurine excretion in young rats was higher, too. However, liver tissue of old rats showed a higher rate of O6-methylguanine repair than that in younger ones. PMID- 4024550 TI - [DNA reparative synthesis in liver cell cultures from mice with various susceptibilities to spontaneous hepatic carcinogenesis]. AB - Ultra-violet radiation-induced unscheduled DNA synthesis in liver cell cultures from CBA, C57Bl/6j and AKR adult male mice was studied autoradiographically. Ultra-violet radiation (254 nm; 1.5-36 J/m2) triggered on an active unscheduled DNA synthesis in all cell cultures studied. The levels of unscheduled DNA synthesis in the liver cell nuclei of the spontaneous hepatocarcinogenesis susceptible strain (CBA) and relatively, resistant ones (C57Bl/6j and AKR) were similar. It is suggested that the susceptibility to hepatocarcinogenesis in different murine strains is determined by such parameters as DNA damage and repair (stage of initiation) as well as factors peculiar to the stage of promotion. PMID- 4024551 TI - [Identification of the transforming Ha-ras gene in human melanoma, neuroblastoma and breast cancer cells]. AB - Preparations of DNA isolated from malignant melanoma (Ja heterotransplant), neuroblastoma (L-AN-1 cell line) and breast cancer (SK-BR-3 cell line) induced a high incidence of transformation of recipient NIH 3T3 cells in two consecutive cycles of transfection. Transformed NIH 3T3 cells appeared to be highly tumorigenic in newborn BALB/c mice. The analysis of DNA samples isolated from primary and secondary NIH 3T3 transformants identified Alu-repetitive DNA sequences of human genome as well as additional sequences homologous to ras family oncogene. Transforming c-Ha-ras I gene was identified for the first time in NIH 3T3 cells transformed by preparations of DNA isolated from human malignant melanoma, neuroblastoma and breast cancer. PMID- 4024552 TI - [Immediate results of the surgical treatment of gynecologic neoplasm patients over 60]. AB - Surgery was carried out in 1,229 cases (346 (28.1%) aged 60 and older) at the gynecological department of the Dispensary in 1976-1983. The operability rate in the aged and old-age bracket was 55.2%. Malignancies were registered in 239 benign tumors--in 107 cases. 16 patients died (4.6%), thromboembolism of the lung artery being the most frequent cause of postoperative mortality. A combination of neuroleptanalgetics, barbiturates and nitrous oxide is recommended for anesthesia. PMID- 4024553 TI - [Action of unithiol on the toxic effect of antitumor preparations]. AB - The effect of unitiol treatment on the toxicity of dactinomycin, 5-fluorouracil, bleomycetin and vincristine was studied in CBA mice. Unitiol treatment was shown to decrease the acute toxicity of dactinomycin and involves a lower loss of body weight. Also, it reduced dactinomycin hemotoxicity which was assessed on the basis of leukocyte count in peripheral blood. Conversely, unitiol potentiated the acute toxic effect of 5-fluorouracil, bleomycetin and vincristine which was matched by body weight loss following treatment with cytostatic drugs. The results point to a wide range of the biological effects of unitiol. PMID- 4024554 TI - [Mechanisms of the effect of polyamines on the complex-forming ability of blood plasma ribonucleases]. AB - The study was concerned with the pathways of protein complexing in tumor growth. The effects of polyamines on blood plasma proteins and, particularly, on ribonuclease were investigated as a possible modifier of protein--protein interactions. In application of an ultrafiltration procedure, in vitro addition of polyamines to blood plasma imitated certain changes in plasma proteins which take place in tumor growth: filtrate showed a rise in the low molecular weight protein fraction, ribonuclease included. Peak concentrations of protein in filtrate were obtained virtually as soon as polyamines were added to incubation medium. The dissociating effect of polyamines was determined on the basis of the polyamine/protein ratio. Protein complexing was shown to be subject to the effects of both polyamines and products of their enzymatic oxidation. PMID- 4024555 TI - [An all-embracing concern for our successors in science]. PMID- 4024556 TI - [Use of the carcinoembryonic antigen in the gastric juice for diagnosing pretumorous stomach diseases]. AB - Radioimmunologic procedures were employed in comparing the levels of carcino embryonic antigen in the gastric juice, blood plasma and saliva in cases of stomach cancer, gastritis, polyposis and gastric ulcer. No correlation between the antigen levels in different biological fluids was established. It was found, however, that the assay of carcino-embryonic antigen level in gastric juice may be instrumental in detecting precancerous lesions of the stomach. PMID- 4024557 TI - [Rapid cytological diagnosis in cancer of the lung, stomach and esophagus]. AB - The results of 1,053 express cytological examinations carried out in 369 patients were assessed. The scope and limitations of the procedure as well as errors involved were analysed. It was found that express cytological examinations provide a means for adequate evaluation of the nature and extent of cancer pathology and are instrumental in working out effective schemes of surgical treatment. An intraoperative cytological examination of lymph nodes can substitute a histological one. PMID- 4024558 TI - [Factors affecting the occurrence of cancer relapses in the intrathoracic portion of the esophagus after radical treatment]. AB - The results of a retrospective clinico-statistical evaluation of the data on 35 cases of cancer of the thoracic part of the esophagus recurring after "radical" treatment pointed to the following factors responsible for relapse: tumor stage, level at which tumor is located and degree of local expansion. The latter factor seemed to be of paramount importance. PMID- 4024559 TI - [Clinico-morphological characteristics of background diseases in stage I stomach cancer]. AB - A study on alterations occurring in gastric mucosa in cases of stage I stomach cancer identified chronic gastritis involving gland atrophy of varying degree as the basic background feature, with intestinal metaplasia and dysplasia being common manifestations of precancerous lesion development. Malignant transformation of hyperplastic polyps and adenomas occurs in areas in which dysplasia of metaplastic epithelium tends to spread. Stomach cancer development from gastric ulcer seems unlikely. Morphological factors should be considered, when groups of high risk for stomach cancer development are identified among cases of chronic gastric diseases. PMID- 4024560 TI - [Variants of surgical methods for localized forms of breast cancer]. AB - An analysis of the data on 145 surgical cases of stage I and IIA breast cancer was undertaken. Organ-saving procedures were carried out in 22 cases. Five-year results of treatment of 55 cases were studied. Surgery is the most effective procedure of treatment of localized breast cancer. Organ-saving operations as the only treatment procedure should not be carried out onless certain prognostic factors are considered. PMID- 4024561 TI - [Possibilities in the conservative treatment of patients with early forms of uterine cancer]. AB - Organ-saving surgery was used in 134 patients with early cervical cancer (high amputation with a lancet-98 and cryotherapy-36 cases). The efficiency of the procedure was verified by morphological examination of samples obtained from the operation site at certain periods after primary treatment. The results of surgical treatment and hormonotherapy of early endometrial cancer (66 and 17 cases, respectively) are presented. Sparing methods may be used for treatment of early cancer of the uterus. Due to their application, menstrual, sexual and reproductive functions are preserved. PMID- 4024562 TI - [Factors affecting late treatment results with uterine choriocarcinoma patients]. AB - Factors influencing posttreatment survival of uterine choriocarcinoma patients were studied in 166 cases of histologically-verified tumor. Procedures for calculating indexes of actual survival as well as tabulated rates of 3- and 5 year survival are presented. A 3-year period of follow-up appeared to be sufficient for evaluation of prognosis. The following factors proved to be of the highest prognostic value: the outcome of preceding pregnancy, duration of latent and symptom periods, peripheral blood count, parametrial involvement, changes of chorionic gonadotropin level in the course of treatment, site of metastasis and cytostatic drugs used. PMID- 4024563 TI - [Sequence of using the components of combined treatment in stage III and IV ovarian cancer patients and late treatment results]. AB - The paper presents the results of a retrospective analysis of the data on 413 cases of stage III-IV epithelial malignancies of the ovaries. Application of the surgery+chemotherapy scheme for initial treatment secured better results than any other treatment modality. There was no correlation between survival, tumor stage and scheme of subsequent therapy. PMID- 4024564 TI - [Central nervous system lesions in leukemia in children]. AB - Initial morphologic manifestations of neuroleukemia consisted in tumor cell infiltration of the fat tissue of the epidural space (mainly, the lumbar region of the spine) and dura and pia mater spinalis. Leukemia infiltration of the central nervous system was due to tumor cell migration from the bone marrow via perivascular spaces. PMID- 4024565 TI - [Effect of the splenic cells of tumor-bearing mice on the allograft immune response]. AB - An earlier experimental model employing quantitative analysis of allotransplantation immune response in vivo and registration of the functional activity of immunoregulatory cells was used. It was established that syngeneic transfer of spleen cells from mice bearing 20-methylcholanthrene-induced tumors to normal intact mice modifies immune response to allogeneic cells. The effect of splenocytes was found to depend on the rate of tumor growth. Moreover, the method of syngeneic transfer (systemic application or local injection) of immunoregulatory cells appeared to be of great importance for the realization of suppressive or stimulative effect of splenocytes. Possible causes of changes in the extent and nature of the effect of lymphocytes from tumor-bearing mice on allotransplantation immune response in vivo are discussed. PMID- 4024566 TI - [Importance of the cyclophosphane administration regimen for its immunomodulating and antitumor effect in experimental chemotherapy]. AB - Cytological examinations and evaluation of the proliferative response of lymph node lymphocytes to T- and B-cell mitogens in vivo were carried out to identify the immunomodulating effect of cyclophosphamide (CP) versus the scheme of treatment. Using the system of adoptive transfer of splenic lymphocytes from experimental animals to intact syngeneic recipients, it was found that the scheme dependent differentiated effects of CP on the antigen-specific tumor-associated and nonspecific suppressive activity of spleen cells provides an important pathway of CP action on the organism. A relationship between CP immunomodulating effects and lymphocyte antitumor activity was demonstrated in experiments using diffusion chambers. PMID- 4024567 TI - [Effect of cyclophosphane on lipid peroxidation]. AB - Single and repeated treatment with toxic doses of cyclophosphamide was shown to activate peroxidation of lipids of myocardial, pulmonary, hepatic and renal cell membranes. An antioxidant-silymarin-inhibited the prooxidating effect of cyclophosphamide thus suggesting further studies of antioxidants as means for counteracting the adverse effects of cytostatic drugs. PMID- 4024568 TI - [Early diagnosis of hepatitis A]. PMID- 4024569 TI - [Clinical analysis of the causes of fatal outcome in infection]. PMID- 4024570 TI - [Soil properties and the etiology of ascariasis in humans]. PMID- 4024571 TI - [Utilization of emergency medical services by patients of retirement age]. PMID- 4024572 TI - [Experience in improving the effectiveness of the dispensarization of patients with primary glaucoma]. PMID- 4024573 TI - [Indicators of hemodynamics in patients with ischemic heart disease and the initial stage of cardiac insufficiency]. PMID- 4024574 TI - [Mechanism of the therapeutic effect of helium-neon laser in various cardiovascular diseases]. PMID- 4024575 TI - [Acute surgical diseases of the abdominal organs associated with myocardial infarction]. PMID- 4024576 TI - [Acute myocardial infarction in brothers with peptic ulcer]. PMID- 4024577 TI - [The renin-angiotensin system and central hemodynamics on borderline arterial hypertension]. PMID- 4024578 TI - [Use of nitrogen baths in the complex treatment of patients with hypertension]. PMID- 4024579 TI - [Characteristics of hemodynamics in the passive orthostatic test]. PMID- 4024581 TI - [Characteristics of the central hemodynamics and morphofunctional state of the myocardium in patients with nonspecific lung diseases]. PMID- 4024580 TI - [A case of successful correction of a complicated form of congenital aortic stenosis using bioprosthesis]. PMID- 4024582 TI - [Serum lysozyme levels in patients with pulmonary tuberculosis and chronic nonspecific lung diseases]. PMID- 4024583 TI - [Differential diagnosis of nonspecific pneumonia and infiltrative pulmonary tuberculosis]. PMID- 4024584 TI - [Determining the activity of pulmonary tuberculomas]. PMID- 4024585 TI - [A case of pulmonary adenomatosis]. PMID- 4024586 TI - [Anastomosis ligatures simulating recurrence of peptic ulcer]. PMID- 4024587 TI - [Morphofunctional changes in microvessels of the stomach and pancreas in early periods following selective vagotomy]. PMID- 4024588 TI - [Use of sodium succinate in patients with a history of myocardial infarction]. PMID- 4024590 TI - [Myeloma nephropathy]. PMID- 4024589 TI - [Enzyme activity and dynamics of blood levels of microelements during the complex treatment of chronic liver diseases]. PMID- 4024591 TI - [Copper and zinc levels in blood components in different body conditions]. PMID- 4024592 TI - [Significance of hypo- and areflexia of the cornea in the early diagnosis of disseminated sclerosis]. PMID- 4024593 TI - [Gnosis centers of speech and gesture]. PMID- 4024594 TI - [Sequelae of closed cranio-cerebral injuries in childhood]. PMID- 4024595 TI - [Ecological and hygienic problems of the development of nuclear energy]. PMID- 4024596 TI - [Possibility of using data on the manganese content of the hair of welders as an exposure test]. PMID- 4024597 TI - [Blood serotonin levels and urinary excretion of tryptamine in toxic hepatitis caused by fluoride compounds]. PMID- 4024598 TI - [Experimental substantiation of using immunomodulators of the phenylimidazothiazole type for the correction of secondary immunologic insufficiency caused by poliomyelitis virus]. PMID- 4024599 TI - [A case of trichinelliasis and food poisoning]. PMID- 4024600 TI - [Urinary catecholamines in normal-weight and overweight diabetics]. AB - The 24-h urine excretion of free, conjugated and total fraction of Dopa, dopamine, noradrenaline and adrenaline was studied in diabetics with normal weight and overweight. A tendency to lower excretion of adrenaline, noradrenaline and dopamine was established in diabetics with overweight as well as a tendency to reverse correlation between overweight and urine excretion of catecholamines. On the base of the so called synthesis and degradation coefficients, the possibility the changes established in the diabetics with overweight to be due to reduced synthesis of dopamine and noradrenaline is discussed. A presumption is presented about the possible causative relation between the reduction of catecholamine excretion and overweight in diabetics. PMID- 4024601 TI - [Erythrocyte enzymes in chronic kidney failure]. AB - Forty four patients with various degrees of chronic renal insufficiency (CRI) were studied. The activity of both dehydrogenases and pentosephosphate pathway (PPhP) in erythrocyte--glucose-6-phosphate dehydrogenase (G6PD), and 6 phosphogluconate dehydrogenase (6-PGD), as well as the activity of the main generating ATP-enzyme of glycolysis--pyruvate kinase (PK) was studied. The activity of the erythrocyte enzymes studied grows with the intensification of renal insufficiency, particularly manifested in G6PD and PK. PMID- 4024602 TI - [Invasive aspergillosis in patients who died from acute leukemia]. AB - The necropsy material with acute leukosis (166 deceased) was studied in order to establish the incidence of invasive aspergillosis. It was established in 16 of the deceased (9,64%): aspergillosis pneumonia--in 5 cases, aspergillosis sepsis- in II, with invasion of lungs, brain, spleen, liver, myocardium and other organs. Clinically aspergillosis was not distinguished. Continuous septic temperature, not influenced by antibiotic therapy should draw the attention to the presence of aspergillosis. The factors, preconditioning aspergillosis infection are stressed upon: immune-suppressive treatment in acute leukosis, granulocytopenia, continuous preceding antibiotic therapy, etc. The difficulties in the clinical differentiation of the infection are emphasized. With a view to the high incidence and lethality of aspergillosis in acute leukosis, the introduction of modern diagnostic methods and treatment are underlined to be necessary. PMID- 4024603 TI - [Acute kidney failure and acute toxic cholestatic hepatitis caused by a large amount of analgin]. PMID- 4024604 TI - [Acute allopurinol (milurit) poisoning]. AB - A patient with gout and schizophrenia is described who during a schizophrenic paroxysm with paranoid-hypochondriac-hallucinatory syndrome attempted to commit suicide and took 200 tablets milurit (20 g). He developed the picture of acute intoxication with nausea, vomiting, profuse diarrhea, abdominal pain, flushing, temperature, collapse manifestations, hepatomegaly, direct hyperbilirubinemia, elevated transaminase, leukopenia, accelerated ESR. After reanimation and infusion therapy, the patient recovered within 4 days and 2 weeks later all blood indices reached the limits of the norm. PMID- 4024605 TI - [Ultrastructural mechanisms of the antacid effect of biomet in duodenal ulcer patients]. AB - Corpus gastric mucosa, obtained via repeated blind aspiration biopsy--before and after 10 day treatment with biomet--1 g daily, was electron microscopically studied in 10 patients with active duodenal ulcer. Before the treatment, the wall adjoining cells were with high hyperplasia of intracytoplasmatic tubules, which pressed in separate groups-packets the numerous mitochondria with data about hyper-reactivity, on the background of scarce or absent tubulo-vesicular structures. After a 10-day biomet treatment, the reduced area of intracytoplasmatic tubules of wall-adjoining cells is obvious as well as the recovery of tubulo vesicular structures. Often, in single patients, endocrine G cells were observed. With the intragastric pH-metry, however, performed in 2 of the patients, before and by 90 min after the intravenous administration of 200 mg tagamet--significantly elevated values of pH of gastric mucosa were established, positively correlating with the described ultrastructural changes in wall adjoining cells. The antacid effect of biomet, is very likely, realized via the mechanism of reduction of the surface of the secreting membrane structures, responsible for the production of hydrochloric acid by gastric mucosa. PMID- 4024606 TI - [Causes of death in liver cirrhosis patients seen on an outpatient basis]. AB - The immediate cause of death were studied in 122 patients with cirrhosis of liver, out of 236 patients with cirrhosis of liver under follow-up care observation in the course of 12 years. The average age of the deceased is 53,8 years, with a ratio males: females--2,3:1. The deceased were grouped according to the type of liver cirrhosis as follows: micronodular--63,1%, macronodular--15,6%, mixed--9,8%, primary biliary--6,6%, hemochromatosis--, 4,1% and the disease of Wilson--Konovalov--0,81%. Decompensated stage of cirrhosis was established in 77,9% from the deceased at the last examination and compensated--21,1%. Immediate cause for the death in the summed up group cirrhoses is: hepatic coma in 42,2%, acute hemorrhage with or without coma--32,3%, other causes--18,9%. Degeneration of liver cirrhosis into cancer was established in 9,01%. Cirrhosis degenerated more frequently in males. Hemochromatosis and micronodular cirrhosis are the ones that most frequently degenerated. PMID- 4024607 TI - [Serum immunoreactive trypsin in chronic pancreatitis patients]. AB - The serum immunoreactive trypsin (determined by RIA-gnost Trypsin of the firm Hochst) was studied in 30 patients with chronic pancreatitis: 16 patients in a stage of exacerbation and 14 patients with clinical remission. Via pancreozymin secretin test pancreatic exocrine insufficiency was established in all patients: 24 patients with moderate disorders and 6 patients with total secretory deficiency. The results were compared with a control group of 13 healthy subjects. In the mixed group of patients with chronic pancreatitis, serum immunoreactive trypsin did not differ from that of the control group (p greater than 0,05). The values of immunoreactive trypsin in serum, in the patients with chronic pancreatitis in a stage of exacerbation, are higher, with a statistical significance (p less than 0,001). In chronic pancreatitis, in a stage of remission, the level of serum immunoreactive trypsin is significantly lower as compared with the control group (p less than 0,01). The determination of serum immunoreactive trypsin could be used as a test in the diagnostics of recurrences of chronic pancreatitis but it is not a sure marker for the presence of pancreatic exocrine insufficiency. PMID- 4024608 TI - [Treatment of diffuse glomerulonephritis in systemic lupus erythematosus with a combination of anticoagulants, corticosteroids and immunosuppressors]. AB - The results from the combined treatment with anticoagulants (heparin and acenocoumarol), corticosteroids and immunosuppressors are reported in 27 patients with diffuse lupus glomerulonephritis. In 14 patients (51,9%) complete clinical laboratory remission was obtained, and in 9 patients (33,3%)--partial. Two patients (7,4%) deteriorated and one female of them--died. Two patients (7,4%) died from the complications in connection with the treatment. The following conditions are necessary for the attainment of favourable therapeutic effect: intravenous administration of 30 000 U heparin for at least 60 days; high initial dose of corticosteroids (60 mg prednisolone) in the course of 2-3 months or initiation with "pulse" methylprednisolone treatment (300 mg methylprednisolone intravenously for 3 to 5 days), when a shortening of the periods with the high initial doses to 1-2 months is possible; considerable duration of the treatment as a whole--at least I and 1/2 year; qualitative follow up care. With alternating intake of corticosteroids--the dose for two days, taken as a single dose every second day--reduces sharply the incidence and severity of the adverse effects, induced by them, but with no effect on therapeutic outcome. PMID- 4024609 TI - [Treatment of acute and chronic urological infections with azlocillin--clinical and microbiological research]. AB - The authors present their results from the treatment of urological infections with the new semisynthetic penicillin antibiotic azlocillin (acyl-ureide penicillin) in 86 patients with various, in kind and clinical manifestations, infections of the urinary system. The susceptibility was determined of the isolated bacterial causative agents of the urological infections to azlocillin and to the other antibacterial preparations available in our country. It was established that 52,7% of Gram-negative microorganisms were susceptible to the preparation, and over 80%--of the Gram-positive microorganisms. The highest number of susceptible strains were established in pseudomonas, coli, enterobacter, klebsiella and proteus. The results from the clinical study reveal that 51,2% of the patients were cured by the end of the therapeutic course and abatement or considerable improvement, was observed in all, of the clinical and paraclinical indices, suggesting urological infection. No allergic or toxic manifestations were observed. The absence of nephrotoxicity makes that new, for our practice, antibiotic extremely valuable for the patients with renal insufficiency. The most general conclusion from that study is that azlocillin, with its effectiveness, comes close to the most potent modern antibacterial preparations, with no toxicity characteristic for aminoglucoside antibiotics. PMID- 4024610 TI - [Scintigraphic study of the kidneys with a 99m Tc-ascorbic complex in chronic pyelonephritis patients]. AB - A scintigraphic study of the kidneys was carried out in 1780 patients with chronic pyelonephritis: 1308 with calculous and 472 with acalculous pyelonephritis. The scintigraphic finding was interpreted for each kidney separately. Diffuse damages of renal parenchyma was most often observed (47,6%), being, in the majority of the cases--bilateral. Disturbed drainage was established in 13,2%, dysfunction of one of the kidneys--in 18,8% and focal disturbed structure--in 5,4% of the kidneys studied. The results from the scintigraphic study were juxtaposed to the clinic of the disease and the data from laboratory and X-ray investigations. The scintigraphic study of the kidneys with 99m Tc-ascorbic complex is easy to perform, well tolerated by the patients, non-invasive method with no special risks, with minimal irradiation loading. Scintigraphy provides valuable information to the clinicians about the functional, structural and drainage disorders in the kidneys of patients with chronic pyelonephritis, allowing the control of the evolution of the disease and the effect of the treatment. PMID- 4024611 TI - [Mycoplasma as the causative agent of kidney infections]. AB - A total of 185 patients were investigated for M. hominis and mycoplasmal infection was established in 28 patients. In 2 of the patients mixed infection with E. coli was established and I with Staphylococcus aureus. Fifteen had pyelonephritis and 6--arterial hypertension, without positive data for pyelonephritis. The patients were treated with gentamycin and tetracycline according to the data of antibiograms of the isolated microorganisms. The criteria for admittance of the presence of mycoplasmal pyelonephritis are discussed. PMID- 4024612 TI - [Combined acute myocardial infarct and pulmonary thromboembolism with fatal outcome]. AB - A retrospective clinical and pathologicoanatomic analysis was made of 37 patients with the combination of acute myocardial infarction (AMI) and pulmonary thromboembolism (PTE), that had a lethal end. The following facts were established: The combination of AMI with PTE is established in 7.89% in AMI. All patients have several preconditioning factors for PTE, advanced age including. PTE advances usually in extensive anterior and anterior-posterior myocardial infarction, complicated with cardiac insufficiency. In rare cases, a reverse succession is likely--massive PTE with a following, most frequently posterior inferior AMI. The percentage of the undistinguished PTE in case of AMI is high- 46%. The diagnosis of PTE in AMI is made, with a high probability, in acutely advancing respiratory distress, tachycardia (tachyarrhythmia, pulmonary hypertension, loading of right ventricle, arterial hypotension, phlebothrombosis in the absence of data for extension of the myocardial infarction. ECG, roentgenography, laboratory investigations do not essentially improve the possibilities of making the diagnosis of PTE in AMI. PMID- 4024613 TI - [Symptoms of defects in the interrupted development of the bronchopulmonary system]. AB - On the base of the anamnestic clinical characteristic of 181 undergone operations with heart defects with stopped development of broncho-pulmonary system, its discussion is presented. The symptoms cough, expectoration, pain in the respective hemithorax, hemoptysis, etc. are discussed. Every patient with clinical diagnosis "chronic bronchitis" or "recurrent pneumonia" should be sent for thorough examination at qualified medical institution. PMID- 4024614 TI - [Changes in respiratory function, functional and true intrapulmonary shunts and acid-base state depending on the type of heart defect]. AB - The respiratory disorders in various kinds of heart defects were studied in 226 patients with acquired heart defects. The following indices were determined: external respiration, alveolar ventilation, alveolar-capillary diffusion, functional and real intrapulmonary shunts and acid-base state. The complex studies via numerous indices, juxtaposed in the separate defects, revealed various stages of manifestation of the respiratory disorders according to the kind of defect, at identical degree of cardiac insufficiency. The lightest proved to be the respiratory disorders in combined aortic defects and most manifested- in biaxial defects (mitral and aortic). In mitral defects with predominant stenosis, the respiratory disorders are better manifested as compared with those with predominant insufficiency, and for some of the indices--they are considerable. PMID- 4024615 TI - [Respiratory disorders in acquired heart valve defects with various degrees of heart failure]. AB - The respiratory disorders with various degrees of cardiac insufficiency were studied in 226 patients with acquired heart defects. The indices characterizing the external respiration, alveolar ventilation, alveolar-capillary diffusion, functional and real intrapulmonary shunts and acid-base state were followed up. The results from the numerous indices followed up significantly express the progressive intensification of respiratory disorders with the advancement of cardiac insufficiency. In stage I of cardiac insufficiency, prior to the manifestation of clinical signs of pulmonary stasis, distinct disturbances were established in DLCO, Qs/Qt, PaO2, which, to a great extent, characterize the early respiratory disorders and have a definite importance for the diagnostic and therapeutic behaviour. Most severe are the functional disorders in respiratory system in stage II B of cardiac insufficiency. PMID- 4024616 TI - [Our experience with the Impact 400 automatic analyzer in determining enzymes and substrates]. PMID- 4024617 TI - [2 cases of legionellosis in Greek citizens]. AB - Two cases of legionella pneumonia are reported in Greek citizens, treated at the Institute for Treatment of Foreigners--Medical Academy, Sofia. The patients mentioned are with grave basic diseases--pulmonary carcinoma. In one of them pneumonia was with a lethal end in spite of the adequate antibiotic therapy. PMID- 4024618 TI - [Small intestine perfusion. The authors' own method for the simultaneous performance of biopsy and perfusion of the human small intestine]. AB - The analysis of advantages and disadvantages of the technique and principles of the methods of small intestinal perfusion, used by various authors in the studies on resorption processes, provided grounds the authors to develop their own method. The system for infusion and aspiration by a combined probe is described. Details about the composition of perfusion solution, the technique of the study and calculation of resorption rate are reported. The advantages of the method are as follows: simultaneous performance of small intestinal glucose perfusion and biopsy of small intestine, good tolerance by the patients and availability of the elements needed for the construction of the probe and system for infusion and aspiration. The mean glucose resorption rate was 814,07 mumol/min/30 cm in 9 subjects with no small intestinal diseases and with normal histomorphological picture of small intestinal mucosa. PMID- 4024620 TI - [Microbial spectrum in chronic pyelonephritis and the drug sensitivity of the microorganisms]. AB - The authors studied the etiological spectrum of 226 patients with chronic pyelonephritis, with 926 microbic strains isolated from the urocultures. The most frequent microbic causative agents were E. coli (40,82%), Proteus (a total of 17,82%), Enterobacter (8,86%), Klebsiella (8,64%), Pseudomonas (6,16%), Enterococcus (5,94%). The drug susceptibility of the majority of the isolated gram-negative microorganisms versus ampicillin and chloramphenicol, widely used in out-patient department practice, is relatively low. An important condition for the effectiveness of the treatment is the consideration given to the susceptibility of the microbic strains, isolated from the uroculture. PMID- 4024619 TI - [Parallel morphological and functional research on chronic enterocolitis patients using the authors' own method for the simultaneous performance of perfusion and biopsy of the small intestine]. AB - Thirty two patients were studied with chronic enterocolitis and 9 patients without any small intestinal diseases, with normal histomorphological picture of small intestinal mucosa--control group. The method of simultaneous performance of perfusion and biopsy of small intestine was used. Glucose resorption rate in small intestine was studied and histomorphological, electron--microscopic and enzymologic (disaccharidases) studies were carried out on jejunal mucosa. Data about chronic enterocolitis without atrophy were established in 17 patients, in 10--initial partial atrophy, in 5--advanced partial and subtotal atrophy of jejunal mucosa. Reduced glucose resorption rate was established in small intestine in the patients with chronic enterocolitis as compared with that of the control group. Glucose resorption rate correlates with the severity of the histomorphological changes in small intestinal mucosa. Disturbed resorption rate was established via jejuno--perfusion in patients with clinically not manifested syndrome of malresorption and absence of histomorphological changes in small intestinal mucosa, but with established ultrastructural changes in enterocytes. PMID- 4024621 TI - [Causative agents of urologic infections and their sensitivity to the most frequently used antibiotics and chemotherapeutic agents (data from the Clinic for the Therapy of Internal Diseases and Clinical Pharmacology for 1984)]. AB - The causative agents of uroinfections were studied among the patients at the Clinic of therapy of internal diseases and clinical pharmacology during 1984. Significant bacteriuria was established in 279 out of 485 patients, with 1475 urine inoculations performed, 14 with mixed flora. The highest is the share of E. coli--50,5 per cent, followed by Proteus--25,7 per cent. No essential change was established in the microbiological spectrum of the causative agents of uroinfections as compared with that from 1961-1970. Good susceptibility was established to ampicillin but only of Enterococcus, to chloramphenicol of E. coli, Klebsiella, Enterobacter. The susceptibility of all microorganisms to gentamycin and nalidixic acid was very good. The susceptibility to doxycycline was poor. The treatment is recommended only after precise microbiological study. PMID- 4024622 TI - [Epidemiology of myocardial infarct in the region of Polyclinic XXIII]. PMID- 4024623 TI - [Outpatient polyclinic rehabilitation of patients who have had a myocardial infarct]. AB - Rehabilitation of patients after myocardial infarction has been organized at polyclinical conditions. Forty four patients, aged from 30 to 56, with a duration of the infarction--3-4 months, in a good somatic state and no complications at present, were rehabilitated. The rehabilitation programme was conducted daily for one month with respective tests of loading. As a result, 52,3 per cent of the total number of patients, have completely restored their capacity for work and- back to their previous labour activity, 34.I per cent were transferred to facilitated labour conditions and only 13,6 per cent were permanently disabled. The last are with rhythm disorders and residual angina pectosis. The rehabilitation period lasted from 6 to 12 months since the onset of infarction. Our data confirm the adequacy and necessity of proper rehabilitation measures under polyclinical conditions. PMID- 4024624 TI - [Clinical and echocardiographic symptoms of mitral valve rupture]. AB - The diagnostic sensitivity, specificity and predicting accuracy of the various alterations, established by one-dimensional echocardiography (M-EchoC) were determined in 23 patients with rupture of mitral chordae. The diagnosis of mitral insufficiency, resulting from chordal rupture was confirmed at operation, with angiocardiography and/or bi-dimensional echocardiography. Almost all MEchoC alterations were with a relatively low sensitivity (10-50%), high specificity (60 100%) and moderately high predicting accuracy (50-80%). Of more essential diagnostic significance--moderate sensitivity and high specificity with high predictive accuracy, are the following alterations: systolic fibrillation of mitral valve, diastolic fibrillation of mitral valvular cusps, paradoxical (chaotic) movement of posterior mitral cusp during diastole. Very little sensitivity (10%) but with high specificity (100%) was established in pathological systolic echoes in the cavity of left auricle. In the majority of the cases, the rupture of mitral chordae induced grave mitral regurgitation, conditioning the various stages of cardiac insufficiency. Relatively rare is the light to moderately grave mitral regurgitation with stable hemodynamics and preserved functional capacity. PMID- 4024625 TI - [Treatment of essential hypertension (hypertensive disease) with verapamil and hydrochlorothiazide]. AB - Thirty two patients with essential hypertension, stage I and II according to WHO classification, were treated according to the following schedule: period A--3 X 1 dragee placebo--3 weeks; period B--3 X 1 dragee placebo + 25 mg hydrochlorothiazide in the morning--6 weeks; period C--3 X 1 dragee isoptin 80 mg + 25 mg hydrochlorothiazide in the morning--6 weeks; period D--3 X 1 dragee placebo--2 weeks. Significant decrease of systolic and diastolic arterial pressure was established during period B as compared with period. A. The addition of isoptin to the treatment during period C led to additional reduction of arterial pressure, with no manifestations of severe adverse effects, as observed in 15,6 per cent of the treated patients. The treatment of essential hypertension with isoptin and esidrex is effective and well tolerated with no reciprocal potentiation of the adverse effects of the two preparations, broadening the possibility of successful treatment of essential hypertension. PMID- 4024626 TI - [Deformations in the shape of the P wave--the frequency of the double-peak P wave in healthy persons and patients with atrial loading (studied with ECG and orthogonal ECG systems)]. PMID- 4024627 TI - [Clinical laboratory characteristics of croupous pneumonia in recent years (based on data from the N. I. Pirogov Institute (RNPISMP) for 1980-1984)]. AB - The results from retrospective clinical-laboratory study of 110 patients are reported, discharged with the final clinical diagnosis--croupous pneumonia, from the clinics of internal secretion of the institute for the period 1980 to 1984 including. It was established that the disease has become, in the last several years, more frequent, affecting younger subjects, with a predomination of males; the cases with sudden onset, occurring in younger people, have been reduced. In 1/4 of the cases bilateral involvement of the lungs by the disease was observed but at the same time, only several segments were very often involved and not the whole lobe; in about 1/3 of the cases, pleura was also involved. No cases with leukopenia were reported and leukocytosis was established in about 2/3 of the patients; shifting to the left is a more frequent sign of the disease as compared with leukocytosis. PMID- 4024628 TI - [Immunoglobulins and diabetic microangiopathy]. AB - Blood level of immunoglobulins A, M and G were studied in 166 diabetics with present or absent microangiopathy. Regardless of the significant elevation of IgA and IgG, for the whole group, reduction of IgM respectively, no significant difference was established in their level among the subgroup with present or absent retino- and nephropathy as well as among those with proliferative and non proliferative retinopathy. PMID- 4024629 TI - International nonproprietary names for pharmaceutical substances. PMID- 4024630 TI - Proceedings of the Commonwealth Caribbean Medical Research Council, 30th scientific meeting. Kingstown, St. Vincent and the Grenadines, April 24-27, 1985. PMID- 4024631 TI - American visceral leishmaniasis (kala-azar). AB - Visceral leishmaniasis (kala-azar) is an important cause of morbidity and mortality in widely scattered areas of the world. To better characterize the South American form of the disease, the clinical and laboratory manifestations of 29 patients admitted to hospital (18 male and 11 female patients, mean age 4.9 years), were assessed in an endemic area in northeastern Brazil. Fever, weight loss, pronounced splenomegaly, hepatomegaly, anemia, thrombocytopenia, relative neutropenia, hypoalbuminemia and hypergammaglobulinemia were found in the majority of patients. Symptoms were often present for two or more months before diagnosis. Secondary infections complicated many cases; there were ten cases of pneumonia and half of the patients had one or more intestinal parasites. The average length of hospital stay was 27 days; all patients were treated with meglumine antimoniate (Glucantime). The mortality rate was 3%. American visceral leishmaniasis remains an important disease among children living in endemic areas. PMID- 4024632 TI - Computed tomography in cases of coccidioidal meningitis, with clinical correlation. AB - Cranial computed tomographic (CT) scans of 22 patients with coccidioidal meningitis were reviewed and their clinical course was analyzed. Abnormalities of the ventricular system or the basilar cisterns or both were present in 16 instances. Although it is not a definitive diagnostic tool, the CT scan is helpful in suggesting a diagnosis of coccidioidal meningitis and in predicting the prognosis of patients affected by the disease. PMID- 4024634 TI - Stress and medical training. PMID- 4024633 TI - Managing patients who have myasthenia gravis. PMID- 4024635 TI - Neurological paraneoplastic syndromes. PMID- 4024636 TI - Multifocal eosinophilic granuloma with a pituitary stalk lesion. PMID- 4024637 TI - Kaposi's sarcoma presenting as homogeneous pulmonary infiltrates in a patient with acquired immunodeficiency syndrome. PMID- 4024638 TI - Management of stroke. PMID- 4024639 TI - Type II diabetes mellitus. PMID- 4024640 TI - Cinnamon oil burn. PMID- 4024641 TI - Protective helmets for infants and children on bicycles. PMID- 4024642 TI - 'Baby Doe'--a medical ethical issue. PMID- 4024643 TI - Outpatient treatment of chronic obstructive pulmonary disease--a practitioner's guide. PMID- 4024644 TI - [Letters of discharge from a University Department of Medicine. Attempt at an analysis of their contents]. AB - 498 discharge letters, written by physicians at the Second Department of Medicine, University of Vienna were subjected to the following content analysis: procedures employed to reach a diagnostic result, length and preferred content of letters, delay between discharge of patient and posting of letter and relationship between pragmatic versus knowledge-oriented concepts. Routine hospital diagnostic procedures achieved a marked increase in accuracy in terms of medical diagnosis over initial admittance diagnosis. Enlarged diagnostic evaluation mostly occurred due to the assistance of X-rays. Letters addressed to general practitioners were longer and contained more assessment of the patient's condition than letters to specialists. Letters on average left the hospital 30 days after the patient's discharge. PMID- 4024645 TI - [DSM III personality diagnosis in a group of chronic offenders]. AB - A group of chronic offenders (n = 44) was investigated and their personality disorders coded according to two different methods, namely the ICD 9 (International Classification of Diseases 9) and the American DSM III (Diagnostic and Statistical Manual III). The total number of personality disorders diagnosed by DSM III was less than by ICD 9. This cannot be attributed only to the fact that according to DSM III cyclothymic disorders do not have a direct correlate in axis II-personality disorders, but are, instead, assigned to the group of affective disorders. The majority of persons in whom the diagnosis of cyclothymic personality disorders was made on ICD 9 were rated as having one of the "extroverted personality disorders" in DSM III. If the personality disorders are combined to form three groups - (a) eccentric (close to psychoses), (b) extroverted and (c) introverted - then the overall correlation between ICD 9 and DSM III is considerable. The DSM III system promises a higher reliability due to the existence of criteria for inclusion and exclusion. The diagnosis "borderline personality disorder" was compared with the DIB Gunderson interview (kappa 0.89). In the international classification DSM III borderline personality disorder was equivalent to a diagnosis of cyclothymic, irritable, hysteric or sociopathic personality disorder. PMID- 4024646 TI - [Our experiences with percutaneous litholapaxy]. AB - Percutaneous litholapaxy is a non-invasive method in the surgery of kidney stones. We prefer the one-step-proceeding--the punction, the dilatation and the intrarenal instrumentation in one session. With this method in 24 cases we have dislocated 9 pelvic-stones, 13 calix-stones and 3 upper ureteral stones which could not remove themselves. Postoperative 4 patients had small residual-stones, 2 of them removed spontaneously without colics still in time of the hospitalization. Thinking of the minimal morbidity and invasiveness we mean, we can recommend the percutaneous stone-removing to our patients with nephrolithiasis after an exact exploration in the future, too. PMID- 4024647 TI - [Ventriculo-cardiac shunt in an adult with a fatal complication: diagnostic and therapeutic aspects. Case report]. AB - A 29-year-old patient with a Pudenz-Heyer-shunt was assigned to examination because of exercise-induced dyspnea after 10 years of uncomplicated follow-up. Echocardiography established the diagnosis of advanced cor pulmonale, the cause being multiple pulmonary embolism produced by thrombotic layers on the shunt tube. During anticoagulant therapy right heart decompensation with fatal outcome occurred. PMID- 4024648 TI - [Neurogenic bladder emptying disorder. History and clinical studies]. AB - History and clinical examination in patients with neurogenic bladders reveal a lot of facts which postpone misinterpretation of urodynamic results and save time in diagnosing neurogenic disorders. They are under-stood as signs on the way to a clear and exact diagnosis. PMID- 4024649 TI - [Organic psychosyndrome with and without lithium therapy]. AB - After two years of treatment with Lithium-salts we did not find organic brain syndrome. Lithium treated patients have improved in thinking, concentration, the short-time memory, attention and conception. Control group did not have this improvement. Lithium-treated patients seemed to have more self-confidence, more flexibility and are able to master problems in a better way. Control group patients were more dependent on their moods and therefore did not improve in efficiency. PMID- 4024650 TI - Health needs of women as they age. PMID- 4024651 TI - Psychological aspects of aging in women. AB - Older women are forced to cope with many societal myths and negative stereotypes. This paper reviews the influence of these stereotypes as well as some of the other psychological concerns of women who are aging. Losses such as widowhood and divorce as well as the problem of loneliness are discussed. PMID- 4024652 TI - Alzheimer's disease: a practical, psychological approach. AB - Alzheimer's Disease affects approximately two million people. It is a crippling, organic brain disorder that causes loss of recent memory, intellectual deterioration, unpredictable behavioral changes, and personality deterioration. The fourth leading cause of death among the elderly, it also affects younger people. The disease has two victims, the Alzheimer patient and the caregiver. Caregivers often experience shame, embarrassment, denial, frustration, anger, depression, and guilt as they care for an Alzheimer patient. This paper provides information about the disease and it's manifestations, along with practical suggestions to help both the Alzheimer patient and the caregiver. PMID- 4024653 TI - Hypertension in women: progress and unsolved problems. AB - Hypertension is the most common cause of increased risk for heart and vascular disease in the adult population. Both men and women are at risk for hypertension and both benefit from anti-hypertensive therapy. However, hypertension tends to be less prevalent in women and is better tolerated; hypertensive women have fewer strokes and heart attacks than do hypertensive men. Women may develop reversible hypertension due to use of birth control pills. Another form of curable secondary hypertension, renal artery stenosis caused by fibromuscular dysplasia, is much more frequent in young women than men. Antihypertensive drug treatment for severe hypertension benefits both sexes, although clinical trials establishing this have been conducted only in men. There is no proof that white women with mild hypertension benefit from antihypertensive drug therapy. Non-drug approaches including weight reduction, change in diet, and exercise may be equally beneficial. PMID- 4024654 TI - Blue book 1985. PMID- 4024655 TI - Fluoride and bone: an unusual hypothesis. AB - Given the total body weight, the weight of the skeleton and the proportion of minerals in the skeleton, a simple formula can be used to estimate the accumulation of fluoride in the skeleton over periods of years. It would appear that daily intakes of fluoride considered beneficial to developing teeth may, if ingested throughout adult life, lead to skeletal fluorosis of varying degrees in a significant proportion of the population. To date, the accumulation of fluoride in the skeleton seems to have been ignored as a possible aetiological factor in certain metabolic bone disorders now common in the middle-aged and elderly. The unusual hypothesis put forward in this paper suggests that a daily intake of fluoride derived from a multiplicity of sources, and which is now generally considered as 'safe', may in fact be potentially harmful over long periods of time. PMID- 4024656 TI - Distribution of cysteine conjugate beta-lyase in gastrointestinal bacteria and in the environment. AB - A cysteine conjugate beta-lyase was detected in 24 of 43 gastrointestinal bacteria tested, and from mixed populations of bacteria obtained from lake, river and soil samples. These bacterial cysteine conjugate beta-lyases catalyse the cleavage of the thioether linkage of both an S-alkyl- and an S-aryl-linked cysteine conjugate (2-S-cysteinyl-N-isopropylacetanilide (cysteine conjugate of propachlor) and S-(2-benzothiazolylcysteine), respectively). A cysteine conjugate beta-lyase was isolated from Eubacterium limosum at levels at least 16-fold greater than those from any other gastrointestinal bacterial tested. This enzymic activity was present from the late lag phase through the stationary phase of growth of the bacteria. Maximum activity occurred in the mid log phase. A cysteine conjugate beta-lyase isolated from animal and plant tissues cleaved only the S-aryl-linked cysteine conjugate (S-(2-benzothiazolyl)cysteine) and generally had less enzymic activity than enzymes isolated from the bacteria. Glutathione-S transferase activity was not detected in the 43 gastrointestinal bacteria tested, except for a low level (0.6 nmol/min per mg) of activity in Escherichia coli. No S-methyl transferase activity was detected in the gastrointestinal bacteria or mixed populations of bacteria tested. PMID- 4024657 TI - trans,trans-Muconic acid, an open-chain urinary metabolite of benzene in mice. Quantification by high-pressure liquid chromatography. AB - A sensitive h.p.l.c. method is described which separated urinary metabolites from benzene-treated male CD-1 mice. Phenol, trans,trans-muconic acid and quinol in the 48 h urine accounted, respectively, for 12.8-22.8, 1.8-4.7 and 1.5-3.7% of the orally administered single dose of benzene (880, 440 and 220 mg/kg body wt.). Catechol occurred in trace amounts. Ascorbic acid was used to adjust urine pH and increase the extraction efficiency of metabolites, especially muconic acid. It allowed an accurate estimation of quinol by preventing its auto-oxidation. trans,trans-Muconic acid was identified and was unique to benzene as none was detected in urine of mice dosed orally with phenol, catechol or quinol (250, 150 and 200 mg/kg, respectively). The potential existence of a toxic benzene metabolite in the form of an aldehyde precursor of muconic acid in vivo is discussed. PMID- 4024658 TI - Oxidative metabolism of carbazeran in vitro by liver cytosol of baboon and man. AB - The metabolism of carbazeran has been investigated in vitro using liver cytosol from dog, baboon and man. Carbazeran was not metabolized in cytosol prepared from dog liver but was rapidly metabolized to a single product in baboon- and human liver cytosol. The product was identified as 4-hydroxy carbazeran. The enzyme responsible for the 4-hydroxylation of carbazeran in vitro was shown by the use of inhibitors to be liver aldehyde oxidase. Species differences in the metabolism of carbazeran in vitro correlate well with studies in vivo; these showed that following an oral dose to man and baboon, the compound was almost completely cleared via pre-systemic 4-hydroxylation, whereas in the dog, this metabolic route appeared unimportant. PMID- 4024659 TI - Effect of promethazine and isosafrole on rat-hepatic microsomal mono-oxygenase activity: comparison with classic inducers phenobarbitone and beta naphthoflavone. AB - The characteristics of induction of rat-hepatic microsomal mono-oxygenase activity by promethazine and isosafrole have been investigated and compared with the classic inducers phenobarbitone and beta-naphthoflavone. Both promethazine and isosafrole pretreatments result in increased cytochromes P-450, and enhanced NADPH-cytochrome c reductase, aminopyrine N-demethylase, dichloronitroanisole O demethylase, ethoxycoumarin O-deethylase and ethoxyresorufin O-deethylase activity. Isosafrole but not promethazine increased the liver to body weight ratio. It is concluded that promethazine and isosafrole pretreatment produces an induction of the rat-hepatic microsomal mono-oxygenase system which shows both phenobarbitone- and polycyclic aromatic hydrocarbon-type characteristics. PMID- 4024660 TI - Excretion and metabolism of di(2-ethylhexyl)phthalate in man. AB - Di-(2-ethylhexyl)phthalate (DEHP) taken orally by two volunteers (30 mg each) was excreted in the urine to the extent of 11 and 15% of dose. After enzymic hydrolysis the urinary metabolites (derivatives of mono (2-ethylhexyl)phthalate) were methylated and identified by g.l.c.-mass spectrometry (C.I.), and the quantitative distribution of conjugated and free metabolites determined. DEHP taken by the same volunteers over a period of four days at doses of 10 mg daily gave no evidence of accumulation; 15 and 25% of the total dose was recovered in the urine. PMID- 4024661 TI - The inhibition of bacterial bioluminescence by xenobiotics. AB - The effect of various xenobiotic substrates of microsomal cytochrome P-450, including dimethylaniline, ethylmorphine, hexabarbital and aminopyrine, on the bioluminescence of the bacteria Vibrio fischeri and the bacterial luciferase mixed-function oxidase system is described. These compounds are effective inhibitors of the luminescence reaction. The inhibition provided evidence for the competitive nature of the interactions between xenobiotics and an aliphatic aldehyde, which is a substrate of bacterial luciferase, at the binding site for cytochrome P-450. The bioluminescence method is suitable for the analysis of metabolism and detoxication of various xenobiotics. PMID- 4024662 TI - Metabolism of ethylbenzene in the rat during long-term intermittent inhalation exposure. AB - After exposure of rats to atmospheres of 50, 300 or 600 p.p.m. ethylbenzene six hours/day, five days/week, for a max. of 16 weeks, the concn. of ethylbenzene in perirenal fat and the urinary excretion of 1-phenylethanol, omega hydroxyacetophenone, mandelic, phenylglyoxylic, hippuric and phenaceturic acids were measured at the second, fifth and ninth weeks. Excretion of metabolites into urine increased in a dose-related manner, but less than linearly. The level of exposure, but not the duration of exposure, markedly affected the pattern of the metabolites in the urine. The concn. of ethylbenzene in perirenal fat was low at 50 p.p.m., high at 300 p.p.m. and higher still at 600 p.p.m., but not in proportion to the increased dose. PMID- 4024663 TI - Disposition in the rat of buprenorphine administered parenterally and as a subcutaneous implant. AB - Disposition of [15, 16(n)-3H]buprenorphine in the rat has been investigated after a single 0.2 mg/kg i.v. bolus dose and continuous administration via a s.c. implantable long-acting delivery system. After the i.v. injection, the tri exponential decay of drug from brain occurred with t1/2 values of 0.6, 2.3 and 7.2 h, respectively (plasma t1/2 0.5, 1.4 h, third phase not estimated due to sustained concn.) Decay of drug from another high-affinity binding site in brain occurred with t1/2 values of 1.1 and 68.7 h, respectively. Fat and lung had higher concn. than other tissues and plasma. No metabolites of drug were detected in brain. Unmetabolized drug excreted in urine and faeces one week after i.v. injection were 1.9 and 22.4% of dose, respectively, and 92% of the dose was accounted for in one week. Urinary metabolites (%) were: conjugated buprenorphine 0.9; norbuprenorphine (free 9.4, conjugated 5.2); tentative 6-O desmethylnorbuprenorphine (free 5.4, conjugated 15.9). Peak plasma concn. of buprenorphine occurred four weeks after s.c. implantation of a long-acting 10 mg 3H-buprenorphine pellet, and apparent dissociation half-lives of drug from low- and high-affinity binding sites in brain were 4.6 and 6.8 weeks, respectively. Fat, spleen and skeletal muscle had higher concn. than other tissues and plasma. No significant difference in brain morphine concn. was observed in placebo and nonlabelled buprenorphine-pelleted animals after a 2 mg/kg i.v. challenge dose of 3H-morphine. This study emphasizes the importance of high-affinity binding of buprenorphine in brain and subsequent slow dissociation as a prime factor in its prolonged agonist/antagonist effects and higher potency than other narcotic agonists. PMID- 4024664 TI - Biochemical and morphological effects of long-term inhalation exposure of rats to ethylbenzene. AB - Male Wistar rats were exposed (six hours/day, five days/week) to 0, 50, 300 or 600 p.p.m. of ethylbenzene vapour in the air, and killed after 2, 5, 9 or 16 weeks of exposure. After 600 p.p.m., liver-microsomal protein but not cytochrome P-450 concn. was slightly increased; NADPH-cytochrome c reductase was increased maximally by 30% (1.3-fold), 7-ethoxycoumarin O-deethylase (1.8-fold) and UDPG transferase (2.3-fold). The increase in liver-cytosolic D-glucuronolactone dehydrogenase paralleled the glucuronidation activity (less than or equal to 2 fold). In the kidneys, only 7-ethoxycoumarin O-deethylase (less than or equal to 3.5-fold) and UDPG-transferase (less than or equal to 1.8-fold) showed dose related increases. Ethylbenzene exposure did not deplete hepatic glutathione (GSH); kidney GSH was slightly increased (less than or equal to 1.3-fold) according to dose. Urine excretion of thioethers was increased with dose, and at 600 p.p.m. was eight times control levels. At 600 p.p.m. there was no increase in serum alanine aminotransferase activity, and liver cells showed slight proliferation of smooth endoplasmic reticulum, slight degranulation and splitting of rough endoplasmic reticulum and enlarged mitochondria, but no necrosis. PMID- 4024665 TI - Phenolic metabolites of thioridazine in man. AB - After oral administration of thioridazine or mesoridazine to man, faecal extracts contained mainly unconjugated 7-hydroxy-thioridazine and its demethylated analogue, together with some 3-hydroxy-thioridazine, and 7-hydroxy derivatives of sulphoridazine and desmethyl sulphoridazine. In contrast, urine contained free 7 hydroxy-mesoridazine, and no free 7-hydroxy-thioridazine was detectable. Conjugates of all these phenols were also found. After oral sulphoridazine administration (thioridazine side-chain sulphone), urine contained mainly 7 hydroxy-sulphoridazine and faeces both 7-hydroxy-sulphoridazine and its desmethyl analogue. Sulphoridazine metabolism is therefore much simpler than that of thioridazine. This different elimination pattern in faeces and urine may be due to reduction of sulphoxides but not sulphones by intestinal bacteria. PMID- 4024666 TI - Further studies of trans-sobrerol metabolism: rat, dog and human urine. AB - The urinary metabolites of d, l-trans-sobrerol were investigated after oral administration to rats, dogs and humans. Structural analysis of the urinary metabolites indicates that allylic hydroxylation, oxidation and glucuronylation are the common interspecies modes of trans-sobrerol biotransformation. Comparison of the findings of trans-sobrerol with previous investigations of cyclic monoterpenes shows similarities in their metabolism in vivo, including the resistance to oxidation of the cyclic trisubstituted double bond. PMID- 4024667 TI - Fast-atom bombardment and electron-impact mass spectrometry of N hydroxyarylamines, active intermediates of mutagenic aromatic amines. AB - Thermally labile N-hydroxyarylamines, which are the active metabolites of carcinogenic/mutagenic aromatic amines and show potent direct mutagenicity, were studied by fast-atom bombardment (F.A.B.) mass spectrometry and electron-impact (E.I.) mass spectrometry. The protonated molecular ion [M + H]+ and the molecular ion [M]+ were observed at high intensity in the F.A.B. mode. The fragment ions corresponding to [M + H-16]+, [M + H-17]+ and [M-16]+, [M-17]+, [M + H-32]+ and [M-32]+ were also observed characteristically. The quasimolecular ion peaks were shifted up by the numbers of active hydrogens in molecules after the hydrogen deuterium exchange with [hydroxy--2H3]glycerol and 2H2O. The formation of the ions continued stably throughout the period of measurement, and the decomposition of the samples did not occur in the F.A.B. ion source, compared with the E.I. mode. Hence, it is suggested that the F.A.B. technique is useful for the analysis of the heat-labile toxicologically important N-hydroxyarylamines. PMID- 4024668 TI - Ligand-complex formation between cytochromes P-450 and P-448 and methylenedioxyphenyl compounds. AB - The formation of ligand complexes between hepatic microsomal cytochrome P-450 and safrole, isosafrole and other methylenedioxyphenyl compounds was studied in vivo and in vitro in rats pretreated with either phenobarbital or 3 methylcholanthrene. Both the phenobarbital-induced cytochrome P-450 and the 3 methylcholanthrene-induced cytochrome P-448 metabolically convert safrole, isosafrole, and those metabolites possessing an intact methylenedioxy group, to reactive metabolites which then interact with the cytochromes to form ligand complexes. Formation of these ligand complexes was accompanied by loss of mixed function oxidase activities, and dissociation of the complexes with the type I substrate biphenyl restored activities. Safrole and, to a lesser extent, 1' hydroxysafrole formed complexes in vivo when administered to phenobarbital pretreated rats; none was obtained with epoxysafrole. However, when administered to 3-methylcholanthrene-pretreated animals all three compounds formed complexes, safrole being the least effective. Epoxysafrole and 1'-hydroxysafrole administered to phenobarbital-pretreated rats resulted in slight inhibition of the type I binding of safrole to liver microsomal P-450 in vitro; in contrast, with 3-methylcholanthrene-pretreated animals marked competitive inhibition was observed. This study shows that oxidation of the allyl chain of safrole analogues enhances their affinity for cytochrome P-448, but not for cytochrome P-450, and further demonstrates that these cytochromes possess distinctly different binding sites. PMID- 4024669 TI - Metabolic studies of a podophyllotoxin derivative (VP16) in the isolated perfused liver. AB - The metabolism of VP16 was studied in isolated perfused rat liver. The rate of elimination into the medium and excretion in bile were determined by h.p.l.c. with u.v. detection. With high VP16 concentrations (180 micrograms/ml medium), the elimination half-life of the compound was prolonged markedly (156 v. 45 min for lower doses), the percentage recovered in bile was more than halved and drug accumulation in the hepatic tissue was three times greater. These findings indicate saturation of metabolism and of biliary elimination during high-dose treatment. The presence of glucuronides in the bile of VP16 perfused livers indicates that VP16 undergoes conjugation with glucuronic acid. Formation of picro isomer of VP16 in the liver also occurs. PMID- 4024670 TI - Spectral and inhibitory interactions of methylenedioxyphenyl and related compounds with purified isozymes of cytochrome P-450. AB - Spectral and inhibitory interactions of two methylenedioxyphenyl (MDP) compounds (dihydrosafrole (DHS) and 4,5-dichloro-1,2-methylenedioxybenzene (DCMB] and 4-n butyl dioxolane (BD) were studied in vitro in reconstituted systems incorporating cytochromes P-450b and P-450c, purified respectively from hepatic microsomes of phenobarbital (PB)- and beta-naphthoflavone (beta NF)-treated rats. In NADPH fortified reconstituted systems containing P-450b, DHS yielded a stable type III spectral complex with peaks at 428 and 458 nm; a complex with a single 456 nm peak was formed in systems containing cytochrome P-450c. DCMB formed unstable 456 458 nm spectral complexes with both isozymes, and BD generated an unstable complex with a single Soret peak near 428 nm with cytochrome P-450b; no spectral interaction occurred between BD and cytochrome P-450c. Carbon monoxide was formed in incubations of DCMB with both isozymes but was not observed with either DHS or BD. Marked selectivity was observed in the ability of the test compounds to inhibit selected mono-oxygenase reactions in the reconstituted systems. Thus, while DHS was an effective inhibitor of cytochrome P-450b-mediated ethoxycoumarin O-deethylase (ECD), it failed to inhibit aldrin epoxidase (AE) in the same system; DCMB and BD inhibited both of these reactions. In reconstituted systems incorporating cytochrome P-450c, DHS and DCMB, but not BD, were effective inhibitors of ethoxyresorufin O-deethylase (ERD) activity but none of the compounds showed any inhibitory activity towards aryl hydrocarbon (benzo[alpha]pyrene)hydrolase (AHH) activity. The results indicate that metabolite complex formation with cytochrome P-450 is not the sole criterion for inhibition of mono-oxygenase activity by MDP and related compounds, and that in some cases type I competitive interactions at the substrate binding sites may be the primary contributing factor. PMID- 4024671 TI - [Hormonal contraception and cancer risk]. PMID- 4024672 TI - [Therapy of epicondylitis humeri]. PMID- 4024673 TI - [Surgical and technical prerequisites for the rehabilitation of enterostoma wearers]. PMID- 4024674 TI - [Recommendations for the evaluation and assessment of electrocardiograms of adolescents and adults. Short programmed course. 16. Partial program V: Interpretation, correlation and documentation]. PMID- 4024675 TI - [Truth is all]. PMID- 4024676 TI - [Infrared erythema]. AB - This article deals with the immediate effect of infra-red (IR) irradiation on human skin. The cutaneous response to IR significantly differed from that to polychromatic UV rays. The IR erythema showed a reticular pattern and was monophasic. Minimal erythema (ME) appeared without latency and faded a few minutes later. Induction of IR-ME required a radiation doses about 15,000 times higher (187-295 J/m2) than was needed for UVB erythema. The maximum erythema also occurred immediately after exposure to IR and faded away within one to four hours. The response was biphasic in only one of 28 test persons. Histological studies revealed dilated vessels and perivascular accumulation of degranulated mast cells. PMID- 4024677 TI - [Effect of infrared radiation on the kinetics of the guinea pig's epidermis cells. Comparison with UV radiation effect]. AB - In vivo exposition of guinea pig epidermal cells to infra-red irradiation (IR) led to significant, biphasic reduction of the proliferating activity after 6 h and 72 h. Not before 168 h after exposure, the proliferating activity rose above the normal rate. The quantitative alterations of DNA-proliferating cells went along with prolongation of the S-phase and the cell cycle. UV-irradiated cells react earlier by reduction of the DNA-proliferating activity directly followed by stages of hyperproliferation. PMID- 4024678 TI - [Budd-Chiari syndrome following dacarbazine therapy of malignant melanoma--an avoidable complication?]. AB - A 51-year-old female patient died of Budd-Chiari syndrome during treatment with adjuvant DTIC mono-chemotherapy for malignant melanoma. We report on clinical course and laboratory findings in detail. Differentiating BCS from VOD, we describe the liver damages referring to the latest findings about the effect of DTIC in fibrinolysis. In order to prevent further lethal complications, we suggest to regard pre-existing liver damage as a contra-indication for DTIC therapy; to prefer intraspinal anesthesia for malignant melanoma of the lower extremities; to avoid hepatotoxic drugs and alcohol during chemotherapy; to protect DTIC from light; to extend the interval between first and second cycle. Laboratory data, the "finger-prints" of DTIC, are unreliable. Great attention should be paid to clinical findings which may justify immediate and high dose corticosteroid therapy as well as intensive care monitoring. PMID- 4024679 TI - [Simultaneous occurrence of metageria and Gottron's acrogeria in one family]. AB - We report on a 17-year-old patient suffering from generalized mottled hyperpigmentation and multiple telangiectatic lesions of the skin. The subcutaneous fatty tissue was lacking or deficient. The patient showed a bird like face. The cutaneous changes had been present since birth. X-ray studies revealed acro-osteolysis of the hands and feet. The metabolic and endocrine data were within normal ranges except of latent hypothyroidism. The clinical picture presented all criteria of metageria. The patient's mother and sister showed similar cutaneous changes, however, restricted to the distal parts of the extremities. We diagnosed acrogeria Gottron. The incidence of both metageria and acrogeria in one family makes metageria as an independent entity doubtful. PMID- 4024680 TI - [Alcohol and fertility--from the andrological point of view]. AB - We report on the present views on disturbances regarding spermatogenesis caused by chronic abuse of alcohol which still are partly based on findings from the year 1910. We are also presenting results of semen analysis in alcoholics. There is some evidence that alcohol-toxic damage of the testes may occur immediately. Regarding alcohol-toxic effects, we discuss some biochemical conceptions as there are the metabolism of Vitamin A and possible effects on the steroid reductases in particular. Our own studies have revealed some disturbances with regard to the gestagen metabolism of chronic alcoholics. PMID- 4024681 TI - [Physical principles of the Doppler echocardiography determination of heart minute volume]. AB - By means of Doppler echocardiography to measure blood flow velocity in the aorta and echocardiographic imaging to measure vessel diameter cardiac output can be assessed noninvasively in selected patients. This paper presents the underlying physical principles and discusses resulting aspects of measurement and limitations of the technique. PMID- 4024682 TI - [Noninvasive determination of stroke volume with spectral Doppler echocardiography]. AB - To assess the determination of volume flow by Doppler echokardiography 15 patients were studied twice in intervals of 2 to 6 hours. Cardiac output was determined simultaneously by thermodilution and by Doppler echocardiography. In three patients (20%) no Doppler signal could be recorded. In the 24 successful determinations a correlation of r = 0.93 was found between the two techniques. Mean deviation was 0.57 l/min (0.15-1.16), 9% (1-20%) respectively. With serial measurements the correlation for changes in cardiac output was 0.94. Mean deviation was found to be 0.47 l/min (0.12-1.16), or 75% (9-395%). Thus, gross estimation of cardiac output by Doppler echocardiography seems possible. However, it cannot be judged as of yet whether a more than semiquantitative estimation of individual cardiac output changes is possible nor whether further information can be obtained besides that which is clinically available. PMID- 4024683 TI - [Frequency, localization and extent of local wall function disorders of the left ventricle in patients with rheumatic mitral valve diseases]. AB - In 59 patients with rheumatic mitral valve disease, local wall motion was assessed by analysing the diastolic and systolic left ventricular silhouette from biplane angiograms with a quantitative radial axes model using 90 radii in each projection. The left ventricle was dissected into 4 segments in the RAO and 2 segments in the LAO projection and a mean radii shortening for each segment was calculated. 27 patients had pure severe mitral stenosis (MS), 10 patients mitral insufficiency (MI) and 22 patients combined mitral valve disease (MSMI). A mean radii shortening less than 25% was diagnosed as wall motion abnormality. In 78% of all patients wall motion abnormalities could be detected in at least one segment. 32% of patients with MS, 27% of patients with MI and 33% of patients with MSMI had wall motion abnormality of the anteroapical wall. In only 8% of patients with MS and in no patients with MI and MSMI was the posterobasal segment disturbed. The anterobasal and diaphragmal wall motion showed wall motion abnormality in 16% and the septal and the posterolateral area in 17% of all patients. 78% of all patients had at least one diseased segment; motion abnormalities of the anteroapical wall (seg. 2) occurred most often whereas the posterobasal area (seg. 4) was diseased in only 4% of all patients. Ejection fraction was severely impaired (less than 55%) in 7 patients only (5 of these patients had MS) with wall motion abnormalities in more than 4 segments. There was no correlation between the extent of valve disease and occurrence and extent of wall motion abnormalities.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4024684 TI - [M-mode echocardiography study of the left atrium, precordial and suprasternal: a comparative echocardiography angiocardiography study]. AB - This study of 30 patients evaluates whether the size of the left atrium can be estimated echocardiographically with the precordial and suprasternal approach. Simultaneous imaging of the left atrium from both planes was possible in 24 patients. Angiographically, left atrial volume amounted to 107 +/- 69 ml for the minimal and 153 +/- 63 ml for the maximal left atrial size during the cardiac cycle. In each case, the diameter values of the left atrium were greatest from the suprasternal approach (p less than 0.001). All angiographic parameters were larger than the corresponding echocardiographic values (p less than 0.001). The study demonstrates that the size of the left atrium cannot be estimated reliably from biplane m-mode echocardiographic parameters. PMID- 4024685 TI - [Follow-up studies in chronic aortic insufficiency]. AB - In order to study the course of chronic aortic regurgitation 17 patients with various degrees of aortic valve incompetence were investigated twice with a time interval of 1.5 +/- 0.4 years. The following parameters were evaluated: NYHA class; electrocardiographic sum of the largest R-wave in V4-V6 plus the largest S wave in V1-V3 (RS index); echocardiographic left ventricular end-diastolic diameter (EDD); roentgenographic heart volume (HV); scintigraphic left ventricular end-diastolic volume (EDV), regurgitated blood volume (RBV) and ejection fraction (EF). During the period of observation functional deterioration occurred in 5 cases, all suffering from moderate to severe aortic regurgitation. While EF did not change significantly (55 +/- 12% vs. 55 +/- 11%), all other parameters showed a significant increase: RS index 5.4 +/- 1.4 mVolt to 6.0 +/- 1.7 mVolt (p less than 0.01); EDD 6.3 +/- 0.7 to 6.8 +/- 0.9 cm (p less than 0.001); HV 1017 +/- 151 ml to 1099 +/- 261 ml (p less than 0.01); EDV 371 +/- 131 ml to 441 +/- 175 ml (p less than 0.001); RBV 117 +/- 57 ml to 151 +/- 77 ml (p less than 0.001). Cases with functional deterioration showed a higher initial EDV and EDD (487 +/- 143 vs. 322 +/- 93 ml, p less than 0.05; 7.1 +/- 0.7 vs. 6.1 +/- 0.5 cm, p less than 0.01). The increase of HV, EDV and RBV during the time of observation was higher than in the remaining patients (166 +/- 137 vs. 39 +/- 95 ml, p less than 0.05; 133 +/- 75 vs. 44 +/- 29 ml, p less than 0.01; 66 +/- 22 vs. 22 +/- 31 ml, p less than 0.01). On average it was less pronounced in cases with mild initial left ventricular dilation than in those with marked dilation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4024686 TI - [Balloon atrioseptostomy in 2-dimensional echocardiography]. AB - Two-dimensional echocardiography allows complete evaluation of transposition of the great arteries including additional malformations. Pressure recordings and oxymetry are without indicative value in sick and hypoxic neonates and cardiac catheterization is therefore merely therapeutic (balloon atrial septostomy). In addition balloon atrial septostomy can be performed under echocardiographic control only. This procedure saves time and costs, avoids the risks of X-ray exposure and angiocardiography and can safely be performed in the pediatric intensive care unit. Five newborn babies with transposition of the great arteries were treated with this method. PMID- 4024687 TI - [Rational use of "laboratory" diagnosis from the viewpoint of the clinician]. PMID- 4024689 TI - Changes in enzyme activities in urine in children with renal diseases. PMID- 4024688 TI - [Procedure-reliability studies on radioimmunologic pancreatic glucagon determination]. PMID- 4024690 TI - [Usefulness of the biochemical monitoring of patients in critical conditions]. PMID- 4024691 TI - [Isolation and immunologic determination of apolipoprotein C-II and C-III in human serum]. PMID- 4024692 TI - [Thoughts on pediatric rapid diagnosis]. PMID- 4024693 TI - [Improvement of suction equipment for the Spekol suction attachment]. PMID- 4024694 TI - [Purification of impure 4-nitrophenylphosphate preparations]. PMID- 4024695 TI - [Evening of test data in computer-assisted analytic measuring systems]. PMID- 4024696 TI - [Morphometric and electron microscopic studies of the differentiation process of cortical neurons and their synapses in explant cultures of the cingulate region of the rat embryo]. PMID- 4024697 TI - Development of parathyroid gland of the lizard, Calotes versicolor (Daudin). PMID- 4024698 TI - Hemopoiesis in the fetal liver of the Egyptian water buffalo (Bos bubalis). PMID- 4024699 TI - Dermo-epithelial interactions during the development of cutaneous gland anlagen in Amphibia: a light and electron microscope study on several species with some cytochemical findings. PMID- 4024700 TI - Spermatogenetic cycle in Salamandrina terdigitata (Lacepede, 1788) (Amphibia: Salamandridae). PMID- 4024701 TI - Response of Channa punctatus (Bloch) under short and long term exposure to industrial pollutants: induction of histopathology in the kidney. PMID- 4024702 TI - The effect of chronic hypovitaminosis D on the bone. PMID- 4024703 TI - Localization of chromenes and benzofurans in the genus Encelia (Asteraceae). AB - Phytochemical and microscopial analysis of leaves and stems of various species of Encelia showed a strict correlation between the presence of resin ducts and the accumulation of benzopyrans and benzofurans. Fluorescence microscopy of Encelia farinosa proved unambigously that these compounds are stored exclusively in the resin ducts and the surrounding cells. PMID- 4024705 TI - A small-angle X-ray scattering study on pre-irradiated malate synthase. The influence of formate, superoxide dismutase, and catalase on the X-ray induced aggregation of the enzyme. AB - The sulfhydryl enzyme malate synthase from baker's yeast was X-irradiated with 6 kGy in air-saturated aqueous solution (enzyme concentration: congruent to 10 mg/ml; volume: 120 microliters), in the absence or presence of the specific scavengers formate, superoxide dismutase, and catalase. After X-irradiation, a small aliquot of the irradiated solutions was tested for enzymic activity while the main portion was investigated by means of small-angle X-ray scattering. Additionally, an unirradiated sample without additives was investigated as a reference. Experiments yielded the following results: X-irradiation in the absence of the mentioned scavengers caused considerable aggregation, fragmentation, and inactivation of the enzyme. The dose Dt37 for total (= repairable + non-repairable) inactivation resulted as 4.4 kGy. The mean radius of gyration was found to be about 13 nm. The mean degree of aggregation was obtained as 5.7, without correction for fragmentation. An estimation based on the thickness factor revealed that about 19% of material might be strongly fragmented. When this amount of fragments was accordingly taken into account, a value of 7.1 was obtained as an upper limit for the mean degree of aggregation. The observed retention of the thickness factor and the finding of two different cross-section factors are in full accord with the two-dimensional aggregation model established previously (Zipper and Durchschlag, Radiat. Environ. Biophys. 18, 99-121 (1980)). The presence of catalytic amounts of superoxide dismutase and/or catalase, in the absence of formate, during X-irradiation reduced both aggregation and inactivation significantly. The presence of formate (10 or 100 mM) during X-irradiation led to a strong decrease of aggregation and inactivation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4024704 TI - Acyl chain specificity and kinetic properties of phospholipase A1 and A2 of bone marrow-derived macrophages. AB - The fatty acyl specificity of phospholipase A1 and A2 in homogenates of mouse bone marrow-derived macrophages was determined using phosphatidylcholine and phosphatidylethanolamine of different acyl chain composition. Phosphatidylcholine with arachidonoyl at position 2 was cleaved preferentially by an alkaline phospholipase A2 (pH-optimum 9.0) leading to selective liberation of arachidonic acid. In contrast, phosphatidylcholines with oleoyl or linoleoyl at position 2 were degraded mainly by an acid phospholipase A1 (pH-optimum 4-5) resulting in a conservation of these fatty acids esterified in lysophosphatides. Substrate kinetics of the alkaline phospholipase A2 revealed a 30 fold higher affinity (Km = 3.8 X 10(-7) M) for 1-acyl-2-arachidonoyl-glycerophosphocholine compared to 1 acyl-2-oleoyl-glycerophosphocholine. The kinetic data were not influenced by endogenous lipids indicating that exogenous substrates do not equilibrate with cellular lipids. These results are suitable to explain a selective liberation of arachidonic acid from a mixture of phospholipids. PMID- 4024706 TI - Prosomes are involved in the repression of viral mRNA. AB - Prosomes are small cytoplasmic RNP complexes. We present evidence that their RNA is a potential and selective inhibitor of viral mRNA translation while translation of normal cellular mRNA e.g. rabbit globin mRNA or HeLa cell mRNA is not affected. PMID- 4024707 TI - Solubilization and partial purification of a cell surface component of Leishmania braziliensis. AB - A simple procedure that allowed the extraction and partial purification of a component of 65,000 mol.wt. from the surface of Leishmania braziliensis promastigotes is described. Iodinated cell surface membrane fractions were solubilized using Triton X-100 followed by Nonidet P-40. The macromolecular components were then freed of the detergents by passage of the extracts through a column of DE52 cellulose. The component of 65,000 mol.wt. was eluted from the column with 1 m NaCl. This component in whole parasites was immunoprecipitated by sera from patients with cutaneous, mucocutaneous, and diffuse cutaneous leishmaniasis and kala-azar. None of the major surface determinants reacted with sera from normal individuals with antibovine rabbit serum. The relevance and the possible applications on the immunoprophylaxis of the disease are briefly discussed. PMID- 4024708 TI - Transmission experiments on the host specificity of Heterophyes species in 16 potential definitive hosts. AB - Sixteen different species of piscivorous mammals and birds were tried as experimental definitive hosts for Heterophyes heterophyes, H. aequalis and H. dispar. The hosts were classified in four categories, by fluke longevity, recovery and size, and the number of uterine eggs (embryonated/unembryonated): (1) Canidae and the cat were highly susceptible hosts for all three species of Heterophyes; (2) several mammals and herons showed a reduced susceptibility to infection (H. aequalis, 6 species; H. dispar, 1 species; H. heterophyes, 0 species); (3) In a group of hosts specific to each trematode, flukes were recovered up to 14 days post infection, but their uterine eggs did not become embryonated; (4) In a fourth category of hosts, chiefly Mustelidae, flukes could not be recovered. Taking also the literature into account it is concluded that man is a highly susceptible host for H. heterophyes, and that probably H. aequalis and H. dispar may reach reproductive maturity in humans also. The described wide host range of H. aequalis appears to be more typical for Heterophyidae than the comparably narrow host range of H. heterophyes. PMID- 4024709 TI - Chemotactic attraction of infective hookworm larvae of Ancylostoma caninum by a dog serum factor. AB - Infective hookworm larvae of Ancylostoma caninum showed chemotaxis on agar plates in a dog serum gradient. This chemotactic behaviour remain unaltered using an ultrafiltrated serum fraction with a molecular weight less than 500. Gelfiltration of this ultrafiltrated fraction revealed a factor with a molecular weight of 480 causing chemotaxis. The chemotactic activity of the factor was destroyed after a pronase treatment. We conclude that the factor could be a polypeptide. PMID- 4024710 TI - Human pulmonary dirofilariasis with special reference to the ELISA for the diagnosis and follow-up study. PMID- 4024711 TI - Improving outcome of aneurysmal subarachnoid hemorrhage. PMID- 4024712 TI - Shoulder joint replacement. PMID- 4024713 TI - Role of barium enema in diagnosis of acute appendicitis: case report. PMID- 4024714 TI - [Prostaglandins in various diseases in children and adolescents]. PMID- 4024715 TI - [Changes in nitrogen metabolism in the brain in the post-hypoxic period]. PMID- 4024716 TI - [Intrauterine lesions of the brain]. PMID- 4024718 TI - [Current problems of pediatric allergology]. PMID- 4024717 TI - [Metabolic control of arterial blood pressure during oxygenation in the early neonatal period in full-term infants born to healthy women and to those with late pregnancy toxemia]. PMID- 4024719 TI - [New data on the problem of mucoviscidosis]. PMID- 4024720 TI - [Current principles of antibacterial therapy of bronchopulmonary diseases in children]. PMID- 4024721 TI - [Total plethysmography in the evaluation of ventilatory insufficiency in chronic pneumonia in children]. PMID- 4024722 TI - [Functional evaluation of granulocytopoiesis in children by the agar culture method]. PMID- 4024723 TI - [Development of the immune system and the state of immunological reactivity in pathological processes in children]. PMID- 4024724 TI - [Endocrine disorders in convulsive states in children]. PMID- 4024725 TI - [Clinico-biochemical parallels in closed cranio-cerebral trauma and its sequelae in children]. PMID- 4024726 TI - [Possible treatment of metastases of breast cancer to the bones]. PMID- 4024727 TI - Expression and regulation of the vaccinia virus thymidine kinase gene in non permissive cells. AB - The expression and regulation of the vaccinia virus (VV) thymidine kinase (tk) gene was examined in two non-permissive cell lines, CHO and MDBK, which restrict VV development at different stages of the viral replication cycle. The VV tk gene was expressed in these two cell lines with kinetics similar to a fully permissive cell line BSC40. These results are consistent with the hypothesis that inhibition of tk mRNA translation by another viral early gene product is a normal component of the overall strategy employed to express and regulate the VV tk gene during a productive infection. PMID- 4024728 TI - Sequence of the nucleoprotein gene of influenza A/parrot/Ulster/73. AB - The nucleotide sequence of the nucleoprotein (NP) gene of the avian influenza A virus strain A/parrot/Ulster/73 (H7N1) has been determined. The gene (RNA segment 5) consists of 1565 bases. The only large open reading frame of the complementary RNA codes for a protein of 498 amino acids. A comparison of its sequence with that of three other influenza virus NPs shows that the NP of the parrot Ulster strain, although closely related to the NP of the other avian strain (A/FPV/Rostock/34), is definitely more closely related genetically to the NPs of the two human influenza strains, A/PR/8/34 and A/NT/60/68 than that of FPV. This raises the question how far the NP gene can cross the species barrier by reassortment and become adapted by mutation to the new host. PMID- 4024729 TI - Natural heterogeneity of shape, infectivity and protein composition in an influenza A (H3N2) virus preparation. AB - Influenza A (X31) virus was purified over a zonal sucrose gradient. The resulting gradient fractions were examined by electron microscopy, HA and infectivity titrations and gel electrophoresis. The fractions containing a homogeneous suspension of spherical particles had the highest infectivity per amount of viral protein and a much higher HA:M ratio than the unfractionated preparation. These results explain differences in the proportions of HA and M protein we have reported elsewhere on monodisperse virus suspensions compared with earlier measurements on crude suspensions. PMID- 4024730 TI - [Lateralization of visual perception of letters during reverse masking]. AB - Identification by healthy subjects of single letters in conditions of backward masking was studied at lateralized presentation of stimuli. Both at dichoptic and unilateral presentations, the letters are identified better if they are presented in the left visual field, i.e. addressed "directly" to the right hemisphere. It is suggested that the data obtained result from the specificity of hemispheres' cooperation under difficult conditions of visual-spatial stage of information processing. PMID- 4024731 TI - [Electroencephalographic and motor indices of perception and possibility of information transfer from stage 2 to the REM phase of human sleep]. PMID- 4024732 TI - [Evaluation of the professional qualities of operators working with computer displays]. AB - The influence of spatio-temporal factors (spatial heterogeneity of distribution of the numbers sought for in the matrix of data, processes of learning and development of fatigue, periodic attention oscillations) of the character of solving the task of searching the numbers in a matrix of 176 three-figure numbers (16 lines, 11 columns) was studied in 39 operators. The possibility was shown to use the characteristics obtained for evaluation of professionally important abilities of an operator working at the display. PMID- 4024733 TI - [Systems analysis of the flow of associations in healthy subjects and patients with mental disorders]. AB - By means of mathematical apparatus of a model of frequency lexical structure the structure of repetitions was studied in association flows of 10 healthy persons, 10 patients with sequelae of closed craniocerebral injury, and 10 schizophrenics. In comparison to healthy persons in those after the brain injury the number of repetitions was increased and the distances between the first and the last use of the repeated words were significant. In schizophrenic persons the repetitions of the words were situated at the local portions of association flows. The structure of repetitions in these association flows was close to that of the usual connected text by the general quantitative norms. Such structure of repetitions should be explained by the presence of a parasitical system of connections between the words equivalent by its strength to usual rational connections in a meaningful text. PMID- 4024734 TI - [Significance of presetting an analyzer system in discriminating light intensity in the cat]. AB - EEG and behavioural reactions were studied at the action of signal and nonsignal light flashes. The minimal time of stimulus exposition necessary for preserving differences in EEG activation reactions to nonreinforced stimuli of different intensity (in a diapason from 3.5 to 250 lk) was shown to exceed 1 s. After giving the signal meaning to the flashes the minimal time of stimulus exposition when the animals were capable to discriminate intensity of the flashes (in a diapason from 3.5 to 30 lk) just at the first presentation, was equal to 0.1 s. Decrease of the minimal time of stimulus exposition necessary for discrimination of the light signals was supposed to be stipulated by their biological significance and presetting of the analyzing system being organized by preliminary learning a crude analysis of stimuli. Discrimination of the light stimuli of short duration was impossible without such presetting. PMID- 4024735 TI - [Effect of destruction of the septum and hippocampus on the shuttle-box avoidance conditioning of the rat]. AB - Total destruction of the septum, the dorsal hippocampus (DH), or the lesion of the DH combined with that of the medial septal nucleus in rats was shown to facilitate elaboration of conditioned avoidance responses in a shuttle-box due to an increase of general excitability of the animals, and to cause significant impairment of internal inhibition formation. Lesions of the medial or the lateral septal nuclei as well as a combined lesion of the DH and the lateral septal nucleus had no significant effect on conditioning and internal inhibition elaboration. Therefore the septo-hippocampal connections had different functional directions during active defensive behaviour. PMID- 4024736 TI - [Interhemispheric asymmetry of "emotional resonance" in the rat]. AB - Hemispheric asymmetry of "emotional resonance" elaborated by the method of P.V. Simonov was studied in Wistar rats. Inactivation of hemispheres was carried out by means of spreading depression. When using as "victims" and "recipients" the animals of the same sex, lateralization of emotional resonance was found to depend upon the velocity of reaction elaboration. In rats rapidly elaborating avoidance reaction the right hemisphere dominated during its performance and so did the left one in animals learning after additional training. When using the animals of different sex as "victims" and "recipients", the right hemisphere dominated in "emotional resonance" performance. Hemispheric asymmetry of "emotional" resonance was more expressed in males than in females. PMID- 4024737 TI - [Regional features of the electrical activity of the neocortex in the dog over a wide range of frequencies]. AB - Autospectral characteristics (ASC) of potentials of different neocortical areas of dogs in a state of quiet wakefulness were studied in a wide frequency band (1 100 Hz) by means of correlation-spectral analysis. A transition from evaluation of the mean power tendencies to a construction of distributions of different power levels for each of five arbitrarily chosen frequency bands permitted to reveal regional differences in ASC of each animal as well as interindividual EEG distinctions. The regional differences observed in all frequency bands (though not equally expressed) including the higher ones indicate not only the informativity of high-frequency components of electrical neocortical activity but also their neuronal origin. PMID- 4024738 TI - [Morphophysiologic study of reticulo-cortical pathways in the rabbit]. AB - The character of functional connections between the midbrain reticular formation (RF) and the neocortex was studied in rabbits. Unit activity was recorded in sensorimotor cortex by extracellular microelectrode during RF stimulation. Short latency neuronal reactions were found presumably identified as monosynaptic responses. Results of the studies of anterograde degeneration of myelinic fibers and axonal terminals after electrocoagulation of the RF carried out with the help of electronic microscope allowed to suppose that there were few (less than 0.5 per cent) monosynaptic connections between the RF and the sensorimotor cortex. The main forms of direct connections between these structures were axo-dendritic (situated at the dendritic trunk) and axosomatic synapses at the neurones of the sensorimotor cortex. PMID- 4024739 TI - [Effect of ethanol on the activity of neurons of the ventromedial and ventrolateral hypothalamus of the rabbit]. PMID- 4024740 TI - [Relation between solving an extrapolation task and parameters of the open field in the rat]. PMID- 4024741 TI - [Reflection of the state of drinking motivation in the activity of neurons of various brain structures in the rabbit]. PMID- 4024742 TI - [Interaction between portions of the receptor membrane of the nerve cell in the generation of spike activity in the crayfish]. PMID- 4024743 TI - [Asymmetry in direction of movement in the Myrmica rubra ant during labyrinth training]. PMID- 4024744 TI - Alcohol policies in national health and development planning. Including a summary of the technical discussions held during the thirty-fifth World Health Assembly, 1982. PMID- 4024745 TI - [Metal concentrations in fishes of the Rednitz River]. AB - We investigated 39 fish species (eel, brown trout, chub, carp bream, roach, perch, pike etc.) from the river Rednitz (North Bavaria) for content of the metals mercury, lead, cadmium, arsenic, selenium and zinc. The residue tolerance level for mercury (1 mg/kg) and the standard value of the Federal Public Health Office for lead (0.5 mg/kg) and cadmium (0.05 mg/kg) have not been exceeded in any case. Because a small selenium concentration gives protection against the toxicity of mercury, we also have calculated the molar selenium-mercury correlation in the fish-samples. PMID- 4024746 TI - [Analysis of whole gliadin from untreated and heat-treated flour with phase inversion high pressure liquid chromatography]. AB - The gliadins from various wheat flours either untreated or heated (baking, cooking, roller-drying, extrusion-cooking) were extracted with 70% ethanol and analysed by RP-HPLC. When flours are heated below 80 degrees C the chromatograms showed no significant change. At temperatures about 80-90 degrees C a peak appeared in all samples (with the exception of durum wheat) at a retention time of 35 min (peak 35) or, if already present, become more pronounced. A further increase in temperature or treatment time resulted in an increase in this peak whereas the peaks of the more strongly bound gliadins slowly disappeared. In the gliadins of the bread crust the amount of peak 35 decreased again. Similarly, changes were observed in the distribution of the apparent molecular weights of gliadins from heated flours by using gel electrophoresis (SDS-PAGE). At temperatures about 80-90 degrees C the bands between 50-62 kD (under reducing conditions) appeared or become stronger. Their intensity increased with increasing time and treatment temperature whereas the lower molecular weight bands slowly disappeared. Peak 35 may be useful as an indicator of gliadin in heat-treated "gluten-free" foods. PMID- 4024747 TI - [Quinic acid lactone in coffee]. AB - Quinic acid and its lactone (quinide) have been determined in coffee by capillary gas chromatography. No quinide could be detected in 14 green coffee's. After steaming of 4 green coffee's the content of quinic acid was always higher, but no quinide had been formed. During roasting, the latter can be detected when roasting loss exceed 6.5%. It increases approximately proportionally with quinic acid and amounts to 50% of the latter at 22% roasting loss. Both constituents decrease at unusual high roasting loss. In 13 commercial blends of roast coffee 2.4-6.4 g/kg quinide and 8.7-16.6 g/kg quinic acid were present. Especially high values were found in one Espresso type blend and high values in steamed and decaffeinated coffee's. In 11 commercial coffee extracts 2.0-23.2 g/kg quinide and 24.6-36.4 g/kg quinic acid were determined. At higher extraction yield, more quinic acid and quinide is formed, but at very high extraction yield the content of quinide is diminished. During holding of coffee brews at elevated temperature, quinide is slowly hydrolysed. PMID- 4024748 TI - [Ochratoxin A in pork kidneys--description of a method]. AB - A rapid procedure for the isolation and clean-up on a silica gel column is described for the determination of Ochratoxin A from pork kidneys. The detection limit is 0.3 microgram/kg. PMID- 4024749 TI - [Suffocation death by occlusion of the airways with sand]. AB - Eleven cases are reported in which death occurred because of suffocation as a result of occlusion of the respiratory tract by sand (without thoracic compression: 3 cases) or being buried alive (8 cases). Two tables demonstrate the findings and circumstances in the events. Three cases are described in detail. A 22-year-old woman was manhandled by blows and kicks to the head and neck. She became unconscious and her head and neck were covered by a layer of sand so that she suffocated. A 42-year-old man was smothered, while unconscious, in a prone position with his face in the sand, after hard blows to the head by two culprits. A 17-year-old girl finally died by chocking. Previously the culprit had pressed her face into the ground, so that she aspirated particles of soil. The question of vital reactions during aspiration of sand was investigated by microscopic examination of the content of the air passage and by destroying parts of the lungs by sulphuric acid. Minimal aspiration of sand occurred in all cases. Although the postmortal remains were left in the ground, there was no postmortem penetration of sand into the air passage. Histological examinations were carried out to support the diagnosis of violent suffocation. In some cases, there were remarkable findings (mobilization of alveolar cells, hepatocelullar hydropic degeneration), but there were no typical or unanimous findings that pertained to all cases. PMID- 4024750 TI - [Reconstruction of the sitting position in automobiles by microtrace analysis]. AB - Three car accidents are described in which microtrace analysis was of special significance in the clarification of the seating positions. In all three cases the occupants were under the influence of alcohol. In each case the accident occurred at night and without witnesses. The pattern of injuries in two cases was non-specific. In the first case, no fiber traces were visible to the naked eye; in the other two the fibers were recognizable to the naked eye after close examination. In all three cases, the seating position was ascertained by means of fiber trace analysis. PMID- 4024751 TI - [Effects of fauna on cadavers and microbial saprophytes on blood group findings on human tissues]. AB - The investigation of postmortem human tissue, exposed to the influence of flies and their maggots, has shown in general that there is a drop in ABO blood-group activity due to the secretive action of the anterior intestinal gland of the larva. In addition, the phenomenon of acquired heterogeneous blood-group-specific substances was observed. By analogy with the findings in mummy tissues, the postmortal invasion of foreign bacterial and fungal blood-group-active material is discussed as a cause of erroneous serological diagnosis in bones. Acquisition of foreign serological activity through plant saprophytes was detected in a bone sample infested with algae. In different subfossil bone samples, blood-group activity was evident in the more decomposed areas, while in the better preserved parts of the bony substance, negative reactions were obtained. PMID- 4024752 TI - [Characterization of microtraces of blood]. AB - The stains produced from micro-blood-drops (blood volume 0.2 microliter) on different substrate materials were examined with respect to morphological characteristics. Micro-stains made on paper showed the same general pattern as larger (macro-)bloodstains on the same substrate. The use of shirt material as substrate, however, resulted in differences in the stain pattern, particularly a greater variation within otherwise identical series. In addition when the angle of the bloodstains was acute, a variable number of smaller stains became detached. In these cases definite criteria can still be found for a description of bloodstains and for estimating the approximate angle of impact. PMID- 4024753 TI - FELASA--Federation of European Laboratory Animal Science Associations. Proceedings from the 2nd FELASA Symposium. Malmo, Sweden, June 16-21, 1984. Abstracts. PMID- 4024754 TI - [Comparative studies of sudden and non-sudden death due to coronary disease]. AB - A comparative study of patients dying acutely and non-acutely from coronary heart disease was performed. The average age of the acute death group was significantly lower than the non-acute death group. There is no difference between the average age at death of the latter and that of those persons who died from non-coronary causes. The majority of patients with chronic ischemic heart disease (CIHD) died a sudden death. This proportion is especially high among males under 50. Taking into account the different manifestations of chronic ischemic heart disease most males and females with sudden death died as a consequence of acute coronary insufficiency. In the group of non-acute coronary deaths, acute and recurrent myocardial infarction dominated as the cause of death. Coronary thrombosis was less frequent in the acute compared to the non-acute death group. There was no significant difference in the frequency of cardiac rupture between the two groups. Severe coronary arteriosclerosis was substantially more frequent in the acute group compared with the non-acute. PMID- 4024755 TI - [Pathological anatomy and histology as well as pathogenesis of leg thickness in piglets]. AB - Leg thickness in piglets was found to be an autosomal recessive defect resulting in a primary developmental disturbance of the periosteal and connective components of the soft tissues of the fore- and, less frequently, hindlegs. Histologically there is periosteal thickening with periosteal proliferation of woven bone spiculae and also of myxoid elements of the soft tissue between bone and skin. Similar entities are not known in the human literature. Analogies with human hereditary congenital elephantiasis and pes equinovarus are incorrect. PMID- 4024756 TI - [Hemorrheological changes in microcirculation caused by fats of different dosage, composition and mode administration]. AB - Descriptions of the nature and pathogenesis of disturbances of the microcirculation induced by intravenous infusion of a triglyceride emulsion or by daily oral administration of a cholesterol-in-oil suspension are different and partially contradictory in the medical literature. Hyperlipemic disturbances of the microcirculation are characterized by a general decrease in the rate of flow reflected in all parameters of flow in the terminal blood vessels including a rise of the number of capillaries temporarily functionally isolated from the circulation and by an increase in capillary plasma skimming. The degree is dependent upon the amount of administered fat and on lipid levels. The disturbed capillary perfusion can be attributed to various rheological mechanisms. The hemodynamical relevance of the short-time hyperlipemia produced by intravenous infusion of a fat emulsion and the enduring hyperlipemia produced by the daily oral administration of a cholesterol-in-oil suspension differ. Some of the capillary-rheological bases of these differences are discussed. PMID- 4024757 TI - [Functional therapy in primary unstable injuries of the thoracic and lumbar spine. Indications and limits]. AB - There are good results in the functional conservative treatment of the primary stable lesion of the thoracic and the lumbar part of the spine. Late results show that traumatic deformation can be compensated by the spine and by trained muscles. Segmental mobility can be generally neglected. Real late instabilities are very seldom. Static complaints caused by left deformation are important especially if the spine was previously damaged. Then, primary or early secondary operative reposition, replacement and segmental spondylodesis are indicated. PMID- 4024758 TI - [Indications and results of early functional vertebral fracture treatment]. AB - Early functional treatment was administered to 213 patients with stable compression fractures of thoracic and lumbar vertebrae between 1975 and 1982. Physiotherapy was carried out according to a uniform schedule. The patients were mobilized after an average of 6 days; hospitalization lasted 2 weeks on an average. Control examinations of 82 of these patients revealed only a slight union of compressed vertebral bodies (on an average, 7% of the initial height), which correlated with the primary compression and the patient's age. Remaining functional restriction of the spine and subjective complaints did not correlate significantly with the extent of vertebral compression. PMID- 4024759 TI - [Treatment of fractures of the cervical spine with external halo fixation]. AB - 15 serious injuries of the cervical spine were treated by Halo-fixation devices. Practical procedure as well as advantages in clinical application are dealt with. This method seems to be a good alternative to surgical stabilisation. PMID- 4024760 TI - [Treatment of tibial shaft fracture in the area of the large medullary cavity--an indication for intramedullary nailing? Results of intramedullary nailing and comparison with concurrent treatment procedures]. AB - Nailing has become the major method of treating lower leg fractures: though there are still different opinions how to treat lower leg fractures localized between the proximal-middle and middle-distal third as well as in the second and fifth/sixth. Following our own experiences with 192 lower leg nailings in that sphere we report the results in order to demonstrate the efficiency of nailing in comparison with the traditional way of conservative treatment and plate osteosynthesis. PMID- 4024761 TI - [Carpal tunnel syndrome induced by aseptic necrosis of the scaphoid bone]. PMID- 4024762 TI - [Traumatic scaphoid bone malposition of the hand]. PMID- 4024763 TI - [Unusual course of osseous metastasis of hypernephroid carcinoma]. PMID- 4024765 TI - [The need for joint irrigation following hemarthrosis puncture]. PMID- 4024764 TI - [Selective laparotomy and value of peritoneal irrigation in penetrating abdominal injuries]. PMID- 4024766 TI - [Severe infections in pregnancy and the puerperium--prevention and therapy]. AB - Serious infections during pregnancy and puerperium hold the second place as a cause of maternal mortality. The most dangerous infections are chorioamnionitis and puerperal infections especially after cesarean section. Their prevention and management are dealt with. PMID- 4024767 TI - [Results following gastrectomy and its relation to tumor stage in stomach cancer]. AB - 88 patients suffering from gastric cancer underwent total gastrectomy. The late results were clearly dependent on the stage of the tumour. In cases of stage T1 and T2 the 5 years survival rate amounted to 86%, in cases of T3 and T4 however, only to 4%. In cases of M0 50% of these patients lived longer than 5 years, in patients with lymphatic spread this percentage came up to 8.7 only. The postsurgical mortality rate was 19.3 on an average with an increase in larger tumours. For improving the prognosis the authors recommend total gastrectomy even in cases of the gastric tumour having a smaller extent. PMID- 4024768 TI - [Surgical complications in the area of the bile ducts from the forensic viewpoint]. AB - In a period of 10 years there were 21 cases of iatrogenic lesions of the extrahepatic bile ducts following cholecystectomy (n = 19). In 2 cases of partial gastrectomy an expert's opinion was taken. 8 patients out of 21 came to death. The striking fact is that in 7 cases the removal of the gallbladder had been performed in retrograde direction. PMID- 4024769 TI - [Perforation of Crohn disease in the free abdominal cavity]. PMID- 4024770 TI - [The appendix as a foreign body reservoir]. PMID- 4024771 TI - [A practice phantom for learning rectal digital examination]. PMID- 4024772 TI - [Microbial colonization of coating and building materials in contact with drinking water. 11. Long-term studies of a drinking water reservoir with polyester isolation]. AB - Building materials of drinking water reservoirs can support a microbial growth as shown in former communications. A new case is presented, where the microorganisms used the polyester isolation as carbon source. The isolation was installed between two concrete layers of a drinking water reservoir. The organic substances were identified by chemical analyses. PMID- 4024773 TI - [Qualitative and quantitative determination of bacterial populations in an aquatic environment. 7. Development of bacterial growth on raw materials exposed to potable water]. AB - Refined steel plates coated with different materials that contained available organic compounds led to a microbial growth on the surface. Even plastics and bitumen which were used in the sphere of drinking water showed after an exposure time of three months up to 192 ml slime per square meter. The number of viable bacteria within the Aufwuchs was in the range of 10(7) cfu/ml. The production of slime increased with time. The relation of carbohydrate and protein content significantly changed from 2 at the beginning to 30 after 12 months of incubation the bitumen coating test plates. This indicates an increase synthesis of carbohydrate containing extracellular polymeric substances during the late phase of growth. The bacteria isolated from the Aufwuchs mainly belonged to the genera Pseudomonas, Flavobacterium, Acinetobacter, Caulobacter, sheated bacteria and other gramnegative physiologically nonreactiv roads. During exposure of the plates the relation changed within the bacterial communities of the main groups. Comparing the bacteria communities of inlet and outflow water it became evident that the later one was influenced by bacteria of the Aufwuchs. PMID- 4024774 TI - [Qualitative and quantitative determination of bacterial populations in an aquatic environment. 8. Variation of the species spectrum during a drinking-water treatment process]. AB - Water treatment processes such as aeration, gravel filtration, ozonation, activated-carbon filtration and chlorination causes variation in the number of bacteria as well as the development or die off of specific species. The number of bacteria was always reduced to a large extent if ozone or chlorine were applied whereas after filtration process often an increasing number of bacteria could be observed in the effluent. Despite of the differing bacterial counts a reduction of the variety of species was found during all treatment process. Whereas the raw water contained a heterogeneous spectrum of copiotrophic and oligotrophic bacteria the treated water contained mainly slow growing oligotrophic bacteria which didn't express any physiological activities. PMID- 4024775 TI - [Microbiological studies of groundwater polluted with hydrocarbons. 2. Determination of bacterial in vitro activity]. AB - The injected water and the groundwater withdrawn by the E-wells contained bacteria with higher 'in vitro'-total activity (30-50%) than the groundwater taken from the middle part of the flushing area. The determination of single activities resulted in a similar distribution of bacterial communities. Denitrifying and nitrate-reducing bacteria were present in the polluted groundwater (10-100% of isolates). After transforming these values in CFU/ml they correspond to the MPN/ml of both groups. Furthermore bacteria were found, which could use hydrocarbons as their only carbon source under aerobic and anaerobic conditions; there were different percentage of hydrocarbon-degrading bacteria in the groundwater of the three sampling points. Totally 2-70% of all isolates were aerobe hydrocarbon-degrading bacteria, 1-12% nitrate-reducing and 1-13% denitrifying hydrocarbon-metabolizing bacteria. PMID- 4024776 TI - [Use of fish cell cultures for toxicity determination in order to reduce and replace the fish tests]. AB - Dispersion of liver tissue from rainbow trout at 10 and 25 degrees C resultet in cells which were cultivated in vitro at 20 degrees C regularly. Using this method a cell line (R1) has been established useful for testing the toxicity of chemical substances and waste water. The toxicity of samples influenced the morphology, growth and the living duration of the cells. These parameters gave a clear answer about the toxicity of samples testet in 1-12 h. The tests on the vitality of cells (using trypan blue) and the release of LDH did not show an agreement with the cytotoxicity in all cases. From 106 samples of waste water were 53.8% cytotoxic but only 35% showed a toxicity for fish. 93.44% of 61 toxic samples of waste water showed cytotoxicity, only 60.65% of the samples were fish-toxic. According to the results obtained it is concluded that fish cell tissue cultures are useful tools for determination of the toxicity of chemical substances and waste water. Compared with the fish test the cytotoxicity test ist more sensitive and it reduces the material, time and money needed. PMID- 4024777 TI - Mycobacteria in semi-public swimming-pools and whirlpools. AB - The presence, densities and species distribution of atypical mycobacteria were assayed in samples from swimming-pools in semi-public areas (hotels, recreational parks and camping grounds) and from whirlpools (in sauna institutes, fitness clubs and recreational parks). Tap water used to supply these pools was also investigated. Mycobacteria were frequently detected in all types of samples, the numbers in whirlpools on the average being about ten times higher than those in swimming-pools and tap water. Mycobacterium gordonae was the predominant species in all samples. Special attention was given to the possible presence of opportunistic pathogenic mycobacteria. M. marinum was not detected in any of the samples; M. kansasii was recovered 3 times from whirlpools only. M. avium and the M. fortuitum-M. chelonei complex were found in both types of pool samples but in highest densities in whirlpools. Mycobacterial densities exhibited a significantly negative association with the concentration of hypochlorous acid 1.0 mg/l being required to assure low levels in the bathing water. There was also a negative association with redox potential but positive associations with total aerobic colony count at 37 degrees C, ammonium and total Kjeldahl nitrogen (in swimming-pools only). No association was found with temperature, potassium permanganate consumption, total coliforms, Pseudomonas aeruginosa or Staphylococcus aureus. PMID- 4024778 TI - [Health risks due to long-term stress--night work as an example]. AB - Multiple matched cases of shiftworkers, dayworkers and drop-outs, (N = 301) were split into four groups corresponding in age and years at work. Data concerning different parameters of health and wellbeing were collected by means of medical case histories, check-ups, questionnaires and interviews. Time contingent effects of health deterioriation were analysed. In terms of an overall score ("Health Score") in shiftworkers health was found to decrease with age markedly; the difference to dayworkers got significant from the 12th year of work exposure onwards. This finding can be ascribed to a high rate of sleep disturbances and a pronounced reduction of wellbeing (already present in younger workers) as well as to a significant increase in morbidity concerning gastrointestinal and cardiovascular ailments. Corresponding rates of doctor's consultations and drug intake increased with age and work exposure. Subjective ratings of work conditions suggest marked mental and emotional stress components. In dayworkers a destabilization of health was found which was marked for the middle age; the health score, however, was still significantly better than that of shiftworkers in all age classes. There was evidence of an excess rate for respiratory illnesses. In drop-outs less adverse conditions of health and wellbeing than in shiftworkers were found. But health was more deteriorated than in dayworkers. Having dropped out of shiftwork means an improvement of gastrointestinal and nervous symptoms; the cardiovascular disorders, however, remain high. PMID- 4024779 TI - [Effect of the oral beta-mimetic drug clenbuterol (Contraspasmin, Spiropent) and orally and intravenously administered Partusisten on the rheobase]. AB - Clenbuterol (Contraspasmin, Spiropent) was used to treat threatened delivery in a dosage of three times 0.02 mg per day because of its beta-mimetic effects and the halflife time for elimination of 34 hours. We examined the effect of Clenbuterol on the maternal rheobase as a factor to estimate the influence of this drug on neuromuscular structures of maternal organism. After the first oral application of Clenbuterol we found a significant decrease in this value and after second and third application a distinct fluctuation. This fact shows besides the positive beta-mimetic properties the side-effects on the vegetative nerve system and on neuromuscular structures of the female body. PMID- 4024780 TI - [Supplementation of antenatal cardiotocography (nonstress test) by nipple self stimulation]. AB - Self-stimulations of nipples were performed in 155 late pregnant women in connection with antenatal cardiotocography (nonstress test). Cardiotocographs were interpreted using an own score. Uterine contractions could be produced by nipple stimulation in 111 women (71.6 per cent). In 13 cases with score 6 to 8 these contraction contributed to explantation of fetal condition. In additional 11 cases with score 9 to 10 the attention was focussed to the reduced fetal or placental capacity by the suspect cardiotocogram. In this group frequency of caesarean section was increased significantly. In cases with successful nipple stimulation the rate of labour induction with effect was higher. Oxytocin liberation by nipple stimulation may be regarded as endogenous oxytocin stress test. This simple procedure which can be done quickly and without danger is supposed to be a good supplement to nonstress test. Its reliability can be improved and the success of induction of labour estimated. PMID- 4024781 TI - [Pulmonary edema under tocolytic therapy]. AB - A case of pulmonary edema during tocolytic therapy with beta-mimetic drugs is demonstrated. Isotonic hyperhydration is suspected as the reason favoured by oliguria and hypocalcemia. Diagnostic and therapeutic consequences are discussed. PMID- 4024782 TI - [Compatible receiver insert for telemetric monitoring of labor]. AB - A receiver-insert for telemetric monitoring of childbirth, which is compatible with the monitoring system of VEB Messgeratewerk Zwonitz, is presented. PMID- 4024783 TI - [Cardiotocography--practice. Case 9]. PMID- 4024784 TI - [Toward a single inter-disciplinary classification of cranio-cerebral injuries]. AB - The article presents clinical criteria of the diagnosis of concussion, contusion and compression of the brain in the acute period of a craniocerebral injury. The authors specify the major signs of a moderate and deep stun, sopor, as well as moderate, deep and coma de passe. Unified evaluations of the severity of the state of a patient with a craniocerebral injury are described. PMID- 4024785 TI - [Variants of the clinical course of the late period of military closed craniocerebral injuries]. AB - As a result of a comprehensive psychoneurological examination of 160 war veterans who had sustained a cranicocerebral trauma of a mild or moderate degree during the Great Patriotic War, the authors identified 3 variants of the clinical course of its long-term period: (1) late (at the age of 45-59 years), protracted (of many years) decompensation of a complex (polymorphic) posttraumatic neuropsychic defect; (2) a comparatively early (by age) and accelerated development of cerebral atherosclerosis and arterial hypertension with unstable compensation of posttraumatic cerebral, predominantly vegetative-angiodystonic disorders; (3) the prevalence in the clinical picture of the disease of marked manifestations of chronic cerebrovascular failure or stable sequels of brain stroke in the presence of individual reduced psychopathological posttraumatic symptoms. The article also presents electrophysiological, biochemical and psychological changes characteristic of each variant of the course, which should be taken into consideration in making the diagnosis and predicting the clinical and employment related outcome. PMID- 4024786 TI - [Volume dynamics of contusion foci of the cerebrum]. AB - Of 740 patients with severe contusions of the brain a group of patients with expansion of the contusion foci was differentiated. In 31.8% of the patients, the contusion foci were localized in the polar-basal portions of the frontal and/or temporal lobes and in 2.5% of patients on the convex surface of the large hemispheres and penetrated into the white matter. Clinical variants of the course of expansion processes of contusion foci are described. The craniographic, echoencephalographic and angiographic characteristics of the damaged brain are also presented. Expansion of contusion foci of the large hemispheres is documented pathomorphologically. A correlation was found between the manifestations of expansion of the contusion foci and their structural characteristics. PMID- 4024787 TI - [Vibration sensitivity in traumatic lesions of peripheral nerves]. AB - Using a tonal audiometer, the parameters of vibrational sensitivity (in decibels) were investigated in 50 patients with traumatic damage to the peripheral nerves of the extremities. The results reflected the severity of neural damage and also the degree of the restoration of neural functions following surgical or conservative treatment. PMID- 4024788 TI - [Restoration of discrimination sensitivity after suturing nerves of the upper extremity]. AB - Having examined the discriminational sensitivity with Weber's dividers in 244 patients 1-10 and more years after epineural suture of the median, ulnar and palmar digital nerves, the authors established that this type of sensitivity restored slowly, incompletely and rarely. Discrimination of two points was better restored after suture of the palmar digital nerves, it was worse after suture of the median nerve and was the worst after suture of the ulnar nerve. The factors adversely affecting the restoration of discriminational sensitivity included a high level of damage (upper arm, the upper third of the forearm) and a considerable delay with surgery. PMID- 4024789 TI - [Electromyographic characteristics of recovery of motor function in patients with lesions of the cervical division of the spinal cord]. AB - Electromyographic examination used for determining spontaneous activity of the muscles in patients with an injury at the level of C3-C6 showed that at the first stage the most significant sign was the presence of at least weak activity in the muscles of the lower extremities. This was usually a precursor of the successful restoration of motor functions and indicated the smallest volume of the injury and the absence of complications. At the later stages of treatment of these patients EMG revealed considerable activity in all major muscle groups ensuring walking and the maximum independence of the patient. PMID- 4024790 TI - [Significance of evaluation of the functional status of the vessels and the heart after surgical treatment of injuries of the cervical and thoracic levels of the spinal cord]. AB - An analysis of the clinical and neurological data on 52 patients with spinal cord lesions at the level of C4-Th8 segments and their comparison with the function of the vessels and heart have shown that the severity of these patients' condition is determined by disorders of the regulation of the vascular tone, the development of arteriolar hypotonia, disturbances of the regulation of cardiac activity and pulmonary ventilation disorders. The sympathetic regulation of the vessels and heart undergoes phasic changes which should be taken into consideration in the anesthetic-resuscitative support of surgical intervention. This helps decrease the mortality rate and improve the results of treatment. PMID- 4024791 TI - [Diagnostic significance of the spinal-brain stem polysynaptic reflex and the period of inhibition]. AB - Electrical stimulation of the radial nerve associated with voluntary contraction of the shoulder girdle inhibited bioelectrical activity not only in the muscles of the hypothenar but also in the proximal muscles. In resting muscles, such stimulation elicited a reflex response with a large latent period. With weak voluntary tension stimulation elicited a reflex response while in the presence of considerable contraction the reflex response merged with bioelectrical activity, with a clearly demonstrable subsequent period of inhibition. The current viewpoint about the antidromal blockade of the segmental motoneurons is debated. It is suggested that the polysynaptic reflex and the inhibition period are connected with the same level of realization -- the oral portions of the brain stem. PMID- 4024792 TI - [Craniography in brain tumors]. AB - X-ray examination of 57 patients with tumours of the brain and meninges revealed general and local roentgenological alterations of the skull bones as well as secondary changes in the sella turcica. Tumours of the brain and meninges were associated with a diminution or an enlargement of the volume of the skull bones, intensification of the vascular pattern of the cranial vault and tumour calcification. A thorough craniographic examination of patients with a suspicion of brain and meningeal tumours gives definite information about general and local alterations of the skull bones and contributes to their purposeful radiographic contrast examination, which is important when surgery is contemplated. PMID- 4024793 TI - [Experimental-psychological study in the late period of closed wartime craniocerebral injuries]. AB - An experimental psychological study covered 70 patients with a long-term progressive course of a closed craniocerebral injury (CCCI) sustained during the war. The traumatological symptomatology was characterized by unstable working capacity, exhaustibility, deteriorated memory, inconsistent thinking, low self esteem and a lower level of aspirations, weakening of incentives, the presence of residual disorders of speech and visual-spatial orientation. Patients with a predominant cerebrovascular disease, along with exhaustibility characteristic of traumatic pathology, showed general inhibition, inertia, rigid processes, memory deterioration, as well as poor ability for generalization and abstract thinking, lack of interests and uncritical perception of information. The results obtained should be considered in the differential diagnosis of the clinical variant of the progressive time-course at a long-term period of a CCCI as well as in the assessment of the patient's working ability and the causes of disability. PMID- 4024794 TI - [Clinico-dynamic features of neurotic and psychotic hysterical depressions in the late period of craniocerebral injuries]. AB - Twenty patients with neurotic and twenty patients with psychotic hysterical depressions developing in the presence of long-term consequences of craniocerebral injuries were subjected to a comparative examination. Differences and transitions between these two conditions are not a uniform intensification of a definite set of symptoms but present a qualitative transformation of the status with extension of disorders to all spheres of mental activity. PMID- 4024795 TI - [Recovery of consciousness after prolonged coma in patients with severe craniocerebral injuries]. AB - The authors specify and describe 7 stages of regaining consciousness by patients who had been in coma from 11 to 180 days, including opening of the eyes; fixation of the eyes on an object; recognition of close relatives; understanding of directly addressed speech; patient's own speech; amnestic confusion; consciousness with all formal signs of being clear. The condition of the patients at these stages is compared with EEG findings suggestive of the functional disintegration of the brain as a system in comatose patients, the vegetative status and the restoration of connections between different departments of the brain corresponding to the recovery of long absent consciousness of patients. It is concluded that at the current stage of medical sciences the maximum duration of coma compatible with the subsequent full recovery of mental activity of the patient under 30 years does not exceed 11 days. PMID- 4024796 TI - [Population patterns in the dynamics of episodes and remission in patients with endogenous psychoses]. AB - Analyzing the data on 1770 patients with paroxysmal schizophrenia with a disease standing of 15 years and over, the authors established a statistically significant correlation between the clinical picture of remissions and attacks in the preceeding and the subsequent cycle of the disease. This correlation was expressed in the fact and from the second cycle to the third, the probability of the appearance of the same psychopathological disturbances was at least two times as that of the development of any other concrete disorders. The first three cycles of the disease were analyzed. PMID- 4024797 TI - [Family background of patients with slowly progressive childhood schizophrenia with a syndrome of pathologic fantasizing]. AB - The authors studied the familial background of 50 probands suffering from slowly progressive infantile schizophrenia with the morbid fantasy making syndrome. A total of 110 firstkin relatives (100 parents and 10 siblings) were examined. The incidence of manifest psychoses in parents was 16% (8 persons) in the first group of probands and 6% (3 persons) in the second group. "Subclinical forms of psychosis" and personality abnormalities of the type of sthenic schizoids were also prevalent among the relatives of the second group probands (22% and 28%, respectively). Parents denoted as schizoids with a marked emotional defect were present only in the families of the Group I probands (10%) while individuals of a hyperthymic type were observed only in the families of Group 2 probands (16%). Parents considered as normal were markedly prevalent among the relatives of Group I probands (16% and 6%, respectively). PMID- 4024798 TI - [Clinico-epidemiologic characteristics of a contingent of chronic schizophrenic patients of the "new type"]. AB - Using clinico-epidemiological research methods, the authors have studied 260 schizophrenic patients in whom the disease was first manifested in the period when wide-scale combined rehabilitation programmes were under way. It has been demonstrated that the incidence of chronic schizophrenia shows no tendency to decrease despite the use of modern rehabilitation methods. Chronicity itself has become more variable in its manifestations; thus the population of "chronics" is mostly made up of young people. An analysis of the time-course of invalidization of schizophrenic patients in the first four years of the disease has indicated a clear-cut peak at the second year after the manifestation of the process. The findings obtained made it possible to describe a number of parameters of functioning of "chronic patients of a new type". It has been shown that these patients are young and characterized by a comparatively short duration of the disease, frequent rehospitalization, marked manifestations of social disadaptation in the presence of externally normal behaviour due to rapid incapsulation of the current symptomatology, formally intact familial ties and a high frequency of abnormal behavioural manifestations. PMID- 4024799 TI - [Neuropsychiatric disorders in adolescent disorders of menstrual function]. AB - The clinical time-course of the psychic status was examined in 98 girls aged 11 to 16 years who suffered from juvenile hemorrhagas. The author identified the asthenovegatative (n-30), anxiety (n-29), anxiety-hypochondriac (n-19), obsessive fobic (n-20) and depressive-hypochondrias (n-21) syndromes. These states reflected a relatively superficial (neurotic) level of neuropsychic disorders in the patients. PMID- 4024800 TI - [Interpersonal relations in groups of mentally ill and mentally healthy children]. AB - Using the sociometric method supplemented by systematic observations, the authors studied the interpersonal relations in children's departments of mental and therapeutic hospitals. The subjective structures of choices were compared with the objectively forming interrelations. Mental patients showed a greater rigidity of these structures which remained unaltered even with the arrival of newcomers, which is explained by a relatively minor role played by such a factor as socialization. The nosological characteristics influenced the sociometric choices only indirectly, with the main structural factors being sex and age. The position of each patient in this structure was altered in parallel with the change in his or her mental status. Unlike the therapeutic department, characteristic of mentally ill patients was the limitation of choices by sex; they also differed by the fact that girls had two types of leaders. PMID- 4024801 TI - [Role of the clinical polymorphism of epileptic psychoses in determining the prognosis for patient disability]. AB - The clinical findings obtained during an examination of 98 epileptic patients make it possible to outline some criteria of occupational prognosis in diseases running with transitory, paroxysmal and chronic psychoses of the complicated structure. The variability of the outcomes of these psychoses is explained by the differences in their psychopathological structure and duration as well as in the degree of the productive symptomatology at different stages of the epileptic process. PMID- 4024802 TI - [Prognosis of epilepsy in light of catamnestic studies]. AB - As a result of a long-term follow-up of 300 epiletic patients the author has determined clinical and social factors of the favourable and unfavourable prognosis in epilepsy. The prognosis is determined by the severity of the organic brain lesion underlying epilepsy, the localization and activity of the epileptic focus, its time-course, the tempo of the increase of psychopathological and paroxysmal disorders, the effect of intercurrent diseases, psychotraumatic situations, as well as by the early and adequate therapeutic and rehabilitation measures. Of a significant role in such prediction is the assessment of the clinical manifestations of the disease during its progression under conditions of drug therapy, as well as a number of social fastors (the capacity to work and learn, marital status, etc.). PMID- 4024803 TI - [Ultrastructure of epileptic foci in temporal epilepsy]. AB - An electron microscopy study was conducted on the material of biopsies from the removed epileptic foci localized in the hippocamp and fields 21 and 38 of the temporal cortex of 11 patients with temporal epilepsy. There was the constant presence of so-called dark and altered light neurocytes whose cytoplasm had experienced considerable changes and was saturated with various inclusions. The axons and dendrites of the cells underwent peculiar degeneration. The authors revealed multiple agglutination of synaptic vesicles in the preterminals and synaptic buds, and also dark degeneration of the axonal endings in the absence of Waller's degeneration of axons. Marked changes in the walls of the capillaries were also found. PMID- 4024804 TI - [Features of the EEG correlates of activity in epileptic patients]. AB - A correlational analysis of the EEG in epileptic patients and normal subjects made it possible to elucidate differences in the brain activity in the performance of similar tasks: the performance of the correction test, collection of the Link cube, exercise with a hand expander. It is supposed that in disease, the performance of a motor act is achieved through some functional elements of the brain, which are different from normal. PMID- 4024805 TI - [Mechanisms of development and blockade of epileptic activity in the brain]. AB - Experiments on mollusk neurons showed the presence of 3 types of neurons with different activity character and different sensitivity to convulsants. The highest sensitivity to corazol and other convulsants was characteristic of spontaneuosly active "impulse" motoneurons with the threshold dose of corazol being 1 X 10(-4) M. Intergrative neurons without background spontaneous activity were the least sensitive, with the threshold dose of corazol being 1-5 X 10(-3) M. "Impulse" cells of the mollusk were compared with epileptic neurons of the brain. It was shown that "impulse" and epileptic activity was brought about by a peculiar change in the ionic permeability of the membrane, activation of the channels of a slow ascending current, a slow growth of potassium permeability and the resultant appearance of an area of negative resistance in the volt-ampere characteristics of ionic currents of the membrane. The convulsants were capable of inducing these changes in the electrophysiological characteristics of the neuronal membrane, while classical anticonvulsants eliminated them. PMID- 4024806 TI - [Immunoenzyme analysis of the antigenic orientation of "anti-brain" autoantibodies in the serum of epileptics]. AB - With the help of a solid-phase ELISA and the test system of rat brain antigens (protein fractions divided by isoelectrofocusing into zones differing in pI values) the authors discovered autoantibodies to species-nonspecific protein antigens of the brain in the blood sera of epileptic patients and obtained data on the spectra of the antigenic orientation of these autoantibodies. It has been noted that the epileptics' blood sera are characterized by high titres of autoantibodies to glial brain-specific proteins of the group S-100, as well as by undifferentiated proteins, with pI values 3-3.5 and 5-5.5. There were no significant differences in the spectra of the antigenic orientation of autoantibodies in patients with different frequencies of seizures and the localization of the epileptic focus. Considerable differences in the orientation of cerebral autoantibodies in patients with different disease standing were discovered. PMID- 4024807 TI - [Features of changes in the EEG of patients with repeated syncope and epileptic seizures between attacks]. AB - On the basis of a comparative computerized analysis of EEG findings obtained from 81 patients with repeated syncopes and 56 with epileptic attacks the authors derived statistically significant data about the differential-diagnostic value of 11 electroencephalographic signs which allowed the differentiation of these groups of patients. PMID- 4024808 TI - [Activity of polymorphic N-acetyltransferase in epilepsy]. AB - Activity of polymorphic N-acetyl transferase characterized by bimodality (fast and slow acetylators) in normal subjects was studied in 150 epileptic patients. The epileptic versus normal subjects had a significant predominance of slow acetylators. The data obtained suggest that slow acetylation is one of the possible factors predisposing to epilepsy and responsible for a more severe course of the disease. The results of the study suggest that determination of the activity of polymorphic N-acetyl transferase may serve as a prognostic criterion of epilepsy. PMID- 4024809 TI - [Dermatoglyphic traits in the diagnosis and prognosis of epilepsy]. AB - A total of 549 epileptic children and 162 healthy children were studied dermatoglyphically. The authors found significant dermatoglyphic differences between the control subjects and patients suffering from epilepsy with a progressive and an unprogressive course. Dermatoglyphic characteristics in the epileptic patients varied in groups with different clinical characteristics (age at the onset of the disease and the duration of the latter, the daily development of paroxysms at the same time, a tendency toward a stable course, the presence of psychic states and the resistance to therapy). Statistical task-solving rules for diagnosing epilepsy in children were elaborated. The correct computer-aided diagnosis on the basis of dermatoglyphic examination was made in 70% of the epileptic patients. PMID- 4024810 TI - [Paroxysmal disorders during sleep as the debut of epilepsy in children]. AB - The authors examined 100 children aged 3 to 14 years with paroxysmal disturbances during sleep, which were the first manifestations of epilepsy. On the basis of a long-term follow up these disturbances were differentiated clinically from similar disorders of non-epileptic nature. The most typical epileptic disturbances occurring during sleep (psychomotor paroxysms, crying, laughter, night fears, nightmarish dreams, psychosensory disorders) had some characteristics in common, namely changes in consciousness, appearance almost at the same time, stereotyry of the manifestations, attendant autonomic disorders, nocturnal enuresis followed by the development of the typical epileptic forms of attacks. The treatment of paroxysmal disturbances was conducted with regard to their clinical structure and the localization of the epileptic focus. PMID- 4024811 TI - [Neuropsychiatric disorders in children whose relatives have epilepsy]. AB - Using clinical electro-encephalic and experimental psychological methods, 75 children born to epileptic parents were examined. The clinical picture of epilepsy in children was found to correlate with the severity and duration of the disease in the parents. In the majority of children the onset of the disease was characterized by non-convulsive paroxysms. The main course of disadaptation of the children to the environment, which hindered their learning in school was mental change expressed in the form of intellectual, emotional and characterological disorders. PMID- 4024812 TI - [Course of epilepsy in patients who have suffered adverse effects of anticonvulsant preparations according to the results of long-term follow-up]. AB - The author studied 99 epileptic patients in whom 5-10 years ago anticonvulsants had caused side-effects. In 10% of the patients, a stable remission of the paroxysmal manifestations and an improvement of the mental status was achieved after controlling the complications. The majority of the patients exhibited slow progression of the epileptic process following a reduction of disturbances induced by intoxication and folic acid deficiency. Severe toxic, metabolic and allergic complications (30%) were followed by further considerable progression of the paroxysmal and psychopathological symptomatology. The degree of progression and severity of the organic brain lesion in epileptic patients is an important factor affecting the manifestation of the side-effects associated with anticonvulsants and the efficiency of further anticonvulsive therapy. In 4% of the patients the author observed repeated drug-induced complications. The prophylaxis of repeated complications of the anticonvulsant treatment prevents epilepsy aggravation. PMID- 4024813 TI - [Tactics for managing patients who developed epileptic seizures and paroxysmal states for the first time]. AB - The authors examined 230 patients who developed paroxysmal conditions. The majority of patients (n-193) presented with epileptic seizures. In the remaining 37 patients various syncopal conditions were diagnosed. The authors emphasize the necessity of a comprehensive examination of such patients, the early detection and treatment of somatic pathology which usually aggravates the course of epileptic process at the early stages. The authors advocate an active multimodality treatment of patients who developed seizures for the first time, the therapeutic and diagnostic use of pneumoencephalography with the administration of nitrous oxide into the cerebrospinal fluid. Approximate schemes of the treatment of patients are offered and a long-term follow-up on the outpatient basis is recommended. PMID- 4024814 TI - [Cerebral contusions in injuries with fractures of the bones of the skull in children]. AB - The authors analyzed 205 cases of skull fractures in children. Linear, depressed and comminuted skull fractures as well as ruptures of the cranial commissures were revealed. Skull fractures in children were characterized by specific features depending on the age, type of fractures and the mechanism of injury and were always attended with contusions of the brain. To determine the degree of brain contusions, the authors carried out a comprehensive examination with the use of electrophysiological and modern laboratory methods (determination of blood plasma prostaglandins). PMID- 4024815 TI - [Relation between the sequelae of craniocerebral injuries and the site of cerebral contusion]. AB - The study of the consequences of the craniocerebral trauma in 58 patients with brain contusion of moderate severity has shown that the localization of contusion foci largely determines the nature and degree of posttraumatic changes. PMID- 4024816 TI - [Polygraphic features of the structure of nocturnal sleep in pathology of the left and right hemisphere in stroke patients]. AB - The results of polygraphic examination of night sleep in 40 post-stroke patients are presented. In 22 of these patients, the focus was localized in the left, and in 18, in the right hemisphere. The pattern of sleep was found to vary with the hemispherical lateralization of the pathological process. Patients with damage to the left hemisphere and aphasia exhibited differences in the phase of rapid sleep and the time-course of the activation phenomena on the EEG during sleep related to the degree of speech disturbances. When the right hemisphere was impared, the most marked disturbances of the sleep pattern were elicited in patients with prominent manifestations of anosognosia. The data obtained are considered as features characteristic of the dysfunction of the cerebral nonspecific systems associated with hemispherical damage. PMID- 4024818 TI - [Professorial patient rounds in a nervous diseases clinic]. PMID- 4024819 TI - Thermal injuries of human tendons. AB - Forty-two burn injuries and 22 cold injuries were investigated. Both high temperature and cold induced tenocyte necrosis, and denatured and fragmented the collagen fibres. As a consequence of severe damages of tendon and of long lasting regeneration, it was believed that even in case of incidental healing restoration of the original function could not be expected. PMID- 4024817 TI - [Thermography in healthy subjects and in the syndrome of vegetative-vascular dystonia]. AB - The effectiveness and information content of thermography were studied in 20 normal subjects and 40 patients with vegetative vascular dystonia. There were some individuals in the control group who had "thermal amputation" and who also had some specific features of psychovegetative nature. Patients with vegetative vascular dystonia, apart from the syndrome of "thermoamputation" observed in a great number of cases, particularly in neurotic patients, had other types of skin temperature distribution as well. Thus, patients with hypothalamic insufficiency presented with hyperthermia of the distal portions of the extremities and asymmetry. PMID- 4024820 TI - Arthroplasty combined with cup-plastics in the surgical treatment of congenital dislocation of the hip. AB - The authors review the arthroplasty combined with cup-plastics in the treatment of congenital dislocation of the hip. The indications and surgical exploration are discussed in detail. Good results are reported. The complications and their solutions are also described. In the recent five years, 100 patients were operated by them. Based on their experiences, they suggest this intervention at an earlier age, too (i.e. 30 to 40 years). Moreover, they believe it to be an important possibility to provide an adequate rehabilitation for patients being still of working age. PMID- 4024821 TI - Anorectal sarcomas. AB - The authors report on their observations of nine patients with anorectal sarcoma. They agree with others that best results can be expected from radical surgery. Even in operable patients anorectal sarcomas have a worse prognosis than other malignant lesions in the same region. PMID- 4024822 TI - Lung cancer: long-term survival after surgical treatment. AB - The authors have carried out an analysis on a series of 1802 patients with lung cancer. 1254 patients were considered operable (69.5%) and 828 were resected. Overall 5-year survival rate was 28.3%. Results of surgical treatment were analysed in relation to the specific features both of primary tumour and the host organism. Although patients affected with epidermoid carcinoma showed a better survival as compared to those affected with tumours of other histotypes. Conversely long-term results were significantly related to post-surgical stage. Patients treated for stage I tumour showed a significantly better long-term survival (5-year survival rate 48.2%) as compared to those undergone resection for stage II and III neoplasms (22.8% and 12%, respectively; p: less than 0.001). From the prognostic standpoint female patients undergone resection showed markedly lower long-term survival (5-year survival rate 12.5%) as compared to male patients (5-year survival rate 29.5%), but the numerical differences between the two groups of patients does not permit to detect statistically significant differences (P: less than 0.05). Type and intensity of the immune response affect significantly long-term survival. PMID- 4024823 TI - [Congenital defects of the motor system]. PMID- 4024824 TI - [Personal experience in the treatment of osteomyelitis and infected fractures]. PMID- 4024825 TI - [Principles in the use of silicone implants in finger joints using Swanson's technic]. PMID- 4024826 TI - [New approaches to the classification and treatment of open fractures]. PMID- 4024827 TI - [Surgical treatment of spinal deformities in very young individuals]. PMID- 4024828 TI - [Reconstruction of part of the knee joint]. PMID- 4024829 TI - [Articular synovial osteochondromatosis]. PMID- 4024830 TI - [Pes planus in children (theoretical part)]. PMID- 4024831 TI - [The osteocartilaginous junction in large joints]. PMID- 4024832 TI - [Comprehensive therapy of soft tissue sarcoma]. PMID- 4024833 TI - [Subluxation and pseudoluxation of the cervical spine in children]. PMID- 4024834 TI - [Replacement of the necrotic semilunar bone in Kienbock's disease using the tendon of the long palmar muscle]. PMID- 4024835 TI - [Decompensated cirrhosis and jugular turgescence. Hemodynamic study of a case of cirrhosis associated with a cardiomyopathy]. PMID- 4024836 TI - Transient heart block. An unreported toxicity of high dose chemotherapy with cyclophosphamide and etoposide. PMID- 4024837 TI - Ampicillin induced acute interstitial nephritis and Lyell's syndrome. PMID- 4024838 TI - [How to manage urinary lithiasis]. PMID- 4024839 TI - [How should we proceed when a thyroid nodule is palpated?]. PMID- 4024840 TI - [Cardiovascular pathology in sleep apnea syndrome. Apropos of a case of severe pulmonary arterial hypertension]. PMID- 4024841 TI - Campylobacter bacteraemia. Report of 2 cases and review of the literature. PMID- 4024842 TI - [Exercise-induced left-branch block without cardiac pathology]. PMID- 4024843 TI - [Evaluation of the incidence of heterozygote thalassemias in immigrants of Mediterranean origin living in the Brussels region. Definition of a strategy for detection]. PMID- 4024844 TI - [Pneumococcal peritonitis]. PMID- 4024845 TI - How should we proceed when a hyponatremia is discovered? PMID- 4024846 TI - Drugs recently released in Belgium. Ceftriaxone. PMID- 4024847 TI - Systemic sclerosis, aplastic anemia and amyloidosis associated with lung carcinoma. PMID- 4024848 TI - DNA and S-phase representation in human growth hormone producing pituitary adenomas. AB - The DNA contents of 33 pituitary adenomas from patients with acromegaly were analysed with flow-cytofluorometry. Degrees of ploidy and the proliferation rate, expressed as percentage of cells in S-phase, were determined. The aim was to compare these morphological and functional tumour properties with clinical and laboratory parameters to establish a possible relation and to further elucidate the characteristics of these tumours. In 15 tumours (45%) diploid DNA pattern were found, while 18 (55%) showed varying degrees of aneuploidy. The frequency of cells in S-phase showed wide variations and were equally distributed in diploid and aneuploid tumours. Duration of symptoms, age at diagnosis, preoperative growth hormone (GH)- and prolactin (Prl)-levels, tumour size and grade of invasive tumour growth as determined by radiological estimations, did not correlate to ploidy or grade of proliferation. The lack of correlation between DNA pattern and proliferation rate in relation to clinical, laboratory and radiological parameters in tumours causing acromegaly contrasts to the documented relation between the degree of ploidy, cells in proliferation and grade of malignancy reported in tumours of other sites. The 55% aneuploid GH producing tumours indicate a certain malignant transformation. The high frequency of cells in S-phase in several GH secreting tumours completes the malignant morphological and functional cell properties. The benign character of tumours causing acromegaly is therefore in contrast to these findings. The lack of clinical significance of the DNA pattern and the frequency of cells in proliferation in GH producing tumours and the benign character despite malignant cell properties in most of these tumours are difficult to explain.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4024849 TI - Persistence of a defective tuberoinfundibular dopaminergic function in rats after long-term removal of oestrogen treatment. An in vivo study. AB - The function of the tuberoinfundibular dopaminergic (TIDA) neurons of 49 rats bearing oestradiol-valerate (EV)-induced prolactin (Prl) secreting tumours (prolactinomas) was evaluated in vivo, 7 months after discontinuation of EV treatment, with neuroactive drugs acting via stimulation or inhibition of DA neurotransmission. Based on the size and morphologic appearance of the pituitary and on determination of plasma Prl levels, rats previously treated with EV could be divided into those bearing macro- (31/49) and those bearing micro prolactinomas (18/49). Administration of the indirect DA agonist drug nomifensine (10 mg/kg iv) lowered plasma Prl levels in control rats, but failed to do so in rats bearing either macro- or microprolactinomas. Administration of the DA receptor antagonist domperidone (50 micrograms/kg ip) or the synthetic enkephalin analogue FK 33-824 (1 mg/kg ip) failed to induce a rise in plasma Prl in rats with macro-, but induced a clear-cut rise in plasma Prl in those with microprolactinomas. Prl unresponsiveness to all three neuroactive drugs indicates that long time after EV withdrawal TIDA neuronal function is still highly impaired in rats bearing EV-induced macroprolactinomas. The impairment of TIDA neuronal function would be of lesser extent in rats bearing microprolactinomas as revealed by a defective response to only one of the three applied neuroendocrine probes. PMID- 4024850 TI - Early effect of thyroid hormone on cytosolic protein phosphorylation in rat anterior pituitary. AB - The effect of T3 was studied on phosphorylation of cytosolic proteins in rat anterior pituitary. Cytosols obtained from hypothyroid (H) and T3 (50 micrograms/100 g body weight) injected H rats (T) were phosphorylated in vitro. Although total incorporation of 32P into proteins did not differ between H and T, analysis of phosphoproteins by SDS polyacrylamide gel electrophoresis and autoradiography revealed that T3 injection significantly increased phosphorylation of 2 proteins within 1 h. These results and our previous demonstration of T3 effects on phosphorylation in rat liver cytosol and cultured human skin fibroblasts suggest that protein phosphorylation is an important early intracellular process in T3 action. PMID- 4024851 TI - The vasopressin response to microinjections of norepinephrine into the brain of the conscious pig. AB - The possibility that the amygdala influences the release of vasopressin has been raised by the observation that electrical stimulation of this area results in vasopressin release in the conscious animal. Therefore the effect on vasopressin concentrations has been studied by microinjections of norepinephrine into the amygdala of the conscious miniature pig. The studies were performed on castrated male and female pigs with chronically implanted cannulae in the brain and in the external jugular vein. Lysine vasopressin concentrations were determined using a specific sensitive radioimmunoassay. Microinjections of 1 microliter 0.12 M sodium chloride were without effect. Injections of norepinephrine in the dose range 10(-4)-10(-10) M had no effect in the male animal but a significant vasopressin response could be obtained in the females. PMID- 4024852 TI - Inhibition of phytohaemagglutinin-induced lymphocyte blastogenesis by serum from pregnant women: correlation between cortisol level and in vitro immunosuppression. AB - Peripheral human blood lymphocytes stimulated by optimal doses of phytohaemagglutinin (PHA) were cultured in the presence of serum obtained from non-pregnant (controls) and pregnant women at different stages of gestation. A significant inhibitory influence on cellular growth was identified in the serum from pregnant women from the second trimester onward but more pronounced at the end of gestation. This inhibition was strongly correlated with the levels of cortisol in the sera. The action of commercial cortisol on lymphocyte reactivity in cultures stimulated by various concentrations of PHA and containing either a pool of pregnancy sera, or a pool of non-pregnancy sera, or a mixture of these pools was also investigated. The hormone provoked a significant inhibition more evident when low doses of PHA were used. The same finding occurred with the gravida's sera pool supplemented cultures. PMID- 4024853 TI - Catechol oestrogen induced initiation of implantation in the delayed implanting rat. AB - In the rat oestrogen is essential for induction of implantation in a progesterone primed uterus. The ability of the catechol oestrogens, 4-hydroxy-oestradiol (4-OH E2) and 2-hydroxy-oestradiol (2-OH-E2) to initiate the implantation process (blue reaction, indicative of increased endometrial capillary permeability at the location of the blastocyst) in hypophysectomized delayed implanting rats was compared to that of oestradiol-17 beta (E2). Delayed implantation was maintained by daily administration of 2 mg of progesterone. A single sc injection of 100 ng of E2 or 400 ng of 4-OH-E2 consistently initiated implantation in all animals. When delivered sc via osmotic minipumps at a constant release rate of 10 ng/microliters/h, implantation of a full complement of embryos was obtained with E2 given for 6 or 24 h. This dose 4-OH-E2 was ineffective when administered for 24 h. However, 25 ng/microliters/h for 24 h was effective. When the dose was increased to 50 ng/microliters/h implantation was evident in the majority of animals exposed to the hormone for 6 or 8 h; all animals implanted when this dose was given for 24 h. In contrast, 2-OH-E2 given at 50 ng/microliters/h for 24 h was totally ineffective. When the dose of the latter steroid was raised to 200 ng/microliters/h implantation was achieved in half of the animals when exposure was 24 h. The results suggest that when administered systemically, 4-OH-E2 is less potent than E2, but more potent than 2-OH-E2, for initiating implantation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4024854 TI - A retrospective analysis 21 to 35 years after birth of hydrocephalic patients born from 1946 to 1955. An overall description of the material and the criteria used. AB - 219 patients diagnosed as having hydrocephalus before the age of 5 years were traced 21 to 35 years after birth. Fifty-four patients had had operations, but those used before the introduction of ventriculo-atrial shunts did not influence the outcome; the series may be considered to represent the natural history of hydrocephalus. Based on available information in the case notes, patients were divided into 2 groups: 1) proven hydrocephalus, and 2) unproven hydrocephalus. Strict criteria were used. Ninety-nine patients (45%) had died. Serious prognostic factors as to survival were early admission, increasing head circumference, downward displacement of the eyes, and seizures. Together with the criteria suggested for proven hydrocephalus, the above factors may act as a guideline to operative treatment. Fifty-seven percent of 116 known survivors were able to work, 9% lived independently but had no working ability, and 34% needed permanent care or supervision. This outcome is similar to that of shunt-operated patients followed for a shorter period. The only parameters indicative of socio economic independence in adult life were early admission and absence of seizures in childhood. PMID- 4024855 TI - An improvement in cognitive function following polypharmacy reduction in a group of epileptic patients. AB - 18 epileptic patients on polypharmacy were assessed, using a battery of psychometric tests including the Wechsler Adult Intelligence Scale, Benton Visual Retention Test and Alertness and Concentration tests. The same patients were reassessed one year later following a trial to reduce their polypharmacy. The results for 12 patients whose treatment was reduced to monotherapy were statistically analysed, using the Wilcoxon Matched Pairs Test. Significant changes were found on a number of test scores which included Full Scale WAIS I.Q., W.A.I.S. Performance I.Q., Digit Symbol, Block Design and Object Assembly, Benton Visual Retention Test Error Score and Concentration Test Score. The other tests showed no improvement over baseline. The results point to the improvement in some areas of cognitive function which follows a reduction in polypharmacy to monotherapy. PMID- 4024856 TI - Regional cerebral blood flow and CSF pressures during Cushing response induced by a supratentorial expanding mass. AB - In order to delineate the critical blood flow pattern during the Cushing response in intracranial hypertension, regional cerebral blood flow was measured with radioactive microspheres in 12 anesthetized dogs at respiratory arrest caused either by expansion of an epidural supratentorial balloon or by cisternal infusion. Regional cerebrospinal fluid pressures were recorded and the local cerebral perfusion pressure calculated in various cerebrospinal compartments. In the 8 dogs of the balloon expansion group, the systemic arterial pressure was unmanipulated in 4, while it was kept at a constant low level (48 and 70 mm Hg) in 2 dogs and, in another 2 dogs, at a constant high level (150 and 160 mm Hg) induced by infusion of Aramine. At respiratory arrest, regional cerebral blood flow had a stereotyped pattern and was largely independent of the blood pressure level. In contrast, concomitant pressure gradients between the various cerebrospinal compartments varied markedly in the 3 animal groups, increasing with higher arterial pressure. Flow decreased by 85-100% supratentorially and by 70-100% in the upper brain stem down to the level of the upper pons, while changes in the lower brain stem were minor, on the average 25%. When intracranial pressure was raised by cisternal infusion in 4 dogs, the supratentorial blood flow pattern at respiratory arrest was approximately similar to the flow pattern in the balloon inflation group. However, blood flow decreased markedly (74-85%) also in the lower brain stem. The results constitute another argument in favour of the Cushing response in supratentorial expansion being caused by ischemia in the brain stem. The critical ischemic region seems to be located rostrally to the oblongate medulla, probably in the pons. PMID- 4024857 TI - Anticoagulant-induced intracerebral bleeding in brain ischemia. Evaluation in 200 patients with TIAs, emboli from the heart, and progressing stroke. AB - During a 5-year period, 85 patients with TIAs, 65 patients with embolic brain ischemia of cardiac source and 50 patients with progressing stroke received intravenous heparin within 96 h. Twelve (6%) developed an early bleeding in the area involved by ischemia. In the 2 cases with transient ischemic attacks (TIAs) (2.3%), major functional sequelae persisted and the 2 cases with emboli from heart (3.2%) died, whereas among the 8 cases with progressing stroke (16%), only 3 worsened from anticoagulant-induced bleeding. Intracerebral bleeding was not associated with excessive anticoagulation or high blood pressure and was related to a large infarction only in the cases with emboli from the heart. Among the 108 patients who were placed on acenocoumarol during 3-12 months after heparin therapy, only one (0.9%) suffered a hemorrhagic infarct from a probable recurrent embolization. The risk of anticoagulant-induced intracerebral bleeding is quite different between the varieties of preceding ischemic events, with different subsequent impact on prognosis. PMID- 4024858 TI - The natural history and the influence of surgical treatment in syringomyelia. AB - A retrospective analysis was made of the natural history and treatment of 44 patients with syringomyelia, followed for a median interval of 10 years after diagnosis. Twenty-four patients were treated surgically. Four of 12 patients who had a laminectomy with aspiration of the syrinx or syringostomy, and 7 of 15 patients who underwent decompression and exploration of the cervicomedullary junction, showed sustained improvement or stabilisation of their neurological deficits. When symptoms had been present for more than 2 years, when there was a moderate or severe neurological disability, and when the patient was more than 40 years old, the long-term outlook of posterior fossa surgery was usually poor. Of the 20 patients who did not have an operation, 7 had no further progression in symptoms after presentation and prolonged survival was usual. It is concluded that in many cases syringomyelia is compatible with prolonged survival, and although improvement can follow surgery, its influence on the disease in the long term is uncertain. PMID- 4024859 TI - Cognitive impairment in motor neuron disease. AB - A systematic investigation of the cognitive functions of 22 patients affected with motor neuron disease (MND) compared to 36 controls matched for age and education was performed. The MND group showed cognitive performances slightly but significantly lower than the control group; 6 MND patients, however, had decidedly pathological values. Cognitive impairment was stereotyped and global, with sparing of memory. There was no significant difference between patients with isolated involvement of the lower motor neuron and those with associated pyramidal involvement. Our neuropsychological findings are in agreement with previous clinical, neuroradiological and pathological reports indicating extra motor cerebral involvement in MND. PMID- 4024860 TI - Enteric-coated acetylsalicylic acid plus dipyridamole compared with anticoagulants in the prevention of ischemic events in patients with transient ischemic attacks. AB - From December 1976 through March 1982, 188 patients entered an open non-random study carried out on hospitalized patients with a history of transient ischemic attacks or amaurosis fugax. Ninety-two patients received peroral anticoagulants usually combined with heparin treatment during the first days of treatment, and 96 patients enteric-coated acetylsalicylic acid 0,5 g twice daily plus dipyridamole 75 mg twice daily. The patients were followed up to March 1983, irrespective of whether treatment was changed or not. Recurrent transient ischemic attack or amaurosis fugax occurred more frequently (P less than 0.01) from 2 months of follow-up and throughout the observation period in the antiplatelet-treated group. There were no statistically significant differences between the 2 groups on the originally given treatment for endpoints such as stroke (6 patients on anticoagulants, 12 patients on antiplatelet therapy) or stroke or death (11 patients on anticoagulants, 17 patients on antiplatelet therapy). The findings from this trial suggest that anticoagulant treatment is superior to antiplatelet therapy given in the prevention of ischemic attacks and that this difference mainly exists during the first one to 2 months after onset of transient ischemic attacks or amaurosis fugax. PMID- 4024861 TI - Intrathecal synthesis of different alpha-interferons in patients with various neurological diseases. AB - CSF and sera from 238 newborns and children with various neurological diseases were assayed on bovine cells for the presence of alpha-interferon (IFN). An intrathecal synthesis of pH 2-resistant alpha-IFN was recovered in all newborns and in more than 90% of children with herpes encephalitis. It was also observed in one case of mumps encephalitis and in one case of encephalitis associated with Influenza A infection. An acid-labile alpha-IFN production was detected in CSF from more than one half of patients with viral meningitis or active congenital rubella and in those with neurological complications of systemic lupus erythematosus. This alpha-IFN subtype was also detected in CSF from only 2/37 children with measles encephalitis. In contrast, no alpha-IFN (less than 2 IU) in CSF was found among patients with subacute sclerosing panencephalitis, Guillain Barre syndrome, Reye's syndrome, acute cerebellar ataxia, infantile spasms or facial paralysis of unknown origin. PMID- 4024862 TI - Ferritin concentration in cerebrospinal fluid. AB - 15 patients with psychosomatic disease, 26 patients with miscellaneous neurological diseases, and 16 patients with cerebrovascular disease were investigated with regard to concentrations of ferritin in serum and cerebrospinal fluid (CSF). The mean CSF ferritin concentration in the psychosomatic group was 6.2 micrograms/l +/- 2.4 (1 S.D.). Patients with recent cerebral infarction had similar values while 2 patients with intracerebral hematomas had very high CSF ferritin concentrations. There was a positive correlation between serum and CSF ferritin levels and between CSF total protein and ferritin in patients with a damaged blood-CSF barrier only. At present, the practical value of analysing ferritin in the CSF is very small. PMID- 4024863 TI - Glial fibrillary acidic protein in medulloblastomas. AB - Two cases of medulloblastoma are described which show positive immunostaining for glial fibrillary acidic protein (GFAP) in many cells. The surgical and autopsy specimens were examined by the indirect immunoperoxidase method. Positive staining for GFAP was demonstrated in the small, round to polygonal cells in both surgical specimens and in the small spindle cells in the autopsy specimen of one case. In the small, round to polygonal cells positive GFAP was shown as a perinuclear brown rim or intracytoplasmic brown droplet. In the small spindle cells, the cytoplasm and the polar processes were stained. Except for GFAP staining, these positive cells were morphologically indistinguishable from the accompanying unstained cells, indicating that GFAP was expressed in the medulloblastoma cells. Considering that GFAP is specific for astrocytes, these findings suggest the potential of astrocytic differentiation in the neoplastic cells of these medulloblastomas. The findings obtained in other 28 medulloblastomas examined in parallel are also discussed briefly. PMID- 4024864 TI - Postnatal sudanophilic leukodystrophy in two siblings. AB - Reported here are two siblings with sudanophilic leukodystrophy occurring in early infancy. Soon after birth, high fever, distension of the abdomen and spasticity of the extremities were noted. Neurologic disorders, frequent convulsive seizures, and malnutrition caused both siblings to die at the age of 3 and 6 months, respectively. Neuropathologic examination of the brain revealed diffuse demyelination in the cerebral and cerebellar white matter as well as a disturbance of the myelination, especially in the descending pathway. Numerous sudanophilic lipids and glial fibers proliferated in the demyelinated areas. Neurochemically, there was a marked decrease in all lipid components, cholesterol, phospholipids, and glycolipids and an increase in cholesterol ester. Fatty-acid composition of cerebroside and sulfatide, especially that of long chain acids, was within normal range, unlike the fatty-acid composition found in connatal Pelizaeus-Merzbacher disease. The brain damage in postnatal infant caused by frequent convulsive seizures and the severe demyelination in the cerebral and cerebellar white matter in both patients are discussed. The cases of sudanophilic leukodystrophy and Pelizaeus-Merzbacher disease occurring in children under 5 years of age are reviewed. PMID- 4024865 TI - Early changes in experimental denervated rat gastrocnemius muscle. A semi automatic quantitative study. AB - Computer-aided image analysis of EM images reveals important morphometric alterations after only 10 days of rat gastrocnemius denervation. The increasing importance of early quantitative changes in human diagnostics is stressed. PMID- 4024866 TI - The temporal evolution of hypoglycemic brain damage. I. Light- and electron microscopic findings in the rat cerebral cortex. AB - In the course of a study on the pathogenesis of neuronal necrosis in severe hypoglycemia, the morphological characteristics reflecting reversible and irreversible neuronal lesions were examined as a function of time following normalization of blood glucose. To that end, closely spaced time intervals were studied in the rat cerebral cortex before, during, and up to 1 year after standardized pure hypoglycemic insults of 30 and 60 min of cerebral isoelectricity. Both the superficial and deep layers of the cerebral cortex showed dark and light neurons during and several hours after the insult. By electron microscopy (EM) the dark neurons were characterized by marked condensation of both karyoplasm and cytoplasm, with discernible, tightly packed cytoplasmic organelles. The light neurons displayed clustering of normal organelles around the nucleus with clearing of the peripheral cytoplasm. Some cells, both dark neurons and neurons of normal electron density, contained swollen mitochondria with fractured cristae. Light neurons disappeared from the cerebral cortex by 4 h of recovery. Some dark neurons in the superficial cortex and almost all in the deep cortex evolved through transitional forms into normal neurons by 6 h recovery. Another portion of the dark neurons in the superficial cortex became acidophilic between 4 and 12 h, and by EM they demonstrated karyorrhexis with stippled electron-dense chromatin. The plasma membrane was disrupted, the cytoplasm was composed of amorphous granular debris, and the mitochondria contained flocculent densities. These definitive indices of irreversible neuronal damage were seen as early as 4-8 h recovery. Subsequently, the acidophilic neurons were removed from the tissue, and gliosis ensued. Thus, even markedly hyperchromatic "dark" neurons are compatible with survival of the cell, as are neurons with conspicuous mitochondrial swelling. Definite nerve cell death is verified as the appearance of acidophilic neurons at which stage extensive damage to mitochondria is already seen in the form of flocculent densities, and cell membranes are ruptured. Our previous results have shown that hypoglycemic neocortical damage affects the superficial laminae, chiefly layer 2. The present results demonstrate that, following the primary insult, this damage evolves relatively rapidly within the first 4-12 h. We have obtained no evidence that additional necrotic neurons are recruited after longer recovery periods. PMID- 4024867 TI - Experimental neurotoxicity of the anorectic fenfluramine. I. A fine structural model for cerebral lysosomal storage and neuroglial reaction. AB - Fenfluramine, an amphophilic compound which is a halogenated derivative of amphetamine, is still used as an anorectic agent for weight reduction, as it acts on the satiety center of the hypothalamus. Holtzman strain rats aged 6 days were daily injected s.c. fenfluramine hydrochloride at the dose of 75 mg/kg body weight. The animals were killed at different time intervals between days 7 and 40, and different parts of the brain were examined by light and electron microscopy. About half of the animals showed intralysosomal membrano-cytoplasmic bodies in the oligodendroglia, neurons, and neuropil, maximally in the animals receiving 8-19 injections. They were seen as concentrically arranged, single layered lamellae; small dense bodies; or larger heterogeneous bodies. The mechanism of production of such inclusions could be the formation of complexes of this amphophilic compound with tissue phospholipids, or some enzyme-inhibiting action. A marked prominence of dark cells, predominantly oligodendroglia, was also noticed in the brains of experimental animals. Some of these cells appeared to be dark neurons, probably resulting from the serotonin-depleting effect of fenfluramine. A few dark cells were identified as resting microglial cells, while macrophagic "reactive microglia" were detected in the brains of very young animals. Fenfluramine appears to provide a model for studying neuroglial reactions. PMID- 4024868 TI - Hirano bodies in the perikaryon of the Purkinje cell in a case of Alzheimer's disease. AB - Cylindrical forms of Hirano bodies were observed in the perikaryon of a Purkinje cell in a case of Alzheimer's disease. Scattered, typical senile plaques were also seen in the cerebellar cortex. PMID- 4024869 TI - The temporal evolution of hypoglycemic brain damage. II. Light- and electron microscopic findings in the hippocampal gyrus and subiculum of the rat. AB - Part I of this paper has documented the evolution of dark neurons into acidophilic neurons in the superficial laminae as well as the reversion of dark neurons to normal neurons in the deep laminae of the cerebral cortex in hypoglycemic brain damage. The present study describes the temporal evolution of hypoglycemic brain damage in the hippocampus. The evolution of dark neurons to acidophilic neurons was confirmed in this brain region. Four additional problems were addressed: Firstly, delayed neuronal death was looked for, and was found to occur in areas of CA1 undergoing mild damage. However, it was not preceded by a morphological free interval, had ultrastructural characteristics distinct from delayed neuronal death in ischemia, and hence should be considered a distinct phenomenon. Secondly, the gradient in the density of neuronal necrosis in the rat hippocampal pyramidal cell band was exploited to test the hypothesis that a more severe insult causes a more rapid evolution of neuronal changes. This was found to be the case, with a temporal spectrum in the timing of neuronal death: Necrosis occurred already after 2 h medially in the subiculum, and was delayed by up to several weeks laterally in CA1. Thirdly, the almost universal sparing of CA3 pyramidal neurons after 30 min hypoglycemic isoelectricity was exploited to address the question of whether reactive changes, which could with certainty be deemed reversible, occur in CA3. Mitochondrial injury was seen in these cells, and was found to be recoverable. No reactive changes of the type previously described following ischemic insults were observed. Fourthly, the astrocytic and vascular response of the tissue was studied. A sequence of astrocytic changes representing structural and probably metabolic activation of astrocytes was seen, consisting of morphological indices of increased turnover of cellular components. Capillaries demonstrated endothelial pits, vesicles, and prominent microvilli hours to days after recovery. The results demonstrate that, in the hippocampal gyrus as in other brain regions, hypoglycemic brain damage is distinct from ischemic brain damage and likely has a different pathogenesis. PMID- 4024870 TI - The temporal evolution of hypoglycemic brain damage. III. Light and electron microscopic findings in the rat caudoputamen. AB - The caudate nucleus and putamen belong to the selectively vulnerable brain regions which incur neuronal damage in clinical and experimental settings of both hypoglycemia and ischemia. We have previously documented the density and distribution of the hypoglycemic damage in rat caudoputamen, but the evolution of the injury, i.e., the sequence of structural changes, has not been assessed. Therefore, in the present study we analyze the light and electron microscopic alterations in the caudoputamen of rats exposed to standardized, pure insults of severe hypoglycemia with isoelectric EEG for 10-60 min, or in rats which, following insults of 30 or 60 min, were allowed to recover for periods from 5 min to 6 months. The hypoglycemic insult produced severe nerve cell injury in the dorsolateral caudoputamen. Immediately after the insult abnormal light neurons with clearing of the peripheral cytoplasm were present. These cells disappeared early in the recovery period, as they do in the cerebral cortex. Dark neurons were also present, but unlike those in the cerebral cortex they did not appear until recovery was instituted. Their number increased for a couple of hours and they became acidophilic within 4-6 h. At this stage, electron microscopy revealed severe clumping of the nuclear chromatin and cytoplasm as well as incipient fragmentation of cell membranes, all these changes indicating an irreversible injury. Within 24 h flocculent densities appeared in the mitochondria and by day 2-3 of recovery the great majority of the medium-sized neurons had undergone karyorrhexis and cytorrhexis, their remnants being subsequently removed by macrophages. After some weeks only large and a few medium-sized neurons remained amidst reactive astrocytes and numerous macrophages. The delay in the appearance of dark, lethally injured medium-sized neurons until the recovery was instituted suggests an effect that does not become apparent until the substrate supply and energy production are restored. Furthermore, it points out again the selectivity of the hypoglycemic nerve cell injury with respect to the type (metabolic characteristics?) and topographic location of the neurons. PMID- 4024871 TI - The distribution of laminin in human brain tumors: an immunohistochemical study. AB - The immunohistochemical distribution of laminin in 70 cases of primary and secondary brain tumors has been studied. The sections were fixed in Carnoy, embedded in paraffin, and treated with collagenase before applying the specific immune serum. In normal neural tissue and in gliomas, the distribution of laminin overlaps with that of basement membrane, as is known from observations on ultrastructure in the literature. The overlapping was observed also in neurinomas, papillomas of the choroid plexus, ependymomas, and meningiomas. Problems arise in the interpretation of the results in the other oncotypes. In hemangiopericytomas and hemangioblastomas, laminin demonstrates a basement membrane around the vessels only; it is absent around stromal cells. In desmoplastic medulloblastomas, laminin forms a network among the tumor cells. In primary lymphomas, concentric rings of laminin are evidenced around some vessels. In discussing the results, the ultrastructural distribution of basement membranes is taken into account. PMID- 4024872 TI - Damage of Purkinje cell axons following chronic phenytoin administration: an animal model of distal axonopathy. AB - An animal model of central distal axonopathy following chronic administration of phenytoin is described. Male C57/BL6J mice received diphenylhydantoin (DPH) in the daily diet (liquid diet 'Stardit', supplemented with vitamins) over a period of 8 weeks. Control and experimental animals were pair-fed. Twelve mice of both groups were perfused via the left ventricle with glutaraldehyde. Representative samples of the cerebral cortex (area 3), cerebellum (vermis and deep cerebellar nuclei), thalamus, hypothalamus, and liver were embedded in araldite. Semi-thin sections and electron microscopy of the cerebellar vermis revealed marked dystrophic changes in the Purkinje cell axons. The presynaptic segments of Purkinje cell axons in the deep cerebellar nuclei showed massive enlargement and swelling due to accumulation of spherical particles and tubular structures in the axoplasm. These structures represent a proliferation of the smooth endoplasmic reticulum. Identical changes were found in hepatocytes of treated animals. Because phenytoin induces hepatic microsomal enzymes, we suggest that phenytoin related Purkinje cell damage may be produced by an induction of Purkinje cell microsomes with proliferation of the smooth endoplasmic reticulum which causes a swelling and enlargement of presynaptic segments of Purkinje cell axons in deep cerebellar nuclei. Chronic phenytoin administration to mice is a new model of phenytoin-induced encephalopathy and of distal axonopathy of cerebellar neurons. PMID- 4024873 TI - Succinic and malic dehydrogenase histochemical activities in cerebral, cerebellar and neostriatum sections incubated in presence of d-amphetamine. AB - The action of d-amphetamine on the histochemical activities of succinic and malic dehydrogenases in sections of cerebral cortex, cerebellum, and neostriatum has been studied. Meldola blue was used as an exogenous electron carrier in the histochemical reactions. The results have demonstrated that d-amphetamine increases the activity of the enzymes studied. PMID- 4024874 TI - Lead-induced permeability changes in immature vessels of the developing cerebellar microcirculation. AB - The ultrastructure and microcirculatory permeability changes of lead encephalopathy were studied in an animal model using horseradish peroxidase as an intravascular tracer. The fine structure of capillary sprouts in the developing cerebellar microcirculation of lead-poisoned rats were described. Immature vessels, characterized by the presence of endothelial sprouts, were found to have focal areas of endothelial injury with degenerating endothelial cells. These disruptions of the microcirculatory endothelium had tracer extending from the vessel lumen to the surrounding neuropil. The degenerating endothelial cells were found as early as 24-28 h after the first administration of lead acetate by gastric lavage (2-3-day-old rats). The early injury to endothelial cells of immature vessels in the developing microcirculation is suggested as an important component of the vascular permeability changes which characterize lead encephalopathy. Older animals (5-10 days old) had microaneurysmal vascular dilatations which had a complex internal structure formed by endothelial cells. These microaneurysmally dilated vessels may represent an endothelial response to preceding endothelial injury of immature vessels. PMID- 4024875 TI - A quantitative study of blood-brain barrier permeability ultrastructure in a new rat glioma model. AB - Cerebral edema, a major complication of tumors in the brain, is the result of an alteration in the blood-brain barrier (B-BB). The vascular ultrastructural changes that underlie edema formation have been described in a variety of tumors. Interendothelial junction abnormalities, fenestrations, and large numbers of tubulo-vesicular profiles in the tumor vascular endothelium have been presumed to represent permeability routes that permit the escape of serum constituents into the tumor, from where they flow into the surrounding brain. Descriptive studies do not provide information on the relative frequency of these presumptive permeability routes. In the study reported here we have quantified ultrastructural features associated with the B-BB in the vessels of an experimental glioma in rat. We found that approximately 60% of the tumor vessel profiles have junctional abnormalities and 30% have one or more fenestrations. The density of tubulo-vesicular profiles, however, was not increased. In addition, tumor vessel walls were thicker than normal vessels of the same caliber and the mitochondrial density was in the range of that for non-barrier vessels. Vessels in peritumoral regions were not altered in any of the parameters measured. PMID- 4024876 TI - Cohort trends in incidence of cervical cancer in Denmark in relation to gonorrheal infection. AB - In England & Wales and in Scotland an association has been found between the cohort pattern in mortality for cervical cancer and gonorrheal infection, used as indicator of sexually transmitted diseases in general. An equivalent association could not be found in the United States. In Denmark a peak in gonorrheal infection was observed towards the end of World War II. The maximum level attained in Denmark was higher than reported from the other countries; in Copenhagen the attack rate was 3.3 times the rate for the rest of Denmark. Incidence data on cervical cancer in Denmark are available from 1943 to 1977. The 1918-27 birth cohort is assumed to be the one most heavily affected by the gonorrhea epidemic during the war. Incidence data accumulated over a broad age span show no general excess risk of cervical cancer for women born 1918-27, but the incidence is increased for this cohort 15-20 years after the gonorrheal infection. The cervical cancer rates are higher for women in Copenhagen than for all Danish women, but the excess risks for the affected cohorts are less systematic here. The limited size of the population in Copenhagen, migrations, and an intensive screening are possible explanations for the divergence between the results for all of Denmark and for Copenhagen. The study indicates an association in Denmark between sexually transmitted diseases and cervical cancer, and the study shows the importance of taking the risk-modifying effect of screening into account in studies of etiology for cervical cancer. PMID- 4024877 TI - Screening in pregnancy with unconjugated estriol compared with total estriol. AB - An obstetric population was screened 'blind' by measuring unconjugated estriol (ucE3) and total estriol (tE3) in serum. The purpose was firstly to ascertain the predictive values of ucE3 for the prediction of low birth weight and distressed neonates (perinatal deaths included), and secondly to compare the predictive values of ucE3 and tE3. The main material consisted of 1018 singleton pregnancies with known term, who would not have undergone estriol (E3) measurement had it not been for this investigation. The study was carried out prospectively, and the obstetricians had no knowledge of the E3 values in the screened pregnancies. When at least one of the ucE3 values was low, the risk of having a small for gestational age (SGA) infant was 22%. Low tE3 implied a 27% risk. When both were low, the risk of a SGA infant was 54%. The percentages of SGA infants found were 18, 19, and 12%, when ucE3, tE3, or both respectively, were low. ucE3 does not appear to be superior to tE3. From the predictive values found in this study, screening of a total obstetric population with ucE3 and/or tE3 cannot be recommended. PMID- 4024878 TI - Correlation between 2,3-diphosphoglycerate and red cell mass in the third trimester of pregnancy. AB - In 30 non-anemic, and in 7 non-thalassemic, anemic pregnant women the red cell mass (RCM) was determined at 32-36 weeks of pregnancy, using isotopes, and was correlated with red cell 2,3-DPG, using the method of Keitt. The increase in 2,3 DPG in pregnant women with low RCM was in the same range as in those with increased RCM. Thus, 2,3-DPG can not be used to diagnose a RCM deficit in pregnancy. The relationship between 2,3-DPG and RCM in the third trimester was complex: in the 7 anemic women there was an inverse relationship, which failed to reach statistical significance, probably because of the small number of cases; in the 30 non-anemic women there was a significant, positive correlation between 2,3 DPG and RCM. The cause of this positive relationship needs further investigation. PMID- 4024879 TI - Comparison of cellular levels of steroid receptors in uterine leiomyoma and myometrium. AB - To support the estrogen hypothesis in the pathogenesis of leiomyoma, total cellular estrogen receptor (ER) levels (the sum of levels in cytosol and nuclear KCl-extractable and nuclear non-KCl-extractable fractions) were assayed and compared with levels of progestin (PR) and androgen (AR) receptors in the leiomyoma and the corresponding myometrium. The ratios of ER to PR or AR levels were higher (with statistical significance) in leiomyoma than in the corresponding normal myometrium, both in terms of total cellular levels in each individual case and nuclear levels. It appears that estrogen sensitivity is higher in the leiomyoma than in the corresponding myometrium, due to the relative increase in ER. PMID- 4024880 TI - Rupture of the uterus in labor. A review of 96 cases. AB - Ninety-six cases of ruptured uterus in labor treated in the University Teaching Hospitals, Benghazi, Libya between 1977 and 1980 are reported. An incidence of 1 in 585 deliveries remained unchanged during the period of study. Twenty uterine ruptures occurred in a previously scarred uterus. Rupture of the unscarred uterus is a more catastrophic event. There is a marked difference in both fetal and maternal outcome between the group with a previously scarred uterus and the group without a previous scar. The incidence and causes of uterine rupture in Libya differ greatly from those in developed countries. High parity is a frequent cause. Other common etiological factors were cephalopelvic disproportion, fetal malpresentation, oxytocin stimulation of labor and unwise obstetrical interference. The fetal wastage was high, a perinatal mortality of 75% being recorded, but 95% of the mothers were saved. Hysterectomy was commonly performed in this group. Repair of the uterus and sterilization should only be performed when the rupture is simple and transverse in the lower segment and without any sign of infection. PMID- 4024881 TI - Males born in breech presentation 18 years after birth. AB - Forty-two singleton males in breech presentation born vaginally in 1962-63 were re-examined 18 years later at the medical draft board. Compared with all Norwegian conscripts of the same birth cohort, the study group exhibited no statistical difference as regards mortality, morbidity or general intelligence levels. PMID- 4024882 TI - Bladder tumor as apparent cause of vaginal bleeding in pregnancy. AB - The purpose of publishing this case story concerning macroscopic hematuria during pregnancy, is to draw attention to causes of bleeding in the pregnant. The cause in this case was found to be a papillomatous tumor originating from the bladder. This is emphasized as a possibility in the differential diagnosis from other causes of hemorrhage during the third trimester. PMID- 4024883 TI - Intra-uterine fetal death and thrombosis of the umbilical vessels. AB - Intra-uterine fetal death associated with thrombosis of the umbilical cord vessels is a rarely described condition. Three cases are now reported and the possible genesis of the thrombosis is discussed, with particular regard to the significance of disturbances in the fetal circulation. PMID- 4024884 TI - An unusual case of cervical pregnancy. AB - A very rare case of an unruptured cervical pregnancy, diagnosed by vaginal examination is described. An elective abdominal hysterectomy was performed. No complications related to this entity occurred during treatment. Clinical management and literature are discussed. PMID- 4024885 TI - Torsion of the fallopian tube during pregnancy. AB - We describe 3 cases of torsion of the Fallopian tube during pregnancy, caused by sactosalpinx, a cyst of the mesosalpinx, and an ovarian cyst. Other causes of torsion of the Fallopian tube are discussed. The difficulty of diagnosing this condition during pregnancy is emphasized. PMID- 4024886 TI - Harmonic versus impulsive acceleration testing of the vestibulo-ocular reflex in normal humans. AB - Vestibulo-ocular reflex (VOR) was tested in 9 normal humans by using both harmonic (sinusoidal) and impulsive (post-rotatory) angular accelerations. VOR gain and main time constant were 0.49 +/- 0.20 and 15.48 +/- 2.26 s, respectively, when computed from sinusoidal responses, 0.45 +/- 0.17 and 14.28 +/ 3.07 s when computed from impulse responses. Paired comparison could not prove statistically significant differences between the two sets of data. The conclusion is drawn that, in normals, equivalent information about VOR static and dynamic characteristics can be derived from either harmonic acceleration or post rotatory tests. PMID- 4024887 TI - Three-year results of combined modality therapy in locally advanced, resectable squamous cell carcinoma of the head and neck. AB - Results of a combined therapy, consisting of preoperative chemotherapy, radical resection and postoperative irradiation, of 51 locally advanced, previously untreated, resectable squamous cancers of the head and neck are reported. The overall response rate to chemotherapy was 58.5% (with 33% complete remissions) and higher in carcinomas of the oral cavity and hypopharynx than of the supraglottis and oropharynx. Three year survival was 53% for the entire group, 75% for hypopharyngeal, 58% for oral, 50% for supraglottic and 32% for oropharyngeal lesions, in responders to chemotherapy statistically significant higher than in non responders and only 18% in the fifteen patients who developed recurrences. PMID- 4024888 TI - Reconstruction of the airway with a composite alloplastic and autogenous graft. An experimental study. AB - A method by which an alloplast can be lined with mucosa and thereafter used as a composite pedicled graft is described and discussed. Autogenous buccal mucosa was transplanted to the pretracheal region in five beagles. Subsequently a cyst developed in which the graft constituted the main part of the cyst wall. After 5 to 6 weeks the cyst was explored and a Proplast sheet was sutured to its exterior. After another 3-9 weeks the area was explored again. A composite graft had then formed comprising buccal mucosa on the outside, stabilized by Proplast and supplied by blood vessels arising from the strap muscles and their fascia. After opening of the cyst, the composite graft was used to repair a tracheal defect in the same dog. All of the dogs survived and they did not lose any weight. The graft areas were removed 5 1/2-9 months after the tracheal window repair. Tracheoscopy was performed at least twice on each dog. The grafted areas were also studied by light microscopy, scanning electron microscopy and transmission electron microscopy. The grafts survived in all cases. There was no tendency towards graft extrusion. Connective tissue cells predominated in the pores of the Proplast framework, in which small foci of metaplastic bone formation were also seen. PMID- 4024889 TI - Late complications after irradiation treatment for cervical adenitis in childhood. A 60-year follow-up study. AB - Irradiation against benign cervical adenitis in children was formerly a widely used form of treatment which has caused a great number of late complications, mostly various benign and malignant tumours in the head and neck area, especially in the thyroid gland. In a follow-up study on 63 individuals irradiated at Karlstad Hospital between 1917 and 1929 we found, in addition to these changes, two hitherto not reported complications. Laryngeal stenoses occurred in 27 cases, 17 of which so severe that they eventually required permanent tracheostomies and 11 had fibrous strictures of the upper esophagus, repeated dilatations have been necessary in many of these cases. These complications were mostly seen in those who had been irradiated at an early age, the laryngeal stenoses appear to be caused by a general retardation or inhibition of the normal growth of the laryngeal cartilages resulting in a microlarynx. One possible explanation for these previously not reported sequelae might be the exceptionally high irradiation doses these persons were exposed to up to 60 years ago. PMID- 4024890 TI - The recovery of vascular changes following brief noise exposure. AB - Histological measures of cochlear vasculature and blood flow were examined in 20 guinea pigs. Sixteen were exposed to octave band noise at 120 dB SPL for 30 min and then permitted to survive after the exposure for 6 h, 18 h, 48 h, or 4 weeks (N = 4 in each group). Control animals were exposed to the laboratory and apparatus but not to the noise and then sacrificed after 48 h (N = 2) or 4 weeks (N = 2). Statistically significant results indicate that the noise exposure resulted in reduced RBCs in the cochlea for animals permitted to survive 6 to 18 h after the noise exposure. These changes, however, were no longer apparent in animals which were permitted to survive 48 h or 4 weeks after the noise exposure. The vascular sequelae of 30 min exposure to 120 dB octave band noise appear to recover within a few days of the exposure. PMID- 4024891 TI - A ferritin-containing cell type in the stria vascularis of the mouse inner ear. AB - This report describes a new cell type within the stria vascularis of the mouse inner ear. The cell is similar ultrastructurally to the classically described intermediate cell. However, it can be distinguished by the presence of dense vacuoles, presumably lysosomes, within which can be visualized electron dense particles resembling ferritin molecules. In addition, the ferritin-like particles are present throughout the cytoplasm and occasionally within the endoplasmic reticulum. These cells characteristically abut capillary basal lamina. Electron probe analysis of the dense vacuoles revealed the presence of iron. It is suggested that these cells may sequester iron released from dying erythrocytes in the strial capillary system, whereupon the iron is conserved through ferritin synthesis. PMID- 4024892 TI - Prediction of post-operative middle ear pressure changes after general anaesthesia with nitrous oxide. AB - There has been a growing interest in the changes of pressure which occur in the middle ears of patients undergoing general anaesthesia. In this study the time course of middle ear pressure change was investigated in 38 adult E.N.T. patients scheduled for surgery under general anaesthesia with nitrous oxide. There was found to be a strong correlation between the magnitude of the post-operative middle ear pressure and the theoretical partial pressure of nitrous oxide within the middle ear cleft at the cessation of anaesthesia. The use of the mathematical model developed together with measurements of middle ear pressure taken for several minutes after intubation in any one patient allows prediction of the likely magnitude of the post-operative middle ear pressure change. PMID- 4024893 TI - Histology of the tympanic perforation and the replacement membrane. AB - This study shows that the mucocutaneous junction of a perforation of the tympanic membrane may be located at the margin, in the middle ear, or in the ear canal. It is incumbent upon the surgeon performing myringoplasty to identify this junction in order to optimize the success of surgery. About one-third of the healed area following perforation has an intermediate fibrous layer. The membranes in 2 cases of myringoplasty evidenced thicker-than-normal intermediate layers. PMID- 4024894 TI - The effect of the rotational magnification of corrective spectacles on the quantitative evaluation of the VOR. AB - The gain of the vestibulo-ocular reflex (slow-phase eye velocity/chair velocity, measured in the dark) was compared in 11 normal healthy subjects who habitually wore corrective spectacles of varying strength. The rotational magnification (or prismatic effect) induced by habitually wearing corrective spectacles caused the VOR gain measured in darkness to vary systematically with diopter of correction. Even when allowances were made for the inherent variability of measurement of the VOR gain, myopes tended to have lower gains and hyperopes higher gains. This study demonstrates that the clinician should account for spectacle adaptation to properly interpret the results of vestibular function tests. PMID- 4024895 TI - Neurological evidence for dissociation of pursuit and optokinetic systems. AB - Patients with neurological disease were examined for dissociations between the performance capabilities of pursuit, immediate onset passive and active optokinetic responses to determine whether these functions are subserved by separate mechanisms. We found a patient in whom pursuit was intact in the presence of severely impaired optokinetic responses and another in whom optokinetic responses were intact in the presence of severely deranged pursuit. These dissociations suggest that pursuit and immediate onset optokinetic responses are mediated, to some extent, by separate mechanisms as the results are not explicable in terms of a continuum of performance ability related to target size. Another patient, who had virtually no pursuit or passive optokinetic responses, produced high slow phase velocities of active optokinetic response, which demonstrates that the active form of optokinetic response can be more than a linear addition of pursuit and passive optokinetic responses. PMID- 4024896 TI - The effect of lateral head tilt on horizontal postrotatory nystagmus I and II and the Purkinje effect. AB - The influence of an active lateral head tilt on postrotatory nystagmus I and II (PI, PII) was explored in normal humans. During postrotatory nystagmus the head was tilted laterally either towards the direction of the previous rotation (ipsilateral tilt) or towards the opposite direction (contralateral tilt) or the head was kept erect. Both ipsi- and contralateral head tilts led to a substantially weaker and shorter PI and PII as compared with the trial without head tilt. The time constants of the decline of PI were shortened to the ones observed in the peripheral nerve of animals. The reduction of PI and PII suggests a position-dependent tonic inhibition of the vestibular storage mechanism in the vestibular nuclei probably by the otoliths. The stronger reduction of time constant and cumulative amplitude of PI after contralateral as compared with ipsilateral head tilt may be explained by different combinations of asymmetric responses in canal and otolith afferents. PMID- 4024897 TI - A comparison of different methods for assessing the 'intensity' of tinnitus. AB - Questions are raised about the technical and psychological interpretation of loudness match measures in the assessment of tinnitus "intensity". The effect of hearing threshold on loudness matches expressed in sensation level (SL) was investigated by selecting subjects with different degrees of hearing loss. The loudness match expressed in SL was found to be a function of threshold. Correlations were then determined between psychological scales of tinnitus complaint (reported loudness, distress, intrusiveness, and others) and loudness match expressed in HL, SL, sones, or personal loudness units (PLUs). Only matches expressed in PLUs were significantly correlated with reported loudness or other psychological scales. The PLU transformation, derived from an individually determined loudness function, produces values that are generally independent of other audiometric measures. It is therefore recommended for assessing tinnitus "intensity". PMID- 4024898 TI - Detection of normal-hearing carriers of the gene for the autosomal dominant progressive sensorineural hearing loss. AB - Normal-hearing carriers of genes for autosomal dominant progressive sensorineural hypacusis can apparently be detected in families where this hearing disorder appears. In a group of 32 persons from four families, 13 carriers of the gene with subjectively good hearing and normal audiometric curves were found. Due to the pathologically elevated threshold of stapedial reflexes and in some cases to the presence of positive recruitment, these 13 persons fit in the clinical concept of an incipient disease. Beside these subclinical aberrations, the audiometric examination revealed a moderate to severe sensorineural hypacusis in 17 persons with already developed hearing impairment. Careful examinations with suprathreshold tests may enable us to detect carriers of the gene for autosomal dominant progressive sensorineural hypacusis; this circumstance can be utilized for establishing prognoses with respect to hearing function in the affected families. PMID- 4024899 TI - Hyperlipidemia and noise in the chinchilla. AB - Chinchillas were maintained on a 1% cholesterol diet for 6 months. Auditory Brainstem Response (ABR) measurements were obtained before and at 1, 3, 5, and 6 months after initiation of diet. Compound Action Potential (AP) measurements were obtained at sacrifice at 6 months. A significant reduction in ABR was seen at 5 months-on-diet. At 5 months, the animals were exposed to a 2 octave bandpass noise centered at 1 kHz at 105 dB for 220 min. One month following noise exposure, the cholesterol-fed animals exhibited a greater ABR latency shift at low intensities, and an elevated AP threshold at higher frequencies, vis-a-vis a control group. PMID- 4024900 TI - The developing electrolytes concentrations of inner ear fluids in guinea pigs. AB - Cochlear endolymph, scala tympani perilymph, and scala vestibuli perilymph were collected from fetal, neonatal, and mature guinea pigs. The concentrations of Na and K in these fluids were then assessed using a microflame photometer. The electrolyte composition in the endolymph was already characterized by a high concentration of K and a low concentration of Na by the 49th day of gestation. PMID- 4024901 TI - Auditory disorders following head injury in children. AB - 199 children with blunt head injury were examined. Eighteen fractures of the temporal bone were found, two of which were transverse. In both cases the damaged ear remained completely deaf. Of the 16 longitudinal fracture patients, one was left with a persistent 27 dB conductive hearing loss. In another, surgery revealed fractures of the stapedial crura. Persistent sensorineural hearing loss (greater than or equal to 30 dB) at high frequencies (4 to 8 kHz) was observed in 7% of patients. The results of the audiological tests led to the conclusion that sensorineural hearing loss in association with head injury is generally located in the inner ear. The auditory sequelae after head injury in children were found to be similar to those reported earlier in adults. PMID- 4024903 TI - Anatomical variations and relations of the bony portion of the eustachian tube. AB - The bony portion of the Eustachian tube was examined, using anatomical and histological methods, on 200 temporal bones of adults. This part of the tube averages 11.38 mm in length, its tympanic opening has an average diameter of 5.20 X 3.95 mm, and its lumen can be of an irregular (45%), rectangular (35%) or triangular (20%) shape. The dimensions of the bony portion of the tube diminish gradually toward the isthmus, so that in the middle the average diameter is 4.02 X 3 mm and at the level of the isthmus, 2.5 X 1.5 mm. The outer wall forms the tympanic plate of the tympanic bone, which in 65% of the cases is compact and in 35% finely pneumatized. On this wall bony trabeculae often appear, which more or less block the lumen of the tube. The medial part of the upper wall forms the bony septum toward the m. tensor tympani and the lateral represents the tegmen. The average distance from the lumen of the tube to the dura at the level of the tegmen is 3.62 mm. The tegmen above the tube may be pneumatized (45%) or compact (55%). The lower wall in 20% of the cases is represented by a shallow groove, and if formed is usually convex into the tube's lumen, but is less often concave. The jutting out of the lower wall is usually caused by its pneumatization. PMID- 4024902 TI - Cochlear blood flow studied with microspheres. A comparison between two different modifications of the microsphere method. AB - In albino rabbits, spontaneously hypertensive rats, and guinea pigs, cochlear blood flow was measured with the microsphere method, using radioactively labelled microspheres technique and a gammaspectrometer. This 'conventional' microsphere method was compared with a new technique for measurements of cochlear blood flow: a modification of the 'radioactive' microsphere technique and the soft surface specimen technique. Values obtained for cochlear blood flow by the two different methods were similar. Consequently, the microsphere surface technique is a suitable alternative to the classical radioactive microsphere method for blood flow determinations in the cochlea. PMID- 4024904 TI - Anatomical variations and relations in the medial wall of the bony portion of the eustachian tube. AB - The medial wall of the bony portion of the Eustachian tube was examined, by anatomical and histological methods, in 150 temporal bones of adults. This wall consists of two parts: posterolateral (labyrinthine) and anteromedial (carotid), whose shapes, sizes and relations depend upon the position of the a. carotis interna. If it is located nearer the tympanic opening of the tube, the labyrinthine part of the wall is smaller and has a triangular shape. The further the artery is removed from the tympanic opening of the tube, the greater and more rectangular the shape of this part of the wall. The part of the medial wall which corresponds to the a. carotis interna can differ in each case and in 69% of the cases this part extended more or less into the lumen of the tube. The average thickness of this part of the wall is 1.5 mm (minimum is wafer-thin and maximum is 3 mm). In 2% of the cases the bony wall above the a. carotis interna was missing, so that the artery projected into the protympanum. Through a bone defect, aneurysm of the artery can develop. In one case, during an operation, it was established that the protrusion of the a. carotis interna into the tympanic cavity was due to a defect in the medial wall of the Eustachian tube. PMID- 4024905 TI - Non-collagen proteins of stapedial bone matrix in perilymph of otosclerotic patients. AB - Non-collagen proteins extracted from the otosclerotic stapes footplate, superstructure and temporal cortical bone were compared with the protein patterns of normal and otosclerotic perilymph by analytical isotachophoresis (ITP). Normal and otosclerotic perilymph yielded basically identical isotachophoretic subfractions. Thirteen subfractions were detected moving as anions at pH 9.6 in the normal perilymph, versus 16 subfractions of similar character in the otosclerotic perilymph. Of these 16 protein subfractions, one (which was not detected in the normal perilymph) could be found in the ITP-gram of the stapes footplate non-collagen proteins, but not of the stapes superstructure or temporal cortical bone. Our results support the concept that protein can enter the inner ear fluid spaces from the otosclerotic bone. The biological significance of these proteins has not yet been clarified. PMID- 4024906 TI - The causes of asymmetry of the mastoid air cell system. AB - Starting from age 2 up to 7 years, 79 otherwise healthy children underwent nine tympanometric tests. At the age of 7, mastoid X-rays were obtained and the air cell areas measured by planimetry. The mean area was 8.4 cm2, with a left-right mean difference of 1.57 cm2. The children could be divided into three groups: (1) the ears with the smallest cell system associated with abnormal tympanograms (i.e. 'agreement'); (2) the ears with the largest cell system associated with abnormal tympanograms (i.e. 'disagreement'); (3) children with symmetrical cell systems and tympanograms. Significant majority of children showed 'agreement'. The results indicate that the size of the mastoid air cell system is determined by the degree of pathological involvement of the middle ear during childhood. PMID- 4024907 TI - Caloric vestibular test in the weightless phase of parabolic flight. AB - Twenty-four caloric vestibular tests were conducted in 20 test subjects during parabolic flight, in which weightless periods of about 10 seconds were elicited. The caloric nystagmus disappeared completely in all experiments in weightlessness, whereas in the higher G-periods the speed of the nystagmus increased. With regard to the modes of response during the periods with increased G-values prior to and following the weightlessness, four different types could be distinguished. In mode I the speed of the slow nystagmus phase increased in the higher G-periods, the nystagmus showed a prolonged duration, while in weightlessness it faded out completely. A reversed nystagmus appeared when the primary caloric nystagmus had disappeared. In modes II, III and IV the direction of the nystagmus reversed during weightlessness. In modes II and III this reversed nystagmus appeared even when the primary caloric nystagmus had disappeared. In mode III the nystagmus resembled the type of mode II, with the difference that it faded away much earlier than could be expected. In mode IV the primary nystagmus lasted rather briefly, while the reversed nystagmus during weightlessness was also much shorter. The experiments produced two remarkable facts: the appearance of a nystagmus reversal, a 'secondary nystagmus', in all experiments in weightlessness, and furthermore great differences in findings between the individuals as well as between experiments in the same person. The only explanation for the inconsistency in the findings is the assumption that effects on other canals, otoliths and vestibular nuclei are continuously changing and therefore interfere with the only endproduct measured, the horizontal nystagmus.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4024908 TI - Intervestibular integration and its clinical consequences. AB - Research during the last twenty years has led to the conclusion that it is time for a more integrated and dynamic view on the physiological and pathophysiological process during clinical vestibular stimulation and perhaps also to reevaluate the interpretation of the findings. Ten patients with absence of function in one labyrinth were exposed to caloric and rotatory stimulation several times during the compensating period of 8 weeks. In the acute state, caloric irrigation of the normal ear with 30 degrees or rotatory stimulation toward the damaged ear resulted in total inhibition of the spontaneous nystagmus. In the chronic state the same investigation reversed the spontaneous nystagmus in the opposite direction. The investigation has shown that it is possible clinically to study the reactions of every single neuron in the vestibular ocular reflex pathway and in this way establish a more topographic diagnosis. PMID- 4024909 TI - Transdermally administered scopolamine vs. dimenhydrinate. I. Effect on nausea and vertigo in experimentally induced motion sickness. AB - The effect of transdermally administered scopolamine (TTS-scopolamine) (2.5 cm2 surface area, one and two patches) and dimenhydrinate (100 mg) on experimental motion sickness was examined in 16 healthy volunteers in a randomized double blind study. Nausea was induced by Coriolis manoeuvre and vertigo by calorization of the ear. In all subjects, scopolamine was found in urine in concentrations indicating adequate absorption of the drug. One TTS-scopolamine, two TTS scopolamine and dimenhydrinate caused a statistically significant reduction in nausea when compared with placebo. Dimenhydrinate was somewhat more effective against nausea than one TTS-scopolamine. Vertigo was significantly reduced after dimenhydrinate and two TTS-scopolamine. Side effects of both drugs were negligible, though gait disturbances and vertigo could occur occasionally after two TTS-scopolamine. No dose-response relationship was found between the urinary excretion of scopolamine and alleviation of nausea. Dimenhydrinate and TTS scopolamine are both effective against motion sickness, the latter provided it is applied 6 to 8 hours before exposure to the stimulus causing the motion sickness. PMID- 4024910 TI - Transdermally administered scopolamine vs. dimenhydrinate. II. Effect on different types of nystagmus. AB - The effects of transdermally administered scopolamine (TTS-scopolamine) (release rate 5 micrograms/h, one and two patches) and dimenhydrinate (100 mg) on caloric, angular acceleration induced and optokinetic nystagmus were examined in 16 volunteers in a randomized double-blind study. All drugs induced a statistically significant decrease in maximum velocity of caloric nystagmus, as compared with placebo. In the rotatory test, two TTS-scopolamine and dimenhydrinate reduced the vestibular gain significantly. No changes were observed in time constant. In the optokinetic test, all drugs tended to reduce the responses, but a statistically significant reduction was found only after two TTS-scopolamine. The results indicate that the drugs effective against motion sickness reduce the nystagmic response, which at least partly explains the mode of action of the drugs. The target organ of the drugs is presumably the vestibular nucleus, where vestibular and visual impulses are integrated to ensure optimal gain for vestibular orientation reflexes. PMID- 4024911 TI - Activation of the impaired nasal mucociliary function. A preliminary clinical study. AB - The effect of HR-6 solution containing adenosine triphosphate 10 mg/ml on the impaired nasal mucocililary function in 13 patients was studied. The nasal mucociliary function measured with the radioisotopic method using 99Tc-labelled human serum albumin as a tracer substance was markedly impaired in all patients. The patients had had symptoms of upper and/or lower respiratory tract infections for 8 1/2 years, on the average. The nasal mucociliary function ranged from 0 to 5.0 mm/minute, mean 2.0 mm/minute. In this single dose study the test drug improved nasal mucociliary function by at least 1.4 mm/minute in 77% of the patients and by at least 2.8 mm/minute in 54% of the patients. This preliminary study indicates the need for further examinations with the HR-6 in patients with impaired mucociliary function. PMID- 4024912 TI - H1 and H2 histamine receptors in the in vitro nasal mucosa. AB - The effect of histamine was studied on canine nasal blood vessels with an in vitro muscle tension measuring technique. Observations suggest that histamine has at least four different effects: 1) inhibits the contraction induced by nerve terminal stimulation, 2) relaxes the smooth muscle under sustained contraction, 3) contracts the smooth muscle, 4) enhances (nor)epinephrine-induced contraction. Both H1 and H2 histamine receptors were identified in the mucosal blood vessels of the canine nasal septum. H1 receptors were present at the surface of vascular smooth muscle and mediated the contractile response (3) due to opening calcium influx channels. H2 receptors existed at both sympathetic nerve terminals and the muscle cell membrane. Stimulation of either H2 receptor caused muscle relaxation. The presynaptic H2 receptors mediated vasodilation through the inhibition of norepinephrine release from the nerve endings. Postsynaptic H2 receptors caused direct muscle relaxation possibly through an increase in cyclic AMP. Both H1 and H2 antagonists worked well, whereas agonists did not properly produce theoretically expected results in these specimens. PMID- 4024913 TI - Light and electron microscopy of varicose vessels and telangiomas in the nasal mucosa of habitual nosebleeders. AB - Biopsy specimens of abnormal vessels in the nasal mucosa of 42 habitual nosebleeders (22 with telangiomas, 20 with varicose vessels) were examined with light and electron microscopy. There were no specific morphologic features that distinguished the wall structure of solitary varicose vessels from that of telangiomatous lesions consisting of multiple vessel branches. Thus, in both categories of vascular malformations a disproportionately thin and simple wall lined the large lumina. Mostly, the endothelium was the only component in the wall. The endothelium could consist of extremely thin, seemingly degenerating, cells that at some points even failed to form a continuous tunic. At other areas of the same vessel circumference patches of thick, organelle-rich, 'active' endothelial cells could be seen and endothelial cells with intermediate structural characteristics were also found. It is suggested that these endothelial cell appearances represent different stages of cellular proliferation, maturation, and ageing, i.e. turnover. The periendothelial lamina was occasionally multilayered. The large, thin-walled abnormal vessels were covered with scarce connective tissue and a rather thin epithelium. For simple mechanical reasons it is obvious that bleeding, i.e. vessel wall rupture, is easily elicited in these vascular channels and that control of hemorrhage is defect due to the absence of a true muscular media. The findings give rise to interesting questions as to the initiation and control of the abnormal angiogenic response(s) in the nasal mucosa manifested clinically as recurrent epistaxis. PMID- 4024914 TI - Blood flow in the rabbit sinus mucosa during experimentally induced chronic sinusitis. Measurement with a diffusible and with a non-diffusible tracer. AB - Chronic sinusitis was induced in New Zealand White rabbits. Access to the sinus cavity in question was obtained through a hole drilled in the dorsum of the nose, and for induction of sinusitis either cotton wool together with a suspension of 10(8) Streptococcus pneumoniae was introduced, or this method was combined with blocking of the sinus ostium with methacrylate. In 9 rabbits (weight range 3.6 5.0 kg), blood flow was determined 5 weeks-9 months after the induction of sinusitis, at a point in time when heavy inflammatory signs were present. The blood flow was determined both with radioactively labelled microspheres 16 +/- 1.5 micron in diameter and with Rb86Cl. Cardiac output as determined with the microsphere method was 127 +/- 28 ml X min-1 X 1 000 g-1. The blood flow in the sinus mucosa was 0.60 +/- 0.16 ml X min-1 X g-1 with the microsphere method and 0.51 +/- 0.20 ml X min-1 X g-1 with use of Rb86Cl. These values did not differ significantly from the corresponding values found previously in healthy rabbits. PMID- 4024916 TI - Ultrastructural features of the adult laryngeal papilloma. AB - The ultrastructural features of nine laryngeal papillomas of the adult type were examined by transmission and scanning electron microscopy. The surface was covered by numerous microvilli varying in size and shape and often arranged in parallel cords. Although we did not find virus-like particles, the ultrastructural characteristics of the adult type of laryngeal papilloma did not differ from those previously found on the juvenile type. The two types may in nature be one and the same lesion, differing in behaviour because of the different environments. PMID- 4024915 TI - Nasal cuboidal metaplasia with dysplasia. Precursor to adenocarcinoma in wood dust-exposed workers? AB - The histological study of the non-tumours nasal mucosa in 22 wood-workers with ethmoidal adenocarcinoma was carried out and special attention was paid to the presence of cuboidal metaplasia with or without dysplasia. The workers had been exposed to wood dust for an average of 38 years (range 18 to 55 years). In 19 cases cuboidal metaplasia was found and 16 of these also had dysplasia. In 10 cases there was a transitional zone with dysplastic cuboidal epithelium in continuity with the tumour. In 5 cases there was squamous metaplasia. The results indicate cuboidal metaplasia with dysplasia being a possible precursor to nasal adenocarcinoma in workers exposed to wood dust, similar to the findings of squamous metaplasia and squamous cell carcinoma in nickel workers. PMID- 4024917 TI - [Otic acoustical discharges and their relation to tinnitus]. PMID- 4024919 TI - Breast feeding of low birthweight infants. AB - The incidence and length of breast feeding of LBW (less than or equal to 2500 grams) infants were investigated. A marked increase from 1979 to 1982 was noted: the incidence rose from 78% to 91% and the proportion of infants breast fed for 3 months rose from 54% to 67%. A breast feeding promotion programme did not influence the length of breast feeding of LBW infants within one year of the intervention. Smaller infants, those with RDS and those from lower social classes were breast fed less than others. PMID- 4024918 TI - Oral rehydration therapy in infectious diarrhoea. Comparison of rehydration solutions with 60 and 90 mmol sodium per litre. AB - The clinical response and changes in water and salt homeostasis as judged from serum sodium levels, salt and water retention and renal handling of sodium was studied during 36 hours following the start of oral rehydration therapy (ORT) with a solution containing 60 mmol Na/l (ORS60) in 17 well-nourished, moderately dehydrated Turkish infants aged 3 to 15 months who had acute infectious diarrhoea (7 with rotavirus, 3 with enteropathogenic E. coli 0 111: B 84, and one with enteropathogenic E. coli 0 125: B 15, one with salmonella and 5 of unknown etiology. In the successfully treated patients sodium and water balance was normalized within 36 hours. In the cases with hypernatremic dehydration the serum sodium concentration rapidly became normal. The results were compared with those obtained in a previous study of the same type of patients who were rehydrated with a solution containing 90 mmol Na/l (ORS90). Although retention was considered to be satisfactory after ORS60 it was less than after ORS90. The changes in the fractionary urinary sodium excretion and the potassium sodium quotient in the urine indicated a less rapid normalization after ORS60 than after ORS90. PMID- 4024920 TI - Carnitine in maternal and neonatal plasma. AB - Total plasma carnitine was analysed in 19 women, with uncomplicated pregnancies, who underwent elective caesarean section, and in their neonates. The women were given a balanced glucose (glucose group) or saline (saline group) infusion, group allocation being on a random basis. The carnitine levels in maternal or infant plasma did not differ between these two groups. At delivery, the mean maternal carnitine value, 17.4 +/- 1.25 mumol/l, was lower than the mean infant value, 25.9 mumol/l +/- 2.67 (mean +/- SE, p less than 0.005) and lower than the mean value in non-pregnant, fertile women, i.e. 40.9 +/- 1.22 mumol/l. The mean carnitine value in the unfed neonate had not changed when the infant was 4 hours old. A positive correlation was found between carnitine levels in maternal and infant plasma (p less than 0.01). At delivery, the levels of non-esterified fatty acids and 3-OH-butyrate in infant plasma were different in the two groups, but not at 4 hours of age. The results suggest that the maternal carnitine level is the most important factor governing plasma carnitine levels in the neonate. PMID- 4024921 TI - Benign infantile nocturnal myoclonus. AB - Myoclonic jerks during sleep is a normal phenomenon seen also in infancy. Sometimes the episodes can be extended both in duration and seizure type. When this happens it should be differentiated from epilepsy and treatment is not needed. Five cases are reported. PMID- 4024922 TI - Subclinical trace element deficiency in children with undue susceptibility to infections. AB - Serum concentrations of iron, copper, zinc and magnesium and also serum transferrin and ceruloplasmin were investigated in 28 children aged 10 months to 10 years with undue susceptibility to infections. None of the children had any classical immune defect. Seven of them had had frequent upper respiratory tract infections, 16 had suffered from frequent infections of the middle ear and five from mainly lower respiratory tract infections. Thirteen healthy children aged 9 to 18 years residing in the same area served as controls. The children with undue susceptibility to infections had significantly lower mean serum iron (p less than 0.05) and zinc (p less than 0.001) levels than the healthy controls. The mean serum concentrations of copper and magnesium and of transferrin and ceruloplasmin did not differ between the patients and controls. Children with frequent middle ear infections seemed to account for most of the differences in the serum levels of iron and zinc. An inverse correlation was observed between duration of breast feeding and serum concentration of zinc, and between weight as well as height and serum magnesium. The reasons for these changes and the possible role of trace element deficiency as a factor predisposing to or perpetuating undue susceptibility to infections in children are discussed. PMID- 4024923 TI - Catecholamine response to chest physiotherapy and endotracheal suctioning in preterm infants. AB - Adrenaline and noradrenaline was measured just before and just after chest physiotherapy and endotracheal suctioning in 13 preterm, ventilated, newborn infants. Mean aortic blood pressure was also recorded. Eight of the infants received phenobarbitone. Catecholamine levels were five-fold higher in the 5 infants with blood pH less than 7.30 compared to the other 8 infants. After the procedure, both adrenaline and noradrenaline were significantly higher than baseline levels. The adrenaline response to the procedure was a two-fold increase and significantly greater than the noradrenaline response. Analysis of the effects of phenobarbitone treatment and acidosis on catecholamine responses by multiple linear regression demonstrated that the adrenaline response was reduced by phenobarbitone while the noradrenaline response was unaffected. There were no associations of blood pressure, responses with catecholamine responses, with acidosis or with phenobarbitone treatment. PMID- 4024924 TI - Bile acid abnormalities and the diagnosis of cerebro-hepato-renal syndrome (Zellweger syndrome). AB - The Zellweger or cerebro-hepato-renal syndrome (CHRS) is a congenital disorder characterized by cerebral dysfunction, craniofacial dysmorphic features, transient cholestasis and renal cysts. Patients fail to thrive, and usually die in their first year of life. In some cases, a definite diagnosis on purely clinical signs might not be possible. Several biochemical abnormalities have been observed in these patients and some of them have been tested as diagnostic markers. The aim of this study is to evaluate bile acid metabolites as biochemical markers of the CHRS. From a study of 20 CHRS patients, we conclude that screening for the presence of coprostanic acids and the C-29 dicarboxylic bile acid in serum or urine is for detection of CHRS and confirmation of the diagnosis. PMID- 4024925 TI - The effect of multiple exchange transfusions on bilirubin binding. AB - Three bilirubin binding tests (hydroxybenzene-azobenzoic acid dye binding method, the estimation of unbound bilirubin by horseradish peroxidase assay and the saturation of albumin by the salicylate saturation index) were performed on pre exchange samples of blood and repeated 24 hours after the procedure. No significant improvement in bilirubin binding was found even in infants receiving as many as four exchange transfusions. Based on these bilirubin binding tests, we find no evidence that the criteria for subsequent exchange transfusions should be different from the first exchange transfusion. PMID- 4024926 TI - Serum and saliva Ig-levels in infants of non-atopic mothers fed breast milk or cow's milk-based formulas. AB - Of twenty-five healthy, full term infants without a family history of atopic diseases, 13 were exclusively breast-fed from birth for a minimum of 31/2 months (median 41/2 months), whereas the remaining 12 infants were fed with cow's milk based formulas from birth for a minimum of 4 months. In the latter group of children a significant increase in serum IgE as well as in salivary IgA was found. In infants exclusively breast-fed, no increase in serum IgE was seen until 6 months of age; at nine months of age, salivary IgA was still significantly lower than in the infants fed cow's milk-based formulas. No children developed obvious allergic diseases during the first three years of life. Thus, cow's milk proteins given to newborn children of non-atopic mothers did not seem to increase the risk of IgE-mediated diseases, maybe due to the development of "blocking" IgA antibodies in the alimentary tract. PMID- 4024927 TI - Tuberculin conversion following BCG vaccination in preterm infants. AB - Tuberculin conversion following BCG vaccination was evaluated in 3 groups of infants. Group I consisted of 12 preterm appropriate-for-gestational-age (AGA) infants given BCG vaccination at birth; Group II was made up of 15 term AGA infants similarly immunized while 8 preterm AGA infants (Group III) received BCG about the time estimated to be their normal birth-date. The tuberculin conversion rates of 83%, 93% and 88% in groups I, II and III respectively were not significantly different (p greater than 0.5). The results suggest that the preterm AGA infants born at 32-36 weeks of gestation can be effectively immunized with BCG at birth. PMID- 4024928 TI - Acute tubular dysfunction in infants with obstructive uropathy. AB - Eleven patients are described with severe hyponatraemia, hyperkalaemia and metabolic acidosis associated with a urinary tract infection and obstructive uropathy. This clinical entity resembles adrenocortical disorders. Urine culture investigation in combination with abdominal ultrasound examination will reveal urinary tract obstruction. Differential diagnosis, pathogenesis and treatment are discussed. In most patients correction of the metabolic disturbance can be achieved with antibiotic treatment, occasionally in combination with surgical therapy. Some degree of polyuria will generally persist. PMID- 4024929 TI - Myocardial ischaemia in asphyxia neonatorum. Electrocardiographic, enzymatic and histological correlations. AB - Serial electrocardiograms and creatine kinase (CK) isoenzyme activities were studied prospectively in 20 asphyxiated term newborn infants and 43 normal neonates. By adapting a previously described grading system for ischaemic changes, a degree of electrocardiographic ischaemia was defined which occurred almost solely in asphyxiated infants. Infants with this degree of abnormality had significantly higher mean CK-MB and MM activities than other asphyxiated infants at 0, 8 and 28 hours. Histological changes of peripartum myocardial necrosis were seen in 4 of the 5 infants on whom an autopsy was performed, and either electrocardiogram or CK-MB was abnormal in all four. It is concluded that myocardial injury in the newborn period is often associated with CK-MB release, but in view of the lack of cardiac-specificity of CK-MB in newborn infants, caution is urged in the interpretation of elevated isoenzyme activity in the neonate. PMID- 4024930 TI - Chlamydia trachomatis infection in a premature infant. PMID- 4024931 TI - False pathological thyrotropin (TSH) level in mother and infant caused by interfering antibodies in the TSH radioimmunoassay. PMID- 4024932 TI - Prognostic implications of functional hyposplenia in neonatal septicemia. PMID- 4024933 TI - Systemic amyloidosis in cystic fibrosis. PMID- 4024934 TI - Plasma valine and urinary C-peptide in infants. The effect of substituting breast feeding with formula or formula with human milk. PMID- 4024935 TI - Rotavirus infections among the staff of a general paediatric department. PMID- 4024936 TI - Pseudohypoaldosteronism in a female infant and her family: diversity of clinical expression and mode of inheritance. AB - Pseudohypoaldosteronism was diagnosed in an infant that clinically presented severe failure to thrive and vomiting. Evaluation of her extended family revealed many other affected family members with a vast range of clinical expression. The mode of inheritance is most likely autosomal dominant. Salt supplementation during infancy was effective in restoring normal growth, weight gain and serum electrolytes. PMID- 4024937 TI - Pseudo-precocious puberty caused by bilateral idiopathic testicular hyperplasia. AB - A boy aged two years presenting with advanced development of the genitalia, but with prepubertal testes, and accelerated growth is described. Investigation indicated pseudo-precocious puberty, due to idiopathic interstitial cell hyperplasia. Difficulties in interpretation of the hormonal studies were encountered due to an aberrant left testicular vein. This rare condition which has been called Testotoxicosis is probably due to an inborn error of metabolism not yet identified. PMID- 4024938 TI - Pathogenesis of portal sclerosis in the liver with idiopathic portal hypertension. Observations of 19 autopsy cases and animal experiments. AB - The pathomorphological changes of intrahepatic portal veins were studied in 19 autopsy cases of idiopathic portal hypertension (IPH), and the pathogenesis of portal sclerosis was discussed by the observations on the human and experimental materials. The degree and morphological appearance of intimal lesions vary from vessel to vessel. Fibro-cellular proliferation of subendothelial tissue and incorporation of organized mural thrombi were suggested as the cause of intimal thickening in the portal veins. Animal experiment showed that injury of portal vein wall was followed by intimal hyperplasia and/or incorporation of mural thrombi, and resulted in portal sclerosis similar to that of IPH liver. The cause of portal phlebosclerosis in IPH can not be explained by passive congestion alone. There might be a certain possibility of direct injurious effect in the vessel wall in the pathogenesis of portal lesions of IPH. The following pathogenesis of portal sclerosis in IPH is postulated: phlebo-sclerotic changes of the portal veins are initiated by injury to the vessel wall due to unknown cause(s) and accelerated by secondary thrombosis and/or mechanical injury due to increased portal pressure. PMID- 4024939 TI - Adrenal cortex of Micromys minutus japonicus (Japanese harvest mouse). Its histochemical and fine structural study. AB - Micromys minutus japonicus (Japanese harvest mouse) is one of the smallest known mammals and is easily maintainable in the laboratory. The adrenal cortex of this animal is described here for the first time. The morphological structure with histochemistry was essentially the same as that of the mouse or the rat. However, the histochemical activity of steroid 3 beta-OH dehydrogenase in the zona glomerulosa was characteristically positive in this animal and electron microscopically Golgi's apparatus and endoplasmic reticulum were prominent in the glomerular cells. The concentration of aldosterone was high in the serum. These findings suggest the hyperfunction of the zona glomerulosa in this animal. PMID- 4024940 TI - Cardiac disorders predisposing to development of cerebrovascular diseases in the Japanese. Data obtained at autopsy. AB - For a clear definition of the influence of cardiac disorders on the development of cerebrovascular diseases in the Japanese, we reviewed 1,162 consecutive autopsy records aged 20 years and over in the Department of Pathology, Kyushu University, Japan. All autopsies had been done between Nov. 1971 and Oct. 1981. Cerebral infarction was found in 101 out of 196 with any type of cardiac disorder. Frequencies of cerebral infarction in those with myocardial infarction, rheumatic heart disease, non-bacterial thromboendocarditis, and atrial fibrillation were higher than in those with no heart disease. These differences can be ascribed to the higher incidence of large and medium-sized cerebral infarction, including many cases of cerebral embolism originating from the heart. Only 3.4% of those with small cerebral infarction were assessed to be cases of embolism. Non-embolic cerebral infarction was more frequently noted in those with myocardial infarction and atrial fibrillation than in those with no heart disease. These differences were probably linked to concomitant progression of arteriosclerosis of the cerebral and coronary arteries. In this consecutive autopsy study, cerebral embolism was found in 35 cases, 10.9% of the total number of those with cerebral infarction. PMID- 4024941 TI - Gastric carcinoids of ECL cells. Pathological and clinical analysis of eight cases. AB - Clinical, histological, histochemical and ultrastructural characteristics of eight cases of carcinoid tumors of the non-antral portion of the stomach are presented. Four cases with multiple polypoid lesions are accompanied by an increased level of gastrin. A normal level of gastrin was present in the other four cases with isolated tumor and a normal component of endocrine cells in the uninvolved mucosa. In the first group with multiple lesions, the histological and histochemical analysis of the endocrine cells revealed a wide range of appearances: a) "simple hyperplasia", b) "nodular hyperplasia", and c) carcinoid tumor. These aspects suggested a different pathogenesis for the carcinoid tumors of the non-antral portion of the stomach with possible therapeutical implications. PMID- 4024942 TI - Minute carcinoma of the thyroid and its development to advanced carcinoma. AB - The relationship between the size of carcinomas and their histological characteristics such as encapsulation and sclerosis was studied using 157 cases of thyroid minute carcinomas with diameters less than 10 mm. When the diameter of the tumor was less than 1 mm, encapsulated carcinomas were not found, but they were presented in a group with a larger diameter. Sclerosing carcinomas were more frequently distributed in the group with a diameter less than 5 mm. With increasing tumor size, the carcinomas were reduced markedly in number and only two cases of sclerosing carcinoma were observed with a diameter more than 8 mm. It was concluded that thyroid minute carcinomas arise as nonencapsulated carcinoma, either sclerosing or non-sclerosing, followed by encapsulation at a later time and that some of the non-sclerosing carcinomas become apparent clinically, whereas most of the sclerosing carcinomas remain clinically silent throughout the entire life of the host. PMID- 4024943 TI - Familial occurrence of oligomeganephronia. AB - Oligomeganephronia (OMN) is a rare, renal hypoplasia, consisting of a reduced number of hypertrophied nephrons. This disorder has been considered to be a congenital but not a genetic disease. We describe the first report, to the best of our knowledge, of familial cases of OMN; two male siblings ran rapidly downhill courses and died 11 and 8 days after birth, respectively. In addition, the two patients had similar multiple anomalies; microcephaly, prominent glabella, hypertelorism, antimongoloid slant, epicanthal folds, broad nose, cleft lip and palate, down-turned mouth, short philtrum, micrognathia, low set ears, hypospadias, and cryptorchism. Although the patients and the parents had normal G banded karyotypes, 4p monosomy syndrome is suggested from clinical features. The implications of this are discussed briefly. PMID- 4024944 TI - Right-sided infective endocarditis combined with mitral involvement in a patient with ventricular septal defect. AB - An autopsy case of right-sided infective endocarditis combined with mitral valvular involvement in a 20-year-old male Japanese with ventricular septal defect (VSD) was reported. The vegetations were found on the endocardium bordering VSD, tricuspid valve, mural endocardium of the right ventricular outflow tract, and even the pulmonic valve, resulting in forming infective aneurysm of the pulmonary trunk. Streptococcus was morphologically identified in the vegetations obtained at autopsy. On the other hand, smaller vegetations were also noted on the mitral valve. The mechanisms of the mitral extending were discussed when right-sided infective endocarditis associated with VSD preceded that on the mitral valve. The authors think that mitral regurgitation in relation to VSD and right to left shunt through VSD which occur even temporarily may be the most important mechanism responsible for the mitral valvular involvement. Several differences between right-sided and left-sided infective endocarditis were also reviewed. PMID- 4024945 TI - Carcinosarcoma of the prostate. AB - The present report describes a rare prostatic tumor occurring in a 78-year-old Japanese male. The histological features were those of carcinosarcoma involving an adenocarcinoma and a chondrosarcoma, with metastasis to the liver. The carcinomatous component stained positively for prostatic acid phosphatase (PAP) by an immunoperoxidase technique. The literature is reviewed. PMID- 4024946 TI - Tubular adenoma with focal squamous metaplasia of the ascending colon. AB - A case of tubular adenoma with focal squamous metaplasia of the ascending colon in a 66-year-old male is reported. The tumor was a pedunculated polyp with a size of 1.5 X 1.4 X 0.9 cm. Histologically, the tumor showed tubular adenoma with moderate to severe atypia, was accompanied by focal squamous metaplasia. It is thought that squamous epithelial polyp may be derived from colonic adenoma with squamous metaplasia, and that the malignant change of colonic adenoma with squamous metaplasia may lead to squamous cell carcinoma, adenosquamous carcinoma, and mucoepidermoid carcinoma. Only seven cases of colonic adenoma with squamous metaplasia have been reported previously in the literature, and it is yet necessary to discuss the histogenesis, significance, and natural history of colonic adenoma with squamous metaplasia. PMID- 4024947 TI - [Effect of immune serum on the male Schistosoma japonicum subjected to pyquiton]. PMID- 4024948 TI - [Studies on the identification of the Chinese drug xin yi, the flower-buds of the Magnolia]. PMID- 4024949 TI - [Studies on the synthesis of 6,8-dimethyl-5,7,4'-trihydroxyl flavanone]. PMID- 4024950 TI - [Synthesis of some compounds related to tanshinquinone]. PMID- 4024951 TI - [HPLC and TLC-densitometry determination of alkaloidal constituents in Sophora flavescens and Sophora lopecuroides]. PMID- 4024952 TI - [Studies on 1H-NMR change at different temperatures and 13C-NMR T1 of polyphase liposome (139)]. PMID- 4024953 TI - [Studies on alkaloids isolated from Jiangyou fu zi (Aconitum carmichaeli Debx)]. PMID- 4024954 TI - Effects of acute and short-time antibiotic treatment on renal lithium elimination and serum lithium levels in the rat. AB - Male Wistar rats received a single stomach load (10 ml/kg) of a 150 mmol LiCl solution, either alone or together with tetracycline (33.5 mg/10 ml), ampicillin (33.5 mg/10 ml), or metronidazole (15 mg/10 ml). Urine was collected 1-5 hours after administration and blood samples were drawn after 1, 6, and 24 hours. All antibiotics caused a reduction in urinary lithium excretion but did not affect renal lithium clearance. Serum lithium levels were reduced by tetracycline and metronidazole 6 hours after administration but increased after 24 hours. Additional experiments including frequent mapping of serum lithium levels confirmed these findings. Tetracycline, also reduced renal sodium clearance and increased distal sodium reabsorption. Short-term daily treatment during one week with tetracycline or metronidazole showed that these initial changes were only transient, since after treatment for one week no differences could be observed between antibiotic-treated rats and control rats. The results indicate that antibiotics may cause a delay but no decrease of the gastrointestinal absorption of lithium and that they do not affect renal lithium clearance. Signs of lithium intoxication during combined use of lithium and antibiotics are therefore probably not caused by a renal interaction mechanism affecting the renal lithium clearance. PMID- 4024955 TI - Kinetics of disopyramide after intravenous infusion to patients with myocardial infarction and heart failure. AB - Total body clearance, half-life and volume of distribution of disopyramide (Norpace, Searle G.D.) was measured during a six to eight hour infusion to steady state in twenty four patients with either congestive heart failure or acute myocardial infarction and compared to eleven patients without these diseases. All patients were given a bolus injection of 150 mg disopyramide followed by a continuous infusion of 18-24 mg per hour. Serum concentration of disopyramide and its main dealkylated metabolite were determined by HPLC. The clearance in patients without myocardial infarction or congestive heart failure was 1.71 +/- 0.60 ml/min./kg (mean +/- S.D.), not significantly different from those who had either myocardial infarction, congestive heart failure or both. Half-life was 798 min. in patients without heart failure, not significantly different from the values in the other groups. The ratio between disopyramide and its metabolite varied between 3 to 10. Twenty-six % of the steady state serum concentrations of disopyramide were outside the recommended therapeutic range (2-5 micrograms/ml), but no adverse haemodynamic effects were observed in any of the patients. The suggested dosage regimen of disopyramide seems to result in a satisfactory response. PMID- 4024956 TI - Pharmacokinetics and pharmacodynamics of emepronium bromide (Cetiprin) after intravenous administration in man. AB - Intravenous doses of 1, 5, 10 and 15 mg of emepronium bromide were given to three healthy volunteers. Emepronium serum concentration declined in a triexponential manner with half-lives between 2.2-3.0 min., 1.0-1.6 hours and 5.1-13 hours, respectively. The initial dilution space (volume of the central compartment) varied between 4.1-7.5 l. The area under the serum concentration time curve increased linearly with dose, indicating constancy of total serum clearance (range: 24-38 l/hr) with dose. The renal clearance of emepronium varied with serum concentration; secretion in addition to glomerular filtration was evident. Tubular secretion of emepronium was half-saturated at serum concentrations of approximately 50 nmol/l. No obvious drug-related effect on blood pressure was noted, whereas salivary secretion decreased and heart rate increased with 10-15% at emepronium serum concentrations of about 200 nmol/l. ECG recordings were without abnormalities after slow intravenous injections of emepronium bromide in doses of up to 15 mg. Since no adverse effects were noted, intravenous administration of emepronium bromide may be an alternative in situations where the drug is now used intramuscularly e.g. severe tenesmus in the urinary bladder. PMID- 4024957 TI - The effect of indomethacin on the motility of isolated sheep ureters. AB - The possible spasmolytic effect of indomethacin was studied on isolated sheep ureteral preparations. Ureteral ring preparations suspended in an organ bath exhibited long lasting rhythmic contractions quite similar to the in vivo situation. This spontaneous motility was unaffected by hyoscine, phenoxybenzamine, propranolol, mepyramine and methysergide. Addition of indomethacin resulted in a dose dependent reduction in amplitude and frequency of the contractions, the threshold value being 10(-8) M. Washing reestablished motility and both PGE2 and PGF2 alpha were powerful stimulators of rhythmic contractions. Our conclusion is that in vitro rhythmic activity of the ureter is dependent on endogenous PG-synthesis and the cyclooxygenase inhibitor indomethacin dose-dependently blocks this. PMID- 4024958 TI - Effects of dinitrophenol on phosphorylase a activity, adenine nucleotide levels and tension in rabbit colon smooth muscle. AB - Glycogen phosphorylase a activity, the contents of adenine nucleotides and isometric tension were measured in rabbit colon smooth muscle after exposure to 2,4-dinitrophenol (DNP). DNP caused a dose-dependent increase in phosphorylase a activity, with an ED50 value of 1 X 10(-4)M. Since adenine nucleotides, especially 5-AMP by inhibiting the phosphorylase a to b conversion, might increase the phosphorylase a activity, a time-response study was undertaken in order to analyse the time course of changes in the adenine nucleotide content and phosphorylase a activity after addition of DNP. The latter activity was increased after only 1 min. of incubation. At this time no changes were found in the contents of ATP, ADP, 5-AMP or CP. Not until the phosphorylase a activity had reached its maximum after 5-7.5 min. did the 5-AMP content increase. The phosphorylase a activity then started to decline, but the 5-AMP content continued to rise. The effect of DNP on isometric tension was also studied to test whether the cytoplasmic Ca2+ concentration was increased. An increase in tension was observed 5 min. after administration of the drug and was maximal at 15 min. The results seem to dispute against 5-AMP as being a mediator for the DNP-stimulated increased in phosphorylase a activity in smooth muscle. The finding that DNP elicited a contraction of rabbit colon supports the earlier suggestion that the cytoplasmic Ca2+ concentration was increased (Pettersson 1983). PMID- 4024959 TI - The use of two different pharmacological principles to inhibit a cholinergic bronchospasm in guinea pig. AB - The ability of inhaled atropine and clonidine to inhibit a bronchospasm produced by injected acetylcholine or by vagal stimulation, was studied in anaesthetized guinea pigs. Vagally mediated airway constriction was restrained in a concentration-related fashion by inhaled clonidine and reached nearly 100% inhibition (EC50 = 2 X 10(-5) mol/l in the nebulizer). Atropine expressed initially about the same level of spasmolytic effect but only a final prevention of 60% was possible to reach with this drug. On the contrary, inhaled atropine was able to produce a complete inhibition (EC50 = 2 X 10(-6) mol/l) when the bronchoconstriction was elicited by exogenous acetylcholine. This type of spasm was also to some degree inhibited by clonidine. PMID- 4024960 TI - Changes in liver histology during methotrexate therapy of psoriasis correlated to the concentration of methotrexate and folate in erythrocytes. AB - To investigate, whether an assessment of the folate and methotrexate concentrations in erythrocytes could be used to indicate incipient histological liver changes, these 2 parameters were related to liver histology in series of liver biopsies (means 4.3 biopsies) from 31 long-term methotrexate-treated psoriasis patients. Logistic regression analysis showed that the probability of changes in liver histology during methotrexate therapy increased significantly with increasing erythrocyte methotrexate concentrations and with decreasing erythrocyte folate concentration. The application of these variables as a decisive criterion when to institute liver biopsy surveillance needs further studies, but can probably help reduce the number of liver biopsies to be taken during long-term methotrexate therapy considerably. PMID- 4024961 TI - Effect of toxic doses of progesterone on hepatotoxic effects of tetracycline. AB - The combined effects of high doses of tetracycline and progesterone on parameters indicative for liver function (serum transaminases and urea, serum and liver triglycerides and cholesterol) have been studied in mice. Apart from disturbance of cholesterol metabolism tetracycline-induced liver dysfunction was not aggravated by progesterone. PMID- 4024962 TI - Influence of dietary factors on aluminium absorption and retention in the brain and bone of rats. AB - Young adult male Sprague-Dawley rats were treated by gavage for 10 weeks (3-times weekly) with aluminium 100 mg/kg b.wt. in the form of Al-hydroxide (Novalucol), Al-citrate, Al-hydroxide together with citric acid or with tap water (controls). Male rats aged 13 months were gavaged for 11 weeks 3-times a weak with black currant soup (0.8 ml/kg b.wt.) stored 19 days in either aluminium or stainless steel saucepans. The brain cortex, bone and blood (young adults only) of each rat were analysed for Al using graphite furnace atomic absorption spectroscopy. The rats treated with Al-citrate and in particular rats treated with Al-hydroxide + citric acid showed a significant increase of Al concentrations in all the tissues studied. In the latter group the mean Al concentrations were elevated at 0.039 micrograms Al/g wet weight (controls 0.005 micrograms/g) 0.092 micrograms/g (0.016 micrograms/g) and 26.6 micrograms/g (0.22 micrograms/g) in the blood, brain and bone, respectively. After treatment with Al-hydroxide alone only the bone showed a moderate increase of Al-concentration. No significant differences were found in the brain and bone Al levels of the rats given fruit soup from aluminium saucepans (containing 17 mg Al/l) or stainless steel saucepans (0.4 mg Al/l). PMID- 4024963 TI - Effect of nicotine on passive avoidance behaviour and motoric activity in mice. AB - In this study the effect of different doses of nicotine (0.125; 0.250; 0.500 mg/kg) on motoric activity in mice was tested by a T-maze model both during dark and light phase of the diurnal cycle. Low doses of nicotine (0.125 mg/kg; 0.250 mg/kg) increased motoric activity during the day. During the dark phase no stimulation was seen. A higher dose of nicotine (0.500 mg/kg) decreased motoric activity both during dark and light phase of the diurnal cycle. A positive effect on retention time in a passive avoidance model was observed when mice were pretreated with 0.125 mg/kg nicotine. No significant effect was observed with 0.500 mg/kg nicotine. Thus, a low dose of nicotine which increases motoric activity also seem to have a positive effect on learning/memory mechanisms studied by a passive avoidance behaviour model. PMID- 4024965 TI - Aminolysis and hydrolysis of formanilide in water solutions. V. Influence of the substituent in para-position. PMID- 4024964 TI - Bioavailability of chloroquine in mice infected with the intestinal trematode Echinostoma revolutum. PMID- 4024966 TI - Antidiarrhoeal properties of Dorstenia drakena L. PMID- 4024968 TI - Synthesis of 2-methoxybenzylpyrrolidines of analgesic potential. PMID- 4024967 TI - Biopharmaceutical studies on pyridinolcarbamate. V. Effect of repeated administration of pyridinolcarbamate on the renal excretion of sulbenicillin in rabbits. PMID- 4024969 TI - X-ray powder diffraction data for propantheline bromide. PMID- 4024971 TI - Offspring of women with nonorganic psychosis: mother-infant interaction at three and-a-half and six months of age. AB - Mother-infant interaction during feeding and in an unstructured play situation was studied in the home at 3.5 and 6 months of age in index mother-infant pairs in which the mother had a history of nonorganic psychosis (n = 48 and 52 at 3.5 and 6 months, respectively) and in demographically similar control pairs (n = 80 and 79). Interaction was significantly more negative in index than control cases at both ages, index cases showing decreased maternal and infant social contact and reduced maternal sensitivity to the infant's needs. Schizophrenic and Cycloid groups evidenced more negative interaction characteristics than did their matched controls, while the Affective group was not generally more negative than its controls. PMID- 4024970 TI - The cultural perspective of therapeutic relationship--a viewpoint from Africa. AB - Therapeutic relationship has been considered an important ingredient of all psychotherapies. In communities in which no familiar conventions of such a relationship are available, the therapeutic encounter poses very different problems from those in the West, where such conventions freely prevail. This study has been carried out by five therapists representing three widely disparate cultures, but all working together in Tanzania. It brings together their perceptions of these problems and the strategies they employed to resolve them while working with African patients. In their view, in spite of great disparity between the world view behind Western psychotherapy and that of African communities, it is not impossible to forge a therapeutic relationship if empathic understanding and cultural sensitivity are added to the attitude of acceptance. After all, the therapist must attract and keep the patient before he can expect anything from him. The authors describe how this can be done with African patients. PMID- 4024972 TI - Stability of coping style 33 years after prolonged exposure to extreme stress. AB - Respondents who were in hiding or in the armed resistance movement in Nazi occupied Europe are assumed to have had avoidant and confronting coping styles, respectively. Responses to questionnaire items tapping behavior, attitudes and perceptions were examined in the two groups for the persistence of these same traits 33 years after World War II, in a study of randomly selected community sample of Jews. Taken as a whole, but not individually, responses to the questionnaire items suggested that the traits did persist (P less than 0.001). The results highlight the importance of distinguishing individual differences in coping style when studying the long-term effects of prolonged, stressful experiences. PMID- 4024973 TI - Suicides among male Finnish seafarers. AB - On analysing death registers of Finnish seafarers, 117 cases of suicide were found among active professional males in the years 1965-77. The suicide rate of the officers was similar to that of occupationally active males in the general population, while the suicide rate of the crew was 2 1/2 times higher (P less than 0.05). Many of the men who committed suicide had been at sea 5 to 10 years. Before their death they frequently changed ships. PMID- 4024974 TI - The intensive care unit and the suicide attempt patient. AB - Forty consecutively admitted suicide attempt patients, their 70 significant others, and the intensive care unit's personnel were interviewed about their feelings and reactions during the patients' stay on the intensive care unit. The patients belonged to three diagnostic groups. The most prominent feelings and reactions were shame and resistance towards the personnel in the neurosis group, anger and uneasiness in the abuse group, and indifference and apathy in the prepsychosis/psychosis group. The personnel did not observe the patients' underlying feelings and primarily responded to the patients' observable behaviour with different types of reactions, ranging from empathy to distancing and aggression. The latter reactions were due, in part, to the difficulties in dialogue between the patients and the personnel which aroused fear and anxiety in the personnel. The personnel's difficulties in communication with the patients, and the resulting problems are discussed. Significant others did not receive any support, in spite of their need for psychological help. PMID- 4024975 TI - Acts of violence in a traditional western Ethiopian society in transition. AB - The present study describes 316 consecutive cases of deliberately inflicted injuries attending a general hospital in western Ethiopia. One third of the cases concerned economic conflicts about land, cattle, etc., one third interpersonal conflicts in the family, between neighbours, etc., and one third were alcoholically intoxicated people who had been in a fight for no apparent reason. The incidence of homicide was estimated to be at least 5-12 per 100,000 inhabitants per year, which is somewhat high. The role of psychiatric disorders seems to be very limited. The most serious conflicts occurred in rural areas and were economic in nature. As this investigation was made during the imperial, feudal period, it allows a comparison to be made with the new conditions after the revolutionary changes in the economic system. PMID- 4024976 TI - Clinical and laboratory effects of discontinuation of lithium prophylaxis. AB - Twelve patients who met Research Diagnostic Criteria for a history of bipolar affective disorder gave informed consent for open discontinuation of lithium therapy for 3 weeks. There was no significant change after lithium discontinuation in the number of depressive or manic symptoms, in mood score, in total Zung Depression score, or in any of the 20 items found in the Zung Depression scale. There were significant reductions in total severity of side effects, and improvement in the three side effects reflecting renal function: polydipsia, polyuria, and nocturia. These changes were reflected in the significant increase in urine specific gravity. Significant changes in side effects did not take place until at least 2 weeks after lithium was discontinued. Other significant relationships were found between increases in serum thyroid hormone levels and in urine specific gravity, and decreases in Vmax of platelet serotonin uptake and increases in degree of clonidine-induced hypotension. PMID- 4024977 TI - Incidence of rheumatoid arthritis among patients with schizophrenia, affective psychosis and neurosis. AB - The aim of the study was to determine the incidence of hospital care with the diagnosis rheumatoid arthritis (RA) among patients with schizophrenia, affective psychosis and neurosis compared with that among hospitalized patients in general. By means of the in-patient register of Stockholm County, a cohort was formed comprising all patients discharged with the diagnoses schizophrenia, affective psychosis and neurosis in Stockholm County during 1971, and a sample of all patients discharged for any diagnosis during the same year. We followed the groups in the in-patient register through 1981 in order to identify hospital episodes with the diagnosis RA. Observed and expected incidences of RA in hospital care were obtained using all hospitalized patients as a reference group. For schizophrenia and affective psychosis the incidence of RA was around half the expected, whereas for neurosis it was close to the expected incidence. With reservation for small numbers of observed cases, the results support the hypothesis of a reduced incidence of RA among patients with schizophrenia. The finding regarding affective psychosis was based on a smaller number of cases and merits further investigations. PMID- 4024978 TI - Implications of the distinction between organic and functional psychoses. AB - On the basis of their symptomatology, some psychoses are called organic. The remaining psychoses are called functional. It is generally supposed that symptomatically organic psychoses have organic causes and thus call for medical investigations, while the functional psychoses are not so caused, and call for a dynamic formulation rather than an organic one. The author examines the basis for this distinction, and argues that it is logically unsound. He gives examples of exceptions to the rule, both organic-seeming illnesses that are the consequence of psychological mechanisms, and symptomatologically functional psychoses with organic antecedents. The exceptions prove to be so numerous that a different approach to the investigation of the psychoses, an approach stressing antecedents rather than symptomatology, appears to be called for. PMID- 4024979 TI - Mortality in the long-stay population of Dutch mental hospitals. AB - The cohort study by Giel et al. of mortality in Dutch mental hospitals is repeated. In the total cohort of 12,139 long-stay patients counted on prevalence day (31 December 1979) 1226 deaths occurred over a period of 2 years. Similar to the study of Giel et al. the overall death rate of long-stay patients in the 1979 cohort was approximately twice the expected death rates in the general population. The death rate of patients of both sexes and in each age group significantly exceeded the expected. In our study we found a different pattern of somatic causes of death. In the 1969 cohort respiratory disease was a major cause of death. In our long-stay cohort respiratory disease was a minor cause of death in all age groups. Another difference is the replacement of cardiovascular disease as a main cause of death by diseases of the cerebrovascular system. PMID- 4024980 TI - Representation of the orientations of shapes. PMID- 4024981 TI - Seeing and thinking. PMID- 4024982 TI - Perception and knowledge. PMID- 4024984 TI - The role of symmetry in shape perception. PMID- 4024983 TI - A neural network model of multistable perception. PMID- 4024985 TI - Knowledge within perception: masking caused by incompatible interpretation. PMID- 4024986 TI - [Evaluation of left ventricular function in a patient with angina pectoris by the determination of systolic time intervals]. PMID- 4024987 TI - Effect of a low-protein diet on the serum and liver lipid content of rats. PMID- 4024988 TI - [Parameters of renal insufficiency in aged patients with normal values of creatinine in the blood]. PMID- 4024989 TI - [Comparison of dysplastic changes in gastric stump mucosa in relation to the location of peptic ulcer surgery]. PMID- 4024990 TI - The meaning of the concept of the "transitional" group of oligodendrogliomas (a pathological and histochemical study). PMID- 4024991 TI - Determination of the onset of beta-methyl-digoxin action by potentiation of the adenosine response in guinea pigs. AB - The onset of beta-methyl-digoxin action was investigated by the potentiation of the adenosine response in guinea pigs and rats, and compared with that of digoxin and dipyridamole. A number of i.v. infusions of adenosine were given to determine the mean control adenosine response and its 95% confidence limits. After oral administration of the drugs, successive infusions of adenosine were continued until a drug-induced potentiation of the adenosine response was observed. The time of appearance of the potentiated adenosine response was marked as the onset of action of the drugs. The onset of action in guinea pigs was 9 to 12 min for 0.2 to 0.4 mg/kg of beta-methyl-digoxin, 90 to 100 min for 0.2 mg/kg of digoxin and 25 min for 5 mg/kg of dipyridamole. The maximal potentiation was 48.8 to 53.8% at 18 to 21 min for beta-methyl-digoxin, 74.5% at 130 min for digoxin and 74.8% at 80 min for dipyridamole. Adenosine infused i.v. into rats produced heart block, as in guinea pigs. However, in rats, the adenosine response was not potentiated by beta-methyl-digoxin and digoxin. Dipyridamole at a dose as high as 200 mg/kg produced 25.8% potentiation at 36 min after oral administration to rats. PMID- 4024992 TI - Evaluation of Talbot's safety zone of infusion volume and osmolality in infusion therapy for decompensated liver cirrhosis. AB - Problems with infusion therapy for correcting fluid and sodium imbalance in decompensated liver cirrhosis (DLC) were investigated by establishing the safety zone of Talbot et al. for parenteral fluid therapy in 4 DLC patients infused with over 900 ml of fluid each day for at least 9 days. The safety zone was different in each case. The safe infusion volume decreased and the safe electrolyte concentration shifted to a lower osmolality when there was ascites with renal failure than ascites without renal failure. Infusion therapy was performed without deterioration of the water and sodium balance in those patients whose infusion volume and fluid osmolality were in the safety zone. In contrast, ascites retention increased and peripheral edema appeared in patients whose infusion volume and osmolality were out of the safety zone. Therefore, the safety zone should be determined repeatedly during infusion therapy. PMID- 4024993 TI - Anteversion of the femoral neck in congenital dislocation of the hip. AB - A ten year follow-up study was made of 107 hips of 97 patients to find if derotation osteotomy affected the growth of the hip joint. The anteversion angles before and after treatment were measured in four groups classified according to treatment method: Pavlik harness, frog plaster, Colonna operation and derotation osteotomy. The difference in the angle was greatest in the derotation osteotomy group. However, no significant relation between the CE angles and the anteversion angles or the degree of derotation at the time of the follow-up study was found. The author concluded that the growth of the hip is not influenced by the extent of anteversion as much as was previously believed before. PMID- 4024994 TI - Adenosine triphosphate restoration and discocytic transformation of stored human erythrocytes. AB - Erythrocytes in human blood stored for 120 days were collected by centrifugation after dispersion in buffered physiological saline. The aged erythrocytes thus collected were incubated with inosine, adenine, glucose or other media, and their shapes and ATP levels were studied by scanning electron microscopy and a luciferine-luciferase method. The aged erythrocytes incubated in a mixture of adenine and inosine markedly regained their ATP levels, and also showed a marked transformation from spiked spherocytes to normal discocytes. Incubation with inosine alone restored ATP levels of the aged erythrocytes to some extent, but did not result in morphological rejuvenation. Incubation in a mixture of citrate and glucose caused morphological rejuvenation, though it restored ATP levels less effectively than incubation in inosine alone. Incubation with adenine alone neither restored ATP levels nor resulted in morphological rejuvenation of the stored erythrocytes. PMID- 4024995 TI - Clinico-pathologic analysis of 221 cases of breast carcinoma. PMID- 4024996 TI - [Compared hemodynamic effects of 4 inotropic agents used in a model of pulmonary edema due to oleic acid]. PMID- 4024997 TI - [Prognostic value of simple chest radiography for the establishment of risk factors in open mitral valve surgery]. PMID- 4024998 TI - [Revision of the academic curriculum during the clinical cycle]. PMID- 4024999 TI - [The infertile couple]. PMID- 4025000 TI - [N-acetyl-beta-D-glucosaminidase activity in relation to blood glucose, serum fructosamine and type I diabetic nephropathy]. PMID- 4025001 TI - Four-year incidence of myocardial infarction and sudden coronary death in twelve Finnish population cohorts. AB - The incidence of myocardial infarction (MI) and sudden coronary death in four years was studied in 6510 men and 5800 women, aged 30-59 years, derived from 12 Finnish population cohorts constituting the invited population to a prospective study. The incidence of all fatal coronary events in four years was 13.0/1 000 in men and 1.8/1 000 in women. The incidence of sudden coronary death was 7.8/1 000 in men and 0.7/1 000 in women. The incidence of non-fatal MI was 22.2/1 000 in men and 7.3/1 000 in women. Coronary mortality was significantly higher in non participants in the initial survey than in participants. The incidence of MI was highest in men from eastern Finland (North Karelia), intermediate in men from central and western Finland and lowest in men from southwestern Finland. There were no significant regional differences in the incidence of MI in women. The incidence of MI in this study was in good agreement with that recorded in the myocardial community registers. PMID- 4025002 TI - The prognosis for patients referred with suspected acute myocardial infarction. AB - A follow-up investigation of the prognosis of 381 patients admitted with suspected acute myocardial infarction (AMI) has been carried out in respect of later AMI or death. During hospitalization the patients were divided into groups with particular attention to patients with no demonstrable myocardial infarction but with ischaemic heart disease (non-AMI) and patients with confirmed AMI. All patients were subjected to follow-up for 43 months (range 37-54). The mortality from cardiovascular causes after four years was 26.2% of 130 non-AMI patients and 25.8% of AMI patients. The majority of new infarctions were found in the AMI patients, but with even increase in both groups, 50% occurring within the first 12 months. The groups were studied with regard to earlier manifestations of ischaemic heart disease and heart failure during hospitalization, without any difference being observed. Due to the poor prognosis the question is raised whether non-AMI patients as a group should be offered prophylactic therapy. PMID- 4025003 TI - Plasma HDL cholesterol and blood glucose in non-insulin-dependent diabetics related to liver lipids and microsomal enzyme activity. AB - The major lipid predictors of coronary events, plasma high density lipoprotein cholesterol (HDL-C) and the HDL-C/total cholesterol (T-C) ratio, and blood glucose (BG) in 12 subjects with non-insulin-dependent diabetes mellitus were related to hepatic lipids, proteins and microsomal enzyme activity assessed by liver cytochrome P-450 (P-450). Non-insulin-dependent diabetics had low HDL-C/T-C ratio, liver phospholipid (PL) and P-450 and high serum and liver triglyceride (TG) concentrations. Plasma HDL-C was decreased, and BG high, especially in subjects with reduced PL and P-450. The HDL-C/T-C ratio was directly proportional to liver PL and P-450 and unrelated to hepatic TG. Increases in liver PL and microsomal enzyme activity may be favorably reflected both in cholesterol distribution and diabetic control. PMID- 4025004 TI - Triglycerides--main lipid risk factor for cardiovascular disease in women? AB - A 12-year longitudinal population study of 1462 women, aged 38-60, was carried out in Gothenburg, Sweden in 1968-69. Women with high initial serum triglyceride values had a higher 12-year incidence of myocardial infarction, stroke and total mortality than the others. The findings for serum triglycerides persisted for myocardial infarction, stroke and total mortality after adjustment for other possible risk factors for ischaemic heart disease such as age, systolic blood pressure, smoking, indices of obesity and serum cholesterol, while serum cholesterol did not predict any end-points studied when taking other risk factors including serum triglycerides into account. PMID- 4025005 TI - Paradoxical esterification of plasma cholesterol in fish eye disease. AB - The activity of lecithin: cholesterol acyl transferase (LCAT), the enzyme which catalyses the esterification of human plasma cholesterol, has been measured by two independent methods in plasma from the two known living Swedish patients with fish eye disease. The enzyme activity was in both cases about 15% of that of normal plasma. Paradoxically, however, the percentage of plasma cholesterol which was esterified was almost normal in both patients. In addition, a normal spectrum of the fatty acids of the cholesteryl esters was present indicating a normal cholesterol esterification pathway in vivo. Incubation experiments in vitro of plasma from the two patients also yielded normal cholesterol esterification rates when measured by two different methods. These paradoxical results for cholesterol esterification are discussed on the basis of the present biochemical knowledge of fish eye disease and LCAT deficiency. PMID- 4025006 TI - Haemostatic parameters in Cushing's syndrome. AB - We have studied haemostatic parameters in 12 patients with Cushing's syndrome. Three patients had prolonged bleeding times, and in all seven patients whose bleeding times were measured 3-6 months after surgical treatment the postoperative bleeding times were shorter (mean 7.5 min) than the pretreatment times (mean 12.3 min). In ADP- or adrenaline-induced aggregation the second wave was lacking in six and the degree of aggregation was borderline or subnormal in five patients. One patient had, in addition, a severe defect in collagen-induced aggregation. However, thromboxane B2 production of the platelets from both endogenous and exogenous arachidonic acid was unaffected. Factor VIII:C, RAg and Rcof activities were all elevated, and in patients with severe disease F VIIIR:Ag and F VIII:Rcof activities were markedly more elevated than F VIII:C activity. The changes in both primary haemostasis and in factor VIII activities correlated clearly with the clinical severity of the disease. PMID- 4025007 TI - Abnormal renal sodium excretion in the nephrotic syndrome after furosemide: relation to glomerular filtration rate. AB - The effect of 40 mg furosemide intravenously on sodium excretion, the renin aldosterone system and arginine vasopressin (AVP) was studied in 14 patients with the nephrotic syndrome and in 13 control subjects. Creatinine clearance (Ccr) was reduced in all patients but four. Before furosemide, AVP, but not angiotensin II (AII) or aldosterone (Aldo), was increased in the nephrotic patients. After furosemide, sodium excretion (NaE) increased less and changes in AVP, AII and Aldo were blunted in the patients. Ccr and NaE were positively correlated in the nephrotic syndrome. The reduced sodium response after furosemide in the nephrotic syndrome seems to be closely correlated to a reduced glomerular filtration rate but not to an increased activity of the renin-angiotensin-aldosterone system. The reduced response of AVP, AII and Aldo after furosemide is consistent with a lower degree of volume depletion in nephrotic patients. PMID- 4025008 TI - Anti-acetylcholine receptor antibodies in primary biliary cirrhosis. AB - Low concentrations of acetylcholine receptor antibodies were found in 16 out of 17 patients with primary biliary cirrhosis. Seven patients were treated or had been treated with penicillamine. Ten untreated patients had antibody levels corresponding to those found in the treated group. Our data support the presence of receptor antibodies of both IgG and IgM class. PMID- 4025009 TI - Blood pressure changes in man during infrasonic exposure. An experimental study. AB - Twenty healthy male volunteers were exposed to infrasound in a pressure chamber especially designed for the experiments. The effects on blood pressure, pulse rate and serum cortisol levels of acute infrasonic stimulation were studied in a series of different experiments. Varying frequencies (6, 12, 16 Hz) and pressure levels (95, 110, 125 dB(lin)) were tested. Significantly increased diastolic and decreased systolic blood pressures were recorded without any rise in pulse rate. The increase in diastolic blood pressure reached a maximal mean of about 8 mmHg after 30 min exposure. The results suggest that acute infrasonic stimulation induces a peripheral vasoconstriction with increased blood pressure, previously shown to occur in conjunction with industrial noise. Chronic long-term exposure to environmental infrasound may be of importance for the development of essential hypertension in predisposed individuals. PMID- 4025010 TI - The significance of ST and T changes for the development of coronary events in patients with acute coronary chest pain, treated in a coronary care unit without verified acute myocardial infarction. AB - The one-year prognosis for patients with a confirmed diagnosis of acute myocardial infarction (AMI) was compared with that of non-AMI patients treated in the coronary care unit (CCU). The one-year incidence of coronary events (CE) after discharge from CCU was 37% in the 51 AMI patients and 20% in the 81 non-AMI patients. The one-year mortality rates were 27 and 4%, respectively. Among the non-AMI patients, well known risk factors such as hypertension, previous AMI, congestive heart failure, smoking, diabetes and hyperlipaemia were not more common in those who developed a CE. ST segment depression and T wave inversion, each of at least 0.1 mV, in three or more ECG leads were selective criteria for a high-risk group with respect to CE. Preventive measures should be considered in this group of patients without verified AMI. PMID- 4025011 TI - Prolonged severe cholestasis induced by oxacillin derivatives. A report on two cases. AB - Two patients with osteomyelitis who developed reversible cholestatic jaundice during treatment with oxacillin derivatives are described. The clinical course as well as the biochemical pattern and the investigation of liver biopsy specimens enabled us to establish the diagnoses of drug-induced canalicular and hepatocanalicular cholestasis. PMID- 4025012 TI - Severe proliferative retinopathy in a young man with diabetes of very short duration. AB - A 22-year-old man developed typical insulin-dependent diabetes mellitus. At the time of diagnosis no signs of diabetic retinopathy were found by an experienced ophthalmologist, but florid proliferative diabetic retinopathy was observed only seven months later. Despite treatment with laser and vitrectomy the eye lesions progressed to total blindness within 30 months after the diagnosis of diabetes. PMID- 4025013 TI - Treatment of supratentorial primary arachnoid cysts. AB - Twenty-four cases of supratentorial primary arachnoid cysts operated with different techniques are reviewed: both cyst shunting or extirpation may lead to a good early clinical result, but the former is less dangerous and more indicated in a particular group of patients; late results are better in the shunted patients. CT scan is almost always diagnostic and is mandatory postoperatively to assess the late results. PMID- 4025014 TI - Shunting procedures in the management of intracranial cerebrospinal fluid cysts in infancy and childhood. AB - Widely diverging opinions on the optimal therapy for intracranial cerebrospinal fluid cysts (CSF), mainly arachnoid cysts and the Dandy-Walker cysts, exist. Excision of the cyst walls in the treatment of the Dandy-Walker cyst has been replaced by shunting procedures, but the recommended method for primary treatment of arachnoid cysts in childhood is still cyst wall excision. Membrane excision is, however, often complicated by recurrence, subsequently requiring shunting procedures. In a series of 19 cases primary shunting of intracranial CSF cysts proved to be a reliable method. In those cases where hydrocephalus (ventricular dilatation) is present at the time of the primary operation the ventricles should be shunted as well as the cyst. The catheter from the ventricle and that from the cyst should be connected to the same valve, otherwise an increased risk of intracranial herniation exists. The prognosis for infants and children suffering from intracranial CSF cysts is in general good; in 17 out of 19 cases mental development was normal and in 15 out of 19 motor development was normal. The risk of permanent motor damage seems to be particularly high when an arachnoid cyst is located on the quadrigeminal plate. PMID- 4025015 TI - Gammasubdurography in the diagnosis of chronic subdural bilateral and communicating effusion in infants. AB - The results obtained by means of Gammasubdurography (G.S.G.) in 37 infants having chronic subdural bilateral effusions, are presented. The use of this procedure, which consists of unilateral injection of Radioiodinated Human Sero Albumin (RIHSA-I 131), into the subdural effusion, is suggested for the determination of a communication between the two cavities. At the same time it is possible to get valuable information about their exact localization and extension. Once the communication is diagnosed, the treatment proposed is internal or external unilateral drainage. The method is safe and is performed in a short time which permits its use in the screening of these patients, especially in conjunction with Gammaencephalography (G.E.G.) and Computer Tomography (CT), patients to it. The test (G.S.G.) has been used by us since 1979. All our cases are included in this series. All of them had been diagnosed by subdural puncture, transillumination, G.E.G. and or CT Scan, as having bilateral subdural collections. All the patients received a saturated iodine solution, 24 hours in advance and for 10 days, as a thyroid blocking agent, which was administered in the usual oral dosage. The radiopharmaceutical administration was performed through a unilateral subdural puncture in a dose of 50 to 80 microcurie of RIHSA I 131 with a high specific activity. Immediately after this, sequential analog images were obtained with the patient supine and in anterior and lateral head projections. This was accomplished by using a PICKER DYNA 4 Gammacamera equipped with a medium energy parallel hole collimator. The interval between the images was determined during the test in agreement with the findings. PMID- 4025016 TI - Tension pneumocephalus in association with ventriculoperitoneal shunt. AB - The authors report a case of tension pneumocephalus in association with a ventriculoperitoneal shunt for obstructive hydrocephalus, due to the presence of a pineal tumour. In this unique form of tension pneumocephalus, air from the middle ear must have penetrated into the brain parenchyma and later on into the ventricular system through pre-existing congenital defects in the bony tegmen tympani and the covering dura mater. The possible pathogenetic mechanisms of this kind of tension pneumocephalus are discussed. PMID- 4025017 TI - Spinal intradural arachnoid cysts. AB - Based on the study of 8 cases of spinal intradural arachnoid cysts, the authors underline that the diagnosis is sometimes difficult because of the limitations of the paraclinical examination. They discuss aetiopathological problems. PMID- 4025018 TI - Lancinating pain in post-laminectomy chronic sciatica. AB - Lancinating pain, as described in tabes dorsalis, was noted in four patients with chronic sciatica after several months of laminectomy. The pain responded well to carbamezapine therapy. Abnormal or ephaptic neural transmission of impulses in the roots was considered to be the cause of such pain. PMID- 4025019 TI - Creatine kinase BB in blood as index of prognosis and effect of treatment after severe head injury. AB - High concentrations of creatine kinase BB (CK-BB) were found in all blood samples drawn within 6 hours of accident from 45 patients with brain contusion. The highest concentrations of more than 100 microg/l were measured in blood samples taken shortly after the accident from patients with a Glasgow Coma Score (GCS) of 6 or less. The CK-BB concentrations decreased rapidly to normal within 36 hours of accident in the patients given intensive care guided by intracranial pressure (ICP) monitoring. In patients with less severe injuries according to GCS the initial CK-BB concentrations were generally lower and normalized less rapidly. The outcome after 6 months was moderate or good in all 9 patients who had this rapid normalization of blood CK-BB. On the other hand, of 20 patients who had a more slow CK-BB decrease, only 9 had an acceptable outcome. Delayed ICP increase to more than 40 mm Hg and even delayed brain tamponade did not result in CK-BB levels higher than 5 microg/l. Brain tamponade in the acute stage resulted in rapid CK-BB decrease in the blood. In paired simultaneously drawn samples of lumbar cerebrospinal fluid (CSF) and blood, CK-BB levels were generally higher in the CSF. PMID- 4025020 TI - Creatine kinaseBB-activity after head trauma related to outcome. AB - The brain-type isoenzyme of creatine kinase was determined in serum (S) and cerebrospinal fluid (CSF) in 37 patients with severe head injury, and a correlation was made with the Glasgow coma score and Glasgow outcome score. All patients with normal S-CKBB and CSF-CKBB activities had a coma score of 15, i.e., no neurological deficits, at six hours after the trauma and a good outcome. All 15 patients with a significant increase in the enzyme in serum and CSF had a coma score less than 15. The outcome was still good for five of these patients, while six were moderately disabled, two were severely disabled, and two died. There was no correlation between the individual CKBB-values and the outcome. PMID- 4025021 TI - Sub-pial infiltration of blood products following experimental subarachnoid haemorrhage. AB - The authors studied the trans-pial penetration of blood products into the cerebral cortex of cats within the first hour following subarachnoid hemorrhage (SAH). Twenty-two animals were subjected to SAH by cisternal injection of blood, and 13 were used as controls. The brains were fixed in situ and the histological sections were examined under the fluorescence microscope. The cerebral parenchyma of the control animals displayed a homogeneous greenish autofluorescence. In the animals with SAH, the subarachnoid blood showed a yellow autofluorescence that also penetrated into the superficial cortex. The possible clinical implications of the observation are discussed. PMID- 4025022 TI - Connective tissue scarring in experimental spinal cord lesions: significance of dural continuity and role of epidural tissues. AB - Neoformation of connective tissue occurring at the level of spinal cord injury is considered a factor in the failure of regeneration in the mammalian spinal cord. The purpose of the present research was to experimentally investigate the origin and characteristics of connective proliferation following spinal cord lesion produced by compression in the rat. The role of the dural sheath and that of the tissues surrounding the spinal cord were studied. In one group of animals (1), the dura mater was left intact; in a second group (2) a transverse incision of the dura was performed at the level of the spinal cord compressive lesion. In group (1) a few collagenous fibres were seen within the lesion but no connective septum was observed. In group (2) a transversely orientated septum of fibrous scar tissue was constantly found within the lesioned cord. Our experimental study shows that: 1. dural continuity prevents the formation of connective tissue scarring and limits fibrous reactions in the epidural space; 2. opening of the dural sheath is followed by a vigorous fibroblastic reaction in the epidural tissue which extends into the spinal cord to form a connective septum. PMID- 4025024 TI - Microsurgical anatomy around the origin of the ophthalmic artery with reference to contralateral pterional surgical approach to the carotid-ophthalmic aneurysm. AB - The supraclinoid segments of the internal carotid artery (ICA) and their surrounding structures were examined under magnification in 25 adult cadavers. Attention was paid to anatomical variations and relationships concerning ipsilateral and contralateral pterional microsurgical approaches to these regions, especially to the origin of the ophthalmic artery. Eighty-four percent of the ophthalmic arteries arose from the supraclinoid segment of the ICA. In the ipsilateral pterional approach, mobilization of the ipsilateral optic nerve was required to see the origin of the ipsilateral ophthalmic artery and the medial aspect of the proximal portion of the supraclinoid segment of the ICA. In the contralateral pterional approach, on the other hand, these areas on the contralateral side could be identified under the optic nerve with minimal or without retraction of the contralateral optic nerve. This was because 71% of the ophthalmic arteries arose from the supero-medial aspect of the ICA, and because there was nothing to intercept the view of the medial aspect of the ICA under the optic nerve. This study supports the usefulness of the contralateral pterional approach to the origin of the ophthalmic artery and the medial aspect of the supraclinoid segment of the ICA. This approach could be useful in certain cases of carotid-ophthalmic aneurysm. The authors' experience with the contralateral pterional approach to carotid-ophthalmic aneurysms is also described. PMID- 4025023 TI - Barbiturates for cerebral aneurysm surgery. A review of preliminary results. AB - Ninety-two cerebral aneurysm cases treated by clipping under moderate hypothermia are reviewed. Twenty-three of these cases received pentobarbitone during surgery in doses sufficient to render the EEG flat. The overall combined mortality and morbidity (complication rate) among 69 non-barbiturate cases was 21.7%. There were significant differences in results between aneurysms in different anatomical locations. The complication rate among eight middle cerebral artery aneurysm cases was 62.5% and among ten internal carotid artery bifurcation cases 40%, while that among nineteen internal carotid artery cases was 16% and among 27 anterior communicating complex cases 7.4%. The overall complication rate among 23 pentobarbitone cases was 17%. There were no complications among eight middle cerebral artery cases; one of two internal carotid bifurcation cases became hemiplegic following occlusion of the middle cerebral artery at is origin. The complication rate among nine internal carotid cases was 22%. No difficulties were experienced regarding haemodynamic stability or cardiac rhythm while using pentobarbitone at normothermia or at 28 degrees C. It is suggested that cerebral aneurysms involving the middle cerebral artery which appear to be most at risk may have the most to gain by the prophylactic use of pentobarbitone during surgery. PMID- 4025025 TI - [Dexamethasone suppression test and unipolar-bipolar classification of depression]. PMID- 4025026 TI - [Use of the dexamethasone suppression test in a prospective study of pseudodementias]. PMID- 4025027 TI - [The epileptic and his family: neurologic and psychological factors of peculiar pathologic dynamics]. PMID- 4025028 TI - [Osgood's semantic differential in neurotics]. PMID- 4025029 TI - [Startle epilepsy: review of the literature and case report]. PMID- 4025031 TI - Chronic treatments in neuropsychiatry. PMID- 4025030 TI - [Differential profile of psychiatric emergencies in a general hospital and a psychiatric hospital]. PMID- 4025032 TI - Chronic and recurrent affective disorders: incidence, course, and influencing factors. PMID- 4025033 TI - Practical problems of lithium maintenance treatment. PMID- 4025034 TI - Response to lithium prophylaxis in schizoaffective psychoses. PMID- 4025035 TI - Approach to chronic and treatment-resistant depressions. PMID- 4025036 TI - Role of diagnosis in resolving issues concerning the treatment of chronic depressive disorders. PMID- 4025037 TI - How many, and which patients with affective disorders need long-term maintenance therapy? PMID- 4025038 TI - Long-acting therapy of schizophrenia. PMID- 4025039 TI - Neuroleptic blood levels and tardive dyskinesia. PMID- 4025040 TI - Extrapyramidal effects of benzamides. PMID- 4025041 TI - Neuroendocrine effects of haloperidol decanoate in patients with chronic schizophrenia. PMID- 4025043 TI - A new model of liposuction cannula. AB - A new design for the suction cannula used in suction curettage is presented. Based on several years' experience in patients from 17 to 63 years of age, the new device allows softer movements intraoperatively, a correct grasp, and excellent suction. PMID- 4025042 TI - Hypothesis of a deficiency of central noradrenergic input in DST nonsuppressor depressed patients. A clinical study with determination of DST and plasma DOPEG: negative results. PMID- 4025044 TI - Adjuvant use of the suction lipectomy cannula for blunt dissection. AB - The blunt-tipped suction lipectomy cannula has proven to be quite effective and is now readily available for dissection of soft tissue spaces. Several clinical examples demonstrating the versatility and utility of this instrument are presented. PMID- 4025045 TI - Treatment of male pattern baldness with one-stage flap. AB - A 1-stage correction of baldness is described, using a vertical preauricular or retroauricular flap, and employing local anesthesia rather than general anesthesia. PMID- 4025046 TI - Method of tying up hair during hair transplantation. AB - We have reported on a simple and secure method of tying up hair during transplantation surgery for alopecia. The implements used were Kocher's forceps and rubber bands which are readily obtainable in the operating theater. PMID- 4025047 TI - Autologous blood transfusion for combined plastic surgeries. AB - Autologous blood transfusion is indicated and helpful for any patient who is entering surgery in whom the surgeon anticipates a large blood loss because of the multiple or combined plastic operations being planned for one surgical sitting. The advantages of autologous over homologous transfusions include avoidance of incompatibility reactions, better volume expansion, and no risk of acquiring diseases. PMID- 4025049 TI - Structure and biochemistry of collagen. AB - The structure and immunochemistry of the interstitial collagens (types I, II, and III), and the structure of basement membrane collagen (type IV) and filamentous collagen (type VI) are described, together with the implications of the different types of collagen. PMID- 4025048 TI - Rhomboid transposition flaps. AB - The limitations of the Limberg, Dufourmentel, and Webster flaps are analyzed. The use of multiple rhomboidal transposition flaps to close rhomboidal surgical defects is illustrated. PMID- 4025050 TI - Collagen injections: two years' experience. AB - A total of 165 patients with varying indications have been treated with Zyderm Collagen Implant. Among these patients, only 4 allergic reactions were found: 3 local and 1 general. Results obtained depend on the type of lesion treated; it is suggested that the treatment of rhytids provides the best indication for collagen implant. PMID- 4025051 TI - Experience with collagen injection for the correction of contour deficiencies. AB - The author reports on the successful use of collagen injections after surgery for the correction of inter-superciliary lines and missing tissue lesions after rhinoplasty. Less successful results were obtained with naso-labial lines or lesions of excess tissue after rhinoplasty. Caution is advised in the use of collagen injections for congenital lesions. PMID- 4025052 TI - Prevention of postoperative facial edema with steroids after facial surgery. AB - A one-bolus (dose) of 1 g of methylprednisolone was administered intravenously to patients undergoing facial surgery or craniofacial surgery, before the termination of the operative procedure. The degree of facial edema noted was reduced, and when it occurred, it was mild and of shorter duration. These observations were made on the experimental design first, and later in the clinical setting. No adverse effects were noted, and patients given this treatment required less pain medication in the immediate postoperative period. The mechanism of action of the steroids is multifactorial, related to decrease in the accumulation of fluid at the capillary level, and reduction of flow at the venoarterial sphincters. The use of steroids is safe when used with caution in selected patients, and by experienced surgeons. PMID- 4025053 TI - Polyurethane-covered silicone gel mammary prosthesis for successful breast reconstruction. AB - A polyurethane-covered silicone gel implant has been used by the author in 150 breast reconstructions and augmentations in the past 9 years. The results have been most gratifying with regard to breast softness, breast compressibility, and esthetics. Only 4 patients have developed a unilateral capsule contracture and firm breast. The reasons are postulated for these satisfying results. Complications have been few and very minor. PMID- 4025054 TI - Complications with homologous fat grafts in breast augmentation surgery. AB - The most common complications in breast augmentation surgery with homologous fat grafts obtained from fresh cadavers are presented, showing subsequent surgical procedures to reconstruct the breasts of such patients through use of silicone prostheses and muscle flaps from the latissimus dorsi. PMID- 4025055 TI - An unusual case of gigantomasty. AB - The authors report an unusual case of gigantomasty, of such proportions that it is believed to be the most striking published case, when the ratio of breast weight/body weight is taken into account (24%). The outstanding breast volume and the aggressive and pronounced growth potential of the breast tissue presented unusual problems which required special solutions. The case is presented from its beginning, when the patient was 12 years old up to the completion of treatment with the patient at adult age. PMID- 4025056 TI - Reduction suction mammoplasty and suction lipectomy as an adjunct to breast surgery. AB - Suction lipectomy has become an accepted procedure and its full use is still being elucidated. The author herein describes the use of suction lipectomy as an adjunct in refining the results of established surgical procedures on the breast. The authors also explain the use of suction lipectomy in doing "suction reduction" mammoplasty. The advantages of the use of suction lipectomy as an adjunct to breast surgery and for reduction mammoplasty are explained. PMID- 4025057 TI - [Studies on congenital constitution by HLA antigens relating to lattice degeneration and rhegmatogenous retinal detachment]. PMID- 4025058 TI - [Enhancement of evoked potentials by saccadic eye movement--effect of attentional buzzer]. PMID- 4025059 TI - [Effects of panretinal photocoagulation on posterior fundus in diabetic retinopathy. Analysis of local macular electroretinogram and visual evoked response]. PMID- 4025060 TI - [A new analysis of the Farnsworth-Munsell 100-hue test]. PMID- 4025061 TI - [A new apparatus for automatic counting of aqueous floaters]. PMID- 4025062 TI - [Light and electron microscopic study on the iris stromal vessels in capsular glaucoma]. PMID- 4025063 TI - [Aging changes in the peripheral cornea]. PMID- 4025064 TI - [Studies of stereoptic VEPs with static random-dot stereograms--stimulus parameters]. PMID- 4025065 TI - [Studies on peak latency and phase of pattern VEPs by inverse Fourier transform]. PMID- 4025066 TI - [Study on development of collateral circulation following anterior uveal ischemia in rabbit eyes. 1. Occlusion of the long posterior ciliary arteries]. PMID- 4025067 TI - [Chemotaxis of polymorphonuclear leucocytes in the crystalline lens. 2. Pathological experiment]. PMID- 4025068 TI - [Analysis of aqueous humor proteins]. PMID- 4025069 TI - [Functional disorder of retinal pigment epithelium after cataract extraction]. PMID- 4025070 TI - [Basilar impression combined with Arnold-Chiari malformation and syringobulbia- M.R.I. (magnetic resonance image, N.M.R.) diagnosis]. PMID- 4025071 TI - [Polygenic analysis of keratoconus]. PMID- 4025072 TI - [Studies on the causative factor of the Descemet's membrane ruptures at birth on the development of form vision deprivation amblyopia]. PMID- 4025073 TI - [Investigation of the vitreo-retino-ciliary barrier by vitreous fluorophotometry. I. Evaluation of age differences in normal adults]. PMID- 4025074 TI - [The effect of body position on intraocular pressure in normal and glaucomatous eyes--a comparative study with pneumatonograph]. PMID- 4025075 TI - [Langerhans cells in vernal conjunctivitis]. PMID- 4025076 TI - [Ophthalmic care of very low birthweight infants. Report 2. Transient cataracts in very low birthweight infants]. PMID- 4025078 TI - [Renal arterial embolization for renal cell carcinoma]. AB - Renal arterial embolization is often used in the treatment of patients with renal cell carcinoma, either preoperatively to facilitate nephrectomy or as palliative therapy in advanced cases. Eighteen patients (18/58; 31%) underwent renal arterial embolization in our department since 1979, initial 10 cases with Gelfoam and steel coil (group G) and recent 8 cases with absolute ethanol (group A). Clinical studies of daily changes of symptoms and blood chemistry in both groups after embolization were compared and the results were as follows: Severe flank pain was noted immediately after embolization but thereafter well controlled without analgesics in group A. The patients in group G experienced no pain during the procedure of embolization but have had moderate flank pain of two or three days' duration with nausea and/or vomiting and required surgical procedure within a few days after embolization. Post embolization fever in group A was described as higher than that in group G significantly. Leukocytosis was noted to be persistent for up to seven days and blood chemistry showed transient marked elevations of GOT, GPT and LDH immediately after the procedure without significant value in both groups. Embolization to advanced tumor with many parasitic vessels or massive local invasion may not always be available for remaining of viable-appearing tumor cells in venous lumen, as if palliative treatment. Absolute ethanol may be more useful as the embolizing substance than Gelfoam and steel coil by reason of producing wide severe infarction of diseased kidney. Broad marked infarction due to renal arterial embolization may make pathological diagnosis difficult. Immunological effects of renal arterial embolization were not observed in short term patients survival.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4025077 TI - [The treatment of renal cell carcinoma with recombinant human leukocyte interferon]. AB - Recombinant human leukocyte (alpha) interferon was administered i.m. at the initial dose of 3 X 10(6) U/day to 27 patients with measurable metastatic renal cell carcinoma during the past 2 years. The results of 22 of these patients were evaluable. Three patients (13.6%) showed partial response; 3 patients (13.6%), minor response; 7 patients (31.8%), no change; and 9 patients (40.9%), progressive disease. Major toxicity consisted of fever (55.5%), anorexia (44.4%), malaise (22.2%), elevation of GOT/GPT (48.1%), leukopenia (44.4%) and thrombocytopenia (29.6%). When the 3 patients who showed stabilization (S) and the 2 patients who showed mixed effects (ME) among the 7 patients who showed no change are classified into the responded group, half the patients had some response to interferon. Characteristics of these responders (PR + MR + ME + S) were good performance status, relatively longer disease-free interval, metastases limited to the lungs or metastasis to lungs and one other organ excluding the liver, and frequency of interferon-induced thrombocytopenia. Interferon administration is still being continued to 4 patients on an outpatient basis, 5 patients are hospitalized and 13 patients have died. In conclusion, patients with pulmonary metastases seem to be the best responding group for interferon treatment in renal cell carcinoma and further trials, especially combined regimens with chemotherapy and/or other kinds of interferon should be tested. PMID- 4025079 TI - [The determination of oxalate in the urine by a new enzymatic method using oxalate oxidase]. AB - Oxalate is one of the most important constituents in urine of urinary stone. But the determination of oxalate in urine has not been performed as a routine laboratory examination because of difficulty or inaccuracy in measuring oxalate in urine. We tried to measure oxalate in urine by the newly developed enzymic method with oxalate oxidase. This method is not only simple but also accurate enough. The reproducibility S.D./mean was 2.3-9.0%, the recovery rate was 95.2 +/ 4.0% (mean +/- S.D.) With this method, the normal range of urine oxalate in 24 hours was determined to be 11.8 mg-39.4 mg, the upper limit was 40 mg. By taking the regular diet which contains 500 mg of calcium and 1,000 mg of phosphorus a day, the excretion of oxalate in urine was significantly decreased in the stone formers. This suggests that the influence of the diet upon the excretion of oxalate in urine for 24 hours is important especially in stone formers. PMID- 4025080 TI - [The effectiveness of a combination of trimethoprim plus rifampicin and local injection of antibiotics into the prostate in chronic bacterial prostatitis]. AB - Seventy out-patients suffering from chronic bacterial prostatitis were treated with a combination of trimethoprim plus rifampicin or trimethoprim alone. A combination of 300 mg. rifampicin plus 160 mg. trimethoprim (rifaprim) was used. Forty-four patients were administered rifaprim at doses of 920 mg. (twice a day) for two months. Twenty-six patients were administered trimethoprim at doses of 320 mg. (twice a day) for two months. Cultures of the expressed prostatic secretions (EPS) yielded gram-positive bacteria in 61 patients and gram-negative bacteria in 9. In rifaprim group, clinical responses were excellent in 9 cases, moderate in 23 cases and poor in 12 cases. The efficacy rate was 73%. In trimethoprim group, excellent in 1 case, moderate in 14 cases and poor in 11 cases. The efficacy rate was 60%. Seven patients of chronic bacterial prostatitis were treated by local injection of tobramycin into the prostate. The antibiotic level in the prostatic fluid twenty-four hours after injection was very high. The pain and discomfort experienced by the patients during injection into the prostate were minimal. Local necrosis was not found after histologic or electron microscopic studies of biopsied prostatic specimen after the injection. Results show that this simple method should be valuable in the treatment of the refractory group of chronic bacterial prostatitis. PMID- 4025082 TI - [Horseshoe kidney in an infant associated with ureteropelvic junction and ureterovesical junction obstructions]. AB - A 4-month old baby was seen in August, 1982 because of abdominal distension. The findings of the physical examination were normal except for a man's fist sized mass in the left upper abdomen. IVP revealed left nonvisualizing kidney. CT scans revealed a large mass in the left abdomen with low density contents and renal scintigraphy revealed a horseshoe kidney. The tentative diagnosis was horseshoe kidney associated with hydronephrosis due to ureteropelvic junction obstruction. Left pyeloplasty was performed in September 1982 and postoperative X-ray examinations revealed left ureterovesical junction obstruction. Left ureteroneocystostomy was performed in October, 1982 and postoperative course was uneventful. Horseshoe kidney in infants is rare in the Japanese literature and our case is quite unique in that horseshoe kidney is associated with ureteropelvic junction and ureterovesical junction obstruction. PMID- 4025081 TI - [Tuberculosis of the contralateral adrenal gland: a case report]. AB - Unilateral adrenal tuberculosis is a very rare disease. A 66-year-old woman presented with epigastric discomfort and general fatigue. Abdominal CT scan revealed a homogeneous mass shadow in the right adrenal region. Findings of physical examination were normal except that the patient was obese. Hormonal data were in normal range. Adrenal scintiscanning demonstrated no RI uptake in the right adrenal gland. Right adrenalectomy was performed under the diagnosis of nonfunctioning tumor of the right adrenal gland. Histopathological examination, however, revealed typical tuberculosis with Langhans' type of giant cells and infiltrated lymphocytes. Of 322, 148 autopsies performed during the twelve years between 1970 and 1981 in Japan, 228 cases of adrenal tuberculosis were recognized. Furthermore, only 18 cases had tuberculous regions in the adrenal gland alone. PMID- 4025083 TI - [Renal cell carcinoma, primary lesion which was not easily identified: report of two cases]. AB - We report two cases of renal cell carcinoma, primary lesions of which were not diagnosed at an early stage. The first case was a 58-year-old woman, who had nephrectomy due to staghorn calculus of left kidney. Fifteen months later, she died of metastatic cancer whose origin was unknown until the left kidney was re examined. It was sarcomatoid renal cell carcinoma. The second case was 43-year old woman, who had amputation of right index finger due to metastatic tumor. Renal cell carcinoma was highly suspected, but no tumor could be found in her kidneys although various urological examinations were performed. Two years later, abdominal CT scan showed a space-occupying lesion (SOL) of left kidney. She had left nephrectomy, and the origin was finally identified. PMID- 4025084 TI - [A case of bilateral ureteral triplication]. AB - Ureteral triplication is a rare congenital anomaly of the urinary tract, although ureteral duplication is rather common. Bilateral ureteral triplications are even rare anomalies. A five-year-old girl with a history of urinary tract infection and episodes of fever and lower abdominal pain was admitted to our hospital for further examination of microscopic hematuria. An excretory urogram (IVP) revealed bilateral 3 pelves and ureters, and cystoscopic examination showed 2 ureteral orifices on each side. Both sides of bilateral ureteral triplications in our case belonged to type B of Smith's classification. Ureteral triplication was first reported by Wrany in 1870. Since then 84 cases have been reported and among them 3 cases had bilateral ureteral triplications. In this article, the classification and the development of ureteral triplication are reviewed briefly. PMID- 4025085 TI - [Blind-ending bifid ureter: a case report]. AB - This is a report on a case of blind-ending ureter. The patient was a 56-year-old female who had complained of a pain in the left flank. There was no urinary tract infection. Excretory urography revealed a left blind-ending bifid ureter. It was resected and the removed specimen was about 8 cm in length. Histologically, it had all layers of the ureteral structure, but no renal tissue was found. The post operative course was uneventful. We collected 55 cases of blind-ending bifid ureters reported in Japan including our own and discussed the difference between blind-ending bifid ureter and ureteral diverticulum. PMID- 4025086 TI - [A case of recurrent yolk sac tumor of the testis in childhood: bulky retroperitoneal metastatic tumors cured by tumor resection and chemotherapy]. AB - We carried out only high orchiectomy for a 1-year and 7-month-old boy with stage 1 yolk sac tumor of the testis, after 13-months a bulky retroperitoneal metastatic tumor was found. Following chemotherapy with CDDP, ACD, VBL, PLM and CTX two times after tumor resection, elevated serum AFP was normalized. He has been in continuous complete remission with no evidence of disease for 3 years and 2 months. Combination chemotherapy with CDDP has a dramatic effect on the yolk sac tumor of infantile testis. We believe that "watchful waiting" after high orchiectomy alone is the best modality for all cases of stage 1 yolk sac tumor of the infantile testis. PMID- 4025087 TI - [A case of epidermoid cyst of the testis]. AB - A 32-year-old business man was admitted with the chief complaint of a right testicular mass without pain. Laboratory findings including serum AFP, HCG, and beta-HCG were within normal limits. Right high orchiectomy was performed under the diagnosis of testicular tumor. The cyst was located at the middle of the testis and was 3.5 X 3.0 X 2.0 cm in size. The cut surface of the tumor revealed a fibrous capsule with a keratin mass in it. Histological diagnosis was a benign epidermoid cyst. This case seems to be the 56th case of epidermoid cyst of the testis reported in the Japanese literature. PMID- 4025089 TI - Health policy in 1985 and beyond. PMID- 4025088 TI - [Studies on antibiotics distribution in the post-operative cavity]. AB - In 17 post-operative patients, serum and operation cavity exudate levels after 2 g administration of various cephems (CZX, LMOX, CTX, and CPZ) by one hour drip infusion were evaluated. Drug concentration in exudate (actual levels) was corrected by using an equation for the purpose of excluding blood contamination. After 2 hours from the start of infusion, theoretical levels generally were similar to actual levels. CZX: Peak exudate level was 38.9 micrograms/ml at 4 hours. Maximum exudate level/maximum serum level (E/S) was 0.31. LMOX: Peak in exudate was 41.4 micrograms/ml at 4 hours. E/S was 0.59. CTX: Exudate peak level was 30.8 micrograms/ml at 2 hours, and E/S was 0.53. CPZ: Peak level in exudate was 74.0 micrograms/ml at 4 hours. E/S was 0.36. Generally, peaks occurred at 4 hours (3 hours later than serum peaks), and their range was between 30 and 80 micrograms/ml. At 8 hours, drug levels in exudate were 10 approximately 60 micrograms/ml, and they were higher than the corresponding serum level at that time. PMID- 4025090 TI - Dental implications of fluorides in medical practice. PMID- 4025091 TI - Magnetic resonance imaging; early experience with high field strength superconducting magnet. PMID- 4025092 TI - Caring for Alabama's secondary school athletes. PMID- 4025093 TI - A framework for considering educational and non-educational influences on the attainments of deaf persons. PMID- 4025094 TI - Mothers learning simultaneous communication: the dimensions of the task. PMID- 4025095 TI - A revised form of the Tennessee Self-Concept Scale for use with deaf and hard of hearing persons. PMID- 4025096 TI - A comparison of levels of tolerance for ambiguity in deaf and hearing school children. PMID- 4025097 TI - The effects of context on deaf students' comprehension of difficult sentences. PMID- 4025098 TI - A functional classification system for the deaf-blind. PMID- 4025099 TI - Conceptual sign language as a bridge between English and Spanish. PMID- 4025100 TI - Spatial-relationship deficits in deaf children: the effect on communication and classroom performance. PMID- 4025101 TI - Elder abuse. AB - Family physicians need to know the predisposing factors for elder abuse, which may be as common as child abuse and spouse abuse. Victims and abusers often seek assistance through medical services. Neglect is probably the most common form of elder abuse, followed by emotional or verbal abuse and abandonment. Physical abuse is relatively rare. Intervention strategies should include not only the victim but also the abuser. PMID- 4025102 TI - Hyperosmolar nonketotic diabetic coma. AB - Hyperosmolar nonketotic coma occurs most frequently in the elderly patient with underlying renal impairment. It often has an insidious onset, and may be precipitated by an identifiable illness, medication or procedure. Various neurologic manifestations may occur and obscure the diagnosis. Rapid recognition and appropriate treatment can greatly reduce the high mortality rate. PMID- 4025103 TI - Lower cervical spine trauma. PMID- 4025105 TI - Treatment protocols for PID. PMID- 4025104 TI - Managing patients on oral contraceptives. PMID- 4025106 TI - Recurrent aphthous stomatitis. AB - Aphthous ulcers are of unknown etiology; both genetic and immunologic origins have been proposed. Lesions are painful, tend to recur and may last up to six weeks. Recurrent aphthous stomatitis must be differentiated from herpesvirus infections and herpangina. No treatment has been uniformly successful, but levamisole shows promise. PMID- 4025107 TI - Coronary artery spasm induced in miniature swine: angiographic evidence and relation to coronary atherosclerosis. AB - In a swine model of coronary artery spasm, the pathogenetic role of coronary atherosclerosis was examined. Following endothelial balloon denudation of the left circumflex coronary artery (LCX), male miniature swine were fed a laboratory chow diet containing 2% cholesterol. Although there was no difference in the extent of coronary vasoconstrictive response to histamine, serotonin, and ergonovine between the left anterior descending coronary artery (LAD) and the LCX before the denudation, a constrictive response was significantly augmented along the denuded portion of the LCX 1 and 3 months after the denudation. Augmented vasoconstrictive responses to phenylephrine were never evidenced. Histamine was the most potent vasoactive agent, and coronary artery spasm was provoked repeatedly by intracoronary or intravenous administration of histamine in the presence or absence of cimetidine. The spasm was provoked only in the denuded portion of the LCX, the same area which was angiographically normal before the occurrence of the spasm. Histologically, atherosclerotic changes were predominant along the denuded portion of the LCX. Topologic correlation was suggested between the site of the spasm and the site of coronary atherosclerosis. It is concluded that in this swine model of coronary artery spasm, atherosclerotic changes may be an important causative factor, in terms of an activation of multiple receptor operated calcium channels in the coronary artery. PMID- 4025108 TI - Left ventricular diastolic filling in patients with coronary artery disease and normal left ventricular function. AB - Abnormal left ventricular diastolic filling (DF) has been noted in coronary disease (CD) patients with normal left ventricular function (NLVF). Inclusion of patients with regional wall disease, hypertension, and left ventricular hypertrophy may be responsible for abnormal DF. We evaluated left ventricular DF curves derived from gated blood pool scans in 21 normals (group 1), in 38 CD patients with NLVF specifically defined (group 2), and in 28 CD patients with ejection fractions greater than 50% and regional disease (group 3). The peak filling rate (PFR), mean filling rate (MFR), the percentage of stroke volume filled at one third of diastole (%SV-1/3 DT) and at the end of the rapid filling period (%SV-RFP) were determined. Groups 1 and 2 had similar DF parameters. Group 2 patients with 75% obstructive left anterior descending disease (LAD) had a reduced %SV-RFP and PFR (2.56 +/- 0.56 end-diastolic volumes/sec [EDV/S]) as compared to normals (3.11 +/- 0.65 EDV/S, p less than 0.01). Group 3 patients had a reduced PFR (2.14 +/- 0.53 EDV/S, p less than 0.001), MFR, %SV-1/3 DT, and %SV RFP. DF in CD patients with NLVF was similar to normals in a select group of patients but was abnormal in patients with regional disease and greater than 75% LAD disease with NLVF. PMID- 4025109 TI - Left ventricular filling is usually normal in uncomplicated coronary disease. AB - Abnormalities in left ventricular filling have been described as an early finding in coronary artery disease (CAD) and more recently, in hypertension (HTN). The present study was undertaken to compare the prevalence and pattern of diastolic dysfunction in these two entities. Three groups of patients were studied: 10 normal volunteers (NLS), 39 HTN patients, and 30 CAD patients. The CAD patients were divided into two subgroups--one with normal ejection fraction (mean 0.60 +/- 0.06) and the second with either a depressed ejection fraction (EF) or a history of HTN (mean EF 0.44 +/- 0.15). The diastolic indices examined were peak filling rate (PFR, in end-diastolic volume [EDV]/sec), time to peak filling rate (TPFR, in msec), and first-third filling fraction (FF 1/3, in sec-1). The PFR in CAD and HTN was significantly reduced (1.86 +/- 0.63 and 2.29 +/- 0.49 vs 2.70 +/- 0.35 EDV/sec in NLS, p less than 0.025 and p less than 0.001, respectively), with the CAD group also being significantly lower than the HTN group (p less than 0.005). TPFR was prolonged in HTN, but not in CAD. FF 1/3 was reduced in both HTN and CAD (0.38 +/- 0.11 and 0.50 +/- 0.14 vs 0.61 +/- 0.06 sec-1 in NLS, p less than 0.001 and p less than 0.025, respectively), but it was significantly lower in HTN than in CAD (p less than 0.001). However, when the subgroup of CAD patients with normal global systolic function was examined separately, diastolic indices were only slightly depressed. More importantly, only one, two, and five patients had PFR, TPFR, and FF 1/3, respectively, which were below the normal values of our laboratory. PMID- 4025110 TI - Drinking and coronary heart disease: the Albany Study. AB - The relation of alcohol consumption to coronary heart disease (CHD) was examined in a cohort of 1910 employed men aged 38 to 55 years enrolled in the Albany Study, a prospective investigation of factors related to cardiovascular disease. Two follow-up periods were examined, one between 1953-54 and 1971-72, the other after 1971-72. In the initial period, there was no clear evidence of a relation between the rate of alcohol consumption and CHD incidence. In the later period, men whose monthly consumption was 60 ounces or more had a lower than average CHD incidence rate. A negative relationship with drinking held for all manifestations of CHD. Other CHD risk factors were examined, special attention being given to cigarette smoking and HDL-cholesterol. The fact that drinking is a matter of choice may introduce some confounding factors. The absence of a relation between drinking and CHD risk in the earlier follow-up suggests the need for caution in interpreting the results. PMID- 4025111 TI - The effect of bretylium and clofilium on dispersion of refractoriness and vulnerability to ventricular fibrillation in the ischemic feline heart. AB - Bretylium has been shown to have a pronounced antifibrillatory effect. The purpose of this study was to examine the effects of bretylium on changes in vulnerability to ventricular fibrillation (VF) and refractoriness which occur during acute myocardial infarction. Right ventricular VF thresholds and effective refractory periods (ERP) at six left ventricular sites were measured before and serially after left anterior descending coronary occlusion in chloralose anesthetized cats. In eight untreated animals, there was a decrease in VF thresholds of 73% (p less than 0.01) immediately after occlusion and dispersion of refractoriness (DR) (maximum difference in ERP between normal and ischemic left ventricular sites) increased from 18 +/- 4 to 50 +/- 6 msec (p less than 0.01). Five of eight animals manifested spontaneous VF within the first minutes of occlusion but none had nonsustained VF. Pretreatment with bretylium (10 to 20 mg/kg intravenously) increased resting ERP from 181 +/- 9 to 201 +/- 9 msec (p less than 0.05) and VF threshold from 32 +/- 5 to 85 +/- 7 mA (p less than 0.001). Bretylium also prevented spontaneous VF in all eight animals and abolished occlusion-related changes in VF and DR. Fourteen animals were similarly studied using clofilium, a bretylium congener which is devoid of sympatholytic effect (no effect on blood pressure response to bilateral carotid artery occlusion). Clofilium increased resting ERP and VF thresholds at both low (0.5 mg/kg intravenously) and high doses (5 mg/kg intravenously). High-but not low dose clofilium blunted the fall in VF threshold after coronary occlusion. In addition, DR correlated with VF threshold changes at both doses.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4025112 TI - Amiodarone and sustained ventricular arrhythmias: statistical evidence of drug effectiveness. AB - Previous studies have shown that amiodarone prevents sustained ventricular arrhythmias in 77% to 93% of patients. To date, a study using statistical analysis to verify the drug's effectiveness has not been reported. Amiodarone was given to 17 patients with drug refractory sustained ventricular arrhythmias. All patients had serious underlying heart disease including coronary artery disease (15 patients) or cardiomyopathy (two patients). Ten patients had angiographic evidence of a left ventricular aneurysm. All patients had left ventricular dysfunction. The mean left ventricular ejection fraction was 33%. In the 5.5 +/- 8.3 months prior to amiodarone, these 17 patients had documented sustained ventricular arrhythmias requiring countershock (41 episodes), overdrive pacing (four episodes), or intravenous drugs (three episodes). Amiodarone was given as a loading dose (1 gm/day for 10 days) and a maintenance dose (200 to 600 mg/day). During a follow-up period of 8.9 +/- 5.7 months, only eight episodes occurred requiring countershock (5) or overdrive pacing (2); one patient died suddenly. A statistical test constructed for this problem showed a significant (p greater than 0.001) reduced risk of experiencing a sustained ventricular arrhythmia after amiodarone. This statistical model confirms previous studies showing that amiodarone prevents sustained ventricular arrhythmias and prevents sudden cardiac death. PMID- 4025113 TI - Cardiac function in patients on chronic amiodarone therapy. AB - Antiarrhythmic agents may depress cardiac contractility and worsen heart failure. Few data are available describing the chronic effects of amiodarone on myocardial function. To assess the effects of amiodarone on cardiac function, we studied 41 consecutive patients with first-pass or equilibrium radionuclide angiography prior to and 3 months after drug therapy was initiated. The mean heart rate, systolic blood pressure (BP), and diastolic BP were not significantly altered by treatment. The mean ejection fraction was 36% +/- 19 (mean +/- 1 SD) at the time of drug initiation and 36% +/- 17 3 months later (p less than 0.05). Nineteen patients had an ejection fraction greater than 30% and 16 had an ejection fraction less than 30%. The mean change in ejection fraction for these two subgroups showed no statistically significant difference, although a decrease in EF greater than 10% was seen in three patients (symptomatic in two), necessitating an increase in diuretic dose. No correlation between amiodarone dose and change in ejection fraction (r = -0.12, p greater than 0.05) was noted. There was no correlation between baseline ejection fraction and change in ejection fraction over this 3-month period (r = -0.36, p greater than 0.05). In summary, amiodarone does not depress left ventricular function and as a result can be used safely in patients with mild to moderate impairment of left ventricular function. In patients with stable left ventricular function, serial tests of left ventricular function may not be necessary. PMID- 4025114 TI - Mitral-septal angle: a new two-dimensional echocardiographic index of left ventricular performance. AB - The diagnostic value of a new two-dimensional echocardiographic measurement, the mitral septal angle, was evaluated as an index of left ventricular (LV) function in 122 patients. Their mean age was 56.5 years and the majority (80%) suffered from coronary artery disease, 46 with an acute myocardial infarction. Mitral septal angle was easily and reproducibly measured. An ejection fraction (EF) of greater than or equal to 50% and an angle less than or equal to 30 degrees were used as normal cut-off values. A strong negative correlation was found between the angle and radionuclide EF (-0.821) and angiographic EF (-0.82) in patients without acute myocardial infarction. For patients with acute myocardial infarction, the correlation was -0.722. For the entire group, the correlation coefficient was -0.742. In patients without acute infarction, the sensitivity, specificity, and predictive accuracy of the mitral septal angle were 92%, 86%, and 89%, respectively. In acute infarction, sensitivity dropped to 70% without change in specificity (89%). We conclude that mitral septal angle is a simple index of LV function which relates well to EF, particularly in patients with chronic heart disease. PMID- 4025115 TI - Potentiation by calcium channel blockade of hypoxic myocardial depression in the neonate. AB - The objectives of this study were to examine the independent and combined effects of beta blockade (practolol) and calcium channel blockade (verapamil) on cardiac responses to hypoxia in the neonate. Lambs were anaesthetized with pentobarbital (20 mg/kg) and were prepared for measurements of left ventricular (LV) performance under controlled hemodynamic conditions. Force generation was assessed from curves relating LV systolic pressure (SP) to end-diastolic pressure (LVEDP) over a broad range of afterloading. Velocity was determined from simultaneous measurements of LV dP/dtmax. Values obtained at LVEDP 10 cm H2O were used to compare interventions. Practolol (P) caused no significant reduction in SP10, but dP/dt10 fell from 51 to 37 (X 10(2] mm Hg/sec (p less than 0.05). Verapamil (V), 2 micrograms/min/kg, reduced measures of contractility (p less than 0.01). Doubling the dose of V further reduced SP10 to 79% of control. Hypoxemia (PaO2, 32 torr) increased SP10 from 172 to 192 mm Hg, and dP/dt10 from 51 to 85 (X 10(2] mm Hg/s (p less than 0.001). After P, the same degree of hypoxia elicited no changes in LV function. During infusion of V (4 micrograms/min/kg), hypoxia reduced SP10 from 138 to 122 mm Hg (p less than 0.01) and dP/dt10 from 29 to 24 (X 10(2] mm Hg/sec (p less than 0.05). It is concluded that in the absence of adrenergic support, hypoxia significantly depresses both force and velocity parameters of contractility in hearts with calcium channel blockade. PMID- 4025116 TI - Left ventricular performance in septic shock: reversible segmental and global abnormalities. AB - Left ventricular dysfunction has been implicated in the pathogenesis of septic shock, but little is known about its natural history, cause, and prognostic significance. Left ventricular performance was assessed by serial radionuclide and hemodynamic studies in 35 patients with culture-proven septic shock. The mean age (+/- S.D.) of the group was 64 +/- 18 years; 16 of the subjects were women, and 15 had antecedent heart disease. On the first study, the left ventricular stroke work index was depressed in 33 (94%) patients, and nineteen (54%) had a left ventricular ejection fraction less than 0.48. Twenty-two (63%) of the patients had segmental and four had generalized wall motion abnormalities. Conventional hemodynamic parameters were of no value in predicting the patients who had a depressed left ventricular ejection fraction or segmental abnormalities. Patients with underlying heart disease had a much higher frequency (87%) of segmental dysfunction than those without underlying heart disease (45%; p = 0.016), but no differences were noted in the left ventricular ejection fraction or left ventricular stroke work index of these two groups. Segmental abnormalities and low ejection fractions were seen more often in patients with a large left ventricular end-diastolic volume index. Only five subjects had a systemic vascular resistance index greater than 2580 dynes X sec X cm-5 per m2, and the correlation between systemic vascular resistance index and left ventricular ejection fraction was poor. No difference was found in the mean coronary perfusion pressure of those with segmental abnormalities and those with normal wall motion.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4025117 TI - Hemodynamic effects of verapamil in left ventricular valvular volume overload. AB - The hemodynamic consequences of aortic and mitral insufficiency may be influenced by the high systemic vascular resistance often seen in these patients. Since the calcium antagonists have been shown to reduce systemic vascular resistance, we evaluated the effects of intravenous verapamil in 23 patients. In 11 patients with aortic insufficiency, verapamil resulted in a 20% increase in cardiac index (p less than 0.001), 18% increase in forward stroke volume index (p less than 0.001), and a 24% decrease in regurgitant fraction (p less than 0.005). In the 12 patients with mitral insufficiency, verapamil resulted in a 19% increase in both cardiac index (p = 0.004), and forward stroke volume index (p less than 0.001), while there was a 19% decrease in regurgitant fraction (p less than 0.02). Left ventricular end-systolic stress decreased significantly in both groups as did end diastolic stress in the mitral insufficiency group. There was no significant change in several measures of contractile performance, though the end-systolic stress-to-volume index ratio fell significantly (p less than 0.04) in the mitral insufficiency group. Our findings suggest that the vasodilatory effects of intravenous verapamil predominate over the negative inotropic effects in patients with aortic and mitral insufficiency. Verapamil may be of use in patients intolerant to other vasodilators, patients with concomitant ischemic heart disease, or those with supraventricular arrhythmias. PMID- 4025118 TI - Analysis of the efficacy of the new cardiotonic agent TA-064. AB - TA-064 is a new cardiotonic agent which is also effective orally, according to investigations conducted in Japan. We analyzed computer-assisted alterations of pressure-volume relationships serially and of indirect myocardial oxygen consumption (MVO2) estimations on line during TA-064 influence in 16 patients with congestive cardiomyopathy: left ventricular function was moderately decreased in seven patients (group A) and drastically decreased in nine (group B). Results showed that TA-064, 8 micrograms/kg/min intravenously, exerted positive inotropic effects in both groups and induced mean maximal delta percentage changes at about 5 minutes of infusion as follows: left ventricular stroke work index +65% and +47%; dP/dtmax +61% and 59%; left ventricular efficiency +62% and 53%; MVO2 +31% and +11% (p less than 0.05). TA-064, 20 mg by mouth induced serum levels (group A = 23.8 +/- 12ng/ml and group B = 26.4 +/- 20 ng/ml) corresponding to the effects with dosages of 1 to 2 ng/kg/min intravenously (p greater than 0.05), thus implying that significant changes in left ventricular function require higher oral dosages. We conclude that TA-064 improves left ventricular function, primarily via a contractility increase, also in group B patients without toxic side effects. On-line indirect MVO2 assessment and analysis of serial pressure-volume relationships helped to provide a more complex definition of the mechanism and efficiency of the cardiotonic agent under study. PMID- 4025119 TI - Electrocardiographic evidence suggestive of myocardial infarction without significant organic heart disease. AB - One hundred nineteen catheterized patients had ECG evidence of myocardial infarction in the absence of significant narrowing of coronary arteries or localized contractile abnormalities of the left ventricle. Eighty-seven had organic heart disease, but 32 had no demonstrable abnormality. ECG alterations in the latter group were almost equally divided between those in lead aVF and in the right precordial leads. Although certain depolarization defects are highly suggestive of myocardial infarction, similar changes may rarely be seen in normal people. PMID- 4025120 TI - Development and evolution of electrocardiographic Minnesota Q-QS codes in patients with acute myocardial infarction. AB - The development of ECG Minnesota Q-QS codes and their subsequent evolution were studied in the first 692 subjects to enter the POSCH program who had had one MI. The mean interval from MI to entry into the study was 2.2 years. Sixty-three percent of the subjects developed the most significant code with the infarction. By the time the subjects entered the study, the codes had commonly regressed to a lower level, disappearing altogether in 34%. The likelihood of complete regression varied inversely with the significance of the code. There was no significant difference between the groups with disappearance and with retention of a Q-QS code as to time since MI, the extent of coronary arterial disease, or the age or sex of the subject. In about half of the subjects the original code did not change with time and in 21% to 44% the code increased to one of a higher level of significance. PMID- 4025121 TI - A logistic regression analysis of multiple noninvasive tests for the prediction of the presence and extent of coronary artery disease in men. AB - The incremental diagnostic yield of clinical data, exercise ECG, stress thallium scintigraphy, and cardiac fluoroscopy to predict coronary and multivessel disease was assessed in 171 symptomatic men by means of multiple logistic regression analyses. When clinical variables alone were analyzed, chest pain type and age were predictive of coronary disease, whereas chest pain type, age, a family history of premature coronary disease before age 55 years, and abnormal ST-T wave changes on the rest ECG were predictive of multivessel disease. The percentage of patients correctly classified by cardiac fluoroscopy (presence or absence of coronary artery calcification), exercise ECG, and thallium scintigraphy was 9%, 25%, and 50%, respectively, greater than for clinical variables, when the presence or absence of coronary disease was the outcome, and 13%, 25%, and 29%, respectively, when multivessel disease was studied; 5% of patients were misclassified. When the 37 clinical and noninvasive test variables were analyzed jointly, the most significant variable predictive of coronary disease was an abnormal thallium scan and for multivessel disease, the amount of exercise performed. The data from this study provide a quantitative model and confirm previous reports that optimal diagnostic efficacy is obtained when noninvasive tests are ordered sequentially. In symptomatic men, cardiac fluoroscopy is a relatively ineffective test when compared to exercise ECG and thallium scintigraphy. PMID- 4025122 TI - The value of electrophysiologic studies in syncope of undetermined origin: report of 150 cases. AB - A prospective study examined the diagnostic yield and therapeutic efficacy of electrophysiologic studies in patients with SUO. We defined SUO as those syncopal or near-syncopal events remaining unexplained after a standardized, noninvasive evaluation that included a history, physical examination, routine laboratory screening, EEG, nuclear brain scan or CAT scan, 12-lead ECG, chest x-ray, orthostatic vital signs, bedside carotid sinus massage, and at least 24 hours of continuous ECG monitoring. The 150 SUO patients included 95 men and 55 women (mean age 62.0 years); 35 had recurrent SUO, 75 (50%) had organic heart disease, and 129 (86%) had abnormal ECGs. There were 162 abnormal electrophysiologic findings that could explain the SUO uncovered in 112 patients, a diagnostic yield of 75%: one finding in 71 patients, two findings in 32, and three findings in nine. These findings were: His-Purkinje disease in 49 patients (30%), inducible ventricular arrhythmias in 36 (22%), AV nodal disease in 20 (12%), sinus node disease in 19 (12%), inducible supraventricular arrhythmias in 18 (11%), carotid sinus hypersensitivity (not elicited by carotid sinus massage prior to electrophysiologic studies) in 15 (9%), and hypervagotonia in five (3%). When electrophysiologic study findings were classified as clearly abnormal or borderline, 54 patients had at least one clearly abnormal finding, a diagnostic yield of 36%. Subgroups of patients presenting with only a single SUO event, no evidence of organic heart disease, or normal baseline ECGs all had substantial diagnostic yields during electrophysiologic studies. Follow-up data in 137 patients (91%) (mean 31 months) showed recurrences in 16 of 34 patients (47%) without and 15 of 103 patients (15%) with electrophysiologic findings despite therapy directed by electrophysiologic testing (p less than 0.0005). This study and a review of the literature indicate that electrophysiologic testing is useful in elucidating the causes of SUO and directing therapy. A significant number of patients benefit from electrophysiologic studies, even when only clearly abnormal findings are considered diagnostic, when only a single syncopal event has occurred, or whether or not organic heart disease or an abnormal ECG is present. PMID- 4025123 TI - Aberrant systemic artery-pulmonary vein fistula: detection of an occult lesion by contrast echocardiography. PMID- 4025124 TI - Atrial flutter causing mid-diastolic closure of Bjork-Shiley mitral prosthesis. PMID- 4025125 TI - Pulsed Doppler assessment of pulmonary vein obstruction. PMID- 4025126 TI - Pericardial mesothelioma: hyaluronic acid in pericardial fluid. PMID- 4025127 TI - Adverse clinical and hemodynamic effects of oral levodopa in chronic congestive heart failure. PMID- 4025128 TI - Hypokalemia as a cause of cardiac arrest: results of electrophysiologic testing and long-term follow-up. PMID- 4025129 TI - Detection of round floating left atrial thrombus simulating left atrial myxoma by two-dimensional echocardiography. PMID- 4025130 TI - Salutary hemodynamic and sustained clinical beneficial effects of nisoldipine, a new calcium channel blocker, in patients with recurrent ischemia and severe heart failure. PMID- 4025131 TI - Symptomatic sinus bradycardia during concomitant propranolol-verapamil administration. PMID- 4025132 TI - Origin of the left anterior descending coronary artery from the right aortic sinus with intramyocardial tunneling to the left side of the heart via the ventricular septum: a case against clinical and morphologic significance of myocardial bridging. PMID- 4025133 TI - The employee pharmacist: countering the frustration. PMID- 4025135 TI - Addiction: three stories. PMID- 4025134 TI - The impaired pharmacist. PMID- 4025136 TI - Aiding impaired pharmacists: what's being done today? PMID- 4025137 TI - Impairment risk in North Carolina pharmacists. PMID- 4025138 TI - The impaired pharmacist. Setting up a program: how one group went about it. PMID- 4025139 TI - One road to recovery: the Georgia program. PMID- 4025140 TI - Treating alcoholism: a holistic model. PMID- 4025141 TI - The Virginia program to help impaired pharmacy students. PMID- 4025142 TI - What's wrong with APhA? PMID- 4025143 TI - Impairment risk in North Carolina pharmacy students. PMID- 4025144 TI - The law and the impaired pharmacist. PMID- 4025145 TI - Formaldehyde (CH2O) concentrations in the blood of humans and Fischer-344 rats exposed to CH2O under controlled conditions. AB - The effect of exposure to formaldehyde (CH2O) on the CH2O concentration of the blood was determined. Eight male F-344 rats were exposed to 14.4 +/- 2.4 ppm of CH2O for 2 hours and the blood was collected immediately after exposure. Formaldehyde concentrations in the blood were determined by gas chromatography/mass spectrometry. The blood of eight rats unexposed to CH2O was collected and analyzed in the same manner. Measured CH2O concentrations (micrograms/g of blood) were: controls, 2.24 +/- 0.07; exposed, 2.25 +/- 0.07 (mean +/- S.E.). Formaldehyde concentrations in human blood were determined by analyzing samples of venous blood collected before and after exposure of six human volunteers (4 M, 2 F) to 1.9 +/- 0.1 ppm of CH2O for 40 min. Average CH2O concentrations (micrograms/g of blood) were: before exposure, 2.61 +/- 0.14; after exposure, 2.77 +/- 0.28. In neither experiment was there a statistically significant effect of exposure on the average CH2O concentration of the blood. However, human subjects differed significantly with respect to their blood CH2O concentrations, and significant differences (either an increase or a decrease) were found between the CH2O concentrations of the blood taken before and after exposure from some of the subjects, suggesting that blood CH2O concentrations may vary with time. PMID- 4025146 TI - The measurement of whole body vibration in the workplace. AB - A measurement system was developed to assess the amount of whole body vibration to which workers are exposed during routine operation of machinery in an industrial setting. This system is discussed in terms of plant structural design, production levels, direction and intensity of vibrational forces, measuring equipment, proper measurement technique and field application. Comparison of field data with ANSI and ISO fatigue-decreased proficiency boundaries indicated that small press operators were not at an increased risk for impaired work efficiency. Limitations of the field survey are presented and application of this system to other occupational environments is discussed. PMID- 4025147 TI - The effect of moisture on the adsorption of chloroform by activated carbon. AB - The effect of moisture on the ability of a granular activated carbon to adsorb chloroform vapor from a flowing airstream was studied under three test conditions: (1) chloroform and water vapor were introduced concurrently into a dry carbon bed; (2) dry chloroform was introduced into a humidified carbon bed; (3) humidified chloroform was introduced into a carbon bed at the same relative humidity. The criterion for bed performance was the time when the downstream chloroform concentration was 1% of that in the inlet stream. Chloroform concentration was essentially constant at 108 +/- 2 micrograms/cm3; relative humidities (RH) varied from 0 to 97%. No RH effect on the adsorption of chloroform by the carbon was observed in test (1); tests (2) and (3) showed monotonic decreases in chloroform adsorption for RH greater than 40%. These results indicated that, for a dry carbon bed, the 1% breakthrough time for chloroform adsorbed from atmospheres of RH from 13% to 95% was essentially the same as that when RH = 0%. For humidified carbon beds, no change in 1% breakthrough time for chloroform was observed until RH was greater than 40%. PMID- 4025148 TI - Variation of composition with particle size in coal liquid aerosols generated for inhalation toxicology studies. AB - The chemical composition and microbial mutagenicity of aerosols generated by nebulizing two coal oils (solvent refined coal [SRC]-I process solvent [PS] and SRC-II heavy distillate) were found to vary with particle size. Significant quantities of the most volatile components of PS were also present as vapors. Evaporation and condensation processes in oil deposited on surfaces as well as in the aerosol are believed to be important in determining the observed composition changes. Complete physical and chemical characterization of the aerosol should be included in inhalation studies of complex materials since the animals may be exposed to material of quite different composition than that placed in the generator initially. PMID- 4025149 TI - Chlorophenol exposure in sawmills. AB - Personnel exposures to chlorophenols were measured in ten Finnish sawmills where a chlorophenolate salt formulation was used for the blue stain control of sawed wood. The concentrations of chlorophenols in the air were usually well below the occupational limit value of 0.5 mg/m3. However, high concentrations (above 10 mg/m3) were measured inside heated kilns. Additionally, high concentrations were detected in the urine of workers whose skin came into contact with chlorophenol solution, indicating that chlorophenols are rapidly absorbed through the skin. The concentrations of chlorophenols in the air were low in trimming-grading plants where treated boards are handled, but some of the chlorophenols was bound to wood dust which is deposited mainly in the nose. The risks associated with the impurities contained in chlorophenol preparations (chlorinated dibenzodioxins and dibenzofurans) and the need for epidemiologic studies on possible cancer risks in sawmill work are discussed. PMID- 4025150 TI - Health examination and air monitoring evaluation for workers exposed to 2 nitropropane. AB - Comprehensive employee health examinations along with work-place area and personal monitoring were conducted to evaluate potential exposure to 2 nitropropane. The employee cross section included in the study consisted of nearly all workers at the plant. The entire workforce was represented, including those who did not have contact with 2-nitropropane. No adverse health effects were found which could be connected with work experience. Body systems evaluated included: lungs, liver, kidney, blood, skin and cardiovascular. Work area levels at specific locations sometimes exceeded 25 ppm, but personal time-weighted average levels generally were below 25 ppm. PMID- 4025151 TI - An evaluation of the response of some portable, direct-reading 10.2 eV and 11.8 eV photoionization detectors, and a flame ionization gas chromatograph for organic vapors in high humidity atmospheres. AB - Three portable, direct-reading instruments were tested to evaluate their ability to detect organic vapors in high humidity atmospheres. The instruments included two photoionization detectors (10.2 eV and 11.8 eV), and an organic vapor analyzer with a flame ionization detector. The organic vapors used were hexanes, 1,1-dichloroethane, chloroform, trichloroethylene, perchloroethylene, benzene, toluene and chlorobenzene. Relatively impervious gas bags were used to contain atmospheres of low (zero) and high (90 percent) relative humidities for comparisons. The response of the organic vapor analyzer was practically independent of humidity. The responses of the photoionization detectors were influenced by high humidity even though the 10.2 eV lamp did not detect water vapor itself. The photoionization detectors were adjudged to be unsuitable for quantitative sampling of humid confined spaces since the 11.8 eV lamp was sensitive to water vapor and the 10.2 eV lamp showed unpredictable response factors in high humidity. PMID- 4025152 TI - A symposium: Amrinone. Introduction. PMID- 4025153 TI - A symposium: Amrinone. November 11, 1984, Miami, Florida. PMID- 4025154 TI - Comparative vasoactive therapy for heart failure. AB - Dopamine and dobutamine increase myocardial contractility by beta-adrenergic stimulation. Both agents provide significant support for decompensating congestive heart failure (CHF) patients. At the same time, both agents can have significant adverse effects. In 1981, it was reported that amrinone, a bipyridine derivative, produced hemodynamic changes similar to those of dobutamine. To confirm these results, the hemodynamic and clinical effects of amrinone were compared with those of dopamine and dobutamine in 15 consecutive patients with CHF. Although each drug improved maximal cardiac index to a similar extent, dopamine did not decrease pulmonary artery wedge pressure and caused a greater increase in heart rate. Dobutamine and amrinone conferred similar hemodynamic benefits: cardiac index improved from 2.4 +/- 0.2 to 3.4 +/- 0.2 liters/min/m2 with dobutamine and from 2.1 +/- 0.2 to 3.2 +/- 0.2 liters/min/m2 with amrinone. Pulmonary artery wedge pressure decreased similarly: from 19 +/- 2 to 13 +/- 1 mm Hg with dobutamine and from 18 +/- 2 to 12 +/- 1 mm Hg with amrinone. Dobutamine and amrinone produced similar modest decreases in mean arterial pressure and increments in heart rate. Dopamine was poorly tolerated; 5 patients developed such severe adverse reactions that this drug was discontinued prematurely. Dobutamine and amrinone were much better tolerated. Although amrinone caused asymptomatic tachycardia (heart rate increase greater than 20% over baseline) in 4 patients, no patient developed an adverse reaction warranting its premature termination. PMID- 4025155 TI - Electrophysiologic effects of amrinone. AB - Patients with congestive heart failure (CHF) have a high prevalence of complex ventricular arrhythmias. Accordingly, the electrophysiologic effects of new drugs for the treatment of CHF should be studied to determine whether they are safe in this population of patients. Fifteen patients with New York Heart Association functional classes II to IV CHF underwent hemodynamic and electrophysiologic testing during control conditions, and after 10 to 20 micrograms/kg/min of intravenous amrinone (dosages that increased cardiac output and decreased left ventricular filling pressures). All cardioactive drugs were stopped for at least 5 half-lives before entry into the study. Amrinone decreased the atrial effective refractory period from 256 to 240 ms (p = 0.015) and the AV nodal functional refractory period from 374 to 356 ms (p less than 0.05), and enhanced maximal 1:1 AV nodal conduction from 371 to 334 ms (p = 0.006). Prolonged HV intervals were present in 9 of 15 patients and were not affected by amrinone. Holter monitoring was performed in 10 patients during acute oral administration of amrinone. There were no significant changes in the frequency of ventricular extrasystoles or ventricular tachycardia, although the frequency of ventricular couples tended to increase slightly. Amrinone therefore enhances AV conduction and does not appear to have significant arrhythmogenic potential during acute administration. PMID- 4025156 TI - Intravenous amrinone in left ventricular failure complicated by acute myocardial infarction. AB - Hemodynamic dose-response effects of intravenous amrinone were studied in 22 male patients aged 38 to 62 years with left ventricular failure occurring within 18 hours of acute myocardial infarction. After hemodynamic confirmation of a raised left-sided cardiac filling pressure--pulmonary artery occluded pressure greater than 20 mm Hg--patients were randomized to either low-dose infusion of amrinone (200 micrograms/kg/hr for 30 minutes, 400 micrograms/kg/hr for 30 minutes and then 800 micrograms/kg/hr for 30 minutes) or high-dose infusion of the drug (800, 1,600 and 3,200 micrograms/kg/hr sequentially, each for 30 minutes). Hemodynamic measurements were obtained at 1 hour before amrinone and at the end of each infusion step. Low-dose infusion of amrinone resulted in a progressive increase in cardiac output (p less than 0.05) and stroke volume (p less than 0.05) and progressive reductions in pulmonary artery occluded pressure (p less than 0.01) and systemic vascular resistance (p less than 0.05). Systemic blood pressure and heart rate were unchanged. High-dose infusion resulted in a similar increase in cardiac output (p less than 0.05) but no change in stroke volume owing to associated tachycardia (p less than 0.01). There was a significantly greater decrease in pulmonary artery occluded pressure compared with the low-dose infusion (p less than 0.05), and systemic arterial diastolic and mean pressures were also decreased (p less than 0.05). The decrease in systemic vascular resistance was of a similar order to that induced by the low-dose infusion.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4025157 TI - Pathophysiology of cardiac failure. AB - The pathophysiologic cycle of heart failure is initiated by myocardial failure that accompanies a reduction in myocardial contractility secondary to ischemic or myopathic heart disease. Reduction in cardiac output and oxygen delivery to the tissues is followed by vasoconstriction that raises systemic vascular resistance to preserve systemic arterial pressure while maintaining regional O2 availability. As a consequence, however, impedance to left ventricular ejection is increased, creating an additional hemodynamic burden for the failing heart. A vicious cycle ensues. Hemodynamic features of acute cardiac failure include decreases in cardiac output and mixed venous O2 saturation, together with increases in left ventricular filling pressure and systemic resistance. If hypotension is present with failure, there is a markedly decreased cardiac output or an inappropriate increase in systemic resistance. If acidosis is also present with hypotension and failure, cardiac output is severely decreased and lactic acid is increased. A major objective of medical therapy in acute heart failure is to enhance ventricular emptying, thereby increasing cardiac output and O2 delivery while decreasing left ventricular filling pressure, pulmonary venous pressure and vascular resistance. Potent intravenous drugs that have a positive inotropic effect on the myocardium, including amrinone and dobutamine, have been shown to increase ventricular emptying in patients with acute heart failure. Intravenous amrinone improves pump performance without adversely raising myocardial O2 consumption, thereby enhancing myocardial efficiency. These drugs also promote a degree of vasodilation through both direct and secondary effects on the systemic circulation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4025158 TI - Amrinone in the management of low cardiac output after open heart surgery. AB - Hemodynamic effects of amrinone were studied in 2 groups of patients after open heart surgery. Group I consisted of 10 patients with moderate heart failure. In the absence of inotropic agents, their mean cardiac index (CI) was 2.02 +/- 0.41 liters/min/m2 and mean pulmonary capillary wedge pressure (PCWP) 19 +/- 3 mm Hg. Amrinone was administered 24 hours postoperatively by bolus injection (2 mg/kg) and by 12-hour infusions (20 micrograms/kg/min). Hemodynamic data and plasma concentrations were obtained 10 and 20 minutes after the bolus injection and at 1, 4, 8 and 12 hours during infusion. Significant beneficial changes were noted in CI, PCWP, right atrial pressure, systemic vascular resistance and pulmonary vascular resistance. Group II consisted of 5 patients in severe cardiogenic shock (mean CI 1.97 +/- 0.3 liters/min/m2, mean PCWP 28 +/- 8 mm Hg) despite adrenergic agonists in all patients and intraaortic counterpulsation in 2. After these measures, amrinone was given intravenously for 36 to 72 hours as additional inotropic support. Significant improvement was observed in CI, PCWP, right atrial pressure, systemic vascular resistance and pulmonary vascular resistance. Four patients in this group were discharged; 1 patient died after 5 days in acute renal failure and coma grade IV. No serious adverse effects of amrinone were observed in any group II patient.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4025159 TI - Value of programmed stimulation and exercise testing in predicting one-year mortality after acute myocardial infarction. AB - The ability of programmed ventricular stimulation and exercise testing to predict 1-year mortality after acute myocardial infarction (AMI) was investigated in 228 clinically well survivors of AMI. Patients with inducible ventricular tachycardia (VT) or ventricular fibrillation (VF) had a higher mortality rate than those without inducible arrhythmias (26% vs 6%, p less than 0.001). Exercise-induced ST segment change of 2 mm or more was associated with a higher mortality rate than ST change of less than 2 mm (11% vs 4%, 0.05 less p less than 0.10). Of patients who had both tests, 62% had no inducible ventricular tachycardia or ventricular fibrillation and ST change of less than 2 mm, and only 1% died during the first year. Thus, in clinically well survivors of AMI, programmed stimulation is a powerful predictor of first-year mortality; programmed stimulation and exercise testing together predict virtually all deaths within the first year, and they can identify a large group of patients with a very low mortality rate. PMID- 4025160 TI - Efficacy of calcium channel blocker therapy for angina pectoris resulting from small-vessel coronary artery disease and abnormal vasodilator reserve. AB - Abnormal vasodilator reserve of the coronary microcirculation is a frequent mechanism of angina pectoris in patients with angiographically normal coronary arteries. To assess the effect of calcium channel blocking agents on symptoms and exercise capacity, 26 patients shown to have angina pectoris because of abnormally small coronary arteries and limited vasodilator reserve underwent randomized, double-blind, placebo-controlled outpatient study, with 1 month for each period. An unblinded lead-in phase determined the best dose of verapamil (17 patients) or nifedipine (9 patients). Exercise testing using bicycle ergometry was performed at the end of each period. Four patients interrupted the placebo period and 1 patient interrupted both placebo and drug period because of frequent and severe chest pain. While receiving calcium channel blocker drugs, patients who completed both phases of the study recorded fewer episodes of angina (21 +/- 21 vs 35 +/- 27, p less than 0.001) and consumed fewer nitroglycerin tablets (23 +/- 27 vs 41 +/- 50, p less than 0.001) than during the placebo period. Exercise duration was slightly but significantly prolonged (278 +/- 129 vs 231 +/- 136 seconds, p less than 0.025) during drug treatment compared with placebo, and significantly fewer patients terminated exercise with chest pain while receiving drug treatment. Subjectively, 22 of 26 patients felt better on the calcium channel blocker than on placebo. Thus, calcium channel blocker therapy appears to be beneficial in controlling angina and improving exercise tolerance in patients with angina pectoris resulting from abnormally small coronary arteries and limited vasodilator reserve.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4025161 TI - Early positive technetium-99m stannous pyrophosphate images as a marker of reperfusion after thrombolytic therapy for acute myocardial infarction. AB - Fourteen patients with transmural acute myocardial infarction (AMI) were treated with intravenous streptokinase a mean of 4 +/- 1 hours after chest pain and underwent technetium-99m stannous pyrophosphate (Tc-99m-PPi) imaging 7 +/- 2 hours after the onset of chest pain. The early Tc-99m-PPi images were obtained to test the hypothesis that an early, strongly abnormal Tc-99m-PPi image suggests reperfusion. Eleven of 14 patients had early peaking (within 16 hours) serum creatine kinase isoenzyme levels (CK-B) at a mean of 11 +/- 3 hours. Ten of 14 patients had 3+ or 4+ acute Tc-99m-PPi images. Eight of 11 patients had patent infarct-related vessels at cardiac catheterization 15 days after AMI. One patient who had both an early positive Tc-99m-PPi image and CK-B peak level had an occluded infarct-related artery at catheterization. Acute left ventricular (LV) ejection fraction (EF) by radionuclide ventriculography was compared with LVEF on day 15, and improved from 0.37 +/- 0.13 to 0.50 +/- 0.16 (p = 0.004) in the 10 patients with strongly positive acute Tc-99m-PPi images. LVEF also improved from 0.37 +/- 0.12 to 0.49 +/- 0.15 (p = 0.003) in the 11 patients with early peaking serum CK-B values. Three patients without evidence of reperfusion failed to improve the LVEF from the initial value to the one obtained at hospital discharge. Six control patients had acute Tc-99m-PPi images 10 +/- 2 hours after chest pain; none had strongly positive acute Tc-99m-PPi images, and the mean time to peak CK-B was 19 +/- 5 hours.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4025162 TI - Comparison of exercise electrocardiography and quantitative thallium imaging for one-vessel coronary artery disease. AB - The relative value of exercise electrocardiography and computer analyzed thallium 201 imaging was compared in 124 patients with 1-vessel coronary artery disease (CAD). Of these, 78 had left anterior descending (LAD), 32 right and 14 left circumflex (LC) CAD. In patients with no previous myocardial infarction (MI), thallium imaging was more sensitive than the electrocardiogram (78% vs 64%, p less than 0.01), but in patients with previous MI, sensitivity was similar. Further, thallium imaging was more sensitive only in LAD and LC disease. Redistribution was compared with ST-segment depression as a marker of ischemia. Only in patients with prior MI (76% vs 44%, p less than 0.01) and only in LC and right CAD did redistribution occur more often than ST depression. Thallium imaging was more accurate in localizing stenoses than the electrocardiogram (p less than 0.001), but did not always correctly predict coronary anatomy. Septal thallium defects were associated with LAD disease in 84%, inferior defects with right CAD in 40% and posterolateral lesion defects with LC CAD in 22%. The results indicate the overall superiority of thallium imaging in 1-vessel CAD compared with exercise electrocardiography; however, there is a wide spectrum of extent and location of perfusion defects associated with each coronary artery. Thallium imaging complements coronary angiography by demonstrating the functional impact of CAD on myocardial perfusion. PMID- 4025163 TI - Time course of alpha-1-acid glycoprotein and its relation to myocardial enzymes after acute myocardial infarction. AB - The acute phase reactant, alpha-1-acid glycoprotein, binds to a number of basic antiarrhythmic drugs, including lidocaine, quinidine, propranolol, imipramine and disopyramide. Binding to alpha-1-acid glycoprotein accounts for a decrease in free drug fraction and may alter the expected concentration: response relation of drugs particularly when there are unpredictably large or rapid changes in alpha-1 acid glycoprotein. To determine the time course and magnitude of alpha-1-acid glycoprotein for 1 month after acute myocardial infarction (AMI), blood samples were collected from 27 patients, 14 with AMI and 13 with a chest pain syndrome but no AMI. Patients with AMI had a significant increase in alpha-1-acid glycoprotein after 72 hours (mean 153 +/- 35 mg/dl) (p less than 0.05), and the maximum was observed on day 7 (mean 165 +/- 53 mg/dl) (p less than 0.05), returning to baseline by 28 days. There was no significant change in alpha-1-acid glycoprotein in patients with chest pain but no AMI. Regression analysis showed a significant relation between creatine kinase (p less than 0.005) and lactic dehydrogenase (p less than 0.001) vs alpha-1-acid glycoprotein indicating alpha-1 acid glycoprotein concentration is high in patients with large AMI. Changes in binding resulting from alpha-1-acid glycoprotein during AMI could account for misinterpretation of total drug concentration and response to antiarrhythmic drugs acutely, during convalescence and at discharge. PMID- 4025165 TI - Anion-channel blockade with alinidine: a specific bradycardic drug for coronary heart disease without negative inotropic activity? AB - In 14 patients undergoing cardiac catheterization for suspected coronary artery disease, alinidine, 0.6 mg/kg, was administered intravenously to determine its effects on left ventricular (LV) function, coronary blood flow and myocardial oxygen consumption. To assess effects independent of changes in heart rate (HR), measurements were made at spontaneous and matched pacing HRs. At spontaneous HR, alinidine decreased HR from 70 +/- 2 to 61 +/- 3 beats/min (p less than 10(-6]. Peak rate of LV pressure decreased from 1,652 +/- 92 to 1,371 +/- 80 mm Hg/s (p less than 10(-5] and Vmax decreased from 47 +/- 3 to 41 +/- 2 s-1 (p less than 10(-4]. Coronary sinus blood flow decreased from 109 +/- 9 to 89 +/- 7 ml/min (p less than 0.01) and myocardial oxygen consumption from 10.9 +/- 1.0 to 9.0 +/- 0.8 ml O2/min (p less than 0.05). At a matched pacing HR of 98 +/- 3 beats/min before and after alinidine administration, peak rate of LV pressure decreased from 1,984 +/- 124 to 1,793 +/- 106 mm Hg/s (p less than 10(-4] and Vmax from 60 +/- 5 to 56 +/- 4 s-1 (p less than 0.02). Coronary sinus blood flow and myocardial oxygen consumption were not significantly changed at matched pacing HRs. The time constant of the first 40 ms of LV isovolumic relaxation was prolonged by alinidine only during spontaneous HR. Thus, alinidine results in a bradycardia-dependent decrease in myocardial oxygen consumption. It has negative inotropic properties independent of changes in HR and so is not a pure bradycardia-specific agent. PMID- 4025164 TI - Hemodynamic and electrocardiographic effects of fructose-1,6-diphosphate in acute myocardial infarction. AB - Acute hemodynamic and electrocardiographic effects of fructose-1,6-diphosphate (FDP), an agent that is supposed to restore anaerobic glycolytic flux in the ischemic myocardium, were studied in 40 patients with acute myocardial infarction who were grouped into 4 subsets: subset 1, normal (15 mm Hg or less) pulmonary artery (PA) wedge pressure and normal (35 g-m/m2 or greater) left ventricular (LV) stroke work index; subset 2, elevated (more than 15 mm Hg) PA wedge pressure and normal LV stroke work index; subset 3, normal PA wedge pressure and reduced (less than 35 g-m/m2) LV stroke work index; subset 4, elevated PA wedge pressure and LV stroke work index moderately reduced to a range between 16 and 34 g-m/m2. Patients were randomized into an FDP (250 mg/kg body weight in isotonic saline solution intravenously in 20 minutes) and into a placebo group. Each subset contained 5 FDP- and 5 placebo-treated patients. After basal measurements, hemodynamic measurements were reassessed at 60, 90 and 120 minutes from the infusions, while a standard 12-lead electrocardiogram was recorded in the basal state and 120 minutes after infusion. Nonsignificant hemodynamic change was observed in the placebo subsets, and FDP failed to exert any effect in subsets 1, 2 and 3. A 24% (p less than 0.02) increase in cardiac index occurred 60 minutes after FDP in subset 4. LV stroke work index also increased, while PA wedge pressure remained unchanged.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4025166 TI - Efficacy of combination therapy with mexiletine and a type IA agent for inducible ventricular tachyarrhythmias secondary to coronary artery disease. AB - The efficacy of combination therapy using a type IA agent (quinidine or procainamide) and a type IB agent (mexiletine) in suppressing inducible sustained ventricular tachyarrhythmias was studied in 23 patients undergoing serial drug testing with programmed stimulation. All patients had coronary artery disease (CAD) with previous myocardial infarction and abnormal left ventricular function (mean ejection fraction 35%). Fifty-five percent of the patients presented with syncope or cardiac arrest. In 19 patients therapy had failed during empiric trials of 1 to 3 antiarrhythmic agents. All 23 patients had inducible sustained ventricular tachyarrhythmias (18 had uniform morphology sustained ventricular tachycardia (VT) and 5 had ventricular fibrillation [VF]) during control electrophysiologic study, and therapy had failed with a type IA agent and mexiletine alone. The combination therapy of mexiletine and the type IA agent prevented induction of any ventricular tachyarrhythmias in 8 of 23 patients. In 15 patients, the combination significantly prolonged the tachycardia cycle length and reduced the symptoms associated with the induced arrhythmia. Patients more likely to respond to the combination had shorter cycle lengths and polymorphic configuration of the control-induced arrhythmia. The increased efficacy of the combination therapy could not be attributed to higher plasma drug levels for the combination, as there was no significant difference in plasma levels for each drug when given alone or in combination. Thus, the increased efficacy most likely reflects a synergistic electropharmacologic effect of the 2 agents.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4025167 TI - Autonomic dependence of ventriculoatrial conduction. AB - To evaluate the effects of isoproterenol and atropine on patients with poor ventriculoatrial (VA) conduction, 17 patients were studied who did not have 1-to 1 VA conduction during ventricular pacing at a rate slightly faster than sinus rate (group I) and 11 patients were studied who had 1-to-1 VA conduction, but only at constant ventricular pacing cycle lengths longer than 600 ms (group II). Isoproterenol infusion at a rate causing a 20 to 30% increase in sinus rate or up to 4 micrograms/min shortened the ventricular pacing cycle lengths that induced VA block in all group II patients. Atropine administration at a dose causing a 20 to 30% increase in sinus rate or up to a total dose of 2 mg also shortened the ventricular pacing cycle lengths that induced VA block in all group II patients. At similar pacing cycle lengths, isoproterenol and atropine induced shorter VA intervals than control. Nine of 17 group I patients had demonstrable 1-to-1 VA conduction either during isoproterenol infusion or after atropine administration. Of these 9 patients, 1-to-1 VA conduction could be found only during isoproterenol infusion in 3 patients and only after atropine administration in 4 patients. The improvement of VA conduction by these drugs was related to their effects on the atrioventricular node. The change in VA conduction mediated by autonomic changes induced by these drugs may explain why some patients without demonstrable VA conduction during rest may have, under certain circumstances, "endless-loop" tachycardia or paroxysmal supraventricular tachycardia using atrioventricular nodal conduction as the retrograde limb.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4025168 TI - Efficacy of verapamil in exercise-induced ventricular tachycardia. AB - The antiarrhythmic efficacy of verapamil was determined by serial treadmill testing in 16 patients with reproducible exercise-induced ventricular tachycardia (VT). Twelve of the 16 patients responded to verapamil, 0.2 mg/kg intravenously; in 8 of these 12 responders, an oral verapamil regimen of 160 to 320 mg given every 8 hours also prevented exercise-induced VT. Plasma verapamil concentration was significantly higher in the responders than in the nonresponders to intravenous verapamil, but levels were similar in responders and nonresponders to oral therapy. The 8 responders to the oral drug were followed up while receiving verapamil therapy for 6 to 22 months (mean 15), and exercise-induced VT did not recur in any patient. Five of the 8 responders also had concomitant spontaneous VT unrelated to exercise which verapamil suppressed initially as well: 4 remained free of spontaneous VT, while 1 patient had recurrence of spontaneous VT. Thus, in patients with exercise-induced VT, verapamil is a promising alternative therapy to beta-adrenergic blocking agents. The effectiveness of verapamil is consistent with a mechanism of arrhythmogenesis involving calcium channels. PMID- 4025169 TI - Entrainment of ventricular tachycardia by atrial depolarizations. AB - Four patients in whom rapid atrial pacing resulted in transient entrainment of a sustained ventricular tachycardia (VT) are reported. Ventricular fusion was seen in 3 of the 4. The following new observations were made: (1) A single atrial depolarization resulted in ventricular fusion and resetting of a VT, while atrial pacing at a faster rate entrained the same VT but without detectable fusion. This suggests that fusion during entrainment may be a rate-dependent phenomenon. (2) The interval between the last paced beat and the first nonpaced VT beat was different from the pacing cycle length in 3 patients. Two mechanisms accounted for this: the initial forces of each entrained QRS occurring as a result of the pacing wavefront, with fusion taking place only during the terminal forces, and the last entrained cycle exceeding the pacing cycle length by an amount related to the nonfused portion of the QRS, and delay in the presumed reentrant circuit responsible for the tachycardia. One VT was entrained with atrial pacing while ventricular pacing at the same rate resulted in termination, suggesting "site specificity" for termination. It is concluded that entrainment can occur without the criteria previously described as characteristic of it and that additional phenomena may be observed after stimulation that further support reentry as the mechanism of VT. PMID- 4025170 TI - Electrical alternans in wide complex tachycardias. AB - The occurrence of electrical alternation of 0.1 mV or greater of the QRS or T wave was analyzed in 156 electrocardiograms that showed wide QRS complex tachycardias from 91 patients. One hundred thirty-six ventricular tachycardias (VT) were recorded from 74 patients and 20 supraventricular tachycardias (SVT) from 17 patients. Alternans was present in 42 tracings (27%) from 35 patients (38%) and was equally frequent in the patients with VT (39%) and those with SVT (35%). Alternans occurred in 36 VTs (27%) and 6 SVTs (30%). Tachycardias with alternans had a shorter mean cycle length than tachycardias without alternans (339 +/- 53 vs 368 +/- 85 ms, p less than 0.05), but were not associated with a particular QRS morphology or axis. Alternans was most frequent in leads V2 and V3 and was seen in more leads during SVT than VT (7.2 +/- 2.6 vs 3.7 +/- 2.5, p less than 0.005). All SVTs with alternans incorporated an atrioventricular bypass tract. Electrical alternans occurs frequently in wide QRS tachycardias. Alone, it does not help differentiate VT from SVT. SVTs utilizing bypass tracts frequently show alternans even if the QRS is wide, and this finding may be useful in determining the mechanism of SVTs with aberrant intraventricular conduction. PMID- 4025171 TI - Programmed electrical stimulation and long-term follow-up in asymptomatic, nonsustained ventricular tachycardia. AB - Thirty-three patients with ventricular tachycardia (VT) (3 or more beats, less than 30 seconds in duration, rate more than 100 per minute) on 24-hour Holter monitoring and no history of clinical arrhythmia (presyncope, syncope or sudden death) were studied using programmed electrical stimulation (PES). PES induced VT in 14 patients (42%), sustained VT in 7 (21%) and nonsustained VT in 7 (21%). Inducible VT was associated with underlying heart disease in 9 of 19 patients with coronary artery disease, 3 of 6 patients with idiopathic dilated cardiomyopathy and 2 of 4 patients with mitral valve prolapse. Patients without structural heart disease did not have inducible VT. Ejection fraction (EF) was not significantly different in patients with or without inducible VT. Twenty three patients were discharged with drug therapy and 10 patients without therapy. At 23 +/- 16 months (mean +/- standard deviation) follow-up, 28 patients (85%) were alive, 4 (12%) had died from a cardiac cause (EF 49 +/- 17% vs 28 +/- 20%, p less than 0.03). Another patient died from cerebrovascular accident. Twenty-six patients (79%) were free of clinical arrhythmia and 7 patients (21%) had arrhythmic events (EF 49 +/- 18% vs 31 +/- 17%, p less than 0.04). Two of 8 patients with noninducible VT who were discharged without drug treatment had clinical arrhythmic events and neither of 2 patients with inducible VT discharged off drugs had such events.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4025173 TI - Doppler hemodynamic evaluation of prosthetic (Starr-Edwards and Bjork-Shiley) and bioprosthetic (Hancock and Carpentier-Edwards) cardiac valves. AB - One hundred thirty-four patients with prosthetic or bioprosthetic heart valves were investigated with Doppler echocardiography to determine normal values for commonly used prosthetic valves and to test the specificity of abnormal Doppler findings. In 70 patients the aortic valves had been replaced and in 64 the mitral valves had been replaced. Gradients across prostheses in the aortic position were calculated from maximal velocity. Peak calculated aortic transvalvular gradients in normal subjects were 22 +/- 10 mm Hg in 33 Bjork-Shiley valves, 23 +/- 10 mm Hg in 27 porcine valves and 29 +/- 13 mm Hg in 6 Starr-Edwards valves. Mild aortic regurgitation was seen in 42% of Bjork-Shiley valves, 26% of porcine valves and 2 of 6 Starr-Edwards valves. Mitral valve orifice was calculated by the pressure half-time method. In clinically normal patients with mitral valve prostheses, the effective mitral valve orifice was 2.5 +/- 0.8 cm2 in 35 Bjork Shiley valves, 2.1 +/- 0.7 cm2 in 17 porcine valves, and 2.0 +/- 0.3 cm2 in 10 Starr-Edwards valves. Mitral regurgitation was found in 11% of Bjork-Shiley valves, 19% of porcine valves and 30% of Starr-Edwards valves. Repeat studies at 2 weeks to 14 months revealed no difference in 8 aortic and 14 mitral prostheses. Seven aortic and 4 mitral valves functioned abnormally as determined by Doppler, and the abnormal function was confirmed in each at surgery or at cardiac catheterization.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4025172 TI - Single and combined therapy for systemic hypertension with propranolol, hydralazine and hydrochlorothiazide: hemodynamic and neuroendocrine mechanisms of action. AB - The antihypertensive mechanisms of single and combined therapy with a beta adrenergic antagonist (propranolol) and a vasodilator (hydralazine) were investigated in 9 patients with moderately severe hypertension, who were receiving maintenance diuretic (hydrochlorothiazide) treatment. Hemodynamic and neuroendocrine responses were determined at rest and during lower body negative pressure, and dynamic and static exercise stress after the chronic administration of propranolol and hydralazine, given alone or in combination. All 3 drug regimens, each administered for at least 10 weeks, reduced blood pressure (p less than 0.05) compared with diuretic-only therapy in patients at rest, in both the supine and standing position, and during lower body negative pressure and dynamic exercise. There was a significant additive antihypertensive effect when propranolol and hydralazine were combined. Only combination therapy effectively lowered pressure during static exercise. The regimens produced divergent effects on the supine cardiac output: a decrease with propranolol (p less than 0.05), no change with combination therapy and an increase with hydralazine (p less than 0.05). Both hydralazine and combination therapy significantly reduced supine total peripheral resistance (p less than 0.05), whereas propranolol produced no change. All 3 drug treatments significantly reduced total peripheral resistance during upright rest and dynamic exercise (p less than 0.05), without changing cardiac output or maximal exercise capacity. During exercise, cardiac output was maintained in patients treated with propranolol and in those treated with combined therapy by increases in stroke volume (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4025174 TI - Doppler versus contrast echocardiography for diagnosis of tricuspid regurgitation. AB - Sixty-eight patients (mean age 49 years) were studied with contrast echocardiography (CE) and Doppler echocardiography (DE) to evaluate both methods for detecting and grading tricuspid regurgitation (TR). In all patients, right ventricular (RV) angiography was performed. The severity of TR was graded on a 4 point scale. Only 68 of 88 patients who underwent RV angiography (77%) could be evaluated, but 65 of 68 patients who underwent CE (96%) and all 68 who underwent DE (100%) could be evaluated. TR was present in 33 patients as seen on RV angiography. CE and DE correctly diagnosed 27 and 30 patients, respectively, corresponding to a sensitivity of 82% for CE and 91% for DE. Specificity was 100% for CE and 86% for DE. CE and DE grading, respectively, of TR vs RV angiographic grading showed no difference in 50 and 47 patients, a 1-level difference in 8 and 13 and a 2-level difference in 7 and 5 cases. (CE-RV angiography, r = 0.84, p less than 0.001; DE-RV angiography, r = 0.82, p less than 0.001). Thus, CE and DE are accurate methods for routine diagnosis of TR, with DE having higher sensitivity and easier grading. Considering the possibility of false-positive findings of our standard RV angiography, sensitivity and specificity of CE and DE could be even higher. PMID- 4025175 TI - Determinants of prognosis in idiopathic dilated cardiomyopathy as determined by programmed electrical stimulation. AB - The incidence and prognostic significance of electrically induced ventricular arrhythmias were prospectively assessed in 42 patients with idiopathic dilated cardiomyopathy. All patients underwent 24-hour, long-term electrocardiographic (Holter) monitoring and 30 were analyzed by a signal-averaging vectorcardiographic procedure at entry into the study. Their response to programmed electrical stimulation during basic right ventricular pacing was investigated using 1 and 2 ventricular extrastimuli. A monomorphic tachycardia was not induced in any patient. In 36 patients (86%) polymorphic ventricular arrhythmias were initiated. Three or more induced consecutive ventricular premature complexes occurred in 9 patients (21%), nonsustained polymorphic ventricular tachycardia in 2 (4.8%) and ventricular fibrillation in 1 patient (2.4%). There was no association between electrically induced polymorphic ventricular arrhythmias and the degree of impairment of left ventricular function. Furthermore, the incidence of induced ventricular arrhythmias was not related to the Lown grade or to the total number of ventricular premature complexes during Holter monitoring. A late potential was detected by the averaged vectorcardiogram in only 1 of the 30 patients. During follow-up (mean 16 +/- 7 months) 7 patients died, 5 from chronic congestive heart failure and 2 from sudden cardiac death. No patient had an electrically induced arrhythmia of 3 or more ventricular premature complexes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4025176 TI - Detection of intracardiac shunt flow in atrial septal defect using a real-time two-dimensional color-coded Doppler flow imaging system and comparison with contrast two-dimensional echocardiography. AB - To evaluate the noninvasive detection of shunt flow using a newly developed real time 2-dimensional color-coded Doppler flow imaging system (D-2DE), 20 patients were examined, including 10 with secundum atrial septal defect (ASD) and 10 control subjects. These results were compared with contrast 2-dimensional echocardiography (C-2DE). Doppler 2DE displayed the blood flow toward the transducer as red and the blood flow away from the transducer as blue in 8 shades, each shade adding green according to the degree of variance in Doppler frequency. In the patients with ASD, D-2DE clearly visualized left-to-right shunt flow in 7 of 10 patients. In 5 of these 7 patients, C-2DE showed a negative contrast effect in the same area of the right atrium. Thus, D-2DE increased the sensitivity over C-2DE for detecting left-to-right shunt flow (from 50% to 70%). However, the specificity was slightly less in D-2DE (90%) than C-2DE (100%). Doppler 2DE could not visualize right-to-left shunt flow in all patients with ASD, though C-2DE showed a positive contrast effect in the left-sided heart in 9 of 10 patients with ASD. Thus, D-2DE is clinically useful for detecting left-to right shunt flow in patients with ASD. PMID- 4025177 TI - Acute hemodynamic effects of nitroprusside in children with isolated mitral regurgitation. AB - The acute hemodynamic responses to nitroprusside during cardiac catheterization were evaluated in 12 children with isolated mitral regurgitation (MR) of congenital origin. The patients were classified into 2 groups. Group I consisted of 5 patients who received digitalis or diuretic drugs and group II consisted of 7 patients who received no medication. Hemodynamic measurements were performed using a multisensor catheter system during infusion of nitroprusside at a dose of 2.0 micrograms/kg/min. With nitroprusside, the mean right atrial pressure decreased an average of 50% in group I (from 6 +/- 1 to 3 +/- 1 mm Hg) and 75% in group II (from 4 +/- 1 to 1 +/- 1 mm Hg), and the mean decrease of pulmonary artery wedge pressure was 50% in group I (from 14 +/- 3 to 7 +/- 3 mm Hg) and 56% in group II (from 9 +/- 2 to 4 +/- 1 mm Hg). Administration of nitroprusside also caused a significant reduction in systemic vascular resistance by 40% in both groups (from 25 +/- 6 to 15 +/- 5 U/m2 in group I and from 25 +/- 2 to 15 +/- 3 3 U/m2 in group II), whereas forward cardiac output increased markedly, by an average of 48% in group I (from 3.3 +/- 0.5 to 4.9 +/- 0.9 liters/min/m2) and 58% in group II (from 3.3 +/- 0.3 to 5.2 +/- 0.8 liters/min/m2). No significant differences in hemodynamic response between groups I and II were noted.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4025178 TI - Usefulness of left ventricular volume in assessing tetralogy of Fallot for total correction. AB - Ninety-one patients with tetralogy of Fallot underwent intracardiac repair between 1978 and 1981. One patient died from left-sided heart failure. Retrospective analyses of this death revealed a significant decrease of the left ventricular (LV) end-diastolic volume index (EDVI) of 21 ml/m2 (36% of normal). Results of early postoperative hemodynamic studies after total correction of this anomaly suggested that an EDVI of 30 ml/m2 is the minimal requirement for adequate cardiac output postoperatively. Based on these data, 3 patients with decreased LV volume with EDVI of around 30 ml/m2 were challenged with the primary repair with success, although they required atrial pacing and catecholamine support postoperatively to maintain adequate left atrial pressure and cardiac output. From these results, it is recommended that patients with tetralogy of Fallot and an EDVI of 30 ml/m2 or more can be considered as candidates for the primary repair, but that patients with an EDVI of less than 30 ml/m2 should be palliated once by systemic-to-pulmonary arterial shunt procedures. Subsequent total correction should be performed after sufficient LV growth for those patients. PMID- 4025179 TI - Rest and exercise hemodynamics in pulmonary stenosis: comparison of children and adults. AB - To better understand the hemodynamics of pulmonary stenosis (PS), 24 adults and 53 children with similar degrees of PS who had undergone cardiac catheterization at rest and during supine exercise were retrospectively studied. Three groups were defined. Group I consisted of 9 adults and 18 children with a pulmonary valve area of less than 0.5 cm2/m2; group II, 6 adults and 25 children with a pulmonary valve area of 0.5 to 1.0 cm2/m2; and group III, 9 adults and 10 children with pulmonary valve area of more than 1.0 cm2/m2. The mean ages of the adults were 29, 26 and 22 years for groups I, II, and III, respectively. The mean ages of the children were 11, 10 and 9 years for groups I, II and III, respectively. The pertinent data collected from catheterization included oxygen consumption, cardiac rate and index, arterial venous oxygen difference, stroke index, right ventricular (RV) systolic pressure and RV end-diastolic pressure. Adults and children in groups II and III had an appropriate response to exercise. Group I children responded abnormally by increasing their RV end-diastolic pressure and decreasing their stroke index. In group I adults both of these variables increased. Group I adults exhibited a significantly lower cardiac index at rest and exercise secondary to a significantly lower absolute cardiac rate. Long-standing severe PS results in hemodynamic compromise. Hence, early relief of PS is recommended. PMID- 4025181 TI - A symposium: Cost containment issues in cardiology. PMID- 4025180 TI - Importance of imaging plane for magnetic resonance imaging of the normal left ventricle. AB - Visualization of the left ventricle by magnetic resonance imaging (MRI) is largely a function of imaging planes. The best depiction of the myocardium is possible when the imaging plane is perpendicular to the region of interest. The effect of imaging plane on the visualization of the left ventricle has not been fully described. To assess this effect, 10 normal adults underwent electrocardiogram-gated multiplanar cardiac MRI. The imaging planes being evaluated were standard planes, transverse, sagittal and coronal, and modified planes relating to the left ventricular (LV) long axis: coronal long axis parallel to the ventricular septum (VS), sagittal long axis perpendicular to the VS and transverse short axis perpendicular to the VS and long axis. The myocardium was separated into 9 segments. Using each plane, the LV segments were evaluated for quality of LV depiction. The planes based on the LV long axis were superior to standard planes in depicting the LV segments. PMID- 4025182 TI - Paradox, change and choice: an economist's view of some current health care resource issues. AB - Health care delivery is a major industry in the United States, consuming large quantities of human and physical capital and generating impressive quantities of products, ideas, trained personnel and health services. The focus of current public policy attention upon the medical profession, which has only in this century become a highly respected scientific profession, is not on its substantial accomplishments, but on the health care delivery system as a consumer (generator?) of over 10% of our annual gross national product. The overwhelming focus of current public policy and public sentiment is on cost containment (i.e., developing strategies to limit the flow of resources into the existing health care delivery system). This shift in public sentiment and new focus of public policy is, in some sense, a paradox in view of the spectacular advances in medical science and access to health care that the medical profession has delivered in the last 2 decades. The source of this anxiety and the cause of current initiatives in public policy and private practices with respect to health care is costs. The health care sector has not only consumed more resources than anticipated, but has also been characterized by unusually rapidly escalating prices and skyrocketing government resource commitments. As a result, we are asking new questions and seeking new initiatives. We are asking whether the institutions and practices that characterize the existing health care delivery system are the most suitable arrangements for our future. This article raises some of the issues entailed by these questions and details some of the choices which lie ahead for the health care industry. PMID- 4025183 TI - The effect of cost containment on the practice of cardiology: predictions. AB - When health care cost containment is tied to unit pricing, the system may become price-driven rather than care-driven. Although the incentives engendered by unit pricing may not necessarily result in practices detrimental to the young or the patient with relatively pure disease, the potential for adverse effects on the elderly, the poor and the chronically ill is real. Hospitals will soon emphasize quick turnover, efficiency and intensive care. Diagnostic evaluations and chronic disease care will be moved out of hospitals into physician owned-and-operated facilities and out-of-hospital settings, respectively. The health care system will fractionate, and quality control will require restructuring to achieve the present level of quality assurance. Cardiologists, as well as other physicians, will need to alter their teaching style and teaching locations. Better methods for predicting outcomes will need to be developed; we will no longer have the safety net of following a patient closely and altering management plans according to the patient's response. Cost containment may occur under diagnosis related groups, preferred provider organizations, health maintenance organizations and other prepaid or "capped" systems. There are, however, many issues relative to cost versus quality that need to be resolved if severe detrimental effects on care are to be avoided. PMID- 4025184 TI - Role of technology in controlling health care costs. AB - The objectives of medical technology are to define basic knowledge about the function of the body and to aid in making patients better. Because the escalation of costs for advanced technology has been dramatic, it has been labelled one of the culprits for the great increases in health care costs in the past decade. Yet technology can improve the quality of care while providing mechanisms for lowering costs. Such an approach requires improved productivity. Several approaches to improve productivity, with emphasis on the electronic and computer revolution that has been brought to medicine, are discussed. In addition, it is suggested that the use of technology gives medical staff more time to meet the personal needs of patients. PMID- 4025185 TI - Future trends in the economics of medical practice and care. AB - A revolution is taking place in the American health care industry. The basis for these changes is the rapid escalation of health care costs to nearly 11% of our gross national product. The changes have caused a controversy regarding whether cost containment reduces the quality of medical care. Our present system was built on the premise that the highest quality of health care could be delivered to all fairly and without any form of rationing. This has led to a massive growth in facilities and the number of physicians. In simple economic terms the market factors in the environment should have lowered the cost of care. However, the cost of care has increased even more rapidly than expected. It seems likely that older economic principles must be abandoned to control costs. Price competition, preferred providers and more efficient hospitals must all be encouraged. Overutilization of care must be discouraged by proper incentives, and overpricing by physicians may require fixed cost reimbursement. Two-tiered health care delivery will develop and small segments of the population may receive a lower quality of care. Rationing of care may be a simple alternative. PMID- 4025186 TI - Workshop I: Quality of cardiologic care in the era of cost containment. PMID- 4025187 TI - Workshop II: Cost containment issues in acute myocardial infarction and coronary care management--points of view. PMID- 4025188 TI - Workshop III: Graduate medical education in an era of cost containment. PMID- 4025189 TI - Thermic effect of feeding carbohydrate, fat, protein and mixed meal in lean and obese subjects. AB - The thermic effect of 1.67 MJ (400 kcal) of carbohydrate (glucose), fat, protein and mixed meal were examined in 11 lean and 11 obese subjects by indirect calorimetry. The changes in metabolic rate in response over 90 min period (30-120 min after the meal) to the different meals were compared with that seen after a similar volume of low calorie drink. The thermic effects of glucose and protein were not significantly different between lean and obese subjects. Obese subjects showed very little increase in metabolic rate following ingestion of fat (-0.9 +/ 2.0%, mean +/- SEM) and this was significantly different from that seen in lean subjects (14.4 +/- 3.4%). The thermogenic response to mixed meal was also significantly lower in obese subjects when expressed as percentage change (12.9 +/- 2.3% compared to 25.0 +/- 4.8%). There was no evidence for delay in gastric emptying times for glucose and fatty meal in the six obese subjects in whom these were measured. We conclude that obese subjects show a reduced thermogenic response to fat. PMID- 4025190 TI - Birth weight doubling and tripling times: an updated look at the effects of birth weight, sex, race and type of feeding. AB - Data were collected on 335 infants from birth to age two years whose families were all subscribers to a prepaid medical care plan. Birth weights were not significantly different by race or gender. Doubling time (DT) was significantly later than that reported in the mid-70s. Tripling time (TT) was significantly later than that calculated from the National Center for Health Statistics growth charts. Birth weight was the most significant factor for both DT and TT. Gender significantly affected DT only. Race was directly significant only for DT, but became significant for DT and TT when adjusted for gender and type of feeding. Type of feeding was not significant. The group which tripled birth weight the earliest had a higher percentage of fatter infants and suggest early TT may be useful to indicate infants at risk for obesity. PMID- 4025191 TI - Plasma lipid and lipoprotein response of humans to beef fat, coconut oil and safflower oil. AB - This study's purpose was to evaluate the fasting human plasma lipid and lipoprotein responses to dietary beef fat (BF) by comparison with coconut oil (CO) and safflower oil (SO), fats customarily classified as saturated and polyunsaturated. Nineteen free-living normolipidemic men aged 25.6 +/- 3.5 yr consumed centrally-prepared lunches and dinners of common foods having 35% fat calories, 60% of which was the test fat. The test fats were isocalorically substituted, and each fed for five weeks in random sequences with intervening five weeks of habitual diets. Plasma total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) concentrations among individuals follows the same relative rank regardless of diet. Triglycerides (TG) concentrations among individuals also maintain their relative rank regardless of diet but in a different order from that of the cholesterols. Plasma TC, HDL-C, and LDL-C responses to BF were significantly lower and TG higher than to CO. As compared to SO, BF produced equivalent levels of TG, HDL-C, and LDL-C and marginally higher TC. Thus, the customary consideration of BF as "saturated" and grouping it with CO appears unwarranted. PMID- 4025192 TI - Alterations in adipocyte free fatty acid re-esterification associated with obesity and weight reduction in man. AB - Using a newly developed in vitro technique, the rate of re-esterification of lipolyzed free fatty acids (FFA) in small fragments of human subcutaneous adipose tissue was measured. When related to simultaneous glycerol release, this measure permits the calculation of the molar ratios of glycerol and FFA leaving the adipocyte. In weight-stable, never-obese control subjects the molar ratio of FFA:glycerol leaving the adipocytes is 1.4:1. During fasting, this ratio climbs to 2.7:1, close to the theoretical maximum of 3.0:1. Adipocytes from weight stable obese subjects do not differ significantly from adipocytes of control in regard to this ratio. However, the adipocytes of weight-stable reduced-obese (RO) subjects display a significantly higher FFA:glycerol ratio than the adipocytes of either control or obese subjects. The presence of this fasting-like physiology in adipose tissue from weight-stable RO subjects is of particular interest since these same individuals have other systemic metabolic and subjective findings compatible with caloric deprivation. PMID- 4025193 TI - A comparative study of the effects of white sugar, unrefined sugar and starch on the efficiency of food utilization and thermogenesis. AB - Energy balance studies with weanling rats and mice were carried out to investigate the chronic effects of diets containing white sugar, unrefined sugar, and starch as sole carbohydrate on body composition and energetic efficiency. The results show no significant differences in energetic efficiency and in body composition of both rats and mice fed the different carbohydrate diets. However, there is a tendency for the sugar-fed animals to have higher metabolizable energy intakes, but rarely was this sufficient to increase body energy since there were corresponding increases in metabolic rate. These studies indicate that differences in energy balance between sugar and starch are small and that any increase in thermogenesis that occurred in some of the groups fed sugar-rich diets was in response to the higher energy intake rather than due to a lower efficiency of utilization of sucrose per se. PMID- 4025194 TI - Differences in vitamin B6 status indicator responses between young and middle aged women fed constant diets with two levels of vitamin B6. AB - The responses of adult women to two levels of vitamin B6, was conducted with five young and eight middle-aged subjects. A constant diet (2.3-2.4 mg vitamin B6 per day) was fed for four weeks followed by three weeks of the same diet supplemented with 8.0 mg pyridoxine. Plasma pyridoxal 5'-phosphate (PLP), plasma and urinary vitamin B6, and urinary 4-pyridoxic acid (4-PA) were determined. The older women had significantly lower plasma PLP, plasma and urinary vitamin B6 and slightly higher urinary 4-PA values on normal vitamin B6 intakes. With supplementation, only the difference in urinary total vitamin B6 remained significant. Tryptophan load tests revealed no significant between-group differences in xanthurenic acid or kynurenic acid excretion. These results demonstrate an age-related difference in vitamin B6 status indicators in women under controlled dietary intake of vitamin B6. PMID- 4025195 TI - Evaluation of zinc and copper nutritional status and effects upon growth of southern adolescent females. AB - A biracial sample of twenty-nine 14-yr old and thirty 16-yr old females was evaluated for zinc and copper nutritional status. Socioeconomic, demographic, anthropometric and 24-h dietary recall data were collected and plasma zinc and copper and erythrocyte zinc levels determined. Mean plasma zinc was 83 +/- 15 micrograms/dl; racial differences were significant (p less than 0.05) with plasma zinc levels at 87 +/- 3 micrograms/dl for whites and 79 +/- 3 micrograms/dl for blacks. Mean plasma copper was 119 +/- 24 micrograms/dl and was slightly higher for blacks than for whites. Mean erythrocyte zinc was 8.3 +/- 2.7 micrograms/g and represented 10 times the level of zinc in plasma. Plasma copper levels were positively (p less than 0.05) related to body size. Plasma copper was negatively (p less than 0.05) related to dietary fiber. Other dietary and economic factors did not affect mineral status. PMID- 4025196 TI - Indices of copper status in humans consuming a typical American diet containing either fructose or starch. AB - Twenty-four male subjects originally participated in a study to determine the effects of feeding diets comparatively low in copper (1.03 mg/day/2850 kcal) and containing either 20% fructose or starch on indices of copper status. During the course of feeding the diets for 11 wk, four of the subjects exhibited heart related abnormalities and were removed from the study. Fructose ingestion had no effect on serum ceruloplasmin activity or serum copper concentration but did significantly reduce cuprozinc superoxide dismutase (SOD) activity of erythrocytes as compared to starch. Repletion of the subjects with 3 mg copper/day for 3 wk significantly increased SOD levels in subjects previously fed fructose but not starch. Apparent copper balance was significantly greater when the subjects consumed the fructose as compared to the starch diet. These results suggest that the type of dietary carbohydrate fed can differentially affect indices of copper status in humans. PMID- 4025197 TI - Studies of marginal zinc deprivation in rhesus monkeys: VI. Influence on the immunohematology of infants in the first year. AB - Rhesus monkey infants fed a marginally zinc-deficient diet (4 ppm) from conception through 12 mo of postnatal life were monitored for changes in hematological, biochemical, and immunological parameters. These zinc-deprived (ZD) infants were compared to control infants whose mothers were fed a zinc replete (100 ppm) diet either ad libitum (AL) or pair-fed (PF) throughout gestation and lactation. Blast transformation of peripheral blood lymphocytes to phytohemagglutinin (PHA-P), concanavalin A (Con A), and pokeweed mitogen (PWM), was dramatically depressed in the zinc-deficient (ZD) group. Similarly, ZD infants had reduced polymorphonuclear leukocyte function as measured by chemotaxis to endotoxin-activated plasma and phagocytosis of Candida albicans. Levels of serum IgM were significantly altered in zinc-deficient infants compared to controls. Serum concentrations of IgG and IgA were similar in zinc-deficient and control infants. ZD infants also manifested a hypochromic microcytic anemia at one month of age, reduced activity of the zinc metalloenzyme alkaline phosphatase, and lower activity of SGPT. PMID- 4025198 TI - Urinary catecholamines in iron-deficient rats at rest and following surgical stress. AB - The purpose of this study was to determine catecholamine concentrations both at rest and in response to a surgical stress in iron-deficient and control rats. Twenty-one-day-old rats were randomized to one of two groups which received a diet containing either 6 or 50 mg iron/kg. Three to five days later, when anemia was first detectable, urinary norepinephrine (NE) concentrations were already significantly elevated in the iron-deficient compared to control rats. In contrast, urinary dopamine (DA) became depressed after 10 days of the iron deficient regimen. At 38 days of age, both groups were subjected to a surgical stress. NE and DA became elevated over baseline values in both diet groups during the 24-h period following surgery; NE remained significantly higher and DA significantly lower in the iron-deficient than in the control group. We conclude that changes in urine catecholamine concentration occur early in the development of iron deficiency and that they are characteristic of both baseline and stress conditions. PMID- 4025199 TI - Alcohol consumption, nutrient intake and relative body weight among US adults. AB - Data from the first National Health and Nutrition Examination Survey (HANES I) were analyzed for differences in nutrient intakes based on the amounts of alcohol consumed by US adults, and for relationships between alcohol consumption, calorie intake, and relative body weight. Drinkers had significantly higher intakes of total calories than nondrinkers, but only because of their intakes of alcoholic calories. Among drinkers, the intakes of nonalcoholic calories decreased as alcohol intakes increased, and it was estimated that between 15 and 41% of the alcoholic calories replaced nonalcoholic calories. Despite their higher caloric intakes, drinkers were not more obese than nondrinkers, suggesting that alcoholic calories may be less efficiently utilized than nonalcoholic calories, or may interfere with utilization of nonalcoholic calories. The most salient difference in nutrient intake between drinkers and nondrinkers was the substantially lower carbohydrate intake of drinkers. PMID- 4025201 TI - Rapid sampling and long-term storage of subcutaneous adipose-tissue biopsies for determination of fatty acid composition. AB - The fatty acid composition of fat tissue is a valid indicator of the fatty acid composition of the diet over the preceding 1 to 3 yr. Here we describe a rapid method for sampling of buttock fat without anesthesia. On average, 35 mg can be obtained using a common blood-sampling system. Sampling of 40 subjects takes about 3 h. The procedure caused no more anxiety or discomfort than a routine venipuncture. Application in about 500 subjects has as yet yielded no infectious or other complications. With regard to the fatty acid composition of the biopsy, sampling site (left versus right buttock) was not found to be a source of error. The biopsies could be stored for periods up to 1.5 yr without changes in the fatty acid profile. With this method one can obtain biopsies from a large number of subjects and determine objectively the long-term fatty acid composition of their diet. PMID- 4025200 TI - Dietary intakes of essential nutrients among Mexican-Americans and Anglo Americans: the San Antonio Heart Study. AB - Dietary intakes of essential nutrients were measured as part of a population based investigation of diabetes and cardiovascular risk factors in Mexican Americans and Anglo-Americans in San Antonio, Texas. Twenty-four hour dietary recalls were conducted on 2134 individuals residing in three socioeconomically distinct neighborhoods: low-income, middle-income, and upper-income. Mean intakes of calcium, vitamin A and vitamin C were significantly lower among Mexican Americans than among Anglos. Intake of vitamin C was most affected by socioeconomic status. Females of both ethnic groups consumed less than their RDA for calcium and iron. Intakes of B vitamins, phosphorus, and potassium were adequate, with few ethnic or socioeconomic differences. PMID- 4025202 TI - Eating in the laboratory: is it representative? AB - The degree to which caloric intake of food consumed in a laboratory setting can approximate caloric intake measured under free-living conditions was assessed in the present study. Four men and four women of normal body weight weighed and recorded their food intake for four days (period 1) during which they were eating in their normal home environment. On the following week (period 2) which also lasted 4 days, the subjects consumed all their food in a laboratory setting. Based upon the findings that no significant change in body weight occurred during either period of the study, that no significant difference in paired caloric intake was observed between period 1 and period 2, and that a highly significant intraclass correlation coefficient, ri = .80 (p less than .005) existed between period 1 and period 2, it was concluded that food consumed in a laboratory setting is a reasonable approximation of caloric intake as measured under free living conditions. PMID- 4025203 TI - Ischemic heart disease: footprints through the data. AB - This study addresses the question of whether the rise in ischemic heart disease mortality has been just "a paper epidemic" as asserted in an earlier issue of this journal. Age-standardized death rates, proportions expected to die, mean ages at death, and cause specific contributions to changes in overall life expectancies were calculated for acute and chronic ischemic heart disease and for males and females for the years 1931 to 1980 using published vital statistics data. These multiple analyses reveal: a true epidemic of acute ischemic heart disease has occurred, affecting males exclusively or to a greater degree than females and it is now on the decline, fairly stable and more nearly comparable mortality for both males and females for chronic ischemic heart disease, and continuing problems of classification obscure the true levels of mortality for both the acute and chronic entities. PMID- 4025204 TI - Bridges between nutrition, neuroscience, and behavior. PMID- 4025205 TI - Phenylalanine metabolites, attention span and hyperactivity. AB - The metabolites of phenylalanine, phenylacetate, phenyllactate, phenylpyruvate and phenylethylamine, were measured in the urine of PKU patients. In general correlation was found between serum phenylalanine excretion of these metabolites. However, there were individual variations in the quantities and type of metabolites excreted that could not be explained by blood phenylalanine levels. In a PKU pregnancy large quantities of phenylalanine metabolites were found in urine despite a modest elevation of serum phenylalanine. Increase in the excretion of phenylalanine metabolites was found in patients who were considered to have good blood phenylalanine control. These preliminary studies indicate that the current practice of allowing a wide range of blood phenylalanine in the treatment of PKU may have to be reexamined. Since these metabolites are neurotoxic, they may afford a new parameter for the study of PKU not only regarding the prevention of mental retardation but also with regards to behavior and learning disabilities. PMID- 4025207 TI - Acupuncture therapy in acute abdomen. AB - Acupuncture as a therapeutic measure for abdominal pain was early recorded in Huangdi Neijing ("Yellow Emperor's Canon of Medicine"). Fruitful experiences have been accumulated in the practice of the long historical years. Nowadays acupuncture therapy has become one of the main therapeutic methods in surgical acute abdomen and is widely used clinically. PMID- 4025206 TI - The effects of dietary neurotransmitter precursors on human behavior. AB - The neurotransmitter precursors tryptophan and tyrosine are present in a variety of foods. In order to document possible effects of tryptophan and tyrosine on human behavior, single oral doses of these substances and matched placebos were administered to 20 men in a double-blind, crossover study. Various tests of mood state and performance were then administered. Tryptophan increased subjective fatigue and decreased self-ratings of vigor and alertness, but did not impair performance on any of the tests. Tyrosine produced no effects in our young population compared with placebo, but did decrease reaction time relative to tryptophan. It may be concluded that tryptophan has significant sedative-like properties, but unlike other sedatives may not impair performance. PMID- 4025208 TI - Psychiatric training and therapies in Ayurved. AB - This paper describes the selection and training procedures, ethical codes, metaphysical theories and principles of psychiatric treatments as practiced in Ayurved. Three treatment approaches for psychological disorders are: Ministered therapies (psychotherapies), Performance therapies (rituals), Auto therapies. Other forms of therapies mentioned are herbal, physical and natural. Treatments were administered with benediction. Man was treated as a whole with a psychosomatic approach. Ayurved is still a living science, though much of its knowledge has passed into oblivion. Resurrection of the lost treasure is advocated if the objective of 'Health for All by 2000 A.D.' is to be achieved for countries like India. PMID- 4025209 TI - Acupuncture points of the lumbar plexus. AB - This communication is the fifth in a series of six publications describing acupuncture points by anatomic nomenclature. This article describes acupuncture points in the lumbar region of the posterior body wall, the inguinal and pelvic regions of the lower abdomen, and the medial surface of the thigh and leg. Acupuncture points in these regions are generally established by anatomic features of the lumbar spinal nerves. Nerve branches of the posterior primary rami of the lumbar spinal nerves and the lumbar plexus provide the anatomic basis for acupuncture points in these regions and are used to name the points accordingly. PMID- 4025210 TI - Acupuncture points of the sacral plexus. AB - This is the sixth and final communication in a series describing acupuncture points by anatomic nomenclature. Most acupuncture points on the lateral and posterior surfaces of the lower limb are located along routes of the sacral plexus. These points belong to acupuncture meridians carrying "Yang energy" in the lower limbs. The meridians are traditionally known as the Urinary Bladder on the posterior surface of the lower limb, Gall Bladder on the lateral surface of the lower limb, and Stomach on the anterior surface of the leg and dorsum of the foot. PMID- 4025211 TI - Drug plants and health care. PMID- 4025212 TI - The effect of hydroxycamptothecin in the activity of RNA and DNA polymerases prepared from murine hepatoma cells. AB - Hydroxycamptothecin (HCPT) is an antitumor alkaloid isolated from Camptotheca acuminata indigenous to China. It could reduce the activity of nuclear RNA polymerase II and I(III) of hepatoma cells. HCPT at 25-100 microM caused a remarkable inhibition on DNA polymerase alpha whilst only a slight inhibition on beta. The inhibitory action on alpha was restored by increasing amounts of enzyme or DNA template, but unchanged by varying amounts of substrate. It is suggested that HCPT may exert a stronger inhibition on DNA replication process. PMID- 4025213 TI - Effect of electro-acupuncture on chronic painful conditions in general medical practice--a 4 years' study. AB - A total of 204 consecutive, recalcitrant painful conditions were treated by electroacupuncture and closely observed up to 4 years in a group medical practice in Australia. The majority (151 cases or 74%) had enjoyed significant pain reduction well beyond 3 months. The causes of failure in the remainders were analysed and discussed. The encouraging overall results led to a renewed call for this mode of therapy to be used more widely as an adjunct in family medicine. PMID- 4025214 TI - Acupuncture points of the typical spinal nerves. AB - Typical spinal nerves have six cutaneous branches which reach to the skin of the body wall in the thorax and abdomen. Each of these six cutaneous branches correlates to an acupuncture point. This communication describes acupuncture points found in the thoracic and abdominal walls using anatomic nomenclature relating to cutaneous branches of the spinal nerves. PMID- 4025215 TI - Acupuncture points of the brachial plexus. AB - This publication is the third of a total of six papers intended to name acupuncture points following the anatomic nomenclatures. In the first publication, acupuncture points in the head are named using terminal branches of the trigeminal nerve and the muscles of facial expression. In the second publication, acupuncture points in the neck are named using the cutaneous nerves of the cervical plexus and neuromuscular attachments formed by the spinal accessory nerve on the trapezius muscle. In this third publication, acupuncture points existing on the upper limbs are described following the terminal branches of the brachial plexus. PMID- 4025216 TI - Alternations of Clonorchis sinensis EPG by administration of herbs in rabbits. AB - In order to investigate clonorchicidal activity in vivo, boiled water extracts of 32 species of clonorchicidal raw drugs in vitro were orally administered into rabbits infected with Clonorchis sinensis. The results of the observation of EPG variation were as follows: Suppression effects of egg-laying capacity from the rabbits administered Prunus mume and Inula helenium were greatest. Those from Dictamnus dasycarpus and Saussurea lappa were somewhat effective. Machilus thunbergii and Cassia obutusifolia, however, were less effective. PMID- 4025217 TI - The effects of Ba-wei-wan (hachimijiogan) on plasma levels of high density lipoprotein-cholesterol and lipoperoxide in aged individuals. AB - Ba-wei-wan was administered for 7 months to 24 aged, non-hospitalized subjects. Laboratory examinations showed an improvement in serum or plasma levels of total lipid, LPO and HDL-C. Other blood examinations were shown to be unaffected by the treatment. To reconfirm the effects of Ba-wei-wan on lipid metabolism, the three step administration of the drug was employed. The elevation of HDL-C levels and the decrease of LPO levels were obtained by this treatment. The discontinuation of this drug induced the converse effect on the plasma levels; decreased HDL-C and increased LPO. It could be concluded from these results that Ba-wei-wan administration improved the lipid metabolism in the aged subjects. PMID- 4025218 TI - Quantitative analysis of ginsenosides in fresh Panax ginseng. AB - TLC, DCC and HPLC were used to study the ginsenoside composition of the main root, lateral root, rhizome, leaves and seeds of Panax ginseng cultivated in Jilin, China. Each of these methods has advantages of its own and the ensemble reveal the special features of Jilin ginseng. Total saponin content of various plant parts in Jilin ginseng showed a mid-range value as compared to those in ginsengs reported in literature. Fresh as well as sun-dried specimens from the same batch possessed a high percentage of Rg1 in the main root and this might account for the traditional preference of this plant part despite its lowest percentage of saponin in the whole plant. Large amounts of polar saponins were also observed in roots and rhizome of fresh Jilin ginseng, the nature and significance of which remained to be investigated. PMID- 4025219 TI - Ginsenoside compositions of Panax ginseng C.A. Meyer tissue culture and juice. AB - By TLC, DCC and HPLC analysis, ginsenoside compositions of ginseng tissue culture and juice showed distinct features of fresh materials by a high proportion of "polar saponins" and low panaxadiol/panaxatriol ratio. PMID- 4025220 TI - Myelodysplasia in the acquired immune deficiency syndrome. AB - Certain new hematologic findings in eight homosexual or bisexual patients with the acquired immune deficiency syndrome (AIDS) are presented. All eight patients manifested a normochromic, normocytic anemia, and six of eight had granulocytopenia during their hospitalization. The other two had low-normal granulocyte counts. Bone marrow examination showed normocellular or hypercellular marrows with increased myeloid: erythroid ratios and increased numbers of megakaryocytes. All patients had abnormalities in maturation of all cell lines, most prominent in the granulocytic series. This constellation of features is similar to the findings in the myelodysplastic syndromes (preleukemia). The authors suggest that myelodysplasia in patients with AIDS results in ineffective hematopoiesis and contributes to the peripheral blood cytopenias found in these patients. Myelodysplasia could be a direct or indirect effect of human T lymphotropic retrovirus-III (HTLV-III). PMID- 4025221 TI - Fluorometric assay of antithrombin III. Diagnostic value in 112 patients with abnormal hemostasis. AB - The authors assessed the diagnostic value of the plasma anti-thrombin III (AT III) assay in 112 adult hospitalized patients with abnormal hemostatic parameters, using the Protopath procedure. In 100 patients tested only once, low AT III was observed in 25 of 29 cases of acute disseminated intravascular coagulation (DIC); 7 of 10 with infections; 8 of 11 with acute liver disease; 19 of 20 with chronic liver disease; and 16 of 30 with other illnesses. The authors conclude that the assay cannot distinguish among disease categories, although it is a sensitive index of DIC. AT III was also repeatedly measured at various time intervals in 12 additional patients. The results suggest enhancement of the diagnostic and prognostic value of the assay with serial testing. PMID- 4025222 TI - Acute thrombotic complications of myeloproliferative disorders in young adults. AB - Two young adults with myeloproliferative disease had recurrent thrombotic episodes, which were life threatening or associated with a risk of serious disability. Both patients were treated for arterial occlusive disease, and treatment in one instance reversed spastic paraplegia. During a subsequent two year period of observation, they have remained symptom free. During that time they have been treated with aspirin, and platelet counts have been maintained at one million/mm3 or less. PMID- 4025223 TI - Calibration bias and imprecision for automated hematology analyzers. An evaluation of significance of short-term bias resulting from calibration of an analyzer with S Cal. AB - A Coulter S + IV analyzer was used both before and after recalibration with S Cal to analyze a series of patient blood specimens and stabilized control specimens. A statistically significant bias was introduced as compared with results on the same analyzer calibrated to fresh whole blood, but the degree of bias did not appear to approach medical significance when compared with two external theoretical models for determining acceptable bias in hematology analysis. Long term bias accumulation on analyzers calibrated to control or stabilized calibration material remains a problem that must be addressed by further study. PMID- 4025224 TI - A simple and practical technic for detecting cancer cells in urine and urinary bladder washings by flow cytometry. AB - DNA measurement by flow cytometry has been demonstrated to be a potentially useful technic in the diagnosis of bladder cancer by detecting neoplastic cells in bladder washings and urine specimens. The authors' goal was to develop a simple and practical method utilizing the new generation of cytofluorographs designed for use in the clinical laboratory. This method combined direct fixation with cell lysis yielding fixed intact nuclei. Following RNase and pepsin digestion, the nuclei were separated from debris and aggregates on a sucrose barrier, stained with ethidium bromide, and analyzed with an argon laser analytic cytofluorograph. Urines and bladder washings from 14 patients with positive urinary cytology and histologically diagnosed bladder cancers were compared with specimens from patients without urothelial malignancies. DNA histograms clearly delineated aneuploid from diploid populations and often identified S, G2M, and G1 phase nuclei. Aneuploid populations have been detected in all tumor specimens with positive cytologies studied to date. PMID- 4025225 TI - The flexible budget process--a tool for cost containment. AB - This past year the authors have been using a new tool to examine and monitor their laboratory's expenditures. Called "flexible budgeting," this process has been used to analyze the cost behavior of all operating expenses, establish budget levels for different levels of activity, and monitor activity based on relative cost rather than simply the number of tests performed. The authors' experience has shown that this tool provides much more information than previous procedures. However, better methods need to be developed for monitoring expenditures so that this information can be used effectively. PMID- 4025226 TI - Is pain crisis a cause of death in sickle cell disease? AB - It has been a matter of controversy as to whether patients with sickle cell disease die of crisis or merely in crisis. The authors reviewed the 74 patients with sickle cell disease autopsied at The Johns Hopkins Hospital. From clinical review, there were 20 (27%) who died with pain crisis, 51 (69%) who died without pain crisis, and 3 (4%) for whom documentation was insufficient. On pathology review, death was attributable to infection in 19 (26%), uremia in 9 (12%), sequestration crisis in 9 (12%), necrotic bone marrow emboli in 7 (9%), and miscellaneous causes in 14 (19%); in 16 (22%) patients no cause of death could be identified. Death was explained in 47/51 (92%) patients without pain crisis; but only in 11/20 (55%, P less than 0.01) patients dying in pain crisis. The disproportionately large number of patients dying in pain crisis with an unexplained cause of death suggests that pain crisis may account for the death of some patients with sickle cell disease. PMID- 4025227 TI - The use of the cytocentrifuge in the diagnosis of meningitis. AB - A retrospective case-control records review was conducted to determine the usefulness of the cerebrospinal fluid (CSF) cytocentrifuge in the diagnosis of meningitis. Over a two-year period, 7,114 records were reviewed, from which 53 cases of aseptic meningitis (AM) and 22 cases of bacterial meningitis (BM) were obtained. Twenty-four cases, judged to be free of meningeal disease, obtained during a three-week period in July 1982, were used as controls. The mean percent polymorphonuclear leukocytes by cytocentrifuge was 14.5% +/- 25.4% in controls, 34.2% +/- 29.6% in AM patients, and 86.4% +/- 13.3% in BM patients. Statistically significant differences existed between the means of each group when compared overall (P less than 0.001) and when each group's mean was compared pair-wise to the two other group means in the study (P less than 0.01 to P less than 0.001). Knowledge of the percent PMNs by cytocentrifuge may be useful in distinguishing patients with meningitis, particularly bacterial, from those free of meningeal disease. PMID- 4025228 TI - Nevus cells within lymph nodes. Possible metastases from a benign intradermal nevus. AB - Two axillary lymph nodes from a patient who underwent modified radical mastectomy for carcinoma of the breast showed benign nevus cells in the fibrous capsule and within afferent lymphatics. Subsequently, an intradermal nevus from the area of drainage of the axillary lymph nodes was excised, which showed groups of nevus cells lying within small lymphatic channels. It is postulated that the nevus cells in the lymph node capsule could represent benign metastases from the intradermal nevus. PMID- 4025229 TI - Human eastern equine encephalitis. Electron microscopic study of a brain biopsy. AB - An electron microscopic study was done on brain biopsy tissue from an eight-month old female with acute eastern equine encephalitis diagnosed by indirect immunofluorescence. Rare clusters of round virions were found almost exclusively in the extracellular space. All virions observed had spiked envelopes, and their sizes averaged approximately 55 nm. Also found were rare enveloped virions along with degenerate organelles in a membrane-bound structure in the cytoplasm of macrophages. Intracytoplasmic development of virions was not found. Tubuloreticular complexes were seen in the endothelial cells and macrophages. This is the first report of an electron microscopic study on biopsy material from a case of human eastern equine encephalitis. It will extend the usefulness of brain biopsy in the diagnosis of acute encephalitis. PMID- 4025230 TI - Detection of circulating T-activating enzyme in the serum of a patient having hemolytic-uremic syndrome and disseminated intravascular coagulation. AB - A three-and-a-half-year old boy suffering from streptococcal pneumonia developed hemolytic-uremic syndrome and disseminated intravascular coagulation (DIC). His red blood cells (RBC) were shown to be T- and Tk-activated; serial testing showed his mature RBCs as well as neocytes remained T-activated at 40 days. Anti-T was detected in his serum, with only one of two T-activated RBC samples. T-activating enzyme was shown to be present in his serum. PMID- 4025231 TI - Acquired Pelger-Huet anomaly associated with Mycoplasma pneumoniae pneumonia. AB - A case report of a healthy 33-year-old man with Mycoplasma pneumoniae pneumonia who concomitantly had the acquired Pelger-Huet anomaly develop is presented. Up to 31% of his total white blood cell count was comprised of Pelger-Huet cells at the height of his clinical illness. The Pelger-Huet cell count returned to 0% after doxycycline therapy and resolution of the pneumonia. No other explanation for the Pelger-Huet anomaly could be determined. A review of the pertinent hematologic literature is included. PMID- 4025232 TI - Falsely elevated serum creatinine levels secondary to the presence of 5 fluorocytosine. AB - The Kodak Ektachem (Eastman Kodak Co., Rochester, NY) is a new clinical chemistry analyzer that uses an enzymatic method to measure creatinine. The authors report the case of a patient with falsely elevated creatinine levels that were caused by the presence of 5-fluorocytosine. A review of the literature confirmed that this can occur, but well documented reports are not found. In order to determine the magnitude of this interference, the authors plotted creatinine levels versus 5-FC concentration. Significant interference is seen with therapeutic levels of 5-FC. Both clinicians and pathologists should be aware of this phenomenon. PMID- 4025233 TI - Marijuana and fungal infection. PMID- 4025234 TI - Mucoepidermoid carcinoma tumor of the rectum--discard the term? PMID- 4025235 TI - mHz, not Hz (in the interest of science) PMID- 4025236 TI - Morphometric studies need review by statisticians. PMID- 4025237 TI - Morphology of follicular centers in persistent generalized lymphadenopathy. PMID- 4025238 TI - Prolonged Simplate bleeding time in hemophilia A: a relationship to age? PMID- 4025239 TI - Duplicate coagulation assays warranted. PMID- 4025240 TI - Usefulness of tests for bacteriuria--my conclusions differ. PMID- 4025241 TI - The 1984 Division 27 award for distinguished contributions to community psychology and community mental health: George Spivack and Myrna B. Shure. PMID- 4025242 TI - ICPS and beyond: centripetal and centrifugal forces. PMID- 4025243 TI - Decision making and job satisfaction among youth workers in community-based agencies. AB - Sixty-four counselors and 32 alternative school teachers in 13 grass-roots agencies reported on levels of participation, influence, and competence in making clinical and administrative decisions. The data supported predictions that (a) professionals would report greater decision-making opportunities and abilities than nonprofessionals, and (b) that workers in general would report higher levels of participation, influence, and competence in clinical than in administrative domains, and higher levels of competence than influence in both domains. However, regression analyses testing the effects of the decision-making variables on different aspects of job satisfaction did not support predicted interactions among participation, influence, and competence. Rather, decision-making involvements had positive effects and decision-making abilities had negative effects on worker morale. The discussion high-lights the need for further research to identify the underlying processes involved in the observed relationships. PMID- 4025244 TI - Crisis prevention and intervention training for psychiatric hospital staff. AB - A 5-day course designed to train psychiatric hospital staff verbal and physical methods of preventing violence and injury when dealing with upset patients was taught to 89 staff from maximum and less secure wards. Compared to no-treatment controls, experimental subjects improved significantly on four tests of crisis related tests and knowledge. Questionnaire and self-report measures from staff and patients on the training wards also indicated positive course effects. Assault frequencies decreased immediately after the course and staff injuries on experimental wards were reduced after the course relative to control wards. PMID- 4025246 TI - Duplicate publication: who is at fault? PMID- 4025247 TI - Duplicate publication and the pursuit of correct references. PMID- 4025245 TI - Mass inoculation in a community: the effect of primary prevention of stress reactions. AB - This study assessed the effectiveness of a brief, situation-specific, group administered preparatory intervention in a nonclient school population undergoing mass inoculation against rubella. Fifty-one girls were randomly assigned to practice, no-practice, or control groups. Both the practice and the no-practice groups received information that described the inoculation procedure and how to cope with it by using cognitive-behavioral coping skills. The practice group was encouraged to perform coping techniques of this type, whereas the no-practice group was told only that the intervention would help them during the inoculation. Subjects in both practice and no-practice groups reported less anxiety and exhibited more cooperative behavior during inoculation than subjects in the control group, and those who were guided and prompted to actively practice derived greater benefit. PMID- 4025248 TI - The education and evaluation of the pediatric resident. PMID- 4025249 TI - Shampoo urethritis. PMID- 4025250 TI - Naloxone in hepatic encephalopathy. PMID- 4025251 TI - RBC transfusion in premature infants. PMID- 4025252 TI - Subacute symmetrical osteomyelitis. PMID- 4025253 TI - Implication of Yersinia species in primary peritonitis. PMID- 4025254 TI - Pseudotumor cerebri following treatment of hypothyroidism. PMID- 4025255 TI - The developmental process of residency education. Issues of stress and happiness. PMID- 4025256 TI - Kawasaki syndrome. Is exposure to rug shampoo important? AB - In the winter of 1982-1983, two clusters of cases of Kawasaki syndrome (KS) provided an opportunity to examine further the possible association among KS, antecedent illnesses, and carpet shampooing and related activities. The two clusters involved 16 patients with onsets between October and January, with seven cases occurring in two adjacent counties in New York (Herkimer and Oneida) and nine in Kent County, Michigan. None of the 11 children with KS included in a case control study had been exposed to shampooed carpets during the month prior to the onset of KS. Only four (36%) of 11 children with KS, compared with 13 (59%) of 22 control subjects, reported a respiratory antecedent illness within 30 days prior to the onset of KS (odds ratio = 0.50, 95% confidence limits = 0.12 to 2.03). The previously observed associations of KS with antecedent respiratory illness and carpet shampooing remain unexplained and undocumented in these outbreaks. PMID- 4025258 TI - Perception of toxicity and dose by 3- and 4-year-old children. AB - Three and 4-year-old children from two suburban preschools were individually interviewed to assess their knowledge of the effects of ingesting a household product, a candy, and a common drug. Most children understood that scouring cleanser was toxic. Children reported that candy was safe to eat, even in large amounts. However, vitamins were not perceived by all children as having a dose related toxicity. This understanding developed with age, and boys were better than girls at differentiating between a usual and an excessive dose of vitamins. One overdose occurred, perhaps because of an increase in the child's interest in vitamins after the interview. More research is needed to broaden our understanding of children's knowledge of the toxicity of poisons. The results of the present study provided information needed for the formulation of educational objectives for a preschool poison prevention program. We believe the primary message is that nothing should be eaten unless it is approved by an adult. PMID- 4025257 TI - Risk factors for neonatal hyperglycemia associated with 10% dextrose infusion. AB - As part of an intensive drug surveillance program, we identified rates and associated risk factors for hyperglycemia related to intravenous 10% dextrose solution in a population of 1,157 newborns in two neonatal intensive care units. Hyperglycemia related to 10% dextrose solution was observed in 64 exposed infants (5.5%), a rate similar to that observed for hypoglycemia (6.7%) in this population. There was a highly significant trend toward an increasing risk of hyperglycemia with decreasing body weight, such that the risk of hyperglycemia among infants weighing less than 1,000 g was 18 times greater than the risk among infants weighing more than 2,000 g. The risk of hyperglycemia also increased with increasing dextrose dose. The effects of weight and dose were independent. Certain measures of disease severity also were associated with increased risks of hyperglycemia. Because increases in blood glucose levels may affect renal function or possibly lead to intraventricular hemorrhage, it is important that glucose levels in neonates receiving 10% dextrose solution be carefully monitored, and the total dextrose dose be adjusted accordingly. PMID- 4025259 TI - Radiological case of the month. Carpal-tarsal osteolysis. PMID- 4025260 TI - Upper- vs lower-limb systolic blood pressure in full-term normal newborns. AB - The difference between upper- vs lower-limb systolic blood pressure (BP) was investigated in 100 normal full-term newborns younger than 24 hours of age by the oscillometric method. The mean systolic BP of both upper limbs was 72.3 +/- 7.6 mm Hg (mean +/- SD). The mean +/- SD systolic BP of both lower limbs was 71.3 +/- 8.2 mm Hg. Systolic BP in the upper limb was greater than that in the lower limb in 66% of newborns by as much as 20 mm Hg (mean +/- SD, 3.5 +/- 3.1). Systolic upper-limb BP was lower than systolic lower-limb BP in 28% of newborns by as much as 21 mm Hg (mean +/- SD, 5.1 +/- 5.1). Systolic BP did not correlate with birth weight. Follow-up evaluation of BP in 25 of the infants up to 3 years of age revealed higher systolic BP in the lower extremities in 24 of the 25 infants. We conclude that (1) it is normal to have a higher systolic BP in either the upper limb or the lower limb in newborns younger than 24 hours of age, and (2) there is no correlation of systolic BP with birth weight in full-term normal neonates younger than 24 hours of age. PMID- 4025261 TI - Clostridium difficile in patients with cystic fibrosis. AB - One hundred seven patients with cystic fibrosis (CF) and 54 other patients with risk factors for Clostridium difficile-associated disease were entered into a bacteriologic study to compare the rate of recovery of C difficile and cytotoxin in feces with occurrence of diarrhea and to investigate potentially protective or permissive relationships of fecal flora. Toxigenic C difficile was recovered from 22% of CF patients and 11% of patients with other diagnoses. Unlike the latter group, the majority (12/15) of CF patients who had cytotoxin recovered had formed stools and no history of diarrhea. Explanations for the lack of symptoms are speculative. Stool flora of CF patients was significantly more likely to include several bacteria with known inhibitory effects on C difficile. Recovery of C difficile and cytotoxin, however, was not associated with the decrease in rate of recovery or the mean bacterial count of any bacterium of fecal flora. PMID- 4025262 TI - The relationship of mode of infant feeding and location of care to frequency of infection. AB - During one year 200 healthy, full-term infants were followed up prospectively for frequency of infection. Infants were categorized by mode of feeding--breast, breast-and-bottle, or bottle--and were subcategorized by location of care and by number of siblings in the home. The average number of infections in infants fed in a day-care or sitter location was 35% greater than that in infants fed at home. The mode of feeding had no bearing on the frequency of infection. PMID- 4025264 TI - Cell-mediated immunity assessed by Multitest CMI skin testing in infants and preschool children. AB - Two hundred twenty-one healthy children, from 6 months to 7 years of age, were tested for delayed-type hypersensitivity (DTH) by the Multitest CMI (cell mediated immunity) (Merieux Institute, Miami). This device permits the simultaneous application of seven standardized recall antigens and a glycerol diluent control. Younger children were tested on the back and older children on the volar surface of the forearm. Only 6.8% of the children were anergic, and most of them (11/15) were female. The DTH responses were present for one or more antigens in 93% of the infants. The DTH responses increased tremendously during the second year of life and increased slowly thereafter. A relatively high incidence of positive reactions was found for three of the tested antigens- diphtheria toxoid (79%), tetanus toxoid (62%), and Proteus (57%), in children in the preschool years, and accounted for three fourths of all positive reactions. Much lower levels were found for Streptococcus (25%), Candida (16%), Trichophyton (5%), and tuberculin (4%). Measurement of DTH by the standardized Multitest CMI system seems to be a convenient and reliable tool for assessing CMI function in infants and small children. The tool permitted us to measure patterns of DTH responses from infancy onward in a healthy population and to develop index values in a normal reference population with which any tested preschool child can be compared. PMID- 4025263 TI - Pattern of bacterial infections in homozygous sickle cell disease. A report from Saudi Arabia. AB - Streptococcus pneumoniae is the leading pathogen in children with sickle cell disease. Forty children younger than 20 years of age who had sickle cell disease and septicemia, meningitis, or osteomyelitis/septic arthritis were identified. The causes included Streptococcus pneumoniae (20%) and gram-negative organisms (mainly Salmonella) (70%). The gram-negative infections occurred in the first decade of life in 45% of our patients. We believe that this pattern of infection is different and related to the mild nature of sickle cell disease in our patients and to their persistent splenic function. The administration of pneumococcal vaccination may also have played a role. Microinfarcts of the intestinal wall allow the access of gram-negative organisms to the circulation. In places where gastrointestinal tract infections, especially Salmonella, are common, antibiotic therapy effective against these organisms is recommended initially with adjustment after identification and sensitivities are known. PMID- 4025265 TI - Rationale of identification based on biological factors of the dentition. AB - Dental traits in the nature of form and size of fissures, cusps, and pits often reflect genetic and phylogenetic interactions in growth and development that are common to other individuals and serve a useful purpose in identification. PMID- 4025266 TI - Malignant hyperpyrexia and sudden death. AB - Two teenage boys, brothers, died suddenly within 2 months of each other. No clear cause of death could be identified in either case. Because of previous reports of the association between malignant hyperpyrexia and sudden death in otherwise healthy young men, we examined the parents. The father was found to be malignant hyperpyrexia-susceptible. PMID- 4025267 TI - Wrapped to death. Unusual autoerotic death. AB - Despite the large population of New Orleans, including many homosexual and transsexuals, there have been relatively few cases of autoerotic deaths. The case reported here is an interesting one as it includes a bizarre form of autoerotic behavior from the standpoint of the method used. There have been no deaths reported in the literature in which the victim died as a result of jeopardizing himself by enclosing his body into plastic with an airway out of his "cocoon" in the form of a snorkel tube. He was engaged in masturbation when he apparently lost his mouth piece or airway. He attempted to use a knife to cut himself out. PMID- 4025268 TI - Sudden unexpected death due to atherosclerotic coronary artery aneurysm. AB - The case of a 34-year-old white male who died suddenly and unexpectedly of a thrombosed coronary artery aneurysm is presented. Coronary artery aneurysms have a prevalence of approximately 2%; over half of these are caused by atherosclerosis with the remainder due to syphilis, infections, trauma, congenital malformations, vasculitis, neoplasms, and connective tissue disorders (Ehlers-Danlos and Marfan's syndromes). Replacement of the media by atherosclerotic debris is the cause of atherosclerotic aneurysms. Complications include rupture and thrombosis. Sudden death has been reported in eight other cases of atherosclerotic aneurysms; sudden unexpected death as the presenting symptom of atherosclerotic coronary artery aneurysm, as in our case, is rare. PMID- 4025269 TI - Sudden asphyxial death due to an esophageal leiomyoma. AB - An exceedingly rare case of an esophageal leiomyoma causing sudden death by asphyxiation due to tracheal compression is presented. A brief discussion of esophageal leiomyomata is included. PMID- 4025270 TI - Injuries to pathologically changed cervical vertebrae. AB - Three cases of fatal injuries to the upper cervical spinal cord and underlying cervical spine pathology are presented. It is stressed that the slightest suspicion concerning injuries to the upper part of the neck must lead not only to microscopic examination of the cervical spinal cord and medulla oblongata, but also to careful preparation (or maceration) of the upper cervical spine, in order not to overlook fractures or misinterpret old fractures and diseases as fresh fractures. PMID- 4025271 TI - Procedure in identifying fingernail imprint in human skin survives appellate review. AB - A case of first impression involving the identification of the person whose fingernail left an imprint on the neck of a child murder victim has survived appeal to the Pennsylvania Superior Court. The appeals court, in an opinion which includes a number of incongruous features, approved the trial court's admission of scientific testimony matching an accused's fingernail to the impression left in the child's neck, apparently during his being manually strangled. PMID- 4025272 TI - Concepts in survival from lethal handgun wounds. AB - Autopsy cases of deaths from handgun wounds were studied. Survival times were estimated from time of the incident until the time of pronouncement on police reports. Two groups were apparent--short-term and non-short-term survivors. These groups were compared statistically with respect to age, race, sex, Spanish surname, alcohol, drugs detected at autopsy, caliber of projectile, frequency of shots, and location of injury. PMID- 4025273 TI - Sudden death associated with pericardial impact. PMID- 4025274 TI - Murder in Taiwan. PMID- 4025275 TI - Return of peristalsis in achalasia after pneumatic dilatation. AB - Distally progressive contraction waves were demonstrated in seven of 34 (20%) patients with achalasia, successfully treated with pneumatic dilatation. There was no correlation between the appearance of such waves and clinical status, the decrease in lower esophageal sphincter resting pressure, or in the radiographically measured diameter of their esophagus. Return of these waves cannot be adequately explained by the "common cavity phenomenon." PMID- 4025276 TI - Pathology of gastrointestinal tract in chronic hemodialysis patients: an autopsy study of 78 cases. AB - The pathological data obtained from postmortem examination of the gastrointestinal tract in 78 chronic hemodialysis patients are reported. All but two of the patients exhibited some gastrointestinal abnormalities. Multiple abnormalities often coexisted in one individual. Esophagitis, gastritis, duodenitis, enteritis, and colitis were seen with considerable frequency. However, extensive hemorrhagic, ulcerative, and pseudomembranous lesions frequently seen in untreated uremia were generally lacking. Evidence of peptic ulcer disease was found in one-fourth of the patients confirming the increased predisposition of dialysis patients to this complication. Several patients exhibited various ischemic phenomena including thrombosis, embolism, and infarction of various segments of the gastrointestinal tract. In addition, numerous other abnormalities were found throughout the gastrointestinal tract with lesser frequency. The data indicate that various gastrointestinal abnormalities commonly occur in patients with endstage renal disease despite uremia control by hemodialysis. However, the observed abnormalities are different from those reported in untreated uremia. PMID- 4025277 TI - Clinical course and evolution of erythema nodosum and pyoderma gangrenosum in chronic ulcerative colitis: a study of 42 patients. AB - The authors examined 1132 patients with chronic ulcerative colitis (CUC) seen at the Cleveland Clinic to clarify the relationship between the clinical features of colitis and the incidence and severity of erythema nodosum (EN) and pyoderma gangrenosum (PG). There were 21 patients (2%) with EN and 21 (2%) with PG, both of which affected those with active and extensive colitis. CUC was inactive in only 10% of the EN group and 20% of the PG group; it was left-sided in 20% of the EN group and 15% of the PG group. The mean duration of CUC before the appearance of EN and PG was 5 and 10 years, respectively. Three patients had consulted a dermatologist for PG before a clinical diagnosis of CUC was made. EN and PG recurred in 20 and 33% of cases, respectively. EN appeared almost exclusively on the legs, while PG appeared on various areas of the skin, including the site of ileostomy in one patient. EN was controlled with adequate medical or surgical treatment of CUC, but PG was relatively refractory, requiring specific treatment of its own in 30% of patients. In one case each, EN and PG recurred after subtotal colectomy but had resolved completely after proctectomy. In one patient, PG developed for the first time 1 year after total colectomy. Less than half of EN patients and two-thirds of PG patients ultimately had to undergo colectomy because of bowel disease. No patient required colectomy because of skin lesions. PMID- 4025278 TI - Does bacteremia occur during flexible sigmoidoscopy? AB - Up to 10% of patients may have bacteremia after rigid sigmoidoscopy. The aim of our study was to determine the frequency of bacteremia accompanying flexible sigmoidoscopy. Blood samples for aerobic and anaerobic cultures were obtained before, during, and after flexible sigmoidoscopy in 100 patients who were examined a mean distance of 49.5 cm, range 15-60 cm, after a bowel preparation of two Fleet enemas. In one patient, a transient bacteremia with Streptococcus intermedius was documented and was attended by no associated clinical manifestations. This organism has been previously isolated from patients with endocarditis, peritonitis, emphysema, and hepatic and appendiceal abscesses. There was no association in our study with bacteremia and such factors as length of bowel examined and duration of procedure, the presence of bowel pathology, performance of endoscopic biopsies, liver disease, and portal hypertension or poor bowel preparation. We conclude that the extremely low incidence of significant bacteremia with flexible sigmoidoscopy may be related to the smaller diameter of the instrument and provides further support for the routine use of flexible rather than rigid sigmoidoscopy. PMID- 4025279 TI - Superior mesenteric venous aneurysm. AB - A patient presented with recurrent upper gastrointestinal bleeding. Celiac and superior mesenteric angiography showed a superior mesenteric venous aneurysm, a normal-sized liver, an enlarged spleen, and esophageal varices. The patient gave no history of hepatitis or alcoholism. It is concluded that the portal hypertension was secondary to aneurysm of the superior mesenteric vein. Aneurysms of the portal venous system can cause chronic portal hypertension due to alteration of blood flow. We believe this to be the second case reported in the English literature of a superior mesenteric venous aneurysm. PMID- 4025281 TI - Choledochal cyst--clinical features and classification. PMID- 4025280 TI - Relapsing acute pancreatitis as the presenting manifestation of an ampullary neoplasm in a patient with familial polyposis coli. AB - The incidence of periampullary carcinoma is increased in patients with familial polyposis coli or the Gardner syndrome. Patients with familial polyposis coli and ampullary tumors usually present with obstructive jaundice or abdominal pain. We report the case of a 41-year-old woman with the Gardner syndrome in whom relapsing acute pancreatitis was the presenting manifestation of an ampullary neoplasm. A diagnosis of ampullary neoplasm should be considered in any patient with familial polyposis coli or the Gardner syndrome and pancreatitis, even in cases of relapsing acute pancreatitis. PMID- 4025282 TI - Preoperative complications of gallstones and their relevance to treatment and prognosis: experience with 451 cases. AB - Of 451 patients with cholelithiasis, 273 suffered from 396 preoperative complications; the common ones were acute cholecystitis (n = 120), jaundice (n = 135), and acute pancreatitis (n = 52). Of the 195 patients under the age of 50 years 48% had complications, compared with 70% of the 256 above the age of 50 years. For acute cholecystitis and acute pancreatitis, an interval cholecystectomy was carried out 3-6 wk after initial conservative treatment. Except in the 33 cases with obstructive jaundice of indeterminate etiology (n = 15) or jaundice associated with uncontrollable cholangitis (n = 18), surgery in icteric patients was deferred until serum bilirubin became normal or reached a plateau. Routine intraoperative radiology detected unsuspected stones in common bile ducts in 11 cases. In all, 139 choledochotomies were carried out; the frequency of ductal exploration rose after the age 50 years. Operative elimination of sphincter of Oddi (by sphincteroplasty or by choledochoduodenostomy) was required in 82 cases. Bile culture was positive in only 17 of 178 cases without preoperative complications but in 97 of 273 with preoperative complications. Of the 21 cases who died, 19 had preoperative complications and 66% had positive bile culture. Nine of 139 requiring choledochotomy died. Mortality after 60 years was 15 of 119. PMID- 4025284 TI - Who should do gastrointestinal endoscopy? PMID- 4025283 TI - Cholecystoduodenal fistula. AB - An elderly woman with a history of cholelithiasis was seen for right upper quadrant pain and jaundice. During her evaluation, she was found to have extensive choledocholithiasis and a cholecystoduodenal fistula. Successful management was accomplished with cholecystectomy, removal of the common bile duct stones, and by creating a choledochoduodenostomy where the fistula had been present. PMID- 4025285 TI - Clinical efficacy of oral 5-aminosalicylic acid in the treatment of inflammatory bowel disease. PMID- 4025286 TI - Lifetime occupational exercise and colon cancer. AB - The authors used data on patients aged 30-79 years admitted to the Roswell Park Memorial Institute in Buffalo, New York, 1957-1965, to compare the amount of lifetime occupational physical activity for 210 white male patients with cancer of the colon and 276 white male patients with cancer of the rectum to the lifetime occupational physical exercise of 1,431 patients with nonneoplastic nondigestive diseases. The authors found that risk of cancer of the colon increased with increasing amount and proportion of time in jobs involving only sedentary or light work. This relationship was not found for rectal cancer. These findings corroborate those of Garabrant et al. (Am J Epidemiol 1984; 119:1005 14). The strength of the associations presented here and the dose-response relationship indicate that limited physical activity could be an important etiologic factor. More inquiries need to be undertaken to study exercise in relation to other factors, such as diet, in colon cancer risk. PMID- 4025287 TI - Ethnic differences in blood pressure and heart rate of Chicago school children. AB - In 1975-1978, the Chicago Department of Health conducted a screening program that included measurements of blood pressure, heart rate, height, weight, triceps skinfold thickness, and arm circumference, and calculation of body mass index and muscle circumference for non-public school children. Based on data on 4,086 boys and girls aged 5-10 years from the program, this study examined the ethnic differences in blood pressure and heart rate among children of white, black, Latino, and Oriental ethnicity. Mean levels for both systolic and diastolic blood pressure were higher for Oriental and black children than for white and Latino children. These differences were independent of age, height, weight, and skinfold thickness. The black children had a much lower mean heart rate than the other children. A seasonal variation was observed for systolic blood pressure, i.e., with each sex group, the mean systolic blood pressure adjusted for age, skinfold thickness, and height tended to be higher in spring than in fall and winter. (Note-- no child was screened during the summer because of summer break.) With control for season, ethnic differences in systolic blood pressure disappeared, but not the ethnic differences in diastolic blood pressure and heart rate. PMID- 4025288 TI - Trace metals and coronary heart disease risk indicators in 152 elderly men (the Zutphen Study). AB - Information about trace metals and coronary heart disease risk indicators was collected in 1977 among 152 men aged 57-76 years in the town of Zutphen, the Netherlands. Serum zinc, serum copper, blood cadmium, and blood lead were determined by atomic absorption spectrometry and serum lithium by flame emission spectrometry. After uni- and multivariate regression analysis, the following statistically significant relations were found: serum zinc was inversely related to resting heart rate; serum copper was positively related to cigarette smoking and inversely to high density lipoprotein cholesterol; blood cadmium was strongly positively related to cigarette smoking and inversely to Quetelet index; the positive relation between blood lead and cigarette smoking was of borderline significance; and blood lead was related to blood pressure, with the relation being stronger for systolic than for diastolic blood pressure. PMID- 4025289 TI - Breast cancer and the consumption of coffee. AB - The hypothesis has been raised that coffee consumption may increase the incidence of breast cancer, based on the report that fibrocystic breast disease, a risk factor for breast cancer, regresses after abstention from coffee and other methylxanthines. The relation between recent coffee consumption and the risk of breast cancer was evaluated in a case-control study, based on interviews conducted 1975-1982 at several mainly eastern US teaching and community hospitals. The responses of 2,651 women with newly diagnosed breast cancer were compared with those of 1,501 controls with nonmalignant conditions and 385 controls with cancers at other sites. The relative risk estimates for levels of coffee drinking up to seven or more cups daily, relative to none, approximated 1.0 with narrow 95% confidence intervals. After allowance for confounding, the relative risk estimate for drinking at least five cups a day was 1.2 (95% confidence interval, 0.9-1.6) using the noncancer controls and 1.1 (0.7-1.6) using the cancer controls. Coffee consumption was not associated with an increase in the risk of breast cancer among women with a history of fibrocystic breast disease, nor were tea or decaffeinated coffee associated with an increase in the risk of breast cancer. The results suggest that the recent consumption of coffee does not influence the incidence of breast cancer. PMID- 4025290 TI - A validation of two motion sensors in the prediction of child and adult physical activity levels. AB - The authors sought to assess the reliability and validity of two motion activity sensors in the prediction of observed physical activity levels in adults and children by means of two studies at North Dakota State University in Fargo, North Dakota. In study 1, 50 adults were observed in fall 1984 for one hour of recreational activity while they simultaneously wore two motion sensors: an activity counter (i.e., LSI Moving Activity Monitor (GMM Electronics Inc., Verona, PA)) and an electronic accelerometer (i.e., Caltrac Personal Activity Computer (Hemokinetics, Inc., Vienna, VA)). The results indicated that both the activity counter (r = 0.65) and the accelerometer (r = 0.69) strongly correlated to observed physical activity levels. The two motion sensors also were highly correlated to each other (r = 0.83). A correlation of self-reports of time spent in various types of physical activity to observed physical activity ranged from 0.21 to 0.88 (mean = 0.60). Study 2 evaluated these same two sensors in winter 1984 in 30 preschool children observed in a freeplay situation. Results of this study indicated very modest relationships between observed physical activity levels and accelerometer readings (r = 0.35) and activity counter readings (r = 0.40). The two motion sensors intercorrelated at very modest levels (r = 0.42). The results indicate that while both motion sensors closely corresponded to observed levels of physical activity in adults, neither sensor correlated substantively to observed levels of physical activity in children. Implications for validating and utilizing these sensors in epidemiologic research are discussed. PMID- 4025291 TI - Acute infections with hepatitis B virus in medical personnel during a 15-year follow-up. AB - Clinical hepatitis B among hospital staff in Sweden was studied in a 15-year follow-up, divided into three periods. During the first 5-year period, 1969-1973, 756 cases of hepatitis B were reported among hospital staff, for an attack rate of 102.0 per 100,000 person-years. In the second five-year period, 1974-1978, the attack rate was 30.4, and in the last five-year period, 1979-1983, it was 10.4. The decrease in incidence between the first period and the second was significant (p less than 0.001), as was the difference between the second period and the last (p less than 0.01). The difference between the incidence in medical personnel and that in the general population of working age in the first period was significant at p less than 0.001 and during the last period it was significant at p less than 0.01. No statistical significance was found during the second period, due to the decrease in incidence for both groups, which made the values too scattered. Traditionally high-risk units, such as renal dialysis units, had only three cases reported in the last 5-year period. An overrepresentation of males among nurses and nursing assistants with acute hepatitis B was found. PMID- 4025292 TI - Community exposure to hazardous waste disposal sites: assessing reporting bias. AB - A household health survey of residents living near two hazardous waste disposal sites in Calcasieu Parish, Louisiana was conducted in 1981-1982 as part of a comprehensive study of the effects of those sites on the environment and on the health of nearby residents. An unexposed community was included in the health survey for comparison. Due to media coverage and public concern about the sites, two potential indices of reporting bias, hypochondriasis and respondent's opinion about the environmental effects of waste sites, were included in the survey. Because air and water quality data showed little evidence that hazardous concentrations of chemicals were being released from the sites, questions were raised about the interpretation of the health survey data. The data were analyzed, therefore, for the association between symptom reports and the potential indices of reporting bias. Hypochondriasis scores were associated with symptom reports regardless of location of residence while an individual's opinion showed a different pattern by area of residence. Respondents living near one of the waste disposal sites who answered "yes" to the opinion question were 2-3 times more likely to report some types of symptoms than residents of the comparison community. In contrast, there was little difference in symptom reports between the exposed and comparison communities for those answering "no" to the opinion question. The usefulness of self-reported symptom data in studies of communities near hazardous waste disposal sites is discussed, and attention is called to the need to develop measures sensitive to reporting bias in epidemiologic studies. PMID- 4025293 TI - Is the relationship between blood pressure and cardiovascular risk dependent on body mass index? AB - The relationship between blood pressure and cardiovascular mortality according to body mass index has been analyzed in two French prospective studies: the Paris Prospective Study, composed of 7,704 men aged 40-53 years examined in 1967-1972, and the Investigations Pre-Cliniques Study, made up of 19,618 men aged 40-69 years who underwent a checkup in 1970-1980. In the Paris Prospective Study, during a mean follow-up of 11.2 years, 241 cardiovascular deaths occurred, while in the Investigations Pre-Cliniques Study, with a mean follow-up of 7.6 years, 262 cardiovascular deaths occurred. A Cox survival analysis was performed on the data of each study to test the interaction of blood pressure and body mass index in the prediction of cardiovascular risk. Both analyses demonstrate a significant negative interaction, suggesting that a decreasing trend of the relative risk of cardiovascular death with increasing body mass index is better supported by the data than a constant relative risk. These results might have some bearing on the problem of the management of hypertension in overweight subjects. PMID- 4025294 TI - Physical fitness and blood pressure: the role of age. AB - Most epidemiologic studies have shown an inverse relationship between resting blood pressure and usual levels of physical fitness or activity. The inference is that fitness lowers blood pressure. However, maximum oxygen uptake (VO2max--a widely accepted measure of fitness) and blood pressure are both correlated with age; young people usually have lower pressures and higher VO2max (ml X kg-1 X min 1). Systolic and diastolic pressures were measured and maximal oxygen uptake was estimated in 184 men and 227 women aged 18-65 years who were randomly selected as part of a cardiovascular risk factor survey conducted in two New England cities between April 1981 and March 1982. Initially, both measures of blood pressure were strongly and inversely correlated with estimated maximal oxygen uptake. However, when the effects of age were partialed out, the strength of the correlations decreased sharply for both males and females. The proportion of the variance in systolic pressure explained by maximal oxygen uptake decreased from 9.6 to 0.8% for males and 21.2 to 2.3% for females. Similar decreases were demonstrated for diastolic pressure in males (14.4 to 2.9%) and females (20.3 to 2.3%). These data indicate that the frequently observed relationship between fitness and blood pressure is strongly influenced by age. Future research to specifically examine the effects of physical activity and of physical fitness on blood pressure is needed. PMID- 4025295 TI - Lipids and lipoproteins in a young adult population. The Beaver County Lipid Study. AB - Though atherosclerosis may have its origins in childhood, intervention studies on coronary heart disease risk factors have usually begun in older adults. Whether young adults exhibit similar relationships of lifestyle to coronary heart disease risk factors, and therefore might be suitable candidates for appropriate intervention, is poorly understood. The Beaver County Lipid Study is a 9-year follow-up study of a free-living young adult population (mean age 22 years) who were initially screened for hypercholesterolemia as seventh grade school children. This report focuses upon cross-sectional correlates of lipid and lipoprotein concentrations in 561 individuals (males n = 262; females n = 299) in 1981-1982. Body mass index was positively related to low density lipoprotein (LDL) cholesterol and triglycerides in men (r = 0.21; p less than 0.001 and r = 0.41; p less than 0.001) and women (r = 0.16; p less than 0.001 and r = 0.20; p less than 0.001). Cigarette smoking was inversely associated with high density lipoprotein (HDL) cholesterol in men (r = -0.11; p less than 0.001) and women (r = -0.20; p less than 0.001) but positively related to triglycerides in both sexes (r = 0.10; p = 0.05 for men and r = 0.19; p less than 0.01 for women). Alcohol consumption was positively related to HDL cholesterol and triglycerides only among men (r = 0.19; p less than 0.001 and r = 0.12; p less than 0.05, respectively). Educational achievement was also positively related to HDL cholesterol in men (p less than 0.01) and women (p less than 0.001). Multivariate analyses indicate that the sex difference in LDL cholesterol was largely eliminated by controlling for body mass index while significant sex differences in both HDL cholesterol and triglycerides remained after controlling for covariates. Results suggest that the known associations in older adults of body mass index and health-related behavior with lipoproteins are well established by young adulthood. Early intervention particularly for obesity may help ameliorate some of the male excess in cardiovascular disease risk. PMID- 4025296 TI - Acute respiratory disease hospitalizations as a measure of impact of epidemic influenza. AB - Current measures of the health impact of epidemic influenza focus on analyses of death certificate data which may underestimate the true health effect. Previous investigations of influenza-related morbidity either have lacked virologic confirmation of influenza virus activity in the community or were not population based. Community virologic surveillance in Houston, Texas has demonstrated that influenza viruses have produced epidemics each year since 1974. This study examined the relationship of hospitalizations with acute respiratory disease to the occurrence of influenza epidemics. Discharge records of 13,297 acute respiratory disease hospitalizations that occurred between July 1978 and June 1981 were obtained from 11 hospitals with 48.4% of hospital beds available in Harris County (metropolitan Houston). The correlation of adult acute respiratory disease hospitalizations with established indices of community acute respiratory disease morbidity was strong (r = 0.74) and indicated that the peak of adult acute respiratory disease hospitalizations followed the peak of influenza virus isolations by one week. Only 23.2% of persons hospitalized were 65 years of age or older, compared to 60-70% of persons who die during influenza epidemics. Although the highest rates of acute respiratory disease hospitalizations occurred among infants and persons aged 65 years or older, the rates for adults 45-64 years and preschool children aged 1-4 years were greater than 1 per 1,000 persons. Surveillance of acute respiratory disease hospitalizations can improve the measurement of serious morbidity associated with epidemic influenza, and can better define the characteristics of persons at risk for development of illness requiring hospitalization. PMID- 4025297 TI - Problems in the use of dead controls in case-control studies. II. Effect of excluding certain causes of death. AB - A recent comparison of 493 dead and 697 living controls from a case-control study of cancer in the Minneapolis-St. Paul area showed that the dead controls of both sexes were reported to have been significantly heavier consumers of cigarettes, hard liquor, beer, and certain drugs, and to have had more adulthood diseases than living controls. The present analysis examines the effect of excluding causes of death associated with those exposures found in excess in the dead controls. Exclusion of individuals with smoking-related causes of death reduced but did not eliminate the excess of cigarette smokers among the dead controls. Deletion of individuals with alcohol-related causes of death only slightly reduced the excess among dead controls. Adjustment for cigarette smoking, however, nearly eliminated the association with alcohol consumption, particularly among males. For certain adulthood diseases and medications, the exclusion of individuals with exposure-associated causes of death also virtually eliminated the excesses found in the dead controls when compared with the living controls. Thus, it appears that even after extensive exclusion of smoking-related causes of death, the association between dead controls and cigarette smoking still remains, and the use of dead controls in case-control studies where cigarette smoking is the risk factor being evaluated may lead to a biased underestimated of risk. For the other exposures found in significant excess among the dead controls, the exclusion of exposure-related causes of death and proper adjustment for confounders may eliminate much or all of the excess. PMID- 4025298 TI - Confounding and misclassification. AB - The authors examine some recently proposed criteria for determining when to adjust for covariates related to misclassification, and show these criteria to be incorrect. In particular, they show that when misclassification is present, covariate control can sometimes increase net bias, even when the covariate would have been a confounder under perfect classification, and even if the covariate is a determinant of classification. Thus, bias due to misclassification cannot be adequately dealt with by the methods used for control of confounding. The examples presented also show that the "change-in-estimate" criterion for deciding whether to control a covariate can be systematically misleading when misclassification is present. These results demonstrate that it is necessary to consider the degree of misclassification when deciding whether to control a covariate. PMID- 4025299 TI - The MRFIT behavior pattern study. II. Type A behavior and incidence of coronary heart disease. AB - Behavior pattern was assessed by interview for 3,110 men at eight centers in the Multiple Risk Factor Intervention Trial (1973-1976). The Type A pattern was not significantly associated with risk of first major coronary events (coronary death and definite nonfatal myocardial infarction) after a mean follow-up of 7.1 years. Crude relative risks for Types A1-A2 versus X-B were 1.08 in usual care, 0.82 in special intervention, and 0.92 overall. Adjustment for age, blood pressure, cigarette smoking, serum cholesterol, consumption of alcohol, and educational attainment yielded relative risks of 0.99 in usual care, 0.81 in special intervention, and 0.87 overall (95% confidence interval = 0.59-1.28). The Jenkins Activity Survey Type A score, obtained for 12,772 men at all 22 centers, was also not significantly associated with risk of first major coronary events. Overall, crude risks in the lowest (Type B) through highest (Type A) quintiles of the score's distribution were 5.0%, 4.4%, 4.0%, 4.3%, and 4.1%, respectively. The proportional hazards regression coefficient, adjusted for the variables listed above, was -0.006 (95% confidence interval = -0.015-0.003). These results raise questions regarding the robustness of the Type A hypothesis in its present form. Further studies are needed to investigate these questions and to evaluate the validity of procedures used to assess behavior patterns. PMID- 4025300 TI - Breast cancer survival among Hawaii Japanese and Caucasian women. Ten-year rates and survival by place of birth. AB - Unlike past breast cancer survival comparisons between Japan and the United States, a recent study in Hawaii showed that Japanese women did not retain their survival advantage over Caucasian women after adjustment was made for stage at diagnosis. To test whether this finding in Hawaii was due to the limited duration of the follow-up (five years) or to the effects of migration, the survival experience of 1,357 Caucasian and 1,029 Japanese women with invasive breast carcinoma diagnosed in Hawaii between 1960 and 1979 was examined over a 10-year period as well as by place of birth. Multivariate adjustment by the proportional hazards regression model confirmed that the survival advantage of Japanese women in Hawaii is fully explained by their earlier stage of disease at diagnosis and suggested that, after recognition, the disease progresses at a similar pace in the two races. The survival comparison by place of birth revealed that second generation Hawaii Japanese women had better breast cancer survival rates than Japanese migrants from Japan, even after adjusting for stage, and that for Caucasian women, nativity was not associated with survival. These findings suggest that westernization, genetic constitution, or early life exposures cannot explain the overall or stage-adjusted breast cancer survival patterns observed among Caucasian and Japanese women in Hawaii. PMID- 4025301 TI - Overweight and changes in weight throughout adult life in breast cancer etiology. A case-control study. AB - Numerous epidemiologic studies have found body size to be a significant risk factor in the etiology of breast cancer. In an Israeli study population of 1,065 breast cancer patients, 964 surgical controls, and 981 neighborhood controls, height and weight at three periods (age 18, "most of adult life," and recent) were ascertained. The authors analyzed these parameters and body mass index (weight/height) for each period, as well as body mass index changes throughout life, controlling for age, menstrual status, and ethnic origin. Odds ratios were determined for three body mass index categories: 19.1-23, 23.1-27, and 27.1+, with a relative risk of 1 for body mass index less than or equal to 19. Their results show an increase in risk for breast cancer with greater recent body mass index among postmenopausal women aged 60+ (n = 461 for breast cancer, n = 414 for surgical controls, n = 401 for neighborhood controls). Crude odds ratios for the breast cancer/surgical control comparison are 1.23, 1.58, and 2.20, respectively, for each body mass index category; for the breast cancer/neighborhood control comparison 2.16, 2.44, and 2.99, respectively. Odds ratios adjusted for confounding factors (ages at menarche, first birth, and menopause; number of births; years of education; previous benign breast disease; and family history of breast cancer) are 1.17, 1.44, and 2.38, respectively (breast cancer/surgical control); and 1.78, 1.92, and 2.53, respectively (breast cancer/neighborhood control). Overweight does not emerge as a risk factor for breast cancer among premenopausal or younger postmenopausal women. Weight loss from most of adult life to recent weight appears to be protective, since mean loss in the 60+ age category is greater in both control groups than in breast cancer patients. In addition, breast cancer patients aged 60+ gained more weight during adult life than controls, and premenopausal breast cancer patients gained less weight than controls (for both comparisons, p less than or equal to 0.05, breast cancer vs. all controls combined. PMID- 4025302 TI - Comparison of glycosylated hemoglobin and fasting plasma glucose with two-hour post-load plasma glucose in the detection of diabetes mellitus. AB - In the course of a screening for diabetes mellitus in the Hotel-Dieu Hospital in Paris, from September 15, 1981 to April 1, 1984, an oral glucose tolerance test and a measurement of glycosylated hemoglobin were performed on 333 outpatients. With two-hour plasma glucose as a reference, the sensitivities of glycosylated hemoglobin, fasting plasma glucose, and a combination of glycosylated hemoglobin and fasting plasma glucose equal, respectively, 60.0%, 52.0%, and 40.0%; the specificities 90.9%, 98.7%, and 99.4%; the predictive value for a positive diagnosis 34.9%, 76.5%, and 83.3%. If one takes into account the implications of diabetes mellitus, especially its economic and psychosociologic consequences, it seems better for diagnosis--from a public health point of view--to use tests with a high degree of specificity and a high predictive value for a positive diagnosis, such as the combination of fasting plasma glucose and glycosylated hemoglobin, than tests with a good sensitivity but poor specificity. In the long term, validation of glycosylated hemoglobin as a diagnostic test for asymptomatic diabetes mellitus will be obtained only by reference to unquestionable criteria of the disease, determined by longitudinal survey. PMID- 4025303 TI - An inquiry into the epidemiology of melanoma. AB - The authors conducted a study of 404 melanoma patients and 521 control patients of both sexes at Roswell Park Memorial Institute. As have previous investigators, they found that higher risk attaches to upper socioeconomic status, as measured by occupation and education, lightness of complexion and hair, and amount of blue in the admixture of eye color. The authors also found a higher risk among individuals who reacted to sun exposure by burning, blistering, or freckling rather than by tanning. A particular concern was to measure risk associated with exposure to the sun. As have two other investigators, they found that risk decreased with increasing exposure, suggesting either that individuals continually exposed to the sun have less risk because of tanning, or that susceptibles purposely avoid sun exposure, or both. The fact that melanoma occurs with greater frequency on sites exposed to the sun suggests that sun exposure plays a part. These studies showed a dose-response increase in risk (odds ratios of up to 4 for males and over 6 for females) with increases in number of traits possessed, such as light complexion, and burning or freckling in response to sun exposure. This is consistent with the authors' earlier finding of a strong familial aggregation of melanoma. PMID- 4025304 TI - A comparison of three dietary methods for estimating vitamin A intake. AB - This study compared and evaluated vitamin A intake measured by three dietary methods (the 24-hour recall, the three-day food record, and a food frequency questionnaire) in 82 adult men enrolled in the Multiple Risk Factor Intervention Trial in Pittsburgh, Pennsylvania, during 1981. The dietary methods may be useful for group data, although differences were found: the food frequency questionnaire produced the highest mean daily estimate (7,876 +/- 569 IU) (mean +/- standard error), the 24-hour recall the intermediate daily estimate (6,944 +/- 602 IU), and the three-day food record the lowest daily estimate (5,137 +/- 470 IU). There was considerable variability between methods in individuals, suggesting that the intake of vitamin A estimated by one dietary method does not predict the intake estimated by another. At the individual level, a low significant correlation (rs = 0.28) occurred between the food frequency questionnaire and the three-day food record methods. Modest agreement in quartile ranking between these two methods indicated that 38% of the individuals fell into the same quartile, 73% into the same +/- one quartile, and 7% into opposite quartiles. PMID- 4025305 TI - The descriptive epidemiology of sudden infant deaths among natives and whites in Alaska. AB - From 1976-1980, the incidence of sudden infant deaths among native Alaskans was 2.9 times higher than that for white Alaskans (6.28 per 1,000 live births among natives vs. 2.14 per 1,000 live births among whites). Linked birth and death vital records data were used to compare the age-at-death distributions and relative risks associated with demographic factors for natives and whites. The purpose of the comparisons was to seek clues to the etiology of sudden infant death in natives. The age-at-death distributions for natives and whites were virtually identical (mean age at death 90.4 +/- 7.0 days for natives; 87.8 +/- 6.5 days for whites). The associations between the risk of sudden death and birth weight, marital status, season of birth, and residence were similar for natives and whites. The risk associated with young maternal age (less than 20 years) was significantly higher for whites than for natives (3.20 vs. 1.38). The sex ratio for sudden deaths among whites significantly favored males (relative risk = 1.78; female = reference); a significant sex ratio was not apparent for natives. Vital records data were useful for confirming the native-white difference in sudden infant death incidence, but not for elucidating etiologic differences between natives and whites. PMID- 4025306 TI - Geographic variation in declining ischemic heart disease mortality in the United States, 1968-1978. I. Rates and change, whites aged 35-74 years. AB - Despite the well known geographic pattern for heart disease mortality, studies of the decline in ischemic heart disease have not provided a comprehensive examination of its spatial component. In this study, the authors computed and mapped mean rates and per cent change in ischemic heart disease mortality for whites aged 35-74 years, for the period of the Eighth Revision (1968-1978) of the International Classification of Diseases. Visual evidence of clustering and markedly different spatial patterns were found for mean rate and per cent change among the state economic areas of the United States. PMID- 4025307 TI - Mortality of lead smelter workers. AB - To examine patterns of death in lead smelter workers, a retrospective analysis of mortality was conducted in a cohort of 1,987 males employed between 1940 and 1965 at a primary lead smelter in Idaho. Overall mortality was similar to that of the United States white male population (standardized mortality ratio (SMR) = 98). Excess mortality, however, was found from chronic renal disease (SMR = 192; confidence interval (CI) = 88-364), and the risk of death from renal disease increased with increasing duration of employment, such that after 20 years employment, the standardized mortality ratio reached 392 (CI = 107-1,004). Excess mortality was also noted for nonmalignant respiratory disease (SMR = 187, CI = 128-264). Eight of 32 deaths in this category were caused by silicosis; at least five workers who died of silicosis had been miners for a part of their lives. An additional 11 deaths resulted from tuberculosis (SMR = 139; CI = 69-249); in six of these cases, silicosis was a contributory cause of death. Cancer mortality was not increased overall (SMR = 95; CI = 78-114). An increase, however, was noted for deaths from kidney cancer (six cases; SMR = 204; CI = 75-444). Finally, excess mortality was noted for injuries (SMR = 138; CI = 104-179); 13 (23%) of the 56 deaths in this category were caused by mining injuries. The data from this study are consistent with previous reports of increased mortality from chronic renal disease in persons exposed occupationally to lead. PMID- 4025308 TI - Lung cancer mortality among men living near an arsenic-emitting smelter. AB - Etiologic factors for lung cancer were studied by the case-control technique among 636 men, including 212 with pulmonary carcinoma, who had died between 1961 and 1979 in a county in northern Sweden. Data on smoking habits, occupation, and residence were obtained from a next of kin to each study subject. Validation against data from other sources indicated that the exposure information was of high quality. A relative risk of 2.0 for lung cancer was seen among men who had lived within approximately 20 km from a large copper smelter. The increased risk, which is statistically significant (p less than 0.05), could not be explained by smoking habits or occupational background. Smelter workers and miners had relative risks for lung cancer of 3.0 and 4.1, respectively. No firm conclusions can be drawn on the cause of excess lung cancer risk in the smelter area, but it seems plausible that the very substantial emissions to air from the smelter, especially of arsenic, may have played a role. PMID- 4025309 TI - Foodborne streptococcal pharyngitis Kansas City, Missouri. AB - A foodborne outbreak of streptococcal pharyngitis occurred in association with a meeting of regional blood banking personnel held at a hotel in Kansas City, Missouri, on May 31-June 1, 1984. The incriminated meal was a salad buffet luncheon served on May 31. Of 106 persons identified as eating the luncheon, 60 (56.6 per cent) became ill. The most probable source of infection was an assortment of mousse desserts (p = 0.0532). PMID- 4025310 TI - Applications of microcomputer spreadsheet packages as adjuncts to multiple logistic regression analysis. AB - This paper illustrates how a microcomputer spreadsheet package can be used by epidemiologists to facilitate the computation of multiple logistic regression (MLR) probabilities, as well as odds ratios and associated confidence intervals, given the coefficients of the MLR model. By formatting a spreadsheet, data entry is greatly simplified, and computations are accomplished without any arithmetic manipulations on the part of the user. This approach makes it feasible for clerical support staff to assist in the computation of seemingly complex expressions. The increasing availability of microcomputers in clinical and research settings suggests that numerous analytic applications are amenable to this approach, thereby decreasing reliance on mainframe computers and desk-top calculators. PMID- 4025311 TI - Coffee consumption, benign breast disease, and breast cancer. PMID- 4025312 TI - Re: Mortality of widowed vs. married. PMID- 4025313 TI - Hematopoiesis and aging III: Anemia and a blunted erythropoietic response to hemorrhage in aged mice. AB - Whether the hematocrit normally declines in the aged or whether such a decline represents inapparent disease in addition to aging is a matter of dispute. Female B6D2f1 mice were studied at ages 3, 13, or 27-28 months, and there was no difference in hematocrit between the younger groups. The hematocrit of 45 aged mice was slightly lower than that of 66 younger mice; mean 43% vs 49% (p less than .001). However, rather unexpectedly, the total red cell mass was not decreased in the aged; rather, the plasma volume was expanded. Survival of mature red blood cells did not differ significantly between young and aged mice. Mice were bled 0.4 ml from the orbital sinus for 4 days, reducing the hematocrit of all groups to a nadir of 20-25%. Recovery of hematocrit began more slowly in aged than in young mice. That this reflected a difference in erythropoiesis rather than a difference in plasma volume equilibration was suggested by studies with 59Fe. 59Fe was given following the second bleed, and 1 day later RBC 59Fe was more than twice as high in young mice than in groups of aged mice. Aged mice that did not appear healthy had been excluded. Aged mice were divided into a group with significant amounts of gray hair and/or patches of hair loss and two groups with normal-appearing hair; the latter was subdivided into those weighing less (25-26 g) or more (30-34 g) than most aged mice. Neither hair condition nor weight influenced hematocrit or response to bleeding. These results suggest, but do not prove, that a mild "dilutional" anemia and a blunted erythropoietic response to hemorrhage may be an expected part of the murine aging process. PMID- 4025314 TI - Complications of heparin administration in normal individuals. AB - The incidence, severity, and pathogenic mechanism of heparin-associated thrombocytopenia with both bovine and porcine heparin administration were studied in forty normal males randomized to one of four treatment groups: beef lung heparin #1, beef lung heparin #2, porcine gut heparin, and saline control. All of the subjects receiving heparin developed a reversible increase in serum transaminases (SGOT, SGPT). However, other measurements of liver function were normal. Thirty-three percent of these heparinized normals had decreased platelet counts. The incidence of platelet count decrease was similar for both bovine and porcine heparins, but 4 of the 20 normals receiving bovine heparin had platelet counts less than 150,000/microliters. Immune pathogenesis was investigated by analyzing plasma from the volunteers for both platelet antibody and immune complexes. None of the men had increased platelet-associated IgG. Among the ten subjects with decreased platelet counts, IgG immune complexes were detected in three and C1q in seven. The heparin-associated thrombocytopenia appears not to be mediated by a platelet antibody. More probably it reflects a direct effect of the heparin on platelets. PMID- 4025315 TI - A case of factor V inhibitor. AB - A 57-year-old married Chinese male without a family history of bleeding disorder was presented with severe hemorrhagic tendency and was subsequently found to be suffering from an acquired inhibitor against coagulation factor V. The prolonged prothrombin time and activated partial thromboplastin time could not be corrected by the addition of normal plasma. Subnormal value of factor V level was noted accompanied with an abnormal platelet factor III availability test. With specific antisera and staphylococcal protein A, the inhibitor was characterized as an IgG(lambda) antibody. The hemorrhagic tendency and abnormal laboratory data were corrected after treating the patient with platelet concentrate transfusion and cyclophosphamide. PMID- 4025316 TI - Anti-Pr cold hemagglutination associated with livedo reticularis. AB - A report of anti-Pr cold hemagglutination associated with livedo reticularis is presented. Livedo reticularis is descriptive of the superficial venous system appearing when blood flow is altered in this area. Cold antibody directed against the Pr antigen of the red cell membrane can cause hemagglutination, thereby altering blood flow in cooler areas of the body. This patient had livedo reticularis approximately 8 months prior to detection of the anti-Pr cold agglutinin. PMID- 4025317 TI - Salmonella infection in hairy cell leukemia: report of a case. AB - A patient with hairy cell leukemia who developed mediastinal mass and fever is described. A CT-guided aspiration of the mass yielded Salmonella tiphymurium. Granulocyte response to infection was intact and could explain the favorable course of this unusual Salmonella infection. Although several reports deal with salmonellosis as a complication of immunodeficiency states, this type of infection is of rare occurrence in hairy cell leukemia. PMID- 4025318 TI - Irreversibly sickled erythrocytes in sickle cell anemia: a quantitative reappraisal. AB - Irreversibly sickled cells (ISCs), considered by some to be of major pathophysiologic significance, have been reported to comprise between 5-50% of the total red cell population in patients with homozygous sickle cell anemia. Since the deformation of erythrocytes containing sickle hemoglobin is highly dependent on the concentration of hemoglobin in the deoxy conformation, any method established to enumerate the true ISC count requires the hemoglobin to be in the full oxy or liganded conformation. Because the oxygen dissociation curve for sickle erythrocytes is significantly shifted to the right, extremely high partial pressures of oxygen are required to approach full saturation. On the other hand, fully liganding the hemoglobin in the oxy conformation with carbon monoxide (CO) can be readily accomplished. We found that there is a significant reduction in the average number of sickled forms in the peripheral blood of sickle cell anemia patients after incubation in CO (to a value of 6.5 +/- 3.5%) when compared to conventional methods for ISC preparations. These results suggest that fully liganded erythrocytes should be used in quantitating ISCs in studies of the pathophysiology of this disease, especially since ISCs are likely to affect rheology differently from reversibly sickling cells. PMID- 4025319 TI - Liver involvement in multiple myeloma. AB - One hundred twenty-eight records of patients with multiple myeloma were reviewed to assess the incidence and manifestations of liver involvement. Histologic study of the liver was available in 21 patients. Diffuse infiltration of the liver by plasma cells was observed in 10 patients, myeloid metaplasia in four, amyloidosis in two, toxic hepatitis in two, and extrahepatic cholestasis secondary to infiltration of the peripancreatic tissue by plasma cells in one. The clinical signs of plasma cell infiltration of the liver consisted of hepatomegaly in seven patients, mild elevation of liver enzymes in five, and portal hypertension in two. Jaundice was only observed in patients with hepatitis or extrahepatic cholestasis. Liver infiltration by plasma cells did not appear to have a major prognostic significance. PMID- 4025320 TI - Lymphocyte phenotype and function in chronically transfused children with sickle cell disease. AB - Immunologic studies were performed on mononuclear cells from ten chronically transfused children with sickle cell disease, and the results were compared with those from five other groups: 21 sickle cell patients who were not receiving regular transfusions, 6 chronically transfused children with other forms of refractory anemia, 10 previously splenectomized children, 5 boys with hemophilia A, and 27 normal adult controls. The helper:suppressor T cell ratios (T4:T8) in all groups except hemophiliacs were normal, were unrelated to the number of units transfused, and were not suggestive of findings reported for patients with the acquired immune deficiency syndrome (AIDS) or groups at risk for the syndrome. Percentages of T3, T4, and T8 cells were low in sickle cell and splenectomized patients, but not in chronically transfused patients with other anemias. Serum IgG was frequently elevated, and IgG synthesis in vitro was increased relative to IgM synthesis in sickle cell patients. Coculture experiments indicated that such findings may stem from a selective increase in IgG synthesis by B cells. Thus, transfused sickle cell patients have a particular pattern of immunologic abnormalities that is distinct from that seen in AIDS. PMID- 4025321 TI - Altered spectrin association and membrane fragility without abnormal spectrin heat sensitivity in a case of congenital hemolytic anemia. AB - In hereditary pyropoikilocytosis (HPP) and one type of hereditary elliptocytosis (HE), spectrin self-association is abnormal [5,7]. Spectrin extracted from normal erythrocyte membranes at 0 degree C is nearly all tetrameric, while in HPP and HE (type 1) a substantial amount of the extracted spectrin is dimeric. Abnormal reassociation of spectrin dimers to tetramers can also be demonstrated. We here report the case of a family in which the child has moderately severe hemolysis, with extreme microcytosis and poikilocytosis. The spectrin extracted at 0 degree C was predominately dimer. Parents had levels of dimer intermediate between patient and control values. The temperature dependence was normal for erythrocyte fragmentation; spectrin extractability; and circular dichroism of purified spectrin. Neither the patient nor either parent had elliptocytic red cells as judged from smears and scanning electron microscopy. The presence of substantial amounts of dimeric spectrin in the parents is consistent with a model in which each parent is heterozygous for a different nonassociating mutant spectrin, while the child has inherited a nonassociating molecule from each parent. In each individual, the degree of mechanical stability of the erythrocyte membrane, determined by ektacytometry, was proportional to the amount of tetramer found in the membrane. The description of this case is consistent with either HPP or a form of homozygous HE which is asymptomatic in the carrier state. PMID- 4025322 TI - Dyskeratosis congenita with hypoplastic anemia: a stem cell defect. AB - A case of dyskeratosis congenita (DC) with pancytopenia was studied in an attempt to elucidate the cause of the hypocellular bone marrow and pancytopenia. Levels of erythroid hemopoietic stem cells were estimated by clonal cell culture. Results showed a decrease in the number of precursor cells in both the bone marrow and the peripheral blood of this patient. PMID- 4025323 TI - More on biphenotypic leukemias and the 5q-syndrome. PMID- 4025324 TI - Fractional excretion of sodium as a guide to volume depletion during recovery from acute renal failure. AB - Fractional excretion of filtered sodium (FENa) is typically elevated (greater than 3%) in acute tubular necrosis and decreased (less than 1%) with volume depletion. We describe a patient who developed acute tubular necrosis with a FENa of 13%. Four weeks later, he was still oliguric but had also become volume depleted. FENa was 0.4% to 0.8%, considerably lower than FENa's measured in eight nonvolume-depleted patients in acute renal failure. Vigorous intravenous fluid therapy in this patient produced a prompt increase in urine volume and improvement in renal function. We conclude the following: (1) a marked decrease in FENa in a patient with acute tubular necrosis should suggest the development of a superimposed sodium-retaining state such as volume depletion, and (2) severe volume depletion may delay or mask recovery from acute tubular necrosis. PMID- 4025325 TI - Renal involvement in visceral leishmaniasis. AB - In a prospective study of 50 patients with visceral leishmaniasis, laboratory abnormalities suggestive of renal involvement were not infrequent. Proteinuria and/or microscopic hematuria or pyuria were observed in 51% of such cases. Twenty four hour urinary protein excretion was elevated in 57% of patients in all cases below 1g/24 hours. An abnormal acid-load test was demonstrated in 12 of 18 patients studied before therapy of the parasitic infection with N-methyl glucamine. Of interest was the demonstration of tubulo-interstitial involvement in the renal histology of all seven patients studied; also, in five of seven patients there was a proliferative glomerulonephritis, usually mild, on histologic examination. In general, there was a tendency to subsidence of abnormal laboratory findings within one month after specific therapy. Renal involvement in visceral leishmaniasis was mild and seemed to revert with the cure of the leishmanial infection. PMID- 4025326 TI - Statement on the release of ibuprofen as an over-the-counter medicine. Ad Hoc Committee for the National Kidney Foundation. PMID- 4025327 TI - Hemodynamic effects of lysine-vasopressin in orthostatic hypotension. AB - Previous investigations have demonstrated that the postural stimulation of arginine vasopressin (AVP) release is reduced in patients with Shy-Drager syndrome. We studied the effects of lypressin nasal spray on hemodynamic parameters in ten patients with chronic orthostatic hypotension. Heart rate, blood pressure, and stroke volume were measured at 0 degrees, 45 degrees and 70 degrees tilt before and one-half hour after two nasal sprays (four United States Pharmacopeia posterior pituitary pressor units, 7.4 micrograms) of lypressin. Lypressin did not significantly alter the effect of tilt on heart rate, stroke volume, and cardiac output but increased the blood pressure and total peripheral resistance. AVP analogues should be tested for treating chronic postural hypotension. PMID- 4025329 TI - Complete distal renal tubular acidosis in systemic lupus: clinical and laboratory findings. AB - We report two patients with systemic lupus erythematosus (SLE) who were found to have complete (acidotic) distal renal tubular acidosis (DRTA). One patient had nephrocalcinosis and renal magnesium wasting with tetany; the other patient had nephrolithiasis and nephrotic syndrome secondary to membranous glomerulopathy. Both patients had decreased urinary citrate excretion but neither had hypercalciuria. We discuss the association of DRTA with immunologic disorders and the possible role of hypocitraturia in promoting renal calcification in these patients. We suggest that patients with renal calcification be evaluated for DRTA, and that patients found to have DRTA be further evaluated for signs, symptoms, and laboratory evidence of immunologic disorders. PMID- 4025328 TI - Evaluation of a flushing solution designed to protect kidneys from in situ ischemia. AB - An in situ flushing solution was evaluated with regard to the following: (1) its ability to protect the kidney during 60, 90, and 120 minutes of normothermic ischemia; (2) the effects of using an intracellular versus extracellular electrolyte composition in the flushing solution; and (3) the ability of the flushing solution to complement in situ hypothermia as a protective measure during long-term ischemia. Rat kidneys were briefly flushed in situ with an isotonic phosphate buffered solution (pH 7.2) containing 50 milliosmole of sucrose. The left renal pedicle was then immediately clamped to render the kidney ischemic and to hold the flushing solution in the kidney. Following removal of the pedicle clamp, a contralateral nephrectomy of the right kidney was performed and daily serum creatinine levels determined to evaluate postischemic renal function. The results indicate the following: (1) the flushing procedure is very effective in preventing postischemic acute renal failure following 60 minutes of normothermic ischemia, but is considerably less effective for ischemic times of 90 minutes or more; (2) an intracellular electrolyte composition in the flushing solution does not improve the protective effects of this solution; and (3) the flushing procedure can significantly improve on the protection otherwise provided by in situ hypothermia. PMID- 4025330 TI - Bromocriptine and the hypothalamic hypophyseal function in patients with chronic renal failure on chronic hemodialysis. AB - Ten patients with chronic renal failure on chronic hemodialysis had the following tests to evaluate the integrity of the hypothalamic hypophyseal axis: (A) glucose tolerance test, (B) thyrotropin releasing hormone stimulation test, (C) clonidine stimulation test, (D) insulin induced hypoglycemia, and (E) LH/RH stimulation test. The majority of those tests were abnormal and prolactin values were found to be moderately elevated in all the patients. Bromocriptine (1.25 mg twice a day) was given to all the patients for 1 month and then, while on bromocriptine, the tests were repeated. Although there is a decrement in the concentration of serum prolactin level, none of the hypothalamic hypophyseal abnormalities were corrected. However, five of the ten patients reported an improvement of their impotence with bromocriptine. The patients who responded had high levels of FSH and LH with levels of testosterone above 1 mg/mL. The nonresponders had low FSH and LH levels and very low testosterone levels. Therefore, bromocriptine, although possibly beneficial in some dialysis patients, is not a drug that can normalize abnormal functioning of hormones in the dialysis population. PMID- 4025331 TI - Effective use of streptokinase for peritoneal catheter failure. AB - The fibrinolytic enzyme streptokinase (streptase) was infused into the peritoneal catheter in 19 episodes of catheter failure in 16 patients. Intraabdominal bleeding prior to infusion was seen in seven of these episodes. Fibrin strands and clots were present in four additional successful cases. Streptokinase successfully relieved the obstruction in 13 episodes in 11 patients. The procedure failed in two cases of omental ingrowth and in another with catheter malposition. Streptokinase infusion also failed in two patients with Pseudomonas aeruginosa and one patient with Staphylococcus epidermidis peritonitis. Intraperitoneal streptokinase infusion is simple and free of side effects. Its use should be considered in peritoneal catheter failure, particularly in cases where bleeding or fibrin accumulation may play a role. PMID- 4025332 TI - Tenckhoff catheter obstruction resulting from invasion by Curvularia lunata in the absence of peritonitis. AB - A 60-year-old black woman on continuous ambulatory peritoneal dialysis (CAPD) presented with Tenckhoff catheter malfunction. She exhibited no signs or symptoms of acute peritonitis. Darkly pigmented plaques were adherent to the inner wall of the catheter and exchange tubing focally throughout its length. Similar material was adherent to the protein coagulum in the dialysis bag. The Tenckhoff catheter and tubing were removed, and hemodialysis was initiated. Cultures of the catheter and the dialysate protein coagulum grew the saprophytic soil fungus, Curvularia lunata. Histologic examination of the catheter and tubing demonstrated penetration of each by hyphae. Catheter removal alone was sufficient to eradicate the fungus since recurrence of colonization or peritonitis has not occurred following the resumption of CAPD. Peritonitis produced by opportunistic pathogens especially fungi is increasingly common. Although Curvularia species have been implicated in pulmonary and cerebral mycetomas, allergic bronchoalveolar disease, and keratitis, they have not been reported previously to cause peritonitis or catheter malfunction in CAPD patients. Fungal invasion of CAPD catheters can produce mechanical obstruction even in the absence of peritonitis. Such colonization does not preclude resumption of chronic peritoneal dialysis at a later date. PMID- 4025333 TI - Spontaneous remission of nephrotic syndrome in IgA glomerular disease. AB - We report two cases of adult onset nephrotic syndrome with pathologic features of minimal change disease but a predominance of IgA in mesangial regions. Both cases underwent spontaneous remission despite an episode of recurrent nephrotic syndrome in one patient. The relationship of the glomerular disease to minimal change and IgA nephritis is discussed. PMID- 4025335 TI - Health effects studies of exposure from hazardous waste sites--where are we today? PMID- 4025337 TI - The middling tendency in reading chest films for pneumoconiosis: an important source of bias and variability. AB - The tendency for readers of chest films of the pneumoconioses to place films in the middle of the International Labour Office (ILO) categories of profusion (eg, 1/1, 2/2) was described by Morgan et al [1974], who saw this tendency as a possible source of bias. The present study reexamines the middling tendency in relation to bias and variability by comparing duplicate readings of chest films for pneumoconiosis. Readings of trained lay persons were compared to professional readings of the same films and readings of professional readers were compared with each other. Reasons for the middling tendency, which include the use of standard middle films and the instructions given to users of the classification, are suggested and possible solutions are proposed. PMID- 4025336 TI - A longitudinal study of pulmonary function in coal miners in Lorraine, France. AB - A longitudinal study of pulmonary function and radiological change has been conducted on 141 nonsmoking coal miners and 256 smoking coal miners from Lorraine, France. At the time of the first examination occasioned by radiological change or shortness of breath, the men averaged between 46.6 years and 50.9 years of age, and they retired approximately 8 years after entering the study. They have been followed for average periods of about 18 years and a mean of five FEV1 observations per man were made over that period. Changes in radiological category have been documented. Average rates of decline of FVC and FEV1 were similar, and varied between -47 ml/yr in nonsmoking miners still alive, to -78 ml/yr in deceased smoking miners. These accelerated rates were similar before and after retirement from the mine. PMID- 4025338 TI - Gallium-67 citrate imaging in underground coal miners. AB - Twenty-two underground coal workers with 27 or more years of coal dust exposure were studied with gallium-67 citrate (Ga-67) imaging. Radiographic evidence of coal workers pneumoconiosis (CWP) was present in 12 subjects. The Ga-67 scan was abnormal in 11 of 12 with, and 9 of 10 without, CWP. The Ga-67 uptake index was significantly correlated with total dust exposure (p less than 0.01) and approached significant correlation with the radiographic profusion of the nodules (0.10 greater than p greater than 0.05). There was no correlation between Ga-67 uptake and spirometric function, which was normal in this group of patients; furthermore, increased lung uptake of gallium did not indicate a poor prognosis in subjects no longer exposed to coal dust. While coal dust exposure may be associated with positive Ga-67 lung scan in coal miners with many years of coal dust exposure, the scan provided no information not already available from a careful exposure history and a chest radiograph. Since Ga-67 scanning is a relatively expensive procedure we would recommend that its use in subjects with asymptomatic CWP be limited to an investigative role and not be made part of a routine evaluation. PMID- 4025339 TI - A proportional mortality study of the acting profession. AB - Proportional mortality of actors and actresses was studied because cancers of many sites have been linked to hair dyes and cosmetics of which actors have been frequent users. Death records (1950-1978) for 2,618 white male and 838 white female members of Actors Equity and the Screen Actors Guild were compared with the U.S. mortality rats. Among males, significantly elevated proportional mortality ratios (PMR) were found for suicide (1.58), cirrhosis of the liver (1.99), all malignancies (1.15), and cancers of the colon/rectum (1.32), pancreas (1.51), and testes (2.37). Colon/rectum and pancreas cancers were not significantly elevated by proportional cancer mortality. Among females, significantly elevated PMRs were found for suicide (2.02) and lung cancer (2.20). Suicide in either sex was much more common in California than in New York. The elevated lung cancer in females was confined to Equity members. No elevations were found for cancers that have been related to hair dye or cosmetic use--ie, breast, ovary, bladder, leukemia, and lymphomas. PMID- 4025340 TI - Concentration of ethylene oxide in the alveolar air of occupationally exposed workers. AB - Ethylene oxide was tested in environmental air and in the alveolar air of 10 workers employed in a hospital sterilizer unit at hourly intervals during the work shift. Alveolar ethylene oxide concentrations (Ca) were correlated with environmental concentration (Ci) in all the workers studied (r = 0.89-0.99). The ratio between alveolar and environmental concentration (Ca/Ci) given by the slope of the regression line obtained for all the data collected was 0.24. This means that the alveolar retention of ethylene oxide, expressed as 1 - (Ca/Ci), corresponded, on average, to about 75% of the environmental concentration. PMID- 4025341 TI - Proportionate mortality study of workers in the garment industry exposed to formaldehyde. PMID- 4025342 TI - Benzene as a leukemogenic and carcinogenic agent. AB - Today there seems to be sufficient data to incriminate benzene as a potent carcinogenic agent causing leukemia, malignant lymphoma, multiple myeloma and lung cancer, as well as numerous disorders of the bone marrow depression. Other factors (such as genetic and individual susceptibility) may have a role in the development of these different types of malignancies and hematologic disorders. In this paper, data concerning all these problems are presented and discussed. PMID- 4025343 TI - Freezing and rapid thawing of antibiotic mixtures. PMID- 4025344 TI - Using graphics printers for prescription labels. PMID- 4025345 TI - Multifaceted orientation of house staff to pharmacy operations. PMID- 4025346 TI - Facilitating aseptic mixing of sterile substances. PMID- 4025347 TI - Reducing the costs of cephalosporin therapy. PMID- 4025348 TI - Monetary incentive for pharmacists to control drug costs. AB - An incentive program that paid hospital pharmacists at United Hospitals Incorporated (UHI) and Children's Hospital Incorporated (CHI) a percentage of the money saved by the pharmacy on drug and i.v. expenses in 1984 is described. Hospital administration, as part of a hospitalwide incentive program, approved the pharmacy department's proposal for a monetary incentive program. Pharmacy managers hoped that, by rewarding all pharmacists for their efforts to control costs, they could potentiate other cost-containment programs (stronger formulary control and improved purchasing and inventory control) and improve clinical services while maintaining quality of care. The incentive calculation was derived from the percentage of expenses saved on drugs and i.v. solutions and sets relative to budget. The payout, to be applied to 1984 salaries of pharmacists, could not exceed 10% of salary or more than 35% of the total savings to the hospital. A screening mechanism was established to protect the hospital from paying an incentive if the total pharmacy expenses exceeded budget. In fiscal 1984, drug and i.v. expenses per adjusted case decreased 1.55%, which led to each full-time pharmacist receiving an average payout of $500. This payout was less than had been anticipated because of a nursing strike at other hospitals, which resulted in an influx of intensive-care patients. The monetary incentive program for pharmacists is a useful tool for controlling drug and i.v. expenses and for rewarding pharmacists for successful cost-saving approaches. PMID- 4025349 TI - Bid purchasing of radiopharmaceuticals and radiopaque contrast media. AB - Use of product standardization and competitive-bid purchasing for radiopharmaceuticals and radiopaque contrast media in a 1000-bed teaching hospital is described. The hospital's use of radiopharmaceuticals was reviewed, and all agents were listed with their product specifications and order quantity or frequency. Manufacturers and wholesalers were asked to submit unit prices for each of their products. Similar procedures were followed for radiopaque contrast media; wholesalers and manufacturers were asked to submit unit prices that would be guaranteed for a 12-month contract period. A nuclear pharmacist and radiologists reviewed the submitted bids and awarded contracts, basing their decisions primarily on product acceptability and selection criteria and then on relative costs of the agents. Annual costs were reduced 16% ($16,500) for radiopharmaceuticals and 21.3% ($66,500) for radiopaque contrast media. The program also resulted in decreased inventory of radiopaque contrast media and in faster and less expensive acquisition of emergency orders. Working with the radiology department to compile a standard list of radiopharmaceuticals and radiopaque contrast media and soliciting competitive bids by vendors of these products resulted in annual savings of more than $83,000. PMID- 4025350 TI - Evaluating a restrictive formulary system by assessing nonformulary-drug requests. AB - Nonformulary-drug requests were used to evaluate a restrictive formulary system in a large university hospital, and a telephone survey of eight similar hospitals was conducted to assess the restrictiveness of their formulary systems. Nonformulary-drug requests were evaluated by two drug information pharmacists over a 12-month period (January-December 1984) to assess the frequency with which nonformulary items were ordered, the costs associated with the procurement of nonformulary drug products, and the rationales given by physicians when ordering nonformulary products. Of all nonformulary requests, 65% were for drugs previously evaluated by the pharmacy and therapeutics committee and denied admission to the formulary. A cost savings of $1887 would have resulted if formulary alternates had been used instead of nonformulary products. Excluding 22% of nonformulary items that were requested for the continuation of preadmission drug therapy, only 13% of the rationales for the remaining requests were appropriate. Although the eight other hospitals surveyed said they had restrictive formularies, all had frequent requests and procedures for procuring nonformulary items and some formularies included most available drugs. The formulary system at the study hospital was considered restrictive, but procedures for nonformulary-drug requests limited the effectiveness of the system. If any benefit is to result from formulary systems, hospitals must strengthen their enforcement of formulary restrictions. PMID- 4025351 TI - Use of serum drug concentrations in outpatient clinics. AB - A four-month retrospective study was conducted to analyze the use of serum drug concentrations (SDCs) in the outpatient clinics of a teaching hospital. The general internal medicine, asthma and allergy, cardiology, and neurology clinics were selected as frequent users of SDCs. Serum theophylline, digoxin, quinidine, procainamide, carbamazepine, phenytoin, and phenobarbital concentrations obtained during patient clinic visits were audited by trained pharmacy students using medical records and computer-generated laboratory data. The SDCs were evaluated for (1) the appropriateness of how they were obtained, (2) the appropriateness of the actions taken on the results, (3) the reasons they were ordered, and (4) the patient charges secondary to obtaining SDCs incorrectly or taking inappropriate actions on the results. Overall, the SDCs from all the clinics combined were obtained appropriately 251 (61.4%) of 409 times. Appropriate actions were taken on the SDC results 82.4% of the time. A change in therapy was made after an SDC was ordered 24.4% of the time. A total of $4975 of patient charges was associated with incorrectly obtained SDCs or inappropriate actions taken on SDC results. The asthma and allergy clinic, which was staffed by a clinical pharmacist, used SDCs more appropriately than the other clinics. Pharmacists or other professionals should be used to obtain accurate SDC information and to follow-up on SDC results to maximize drug therapy and reduce costs. PMID- 4025352 TI - Potential drug interactions in surgical patients. AB - The incidence and frequency of potentially serious drug interactions were evaluated in hospitalized surgical patients. Drug profiles of patients on the general surgical service of a tertiary-care teaching hospital were retrospectively reviewed for two six-month periods to determine how often drugs that are known for major interactions were prescribed concurrently. Interactions were studied that were relatively well documented and potentially harmful to the patients. A total of 1825 patient profiles were reviewed (21,888 patient days). At least one potential drug interaction was found in 17% of the patients. Interactions were found to occur at the rate of 1 for every 59 patient days. Digoxin and cimetidine were the potential interacting drugs in almost 90% of the cases. Hospitalized surgical patients require close monitoring because they frequently receive potentially interacting drugs. PMID- 4025353 TI - Survey of consumer users of a statewide drug information service. AB - A survey of consumers who had used a state-supported drug information center (DIC) was conducted to determine reasons for and frequency of use of the DIC and opinions about the services of the DIC. The Arizona Poison and Drug Information Center (APDIC) mailed questionnaires to 281 lay persons who had requested information about use of prescription or nonprescription drugs. The questionnaires were sent only to callers who responded affirmatively when asked to participate in the survey. Of 154 (54.8%) respondents (83.8% women), 40.9% were using no prescription drugs at the time of the survey and 83.8% purchased fewer than two nonprescription drugs per month. Approximately 44% said they tried to obtain drug information at least once per month. Pharmacists were named as the most frequent source of drug information for nonprescription drugs, but information about prescription drugs was sought more frequently from physicians and reference books. APDIC was mentioned most frequently as a source of information about all drugs (both prescription and nonprescription). Nearly all respondents said the information from APDIC was helpful and the service should be continued. Drug information consumers looked to this DIC to meet a demand not being met by pharmacists or physicians in the community. Consumers viewed the information as valuable and used this service because it was available and accessible. PMID- 4025354 TI - Clinical pharmacy services in Florida hospitals--1984. AB - To ascertain the progress made in the implementation of clinical services in Florida hospitals, a survey conducted in 1977 was readministered in 1984. Questionnaires were sent to the directors of pharmaceutical services of all 256 Florida hospitals. Nine questions on clinical services were identical to the 1977 survey and two additional questions were included on nutritional support services and pharmacokinetic dosing consultations. The directors were also asked if they had conducted studies to document the cost-effectiveness of their clinical pharmacy services. Questionnaires were returned by 75% of the directors. As in the 1977 survey, approximately half of the hospitals had less than 200 beds. Slightly more than 82% of the hospitals had total unit dose systems and about 7% had partial systems, which was considerably higher than the 58% with either total or partial systems found in the 1977 survey. Services such as patient monitoring, inservice education, and drug-use review were being offered substantially more than in 1977. Conducting patient medication histories, attending rounds with physicians, and providing discharge consultations were the least-performed clinical services. The reasons given for not implementing these services were similar in both surveys. However, while the lack of adequately trained pharmacists was frequently cited in 1977, very few respondents cited it as an obstacle in 1984. Several respondents indicated that they had documented cost savings attributable to their clinical pharmacy services. Clinical pharmacy programs are continuing to grow in Florida hospitals; however, pharmacy administrators appear to be having some of the same problems implementing these services as they did previously. PMID- 4025355 TI - Drugman--a computerized supplement to a hospital's drug information newsletter. AB - A computerized supplement to a hospital's drug information newsletter, called Drugman, is described. The pharmacy department of a 452-bed teaching hospital developed Drugman. The program uses the "Converse" software, which was developed by the hospital's computer medicine department. The program provides information on new drugs recently added to the formulary and updated information on current formulary drugs. It also provides information on investigational drugs. A staff pharmacist is responsible for coordinating the writing and review of each new drug monograph in the system, as well as the computer entry and up-dating of existing monographs. The program is available to all medical, nursing, and pharmacy personnel via computer terminals located on each nursing unit and in the pharmacy department. Survey questions at the end of the program elicit user response to the program and suggestions for additions or changes. In the initial 14-month period, the general response to Drugman has been favorable. Drugman represents a new method of disseminating drug information via computer in an individual hospital. The program complements traditional drug information sources and has been received positively in our hospital. PMID- 4025356 TI - Simple stability-indicating assay for histamine solutions. AB - A chemical stability-indicating assay for the routine analysis of histamine in isotonic-phosphate buffer solutions was developed and evaluated. A quantitative colorimetric assay was developed by adapting the Pauly reaction specific for the imidazole group for the determination of histamine in buffer solutions. Stock solutions of histamine diphosphate 1 mg/mL were diluted with isotonic phosphate buffer to produce standards for an imidazole-group assay and for the USP assay method based on the Folin reaction of free amino groups. The specificity of the assays was evaluated by subjecting samples to ultraviolet irradiation and heat for various time periods and then analyzing for histamine content. Both of the colorimetric assays provided reproducible linear calibration curves passing through the origin for histamine diphosphate concentrations. For the Pauly reaction assay, the average coefficients of variation between and within runs were 0.5% and 0.1%, respectively. The assay had recoveries of 100.6% and 100.8% at 8 and 25 micrograms/mL of histamine diphosphate concentrations, respectively, and a sensitivity of 3 micrograms/mL. Based on the results of the Pauly-reaction assay, irradiation caused decreases in the apparent concentrations as large as 69.2% depending on the duration of the irradiation and distance from the light source. When the histamine diphosphate solutions were stored in the dark at 60 degrees C for five days, a decrease of only 6.3% occurred. Based on the results of the Folin-reaction assay, irradiation caused increases in the apparent concentrations as large as 50.6%. The Pauly colorimetric assay based on the imidazole group appears to be more appropriate for histamine solutions than the amino-group assay based on the Folin reaction. PMID- 4025357 TI - Robinson-Patman update: De Modena v. Kaiser Foundation Health Plan. AB - The findings in a case dealing with price differentials for drugs purchased for members of a health maintenance organization (HMO) are presented. In the case of De Modena v. Kaiser Foundation Health Plan, community pharmacists in California and Oregon claimed that sales of drugs purchased at special prices by Kaiser Permanente Medical Care Program for its members constituted price discrimination as interpreted by the United States Supreme Court decision in Abbott Laboratories et al. v. Portland Retail Druggists Association, Inc. A United States Court of Appeals ruled in favor of Kaiser, holding that the HMO was purchasing drugs for its "own use" and thus qualified for exemption from the provisions of the Robinson-Patman Antidiscrimination Act. The implications of this decision are discussed in light of corporate restructuring and diversification of services by hospitals. Evaluation of the overall health-care mission of a health-care organization rather than strict application of the Portland decision may be used to identify permissible uses of drugs purchased at special prices by these organizations. PMID- 4025358 TI - Reducing drug expenditures in a small hospital. PMID- 4025359 TI - Cephalosporin use and restriction in pediatric hospitals. PMID- 4025361 TI - ASHP statement on third-party compensation for clinical services by pharmacists. PMID- 4025360 TI - Particle formation of third-generation cephalosporin injections. PMID- 4025362 TI - ASHP guidelines for implementing and obtaining compensation for clinical services by pharmacists. PMID- 4025363 TI - ASHP technical assistance bulletin on assessing cost-containment strategies for institutional pharmacies. PMID- 4025364 TI - Aminoglycoside resistance in gram-negative bacilli during increased amikacin use. Comparison of experience in 14 United States hospitals with experience in the Minneapolis Veterans Administration Medical Center. AB - Resistance to amikacin, gentamicin, and tobramycin was surveyed prospectively during controlled aminoglycoside usage in 14 hospitals. Following an initial baseline period (minimum, three months) during which gentamicin use predominated, gentamicin and tobramycin were placed on restrictive control, establishing amikacin as the aminoglycoside of general use (86 percent of total aminoglycoside usage). During an average of 35 months' restriction of gentamicin and tobramycin, significant reductions in gram-negative resistance to gentamicin (8.4 to 7.0 percent, p less than 0.001) and tobramycin (6.0 to 5.3 percent, p less than 0.01) were observed. The most significant decreases in resistance to gentamicin and tobramycin (p less than 0.001) were found for Pseudomonas aeruginosa, Klebsiella species, Serratia species, and Proteus species. Amikacin resistance among gram negative bacilli was observed to increase marginally from 1.4 to 1.7 percent (p less than 0.05) during the surveillance period, primarily due to a significant increase in resistance among P. aeruginosa (3.0 to 3.9 percent, p = 0.05). These data were compared with data from a similar surveillance program at the 700-bed Minneapolis Veterans Administration Medical Center. Over a period of 54 months, both gentamicin and tobramycin resistance decreased significantly when amikacin was used (p less than 0.001), then increased with reintroduction of gentamicin (p less than 0.05), and decreased significantly with reintroduction of amikacin (p less than 0.001). Despite predominant amikacin use for a total of 38 months, amikacin resistance did not increase and actually decreased significantly (p less than 0.05) in the last 12 months. PMID- 4025365 TI - Role of aminoglycosides as first-line therapy in multiple clinical settings. Proceedings of a symposium. February 1-2, 1985. Palm Springs, California. PMID- 4025366 TI - Use of aminoglycosides in immunocompromised patients. AB - For much of the last decade, combination therapy with aminoglycosides has been accepted as the therapeutic approach of choice in immunocompromised hosts. Improved clinical results have also correlated with the presence of synergistic interactions between the aminoglycoside and beta-lactam components of a regimen. Differences between the aminoglycosides and beta-lactam agents remain a subject of controversy. Studies at the University of California, Los Angeles, Medical Center suggest that amikacin interacts more frequently in a synergistic manner with beta-lactams than do alternative aminoglycosides. Amikacin has been used experimentally and (following licensure) without reservation at the University of California, Los Angeles, Medical Center since 1973. Almost 100 blood isolates of both Pseudomonas aeruginosa and Klebsiella pneumoniae collected during the last 12 years have been retested, and no evidence of increased aminoglycoside resistance was found. A relatively new development is interest in empiric therapeutic regimens that employ two beta-lactam agents. In a large, recently completed study, less satisfactory results were observed in P. aeruginosa infections treated with the "double beta-lactam" than in those treated with the regimen containing amikacin; furthermore, nephrotoxicity and eighth nerve damage occurred no more commonly in the group receiving amikacin than in recipients of the double beta-lactam regimen. PMID- 4025368 TI - Antibiotic treatment of complicated urologic infections. Six selected case studies. AB - The use of aminoglycosides in urology is limited primarily either to preoperative prophylaxis or to acutely ill patients. Frequently in this latter group, there is little margin for error, and the appropriate drug(s) must be given at the outset. In addition to receiving antibiotics, patients in distress should be resuscitated with fluids, evaluated to determine the cause of their sepsis, and promptly and definitively treated. It is important early in the course of therapy to drain the site of obstruction or abscess, remove foreign bodies, or debride necrotic areas if medical measures are to be successful. The rationale for selection of an aminoglycoside and treatment in these patients is discussed, using six case studies as illustrations. PMID- 4025367 TI - Treatment of pediatric infections with amikacin as first-line aminoglycoside. AB - Because of increased aminoglycoside resistance of hospital bacterial isolates, aminoglycoside sensitivity patterns of isolates in a large children's hospital were assessed before and during a 33-month period of almost exclusive amikacin use. There was no significant change in overall resistance rates of gram-negative enteric bacteria to gentamicin (4.8 percent and 4.6 percent), tobramycin (2.5 percent and 3.6 percent), and amikacin (1.2 percent and 1.8 percent) from the pre amikacin period to the amikacin usage period, respectively. No significant differences were observed for isolates of Escherichia coli, Klebsiella, Serratia, Acinetobacter, and Pseudomonas species. In contrast, significant decreases in gentamicin and tobramycin resistance rates for Enterobacter, Citrobacter, and Pseudomonas aeruginosa and in gentamicin resistance of Proteus were found. Very little change in resistance of staphylococcal isolates was seen during a shorter evaluation period. Pediatric aminoglycoside usage includes therapy of neonatal infections, cystic fibrosis, febrile neutropenic episodes in patients with cancer, abdominal surgery, bacterial endocarditis, and gram-negative central nervous system infections. Amikacin has also been used successfully as single dose therapy of urinary tract infections, and acceptable cerebrospinal fluid levels of amikacin have been documented in hydrocephalic patients with ventriculitis. In vitro studies of 22 bacterial isolates demonstrated synergy between amikacin and penicillin or newer cephalosporins in 13, an additive effect in seven and indifference in two. No antagonism was found. In addition, in vivo synergy between imipenem and amikacin was found in neutropenic infant rats with P. aeruginosa sepsis using a strain with which no synergy was demonstrable in vitro. Amikacin is effective in pediatric infections and is well tolerated by children. Because excessive or inadequate levels are frequent with usually recommended doses, particularly in neonates and patients with compromised renal function or cystic fibrosis, serum levels should be monitored to minimize risk and to ensure therapeutic levels. PMID- 4025369 TI - Pneumonia caused by gram-negative bacilli. AB - Gram-negative bacillary pneumonia has become an increasingly important disease in immunosuppressed, elderly, and hospitalized patients. The clinical features, etiologic agents, population at risk, treatment, and outcome in patients with well-documented gram-negative pneumonia were compared in two groups of patients: those with bacteremic pneumonia and those with nonbacteremic pneumonia documented by transtracheal aspiration. Clinical features were frequently subtle in both groups. A wide range of gram-negative bacilli were implicated as pathogens and pneumonias documented by transtracheal aspiration were frequently mixed infections. Pseudomonas aeruginosa and Serratia marcescens were the most common pathogens causing bacteremic pneumonias, whereas Escherichia coli and Klebsiella were more common in the nonbacteremic group. Gram-negative bacillary pneumonia was frequently a lethal disease despite two-drug therapy, particularly in bacteremic patients. PMID- 4025370 TI - Identification and treatment of infections in multiply traumatized patients. AB - Trauma is the leading cause of death among young adults, and infection is a leading complication in multiply traumatized patients. All antibiotic use and all infections among 1,009 patients admitted to the Maryland Institute for Emergency Medical Services Systems over a six-month period were reviewed. The vast majority of patients had sustained high-speed automobile trauma and had blunt injuries. All antibiotics were given by the infectious diseases consultants under predetermined protocols. During this time period, 175 infections and 76 bacteremias were identified. Thirty-three percent of the antibiotic use was for prophylaxis. Prophylactic antibiotics were used for open fractures, in which a cephalosporin was used; for abdominal trauma, in which an aminoglycoside and clindamycin or cefoxitin alone was used; and for penetrating open fractures of the oral cavity, in which penicillin was used. As therapy, the aminoglycosides were used in 25 percent, the cephalosporins in 21 percent, the penicillins in 39 percent, and other antibiotics in 15 percent of the cases. The organisms identified as causing infection were Staphylococcus aureus (25 percent), Escherichia coli (18 percent), Enterobacter species (17 percent), Pseudomonas species (12 percent), and Klebsiella species (11 percent). The sites of infections were primary bacteremia (11 percent), vascular lines (21 percent), the central nervous system (3 percent), the lower respiratory tract (13 percent), the paranasal sinuses (6 percent), the urinary tract (19 percent), surgical wounds (11 percent), the abdomen (7 percent), and other sites (9 percent). More than 82 percent of the infections that occurred were nosocomial in origin and were related to the various procedures used for monitoring and therapy in these critically ill patients. Infections of the abdominal cavity and the lower respiratory tract accounted for eight of the 10 infection-related deaths in these patients. PMID- 4025372 TI - Polypharmacy. Causes, consequences, and cure. PMID- 4025371 TI - Pure primary hyperaldosteronism due to adrenal cortical carcinoma. PMID- 4025373 TI - Analysis of granulocyte-macrophage progenitor cells in patients treated with recombinant interferon alpha-2. AB - The most common dose-limiting toxicity of alpha interferon has been leukopenia. It is well documented that interferon inhibits human multipotential, erythroid, and granulocyte-macrophage progenitor cells in vitro. Granulocyte-macrophage progenitor cells were evaluated by a colony-forming assay in patients treated with recombinant interferon alpha-2, and results of the assay were correlated with histologic findings in the same bone marrow aspirates and biopsy specimens from the same patients. Eleven patients received 10 million units/m2 interferon subcutaneously thrice weekly for three months. The bone marrow was evaluated on Day-3 (pretreatment) and Day 10 of treatment. Colony-forming granulocyte macrophage cell count fell from 40.9 +/- 7.6 colonies per 10(5) cells before treatment to 9.3 +/- 1.2 at Day 10 (mean +/- SE, p less than 0.001). It is concluded that the leukopenia induced by interferon is caused by inhibition of maturation of marrow progenitor cells preventing the repopulation of the peripheral blood. PMID- 4025374 TI - Benefit of intravenous IgG replacement in hypogammaglobulinemic patients with chronic sinopulmonary disease. AB - Seven patients with hypogammaglobulinemia and chronic sinopulmonary infections were treated with a preparation of intravenous gammaglobulin. In order to maintain levels of serum IgG at greater than 500 to 750 mg/dl four weeks after infusion, 0.6 g/kg was administered every month. Stable serum levels were achieved after three to eight months. After six to 12 months of this regimen, there was significant reduction in acute infections requiring hospitalization, amelioration of clinical and radiographic evidence of chronic maxillary sinusitis, and improvement in pulmonary symptoms and pulmonary function test results. The administration of increased amounts of IgG intravenously is of benefit in patients with chronic sinopulmonary infections. PMID- 4025375 TI - Cerebrospinal fluid lymphocytosis in acute bacterial meningitis. AB - Cerebrospinal fluid lymphocytosis (more than 50 percent lymphocytes or mononuclear cells) occurred in 14 of 103 cases of bacteriologically proved acute bacterial meningitis. Patients with cerebrospinal fluid lymphocytosis accounted for 32 percent (13 of 41) of all patients with bacterial meningitis with a cerebrospinal fluid white blood cell concentration of 1,000/mm3 or less. Cerebrospinal fluid lymphocytosis was significantly more common in neonates and in those without meningismus, but occurred in all ages and without any clear identifying clinical characteristics. The most common etiologic organisms were Streptococcus pneumonia (five), Neisseria meningitidis (two), and Hemophilus influenzae (two). Cerebrospinal fluid lymphocytosis is common in acute bacterial meningitis when the cerebrospinal fluid white blood cell concentration is below 1,000/mm3. It is therefore of little value in differentiating bacterial meningitis from viral, fungal, and tuberculous meningitis. PMID- 4025376 TI - Shock and death in a 43-year-old woman. PMID- 4025377 TI - Correlation of a quinidine-induced platelet-specific antibody with development of thrombocytopenia. AB - The rapidity by which drug-dependent antiplatelet antibodies can develop is not known, since patients are only studied during or after the episode of thrombocytopenia. This report describes the development of quinidine-induced immune thrombocytopenia in a healthy volunteer during a drug study. The thrombocytopenia developed within two weeks of initiation of quinidine therapy. During the thrombocytopenic episode, but not before receiving the drug, the patient had an IgG antiplatelet antibody that bound to control platelets in the absence of the drug. This antibody was absent when the drug was discontinued and the platelet count rose. The patient's acute serum also induced the release of serotonin from control platelets, and the reaction was enhanced by quinidine. This indicates that drug-dependent antiplatelet antibodies can develop rapidly and supports the hypothesis that quinidine-induced thrombocytopenia is due to a quinidine-dependent platelet-specific IgG. PMID- 4025378 TI - Clostridium septicum septicemia with identical metastatic myonecroses in a granulocytopenic patient. Infectious disease emergency. AB - Clostridium septicum is a gram-positive, sporulating spindle-shaped rod. Gas gangrene secondary to trauma is not uncommon. However, nontraumatic clostridial infection causing myonecrosis is quite unusual. This is a unique case report of Clostridium septicum bacteremia with two simultaneously evolving metastatic foci of myonecrosis of the left arm and right thigh that developed in a patient with lymphoma when he became granulocytopenic during his hospital course. PMID- 4025379 TI - Chronic interstitial pulmonary fibrosis following Mycoplasma pneumoniae pneumonia. AB - An unusual case of chronic interstitial fibrosis that developed as a sequela of Mycoplasma pneumoniae pneumonia is described. Predominant manifestations included progressive exertional dyspnea, shortness of breath, persisting lung infiltrates, low lung volumes, and low pulmonary diffusing capacity. Open lung biopsy one year after the acute stage of mycoplasma pneumonia revealed focal interstitial fibrosis with early pleural thickening, hypertrophic alveolar lining cells, and peribronchiolar lymphoid cell infiltrates. Improvement in clinical manifestations, radiologic findings, and pulmonary function results occurred with steroid therapy. PMID- 4025381 TI - Advances in cephalosporin therapy: beyond the third generation. PMID- 4025380 TI - Reversible hyperthyrotropinemia, hyperthyroxinemia, and hyperprolactinemia due to adrenal insufficiency. AB - This 55-year-old woman presented with primary adrenal insufficiency that led to multiple endocrine gland dysfunctions. Despite symptoms suggestive of hypothyroidism, she had mildly elevated serum thyroid hormone levels associated with elevated thyrotropin levels, hyperprolactinemia, and mild hypercalcemia. These abnormalities corrected with corticosteroid replacement but could be reproduced, in part, when the corticosteroids were temporarily withdrawn. The findings in this patient suggest that physiologic concentrations of glucocorticoids modulate prolactin secretion and the pituitary-thyroid axis. Adrenal insufficiency should be considered in the differential diagnosis of hyperprolactinemia and hyperthyrotropinemia with or without associated hyperthyroxinemia. PMID- 4025382 TI - Pharmacokinetics of the third-generation cephalosporins. AB - The pharmacokinetics of 10 of the newer, third-generation cephalosporins are reviewed. Important features are tabulated. Generalizations are made about structure-activity relationships, relationships between kinetic features, minimal inhibitory concentrations, dosage regimens, and tissue penetration. Tissue levels of ceftazidime are given as examples. These newer chemotherapeutic agents do not possess unique pharmacokinetic properties, but a combination of high antimicrobial activity, safety, and straightforward kinetics facilitates their use in a number of different clinical settings. PMID- 4025383 TI - Treatment of community-acquired pneumonias. AB - Community-acquired pneumonia resulting in hospitalization may have a mortality rate of 10 to 25 percent. The exact incidence of community-acquired pneumonia is unknown because it is not a reportable disease. The etiologic spectrum appears to be changing. Streptococcus pneumoniae causes most of the cases; the rank ordering of other pathogens is uncertain. With the exception of Legionella, colonization of the upper respiratory tract usually precedes clinical pneumonia. Subtle aspiration of the posterior pharyngeal flora accounts for the majority of pneumonias. The need for prompt antibiotic therapy mandates an efficient approach to diagnosis, although it is often difficult to establish a precise etiology. Empiric therapy is often initiated prior to an etiologic diagnosis, and should be as specific as possible. Initial choice of therapy is dictated by the clinical presentation (e.g., "bacterial-like" or "viral-like"), inquiries into the possibility of aspiration or gram-negative pneumonia, and the results of gram stain examination. When the clinical presentation and Gram-stain results are consistent with pneumococcal pneumonia, penicillin is the drug of choice. A more obtuse presentation in an otherwise healthy patient may call for erythromycin to cover Legionella and Mycoplasma. "Marginally compromised" hosts, such as alcoholics, patients with chronic obstructive pulmonary disease, and elderly nursing home patients, may require empiric broad-spectrum cephalosporin therapy for the first few days. Prevention of pneumonia using available vaccines must be emphasized. PMID- 4025384 TI - Comparative toxicities of third-generation cephalosporins. AB - Data on the adverse effects experienced by 2,539 patients who received ceftazidime were compared with adverse effects reported with cefoperazone, cefotaxime, ceftizoxime, and moxalactam. There were 216 such reactions among the ceftazidime-treated patients; 158 patients (6.2 percent) had reactions that were possibly or probably drug-related. The clinical and laboratory safety profile of ceftazidime in regard to renal, hepatic, hematopoietic, and hemostatic parameters compared favorably with that of other third-generation cephalosporins. An increased serum creatinine level was observed in 0.8 percent of ceftazidime treated patients, an increased blood urea nitrogen level in 1.6 percent, hepatic abnormalities in approximately 6 percent, diarrhea in 1.3 percent, pseudomembranous colitis in 0.12 percent, increased prothrombin time in 0.5 percent, and clinical bleeding in none. The incidence of colonization (3.8 percent) and superinfections (3 percent) associated with ceftazidime therapy was comparable to rates with other agents in this class. PMID- 4025385 TI - Noonan syndrome: the changing phenotype. AB - Among the multiple congenital anomalies (MCA) syndromes, the Noonan syndrome (NS) is a cardiofacial syndrome in which affected individuals may be short and mildly mentally retarded. Autosomal dominant inheritance of Noonan syndrome with variable expressivity has been documented in many families. Genetic heterogeneity has been postulated in Noonan syndrome because of the wide phenotypic variability, the relatively high incidence, and the occasional recurrence in sibs with apparently normal parents. Clinical variability is usual in autosomal dominant disorders, and mildly affected individuals may be difficult to recognize as gene carriers. Thus, a family with two or more affected children may simulate autosomal recessive inheritance. We have studied serial and family photographs of NS individuals in order to assess the likelihood of gene carriers' being missed in genetic studies. We have confirmed wide clinical variability within families, and more importantly, we have documented marked change of phenotype with age from the newborn period, infancy, childhood, and adolescence to adulthood. Manifestations in adults may be subtle and some without a known heart defect or other medically significant problems may have been considered normal in the past. Our study, while not ruling out causal heterogeneity, suggests that the change of phenotype with age may have been falsely perceived as clinical heterogeneity. A particular and subtle phenotype must be searched for in parents of affected children. PMID- 4025386 TI - Gaucher disease: comparative study of acid phosphatase and glucocerebrosidase in normal and type-1 Gaucher tissues. AB - Acid phosphatase activity was determined in serum, cultured fibroblasts, and peripheral blood lymphocytes of six splenectomized adult patients with non neuropathic Gaucher disease in two Canadian families. Elevated levels of serum acid phosphatase activity (520-711% of normal) were found in four patients who also developed orthopedic complications associated with Gaucher disease, including intermittent bone pain, arthritis, collapse of femoral head, and pathological fractures. Serum acid phosphatase activity in two patients who do not have bone involvement were found to be within the normal range. Contrary to the serum enzyme, acid phosphatase activity in lymphocytes and cultured fibroblasts of all of the patients was within the normal range. Deficient glucocerebrosidase (7.5-15.5% of normal) and acid beta-glucosidase (13.8-27.8% of normal) activities were noted in all probands. Similarly, normal levels of fibroblast and lymphocyte acid phosphatase activity were found in Gaucher heterozygotes whose glucocerebrosidase activity was about 50% of normal. Acid polyacrylamide gel electrophoresis and acid phosphatase activity staining of the patients' sera showed that the elevated acid phosphatase is isozyme type 5 osteoclastic origin. The apparent Michaelis constant, Km, of fibroblast glucocerebrosidase for the natural substrate was 0.6 +/- 0.1 mM for controls and 0.6 +/- 0.2 mM for the patients. These data suggest that the assay of serum acid phosphatase activity for the presumptive diagnosis of Gaucher disease is not completely reliable and that the elevated level of serum acid phosphatase in Gaucher disease is most likely a secondary phenomenon which may be indicative of bone involvement in some patients with this disorder. It also demonstrates the clinical heterogeneity of type 1 Gaucher disease, even among full sibs of the same heterozygous parents. PMID- 4025387 TI - Differential diagnosis in young women with oligomenorrhea and the pseudo pseudohypoparathyroidism variant of Albright's hereditary osteodystrophy. AB - Oligomenorrhea was the reason for consultation in three individuals (two sisters and one unrelated woman) with the pseudo-pseudohypoparathyroidism (PPHP) variant of Albright's hereditary osteodystrophy (AHO). All had short stature, Ullrich Turner-like signs, acral anomalies typical of AHO/brachydactyly E, and hypogonadism. One of the three individuals also had reduced erythrocyte NS (a membrane nucleotide regulatory protein that is required for functional coupling of stimulatory hormone receptors and catalytic adenylate cyclase) activity as described in the pseudohypoparathyroidism variant of AHO. The differential diagnosis of young women with the PPHP phenotype is discussed with special reference to Ullrich-Turner syndrome, brachydactyly E, the "resistant ovary" syndrome, and acrodysostosis. PMID- 4025388 TI - Osteodysplastic primordial dwarfism: report of a further patient with manifestations similar to those seen in patients with types I and III. AB - We describe a female infant with low birthweight osteodysplastic microcephalic dwarfism. The child has many manifestations in common with those seen in osteodysplastic primordial dwarfism types I and III. The classification of this heterogeneous group of disorders is discussed in the light of the above case. PMID- 4025389 TI - Similarity of effects--experimental hyperthermia as a teratogen and maternal febrile illness associated with oromandibular and limb defects. AB - Experimental hyperthermia in pregnancy causes oromandibular and limb anomalies. In humans, hyperthermia has been suspected of being teratogenic. Two patients were investigated; both had limb defects and one had oromandibular anomalies. Their mothers had a febrile illness at about the 10th wk of gestation. The similarity of defects produced by experimental hyperthermia and those reported here is striking. PMID- 4025390 TI - Chondrodysplasia punctata in an infant with duplication 16p due to a 7;16 translocation. AB - This paper describes a newborn with a number of clinical manifestations compatible with duplication 16p due to a 46, XY, -7, +der (7), t(7;16) (p22;p13) pat karyotype. In addition, the baby had chondrodysplasia punctata, whose distribution of lesions did not match any of the well-documented forms of these disorders. The baby also had microcornea and lacked a gallbladder, two features, in addition to chondrodysplasia punctata, that have not previously been noted in cases of duplication 16p. PMID- 4025391 TI - Phenotype-karyotype correlations in dup(18q): report of a case and review. AB - We report on a case of dup(18q) due to de novo translocation 46,XX, 21,t(18;21)(18qter----cen----21qter). The patient had many characteristic signs of full trisomy 18 except for internal organ malformations and early death. We review the phenotype-karyotype correlations between full trisomy 18 and dup(18q) and discuss the possibility of the existence of "critical zone(s)" at the proximal or/and distal region of 18q responsible for most signs of trisomy 18, such as congenital heart defect and early death. PMID- 4025392 TI - Plasma/serum myoglobin in prenatal diagnosis of Duchenne muscular dystrophy. PMID- 4025393 TI - The role of mesenchyme-like tissue in the pathogenesis of thanatophoric dysplasia. AB - We have studied the light microscopic, transmission, and scanning electron microscopic (SEM) findings in 13 cases of thanathophoric dysplasia (TD) and 4 control infants. In the TD growth plate, areas with less abnormal cartilage and bone alternated with areas of severely abnormal cartilage and bone. These latter abnormal areas were always found around tongues of apparent mesenchymal tissue that appeared to penetrate from the investing perichondrium and periosteum. The ultrastructure of the less abnormal areas was similar to that of the control infants, including cell and matrix structure as well as mineralization. The abnormal cartilage and bone had many ultrastructural abnormalities that were also found in the adjacent mesenchymal tissue. The mesenchymal cells, adjacent chondrocytes, and osteoblasts contained dilated endoplasmic reticulum and moderately large intracytoplasmic vacuoles. In the area adjacent to the cartilage, the matrix of the apparent mesenchyme contained thin collagen fibers and proteoglycan granules, whereas the matrix adjacent to the bone contained thick bundles of short collagen fibers. The matrix of the surrounding cartilage and bone resembled the adjacent matrix in the mesenchyme. In addition, many vesicular structures or osmiophilic particles were found in the matrix of the mesenchyme and adjacent cartilage and bone. SEM examination showed normal and abnormal bone trabeculae adjacent to each other. In the abnormal trabeculae, there were large, densely packed osteoblastic and osteocytic lacunae. The calcified collagen fibers had a random orientation, in contrast to the longitudinal orientation in the relatively normal bone. Chemical studies of collagen in the metaphyses of bones from five infants with TD showed a small amount of collagen type III (less than 5%), which was not found in three control infants. Thus, a basic pathogenetic mechanism in the skeletal abnormalities of TD appears to be the focal replacement of the growth plate and periosteum by persisting abnormal mesenchymal-like tissue from which the abnormal bone originates. PMID- 4025394 TI - Unusual type of brachydactyly associated with short stature and facial anomalies. A new syndrome? AB - We report on a 10-year-old boy with short stature, mild microcephaly, malar hypoplasia, highly arched palate, prominent upper incisors, micrognathia, and unusual digital anomalies involving the proximal phalanges of fingers 2-5 of both hands. To our knowledge, this is a hitherto undescribed syndrome. PMID- 4025395 TI - A new family with fra(10)(q25): spontaneous expression and 100% expression with 100 microM BrdU. AB - We report on a family with fra(10)(q25) ascertained through a female with multiple minor anomalies and present in her phenotypically normal father and other family members. The site is expressed spontaneously at levels of 9% in lymphocytes, 2% in lymphoblasts, and 6% in skin fibroblasts. Expression frequency is significantly enhanced to levels as high as 100% by addition of BrdU to the culture medium. The consistently high level of induced expression in lymphoblasts from the proband facilitates analysis of the biochemical and structural bases of fragile site expression. PMID- 4025396 TI - An X-linked recessive basal ganglia disorder with mental retardation. AB - We report a previously apparently undescribed, X-linked recessive basal ganglia disorder segregating in three generations of one family. The affected patients were variably mentally retarded, although some showed strengths in oral reading and memory. Most affected males had frontal bossing and increased head circumference with large calvaria in relation to facial bones. Their height and weight did not differ from that of other relatives; testicular size was average, chromosomes were normal, and results of laboratory investigations for known metabolic disorders were normal. All patients examined had neurological impairment, including persistent frontal lobe reflexes, cogwheel rigidity, postural changes, and Parkinsonian-type tremors. Some had strabismus; several had seizures. Although carriers of the condition were not consistently abnormal, two had suggestive signs. No definitive indication of the disorder was documented in infancy in any affected male, and it is possible that this could be due to lack of careful prospective clinical evaluation rather than to the absence of symptoms in early life. PMID- 4025397 TI - A new X-linked mental retardation syndrome. AB - We have studied a three-generation family with 11 moderately to severely retarded males and three mildly retarded females (presumably manifesting carriers). The patients have a phenotype different from that of all other previously described types of X-linked MR (XLMR). These include short stature, macrocephaly, "coarse" facial appearance including prominent forehead and supraorbital ridges, hypertelorism, broad nasal tip with anteverted nostrils, and thick lips. All postpubertal males had macroorchidism (volume greater than 25 ml). Chromosomes were normal including fragile X analysis. X-ray findings of skull, spine, and hands were normal. The intellectually normal relatives do not resemble their affected relatives except for increased head size and testicular size. These findings suggest a new variant of XLMR different from fragile X-linked MR, the Coffin-Lowry syndrome, and other XLMR conditions. PMID- 4025398 TI - Weaver syndrome with pes cavus. AB - Few cases have been described of the Weaver syndrome, an overgrowth syndrome with advanced skeletal age. Here we report bilateral pes cavus in an affected girl. PMID- 4025399 TI - Variance components analysis of forced expiration in families. AB - Familial aggregation of forced expiration (as measured by forced expiratory volume in 1 sec (FEV1) and the ratio of this to total forced vital capacity (FEV1/FVC) was analyzed in 439 adult members of 108 families ascertained through control patients who had participated in a genetic and epidemiologic study of chronic obstructive pulmonary disease. Residual values for both FEV1 and FEV1/FVC obtained from regression on age, sex, race, and cigarette smoking (and height for FEV1) were used in a variance components analysis to assess the relative importance of genetic and nongenetic factors influencing familial aggregation of pulmonary function among adults. For both residual FEV1 and residual FEV1/FVC, the "best" model among a series of genetic and nongenetic models was a simple additive genetic model. A modified score test, which is robust to the assumption of multivariate normality, was used to test the significance of these estimated components. Under the most parsimonious model, additive genetic variation accounted for 28% of the variation in residual FEV1 in 108 families and 24% of the variation in residual FEV1/FVC. After outlying individuals were identified by examining goodness-of-fit statistics, the simple genetic model still gave the best fit to these data. There was little indication of non-normality in FEV1 in these families; however, FEV1/FVC did show evidence of non-normality when examining goodness-of-fit statistics. This genetic component contributing to the distribution of forced expiration may be a factor in the familial aggregation of certain respiratory diseases. PMID- 4025400 TI - Vascular abnormalities in a fetus with multiple pterygia. AB - We describe a 16-week fetus with a lethal multiple pterygium syndrome and hydrops. No bony abnormalities were noted on radiographic or anatomical examination. A prominent meshwork of dilated, thin-walled vessels was present in the subcutis over the entire body. This abnormal vascularity may have caused pterygium formation and death of the fetus. PMID- 4025401 TI - Anomalies in an infant with Nager acrofacial dysostosis. AB - We report on an infant with Nager acrofacial dysostosis, laryngeal and epiglottic hypoplasia, abnormal septation of the right middle lobe of the lung, hypoplastic right first rib, and dislocation of the right hip. These findings suggest the possibility that patients with the Nager syndrome may have other developmental defects in addition to the facial and acral anomalies associated with this syndrome. PMID- 4025402 TI - Krabbe disease: increased incidence in a highly inbred community. AB - Krabbe disease (globoid cell leukodystrophy) was found with very high incidence (6/1,000 live births) in a large Druze kindred in Israel. The clinical data on 12 of the affected children demonstrated clinical variability even though these children are homozygous for the same mutation by descent from a common ancestor. PMID- 4025403 TI - Reduction of fragile X expression in blood after cryopreservation. AB - Frequency of fragile X expression was investigated before and after cryopreservation (-196 degrees C) in the blood of 4 affected males, 3 fragile X carriers and in a fibroblast cell strain from a fragile X male fetus. The results indicate that there is a significant decrease (p less than 0.05) in the frequency of the fragile X expression in lymphocytes after cryopreservation, as compared to the fresh blood, but not in fibroblasts. This suggests that cryopreserved blood specimens may not be suitable for fragile X analysis. PMID- 4025404 TI - Apert syndrome with frontonasal encephalocele. AB - We describe a female infant with Apert syndrome (acrocephalosyndactyly, type I) and a frontonasal encephalocele with unremarkable family history. PMID- 4025405 TI - Ruvalcaba syndrome. PMID- 4025406 TI - Relationship of upbringing to later behavior disturbance of mildly mentally retarded young people. AB - Factors were examined that might explain the higher rate of behavior disturbance found in a population of mildly mentally retarded young adults compared with nonretarded peers. Results showed that neurological impairment, found in one third of the retarded subjects, was not a factor. Three results supported the explanation that instability of upbringing was responsible for the difference in behavior disturbance: a significant relationship was found between upbringing and behavior disturbance for both retarded and nonretarded subjects; conditions of upbringing were significantly more unstable among the retarded than nonretarded subjects; and when upbringing was held constant for both sets of subjects, no differences were found in behavior disturbance. PMID- 4025407 TI - Self-preservation ability and residential fire emergencies: replication and criterion-validity study. AB - In a previous study MacEachron and Janicki (1983) used the National Bureau of Standards approach to measuring self-preservation ability to estimate the prevalence of such skills in the New York State service population of 47,000 developmentally disabled persons. In the present study we replicated their results in another state serving 8,000 developmentally disabled persons. Moreover, we found that the operationalized National Bureau of Standards' measurement was a good predictor of a criterion measure of self-preservation ability. These results suggest the general feasibility of using these measurements to estimate prevalence, focus intervention strategies and capital expenditures to specific areas of need, and provide information to facilitate appropriate residential placement. PMID- 4025408 TI - Everyday cognition among mildly mentally retarded adults: an ethnographic approach. AB - Participant-observation techniques were used to study the everyday cognition and problem-solving process in marketing tasks defined and organized by mildly mentally retarded adults. Observations were systematized in terms of five primary functional units: logistics, activity goal, item selection, quantity selection, and payment strategy. Results revealed five "composites" of strategic behavior used by these adults that represent characteristic ways of addressing problematic aspects of this everyday task environment. An association between composite and early life experiences was also shown. These results were used to characterize further the nature of everyday cognitive behavior, including discussions of the nature of everyday performance, the "externalization" of cognition through the explicit design of settings, and the presence and utility of retarded adult's metacognitive skills. PMID- 4025409 TI - Situational anxiety and everyday life experiences of mildly mentally retarded adults. AB - Situational (A-state) anxiety reactions of mildly mentally retarded adults were studied using a self-report anxiety inventory under four sets of conditions ranging from presumed high to low stress. The effects of work experiences and social activity on situational anxiety were also examined, as was the relationship between anxiety and performance on an observational task. Significant results show higher overall anxiety under stressful conditions and lower anxiety scores for individuals who are employed and who are socially active. A high positive correlation was found between anxiety level and performance. The implications of these findings for understanding the emotional life and everyday competence of retarded adults were discussed. PMID- 4025410 TI - Variables related to body-weight status of mentally retarded adults. AB - Mentally retarded male and female adult subjects displayed mean body weights in excess of their ideal weights; excessive body weight of females was also apparent in comparison to normative data for the United States. Maintenance of appropriate weight appeared to be more likely in a controlled residential setting than in the natural home environment. These sex and environmental relationships could not be explained by medication and dietary programming differences, and age, race, and level of retardation were unrelated to body weight. PMID- 4025411 TI - Controlling pica by components of an overcorrection procedure. AB - Previous studies have shown that pica, the ingestion of inedible objects, can be effectively controlled in mentally retarded subjects using a two- or three component overcorrection procedure or with one of these components in conjunction with another response-reduction procedure, differential reinforcement of other behavior. The present study showed that one of the components, oral hygiene, could eliminate pica by 2 retarded subjects when used alone. Although oral hygiene was the most effective component, each of the other components, tidying and personal hygiene, did decrease pica. In a later phase we found that a number of different therapists could easily and effectively implement the oral hygiene procedure. PMID- 4025412 TI - Influence of planning time and first-move strategy on Tower of Hanoi problem solving performance of mentally retarded young adults and nonretarded children. AB - Because the ability to plan ahead is essential for successful solution of transformation problems, it is reasonable to assume that planning time will be positively related to performance. In two experiments using a computer-interfaced Tower of Hanoi problem, however, the planning time of retarded young adults was, on the average, as long as or longer than the planning time of higher performing nonretarded children. In neither group was there a reliable correlation between planning time and performance. There were group differences in preferred strategies, which we speculated were associated with a deeper search capacity available to the nonretarded children. What takes place during planning time is a more relevant source of group and individual differences than is the duration of planning time. PMID- 4025413 TI - Spontaneous rehearsal by mildly mentally retarded children and adolescents. AB - The use of a rehearsal strategy by 10-, 12-, and 14-year-old mildly mentally retarded children and adolescents was investigated using a self-paced recall readiness task. This task, in contrast to those typically used to study rehearsal by retarded individuals, allowed subjects to study items in any order as many times as desired. Each age group used rehearsal, as indicated by increasing study time patterns and the number of repetitions per item. We suggest that previous studies have failed to detect rehearsal by retarded persons because the tasks used have constrained the range of possible types of study behavior. The implication of this finding for rehearsal deficit theories was discussed. PMID- 4025414 TI - Comparison of word-supply and word-analysis error-correction procedures on oral reading by mentally retarded children. AB - An alternating treatments design was used to measure the differential effects of two error-correction procedures (word supply and word analysis) and a no-training control condition on the number of oral-reading errors made by four moderately mentally retarded children. Results showed that when compared to the no-training control condition, both error-correction procedures greatly reduced the number of oral-reading errors of all subjects. The word-analysis method, however, was significantly more effective than was word supply. In terms of collateral behavior, the number of self-corrections of errors increased under both intervention conditions when compared to the baseline and no-training control conditions. For 2 subjects there was no difference in the rate of self corrections under word analysis and word supply but for the other 2, a greater rate was achieved under word analysis. PMID- 4025415 TI - Differences in semantic processing speed of mentally retarded and nonretarded persons. AB - A modified Sternberg choice-reaction time procedure was used to compare differences in the speed with which mentally retarded and nonretarded adults were able to retrieve recently stored information from short-term memory and process permanently stored semantic information. Results revealed that the retarded adults were slower than were the nonretarded adults in both domains of processing; the relative magnitude of "processing inefficiency" exhibited by the retarded subjects was quite similar across the two domains (47% and 57% as efficient as the nonretarded subjects in short-term and long-term memory processing, respectively). This similarity suggests that inefficient processing may represent a fundamental deficiency of retarded individuals resulting from the inefficient execution of some central processing mechanism. PMID- 4025416 TI - High-speed memory-scanning task performance of mildly mentally retarded and nonretarded individuals. AB - Mildly mentally retarded and CA-matched nonretarded subjects were required to memorize lists of English letters and Chinese characters varying in length from one to four elements. Single probe letters or characters were presented following memorization. The subject responded yes if the probe was a member of the memorized list or no if it was not. Subjects were encouraged to respond quickly but without making errors. Choice reaction times (RTs) were measured from probe onset to the depression of the yes or no response key upon which the index finger of the appropriate hand rested. Retarded subjects demonstrated slower overall choice mean RTs relative to the nonretarded group. Results also suggest that the processing difference lies in the memory scanning as opposed to the encoding/decision/response component of the linear model (Sternberg, 1969); however, this suggestion is limited by the disparity of the group data sets. PMID- 4025417 TI - Effects of different living settings on the performance of mentally retarded individuals. AB - Motivation for adult attention and support, wariness, and expectancy of success over a 2-year period were assessed for 58 mentally retarded individuals residing in either large central institutions, regional centers, or group homes. Males were found to be more responsive to social reinforcement than were females in all living settings. Wariness was found to increase over time in the large central institutions, whereas it decreased in the smaller settings. Individuals with greater preinstitutional social deprivation had a lower expectancy of success. In addition, over the 2-year period, the expectancy of success of individuals from high-deprived backgrounds remained low, whereas it increased for individuals from less socially deprived preinstitutional backgrounds. PMID- 4025418 TI - Stigma perception: social comparison among mentally retarded persons. AB - Two studies were conducted in order to determine whether a group concept problem (i.e., relatively unfavorable opinions of other retarded persons; Gibbons, 1981): (a) includes retarded persons' perceptions of their peers' social desirability, such as dating appeal and physical attractiveness; (b) occurs among persons living in community settings; and (c) differs by sex. Results provided affirmative answers for all questions and indicated that the problem is most severe among community women. In addition, there was evidence of self-derogation among both community-based and institutionalized retarded persons in terms of social success (e.g., dating behavior). I suggested that this type of person perception may be interfering with retarded persons' social behavior and their adjustment to community-based and institutional environments. PMID- 4025419 TI - Diagnostic tests in obstetrics: a method for improved evaluation. AB - With the proliferation of diagnostic tests in obstetrics, several recurrent questions arise. How does one determine whether one diagnostic test is superior to another available test? What test cutoff value best separates diseased from nondiseased patients? How much does performance of additional tests assist in arriving at a correct diagnosis? This article reviews a simple yet sophisticated analytic technique, the receiver operating characteristic curve, and demonstrates its application to several obstetric diagnostic tests. Receiver operating characteristic curve analysis is used to select a cutoff value for the 1-hour glucose tolerance test, to compare amniotic fluid tests of fetal lung maturity, and to determine the optimal combinations of factors and overall performance of the fetal biophysical profile. The value of receiver operating characteristic curve analysis lies in providing a clear graphic analysis of the performance of diagnostic tests over their entire range of values. It also provides the starting point for evaluating the costs and benefits of alternative cutoff points in differing clinical settings. PMID- 4025420 TI - Cesarean section deliveries among adolescent mothers enrolled in a comprehensive prenatal care program. AB - A comparison was made of the incidences of cesarean section deliveries between mothers 18 years of age or younger and those 19 to 21 years of age, all of whom were enrolled in a comprehensive program of prenatal care. Also compared were the indications for surgical delivery between the two groups. The rate of cesarean section deliveries was 8.7% among mothers 18 years of age or younger, compared to 14.5% among mothers 19 to 21 years of age. The general-ward cesarean section rate at the same hospital was 19.4%. Since maternal height and weight, and infant's birth weight may affect the diagnosis of cephalopelvic disproportion, these parameters were also evaluated. However, these did not differ significantly between mothers 18 years of age or younger and those 19 to 21 years of age or between vaginal and surgical births in mothers 18 years of age or younger. Thus, cephalopelvic disproportion did not contribute importantly to the cesarean section rate. PMID- 4025421 TI - Association of elective repeat cesarean delivery and persistent pulmonary hypertension of the newborn. AB - Seventy-one cases of persistent pulmonary hypertension of the newborn have been reviewed in an attempt to identify possibly preventable causes. Three groups of infants were identified. The first group consisted of 36 infants with evidence of perinatal asphyxia. The second group was made up of 23 infants who exhibited a variety of associated factors including pneumonia, septic shock, and congenital diaphragmatic hernia. A third group included 12 infants delivered by elective repeat cesarean section. Infants in the third group did not have evidence of perinatal asphyxia, meconium aspiration, or infection. Chest roentgenograms revealed amniotic fluid aspiration in seven cases, retained lung fluid in three cases, and normal findings in two cases. All 12 infants in the third group developed respiratory distress which eventually progressed to respiratory failure and persistent pulmonary hypertension of the newborn. These data suggest that infants of elective repeat cesarean deliveries are at risk for developing persistent pulmonary hypertension of the newborn and constitute a group of patients with a potentially preventable course of events. PMID- 4025422 TI - Thiazide diuretics and bone mineral content in postmenopausal women. AB - This retrospective study of 54 postmenopausal women taking thiazide diuretics found that bone mineral measurements and bone fracture prevalence did not differ significantly from those of matched control subjects. Matching on the variables of type of menopause (surgical/nonsurgical), years postmenopausal, duration of estrogen therapy (if any), daily intake of dietary and supplemental calcium and vitamin D, and Quetelet index was done without knowledge of the bone mineral measurements. Bone mass was recorded as the bone mineral content and bone density of the distal and midshaft radius. Only fractures associated with osteoporosis (hip, rib, vertebrae, and wrist) were recorded. This study suggests that thiazide diuretics do not provide protection against osteoporosis. PMID- 4025423 TI - Asymptomatic parturient women with high-virulence bacteria in the amniotic fluid. AB - This study describes the postpartum course of asymptomatic parturient women who had greater than or equal to 10(2) cfu of high-virulence (HV) bacteria per milliliter of amniotic fluid. Of 60 asymptomatic parturient women with greater than or equal to 10(2) cfu of HV bacteria per milliliter of amniotic fluid, 27 (48%) remained asymptomatic in the puerperium, 16 (27%) developed fever only, and 17 (28%) developed endometritis. In asymptomatic versus symptomatic women, there were no statistically significant differences in number or type of isolates or in length of membrane rupture or labor-to-collection interval. However, there were significant differences in the intervals from collection to delivery and in the rate of cesarean section delivery. For comparison, 40 of these patients were matched with women in whom only low-virulence organisms were detected in the amniotic fluid. In the HV group, 16 women (40%) remained asymptomatic, 15 (37.5%) developed fever only, and nine (22.5%) had endometritis. In the low-virulence group, 27 women (67.5%) remained asymptomatic, 10 (25%) developed fever only, one (2.5%) developed endometritis 10 days post partum, and two (5%) had other infections (p less than 0.01). Clinically evident uterine infection depends upon type and numbers of bacteria in utero, duration of bacteria in utero, and route of delivery. PMID- 4025424 TI - Maternal heart rate in pregnancy. AB - Serial morning heart rates were obtained from 10 women runners prior to and during pregnancy. By 8 weeks' menstrual age, maternal heart rate had risen 8 bpm with an overall pregnancy-associated increase of 16 bpm. Potential mechanisms are discussed. PMID- 4025425 TI - Vitamin E concentrations in serum of newborn infants after topical use of vitamin E by nursing mothers. PMID- 4025426 TI - Laser treatment of cervical intraepithelial neoplasia in an office setting. AB - One hundred eighty-six patients underwent carbon dioxide laser treatment of cervical intraepithelial neoplasia. Both vaporization and excisional procedures were performed in an office setting without difficulty. Thirty-nine patients (36.4%) had grade 1, 38 (35.6%) had grade 2, and 30 (28%) had grade 3. Among 107 patients followed up for at least 6 months, there were two treatment failures (5.1%) in the grade 1 group and no treatment failures for grades 2 and 3. The overall success rate for all grades of cervical intraepithelial neoplasia was 98% for a single laser treatment. Our ability to use the laser to excise a specimen, as well as to treat large and endocervical lesions, allowed the office treatment of many patients who would otherwise have required hospitalization. PMID- 4025427 TI - Conservative management of small bowel obstruction. AB - Intestinal Cantor tubes were used in the management of 69 gynecologic patients with pelvic malignancies who presented with small bowel obstruction. Small bowel obstruction was secondary to radiation injury, persistent or recurrent carcinoma, or postoperative adhesions. Thirty-one patients (45%) in this series had successful resolution of their small bowel obstruction with a Cantor tube, including 12 of 14 patients (86%) with postoperative adhesions. Complete obstruction of the small bowel was the only prognostic factor definitely associated with tube failure. Seventy percent of all patients had successful passage of the tube on one attempt, and no major complications were encountered. The Cantor tube has proved to be safe, effective, and easy to use, and guidelines for the management of it are included. Cantor tube decompression should be considered in the initial management of small bowel obstruction, since a significant percentage of the patients with this condition will not require surgical intervention. PMID- 4025428 TI - Fetal heart rate accelerations and fetal movements in twin pregnancies. AB - The rate of fetal heart rate accelerations associated with fetal movements to total fetal movements of twin pregnancies was found to be significantly lower than that of pregnancies with singleton infants. The number of fetal heart rate accelerations was similar. As fetal heart rate accelerations are reflective of fetal movements, the results indicate increased fetal activity in twins that is related to an additive effect of two normally active fetuses. PMID- 4025429 TI - Experimental evidence for the progress of labor with the increase in the force of cervical dilatation after rupture of the membranes. AB - To examine the mechanical forces involved in cervical distention, actual tensions of the fetal membranes up to the bursting level were measured experimentally with the use of five circular membrane holders that simulate various cervical dilatations (radii 1 to 5 cm). The results show that the force of cervical dilatation with the head alone increases remarkably as the cervix dilates, and this force is always larger than that when the membranes are intact. Thus the membranes appear to interfere with effective cervical dilatation and progress of labor after fixation of the fetal head to the cervix. PMID- 4025430 TI - Uterine and whole body oxygen extractions in the pregnant rabbit under chronic steady-state conditions. AB - Seventeen pregnant rabbits were studied under conscious, unstressed conditions after catheterization of the right ventricle (RV), a femoral artery (A), and a uterine vein (UV). Respiratory gas tensions, pH, and oxygen saturations and contents were determined serially throughout the latter half of gestation. The uterine coefficient of oxygen extraction increased with gestational age (R = 0.86) and became 60.6% +/- 0.3% during the last 4 days of pregnancy. To compare uterine perfusion with whole body perfusion in relationship to oxygen demands, the (Ao2 - UVo2/Ao2 - RVo2) ratio was computed. The ratio was greater than or equal to 1 after 20 days of gestation, which demonstrated that in regard to oxygen demands the rabbit uterus is relatively underperfused compared to the rest of the maternal organism in the last part of pregnancy. A comparison with analogous data in other species demonstrates that the pregnant rabbit, like the guinea pig, has a much lower rate of uterine blood flow than does the pregnant sheep. These interspecies differences in the perfusion rate and oxygen extraction of the pregnant uterus are related to differences in placental structure. PMID- 4025431 TI - Erythrocyte filterability and fetal development in normal pregnancy. AB - The relationship between maternal erythrocyte filterability determined in late pregnancy and infant birth weight was studied in uncomplicated pregnancy. There was a significant positive correlation (r = 0.7671, p less than 0.005). Maternal erythrocyte filterability is suggested to be an indicator of flow state of the placental microcirculation, which affects fetal development. PMID- 4025432 TI - Total sulfhydryl compounds in human seminal plasma. PMID- 4025433 TI - Dickinson's sign: focal uterine softening in early pregnancy and its correlation with the placental site. AB - Focal uterine softening, characteristic of early pregnancy, is usually known as Piskacek's or von Braun-Fernwald's sign but should be attributed to Robert Latou Dickinson, who first described it in 1982. The presence or absence of Dickinson's sign was carefully noted in 1040 pregnant patients seeking abortions. The weeks of gestation, location of uterine softening, and correlation with placental site were also studied. This sign reliably showed the placental site, hence its unequivocal presence nearly proves the presence of intrauterine pregnancy and precludes the existence of tubal pregnancy. It was present in most pregnancies between 6 and 11 menstrual weeks, and its presence after 14 weeks should make menstrual dates suspect or signal the possibility of a septate or bicornuate uterus. PMID- 4025434 TI - The mortality risk associated with hysterectomy. AB - To study the risks of mortality associated with hysterectomy that are specific to age, race, surgical approach, and associated conditions, we used data collected by the Commission on Professional and Hospital Activities during 1979 and 1980. Four hundred seventy-seven deaths were recorded among 317,389 women having abdominal hysterectomies and 46 deaths among 119,972 women having vaginal hysterectomies. The mortality rates for hysterectomy, standardized for age and race, were higher for procedures associated with pregnancy or cancer than for procedures not associated with these conditions (29.2, 37.8, and 6.0 per 10,000 procedures, respectively). Hysterectomies associated with pregnancy or cancer constituted 8% of all hysterectomies performed. However, 61% of all deaths occurred in women with pregnancy- or cancer-related conditions. The mortality rate associated with hysterectomy increased with age and was twice as high among black women. PMID- 4025435 TI - Cord blood glycosylated (glycated) hemoglobin: correlation with maternal glycosylated (glycated) hemoglobin and birth weight. AB - Maternal and cord blood glycosylated hemoglobin levels were measured by an affinity chromatographic method in three groups: normal women (nondiabetic women who gave birth to infants that were normal for gestational age); test women (women who had no evidence of glucose intolerance with screening procedures and who gave birth to large-for-gestational age infants); and women with gestational diabetes. In all cases the level of cord blood glycosylated hemoglobin was approximately 40% less than the corresponding maternal blood levels, and no correlation could be detected between maternal and cord blood concentrations. The reference range for glycosylated hemoglobin in the normal maternal population was similar to that for nonpregnant adults. There was no significant difference in cord and maternal glycosylated hemoglobin levels among the three groups, although a slight upward trend was detected in the diabetic group. There was a lack of correlation of cord and maternal glycosylated hemoglobin with birth weight in all three groups. The implications of these findings are discussed in respect to the usefulness of cord and maternal glycosylated hemoglobin in retrospective screening for gestational diabetes. PMID- 4025436 TI - Intraligamentary pregnancy resulting in a live infant. AB - Presented is the case of a woman with an ectopic pregnancy in the left broad ligament, which resulted in a live, healthy infant. Despite the characteristic history of an abdominal crisis early in pregnancy and complaints of abdominal pain throughout pregnancy, the correct diagnosis was not established until cesarean section. PMID- 4025437 TI - Mondor's disease in the breast. AB - Mondor's disease is thrombophlebitis of a vein on the anterolateral thoracoabdominal wall. When it involves the breast it may cause undue apprehension. The characteristic appearance is described and illustrated. A mammogram is shown. PMID- 4025438 TI - Benign nevus (ephelis) of the uterine cervix. PMID- 4025439 TI - Use of the Deaver retractor for exteriorization of ovarian cysts at laparotomy. AB - A method for the delivery of large benign ovarian cysts through the abdominal incision with use of the Deaver retractor is described. This method has facilitated the intact delivery of 11 large benign ovarian cysts in cases in which the abdominal incision was relatively small without the need of extending or modifying it. PMID- 4025440 TI - Small bowel obstruction secondary to a prior Moschcowitz procedure. AB - The Moschcowitz procedure has been advocated for the correction of large enteroceles. Documented complications of this technique are rare. Following is a review of this procedure with the presentation of a unique delayed complication. PMID- 4025441 TI - Assessing risks of midtrimester amniocentesis. PMID- 4025442 TI - Gestational diabetes and birth trauma. PMID- 4025443 TI - Classification and pathogenesis of vulvovaginal candidiasis. AB - Although candidiasis of the female genital tract is one of the most common of the vaginitides, it is a poorly understood disease entity. Vulvovaginal candidiasis is a monoetiologic disease, but the pathways by which pathogenic expression is attained are sufficiently divergent to constitute a classification schema that influences therapy. For selection of appropriate therapy, the following three broad categories are proposed: (1) primary candidiasis, (2) antibiotic-induced candidiasis, and (3) systemically induced candidiasis. PMID- 4025444 TI - Pharmacokinetic fundamentals of vaginal treatment with clotrimazole. AB - Pharmacokinetic studies with clotrimazole in rats and in humans, following oral and intravenous administration, have shown that clotrimazole is rapidly metabolized. After vaginal treatment with clotrimazole, the small fraction absorbed into the systemic circulation--between 3% and 10% of the dose--is subjected to metabolism and excretion as after oral or intravenous administration. The vaginal availability of clotrimazole is largely dependent on the formulation applied. In contrast, up to 3 days after single application of a vaginal tablet containing 500 mg clotrimazole together with lactic acid, fungicidal amounts of clotrimazole were measured in vaginal fluid, i.e., the single dose serves as a depot in the vagina for at least 3 days. Thus the single dose treatment of vaginal mycosis with clotrimazole offers the advantage of combining a high availability in the vagina with a low availability of systemic circulation and is a means of solving the problem of the patient's noncompliance. PMID- 4025445 TI - The problem of patient compliance. AB - The problem of noncompliance is an increasing and vexing one. Major reasons for this dilemma include a growing skepticism concerning the ability and dedication of the health care industry, as well as a growing population of older people. A review of medical history reveals ancient attitudes toward compliance. There are special problems for special people, such as infants, children, adolescents, elderly persons, and those who are hostile or have a "sick" wish or "death" wish. Persons who require long-term therapy require special care. Child abuse and abuse of elderly persons may be involved. Problems of decreased visual acuity, color perception, and deafness must be dealt with on an individual basis. The responsibility of the physician, which includes nonobtrusive monitoring, is stressed. Consideration is given to the pharmaceutical industry and the role it can play to help mitigate the problem. In conclusion, anticipation of the problem and improved doctor-patient relationships will achieve desired results. PMID- 4025446 TI - Treatment of recurrent vaginal candidiasis. AB - In recurrent vulvovaginal candidiasis, predisposing factors should be eliminated wherever possible. Reduction of the gastrointestinal yeast flora by oral antimycotic treatment does not prevent recurrences. Perianal application of antifungal cream might be an alternative in preventing reinfection from the rectum. Venereal spread of yeasts does not seem to be an important factor, and partner treatment does not significantly alter treatment results. Traditionally, prolonged treatment periods are recommended to prevent recurrences. Patient compliance may then become a factor limiting efficacy. One-dose treatment has been shown to give results that compare favorably with traditional treatment schedules. Results in recurrent cases were comparable with those in primary infections. Thus one-dose treatment could be an acceptable alternative to longer treatment periods in schedules for treatment of recurrent cases. Intermittent prophylactic one-dose application appears to be a promising method of reducing recurrences. PMID- 4025447 TI - Risk factors for complete molar pregnancy from a case-control study. AB - Demographic, reproductive, and dietary histories for 90 white women with complete molar pregnancy were compared in a multivariate analysis with those of 90 parous controls matched to cases by residence, birth year, and race. Women with molar pregnancy were more likely to have been born outside North America (relative risk = 1.9, p = 0.05), were more likely to have been past age 30 at time of their molar pregnancy (relative risk = 1.6, p = 0.05), and were more likely to have diets deficient in the vitamin A precursor carotene. Women with dietary scores for carotene above the control median had a relative risk for molar pregnancy of 0.6 (p = 0.02). In addition, there was a significant trend for decreasing risk for molar pregnancy with increasing consumption of carotene. Although other nutritional deficiencies in patients with complete molar pregnancy may exist, carotene is a biologically plausible candidate for a nutritional risk factor that could explain the geographic distribution of molar pregnancy. PMID- 4025448 TI - Evaluation of the pharmacodynamics and pharmacokinetics of ritodrine when administered as a loading dose. On establishing a potentially useful drug administration regimen in cases of fetal distress. AB - Inhibition of labor during the intrapartum period has been suggested as a method of managing acute fetal distress. In such cases, rapid tocolysis is desirable but, in high doses, beta-adrenergic-receptor agonists, such as ritodrine, may cause severe maternal hypotension that could aggravate the existing fetal distress. We undertook the present study to establish a safe infusion protocol for ritodrine that achieves high plasma concentration rapidly. Twelve nonpregnant female volunteers received, on separate days, three infusions of ritodrine, that is, 1, 2, and 3 mg, during a 2-minute period. The peak plasma concentration measured by high-performance liquid chromatography with electrochemical detection averaged 37, 74, and 100 ng/ml after the 1, 2, and 3 mg doses, respectively. Ritodrine concentrations decreased rapidly and with the 3 mg dose the ritodrine concentration was only 14 ng/ml after 15 minutes. The elimination phase half-life of ritodrine averaged 6.11 hours. None of the doses significantly affected systolic blood pressure but ritodrine increased heart rate and the plasma glucose level and decreased diastolic blood pressure and the plasma potassium concentration. Even at the highest infusion rate, the maximal changes in cardiovascular and metabolic variables were short-lived and clinically modest; heart rate increased 29 bpm, diastolic blood pressure decreased 8 mm Hg, glucose level increased 26 mg/dl, and potassium concentration decreased 0.6 mEq/L. These data indicate that high plasma concentrations of ritodrine can be achieved rapidly without serious side effects. PMID- 4025449 TI - The effect of oral ritodrine therapy on glucose tolerance in pregnancy. AB - Intravenous ritodrine therapy can cause significant deterioration of maternal glucose homeostasis. We investigated the effect of full maintenance oral ritodrine therapy (120 mg/day) on glucose tolerance in the early third trimester with the use of 50 gm 1-hour screens followed by 100 gm 3-hour oral glucose tolerance tests if the screen level was greater than or equal to 140 mg/dl. Four hundred ninety-one patients were studied, 42 of whom were receiving oral ritodrine therapy. Twenty-one percent of the ritodrine-treated women had an abnormal 1-hour screen, which was not different from the 20% observed in women not receiving therapy. None of the treated group and 13% of the untreated group who had abnormal screens had abnormal oral glucose tolerance tests. The probability of an abnormal test after an abnormal 1-hour screen was also determined. PMID- 4025450 TI - Platelets and uric acid in the prediction of preeclampsia. AB - Fifty-four pregnancies that were subsequently complicated by preeclampsia had platelet parameters and uric acid levels measured during pregnancy. The expected fall in platelet count and rise in platelet volume parameters and uric acid levels beyond those that occur in normal pregnancy were seen only in the week before delivery. PMID- 4025451 TI - Modification of fetal intraventricular amniotic shunt. AB - The benefits of fetal intraventricular amniotic shunt remain unknown. Nevertheless, the use of this technique has been described by several authors. One of the potential complications arising from its placement is the inability to retract the catheter once it is placed through the large needle. This communication describes a modification of the shunt procedure. A suture placed through the distal end of the catheter allows retrieval of the catheter shunt for as long as the needle remains in place. PMID- 4025452 TI - Neonatal effects of maternal nadolol therapy. AB - Described is the case of an infant, exposed during gestation to the beta-blocker nadolol, who experienced cardiorespiratory depression, mild hypoglycemia, and growth retardation. The longer duration of action of nadolol and the fact that it is only 30% protein bound make it less desirable than propranolol for use as a beta-blocker during pregnancy. PMID- 4025453 TI - The effect of training in microsurgery. AB - One of the most important and fundamental prerequisites for successful microsurgery is serious and adequate training. This article presents the effect of microsurgical training on the functional end result of reanastomosis in the rabbit fallopian tube and evaluates the appropriate duration of laboratory training. In 50 New Zealand White female rabbits a microsurgical reanastomosis of the fallopian tube in its isthmic portion was performed. The rabbits were divided into five groups. In the first group only 30% of the rabbits conceived on the side operated on. The nidation index was only 0.269 as compared to 0.831 for the control side. Improvement in microsurgical skill following 100 isthmic anastomoses resulted in a 100% pregnancy rate for the last group. The nidation indexes in this group were the same on the side operated on and on the control side, 0.774 and 0.702, respectively. Scanning electron microscopic examination of the anastomosis site revealed a progressive increase in patency rate and in the amount of apposed mucosal folds in the three groups. A training program is recommended, which should bring about a nidation index and pregnancy rate that should not differ from the side operated on to the control side. PMID- 4025454 TI - Effect of isoproterenol on uterine blood flow and cardiac output distribution in pregnant guinea pigs. AB - The effects of isoproterenol, 0.05 micrograms X min-1 X kg-1 infused intravenously for 2 hours, on cardiac output distribution and uteroplacental blood flow were studied in six chronically catheterized guinea pigs between 60 and 68 days of pregnancy. Isoproterenol caused marked cardiac stimulation: Cardiac output was increased by 41%, of which 70% was distributed to the carcass and gastrointestinal tract. Absolute placental blood flow remained essentially unchanged, but the placental fraction of cardiac output decreased from 16% to 11%. Myometrial blood flow increased by 72%. Uteroplacental vascular resistance did not change significantly. In the guinea pig in late pregnancy beta-adrenergic receptors are present in the myoendometrial vessels but could not be demonstrated in the maternal vessels supplying the placenta. PMID- 4025455 TI - Metabolism and disposition of ritodrine in a pregnant baboon. AB - Relatively little is known about the detailed metabolism of ritodrine. The aim of this study was to examine ritodrine metabolism and pharmacokinetics in the maternal and fetal baboon. A fetal-maternal model was made with use of Papio anubis at 144 days of gestation. Tritiated ritodrine was injected as an intravenous bolus into the mother. Maternal and fetal blood samples, amniotic fluid, and maternal urine were collected at time intervals. Samples were analyzed by a combination of high-pressure liquid chromatography and radiochromatography. Conjugated metabolites were recovered and characterized by cleavage studies with use of beta-glucuronidase and sulfatase. The distribution half-life of ritodrine in the mother was 6 minutes and the elimination half-life was 61 minutes. Metabolites were found in both fetal serum and amniotic fluid. The concentrations of ritodrine and its metabolites in fetal serum were at or above the concentrations in maternal serum at 2 hours after maternal intravenous injection. The principal metabolite identified was the sulfate conjugate. The fetus appears to accumulate metabolites. These data indicate that ritodrine crosses the placenta and, in the baboon, achieves levels in the fetus equal to or higher than those in the mother. PMID- 4025456 TI - Endometrial responses to transdermal estradiol in postmenopausal women. AB - In prospective studies, we have determined the endometrial histologic characteristics and patterns of vaginal bleeding in 12 perimenopausal or postmenopausal women during administration of transdermal estradiol, 0.05 mg daily, given either alone or in combination with a progestogen. In the first study, we administered transdermal estradiol in cyclical fashion for 3 months. Outpatient curettage at pretreatment produced no endometrial sample or tissue too scant for assessment from 10 of the 12 patients (83%). At the end of therapy, proliferative or nonsecretory endometrium was diagnosed in nine patients (75%). Eight patients experienced treatment-related vaginal bleeding but no regular pattern, and seven patients reported breakthrough bleeding. Eight patients participated in the second study in which transdermal estradiol was administered continuously and norethindrone, 0.35 mg, was added for 12 days of each calendar month. A further curettage was performed at the end of treatment, and proliferative endometrium was the most common finding. No endometrial hyperplasia was observed. Only one patient experienced breakthrough bleeding. There were no consistent changes with time in the number of patients bleeding each month or in the duration or heaviness of the bleeding. PMID- 4025457 TI - Failure of Lasix to induce a fetal diuresis. PMID- 4025458 TI - Vulvar effects of the toilet tissue observational routine in the practice of natural family planning. PMID- 4025459 TI - Weight-specific stillbirths and associated causes of death: an analysis of 765 stillbirths. AB - An analysis of 765 consecutive stillbirths associated with 98,927 pregnancies during a 6-year interval showed significant differences for cause of death at specific weight categories. In addition, 57% of stillbirths occurred at infant weights of greater than or equal to 1500 gm. Hypoxia accounted for 43% of all stillbirths. The implications with respect to preventability and for changes in routine prenatal care through the incorporation of the several methods of fetal assessment currently available are discussed. PMID- 4025460 TI - Low birth weight, intrauterine growth retardation, and preterm delivery. AB - The relationship between low birth weight, intrauterine growth retardation, and preterm delivery in infants born at a perinatal center is described. Between 20% and 30% of infants born weighing 500 to 2000 gm and nearly 50% of infants born weighing 2001 to 2750 gm had intrauterine growth retardation. For infants within the same low-birth weight group, infants with intrauterine growth retardation had one half to one sixth of the neonatal mortality rate of non-growth-retarded infants. However, only in the 501 to 1000 gm group did the difference in mortality between infants with and without intrauterine growth retardation substantially influence the composition of the group of survivors. PMID- 4025461 TI - Labor and delivery in the presence of mitral stenosis: central hemodynamic observations. AB - During a 1-year period, eight patients with New York Heart Association Class III or IV mitral stenosis were studied throughout the peripartum period with a pulmonary artery catheter. All patients were delivered vaginally. Intrapartum management was based upon cautious diuresis for preload optimization and heart rate control with propranolol. A mean increase in pulmonary capillary wedge pressure of 10 mm Hg was observed in the immediate postpartum period. Only two patients demonstrated a significant increase in cardiac output during this same time period. Central venous pressure correlated poorly with pulmonary capillary wedge pressure in seven of eight patients. Neonatal outcome was uniformly excellent. With the management approach described, no patient exhibited deterioration of cardiopulmonary status during the peripartum period. PMID- 4025462 TI - Practice patterns and attitudes toward education among Canadian obstetricians and gynecologists. AB - A group of 1370 specialists in obstetrics and gynecology were surveyed for information about practice patterns, continuing medical education preferences, and their perception of the adequacy of their own residency training. The overall response rate was 65.7%. More than half were in solo practice, practiced in communities of over 250,000, had been in practice for more than 10 years, or had a full or part-time appointment with a Canadian medical school. A wide range of continuing medical education methods were used. Journals were ranked highest by 41%. It is disturbing that very few physicians (15%) indicated any involvement in practice audit. The quality of residency training was ranked low in a number of areas including genetic counseling, ultrasound, neonatology, intensive care, colposcopy, sexual dysfunction, marital counseling, and hysteroscopy. The survey highlights a number of areas that merit the attention of Canadian programs in postgraduate and continuing medical education in obstetrics and gynecology. PMID- 4025463 TI - The effects of low-dose oral contraceptives on coagulation and fibrinolysis in two high-risk populations: young female smokers and older premenopausal women. AB - A study was undertaken to determine the effect of a low-dose oral contraceptive on the coagulation and inhibitory system of coagulation in 22 young healthy women who smoke and in 15 nonsmoking healthy women between the ages of 34 and 41. Smokers showed statistically significant oral contraceptive-related procoagulant alterations in prothrombin time, thrombin time, and fibrinogen antigen. Antithrombin III antigen and activity were significantly reduced, whereas plasminogen antigen and activity were increased. Inhibitor and fibrinolytic activity was either unaffected or enhanced by oral contraceptives in women over the age of 34: antithrombin III activity was unchanged, plasminogen antigen and activity increased (p less than 0.0007), and alpha 2-antiplasmin was significantly reduced (p less than 0.07). Whereas usage of oral contraceptives in young smokers may initiate biochemical changes in favor of thrombogenesis, their usage in nonsmoking older women enhanced fibrinolysis and had a neutral effect on inhibition and a minimal procoagulant effect. PMID- 4025464 TI - Linkage between the X-linked retinitis pigmentosa locus and the L1.28 locus. AB - Segregation of alleles at the L1.28 locus in members of four informative families with X-linked retinitis pigmentosa was consistent with linkage between the loci for L1.28 and X-linked retinitis pigmentosa. Linkage analysis showed that the best estimate for the recombination distance in these families is 10 centimorgans. When our data are combined with the previously published linkage data, we conclude that the genetic distance between the two loci is 5 centimorgans, or approximately 5 million base pairs of DNA, with a 90% confidence interval of 1.5 to 14 centimorgans. PMID- 4025465 TI - Temporary silicone oil tamponade in the management of retinal detachment with proliferative vitreoretinopathy. AB - Silicone oil was used as a temporary (four to six weeks) tamponade in conjunction with vitreous surgery in the management of 146 eyes with retinal detachment complicated by proliferative vitreoretinopathy. A success rate of 62% (90 of 146 cases) was achieved six months after the silicone was removed. Clinical complications directly related to silicone oil were rare and did not progress or develop after the removal of silicone except for opacification of the lens in phakic eyes. This occurred frequently (43 of 55 eyes) and progressed many months after the withdrawal of silicone. PMID- 4025466 TI - Retinopathy associated with acute pancreatitis. AB - Two patients (a 28-year-old woman and a 23-year-old man) with acute pancreatitis developed severe visual loss. The acute stage of retinopathy consisted of retinal edema, cotton-wool patches, and retinal hemorrhages, predominantly in the posterior pole of both eyes. During the five-year follow-up period, visual acuity improved and sequential fluorescein angiography of both patients demonstrated reperfusion of previously occluded retinal vessels. After resolution of the cotton-wool patches, the previously edematous areas were replaced by foci of retinal thinning which created irregularities in the internal limiting membrane light reflex. Visual fields demonstrated scotomas corresponding to the areas of the previous cotton-wool patches. PMID- 4025467 TI - Ocular toxicity of intravitreally injected liposomal amphotericin B in rhesus monkeys. AB - We determined whether liposome-intercalated amphotericin B was less toxic than commercial amphotericin B when injected intravitreally in the primate. Three rhesus monkeys were studied on each of three occasions. Each eye received increasing doses of amphotericin B (10, 20, or 30 micrograms) or liposome intercalated amphotericin B (40, 80, or 120 micrograms) as a single intravitreal injection. There were often transient inflammatory changes in the anterior chamber and all eyes showed an acute cellular infiltrate in the vitreous humor after injection. These reactions had resolved by eight weeks after injection of the low or intermediate doses of amphotericin B (10 or 20 micrograms) or liposome intercalated amphotericin B (40 or 80 micrograms) but left a mild vitreal infiltrate in the high-dose groups (30 micrograms of amphotericin B or 120 micrograms of liposome-intercalcated amphotericin B). Histologic examination at the end of the third experiment showed no abnormalities. These studies suggest that liposome incorporation reduces the toxicity of amphotericin B by at least fourfold and that as much as 30 micrograms of commercial amphotericin B may be tolerated by the intravitreal route in the rhesus monkey. PMID- 4025468 TI - Comparative toxicity of intravitreal aminoglycoside antibiotics. AB - We compared the toxicity of the aminoglycoside antibiotics (tobramycin, amikacin, netilmicin, and kanamycin) by ophthalmoscopy, light and electron microscopy, and electro-retinography after intravitreal injection in rabbits in doses ranging from 100 to 3,000 micrograms. The earliest manifestations of toxicity were confined to the outer retina with each drug, with lamellar lysosomal inclusions in the retinal pigment epithelium as the earliest finding. However, the aminoglycosides displayed marked differences in the threshold dose required to produce toxic reactions, permitting the following ordering of toxicity: (most toxic) gentamicin greater than netilmicin = tobramycin greater than amikacin = kanamycin (least toxic). PMID- 4025469 TI - Histologic study of a pair of human corneas after anterior radial keratotomy. AB - Two corneas were obtained from a man who underwent anterior radial keratotomy in both eyes less than three months before his death. The corneas were obtained and fixed 16 hours after death and prepared for histologic evaluation four days later. Both corneas showed epithelial ingrowth in the surgical wounds, epithelial inclusion cysts in some areas, and ridges or protrusions of the posterior cornea beneath the incisions. The incisions ranged in depth from 48% to 63% of the full thickness of the cornea in the right eye and from 69% to 98% in the left eye, demonstrating the difficulties involved in maintaining a precise and predictable depth of incision, which may, in turn, be related to variations in visual results. Signs of endothelial stress, in the form of collagen and fibrils on the posterior Descemet's membrane, apparently predated the refractive surgery. Precautions such as specular microscopy may be needed to rule out this kind of surgery in patients with the early signs of some types of potential corneal disease. PMID- 4025470 TI - Topical ketoconazole for fungal keratitis. AB - Six patients (five men and one woman, 19 to 57 years old) with laboratory-proven fungal corneal infections were successfully treated with topical ketoconazole, a synthetic imidazole derivative. No signs of progression of the corneal infection were seen after the antifungal therapy was initiated. The clinical signs of corneal infection disappeared after three (Aspergillus infections) to seven weeks (Fusarium infections) of ketoconazole therapy. In all cases, posttreatment visual acuities were better than pretreatment visual acuities. No significant biomicroscopic signs of ocular surface toxicity were noted. PMID- 4025471 TI - Sequelae of botulinum toxin injection. AB - A total of 136 injections was given to 83 patients for strabismus (99 injections), blepharospasm (29 injections), and spastic entropion (eight injections). All four patients with entropion experienced temporary benefits and early recurrence; one injection resulted in temporary paralytic ectropion. Two of 13 patients treated for blepharospasm developed transient bilateral blepharoptosis. Temporary and related sequelae of extraocular muscle injection included one periocular hemorrhage, one total ophthalmoplegia, and a 44% incidence (29 of 66 patients) of blepharoptosis, which in two patients lasted more than six months. Within three days of injection one patient developed homolateral acute herpes simplex keratitis and a second died of an acute myocardial infarction. No causal relationship for these events has been established. PMID- 4025472 TI - Eyelid suspension with a transposed levator palpebrae superioris muscle. AB - In patients with severe Marcus Gunn jaw-winking, ablation of the synkinetic eyelid movement requires surgical removal of a significant portion of the levator complex (muscle and aponeurosis). As an alternative to removing this tissue completely, the levator muscle can be transected approximately 25 mm above its tarsal plate insertion. The distal levator muscle and aponeurosis can then be used as a suspensory material to suspend the eyelid to the eyebrow. PMID- 4025473 TI - Orbital magnetic resonance imaging. AB - Magnetic resonance images of the eye and orbit performed with surface coils at 1.5 tesla showed anatomic details superior to those of conventional third- and fourth-generation computed tomography. PMID- 4025474 TI - Solitary eosinophilic granuloma of the lateral orbital wall. AB - Two children (aged 18 and 23 months at the initial examinations) were each ultimately found at surgery to have a solitary eosinophilic granuloma of the lateral orbital wall. Both patients had a symptomatic period of six weeks during which time other diagnoses were considered: bacterial preseptal cellulitis and mumps dacryoadenitis in the first case and traumatic recurrent orbital hematoma in the second. Diagnostic difficulties stemmed from confusing features in their histories, as well as the location of the lesion and the deceptively minimal swelling relative to the actual size of the lesion. Follow-up ten and 18 months after curettage of the two lesions showed no recurrence or evidence of systemic involvement. Although most reported cases describe the orbital frontal bone as the site of origin in the orbit, our cases demonstrated that unifocal eosinophilic granuloma may occur in the lateral wall of the orbit. PMID- 4025475 TI - Fresh preparation of subretinal fluid aspirations in Coats' disease. PMID- 4025476 TI - A new polyvinyl alcohol hydrogel as a scleral buckling material. PMID- 4025477 TI - Argon laser iridocorneal adhesiolysis. PMID- 4025478 TI - Combination lens loop-spatula for nucleus delivery during planned extracapsular cataract extraction. PMID- 4025479 TI - Episcleritis associated with familial Mediterranean fever. PMID- 4025480 TI - Laser punctoplasty for the treatment of punctal stenosis. PMID- 4025481 TI - False-normal assays for galactosemia in a neonate with cataracts. PMID- 4025482 TI - Orbital blowout fracture with ipsilateral fourth nerve palsy. PMID- 4025483 TI - Face pain and diplopia in a patient with breast cancer. PMID- 4025485 TI - Conjunctival biopsy in sarcoidosis. PMID- 4025484 TI - Relative afferent pupillary defect in congenital occipital hemianopia. PMID- 4025486 TI - Conjunctival biopsy in sarcoidosis. PMID- 4025487 TI - Physical activity after retinal detachment surgery. PMID- 4025488 TI - Peripheral corneal edema after cataract extraction. PMID- 4025489 TI - Momentary fluctuations of intraocular pressure in normal and glaucomatous eyes. PMID- 4025490 TI - Transition in health care--critical planning for the 1990s: Part One. PMID- 4025491 TI - Reliability of the Behavioral Assessment Scale of Oral Functions in Feeding. AB - Interrater and test-retest reliability of the Behavioral Assessment Scale of Oral Functions in Feeding were computed for two separate samples of severely and profoundly handicapped students having oral-motor and feeding disorders. Reliability was assessed using the intraclass correlation-generalizability theory approach and resulted in coefficients ranging from .68 to .84. These values were considered only marginally acceptable by current standards of instrument development advocated in the behavioral sciences. This paper discusses the difficulty in developing psychometrically satisfactory assessment instruments for use with the severely and profoundly developmentally disabled and gives implications for practice and future research. PMID- 4025492 TI - Examination of selection criteria for a program in occupational therapy. AB - The purpose of this study was to determine if the results of preselection interviews in combination with preselection academic performance offer better predictions of academic performance in occupational therapy than either of these criteria taken singly. The sample consisted of 48 high school students and 31 university students admitted to the program in occupational therapy at the University of Western Ontario from 1978 to 1980. The results indicated that for university students, previous academic performance alone was the best predictor for their performance in first-year occupational therapy. For high school students, the combination of 5 of the 12 interview items with previous academic performance produced the best predictor of successful academic performance in occupational therapy. This implies that for high school students at least, the interview and previous academic performance should both be considered as important selection criteria. PMID- 4025493 TI - Curriculum revision: a case study of the process and product. AB - This paper traces the forces that stimulated a faculty to completely revise its occupational therapy curriculum. The process of the revision, which was largely adapted from a test development model, is recounted. The paper also describes the broad array of teaching/learning methodologies used. Comparative data from the American Occupational Therapy Association Certification Examination indicate that student achievement has significantly improved since the revised curriculum was implemented. PMID- 4025495 TI - Does occupational therapy belong in the university? PMID- 4025494 TI - Gerontic occupational therapy--psychological and social predictors of participation and therapeutic benefits. AB - The purpose of this study was to assess what role psychological and social factors play in predicting the participation of elderly people in a social activation program. Furthermore, the study evaluated the importance of such factors in improving subjects' moods and decreasing feelings of loneliness. Over a six-month period, a social activation program was conducted in a senior citizen apartment building in Stockholm, Sweden. A group of 30 residents from one floor of the building, the experimental group, received the program while a control group of 30 residents from another floor did not. Medical, social, psychological, and behavioral assessments were made immediately before, three months after, and six months after the beginning of the program. Results were that the activity level had increased threefold in the experimental group. Experimental group subjects who initially had a low social activity level and higher scores on the internal-locus-of-control scale had the highest rate of increase in their social activity level. Subjects in the experimental group who initially had a low social activity level, were single or bereaved, scored low on the neuroticism scale, or desired a low level of internal control showed the greatest improvement in mood. Feelings of loneliness decreased the most among those in the experimental group who had a stronger internal locus of control and scored high on pessimistic feelings. Because the program benefited those subjects who initially were the most passive and isolated, it is concluded that gerontic occupational therapy plays an important role in preventing unnecessary social isolation in institutional living. PMID- 4025496 TI - Standardized assessments: ethical principles for use. PMID- 4025497 TI - Prentice Award lecture: a simple retinal mechanism that has complex and profound effects on perception. PMID- 4025498 TI - Binocular summation in man and monkey. AB - Binocular summation, using spatial and temporal modulation sensitivity measurements, has been investigated for human and rhesus monkey observers. In experiments where the refractive errors of both eyes were optimally corrected, the binocular summation functions for both species were similar in magnitude and form, and showed higher summation ratios for temporally modulated stimuli than for spatially modulated stimuli. Monocular retinal image defocus produced a reduction in binocular summation for spatial gratings with the amount of reduction dependent on both the amount of relative defocus and the spatial frequency of the stimulus grating. In contrast, monocular defocus did not effect the magnitude of binocular summation for spatial gratings with the amount for any of the conditions investigated. Over-all, the results of these investigations indicate that binocular summation measures of binocular function may have some advantages over other tests of binocular function that could be utilized in the clinical examination of patients. PMID- 4025499 TI - Tscherning ellipses and ray tracing in ophthalmic lenses. AB - In this paper the exact shape of the solutions to the equations for lenses free of oblique astigmatism, as well as those free from curvature of field or peripheral focus error, are presented. These solutions, as expected, resemble the Tscherning ellipses, but strongly deformed. PMID- 4025500 TI - Tscherning ellipses and ray tracing in aspheric ophthalmic lenses. AB - The effect of conicoid asphericity in one of the surfaces of an ophthalmic lens is examined by means of exact ray tracing. Graphical solutions resembling the Tscherning ellipses are obtained for lenses free of oblique astigmatism as well as for lenses free of peripheral power error or curvature of field. PMID- 4025501 TI - Visual system emmetropia. AB - Based on the fundamental task of the visual system, which is to receive information from the surroundings and to transmit it to the central nervous system, the visual system is described as being emmetropic if the amount of information received through the visual pathways is maximum when the eyes are unaided. A mathematical model of the dependence of the amount of information received through the visual channels on the eye's refractive power and range of clear vision has been worked out. The model, by showing good correlation with common experience, confirms the hypothesis that the amount of information is a coefficient of an eye's approximation to emmetropia and that the criterion of emmetropia of an eye is a particular case of the criterion of emmetropia of the visual system. PMID- 4025502 TI - Prevalence and pattern of adult myopia progression in a general optometric practice population. AB - Longitudinal data on 559 myopic patients were collected from five optometry practices; adequate adulthood refractive data for analysis (three or more visits after 18 years of age) were available for 108 patients. Patterns of refractive change were evaluated subjectively and by linear regression analysis. Most myopes do not progress in young adulthood (about 20 to 25 years of age). Myopia progression during this age period is more common among males than among females. Adulthood myopia progression is related to an increase in corneal power. PMID- 4025503 TI - Tinted hydrogel lenses: an assessment of glare sensitivity reduction. AB - The effect of tinted flexible contact lenses on light sensitivity and photophobic response has often been questioned but never thoroughly investigated. An Alpascope was used to investigate whether tinted hydrogel contact lenses would relieve glare sensitivity in pre-adapted contact lens wearers. Various densities of sky blue and autumn amber Cibasoft hydrogel lenses were used in the study. Analysis of the Alpascope data using the t-test, one-way analysis of variance and Duncan's test showed that there was no reduction in glare sensitivity when tinted contact lenses were worn. PMID- 4025504 TI - Sector pupil dilation with phenylephrine and tropicamide. AB - A comparison of sector pupil dilation produced with 2.5% phenylephrine and 1.0% tropicamide was carried out on nine subjects. We found that 2.5% phenylephrine produced a significant increase in the vertical as compared to the horizontal diameter at 10, 20, 30, 40, and 50 min after instillation of the drug with the maximum vertical diameter occurring at 40 min. The pupil diameter in the vertical and horizontal meridians before drug instillation was 3.7 mm +/- 0.2 (mean +/- SE) whereas at 40 min the vertical and horizontal diameters were 6.7 mm +/- 0.4 and 5.2 mm +/- 0.3, respectively. Instillation of 1% tropicamide produced equal dilation of the vertical and horizontal diameters, which was maximum at 40 min. Before drug instillation, the pupils were 3.7 mm +/- 0.2 (mean +/- SE) in both the horizontal and vertical meridians. At 50 min the pupil diameter was 7.0 mm +/ 0.2 in both meridians in the eye that received tropicamide. PMID- 4025505 TI - Optometry and optometric practices in Nigeria. AB - This paper describes the number, distribution, and characteristics of optometric practices in Nigeria and compares them to similar data in the U.S.A. The results indicate more similarities than differences--the latter attributable to the difference in the age of the profession in the two countries. PMID- 4025506 TI - Clinical note. On the use of salt tablet saline with the Septicon R system. PMID- 4025507 TI - Necrosis of adipose tissue induced by sequential infections with unrelated viruses. AB - Vaccinia virus infection in mice previously infected with and immune to lymphocytic choriomeningitis virus resulted in a clinical illness which neither virus alone induced. The main pathologic finding was extensive fat necrosis with a cellular infiltrate suggestive of delayed type hypersensitivity. Vaccinia virus titers in adipose tissue of clinically ill mice were not higher than those in relevant control groups. This indicates that an unusual virus-induced disease can arise in an animal with a history of unrelated virus infection, and that this disease may be due to an altered host response to infection. The experimental model presented here suggests that chronic inflammation and necrosis of a given tissue may depend on sequential infection with two viruses, neither of which would be capable of inducing such a lesion. PMID- 4025508 TI - Chromogranin-reactive endocrine cells in argyrophilic carcinomas ("carcinoids") and normal tissue of the breast. AB - Breast carcinomas, either positive or negative with the Grimelius' silver procedure, benign fibroadenomas, duct papillomas, and areas of histologically normal breast tissue were tested immunocytochemically with the mouse monoclonal antibody LK2H10 directed against human chromogranin. This is regarded as a general stain for polypeptide-hormone-producing cells and tumors. In 3 of the 9 cases of argyrophilic carcinoma, but in none of 12 ductal infiltrating carcinomas, chromogranin-positive cells were found: the number of reactive cells was very low in 1 case, while in the other 2 carcinomas about 50% of the argyrophilic cells appeared stained. In areas of histologically normal breast tissue, rare argyrophilic chromogranin-positive cells were detected. This study is the first reported evidence concerning the presence of endocrinelike cells probably belonging to the diffuse neuroendocrine system in the normal mammary parenchyma. Our data are consistent with the endocrine nature of at least some of the breast argyrophilic carcinomas. PMID- 4025509 TI - Human aortic fibrolipid lesions. Progenitor lesions for fibrous plaques, exhibiting early formation of the cholesterol-rich core. AB - The early development of the lipid-rich core and other features of atherosclerotic fibrous plaques has been elucidated by examining discrete, small regions of raised intima in human aorta, which often bear a resemblance to both fatty streaks and fibrous plaques. Approximately one-fourth of small raised lesions (less than 16 sq mm of surface area) contained little or no stainable lipid, while three-fourths had a characteristic appearance, which included a superficial layer of foam cells, a core of noncrystalline and/or crystalline lipid, and a developed or developing collagenous cap. Total intimal volumes of the lipid-containing lesions, termed "fibrolipid lesions," ranged from 3 to 43 microliters, with the majority less than 16 microliters. Core lipid in the smallest lesions was located in the musculoelastic layer of the intima. In larger lesions the core extended luminally into the elastic hyperplastic layer, and cholesterol crystals were found more frequently. Total cholesterol concentration in fibrolipid lesions was similar to that in fatty streaks; however, the ratio of unesterified to total cholesterol was relatively high, similar to that found in fibrous plaques. It is concluded that 1) the formation of a lipid-rich core and cholesterol crystallization are early events in the development of many raised lesions; 2) the consistent association between the superficial layer of foam cells and the deep-lying lipid-rich core raises the possibility of an influence, possibly indirect, of foam-cell lipid metabolism on core formation; and 3) the fibrolipid lesion may represent one stage in a potential transitional morphologic sequence between fatty streak and fibrous plaque. PMID- 4025510 TI - Response of the medullary thick ascending limb to hypothyroidism in the rat. AB - Hypothyroidism in the rat is associated with a decrease in kidney size and weight. We have shown previously that this decrease involves all nephron segments in the cortex and outer medulla and is especially pronounced in the medullary thick ascending limb (mTAL). Therefore, the present study was undertaken for examination of the effect of hypothyroidism on the ultrastructure of the rat mTAL. Hypothyroidism was induced by feeding aminotriazole (ATZ), 0.5 g/kg of food, for 4 weeks. A second group of animals received ATZ plus a daily injection of L-thyroxine (T4). A third group was fed a normal diet only and served as control animals. The kidneys were preserved by in vivo perfusion with 3% glutaraldehyde, and tissue from the inner and outer stripe of the outer medulla was processed for electron microscopy. Morphometric analysis revealed a significant decrease in the cross-sectional area of the mTAL in both the inner and outer stripe of the outer medulla in hypothyroid animals. No changes were observed in the surface density of either the apical or basolateral plasma membranes following ATZ treatment. However, when calculated per millimeter tubule, there was a significant decrease in the surface area (SL) of both the apical and basolateral plasma membranes of the mTAL of hypothyroid animals in comparison with control animals. Simultaneous treatment with T4 prevented the ATZ induced reduction in both tubule cross-sectional area and in the SL of the plasma membrane. These findings suggest that the observed changes in SL of the plasma membrane of the mTAL are due to a regulatory role of thyroid hormone in membrane proliferation as well as in cell growth in general. PMID- 4025511 TI - Mesangial proliferative glomerulonephritis associated with progressive amyloid deposition in hamsters experimentally infected with Leishmania donovani. AB - In the present work, 42 golden hamsters (Mesocricetus auratus) were infected by intracardiac injection of 5 X 10(6) amastigote forms of Leishmania donovani. Another group of 28 animals served as uninfected controls. Six hamsters of the infected group and four hamsters of the control group were selected randomly and sacrificed at Days 7, 14, 21, 28, 35, 42, and 49 after inoculation. The kidneys were studied by light microscopy, immunofluorescence and electron microscopy. The levels of serum and urinary immunoglobulins were determined. None of the control hamsters had kidney lesions. Light-microscopically the kidneys of infected hamsters showed a marked mesangial proliferation from Day 7 after infection. These changes were more pronounced at Day 21, when a discrete infiltration of mononuclear cells was frequent. These glomerular changes diminished after Day 28 and were replaced by deposits of amyloid. In the beginning these deposits were in the mesangium and progressively became more extensive, involving capillary loops, Bowman's capsule, and interstitium. The immunofluorescence study showed L donovani antigens and hamster immunoglobulins, primarily in the mesangial areas, by Days 7-14 after infection. These deposits extended into contiguous loops from Day 21 to Day 28. In the last 2 weeks the fluorescent staining for L donovani antigens remained intensely positive, whereas the staining for hamster immunoglobulins became moderate to slightly positive. The ultrastructural study revealed mesangial proliferation, mesangial and paramesangial electron-dense deposits, and amyloidosis in the glomeruli of infected animals. The serum immunoglobulins increased from Day 7 after infection, reaching a peak at Day 21 and falling thereafter until Day 49 to near control values. Immunoglobulins were detected in the urine of infected hamsters at day 21, increasing in amount thereafter. Since L donovani antigens and immunoglobulins were identified in the glomerular lesions, it is likely that they are implicated in the pathogenesis of the mesangial proliferative glomerulonephritis in hamsters experimentally infected with L donovani. The glomerular changes may also explain the loss of immunoglobulins in the urine and the consequent lowering of serum immunoglobulin levels. PMID- 4025512 TI - Chondroclasts in fusarium-induced tibial dyschondroplasia. A histomorphometric study. AB - The role of chondroclasts in the pathogenesis of Fusarium roseum-induced tibial dyschondroplasia (TD) was examined in a histomorphometric study. TD developed rapidly in broiler chickens placed at 1 day of age on rations containing either 3% (Experiment 1) or 2% (Experiment 2) F roseum cultures. In Experiment 1 the frequency of TD in birds killed at 4 weeks of age was 90%. In Experiment 2, birds were killed at intervals from 4 days until 4 weeks of age. By 1 week of age, 70% of birds examined had characteristic accumulations of prehypertrophic cartilage at the proximal tibial physis, and the frequency of TD in 4-week-old birds was 80%. Sections of hypertrophic cartilage from F roseum-fed and control birds from both experiments were examined for determination of the volume density of chondroclasts along the vascular channel boundary. Chondroclast density was consistently lower in F roseum-fed than in control birds, but the difference was significant only at 4 weeks of age. The fact that gross lesions were evident before a significant decrease in chondroclast density occurred indicates that a decrease in the density of chondroclasts was not an essential factor in the accumulation of cartilage characteristic of TD. PMID- 4025513 TI - Animal model of human disease. Dermatomyositis. Familial canine dermatomyositis. PMID- 4025514 TI - Mother-blaming in major clinical journals. AB - The incidence of mother-blaming in major clinical journals was investigated for the years 1970, 1976, and 1982 to determine whether reductions have resulted from the efforts of the women's movement. Very few changes were found across the target years, and mother-blaming was only slightly affected by type of journal and by sex of author. PMID- 4025515 TI - Adoption through the eyes of adult adoptees. AB - This study presents results of a survey of 100 adopted adults who contacted a social service agency or search group. Their perspectives on the experience of adoption and their reasons for agency contact are compared with recommended adoption practice of a generation ago and with reports from the clinical literature. PMID- 4025516 TI - Etiological and prevention views of clinicians with mentally ill relatives. AB - In a survey of 84 experienced mental health professionals with family members suffering from long-term psychotic disorders, more than 70% ranked biogenetic variables as primary, regardless of familial relationship to the patient. Family interactions and parenting were minimized as etiological factors. Biochemical/genetic research, psychopharmacological research, and research on high-risk children were the highest ranked prevention priorities. PMID- 4025517 TI - The fear of needles in children. AB - Encounters with needles are frightening experiences for most young children. This study explores the effect of a single session, cognitively-based intervention program on needle fears in hospitalized children. Results demonstrate significant changes in behavior, heart rate, and pain perception associated with post intervention injection. Implications for routine pediatric practice are discussed. PMID- 4025518 TI - Demographic and educational characteristics of inner city middle school problem absence students. AB - Results of a study of characteristics of middle school students revealed highly significant differences between problem absence students and non-problem absence students on all study variables except sex. Characteristics such as increasing grade, being behind appropriate grade, busing and special education status, and the particular school attended were highly correlated with this behavior, as were race and increasing age. PMID- 4025519 TI - Psychodynamic time-limited groups for adult children of aging parents. AB - A short-term therapy group for adults with aging parents is described. This group model relies heavily on a careful screening process in order to identify individuals best able to focus on intrapsychic issues. The developmental crisis of adult children of aging parents and the beginning process of conflict resolution are illustrated through case material that highlights key psychodynamic issues. PMID- 4025520 TI - When a teacher dies: a school-based intervention with latency children. AB - The behavior and emotional adjustment of latency-age children following the sudden death of their teacher are described. Observational and interview data demonstrate the importance of play and ritual as coping mechanisms. The children's reactions to a replacement teacher, and to expectations that they establish a relationship with the new teacher, are considered. PMID- 4025521 TI - The adolescent incest victim and the judicial system. AB - The effect on the adolescent incest victim of contact with the judicial system is reviewed, and the victim's sense of insignificance, hopelessness, and guilt is noted. A conceptual framework is offered to aid clinicians in their work with incest victims, and suggestions are made for case management. PMID- 4025522 TI - The chronic child patient: ensuring continuity of care. AB - Children under state supervision who are identified as needing long-term psychiatric care often do not have the opportunity to benefit from consistent mental health treatment. The difficulties in establishing a consensus about long term treatment and the problems resulting from an absence of anyone consistently involved with the child over time are illustrated by a case history. Appointment of an "overseer" in such cases is argued for, and guidelines for this role are elaborated. PMID- 4025523 TI - Clinic turmoil and staff transitions. AB - The effects of the July academic rotation on the course of patient treatment in an outpatient clinic were studied. The rotation time was found to be associated with substantial changes in clinic patients' behavior in treatment. The transfer of recent clinic admissions to new therapists was associated with a high rate of dropping out of treatment. PMID- 4025524 TI - The seasonality of schizophrenic births in Alberta. AB - The usual inverse relationship between temperature of month and number of births in that month for persons later given a schizophrenic diagnosis was not found in Alberta, Canada. Since the absence of such an inverse relationship has also been noted in northern Sweden, it is suggested that the atypical pattern in both localities could be a function of the extremely harsh winters. PMID- 4025525 TI - Validity of attention deficit disorder: a second look. PMID- 4025526 TI - Classification and surgical treatment of fibroadhesive otitis. AB - Surgical treatment for fibroadhesive otitis was performed in thirty-seven ears: eight were classified grade 1, with fibrogranulomatous tissue and mucous effusion; twenty-seven were stage 2, with thick fibrogranulomatous tissue without effusion but with cholesterol granuloma. Fifteen ears had small or middle size cholesteatomas, four had posterior retraction pockets. Results obtained were as follow. One stage procedures were usually functional failures in spite of Silastic sheeting, including one tympanoplasty using closed technique with posterior tympanotomy, three dissections of mesotympanum combined with antroatticotomy, and four obliteration procedures in one stage. Better results were obtained with two stage procedures with Silastic sheeting placed at the first stage and removed at the second. Five closed techniques yielded only one good functional result, but seventeen obliteration procedures with Palva flaps yielded the best results: healthy and thin mucosa in fifteen cases, with the mucosa remaining thick in only two cases. Good functional results (air-bone gap less than or equal to 20 dB) were obtained in ten cases, and among them very good functional results (air-bone gap less than or equal to 10 dB) in seven cases. Seven second stages have not yet been done. PMID- 4025527 TI - Surgical treatment of brain herniation into the middle ear and mastoid. AB - A series of thirty-five patients operated on for brain herniation into the middle ear and mastoid is presented. The etiologic factor was felt to be previous surgery in twenty-six cases, head trauma in four cases, chronic otomastoiditis in four cases, congenital dehiscence of the tegmen in one case, and subdural empyema in one case. Diagnosis and treatment of brain herniation are discussed. The mastoid approach for repair of tegmen defects from below with the use of homologous cartilage or autologous cortical bone is advocated. A combined procedure using the transmastoid approach plus a mini-craniotomy of the temporalis squama is suggested as an alternative treatment to middle cranial fossa repair for larger cerebral hernias. PMID- 4025528 TI - Otitis media and the Australian aboriginal. AB - Australia's aboriginal population, which numbers 150,000 persons, suffers much more from otitis media than does the nonaboriginal population, which numbers 15,000,000. Moreover, the clinical presentation, course, and pathology of otitis media in aboriginals have features that differ from what are considered usual. Problems of isolation, communication, and socioeconomic circumstances require that specially designed treatment projects be set up. Debate continues as to why aboriginal otitis media behaves so differently, and theories cover the full range: genetic factors, environment, protein-calorie malnutrition and immunity mechanisms, allergies, different microbiology, and so on. Current research may point up a link to ocular trachoma. The process of spontaneous healing of drum perforations is being studied in an attempt to identify those factors that may delay or prevent such healing. PMID- 4025529 TI - The exenterated mastoid: a problem of ear surgery. AB - The exenterated mastoid behind an intact posterior ear canal wall is one of the preconditions for the development of hidden cholesteatoma recurrences. Retraction pockets can develop into the cavity owing to persisting malfunction of the eustachian tube. Matrix inadvertently left in the tympanic space or in the mastoid process can grow into or in the cavity unnoticed. The way to avoid this nesting site is permanent obliteration of the mastoid process immediately after the eradication of the disease. Furthermore, the disadvantages of old radical operation cavities can be eliminated by secondary obliteration, connected with a revision and repair of the sound pressure transfer mechanism if necessary. It is important to use a nonresorbable obliteration material. We use methacrylate (Sulfix-6) for this purpose, so far without any negative consequences in the ears. PMID- 4025530 TI - "Three cartilages" technique in intact canal wall tympanoplasty to prevent recurrent cholesteatoma. AB - Residual cholesteatoma is the consequence of leaving squamous epithelium in the mastoid and middle ear cleft. It has been demonstrated that the only effective way to reduce the risk of epidermoid cyst neoformation is meticulous and radical removal of cholesteatoma matrix and staging of the operation, regardless of whether a closed or open mastoid cavity tympanoplasty technique has been performed. Recurrent cholesteatoma usually occurs after intact canal wall tympanoplasty secondary to middle ear, attic, and mastoid retraction of the graft, especially in cases with destruction of the scutum or absence of malleus and incus; this is still considered a major problem with this surgical technique. During the last five years we have been performing a procedure we have developed to avoid this retraction. Concave autogenous cartilage from the upper part of the concha auriculae trimmed in three pieces to protect attic, mastoid, and middle ear for graft retraction has been successfully used in 106 surgical procedures. This study describes the surgical technique and analyzes the anatomic and hearing results. PMID- 4025531 TI - Use of autograft and homograft TORP and PORP in the reconstruction of the conductive system in the middle ear. AB - The restoration of a functional transmission system of the middle ear is extremely difficult after a radical operation which leaves a large surgical cavity or in the absence of the tympanic membrane and ossicles, when the window and the tympanic ostium of the tube are covered with thick granulation and fibrous tissue. This article describes my experience in restoring the transmission system of the middle ear combining autograft and homograft with TORPs and PORPs. PMID- 4025532 TI - Does drill noise during mastoid surgery affect the contralateral ear? AB - Drill-generated noise during chronic ear surgery, as well as surgical trauma, has been incriminated as a cause of sensorineural hearing loss in the operated ear. The contralateral ear is subjected to the drill noise but is spared the surgical trauma. Sixty-two patients who had undergone different mastoid operations served as the basis for this study. The average drilling time during surgery was 45 minutes. Sound pressure levels did not exceed 84 dB in the operated ear and 82 dB in the contralateral ear. Though some sensorineural hearing loss was found in the operated ear in fourteen patients, no changes in hearing were found in the contralateral ear. It is suggested that there is no damage exclusively due to the drill noise during mastoid surgery. PMID- 4025533 TI - Residual high-frequency hearing in a patient with Mondini's deformity: clinical implications. AB - We reviewed records of a patient with Mondini's deformity who had hearing loss in the speech frequencies and preservation of hearing for frequencies above 4000 Hz. The patient seemed to be an example of a profoundly deaf child with good speech development secondary to preservation of ultra-audiometric hearing. We suggest that patients with Mondini's deformity have their ultra-audiometric hearing evaluated, and that those with profound deafness and ultra-audiometric hearing be radiographically evaluated to rule out Mondini's deformity for diagnostic and therapeutic purposes. PMID- 4025534 TI - Cholesteatoma with extension to the cochlea. AB - Cholesteatoma invading the membranous labyrinth has been regarded as a serious threat to inner ear function. Thus, a so-called dead ear might be created either by labyrinthine invasion of the cholesteatoma itself or by surgical intervention. A number of reports, however, have contradicted these "established facts," citing patients who have had some degree of hearing in the affected ear before as well as after surgical removal of the cholesteatoma. In the majority of these cases, however, only the vestibular labyrinth was involved, leaving the cochlea unaffected. In the few case reports describing actual invasion of the cochlea, hearing was lost in the affected ear either as a direct consequence of the operation or after an interval of some months. These findings might indicate that the two parts of the inner ear, to some degree, may be functionally separate so that cochlear function could be retained in spite of partial vestibular ablation. We report three cases of intracochlear cholesteatoma. All affected ears had some degree of auditory function before surgical treatment. All three patients presented with partial or total facial nerve palsy on the affected side. After surgery none of the patients had any hearing in the operated ear. The pathophysiologic significance of a functioning cochlea that has been proved to be invaded by cholesteatoma will be discussed. The criteria for correct preoperative management as well as for choice of treatment will also be discussed. PMID- 4025535 TI - Hearing loss with delayed onset of vertigo. AB - The association between the delayed onset of episodic true vertigo and previous sensorineural hearing loss has been previously described. We have reviewed our series of sixty consecutive labyrinthectomies to determine the prevalence of this disorder in this population, and found a variety of etiologic agents of sensorineural hearing loss with subsequent delayed vertigo. Relief from vertigo following surgery has confirmed that the previously deafened ear has been the cause of the vertigo. Case histories are presented and the literature is reviewed. PMID- 4025536 TI - Acoustic neuromas presenting as sudden deafness. AB - Caution is required in diagnosing even apparently "obvious" causes of hearing loss. A patient is described who came to medical attention through referral from a lawyer for sudden deafness allegedly caused by exposure to noise in an industrial setting. Thorough evaluation revealed an acoustic neuroma. Review of the literature suggests that presentation of acoustic neuromas as sudden deafness is more common than generally recognized. Clinicians must be alert to this possibility and diligent in their evaluation of any unilateral ear symptoms. PMID- 4025537 TI - Prognostic implications of therapy for necrotizing external otitis. AB - Necrotizing external otitis is a slowly progressive infection of the ear canal and basal skull caused by Pseudomonas aeruginosa. Treatment with aminoglycoside and antipseudomonal penicillin antibiotics significantly reduces extension of infection, decreases the severity of the associated cranial nerve injury, and limits disease-related mortality. Combined antimicrobial and surgical treatment appears to be more efficacious than antibiotics alone when evaluated for comparable stages of the disease. However, invasive surgical procedures may promote the spread of infection, particularly in the absence of appropriate antibiotic therapy. A high index of suspicion for the syndrome should be aroused when external otitis is present for longer than two weeks, especially after local debridement and topical antibiotic treatment. Aggressive use of systemic antibiotic therapy in diabetic patients, who are at greatest risk, should reduce disease extension and lessen the need for multiple surgical procedures. PMID- 4025538 TI - Ketone body metabolism in normal and diabetic human skeletal muscle. AB - Although the liver is considered the major source of ketone bodies (KB) in humans, these compounds may also be formed by nonhepatic tissues. To study this aspect further, 3-[14C]hydroxybutyrate (BOH) or [3-14C]acetoacetate (AcAc) were constantly infused after a priming dose and contemporaneous arterial and venous samples were taken at splanchnic, heart, kidney, and leg sites in eight normal subjects (N) undergoing diagnostic catheterization and at the forearm site in five normal and six ketotic diabetic (D) subjects. After 70 min of infusion, tracer and tracee levels of AcAc and BOH reached a steady state in the artery and vein in both normal and diabetic subjects. The venous-arterial (V-A) difference at the forearm step for cold KB was negligible both in normal and diabetic subjects, whereas for labeled KB it was approximately 10-fold higher in diabetic subjects (V-A AcAc, -31 +/- 7 and -270 +/- 34 dpm/ml in N and D, respectively; V A BOH, -38 +/- 6 and -344 +/- 126 dpm/ml in N and D, respectively). We assumed that the V-A difference in tracer concentration was consistent with dilution of the tracer by newly synthesized tracee inside the muscle and calculated that the forearm muscle produces KB at a rate of 16.2 +/- 3.3 mumol/min in D and 0.9 +/- 0.9 mumol/min in N. These findings can be accounted for by the hypothesis that the disappearance flux of KB from circulation was replaced by an equivalent flux of KB entering the vein at the muscle step in D but not in N. Moreover, in N KB were not only produced but also utilized by the splanchnic area (39 +/- 9 mumol/min).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4025539 TI - Cardiovascular responses to parathyroid hormone. AB - The synthetic amino terminal fragment of parathyroid hormone, PTH-(1-34), is a potent coronary artery vasodilator in the dog. In the present study, using instrumented open-chest dogs, we have performed the initial characterization of this effect and showed other dose-related cardiovascular effects of the hormone. A near-maximal flow response was obtained after intracoronary injection of 0.024 nmol X kg-1 PTH-(1-34) with minor, if any, concomitant changes in mean blood pressure, contractile force, or heart rate. At higher doses, mean blood pressure decreased while contractile force and heart rate increased in dose-dependent fashion. Infusion of PTH-(1-34) for 20 min showed that the vasodilatory effect could be sustained without a concomitant decrease in mean arterial pressure. Pharmacological characterization showed for the first time that the coronary response to PTH-(1-34) was unaltered in the presence of beta- or alpha adrenergic, muscarinic, or histaminergic blockades. We conclude that PTH-(1-34), an endogenous circulating calcemic peptide, produces a large increase in coronary blood flow at doses sufficiently low to preclude complicating effects on blood pressure, contractile force, and heart rate. Furthermore, the results suggest that the vasodilatory effects may be specific. PMID- 4025540 TI - Responses and molecular heterogeneity of IR-GIP after intraduodenal glucose and fat. AB - The plasma responses and molecular heterogeneity of human immunoreactive gastric inhibitory polypeptide (IR-GIP) after intraduodenal administration of equicaloric amounts of glucose (25 g) and fat (10 g) were determined with five different antisera. Two of these do not cross-react with 8 kdaltons (kDa) IR-GIP. In the fasting state plasma IR-GIP concentrations were highest measured with antisera, which detected both 5 and 8 kDa IR-GIP. The total integrated or incremental IR GIP areas were similar after glucose and fat when determined with the same antiserum. When antisera with similar cross-reactivity with human 5 kDa IR-GIP were compared, no difference in incremental IR-GIP areas after either stimulus was found between antisera that did and did not measure 8 kDa IR-GIP. Gel filtration of plasma showed a consistent increase in 5 kDa IR-GIP 60 min after both glucose and fat but small and inconsistent changes in 8 kDa IR-GIP. Thus fat on a weight and molar basis is more potent than glucose in releasing IR-GIP. Both fat and glucose release predominantly the 5 kDa IR-GIP. Although of importance for the absolute IR-GIP level in plasma, 8 kDa IR-GIP contributes little to the increase in IR-GIP after both stimuli. PMID- 4025541 TI - Hypertension during chronic peripheral and central infusion of angiotensin III. AB - Recent studies have suggested that the angiotensin II (ANG II) metabolite [Des Asp]ANG II (ANG III) may be nearly equipotent with the parent compound in causing several acute neural responses known to be stimulated by angiotensin peptides (i.e., drinking, augmentation of sympathetic neurotransmission, and centrally mediated pressor responses). Because neural actions of ANG II are thought to contribute importantly to the ability of this hormone to cause chronic hypertension, the purpose of the present experiments was to explore the cardiovascular effects of chronic administration of ANG III either into the bloodstream or directly into the brain via the cerebral ventricles. The neurogenic component of the pressor response to acute infusion of ANG III also was reinvestigated. In anesthetized pithed rats (n = 6) ANG III had only 10% of the pressor potency of ANG II when given by acute (5-10 min) intravenous infusion. In conscious rats (n = 5) ANG III had 25% of the pressor potency of ANG II when tested using acute intravenous administration. The acute intravenous pressor potency ratio in conscious versus pithed rats was 4.8 for ANG III and 1.1 for ANG II, suggesting that, compared with ANG II, the pressor response to ANG III shows a greater dependence on neurogenic mechanisms at the doses tested. Chronic (5-day) intravenous infusion of ANG III (at 10, 20, and 100 ng/min) caused sustained hypertension without changes in fluid/electrolyte balance, but only at a dose (100 ng/min) estimated to produce blood levels of ANG III well beyond the "physiological" range.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4025542 TI - Regulation of iodothyronine 5'-deiodination in lean and obese (ob/ob) mice. AB - Obese (ob/ob) mice exhibit impaired cold- and diet-induced thermogenesis, which may result in part from a defect in thyroid hormone action at the level of peripheral deiodination of thyroxine (T4) to 3,5,3'-triiodothyronine (T3). The latter possibility was examined by comparing kinetic parameters of 5' deiodination (5'-D) in hepatic and renal microsomes of lean and obese mice during various physiological conditions. 5'-D Was adaptive to changes in age (1 to 8-10 wk), environmental temperature (14, 25, and 33 degrees C), and thyroid hormone status in both lean and obese mice. The magnitude of enzyme response, however, varied between phenotypes. 5'-D Response to age and environmental temperature was also dependent on tissue type, indicating that different isozymes for 5'-D may exist in liver and kidney. Under basal conditions at 25 degrees C, maximal hepatic and renal 5'-D was lower in obese mice than in lean mice. Differences in Vmax were observed as early as 1 wk of age. Km values for 5'-D were similar in lean and obese mice. These findings suggest that T3 availability to thermogenic target tissues may be impaired in obese mice, which may contribute to diminished thyroid hormone expression and heat production in these animals. PMID- 4025543 TI - Hydration of fat-free body in protein-depleted patients. AB - It is widely believed that increased hydration of the fat-free body accompanies most major disease processes as a result of contraction of the body cell mass and expansion of the extracellular fluid. Measurements of total body water (TBW) and total body nitrogen in 68 normal volunteers and 95 surgical ward patients presenting for intravenous nutrition have been used to derive ratios of TBW to fat-free mass (TBW:FFM) and protein indices (PI), where PI is defined as the ratio of measured total body protein to predicted TBP. Mean values of PI were 1.009 +/- 0.116 (SD) and 0.783 +/- 0.152 in the normal and patient groups, respectively, corresponding to mean TBW:FFM ratios of 0.719 +/- 0.016 and 0.741 +/- 0.029. However, 48 patients had normal TBW:FFM despite having lost 15% of body protein. A theoretical model of body composition changes in catabolic illness is presented, which is in accord with the patient data, demonstrating that TBW:FFM does not necessarily increase in catabolic illness and that the ratio masks underlying shifts in body fluid compartments. PMID- 4025544 TI - Role of small intestine in pathogenesis of hyperlipidemia in diabetic rats. AB - The small intestine can utilize endogenous substrates for triglyceride synthesis. In diabetes mellitus, potential endogenous substrates are elevated. This study was designed to investigate whether intestinal triglyceride production utilizing endogenous substrates contributes to the pathogenesis of hyperlipidemia in diabetes. Intestinal fatty acid esterification as well as activities of acyl-CoA synthetase and acyl-CoA monoglyceride acyltransferase are the same in diabetic and control rats when the results are expressed per milligram protein. However, due to marked intestinal hypertrophy these activities are increased when the results are expressed as per centimeter gut length. In the mesenteric lymph fistula rat model, we found that during fasting diabetic rats have a greater than twofold increase in triglyceride output that is carried mainly by very low density lipoproteins (VLDL). During lipid infusion, total triglyceride fatty acid output was not different between diabetic and control rats, although there were significant differences in the patterns of partition of endogenous and exogenous triglyceride into chylomicrons and VLDL. Endogenous triglyceride production did not increase in diabetic rats during lipid infusion. In contrast, there was a substantial increase in endogenous triglyceride production in the control group to a level comparable with that of the diabetic rats. There was a significant reduction in incorporation of exogenous triglyceride into chylomicrons in diabetic rats. PMID- 4025545 TI - Phosphate transport in intestinal brush-border membrane vesicles: effect of pH and dietary phosphate. AB - Phosphate transport was investigated in brush-border membrane vesicles prepared from the duodenal segment of the chicken small intestine. Phosphate transport was sodium dependent and demonstrated the typical overshoot phenomenon with an external sodium gradient. There was no appreciable difference in phosphate uptake rates at pH 6.5 or 7.5 values, and the apparent kinetic parameters suggested that both the monovalent form, H2PO4-, and divalent form, HPO4(2-), were transported at the appropriate pH values. The apparent Km values were 0.10 and 0.07 mM, respectively. Determination of the sodium stoichiometry, assessed by an external sodium concentration or by the static-head method, suggested an interaction of one or more sodium ions with phosphate at the acid pH value and two or more sodium ions with phosphate at the alkaline pH value. The sodium affinity for sodium-dependent phosphate transport was in the order of 10-25 mM and was similar at both pH values. Phosphate accumulation was not affected by an externally applied potassium diffusion potential, suggesting an electroneutral process at both pH values. The cumulative evidence would suggest Na+-H2PO4- transport at pH 6.5 and 2Na+-HPO4(2-) at pH 7.5 value, and the effect of hydrogen ions on sodium dependent phosphate transport is dependent on the external sodium concentration. Brush-border membranes isolated from chickens maintained for 5-7 days on a low phosphate diet demonstrated a greater sodium-dependent phosphate uptake (Vmax) than animals on normal phosphate intakes with no change in the apparent Km. Sodium stoichiometry and the rheogenic nature of the process appear to be similar to those present in normal birds.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4025546 TI - Effect of ethanol on choline transport in rat jejunum. AB - The effect of ethanol on choline transport across the rat jejunum was studied by intraluminal perfusion in vivo and by influx measurement across the brush-border membrane in vitro. Acute ethanol administration (4 g/kg) through a gastric tube caused an increase in net choline absorption within 1 h. The increase was prevented by pretreatment with pyrazole, an inhibitor of ethanol metabolism. Chronic ethanol administration also caused an increase in choline absorption, the effect being unrelated to the nutritional changes that occur with ethanol ingestion. In contrast, direct instillation of 0.65 M ethanol through the perfusate caused no changes in choline absorption, and the perfusion of a 1.14 M solution even decreased absorption. The in vitro influx of choline across the mucosal membrane of the isolated rat jejunum was also enhanced by pretreatment with ethanol given by gavage 1 h prior to experimentation. Similarly, the ethanol related increase in the influx rate was inhibited by pyrazole but was unaffected by acetaldehyde or acetate. Like ethanol, pretreatment of rats with methanol stimulated the choline influx rate. The results suggest that ethanol metabolism, rather than the direct effect of ethanol by itself, stimulates the absorption and influx of choline into the rat jejunum. The effect is not produced by the primary metabolites of ethanol, acetaldehyde, or acetate but is very likely related to stimulation by other products of ethanol metabolism. PMID- 4025547 TI - Effect of lactation on cholesterol synthesis in rats. AB - Lactation induces a variety of morphological and functional changes in the gastrointestinal tract. In the present study we employed tritiated water as the substrate to demonstrate that in the intact rat lactation results in a twofold increase in cholesterol synthesis in the small intestine. Feeding a high cholesterol diet did not markedly inhibit small intestinal cholesterol synthesis in either control or lactating animals, and the difference in cholesterol synthesis between the two groups persisted. In the large intestine, cholesterol synthesis is increased threefold in the lactating animals, and feeding a high cholesterol diet did not affect synthesis in either the control or lactating animals. In the liver, lactation stimulated cholesterol synthesis, and quantitatively this increase in hepatic cholesterol synthesis is much greater than the increase observed in the intestines. Feeding the rats a high-cholesterol diet markedly inhibited hepatic cholesterol synthesis in both control and lactating animals, a finding that demonstrates that the feedback inhibition of cholesterol synthesis in the liver is not impaired by lactation. In the lactating animals, the quantity of labeled cholesterol in 1 ml of serum is 2.4 times greater than observed in controls. Feeding the rats a high-cholesterol diet markedly decreased the quantity of labeled cholesterol in the serum in both groups and obliterated the difference between control and lactating animals. This suggests that the increased hepatic cholesterol synthesis in the lactating animals is responsible for the differences in labeled cholesterol in the serum. Cholesterol feeding also reduced the quantity of labeled cholesterol localized to the mammary glands in lactating animals.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4025548 TI - Duodenal aluminum absorption in the rat: effect of vitamin D. AB - Aluminum absorption by the duodenum was studied with an in vivo isolated gut segment technique in vitamin D-deficient and vitamin D-replete rats. Aluminum uptake could be resolved into saturable and nonsaturable components. Both groups demonstrated an identical nonsaturable mechanism with an aluminum uptake of approximately 23% of the amount perfused per 100 mg dry intestinal weight. Saturable absorption was significantly lower in the vitamin D-deficient group (Jmax 6.9 +/- 1.4 microM X h-1 X 100 mg dry wt-1) than in the vitamin D-replete group (Jmax 13.0 +/- 2.7 microM X h-1 X 100 mg dry wt-1) (P less than 0.05). The presence of aluminum in the perfusion solutions reduced duodenal calcium absorption by 33% (P less than 0.02) in the vitamin D-replete group but not the vitamin D-deficient group. These results suggest that aluminum is absorbed in the duodenum by both a nonsaturable mechanism and a vitamin D-dependent saturable mechanism, for which it may compete with calcium. PMID- 4025549 TI - Characterization of segmental collateral blood flow in the small intestine. AB - Collateral blood flow and the pressures and resistances determining that flow were measured between two adjacent segments of canine jejunum following acute occlusion of the arterial branch perfusing one of the segments (the "recipient" segment). Collateral flow was approximately 55% of control flow in the recipient segment. This flow was provided by an equal increment in arterial flow to the nonischemic ("donor") segment, such that pressures, resistances, and flows in the donor segment were not affected. Virtually all of the total collateral flow was derived from precapillary channels and was therefore available to the capillary bed of the recipient segment. Collateral flow was adequate to maintain the recipient segment in a nonischemic state, as indicated by the absence of a reactive hyperemia following release of the arterial occlusion. Selective occlusions of intramural or extramural collateral channels indicate that about two-thirds of the total collateral flow is derived from the extramural (marginal) vessels, while the remainder is supplied by intramural collaterals. For the most part collateral flow between adjacent segments is determined simply by the pressure gradient between connecting collateral channels. PMID- 4025550 TI - Effects of temperature on ileal blood flow and oxygenation. AB - Arterial pressure, venous outflow pressure, blood flow, and arteriovenous oxygen difference were measured in autoperfused preparations of canine ileum while lumen temperature was altered in 1-5 degrees C increments (or decrements) between 31 and 40 degrees C. Neither blood flow nor vascular resistance was correlated to lumen temperature. However, both arteriovenous oxygen difference and oxygen uptake were linearly correlated with lumen temperature. The relation between ileal oxygen uptake and lumen temperature was consistent with a change in metabolic rate for a 10 degrees C change in temperature (Q10) for oxygen consumption of 2.7. These observations indicate that ambient temperature exerts a profound influence on intestinal oxygen consumption and that variations in temperature may explain the wide range of intestinal oxygen uptake values reported in the literature. PMID- 4025551 TI - Postprandial regulation of intestinal blood flow: role of gastrointestinal hormones. AB - Systemic arterial pressure, jejunal perfusion pressure, and jejunal blood flow were measured in eight autoperfused canine jejunum preparations (5 dogs) before and during local intra-arterial infusion of physiological doses of secretin (18.5 pM), neurotensin (233 pM), and cholecystokinin octapeptide (CCK-8, 30 pM). Intra arterial infusion of secretin, neurotensin, or CCK-8 alone did not affect either systemic or jejunal arterial pressures. Likewise, jejunal blood flow was not significantly altered by secretin (3 +/- 3%), neurotensin (-5 +/- 4%), or CCK-8 ( 5 +/- 5%). Even when all three hormones were infused simultaneously, jejunal blood flow was not altered (2 +/- 3%). However, when infused at rates that produced calculated arterial blood levels some 100 times greater than those reported as "postprandial," each hormone alone, as well as in combination, produced marked increases in jejunal blood flow. Secretin, neurotensin, and CCK-8 increased blood flow by 34 +/- 8, 31 +/- 11, and 24 +/- 5%, respectively. Simultaneous infusion of all three hormones increased jejunal blood flow by 47 +/ 11%. These data suggest that, either alone or in combination, secretin, neurotensin, and CCK-8 are not of quantitative importance in regulating jejunal blood flow during the postprandial state. However, higher (presumably pharmacological) blood levels of these hormones do significantly elevate jejunal blood flow. PMID- 4025552 TI - Contractile patterns and transit of fluid in canine terminal ileum. AB - Earlier recordings of intraluminal pressure from the terminal ileum and across the ileocolonic sphincter of dogs revealed, in addition to the usual interdigestive and digestive patterns, pressure waves that appeared to have propulsive potential. One of these, which we designated as a "prolonged propagated contraction" (PPC), was a wave of high amplitude; it had a duration much longer than the ileal slow wave and migrated rapidly through the ileum, often into the proximal colon. The other pattern was one of "discrete clustered contractions" (DCC); these were propagated bursts of rhythmic phasic waves, distinct from phase III of the interdigestive myoelectric complex. These migrated through the ileum more rapidly than did phase III. Our aims were to record the electrical and mechanical equivalents of these pressure events using only extraluminal sensors and to evaluate the capacity of these contractions to propel fluids. PPCs and DCCs were recorded by extraluminal strain gauges, and flow was assessed by recovery of a nonabsorbable marker. Phase III of the migrating motor complex propelled fluid through the ileum, but in addition DCCs and, especially, PPCs were able to empty the ileum. These latter contractions have similarities to the ileal "peristaltic rush" described by others, and we believe these waves are an important force for ileal emptying. PMID- 4025553 TI - Renal handling of aluminum in the rat: clearance and micropuncture studies. AB - Previous uncertainty regarding glomerular ultrafilterability (UF) of aluminum has limited the definition of renal Al handling. Glomerular micropuncture was therefore performed in hydropenic Munich-Wistar rats infused with AlCl3 to achieve plasma (P) Al levels between 2 and 10 mg/liter. Glomerular fluid, P, and urine Al concentrations were measured by flameless atomic-absorption spectrophotometry. UFA1 was inversely correlated with PA1 [%UFA1 = 10.3 - 8.4 (log PA1), r = -0.90, P less than 0.01]. When this equation was used to calculate the filtered load (FLA1), A1 excretion (UA1V, ng/min) in simultaneously collected samples was found to be a direct function of FLA1 [UA1V = 5.7 + 0.37 (FLA1), r = 0.93, P less than 0.01]. Fractional excretion (FE) of A1 was 39.4 +/- 4.2% in these hydropenic experiments (FENa = 0.3 +/- 0.1%). We next evaluated the tubular handling of A1 (using these UF data) during step-wise extracellular fluid volume expansion with isotonic saline (2.5, 5.0, 7.0, and 7.0% body wt) and during the infusion of increasing doses (2.7, 5.3, 8.0, and 8.0 mg X kg-1 X h-1) of furosemide as urinary losses were quantitatively replaced. The natriuresis produced by volume expansion (FENa = 1.0, 3.0, 8.4, and 7.9%) and furosemide (FENa = 4.2, 6.0, 6.6, and 6.7%) were comparable. At similar FLA1, 7% volume expansion but not furosemide (at any dose) increased UA1V (240 and 95 ng/min, respectively, vs. 116 ng/min in hydropenia) and FEA1 (84.5 and 29.4 vs. 37.4%, respectively). These data indicate that at pharmacological PA1 levels, less than 8.4% of PA1 is ultrafilterable, suggesting extensive plasma protein binding.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4025554 TI - pH regulation of endogenous acid production in subjects with chronic ketoacidosis. AB - In a previous study of starvation-induced acute ketoacidosis, net ketoacid production was inhibited by acid and facilitated by base ingestion. To determine whether hydrogen ion modifies net ketoacid production during chronic ketoacidosis, six over-weight volunteers ingested NaHCO3, NaCl, or NH4Cl (2 mmol X kg-1 X day-1), each for 7 days, during weeks 6-8 of ketogenic dieting. During days 4-7 of each phase, blood bicarbonate was stable but lower in the NH4Cl (19.6 +/- 0.7 mM) than the NaHCO3 (23.7 +/- 0.7 mM) phases. Throughout these periods, acid intake differed by 216 mmol/day, whereas acid output differed by 129 mmol/day between the NaHCO3 and the NH4Cl phases. The major contribution to this difference in acid balance was a difference in net organic acid (ketoacid) production. Although blood ketones were stable, ketoacid excretion, reflecting net ketoacid production, was decreased by 59% with acid and increased by 66% with base compared with NaCl (control) ingestion. Thus, in this state of chronic ketoacidosis, challenges to acid-base balance were countered by a rapidly occurring, sustained, reversible, and quantitatively significant modification of net acid production which acted as an effective mechanism for acid-base regulation. PMID- 4025555 TI - Effects of KCl infusion on potassium excretion in sheep. AB - To determine the quantitative relation of K excretion (UKV) to plasma K concentration (PK), three fasted, conscious, mature ewes were infused intravenously with 50 mmol KCl over 15, 30, and 60 min. Control experiments were without infusion. During KCl infusion PK was increased to 7.26 +/- 0.40 (15 min), 6.68 +/- 0.48 (30 min), and 5.59 +/- 0.3 meq/liter (60 min). During all three infusions the increase in UKV relative to the increase in PK was similar. The mean delta UKV/delta PK ratio was 160 +/- 30 (SD) mueq/min per meq/liter (range 102-203). On termination of each infusion PK decreased to control values, but UKV either remained elevated (60-min infusion) or first decreased and then increased (15- and 30-min infusions). The second, delayed kaliuresis began 30-45 min after initiation of KCl infusion and accelerated a return to the level of K balance of the control experiments. A plot of UKV against the corresponding period PK showed that, at a common value of PK, UKV was higher following KCl infusion when PK was dropping than during KCl infusion when PK was rising. The mechanisms responsible for this hysteresis phenomenon are not identified. PMID- 4025556 TI - Effects of dDAVP on rat juxtamedullary nephrons: stimulation of medullary K recycling. AB - The effects of 1-desamino-8-D-arginine vasopressin (dDAVP) on the handling of water and electrolytes by the juxtamedullary nephrons were studied on rats with reduced circulating levels of antidiuretic hormone (ADH), parathyroid hormone, calcitonin, and glucagon, all of which stimulate the adenylate cyclase system of the thick ascending limb and the distal tubule. In such hormone-deprived rats and in hormone-deprived + dDAVP rats, the concentration of Na, Cl, and total solutes was lower in the ascending than in the descending limbs, whereas the inulin concentration was similar at both sites. dDAVP did not alter the fraction of NaCl remaining in the thin limbs, but tended to reduce that of Mg and Ca. On the other hand, dDAVP significantly increased the fraction of filtered K remaining from 65.8 +/- 5.2 to 107.3 +/- 15.8%. A direct correlation was observed between the fraction of filtered K remaining at the tip of the juxtamedullary loops and the fractional excretion rate of K in urine. Since dDAVP enhances distal K net secretion, as previously shown in our laboratory, these results indicate that the medullary recycling of K from nephron terminal segments to Henle's loop of juxtamedullary nephrons is stimulated by this peptide. PMID- 4025557 TI - Water and electrolyte transport in Henle's loop and distal tubule after renal sympathectomy in the rat. AB - The effect of acute renal denervation (AD) on transtubular movement of water and electrolytes in Henle's loop (LH) and distal tubule (DT) of superficial nephrons was studied by the technique of in vivo microperfusion in Inactin-anesthetized hydropenic male rats. In time-control experiments (n = 6) no changes in either whole kidney or single nephron function were detected. Predenervation results of denervation experiments (n = 10) were similar to those of the time-control series. AD resulted in increased urine, sodium, and potassium excretion in the absence of changes of either arterial blood pressure or GFR. Compared with predenervation data, AD led to significant decreases in net transtubular fluxes (J) of water and sodium in both perfused segments with delivery kept constant (delta JNa: LH = 144 +/- 26 peq X min-1, 9.1 +/- 0.3%; DT = 94 +/- 11 peq X min 1, 22.3 +/- 1.1%). Potassium absorption in the loop decreased but an increase in net addition (secretion) of K in the distal tubule on denervation occurred (delta JK = 8.7 +/- 1.9 peq X min-1, 68.7 +/- 3.2%). Use of the reperfusion technique gave similar results. These results indicate that efferent renal sympathetic nerve activity directly influences water, sodium, and potassium transport in the loop of Henle and distal tubule of the anesthetized rat. PMID- 4025558 TI - Importance of the liver during glucagon-mediated increases in canine renal hemodynamics. AB - We ascertained the importance of the liver in mediating glucagon-induced increases in renal blood flow (RBF) and glomerular filtration rate (GFR) by comparing the renal hemodynamic responses to intrarenal versus intraportal infusion of glucagon at 3 ng X kg-1 X min-1 (a dose previously considered "physiologic") in two separate sets of anesthetized dogs. Following intrarenal infusion for 60 min (n = 6), glucagon was without effect on RBF and GFR. On the average, RBF and GFR increased by only 2 +/- 1 and 3 +/- 1%, respectively. However, in a second group of dogs (n = 6), intraportal infusion of glucagon significantly increased both RBF and GFR by the same order of magnitude over 60 min. RBF and GFR increased, on the average, by 22 +/- 2 and 20 +/- 2%, respectively. Peak responses occurred 30 min following glucagon infusion when RBF and GFR were elevated by 25 +/- 2 and 26 +/- 2%, respectively. In neither group of dogs were filtration fraction, arterial pressure, heart rate, arterial hematocrit, or arterial plasma protein concentration altered. These data indicate that the liver plays an important role in mediating the renal hyperemia and hyperfiltration observed following a physiologic infusion of glucagon. PMID- 4025559 TI - Responses of the atrial myocardium to cardiac sympathetic nerve stimulation. AB - The cardiac responses to sympathetic nerve stimulation were measured in open chest, anesthetized dogs before and after infusions of cocaine, which were given to inhibit the neuronal uptake of norepinephrine. Cocaine did not augment the inotropic or chronotropic responses, but it did retard their decay after cessation of sympathetic stimulation. Before cocaine, the half-times for decay of the chronotropic, atrial inotropic, and ventricular inotropic responses were 28.4 +/- 2.2, 29.8 +/- 2.7, and 22.1 +/- 1.9 (+/- SE) s, respectively. After cocaine, however, the half-times were significantly greater (147 +/- 12.0, 51.4 +/- 3.9, and 32.9 +/- 2.5 s, respectively). The cocaine-induced prolongation of the decay time in a given cardiac tissue is a measure of the relative efficacy of neuronal uptake as a mechanism for dissipating the neurally released norepinephrine. Our data indicate, therefore, that among the various cardiac tissues that we studied, the neuronal uptake mechanism is least effective in the ventricular myocardium, somewhat more effective in the atrial myocardium, and most effective in the sinoatrial nodal region. PMID- 4025560 TI - Nonuniformity of inner and outer systolic wall thickening in conscious dogs. AB - Transmural differences in systolic wall thickening were analyzed in 13 conscious dogs by implanting sonomicrometers to continuously measure total wall thickness (WT) and outer WT approximately half the distance through the myocardium at a closely adjacent location. Inner WT was derived by subtraction of outer WT from total WT. Outer wall measurements spanned, on average, the outer 44 +/- 10% (+/- SD) of the wall; derived inner wall measurements spanned the remaining 56 +/- 10%. At rest the fractional contribution (FC) of the outer wall to total systolic wall thickening was 29 +/- 9%, which was significantly less than the FC of the inner wall, 71 +/- 9%. These data are in good agreement with simplified modeling of a cross section of the left ventricle as two concentric rings that predicts that the FC of inner and outer halves of the wall should be approximately 67 and 33%, respectively. During treadmill exercise, the extent of both inner and outer thickening increased significantly (30 and 29%, respectively) but the relative FC of the inner and outer wall remained the same. The data indicate that systolic wall thickening is nonuniform and that this nonuniformity remains constant during the increased inotropic and chronotropic stimulation associated with exercise. PMID- 4025561 TI - Effect of pacing on oxygen supply-to-consumption ratio in ischemic myocardium. AB - This study was performed to determine if the partially occluded myocardium could maintain its O2 supply-to-consumption ratio during atrial pacing. In 14 open chest anesthetized dogs, the left anterior descending coronary artery was occluded to 50% of base-line flow, and in half of the dogs the hearts were paced to 50% above base-line heart rate. Blood flows were determined by use of microspheres before and after occlusion, and O2 supply-consumption variables were determined by use of microspectrophotometry. After occlusion in control and paced groups, blood flow was depressed in the ischemic region compared with the nonischemic region. In paced animals, blood flows in all regions were significantly higher compared with their respective values in nonpaced animals. After pacing, mean O2 consumption was 34% higher (53% in the occluded region) compared with control animals. The O2 supply-to-consumption ratio was similar in the occluded region of paced animals compared with the same region in controls. This ratio was lower in ischemic regions of both groups compared with their respective nonischemic regions. This indicates that, despite a reduced O2 supply to-consumption ratio in the ischemic area, an unutilized reserve of flow exists. PMID- 4025562 TI - Intracoronary naloxone in hemorrhagic shock: dose-dependent stereospecific effects. AB - Treatment with naloxone improves cardiovascular function and survival in a variety of shock models, and numerous sites and mechanisms for its action have been proposed. Data presented in this article support the hypothesis that in hemorrhagic shock naloxone exerts its beneficial hemodynamic effects by acting primarily at cardiac opiate receptors. Naloxone or its stereoisomer (d-naloxone) were administered intravenously (iv) and directly into the coronary circulation (ic) in dogs anesthetized with pentobarbital sodium and subjected to hemorrhagic shock. Treatment with naloxone (2.0 mg/kg iv or 0.2 mg/kg ic) resulted in significant improvements in arterial pressure, myocardial contractility, and cardiac output. Treatment with saline or naloxone (0.2 mg/kg iv) were without beneficial effect. The hemodynamic responses to naloxone administered into the coronary circulation were dose dependent and stereospecific. These data support the hypothesis that naloxone exerts its salubrious effects in canine hemorrhagic shock by acting at cardiac opiate receptors. PMID- 4025563 TI - Dietary salt loading produces baroreflex impairment and mild hypertension in rats. AB - Mild hypertension with reduced chronotropic baroreflex sensitivity to phenylephrine occurred in Sprague-Dawley rats fed a high-salt diet for 5 wk. Progressive elevation of systolic and mean pressures, detected initially by indirect tail-cuff measurement, was later verified by direct recording of phasic pressures from indwelling aortic catheters in the same rats. Reflex bradycardia during pressor responses to phenylephrine was consistently less pronounced in salt-loaded than in control rats, whether tested while rats were awake or anesthetized. However, attendant decreases in renal nerve activity were not appreciably altered. Neither central nor carotid baroreceptor mechanisms were considered likely but aortic baroreceptors must have somehow been depressed because increases in afferent aortic nerve activity elicited during intravenous infusion of phenylephrine were invariably smaller in salt-loaded than in control rats. Whatever the underlying mechanisms may be, our results show that when hypertension develops during dietary salt loading, baroreflex chronotropic responses are selectively inhibited while attendant decreases in renal nerve activity are preserved. PMID- 4025564 TI - Crystalloid and perfluorochemical perfusates in an isolated working rabbit heart preparation. AB - Krebs-Henseleit buffer (KH) and a perfluorochemical (FC-43) were compared as perfusates in an isolated working rabbit heart preparation. Both perfusates were oxygenated in an identical manner using an infant bubble oxygenator. After 60 min of perfusion, no difference could be detected in the ratio of wet to dry heart weight between KH- and FC-43-perfused hearts (KH, 6.25 +/- 0.3; FC-43, 5.99 +/- 0.20). Left ventricular systolic pressure, maximal rate of left ventricular pressure rise, mean aortic systolic pressure, cardiac output, aortic flow, left ventricular power, and myocardial O2 consumption (MVO2) were significantly higher in FC-43-perfused hearts throughout the time of perfusion. However, there were no differences in resistance to cardiac output and heart rate. In KH- and FC-43 perfused hearts, MVO2 and left ventricular power were closely correlated (KH, r = 0.793; FC-43, r = 0.831). Significantly higher coronary flow of KH-perfused hearts could be attributed to the lower viscosity of KH (1.05 Pa . s) compared with FC-43 (1.91 Pa . s). Increased O2 extraction during KH perfusion could not compensate for low O2-carrying capacity of KH buffer (345 compared with 705 nmol O2 X ml-1 in FC-43 emulsion). A postischemic increase of coronary flow was observed only in FC-43-perfused hearts (28%). These results demonstrate a different response of perfused heart preparations to FC-43 and KH buffer. PMID- 4025565 TI - Mechanism for dynamic changes in stenotic severity. AB - The mechanism responsible for rapid changes in stenotic severity or resistance due to alterations in perfusion pressure and distal resistance is addressed by this study. An in vitro, eccentric arterial stenosis model was created using 15 canine carotid arteries cannulated with silicone plugs containing special pressure-transducing catheters designed to measure pressure directly, within the stenosis. The vessels were perfused at perfusion pressures of 150, 100, and 75 mmHg and at two levels of distal resistance while perfusion pressure, distal pressure, stenotic pressure, and flow were recorded. Orthogonal arteriograms were performed. Stenotic resistance was calculated as (perfusion pressure--distal pressure)/flow. All variables changed significantly (P less than 0.05) with decreases in perfusion pressure. Stenotic resistance always increased (P less than 0.02) as perfusion pressure or distal resistance decreased. These dynamic changes in stenotic resistance occurred at stenotic pressures well above the atmospheric, extraluminal pressure. Arteriographic data demonstrated decreasing stenotic luminal area with decreasing stenotic pressure. These results confirm the assertion that rapid changes in stenotic resistance are related to changes in stenotic luminal area and are not due to extrinsic forces. The principles of the Starling resistor are, therefore, not applicable to dynamic arterial stenoses. This information is immediately relevant to clinical situations in which complaint, severe stenosis results in ischemia. PMID- 4025566 TI - Intestinal hemodynamics in dogs with chronic one-kidney, one-wrapped hypertension. AB - In pentobarbital-anesthetized dogs with chronic one-kidney, one-wrapped perinephritic hypertension, the status of blood flow and resistance differs among vascular beds. There is normal blood flow with elevated resistance in the limb and elevated blood flow with normal resistance in the ileum. In the present study we investigated the mechanism of elevated flow and normal resistance in the ileum by measuring blood flow, pressure, O2 consumption, reactive hyperemia, pressure flow relationships, resistance at maximal vasodilation, and nonentrapment (shunting) of 9-microns microspheres in vascularly isolated, blood-perfused ilea of 11 24-h fasted dogs with chronic (greater than 4 wk duration) one-kidney perinephritic hypertension [1KH; PA = 163 +/- 8 (SD) mmHg] and 15 fasted normotensive one-kidney, sham-wrapped dogs (1KC; PA = 108 +/- 7 mmHg). In 1KH ileal blood flow was elevated by 35% (P less than 0.001), but ileal vascular resistance was unchanged. Pressure-flow relationships were similar in hypertensive and normotensive ilea, with little evidence for significant autoregulation in either. We also noted no significant differences in ileal O2 consumption, reactive hyperemia, or resistance at maximal vasodilation. However, we found nonentrapment of microspheres to be a positive function of perfusion pressure (P less than 0.02) and to be increased by 40% during ileal perfusion at levels of perfusion pressure within the hypertensive range (150-200 mmHg). Thus the increased ileal blood flow in 1KH may reflect the effects of a poorly autoregulating tissue, as well as "shunt" flow through pressure-activated channels.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4025568 TI - Evidence and quantitation of left ventricular systolic resistance. AB - Instantaneous left ventricular pressure is a function of both volume (elastic behavior) and flow (resistive behavior). However, a quantitative description of ventricular resistance and its effects on ventricular performance remains to be elucidated. Accordingly, ventricular resistive behavior was studied in six isolated canine hearts. Our experimental findings indicate 1) for a specified time (ts), volume (Vs), and contractile state (CS), the ventricular pressure-flow relation was linear (r = 0.96-0.99) within the range of flows examined (0-250 ml/s); 2) ventricular resistance increased with increments in ts, Vs, and CS, whereas the zero-pressure flow intercept was invariant; 3) resistance could be uniquely quantified as a linear function of isovolumetric pressure. In six experiments, the slope of this relationship ranged from 1.1 to 2.1 X 10(-3) s/ml while the intercept did not differ from zero; and 4) end-systolic elastance, estimated from end-systolic pressure-volume data, was in substantial error under the conditions of finite (greater than 35 ml/s) end-systolic flows. Finally, the results from a computer simulation of the coupled ventricular-arterial system indicated that ventricular resistance primarily affects the pulsatile nature of aortic flow. The unique isovolumetric pressure-resistance relation suggests that the rate-limiting properties of the contractile process may be causally related to the observed ventricular resistive behavior. PMID- 4025567 TI - Sodium-dependent hypertension produced by chronic central angiotensin II infusion. AB - Experiments were performed to characterize the hypertension produced by chronic intracerebroventricular (ICV) infusion of angiotensin II (ANG II) in conscious rats. Infusion of ANG II into a lateral cerebral ventricle for 5 days (1 or 6 micrograms/h) produced dose-dependent increases in mean arterial pressure associated with increased water intake. No consistent changes in heart rate, urinary electrolyte excretion, or water balance were observed. Similarly, no alterations in plasma sodium and potassium concentration, plasma osmolality, or plasma ANG II levels were seen during ICV ANG II infusion. Controlling fluid intake at 40 ml/day did not alter the development of hypertension in this model. Hypertension was found to be sodium dependent, with high sodium intake augmenting the increase in arterial pressure in response to chronic ICV ANG II. Although plasma aldosterone concentrations were increased in some situations during ICV ANG II infusion, adrenalectomy failed to alter the course of hypertension. This study demonstrates that chronic selective stimulation of brain ANG II receptors by means of continuous ICV infusion of ANG II produces sodium-sensitive increases in arterial pressure associated with, but not dependent on, increased fluid intake. This form of hypertension cannot be attributed to sodium and water retention, elevations in plasma aldosterone, or leak of significant amounts of ANG II from cerebrospinal fluid into the peripheral circulation. PMID- 4025569 TI - Evidence that capillary perfusion heterogeneity is not controlled in striated muscle. AB - We tested the hypothesis that the heterogeneity of capillary blood flow distribution in striated muscle is inversely proportional to tissue blood flow by examining the patterns of red blood cell flow in the capillaries of hamster tibialis anterior muscles. Capillary red blood cell velocities and capillary red blood cell fluxes were measured as indexes of blood flow and red blood cell distribution in vasoconstricted and vasodilated vascular beds of resting and working striated muscle. Standard statistical parameters describing dispersion of data (standard deviation and coefficient of variation) in addition to measured and normalized histograms were compared across treatments. With vasodilation the standard deviations of both variables increased linearly with the means, and measured distributions became broader. The coefficients of variation and normalized distributions of both variables did not differ across treatments. These observations do not support the idea that the heterogeneity of capillary perfusion is controlled. Rather they suggest that fractional flow dispersion among capillaries is constant and independent of muscle blood flow and/or O2 demand. PMID- 4025570 TI - Cerebrovascular hypoxic and autoregulatory responses during reduced brain metabolism. AB - The effect of reducing cerebral oxygen consumption (CMRO2) on the cerebral blood flow (CBF) responses to isocapnic hypoxic hypoxia and hypotension was examined in sheep. Newborn and adult animals were studied because of their different base line CMRO2. Microsphere-measured CBF responses during pentobarbital coma (i.e., electroencephalographic silence) were compared with responses in conscious or lightly sedated animals. Induction of barbiturate coma reduced both CMRO2 and CBF by 50% from the awake value and by 25% from the value obtained in animals sedated with pentobarbital. The CBF response to 30 and 50% reductions in arterial O2 content (CaO2) was attenuated during coma, but only in proportion to the decrease in CMRO2. Whether CMRO2 was normal or reduced, the normoxic cerebral O2 delivery (CaO2 X CBF) was maintained during hypoxia in both newborns and adults. The relative autoregulatory index (fractional change in CBF divided by fractional change in perfusion pressure) was determined during graded hemorrhage. The index was not significantly different from zero (which represents perfect autoregulation) in awake, lightly sedated, or comatose animals. The data demonstrate that both base-line CBF and responses to hypoxia are closely tied to CMRO2 and that 50% reduction of CMRO2 does not impair cerebrovascular autoregulation. PMID- 4025571 TI - Hemodynamic and regional circulatory alterations in dog during anaphylactic challenge. AB - Microspheres were employed to measure the cardiac output (CO), percent distribution of CO (%CO), and blood flow (BF) to various tissues in the dog during anaphylactic shock. Five minutes after challenge there was a 66 and 83% drop from control for mean arterial pressure and CO, respectively. Arterial glucose and lactic acid rose 62 and 537%, respectively. Furthermore, there was a narrowing of the systemic arteriovenous difference for PO2 and a widening of the venoarterial difference for PCO2. Pressure compensation toward control values began 5 min postchallenge and continued through 180 min. Circulatory perturbations during severe hypotension (less than mmHg) included depressed %CO and BF to the pancreas and spleen and elevated %CO to the brain and adrenals. Cerebral and adrenal BF remained unchanged at this period. BF to the kidneys, liver (hepatic artery), and gastrointestinal tract dropped markedly as a function of increased peripheral resistance and decreased CO. As cardiac performance improved, blood flow to the pancreas, spleen, liver, diaphragm, and gastrointestinal tissues returned toward control but was elevated to the adrenals and decreased to the brain. PMID- 4025572 TI - Effects of intracardiac bradykinin on T2-T5 medial spinothalamic cells. AB - Effects of injecting bradykinin (2 micrograms/kg) into the left atrium on spinothalamic tract neurons projecting to medial thalamus (M-STT cells), to the ventral posterior lateral nucleus of the thalamus (L-STT cells), or to both (LM STT cells) were examined in 18 monkeys (Macaca fascicularis) anesthetized with alpha-chloralose. Bradykinin increased cell activity in 11/16 M-STT cells, 10/15 L-STT cells, and 4/7 LM-STT cells. One M-STT cell was inhibited. Peak responses to bradykinin of the three cell groups were not different. LM-STT cells began to respond and reached peak responses slightly earlier than the other two groups. Six M-STT, four L-STT, and two LM-STT cells became entrained to the cardiac cycle during their responses to bradykinin. Responses to bradykinin were not dependent on the type of somatic input or cell location. Responding cells most often received A delta- and C-fiber sympathetic input, but some responding cells had only A delta-input. These results demonstrate that in addition to L-STT cells STT cells projecting to the medial thalamus respond to a potentially noxious cardiac stimulus. These cells may participate in the motivational-affective component of cardiac pain. PMID- 4025573 TI - Oscillatory temperature response to constant power applied to canine muscle. AB - A previously unreported oscillatory temperature response has been observed in canine thigh muscle subjected to an abrupt application of a constant specific energy absorption rate (SAR). The power was applied to anesthetized dogs (stage 3 plane of anesthesia) using 2,450-MHz microwaves. Five types of responses have been identified that have occurrences depending on the maximal temperature produced by the applied power. In particular, for SAR values resulting in sufficiently high initial temperatures, self-sustaining temperature oscillations lasting over 4 h have been observed with amplitudes up to 7 degrees C. The temperature oscillations are believed to be caused by oscillations in the local blood perfusion rate. PMID- 4025574 TI - Osmotic factors in restitution from thermal dehydration in rats. AB - The degree of voluntary dehydration after thermal dehydration was assessed while supplying drinking water of varying NaCl concentrations. Adult male albino rats were exposed to a hot-dry environment (dry bulb temp 36 degrees C; relative humidity 20%) for 6-8 h, and dehydration of 7% body wt was induced. After dehydration the rats were divided into three groups, and distilled water and 0.45 or 0.9% NaCl solution was given ad libitum. The amount of fluid intake reached an equilibrium in 6-12 h; the 0.45 and 0.9% NaCl groups regained almost all lost water, whereas the distilled water group regained only half. During rehydration the 0.45 and 0.9% NaCl groups gained Na by approximately 430-650 mueq and lost K by 90-130 mueq, whereas the distilled water group lost Na slightly and K by 80 mueq/100 g body wt. As for the electrolyte balance during thermal dehydration, rats excreted Na and K into urine and saliva. Na loss was 200 mueq/100 g, almost all of which was derived from the interstitial space of skin and skeletal muscle, and K loss was 230 mueq/100 g, almost all of which was derived from intracellular space of skeletal muscle. Total cation loss (Na, K) during thermal dehydration, including K excretion during rehydration, was 510-560 mueq/100 g, which was almost identical to the Na gained by rats given 0.45 or 0.9% NaCl solution. These results suggest that voluntary dehydration is caused by the dilutional inhibition of drinking due to loss of electrolytes during thermal dehydration. PMID- 4025575 TI - Hemodynamics during pregnancy and sex steroid administration in guinea pigs. AB - We investigated the time course and possible mechanisms by which the maternal cardiovascular system adapts to the demands of pregnancy. Control, 20-, 40-, and 60-day gestation guinea pigs (total 68 days) and nonpregnant virgin female guinea pigs chronically dosed with cholesterol (control), estrogen (17beta-estradiol), progesterone, and estrogen plus progesterone were studied. In vivo heart rates, pressures, cardiac outputs, blood volumes, and in vitro left ventricular pressure volume relations were measured. There was no difference in heart rate, mean arterial, right atrial, or left ventricular end-diastolic pressures, or left ventricular weights between the various pregnant animals or hormone-dosed animals and their respective controls. By 20 days gestation blood volume (24%, P less than 0.005), cardiac output (22%, P less than 0.005), and stroke volume (22%, P less than 0.05) were increased, whereas uterine blood flow was unchanged. Chronic estrogen administration resulted in similar increases in cardiac output (24%, P less than 0.05), stroke volume (31%, P less than 0.05), and blood volume (13%, P less than 0.05). In vitro left ventricular pressure-volume relations were shifted to the right in all pregnant and hormone-dosed groups. Increases in left ventricular size and output occur before changes in uterine blood flow in guinea pig pregnancy, and these adaptations can be elicited by chronic sex steroid administration. PMID- 4025576 TI - Menstrual cycle phase and time of day alter reference signal controlling arm blood flow and sweating. AB - The changes occurring in the esophageal temperature (Tes) thresholds for initiation of heat loss responses as affected by the circadian period and menstrual cycle were studied. Four women exercised at 60% peak Vo2 in 35 degrees C (ambient water vapor pressure 1.73 kPa) for 30 min at 0400 and 1600 during the follicular (F) and luteal (L) phase. Tes, arm sweating rate (msw), and forearm blood flow (FBF) were measured frequently. At rest, Tes averaged 0.3 degrees C higher during L than F at both 0400 and 1600 and approximately 0.4 degrees C higher at 1600 than at 0400 during both phases. During exercise transients, the slopes of the FBF:Tes and the msw:Tes relationships were not different among treatments. The thresholds for initiation of sweating and cutaneous vasodilation were higher at 1600 than 0400 during both phases. Thresholds during F at 0400 averaged 36.44 degrees C for msw and 36.80 degrees C for vasodilation. The thresholds during L at 1600 averaged 37.46 and 37.53 degrees C for sweating and vasodilation, respectively. Our data indicate that the thermoregulatory effector activity during exercise is a function of numerous inputs, and one of these may be hormonal or hormonal-like in action. Controlling time of day and menstrual cycle phase are as important as controlling for aerobic power, age, and fitness in studying female thermoregulatory responses during exercise. PMID- 4025577 TI - Mathematical model of fetal circulation and oxygen delivery. AB - To better understand the fetal circulation and its regulation we constructed a dynamic model of fetal circulation as a transport system. The fetal vascular system is divided into 16 compartments which incorporate the peculiarities of the fetal circulation that produce a difference in oxygen concentration in blood supplying the upper and lower body. Recently published data is used to provide a firm experimental base for the model. The model is used to examine how the results on parts of the fetal cardiovascular system and fetal oxygen consumption are compatible and form a coherent description. We also studied the effects of disturbances from the normal steady state produced by changes in patterns of and resistances to blood flow. A maternal placental blood flow of less than 200 ml X min-1 X kg fetal wt-1 produces a steady-state value of oxygen tension in the fetal ascending aorta of less than 17 mmHg, which is incompatible with normal oxygen delivery. A minimal value of umbilical flow providing an adequate oxygen supply to the fetal body is 87 ml X min-1 X kg fetal wt-1. Due to the geometry of the fetal circulation, the highest normal oxygen tension in the fetal ascending aorta is approximately 25 mmHg, only 8 mmHg above the lowest normal tension of 17 mmHg. Dynamic studies using the model demonstrate differences in response of fetal arterial oxygen tension to temporal cord occlusion and temporal decrease in maternal placental flow. PMID- 4025578 TI - Calcium regulation in blowflies: absence of a role for midgut. AB - Adult blowflies (Calliphora vicina) survive many days without increased mortality if fed 12.5 mM CaCl2 solution in place of water. Initially the calcium content of these flies rapidly increases to more than double the original content but then remains stable for many days afterward. Calcium absorption continues at a similar rate throughout this time. Midguts isolated from flies fed either 12.5 mM CaCl2 solution or distilled water have the same capacity to absorb calcium. Dopamine, octopamine, proctolin, and 5-hydroxytryptamine, at pharmacological doses, do not affect calcium absorption by the isolated midgut. Malpighian tubules are the site of most rapid calcium turnover when flies are fed excess calcium. It is concluded that excretion and not absorption is the major site of hemolymph calcium regulation in C. vicina. This contrasts to the situation in mammals where transcellular calcium absorption by the duodenum is precisely controlled. It is suggested that to avoid high luminal calcium concentrations, fast calcium absorption from the blowfly midgut is adapted to remove calcium from the lumen rather than to regulate hemolymph calcium concentration. PMID- 4025579 TI - Subfornical organ and supraoptic nucleus connections with septal neurons in rats. AB - Extracellular single unit recordings obtained in pentobarbital-anesthetized male Sprague Dawley rats were utilized to examine the electrophysiology of connections of medial septum-diagonal band of Broca (MS-DBB) neurons with the subfornical organ (SFO), hippocampal commissure (HC), and supraoptic nucleus (SON). Of the 119/216 cells tested that demonstrated antidromic activation from SON, many (60%) were orthodromically excited by SFO stimulation, whereas most (68%) were unresponsive to stimulation in the adjacent HC. Separate populations of MS-DBB neurons that displayed antidromic activation from the SFO (11/140 cells tested) or HC (24/78 tested) were orthodromically excited by SON stimulation. Three cells were activated antidromically from both the SFO and SON. These observations reveal some possible interconnections between these three brain regions and point to the existence of an indirect pathway whereby the SFO can influence SON neurons through an influence on MS-DBB neurons. PMID- 4025580 TI - Renal function in sea snakes. I. Glomerular filtration rate and water handling. AB - Renal clearance studies were performed on anesthetized sea snakes (Aipysurus laevis) under various salt and volume loads. The median values for the control glomerular filtration rate (GFR) and urine flow rate (V) were 0.78 and 0.11 ml X kg-1 X h-1, respectively. Acute salt loading with 1 mol/l NaCl significantly increased V to 0.68 ml X kg-1 X h-1, whereas acute water loading significantly decreased GFR to 0.17 ml X kg-1 X h-1. Acute loading with either isosmotic NaCl or seawater did not significantly alter either V or GFR. Chronic loading with water or seawater by intraperitoneal injection significantly increased both GFR and V. No consistent relationship between plasma osmolality and GFR was observed. Instead a threshold-type relationship existed between GFR and plasma K concentration. Within each treatment group, high plasma K concentrations were correlated with low GFRs. There was an abrupt increase in GFR at low plasma K concentrations, the inflection point ranging from 2.5 to 4 mmol/l K depending on the experimental treatment. A curvilinear relationship existed between V and GFR; as GFR increased, V approached a maximal limiting value. At low GFRs (less than 0.2 ml X kg-1 X h-1), V often exceeded GFR, indicating net fluid secretion that was correlated with net Na movement. In addition, there was an inverse relationship between urine-to-plasma osmolality ratio and V. At low values of V, urine osmolalities modestly exceeded those of the plasma. Overall, renal function of A. laevis appears to be adapted to conserve water. PMID- 4025581 TI - Renal function in sea snakes. II. Sodium, potassium, and magnesium excretion. AB - Renal clearance studies performed on the sea snake Aipysurus laevis demonstrated net tubular reabsorption of Na and both net tubular secretion and reabsorption of Mg and K. Fractional excretion of Na (FENa) was 0.05 under control conditions and increased markedly with hyperosmotic salt loading. Within each group, however, higher glomerular filtration rates were accompanied by disproportionately greater Na reabsorption. FEMg was 0.66 under control conditions and increased with Mg loading. The rate of Mg secretion was positively correlated with the urine flow rate. However, Mg loading caused a flow-independent increase in Mg secretion that was correlated with increasing plasma Mg concentration. FEK was 0.86 under control conditions and increased with K loading as a result of enhanced K secretion by the renal tubules. Like renal Mg secretion, renal K secretion showed a flow-dependent component as well as a flow-independent component related to plasma K concentration. PMID- 4025582 TI - Energy expenditure is reduced in preobese 2-day Zucker fa/fa rats. AB - The rate of oxygen consumption was measured in 2-day Zucker preobese (fa/fa), homozygous (Fa/Fa) lean, and lean rats of unknown genotype (Fa/?) over the ambient temperature range of 26-35 degrees C. Significant differences in body mass were found among the three groups at this early age, the preobese pups having the greatest body mass. To account for body mass differences, the oxygen consumption data were expressed in terms of metabolic body size (ml O2 consumed X g body mass-2/3 X h-1). This mass-independent rate of oxygen consumption was significantly lower in the preobese pups than in the homozygous lean (Fa/Fa) pups at both thermoneutral (33-34 degrees C) and cold (26-27 degrees C) ambient temperatures at which, respectively, minimal and maximal rates of oxygen consumption were observed. This reduction in energy expenditure occurs before the establishment of hyperphagia or decreased levels of activity in the preobese pups. These data support the view that attenuated energy expenditure is a significant contributor to the early development of obesity in the Zucker fatty rat and point to the possibility of defective brown adipose tissue-mediated thermogenesis in the preobese pup. PMID- 4025583 TI - Influence of central chemoreceptor afferent inputs on respiratory muscle activity. AB - Respiratory activity can be substantially affected by perturbations confined to the superficial areas of the ventrolateral surface of the medulla, the putative site of central chemoreceptors. In this study we compared the effect of thermal and pharmacological interventions that are known to alter respiration on the electrical activity of the rib cage muscles, diaphragm, and abdominal muscles. With cooling of the intermediate areas to 20 degrees C, tidal volume decreased 50%. The electrical activity of the diaphragm decreased less than the other muscles (diaphragm less than inspiratory intercostal less than expiratory intercostal). Abdominal muscle activity was depressed as much as expiratory intercostal activity but reappeared with further cooling to 10 degrees C if cooling was prolonged and the vagi were intact. gamma-Aminobutyric acid (GABA) and its agonist muscimol, like cooling, reduced expiratory and inspiratory intercostal activity more than diaphragm activity. Nicotine, a respiratory stimulant, applied to the intermediate areas increased inspiratory intercostal activity more than the diaphragm. The results suggest that under the conditions of the experiments the rib cage musculature, and probably the abdominal muscles as well, are more responsive than the diaphragm to depression or excitation of chemosensitive elements in the superficial regions of the medulla. PMID- 4025584 TI - Psychotic syndromes in epilepsy. AB - Claims have been made that epilepsy is associated with both brief psychotic episodes and persistent psychotic states. The existence of brief, nonconfusional psychotic episodes in epilepsy has received some formal support; these may be a function of temporal lobe subictal activity. Persistent psychosis is found in about 7% of patients with epilepsy; independent evidence indicates this to be a significant association. Temporal lobe seizure activity, again probably acting subictally, may be involved in the pathogenesis of these states, perhaps in interaction with other factors. Occurrence of psychotic syndromes in epilepsy may be relevant to kindling, atypical psychoses unrelated to epilepsy, and the psychotropic effect of carbamazepine. PMID- 4025585 TI - Extended sleep (hypersomnia) in young depressed patients. AB - To test the hypothesis that young depressed patients have prolonged rather than shortened sleep, 14 depressed patients aged 17-25 and age-matched normal control subjects were allowed to sleep as long as they wanted. All subjects increased their sleep over baseline values, but the extended sleep period of the depressed patients was almost twice as long as that of the control subjects. The distribution of sleep stages in the extended period did not differ. The depressed patients had changes in the length of REM periods similar to those of older subjects. The findings suggest an interaction between age, sleep, and depression. PMID- 4025586 TI - Empathy and outcome in brief focal dynamic therapy. AB - In an attempt to test the hypothesis that therapist empathy is an important variable in successful dynamic therapy, the authors collected outcome measures and empathy ratings in the brief focal dynamic therapy of 59 patients. There was no significant agreement among patients, therapists, and clinical supervisors when they used the same scale to rate therapist empathy for the same sessions. Only the patients' ratings correlated significantly with some of the outcome measures, and they added modest but statistically significant predictive variance on multiple regression analysis. The authors discuss the implications of these findings for the traditional mode of supervision of dynamic therapy. PMID- 4025587 TI - Therapist actions that address initially poor therapeutic alliances in psychotherapy. AB - The authors studied six patients treated in time-limited dynamic psychotherapy who had initially poor therapeutic alliance scores; three patients went on to have improved alliances and good outcomes, and three had unimproved alliances and poor outcomes. The therapist actions that most strongly differentiated the two groups and occurred more frequently in the cases with improved alliances and good outcomes were 1) addressing the patient's defenses, 2) addressing the patient's guilt and expectation of punishment, 3) addressing the patient's problematic feelings in relation to the therapist, and 4) linking the problematic feelings in relation to the therapist with the patient's defenses. PMID- 4025588 TI - Familial transmission of schizotypal and borderline personality disorders. AB - The authors determined the risk for psychiatric disorders in the first-degree relatives of 36 probands with schizotypal personality disorder (13 definite, 23 probable), 17 probands with borderline personality disorder (two definite, 15 probable), and 90 normal control probands. The relatives of probands with schizotypal personality disorder without a concurrent diagnosis of borderline personality disorder had a significantly greater risk for schizotypal personality disorder than the relatives of normal control probands, borderline probands, or schizotypal probands with coexisting borderline personality disorder. The relatives of borderline probands had a significantly greater risk for definite and probable borderline personality disorder than the relatives of normal control probands. PMID- 4025589 TI - When doctors listen: counseling patterns of nonpsychiatrist physicians. AB - Recent work has shown that nonpsychiatrist physicians are surprisingly active in the mental health arena. Using the two most recent National Ambulatory Medical Care Surveys (1980-1981), the authors analyzed the provision of counseling services by general medical physicians in more detail. Office visits involving counseling were a third again as long as the average office visit (20 minutes versus 15) and involved notably more diagnostic and therapeutic services. Although patients who received counseling services from nonpsychiatrist physicians were generally not mentally ill, about one in eight did have a psychiatric diagnosis and might have been better served in the mental health sector. PMID- 4025590 TI - Value of difficult temperament among 7-year-olds in the general population for predicting psychiatric diagnosis at age 12. AB - The authors assessed the predictive value of "difficult" temperament, as defined in the New York Longitudinal Study, in 12-year-old children from the general population of Quebec City whose temperaments had been determined to be difficult or easy at age 7. The difficult and easy temperament groups were balanced for age, sex, and socioeconomic status. The authors used many convergent measuring devices and were blind to the temperament scores of the children at age 7. Temperamentally difficult children had more clinical disorders at age 12 that qualified for a DSM-III diagnosis. An association with family dysfunction in terms of behavior control seemed to increase this risk: there was a lower rate of clinical disorders among children in superior functioning families than among those in dysfunctional families. PMID- 4025591 TI - Specificity of lactate infusions in social phobia versus panic disorders. AB - Lactate infusions produced panic attacks in one of 15 patients with social phobia, four of nine with agoraphobia, and 10 of 20 with panic disorder in a blind study. The proportion of patients with social phobia who panicked in response to lactate was significantly lower than that of patients with agoraphobia or panic disorder. These findings lend validity to the DSM-III classification of anxiety states. They also suggest that the pathophysiology of social phobia differs from that of disorders characterized by spontaneous panic attacks. PMID- 4025592 TI - Hair analysis for detection of phencyclidine in newly admitted psychiatric patients. AB - The authors implemented a new procedure for analyzing phencyclidine (PCP) content in hair. They compare the results of analyses of hair with results of analyses of blood and urine in 47 patients newly hospitalized with acute psychiatric illness. Hair analysis identified 11 patients who had used PCP, and blood and urine analyses did not identify any among the sample population. In three patients, the results of hair analysis aided in establishing a diagnosis of PCP intoxication. The authors discuss interpretations of their findings and psychiatric applications of this new technique. PMID- 4025593 TI - Dissociation and psychotic symptoms. AB - The literature on hysterical or brief reactive psychosis reflects great diversity both in clinical description and theoretical formulation. The authors describe the case of a 17-year-old girl who presented with a diagnosis of bipolar affective disorder, rapid cycling type, but who, in fact, was experiencing dissociative episodes manifested as psychotic states. The patient's successful treatment with hypnosis is described, along with the clinical and theoretical implications of the case. PMID- 4025594 TI - One-year follow-up study of posttraumatic stress disorder among survivors of Cambodian concentration camps. AB - One year after receiving a diagnosis of posttraumatic stress disorder, five of 12 Cambodian concentration camp survivors who entered a treatment program no longer met the diagnostic criteria for the disorder, and symptoms in three others had improved. The intrusive symptoms of nightmares, sleep disorders, and startle reactions showed the most consistent improvement. Avoidance behavior, shame, and caring for others improved the least. The authors advocate use of tricyclic antidepressant medication and a consistent, supportive long-term psychotherapeutic commitment in treating this severely traumatized group. PMID- 4025595 TI - Assaultive behavior among psychiatric outpatients. AB - Of 2,916 patients evaluated by psychiatric residents in the outpatient clinics of two large private psychiatric hospitals, 3% had manifested recent assaultive behavior toward other persons. In over half the cases the target of assault was a family member other than a child. Patients more likely to be assaultive were young and male and had a diagnosis of childhood or adolescent disorder or personality disorder. The authors compare these results with those from studies of assault among inpatients and recommend that physicians in outpatient as well as inpatient settings be familiar with the management of assaultive patients. PMID- 4025596 TI - Noninstitutional treatment for sex offenders in Florida. AB - The authors describe the availability and characteristics of noninstitutional treatment for sex offenders found in a survey of 63 community mental health providers in Florida. The results cover offense categories, referral sources, numbers in treatment, annual case load, and program characteristics. More sex offenders were being treated in the community than in state-operated residential programs, and 21% of the patients currently receiving community treatment were self-referred. The authors recommend that researchers and policy makers direct more attention to community treatment of sex offenders, its efficacy, and training for those delivering the treatment. PMID- 4025597 TI - A typology of near-death experiences. AB - Cluster analysis of 89 near-death experiences yielded three discrete types of such experiences: transcendental, affective, and cognitive. Demographic variables did not differentiate individuals having these different types of experiences, but cognitive near-death experiences were less frequent following anticipated near-death events. PMID- 4025598 TI - Midsagittal sections of the cerebellar vermis and fourth ventricle obtained with magnetic resonance imaging of schizophrenic patients. AB - Measurements of the cerebellar vermis and height of the fourth ventricle made from midsagittal brain images obtained with magnetic resonance imaging did not show any differences between patients with schizophrenia and matched normal control subjects. PMID- 4025600 TI - ECT and multichannel EEG recording. PMID- 4025599 TI - Plasma amine oxidase and clinical features of schizophrenia. AB - Among 76 chronic schizophrenic patients, plasma amine oxidase activity was unrelated to paranoid/nonparanoid subtype, narrow/broad diagnostic criteria, prognosis, or age at onset. These clinical indices do not identify biological subtypes of schizophrenia with deviant plasma amine oxidase activity. PMID- 4025601 TI - The DST in depressed alcoholic patients. PMID- 4025602 TI - Adolescent suicides modeled after television movie. PMID- 4025604 TI - Early memories and dream formation. PMID- 4025603 TI - Lymphocyte sensitivity to glucocorticoids. PMID- 4025605 TI - The DST and organic affective disorder. PMID- 4025606 TI - On fraud among psychiatrists. PMID- 4025607 TI - Blinking frequency and dopamine availability. PMID- 4025608 TI - Genetics of schizophrenia and the positive-negative dimension. PMID- 4025609 TI - Platelet MAO in functional psychoses with evidence of brain atrophy. PMID- 4025610 TI - Homelessness not a mental health problem. PMID- 4025611 TI - Violence and epilepsy in South Africa. PMID- 4025612 TI - Is psychosis endemic in western Ireland? PMID- 4025613 TI - Metamorphopsias caused by pontine and peduncular lesions. PMID- 4025614 TI - The DST in newly hospitalized patients. PMID- 4025615 TI - Presidential address: Our patients' future in a changing world: the imperative for psychiatric involvement in public policy. PMID- 4025616 TI - Response to presidential address: unity amidst diversity: future challenges. PMID- 4025617 TI - A profile of clients referred for psychiatric evaluation for Social Security Disability Income and Supplemental Security Income: implications for psychiatry. AB - A study of the psychiatric evaluations of 248 consecutive clients whose cases were in the process of adjudication for approval or renewal of Supplemental Security Income and/or Social Security Disability Income in 1982 and 1983 showed an overrepresentation of individuals with chronic moderate to severe psychiatric impairment. The author suggests that the criteria and guidelines for eligibility for these two programs are too stringent for individuals with psychiatric impairment and that some of these individuals are unable to provide information necessary to build a proper case for disability because of their psychopathology. The implications for psychiatrists, other mental health professionals, and social policy planners are discussed. PMID- 4025618 TI - Ethics in the practice of psychiatry: update on the results of enforcement of the code. AB - From 1950 to 1973, 82 charges of unethical conduct were made against APA members; of the 12 (15%) members who were found unethical, six were expelled. From 1972 to 1983, 382 members were charged; 86 (23%) were found unethical and 27 of them were expelled. The charges most often involved patient exploitation and illegal conduct. The proportion of the membership charged in each APA area varied by as much as 3:1; some district branches had many charges (69 was the most), and many had none. With all the limitations, the system of enforcement is valuable, but there is much room for improvement. PMID- 4025620 TI - Toward unity: the joint statement of the American Medical Association and the American Psychiatric Association regarding the insanity defense. PMID- 4025619 TI - Should physician training centers offer formal psychiatric assistance to house officers? A report on the major findings of a prototype program. AB - The literature suggests that the emotional needs of interns, residents, and fellows have received inadequate attention. Comprehensive psychiatric services are provided by a model program at UCLA. During the 1981-1983 academic years, 89 house officers were seen. Between 16% and 19% of certain groups sought help each year; depression was the most frequent diagnosis (63%, N = 56), followed by anxiety disorders (24%, N = 21). Over two-thirds of the evaluated residents entered free or low-fee treatment, and these therapies were generally considered quite beneficial. This report reemphasizes the desirability of providing carefully structured, confidential psychiatric assistance to house staff and documents medical trainees' acceptance and use of such programs. PMID- 4025621 TI - Rationale for reporting standard deviations rather than standard errors of the mean. PMID- 4025623 TI - Correlation between serum and salivary cortisol levels in depressed and nondepressed children and adolescents. AB - Serum and saliva cortisol levels were determined in 34 depressed and nondepressed children and adolescents. The serum and salivary measures were highly correlated. The measurement of salivary cortisol may be a useful noninvasive technique in the study of cortisol secretion patterns in young subjects. PMID- 4025622 TI - Psychological autopsy of completed suicide in children and adolescents. AB - A psychological autopsy of 20 children and adolescents aged 12-19 years who had committed suicide and a matched-pair control group revealed that 85% of the victims and 18% of the control subjects had expressed suicidal ideation. A statistically significant number of the victims had a history of suicide threats (55%), suicide attempts (40%), drug or alcohol abuse (70%), antisocial behavior (70%), or inhibited personality (65%). Suicidal behavior of parents, relatives, or friends and a parental history of emotional problems and absence or abusiveness were also significant factors for the victims. PMID- 4025624 TI - Mania in two sisters with similar cerebellar disturbance. AB - The authors describe two sisters who presented with a clinical picture consistent with mania. On further investigation, both had marked vermian and cerebellar cortical atrophy on CAT scans. Their mother also had a history suggestive of cerebellar disease. To the authors' knowledge, this is the first report of familial cerebellar disease with a clinical presentation of mania. PMID- 4025625 TI - Posttraumatic stress disorder: a thirty-year delay in a World War II veteran. AB - Some clinicians doubt the validity of a diagnosis of delayed posttraumatic stress disorder for Vietnam veterans. Precombat psychopathology, drug abuse, factitious symptoms, and malingering in pursuit of disability compensation are cited as alternative explanations for the syndrome. The authors discuss the case of a much decorated World War II veteran whose symptoms of posttraumatic stress disorder first occurred more than 30 years after combat. They consider the alternative explanations for his symptoms to be inadequate. PMID- 4025626 TI - Miranda comes to the hospital: the right to remain silent in civil commitment. AB - One procedural protection that has not generally made the transition from the criminal justice system to involuntary civil commitment is the Fifth Amendment protection against self-incrimination. The authors present the results of a study of the implementation of the right to remain silent, which demonstrate that warning patients that anything they say may be used against them in the commitment hearing has little impact on their willingness to talk to staff or to cooperate with treatment. The authors discuss the possible reasons for their findings. PMID- 4025628 TI - A study of 10 men charged with patricide. AB - The authors reviewed the records of 10 men charged with patricide, including one charged with double parricide, all of whom had been examined at the Forensic Psychiatry Service of Bellevue Hospital from 1970 to 1983. Prior psychoses were documented in all subjects; nine were referred to as delusional. Four perceived their fathers as having posed threats of physical or psychological annihilation to them, and five saw paternal threats to their manhood. The 10th man allegedly killed his father during a drunken brawl. PMID- 4025627 TI - Family expressed emotion and relapse in schizophrenia in 24 urban American patients. AB - The authors examined the correlation between family expressed emotion and relapse in 24 schizophrenic patients in a predominantly inner-city American setting. They found a significant correlation between relapse and high expressed emotion in family members; the level of family expressed emotion was somewhat higher than that reported in previous studies. The findings suggest that the impact of expressed emotion may vary in different sociocultural populations. PMID- 4025629 TI - Patterns of psychiatric consultation in a Chinese general hospital. AB - The authors conducted a study of psychiatric consultation in a Chinese general hospital. Seventy-five inpatients (0.74% of the patients in the hospital) were referred by different services over a 1-year period. Internal medicine referred the most patients, and organic brain syndromes were the most common diagnoses. Depression was not a frequent diagnosis, but neurasthenia was a fairly common one. None of the referred patients had a diagnosis of alcoholism, drug abuse, or personality disorder. The authors compare these data with those of Western studies and discuss the possible factors influencing psychiatric consultation in China. PMID- 4025630 TI - Serial ECG measurements at controlled plasma levels of nortriptyline in depressed children. AB - The authors investigated ECG measurements in 21 children with major depressive disorder treated with nortriptyline at plasma levels of 50-100 ng/ml. P-R and QRS intervals and heart rate measured at baseline and once a week during treatment remained within guidelines. PMID- 4025631 TI - The limited usefulness of nasopharyngeal EEG recording in psychiatric patients. AB - The authors retrospectively studied 150 psychiatric inpatients, 96 of whom had had nasopharyngeal EEGs and 54 of whom had had regular EEGs. The nasopharyngeal recordings did not reveal significantly more epileptiform abnormalities than did the regular EEG in patients with suspected seizures. PMID- 4025632 TI - Depression after treatment with thiazide diuretics for hypertension. AB - The authors reports eight cases of depression induced by thiazide diuretics prescribed for hypertension and discusses possible mechanisms behind this action. The side effects of thiazide diuretics may be overlooked when they are used with other hypertensives known to cause depression. PMID- 4025633 TI - Subjective memory complaints in geriatric depression. AB - Improvement in depressive symptoms was significantly related to a decrease in subjective memory complaints in 29 elderly depressed outpatients. Patients with substantial improvement in their depression showed similar reductions in memory complaints regardless of whether they received tricyclic antidepressants or group psychotherapy. PMID- 4025635 TI - Dysmorphophobia and monosymptomatic hypochondriasis. PMID- 4025634 TI - Metoprolol for intermittent explosive disorder. AB - Metoprolol, a selective beta 1-adrenoreceptor blocker, was administered to two patients with intermittent explosive disorder who had not done well with previous medications, including propranolol and carbamazepine. Both patients improved dramatically, suggesting clinical and theoretical relevance. PMID- 4025636 TI - Psychiatric epidemiology and clinical psychiatry. PMID- 4025637 TI - Plasma dexamethasone and elevated DST cortisol level. PMID- 4025638 TI - "Atypical posttraumatic stress disorder" is misleading. PMID- 4025639 TI - Light-induced hypomania. PMID- 4025640 TI - Right to refuse treatment and delayed medical care for psychiatric patients. PMID- 4025641 TI - Use of guanabenz in methadone withdrawal. PMID- 4025642 TI - A "gratuitous" conclusion on ECT. PMID- 4025643 TI - Diazepam in the treatment of hallucinations. PMID- 4025644 TI - The unreal real and the really unreal. PMID- 4025645 TI - Smoke detector legislation: its effect on owner-occupied homes. AB - Montgomery County, Maryland was the first major jurisdiction to pass a law requiring smoke detectors in all homes. Smoke detector coverage in the county was evaluated five years after the law's implementation and compared to the coverage in neighboring Fairfax County, Virginia, which has no such law. Firefighters visited 651 randomly selected owner-occupied homes and tested each detector. While a similar percentage of homes in Montgomery and Fairfax counties complied with detector codes (42 per cent vs 44 per cent, respectively), Montgomery County had a significantly lower percentage of homes with no working detectors (17 per cent vs 30 per cent) and with no detectors at all (6 per cent vs 16 per cent). In general, Montgomery County residents complied with what they believed the law required, but lacked knowledge of the law's details. New homes where building codes required detectors and homes where owners assumed that detectors were required by law were likely to have working detectors. Analyses of 12 years of fire data suggest that as a county approaches complete detector coverage, the risk of residential fire deaths decreases. An essentially unenforced law seems to be obeyed because it conforms to community values. PMID- 4025646 TI - Estimates of C. immitis infection by skin test reactivity in an endemic community. AB - This report is a comparison of two delayed hypersensitivity skin test reagents, coccidioidin and Spherulin, available for detection of prior infection by Coccidioides immitis. Coccidioidin proved to be a somewhat more sensitive reagent (33.4 per cent positive, vs 29.6 per cent for Spherulin). This difference persisted in the subjects when grouped by age, sex, exposure history, or history of coccidioidomycosis. Skin test reactivity to both reagents declined with age. Independent of exposure history coccidioidin detected 7.3 per cent of the subjects who were not detected by Spherulin; Spherulin detected prior infection in only 3.5 per cent of the subjects not detected by coccidioidin. These results differ from those of previously reported studies. PMID- 4025647 TI - Motor vehicle related injury on the bridges between Montreal and the South Shore of the St. Lawrence River, 1978-1982. AB - The injury experience related to motor vehicle crashes on four bridges and one tunnel in Montreal, Quebec, Canada, from 1978 to 1982, are described. Particular attention is given to the Jacques Cartier Bridge, publicly perceived as being excessively dangerous. Data from the Quebec Automobile Insurance Board and police reports confirm an excess of deaths (19/34; rate ratio = 4.5) and severe injuries (69/109; rate ratio = 6.2) on the Jacques Cartier Bridge, and the association of 74 per cent of the fatalities and 64 per cent of the severe-injury cases on this bridge with a single curve. Crashes follow a consistent pattern; vehicles fail to negotiate the curve and strike vehicles moving in the opposite direction. The demonstrated association between crashes and design factors provides a basis for identifying effective remedial and preventive measures. PMID- 4025648 TI - Circumcision in the United States. AB - The circumcision status of boys aged 12 through 17 years (born from 1949 to 1958) from a sample cohort of the National Health Examination Survey (NHES) cycle III, conducted from 1966-70, was analyzed. Over three-fourths of the cohort had been circumcised, reflecting circumcision practices in the 1950s. Prevalence of circumcision was more common in Whites, in families with higher income, and higher educated heads of household. Circumcision prevalence was the lowest in the South and highest in the Midwest. More recent national data are not available. PMID- 4025649 TI - Causes of death among female chemists. AB - A mortality odds ratio analysis of cause of death among 347 White female members of the American Chemical Society (ACS) revealed a five-fold excess of suicide, notably by cyanide poisoning. Risk was also elevated for all cancers combined and for cancers of the breast, ovary, stomach, pancreas, and lymphatic and hematopoietic system. The excess breast and ovary cancer deaths were limited to unmarried women. PMID- 4025650 TI - Fluorides, facts and fanatics: public health advocacy shouldn't stop at the courthouse door. PMID- 4025651 TI - Auto seat belts: good prenatal, postpartum, and infant care. PMID- 4025652 TI - On rationing organ transplantation. PMID- 4025653 TI - Public health and the environment. PMID- 4025654 TI - Microbiologic indicators of health risks associated with swimming. PMID- 4025655 TI - When the frame is part of the picture. PMID- 4025656 TI - A prospective study of swimming-related illness. I. Swimming-associated health risk. AB - During the summer of 1980, both swimmers and nonswimmers were enlisted in a prospective epidemiological study to determine the relationship between swimming, water quality, and the incidence of illness. Results of 4,537 telephone follow-up interviews showed that crude morbidity rates were 69.6 per 1,000 swimmers versus 29.5 per 1,000 nonswimmers. Swimmers experienced respiratory ailments most frequently, followed by gastrointestinal, eye, ear, skin, and allergenic symptoms, respectively. PMID- 4025657 TI - A prospective study of swimming-related illness. II. Morbidity and the microbiological quality of water. AB - A prospective cohort epidemiological-microbiological study was carried out at 10 beaches in Ontario, Canada. Lake water and sediment samples collected at the beaches were analyzed for fecal coliforms, fecal streptococci, heterotrophic bacteria, Pseudomonas aeruginosa, and total staphylococci. Mean fecal coliform levels in the surface water of the lakes were within accepted guidelines. Bacterial densities were found to be approximately 10 times higher in the sediment than in the corresponding surface water samples. Morbidity among swimmers was shown to be related to staphylococcal counts, to fecal coliform levels, and, somewhat less strongly, to fecal streptococcal counts. Total staphylococci appeared to be more consistent indicators for predicting total morbidity rates among swimmers. PMID- 4025658 TI - Do the new Metropolitan Life Insurance weight-height tables correctly assess body frame and body fat relationships? AB - The 1983 Metropolitan weight-height tables include elbow breadth as a measure of frame size. Such tables assume that frame measures provide an estimate of fat free mass and have little or no associations with body fat. These assumptions were evaluated in 437 Canadian adults for six frame measures by their associations with total body measures of fat and fat free mass. All six frame measures were similarly correlated with fat free mass, even when associations with height were taken into account. Wrist and ankle breadths were not associated with total body fat, while shoulder, elbow, hip, and knee breadths were so associated. Thus wrist and ankle breadths satisfy the assumptions inherent in the frame-weight-height tables better than elbow breadth and the other frame measures investigated. PMID- 4025659 TI - An exploration of somatization among Asian refugees and immigrants in primary care. AB - The clinical records of Chinese, Filipino, Vietnamese, Laotian, and Mien patients in primary care were reviewed to determine the prevalence of somatization, its associated patient characteristics, and the manifested illness behavior. Patients in this study were generally poor, unemployed, and spoke little English. Somatization accounted for 35 per cent of illness visits. These visits were also more costly. Refugees had a higher rate of somatization (42.7 per cent) than immigrants (27.1 per cent). Although sociodemographic characteristics did not strongly differentiate patients with somatization from others, ethnicity and indicators of decreased resources such as large households with low income, households headed by single women, or a limited English proficiency were associated with somatization in certain ethnic groups. Somatization is thus an important health problem among Asian refugees and immigrants. PMID- 4025660 TI - Health care attitudes and experiences during gynecologic care among lesbians and bisexuals. AB - Bisexuals (N = 424) and lesbians (N = 1,921) were surveyed regarding their sources of gynecologic care, utilization patterns, openness with physicians, and assessment of quality of care. About 40 per cent of each group believed that physician knowledge about their sexual preference would hinder the quality of medical care and about as many believed that it would have no effect. About one third in each group had not disclosed their sexual behavior although they desired to do so. Physicians rarely requested this information. A lesbian physician was overwhelmingly preferred for gynecologic care (96 per cent), particularly for problems with sexual functioning. Previous satisfaction with gynecologic care was most often described as "adequate," but almost as often as "variable" and "poor." Data suggest that quality, utilization, and medical outcomes of gynecologic care to this group would be improved if physicians would communicate greater awareness of sexual orientation in a nonprejudicial manner and ensure confidentiality. PMID- 4025661 TI - Premarital rubella vaccination program. AB - A two-year Vermont program identified 494 (7 per cent) of 6,982 premarital female serologies that were seronegative (less than 1:8) to rubella by hemagglutination inhibition (HI) titer. All 494 susceptible patients and their physicians were notified of their results by letter. The State Health Department received reports that a total of 194 (39 per cent) of the susceptible patients had received rubella vaccinations as a result of their notifications. Intensive follow-up of susceptibles appears to be important factor in the success of premarital rubella screening programs. PMID- 4025662 TI - Leptospiral exposure in Detroit rodent control workers. AB - Antibody levels to L. icterohemorrhagiae of rodent control workers and two control groups were compared with antibodies against five other leptospiral serotypes carried predominantly by species other than rats. Rodent control workers contact urban rats, 77 per cent of which are carriers of leptospiral organisms. Rodent control workers had higher antibody levels against L. icterohemorrhagiae than control groups (OR 4.37, 99 per cent CI = 3.0, 6.3 and OR 11.08, 99 per cent CI = 5.6, 22). Antibodies against the other five serotypes were almost non-existent in the study group. PMID- 4025663 TI - The prevalence of Toxocara species ova in backyards and gardens of Baltimore, Maryland. AB - Toxocara species ova were found in 16 of 146 (11 per cent) soil samples collected from backyards and gardens of private residences within Baltimore City. The recovery rate of parasite ova was similar for households regardless of their grouping by pet ownership characteristics or the presence of visible animal feces. The findings demonstrate the common occurrence of these eggs in locations likely to be important in the transmission of visceral larva migrans. PMID- 4025664 TI - A seroprevalence survey of hepatitis B markers among Haitians in a southwest Florida farming community. AB - We determined the seroprevalence of hepatitis B virus markers among 123 Haitian mothers and children in a southwest Florida farming community. Fifty-five per cent of mothers had one or more markers including two who were HBsAg positive. Only seven (10 per cent) children had markers; none were HBsAg positive. Pregnant Haitian women should be screened for HBsAg and infants born to those who are positive should receive immunoprophylaxis. Medical, dental, and laboratory workers caring for Haitian patients should also receive hepatitis B vaccine. PMID- 4025665 TI - Killing with kindness: why the FDA need not certify drugs used for execution safe and effective. PMID- 4025666 TI - In utero immunization of the fetus to tetanus by maternal vaccination during pregnancy. AB - We tested 36 pairs of umbilical cord blood and maternal sera collected at the time of delivery by radioimmunoassay and by Western blot analysis for IgG or IgM antitetanus antibodies (anti-TT). Twenty-one participants had received a recall injection of tetanus toxoid at various periods during pregnancy. Maternal vaccination in the last trimester of pregnancy was associated with the presence of IgM anti-TT in the cord blood sera; these were not detected in neonatal sera from mothers who were not vaccinated during pregnancy or who received the booster injection during the first two trimesters of gestation. The results could not be ascribed to artifacts such as the contamination of neonatal sera by maternal blood, the contamination of the anti-IgM antisera by antiidiotypes, or by the presence of neonatal IgM rheumatoid factor binding to immune complexes made of maternal IgG anti-TT and radiolabelled TT. Hence, it is concluded that maternal vaccination during the last trimester of pregnancy may induce in utero active immunization of the fetus. PMID- 4025667 TI - Immunoregulatory activities of human trophoblasts mediated by polyamine complexes. AB - In a previous publication we described the presence in human placenta (HP) of immunosuppressive factors inhibiting the lymphoproliferative responses to mitogen. The results of further study reported herein indicate that the substance involved is of a syncytiotrophoblastic origin, that it is thermostable to 100 degrees C for 1 hr, and of low molecular weight, i.e. 3,500. It was defined as a polyamine conjugate with nucleic acids. Trophoblast cell extracts lost their immunosuppressive ability after heating in cultures of human lymphocytes supplemented with 5% autologous serum. These effects were, however, preserved both in cultures assayed in 5% fetal calf serum and in those to which purified polyamine oxidase (PAO) was added to autologous serum. Trophoblast cell extract was found to contain polyamine oxidases. Placental PAO can be inhibited by quinacrine a typical inhibitor of flavoprotein enzymes but not by isoniazid, an inhibitor of pyridoxal enzymes; this would suggest that the enzymes in human placenta are of a tissular rather than seric origin. The implication of these observations is that immunosuppression is mediated by oxidative products issued from an interaction between polyamine and polyamine oxidase in the syncytiotrophoblast cytosol. This interaction may constitute the basis for a local immunological barrier and may be involved in the protection of the fetus against maternal immune rejection. PMID- 4025668 TI - Effect of sperm antibodies in males on human in vitro fertilization (IVF). AB - The effect of sperm antibodies on the human fertilization process was evaluated by analyzing the Royal Women's Hospital in vitro fertilization (IVF) data. The results suggest that sperm autoantibodies, particularly those of IgA immunoglobulin class (determined by immunobead test (IBT] can interfere with IVF. Thus, in a group (n = 8) of couples where the male partner had 80% or more of his motile spermatozoa coated with IgG and IgA class sperm antibodies, an overall fertilization rate of only 27% (18/66 ova) was obtained. In contrast, in a group (n = 9) with positive IBT results, but with less than 80% of motile spermatozoa coated with IgA class antibodies, a normal fertilization rate of 72% (47/65 ova) was obtained. Three of these patients had 90% or more of their motile spermatozoa coated with IgG and less than 70% coated with IgA class antibodies. In this subgroup a good fertilization rate of 16/21 (76%) was obtained. Another observation derived from this investigation is that the oocytes that do fertilize in the presence of sperm antibodies can subsequently proceed with normal cleavage, implantation, and pregnancy. This provides a rationale for attempting to treat these patients by reducing the proportion of antibody-coated sperm in vitro for future IVF cycles. PMID- 4025669 TI - Clindamycin levels in reproductive tissues. AB - Clindamycin is widely used in a variety of obstetric and gynecologic infections. Despite in vitro and clinical evidence of activity against anaerobes, genital organ tissue levels resulting from intravenous administration of the drug have not previously been reported. Following a single intravenous infusion of 600 mg of clindamycin phosphate, tissue levels were determined in operative specimens obtained from ten women. Specimens of cervix, uterus, fallopian tube, and ovary were obtained, and mean Clindamycin levels for each site were: cervix, 2.63 micrograms/ml; endometrium, 5.58 micrograms/ml; myometrium, 2.39 micrograms/ml; fallopian tube, 2.96 micrograms/ml; and ovary, 3.74 micrograms/ml. The mean serum level was 6.26 micrograms/ml at the time of uterine artery interruption. The clindamycin concentrations at all sites exceeded the usual therapeutic minimal inhibitory concentration, substantiating the usefulness of clindamycin in obstetric and gynecologic anaerobic infections. PMID- 4025670 TI - Effect of transfer factor on tumor-associated immunity and tumor growth of the Dunning R-3327G rat prostate adenocarcinoma. AB - Of importance in the design and application of improved or new modalities of treatment are their evaluation on relevant animal models. In the case of prostate cancer (PCa) the Dunning R-3327 rat prostate adenocarcinoma (PCa), and its variant sublines, is one such experimental tumor model of its human counterpart. In a preliminary study, the effect of transfer factor (TF), one form of passive immunotherapy, on tumor-associated immunity (TAI) and tumour growth and histology of the G subline (a poorly differentiated, fast-growing, androgen sensitive, and poorly metastatic tumour of the Dunning R-3327 rat PCa) has been evaluated. TF prepared from the leukocytes of tumor-bearing animals and nontumor-bearing animals referred to as sensitized (STF) and unsensitized (UTF), respectively, had no significant effect on TAI or tumor size. The only noticeable effect of TF in this study was the presence of variable and moderate lymphocytic infiltrates, necrosis, and degenerative-type cells in tumors of animal recipients of STF. The failure to observe significant differences in TAI among tumor bearing and nontumor bearing animals raises doubt in part, of the immunogenicity of the G subline tumor and its appropriateness, at least for subsequent immunological studies. Further factors considered in this regard, are questions of tumor load, including the possible need for the use of adjuvant, and the parameters and sensitivity of immune responsiveness selected for evaluation and immunocompetency. Subsequent evaluation of the effect of TF on other more immunogenic variant sublines of the Dunning R-3327 rat tumor may yet provide further and more useful information. PMID- 4025671 TI - Intrauterine growth retardation of unknown etiology. I. Serum complement and circulating immune complexes in mothers and infants. AB - Complement (C) and circulating immune complexes (CIC) levels were measured in 22 full-term pregnant women and 15 of their small-for-gestational-age (SGA) offspring in order to seek evidence supporting an immunological etiology for placental lesions related to idiopathic intrauterine growth retardation. We used 19 normal full-term pregnant women and 18 of their infants with birthweight above the 25th centile of the ponderal curve as a control population for this study. C levels were significantly lower in mothers of SGA infants than in controls (146.6 +/- 46.6 and 183.6 +/- 36.6 respectively, p less than 0.01). CIC were present in the sera of 5 out of 22 mothers of the SGA group and in 3 out of the 15 infants sera. No CIC were found in the sera of mothers or infants from the control group. Placental lesions were observed in 14 out of the 22 (64%) cases studied in the SGA group and in 1 of 11 (9%) of the controls. Two placentas from SGA infants showed acute atherosclerosis, and deposits of IgM and C3 were found in their vessel walls. These data are in favor of an immunological mechanism for intrauterine growth retardation of unknown etiology. PMID- 4025672 TI - Anterolateral dislocation of the head of the fibula in sports. AB - Traumatic anterolateral dislocation of the fibular head is an uncommon sports injury which is easily overlooked. Seventeen cases have been collected during private practice over the years. The typical mechanism of injury is a fall on the affected flexed knee with the leg adducted under the body and the ankle inverted. On physical examination there is an obvious bony prominence laterally of the fibular head and varying disability with activities; there is no significant effusion or signs of internal knee derangement or instability. Comparison identical radiographic views are necessary to confirm the diagnosis: on the anteroposterior view the fibular head is displaced laterally and the proximal interosseous space is widened; on the lateral view there is a greater overlap of the fibula on the tibia on the affected side. Peroneal nerve and ankle injuries can occur concomitantly with anterolateral proximal tibiofibular dislocation. Treatment options are closed or open reduction acutely and local strapping or fibular head resection for chronic cases based upon time of presentation and disability. PMID- 4025673 TI - Biomechanics of baseball pitching. A preliminary report. AB - Fifteen professional major league pitchers were filmed with high speed cinematography. One hundred forty-seven pitches were analyzed using an electromagnetic digitizer and a microcomputer. Three phases of throwing were studied: cocking, acceleration, and follow-through. The cocking phase is the period of time between the initiation of the windup and the moment at which the shoulder is in maximum external rotation. This phase occurs in approximately 1500 ms, and the shoulder is brought into an extreme position of external rotation. The acceleration phase and the initial stages of the follow-through phase produce extraordinary demands on the shoulder and elbow. The acceleration phase begins with the throwing shoulder in the position of maximum external rotation and terminates with ball release. This phase occurs in approximately 50 ms, and peak angular velocities averaging 6,180 deg/sec for shoulder internal rotation and 4,595 deg/sec for elbow extension were measured. The follow-through phase begins at ball release and continues until the motion of throwing has ceased. This phase occurs in approximately 350 ms. PMID- 4025674 TI - Rehabilitation of the pitching shoulder. AB - Shoulder pain is a common complaint among baseball pitchers. Frequently, the nature of shoulder pathology can be traced to lack of flexibility and muscular imbalance. This paper describes: the normal biomechanics of a properly functioning shoulder during a baseball pitch, pathomechanics of shoulder problems, flexibility requirements of the throwing shoulder, and the muscular balance necessary for an effective throwing shoulder. Appropriate examination procedures are described along with remedial exercises which ensure normal glenohumeral motion and integrated muscle action. PMID- 4025675 TI - Osgood-Schlatter's disease in adolescent athletes. Retrospective study of incidence and duration. AB - During the period of 1976 to 1981, a total of 412 young athletes contacted the Turku Sports Medical Research Unit's (TSMRU) Outpatient Sports Clinic with 586 complaints. These records included 68 athletes with Osgood-Schlatter's disease (OSD), who were initially prescribed an average of 2 months' rest from any physical activity causing pain. Symptoms of tibial tuberosity pain occurred first at the average age of 13.1 years. According to the retrospective questionnaire, the pain caused complete cessation of training for an average of 3.2 months, and the disease interfered with fully effective training for an average of 7.3 months. According to a retrospective questionnaire given to 389 students (191 girls and 198 boys), 50 (12.9%) had suffered from OSD. Nearly one-half of the students, 193 (49.6%), had been active in sports at the age of 13, and 41 (21.2%) of them had suffered from OSD. In those students who were not active in sports, the incidence was only nine (4.5%; P less than 0.001). The incidence (32%) was higher in the siblings of the OSD patients of TSMRU who were active in sports than in the corresponding student group (21.2%). In a group of 22 patients from the TSMRU who had suffered from Sever's disease (calcaneal apophysitis), the incidence of OSD (68%) was significantly higher than in students who were active in sports (P less than 0.001). PMID- 4025676 TI - Shock absorption characteristics of running shoes. AB - The change in shock absorption properties of running shoes was evaluated as a function of miles run. Different models of running shoes encompassing a wide range in retail price were obtained and mechanically tested to simulate the repeated heel strikes of running. The energy absorbed by the shoes was determined from the area under the load deformation curve at the equivalent of 0, 5, 10, 25, 50, 75, 100, 125, 150, 200, 250, 300, and 500 miles of running. Shoes were also tested at similar intervals after having been worn by volunteers during normal training. An approximate 33% difference in the initial shock absorption was observed in the different shoe models. In general, the shoes retained approximately 75% of their initial shock absorption capability after 50 miles of simulated running, and approximately 67% after 100 to 150 miles. Between 250 and 500 miles the shoes retained less than 60% of their initial shock absorption capacity. No differences in shock absorption characteristics were apparent based upon either shoe price or the manufacturer model. The results of shoes tested by the volunteer runners also showed a marked reduction in shock absorption with mileage. The loss, however, was not as great as in the machine-simulated running, with approximately 70% of initial shock absorption retained at 500 miles. PMID- 4025677 TI - Anteroposterior tibiofemoral displacements during isometric extension efforts. The roles of external load and knee flexion angle. AB - Rehabilitation of knee extensors is a major consideration in patients with cruciate injuries and repairs. Extension exercises, however, can produce undesirable loads on the injured or replaced anterior cruciate ligament (ACL) resulting in permanent stretch of this restraint. Our study measures the tibiofemoral displacements associated with proximal, middle, and distal locations of the external resisting force and knee flexion angles of 30 degrees, 60 degrees, and 90 degrees. Our results show that tibiofemoral displacements are dependent on both location of the external resisting force and knee flexion angle, with anterior displacements being associated with distal displacement of the resistance pad. The results suggest that patients with ACL injuries or repairs conduct extension exercises with a proximal position of the resistance pad to minimize loads and prevent stretching of this constraint. PMID- 4025678 TI - Improvement of muscle flexibility. A comparison between two techniques. AB - Forty-seven male subjects were randomly assigned to 4 different groups. Three groups of 10 subjects trained three times a week with a modified contract-relax (CR) method for improving muscle flexibility. Seventeen subjects trained during the same time with a traditional ballistic stretch (BS) method. After 30 days (14 training sessions) the latter group switched over to the CR method. The results showed that the CR method was significantly better than the BS method for improving muscle flexibility in the four different, bilateral muscle groups studied. After the initial 30 days the three groups of 10 subjects trained one, three, and five times a week, respectively, for another 30 days. The results showed that once a week was enough to maintain improved flexibility, while three and five times a week increased it further. The former BS group improved muscle flexibility between the 30th and 60th day, as expected from the results of the initial 30 days with the three CR groups, when training with the CR method three times a week. PMID- 4025679 TI - "Effort" thrombosis of the subclavian vein in a competitive swimmer. AB - "Effort" thrombosis is a unique form of subclavian and axillary vein thrombosis because it is the result of an unusual variant of the thoracic outlet syndrome. Another cause of subclavian vein thrombosis is local compression from trauma, tumor, or development anomalies; a third is intimal damage from indwelling central venous catheters. This is a case report of "effort" thrombosis of the subclavian vein in a competitive swimmer. A recently developed technique of local infusion of low-dose streptokinase therapy is used for clot lysis. Early diagnosis is essential for effective thrombus dissolution with streptokinase. The rationale, risk, and method of streptokinase administration are discussed. Since "effort" thrombosis is secondary to thoracic outlet syndrome (TOS), decompression of the thoracic outlet by removal of the first rib after clot lysis is recommended. PMID- 4025680 TI - Correction of abduction. Deformity of the small finger caused by avulsion of the insertion of the third volar interosseous muscle. AB - Wartenberg described the clinical sign of the abducted extended small finger that can result from ulnar nerve palsy. When this sign occurs in ulnar nerve palsy, it is a result of imbalance created by paralysis of the third volar interosseous muscle allowing the extensor digiti minimi to abduct the small finger as the finger is extended. If the third volar interosseous muscle is traumatically avulsed at its insertion and the ulnar nerve is intact, the abductor digiti minimi manus is an additional deforming force. PMID- 4025681 TI - Stress fracture of the ipsilateral first rib in a pitcher. AB - This stress fracture of the left first rib in a 17-year-old, left-handed high school baseball pitcher represents the first of its type reported in the literature. Two similar cases have been reported in pitchers, but the fracture was on the nondominant side in both cases. In contrast to most cases of this rare lesion, the stress fracture we report occurred acutely and was documented roentgenographically from onset to complete healing 9 months later. PMID- 4025682 TI - Terminology of sports. PMID- 4025683 TI - Inability of Plasmodium knowlesi sporozoites to invade Anopheles freeborni salivary glands. AB - Oocysts of Plasmodium knowlesi developed normally on the gut of the mosquito Anopheles freeborni, rupturing and releasing sporozoites at 10-14 days post infection. Subsequently, however, sporozoites were never found in this mosquito's salivary glands. Heterologous transplants of whole salivary glands from uninfected An. freeborni and An. dirus, a completely susceptible mosquito, into the abdomens of insects heavily infected with mature oocysts were done. Sporozoites failed to infect An. freeborni glands implanted in An. dirus but did enter An. dirus glands implanted in An. freeborni. These experiments suggest that P. knowlesi sporozoites are unable to recognize An. freeborni glands. PMID- 4025684 TI - Mucocutaneous leishmaniasis in Colombia: Leishmania braziliensis subspecies diversity. AB - It is generally held that with rare exception Leishmania braziliensis braziliensis is the parasite responsible for the metastatic development of mucocutaneous leishmaniasis in the New World. Yet the infrequency of mucocutaneous disease compared with cutaneous manifestations, and the difficulty of isolating parasites from mucocutaneous lesions have restricted the study of the organisms involved. We here report the biologic, isoenzymatic, and monoclonal antibody specificity characteristic of eight Leishmania isolates obtained from the mucosal lesions of the same number of patients. Individually and collectively, the identifying criteria implicate at least two L. braziliensis subspecies as etiologic agents of mucocutaneous leishmaniasis in Colombia and suggest that a spectrum of intrinsically distinguishable organisms may be involved in this disease form. PMID- 4025685 TI - A field method for the procurement of infective larvae of Onchocerca volvulus. AB - Natural vectors of onchocerciasis (S. yahense) were collected. Ninety-eight were intrathoracically inoculated with 30 freshly obtained skin-dwelling microfilariae. Of the 82 flies dissected, 56 were infected and 28 harbored infective larvae. A total of 193 infective O. volvulus larvae were obtained. The mean infective worm burden was 6.9. PMID- 4025686 TI - Comparative toxicity of purified human eosinophil granule cationic proteins for schistosomula of Schistosoma mansoni. AB - The human eosinophil granule contains several distinctive cationic proteins that have been purified to homogeneity, including major basic protein (MBP), eosinophil cationic protein (ECP), and eosinophil-derived neurotoxin (EDN). Two earlier studies have shown that MBP and ECP both damage schistosomula of Schistosoma mansoni in vitro in a dose-dependent fashion. The present study expands upon these observations by comparing the toxicity of MBP, ECP, as well as EDN when tested at equimolar concentrations (0.03-2 X 10(-5) M). On a molar basis, ECP was 8 to 10 times more potent than MBP, and the ECP-mediated killing of schistosomula was qualitatively different than that of MBP. Purified ECP produced complete fragmentation and disruption of schistosomula, whereas MBP produced a distinctive ballooning and detachment of the tegumental membrane. In contrast, EDN was only marginally toxic at high concentrations and caused crinkling of the tegumental membrane. Heating MBP and ECP for four hr at 56 degrees C caused precipitation and loss of toxicity for MBP, but not for ECP. Native MBP (with reactive sulfhydryl groups intact) and stabilized, reduced and alkylated MBP had comparable toxicity. To determine the relative contribution of MBP, ECP and other potentially helminthotoxic eosinophil granule constituents to schistosomulum damage, fractions of acid soluble granule extracts prepared by chromatography on Sephadex G-50 columns were analyzed for toxicity to schistosomula and for MBP and ECP levels by radioimmunoassay. Schistosomula were killed by fractions containing MBP, and to a much lesser and more variable extent by fractions containing EDN and a 21,000 dalton protein, but not by fractions coincident with the elution of ECP, which contained concentrations of ECP below that required to produce significant killing of schistosomula by the purified protein. Therefore, although ECP is a more potent helminthotoxin for schistosomula than MBP on a molar basis, MBP, by virtue of its abundance in the granule, accounts for the bulk of the toxicity in fractions of acid solubilized granules obtained from eosinophils of patients with marked eosinophilia. PMID- 4025687 TI - Eighteen-month follow-up on the treatment of urinary schistosomiasis with a single dose of metrifonate. AB - Egg excretion of school children with urinary schistosomiasis treated with a single 10 mg/kg dose of metrifonate was monitored over a period of 18 months. At 18 months 68.8% of infected children showed a greater than 90% reduction in egg excretion and 23.7% had ceased excreting eggs. During the study period 25% of children with no evidence of infection at the start of the trial had become infected, while 45.5% of children apparently cured by the metrifonate treatment had recommenced egg excretion. The evidence suggested that reinfection rather than recovery of adult worms was responsible. Children with scanty or light infections, in general, showed increasing egg excretion rates during the following period, while those with heavy or severe infections showed a sustained reduction. In view of this, single dose metrifonate may be a useful approach to mass treatment in a schistosomiasis control program, resulting in significant reduction in egg excretion in those most likely to be important sources of transmission. PMID- 4025688 TI - Stimulation of Schistosoma mansoni oviposition in vitro by animal and human portal serum. AB - Coupled adult pairs of Schistosoma mansoni were incubated in medium containing either peripheral or portal serum from rat, rabbit, hamster or humans. Daily egg production was measured. In all cases egg production was significantly increased for pairs in the presence of portal sera compared with that in the presence of peripheral sera. Fractionation of rabbit portal serum according to molecular weight demonstrated that the most active component(s) were in the range of 2,000 to 50,000. These fractions were as effective in stimulating oviposition as whole portal serum. CONCLUSIONS: 1) portal serum factor(s) that stimulate S. mansoni oviposition are present in susceptible and non-susceptible hosts; 2) the molecular weight range for the active components is larger than would be expected for simple carbohydrates, amino acids or free fatty acids absorbed from the gastrointestinal tract. PMID- 4025689 TI - Effect of plasma mebendazole concentrations in the treatment of human echinococcosis. AB - High oral doses of mebendazole were given for a mean period of 23 months to 22 patients with inoperable alveolar or cystic echinococcosis (Echinococcus multilocularis n = 18, E. granulosus n = 4). Clinical, morphological, biochemical and serological findings and plasma mebendazole levels were monitored. Clinical and biochemical improvement or stabilization was observed in 17 patients but the parasitic lesions did not decrease in size in most instances. One patient died shortly after onset of therapy with hemorrhage of esophageal varices. Three patients with alveolar and one with cystic echinococcosis had evidence of progressive disease such as increase of cholestasis, destruction of lumbar vertebrae and growth of an intraperitoneal cyst. The plasma mebendazole levels (4 hr after the morning dose) of the latter 4 patients were 0.09 +/- SD 0.02 mumol/l, while in those with clinical stabilization or improvement it was 0.30 +/ SD 0.14 mumol/l (P less than 0.001). These preliminary data indicate 1) a good clinical response to chemotherapy in most patients despite unchanged size of the parasitic lesions, and 2) a direct correlation of clinical response with plasma mebendazole levels. PMID- 4025690 TI - Pathological and parasitological aspects of the first autochthonous case of human paragonimiasis in Venezuela. AB - A worm found in histopathologic sections of a lung piece of a young Venezuelan male was identified as a Paragonimus sp. Definitive identification of the species was not possible since only a deteriorated segment of the worm was recovered, nevertheless comparison with other known species is discussed. This is the first report of an indigenous case of human paragonimiasis in Venezuela. PMID- 4025691 TI - A field study of paragonimiasis in Venezuela. AB - In a natural focus of paragonimiasis in the northeastern region of Venezuela, 130 people were clinically, parasitologically and immunologically evaluated. A specific intradermal test was positive in 13%. Besides an index case, three other active cases of paragonimiasis were identified. Adult Paragonimus worms and metacercariae were recovered from Didelphis marsupialis and Eudaniela garmani, respectively. Previous reports of Paragonimus infection in Venezuela are discussed. PMID- 4025692 TI - Seasnake bites in a freshwater lake. AB - One species of venomous seasnake, Hydrophis semperi, is found in Lake Taal, a large freshwater lake in the Philippines. The first series of seasnake bites occurring in freshwater is described. In one small fishing village, there were eight definite bites and one probably attributable death. In three of the eight patients, specific antibodies to Hydrophis venom were demonstrated. In contrast to previous seasnake studies, there was an absence of asymptomatic cases. The possible public health importance of freshwater seasnake bites in the Philippines needs further investigation. PMID- 4025693 TI - Continuous propagation of Ehrlichia sennetsu in murine macrophage cell cultures. AB - Ehrlichia sennetsu, the etiologic agent of human sennetsu rickettsiosis was successfully propagated in a continuous cell culture using murine cell lines P388D1 and Raw 264. Pleomorphic cytoplasmic inclusion bodies similar to Ehrlichia canis morulae were observed 3-4 days after second post-inoculation split. In the Raw 264 cell line E. sennetsu was not seen until the third passage. Relatively heavier infection was observed in P388D1 than in Raw cell line. The latter reached a maximum of 15% infection whereas P388D1 cell line attained saturation. Structural details of the organism were confirmed by electron microscopy. A unique rippled cell mass surrounding the plasma membrane was observed. Supernatants of cultures were shown to contain infectious organisms. The advantages of propagating E. sennetsu in continuous cell lines are discussed with respect to future physiochemical and immunochemical studies of this organism. PMID- 4025695 TI - Studies on the transmission of Venezuelan equine encephalitis virus by Colombian simuliidae (Diptera). AB - The ability of Simulium mexicanum and Simulium metallicum to serve as biological or mechanical vectors of an enzootic and an epizootic strain of Venezuelan equine encephalitis (VEE) virus was examined. Guinea pigs were inoculated with the epizootic Cordoba strain or the enzootic RPVP407 strain of VEE virus. Wild-caught adult Simuliidae were fed on the viremic guinea pigs and the virus content of groups of flies was determined at daily intervals post-engorgement to test for viral replication. Flies were refed on suckling mice at greater than or equal to 8 days post-engorgement to test for biological transmission. Other flies were interrupted while feeding on viremic guinea pigs and refed on suckling mice to test for mechanical transmission. Neither S. mexicanum nor S. metallicum appear to be efficient vectors of either strain of VEE virus, although occasional mechanical transmission was obtained. Titers of virus in flies decreased rapidly after engorgement and from 3-12 days post-engorgement virus was detected only in 5%-25% of both species of flies. Although earlier field evidence implicated both S. mexicanum and S. metallicum as vectors of epizootic VEE, we conclude that it is highly unlikely that they play an important role as vectors of the virus in nature. PMID- 4025694 TI - Ecologic observations of Venezuelan encephalitis virus in vertebrates and isolations of Nepuyo and Patois viruses from sentinel hamsters at Pacific and Atlantic habitats in Guatemala, 1968-1980. AB - La Avellana and Puerto Barrios, two enzootic foci of Venezuelan encephalitis (VE) virus on the Pacific and Caribbean lowlands (respectively) of Guatemala have been studied over a 13-year period. Data from sentinel hamsters and guinea pigs and wild and domestic vertebrates are reported. VE virus strains were isolated from hamsters each period they were exposed during the rainy seasons 1968-1980 and at the end of the dry season 1974. Rates of isolation of VE virus ranged from 0.2% 5.7% hamster/days/exposure. All strains tested were free of epizootic virions. Although virus was isolated from sentinel guinea pigs, their deaths were not attributable to infection with VE virus. Antibody titers in 26 of 28 terrestrial mammals bled at La Avellana in 1971 were higher to enzootic than to epizootic VE strains. Thirty-seven percent of 109 residents of Puerto Barrios had antibody to VE virus. In 13 of 20 tested, antibodies were engendered by the enzootic strain. Nepuyo and Patois viruses were isolated from sentinel hamsters at both La Avellana and Puerto Barrios. PMID- 4025696 TI - Case report of a patient having Schistosoma japonicum cerebritis and resolution of CAT brain scan abnormalities without specific antiparasitic therapy. PMID- 4025697 TI - Arterialized venous perfusion of composite tissue. AB - The results of our experiment prove that arterialized venous perfusion is a viable means of nourishing complex composite tissue without using the arterial tree. Previous laboratory findings, coupled with the results of this experiment, demonstrate that as long as proximal arterial inflow is ensured, both the arterial and venous trees need not be intact to keep tissue alive. Rather, it seems that the prerequisites for tissue survival are that at least one of the two systems be intact and that there be sufficient inflow and outflow channels available. Whether these channels are arteries or veins is probably not important. The use of properly placed efferent or afferent arteriovenous fistulas allows one system to provide both physiologic functions. Whether the efferent arterial anastomosis stays open over the long term appears to be inconsequential. Survival is ensured by either direct perfusion with oxygen delivery through the venous tree or through the eventual ingrowth of recipient vessels into the flap by way of the delay phenomena. This perfusion technique is ideally suited for tissue with an inadequate arterial tree but with an intact venous system devoid of venous valves (most veins less than 1.5 mm in diameter). A well-vascularized recipient bed capable of providing vessel ingrowth into transferred tissue may be important in the case of delayed arteriovenous fistula occlusion secondary to intimal hyperplasia; therefore, further experimental study of these flaps must be undertaken before arterialized venous flaps can be recommended for placement in recipient sites compromised due to radiation, ischemia, diabetes, or other causes of small vessel disease in the recipient bed. Although efferent arteriovenous fistulas are currently used to provide arterialized venous perfusion in selected cases of end stage arterial occlusive and vasospastic disease, perhaps their greatest role is in the management of tissue transfer with an inadequate arterial tree. Much knowledge must be gained to understand the physiologic principles and requirements for optimal perfusion. Many questions are left unanswered. For example, in those arteriovenous fistulas that narrow or occlude secondary to neointimal hyperplasia or other causes, which channels (veins or arteries?) are used for perfusion during recipient vessel growth? Can intimal hyperplasia be reversed or prevented by drug therapy and would this be advantageous? Can venous valves be made incompetent so that this technique can be used for larger vessels?(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 4025698 TI - Endothelialization of human collagen surfaces with human adult endothelial cells. AB - Artificial vascular grafts are currently used to restore blood flow to ischemic tissue. Although the long-term patency of large diameter grafts is relatively acceptable, small diameter (less than 4 mm) grafts exhibit poor long-term patency rates. One technique to create a nonthrombogenic surface on artificial prostheses has been to seed with endothelial cells derived from autologous vessels. We have examined the interaction of human adult endothelial cells with the natural collagen surfaces presented by human amnion. Scanning electron microscopic evaluation revealed that human adult endothelial cells adhered rapidly to both the basement surface (collagen types IV and V) and interstitial surface (collagen types I and III) of amnion. However, the adherence of cells was significantly greater on the basement membrane surface. In addition, human adult endothelial cells rapidly formed close cell-to-cell interactions on basement membrane as compared with cells seeded onto the interstitial surface. These results suggest that seeding of endothelial cells onto artificial surfaces will be facilitated if the surface simulates the natural basement membrane to which endothelial cells natively adhere. PMID- 4025699 TI - Vein valve transplantation. AB - The vein valve transplantation has, in our experience, subjectively relieved symptoms in the majority of patients. More importantly, elevated venous pressure has been decreased in most patients. Thus, patients exhibiting signs of venous insufficiency syndrome as well as elevated venous pressure and proved valvular incompetence should be considered candidates for vein valve transplantation after an unsuccessful trial of medical management. PMID- 4025701 TI - Immediate, safe hemodialysis into arteriovenous fistulas created with a new tunneler. An 11 year experience. AB - It seems apparent that application of the tunneler has greatly facilitated the immediate use of graft arteriovenous fistulas. Most new patients admitted with end-stage renal disease have arteriovenous fistulas created, receive hemodialysis appropriately, and are discharged from the hospital within 2 to 4 days. In my experience, there was a significant decrease in the need for externally placed catheters or shunts. These 301 consecutive cases with relatively few early complications attest to the safety of immediate hemodialysis into graft arteriovenous fistulas created with this tunneler. PMID- 4025700 TI - Continuous ambulatory venous pressure for diagnosis of venous insufficiency. Preliminary report. AB - We have found that the venous pressure slope during minimal exercise is a sensitive measurement of venous disease. This parameter differed greatly in our two study populations. Due to increased venous pressure, venous insufficiency syndrome patients have a greater volume of pooled blood, which results in smaller pressure changes with each muscle contraction. In patients with incompetent valves, blood flows in a retrograde fashion in the vein, which leads to a higher steady state minimal pressure and notably to a decreased venous pressure slope. Venous pressure slope is a particularly sensitive measurement and a good prognosticator of venous insufficiency syndrome before symptoms become disabling to the patient. Our data indicate a strong correlation between venous pressure slope and venographic results. In fact, patients with abnormal venographic results invariably have demonstrated venous pressure slopes in the abnormal range. PMID- 4025702 TI - Ankle bypass: should we go the distance? AB - This report reviewed the results of 47 distal arterial reconstructions to or below the level of the malleolus. The operations were performed by the techniques of popliteal-to-distal bypass (20 procedures) and in situ bypass (27 procedures). Seventy-five percent of patients had gangrene of ischemic ulceration, and all procedures were performed for limb salvage. Seventy-three percent of all patients were diabetic. The patency rates for popliteal-to-distal bypass with reversed saphenous vein were 92 percent at 24 months and 57 percent at 60 months, with a limb salvage rate of 70 percent at 60 months; the patency rates for popliteal-to distal bypass with PTFE were 53 percent at 12 months and 0 at 36 months, with a limb salvage rate of 53 percent at 36 months; and the patency rate for in situ saphenous vein bypass was 96 percent at 24 months, with a limb salvage rate of 80 percent at 24 months. Early results are promising for ankle bypass using the techniques of popliteal-to-distal and in situ bypass. PMID- 4025703 TI - Thirty year experience with predictive lumbar sympathectomy. Method for selection of patients. AB - An office or bedside procedure to predict benefit from or contraindications to lumbar sympathectomy has been presented. Significant benefit and no instance of paradoxic gangrene occurred in an experience of more than 30 years with the test. This personal series of over 70 patients illustrates significant benefits, including healing of gangrenous digits, successful ray (transmetatarsal) amputation, and relief of ischemic rest pain in selected patients, even in the absence of femoral (groin) pulses. A criterion of an increase of 2 degrees or more in skin temperature of the ipsilateral great toe after lumbar sympathetic block at the approximate levels of the second, third, and fourth lumbar vertebrae has proved to be an adequate parameter or indication of subsequent benefit from surgical lumbar sympathectomy. A favorable response is predictable by the method described. PMID- 4025704 TI - Surgery, an international discipline. PMID- 4025705 TI - Ileal conduits for recurrent unresectable colorectal adenocarcinoma. AB - In a retrospective 4 year study, 19 patients with unresectable recurrent pelvic tumor secondary to colorectal adenocarcinoma underwent urinary diversion. An ileal conduit was performed for palliative purposes at the time of exploration. None of the 19 patients had evidence of distant metastases. Survival after the ileal conduit ranged from 2 to 26 months (median 13 months). This survival rate did not vary significantly according to sex or whether hydronephrosis resolved after urinary diversion. Postoperative complications developed in three patients. Two of these complications were ureterointestinal anastomotic leaks and the third was development of an enterocutaneous fistula. The quality of life was rated as good by 75 percent of the patients and fair by 18 percent, with all patients relieved of painful obstructive uropathy. Eighteen of 19 patients were able to resume useful and productive lives. PMID- 4025706 TI - Jejunal interposition for recurrent gastroesophageal reflux in children. AB - There is limited experience with surgical treatment for recurrent gastroesophageal reflux after an antireflux procedure. In four pediatric patients with recurrent reflux after surgical therapy, interposition of an isoperistaltic segment of jejunum produced excellent short-term results. Further follow-up is needed as experience broadens. At the present time, this procedure merits consideration in patients with recurrent gastroesophageal reflux. PMID- 4025707 TI - Use of the computerized tomographic scan in the diagnosis and treatment of abscesses. AB - Over a 5 year period, 89 patients underwent one or more computerized tomographic scans to locate an abscess during 92 hospitalizations. The scans were a most sensitive (93 percent), specific (98 percent), and accurate (96 percent) means of abscess detection. Thirty-nine patients had positive scans. Sixteen patients were treated directly by open surgical methods, 1 of whom required percutaneous drainage in the postoperative period for incomplete drainage. An additional 23 patients underwent attempted percutaneous abscess drainage. In 17 patients, drainage was successful. Five patients underwent percutaneous drainage and later required laparotomy, two of whom underwent unavoidable surgical procedures and three surgery for incomplete drainage. Overall, percutaneous abscess drainage was successful in 83 percent. Of 11 deaths, 8 occurred in the group with computerized tomographic scans negative for abscess. Three of these were false-negative scans. Three deaths occurred in the group with scans positive for abscess. All were of patients with hepatic abscesses treated by open surgical drainage, one after failed percutaneous drainage. Twelve patients had multiple organ failure, and 8 of these patients died, for a mortality of 67 percent. The computerized tomographic scan is the diagnostic procedure of choice in the diagnosis of abscesses. In selected patients, percutaneous abscess drainage is also a successful means of abscess treatment and avoids the complications of a laparotomy. The onset of multiple organ failure in the surgical patient should alert the diagnostician to the possibility of a septic focus. The role of early laparotomy in these patients is uncertain. We recommend early use of the computerized tomographic scan in the septic surgical patient. Prompt diagnosis and treatment of abscesses, whether by open or percutaneous routes, may avert the development of multiple organ failure and reduce morbidity and mortality. PMID- 4025708 TI - Role of vein patch angioplasty in isolated operations for profunda femoris stenosis and disabling claudication. AB - This report has described the treatment of disabling claudication by correction of profunda femoris artery stenosis. Vein patch angioplasty and endarterectomy with primary closure were the procedures used. An overall success rate of 71 percent was noted with no significant complications, however, the angioplasty group had a higher likelihood of success (83 percent versus 40 percent). They also were noted to have a significantly improved ankle-arm Doppler index, with a mean follow-up of 21 months. Possible explanations for these observations have been considered and technical recommendations discussed. PMID- 4025709 TI - Traumatic arterial injuries of the upper extremity: determinants of disability. AB - Of 233 patients who sustained vascular injuries during a 13 year period, 99 had involvement of the upper extremity. The primary site of upper extremity injuries was the brachial artery (43 patients), and the primary cause of injury was gunshot wounds. The majority of the vascular injuries were repaired primarily. Nerve injuries occurred in 56 of the patients, and they were the primary cause of disability. Edema and infection were not significant determinants of limitations in function. Gunshot wounds to the brachial artery resulted in the highest incidence of disability and limb loss. PMID- 4025710 TI - What do breast symptoms mean? AB - Breast symptoms of pain, tenderness, and engorgement correlate with objective findings of nodularity on physical examination. Like all other factors for breast disease, they are not a single determinant of diagnosis, as shown by the 3 X 3 contingency table, but they are a useful addition to our understanding. From the available data, symptoms seem as accurate as physical examination for evaluating changes in benign diseases. By extrapolation, we expect they will be useful for management of premalignant breast lesions. We conclude that a complete breast evaluation should include inquiry about breast symptoms and whether these symptoms have changed. PMID- 4025711 TI - Repair of long-term venous catheters. AB - The insertion of long-term Silastic catheters into the vena cava for home parenteral nutrition, antibiotic administration, and chemotherapy is increasing; however, one of the often described complications of these catheters is breakage of the external segment of the catheter. A new device as well as a new method for repair of the catheter has been described. Clinical testing of the catheters repaired with this device by our nutritional support service has demonstrated no leakage or occlusion at the catheter repair site. We believe the catheter repair kit described is simpler to use than the repair kit currently on the market. PMID- 4025712 TI - A simple technique of correcting complete gastric obstruction after gastric partitioning. AB - The use of autosuture staplers in intraabdominal surgery has become an accepted procedure for simplifying gastrointestinal surgery. Described in this report is a simple method of correcting unrelenting gastric obstruction that may occur after gastric partitioning for morbid obesity by utilizing the autosuture model EEA stapler to reestablish gastric continuity. PMID- 4025713 TI - Granuloma associated with fenestrated tracheostomy tubes. AB - Four cases of granuloma that caused tracheal obstruction have been presented. In each, although for different reasons, a tracheostomy was performed and a fenestrated tube inserted. We conclude that the insertion of a fenestrated tube was the direct cause of the excessive amount of granuloma that caused tracheal obstruction. PMID- 4025714 TI - New uses of fluorescence in the surgical management of necrotizing soft tissue infection. AB - The planning of incisions in the management of necrotizing soft tissue infections has largely been carried out by subjective methods. Because of disruption of the fasciocutaneous circulation, the perfusion of randomly based flaps is frequently tenuous. A method that provides safe, rapid, and accurate evaluation of tissue perfusion would therefore prove invaluable in the preoperative planning, as well as in the postoperative management of these infections. The digital dermofluorometer is a recently introduced instrument that objectively evaluates skin blood flow based on the cutaneous delivery of sodium fluorescein. We have used the technique successfully and without incident in patients who presented with necrotizing soft tissue infections. The theory, methods, and application of the test have been presented along with two case reports. PMID- 4025715 TI - Pneumopylephlebitis and intramesocolic diverticular perforation. AB - The insidious presentation of intramesocolic perforation in diverticulitis has been reviewed, and two cases of intramesocolic perforation associated with pneumopylephlebitis have been reported. Review of the two previously reported cases of pneumopylephlebitis associated with diverticular perforation suggests that these may have been intramesocolic perforations as well. Exploratory laparotomy is clearly indicated in cases of pneumopylephlebitis. In patients with recurrent sepsis without a probable source, a water-soluble contrast enema is recommended. If conservative measures fail, an exploratory laparotomy should be performed to exclude intramesocolic abscess. PMID- 4025716 TI - The surgical treatment of giant cell tumor of bone. PMID- 4025717 TI - Coronary artery vasoconstriction and its treatment with calcium channel blockers. PMID- 4025718 TI - NMR evaluation of the cardiovascular system. PMID- 4025719 TI - Spermatic vein occlusion as treatment for testicular varicoceles. PMID- 4025720 TI - Genetic counseling in families at increased risk for neural tube defects. PMID- 4025721 TI - The clinical and cytological assessment of tioconazole in vulvo-vaginal candidiasis. PMID- 4025722 TI - Immunotherapy of insulin-dependent diabetes. PMID- 4025723 TI - Periampullary disease and pancreatoduodenectomy. PMID- 4025724 TI - Kawasaki disease in an Alaskan Eskimo child. PMID- 4025725 TI - Uninsured doctors. PMID- 4025726 TI - An algorithmic method for histologic diagnosis of inflammatory and neoplastic skin diseases by analysis of their patterns. PMID- 4025727 TI - Subcutaneous fibroadenoma on an arm. AB - A case of a subcutaneous fibroadenoma on an arm of an 18-year-old woman is presented. The neoplasm, thought clinically to be a lipoma, may have arisen in ectopic breast tissue. Dermatologists and dermatopathologists should be aware that fibroadenomas histologically identical with those seen in the breast have been observed along the milkline and may also occur in other sites. PMID- 4025728 TI - Molluscum contagiosum may affect primarily the epidermis without involving hair follicles. AB - Lesions of molluscum contagiosum occur on palms and in skin tags. Their origin in places where there are no hair follicles proves that the epidermis itself may be infected by the causative poxvirus. The central umbilications of lesions are therefore not necessarily related to acrotrichia. PMID- 4025729 TI - Erythema multiforme. PMID- 4025730 TI - My concept of erythema multiforme. PMID- 4025731 TI - Erythema multiforme. A clinical syndrome and a histologic complex. PMID- 4025733 TI - Criteria for identifying vasculitis of small blood vessels by conventional microscopy. PMID- 4025732 TI - Chromatic fantasies. Color words in medicine. PMID- 4025734 TI - Civility among colleagues should be reciprocal. PMID- 4025735 TI - The field or Peterson system for the identification of birds. PMID- 4025736 TI - Ellenborough King's disease: an addendum to "chronic relapsing eponymy". PMID- 4025738 TI - Pustular bacterid of Andrews. PMID- 4025737 TI - Sebaceoma. PMID- 4025739 TI - [Morphological, histological and ultrastructural study of the olfactory mucosa. I. The olfactory epithelium]. PMID- 4025740 TI - [Olfactory neuroblastoma. Apropos of 2 cases]. PMID- 4025741 TI - [The innervation of the vocal muscles]. PMID- 4025742 TI - [Ultrastructural changes in the serous acini of the submandibular glands in castrated male Wistar rats]. PMID- 4025743 TI - Is asepsis still essential? PMID- 4025744 TI - Contamination of internal jugular cannulae. AB - 137 internal jugular vein cannulae from 113 patients undergoing open heart surgery were cultured using standard broth culture and a semiquantitative culture technique. 60 of the cannulae were placed using an aseptic technique and 77 using a standard non sterile technique. Significant contamination was found in 18.3% of the cannulae in the aseptic group and 15.6% in the standard group. The contaminating organism was Staphylococcus epidermidis in 87.1% of cases. No advantage in using an aseptic technique of cannula insertion was demonstrated. It was concluded that the major source of contamination was elsewhere. PMID- 4025745 TI - Cardiovascular effects of spinal subarachnoid anaesthesia. A study in patients with chronic spinal cord injuries. AB - Spinal anaesthesia using 1.2 ml of hyperbaric cinchocaine was found to abolish the autonomic hyper-reflexic cardiovascular responses to bladder distension and produced little alteration in cardiovascular measurements. PMID- 4025746 TI - Warming blood before transfusion. Does immersion warming change blood composition? AB - The practice of warming blood for transfusion by immersion in a water bath has been studied. Blood, 3 days after collection, with CPD-adenine anticoagulant, was warmed at 25 degrees C, 37 degrees C and 45 degrees C for up to 2 hours. The procedure was repeated after 2 and 4 weeks' storage at 4 degrees C. Only trivial biochemical and morphological changes resulted from warming. Within these limits, immersion warming of blood appears to be a reasonable alternative to using a blood-warming coil. Other aspects of immersion warming are discussed. PMID- 4025747 TI - Recovery from day-case anaesthesia. The effect of different inhalational anaesthetic agents. AB - Sixty unpremedicated patients undergoing dilatation and curettage were allocated randomly to receive one of three inhalational agents (halothane, enflurane or isoflurane) to supplement 67% nitrous oxide in oxygen after induction of anaesthesia with methohexitone. Recovery was assessed by the time patients took to open their eyes, to give their correct date of birth, to regain their pre operative level of manipulative skill with a children's postbox toy, and by comparing pre-operative and postoperative performance of a paper and pencil test (the p-deletion test). There was no difference in the time to open eyes or to regain their pre-operative score with the postbox whether the patients received halothane, enflurane or isoflurane. Patients in the isoflurane group took longer than patients in the enflurane group to give their correct date of birth, but they performed better in the p-deletion test postoperatively, completing more lines with the same number of errors. Patients receiving enflurane committed more errors postoperatively in the p-deletion test. The incidence of complications was low and was not influenced by the choice of inhalational agent. PMID- 4025748 TI - Intradermal testing and anaphylactoid reactions. The limitations of their use in the investigation of reactions to intravenous anaesthetics. AB - A patient who exhibited a severe reaction to an intravenous agent on one occasion was given a similar anaesthetic on a subsequent occasion without incident. Intradermal testing was carried out and the results are tabulated and discussed. PMID- 4025749 TI - If in doubt, take it out. Obstruction of tracheal tube by prominent aortic knuckle. PMID- 4025750 TI - Evaluation of the Datex 'Normac' anaesthetic agent monitor. AB - The Datex 'Normac' infrared anaesthetic agent monitor has been evaluated for accuracy of calibration, stability and speed of response. Accuracy was assessed by comparing with a gas chromatograph calibrated using volumetric standards and was found to be very good for isoflurane and enflurane but was slightly less accurate for halothane, due to a low signal: noise ratio. The stability of the instrument was found to be exceptionally good. The response time is dependent on the sampling rate and we found that, in practice, the instrument would record the end expired anaesthetic concentration on patients breathing up to 15 breaths/minute. The instrument is compact and convenient for use in operating theatres. PMID- 4025751 TI - The 'Permox' oxygen concentrator. Its mode of action, performance and potential application. AB - The performance of the 'Permox' oxygen concentrator has been investigated in detail with particular reference to its possible use as an alternative to conventional oxygen supplies both in the emergency situation, in the event of failure of pipeline or cylinder systems or when these are unavailable. The stability and concentrations of oxygen produced at various flows provided a viable alternative supply of oxygen, and the portability and reliability of this particular apparatus made it suitable for use in the many situations considered. PMID- 4025752 TI - A Venturi connector for tracheal tubes. AB - An attachment for tracheal tubes is described. It functions as a holder for a choice of needles used to conduct a Venturi jet powered from a high-pressure gas system of the kind used for bronchoscopic ventilation. It is suggested as a potentially useful device for some unusual clinical situations, two of which are illustrated. PMID- 4025753 TI - A nerve stimulator for peripheral nerve blockade. AB - An inexpensive, portable nerve stimulator is described which is easily constructed and may be used to enhance the ease and effectiveness of peripheral nerve blockade. PMID- 4025754 TI - Mortality following surgery for fractures of the neck of femur. AB - The mortality following surgery for hip fractures during 1982 is reviewed. 91 procedures were performed on 89 patients. The mortality rate at 4 weeks following general anaesthesia was 2.7%. This is much lower than previously reported. Possible reasons for the variation in mortality between this series and others, are discussed. PMID- 4025755 TI - Postoperative pain relief with naloxone. Severe respiratory depression and pain after high dose buprenorphine. AB - Buprenorphine 30 and 40 micrograms/kg was given as the sole intravenous analgesic in balanced anaesthesia to 12 patients undergoing cholecystectomy. Significant and severe respiratory depression was found 15 minutes after preoperative loading with buprenorphine. In the immediate postoperative period six patients were in pain. They were treated with naloxone 0.08-0.4 mg leading to a long lasting period of pain relief (median 22 hours). PMID- 4025756 TI - Anaesthetics and the immune response. PMID- 4025757 TI - Defensive medicine. PMID- 4025758 TI - Anaesthesia and Gilbert's syndrome. PMID- 4025759 TI - Epidural test doses in obstetrics. PMID- 4025760 TI - The problems of anaesthesia for a neonate with fused jaws. PMID- 4025761 TI - Emergency transtracheal ventilation in anaesthesia or the casualty department. PMID- 4025762 TI - Falsely positive reaction to glucose test strips. PMID- 4025763 TI - Rationale and experience with visual analogue toys. PMID- 4025764 TI - Foreign body. PMID- 4025765 TI - Not to be resuscitated. PMID- 4025766 TI - Controlled neck compression in neurosurgery. Studies on venous air embolism in upright sheep. AB - Bilateral compression of the jugular veins to raise temporarily cerebral venous pressure, is a manoeuvre recommended frequently in the immediate management of venous air embolism during neurosurgery. One method of compressing the neck veins is to inflate a pneumatic cuff secured around the neck with adhesive tape. This method of neck vein compression had been assessed in upright anaesthetised sheep and found to be an easily controlled and efficient way to raise the cerebral venous pressure. Advantages, dangers and potential problems associated with the use of an inflatable cuff in the clinical situation are discussed. PMID- 4025767 TI - Athletic dysrhythmias. A case report and review of the phenomenon of the 'athlete's heart'. AB - A 36-year-old athlete was anaesthetised for a minor surgical procedure. His heart rate fell to 30 beats/minute during the operation, the electrocardiogram showed A V junctional rhythm. Sinus rhythm of 58 beats/minute was restored by atropine 1.2 mg. His resting 12-lead electrocardiogram showed sinus bradycardia and features consistent with a diagnosis of 'athlete's heart'. A review is presented of the physiological and electrocardiographical features of this phenomenon. The current popularity of running as a leisure pursuit makes it important that anaesthetists recognise the peculiarities of the trained athletic heart. PMID- 4025768 TI - Anaphylactoid reaction to oxytocin in pregnancy. AB - A case of an allergic reaction to Syntocinon (synthetic oxytocin) administered during Caesarean section is reported. PMID- 4025769 TI - Wolff-Parkinson-White syndrome. Termination of paroxysmal supraventricular tachycardia with phenylephrine. AB - A patient with Wolff-Parkinson-White syndrome, susceptible to tachydysrhythmias , presented for eye surgery under general anaesthesia. He developed a supraventricular tachycardia refractory to a variety of treatments. Phenylephrine consistently abolished the dysrhythmia, probably by acting directly to stimulate the arterial baroreceptors and hence vagal output. Vasopressor therapy should be considered in Wolff-Parkinson-White syndrome tachyarrhythmias, when circumstances permit. PMID- 4025770 TI - Free-standing vaporizers. Another hazard. AB - A previously unreported hazard of free-standing 'Tec' type vaporizers relating to their positioning downstream of the oxygen flush is presented. Three Enfluratec Mark III vaporizers were studied; measurement of delivered enflurane concentration was performed at a flow rate of 8 litres/minute, during and after the application of the oxygen flush upstream of the vaporizer. The maximum difference between the dial setting and the measured vapour concentration occurred when a 5-second flush was applied to a vaporizer set at 0.2 volume %, the peak vapour concentration recorded being 2.3%. Other hazards of free-standing vaporizers are discussed and ways of avoiding these hazards considered. PMID- 4025771 TI - Anaesthesia for suction termination of pregnancy. AB - The effect of three anaesthetic techniques on blood loss and intra-uterine pressure changes in response to Syntocinon were studied in patients undergoing routine first trimester suction termination of pregnancy. All patients received a standard premedication, a bolus dose of fentanyl, intravenous induction of anaesthesia and maintenance with nitrous oxide and oxygen plus either intravenous supplementation or 0.5% halothane. Intra-uterine pressure was related to the anaesthetic technique used although blood loss was unrelated either to anaesthetic technique or to intra-uterine pressure changes. PMID- 4025772 TI - Mental function and morbidity after acute hip surgery during spinal and general anaesthesia. AB - Forty elderly patients (mean age 78.9 years) undergoing acute surgery for hip fracture were given at random either spinal analgesia with bupivacaine 0.75% or general anaesthesia with diazepam, fentanly and N2O/O2. Mental function was studied pre-operatively with an abbreviated mental test and 1 week and 3 months postoperatively in both groups. Mortality and number of complications was similar in the two groups, but a shorter time of ambulation was seen in the spinal group compared to the general anaesthetic group. No persistent impairment in mental function was found after acute hip surgery under spinal or general anaesthesia and the only advantage of regional technique was a shorter time of ambulation. PMID- 4025773 TI - Anaesthesia for translumbar aortography. AB - Fifty patients presenting for elective translumbar aortography were randomly allocated to one of two groups receiving either enflurane or isoflurane. Premedication was with oral lorazepam. The patients' tracheas were intubated and they were allowed to breathe spontaneously in the prone position during the procedure. There was no significant difference in heart rate during the investigation but there was a statistically significant fall in the blood pressure from its pre-induction level. Arterial oxygenation was adequate throughout the procedure. Arterial carbon dioxide tension was significantly lower in the isoflurane group at the beginning and at end of the procedure (p less than 0.01), but there was no significant change in carbon dioxide tension within the groups during the procedure. Spontaneous ventilation with enflurane or isoflurane is a satisfactory anaesthetic technique for translumbar aortography. PMID- 4025774 TI - The depth of the lumbar epidural space from the skin. AB - The depth of the epidural space at different intervertebral interspaces was measured in 1000 parturients. Overall the median distance from the skin to the epidural space was 4.7 cm, but this varied with the lumbar interspace at which it was measured, being greatest at the third (L3-4) interspace (4.93 cm) and least at the first (L1-2) interspace (4.23 cm). The clinical significance of these findings is discussed. PMID- 4025776 TI - Malignant hyperthermia--or not? PMID- 4025777 TI - The pre-operative visit: a source of anxiety. PMID- 4025778 TI - Unexpected artefact during spectral edge analysis. PMID- 4025775 TI - Indoramin-induced hypotension. An evaluation during ear, nose and throat surgery. AB - Indoramin, a competitive alpha 1-adrenoceptor antagonist, was administered intravenously to 12 fit patients aged 20-49 years during general anaesthesia with either halothane or enflurane for ear, nose and throat surgery. A mean decrease of systolic blood pressure of 6 mmHg followed the initial dose of 0.1 mg/kg. Systolic blood pressures of 70-80 mmHg were achieved in nine patients using 0.29 4 mg/kg. The maximum effect of every dose was achieved within 3 minutes, with a probable duration of action of at least 30 minutes. Large changes of heart rate did not occur, though there was gradual slowing of the heart during each series of incremental administrations. Junctional rhythm, sometimes with bradycardia and hypotension, occurred in five patients (four in halothane group; one in enflurane group). Because of this, and the greater than ten-fold variation in decrease of blood pressure for a single weight-related dose, indoramin is not recommended for the reduction of blood pressure during halothane anaesthesia. PMID- 4025779 TI - Hazards in multiple cannulation of a single vein. PMID- 4025780 TI - Sustained-release morphine for postoperative analgesia. PMID- 4025781 TI - Ketamine and bronchospasm. PMID- 4025782 TI - Alfentanil and isoflurane anaesthesia for day stay dental surgery. PMID- 4025783 TI - Modification of laryngoscope for nasogastric intubation. PMID- 4025784 TI - Splitting ratio. PMID- 4025785 TI - Koenig's tracheostomy tube; neglected but still useful. PMID- 4025786 TI - Multi-mode switchable breathing systems. PMID- 4025787 TI - A clear airway during tracheal surgery. PMID- 4025788 TI - Generalised oedema and epidural anaesthesia. PMID- 4025789 TI - Central venous and direct pressure monitoring. PMID- 4025790 TI - Amplification of oesophageal sounds. PMID- 4025791 TI - Anaesthesia for ENT surgery in children. PMID- 4025792 TI - [Aortofemoral bifurcation bypass--effect of anesthesia procedure (NLA, thoracic continuous catheter peridural anesthesia) on circulation, respiration and metabolism. Hemodynamic changes caused by peridural anesthesia and anesthesia induction]. AB - In 50 patients scheduled for infrarenal aortic bypass surgery the cardiovascular effects of two anaesthetic regimes were investigated prior to surgery. A Swan Ganz-catheter was used for haemodynamic measurements. These patients, having been randomized into two groups, were optimally volume loaded (PCWP 10 mmHg) before anaesthesia. In 24 patients a thoracic epidural was induced with 12-15 ml 0.25% plain bupivacaine. When segmental anaesthesia had extended from T4/5 to L1/2 general anaesthesia was additionally applied (flunitrazepam 1.5-2 mg, pancuronium bromide 0.1 mg/kg). In 26 patients neuroleptanaesthesia was induced (droperidol 0.1-0.2 mg/kg, fentanyl 0.01 mg/kg, pancuronium bromide 0.1 mg/kg, and thiopentone 100-150 mg. Haemodynamic measurements were made before injection into the epidural catheter, after complete spread of anaesthesia, before commencing general anaesthesia and 10-15 min thereafter. RESULTS: Neither of the two procedures were associated with severe haemodynamic alterations. In the epidural group HR fell slightly during latency of complete spread and increased to the same extend following general anaesthesia. The epidural caused MAP (104 to 88 mmHg), mean PAP (20 to 14 mmHg), PCWP (10 to 7.5 mmHg), and RAP (4.5 to 2.5 mmHg) to decrease moderately but no further changes were effected by the subsequent general anaesthesia. SVR and PVR were not influenced by either epidural or by general anaesthesia. CI (3.6 to 3.41 . min-1 . m-2), LVSWI (67 to 52 p . m-1), and cardiac minute work index (55 to 40 J . min-1 . m-2) decreased during latency of complete spread but were no further influenced by general anaesthesia. The haemodynamic changes of neuroleptanaesthesia were almost identical to those of the combined epidural-general anaesthesia. For the operation which followed, a continuous infusion of 0.125 per cent plain bupivacaine (0.25 ml/kg X h) via epidural catheter (in combination with N2O/O2-anaesthesia) was sufficient for complete analgesia in the epidural group. These findings lead to the conclusion that a small bolus volume and a low concentration of bupivacaine result in good anaesthesia while avoiding serious haemodynamic alterations. PMID- 4025794 TI - [Massive intraoperative lung embolism caused by the introduction of a telescope pin (Bailey-Dubow pin) in a child with osteogenesis imperfecta]. AB - We report the case of a massive pulmonary embolism in a three year old boy with osteogenesis imperfecta during a closed insertion of a Bailey-Dubow-rod. An increased intramedullary pressure with consecutive entering of medullary particles or air into the blood stream due to the insertion of the Bailey-Dubow rod is discussed as the cause of the pulmonary embolus. PMID- 4025793 TI - [Positive modification of hemodynamics in post cardiac surgery patients by hemofiltration. Improved method for the demonstration of myocardial depressant factor (MDF) in hemofiltrate]. AB - The method of haemofiltration was used in 29 postoperative cardio-surgical patients with low blood pressure, high left ventricular filling pressure and low total peripheral resistance, which did not respond to the use of the intraaortic balloon pump or pharmaco-therapy. In severe low-output syndrome hemodynamic parameters are: reduced mean arterial pressure, increased left ventricular filling pressure, increased mean arterial pulmonary pressure as well as significantly reduced total peripheral resistance [4-6, 28]. Inspite of pharmaco therapy, cardiac performance regarding peripheral perfusion is insufficient; this leads to a vicious cycle of irreversible O2-debt and severe cellular damage. After haemofiltration there was a significant improvement in the haemodynamic parameters, which in our opinion was due to the elimination of toxic peptides such as Myocardial Depressant Factor (MDF). In 27 of a total of 29 patients, haemodynamic parameters returned to normal after treatment. 19 patients were discharged, eight patients died after a number of days or weeks from causes not related to the original cardiogenic shock (cerebral embolism, reinfarction, myocardiopathy and pneumonia). PMID- 4025795 TI - [Intraoperative mechanical autotransfusion: examination of the withdrawn blood before retransfusion]. PMID- 4025796 TI - [High dosage thalamonal/rohypnol for premedication]. PMID- 4025797 TI - Collection and analysis of kinetic data from a stopped-flow spectrophotometer using a microcomputer. AB - A method of interfacing an inexpensive microcomputer to a stopped-flow kinetics spectrophotometer is described. It allows software-selectable sampling frequencies between 0.1 ms and 8 s and large numbers of data points to be collected. Machine language routines to use the interface are described and these allow the sampling frequency to be altered during data collection to ensure adequate numbers of points in critical regions of the kinetic profile. BASIC programs for collection and analysis of multicomponent kinetic data using this system are also described. Due to the large number of data points that can be collected and the ability to selectively sample transmittance values in regions where the signal is rapidly changing with time, relatively unsophisticated methods of data analysis can be used. These methods are suitable for use by microcomputers and mean that data analysis and acquisition can be performed on the same microcomputer in real time. To illustrate this, multicomponent analysis of kinetic transients is performed on simulated data and on the dissociation kinetics of the ethidium-DNA complex. PMID- 4025798 TI - A simple procedure for removing contaminating aldehydes and peroxides from aqueous solutions of polyethylene glycols and of nonionic detergents that are based on the polyoxyethylene linkage. AB - Commercial samples of polyethylene glycol as well as detergents incorporating the polyoxyethylene linkage may contain substantial concentrations of peroxides and aldehydes, as well as aldehyde precursors. Facile procedures for essentially eliminating either the first or all three of these contaminants from concentrated aqueous stock solutions are described. Under some conditions, the purified solutions can be stored at room temperature under aerobic conditions for time periods of weeks without significant decomposition. Possible antioxidants that might be used under other conditions to stabilize such solutions during long-term aerobic studies are considered. PMID- 4025799 TI - Purification of major basic glutathione transferase isoenzymes from rat liver by use of affinity chromatography and fast protein liquid chromatofocusing. AB - Seven major isoenzymes of glutathione transferase with isoelectric points ranging from pH 6.9 to 10 were isolated from rat liver cytosol. The purification procedure included affinity chromatography on immobilized S-hexylglutathione followed by high-performance liquid chromatofocusing. Characteristics, such as physical properties, reactions with antibodies, specific activities with various substrates, kinetic constants, and sensitivities to a set of inhibitors, are given for discrimination and identification of the different isoenzymes. The multiple forms of the enzyme correspond to glutathione transferases 1-1, 1-2, 2 2, 3-3, 3-4, and 4-4 in the recently introduced nomenclature [W.B. Jakoby et al. (1984) Biochem. Pharmacol. 33, 2539-2540]. A seventh form appears to be a heterodimeric protein composed of subunit 3 and an as yet unidentified subunit. PMID- 4025800 TI - Analysis of plasma cyanate as 2-nitro-5-thiocarbamylbenzoic acid by high performance liquid chromatography. AB - A method for the determination of cyanate concentration in blood plasma over the range 1 to 1000 microM is presented. Cyanate present in the dried residue of acetone-deproteinized plasma is converted to a chromophoric thiocarbamyl derivative by addition of pH 3.0-buffered thionitrobenzoic acid. The derivative is then analyzed by reversed-phase high-performance liquid chromatography with detection at 313 nm, near the absorption maximum. Carbamyl thionitrobenzoic acid peak height is quantified by comparison to a standard curve made by analysis of plasma samples to which known quantities of cyanate have been added. This technique is sensitive and linear with respect to cyanate concentration, and is faster than other reported methods; sample analysis and column regeneration are accomplished within 20 min. PMID- 4025801 TI - Purification of myosin light chains by high-performance liquid chromatography. AB - Three procedures for the purification of myosin light chains-1, -2, and -3 from avian fast white muscle fibers using high-performance liquid chromatography are described. Two involve the reverse-phase mode, the other, anion exchange. The procedures allow preparation of microgram to milligram amounts of the proteins and are suitable for the study of myosin light chains in small muscles and biopsy muscle samples. The elution order of light chain-1 and light chain-3, two proteins with extensive sequence homology, is discussed in terms of the unusual amino acid sequence and structure of the N-terminal peptide of light chain-1. PMID- 4025802 TI - Isolation of alpha 1-acid glycoprotein from human plasma using high-performance liquid chromatography. AB - A method for the rapid isolation of purified alpha 1-acid glycoprotein (AGP) from small volumes of human plasma using HPLC has been developed. The method involves preparation of the seromucoid fraction of plasma by sequential perchloric acid and phosphotungstic acid precipitations, followed by chromatography on an HPLC TSKG-3000 column. The yield was high (0.75 mg AGP/ml plasma) and the procedure takes less than 1 day. The method lends itself to easy automation and is particularly suitable for isotopic turnover studies requiring multiple plasma samples. PMID- 4025803 TI - The Cuisinart food processor efficiently disaggregates tissues. AB - The Cuisinart Model DLC-7 PRO food processor efficiently disaggregates plant and animal tissues resulting in time savings and often increased yields in the isolated material. PMID- 4025804 TI - A method for branched-chain amino acid aminotransferase activity in microgram and nanogram tissue samples. AB - A method for branched-chain amino acid aminotransferase is described which is based on running the reaction in the reverse of the usual direction with glutamate and alpha-ketoisocaproate as substrates. The alpha-ketoglutarate generated is reduced with glutamate dehydrogenase and NADH. For sensitivity in the nanomole range, the NAD+ generated is measured directly by converting to the highly fluorescent strong alkali product. For smaller samples, down to the 0.2- to 2-pmol range, the NAD+ is amplified by enzymatic cycling. PMID- 4025805 TI - Synthesis of methyl 2- and 4-pyridyl disulfide from 2- and 4-thiopyridone and methyl methanethiosulfonate. AB - In 1982, methyl 2-pyridyl disulfide was reported as a new reagent for the titration of thiol groups in peptides and proteins and for their temporary blocking with the thiomethyl group [T. Kimura et al. (1982) Anal. Biochem. 122, 274-282]. We have synthesized this compound (and its 4-pyridyl isomer) by a rapid and convenient procedure which is preferable to that in the original report. Our method involves the thiomethylation of the appropriate thiopyridone by methyl methanethiosulfonate. PMID- 4025806 TI - Fluorescent properties of histone-1-anilinonaphthalene 8-sulfonate complexes in the presence of denaturant agents: application to the rapid staining of histones in urea and Triton-urea-polyacrylamide gels. AB - In the present report it is shown that histone bands in urea-acetic acid or Triton-urea-acetic acid-polyacrylamide gels can be stained with the fluorescent dye 1-anilinonaphthalene 8-sulfonate and visualized by transillumination of the gel with an uv-light source. The 1-anilinonaphthalene 8-sulfonate staining method described here for urea and Triton-urea gels is rapid (it can be completed in 90 min) and allows the detection of less than 1 micrograms of histone per band. PMID- 4025807 TI - Bile acids. LXXII. High-performance liquid chromatographic analysis of bile acid coenzyme A derivatives. AB - The mobilities of coenzyme A and coenzyme A derivatives of cholate, chenodeoxycholate, deoxycholate, lithocholate, and their 5 alpha analogs were studied in reversed-phase high-performance liquid chromatography. With a C18 Radial-PAK A cartridge (10-micron particles) and a solvent mixture of 2 propanol/10 mM phosphate buffer (pH 7.0, 140:360), separation of the chenodeoxycholyl and deoxycholyl coenzyme A derivatives was not observed. An increase in ionic strength of the buffer to 50 mM afforded separation, which was markedly augmented with a C18 Radial-PAK A cartridge with 5-micron particles. Lowering the pH of the buffer to 5.5 did not materially change the separations regardless of the ionic strength. Quantitation was carried out to a lower level of 8.5 X 10(-12) mol. PMID- 4025808 TI - Dual-label high-performance liquid chromatographic assay for femtomole levels of benzo[a]pyrene metabolites. AB - A dual-label HPLC assay to measure femtomole quantities of ethyl acetate extractable [3H]benzo[a]pyrene metabolites was developed. 14C-labeled metabolites of benzo[a]pyrene formed by rat liver 9000g supernatant were used as both internal standards and chromatographic markers. The percentage deviation between assays was determined to be between 11 and 13% for 9,10-dihydro-9,10 dihydroxybenzo[a]pyrene, 7,8-dihydro-7,8-dihydroxybenzo[a]pyrene, benzo[a]pyrene 3,6-quinone, benzo[a]pyrene-1,6-quinone, and 9-hydroxybenzo[a]pyrene, 22% for 4,5 dihydro-4,5-dihydroxybenzo[a]pyrene, and less than 5% for 3 hydroxybenzo[a]pyrene. The detection limit of this assay was between 3 and 10 fmol per metabolite. The application of this technique to the metabolism of [3H]benzo[a]pyrene by microsomes of hamster and human oral cavity tissue is described. PMID- 4025809 TI - Microheterogeneity of the mammalian high-mobility group proteins 14 and 17 investigated by reverse-phase high-performance liquid chromatography. AB - Microheterogeneity within the HMG-14 and HMG-17 group of nonhistone chromatin proteins has been investigated using reverse-phase high-performance liquid chromatography (RP-HPLC) under conditions (acetonitrile elution with 0.1% trifluoroacetic acid as a weak ion-pairing agent) which separate proteins primarily on the basis of differences in their overall hydrophobicities. Ion-pair RP-HPLC proves to be a fast and efficient means for separating multiple subspecies of both the HMG-14 and the -17 proteins from both crude nuclear extracts and from ion-exchange column-purified protein samples obtained from different types of mammalian cell nuclei. In crude nuclear extracts at least two different HMG-14 protein species (one major and one minor) and three different HMG-17 species (two major and one minor) can be resolved by ion-pair RP-HPLC. The identity and purity of these HMG-14 and -17 protein species were assayed by polyacrylamide gel electrophoresis and amino acid analysis. The amount of HMG protein microheterogeneity observed by RP-HPLC equals or exceeds that found for these proteins by other analytical techniques and the results suggest that this heterogeneity may be due to factors other than protein size or overall net charge variability. PMID- 4025810 TI - Properties and applications of new monoclonal antibodies raised against calf DNA polymerase alpha. AB - A panel of 12 hybridoma cell lines secreting monoclonal antibodies against alpha polymerase were prepared by fusion of mouse myeloma cells and spleen cells of a rat immunized with homogeneous calf thymus alpha-polymerase. Hybridomas were selected and cloned on the basis of immunobinding to pure alpha-polymerase in solid phase radioimmunoassay. Antibodies secreted by these cells eventually were purified in milligram quantities from ascites fluids. These antibodies, all of the rat immunoglobulin M class, cross-reacted with alpha-polymerases from calf and monkey cells as revealed by immunobinding in radioimmunoassay and by immunoprecipitation of DNA polymerase activity. The antibodies were not capable of neutralizing the enzyme activity. With the methods described these antibodies may be used to immunoprecipitate alpha-polymerase from crude extracts of mammalian cells and to measure levels of the enzyme protein. PMID- 4025811 TI - Double-beam flying spot scanner for two-dimensional polyacrylamide gel electrophoresis. AB - The construction of a double-beam photometer in which the light source is a cathode ray oscilloscope is described. The light spot from the oscilloscope was focused and reduced in size at the gel plane to give a diameter of less than 0.15 mm and make it possible to scan over a 50 X 59-mm rectangle; using reduced spatial resolution (spot less than 0.2 mm) the area scanned becomes 70 X 90 mm. The light from the CRT was divided into two beams; one was directed through the transparent object to a photomultiplier and the other to a reference photomultiplier. The signals from these two detectors were converted to the logarithm of the ratio by a logging amplifier to give a direct measure of absorbance. Positioning of the spot, control of light intensity, and measurement of absorbance were carried out through an interface to a 16-bit computer. The relationship between measured and actual absorbance was linear over the range of absorbance 0 to 2, which could be raised to 1 to 3 by placing a neutral filter in the reference beam. The system generated an image containing 256 X 256 pixels in about 5 min, the scanning speed was determined by the persistence time of the P4 phosphor on the cathode ray tube, and faster scans can be made using A6 phosphor. PMID- 4025812 TI - Measurement of total protein in plant samples in the presence of tannins. AB - A method for measuring total protein in situ in plant samples has been developed using the determination of amino acids released by acid hydrolysis of dried plant material. Standard proteins and plant samples were hydrolyzed with 3% sulfuric acid at 100 degrees C for 24 h and the amino acids released were measured with ninhydrin. Unhydrolyzed plant extracts were also analyzed for free amino acids with ninhydrin. Total amino acid equivalents (protein plus free amino acids) of a diverse set of plant samples was significantly correlated with total protein as estimated by elemental analysis (N X 6.25). The Lowry method as modified by precipitation of proteins with trichloroacetic acid was found to be unsatisfactory for dried plant samples due to the incomplete extractability of proteins. Although some alkaloids caused increased absorbance with ninhydrin, interference with quantification of protein is likely to be minimal. Tannins interfered with the Lowry and Bradford methods but not the ninhydrin method. PMID- 4025813 TI - pH-dependent binding analysis, a new and rapid method for isoelectric point estimation. AB - Based upon the pH-dependent binding affinity of amphoteric molecules for an ion exchanger, and by taking advantage of batch procedures, a facile method was developed for estimating isoelectric points of these molecules. The new method allows pI measurements to be accomplished within 1 h. Moreover, any possible protein-ampholyte interaction or artifact formation, as may be introduced from the presence of carrier ampholytes when conventional focusing methods are employed, is eliminated by the method. In addition, because of the short processing time, isoelectric points of proteins can be measured at any desired temperature without much risk of protein denaturation. Seven proteins with well defined isoelectric points were examined by the method. The measured pI values were within a range of 0.2 pH unit or less of the reported values. The precision of pI measurements by the method can be even further improved with the employment of a narrower pH gradient. Since the isoelectric point is an important parameter which governs much of the art of separating proteins, the advent of a simple and rapid method for its measurement would be of use for selecting the proper strategy for protein isolation and purification. PMID- 4025814 TI - Extraction of dolichyl phosphate and its quantitation by straight-phase high performance liquid chromatography. AB - A procedure for the rapid quantitation of dolichyl phosphate by high-performance liquid chromatography on silica is described. The compound elutes as a single peak at 6 ml in excellent yield. The method employs isocratic elution and requires no column treatment between runs; the limit of sensitivity is in the nanogram range. Dolichyl-11-phosphate, which elutes at 7 ml, can be used as an internal standard, thereby eliminating the requirement for preparation of [3H]dolichyl phosphate. The procedure was used in development of a facile assay for free dolichyl phosphate in rat liver. For the assay of total dolichyl phosphate (free and chemically bound), it was found that when rat liver is first saponified and then extracted with ethyl ether, the amount of dolichyl phosphate present in the ether extract is significantly greater than the sum of the amounts found in extracts derived by treating the tissue first with chloroform/methanol (2/1) and then with chloroform/ethanol/water (10/10/3). Using these new procedures, the level of total dolichyl phosphate in rat liver was found to be 14.7 +/- 3.5 micrograms g-1 wet wt (n = 28). Levels in six other organs are also reported. PMID- 4025815 TI - A convenient assay for mephenytoin 4-hydroxylase activity of human liver microsomal cytochrome P-450. AB - A simple and rapid method for the determination of (S)-mephenytoin 4-hydroxylase activity by human liver microsomal cytochrome P-450 has been developed. [Methyl 14C] mephenytoin was synthesized by alkylation of S-nirvanol with 14CH3I and used as a substrate. After incubation of [methyl-14C]mephenytoin with human liver microsomes or a reconstituted monooxygenase system containing partially purified human liver cytochrome P-450, the 4-hydroxylated metabolite of mephenytoin was separated by thin-layer chromatography and quantified. The formation of the metabolite depended on the incubation time, substrate concentration, and cytochrome P-450 concentration and was found to be optimal at pH 7.4. The Km and Vmax rates obtained with a human liver microsomal preparation were 0.1 mM and 0.23 nmol 4-hydroxymephenytoin formed/min/nmol cytochrome P-450, respectively. The hydroxylation activity showed absolute requirements for cytochrome P-450, NADPH-cytochrome P-450 reductase, and NADPH in a reconstituted monooxygenase system. Activities varied from 5.6 to 156 pmol 4-hydroxymephenytoin formed/min/nmol cytochrome P-450 in 11 human liver microsomal preparations. The basic system utilized for the analysis of mephenytoin 4-hydroxylation can also be applied to the estimation of other enzyme activities in which phenol formation occurs. PMID- 4025816 TI - Separation of nucleosides and nucleotides by reversed-phase high-performance liquid chromatography with volatile buffers allowing sample recovery. AB - Reversed-phase high-performance liquid chromatography using a C18 column with volatile buffers as the eluant was applied to the separation of a number of nucleosides and nucleotides. Groups of seven nucleosides and five nucleoside monophosphates were separated isocratically employing 0.1 M trimethylammonium acetate and 2% acetonitrile at pH 7.0. Groups of seven nucleoside diphosphates and seven nucleoside triphosphates were separated with 0.1 M triethylammonium bicarbonate and 2% acetonitrile titrated to a pH of 7.1 with acetic acid. The techniques described give resolution and separations comparable to nonvolatile buffers. Moreover, the eluant trimethylammonium acetate or triethylammonium bicarbonate buffer can easily be removed in vacuo from the column effluent, making the technique useful for preparative separations of these compounds. The observed elution pattern of nucleoside phosphates suggests that "paired-ion" chromatography is involved in the separation. PMID- 4025817 TI - Nucleotide profiles of normal human blood cells determined by high-performance liquid chromatography. AB - An anion-exchange high-performance liquid chromatography method has been used to quantitate the intracellular purine and pyrimidine nucleotides in extracts of pure lymphocytes, monocytes, neutrophils, eosinophils, erythrocytes, and platelets isolated from the blood of healthy human donors. For accurate and reproducible measurements of the nucleotide profiles in different types of pure leukocytes, the cell suspensions have to be free of platelets and erythrocytes. Incubation of the purified leukocytes for 1 h at 0 degrees C did not alter the nucleotide concentrations but reduced the interdonor variation to 10%. Incubation of purified lymphocytes for 1 h at 37 degrees C caused considerable changes in the relative concentrations of the adenine, guanine, uracil, and cytosine nucleotides. During this incubation the cell viability, the cell number, and the ATP:ADP ratio decreased. Incubation of monocytes and granulocytes for 1 h at 37 degrees C caused considerable loss of cells and/or cell death. For erythrocytes and platelets reproducible nucleotide concentrations were obtained after extraction of freshly isolated cells. During storage of erythrocytes, both at 0 degrees C and at 37 degrees C, a decrease in the ATP:ADP ratio was detected. In all cell types the predominant nucleotides were purine nucleotides, especially adenosine triphosphate. The relative concentrations of the adenine, guanine, uracil, and cytosine nucleotides were very reproducible per cell type and appeared to be characteristic for each cell type. The total nucleotide content was nearly the same for all cell types except erythrocytes, when expressed per microgram of protein. The described methods for purification and storage of blood cells will be useful for comparison of blood cells from healthy donors with those of patients, for example, leukemia patients, in which deviations of the purine and pyrimidine metabolic enzymes have already been described. PMID- 4025818 TI - Protein quantitation of as low as 10-ng/ml concentrations by competitive binding to polystyrene latexes. AB - A protein quantitation method which offers protein detection as low as 10 ng protein/ml and accurate quantitation as low as 30-100 ng protein/ml, depending on the protein, has been designed. The assay, which is relatively quick and simple to perform, utilizes the strong, nonspecific adsorption of proteins onto polystyrene latexes. A competition is created between a marker enzyme and the analyte protein for a limited amount of latex surface area. Due to inactivation of the enzyme upon binding to a hydrophobic latex surface, measurement of enzyme activity allows determination of the bound/free enzyme ratio and thus the competing protein concentration. Considerations of sensitivity and simplicity are suggested to make this assay superior to others presently available. PMID- 4025819 TI - A radioisotope assay for 1-aminocyclopropane-1-carboxylic acid synthase: S adenosylhomocysteine analogs as inhibitors of the enzyme involved in plant senescence. AB - A simple and rapid radioisotopic assay for 1-aminocyclopropane-1-carboxylic acid (ACC) synthase was developed, an enzyme involved in the biosynthesis of the plant hormone ethylene. The assay utilizes an AG50W-X4(NH+4) column which separates S adenosyl-L-[carboxyl-14C]methionine (AdoMet) from the product [14C]ACC, since the latter is not bound to the resin while [14C]AdoMet is. As opposed to other assays, this procedure measures ACC directly and does not require further conversion to ethylene. When an enzyme preparation from ripe tomato fruits (Lycopersicon esculentum Mill). was assayed, an I50 of 2.5 +/- 0.8 microM for sinefungin and a Km of 27 +/- 2 microM for AdoMet were obtained; these values were in good agreement with previous determinations made with a gas chromatographic assay. When other nucleosides were tested as inhibitors, the following order of decreasing activity was found: sinefungin greater than S adenosylhomocysteine (AdoHcy) greater than AdoHcy sulfoxide greater than S-n butyladenosine greater than 3-deaza-adenosylhomocysteine greater than S isobutyladenosine greater than S-isobutyl-1-deazaadenosine. In contrast, S isobutyl-3-deazaadenosine, S-isobutyl-7-deazaadenosine, 3-deazaadenosine, and adenosine were not inhibitory. PMID- 4025820 TI - Method for extraction of proteins from green plant tissues for two-dimensional polyacrylamide gel electrophoresis. AB - A method has been developed for the extraction of proteins from green plant tissues to be used in two-dimensional polyacrylamide gel electrophoresis. Three purification steps were necessary to overcome the problems due to streaking, charge heterogeneity, and other artifacts: After it was ground in liquid nitrogen, the powdered material was stirred in the presence of insoluble polyvinylpyrrolidone for binding phenols, and sodium ascorbate for binding quinones; proteins were precipitated with ammonium sulfate, and the sample was dialyzed. Hundreds of proteins could be detected after Coomassie blue staining using 200 micrograms of proteins from apical buds of Sinapis alba L. PMID- 4025821 TI - Destruction of cyanogen bromide and inorganic cyanides. AB - Cyanogen bromide in water and seven organic solvents and sodium cyanide in water may safely and efficiently (greater than 99.7%) be destroyed using sodium hydroxide (1 M) solution and commercially available sodium or calcium hypochlorite. Details are given of an analytical procedure which can be used to check the final reaction mixture for the presence of residual cyanogen bromide or cyanide. PMID- 4025822 TI - An enzyme-linked immunosorbent assay to quantitate the elastin crosslink desmosine in tissue and urine samples. AB - An enzyme-linked immunosorbent assay method has been developed for the determination of desmosine. The method is based on an inhibition immunoassay (under nonequilibrium conditions) and uses rabbit antisera directed against a desmosine-bovine serum albumin conjugate and microtiter plates coated with desmosine-gelatin conjugate. The assay quantitates desmosine in the range 2.5-50 pmol in tissue and urine samples. Important applications of this rapid and sensitive assay are in studying elastin metabolism and in screening for monoclonal antibodies against desmosine. Methods are described for obtaining a constant level of substitution of desmosine per molecule of bovine serum albumin and for preparing a desmosine-gelatin coating antigen. Five different antibody preparations directed against desmosine exhibit 15-20% cross-reactivity toward pyridinoline (3-hydroxypyridinium), a nonreducible collagen crosslinking compound also present in urine and many tissue samples. PMID- 4025823 TI - Gold labeling of thrombin and ultrastructural studies of thrombin-gold conjugate binding by fibrin. AB - Monodispersed thrombin-gold (T-Au) conjugates were prepared by the absorption of a monolayer (3.8 nm thick) of human alpha-thrombin around individual monodispersed colloidal gold particles (16.5 +/- 1.8 nm). Like free molecular thrombin, T-Au conjugates can cause platelet aggregation, plasma clotting, and the release of fibrinopeptides A and B from fibrinogen. At the same thrombin concentration, T-Au conjugates have only one-tenth the fibrinogen-clotting activity of free thrombin and one-third the amidolytic activity of free thrombin. Hirudin can completely inhibit the fibrinogen-clotting activity of both T-Au conjugates and free thrombin, but can inhibit only half of the amidolytic activity of the conjugates. Diisopropyl fluorophosphonate can completely inhibit the fibrinogen-clotting activity and the amidolytic activity of both T-Au conjugates and free thrombin. T-Au conjugates were further characterized by studying the mechanism of their binding to fibrin and the location of the binding site on fibrin. The results of electron microscopic studies showed that T-Au conjugates, but not albumin-Au conjugates, are bound by fibrin. Increasing T-Au conjugate concentrations are associated with an increase in the number of T-Au conjugates binding to fibrin. At 0.1 microM thrombin, 73% of the T-Au conjugates are bound to branch points of the fibrin network with 27% of the T-Au conjugates present in the fibrin strands. At higher thrombin concentration (e.g., 0.5 microM) the percentage of T-Au conjugates bound to locations other than branch points increases to 62%.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4025824 TI - Release of a fluorescent probe as an indicator of lysosomal granule secretion by thrombin-stimulated human platelets. AB - Investigations in this laboratory have demonstrated that thrombin induces dose dependent changes in the transmembrane electrical potential of gel-filtered human platelets. This change is monitored with the fluorescent lipophilic cation, 3,3' dipropylthiodicarbocyanine (diS-C3-(5], whose rapid release from the platelet (maximal within 30 s) correlates with a rapid, dose-dependent influx of sodium, a depolarization, and an increase in the intracellular pH. There is also a later release of this probe, detectable only 60 s after activation by thrombin. It is shown that this latter probe release is also thrombin dose dependent, and correlates in time course and extent with the secretion of beta-glucuronidase from the platelet's lysosomal granules, implying that it corresponds to probe sequestered in these granules in the resting platelet. Such a conclusion is corroborated by the fact that both the thrombin-induced secondary release of diS C3-(5) and the secretion of the lysosomal enzyme, beta-glucuronidase, are inhibitable to the same extent by pretreatment of the probe-equilibrated platelets with valinomycin, a K+ ionophore, are partially inhibited to a comparable extent when thrombin is removed from the platelet membrane by an excess of hirudin within 15 s of activation, and are unaffected by amiloride, a Na+ blocking agent. We suggest therefore that some of the membrane potential probe diS-C3-(5) is accumulated by the platelet lysosomal granules and is secreted when the platelets are stimulated by the high doses of thrombin which induce lysosomal enzyme secretion. This secondary dye release is linearly proportional to, and can be used as a continuous and quantitative indicator of, the thrombin-induced lysosomal enzyme secretion by human platelets. PMID- 4025825 TI - Comparison of controlled pore glass and Kieselguhr-polydimethylacrylamide composite as supports for solid-phase synthesis of 23-residue oligodeoxyribonucleotides in milligram amounts. AB - Two 23-residue oligodeoxyribonucleotides, corresponding to both strands of a DNA duplex at the OR3 site of bacteriophage lambda, have been synthesized in good yields and in milligram quantities by a solid-phase phosphotriester method using two different supports, Kieselguhr-polydimethylacrylamide composite and controlled pore glass. Rapid purification was possible using high-performance liquid chromatography on radial compression ion-exchange columns. The results and utility of the two supports are compared. PMID- 4025826 TI - Elimination of the settling artifact in the nuclear magnetic resonance spectroscopy of living cells. AB - Nuclear magnetic resonance spectroscopy has become a powerful tool for metabolic investigations on living cell suspensions. However, unless mechanical means are used to maintain the cells in dispersion, settling occurs during the NMR experiment. Because high packed-cell volumes are generally used to produce maximum NMR signals, settling may be inapparent to the eye, leading to unrecognized artifactual changes in NMR spectra. Such artifacts include time dependent loss of signal intensity when the sample volume approximates the sensitive volume of the NMR probe, and time-dependent increase in signal intensity when the sample volume exceeds the sensitive volume. Through the addition of the polysaccharide arabinogalactan, increasing the buoyant density of the suspending medium to approach that of the cells, we have eliminated cell settling and improved the quality of 31P NMR spectra of human erythrocytes. PMID- 4025827 TI - A method for measuring both glutamine and glutamate levels and stable isotopic enrichments. AB - A method is described for measuring separately glutamine and glutamate levels and stable isotopic enrichment in plasma or whole blood samples by gas chromatography mass spectrometry (GCMS). Deuterated internal standards are used for the quantitation via reverse isotope dilution and are added to plasma samples immediately upon sample collection. The samples are then applied to miniature anion-exchange columns to separate glutamine and glutamate, and the separated fractions are derivatized for GCMS analysis. The internal standards serve not only to quantitate both amino acids by reverse isotope dilution, but also to correct for glutamine deamidation to glutamate during sample storage and handling. Glutamine and glutamate are quantitated from plasma with typical precisions of 1 and 16%, respectively. Plasma glutamine and glutamate amino-15N enrichments are determined with precisions of 2 and 12%, respectively. The precision of the glutamate measurements for whole blood is typically 6%, where the glutamate levels are higher. This method uses inexpensive columns, allows simultaneous processing of multiple samples, and requires minimal volumes of plasma (250 microliter). PMID- 4025828 TI - Flow injection amperometric determination of ascorbic acid and dopamine at a sessile mercury drop electrode without deoxygenation. PMID- 4025829 TI - Flow injection amperometric determination of nitroprusside at a glassy carbon electrode and at a sessile mercury drop electrode. PMID- 4025830 TI - Unusual electrochemical behaviour of a new phenothiazine. PMID- 4025831 TI - Comparison of tubular polymeric pH and ammonium ion electrodes as detectors in the automated determination of ammonia. PMID- 4025832 TI - Gas chromatographic-mass spectrometric determination of muramic acid content and pyrolysis profiles for a group of gram-positive and gram-negative bacteria. PMID- 4025833 TI - Spectrophotometric methods for the determination of o-dihydroxybenzene derivatives. PMID- 4025834 TI - A simple supersonic jet fluorimeter with a xenon arc lamp. PMID- 4025835 TI - Second Biennial National Atomic Spectroscopy Symposium. Leeds, UK, July 10-13, 1984. PMID- 4025836 TI - Determination of aluminium in biological materials by constant-temperature graphite furnace atomic-emission spectrometry. PMID- 4025837 TI - Determination of mercury in Chinese medicinal pills by cold vapour atomic absorption spectrometry. PMID- 4025838 TI - Controlled-dispersion flow analysis with atomic-absorption detection for the determination of clinically relevant elements. PMID- 4025839 TI - [Measurement of sperm motility by Laser-Doppler-spectroscopy in routine andrology lab tests]. AB - Sperm motility of 177 ejaculates from the andrology laboratory, University Clinic for Gynecology and Obstetrics, Graz/Austria, was evaluated in a comparative study. Motility was measured by Laser-Doppler-Spectroscopy (Lazymot) and by means of conventional microscopic estimations. For the first time results gained with Lazymot have been associated to different spermiogram diagnoses. In addition to measurements of percentages of total sperm motility, evaluations of mean sperm motility in micron/sec. have been performed. Correlation of results was good for both methods, besides the problem groups of ejaculates with sperm densities below ten millions of spermatozoa per milliliter. Motility characteristics of spermatozoa in an in vitro-Fertilization-Program have been subject to objective measurements with Lazymot for the first time. An enhancement of total motility (16%) and of mean spermatozoal velocity (36%) could be observed in the fertilization media after capacitation. Laser-Doppler-Spectroscopy represents a reliable and fast method for motility determinations in human ejaculate. It is suited for research purposes as well as for andrologic routine work. The operation of the Lazymot is considered to be unproblematic. PMID- 4025840 TI - The kinetic of acrosome reaction--an additional sperm parameter? AB - Spermatozoa of six men with normozoospermia, oligozoospermia and teratozoospermia were capacitated in vitro in modified Tyrode's medium und evaluated for acrosome reaction using the recently described triple-stain technique. The resulting kinetics illustrate the different capacitation behaviour and ability of spermatozoa to undergo acrosome reaction. The data were completed by the movement characteristics of spermatozoa during the incubation period. The kinetic of acrosome reaction seems to be an important functional sperm parameter that may be useful to discriminate between fertile and infertile spermatozoa. PMID- 4025842 TI - [Crossed sperm-penetration-meter test. Prognostic value in male subfertility]. AB - 57 infertile couples with "unknown" or "therapy resistant" infertility were investigated by the double crossed sperm-penetration-meter-test (SPM-test). The results of the SPM-test were compared with the results of the postcoital-tests, the duration of infertility, and the male and female diagnosis of infertility. Postcoital tests and SPM-tests showed only in 63% of cases corresponding results. The ability of the spermatozoa to penetrate cervical mucus was directly depending from the number of progressively motile spermatozoa per ml, and no connection could be found between the results of the SPM-test and the gynecological findings. The investigations showed that the primary diagnosis of infertility can be extended by the SPM-test respectively in many cases of so-called "unknown infertility" where a disturbed spermatozoa-mucus-interaction has to be postulated. PMID- 4025841 TI - Some preliminary observations on the liquefaction of human semen. AB - Liquefaction of human semen in vitro was studied by scanning electron microscopy, determinations of total protein, free amino acid and phosphate and by correlation analysis. During liquefaction of the coagulum, its fibers were transformed into globular bodies that fused to form the homogeneous liquefied semen. It was found that the parts of the ejaculate taking more time to liquefy possessed higher concentration of protein than those of the parts liquefied earlier, a relation also appeared to exist with the whole ejaculates. Release rate of phosphate during macroscopic lysis and free reducing sugar level of ejaculates demonstrated significant negative correlations with liquefaction time which could be shortened using reductants. PMID- 4025843 TI - Effect of glycerol and cryopreservation on oocyte penetration by human spermatozoa. AB - A poor penetration rate of glycerol-treated, cryopreserved human spermatozoa as compared to untreated fresh control, was observed in the zona-free hamster oocyte test. Similarly, glycerol treatment of freshly ejaculated spermatozoa depressed the penetration rate unless the culture medium also contained glycerol. Immediately after thawing, glycerol-treated, cryopreserved spermatozoa possessed adequate progressive motility, but their incubation in glycerol-free culture medium caused a severe reduction in motility. Even if the same number of progressively motile, cryopreserved, glycerol-treated spermatozoa as unfrozen spermatozoa were added to the eggs, a much lower penetration rate was obtained by the treated spermatozoa. It is concluded that spermatozoa develop a glycerol dependence and that removal of glycerol from the surrounding medium, as most likely occurs when spermatozoa pass through the cervix, reduces both the motility and the ability of spermatozoa to become capacitated and fuse with oocytes. Thus, glycerol is not an optimal cryopreservative agent. Further, the decreased oocyte penetration rate of glycerol-treated, cryopreserved spermatozoa is due to other factors besides the decrease in sperm motility. PMID- 4025844 TI - High-performance liquid chromatographic analysis of citric acid, inositol and fructose in boar and bull seminal plasma. AB - The efficiency of ultrafiltration and high-performance liquid chromatography (HPLC) in the routine analysis of dialysable sugar alcohols, organic acids and carbohydrates in boar and bull seminal plasma is evaluated. Permitting a simple and rapid separation of protein-free samples, ultrafiltration reduces the time of HPLC analysis by 40 minutes as compared to protein precipitation by means of methanol. Under optimal flow-conditions the separation of citric acid, inositol and fructose is achieved in 16 minutes. Moreover, the use of silicon-oil for separating seminal plasma within seconds is described. PMID- 4025845 TI - Classification of the semen of the male partners of infertile Nigerian couples. AB - Semen samples from 500 Nigerian male partners of infertile couples were classified according to their sperm counts and progressive motility. 74.15% of these men were normozoospermic while 16.19, 5.57 and 4.09% were azoospermic, necrozoospermic and asthenozoospermic, respectively. The degree of oligozoospermia was mild (35.88%), severe (23.22%) or very severe (40.90%). The classifications of two consecutive samples per patient collected two weeks apart were highly correlated. Results show that in over 70% of these infertile couples, infertility was due to a female factor, the absence of which therefore has to be established before semen analysis. Some socioeconomic factors in infertility were also implied. PMID- 4025846 TI - Gonadal response to psychosocial stress in male tree shrews (Tupaia belangeri) morphometry of testis, epididymis and prostate. AB - Male tree shrews (46 animals in all) were kept under distinct social conditions. Two kinds of controls were investigated: isolated animals as well as males out of female/male couples. Comparing these two groups only little isolation effect was observed. With the other individuals, initially isolated, dyads were formed which coexisted for 7 or 50 days. In a third group of dyads, after 50 days of coexistence social circumstances were aggravated for 5 more days by providing only half of the cage. All dyads established clear cut dominance relationship. Animals behaving dominantly developed no signs of gonadal regression rather that of stimulation concerning especially with the epididymis. In contrast, animals behaving as subordinates revealed profound regressive changes although differentiated with respect to any parameter, both morphological and conditional. In testis, chronical subordination (50 days, mainly 50 + 5 days) leads to a loss of organ weight, narrowing of seminiferous tubules and to enlarged spermatogonia nuclei. The case is similar in the epididymis: loss of organ weight, lowered epithelium and an enormously increased frequency of immature germ cells within tail segments. Whereas prostate weight drops continuously, striking histological regression occurs already after 7 days (extreme diminution of epithelial height and of epithelial cell nuclei). PMID- 4025847 TI - Alkylating agents and mouse spermatogenesis: effects of a single dose of cyclophosphamide. AB - Cyclophosphamide (CFA) is one of the alkylating agents which has now been used with some success in the treatment of human neoplasias and renal disease. To evaluate how this drug could affect the seminiferous epithelium, a single dose of CFA (200 mg/kg/weight) was given to twenty adult mice (strain A/SW). The effect of the drug was compared with a control group to which physiological saline solution was injected. Mice were sacrificed by cervical dislocation at four different time intervals after the drug administration in order to evaluate the action of the drug in different stages of spermatogenesis. The effect of the drug was appreciated as soon as four days after its administration. The initial damage to the epithelium was characterized by vacuolization of the Sertoli cells. Of all germ cells, primary spermatocytes showed the highest sensitivity to the drug. A high percent of teratozoospermia in the experimental group, when compared to the control group, was observed at all time intervals. The way CFA affects the morphology of mammalian spermatozoa and the usefulness of the animal model presented are discussed. PMID- 4025848 TI - Chromosomal analysis and health status of children conceived to men during or following dibromochloropropane-induced spermatogenic suppression. AB - Although the mutagenic effect of Dibromochloropropane (DBCP) on experimental mammal systems has been described, its possible effect on the human genome has not yet been investigated. The present study describes the results of chromosomal analysis and health evaluation of offspring conceived to families during and after paternal exposure to DBCP. Ten children conceived during or following severe exposure and four who were conceived prior to DBCP exposure were evaluated. The chromosomal constitution of peripheral lymphocytes was normal in all cases. The mode of delivery, birth weight, physical examination and growth pattern were normal. No congenital malformations were detected. One spontaneous abortion out of 23 pregnancies was recorded. These results suggest that paternal exposure to DBCP, severe enough to cause azoospermia or oligozoospermia did not alter the paternal sperm genome or the chromosomal constitution of offspring conceived during or after exposure. This is further supported by the excellent health and lack of malformations among the children, along with the low rate of spontaneous abortions in the families studied. PMID- 4025849 TI - Effect of intratesticular administration of serum on the physiological status of rat testis. AB - The effect of loss of integrity of seminiferous tubules on intracellular mechanisms in the testis of rats was studied after intratesticular administration of homologous serum. The increased weights of ventral prostate, seminal vesicles and increased activity of beta glucuronidase in kidney reflected an increased availability of testosterone to the target organs. The pulse labelling of 32P in the nucleic acid fraction of testis was significantly increased. The concentration of testicular DNA was increased while the ascorbic acid was slightly decreased. Activities of the lysosomal enzymes, acid phosphatase and beta glucuronidase increased. The involvement of lysosomal enzymes in the testicular function under altered condition was indicated. PMID- 4025850 TI - Fresh frozen plasma: too few indications--too much use. PMID- 4025851 TI - Morphine--caffeine analgesic interaction in rats. AB - The ability of caffeine to modify the effect of morphine on motor response to noxious stimulation was studied in 195 rat experiments. Motor reaction responses to noxious stimuli were studied in three series of experiments with three different techniques of mechanical tail stimulation. In each series of experiments, dose-response curves for morphine (probit analysis) were determined with and without the addition of caffeine (30 mg X kg-1). It was found that caffeine decreased morphine ED50 values in all three series of experiments, from 1.1 to 0.6 mg X kg-1 (P less than 0.002), from 3.2 to 2.5 mg X kg-1 (P less than 0.01), and from 13.2 to 6.2 mg X kg-1 (P less than 0.002). When caffeine was used alone in a dose of 30 mg X kg-1, there were no significant changes in motor reaction responses with any of the three methods applied for the assessment of morphine-caffeine combinations. These data indicate that caffeine potentiates the inhibitory effect of morphine on motor response to noxious stimulation in rats. It has been suggested that the effect of morphine on the motor response to somatic noxious stimulation results primarily from activation of inhibitory control systems concerned with this response. Caffeine may modulate the antinociceptive effect of morphine by stimulating one of these systems. PMID- 4025852 TI - Response differences of paretic and healthy extremities to pancuronium and neostigmine in hemiplegic patients. AB - The purpose of this study was to examine differences in train-of-four (TOF) ratios between paretic and healthy extremities after pancuronium and neostigmine administration in 31 patients with hemiparesis. The TOF ratios on the paretic side after pancuronium administration were greater than those on the healthy side in all patients. Patients were classified according to the size of the difference in the TOF ratio on both sides. In group 1, differences in TOF ratios were greater than 20%, and in group 2, they were less than 20%. Fifteen of 17 patients in group 1 had hemiparesis for over three weeks, and in group 2, 10 of 14 patients had hemiparesis for less than three weeks. Patients with flaccid hemiparesis were distributed equally in both groups, while all patients with spastic hemiparesis belonged to group 1. The difference in increase in TOF ratios after neostigmine was the same as the difference in decrease produced by pancuronium. PMID- 4025853 TI - Etomidate versus thiopental for induction of anesthesia. AB - Hemodynamic changes and side effects of anesthesia induction with etomidate or thiopental were evaluated in 83 ASA class I or II patients. Patients were randomly assigned to one of 12 groups according to pretreatment drug (fentanyl, 100 micrograms, or normal saline intravenously), induction agent (etomidate, 0.4 mg/kg, or thiopental, 4 mg/kg), and maintenance anesthetic technique (isoflurane oxygen, isoflurane-nitrous oxide-oxygen, or fentanyl-nitrous oxide-oxygen). The purpose of this experiment, of factorial design, was to evaluate the combined effects of two or more experimental variables used simultaneously and to observe interaction effects. There were significant increases in heart rate in all groups, especially after tracheal intubation. These increases were attenuated but not eliminated by fentanyl pretreatment. Systolic arterial blood pressure increased significantly after intubation and was not affected either by fentanyl pretreatment or by the induction agent. Patients in whom anesthesia was induced with etomidate had a greater incidence of pain on injection and myoclonus and a lesser incidence of apnea than patients in whom anesthesia was induced with thiopental. Fentanyl pretreatment significantly decreased the incidence of pain on injection and myoclonus, but it increased the incidence of apnea when anesthesia was induced with etomidate. The incidence of postoperative nausea and vomiting was similar after thiopental and etomidate and was unaffected by fentanyl pretreatment. (ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4025854 TI - Bupivacaine cardiovascular toxicity: comparison of treatment with bretylium and lidocaine. AB - Using anesthetized dogs, this study compared treatment with lidocaine or bretylium for bupivacaine-induced cardiovascular toxicity. Pentobarbital anesthetized and -ventilated dogs (n = 10) were given a bolus dose of bupivacaine, 4 mg/kg, and a constant infusion of 0.2 mg X kg-1 X min-1 to produce steady-state serum levels of 7.1 +/- 1.8 microgram/ml of bupivacaine. Using burst ventricular pacing, the ventricular tachycardia threshold was determined, along with hemodynamic and electrophysiologic parameters. The animals were then treated with bretylium, 20 mg/kg (n = 5), or lidocaine, 2 mg/kg, followed by a continuous infusion of lidocaine, 0.1 mg X kg-1 X min-1 (n = 5). Bupivacaine-induced alterations in cardiac output, stroke volume, heart rate, and systemic vascular resistance were corrected by bretylium but not lidocaine. Bupivacaine caused a significant lowering of the ventricular tachycardia threshold, which was consistently raised by bretylium, while lidocaine was either ineffective or caused a further lowering of the threshold. Bupivacaine caused a significant increase in the Q-TU interval and resulted in an undulating polymorphic ventricular tachycardia, similar to that seen in Torsades de Pointes. PMID- 4025855 TI - Differential spread of blockade of touch, cold, and pinprick during spinal anesthesia. AB - The differential levels of sensory blockade of pinprick, cold, and touch were monitored throughout the course of spinal anesthesia administered to 50 patients to determine variations in the degree of spread during onset, plateau, and regression, and to establish the effects of epinephrine and the effect of posture during injection. A significant difference was observed between the dermatomal level of sensory loss of touch and the dermatomal level of loss of either pinprick or cold during onset, at 5 min in patients given tetracaine with epinephrine, at time of maximum spread in patients given tetracaine with epinephrine or in the sitting position, and in all groups during regression. Loss of touch began later, never extended as far cephalad, and regressed sooner. The extent of this difference was greatest during regression, when the anesthetic was given to patients in the sitting position, after epinephrine. The level at which the sense of touch was lost seemed to mark the limits of the zone of solid spinal anesthesia; these limits could not be assessed effectively using pinprick. We propose that loss of touch sensation be used to assess whether anesthesia is adequate to avoid tourniquet pain. If there is loss of touch sensation above the L1 dermatome, it is unlikely that tourniquet pain will occur. PMID- 4025856 TI - Hemodynamic and plasma catecholamine responses to epinephrine-containing perianal lidocaine anesthesia. AB - Despite the frequent use of large volumes (30-40 ml) of epinephrine-containing local anesthetic solutions for ano-rectal surgery, little is known about the anesthetic-induced hemodynamic consequences. Therefore, we measured the heart rate, blood pressure, and plasma catecholamine (norepinephrine and epinephrine) responses to the perianal injection of 40 ml of 0.5% lidocaine alone (n = 8) or 0.5% lidocaine with 1:200,000 epinephrine (n = 10) in 18 healthy adults undergoing outpatient ano-rectal surgery. The mean +/- SEM plasma epinephrine concentration increased from a baseline of 42 +/- 7 pg/ml to a peak of 622 +/- 94 pg/ml 4 min after injection of epinephrine-containing anesthetic (P less than 0.001), whereas lidocaine alone increased the mean plasma value from 36 +/- 9 pg/ml (baseline) to only 69 +/- 16 pg/ml (not significantly different) at its peak. Despite the increases in plasma epinephrine levels in the group receiving epinephrine-containing anesthesia, no changes in blood pressure, heart rate, or plasma norepinephrine levels were observed. Given the advantages (including prolongation of the duration of anesthesia) of adding epinephrine to perianal local anesthetics, our data support its safe use in healthy adults. PMID- 4025857 TI - Paraplegia caused by spinal angioma--possible association with epidural analgesia. PMID- 4025858 TI - Balanced anesthesia: does it anesthetize? PMID- 4025859 TI - Myoclonus on recovery from etomidate. PMID- 4025860 TI - Anaphylactoid reaction to pancuronium. PMID- 4025861 TI - Hypokalemia and cardiac arrhythmias. PMID- 4025862 TI - Chronic hypokalemia and intraoperative dysrhythmias. AB - To investigate whether chronic hypokalemia increases the occurrence of dysrhythmias during anesthesia, the authors recorded the intraoperative electrocardiograms of normokalemic (K+ = 5.0 -3.5 mEq/l; N = 88) and chronically hypokalemic patients (K+ = 3.4 - 2.6 mEq/l; N = 62). In each patient, serum potassium was measured and a 12-lead ECG was analyzed prior to surgery. No patient received potassium perioperatively. Lead II was monitored continuously during anesthesia, either by a Holter monitor (N = 81) or by a trained observer (N = 69). A variety of general anesthetic techniques were utilized, without consideration for the potassium level. The hypokalemic population had a higher incidence of hypertensive and ASA Class III patients (P = 0.03). Analysis of variance revealed no significant difference in the incidence of other characteristics between the hypokalemic and normokalemic groups: age, hypoxemia, cardiac disease, preoperative dysrhythmias, digitalis therapy, surgical site, anesthetic agent, and intubation. The method of ECG monitoring did not affect the incidence of dysrhythmias recorded. Multivariate analysis revealed that the occurrence of intraoperative dysrhythmias correlated with the presence of preoperative dysrhythmias only. The authors conclude that chronic hypokalemia per se is not associated with a higher incidence of intraoperative dysrhythmias. PMID- 4025864 TI - Chemistry of halothane-enflurane mixtures applied to anesthesia. AB - The authors obtained boiling point-composition data and vapor pressure composition data for the halothane-enflurane system at 20 degrees C and 25 degrees C. This was used to demonstrate the existence of an azeotropic mixture of halothane and enflurane and to predict the output of an enflurane vaporizer contaminated with different amounts of halothane and a halothane vaporizer contaminated with different amounts of enflurane. The study was undertaken because the information allows a comprehensive description of the behavior of a contaminated vaporizer and the required data were not previously available. It was shown that an enflurane vaporizer contaminated with halothane delivers potentially dangerous mixtures of the two agents, whereas an enflurane contaminated halothane vaporizer does not pose a serious problem. It was concluded that when halothane and enflurane vaporizers are mounted in series, the halothane should be downstream. It is explained why the halothane-enflurane azeotrope is unlikely to be useful clinically. PMID- 4025863 TI - Bupivacaine toxicity in pregnant and nonpregnant ewes. AB - The relative central nervous system and cardiovascular toxicity of bupivacaine was compared in pregnant and nonpregnant ewes during continuous infusion of bupivacaine into the jugular vein at the rate of 0.5 mg X kg-1 X min-1. In all animals, identical symptoms of toxicity occurred in the following order: convulsions, hypotension, respiratory arrest, and circulatory collapse. The dose of bupivacaine required to produce central nervous system (CNS) toxicity in the pregnant ewe tended to be lower than in the nonpregnant animal, although the difference was not statistically significant (P less than 0.1). However, the mean dose of bupivacaine resulting in cardiovascular collapse was significantly lower in pregnant ewes (5.1 +/- 0.7 mg/kg) than in nonpregnant animals (8.9 +/- 0.9 mg/kg). Similarly, bupivacaine blood concentrations at the onset of respiratory arrest and circulatory collapse were lower in the pregnant group, being 5.2 +/- 0.7 micrograms/ml and 5.5 +/- 0.8 micrograms/ml, respectively, versus 7.5 +/- 1.0 microgram/ml and 8.0 +/- 0.9 micrograms/ml, respectively, in the nonpregnant group (P less than 0.05). The concentration of bupivacaine in the brain of pregnant ewes at the time of cardiovascular collapse was significantly lower (P less than 0.01) than in the nonpregnant group (7.5 +/- 1.5 vs. 16.3 +/- 1.7 micrograms/g). The myocardial tissue concentration of bupivacaine also tended to be lower in the pregnant group, although the differences were not statistically significant (P less than 0.1).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4025865 TI - Differential effect of nerve fiber structure on block by local anesthetic. AB - The incidence of conduction block by lidocaine 0.3 mmol/l (8.1 mg/dl) in several successive lengths of individual afferent axons of rabbit was compared. The conduction velocity of the axons was either "slow," "intermediate" (1.3-4 m/s), or "fast." The "intermediate" group showed a higher incidence of proximal acceleration of conduction (P less than 0.001) and a greater incidence of block (P less than 0.001) than the "slow" and "fast" fiber groups. The results were interpreted as indicating that the fibers of the "intermediate" group had an unmyelinated peripheral and a myelinated proximal length, with a junctional heminodal region that was the seat of the high sensitivity to block. The potential clinical significance of the observation is discussed in terms of the known distribution of heminodes in the peripheral nervous system. PMID- 4025866 TI - Cardiovascular and pharmacodynamic effects of high-dose fentanyl in newborn piglets. AB - To understand better the hemodynamic effects of fentanyl anesthesia on the developing newborn, the authors studied the changes in cardiac output and its four determinants (preload, afterload, heart rate, and contractility) and plasma fentanyl kinetics in newborn piglets following the administration of high-dose fentanyl with or without atropine premedication. Twenty-five healthy farm piglets were divided into four groups. Hemodynamic studies were conducted on five who received 50 micrograms/kg intravenous fentanyl, five controls who received only 0.01-0.03 mg/kg intravenous atropine, and nine who received both agents. Fentanyl pharmacokinetics were determined by radioimmunoassay in six additional piglets. Mean plasma fentanyl concentrations were 25.4, 12.7, and 7.9 ng/ml at 5, 15, and 30 min postbolus, respectively, with an elimination phase half-life of 35.8 min. In piglets given fentanyl alone, the maximum significant (P less than 0.05) hemodynamic changes from baseline occurred at 5 min: mean aortic pressure (MAP) +42%, cardiac output -42%, heart rate -36%, left ventricular end-diastolic pressure +81%, and total peripheral resistance index +93%. The latter four hemodynamic variables were highly correlated with the logarithm of the plasma fentanyl concentration (R2 greater than 0.96, P less than or equal to 0.05). In control animals given atropine alone, only MAP changed significantly (+12-14%) during the study. Contractile indices (echocardiographic shortening fraction and left ventricular peak dP/dT) did not change significantly in any group. Piglets given fentanyl-atropine had no significant hemodynamic change during the study other than a 7-15% increase in MAP. PMID- 4025868 TI - In vitro interaction between halothane and succinylcholine in human skeletal muscle: implications for malignant hyperthermia and masseter muscle rigidity. AB - This study examines in vitro the contractures induced by halothane and succinylcholine in skeletal muscle taken as biopsy specimens from 42 patients referred to the authors' laboratory for diagnosis of malignant hyperthermia (MH) susceptibility. In addition, possible differences between the response of preparations from these same patients with and without a history of masseter muscle rigidity following succinylcholine (SCh) administration were determined to investigate the in vitro relationship of masseter muscle rigidity to MH. Halothane 3%-induced contractures in preparations from MH susceptibles were similar, whether the group had a history of masseter muscle rigidity (1.15 +/- 0.18 g; n = 10) or not (1.02 +/- 0.21 g; n = 14). Halothane did not induce significant contractures in those diagnosed as normals. Succinylcholine alone did not elicit contractures from preparations derived from MH susceptibles or nonsusceptibles. Succinylcholine induced significant contractures in all preparations preexposed to halothane. Preparations from MH-negative patients with a history of masseter muscle rigidity were rendered sensitive to halothane (contractures of 1.17 +/- 0.30 g; n = 4) when SCh was present. In contrast, halothane added in the presence of SCh did not induce contractures to the same extent in preparations from MH-negative patients without a history of masseter muscle rigidity. This is the first reported in vitro method by which to examine the clinically troublesome interaction between SCh and halothane. This approach also may prove to be important in further investigations of the relationship between masseter muscle rigidity and MH. PMID- 4025867 TI - Different effects of thiopental in severe hypoxia, total ischemia, and low-flow ischemia in rat heart muscle. AB - The effect of thiopental (100 mg X 1(-1] during total ischemia, low-flow ischemia, and severe hypoxia with maintained flow was investigated in the isolated perfused rat heart. During total ischemia the rate of decline of tissue creatine phosphate and adenosine triphosphate was no different in thiopental treated and untreated hearts. The development of ultrastructural damage during total ischemia, the release of creatine kinase on reperfusion, and the exacerbation of ultrastructural damage after reperfusion were unaffected by thiopental. When thiopental was added to the perfusate during hypoxia and during low-flow ischemia at a normal pH(7.4), creatine kinase release during reoxygenation and during reperfusion was significantly less (P less than 0.005 and P less than 0.05, respectively) than in the untreated groups. After low-flow ischemia at a low pH (6.5), creatine kinase release was no different in thiopental-treated and untreated hearts. Thus, thiopental afforded protection of the myocardium in hypoxia and low-flow ischemia at pH 7.4 but not in total ischemia and low-flow ischemia at pH 6.5. The data are consistent with the hypothesis that during total ischemia and low-flow ischemia at pH 6.5, acidosis favors the entry of thiopental into the cell, causing inhibition of mitochondrial function and reduction of ATP production. During hypoxic perfusion and low-flow ischemia at pH 7.4, when the decrease in pH is less, the cardiodepressant effect of thiopental may offset any deleterious effect of the drug on intracellular organelles such as mitochondria. PMID- 4025869 TI - Perioperative hypothyroidism: an unusual postanesthetic diagnosis. PMID- 4025870 TI - Anesthetic considerations in cri du chat syndrome: a report of three cases. PMID- 4025871 TI - Pulse oximetry during one-lung ventilation. PMID- 4025873 TI - Airway obstruction after bilateral carotid endarterectomy. PMID- 4025872 TI - Placental transfer of ephedrine does not affect neonatal outcome. PMID- 4025874 TI - Infrarenal aortic cross-clamping and renal hemodynamics. PMID- 4025875 TI - Drug security for emergency surgical procedures. PMID- 4025876 TI - Succinylcholine and polyneuropathy. PMID- 4025877 TI - Pharmacokinetic basis for the dose-dependent decline in the neuromuscular blocking effect of gallamine. PMID- 4025878 TI - An unusual difficulty in fiberoptic intubation. PMID- 4025879 TI - Simplified vasoactive drug infusion. PMID- 4025880 TI - The relationship between sympathoadrenal activity and extrarenal potassium regulation. PMID- 4025881 TI - Antiarrhythmic effect of verapamil may be independent of calcium channel blockade. PMID- 4025882 TI - The diagnosis of "junctional rhythms" with halogenated anesthetics. PMID- 4025883 TI - Computerized anesthesia records may have drawbacks. PMID- 4025884 TI - Bilateral amaurosis following unilateral retrobulbar block. PMID- 4025885 TI - Cerebrovascular adaptation to prolonged halothane anesthesia is not related to cerebrospinal fluid pH. AB - The purpose of this study was to evaluate the time-dependent effects of steady state halothane anesthesia on cerebrovascular variables and their relationship to cerebrospinal fluid (CSF) pH. Eight mongrel dogs underwent a 7-h anesthetic, receiving halothane (1.0% end-tidal), O2 (50%), and balance N2. Cerebral blood flow (CBF) was measured by injection of radioactively labeled microspheres. CSF was sampled from the cisterna magna and cerebral venous blood from the superior sagittal sinus. Measurements were made at 2 h postinduction and hourly for 5 h thereafter. Total CBF at 2 h postinduction was 148 +/- 36 ml X 100 g-1 X min-1 and showed a significant decay over the subsequent 5 h to 70 +/- 3 ml X 100 g-1 X min-1. Regional variations were noted, those areas with highest initial flows showing both a greater relative and absolute reduction in flow. Cerebral vascular resistance increased significantly (39%), as did mean arterial pressure (15%). CSF pH values remained constant throughout the experiment. Arterial blood acid base physiology was also unchanged. Sagittal sinus PCO2 increased significantly from 43 +/- 4 to 49 +/- 3 mmHg while sagittal sinus pH decreased from 7.31 +/- 0.01 to 7.37 +/- 0.02, consistent with the normalization of CBF. Cerebral metabolic oxygen consumption did not change significantly. The authors conclude that time-dependent changes in cerebrovascular parameters under prolonged steady state halothane anesthesia are not due to changes in CSF pH and thus brain extracellular acid-base chemistry. PMID- 4025886 TI - The effect of high dose sodium thiopental on brain stem auditory and median nerve somatosensory evoked responses in humans. AB - Median nerve somatosensory evoked potentials (MnSSEPs), brain stem auditory evoked responses (BAERs), and the cortical electro-encephalogram (EEG) were recorded in six patients during a 62-min infusion of sodium thiopental (STP) at a rate of 1.25 mg X kg-1 X min-1 (total dose, 77.5 mg/kg). The EEG became isoelectric after 22 +/- 8 (SD) min of STP infusion. Dose-related changes in the latencies and amplitudes of various evoked response wave forms were observed. However, in no instance was any component of either the MnSSEP or the BAER rendered unobtainable by STP administration. For the MnSSEP, progressive increases in the central conduction time (5.33 +/- 0.41 ms preinduction vs. 7.46 +/- 1.2 ms at t = 60 min) and in the latency of the cortical primary specific complex were observed simultaneously with significant reductions in the amplitude of the latter (2.10 +/- 0.85 muV preinduction vs. 0.85 +/- 0.55 muV at t = 60 min). Changes in the latency and amplitude of the response recorded over the upper cervical spine (C2) were not statistically significant in this small population. For the BAER, progressive and significant increases in the latencies of Waves I, III, V (e.g., Wave V latency: 6.16 +/- 0.24 vs. 6.87 +/- 0.31 ms) and in the I-III, III-V, and the I-V interwave latencies were observed. The amplitudes of the BAER components were not significantly altered. The authors conclude that the administration of a dose of STP in excess of twice that required to produce EEG isoelectricity can be compatible with effective monitoring of MnSSEPs and BAERs. However, STP produces dose-related changes in both evoked response wave forms, which must be considered in the interpretation of responses elicited during STP anesthesia. PMID- 4025887 TI - Acute tolerance to fentanyl during anesthesia in dogs. AB - The effect of fentanyl on increases in heart rate and mean arterial pressure elicited by electric stimulation of a branch of the radial nerve was studied in anesthetized, paralyzed, and artificially ventilated dogs. In one group, a bolus of 100 micrograms/kg of fentanyl depressed the evoked changes in heart rate and arterial pressure by 82 and 75%, respectively, by 5 min, and recovery occurred within 90 min. A second group was given increasing bolus doses of fentanyl from 1.5 to 100 micrograms/kg every 20 min for 200 min. The doses and intervals were chosen to give a logarithmic increase in plasma concentration of fentanyl to include a final bolus dose of 100 micrograms/kg and were predicted by a two compartment pharmacokinetic model derived from data of the first group. In the second group, the bolus dose of 100 micrograms/kg after 5 min had no significant effect on evoked cardiovascular responses. Over the following 2 h, the evoked changes in heart rate and arterial pressure increased above those preceding the 100 micrograms/kg dose. An additional bolus dose of 100 micrograms/kg given 2 h after the first did not depress the evoked reflexes below the control values. It was concluded that tolerance to the effects of fentanyl can occur within 3 h and that for evoked responses to arterial pressure, rebound withdrawal effects can be seen within an additional 90 min. PMID- 4025888 TI - Local cerebral glucose utilization during nitrous oxide and pentobarbital anesthesia in rats. AB - Local cerebral glucose utilization was measured in rats during nitrous oxide and pentobarbital anesthesia, using the 2-[14C]-deoxyglucose method. During nitrous oxide anesthesia, 67%, marked heterogeneity of glucose utilization was observed. During pentobarbital anesthesia (30 mg/kg), glucose utilization decreased, the decrease being pronounced in the structures where glucose utilization was high during nitrous oxide anesthesia. During combined use of nitrous oxide and pentobarbital (30 mg/kg), with an electroencephalogram (EEG) consisting of 4-6 Hz wave super-imposed by 10-15 Hz wave, glucose utilization was higher in many brain structures, including the midbrain reticular formation, than that observed during pentobarbital (30 mg/kg) anesthesia alone. With pentobarbital, 125 mg/kg, the EEG became nearly flat and a dose-related decrease in glucose utilization was observed in the cerebral cortices and inferior colliculus but not observed in any other structures. During the combined use of nitrous oxide and pentobarbital (125 mg/kg), the EEG was nearly flat, and no statistically significant differences in glucose utilization were observed as compared with those during pentobarbital (125 mg/kg) anesthesia in any of the structures examined. The results suggest that nitrous oxide and pentobarbital affect local cerebral glucose metabolism differently and that nitrous oxide acts as cerebral metabolic stimulant in the presence of cortical function during pentobarbital anesthesia. PMID- 4025889 TI - Alterations in splenic lymphocyte subpopulations and increased mortality from sepsis following anesthesia in mice. AB - The authors evaluated the potential of a variety of anesthetics in mice to produce subsequent alterations in host defenses. Specific monoclonal antibodies and immunofluorescent microscopy were used to enumerate splenic helper/inducer: suppressor/cytotoxic lymphocyte ratios (HSR), and resistance to bacterial challenge was evaluated by a cecal ligation and puncture (CLP) model. Two hours of anesthesia with the intravenous agents ketamine and pentobarbital and with the inhalational agents isoflurane, enflurane, halothane, and halothane-nitrous oxide, were utilized. All anesthetics produced marked depression in the HSR, measured 24 h postanesthesia (P less than 0.05); with all agents, helper T-cell populations were decreased and suppressor populations increased. The HSR remained depressed 72 h postanesthetic, following both ketamine and halothane anesthesia (P less than 0.05). A dose-response curve was determined with enflurane; increasing the anesthetic time from 1 to 6 h resulted in progressively greater depression of the HSR 24 h later. Changes in lymphocyte subtypes of similar magnitude were found in mice after burn injury or hind limb crush injury and amputation, whereas simple laparotomy did not produce such changes. Serum corticosterone levels were not elevated 24 h post-anesthetic with enflurane, suggesting that the alterations were not nonspecific stress reactions. Resistance to sepsis was determined by measuring survival for 96 h after CLP. With CLP performed 24 h following 2 h anesthesia, mortality was increased from normal: control mortality 36.3%; ketamine 65.0% (P less than 0.023); isoflurane 69.5% (P less than 0.006); enflurane 84.2% (P less than 0.0002).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4025890 TI - Hepatic plasma flow during sodium nitroprusside-induced hypotension in humans. AB - Changes in hepatic plasma flow (HPF) during sodium nitroprusside (SNP) induced hypotension were studied in 14 patients undergoing intracranial aneurysm surgery under neurolept anesthesia. Patients were monitored with the use of a radial artery catheter and a thermistor-tipped Swan-Ganz catheter. Hypotension was induced with incremental increases in the rate of SNP infusion until a stable mean arterial pressure (MAP) 35-55 mmHg had been achieved. In one group (Group A) of 10 patients, indocyanine green (ICG) clearance was determined simultaneously with hemodynamic variables, before and during SNP hypotension. In a second group (Group B) of four patients, a catheter was inserted into a hepatic vein to determine the ICG hepatic extraction (HE) coefficient. In Group A, MAP decreased from 73 +/- 10 (SD) to 41 +/- 9 mmHg, while cardiac index (CI) decreased in six patients and increased in four patients. However, the mean value of CI did not change significantly. The mean value of ICG clearance was not significantly affected by SNP hypotension. Nevertheless, a positive linear correlation existed between individual variation in CI and ICG clearance (r = 0.96). On the other hand, no correlation was noted between the change in MAP and ICG clearance. In Group B patients, the ICG HE coefficient remained unchanged during SNP hypotension, suggesting that ICG clearance varies only according to the variation in HPF. In conclusion, this study demonstrated that HPF did not decrease, despite a range of 20-60% decrease in blood pressure when CI is maintained during SNP hypotension. PMID- 4025891 TI - Plasma concentrations of lidocaine and its principal metabolites during intermittent epidural anesthesia. AB - Plasma concentration-time courses of lidocaine and its principal metabolites (monoethylglycinexylidide, MEGX, and glycinexylidide, GX) were studied during intermittent epidural injections of lidocaine HCl in eight female patients (ASA status 1). The initial dose (320-400 mg without epinephrine) followed by top-up injections of about 60% of the mean initial dose every 35-55 min resulted in a plasma accumulation of lidocaine: the peak concentration increased from 2.30 +/- 0.46 (mean +/- SD) microgram/ml following the first injection and 3.34 +/- 0.76 microgram/ml after the second, to 4.11 +/- 0.72 microgram/ml following the third. The maximum concentrations of MEGX and GX were 0.66 +/- 0.22 and 0.28 +/- 0.08 microgram/ml, respectively. A pharmacokinetic model could successfully fit the entire plasma concentration-time profile of lidocaine during repeated epidural injections (r2 = 0.886 to 0.983). Such pharmacokinetic variables as elimination half-life (t1/2, 2.33 +/- 0.43 h), apparent volume of distribution divided by bioavailability (Vd/F, 2.51 +/- 0.61 l/kg), and clearance divided by bioavailability (Cl/F, 11.65 +/- 1.21 ml X kg-1 X min-1) obtained from the female patients were in reasonable agreement with those reported from healthy females receiving the intravenous lidocaine HCl. A computer-aided simulation generated from using the mean kinetic data in a 50-kg woman predicted that plasma lidocaine concentration would reach the postulated toxic range (approximately equal to 6 microgram/ml) after the fourth supplementary dose under a similar dosing scheme as performed in this study. In conclusion, an accumulation of lidocaine in plasma occurs during a usual intermittent epidural dosing.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4025892 TI - The use of a platelet nucleotide assay as a possible diagnostic test for malignant hyperthermia. AB - A bioassay, using high-performance liquid chromatography (HPLC) analysis of platelet adenosine nucleotides and hypoxanthine, was studied for its potential use as a test for MH susceptibility. A protocol for the assay was developed, based on the method outlined by Solomons and Masson. The HPLC procedure was a rapid, efficient, sensitive, and highly reproducible technique for measuring ATP, ADP, AMP, and hypoxanthine in platelets. Conditions of extraction and storage were critical for preventing degradation of the nucleotides. Extraction of nucleotides at icebath temperature was found necessary. Storage of platelet extract in PCA, even at -20 degrees C, showed loss of ATP and ADP; hence, neutralization with KOH was essential before storage. Contrary to the findings of Solomons et al., the present study demonstrated that neither ATP depletion nor per cent reduction in nucleotide ratios in platelets treated with halothane can be used as a definitive test for the diagnosis of MH susceptibility. The reason for this disagreement is unclear; however, differences in methods and altitude are implicated. It is possible that the platelet is not affected by malignant hyperthermia and thus cannot serve as a test system for the detection of the syndrome. PMID- 4025893 TI - Gas embolism produced by hydrogen peroxide irrigation of an anal fistula during anesthesia. PMID- 4025894 TI - Naloxone reversal of postoperative apnea in a premature infant. PMID- 4025895 TI - Intraoperative pacemaker complications. PMID- 4025896 TI - Subdural injection of local anesthetic: a complication of epidural anesthesia. PMID- 4025897 TI - Is there a risk of general anesthesia triggering SIDS? Possibly not! PMID- 4025898 TI - Another use for the plastic transparent dressing. PMID- 4025899 TI - Fixation of reinforced silicone tracheal tubes. PMID- 4025900 TI - Another potential failure in an oxygen delivery system. PMID- 4025901 TI - Possible pharmacologic trespass in pheochromocytoma patients. PMID- 4025902 TI - Use of petroleum jelly. PMID- 4025903 TI - Butorphanol and biliary spasm. PMID- 4025904 TI - Air embolism via a pulmonary artery catheter introducer. PMID- 4025905 TI - New endotracheal tube (Univent tube) for selective blockade of one lung. PMID- 4025906 TI - Medical alert--difficult intubation. PMID- 4025907 TI - Abstracts of scientific papers. 1985 annual meeting, American Society of Anesthesiologists. PMID- 4025908 TI - [Pharaoh's ant control by nest blockade]. PMID- 4025909 TI - [Tactics and strategy of malaria control]. AB - Tactics and strategy of malaria control. Both from the qualitative and quantitative point of view malaria can be regarded as one of the most serious medical problems of developing countries. In spite of decades of endeavours by the endemic countries and the World Health Organization using various tactics and strategies malaria prevalence and incidence could not be decreased essentially in tropical developing countries. The author analyses the reasons for this failure and gives realistic recommendations for lowering malaria morbidity and mortality taking into consideration the socio-economic conditions prevailing in the Third World. PMID- 4025910 TI - Coracidia agglutination reaction of pseudophyllid cestodes and its application in cestode studies. AB - The ability of cestode coracidia to agglutinate in homologous antiserum was established. The method of direct agglutination of coracidia (RDAC) in a culture of living larvae is described. The comparison of RDAC results in homologous and heterologous variants shows a dependence of the agglutination pattern on the degree of antiserum homology. By the example of RDAC of the cestodes Diphyllobothrium dentriticum and D. ditremum in polyvalent antisera and in antisera species-specific to D. dendriticum a possibility is shown of using RDAC in studies on species taxonomy of pseudophyllid cestodes. PMID- 4025911 TI - [Possibilities for controlling cockroaches in their hiding places]. AB - Possibilities for cockroach control in cracks and crevices. A simple pinnozzle is described which allows crack and crevice treatment. The construction of the needle attachment allows its employment in usual application equipments. This method requires higher qualification of the pest control operator and more time for application. There are less residues on surfaces in food areas and utenils. A hand duster is suitable for dust application. PMID- 4025912 TI - [Pathogenesis of Raynaud's phenomenon, disease and syndrome]. PMID- 4025913 TI - [Importance of the inferior mesenteric artery in the revascularization of the ischemic hypogastric region]. PMID- 4025914 TI - [Aortic surgery: analysis of 79 cases]. PMID- 4025915 TI - [Phlebomanometry in the study of post-phlebitic syndrome]. PMID- 4025916 TI - Hemodynamic factors changing blood flow velocity waveform and profile in normal human brachial artery. AB - We have investigated the influence of changes of perfusion pressure and local peripheral resistance on blood flow velocity waveform and profile in normal human peripheral arteries. Blood flow velocity and profile were recorded from the distal end of the left brachial artery in ten normal subjects by means of an ultrasonic device. The records were obtained in basal conditions and after blood pressure in the brachial artery and local peripheral vascular resistance were changed, separately or together, by progressive inflation of two arm cuffs, one encircling the proximal half of the left arm and the other the middle part of the left forearm. Both blood flow velocity waveform and profile were shown to be markedly modified by changes in perfusion pressure and local peripheral vascular resistance. Reduction of perfusion pressure decreased both forward and reverse peak velocities, but had the largest effect upon reverse velocity. The upslope and the downslope of the forward velocity wave were left unchanged. Increase in local peripheral vascular resistance markedly augmented reverse peak velocity, whether perfusion pressure was normal or reduced. Increased resistance only slightly influenced peak forward velocity. PMID- 4025917 TI - Problems and prospect of internal arterio-venous fistula for hemodialysis. AB - Vascular access for dialysis in patients with terminal renal failure has assumed increasing importance on surgical services as more and more facilities are developing to support such patients for longer period. Longevity of such vascular access is aimed for, meticulous care is needed in its creation. Direct arterio venous fistula is best method available, but in case of its failure, fistula formation using graft is useful alternative. Complications associated with vascular access still represent one of the most frequent and significant problems encountered in a hemodialysis center. Measures to overcome such problems are discussed. Historical background and literature are reviewed. Seven patients treated with maintenance hemodialysis are presented. One of them had severe haemorrhage from the fistula, an unusual complication of internal arterio-venous fistula. PMID- 4025918 TI - Photoplethysmography of the distal pulp in the assessment of the vasospastic hand. AB - A procedure for assessing the peripheral vasculature and a new technique for determining the characteristics of the a.c. (arterial) photoplethysmographic (PPG) waveform are described. Comparing 12 normal female volunteers and 12 female patients with Raynaud's phenomenon, PPG amplitude is as good as the results of a standard thermographic test in distinguishing between the groups. The limb arterial flow measured by strain gauge plethysmography (SPG) and the timing of features in the PPG waveform showed differences between the groups, which did not reach statistical significance. The rise time of the PPG waveform, however, was found to be correlated with age independently of vasospasticity. PMID- 4025920 TI - Diagnosis of vasospastic angina by analysis of heart rate response to exercise: effects of different levels of work load. AB - To examine alterations in control functions of the heart, which may account for the pathophysiologic conditions precipitating coronary arterial spasm, heart rate response to exercise in vasospastic angina was evaluated by using our previously developed method of frequency analysis. We also examined the effects of three different levels of work load on the heart rate response to treadmill exercise in 9 patients with vasospastic angina and 7 normal controls: stage 1 (2.5 Km/h, 10%), stage 3 (4.5 Km/h, 10%), and stage 5 (5.5 Km/h, 14%). The transfer function of heart rate control in vasospastic angina was characteristically different from that in normal controls: lower gain and more delayed phase angle of the system. Although this abnormality was observed in every test at 3 different levels of work load, the abnormality was more striking in tests at lower levels of work load: stage 1 or 3. The moderately light exercise test at stage 3 is most suitable as a test for detecting abnormal heart rate response to exercise in vasospastic angina because the exercise test at stage 1 had a poor S/N ratio. PMID- 4025919 TI - Subacute massive thromboembolic occlusion of a main pulmonary artery. Report of a case successfully treated by thrombolytic therapy and review of the literature. AB - Subacute massive thromboembolic occlusion of the left main pulmonary artery in a 52-year-old woman is described. This disease remains a rare entity with a much less dramatic presentation than acute massive pulmonary embolus. The presenting symptom was unexplained dyspnea. Physical signs and laboratory tests were nonspecific. The perfusion scan is the best screening test for this disorder. Antemortem diagnosis is established by pulmonary angiography. A literature review undertaken to ascertain the incidence of this entity as well as to recommend treatment of choice, be it medical or surgical therapy, was unrewarding. We decided to use thrombolytic therapy and found a marked improvement in the patient's symptoms and perfusion scan after 24 hours. Although thrombolytic therapy is commonly indicated for acute massive pulmonary embolism, we believe this mode of therapy should also be the initial treatment for subacute massive pulmonary thromboembolism. PMID- 4025921 TI - Huge left atrial thrombus and valve degeneration in a patient with a bioprosthetic, porcine, mitral valve. AB - A 43 year old man with a Hancock porcine bioprosthetic valve in the mitral position developed a huge thrombus filling the entire left atrium and chronic degeneration of the bioprosthetic mitral valve. The effective valve orifice was less than 2 mm. These severe findings leading to the patient's death remained undetected while he was alive. This case illustrates the great need for a serial phonoechocardiographic studies in all patients with prosthetic valves. PMID- 4025922 TI - The Osborn wave in hypothermia. AB - A patient is reported who presented with fatal hypothermia. The electrocardiographic changes of a sinus bradycardia, prolonged QT interval and Osborn waves were documented and correlated with body temperature. The possible genesis of these electrocardiographic changes is reviewed in this article. PMID- 4025923 TI - Focal vascular headaches with focal arterial disease. An ultrasonographic analysis. AB - The relationship between migraine and premature stroke and heart disease has been firmly established in the literature. The probable mechanism relates to release of vasoactive agents locally that produce intimal changes and if chronic may lead to permanent changes to the artery. We have attempted to identify individuals at risk for premature stroke utilizing the highly accurate B-mode real time carotid ultrasonogram. Sixteen patients demonstrated varying degrees of focal dilatation or plaque disease and 44% had abnormal Doppler flow studies. Since many of these patients were asymptomatic during the examination it is suggested that vascular changes may be more persistent than were previously suspected. These plaques, in the setting of increased platelet aggregability may be responsible for the augmented risk of stroke. Precise identification of these individuals can be easily accomplished with B-mode real time scanning (High resolution), and will allow for safe followup if specific dietary or drug interventions are contemplated. PMID- 4025924 TI - PISA--a new noninvasive method for early detection and quantification of ischemia in hypertensive patients. AB - Hypertension if untreated, is known to produce cardiac damage. Cardiac complications result from the effects of hypertension on the myocardium and/or to accelerated atherosclerotic changes in the coronary arteries. Presently available diagnostic tools are able to detect cardiac complications only when they are relatively at an advanced stage. Early detection of cardiac complications would have the advantage of early treatment, with potential for reversal. PISA (Phase Invariant Signature Algorithm) - a new noninvasive method has been shown by us to have high sensitivity and specificity for diagnosis of ischemic heart disease. This method was therefore used in 25 healthy individuals, 20 patients with documented ischemic heart disease and 50 hypertensive patients (duration 1-6 years) with no end-organ disease in order to determine if these patients have myocardial ischemia and/or infarction. These patients were on antihypertensive medication. Healthy individuals as expected, had phase-invariant PISA signature and low PISA index. All 20 patients with documented ischemic heart disease had phase variant signature and had high PISA index in two or more leads. The sensitivity of this method for detection of ischemic heart disease was found to be 100%. Twenty-nine of the 50 hypertensive patients were found to have phase variant (abnormal) PISA signatures and their PISA index was beyond the upper limit of normal PISA range (mean + 3S.D. of healthy individual). This study suggests that these 29 hypertensive patients possibly have ischemic heart disease. This PISA study indicates that 8 patients have anterior wall, 10 inferior wall, and 11 both anterior and inferior wall ischemia and/or infarction. These twenty-nine patients have varying degree of ischemia and/or infarction. PMID- 4025926 TI - Prognosis after myocardial infarction--prediction in ambulatory patients by use of the bedside Valsalva maneuver. AB - One hundred survivors of first myocardial infarction were studied prior to hospital discharge by 24 hour ambulatory electrocardiography as well as radionuclide ventriculography. The bedside Valsalva maneuver, with simple sphygmomanometric determination of arterial pressure response, was performed 6 weeks post infarction and patients were followed for a mean of 22 months. The arterial pressure response pattern provided a semiquantitative estimate of resting left ventricular systolic function when related to the radionuclide ejection fraction (SIN, 0.56 +/- 0.13; ABO, 0.43 +/- 0.18; SQW, 0.16 +/- 0.06) (P less than 0.02). Abnormal Valsalva responses (ABO and SQW) were found more commonly in patients with diminished left ventricular systolic function and high grade ventricular arrhythmias. The SQW response pattern was highly predictive of future sudden cardiac death. The bedside Valsalva maneuver, performed 2-4 weeks after hospital discharge, upon the ambulatory patient is a simple, safe, inexpensive and uniformly applicable method which may serve as the basis for a strategy with which to approach the post-infarction patient regarding risk stratification and further clinical management. PMID- 4025925 TI - Influence of the menstrual cycle on Raynaud's phenomenon and on cold tolerance in normal women. AB - Digital strain gauge plethysmography during a controlled cycle of hand warming and cooling was performed at weekly intervals through a single menstrual cycle in 10 normal women and 6 patients with idiopathic Raynaud's phenomenon (RP). Results were compared to those in 16 additional RP patients and 5 normal males. Maximum digital arterial flow at finger temperature 38 degrees C and reactive hyperemia following three minute arterial occlusion at 30 degrees C was comparable for all groups and did not vary with menstrual status. During cooling, normal women manifested plethysmographic loss of digital arterial flow at finger temperatures (18.1 degrees C +/- 7.9) intermediate between those of normal men (13.7 degrees C +/- 4.3, P less than 0.05) and RP patients (26.0 degrees C +/- 6.1, P less than 0.001). RP patients showed no change in cold tolerance in relation to menstrual status. However, normal women had variable responses to cooling and were found least cold tolerant at the time of menstruation with RP-like responses in all 10 cases although digital color changes were absent. These data support the hypothesis that RP in the premenopausal woman is physiologic and thus, in the majority of cases, not likely to evolve into a definable connective tissue disease. PMID- 4025927 TI - Femoral artery flow in deep vein thrombosis: hemodynamics of slow versus acute femoral vein occlusion. AB - There are many reports of reduced flow in the femoral artery following acute occlusion of the femoral vein. Poorer results might also be expected in arterial reconstructive surgery for obliterative vascular disease, in the event of deep vein thrombosis (DVT) of the limb. It is likely that patients develop DVT by a slow process that is totally different from experimental acute occlusion of the femoral vein, which leads to reduction of flow in the femoral artery. To test this hypothesis, a model with slow and gradual femoral vein occlusion was used. The results of this study showed that there was only 13.5% reduction in femoral artery flow during a four-hour gradual occlusion of the femoral vein. This excludes the possibility that in the presence of gradually occurring processes such as DVT, there is a hemodynamic basis for reduced flow through the femoral artery or through a bypass. PMID- 4025928 TI - Non invasive study of carotid arteries by echo-doppler and metabolic abnormalities in patients with dementia. AB - In order to evaluate the prevalence of common and/or internal carotid stenoses together with metabolic abnormalities in dementia nineteen patients were investigated. Dementia and differential diagnosis between Alzheimer type (DAT) and multi-infarctual (MID) dementia were performed on the basis of Computerized Tomography scan, behavioural anamnesis, neurological and neuropsychological examinations. Eight patients were diagnosed as MID and 11 as DAT. Noninvasive study of neck arteries was performed in supine position by a Duplex Scanner, able of detecting a wide range of stenosis, even when very mild. Arterial hypertension, hyperlipidemia, diabetes and high hematocrit level were present in both groups, although to a higher extent in MID (p 0.05). Results from Duplex Scanner demonstrate 12 vascular stenoses 16-49% and one between 50-99% (13/76), being vascular abnormalities equally distributed among DAT and MID patients. These data suggest that patients with metabolic abnormalities and arteriosclerosis can develop dementia not necessarily of vascular type. On the other hand, MID patients do not present higher number of stenosis as compared to DAT, indicating that vascular disease of carotid arteries is not prominent in the clinical context of dementia. PMID- 4025929 TI - Conservative treatment of lymphoedema of the limbs. AB - Management of Lymphoedema is extremely variable in the medical profession, ranging from aggressive diagnostic procedures, which may aggravate the disease (lymphography by oily contrast mediums) in combination with therapeutic nihilism to precipitous operations. Scattered between these two contraversial extreme positions are quite a number of various conservative methods - some of which being in conflict with the anatomy and physiology of the lymph vascular system and the pathology of Lymphoedema. Lymphoedema, if left untreated, or is treated inadequately, may lead to invalidity and to death if Stewart-Treves Syndrome develops. Unnecessary surgery may have disastrous consequences. The paper describes how Lymphoedema can be treated with success, free of any side effects, by complex physiotherapy. PMID- 4025930 TI - Buerger's disease in women. A case report with critical approach to the literature. AB - The Authors describe a case of arteritis of the lower limbs in a woman, in which the clinico-angiographical features were suggestive for Buerger's disease, and this was confirmed by histological examination of the left posterior tibial artery. A bilateral lumbar sympathectomy was effective at least in slowing the course of the disease. PMID- 4025931 TI - A case of aortitis syndrome with severe coarctation of the aorta. AB - A 17 year old female with aortitis syndrome was reported. The blood pressure of upper extremities was 204/88 mmHg which was higher than that of lower extremities (88/mmHg). Chest X ray showed marked rib notchings at the lower border of the right 7th and 8th rib and left 8th ribs. Stenosis of the thoracic aorta was observed at the upper border of the 9th rib and the lower border of the 10th rib with marked development of collateral circulation. After 6 months treatment with steroids, inflammation signs were improved and thickness of the aorta was decreased which was detected by computed tomography. However, blood pressure was not decreased by the combined antihypertensive treatment. PMID- 4025932 TI - The importance of the lymphatic system. PMID- 4025933 TI - Quantitation of pulmonary emboli with pulmonary cineangiography: preliminary report. AB - Pulmonary angiography is considered the definite method of diagnosing pulmonary emboli. It is hypothesized that pulmonary cineangiography is superior to conventional pulmonary angiography for quantitation of pulmonary emboli. The present study was undertaken to test the hypothesis. Six patients with an age range from 27 to 70 years with documented pulmonary emboli by pulmonary angiogram, had pulmonary cineangiograms. Pulmonary angiogram defined pulmonary emboli in nine major vessels in the six patients; while, pulmonary cineangiogram revealed another 10 major vessels with pulmonary emboli, which were either not detected or considered equivocal by the conventional pulmonary angiography. The pulmonary embolic score as an index of the extent of pulmonary emboli was 24 (mean 4 +/- 2.52 1SD) by the conventional pulmonary angiography, while the score was 60 (mean 10 +/- 3.22 1SD) by the pulmonary cineangiography, P less than 0.2. Thus, in cases with pulmonary emboli, pulmonary cineangiogram is superior to conventional pulmonary angiogram for the quantitation of pulmonary emboli. PMID- 4025934 TI - The "blue toe" syndrome with renal atheroembolism and failure. AB - The occurrence of atheromatous embolization following cardiac catheterization and coronary artery bypass surgery is described. It was manifested initially by bluish discolored toes inciting suspicion of vasospasm and then by progressive renal failure. The diagnosis was confirmed by renal biopsy. The syndrome of multiple atheromatous or cholesterol emboli is probably more common than previously reported because of its masquerade of other illnesses and failure of consideration of diagnosis. PMID- 4025935 TI - Lidoflazine and propranolol combination treatment in chronic stable angina. AB - The short-term (1 month) and long-term (6 months) safety of combination lidoflazine-propranolol therapy was investigated in an open trial of 15 patients with stable angina of effort. The possible advantages of adding lidoflazine (titrated to 360 mg daily) to patients having a therapeutic response to propranolol (80-400 mg daily) was also evaluated. Effects on non-invasive indexes of left ventricular function (echocardiography, systolic time intervals, radionuclide ventriculography) and exercise tolerance (treadmill exercise testing) were determined. There was no change in mean resting heart rate with the combination therapy, although one patient developed sinus bradycardia at a rate of 44 and had to have his propranolol dose reduced. Electrocardiographic analysis showed significant prolongation of the QTc intervals on lidoflazine-propranolol therapy compared to propranolol alone, with 3 patients having QTc interval prolongation to above .53 seconds, but there was no evidence of increased arrhythmogenesis with the combination therapy compared to propranolol alone. Left ventricular end-diastolic volume index tended to rise with combination therapy. However, lidoflazine-propranolol therapy did not produce any significant effects on resting ejection fraction determined by M-mode echocardiography or by radionuclide ventriculography. Radionuclide ventriculography determined peak exercise ejection fractions were also not significantly changed with combination therapy compared to propranolol alone. There were only small, insignificant improvements in exercise tolerance with the lidoflazine-propranolol combination treatment compared to propranolol alone. It is concluded that lidoflazine propranolol combination therapy is generally safe but has the potential of causing serious adverse effects in certain patients, i.e. those with sick sinus disease, prolonged QTc intervals, and severe baseline left ventricular dysfunction, and that caution must be exercised in its use. Furthermore, it would appear that combination therapy provides only slight, if any, improvements in exercise tolerance in patients with chronic stable angina having a therapeutic response to oral propranolol. PMID- 4025936 TI - What is the optimum A-V interval in D.D.D. pacing? AB - One of the programmable parameters in recent pacemakers is atrio-ventricular interval. To find out the optimum A-V interval studies were done in 14 patients. Multigated radionuclide scans were used to measure the left ventricular function, at a resting heart rate of 70/minute. Seven patients had poor left ventricles (ejection fraction less than 50%). Left ventricular ejection fraction, relative cardiac output and end diastolic counts were highest at 250 M. Sec. interval compared to 150. Ejection rates and end systolic counts were not related to A-V interval. Relative cardiac output was 27% higher in poor ventricles at 250 delay than 150. This observation was not significant in normal hearts. Optimum P-R interval is 250 M. Sec. for maximum left ventricular function. PMID- 4025937 TI - Biochemical analysis of dermal connective tissue in subjects affected by primary uncomplicated varicose veins. AB - Biochemical analysis of dermal connective tissue was carried out in 14 subjects affected by primary uncomplicated varicose veins and 14 controls. Skin samples were taken, according to fixed criteria, from operation pieces of total mastectomy for breast cancer. The results suggest that the dermal tissue in these subjects is just thinner than that of controls, confirming previous similar clinical findings. The elective reduction of the collagen content observed, unassociated with changes of other components of the dermal connective tissue, brings evidence for a systemic biochemical defect of the extracellular matrix i.e. a collagen defect affecting the entire body structure and not only the varicose or pre-varicose veins of the lower limbs. PMID- 4025938 TI - Complications of vascular access devices for hemodialysis. AB - Hemodialysis is essential in the management of end stage renal disease patients. Forty-eight contrast examinations of hemodialysis vascular access devices were reviewed. Venous fistulography is the method of choice for the evaluation of these devices. Only 12 patients in this series required arteriography and 6 of them had a lower extremity access device. The most common complications included venous stenoses, venous or graft aneurysms, pseudoaneurysms and venous or graft thrombosis. Pseudointimal proliferation resulting in graft stenosis was also observed. PMID- 4025940 TI - Mortality and morbidity in patients with intermittent claudication in relation to the location of the occlusive atherosclerosis in the leg. AB - Mortality and morbidity from cerebrovascular and coronary arterial disease over a period of six years were studied in 224 non-diabetic patients with intermittent claudication. Patients with multiple arterial stenoses in the leg had a lower six year survival than patients with single stenoses (55% versus 77%), with a higher mortality from cardiac deaths. These differences were still significant after adjustment for differences in clinical characteristics at the initial examination. This might indicate that patients with multiple arterial stenoses in the legs have a more widespread and more progressive atherosclerotic disease. PMID- 4025941 TI - Lightning-induced myocardial injury. A case report with management. AB - A young patient of lightning induced myocardial injury with chest pain is described. Electro-cardiogram mimicked true myocardial infarction (due to coronary artery disease). Practical aspects of case management is discussed. Use of short course of steroid helped in early recovery. PMID- 4025942 TI - The noninvasive laboratory--history and future of thermography. AB - A brief history of thermography and recent developments in instrumentation have been reviewed. Important applications are related to thrombophlebitis, the cerebral circulation, peripheral arterial abnormalities and medical-legal situations. PMID- 4025939 TI - The prevention of Ca2+ overload in vascular smooth muscle by flunarizine as detected by Laser Microprobe Mass Analysis (LAMMA). AB - In vitro exposure of depolarized caudal artery preparations of the rat to a high calcium concentration resulted in a strong contraction of the smooth muscle cells. This muscle contraction was suppressed by flunarizine. It was shown cytochemically, using the combined oxalate-pyroantimonate method for the localization of calcium, that a considerable amount of electron-dense precipitate was seen over the depolarized muscle cells after incubation in a calcium containing medium. On the other hand this precipitate was not present on the smooth muscle cells when flunarizine was added to this incubation medium. The reaction product was only present in the extracellular space. These results were controlled by Laser Microprobe Mass Analysis. By evaporating and ionizing small parts of the smooth muscle cells (+/- 1 micron), it was confirmed that the cytochemical method indeed demonstrated calcium, with negligible interference of other cations. PMID- 4025943 TI - Delayed fatal pulmonary hemorrhage complicating use of a balloon flotation catheter. AB - A case of delayed fatal pulmonary hemorrhage caused by a balloon flotation catheter is described. The catheter was inserted preoperatively. The patient died on the 14th postoperative day from massive hemorrhage in the right pleural space after 12 days without any clinical symptoms. Pulmonary artery rupture is documented by the autopsy findings. PMID- 4025944 TI - Laboratory control of continuous intravenous heparin therapy with Howel time and activated partial thromboplastin time. A prospective, randomized and blind study. AB - Although heparin has been used extensively to treat Deep Venous Thrombosis (DVT) and arterial ischemia (AI), controversy still exists regarding optimal dosage and the need for monitoring. Different authors have employed various test with variable results. Others, however, persist in giving heparin without laboratory control. This study was made in order to compare, in a prospective, randomized and blind manner, two coagulation tests, namely: Howel Time (HT) and Activated Partial Thromboplastin Time (APTT), in controlling the dose of heparin given by continuous intravenous infusion in DVT and AI. Our results show no significant difference in complications and failures of the therapy with either test, although significantly higher doses of heparin were needed to maintain APTT within therapeutic range than those needed to keep HT within a similar range. PMID- 4025945 TI - Haemorheological parameters in hypertensive Nigerians with and without sickle cell trait. AB - Haemorheological parameters including whole blood (WBF) and erythrocyte filterability (EF), haematocrit (H'ct), haemoglobin levels (Hb) and plasma fibrinogen concentration (PFC) were measured in 61 adult Nigerians with uncomplicated essential hypertension during the course of their routine anti hypertensive treatment. Results from these patients were compared to those of 39 age and sex-matched normotensive controls. Sixteen (26.2%) of the hypertensive patients and 6 (15.4%) of the controls had the sickle-cell trait (HbAS); the rest were normal homozygotes (HbAA). Although there were no significant difference between WBF in the HbAA-hypertensive and control groups, the former had a significantly lower EF than the latter (p less than 0.025). Both WBF and EF were highly significantly decreased in the HbAS-hypertensives (p less than 0.001). Significant differences in H'ct and Hb levels between HbAA-hypertensives and controls were attributed to sex rather than to hypertension per se. Plasma fibrinogen concentration values were consistently and significantly elevated in all hypertensives irrespective of sex or haemoglobin genotype. In contrast to the HbAA-hypertensives, all 16 HbAS-hypertensives had a persistently raised diastolic blood pressure above 90 mm Hg, suggesting that these patients are either resistant or are less responsive to conventional anti-hypertensive therapy. A more extensive follow-up study is in progress to assess the possible relationship of these parameters and blood pressure, particularly in hypertensive individuals with sickle-cell trait (HbAS). PMID- 4025946 TI - Gangrene of the foot: a complication of phlebography. AB - One believes there is a necessity to bring to widespread attention a most serious complication of what is often considered a mundane radiological examination - lower extremity contrast venography. So mundane is it considered in fact, that outside of resident teaching programs, an informal telephone survey of 15 hospitals from 240 beds to 780 beds revealed that a number of injections and examinations: (a) were conducted entirely by technologists without any pretense of radiologist supervision; (b) that the radiologist "supervised" the injection (i.e. was in the "immediate vicinity") or; (c) injection was preferentially done by the radiologist, but no reason was seen why a skilled non-physician could not conduct the examination. PMID- 4025947 TI - Detection of shunt flow in total anomalous pulmonary venous connection using 2D Doppler echocardiography. AB - Two-D-Doppler echocardiography was used to diagnose two cases of total anomalous pulmonary venous connection (TAPVC). The first case presented the supracardiac type, the second the infracardiac type. Blood flow imagings produced by 2D Doppler echocardiography revealed shunt flow in the common pulmonary veins (CPV) and the vertical, innominate, and portal veins. The shunt flow in the vertical vein was laminar, though the shunt flow in the inflow tract of the right atrium was turbulent. Two dimensional Doppler echocardiography is very useful in the detection shunt flow in TAPVC. PMID- 4025948 TI - Cardiovascular manifestations in systemic lupus erythematosus. Prospective study of 100 patients. AB - One hundred consecutive female patients with active systemic lupus erythematosus (SLE) were studied from the cardiovascular point of view by means of non invasive methods. Seventy percent of the cases presented some type of cardiovascular anomaly. Seventy four percent of the resting electrocardiograms were abnormal as well as 72% of the M mode echocardiograms and 55% of the cardiac X ray series. The most frequent observed complications were: pericarditis and or pericardial effusion (39%), arterial hypertension (22%), ischemic heart disease (16%), myocarditis (14%), congestive heart failure (10%), pulmonary hypertension (9%), valvular heart disease (9%), pleural effusion (7%) and cerebro vascular accident (3%). We analyzed each one of these complications and found of special interest the high incidence of ischemic heart disease which is more frequent than has been hitherto reported. Ischemic heart disease was observed in two types of patients: a) Those with long term steroid therapy. In these, the mechanism seems to be an atherosclerotic disease probably induced by the chronic use of steroids. The management of these cases do not differ from other types of coronary heart disease due to atherosclerosis. b) Those with frank episodes of vasculitis in whom the basic mechanism is an inflammatory process of the coronary arteries and its treatment is fundamentally that of the vasculitis. We consider necessary to study routinely all patients with SLE through non invasive cardiological methods. PMID- 4025949 TI - Hydrodynamic flow in U-shaped and coiled glass loops simulating carotid arterial configurations. AB - The dye injection technique was used to study flow patterns in ten U-bends and two helical coils. These models were manufactured of glass and designed to simulate abnormal arterial configurations in man. In each model flow disturbances were observed below the critical Reynolds number of 2000 for flow in a straight tube with one reading as low as 250. The disturbances in the flow were sensitive to external disturbances. Their periodicity was relatively regular but the frequency increased with augmentation of flow rates and some irregularity was apparent. The results indicate that they could have applicability to the human vascular system. PMID- 4025950 TI - An S.E.M. corrosion cast study on pericyte localization and role in microcirculation of skeletal muscle. AB - The authors used the microcorrosion cast technique to study the localization and the role of pericytes in the microcirculation of skeletal muscle. Both fast twitch muscles, the tibialis anterior and the pectineus muscles, and a slow twitch one, the soleus muscle, were studied, because of morphological differences of their capillary networks. The observation of peculiar imprints on the surface of vascular casts, strategically sited in the microvascular bed, were related to the presence of pericytes apposed to the endothelial lining. The role of pericytes in equalizing the local blood flow to metabolic needs and in maintaining capillary blood flow despite pinching of vessels is discussed. PMID- 4025951 TI - Embolization of a sciatic artery aneurysm an alternative to surgery: a case report. AB - An elderly woman was admitted with a 2-day history of pain, numbness and coolness of the left lower limb. The left foot on examination was cool and blue with no palpable pulse nor motor or sensory function. An arteriogram demonstrated a dilated persistent sciatic artery. The superficial femoral artery was hypoplastic and there was poor visualization of the distal circulation. At surgery an occluded popliteal artery was found. Attempts to open the occluded artery were unsuccessful and a left fibulectomy and fasciotomy was performed and the patient started on intravenous heparin. The patient's condition deteriorated and on the 4th hospital day an above-knee amputation was undertaken. The patient made an uneventful recovery and was subsequently discharged. At follow-up a month later the aneurysm was still patent and strongly pulsatile. She was readmitted to the hospital and the aneurysm was successfully embolized. PMID- 4025952 TI - Unusual electrocardiographic abnormality in leptospirosis: case reports. AB - Unusual ECG changes of marked ST segment elevation in leads V1 to V3 are reported in four cases of severe icteric leptospirosis for the first time. These changes normalized rapidly with initiation of therapy and recovery in three patients. One patient died within hours of admission. The causes for the changes are not clear. PMID- 4025953 TI - Status asthmaticus with acute respiratory failure. PMID- 4025954 TI - The Bela Schick lecture for 1984. Deciding the future for the practice of allergy and immunology. PMID- 4025955 TI - Response to bronchodilator in the asthmatic: an alternative method of analysis. PMID- 4025956 TI - Food allergy and adult migraine: double-blind and mediator confirmation of an allergic etiology. AB - Foods as a cause for migraine attacks were evaluated in 43 adults with recurrent migraine. Skin testing, elimination diets, double-blind challenges, and measurements of plasma histamine were performed. Thirteen subjects experienced 66% or greater reduction in headache frequency during a diet trial. Six subjects became headache free. Eleven of 16 skin test-positive patients responded to diet manipulation, while only two of 27 skin test-negatives did (P less than .005). Seven subjects agreed to double-blind challenges. In five of seven, at least one food provoked migraine. Placebo challenges did not provoke migraine. In three subjects, plasma histamine rose during migraine provoking challenges. The relationship between food ingestion and migraine is based in part on allergic mechanism. Tests for IgE-specific food allergy appear helpful in selecting patients likely to benefit from diet therapy. PMID- 4025957 TI - Influence of hyposensitization with Dermatophagoides pteronyssinus extract on clinical score, total and specific IgE levels, and skin test in asthmatic patients. AB - To evaluate the effects of immunotherapy on clinical response, on IgE serum level, on radioallergosorbent test (RAST), and on skin tests, a prospective study was performed by a follow-up of 73 asthmatic patients allergic for house dust during hyposensitization with Dermatophagoides pteronyssinus extract. No relationship could be found between the evolution of clinical score, skin tests and RAST, but 91% of the patients with a decreasing IgE serum level had satisfactory clinical results. Serial determinations of serum IgE levels during hyposensitization showed two patterns of evolution with a favourable prognostic value: a continuously decreasing serum IgE or a primary increase followed by a late decrease. PMID- 4025958 TI - Occupational respiratory disease in veterinarians. AB - In order to determine the effect of occupational animal exposure on the occurrence of respiratory disease, we studied 257 active veterinarians and 100 control subjects who had not had occupational animal contact. All participants provided a detailed medical history and underwent spirometry, skin tests, and determination of total serum IgE levels. Asthma was significantly more prevalent in veterinarians (16.3%) than in controls (6%), (P less than .05), as was infectious/obstructive respiratory disease, 10.5% in veterinarians, 3% in controls (P less than .025). Only 13 of 257 veterinarians had respiratory symptoms related to animal contact; of these, seven experienced only allergic rhinitis while six reported both asthma and rhinitis. Animal-related allergic rhinitis was found more frequently in laboratory animal veterinarians than among veterinarians in farm, pet, or poultry practice. No symptoms typical of hypersensitivity pneumonitis were reported in veterinarians, nor were precipitins to animal antigens demonstrable. PMID- 4025959 TI - Routine use of skin testing for immediate penicillin allergy to 6,764 patients in an outpatient clinic. AB - A population of 6,764 individuals who had received a penicillin prescription at an outpatient clinic was tested with MDM (minor determinant mixture) and PG (penicillin G), whether or not a previous history of allergy to penicillin had been reported. Ninety-six (1.4%) patients showed positive skin tests. The 6,668 patients with negative tests were treated with penicillin and none showed any immediate allergic reaction. Because of the large size of the sample it was possible to calculate that the probability of risk of systemic reactions among patients with negative tests who were immediately treated with penicillin was 1.5/million. The method used is simple to carry out and has proved to be safe and reliable for the identification or exclusion of immediate allergic reaction to penicillin. PMID- 4025961 TI - Interpretation of bronchodilator responses. PMID- 4025960 TI - A new method of estimating bronchial hyper-responsiveness in younger children. AB - By using the new device, the "Astograph," it is possible to measure the continuous changes of respiratory resistance (Rrs) during bronchial inhalation challenge. This method, however, is not suitable for younger children because of wide variations in Rrs. So we studied a technique using a transcutaneous oxygen pressure (tcPO2) monitoring system. The bronchial reactivity and sensitivity were significantly correlated between Rrs and tcPO2 (P less than .001), and there was no correlation between cardiac output and Rrs. The tcPO2-method is useful for measuring bronchial responsiveness, especially in younger children. PMID- 4025962 TI - XII International Congress of Allergology & Clinical Immunology. October 20-25, 1985, Washington, D.C. Scientific program and abstracts of papers. PMID- 4025963 TI - [Course of the concentration of serum free amino acids as a function of time and the method of preservation]. AB - In order to determine the optimal conditions for storage in the case of deferred serum amino acid assay, the authors studied the effect of storing the sample for four hours at two different temperatures: melting ice and ambient temperature, as well as the effect of storing the amino acids for three months according to four methods of storage; freezing at -20 degrees C and -80 degrees C of deproteinised and non-deproteinised serum. When the analysis was performed within four hours of collection of the specimen, the best conditions are obtained when the sample is kept at the temperature of melting ice. The optimal conservation consists of immediately deproteinising the sample and storing it frozen for 14 days. PMID- 4025964 TI - [Aminopenicillin crystalluria: identification by infrared spectrophotometry]. AB - Renal stones and crystalluria can be characterized unambiguously by global physical methods. The authors report four cases of crystalluria induced by aminopenicillin (ampicillin and amoxicillin). Identification of these drug induced crystalluria was made by high-pressure liquid chromatography and infrared spectrophotometry. The physico-chemical data and infrared absorption characteristics can give us diagnostic for various forms of ampicillin and amoxicillin. PMID- 4025965 TI - [A specific spectrophotometric method for determining plasma and/or serum hemoglobin. Use of the chromogen 2,2'-azino-di-(3-ethylbenzothiazoline)-6 sulfonate (ABTS)]. AB - The authors describe a method for the determination of the plasma and/or serum haemoglobin, based on the peroxidase properties of the Haemoglobin-Haptoglobin complex, following the action of a solution of ABTS and hydrogen peroxide. The colour observed after a defined period of time is measured by spectrophotometry at 402 nm and is proportional to the haemoglobin concentration of the sample. A statistical study of the plasma haemoglobin concentration performed in male and female blood donors aged between 18 and 60 years is also presented. PMID- 4025966 TI - [Local anesthetics: simultaneous HPLC determination of lidocaine (Xylocaine) and bupivacaine (Marcaine) in human serum]. AB - In order to monitor loco-regional anaesthesia in the upper limbs with a combination of two anaesthetics, the authors participated in a clinical pharmacology study. They describe a method of simultaneous assay of bupivacaine and lignocaine by direct phase HPLC. In particular, the use of heptane sulfonic acid (counter-ion) in the mobile phase allows the elution of the local anaesthetics to be controlled. The criteria of reliability studied enable this technique to be considered for routine use. PMID- 4025967 TI - [Is it more valuable to determine LDL cholesterol or to calculate it?]. PMID- 4025968 TI - Proceedings of the 1985 UAEM/IRIEM research symposium on resuscitation. Orlando, Florida, February 7-8, 1985. PMID- 4025969 TI - Beneficial effect of epinephrine infusion on cerebral and myocardial blood flows during CPR. AB - It is hypothesized that epinephrine improves the ability to resuscitate the heart through a mechanism thought to be related to the increase in aortic pressure. Our results with epinephrine infusion during CPR are consistent with this hypothesis. Epinephrine selectively increased vascular resistance in noncerebral, noncoronary vascular beds, as indicated by a decrease in microsphere-determined blood flow in these areas. This increased vascular resistance raised aortic pressure during the chest compression phase and the relaxation phase of CPR. Because intracranial and right atrial pressures were only slightly higher with epinephrine, cerebral and myocardial perfusion pressures and blood flows were significantly improved. This beneficial effect (compared to no administration of a vasopressor) was more pronounced as CPR progressed beyond ten minutes. Enhanced cerebral and myocardial perfusion occurred with epinephrine when either the conventional or simultaneous compression and ventilation (SCV) mode of CPR was employed in dogs. Similar selective perfusion was sustained for 50 minutes of SCV-CPR with epinephrine, even when the onset of CPR was delayed five minutes. Regional brain blood flow differed in the delayed-CPR group in that cerebellum, brain stem, and thalamic regions initially had higher blood flows. In an infant animal model of CPR using conventional CPR in piglets, epinephrine also was found to increase cerebral and myocardial blood flows. These results show that administration of epinephrine benefits different age groups of different species with different modes of CPR; that benefits occur even with delayed onset of CPR which is associated with additional anoxia and acidosis; and that epinephrine administration is particularly effective in sustaining cerebral and coronary perfusion during prolonged CPR. PMID- 4025970 TI - Comparison of clinical CPR studies in Milwaukee and elsewhere in the United States. AB - As we mark the 25th anniversary of the clinical application of closed-chest cardiopulmonary resuscitation (SCPR), it is time to look back and analyze the progress we have made in the resuscitation of sudden death syndrome. Recent studies of SCPR's effectiveness have yielded mixed results, in comparison to early studies that were universally favorable. The continued toll of neurologic injury following SCPR resuscitation, and reinforcement of the importance of defibrillation in resuscitation, stimulate us to find improved forms of SCPR and improved methods of resuscitation delivery in emergency medical systems. PMID- 4025971 TI - Automatic external defibrillators: clinical, training, psychological, and public health issues. AB - Automatic external defibrillators (AEDs) will be used by spouses, family members, emergency first-responders, and the citizenry at large. Such use, however, raises a number of clinical, training, psychological, and public health issues. Clinical issues: Is cardiac arrest to be verified by the operator or the AED? Second verification systems, such as breath detectors, produce errors of omission, but greatly expand the pool of potential users. The relative merits of high sensitivity and low specificity in arrest verification must be defined by clinicians relative to the setting and the potential users. AEDs require cessation of basic CPR during their assessment periods; clinicians must determine the tradeoff between long interruption of basic life support and much earlier delivery of countershocks. Training issues: Criteria for those to be trained include consideration of who the patient will be and who the AED operator might be. AEDs pose a familiar adult education problem, that is, acquisition of a new psychomotor skill and retention of that skill for long periods before performance. What are the best teaching techniques? Currently available AEDs have different designs for device-operator interaction. Which design is most likely to assure proper performance during an actual arrest? Psychological issues: What are the psychological effects of learning about, living with, and eventually using an AED? The development of the automatic external defibrillator constitutes the most recent attempt to achieve early defibrillation of patients in cardiac arrest. The potential public health effect of such devices is enormous. PMID- 4025972 TI - Red cell substitutes: an update. AB - The two acellular oxygen carriers currently being evaluated as red cell substitutes are hemoglobin solutions and fluorocarbon emulsions. We have shown that both products can maintain normal levels of oxygen consumption, CO2 production, and circulatory dynamics in primates in the virtual absence of the red blood cell. Although each solution thus satisfies the most important criteria for a red cell substitute, development continues with both products. The clinical trials with the fluorocarbons have been discontinued due to the lack of efficacy of Fluosol-DA--20% in the setting of acute blood loss. Our current hemoglobin preparation is a polymerized, pyridoxylated product that has a normal oxygen carrying capacity. Clinical testing must await further evaluation of the safety and efficacy of this product. Alternative uses for both of these oxygen carriers continue to be explored, and may eventually be the area of their greatest utility in the clinical setting. PMID- 4025973 TI - Postischemic tissue injury by iron-mediated free radical lipid peroxidation. AB - Cell damage initiated during ischemia matures during reperfusion. Mechanisms involved during reperfusion include the effects of arachidonic acid and its oxidative products prostaglandins and leukotrienes, reperfusion tissue calcium overloading, and damage to membranes by lipid peroxidation. Lipid peroxidation occurs by oxygen radical mechanisms that require a metal with more than one ionic state (transitional metal) for catalysis. We have shown that cellular iron is delocalized from the large molecules where it is normally stored to smaller chemical species during postischemic reperfusion. Postischemic lipid peroxidation is inhibited by the iron chelator deferoxamine. Intervention in the reperfusion injury of membranes by chelation of transitional metals is a new and promising therapeutic possibility for protection of the heart and brain. PMID- 4025975 TI - Motor vehicle safety. American College of Emergency Physicians. PMID- 4025974 TI - Mitochondrial damage during cerebral ischemia. AB - Cerebral ischemia causes a rapid decline in the ability of brain mitochondria to synthesize adenosine triphosphate when they are exposed to oxygen and oxidizable substrates. Ischemia also results in a decreased capacity for energized mitochondria to sequester the abnormally high levels of calcium that are present within ischemic tissue. The degree to which these processes are affected is likely to influence the maintenance of cell viability during cerebral resuscitation. Factors that have been proposed to account for mitochondrial damage during ischemia and reperfusion include intracellular acidosis, Ca2+ induced membrane damage, and free-radical-dependent membrane lipid peroxidation. Ongoing research indicates that measures can be taken to manipulate these factors so that mitochondrial damage may be minimized and cell viability optimized during resuscitation. PMID- 4025976 TI - Rocky Mountain high. PMID- 4025977 TI - Factitious arrhythmia. PMID- 4025978 TI - Airway obstruction from metastatic melanoma. PMID- 4025979 TI - A hemodynamic model for anaphylactic shock. AB - The treatment of cardiovascular collapse and anaphylactic shock is largely empiric. A simple animal model was developed to evaluate the hemodynamic alterations in anaphylaxis. Eight adult New Zealand white rabbits of both sexes were studied. All animals weighed 3.8 kg to 5.3 kg. Sensitization was accomplished with a 2-mL subcutaneous dose of horse serum followed in two days with a 2-mL intravenous (IV) dose. At least 14 days elapsed after the IV dose before a 1-mL challenge dose of horse serum was given. On the day of the challenge dose, a femoral arterial catheter, arterial temperature probe, and right atrial catheter were placed under methoxyflurane anesthesia. The temperature probe was positioned in the aortic arch. The methoxyflurane was discontinued and the only sedation given during the shock phase was IV diazepam (0.1 mg/kg to 0.5 mg/kg). At least 30 minutes after methoxyflurane was discontinued, the challenge dose of horse serum was given through the right atrial catheter. Before and during the shock phase cardiac rhythm, arterial pressure, and intravascular temperature were monitored continuously. Cardiac outputs (CO) were performed by a thermodilution technique using 0.8 mL room temperature saline injectate through the right atrial catheter. Temperature deflection of the aortic probe was recorded and cardiac output was calculated. After giving the challenge dose, CO was measured at three, five, ten, 15, 25, 35, 45, and 60 minutes. All eight animals showed a significant (P less than .0005) fall in CO, cardiac index, and blood pressure within three minutes. The fall in cardiac index was 50% or more in all animals. Two animals died as a result of shock.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4025980 TI - Continuous monitoring of tissue pH with a fiberoptic conjunctival sensor. AB - To assess the relationship between conjunctival pH (pHcj), arterial pH (pHa), and cardiorespiratory variables during normal and low-flow conditions, hemorrhagic hypotension was induced in eight dogs. Conjunctival pH became significantly less than control values after a hemorrhage volume of 15 mL/kg (P less than .05); mean arterial pressure (MAP) did not fall until blood loss was 20 mL/kg. There was poor correlation between pHcj and pHa, cardiac index (CI), or MAP. There was a high degree of correlation, however, between pHcj-pHa difference (delta pH) and MAP (r = -0.886), CI (r = -0.846), and tissue oxygen extraction ratio (r = .896). The results of these experiments indicate that pHcj is a sensitive monitor of peripheral tissue perfusion, and that the degree of physiologic compromise associated with hemorrhage can be determined by analysis of the difference between arterial and conjunctival pH. PMID- 4025981 TI - An evaluation of carboxyhemoglobin spot tests. AB - A number of spot tests for carboxyhemoglobin are described in the emergency medicine literature. Four of these tests were evaluated for specificity, sensitivity, ease of performance, and ease of interpretation. Second- and third year emergency medicine residents were given samples of blood and asked to perform each of four spot tests on the samples. They were told that the samples may or may not contain carboxyhemoglobin. The reagents and instructions were available, but no technical assistance was given. The residents were asked to record the results of the tests and to answer a questionnaire. The test results were analyzed by linear regression and within-run precision. The available spot tests found in the literature were unable to determine accurately clinically significant levels of carboxyhemoglobin. The evaluators believed that the tests required a minimum of technical expertise and were easy to perform and interpret. None of the evaluators had any prior experience with carboxyhemoglobin spot tests. PMID- 4025982 TI - Utilization of medical care in Orange County: the effect of implementation of a regional trauma system. AB - To determine the effect of implementation of a regional trauma system on utilization of medical care we studied ambulance transports, emergency department (ED) visits, and hospital days for trauma and nontrauma patients before and after system implementation. Serious injury affects approximately one of every 1,000 persons each year and accounts for approximately one of every 250 ED visits, one of every 100 hospital days, and one of every 20 ambulance transports. Following system implementation the trauma hospitals experienced insignificant changes in annual percentage of market share of ED visits and hospital days and in annual rate of growth of ED visits and hospital days. We conclude that implementation of a medically directed regional trauma system has resulted in a predictable redistribution of a small number of seriously injured patients, and has not been associated with significant changes in utilization of EDs or hospitals. PMID- 4025983 TI - Hospital-based rotorcraft aeromedical emergency care services and trauma mortality: a multicenter study. AB - A group of 1,273 blunt trauma patients who were treated and transported from the site of injury by seven different hospital-based rotorcraft aeromedical emergency care services were studied using a methodology based on injury severity designed to predict the mortality of such patients. The methodology predicted that 241 patients should have died; 191 patients did die. This 21% reduction in expected mortality was highly significant (P less than .001). Each of the seven rotorcraft services had a reduction in predicted mortality. The reduction was statistically significant (P less than .05) in five of the seven aeromedical services, or 86% of the total patient cohort. Hospital-based rotorcraft aeromedical emergency care services may reduce the expected mortality of blunt trauma patients treated at the site of injury. PMID- 4025984 TI - The risk of percutaneous chest tube thoracostomy for blunt thoracic trauma. AB - Analysis of 164 percutaneous chest tube thoracostomies performed as a standardized technical procedure in the management of 129 blunt trauma victims demonstrated an overall complication rate of 9.1% (15 of 164). Three complications (1.8%) were related to problems of insertion, and four (2.4%) represented the problem of pneumothorax after chest tube removal. The remaining eight complications (4.9%) were associated with positive bacterial cultures, two (1.2%) of which represented clinical empyema. Both cases of empyema had either prolonged chest tube placement (23 and 15 days) or multiple chest tubes (two and three) on the same side. Percutaneous chest tube thoracostomy remains an important facet in the management of certain types of blunt thoracic trauma. Associated risks can best be minimized with adherence to a standardized technique and management protocol. PMID- 4025985 TI - Comparison of EMT blood pressure measurements with an automated blood pressure monitor: on scene, during transport, and in the emergency department. AB - Auscultation or palpation of blood pressure in critically ill patients by emergency medical technicians (EMTs) can be difficult, if not impossible, because of ambient noise, motion artifact, limited access to patients, or weak pulses. Automated blood pressure monitors (ABPMs) have been designed to overcome these problems during field emergencies and patient transport. Our study compared blood pressure measurements taken by EMTs with measurements provided by a Lifestat ABPM. Measurements in emergency patients on scene, during transport, in the emergency department (ED), and in a controlled environment were compared. Measurements in the various sites were obtained from 57 patients, and provision was made for two measurements at each site. Comparison of on-scene systolic blood pressures yielded a mean absolute systolic difference of 10.46 +/- 1.42 mm Hg and a mean absolute diastolic difference of 9.33 +/- 1.32 mm Hg. During transport systolic pressures showed a mean absolute difference of 11.50 +/- 1.72 mm Hg, and diastolic pressures showed a mean absolute difference of 7.59 +/- 1.16 mm Hg. Mean absolute differences in the ED were 11.23 +/- 1.49 mm Hg systolic and 8.37 +/- 1.25 mm Hg diastolic. Ninety comparison measurements in a controlled environment yielded a mean absolute systolic difference of 8.74 +/- 0.87 mm Hg and a mean absolute diastolic difference of 7.97 +/- 0.72 mm Hg. Comparison of mean diastolic pressure differences between EMT and ABPM measurements in various settings revealed some small, but statistically significant, discrepancies that were not considered clinically relevant.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4025986 TI - Microwave warming of resuscitation fluids. AB - Hypothermia is a common complication in fluid resuscitation of the hypovolemic patient. Warm intravenous (IV) fluids have been shown to be a valuable adjunct in volume replacement to prevent this complication. A rapid method of warming IV fluids is the microwave oven. Heating time for liter bags of crystalloid to 39 C was determined to be two minutes at high power, 600 W. Fresh frozen plasma was thawed with five 30-second exposures to microwave radiation. Microwave warming of packed red blood cells (PRBC), 4 C to 37 C, resulted in a 17-fold increase in plasma hemoglobin over that of water bath controls, (P greater than .01). Heating on a warm cycle to room temperature, 21 C, caused an average 26% increase in plasma hemoglobin. Therefore, we do not advocate microwave warming of PRBC because of the possible danger of local overheating, which causes hemolysis. We warm PRBC secondarily by diluting with microwave-warmed, calcium-free crystalloid. PMID- 4025987 TI - Reporting methodology protocols in three acute care journals. AB - Our study compared the reporting of methodology protocol details in three acute care journals, Annals of Emergency Medicine, Critical Care Medicine, and Journal of Trauma. Eleven criteria previously reported for evaluation of clinical trials in the medical literature were used. These were eligibility criteria, admission before allocation, random allocation, method of randomization, patients' blindness to treatment, blind assessment of outcome, treatment complications, loss to follow-up, statistical methods, statistical analysis, and power. All prospective, interventional, controlled trials appearing in the journals from January 1980 to June 1983 were identified. A total of 45 trials was found. Each study was read independently by two reviewers to determine whether each of the 11 criteria was reported clearly, reported unclearly, or not applicable. Disagreements were resolved by a third reader (adjudicator). The results are reported as the mean proportion of items clearly reported plus or minus the standard deviation: Annals of Emergency Medicine (n = 16), 0.40 +/- 0.18; Journal of Trauma (n = 18), 0.41 +/- 0.24; Critical Care Medicine (n = 11), 0.35 +/- 0.18. A one-way analysis of variance found no statistically significant difference between journals with respect to these proportions (P = .75). The study reveals that these journals, as judged by these criteria, do not report enough methodologic information to allow assessment of bias-reducing techniques and statistical methodology. PMID- 4025988 TI - Intraosseous infusion: an alternative route of pediatric intravascular access. AB - Substantial difficulties can be encountered when establishing rapid intravascular access in critically ill children. The historic technique of tibial intraosseous infusion is presented as an alternate intravenous route in children less than 3 years old. Review of the literature reveals this technique to be a rapid, reliable method with an acceptably low complication rate. Substances absorbed through the marrow, flow rates, technical difficulties, and complications are discussed. PMID- 4025989 TI - Abdominal aortic aneurysm with aortocaval fistula: an unusual cause of dyspnea and edema. PMID- 4025990 TI - Attending coverage. PMID- 4025991 TI - Intravenous mushroom poisoning. AB - Mushrooms of the genus Psilocybe frequently are ingested by recreational drug users for their hallucinogenic effects. We present the case of a 30-year-old man who allegedly received an intravenous injection of an extract of Psilocybe mushrooms. His clinical course was characterized in part by vomiting, severe myalgias, hyperpyrexia, hypoxemia, and mild methemoglobinemia, and it was similar to two previously reported cases. The patient improved rapidly with supportive care. PMID- 4025992 TI - Methylene chloride inhalation: an unusual form of drug abuse. AB - Methylene chloride is a chlorinated hydrocarbon used widely in home and industry. Its intentional abuse has not been reported previously. We describe the case of a 14-year-old boy who presented with lethargy, nausea, and chills six hours after the intentional inhalation of a household product containing methylene chloride. The patient's elevated carboxyhemoglobin level responded well to 100% oxygen therapy. The pathophysiology and treatment of methylene chloride are discussed. PMID- 4025993 TI - Larval conjunctivitis: a case report. AB - Presented is a case of acute bilateral conjunctivitis in a healthy 28-year-old man with signs and symptoms resembling those of catarrhal conjunctivitis but resulting from infestation with larvae of the sheep nasal botfly. The patient was treated with neomycin ointment and neomycin/hydrocortisone ophthalmic solution. While not a common cause of conjunctivitis, larval conjunctivitis requires prompt identification in order to institute specific and unique therapy that will prevent serious morbidity. PMID- 4025994 TI - Osteomyelitis of the cervical spine: reversible quadraplegia resulting from Philadelphia collar placement. AB - Pyogenic osteomyelitis of the vertebrae accounts for 4% of all osteomyelitis, and is believed to be increasing in incidence. Pyogenic osteomyelitis of the cervical spine is even more uncommon, accounting for 10% of all spinal pyogenic osteomyelitis. Presented is a case of pyogenic osteomyelitis of the cervical spine in which appropriate methods of immobilization of the cervical spine resulted in a surgically reversible acute deterioration of the patient's neurologic status. While immobilization of the cervical spine remains the initial treatment of choice in most patients with suspected disease of the cervical spine, it is not without potential complications. PMID- 4025995 TI - Blunt abdominal trauma causing jejunal rupture. AB - Two cases of jejunal rupture from blunt abdominal trauma are described. One followed a motorcycle accident, and the other followed a punch to the abdomen. Both patients initially had unremarkable abdominal examinations. After surgical repair of the ruptures, the patients recovered uneventfully. Jejunal rupture secondary to blunt abdominal trauma is not common, but its subdued clinical presentation and the nonspecific laboratory findings make diagnosis difficult. High morbidity and mortality are associated with this type of injury when diagnosis and treatment are delayed. Small bowel rupture should be considered in any patient with a history of significant blunt abdominal trauma and persistent abdominal pain. PMID- 4025996 TI - Medical, moral, legal, and ethical aspects of resuscitation for the patient who will have minimal ability to function or ultimately survive. American College of Emergency Physicians, Dallas, Texas. PMID- 4025997 TI - Proving the efficacy of hospital-based HEMS. PMID- 4025998 TI - Residency essentials: quantify to assure quality. PMID- 4025999 TI - Trauma systems and their meaning. PMID- 4026000 TI - Asthma guidelines. PMID- 4026001 TI - Wound ballistics, round 3. PMID- 4026002 TI - COWS caloric test. PMID- 4026003 TI - Isolation of mononuclear cells from bovine milk by continuous-flow and density gradient centrifugation: response of cells to mitogens. AB - Continuous-flow centrifugation (CFC) and 2 types of discontinuous density gradients (Ficoll-diatrizoate or polyvinylpyrrolidone-coated colloidal silica) were used to obtain bovine mononuclear cells from milk. Determinants considered were efficiency of cell recovery, cell viability, and functional activity of the enriched cell population in a lymphocyte blastogenesis (LBT) assay. Milk leukocytes were recovered by CFC with an efficiency of 46% and a viability of 63%. Selective loss of a cell population due to CFC was not observed. Using density gradients, enrichment was marginally effective (73% mononuclear cells with polyvinylpyrrolidone-coated colloidal silica and 82% mononuclear cells with Ficoll-diatrizoate) and overall mononuclear cell efficiency of recovery was reduced. In comparison, using either density gradient, blood mononuclear cells were harvested with efficiencies of 61.5% and 63.4%, with 85.6% and 89.3% viability and greater than 99% purity. Compared with peripheral blood lymphocytes, milk mononuclear cells were less viable. When evaluated using the LBT assay, milk mononuclear cells were hyporesponsive to mitogenic stimulation, regardless of the density gradient used. The methods used allowed for the collection of a sufficient number of nonelicited milk mononuclear cells for replicate evaluation of several mitogens or antigens, using the LBT assay. Mononuclear cells recovered had a consistently reproducible blastogenic response to T-cell mitogens. PMID- 4026004 TI - Pharmacokinetics of gentamicin at steady-state in ponies: serum, urine, and endometrial concentrations. AB - Gentamicin (GT) was administered IM to 6 healthy mature mare ponies at a dosage of 5 mg/kg of body weight every 8 hours for 7 consecutive days (total, 21 doses). Two venous blood samples were collected before (trough) and at 1 hour (peak) after the 5th, 10th, 14th, and 19th doses. An endometrial biopsy was done of each mare on days 4 and 7. On the 7th day, just before the 21st administration of GT, base-line blood samples were collected, and 22 blood samples were collected over a period of 48 hours after GT was given. The mares were catheterized on the 7th day, and urine was collected for 24 hours. Serum, urine, and endometrial GT concentrations were determined by a radioimmunoassay technique (sensitivity of 0.3 micrograms/ml of serum). Serum GT concentration data obtained from the terminal phase were best fitted by a 1-compartment open model with a biological half-life of 2.13 +/- 0.43 hours. Total body clearance and renal clearance were 1.69 +/- 0.41 and 1.40 +/- 0.26 ml/min/kg, respectively. Mean endometrial concentrations on day 4 and day 7 were 5.02 +/- 3.3 and 12.75 +/- 1.6 micrograms/g. To achieve mean serum GT concentrations (micrograms/ml) at steady state of 6.47 +/- 1.51, a maximum steady-state concentration of 12.74 +/- 1.60, and a minimum steady-state concentration of 1.43 +/- 0.57, a dosage of 5 mg/kg every 8 hours is recommended. Serum urea nitrogen, serum creatinine, and the fractional clearance of sodium sulfanilate were determined before and after GT treatment. Renal function remained within the base-line range during 7 days of GT administration. PMID- 4026005 TI - Photomicrographic evaluation of stallion spermatozoal motility characteristics. AB - A photomicrographic method for evaluation of stallion spermatozoal motility was developed, and spermatozoal image and velocity characteristics were defined. The photomicrographic method was compared with visual estimation of motility in the same semen sample over time. Using photomicrography, velocities and percentages of individual spermatozoal image characteristics were determined. Although there was a high correlation between results of the 2 methods, results of the photomicrographic method were more repeatable than were those of the visual method. PMID- 4026006 TI - Antagonism of xylazine-pentobarbital anesthesia by yohimbine in ponies. AB - Effects of yohimbine on xylazine-pentobarbital anesthesia were evaluated in ponies. Five minutes after the IV injection of xylazine (1.1 mg/kg of body weight), pentobarbital sodium (12.7 mg/kg, IV) and additional xylazine (2.2 mg/kg, IM) were given and produced anesthesia in 12 ponies for 64.0 +/- 16.4 minutes (mean +/- SD) as well as immobilization for 89.8 +/- 34.2 minutes. Eleven ponies were given yohimbine (0.1 mg/kg, IV) 50 minutes after pentobarbital dosing. In these 11 ponies, durations of anesthesia and immobilization were shorter, 52.0 +/- 1.4 and 65.5 +/- 14.8 minutes, respectively. The xylazine pentobarbital combination caused bradycardia that was reversed by yohimbine injection. Xylazine-pentobarbital produced a small, but steady, decrease of mean arterial blood pressure, which was compounded by yohimbine administration and was evident for approximately 2 minutes. Within a minute after yohimbine injection, the ponies' respiratory rate decreased and the length of inspiration and expiration and thoracic breathing increased. This lasted approximately 2 to 3 minutes and was followed by an increase in respiratory rate. The anesthesia also produced a decrease in PaO2 that gradually returned to base line in 12 control ponies, but was more pronounced in 11 ponies given yohimbine. The PaCO2, although remaining moderately high in control ponies, returned to base line after yohimbine injection. An increased pHa was seen 60 minutes after induction of anesthesia and was especially noticeable after yohimbine administration. Decreases in the number of WBC, hemoglobin content, PCV, plasma protein and serum aspartate transaminase resulting from xylazine-pentobarbital were reversed by yohimbine. Conversely, serum glucose values and creatine kinase activities were increased by xylazine-pentobarbital.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4026007 TI - Observations of fracture of the anconeal process of the ulna of swine. AB - Fractures of the anconeal process of 5 pigs ranging in age from 4 to 8 months were studied radiographically and histologically. Clinically, animals with a fracture of the anconeal process had a "tight," restricted gait. In pigs at 4.5 months of age, a radiolucent line through the base of the anconeal process was composed of fibrocartilage, fibrous connective tissue, and hyaline cartilage. Subperiosteal proliferation of woven bone was located along the cranial surface of the olecranon, adjacent to the base of the anconeal process. In older animals, the radiolucent line through the anconeal process contained variable amounts of fibrous connective tissue and fibrocartilage. The proliferation of subperiosteal bone at the base of the anconeal process formed a "buttress callus" which retained a radiolucent area between the callus and the proximal surface of the anconeal process. The latter region of radiolucency was continuous with the transversely oriented line that traversed the base of the anconeal process. PMID- 4026008 TI - Compartmental and noncompartmental pharmacokinetic analyses of minocycline hydrochloride in the dog. AB - Six adult dogs were given 5 mg of minocycline hydrochloride/kg of body weight IV. Pharmacokinetic evaluation of the serum drug concentration versus time data was performed, using the 2-compartment open model, the 3-compartment open model, and a noncompartmental model involving use of the statistical moment theory. All pharmacokinetic values except clearance were model independent. Minocycline half life ranged between 6.48 and 7.24 hours; volume of distribution at steady state, between 1.859 +/- 0.368 and 2.001 +/- 0.468 L/kg; and clearance, between 3.195 +/ 0.618 and 3.424 +/- 0.684 ml/min/kg. These data are similar to those reported for oxytetracycline and indicate that the frequency of administration of the 2 tetracyclines should be the same. Three of the 6 dogs developed an adverse response to the IV injection of minocycline. Dog 1 developed urticaria and had initial serum drug concentrations of approximately 2 times the mean concentrations for the other dogs; values were not included in the pharmacokinetic analysis. Two other dogs had transient signs indicating cardiovascular depression or hypotension; their data were included. Due to the frequency of the unexpected reactions found in this study, it was concluded that dogs should not be given minocycline rapidly IV. PMID- 4026009 TI - Evaluation of the zetacrit and zeta sedimentation ratio in dogs. AB - The Wintrobe erythrocyte sedimentation rate (ESR) has been used in animals and persons as a screening test for inflammatory disease and as a monitor for disease progression in individuals. Now, the zetacrit (ZC) and zeta sedimentation ratio (ZSR) are suggested as suitable rapid laboratory tests to replace the ESR in dogs. In 65 dogs, a strong inverse correlation between ESR and ZC was observed (r = -0.961, P less than 0.05). Significant correlations of similar magnitude between ZC and hematocrit (r = 0.587, P less than 0.05) and ESR and Hct (r = 0.569, P less than 0.05) were observed. In addition, influences of various protein fractions, such as fibrinogen, globulin, and albumin, on the ESR and ZC were evaluated and found to be of similar magnitude. These data indicate that ESR and ZC are equivalent methods for determining erythrocyte sedimentation rates in dogs. A strong correlation (r = 0.900, P less than 0.05) between Wintrobe ESR, adjusted for the effect of Hct (ESRHct), and ZSR was observed. The influence of plasma proteins on ESRHct and ZSR was of similar magnitude. However, a weak yet significant correlation between ESRHct and the microhematocrit remained (r = 0.291, P less than 0.05). Data indicate that the latter more effectively factors out the influence of Hct on sedimentation. PMID- 4026011 TI - Regional hypoxic pulmonary vasoconstriction in dogs with asymptomatic dirofilariasis. AB - The pulmonary hemodynamic response to unilateral alveolar hypoxia was investigated in pentobarbital-anesthetized dogs with mild heartworm (HW) disease and in dogs free of HW (HWF). Left lung nitrogen ventilation in HWF dogs resulted in a decrease in the fraction of the cardiac output (QT) perfusing the left lung (QL) from 0.37 +/- 0.03 (SEM) to 0.20 +/- 0.02 (P less than 0.01). In contrast, dogs with mild HW disease did not develop a significant decrease in QL/QT which decreased from 0.38 +/- 0.02 to 0.33 +/- 0.02. This attenuated pulmonary vascular response to regional alveolar hypoxia in dogs with HW disease was associated with a normal pulmonary arterial pressure (14.8 +/- 1.5 mm of Hg) that was not different from that seen in HWF dogs (15.8 +/- 1.7 mm of Hg). These results indicate that mild HW disease interferes with the ability of hypoxic pulmonary vasoconstriction to redistribute pulmonary blood flow away from hypoxic regions of the lung. PMID- 4026010 TI - Comparison of crystalloid and sanguineous cardioplegic solutions in the dog. AB - Myocardial protection provided by 2 types of cold cardioplegic solution and by cold saline solution was compared experimentally in dogs on cardiopulmonary bypass. Techniques and solutions used simulated clinical conditions. Serial biopsies of myocardium were assayed for adenosine triphosphate, adenosine diphosphate, and adenosine monophosphate. Maintenance and recovery of each phosphate was calculated as a percentage of the prebypass value for each type of solution; these values were used to compare the myocardial protection afforded by the 3 solutions. A difference in these values was not observed between the 2 types of cardioplegic solution; both values were greater than for the control solution, which may indicate improved myocardial protection with cardioplegic arrest. PMID- 4026012 TI - Tympanographic volume measurements of the canine ear. AB - External ear canal volumes of 50 dogs were measured by tympanography. Comparison between each dog's weight and ear volume revealed a linear increase in volume with increasing weight up to 10 kg. At weights greater than 11 kg, ear volumes did not increase. After ear canal measurement, the tympanic membranes of 30 of the dogs were punctured, permitting determination of the combined volumes of the external ear canal and middle ear. This combined volume increased with increasing weight. PMID- 4026013 TI - Nicotinamide-adenine dinucleotide-methemoglobin reductase activity in erythrocytes from cats. AB - Reduced nicotinamide-adenine dinucleotide (NADH)-methemoglobin reductase activity in feline erythrocyte lysates was determined, using potassium ferricyanide as substrate. The optimum conditions for the assay were pH 8 and 37 C. Mean NADH ferricyanide reductase activity in cats was 15.7 +/- 4.1 mumoles of substrate converted/g of hemoglobin/min. The migration of NADH-ferricyanide reductase was similar to that of the NADH-methemoglobin reductase (NADH diaphorase) on starch gel electrophoresis. PMID- 4026014 TI - Serum concentrations of gentamicin in cats. AB - Twenty-one adult cats, allotted into 2 groups, were given gentamicin sulfate at dosages of either 5.0 mg/kg of body weight or 2.5 mg/kg as a single IM injection. During a 24-hour period, serum concentrations of gentamicin were measured serially, using a fluorescence immunoassay. The mean peak serum concentration of gentamicin in cats given 5.0 mg/kg was 23.1 micrograms/ml at postinjection hour (PIH) 0.5; thereafter, the mean serum concentration steadily decreased to 2.0 micrograms/ml at PIH 24. The mean peak serum concentration for cats administered 2.5 mg/kg was 9.1 micrograms/ml at PIH 0.5; thereafter, the mean serum concentration steadily decreased to 1.3 micrograms/ml at PIH 12. Serum therapeutic concentrations, without exceeding toxic concentrations, were attained at the 2.5 mg/kg dosage. PMID- 4026015 TI - Induction of cleft palate in newborn pigs by maternal ingestion of poison hemlock (Conium maculatum). AB - Cleft palates were induced in newborn pigs of gilts fed Conium maculatum seed or plant during gestation days 30 through 45. Twelve of 23 newborn pigs born to 3 gilts given Utah-grown C maculatum seed and 9 of 12 newborn pigs born to a single gilt given the fresh Utah spring-growth C maculatum plant had cleft palates. The cleft palates ranged from a unilateral cleft, involving only 1 side of the palate, to a full bilateral cleft. Brachygnathia was also observed in some of these newborn pigs with cleft palate. Other malformations were not observed. Chemical analysis of seed and plant samples indicated that gamma-coniceine was the responsible teratogenic alkaloid. A daily dose of plant or seed that provided greater than or equal to 1.07 mg of gamma-coniceine/kg of body weight fed to gilts during the 30th through the 45th day of pregnancy resulted in teratogenic effects. PMID- 4026016 TI - Correlation of noninvasive surface temperature measurement with rectal temperature in swine. AB - Skin and rectal temperature measurements were taken on 15 crossbred sows and gilts (225 kg) during the last 5 days of prepartum period and compared with those recorded in the first 8 days after parturition. The correlation of skin and rectal temperature values was not good during either period, although an increased correlation was noted in the postparturient period. The rectal temperature significantly (P less than 0.05) increased in the postparturient period, but the mean surface temperature was unchanged. This would indicate a decreased blood flow to the surface, since an equivalent blood flow to the surface after a rectal temperature increase would result in a concomitant mean surface temperature increase. The decreased flow to the surface of the animal was selective, since a significant (P less than 0.05) decrease in surface temperature was noted at the tailhead, perineum, vulva, mammae-caudal, and eye, whereas the surface temperature of the mammae-cranial and mammae-middle was significantly (P less than 0.05) increased. PMID- 4026017 TI - Comparison of carbonated lidocaine and lidocaine hydrochloride for caudal epidural anesthesia in horses. AB - A double-blind comparison of carbonated lidocaine and lidocaine hydrochloride in caudal epidural anesthesia was performed in 8 horses. Among 5 horses with successfully paired bilateral caudal epidural blockades, no significant differences in onset time, duration, or sensory blockade were demonstrated. In the present study, carbonated lidocaine did not offer an advantage over the hydrochloride salt for caudal epidural anesthesia in the horse. PMID- 4026018 TI - Suppression of mitogenic response of bovine lymphocytes during experimental ketosis in calves. AB - Experimental ketosis was induced by feeding calves a diet containing 1,3 butanediol for 9 or 10 days. Blood beta-hydroxybutyrate was significantly (P less than 0.05) elevated during clinical ketosis. The mitogenic response of the lymphocytes collected during ketosis was significantly (P less than 0.01) suppressed, and the suppression persisted for 2 weeks. During ketosis, all calves fed a 1,3 butanediol diet had clinical signs of an upper respiratory tract infection. Possible relationships between the suppressed function of lymphocytes, the increased concentration of 1,3 butanediol, and the increased susceptibility of the calves to infections during ketosis were considered. PMID- 4026020 TI - Comparative pharmacokinetics of febantel and its metabolites in sheep and cattle. AB - The pharmacokinetics of febantel and its main metabolites were studied in cattle and sheep. Seven ewes and 4 heifers were given febantel orally in a single dose of 7.5 mg/kg, 25 mg/kg, or 45 mg/kg of body weight. Plasma concentrations vs time of febantel and individual metabolites were determined by high-performance liquid chromatography analysis. Intestinal absorption of febantel was faster and biotransformations were more active in sheep than in cattle. PMID- 4026019 TI - Borrelia theileri: isolation from ticks (Boophilus microplus) and tick-borne transmission between splenectomized calves. AB - The bovine spirochete, Borrelia theileri, was detected in Giemsastained blood smears from a splenectomized calf 17 days after exposure to a laboratory colony of the tropical cattle tick, Boophilus microplus. Spirochetes were detected in the hemolymph and ovary of all engorged female ticks examined, indicating a high infection rate in this tick colony. Spirochetes were detected in a 2nd splenectomized calf 15 days after exposure to the larval offspring of ticks from the 1st calf. The only observable effect of infection in the 2 calves was a maximum rectal temperature increase to 40.2 C, which coincided with the first detectable parasitemia. The tick colony did not have any adverse effects, despite extensive multiplication of spirochetes in their tissues. PMID- 4026021 TI - Percutaneous trephine biopsy of the vertebral body in the rhesus monkey (Macaca mulatta). AB - Two methods of percutaneous vertebral body biopsy were performed in the Rhesus monkey, using a 3-mm diameter trephine and a pneumatic driver placed at a 30 degrees angle of approach to the transverse plane of the spine. The freehand method involved placing needle landmarks in the spine, followed by examination of a lateral radiograph of the lumbar region to verify landmark positioning and to estimate placement of the trephine. In the 2nd method, a pneumatic trephine guide was oriented according to a trigonometric calculation based on radiographic data. The pneumatic trephine guide allowed precise placement of the driver and steadied the trephine as it passed through the bone. PMID- 4026022 TI - Creatine kinase isoenzymes in bovine tissue. AB - Brain, heart, liver, kidney, spleen, lungs, rumen, abomasum, small intestine, skeletal muscle, and urinary bladder from healthy cattle were analyzed for creatine kinase isoenzymes as a possible aid in the diagnosis of myocardial disease. Creatine kinase was detected in all organs evaluated. In addition, 6 different fluorescing bands were detected by isoenzyme analysis. Large quantities of the same isoenzymes were in cardiac and skeletal muscle, but not in other organs. Creatine kinase isoenzyme analysis does not necessarily indicate cardiac damage, but may narrow the range of tissue damage possibilities to be included in the differential diagnosis. PMID- 4026023 TI - Effect of wound location and the use of topical collagen gel on exuberant granulation tissue formation and wound healing in the horse and pony. AB - Preformed collagen gel was topically applied to cutaneous wounds of the equine dorsal fetlock (thoracic limb) and metatarsal regions to evaluate the effect on exuberant granulation tissue production and wound healing. In 6 horses and 3 ponies (less than 140 cm high at the withers and less than 365 kg), 36 standardized cutaneous limb wounds were surgically induced (4 wounds/animal); 18 wounds were treated topically with collagen gel, and 18 wounds were not treated (controls). Collagen gel was initially applied to the wound at 0, 2, or 7 days after wound formation (groups 1, 2, and 3, respectively). Four measurements were regularly made: amount of wound contraction and the size of the granulation bed, epithelial covering, and total wound. Sequential skin and wound biopsies were evaluated histologically to assess wound healing. Using a computer, data were analyzed for differences in the 4 measurements between treated and control wounds, between fetlock wounds and metatarsal wounds, and among groups 1, 2, and 3. Analyses were performed on days 15 and 45 of wound healing and on the final day of healing. A significant difference (P greater than 0.05) in the production of exuberant granulation tissue, rate of epithelialization, or degree of wound contraction was not detected between the collagen-treated and control wounds. Total healing time and final scar size were similar. Wound healing patterns were significantly different (P less than 0.05) in the fetlock wounds and metatarsal wounds. All wounds enlarged up to day 15 with fetlock wounds enlarging significantly more than did the metatarsal wounds.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4026024 TI - Brain stem auditory-evoked response in the nonanesthetized horse and pony. AB - The brain stem auditory-evoked response (BAER) was measured in 10 horses and 7 ponies under conditions suitable for clinical diagnostic testing. Latencies of 5 vertex-positive peaks and interpeak latency and amplitude ratio on the 1st and 4th peaks were determined. Data from horses and ponies were analyzed separately and were compared. The stimulus was a click (n = 3,000) ranging from 10- to 90-dB hearing level (HL). Neither horses nor ponies responded with a BAER at 10 dB nor did they give reliable responses at less than 50 dB. The 2nd of the BAER waves appeared in the record at lower stimulus intensities than did the 1st wave for the horse and pony. Horses and ponies had a decreasing latency for all waves, as a result of increasing stimulus intensity. Latencies were shorter for the ponies than for the horses at all stimulus intensities for the 1st, 2nd, 3rd, and 4th waves, but not the 5th wave. At 60-dB HL, the mean latencies for the 1st through 5th wave, respectively, for the horse were 1.73, 3.08, 3.93, 4.98, and 6.00 ms and for the pony 1.48, 2.73, 3.50, 4.56, and 6.58 ms. Interpeak latencies, 1st to 4th wave, averaged 3.22 ms (horse) and 3.11 ms (pony) for all stimulus intensities from 50- to 90-dB HL and had a tendency to decrease slightly as stimulus intensity increased. Amplitude ratios (4th wave/1st wave) were less than 1 for all stimulus intensities in the horse. In the pony, the ratio was less than 1 at greater than or equal to 70-dB HL and greater than 1 at less than or equal to 60-dB HL. PMID- 4026025 TI - Porcine malignant hyperthermia susceptibility: erythrocytic osmotic fragility. AB - Erythrocyte osmotic fragility was determined in 27 Pietrain swine which were susceptible to malignant hyperthermia (MH), 29 Yorkshire swine which were resistant to MH (controls), and 50 crossbred swine (Pietrain x Yorkshire), half of which were MH susceptible. Halothane challenge tests and blood creatine kinase activity were used as criteria for determining MH susceptibility. Mean values for osmotic fragility of erythrocytes in concentrations of NaCl between 60 and 120 mM were significantly different for the 3 groups (P less than 0.001). Hemolysis (50%) of erythrocytes occurred at NaCl concentrations of 90 mM for Pietrains, 85 mM for crossbreds, and 78 mM for controls. Increased fragility values occurred in 96% of the Pietrains, 3% of the controls, and 42% of crossbred swine that were halothane test-positive, and 58% of halothane test-negative crossbreds (P less than 0.05). The mean time of onset of signs of MH in response to halothane challenge testing was twice as long in the crossbreds as in Pietrains (P less than 0.01). Reticulocyte counts were moderately high in blood samples from both the Pietrains (P less than 0.001) and the crossbreds (P less than 0.05). Of the swine which were tested for erythrocyte selenium-dependent glutathione peroxidase activity, values were within acceptable laboratory limits in 18 of 20 Pietrains, 14 of 14 halothane test-negative crossbreds, and 8 of 8 halothane test-positive crossbreds. In 2 of 20 Pietrains, a 35% deficiency of this enzyme was found. Heinz bodies were not detected in erythrocytes examined from 21 Pietrains, 20 crossbred swine (8 halothane test positives), and 12 controls.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4026026 TI - Effect of transportation on cortisol concentrations and on the circadian rhythm of cortisol in gilts. AB - A study was conducted to determine whether the circadian rhythm of cortisol in gilts is disrupted or altered by transport. Sixteen ovariectomized gilts with indwelling jugular catheters were individually penned in an enclosed building (location 1). Blood samples were collected at 0700 and 1900 hours for 6 days. On day 7, gilts in groups of 4 were transported 5.6 km to environmentally controlled chambers (25 C) and were individually penned (location 2). On the day of transport, samples were collected at 0700 hours at location 1, immediately before and after transport in a trailer, after unloading at location 2, and at 1900 hours at location 2. For the first 6 days at location 2, blood samples were collected daily at 0700 and 1900 hours. For the 6 days at location 1, circadian rhythm was evidenced by higher cortisol concentrations in the AM hours than in the PM hours. During transport, serum cortisol concentrations increased (P less than 0.01). Highest concentrations developed at 0.5 hour after unloading; concentrations declined thereafter. During the first 6 days at location 2, circadian rhythm was evidenced by higher serum cortisol concentrations in the AM hours than in the PM hours. Therefore, the transportation of gilts 5.6 km to new pens was a transient stress causing a temporary increase in serum cortisol concentrations, but did not cause a disruption in the endogenous rhythm of cortisol. PMID- 4026027 TI - Effect of sodium heparin and antithrombin III concentration on activated partial thromboplastin time in the dog. AB - Regulation of blood coagulation was studied in 12 dogs, using subcutaneous administration of sodium heparin. Dosage of heparin needed to achieve the desired 1.5- to 2.5-fold increase in the activated partial thromboplastin time (APTT) was 250 to 500 IU/kg of body weight. Increased APTT lasted less than 6 hours. Repeated heparin administration, using the lowest dosage (250 IU/kg) every 6 hours, induced an unacceptable prolongation of clotting times during the first 2 days of treatment. Prolonged administration at a dosage of 200 IU/kg every 6 hours adequately maintained the desired hypocoagulative state initially; after 2 days, however, the prolonged APTT steadily decreased. The decreasing effect was proportionate to a decrease in plasma antithrombin III (AT III). To sustain a correctly balanced hypocoagulative state from prolonged subcutaneous administration of heparin, APTT values should be determined regularly to monitor therapy. In addition, transfusion of AT III-rich donor plasma may be necessary when low plasma AT III reduces the effects of heparin. PMID- 4026028 TI - Contractile responses to histamine of isolated pulmonary artery strips from healthy and heartworm-infected dogs. AB - Pulmonary artery strips from control and Dirofilaria immitis-infected dogs were tested for isometric contractile response to histamine, carbamylcholine, and norepinephrine. The strips from D immitis-positive dogs showed diminished response to histamine; a smaller percentage of the strips contracted, and the magnitude of the contraction was less than the response of the control strips to the highest concentration used. Carbamylcholine caused virtually no contractile effect in either group. Norepinephrine contracted all strips, even those not responding to histamine. A role for histamine in the pathogenesis of the pulmonary arterial lesions associated with dirofilariasis is presented. PMID- 4026029 TI - Anatomic predisposition to perianal fistulae formation in the German shepherd dog. AB - Gross and microanatomic features which may predispose the German Shepherd Dog to perianal fistulae formation were studied in 2 groups of clinically healthy dogs: a predisposed group (German Shepherd Dogs) and a control group comprising breeds not ordinarily affected by perianal fistulae. The dimensions of the anal crypts (depth, base width, and length), measured and compared statistically between samples, identified no significant variation between groups (P greater than 0.05). Major tissue components of the anal canal were measured microscopically and were similarly evaluated: epithelial height in each zone, thickness of the lamina propria in each zone, thickness of the internal and external anal sphincter muscles, and density of the circumanal, sebaceous, and apocrine sweat glands. The only significant finding was an increase in density of apocrine sweat glands in the zona cutanea in the pre-disposed dog group. In a semiquantitative analysis of the inflammatory responses frequently seen in the anal glands, more mature fibroplasia was seen in the German Shepherd Dogs, indicating that inflammation was more longstanding in this group. PMID- 4026030 TI - Echocardiographic reference values in healthy cats sedated with ketamine hydrochloride. AB - An M-mode echocardiographic examination was performed in a consistent manner in 30 clinically healthy cats under light ketamine hydrochloride sedation. There was a significant linear relationship between increasing body size and increasing cardiac dimensions for several echocardiographic values. Positive correlation existed between body weight and body surface area with aortic root, left ventricular caudal wall thickness (LVCW), interventricular septal thickness (IVS), IVS/LVCW, and mean velocity of circumferential fiber shortening (Vcf); there was a negative correlation between body weight and body surface area with left ventricular ejection time (LVET). Body surface area also correlated positively with percentage of ventricular minor axis dimensional change (% delta D). Positive correlations were recorded between left ventricular end-diastolic dimension (LVEDD) and left ventricular endsystolic dimension (LVESD), LVESD and LVET, LVCW and IVS, LVET (calculated by LVCW motion) and LVET (calculated by aortic valve motion), % delta D and Vcf, heart rate and Vcf, and Vcf (calculated using aortic valve motion to compute LVET) and Vcf (using LVCW motion to compute LVET). There were negative correlations between LVEDD and % delta D, LVEDD and Vcf, LVESD and Vcf, LVET and Vcf, LVET and heart rate, LVET and % delta D. Significant differences were recorded between means of echocardiographic reference values generated in this and other studies, except for LVESD. PMID- 4026032 TI - Intestinal phospholipase B activity in pigs inoculated with transmissible gastroenteritis virus. AB - Intestinal phospholipase B activity in pigs inoculated with transmissible gastroenteritis (TGE) virus was studied. Phospholipase activity was quantified by measuring the hydrolytic release of free fatty acids in homogenized intestinal tissue incubated with lysophosphatidylcholine. An increase in enzyme activity was observed in the cranial and caudal portions of the ileum and jejunum in pigs killed 3, 6, and 8 days after inoculation with TGE virus. Seemingly, phospholipase B may be part of the host immune response against TGE viral infection. PMID- 4026031 TI - Effects of various antidotal treatments on acetaminophen toxicosis and biotransformation in cats. AB - Oral N-acetylcysteine (NAC), IV NAC, and IV sodium sulfate were evaluated as treatments for cats dosed orally with toxic sublethal doses of acetaminophen (APAP). Six cats were given single oral doses of 120 mg of APAP/kg of body weight and the respective antidote at 4.5, 8.5, and 12.5 hours after APAP dosing in 3 separate trials. The cats were given each antidotal treatment in random order with at least 3 weeks separating the individual APAP-treated trials. Clinical signs, plasma APAP half-lives, clinical chemical values, and APAP urinary excretion and metabolites were studied. Results were compared (P less than 0.05) with each other and with those of a control group of 6 cats given identical APAP doses, but given no antidotal treatment. At the dosage levels used, oral NAC, IV NAC, and IV sodium sulfate were equally effective antidotes, as measured by decreased methemoglobinemia, increased whole blood reduced glutathione, decreased APAP half-lives, and increased urinary excretion of the APAP-sulfate conjugate. All the antidotal treatments produced results significantly different from those in the control cats. PMID- 4026033 TI - Effects of experimentally induced Isospora suis infection on morbidity, mortality, and weight gains in nursing pigs. AB - Forty-nine pigs from 6 litters were inoculated at 3 days of age with 300,000 sporulated oocysts of Isospora suis to determine the effects of neonatal coccidiosis on morbidity, mortality, and weight gain in nursing pigs. Fifty-one control pigs from 6 litters were not inoculated. Three to 5 days after inoculation, the inoculated pigs developed a nonhemorrhagic diarrhea, generally lasting 6 to 10 days, that lead to visible dehydration, loss of condition, and 20.4% mortality. Control pigs did not die or develop coccidiosis during the 3 week study and had significantly (P less than 0.05) greater body weights at 7, 14, and 21 days of age than did the inoculated pigs. PMID- 4026034 TI - Diagnosis of ovine fascioliasis by a dot enzyme-linked immunosorbent assay: a rapid microdiagnostic technique. AB - A microenzyme-linked immunosorbent assay (dot-ELISA) was modified for making an immunodiagnosis of Fasciola hepatica infections in sheep. Sheep were alloted as follows: group I-3 controls and 4 principals, each inoculated with 500 metacercariae; group II-3 controls and 7 principals, each inoculated with 250 metacercariae; and group III-3 controls and 7 principals, each inoculated with 500 metacercariae. Blood and fecal samples were collected from each animal every 2 weeks for 16 weeks. Presence (or absence) of flukes was confirmed by fecal examinations and examination of dissected livers at necropsy of the sheep. The dot-ELISA incubations were done at ambient room temperature. Nitrocellulose disks dotted with 1 microliter (50 ng of protein) of F hepatica excretory/secretory products were placed in 96-well tissue culture plates. After nonspecific binding sites on the disks were bound with bovine serum albumin-triethanolamine-buffered saline solution, dilutions (1:2) of positive- and negative-control serum samples or experimental serum samples were placed in appropriate wells for a 30-minute incubation. Wells were washed (3 times), and 50 microliters of horseradish peroxidase conjugated rabbit anti-sheep immunoglobulin G was added to each well for a 30-minute incubation and then aspirated. Substrate solution (4-chloro-1 naphthol, methanol, triethanolamine-buffered saline solution, and H2O2; 50 microliters) was added for a 30-minute incubation and then aspirated. Disks were air dried for visualization: solid purple dot = positive sample, or no dot = negative sample.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4026035 TI - Radiotelemetric determination of gastrointestinal pH in four healthy beagles. AB - A radiotelemetric technique for monitoring canine gastrointestinal function with clinical and research applications is described. Continuous gastrointestinal pH profiles for base-line (fasted) and postprandial states were recorded for a 6 hour test period in 4 Beagles, using a radiotelemetric device (Heidelberg capsule). Base-line gastric pH values were between 0.9 and 2.5 during the first 30 minutes, with a mean +/- SEM of 1.5 +/- 0.04. Postprandial gastric pH values varied between 0.5 and 3.5 during the first 30 minutes, with a mean of 2.1 +/- 0.04. Base-line duodenal pH values during the initial 5 minutes after gastric emptying varied from 4.5 to 7.5 with a mean of 6.1 +/- 0.1, and for the initial 60-minute post-gastric emptying, pH ranged from 4.5 to greater than 8.0 (beyond capsule calibration limit) with a mean of 6.7 +/- 0.05. The pH tended to increase linearly with time during the initial 60 minutes in the intestine. Mean gastric residence time of the capsule was 74 +/- 26.5 minutes in the fasted state (range 0 to 240 minutes). Postprandially, the capsule remained in the stomach for the duration of the 6-hour observation period. PMID- 4026036 TI - Technique for percutaneous pulmonary arterial catheterization in conscious dogs. AB - A technique was developed to allow percutaneous placement and exchange of pulmonary arterial catheters in conscious dogs. Seven dogs were catheterized weekly for 5 weeks, using a 10-gauge over-the-needle cannula. A No. 7 F flow directed catheter was passed through the cannula to measure right heart and pulmonary arterial pressures and to calculate cardiac output. The flow-directed catheter was removed and replaced with an arteriographic catheter, and a pulmonary arteriogram was performed. Placement in alternate jugular or saphenous veins each week resulted in successful catheterizations in all dogs evaluated. PMID- 4026037 TI - Changes in digital venous pressures of horses moving at the walk and trot. AB - Blood pressures from the catheterized lateral digital vein of the fore-limbs of 6 clinically normal horses were measured at rest, at the walk, and at the trot. Digital venous pressures were compared with the phases of the stride and weight bearing forces, using electrogoniometry and a force platform. Rapid increases in digital venous pressures to maximal values were observed immediately before maximal forces during the support period of the stride. At the trot, increases in peak vertical forces were paralleled by increases in peak digital venous pressures. Seemingly, the hydrodynamics of the digital circulatory system help to dissipate the initial impact of hoof strike at the walk and the trot. PMID- 4026038 TI - Changes in urea nitrogen and creatinine concentrations in the vitreous humor of cattle after death. AB - The mean urea nitrogen concentration in vitreous humor (VUN) in 97 healthy steers after death was 15.7 mg/dl. The mean serum urea nitrogen concentration in the same cattle was 20.0 mg/dl. The mean vitreous creatinine (VC) concentration was 0.7 mg/dl, and the serum creatinine value was 1.5 mg/dl. The VUN and VC were both significantly lower than serum urea nitrogen and serum creatinine, respectively, but varied in a consistent, predictable manner. In tests with 10 cows, postmortem intervals as long as 36 hours and ambient temperatures up to 30 C had no significant effects on VUN and VC. Evaluation of 8 animals with uremia confirmed that the vitreous humor is a stable fluid compartment after death, usable as an indicator of serum urea nitrogen and creatinine. PMID- 4026039 TI - Comparative efficacy of clorsulon and albendazole against Fasciola hepatica in cattle. AB - In a dosage-confirmation trial, anthelmintic activities of clorsulon and albendazole against Fasciola hepatica were evaluated and compared. Twenty-eight cattle (8 to 12 months old) with natural F hepatica infections were randomly allotted to 4 groups of 7 cattle each: group 1, no treatment (controls); group 2, clorsulon suspension given orally at 3.5 mg/kg of body weight; group 3, clorsulon suspension given orally at 7 mg/kg; and group 4, albendazole paste given orally at 10 mg/kg. At necropsies, performed 7 and 8 days after treatment, control cattle harbored a geometric mean of 133.2 F hepatica, 16.0 of which were immature. Clorsulon administered at 3.5 mg/kg or 7 mg/kg resulted in greater than 99% removal of F hepatica, including immatures. Albendazole treatment resulted in a 76% overall reduction in F hepatica, including a 91% reduction of immatures. Fascioloides magna also were found in the cattle, but neither clorsulon nor albendazole caused significant reductions of the parasite. Adverse reactions to the 2 drugs were not observed. PMID- 4026040 TI - Serum selenium concentrations and glutathione peroxidase activities in cattle grazing forages of various selenium concentrations. AB - In cows from 15 dairy herds (n = 210), serum selenium (Se) concentrations ranged from 0.021 to 0.789 microgram/ml, whereas 0.05 to 0.40 microgram/ml is the reported range for adequate serum Se concentrations in cattle. Serum Se concentrations of dairy cattle appeared to follow a geographic distribution pattern. On the basis of herd mean serum Se concentrations, adequate serum Se concentrations were found in cattle from only 1 of 5 herds grazing forage in the geographic area classified as Se deficient for cattle. Adequate mean serum Se concentrations were found in cattle from 4 of 5 herds located in geographic areas described as having variable forage Se concentrations (Se-marginal areas). Of the 10 herds from these 2 areas, there were only 2 herds in which 95% of the cattle had serum Se concentrations in the Se-adequate range (0.05 to 0.40 microgram/ml). In 2 selected neighboring farms in the Se-deficient area, cattle in 1 herd had adequate serum Se concentrations and cattle in the other herd had less than adequate serum Se concentrations (less than 0.05 microgram/ml). Therefore, more cattle are at risk of developing Se-deficiency disease than is commonly believed and forage of neighboring farms may have different Se concentrations. Serum Se concentrations (up to 0.789 microgram/ml) correlated with glutathione peroxidase enzyme activity; this serum Se concentration (0.789 microgram/ml) is approximately 6.2 times higher than previously reported in dairy cattle. Therefore, RBC glutathione peroxidase activity may be useful in determining the diagnosis of chronic Se toxicosis. PMID- 4026041 TI - Antibodies in bovine serum and lacteal secretions to capsular antigens of Staphylococcus aureus. AB - Pregnant cows were immunized systemically with an encapsulated strain of Staphylococcus aureus (Smith diffuse strain). Antibodies in serum and colostrum were detectable by enzyme-linked immunosorbent assay and prevented capsule production by the Smith diffuse strain in a soft agar medium. Antibody in milk, although detectable by enzyme-linked immunosorbent assay, did not affect the production of capsule in vitro. Antibodies were absorbed from milk and serum, using staphylococcal surface antigen. In a 2nd experiment, lactating cows were immunized, using Smith diffuse strain antigens in the form of a bacterin or as a surface extract; the bacterin or extract was emulsified in Freund's incomplete adjuvant. Antibody titers in the milk of cows given bacterin were significantly (P less than 0.001) greater than titers in the milk of animals immunized with surface extract. The soft agar technique was insufficiently sensitive to detect antibody in the milk of any of the cattle. PMID- 4026042 TI - Transmission of Anaplasma marginale by adult Dermacentor andersoni during feeding on calves. AB - Laboratory-reared Dermacentor andersoni ticks experimentally infected as nymphs with Anaplasma marginale were allowed to feed as adults from 1 to 9 days on susceptible, splenectomized calves to determine when, during feeding, the hematozoan was transmitted from ticks to cattle. In experiment 1, ticks were allowed to feed on calves for 1, 2, 3, 4, 5, or 6 days and anaplasmosis did not result. The same calves were used for experiment 2, and ticks were allowed to feed for 1, 3, 6, 7, 8, or 9 days and anaplasmosis occurred in all calves on which ticks fed for greater than or equal to 6 days. In 2 trials in experiment 3, ticks were allowed to feed on calves for 1 to 9 days. Anaplasmosis developed only in calves on which ticks fed for 7, 8, or 9 days. The prepatent periods shortened with longer tick feeding, and linear regression analysis of combined prepatent periods of both trials of experiment 3 indicated a significant (P = 0.05) slope with an estimated daily decrease of 7.75 days from day 7 to 9 of feeding. There was no apparent correlation between length of tick feeding and severity of clinical signs in those calves that developed anaplasmosis. Seemingly, A marginale can be transmitted to cattle by adult D andersoni ticks no earlier than the 6th or 7th day of feeding. PMID- 4026043 TI - Blood flow in the renal portal circulation of the turkey: effect of epinephrine. AB - Control of blood flow in the renal portal circulation of turkeys given epinephrine was evaluated by determining the distribution of injected radiopaque contrast medium within the portal circulation. Radiopacity in the region of the renal parenchyma and/or the caudal renal portal vein was increased in each of the 6 birds after epinephrine (4.0 micrograms/kg of body weight) was injected into the wing vein. In 1 bird, the contrast medium also was distributed into the mesenteric vein. Thus, epinephrine not only induced flow of blood from the pelvic limb (leg) to the kidneys, but to the abdominal viscera as well. Regulation of the patency of the renal portal valve is thought to be one means by which renal portal blood flow is controlled. However, epinephrine had no consistent effect on the valve. Thus, epinephrine seemed to control renal portal blood flow and, perhaps, blood flow to other abdominal viscera at sites other than the renal portal valve. PMID- 4026044 TI - Almitrine improves oxygenation when both awake and asleep in patients with hypoxia and carbon dioxide retention caused by chronic bronchitis and emphysema. AB - Patients with chronic bronchitis and emphysema who are hypoxic when awake become more hypoxic during sleep, with a further rise in their preexisting pulmonary hypertension. Almitrine, a respiratory stimulant, improves arterial blood gas tensions in such patients when they are awake. We have used a double-blind, placebo-controlled, cross-over study to compare the effects of 50 mg almitrine given orally twice a day for 14 days on oxygen saturation (SaO2), respiratory movements, and sleep quality in 9 patients with hypoxic chronic bronchitis and emphysema (FEV1, 0.4 to 1.0 L; PaO2, 51 +/- (SEM) 2 mmHg; PaCO2, 49 +/- 1 mmHg). Almitrine improved arterial blood gas tensions when awake, mean PaO2 rising by 8 mmHg (p less than 0.001) and PaCO2 falling by 4 mmHg (p less than 0.01). Almitrine improved nocturnal oxygenation, mean SaO2 when awake rising from 83 +/- 4% to 89 +/- 3% (p less than 0.01), and the lowest SaO2 during sleep rising on average from 65 +/- 6% to 77 +/- 3% (p less than 0.02). The number of hypoxemic episodes (SaO2 falling by greater than or equal to 10% from the preceding stable baseline during sleep) and the time when SaO2 was below 80% (135 +/- 53 versus 46 +/- 35 min; p less than 0.01) also improved. Almitrine did not improve sleep quality. We conclude that almitrine improves arterial gas tensions when awake and reduces the frequency and severity of nocturnal hypoxemia without impairing sleep quality in patients with chronic bronchitis and emphysema who are both hypoxemic and hypercapnic when awake.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4026045 TI - Pharyngeal compliance in snoring subjects with and without obstructive sleep apnea. AB - Recent studies have demonstrated a reduction in pharyngeal cross-sectional area and in upper airway muscle tone in patients with obstructive sleep apnea. These findings suggest that the pharynx in such patients may be more compliant than normal even in the awake state. We have tested this hypothesis by examining the pressure-area relationship of the pharynx in 13 patients and in 7 control subjects. Measurements were performed during wakefulness, with the subject seated, and at a constant lung volume near functional residual capacity. Pharyngeal area was measured by an acoustic reflection technique. Pharyngeal pressure was varied by having the subject perform gradual inspiratory and expiratory isovolume maneuvers against a distally occluded airway while mouth pressure was recorded. Specific compliance of the pharynx was calculated as the fractional change in pharyngeal area between a pressure of 0 and -10 cm H2O and and between 0 and 10 cm H2O. Specific pharyngeal compliance was 0.036 +/- 0.004 cm H2O-1 (mean +/- SE) in the control group and 0.094 +/- 0.012 cm H2O-1 in patients with OSA (p less than 0.01). These findings indicate that patients with obstructive sleep apnea have increased pharyngeal compliance. This abnormality predisposes to pharyngeal occlusion during sleep when negative transmural pressures are generated in the pharynx. PMID- 4026046 TI - A shift from central and mixed sleep apnea to obstructive sleep apnea resulting from low-flow oxygen. AB - Low-flow oxygen decreases the frequency of the 3 types of apnea (central, mixed, and obstructive) in patients with predominantly obstructive sleep apnea. The decrease in frequency appears to be accompanied by a shift in apnea distribution, consisting of a decrease in the proportion of central and mixed apneas and an increase in that of obstructive apneas. To determine whether this shift represents a greater inhibitory effect on central and mixed apneas or an increased tendency toward obstructive apneas, we administered low-flow oxygen during sleep to 9 patients who demonstrated predominantly central and mixed sleep apnea (51 +/- 33% and 33 +/- 21% of apneic events, respectively, mean +/- SD) and had resting, room air, oxygen tensions of 83 +/- 11 mmHg. During non-REM sleep, oxygen increased the baseline oxyhemoglobin saturation while reducing the average peak fall in oxyhemoglobin saturation during each apneic event. Oxygen reduced the overall apnea frequency from 66 +/- 7.8 (mean +/- SE) to 43.0 +/- 10.7 episodes per hour (p less than 0.02). Central and mixed apneas decreased markedly from 31.4 +/- 0.6 to 6.4 +/- 4.3 episodes per hour (p less than 0.02) and from 20.9 +/- 5.0 to 4.9 +/- 1.5 episodes per hour (p less than 0.02), respectively. However, obstructive apnea frequency more than doubled from 13.9 +/- 7.0 to 32.1 +/- 9.2 episodes per hour (p less than 0.02). We conclude that in these patients oxygen tension altered both the frequency and distribution of sleep-induced apnea, with a lower oxygen tension increasing the frequency of central and mixed apneas and a higher oxygen tension increasing the frequency of obstructive apneas.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4026047 TI - Prediction of ventilation at maximal exercise in chronic air-flow obstruction. AB - In chronic air-flow obstruction (CAO), inspiratory mechanics constitute a potential mechanism of compensation for limitation of expiratory air flow. We sought to determine whether assessment of inspiratory function could improve our ability to predict ventilation at maximal exercise (Ve max) in patients with CAO. Resting inspiratory and expiratory pulmonary function studies from 20 patients with ventilatory limitation of exercise due to CAO provided data for development of a new regression model for Ve max. Maximal exercise was quantitated from breath-by-breath analysis of exercise responses at cycle ergometry with work increments of 25 watts each min to tolerance. Multiple regression analysis by 3 methods gave identical results. A 2-variable formula containing peak inspiratory flow rate (PIFR) and the forced expiratory volume in one second (FEV1) correlated strongly with Ve max (r = 0.967) in the formula Ve max (L/min) = 21.34 FEV1 (L) + 6.28 PIFR (L/s) +3.94 (95% Cl = +/- 18 L/min). This model was significantly different from published models containing FEV1 alone (p = 0.0002) and was not improved by additional variables. Similar formulas derived for emphysematous and bronchitic clinical types of CAO did not exhibit significantly different slope and intercept coefficients. Both PIFR and FEV1 correlated strongly with tidal volume at maximal exercise. The PIFR also correlated well with resting peak inspiratory airway pressure (r = 0.775). We conclude that consideration of PIFR in addition to FEV1 can improve our clinical ability to predict Ve max in patients with CAO. PMID- 4026048 TI - Ventilatory muscle function during exercise in air and oxygen in patients with chronic air-flow limitation. AB - Ventilatory muscle function was examined at rest and during exercise on a cycle ergometer in 8 patients with moderate to severe chronic air-flow limitation (FEV1, 32 +/- 4% predicted) in air and in oxygen. The diaphragmatic electromyogram (EMG) was measured using an esophageal electrode. In addition, measurements of esophageal (Pes), gastric (Pga), and transdiaphragmatic (Pdi) pressures and abdominal wall movements were made. Patients exercised to exhaustion at a constant submaximal workload (80% of maximal power output) inspiring air or 40% O2 in random order on separate days. At end-exercise in air, tidal inspiratory Pes swings were 36 +/- 4% of static maximal inspiratory Pes, and inspiratory Pdi swings were 45 +/- 7% of the static maximal Pdi. Arterial oxygen saturation decreased from 91 +/- 2% at rest to 80 +/- 5% at end-exercise in air. During exercise in air, 5 patients demonstrated a persistent and greater than 20% fall in the ratio of high frequency (150 to 350 Hz) to low frequency (20 to 46 Hz) power (H/L) of the diaphragmatic EMG, indicating impending diaphragmatic fatigue, and 2 patients had paradoxical motion of the abdominal wall. Exercise time at the same constant work load increased from 3.0 +/- 0.6 min in air to 6.4 +/- 1.2 min in O2 (p less than 0.005). At the comparable time during exercise in O2 to end-exercise in air, minute ventilation was less by 13% (p less than 0.005), which was entirely attributable to a lower frequency of breathing. Mean inspiratory and expiratory flows and heart rate were all significantly lower.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4026049 TI - Effects of aminophylline, isoproterenol, and neostigmine on hypercapnic depression of diaphragmatic contractility. AB - We investigated the effects of aminophylline, isoproterenol, and neostigmine on decreased diaphragmatic contractility induced by hypercapnia. With the thorax open, the animal receiving mechanical ventilation, and a plaster cast around the abdomen, constant length and geometry of the diaphragm were maintained. Contractility was assessed by analysis of transdiaphragmatic pressure (Pdi) generated during supramaximal phrenic stimulation at different frequencies. Bilateral phrenectomy was performed to prevent spontaneous diaphragm movement. Hypercapnia (PaCO2, 85 mmHg) reduced Pdi by 10% at low and high frequencies of stimulation. Subsequently, aminophylline (20 mg/kg) restored Pdi to the control value at every frequency of stimulation (p less than 0.05), whereas neostigmine (0.25 and 1.0 mg) restored Pdi at low frequencies only (p less than 0.05). Isoproterenol did not improve Pdi at any frequency. Analysis of twitch characteristics revealed that hypercapnia reduced peak twitch amplitude by 17%, this being the underlying cause of the decrease in Pdi. Low and high doses of all 3 drugs significantly reversed this effect by improving peak twitch tension to values equal with or greater than control values (p less than 0.05). In addition, aminophylline (40 mg/kg) and neostigmine (0.25 and 1.0 mg) significantly increased time to peak tension of the twitch (p less than 0.05) and isoproterenol (5 and 20 micrograms/min) significantly decreased twitch half relaxation time (p less than 0.05). We conclude that aminophylline and neostigmine improve diaphragmatic contractility during hypercapnia by virtue of their potentiating effect on twitch amplitude, whereas isoproterenol does not increase contractility because the process underlying the decrease in twitch duration masks the effect of an improved twitch amplitude. PMID- 4026050 TI - The effects of chronic bronchitis and chronic air-flow obstruction on lung cell populations recovered by bronchoalveolar lavage. AB - Bronchoalveolar lavage is used to evaluate parenchymal inflammation in patients with diffuse lung disease. Normal values for lavage cell counts and proteins are derived primarily from young subjects who are free from lung disease; however, older patients who undergo bronchoalveolar lavage often have used cigarettes for long periods of time and have developed variable degrees of chronic bronchitis and/or chronic air-flow obstruction. Therefore, we evaluated the effects of cigarette use, chronic bronchitis, and chronic air-flow obstruction on lavage cell populations by performing bronchoalveolar lavage in 48 male patients who were undergoing diagnostic fiberoptic bronchoscopy. Sixteen patients (33%) had elevated percentages of neutrophils (greater than or equal to 10%) in lavage fluid. Fourteen of these (87.5%) had chronic cough and/or phlegm production, but only 9 (64.3%) met criteria for definite chronic bronchitis. Patients with moderate or severe air-flow obstruction, defined spirometrically, had significantly greater percentages of lavage neutrophils and lower percentages of macrophages than did patients with mild or no air-flow obstruction. The first lavage aliquot contained the greatest proportion of neutrophils and the smallest proportion of macrophages. The percentage of neutrophils declined and the percentage of macrophages increased in sequential aliquots. The data indicate that patients with chronic cough and/or phlegm production and chronic air-flow obstruction may have increased proportions of neutrophils in bronchoalveolar lavage fluid in the absence of diffuse parenchymal lung disease or infections. These variables must be taken into account when interpreting lavage cellular analyses.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4026051 TI - Prevalence of persistent cough and phlegm in young adults in relation to long term ambient sulfur oxide exposure. AB - In early 1976, a survey of persistent cough and phlegm (PCP) prevalence was conducted in 5,623 young adults in 4 Utah communities. Over the previous 5 years, community-specific mean sulfur dioxide levels had been 11, 18, 36, and 115 micrograms/m3. Corresponding mean suspended sulfate levels had been 5, 7, 8, and 14 micrograms/m3. No intercommunity exposure gradient of total suspended particulates or suspended nitrates was observed. In nonsmoking mothers, PCP prevalence was 4.2% in the high-exposure community and approximately 2.0% in all other communities. In smoking mothers, PCP prevalence was 21.8% in the high exposure community and approximately 15.0% elsewhere. In nonsmoking fathers, PCP prevalence was 8.0% in the high-exposure community and averaged 3.0% elsewhere. In smoking fathers, PCP prevalence was less strongly associated with ambient sulfur oxide exposure. Intercommunity prevalence differences in smoking and nonsmoking mothers, and in nonsmoking fathers, were significant at alpha = 0.05. A categorical logistic regression model, testing simultaneously for effects of community and several covariates on PCP prevalence, yielded similar results. The results of this survey were similar to those of a similar survey conducted in Utah in 1970 and to those of other surveys. These results disclose an association of PCP prevalence with ambient sulfur oxide exposure, stronger in mothers than in fathers, stronger in nonsmokers and ex-smokers than in smokers, and stronger in 1970 than 1976. PMID- 4026052 TI - How many spirograms for a histamine challenge? AB - Several reports have shown that a prior deep inspiration exerts a blunting effect on pharmacologically induced bronchoconstriction. Inspiration to total lung capacity is a mandatory requirement for valid determination of the FEV1, and thus, the FEV1 may underestimate the magnitude of induced airway obstruction. The present study was designed to assess the effect that the performance and separate analysis of 2 consecutive FEV1 maneuvers (FEV(1)1, FEV(1)2), obtained at different levels of histamine-induced bronchoconstriction, may have on the final interpretation of a histamine challenge. Eight asymptomatic nonsmoking asthmatics (mean age, 24 yr; range, 19 to 27 yr) underwent a total of 16 histamine challenges. Paired FEV1 measurements (FEV(1)1, FEV(1)2) were obtained after inhalation of buffer solution (control) and 3 min after inhalation of aerosolized, serially diluted, histamine diphosphate solutions. A significant airways response (FEV1 decreasing by 20% or more from the control value) was observed in all subjects after inhalation of 5 mg/ml of histamine or less, indicating histamine airway hypersensitivity. At lower doses of histamine the mean values for FEV(1)1 and FEV(1)2 were similar to the control value. At higher histamine doses FEV(1)2 was consistently higher than FEV(1)1 (p = 0.007) and exceeded FEV1 1 by a mean of 9% after inhalation of the provocational histamine concentration; delta FEV1(FEV(1)2-FEV(1)1) was correlated with the log10 of cumulative inhaled histamine dose units (p = 0.040). Assuming that the difference between corresponding FEV1 determinations at a given level of induced bronchoconstriction is a direct consequence of changes in lung mechanics induced by deep inspiration, we are led to conclude that during histamine inhalation challenges, only 1 spirogram should be performed at each level of induced bronchoconstriction. PMID- 4026053 TI - Histamine-induced reflex tracheal constriction is attenuated by hyperoxia and exaggerated by hypoxia. AB - The effect of vagal reflexes on bronchomotor tone can be altered by their interaction with other bronchomotor factors, such as the prevailing state of oxygenation. In anesthetized, paralyzed, and artificially ventilated dogs, a reflex constriction was induced in an isolated tracheal segment by administration of aerosolized histamine to the lungs. When the challenge was repeated during hypoxic conditions (PaO2, 45 mmHg), the magnitude of the reflex response was significantly larger than during normoxia. In contrast, during hyperoxia (PaO2, 344 mmHg), the response was significantly smaller than the normoxic response. The changes in the prevailing state of oxygenation were done under isocapnic and isohydric conditions. Hyperoxia alone had no effect upon baseline bronchomotor tone, whereas hypoxia caused an increase in baseline tone in approximately half the animals. The effect of hypoxia upon the reflex response to histamine was not affected by the baseline changes. We think that the potentiating effects of hypoxia and the attenuating effects of hyperoxia are mediated by an interaction between lung sensory receptors and carotid body chemoreceptors. PMID- 4026054 TI - Influence of alveolar oxygen on pulmonary vasoconstriction in newborn lambs versus sheep. AB - Fetal lung has vigorous hypoxic vasoconstriction and is exposed continuously to an O2 tension less than 20 mmHG, which is well below that experienced by adult lungs. We wondered if the newborn lamb, with muscular arteries similar to the fetus, might not have a different O2 tension for developing alveolar hypoxic vasoconstriction in addition to having stronger vasoconstriction than the less muscular adult lung. Therefore, regional hypoxic pulmonary vasoconstriction in newborn lambs (mean of 5 days) and adult sheep (older than 2 yr) was compared at graded levels of alveolar oxygen tension. Animals were anesthetized with pentobarbital, and each main bronchus was cannulated to allow ventilation of one lung with N2 or other O2/N2 mixtures as a "hypoxic" challenge while ventilation of the other lung with O2 maintained systemic oxygenation. Distribution of perfusion to the 2 lungs during bilateral O2 ventilation was first determined with 13N and a positron camera. The lambs significantly (p less than 0.05) decreased the distribution of perfusion to the test lung compared with O2 control (PAO2, 620 +/- 15) by 44 +/- 1% SEM with PAO2 of 22 +/- 1 mmHg, 22 +/- 3% with PAO2 of 96 +/- 1 mmHg, and 12 +/- 2% with PAO2 of 360 +/- 3 mmHg in contrast to the sheep that significantly decreased the distribution of perfusion to the test lung compared with O2 control distribution of perfusion by only 22% at a PAO2 of 19 +/- 2 mmHg and not at higher alveolar O2 tensions.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4026055 TI - Determinants of hypoxemia during the acute phase of pulmonary embolism in humans. AB - The determinants of hypoxemia were studied in 10 patients with acute pulmonary embolism demonstrated by pulmonary angiography. Two patients were mechanically ventilated, and in the 8 who breathed room air spontaneously, the mean arterial PO2 was 61.5 mmHg. Measurements of the distributions of ventilation (VA) and perfusion (Q) against VA/Q ratios by the multiple inert gas infusion technique demonstrated an increase in VA/Q inequality. The major part of pulmonary blood flow was distributed in a mode near to, or slightly above, a VA/Q ratio of 1. The cumulative fraction of blood in true shunt and low VA/Q mode (VA/Q less than 0.01) was 9.1%. For a small part of the AaDO2 (13%), an oxygen diffusional component was found. The remaining hypoxemia was due to the fall in the mixed venous PO2 (PVO2), irrespective of its cause: low cardiac output, low hemoglobin concentration, high oxygen consumption, low P50. The fall in PVO2 led to a fall in end-capillary blood PO2 in both shunt or ventilated and perfused units. We conclude that the major determinant of hypoxemia in these patients suffering from acute pulmonary embolism is the fall in PVO2. This is enhanced by a moderate increase in the fraction of blood flowing through low VA/Q units. Diffusion impairment plays only a minor role. PMID- 4026056 TI - The effect of a gas leak around the endotracheal tube on the mean tracheal pressure during mechanical ventilation. AB - Infants requiring mechanical ventilation are usually intubated with uncuffed endotracheal tubes, which permit gas to leak between the tube and the trachea. This gas leak may alter the mean pressure transmitted to the trachea by changing the pattern of airway flow and modifying the resistive behavior of the endotracheal tube. To test this hypothesis, we measured mean tracheal pressure, gas flow through the endotracheal tube, and resistance of the tube in rabbits ventilated with and without a leak. We also studied the effect of the tube size and the pattern of ventilation on these measurements. We found that a leak reduced the mean tracheal pressure by 15 to 21% with respect to the mean proximal airway pressure. This reduction was caused by an increased difference between inspiratory and expiratory flow through the endotracheal tube, and by the mean expiratory resistance of the tube being lower than its mean inspiratory resistance. The rabbits with smaller tubes had lower mean tracheal pressures. A ventilatory pattern of short inspiratory times and high peak pressures was associated with a proportionally greater decrease in mean tracheal pressure caused by the leak. These findings suggest that the mean proximal airway pressure, measured at the ventilator, may overestimate the mean tracheal pressure in the presence of a gas leak around the tube. Furthermore, the decrease in mean tracheal pressure caused by the leak may decrease oxygenation despite a constant mean proximal airway pressure. PMID- 4026057 TI - Alveolar pressure magnitude and asynchrony during high-frequency oscillations of excised rabbit lungs. AB - One possible advantage of high-frequency ventilation (HFV) over conventional mechanical ventilation is that adequate pulmonary ventilation may be established with lower pressure swings. Pressure swings measured at the airway opening may not accurately reflect pressure swings in the alveoli, however. Furthermore, little is known about the synchrony of alveolar filling during HFV. We have assessed the magnitude of alveolar pressure swings (PA) relative to those at the airway opening (Pao) and investigated asynchrony of alveolar filling during small tidal volume (less than 1.0 ml), high-frequency (1 to 60 Hz) oscillations (HFO) in 8 excised rabbit lungs. The PA was measured in several capsules glued to the pleural surface and communicating with alveolar gas via pleural punctures. The peak value of the ratio [PA/Pao] occurred near the resonant frequency and was 1.90, 1.45, and 1.0 at distending pressures of 25, 10, and 5 cm H2O, respectively. Temporal asynchrony of PA between sampled lung regions was quantified by measuring the interregional standard deviation of alveolar pressure phase angles, delta phi. The delta phi increased with increasing frequency and decreasing transpulmonary pressure. The maximal observed delta phi was 30 degrees. These results, when compared with earlier results on excised canine lungs, show that the amplification of PA during HFO is lung-size dependent. The observed degree of phase differences in pressure swings between peripheral alveolar locations implies substantial asynchrony of alveolar filling. This in turn suggests interregional gas transport as an important contributor to gas mixing during HFV. PMID- 4026058 TI - Nitrogen washout during tidal breathing with superimposed high-frequency chest wall oscillation. AB - In order to assess the efficacy of high-frequency chest wall oscillation (HFCWO) superimposed on tidal ventilation, multiple-breath nitrogen washout curves were obtained in 7 normal seated subjects. To maintain a regular breathing pattern throughout the study, the subjects breathed synchronously with a Harvard ventilator set at a constant tidal volume and frequency for each subject during a trial period. Washout curves were obtained during 3 different maneuvers performed in random order. Series A was the control condition with no superimposed HFCWO. In Series B and C, HFCWO at 5 Hz was superimposed on the regulated tidal breathing; the magnitude of the oscillatory tidal volume measured at the airway opening was 20 ml for Series B and 40 ml for Series C. The nitrogen washout was clearly faster in Series C than in Series A for each subject. In Series B, there was an interindividual variability, with a washout rate either equal to that in Maneuver A or in Maneuver C, or intermediate between the two. When these washout curves were analyzed in terms of a simple monocompartment model, the time constant of the washout was found to decrease by 16 +/- 11% in Series B, and 25 +/- 7% in Series C compared with that in Series A. In this group of normal subjects, the correction of any inhomogeneity in the distribution of the ventilation is unlikely to explain these results because of the close fit of all washout curves to a monoexponential model. It is postulated that during inspiration HFCWO enhances gas mixing in the lung periphery and that during expiration it improves gas mixing in the airways.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4026059 TI - Hyperoxic lung injury and polyamine biosynthesis. Age-related differences. AB - To determine if lung cell replication and repair might be different between younger (30-day-old) and older (60-day-old) rats, we studied polyamine and DNA biosynthesis in rats exposed to 1.0 atm oxygen for 24, 48, 56, or 72 h. By 24 h, no statistically significant changes were observed, but by 48 h, ornithine decarboxylase and putrescine increased; S-adenosylmethionine decarboxylase activity increased by 56 h in the younger rats but not in the older rats. By 72 h, spermidine, [3H]thymidine incorporation, and the labeling index of cells in the alveolar zone had increased only in the younger rats. During the first 56 h, hyperoxia inhibited DNA synthesis. We conclude that hyperoxia initially suppresses lung cell replication but subsequently, if the rat survives, there are increases in polyamine biosynthesis and cell replication that may be important for the development of oxygen tolerance. PMID- 4026060 TI - Dissemination of Pseudomonas aeruginosa during lung infection in hamsters. Role of oxygen-induced lung injury. AB - Pseudomonas aeruginosa was inoculated into the lungs of normal and oxygen-exposed hamsters. Air-breathing animals developed focal bronchopneumonias but viable organisms were not recovered from the lungs after 3 days; bacteremia was not detected but P. aeruginosa was isolated from the livers of 3 of 12 animals with positive lung cultures. Pseudomonas aeruginosa infection shortened the survival time of oxygen-breathing hamsters, and organisms persisted in the lungs during oxygen exposure. Focal bronchopneumonias were uncommon in animals inoculated after 4 days of oxygen exposure; the predominant histopathologic finding was accentuation of diffuse alveolar damage and increased numbers of scattered neutrophils. Pseudomonas aeruginosa was recovered from the livers of 15 of 18 oxygen-exposed animals in which lung colony counts exceeded 10(3)/lung; only 8 of these animals had demonstrable bacteremia. The concentration of elongation factor 2 in the livers and lungs of oxygen-exposed animals was reduced as colony counts of P. aeruginosa increased in the lungs of infected animals, suggesting exotoxin A activity in these organisms. These findings suggest that bacterial superinfection of injured lungs may account for both worsening lung function and impaired function of other organs. PMID- 4026061 TI - Choosing an appropriate cutting point for conversion in annual tuberculin skin testing. AB - A previous report from our institution showed that the use of a two-step tuberculin testing program in new employees reduced the apparent rate of conversion in annual skin testing by eliminating the effect of the booster phenomenon. However, the converter rate subsequently remained too high. We propose that the use of 10 mm of induration as the cutting point gave a high rate of false conversion in our area of high prevalence of sensitivity to nontuberculous mycobacteria. A change to 15 mm of duration as the cutting point reduced our conversion rate from 2.6 to 1.2%, identified a group who demonstrated continued large tuberculin reactions at repeat testing, and eliminated age dependency from our converter population. We propose the choice of 15 mm of induration as the appropriate cutting point in annual employee tuberculin skin testing programs in areas in which sensitivity to nontuberculous mycobacteria is common. PMID- 4026062 TI - Phage typing of the Mycobacterium avium-intracellulare-scrofulaceum complex. A study of strains of diverse geographic and host origin. AB - A total of 339 strains of the Mycobacterium avium-intracellulare-scrofulaceum complex were phage typed using our previously described technique and 11 typing phages. These included 235 strains of human origin obtained from state health laboratories in Virginia, Georgia, Florida, and Arkansas, 26 strains isolated from persons with AIDS, 38 strains isolated from animals, and 40 environmental isolates. A phage-typing scheme was developed that denotes sensitivity to 8 primary typing phages: the JF group (JF1, JF2, JF3, and JF4), phage D302, and the AN group (AN3, AN9, and AN1-8). The 3 auxiliary phages (VC3, VA6, and D32) define subgroups of the strains sensitive to the AN phages. A total of 99 strains were sensitive to at least 1 phage. Of 31 serotype 1 or 2 strains from animals, 13 were sensitive to AN phages but resistant to JF phages. In contrast, 7/33 serotype 4 or 8 strains from animals or from persons with AIDS were sensitive to JF phages but not to the AN phages. Of the clinical isolates not associated with AIDS, 78/235 were phage sensitive. These strains could be divided roughly into 4 groups: sensitive to AN phages, sensitive to JF phages, sensitive to phage D302, and sensitive to multiple phages. Only 1 of the environmental isolates was phage sensitive. The results indicate that phage typing can subdivide this heterogeneous group of organisms and is a useful tool for epidemiological studies. PMID- 4026063 TI - Effect of changing instilled volume for bronchoalveolar lavage in patients with interstitial lung disease. AB - Patients with and without interstitial lung disease (ILD) underwent bronchoalveolar lavage (BAL) with 4 boluses of 60 ml of normal saline. Fluid was withdrawn after each bolus, and the results after the first and second bolus were pooled and compared with the results after the third and fourth bolus. In the control group (n = 9), there was a significantly higher percentage of lymphocytes and neutrophils after the first half than after the second half (first half: lymphocytes, 8 +/- 1.9%, mean +/- SEM; neutrophils, 2 +/- 1.2%. Second half: lymphocytes, 5 +/- 1.2% (p less than 0.01); neutrophils, 0.3 +/- 0.12% (p less than 0.05). In the ILD group (n = 8), there was a rise in the number of lymphocytes from 15 +/- 4.9% to 20 +/- 3.9% (p less than 0.05) and the number of neutrophils from 8 +/- 4.8% to 10 +/- 5.6%. The ILD group had more cells aspirated after the second half than after the first half of the BAL, whereas the control group did not. Abnormalities in the cell population of the BAL fluid were more striking when the larger volume was used. PMID- 4026064 TI - Mineral dust and cell recovery from the bronchoalveolar lavage of healthy Vermont granite workers. AB - We characterized the bronchoalveolar lavage (BAL) from healthy Vermont granite workers to investigate the pulmonary response to a chronic exposure to an injurious agent. Nine granite workers with 4 to 36 yr of employment in the industry and 27 unexposed volunteers were normal by history, physical examination, electrocardiogram, blood count, spirometry, and chest radiograph. Lavage cell recovery and percent neutrophils were not different. Lymphocyte recovery in BAL was increased in the granite-exposed population. Granite dust was present within the majority of alveolar macrophages from granite workers compared with those from control subjects, as determined by polarizing light microscopy and confirmed by scanning electron microscopy with X-ray energy spectrometry. There were no differences in phagocytic function or viability of macrophages from granite workers compared with those from unexposed volunteers. We conclude that in exposed populations, granite dust can be detected and semiquantitated in lavage specimens within the alveolar macrophages, macrophage function is preserved, and the response to this exposure involves an influx of lymphocytes. PMID- 4026065 TI - Mutational resistance as the mechanism of acquired drug resistance to aminoglycosides and antibacterial agents in Mycobacterium fortuitum and Mycobacterium chelonei. Evidence is based on plasmid analysis, mutational frequencies, and aminoglycoside-modifying enzyme assays. AB - Possible mechanisms of drug resistance of Mycobacterium fortuitum and Mycobacterium chelonei to antibacterial agents were investigated. Single-step mutational frequencies were low (generally less than or equal to 10(-7] for cefoxitin, doxycycline, erythromycin, and sulfamethoxazole and relatively high (10(-4) to 10(-7] for kanamycin and amikacin. Aminoglycoside-susceptible strains of both species contained an aminoglycoside acetyltransferase (3)-III or IV. No additional enzymes were seen with laboratory or clinically acquired aminoglycoside resistance. Plasmids of several sizes were present in some susceptible isolates of both species, but acquired resistance was not associated with a change in the apparent size or number of these plasmids. Isolates with acquired resistance to amikacin were resistant to the other 2-deoxystreptamine aminoglycosides but showed little or no change in minimal inhibitory concentrations to streptomycin, suggesting either a difference in cellular uptake between the 2 groups of drugs or, more likely, different binding sites on the ribosome. In 59 patients treated with 63 courses of therapy with a single agent for 1 month or longer, the development of resistance was observed only twice (3%). Both isolates had high mutational frequencies (10(-4) and 10(-5]. These studies support mutational resistance as the mechanism of acquired resistance to antibacterial agents in M. fortuitum and M. chelonei. PMID- 4026066 TI - Bronchogenic carcinoma in the elderly. PMID- 4026067 TI - Postsplenectomy complications. AB - Postsplenectomy complications were reviewed among 420 patients with simple splenic injury, splenic plus multisystem trauma, elective splenectomy, incidental or accidental splenectomy, and those having splenectomy prior to renal transplantation. Complications not specifically related to splenectomy occurred postoperatively in 52 per cent and 41 per cent, respectively, in the complex trauma and incidental-accidental splenectomy groups. Nonfatal complications specifically related to splenectomy occurred in 15 per cent of patients with multi-organ injury and in 18 per cent of patients with incidental-accidental splenic removal. Morbidity was infrequent when simple splenic trauma prompted splenectomy or in elective splenectomy. Mortality related to splenectomy occurred most often following renal transplantation, but also appeared high when the spleen was removed for multiple trauma or incidental to other surgery. The latter category is at risk for morbidity and mortality when splenectomy is incidental to a planned procedure (e.g., radical gastrectomy) or accidental as when injured by the surgeon. These splenectomies and those planned prior to transplantation may be unnecessary in many instances. The postsplenectomy sepsis syndrome was encountered late only once in this entire series; nonetheless, sound indications for splenectomy must prevail before splenic removal since significant early morbidity and mortality follows splenectomy. PMID- 4026069 TI - Identification of factors responsible for wound infection following allograft nephrectomy. AB - The advisability of routine allograft nephrectomy following rejection has not been clearly resolved. Rejected transplants may be a source of sepsis, local inflammatory symptoms, and continued antigenic stimulation. Transplant nephrectomy is, however, attended by a surprisingly high incidence of septic complications and death. In an attempt to analyze the occurrence of these, and identify effective prophylactic maneuvers, the authors retrospectively studied 99 consecutive allograft nephrectomies in 252 consecutive renal transplants. Mortality following allograft nephrectomy was 10 per cent, and usually attributable to sepsis. Wound infections occurred in 24 per cent of these patients and were significantly associated with a preoperative site of infection in the wound, urinary tract, or blood (P less than 0.01). Preoperative antibiotics, wound irrigation, drains, and delay in performing allograft nephrectomy were all found to be insignificant variables. Interestingly, total steroid dose was less in patients who developed wound infections than in those who did not (P less than 0.01). A postoperative wound infection approximately doubled the mean number of hospital days. These data suggest that a significant reduction in morbidity and possibly mortality could be accomplished by complete eradication of infection prior to allograft nephrectomy. Consequent delay in removal of the graft is not associated with increased morbidity, and other maneuvers seem to have little beneficial effect. PMID- 4026068 TI - Correlation of immune and nutritional status with wound complications in patients undergoing abdominal surgery. AB - The present study indicates the need for close scrutiny of the immune and nutritional status of patients undergoing abdominal surgery. Simple anthropometric measurements (weight and triceps skin fold thickness MAC) serologic testing (serum albumin), ALC, and skin testing are useful to identify patients with immunocompromise caused by nutritional deficiency. Early recognition and correction of immune nutritional deficits in patients undergoing abdominal surgery should lead to reduction in postoperative morbidity due to wound complication. PMID- 4026070 TI - Lipoma of the colon. A report of 22 cases. AB - A series of 22 cases of lipomas of the colon is presented. Fourteen patients had small (mean size, 12.5 mm), asymptomatic colon lipomas which were diagnosed incidently. In four of these patients, more than one lipoma was found. Eight patients had one larger (mean size, 70.5 mm) symptomatic lipoma. The symptomatic patients were older (mean age, 64.3 years) than the asymptomatic patients (mean age, 54.7 years). While small lipomas do not generally give symptoms, it seems that the symptoms of larger lipomas are mainly due to mechanical interference in colonic passage or ulceration of the mucosa that covers the lipoma. PMID- 4026071 TI - Cystic adventitial disease of the popliteal artery. AB - Cystic adventitial disease of the popliteal artery has been recognized as a cause of arterial stenosis and calf claudication for 30 years. It is reported infrequently and its etiology remains unknown. In addition, a peculiar geographic distribution of the reported cases of this disorder has been noted, with a majority of cases from Europe and Australasia. The authors report here a case from South Carolina in which a fibrous band may have contributed to compression during exercise. Noninvasive studies and angiographic studies were negative before exercise and positive after exercise. Current ideas of diagnosis, surgical treatment and possible etiology are presented. PMID- 4026072 TI - Unsuccessful control of abdominal aortic aneurysm by bypass and ligation. AB - Two patients developed abdominal aortic aneurysm rupture following bilateral iliac artery ligation and axillobifemoral bypass. The first patient developed his rupture several weeks after outflow ligation and apparent thrombosis of the aneurysm. At autopsy, the aneurysmal rupture occurred in the left posterior junction between the thrombosed aneurysm and the normal aorta. In the second case, the aneurysm was not completely thrombosed and plans were in progress for thrombosis of the aneurysm when the patient developed frank rupture, necessitating operative intervention. The authors await the published experience of others with bilateral common iliac artery ligation and extra-anatomic bypass for abdominal aortic aneurysm, but these authors do not currently recommend this management plan. PMID- 4026073 TI - A survey of technical considerations in the construction of intestinal stomas. AB - Reported complications rates for the construction of intestinal stomas are high. Many of these complications result from improper construction, improper location, or other technical errors. In order to sample the techniques of stoma construction currently in use, a survey was conducted at the 69th Annual Clinical Congress of the American College of Surgeons in Atlanta in conjunction with our scientific exhibit "Complications of Intestinal Stomas." A total of 245 surgeons completed the questionnaire with a mean age of 47.8 years. The routine use of fascial-seromuscular tacking sutures and primary maturation of a loop colostomy in the presence of distal obstruction were among the most controversial technical points considered. Many other subtle but important principles of stoma construction were also discussed. In addition, the authors contend that many of the techniques currently in use result from an underemphasis on the importance of proper stoma construction in many surgical training programs. PMID- 4026074 TI - Comparison of needle catheter versus standard tube jejunostomy. AB - It is commonly stated that needle catheter jejunostomy (NCJ) is associated with fewer complications than standard tube jejunostomy (STJ). We compared the morbidity of NCJ versus STJ performed as adjunctive procedures in 90 patients from 1977 to 1983. NCJ was performed in 55 patients and STJ in 35 patients. The two groups were similar with respect to age, sex, diagnosis, and operation performed. The overall postoperative morbidity was 35 per cent for the NCJ group and 62 per cent for the STJ group. Mortality was 19 per cent and 35 per cent, respectively. Minor complications related to the jejunostomy occurred in 16 per cent of the NCJ group and 9 per cent of the STJ group. Diarrhea and abdominal distention occurred with equal frequency in the two groups. One NCJ patient required reoperation for intestinal obstruction at the catheter exit site, and one STJ patient required operative closure of a fistula following tube removal for major complications rates of 1.8 per cent and 2.8 per cent, respectively. The statement that STJ is associated with more jejunostomy-related complications than NCJ is not substantiated by this study. Because of greater ease of insertion, NCJ remains our procedure of choice for adjunctive feeding jejunostomy. PMID- 4026075 TI - Small bowel obstruction in the elderly. AB - Hospital records were reviewed for all patients 70 years or older who were treated for small bowel obstruction (SBO) at The New York Hospital-Cornell Medical Center from January 1975 through December 1980. There were 87 patients treated surgically and 20 patients treated nonoperatively. When the clinical evidence of strangulation was evaluated for preoperative reliability, 35 per cent of the patients had none of the accepted criteria for strangulation. Complications occurred in 60.9 per cent of patients following operative intervention. Wound infection was the most common postoperative complication and was related to wound management and to the number of enterotomies made at the time of surgery. Using delayed 1 degree closure, the infection rate was 6.2 per cent compared to 21.1 per cent when wounds were closed at surgery. The overall operative mortality was 18 per cent; advanced carcinoma accounted for 60 per cent of these fatalities. The mortality for patients with nonmalignant obstruction was 10.0 per cent as compared with 40.7 per cent in patients with cancer. From these data the authors conclude: that age alone should not be a deterrent to operative intervention in small bowel obstruction; the presence of a 1 degree or 2 degrees malignant process in the elderly patient is a significant risk factor for mortality; any patient operated on for SBO having an enterotomy should have their wound managed by delayed 1 degree closure; and because of the lack of reliability of the clinical criteria for strangulation, operative intervention in the elderly should be undertaken as soon as the diagnosis of mechanical obstruction is made. PMID- 4026077 TI - Elevated pulmonary vascular resistance in patients dying from multiple organ failure. AB - Twenty-one patients with multiple organ failure were studied with hemodynamic monitoring. The five survivors were compared with the 16 nonsurvivors. Significant differences were found in the cardiac index (CI), the left ventricular stroke work index (LVSWI), and the pulmonary vascular resistance index (PVRI). The CI was higher in survivors (4.38 +/- 1.71) than in nonsurvivors (3.43 +/- 1.49). The LVSWI was also higher (43.0 +/- 16.8, 28.7 +/- 12.8) than in nonsurvivors (47.4 +/- 2.91). The PVRI was lower in survivors (168 +/- 122) than in nonsurvivors (474 +/- 291). It is postulated that the elevated PVRI in MOF is related to the adult respiratory distress syndrome. PMID- 4026076 TI - The use of barium enema in the evaluation of patients with possible appendicitis. AB - Patients with right lower quadrant pain and possible appendicitis may present a difficult diagnostic dilemma to the surgeon. Barium enema has been used as an adjunctive test in the evaluation of patients with right lower quadrant pain in whom the diagnosis is unclear. The authors retrospectively reviewed their experience with 33 patients to determine the value of barium enema. The average age was 32 years (range, 2-89 years). Twenty-five patients had nonfilling of the appendix; nine of these patients had a mass effect on the cecum. Three patients had partial filling of the appendix and five patients had a normally filled appendix. Of the 16 patients who had nonfilling of the appendix without a filling defect of the cecum, 14 patients underwent operation. Eleven patients had appendicitis and three patients had a normal appendix. Two patients with nonfilling did not undergo operation and did well. All patients with a filling defect of the cecum on barium enema had appendicitis. All patients with partial filling of the appendix had appendicitis. Of five patients with normal appendices on barium enema, one patient had a diverticular abscess and underwent operation, and another patient had Meckel's diverticulitis which was excised. Barium enema can provide information to aid in the management of patients in whom the diagnosis of appendicitis is not clear. It can prevent unnecessary operation in some, and assist in earlier operation in others. PMID- 4026078 TI - Report of two patients with hypertrophic pyloric stenosis and Hirschsprung's disease. Coincident or common etiology? AB - Although the etiologies of Hirschsprung's disease and infantile hypertrophic pyloric stenosis remain unclear, it is certain that in Hirschsprung's disease, there is an absence of myenteric ganglia. In pyloric stenosis, there is a decreased number of ganglia, but this may be secondary phenomenon. The occurrence of both Hirschsprung's disease and pyloric stenosis in any single patient is uncommon, disputing a common etiology on statistical grounds. The authors have recently seen two infants with both diseases, and have reviewed the histology and pathophysiology analyzing the possibility of a single cause. PMID- 4026079 TI - Interstitial radiation implantation for unresectable nonoat cell carcinoma of the lung. Techniques and preliminary results. AB - The majority of lung cancers are unresectable at diagnosis. The radiation tolerance of the surrounding spinal cord and heart limits the external radiation therapy dose. Interstitial radiation implantation was utilized to deliver higher radiation dose, sparing the surrounding normal tissues in patients with unresectable nonoat cell cancers of the lung less than 8 cm in diameter localized to the thorax with no associated pleural effusion. The methods of implantation included permanent interstitial iodine-125 implantation of the gross disease in the lung and/or lymph nodes delivering about 120 Gy (12,000 rads) in 1 year and removable iridium-192 interstitial implantation of residual disease in the mediastinum, chest wall, or margin or resection in the lung, delivering about 30 Gy (3000 rads) in three days. Supplementary external radiation therapy of 40 Gy (4000 rads) in 4 weeks is delivered 4-6 weeks after implantation. The interstitial implant procedure adds only about 45 minutes to 1 hour to the operating time, and converts a palliative procedure into a potentially curative treatment. This article presents our experience with 11 cases, with early short term follow-up results, and is designed to stimulate others to evaluate a similar approach to improve local control and survival in unresectable lung cancers. PMID- 4026080 TI - Pathologic blood flow in pulmonary vascular disease as shown by gated magnetic resonance imaging. AB - Axial, dual spin-echo magnetic resonance (MR) images, taken at the level of the pulmonary arteries and gated to the cardiac cycle, were qualitatively and quantitatively evaluated in nine patients with primary pulmonary arterial hypertension and six controls. In controls and patients, intravascular signal intensity was higher during diastole than during systole when fast flow conditions exist in the arteries; however, patients with severe pulmonary arterial hypertension showed significantly higher signals in the pulmonary arteries than did controls. A correlation between pulmonary vascular resistance and the MR signal in the right pulmonary artery in early systole (r = 0.89) showed the ability of MR images to provide information on blood flow and suggests a role for magnetic resonance in assessing the severity of this disease noninvasively. Flow-related cardiosynchronous variations in the lung parenchyma of controls were also observed; with further development, magnetic resonance may become useful to measure tissue perfusion and provide both pathoanatomic and pathophysiologic information. Furthermore, there was a significant difference between the MR signal intensity of dorsal and ventral lung regions. PMID- 4026081 TI - Primary myeloproliferative disorder and hepatic vein thrombosis. A prospective study of erythroid colony formation in vitro in 20 patients with Budd-Chiari syndrome. AB - We assessed the prevalence of overt and latent primary myeloproliferative disorders in hepatic vein thrombosis. Cultures of bone marrow or peripheral blood mononuclear cells were done in 20 patients with Budd-Chiari syndrome. Erythroid colony formation in the absence of erythropoietin, which is a reliable indicator for a primary myeloproliferative disorder, was seen in 16 patients in whom Budd Chiari syndrome was due to hepatic vein thrombosis, including 13 women aged 18 to 45 years. Among these 16 patients, the conventional criteria for the diagnosis of a primary myeloproliferative disorder were met in only 2. Primary myeloproliferative disorder, often without peripheral blood changes, is a major cause of hepatic vein thrombosis in young women. PMID- 4026083 TI - Smoking and age at menopause in women. AB - Although women can expect to live one half of their adult lives beyond menopause, knowledge about this physiologic event and its various influences on subsequent health and quality of life remains incomplete. In Massachusetts we studied a population-based random sample of 7828 white women, aged 45 to 55 years (response rate, 77%). The median age at last menstruation for the sample is 51.4 +/- 0.19 (SE) years years, and we found no evidence of a secular trend towards a later age at menopause in the last 25 years. Current smokers reach menopause an average of 1.74 years earlier than nonsmokers (t = 3.78, p less than 0.01), but the quantity smoked has a negligible effect. Other potential correlates measured--education and marital status, number of children, and urban/rural residence--have little effect on the age at menopause. The results confirm earlier, more tentative findings from clinical populations. PMID- 4026082 TI - Vinblastine therapy for Kaposi's sarcoma in the acquired immunodeficiency syndrome. AB - Single-agent intravenous vinblastine, 4 to 8 mg/week, was used to treat 38 patients with Kaposi's sarcoma related to the acquired immunodeficiency syndrome. The dose was titrated in relation to the total leukocyte count. Ten patients had an objective response, and 19 had stable disease during therapy. Apart from expected modest neutropenia, toxicity was minimal. A lower response rate was seen in patients with anemia, an elevated erythrocyte sedimentation rate, or any lymphoma-like B symptom. Opportunistic infections were common regardless of type of response but were commoner in patients who did not respond. Vinblastine used in low doses weekly is effective in treating Kaposi's sarcoma related to the acquired immunodeficiency syndrome and has minimal associated toxicities. PMID- 4026084 TI - Polyarthritis and neutropenia associated with circulating large granular lymphocytes. AB - Five patients with polyarthritis and neutropenia had numerous circulating large granular lymphocytes with a phenotype attributed to immature natural killer cells. All five had splenomegaly and recurrent infections. Arthritis was most prominent at the wrists and hands, and all patients were considered to have atypical cases of Felty's syndrome. Antinuclear antibodies, rheumatoid factor, antineutrophil antibodies, and immune complexes were detected in most patients. Bone marrow biopsies revealed a maturation arrest at the myelocyte stage and lymphoid infiltrates. Large lymphocytes with azurophilic cytoplasmic granules were found on peripheral blood smears and showed a characteristic reactivity pattern with monoclonal antibodies suggesting a natural killer cell lineage. Peripheral blood mononuclear cells showed less than normal natural killer activity against K562 target cells. Increased numbers of large granular lymphocytes with a phenotype of immature natural killer cells may be important in the pathogenesis of neutropenia, humoral immune disturbances, and synovitis in a subset of patients with Felty's syndrome. PMID- 4026085 TI - Unilateral blindness caused by infection with the Lyme disease spirochete, Borrelia burgdorferi. PMID- 4026087 TI - The academic viability of general internal medicine. The views of department of medicine chairmen. AB - A national survey of department of medicine chairmen was conducted to learn their views of the status of academic general internal medicine. Developing a research program in general internal medicine was considered a high priority by 60% of the department chairmen at the time their general internal medicine divisions were established, and by 1981, 83% considered this a high priority. However, only 17% stated that significant progress had been made by the division at their institutions toward achieving this goal. Chairmen identified problems with funding for research, their faculty's ability to do research, and available time of faculty to conduct research. They stated their intention to assist the division of general internal medicine in developing a research program through financial and organizational support. At least two thirds planned to recruit selectively general internal medicine faculty who had research backgrounds and interests and to require the existing faculty to do research as a condition for continued appointment. PMID- 4026086 TI - Zinc-induced copper deficiency: megamineral sideroblastic anemia. PMID- 4026088 TI - Nosocomial hepatitis A. PMID- 4026089 TI - The GPEP report: III. Faculty involvement. PMID- 4026090 TI - Divisions of general internal medicine: accomplishments and needs. PMID- 4026091 TI - Serologic testing for Lyme disease. PMID- 4026092 TI - Difficulties in assessing dementia. PMID- 4026093 TI - Peer review. PMID- 4026094 TI - HLA antigens in angioimmunoblastic lymphadenopathy. PMID- 4026095 TI - Duodenal perforation by an infusion catheter for hepatic chemotherapy. PMID- 4026096 TI - Drug extravasation and the Port-a-Cath system. PMID- 4026097 TI - Antineoplastic drugs as an occupational hazard in hospitals. PMID- 4026098 TI - Erythromelalgia without thrombocythemia. PMID- 4026099 TI - Hyperbaric oxygen, allopurinol, and diet-induced acute pancreatitis. PMID- 4026100 TI - Diagnostic assays in acute pancreatitis. PMID- 4026101 TI - Oral liquid furosemide in congestive heart failure. PMID- 4026102 TI - Thymus fragment transplantation in the acquired immunodeficiency syndrome. PMID- 4026103 TI - Pentamidine-associated hypotension and route of administration. PMID- 4026104 TI - Reactivation of chronic hepatitis B as acute viral hepatitis. PMID- 4026105 TI - Metoclopramide and depression. PMID- 4026106 TI - Toluene sniffing and severe sinus bradycardia. PMID- 4026108 TI - [Granulopoiesis in the alcoholic and cirrhotic patient. Exploration of neutropenia in cirrhosis using bone marrow cultures and a hydrocortisone test]. AB - Twenty per cent of 60 patients with cirrhosis (55 alcoholic patients) had neutropenia (defined as neutrophil polymorphonuclear (NP) count under 2,000/mm3). The authors tried to define the mechanism of this neutropenia and compared it with the acute bone marrow cytotoxicity of alcohol. They found that bone marrow neutrophil colony growth was normal in 7 cases of cirrhosis compared to 7 controls (with and without cirrhotic serum incubation). On the other hand, the granulocyte response to hydrocortisone test was less marked than in controls. This result suggests involvement of the late maturation process of NP and delayed release from bone marrow. PMID- 4026107 TI - [Effect of ethanol on human polynuclear neutrophils. In vitro and in vivo study]. AB - Human polynuclear neutrophilic function was studied to determine the role of alcohol in the increased susceptibility to infection of chronic alcoholics: in vitro studies investigated the effects of different concentrations of ethanol; in vivo studies included comparison with healthy subjects after alcohol intake, with excessive drinkers without liver disease and with chronic alcoholics with confirmed cirrhosis. In vitro depression of polynuclear neutrophilic function was observed only with significantly higher concentrations of ethanol than encountered clinically. In social and excessive drinkers, phagocytosis was decreased but there was no change in bactericidal activity. On the other hand, in cirrhotic alcoholics chemotaxis, phagocytosis and bactericidal activity were all significantly reduced. A direct action of alcohol alone on polynuclear function would not seem to be the cause of the increased risk of bacterial infection of chronic alcoholics. PMID- 4026109 TI - [Alcohol and urticaria]. AB - The relationship of alcohol intake and urticaria is complex. The mechanism of action may be related to a hypersensitivity reaction to ethyl alcohol or to the other components of alcoholic drinks. Urticaria may also result from the pharmacological effects of alcohol or from the histamine content of the drink. The authors review the literature about hypersensitivity to alcohol and to the different components of alcoholic drinks, especially added compounds. The appropriate sensitivity tests for making this diagnosis are described. PMID- 4026110 TI - [Alcohol, immunity and cancer]. AB - The immunological equilibrium is greatly affected by the ingestion of alcohol and this could possibly be a cancerogenic mechanism. This hypothesis not been yet tested experimentally. This paper reviews the circumstantial evidence which does not allow any definitive conclusions. PMID- 4026111 TI - [Cardiac insufficiency: new hope in its therapy]. PMID- 4026112 TI - [Role of dihydralazine in the treatment of chronic cardiac insufficiency]. AB - Dihydralazine, sold under the name of Nepressol, is the derivative of the hydrazinophthalazines used in France for the treatment of severe cardiac failure. The hydrazinophthalazines act in cardiac failure by decreasing systemic arterial resistance and increasing cardiac output without causing tachycardia or increasing myocardial contractility in normal or hypotensive subjects. The hydrazinophthalazines are metabolised by N-acetyl-transferase in the liver. The hepatic concentration of this enzyme is genetically determined. The immediate haemodynamic results observed with 100 to 300 mg/daily of Nepressol are impressive: an 86 p. 100 increase in cardiac output; a 75 p. 100 decrease in systemic valvular resistance; a 25 p. 100 fall in left ventricular filling pressures. These haemodynamic results are maintained at long-term (3 to 48 months). This treatment is associated with an improvement in symptoms and functional capacity. However, its efficacy in improving survival has not been demonstrated. Immunological complications giving rise to a lupic syndrome result only in biological changes and do not influence management. PMID- 4026113 TI - The assessment of a modification to the acetone/triacetin clearing technique as used in the measurement of airborne asbestos dust. PMID- 4026114 TI - Absorption of gases in the respiratory tract. PMID- 4026115 TI - Sampling and analysis of bitumen fumes. PMID- 4026116 TI - An instrument for measuring the concentration of combustible airborne material. PMID- 4026117 TI - Bell's palsy in children. Cases of progressive facial nerve degeneration. AB - Bell's palsy in children occurs infrequently and carries a good prognosis for ultimate recovery. However, results of electrical testing have been reported only sparsely. This paper details the authors' experience with five patients under age 18 who met the criteria for facial nerve decompression in adults. All underwent decompression via the middle fossa and manifested a lesion of the nerve, ie, edema and hyperemia in the geniculate ganglion, meatal foramen, and internal auditory canal. A discussion of pathogenesis and a literature review is included. PMID- 4026118 TI - Nasogastric intubation as sole treatment of caustic esophageal lesions. AB - In this partly retrospective and partly prospective study, we examined 200 patients with suspected caustic ingestion. No steroids were administered to the patients involved. Lesions in the esophagus were found in 93 patients. Thirty-two patients with deep circular burns had nasogastric tubes inserted immediately. Of these patients, two developed esophageal strictures, but subsequent dilatation was successful. No stricture formation was observed in the group of patients with noncircular lesions. We feel that this low percentage of stricture formation is due to the use of nasogastric tubes. Since neither the presence nor the severity of esophageal burns is predictable, an endoscopy should be performed in all suspected cases. In the absence of severe pharyngeal lesions, the use of a flexible fiberoptic endoscope is preferable because it also allows examination of the stomach and proximal part of the duodenum. PMID- 4026119 TI - Thyroid carcinoma in children and adolescents. AB - Carcinoma of the thyroid gland, although fairly common in young adults, is uncommon in the first two decades of life. Because therapy is controversial, it is important to study a relatively large group of patients treated in a single department. This report records the findings and responses to treatment in 40 cases of thyroid gland carcinoma in children and adolescents treated from 1953 to 1982. PMID- 4026120 TI - Multiview videoendoscopic evaluation of velopharyngeal physiology in 15 normal speakers. AB - Oral and nasal videoendoscopic procedures, when used in tandem, could provide a more useful analysis of velopharyngeal physiology than either procedure used alone. The purposes of this research were to document observed differences between the two approaches when applied to the examination of velopharyngeal function and to determine the advantages and disadvantages of using oral and nasal endoscopy as tandem diagnostic tools. The results indicated that patterns of velopharyngeal closure as observed from both the oral and nasal views are in approximately 60% agreement. Differences between the two perspectives most frequently involve the relative contributions of the pharyngeal walls. These differences are attributed to important physiologic variations along the vertical plane of the velopharynx. The data indicate that using oral and nasal videoendoscopy as tandem diagnostic procedures can result in improved understanding of velopharyngeal physiology. The issues of interference with speech movements and patient compliance are discussed. PMID- 4026121 TI - Ossicular and otic capsular lesions in LP/J mice. AB - Otosclerosis is an inherited disease in which abnormal bone growth results in ossicular fixation and hearing loss. Although the disease affects up to 10% of humans, it has not been observed in other animals. The LP/J inbred mouse has been found to develop abnormal bony lesions of the middle ear which resemble human otosclerosis. In this study of 113 temporal bones from LP/J mice, we found that the lesions develop after puberty and involve only the ossicles and the otic capsule. The most frequent site of involvement was the incus (46.9%), followed by the anterior crus of the stapes (31.3%), the malleus (14.2%), the otic capsule (14.2%), and the stapes footplate (8%). Cochlear hair cell loss was progressive throughout the lifespan of these animals. Although this disease is not identical in histologic appearance to human otosclerosis, understanding its disease process may shed light upon the pathophysiology of the human disease. PMID- 4026122 TI - Aspiration in head and neck surgical patients. AB - Aspiration, the entry of material into the airway below the true vocal folds, has been reported in various types of postsurgical head and neck patients. This study was designed to examine radiographically a group of 30 head and neck surgical patients with postoperative swallowing difficulties and to identify the relationship between the physiologic causes of aspiration in each patient and the surgical procedure. The modified barium swallow technique is needed to identify the nature of aspiration in these patients. Aspiration before, during, and after the swallow was caused by a variety of problems including reduced tongue control, delayed triggering of the swallowing reflex, reduced glottic closure, reduced laryngeal elevation, and reduced pharyngeal peristalsis. Eight patients exhibited two causes of aspiration. No one food consistency caused greater aspiration in all patients. The best and worst food consistencies varied with the cause of aspiration. PMID- 4026123 TI - Efficacy of a monothermal warm water caloric screening test. AB - The validity of using monothermal caloric screening tests to shorten bithermal caloric test time has been disputed by several investigators. The purpose of this study was to reexamine the efficacy of a monothermal warm caloric screening test. Two retrospective investigations (n = 130) served to generate normative data and provide an estimate of the false-negative rate of the warm monothermal caloric screening test. A prospective investigation (n = 30) was also conducted. Predictions were made regarding bithermal caloric test normality from warm monothermal data, and the bithermal test was completed. The results of this prospective investigation suggested that a warm monothermal screening test can predict normal bithermal caloric responses with greater than 97% accuracy. Criteria for normality include less than 29.54% warm caloric maximum slow phase eye velocity (SPEV) interaural difference, maximum SPEVs that are greater than 11 degrees/s for each ear, absence of significant positional or spontaneous nystagmus, and normal ocular motility. PMID- 4026124 TI - Rigid transbronchial needle aspiration biopsy for histological specimens. AB - Transbronchial needle aspiration of cytopathological specimens has proven useful in the diagnosis and staging of bronchogenic carcinoma, but its value in conditions requiring histologic confirmation has been hampered by the small size of the sample provided. To expand the utility of this procedure, we designed a larger (18 gauge) needle with a beveled stylet with which tissue cores for histologic study can be obtained during rigid bronchoscopy, and we have evaluated the safety and efficacy of this technique. Diagnoses of five neoplastic and three granulomatous diseases were established in eight of the ten patients with this procedure, and there were no complications. These findings suggest that transbronchial needle aspiration biopsy is relatively safe and effective, further extending the bronchoscopic approach to selected patients with mediastinal disease. PMID- 4026125 TI - Modifications of collagens in the course of inflammatory tracheal stenoses. AB - A comparison was made between the biochemical and histological properties of collagens contained in samples of normal tracheas obtained at autopsy or of stenosed tracheas obtained during surgery. The amounts of total collagen solubilized by pepsin was increased seven times in the pathological samples, and the proportion of cartilage type II collagen decreased by about one half, being replaced by type I collagen, whose ratio was increased five times. Microscopic studies confirmed that cartilage underwent a degenerative process and was progressively infiltrated by fibrils of interstitial collagen. PMID- 4026126 TI - Enzymes of acetylcholine metabolism in the rat cochlea. AB - The distributions within the rat cochlea of choline acetyltransferase and acetylcholinesterase activities were measured to evaluate the prominence of cholinergic mechanisms in cochlear function. Samples obtained by microdissection of freeze-dried bony labyrinths were assayed radiometrically. Activities of both enzymes were highest in regions containing olivocochlear fibers and terminals, especially the organ of Corti and spiral ganglion. Within the organ of Corti, activities of both enzymes were consistently higher in the vicinity of the inner hair cells than in that of the outer hair cells and were much lower in the apical turn than in middle or basal turns. Surgical cuts in the brain stem transecting the olivocochlear pathway on one side led within seven days to total loss of choline acetyltransferase activity in the ipsilateral organ of Corti. It is concluded that all cholinergic structures in the rat organ of Corti derive from the brain stem and that synapses on or near both inner and outer hair cells are cholinergic. PMID- 4026127 TI - Ciliary activity of the middle ear lining in guinea pigs. AB - Since the middle ear lining is an extension and a modification of the respiratory epithelium, it is conceivable that it has a mucociliary system and plays an important role in clearing the middle ear cavity. It has already been noted in morphological investigations that the middle ear mucosa has ciliated cells. To our knowledge, however, ciliary activity has never been observed directly. In our research, we used the photoelectric method to study ciliary activity of the middle ear mucosa directly and quantitatively. We made special reference to the frequency of ciliary beating at various sites within the middle ear cavity. Ciliary activity was found to exist in the eustachian tube and the middle ear, the same as in other respiratory organs, and this activity was stronger in cells distal to the eustachian tube. PMID- 4026128 TI - Electronystagmographic findings in posterior fossa metastases. PMID- 4026129 TI - Nerves and neurotropic carcinomas. AB - Neurotropism by a carcinoma in the head and neck refers to invasion in, around, and through peripheral nerves. This invasion may be along planes of least resistance in the connective tissue coverings of the nerve or less frequently by endolymphatic spread. The only lymphatics associated with a nerve are those in the perineural covering and in the epineurium. Such malignant neurotropism is to be distinguished from benign epithelial inclusions simulating neural invasion. PMID- 4026130 TI - [Mycobacterium chelonei cutaneous infections. General review apropos of a case]. AB - Mycobacterium chelonei is a facultative pathogen which exists as a saprophyte in the environment and rarely produces clinical manifestations in humans. We describe a 62-year-old woman, long-term treated with low-dose steroids for severe asthma, who presented sporotrichoid-like lesions on one leg. These lesions appeared two months after a cat-scratch and were present for six months. Histological examination showed acute inflammation with polymorphonuclear infiltration without tuberculoid granuloma nor caseation necrosis. Ziehl-Neelsen stains were negative. Mycobacteria were found by direct examination and Mycobacterium chelonei chelonei was identified by culture. Treatment with isoniazid, rifampicin and ethambutol was given for one month and followed by complete resolution of the lesions, though each of these antibiotics was not effective in vitro. The literature about Mycobacterium chelonei infections is reviewed and the role of the antibiotherapy in clinical recovery is discussed. PMID- 4026131 TI - [Unusual and unknown aspect of cutaneous malignant melanoma: minimal deviation malignant melanoma. Retrospective study of 45 cases]. AB - Minimal deviation malignant melanoma (MDMM) is a rare melanocytic tumor of the skin that shares both malignant and benign histologic features: 1) a vertical growth phase similar to that of malignant melanomas with expansile nodules invading throughout the reticular dermis (Clark's level IV), and even the subcutaneous fat (Clark's level V); 2) but a monotonous and uniform proliferation of melanocytic cells that are only moderately atypical. A very slight cellular maturation from the top to bottom of the lesions may be observed, but usually there is no maturation at all. By themselves, the cells do not appear as malignant. A borderline variant of MDMM shows identical cytological and growth pattern features, but remains confined to a Clark's level III of invasion. Over the past 14 years, 45 cases (female to male ratio: 1.5:1.0) of MDMM, 8 of which were of the borderline variant, were observed. The lesions appeared as acquired pigmented tumors, 0.5 to 1.0 cm in size which predominated on the trunk. Young adults (mean age: 34 years) were most frequently involved. Based on the cytological characteristics of the cellular proliferation, they could be subdivided in 4 groups: 1) epithelioid and spindle cell type (15 cases); 2) epithelioid type (14 cases); 3) spindle cell type (7 cases); and 4) pigmented spindle cell type (9 cases). The mean thickness of the 45 cases was 3.06 mm (1.24 mm for the borderline lesions; 3.40 mm for the MDMM). Tumors with a spindle cell component appeared thicker than those without. Mitoses were numerous (mean: 3.2/10 high power fields). Each tumor but one showed a junctional component. This appeared as melanocytic hyperplasia or melanocytic nests at the dermoepidermal interface. Moreover, 10 cases (7 MDMM and 3 borderline tumors) disclosed intraepidermal spread of melanocytes. However, as observed with the dermal component of the lesions, these intraepidermal melanocytes never appeared cytologically malignant, although moderate atypism could be observed. At last, an association with a compound or dermal nevus was seen in 8 cases. MDMM appears as a particular subgroup of cutaneous malignant melanomas with distinct and characteristic histologic features. Its differential diagnosis includes blue nevus, especially the cellular variant, combined nevus, spindle and epithelioid cell nevus (Spitz-Allen's nevus) and cutaneous metastasis of malignant melanoma. The most important features for the differential diagnosis are the growth pattern, the absence of cellular maturation, the absence of real malignant cells and moderate cellular atypism.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 4026132 TI - [Role of an anti-estrogen, tamoxifen, in the treatment of metastatic malignant melanoma]. AB - The hormone-dependence of malignant melanoma is brought to mind by some epidemiological facts (rarely found in children, more frequently in females, higher frequency in case of prolonged use of oral contraceptives from an early age). On the other hand, estrogen receptors can be found in about 30 p. 100 of malignant melanomas. Starting from this hypothesis of a sub-population of hormone dependent malignant melanomas, it seemed of interest to us to study the efficiency of an anti-estrogen, namely Tamoxifen (Nolvadex) in the management of metastatic malignant melanoma. It was used at a 40 mg daily dose-regimen on four patients (three post-menopausal females, one male) with multiple estrogen positive cutaneous metastases. In post-menopausal women, two cases of total regression were observed, associated with a distinct increase in progesterone receptors while under treatment and with a return to the initial stage when the treatment was stopped. This phenomenon can be explained by a double self contradictory effect of the drug, already well known in other hormone-dependent cancers such as those of the breast or the endometrium, namely an anti-estrogen result on the tumoral growth and an estrogen result as attested by the synthesis of progesterone receptors. Certain malignant melanomas therefore behave as endocrine-dependent tumours and may so answer an anti-hormone treatment through a competitive fixation on estrogen-receptors. Our clinical results are in agreement with such a theory since Tamoxifen is at best effective on cutaneous metastases of post-menopausal women. The overall efficiency on all metastases is of the order of 10.6 p 100 (complete or partial regression).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4026133 TI - [Leprosy in young children. 2 cases at 3 years of age]. AB - Two children (age 3 years) presented with leprosy in endemic area: one was type T (tuberculoid paucibacillary); the other was type BL (borderline lepromatous) considering a very fast evolution, and was treated as a multibacillary leprosy. The family of the second child reported that the onset of the disease was consecutive to an insect bite at 5 1/2 months of age. Such observations remind us that leprosy must be suspected or thought about very early since the incubation period is likely to be shorter than previously proclaimed. PMID- 4026134 TI - [Trigeminal neurotrophic ulceration after thermocoagulation of Gasser's ganglion: apropos of a case with involvement of 3 areas of the trigeminal nerve]. PMID- 4026135 TI - [Brachytelephalangy disclosed by nail dystrophies induced by cryotherapy]. PMID- 4026136 TI - [Current concept of abdominal traumatology in children]. PMID- 4026137 TI - [Acute intracranial hematoma in neonates at term. Apropos of 17 cases]. PMID- 4026138 TI - [Standard frontal radiography in isolated pulmonary valve stenoses]. PMID- 4026139 TI - [2 new cases of ring chromosome 14]. PMID- 4026140 TI - [Deletion of the short arm of chromosome 18, holoprosencephaly and pitressin sensitive diabetes insipidus]. PMID- 4026141 TI - [Chronic meningococcemia in a 16 1/2-month-old child]. PMID- 4026142 TI - [Panhypopituitarism (disclosed by hyponatremia) immediately following a head injury]. PMID- 4026143 TI - [Tricho-rhino-phalangeal syndrome. Apropos of a neonatal case]. PMID- 4026144 TI - [Profile of convulsions in infants and young children in Brazzaville (Congo)]. PMID- 4026145 TI - [The Meningococcus and its pathology. A symposium sponsored by the French Language Society for Infectious Pathology]. PMID- 4026147 TI - [Idiopathic calcinosis]. PMID- 4026146 TI - [Visceral and parietal malformations associated with cervical and dorsal spine abnormalities. The viewpoint of the pediatric orthopedic surgeon]. PMID- 4026148 TI - [Convulsions with 3 antitussive substituted derivatives of piperazine (zipeprol, eprazinone, eprozinol)]. PMID- 4026149 TI - [Apical pulmonary sequestrations in children. Apropos of 3 cases]. PMID- 4026150 TI - [Trisomy syndrome of the end section of the long arm of chromosome 4]. PMID- 4026151 TI - [Chronic erythroblastopenia with hyposplenism in a 10-year-old girl]. PMID- 4026152 TI - [Favorable outcome of a recurring malignant adrenocortical tumor under O,P'-DDD therapy]. PMID- 4026153 TI - [Membranoproliferative glomerulonephritis with dense deposits associated with hepatitis B viral infection]. PMID- 4026154 TI - [Analysis of 1,165 autopsies of children in 3 hospital departments in Iran]. PMID- 4026155 TI - [Can the treatment of pulmonary superinfections in children with cystic fibrosis be maximized?]. PMID- 4026156 TI - [Advice and prescriptions for infants preceding the departure of an Algerian family for Algeria]. PMID- 4026157 TI - [Ulcer recurrence after fundus vagotomy for duodenal ulcer. Incidence. Epidemiology]. PMID- 4026158 TI - [Hydatid cysts of the liver rupturing into the bile ducts. Therapeutic procedures]. PMID- 4026159 TI - [Post-traumatic spinal epidural hematoma. 8 cases]. PMID- 4026160 TI - [Post-traumatic false aneurysm of the celiac trunk. Apropos of a case]. PMID- 4026161 TI - [Proximal wound of the upper mesenteric artery. Apropos of a case treated with success]. PMID- 4026162 TI - [Monoclonal antibodies in the diagnosis and treatment of hepatic metastases of colo-rectal cancers]. PMID- 4026163 TI - [Hemodynamic effects of intravenous acebutolol in the acute phase of myocardial infarction]. AB - The haemodynamic tolerance of intravenous acebutolol was evaluated during the acute phase of myocardial infarction. This is a beta-blocker with an intrinsic beta-stimulant effect. The study consisted of 14 patients (10 cases of inferior infarction and 4 cases of anterior infarction) with a mean capillary pressure of less than 20 mmHg and a cardiac index greater than 2 l X min-1 X m-2. The minimal dose of acebutolol was 0.05 mg X kg-1 X h-1 and the maximal dose was 0.125 mg X kg-1 X h-1. The intravenous infusion of acebutolol was commenced between 3 and 12 hours (average: 7.5 hours) after the infarction and was continued for 48 hours, at which time it was replaced by oral administration. The mean total intravenous dose was 409 mg (from 190 to 510 mg). Two patients were excluded from the protocol because of the development of 2nd degree atrioventricular block several minutes after the beginning of the infusion. The basal values of the cardiac index (2.7 l X min-1 X m-2 +/- 0.37), the mean capillary pressure (9.4 mmHg +/- 2.7) and the systolic index (38.3 ml/m2 +/- 6.4) did not change significantly during the infusion, in the 14 patients studied. The double product, heart rate x blood pressure, decreased from the mean basal value of 9,443 to 7,680 at 24 hours and to 7,000 at 48 hours (p less than 0.05). Acebutolol does not depress left ventricular function, provided that it is reserved for patients with class I or II disease according to Killip and Kimball's classification.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4026164 TI - [Torsades de pointe. Apropos of 60 cases]. AB - The authors report a personal series of 60 cases of "torsade de pointe" (the largest series published to date) seen in the Cardiology department of Amiens Hospital over a period of 11 years. They review the essential features of this arrhythmia, which was well described by F. Dessertenne in 1966, but which is still sometimes confused with certain forms of ventricular tachycardia. "Torsade de pointe" is still a topical issue, as 25% of the cases in this series were seen over the last two years. These cases were classified into three groups according to their aetiology: severe bradycardia (21 cases), potassium depletion (16 cases), drug causes (23 cases). This arrhythmia was essentially associated with iatrogenic factors, in particular potassium depletion (41.6% of cases). The classical notion of predisposed patients was confirmed: elderly patients (mean age of 68 years), with cardiovascular disease in 70% of cases (i.e. heart failure or coronary insufficiency, hypertension) and with a marked female predominance (70% women). The ECG between episodes of "torsade de pointe" always revealed a prolonged QT interval which, in relation to the heart rate, was more marked in the patients with potassium depletion. During an attack, the average ventricular rate was 210/min (range: 170 to 290/min). 20% of cases subsequently developed ventricular fibrillation. The overall mortality was 16.6% (10 out of 60 cases), but there have been no deaths since 1977 due to the better understanding of this arrhythmia.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4026165 TI - [Outcome of patients with inoperable multivessel coronary disease]. AB - The authors studied the clinical course of 100 patients with two or three vessel coronary artery disease who were unsuitable for surgery because of the poor quality of the distal vascular bed or excessively depressed left ventricular function. The 6 year actuarial survival was 58 per cent; 43 of the 100 patients did not present any serious cardiac events causing death or requiring further admission to hospital, over this follow-up period. The severity of the clinical course in women and the presence of heart failure prior to coronary angiography were considered to be among the most important clinical prognostic factors. On the basis of the haemodynamic survey, the probability of survival or the risk of a further coronary accident appears to depend more on the extent of the left ventricular kinetic abnormalities than on the ejection fraction or the severity of the coronary lesions. PMID- 4026166 TI - [Total obstruction of the anterior interventricular artery without myocardial infarction]. AB - Complete proximal occlusion of the the anterior interventricular artery was associated with the presence (group A: 31 cases) or the absence (group B: 31 cases) of transmural myocardial necrosis in the corresponding territory. The aim of this study was to define the factors which determine the development of permanent myocardial necrosis, on the basis of clinical, electrocardiographic, haemodynamic and angiographic criteria. Group B was characterised by the following features: almost all of the patients (30 out of 31) had unstable angina, for less than 2 months in half of the cases; 67% of cases presented an abnormality of ventricular repolarisation on the resting ECG, usually (54 per cent of cases) in leads V3 to V5, suggestive of isolated sub-pericardial ischaemia in half of these cases; 24 cases presented moderate regional hypokinesia in the anteroapical territory of the LV; the distal AIV artery was more clearly visualised (17 cases had a well perfused AIV artery compared with 6 in group A) and a greater number of patients obtained homocoronary interseptal re perfusion (8 versus 2) and heterocoronary re-perfusion by distal anastomosis of the AIV artery and the PIV artery by the apex (13 versus 3) (p less than 0.05) than in group A. However, the possibility of surgery was considered to be limited (39%) on the basis of the angiographic criteria. Thus, in group B, a "phantom AIV artery syndrome" can not be distinguished from unstable angina on the basis of the clinical and electrocardiographic profile.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4026167 TI - [Transmural myocardial infarction. An impossible electrocardiographic diagnosis]. AB - The anatomical and experimental data clearly show that transmural myocardial infarction does not always produce a pathological Q wave on the ECG, but may sometimes only cause abnormalities of the ST segment and the T wave. Conversely, a sub-endocardial myocardial infarction may present with pathological Q waves. Schematically, the histology of transmural myocardial infarction usually reveals so-called coagulation necrosis, while sub-endocardial myocardial infarction generally corresponds to myofibrillary degeneration (contraction band necrosis), which promotes a reperfusion process. Very often, however, the histological appearance is not so clear-cut and the features tend to overlap. Consequently, in practice, it does not seem justified to use the electrocardiogram as a basis to distinguish between transmural and sub-endocardial infarctions, in terms of prognosis, or to select possible candidates for coronary angiography following a first myocardial infarction. PMID- 4026168 TI - [Dispersion of auricular refractory periods. Role of the intensity of the stimulation current]. AB - In a series of 12 patients, the right atrial effective and functional refractory periods (ERP and FRP) were determined at 3 different sites and at 3 different intensities (threshold intensity and double and triple the threshold intensity). The mean of the range of the ERP in the same atrium was 43.4 ms and that of the FRP was 53.5 ms. These ranges appear to be independent of the intensity of stimulation. However, the values of the refractory periods were strictly correlated with the intensity of the stimulation current used. This correlation appeared to be much more marked for the ERP than for the FRP. PMID- 4026169 TI - [Endocavitary electrocautery of a right anterior bundle of Kent]. AB - The authors report another case of successful endocavitary electrocautery in a young woman with Wolff-Parkinson-White syndrome. The pre-excitation was controlled by the administration of two 250 joule electrical shocks applied to the atrial origin of the right anterior bundle. The clinical and laboratory tolerance were satisfactory. Although these results are encouraging, other studies are required in order to define the indications and protocols of electrocautery of accessory pathways. PMID- 4026170 TI - [Multiple systolic clicks. Unusual auscultation of Starr Edwards valves implanted in the aortic position. Apropos of a case]. AB - The authors report the case of unusual auscultatory findings, multiple systolic clicks, in a patient with a Starr-Edwards model 1 260 aortic valve replacement, six years after the implantation. The aetiology of this anomaly appears to be incorrect positioning of the prosthetic valve ring. PMID- 4026171 TI - [Echocardiographic diagnosis of a rare mechanical complication of biventricular infarction. Rupture of the free wall of the right ventricle]. AB - The authors report a case of rupture of the free wall of the right ventricle, diagnosed by two dimensional echocardiography. This examination revealed an intrapericardial clot associated with a fissure of the diaphragmatic wall of the right ventricle. This case emphasises the value of two dimensional echocardiography in the acute phase of myocardial infarction for the diagnosis of complications which require urgent surgical treatment. PMID- 4026172 TI - [Thromboembolic complications and permanent endocavitary stimulation catheters]. AB - Based on four cases of phlebitis associated with permanent intravenous cardiac stimulation catheters, the authors review the pathophysiology, clinical signs, diagnosis and treatment of this disease. The insertion of the catheter causes varying degrees of radiologically detectable thrombosis in 30 to 50 per cent of cases. The most frequent clinical presentation is the typical picture of phlebitis of the upper limb due to axillo-subclavian thrombosis. However, clinical signs are only present in 0.5 to 5 per cent of cases (1.7 per cent of cases in the present series). The risk of this complication can not be predicted on the basis of delay after the implantation. The incidence is increased in patients with more than one stimulating electrode, but this disease is not confined to this group of patients. The thrombosis may affect the superior vena cava or the right cardiac cavities, when it may also be associated with pulmonary embolism, as in one of the cases in this series. One case with arteriolar involvement (phlegmatia cerulea) is also described. The diagnosis may require impedance rheoplethysmography, two dimensional echocardiography, isotope phlebography or contrast phlebography, which remains the most frequently used technique. The treatment is medical, consisting of intravenous or subcutaneous heparin. Fibrinolysis may be indicated in cases with recent superior vena cava thrombosis and or other complications. To our knowledge, no controlled studies have been performed to define the optimal treatment. Long term prophylactic anticoagulant therapy is useless. There is never any indication for removal and replacement of the catheter responsible or for the removal of useless catheters left in place in patients with multiple implants. PMID- 4026173 TI - A rare complication of anastomotic leakage after low anterior resection of the rectum. PMID- 4026174 TI - Reoperation for gastro-esophageal cancer. PMID- 4026175 TI - Oesophageal atresia and respiratory complications. Matti Sulamaa lecture-30th May 1983. PMID- 4026176 TI - The state of health of patients previously operated on for primary hyperparathyroidism compared with randomized controls. AB - 240 patients operated on for PHPT in the years 1956-79 were compared with 240 sex and age matched randomized controls to examine the present state of health of the patients. Diseases which occurred in both groups were registered to clarify their possible association with PHPT. Recurring urinary tract infections occurred as often in both groups, though renal stones had naturally been more frequent in the PHPT group. Serum creatinine was elevated in 33 PHPT patients and in 9 controls (p less than 0.001), and renal damage was also more severe in the PHPT patients. Malaise and fatigue occurred in 29 PHPT patients and in 14 controls (p less than 0.05). Medically treated hypertension was found in 95 PHPT patients and in 53 controls (p less than 0.001). Eight PHPT patients and one control had had pancreatitis (p less than 0.01). Peptic ulcer disease and gallstones were registered as frequently in both groups. 16 PHPT patients and three controls had received previous irradiation to the neck region (p less than 0.01). Six PHPT patients, but none of the controls, had had a differentiated non-medullary thyroid carcinoma. Two of the thyroid carcinoma patients had received irradiation. Other malignant diseases were as frequent in both groups. Three controls were hypercalcaemic and had PHPT verified at operation. The prevalence of PHPT in the control group was 1.25%. The state of health was normal in 52% of the PHPT patients and in 68% of the controls (p less than 0.001). The results indicate that PHPT permanently deteriorates the health of the patients and should therefore be diagnosed and treated as early as possible in the course of the disease. PMID- 4026177 TI - Observations on 334 patients operated on for primary hyperparathyroidism. AB - 334 patients were operated on for PHPT during the years 1956-79. A follow-up study of the material was performed during the years 1980-82 and it included 289 patients. The material was divided into single adenoma (SA) and multiglandular disease (MGD) cases. The initial diagnosis of SA given by the primary operation was later changed in 12 patients (4%) by reoperations performed for persistent or recurrent hypercalcaemia; the follow-up study changed the diagnosis in four patients. The proportion of MGD in the follow-up material was 15.2%. Reoperations were performed in 4% in the SA group and in 29% in the MGD group. The primary results concerning the serum calcium level were good in both SA and MGD groups, but, at the follow-up study 1.6% of the patients in the SA group and 41% of the patients in the MGD group were hypercalcaemic (serum calcium over 2.65 mmol/l). The hypercalcaemia at the follow-up study was, however, slight in general (mean 2.75 +/- 0.09 mmol/l). In the whole material, permanent hypoparathyroidism occurred in 1.2%, permanent unilateral vocal cord paralysis in 0.9% and permanent bilateral vocal cord paralysis in 0.6%. Operative mortality was 0.9%. The "conservative" strategy used in the whole material gave good results in SA patients but considerably worse results in MGD patients. Accordingly, MGD patients should be operated more "radically". PMID- 4026178 TI - Anaemia in primary hyperparathyroidism--fantasy or reality. AB - Controversy exists as to whether primary hyperparathyroidism is associated with an anaemia. Records corresponding to 215 patients operated on at the Karolinska Hospital between 1972 and 1981 were reviewed. An incidence of 7.4% of anaemia was found, but in only 3% of these cases the anaemia could not be explained by any other known cause. The anaemic group was characteristic in presenting a normochromic and normocytic picture, with iron and serum transferrin values below the normal range. No renal or osseous pathology was observed. In these patients, the anaemia disappeared after the parathyroidectomy, and iron values remained below the normal range. In conclusion, a mild normochromic and normocytic anaemia that disappeared after parathyroid surgery was observed in six patients with PHPT (3%). Its mechanisms are obscure, but data available suggest that parathyroid disease could be of aetiological importance. PMID- 4026179 TI - Prognostic indicators in burned patients. AB - The clinical course and outcome of 64 burned patients treated in the intensive care unit were analysed in order to find indicators for prognosis. Total burn area varied from 7 to 90% of body surface area. 17 patients (27%) died. In addition to the extent of burn injury and nature of it, e.g. airway burns, disturbances in some biochemical parameters were associated with increased mortality. These were disturbances in haematocrit, thrombocyte numbers, arterial pH, serum protein concentration and serum osmolality during the first three days of treatment. By means of a logistic model factors were obtained which proved most significant for prognosis; these were the age of the patient, arterial pH and serum protein concentration at the beginning of the treatment. The results suggest that the extent of the burned area is not the only factor affecting the outcome of the patient. PMID- 4026180 TI - Wertheim radical hysterectomy. Surgical complications, accuracy of clinical staging and value of lymphangiography in cervical carcinoma. AB - Wertheim radical hysterectomy combined with pelvic lymphadenectomy was performed at the Helsinki University Central Hospital on 132 women of whom 120 had cervical carcinoma from Stage IA to early IIB and 12 had endometrial carcinoma Stage II. None of the patients died or had severe complications during their hospitalisation. The left ureter was accidently transected in two patients and both were corrected immediately. Wound complications occurred in 16 patients (12%). The high incidence of wound complications is probably partly related to the low-dose heparin prophylaxis. The initial clinical staging was found to be correct in 85% of the cases. Five cases were under-staged. All ten patients cases of early Stage IIB were over-staged, none of whom had parametrial invasion. The predictive value of lymphangiography was low, 14% in histologically positive cases and 89% in negative cases of lymph node metastases. Lymphangiography proved to be only of value in facilitating complete lymph node dissection. Intra operative lymphangiographic control revealed radio-positive nodes and lead to further dissection in 30 patients (24%). PMID- 4026181 TI - Eosinophilic gastroenteritis with no peripheral eosinophilia. AB - A 41-year-old female with intermittent abdominal pain and diarrhea for a period of three years was found to have eosinophilic enteritis. The patient has had neither a history of atopy nor peripheral eosinophilia, commonly reported in association with eosinophilic enteritis. The patient made a rapid clinical response to steroid therapy. The literature on eosinophilic gastroenteritis is reviewed. PMID- 4026182 TI - The biochemist's contribution to the clinical process. PMID- 4026183 TI - Systemic availability of oral slow-release morphine in man. AB - In a within-patient crossover study on twelve patients we investigated plasma morphine concentrations for 48 hours after administration of intravenous morphine sulphate followed 24 hours later by oral MST Continus [MST]. Patients received either 10 mg i.v. morphine followed by 10 mg MST or 20 mg i.v. morphine followed by 2 X 10 mg MST tablets. Systemic clearance of morphine was low, being about 3 ml/min/kg after both intravenous and oral administration. The ratio of the areas under the concentration-time curve for MST relative to that for i.v. morphine was about 1:1 for 20 mg doses, but was significantly greater than 1:1 for 10 mg doses. The results suggest high oral systemic availability for morphine and low hepatic morphine metabolism. PMID- 4026184 TI - Plasma bile salt levels in patients presenting with generalised pruritus: an improved indicator of occult liver disease. AB - Fasting plasma bile salt concentrations were measured in 26 patients presenting to a Skin Department who had generalised pruritus without primary skin disease, as part of a screening investigation for systemic causes of pruritus. The results were compared with conventional tests of hepatic function. Plasma-conjugated cholate measurements identified all patients with hepatobiliary disease. Conventional liver function tests were abnormal in these patients but also in five patients with no other evidence of hepatic dysfunction. Fasting conjugated cholate measurements offer a useful screening test for identifying hepatobiliary disease in patients presenting with generalised pruritus. PMID- 4026186 TI - Immunoturbidimetry of serum C-reactive protein in low concentration of polyethylene glycol. AB - A simple, rapid immunoturbidimetric assay for determination of serum C-reactive protein is presented. In order to obtain constant sample blank values within a few minutes we found it necessary to use a low concentration (10 g/L) of polyethylene glycol 6000 in contrast to the commonly used 40 g/L PEG solution. The sensitivity of the assay presented is 7 mg/L; within-run and between-run CVs ranged respectively from 1.4% to 2.4% and from 2.1% to 5.5%. Results obtained with the proposed method correlate well with radial immunodiffusion. PMID- 4026185 TI - Comparison of three different assay procedures for the determination of HbA1 with special attention to the influence of pre-HbA1c, temperature and haemoglobin concentration. AB - Three different methods for the measurement of glycated haemoglobin or HbA1, based on agar gel electrophoresis, ion-exchange and affinity chromatography were compared. All three showed acceptable precision (overall CV being less than 5%) and correlated well with each other (r greater than 0.945). The ion-exchange and affinity chromatography method proved to be independent of the amount of pre HbA1c present. The electrophoresis method was independent of temperature in contrast to the other two methods, which showed a strong and comparable temperature dependency. All three methods were dependent on the haemoglobin concentration and/or protein content of the haemolysate. Both ion-exchange and electrophoresis showed significant interference by changes in haemoglobin concentrations, whereas the protein concentration significantly biased the affinity chromatography figures. Taking into account their specific merits all three methods are acceptable for routine use. PMID- 4026187 TI - External quality assessment of urinary pregnancy oestrogen assay: further experience in the United Kingdom. AB - Four years' experience with external quality assessment of urinary pregnancy oestrogen and creatinine assays using a revised scheme design, incorporating frequent distributions, individualised reports and running scores based on variance index scores, is described. During this period there was a rapid and substantial improvement in interlaboratory agreement, which appears attributable in part to these improvements in scheme design. The derivation and use of a new index, the SDBIS (standard deviation of the bias index score), which assesses variability of bias, are described. Investigations showed that urine-based calibration materials could improve between-laboratory agreement; there were only minor differences in performance between method groups. PMID- 4026188 TI - Validity of the consensus mean as the target value for a small External Quality Assessment Scheme. AB - Data from 2 years' operation of an External Quality Assessment Scheme covering 14 analytes and with some 60 participants is presented. Following the trimming of discrepant results and statistical 'outliers' (outside the range of +/- 3 SD from the mean), there was generally close agreement between consensus mean values for a specimen analysed on different occasions, by different groups of laboratories, or when using different analytical methods. An improvement in performance, indicated by a reduction in the average inter-laboratory coefficient of variation was found for 11 of the 14 analytes over the 2-year period. PMID- 4026189 TI - A simple, optimised and rapid assay for urinary free catecholamines by HPLC with electrochemical detection. AB - A rapid method is described for the determination of urinary free catecholamines by HPLC with electrochemical detection. Optimised and equilibrium assay conditions are assessed for sample preparation, separation and detection. Catecholamine stability is maintained during the assay procedure by the addition of a combined reducing agent. Variability in recovery between aqueous standards and urine samples is minimised by dilution of samples with a concentrated Tris buffer solution. Ethyl acetate washing of an acid eluate is performed after and not before an alumina adsorption step in order to make the procedure as simple and rapid as possible. The method is evaluated and has thus far identified two cases of phaeochromocytoma and one case of neuroblastoma. PMID- 4026190 TI - Albumin analysis in serum of haemodialysis patients: discrepancies between bromocresol purple, bromocresol green and electroimmunoassay. AB - The analysis of serum albumin by bromocresol purple (BCP), by bromocresol green (BCG), and by electroimmunoassay (EIA) has been compared in a mixed group of 100 hospital patients. Good agreement between the immunochemical and BCP methods, but a positive bias with the BCG method led to routine use of the BCP method. In a group of 19 paediatric patients on chronic haemodialysis the mean BCP-albumin was found to be lower than the true albumin, as determined by EIA, whereas the positive bias using the BCG method remained. The difference between BCP-albumin and EIA-albumin in the haemodialysis group varied from 0 to -13 g/L (mean -7.1 g/L) but was effectively constant for most patients over a 3-month period. Possible mechanisms and necessary further investigations are discussed. PMID- 4026191 TI - The stability of creatine kinase isoenzymes studied with two-site monoclonal antibody assays. AB - The stability of human creatine kinase isoenzymes was investigated under different storage conditions using specific two-site monoclonal antibody assays. In Tris-HCl buffer pH 7.5 or barbitone buffer pH 8.1 containing 5 g/L bovine serum albumin, the isoenzymes appeared to be stable for up to 3 weeks at 4 degrees C but suffered a partial subunit dissociation and random reassociation after freeze-thawing; this dissociation was more pronounced as a result of freezing at -20 degrees C rather than at -70 degrees C. In contrast, creatine kinase isoenzymes stored in serum were stable at both 4 degrees C and following freeze-thawing. High levels of heart type creatine kinase in serum showed only minor subunit hybridisation even after 12 h at room temperature. We conclude that in practical clinical situations, subunit hybridisation in serum samples is negligible. We recommend however, that isoenzyme standards for use in either two site assays or radioimmunoassays should be stored frozen in normal serum from which endogenous creatine kinase isoenzymes have been previously removed. PMID- 4026192 TI - Studies on the nature of prolactin-like immunoreactivity in bromelin-treated cervical mucus. AB - Prolactin has been reported to be present in cervical mucus at concentrations higher than those found in blood. Our initial findings appeared to confirm this and the material fulfilled criteria of validity generally applied when an immunoassay is employed on a new biological matrix, i.e. parallelism and chromatographic identity. Further experiments demonstrated that prolactin concentrations in cervical mucus were less than 40 mU/L and the prolactin-like immunoreactivity originally detected was due to the action of the enzyme bromelin which was used to liquefy the mucus. Bromelin has a similar molecular weight to prolactin and appeared to digest prolactin tracer and reduce its ability to bind antiserum in a manner paralleling the effect of adding pituitary prolactin. PMID- 4026193 TI - The fluorimetric determination of the lecithin/sphingomyelin ratio of amniotic fluid after HPLC. AB - We have investigated whether fluorimetric determination of the lecithin/sphingomyelin ratio is feasible after HPLC. We found that the saturated phospholipid, dipalmitoyl lecithin, which is secreted by the fetal lung, and which cannot be detected by ultraviolet spectrophotometry, can be determined fluorimetrically. For this purpose we have added the fluorescence-enhancing substance, 1,6-diphenyl-1,3,5-hexatriene to the effluent. With the aid of a continuous-flow system we showed that the method can be used for a rapid assay of the ratio of these phospholipids in amniotic fluid. PMID- 4026194 TI - Increased possibilities for detecting drugs by the Toxi-Lab screening test. AB - The authors have investigated the possibility of detection of over 40 drugs and their metabolites, which are not included in the original list of the Toxi-Lab reagent set. The data on Rf-values of these drugs and the colours in detecting steps are given. PMID- 4026195 TI - [Surgical treatment of hepatic metastases]. AB - 355 patients with hepatic metastases were followed between 1970 and 1984 at the Hopital Paul Brousse. 132 cases were of colonic origin: 32 were treated by means of hepatic resection (including 5 metastasectomies), 7 by intra-hepatic anastomosis and 5 by devascularisation. The other 88 patients did not receive any surgical treatment. In 148 of the other 233 patients, the metastases were of non colonic gastro-intestinal or rectal origin and in the remaining 75 cases the metastases were derived from another site. 12 patients were treated by hepatic resection, 6 by devascularisation, 2 by intra-hepatic anastomosis and 2 by intubation of the bile ducts. One patient (0.5 per cent) died during the post operative period following these operations. The long term survival was 73 per cent at 1 year and 29 per cent at 3 years. In conclusion, some patients are definitely cured by hepatic resection, although these patients cannot be predicted. For this reason, the surgeon's role consists of trying to decrease as much as possible the operative risk and to propose this type of treatment to all patients in which it may be beneficial. PMID- 4026196 TI - [Pseudotumoral form of hepatic tuberculosis. Apropos of a case report]. AB - Concerning one case of autonomous hepatic tuberculosis in a pseudo-tumoral aspect, the difficulties of making the diagnosis are brought to light. Liver biopsy is the best examination to clarify things, either performed under ultrasonic control or during surgery. This biopsy permits pathologic examination and culture of a liver fragment in Lowenstein medium. But in fact, only isolation of the tubercle bacillus at the liver level confirms presence of tuberculosis. PMID- 4026197 TI - [Spontaneous rupture of the spleen during the development of chronic pancreatitis. One case]. AB - Spontaneous rupture of the spleen is a relatively rare occurrence during the course of chronic pancreatitis. The physiopathology remains imprecise and mechanical factors are associated with pancreatic enzyme diffusion and vascular changes in explaining its aetiology. The diagnosis is difficult since it often mimics an acute exacerbation of pancreatitis or even actual acute pancreatitis when the existence of the pancreatic condition is not previously known. Abdominal echotomography or peritoneal puncture-lavage and, now, CAT scanning are the key factors in reaching the diagnosis. PMID- 4026198 TI - [Culture of human hepatocytes. Findings and outlook]. AB - Human hepatocytes can be obtained by portal vein perfusion in the presence of collagenase. A co-culture system is suitable for maintenance of high levels of specific functions. The field for the use of cultured hepatocytes is now being enlarged. Pharmacological, carcinological and virological studies on a cellular scale are within the bounds of possibility. PMID- 4026199 TI - [Non-operative treatment of ulcer perforation]. AB - The treatment of perforated duodenal ulcer cannot be standardised. In emergency to treat definitively both the perforation and the peptic ulcer request selectionned patients. We think that in emergency the primary aim is the treatment of the perforation to save the patient's life. The non operative method (Taylor-Quenu) keeps reasonably its place in the treatment of perforated duodenal ulcer in spite of critical opinions. This method has not to be used in patients who are said inoperable. PMID- 4026201 TI - Energy balance study in Singapore medical students. AB - Energy cost of rest and various common daily activities was measured in 7 male and 16 female medical students by using a Max-Planck respirometer and a Lloyd's gas analysis apparatus. The average weight of male and female subjects during the course of the study was 67.3 +/- 14.2 and 51.2 +/- 5.1 kg, respectively. The average energy expenditure per day was estimated from a diary of activities for a period of 7 days. The average daily intake of energy was computed from food tables and based on weighed amounts of raw materials of food consumed over the same 7-day period when energy expenditure was determined. The average energy expenditure of rest and different activities was found to be significantly lower than the figures published for western subjects. The daily energy intake and expenditure were 2,138 +/- 217 kcal (9.0 +/- 0.9 MJ) and 1,894 +/- 168 kcal (8.0 +/- 0.7 MJ), respectively, in male medical students, giving a positive balance of 244 kcal (1.0 MJ). The values of the same in female medical students were 1,711 +/- 292 kcal (7.2 +/- 1.2 MJ) and 1,474 +/- 211 kcal (6.2 +/- 0.9 MJ) with a balance of 237 kcal (1.0 MJ). PMID- 4026200 TI - Disturbances of tryptophan metabolism in mice acutely deprived of tryptophan. AB - The effect of a dietary tryptophan deficiency on tissue serotonin (5 hydroxytryptamine) synthesis rates, systemic tryptophan metabolism and its response to steroid or cycloheximide treatment was investigated. Brain serotonin synthesis was depressed in tryptophan-deprived (TD) mice while duodenal serotonin synthesis was enhanced following a tryptophan load. Liver total protein content was initially depressed in TD mice but increased following a tryptophan load. Blood tryptophan and albumin were depressed in TD mice while the percentage of albumin-bound tryptophan significantly increased in TD mice. Serum-free fatty acids were not significantly altered. Furthermore, enzyme kinetics studies indicated that in TD mice, tryptophan-5-hydroxylase has a reduced Vmax, while the Km for both tryptophan and the pteridine cofactor was significantly lowered. The tryptophan hydroxylase response to tryptophan or hydrocortisone injection was accentuated in TD mice while the tryptophan-2,3-dioxygenase response to tryptophan or hydrocortisone injection was blunted in TD mice. Finally, injection of tryptophan and cycloheximide blocked the tryptophan-2,3-dioxygenase response while the tryptophan hydroxylase response was unaltered in both control and TD diet mice. PMID- 4026202 TI - Effect of dietary fats on experimental hypertension. AB - In an experiment on 95 Wistar rats weighing 330 g the effect was studied of partially hydrogenated marine oil and cod-liver oil as well as sunflowerseed oil and animal fat on arterial hypertension induced with administration of 1.5% NaCl in drinking water. During 5 weeks the animals received diets containing 37.8 kcal% derived from the studied fats. After the first week of 1.5% NaCl solution administration a significant rise of the systolic blood pressure and heart rate was observed in all animals without regard to the fat received by them with the diet. The rise of the blood pressure was greatest in the group of rats kept on the diet with animal fat, while in the groups of rats receiving diets with sunflowerseed oil or marine oils this rise was significantly smaller, especially with cod-liver oil. The hypotensive effect of marine oils, particularly cod-liver oil, was more pronounced than that of sunflowerseed oil. The hypotensive effect of partially hydrogenated fish oil was less pronounced than that of cod-liver oil. Our experiments demonstrated a significant effect of the amount of dietary fat on the development of experimental hypertension. Greater intake of salt and animal fats in human diet may be one of the causes of essential hypertension. PMID- 4026203 TI - Effects of iron supplementation on serum ferritin and other hematological indices of iron status in menstruating women. AB - Serum ferritin, hemoglobin, serum iron and transferrin iron-binding capacity were evaluated in 107 healthy female students. 21 women had a serum ferritin of 12 micrograms/l or less, corresponding to an exhaustion of body iron stores. After 1 month of iron supplementation, significant increase of hemoglobin concentration and decrease of total iron-binding capacity were observed. Mean serum ferritin had increased from 24 to 41 micrograms/l, and all women had a serum ferritin above 12 micrograms/l. 1 month after the end of the trial, serum ferritin fell significantly. This study points out the problem of serum ferritin reference values and the definition of normal iron stores in menstruating women. PMID- 4026205 TI - Effect of ethanol on liver triglycerides and fatty acid composition in the golden Syrian hamster. AB - In choice situations, the golden Syrian hamster shows a strong preference to drink an ethanol solution to water alone. Because of the known effects of ethanol on lipid metabolism, its effects on liver fatty acids were therefore studied in the hamster. After a period of 8 weeks during which hamsters had consumed water containing 10% ethanol (4 weeks) and then 15% ethanol (4 weeks), the liver was significantly increased in weight, an effect which was shown to be due to fat accumulation as triglyceride. The fatty acid composition of the liver triglycerides and phospholipids was altered such that monounsaturated fatty acids were very significantly increased and both n-6 and n-3 essential fatty acids were proportionally decreased. PMID- 4026204 TI - Effect of supplementing medium chain triglycerides with linoleic acid-rich monoglycerides on severely disturbed serum lipid fatty acid patterns in patients with cystic fibrosis. AB - 7 patients with cystic fibrosis, having serum lipids with fatty acid compositions (FACs) skewed in the direction of essential fatty acid deficiency, were given a mixture of medium chain triglycerides (MCTs) with linoleic acid-rich monoglycerides (LAMs) as food fat (about 1-1.25 g/kg body weight/day). Blood was sampled before and after a short period (4-11 days) of experimental fat feeding. The FACs of the serum triglycerides (TGs), cholesterol esters (CEs) and phospholipids (PLs) were determined before and after dietary treatment. Dietary treatment resulted in a significant increase of the previously reduced fraction of linoleic acid in all lipid classes. In TGs, the increase in the fraction of linoleic acid was accompanied by a reduction of the previously increased fraction of palmitoleic acid to normal values, by a reduction in the fraction of oleic acid to subnormal values and by an increase in the fraction of stearic acid which, however, remained normal. In PLs, the increase in the fraction of linoleic acid was accompanied by an increase in the fraction of dihomogammalinoleic acid which remained normal, however. In CEs, concomitant with the increase of the previously reduced linoleic acid fraction, there was a reduction of previously elevated palmitoleic and oleic fractions, the latter to a normal value. Thus, supplementing a MCT-containing diet with LAMs in cystic fibrosis patients results in a considerable amelioration of the previously disturbed FACs of the major serum lipid classes. PMID- 4026206 TI - [What can be expected of x-ray computed tomography in the assessment of the loco regional extension of kidney cancer?]. AB - The authors assess the role of CT scanning in investigations for the extension of renal tumors with the aid of a series of 40 patients. A complete inventory of the lesions was obtained in 30 patients who had undergone radical surgery. Capsular damage is visualized with a high percentage of uncertainty, and, setting aside a few exceptions, it is impossible to specify the histological nature of adenomegalies. On the other hand, venous exploration can be performed with growing accuracy thanks to series of angioscans. This method of investigation would therefore not seem suitable for staging tumors on Robson's scale, but it is most useful in selecting surgical tactics in the preoperative assessment of the lesions. PMID- 4026207 TI - [Microsurgical repair of the vas deferens. Apropos of 115 cases]. AB - The demand for the reversal of vasectomy in the treatment of sterility has been increasing over the past decade. Microsurgery is acknowledged to be the best non traumatic procedure for this reconstruction. This article reviews 115 patients treated by microvasovasostomy over a period of six years. Evaluation of the results shows 76% of patients with a positive seminal analysis, and 52% informed the authors that their partners were pregnant. In addition to the technical aspects (i.e. the non-traumatic manipulation of tissues using microsurgical procedures) the titer of antisperm bodies in the patient's serum and seminal plasma seems to play some part in the recovery of fertility. PMID- 4026208 TI - [Ureteral endometriosis. Apropos of a bilateral form]. AB - A case of bilateral ureteral endometriosis is reported. The patient presented, on one side, with endometriosis externa, associated with slight renal injury, and, on the other, with adenomyosis leading to uretero-ureteral invagination, and an associated severe renal impairment. A review of the reported cases and pathogenic theories is followed by a discussion of the diagnostic and therapeutic problems raised by ureteral endometriosis. The difficulty of establishing a correct diagnosis and the risk of damage to renal function often lead to surgical removal of the ureteral lesion. PMID- 4026209 TI - [Cecocystoplasty. Apropos of 14 cases]. AB - Cystoplasty is the ideal method of bringing back normal urinary flow after cystectomy, and the authors have used this procedure in fourteen cases. The cecum is mobIlized with its vascular pedicle. Bowel continuity is readily and safely restored with the aid of suturing forceps (TA 55, GIA). The cecum is carefully cleaned of all fecal matter. Two UCN join the ureters and the cecum, to which the trigone, the cervix vesicae, or the prostatic or membranous urethra is anastomosed, depending on the case. Three benign cystopathies, four recurrent diffuse papillomatoses and seven vesical carcinomas were treated in this way, with excellent results. PMID- 4026210 TI - [Topographic anatomy of the caliceal stem: the colonic risk]. AB - Body-section roentgenograms were taken of seventy five patients examined for non urological complaints. These were studied and the axes of the ventral and dorsal calices were measure. The axis of the ventral calix passes through the left or right colon. The axis of the dorsal calix follows the avascular line and passes to the lateral border of the paravertebral muscles, avoiding the left and right colon. These anatomical data confirm that the dorsal calix is the route of choice in the percutaneous approach to the kidney. PMID- 4026211 TI - [Analysis of 278 sphincterotomies of the urethral stria in 232 male patients]. AB - The authors report 278 external sphincterotomies performed on 232 male neurological patients, presenting with specific etiologies requiring surgery: vesico-ureteral reflux (33.6%), ureterohydronephrosis (18.9%), and spontaneous hyperreflexia (7.4%). The level of the spinal cord injury was superior to T8 in 32.3% of cases (double the corresponding figure for paraplegic patients) and inferior to L1 in 31.2% (25% more than for paraplegics). Short-term results are good in 70% of cases, in terms of dysuria and infection. Iterative sphincterotomy is required in 19.8% of cases, and surgery of the neck of the bladder is required in 34.8%. In the medium term, 83.7% of the good results show an improvement. Continence is achieved in 14.4%, and 12.2% of the patients are incontinent. The mortality rate was 1%, and 10% of the patients suffered from postoperative hemorrhage. Long-term results show 3.2% of secondary impotence, and 10% of patients requiring urinary diversion. PMID- 4026212 TI - [Cancer of the prostate revealed by hemospermia in a young man]. AB - The authors report a case of prostatic cancer in a 50-year-old patient, for which the sole clinical manifestation was recurrent hemospermia. There was an undoubted connection, in this case, between the hemospermia and the cancer, which is rare. The treatment was endoscopic associated with cobalt therapy. The follow-up is four years. PMID- 4026213 TI - [Urinary incontinence following prostatectomy. Results of cervico-urethral plasty using Tanagho's tubular vesical flap]. AB - Seven patients suffering from urinary incontinence after prostatectomy were treated by cervico-urethral plasty with a tubular vesical flap. Results were good or very good in four cases, and fairly good in one. There were two setbacks. The procedure should be reserved to patients not afflicted with vesical instability, cervico-urethral obstruction or fibrosis of the anterior surface of the bladder. Patients suffering from the last two conditions require an artificial sphincter after removal of the obstructive lesions. PMID- 4026214 TI - [Cancer of the bladder. Importance of the assessment of lymph node involvement in the selection of therapy]. PMID- 4026215 TI - [Vascular access lines: use of biologic grafts]. AB - To ensure vascular access, a biological graft was inserted in 44 patients from August 1982 to February 1985 at the Department of Urology, Pitie Hospital, Paris. Forty-nine grafts were used, including 39 saphenous veins and 10 carotid arteries from calves. Four patients free of renal failure had insertion of a graft to allow chemotherapy (3 cases) or plasmapheresis (1 case). Graft patency rate in these four patients is 50%. Among the 40 patients with renal failure, 11 have not yet had dialysis, 26 are currently under dialysis, 2 have been lost to follow up, and 1 died before dialysis. All but one of the patients with renal failure not treated by dialysis have a patent graft. Graft patency rate after one year in the 26 patients under dialysis is 83% for non-reoperated patients and 91% for reoperated and non-reoperated patients as a group. As concerns complications, an interesting fact is that thrombosis of the graft usually required graft replacement, whereas most delayed stenoses were treated by surgery with preservation of the graft. No case of infection or aneurysm was recorded throughout follow up. These results pertain chiefly to saphenous vein grafts as use of carotid arteries from calves is recent. In view of the 95% immediate graft patency rate and of the satisfactory results at one year in these patients usually selected because of the poor condition of accessible arteries and veins, we believe biologic grafts constitute an outstanding material in vascular access surgery for hemodialysis. PMID- 4026216 TI - [Urethroplasty in severe hypospadias. Description and evaluation of a one-stage technic used in 54 cases]. AB - From July 1980 to November 1982, 54 cases with severe hypospadias underwent one stage urethroplasty at the urology departments of the Ain Shams University Hospital and Dar El-Shefa Hospital. Their age ranged between 9 months and 19 years. The original urethral meatus was located at mid penile in 40 occasions, peno-scrotal in 12 and perineal in only two cases. The technique used for urethroplasty was a combination of that of Duckett (transverse preputial island flap) for the creation of the urethral tube, and Devine's glandular flaps to bring the urethral meatus to the tip of the glans. The rate of complications was very low, only two cases developed fistula (3.7%). None of the cases developed kinks or strictures of the neo-urethral tube. PMID- 4026217 TI - [Hydraulic penile prostheses in the surgery of impotence. Our experience in 20 cases with a 2-year follow-up]. AB - The authors report their experience of the implantation of inflatable penile prostheses in the surgical management of impotence. They have implanted twenty prostheses with a followup of two years to three months. The overall results are very satisfactory in terms of the quality of the sexual life of the couple (85%). On the other hand, the postoperative morbidity rate is high, with 40% of complications including 20% requiring reoperation. PMID- 4026218 TI - [Pelvic hematomas of prostatic origin]. AB - Two cases of pelvic hematoma following prostatic biopsy and prostatic massage are reported. They are rare complications of very common urological acts. The diagnosis, treatment and prevention of these complications are discussed. PMID- 4026219 TI - [Vulvar cysts disclosed in a neonate. Apropos of 6 cases]. AB - The authors report six cases of vulvar cysts in female neonates. Careful examination of the vulva normally leads to correct diagnosis of this rare lesion, but a few additional examinations may be helpful. Simple puncture without anesthesia is generally sufficient for a successful treatment of this benign and isolated tumor. The authors go on to discuss the embryological, histological and histochemical aspects, and review the literature. PMID- 4026220 TI - [Use of the great epiploon in the treatment of complex vesico- and urethro vaginal fistulae]. AB - The omentum was used in the treatment of seven patients presenting with complex vesicovaginal fistulae, and three patients with urethrovaginal fistulae. The operation was immediately successful in all cases. The three patients with urethrovaginal fistulae subsequently suffered from stress incontinence, which was treated by a sling operation three months later. PMID- 4026221 TI - [Perioperative ureteroscopy]. AB - Is endoscopy of any use for ureteral exploration during open surgery of the upper urinary tract? This article sets out to answer the question with the aid of three cases, and discusses the indications in the light of current developments in transurethral and translumbar ureteroscopy. PMID- 4026222 TI - [Continuous peridural morphine analgesia in refractory pain in urology]. AB - Peridural catheterization connected to a sub-cutaneous morphine reservoir can provide an effective and prolonged analgesia for certain pelvic pains of a urological origin which resist the usual sedative therapies. The authors describe the method of catheterization and the results which they have obtained in five patients treated in this way. PMID- 4026223 TI - [Cancer of the colon following ureterosigmoidostomy or following bladder enlargement using a colonic graft]. AB - The role of carcinogenic factors following urinary diversion are here studied on the basis of three very different cases. In the first, an adenocarcinoma developed at the site of a ureterocolic anastomosis thirty one years after Coffey's operation for bladder exstrophy. In the second, the tumor had developed, 31 years after uretero-sigmoidostomy, for ureteral trauma. The anastomosis had moreover ceased to function ten years previously. In the third case, the patient had undergone a right nephrectomy for urinary tuberculosis and a colocystoplasty to enlarge the bladder with re-implantation of the left ureter in the graft. Twenty one years later, an adenocarcinoma developed at the site of the anastomosis between the colonic graft and the bladder. This was an exceptional case (possibly the first) of a cryptal tumor developing out of contact with material. It thus runs counter to the alleged role of facies in the development of adenocarcinomas following urinary diversion. PMID- 4026224 TI - Human telencephalic angiogenesis. AB - We provide new observations regarding the histogenesis and regional development of the human telencephalic microvasculature during the last half of gestation. Endothelium-lined trunks extending from pia to the subventricular plexus, evident early in gestation, persist during the last half of gestation. The courses of these trunks are modified and become complex as the bulk of the telencephalon, striatum, and thalamus increases and as gyri grow. New cerebral tissue is supplied by increasing numbers of shorter penetrating vessels. All extrastriatal vessels have many lateral right- and acute-angle branches that join nearby trunks and shorter vessels. Striatal vessel branches predominantly have acute angles. Most extrastriatal channels remain devoid of apparent muscularis until the final weeks of gestation. In contrast, striatal arteries begin to muscularize at about 24 weeks of gestation. Muscularization appears to occur in a centripetal direction and is apparent in the caudate at approximately 30 weeks' gestation. We did not identify transventricular, paraventricular, or recurrent arteries ending in deep white matter. PMID- 4026225 TI - The critical role of Wernicke's area in sentence repetition. AB - The anatomical correlates of persistent deficits in sentence repetition were studied in a group of 32 right-handed patients with fluent aphasia caused by left hemisphere ischemic stroke. Patients whose ability to repeat remained impaired by 6 months after onset almost without exception had damage to Wernicke's area. Furthermore, all patients with damage to Wernicke's area had impaired repetition 6 months after onset. The most consistent lesion correlating with chronic impairment of repetition, therefore, was one destroying parts or all of Wernicke's area. Lesions outside of this area typically resulted in milder impairment of repetition that resolved within a few months. Only 5 patients had no repetition impairment when tested early (1 month after onset). These patients all had lesions anterior to the rolandic fissure, some including Broca's area. PMID- 4026226 TI - Nucleus tractus solitarius lesions elevate pulmonary arterial pressure and lymph flow. AB - The effects of lesions of the nucleus tractus solitarius (NTS) on pulmonary vascular pressure and pulmonary lymph flow were investigated in 6 halothane anesthetized sheep. After lesions of the NTS were created using bilateral thermocoagulation, pulmonary artery pressure rose to 150% of baseline and remained elevated for the 3-hour duration of the experiment. Systemic and left atrial pressures did not change. Pulmonary lymph flow doubled within 2 hours; the lymph-plasma protein ratio was unchanged from baseline. Sham NTS lesions and lesions lateral to NTS produced no changes. These experiments demonstrate that lesions of the central nervous system can alter pulmonary vascular pressures and transcapillary fluid flux independently of effects upon the systemic circulation. These findings may have relevance for the understanding of neurogenic pulmonary edema in humans. PMID- 4026227 TI - Postoperative contrast enhancement in patients with brain tumor. AB - Contrast enhancement resulting from surgical trauma may mimic residual enhancing tumor, thereby complicating the interpretation of postoperative computed tomographic scans. We assessed the natural history of postoperative enhancement in 10 patients with brain tumor. Contrast enhancement distinguishable from residual enhancing tumor appeared along the operative margin following tumor resections but not lobectomies. Enhancement appeared as early as the fifth postoperative day, was most intense at two weeks, and persisted for several months. Prior to the fifth postoperative day, enhancement reflected residual tumor. Edema and artifacts were more prominent on the first and second postoperative days than on the third and fourth. We recommend that postoperative computed tomographic scans to assess residual enhancing tumor be performed on the third or fourth postoperative day. This timing avoids postoperative enhancement and minimizes interpretative difficulties caused by artifacts. PMID- 4026228 TI - Nucleus raphe dorsalis in Alzheimer's disease: neurofibrillary tangles and loss of large neurons. AB - Diffuse serotonergic fibers are presumed to project to the telencephalon from the nucleus raphe dorsalis (NRD) of the midbrain, in a manner similar to the cholinergic projections from the nucleus basalis of Meynert (nbM) to the cerebral cortex. Neuropathological changes in both of these nuclei have been reported in Alzheimer's disease (AD). Although many morphometric studies of the nbM in AD have been documented, only one such study of the NRD has been conducted so far; it demonstrated a sixfold increase in neurofibrillary tangles in AD but no statistically significant difference in the number of neurons in patients with AD and age-matched controls. A study of the NRD utilizing different stains and wider anatomical boundaries is detailed in this report of 5 patients with AD and 7 age matched controls. In AD the NRD showed 39 times more neurofibrillary tangles and the number and cell density of large neurons were reduced to 23% and 28%, respectively, of those in the controls. A small number of senile plaques were found in the NRD in all patients with AD but none were found in the controls. PMID- 4026229 TI - The influence of preexisting oscillations on the binocular optokinetic response. AB - Full-field binocular optokinetic responses were examined in patients with congenital nystagmus. If the stimulus moved in the same plane as the congenital nystagmus, a gaze-modulated response was recorded for both idiopathic and albino observers. When the congenital nystagmus was almost totally suppressed, neither a gaze-evoked nor a sawtooth response was seen. For stimulus movements in a plane orthogonal to the congenital nystagmus, normal sawtooth optokinetic responses were exhibited by both groups. Experimental evidence supports the hypothesis that the optokinetic response in the meridian of the spontaneous oscillation has been adapted. PMID- 4026230 TI - Leptomeningeal metastases: peripheral nerve and root involvement--clinical and electrophysiological study. AB - Twenty-five patients with recently diagnosed leptomeningeal metastases underwent a prospective clinical and electro-physiological study to assess the mode and extent of peripheral nerve and spinal root involvement. Motor conduction velocities and F wave latencies in the legs were found frequently to be disturbed compared with normal subjects and a control group of cancer patients. F wave changes were the most sensitive indicator of root involvement. Electrophysiological abnormalities were detected in 20 patients, compared with 15 who had abnormal clinical signs suggesting peripheral nerve dysfunction. Electrophysiological studies can be useful in the evaluation of patients with suspected leptomeningeal metastases, and repeated recording of F wave latencies may serve to indicate root recovery in a clinically stable patient. PMID- 4026231 TI - Balo's concentric sclerosis: new observations on lesion development. AB - A 54-year-old woman with a four-month history of progressive neurological illness was found at postmortem examination to have lesions of Balo's concentric sclerosis. Balo lesions were found in several areas scattered widely throughout the central nervous system, including the spinal cord, a previously unreported location, and were studied by histological and ultrastructural methods. Balo lesions consisted of bands of intact myelin alternating with zones of demyelination. These lesions were centered on a perivascular cuff of inflammatory cells. The center of the lesion was the oldest area with the concentric rings of demyelination decreasing in age with increasing distance from the center. The bands of intact myelin comprised mainly remyelinated fibers, were similar to those seen at the edges of chronic active multiple sclerosis plaques, and may have represented the repaired margins of preceding episodes. The occurrence of small foci of acute demyelination centered on perivascular cuffs and other changes typical of both acute and chronic active multiple sclerosis may indicate that the lesion of Balo's concentric sclerosis represents an intermediate stage in the development of an established multiple sclerosis lesion. PMID- 4026232 TI - Information processing speed in Friedreich's ataxia. AB - Three patients with Friedreich's ataxia and six controls matched by age and vocabulary and information scores on the Wechsler Adult Intelligence Scale Revised were administered a measure of short-term memory scanning. Patients with Friedreich's ataxia demonstrated a deficit in information processing speed in the relative absence of impairment in attention, memory, language, judgment, reasoning, and other cognitive functions. The short-term memory scanning procedure may be useful in documenting cognitive slowing and in distinguishing this impairment from the motor abnormality often associated with a subcortical brain disorder. PMID- 4026233 TI - Hyperbaric oxygenation does not improve multiple sclerosis. PMID- 4026234 TI - Transverse myelopathy in progressive systemic sclerosis. PMID- 4026235 TI - Encephalopathy associated with baclofen. PMID- 4026236 TI - CT evaluation in patients after first seizure. PMID- 4026237 TI - Lithium-induced visual hallucinations: evidence for possible opioid mediation. PMID- 4026238 TI - Hemiplegic migraine and progressive hemifacial atrophy. PMID- 4026239 TI - Increased head circumference in patients with Duchenne muscular dystrophy. PMID- 4026240 TI - Multi-dimensional complexes of skull traits. AB - The simultaneous incidence of sutural bones was studied by a multidimensional analysis (Wanke method). On a medieval sample of 249 male and female skulls from Lower Austria the presence of two main complexes of sutural and fontanelle bones was observed. The interaction of possible genetic factors and developmental growth incongruences in causing these phenomena are discussed. The necessity of further studies considering such basic biological aspects with minor skeletal traits is stressed. PMID- 4026242 TI - Palmar creases in Spaniards. AB - In a sample of Spanish people (403 males and 513 females) the palmar creases have been studied according to the method of Bali & Chaube (1971). Bimanual differences are not statistically significant, but there is a sexual dimorphism. Comparing the incidence of the open M type defined by Tillner there are no statistical differences as compared with male German series, though they are seen in female series. It is observed that the frequency of the simian crease is in accordance with the variability of European populations. PMID- 4026241 TI - Anthropometric study of male external genitalia of 320 healthy Nigerian adults. AB - Five basic measurements of the male external genitalia were studied in 320 healthy male medical students belonging to the various parts of Nigeria (West Africa). Their ages range from 17 to 23 years. The measurements were as follows: average length of the penis (81.6 +/- 0.94 mm); circumference of the penis (88.3 +/- 0.02 mm); circumference of the scrotum (212.6 +/- 2.48 mm); length of right testis (46.8 +/- 0.54 mm); width of right testis (32.4 +/- 0.37 mm); length of left testis (46.0 +/- 0.53 mm); and width of left testis (31.4 +/- 0.36 mm). The size of the genitalia increases with the increase in age in younger year groups. The adult stages of genitalia development are reached at the age of 21 years in 89.0% of the individuals. The growth of the genitalia is continued with the increasing height and weight, but this growth slows down after attaining a definite height and weight. PMID- 4026243 TI - [Experimental study of vibration agitation in antibiotic biosynthetic processes in laboratory apparatus]. AB - The use of vibroagitation in biosynthesis of antibiotics was shown to be in principle possible. The results of the experiments in 3-liter apparatus equipped with devices for vibroagitation and turbine mixers are presented. PMID- 4026245 TI - [Hydrodynamic study of a centrifugal differential-contact extractor]. AB - Centrifugal extractors of the differential-contact type are widely used all over the world in production of antibiotics. Lately, new extractors were developed by Hitachi (Japan). Model E is of a special interest. In the present study the values of the working zone of the Hitachi extractor, EP-02 Ultrex were determined by the pressure levels and the effect of the main parameters characterizing the apparatus hydrodynamic conditions on the minimum and maximum critical pressure was estimated. The results of the study provide wide variation of the hydrodynamic parameters in determination of the most rational extraction conditions. PMID- 4026244 TI - [Regulation of heliomycin biosynthesis by the carbon source]. AB - The effect of different carbon sources on the biosynthesis of heliomycin by Streptomyces olivocinereus 11-98 was studied. Inverse relationship between the culture growth rate and the biosynthesis of heliomycin in the media with different sugars was shown. Arabinose and glucose provided the highest culture growth rate, while the levels of the antibiotic biosynthesis were the lowest. With the use of lactose the culture growth rate was the lowest and the antibiotic biosynthesis level was the highest. The level of the antibiotic biosynthesis was determined not only by the culture growth rate but also by the nature of the carbon source. With the use of glucose repression of heliomycin biosynthesis was much lower than that with the use of arabinose, while the culture growth rates were similar. Addition of glucose to the medium with lactose resulted in increasing of the antibiotic biosynthesis as long as the glucose concentration in the medium increased. Glycerol proved to be the most favourable carbon source for the biosynthesis of heliomycin. It also provided a comparatively high rate of the culture growth. Arabinose inhibited the antibiotic synthesis in the medium with glycerol and the inhibition level rose with an increase in the arabinose concentration. It is suggested that regulation of heliomycin biosynthesis is of the "glucose effect" type. PMID- 4026246 TI - [Comparative evaluation of several noninstrumental methods of determining fats in the fermentation media in manufacturing antibiotics]. AB - The use of instrumental analysis (IR spectrometry, high performance liquid chromatography) for determination of fats in the nutrient media and fermentation broths in antibiotic production is not efficient. 7 noninstrumental methods for determination of fats in the fermentation broths of some fat-soluble polyester antibiotics were compared. The first method includes extraction of the fermentation broth with different agents, gravimetric estimation, measuring of the saponification number and refraction coefficient and thin-layer chromatography. It was shown that determination of the saponification number after extraction with alkanes or diethyl ether provided reliable results. Thin layer chromatography can be used as a rapid method. PMID- 4026247 TI - [Immunochemical study of blastolysin]. AB - The immunochemical properties of blastolysin (BL), a preparation obtained from the cell walls of Lactobacillus bulgaricus with immunostimulating and antitumor activity were studied. The experiments on dogs and rabbits showed that the immunogenic effect of BL was not high. However, after parenteral administration to the dogs and rabbits it induced production of the specific antibodies detected with the Ouchterlony test of direct hemagglutination and immunodiffusion. This should be taken into account in development of the schemes for its use as a pharmacological agent. With the procedures of gel filtration on the columns with Sephadex G-75 and immunodiffusion the fraction composition of BL was determined and the use of the immunochemical procedures for standardization of the BL preparations was shown to be possible. PMID- 4026248 TI - [Molecular mechanism of oxacillin interaction with human serum albumin studied by microcalorimetry]. AB - Interaction of oxacillin, a semisynthetic penicillin, with human serum albumin (HSA) was studied by means of reaction isothermal and differential scanning microcalorimetry. The antibiotic bound with one primary and two secondary active protein sites. The first bound molecule of the drug had a significant effect on conformation of the biopolymer, which was evident from increased enthalpy and denaturation temperature of the complex as compared to pure HSA. However, the increased thermostability of the serum albumin on its association with oxacillin did not impair the cooperative nature of the thermal denaturation of globular protein. Analysis of the thermodynamic parameters of the complex formation suggested the presence of hydrophobic and electrostatic interactions. The role of electrostatic interaction increased with a decrease in the solution ionic strength. PMID- 4026249 TI - [Comparative evaluation of the myelotoxic action of rubomycin, adriamycin and carminomycin by their delayed effects in an experiment]. AB - The experiments were performed on intact noninbred rats and BALB/c mice with the use of different models of the hemopoiesis compensatory-functional tension and the morphofunctional methods. It was shown that at the period of complete recovery of the morphological composition of the peripheral blood 30 days after discontinuation of the 10-day course of daily administration of rubomycin, adriamycin and carminomycin in equivalent doses (1/10 of the LD50) pronounced inhibition of hemopoiesis was preserved in the animals. This could not be detected with the routine methods used for investigation of the cell homeostasis and was evident from limited compensatory reactions of granulocytopoiesis and erythropoiesis under conditions of additional action on hemopoiesis. PMID- 4026250 TI - [Inactivation of the inductor virus (Newcastle disease virus) during the isolation of porcine leukocyte interferon]. AB - The use of the routine method for inactivation of the inductor virus by acidification of interferon to pH 2.0 resulted in a significant decrease in the antiviral activity of pig leukocytic interferon, since the preparation was highly sensitive to changes in the pH values. The use of 0.1 per cent solution of formalin provided complete inactivation of the virus. The antiviral activity of interferon treated with formalin was on an average 5 times higher than that of the preparation incubated at pH 2.5-2.6. Precipitation of pig interferon with polyethylene glycol promoted both increasing of the titers of the antiviral activity of the preparation and elimination of the formalin residues from it. Interferon prepared with this procedure was not toxic in tissue cultures, had no side effects when applied to the eye mucosa and was absolutely harmless when administered to animals. It was shown that inactivation of the inductor virus with formalin was in principle possible in human leukocytic interferon. PMID- 4026251 TI - [Pharmacokinetics of the new antitumor antibiotic reumycin in an experiment: the prediction of the human pharmacokinetic profiles]. AB - The reumycin pharmacokinetics was studied with HPLC on Wistar rats after intravenous injection of the antibiotic in single doses of 2.5, 5 and 10 mg/kg and after its oral administration in single doses of 5 and 10 mg/kg. It was shown that the reumycin pharmacokinetics within the above dose ranges was nonlinear and within every dose could be described by a two-compartmental model. Its nonlinear nature might be associated with saturated binding of the antibiotic by the blood serum proteins. The absolute extent of the reumycin bioavailability after oral administration was 50 per cent. The variability of the reumycin cumulative renal excretion was due to bimodality of distribution of the parameter in the animals. Renal excretion of the intact antibiotic decreased from 35 to 20 per cent with increasing of the dose. The value of the reumycin half-life in humans was predicted (41-46 hours) with the pharmacokinetic animal scale-up. PMID- 4026252 TI - [The reactions of aminoglycoside antibiotic interaction with organic reagents]. PMID- 4026253 TI - [Characteristics of the process of regulated biosynthesis of oxytetracycline]. AB - Investigation of the process of oxytetracycline biosynthesis in a model medium showed that addition of maltose during the phase of antibiotic biosynthesis resulted in an increase in the rate of the culture growth, prolongation of the antibiotic production phase and increased productivity of the mycelium. The productive mycelium was characterized by a higher content of total nitrogen and phosphorus. PMID- 4026254 TI - [Effect of levorin and its combination with a modifying factor on the fatty acid composition of Crithidia oncopelti lipids]. AB - It was shown by us earlier that the sensitivity of Crithidia oncopelti to levorin, a polyene antibiotic, increased in the presence of sodium acetate as a modifying factor. A simultaneous change in the ratio of C. oncopelti structural lipids was also observed. The present paper deals with investigation of the effect of levorin and its combination with the modifying factor on the fatty acid composition of C. oncopelti lipids. The study showed that addition of sodium acetate in a concentration of 40 mg/ml to the medium for cultivation of C. oncopelti resulted in an increase in the total level of fatty acid unsaturation at the expense of a significant increase in the content of linoleic acid and polyunsaturated acids. The content of monoene fatty acids simultaneously decreased. In a concentration of 1 microgram/ml levorin had no effect on the growth of C. oncopelti and did not practically change the relative content of its fatty acids. Combined addition of levorin (1 microgram/ml) and sodium acetate (40 mg/ml) to the medium resulted in inhibition of the culture growth by 60-80 per cent and a marked increase in the total content of saturated acids with a decrease in the level of monounsaturated and polyunsaturated acids. The trypanostatic concentration of levorin (10 micrograms/ml) had the same effect and also lowered the total level of unsaturated fatty acids of C. oncopelti.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4026255 TI - [Pharmacokinetics of sisomicin during hemosorption and hemodialysis]. AB - The effect of hemosorption and hemodialysis on the pharmacokinetics of sisomicin was studied in 17 patients with acute and chronic renal insufficiency. The value of the antibiotic extraction coefficient in hemosorption was almost 2 times higher than that in hemodialysis. In patients on hemosorption, extracorporeal elimination of the antibiotic was of the saturation nature. It was characterized by systematic diminishing of the extraction coefficient, while in patients on hemodialysis, it did not depend on the time (the value of the extraction coefficient was constant). In this connection it is recommended that the rate of diminishing of the extraction coefficient in hemosorption be estimated. Since sisomicin is rapidly absorbed by the column it is not advisable to administer sisomicin to patients before hemosorption. PMID- 4026256 TI - [Experimental study of the pharmacological properties of amikacin]. AB - The general toxic and organotropic properties of amikacin were studied in acute and chronic experiments. The antibiotic was administered to the experimental animals in the doses equivalent to the therapeutic ones for humans or exceeding them 2-3 times. No unfavourable effect of amikacin in the above doses on hearing was observed. A certain increase in the level of urea nitrogen in the blood serum and leukopenia were registered only after administration of the highest drug dose exceeding 2 times the equivalent treatment dose of amikacin for humans (15 g). After the use of this dose separate microfocal necrotic lesions were detected morphologically in the proximal tubules of the kidneys. The lesions were of a transitory nature. It is concluded that amikacin has a wide range of therapeutic doses and the level of its safety is rather high. PMID- 4026257 TI - [Experimental multifactorial study of the effect of doxycycline and glucosaminylmuramyl dipeptide on the primary immunologic response to antigens of a tularemia vaccine strain]. AB - The effect of the combined use of doxycycline and glucosaminylmuramyl dipeptide (GMDP) on the primary immune response to antigens of tularemia vaccine was studied on CBA male mice with the use of the multifactorial design of experiment. Antibodies to the blood serum of the immunized animals were determined by the passive hemagglutination test with the use of the tularemia antigen diagnosticum. The delayed type hypersensitivity was estimated by changes in the weight of the extremities of the experimental and control animals treated with the antigen and saline solution, respectively. The multifactorial experiments provided precise quantitative characteristics of the optimal dose-time schedule for the combined use of GMDP and doxycycline. PMID- 4026259 TI - [Antibiotic sensitivity of microorganisms isolated from urine in exacerbations of chronic pyelonephritis]. PMID- 4026258 TI - [Possibility of increasing the efficacy of antibiotic therapy of erysipelas using combinations of methyluracil with prodigiozan]. AB - Two hundred and six patients with erysipelas were examined. Of these, 100 patients were subjected to the routine therapy and 106 were additionally treated with methyluracil and prodigiosan. It was noted that the use of methyluracil and prodigiosan in the combined treatment of erysipelas promoted an increase in the efficacy of the antibiotic therapy owing to acceleration of the local inflammation regression and the favourable effect of the treatment on the cell immunity. PMID- 4026260 TI - [Pharmacokinetics of ampicillin in patients with chronic renal insufficiency during hemodialysis and hemosorption]. AB - It was shown that when the filtration capacity of the kidneys was lowered even insignificantly (the creatinine clearance 50-80 ml/min), the maximum blood levels of ampicillin increased 2 times and its retention time was prolonged. At the terminal stage of chronic renal insufficiency the half-life of the drug and the area under the pharmacokinetic curve markedly increased and the plasma clearance decreased. Hemodialysis and hemosorption significantly lowered the ampicillin half-life. The ampicillin coefficient in hemosorption was 2 times higher than that in hemodialysis. PMID- 4026261 TI - [Use of ampicillin in treating inflammatory diseases of the bile ducts]. PMID- 4026262 TI - Inducible phenotypic multidrug resistance in the fungus Mucor racemosus. AB - The dimorphic fungus Mucor racemosus exhibited a single-step, inducible resistance to cycloheximide, trichodermin, and amphotericin B. Cells adapted to inhibitory levels of the antibiotics after 12 to 40 h. The adaptation involved all the cells in the population and was not the result of the selection of resistant mutants. Adaptation to one drug provided cross resistance to other, dissimilar drugs. Resistance was lost within several generations of growth in the absence of the inhibitors. PMID- 4026263 TI - Attenuation of experimental tobramycin nephrotoxicity by ticarcillin. AB - It is well known that in vitro the combination of carbenicillin, ticarcillin, or other antipseudomonal penicillins with gentamicin, tobramycin, or other aminoglycoside antibiotics results in the inactivation of the antibacterial activity of the aminoglycoside. To assess the influence of the in vivo interaction of tobramycin and ticarcillin on experimental nephrotoxicity, male Fischer 344 rats were given either tobramycin alone (120 mg/kg per day), tobramycin (120 mg/kg per day) and ticarcillin (250 mg/kg per day) concomitantly, or the combination of these drugs at the same doses that had been preincubated for 24 h and at the time of delivery contained but 63 and 25%, respectively, of the initial concentrations of tobramycin and ticarcillin as measured by conventional analytical procedures. Initial experiments were conducted to determine the concentrations of the antibiotics in serum achieved after administration of each test solution. After a single dose of the test solution, ticarcillin concentrations in serum were higher and more prolonged in rats given tobramycin plus ticarcillin than in rats given ticarcillin alone. After 7 days of exposure to the test solutions, inulin clearance in animals given tobramycin alone was 0.15 +/- 0.1 (mean +/- 2 standard errors) ml/min per 100 g of body weight as compared with 0.53 +/- 0.1 in rats given tobramycin and ticarcillin concomitantly, 0.59 +/- 0.1 in animals given the partially inactivated tobramycin ticarcillin mixture, and 0.79 +/- 0.1 in control rats. Although there was some improvement in inulin clearance in the group containing tobramycin alone, the three treatment groups maintained the same rank relationship in inulin clearance through 14 days of treatment. Real histology confirmed the attenuation of tubular injury in animals given tobramycin and ticarcillin concomitantly. There was no evidence of toxicity from the presumed inactivation complexes of tobramycin ticarcillin. These results document an in vivo protective effect of ticarcillin on experimental tobramycin nephrotoxicity. PMID- 4026264 TI - Enhanced efficacy of liposome-encapsulated ribavirin against Rift Valley fever virus infection in mice. AB - Administration of liposome-encapsulated ribavirin to mice led to ribavirin concentrations in the liver, the primary site of Rift Valley fever virus proliferation, that were fivefold greater than those attained with the same doses of free ribavirin. Liposomal ribavirin given at a dose of either 25 or 50 mg of drug per kg of body weight protected mice against a rapidly lethal high-titer challenge with Rift Valley fever virus, whereas similar doses of free drug or empty liposomes had no detectable benefit. Hence, tissue targeting of ribavirin with liposomes substantially increased the therapeutic index by increasing the efficacy of the treatment. By using liposomes as drug carriers, a nontoxic, low dose regimen of ribavirin had a therapeutic effect that was comparable to that achieved with higher but potentially more toxic doses of free ribavirin. PMID- 4026265 TI - Concentrations of fusidic acid, cloxacillin, and cefamandole in sera and atrial appendages of patients undergoing cardiac surgery. AB - The concentrations of cefamandole, cloxacillin and fusicid acid were measured in the serum and heart tissue of 100 recipients of these drugs before cardiac surgery. During cardiopulmonary bypass, mean (+/- standard deviation) peak concentrations in serum of all patients were 63.0 +/- 34.0 micrograms of cefamandole per ml, 30.8 +/- 17.7 micrograms of cloxacillin per ml, and 32.4 +/- 10.8 micrograms of fusidic acid per ml. Mean (+/- standard deviation) concentrations in atrial appendages taken 1 h (+/- 15 min) after infusion were 21.3 +/- 11.0 micrograms of cefamandole per g, 23.8 +/- 17.3 micrograms of cloxacillin per g, and 10.7 +/- 4.2 micrograms of fusidic acid per g. No cloxacillin could be detected in 5 of 39 heart specimens. Mean tissue-to-serum ratios at 1 h for cefamandole, cloxacillin, and fusidic acid were respectively 0.35, 0.73, and 0.33. Fusidic acid, a drug which is highly effective in vitro against both methicillin-resistant Staphylococcus aureus and Staphylococcus epidermidis, was detectable in heart tissue in concentrations which were 12 times higher than the MICs of this agent against these resistant microorganisms. PMID- 4026266 TI - Antimicrobial susceptibility patterns and R plasmid-mediated resistance of the fish pathogen Yersinia ruckeri. AB - Fifty strains of Yersinia ruckeri, the causative agent of enteric redmouth disease of salmonid fish, were tested for susceptibility to 23 antimicrobial agents by using an agar dilution procedure. The MICs were generally uniform for all serological varieties. Two of the 50 strains carried a 36-megadalton plasmid which determined resistance to tetracyclines and sulfonamides and was transferable to both Escherichia coli and Y. ruckeri recipients. The serovars did differ in their response to polymyxin B. Strains of serovars II, III, and V were highly resistant (MICs of 128 to 512 micrograms/ml), whereas most serovar I strains were susceptible to less than or equal to 2.0 micrograms/ml. Of 33 serovar I strains, 6 were highly resistant to polymyxin B, which is a characteristic that may divide serovar I (Hagerman) strains into two distinct subgroups. PMID- 4026267 TI - Inhibition of Chlamydia trachomatis growth in McCoy, HeLa, and human prostate cells by zinc. AB - Zinc salts (10(-4) and 10(-5) M) inhibited the number of Chlamydia trachomatis inclusions in McCoy, HeLa, and primary human prostate epithelial cell cultures. Addition of zinc salts 1 h before or 24 h after inoculation with C. trachomatis was found to inhibit growth. Both C. trachomatis serotype D and a lymphogranuloma venereum strain were inhibited by the zinc salts. Although the mechanism of inhibition is not known, the continued presence of the zinc appeared necessary for maximal effect. At the concentrations tested, zinc was not directly toxic to the McCoy cells. These results suggest that the levels of zinc in prostatic secretions may be sufficient to preclude the recovery of chlamydia in the diagnostic laboratory or to inhibit chlamydia from infecting the prostate in vivo. PMID- 4026268 TI - In vitro activity of cefbuperazone and other antimicrobial agents against isolates from the female genital tract. AB - Cefbuperazone (BMY 25182), a new cephamycin, showed activity similar to those of moxalactam and other cephalosporin-cephamycins against aerobic and anaerobic bacteria from female genital tract infections. MICs of the antimicrobial agents were less than or equal to 16 micrograms/ml for greater than 97% of organisms tested. All of the anaerobic bacteria tested were susceptible to clindamycin, metronidazole, and chloramphenicol. PMID- 4026269 TI - Activity of a peptidyl prodrug, alafosfalin, against anaerobic bacteria. AB - Alafosfalin, an antibacterial phosphonodipeptide requiring peptide transport for activity, was tested for activity against clinical strains of anaerobic bacteria in peptide-free Roche Sensitivity Test Medium no. 5 agar. It was active against Bacteroides spp., Fusobacterium nucleatum, and Clostridium perfringens but not against Clostridium difficile. Alafosfalin activity was antagonized by appropriate peptides. Synergy was obtained with other cell wall-active antibiotics. PMID- 4026270 TI - Systemic absorption and persistence of tioconazole in vaginal fluid after insertion of a single 300-mg tioconazole ovule. AB - After vaginal insertion of a 300-mg ovule of tioconazole in 10 patients with vaginal candidiasis, the mean concentration in plasma was 21.2 ng/ml (range, 10.6 to 35.8 ng/ml) at 8 h and was not measurable at 24 h in 9 of 10 patients. The mean vaginal concentration at 24 h was 21.4 mg/liter (range, 2.4 to 50 mg/liter) and remained detectable in 7 of 9 and 2 of 9 patients after 48 and 72 h, respectively. PMID- 4026271 TI - Comparative in vitro activities of selected antimicrobial agents against Edwardsiella tarda. AB - MICs of 14 antimicrobial agents for 29 strains of Edwardsiella tarda were determined by an agar dilution method. Of the agents tested, ciprofloxacin, enoxacin, and norfloxacin were the most active on a weight basis. All strains were also susceptible to clinically achievable concentrations of ampicillin, chloramphenicol, tetracycline, trimethoprim, sulfamethoxazole, trimethoprim plus sulfamethoxazole, cefotaxime, and gentamicin. Ninety percent of the strains demonstrated high-level resistance to polymyxin B and colistin. PMID- 4026272 TI - In vitro activity of cefbuperazone against Bacteroides spp. AB - The activity of cefbuperazone was tested in vitro against 287 clinical isolates of Bacteroides spp. Cefbuperazone showed good activity against B. fragilis, B. vulgatus, and other Bacteroides species, comparable to that of cefoxitin. It was relatively ineffective against B. distasonis and the B. thetaiotaomicron-ovatus group and was not active against cefoxitin-resistant Bacteroides spp. PMID- 4026273 TI - Self-induced nystatin resistance in Dictyostelium discoideum. AB - The cellular slime mold Dictyostelium discoideum is normally susceptible to the action of the polyene antibiotic nystatin. We describe conditions under which transient nystatin resistance can be induced in the absence of detectable changes in sterol composition. These results suggest that nystatin plays a positive role in promoting resistance to itself. PMID- 4026274 TI - Simultaneous determination of dacarbazine, its photolytic degradation product, 2 azahypoxanthine, and the metabolite 5-aminoimidazole-4-carboxamide in plasma and urine by high-pressure liquid chromatography. AB - A high-pressure liquid chromatographic method has been developed that allows for the simultaneous analysis of dacarbazine (DTIC), 5-aminoimidazole-4-carboxamide (AIC), and 2-azahypoxanthine (2-AZA) in plasma or urine. Plasma samples were prepared by ultrafiltration, whereas urine samples were filtered and diluted for analysis. Chromatography was done with a C18 mu Bondapak column along with gradient elution of the drugs. The mobile phase consisted of 100% 0.5 M sodium acetate (pH 7.0) and 25% acetonitrile in 0.05 M sodium acetate (pH 5.5) with detection at 280 nm. Linearity was observed up to 500 micrograms/ml for DTIC and up to 53 micrograms/ml for AIC and 2-AZA. The assay methodology was reproducible, with a lower limit of detection of 5.0, 0.5, and 0.5 micrograms/ml for DTIC, AIC, and 2-AZA, respectively. Interday and intraday coefficients of variation ranged between 4 to 14% and 2 to 16%, respectively. The analytical method was applied to the analysis of plasma and urine samples resulting from the isolation perfusion chemotherapy of an extremity with 57 mg of DTIC per kg in a patient with melanoma. PMID- 4026275 TI - In vitro comparative antimicrobial activity of cefpimizole against clinical isolates from five medical centers. AB - Cefpimizole was compared with cefoperazone and cefotaxime against 6,599 clinical bacterial isolates from five medical centers. Cefoperazone and cefotaxime were both more active and provided a greater spectrum of antimicrobial coverage than cefpimizole. Some of the cefpimizole minimum concentrations inhibiting 50% of tested strains were as follows: Citrobacter freundii and Enterobacter cloacae, 16 micrograms/ml; Escherichia coli and Klebsiella pneumoniae, 2.0 micrograms/ml; Proteus mirabilis, 1.0 microgram/ml; Pseudomonas aeruginosa, 16 micrograms/ml; Staphylococcus spp., 32 micrograms/ml; and the enterococci, greater than 32 micrograms/ml. PMID- 4026276 TI - An adjustment error in optimization of taste intensity. AB - In a currently popular method of adjustment for assessing optimal preferred levels of tastants in foods, a robust perceptual error was observed. When subjects concentrated a dilute beverage to optimal taste, the final (adjusted) concentration of the added tastant was reliably lower than when diluting a concentrated beverage. This discrepancy between ascending and descending runs was observed for both adjusted sucrose in a fruit beverage and for adjusted NaCl in tomato juice. The premature shift in perception from non-optimal to optimal judgment resembles the "error of anticipation" in the classical method of limits. The effect could not be attributed to sensory adaptation or perceptual insensitivity, and it persisted even when subjects were told to be sure to reach the same level in both directions of adjustment. The magnitude of the error was diminished by interweaving of ascending and descending trials, which altered the immediate stimulus context, and by enhancing the motivational level of subjects (through reward) to try to reach the same concentration in both ascending and descending adjustments. PMID- 4026277 TI - The relationship of attitudes and experiences of Finnish youths to their hedonic responses to sweetness in soft drinks. AB - Attitudes to sugar and previous experience (liking and use at present and in childhood) of sweet foods as well as hedonic responses to two levels of sweetness in soft drinks were determined in a young adult population (112 males, 112 females). Females were more negative in their attitudes but they reported greater liking of sweet foods. Sugar attitudes were not related to hedonic responses to normal sweetness (9%) in either sex group, but in the case of lower sweetness (5%) negative attitudes increased along with the rated pleasantness, particularly among males. Reported liking and use of soft drinks had some significant correlations with hedonic responses to both sweetness levels, but experiences of other sweet foods were not related to the hedonic responses to sweetness in soft drinks. PMID- 4026278 TI - Stimulus range influences intensity and hedonic ratings of flavour. AB - Five concentrations of an artificial orange drink were presented for sensory evaluation in three overlapping concentration ranges. Three sensory panels, each of 30 subjects, rated the concentrations for intensity of flavour (intensity scale), relation to ideal flavour intensity (ideal-point scale), and pleasantness (hedonic scale). Except for the two extreme concentrations, neither of which was presented in more than one range, in all three response tasks the mean rating for a given concentration varied with the concentration range in which it was presented. However, the mean ratings showed good correspondence across response tasks (e.g. the concentration perceived as "moderately sweet" on the intensity scale was perceived as "just right" on the ideal-point scale and of maximal pleasantness on the hedonic scale), suggesting a link between the intensity and hedonic dimensions of sensory experience. PMID- 4026279 TI - Different metabolites might reduce food intake by the mitochondrial generation of reducing equivalents. AB - To test the possibility that hypophagic effects of injected metabolites are linked to a particular oxidative step in their metabolism, cumulative food intake in rats after subcutaneous injection of various metabolites or their immediate oxidation products was investigated. Glycerol was compared with dihydroxyacetone, L-malate with oxaloacetate, and L-lactate with pyruvate. Subcutaneous injection of 4.5 mmol/kg metabolic body weight (BW0.75) of glycerol or malate reduced food intake significantly, whereas the same doses of dihydroxyacetone or oxaloacetate did not. Lactate or pyruvate (4.5 mmol/kg BW0.75, each) both reduced food intake significantly. However, even higher doses (7.7 mmol/kg BW0.75) of lactate or pyruvate failed to affect food intake when rats were fed a high fat (HF) diet, which is known to decrease the activity of the enzyme pyruvate dehydrogenase. In an additional experiment, subcutaneous injection of lactate or pyruvate (7.7 mmol/kg BW0.75, each) increased plasma levels of lactate and pyruvate 2 h after the injection in HF-rats more than in rats fed the usual high-carbohydrate diet. The data are consistent with the hypothesis that the increased generation of reducing equivalents in the mitochondria, brought about by the oxidation of injected glycerol, malate, lactate, or pyruvate, reduces food intake in rats. PMID- 4026280 TI - Histamine: a role in normal drinking. AB - Little is known about the physiological mechanisms that control normal drinking and, in particular, drinking around mealtime. This problem has recently been penetrated by experiments evaluating a role for histamine in drinking elicited by eating. This work supports the hypothesis of a preabsorptive, pregastric, vagally mediated, histaminergic component of drinking elicited by eating in the rat. PMID- 4026281 TI - Abstracts: The neural and metabolic bases of feeding. Napa Valley, California, 7 9 October, 1984. A satellite symposium of the 14th annual meeting of the Society for Neuroscience. PMID- 4026282 TI - Surface modification of proteins. Activation of monomethoxy-polyethylene glycols by phenylchloroformates and modification of ribonuclease and superoxide dismutase. AB - A single-step method of activation of monomethoxypolyethylene glycols suitable for its binding to polypeptides and proteins is proposed. Based on the reaction with 2,4,5-trichlorophenylchloroformate or p-nitrophenylchloroformate, it gives reactive PEG-phenylcarbonate derivatives. The PEG intermediate is stable on storage, the activating group is easily quantified,and the reaction with amino acid and proteins proceeds rapidly at pH near neutrality. The PEG derivatization of enzymes with this procedure is less inactivating than those previously reported. Ribonuclease and superoxide dismutase were modified and the effect of (a) bound polymer on clearance time in rats, (b) antibody recognition, and (c) on the enzymatic activity toward low and high molecular weight substrates were studied. PMID- 4026283 TI - Characterization and comparison of soluble and immobilized pig muscle aldolases. AB - Pig muscle aldolase was insolubilized by covalent attachment to a polyacrylamide matrix containing carboxylic functional groups. The catalytic activity of the Akrilex C-aldolase was 2014 units/g solid, i.e., an activity loss of only about 5% relative to the initial activity. The pH optimum for catalytic activity shifted form 7.25 to 7.5 and the apparent temperature optimum from 313 to 318 K. The Michaelis constant of the insolubilized enzyme was significantly higher than that of the soluble aldolase. Heat- and urea-inactivation experiments revealed that the immobilization increased the stability of the enzyme. PMID- 4026284 TI - Metabolism of the benzidine-based azo dye Direct Black 38 by human intestinal microbiota. AB - Benzidine-based azo dyes are proven mutagens and have been linked to bladder cancer. Previous studies have indicated that their initial reduction is the result of the azo reductase activity of the intestinal microbiota. Metabolism of the benzidine-based dye Direct Black 38 was examined by using a semicontinuous culture system that simulates the lumen of the human large intestine. The system was inoculated with freshly voided feces, and an active flora was maintained as evidenced by volatile fatty acid and gas production. Within 7 days after exposure to the dye, the following metabolites were isolated and identified by gas chromatography-mass spectrometry:benzidine, 4-aminobiphenyl, monoacetylbenzidine, and acetylaminobiphenyl. Benzidine reached its peak level after 24 h, accounting for 39.1% of the added dye. Its level began to decline, and by day 7 the predominant metabolite was acetylaminobiphenyl, which accounted for 51.1% of the parent compound. Formation of the deaminated and N-acetylated analogs of benzidine, which have enhanced mutagenicity and lipophilicity, previously has not been attributed to the intestinal microbiota. PMID- 4026285 TI - TDP-1, a toxic component causing tibial dyschondroplasia in broiler chickens, and trichothecenes from Fusarium roseum 'Graminearum'. AB - Fusarium roseum 'Graminearum' was isolated from overwintered oats in Alaska and was tested for its ability to cause tibial dyschondroplasia (TDP) in broiler chickens. The water-soluble fraction was tested and found to cause TDP. In addition, diacetoxyscirpenol and 7-hydroxydiacetoxyscirpenol were identified in the acetonitrile fraction of the extracts and caused mild mouth lesions in chickens. Six major water-soluble components were purified by thin-layer chromatography and tested for toxicity to chick embryos. One of the six components, called TDP-1, was found to be lethal to chick embryos. There was a 100% incidence of TDP in chickens fed a diet containing 75 ppm (wt/wt) of pure TDP-1, thus establishing the cause and effect relationship between TDP and TDP-1. Analyses by thin-layer chromatography and mass spectrometry revealed that TDP-1 is polar and ninhydrin positive, exhibits fluorescence with UV irradiation, and is a nitrogen-containing component with an empirical formula of C15H20N2O4. PMID- 4026286 TI - Modification of in vitro metabolism of T-2 toxin by esterase inhibitors. AB - In vitro metabolism of T-2 toxin with S-9 fraction obtained from livers of phenobarbital-treated pigs and rats in the presence of different esterase inhibitors, including NaF, p-hydroxymercuribenzoate, phenylmethylsulfonyl fluoride, eserine sulfate, diisopropylfluorophosphate, and diethyl p-nitrophenyl phosphate, was studied. The metabolism was completely shifted to the hydroxylation at the C-3' position in the T-2 toxin molecule when esterase inhibitors were present. Diethyl p-nitrophenyl phosphate was found to be the most potent among six esterase inhibitors tested. In the presence of 10(-4) M diethyl p-nitrophenyl phosphate, 3'-hydroxy-T-2 toxin was the only metabolite detected. Similar results were obtained when other T-2-related metabolites were tested. The yield of conversion of T-2 toxin, acetyl T-2 toxin, HT-2 toxin and T-2 triol to their respective 3'-hydroxyl derivatives were 82, 73, 72, and 75%, respectively. PMID- 4026287 TI - Enrichment medium for isolation of Campylobacter jejuni-Campylobacter coli. AB - A broth enrichment medium for the improvement of isolation of Campylobacter jejuni-Campylobacter coli from stool samples and other specimens is presented. Of 1,228 samples examined in parallel, positive results were obtained from 81 by direct inoculation of selective media and from 112 after enrichment. Thus, an increase of 27.7% in the isolation rate was obtained by using the enrichment medium. The same medium without antibiotics allows the preservation of isolates of C. jejuni-C. coli for at least 2 months at 4 degrees C. PMID- 4026288 TI - Response of the microflora in outdoor experimental streams to pentachlorophenol: compartmental contributions. AB - Outdoor artificial streams were treated continuously with pentachlorophenol (PCP) for 88 days during the summer of 1983. The contributions of different stream compartments (microbial habitats) to microbial degradation of PCP were determined in a stream treated with 144 micrograms of PCP per liter. The 488-m long stream was composed of mud-bottomed pools alternating with gravel riffles. PCP loss in the stream attributable to microbial degradation after an adaptation period was in the range of 55 to 74%. Contributions to PCP loss were determined for rock surface (epilithic), macrophyte surface (epiphytic), sedimentary, and water column communities by measuring rates of PCP disappearance in stream water, containing ambient concentrations of PCP, in contact with representative compartmental samples. The specific capability, in units of micrograms of PCP per hour per square meter of stream cross-sectional area (macrophytes at maximum plant density, water column at mean depth, upper 10-cm layer of gravel), followed the order rock surface much greater than macrophytes greater than sediment approximately equal to water column. The compartmental contribution to total stream losses in units of grams per hour followed the same order, although the differences were smaller. The rate of PCP disappearance in the water column above sediment cores followed the order oxygen-rich greater than oxygen-poor approximately equal to anaerobic greater than sorption-only conditions. The large difference in specific capability between the rock surface and sediment compartments could be attributed to oxygen deficiency (because of chemical and biological oxygen demand) in the sediments. Free-floating and particle-attached organisms in the water column were important to PCP biodegradation. PMID- 4026289 TI - Seasonal changes in the ruminal microflora of the high-arctic Svalbard reindeer (Rangifer tarandus platyrhynchus). AB - The dominant rumen bacteria in high-arctic Svalbard reindeer were characterized, their population densities were estimated, and ruminal pH was determined in summer, when food quality and availability are good, and in winter, when they are poor. In summer the total cultured viable population density was (2.09 +/- 1.26) X 10(10) cells ml-1, whereas in winter it was (0.36 +/- 0.29) X 10(10) cells ml 1, representing a decrease to 17% of the summer population density. On culture, Butyrivibrio fibrisolvens represented 22% of the bacterial population in summer and 30% in winter. Streptococcus bovis represented 17% of the bacterial population in summer but only 4% in winter. Methanogenic bacteria were present at 10(4) cells ml-1 in summer and 10(7) cells ml-1 in winter. In summer and winter, respectively, the proportions of the viable population showing the following activities were as follows: starch utilization, 68 and 63%; fiber digestion, 31 and 74%; cellulolysis, 15 and 35%; xylanolysis, 30 and 58%; proteolysis, 51 and 28%; ureolysis, 40 and 54%; and lactate utilization, 13 and 4%. The principal cellulolytic bacterium was B. fibrisolvens, which represented 66 and 52% of the cellulolytic population in summer and winter, respectively. The results indicate that the microflora of the rumen of Svalbard reindeer is highly effective in fiber digestion and nitrogen metabolism, allowing the animals to survive under the austere nutritional conditions typical of their high-arctic habitat. PMID- 4026290 TI - Nutritionally limited pectinolytic bacteria from the human intestine. AB - A selective procedure was used to isolate pectinolytic intestinal bacteria from human subjects. The three isolates with the greatest pectinolytic activity utilized pectin and a few related compounds as fermentable substrates for growth but did not utilize any other compound tested. Thus, their substrate utilization pattern was markedly different from that of previously described intestinal pectinolytic isolates. The three isolates are representatives of a nutritionally defined group of bacteria for which the term pectinophilic is proposed. PMID- 4026291 TI - Immunochemical study of triton X-100-soluble surface components of slime-forming, encapsulated Streptococcus cremoris from the fermented milk product viili. AB - Crossed immunoelectrophoresis was used to study Triton X-100-soluble cell components of Streptococcus cremoris T5 from viili. The antiserum was raised against whole cells, and the antigens extracted gave a complex precipitate pattern with 16 prominent and reproducible precipitates. The results of immunoadsorption experiments with whole cells suggest that six antigens are expressed on the cell surface, and the exposure of cell surface antigens is greater on cells from the early stationary growth phase than on those from the late exponential phase. PMID- 4026293 TI - Effects of diffusion on the electrophoretic behavior of associating systems: the Gilbert-Jenkins theory revisited. AB - The Gilbert-Jenkins theory predicts the asymptotic shape of moving-boundary sedimentation and electrophoretic patterns and broad zone molecular sieve chromatographic elution profiles for the class of interacting systems, A + B in equilibrium C, in which two dissimilar macromolecules react reversibly to form a complex. A particularly provocative case is the one in which the complex has a greater migration velocity than that of either reactant, each of which has a different velocity. Depending upon conditions, this case predicts, for example, that in the asymptotic limit an ascending electrophoretic pattern or a frontal gel chromatographic elution profile can show two hypersharp reaction boundaries separated by a plateau. This prediction is now confirmed by numerical solution of transport equations which retain the second-order diffusional term and extrapolation of the computed patterns to zero diffusion coefficient. For finite diffusion coefficient, however, the two hypersharp reaction boundaries are separated by a weak negative gradient. These calculations are extended to an examination of the transitions between the three types of patterns admitted by the case under consideration in order to gain physical understanding and to define criteria for recognizing the transitions. Studies of this kind not only establish confidence in the Gilbert-Jenkins theory, but, in addition, they provide new insights which make for more effective application of the theory to real systems. PMID- 4026292 TI - Intestinal microbial flora after feeding phytohemagglutinin lectins (Phaseolus vulgaris) to rats. AB - Incorporation of purified phytohemagglutinin (PHA) lectins derived from red kidney beans (Phaseolus vulgaris) in the diet of weanling rats will cause growth failure, malabsorption of nutrients, and bacterial overgrowth in the small intestine. These effects are not caused by feeding a similar quantity of PHA to germfree rats. To define the morphological and bacterial changes on the mucosal surfaces of the jejunum, ileum, and cecum in greater detail, we pair fed two groups of weanling rats isocaloric, isonitrogenous diets with or without 0.5% PHA protein. On the jejunal surfaces of control rats, the mucous layer was a confluent covering with sparsely scattered bacteria and protozoa. In PHA-treated rats, the mucous layer was thin and discontinuous, and the microvillous surface of the tissue was extensively populated by bacterial cells of two distinct morphotypes--a gram-negative rod and a gram-positive coccobacillus. In all PHA treated animals, these bacteria formed adherent monospecific or mixed adherent microcolonies on the tissue surface. Tissue damage was observed in PHA-exposed jejunal tissue as evidenced by vesiculation of the microvillous plasma membrane and by damage to the brush border membrane. On the ileal surfaces of control rats, there was a thick mucous layer within which small numbers of bacteria and protozoa were seen. Segmented filamentous bacteria were anchored in the tissue surface. In PHA-treated rats, the ileal surface was only incompletely covered by a mucous layer, and the overlying mucosal surface was extensively covered by large numbers of protozoan cells (predominantly Hexamita muris). Most of the ileal surfaces not covered by the mucous layer were occupied and virtually occluded by an overgrowth of these protozoan cells with occasional cells of Giardia muris and the tissue-associated segmented bacillus. In the ceca of control rats, the mucosa was incompletely covered by a discontinuous mucous layer and colonized by an unnamed Spirillum sp., other bacteria, and occasional protozoa. The cecal surfaces of PHA-treated rats retained most of their incomplete overlying mucous layer, which was heavily colonized by the same type of Spirillum sp. seen in untreated animals; intestinal crypts were colonized. These descriptive morphological studies demonstrate that exposure to purified PHA in the diet caused characteristic changes in the microbial ecology of the small intestine. The changes in microbial flora contributed to the malabsorption of nutrients in the small intestines of PHA-fed animals. PMID- 4026295 TI - Distribution of oxidized and reduced forms of glutathione and cysteine in rat plasma. AB - The distribution of the glutathionyl moiety between reduced and oxidized forms in rat plasma was markedly different than that for the cysteinyl moiety. Most of the glutathionyl moiety was present as mixed disulfides with cysteine and protein whereas most of the cysteinyl moiety was present as cystine. Seventy percent of total glutathione equivalents was bound to proteins in disulfide linkage. The distribution of glutathione equivalents in the acid-soluble fraction was 28.0% as glutathione, 9.5% as glutathione disulfide, and 62.6% as the mixed disulfide with the cysteinyl moiety. In contrast, 23% of total cysteine equivalents was protein bound. The distribution of cysteine equivalents in the acid-soluble fraction was 5.9% as cysteine, 83.1% as cystine, and 10.8% as the mixed disulfide with the glutathionyl moiety. A first-order decline in glutathione occurred upon in vitro incubation of plasma and was due to increased formation of mixed disulfides of glutathione with cysteine and protein. This indicates that plasma thiols and disulfides are not at equilibrium, but are in a steady-state maintained in part by transport of these compounds between tissues during the inter-organ phase of their metabolism. The large amounts of protein-bound glutathione and cysteine provide substantial buffering which must be considered in analysis of transient changes in glutathione and cysteine. In addition, this buffering may protect against transient thiol-disulfide redox changes which could affect the structure and activity of plasma and plasma membrane proteins. PMID- 4026294 TI - Inhibition of carnitine acetyltransferase by metabolites of 4-pentenoic acid. AB - The inhibition of carnitine acetyltransferase (EC 2.3.1.7) by metabolites of 4 pentenoic acid was studied. 3-Keto-4-pentenoyl-CoA, a beta-oxidation metabolite of 4-pentenoic acid, was found to be an effective inhibitor of the enzyme in the presence, but not in the absence of L-carnitine. Since acetyl-CoA protects the enzyme against this inhibition, 3-keto-4-pentenoyl-CoA seems to be an active site directed inhibitor. 3-Keto-4-pentenoyl-CoA, which is a substrate of carnitine acetyltransferase, causes the irreversible inactivation of the enzyme. All observations together lead to the suggestion that 3-keto-4-pentenoyl-CoA is a mechanism-based inhibitor of carnitine acetyltransferase. PMID- 4026296 TI - Effect of divalent cations on the limited proteolysis of prothrombin by thrombin. AB - The inhibitory influence of divalent cations on the ability of bovine alpha thrombin to hydrolyze prothrombin showed the trend Mn2+ much greater than Ca2+ greater than or equal to Mg2+ greater than Sr2+ much greater than Ba2+. This effect was not due to an inhibition of thrombin's catalytic activity as measured by hydrolysis of a specific synthetic substrate, H-D-Phe-pipecolyl-Arg-p nitroanilide (D-PhePipArgNA). The presence of divalent cations did not inhibit thrombic proteolysis of gamma-carboxyglutamic acid (Gla)-domainless prothrombin. Prothrombin and Gla-domainless prothrombin were used as competitive inhibitors in the thrombic hydrolysis of D-PhePipArgNA. The apparent Ki value calculated for prothrombin was 18 microM. When either Ca2+ or Mn2+ were present, there was no inhibition. The apparent Ki value determined for Gla-domainless prothrombin was 28 microM in either the absence or presence of Ca2+. Addition of divalent cations to prothrombin, but not to Gla-domainless prothrombin, resulted in an altered protein conformation as measured by high-performance size-exclusion chromatography and ultraviolet difference spectroscopy. These results suggest that a conformational change secondary to the interaction of divalent cations with the Gla-containing domain of prothrombin is required for cation-dependent inhibition of thrombin hydrolysis. PMID- 4026297 TI - Glutathione changes occurring after S-adenosylhomocysteine hydrolase inhibition. AB - Freshly isolated rat hepatocytes, which metabolize methionine through the cystathionine pathway, and cultured L5178Y cells, which do not, were compared for their response to the inhibition of S-adenosylhomocysteine (SAH) hydrolase (EC 3.3.1.1). When cells were incubated in Fischer's medium lacking cystine but containing 0.67 mM methionine and 10% serum, the addition of periodate-oxidized adenosine (POA), an inhibitor of SAH hydrolase, increased the level of SAH approximately 4-fold in L5178Y cells (5 mM POA) and 30-fold in hepatocytes (1 mM POA). POA treatment also decreased the amount of intracellular glutathione (GSH) in hepatocytes by 6-fold, and in L5178Y cells by 3-fold. Incubation of hepatocytes with adenosine plus homocysteine, 2-chloroadenosine, or 2',3'-acyclic adenosine increased intracellular SAH and also lowered GSH levels. Neither GSH oxidation nor efflux of GSH or GSH conjugates appeared to account for the GSH loss. Intracellular GSH, covalently bound to proteins as mixed disulfides, increased when hepatocytes were incubated with POA, but the increase was insufficient to account for the total GSH loss. In hepatocytes with prelabeled [35S]GSH, POA caused the cellular GSH content to decrease while the specific activity of [35S]GSH remained constant, suggesting that inhibitor treatments that caused elevated SAH levels may have increased the degradation of GSH while GSH synthesis was inhibited. PMID- 4026298 TI - The conformation of the C-terminal region of actin: a site-specific photocrosslinking study using benzophenone-4-maleimide. AB - The site-specific photocrosslinker, benzophenone-4-maleimide, was used to label G actin specifically at Cys-374, the penultimate residue from the C terminus. The resultant BP-G-actin was polymerized to form BP-F-actin, and both forms of actin were irradiated to activate the benzophenone moiety. We found that for BP-F-actin both intersubunit and intrasubunit photocrosslinks were formed. For BP-G-actin only a small amount of an internally photocrosslinked species was formed. These findings suggest that in the F-actin polymer, the C-terminal peptide is localized in a region between neighboring subunits. In contrast, in the G-actin monomer, the C-terminal peptide is relatively distant from the surface of the molecule. PMID- 4026299 TI - Regulation of phosphoenolpyruvate carboxylase from Crassula by interconversion of oligomeric forms. AB - Using size-exclusion high-performance liquid chromatography, it is shown that phosphoenolpyruvate carboxylase from Crassula argentea, a crassulacean acid metabolism (CAM) plant, exists primarily in the form of a tetramer of a 100-kDa subunit at night and as a dimer of the same subunit during the day. The tetrameric enzyme from night leaves is not inhibited by malate, while the dimeric form from day leaves can be completely inhibited by malate. The purified day, or dimer, form of the enzyme can be converted to the tetramer by concentration and exposure to Mg2+. When thus converted, the tetramer is insensitive to malate inhibition, and is more strongly activated by glucose 6-phosphate than the dimer. The purified night, or tetramer, form is converted to the dimer by incubation for 60 min at pH 8.2. This enzyme may also be converted to the dimer by adding 1.5 mM malate to the elution buffer, but preincubation for 15 min with phosphoenolpyruvate prevents disaggregation when chromatographed with buffer containing malate. Preincubation with 1mM EDTA and subsequent chromatography with buffer containing malate shows a progressive dissociation of the tetrameric form with increasing time of preincubation. The implications of these observations for the diurnal regulation of phosphoenolpyruvate carboxylase in CAM metabolism are discussed. PMID- 4026300 TI - Relationships between the rate of synthesis of ATP and the concentrations of reactants and products of ATP hydrolysis in maize root tips, determined by 31P nuclear magnetic resonance. AB - Using 31P NMR spectroscopy, we have measured the rate of ATP synthesis, and the free concentrations of ATP, ADP, cytoplasmic Pi, and H+ in maize root tips under a wide range of conditions. We show that the ratio [ATP]/[ADP] in normoxic root tips is greater than 25. We found no simple relationship between the concentration of ATP and the rate of ATP synthesis: when the rate of ATP synthesis decreases in response to different treatments, the concentration of ATP can increase, decrease, or remain unchanged. Clear relationships were obtained, however, when the rate of synthesis of ATP was plotted against the logarithm of the ratio psi, defined as [ATP]/[ADP][Pi][H+]. Two curves were obtained, depending on which of two situations pertained. First, if mitochondrial ATP synthesis was inhibited, e.g., by KCN or hypoxia, ln psi decreased monotonically as rates of ATP synthesis decreased. The decrease in ln psi may account for decreases in the rates of biosynthetic reactions dependent on ATP, such as protein synthesis, as they approach equilibrium. Second, if consumption of ATP for biosynthetic reactions was inhibited, by treatment with succinate, ln psi increased as rates of ATP synthesis decreased. The increase in ln psi may account for decreases in the rate of ATP synthesis, as oxidative phosphorylation approaches equilibrium. PMID- 4026301 TI - Determination of anesthetic molecule environments by infrared spectroscopy. I. Effects of solvating molecule structure on nitrous oxide spectra. AB - The effects of the medium on the infrared spectrum of nitrous oxide (N2O) were determined in the antisymmetric stretch region near 2200 cm-1 for solutions of N2O in 38 different solvents at 25 degrees C. The solvents were chosen to reflect the variety of environments potentially available in sites occupied by N2O in nerve and other tissue. Band parameters of overlapping fundamental and hot bands were obtained with deconvolution techniques. Differences in solvent molecule structure had marked effects on both the frequency and the shape of the infrared bands. The fundamental band frequency (v3) ranged from 2215 cm-1 for carbon disulfide to 2230 cm-1 for water. Among the alcohols, v3 increased nearly linearly with increasing dielectric constant. However, solvent parameters that reflect bulk properties of the solvent did not correlate well with v3 over the entire range of solvents studied. Rather short-range specific solute-solvent molecular interactions appear particularly important. In general, v3 increases with the strength and number of dipoles in adjacent solvent molecules interacting with the vibrating dipole of N2O. Half-bandwidths (delta v1/2) ranged from 7.4 cm 1 for carbon tetrachloride to 14.4 cm-1 for hexane. Variations in bandwidth did not correlate in any direct way with solvent polarity, but delta v1/2 did increase with an increase in the conformational flexibility of the solvent molecule, which results in a greater diversity in the immediate environment about the N2O molecules. The observed sensitivity of the N2O infrared band parameters to changes in solvation environment and the appearance of the antisymmetric stretch band at a frequency within a window of relatively low-energy absorption by water makes infrared spectroscopy potentially useful for the characterization of the sites occupied by the anesthetic molecules within lipid, protein, and aqueous components of intact tissue. PMID- 4026302 TI - Determination of anesthetic molecule environments by infrared spectroscopy. II. Multiple sites for nitrous oxide in proteins, lipids, and brain tissue. AB - The presence of molecules of the general anesthetic nitrous oxide (N2O) in oils, esters, proteins, red cells, cream, lipid vesicles, and brain tissue upon exposure to the gas was observed by infrared spectroscopy. Analysis of the N-N-O antisymmetric stretch band reveals a distribution of N2O molecules among several sites of differing polarity in these solutions and tissues. The sensitivity of the band intensity and frequency to the number and strength of the dipoles in the solvating molecules is demonstrated by the resolution of N2O-ester and N2O-alkane interactions in acetic acid ethyl ester and oleic acid methyl ester. In all aqueous solutions and in all tissues a population of N2O molecules in water is observed. At least two sites of N2O-protein interaction are observed in purified hemoglobin A and packed red cells; multiple N2O sites may also be present in bovine serum albumin. Two sites of N2O-lipid interaction are observed in whipping cream and in an aqueous suspension of phosphatidylcholine vesicles. The sites providing the least polar immediate environment to N2O in hemoglobin, cream, and vesicles give similar band frequencies to those found in pure alkane solvents. Infrared spectra of bovine brain tissue, upon exposure to N2O, show N2O molecules present in water and in two less-polar environments. Analysis of spectra of N2O in cerebellum tissue removed from a dog under halothane-N2O anesthesia reveals, in addition to N2O in water, a single population of N2O molecules in an alkane like environment. Infrared spectroscopy provides a unique means of probing the structure of the environment of N2O and should prove useful in correlating anesthetic potency with anesthetic environment under physiological conditions. PMID- 4026304 TI - Structural characterization of the calcium binding protein s100 from adipose tissue. AB - A partial amino acid sequence for bovine adipose tissue S100 was elucidated by characterization of peptides generated by cyanogen bromide cleavage. The cyanogen bromide peptides were aligned by homology with the bovine brain S100 beta sequence. The results demonstrate that adipose S100 beta is probably identical to brain S100 beta, and suggest that S100 beta is a conserved protein among tissues of the same species. PMID- 4026303 TI - Metabolism of [3H]leupeptin by rat liver. AB - Tritium-labeled leupeptin was used to study how this tripeptide proteinase inhibitor interacts with the liver, including the mechanism of its transport into the cell, its subcellular distribution after uptake, and its metabolism once in the tissue. Experiments were done in situ and in a perfused liver. At low concentrations (1 to 10 microM) the uptake of radioactive inhibitor was competed by chemically reduced leupeptin. At high concentrations at least up to 400 microM the uptake was directly proportional to the external concentration of tripeptide. Entry into the tissue essentially stopped at low temperature (less than 21 degrees C). [3H]Leupeptin initially was located in the soluble fraction of the liver homogenate and by 15 to 30 min became concentrated in the lysosome-rich fraction. During 2 h of perfusion almost 50% of [3H]leupeptin that had entered the liver was secreted intact into the bile. In addition, a portion of the leupeptin that remained in the liver was degraded during this time period. PMID- 4026305 TI - The effect of pyridoxine deficiency on the metabolism of the aromatic amino acids by isolated rat liver cells. AB - The total activity of three key enzymes and the flux through eight steps of aromatic amino acid metabolism have been determined in liver cells isolated from rats fed either control or pyridoxine-free diet for 5-6 weeks. The pyridoxine free diet caused a decrease in the catabolism of tyrosine and phenylalanine because of a drop in the flux through tyrosine aminotransferase. This decrease of expressed cellular tyrosine aminotransferase activity can be fully explained in terms of loss of cofactor. Larger decreases in the catabolism of tryptophan were seen after pyridoxine deprivation. The decreased extent of tryptophan catabolism can be solely attributed to loss of cofactor or increased degradation of kynureninase. Inhibition of tryptophan 2,3-dioxygenase was seen in pyridoxine deficiency, probably because of the buildup of the kynurenine metabolites. The control strength of kynureninase, for flux through kynureninase, was calculated to be less than or equal to 0.004, but 0.41 after pyridoxine deprivation. The sensitivity of the three pathways to pyridoxine deprivation is interpreted and discussed in terms of the different affinities for pyridoxal phosphate and the control strengths of the pyridoxal phosphate-dependent enzymes, tyrosine aminotransferase and kynureninase. PMID- 4026306 TI - Specificity of two different purified acylcarnitine hydrolases from rat liver, their identity with other carboxylesterases, and their possible function. AB - One of the previously described five purified monoglyceride-cleaving carboxylesterases from rat liver microsomes proved to be a carnitine ester hydrolase. This esterase, with an isoelectric point of 5.2, is most active with medium-chain acyl-L-carnitines (C12-C14). The esterase is also remarkably active with 1,3-diglycerides, especially 1,3-dioctanoylglycerol, that are hydrolyzed faster than the corresponding 1-monoglycerides and triglycerides. Only one of the other four purified carboxylesterases has moderate acylcarnitine-hydrolyzing activity. An altered procedure for the separation of the two microsomal acylcarnitine-cleaving enzymes is described. Both enzymes hydrolyze carnitine esters optimally at pH 8 and both are inactive with acetylcarnitine, palmitoyl CoA, and butyrylthiocholine. The possible natural functions of the hydrolases are discussed. Besides their detoxifying action on natural membrane-lysing detergents (like carnitine esters and lysophospholipids), these enzymes could be involved in the transport of carnitine out of the liver. PMID- 4026307 TI - Effect of pH on oligomeric equilibrium and saccharide-binding properties of peanut agglutinin. AB - The conformation and saccharide-binding properties of peanut agglutinin (PNA) depend on pH as studied by analytical ultracentrifugation, fluorescence, circular dichroism, equilibrium dialysis, and absorption spectroscopy. PNA is tetrameric in neutral solution and dissociates reversibly into dimers below pH 5.1. Below pH 3.4, the lectin is totally dimeric. Lowering of the pH induces reversible changes in the tertiary and secondary structures of PNA. Binding of saturating amounts of lactose to tetrameric (pH 6.9) or dimeric (pH 3.2) PNA resulted in identical ultraviolet difference spectra. Fluorescence studies of PNA as a function of pH in the presence of lactose indicated that tryptophanyl residues, present at or near the saccharide binding site, are more accessible to the ligand in dimeric than in tetrameric PNA. For solutions of dimeric PNA, containing only minor amounts of tetramers (pH 3.6), equilibrium dialysis with MeUmb-beta Gal beta(1--- 3)GalNac showed that the binding capacity of PNA was the same as for tetrameric PNA (one binding site per protomer) but the apparent association constant was one order of magnitude lower than for tetrameric PNA. The enhancement of MeUmb-beta Gal beta(1----3)GalNac fluorescence upon binding to PNA was pH dependent: 50% at neutrality, 16% at pH 3.7, and unobservable at pH 3.0, suggesting that the microenvironment of this PNA-bound chromophore changed progressively with pH and was dependent on ionization of an acidic amino acid residue. PMID- 4026308 TI - Biosynthesis of sulfoquinovosyldiacylglycerol in higher plants: the origin of the diacylglycerol moiety. AB - The positional distribution of fatty acids in chloroplast polar lipids and phosphatidylcholine from leaves of four plants has been measured in order to determine the origin of the diacylglycerol (DAG) moieties of each lipid. In spinach and tobacco, the DAG of sulfoquinovosyldiacylglycerol (SQDG), monogalactosyldiacylglycerol (MGDG) and digalactosylglycerol (DGDG) were derived partly from the chloroplast and partly from the cytoplasm. The contribution of the chloroplast pathway differed for each lipid, but in both plants the proportion of a lipid derived from that pathway was in the order SQDG greater than MGDG greater than DGDG. In contrast, all the DAG moieties of the three glycolipids of wheat and cucumber were derived from the cytoplasm. The DAG moiety of chloroplast phosphatidylglycerol was synthesized in the chloroplast in all four plants. PMID- 4026309 TI - Biosynthesis of sulfoquinovosyldiacylglycerol in higher plants: the incorporation of 35SO4 by intact chloroplasts. AB - Isolated spinach chloroplasts have been found to incorporate 35SO4 into the plant sulfolipid, sulfoquinovosyldiacylglycerol, at rates of up to 700 pmol mg chlorophyll-1 h-1. The reaction is light-dependent, requires that the chloroplasts be intact, and is slightly stimulated by ATP and UTP. UDP-galactose inhibits the formation of sulfoquinovosyldiacylglycerol, presumably by competing for the diacylglycerol pool. The rates of synthesis observed are sufficient to conclude that the chloroplast is autonomous with respect to the synthesis of sulfoquinovose, the headgroup moiety of sulfoquinovosyldiacylglycerol. No evidence could be obtained to support the concept that the proposed sulfoglycolytic pathway is the biosynthetic route for sulfoquinovose formation. PMID- 4026310 TI - Oligosaccharide chains of herpes simplex virus type 2 glycoprotein gG.2. AB - gG.2 glycoprotein was purified by H966 monoclonal antibodies linked to Sepharose from herpes simplex virus type 2-infected HEp-2 cells labeled with [3H] glucosamine. The glycoprotein was subjected to Pronase digestion and the glycopeptides were fractionated by Con A-Sepharose in a major fraction (88.5% of total radioactivity) unbound to the lectin gel and in a minor species which bound to the lectin as a N-linked diantennary oligosaccharide. Mild and strong acid hydrolysis of Con A-unbound and Con A-bound fractions revealed that (i) both species were highly sialylated; (ii) the Con A-unbound fraction contained mainly labeled N-acetylgalactosamine, as is the case for O-linked oligosaccharides; and (iii) the Con A-bound fraction carried the vast majority of the labeled N acetylglucosamine present in gG.2. Three size classes of oligosaccharides were separated from mild alkaline borohydride-treated Con A-unbound glycopeptides, which accounted for about 80% of the radioactivity present in the fraction. Galactosaminitol was recovered as the major labeled product in the strong acid hydrolyzates of the oligosaccharides generated by reductive beta-elimination, indicating that they were O-glycosidically linked to the peptide backbone. Thin layer and DEAE-Sephacel chromatography of the three O-linked oligosaccharide species indicated that disialylated tetrasaccharides and monosialylated trisaccharides were the major components, whereas neutral disaccharide was a minor component. Digestion with neuraminidase and beta-galactosidase of the O linked oligosaccharides supported the idea that the common disaccharide core was mainly of the structure beta-galactosyl-N-acetylgalactosamine. The large occurrence of O-linked oligosaccharides differentiates this type 2-specific herpes simplex virus glycoprotein from the type-common herpesvirus glycoproteins gB, gC, and gD. PMID- 4026311 TI - Alterations in motility and metabolism associated with sperm interaction with accessory sex gland fluids. AB - Sperm passing through the male tract interact with accessory sex gland fluids during ejaculation. Cellular metabolism is stimulated by this interaction for unknown reasons. These experiments involved calorimetric measurements [P.B. Inskeep and R.H. Hammerstedt (1983) J. Biochem. Biophys. Methods 7, 199-210] on ejaculated sperm (EJS) and cauda epididymal sperm (CES) from bulls to establish the contribution of individual pathways to total cellular ATP synthesis. Parallel incubations outside the calorimeter yielded samples for oxygen consumption measurements and for motility analysis, the major ATP-consuming reaction of sperm. Energy charge values were identical for incubations of EJS and CES with glucose, thereby establishing that the ratios of rates of ATP synthesis and degradation were equivalent for these cells under this incubation condition. The total rate of ATP synthesis was greater for EJS than for CES (5 vs 13 mumol ATP h 1/10(8) cells) with less than 2 mumol ATP h-1 for each cell type coming from degradation of endogenous reserves. Thus, ejaculation is associated with a large increase in catabolic rate that is satisfied by degradation of extracellular glucose. No difference in percentage of motile sperm was noted, but mean velocity was lower for CES (58 micron s-1) than for EJS (85 micron s-1). A difference in forward motility pattern was observed (wig-wag to flipping). We conclude from these data that interaction with accessory sex gland fluids alters ATP requiring activities of sperm, with one obvious alteration being their motility pattern. The increase in ATP requirement is satisfied by increased degradation of extracellular substrates, but not intracellular reserves, to provide sufficient ATP to satisfy cellular needs. PMID- 4026312 TI - A semisynthetic bovine pancreatic ribonuclease containing a unique nitrotyrosine residue. AB - A fully active semisynthetic ribonuclease, RNase 1-118:111-124, may be prepared by enzymatically removing six residues from the COOH terminus of the protein (positions 119-124) and then complementing the inactive RNase 1-118 with a chemically synthesized peptide containing the COOH-terminal 14 residues of the molecule (RNase 111-124) [M. C. Lin, B. Gutte, S. Moore, and R. B. Merrifield (1970) J. Biol. Chem. 245, 5169-5170]. Nitration of tyrosine-115 in the peptide followed by complex formation with RNase 1-118 affords a fully active enzyme containing a unique nitrotyrosine residue in a position which is known and which is very likely to be completely exterior to the active site region. The binding constant between the tetradecapeptide and RNase 1-118 (5 X 10(6) M-1 at pH 6.0) is not changed by the nitration. Crystals of the nitrated complex are isomorphous with those of RNase 1-118:111-124, for which a refined 1.8-A structure has recently been obtained. PMID- 4026313 TI - Molecular parameters and conformation of globoside and asialo-GM1. AB - Comparative studies of the individual properties and intermolecular organization of asialo-GM1 (Gg4Cer) and globoside (Gb4Cer) were made employing lipid monolayers and high-sensitivity differential scanning calorimetry. The surface pressure-area isotherm of Gb4Cer is more expanded than that of Gg4Cer. This results in greater molecular areas and compressibilities, and lower intermolecular interaction energies, for Gb4Cer compared to Gg4Cer at all surface pressures. This looser intermolecular packing may be responsible for a lower transition temperature (40.5 degrees C) and enthalpy of transition (delta Hcal) (2.0 kcal mol-1) found for the phase transition of Gb4Cer compared to Gg4Cer (54.0 degrees C and 4.2 kcal mol-1). The surface potential per molecule and resultant molecular dipole moment vector values are greater for Gb4Cer than for Gg4Cer at comparable values of surface pressure and molecular area. All these results reflect the existence of a rigid L-shape in the oligosaccharide chain of Gb4Cer that prevents a close intermolecular packing compared to the straight orientation of the polar head group of Gg4Cer. Significant movements of the oligosaccharide chain may occur depending on the lateral surface pressure. At low surface pressures the orientation of the oligosaccharide chain of Gg4Cer may be displaced an angle of up to about 40 degrees compared to the perpendicular position adopted at high surface pressures. In agreement with an enhanced liquid character of the interface, the oligosaccharide chain of Gb4Cer exhibits a greater freedom of movement and the displacement from the position perpendicular to the interface can reach to about 65 degrees. PMID- 4026314 TI - Properties of liver microsomal cholesterol 5,6-oxide hydrolase. AB - Cholestane 3 beta,5 alpha, 6 beta-triol has been identified as the exclusive product formed on hydration of cholesterol 5,6 alpha- and 5,6 beta-oxide catalyzed by cholesterol oxide hydrolase in liver microsomes obtained from five mammalian species. Highest activities were present in microsomes from rats and humans. Both acid- and base-catalyzed hydrolysis of the two epoxides also produce this product, presumably due to preference for pseudo-axial opening of the oxirane ring to form product with a trans-AB ring junction. Although the beta oxide is more reactive than the alpha-oxide upon acid-catalyzed hydration, the alpha-oxide is a 4.5-fold better substrate than the beta-oxide as indicated by values of Vmax/Km. The kinetic parameters Vmax and Km for the reaction catalyzed by rat liver microsomes are 1.68 +/- 0.15 X 10(-7) M min-1 and 10.6 +/- 1.5 microM for the alpha-oxide and 1.32 +/- 0.11 X 10(-7) M min-1 and 37.2 +/- 5.5 microM for the beta-oxide at 0.35 mg protein/ml, pH 7.4, 6.35% (v/v) CH3CN, and 37 degrees C. Several imino compounds are competitive inhibitors for the enzyme from rat liver. The most effective of these is 5,6 alpha-iminocholestanol (Ki = 0.085 microM) which was known to be a good inhibitor from previous studies. Inhibition by aziridines is consistent with the participation of acid catalysis in the mechanism of action of the enzyme. Cholesterol oxide hydrolase is a distinct enzyme from oxidosqualene cyclase as well as microsomal epoxide hydrolase (EC 3.3.2.3) and the recently reported mouse hepatic microsomal epoxide hydrolase that catalyzes the hydration of trans-stilbene oxide. PMID- 4026315 TI - Applicability of Henry's law to hydrogen, helium, and nitrogen solubilities in water and olive oil at 37 degrees C and pressures up to 300 atmospheres. AB - The solubilities of pure hydrogen, helium, and nitrogen in water and olive oil were measured at 37 degrees C at gas-saturation pressures from 25 to 300 atmospheres. Rigorous thermodynamic criteria were used to assess the applicability of Henry's law to the pressure dependence of the gas solubility in each system. The solubilities of the three gases in water and helium in olive oil followed Henry's law as given by the Krichevsky-Kasarnovsky equation. In contrast, hydrogen and nitrogen in olive oil each attained concentrations high enough to cause significant concentration-dependent variations of the dissolved gas activity coefficient and/or partial molal volume. The consequent deviations from Henry's law were greatest in the nitrogen-oil system, where mole fraction nitrogen solubilities calculated from the Krichevsky-Kasarnovsky equation exceeded measured values by 8, 14, and 23% at 50, 100, and 250 atm, respectively. Incorporation of results into the critical volume model of nitrogen anesthesia, using olive oil as a model of the physiological anesthetic site and literature data for the anesthetic potency of nitrogen in mice breathing high-pressure He-N2 O2 atmospheres, shows that nonideal solution behavior may become important for gases dissolved in physiological hydrophobic regions at biologically active concentrations, even if dissolved gas binding to proteins or other macromolecules is not involved. PMID- 4026316 TI - Proximate sulfhydryl groups in the acetylglutamate complex of rat carbamylphosphate synthetase I: their reaction with the affinity reagent 5'-p fluorosulfonylbenzoyladenosine. AB - A preparation of rat carbamylphosphate synthetase I, isolated in the presence of antipain and stable without glycerol, has been used to investigate the effect of the allosteric activator, N-acetyl-L-glutamate (AcGlu), on the sulfhydryl chemistry of the enzyme. The enzyme X AcGlu complex was rapidly inactivated by several sulfhydryl group reagents and the ATP analog, 5'-p fluorosulfonylbenzoyladenosine (FSO2BzAdo), with the loss of two sulfhydryl groups per monomer. Inactivation was much slower without AcGlu, and ATP/Mg2+/K+ provided complete protection. Reaction with a 1.1 molar excess of 4,4' dipyridyldisulfide resulted in an intramonomer disulfide bond between groups that are probably juxtaposed in the activated enzyme, because 1.1 equivalents of the vicinal dithiol reagent, phenylarsine oxide, eliminated the rapid reaction with the disulfide. Evidence is presented that the same disulfide bond was formed in the reactions with 5-thiocyano-2-nitrobenzoic acid and FSO2BzAdo. Inactivation by FSO2BzAdo was a pseudo-first-order reaction. The concentration dependence of the rate is consistent with the reaction proceeding through a noncovalent complex (KI = 67 microM and k2 = 0.23 min-1 at pH 7.0, 30 degrees C). Protection from FSO2BzAdo by ATP required Mg2+ in excess of ATP with KMgATP = 4.5 microM at saturating free Mg2+ (0.1 M K+) and KMg2+ = 6.5 mM. KMgATP is close to Kd for the molecule of ATP that contributes the phosphoryl group of carbamylphosphate (H.B. Britton, V. Rubio, and S. Grisolia, (1979) Eur. J. Biochem. 102, 521-530]; KMg2+ agrees with the minimum value for the steady-state kinetic parameter, Ki,Mg2+, obtained under the same conditions. Dissociation constants for adenosine (320 microM), MgADP (110 microM) at 10 mM Mg2+, and AcGlu (100 microM) were also estimated. PMID- 4026317 TI - The stability and transitions of tryptic-digested clathrin. AB - The pH-dependence of dissociation of trypsin-digested baskets has been determined by light scattering and compared with that of undigested baskets. Essentially no difference was found between the two types of baskets. The molecular transitions of clathrin derived from digested baskets have been studied by fluorescence spectra and polarization measurements and compared with those of undigested baskets. The transitions in both forms of clathrin were very similar. It is clear, therefore, that removal of about 1/3 of the mass from the distal portions of the arms of the clathrin triskelion does not affect its structural transitions. The interactions between clathrin molecules in the basket structure and those within the molecule appear, therefore, to remain intact in the smaller clathrin chains remaining after tryptic digestion. The function of the distal portion of the clathrin chain still awaits elucidation. PMID- 4026318 TI - Ultracentrifugation of concentrated biopolymer solutions and effect of ascorbate. AB - Highly concentrated solutions of bovine methemoglobin, human transferrin, proteoglycan-protein complex from bovine cartilage, and human hyaluronate were run to equilibrium in the preparative ultracentrifuge. The mass fraction, wo, of water in the compact part of the sediment ("the pellet") was studied as a function of the centrifugal force, ionic strength and pH. For the proteins, wo was close to 0.4 and varied only slightly on variation of the ionic strength and the force. For the proteoglycan-protein complex, wo was close to unity at low force but decreased sharply with increasing force, a finding which agrees well with the specific physical properties of the cartilage matrix. For hyaluronate, wo exceeded 0.8 even at the highest forces, but decreased sharply with increasing ionic strength. There appeared to be a relationship between wo and the carbohydrate mass fraction, wc, of the dry polymer material, wo increasing linearly with wc at 440,000g. A series of biologically or pharmacologically interesting substances was tested for a possible effect on wo of hyaluronate, and it was found that the addition of ascorbate (0.2 g/liter) caused a reduction of 0.040 in wo, independent of the force at which this parameter was measured. Simultaneously, the sedimentation coefficient was doubled. These findings suggest that, on reacting with ascorbate, the hyaluronate molecule changes from a random coil to a more compact molecule. PMID- 4026319 TI - Purification and properties of cytochrome P-450 from homogenates of human fetal livers. AB - A form of cytochrome P-450, namely P-450HFLa of human fetal livers, was purified to a specific content of 12.6 nmol/mg protein. The cytochrome P-450 preparation was electrophoretically homogeneous and had an apparent monomeric molecular weight of 51,000 as judged by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The cytochrome showed catalytic activities as oxidations of N methylaniline, ethylmorphine, N,N-dimethylaniline, N,N-dimethylnitrosamine, benzphetamine, aminopyrine, aniline, p-nitroanisole, and 7-ethoxycoumarin to various extents. In fetal liver homogenate, the amount of cytochrome P-450 that reacted with the antiserum to P-450HFLa accounted for more than 36% of the total cytochrome P-450 in three different fetal livers. On the other hand, the amount of P-450HFLa was less than 5% of the total cytochrome P-450 in adult liver microsomes. PMID- 4026320 TI - Secretion of a nonspecific lipid transfer protein by hepatoma cells in culture. AB - Nonspecific lipid transfer protein (sterol carrier protein2) has previously been proposed to function as (i) a catalyst for intracellular movement of newly synthesized phospholipid, (ii) a cofactor in the biosynthesis and metabolism of cholesterol, and (iii) a cofactor in the feedback inhibition of cholesterol synthesis. Each of these functions is based upon the premise that nonspecific lipid transfer protein (nsLTP) is cytosolic. However, evidence presented in this report suggests that, at least in the case of cultured hepatoma cells, nsLTP is secreted. This conclusion is supported by three observations. First, after culture of hepatoma cells for 10 h, 88% of the nsLTP (as judged by its phosphatidylethanolamine transfer activity) appears in the medium, whereas the cytosolic level of transfer activity remains unchanged. Furthermore, this is accompanied by the appearance in the medium of a polypeptide of Mr 12,200-12,500, which corresponds to the known molecular weight of nsLTP. Finally, it was observed that the appearance of both the activity and the polypeptide in the medium are inhibited by monensin, an inhibitor of secretion. Thus their appearance seems to represent secretion and not simply leakage from the cells. Further evidence that nsLTP does not play an important role in the cytosolic transport of phospholipid and sterol is provided by our observation that hepatoma cells containing a level of nsLTP only 10-15% of that found in liver nevertheless possess near-normal membrane phospholipid compositions and retain the ability to feedback-inhibit cholesterol biosynthesis. PMID- 4026321 TI - Rabbit antibodies against the human milk sialyloligosaccharide alditol of LS tetrasaccharide a (NeuAc alpha 2-3Gal beta 1-3GlcNAc beta 1-3Gal beta 1-4GlcOH). AB - The sialyloligosaccharide, NeuAc alpha 2-3Gal beta 1-3GlcNAc beta 1-3Gal beta 1 4Glc (LS-tetrasaccharide a), a minor component of human milk, is obtained in relatively large quantities from autohydrolysates of the major milk disialyloligosaccharide, NeuAc alpha 2-3Gal beta 1-3[NeuAc alpha 2-6]GlcNAc beta 1-3Gal beta 1-4Glc (disialyllacto-N-tetraose). Rabbits immunized with an oligosaccharide-protein conjugate prepared from keyhole limpet hemocyanin and LS tetrasaccharide a produce antibodies directed against the corresponding oligosaccharide alditol. The anti-LS-tetrasaccharide a sera bind 3H-labeled LS tetrasaccharide a in a direct-binding radioimmunoassay on nitrocellulose filters. The specificities of these antibodies are determined by comparing inhibitory activities of structurally related oligosaccharides. Strong hapten-antibody binding (Ka greater than 10(6) M-1) requires sialic acid linked alpha 2-3 to the nonreducing terminal galactose residue of reduced lacto-N-tetraose (Gal beta 1 3GlcNAc beta 1-3Gal beta 1-4GlcOH). Specificities of antibodies prepared against keyhole limpet hemocyanin conjugates of LS-tetrasaccharide b (Gal beta 1-3[NeuAc alpha 2-6]GlcNAc beta 1-3Gal beta 1-4Glc) and LS-tetrasaccharide c (NeuAc alpha 2 6Gal beta 1-4GlcNAc beta 1-3Gal beta 1-4Glc) differ only slightly from rabbit antibodies prepared against the corresponding bovine serum albumin conjugates described previously [D. F. Smith and V. Ginsburg (1980) J. Biol. Chem. 255, 55 59]. PMID- 4026322 TI - Multiple molecular forms of diarylpropane oxygenase, an H2O2-requiring, lignin degrading enzyme from Phanerochaete chrysosporium. AB - Three different molecular forms of the H2O2-requiring heme enzyme, diarylpropane oxygenase, were isolated from the extracellular medium of Na-acetate buffered, agitated cultures of Phanerochaete chrysosporium. Forms I, II, and III were separated by DEAE-Sepharose and further purified on Sephadex G-100. Absorption maxima of the native, reduced, and a variety of ligand complexes of the three enzyme forms are essentially identical, indicating similar heme environments. All forms also have similar, but not identical, reactivity. The homogeneous proteins oxidized a diarylpropane, an olefin, a beta-aryl ether dimer, a phenylpropane, phenylpropane diols, and veratryl alcohol. Identical products were produced from each form. However, the specific activities of the three homogeneous enzymes for veratryl alcohol oxidation were 18.75, 11.80, and 8.48 mumol min-1 mg-1. In the presence of one equivalent of H2O2 the Soret maximum of diarylpropane oxygenase II shifted from 408 to 418 nm, and two additional maxima appeared at 526 and 553 nm, indicating the presence of an Fe(IV)-oxo species equivalent to horseradish peroxidase II. This oxidized species could be reduced back to the native form by veratryl alcohol and several reducing agents (e.g., Na2S2O4, NH2NH2, thiourea, or NADH). The molecular weights of diarylpropane oxygenases I, II, and III were approximately 39,000, 41,000, and 43,000, respectively. The major form (II) (85% of the activity) contained approximately 6% neutral carbohydrate. The affinity of the forms for concanavalin A-agarose suggests that they all are glycoenzymes. PMID- 4026323 TI - Diethylpyrocarbonate inactivation of NAD-malic enzyme from Ascaris suum. AB - Treatment with diethylpyrocarbonate results in a first-order loss of the malate oxidative decarboxylase activity of NAD-malic enzyme. First-order plots are biphasic, with about 40-50% activity loss in the first phase. The inactivation process is not saturable, and the second-order rate constant is 4.7 M-1 S-1. Malate (250 mM) provides complete protection against inactivation (as measured by a decrease in the inactivation rate), and less malate is required with Mg2+ present. Partial protection (50%) is afforded by either NAD+ (1 mM) or Mg2+ (50 mM). Treatment of modified (inactive) enzyme with hydroxylamine restores activity to 100% of the control when corrected for the effect of hydroxylamine on unmodified enzyme. A total of 10-13 histidine residues/subunit are acylated concomitant with loss of activity while 1-2 tyrosines are modified prior to any activity loss. The presence of Mg2+ and malate at saturating concentrations protect 1-2 histidine residues/subunit. The intrinsic fluorescence of the enzyme decreases with time after addition of diethylpyrocarbonate, but the rate constant for this process is at least 10-fold too low to account for the biphasicity observed in the first order plots. The histidine modified which is responsible for loss of activity has a pK of 8.3 as determined from the pH dependence of the rate of inactivation. The histidine titrated is still modified under conditions where the residue is completely protonated but at a rate 1/100 the rate of the unprotonated histidine. The results suggest that 1-2 histidines are in or near the malate binding site and are required for malate oxidative decarboxylation. PMID- 4026324 TI - Effects of glutathione depletion on gluconeogenesis in isolated hepatocytes. AB - Glutathione-depleted hepatocytes, by incubation with diethylmaleate (DEM) or phorone (2,6-dimethyl-2,5-heptadiene-4-one), i.e., substrates of the GSH S transferases (EC 2.5.1.18), showed rates of gluconeogenesis from various precursors significantly lower than controls; however the rate of glucose synthesis from fructose was similar to that of controls. Isolated hepatocytes from rats pretreated with those substrates 1 h before isolation to deplete hepatic glutathione (GSH) also showed a decrease of the rate of gluconeogenesis from lactate plus pyruvate. Incubation of hepatocytes with L-buthionine sulfoximine, a specific inhibitor of gamma-glutamyl-cysteine synthetase (EC 6.3.2.2), resulted in a decreased rate of gluconeogenesis from lactate plus pyruvate only when GSH values were lower than 1 mumol/g cells. Freeze-clamped livers from GSH-depleted rats showed a higher concentration of malate and glycerol 3-phosphate, indicating that GSH depletion probably affects phosphoenolpyruvate carboxykinase and glycerol-3-phosphate dehydrogenase activities. Several indicators of cell viability, such as lactate dehydrogenase leakage, malondialdehyde accumulation, ATP concentration, or urea synthesis from different precursors, were not affected by GSH depletion under the experimental conditions used here. Besides, the GSH/GSSG ratio remained unchanged in all cases. PMID- 4026325 TI - Evidence for lipid involvement in the high-affinity interaction between cimetidine and rat liver cytochrome P-450. AB - The spectral interaction between cimetidine and a cytochrome P-450 fraction isolated from liver of untreated rats has been shown to be markedly affected by dilauroylphosphatidylcholine. In the absence of the lipid the pigment preparation yielded a binding curve characteristic of a single isoenzyme species with low affinity for the drug, whereas its inclusion led to the observation of a much stronger interaction with a dissociation constant close to that obtained for the high-affinity component(s) of the parent microsomes; material with lower affinity was also observed. Gel chromatography and partition equilibrium studies yielded results which precluded interpretation of this finding either in terms of incomplete incorporation of the pigment into the phospholipid or of disproportionate solvation of cimetidine into the lipid phase of the reconstituted phospholipid complex. In contrast, phospholipid caused only a minor change in the strength of cimetidine binding by the predominant liver cytochrome P-450 from phenobarbitone-pretreated rats. Pronounced lipid sensitivity of cimetidine-binding affinity is thus not a general feature of the microsomal cytochrome P-450 system but rather a specific characteristic of individual isoenzyme species. PMID- 4026326 TI - Inhibition of microsomal lipid peroxidation by naphthoquinones: structure activity relationships and possible mechanisms of action. AB - Menadione (2-methyl-1,4-naphthoquinone) is a remarkably potent inhibitor of microsomal lipid peroxidation, effective at submicromolar concentrations. Its possible mechanism of action and the relationship between naphthoquinone structure and antioxidant activity were the topics of this investigation. In the microsomal lipid-peroxidizing system dependent on NADPH and ferric pyrophosphate, menadione, at concentrations of 50 microM or higher virtually eliminated the accumulation of malondialdehyde and lipid hydroperoxides. In the NADPH independent, cumene hydroperoxide-dependent system, menadione was also an effective antioxidant, but only in the presence of reducing equivalents. These and other observations indicate that a reduced form of menadione, either the hydroquinone or semiquinone, is the active antioxidant, and suggest that it may trap hydroperoxy radicals, alkoxy radicals, or other free radicals involved in propagating lipid peroxidation. Moreover, these results show that electron diversion per se cannot account for the antioxidant effects of menadione. A comparison of the antioxidant activities of eight 1,4-naphthoquinones indicated that methyl substitution of C-2, lack of steric hindrance at C-3 or C-5, and (in the case of weak acids) a relatively high pKa are favorable structural features associated with strong antioxidant activity. PMID- 4026328 TI - [Current status of the human tumor clonogenic assay for gastrointestinal cancer]. AB - The author reviewed his experience to date with chemosensitivity testing of 162 gastric and 144 colorectal cancers. All human tumor clonogenic assays were performed using a double-layer soft agar system with continuous exposure of cells to one concentration of standard anticancer drugs. Significant growth was defined as greater than or equal to 30 colonies/control plate. Clinical responses were determined according to standard criteria. Forty-six per cent of gastric cancer specimens and 67% of colorectal cancer specimens plated produced significant growth in vitro. When greater than or equal to 50% inhibition of colony formation was used as the criterion for differentiating sensitivity from resistance, the assay was 67% (8/12) reliable for predicting in vivo sensitivity, and 91% (10/11) reliable for in vivo resistance. PMID- 4026327 TI - Isolation and characterization of mannan-binding proteins from chicken liver. AB - Two binding proteins which recognize and bind mannose and N-acetylglucosamine (mannan-binding proteins, MBP) have been isolated from chicken liver to near homogeneity mainly by affinity chromatography on a column of Sepharose 4B-mannan. The neutral binding protein (pI 7.0), which has a high glycine content, is an analog of mammalian liver MBP (F-I). F-I consists of a series of proteins composed of two subunits of 28,000 (A) and 32,000 (B) Da. The proteins have molecular weights ranging from 280,000 to 740,000 and subunit compositions ranging from 6A + 4B to 5A + 19B. With increasing molecular weight the specific activity of mannan binding increases gradually, accompanied by a slight change in specificity to a preference for mannose rather than N-acetylglucosamine. The acidic binding protein (pI 5.1) is a glycoprotein with a high glutamic acid content (F-II). The molecular weight of F-II was estimated to be 640,000, and it is composed of single subunits of 41,000 Da. The two MBPs isolated in this study are distinct from the liver lectin specific for N-acetylglucosamine-terminated glycoproteins isolated from the same source [T. Kawasaki and G. Ashwell (1977) J. Biol. Chem. 252, 6536-6543] in chemical properties and binding specificities. PMID- 4026329 TI - [Effect of preoperative intra-arterial infusion of adriamycin on locally advanced breast cancer]. AB - The effect of adriamycin (ADM) infused intraarterially as a preoperative procedure was analyzed retrospectively in 15 patients with primary advanced breast cancer. A high clinical response rate (CR+ PR) of 73% (11/15) was obtained by the treatment, and also remarkable degenerative changes of tumor cells were histologically noted in 10 out of 15 surgical specimens (67%). A correlation between the dose of ADM infused and the rate of tumor regression was observed. A significantly higher concentration of ADM was detected in metastatic lymph nodes and tumors obtained 3-4 weeks after intra-arterial infusion of ADM than that in normal mammary gland. As for side effects, alopecia, leukocytopenia, anorexia, nausea and vomiting occurred at high frequencies. The side effects due to this treatment were considered to be tolerable. Prognostically, a good survival rate was not observed using preoperative treatment with intra-arterial ADM infusion. PMID- 4026330 TI - [Experience in local hyperthermia with using ThermaTech 2000--second report]. AB - In the use of hyperthermia treatment, it is apparent from the work of other investigators that only a proportion of large clinical neoplastic tumors of substantial size and deep location can be heated to adequate temperatures (over 42 degrees c). It is therefore of major significance that we have tested the concept that OK-432 can be used as an immunoheat potentiator. A ThermaTech 2000 was used as the radio-frequency generator at 13.56 MHz, including an ancillary computer in the thermometry unit. Minor response in advanced and metastatic tumors was observed in 3 of 3 evaluable patients using OK-432. With other anticancer drugs, no change was observed in 11 of 16 patients, and progressive disease in 5 of 16. However, OK-432 has severe side effects including chills & fever, therefore improved immunoheat potentiators are desirable. PMID- 4026331 TI - [Microvascular architecture of human gastrointestinal and breast cancer xenografts in nude mice, and its relation to chemosensitivity]. AB - As a tumor factor possibly responsible for chemosensitivity of human cancer xenografts in nude mice, the vascular architecture of tumors growing in mice was investigated in 15 kinds of cancer lines. These consisted of 7 gastric, 3 colorectal, 3 breast and 2 pancreatic cancers. Whole body angiograms of tumor bearing mice were obtained by perfusing a radiopaque silicone rubber compound (Microfil) through the left ventricle of each mouse. Each cancer retained a characteristic vascular architecture comparable to its histopathological finding. According to the vascularity of the viable part of the tumor, the 15 lines of cancer were classified into 5 groups. Compared with colorectal cancers, stomach cancers had a tendency to decline to a more hypervascular group. There was no apparent relation between vascularity and growth rate, or histological differentiation of the tumors. Among 14 anticancer agents studied, statistically significant correlation between chemosensitivity and vascularity of the 15 cancer lines was observed in 2 drugs, 5'-DFUR and adriamycin. The vascular architecture of the tumors would have some influence in their chemosensitivity through drug accessibility to cancer cells. PMID- 4026332 TI - [Changes in tumor transvascular pressure difference associated with tumor growth: implications for angiotensin-induced hypertension chemotherapy]. AB - In order to further elucidate the mechanism of drug delivery to tumor tissue, changes in tumor vessel pressure and interstitial fluid pressure associated with tumor growth were measured by means of a compression method and a micro-occlusion method and a diffusion chamber method, respectively. Tumor interstitial fluid pressure was always positive and much higher than that in the normal subcutis. Furthermore the pressure became higher as the tumor mass grew. Conversely, tumor vessel pressure was reduced with tumor growth. Increase in the interstitial fluid pressure and slight decrease in the tumor vessel pressure should together result in a reduction of the hydrostatic pressure difference between the intravascular and extravascular space of the tumor, which seems to be one of the important factors influencing fluid exchange and drug delivery. However, the transvascular pressure gradient in the tumor was increased under angiotensin-induced hypertension, resulting in advantageous conditions for drug delivery. PMID- 4026333 TI - [Analysis of chemosensitivity against a human breast cancer xenograft (MX-1) with the subrenal capsule assay in BDF1 mice]. AB - The antitumor activity of 27 anticancer drugs against a human breast cancer tumor (MX-1) has been studied using the subrenal capsule assay developed by A.E. Bogden et al. in 1978. Without immunosuppression with cyclophosphamide, BDF1 mice transplanted with MX-1 were treated with various drugs. The antitumor activity was evaluated by the tumor growth inhibition rate on day 6 after treatment. Among the 27 anticancer drugs tested, 10 compounds (37%) which showed more than 75% tumor growth inhibition rate were considered to be active. On the other hand, 8 compounds out of 27 drugs (30%) which showed less than 50% tumor growth inhibition rate were considered to be inactive. When the antitumor activity between the subrenal capsule assay in BDF1 mice and the subcutaneous transplantation assay in nude mice were compared, both assays were well correlated (r = 0.787, p less than 0.001). These results suggest that the antitumor activity of drugs can be evaluated faster, cheaper and easier by the subrenal capsule assay compared with the subcutaneous transplantation assay in nude mice. PMID- 4026334 TI - [Change of acid phosphatase activity in granulocytes from patients with carcinomas of the gastrointestinal tract]. PMID- 4026335 TI - Neutral lipid storage disease with ichthyosis. Defective lamellar body contents and intracellular dispersion. AB - Although the link between epidermal lamellar body lipids and stratum corneum barrier function is well established, a role for lamellar body lipids in desquamation remains unproved. We examined skin biopsy material from three family members of a Palestinian kindred with a multisystem disorder of altered lipid metabolism, ichthyosis, and deposition of fat droplets in multiple tissues (Chanarin-Dorfman syndrome, neutral lipid storage disease). Thin-section and freeze-fracture ultrastructural studies revealed a distinctive lamellar body abnormality: multilaminated spherules that distorted and displaced the normal internal disk structure of these organelles. Whereas these spherules remained interspersed with secreted lamellar body contents within the intercellular spaces of the outer epidermis, at the stratum granulosum-stratum corneum interface they apparently dispersed into electron-lucent "slits." These studies therefore provide strong support for the concept that lamellar body-derived lipids influence stratum corneum desquamation and further suggest that abnormalities of neutral lipid-alkane metabolism influence normal epidermal shedding. PMID- 4026336 TI - Hair casts. A clinical and morphologic study. AB - Idiopathic hair casts are described in two girls aged 5 and 7 years. A 0.025% tretinoin lotion seemed effective in removing the casts. Investigations, including light microscopy and transmission electron microscopy, suggest an infrainfundibular origin for these lesions, because both inner and outer root sheath components were observed in the transverse sections of the casts. A comprehensive review of the literature enabled us to classify the patients into two distinct groups: group 1 consisted of patients with idiopathic disease, showing a diffuse pattern of involvement, and group 2 consisted of patients with disease secondary to a variety of inflammatory scalp disorders. PMID- 4026337 TI - Dystrophic epidermolysis bullosa. A new variant characterized by progressive symmetrical centripetal involvement with scarring. AB - A patient is reported with a form of epidermolysis bullosa, hitherto undescribed to the best of our knowledge, characterized by the slow centripetal progression of symmetrical blister formation, milia, scarring, atrophy, and nail dystrophy. Electron microscopy, immunofluorescence mapping, and KF-1 monoclonal antibody studies confirm this disease to be a form of dystrophic epidermolysis bullosa, probably of autosomal recessive transmission despite the absence of acral deformities, contractures, mucosal involvement, and growth retardation. PMID- 4026338 TI - Yellow staining caused by 4,4'-methylenedianiline exposure. Occurrence among molded plastics workers. AB - Workers engaged in a molded plastics operation were studied to determine the etiology of yellow staining reactions involving the skin, nails, and hair. A walk through survey of the facility, medical interviews, physical examinations, and blood and urine tests were performed. 4,4'-Methylenedianiline (MDA), a component chemical of the manufacturing process, produced intense yellow discoloration of nitrocellulose paper in the laboratory and appeared to volatilize readily under ambient conditions. Thirty-five (65%) of 54 process workers showed varying degrees of staining while 11 workers employed in other parts of the factory showed no staining. Yellow staining was restricted to areas of the body where direct contact with MDA appeared likely. Laboratory studies did not provide evidence of systemic toxic effect. Because MDA is a known hepatotoxin for man, with carcinogenic properties in animal test systems, it is important to recognize yellow staining as a cutaneous marker of exposure to this chemical. PMID- 4026339 TI - Perifolliculitis capitis abscedens et suffodiens (Hoffman). Complete healing associated with oral zinc therapy. AB - A 24-year-old man with a one-year history of perifolliculitis capitis abscedens et suffodiens (Hoffman) was treated with oral zinc sulfate. Complete healing was seen after three months and the treatment was continued for a total of six months. No relapse has occurred during a five-year follow-up. The mechanisms through which zinc therapy might influence inflammatory conditions are not fully understood. PMID- 4026341 TI - Congenital arrector pili hamartoma. A case report and review of the spectrum of Becker's melanosis and pilar smooth-muscle hamartoma. AB - Congenital pigmented arrector pili hamartomas are unique malformations of epidermis and pilar apparatus usually appearing as localized, lightly pigmented, hairy plaques. Characteristic microscopic features include smooth-muscle proliferation similar to irregularly disposed arrectores pilorum, and slight elongation of epidermal rete with hypermelanosis of the basal unit. An otherwise normally developed child who had this hamartoma at birth is described in an attempt to clarify the relationship between pilar smooth-muscle hamartomas and Becker's melanosis. We propose that these two entities belong at different poles of the same developmental spectrum of hamartomatous change. PMID- 4026342 TI - Pseudo-Kaposi's sarcoma of the hand associated with an acquired, iatrogenic arteriovenous fistula. AB - Pseudo-Kaposi's sarcoma has been associated, in most cases, with an underlying congenital arteriovenous (AV) fistula. A patient with chronic renal failure and an acquired, iatrogenic AV fistula in his left wrist for hemodialysis developed pseudo-Kaposi's sarcoma on his left hand three years after placement of the AV fistula. Histologic findings included a proliferation of superficial dermal vessels and fibroblasts, extravasated red blood cells, and occasional fibrin thrombi in vessels. To our knowledge, this is the third case of an association between pseudo-Kaposi's sarcoma and an acquired, iatrogenic AV fistula, and the first to involve the hand. Pseudo-Kaposi's sarcoma occurs in association with underlying congenital and acquired AV fistulas. PMID- 4026340 TI - Acquired progressive kinking of hair. Report of six cases and review of literature. AB - Acquired progressive kinking of hair is an entity distinct from woolly hair in its onset at or after puberty, predominant involvement of frontal, temporal, and vertex regions of the scalp as well as the supra-auricular and postauricular margins, and a tendency for affected hairs to resemble pubic hair both in texture and color. We consider the condition to be androgen dependent and likely to progress to male pattern baldness. The condition "whisker hair" is probably a variant of acquired progressive kinking of hair. PMID- 4026343 TI - Epidermotropic metastatic squamous cell carcinoma. Report of two cases showing histologic continuity between epidermis and metastasis. AB - Two unusual cases of squamous cell carcinoma (SCCa) metastatic to skin from distant sites occurred. In both metastatic sites, the malignant squamous epithelium fused with benign surface epithelium, and the resulting transition simulated that typically seen in primary cutaneous SCCa. We believe that this previously unreported phenomenon is an expression of the natural tendency of squamous epithelium to "heal" denuded connective tissue surfaces by proliferation followed by epithelial fusion. Because epithelial continuity can be established between benign keratinocytes and metastatic SCCa, one cannot rely on this single morphologic finding to separate primary from metastatic disease. PMID- 4026344 TI - Lichen sclerosus et atrophicus following radiation therapy. AB - Several years after postmastectomy radiation therapy, lichen sclerosus et atrophicus (LSA) developed in two patients within the radiation fields. This sequence, to our knowledge, has not previously been described. The etiology of LSA is largely unknown, but trauma has been implicated as a provoking factor in some cases, and LSA might be an isomorphic response to the trauma of radiation therapy. PMID- 4026345 TI - A syndrome with nodular erythema, elongated and thickened fingers, and emaciation. AB - A 5-year-old boy had a nodular erythema, elongated and thickened fingers, and emaciation. His condition was a rare congenital disease inherited as an autosomal recessive trait. Eleven cases have been previously reported in the Japanese literature. The onset is early in childhood, and nodular erythema is an essential and initial finding. Growth retardation and emaciation progress slowly with age. The characteristic clinical features include large eyes, nose, lips, and ears, disproportionately long and thick fingers, and the loss of adipose tissue from the upper half of the body. Cardiomegaly and hypertrophy of the periosteum of the phalanges have been described in some cases. PMID- 4026346 TI - Juvenile hyaline fibromatosis. A 15-year follow-up. AB - A 37-year-old man was seen because of juvenile hyaline fibromatosis that had been present since he was 2 to 3 years old. His case illustrates the progressive nature of the disease, and during the years attempts to treat the condition were as mutilating in some cases as the disease itself. PMID- 4026347 TI - Acute skin manifestations of Conradi-Huenermann syndrome in a male adult. AB - A man displayed the acute inflammatory cutaneous manifestations and the late "incontinentia pigmenti-like" lesions of Conradi-Huenermann subgroup B of chondrodysplasia punctata. The case appears as unique in the literature in that, to our knowledge, both kinds of skin changes have been described only in newborns or early in infancy. PMID- 4026349 TI - Removal of congenital nevocytic nevi. PMID- 4026348 TI - Cutaneous protothecosis presenting as recurrent chromomycosis. AB - Chromomycosis and protothecosis are both rare cutaneous infections. We report a case in which protothecosis mimicked a relapse of chromomycosis both clinically and on special stains. The chromomycosis responded to local excision and ketoconazole therapy. The protothecosis failed to respond to ketoconazole but resolved with combined amphotericin B and tetracycline hydrochloride therapy. PMID- 4026350 TI - Hypothyroidism, insulin resistance, and acanthosis nigricans. PMID- 4026351 TI - Pigmentatio reticularis faciei et colli. PMID- 4026352 TI - Proliferation of melanocytes in keratoacanthoma. PMID- 4026353 TI - Kaposi's sarcoma localized to the site of previous vascular surgery. PMID- 4026354 TI - The double-edge knife. PMID- 4026355 TI - Application of topical corticosteroids. PMID- 4026356 TI - Effect of varying water intake on renal function in healthy preterm babies. AB - Renal control of water and electrolyte homeostasis was studied in 10 healthy babies (gestation 29 to 34 weeks; birthweight 1.19 to 2.19 kg) while water intake was varied. Glomerular filtration rate and urine flow were estimated daily from spot plasma and urine samples for six days using a constant inulin infusion, and simultaneous sodium, potassium, osmolar, and free water clearances were calculated. The infusion was started at an average age of 14 hours. Each baby received a total fluid intake of 96 ml/kg daily on study days 1, 2, and 5, and about 200 ml/kg on study days 3, 4, and 6. Daily sodium intake was kept constant at 3 mmol/kg. At the end of the first study day the babies were undergoing a diuresis, but thereafter their estimated daily water balances remained stable regardless of intake. Glomerular filtration remained stable; alterations in urine flow reflected a change in the percentage of filtrate excreted. Plasma electrolytes and osmolality were stable throughout, and on study days 2 to 6 the urinary excretion rates of sodium, potassium, and other osmoles remained the same regardless of urine flow. The delivery of sodium to the distal tubule was estimated to be between 17 and 20% of the filtered load. Well preterm babies can cope with daily water intakes between 96 and 200 ml/kg from the third day of life. PMID- 4026357 TI - Renal response to frusemide in preterm infants with respiratory distress syndrome during the first three postnatal days. AB - The renal effects of frusemide treatment in infants with respiratory distress syndrome shortly after birth and during the first three postnatal days were evaluated. Eighty five infants were randomly assigned to two groups. Forty two received three doses of intravenous frusemide (1 mg/kg) starting at age, mean (SD) 7.5 (4.1) hours and given at approximately 24 hour intervals. Forty three control infants were treated similarly but were not given frusemide. The groups were comparable in birthweight, gestational age, and Apgar score and in pulmonary status, blood gases, serum electrolytes, and postnatal age. Infants who received frusemide had significantly higher fractional excretion of sodium and chloride at 12 to 24, 24 to 48, and 48 to 72 hours, and higher calcium excretion at 24 to 48 and 48 to 72 hours after entry into the study than control infants. The study group had a significantly higher urine output and greater weight loss than the control group at 48 to 72 hours after entry into the study. There was no significant difference between groups in serum sodium, potassium, and calcium and in fractional excretion of potassium and the glomerular filtration rate. Infants with an Apgar score of more than 3 had higher urine output and had a better diuretic response to frusemide than those with a lower score. The results suggest that perinatal hypoxia may play an important role in renal function and in diuretic response to frusemide shortly after birth and early in the postnatal life of infants with respiratory distress syndrome. PMID- 4026359 TI - Admission to hospital with asthma. AB - The circumstances surrounding 142 hospital admissions for acute asthma in 110 children during a one year period were examined. Thirty four of 106 (32%) children with previous wheezing had not been diagnosed as asthmatic, nor received effective antiasthmatic medication. Nineteen of 36 (53%) known, but undertreated, asthmatics were under the care of the hospital paediatricians. Twenty-four of 58 (41%) regular school attenders had missed more than 11 days' school in the previous year. Good parental understanding of their child's illness was strongly associated with adequate treatment. Parental understanding was, however, poor in 58 of 137 (42%) admissions. Control of inadequately treated chronic symptoms was obtained by simple and straightforward changes in treatment. PMID- 4026358 TI - Factors associated with the blood pressures of children born to women who were hypertensive during pregnancy. AB - At age 7.5 years the supine blood pressures of 216 children born to women who had been hypertensive during pregnancy were recorded. No associations were found between the blood pressures of the children and their mothers. The blood pressures of children whose mothers received methyldopa during pregnancy did not differ from those of children whose mothers had no specific treatment. Four boys whose mothers had taken methyldopa for more than 150 days had significantly lower systolic and diastolic pressures than those in whom the treatment had been of shorter duration. Significant findings from multiple regression analyses were: positive associations between boys' systolic and diastolic pressures and current weight, and diastolic pressure and maternal weight; negative associations between boys' systolic and diastolic pressures and birthweight; and a positive association between girls' systolic pressure and current weight. PMID- 4026360 TI - Copper deficiency in the preterm infant of very low birthweight. Four cases and a reference range for plasma copper. AB - Four preterm infants of very low birthweight (less than 1500 g) developed signs of copper deficiency between age 8 and 10 weeks. All had required prolonged ventilatory support, parenteral nutrition, and nasojejunal feeding. The clinical features, which included osteoporosis, oedema, anaemia, neutropenia, and late apnoea improved when the oral copper intake was increased. Diagnosis was made more difficult because a suitable reference range for plasma copper was not available. Serial measurements of plasma copper in 39 preterm infants who had no important medical problems were used to produce a reference range for plasma copper from 30 weeks' gestation to term plus seven weeks. This information will aid recognition of hypocupraemia in the very low birthweight infant who is particularly at risk of copper deficiency. PMID- 4026361 TI - Wilson's disease: assessment of D-penicillamine treatment. AB - Serum copper and zinc concentrations and 24 hour urinary copper and zinc excretion were determined serially from the beginning of treatment with D penicillamine in four children with Wilson's disease. The data show a progressive decrease in both serum copper and zinc concentrations in all. Urinary copper excretion gradually levelled off to approximately 50% of initial values, but zinc excretion increased. Urinary zinc:copper ratios therefore increased with the duration of treatment. Copper elimination was considered adequate as soon as challenge with a test dose of D-penicillamine did not result in an increase in copper excretion. Urinary zinc excretion was increased further by the test dose. Zinc depletion was suspected clinically in one patient on D-penicillamine maintenance treatment. Lowering the dose alleviated the symptoms, urinary zinc loss decreased from 64 to 34 mumol/24 hours, and copper excretion remained largely unchanged. Data obtained indicate that D-penicillamine alters the metabolism of both copper and zinc. The extent of this is not only dose dependent but is also related to the efficacy of copper elimination. Both copper and zinc concentrations must by monitored to assess the benefits of treatment and the risks of inducing manifest or subclinical zinc deficiency. PMID- 4026362 TI - Oral zinc sulphate for Wilson's disease. AB - After initial promotion of copper excretion with D-penicillamine, the effect of oral zinc sulphate (3 X 150 mg/day, loading dose; 3 X 100 mg/day, maintenance dose) in two children with clinically stable Wilson's disease was evaluated after completion of three years' treatment. The course, judged by clinical, biochemical, and histological parameters was satisfactory in both. The urinary copper concentration reverted to less than 1.26 mumol/24 hours; and the serum copper concentration decreased further during zinc sulphate treatment. In one child the rise in 24 hour urinary copper excretion observed after a challenge dose of D-penicillamine (+/- 20 mg/kg) remained constant throughout the period of observation while the liver copper content fell from 1460 micrograms/g dry weight to 890 micrograms/g dry weight. In the other patient, however, the liver copper content as well as the 24 hour urinary copper excretion increased after D penicillamine challenge during the third year of treatment. We conclude that zinc sulphate is a low toxic and well tolerated alternative for D-penicillamine. The dosage depends, however, on individual factors not yet well understood, and we recommend restriction of its use to patients who do not tolerate D-penicillamine well. We suggest monitoring of treatment with yearly D-penicillamine challenge and a liver biopsy if liver function deteriorates. PMID- 4026363 TI - Maternal serum folate and vitamin B12 concentrations in pregnancies associated with neural tube defects. AB - Serum folate and vitamin B12 concentrations in early pregnancy were compared for 32 mothers with pregnancies affected by neural tube defects and 395 randomly selected pregnant control women from the same maternity hospitals. No significant differences were found between the affected mothers and the controls in the median values and frequency distributions of either vitamin. Sixteen of the samples from mothers whose infants had neural tube defects were taken between 9 and 13 weeks' gestation and 11 of these had both serum folate and vitamin B12 concentrations within the normal ranges for our laboratory. These findings are discussed in relation to the concept of folate deficiency as a major factor in the aetiology of neural tube defects. PMID- 4026364 TI - Rectal examination and acute appendicitis. AB - A correct diagnosis of acute appendicitis was made in 90% of 103 children on the basis of history and abdominal findings. Preoperative rectal examination altered management only twice, and postoperatively was a poor indicator of pelvic sepsis. PMID- 4026365 TI - Intravenous immunoglobulin for neonatal isoimmune thrombocytopenia. AB - An infant with severe, isoimmune thrombocytopenia secondary to maternal anti-Pla 1 immunisation was treated successfully by intravenous gammaglobulin (400 mg/kg per day for five days). This treatment compared with Pla 1 negative platelet transfusions is discussed. PMID- 4026366 TI - Inguinal hernias are common in preterm infants. AB - The incidence of inguinal hernia was compared in term and preterm infants. The risk was considerably higher in the preterm group in both sexes. No particular complications of preterm birth were found to predispose to inguinal hernia. PMID- 4026367 TI - Recurrent infections with IgG2 deficiency. AB - An 11 year old girl with retarded growth, recurrent infections, bronchiectasis, and normal serum immunoglobulin concentrations had a combined deficit of the IgG2 subclass and IgG and IgM specific antibodies. Immunoglobulin replacement was followed by clinical improvement. The importance of determining both IgG subclasses and antibody activity in patients with recurrent infections and normal serum immunoglobulin values is emphasised. PMID- 4026368 TI - Parents' understanding of coeliac disease and diet. AB - Parents of 50 children with coeliac disease were questioned about their knowledge of the disorder and the child's dietary compliance. Twenty of 50 parents admitted that compliance was less than strict. This correlated with poor knowledge of the disease which in turn was related to the family's social status. Membership of the Coeliac Society (23 of 50) correlated with both parental understanding and dietary compliance. Greater emphasis on dietary compliance and education of parents and patients is required. PMID- 4026369 TI - Prevention of spread of echovirus 6 in a special care baby unit. AB - A case of fatal neonatal infection with enteric cytopathogenic human orphan virus (echovirus) type 6 is presented. The measures taken to prevent further spread of infection with special reference to the use of human normal immunoglobulin are described. PMID- 4026370 TI - Neonatal urinary ascites. AB - Two neonates with spontaneous rupture of the bladder and an otherwise normal genitourinary tract are described. Conservative management resulted in complete resolution of the lesion in one but the other child died from a coliform septicaemia. Necropsy showed a discrete ischaemic lesion in the fundus of the bladder. PMID- 4026371 TI - Passenger safety in cars. AB - Comparison of child passengers between January 1983 and 1984 showed an increased use of rear safety restraints after the wearing of front seat belts became mandatory. In 1984, however, only 25% of children were restrained, most commonly in a safety seat. PMID- 4026372 TI - Hysteria. PMID- 4026373 TI - Metabolic bone disease in preterm infants. PMID- 4026374 TI - Coagulation disturbances and fulminant liver failure. PMID- 4026375 TI - Munchausen's syndrome and child psychiatrists. PMID- 4026377 TI - Mast cells and macrophages in early relapsing psoriasis. AB - Five patients with widespread plaque-type psoriasis were treated continuously with clobetasol under occlusion. Clinical healing was seen after 6-10 days of treatment. All plaques treated in this way clinically relapsed approximately 12 days later. During the period of remission, sequential biopsies were taken and prepared for light and electron microscopy. Histologically, the earliest indications of relapse were endothelial alterations (swelling, intercellular widening) followed by the appearance of mast cells around the postcapillary venules; these mast cells showed signs of degranulation. Hours later, activated macrophages showing pericellular edema were present, and these migrated into the epidermis soon after. Associated with the presence of macrophages, there was a complete loss of desmosome-tonofilament complexes. Later, lymphocytes and neutrophils were seen. Under these experimental conditions, the psoriatic-tissue alterations appear to have been initiated by degranulating mast cells as well as by macrophages which later invaded the epidermis. PMID- 4026376 TI - IgA anti-endomysial antibody detection in the serum of patients with dermatitis herpetiformis following gluten challenge. AB - This study reports the appearance of IgA-class anti-endomysial antibodies in the serum of 8 out of 12 patients with dermatitis herpetiformis who were challenged with gluten after a number of years of control of the rash with a strict gluten free diet. Although there was no evidence for the antibodies having any pathogenic role in the rash of dermatitis herpetiformis, their presence may be related to the deterioration in the gluten-sensitive enteropathy. PMID- 4026378 TI - Nevoid malignant melanoma. AB - Primary cutaneous malignant melanomas with histological features suggestive of benign nevocytic nevi were studied. From a total of about 3,500 cases, 33 patients with sufficient records, histological slides, and follow-up (at least 5 years for disease-free cases) were found; 15 of them had developed metastases, and 8 had died of disseminated melanoma. Some of the following histological characteristics were always observed: cellular atypia, mitoses, infiltration of adnexa, and in the deeper dermis, infiltrative growth, pigmented tumor cells, sharply demarcated tumor nests, and the absence of maturation. Tumor thickness was the most important prognostic criterion. Clinically, the tumors corresponded to nodular and superficial spreading melanomas. It is concluded that, in rare instances, malignant melanomas strongly resemble benign melanocytic/nevocytic nevi. Such cases do not appear to have a lower degree of malignancy and should be treated as normal malignant melanomas. PMID- 4026379 TI - Collagen synthesis in scleroderma: selection of fibroblast populations during subcultures. AB - In progressive systemic scleroderma, excessive deposition of collagen leads to fibrosis of several tissues including the skin. It has been found that different populations of fibroblasts are present in scleroderma skin; these can be obtained by establishing cell cultures from different layers of the involved skin. Excessive overproduction of collagen was noted in primary cultures of cells obtained from deeper layers of the skin of patients in an early stage of the disease, whereas control fibroblasts did not manifest significant variations dependent on the layers of skin used to initiate the cultures. The synthesis of type-I and -III collagen was found to be altered concomitantly. The production of collagen and collagenous proteins was then followed during subcultivations of overproducing fibroblasts. In many cell strains, increased synthesis of collagen and/or non-collagenous proteins had already been lost after the first subcultivation, whereas overproduction was stable in others. However, after five passages, most of the cultures showed normal collagen synthesis, which probably indicates a loss of phenotype due to successive subcultures or overgrowth by another population of fibroblasts. PMID- 4026380 TI - Deoxythymidine pools in animal and human skin with reference to antiviral drugs. PMID- 4026381 TI - Dystrophic epidermolysis bullosa treated unsuccessfully with oral zinc. PMID- 4026382 TI - Neuropathy target esterase in human lymphocytes. AB - Measurement of neuropathy target esterase activity (NTE) in blood lymphocytes has been suggested as a possible biomonitor for organophosphate-induced delayed polyneuropathy. Human lymphocyte NTE was characterized in vitro according to the sensitivity to several organophosphate inhibitors, which was found similar to that of the nervous system enzyme. Methods for collection, storage, and processing of blood and the NTE assay are described (averaged coefficient of variation of the method is 8%). The mean (+/- SD) value of lymphocyte NTE activity in a caucasian population (108 healthy subjects) was 11.5 +/- 2.5 nMoles/min X mg of protein. No sex or age differences were detected. The averaged intraindividual coefficient of variation was 10.1%. These results suggest the feasibility of the test in clinical conditions, a sufficient reproducibility of the test, and a large interindividual variation. Appropriate baseline values are advisable when using the test to evaluate the effects of an occupational exposure to organophosphorus esters which may cause delayed polyneuropathy. PMID- 4026383 TI - Ultra-weak chemiluminescence of smokers' blood. AB - An extremely sensitive single photon counter was developed that could quantitatively detect very weak, spontaneous light emission from human blood samples. Ultra-weak chemiluminescence intensities of cigarette smokers' blood plasma reached significantly higher levels than those of nonsmokers. Elevated levels of the chemiluminescence of the smokers' plasma returned to the nonsmokers' range within 12 hr after cessation of cigarette smoking. We propose that this higher chemiluminescent property of the smokers' plasma might be somehow related to cigarette smoking-associated health disorders, e.g., carcinogenesis. PMID- 4026385 TI - Investigation of potential health effects associated with well water chemical contamination in Londonderry Township, Pennsylvania, U.S.A. AB - A community health survey was conducted by the Pennsylvania Department of Health in Londonderry Township, Dauphin County, Pennsylvania, in response to concerns about potential health effects associated with residential exposure to chemical contaminants in well water. The data indicate that there were no observable adverse health effects in the exposed group of residents, compared with the control group, which could be ascribed to long-term, low-level exposure to trichloroethylene (TCE) and other volatile organic chemicals. Significantly more individuals in the exposed group than in the control group experienced eye irritation, diarrhea, and sleepiness during the 12-month period prior to the survey. This indicated the possibility of an association of contaminated water with the manifestation of symptoms. It is hypothesized that the increased rate of symptoms observed in the exposed group, when compared to the control group, may have been caused by one or more of the following factors: (1) effect of TCE at a threshold level higher than 28 ppb, (2) effect of a single chemical entity other than TCE, and (3) additive or synergistic effects of several chemicals. It is also possible that there are factors other than water contaminants associated with the recorded symptoms, e.g., stress, that may have had an important influence in the exposed group but not in the control group. PMID- 4026384 TI - Mercury uptake in vivo by normal and acatalasemic mice exposed to metallic mercury vapor (203Hg degrees) and injected with metallic mercury or mercuric chloride (203HgCl2). AB - Levels of mercury in the brain and liver of acatalasemic mice immediately following exposure to metallic mercury vapor or injection of metallic mercury were higher than those found in normal mice. Acatalasemic mice had decreased levels of mercury in the blood and kidneys when the levels were compared with those of normal mice, which indicated that catalase plays a role in oxidizing and taking up mercury. Thus, the brain/blood or liver/blood ratio of mercury concentration in acatalasemic mice was significantly higher than that of normal mice. These results suggest that metallic mercury in the blood easily passed through the blood-brain or blood-liver barrier. The levels of mercury distribution to the kidneys of normal and acatalasemic mice, 1 hr after injection of mercuric chloride solution, were higher than that of normal and acatalasemic mice, respectively, 1 hr after injection of metallic mercury. PMID- 4026386 TI - Pentachlorophenol intoxication: report of a fatal case, with comments on the clinical course and pathologic anatomy. AB - A case of a 33-yr-old man who died following occupational exposure to pentachlorophenol is presented. Postmortem examination revealed cerebral edema and fatty degeneration of the viscera. Review of the literature indicates that the clinical syndrome of poisoning with the compound results from mitochondrial toxicity with derangement of aerobic metabolism. PMID- 4026387 TI - Byssinosis: thromboxane release from human platelets by cotton dust and bract extracts. AB - Extracts of cotton dust and bract induced in vitro release of arachidonic acid metabolite thromboxane A2 (TxA2), a potent bronchoconstricting agent, from human platelets. TxA2 release, determined by radioimmunoassay of the stabile metabolite TxB2, was both time- and dose-dependent. Cotton green bract extract was significantly more potent in releasing TxA2 from human platelets than cotton dust extract or cotton brown bract (field-dried bract) extract, while brown bract extract was least active, which suggests that the etiological agent(s) is of plant origin and not microbial in nature. TxA2 release was shown to be enzyme dependent by inhibition of the reaction by indomethacin (cyclooxygenase inhibitor) and 7-(1-imidazolyl) heptanoic acid (thromboxane synthetase inhibitor). This study is the first to show in vitro platelet TxA2 release by cotton extracts and may provide an explanation for increased concentrations of TxB2, a metabolite of TxA2, in the bronchoalveolar spaces of rabbits exposed to aerosolized cotton dust extract. Platelet aggregation and production of TxA2 may prove to be an important mechanism in the pathogenesis of bronchoconstriction in byssinosis. PMID- 4026388 TI - Baseline level of blood lead concentration among Japanese farmers. AB - Lead concentrations were determined for more than 2500 blood samples (more than 2000 winter samples and approximately 500 summer samples) collected from farmers in various parts of Japan to establish reliable baselines for blood lead levels; the analysis was conducted in a single laboratory to avoid any inter-laboratory errors. Blood lead levels distributed log-normally with a geometric mean (i.e., a geometric standard deviation) of 48.6 micrograms/L (1.51) for males and 32.1 micrograms/L (1.50) for females. The levels observed were among the lowest in the industrialized countries of the world. The sex difference was significant (P less than .01) while the difference in Pb-B between winter and summer was essentially insignificant. Both drinking and smoking habits were associated with a dose dependent increase in blood lead levels, especially in males; the increment was additive when the examinee was a drinker-smoker. The geographical difference in blood lead levels remained inconclusive. PMID- 4026389 TI - Prevalence of hypertension among cadmium-exposed workers. AB - In a retrospective study of 311 male workers in an alkaline battery factory, the relationship between exposure to cadmium oxide and hypertension has been investigated. Blood pressure measurements, taken by the same physician, were available for a 30-yr period. When age-matched groups of hypertensive and normotensive workers were compared, employment time was significantly longer (P = .0109) in the hypertensive group. This indicates a possible relationship between exposure to cadmium oxide and the development of hypertension. PMID- 4026390 TI - Placental protein 5 (PP5) inhibits thrombin-induced coagulation of fibrinogen. AB - The effect of Placental Protein 5 (PP5) on thrombin-induced coagulation of diluted fibrinogen is described. In contrast to previous reports which failed to demonstrate antithrombin-like activity for PP5 on synthetic substrates, we show in this study that PP5 inhibits thrombin activity in a dose-dependent manner. PP5 acts thus in a very similar way to antithrombin III (ATIII). Although PP5 binds to heparin, it does not show any heparin-cofactor activity. Whereas catalytic amounts of heparin accelerate greatly the inhibitory effect of ATIII, no accelerating effect of heparin on PP5 could be observed under the same conditions. In spite of its anti-thrombin activity, PP5 cannot be considered as a pregnancy-analogue of ATIII, as it lacks the heparin-cofactor activity. PMID- 4026391 TI - The prevalence of ureaplasma, mycoplasma and antibodies against chlamydia group antigen in gynecological outpatients. AB - 177 women with an average age of 30 years were investigated for ureaplasma, mycoplasma and for antibodies against the chlamydia group antigen. Specimen of endocervical mucus and catheter specimens of urine were cultured and the ELISA ("enzyme-linked immunosorbent assay") technique applied. In addition the purity class (I to III) of gram-stained vaginal smears was determined. Ureaplasma were isolated from 45.8 and 26.0%, mycoplasma from 9.0 and 7.9% of cervical and urine specimens respectively. The patients were divided into 5 clinical groups. Patients in the first three groups (I-III, inflammatory disorders, bleeding anomalies, benign and malignant neoplasms of the genital tract) showed a significantly (p less than or equal to 0.05) higher colony count of ureaplasma in their urine than patients in the other two groups (IV and V, who had attended the hospital for reproductive problems or for routine examination). There was a clear correlation between the isolation rates of ureaplasma and mycoplasma and the purity classes of the vaginal smears. The rate of isolation increased progressively with class II and III smears. Antibodies against the chlamydia group antigen were detected in about 40% of all sera tested. A very high titer of antibodies reflecting a recent chlamydial infection was found in 11% of the sera tested. PMID- 4026392 TI - [Cranial blind ureter: national review]. PMID- 4026393 TI - [In situ carcinoma of the bladder]. PMID- 4026394 TI - [Early detection of bone metastases in carcinoma of the prostate using the gamma camera]. PMID- 4026395 TI - [Surgery of renal carcinoma: transperitoneal subcostal access]. PMID- 4026396 TI - [Genitourinary complications in oncology]. PMID- 4026397 TI - [Primary hyperparathyroidism and renal lithiasis. Effect of delay in diagnosis on the morbidity]. PMID- 4026398 TI - [Our experience in the surgical treatment of staghorn lithiasis]. PMID- 4026399 TI - [Anesthetic block of the spermatic cord in 150 consecutive scrotal surgeries. An incentive to ambulatory surgery]. PMID- 4026400 TI - [Ureteral triplication: report of a new case]. PMID- 4026401 TI - [Bilateral renal adenocarcinoma in Von Hippel-Lindau syndrome: apropos of a case]. PMID- 4026402 TI - [Lithiasis in a blind ureterocele]. PMID- 4026403 TI - [Effects of pinealectomy on the ventral prostatic lobe and the seminal vesicles/coagulating glands of albino rats (I)]. PMID- 4026404 TI - Disease activity indexes in rheumatoid arthritis; a prospective, comparative study with thermography. AB - There are many difficulties associated with the assessment of disease activity in rheumatoid arthritis. Infrared thermography has been used to quantify joint inflammation. The heat distribution index (HDI) is reproducible, sensitive, quantifiable, and not subject to circadian variation or interobserver error. In this study the HDIs for both elbows, wrists, knees, and ankles were summated and compared with other parameters of disease activity. There were 167 sets of observations in 20 patients with classical, seropositive, rheumatoid arthritis followed up over 12 months. There was a significant correlation (p less than 0.001) for thermography with the Ritchie articular index, Mallya score, grip strength, morning stiffness, erythrocyte sedimentation rate, and pain score. Significant correlations (p less than 0.05) for thermography with these parameters were found in individual patients. The summated HDI is a suitable, objective method for the assessment of response to therapy in patients with rheumatoid arthritis. PMID- 4026405 TI - Enhanced prostanoid release from monocytes of patients with rheumatoid arthritis and active systemic lupus erythematosus. AB - In patients with rheumatoid arthritis high levels of prostaglandin E1 have been found in the joint fluid, and its increased production by adherent synovial cells and macrophages clearly supports the notion that this arachidonic acid metabolite is involved in the pathology of the disease. Besides its known inflammatory qualities and the suppressive effects on various lymphocyte functions prostaglandin E2 has proved to be an essential cofactor in the secretion of the lymphokine osteoclast activating factor. In this study we have discovered an enhanced release of prostaglandin E1 and thromboxane B2 from a subpopulation of blood monocytes from patients with rheumatoid arthritis and active systemic lupus erythematosus. No correlation between prostanoid release from monocytes and inflammatory activity of the disease was found. However, even monocytes from patients with early stage or mild inflammatory activity displayed a 'stimulated' arachidonic acid metabolism. In contrast only patients with active systemic lupus erythematosus showed in this respect comparable secretory activity or monocytes. Our findings may point to a possible pathogenic role of prostanoids in rheumatoid arthritis, which may also have some implication for the early diagnosis of this disease and for its differentiation from other chronic inflammatory rheumatic conditions. PMID- 4026406 TI - Lung involvement in Sjogren's syndrome: a comparison between patients with primary and with secondary syndrome. AB - Lung function was assessed in 20 patients with primary Sjogren's syndrome (SS) and in a group of patients with SS associated with a variety of connective tissue diseases. Signs of small airway disease and of altered diffusion capacity, together with chest x-ray features of mild interstitial involvement, were the most common findings in primary SS. On the whole, lung involvement was more frequent and severe in patients with the secondary form of the syndrome. In both primary and secondary SS lung function changes did not correlate with the other clinical and serological parameters, except for a more severe impairment of diffusion capacity in patients with Raynaud's phenomenon. PMID- 4026407 TI - Reference values for metacarpophalangeal joint stiffness in normals. AB - A new form of microprocessor-controlled arthrograph is described which measures stiffness parameters of the metacarpophalangeal joints of the index, middle, and ring fingers of both hands. The apparatus is simple and quick to use and gives reproducible results. The arthrograph is used to determine the reference limits for stiffness at the middle finger of the right hand in 128 normal subjects. It is found that incorporating information on the subject's finger circumference allows a much improved precision to be achieved, but the precision is not further enhanced by including details of age and sex. PMID- 4026408 TI - Carrageenin-induced arthritis. VI. Alterations in amino acid transport by articular cartilage in acute inflammatory arthritis. AB - The mechanism of transport of alanine and aminoisobutyric acid into chondrocytes in rabbit articular cartilage was shown to be mediated by transport systems similar to that described for other eukaryotic cells namely the A, ASC, and L systems. Three days after the initiation of an acute inflammatory arthritis by the intra-articular injection of carrageenin into one knee joint the rate of transport of both these amino acids was decreased. Although all three transport systems were depressed, it appeared that the A and ASC systems were partially susceptible to damage by the induced inflammation. The rate of amino acid transport by the affected cartilage had recovered by 28 days after carrageenin treatment. This depression in amino acid transport is discussed in relation to a decrease in general metabolic processes in chondrocytes as a consequence of inflammation. PMID- 4026409 TI - Effect of blood on the activity and persistence of antigen induced inflammation in the rat air pouch. AB - The hypothesis that haem iron derived from synovial microbleeding has a proinflammatory effect on the synovial membrane was tested by adding autologous whole blood and fractions derived from it to a naturally remitting rat air pouch model of allergic inflammation. The induction of such a subcutaneous air pouch produces a cavity lined by mesenchymal cells comparable to the synovial membrane. Autologous whole blood was found to prolong a low grade inflammatory state, this effect being attributable to a red cell component, most probably haem iron. Whole blood in the absence of an inflammatory stimulus does not have this effect, indicating that the mechanism is one of prolonging or promoting existing allergic inflammation, rather than inducing an inflammatory response. PMID- 4026410 TI - Calcinosis of joints and periarticular tissues associated with vitamin D intoxication. AB - We describe a patient with rheumatoid arthritis and widespread joint and periarticular calcinosis related to self-medication with vitamin D, which was aggravated by oral phosphate therapy prescribed for her hypercalcaemia. Hydroxyapatite was shown in the synovial fluid from affected joints. The role played by tissue injury in the pathogenesis of soft tissue calcification is discussed. PMID- 4026411 TI - IgG monoclonal gammopathy in four patients with polymyalgia rheumatica. PMID- 4026412 TI - Piroxicam induced lithium toxicity. PMID- 4026413 TI - Subnormal sensitivity of neutrophils to complement split product C5a in rheumatoid arthritis: relation to complement catabolism and disease extent. AB - The capacity of circulating neutrophils for activation by complement was studied in outpatients with classical or definite rheumatoid arthritis during treatment with dextropropoxyphene only. Analysis of dose-response in the Boyden chamber assay of chemotaxis showed that sensitivity to the potent, complement derived anaphylatoxin, C5a, was markedly decreased, especially in those patients with few joints involved. In contrast, peak response to C5a was within the normal range. Increased complement 3c split products in plasma of the patients suggested involvement of complement cascade reactions. Subnormal sensitivity of neutrophils to phlogistic mediators released by complement may tend to limit their recruitment and potentially tissue destroying secretion locally in rheumatoid arthritis. PMID- 4026414 TI - Tissue typing in brucellosis. AB - The index case in this report was clinically, epidemiologically, and serologically proved to be suffering from acute brucellosis acquired in Britain and complicated by acute intractable reactive arthritis. HLA tissue typing was A1, A2, B7, and B27. As there is no information available about HLA typing in brucellosis in Britain, we examined further cases of human brucellosis retrospectively. Three further patients possessing B27 antigen were identified, only one of whom had had reactive arthritis. Eight of the 12 cases studied also carried A2, which is thus shown not to be protective against the development of brucellosis as had been suggested previously. PMID- 4026415 TI - Systemic response to local urate crystal induced inflammation in man: a possible model to study the acute phase response. AB - The production of a systemic inflammatory response to intradermal monosodium urate crystal injection is described. A transient, self-limiting local response is associated with a systemic response detectable by a rise in the white cell count and serum amyloid A protein. The white cell change parallels the evolution of the local response, whereas the serum amyloid A response lags behind the local lesion, peaking after the local lesion is resolving. Intradermal monosodium urate injection is proposed as a possible inflammatory stimulus to explore the acute phase protein response in different disease states. PMID- 4026417 TI - Remission of arthritis and radiological improvement after combination therapy for non-Hodgkin's lymphoma in a patient with rheumatoid arthritis undergoing treatment with D-penicillamine. AB - A patient receiving d-penicillamine for rheumatoid arthritis developed a lymphoma, therapy for which resulted not only in haematological resolution but marked remission of rheumatoid disease activity, including radiological improvement. PMID- 4026416 TI - Multiple microcrystal deposition within a family. AB - A family is described in which four members in three generations showed evidence of crystal deposition disease: two developed calcium pyrophosphate dihydrate (CPPD) crystal deposition, one calcific periarthritis, and one mixed crystal deposition disease (gout + chondrocalcinosis). This previously undescribed observation supports a possible role for nonspecific heritable connective tissue factors in predisposing to crystal deposition. PMID- 4026418 TI - An unusual case of Reiter's disease. AB - A 72-year-old man was admitted to hospital after a syncopal attack. Investigations showed anaemia and adenocarcinoma of the colon. After tumour resection with end to end anastomosis he had a urinary catheter in situ for two days, but otherwise his recovery was unremarkable, until 13 weeks after operation when he developed classical Reiter's disease. Investigations did not reveal any known trigger factor but it is postulated that the process may have been initiated by urinary catheterisation or bowel surgery. PMID- 4026419 TI - Cushing's syndrome with suppression of the hypothalamic-pituitary-adrenal axis after intra-articular steroid injections. AB - A case of Cushing's syndrome after long term intra-articular corticosteroid injections is described. Prolonged suppression of the hypothalamic-pituitary adrenal axis occurred as assessed by an insulin tolerance test 11 weeks after the last intra-articular injection. Replacement steroid therapy was required. PMID- 4026421 TI - Geode: crystal-containing cavity, lymph space, or pseudocyst? PMID- 4026420 TI - Sequential studies on synovial lymphocyte stimulation by rubella antigen, and rubella virus isolation in an adult with persistent arthritis. AB - The response of synovial lymphocytes from a 65-year-old lady with persistent polyarthritis, to rubella antigen and a number of other microbial agents was studied over a period of 11 months by [3H]thymidine incorporation. The results were correlated with the ability to isolate rubella virus from both peripheral blood and synovial fluid during the same period. The patient showed initially a maximal stimulation index to rubella antigen assayed on five occasions over a five-month period. Rubella virus was detected in both peripheral blood and synovial fluid samples on three occasions during this period. Five months later the lymphoproliferative response of her synovial lymphocytes to rubella antigen had dropped to low levels, and virus could no longer be isolated from synovial exudates. At this time the patient's arthritis had become much less active, indicating that a good correlation existed between the presence of rubella virus, local lymphocyte sensitisation, and the inflammatory reaction. PMID- 4026422 TI - Lyme disease in Italy: first reported case. PMID- 4026423 TI - A rheumatological dilemma. PMID- 4026424 TI - Intravenous iron in the treatment of rheumatoid arthritis. PMID- 4026425 TI - Detection of anti-dsDNA as a diagnostic tool. PMID- 4026426 TI - Secondary surgery of the flexor pollicis longus tendon. A comparative study of forty-three cases. AB - The authors report their experience in dealing with 43 cases of secondary surgery on the flexor pollicis longus tendon between 1970 and 1982. After an anatomical and biomechanical survey, the results of the different techniques used are analyzed: tenolysis (12 cases). tenodesis (one case), one- (3 cases) or two-stage (4 cases) grafts, flexor digitorum superficialis (FDS) transfer (11 cases) and secondary sutures (12 cases). The overall outcome was very disappointing, with 50 per cent poor results. Compared with the other techniques, secondary suture fared best, and it can be combined, if need be, with tendon lengthening at the wrist and metacarpo-phalangeal pulley reconstruction. Considering these results, therapeutic indications are proposed. The functional requirements of the patient may lead to prefer simple interphalangeal fusion to any dynamic method. PMID- 4026427 TI - Microsurgical relations of the roots of the brachial plexus. Practical applications. AB - The brachial plexus roots were studied in 20 cadavers under magnification from their origin (division of the corresponding cervical spinal nerves) until their ending (origin of the corresponding trunks). Regional vascular injections were performed in 10 cases using colored latex. The means of fixation of each plexus root to the spine, as well as the collateral branches, the anastomoses and the vascular connections are described. The authors conclude by the description of a microsurgical posterior approach of C5-C6 and C7 up to their origin, with clinical applications. PMID- 4026428 TI - Proposal of a new classification for established Volkmann's contracture. AB - The multiple contributory aspects of the claw deformity seen in 115 cases of established Volkmann's contracture has been analyzed. This has given rise to a clinically oriented 5-Stage classification. Clinical and electrical motor nerve deficits in the median, ulnar and radial distributions have shown considerable variability between patients. The individual pattern of nerve damage has been outlined. The measurement of passive extension deficits (PED) illustrates the degree of extrinsic muscle contracture. The PED is increased proportionally to nerve damage. Secondary stigmata of chronic ischemia (ie chronic changes, sensory deficits,stiff joints, web-space and intrinsic contractures) are increased proportionally to muscle and motor nerve damage. Staging in these five groups has permitted the establishment of rapid diagnosis, severity of injury, prognostic evaluation and management modalities according to stage. PMID- 4026429 TI - Radiological study of the mobility of the scapho-lunate joint. AB - Based on the study of 126 wrists, it was possible to determine that 36 degrees of normal laxity exists in the scapholunate complex. This was documented by the comparative measurements of the total range of movement of these two bones on sagittal plane X-rays. No difference between the dominant and non dominant hands was observed. Cadaveric experimental studies as well as the records of 13 pathological wrists showed that scapholunate laxity was greater when the scapholunate ligament was involved. Measuring scapholunate movements on sagittal motion roentgenographic views can detect pathological laxity between these two bones, considering that 15 degrees is the minimal difference permitted. PMID- 4026430 TI - The medial metacarpotrapezial collateral ligament: importance of the fourth fascicle. AB - The metacarporetinacular fascicle, the fourth fascicle of the medial collateral metacarpotrapezial ligament, was examined in 25 anatomic specimens. It contributes to stability of the ligament and plays an important role in the pronosupination of the thumb. This role becomes determinate when the geometry of the articular surfaces is disturbed. PMID- 4026431 TI - Biometrical study of flexion of the long fingers joints in prehension. AB - The angles of flexion of the three digital joints were measured in 112 hands while grasping test cylinders the diameter of which ranged from 8 to 90 mm. Based on the average of several measurements, the angles of overall and joint-by-joint flexion were determined for each cylinder size. Studied finger by finger, it was shown the each digit has its individual pattern of flexion, the angles of flexion of each joint being different for each finger. Flexion is prevalent in the proximal interphalangeal joint of the index while it is prevalent in the metacarpophalangeal joint of the little finger. When the standard deviation values were calculated, they showed that the individual variations were relatively small in cylindrical grasps. This is the opposite of what was observed in two of the pinches between the thumb and the other fingers. In these cases, the values of the angles of flexion were remarkably dispersed according to the individuals, especially in the proximal interphalangeal joint. PMID- 4026432 TI - [Tenosynovitis of the hand due to Mycobacterium marinum. Apropos of a case]. AB - The authors report one case of Mycobacterium marinum of the deep structures of the hand and review the literature on the subject. The symptoms are not specific: biopsy and culture are essential for diagnosis. As chemotherapy does not seem to be of help, wide surgical incision is the appropriate treatment. PMID- 4026433 TI - [Anatomical study of the vascularization of the flag flap. Apropos of its use in loss of substance from the palmar face of the proximal phalanx]. AB - The flag flap, elevated from the dorsal aspect of the proximal phalanx, may be employed as a one-stage procedure to cover a loss of soft tissue on the volar aspect of the adjacent finger, the staff of the flap running over an oblique web space incision. PMID- 4026434 TI - [Fractures of the long metacarpals. Long-term results]. AB - Sixty-seven of long metacarpal fractures have been followed for more than one year. Digital mobility and strength of grasp of the traumatized hand were measured and then compared with the healthy hand, the result being modified, according to the patient's own appreciation. This clinical examination enabled a medium and long term assessment of functional results. Control radiograms helped us draw up a chart of the various types of fractures, their topographical distribution and eventual anatomical modifications according to displacement. When comparing clinical and radiographic results, a correlation is--or is not- possible between the functional deficit and the degree of deformation of the metacarpals. Clinical results also depend on other factors which may influence the final result. PMID- 4026435 TI - Technique and indications of the forearm flap in hand surgery. A report of thirty three cases. AB - The Chinese forearm flap is vascularized by the radial artery and may be used as an island or a free flap. Used as an island flap, the pitfalls of the microsurgical procedures required for a free flap, may be avoided. Vascular anastomosis is easily performed owing to the large diameter of the vessel. The possibility of using it as a composite flap with fascia, tendons, muscle, bone or nerve makes this flap a "must" in reconstructive surgery of the hand. A series of 33 cases was reviewed in an attempt to summarize their indications and contraindications respectively. PMID- 4026436 TI - Thumb reconstruction pollicisation or toe-to-hand transfers. A comparative study of functional results. AB - A statistical study of thumb reconstruction after traumatic amputation, based on the records of 33 pollicisations and 21 microsurgical toe-to-hand transfers was made. A precise method of evaluation of results is presented. The types of lesions are divided into 4 groups; 1: amputation of the thumb without injuries of the other fingers; 2: amputation of the thumb associated with amputations or mutilation of other fingers; 3: metacarpal hand; 4: amputation of the thumb distal to the metacarpophalangeal joint. The aim of this study was to determine the respective indications of the two methods. It may be concluded that: in group 1, the results of pollicisation and of toe-to-hand transfers are similar. The former is superior as far as the discriminative sensory and fine motor results are concerned, while toe transfer reestablishes better strength. In group 2, the more the other fingers are mutilated, the more toe transfers should be preferred to pollicisation which weakens the performance of the long fingers, especially when they are injured. In group 3 (metacarpal hand), the transfer of one or more toes is a revolution. It is the only technique capable of returning function and, if technique is correct, a cosmetically satisfactory aspect as well. In distal amputations of the thumb (group 4), the only indications for pollicisation are cases of a proximally injured finger with a healthy distal segment, transferable on healthy pedicles, which is relatively rare. Partial toe-to-hand transfers, is a new solution to this challenge. PMID- 4026437 TI - A comparison of the pyrimethamine and cycloguanil sensitivities of the pre erythrocytic and erythrocytic stages of drug-sensitive and -resistant strains of Plasmodium yoelii. AB - The cycloguanil and pyrimethamine sensitivities of the pre-erythrocytic and erythrocytic stages of a drug-sensitive and drug-resistant strain of Plasmodium yoelii have been compared. With both compounds, and in both parasite strains, the pre-erythrocytic stages were more sensitive to inhibition than were the erythrocytic stages. In the resistant strain the increase in the level of drug tolerance in the erythrocytic stages was paralleled by a corresponding loss of sensitivity in the pre-erythrocytic stages. PMID- 4026438 TI - An experimental vaccine against American dermal leishmaniasis: experience in the State of Espirito Santo, Brazil. AB - A vaccine prepared from killed and sonicated promastigotes of five Brazilian strains of Leishmania was used during an epidemic of American dermal leishmaniasis that occurred in Viana county, State of Espirito Santo, Brazil. Initially, all of the participants in the vaccination programme had negative reactions to Montenegro antigen. Forty days after the last dose of vaccine had been given, 87.6% of the 216 vaccinated individuals had become Montenegro positive whereas the 266 unvaccinated persons remained Montenegro-negative. The study area had an unstable population and details are given about the human population changes that occurred during the two-year study period. Taking into account population movements, 1.5% of those vaccinated and 6.4% of the unvaccinated group developed dermal leishmanial lesions by the end of the first year. At the end of the second year, 1.7% of those vaccinated and 8.9% of the unvaccinated group had become infected. The difference in infection rates of the two groups is statistically significant at both the end of the first and second years of observation. Diagnosis of the disease(s) was based on the clinical appearance of lesions combined with parasitological and/or immunological evidence and subsequent responses to treatment. The experience gained in Viana also provided information about the storage and administration of the experimental vaccine which have been used in mounting a randomized clinical trial. PMID- 4026439 TI - Liver abscess in Dubai. An analysis of 29 cases and an assessment of the value of CAT scan. AB - The clinical features and management of 29 consecutive cases of liver abscess admitted to the Medical Division at the Rashid Hospital, Dubai, between February 1979 and March 1982 are reviewed and the value of CAT scan in the diagnosis and management is assessed. PMID- 4026440 TI - Prevalence and distribution of schistosomiasis in Zimbabwe. AB - Surveys for schistosomiasis of 14 619 eight- to ten-year-old children from 157 schools in Zimbabwe are reported. Zimbabwe is divided into three regions on the basis of differing prevalences of Schistosoma haematobium, with mean prevalence levels in each zone of 63.2, 37.1 and 14.3%. Two regions were identified for S. mansoni, with mean prevalence levels of 15.2 and 1.5%. In most regions Commercial Farming areas were shown to have higher levels of infection than Subsistence Farming areas. Females showed a significantly lower prevalence of infection with S. haematobium than males in all areas. Age prevalence surveys in support of the major survey showed the seven- to 20-year-old age group to contain 91.5% of the heavy infections with S. haematobium and 83.7% of the heavy infections with S. mansoni. The availability of surface water is recognized as the major factor governing the distribution and prevalence of schistosomiasis. Control of schistosomiasis is briefly discussed. PMID- 4026441 TI - Severe strongyloidiasis presenting as occult gastro-intestinal tract malignancy. AB - A 38-year-old man presented with severe loss of weight, diarrhoea alternating with constipation and blood in the stool. Clinically, colonic malignancy was suspected, but this was not confirmed. Fresh stool contained numerous larvae of Strongyloides stercoralis. The patient responded promptly to levamisole, with cessation of symptoms and rapid weight gain. PMID- 4026442 TI - Venom antibody levels in a patient bitten by a young puff adder (Bitis arietans) during a world record attempt. AB - Following a bite on the hand by a young puff adder (Bitis arietans), the 21-year old male victim was admitted to hospital suffering from symptoms of mild envenoming comprising swelling to the elbow and painful axillary nodes. The patient was not treated with antivenom. One day after the bite, B. arietans venom was detected in small amounts in the blood; none was detected subsequently. Venom antibody was detected by ELISA on the ninth day after the bite, rising to a peak after three weeks. After a further 11 days at the same level, antibody levels gradually fell but were still significantly high 81 days after the bite, when no further samples were taken. It appears unlikely in this case that a previous bite two and a half years earlier by a different species of snake contributed significantly to the development and intensity of the antibody response. PMID- 4026443 TI - Extrachromosomal inheritance of susceptibility to trypanosome infection in tsetse flies. I. Selection of susceptible and refractory lines of Glossina morsitans morsitans. AB - Differences in susceptibility to infection with Trypanosoma congolense between F1 families of Glossina morsitans morsitans indicated that susceptibility is maternally inherited in this species of tsetse fly. Twelve F1 families, six selected for susceptibility and six selected for refractoriness to infection, have been bred for up to 13 generations. The reciprocal differences demonstrated in the F1 generation persisted in these selected families over many generations, indicating that susceptibility/refractoriness to T. congolense infection is extrachromosomally inherited in G. m. morsitans. Repeated 'backcrossing' to males of the opposite strain showed that infection rates within families were independent of the contribution of the male parent. Susceptible families had a mean midgut infection rate of 76.9% and a mature (hypopharyngeal) infection rate of 47.9%. In the refractory families 88.9% of the flies failed to develop an infection, 11.1% had midgut infections and only 6.3% developed mature infections. Levels of midgut infection remained remarkably constant within families over generations, whether refractory or susceptible, while maturation rates varied between generations and between sexes. Males matured a significantly greater proportion of midgut infections than females in the susceptible families. It is suggested that the inheritance of susceptibility/refractoriness relates primarily to the establishment of midgut infections in G. m. morsitans, and that maturation of midgut infections is dependent upon environmental factors such as diet, and differences between sexes probably reflecting differences in rates of bloodmeal digestion.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4026444 TI - Genetic relationships among certain species of the Aedes (Stegomyia) scutellaris group (Diptera: Culicidae). AB - Genetic affinities between species of the Aedes (Stegomyia) scutellaris group were determined through experimental hybridization. In this investigation Aedes hebrideus and Ae. scutellaris katherinensis were reciprocally crossed with Ae. polynesiensis, Ae. pseudoscutellaris, Ae. kesseli, Ae. malayensis, Ae. alcasidi and Ae. albopictus. Data on insemination and egg hatch rates were recorded in the reciprocal crosses. Of these, Ae. hebrideus and Ae alcasidi, Ae. hebrideus and Ae. s. katherinensis, Ae. malayensis and Ae. hebrideus, and Ae. malayensis and Ae. s. katherinensis, were unidirectionally compatible using female parent of former species of the two. The reciprocal crosses of these laid infertile eggs. Aedes s. katherinensis and Ae. alcasidi were bidirectionally compatible. All other interspecific crosses were incompatible producing infertile eggs. In the compatible crosses, i.e. where the viable hybrids were obtained, F2 and hybrid fertilities were determined. Species hybrids obtained by crossing Ae. malayensis females and Ae. s. katherinensis males yielded lower fertility in F2 and differential fertility when backcrossed. Species hybrids obtained by crossing Ae. s. katherinensis females and Ae. alcasidi males resulted in lower fertility in F2 and also when backcrossed to Ae. s. katherinensis females. All other species hybrids were fertile. Based on the data obtained, Ae. hebrideus, Ae. s. katherinensis, Ae. malayensis and Ae. alcasidi formed a sub-grouping which showed remote genetic affinities individually or as a group with rest of the species investigated. PMID- 4026445 TI - Leishmaniasis in the south-east of Spain: preliminary results of a serological and parasitological study in dogs. PMID- 4026446 TI - Reoperation in congenital aortic stenosis. AB - Over a 22-year period, 81 patients underwent initial operations for critical aortic stenosis at our institution. Their ages ranged from 3 days to 20 years (mean, 7.3 +/- 5.9 years). Fourteen (17%) were infants less than 1 year old. Three children died perioperatively (3.7%). We have followed the survivors and 3 children who underwent initial operations elsewhere for a mean of 9.0 +/- 6.8 years (range, 2 to 23 years). To the present, 27 patients have undergone one reoperation (24 of our initial survivors) at a mean interval of 7.3 years, with 2 perioperative deaths. Ten of these patients have required a second reoperation at a mean interval of 3.7 years, with 2 deaths perioperatively. There were 3 late cardiac deaths after the initial procedure and 1 after a third operation. Actuarial reoperation-free survival is 56.7% at 10 years. While overall survival is 88.6% at 10 years, we find a significantly poorer survival among those patients with valvular stenosis compared with those with subvalvular lesions (p = 0.03). We believe that for children with all levels of aortic stenosis, good functional results and survival can best be obtained by follow-up, recatheterization, and reoperation. PMID- 4026447 TI - Avoidance of transverse midventricular disruption following mitral valve replacement. AB - From 1974 through 1977 when our hospital mortality for aortic valve replacement and myocardial revascularization was 3.5% and 1.1%, respectively, hospital mortality for mitral valve replacement (MVR) was 8.3% (13/156)--as high as 14.9% in 1976. Transverse midventricular disruption (TMD) was present in 7 of 10 patients on whom an autopsy was done and was clinically diagnosed in 3 others without postmortem examination. Transverse midventricular disruption presented as refractory myocardial failure immediately on termination of bypass or later (1 to 5 days) after an initial period of good hemodynamics. It appeared to result when volume loading or afterload pressure was returned to the untethered ventricle after MVR performed with potassium-induced, cold cardioplegia and ischemic arrest. Operative techniques were modified to preserve a portion of the mitral suspensory mechanism, to extend the reperfusion interval following cardioplegia and ischemic arrest, and to control strictly ventricular volume and pressure loading following bypass. By utilizing these methods, TMD was avoided from 1978 through 1982, and hospital mortality for MVR was 3.7% (9/241). The improved hospital mortality and avoidance of TMD did not result from patient selection. Allowing adequate time for recovery of the myocardium after cardioplegia plus ischemic arrest prior to ventricular loading, preservation of mitral suspensory function, and strict control of preload and afterload pressures have been effective in lowering hospital mortality for MVR and have eliminated TMD in a 5 year period. PMID- 4026448 TI - Patency rate of bifurcated aortic grafts: comparative analysis of woven versus knitted prostheses in the same patient. AB - To investigate the difference in patency rate between woven and knitted aortofemoral or aortoiliac prosthetic grafts, a special vascular prosthesis was manufactured with one limb of the graft knitted and the other, woven. The prosthesis was implanted in 143 consecutive patients with occlusive aortoiliac arteriosclerotic disease or aneurysms. Detailed statistical analysis failed to reveal any difference in the patency rate between the woven and knitted limbs of the grafts during an observation period ranging from one month to two years. PMID- 4026450 TI - The modern use of thoracoplasty. AB - Thoracoplasty is a time-honored but, at present, rarely indicated procedure for reducing thoracic cavity volume. This study reviews a series of 30 patients treated with thoracoplasty over a 14-year period (1970 through 1983). Indications were to close a persistent pleural space in 28 patients and to tailor the thoracic cavity to accept diminished lung volume concomitant with a pulmonary resection in 2 patients. Persistent pleural space, often associated with a bronchopleural fistula (24 patients), occurred after operation in 19 patients: following pulmonary resection in 17 patients, resection of mesothelioma in 1 patient, and following decortication without resection in 1. In the remaining 9 patients with a persistent pleural space, problems developed from primary lung destruction due to tuberculosis (4 patients), postpneumonic empyema (1 patient), or as late infection of a residual pleural space many years after therapeutic pneumothorax and collapse therapy for tuberculosis (4 patients). The overall success rate of thoracoplasty in eliminating intrathoracic space problems was 73%. There were 3 deaths (10%) and 5 failures to heal, representing a 33% failure in the first half of the series (to 1976) and a 17% failure rate thereafter (1 death and 1 nonhealing patient). The primary underlying disease was tuberculosis in 23 patients, 8 of whom had concomitant aspergilloma and 1, atypical tuberculosis. The failures were analyzed and reviewed to clarify the principles for the successful use of thoracoplasty. It is concluded that thoracoplasty is a rarely required salvage-type procedure applicable to moderately debilitated patients in whom it is considered desirable to eliminate open drainage.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4026449 TI - Relation of calcification to torn leaflets of spontaneously degenerated porcine bioprosthetic valves. AB - The gross appearance of 54 spontaneously degenerated porcine bioprosthetic valves was evaluated to determine the relation of calcium deposition to cusp disruption. Tears or perforations were shown in 89% (48) of the degenerated valves. The most common site of tears or perforations was near the commissural attachment (60% of all tears). Grossly visible deposits of calcium salts that ruptured to the surface of the cusps or caused changes in the topography were observed in 70% (38) of the 54 valves. Calcification was adjacent to tears or perforations in 56% (27) of the 48 valves with torn cusps. Among the valves that showed calcification, the deposits of calcium salts were adjacent to tears or perforations in 71% (27 of 38). The location of deposits of calcium did not relate to the age or sex of the patient or to the position of the valve, but valves with calcium were inserted longer than valves with no calcium (87 +/- 4 versus 58 +/- 7 months; p less than 0.001). The outflow surfaces showed more calcification than the inflow surfaces, irrespective of whether the valves were in the aortic or mitral position. Among the 38 valves with calcification, 92% (35) showed calcification at the commissural attachments, 53% (20) showed calcification in the body of 1 or more cusps, 11% (4) near the base, and 8% (3) near the free edge. In conclusion, most patients with spontaneous porcine valve degeneration showed calcification. The calcification was associated with tears or perforations of the cusps in 50% of all degenerated valves, in 56% of valves with torn cusps, and in 71% of valves that showed gross calcification. PMID- 4026451 TI - Emergency thoracotomy: a four-year review. AB - The case records of 200 patients who had emergency thoracotomy for penetrating trauma were reviewed. The mortality was 47% (93/200) for the entire series, 27% (21/79) for stab wounds and 60% (72/121) for gunshot wounds. Of 55 patients who underwent thoracotomy in the emergency department, 8 (15%) survived. Twelve patients "dead" at the scene could not be resuscitated. Nineteen patients sustained cardiac arrest in the ambulance, 3 (16%) of whom survived. Of 19 who had cardiac arrest in the emergency department, 5 (26%) survived. Of 38 patients who had cardiac arrest in the ambulance or emergency department, 14 with stab wounds had a 43% survival and 24 with gunshot wounds had a survival of only 8%. Patients who underwent thoracotomy in the operating room (OR) had a higher survival, 68% (99/145). For those with thoracic, extremity, or neck injuries, survival was 81% (93/115). For those who had an OR thoracotomy for aortic cross clamping because of abdominal injuries, survival was only 17% (5/30). Early thoracotomy has a place in the management of patients who have cardiac arrest in the ambulance or emergency department because of penetrating chest, neck, or extremity injuries, especially if caused by stab wounds. Cross-clamping of the thoracic aorta for massive abdominal bleeding should be applied selectively. PMID- 4026452 TI - Total cavopulmonary shunt with replacement of common atrioventricular valve for an infant with single atrium and single ventricle. AB - A 22-month-old male infant with single atrium, single ventricle, regurgitant common atrioventricular valve, pulmonary atresia, patent ductus arteriosus, and inferior vena cava defect with azygos connection was treated successfully with total cavopulmonary shunt and replacement of the common atrioventricular valve. The indications for total cavopulmonary shunt in the management of univentricular heart with azygos continuity are discussed. PMID- 4026453 TI - Posttraumatic thoracic aortic aneurysm associated with a diaphragmatic hernia. AB - The case of a patient with a chronic, posttraumatic descending thoracic aortic aneurysm and a large diaphragmatic hernia is presented. We repaired the diaphragm with Prolene mesh and externally grafted the aneurysm. To our knowledge, simultaneous repair of these two chronic injuries has not been reported. The merits of external grafting of aortic aneurysms are discussed. PMID- 4026454 TI - Ultrasonic aspiration in coronary artery surgery. AB - With the aid of an ultrasonically powered aspiration device, the coronary artery to undergo distal anastomosis during aortocoronary bypass grafting can be exposed in the beating heart prior to institution of cardiopulmonary bypass and systemic administration of heparin. The thick adipose tissue and bridging muscles of the superficial layer are removed with almost no bleeding, leaving the vascular elements intact. The optimal site for anastomosis of the coronary artery is readily exposed and confirmed, and aortic cross-clamp time is minimized. PMID- 4026455 TI - Intracavitary coronary arteries. PMID- 4026456 TI - Mechanism of flavoxate antispasmodic activity comparative in vitro studies. AB - In order to clarify the pharmacological activity of flavoxate, its effect on the tone and spontaneous activity of the guinea-pig isolated ureter and of the muscle strip from rat urinary bladder were studied. Flavoxate, as well as papaverine, reduced all three parameters considered on the guinea-pig isolated ureter, namely: peristaltic motility, endoluminal pressure and longitudinal muscle contractility. In the same test, verapamil (a calcium antagonist), emepronium and atropine (both anticholinergic drugs) were used for comparison. Using strips of rat urinary bladder depolarized by KCl, flavoxate, papaverine and verapamil displayed a relaxant activity, while anticholinergic compounds such as atropine, hyoscine and emepronium failed to relax this tissue. In another series of experiments the effects of flavoxate and anticholinergic drugs on the contraction elicited by vagal electrical stimulation of the guinea-pig isolated stomach in toto were assayed. The results obtained suggest that the action of flavoxate is due to direct smooth muscle relaxation and does not involve anticholinergic activity. PMID- 4026457 TI - Interactions of 5-hydroxytryptamine and tricyclic antidepressants in the rat stomach strip and the guinea-pig ileum. AB - The interactions of the tricyclic antidepressants, amitriptyline and desipramine with 5-hydroxytryptamine (5-HT) were studied in the guinea-pig ileum and in the rat stomach strip. The tricyclics blocked the contractile response of the guinea pig ileum and severely depressed the maximum [amitriptyline greater than desipramine (DMI)], however, they potentiated (DMI greater than amitriptyline) 5 HT-induced contractions of the RSS. The potentiation induced with DMI seems to be a combination of uptake inhibition and some post-receptor sensitization whilst amitriptyline-induced potentiation may be due to the former. Higher concentrations of the tricyclics contract the RSS. These contractions were absent in reserpinized RSS. Reserpinization reduced the potentiation after tricyclics and DMI was unable to enhance maximal concentrations of 5-HT, i.e. the post receptor effect of DMI seems to have been abolished. It is concluded that whilst the tricyclics may be irreversible antagonists of 5-HT in the guinea-pig ileum, they potentiate the effect of 5-HT in the RSS by uptake inhibition, and, in the case of DMI, some additional post-receptor effect. PMID- 4026458 TI - Calcium blocking properties of piprofurol. AB - Piprofurol is a benzofuran chalcon derivative. It was studied under various experimental conditions which allow the recognition of calcium antagonistic activity. Piprofurol inhibited in a concentration-dependent manner the calcium induced contractions in isolated potassium depolarized preparations of rat aorta (pA2: 9.29) and relaxed the K+-induced contraction of the dog coronary artery and the rabbit basilar artery (IC's 50: 2 10(-8) M; 3 10(-9) M). Piprofurol also inhibited noradrenaline-induced vascular smooth muscle contractions but the antagonism was clearly noncompetitive and the contractions induced were altered by concentrations two orders of magnitude higher than the concentration inhibiting calcium-induced contractions. Calcium antagonism was demonstrated in cardiac muscle: calcium mediated slowly rising action potentials were evoked in partially depolarized guinea-pig papillary muscle by electrical stimulation in the presence of isoprenaline. Piprofurol decreased the rate of rise of these slow action potentials. The inhibitory effect was reversed by an elevation of the calcium concentration in the bath fluid. Piprofurol exerts a negative inotropic effect (IC50: 5 10(-6) M) on guinea-pig papillary muscle. The ratio IC50 inotropic action/IC50 relaxant activity was 230, i.e. higher than that obtained with verapamil or diltiazem, and near that observed for cinnarizine. The pharmacological profile from in vivo dog experiments is in agreement with its in vitro properties: coronary sinus blood flow was increased and heart rate decreased. These effects suggested a potentially anti-ischaemic activity. This is confirmed in anaesthetized dogs, where piprofurol reduced the epicardial ST segment elevation following coronary artery occlusion, and in isolated heart preparations, where it decreased the leakage of LDH during periods of anoxia and reoxygenation. PMID- 4026459 TI - Comparative antiarrhythmic and local anaesthetic effects of piperazine citrate and lignocaine hydrochloride. AB - The effect of pretreatment with lignocaine hydrochloride (0.1 mg/g body weight) and piperazine citrate (1 mg/g body weight) on the number of deaths due to ouabain (0.02-0.12 mg/g body weight) was determined in the toad. Lignocaine was at least 10 times more potent than piperazine. Considering the doses that gave 50% protection from the 100% deaths due to ouabain (0.09 mg/g), lignocaine was 14.8 times more potent, but it was 56-60 times more toxic than piperazine as shown by the LD50s in the mouse and toad. Lignocaine was also about 10 times more potent than piperazine in preventing electrically-induced arrhythmia in the isolated guinea-pig atrium suspended in low potassium Ringer-Locke solution. With regard to infiltration anaesthesia, lignocaine was about 158 times more potent than piperazine. Therefore the relative potencies of the antiarrhythmic activities of piperazine and lignocaine do not correlate with the relative local anaesthetic potencies. It was concluded that, although lignocaine is 10-15 times more potent than piperazine as an antiarrhythmic agent, piperazine should be a much safer drug and could have potential utility as a substitute for lignocaine as an antiarrhythmic agent. PMID- 4026460 TI - Involvement of peripheral dopamine receptors in the antihypertensive effect of a new ergoline derivative (355/1057). AB - Oral administration of a new ergoline derivative (355/1057) produced a sustained arterial hypotension in conscious SHR rats. This effect was inhibited by the centrally acting DA blockers haloperidol and pimozide and by domperidone, a DA antagonist that does not cross the blood brain barrier. On the other hand it was unaffected by alpha- and beta-adrenoceptor blockers or by indomethacin. Moreover, the hypertension induced by 355/1057 in pithed SHR rats was reversed to hypotension when its alpha-adrenoceptor stimulant activity was inhibited by yohimbine. In anesthetized dogs the hypotensive activity of 355/1057 was abolished by pimozide but not by propranolol. In anesthetized cats, pretreatment with haloperidol prevented both the hypotensive activity of 355/1057 and its inhibitory effect on sympathetic nerve activity. These overall data suggest that 355/1057 lowers blood pressure in different species mainly by stimulating peripheral dopamine receptors. PMID- 4026461 TI - Effects of indomethacin on plasma fibrinogen levels in rats with tissue injury. AB - The present investigation was designed to study the effect of indomethacin (5 mg kg-1 day-1) on plasma fibrinogen levels in laparotomized rats. Whereas tissue injury significantly increased plasma fibrinogen when compared to normal uninjured rats, indomethacin completely blocked that effect. Conversely, indomethacin did not prevent fibrinogen increase in laparotomized rats injected with epinephrine, with spinal cord transection + epinephrine or with adrenal medullectomy + epinephrine. Indomethacin or epinephrine administration to normal rats did not modify plasma fibrinogen. Taking into account that epinephrine is a key hormone in plasma fibrinogen response in laparotomized rats, and according to our results, prostaglandins might act by two possible pathways: 1) by decreasing of the pain threshold of the sensory nerve endings and stimulating sympathetic adreno-medullar system; 2) by entering into the blood stream and enhancing epinephrine action on plasma fibrinogen. It would appear that indomethacin inhibits both pathways. PMID- 4026462 TI - The effect of dopamine, apomorphine and piribedil on the mesenterial blood flow of the cat. AB - Responses to i.v. administration of dopamine, apomorphine, piribedil and bromocriptine were investigated in the feline mesenteric vascular bed. Dopamine increases the mesenterial flow in doses of 0.3 to 30 micrograms/kg; its effect can be inhibited by 1 to 3 mg/kg of sulpiride. Apomorphine and piribedil also increased the blood flow, but only in 20 to 200 times higher doses; they show a tachyphylaxis phenomenon and their maximal activity is 32 and 59 per cent, respectively, that of dopamine. Apomorphine is a partial agonist of dopamine and can inhibit the activity of the transmitter amine. Bromocriptine has no activity on the feline mesenterial flow. The postsynaptic dopamine receptors of the cat can be characterized by the following: strong efficacy of dopamine and lower ones of apomorphine, piribedil and of sulpiride. The presynaptic dopamine receptors are involved mostly in the hypotension, they are activated by low doses of apomorphine, and piribedil and by higher doses of dopamine; sulpiride reacts with these receptors in much lower doses than with the postsynaptic ones. PMID- 4026463 TI - Effects of intracerebral morphine and enkephalins on the caudate-EEG spindle burst. AB - In an attempt to study the neural mechanisms of generation of the caudate-EEG spindle burst, effects of morphine, met-enkephalin and leu-enkephalin on the spindle were studied in gallamine-immobilized rats. The "caudate spindle" was significantly enhanced by microinjections of morphine and enkephalins into the lateral ventriculus, the thalamus, the midbrain reticular formation and the hippocampus but not the caudate nucleus, and the effects of these agents were completely antagonized by prior administration of naloxone. Intravenously administered morphine showed inhibitory actions on the neurons in the thalamus and the reticular formation and an excitatory effect on the hippocampal neurons. These results suggest that the enkephalinergic system may play an important role in the generation of the caudate spindle in the rat, i.e. as a positive modulatory system in the manifestation of the caudate spindle. PMID- 4026464 TI - Influence of naloxone on the antinociceptive effects of some antidepressant drugs. AB - The antinociceptive effects of tricyclic and atypical antidepressants were studied using the rat tail mechanical method. Clomipramine produced analgesia at the doses of 30 and 40 mg/kg, desimipramine at 10, 20 and 40 mg/kg, maprotiline at 20 and 30 mg/kg, mianserin at 30 mg/kg, nomifensine at 1, 2.5 and 5 mg/kg, indalpine at 10, 20 and 40 mg/kg, viloxazine at 60 and 80 mg/kg. Naloxone (0.8 mg/kg) abolished the antinociceptive action of these antidepressant drugs. These results suggest that the antinociceptive activity of these six antidepressant drugs in acute experimental pain could involve opiate mechanisms. PMID- 4026465 TI - Effects of phenobarbital, phorone and carbon tetrachloride pretreatment on the biliary excretion of acetaminophen in rats. AB - Rats with cannulated bile ducts excreted 24.6% of an i.v. dose of 100 mg/kg acetaminophen (AA) into bile within 8 hr, 0.9% as unchanged drug, 5.5% as sulfate, 15.1% as glucuronide and 3.1% as the glutathione conjugate. Pretreatment with phenobarbital (0.1% solution for 7 days instead of drinking water) significantly decreased the amount of total AA recovered in bile, to 12.8% mainly as a consequence of reduced glucuronide excretion (3.5%), whereas the GSH conjugate was augmented to 6.3%. Pretreatment with the GSH-depletor phorone (250 mg/kg i.p. 1 hr prior to AA) slightly reduced the total recovery of AA to 19.2%, due to a diminished excretion of the glucuronide (10.3%). Liver damage due to carbon tetrachloride administration (0.5 ml/kg p.o. 24 hr prior to AA) markedly decreased the total recovery of AA to 8.9% as a consequence of the reduction of the glucuronic acid (5.0%) and the GSH-conjugates (0.2%). These observations are discussed with respect to the effects of phenobarbital, phorone and CCl4 on microsomal and cytosolic GSH-dependent enzymes involved in the metabolism of AA. PMID- 4026467 TI - Analysis by microcomputer of the effect of capsaicin on pulmonary mechanics in the rat and guinea-pig. AB - Analysis of airways resistance and lung compliance in anaesthetized rats and guinea-pigs was accomplished on-line by microcomputer. In spontaneously respiring guinea-pigs capsaicin (0.5-2.5 microgram/kg i.v.) increased both resistance by 0.33 +/- 0.13 cmH20/ml/sec and the end-expiratory lung volume and it decreased compliance by 0.24 +/- 0.09 ml/cmH2O. These effects of capsaicin were resistant to vagotomy. In the rat, doses of capsaicin (40-80 micrograms/kg i.v. and i.a.) which produced respiratory apnoea had no effect on resistance or compliance in artificially ventilated animals but it did cause a decrease of end-expiratory volume, an effect which was abolished by vagotomy. The results confirm that reduction in tidal volume seen in spontaneously respiring rats following capsaicin (Mitchell et al., 1984) appears to be due to an action other than one on the bronchial calibre. PMID- 4026466 TI - A study of the effect of 8-aminoquinolines (primaquine, pamaquine, pentaquine) on the guinea-pig isolated ileum. AB - Primaquine (10(-6) to 4.10(-5) M), an antimalarial drug, has stimulatory effects on the guinea-pig ileum which seem to be related to stimulation of histaminergic H1-receptors. Preincubation of the preparations with compound 48/80 greatly inhibits the primaquine induced contractions, indicating that they should result from histamine release. On the other hand, primaquine (from 10(-6) M) like 2 other 8-aminoquinolines, pamaquine and pentaquine, has inhibitory properties on the intramural cholinergic neurones of the ileum, and at higher concentrations (10(-5) M) exerts a direct inhibition on the smooth muscle. PMID- 4026468 TI - Planning and protecting vascular access sites in the future hemodialysis patient. PMID- 4026469 TI - The aging thyroid. Thyroid deficiency in the Framingham Study. AB - In an unselected population of elderly (over age 60 years) men and women (the original cohort of the Framingham Study), the prevalence of thyroid deficiency, evidenced by a clearly elevated serum thyrotropin (TSH) level (greater than 10 microU/mL), was 4.4%. Women had thyroid deficiency (5.9%) more often than men (2.3%). Of those with clearly elevated serum TSH levels, only 39% had low serum thyroxine (T4) levels; the remainder had serum T4 levels in the lower half of the normal range. Others (5.9%) had a slightly elevated serum TSH level (5 to 10 microU/mL); their status was not clear, but more (12.7%) had low T4 levels than expected. The level of serum T4 was not a sensitive measure of thyroid deficiency nor was routine examination by a physician, even when the patient's background contained a clue to a possible thyroid problem. An elevated serum TSH level was a sensitive marker of thyroid deficiency in the elderly and was often the only way to detect it. Further studies are needed to determine the relationship of thyroid deficiency to cognitive and cardiovascular function in older persons. PMID- 4026470 TI - Lactate dehydrogenase-6. A biochemical sign of serious hepatic circulatory disturbance. AB - I confirmed the existence of an additional isozyme band of lactate dehydrogenase (LD) (EC 1.1.1.27) cathodic to LD-5 utilizing agarose gel isozyme electrophoresis in seven patients. Three of the patients died of circulatory failure within three weeks after the isozyme was identified. Four patients survived after successful therapy for heart failure. The under-lying clinical condition was arteriosclerotic cardiovascular disease causing congestive heart failure with passive congestion of the major viscera. I performed biochemical analysis on the isozyme and found that it was extremely heat stable, was not immunoglobulin bound, and contained only M, not H, subunits. It may represent a posttranslationally modified LD-5 or alcohol dehydrogenase. PMID- 4026471 TI - Intravenous streptokinase for thrombolysis of occluded arteriovenous access. Its use in patients undergoing hemodialysis. AB - Thrombosis of arteriovenous access is a major cause of morbidity in the patient population undergoing hemodialysis. This investigation utilized the technique of infusing streptokinase directly into the afferent limb of an occluded graft or fistula to restore patency. A total of seven patients was studied, one patient on two separate occasions nine months apart. Total clot lysis was observed in five of eight infusions. Partial clot lysis was seen in two of eight infusions, although one of these patients required thrombectomy to ensure persistent functioning of the fistula. One of the eight episodes was unsuccessful. A postinfusion fistulogram was performed on seven of eight occasions and demonstrated partial clot lysis in two patients or a stenotic lesion requiring surgical revision in two other cases. In conclusion, streptokinase infusion into the thrombosed vascular access appears to be a safe and efficacious technique for this patient population. PMID- 4026472 TI - Long-term follow-up of diabetic patients using insulin infusion pumps. Considerations for future clinical application. AB - Current debate about the use of insulin infusion pumps in the treatment of diabetes mellitus is partly attributable to a lack of available data about the long-term course of patients who use pumps. We evaluated the course of our first 20 patients treated with insulin infusion pumps. Two or more years after the inception of therapy, only half of these patients were still using the insulin infusion pump. Psychosocial stresses, which affected glycemic control, were identified retrospectively in a majority of patients, but were not appreciated when pump therapy was initiated, despite our best attempts to do so. Mean hemoglobin A1 levels decreased significantly for the entire group and for the subgroup that did not discontinue pump therapy. These results suggest that insulin pump programs must have the resources to provide appropriate support for all candidates, including unsuitable candidates, who present for treatment with insulin infusion pumps. PMID- 4026473 TI - Red cell fragmentation syndrome with the use of subclavian hemodialysis catheters. AB - The red cell fragmentation syndrome can occur due to abnormalities of the heart or the blood vessels or vascular malformations. We describe three patients who developed symptomatic hemolytic anemia due to red cell fragmentation with the use of single-lumen subclavian hemodialysis catheters. Retrospective analysis of 75 other patients who had undergone dialysis through this catheter disclosed five additional cases. Red cell fragmentation appears to be associated with partial catheter occlusion by thrombus or development of a clot at the catheter tip or both. The fragmentation resolved in all cases on withdrawal of the catheter. All patients with this catheter should be closely monitored for the red cell fragmentation syndrome, and the catheter should be withdrawn if it develops. White cell fragmentation was also seen in one patient. PMID- 4026474 TI - Fiberoptic bronchoscopy in patients with hemoptysis and nonlocalizing chest roentgenograms. AB - We reviewed retrospectively the records of 45 patients undergoing fiberoptic bronchoscopy for hemoptysis in whom chest roentgenograms either were normal or showed only nonlocalizing findings. Follow-up was available for up to three years. In none of the patients was evidence of malignant neoplasms found either at the time of the initial evaluation or at the time of follow-up. This was true for all age groups and for smokers as well as nonsmokers. We conclude that routine fiberoptic bronchoscopy for hemoptysis is not necessarily indicated in patients like ours. Indications for this procedure in this type of case should be carefully weighed. PMID- 4026475 TI - Adult respiratory distress syndrome secondary to tularemia pneumonia. AB - Three patients with tularemia pneumonia developed adult respiratory distress syndrome and required positive end-expiratory pressure for adequate oxygenation. Rapid improvement was noted following appropriate antibiotic therapy, and mechanical ventilation was successfully discontinued after six to eight days. PMID- 4026476 TI - Endoscopic laser therapy for malignancies affecting the esophagus and gastroesophageal junction. Analysis of technical and functional efficacy. AB - Thirty consecutive patients with far-advanced cancer affecting the esophagus and gastroesophageal junction underwent palliative endoscopic neodymium-YAG laser therapy. No patients were excluded from treatment, regardless of age, extent of disease, or performance status. Sessions were performed every other day and concluded when an endoscope could be easily passed beyond the previously obstructed area. Treatment was completed in 3.3 sessions (seven days). Luminal patency was achieved in 97%, but did not always equate with functional success. Seventy percent (21 patients) were able to ingest all necessary calories and leave hospital for home (functional success). Reasons for discrepancy between technical success and functional success included radiation-induced pharyngeal dysphagia, anorexia, painful tumor load and debility, and treatment complications. Endoscopic laser therapy of far-advanced esophageal or gastroesophageal junction carcinoma was almost always technically feasible, with relatively low morbidity. While technical success could not always be equated with functional success, therapy was "completely" functionally successful in 70% of patients with far-advanced disease. Poor performance status at accession correlated best with poor functional outcome. PMID- 4026477 TI - Computed tomography in diagnosis and management of multiple myeloma and its variants. AB - The use of computed tomography (CT) was evaluated in 25 patients with multiple myeloma, six with extramedullary plasmacytoma, and two with undiagnosed lesions. We found that CT was useful for (1) patients with multiple myeloma who had bone pain but normal roentgenograms, (2) patients with an M-protein, bone marrow plasmacytosis, and back pain from osteoporosis and compression fractures but an inconclusive diagnosis of multiple myeloma, (3) the determination of extent of tumor, and (4) guidance in needle biopsy. PMID- 4026478 TI - Propoxyphene and acetaminophen mixture (Darvocet)--related radiation-induced pneumonitis. AB - In a patient undergoing radiation therapy for recurrent, metastatic breast cancer, a mixture of propoxyphene and acetaminophen (Darvocet) was given for intercurrent viral infection. Discontinuation of therapy with this medication coincided with appearance of pneumonitis, reminiscent of the steroid withdrawal- related radiation pneumonitis. PMID- 4026479 TI - A case of carbimazole-induced intrahepatic cholestasis. An immune-mediated reaction? AB - A patient is described with cholestatic hepatitis following the use of carbimazole. A liver biopsy specimen showed intracanalicular cholestasis and some mononuclear cell infiltrate in the portal triades, consistent with drug toxicity; indications of an autoimmune or viral pathogenesis were absent. Rechallenge with the drug precipitated jaundice and disturbed liver function once more. Carbimazole induced a blastogenic response of patient lymphocytes in vitro. Both may suggest the involvement of an immune-mediated reaction, especially as it has been shown that sensitized lymphocytes may produce a cholestatic factor on stimulation with antigen. PMID- 4026480 TI - Immune hemolytic anemia associated with sulindac. AB - A number of adverse reactions have been associated with sulindac, a nonsteroidal anti-inflammatory drug, but acute hemolytic anemia associated with sulindac has not yet been reported, to our knowledge. We encountered two cases of severe immune hemolytic anemia, one fatal, which appear to have been related to sulindac. In vitro studies provided evidence that antibodies to sulindac and its metabolites were present in the serum of both patients. PMID- 4026481 TI - Stress-related sudden death. PMID- 4026482 TI - Mean red blood cell volume, narcotic addiction, and glucose tolerance. PMID- 4026483 TI - Cloxacillin-induced leukopenia. PMID- 4026484 TI - Interpretation of red blood cell indices by the nonhematologist. PMID- 4026485 TI - Is a smokeless society by 2000 achievable? PMID- 4026486 TI - The optimal antithrombotic dose of aspirin. PMID- 4026487 TI - Simple method for maintaining serum lidocaine levels in the therapeutic range. AB - Lidocaine hydrochloride is commonly infused intravenously to prevent ventricular arrhythmias. In some patients, elevations in serum lidocaine levels can cause serious toxic effects. In a group of 19 patients given a constant infusion of lidocaine, we confirmed the observation that serum lidocaine levels rose significantly between four and 24 hours after initiation of therapy. One of these patients manifested a toxic reaction to lidocaine. The lidocaine infusion rate was modified in a second group of 32 patients on the basis of the four-hour serum level. In these patients, after dosage adjustment, the mean lidocaine level did not rise, and all levels remained within the 2- to 4-mg/L therapeutic range at 24 hours. Without dosage adjustment, half of these levels would have fallen outside the desired range. A simple formula can be used to adjust prophylactic lidocaine infusion rates to attain levels that remain therapeutic, yet nontoxic. PMID- 4026488 TI - Long-term follow-up after recovery from acute myocardial infarction. Observations on survival, ventricular arrhythmias, and sudden death. AB - A long-term 12-year follow-up of 248 patients surviving acute myocardial infarction indicated a cumulative survival of 89%, 68%, 53%, and 45% for 1, 5, 10, and 12 years, respectively. When patients were assessed with five routinely obtained clinical factors, significant prognostic stratification of high- and low risk survival groups extended throughout the follow-up period. Sudden cardiac death was found to be twice as frequent as nonsudden cardiac death, but a significant relationship between sudden death and complex ventricular ectopic beats could not be defined. The extent of complex features of ventricular ectopic beats such as pairs, multiform, repetitive, and R-on-T was inversely related to survival. During the first year after acute myocardial infarction, frequency of ventricular ectopic beats was also inversely related to survival. A long-term effect of frequency on survival, however, could not be demonstrated. PMID- 4026489 TI - Time course of serum cardiac enzymes after intracoronary thrombolytic therapy. Creatine kinase, creatine kinase MB isozyme, lactate dehydrogenase, and serum glutamic-oxaloacetic transaminase. AB - We analyzed the time course of serum creatine kinase (CK), the CK MB isozyme, lactate dehydrogenase (LDH), and serum glutamic-oxaloacetic transaminase (SGOT) activity and calculated rates of increase and decline for CK in 24 consecutive patients with acute myocardial infarction (AMI) who received intracoronary thrombolytic therapy. In 19 patients with successfully reperfused infarcts, peak CK activity occurred at 14.1 +/- 1.1 hours after onset of symptoms, the maximal rate of CK rise was 595 +/- 102 IU/L/hr, and the fractional disappearance rate (Kd) was (86 +/- 6) X 10(-5)/min. The peak CK MB activity occurred at 12.9 +/- 0.8 hours and the MB Kd was (223 +/- 39) X 10(-5)/min. In five patients in the nonreperfused group the peak CK (24.9 +/- 4.5 hours) and CK MB (22.7 +/- 3.3 hours) activity occurred later, the maximal rate of CK rise (281 +/- 37 IU/L/hr) was less, and the CK Kd [(68 +/- 5) X 10(-5)/min] and MB Kd [(116 +/- 28) X 10( 5)/min] were lower. The peak CK, CK MB, cumulative CK release, and area under the curve were not different. Except for a shortened time to peak SGOT in the reperfused (17.1 +/- 1.3 hours) compared with the nonreperfused (29.1 +/- 5.6 hours) groups, the time course of LDH and SGOT were not different. Thus, the initial serum CK kinetics and time to peak SGOT may be useful in assessing the reperfusion status in patients with AMI receiving thrombolytic therapy without coronary angiography or in those who may have spontaneous recanalization. PMID- 4026490 TI - Aortic valve prolapse in congenital and acquired systemic disease. AB - Aortic valve prolapse, an uncommon finding in subjects with aortic insufficiency, occurred in one patient with rheumatoid arthritis and one with a congenital bicuspid aortic valve, conditions in which aortic insufficiency has been commonly attributed to aortic root dilatation and incomplete aortic valve closure, respectively. Aortic valve prolapse may be more commonly reported as the cause of aortic insufficiency in these conditions now that noninvasive techniques, such as echocardiography, are available. PMID- 4026491 TI - Magnesium toxicity as a cause of hypotension and hypoventilation. Occurrence in patients with normal renal function. AB - Symptomatic hypermagnesemia usually requires both increased intake of the ion and abnormal renal function; however, we treated two patients with iatrogenic hypermagnesemia (10.4 and 13.2 mEg/L) who had normal renal function. One received ureteral irrigation with hemiacidrin (Renacidin) to dissolve a stone, and the other was treated for ingestion of an unknown toxin with large doses of magnesium sulfate. Therapy included ventilatory support, intravenous calcium, and fluids. Dialysis was not required, and recovery was complete. PMID- 4026492 TI - Outpatient computer-based 32-hour esophageal pH studies teletransmitted to a central esophageal laboratory. AB - Using a computer-based 32-hour esophageal pH system with a small patient-worn digital recording computer, outpatient studies are performed in the physiologic environment of the patient's workplace and home. Samples are taken at 15-s intervals, and the pH data stored in this computer are then fed into the main computer in the Central Esophageal Laboratory for analysis, scoring, printing out, and storage. Satellite esophageal laboratories located in regional hospitals, clinics, and physicians' offices conduct pH studies by telecommunication, using antimony electrodes, a recording computer, and a modem to transmit data to the main computer for high-quality computer analysis. One main computer and associated personnel serve multiple satellite stations. This maintains patient-physician relationships and is highly cost-effective. PMID- 4026494 TI - Cardiac disability. The impact of coronary heart disease on patients' daily activities. AB - We studied 100 men with clinically stable coronary heart disease. Their capacity for exertion as defined by treadmill test was compared with the physical and social avocational activities they carried out in their daily routine, as reported by them. Exercise capacity (treadmill time) was strongly correlated with a physician's independent assessment of symptomatic status (anginal history). Although participation in some relatively strenuous elective activities was related slightly to exercise capacity, participation in many household duties and social undertakings bore no relationship to exercise capacity or to other measures of the severity of the underlying heart disease. The patients' own perceptions of their cardiac limitation varied for different activities and for some activities it was determined as much by their own concern and outside advice as by cardiac symptoms. Decreased capacity for exertion seems to exert surprisingly little influence on a cardiac patient's daily routine and interventions aimed at altering one of these measures of performance will not necessarily affect the other. PMID- 4026495 TI - Removal of therapeutic drugs by continuous arteriovenous hemofiltration. AB - Plasma and ultrafiltrate drug concentrations were determined for 17 drugs in ten patients receiving continuous arteriovenous hemofiltration. Ultrafiltrate concentrations were not always predictable because of multiple factors, which may include altered drug-protein binding in these very ill patients. PMID- 4026493 TI - The interpretation of the spirogram. How accurate is it for 'obstruction'? AB - The accuracy of the spirogram in detecting or excluding airway obstruction based on airflow limitation was assessed prospectively in 200 subjects, 74 with obstruction and 126 without it. The diagnosis of airway obstruction was based on a combination of clinical and body plethysmographic data. The ratio of forced expiratory volume in 1 s to forced vital capacity (FEV1/FVC %) had a sensitivity of 0.82 and a specificity of 0.98. A fixed lower limit seemed better than a lower limit based on prediction formulas. Because specificity is so much higher than sensitivity, less precise clinical information is required to confirm the presence of obstruction if FEV1/FVC % is abnormal than is needed to exclude obstruction if FEV1/FVC % is normal. Using a combination of FEV1/FVC % and the ratio of forced expiratory flow (FEF) at 50% of FVC gave a higher sensitivity with a comparable specificity when compared with FEV1/FVC % used alone. A normal value for FEF between 25% and 75% of FVC virtually ruled out obstruction, but low values had poor specificity. PMID- 4026496 TI - Hepatitis B virus in a cardiopulmonary resuscitation training course. Risk of transmission from a surface antigen-positive participant. AB - A group exposure to cardiopulmonary resuscitation training manikins contaminated by saliva from a participant during the immediate presymptomatic infectious stage of "e" antigen-positive hepatitis B recently occurred. None of the 18 susceptible participants developed serologic or clinical evidence of new hepatitis B infection during the six-month postexposure observation period. The risk of transmission in this setting appears to be low. Postexposure prophylaxis does not appear indicated. PMID- 4026497 TI - Intermittent left bundle branch block and associated T-wave abnormalities. PMID- 4026499 TI - Tyrosinemia II. A large North Carolina kindred. PMID- 4026498 TI - Magnesium depletion as a cause of refractory potassium repletion. PMID- 4026500 TI - Aggravated CNS depression with urinary retention secondary to baclofen administration. AB - A 74-year-old woman with a history of cerebrovascular disease developed profound central nervous system (CNS) and respiratory depression, generalized hypotonia, sinus bradycardia, and urinary retention following an increase in dose of baclofen, an antispasticity agent. Before receiving baclofen therapy the patient had had minor urinary dysfunction associated with a remote cerebrovascular accident but no urinary retention. Cessation of baclofen therapy and the relief of the urinary obstruction improved mental status and normalized motor function within 24 hours. A withdrawal syndrome of agitation, hallucinosis, and convulsive activity persisted for eight days following discontinuation of the baclofen. Our experience suggests that patients with various forms of CNS disease states may be at risk of serious CNS depression with even small therapeutic doses of baclofen. PMID- 4026501 TI - Improved oxygenation after muscle relaxation in adult respiratory distress syndrome. AB - Arterial blood oxygenation improved repeatedly after sedation and paralysis in a 27-year-old woman requiring mechanical ventilation for the adult respiratory distress syndrome. Oxygen consumption and cardiac output decreased proportionately after paralysis so that the partial pressure of oxygen in mixed venous blood remained unchanged. Paralysis eliminated inspiratory distortion of the airway pressure waveform and prevented forceful use of expiratory musculature. A flow-related reduction of venous admixture or recruitment of lung volume may best explain the beneficial effect of muscle relaxation on arterial saturation. PMID- 4026502 TI - Streptokinase therapy of pulmonary emboli with heparin-associated thrombocytopenia. AB - A 59-year-old man developed pulmonary emboli with heparin-associated thrombocytopenia. He was treated simultaneously with intravenous streptokinase and oral warfarin sodium. He responded with complete resolution of perfusion defects on lung scan and did not have any hemorrhagic or thrombotic problems. Although optimal therapy for patients with heparin-associated thrombocytopenia and thrombosis is unknown, fibrinolytic therapy may be useful despite thrombocytopenia, provided appropriate resources are available for careful patient monitoring and transfusion therapy. PMID- 4026503 TI - Thromboangiitis obliterans associated with idiopathic hypereosinophilia. AB - A 47-year-old male smoker with chronic eosinophilia developed progressive ischemia in his extremities. Pathologic examination of vessels in amputated limbs revealed changes of thromboangiitis obliterans. Focal segments of some arteries, however, revealed infiltration of thrombus and vessel wall by eosinophils. Furthermore, the patient developed a totally occluded right temporal artery, which on biopsy specimen showed marked infiltration by eosinophils within the vessel wall. In contrast to most patients with the hypereosinophilic syndrome, however, this patient had no evidence of endomyocardial thrombosis or fibrosis. In view of recent evidence that eosinophil granule proteins are toxic to endothelial cells, the findings in this patient suggest the possibility that eosinophils may be involved in the pathogenesis of thromboangiitis obliterans. PMID- 4026504 TI - Mediterranean spotted fever in an American woman. AB - Mediterranean spotted fever is common in southern Europe, the Middle East, and North Africa, but is unknown in the United States. It has a clinical picture resembling Rocky Mountain spotted fever, but it is a milder disease. We report a case of Mediterranean spotted fever in a young American woman returning from Morocco and review the clinical picture of this disease. PMID- 4026506 TI - Myoglobinuria in neuroleptic malignant syndrome. PMID- 4026505 TI - Thyrotoxic thyroiditis after radiotherapy for Hodgkin's disease. AB - Exposure of the thyroid gland to ionizing radiation has been associated with a variety of abnormalities. Among these are tardive hypothyroidism and an increased risk of developing thyroid nodules and cancer. Although acute thyroiditis has been known to complicate radioactive iodine 131 therapy, it has rarely been associated with external beam irradiation. Thyrotoxic painless thyroiditis developed in two patients after mantle-field irradiation for Hodgkin's disease. PMID- 4026507 TI - Nortriptyline and protriptyline in hyperventilation. PMID- 4026508 TI - Warfarin-erythromycin interaction. PMID- 4026509 TI - Arterial occlusion with coils. PMID- 4026510 TI - Hypertension screening with inversion. PMID- 4026511 TI - Quinidine-induced lupus erythematosus. PMID- 4026512 TI - Pulmonary embolus. PMID- 4026513 TI - Nonpharmacologic treatment of hypertension. PMID- 4026514 TI - Kerosene-induced abscesses. PMID- 4026515 TI - Poor Mrs D., poor medicine. PMID- 4026516 TI - High incidence of carcinoma. PMID- 4026517 TI - Esophageal atresia without tracheobronchial communication in a 9 mm human embryo (Carnegie stage 16). PMID- 4026518 TI - [Characteristics of the dorsal surface of the human fetal tongue seen with the scanning electron microscope]. PMID- 4026519 TI - Motor units of the human abductor digiti minimi. PMID- 4026520 TI - Mucosal and submucosal veins of the human pharyngo-esophageal transition. PMID- 4026522 TI - A scanning electron microscopic study of the mesencephalic trigeminal nucleus in duck and rabbit. AB - The mesencephalic trigeminal nucleus (MTN) cells of both young and adult ducks as well as of rabbits were investigated by scanning electron microscope. The rabbit showed only ovoid unipolar cells, while the duck also presented polyhedral cells. Few of these latter revealed processes originating from their surface and were recognized as multipolar cells. Some differences between the MTN cell surface of young and adult ducks were noticed. Synaptic bulbs were observed on the MTN cells in both duck and rabbit. PMID- 4026521 TI - Differential action upon sleep states of ventrolateral and central areas of pontine tegmental field. AB - In order to study oral pontine mechanisms of the sleep- wakefulness cycle (SWC), modifications in the total amount, frequency, and duration of episodes of wakefulness (W), drowsiness (D), slow sleep (SS) and paradoxical sleep (PS) together with modifications in the hourly distribution of both sleep states were analyzed in 15 adult cats. Three animals were used as sham-operated controls. Six of them, Group I, received unilateral lesions in ventral and lateral areas of the nucleus reticularis pontis oralis (RPO) and rostral nucleus reticularis pontis caudalis (RPC). The remaining 6 cats, Group II, had unilateral lesions in the central part of the same nuclei. After ventrolateral lesions (Group I) decrease of PS and SS occurred, but only PS changes reached statistically significant values; while, on the contrary, a significant increase of SS and PS followed central lesions (Group II). Hourly distribution analysis indicated that in Group I decrease of both sleep states took place mainly at night, while in Group II increase of both SS and PS occurred during day. These results suggest a complex and non- uniform influence of the pontine tegmental area on SWC mechanisms. Effects obtained after unilateral lesions, precisely located in ventral and lateral or central parts, point to the existence of two functionally distinct, although almost overlapping, systems, at this level. PMID- 4026523 TI - Hypoglossal high threshold afferents projecting to the secondary somatosensory area in the cat. AB - Recording with microelectrodes in the anterior ectosylvian area of the cerebral cortex in cats showed responses on stimulation of the hypoglossal nerve. The responses persisted after cutting the hypoglossal rootlets close to the brainstem but disappeared after cutting the glossopharyngeal and vagal roots. The responses were high threshold and probably mediated by "pain fibers". PMID- 4026524 TI - Tonic facilitatory influences of dorsal pontine reticular structures on the response gain of limb extensors to sinusoidal labyrinth and neck stimulations. AB - Experiments were performed to find out whether changes in resting discharge of the inhibitory reticulospinal (RS) neurons of the medulla, produced either by selective destruction or by cholinergic activation of a pontine tegmental reticular system, may modify the response gain of limb extensor muscles to given parameters of roll tilt of the animal or neck rotation. In precollicular decerebrate cats, an electrolytic lesion of the dorsal aspect of the pontine tegmentum, which slightly increased the tonic contraction of limb extensors, greatly decreased the amplitude of the multiunit EMG response of forelimb extensor muscles, i.e. of the medial head of the triceps brachii, to roll tilt of the animal and neck rotation (at 0.15 Hz, +/- 10 degrees), leading to selective stimulation of labyrinth or neck receptors. Correspondingly, the response gain of the forelimb extensors to labyrinth and neck stimulation decreased, but no change in the phase angle of the responses was observed. These findings did not depend on the increased postural activity, since they were still observed in the absence of any change in spontaneous EMG activity of the triceps brachii following the lesion. The changes in posture as well as in response gain of the forelimb extensors to labyrinth and neck stimulation produced by the pontine lesion appeared suddenly, and persisted for several hours throughout the survival period. Moreover, these changes involved mainly, but not exclusively, the limbs ipsilateral to the side of the lesion. Histological controls indicated that the structure responsible for the postural and reflex changes described above corresponded to the dorsal aspect of the pontine tegmentum located immediately ventral to the locus coeruleus (LC); this area corresponded to the peri-LC region as well as the surrounding pontine reticular formation (RF), including the dorsal aspect of the central tegmental field. This region closely corresponds to the area from which a tegmentoreticular tract, ending on the medullary inhibitory area, originates. It was previously shown that unilateral or bilateral lesion of the LC, which decreased the extensor tonus in the ipsilateral limbs, greatly enhanced the response gain of the triceps brachii to sinusoidal stimulation of labyrinth and neck receptors. These findings were attributed to suppression of an inhibitory influence that the LC exerts on the dorsal pontine reticular structures described above.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 4026525 TI - Observations on the cerebello-hypothalamic projection, with comments on non somatic cerebellar circuits. AB - The circuits responsible for cerebellar influences on nonsomatic responses have remained largely unknown. This report reviews some recent findings and present new data concerning pathways probably involved in this aspect of cerebellar function. A projection from the cerebellar nuclei to the hypothalamus was described several years ago, and a direct projection from hypothalamus to the cerebellum has recently been reported (6, 7, 8, 14, 15, 16). The present study gives evidence that the projections between hypothalamus and the cerebellar nuclei are at least in part reciprocal. The discovery of such reciprocal connections introduces new routes through which the cerebellum may directly interact with non-somatic centres and offers a more complete picture of the circuits which may be responsible for cerebellar modulation of visceral activity and certain aspects of affective behavior. The demonstration of such circuits indicates that the cerebellum acts as a general modulator and coordinator of a variety of activities, many of which are non-somatic in nature. PMID- 4026526 TI - Role of the pulvinar-lateralis posterior nucleus complex (P-LP) in the experimental epilepsy of the cat. AB - The ability of the pulvinar-lateralis posterior nucleus complex (P-LP) to evoke epileptic activity when stimulated, was studied in 20 adult cats. Twelve animals were analyzed after they recovered from the surgical procedure (chronic model). In seven of them a cannula with electrodes was implanted in the P-LP and one twisted bipolar electrode was placed ipsilaterally in the following structures: hippocampus, superior colliculus, caudate nucleus and cerebral cortex. Through the cannula Na penicillin was injected. The electrodes allowed both to stimulate and to record the electrical activity. In the remaining five cats, the cannula was implanted in hippocampus in order to compare its sensitivity to generate epileptic activity to that of P-LP. Another group of eight cats were surgically implanted and studied in the same day (acute model). In four of them the cannula was placed in the P-LP through the temporal pathway, to avoid crossing the hippocampus and the ventricle. In another four, penicillin was injected in the P LP after suctioning the cerebral cortex and the hippocampus overlying the former structure. Epileptic activity could be induced in P-LP and it spread rapidly to hippocampus and after a while to the other implanted structures. This was observed both with penicillin and electrical stimulation. The sensitivity of P-LP to generate epileptic activity was lower than that of the hippocampus. In particular, it was necessary to use two to ten times more penicillin and three times the electrical current intensity in the P-LP as compared to the values needed in the hippocampus. These results are discussed in view of the controversial problem about the ability of the thalamus to generate and spread epileptic activity. PMID- 4026527 TI - [Development of a Spanish scale for the evaluation of aphasia]. PMID- 4026529 TI - [Schizophrenia as a psychosomatic expression of mental disease. Reality of a single psychosis]. PMID- 4026528 TI - [Acute hemiplegia in childhood]. PMID- 4026530 TI - [Alcohol programs in a general hospital]. PMID- 4026531 TI - Erythropoiesis in mice with chemically-induced tumor. AB - The erythropoietic response of Strain A mice with benzo(a)pyrene-induced fibrosarcoma has been studied. The rate of erythropoiesis, expressed in terms of 59Fe incorporation into circulating erythrocytes, was slightly increased in the fibrosarcomatous mice compared to the matched controls. The femoral marrow of the tumor hosts became hypocellular with reduced number of erythroblasts. The spleen, on the other hand, was hypercellular with an increased number of erythroid progenitor cells. Quantitative assessment of erythropoietic activity in the hematopoietic organs by measuring the 6-hr organ uptake of 59Fe revealed erythropoietic suppression in the marrow but enhancement in the spleen following tumor development. While the number of CFU-s in the femoral marrow of the tumor bearing animals was slightly increased, marked increase in the concentration as well as absolute number of CFU-s was found in the spleen. Bioassay for erythropoietin revealed appreciable increase in the level of plasma erythropoietin in the tumor-bearing animals. PMID- 4026532 TI - Quality control study for estradiol receptor determination. AB - Lyophilized calf uterine cytosol standards for estradiol receptor (ER) were prepared separately in two institutes. The ER binding capacity was determined by dextran-coated charcoaL (DCC)-technique using a multi-point Scatchard analysis. The intra- and inter-assay coefficient of variation determined on the Hungarian preparation were 13.10% and 14.70%. The dissociation constant (Kd) values of all the samples ranged between 1.2 X 10(-9) M and 9.35 X 10(-10) M. Standards stored at--70 degrees C and at 0-4 degrees C proved to be stable for several months. At ambient temperature, a progressive decline of the ER activity was observed during a 1 year storage period. The use of the lyophilized calf uterine cytosol standards stored at 0-4 degrees C is recommended for both intra- and inter laboratory quality control study in multicentric clinical trials of breast cancer. PMID- 4026533 TI - Some aspects referring the methodology of estradiol receptor investigations for clinical purposes. AB - During the last years it had been tried to standardize the dextran-coated charcoal method for estradiol receptor determinations in the field of investigations of mammary tumor tissue probes intensively. But disintegration and homogenization of the tissue had not rendered enough attention in this connection. We could show that intensive homogenization procedures result in worse saturation curves in contrast to sparing procedures if parallel tissue probes were investigated. Therefore the application of a sparing homogenization seems to be an important precondition to get a correct determination of estradiol receptors in human breast cancer tissues. PMID- 4026534 TI - Homolytic substitution and carbenoidic reactions in the preparation of benzimidazole derivatives of pharmaceutical interest: synthesis and properties of (2-cycloalkyl-1-benzimidazolyl)-N,N-diethylacetamides. PMID- 4026535 TI - Potential antitumor agents, XIV. 1,8-Disubstituted anthraquinones. PMID- 4026536 TI - [Actions of new iminium compounds on selected bacterial and fungal strains. 10. Synthesis of N-alkoxymethylquinolinium chlorides and their derivatives]. PMID- 4026537 TI - Studies on potential antiviral compounds, XXIV. New 1-substituted isatin beta thiosemicarbazones. PMID- 4026538 TI - Hydroxy-3-(hydroxyphenyl)indoles. Relationship between structure and estrogen receptor affinity. PMID- 4026539 TI - Synthesis of 1,5-dihydro-5-(4-methoxyphenyl)-4H-pyrazolo[3,4-d]pyrimidin-4-ones and their ribosides and Mannich bases. PMID- 4026540 TI - [A one-step process for the preparation of gamma-ylidene-alpha,beta-butenolides]. PMID- 4026541 TI - [14C-labeling of alifedrine hydrochloride, a new positive inotropic compound]. PMID- 4026542 TI - [Spectrophotometric determination of cation- and anion-active constituents of drugs following ion pair extraction]. PMID- 4026543 TI - [Quinazolinones. 3. Synthesis, pharmacology and structure-activity relationship of derivatives of 2-methyl-3-(4-oxo-3-phenyl-thiazolidin-2-ylidenamino)-4(3H) quinazolinone]. PMID- 4026544 TI - [Synthesis and antihypertensive activity of quinazolinone derivatives]. PMID- 4026545 TI - Syntheses of 7Z,9E,11Z,14E-leukotrienes, biologically highly active SRS compounds. PMID- 4026546 TI - [Protein binding of drugs in continuous ultrafiltration. 6. Protein binding of acenocoumarol]. PMID- 4026547 TI - Cognitive dysfunction and mild closed head injury in traumatic spinal cord injury. AB - Previous investigators have reported that 25%-50% of traumatic spinal cord injury (SCI) patients sustain loss of consciousness (LOC), posttraumatic amnesia (PTA), or both concurrently with their SCI. A LOC of 20 minutes or less, or a PTA of 24 hours has been associated with prolonged time off work, and deficits in attention, concentration, memory, and judgment. Consequently, many traumatic SCI patients may also be the victims of a concomitant closed head injury (CHI) with cognitive sequelae. To test this hypothesis, a prospective study was conducted of 30 consecutive trauma-related SCI patients admitted to the Rehabilitation Institute of Chicago to determine the incidence of CHI and cognitive dysfunction (CD). The Halstead Category Test (HCT) was administered to each patient between 8 and 12 weeks after injury, and was considered abnormal if the patient committed 51 or more errors. Fifty-seven percent (n = 11) of all patients had abnormal HCT scores suggestive of higher level cognitive dysfunction. Patients with a new CHI had a mean HCT score of 65.2, as compared to 63.5 for patients with a premorbid CHI, and 46.3 for patients without a history of CHI. Although there was a trend toward higher HCT scores in patients who had any history of CHI, these differences did not reach statistical significance. The results of this study suggest that many trauma-related SCI patients are at risk for CD eight weeks after injury. Such cognitive abnormalities would be expected to impede rehabilitation and retard the requisite learning of new skills. PMID- 4026548 TI - Prediction of rehabilitation status of young adults with cystic fibrosis. AB - This study determined the relationship between vocational and educational plans, work values, vocational choice, awareness of occupational requirements, intelligence, self-esteem, and clinical severity of patients with cystic fibrosis and their school and vocational status six years after hospital clinical evaluation. Initially, 52 adolescents were tested on the Goldberg Vocational Development Scale, the Army General Classification Test, Tennessee Self-Concept Scale, and the Shwachman-Kulczycki System of Clinical Evaluation. Six years later each patient was sent a questionnaire to determine current school and employment. All data were subjected to intercorrelations (Pearson and biserial r) and analysis of variance. Eighteen survived and 15 responded. Ten were working in a variety of professional, semi-professional, and clerical jobs, two were unemployed due to cystic fibrosis, and three were still attending college. Of the 15, eight had graduated from college, nursing, or graduate school; one graduated from high school; three were full time students; and three were parttime students. The best predictors of school status were severity of illness (r = 0.55, p less than 0.01), and higher self esteem (r = 0.43, p less than 0.05). No single measure predicted work status. In a two-way analysis of variance using clinical severity and the average vocational development score, the main effect for severity (F = 4.19, p less than 0.05) was significant for student, but not for work status. It was concluded that the most powerful predictor of current student status was mild severity. PMID- 4026549 TI - Social functioning assessment in stroke patients. AB - The influence of depression, intellectual function, and physical impairment on patient reports of social functioning was assessed by comparing responses obtained from 30 stroke patients with those obtained from an outside informant who knew the patient well. There was relatively good agreement between patient and other for both the overall score on the Social Functioning Examination (SFE) and individual items related to specific aspects of social functioning. Differences between scores obtained from a patient and outside informant were not significantly related to either depression, moderate degrees of intellectual impairment, relative closeness of patient and informant or to degree of physical impairment. These data suggest that valid SF assessments can be made either by a stroke patient who is capable of being interviewed or by a familiar outside informant. In addition, the prognostic utility of the SFE was examined by interviewing 50 patients during the acute stroke period and following them over six months. Social functioning in-hospital scores were not found significantly related to 6-month scores for either depression, intellectual impairment, or physical impairment, but depression and in-hospital impairment significantly predicted social functioning at 6-month follow-up. These data suggest that the most impaired stroke patients are the most likely to undergo social deterioration during the post-stroke period and may require the greatest amount of social intervention. Whether treatment of these variables significantly affects 6-month outcome remains an intriguing question for further study. PMID- 4026550 TI - Spinal cord injury: its short-term impact on marital status. AB - We have had the impression that patients with spinal cord injury (SCI) experience fewer marriages and more divorces than their noninjured counterparts. To test this impression statistically, we examined the influence of SCI in association with other select variables on the marital status of 276 patients injured between 1973 and 1980 and treated at the University of Alabama in Birmingham Spinal Cord Injury Care System. The expected numbers of marriages and divorces in the study population were based on comparison with reported marriage and divorce rates for the general US population. Discriminant analysis was employed to identify variables associated significantly with a postinjury change in marital status. Substantially fewer marriages and more divorces occurred than were expected (p less than 0.05). No variables were associated significantly with marrying within three years of injury. However, divorcing patients were significantly more likely to be young black women who had been previously divorced, had no children, and had Barthel scores of less than 80. Using the most effective combination of these variables, 38.7% of the variance was explained, and the postinjury marital status of 81.5% of patients married at injury was predicted correctly. While other determinants of postinjury marital status undoubtedly exist, the likelihood of divorce can be assessed using a comparatively small set of predictor variables. PMID- 4026551 TI - Functional changes in vascular amputee patients: evaluation by Barthel Index, PULSES profile and ESCROW scale. AB - This study evaluated the changes made by 60 peripheral vascular amputees from one month prior to admission to six months after attending a rehabilitation hospital. The Barthel index, PULSES profile, and ESCROW profile were used to measure functional status, social support, and rehabilitation progress. Statistical analysis consisted of t-tests to determine significant differences between the means of scores at varying intervals, and analysis of variance was added to determine interactions between amputation level, age, and sex as related to functional change. Amputees showed significant gains in Barthel scores from admission to discharge; this was attributed to rehabilitation intervention. They showed a significant decrease by the PULSES profile over the study period, indicating a decrease in independence from their premorbid function. Changes in ESCROW scores showed patients to have a greater need for social supports as they moved from admission to discharge. Age was a significant factor in mobility at discharge as measured by the Barthel index. As measured by the PULSES profile, men did better than women at six months follow-up. Unexpected results were that neither amputation level nor the presence or absence of diabetes mellitus had a significant impact on functional status as measured. The lack of significant differences by amputation level may be due to factors of age and sex, as well as to more depression in the below-knee group. PMID- 4026553 TI - Multiple primary epidermoid carcinomas of the upper aerodigestive tract. AB - In a series of 405 patients with epidermoid carcinoma of the head and neck, 52 patients (13%) developed multiple epidermoid carcinomas of the upper aerodigestive tract. Subsequent primary tumors developed with nearly equal frequency in the head and neck, lung, and esophagus. Forty of the patients developed a subsequent primary carcinoma within five years of the first. Thirty eight (73%) of the patients who developed a subsequent primary carcinoma survived less than two years from its diagnosis. The majority (34/50) of the patients died from the subsequent primary carcinoma. We recommend that panendoscopy and an esophagogram be performed on initial evaluation of patients with head and neck cancer. A thorough reexamination is warranted if new symptoms or signs develop. PMID- 4026552 TI - Use of the long tube in the management of patients with small-intestinal obstruction due to adhesions. AB - A retrospective analysis was performed of all patients admitted to our hospital over a six-year period with a diagnosis of small-intestinal obstruction due to adhesions, to assess the efficacy of treatment with long-tube decompression. Of 127 episodes of obstruction, two thirds responded to nonoperative treatment. Factors that were associated with a greater likelihood of success with long-tube decompression included incomplete obstruction, recurrent obstruction, and passage of the tube beyond the pylorus. Clinical findings were relatively reliable as diagnostic indicators of strangulation. The overall mortality was 1.5%, with no deaths due to a delay in operative intervention. A trial of long-tube decompression is recommended in patients presenting with a diagnosis of small intestinal obstruction due to adhesions in the absence of clinical evidence of strangulation. PMID- 4026554 TI - Elemental diet as prophylaxis against radiation injury. Histological and ultrastructural studies. AB - We investigated whether elemental diet feeding would protect the intestine from radiation injury. Five dogs were fed an elemental diet for three days before receiving pelvic irradiation (500 rad/day for four days) and were maintained on the diet during the days of irradiation. These dogs were compared with five dogs that were fed normal kennel ration, but were treated similarly otherwise. One day and five days following completion of the radiation treatment, the dogs were anesthetized and a biopsy specimen of terminal ileum was taken for histologic and electron microscopic studies. In the dogs fed the elemental diet, there was no significant damage to the intestine seen on histological examination, and electron microscopy disclosed elongated microvilli and no organelle damage. However, both histological and electron microscopic examination of the intestine from dogs maintained on normal kennel ration showed that severe damage had occurred from the irradiation procedure. It seems, therefore, that the feeding of an elemental diet to dogs as a prophylaxis can afford protection to the intestine from the acute phase of radiation injury. PMID- 4026555 TI - Left renal vein division in abdominal aortic aneurysm operations. Effect on renal function. AB - We examined the effect of left renal vein (LRV) division during abdominal aortic aneurysm operations on renal function during the recovery period. Fifteen patients with LRV division were compared with 26 patients in whom the LRV was not ligated. These two groups of patients did not differ significantly in any of their preoperative characteristics, operative management, or postoperative complications. Preoperative, highest postoperative, and predischarge levels of plasma urea and creatinine, as well as urinary sediment, were compared in both groups. Left renal vein division could not be implicated as a cause of renal function deterioration and was found to be a safe, useful adjunct to abdominal aortic aneurysm surgery. PMID- 4026556 TI - Muscle prostaglandin production in the rat. Effect of abdominal sepsis and different amino acid formulations. AB - Recent in vitro studies attribute regulatory functions to prostaglandins (PGs) in muscle protein metabolism, particularly enhancing proteolysis. In the present study, the amount of muscle PG production from endogenous precursors was determined in control and septic animals (cecal ligation and puncture) that were infused with 5% dextrose or dextrose with three amino acid formulations differing in their branched-chain amino acid (BCAA) content. We could not detect any differences in prostaglandin E, 6-keto-prostaglandin F1 alpha, and thromboxane B2 production between control and septic animals. Furthermore, the infusion of BCAAs, which have previously been shown to be nitrogen sparing following injury, did not influence the production of any of the PGs studied in either control or septic muscle. It is likely that the effects of the BCAAs on muscle synthesis and degradation are independent of the PGs. PMID- 4026557 TI - Electric activity and motility in the side-to-side isoperistaltic ileal reservoir. AB - Twelve dogs underwent total colectomy and ileorectal anastomosis with construction of a side-to-side isoperistaltic ileal reservoir 20 cm long. The average stool frequency was 18 per 24 hours within the first two weeks after operation, decreasing to five per 24 hours at eight weeks. Stool consistency was liquid at two weeks, becoming semisolid at eight weeks. Saline absorption from a normal segment of ileum 20 cm long was 29 mL/hr. The average saline absorption from the reservoir was 74 mL/hr at four weeks and 106 mL/hr at eight weeks. The average volume of a 20-cm segment of ileum with an intraluminal pressure of 10 cm H2O was 69 mL. The average reservoir volume with the same intraluminal pressure immediately after construction was 203 mL, increasing to 458 mL at eight weeks. Frequency of slow electric waves in the normal canine ileum was 15.71/min, which decreased to 10.21/min immediately after construction of the reservoir. By eight weeks, the slow waves increased to 13.51/min. It appears that electric activity in the muscle of the isoperistaltic lateral ileal reservoir returns to near normal eight weeks after operation. Enlargement of the reservoir in the absence of severe distention does not appear to interfere with peristaltic activity. Stool frequency is reduced simultaneously when peristaltic activity returns and the reservoir enlarges. PMID- 4026559 TI - Emergency intravenous pyelography in the trauma patient. A reexamination of the indications. AB - Because of the high incidence of abnormal intravenous pyelograms (IVPs) in victims of blunt trauma undergoing resuscitation, a retrospective review of the Trauma Registry at the University of California, San Diego Medical Center, was undertaken to evaluate the indications for ordering this test. The charts of 216 patients were reviewed, all of whom had formal IVPs (four films) done as an emergency procedure at the time of admission. In this study, special attention was directed toward comparing both the degree of hematuria and the anatomic site of injury with the results of the IVP. A total of 20 renal injuries was detected by IVP. Of these injuries, all but one had hematuria that was greater than 50 red blood cells per high-power field. All but one of the abnormal IVPs were associated with obvious abdominal injuries. The results of the IVP influenced the clinical course of only one patient in the entire series. We conclude that the use of the formal IVP (four films) in the resuscitation phase of treating the multiply traumatized patient be reserved for those patients with penetrating abdominal injury or with hematuria consisting of greater than 50 red blood cells per high-power field. For any major blunt abdominal trauma without significant hematuria, a more simple and rapid study (one-shot IVP) to demonstrate bilateral nephrograms is probably adequate to rule out occult renal artery thrombosis. PMID- 4026558 TI - Pseudohyponatremia in acute hyperlipemic pancreatitis. A potential pitfall in therapy. AB - Six patients had apparent hyponatremia associated with hyperlipidemia and acute pancreatitis. To our knowledge, only one such patient with acute pancreatitis has previously been described, although the association of hyperlipidemia with "pseudohyponatremia" had been well documented. One of the above patients, whose condition was hemodynamically unstable on admission, developed dangerous symptoms of hyperosmolarity and cerebral dysfunction following aggressive resuscitation with hypertonic saline solution. The pseudohyponatremia results from displacement of water in the serum by the lipids, with sodium existing only in the aqueous phase. This volume displacement results in errors of sodium measurement when the latter is determined by flame photometry or indirect potentiometry, but not when determined by ultracentrifugation and direct potentiometry. PMID- 4026560 TI - Effects of gastrointestinal hormones on Oddi's sphincter and duodenal myoelectric activity and pancreatobiliary pressure. Studies in the opossum. AB - Myoelectric activity of Oddi's sphincter and duodenum was correlated with common duct and pancreatic duct pressures in conscious opossums after infusion of the following substances: cholecystokinin, pentagastrin, glucagon, secretin, and acetylcholine. Cholecystokinin and pentagastrin increased and glucagon and secretin decreased the frequency of spike potentials in Oddi's sphincter and the duodenum. Acetylcholine was associated with the largest increase in spike potentials in both Oddi's sphincter and the duodenum. Although there was variation in the number of pressure elevations related to Oddi's sphincter spike potentials, the baseline pressure remained constant during administration of the hormones. Acetylcholine infusion increased the biliary and pancreatic pressures to 29 and 31 mm Hg, respectively. We conclude that gastrointestinal hormones may have an important role in regulating the excretion of bile and pancreatic juice into the duodenum. PMID- 4026561 TI - A quality control analysis of aminoglycoside management. AB - Aminoglycoside administration practices were evaluated in a teaching hospital using three study methods: a chart review of 40 randomly selected patients receiving aminoglycosides was conducted retrospectively; 93 health care personnel involved in ordering and administering aminoglycosides to patients were interviewed regarding their understanding of aminoglycoside utilization practices; and ten patients having serum peak and trough aminoglycoside determinations were closely monitored for accuracy of dose administration and obtaining blood specimens at appropriate times. The chart review showed that during 15 of 32 evaluable therapy courses no determinations of serum aminoglycoside concentration were obtained. The survey demonstrated that only 24% of the residents actually used the results of peak and trough determinations to adjust dosage regimens. Direct observation of health care personnel disclosed only two of ten instances in which doses were administered and serum concentration specimens obtained with no apparent problems. Most personnel in our hospital were unaware of these pervasive suboptimal or inconsistent practices associated with aminoglycoside administration and interpretation of laboratory results. PMID- 4026562 TI - Further evidence supporting the existence of the celiac artery compression syndrome. AB - A 23-year-old man presented with prolonged postprandial epigastric pain and an epigastric bruit with systolic and diastolic components, the intensity of which decreased with inspiration as demonstrated by abdominal phonography. Arteriography demonstrated significant narrowing of the origin of the celiac artery. At operation, the origin of the celiac artery was found to be constricted by fibers of the median arcuate ligament of the diaphragm, and this ligament was divided. Intraoperative flow measurements demonstrated an increase in blood flow through the main branches of the celiac axis, after division of the ligament. Four years following successful surgery, the patient has continued to be in good health without symptoms, and the bruit has remained absent. Further abdominal arteriography has demonstrated the normality of the celiac artery. We believe this to be a well-proven case of the "celiac artery compression syndrome." PMID- 4026563 TI - Esophageal motor dysfunction in an adult with a congenital tracheoesophageal fistula. AB - A preoperative barium esophagogram and esophageal manometry in an adult patient with an H-type congenital tracheoesophageal fistula revealed the typical esophageal motor abnormalities previously described following operative repair of esophageal atresia in infants. The upper esophageal sphincter contracted normally, the lower esophageal sphincter relaxation was weak and incomplete, and there was no active peristaltic wave within the esophagus. These findings support the theory that the abnormal esophageal motor function reported after repair of congenital tracheoesophageal fistula and esophageal atresia is on a congenital basis and is not directly attributable to operative trauma or denervation. PMID- 4026564 TI - Endarterectomy and restenosis. PMID- 4026565 TI - Wash away a bellyache. PMID- 4026567 TI - Surgery in Haiti revisited. An opportunity for a general surgeon. PMID- 4026566 TI - Polytetrafluoroethylene grafts for leg ischemia: facts and fiction. PMID- 4026568 TI - Effect of monensin on fermentation pattern and soybean protein degradation in the rumen of sheep. AB - The effect of a daily dose of 30 mg Monensin on rumen fermentation pattern and degradation of the crude protein fraction of soybean meal was investigated with sheep. Degradation parameters for soybean meal were measured by the nylon bag technique. Monensin increased propionic acid percentages in the rumen, with a concomitant decrease in acetic- and butyric acid proportions, thus confirming earlier work. Ammonia N concentration in the rumen was also lowered, indicating an inhibitory effect on rumen protein breakdown. However, no effect on degradation rate, degradability and effective degradability (only with one sheep) could be observed. Possible reasons for these findings are discussed. Amino acid analysis on the residues in incubated bags revealed slight changes in amino acid composition, but these changes were considered to be nutritionally unimportant. PMID- 4026569 TI - Enhancement of radiation effects by mercury in preimplantation mouse embryos in vitro. AB - Mercuric chloride (3 microM or 10 microM) increased several effects of ionizing radiation (1 Gy) on preimplantation mouse embryos in vitro. Blastocyst formation, hatching of blastocysts, and the number of cells per embryo were affected by this increase in radiation risk. The formation of micronuclei, however, was not influenced either in experiments using mercury alone or in combination experiments with X-rays. Not only was the sum of the single effects exceeded in some of the combination experiments, but the dose-pairs, which were necessary for obtaining a certain effect, clearly fell to the left of the envelope of additivity. That is, the enhancement of effects cannot be explained merely by the shape of the dose-response curves, but there is an interaction between mercury and ionizing radiation. PMID- 4026571 TI - Study of inorganic arsenic methylation by rat liver in vitro: relevance for the interpretation of observations in man. AB - The biotransformation of inorganic arsenic by rat liver in vitro leads to the production of a monomethylated and a dimethylated arsenic derivative, measured by flameless atomic absorption as monomethylarsonic (MMA) and dimethylarsinic (DMA) acids respectively. The methylating activity is localized in the cytosol and accepts only As3+ as substrate. Its optimum pH lies between 7.5 and 8.0, and reduced glutathione (10(-2)M) is required for full activity. S-Adenosylmethionine is the essential methyl group donor and corrinoid derivatives act synergistically. An excess of substrate and the addition of mercuric ions prevent the formation of the dimethylated arsenic derivative without affecting that of the monomethylated compound. This indicates that two different enzymatic activities are involved in the methylation of inorganic arsenic in mammals. Previous observations in man (Buchet et al. 1981 b, 1984) and the results of the present study suggest that DMA production results from the subsequent methylation of the MMA precursor, although the possibility that metabolites are also produced by two completely independent pathways cannot yet be conclusively rejected. The kinetics of MMA and DMA production provide an explanation for the observations that in volunteers given increasing amounts of As3+, the urinary excretion of DMA levels off faster than that of MMA and in patients acutely intoxicated with As3+, several days may elapse before DMA becomes the preponderant metabolite. The results of the present study also suggest that the reduction of MMA production associated with an increased synthesis of DMA found in patients with liver diseases given a standard dose of As3+ might be due to a reduction of As3+ uptake by the liver cells. PMID- 4026570 TI - Reduction and binding of arsenate in marmoset monkeys. AB - The metabolism of 74As-arsenate (As V, 0.4 mg As/kg body weight, IV) in marmoset monkeys (two males and two females) was studied. Unlike all other animal species studied so far, the marmoset was found to be unable to metabolize the arsenate to dimethylarsinic acid. Most of the absorbed arsenate was reduced to arsenite (As III) in vivo. Only 20% was excreted in the urine as unchanged As V. A further 20% of the dose was excreted as As III. The rest of the As III produced was bound to the tissues, giving a distribution picture very similar to that reported earlier for marmoset monkeys given arsenite. The tissues with longest retention of arsenic were the liver, upper gastrointestinal tract (oral cavity and esophagus), skin, kidneys and gall bladder. The pronounced accumulation in the liver resulted from specific binding of arsenic to the rough microsomal membranes, unique to this animal species. PMID- 4026572 TI - Differential serum protein binding of benzidine- and benzidine-congener based dyes and their derivatives. AB - Environmental dyes and their derivatives, some of which are genotoxic, must be transported within the body to the tissues which they affect. One mechanism for this can be observed directly by crossed immunoelectrophoresis (X-IEP). Binding of these chemicals to certain serum proteins changes electrophoretic and immunoprecipitation morphology in X-IEP patterns. This is demonstrated here for four azo dyes derived from benzidine, 3,3'-dimethylbenzidine, and 3,3' dimethoxybenzidine, and their parent aromatic amines. Direct Red 2 (a 3,3' dimethylbenzidine-based dye), Direct Blue 15 (a 3,3'-dimethoxybenzidine-based dye), Direct Black 38 (a benzidine-based dye), and Evans Blue (a 3,3' dimethylbenzidine-based dye) all bound to albumin, alpha 1-lipoprotein, beta lipoprotein, and hemopexin. Direct Red 2 only slightly affected the mobilities of these proteins. Direct Blue 15 bound also to prealbumin and alpha 1 antichymotrypsin, and degraded C3 globulin. Direct Black 38 and Evans Blue bound to numerous additional proteins. Evans Blue bound variably to proteins of sera from different individuals, suggesting that there are individual differences in serum protein binding capabilities for these chemicals. Of the three derivatives of the benzidine dyes, only 3,3'-dimethylbenzidine caused changes in X-IEP patterns, indicating its binding to the serum proteins. This chemical differentially affected sub-populations of alpha 1-lipoprotein, either by altering its electrophoretic mobility or inhibiting its recognition by antibodies. Autoradiographic analyses demonstrated the binding of benzidine and 3,3'-dimethylbenzidine to both alpha 1- and beta-lipoproteins. PMID- 4026573 TI - Metabolism and mutagenicity of aromatic amines by human fetal liver. AB - Human fetal liver microsomes were found to metabolize the carcinogen 2 acetylaminoflurene (AAF), the major metabolite being the deacetylated product 2 aminofluorene (AF). On the other hand, N-hydroxy-2-acetylaminofluorene (N-OH AAF), a proximate carcinogenic metabolite, could not be detected. The human fetal liver samples converted AF and N-OH-AAF, but not AAF, to products mutagenic for S. typhimurium TA 98. PMID- 4026574 TI - The octanol/water distribution of mercury compounds. AB - Lipophilicity plays an important role in the biological action of mercurials. The distribution of one inorganic and five organic mercury compounds was determined in an n-octanol/water system. Lipophilicity decreased in the order CH3HgCl, bromomercurihydroxypropane, HgCl2, chlormerodrin, p-chloromercuribenzoic acid (PCMB), p-chloromercuriphenylsulfonic acid (PCMBS). The toxicity of mercurials, as reported in the literature, appears to parallel their lipophilicity. PMID- 4026575 TI - Dimethoate-induced toxic cardiac failure in the guinea pig. AB - In anaesthetized guinea-pigs treated with lethal doses of dimethoate, cardiac failure and serious ECG disturbances developed in the early phase of intoxication. The toxic cardiac phenomena appeared to be unrelated to the degree of cholinesterase inhibition, but showed a close correlation with myocardial dimethoate concentration. Cardiac failure and mortality were first observed at a critical pesticide level of about 110 micrograms/g, while a level of 221 micrograms/g resulted in death in all cases. The present investigation refers to the direct effect of the pesticide on the myocardium, independent of its anticholinesterase action. PMID- 4026576 TI - DNA-binding assay of methyl chloride. AB - Fischer-344 rats and B6C3F1 mice of both sexes were exposed in closed chambers to 14C-labeled methyl chloride. Different clearance values from the gas phase of the system indicated that, based on body weight, mice metabolized the test compound much faster than rats. After isolation of DNA and nucleoproteins from liver and kidneys radioactivity was found in all macromolecular samples; this was ascribed to metabolic C1-incorporation. Radioactivity incorporation was particularly high in DNA of mouse kidneys, suggesting a high turnover to active C1 bodies (formaldehyde, formate) in this tissue. Analyses of DNA samples from kidneys of female and male mice showed neither 7-N-methylguanine nor O6-methylguanine. Hence, the formation of tumors in B6C3F1 mice exposed to high concentrations of methyl chloride is not based on methylation of DNA in this tissue. PMID- 4026577 TI - Structure-acute toxicity relationship of dinitriles in mice. AB - Acute toxicity and metabolism of seven dinitriles in mice was studied in relation to the chemical structures. The oral LD50 for each nitrile was determined under different conditions for mice pretreated with either carbon tetrachloride (CCl4) or olive oil. All test nitriles were metabolized into cyanide in vivo and in vitro. The cyanide level was variable among the compounds (0.35-0.74 micrograms CN/g brain) at death in the brains of mice, the level for malono- and adiponitrile being comparable to that found in mice killed by dosing with potassium cyanide. After receiving each nitrile, the mean survival time of mice pretreated with CCl4 was prolonged and their brain cyanide level decreased when compared with the corresponding control. With malononitrile, the former did not significantly change and the latter decreased slightly. Brain cyanide levels of control mice at death showed a peak at the lower log P region, while those of CCl4-pretreated animals remained lower independently of log P, with the exception of malononitrile. Microsomal metabolism of nitriles to cyanide was greatly inhibited when microsomes were prepared from livers of mice pretreated with CCl4. The relationship between log (1/LD50-CCl4), LD50 in mice pretreated with CCl4, and log P fits a parabolic plot. PMID- 4026578 TI - Percutaneous absorption of [14C]methacrylamide in animals. AB - Percutaneous absorption of [14C]methacrylamide was determined in rabbits, rats and mice. Radioactivity in blood of rabbits increased rapidly after IV injection, after topical application with a cloth and after direct topical application of a 15 or 5% test solution, suggesting high permeability of the skin for methacrylamide. Radioactivity then began to decrease exponentially within 1 h. Tissue radioactivity 24 h after IV dosing was high in blood, liver and serum, and low in brain, nerve and muscle. The radioactivity was more uniformly distributed with the exception of liver, after application with a cloth and after direct contact than after IV dosing. When the application site was washed with water after direct application, decline of radioactivity in blood was accelerated slightly and a decrease in radioactivity in some tissues was found, although the difference between non-wash and wash groups was not significant in either the declining curve or the tissue radioactivity, with the exception of serum for the latter. Between 25 and 60% of the radioactivity found in tissues was protein bound after 24 h. Recovery of radioactivity in urine was highest after IV administration, intermediate after direct contact, and lowest after cloth application. Radioactivity in expired air and bile was small. Both radioactivity in tissues and its recovery in urine in rats, and tissue radioactivity in mice, were lower than in rabbits, when adjusted for dose per unit body weight, suggesting lower skin permeability for methacrylamide in the former species.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4026579 TI - Formation, toxicity and inactivation of acrolein during biotransformation of cyclophosphamide as studied in freshly isolated cells from rat liver and kidney. AB - In the present study the formation and the effects of cyclophosphamide-derived acrolein were investigated using isolated cells from rat liver and kidney, with particular regard to the protective action of low molecular weight thiols against cellular toxicity. The results may be summarized as follows: Cyclophosphamide (CTX)-mediated toxicity to isolated cells is dependent on cytochrome P-450 activity; Loss of viability in cells incubated with cyclophosphamide is preceded by a depletion of cellular GSH; Stimulation of cellular GSH synthesis or the presence of low molecular weight thiols in the incubation medium protects against cyclophosphamide-induced toxicity; Acrolein is probably formed extracellularly as well as intracellularly and can be detoxified by thiol compounds, forming a thiochemiacetal or a thioether. PMID- 4026580 TI - The major internal protein, p27, of a retrovirus-like particle is expressed in blood lymphocytes from psoriatic patients. AB - Retrovirus-like particles were isolated from the urine of a patient with psoriasis. The major internal protein, p27, in these particles was isolated by immunosorbent chromatography and gel filtration on a Sephacryl S-300 column in 6 M guanidine hydrochloride. The protein was purified to homogeneity as judged by SDS-PAGE. A hyperimmune serum with specificity for p27 was obtained by vaccination of a rabbit with purified p27 antigen. This antiserum was used to examine blood lymphocytes for the expression of p27 antigen by indirect immunofluorescence. Between 0.1 and 1 per cent of the lymphocytes obtained from patients with psoriasis showed a bright cytoplasmatic (and membrane) fluorescence while no p27 positive cells could be detected in the preparations from the healthy controls (frequency less than 0.01 per cent). Among the p27 positive psoriatic cells were lymphocytes with markers for T cells, B cells and NK cells. PMID- 4026582 TI - Maturation of measles virus hemagglutinin glycoprotein. AB - The processing of measles virus hemagglutinin glycoprotein (H) in infected cells was studied by pulse-chase method and two-dimensional isoelectric focusing and SDS-polyacrylamide slab gel electrophoresis. H glycoprotein was synthesized initially as polypeptides smaller than H glycoprotein present in the virions. They were then processed into a cohort of polypeptides of larger molecular size and with reduced charge. The change was associated with the expression of H glycoprotein on the cell surface. The removal of sialic acid from carbohydrate chain of H glycoprotein resulted in the shift of isoelectric point to a more basic range. The entire process of maturation of H glycoprotein required approximately 5 hours. Carbohydrate content in H was determined to be approximately 12 per cent by weight. Mannose, galactose, fucose, N acetylglucosamine, and N-acetylneuraminic acid were the constituent monosaccharides. PMID- 4026581 TI - Interaction of Newcastle disease virus strains differing in virulence with chicken red blood cell receptors. AB - Nine NDV strains belonging to lentogenic, mesogenic and velogenic groups were studied. Virus adsorption to chicken red blood cell (RBC) surface was performed at 4 degrees C, and after a temperature shift from 4 degrees to 37 degrees C elution of pre-adsorbed virus and accumulation of free N-acetyl-neuraminic acid (NANA) split from RBC receptors as a result of neuraminidase (Nase) activity was detected. In the case of high multiplicity of adsorption the elution was very fast (complete elution within 5 minutes) for all the strains irrespective of their virulence. Although physical saturation of RBC surface with the adsorbed virus was not achieved, a certain minimal (strain-specific) amount of the pre adsorbed virus which splits a maximally possible (for a given strain) quantity of the NANA was found (a state of "enzymatic saturation"). Below a certain low multiplicity of adsorption elution was delayed for about 20-30 minutes while the accumulation of the split NANA began immediately after the temperature shift. This phenomenon was interpreted as a result of "crawling" of the adsorbed virions upon the RBC surface followed by "browsing" of RBC receptors and liberation of NANA. Thus, the Nase activity of the attached virus ("in situ Nase activity") is a factor providing both elution and "crawling" of the virus (depending on the multiplicity of adsorption). The in situ Nase activity of all the strains used was determined quantitatively by (1) parameters of enzymatic kinetics (Vmax, Km and Km/Vmax) and (2) parameters of enzymatic efficiency related to a certain quantity of the adsorbed virus, namely, per amount of: a) "crawling" virus, b) that providing "enzymatic saturation", and c) that equal to Km. Computation of these parameters revealed inverse correlation between the in situ Nase activity and the strain virulence. Thus, these indications can be in vitro markers of the in vivo virulence. PMID- 4026584 TI - Recent H1N1 viruses (A/USSR/90/77, A/Fiji/15899/83, A/Firenze/13/83) replicate poorly in ferret bronchial epithelium. Brief report. AB - Three recent wild-type H1N1 influenza virus isolates (A/USSR/90/77, A/Fiji/15899/83 and A/Firenze/13/83) replicated poorly in organ cultures of ferret bronchial tissue compared with the replication of an H3N2 wild-type virus (A/England/939/69). All four viruses replicated well in nasal turbinate tissue. Examination of one H1N1 virus (A/USSR/90/77) in vivo showed heavy infection in the upper respiratory tract of ferrets but little in the lower respiratory tract. These results raise the possibility that the mildness of human influenza arising from the H1N1 strains may be due to lack of capacity to attack the lower respiratory tract as well as the presence of antibody in previously exposed persons. PMID- 4026583 TI - Optimisation of conditions for infection of isolated potato protoplasts with potato virus X. AB - Conditions for the reproducible infection of potato protoplasts with PVX were determined. Successful virus infection was achieved when potato protoplasts at a concentration of 3 X 10(5) cells/ml were incubated with 20 micrograms/ml PVX and 2 micrograms/ml Poly-L-ornithine (MW 100,000) for 15 minutes at 0 degrees C. Numbers of protoplasts infected varied between 30 and 50 per cent. Preincubation of PVX with PLO for a minimum of 10 minutes was essential for good infection. The type and molecular weight of polycation used had a major effect on virus infection. PLO at 100,000 MW was the most efficient. PMID- 4026585 TI - [The predominant site of airway obstruction in late asthmatic response (LAR)]. PMID- 4026586 TI - [Secretory IgA in immunological diseases of infants and children. Part II. Salivary s-IgA levels in patients with bronchial asthma]. PMID- 4026587 TI - [Cell membrane dynamics and intracellular fluidity of inflammatory cells induced by FMLP and PHA]. PMID- 4026588 TI - [Features of the innervation of fascia and their microcirculatory bed in the rat]. AB - By means of silver impregnation, methylene blue staining and using glyoxylic acid, the neural apparatus of the muscle fasciae in the shoulder girdle and back and their microcirculatory bed have been revealed in laboratory white rats. An uneven concentration of neuronal terminals makes the base of neurotissue interactions of the muscle fasciae of the shoulder girdle and the back of the rats. Only a small part of microvessels possesses neural elements. The fasciae and their microvessels are innervated both by sensitive and sympathetic neural fibers and their endings; they differ from each other morphologically and histochemically. The rat fasciae are useful objects for vital observations for behaviour both of the vascular nerves and the avascular areas. PMID- 4026589 TI - [Age and changes in the nerve supply of the superior and inferior venae cavae in man]. AB - The superior and inferior venae cavae have been studied in 51 human being at various age, beginning from newborns using histochemical methods. After birth concentration of neural plexuses in the venae cavae increases up to the period of puberty, and then after 40years of age, certain rarefication of adrenergic and then cholinergic neural plexuses is noted. Choline- and adrenergic innervation is revealed in myocardial fibers penetrating the walls of the superior and inferior venae cavae. PMID- 4026590 TI - [Features of the angioarchitectonics of the papillary muscles and the chordae tendineae of the human heart]. AB - In persons of mature, elderly and old age vascularization of the papillary muscles and tendinous chordae in the right and left cardiac ventricles has been studied depending on peculiarities of their structure and sources of their blood supply using injection, macro-microscopical, roentgenoangiographic methods, and silver nitrate impregnation. Certain data concerning the distribution zones in the papillary muscles of the coronary artery branches at various types of the cardiac blood supply are presented. Angioarchitectonics of the papillary muscles are described along their whole extention--in the basal area, in the middle part and at the apex. Architectonic peculiarities of the blood vessels in the muscular tendinous part of the papillary muscles and in some tendinous chordae are described. PMID- 4026591 TI - [Roentgeno-anatomy of the gastroduodenal artery]. AB - For the first time the data on clinical roentgenoanatomy of the functioning gastroduodenal artery and its branches are presented. It is based on analysis of vital angiograms performed in 607 persons (376 men and 213 women), in standard frontal and lateral projections. Certain roentgenological signs are described; they make it possible to distinguish the arteries from other vessels in the area. The data on topic position of the beginning of the arteries in regard to the vertebral column, depending on the sex of the examined persons, on direction, dimentions of the arteries, on their branches and on the character of their branching off are revealed. The data obtained could be useful in every day clinical practice of roenrgenoangiological rooms at making diagnosis and catheterization treatment of patients suffering from some pathology in the pancreatic-duodenal zone. PMID- 4026592 TI - [Interconversion of spiral D- and L-enantiomorphs of vascular muscles]. AB - Possibilities of mutual transformation of the right coiled enantiomorphs of the smooth muscle elements in the vascular walls into the left ones and vice versa have been studied. The circular smooth muscle cells make the base of similar transformation. They are coiled in one plane and connected by their ends with longitudinally situating cells. When the longitudinal cells contractile at both sides, the circular cells, stretching along the longitudinal axis of the vessel, arrange on the cylinder surface in the form of the right or left spirals. Their transformation into one another is reached by means of contracting the profile element at one or other side of the point where the circular element is fixed. The common regularity of this interreorganization is transition across the right left form of the Archimedean spiral. Similar enantiomorphism of mutual reorganization is considered in the model and determined as a reaction to gravitational-heat effect, contributing to better movement of the liquid biological medium along the blood vessel canals. PMID- 4026593 TI - [Morphofunctional features of different divisions of the microcirculatory bed of jejunal villi in the white rat]. AB - By means of injecting the vessels with vegetative peroxidase, scanning electron microscopy of corrosive preparations, biomicroscopy, transmissive electron microscopy and in serial semithin sections, spatial organization of the blood microcirculatory bed of the villus in the white rat jejunum has been studied and identification of various microvascular segments has been made. Increasing dimentions of the villus result only in multiplication of the outflow and inflow pathways of blood, while the number of the marginal capillary-distributers remains unchanged--one along each lateral part of the villus. The cause of this regularity should be sought in certain requirements to orientation of transport processes in the villose stroma and, first of all, in the conditions of the hemato-lymphatic transference at adaptation. PMID- 4026594 TI - [Cortico-nigral projections in the cat]. AB - Using the methods of retrograde axonal transport of horseradish peroxidase and silver impregnation of degenerating axons, certain data have been obtained demonstrating that frontal, motor, orbital, insular and limbic fields of the cortex serve as sources of afferent fibers for the compact zone of the substantia nigra. The lateral zone gets projections from the same cortical areas (besides the limbic one) as the compact part and, in addition, from the parietal associative, acoustic and visual areas. PMID- 4026595 TI - [Changes in the structure and cell composition of the thymus as a result of dosed physical loads]. AB - By means of histological and morphometrical methods normal age involution of the thymus has been studied, as well as its changes under conditions of dosed physical loadings. The experiment has been performed in 92 non-inbred white male rats. At adaptation of the organism to the loadings, involution of the gland decelerates, and at an insufficient adaptation--accelerates. This is, probably, the cause of decreasing protective forces of the organism. PMID- 4026596 TI - [Circulation time and dynamics of 3H-thymidine incorporation into DNA at various stages of chick embryo development]. AB - The most adequate method for carrying out radioautographic investigation on proliferation in the chorioallantoic tissues and in the chick embryo proper is dropping 3H-thymidine on the membrane under the shell in the area where the chorioallantois grows under. Using the application method, the radioautographic analysis of proliferation could be performed by the saturation method. PMID- 4026597 TI - [Formation of myoblasts after injuries to skeletal muscle tissue]. AB - The musculus masseter and the tongue in 75 mature rats have been injured by means of a scalpel, carbonate laser ray and ethanol administration. The regeneration process has been studied light and electron microscopically. Myosatellites that are constantly revealed in the skeletal muscle tissue, are the main source of myoblast formation under all the types of the muscle injury. When laser ray and ethanol are applied, myoblasts are also formed by means of segregation of the nucleo-sarcoplasmic territories of the muscle fiber. PMID- 4026598 TI - [Pubertal growth spurt in the thickness of the bones of the human cranium]. AB - Frontal saw-cuts of 60 human cranial fornices (age 1-21 years) served as the material for the investigation. By means of the microscope MBC-2 thickness of the bones was measured. The age changes of the bone thickness in the cranial fornix are approximated by the function of asymptotic growth TK' = 5.3-3.5 X 10(-0.14(X 1) (mm), where X = 1.2,..., 8 and logistic function TK' = 1/(1 + 10(11.4 - 0.74X) +4.93 (mm), where X = 8.9,..., 21 (years). Thus the bone thickness of the cranial fornix undergoes the pubertal spurt of growth, when the maximal rate in increasing thickness is noted between 15 and 16 years of age. This phenomenon should determine certain increase in dimentions of the skull during the pubertal period. PMID- 4026599 TI - [Chamber for studying microcirculation in muscles]. PMID- 4026600 TI - [Experience in optimizing the teaching of histology]. PMID- 4026601 TI - Recent developments in the diagnosis and treatment of myocarditis. PMID- 4026602 TI - Fetal movement--its use for fetal assessment. PMID- 4026603 TI - Some thoughts on books, journals, electronic publications, libraries and librarians. PMID- 4026604 TI - Does Alzheimer's disease represent an exaggeration of normal aging? PMID- 4026606 TI - Familial amyotrophic chorea with acanthocytosis. New clinical and laboratory investigations. AB - A 46-year-old man, the son of normal nonconsanguinous parents, had a rare progressive neurological illness that began in midlife and was characterized by seizures, buccolingual dyskinesia, orofacial tics, choreiform movements, areflexia, and neurogenic muscle atrophy. Acanthocytosis was present. The serum creatine kinase level was elevated and normobetalipoproteinemia was noted. A brother had a similar disorder. These clinical and laboratory characteristics are consistent with those of previously reported cases of neuroacanthocytosis, ie, familial amyotrophic chorea with acanthocytosis (FACWA). Features not previously reported in cases of FACWA and noted in our index patient are as follows: an increased level of free sialic acid was detected in the serum; haloperidol administered in high doses decreased the orofacial tics; absence of the McLeod blood group phenotype was noted; and Hispanic-Puerto Rican ancestry was documented. PMID- 4026605 TI - Severe dementia. Prevalence and clinical features in a biracial US population. AB - The purpose of this investigation was to document the prevalence of severe dementia among different racial groups residing in the same community--Copiah County, Mississippi. Both household and institutionalized populations were included. For either sex, the prevalence ratios of all severe dementia and clinically diagnosed severe senile dementia of the Alzheimer's type were at least as large among blacks as among whites. For either race, the corresponding prevalence ratios were greater in females. For each race and sex, the corresponding prevalence ratios increased with advancing age. Finally, in the population studied, approximately 1% of individuals 40 years old or older had severe dementia. This figure increased to 7% for individuals 80 years old or older. PMID- 4026607 TI - Olivopontocerebellar atrophy with dementia, blindness, and chorea. Response to baclofen. AB - Olivopontocerebellar atrophy is a hereditary disorder that has variable clinical manifestations. Five types have been described, as well as a sixth that contains sporadic cases. This report describes a family with three affected members who demonstrate a composite of types III and V. Their features include progressive spasticity, ataxia, dementia, visual loss with retinal pigmentation, dysarthria, ophthalmoplegia, and chorea. This family might represent an additional category of the disease. In the two family members who developed chorea, baclofen resulted in marked improvement with abolition of the choreiform movements. Response has been sustained for several years in the mother and for eight months in the daughter. Neither has experienced any return of chorea while receiving treatment. When attempts were made to discontinue baclofen, choreiform movements returned promptly and with their original severity. Baclofen, a gamma-aminobutyric acid analogue, may be useful in the treatment of other forms of chorea as well. PMID- 4026608 TI - The flight of colors test in multiple sclerosis. AB - Flight of colors (FOC), the rapidly changing series of colored afterimages perceived when a bright light briefly strikes the eye, is impaired or absent in patients with lesions affecting central visual fields, especially optic neuropathies (ONs). The effectiveness of a bedside test of FOC using a pocket flashlight was compared with that of pattern-reversal visual evoked responses (PRVERs) in examining 74 subjects): 20 controls, seven patients with ON not due to multiple sclerosis (MS), 26 patients with MS, and 21 patients with possible MS and no clinical ON. The FOC test correctly identified 95 of 99 normal eyes and 45 of 49 eyes with ON, and accurately diagnosed 140 (95%) of 148 eyes overall. In 84 eyes examined by PRVER and FOC, the results agreed in 73 cases (87%), including those of subclinical ON. PMID- 4026609 TI - Computed tomographic and postmortem study of a nonhemorrhagic thalamic infarction. AB - A 70-year-old man had a stroke and became unconscious. High-resolution computed tomography (CT) with 5-mm cuts disclosed bilateral thalamic infarctions, larger on the left than the right. He died one week later, and a postmortem examination was performed. By plotting the CT on templates constructed to show the different vascular territories of the thalamus, the infarctions were predicted to be in the territories of the interpeduncular profunda arteries. Comparing sagittal reconstructions to the Schaltenbrand and Wahren atlas, the following thalamic nuclei were thought to be involved: dorsomedial, parafascicular, and centrum medianum bilaterally; and reticular, ventroanterior, and ventrolateral on the left. Pathologic study confirmed these findings. We believe that it is possible to predict the vascular territory of thalamic infarctions by plotting the CT on templates showing the different vascular territories of the thalamus. Sagittal reconstructions of CT scans also permit the determination of thalamic nuclei involved in a lesion. PMID- 4026610 TI - Auditory brain-stem potentials with unilateral pontine hemorrhage. AB - Although there have been extensive anatomical and physiological studies in animals, the actual neural sources, or even the laterality, of some components of auditory brain-stem evoked potentials in humans are uncertain. We studied these responses in a 56-year-old patient who had a clearly demarcated pontine hemorrhage on the right side. The patient was somnolent, with dense left hemiplegia and signs of involvement of right cranial nerves V, VI, and VII. Stimulation of the left ear (ie, contralateral to the lesion) evoked a normal series of waves with clearly resolved positive components peaking at 2.0, 3.3, 4.8 (wave IV), and 6.0 ms (wave V). Stimulation of the right ear (ie, ipsilateral to the lesion) evoked only waves I, III, and IV. These results suggest that a pathway ipsilateral to the stimulated ear is necessary and sufficient for generation of auditory wave V and that wave IV is generated in bilateral pathways. PMID- 4026611 TI - Absence of the septum pellucidum. Overlapping clinical syndromes. AB - A patient with absence of the septum pellucidum, optic hypoplasia, congenital nystagmus, hemiatrophy, and seizures fulfilled clinical and radiological criteria for diagnosis of both septo-optic dysplasia and the syndrome of absent septum pellucidum with porencephalies. The anatomical and clinical similarities between these two syndromes suggest a common embryological basis. Their simultaneous presence in this case further supports this explanation. Clinically mild forms of both septo-optic dysplasia and the syndrome of absent septum pellucidum with porencephalies are now detected with the aid of computed tomographic scanning in patients with unexplained hemiatrophy, congenital nystagmus, seizures, and short stature. PMID- 4026612 TI - Nonconvulsive status epilepticus. Ictal confusion in later life. AB - In 11 patients without histories of absence seizures, acute prolonged confusion and/or prominent psychiatric manifestations occurred between the ages of 42 and 76 years, and were accompanied by 1 to 2.5-Hz generalized spike-wave or multiple spike-wave discharges in the EEGs. The patients were successfully treated with intravenously administered diazepam followed by orally administered phenytoin sodium and/or phenobarbital. The ictal confusion in later life seems to be an entity distinct from the typical petit mal status of early onset. PMID- 4026613 TI - Intra-blood-brain barrier IgG synthesis in cerebral cysticercosis. AB - Patients with central nervous system cysticercosis show elevated binding of cerebrospinal fluid (CSF) IgG to homogenized cysticercus. To determine whether any of the CSF IgG was the result of de novo intra-blood-brain barrier (BBB) synthesis, CSF and serum samples from six patients were examined for elevated rate of synthesis and oligoclonal bands. Five of the six patients had increased intra-BBB IgG synthesis rate and four of these patients also had oligoclonal IgG bands present in the CSF that were absent in the serum. These results demonstrate intra-BBB IgG synthesis similar to that observed in other infectious and inflammatory diseases of the central nervous system. PMID- 4026614 TI - Alternate-day clonazepam treatment of intractable seizures. AB - Several investigations have demonstrated a reduction in benzodiazepine receptor binding after long-term exposure to this class of drugs. Such receptor alterations may contribute to the decreased efficacy of benzodiazepines in the management of convulsive disorders. To minimize receptor alterations, several patients with intractable seizures received alternate-day clonazepam therapy, resulting in improved seizure control. The favorable clinical responses suggest that alternative methods of benzodiazepine administration may circumvent receptor subsensitivity resulting from prolonged drug treatment. PMID- 4026615 TI - Electroencephalographic abnormalities in children with congenital heart disease. AB - Ninety-eight consecutive patients with clinically suspected congenital heart disease were prospectively studied with electroencephalographic (EEG) recordings before cardiac catheterization. Twenty-five patients had abnormal EEGs. Fifty five patients had acyanotic heart disease and normal neurologic examination results, of whom 15 had abnormal EEGs. Thirteen had spikes or spike and wave discharges and two had mildly abnormal EEGs. Twenty-seven patients had cyanotic heart disease and normal neurologic examination results, of whom four had abnormal EEGs. Seven patients (8%) had abnormal neurologic examination results, of whom four had abnormal EEGs. There was a higher incidence of seizures with increasing age. Based on their medical history two children with acyanotic heart disease had had seizures without EEG abnormalities. Five children with normal catheterization findings and four children with Down's syndrome (two with abnormal EEGs) were excluded from the total of 98. These findings suggest that subclinical nervous system involvement may occur in congenital heart disease. PMID- 4026617 TI - Microsurgical management of trigeminal neuralgia. PMID- 4026616 TI - Reduction of polypharmacy in epileptic patients. AB - An attempt was made to reduce polypharmacy in 90 epileptic patients. All patients received their original drug regimen for at least six months and were followed up for a minimum of 16 months after reduction of polypharmacy. In 72 patients (80%), the average number of drugs administered was reduced from 2.75 to 1.49. In 39 of these (54%), a reduction was made to single drug therapy. Either no change or an improvement in seizure control was observed, and side effects decreased in many patients. In 18 patients (20%), medications could not be withdrawn. In nine of these, another drug was required for seizure control. In the remaining nine, more frequent seizures necessitated a return to the previous regimen. The critical variable predicting unsuccessful reduction of polypharmacy was the presence of multiple concurrent seizure types. PMID- 4026618 TI - Case against microvascular decompression in the treatment of trigeminal neuralgia. PMID- 4026619 TI - Embolic stroke complicating systemic lupus erythematosus. AB - Embolic stroke complicating systemic lupus erythematosus has been infrequently reported. We examined a 25-year-old woman who suddenly became hemiplegic. Two dimensional echocardiography identified a source of emboli. At cardiac surgery, friable thrombotic vegetations were found adhering to the mitral valve leaflets, left ventricular septal wall, and chordae tendineae. At autopsy several weeks later, careful pathologic examination of the heart failed to reveal evidence of thrombus formation or endocarditis. An embolus identical in appearance to the thrombotic vegetations described at cardiac surgery was found lodged in the left middle cerebral artery underlying the recent brain infarction. To our knowledge, this is the first report of embolic stroke in systemic lupus erythematosus caused by extensive cardiac thrombus formation in the absence of underlying endocarditis. PMID- 4026620 TI - Primary position upbeat nystagmus. Localizing value. PMID- 4026621 TI - Primary aberrant regeneration of the oculomotor nerve. Occurrence in a patient with abetalipoproteinemia. PMID- 4026622 TI - Childhood Guillain-Barre syndrome masquerading as a protracted pain syndrome. PMID- 4026623 TI - Involvement of the nervous system in hairy cell leukemia. PMID- 4026624 TI - Vertebrobasilar transient ischemic attacks. PMID- 4026625 TI - Personality disorder. PMID- 4026626 TI - Intrathecal interferon in the treatment of multiple sclerosis. Patient follow-up. AB - Follow-up observations on patients with multiple sclerosis who were treated with human fibroblast interferon (interferon beta) administered intrathecally for six months revealed a persisting beneficial effect in terms of a reduction in exacerbation rates. At the time of our last report in 1982, ten interferon beta recipients had shown a reduction in their mean exacerbation rate from 1.8/yr before the study to 0.2/yr during the study while ten control patients with multiple sclerosis showed no change in their rates during the study (0.69/yr) compared with before it (0.68/yr). That report was based on observations made for means of 1.9 years in the recipients and 1.6 years in the controls. The recipient patients have now been followed up for 4.4 years (mean) and their exacerbation rates have continued to decrease to a current mean level of 0.16/yr. The control patients were "crossed over" and began receiving interferon beta intrathecally after they had been in the study for two years without showing any change in their rate. During the 2.0 years since crossover they also have shown a reduction in exacerbation rate to a mean of 0.30/yr. The toxic side effects of interferon beta administered intrathecally were acceptable in view of the benefit achieved. Interferon was identified in the cerebrospinal fluid (but not the serum) of two patients prior to treatment, which is probably a manifestation of de novo production of interferon by the central nervous system in response to the multiple sclerosis disease process. PMID- 4026627 TI - Value of multiple sclerosis diagnostic criteria. 70 autopsy-confirmed cases. AB - We have evaluated the sensitivity of the most recent and most frequently used criteria for the diagnosis of definite multiple sclerosis by the retrospective study of the clinical files of 70 pathologically confirmed cases. For each case, the date of diagnosis was determined separately using different sets of criteria. The delay of diagnosis was then calculated. The diagnosis was made significantly earlier when certain criteria were used. This was more marked in the earlier years of the disease. We also found that cases of multiple sclerosis with progressive courses were diagnosed later than cases with other courses, whatever the criteria used. This was statistically significant only for a single criterion. PMID- 4026628 TI - The clinical spectrum of internuclear ophthalmoplegia in multiple sclerosis. AB - The eye movements of 100 patients with multiple sclerosis were examined clinically, including a saccade test. Thirty-four cases of internuclear ophthalmoplegia were found, of which 14 were bilateral and 20 were unilateral. Only three patients had full restriction of adduction, whereas 16 had no restriction at all. A continuous dissociated nystagmus was present in one patient only, while in 15 just a few beats of the abducting eye could be observed. In ten cases both restriction of adduction and dissociated nystagmus were lacking, and the diagnosis could only be made with the saccade test, which in all 34 patients showed a clearly visible disjunction of horizontal saccades. In 15 cases, infrared oculography was performed, which in all cases confirmed the clinical findings, and which in some cases disclosed an additional subclinical internuclear ophthalmoplegia on the opposite side. PMID- 4026629 TI - Magnetic resonance imaging and other techniques in the diagnosis of multiple sclerosis. AB - We evaluated 35 patients with multiple sclerosis (MS) by magnetic resonance imaging (MRI), cerebrospinal fluid (CSF) analysis, evoked potential testing, and computed tomographic (CT) scanning. As classified by the McAlpine et al and McDonald and Halliday criteria, 27 patients had definite MS, three had probable MS, and five had possible MS. All of the patients had multiple white matter lesions detectable by MRI that were evident predominantly in the periventricular areas but also in the cerebral or cerebellar white matter. The severity of the MRI abnormality, as judged by the number and size of the lesions, correlated with the likelihood of a positive CT scan but not with the duration of disease, the degree of disability, or positive CSF oligoclonal banding. Magnetic resonance imaging successfully demonstrated brain-stem lesions in 15 patients (none were seen on CT scans). Magnetic resonance imaging seems to be a sensitive indicator of MS lesions, but clinical assessment will continue to be crucial to the diagnosis of MS. PMID- 4026630 TI - Risk factors and concomitants of internal carotid artery occlusion or stenosis. A controlled study of 159 cases. AB - Presumed risk factors were studied in 159 patients with internal carotid artery (ICA) occlusion or stenosis. Smoking, family history of strokes, ischemic changes on electrocardiogram, and obesity were more frequent and blood pressure and plasma glucose levels were higher than in 159 sex- and age-matched controls. Blood pressure and plasma glucose levels were higher and smoking was more frequent in patients with occlusion than in those with stenosis. These points suggest that progression is related to some of the precursors of atherosclerosis. No difference was found between the patients with ICA disease and an age- and sex matched group who had coronary disease without carotid disease, except for diabetes, which was more frequent in ICA occlusion, and for family history, which corresponded to the site of atherosclerosis (carotid vs coronary). The constitutional basis may be the most important differential risk factor in ICA vs coronary disease. PMID- 4026631 TI - Morphometric effects of use and disuse on peripheral nerve. AB - Rat peripheral nerve was evaluated morphometrically following hemicordotomy, tenectomy, or both to assess the effects of disuse and hyperactivity on the peripheral nervous system. Hemicordotomy resulted in an increase in diameter of nerve fibers supplying both "fast" and "slow" skeletal muscles in hypoactive and hyperactive limbs. Nerve fiber atrophy occurred only in nerve to "fast" muscle following disuse induced by hemicordotomy and tenectomy. The possible role of "motor nerve growth factor" or altered axoplasmic flow in bringing about these morphologic changes in peripheral nerve is discussed. PMID- 4026632 TI - Matutinal vertigo. Clinical characteristics and possible management. AB - Vertigo frequently begins in the morning while the patient is in bed (matutinal vertigo). One hundred consecutive patients with vestibular disease were studied to assess the frequency and clinical characteristics of this temporal pattern. Forty-eight percent of the patients reported matutinal vertigo. The pattern can occur with central as well as peripheral disorders and is therefore not a localizing marker. It is most frequent with disorders in which positional features (vertigo and nystagmus) are prominent, and sleeping position appears to play a role in its production. It may be possible to prevent recurrent attacks by altering the patient's sleeping position. PMID- 4026633 TI - Atypical conduction aphasia. A disconnection syndrome. AB - Conduction aphasia was originally proposed to result from separation of the posterior language comprehension area and the anterior motor speech area of the left hemisphere. The arcuate fasciculus has been the most frequently suggested site of such a disconnection, but the syndrome has been reported in cases in which the abnormality involved the dominant Wernicke's area. This challenges the arcuate fasciculus theory, and it has been suggested that a cortical lesion, not a disconnection, is the crucial factor. Three new cases in which the lesion does not lie in the arcuate fasciculus are reported, two in left-handed patients with left temporoparietal lesions and one in a right-handed patient with a right temporoparietal infarct, a "crossed" aphasia. While atypical, these cases offer evidence that disconnection of the circuit linking language comprehension to motor speech output, not damage to a specific cortical region, underlies the syndrome of conduction aphasia. PMID- 4026635 TI - The geographic maldistribution of neurologists. One state's experience. PMID- 4026634 TI - Depression in patients referred to a dementia clinic. A three-year prospective study. AB - Of 225 patients referred to a dementia clinic, depression occurred in 31 (70%) of 44 patients not thought to be demented, six (24%) of 25 with cognitive impairment not severe enough to warrant the label dementia, and 24 (15%) of 156 with various forms of dementia, including 19 (19%) of 99 with Alzheimer-type dementia. Follow up over three years has shown that 16 (57%) of 28 of the depressed, nondemented patients went on to develop frank dementia. Thirteen of these 16 had some sign, often subtle, of organic neurologic disease. Depressed elderly patients with any of the following are at high risk to develop dementia: evidence of cerebrovascular, extrapyramidal, or spinocerebellar disease; a modified Hachinski ischemic score of 4 or greater; a Mental Status Questionnaire score under 8; a dementia behavior score of 7 or higher; or confusion on low doses of tricyclic antidepressants. Dementing illnesses can present as depression with relatively little cognitive impairment. PMID- 4026636 TI - Universal dissociated anesthesia due to bilateral brain-stem infarcts. AB - A 59-year-old man had loss of pin-prick and temperature sensation over his head, face, neck, trunk, and all extremities while light touch, vibration, joint position sense, and deep pain were preserved. This was the cumulative result of infarctions in the territories of the right superior cerebellar and left posterior inferior cerebellar arteries that occurred three years apart. To our knowledge, a syndrome of bilateral discrete interruption of spinothalamic tracts and of the spinal tracts of the trigeminal system in the brain stem has not been reported. Dissociated sensory loss enveloping the entire body accompanied by truncal and limb ataxia without weakness demonstrated a striking clinical picture. The preservation of deep somatic and visceral pain when cutaneous pain sensation was lost was another notable feature. We review the causes of widespread dissociated sensory loss and discuss the implications of the dissociation of deep from superficial pain. PMID- 4026638 TI - Hyaloid membrane vs posterior capsule as a protective barrier. PMID- 4026639 TI - Staphyloma formation as a complication of ultrasound treatment in glaucoma. PMID- 4026637 TI - Isolated cerebral phycomycosis presenting as focal encephalitis. AB - A patient with features of a focal encephalitis was found to have isolated cerebral phycomycosis. No risk factors for phycomycosis were present, and the diagnosis was made by brain biopsy. PMID- 4026640 TI - Low-tension glaucoma. Enigma and opportunity. PMID- 4026641 TI - Aphakic cystoid macular edema. A hypothesis. PMID- 4026642 TI - The risk of cerebrovascular and cardiovascular disease in patients with anterior ischemic optic neuropathy. AB - Of 217 patients in whom anterior ischemic optic neuropathy (AION) was diagnosed during the period from 1975 to 1985, verifiable medical information was obtained for 212 (98%). Over a median follow-up period of three years, no group of patients had an increased mortality rate over that of age-, sex-, and race matched controls; however, patients with "idiopathic" AION and patients with systemic hypertension who developed nonarteritic AION had a statistically significant increased risk of experiencing cerebrovascular events and myocardial infarctions compared with appropriately matched control groups. In view of the findings of our study, we suggest that patients with idiopathic AION and hypertensive patients who develop nonarteritic AION undergo a complete physical examination, cardiac evaluation, tests of carotid artery patency, and careful medical follow-up to attempt to prevent subsequent cerebrovascular or cardiovascular events. PMID- 4026643 TI - Cup-disc ratio and ischemic optic neuropathy. AB - Cup-disc ratios in the fellow eyes of 26 patients with unilateral, nonarteritic, anterior ischemic optic neuropathy were compared with the ratios in fellow eyes of 29 patients with unilateral idiopathic or demyelinative optic neuritis. The ratios in both groups were also compared with the ratios of a large group of normal subjects evaluated in a population survey. Observers measured the cup-disc ratio by viewing color stereophotographs. The cup-disc ratios of the fellow eyes of patients with anterior ischemic optic neuropathy were significantly smaller on average than were those of the fellow eyes of patients with optic neuritis and the normal subjects. Eyes with small cup-disc ratios may be more vulnerable to infarction than are eyes with large cup-disc ratios. PMID- 4026644 TI - Comparison of the optic nerve head in high- and low-tension glaucoma. AB - The optic nerves of 34 eyes of 34 patients with low-tension glaucoma were compared with those of 41 eyes of 41 patients with high-tension glaucoma. Mean intraocular pressure in the low-tension group was 16.9 +/- 0.7 mm Hg (mean +/- SEM) compared with 31.7 +/- 0.8 mm Hg in the high-tension group. Mean total visual field loss was not significantly different in the two groups, as determined by computerized threshold perimetry (OCTOPUS). The optic disc rim in low-tension eyes was significantly thinner than in high-tension eyes (P = .018); the largest difference occurred inferiorly and inferotemporally (P less than .001). The appearance of the optic nerve is useful to distinguish between these two subtypes of glaucoma and may be a more meaningful indicator than intraocular pressure. Our findings support the hypothesis that there are at least two different mechanisms for optic nerve damage in glaucoma. PMID- 4026646 TI - Optic nerve involvement in the acute retinal necrosis syndrome. AB - Two patients with acute retinal necrosis syndrome demonstrated enlarged computed tomographic images of the optic nerves, a previously undescribed manifestation of this disorder to the best of our knowledge. One patient, with the bilateral variety of this syndrome, demonstrated bilateral optic nerve enlargement and, in one eye, appeared to achieve visual improvement following an optic nerve sheath decompression. The second patient, with the unilateral variety of the syndrome, demonstrated only unilateral optic nerve enlargement. These observations suggest that the intraorbital optic nerve may be primarily or secondarily involved in the acute retinal necrosis syndrome. PMID- 4026645 TI - Decreased visual acuity from optic disc drusen. AB - Although visual field defects occur commonly from optic disc drusen, reduction in visual acuity is rare. We describe four patients with reduced visual acuity and one with visual field constriction to the point of legal blindness that resulted from optic disc drusen. The acute episodic and stepwise nature of visual loss in some of the cases in our series suggests a vascular mechanism. Reduced visual acuity from drusen remains a diagnosis of exclusion. It should be considered, however, when visual loss has been acute and nonprogressive or stepwise in a nerve fiber bundle distribution and when visual acuity is not reduced until visual field constriction is severe. PMID- 4026647 TI - Clinical experience with timolol in childhood glaucoma. AB - We studied 67 patients (100 eyes) with childhood glaucoma who were treated with timolol maleate. Thirty of these patients (40 eyes) did not require additional surgery or medications after being treated with timolol (follow-up, from six to 60 months). Thirty-one eyes (78%) in this group had a pressure drop; 18 eyes (45%) had a pressure drop of greater than 10 mm Hg. We conclude that timolol is effective in the treatment of pediatric glaucoma, although there is a need to be aware of its potential complications. PMID- 4026648 TI - Squamous cell carcinoma of the conjunctiva presenting with intraocular extension. AB - A 73-year-old man, when first seen clinically, had extensive intraocular invasion from a limbal squamous cell carcinoma after only a six-week history of symptoms. This mode of initial presentation is rare for this tumor type. PMID- 4026650 TI - Fundus lesions in malignant hypertension. I. A pathologic study of experimental hypertensive choroidopathy. AB - Experimental hypertensive choroidopathy was studied in 29 eyes from 15 monkeys in which accelerated renovascular systemic hypertension developed after a modified Goldblatt procedure. We followed up the animals from five days to 21 months to examine clinically and histopathologically the spectrum of the pathologic process. The pathologic features of hypertensive choroidopathy in our animals may be categorized into three phases: (1) Acute ischemic phase: The initial change in the choroidal vasculature was constriction of arterioles, which leads to focal necrosis of the choriocapillaris and the retinal pigment epithelium and focal subretinal exudate. (2) Chronic occlusive phase: Occlusive changes involving arteries, arterioles, and choriocapillaris occurred later. (3) Chronic reparative phase: With time, recanalization took place at all levels of the choroidal vasculature. The subretinal fluid was reabsorbed, leaving diffuse patchy depigmentation of the retinal pigment epithelium, which followed lobular arrangement of the choriocapillaris. Arteriolization of the choriocapillaris developed; this seems to be a defense mechanism to withstand the elevated systemic blood pressure. PMID- 4026649 TI - The histopathology of filamentary keratitis. AB - Filamentary keratitis is characterized by the presence of fine filaments of epithelium and mucus that are attached to the cornea. The exact pathogenesis of this entity has remained unclear. One reason has been the lack of pathologic specimens of corneas from patients with filamentary keratitis. We examined the corneas of a patient who had died while suffering from filamentary keratitis. Scattered groups of inflammatory cells and fibroblasts were present just below the basal epithelium. It seemed that these cells had disrupted the epithelial basement membrane and Bowman's layer. To our knowledge, this is the first postmortem analysis of a cornea in a patient with acute filamentary keratitis. These findings support the theory that filamentary keratitis results from damage to the basal epithelial cells, epithelial basement membrane, or both. PMID- 4026651 TI - Fundus lesions in malignant hypertension. II. A pathologic study of experimental hypertensive optic neuropathy. AB - Accelerated renovascular hypertension produces optic nerve changes ranging from optic disc edema to optic atrophy. To elucidate the pathogenesis of hypertensive optic neuropathy, the optic nerves from 12 monkeys (23 eyes) with accelerated renovascular systemic hypertension were studied by electron and light microscopy. Within 21 months, the animals demonstrated the entire spectrum of pathologic changes. In the optic nerves with optic disc edema, the prelaminar optic nerve exhibited vasoconstriction with subsequent axonal hydropic swelling, axolemma disruption, and glial swelling. In retrolaminar myelinated optic nerve, vasoconstriction was more severe, with endothelial swelling and pericytic degeneration resulting in intramyelinic vacuoles and glial swelling. Optic disc edema appeared to result from axonal hydropic swelling secondary to ischemic infarct, followed by loss of axons and gliosis in the prelaminar optic nerve. The retrolaminar myelinated nerve showed prominent microglial reaction and eventual atrophy of axons and glia. Ischemia seemed to play a major role in hypertensive optic neuropathy, which represents anterior ischemic optic neuropathy. PMID- 4026652 TI - Ocular signs in thiamine-deficient monkeys and in Wernicke's disease in humans. AB - Thiamine deficiency in the monkey is the animal counterpart of Wernicke's disease in humans. In the present study, thiamine deficiency was induced in 11 monkeys while three monkeys were given paired feedings supplemented by thiamine hydrochloride and three monkeys were maintained on regular chow. The typical clinical symptoms were apathy, inattention to peripheral stimuli, ataxia, ptosis, mydriasis progressing to pupillary areflexia, nystagmus, and ophthalmoparesis progressing to total ophthalmoplegia. With thiamine treatment, recovery was prompt and complete in mild to moderate cases but delayed and incomplete in severe cases. The animals were killed six or more months after discontinuance of the experiments to determine the chronic effects of treated thiamine deficiency. The significant abnormalities in the brain stem were symmetric gliosis and neuronal loss in the inferior colliculi, the regions of the third and sixth nerve nuclei, and the medial vestibular nuclei. White matter was characteristically spared. With the exception of the inferior colliculi, the target sites for neuropathologic changes were the centers for ocular motor control. PMID- 4026653 TI - Pediatric dacryocystorhinostomy. AB - Dacryocystorhinostomy (DCR) often has uncertain results in the pediatric age group. Poorly defined and rapidly changing anatomy, along with a tendency toward vigorous growth of scar tissue, may alter surgical results. We report our experience with 29 primary pediatric dacryocystorhinostomies and five reoperations. Strict attention to surgical anatomy allows attainment of success results (83%) comparable with those in adults in both traumatic and nontraumatic cases. Our results, surgical technique, and evaluation of failures are discussed. Meticulous suturing of anterior and posterior flaps is not necessary for good surgical results. Dacryocystorhinostomy is a successful therapeutic modality in childhood dacryostenosis with chronic dacryocystitis when medical therapy, probing, and silicone intubation have been unsuccessful. PMID- 4026654 TI - A modified glass tube for conjunctivodacryocystorhinostomy. AB - The standard glass tube used with a conjunctivodacryocystorhinostomy is subject to spontaneous displacement. Either internal displacement into the surgically created passageway or external displacement and loss are possible. We have modified the tube by adding a flange 4 to 6 mm from the tube's top. This anchors the tube and significantly reduces postoperative tube mobility. Many procedures that would otherwise fail can be salvaged by using this new tube. PMID- 4026655 TI - Treatment of Meniere's disease by intratympanic injection with lidocaine. AB - Intratympanic injection of lidocaine hydrochloride was used to alleviate distressing symptoms of tinnitus and vertigo in 28 patients with Meniere's disease. Of the 28 patients, 82% found an immediate improvement in vertigo, and there was an improvement in tinnitus in 67.8%. There was no change in complaints of tinnitus or vertigo in five patients with Meniere's disease who were each injected with a similar amount of saline into the middle ear, and who acted as a control group. An intratympanic injection of lidocaine alleviated the disabling symptoms of tinnitus and vertigo in some of the patients with Meniere's disease who had not reacted well to medical treatment. The procedure is without the hazards of the intravenous injection of lidocaine, and can be done by every otologist, even in clinic practice. PMID- 4026656 TI - Meniere's disease (syndrome?). PMID- 4026657 TI - Three-dimensional reconstruction of the cochlear nuclear complex in humans. AB - For accurate physical three-dimensional reconstruction of the cochlear nuclear complex (CN), we used light microscopy to analyze the CN boundaries, cell types, and myelinated nerve bundles and transferred traced contours from enlarged photographs of serial sections onto acrylic plates. We produced two models, one demonstrating the CN in relation to the brain stem and the other showing the CN completely dissected out of the brain stem. The models localized the CN boundaries on the brain-stem surface and revealed topographic characteristics of the CN and a part of the eighth nerve adjacent to the brain stem. The major parts of the CN, namely, the ventral and dorsal cochlear nuclei, are located mainly within the lateral recess. The models produced are currently used in our institution to determine the optimal surgical and electrophysiologic approach to the CN. PMID- 4026658 TI - The hospital-based helicopter. A threat to hearing? AB - Use of hospital-based helicopters for emergency medical transport has increased greatly over the past two years. We evaluated the associated noise exposure of pilots, aircrew, and transported patients by comparing a noise intensity-duration profile for the above groups to Occupational Safety and Health Administration standards for noise exposure. The duration of exposure varied from 0.51 to 2.33 hours per day and the noise intensity from 85 to 90 dB (A). The intensities were lower than previously reported in the literature. We conclude that noise protection and hearing conservation programs are not required for most civilian rotorcraft medical transport programs. PMID- 4026659 TI - Surgery in elderly patients with chronic otitis media. AB - The results of surgery in 75 ears in patients over 60 years of age affected by chronic otitis media were compared with the results of surgery in 693 ears in patients under 60 years of age affected by chronic otitis media. Results in the elderly patients were found to be as good as those in the younger patients. No severe complications of surgery occurred in the patients over 60 years of age. The authors recommend that surgery should be undertaken on ears of elderly patients affected by chronic otitis media on the basis of the same indications as in younger patients. PMID- 4026660 TI - Osteogenesis in vascularized periosteum. Interactions with underlying bone. AB - This study is the first in a series of experiments undertaken to obtain basic information regarding the behavior of vascularized periosteum. Ten adult dogs were used and in each animal costal periosteum was alternatively placed in contact with normal (but previously detached) rib, and rib segments devitalized by autoclaving, decorticated, and isolated by means of a Silastic wrap. Specimens were harvested at 10, 20, 40, and 70 days and were evaluated grossly, histopathologically, and by tetracycline hydrochloride fluorescence studies. Periosteum in contact with intact bone became osteogenic within 20 days. Periosteum in contact with autoclaved and decorticated bone also became osteogenic but at a slower rate. Isolated periosteum failed to produce bone. These findings indicate that osteogenesis in transferred periosteum depends not only on maintenance of its vascular supply but also on its proximity to viable bone and its ability to interact with the recipient surface. PMID- 4026661 TI - Skin wound approximation with new absorbable suture material. AB - A new rapid strength loss catgut suture material can be used for skin closures in wounds of the face and body. Seventy-six comparisons were made under controlled conditions between the new material and one formerly recommended. The new material was used in 588 other wounds as well. It is concluded that the new material is superior to the other in several important ways. PMID- 4026662 TI - A scale for evaluating results of rhinoplasty. AB - A system was developed to numerically grade noses before and after rhinoplasty. Based on the use of photographs, it permits objective assessment of the amount of improvement resulting from operation. By extension, it could be used to rate surgical proficiency. PMID- 4026663 TI - Combined functional oral rehabilitation after radical cancer surgery. AB - Formerly, patients requiring extensive reconstruction of the oral cavity and oropharynx after radical, ablative oncologic surgery faced the unhappy prospect of lengthy, multistaged repair to enjoy acceptable cosmesis and a functional oral cavity. The advent of the pectoralis major myocutaneous flap has made soft tissue, single-stage closure of large oral cavity and oropharyngeal defects a reality. Unfortunately and frequently, restoration of mucocutaneous continuity of the mouth does not result in acceptable function. Advances in the materials and design of prostheses suggested the combination of myocutaneous flap reconstruction and functional, prosthetic restoration as a method of returning the patient with head and neck cancer to a state of acceptable function and appearance soon after major resection. PMID- 4026664 TI - Cervical lymph node metastases. Incidence and implications of extracapsular carcinoma. AB - The incidence and prognostic significance of extracapsular spread (ECS) of tumor in cervical lymphatics was investigated. The surgical specimens from 349 patients treated for squamous cell carcinoma by radical neck dissection between 1978 and 1982 have been examined retrospectively. Follow-up data were available relative to recurrence rate, site of recurrence, and disease-free intervals. Fifty-nine percent of the patients with N1 cervical metastases had ECS. Patients were classified according to the histopathologic findings in the radical neck dissection specimens. The three groups identified were patients with normal nodes, patients with no ECS, and patients with ECS. The histopathologic evidence of ECS was associated with a statistically significant reduction in survival when compared with patients without ECS. The disease-free interval between treatment and the development of recurrent disease was shorter for patients with ECS than for patients with no ECS. PMID- 4026665 TI - Defective monocyte chemotaxis in patients with epidermoid tumors of the head and neck. AB - The function of the immune surveillance system has been studied extensively in patients with neoplastic disease. Defective monocyte chemotaxis has been demonstrated in a variety of neoplastic conditions. We have assayed chemotaxis in monocytic and polymorphonuclear leukocytes taken from patients with epidermoid tumors of the head and neck. Multiwell chemotaxis chambers and the chemoattractant, formyl-methionyl-leucyl-phenylalanine, were used. Polymorphonuclear leukocytes responded normally, but monocytes from all tumor patients studied displayed marked reductions in random migration (86% inhibition) and in chemotaxis (77% inhibition) toward formylpeptide. PMID- 4026666 TI - Medullary space involvement in laryngeal carcinoma. Computed tomographic demonstration. AB - The identification of cartilage involvement in laryngeal carcinoma implies advanced stage T4 disease. Although computed tomography (CT) provides the most accurate method of assessing these cartilages, subtle cartilage invasion may go undetected. The major pitfall in detecting tumor involvement is the incomplete calcification of these structures, which may simulate cartilage destruction. High resolution CT now allows the evaluation of the medullary space of these cartilages. The CT finding of abnormal soft tissue in the central medullary space in addition to a focal cortical defect allows the confident diagnosis of cartilage involvement. PMID- 4026667 TI - Facial nerve palsy associated with Warthin's tumor. AB - A solid parotid mass and an ipsilateral facial weakness is nearly pathognomonic for a malignant parotid neoplasm. There are only a few documented cases in the world's literature of nonmalignant parotid lesions causing facial paralysis. A case is presented of a Warthin's tumor causing a facial palsy. Extensive areas of necrosis, inflammation, and fibrosis surrounding branches of the facial nerve may have accounted for the facial palsy. PMID- 4026668 TI - Clostridium difficile colitis following head and neck surgery. Report of cases. AB - Clostridium difficile, a toxin-producing, gram-positive anaerobe, has been implicated as the causative agent of pseudomembranous colitis, an acute inflammatory bowel disease that generally occurs in association with antimicrobial therapy. This subject has received extensive review in the general surgical, medical, and pediatric literature but has not been specifically addressed in the literature of our specialty. We present the report of four recent cases, including one that progressed to the clinical picture of peritonitis and toxin megacolon. The literature is reviewed regarding presentation, diagnosis, and treatment of C difficile colitis. Familiarity with this disease process may minimize morbidity and prevent disastrous complications following major head and neck surgery. PMID- 4026669 TI - Acquired immune deficiency syndrome--related lymphadenopathies presenting in the salivary gland lymph nodes. AB - Homosexual males at risk for acquired immune deficiency syndrome (AIDS) frequently present with peripheral lymphadenopathies that precede the opportunistic infections and neoplasias of this disease. Two homosexual males had enlarged salivary glands due to lymphadenopathies initially affecting intraparotid and perisubmaxillary gland lymph nodes. Both the hyperplastic and the atrophic histologic patterns of AIDS-related lymphadenopathies were observed in the lymph nodes. Subsequently, the two patients developed lymphoma and opportunistic infections, respectively. The AIDS-related lymphadenopathy developing in salivary gland lymph nodes is an entity that should be considered in the differential diagnosis of salivary gland tumors. PMID- 4026670 TI - Facial palsy in Bannwarth's syndrome: a tick-borne spirochetosis. PMID- 4026671 TI - The twisted larynx: a clinical syndrome. PMID- 4026672 TI - Pathologic diagnosis: histoplasmosis of the tonsil. PMID- 4026673 TI - Functional endoscopic sinus surgery. Theory and diagnostic evaluation. AB - The keys to functional endoscopic sinus surgery are an understanding of the underlying mechanisms of paranasal sinus disease and the ability to diagnose the causes accurately. Previously unrecognized causes of recurrent acute sinusitis and of chronic sinus symptomatology can now be identified by careful diagnostic evaluation. Systematic nasal endoscopy and high-resolution computed tomographic imaging provide complementary diagnostic information that can allow for the recognition of problems not identifiable by other means. The ability to diagnose these problems and to correct them with functional endoscopic surgery heralds new possibilities in the field. PMID- 4026674 TI - Diagnosis and management of obstructive sleep apnea. A multidisciplinary approach. AB - Snoring has been shown to be the primary sign of a potentially serious medical condition, ie, obstructive sleep apnea (OSA). Traditionally, the otolaryngologist has been the primary medical resource for patients with snoring problems. However, until recently, little was known about the now-acknowledged serious complications of this phenomenon. Of the primary treatments for this condition, those most commonly utilized to date involve surgical procedures routinely performed by the otolaryngologist, ie, tracheostomy and uvulopalatopharyngoplasty. Thus, the practicing otolaryngologist has been thrust into the forefront in the diagnosis and management of OSA. Hence, it behooves the modern practitioner to be cognizant of the multidisciplinary approach to this problem. Herein, we review snoring as a medical problem, sleep laboratory studies of patients with OSA, and the interaction of multidisciplinary team members in the optimal management of this ubiquitous problem. PMID- 4026676 TI - Circulating immunocomplexes and laryngeal carcinoma. AB - Serum levels of circulating immunocomplexes (CIC) were studied in a group of 37 patients with laryngeal carcinoma using two polyethylene glycol-precipitation methods. The preoperative values of this group showed higher levels of CIC when compared with 140 normal controls. No correlation was noted between tumoral stage, oncotype, and serum levels of CIC. Previous studies have shown that the status of several different types of human tumors can be monitored by serial determinations of levels of CIC. We believe that this technique can be used to evaluate the efficacy of therapy and to detect the recurrence of laryngeal carcinoma. PMID- 4026675 TI - The role of endoscopy in evaluating patients with head and neck cancer. A multi institutional prospective study. AB - In a prospective multi-institutional study of 384 patients undergoing endoscopy, an 8.9% incidence of second primary neoplasms was discovered simultaneously in the lung (3.3%), esophagus (1.8%), and other head and neck sites (3.6%). The endoscopy was the only source of detection of these tumors in 58% of cases. A trend indicates that flexible fiberoptic bronchoscopy was more effective than rigid bronchoscopy in discovering lung tumors (7.5% vs 2.3%). Nevertheless, the chest roentgenogram remains an important tool in the diagnosis of second primary lesions in the lung. Panendoscopy is safe, takes little time, and can add invaluable information concerning therapy in patients with head and neck cancers. PMID- 4026677 TI - Measurement of alternative blood flow in the porcine panniculus carnosus myocutaneous flap. AB - The dependence of a transposed myocutaneous flap on its own vascular pedicle for survival is time-related. The number of days required to establish effective sustaining perfusion from the periphery was assessed. Based on flap perfusion with associated vascular compression as monitored by the laser Doppler and dermofluorometer, adequate perfusion levels occurred at days 7 to 10 in the pig panniculus carnosus myocutaneous flap. It was established that all flaps will survive independent of the vascular pedicle when the laser Doppler readings are above 40 mV and the dermofluorometric readings are above 20%. The establishment of this baseline information now allows for the investigation of pharmacologic manipulation of the blood flow to diminish the duration of dependence on the transposed vascular pedicle. PMID- 4026678 TI - Otitis media at Canyon Day, Ariz. A 16-year follow-up in Apache Indians. AB - A 16-year follow-up survey of native Americans living in Canyon Day, Ariz, did not show improvement in the 9.3% rate of clinically significant otitis media. However, the manifestations were more benign, especially in children, and included the spectrum of otitis media. A genetically determined eustachian tube difference may explain the high rate of occurrence of otitis media in these Apache Indians. Improvements in living conditions and health care may explain the change to less severe manifestations. PMID- 4026679 TI - Auditory brain-stem response in determination of brain death. AB - A diagnosis of brain death requires evidence of irreversible destruction (or dysfunction) of neurons in the brain stem and cerebrum. The physical examination is not a valid index of brain integrity in patients who are drug-intoxicated or receiving therapeutic paralyzing agents or high-dose barbiturates. We evaluated the use of the auditory brain-stem response (ABR) as an ancillary test in the determination of brain death. A total of 100 combined ABR and nuclear cerebral blood flow studies were completed at bedside with 81 acute, severely brain injured adults. The ABR and cerebral blood flow outcomes were significantly correlated. We conclude that the ABR is a clinically feasible and useful procedure in the determination of brain death, especially in patients whose medical therapy compromises the neurologic examination. PMID- 4026680 TI - Congenital cholesteatoma of the petrous pyramid. AB - A 20-year follow-up was done on a patient with a large congenital cholesteatoma of the petrous apex. The patient was treated successfully with marsupialization through a radical mastoidectomy and sphenoid sinusotomy. Cranial computed tomography and magnetic resonance imaging demonstrated continued cholesteatoma growth. Bone-conduction thresholds remained normal despite replacement of the internal auditory canal by cholesteatoma matrix. The patient continues to have chronic otorrhea, but is otherwise asymptomatic. PMID- 4026681 TI - A mucocele of the submandibular gland. AB - We encountered an unusual case of a mucocele arising from the submandibular gland. Among the limited number of cystic salivary gland neoplasms reported in the literature, there have been no reports, to our knowledge, of a similar cystic lesion. The unique characteristics of this mass permitted definitive diagnosis by computed tomographic scanning. PMID- 4026683 TI - Reconstruction of large nasal defects with a subcutaneous pedicle nasolabial flap. An underutilized technique. AB - The cosmetic repair and camouflage of large full-thickness defects of the nasal bridge and lower nasal skin can be an arduous task. The standard techniques of split- or full-thickness skin grafts provide for a poor color match and inadequate tissue mass, and other flap techniques do not have the versatility, tissue bulk, and ability to hide the donor site that the subcutaneous nasolabial pedicle flap does. This technique has versatility in treating larger lower nasal bridge defects. PMID- 4026682 TI - Autograft frontoplasty. A simple technique for correction of post-osteoplastic flap defects. AB - A rare but distressing complication of frontal embossment was managed after osteoplastic flap surgery. The technique is relatively simple and predictable, consisting of frontal bone autografts, bone pate, and Silastic sheeting. This technique may have potential application to other posttraumatic defects that require frontal contour restoration. PMID- 4026684 TI - Is there an auriculovagal reflex producing cardiac dysrhythmias? PMID- 4026685 TI - Management of patients with tinnitus. PMID- 4026686 TI - Pathologic quiz case 1. Hairy polyp. PMID- 4026687 TI - Pathologic quiz case 2. Antral choanal polyp. PMID- 4026688 TI - Investigations of serum testosterone levels in patients with laryngeal cancers. AB - Serum testosterone levels were determined by a radioimmunological method in 102 patients with laryngeal carcinoma and in a control group of 10 healthy men. All patients were examined before the initiation of any operative or radiation therapy and after termination of treatment. The testosterone levels in the cancer patients showed a tendency toward higher values when compared with a control group of healthy men. These results indicate that hormone preparations could be considered as part of the therapy of laryngeal carcinomas. PMID- 4026689 TI - Schneiderian papillomas of the nasal septum. AB - A case of Schneiderian papilloma of the nasal septum is presented. The condition is rare, as indicated by a review of previously published cases. The clinical course of the lesion suggests that it behaves like Schneiderian papillomas elsewhere in the nasal cavity and paranasal sinuses. The need for aggressive surgical management and careful follow-up is emphasized. PMID- 4026690 TI - Parotid gland hemorrhage as a complication of coumarin compound ingestion. AB - Bleeding in the salivary glands represents a very rare complication of oral anticoagulant therapy. Only one such case has been previously described in the submandibular glands. To the best of our knowledge, we document the first case of hemorrhage in the parotid gland following the ingestion of coumarin compounds. PMID- 4026691 TI - Hyperbaric oxygen therapy for acute acoustic trauma. AB - We conducted a study on the effect of hyperbaric oxygen therapy on 122 soldiers following acute acoustic trauma. The patients included in this study, after the effect of spontaneous recovery had largely been excluded, were randomly allocated to four treatment groups. The results of our studies show that hyperbaric oxygen therapy shortens the course of healing with respect to high-pitch perception dysacusis. The results of treatment after an observation period of 6 weeks is also more favorable when patients are treated with oxygen when compared to patients given infusions or vasoactive substances. Similarly, the use of hyperbaric oxygen therapy also reduces the frequency of relapse following discharge from hospital. In contrast, the vasoactive substance chosen in our studies (betahistine) failed to have a favorable effect on the course of healing. Our study has also shown that no method can compare with hyperbaric therapy in eliminating tinnitus following acoustic trauma. PMID- 4026692 TI - The growth rate of acoustic neuromas: a report of three cases. AB - Until the present time, only a few CT air-cisternographic studies have been done to define the growth rate of acoustic neuromas. By using this method of study, we were able to observe a slow growth rate fo acoustic neuromas in a 41- and a 50 year-old woman over periods of 6-10 months. In contrast, we were unable to find any increase in tumor size during a period of 22 months in a 70-year-old woman. PMID- 4026693 TI - Scanning electron microscopy of the human submandibular gland. AB - We examined human submandibular gland parenchyma by scanning electron microscopy after removal of connective tissue components by HCl hydrolysis. Stellate-shaped myoepithelial cells and basal infoldings were clearly seen, indicating active function of the gland. PMID- 4026694 TI - The formation of ultrastructural epithelial and subepithelial connective tissue changes in experimentally induced cholesteatomas in guinea pigs. AB - Histoacryl-induced cholesteatomas were produced in guinea pigs at the posterosuperior part of the external ear canal adjacent to the tympanic membrane. Semithin and ultrathin tissue sections were used to study primary formation of the cholesteatoma as well as the influence of the altered epithelium upon the bordering zone of connective tissue. Quantitative and qualitative tissue changes were analyzed by electron microscopy and showed degradation and new formation of collagen and activation of fibroblasts. Our findings are similar to those previously reported on human cholesteatomas and indicate that the bordering subepithelial tissue seems to be influenced through the basilar membrane. PMID- 4026695 TI - The effect of glycerol on cochlear function and ionic concentration. AB - The use of glycerol continues to be a popular clinical test for diagnosing reversible hearing loss in patients with Meniere's disease, although its mechanism of action remains obscure. The purpose of this investigation was to study experimentally the alterations in the ionic composition and function of the cochlea which occur following glycerol administration. Immediate decreases in inner ear pressure and increases in AP threshold were seen. Delayed decreases in the endocochlear potential with increases in inner ear electrolytes occurred. However, we were unable to find any substantial changes in inner ear oxygen concentrations. Our findings support the concept that the principal action of glycerol is in osmotic reduction of inner ear pressure. PMID- 4026696 TI - The effects of tympanic neurectomy and chorda tympanectomy on experimentally induced parotid duct fistulae in rabbits. AB - To study the effects of parasympathetic denervation on the secretory activity of parotid fistulae, polyethylene catheters were introduced bilaterally into the parotid main excretory ducts of 10 rabbits, followed by unilateral parasympathectomy performed by segmental resection of the tympanic plexus and the chorda tympani nerve. Although salivary flow from the fistulae of the denervated parotid glands stopped up to 8 days earlier than that from the healthy (control) glands, the effect of parasympathectomy was not strong enough to recommend this operation as the method of choice for the clinical inactivation of persistent parotid fistulae. PMID- 4026697 TI - Virus-like particles in human vestibular ganglion cells. AB - We found intracytoplasmic aggregates of virus-like particles in human vestibular ganglion cells. These particles were always observed in the peripheral area of the cytoplasm. Morphological characteristics of the cytoplasm are similar to those of other ganglion cells. The inclusion bodies are round and measure about 1.7 micron in maximum diameter. They consist of a porous convoluted dense material and virus-like particles. The overall diameter of 118 randomly selected particles varies from 36 nm to 73 nm, and the mean value is 53 nm. Most of the particles are spherical while a few possess a hexagonal or semicircular profile. The particles exhibit a double external membrane or vesiculated external layer. Most of the particles are empty. There are, however, some particles which show vesicular structures in their content. Although our present data are insufficient to determine these particles as viral, their hexagonal shape and size are similar to true virus. With these data in mind, we suggest that these particles might be a dormant form of virus and may possibly produce infectious disease in the inner ear. PMID- 4026698 TI - Immunological investigation and treatment of rhinitis and bronchial asthma. PMID- 4026699 TI - Hay fever, rhinitis and nasal polyps. PMID- 4026700 TI - Hay fever. PMID- 4026701 TI - Wood's light examination. PMID- 4026702 TI - A university teaching practice: can it teach, research and fulfil a normal service role? PMID- 4026703 TI - Where have all the babies gone? An infant care study. PMID- 4026704 TI - Anxiety disorders: Part 1. PMID- 4026705 TI - The ticket of entry. Authentic case histories from Australian general practice. PMID- 4026706 TI - The effects on children of parental separation and divorce. PMID- 4026708 TI - Some aspects of the management of angina. PMID- 4026707 TI - Cervical cancer and the Papanicolaou smear. PMID- 4026709 TI - Mortality and morbidity in adolescence. PMID- 4026710 TI - Doping in sport. PMID- 4026711 TI - Upper thoracic back pain. PMID- 4026712 TI - Evaluation of two C.T. scanners for dual energy applications. PMID- 4026713 TI - Application of the Monte Carlo technique to the study of radiation transport in a prompt gama in vivo neutron activation system. PMID- 4026714 TI - Quality assurance protocols for diagnostic x-ray equipment. Part 1: General radiographic units. PMID- 4026716 TI - Familial nephropathy in cocker spaniels. AB - A clinical diagnosis of chronic renal failure associated with nephron atrophy and fibrosis was made in 4 blue roan Cocker Spaniels. The lesion was considered to be the result of a primary glomerulopathy. All dogs were closely related. The findings were similar to those previously described for renal cortical hypoplasia. On the basis of the morphological findings and genetic characteristics, the use of the more appropriate term, familial nephropathy is encouraged. PMID- 4026715 TI - Some recent advances in nuclear magnetic resonance imaging. PMID- 4026717 TI - Pharyngeal lymphoid hyperplasia in Thoroughbred racehorses in training. AB - The prevalence of pharyngeal lymphoid hyperplasia in Thoroughbred racehorses in training was investigated using a fibre optic endoscope. Of the 70 horses examined, all but 8 showed evidence of pharyngeal lymphoid hyperplasia and the severity of the pharyngeal changes decreased with age. Two-year old horses had greater pharyngeal lymphoid hyperplasia (p less than 0.05) when compared to all other age groups. More horses (p less than 0.05) with Grade 3 or Grade 4 pharyngeal lymphoid hyperplasia experienced recent mild respiratory disease than did horses with Grade 2 or less pharyngeal lymphoid hyperplasia. None of the horses examined had a history of diminished racing performance although 30% had either Grade 3 or Grade 4 pharyngeal lymphoid hyperplasia. PMID- 4026718 TI - Pituitary tumour causing multiple endocrinopathies in a dog. AB - A 9-year-old male Boxer with signs of lethargy, weight gain, polyuria, polydipsia, eosinopaenia and lymphopaenia was diagnosed as having hyperadrenocorticism. Concurrent central diabetes insipidus was diagnosed using a water deprivation test and antidiuretic hormone response test. A contrast radiographic technique was used to outline a pituitary mass. A chromophobe adenoma and secondary hypothyroidism were found on post-mortem examination. PMID- 4026719 TI - Suspected monensin toxicosis in feedlot cattle. AB - Suspected monensin toxicosis was seen in feedlot cattle aged 6 to 9 months. Twenty cattle died following inclusion of monensin in the feed at 400g/tonne, which was 13 times the recommended level. The deaths occurred over 2 weeks. Clinical signs were inappetance, respiratory distress and sudden death. Post mortem features were those of right-sided heart failure and included dependent subcutaneous oedema, ascites, hydrothorax, and periancinar hepatocyte congestion and necrosis. However, in contrast to previous reports no myocardial necrosis was found, but focal skeletal muscle necrosis was observed. Additional findings were marked pulmonary oedema accompanied by fibrin and erythrocyte exudation into alveoli and interlobular lymphatics. From these findings it appears that monensin, as well as affecting both cardiac and skeletal muscle, has a primary effect on lung vasculature. PMID- 4026720 TI - Echinura uncinata infestation in mute swan cygnets (Cygnus olor). PMID- 4026721 TI - Haemonchus-free trichostrongylid illthrift in unweaned lambs in south eastern Queensland. PMID- 4026722 TI - Incidence of poisonings in dogs and cats in Melbourne. PMID- 4026723 TI - Mastitis in cows and polyarthritis and pneumonia in calves caused by Mycoplasma species bovine group 7. PMID- 4026724 TI - The prevalence of ovine brucellosis in cull Merino rams in western Australia. PMID- 4026726 TI - Epidemiological aspects of hyperlipaemia in ponies in south eastern Australia. PMID- 4026725 TI - Experiments with limestone supplemented cereal grain fed sheep. PMID- 4026727 TI - Eimeria canadensis in calves. PMID- 4026728 TI - Virus isolation from tracheal explant cultures and oropharyngeal swabs in attempts to detect persistent Newcastle disease virus infections in chickens. AB - Three-to-seven-week-old broiler-type chickens were inoculated with Newcastle disease virus (NDV) by eye-drop (ED) or intratracheally (IT), and virus isolation was attempted from oropharyngeal (oral) swabs and medium harvested from tracheal explant cultures (TEC). The TEC were maintained in screw-capped tissue-culture flasks for at least 1 month, and medium harvested at regular feeding times was assayed for NDV and NDV antibody. The earliest and latest sample times were 3 and 21 days after NDV inoculation. The three experiments done were: Expt. 1, infection of nonvaccinates with NDV strain La Sota; Expt. 2, infection of NDV vaccinates and nonvaccinates with NDV strain Largo; and Expt. 3, infection of NDV vaccinates and nonvaccinates with NDV wild-type strain Kansas-Manhattan (KM) and two temperature-sensitive (ts) clones derived by J. S. Youngner from the KM strain. All experiments yielded similar results. On day 3 postinoculation (PI), most chickens were shedding virus recoverable by oral swabs and detectable in harvests from TEC prepared on that day. On day 7 PI, there was a sharp reduction in the frequency of virus-positive oral swabs, but there was no decline in the frequency of virus-positive TEC. On day 14 PI or later, all oral swabs and TEC were virus-negative, except for one chicken in Expt. 3 that was oral-swab positive. There was no evidence of NDV persistence in the TEC of oral-swab negative chickens on or after day 14 PI. The results of these experiments are in contrast with previous reports of the detection of latent NDV by virus isolation from harvests of TEC prepared 18 or more days PI. The ts clones of strain KM used in Expt. 3 induced a markedly poorer antibody response and were shed for a shorter time than the KM parental virus. PMID- 4026729 TI - Divergent selection of chickens for antibody response to sheep erythrocytes: kinetics of primary and secondary immunizations. AB - Chicks from lines selectively bred for either high or low antibody response post primary immunization (PPI) to sheep erythrocytes (SRBC) and their reciprocal crosses were immunized intravenously with 0.1 ml of 0.25% SRBC antigen in Trials 1 and 3 and with 0.1 ml of 0.025%, 0.25%, or 25% SRBC antigen in Trial 2. All initial immunizations were made at 35 days of age, and 0.1 ml of 0.25% SRBC booster dose was given 24 days later. Results showed that (a) population differences appeared by day 4 PPI and persisted through day 24 PPI, (b) regardless of population, peak titers occurred at about the same time for primary and secondary immunizations, (c) dosage of antigen influenced differences among populations in antibody response to primary immunization, and (d) both selected lines had similar responses in 2-mercaptoethanol-sensitive and 2-mercaptoethanol resistant antibodies to primary but not secondary immunization. PMID- 4026730 TI - Paramyxovirus type 3 (PMV-3) in California turkeys: serologic study of PMV-3 antibody with an enzyme-linked immunosorbent assay. AB - An enzyme-linked immunosorbent assay (ELISA) was developed for detecting paramyxovirus type 3 (PMV-3) antibody. This test had a higher sensitivity than the hemagglutination-inhibition test, and no cross-reactivity with various paramyxoviruses or avian pathogens was detected when the sera were tested diluted 1:200. The incidence of PMV-3 infection in California was studied by testing 2037 turkey sera from 174 meat and breeder flocks for the presence of PMV-3 antibody using the ELISA. The age at which the infection occurs was around 5 to 8 weeks for meat flocks and 10 to 12 weeks for breeder flocks. Infection with the PMV-3, as determined serologically, was more frequent than manifested cases of disease, and 95.2% of the flocks aged over 11 weeks had PMV-3 antibody. No typical manifestations of PMV-3 disease (respiratory disease plus drop in egg production) were observed, probably because of the early infection which occurred before laying age. PMID- 4026732 TI - Transmission of Campylobacter jejuni by the housefly (Musca domestica). AB - Houseflies (Musca domestica) were infected with Campylobacter jejuni after being confined for 5 days in a Horsfall isolator containing 25-day-old chickens known to be fecal excretors of the organism. Contaminated flies, when subsequently transferred to a second unit, transmitted C. jejuni to specific-pathogen-free chickens. Allowing a sample of 32 houseflies to ingest C. jejuni in a liquid suspension resulted in recovery rates of 20% from the feet and ventral surface of the body and 70% from the viscera. These experiments demonstrated the potential role of flies in the dissemination of avian campylobacteriosis. PMID- 4026731 TI - The in vitro response of turkey lymphocytes to steroid hormones. AB - The in vitro mitogen response of whole blood turkey lymphocytes to various concentrations of steroid hormones was evaluated. Corticosterone (COS) at concentrations between 1 and 80 ng/ml significantly suppressed the proliferative response (3H-thymidine incorporation) to phytohemagglutinin (PHA) and concanavalin A (ConA). Non-mitogen-stimulated (NMS) cells were suppressed at concentrations of COS above 5 ng/ml. Progesterone significantly suppressed NMS cells at concentrations of 80 ng/ml, PHA-stimulated cells at concentrations of 500 ng/ml, and ConA-stimulated cells at concentrations of 1000 ng/ml. beta Estradiol enhanced the response of NMS cells at concentrations of 500 ng/ml, had no effect on PHA-stimulated cells, and suppressed the response of ConA-stimulated cells at concentrations greater than 500 ng/ml. Testosterone affected only the ConA response, causing suppression at concentrations above 2000 ng/ml. Corticosterone and progesterone caused 80 and 95% suppression, respectively, of the proliferative response to ConA when compared with non-hormone-treated cells. The possible implications of steroid hormone-induced immunosuppression in the pathogenesis of aspergillosis is discussed. PMID- 4026733 TI - Role of litter in the transmission of Campylobacter jejuni. AB - Autoclaved or non-autoclaved used broiler litter that was experimentally contaminated with Campylobacter jejuni was capable of infecting specific-pathogen free chicks maintained in modified Horsfall isolators. Artificially infected chicks became fecal shedders of C. jejuni, resulting in contamination of both autoclaved and non-autoclaved used broiler litter. Fecal shedding of C. jejuni by litter-reared, artificially infected chicks persisted for at least 63 days after chicks were transferred to an isolation unit with a wire floor, which prevented coprophagy. C. jejuni was consistently recovered from water and litter in units housing directly and indirectly infected birds, indicating environmental contamination. These experiments demonstrate the potential role of litter in the perpetuation and transmission of C. jejuni infection in commercial chickens. PMID- 4026734 TI - Isolation of avian paramyxoviruses from sentinel ducks and turkeys in Minnesota. AB - In a 4-year study (1980-1983) involving the use of sentinel ducks that intermingled with wild ducks, a total of 98 paramyxovirus (PMV) isolates (84 Newcastle disease virus, 14 PMV-6) were obtained from 3652 sentinel duck cloacal samples (2.7% isolation rate) collected between June and mid-November each year. PMV infection of sentinel ducks appeared to be seasonal, with the onset of infection occurring between mid-July and mid-August. PMV was not isolated from sentinel turkeys that co-mingled with sentinel ducks during the last 2 years of the study. However, there was serological evidence that the sentinel turkeys were infected with PMV. These findings indicate that wild waterfowl are a natural reservoir of PMV and suggest that interspecies transmission of certain PMV serotypes may occur between waterfowl and turkeys. PMID- 4026735 TI - Mycoplasma gallisepticum vaccination: further studies on egg transmission and egg production. AB - Leghorn hens vaccinated twice with an inactivated Mycoplasma gallisepticum (MG) bacterin before egg production and subsequently challenged with virulent MG were protected against transmission of MG through the egg. Unvaccinated control hens transmitted MG through the egg at a high rate. When unvaccinated hens were vaccinated with MG bacterin 2 weeks after challenge with MG, there was no significant decrease in egg transmission. Hens vaccinated twice before laying did not suffer as severe egg-production drops as unvaccinated hens did when challenged with virulent MG. In a natural MG outbreak in a leghorn breeder flock, 50 hens were separated from the remainder of the flock and vaccinated with MG bacterin approximately 3 weeks after initial exposure. The unvaccinated hens transmitted MG through the egg at a rate three times higher than the rate of transmission of the vaccinated hens. PMID- 4026736 TI - Vitamin A toxicity: comparative changes in bone of the broiler and leghorn chicks. AB - Severe skeletal lesions were produced in both broilers and leghorns orally administered toxic levels of vitamin A (330 or 660 IU vit. A/g body weight X day) for 21 consecutive days. Hypervitaminosis A in broilers produced an osteodystrophy characterized by abnormal thickening of the proliferative maturation zone, metaphyseal sclerosis, hyperosteoidosis, decreased number of osteoclasts, and parathyroid gland hyperplasia. In leghorns, the osteodystrophic lesions were characterized by a thin proliferative-maturation zone, a relatively thickened hypertrophy zone, flattened spindle-shaped osteoblasts, and osteoporosis. In both broilers and leghorns given excessive vitamin A, the osteogenic layer of periosteum in all bones was thin. PMID- 4026737 TI - Antibiotic aerosolization: tissue and plasma oxytetracycline concentrations in turkey poults. AB - Oxytetracycline hydrochloride (OTC) was delivered by aerosol to healthy 3-week old turkeys. Trachea, lung, and plasma were evaluated for OTC levels at 1, 4, 8, 12, 24, and 48 hours after aerosol exposure. In Expt. 1, 15 poults in a modified Horsfall unit were exposed to 1 g OTC/m3 of air using a DeVilbiss ultrasonic nebulizer. In Expt. 2, 25,000 poults in a commercial confinement unit were exposed to 0.075 g of OTC/m3 of air using a Fogmaster fogger. In each case, initially high tracheal and lung OTC concentrations were obtained. OTC levels in the trachea fell to less than 1 microgram/g between 4 and 8 hours postexposure. Plasma OTC levels remained low throughout both experiments. Oxytetracycline was still detectable in room air 60 min after aerosol exposure and before ventilation was restored. This method of administration may have promise for use in respiratory infections, but additional studies are needed to further define the use of aerosol therapy in poultry production units. PMID- 4026738 TI - Isolation and identification of Aegyptianella pullorum (Rickettsiales, Anaplasmataceae) in wild turkeys from North America. AB - Isodiagnosis of blood from Rio Grande wild turkeys from southern Texas revealed a small, intraerythrocytic rickettsia, Aegyptianella pullorum Carpano, 1928, in 24 of 300 samples. Identification of this first isolate from North America was made using both light and transmission electron microscopy. It is suggested that the translocation of wild turkeys from Texas to other states could spread this pathogen to both wild birds and domestic poultry. PMID- 4026739 TI - Laboratory evaluation of Newcastle disease vaccination programs for broiler chickens. AB - Experiments were conducted to examine the efficacy of various commercial vaccination programs for the prevention of Newcastle disease (ND) in broilers. In all, chicks were from breeders vaccinated against ND via drinking water at 75-day intervals. Vaccination was by company personnel on company premises. In Expt. 1, the initial ND vaccination programs tested were vaccination at 1 day by coarse spray with the Spra-Vac machine or by tracheal instillation with the Beak-o-Vac machine, and vaccination at 7 days via drinking water. In Expts. 2-4, birds initially vaccinated via one of the three previously mentioned methods (Spra-Vac in Expt. 2, Beak-o-Vac in Expt. 3, and drinking water in Expt. 4) were revaccinated against ND by either drinking water or coarse spray with one of two commercial portable machines (ULVA Fan or Spray Master). Serologic and challenge data in Expt. 1 indicated that although broilers vaccinated by any of the three initial routes failed to produce measurable antibody to NDV, all methods resulted in protection against NDV challenge at 35 and 49 days. However, resistance to challenge with virulent ND was greatest in birds initially vaccinated by coarse spray with the Spra-Vac machine. Results in Expts. 2-4 indicated that NDV hemagglutination-inhibition titers were highest and resistance to challenge greatest in birds initially vaccinated at day 1 by coarse spray (Spra-Vac) and then revaccinated at 14 days by coarse spray. There were no differences, however, between the portable coarse spray machines in efficacy in reimmunizing broilers against NDV. PMID- 4026740 TI - Encephalomalacia associated with hypovitaminosis E in turkey poults. AB - Four-to-five-week-old turkey poults fed a diet markedly deficient in vitamin E (alpha-tocopherol) abruptly developed neurologic signs such as tremor, incoordination, and recumbency shortly after being moved to new quarters. Serum concentrations of alpha-tocopherol in birds on this diet were significantly lower than control values. Associated lesions included recent ischemic necrosis of the cerebellum and spinal cord. The condition closely resembled nutritional encephalomalacia of chicks. This report represents the initial published description of that entity in turkeys. PMID- 4026741 TI - Exencephaly in araucana chickens and silkie bantams. AB - Exencephaly and hydranencephaly were diagnosed in two 6-week-old araucana chickens (Gallus domesticus) and one adult silkie bantam (Gallus domesticus). The chickens were presented with large, subcutaneous, cranial soft-tissue masses and exhibited neurological signs. There was partial aplasia of the frontal bones, resulting in herniation of the cerebral hemispheres. PMID- 4026742 TI - Cryptosporidiosis in the respiratory tract of turkeys in Saskatchewan. AB - Developmental stages of Cryptosporidium sp. (Protozoa: Cryptosporiidae) were observed in tracheal epithelium of two groups of turkey poults from a farm in central Saskatchewan. Lesions associated with the parasite included excess mucus, epithelial hyperplasia and metaplasia and necrosis, and macrophage and heterophil infiltration in thickened lamina propria. Infection with the parasite was confirmed by histologic and ultrastructural examination of tracheal tissues. PMID- 4026743 TI - A rapid method for renal vascular perfusion for light and transmission electron microscopy of chicken kidney. AB - A rapid and easily performed vascular-perfusion technique for avian kidney is described. This procedure uses 30 cm3 of fixative per adult bird, requires less than 1 minute, and results in fixation of one caudal renal division suitable for light or transmission electron microscopy. Kidneys fixed by this method were superior to those fixed by rapid immersion when compared by light and transmission electron microscopy. PMID- 4026744 TI - The stress of work: an overview. AB - This paper looks at a number of potential occupational stressors found to predict job dissatisfaction and ill health (both mental and physical) in a variety of different occupational settings. Factors intrinsic to the nature of the job, role ambiguity and conflict, poor relationships at work, lack of career development, inadequate organisation structure/climate, and problems associated with the interface between work and homelife are the focal points of attention. Many of these sources of occupational stress are prevalent in the field of aviation, and may be exacerbated by the move toward deregulation and increasing commercial competition within the industry. PMID- 4026745 TI - Occupational stress and the professional pilot: the role of the Pilot Advisory Group (PAG). AB - This paper discusses the role of pilot peer group involvement, using the Pilot Advisory Group (PAG), in assisting pilots who manifest personal problems which derive from occupational and other stressors. Some general aspects of "background" occupational stress are discussed. Attitudes and opinions of professional aviators are identified and their role in denial of symptomatology is developed. The concept of the Pilot Advisory Group (PAG) is then discussed in detail before its role in relation to occupational stress is introduced. While some of the better known problems associated with occupational stress in pilots are mentioned, the emphasis in the paper is on developing new perspectives regarding the identification of stress-induced dysfunction, and also in exploring the suitability of PAG involvement. The formal obligations of management and regulatory authorities are contrasted with what the author sees as the countervailing imperatives of pilot attitudes and beliefs. PMID- 4026746 TI - The endocrinology of stress. AB - With the advance in hormone assay techniques it has been demonstrated that stress may be characterised by a number of endocrinological changes which are not limited solely to the secretion of catecholamines and adrenal steroids. This article reviews the effects of various stressors on these and other hormones. Aviation is a source of a wide range of stressors including radial acceleration (+Gz) Since its magnitude and duration may be controlled experimentally by using the human centrifuge, it is possible to quantify such a stressor when investigating endocrinological markers of stress. Sustained +Gz acceleration results in a "dose-dependent" secretion of cortisol, i.e. the higher the acceleration, the greater the cortisol secretion. In addition, increases in the concentrations of arginine vasopressin and catecholamines occur but these are not accompanied by changes in prolactin or growth hormone. PMID- 4026747 TI - Stress, catecholamines, and sleep. AB - Difficulties in defining stress stem from its subjective nature. Measurements of stress based on its effects on physical and mental morbidity tend to be speculative because of the multifactorial causation of stress-related diseases, and the characteristically long time-lag between stress states and morbidity. In this study catecholamine output was measured in a group of adults Oxfordshire villagers and the observed variations were related to their lifestyles and health perceptions. A marked circadian variation was observed with adrenaline showing the most marked associations with lifestyle. In men it was possible to account for a relatively high proportion of the variation in adrenaline excretion by relating values to certain factors associated with stress. In women there appears to be a similar association between adrenaline output and the social class of the husband. Data were also obtained on sleep characteristics, which were assessed with regard to lifestyle. Very broadly, sleep duration is related to the level of waking activity, while sleep latency and quality are correlated with people's self-perception of health. PMID- 4026748 TI - Factors predictive of stress, organizational effectiveness, and coronary heart disease potential. AB - Research to predict stress, organizational effectiveness, and potential for developing coronary heart disease (CHD) is presented based on two samples (n = 357 and n = 225). Results indicate that perceived stress is predicted by a combination of individual and job related characteristics. The data suggest that stress, in turn, affects individual and organizational health and effectiveness, by causing increases in cold/flu episodes, somatic symptoms, while decreasing job satisfaction. In addition, stress has an indirect effect on job performance and absenteeism. Models for predicting the ratio of total serum cholesterol divided by HDL cholesterol as an indicator of coronary heart disease potential are provided and a CHD screening model is proposed. PMID- 4026749 TI - Changes of posture during transient perturbations in microgravity. AB - The control of goal-directed arm movement and of body stability before, during, and 3 d after a 7-d spaceflight has been investigated. The findings show that the anticipatory and compensatory activities of the postural muscles were highly reproducible during the first days of the space mission. The sequence of these activities, studied in two situations--in which the platform either was fixed or could rotate about near the rotation axis of the ankle--was similar to a ground based situation. The trajectory of various body segments demonstrates that a 7-d exposure to microgravity did not result in major changes in posture. Furthermore, vision seemed to play an important role in the control of standing posture at the beginning of the flight. Postural perturbations, elicited by unexpected displacements of the foot support, involved leg muscle reflexes whose amplitudes were greatly reduced compared to those on earth. PMID- 4026750 TI - Puma (SA 330) helicopter impact simulation: demonstration of the efficiency of the French crashworthy seat. AB - An experiment examining the accelerations encountered during a helicopter crash has been conducted on the SA 330 Puma. The measures recorded from anthropomorphic dummies used in this experiment clearly demonstrated the efficiency of crashworthy seats. Very high levels of acceleration recorded on the aircraft floor are attenuated by the seat. Neither phase shift nor amplification have been observed in the elastic response of the various parts of the dummies' bodies (head-chest-pelvis). The four point restraint harness was also found to be very efficient. However, the extrapolation of results obtained from dummies can be misleading. Original data processing technics and interpretation methods have been developed for this experiment. They might allow the prediction of human tolerance to crash accelerations with a fair safety margin. PMID- 4026751 TI - Differences in health risks by aircraft model among U.S. Navy pilots. AB - The purpose of this study was to identify health risks associated with eight aircraft models in a population of U.S. Navy pilots (n = 22,245) during a 12.5 year time period. Results showed that pilots in the trainer/miscellaneous group (less than or equal to 35 years of age) had significantly higher hospitalization rates than other pilot groups for almost all diagnoses whereas reconnaissance pilots were distinguished from others by lower total hospitalization rates. Younger helicopter pilots had significantly higher hospitalization rates for joint diseases than four other groups and significantly higher rates for nervous system disorders than attack and patrol/antisubmarine groups. Explanations for these and mortality rate results were provided by examining the influence of selection and retention criteria; age, experience, and exposure; pilot population characteristics; and aircraft model assignments. PMID- 4026752 TI - Effects of exercise-heat acclimation on fluid, electrolyte, and endocrine responses during tilt and +Gz acceleration in women and men. AB - Plasma fluid, electrolyte, protein, renin, and vasoactive hormone (epinephrine, norepinephrine, vasopressin) responses were measured in six women (21-23 yr) and four men (21-38 yr) before and immediately following an orthostatic tolerance test (70 degrees head-up tilt) and a +Gz (head-to-foot) acceleration tolerance test (0.5 G X min-1 linear ramp to grayout). These tests were conducted before and after 12 consecutive days of exercise-heat acclimation when the subjects exercised on a cycle ergometer at a relative oxygen uptake of 44% to 49% peak oxygen uptake in a hot environment (Ta = 40 degrees C, 42% rh). During acclimation plasma volume increased by 10.6% (p less than 0.05) in the women and by 11.9% (p less than 0.05) in the men; in both groups exercise heart rate decreased significantly. After acclimation, acceleration tolerance was unchanged in both groups (range 3.1 to 3.4 G); the women's tilt tolerance was unchanged (range 33.6 to 39.5 min), but the men's tilt tolerance increased from 30.4 min before to 58.3 min (delta = 91%, p less than 0.05) after acclimation. Since the pattern of fluid, electrolyte, and protein shifts and acceleration tolerances in the women and men were virtually the same, the hormone responses were highly variable, and the men's tilt tolerance increased significantly after acclimation, it is clear that responses to tilting cannot be used to predict responses to acceleration. Analysis of data from the present study and the literature suggests that current exercise training regimes should be unrestricted for astronauts who have not previously been highly endurance trained.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4026753 TI - Effects of deceleration on the humoral antibody response in rats. AB - The purpose of this experiment was to determine the effects of hyper-gravity (hyper-G) followed by a return to normal gravity (deceleration) on the immune system of rats. Hyper-G was simulated by chronic centrifugation. Eighteen 35-d old male rats were divided into three groups of six rats each. Two groups were exposed to 2.1 G and 3.1 G, respectively, for 28 d. The third group served as 1.0 G controls. Rats were removed from the centrifuge on day 29. All rats were immunized with sheep red blood cells (SRBC) on days 29, 42, and 57; rats were bled on days 36, 47, and 62. Hematocrits and anti-SRBC titers were determined each day the rats were bled. White blood cell (WBC) counts were determined on day 47. On day 63, all rats were sacrificed and organ:body mass ratios obtained for a number of organs. Centrifuged rats ate and gained significantly less. The organ:body mass ratios for the adrenal glands, kidneys, lungs, heart, and thymus were unaffected by deceleration. Although marginally significant (p less than 0.05) decreased organ:body mass ratios were found for the liver and spleen in the 3.1 G group, this effect may not be real, due to the small number of rats used. No significant differences were found in hematocrits, WBC counts, or anti-SRBC titers. These experiments indicate that deceleration does not adversely affect these particular aspects of the immune system. However, they do not preclude the possibility that other aspects of the immune system, such as interferon or complement, may be affected. PMID- 4026754 TI - HDL-cholesterol related to weight, smoking, and physical fitness in German Air Force pilots. AB - This study was undertaken to find out the importance of HDL-cholesterol in assessing coronary risk in our pilots. We related cholesterol, HDL-cholesterol, and the cholesterol/HDL-cholesterol ratio in blood to the BROCA-Index, smoking, and relative PWC 150 in 589 individuals. We found positive correlations between the cholesterol/HDL-cholesterol ratio to the BROCA-Index and to smoking. We did not find any correlation between cholesterol alone and the BROCA-Index or smoking. Moreover, we failed to find any correlations to physical fitness calculated from PWC 150. That may be due to the higher physical fitness standard in our pilots in comparison with the normal population. It is concluded, that a HDL-cholesterol determination is a more relevant parameter than cholesterol alone in borderline and elevated cholesterol levels. PMID- 4026755 TI - Age and space flight. AB - Criteria for space flight crew and passenger selection should be based on the following three considerations: (1) freedom from impairing disease, (2) ability to perform mission requirements and (3) motivation to undertake the mission. Chronologic age of itself is not a valid criterion. Forecast life expectancy and vitality relative to mission duration are valid criteria and can be applied on an individual basis using modern assessment techniques. The good health and vitality characterizing the upper ages of today's population widens the opportunity to utilize increasingly broad fields of experience and skills in future space flights, further enhancing the odds for total mission accomplishment. PMID- 4026756 TI - Lt Paul R. Wolff, MC, USNR, saves crewmen during ordeal within collapsed aircraft fuselage after crash. AB - Lt Paul R. Wolff, MC, USNR, is the first to receive Pride and Professionalism recognition for his heroic and professional action while responding to the crash of a Japanese Maritime Self Defense Force PS-1 aircraft. At the time of the crash, Dr. Wolff was assigned as the senior flight surgeon representing the First Marine Aircraft Wing and Naval Regional Medical Center Branch Clinic, Marine Corps Air Station, Iwakuni, Japan. On 26 April, 1983, the aircraft crashed just outside the perimeter of the Marine Corps Air Station. Lt Wolff was the first medical person to arrive at the crash site and immediately took charge of the medical aspects of the rescue. Upon learning that several air-crew members were still trapped inside the smoldering wreckage, he unhesitatingly and with complete disregard for his personal safety while fully aware of the personal dangers involved, entered the wreckage to provide medical care to the injured during a 4 hour period. Lt Wolff's bravery, superlative knowledge, exceptional skills, and outstanding leadership abilities under extremely dangerous circumstances led to saving the lives of three crewmen who were trapped. Below is a narration of the events that took place after the crash and Lt Wolff's medical response in the ensuing hours. It is given by Lt Wolff as he recounts the events. PMID- 4026757 TI - Space exploration and innovative developments in the aerospace industry. PMID- 4026758 TI - DDT--susceptibility status of Anopheles philippinensis--a mosquito vector of malaria in Bangladesh. AB - DDT-susceptibility tests conducted on An. philippinensis Ludlow in 1979 and 1980 and several previous years of observations made during malaria programmes in different areas of Bangladesh have been reported. The LC50 value for 1980 was found to be 0.74% DDT showing 2.96 and 1.85 fold increase of tolerance level from 1961 (0.25%) and 1976 (0.4%) respectively. The tests showed that the species continues to be susceptible to DDT in Bangladesh. However, the changes in LC50 over the years may indicate a slight acquisition of "vigour tolerance." PMID- 4026759 TI - Correlation of percutaneous transhepatic cholangiogram with operative findings. AB - Percutaneous transhepatic cholangiography (PTC) diagnosis of extrahepatic biliary obstruction was correlated with laparotomy findings. Out of a total of 55 cases who had PTC, 28 underwent laparotomy. PTC diagnosis of the cause of obstruction was correct in 93 percent of them. The differentiation of benign from malignant lesion was accurate in all the cases. It is concluded that PTC is valuable in the diagnosis of the cause of extrahepatic obstruction. PMID- 4026760 TI - Clinical profile of rheumatic fever in some hospitalised children of Bangladesh. AB - Clinical profile of rheumatic fever (RF) in 100 hospitalised children of Bangladesh were studied. Peak age period of the incidence of the disease was found in the age group of 11-12 years (34 percent) and majority (83.5 percent) of the cases belonged to the middle and poor classes. There was slight preponderance of the male. Carditis was the commonest (64 percent) manifestation followed by poly-arthritis (51 percent). Chorea was present in 6 percent and subcutaneous nodules were in 7 percent cases. Erythema marginatum (EM) was conspicuous by its absence. Amongst the rheumatic heart diseases (RHD), mitral stenosis (MS) and mitral incompetence (MI) comprised the highest (35 percent) incidence and next to it was the MS (13 percent) and MI (9 percent). PMID- 4026761 TI - Study of awareness during noninhalational anaesthesia. AB - Forty-five adult patients underwent a noninhalational anaesthetic method for investigation of awareness during surgery and recall of events associated with surgery in postoperative period. All the patients were divided into two groups. The first group of patients were male and had upper abdominal operations. The second group were female and had lower abdominal operations. No significant difference was found between these two groups either in requirements of depth of anaesthesia or in the evidence of per-operative awakefulness. Eighty percent patients of both the groups showed various signs of peroperative awakefulness but did not recall any events associated with surgery in the postoperative period. There was no report of dream either. PMID- 4026763 TI - Structured exploratory data analysis: a critique. PMID- 4026762 TI - A study of familial resemblance for two cognitive psychometric tests by permutation analyses. PMID- 4026764 TI - Morphometric studies in inbred and hybrid house mice. VI. A genetical analysis of brain and body size. PMID- 4026766 TI - Responses of male mice to odors of females: effects of T- and H-2-locus genotype. PMID- 4026767 TI - Depressive symptoms and unprompted causal attributions: content analysis. PMID- 4026765 TI - The genetic architecture of hyponeophagia and the action of diazepam in rats. PMID- 4026768 TI - The nature of depressive and anxious, intrusive thoughts: distinct or uniform phenomena? PMID- 4026769 TI - A behavioral-analytic model for assessing social skills in blind adolescents. PMID- 4026770 TI - Expectancy bias in behavioral observations of therapeutic outcome: an experimental analysis of treatment and halo effects. PMID- 4026771 TI - Predictors of depressive mood in mothers of clinic-referred children. PMID- 4026772 TI - The etiology and maintenance of severe animal phobias. PMID- 4026773 TI - A methodological and empirical critique of psychotherapy outcome meta-analysis. PMID- 4026774 TI - Fears in children and adolescents: normative data. PMID- 4026775 TI - Male and female agoraphobia: are they different? PMID- 4026776 TI - Effects of a recreation therapy program on activity involvement and social interaction of mentally-retarded persons. PMID- 4026777 TI - Is worry a valuable concept? PMID- 4026778 TI - Worry: a potentially valuable concept. PMID- 4026779 TI - Histochemical localization of acetylcholinesterase in blood cells. AB - Cholinesterase activity was detected by histochemical methods in normal human blood smears. In erythrocytes, acetylcholinesterase was found to be localized in the cortical region of the cells and, to a lesser degree, in the inner cytoplasm. In leucocytes, cholinesterase activity was found around the nuclear membrane and in the cytoplasm. The specificity of the enzymic activity was ascertained by using selective inhibitors. PMID- 4026781 TI - Binding of concanavalin A to secretory epidermis in the fish Blennius sanguinolentus pallas: light microscopic and ultrastructural studies. AB - Concanavalin A (Con A) lectin from jack bean Canavalia ensiformis DC binds to alpha-D-glucopyranosyl and alpha-D-mannopyranosyl residues of the cuticular secretions (glycocalyx) attached to apical plasma membrane in the skin surface cells of Blennius sanguinolentus. The presence of Con A positive carbohydrate components is also observed in some secretory vesicles close under the apical cell membrane and in the goblet cell secretion spread over the surface of the skin. Other lectin labeling methods might offer a new tool for the cytochemical demonstration of glycoconjugates containing sugar residues on plasmic membranes of the epithelial cells. This can provide an insight into the functional significance of the carbohydrate moieties, attributable to the specialization of the cell membranes. PMID- 4026780 TI - Internalization of cycloheptaamylose-dansyl chloride complex during labelling of surface membrane in living Paramecium aurelia cells. AB - Internalization of cycloheptaamylose-dansyl chloride complex during surface labelling of living long-term starved Paramecium aurelia cells has been observed. This process may be inhibited by pretreatment of the ciliates with dichloroisoproterenol. Uptake of cycloheptaamylose-dansyl chloride may be visualized only after UV preirradiation: the appearance of orange-fluorescing vacuoles of diameter 2.3-4.5 micron may then be observed. Microspectrographic analysis performed on the cells and dansyl derivatives indicates that this fluorescence is produced by a photochemical reaction of dansyl chloride - released from CDC complex inside the digestive vacuoles-under the influence of UV irradiation. PMID- 4026782 TI - Effect of vasopressin on phasic coronary blood flow. AB - The effects of vasopressin on the coronary circulation have been studied with regard to its general hemodynamic effects. Aortic blood pressure (BP), left ventricular pressure (LVP), aortic blood flow (AoBF), and circumflex blood flow (CBF), were measured in 12 open-chest dogs, under control conditions and during vasopressin infusion (25 mU/kg/min). During vasopressin infusion, the mean aortic blood pressure (MBP) was increased from 104 +/- 23 mm Hg to 161 +/- 23 mm diastolic blood pressure (DBP) was more increased (+55%) than the systolic blood pressure (SBP) (+40%). AoBF was decreased from 2.169 +/- 0.408 l/min to 1.118 +/- 0.303 l/min; and the heart rate was decreased by 18%. The total combined left ventricular power did not change significantly. The increase in total peripheral resistance (TPR) (+200%) was the main change in impedance spectrum. The mean circumflex coronary blood flow (MCBF) was decreased from 48 +/- 8.6 ml/min to 33.4 +/- 9.7 ml/min. This decrease was more important in the diastolic circumflex blood flow (DCBF) (-33%) than in the systolic one (-0.8%). The diastolic pressure time index (DPTI) was more increased than the systolic pressure time index (SPTI). The DPTI/SPTI ratio was increased from 0.91 to 1.3. Long diastoles, induced by vagus nerve stimulation, have permitted to characterise the relationship between pressure and coronary blood flow during diastole. This relationship was linear under basal condition, and during vasopressin perfusion. This made it possible to determine the critical closing pressure (Pf0), and the coronary conductance (the slope of the regression curve). Vasopressin induced an increase in Pf0, from 33.7 +/- 95 to 77.4 +/- 16.07 mm Hg (p less than 0.001), and a decrease in coronary conductance, from 0.8 +/- 0.32 to 0.5 +/- 0.1 ml/min/mm Hg. The effect of an acute change in perfusion pressure on the coronary flow, under control conditions and during vasopressin infusion was studied by opening a large arteriovenous fistula. Unclamping of the fistula, under control conditions, allowed to realize an acute fall in DBP from 82.5 +/- 6.36 to 35.5 +/ 9.19 mm Hg, and in DCBF, from 58.5 +/- 9.2 to 20 +/- 9.8 ml/min. During vasopressin infusion, a similar fall in perfusion pressure lead to a zero diastolic circumflex blood flow, for a diastolic aortic blood pressure of 56 +/- 12 mm Hg. However, vasopressin did not affect the delayed active coronary vasodilatation. PMID- 4026783 TI - Uncoupler- and hypoxia-induced damage in the working rat heart and its treatment. II. Hypoxic reduction of aortic flow and its reversal. AB - In the working rat heart we investigated heart function (aortic and coronary flow) during a normoxic, a hypoxic, and a reoxygenation phase after hypoxia. A depressed heart function was obtained by limiting oxygen supply and reducing left ventricular filling pressure (preload). After hypoxic perfusion for about 90 min, reoxygenation resulted in a 50% decrease of aortic flow. Lactate production and release increased immediately after oxygen deprivation and reached a maximum after about 35 min of hypoxia. Following reoxygenation, lactate release decreased. Lactate dehydrogenase became significant after reoxygenation. After stabilization of aortic flow at 50% in the reoxygenation phase different reagents were examined for their influence on heart performance. 1.5 mM of 2 Mercaptopropionylglycine (MPG) significantly increased aortic flow by 40%. The oxidized form of MPG (ox-MPG) at a concentration of 0.6 mM increased aortic flow by 125%. A molecular mechanism is proposed involving reorientation of the ATPase molecules at their membrane sites. PMID- 4026784 TI - Depletion of membrane phospholipid and mitochondrial dysfunction associated with coronary reperfusion. AB - The role of phospholipase (PLase) in the development of heart mitochondrial dysfunction following reperfusion was studied together with the effects of dilazep on the action of PLases and reperfusion injury. In vivo experiment: Seventy six adult mongrel dogs were divided into 3 groups; the control group (n = 36), the dilazep 0.5 mg group (n = 17) and the dilazep 1 mg group (n = 23). Fifteen min after premedication with physiological saline or dilazep (0.5 mg/kg or 1 mg/kg), the left anterior descending coronary artery was occluded for 15 min and then reperfused for 5 min. Each group was further divided into two subgroups depending on the presence or absence of reperfusion arrhythmia. Immediately after 5 min of reperfusion, myocardial mitochondria were prepared from the normal and the reperfused areas. Pretreatment with dilazep induced a dose-dependent decrease in the incidence of reperfusion arrhythmia from 31% of the control to 24% (0.5 mg/kg) and 9% (1 mg/kg). In the arrhythmia cases in each group, functional deterioration of mitochondria from the reperfused area was observed with the increase in free fatty acids and the decrease in phospholipids in the reperfused mitochondria. In vitro experiment: Using L-alpha-dimyristoyl phosphatidylcholine as a substrate, myristic acid released by PLase A2 or by PLase C with or without pretreatment by dilazep was quantitatively determined. Dilazep inhibited the release of myristic acid by PLase A2 or by PLase C in a concentration-dependent manner. These results suggest that decomposition of mitochondrial membrane phospholipids caused by PLase activation following reperfusion was primarily responsible for the development of mitochondrial dysfunction, and that dilazep showed beneficial effects against reperfusion injury by inhibiting the action of PLases. PMID- 4026785 TI - Platelet depletion in experimental myocardial infarction. AB - Accumulation of platelets in the microvasculature after acute myocardial ischemia may exacerbate tissue injury through the formation of microthrombi and by the release of vasoactive substances. To assess the role of platelets in myocardial ischemic injury and infarction, circulating platelets were reduced by 94 +/- 2% (mean +/- S.E.M.) with sheep antiserum to canine platelets. Regional myocardial ischemia was produced by occlusion of the left circumflex coronary artery (LCCA) for 90 min followed by reperfusion for 5 hours. Infarct size did not differ significantly between antiplatelet serum and nonimmune serum groups: 36 +/- 8 vs. 43 +/- 4% of the area at risk, determined by a post-mortem dual staining technique (p greater than 0.05). A second occlusion-reperfusion control group, sacrificed at 24 hours, did not differ from 5 hr reperfused groups with regard to infarct size. Coronary sinus thromboxane B2 (TXB2) concentrations were not altered significantly by platelet depletion. Histopathologic examination confirmed the presence of necrosis in the infarcted myocardium and revealed substantial leukocytic infiltration in both groups. The results suggest that circulating platelets are not required for the full expression of myocardial ischemic injury resulting from temporary coronary artery occlusion followed by reperfusion. PMID- 4026786 TI - Functional and reactive hyperemia are unaltered by homocysteine in conscious dogs. AB - The purpose of this study was to test the hypothesis that L-homocysteine thiolactone (L-HCTL), through its reaction with adenosine to form S adenosylhomocysteine, may modulate myocardial functional and reactive hyperemic responses. Reactive hyperemic responses to 10-sec occlusions or 400-msec diastolic occlusions of the circumflex coronary artery and functional hyperemic responses to ventricular extra-activations were studied in a chronic heart blocked dog preparation during a control period and following L-HCTL (40 mg/kg). In two additional dogs multiple venous blood samples and left ventricular myocardial biopsies were obtained following L-HCTL to measure changes in plasma homocysteine and tissue S-adenosylhomocysteine. Despite a 75-fold increase in peak plasma homocysteine and a 26-fold increase in tissue S-adenosylhomocysteine, L-HCTL did not alter myocardial functional and reactive hyperemic responses. The rapid increase in myocardial S-adenosylhomocysteine confirmed cellular entry of homocysteine and its reaction with endogenous adenosine. The failure of L-HCTL to alter functional and reactive hyperemic responses suggests that either such treatment does not affect myocardial release of adenosine or that adenosine is not an important regulator of coronary flow. PMID- 4026787 TI - Fentanyl, Na-pentobarbital and halothane influence myocardial infarct size. AB - We investigated the effects of three anesthetics on the size of myocardial infarction and on blood flow distribution within the myocardial wall. Myocardial infarcts were induced in 34 dogs by ligating a coronary artery for 90 minutes, and permitting reflow for 90 minutes. The anesthetics used were fentanyl, Na pentobarbital, and halothane. Under halothane the mean blood pressure (BP) during coronary artery ligation was 113 +/- 2/82 +/- 2 mm Hg and the heart rate (HR) was 135 +/- 2/min. Under fentanyl, the BP was 143 +/- 3/91 +/- 2 mm Hg and HR 99 +/- 3/min. Under Na-pentobarbital, BP was 141 +/- 2/104 +/- 2 mm Hg and HR 146 +/- 2/min. A higher mean BP combined with a slower HR, as seen under fentanyl, was associated with the smallest infarct (24 +/- 8%). Low BP and higher HR, as seen under halothane, was associated with the largest infarct (51 +/- 5%). Na pentobarbital, with a higher BP but also a faster HR, resulted in an infarct size of 32 +/- 5%. We conclude that a higher mean BP combined with a slower HR might favor the preservation of a larger mass of vulnerable myocardial tissue in a totally occluded coronary artery. PMID- 4026790 TI - [Total fasciectomy in the treatment of Dupuytren contracture]. PMID- 4026789 TI - [Functional anatomy of the finger extensor mechanism under physiological and pathological conditions. I]. PMID- 4026788 TI - Effects of angiotensin and ergonovine on large and small coronary arteries in the intact dog. AB - Angiotensin (ATN) and ergonovine (ERG) are known to cause vasoconstriction of the coronary bed. However, ATN effects have been described mainly on the coronary resistance vessels, while ERG effects have been described on proximal conductance vessels. Recent studies have shown that proximal and distal coronary arteries are regulated independently. To examine both proximal and distal effects of ATN and ERG on the same heart, we studied 7 intact dogs, anesthetized with Innovar (Fentanyl 0.4 mg, Droperidol 20 mg, in 1 ml) and nitrous oxide, which were subjected to direct left anterior (LAD) coronary infusion of angiotensin (0.1, 0.5 and 5 micrograms/min) and ergonovine (0.5, 5, and 25 micrograms/min). Using a quantitative angiographic technique to measure artery dimensions and microspheres to measure flow, ERG infusion showed significant large artery constriction at all doses (maximum: 38.9 +/- 7.8% area reduction), and a significant decrease in LAD coronary artery flow, while endocardial/epicardial flow ratio remained unchanged. ATN produced a biphasic effect on the large coronary arteries. The lowest dose produced constriction (12.3 +/- 3.7% area reduction), which returned toward control value with the 0.5 micrograms/min dose (6.0 +/- 1.0% area reduction), and the 5 micrograms/min dose (1.5 +/- 9.5% area reduction), and no significant changes were observed in LAD flow with ATN infusion. Endocardial/epicardial ratio was unchanged, but aortic pressure was significantly increased during 0.5 and 5 micrograms/min ATN infusion. Coronary resistance (pressure/flow) increased with both ERG and ATN. ERG and ATN produce large and small coronary artery constriction. The coronary response to ERG in dogs is similar to the human coronary response, even though previous data indicated a minimal constrictor response to ERG in canine coronary arteries. PMID- 4026791 TI - [Problems in the diagnosis of dystrophic bone diseases]. PMID- 4026792 TI - [Spinal traction syndrome (cast syndrome)--etiology, diagnosis, therapy and prevention]. PMID- 4026793 TI - [Current diagnosis of diastematomyelia]. PMID- 4026794 TI - [Equine leukosis. 2. Clinical aspects and pathology in our own patients]. PMID- 4026795 TI - Characterization of [3H]di-isopropyl phosphorofluoridate-binding proteins in hen brain. Rates of phosphorylation and sensitivity to neurotoxic and non-neurotoxic organophosphorus compounds. AB - The experiments described in this paper were designed to isolate [3H]di-isopropyl phosphorofluoridate-binding proteins by sodium dodecyl sulphate/polyacrylamide gel electrophoresis for the purpose of characterizing and identifying potential initiation sites for organophosphorus-compound-induced delayed neurotoxicity. The major Paraoxon-insensitive Mipafox-sensitive binding protein (Mr 160 000) was found to be identical with one previously identified as neurotoxic esterase, an enzyme that has been proposed to be the target site for organophosphorus-compound induced delayed neurotoxicity. However, two other binding proteins with suitable binding characteristics were also found in smaller amounts, one of which has not been detected previously. Di-isopropyl phosphorofluoridate was found to phosphorylate all three of these proteins at rates similar to the rate at which neurotoxic esterase is inhibited by di-isopropyl phosphorofluoridate. Varying the concentration of di-isopropyl phosphorofluoridate or the time of incubation produced similar increases in binding to each of the labelled proteins. This suggests that the reaction rates of di-isopropyl phosphorofluoridate with proteins may be described by first-order kinetics, and the concentration of the Michael is complex formed during binding is minimal for all the phosphorylated proteins. The recovery of the binding activity in the 160 000-Mr band was found to be similar to the recovery of neurotoxic esterase activity, lending further support to the contention that this band is identical with neurotoxic esterase. PMID- 4026796 TI - Cysteamine depletes cystinotic leucocyte granular fractions of cystine by the mechanism of disulphide interchange. AB - Cystinotic lysosome-rich leucocyte granular fractions, loaded with [35S]cystine, were exposed to different cystine-depleting agents. During a 30 min incubation at 37 degrees C, untreated cystinotic granular fractions lost negligible [35S]cystine when corrected for lysosome rupture. Granular fractions exposed to 0.1 mM-cysteamine lost 64% of their initial cystine, and hexosaminidase activity was decreased by 10%. This was accompanied by the formation of high concentrations of [35S]cysteine-cysteamine mixed disulphide within the granular fraction pellet, and, in the presence of N-ethylmaleimide, increasing amounts of [35S]cysteine-N-ethylmaleimide adduct outside the granular fraction. In separate experiments, [35S]cystine exited cystinotic leucocyte lysosomes at a negligible rate (half-times 199 and 293 min), but [35S]cysteine-cysteamine mixed disulphide exhibited substantial egress (half-times 66 and 88 min) and was recovered intact outside the granular-fraction pellet. We conclude that cysteamine depletes lysosomes of cystine by participating in a thiol-disulphide interchange reaction to produce cysteine and cysteine-cysteamine mixed disulphide, both of which traverse the cystinotic leucocyte lysosomal membrane. PMID- 4026797 TI - Collagen fibril formation in the presence of sodium dodecyl sulphate. AB - Sodium dodecyl sulphate (SDS) was used to weaken both the electrostatic and the hydrophobic interactions during collagen fibrillogenesis in vitro. The rate and extent of fibril formation as well as fibril morphology were affected by SDS concentration. Both the formation of large fibrils at 0.3 mM-SDS and the complete cessation of fibril formation at 0.5 mM-SDS were considered to be the result of SDS-induced conformational changes in the non-helical telopeptides. A possible mechanism of SDS interaction with the N-terminal and the distal region of the C terminal telopeptides is offered. PMID- 4026798 TI - Hormone-induced increase in free cytosolic calcium and glycogen phosphorylase activation in rat hepatocytes incubated in normal and low-calcium media. AB - The action of alpha 1-adrenergic agonists (noradrenaline in the presence of propranolol), vasopressin and angiotensin on the intracellular free Ca2+ concentration, [Ca2+]i, was determined by using the fluorescent dye quin2 in isolated rat liver cells. In the presence of external Ca2+ (1.8 mM), 1 microM noradrenaline induced an increase in [Ca2+]i up to about 800 nM without apparent delay, whereas 10 nM-vasopressin and 1 nM-angiotensin increased [Ca2+]i to values higher than 1500 nM with a lag period of about 6s. The successive addition of the hormones and of their specific antagonists indicated that the actions of the three Ca2+-mobilizing hormones occurred without apparent desensitization (over 6 min) and via independent receptors. The relative contributions of internal and external Ca2+ pools to the cell response were determined by studying the hormone mediated [Ca2+]i increase and glycogen phosphorylase activation in low-Ca2+ media (22 microM). In this medium: (1) [Ca2+]i was lowered and the hormones initiated a transient instead of a sustained increase in [Ca2+]i; subsequent addition (2 min) of a second hormone promoted a lesser increase in [Ca2+]i; in contrast, the subsequent addition (2 min) of Ca2+ (1.8 mM) caused [Ca2+]i to increase to a value close to that initiated by the hormone in control conditions, the amplitude of the latter response being dependent on the concentration of Ca2+ added to the medium; (2) returning to normal Ca2+ (1.8 mM) restored the resting [Ca2+]i and allowed the hormone added 2 min later to promote a large increase in [Ca2+]i whose final amplitude was also dependent on the concentration of Ca2+ added beforehand. Similar results were found when the same protocol was applied to the glycogen phosphorylase activation. It is concluded that Ca2+ influx is required for a maximal and sustained response and to reload the hormone-sensitive stores. PMID- 4026799 TI - Removal of an N-terminal peptide from mitochondrial aspartate aminotransferase abolishes its interactions with mitochondria in vitro. AB - Treatment of mitochondrial aspartate aminotransferase from rat liver with trypsin leads to specific cleavage of the bonds between residues 26 and 27, and residues 31 and 32. The proteolysed enzyme has only a small residual catalytic activity, but retains a conformation similar to that of the native form as judged by accessibility and reactivity of cysteine residues. Proteolysis abolishes the ability of the enzyme either to bind to mitochondria or to be imported into the organelles. This suggests that the N-terminal segment of the native enzyme is essential for both of these functions, at least in the model system used to study the import process. PMID- 4026800 TI - Studies of the limited degradation of mucus glycoproteins. The mechanism of the peroxide reaction. AB - The reaction between ovarian-cyst glycoproteins and H2O2 was investigated in the presence of a number of inhibitors and catalysts. Azide and 2H2O were separately found to have little effect, implying that singlet oxygen was not involved. Superoxide dismutase was destroyed by H2O2, but mannitol had no effect: thus generalized attack by OH., whether originating from HO2.- or more directly, is not indicated. The glycoproteins contained trace quantities of Cu and Fe, amounting to about 2 atoms of metal per glycoprotein molecule. Treatment of the glycoproteins with the strong chelator DETAPAC (diethylenetriaminepenta-acetic acid) or Chelex resin eliminated the reaction with H2O2; activity could be restored by addition of Cu2+ or Fe2+ in millimolar quantities. It was concluded that metal-ion catalysis is an essential step in the attack of H2O2 on glycoproteins. Spectroscopic and other evidence showed that Cu2+ (and probably Fe2+) complexes strongly with poly-L-histidine, and implies that the Cu2+ or Fe2+ in the glycoproteins is complexed with some of the histidine residues in the glycosylated backbone. Neither polyhistidine nor polyproline reacted with H2O2 in the absence of metal ions, but small quantities of Cu2+ or Fe3+ caused degradation. This was rapid with polyhistidine, which was converted largely into aspartic acid, but slower with polyproline, where limited conversion into glutamic acid occurs. These findings confirm the original hypothesis that peroxide attack on glycoproteins occurs largely at the histidine residues, with simultaneous peptidolysis. The mechanism most probably involves the liberation of OH. by an oxidation-reduction cycle involving, e.g. Cu+/Cu2+: specificity of attack at histidine is due to the location of the metal at these residues only. PMID- 4026801 TI - Characterization of human tissue carnosinase. AB - Human tissue carnosinase (EC 3.4.13.3) had optimum activity at pH9.5 and was a cysteine peptidase, being activated by dithiothreitol and inhibited by p hydroxymercuribenzoate. By optimizing assay conditions, the activity per g of tissue was increased 10-fold compared with values in the literature. The enzyme was present in every human tissue assayed and was entirely different from serum carnosinase. Highly purified tissue carnosinase had a broader specificity than hog kidney carnosinase. Although tissue carnosinase was very strongly inhibited by bestatin, it did not hydrolyse tripeptides, and thus appears to be a dipeptidase rather than an aminopeptidase. It had a relative molecular mass of 90 000, an isoelectric point of 5.6, and a Km value of 10 mM-carnosine. Two forms of kidney and brain carnosinase were separated by high-resolution anion-exchange chromatography, although only one form was detected by various electrophoretic methods. Homocarnosinase and Mn2+-independent carnosinase were not detected in human tissues, although these enzymes are present in rat and hog kidney. PMID- 4026802 TI - Selective reduction of a disulphide bridge in hen ovotransferrin. AB - Brief treatment of iron-saturated hen ovotransferrin with dithiothreitol selectively cleaves the disulphide bridge between residues 478 and 671, which is in the C-terminal domain of the protein. The reduced alkylated protein is less stable than the native protein, and its iron-binding properties are different. A fluorescent derivative was prepared by coupling N-iodoacetyl-N'-(5-sulpho-1 naphthyl)ethylenediamine to the thiol groups. PMID- 4026803 TI - Phosphatidylglycerol as biosynthetic precursor for the poly(glycerol phosphate) backbone of bifidobacterial lipoteichoic acid. AB - Phosphatidylglycerol functions as donor of the sn-glycerol 1-phosphate units in the synthesis in vitro of the 1,2-phosphodiester-linked glycerol phosphate backbone of the lipoteichoic acids of Bifidobacterium bifidum subsp. pennsylvanicum. The incorporation was catalysed by a membrane-bound enzyme system. After addition of chloroform/methanol the product formed coprecipitated with protein. The material was phenol-extractable and was co-eluted with purified lipoteichoic acid on Sepharose 6B. The reaction was stimulated by Triton X-100, UDP-glucose and UDP-galactose, but Mg2+ ions had no effect. The apparent values for Km and Vmax. of the phosphatidylglycerol incorporation were 1.4 mM and 3.1 nmol/h per mg of membrane protein, respectively. Labelled UDP-glucose and UDP galactose were not incorporated into the lipoteichoic acid fraction by the particulate membrane preparation. PMID- 4026804 TI - Decreased ovalbumin-gene response to oestrogen in the prenatally diethylstilboestrol-exposed chick oviduct. AB - Prenatal exposure of the female chick-embryo Mullerian duct to diethylstilboestrol (DES) decreases its future capacity for epithelial tubular gland-cell differentiation and oviduct ovalbumin-gene expression. Chick Mullerian ducts after prenatal exposure to different concentrations of DES were tested after birth to determine the response of the oviduct toward the oestrogen induction. The quantity of DNA was biochemically determined, the differentiation of tubular-gland cells in the oviduct was studied by light microscopy, and the expression of the ovalbumin gene was detected by hybridization of the total RNA with radioactive ovalbumin cDNA. Comparisons among these three parameters revealed that the expression of the ovalbumin gene was affected most by DES exposure. Exposure to high doses of DES suppressed ovalbumin-gene expression by 75-78%, and inhibited tubular-gland-cell differentiation and thus decreased the DNA content by 29 and 32% respectively. Exposure to low doses of DES caused suppression of ovalbumin-gene expression by 47-53%, but it did not affect the other two parameters. Prenatal DES exposure has strong inhibitory effects on the Mullerian duct at the age (5-8-day-old embryos) when the organ is undifferentiated. Less inhibition is observed when the organ becomes differentiated (15-day-old embryos and older). PMID- 4026805 TI - Sidedness studies of thylakoid phosphatidylglycerol in higher plants. AB - The transmembrane distribution of phosphatidylglycerol was determined in thylakoids from barley (Hordeum vulgare), lettuce (Lactuca sativa) and pea (Pisum sativum) chloroplasts. Phospholipase A2 and phospholipase D digestion and chemical-labelling methods were used. Phosphatidylglycerol was preferentially localized in the outer (stromal) leaflet. The proportion of the phospholipid in this leaflet ranged from about 66% in pea to about 75% for barley and lettuce thylakoids. One of the main fatty acids, trans-delta 3-hexadecenoic acid, was exclusively located in the outer leaflet in all three plant types. The data are discussed in relation to suggested roles for phosphatidylglycerol in thylakoid function. PMID- 4026806 TI - Evidence that the stimulation of lipogenesis in the mammary glands of starved lactating rats re-fed with a chow diet is dependent on continued hepatic gluconeogenesis during the absorptive period. Effects of a gluconeogenic inhibitory, mercaptopicolinic acid, in vivo. AB - The rapid stimulation of lipogenesis in mammary gland that occurs on re-feeding starved lactating rats with a chow diet was decreased (60%) by injection of mercaptopicolinic acid, an inhibitor of hepatic gluconeogenesis at the phosphoenolpyruvate carboxykinase step. Mercaptopicolinate had no effect on lipogenesis in mammary glands of fed lactating rats. The inhibition of lipogenesis persisted in vitro when acini from mammary glands of re-fed rats treated with mercaptopicolinate were incubated with [1-14C]glucose. Mercaptopicolinate added in vitro had no significant effect on lipogenesis in acini from starved-re-fed lactating rats. Mercaptopicolinate prevented the deposition of glycogen and increased the rate of lipogenesis in livers of starved re-fed lactating rats, whereas it had no significant effect on livers of fed lactating rats. Administration of intraperitoneal glucose restored the rate of mammary-gland lipogenesis in re-fed rats treated with mercaptopicolinate to the values for re-fed rats. Hepatic glycogen deposition was also restored, and the rate of hepatic lipogenesis was stimulated 5-fold. It is concluded that stimulation of mammary-gland lipogenesis on re-feeding with a chow diet after a period of starvation is in part dependent on continued hepatic gluconeogenesis during the absorptive period. Possible sources of the glucose precursors are discussed. PMID- 4026808 TI - Halistaurin, phialidin and modified forms of aequorin as Ca2+ indicator in biological systems. AB - Two kinds of aequorin-type photoproteins, i.e., halistaurin and phialidin, and four kinds of modified forms of aequorin, i.e., products of acetylation, ethoxycarbonylation, fluorescamine-modification and fluorescein labelling, were prepared. The modified forms of aequorin were more sensitive to Ca2+ than was aequorin in their Ca2+-triggered luminescence reactions, whereas halistaurin and phialidin were less sensitive. The emission maxima of luminescence were all within a wavelength range 450-464 nm, except for fluorescein-labelled aequorin, which emitted yellowish light (lambda max. 520 nm). A new technique of measuring Ca2+ concentration is suggested. PMID- 4026807 TI - Thromboplastin (tissue factor) in plasma membranes of human monocytes. AB - The synthesis of thromboplastin, a potent trigger of blood coagulation, can be induced in human peripheral blood monocytes. Indirect evidence suggests that newly synthesized thromboplastin becomes in part available on the cell surface. We have attempted to study the localization and availability of thromboplastin more directly by isolating plasma membranes from isolated human peripheral blood monocytes. The specific activities of the plasma membrane markers increased 16-22 fold in these preparations with a recovery of about 15%. The contamination by mitochondria, lysosomes, nuclei and endoplasmic reticulum was low as estimated by marker enzymes and electron microscopy. In both unstimulated and stimulated monocytes thromboplastin was largely recovered in this plasma membrane fraction, providing direct evidence for its membrane localization. Phospholipase C (E.C. 3.1.4.3) is a potent inactivator of thromboplastin through its hydrolysis of the phospholipids necessary for thromboplastin activity [Otnaess, Prydz, Bjorklid & Berre (1972) Eur. J. Biochem. 27, 238-243]. About 70% of the total membrane thromboplastin activity was inactivated when whole cells were treated with phospholipase C and the membranes subsequently isolated. Following stimulation to induce thromboplastin synthesis, the plasma membranes showed a shift in their relative content of phosphatidylcholine and phosphatidylethanolamine consistent with a transmethylation process. PMID- 4026809 TI - High concentrations of aldehydes slow the reaction of cytoplasmic aldehyde dehydrogenase with thiol-group modifiers. AB - High concentrations of aldehydes slow the inactivation of cytoplasmic aldehyde dehydrogenase by disulfiram and also slow the reaction of the enzyme with 2,2' dithiodipyridine. It is concluded that a low-affinity aldehyde-binding site is probably the site at which thiol-group modifiers react with aldehyde dehydrogenase, as well as being the active site for hydrolysis of 4-nitrophenyl acetate. PMID- 4026810 TI - A novel hopanoid, 30-(5'-adenosyl)hopane, from the purple non-sulphur bacterium Rhodopseudomonas acidophila, with possible DNA interactions. AB - A novel hopanoid, 30-(5'-adenosyl)hopane, was isolated from the purple non sulphur bacterium Rhodopseudomonas acidophila and identified. The significance of this triterpenoid in terms of bacteriohopanepolyol biosynthesis, membrane reinforcement and possible interactions with nucleic acids is discussed. PMID- 4026811 TI - Dopamine stimulated fucosylation of rat hippocampal proteins in vitro. A histoautoradiographic study. AB - The aim of the present investigation was to provide evidence for the topographic localization of dopamine (0.5 mM) stimulated L-[3H]fucose incorporation into rat hippocampal proteins in vitro. For this purpose, radiochemical estimations of fucosylation of hippocampal proteins were paralleled by histoautoradiography. The data of the radiochemical study showed a dopamine induced increase in L [3H]fucose incorporation into hippocampal proteins by about + 120% compared to control values. Hippocampus slices from the same animals were processed for histoautoradiography. Under the influence of dopamine, L-[3H]fucose incorporation (estimated as silver grains either per cell or per square) was found to be significantly elevated in pericarya of granular cells as well as in the neuropil and in the glial cells of the stratum moleculare of the exposed blade of dentate area. This increase was most pronounced in the pericarya of granular cells, i.e. by about 200% over control level. With exception of fibres in the stratum lacunosum-moleculare of CA 1, the trends of increase in neurons, glial cells and fibre layers of other hippocampus subfields were not significant. The results may suggest that in rat hippocampus slices, dopamine induced increases in L-fucose incorporation are particularly localized in neurons of the exposed blade of dentate area. PMID- 4026812 TI - Studies of calcium phosphate formation in artificial matrices. AB - An in vitro system is described allowing turbidimetric measurements of calcium phosphates (or other sparingly soluble salts) formed by one-dimensional double diffusion in an agar gel matrix. The basic conditions were investigated over a wide concentration range of calcium and phosphate, and characterized by IR spectra, transmission electron microscopy and selected parameters of the turbidity curve, i.e. the maximal turbidity, the life time of the amorphous calcium phosphate, the optical dispersion and the crystallization rate. The system was also applied to well known effectors, like F-, Mg2+, pyrophosphate and citrate ions as well as two compounds of biological matrices, hyaluronidate and chondroitin-4-sulphate. The results agree well with those observed in aqueous solutions, showing that the overall process in the gel matrix is identical. The economical and efficient method is suitable for large-scale kinetic determinations of compounds affecting nucleation, precipitation and transformation processes of calcium phosphates and other precipitating systems. PMID- 4026814 TI - [The effect of various ventilation conditions on evoked potentials of the visual cortex of the cat in distention of the stomach]. AB - In 10 cats anaesthetized using chloralose and with muscular relaxation by gallamine and continuous artificial ventilation in acute experiments photically evoked potentials (PEP) were recorded from the visual area of the cortex under different intragastric pressures and varying tidal volumes. It was the aim of this study to examine whether an exteroceptive stimulus (light flash) in the visual analyzer, which is influenced by an interoceptive stimulation (gastric pressure), may also be modified by different tidal volumes. Times, amplitudes and slope parameters, blood pressure and heart rate of the animals were studied. The PEP of the visual cortex was modified under the influence of the interoceptive stimuli. It could, however, be shown that already hypo- and hyperventilation alone may cause alterations in the latency period of the PEP. They arise in a different manner in individual parts of the measured parameters of the PEP and do not change these values in a typical manner. Additional dilatation of the stomach may suppress the phenomena caused by alterations in the tidal volume. Thus, attention should be paid to both blood gases and acid base balance in animals in studies on viscero-cerebral interrelationships as well as to interactions between different analyses using the method of evoked potentials. PMID- 4026813 TI - Chicken fetal intestine in tissue culture. AB - A simple and reproducible method for cultivation of fetal chicken small intestine is presented. The culture was performed in a defined medium without serum. Duodena were excised from embryos at the 14th day of fetal development and cut in small segments that were maintained in culture until day 16. It could be shown that the morphology of cultured intestine resembles that of noncultured gut of corresponding age as judged by light microscopy. The increase in activity of sucrase and maltase in cultured explants is comparable with that of intestine in ovo, whereas that of alkaline phosphatase is lower than under in vivo conditions. Hormones (thyroxine, dexamethasone) influence the enzymic pattern of fetal intestine in a known manner. Therefore, the method permits maintenance of fetal intestine in tissue culture for 2 days, a period sufficient for investigation of maturation processes of intestinal mucosa. PMID- 4026815 TI - Effect of propranolol on lecithin:cholesterol acyl transferase activity in vitro. AB - Recently propranolol was found to inhibit human lecithin: cholesterol acyl transferase (LCAT) activity both after oral treatment and after addition to plasma in vitro. Now the dose-response relationship of the propranolol effect on LCAT activity was evaluated in vitro. Concentrations required to produce half maximal effects in 7 men ranged from 32.4 to 121.4 nmol/l which corresponds to the therapeutical concentration range of the drug. Complete inhibition could not be achieved. The maximal effect (propranolol-sensitive LCAT activity) varied between subjects depending on the preexiting lecithin: cholesterol acyl transfer rate in plasma. Propranolol mediated inhibition of LCAT activity could be abolished when heat-inactivated plasma instead of native plasma was used as LCAT substrate. It is concluded that the interindividual variability of propranolol sensitive LCAT activity may reflect differences in the thermoinstable lipoprotein structure. PMID- 4026816 TI - Effects of D-galactosamine and D-glucosamine on retention performance of a brightness discrimination task in rats. AB - The glycoprotein and ganglioside precursors D-galactosamine and D-glucosamine were tested for effects on acquisition and retention of a brightness discrimination reaction in rats. Intraperitoneally (1.85 mmoles/kg) and intraventricularly (0.8 mumoles) applied D-galactosamine had no influence on acquisition, but improved the retention performance. Intraperitoneally (6.0 mmoles/kg) and intraventricularly (2.4 mumoles) applied D-glucosamine showed qualitatively identical results, i.e. improving effect on retention performance. The penetration abilities of [3H]D-glucosamine and [3H]N-acetyl-D-glucosamine to cross the blood-brain barrier were tested: D-glucosamine penetrated easily the blood-brain barrier (approximately 2:1 relation). However, after intravenous application of 200 mumoles 30 min before training both substances showed a positive effect on retention performance. The findings are discussed in the light that the retention-improving effects of the hexosamines under investigation are believed to be due to a direct, activating influence on glycoprotein and/or ganglioside syntheses in the brain. PMID- 4026817 TI - [The effect of the systemic and intraventricular application of orotic acid on monosynaptic evoked potentials in the dentate gyrus in free-moving rats]. AB - In 20 freely moving Wistar rats the influence of systemically and intraventricularly applied orotic acid derivatives on monosynaptically evoked field potentials registered in the dentate gyrus on the stimulation of the medial entorhinal cortex was investigated. Both, methylglucamine-orotate and tris orotate led to an increase of the amplitude of the population spike. The slope function of the field EPSP, however, remained unchanged. The effect has been observed to begin 2 h after application and had a duration of 6-10 h. The data obtained in a monosynaptic pathway targeting on a brain structure which is known to play a crucial role in memory formation support earlier findings of a transient effect of orotic acid on cerebral excitation processes. An influence on mechanisms of spike generation or other postsynaptic membrane processes might be assumed. PMID- 4026818 TI - [Facilitation of evoked transcallosal responses by nootropic agents]. AB - The effect of nootropic drugs was investigated by studying their influences on transcallosal responses in rats. Piracetam, meclofenoxate, vinpocetin, pyritinol, orotic acid and dihydroergotoxine as well as its components dihydroergocornine and dihydroergocrytpine enhance in a dose dependent manner the amplitudes of transcallosal responses. The evoked potentials remain unchanged after dihydroergocristine and nicergoline by the dosage used. PMID- 4026819 TI - [The problem of the characterization of butoxamine as a specific antagonist of the metabolic effects of sympathomimetics]. PMID- 4026820 TI - The analgesically effective peptide deprolorphin exhibits cross-tolerance to morphine in rats. AB - The potent analgesically active beta-casomorphin derivative, D-Pro4-beta casomorphin 1-5 (= Deprolorphin), was tested for its capacity to induce tolerance. In animals tolerant to morphine, a previously analgesically effective test dose of the peptide was without any antinocipetive effect, demonstrating a cross-tolerance between morphine and deprolorphin. PMID- 4026821 TI - Isolation and partial characterization of a novel basement membrane collagen. AB - A guanidine-HCl extraction of lens capsule basement membrane dissolves collagenous material. This material was fractionated on an Agarose A-5M column. Fractions 1, 2 and 3 were further purified and partially characterized immunochemically and by amino acid analysis. Fraction 3 has a molecular weight of 55,000 when compared with collagen type I standard. The CNBr peptide pattern and composition of fraction 3 are different from those of alpha 1 (IV) 95K and alpha 2 (IV) 95K chains. The results described suggest the presence of a new chain in lens capsule basement membrane. PMID- 4026822 TI - Increased rate of superoxide ion generation in Fanconi anemia erythrocytes. AB - The rate of generation of superoxide ion, the concentration of Cu, Zn superoxide dismutase and the hematological parameters were measured in red blood cells obtained from Fanconi anemia patients and from healthy individuals. No significative difference in the superoxide dismutase concentration was found, while the rate of generation of the superoxide ion doubled in Fanconi anemia patients. The steady-state concentration of the superoxide ion was calculated from these data and was found to be 2.3 times higher in Fanconi anemia erythrocytes than in controls. The possible consequences with respect to the alterations in FA are discussed. PMID- 4026823 TI - N-ethylmaleimide causes mechanical fragility and accumulation of spectrin dimers in the rat erythrocyte membrane. AB - Treatment of rat erythrocytes with N-ethylmaleimide is found to render them mechanically fragile. Membranes of the lysed cells show degradation of band 3 and, to a lesser extent, of spectrin; as well as considerable accumulation of dimeric spectrin. The predominant action of N-ethylmaleimide on isolated membranes, however, is the conversion of spectrin to its dimeric form. PMID- 4026824 TI - Post-illumination kinetics of cytochrome f reduction in chloroplast thylakoid in the presence of dibromothymoquinone. AB - Addition of dibromothymoquinone (DBMIB) to isolated chloroplast thylakoids reduces cytochrome f in the dark. Reduced cytochrome f is oxidised when the thylakoids are illuminated, and is re-reduced in the subsequent darkness. The rate of re-reduction in the dark is faster after red (650 nm) illumination than after far red (713 nm) illumination. In the presence of DCMU or upon heat treatment or at high (greater than 10 microM) concentration of DBMIB the rate of dark reduction after red illumination becomes slower and equal to that after far red illumination, suggesting that photosystem II electron transfer at least upto plastoquinone facilitates DBMIB-mediated reduction of cytochrome f in the thylakoids. PMID- 4026825 TI - Conformational alteration in alpha-toxin from Staphylococcus aureus concomitant with the transformation of the water-soluble monomer to the membrane oligomer. AB - The membrane-damaging alpha-toxin aggregate of Staphylococcus aureus was characterized physicochemically. The aggregate weight of the toxin formed by various methods appeared to be 6 times higher than the molecular weight of the monomer as determined by the laser light scattering technique, suggesting the presence of a hexamer in the membrane. The aggregates fluoresced 20 to 50% more than the monomer at 336 nm. Circular dichroism measurements revealed that both the monomer and the oligomer showed essentially beta-sheet structure with the maximum ellipticity about -8,400 deg.cm2.dmol-1 at 215 nm. Circular dichroism spectrum of the oligomers showed ellipticity difference of -6,600, -44 and +84 deg.cm2.dmol-1, at 200, 250 and 280 nm, respectively, compared with the monomer. All these results suggest that the conformational change in the toxin molecule occurs concomitant with the transformation of the water-soluble monomer to the membrane-embedded hexamer. PMID- 4026826 TI - Defective cold-induced stimulation of thyroxine 5'-deiodinase in brown adipose tissue of the genetically obese (ob/ob) mouse. AB - Exposure of a normal lean mouse to cold (14 degrees C) for 12 h increases the activity of thyroxine 5'-deiodinase in brown adipose tissue 26-fold. In contrast, exposure of the genetically obese, ob/ob, mouse to cold results in little more than a doubling of thyroxine 5'-deiodinase activity. The physiological significance of endogenous 3,5,3'-triiodothyronine production in brown adipose tissue is not understood. However, it seems likely that defective cold-induced stimulation of the 5'-deiodinase in brown adipose tissue of the ob/ob mouse might cause a relatively hypothyroid state of the tissue. Thyroid hormone is known to be required for a normal thermogenic response of brown adipose tissue to noradrenaline. It is suggested that the defect in the response of the 5' deiodinase in the ob/ob mouse could contribute to the defective thermogenic response of brown adipose tissue to cold-exposure and to noradrenaline. PMID- 4026827 TI - The effect of ferric iron complex on Ca2+ transport in isolated rat liver mitochondria. AB - The in vitro effects of iron (III)-gluconate complex on the production of malondialdehyde and on the Ca2+ transport in isolated rat liver mitochondria were studied. A correlation between the concentration of iron added and the formation of malondialdehyde was found. The enhancement by iron of lipid peroxidative process in the mitochondrial membrane brought about the induction of Ca2+ release from mitochondria. Experimental evidence based on the membrane potential pattern of mitochondria pre-loaded with a low pulse of Ca2+ suggested that Ca2+ efflux was not due to a nonspecific increase in the inner membrane permeability, i.e. to a collapse of membrane potential, but rather to the activation of an apparently selective pathway for Ca2+ release. PMID- 4026828 TI - Possible role for carbamyl phosphate in the control of liver glycogen synthesis. AB - Isotopic data suggested a possible correlation between the activation of liver glycogen synthesis and some unstable intermediate. Carbamyl phosphate was one candidate considered. L-Norvaline, an inhibitor of ornithine transcarbamylase, is known to increase intracellular carbamyl phosphate levels. L-Norvaline augmented the increase in glycogen synthesis caused by L-glutamine and L-alanine, and also induced considerable glycogen synthesis with ammonia as the nitrogen source. PMID- 4026829 TI - Brown adipose tissue is a major site of glucose utilisation in C57Bl/6 ob/ob mice treated with a thermogenic beta-adrenoceptor agonist. AB - Chronic treatment of C57Bl/6 ob/ob mice with the thermogenic beta-adrenoceptor agonist BRL 26830 increased the maximal activities of hexokinase and phosphofructokinase 2- and 3-fold respectively in interscapular brown adipose tissue. Combining measurements of whole body glucose turnover with measurements of the uptake of 2-deoxyglucose by tissues in vivo has allowed tissue rates of glucose utilisation to be calculated. Under basal conditions, brown adipose tissue accounts for only 1.6% of the whole body rate of glucose utilisation. This is increased to 3.7% in mice given a single dose of BRL 26830. In ob/ob mice treated chronically with BRL 26830, which causes brown adipose tissue hypertrophy, glucose utilisation by this tissue was increased to 4.1% of the whole body rate under the basal condition. In these mice, an additional acute treatment with BRL 26830 increased brown adipose tissue glucose utilisation rate to 12.5% of the whole body rate. PMID- 4026830 TI - Inhibition of initiation of simian virus 40 chromosome synthesis by dihydroxyanthraquinone. AB - The mode of action of dihydroxyanthraquinone, a new antitumor drug, on eucaryotic chromosome structure and function was investigated using simian virus 40 as a model system. Dihydroxyanthraquinone specifically inhibited initiation of viral replicons. Little or no viral DNA synthesis was recovered in cells after the removal of the drug. Elongation and termination of DNA already initiated could proceed continuously to completion in drug-treated cells. The drug appeared to be stably associated with viral chromosomes in cells. The irreversible inhibition of replicon initiation might contribute to its anti-proliferative and anti neoplastic activity. PMID- 4026831 TI - Isolation of a protein from human milk that enhances zinc absorption in humans. AB - Humans absorb zinc more readily from human milk than from the milk of other species. The basis for this species specificity has not been elucidated. This report describes the isolation of a human milk protein which enhances zinc absorption. The consumption of bovine cow's milk supplemented with the human protein resulted in an elevation in human plasma zinc of 101% compared to a 50% rise following the ingestion of cow's milk alone. The identification of this biologically active protein in human milk establishes in part the basis for the species difference in zinc bioavailability. PMID- 4026832 TI - Inositol-1,4,5-trisphosphate releases calcium from skinned cultured smooth muscle cells. AB - We examined the effects of inositol-1,4,5-trisphosphate on 45Ca uptake and 45Ca efflux in the saponin skinned primary cultured rat aortic smooth muscle cells. 10 microM inositol-1,4,5-trisphosphate induced a rapid (half time less than 10 sec) and large quantity of Ca release in both 45Ca uptake and 45Ca efflux in the skinned cells preloaded with 1 microM free Ca. Dose response curves showed that 100 microM inositol-1,4,5-trisphosphate produced a maximal Ca release of 97.3% of the MgATP dependent 45Ca uptake or 289 mumoles/liter cells, which was much greater than the maximal caffeine induced Ca release and would be sufficient to produce maximal tension. PMID- 4026833 TI - Degree of conservation of HeLa interphase nonhistone antigens in metaphase and with chromatin from non-human cells. AB - Immunological procedures were applied to determine the degree of conservation of the nonhistone proteins of HeLa interphase chromatin. Polyacrylamide gels were overlaid with antiserum to HeLa interphase chromatin, and 125I-Protein A was used to detect bound antibodies. With two-dimensional gels, more than 80 interphase species were found as components of metaphase chromosomes. The degree of conservation of HeLa nonhistone antigens with other chromatin sources was calculated through densitometry of autoradiograms and stained gels. Chromatin was obtained from chicken erythrocytes, Novikoff rat hepatoma cells, and mouse L cells, and the presence of one-quarter to one-third of the nonhistone antigens of HeLa chromatin was demonstrated. PMID- 4026834 TI - The effect of metalloporphyrins and heme liposomes on delta-aminolevulinate synthase activity in rat liver. AB - Heme administration causes inhibition of delta-aminolevulinate synthase (ALAS), best tested in the allylisopropylacetamide (AIA)-treated rat, a model for hepatic porphyrias. Because heme suspended in aqueous media (for injection) is unstable and has adverse effects on coagulation, alternate therapeutic modalities are being explored. The present study tries to answer two questions: 1) are any heme analogs as effective inhibitors of ALAS as heme is; and 2) does heme administration in the form of liposomes increase its effectiveness? None of the liposome compositions tested, even if containing lactosylceramide for preferential hepatocyte uptake, was more effective in inhibiting AIA-induced ALAS activity than heme in buffer. As for the function of the heme analogs, although deuteroheme and heme dimethyl ester proved ineffective, mesoheme and cobalt protoporphyrin were nearly as effective as heme itself, indicating that both hydrophobic side chains in positions 2 and 4 and free propionate groups at 6 and 7 are essential for ALAS inhibition, as is the presence of a central cobalt or iron atom. PMID- 4026835 TI - Identification of urinary metabolites of the nephrotoxic hydrocarbon 2,2,4 trimethylpentane in male rats. AB - The compound 2,2,4-trimethylpentane (2,2,4 TMP) is reported to be especially potent in inducing kidney lesions in male rats (1,2). Although the pathology produced by 2,2,4 TMP has been examined (1), there are no reports concerning the metabolism of 2,2,4 TMP by the male rat. The eight principal urinary metabolites of 2,2,4 TMP found in the urine of Fischer 344 male rats are: 2,2,4-trimethyl-1 pentanol, 2,4,4-trimethyl-1-pentanol, 2,4,4-trimethyl-2-pentanol, 2,2,4-trimethyl 1-pentanoic acid, 2,4,4-trimethyl-1-pentanoic acid, 2,4,4-trimethyl-2-hydroxy-1 pentanoic acid, 2,2,4-trimethyl-5-hydroxy-1-pentanoic acid and 2,4,4-trimethyl-5 hydroxy-1-pentanoic acid. PMID- 4026836 TI - Introduction of the dansyl group into histidine and tyrosine residues in peptides and proteins. AB - Two dansyl derivatives: 1-(5-dimethylaminonaphthalene) sulfonyl (4-amino)-benzyl amine and 1-(5-dimethylaminonaphthalene) sulfonyl beta(4-aminophenyl) ethylamine, have been recently synthesized. Reaction of these compounds with nitrous acid lead to the corresponding dansyl-bearing diazonium salts. The latter derivatives can couple, under mild basic conditions, to the imidazole moiety of histidine, the phenolic ring of tyrosine and to the epsilon-amino function of lysine. The applicability of the two reagents was tested in the modification of several peptides, including [D-Phe6]LHRH, [D-Gln6]LHRH, Leu-enkephalin and Tyr-tuftsin, and proteins such as calmodulin, bovine serum albumin and nerve growth factor. PMID- 4026837 TI - An HPLC/push-pull perfusion technique for investigating peptide metabolism. AB - We have combined the push-pull perfusion of radiolabelled peptide, with reverse phase--HPLC procedures as a valuable method for monitoring peptide metabolism in the CNS. This model not only permits studies on metabolism of neuropeptides at specific sites in the CNS, but more importantly, allows (unlike in vitro methods) the study to be made under the appropriate physiological conditions. We have demonstrated unambiguously for the first time, the metabolism of CCK-8 in situ. PMID- 4026838 TI - A note on Ca2+ binding to calmodulin. AB - Binding of Ca2+ to calmodulin has been simulated on the basis of a model that assumes two classes, two sites in each class, of Ca2+ binding sites. With properly chosen values of binding constants for the two classes of sites, and with the assumption that certain degree of positive cooperativity exists between the two sites in each class, the overall binding isotherm can be generated so that it appears to be a single-transition, non-cooperative binding curve of four equivalent sites. Thus this model offers a resolution for some of the discrepancies among Ca2+ binding studies of calmodulin. PMID- 4026839 TI - Extracellular matrix (ECM) synthesis in muscle cell cultures: quantitative and qualitative studies during myogenesis. AB - When the synthesis of extracellular matrix components was examined in G8-1 murine skeletal muscle cells as a function of differentiation, non-collagen and to an even greater extent collagen synthesis was increased. Specifically, collagen types I, III, IV, laminin and fibronectin were identified by SDS-PAGE. Immunoprecipitation, with specific antibodies revealed that both the cell layer and medium of differentiated multinucleated myotubes contained increased levels of type IV collagen and laminin, decreased levels of type III collagen and fibronectin and equivalent levels of type I collagen compared to mononuclear myoblasts. PMID- 4026840 TI - Reaction of optically active S- and R-forms of dolichyl phosphates with activated sugars. AB - Chemical synthesis was used to produce optically active isomers of dolichol (S- and R-forms) with 18 and 19 isoprene residues. The phosphorylated polyprene was studied in rat liver microsomal GDP-mannosyl and UDP-N-acetylglucosaminyl transferase systems. The two dolichol-P forms in both transferase systems gave Vmax values which for the S-form exceeded 4-6 times what was obtained with the R form. The Km values were also higher for the S-form. The hepatocyte appears to contain a large excess of dolichyl-P, by 100 times exceeding that of the Km values. For this reason the S-form of dolichyl-P seems to be one of the requirements for the normal establishment of the N-glycosidically linked oligosaccharide chain. PMID- 4026841 TI - Measurement of immunoreactive leukotriene C4 in blood of asthmatic children. AB - Peptide leukotriene (LT) such as LTC4, LTD4, LTE4 have been considered to be major mediators of immediate type hypersensitivity reaction such as asthma. We have developed a rapid and simple extraction method using a Sep-Pak C18 cartridge for the measurement of LTC4 by radioimmunoassay (i-LTC4). In this extraction method, 91% LTC4 was recovered in a final methanol fraction. The identity was confirmed by the recovery test and by the dilution method. The amount of i-LTC4 in plasma from asthmatic patients was determined by radioimmunoassay after the extraction. The order of the plasma level of i-LTC4 was; severe asthma greater than slight or moderate asthma greater than asthmatic patient without attack greater than healthy adult. The highest level of LTC4 was 0.27 +/- 0.11 pmol/ml in severe asthmatic plasma. PMID- 4026842 TI - Band 3 protein of the red cell membrane of the llama: crosslinking and cleavage of the cytoplasmic domain. AB - Comparative studies were done on the cytoplasmic domain of the band 3 protein in the red cell membranes of the the human and the llama. Two approaches were used: crosslinking with o-phenanthroline/CuSO4, and cleavage with 2-nitro-5 thiocyanobenzoate. o-Phenanthroline/CuSO4 crosslinks the band 3 polypeptide chains in the human; in contrast band 3 in the llama is minimally crosslinked by this agent. 2-Nitro-5-thiocyanobenzoate cleaves band 3 in the human into a 23,000 dalton fragment; a similar fragment is not generated from the llama band 3. These studies show that the cysteine residue located 23,000 daltons from the N-terminus of band 3 in the human involved in these reactions is unavailable for crosslinking and cleavage in the llama. Species differences in the cytoplasmic domain of band 3 may contribute to the unusual resistance of llama red cells to osmotic, chemical and physically-induced deformation. PMID- 4026843 TI - Polypentapeptide of elastin: temperature dependence of ellipticity and correlation with elastomeric force. AB - Circular dichroism (CD) is used to follow the conformational changes that attend temperature dependent aggregation leading to the viscoelastic (coacervate) state of the polypentapeptide of elastin in water. Two concentrations are used, 2.3 mg/ml and 0.023 mg/ml. The former results in aggregates of a size that exhibit much particulate distortion of the CD spectra whereas the latter results in spectra that are relatively free of distortions. Given the CD spectra of the temperature dependent aggregation of the lower concentration, it is possible to show that the same conformational change is occurring at high concentration. The structure of the polypentapeptide is one of limited order below 20 degrees C which undergoes an inverse temperature transition to a conformation characterized by a regularly recurring beta-turn at 40 degrees C. The temperature profile for the conformational change is compared to the temperature dependence of elastomeric force of gamma-irradiation cross-linked polypentapeptide coacervate. The curves virtually superimpose. When there is little order, there is little elastomeric force and elastomeric force develops to a near maximal value as the repeating Type II beta-turn conformation develops. Not only is the elastomeric state non-random, the more nearly random state has very little elasticity. These results are the inverse of expectations based on the classical theory of rubber elasticity. PMID- 4026844 TI - Enantioselectivity in glutathione conjugation of 1,2-epoxy-1,2,3,4 tetrahydronaphthalene by hepatic glutathione S-transferase. AB - Enantiomers of 1,2-epoxy-1,2,3,4-tetrahydronaphthalene (ETN) were conjugated with glutathione (GSH) specifically at their benzylic oxiran carbons, with a marked difference in rate [(1R,2S)-(+)- less than (1S,2R)-(-)-ETNs] as well as in affinity for GSH S-transferase [Km: (1S,2R)-(-)- less than (1R, 2S)-(+)-ETNs], in rat liver cytosol to yield two diastereomeric S-(2-hydroxy-1,2,3,4 tetrahydronaphth-1-yl)glutathiones which were separable by reverse partition hplc. Enzymatic GSH conjugation of racemic ETN occurred preferentially with the (1S,2R)-(-)-component as a result of its retarding effect on the conjugation of the (1R,2S)-(+)-counterpart, one half of which remained in enantiomerically pure form in the incubation medium when the (1S,2R)-(-)-component had been completely conjugated. PMID- 4026845 TI - Identification of the 11,12-dihydro-11,12-dihydroxybenzo(a)pyrene as a major metabolite produced by the green alga, Selenastrum capricornutum. AB - Benzo(a)pyrene metabolites were isolated after incubation of [14C]-benzo(a)pyrene with the green alga, Selenastrum capricornutum. A significant amount of radioactivity chromatographed in the dihydrodiol region which did not coelute with any of the previously identified dihydrodiol metabolites isolated from this system. Following characterization by mass spectrometry, fluorescence spectroscopy, and high pressure liquid chromatography, this metabolite was identified as the cis-11,12-dihydro-11,12-dihydroxybenzo(a)pyrene. This metabolite has not been identified previously as a metabolite formed in a plant system. PMID- 4026846 TI - Protein fingerprint by fast atom bombardment mass spectrometry: characterization of normal and variant human haemoglobins. AB - A procedure using fast atom bombardment mass spectrometry was developed for mapping the proteolytic digest of proteins. The procedure was successfully applied to the tryptic peptides of the human beta-globin chain. Almost all the expected peptides were identified by direct analysis of the peptide mixture on the mass spectrometer. Peptide recognition along the beta-globin chain sequence was easily made on the basis of their molecular weight. The general applicability of this mapping procedure in the analysis of haemoglobinopathies was demonstrated by its use for the structural characterization of a variant beta-globin chain. PMID- 4026847 TI - Sequential homologies between procarboxypeptidases A and B from porcine pancreas. AB - Automated Edman degradation of monomeric procarboxypeptidases A and B from porcine pancreas shows that their N-terminal regions (from residue 1 to 34-37) present a high degree of sequential homology to each other as well as to other related procarboxypeptidases. Conformational predictions based on these sequences confirm their structural homology and indicate the probable existence of two beta turns, one beta-chain and a long alpha-helix in them. On the other hand, tryptic peptide maps on a reverse-phase column indicate great sequential similarities (if not identity) between monomeric procarboxypeptidase A and the procarboxypeptidase A subunit isolated from its binary complex with proproteinase E. PMID- 4026848 TI - Amplified DNA sequences in cancers. AB - Amplification of genes other than known oncogenes was analyzed using an in-gel DNA renaturation method, in which a mixture of restriction fragments of radioactively labelled tracer DNA and unlabelled driver DNA was electrophoresed and amplified DNA fragments were visualized after two cycles of denaturation and renaturation in the gel. Different DNA fragments were found to be amplified more than 400 fold in NB1, a neuroblastoma cell line, in Y79, a retinoblastoma cell line and in H69, a small cell lung carcinoma cell line, in addition to 120 to 160 fold amplification of N-myc gene in these three cell lines. PMID- 4026849 TI - Quantitative analysis of lymphocyte-Salmonella interaction and effect of lymphocyte irradiation by Helium-Neon laser. AB - A model system has been developed to quantitatively investigate bacteria-cell interaction using a rough mutant of Salmonella and human peripheral blood lymphocytes. The effect of lymphocyte irradiation by low-power continuous wave Helium-Neon laser has been investigated since laser therapy in wound and decoubitous ulcer healing could involve the lymphoid cell function. Helium-Neon laser irradiation is shown here to enhance the adherence of Salmonella to lymphocytes. In particular, changes in newly defined binding parameters show that laser irradiation increases the frequency of binding-lymphocytes, the affinity of Salmonella for lymphocytes and the number of lymphocyte receptor sites as well. PMID- 4026851 TI - Loss of calmodulin activity in cardiac sarcoplasmic reticulum after ischemia. AB - Experiments were designed to evaluate whether cardiac ischemia affected the subcellular distribution of calmodulin activity. Major cellular fractions (nuclei, mitochondria, sarcoplasmic reticulum and cytosol) were isolated from globally ischemic hearts by differential centrifugation. Ischemia did not affect calmodulin activity in cell fractions other than sarcoplasmic reticulum, which showed a consistent and complete loss of activity. This site-specific loss of calmodulin activity may be one mechanism by which ischemia induces contractile dysfunction. PMID- 4026850 TI - Inhibitory effects of selenium on the growth of DU-145 human prostate carcinoma cells in vitro. AB - The growth of DU-145 human prostate carcinoma cells is reduced to 50% of control by 1 X 10(-6) M to 2 X 10(-6) M selenium and to 2% of control at 10(-4)M selenium. These cells show greater sensitivity to inhibition of growth or DNA synthesis by selenium than human W1-38 and HeLa cells and mouse mammary tumor cells. It has been shown that selenium inhibits carcinogenesis and reduces the incidence of chemical carcinogen and virus-induced tumors of a variety of organs in animals. Selenium may also inhibit the growth of certain tumor cells of non human origin. To our knowledge, this is the first study on the effects of selenium on the growth of human tumor cells. From extrapolation, it is deduced that selenium serum levels in humans living in high selenium areas may be as high as 10(-6) M and could be effective in inhibiting the growth of tumor cells in vivo. These findings have implications in the prevention and intervention of prostate cancer in man. PMID- 4026852 TI - Calcitonin inhibits the phosphorylation of various proteins in rat brain synaptic membranes. AB - The present report examines the effect of different calcitonins and analogs on the in vitro phosphorylation of brain synaptic membrane proteins. The findings demonstrate that calcitonin is a potent inhibitor of several brain synaptic proteins and that salmon and eel calcitonins are considerably more potent than thyrocalcitonin in eliciting this effect. Deletion of leucine from position 16 in salmon calcitonin sequence resulted in a drastic loss of inhibitory activity, indicating the importance for a hydrophobic residue at position 16 in the intact calcitonin molecule. The mechanism of calcitonin inhibition of protein phosphorylation was likely due to the blockade of stimulation of protein kinases by calmodulin. PMID- 4026853 TI - Neuromedin B-32 and B-30: two "big" neuromedin B identified in porcine brain and spinal cord. AB - In mammalian spinal cord, we have previously discovered "neuromedin B", whose structure is closely related to amphibian bombesin. By utilizing a specific radioimmunoassay for neuromedin B, we have isolated two novel "big" neuromedin B, designated neuromedin B-32 and B-30, from pig brain and spinal cord, both of which were identified as N-terminally extended forms of neuromedin B. The amino acid sequence of neuromedin B-32 was determined to be: Ala-Pro-Leu-Ser-Trp-Asp Leu-Pro-Glu-Pro- Arg-Ser-Arg-Ala-Gly-Lys-Ile-Arg-Val-His-Pro-Arg-Gly-Asn-Leu-Trp Ala- Thr-Gly-His-Phe-Met-NH2, while neuromedin B-30 was found to be an N-terminal two amino acids deleted form of neuromedin B-32. Isolation of a family comprising neuromedin B, B-30 and B-32 is indicative of their biosynthetic relationship. PMID- 4026854 TI - Evidence for peroxisomal hydroxylase activity in rat liver. AB - This study presents evidence for the first time that rat liver peroxisomes contain a hydroxylase capable of converting 3 alpha, 7 alpha, 12 alpha,- trihydroxy-5 beta-cholestane to a cholestanetetrol. Furthermore, this hydroxylase differs from both the mitochondrial and microsomal enzymes in its response to various co-factors. Highly purified peroxisomal, mitochondrial, and microsomal fractions from cholestryamine-treated rats were incubated with [22(23)-3H]3 alpha,7 alpha,12 alpha,-trihydroxy-5 beta-cholestane under a variety of conditions. The products were acidified, extracted, and subjected to thin-layer chromatography to determine the amount of cholestanetetrol produced. The identification of the 25- and 26-hydroxylated products from the incubations with the microsomes was confirmed by gas chromatography-mass spectrometry. Peroxisomal fractions incubated with a NADPH-generating system, Mg2+, and ATP showed a rate of 40 pmol/min/mg conversion of 3 alpha,7 alpha,12 alpha,-trihydroxy-5 beta cholestane to a cholestanetetrol. Co-factor studies indicated that both the peroxisomal and mitochondrial hydroxylase activities were dependent on NADPH, Mg2+, and ATP (with different concentration requirements) whereas the microsomal hydroxylase(s) required only NADPH. An abstract of this work has been published (1). PMID- 4026855 TI - Biosynthesis of type IX collagen during chick limb development. AB - We analyzed the collagens synthesized by developing chick limbs (stages 22 to 34). Type IX collagen synthesis started at stage 26, concurrently with the chondrogenic differentiation of limb mesenchyme, and gradually increased during subsequent stages. By stage 34, the central cartilaginous region of the limbs substantially synthesized type IX collagen, in addition to cartilage-specific type II collagen, while the outer non-cartilaginous region of the limbs synthesized predominantly type I collagen. The present study indicates that type IX collagen is cartilage-specific and can be used as a marker for the chondrogenic phenotype. PMID- 4026856 TI - Dexamethasone directly inhibits snake venom phospholipase A. AB - Dexamethasone was found to directly inhibit snake venom phospholipase A2 within 3 to 10 minutes. To detect this effect, the incubation time seems to be critical. Moreover, the inhibitory effect of dexamethasone and mepacrine were additive with each other. We speculate that this direct inhibitory effect on phospholipase A2 plays a part in its strong biological activity. PMID- 4026857 TI - Comparison of water exposed area of cholera toxin when free in solution and bound to liposomes containing the ganglioside GM1. AB - Membrane impermeable diazocoupling reagents were used for studying the water exposure of subunits (alpha, beta, gamma) of cholera toxin (CT) when bound to liposomes containing the ganglioside GM1 (Lip-GM1). The interaction between CT with Lip-GM1 shielded the binding region in particular, since a maximum of one amino acid residue on each beta subunit was modifiable. When CT was labeled free in solution five residues of each beta subunit can be coupled, but it produced loss of binding ability. New area of beta subunit was exposed to reagents after having removed alpha subunit. This labeling may serve as a tool to assess the topology of CT upon binding with Lip-GM1. PMID- 4026858 TI - Sequence homology among the coat proteins of gemini viruses. AB - The coat proteins of the gemini viruses - African cassava latent virus, tomato golden mosaic virus and maize streak virus - are shown to have reasonable to good amino acid sequence homology. It is suggested that the maize streak virus genome is ancestral and the bipartite genomes of the other viruses evolved from it. PMID- 4026859 TI - The cellulolytic enzyme complex of Clostridium thermocellum is very large. AB - The cellulolytic enzyme system bound to cellulose during the early stages of growth of C. thermocellum on this substrate was resolved into two major complexes. These complexes, as viewed by electron microscopy, are spherical particles with diameters of 210 A and 610 A and calculated molecular weights of 4.2 million and 102 million daltons, respectively. PMID- 4026860 TI - An inhibitory protein of intestinal fluid secretion reverses neuronal GABA transport. AB - Intestinal challenge with cholera toxin induces the synthesis of a hormone-like protein which counteracts intestinal hypersecretion. This study shows that the protein also inhibits GABA transport across the plasma membrane of Deiters' cells in rabbits. The inhibitory action of the protein was dose dependent, and 10(3) times more potent than met 5-enkephalin, hitherto the most effective known inhibitor of GABA transport in vitro. The influence of the protein on the plasma membrane was reversible, and did not affect either postsynaptic binding or uptake of GABA. PMID- 4026861 TI - The 5-hydroxyl of myo-inositol is essential for uptake into HSDM1C1 mouse fibrosarcoma cells. AB - We attempted to replace the myo-inositol in cellular inositol phosphatides with 5 deoxy-myo-inositol to evaluate the role of inositol 1,4,5-trisphosphate as a second messenger. This analog, lacking a 5-hydroxyl, might be incorporated into 5 deoxyphosphatidylinositol and converted to the corresponding phosphatidylcyclitol 4-phosphate but could not be converted to phosphatidylinositol 4,5-diphosphate, the precursor of the second messenger molecule inositol 1,4,5-trisphosphate. We synthesized 5-deoxy-myo-inositol and found that this analog does not replace myo inositol as an essential growth factor for essential fatty acid deficient HSDM1C1 mouse fibrosarcoma cells. Furthermore, [5-3H]-5-deoxy-myo-inositol was neither incorporated into the phospholipids nor accumulated in the cytoplasm of these cells. It appears that this cell line has a specific myo-inositol uptake system that excludes a potentially harmful analog of inositol. PMID- 4026862 TI - A transition-state-analog inhibitor influences zinc-binding by Aeromonas aminopeptidase. AB - The transition-state-analog inhibitor, 1-butaneboronic acid, markedly enhances the uptake of one g-atom of Zn2+ ions from a metal ion buffer system by Zn depleted Aeromonas aminopeptidase. In contrast, a substrate-analog inhibitor, n valeramide, does not perturb the equilibrium between Zn2+ ions and the enzyme in a metal ion buffer system. These results establish a role for metal ions in the binding of 1-butaneboronic acid to Aeromonas amino-peptidase and strongly imply that a bound Zn2+ ion interacts directly with substrate during catalysis but not during initial binding of substrate. PMID- 4026863 TI - Analysis of thyroid hormone effects on myosin heavy chain gene expression in cardiac and soleus muscles using a novel dot-blot mRNA assay. AB - Effects of thyroid hormone on myosin heavy chain (MHC) gene expression were compared in ventricle and soleus muscle of hypothyroid rats, since in this condition, both muscle types express predominately beta-MHC mRNA. Changes in MHC mRNAs were analyzed using synthetic oligonucleotide probes complementary to the 3' untranslated region of the MHC mRNAs. The results indicated that daily treatment with 3,5,3'-triiodo-L-thyronine (T3) at a dose of 2 micrograms/100 g body weight increased alpha-MHC mRNA content in heart muscle by 600% and decreased beta-MHC mRNA by 70% within 48 h. In soleus muscle, beta-MHC mRNA levels were not affected by 9 wks of treatment, however, Fast IIa-MHC mRNA was increased by 150% at 7 wks and 300% after 9 wks of T3 administration. Thus, regulation of MHC gene expression by thyroid hormone is both gene and tissue specific. PMID- 4026864 TI - Sexual dimorphism in amino acid compositions of mouse prolactin. AB - Sexual dimorphism was found in amino acid compositions and immunogenecity of variant types of prolactin (PRL) purified from the pituitary gland of normal adult C57BL mice by a high performance liquid chromatography. From the pituitary gland of female mice, three female variant types of PRL were isolated, whereas from the pituitary gland of male mice, two male variant types of PRL (M1-PRL and M3-PRL) and a female variant type of PRL (M2-PRL) were obtained. The amino acid composition of M3-PRL was different from any of female variant types which were very similar to each other and contained less varine, isoleucine, leucine, tyrosine and lysine but more alanine than the latter. Immunoreactivity of any of female variant types of PRL against anti-PRL serum was 100%, whereas that of M1 PRL was as much as 85% and that of M3-PRL was nearly undetectable. PMID- 4026865 TI - Influence of myocardial isomyosins on cardiac performance and oxygen consumption. AB - There was 21% isomyosin V1 in the 12 month SHR (Spontaneous Hypertensive Rat) and 70% isomyosin V1 in the 6 month WKY (Wystar-Kyoto), nevertheless there was no difference in maximum developed pressure nor maximum dP/dt in the isovolumically beating hearts of the two sets of animals. [Hearts were perfused with hypercalcemic perfusate in the presence of isoproterenol (10(-7)M)]. There was, however, a a 32% reduction in oxygen consumption per gram of dry weight per beat in the 12 month SHR as compared to the 6 mo WKY. Associated with a shift towards isomyosins V2 and V3 in the 6 and 12 month WKY and SHR there was no corresponding change in maximum dP/dt nor developed pressure, but there was a conservation in oxygen consumption. PMID- 4026866 TI - Hydroxylation of benzoate and its chlorinated derivatives in Aspergillus niger. AB - Comparison of the properties of a purified benzoate-4-hydroxylase, using benzoic acid and its chlorinated derivatives as substrate, suggests that the same enzyme operates during the initial hydroxylation of benzoate, 2-chlorobenzoate (2-cba), and 3-chlorobenzoate (3-cba) in A.niger. PMID- 4026867 TI - Affinity chromatography of human serum proteins using immobilized lectin from Allomyrina dichotoma. AB - The beta-D-galactoside-specific lectin from Allomyrina dichotoma reacts with serum proteins which contain the corresponding carbohydrate moieties. By affinity chromatography of human serum using the insolubilized lectin coupled to Sepharose, it is possible to fractionate human serum proteins in 2 groups: those which react with the lectin (alpha 1-acid glycoprotein, haptoglobin, etc.) and those which do not (albumin, Gc-globulin, etc.). IgG is the only serum protein that can be found in both groups. PMID- 4026868 TI - Human uropepsinogen is a new human pepsinogen proisozyme. AB - The first 20 amino acid residues of human uropepsinogen has been determined to be H2N-Ile-Met-Tyr-Lys-Val-Pro-Leu-Pro-Ile-Lys-Lys-Ile-Leu-Val Val-Pro-Leu-Ile-Val Tyr-Met. Comparison with the sequence of human stomach pepsinogen shows that these proteins are isozymes. Comparative sequence data are presented and discussed. PMID- 4026869 TI - Structure of a novel diphosphonoglycosphingolipid isolated from the skin of Aplysia kurodai. AB - A new phosphonoglycosphingolipid containing two 2-aminoethylphosphonate residues was isolated from the skin of Aplysia kurodai, a marine gastropod, using two systems of silicic acid chromatography. By methanolysis, permethylation, mild acid hydrolysis and hydrogen fluoride treatment combined with thin layer chromatography and gas chromatography-mass spectrometry, the new phosphonoglycosphingolipid was shown to be 3-O-MeGal (1----3) GalNAc (1----3) [6' O-(2-aminoethylphosphonyl) Gal (1----2)] [2-aminoethylphosphonyl (----6)] Gal (1- --4) Glc (1----1) ceramide. Most of the fatty acid (90 per cent) was palmitic acid. Octadeca-4-sphingenine and anteiso-nonadeca-4-sphingenine were the major sphingosine bases of the new glycolipid. PMID- 4026870 TI - ATP-dependent stabilization against microsomal factor-induced loss of unoccupied glucocorticoid receptors. AB - ATP stabilizes the unoccupied glucocorticoid receptor from brain at 12 degrees C, but only in the presence of a destabilizing microsomal factor. This stabilization is optimal at an ATP concentration of about 1 mM, higher concentrations resulting in an increase in the rate of heat inactivation. Other nucleotides, including CTP, GTP, UTP, ADP, cAMP and cGMP were ineffective in stabilizing receptors, although additions of some of these nucleotides actually resulted in further destabilization of the unoccupied glucocorticoid receptor. PMID- 4026871 TI - The conversion of L-cystathionine into the cyclic ketimine form by heated rat liver extracts containing cystathionase and transaminase activities. AB - Rat liver homogenates heated for 10 min at 60 degrees C incubated with L cystathionine yield cystathionine ketimine which was identified by its typical UV spectrum and by cochromatography with authentic samples on the amino acid analyzer. Alanine and alpha-amino butyric acid have been also detected among the final products. The reaction is due to heat stable gamma-cystathionase and transaminases present in the extracts. Cystathionase produces alpha-keto butyric acid and pyruvic acid which are then used for the transamination of the remaining cystathionine to yield the ketimine. This is the first report indicating the occurrence in a mammalian tissue of an enzymatic system using cystathionine for reactions differing from the traditional transulfuration to cysteine. PMID- 4026872 TI - Selenium-dependent and non-selenium-dependent glutathione peroxidase in human tissues of New Zealand residents. AB - Glutathione peroxidase was assayed in human tissues of New Zealand residents by the coupled assay method. Total glutathione peroxidase was assayed using cumene hydroperoxide. The non-selenium-dependent activity was not detected with t-butyl hydroperoxide and thus was determined from the difference between total activity and the selenium-dependent activity using hydrogen peroxide or t-butyl hydroperoxide. Only selenium-dependent activity was found in whole blood, erythrocytes, platelets and biopsy skeletal muscle. A small non-selenium dependent activity was measured in plasma and a larger activity in biopsy liver supernatant and homogenate. Glutathione-S-transferase was detected in all tissues. PMID- 4026873 TI - Comparison of populations of mRNA coding fumarase in rat brain and liver. AB - The populations of mRNA encoding mitochondrial and cytosolic fumarases in the poly A+ RNA fractions purified from polysomes of rat brain and liver were examined. When the in vitro translation products programmed by the poly A+ RNA fraction obtained from rat brain were purified by immunoprecipitation with anti fumarase antibody and analyzed by SDS polyacrylamide gel electrophoresis and fluorography, only one polypeptide of 50 KD was detected as a precursor of fumarase. In contrast, by the same method, two polypeptides of 50 KD and 45 KD, which is the same size as mature fumarase, were detected as precursors of rat liver fumarase. These results suggest that rat brain polysomes contain only one population of mRNA coding a 50 KD precursor of mitochondrial fumarase with little or no mRNA of the cytosolic fumarase, whereas rat liver polysomes contain two types of mRNA for mitochondrial and cytosolic fumarases, respectively. These findings are consistent with the fact that the brain is the only organ in rats known not to contain cytosolic fumarase. PMID- 4026874 TI - Effects of anesthetics and dichlorodifluoromethane on the activities of glyceraldehyde-phosphate dehydrogenase and pectin methylesterase. AB - Solutions of glucose-3-phosphate dehydrogenase (GPD) and pectin methylesterase (PME) were exposed to various anesthetics and dichlorodifluoromethane (F-12) to determine the abilities of these chemicals to inhibit enzyme activity. An aqueous solution of PME was exposed to saturation levels of the test chemicals for 30 min at 21 degrees. All test chemicals were inhibitory (measured after release of the test chemical) with propane being most inhibitory followed in order by F-12, cyclopropane, Ethrane (F2HCOF2CCHClF) and halothane (CF3CHClBr). GPD was exposed to various concentrations of F-12 and halothane for various times at 0 degrees and 33 degrees. Halothane at 33 degrees and a saturation concentration reduced the initial reaction velocity of GPD to zero after a 10-min exposure period. F-12 was somewhat less inhibitory than halothane, but inhibition in all instances was irreversible. Halothane was found to affect the circular dichroism and optical rotary dispersion spectra of GPD, with the magnitude of the changes generally increasing with treatment time. The observed changes were believed to arise from side-chain transitions of GPD. PMID- 4026875 TI - Lack of effect of added liposomes on veratridine activation of 22Na+ uptake in rat brain synaptosomes. AB - Partially purified egg yolk phospholipids in the form of both small and large unilamellar liposomes at lipid concentrations of 30 mg/ml and higher inhibited veratridine activation of sodium channel specific 22Na+ uptake by rat brain synaptosomes. Chromatographically purified egg yolk phosphatidyl choline liposomes did not show this inhibition even at lipid concentrations up to 125 mg/ml. This demonstrates that the inhibition of veratridine-activated 22Na+ uptake was due to an impurity in the lipid rather than an ability of the liposomes to absorb and immobilize the lipophilic veratridine molecule. PMID- 4026876 TI - 2-Acetamido-p-benzoquinone: a reactive arylating metabolite of 3' hydroxyacetanilide. AB - The covalent binding to protein of 3'-hydroxyacetanilide (3HAA), its primary metabolite 2',5'-dihydroxyacetanilide (2,5DHAA), and a putative secondary metabolite thereof, 2-acetamido-p-benzoquinone (APBQ), was studied in hepatic microsomal preparations from phenobarbital-pretreated mice. All compounds were found to bind irreversibly to microsomal protein, APBQ being by far the most effective member of the group. In the case of 3HAA, binding was dependent upon the presence in incubation media of the co-factor NADPH, indicating that metabolism of 3HAA was necessary for the generation of a reactive intermediate. In contrast, NADPH decreased by more than 2-fold the binding of both 2,5DHAA and APBQ. The free radical spin-trapping agent alpha-(4-pyridyl-1-oxide)-N-tert butylnitrone (POBN) did not reduce the binding of 3HAA to protein. These results support the contention that metabolic activation of 3HAA is a two-step process which involves initial aromatic hydroxylation to give the substituted hydroquinone, 2,5DHAA, followed by a second oxidation reaction (which may not be enzyme-mediated) to produce the benzoquinone derivative, APBQ. This quinone is a reactive, electrophilic intermediate which may either undergo reduction back to 2,5DHAA or bind covalently to cellular macromolecules. PMID- 4026877 TI - The characterization of [3H]sulpiride binding sites in pig striatal membranes. AB - Pig striatal membranes have [3H]sulpiride-binding sites similar to those identified in rat striatal membranes. The pharmacological profile indicates that this binding is to dopamine receptors. Agonist displacement of [3H]sulpiride binding in pig striatal membranes is subject to guanine nucleotide regulation. This effect is mimicked by heat treatment. N-ethyl maleamide (20 microM) and dithioerythritol (3 mM) decrease agonist affinity for the [3H]sulpiride-binding site in pig striatal membranes without significantly affecting maximal displacement. PMID- 4026878 TI - Interconversions of haloperidol and reduced haloperidol in guinea pig and rat liver microsomes. AB - An alcohol metabolite of haloperidol, reduced haloperidol, is present in the tissues of haloperidol-treated patients. We have studied whether rat and guinea pig liver microsomes have the capability to reduce haloperidol and thus serve as models for human haloperidol metabolism. Interestingly, the rat microsomes did not reduce haloperidol, but possessed an NADPH-dependent, carbon monoxide inhibited mechanism to oxidize the reduced haloperidol back to haloperidol. Guinea pig microsomes efficiently reduced haloperidol molecules in a fashion not dependent on nicotinamide cofactors and not inhibited by carbon monoxide. Both of these activities were confined to the microsomal fraction. In guinea pigs, reduction of haloperidol was observed also in kidney slices, whereas brain slices proved inactive. Reduced haloperidol was also oxidized to haloperidol to a small extent in guinea pig microsomes. These in vitro experiments confirm our findings in vivo, which showed that in rats haloperidol is not reduced, while guinea pigs have a very active mechanism for reducing haloperidol. Thus, guinea pigs constitute a model for human haloperidol metabolism, and they should be used for further characterization of the reductive drug-metabolizing system. PMID- 4026879 TI - Analysis of metabolites of 2-acetylaminofluorene generated in an embryo culture system. Relationship of biotransformation to teratogenicity in vitro. AB - 2-Acetylaminofluorene (AAF) produced abnormal, open neural tubes in cultured whole rat embryos only in the presence of an added, NADPH-dependent monooxygenase system. Reactive intermediary metabolites, including N-hydroxy-AAF, N-hydroxy-2 aminofluorene, 2-nitrosofluorene and N-acetoxy-AAF, each elicited embryonic malformations under culture conditions, but a statistically significant increase in the incidence of abnormal neurulation was not observed. Using [14C]AAF and high pressure liquid chromatography (HPLC) separation techniques, the biotransformation of AAF was studied under conditions in which embryos and the monooxygenase system were coincubated. The major metabolites produced cochromatographed with 5-hydroxy-AAF, 7-hydroxy-AAF, 9-hydroxy-AAF and 3-hydroxy AAF. Other metabolic products also were detected. The embryonic effects of these major AAF metabolites were tested singly and in combination in the embryo culture system. Addition of 7-hydroxy-AAF to the embryo culture system resulted in open neural tubes in the absence of an added monooxygenase system. Other individual ring-hydroxylated metabolites produced retarded growth, but neurulation appeared normal. Ring-hydroxylated metabolites, added to the embryo culture system in combination in the same proportions as were formed during biotransformation in culture, also produced a marked increase in incidence of neural tube defects in the absence of an exogenous (added) biotransforming system. In combination with 3 , 5- and 9-hydroxy-AAF, 7-hydroxy-AAF exposure (86 microM) resulted in a 47% incidence of abnormal, open neural tubes. When tested individually, higher concentrations of 7-hydroxy-AAF (104 microM) produced a lower percentage of malformed embryos (13%). The results suggested that 7-hydroxy-AAF was principally responsible for the neural tube defects caused by AAF following monooxygenase dependent bioactivation, but that other metabolites also appeared to contribute to the observed effect. PMID- 4026880 TI - Comparison of the hepatic mixed function oxidase system of young, adult, and old non-human primates (Macaca nemestrina). AB - The influence of age on the mixed function oxidase system from a non-human primate was studied. Microsomes were isolated from the livers of female Macaca nemestrina ranging from 2 to 21 years of age. No significant age-related change was observed in either the cytochrome P-450 content or the NADPH cytochrome c reductase activity. In addition, the ability of the microsomes to metabolize benzo [a]pyrene did not change significantly with age. These observations contradict studies with liver tissue from laboratory rodents in which an age related decline in the mixed function oxidase system is generally observed. The lipid composition of the liver microsomes was studied also. Both the cholesterol and total phospholipid content of the liver microsomes increased significantly with age; however, the ratio of cholesterol to phospholipid remained constant. The percentage of individual phospholipids in the microsomes changed only slightly with age. These results provide new information on the effect of age on the mixed function oxidase system and indicate that one must be cautious in extrapolating from studies with liver tissue from laboratory rodents to primates. PMID- 4026881 TI - Maintenance of cytochrome P-450 in cultured adult human hepatocytes. PMID- 4026882 TI - Evidence that (+)[3H]amphetamine binds to acceptor sites which are not MAO-A. PMID- 4026883 TI - Synthesis of 3-phenoxybenzoic acid-containing lipids via the monoacylglycerol pathway. PMID- 4026884 TI - Suppression of rheumatoid factor synthesis by antiidiotypic antibody in rheumatoid arthritis patients with cross-reactive idiotypes. AB - The effect of antiidiotypic antibody on the in vitro production of rheumatoid factor was studied in rheumatoid arthritis patients with cross-reactive idiotypic determinants. Antiidiotypic antibodies (ascites IgG) were developed against monoclonal rheumatoid factor (Ka m-RF) by a cell fusion procedure. These antibodies were idiotype-specific, since: 1) they reacted only with F(ab')2 fragment of Ka m-RF; 2) they failed to react with normal IgM without rheumatoid factor activity; and 3) their F(ab')2 fragment inhibited the rheumatoid factor activity of Ka m-RF. The antiidiotypic antibody strongly suppressed the in vitro production of rheumatoid factor by lymphocytes from unrelated rheumatoid arthritis patients with cross-reactive idiotypes. The suppression was specific, since ascites IgG failed to suppress in vitro anti-keyhole limpet hemocyanin antibody production by the lymphocytes. These results indicate that antiidiotypic antibody may influence the regulation of rheumatoid factor production in patients with rheumatoid arthritis. PMID- 4026885 TI - The effect of D-penicillamine on pulmonary findings in systemic sclerosis. AB - D-penicillamine has been used for the treatment of systemic sclerosis for 2 decades. Forty-four systemic sclerosis patients who received a mean dose of 636 mg of D-penicillamine for 2.3 years and 48 untreated patients, who had repeat pulmonary function tests performed after a mean of 3.5 and 4.8 years, respectively, were evaluated. There were no significant changes in the vital capacity or the forced expiratory volumes during this time in either group. However, the diffusing capacity for carbon monoxide improved from 76% of predicted to 87% of predicted in D-penicillamine-treated patients. Untreated patients changed slightly, from 73% of predicted to 76% of predicted. When multiple logistic regression analysis was used to account for factors which could have biased treatment comparisons, the improvement related to use of the D penicillamine was significant (P less than 0.05). This improvement in the D penicillamine-treated patients was associated with no further progression of dyspnea or fibrosis on chest radiograph, as well as reduced skin thickening. These data suggest that D-penicillamine may be useful in the treatment of systemic sclerosis that involves the lung; however, further studies are needed. PMID- 4026886 TI - The value of complement and immune complex determinations in monitoring disease activity in patients with systemic lupus erythematosus. AB - Serial serum samples from 33 patients with systemic lupus erythematosus were tested for CH50, C3, C4, and circulating immune complexes. Circulating immune complexes were determined by 5 different assays. Disease activity was determined by a scoring system we devised. On an interpatient analysis, overall disease activity correlated significantly with levels of CH50, C3, and a positive result on C1q binding assay. However, with the exception of depressed C3 levels, the sensitivity, specificity, and predictive values of all the serologic tests were low. An intrapatient analysis revealed a patient-specific activity parameter in 11 of the 33 patients. We conclude that these serologic tests are not reliable in assessing disease activity in patients with systemic lupus erythematosus, although a small subgroup of patients will exhibit a patient-specific activity parameter. PMID- 4026887 TI - In vitro production and scavenging of hydrogen peroxide by D-penicillamine. Relationship to copper availability. AB - The capacity of D-penicillamine (DP) to produce or scavenge hydrogen peroxide was investigated. DP added to copper produced H2O2. Greater production was observed with copper sulfate than with copper bound to ceruloplasmin. In contrast, DP in the absence of copper scavenged H2O2, as measured in a direct assay. Furthermore, DP or D-cysteine alone reversed H2O2-mediated inhibition of concanavalin A stimulated mononuclear cell proliferation. These opposing immunomodulating properties of DP may be relevant to its toxic or therapeutic actions in rheumatoid arthritis. PMID- 4026888 TI - Salicylate-induced depletion of endogenous inorganic sulfate. Potential role in the suppression of sulfated glycosaminoglycan synthesis in murine articular cartilage. AB - Sodium salicylate has been shown to suppress glycosaminoglycan (GAG) synthesis by articular hyaline cartilage in vitro. We investigated the in vivo effect of sodium salicylate on murine patellar cartilage, using incorporation of intraperitoneally administered 35S-sulfate as a measure of sulfated GAG synthesis. Our results indicated that a single dose of sodium salicylate (200 mg/kg) inhibited in vivo sulfated GAG synthesis by 56%, compared with controls, and had no effect on sulfated GAG breakdown. A striking finding was that sodium sulfate treatment reduced the serum concentration of inorganic sulfate from 1.1 mM to approximately 0.3 mM, and that this serum reduction was associated with a twofold increase in urinary excretion of sulfate. Using anatomically intact patellar cartilage, in vitro studies clearly showed that, in concentrations reached in vivo (greater than or equal to 1 mM), salicylate suppressed murine chondrocyte GAG synthesis. However, in the presence of serum, the effects of 1 mM salicylate were abolished. We also found that sulfated GAG synthesis was clearly inhibited at low concentrations of sulfate (less than 0.5 mM). Our data indicate that sodium salicylate can suppress articular chondrocyte sulfated GAG synthesis in vivo, and that this effect may particularly be due to a drug-induced reduction of endogenous sulfate. PMID- 4026889 TI - Computed tomography in the diagnosis of early ankylosing spondylitis. AB - Computed tomography (CT) was compared with plain radiography and quantitative sacroiliac (SI) scintigraphy in 28 patients with early ankylosing spondylitis (AS) of less than or equal to 10 years duration. Compared with conventional radiography, CT improved delineation of the SI joints and revealed more abnormalities and higher grades of sacroiliitis; this was significant in patients with early AS of less than or equal to 3 years duration. Quantitative sacroiliac scintigraphy showed higher SI joint: sacrum ratios of radioisotope uptake in patients with AS compared with controls. However, its diagnostic usefulness was limited by the frequency of inconsistent results and the lack of specificity. CT examination of the SI joints may be a useful adjunct in the diagnosis of early AS. PMID- 4026890 TI - Sympathetic synovial effusions associated with septic arthritis and bursitis. PMID- 4026891 TI - Eosinophilic fasciitis in a two-year-old child. PMID- 4026892 TI - Severe reflex neurovascular dystrophy in childhood. PMID- 4026893 TI - Adult-onset Still's disease: a case with onset during pregnancy. PMID- 4026894 TI - Apophyseal joint ankylosis of the cervical spine in adult-onset rheumatoid arthritis. PMID- 4026895 TI - Erosive granulomatous arthritis in Crohn's disease. PMID- 4026896 TI - Joint involvement in psoriasis: uncommon or frequent? PMID- 4026897 TI - Preliminary study of testosterone levels in rats with adjuvant arthritis. PMID- 4026898 TI - Limitations of dose tolerance studies on predictability for phase III. AB - Phases I, II and III of the development of a new drug are briefly described. The limitations of dose tolerance studies in Phase I are considered in relation to their predictive value for Phase III. Limitations on predictability may arise because of differences between Phase I and Phase III in both study population and study design. The study population in Phase I, in contrast with Phase III, is usually numerically small, male, young, of average size, healthy, asymptomatic and free from other medication. The Phase III population may be of different nationality or race. Phase I studies are always of short duration. Drug administration is usually in the morning and may be accompanied by more restrictions on diet, smoking and alcohol intake than in Phase III trials. The implications of these differences in study population and design are discussed. The predictive value of dose tolerance studies for Phase III can be substantial, provided that the results are interpreted sensibly. However, the tolerance studies should perhaps be regarded mainly as an essential preliminary to single and multiple dose kinetic, dynamic and interaction studies; the combined experience of these trials should have much greater predictive power for Phase III than dose tolerance studies alone. PMID- 4026899 TI - Synthesis and antimicrobial activity of some benzofuran derivatives. AB - The Friedel-Craft's acylation of 2,3-diphenyl-5-methylbenzofuran 1a with succinic anhydride gives beta-(2,3-diphenyl-5-methylbenzofuranoyl)propionic acid 1b. Acid 1b reacts with hydrazines yielding the corresponding tetrahydropyridazinones 2. 4,5-Dihydro-1,2-oxazin-6H-6-one 6 is formed by reaction of 1b with hydroxylamine hydrochloride. The reaction of the pyridazinone 2a with dialkyl sulfates, ethyl chloroacetate, Grignard reagents, amines in presence of formaldehyde (Mannich reaction), o-amino-phenol and thiourea has been investigated. The antimicrobial activities of compounds 1a-c, 2a-c, e, f, 4a, b and 5a, b as well as 7b are studied. PMID- 4026900 TI - Effect of piracetam on cerebral blood flow and somatosensory evoked potential during normotension and hypotensive ischemia in cats. AB - The effect of piracetam (Nootrop), 200 mg/kg body weight, on cerebral blood flow (CBF) and somatosensory evoked potential (EP) was studied in a control group (9 cats, mean arterial blood pressure (MABP) = 113.1 +/- 12,63 mmHg, CBF = 71.0 +/- 24.16 ml/100 g/min) and in another group of 11 cats, in which CBF was reduced to 52.2 +/- 20.17 ml/100 g/min by hemorrhagic hypotension (MABP = 55.9 +/- 18.95 mmHg). Piracetam did not affect CBF significantly in the normotensive group, but decreased the EP slightly. The decrease of the surface negative (N1) wave of the EP reached a significant level 10 min (9.9 +/- 12.05%) and 30 min (15.6 +/- 13.05%) after piracetam. In contrast, CBF and EP were increased by piracetam in the hypotensive group: CBF was significantly improved 10 min (32.0 +/- 64.74%) and 30 min (28.8 +/- 45.11%), and N1 10 min (23.0 +/- 26.47%) after piracetam, while the enhancement of the surface positive wave (P1) of the EP reached a significant level during the entire observation period of 90 min. The results indicate a beneficial action of piracetam on brain tissue whose function is impaired by deficient blood supply. PMID- 4026901 TI - Cimetropium: characterization of antimuscarinic and spasmolytic properties. AB - Cimetropium displaced 3H-NMS binding from membranes derived from gastrointestinal smooth muscle. The affinity of cimetropium for intestinal muscarinic receptors was in the range 70-100 nM. The competitive antagonism of cimetropium was demonstrated in guinea-pig ileum and taenia coli stimulated by bethanechol. Comparing pA2 values, cimetropium (8.19 and 7.91, resp.) was 0.3 times as potent as atropine (8.52 and 8.41, resp.). Cimetropium displayed strong inhibitory effects towards BaCl2 and 5-hydroxytryptamine induced contractions of the guinea pig ileum. The compound was devoid of antihistaminic or Ca++ channel blocking activity. A binding study performed in vivo confirmed the ability of i.v. cimetropium to displace 3H-N-methylscopolamine binding from muscarinic receptors in peripheral organs. In addition, when injected into ileal loops, cimetropium displaced 3H-NMS binding solely from the surrounding tissue of the loop, indicating a topical effect of the compound. PMID- 4026902 TI - The lack of hepatotoxicity in the rat with the new and reversible MAO-A inhibitor moclobemide in contrast to iproniazid. AB - In phenobarbital-pretreated rats iproniazid produces distinct hepatotoxic symptoms, whereas moclobemide (Ro 11-1163) does not. Iproniazid's hepatotoxic effect is most impressive in histopathology where marked liver necrosis can be seen. Differences between the two compounds are also noted in the body weight development, mortalities and some haematological and blood chemistry parameters. The reversible and specific monoamine oxidase (MAO)-A inhibitor moclobemide, a benzamide, is therefore completely different from the classical irreversible MAO inhibitors of the hydrazine type and, as also confirmed in the clinical studies, does not have any hepatotoxic effect. PMID- 4026903 TI - Polysorbate 80: a pharmacological study. AB - Polyoxyethylene (20) sorbitan monooleate (polysorbate 80, Tween 80), a surfactant, has been widely used as a solvent for pharmacological experiments. In the present study, polysorbate 80 was found to have toxicity of a low order in both the mice and rats when given by i.p. and p.o. routes. It produced mild to moderate depression of the central nervous system with a marked reduction in locomotor activity and rectal temperature, exhibited ataxia and paralytic activity and potentiated the pentobarbital sleeping time. On intravenous administration in dogs, it had a dose-dependent hypotensive effect. Polysorbate 80 did not have a direct stimulant or relaxant effect on either guinea pig ileum or rat uterus, however, it antagonised the contractions induced by acetylcholine, histamine, barium, 5-hydroxytryptamine and carbachol in a dose-dependent manner. A direct relaxant effect was observed on rabbit jejunum. A dose-dependent myocardial depressant effect was observed on guinea pig and rabbit paired atrial preparations. On the electrically-driven guinea pig left atrial preparation, polysorbate 80 exhibited a dose-dependent negative inotropic action. Polysorbate 80 did not induce diuresis in rats upto a dose of 2.5 ml/kg. The results of the present study indicate that polysorbate 80 can neither be used as a solvent for isolated tissue experiments nor when considered for intravenous administration. However, polysorbate 80 can be employed safely as a vehicle for neuropsychopharmacological experiments in doses not exceeding 1 ml/kg. PMID- 4026904 TI - Pharmacokinetics and metabolism of ryodipine in rats. AB - 2,6-Dimethyl-3,5-dimethoxycarbonyl-4-(o-difluoromethoxyphenyl)-1, 4 dihydropyridine (ryodipine, PP-1466) at oral administration in the form of a suspension with Tween (polysorbate) 80 addition is comparatively rapidly absorbed in the gastro-intestinal tract and circulates in blood for a long period of time. PP-1466 practically does not bind to plasma proteins. The drug is mainly excreted via the kidneys and with faeces by 49 and 46% of the dose administered after 96 h, respectively. PP-1466 metabolites are present in rat urine-2,6-dimethyl-4 arylpyridine-3,5-dicarbonic acid derivatives: oxidation product of PP-1466 dihydropyridine cycle into pyridine one, products of partial or complete hydrolysis of ester groups of PP-1466 oxidized form, lactones. There have been performed the synthesis of labelled 14C-PP-1466 as well as counter-synthesis of PP-1466 metabolites. Unchanged PP-1466 is not detected in urine. PMID- 4026905 TI - Absorption, distribution, metabolism and excretion of 2,6-dimethyl-3,5 dimethoxycarbonyl-4-(o-difluoromethoxyphenyl)- 1,4-dihydropyridine (PP-1466) in rats. AB - In this experiment, the absorption, excretion, distribution and metabolism of 2,6 dimethyl-3,5-dimethoxycarbonyl-4-(o-difluoromethoxyphenyl)-1, 4-dihydropyridine (PP-1466) were investigated following oral or intravenous administration, single dose or repeated dose administration using male SLC-Wistar rats and the results of this investigation were summarized as follows: After oral administration of 14C-PP-1466 to rats, the blood level reached the maximum at 1 h and decreased with the biological half-life of about 5 h. The unchanged drug concentration in plasma was 30% of total concentration in plasma and disappeared at 6 h. The high radioactivities in the liver, kidney, fat, lung and adrenal gland were observed after oral and intravenous administration. After oral and intravenous administrations, the excretion in feces and urine during 48 h was 63.0 and 32.4, 58.6 and 41.6%, respectively. Biliary excretion amounted to 57.6 and 46.2% during 48 h, respectively. Six metabolites were found in the urine of rats. Three of them were identified as 2,6-dimethyl-3-carbomethoxy-4-(2-difluoromethoxyphenyl)-5 carboxylic acid pyridine, 2-methyl-3-carbomethoxy-4-(2-difluoromethoxyphenyl)-5 carboxylic acid-6-hydroxymethyl pyridine and its lactonizing analogue. These three metabolites covered 54% of total urinary metabolites. After oral repeated administration for three weeks, the excretion ratio of radioactivity in urine and feces was constant during the administration and no accumulation was observed in rat tissues. PMID- 4026906 TI - Effects of 7-ethoxycarbonyl-4-hydroxymethyl-6,8-dimethyl-1(2H)-phthalazinone (EG 626), a new phosphodiesterase inhibitor, on the cardiovascular system of the dog. AB - 7-Ethoxycarbonyl-4-hydroxymethyl-6,8-dimethyl-1(2H)-phthalazinone (EG 626) (0.3-3 mg/kg i.v.), a new cyclic AMP phosphodiesterase inhibitor, increased femoral, renal, coronary, carotid, vertebral and sagittal blood flows in anesthetized dogs. Systolic tension in left ventricular wall, heart rate and cardiac output also increased. These properties of EG 626 resembled those of papaverine (0.1-1 mg/kg i.v.). However, the heart rate increasing activity of EG 626 was less than that of papaverine at equipotent does on the vasodilator actions. In the isolated right atria of guinea pigs, EG 626 was more selective for increasing contractility than for increasing the sinus rate. The cardiovascular actions of EG 626 were also examined in perfused vascular beds and papillary muscle preparations of dogs. An i.v. infusion of EG 626 or papaverine (0.3 mg/kg/min) enhanced the increasing action of isoprenaline on left ventricular systolic pressure and coronary sinus outflow. The vasodilator effect of EG 626 was no suppressed by atropine, propranolol nor clemastine, and the inotropic action was not modified by pindolol. These results indicate that EG 626 may be a useful vasodilator with a cardiotonic activity but with less potency to cause tachycardia than papaverine. PMID- 4026907 TI - Relationship between positive inotropic action and blood levels of denopamine in cats. AB - The relationship between the positive inotropic action and blood levels of (-) (R)-1-(p-hydroxyphenyl)-2-[(3,4-dimethoxyphenethyl)amino]ethanol (denopamine, TA 064) was studied after intraduodenal administration of 3H-denopamine (100 micrograms/kg) in cats. The increase in cardiac contractile force attained the peak (about 100% increase) 15 min after the administration and the effect persisted for over 90 min. The blood levels of denopamine also reached the peak at 15 min with a concentration of 20 ng/ml and decreased gradually thereafter. Thus, it was indicated that the time courses of the increase in cardiac contractile force were closely related to those of blood levels of the drug. Furthermore, denopamine was distributed to the liver, kidney, parotid gland and heart, followed by being excreted into the urine and bile mostly as metabolites. PMID- 4026908 TI - Variability in the pharmacokinetics of atenolol and metoprolol. AB - 18 healthy volunteers received conventional atenolol (Tenormin) 50 mg once daily and metoprolol 50 mg twice daily for 6 days in a balanced randomised cross-over fashion. There was a wash-out period of two weeks between each phase. Plasma concentrations of the drugs were measured on the last day of each phase. Comparison of the coefficients of variation showed a lower variability in the pharmacokinetics of atenolol compared to metoprolol. The clinical implications of these findings are discussed. PMID- 4026909 TI - Correlation between digoxin plasma levels and arterial blood pH. AB - The correlation between arterial blood pH and digoxin plasma levels was studied after digoxin (Eudigox) administration a) in a single p.o. dose, b) in a steady state p.o. regimen, or c) i.v. The clinical trial was carried out on 26 male hospitalized patients selected and divided into groups according to their arterial blood pH values, which ranged between 7.20 and 7.53. Arterial blood pH proved to be directly correlated with digoxin plasma levels and with the corresponding AUC and inversely with the total plasma clearance of the drug. The data may explain the strongly reduced activity shown by digoxin in patients suffering from respiratory acidosis in clinical practice. PMID- 4026910 TI - Dysgeusia after high dose dipyridamole treatment (short communication). AB - Chemosensory disorders as a side effect of dipyridamole treatment have not been previously described. A case of dysgeusia during treatment with dipyridamole for congestive heart failure is reported. PMID- 4026911 TI - [The effect of infusion rate on pharmacokinetic parameters of azlocillin and mezlocillin]. AB - Azlocillin (Securopen) and mezlocillin (Baypen) were given to 3 healthy subjects as intravenous infusion. The dose of 4 g was administered to each person within 5, 15, and 30 min in a randomized crossover design. Using HPLC the unchanged penicillin antibiotics were determined quantitatively, their metabolites were assessed qualitatively. The same specimens were also studied by means of a bioassay (agar diffusion technique). Both methods yielded similar serum and urine concentrations besides the urinary excretion of azlocillin. Here the bioassay measured higher amounts indicating an antibacterially active metabolite being excreted in the urine. No dependence upon infusion time was found. Since both drugs were tested with the same dosis in the same subjects, their pharmacokinetic parameters could be compared: mezlocillin, being more lipophilic than azlocillin, showed a higher volume of distribution and therefore lower serum concentrations. Renal clearance was the same for both drugs, but mezlocillin was excreted to a smaller extent in the urine. Higher total clearance and shorter elimination half life of mezlocillin indicate a greater extrarenal elimination. The results suggest fast application of both penicillins. There is no pharmacokinetic reason for a prolongation of infusion times. PMID- 4026912 TI - Single dose pharmacokinetics of tiaprofenic acid. Effects of food and severe renal insufficiency. AB - The single oral dose pharmacokinetics of tiaprofenic acid (Surgam) has been investigated in fasting and non-fasting healthy volunteers (200 and 300 mg) and in fasting patients with severe renal insufficiency (200 mg). A dose independent pharmacokinetics of tiaprofenic acid was shown in fasting healthy volunteers and the following parameters were calculated after administration of 200 mg: tl = 0.53 +/- 0.15 h, tm = 1.28 +/- 0.19 h, cm = 27.1 micrograms/ml, ka = 2.79 +/- 0.93 h-1, lambda 2 = 1.06 +/- 0.14 h-1, t1/2 = 3.0 +/- 0.2 h, AUCl-infinity = 80 +/- 7 mg X h/l, Clt = 43.8 +/- 3.7 ml/min and V beta = 11.1 +/- 0.8 l. A small, but significant positive deviation from linearity was observed with increasing dose for cm and AUCl-infinity in non-fasting healthy volunteers, probably due to a slightly higher bioavailability of the 300 mg formulation in the non-fasting state as compared with the 200 mg formulation. Intake of food decreased cm significantly at both dosage levels from 27.1 to 19.1 micrograms/ml and from 47.9 to 39.1 micrograms/ml for 200 and 300 mg, respectively. The absorption kinetics of tiaprofenic acid was not significantly different in fasting healthy volunteers and in fasting patients with severe renal insufficiency. However, a significant increase in t1/2 and AUCl-infinity to 5.8 +/- 0.9 h and 173 +/- 34 mg X h/l, respectively, and a significant decrease in total body clearance to 25.5 +/- 5.3 ml/min were observed in this category of patients. No correlation was found between creatinine clearance and tiaprofenic acid clearance. PMID- 4026913 TI - Steady state pharmacokinetics of tiaprofenic acid in elderly patients. AB - Tiaprofenic acid (Surgam) steady state pharmacokinetics was investigated in eight elderly patients with three different dosage regimens: 200 mg twice daily, 400 mg twice daily and 200 mg three times daily. The following dose independent pharmacokinetic parameters were evaluated from a two-compartment open model; absorption lag time: 0.23 +/- 0.08 h, absorption rate constant: 4.32 +/- 0.51 h 1, distribution rate constant: 1.31 +/- 0.13 h-1 and elimination half-life: 4.66 +/- 0.42. An increase in dose produced a significant and proportional increase in tiaprofenic acid peak and trough serum concentrations at steady state. In contrast to the above mentioned dose independent parameters, the area under the serum concentration-time curve showed a small (12%), but significantly higher increase than expected when the dosage regimen was increased from 200 mg X 2 to 400 mg X 2. This was, however, considered to be of no clinical relevance. Anticipating a 19% reduction of tiaprofenic acid bioavailability due to the intake of food, approximations of total body clearance and apparent volume of distribution can be made to 30.0 +/- 2.0 ml/min and 11.8 +/- 2.0 l, respectively. In spite of the small disproportional increase (12%) observed in the area under the serum concentration-time curve, it can be concluded that tiaprofenic acid shows a well defined pharmacokinetics in old people with acceptable interindividual variations and with a fast building-up to constant and predictable steady state levels within the dosage regimens investigated. A linear relationship was demonstrated between creatinine clearance and tiaprofenic acid total body clearance.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4026914 TI - Protein binding studies of furosemide and penbutolol. AB - Serum protein binding of furosemide and penbutolol, the active principles of Betasemid (Hoe 9358), was studied by equilibrium dialysis. Membranes from commercial dialysis tubes were used within commercially available cells. Serum drug and portion unbound in buffer were determined by quantitative thin-layer chromatography. In the range of 1-20 micrograms drug/ml serum, 96 +/- 0.3% of furosemide vs. 88 +/- 4% of penbutolol were bound to proteins. The same results were obtained, when the two substances simultaneously interacted with proteins. Thus, specific protein binding sites for both compounds were demonstrated. For both drugs, Scatchard plots revealed two classes of specific binding sites with statistical mean values/protein of 0.4 and 5 in the case of furosemide and 0.04 and 0.3 in the case of penbutolol. Binding energies were 27.6 and 19.6 kJ/mol furosemide vs. 31.5 and 23.9 kJ/mol penbutolol. Further, serum protein binding of furosemide was studied by ultrafiltration. A micropartition system MPS-1 was used. Results were the same as those from equilibrium dialysis. PMID- 4026915 TI - Plasma protein binding of salicylic acid, phenytoin, chlorpromazine, propranolol and pethidine using equilibrium dialysis and ultracentrifugation. AB - The in vitro plasma protein binding of phenytoin (diphenylhydantoin), salicylic acid, propranolol, pethidine (meperidine) and chlorpromazine was measured using an air-driven, bench-top ultracentrifuge and the results were compared with those obtained by equilibrium dialysis. For all drugs studied, except chlorpromazine, a significant correlation was found between the plasma binding results obtained by the two methods. However, only in the case of propranolol the actual binding values obtained by the two techniques were very similar. In the case of phenytoin, salicylic acid and pethidine, ultracentrifugation gave higher plasma binding values than equilibrium dialysis. Binding values obtained by the two methods for chlorpromazine were not correlated at all. This may be explained by binding of chlorpromazine to the very low density lipoprotein fraction which floats after ultracentrifugation. The described ultracentrifugation binding technique may be useful to rapidly measure the plasma binding of certain drugs in microsamples. PMID- 4026916 TI - Acute and subacute toxicity of 2,6-dimethyl-3,5-dimethoxycarbonyl-4-(o difluoromethoxyphenyl)-1 ,4-dihydropyridine (PP-1466). AB - The acute and subacute oral toxicity of 2,6-dimethyl-3,5-dimethoxycarbonyl-4-(o difluoromethoxyphenyl)-1,4 -dihydropyridine (PP-1466) was investigated in several animal species in comparison with nifedipine and nicardipine. A clear species difference in LD50 values was found in acute toxicity of PP-1466, and rabbits were the most sensitive between animal species used, then dogs, mice and rats in order. Prominent acute circulatory failure and associated secondary changes were noticed in toxic signs and autopsy findings. PP-1466 as well as nifedipine was apparently less toxic than nicardipine. In the subacute toxicity studies in rats, deaths occurred only in the 2000 mg/kg/d treated groups of both sexes of PP-1466 and nifedipine. Major changes in various observations and examinations were focussed on the cardiovascular system and liver. On the cardiovascular system, it was revealed as congestion and hemorrhage in the various organs and tissues on autopsy finding in dead rats during the test period. A dose-dependent increase in heart weight was observed in rats sacrificed at the termination of the test period. On the liver, it was revealed as a dose-dependent increase in liver weight, changes in liver lipid levels, changes in several serum biochemistry parameters, such as GOT, GPT and ALP (alkaline phosphatase) activities and lipid levels measured at the termination of the test period. These changes were toxicologically mild and functional except the autopsy findings in dead rats. Female rats were slightly more sensitive than males, and PP-1466 was slightly less toxic than nifedipine on subacute oral toxicity in rats. PMID- 4026917 TI - Prehepatic and hepatic first-pass metabolism of lorcainide in rats. AB - The systemic availability of 3H-lorcainide in rats was investigated following oral doses of 1.5 to 100 mg/kg. Systemic availability increased from 14 to about 40% following the lowest and highest dose, respectively. Doses higher than 60 mg/kg produced a less marked increase of the systemic availability. In rats with portacaval shunt following an oral dose of 1.5 or 7.5 mg/kg lorcainide a systemic availability of 47% was found, indicating substantial prehepatic first-pass metabolism of lorcainide. Systemic availability of total radioactivity was 53% in control rats and 90% in rats with portacaval shunt. Since the maximal systemic availability obtained by increasing the dose was found to be identical with that obtained in rats with portacaval shunt, it is suggested that increasing doses will saturate the presystemic metabolism in the liver but will not affect the fraction of the dose which is metabolized in the gut. PMID- 4026918 TI - Acetylcholine induces constriction of epicardial coronary arteries in anesthetized dogs after removal of endothelium. AB - The acetylcholine-induced relaxation of isolated coronary arteries is reversed to contraction in the absence of endothelium. The importance of endothelium for the regulation of coronary blood flow remains unclear. We thus tested the effects of acetylcholine on epicardial arteries and on coronary resistance vessels in situ in 8 anesthetized dogs. The left circumflex coronary artery was perfused at constant pressure. Epicardial vasomotion was evaluated by sonomicrometry, the vasomotion of coronary resistance vessels by calculated end-diastolic resistance. Acetylcholine (1 microgram/kg/min i.c.) decreased epicardial resistance by 8.6 +/ 1.6% and end-diastolic resistance by 65.8 +/- 6.3%. The epicardial coronary segment was perfused with distilled water for 65 +/- 5 s to denude it of endothelium. After removal of epicardial endothelium, the decrease in end diastolic resistance caused by acetylcholine was unchanged (59.6 +/- 1.2%); however, epicardial resistance was increased by 7.7 +/- 1.7%. Application of glyceryl trinitrate (5 micrograms/kg/min i.c.) induced a similar decrease of epicardial resistance before and after removal of endothelium:7.9 +/- 1.4 and 6.2 +/- 1.9%, respectively. We conclude that acetylcholine-induced dilation of epicardial coronary arteries is endothelium-dependent in vivo. However, the constriction of epicardial coronary arteries in the absence of endothelium is insufficient to reduce blood flow and to induce myocardial ischemia. PMID- 4026919 TI - [Properties and efficacy of a human immunoglobulin M preparation for intravenous administration]. AB - From Cohn fraction III a new immunoglobulin (Ig) preparation (Pentaglobin) was prepared. This preparation contains 72% IgG and is enriched in IgM (12%) and IgA (16%). Due to a treatment with beta-propiolactone it is suitable for intravenous application. This IgM-enriched immunoglobulin preparation is prominent in high antibody titers (passive hemagglutination) against gram-negative as well as gram positive germs and shows significantly higher efficacy in mouse protection tests than intravenous standard IgG. The high IgM content of this preparation in particular is responsible for the binding of bacterial antigens. Thus a marked advancement in the treatment of bacterial infections is to be expected by this new intravenously tolerable immunoglobulin preparation. PMID- 4026920 TI - Postnatal development of young rats following the treatment of the dams with sodium salicylate during late periods of pregnancy. AB - Female albino rats were treated with sodium salicylate dissolved in tap water orally by intubation. The first group received daily doses of 25, 75 or 150 mg/kg from day 15 through day 20 of pregnancy. The second group received daily doses of 4.2, 12.5 or 25 mg/kg on day 20 and on day 21, i.e. the day of parturition. Administration of the intermediate and high doses caused a marked increase in the mortality rates of the young animals. However, the development of the surviving young rats was similar to the controls and no change in behaviour was noted. PMID- 4026921 TI - Comparison of various pharmaceutical preparations of prednicarbate after repeated topical administration to the skin of rats. AB - The following pharmaceutical preparations of prednicarbate (Hoe 777) were tested: fatty ointment 0.1% and 0.25%, ointment 0.1% and 0.25%, cream 0.1% and 0.25%, solution 0.25%. These pharmaceutical preparations were applied 10 times to the shorn back of male Sprague-Dawley rats. After sacrifice the following parameters were recorded: body weight, skin thickness as well as ultimate load, ultimate strain, tensile strength and modulus of elasticity of excised skin strips. Soluble fractions of collagen (soluble in 0.15 and 0.5 molar NaCl solution and in citrate buffer) and insoluble collagen as well as total collagen/g fresh weight were determined. The values of the treated animals were compared with the values of untreated animals and animals treated with the individual base only. As found in earlier studies prednicarbate induced a slight decrease of body weight and skin thickness. Ultimate extension and ultimate load were only barely changed. There was, however, a dose-dependent increase of modulus of elasticity and tensile strength, due to treatment with prednicarbate. Simultaneously, an increase on insoluble collagen and of total collagen per g fresh weight was noted. These results confirm previous findings, indicating a positive correlation between tensile strength and modulus of elasticity of connective tissue with the content of insoluble collagen. The effects of ointment, fatty ointment and cream are very similar, nevertheless, they depend on the type of formulation applied. In the case of prednicarbate solution the dependence of the effects upon the formulation used is very obvious. The increase of tensile strength and modulus of elasticity as well as of insoluble collagen show that very impressively. PMID- 4026922 TI - [Rectal absorption of steroids]. AB - The investigations were designed to evaluate the systemic absorption of two steroids from suppositories. The suppositories containing either 3H hydrocortisone (1 mg) or 3H-prednisolone-21-hexanoate (1 mg) were administered to a group of 4 baboons restrained in chairs. The levels of radio-activity in the plasma and urine were measured up to 120 h following rectal administration, and these levels were compared with those of a subsequent intravenous administration (1 mg each). The results show that both hydrocortisone (H) and prednisolone-21 hexanoate (P) are rapidly (tmax = 2-3 h) and significantly (H: 60-78%, P: 47-58%) absorbed from suppositories and thus can also cause systemic effects. PMID- 4026923 TI - In vitro effects of ureidopenicillins on human polymorphonuclear leukocytes. AB - The in vitro effects of mezlocillin, azlocillin and piperacillin on chemotaxis and adhesivity of human leukocytes were comparatively studied. After incubation with all these antibiotics, chemotactic and adhesivity counts were similar to those of the antibiotic-free cells. Scanning electron microscope examination showed enlargement of surface and length measurements after incubation with azlocillin (P less than 0.005 and P less than 0.001) and mezlocillin (P greater than 0.05 and P less than 0.05), while piperacillin produced no alteration. These findings could provide additional information in the study of leukocyte/antibiotics interactions. PMID- 4026924 TI - [The bioavailability of combination preparations of acetylsalicylic acid and codeine phosphate]. AB - Plasma levels time curves of acetylsalicylic acid, salicylic acid, salicyluric acid and codeine were monitored after intravenous, oral and rectal application (single dose) of preparations containing acetylsalicylic acid and codeine. The mean absolute bioavailability of acetylsalicylic acid was 68% after oral application and 60% after rectal application. The corresponding bioavailability data of codeine were 59% and 63%, respectively. PMID- 4026925 TI - Pharmacokinetics and bioavailability of suprofen injection solution after intravenous application versus capsules on six healthy male volunteers. AB - In a three-way cross-over study six healthy male volunteers received intravenously 50 mg and 100 mg suprofen as a bolus injection and orally 200 mg as one capsule. The plasma level curves could be fitted to a two-compartimental model by means of the computer program NONLIN. The pharmacokinetic parameter estimates did not show dose dependency. The absolute bioavailability of suprofen taken as one capsule was 92.2% based on AUC-values and did not indicate a first pass effect. The plasma input curve was determined by point-area deconvolution. Assuming first order input a half-life of 23 min could be derived based on point area deconvolution. Different dissolution models based on USP XX are discussed in relation to the kinetic data generated. PMID- 4026926 TI - Binding of tiaprofenic acid to human sera and isolated serum proteins. AB - The serum protein binding of tiaprofenic acid (Surgam) has been investigated in vitro by equilibrium dialysis in a physiological buffer of pH 7.40 with a 14C labelled tiaprofenic acid isotope. The stability of labelled and unlabelled tiaprofenic acid was good during dialysis and an irregular distribution of 6% impurities in the 14C-labelled tiaprofenic acid isotope preparation was corrected for. No differences were found between elderly (74 +/- 4 yrs) and young (32 +/- 6 yrs) individuals, both groups showing a serum protein binding of tiaprofenic acid of 99.0 +/- 0.15%. However, patients with impaired renal function (creatinine clearance 24 +/- 8 ml/min) showed a significantly lower binding of 98.5 +/- 0.35%. Albumin was identified as the main tiaprofenic acid binding protein in human serum with a high affinity binding site characterized by an in vitro dissociation constant, KD, of 3.8 x 10(-6) mol/l and a number of available binding sites, n, of 0.34. Tiaprofenic acid was found not to be displaced from serum protein binding sites by other highly bound drugs. It is concluded that tiaprofenic acid protein binding is characterized by small interindividual variations, but that the decreased binding of tiaprofenic acid in patients with renal failure should be paid some attention to. PMID- 4026928 TI - Comparative pharmacokinetics of doxycycline and oxytetracycline in patients with hyperlipidemia. AB - This study examines the pharmacokinetics of lipophilic drug doxycycline (Vibramycin) and water-soluble antibiotic oxytetracycline hydrochloride (Oxyterracyna) in patients with hyperlipidemia type IIa and type IV according to Fredrickson. Antibiotics were administered orally as a single dose and determined in plasma by a fluorimetric method. The calculations were performed by aid of a computer. Increased concentrations of doxycycline were found; they were higher in type IIa, as compared with type IV. Area under the curve (AUC) and peak concentrations as well as rate constant for elimination in subjects with type IV were significantly elevated; volumes of distribution and total body clearance were markedly diminished. Decreased concentrations of oxytetracycline, area under the curve, peak concentration and rate constant for elimination were observed in patients with type IV. In both types of hyperlipidemia volume of distribution was increased and half-life in patients with type IV was significantly prolonged. The findings show that hyperlipidemia can be an important factor of drug action. Alterations of pharmacokinetics of lipophilic doxycycline and hydrophilic oxytetracycline were contrasting. PMID- 4026927 TI - Sulfadiazine versus sulfafurazole excretion in urine and risk of crystallization in children with conventional dosage regimen. AB - The excretion of sulfadiazine (Adiazin) (n = 8) and sulfafurazole (n = 8) in urine and the risk of crystallization were compared in children, 3-14 years of age. They suffered from acute urinary tract infection and were treated with conventional dosage regimen of either of the sulfonamides. Sulfadiazine (4 mg/kg twice daily, the initial dose 8 mg/kg) produced active serum drug levels which in relation to antimicrobial activity of sulphonamides corresponded to 25-30% of those obtained with sulfafurazole (50 mg/kg four times a day). In urine the corresponding sulfadiazine levels were 21-61% of those of sulfafurazole. In none of the urine fractions sulfadiazine concentrations exceeded the theoretical drug solubility but sulfafurazole exceeded this risk limit altogether in 4 urine fractions (2 patients). Urine sediment showed, however, sulfonamide crystals in only one urine fraction of the sulfafurazole group. The results suggest that with conventional dosage regimen sulfafurazole produces higher effective serum and urine drug concentrations in children than sulfadiazine but shows a higher risk to crystallize in urine. PMID- 4026929 TI - Single-dose pharmacokinetics of fenquizone in healthy volunteers. AB - A pharmacokinetic study of fenquizone (Idrolone), a thiazide-like diuretic, was conducted with single oral doses in 6 healthy volunteers. The substance thus administered was readily absorbed from the gut, with peak plasma levels being detected on average at 3 h after dosing; after that, plasma concentrations of fenquizone decreased biexponentially in a pattern fitting an open two-compartment model. Plasma half-life values were 1 h for phase alpha and 17 h for phase beta. The half-life calculated from urinary concentrations was 18 h. The apparent distribution volume for phase beta was 686 l; renal clearance was 220 ml/min, and the absorption constant (Ka) was 1055 h-1. Cumulative urinary excretion accounted for 53.1% of the administered dose in 72 h. Thus the pharmacokinetic profile of fenquizone was that of an "intermediate-acting" diuretic about half-way between the short-acting hydrochlorothiazide, chlorothiazide and furosemide and the long acting chlorthalidone. In summation, fenquizone is described as a low-dosage diuretic apparently not conducive to accumulation; its pharmacokinetic profile qualifies the product particularly well for maintenance therapy, such as is needed for the management of essential hypertension, both as sole medication and in fixed-ratio combination with beta-blockers, and at any rate with once-a-day administration. PMID- 4026930 TI - Hearing aids: future prospects. PMID- 4026931 TI - Ageism. A negative view of the aged. PMID- 4026932 TI - Effect of post-mortem time on the biochemical composition of coronary arteries. AB - The effects of post-mortem autolysis on the biochemical composition of coronary intima-medias were studied by keeping the coronary arteries of 25 slaughterhouse pigs at +4 degrees C for periods up to 7 days. The samples were analysed for DNA, total protein, collagen, glycosaminoglycans (GAGs), free and esterified cholesterol, triglycerides, phospholipid fractions, and fatty acid composition in various lipid classes. The content of sulphated GAGs decreased steadily, whereas that of hyaluronic acid remained unchanged. These alterations led to a significant decrease in the content of total GAGs and to an increase in the percentage of hyaluronic acid in total GAGs. The results indicate a continuous post-mortem degradation of arterial proteoglycans. After 7 days storage, there was a significant increase in the content of free fatty acids, and the composition of this fraction was changed by increases in the relative amounts of oleic and linoleic acids. These changes were accompanied by an increase in lysolecithin and a decrease in lecithin, which suggests a post-mortem action of arterial phospholipases. PMID- 4026933 TI - Sulfated glycosaminoglycans in cultured endothelial cells from capillaries and large vessels of human and bovine origin. AB - The [35S]glycosaminoglycans ([35S]GAG) synthesized by capillary endothelial cells were analyzed and compared to GAG synthesized by endothelial cells cultured from 4 larger vessels. Two separate cultures of endothelial cells were established from bovine fat capillaries and from 4 larger vessels of human origin (umbilical vein) and bovine origin (pulmonary artery, pulmonary vein and aorta). After incubation with 35SO4 for 72 h, the [35S]glycosaminoglycans (GAG) composition of the media, pericellular and cellular fractions of each culture were determined by selective degradation with nitrous acid, chondroitinase ABC and chondroitinase AC. All endothelial cells produced large amounts of [35S]GAG with increased proportions of heparinoids (heparan sulfate and heparin) in the cellular and pericellular fractions. Each culture showed a distinct distribution of [35S]GAG in the media, pericellular and cellular fractions with several specific differences found among the 5 cultures. The differences in GAG content were confirmed in a second group of separate cultures from each of the 5 vessels indicating that, although having several features of GAG metabolism in common, each endothelial cell culture demonstrated a characteristic complement of synthesized, secreted and cell surface-sulfated glycosaminoglycans. PMID- 4026934 TI - Cholesterol-rich micelles in human plasma. PMID- 4026935 TI - The biochemical composition of haemodynamically stressed vascular tissue. Part 1. The lipid, calcium and DNA concentrations in experimental arteriovenous fistulae. AB - Experimental arteriovenous anastomoses were fashioned between the external jugular vein and the common carotid artery in sheep. The altered haemodynamics induced morphological changes, particularly in the venous tissue. Many of these alterations were similar to those seen in human atherosclerosis. Some of the biochemical compositional changes that occurred in such tissues are reported here. Whilst the serum cholesterol level was unaltered during the post-operative period, there was an increase in the free and total cholesterol content of the experimental vein but not of the artery. The serum triglyceride level approximately doubled but the tissue triglyceride rose on only the arterial side of the shunt. There was a decrease in the triglyceride level in the experimental vein. The calcium content showed a slight decrease in both experimental arterial and venous tissue although the drop was not statistically significant. The DNA concentration which was assayed so as to provide a measure of the cell density was about 1.5-2.0 times higher in the arterial tissue. PMID- 4026936 TI - Particle size distribution of high density lipoproteins as a function of plasma triglyceride concentration in human subjects. AB - Polyacrylamide gradient gel electrophoresis has been used to examine the particle size distribution of high density lipoproteins (HDL) in human subjects with a wide range of plasma triglyceride concentrations. In studies of groups of both male and female subjects, it was confirmed that the concentration of HDL cholesterol decreases with increasing plasma triglyceride concentration. The HDL fraction from subjects with elevated concentrations of plasma triglyceride was depleted of cholesteryl ester and enriched in triglyceride. It was also confirmed that the proportion of HDL subfraction 2 (HDL2) declines as the plasma triglyceride increases. A new finding was that there were also significant changes in the size of particles in HDL subfraction 3 (HDL3). At low concentrations of plasma triglyceride the predominant subpopulation of HDL3 comprised particles of mean radius 4.3 nm. As the triglyceride concentration increased, however, there was a progressive appearance of HDL3 particles of radius 3.9 nm; in plasma samples with the highest concentrations of triglyceride there was an almost complete disappearance of the 4.3-nm particles, with the population of 3.9-nm particles now predominant. PMID- 4026937 TI - The effect of selective breeding on the development of coronary atherosclerosis in WHHL rabbits. An animal model for familial hypercholesterolemia. AB - To increase the incidence of coronary atherosclerosis in Watanabe heritable hyperlipidemic (WHHL) rabbits, an animal model for familial hypercholesterolemia, selective breeding has been carried out. The results obtained are as follows: The incidence of coronary atherosclerosis before selective breeding was 21.8%, whereas that after the breeding was 58.9% (average values for rabbits between 4 and 12 months old), showing that the incidence of coronary atherosclerosis can be increased by an appropriate breeding technique. With respect to the relationships between parents and offspring, if parents had coronary atherosclerosis, then the incidence of the disease in the offspring was 83.3%; therefore the disease was strongly heritable. The mean total cholesterol (TC) and triglyceride (TG) levels of the colony before selective breeding were 579 +/- 163 mg/dl and 471 +/- 144 mg/dl, respectively, while those after the breeding were 665 +/- 151 mg/dl and 603 +/- 178 mg/dl; serum lipid levels increased in parallel with incidence of coronary atherosclerosis. The earliest development of coronary atherosclerosis in the colony after selective breeding was found in 4-month-old rabbits and the whole colony suffered from the disease at 18 months of age. PMID- 4026938 TI - High-affinity uptake and degradation of acetylated low density lipoprotein by confluent human vascular endothelial cells. AB - Confluent human vascular endothelial cells take up and degrade acetylated low density lipoproteins (Ac-LDL) via a high-affinity binding process, comparable to that for native LDL. The degradation of 125I-labelled Ac-LDL by endothelial cells was inhibited by the addition of unlabelled Ac-LDL but not by the addition of unlabelled LDL. Similarly, the degradation of 125I-labelled LDL could be inhibited by unlabelled LDL but not by unlabelled Ac-LDL. Unlabelled apolipoprotein E-free HDL did not compete with the degradation of either 125I labelled LDL or Ac-LDL. Electron microscopical studies, using gold-labelled LDL and gold-labelled Ac-LDL, showed that at 4 degrees C both LDL and Ac-LDL bind to indented regions of the endothelial cell plasma membrane. At 37 degrees C both LDL and Ac-LDL were taken up and associated with lysosomes. Although morphologically identical, we conclude that the binding of LDL and Ac-LDL to human endothelial cells proceeds via 2 different high-affinity receptors. The uptake and degradation of Ac-LDL by human endothelial cells was about 25 and 15%, respectively, of that of native LDL. The uptake and degradation of either LDL or Ac-LDL did not lead to a massive increase in cellular cholesterol content. PMID- 4026939 TI - Chemical composition and physical state of lipid deposits in atherosclerosis. AB - The composition, morphology, and physical properties of lipids in atherosclerotic lesions from human aortas were studied in order to elucidate the factors for the accumulation of cholesterol and its esters in the vessel wall. Lesions were classified histologically into 3 groups: fatty streak, fibrous plaque, and advanced plaque. The relative lipid composition of the lesions was plotted on the phase diagram of the 3 major lipids: cholesterol, cholesteryl ester, and phospholipid. Early fatty streaks had compositions within the 2-phase zone with a cholesterol-phospholipid liquid crystalline phase and a cholesteryl ester oily phase. Advanced fatty streaks and fibro-fatty plaques fell within the 3-phase zone with excess free cholesterol. Advanced plaques also had an average lipid composition within the 3-phase zone, but with a larger excess of free cholesterol. From the lipid-chemical point of view there is a continuous progression from early fatty streaks through advanced fatty streaks and fibro fatty plaques to advanced plaques. In fatty streaks the cholesteryl esters accumulate in the form of isotropic and anisotropic droplets. The latter are in the smectic liquid crystalline state with the molecules arranged in layers and have surfaces that are spherical and smooth. Fibrous and advanced plaques showed beside droplets also amorphous lipids and cholesterol monohydrate crystals. Some of the amorphous lipids were solid up to about 45 degrees C and exhibited a smectic phase at cooling, indicating cholesteryl esters as the major component. The transition temperatures of high-melting cholesteryl esters, e.g. palmitate, are depressed by low-melting ones. Most of the triglycerides are present in the cholesteryl ester droplets and abolish the cholesteric liquid crystalline phase. PMID- 4026940 TI - [Toxicological characteristics of a methylacetylene-allene fraction]. PMID- 4026941 TI - Management of the heel spur (syndrome). PMID- 4026942 TI - A decision tree approach to psychodiagnosis. The diagnosis of abnormal behaviour. PMID- 4026943 TI - The distribution of nuclear mass, volume and dimensions. AB - Our own measurements and a review of measurements presented in the literature showed that the mass, volume and dimensions of cell nuclei are distributed with a skew towards higher values, a distribution that can best be described as lognormal. The practical consequences of this finding suggest that the measurements of mass and of size should be plotted on a logarithmic scale while DNA values are appropriately presented on a linear scale. The distribution of DNA values of normal cells represents errors introduced by random disturbances in preparations and measurements. PMID- 4026944 TI - Ploidy pattern analysis. Statistical considerations. AB - Availability of large data sets of ploidy measurements makes it possible to study ploidy patterns for the diagnostic and prognostic clues they can provide. Appropriate statistical analyses can improve the accuracy and precision of these studies. Such statistical analyses include considerations of sample size requirements for the detection of different types of deviations from normal, analyses of sources of variability in ploidy patterns and assessment of the probabilities of both types of possible errors in patient classification. The advantages of statistical assessment in the classification of ploidy patterns associated with diagnostic categories are discussed in the context of these considerations. PMID- 4026945 TI - Test statistics for detecting aneuploidy and hyperdiploidy. AB - Possible approaches to the analytical evaluation of ploidy patterns are discussed and two specific problems are considered: detection of early onset of aneuploidy and detection of moderate hyperdiploidy. A statistical model for a euploid DNA pattern is formulated in terms of a mixture distribution. A test statistic for detecting deviations from this pattern is defined, and its performance is evaluated for simulated data representing differing degrees of severity of aneuploidy. An analysis based on a discriminant function using order statistics of the sample cumulative distribution functions is proposed for detecting hyperdiploidy. This procedure has the advantage of being relatively distribution free; its performance is evaluated for simulated data and is compared with that of its classical counterparts. Although the results reported are only preliminary, they indicate that tailor-made statistical analyses can provide early detection of aneuploidy and hyperdiploidy with known and acceptable error rates using clinically reasonable sample sizes. PMID- 4026946 TI - Multinomial distributions in ploidy analysis. AB - Ploidy patterns can be summarized in the form of a vector of proportions representing the frequency of occurrence of DNA contents in specified intervals. Data represented in this way can be analyzed statistically using the multinomial distribution. Properties of the multinomial distribution and computational difficulties that arise in its application are considered. Special problems involved in formulating hypothesis tests and confidence regions for multivariate discrete distributions are discussed in the context of evaluating vectors of proportions representing DNA ploidy patterns. Construction of tailor-made critical regions for detecting specific types of deviations from normal ploidy patterns is proposed, and a detailed example is given. In this example, two critical regions are compared: a standard critical region, consisting of cases whose probability of occurrence is small, and a diagnostic critical region, consisting of cases considered to be clinically indicative of abnormality. Advantages of the diagnostic critical region are noted. PMID- 4026947 TI - Cytophotometry of breast carcinoma. Acridine-orange DNA microfluorimetry with Giemsa counterstain. AB - Investigations have suggested that a correlation exists between DNA ploidy levels and prognosis in human breast carcinoma. Nuclear DNA content can be studied by flow cytometry or cytophotometric analysis. While both methods yield comparable results for DNA distribution, cytophotometry has the advantage of permitting both quantitative cell measurements and cytomorphologic identification of tumor cells. Microfluorimetric analysis of nuclear DNA content was carried out on acridine orange-stained imprint smears of malignant breast tumors, with the DNA values plotted as a histogram distribution. Quantitative fluorescence measurements of breast carcinoma cells using the acridine-orange stain appeared to be a fairly rapid and simple method for DNA determination as compared to Feulgen DNA analysis. Following cytometric measurements, imprint smears were counterstained by the Giemsa stain and examined by cytomorphologic criteria. With the Giemsa counterstain, the same cytologic preparation could be studied both by quantitative cell measurements and by conventional cytomorphologic criteria. Results are illustrated, and possible implications of the use of this method in the study of tumor behavior and the diagnosis by cytologic methods are discussed. PMID- 4026948 TI - Ploidy measurements by high-resolution cytometry. AB - Technology has made DNA ploidy assessment a clinically and economically feasible procedure, 30 years after its clinical potential was established. This paper reviews the history of ploidy measurements, DNA cytophotometry, DNA interpretation and the prognostic value of nuclear DNA analysis in various anatomic sites. Emphasis is placed on static high-resolution cytometry, not flow cytometric methods, with a description given of the systems for rapid DNA cytometry developed as part of the TICAS Project at the University of Chicago. PMID- 4026949 TI - Ploidy levels in nonneoplastic and neoplastic thyroid cells. AB - DNA levels in nonneoplastic and neoplastic human thyroid cells were studied by slide-cytophotometric and flow-cytophotometric techniques. Normal epithelial thyroid cells and cells from nonneoplastic thyroid disorders, i.e., toxic goiter, colloid goiter and chronic lymphocytic thyroiditis, had euploid (diploid, polyploid) DNA levels. The same was the case for benign tumors. Malignant tumors had either euploid DNA levels, indistinguishable from those in nonneoplastic and benign neoplastic cell populations, or aneuploid DNA levels. Taking into account the histopathologic diagnosis, clinical course and DNA level, the results indicate that DNA measurements in thyroid gland lesions are of limited diagnostic help but may contribute valuable prognostic information. To obtain representative and accurate DNA measurements, combined slide-cytophotometric and flow cytophotometric techniques should be used. PMID- 4026950 TI - Interocular transfer in the pigeon after lesions of the dorsal supraoptic decussation. AB - Pigeons trained to discriminate between visual stimuli in a key-pecking task normally show excellent interocular transfer of training (IOT) when trained with only one eye and then tested with the 'naive' eye. When the dorsal supraoptic decussation (DSO) was sectioned and pigeons were then trained monocularly to peck at keys in an interocular transfer experiment, they failed to show normal IOT of a simultaneous horizontal-vertical discrimination. In contrast, another group of pigeons, in which the DSO was sectioned after they had already learned the discrimination with one eye covered, showed excellent IOT postoperatively when the blindfold was moved to the other eye. Since the pigeon uses the normally binocular portion of its retina to scan the discriminative stimuli in a key pecking task and the DSO carries converging binocular input from the retinorecipient zone of the thalamus to the visual Wulst, the results suggest that IOT in the pigeon is the simple consequence of information reaching both hemispheres from a single eye via converging binocular pathways. Thus, cutting the DSO before training with the first eye eliminates IOT whereas cutting it after training with the first eye does not (since information has already reached the two hemispheres from the normally binocular portion of that eye). These findings complement earlier work showing that IOT is absent in normal pigeons in those situations in which they scan the discriminative stimuli with the monocular portion of their visual fields. PMID- 4026951 TI - Striatal influence on ingestive behaviour in the cat. AB - In freely moving cats with chronically implanted electrodes an analysis was made of the effects on feeding behaviour of low-frequency long-duration stimulation of the caudate nucleus, the substantia nigra and the globus pallidus. In all 3 structures a significant reduction of food intake was observed and in the pallidus this reached the point of a complete block of feeding. The effects were always limited to the period of stimulation. At the end of stimulation the animals recovered and took in food quantities equal to those of controls. The results are interpreted on the basis of reciprocal connections between the basal ganglia and the hypothalamus; the role of the striatum on the selection of certain movements and its possible involvement in behaviour is also discussed. PMID- 4026952 TI - Comparative characteristics of unit activity in the prefrontal and parietal areas during delayed performance in monkeys. AB - Neuronal mechanisms of prefrontal and parietal areas were compared in 3 monkeys during delayed performance. Spatioselective neurons were found in both areas in question. In the prefrontal cortex, they constitute 28% of all units sampled and in the parietal cortex they account for 21%. For the prefrontal area, spatial selectivity was particularly great during the delay (8%), and in the parietal area during the cue display (9%). During the delay, however, spatioselective parietal neurons accounted for 4% of all units sampled, i.e. their number was half that in the prefrontal area. The prefrontal cortex appears to play a major role in short-term memory proper, whereas the parietal area is more involved in assessing spatial relationships of emerging sensory stimuli. Spatioselective neurons of both areas were heterogeneous in their functions. Activity of some (11% in the prefrontal and 10% in the parietal area) was related only to the cue location. Activity of others (13% in the prefrontal cortex and 8% in the parietal cortex) was moreover coupled with the forthcoming movement. With lengthening of the delay, units related to the established temporal stereotype and some labile units which quickly rearranged to a new temporal task were recorded. Thus association area neurons reflect two concurrent processes linked with spatial and temporal memories. During cue displays, it is not only their spatial location that is described, but also a future motor act with its temporal and spatial properties programmed. PMID- 4026953 TI - Visuomotor strategies in pattern discrimination learning in rats. AB - Normal rats were trained on a series of visual tilt discriminations ordered from simple to difficult to measure their angular difference thresholds. The stereotyped visuomotor running pattern which the animal made was recorded for all angular differences binocularly and whilst the animal was monocularly patched. The results show that the running pattern does not reflect visual guidance strategies and can produce a visual field bias for the field ipsilateral to the preferred approach side. PMID- 4026954 TI - Aldehyde dehydrogenase content and composition of human liver. AB - Human liver contains only four proteins which catalyze dehydrogenation of acetaldehyde; two of these are tetrameric with MW of 220,000 and are structurally related. These enzymes were purified previously to homogeneity and are now known as the cytoplasmic E1 and mitochondrial E2. The other two proteins do not appear to be structurally related to E1 and E2. The recently isolated E4 enzyme is a dimer of MW of ca. 175,000; the E3 may be a polymorphic enzyme. The Enzyme Commission classification for E1 and E2 is EC 1.2.1.3, that for E4 is at present uncertain since its Michaelis constants for short chain aldehydes are high, making it unlikely that these would be its natural substrates. The relationship between E3 and E4 is also uncertain. Employing a suitably designed assay, E1 and E2 are assayed as "low Km" enzymes while E3 and E4 are assayed as "high Km" enzymes. Therefore by employing such an assay, combined with electrofocusing procedure, an assessment of enzyme content and composition of aldehyde dehydrogenase in human liver can be made. PMID- 4026955 TI - Aldehyde dehydrogenase polymorphism and alcohol metabolism in alcoholics. AB - Significant differences in the incidence of aldehyde dehydrogenase isozyme I deficiency were observed between healthy controls and alcoholics in Japan. Only about 5% of alcoholics were found deficient as compared to about 42% in the normal healthy population. Blood acetaldehyde level after alcohol drinking was also found significantly higher in deficient subjects than in individuals without deficiency. Among alcoholics, deficient subjects showed relatively less elevated blood acetaldehyde levels. When two districts in Japan were compared, per capita alcohol consumption correlated with the frequency of isozyme deficiency. Higher percentage of aldehyde dehydrogenase isozyme deficiency was associated with lower per capita alcohol consumption. Thus, individuals deficient in aldehyde dehydrogenase isozyme may consume less alcohol. PMID- 4026956 TI - Polymorphism of aldehyde dehydrogenase and ethanol elimination. AB - The influence of polymorphism of aldehyde dehydrogenase (ALDH) on ethanol elimination was investigated. Japanese healthy male volunteers were divided into two groups, i.e., a normal ALDH group of 52 subjects with the low Km isozyme of ALDH, and a deficient group of 48 subjects without it. The subjects of the normal group were given 0.4, 0.8, 1.2, 1.6 or 2.0 g/kg of ethanol, while those in the deficient group ingested 0.4, 0.8 or 1.2 g/kg of ethanol. Widmark's factors (beta 60, Co and r) and ethanol elimination rate (ER) were compared between the two groups. In the deficient group, beta 60 and ER were not clearly elevated with the increase of ethanol dose, while those in the normal ALDH group increased depending on the blood ethanol level. Blood acetaldehyde level was elevated with the increase of the ethanol dose in the deficient group, but not in the normal group. In the experiment of the repeated ingestion of ethanol in the deficient group, the second peak of blood acetaldehyde level was lower than that of the first one. PMID- 4026957 TI - Regulation of the formation of stable adducts between acetaldehyde and blood proteins. AB - Recent reports have described increased levels of a fast-moving hemoglobin (Hb) fraction in alcoholic patients and formation in vitro of stable adducts between acetaldehyde and Hb as well as between acetaldehyde and albumin. In the present study, we have found that factors other than acetaldehyde concentration can influence the rate of stable adduct formation. HbAo was purified and its 2,3 diPglycerate removed by dialysis. Under anaerobic condition and at 37 degrees, acetaldehyde (5 microM) reacted with deoxyHbAo to form 0.26 +/- 0.02 (+/- SEM) nmol of stable adduct/149 nmol Hb in 2 hr. By comparison, acetaldehyde reacted more slowly with oxyHbAo and carbonylHbAo; the rates were 0.21 +/- 0.01 (p less than 0.001) and 0.18 +/- nmol/149 nmol Hb/2 hr (p less than 0.001), respectively. Pyridoxal 5'-phosphate (50-500 microM), under anaerobic condition, inhibited by 36-56 percent the irreversible binding of acetaldehyde to deoxyHbAo. Ascorbic acid (2.5-10 mM) increased by 31-46 percent (p less than 0.001) the irreversible binding of acetaldehyde to human serum albumin and by 8-10 percent (p less than 0.05) the irreversible reaction of acetaldehyde with serum proteins. We conclude that the nonenzymatic binding of acetaldehyde to Hb, human serum albumin and serum proteins is influenced by factors other than acetaldehyde concentration. These factors include oxygen tension, pyridoxal 5'-phosphate and ascorbic acid. Among these factors, oxygen tension may be the most important in vivo. PMID- 4026958 TI - The measurement of 2,3-butanediol and 1,2-propanediol in "flushing" and "non flushing" Japanese. AB - Seven Japanese medical students, three "flushers" and four "non-flushers," were given 0.5 g ethanol/kg body weight PO in an attempt to assess whether elevated body acetaldehyde can account for 2,3-butanediol production in humans. Blood was taken from the anticubital vein immediately prior to, 30, 60, 90, and 120 min after ingestion of ethanol. No difference in the two groups was observed in 2,3 butanediol or in 1,2-propanediol. Measured 1,2-propanediol was in the normal range in both groups. No 2,3-butanediol was detected in any of the subjects. PMID- 4026959 TI - Decreased Fc-receptor binding in human monocytes exposed to ethanol in vitro. AB - Human blood monocytes were incubated with or without ethanol (14 mM-220 mM, initial concentration) in non-sealed wells in an atmosphere of 5% CO2 in air for various time periods. The actual ethanol concentration was assayed in the media at the beginning and at the end of each incubation period. No change in ethanol content was found after 5 or 15 min incubation, while a reduction to about 70% of the initial concentration was observed after 6 hr incubation. Binding of IgG opsonized particles to the Fc-receptors was tested after ethanol exposure of the cells. An initial concentration of 14 or 28 mM ethanol caused no difference from controls, neither did incubation in 55 mM ethanol for 5 min. Monocyte incubated in 55 mM ethanol for 15 min showed reduced binding of particles, and further reduction was obtained by increasing the ethanol concentration. Six hr incubation in 55 mM ethanol caused no further reduction in binding capacity. Reduced binding of test particles to Fc-receptors after ethanol incubation was demonstrated with variable amounts of test particles, as well as variable length of the binding assay period. There was no change in viability, morphology or spreading ability of the monocytes after ethanol treatment. PMID- 4026961 TI - First pass metabolism of ethanol: an important determinant of blood levels after alcohol consumption. AB - Alcohol consumption by rats fed ethanol-containing liquid diets is considerably greater than the measured rate of ethanol elimination from the blood, suggesting that a significant fraction of the alcohol ingested does not enter the systemic circulation. To assess the possibility of a first pass metabolism of ethanol, we compared the areas under the blood ethanol concentration curves after administration of various doses through various routes in alcohol-fed and control rats. In both groups, blood ethanol concentrations were significantly lower after intragastric than after intraportal or intravenous (femoral) administrations and, to a lesser extent, than after an intraduodenal dose. By contrast, the rise in blood acetate, a product of ethanol oxidation, was faster after intragastric administration. Moreover, absorption of the ethanol dose was virtually complete at the time of ethanol disappearance from the blood. The fraction of the dose that did not enter the systemic circulation was proportionally greater with the smaller doses. These results indicate that there is a significant first pass metabolism of ethanol which takes place in the gastrointestinal tract and particularly in the stomach, where alcohol dehydrogenase (ADH) activity is the highest. Chronic alcohol administration decreased ADH activity (probably secondary to gastric mucosal injury) and also decreased the magnitude of the first pass metabolism. The amount of ethanol ingested which does not enter the systemic circulation accounts for the apparent dissociation between alcohol consumption, blood ethanol levels and rate of blood ethanol elimination in alcohol-fed animals. PMID- 4026960 TI - Effects of ethanol on platelet function. AB - To obtain evidence for an ethanol mediated disruption of hemostasis we compared the effects of acute and chronic ethanol ingestion on platelet reactivity. Since ADP may be important for hemostasis in vivo it was used to induce platelet aggregation in platelet-rich plasma. Thromboxane B2 (TXB2) formed during the aggregation was measured by radioimmunoassay. Ethanol (1.5 g/kg) given to 8 healthy non-alcoholic male volunteers increased platelet reactivity to ADP and the associated TXB2 formation rose from 289 +/- 60 (mean +/- SE) to 984 +/- 263 fmol/10(7) platelets (p less than 0.025). The effects lasted for as long as ethanol was present in blood. In 13 non-cirrhotic male alcoholics the withdrawal of ethanol caused a 4-fold increase in TXB2 formation within one week but the basal levels before ethanol withdrawal were the same as in controls. These findings are discussed in relation to the higher risk of brain infarction seen in alcoholics and even associated with binge drinking. Further studies are needed to establish the effects of ethanol on prostacyclin formation. PMID- 4026962 TI - Varying rates of alcohol metabolism in relation to detoxification medication. AB - Fifteen patients admitted for alcohol dependency had serial blood alcohol levels drawn. The rate of metabolism was calculated a number of different ways and this was compared to the amount of Librium required for the initial period of withdrawal. It was found that the alcoholics' average metabolism was 26.6 mg%/hour. Although there was a tendency for those with high initial blood alcohol levels to have faster metabolisms, there was not a significant correlation between the two features. There was correlation between the amount of Librium used in the initial period of detoxification and the initial blood alcohol concentration. PMID- 4026963 TI - Analysis and subcellular localization of lipid in alcoholic liver disease. AB - The nature and subcellular distribution of lipids in alcoholic liver disease have been little studied. Micro-methods for lipid analysis were applied to needle biopsy homogenates and their subcellular fractions. Alcoholic fatty liver was accompanied by a major increase (up to 50 fold) in triglyceride and a smaller (2 3 fold) increase in cholesteryl ester: there was no significant change in the free cholesterol, free fatty acid or phospholipid content. Homogenates were fractionated into macro- and micro-droplets and membrane fractions by differential centrifugation. The subcellular location of the membrane lipids were determined by sucrose density gradient centrifugation in a vertical pocket reorientating rotor. In fatty liver, although there was a 2-3 fold increase in macro-droplet and micro-droplet (tentatively identified as VLDL) lipid, the major increase was in the membrane-bound triglyceride (8-10 fold). Sucrose density gradient centrifugation demonstrated that these membranes had an equilibrium density of 1.12 g/ml, clearly separated from droplet lipid, density less than 1.04 g/ml. The membrane fraction was tentatively identified as Golgi in origin and it is suggested that alcoholic fatty liver in man is due to impaired Golgi secretion of triglyceride-rich lipid complexes. PMID- 4026964 TI - Hepatic hemodynamics in alcoholic liver injuries assessed by reflectance spectrophotometry. AB - We have investigated the hepatic hemodynamics by reflectance spectrophotometry in patients with alcoholic liver disease. The analysis of 32 cases has shown that the estimated regional hepatic tissue blood hemoglobin concentration, expressed as a difference in absorbance between 569 and 650 nm (delta Er569-650), decreased significantly with progress of fibrosis in the liver, suggesting the relative compression of the vascular compartment due to the progress of alcoholic liver disease. The estimated hepatic oxygen consumption also decreased with progress of fibrosis in the liver. The estimated hepatic oxygen consumption correlated positively with prothrombin time and serum albumin level, and negatively with the fifteen minute retention rate of indocyanine green. Thus, it is concluded that the imbalance between supply and utilization of oxygen in the liver may have an important role in the progress of alcoholic liver disease. PMID- 4026965 TI - Effect of ethanol and iron on the hepatic and biliary levels of glutathione and lipid peroxidative indexes. AB - Data presented here indicate that iron exposure exacerbates the changes in the glutathione status of the liver cell and the lipid peroxidative response of the tissue induced by acute ethanol intoxication. In these conditions, additivity in lipid peroxidation was found to occur either when the process was estimated by hepatic malondialdehyde formation, as well as by measurements of the biliary malondialdehyde release in the anesthetized rat and by the antioxidant-sensitive respiration in the perfused rat liver, procedures which are non-invasive for the tissue. PMID- 4026966 TI - Effect of alcohol ingestion on portal venous blood flow in healthy volunteers: comparison between the subjects with and without ALDH I isozyme. AB - Effect of alcohol ingestion (25 g ethanol) on portal venous blood flow was investigated in healthy subjects using an ultrasonic pulsed doppler method. It was found that; (1) portal blood flow increased by 24% at 30 minutes and returned to the basal level at 60 minutes after alcohol ingestion; (2) there was no significant difference in the effect of alcohol ingestion on portal blood flow between the subjects with and without ALDH I isozyme; (3) blood ethanol levels correlated with portal blood flow at 30 minutes after alcohol ingestion, while this correlation was not observed at 60 minutes thereafter; and (4) blood acetaldehyde levels did not correlate with portal blood flow either at 30 minutes or at 60 minutes following alcohol ingestion. In conclusion, the portal blood flow increases following alcohol ingestion which is not associated with the increase in the blood acetaldehyde level. PMID- 4026967 TI - Chemiluminescence and superoxide dismutase in the plasma in patients with alcoholic and non-alcoholic liver injuries. AB - The chemiluminescence level and superoxide dismutase (SOD) activity were determined in the plasma of patients with alcoholic and non-alcoholic liver injuries. Chemiluminescence level was significantly higher in alcoholics than in non-alcoholics. It increased significantly in patients with fatty livers and had a tendency to increase with the progression of alcoholic liver injury from a fatty liver to liver cirrhosis. Mn-SOD activity was elevated in patients with alcoholic liver injuries. Furthermore, there was a positive correlation between the levels of plasma chemiluminescence and plasma Mn-SOD activity. The increases in chemiluminescence and Mn-SOD activity suggests that the generation of a large amount of activated oxygen is associated with the pathogenesis and progression of alcoholic liver injury in humans. PMID- 4026968 TI - Acute ethanol ingestion by humans and subacute treatment of rats increase urinary folate excretion. AB - Previous studies with rats showed that acute treatment with ethanol (4 g/kg) produce a marked increase in urinary folate levels, followed by a decrease in plasma folate levels. Analogous studies with human volunteer subjects using a lower dose of ethanol showed that there were small, but statistically significant increases in urinary folate levels after four hours. The initial ethanol dose was 1.0 g/kg with a single supplement of 0.1-0.2 g/kg to maintain ethanol blood levels at about 100 mg/dl for six hours. Further studies with rats were designed to test the cumulative effects of repeated daily doses of ethanol. Male Sprague Dawley rats were treated for 1, 2, 3, or 4 days either with ethanol orally in 4 doses of 1 g/kg each at 0, 1, 2, and 3 hours or with glucose orally in 4 isocaloric doses. Urine was collected at timed intervals up to 12 hours after each daily dose. The pattern of the increase in urinary folate levels was similar in all groups, whether treated for 1, 2, 3 or 4 days. These results suggest that repeated ethanol treatment can lead to a marked cumulative folate loss via increased urinary excretion and that increased urinary folate excretion may contribute to the development of folate deficiency in humans. PMID- 4026969 TI - Spontaneous recovery from ethanol-induced male infertility. AB - Chronic ethanol ingestion by the male is associated with reproductive impairment. No longitudinal studies have been carried out to determine the recovery of ethanol-related reproductive failure subsequent to moderate periods of abstinence. An animal model (C57B1 mouse) was utilized to examine the effectiveness of abstinence for reversal of ethanol-induced reproductive failure. After treatment with either a 5% ethanol diet (10 weeks) or a 6% ethanol diet (5 weeks), animals were hemicastrated (right testis and accessory organs); their reproductive tracts and epididymal spermatozoa were examined. Ingestion of the 5% and 6% ethanol diets resulted in significantly (p less than 0.05) decreased testicular weights (24% and 28%, respectively) and seminal vesicle/prostate weights (20%, 6% diet only), increased frequencies of germ cell desquamation (480% and 400%), inactive seminiferous tubules (186% and 567%) and inhibition of in vitro fertilization of mouse oocytes by epididymal spermatozoa (26% and 62%), as compared to their respective pair-fed control values. Also observed was a significant decrease in total motile spermatozoa (85%, 6% diet only). Improvement in all parameters was observed in the contralateral reproductive organs subsequent to ten weeks abstinence. Only germ cell desquamation remained significantly elevated (100% as compared to control) in animals that ingested the 5% diet. In contrast, significant abnormalities persisted ten weeks after treatment with the 6% ethanol diet, including increased germ cell desquamation (200%) and inactive seminiferous tubules (157%); decreased forward progression (17%) of epididymal sperm also persisted. If these data can be applied clinically, male alcoholic patients with reproductive disorders could have a prognosis of at least partial recovery following moderate periods of abstinence from ethanol. PMID- 4026970 TI - Contingent tolerance to the anticonvulsant effects of alcohol. AB - Ethanol (1.5 g/kg) administered intraperitoneally to kindled rats blocked the seizures normally elicited in these subjects by electrical stimulation of the amygdala. Tolerance to this anticonvulsant effect developed following a series of ethanol intubations delivered at 48-hr intervals only when an amygdaloid stimulation was administered during each period of ethanol intoxication. Subjects stimulated 1 hr following each intubation were tolerant to the intraperitoneal test dose after only five intubations (2 g/kg), whereas those stimulated 1 hr prior to each intubation displayed no tolerance during the course of 20 such trials. Even at high intubation doses (5 g/kg), significant levels of tolerance to the anticonvulsant effect of the intraperitoneal test dose were not observed in subjects unstimulated during each period of post-intubation intoxication. These findings emphasize the important role of response contingency in ethanol tolerance; tolerance develops readily for only those effects of alcohol that repeatedly manifest themselves during the periods of ethanol exposure. PMID- 4026971 TI - Hyperventilation, anxiety, craving for alcohol: a subacute alcohol withdrawal syndrome. AB - Hyperventilation leading to respiratory alkalosis is part of the acute alcohol withdrawal syndrome On the basis of clinical observations and a literature review on withdrawal symptoms the following was hypothesized: (a) hyperventilation is also part of a subacute alcohol withdrawal syndrome and (b) hyperventilation appears together with anxiety and craving for alcohol. These hypotheses were tested in a sample of 37 male alcoholic inpatients, abstinent for periods from several weeks to 9 months. Subjects were administered a questionnaire dealing with drinking history and craving for alcohol during abstinence, the Spielberger Anxiety Inventory and a hyperventilation complaint checklist. Subjects' disposition to hyperventilation was assessed during a physiological measurement session. Results show that hyperventilatory symptoms, anxiety and craving for alcohol appear together. Moreover, the severity of hyperventilatory and anxiety symptomatology is positively correlated with the duration of physically dependent alcohol use but not with the duration of excessive drinking per se, irrespective of age. These results corroborate the hypotheses outlined before. PMID- 4026972 TI - Individual alcohol reaction profiles. AB - The purpose of this study was to evaluate interindividual variation in acute reactions to ethanol. Six young, healthy female subjects participated in a double blind experiment consisting of two identical alcohol sessions and one control session where glucose was infused instead of ethanol. Alcohol was infused in a standardized way to reach blood alcohol concentration of 1 mg/ml in 1 hr. During the 4 hr-sessions EEG-spectra, smooth pursuit eye movements, various mood variables, BAC and breath alcohol concentrations were studied repeatedly. The results showed that the subjects had a rather repeatable, individual reaction profile as expressed by changes in alpha mean frequency, theta band power, amount of corrective eye movements and subjective intoxication. The sensitivity of the subject to ethanol should thus be expressed as a reaction profile rather than as a change in a single variable. PMID- 4026973 TI - The myth of "the average alcohol response". AB - The human alcohol response literature often states or implies that there is little variation among normal individuals in their responses to a standard dose. To test this assumption, a wide variety of alcohol responses was reviewed in studies where the original, individual responses were available. All such responses showed variability among individuals. Seven alcohol responses (individual changes from pre-alcohol baseline in heart rate, systolic and diastolic blood pressure, automobile driving ability, and three tests for intoxication) in normal males are analyzed in detail. Each response shows marked, significant individual variability. Genetic differences among individuals (in addition to environmental differences) are probably important in producing this variability. Since normal persons can vary greatly in their alcohol responses, it is not only incomplete but misleading to give only the mean value. Information on the range and frequency distribution of responses is also needed. PMID- 4026975 TI - Language processing in men at risk for alcoholism: an event-related potential study. AB - Event-related potentials (ERPs) were recorded from a group of men with (FH+) and without (FH-) a family history of alcoholism. ERPs were recorded over the left and right cerebral hemispheres and over midline locations while subjects performed a letter rhyming task. The ERPs to the letters displayed major group differences in a negative component with a latency of 430 msec (N430). The amplitude of N430 was significantly smaller in the FH+ as compared to the FH- subjects. These group differences were more pronounced in ERPs recorded from over the right than the left hemisphere. In addition, in the FH+ group only the latency of N430 was linearly related to personal drinking habits. These results suggest that (1) certain brain functions associated with the language processing required in this task are different in men at high and low risk for the development of alcoholism and (2) moderate social use of ethanol may have more pronounced effects on language-relevant brain functions in FH+ than in FH- individuals. PMID- 4026974 TI - Drinking style of parents of alcoholic and control probands. AB - One aspect of the familial component of alcoholism is the use of alcohol among the parents of affected individuals. Both the individual and concordant drinking styles of the parents of 291 inpatient alcoholic probands and 71 non-alcoholic control subjects were measured using family history methods. Social drinking was almost twice as prevalent among fathers of controls compared to fathers of alcoholics. Problem drinking was more than twice as prevalent among the fathers of alcoholics compared to fathers of controls. The abstinence rate for fathers of both groups was similar. Mothers' drinking styles were similar to the fathers' pattern for both groups. Concordance of drinking style in the parental pair was examined. Similarity in drinking style for the parents of control probands was greatest for social drinking. For parents of alcoholic probands high concordance was also found by problem drinking. Overall a great similarity in drinking style was found for the parents of control probands compared to the parents of alcoholic probands. PMID- 4026976 TI - The influence of alcohol abuse as a hidden contributor to mortality. AB - Although only about 2-3 percent of annual deaths are attributed to one of the four underlying causes linked to chronic alcohol use, research results suggest that the impact of alcohol is much greater. The recent issue of mortality multiple cause of death tapes from National Center for Health Statistics permit exploration of associations of chronic alcohol abuse with conditions coded as underlying cause of death and provide leads for case-finding. Data analysis is reported from certificates of resident deaths in the United States in 1978. There are 12 groups of underlying causes for which the percentage of pairings with chronic alcohol abuse ranges from 4-16 percent of the number of deaths from the underlying cause. Age, sex, and metropolitan status of residence are associated with a listing of chronic alcohol abuse among decedents of liver cancer, varicose veins, symptomatic heart disease, septicemia, and respiratory system disease. Planners concerned with secondary prevention can use these clues provided by logistic regression modelling as an aid in case-finding. PMID- 4026977 TI - Impact of changes in distilled spirits availability on alcohol distribution. AB - An important change in the distribution and availability of distilled spirits in North Carolina has resulted from a move to liquor-by-the-drink. Previously drinkers had to plan to bring distilled spirits with them to eating establishments and purchase mixers and ice; LBD eliminates the need for such planning and makes liquor more easily available. The shift from more restrictive to less restrictive availability does not occur immediately after a local election but is gradual over a two-year period following a local election. PMID- 4026979 TI - Treatment of alcoholism and concomitant drugs of abuse. AB - It has been proposed that concomitant substances of abuse may have additive or synergistic properties such that alcoholics using other substances of abuse concurrently may have a harder time giving up alcohol than alcoholics abusing only alcohol. The present study surveyed 291 alcoholics in an alcohol treatment program and 86 social drinker controls matched on age, education, SES and gender. Alcohol consumption, smoking, coffee intake, other substances of abuse. Beck depression and Spielberger Anxiety (State) were measured. Alcoholics drank significantly more alcohol than did social drinkers per day (350.19 cc versus 28.08 cc, p less than 0.001), consumed more caffeine/day (486.3 mg versus 339.9 mg, p less than 0.002), smoked more cigarettes/day (27.8 versus 12.8, p less than 0.001), were more depressed (16.8 versus 4.4 (Beck), p less than 0.0001), had lower internal locus of control scores (37.6 versus 39.7, p less than 0.005), had higher scores on control by chance (22.7 versus 20.2, p less than 0.03) and were significantly more anxious (52.5 versus 33.9 on Spielberger's State Inventory p less than 0.0001). Some patients used stimulants, tranquilizers, depressants, narcotics or toluene. Only 3/258 abused alcohol without using other drugs. Results support earlier studies showing strong associations between alcohol and smoking and between alcohol and caffeine consumption. The alcoholic abusing only alcohol is very rare. Treatment programs need to pay attention to concomitant drugs of abuse. PMID- 4026978 TI - Clinical conditions in alcoholics during long-term abstinence: a descriptive, longitudinal treatment study. AB - After inpatient treatment for acute withdrawal during 1-2 weeks, twelve male alcoholics were treated as outpatients and received disulfiram per os. clinical ratings using a scale with 14 items were performed three times a week during six months. After acute withdrawal had ceased, all patients had positive ratings for anxiety, sleeping problems and autonomic disturbances lasting for 4-8 weeks. They also scored for depressive symptoms, concentration difficulties and failing memory during this period. The following 8-12 weeks all patients but one had periods of mood changes with a duration of 1-3 weeks. During periods with low mood changes several other symptoms appeared, while other psychiatric symptoms were absent during periods with elevated mood. All relapses occurred in connection with periods of mood changes. To conclude, this rating scale made it possible to identify a protracted subacute withdrawal phase and phases characterized by changes of mood, depressive-astenic as well as hyperactive, during long-term abstinence. These clinical phases are suggested to be of importance for clinical treatment and research. PMID- 4026980 TI - The perception of problem drinkers by general hospital staff, general practitioners and alcoholic patients. AB - A sample of 275 subjects (general hospital staff, general practitioners and alcoholic patients) was investigated regarding their perception of problem drinkers. A set of semantic differential scales was used, and subjects were asked to evaluate the concepts of "problem drinker," "self" and "ideal self." Psychological distance was measured in terms of bipolar personality constructs between each of the above concepts. Significant differences were found between the groups in terms of concept evaluation and psychological distance. The implications of these findings for both research and treatment are discussed. PMID- 4026981 TI - The effects of neurohypophyseal hormones on tolerance to the hypothermic effect of ethanol. AB - Mice were made tolerant to the hypothermic effect of ethanol by repeated administration of ethanol (4 g/kg, 25% v/v, IP) on three consecutive days. The colonic temperature was measured in individually-housed animals immediately before and 45 min after ethanol treatment. Peptide treatments with various schedules were made SC 2 hr before the first ethanol challenge. The decrease in hypothermic response was accepted as a tolerance phenomenon, which developed in control animals by day 2. A single injection of oxytocin (OXT) or lysine vasopressin (LVP [0.1 or 1 IU peptide] animal) before the first ethanol injection did not change the initial sensitivity to ethanol. This absence of acute interactions is also reflected in the sleep onset and sleep duration after 5 g/kg ethanol (IP). In contrast, both OXT and LVP affected the development of tolerance. Repeated treatments with graded doses of OXT (0.5-2 IU) or LVP (0.25-1 IU) every day for 3 days blocked the development of tolerance. 0.002 IU LVP facilitated the development of hypothermic tolerance. The remaining doses of the peptides were ineffective. A high dose of LVP (1 IU) facilitated hypothermic tolerance if the peptide was injected when tolerance to ethanol had developed fully without previous peptide treatment. OXT, on the other hand, was ineffective in this particular experimental model. The data suggest that both neurohypophyseal hormones (LVP and OXT) block the early developmental phase of tolerance to ethanol. On the other hand, LVP facilitated the expression of tolerance if the peptide was given to mice with fully developed tolerance. PMID- 4026982 TI - Effects of scopolamine on spontaneous alternation and shuttle avoidance in rats exposed to alcohol in utero. AB - The behavioral effects of the anticholinergic scopolamine were examined in rats exposed to alcohol prenatally. Pregnant Long-Evans rats received isocaloric liquid diets containing either 35% or 0% ethanol-derived calories on Days 6-20 of gestation. A pair-feeding procedure was used, and a lab chow control group was also included. In Experiment 1, adult offspring were tested on a spontaneous alternation task following 1 mg/kg scopolamine or saline. Independent of prenatal treatment, scopolamine caused an increase in the number of trials to alternate. In Experiment 2, offspring were tested on a two-way shuttle avoidance learning task following a 1 mg/kg injection of scopolamine or methylscopolamine. Alcohol exposed animals injected with methylscopolamine made fewer avoidances than controls on the second day of testing while treatment with scopolamine enhanced avoidance performance to control levels. These data suggest that prenatal exposure to alcohol does not interfere with scopolamine-induced changes in the behavior of adult rats. PMID- 4026983 TI - Predicting the onset of compulsive drinking in alcoholics: a biopsychosocial model. AB - An attempt is made to develop a formal quantitative model for predicting the conditions under which compulsive drinking will appear in alcoholics. Biological variables are represented by phenomenological concepts as are psychological and social variables. The usefulness of the model in resolving apparent conflict among concepts and empirical findings is explored. Limitations of the model are examined as are further necessary extensions of it in terms of alcoholic subgroups and multiple biopsychosocial models. PMID- 4026984 TI - Effects of ethanol on eye movements in the monkey. AB - Ethanol (0.25-2.0 g/kg) was administered by remotely controlled intravenous infusion to monkeys engaged in performance of a short-term memory task which required attention to and retention of visual stimuli. Eye movements were monitored and measured by recording the electrooculogram with implanted periorbital Ag/AgCl electrodes. Ethanol induced the following dose-dependent changes of ocular motility: (a) diminution of the frequency of saccades; (b) prolongation of fixation (immobility) periods, though stimulus-elicited fixations became shorter; (c) increase in saccade excursion; (d) increase in saccade duration; and (e) decrease in saccade velocity (preceded at low doses by a transient increase). These changes were correlated with an impairment of behavioral performance. The results of eye movement analysis complement the results obtained on studies of human subjects by oral administration of ethanol. The findings of the present study in the nonhuman primate are interpreted as a reflection of the deleterious effects of alcohol on the cerebral substrate of visual attention. PMID- 4026985 TI - Organization of the commissural projection to the dentate gyrus is unaltered by heavy ethanol exposure during gestation. AB - The anterograde horseradish peroxidase method was used to determine if prenatal exposure to ethanol affected the development of the characteristic afferent lamination pattern of the commissural projection to the dentate gyrus. Mean ethanol consumption for the ethanol-consuming dams was 12.7 g/kg +/- 0.3 g per day. Adult offspring of rats that consumed a liquid diet containing 35% ethanol derived calories during days 1-21 of gestation, and both pair-fed and normal controls were examined. Brain weights and volumes of the ethanol and pair-fed control rats did not differ significantly from normal controls. However, body weights of ethanol-exposed rats were significantly reduced compared to normal controls. Computer-assisted image analysis of the HRP-labeling revealed that in spite of the heavy ethanol exposure there was no evidence of alterations in the spatial distribution of the commissural terminal field. PMID- 4026986 TI - Elevated blood acetate as indicator of fast ethanol elimination in chronic alcoholics. AB - The concentration of acetate was determined in the hepatic and peripheral blood of 10 chronic alcoholics and six healthy non-alcoholic controls after a peroral dose of ethanol (0.8 g/kg b.wt.). The blood acetate concentration was significantly higher in the hepatic vein than peripherally and remained at a rather constant level both in alcoholics and controls during the course of ethanol elimination. However, the level of acetate was significantly (p less than 0.005) higher in alcoholics than in controls both in the hepatic vein (1.79 and 1.15 mM) and peripherally (0.91 and 0.52 mM) (alcoholics and controls respectively). The alcoholics also eliminated ethanol 54% faster than the controls (159 mg/kg b.wt./hr and 103 mg/kg b.wt./hr; alcoholics and controls respectively). Furthermore a highly significant correlation was found between the rate of ethanol elimination and blood acetate level both in the hepatic (r = 0.877, p less than 0.001) and in the peripheral vein (r = 0.799, p less than 0.001). Our results suggest that an increased level of blood acetate during ethanol oxidation may be used as an indicator of enhanced ethanol elimination. PMID- 4026987 TI - Cyanamide injections during alcohol deprivation increase alcohol drinking. AB - Long-Evans male rats were given 7 weeks of choice between 10% ethanol and water and then were divided into 6 matched groups, 3 of which were then deprived of alcohol for 6 days. Subcutaneous cyanamide injections (10 mg/kg, 3 times daily, for 4 days) during alcohol deprivation produced a long lasting, significant increase in subsequent alcohol selection, over and above the increase produced by alcohol deprivation alone. The same injections given to a group not deprived of alcohol caused a significant suppression of alcohol drinking during the treatment and had disappeared 4 days after the last injection. Thereafter the drinking remained at the control level and did not rise to that of the group given the injections during deprivation. The groups did not differ in their subsequent selection of saline solutions. PMID- 4026988 TI - Reversible helix/coil transitions of left-handed Z-DNA structures. Comparison of the thermodynamic properties of poly(dG).poly(dC), poly[d(G-C)].poly[d(G-C)], and poly(dG-m5dC).poly(dG-m5dC). AB - In contrast to poly(dG).poly(dC), which remains in the B-DNA conformation under all experimental conditions the polynucleotides with the strictly alternating guanine/cytosine or guanine/5'-methylcytosine sequences can change from the classical right-handed B-DNA structure to the left-handed Z-DNA structure when certain experimental conditions such as ionic strength or solvent composition are fulfilled. Up to now the investigation of the helix/coil transition of left handed DNA structures was not possible because the transition temperature exceeds 98 degrees C. By applying moderate external pressure to the surface of the aqueous polymer solution in the sample cell the boiling point of the solvent water is shifted up the temperature scale without shifting the transition temperature, so that we can measure the helix/coil transition of the polynucleotides at all experimental conditions applied. It can thus be shown that the Z-DNA/coil transition is cooperative and reversible. The Tm is 125 degrees C for poly(dG-m5dC).poly(dG-m5dC) in 2mM Mg2+, 50mM Na+, pH 7.2 and 115 degrees c for poly[d(G-C)].poly[d(G-C)] in 3.04M Na+. The transition enthalpy per base pair was determined by the help of an adiabatic scanning microcalorimeter. PMID- 4026989 TI - Metabolic phosphorylation and excretion of some nucleoside analogues in insects. AB - After oral administration to the hemipteran insect Pyrrhocoris apterus L. (Fireburg), the L-enantiomers and certain open-chain analogues of the nucleosides are rapidly converted into the corresponding monophosphates, which are then excreted. This metabolic phosphorylation is almost quantitative; it occurs at the primary as well as at the secondary hydroxylic groups. The process is abolished when the respective nucleoside analogues contain a free carboxylic group. By contrast, the phosphorylating capacity is unaffected by structural variations at the heterocyclic base. This phosphorylation and excretion may represent a part of detoxication mechanism for the above nucleoside analogues. PMID- 4026990 TI - Nonenzymatic glycation of immunoglobulins leads to an impairment of immunoreactivity. AB - Incubation of purified human and rabbit immunoglobulin G with glucose leads to covalent incorporation of the sugar into the protein, depending on glucose concentration, incubation time and pH. Furthermore, the level of glycated immunoglobulin G from normal and diabetic subjects has been determined using the thiobarbituric acid reaction. The median for glycated immunoglobulin G, expressed as mmol 5-hydroxymethylfurfural per mol IgG, obtained from 20 normal and 29 diabetic subjects was 62 and 107, respectively. Glucose incubation of immunoglobulin G purified from rabbit anti-human-transferrin serum, from human anti-varicella/zoster virus serum and from human anti-lues-spirochete serum, respectively, leads to a marked decrease in biological activity, as determined in a micro complement fixation test. Inactivation of specific antibody was dependent on incubation time and glucose concentration employed. Loss in complement-fixing activity was observed at glycation levels well comparable to those found in diabetics. PMID- 4026991 TI - The lectin-binding protein from the pea (Pisum sativum); properties and interactions. AB - The lectin-binding protein (lectin binder) from the garden pea (Pisum sativum) was studied. It is a glycoprotein composed of four subunits of about 50 000 Da. Its amino-acid composition and molecular mass differ from those of lectin and of storage proteins. The interaction between lectin and lectin binder is demonstrated and quantified by several different methods and is shown to be specifically sugar-dependent. A biological function of lectin binders and lectins is discussed. PMID- 4026992 TI - The complete covalent structure of hirudin. Localization of the disulfide bonds. AB - Hirudin, the thrombin-specific inhibitor from the leech Hirudo medicinalis, is a single-chain polypeptide (65 amino-acid residues) linked by three disulfide bridges. Localization of the three disulfide bonds could be assigned on the basis of the structures of cystine peptides derived by high performance liquid chromatography separations of thermolysinolytic digest of native hirudin. By characterization of the nine major fragments by amino-acid analysis, N-terminal amino-acid determination and sequence analysis, the following disulfide linkages were identified: Cys6-Cys14, Cys16-Cys28 and Cys22-Cys39. Due to the lack of any closer sequence homology and topological structural homology to other serine proteinase inhibitor proteins, hirudin seems to be unique in its primary structure and hence designates an unknown inhibitor family. PMID- 4026994 TI - Hemocyanins in spiders, XX. Sulfhydryl groups and disulfide bridges in subunit d of Eurypelma californicum hemocyanin. AB - Subunit d of Eurypelma californicum hemocyanin contains after reduction 7 cysteine residues. Using 3,3'-dithiobis(6-nitrobenzoic acid) 3 mol cysteine/mol subunit were determined. The cysteine- and cystine-containing peptides of subunit d were obtained by cyanogen bromide cleavage and subsequent treatment with trypsin. The free cysteines were established at positions 102, 261, and 454 respectively. Cys205-Cys210 and Cys529-Cys579 are connected by disulfide bridges. PMID- 4026993 TI - Primary structure of the hemoglobins from the greater Kudu antelope (Tragelaphus strepsiceros). AB - The adult greater Kudu antelope has two hemoglobin components, Hb A and Hb B, with one alpha and two beta chains. The complete amino-acid sequences of these three chains are presented. The two beta chains differ only in one residue at position 16 (Gly----Ser) and may be the product of two allelic genes. The primary structure of the chains was determined by sequencing the tryptic peptides after their isolation from the tryptic digest of the chains by high performance liquid chromatography. The alignment of these peptides was deduced from homology with the chains of bovine hemoglobin. Between the Kudu hemoglobins and those of cattle a high degree of homology was found. PMID- 4026995 TI - Identification and measurement of acid (specific) histidine decarboxylase activity in rabbit gastric mucosa: ending an old controversy? AB - One of the main obstacles in assigning any distinct function to histamine in health and disease was the longlasting controversy on the existence of any physiological, endogenous histamine formation in man and most of the other mammals except the rat. Using a modification of Schayer's isotope dilution method, a renewed attempt was made to identify the very low activities of an acid (specific) histidine decarboxylase in rabbit gastric mucosa capable of producing endogenous histamine in physiological conditions, to develop tests for its identification in crude enzyme extracts and to demonstrate the specificity of the enzymatic assay by excluding any relevant Dopa decarboxylase activity and also nonenzymatic decarboxylation interfering with the determination of acid (specific) histidine decarboxylase. To achieve this aim five tests were developed: In the pH profile (test 1), a pH optimum was found at 7.0 in the presence of a low substrate concentration (1.6 X 10(-6)M L-[ring-2-14C] histidine). The apparent Michaelis concentration at the pH optimum (test 2) was 1.8 X 10(-4)M, the maximum rate 12.5pmol [14C]histamine formed X min-1. To increase the specificity of inhibition experiments with alpha-methylhistidine and alpha-methyl-L-Dopa a pH profile was determined in the presence of these two enzymatic inhibitors (test 3 and 4). alpha-Methylhistidine was used for a reliable diagnostic confirmation test, alpha-methyl-L-Dopa for a reliable exclusion test. Benzene showed no influence on either blanks or recovery rates, but inhibited the enzymic activity at pH 7.0, not however that of unspecific histidine decarboxylase and hence was very valuable as an additional diagnostic exclusion test (test 5). Although these new tests identifying acid (specific) histidine decarboxylase and demonstrating the specificity of its determination were tedious, despite the use of the modified isotope dilution method, they excluded the presence of any Dopa decarboxylase activity in mixtures with crude enzyme preparations as well as of any kind of nonspecific and nonenzymatic histidine decarboxylation. An endogenous histidine decarboxylase in rabbit gastric mucosa is postulated, capable of forming histamine in vivo. PMID- 4026996 TI - The primary structure of porcine Cu-Zn superoxide dismutase. Evidence for allotypes of superoxide dismutase in pigs. AB - Cu-Zn superoxide dismutase was purified to homogeneity from mixed pig blood and from a single pig. The isolated product had an absorption ratio 280/260 nm of 0.91, a specific activity of 3 000 +/- 200 units (cytochrome c reduction test), and an isoelectric point of 7.5 (chromatofocusing) or 7.25 (isoelectric focusing), respectively. Sequence determination was performed by automated solid phase Edman degradation of fragments of the reduced S-carboxymethylated proteins obtained by digestion with trypsin or Staphylococcus aureus proteinase V8 or treatment with cyanogen bromide. Acetylation of the N-terminus was confirmed by comparing high performance liquid chromatography retention times of N-terminal peptides with those of authentic samples. Sequencing of the superoxide dismutase of mixed porcine blood revealed heterogeneity (70% Leu; 30% Val at position 29), whereas the sample derived from a single French pig proved to be homogeneous (100% Leu at position 29). The complete sequence of pig superoxide dismutase comprised 152 amino-acid residues, which corresponds to a theoretical molecular mass of 15 800 Da per subunit, and exhibited the expected high homology with those of other mammals. The aspartate and all 7 histidine residues known to complex the metal ions in bovine superoxide dismutase are conserved in the porcine sequence at the homologous positions Asp82 and His45, His47, His62, His70, His79, His119, respectively. PMID- 4026997 TI - Alkylation-induced mono(ADP-ribosyl)-histones H1 and H2B. Hydroxylamine-resistant linkage in hepatoma cells. AB - Treatment of hepatoma AH 7974 cells with dimethyl sulfate led to a marked accumulation in vivo of mono)ADP-ribosyl)-histone H1A, H1B, H1 and H2B, respectively. In these conjugates, most of the modifying groups were linked to the acceptor proteins by an 'unusual' bond not described so far for ADP-ribosyl histone conjugates. It resisted treatment with 3M hydroxylamine, 0.1M picrylsulfonate and mild alkali, which excluded a linkage through carboxyl or guanidino residues. The stability of these conjugates formed endogenously differed also from 'non-enzymic' histone H1 conjugates formed by incubation of free ADP-ribose with the histone. Histone-linked mono(ADP-ribosyl) residues synthesized in hepatoma cells in response to alkylation were located exclusively in the domains that interact with DNA, i.e. in the non-globular C-terminal tail of histone H1 and in the N-terminus of histone H2B. Besides poly(ADP ribosyl)ation, the modification of histones by single ADP-ribose groups may represent an independent process to modulate DNA/histone interaction. PMID- 4026998 TI - Ligand binding and stabilization of malate- and lactate dehydrogenase. AB - Binding of coenzymes, coenzyme fragments and phenolate ligands to malate- and lactate dehydrogenase was studied. From linear competition in titration experiments, the coenzyme binding site was concluded to bind all the ligands employed. The analogy between the phenolate ligands and tetraiodofluorescein which is known to bind at the adenosine binding site suggests binding of phenolates at this site. Coenzymes and coenzyme fragments retard the irreversible thermal inactivation of the enzymes. The retardation effect decreases in the order NADH greater than NAD greater than ADPR greater than or equal to AMP for both enzymes. Phenolate ligands binding to the adenosine pocket do not stabilize the enzymes. The stabilization is concluded to originate from the interaction of coenzyme phosphate and nicotinamide with the enzymes. The interactions with the adenosine moiety and with the second ribose seem to be ineffective in retardation of thermal denaturation. PMID- 4026999 TI - Structural studies on the core oligosaccharide of Phenylobacterium immobile strain K2 lipopolysaccharide. Chemical synthesis of 3-hydroxy-5c-dodecenoic acid. AB - The fatty acid composition of the bound lipids of 17 strains from Phenylobacterium immobile was investigated. Ester-linked 3-hydroxy-5c-dodecenoic acid was found to be the major substituent in the lipopolysaccharide. Therefore the occurrence of this unusual acid can be taken as a useful marker for the determination of P. immobile by simple fatty acid analysis. Lipid A backbone was found to consist of 2,3-diamino-2,3-dideoxy-D-glucose, which up to this time has only been detected in group I of purple nonsulfur bacteria and their non phototrophic relatives. A convenient chemical synthesis for 3-hydroxy-5c dodecenoic acid is described. The polysaccharide region of P. immobile strain K2 lipopolysaccharide was investigated. The methods used included gel filtration procedures, methylation analysis, periodate oxidation, Smith degradation, oxidation with chromium trioxide and enzymic degradations of the isolated oligosaccharide. We found that strain K2 has a rough-type lipopolysaccharide, devoid of an O-specific side chain. For the core oligosaccharide the following structure is proposed: (Formula: see text) beta-D-Glcp(1-3)-L-alpha-D-Hep rho(1 3)-L-alpha-D-Hep rho(1-3-L-alpha-D-Hep rho(1-4/5)dOclA. PMID- 4027000 TI - The primary structure of the hemoglobin of the dogfish shark (Squalus acanthias). Antagonistic effects of ATP and urea on oxygen affinity of an elasmobranch hemoglobin. AB - The amino-acid sequence of the hemoglobin of the Dogfish Shark (Squalus acanthias) is presented. The alpha-chains consist of 141 residues and show a Thr/Ser ambiguity at position 3. The beta-chains consist of 142 residues and evidently have no D-helix; they show an Asn/Tyr ambiguity at position 104. Both chains have free N-terminal amino acids. The phylogenetic distance from the human alpha- and beta-chains is indicated by 49.3% and 56.2% amino-acid exchanges. The primary structure is discussed in relation to the oxygen-binding properties of elasmobranch hemoglobin, particularly as regards the antagonistic effects of urea and ATP, and the effects of proton concentration (the alkaline and acid Bohr effects, and the Root effect). PMID- 4027001 TI - [Guiding principles for work in traffic safety with respect to alcohol and driving]. PMID- 4027002 TI - [Accuracy of the forensic determination of blood alcohol]. PMID- 4027003 TI - [Calculation of maximal blood alcohol concentrations and its value as evidence for the assessment of responsibility]. PMID- 4027004 TI - [Status of knowledge about the "0.8 pars pro mille Law." Results of a survey]. PMID- 4027005 TI - [Post-schooling for alcohol offenders in first and repeated cases (attempt at status determination)]. PMID- 4027006 TI - [Post-schooling: a communication problem between judges and psychologists]. PMID- 4027007 TI - [Metabolism and rate of excretion of the congeners propanol-l and isobutanol following the consumption of the "Chivas Regal" brand whiskey]. PMID- 4027008 TI - [Concentration of the congeners propanol-1 and isobutanol in blood following consumption of "Captain Morgan" overseas rum]. PMID- 4027009 TI - [Alcohol and drug crimes from the viewpoint of recent developments]. PMID- 4027010 TI - [Alcoholic intoxication crimes from the foreign viewpoint]. PMID- 4027011 TI - [2 serogenetic blood alcohol identification tests with unusual results]. PMID- 4027012 TI - [Drunk driving in th Bavarian Untermain region]. PMID- 4027013 TI - [Negligent carelessness in Paragraph 315 of the German criminal code and the loss the driver's licence]. PMID- 4027014 TI - [The course of blood alcohol curves after the ingestion of beer and brandy together with "alcohol-free" beer]. PMID- 4027015 TI - [Analysis of cogeners of alcoholic beverages. 1. The application of a capillary gas chromatography micromethod in headspace analysis]. PMID- 4027016 TI - [Incidence of Pseudomonas sp., Staphylococcus sp. and Candida sp. in a high-risk population]. AB - Since infections represent one of the greatest complications in immunocompromised hosts, our group, concerned with bacteriological monitoring, has applied its attention to microorganisms such as Pseudomonas sp, Staphylococcus sp and Candida sp. Pseudomonas sp strains have been identified using conventional techniques and the API system 20 NE. According to Varaldo's scheme, Staphylococci sp have been divided into six "lyogroup" and then, the typing of Candida sp has been checked by cultural and biochemical tests. The results obtained have demonstrated that the Pseudomonas aeruginosa species is prevalent not only in the urinary tract but also in the respiratory tract. As for the Staphylococci sp, the VI lyogroup showed the greatest percentage of strains and than, as regards Candida sp it has been possible to observe that, over a given period, the percentage of pluricontamination has been almost constant. PMID- 4027017 TI - [Production of coagulase and thermonuclease in 366 strains of staphylococci belonging to different lyogroups]. AB - 366 human staphylococci were tested for the production of coagulase and thermonuclease and were subdivided into lyogroups. 98% of the isolates showed uniformly positive or uniformly negative results for the production of two enzymes. All uniformly positive strains belonged to the species Staphylococcus aureus, whereas coagulase-thermonuclease negative strains were easily subdivided into five lyogroups. Seven strains produced only one of two enzymes and were identified by analysis of their bacteriolytic activity. Two of these strains were identified as Staphylococcus aureus, one was coagulase negative and the other thermonuclease negative. PMID- 4027018 TI - Toxoplasma gondii: in vivo and in vitro immunological and ultrastructural patterns of a human low virulent strain. AB - The AA. analyze the ultrastructural and immunological patterns of a low virulent strain of T. gondii cultured in vitro on A-9 cells line (PV-H1C-83). The tissue culture method described here is highly recommended to study the immunological aspects of experimental toxoplasmosis. Biological tests' results and the time courses of serological tests are also similar to those obtained from mice infected with cerebral tissue containing cysts. The low virulent strain (PV-H1C 83), when cultured in vitro, is able to induce the formation of large parasitophorous vacuoles, in which the EM investigation shows a typical cyst wall enveloping numerous bradyzoites. PMID- 4027019 TI - [Evaluation of the immune function of patients undergoing radiotherapy: results after 18 months]. AB - The effects of radiotherapy on subset lymphocyte populations of 15 neoplastic patients were studied. The initial impairment of lymphocyte functions, was restored after eighteen months to 78% of initial values. The numerical equilibrium of T and B subpopulations was completely reinstated. PMID- 4027020 TI - Defect of leukocyte functions and circulating immune complexes in visceral leishmaniasis. AB - Seven patients affected with visceral leishmaniasis have been tested for polymorphonuclear leukocyte functions and for presence of circulating immune complexes during the course of the disease and on recovery. These parameters have been correlated with clinical features; phagocytic and killing defects observed during acute stages of the disease seem to be dependent from high levels of circulating immune complexes observed in same period. Reduction of CIC levels observed after a first course of therapy are probably related to the gradual improvement of phagocytic functions which are almost complete in all patients at recovery. PMID- 4027022 TI - Validation of utilization of glass vials for preparing of lyophilized drugs. PMID- 4027021 TI - [Esculin hydrolysis, a confirmation test for fecal streptococci detected on Slanetz-Bartley medium]. AB - Samples of marine waters have been analyzed for recovering faecal streptococci applying the membrane filtration technique on Slanatez-Bartley medium. It has been pointed out that this medium can yield high proportions of non-group D streptococci: in fact its selectivity seems to be rather low at least for certain samples. This study aims to test and to overcome the disadvantage of the high counts of faecal streptococci due to background microrganisms. The hydrolysis of esculin may be used as a confirmatory test for increasing the selectivity. Membranes showing high numbers of streptococci-like colonies have been transferred from Slanetz-Bartley (MEA) medium to an esculin iron agar (EIA) plate. After 20 min at 41 degrees C small black spots appeared on the backside of the membrane where the colonies had hydrolyzed esculin were resident. The number of positive colonies may be recorded as the real number of faecal streptococci. PMID- 4027023 TI - [Pharmacokinetic behavior of long-acting terramycin in rabbits]. PMID- 4027024 TI - Gastrin release after endoluminal perfusion with cisapride of the isolated antrum in the pig. PMID- 4027025 TI - Stability of ursodeoxycholic acid 7-oleyl ester to enzymatic hydrolysis. PMID- 4027026 TI - [Intraserosal proximal hemideferentectomy versus classical proximal hemivasectomy in the rat. Anatomo-functional aspects and proposal for a new terminology]. AB - According to new trends and terms in microsurgery, the intra-serous proximal hemideferentectomy is compared to the classical vasectomy in rat. The effects of these surgical models are evaluated on morphological and functional bases. The anatomo-pathological parameters considered (stenosis and leakage of the anastomosis of the epididymal tubule conseguent on local ischemia) have been correlated with functional parameters "in vitro" (spontaneous motility and field stimulation) in order to plan the best microsurgical procedure in the experimental tubulo-vasostomy. PMID- 4027027 TI - [Effects of tubulo-deferens stenosis secondary to intraserosal proximal hemideferentectomy and end-to-end tubulo-vasostomy on the testicle of the rat. Histopathological aspects]. AB - The histopathological aspects of the testis in rat after intra-serous proximal hemideferentectomy and end-to-end tubulo-vasostomy are evaluated. The histomorphometric variations of the convoluted seminiferous tubules and the quantitative modifications of the stages of spermatogenesis are correlated with the obstruction's degree of the tubulo-deferential anastomosis. PMID- 4027028 TI - [Simultaneous registration of rheographic and manometric parameters of the inferior esophageal sphincter in the cat]. AB - The aim of the present study was to detect simultaneously hemodynamic parietal events and intraluminal pressure of the Lower Esophageal Sphincter (LES), with particular regards to cyclic changes due to systo-diastolic cardiac activity. A probe for combined Intraluminal Manometric Plethysmography (IMP) and Intraluminal Impedence Plethysmography (IIP) was used. It was a Swan Ganz bipolar pacing catheter, modified by removing the latex balloon from the tip. The exposed side hole (diameter smaller than 0.5 mm) was utilized as a terminal orifice for an infused manometry system. It was preliminarly essayed in bench tests. A perfusion rate of 1.75 ml/min was chosen as it did not induce significant elevations of the pressure base-line and allowed detection of pressure rise rates up to 300 mm Hg/s. The two metallic rings, originally designed for intracardiac stimulation, were used as low resistance electrodes to record impedence variations. Since very small shifts of recording electrodes induce important artifacts, the present experiments were carried out on curarized cats. In these conditions, artificial ventilation could be temporarily stopped to avoid any artifact due to respiration mechanics. The proposed method seems to be satisfactory enough for simultaneous acquisition of IIP and IMP data at LES level. Recordings of IIP allow to reveal changes in parietal blood content which could chiefly be referred to lamina propria and submucosa districts. On the other hand, IMP cyclic fluctuations would signal variations of total sphincteric tension, likely depending on hemodynamic events in all vascular beds of the wall. In our opinion, a more extensive analysis of IMP and IIP waves, as well as of reciprocal relationships between rheografic and manometric parameters, may provide very useful knowledges on sphincteric physiology. PMID- 4027029 TI - [Physiology of interdigestive motor activity in man]. AB - Aim of this work has been to investigate the pattern of interdigestive motility from the esophagus to the duodenum. Six human subjects have been studied by means of a manometric probe. The results are very similar to those described elsewhere, and show that a cyclic motor activity spreads down from the esophagus to the duodenum and that a district control of gastrointestinal motility exists. PMID- 4027030 TI - [Salivary levels of immunoglobulin and dental caries in children]. AB - IgG, IgA, IgM and lysozyme levels were determined in whole unstimulated saliva from ten children aged seven-nine years. IgA levels were significantly higher (p less than 0.05) in caries-susceptible subjects when compared with the caries-free ones. High levels of IgG seemed to correlate with a high DMF score. No correlation was found between lysozyme levels and DMF score. PMID- 4027031 TI - [Activity of uremic toxins and polyamines on organ culture of 7-day-old chick embryo]. AB - We studied possible effects of uremic toxins and polyamines (PAs) on organ cultures of chick embryo. We added on culture media the lyophilized of total dialysate and its chromatographic peak II obtained with chromatography with Sephadex G 15. The total dialysate and peak II showed toxicity with degeneration of the culture, whereas the free PAs, we added, did not effects. PMID- 4027032 TI - [Afferents from a single muscle of the forelimbs and fastigial neurons of the cerebellum]. AB - Responses of neurons in the medial nucleus of cerebellum (CBM) were studied on stimulation of ipsilateral and contralateral homonymous muscles, in decerebrated cats. The aim was to find out to what extent information from homonymous muscles of the forelimbs converge on the same CBM neurons and whether the probability of such a convergence depends on location (axial, proximal, distal) or function (flexor, extensor) of the tested muscles. The analysis was limited to the neurons belonging to the rostral part of the nucleus which is known to control the ipsilateral muscle periphery. Neuronal activity was recorded extracellularly using tungsten microelectrodes (5-12 M omega) and muscle stimulation was performed by bipolar coated steel electrodes, with the exception of the tip. At least 6 pairs of homonymous muscles were generally stimulated: two axial, two proximal and two distal in both forelimbs. Care was taken that, when a muscle was stimulated, the others were not activated either directly or in a reflex way. Out of the 65 neurons studied, 60 (92%) were responsive to muscle stimulation. It was specifically observed that a high percentage of cells reacted to stimulation of distal muscles (74% to ipsilateral and 71% to contralateral ones). More than half (55%) of the neurons were responsive to activation of a pair of homonymous distal muscles and about one third of them (31%) to both the pairs of distal muscles. On the contrary the percentage of responses to proximal muscles was reduced foremost in the ipsilateral ones (23%) and only an exiquous percentage of cells (15%) received information from the homonymous proximal muscles.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4027033 TI - [Analysis of electroneurographic data on a sample of normal subjects]. AB - The ENGraphic basic data of 41 normal subjects were measured to determine a range of normal values and to analyze the importance of individual factors (gender, age, work). The work affects significantly the conduction velocities and the latencies more frequently than gender and age. PMID- 4027034 TI - [Changes in body composition in obese patients on a low-calorie diet]. AB - Energy balance was studied on 4 obese hospitalized subjects kept on hypocaloric diet (489 Kcal - 54% CHO, 10,6% Fat, 35,4% Protein) for 18 +/- 3,7 days. Energy expenditure was measured trough heart-rate monitoring (individual calibrations before and after the study were performed) and nitrogen balance was computed to establish protein loss. Individual qualitative composition of body weight loss was then assessed: 71,4 +/- 5,23% could be attributable to fat loss, 9,38 +/- 3,32% to protein loss, 18,2 +/- 5,5% to water loss. Part of this last figure could be attributable to a slight under-estimation of the method utilized to measure the energy expenditure (heart-rate monitoring). PMID- 4027035 TI - [Interference of polyester inflammation on the development of Yoshida ascites hepatoma in the rat]. AB - Minced polyester threads introduced into the peritoneal cavity cause a chronic inflammation with evidence of macrophage and lymphocyte stimulation. In this paper an interference between this kind of inflammation and the growth of Yoshida ascites hepatoma has been shown, which has been found to dependent on the time interval elapsed between the introduction of polyester (Mersilene) minces and injection of the hepatoma cells. Rats were treated intraperitoneally with Mersilene and then divided in to three groups: the first was injected intraperitoneally with hepatoma cells immediately (TM 0), the second after 7 (TM 7) and the third after 14 days (TM 14); rats untreated with polyester and implanted with the same number of hepatoma cells served as controls (NT). While in groups NT and TM 0 a rapid growth of hepatoma cells occurred, together with the accumulation of a considerable volume of ascitic fluid, no tumor growth neither ascite production occurred in groups TM 7 and TM 14; in these animals where several days were allowed to elapse after polyester introduction, the hepatoma cells which had been injected rapidly disappeared and were no more found 48 h after the intraperitoneal injection. It is suggested that the inhibition of the neoplastic growth may be dependent on the activation of macrophages (and possibly NK cells) which accompanies the development of the chronic polyester inflammation. PMID- 4027036 TI - [Kinetics of cellular adhesion to different materials used in implants]. AB - The authors expose their observations about the kinetics of cell adesion on two materials used as implants in orthopaedic surgery, AISI, 316 L steel and passivated titanium. The kinetics of cell attachment have been compared: an initial rapid increase of bound radioactivity was observed on passivated titanium (in 5 - 30 min) and after this rapid reaction the number of attached cells increased only slowly, during the following 30 min. After incubation of 90 min, almost all cells became attached. Kinetic of BHK cell attachment on AISI 316 L differs significantly: almost all added cells were attached in 90 min but the rapid increase of attachment is observed only during the first 30 min. These observations are important for the comprension of adhesion mechanisms and characterize the properties of biocompatibility of implant materials. PMID- 4027037 TI - [Purification and characterization of ribulose-1,5-diphosphate carboxylase in artichoke leaves. I. Isolation and purification]. PMID- 4027038 TI - [Purification and characterization of ribulose-1,5-diphosphate carboxylase in artichoke leaves. II. Molecular weight and oligomeric structure]. PMID- 4027039 TI - Fatty acid synthesis in brown adipose tissue subcellular fractions of hyperthyroid rats. PMID- 4027040 TI - [Hepatic glutamine-5-phosphoribosyl-1-pyrophosphate amidotransferase and glucocorticoids]. PMID- 4027041 TI - [In vitro culture of mouse embryos]. PMID- 4027042 TI - [Synchronization of ovulation and the collection of embryos in mice]. PMID- 4027043 TI - [Monthly determinations of alkaline phosphatase and heavy metals (zinc, copper) in Venus gallina L]. PMID- 4027044 TI - [Auxin and anti-auxin activity of 3-oxo-1,2-benzoisothiazoline-2-alkanoic acids]. PMID- 4027045 TI - [Antagonism by taurine of hyperthermia induced in rabbits by 6-aminomethyl 4H,1,2,4-benzothiadiazine 1,1-dioxide (AMBD) and by calcium antagonists]. PMID- 4027046 TI - [Biochemical effects of anaerobiosis in Venus gallina L. and Scapharca inaequivalvis (Bruguiere)]. PMID- 4027047 TI - Contribution of peripheral and central mechanisms to the oesophageal primary peristalsis. PMID- 4027048 TI - [Spontaneous activation of regenerated motor axons in the presence of ethanol]. PMID- 4027049 TI - [Recurrent neurons of the superior cervical ganglion of the rat: an electrophysiological study]. PMID- 4027050 TI - [Redistribution of hepatic arterial blood flow after arterial infusion of microspheres of degradable starch in patients with hepatic metastases from colorectal carcinoma]. PMID- 4027051 TI - Music draws attention to the left and speech draws attention to the right. AB - Providing free-field music input prompts right-handers to attend to their left side in a loudness-matching task that requires no musical analysis. Conversely, speech prompts rightward attention. The processes inferred are akin to the attentional asymmetry demonstrated in the syndrome of hemispatial neglect. PMID- 4027052 TI - Hemispheric asymmetry in memory search for four-letter names and human faces. AB - Two memory search experiments were conducted using vertically oriented four letter names and human faces as stimuli. Subjects were required to indicate as quickly and as accurately as possible whether or not a single probe stimulus (presented for 150 msec to either the left or right visual field) was contained in a set of 2, 3, 4, or 5 items being held in short-term memory. The probe stimuli were presented alone (clear condition) or centrally embedded in a matrix of dots (degraded condition). In Experiment 1 (involving names), a right visual field/left hemisphere advantage was obtained and pinpointed at the encoding stage rather than at the memory comparison stage of the information-processing system. For Experiment 2 (involving human faces), no hemispheric advantage was readily observed. In each experiment, both the left hemisphere and the right hemisphere employed an abstract memory comparison operation from which the effects of probe degradation have been removed. These results are discussed in terms of their implications for various models of hemispheric asymmetry. PMID- 4027053 TI - Effects of a concurrent memory task on hemispheric asymmetries in categorization. AB - Recent research on the division of processing between the two cerebral hemispheres has often employed two concurrent tasks to investigate the dynamic nature of hemispheric asymmetries. The experiment reported here explored the effects of two concurrent high-level cognitive tasks (memory retention and semantic categorization) on the direction and magnitude of hemispheric differences in the processing of words and pictures. Subjects were required to categorize words and pictures presented to either the left visual field-right hemisphere (LVF-RH) or the right visual field-left hemisphere (RVF-LH). The categorization could be performed while holding either verbal material in memory (digit span), pictorial material in memory (serial nonsense figure recognition), or with no concurrent memory task. The effects produced hemisphere-specific, material-nonspecific interference. The verbal task removed a RVF-LH advantage at word categorization and enhanced a LVF-RH advantage on picture categorization; the pictorial task interfered with picture categorization in the LVF-RH, while enhancing a RVF-LH advantage at word categorization. The results are discussed in terms of multiple resource models of hemisphere function, capacity limitations, and the functional locus of processing required to produce various dynamic hemispheric effects. PMID- 4027054 TI - The effects of visual feedback on hemispheric alpha asymmetries and reported processing strategies: a single-subject experimental design. AB - A double reversal single-subject experimental design was used to study the effects of visual feedback on the hemispheric alpha asymmetries of a male subject during a linguistic task. Results indicated that the subject demonstrated flexibility in hemispheric alpha and corresponding processing strategies employed when an alpha biofeedback procedure was used. These results provide further support for the notion that right and left hemispheric activation is associated with different, yet compatible, cognitive strategies and that both can be manipulated under conditions of feedback. PMID- 4027055 TI - Anterior-posterior interhemispheric differences in the loci of lesions producing visual hemineglect. AB - Five neuropsychological tests designed to measure the presence and severity of visual hemineglect were given to 101 patients with clearly defined unilateral lesions. Of these, visual hemineglect was present in 28 out of a total of 56 left brain damaged (LBD) patients and in 20 out of 45 right brain damaged (RBD) patients. The incidence of hemineglect in these groups did not differ significantly, but the severity of hemineglect was greater in the RBD group than in the LBD group. However, the two groups were found to differ significantly with respect to the loci of the lesions most likely to result in hemineglect. In the RBD group most patients with hemineglect had posterior lesions, and in the LBD group most patients with hemineglect had anterior lesions. Possible reasons for this were discussed first from the point of view of an inattention hypothesis and second in terms of the effects the lateralization of language representation might have on the representation of spatial functions. PMID- 4027056 TI - The statistical interaction of cerebral specialization and integration in the interpretation of dynamic brain images. AB - Two constructs of brain function, namely cerebral specialization and integration, have been examined in the analysis of blood flow and metabolic function resulting from dynamic imaging procedures. The purpose of the current paper is to illustrate the interaction of these two constructs at the statistical level. Because of the statistical interaction, it is argued that the currently accepted statistical evidence for cerebral specialization is, in fact, partially a function of the degree of regional cerebral integration. Therefore, found asymmetries of flow or rate may be solely a function of cerebral integration. These points are discussed with respect to developing a better understanding of stimulus/brain/behavior relations. PMID- 4027057 TI - Perceptual interference and hemispheric specialization. AB - Two experiments evaluated the effect of stimuli presented at fixation on the recognition of faces or random shapes presented to the left or right visual half field (VF). Increasing the processing demands of the center stimulus produced a large, linear decrease in recognition from both VFs for both faces and shapes. Recognition of random shapes was decreased more in the right visual field by center digits and in the left VF by center faces and shapes. In addition, interference was found between the VF faces and the center digits to the left of fixation. It was concluded that differences in the processing capacity of the two hemispheres are a function of the verbal-nonverbal nature of the stimuli at a later stage in processing but that the two hemispheres may also differ along other perceptual dimensions at an earlier stage of visual recognition. PMID- 4027059 TI - Toward a model of dichotic listening performance. AB - Dichotic listening performance for different classes of speech sounds was examined under conditions of controlled attention. Consideration of the complex of target item and competing item demonstrated that, in general, targets were more accurately identified when the competing item shared no relevant features with it and less accurately identified when the competing item shared place, voice, or manner with the target item. Nasals as well as stops demonstrated a significant right-ear advantage (REA). False alarm rates were very similar for left and right attentional conditions, whereas intrusions from the right ear while attending to the left were far more common than intrusions from the left while attending to the right. Attention is viewed as serving to select the stimuli that will be reported, but at a late stage, and only after the right ear perceptual advantage has had its effect. A model of dichotic listening performance is proposed in which both the ease of localizing the item and the strength of evidence for the presence of the item are relevant factors. PMID- 4027058 TI - Processes of verbal memory failure in Alzheimer-type dementia. AB - Multiple aspects of verbal learning and memory performance in mild as compared to moderate Alzheimer-type dementia (ATD) were studied with the Buschke selective reminding paradigm. Results show that (1) both groups of ATD subjects depend less on long-term memory (LTM) and more on short-term memory (STM) relative to elderly control subjects, (2) mild ATD subjects show less LTM encoding than moderate ATD subjects, (3) moderate ATD subjects retrieve a smaller portion of the items presumed to be encoded into LTM than do mild ATD subjects, and (4) high-imagery words increase LTM encoding and retrieval as compared to low-imagery words for moderate ATD subjects only. These results are explained by the inability of ATD subjects to attend to more than one component of the list-learning task, in conjunction with differences in the deployment of attention between mild and moderate ATD subjects. PMID- 4027060 TI - Processing of faces by patients with unilateral hemisphere lesions. I. Dissociation between judgments of facial affect and facial identity. AB - In this study, right-hemisphere-damaged (RHD) subjects performed significantly worse than LHD and NHD controls across a series of seven facial identity and facial affect tasks. Even when the patient groups were statistically equated on a measure of visuoperceptual ability, the RHD group remained impaired on three emotional tasks--naming, picking, and discriminating emotional faces. These findings suggest that the defects shown by RHD patients on facial affect tasks cannot be solely attributed to defects in visuoperceptual processing and that the right-hemisphere superiority for processing facial affect exists above and beyond its superiority for processing facial identity. PMID- 4027061 TI - Right-hemisphere interactions in picture-word processing. AB - The processing of pictures was investigated in three experiments which eliminated the response effects involved in naming. When a categorization task was used, clear advantages in response latency and accuracy were observed for left visual field (LVF) presentations. This was in contrast to previous investigations which have used a naming task and which have reported right visual-field (RVF) advantages. When a distracting word was added to the display, the pattern of influence also changed from that reported previously. The use of naming tasks has indicated predominantly left-hemisphere effects, with demonstrations of interactions between pictures and words in the RVF. With a categorization task in Experiment 2, however, the only effective words were those related in meaning to the picture, and only when they were projected to the right hemisphere. The third experiment confirmed the LVF advantage for picture processing with masked displays, but found no reliable asymmetry with unmasked presentations. The pattern of semantic facilitation was also confirmed with the masked displays, but when the mask was removed an inhibition effect replaced the facilitation effect. These effects are interpreted as indicating that picture recognition is localized within the right cerebral hemisphere. It is suggested that the facilitating effect of related words is restricted to the left hemisphere because it is an effect upon recognition processes, whereas the inhibition effect reflects response competition. It is also suggested that previous reports of left hemisphere interference effects are due to effects of response competition in naming tasks. PMID- 4027062 TI - Human medial temporal-lobe stimulation disrupts both formation and retrieval of recent memories. AB - Disrupting medial temporal-lobe (MTL) activity for less than a second, either during the initial presentation of a complex scene or when it is presented again 1 min later, severely impairs recognition at the second presentation. MTL disruption during both presentation and recognition periods produces further impairment. These results are not consistent with views limiting MTL function solely to encoding or solely to retrieval mechanisms. PMID- 4027063 TI - Morphologic asymmetries of the face: a review. AB - It has been suggested that asymmetries in the morphological properties of the face contribute to or produce asymmetries in facial emotional expression. Over 50 years of research on hard tissue, soft tissue, and facial surface asymmetries is reviewed here. Generally, it appears that if consistent asymmetry characterizes facial morphology, it is extremely small in magnitude or characterizes regions yet to be examined. In contrast, marked homology and asymmetry in regional size and area has been noted often. At present, it does not appear that asymmetry in facial morphology is associated with facial expressive asymmetry, with the latter more likely to be an outcome of functional brain asymmetry. PMID- 4027064 TI - Parafoveal attention in congenitally deaf and hearing young adults. AB - This reaction-time study compared the performance of 20 congenitally and profoundly deaf, and 20 hearing college students on a parafoveal stimulus detection task in which centrally presented prior cues varied in their informativeness about stimulus location. In one condition, subjects detected a parafoveally presented circle with no other information being present in the visual field. In another condition, spatially complex and task-irrelevant foveal information was present which the subjects were instructed to ignore. The results showed that although both deaf and hearing people utilized cues to direct attention to specific locations and had difficulty in ignoring foveal information, deaf people were more proficient in redirecting attention from one spatial location to another in the presence of irrelevant foveal information. These results suggest that differences exist in the development of attentional mechanisms in deaf and hearing people. Both groups showed an overall right visual field advantage in stimulus detection which was attenuated when the irrelevant foveal information was present. These results suggest a left-hemisphere superiority for detection of parafoveally presented stimuli independent of cue informativeness for both groups. PMID- 4027065 TI - The effects of distance between interactants and subject anxiety on conjugate lateral eye movements. AB - Ehrlichman and Weinberger (1978, Psychological Bulletin 85, 1080-1101) have suggested that the distance between participants during face-to-face interviewing may be a significant determinant of directional patterns of conjugate lateral eye movements (CLEMS). As predicted, at the longer, social distance CLEMS were dependent on the verbal or spatial nature of questions; when interactants were at a closer, personal distance CLEMS became more consistent in direction, regardless of problem type. Distance manipulation also differentially altered CLEM patterns for the two sexes. PMID- 4027066 TI - Feature-processing deficits following brain injury. I. Overselectivity in recognition memory for compound stimuli. AB - A previous experiment (S. Wayland & J.E. Taplin, 1982, Brain and Language, 16, 87 108) demonstrated that aphasic subjects had particular difficulty performing a categorization task, which for normals involves abstraction of a prototype from a set of patterns and sorting of other patterns with reference to this prototype. This study extended the investigation to a recognition memory task similarly organized in categorical structure. The aim was to replicate the previous findings and to delineate the precise nature of aphasics' difficulties with such tasks. Aphasics were again found to be aberrant in performing this task in comparison with normal subjects, nonaphasic brain-injured control subjects also demonstrating a departure from normality. The results suggest that the problem for brain-injured subjects is one of overselectivity in terms of the features of the stimuli to which they respond rather than a difficulty with prototype abstraction itself. PMID- 4027067 TI - Feature-processing deficits following brain injury. II. Classification learning, categorical decision making, and feature production. AB - The claim that overselectivity in feature processing underlies the disorders that aphasics display in processing both visual and verbal material was directly tested by exploring the relationships between the behavior of brain-injured subjects on three experimental tasks: classification learning, categorical decision making, and feature production. From each of these tests a score selected as being indicative of overselective responding was entered into a principal components analysis, together with measures of visual recognition and memory, visual reasoning, naming skills, and severity of aphasia. This analysis supported the assumption that feature-processing disability is a specific and separable deficit, although related both to naming ability and to severity of aphasia. The relevance of the overselectivity hypothesis to naming difficulties following brain injury is discussed. PMID- 4027068 TI - [The role of a child neurologist in Sapporo Child Welfare Center]. PMID- 4027069 TI - [Neuropathology of brainstem in severe cerebral palsy mainly due to perinatal asphyxia]. PMID- 4027070 TI - [A study on development of Landau reaction]. PMID- 4027071 TI - [Cerebral infarction in children. Clinical analysis of functional prognosis in 24 cases]. PMID- 4027072 TI - [Short latency somatosensory evoked potentials to peroneal nerve stimulation in juvenile diabetes mellitus]. PMID- 4027073 TI - [Hereditary motor and sensory neuropathy type I in early childhood. Clinical features and the findings of nerve pathology]. PMID- 4027074 TI - [Neuropathological study of infantile spasms]. PMID- 4027075 TI - [Clinical application of peripheral, spinal and central conduction velocities following stimulation of the posterior tibial nerve]. PMID- 4027076 TI - [Romano-Ward syndrome: two cases treated as epilepsy]. PMID- 4027077 TI - [Hematoma of the basal ganglia in the newborn: non-surgical treatment]. PMID- 4027078 TI - [Optimum dosage regimen of intermittent oral diazepam for the prevention of recurrent febrile convulsions--pharmacokinetics of diazepam after repeated oral administration]. PMID- 4027079 TI - [Head NMR CT in Hand-Schuller-Christian disease]. PMID- 4027080 TI - [A case of hyperCKemia with mounding phenomenon]. PMID- 4027081 TI - [Cerebellar degeneration in chronic alcoholism: with special reference to an autopsied case showing the restricted form of cerebellar cortical degeneration (Victor)]. AB - The brains of 8 patients with chronic alcoholism were neuropathologically examined. The findings obtained in the cerebellum of case 1 (male, aged 52) were in agreement with the restricted form of cerebellar cortical degeneration which was described by Victor et al (1958). The clinicopathological report on the cerebellar degeneration of this type was very rare in Japan. The cerebellar changes were more pronounced in the anterior vermis than in the posterior vermis and hemisphere. Furthermore, some old lesions of Wernicke's encephalopathy were found in this brain. 7 other cases showed very mild cerebellar degeneration. Partial loss of Purkinje cells was found near the tops of cerebellar folia. But their distribution and intensity had no individual variation and there was no tendency that the anterior vermis was more affected. This fact suggests that the alcoholic cerebellar degeneration may have some other cause than the direct toxic effect of ethylalcohol or its metabolites. The etiology of this disease was discussed with reference to thiamine deficiency and mal-nutrition. PMID- 4027082 TI - [Studies on ultrastructural changes in perivascular cells (F.G.P.) of small cerebral vessels at the initial stage after cold injury--chronological observations on F.G.P. within 24 hours]. AB - As the potentiated cells in reaction to cerebral edema and damage, microglia, astrocytes and macrophages had been listed. Recent neuropathological study elucidated that most of cerebral macrophages were derived from blood leucocytes including monocytes. Several years ago, one of the authors reported the presence of histiocytic cells in perivascular space and named them as fluorescent granular perithelial (F.G.P.) cells from their morphological characteristics. The present paper is concerned with the response of the F.G.P. cells to the vasogenic edema induced with cold injury. The animals employed were Wistar male rats aged 3 months. At 2, 6, 10, and 24 hours after the cold injury, cerebral cortex was excised, and specimens were prepared for light and electron microscopical observations. As already reported, the F.G.P. cells included autofluorescent and PAS positive granules. The intracellular granules were rich in hydrolytic enzymes and lack in sudanophile substances. The F.G.P. cells were derived from leptomeningeal cells and acquired uptake capacity for exo- and endogenous substance after birth. In this paper, the F.G.P. cells locating in the boundary between cold injured and healthy regions were observed. At 2 to 10 hours after cold injury, the F.G.P. cells were vacuolated and swollen, and the electron opacity of them decreased moderately. Lipoidal substance appeared in the intracellular granules first at 2 hours and then increased, while the activity of acid phosphatase in them became low in corresponding with a time interval after the cold injury. At this period, occasionally the F.G.P. cells possessed a complicated boundary to astrocytes surrounding them. In general, such morphological changes were reversible and recovered partially around at 24 hours.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4027083 TI - [Cerebrospinal fluid absorption mechanism--based on measurement of CSF flow rate in shunt tube]. AB - The cerebrospinal fluid (CSF) absorption mechanism in cases of hydrocephalus was investigated on the basis of measurements of CSF flow in a shunt tube after ventriculo-peritoneal shunt surgery, monitoring of intracranial pressure, CT findings, radioisotope cisternography, cerebral blood flow, EEG, PSP tests and changes in neurological findings. The subjects were 6 males and 7 females aged from 18 to 70. CSF flow rates in the shunt tubes were between 0.01 and 1.93 ml/min. Calculating the daily volume of CSF flow, the subjects were divided into two groups: Group A (8 patients) with a volume of less than 150 ml/day (0.01-0.25 ml/min), and Group B (5 patients) with between 150 and 500 ml/day (0.01-1.93 ml/min). Monitoring of intracranial pressure prior to the shunt operation was performed in 10 cases. These pressure values ranged between 4 and 25 mmHg (mean: 7-8 mmHg), and there was no difference between the two groups. The pre-and post operative radioisotope cisternography findings indicated improvement of ventricular dilatation, periventricular lucency and ventricular reflux. After the shunt operations, there was neurological improvement in 6 of the 8 Group A cases but only in 2 of the 5 Group B cases. Considering the CSF flow volumes of the two groups, it appears that in Group A the shunt tube is not the main CSF circulation pathway. This could mean that resistance to CSF absorption in the cerebrospinal space has decreased after the shunt operation and there has been recovery of the physiological CSF absorption pathways. In other words, neurological improvement can be expected in this group A. PMID- 4027084 TI - [Threshold of penicillin induced epileptiform afterdischarge in brain slices of guinea pig]. AB - Investigation of the regional threshold for epilepsy in many structures in the brain would contribute to the study of epileptogenesis. So we studied the threshold for epileptiform afterdischarge in the neocortex, hippocampus and cerebellar cortex using Na-Penicillin -G (Pc) of which epileptogenesis has been intensively investigated. In order to eliminate the influence from the outside of these structures, the brain slice method was utilized. Procedures for preparation of the tissue and incubation were about the same as those described by Yamamoto. In summary, after sacrifice, brain of the guinea pig was taken out and the hippocampus, neocortex and cerebellum were cut with a razor blade under a microscope. The thickness of the section was about 0.3 mm. Slices were incubated at 37 degrees C for about 30 min in the standard medium perfused with 95% O2 and 0% CO2. The chamber was continuously perfused with the standard medium which composed of NaCl, 124 mM, KCl, 5: KH2PO4, 1.24; MgSO4, 1.3; CaCl2, 2.4; NaHCO3, 26; and glucose, 10. Evoked potentials were elicited by electrical stimulation in the standard medium. Mossy fibers were stimulated and responses were recorded from the CA3 area in the hippocampus by glass pipette microelectrode. Subcortical white matter was stimulated and responses were recorded from the Purkinje cell layer in the cerebellum. Pc was added in the standard medium until epileptiform afterdischarges were superimposed on the evoked potentials. The results of this experiment demonstrated that each structure in the brain has a regional own threshold for Pc induced epileptiform afterdischarge.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4027085 TI - [Brain lipid metabolism during early period of global ischemia--with reference to the enzymes related to membrane phospholipid metabolism]. AB - It is generally known that free fatty acids (FFA) are liberated from membrane phospholipids in the brain tissue during the early period of ischemia. However, the precise mechanism of FFA liberation from phospholipids is still unclear, even though it is a central topic of neurosurgery. As an initial step toward a better understanding of the molecular mechanism, we have investigated the effects of global ischemia upon brain lipid metabolism. Brain ischemia was evoked by rat decapitation without anesthesia. Removed brains were incubated for 1, 5, 15 or 30 min at 37 degrees C and then quickly frozen in liquid nitrogen. After extraction of total lipids from the brains by Bligh & Dyer's method, the compositions of neutral lipids and phospholipids were analyzed by thin-layer and gas-liquid chromatography. For assaying deacylating enzyme (phospholipase A) activity, the brain homogenate was used as a crude enzyme. The reaction mixture including radioactive substrate, buffer (pH 7.3 & 4.0) and enzyme was incubated for 1 hour at 37 degrees C. Lipids were extracted from reaction mixture and separated by TLC. The enzyme activity was estimated by measuring the radioactivity in FFA or lysophosphatidylcholine liberated from L-alpha-di [1-14C] palmitoyl phosphatidylcholine. The reaction mixture for the assay of reacylating enzyme (acyl CoA: lysophospholipid acyltransferase) activity, contained acyl CoA, lysophosphatidylcholine, DTNB and microsomes, and the enzyme activity was determined by the amount of released CoA-SH detected spectrophotometrically. The results demonstrated that FFA, either unsaturated or saturated, rapidly accumulated in the brain during the early period of ischemia. Di-acylglycerols were also produced in the ischemic brain.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4027086 TI - [The activities of phospholipase A, PI-specific phospholipase C, lipase, lysophospholipase and acylCoA: lysophospholipid acyltransferase in ischemic brain microsomal fraction]. AB - It has been well recognized that acyl groups of phospholipids play an important role for structure and function of biomembrane. The turnover of these acyl groups in normal brain biomembrane is also well known. Some types of enzymic system related to this turnover has been investigated. Phospholipase A, PI-specific phospholipase C, lipase, lysophospholipase and acylCoA: lysophospholipid acyltransferase belong to these enzymic systems. In this report, the sequential changes of phospholipase A, PI-specific phospholipase C, lipase, lysophospholipase and acylCoA: lysophospholipid acyltransferase activities in ischemic rat brain were examined. The purpose of this study was to examine the enzymic changes of deacylation-reacylation cycle of biomembrane phospholipid in ischemic brain. Ischemic brain were produced by decapitation and activities of 5 enzymes were assayed in microsomal fraction. The activities of phospholipase A, PI-specific phospholipase C, lipase showed high value during early stage of ischemia for 15 or 30 min and then decreased gradually. Lysophospholipase activity was not changed for 120 min. On the other hand, acylCoA: lysophospholipid acyltransferase activity showed gradual decrease from the beginning of ischemia. There are some reports that in early ischemic stage, the concent of free fatty acids increase, while that of phospholipid decrease. The present results may suggest that the changes of free fatty acid and phospholipid in ischemic brain are related to these enzymic system. PMID- 4027087 TI - [Diagnosis of spinal diseases with magnetic resonance imaging]. PMID- 4027088 TI - [Intracranial anomalies in myelomeningocele--observation with magnetic resonance (MR) imaging]. AB - It is generally accepted that myelomeningocele frequently associates with Arnold Chiari malformation and other anomalies of the intracranial structures. The ventriculographic and CT findings of the patients with myelomeningocele has been reported. Magnetic resonance (MR) imaging is useful to observe the coronal and sagittal images of the brain in order to speculate the etiological mechanism of myelomeningocele and its associated anomalies. We experienced three cases of myelomeningocele and reviewed their MR images using coronal and sagittal tomography in spin echo and inversion recovery technique. The morphological detail of MR images as to the intracranial structures was presented. Possible mechanism of the anomalous structures of the brain in myelomeningocele was also described. PMID- 4027089 TI - [Myelin formation of the dorsal root ganglion cells of the senile rat in long term culture]. AB - Using the dorsal root ganglia (DRG), long-term cultures were done in neonatal (control) and senile (experimental) rats. The morphological analysis on myelin sheath formation was carried out by light microscopy, electron microscopy and image analyzing apparatus. The results are as follows: The neurites of senile DRG cells appeared 7 days later than the neurites of neonatal DRG cells. While the myelinations were observed in neonatal DRG culture by the third week, myelinations of senile DRG were also formed 7 days later. The myelin sheaths in both neonatal and senile DRG cultures looked much like those which were formed in vivo, but the number of myelinations in senile DRG culture was fewer than that of the neonatal DRG culture. In observations by electron microscopy, myelin lamellae numbered about 20 in both neonatal and senile DRG cultures with normal-appearing axon structures as seen in vivo. The discontinuities in the external lamina of Schwann cells were not observed in both the neonatal and senile DRG cultures. In the morphological analysis of neonatal and senile DRG cultures, the internodal length, diameter of myelin sheath and the length of nodal gap (distance between the rounded end of the compact myelin) were measured by image analyzing apparatus (MAGISCAN-I, Joyce Loebl LTD.) with Sudan black B stain. Although the internodal length of myelin sheath in senile DRG culture (144.9 +/- 40.7 microns) proved to be significantly longer than the neonatal DRG culture (131.6 +/- 26.2 microns) (p less than 0.01), the diameter of myelin sheath showed no significant difference between neonatal (2.9 +/- 0.7 micron) and senile (2.8 +/- 0.7 micron) DRG.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4027090 TI - Histomorphometric changes in the trabecular structure of a selected stress region in the femur in patients with osteoarthritis and fracture of the femoral neck. AB - Histomorphometric changes in the trabecular structure of the principal compressive stress region in the femur in patients with osteoarthritis and fracture of the femoral neck are described. Femoral heads were obtained from patients who had surgery for the treatment of femoral neck fracture or total hip replacement for advanced osteoarthritis. Blocks from the principal compressive region of a coronal slice were sampled systematically to prepare 10 microns sections for automated analysis. There was no significant difference in the mineral bone content of the osteoarthritic (OA) and fractured neck of femur (FNOF) cases or between males and females for each group. The regression of mineralized bone on age was significant for OA data, showing a decrease in mineralized bone volume with age, whereas there was no significant relationship for the FNOF data. Surface density was significantly lower in the OA group than in the FNOF group despite the fact there is no difference in the mineralized bone. The regression of surface density on age was not statistically significant in both groups, although regression of surface density on the mineralized bone was significant for both groups and demonstrated that OA cases generated less surface than FNOF cases for the same amount of mineralized bone volume. The trabeculae in OA were significantly thicker than in FNOF, and spacing in OA was significantly greater than in FNOF. The regression of trabecular thickness and spacing on age was not significant for either OA or FNOF. For OA, thickness and spacing showed a significant regression on the mineralized bone volume, positive and negative, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4027092 TI - Trabecular bone resorption depth decreases with age: differences between normal males and females. AB - The resorption depth below osteoclasts, mononuclear cells, and preosteoblast-like cells can be estimated by counting the number of lamellae of known thickness eroded below the three cell types. In a previous study on bone resorption in young normal individuals, we demonstrated that the mean depth below osteoclasts was smaller than the mean depth below mononuclear cells, which again was smaller than the mean depth below preosteoblast-like cells, the last taken as the final depth reached. In order to investigate the variation in resorption depth with age in both sexes, we examined bone biopsy specimens from 42 normal females and 34 normal males aged 17-90 years. For each patient the mean osteoclastic, mononuclear, and preosteoblast-like cell resorption depths were calculated, and the surface extensions of the three types of resorption lacunae were determined. The surface extent of preosteoblast-like cell lacunae increased with age in females (p less than 0.05). Osteoclastic resorption depth was constant throughout the ages in females as well as in males. Mononuclear and preosteoblast-like cell resorption depths decreased significantly with age in females (p less than 0.01 and p less than 0.05, respectively) as well as in males (p less than 0.05 and p less than 0.01, respectively). The mean depth of lacunae where resorption had terminated (i.e., preosteoblast-like cell resorption depth) was larger in females aged 30-60 years than in men of the same age (p less than 0.05). The reduction in final resorption depth with age is parallel to the decrease in mean thickness of completed walls previously described.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4027091 TI - Prevalence of bone demineralization in the United States. AB - A study of the distribution and prevalence of bone demineralization in the US population is reported. Based on the HANES I Survey data that incorporated bone density examination of V-2 by the Goldsmith and Vose techniques in a national sample of 6030 adults, it was observed that (1) age-adjusted bone density differences between sexes were consistently found when controlling for race (the prevalence of low bone density was greater among females than males) and (2) whites of both sexes had higher prevalence of low density than blacks in most age sex categories. PMID- 4027093 TI - A classification of in vivo bone labels after double labeling in canine bones. AB - Labeling patterns were classified after double bone labeling of four male beagles, 10 months of age. Calcein and oxytetracycline were given on the 18th and the 7th day prior to simultaneous iliac and 11th rib biopsies. Undecalcified sections stained with the Villanueva bone stain were studied by epifluorescence microscopy. Five structures were identified and classified: the first or green label, the interlabel layer of mineralized bone, the second or yellow label, the post double-labeled mineralized bone layer, and osteoid seams. Doubly plus singly labeled surface equalled 40.8 +/- 8.4% of the total trabecular surface of the ilium. Doubly labeled surface as a percent of the total labeled surfaces equaled 55.5% in trabeculae and 68.1% in osteons, whereas green first-singly labeled surface equaled 24.2% and 11.9%, respectively, and yellow second-singly labeled surface equaled 20.3% and 20.0%, respectively. Unequivocal examples appeared in both biopsy sites of all four dogs of bone-forming systems that lacked one or the other label, or both, and also of systems in which cessation of mineralization or of new matrix formation occurred between the two labels and between the second label and the day of biopsy. The findings prove that the On-Off states in active bone-forming sites that have been postulated by other investigators do exist. Since widely different labeling patterns appeared in different bone-forming centers in the same bone and the same animal, a local factor rather than a systemic one should control those differences at the level of the BMU. PMID- 4027095 TI - Lipid changes in the bones of the healing vitamin D-deficient phosphate-deficient rat. AB - The bones of vitamin D-deficient, phosphate-deficient rats have a lipid composition that is significantly different from that of normal bones. Specifically, these bones have elevated cholesterol and reduced lysophosphatide and free fatty acid contents. Treatment of these animals with a single dose of vitamin D and phosphate produces healing within 72 h and causes rapid corrections of alterations in growth plate and cancellous bone lipid composition. Healing of the rachitic/osteomalacic state in these animals was demonstrated radiographically and histologically. Histomorphometric measurements showed that the relative osteoid volume of the cancellous bone rapidly approached the 7% value of normal controls, decreasing from 29% in the rachitic animals to 16% by 12 h and 8.5% by 72 h. Significant changes in ash weight, Ca:P ratio, and crystal lite size and perfection were detectable at 12 h, with these parameters approaching values found in normal animals within 72 h. Calcium-acidic phospholipid-phosphate complexes, which are known to promote hydroxyapatite formation, peaked in concentration at 12 h in epiphysis, cancellous, and cortical bone, returning rapidly to normal values after that time. In untreated animals the complexed acidic phospholipid content of the nonmineralized epiphysis was comparable to that in normal mineralizing epiphysis, whereas the content of the complexes was reduced in the cancellous bones of the untreated animals. PMID- 4027094 TI - The influence of dietary calcium on kidney calcification and renal function in rats fed high-phosphate diets. AB - This study was carried out to test the hypothesis that kidney calcification caused by high dietary phosphorus intake can be prevented by increasing the calcium content of the diet, because the latter reduces the intestinal P absorption. The investigation was conducted in rats fed semipurified diets with either a low (0.15%) or a high (1.20%) P content. Although dietary Ca supplementation (as CaCO3 or CaCl2) reduced the intestinal P absorption, it did not prevent kidney calcification induced by high dietary P. On the contrary, when CaCO3 was supplemented for 16 weeks, renal calcification increased, probably due to the alkaline nature of this salt. Both CaCO3 and CaCl2 in the high-P diets adversely influenced Mg use. This might explain the failure of these salts to prevent kidney calcification. PMID- 4027097 TI - Inhibition of bone matrix apposition by (3-amino-1-hydroxypropylidene)-1,1 bisphosphonate (AHPrBP) in the mouse. AB - To elucidate the mechanism of action of (3-amino-1-hydroxypropylidene)-1,1 bisphosphonate (AHPrBP, formerly APD) on bone metabolism, we have studied the influence of low doses of AHPrBP on bone resorption and formation in the mouse. Thirty-five-day-old mice were given daily injections of 0.16, 1.6, or 16 mumol/kg BW per day of AHPrBP for 10 days. At sacrifice biochemical parameters were measured in serum and bone ash, and histomorphometric parameters of bone formation and resorption were determined on undecalcified sections of caudal vertebrae after double 3H-proline and double tetracycline labelings. Serum calcium and 1,25-dihydroxyvitamin D levels remained normal at all dosage levels. Compared to controls, AHPrBP at doses of 1.6 and 16 mumol/kg per day increased the number of osteoclasts and the number of nuclei per osteoclast but markedly decreased the number of acid phosphatase-stained osteoclasts. Thus, AHPrBP appears to inhibit osteoclastic activity in vivo in part through reduction of acid phosphatase activity. At doses of 1.6 and 16 mumol/kg per day AHPrBP reduced serum alkaline phosphatase and the osteoblastic surface and decreased the endosteal osteoid surface and thickness. Both the matrix apposition rate and the mineral apposition rate were progressively reduced at the endosteal level, although they were not significantly changed at the periosteal level. Greater inhibition of bone resorption than bone formation resulted in increased endosteal bone density and bone mineral content. AHPrBP at a dose of 0.16 mumol/kg per day did not alter either the osteoclastic bone resorption or the mineral and matrix apposition rates. PMID- 4027096 TI - Isolation of matrix vesicles by isoelectric focusing in Pevikon-Sephadex. AB - We have investigated the use of an isoelectric focusing (IEF) technique for isolating and characterizing matrix vesicles. Focusing was performed on crude preparations of matrix vesicles isolated from collagenase digests of chick epiphyseal cartilage and purified by discontinuous sucrose gradient centrifugation. Crude and partially purified vesicle preparations were subjected to flat bed IEF in a slurry of Pevikon-Sephadex. Partially purified matrix vesicles focused as a narrow band (pI congruent to to 6.5). Alkaline phosphatase, solubilized from matrix vesicles, focused with a pl of 4.0-4.5. The IEF profile of matrix vesicles also differed from that of chondrocyte membranes. Thus, the membrane pls were congruent to to 5.4 and 6.6-7.8, respectively. The latter peak probably corresponded to the pl of the matrix vesicle preparation. This observation lends support to the view that vesicles originate from distinct regions of the chondrocyte membrane. PMID- 4027098 TI - Evoked responses--a neurophysiological indicator of depth of anaesthesia? PMID- 4027099 TI - Cerebral electrical activity influences the effects of etomidate on cerebral perfusion pressure in traumatic coma. AB - The effects of 124 boluses of etomidate 0.2 mg kg-1 i.v. on intracranial pressure (ICP), mean arterial pressure (MAP) and cerebral perfusion pressure (CPP) were studied in eight patients with severe head injury (Glasgow coma score less than 8). The data were divided into two groups based on the minimum voltage of the cerebral function monitor (CFM) recording before the bolus. In group A this was less than 5 microV (representing profound cortical electrical depression), while in group B the minimum voltage was greater than 5 microV. The mean decrease in ICP following etomidate was significantly greater in group B (mean +/- SEM: -8.6 +/- 0.7 mm Hg) than in group A (-3.8 +/- 0.6 mm Hg) (P less than 0.0001). The decrease in arterial pressure was similar in both groups. Consequently, there was a small mean increase in CPP in group B (2.2 +/- 0.9 mm Hg), whereas in group A CPP decreased (-4.7 +/- 1.5 mm Hg) (P less than 0.001). There was a strong correlation between the decreases in ICP and MAP in group A (r = 0.70, P less than 0.01), but not in group B (r = 0.05). Thus, when cortical electrical activity was already maximally suppressed, further administration of an i.v. anaesthetic agent produced only relatively small decreases in ICP, largely as a passive response to decreases in MAP. CPP was therefore usually reduced. Conversely, in the absence of such depression larger decreases in ICP, unrelated to hypotension, occurred and these were usually associated with increases in CPP. However, even under these circumstances, potentially dangerous decreases in CPP may be seen. PMID- 4027100 TI - Depression of cortical somatosensory evoked potentials by nitrous oxide. AB - The effects of the inhalation of 50% nitrous oxide on somatosensory evoked potentials during a fentanyl-oxygen anaesthetic technique for central nervous system surgery were evaluated. The latency and amplitude of the first cortical wave were obtained using conventional somatosensory techniques with median or posterior tibial nerve stimulation. Data were collected before and after the inhalation of 50% nitrous oxide in oxygen introduced at the conclusion of the surgical procedure. The addition of nitrous oxide was associated with consistent decreases in the amplitude of somatosensory evoked potentials, but with no significant changes in latency. Since no electrical, physiological, or surgical event was associated with these changes, the results suggest that they were attributable to nitrous oxide per se. PMID- 4027101 TI - Effects of anaesthetic technique on deep vein thrombosis. A comparison of subarachnoid and general anaesthesia. AB - Forty patients with fractured neck of femur were allocated randomly to undergo surgery under general anaesthesia (GA) or subarachnoid anaesthesia (SAB). After operation, the incidence of deep vein thrombosis (DVT), assessed by venography, was found to be 40% in the SAB group, which was significantly lower than the incidence (76.2%) in the GA group. These observations may account for the previously reported effect of SAB, in comparison with GA, in reducing early postoperative mortality in this category of patient. PMID- 4027102 TI - Morphine sulphate slow release. Comparison with i.m. morphine for postoperative analgesia. AB - Eighty patients undergoing abdominal surgery were studied after operation. Morphine was administered regularly every 4 h by either the i.m. (morphine sulphate 10 mg) or the oral route (MST Continus 20 mg) in a double-blind double dummy trial. Both MST and i.m. morphine provided satisfactory postoperative analgesia, but significantly greater amounts of supplementary i.m. morphine were required in the MST group. More adverse effects were reported by the patients in the i.m. morphine group. The mean serum morphine concentration in 12 patients in the MST group was 1.7 ng ml-1 at 08.00 h and 19.5 ng ml-1 at 16.00 h on the 1st day after operation, suggesting impaired gastric emptying in the early postoperative period. It is therefore recommended that further studies of the bioavailability of MST in the early postoperative period be undertaken before any recommendations are made regarding its routine use for pain relief at that time. PMID- 4027103 TI - Pharmacokinetics of phenoperidine in anaesthetized patients undergoing general surgery. AB - The pharmacokinetics of phenoperidine have been studied in five anaesthetized patients receiving a 2-mg bolus dose i.v. Plasma concentrations were measured using a sensitive radioimmunoassay method. The distribution of phenoperidine was described according to a two-compartment open model. The mean distribution half life (T1/2 alpha) for the five patients was short (2.2 min); the mean elimination half-life (T1/2 beta) was 193 min. The mean whole body clearance was 22 ml min-1 kg-1 and the apparent steady state distribution volume (VSS) was 5.7 litre kg-1. Secondary concentration peaks occurred in all patients; in two patients these were substantial and occurred 80 min after injection. PMID- 4027104 TI - Pharmacokinetics of phenoperidine in patients undergoing cardiopulmonary bypass. AB - Phenoperidine concentrations were studied, using radioimmunoassay, in five patients submitted to coronary artery bypass graft surgery. Administration of phenoperidine consisted of a 5-mg bolus dose followed by constant infusion of 5 mg h-1. Before cardiopulmonary bypass, phenoperidine concentrations were stable in an individual patient, but there was a large scatter between patients. The concentrations decreased immediately following the start of the bypass, but this decrease was short. During cardiopulmonary bypass, the phenoperidine concentrations increased progressively and were greater at the end of the bypass than before it. The increase in concentration continued following the discontinuation of bypass. The ratios of change of the observed results were in accord with a theoretical evaluation, although the observed concentrations were all greater than those calculated, except at one point. This difference in phenoperidine concentration is probably related to an alteration of liver plasma flow. Haemodilution as a result of the priming of the cardiopulmonary bypass circuit played only a transient role. PMID- 4027105 TI - Extradural analgesia in the management of singleton breech delivery. AB - Ninety-four singleton vaginal breech deliveries conducted under extradural analgesia were compared with 277 singleton vaginal breech deliveries conducted without extradural analgesia. Mean duration of the first stage of labour was similar in both groups. Mean duration of the second stage of labour was prolonged and mean 1-min Apgar scores were less in fetuses weighing more than 2500 g in the extradural group. Mean 5-min Apgar scores, perinatal morbidity and maternal complications were similar in both groups. PMID- 4027106 TI - Effect of halothane on spinal somatosensory evoked potentials in sheep. AB - The effects of increasing concentrations of halothane on the morphology of spinal somatosensory evoked potentials (SEP) were studied in seven anaesthetized sheep. Anaesthesia was induced with thiopentone and maintained with nitrous oxide in oxygen. Ventilation was controlled throughout. Arterial pressure, temperature and end-tidal carbon dioxide tension were monitored. A lumbar laminectomy was performed, the sciatic nerve exposed and a baseline spinal SEP was recorded from the surface of the lumbar spinal cord. Halothane was introduced in incremental steps of 1% up to 3% and further SEP were recorded. These recordings revealed that the spinal SEP peak latencies and general waveform configuration were stable under halothane anaesthesia. Baseline SEP amplitude was similar to that obtained with 1% halothane; however, at concentrations of 2% halothane or greater, there was a significant (P less than 0.005) attenuation of all components of the spinal SEP. These findings have important anaesthetic implications for patients undergoing spinal cord monitoring using SEP, although interspecies differences may occur. PMID- 4027107 TI - Laboratory evaluation of low-pressure tracheal tube cuffs: large-volume v. low volume. AB - Large- and low-volume low-pressure tracheal tube cuffs were compared during exposure to nitrous oxide. The compliance of both types of cuff when measured inside and outside an artificial rigid trachea, the volume of intubated cuff, the residual volume, the nitrous oxide diffusion time, and the specific diffusion rate of the cuff membrane to nitrous oxide were measured in the laboratory. From these variables, the diffusion rate of nitrous oxide, the surface area available for nitrous oxide diffusion, the tracheal wall pressure exerted by cuff, and the degree of folding of the intubated cuff were derived. The results showed that the rapid increase in pressure of the large-volume cuff when intubated was caused by low compliance, the large surface area available for nitrous oxide diffusion, and the considerable permeability of the cuff membrane to nitrous oxide. PMID- 4027108 TI - Monitoring of brainstem auditory evoked potentials during basilar artery occlusion in man. AB - Brainstem auditory evoked potentials (BAEP) were recorded during surgery as a monitor of brainstem function in three patients undergoing posterior fossa surgery for clipping of basilar aneurysms. In two patients, ligation of the basilar artery, and of a vertebral artery, was associated with deterioration in BAEP and resulted in postoperative brainstem dysfunction. In the third patient, postoperative transient neurological dysfunction occurred following temporary occlusion of the basilar artery and this correlated with intra- and postoperative changes in BAEP. BAEP monitoring is recommended where temporary or permanent occlusion of the vertebrobasilar system is planned. PMID- 4027109 TI - Effect of naloxone on loss of consciousness induced by i.v. ketamine. PMID- 4027110 TI - 'Esophageal Gastric Tube Airway'--a potential hazard. PMID- 4027111 TI - Hypoglycaemia in children undergoing outpatient procedures. PMID- 4027112 TI - Metastatic carcinoma in the extradural space. PMID- 4027113 TI - CSF pharmacokinetics of extradural morphine. PMID- 4027114 TI - Ventricular arrhythmias and adrenaline infiltration during gynaecological surgery. PMID- 4027115 TI - Attempts to phenotype human liver samples in vitro for debrisoquine 4-hydroxylase activity. AB - Twenty-eight samples of human liver have been characterised for cytochrome P-450 content, aldrin epoxidase, debrisoquine 4-hydroxylase and bufuralol 1' hydroxylase activities. Evidence is presented here and elsewhere that bufuralol 1'-hydroxylase and debrisoquine 4-hydroxylase are activities catalysed by the same form of cytochrome P-450 in man, and that this form is different from that catalysing the epoxidation of aldrin. Attempts to phenotype liver samples in vitro, in the absence of any metabolic data in vivo for debrisoquine 4 hydroxylation status, met with limited success. A combination of enzyme assays will most probably be required in any such phenotyping of human liver samples. PMID- 4027116 TI - Effects of verapamil on calcium-induced rigidity and on filterability of red blood cells from healthy volunteers and patients with progressive systemic sclerosis. AB - The effects of verapamil on calcium-induced decrease deformability of red blood cells (RBCs) and on the filterability of RBCs from healthy volunteers and patients with progressive systemic sclerosis (PSS) were investigated in vitro using a gravity driven filtration technique. The filterability of RBCs was increased by verapamil 1 microgram/ml (P less than 0.01) in healthy volunteers (P less than 0.05) and in patients with PSS (P less than 0.05). A high concentration of verapamil (200 micrograms/ml) caused an 80% reduction (P less than 0.05) in the filterability of RBCs from healthy volunteers. The filterability of RBCs stored at 4 degrees C for 24 h was increased by 1 microgram/ml verapamil (P less than 0.05). Verapamil (1 microgram/ml) prevented the decrease in deformability of RBCs due to an increase in either extracellular or intracellular calcium concentrations (P less than 0.05). By increasing red cell filterability verapamil may be useful in the treatment of PSS and other peripheral vascular diseases where decreased red cell deformability may play an important role in the pathogenesis. PMID- 4027117 TI - Pharmacokinetics of primaquine in man. I. Studies of the absolute bioavailability and effects of dose size. AB - The pharmacokinetics of primaquine have been examined in five healthy volunteers who received single oral doses of 15, 30 and 45 mg of the drug, on separate occasions. Each subject received an i.v. tracer dose of [14C]-primaquine (7.5 microCi), simultaneously with the 45 mg oral dose. Absorption of primaquine was virtually complete with a mean absolute bioavailability of 0.96 +/- 0.08. Elimination half-life, oral clearance and apparent volume of distribution for both primaquine and the carboxylic acid metabolite were unaffected by either dose size, or route of administration. The relationships between area under the curve and dose size were linear for both primaquine (r = 0.99, P less than or equal to 0.01) and its carboxylic acid metabolite (r = 0.99, p less than or equal to 0.01). The mean whole blood to plasma concentration ratios were determined for primaquine (0.81), and for the carboxylic acid metabolite of primaquine (0.84). Primaquine is a low clearance compound (CL = 24.2 +/- 7.4 l h-1), is extensively distributed into body tissues (V = 242.9 +/- 69.5 l) and is not subject to extensive first pass metabolism. PMID- 4027118 TI - Pharmacokinetics of primaquine in man. II. Comparison of acute vs chronic dosage in Thai subjects. AB - We have investigated the pharmacokinetics of primaquine after acute and chronic administration of the drug to five healthy Thai volunteers. After acute dosage (15 mg p.o.) mean (+/- s.d.) peak plasma concentrations of 65.0 +/- 34.7 ng ml-1 were achieved within 2 +/- 1h. Thereafter plasma drug concentrations declined monoexponentially with a mean elimination half life of 4.4 +/- 1.4 h. The mean (+/- s.d.) oral clearance was 37.6 +/- 15.5 1 h-1. These values are in broad agreement with values obtained in healthy Caucasians after administration of an equivalent dose of primaquine. Repeated dosing with primaquine had no effect on the mean pharmacokinetic parameters calculated for this drug. In contrast, individual pharmacokinetic parameters for some subjects exhibited gross and unpredictable changes after chronic dosage. The carboxylic acid metabolite of primaquine accumulated in plasma after repeated dosing such that by day 14 of chronic dosing the mean AUC (0,24) for this metabolite was 74% greater than that obtained after acute administration of primaquine. PMID- 4027119 TI - The pharmacokinetics of high dose metoclopramide in patients with neoplastic disease. AB - High dose metoclopramide infusions (10 mg/kg) were administered to nineteen patients with bronchial carcinoma who were receiving intravenous cyclophosphamide as single agent chemotherapy. Considerable interindividual variability in metoclopramide disposition was observed. Mean clearance was 0.33 +/- 0.13 (s.d.) l h-1 kg-1, mean volume of distribution at steady state was 3.8 +/- 1.2 (s.d.) l/kg and mean elimination half-life was 8.3 +/- 4.4 (s.d.) h. These results were significantly different from mean values previously reported for young healthy volunteers given conventional doses (0.70 l h-1 kg-1, 2.2 l/kg and 2.6 h respectively). Significant correlations were found between serum urea, serum creatinine and metoclopramide clearance. The metoclopramide regimens were well tolerated and, with the exception of two patients, were completely effective in the prevention of nausea and vomiting. To achieve and maintain target serum metoclopramide concentrations of 1 microgram/ml, we now administer a loading infusion of 3.61 mg/kg over 30 min followed by a maintenance infusion of 0.36 mg kg-1 h-1 for 10 h. Cyclophosphamide is normally administered concurrently with the second infusion. For patients with evidence of mild renal impairment, the maintenance infusion rate of metoclopramide hydrochloride should be adjusted according to the predicted individual clearance value; CL (l h-1 kg-1) = 0.57 - [0.036 X urea (mmol/l)]. PMID- 4027120 TI - Effect of charcoal-drug ratio on antidotal efficacy of oral activated charcoal in man. AB - The effect of charcoal-drug ratio on the antidotal efficacy of oral activated charcoal was studied in six healthy volunteers in a randomized cross-over study and compared with the adsorption capacity of activated charcoal in vitro. Aminosalicylic acid (PAS) 1 g and 5 g were ingested on an empty stomach in 30 ml of water. Immediately afterwards the subjects ingested 50 g of activated charcoal in 300 ml of water or 300 ml of water only. PAS 10 g 20 g were only given with 50 g of activated charcoal administered immediately afterwards. The plasma concentrations and the cumulative excretion of PAS into urine were measured for 48 h. Increasing the dose of PAS from 1 g to 20 g reduced the antidotal efficacy of activated charcoal: at a charcoal-drug ratio of 50:1 under 5% of the dose was absorbed but at a ratio of 2.5:1 about 37%. These data correlated well to the saturation of adsorption capacity of charcoal in vitro. To minimize the possibility of saturation of the adsorption capacity of charcoal in acute intoxications where the amount and type of drug taken is usually unknown, large doses (50-100 g) of activated charcoal should be used. PMID- 4027121 TI - Chlorpromazine--a specific effect on breathlessness? AB - Previous work has left unresolved questions on whether promethazine reduces the sensation of breathlessness. This study was designed to provide a definitive answer and to determine the contributions from promethazine's major pharmacological actions. Twelve healthy subjects participated in a double-blind, within-subject comparison of promethazine and placebo each given acutely by mouth. Breathlessness was assessed with visual analogue scales during a progressive exercise test and was related to minute ventilation. Promethazine had no significant effect on breathlessness nor on the relationship between breathlessness and ventilation. The role of histamine-antagonism was investigated in a subgroup of the subjects by administration of mebhydrolin. No effect on breathlessness was detected. In contrast, the standard phenothiazine, chlorpromazine, caused a marked and statistically significant reduction in breathlessness without affecting ventilation and without causing detectable sedation. This unexpected finding merits further study in patients and is discussed with reference to the role of chlorpromazine as a constituent of Brompton's Mixture. PMID- 4027122 TI - Hyper-responsiveness of eccrine sweat glands to carbachol in anxiety neurosis: comparison of male and female patients. AB - The responsiveness of eccrine sweat glands to intradermally injected carbachol was studied in six male and six female healthy volunteers and six male and six female patients suffering from anxiety neurosis. Consistently greater responses to carbachol were obtained in the healthy males than in the healthy females. Analysis of the dose-response curves showed that this was reflected in a higher value of Emax in the males. Consistently greater responses to carbachol were obtained in the anxious males than in the healthy males, this being reflected in a higher value of Emax for the anxious subjects. Consistently greater responses to carbachol were obtained in the anxious females than in the healthy females, this being reflected in a higher value of Emax for the anxious subjects. In contrast to the results obtained with the healthy subjects, there was no sex related difference in responsiveness to carbachol among the anxious patients. It is suggested that the hyper-responsiveness of sweat glands in anxiety states involves the sensitization of normally 'dormant' sweat glands by impulse flow in sudomotor sympathetic fibres. The upper limit to the value of Emax for carbachol, which may be determined by the number of potentially responsive glands, may be similar in the two sexes. PMID- 4027123 TI - The ex vivo plasma protein binding of theophylline in renal disease. AB - The plasma protein binding of theophylline was measured in 21 patients with renal disease and 21 healthy age and sex matched controls. The percentage of theophylline unbound to plasma was greater in patients with nephrotic syndrome and in chronic renal failure than in controls. In nephrotic syndrome the impairment of drug binding mirrored the marked degree of hypoalbuminaemia seen in this condition but in chronic renal failure the impairment of protein binding was greater than would be expected from the plasma albumin concentration changes. The percentage of theophylline free in plasma in renal disease may be increased (by as much as 50%). Such changes should be taken into account in interpreting the relationship between total plasma theophylline concentration and drug effect in renal disease. PMID- 4027125 TI - The effect of activated charcoal and hyoscine butylbromide alone and in combination on the absorption of mefenamic acid. AB - Mefenamic acid 500 mg orally was administered to nine healthy volunteers on four occasions 7 days apart. On two occasions allocated at random, activated charcoal (2.5 g of medicoal) was administered 1 h after the drug. Hyoscine butylbromide (20 mg intramuscularly) was given immediately after mefenamic acid on one of these occasions, and on one occasion after mefenamic acid without charcoal. Hyoscine significantly delayed the time to maximum mefenamic acid concentrations but did not affect the area under the plasma concentration-time curve. Charcoal reduced the area under the plasma concentration curve by 36% and charcoal and hyoscine reduced the area under the plasma concentration curve by 42% from their respective control values. We conclude that early charcoal administration in a ratio of 5 g to 1 g of drug effectively reduces the area under the plasma concentration-time curve after oral mefenamic acid administration. Early charcoal administration may be of value therefore in reducing the toxicity of mefenamic acid after deliberate or accidental overdosage. PMID- 4027124 TI - Plasma concentrations of nortriptyline and its 10-hydroxy metabolite in depressed patients--relationship to the debrisoquine hydroxylation metabolic ratio. AB - In 20 depressed patients treated with nortriptyline (NT) there was a significant relationship between the plasma concentration of NT and the debrisoquine metabolic ratio (rs = 0.77; P less than 0.01). (The debrisoquine test was performed after stopping NT treatment). This is in agreement with the hypothesis that the hydroxylations of NT and debrisoquine are mediated by similar enzymatic mechanisms. In contrast there was no significant relationship between the debrisoquine metabolic ratio and the plasma concentrations of the active metabolite 10-hydroxy-nortriptyline. In 11 of the patients the debrisoquine metabolic ratio was significantly higher during than after NT treatment. This may be due to an inhibition of the debrisoquine hydroxylation by NT. PMID- 4027126 TI - Chronopharmacokinetics of paracetamol in normal subjects. AB - The chronopharmacokinetics of paracetamol was studied in six male volunteers. Serum concentrations of paracetamol were determined after a single oral dose of 1 g, on three occasions, spaced at least 1 week apart. Plasma drug concentration vs time curves were obtained after dosage at 08.00 h (Day 1), 14.00 h (Day 2) and 20.00 h (Day 3), under standardized conditions. Pharmacokinetic parameters compared were t1/2,alpha, t1/2,Z, tmax, Cmax and AUCpo. No statistically significant differences were found. PMID- 4027127 TI - The influence of cimetidine and ranitidine on the plasma lipid pattern. AB - The influence of H2-receptor antagonist drugs on the plasma lipid pattern has been studied prospectively in 51 patients treated with cimetidine (26 patients) or ranitidine (25 patients) for gastroenterological diseases. Total and HDL cholesterol and total triglycerides have been measured. Ranitidine did not influence the investigated parameters, while cimetidine produced a significant increase in the HDL cholesterol serum concentration (P = 0.008). PMID- 4027128 TI - Fenfluramine delays gastric emptying of solid food. AB - The effect of a single dose of (+/-)-fenfluramine hydrochloride (40 mg) on gastric emptying of a mixed solid and liquid meal was assessed with a dual isotope scintigraphic technique in eight obese patients. Fenfluramine significantly delayed gastric emptying of solid food (approximately a 15% reduction in the solid linear emptying rate), but had no effect on gastric emptying of liquid. PMID- 4027129 TI - The cardiovascular effects of regular and decaffeinated coffee. AB - In a single-blind study the effects of drinking two cups of regular or decaffeinated coffee on blood pressure, heart rate, forearm blood flow and plasma concentrations of caffeine, renin and catecholamines were studied in 12 normotensive subjects. Drinking regular coffee led to a rise of blood pressure, a fall of heart rate and an increase of plasma catecholamines. Decaffeinated coffee induced a smaller increase of diastolic blood pressure without changing other parameters. This study shows that the cardiovascular effects of drinking coffee are mainly the result of its caffeine content. PMID- 4027130 TI - Drug metabolite kinetics: noncompartmental analysis. PMID- 4027131 TI - Excretion of disopyramide in human breast milk. PMID- 4027132 TI - Mexiletine clearance during peritoneal dialysis. PMID- 4027133 TI - Effect of ranitidine on procainamide disposition. PMID- 4027134 TI - Correction equation for QT interval. PMID- 4027136 TI - Ranitidine does not alter pethidine disposition in man. AB - The effect of concurrent ranitidine administration on the disposition of pethidine was investigated in eight healthy male volunteers (19-33 years). The subjects received 70 mg i.v. pethidine HCl doses before and during ranitidine treatment (150 mg p.o. twice daily). Ranitidine therapy was not associated with significant alterations in pethidine elimination rate constant, volume of distribution at steady state, total body clearance, and 24 h urinary excretion. No alteration in pethidine oxidation to norpethidine was noted, as suggested by nonsignificant changes in lag time to appearance of quantifiable norpethidine in serum, time to peak concentration, peak concentration, area under the curve from time 0.24 h, and 24 h urinary excretion. It would appear that, unlike cimetidine, ranitidine does not interact pharmacokinetically with pethidine. Further studies are necessary to evaluate the potential clinical advantages of ranitidine vs cimetidine therapy in patients also receiving pethidine. PMID- 4027135 TI - Lack of effect of highly purified subunit influenza vaccination on theophylline metabolism. AB - Plasma concentrations of theophylline, and urinary recovery of theophylline and its metabolites [1, 3-dimethyluric acid, 3-methyl xanthine and 1-methyluric acid] were measured before and after highly purified subunit influenza vaccination in seven healthy subjects, and five subjects with chronic obstructive bronchitis. No cases of theophylline toxicity were seen, and there was no increase in mean plasma theophylline concentration or significant decrease in urinary metabolite concentration after vaccination. An antibody response to vaccination was demonstrated in all subjects. Highly purified subunit influenza vaccination may be given with safety to patients on theophylline. PMID- 4027137 TI - Caffeine disposition in obesity. AB - Caffeine pharmacokinetics were studied in 16 obese (mean +/- s.e. mean body weight; 110 +/- 8 kg; % ideal body weight (IBW); 186 +/- 14%) and 23 normal body weight (64 +/- 3 kg; 103 +/- 3% IBW) subjects. Eight obese and four control subjects were cigarette smokers. After abstaining from caffeine for 48 h and an overnight fast, each subject ingested 162 mg caffeine orally. Concentrations of caffeine were measured in plasma samples obtained during the 24 h following the dose and pharmacokinetic variables were determined. The apparent volume of distribution was increased markedly in obese subjects (69.9 +/- 5.9 vs 43.6 +/- 2.8 l; P less than 0.001) in the absence of any change in oral clearance (135 +/- 14-obese vs 112 +/- 12 ml/min; NS), resulting in a trend toward increased elimination half-life (7.05 +/- 1.08-obese vs 5.40 +/- 0.40 h; NS). Apparent volume of distribution correlated well with percent IBW (r = 0.65; P less than 0.001). Caffeine clearance, suggested as a measure of in vivo cytochrome P-448 activity in humans, was not altered in obesity. In contrast, the extent of caffeine distribution increased in direct relation to body weight. If caffeine is used therapeutically, the loading dose should be calculated as a function of total body weight. Since clearance of caffeine is not related to body weight, these data indicate that a chronic dosing regimen to maintain a given plasma caffeine concentration should not be altered due to obesity. PMID- 4027138 TI - Phenacetin O-deethylase: an activity of a cytochrome P-450 showing genetic linkage with that catalysing the 4-hydroxylation of debrisoquine? AB - Phenacetin O-deethylase activity was impaired, both in vivo and in vitro, in poor metabolisers of debrisoquine, consistent with the work of others. No impairment was observed in the oxidation of acetanilide, amylobarbitone or antipyrine in the PM phenotype. There was a good correlation (r = 0.804) between the high affinity component of phenacetin O-deethylase and debrisoquine 4-hydroxylase activities. No such correlation was observed with the low affinity component of phenacetin O deethylase activity. Although debrisoquine was a competitive inhibitor of phenacetin O-deethylase activity, phenacetin was without effect on debrisoquine 4 hydroxylation. There was also marked differences in the effects of sparteine, guanoxan and alpha-naphthoflavone on the two activities. Cigarette smoking was associated with a significant, two-fold, increase in phenacetin O-deethylase activity whilst debrisoquine 4-hydroxylase activity was not affected. It is concluded that the high affinity component of phenacetin O-deethylase and debrisoquine 4-hydroxylase activities are catalysed by different isozymes of cytochrome P-450 but that these are most probably regulated by closely linked genes. PMID- 4027139 TI - The metabolism of 7-ethoxycoumarin in human liver microsomes and the effect of primary biliary cirrhosis: implications for studies of drug metabolism in liver disease. AB - Using 7-ethoxycoumarin as a probe substrate, microsomal monoxygenase activity has been measured in liver tissue from patients with primary biliary cirrhosis (PBC) of varying histological severity, and in histologically normal control tissue. Interindividual variation in enzyme activity was considerable, and in no histological category was the activity significantly different to control. We conclude that: (a) in PBC, hepatic microsomal monoxygenase activity is determined primarily by factors other than the histological severity of the liver disease, and (b) studies of xenobiotic metabolism in patients with liver disease should specify the nature of the underlying disease process. PMID- 4027141 TI - pH lability in serum during equilibrium dialysis. AB - Changes in pH were determined in previously frozen normal human serum during dialysis against sodium phosphate, Krebs Ringer phosphate or Krebs Ringer bicarbonate buffers of pH 7.4. Serum was either untreated (native) or adjusted to pH 7.4 before dialysis. pH in native serum was 7.7-7.9 before dialysis, showed a decrease after 1 h, and an increase after 3 h. pH-adjusted serum showed a continuous pH increase during dialysis. The increase in serum pH during dialysis was larger at 37 degrees C than at 22 degrees C, larger at low than at high buffer molarity, and larger in native than in pH-adjusted serum. The observed changes in serum pH during dialysis are associated with unacceptably large errors in unbound fraction in serum for a number of important drugs. Drug binding determination in serum by equilibrium dialysis should be performed with buffers providing appropriate and stable pH level. PMID- 4027140 TI - Discovery of altered pharmacokinetics of CGP 15 210 G in poor hydroxylators of debrisoquine during early drug development. AB - The pharmacokinetics of CGP 15 210 G, a new 5-HT uptake inhibitor in poor and extensive metabolisers of debrisoquine, give indirect evidence of an association between its metabolism and polymorphic hydroxylation of the debrisoquine type. PMID- 4027142 TI - Slow release choline theophyllinate (Sabidal SR 270) in chronic asthma. PMID- 4027143 TI - Proceedings of the First International Symposium on Nicardipine. Brussels, Belgium, September 1984. PMID- 4027144 TI - The effect of acute and chronic nicardipine therapy on forearm arterial haemodynamics in essential hypertension. AB - By using simultaneous recording curves obtained with pulsed Doppler velocimetry and strain gauge mechanography, forearm arterial haemodynamics were studied in 26 patients with mild to moderate essential hypertension. Fifteen patients received a single oral dose of nicardipine 40 mg, and 11 patients were treated with nicardipine 30 mg three times daily for 3 months. In both groups of patients there was a similar and significant (P less than 0.001) reduction in mean, systolic, and diastolic pressures. There was a slight increase in heart rate (P less than 0.05) after the single dose, but no change after 3 months of treatment. The diameter, blood velocity, and blood flow of the brachial artery increased significantly in both treatment groups. The decrease in forearm vascular resistance was significant for both treatment groups. Brachial artery compliance increased (P less than 0.01) and characteristic impedance decreased (P less than 0.01) after both single-dose and long-term therapy with nicardipine. In patients who received nicardipine for 3 months, there were close correlations between the baseline serum calcium level and the percent change in vascular resistance (r = 0.73, P less than 0.01), blood flow (r = 0.89, P less than 0.001), and blood velocity (r = 0.91. P less than 0.001) of the forearm. No correlation was found between the baseline serum calcium and the change in arterial pressure. This study provided evidence that the blood-pressure-lowering effect of nicardipine was accompanied by a direct vasodilatory action in the small and large arteries of the forearm. An increase in peripheral blood flow with concomitant improvement of arterial compliance are the consequences of these arterial actions. PMID- 4027145 TI - The effect of nicardipine on blood pressure, its variability and reflex cardiac control. AB - Eight untreated patients with essential hypertension (average casual blood pressure 180/110 +/- 27/12 mm Hg) were studied following control, acute (a single oral dose of 30 mg nicardipine hydrochloride), and chronic (2 months nicardipine oral therapy) treatment periods. During the 2 month treatment period, ambulatory mean intra-arterial (IABP), measured when the patients were awake, fell from 165/105 +/- 6/12 (control) to 150/96 +/- 14/12 mm Hg (P less than 0.05), but heart rate remained unchanged (84 +/- 12 control vs 80 +/- 9 beats min-1). There was an absolute reduction in blood pressure in response to tilting, the Valsalva manoeuvre, and exercise handgrip, but the percent increase in pressure following nicardipine was not significantly different from that in the control period. There was no change in baroreflex sensitivity after either acute or chronic treatment, but the set point of the reflex was reset to a lower pressure following chronic therapy. Both single and multiple doses of nicardipine significantly reduced intra-arterial pressure. Chronic therapy was associated with return of the heart rate to control values, which was due to resetting of the baroreflex control mechanism. PMID- 4027146 TI - Blood pressure, heart rate and A-V conduction responses to nicardipine in hypertensive patients receiving atenolol. AB - The antihypertensive effect of the combined use of the new calcium channel blocker nicardipine and atenolol was assessed in a double-blind, placebo controlled trial involving twenty hypertensive patients. Atenolol 100 mg once daily was given to all patients. In addition, either placebo or nicardipine, in increasing doses (5-20 mg three times daily), was allocated randomly to the patients. Compared with placebo, nicardipine had an additional dose-dependent, blood-pressure-lowering effect in the hypertensive patients who had been pretreated with atenolol. An increase in the heart rate was not observed, suggesting that atenolol prevented reflex activation of sympathetic nerve tone caused by the vasodilating properties of nicardipine. The combination of both atenolol and nicardipine was well tolerated by all patients; side effects were minor and did not cause discontinuation of the treatment. No effects on A-V conduction were observed. It is concluded that the combined administration of nicardipine and atenolol is a useful treatment for hypertension that is well accepted by the patients. PMID- 4027147 TI - Immediate and long-term effects of nicardipine, at rest and during exercise, in patients with coronary artery disease. AB - Haemodynamic effects of nicardipine were studied in 12 patients with documented coronary artery disease. Following nicardipine 10 mg, given intravenously to patients at rest, the heart rate increased, mean arterial pressure decreased, cardiac index increased, and systemic vascular resistance decreased significantly. Compared with the control exercise values, significant increases in heart rate and cardiac index and significant decreases in mean arterial pressure, systemic vascular resistance, and left ventricular end diastolic pressure occurred when nicardipine, 10 mg i.v., was given to the patients during exercise. All 12 patients complained of angina during the exercise phase, but following treatment with nicardipine, 10 mg i.v., only four patients reported angina when exercising to the same level. Exercise capacity on oral nicardipine treatment tended to increase whilst the ejection fraction response to exercise did not change. Thus, nicardipine was a potent vasodilator, which produced a marked reduction of systemic vascular resistance and left ventricular end diastolic pressure during exercise. PMID- 4027148 TI - The acute haemodynamic effects of oral nicardipine. AB - The haemodynamic effects of oral nicardipine at two different doses were assessed in fifteen patients at rest following diagnostic cardiac catheterisation. Six patients received four doses of 20 mg nicardipine hydrochloride orally every 8 h, and nine patients received four doses of 30 mg orally every 8 h. No side effects were encountered with either dose. At both dose levels, there was a significant fall in systemic vascular resistance, significant increases in heart rate and cardiac output, and no change in stroke volume index. No changes were seen in pulmonary vascular haemodynamics, and there were no significant changes in mean arterial pressure. Plasma levels of nicardipine reached a peak within 1 h. In parallel with the haemodynamic effects, the plasma concentrations achieved after the third and fourth doses were higher than after the first dose. These haemodynamic changes are consistent with a vasodilator effect, which produces a decrease in peripheral vascular resistance. It would appear that the 30 mg dose has a more potent vasodilator action than the 20 mg dose and, in the patients studied, this larger dose was not associated with any side effects. PMID- 4027149 TI - The metabolism and pharmacokinetics of nicardipine hydrochloride in man. AB - Studies have been carried out to investigate the disposition of nicardipine hydrochloride following intravenous and oral administration to male volunteers. Following oral administration of a radiolabelled dose, nicardipine was shown to be rapidly and extensively metabolised and to be rapidly eliminated from plasma. After intravenous infusion of nicardipine at 5 mg-1 for 3 h, plasma levels declined biexponentially, and clearance values were of the same order as hepatic blood flow. With repeated oral administration, 20 mg three times daily for 28 days, plasma levels rose over the first 3 days of administration and then declined to some extent. Possible reasons for this decline are discussed. Steady state plasma levels and bioavailability show a nonlinear relationship with doses over the range 10-40 mg three times daily. Food consumption has been shown to reduce the bioavailability of nicardipine when the food is taken before or at the same time as nicardipine administration. PMID- 4027151 TI - Noninvasive assessment of the haemodynamic effects of nicardipine in normotensive subjects. AB - Calcium antagonists reduce myocardial contractility in vitro. Nicardipine is a dihydropyridine derivative with enhanced selectivity for vascular smooth muscle. We have studied the pharmacokinetics and the haemodynamic effects that occur in man following bolus intravenous administration of nicardipine. Ten normotensive male subjects received either nicardipine or placebo i.v., allocated in a randomised double-blind manner, over 60s. Plasma nicardipine concentration, blood pressure, heart rate, and systolic time intervals were measured before dosing and at frequent intervals between 1 and 360 min post dosing. At 160 micrograms kg-1, adequate plasma levels of nicardipine were obtained to permit analysis of individual pharmacokinetic variables, and significant and consistent haemodynamic effects were seen. After injection of nicardipine, systolic BP and the QS2 (measure of total electromechanical systole) and QT intervals were not altered. The changes in BP and heart rate were consistent with arteriolar vasodilatation. The changes in PEP and LVET suggest an increase in cardiac contractility, which is unlikely to be a direct effect of nicardipine on the myocardium but rather a result of afterload reduction. The close correlation of nicardipine plasma level with haemodynamic effect should permit accurate dose titration. The net increase in contractility should allow nicardipine to be administered safely with beta adrenoceptor blocking drugs. PMID- 4027150 TI - Nicardipine in models of myocardial infarction. AB - In a dog model of partial myocardial ischaemia, superimposed ST segment elevations in epicardial ECGs were inhibited by nicardipine over a cumulative i.v. dose range of 1-20 micrograms kg-1. Over the cumulative i.v. dose range of 0.5-166.5 micrograms kg-1, nicardipine had little overall effect on gross cardiac conduction, at spontaneous heart rate. Dogs that received oral 1-2 mg kg-1 nicardipine daily for 16 weeks and then survived 1 week occlusion of the left anterior descending coronary artery (LAD) developed a superior coronary collateral circulation compared with untreated animals. Nicardipine given by three different dosing schedules to baboons markedly limited myocardial infarction over a 6 h period of LAD occlusion. Compared with a group of completely untreated dogs, there was protection of the myocardium in the animals given nicardipine that survived 3 months occlusion of the LAD. PMID- 4027152 TI - Intracranial effects of nicardipine. AB - Preliminary investigations indicated that the calcium antagonist nicardipine improved cerebral vascular circulation and cerebral metabolism. Therefore we examined the effect of nicardipine on the cerebral vessels, cerebral oxygen tension, and intracranial pressure (ICP) in patients with cerebrovascular disturbances. In patients with previous minor stroke undergoing surgery for extra intracranial anastomosis, we applied nicardipine topically to the operation site by means of a perfusor and measured the diameter of the cerebral vessels. After several minutes, the topically applied nicardipine produced marked dilatation in the small arterial cortical vessels and relaxation of vasospasm. In the two patients studied so far, we observed a rapid increase in the cerebral PO2, which remained elevated after the initial peak as long as the infusion continued. With a lower dose the increase in the intracranial pulse amplitude (PAICP) was antagonized by the considerable drop in blood pressure which occurred after 10 mg h-1 nicardipine. The results indicate that nicardipine dilates the cerebral vessels and increases the cerebral oxygen tension. PMID- 4027154 TI - A micro-computer based system for surgical audit. PMID- 4027155 TI - Inversion injuries to the lateral ligament of the ankle joint. A pilot study of treatment. PMID- 4027153 TI - Cardiovascular pharmacology of nicardipine in animals. AB - The haemodynamic, antianginal and antihypertensive effects of nicardipine, a vascular selective calcium antagonist, were studied in experimental animals. In the canine isolated coronary artery, nicardipine relaxed potassium-induced contraction and suppressed 3,4-diaminopyridine-induced rhythmic contractions more effectively than nifedipine, verapamil or diltiazem. In anaesthetised rats, nicardipine prevented the elevation of ST segment induced by intracoronary injection of methacholine. In anaesthetised dogs, nicardipine produced a greater vasodilatation in vertebral, carotid, and coronary vessels than in mesenteric, femoral, and renal vessels and did not affect myocardial oxygen consumption. In conscious monkeys, nicardipine given intravenously lowered blood pressure and gave rise to reflex tachycardia but did not prolong the A-V conduction time. Nicardipine given orally lowered blood pressure in spontaneously hypertensive rats (SHR), renal hypertensive rats (RHR), and deoxycorticosterone acetate/salt hypertensive rats (DOCA/Salt), as well as in normotensive rats. Long-term treatment with nicardipine given orally for 12 weeks effectively lowered high blood pressure in the three types of hypertensive rats, reduced cardiac hypertrophy in SHR and DOCA/Salt rats, and prevented mortality from stroke in DOCA/Salt rats. Combined treatment with nicardipine and a beta-adrenoceptor blocking agent (indenolol) showed an antihypertensive effect similar to that obtained with nicardipine alone. Conscious renal hypertensive dogs given repeated oral administration of nicardipine for 14 days did not develop tolerance to the hypotensive activity of nicardipine. Under the same conditions, tolerance to hydralazine developed within 4 days. PMID- 4027156 TI - Haemarthrosis due to ascorbic acid deficiency. PMID- 4027157 TI - 'Alcohol-antabuse' syndrome in patients receiving metronidazole during gynaecological treatment. PMID- 4027158 TI - Erythema multiforme due to mianserin--a case against generic prescribing. PMID- 4027159 TI - Primary billiary cirrhosis in the elderly. PMID- 4027160 TI - Detection of the c-myc oncogene product in testicular cancer. AB - A set of monoclonal antibodies was constructed by immunising mice with peptide fragments of the c-myc oncogene product. One such antibody, Myc 1-6E10 was shown to bind to a 62,000 dalton protein identifiable with the c-myc product (p62c myc). The antigen recognised was not destroyed by paraffin wax embedding. Myc 1 6E10 was used to characterise the distribution of p62c-myc in archival testicular tumour material. Normal testes expressed only small amounts of p62c-myc. Seminomas showed increased nuclear and cytoplasmic staining. Undifferentiated teratoma showed little activity, whereas p62c-myc was abundant in the nuclei of differentiating epithelial structures, yolk sacs and embryoid bodies. Only small amounts of p62c-myc were seen in the tumours of 5 patients who subsequently died from their disease. PMID- 4027162 TI - The estimation of self-renewal in the clonogenic cells of human solid tumours: a comparison of secondary plating efficiency and colony size. AB - The in vitro clonogenicity of 25 human tumours was compared in two simple two layer culture systems, agar/agar and liquid medium/agar. There was a strong correlation between the values for clonogenicity obtained in each system. A linear relationship between cells plated and colonies formed was found in both systems. Radiation survival in the liquid culture system was essentially log linear with a small initial shoulder confirming that we were not simply counting clumps. We present a simple method of assessing the self-renewal capability of the clonogenic cells of human solid tumours, based on the liquid/agar two-layer system, which we have used to compare secondary plating efficiency and colony size analysis as measures of self renewal in human transitional cell carcinoma of the bladder. PMID- 4027161 TI - Reevaluation of alkaline phosphatase measurement during Hodgkin's disease by electrophoretic isoenzyme separation. AB - Electrophoretic isoenzyme separation provides much more precise information than measurement of alkaline phosphatases (AP). Use of this technique for 83 patients with Hodgkin's disease revealed that the presence of the alpha 1 fraction (alpha 1 AP) was very significantly correlated with the stage of disease extension (P less than 0.01) and above all with the presence of general symptoms (P less than 0.001). Repeat measurements performed during patient follow-up demonstrated a close association between presence of alpha 1 AP and existence of progressive disease. While the mechanism of appearance of this abnormal alpha 1 AP fraction is not linked to Hodgkin-specific liver lesions, this test provides much more interesting data than classical measurement of total alkaline phosphatases (TAP). PMID- 4027163 TI - The human tumour cloning assay in the management of breast cancer patients. AB - A tumour cloning system was used to cultivate breast cancer specimens. Fifty-six percent of 87 samples were adequate for evaluation, showing clonal growth in about one third (35%). Effusions yielded significantly better growth than solid specimens, the median colony numbers being 64 and 18 respectively. An attempt was made to examine whether there was any association between parameters accepted as prognostic factors for breast cancer and clonal growth in vitro. No correlation was found between preoperative tumour burden, histopathologic grading, menopausal status or overall survival and clonal growth in vitro, whereas we observed an inverse trend between progesterone receptor content of the tumours and their growth potential (P less than 0.01). In those few cases where in vitro and in vivo data could be compared, a high accuracy of the predicted sensitivities was found with respect to chemotherapy, but not in relation to hormonal treatment. A statistically significant higher overall chemosensitivity was associated with the absence of oestrogen receptors (P less than 0.01). PMID- 4027164 TI - Measurement of human tumour cell growth in soft-agar cultures using computer assisted volume analysis. AB - Growth in soft-agar bilayer cultures of human tumour cells derived from 4 in vitro continuous cell lines, from 21 xenografts carried in athymic mice, and from 197 samples of fresh human solid tumours of various histologic types was analyzed by computer-assisted image analysis. Replicate cultures for each specimen were assessed on successive days of incubation for the number and volume of growth units within multiple size categories. Our results confirm the recent finding of others that there is an upper limit of approximately 10(9) microns 3 to the cumulative growth unit volume obtainable in a 2 ml bilayer soft agar culture system. Since this upper limit to the carrying capacity of the closed culture system exists, the extent of growth within the cultures is determined in a fundamental way by the cumulative volume of growth units initially inoculated into cultures. A growth index of greater than or equal to 16-fold was only seen when initial cumulative growth unit volume was less than 10(7) microns 3 per culture dish. Computer-assisted volume analysis (CAVA) appears to be a useful quantitative method to study the growth of human tumour cells in soft agar cultures. PMID- 4027165 TI - The effect of passage in vitro and in vivo on the properties of murine fibrosarcomas. II. Sensitivity to cell-mediated cytotoxicity in vitro. AB - The sensitivity of cultured and mouse-passaged cloned lines of chemically-induced murine fibrosarcomas to killing by NK and NC cells, and to cell-mediated immunity, has been studied in in vitro assays, using target cells labelled with 51Cr or 125IUDR. None of the lines tested proved sensitive to NK cells. Three cultured lines were, at most, only slightly sensitive to NC cells; a fourth cultured line was moderately sensitive and became less so, but not completely insensitive, after passage in susceptible hosts. The primary object of these experiments was to test the hypothesis that cultured cell lines which ordinarily fail to grow in normal mice are able to grow after being passaged in a susceptible immunodeficient host because, during this passage, they become resistant to NK or NC cells. This has been shown to occur with one clone, but will not serve as a general explanation because, with other clones, both cultured and mouse-passaged lines were NC-insensitive. The cell-mediated immunity assays confirm our previous conclusion that cultured and mouse-passaged lines of the same clone differ little, if it all, in immunogenicity. PMID- 4027166 TI - Treatment of mouse carcinoma in vivo with a prostaglandin E2 analogue and indomethacin. AB - WHT/Ht mice transplanted s.c. with NC carcinoma were treated with 16,16-dimethyl prostaglandin E2 methyl ester (di-me-PGE2) and/or indomethacin. Each primary tumour was excised under anaesthesia 3 weeks after transplantation, weighed and extracted for prostaglandins. Mouse survival time and tumour recurrence were measured. Di-me-PGE2 10 micrograms, injected at the tumour site on alternate days from day 1 to 19, indomethacin 2.5 mg kg-1 daily by mouth, or both drugs together resulted in lighter tumours (respectively 45, 45 and 52% less, n = 18 to 20 per group, P less than 0.02) compared with vehicle-treated controls. Indomethacin reduced the tumour prostaglandin yield, but the biological activity in extracts of tumours from mice given di-me-PGE2 was high. The median survival time was longer in mice receiving indomethacin alone (61 days from tumour transplantation compared with 50 days in controls P less than 0.02). Di-me-PGE2 alone had little or no effect on survival (median 48 days) but counteracted the increase with indomethacin (di-me-PGE2 + indomethacin, 49 days median survival). There were no obvious effects of the treatments on tumour recurrence at the excision site, but there was a higher incidence of involved lymph nodes in mice given di-me-PGE2. PMID- 4027167 TI - The effects of pretreatment of human tumour cells with MNNG on the DNA crosslinking and cytotoxicity of mitozolomide. AB - Mitozolomide and its decomposition product MCTIC were found to be more cytotoxic to BE colon carcinoma cells in vitro than to HT-29 cells, another colon carcinoma cell line. In addition mitozolomide and MCTIC induced DNA interstrand crosslinks in the BE but not the HT-29 cell line. BE cells are deficient in the repair of O6 methylguanine lesions and are designated Mer-, whereas, HT-29 cells are proficient in this repair process and are designated Mer+. Thus DNA interstrand crosslinking produced by mitozolomide and MCTIC appears to correlate with the Mer phenotype. Pretreatment of HT-29 cells (Mer+) with the DNA methylating agent MNNG allows mitozolomide or MCTIC to produce DNA interstrand crosslinks. HT-29 cells also become more sensitive to the cell killing of mitozolomide and MCTIC with MNNG pretreatment. Pretreatment of Mer- cells (BE) had little effect on either cell killing or DNA crosslinking levels induced by mitozolomide or MCTIC. DNA interstrand crosslinking induced by mitozolomide and MCTIC is probably a consequence of an initial alkylation at the O6-position of guanine followed by a delayed reaction with the opposite DNA strand. PMID- 4027169 TI - Pancreatic carcinoma and hereditary nonpolyposis colorectal cancer: a family study. PMID- 4027168 TI - A follow-up study of cancer incidence among workers in manufacture of phenoxy herbicides in Denmark. AB - The purpose of this cohort study is to shed further light on the potential carcinogenic effect indicated by a Swedish case control study of the 2,4 dichlorophenol and 4-chloro-ortho-cresol based phenoxy herbicides, unlikely to be contaminated with 2,3,7,8-tetrachlorodibenzo-p-dioxin (2,3,7,8-TCDD). In the present study it was the intention to include all persons employed in manufacture of phenoxy herbicides in Denmark before 1982. The predominant product was MCPA and only a very limited amount of 2,4,5-T was processed in one of the two factories included in the study. Registration of the cohort was based on company records, supplemented with data from a public pension scheme from 1964 onwards. Ninety-nine percent of registered employees could be followed up. Cancer cases were identified by linkage with the National Cancer Register. Totals of 3,390 males and 1,069 females were included in the study. In the analysis special attention was given to soft tissue sarcomas (STS) and malignant lymphomas (ML) which are the diagnostic groups indicated to be associated with exposure to phenoxy herbicides in the Swedish studies. Five cases of STS were observed among male employees in contrast to 1.84 expected cases. This result supports the Swedish observation of an increased risk of STS following exposure to phenoxy herbicides unlikely to be contaminated with 2,3,7,8-TCDD. However, several potential biases have to be taken into account in interpretation of this observation and these are discussed. Seven cases of ML were observed among male employees in contrast to 5.37 expected which does not support the Swedish observation of an excess risk. The total cancer risk among persons employed in manufacture and packaging of phenoxy herbicides was equivalent to the cancer risk in the Danish population. Among males thus employed 11 lung cancer cases were observed in contrast to 5.33 expected. Attention should be given to exposure to spray dried MCPA-sodium salt in the plants, but other work place exposures and tobacco consumption may have contributed to the increased risk. The tabulation of data by many diagnostic groups may explain the excesses observed for rectum cancer among males and cervical cancer among females. The study has revealed that several potential biases have to be taken into account when the Swedish observations are tested in other settings. PMID- 4027170 TI - Stage of colorectal carcinoma and rate of blood loss. PMID- 4027171 TI - Social behaviour of hearing-impaired and normally-hearing preschoolers. PMID- 4027172 TI - Taking control of stress in teaching. PMID- 4027173 TI - Rapid induction of cirrhosis by administration of carbon tetrachloride plus phospholipase D. AB - A new and rapid method for the production of liver cirrhosis in the rat is described. Rats were treated with carbon tetrachloride for 4 weeks and then injected i.p. with phospholipase D daily for 6 days. Controls received either carbon tetrachloride or phospholipase D only. Following the combined treatment cirrhosis developed rapidly; the liver developed micronodules and severe cirrhosis was accompanied by ascites and splenomegaly. PMID- 4027174 TI - Effect of hypoxia and carbon monoxide on collagen synthesis in cultured porcine and bovine aortic endothelium. AB - The cell layers and medium of cultured porcine and bovine aortic endothelium have been examined to test the effects of 24 h treatment with two factors associated with cigarette smoke--hypoxia and carbon monoxide, on cell numbers, total protein including collagen/10(6) cells, collagen type profile and ultrastructure. The most significant findings were that the responses varied with the species and that the effects on protein synthesis including collagen differed depending on the nature of the insult; in general, moreover carbon monoxide tended to reverse the action of hypoxia, a finding supported by ultrastructural evidence. The phenotypic collagen profiles were unaffected by either hypoxia or carbon monoxide. PMID- 4027175 TI - Acute upper genital-tract disease in female monkeys provoked experimentally by Mycoplasma genitalium. AB - The oviducts of two grivet monkeys and three marmosets, all sexually mature animals, were inoculated with Mycoplasma genitalium at laparotomy. The mycoplasma was not recovered from the grivet monkeys, nor from the oviducts of the marmosets although it was isolated intermittently from the vagina of two of the latter animals up to 4-6 weeks after inoculation. In contrast, all of the animals developed antibody to M. genitalium measured by a micro-immunofluorescence technique. It developed rapidly in the grivet monkeys but slowly in the marmosets, being detected first about 1 month after inoculation with a maximal response by 2 months. Furthermore, despite an absence of vaginal discharge or cytological response, all the animals developed a moderate to severe endosalpingitis characterized by the infiltration of acute inflammatory cells into the tubal epithelium, together with a lumenal exudate and adhesions between the mucosal folds. The changes are similar to those produced by Chlamydia trachomatis in simian models and naturally in women. PMID- 4027176 TI - Effect on Chlamydia trachomatis infection of the murine genital tract of adoptive transfer of congenic immune cells or specific antibody. AB - Groups of progesterone-treated female CBA/nu mice were adoptively transferred with immune spleen cells or pooled antisera from congenic immunocompetent CBA donors that had been infected with a 'fast', human strain (SA-2f) of Chlamydia trachomatis. The spleen cells were given either intravenously (6.3 X 10(7) cells) or intraperitoneally (9.5 X 10(7) cells), and the antiserum (antibody titre 1:4096) was given intravenously. Strain SA-2f was introduced into the uterine cavity of these mice approximately 3 h after cell or antiserum transfer; antiserum was given also at intervals up to 23 days later. Untreated mice serving as controls were inoculated with chlamydiae in the same way. Subsequent recovery of chlamydiae from mice in the various groups indicated that transfer of cells or antiserum had not abrogated the chlamydial infections, despite high titres of chlamydial IgG antibody in the sera of all the recipient mice. These results confirm our earlier findings but are unlike those of some other investigators working with different mouse model systems. It seems that there are differences between systemic/respiratory immune mechanisms and those which operate locally in the uterus, which may be regarded as an immunologically privileged site. PMID- 4027177 TI - Studies into the influence of carrageenan-induced inflammation on articular cartilage degradation using implantation into air pouches. AB - We describe a novel system for examining the degradation of articular cartilage in vivo. Implantation of rat femoral head cartilage into six day old subcutaneous air pouches allows the examination of the degradation of cartilage in contact with a synovial lining-like structure. Femoral head cartilage was removed 1, 2 or 3 weeks after implantation and the proteoglycan content measured using 1,9 dimethyl methylene blue. Chondrocyte viability was confirmed using 35S sulphate incorporation. Increasing proteoglycan loss was observed over 3 weeks. Loss was similar in transplants between inbred and between outbred animals, suggesting that allograft rejection did not contribute significantly. Introduction of the irritant carrageenan into pouches produced a massive and prolonged inflammatory response characterized by exudation of leucocyte-rich fluid. Induction of inflammation with carrageenan did not alter the profile of proteoglycan loss from whole, minced, live or dead cartilage, as compared to that seen in non-inflamed pouches. These results indicate that when the relationship between articular cartilage and its normal tissue surroundings is disturbed, rapid proteoglycan loss may occur. The conditions induced by carrageenan inflammation have, in comparison, little or no effect on cartilage degradation. This raises the possibility that the direct effects of inflammatory products are of relatively minor importance to cartilage destruction in human arthritis. PMID- 4027178 TI - The immune response to pertussis in the 6-day air pouch: a model of chronic synovitis. AB - We have developed a model of prolonged immunological inflammation in the rat which has a structural resemblance to the synovial changes in rheumatoid arthritis. Pertussis vaccine was injected into 6-day-old subcutaneous air pouches in animals previously sensitized with pertussis vaccine. The resulting inflammatory response persisted up to 30 days. Examination of exudates showed a wave of polymorphonuclear leucocytes over a 13-day period followed by a mononuclear cell predominance up to 30 days. Histologically, an early polymorphonuclear cell infiltration was followed by the formation of a lining layer of large eosinophilic mononuclear cells, together with deep collections of lymphocytes and plasma cells. Concentrations of the acute-phase reactant alpha 1 glycoprotein, in both serum and exudate, peaked at 3 days. This suggests that the local production of interleukin I in this type of tissue reaction is more closely related to the acute inflammatory phase than to more chronic interactions between monocyte derived cells and lymphocytes. PMID- 4027179 TI - The role of platelets in mesangial localization: carbon uptake in thrombocytopenic rats. AB - The role of platelets in mesangial localization has been studied in Lewis rats following a single intravenous injection of colloidal carbon 32 mg/100 g body weight. Following carbon injection there was an abrupt thrombocytopenia (peripheral platelet count at 10 min 165 +/- 107 X 10(3)/mm3). Temporary sequestration of platelets in lung, liver and spleen was demonstrated using quinacrine-labelled platelets. Carbon was quantitated in blood, lung, liver and spleen by digestion and spectrophotometry and in glomerular mesangium by particle counting of histological sections under oil-immersion microscopy. In thrombocytopenic rats (busulphan 17.5 mg/kg weight) blood carbon levels (up to 1 h after injection) were higher than normal controls (P less than 0.01) and mesangial carbon content at 24 h was significantly increased (P less than 0.01). No significant alteration in mononuclear phagocytic function was detected at 24 h. In platelet-restored thrombocytopenic rats, (busulphan-treated, infused with homologous platelets) blood and mesangial carbon levels were decreased towards normal values. These findings show that (1) platelets are involved in the initial removal of carbon from the blood (2) mesangial localization is related to blood levels and (3) platelet numbers affect both these parameters. The finding of increased mesangial deposition in thrombocytopenic rats may have significance for immune complex glomerulonephritis where platelet numbers may be low due to persistent platelet activation. PMID- 4027180 TI - Detection of reticulo-endothelial blockade with low-dose test agent. AB - Blood clearance and organ extraction of a low-dose reticulo-endothelial test agent, technetium labelled tin colloid (TTC), was measured in groups of rabbits pretreated with reticulo-endothelial blocking agents. Electron microscopy and ultrastructure analysis confirmed that Kupffer cells extracted TTC. Pretreatment with silica caused reduced Kupffer cell uptake and spillover of TTC into the spleen. Pretreatment with sheep red cells caused reduced Kupffer cell uptake and reduced splenic uptake but anti-fibronectin caused only reduced splenic uptake of TTC. TTC is a suitable agent to detect alteration of reticulo-endothelial function. PMID- 4027181 TI - Lethal epidermolytic epidermolysis bullosa: a new autosomal recessive type of epidermolysis bullosa. AB - A distinctive form of epidermolysis bullosa is reported among several members of a large Sudanese family. Although on ultrastructural grounds this appears to be simplex type, it is inherited as an autosomal recessive trait and is associated with a high mortality. PMID- 4027182 TI - Vitiligo in diabetes mellitus. AB - We studied the association between vitiligo and diabetes mellitus, and found that vitiligo is associated with insulin-dependent diabetes but not with non-insulin dependent diabetes. This gives further weight to the theory that vitiligo is an autoimmune disease. PMID- 4027183 TI - PUVA therapy of chronic actinic dermatitis. AB - Four men with long-standing chronic actinic dermatitis were treated with a modified PUVA regime which initially included generalized applications of topical steroids given immediately after PUVA exposure. All patients are now free of rash, no longer need protection from UV radiation, and are being maintained on twice monthly PUVA therapy (IO J/cm2). PMID- 4027185 TI - The cutaneous reaction to staphylococcal protein A in normal subjects and patients with atopic dermatitis or psoriasis. AB - Intradermal testing with the staphylococcal cell wall component, protein A, in healthy volunteers and in patients with atopic dermatitis and psoriasis produced a range of responses but in all groups there was an immediate weal and flare response. There was marked individual variation in subsequent erythema, but the patients with atopic dermatitis had less erythema at 15 min and 24 h than normal or psoriatic individuals. The greatest erythematous reaction at 48 h was seen in patients with psoriasis. PMID- 4027184 TI - The number and distribution of benign pigmented moles (melanocytic naevi) in a healthy British population. AB - Total body mole counts have been performed on 432 normal healthy Caucasian subjects aged 4 days to 96 years (204 males and 228 females). The mean total body mole count in the first decade of life is three for females and two for males, rising rapidly in the second decade to a mean of 23 for females and 18 for males. In the third decade numbers are highest, with a mean of 33 for females and 22 for males. Thereafter, numbers of moles slowly drop until in the eighth decade they have fallen to levels similar to those seen in pre-pubertal children. There is a significant association between the presence of naevi in early childhood (prior to 5 years of age) and the development in later life of large numbers of moles. In women there is no significant association between total mole counts and either parity or use of the oral contraceptive. PMID- 4027186 TI - Stimulated mitotic counts in the non-lesional skin of patients with psoriasis and controls. AB - Mitotic counts have been determined in the symptomless skin of nine psoriatic patients and nine healthy controls 48 h after pressure-tape stripping. A significantly increased response was seen in the symptomless psoriatic epidermis compared with the controls. PMID- 4027187 TI - Spatial variability of vasodilatation in human forearm skin. AB - Vasodilatation elicited by topical application of methyl nicotinate was measured by photoplethysmography at various positions on human ventral forearm skin. The time-to-peak response, the magnitude of the peak response, the area under the response-time curve and the time for the response to decay to 75% of the maximum value, were recorded at six positions on the left and right forearms of eight subjects. There was no significant difference between response on the right and left forearm sites and no difference in response between the lateral and medial sites on the forearms. In a second experiment, the vasodilatation was measured at proximal and distal positions on the forearm. The magnitude of the peak response at the proximal position was significantly higher than that found distally (P less than 0.01) as was the area under the response-time curve (P less than 0.05). These results suggest a possible cause for the variation observed in vasoconstrictor assays of corticosteroids. PMID- 4027188 TI - Lectin binding to psoriatic epidermis. AB - The lectin-binding properties of psoriatic epidermis were assessed using a wide range of lectins. Changes in these properties were found at all levels of differentiation in lesional tissue. There was no clear evidence for an expansion in the population of basal-type cells. Binding of some lectins demonstrated a normal basal-suprabasal boundary. Others bound closer to the dermal-epidermal junction than in normal tissue, and expression of certain normal suprabasal characteristics was found in the basal layer in psoriasis. These findings suggest that the detected changes in psoriatic glycoconjugates reflect a programme of differentiation which is altered rather than incomplete. PMID- 4027189 TI - Ultraviolet radiation-induced histopathological changes in the skin of the marsupial Monodelphis domestica. I. The effects of acute and chronic exposures and of photoreactivation treatment. AB - Post-ultraviolet radiation (UVR) treatment of the South American opossum, Monodelphis domestica with long-wavelength radiation (320-400 nm) suppressed the induction of histopathological alterations in the skin. This study identifies DNA as a primary chromophore involved in the induction of various photobiological responses of the skin such as hyperplasia and sunburn cell formation, and also identified pyrimidine dimers as one responsible DNA lesion. The histology of skin from opossums exposed to multiple doses of UVR showed that pre-malignant changes had occurred in the skin. PMID- 4027190 TI - Effect of platelet homogenate on in vitro glycosaminoglycans production by dermal fibroblasts from systemic sclerosis patients and normal controls. AB - Confluent cultures of dermal fibroblasts from the involved skin of systemic sclerosis patients (SF) and a matched skin site of normal controls (NF) were investigated for the synthesis of glycosaminoglycans (GAG) in response to various concentrations of human platelet homogenate (PH). Experiments were carried out in the presence of 1% and 15% human serum (HS). In the absence of PH, GAG synthesis was higher in SF than NF. An increase in GAG synthesis was demonstrated in both SF and NF as the concentration of PH was increased to 200 micrograms/ml of growth medium. The PH-stimulated GAG synthesis occurred in 15% HS treated SF and NF, but there was no GAG synthesis increase in 1% HS-treated NF. The absolute count of GAG synthesis was always greater in SF than NF. The addition of PH in concentrations higher than 200 micrograms/ml led to cell death of both SF and NF. These findings are the first to indicate a difference between SF and NF response to PH. PMID- 4027191 TI - Short contact dithranol therapy--twice daily and high concentration regimes. PMID- 4027192 TI - Taping for embedded toenails. PMID- 4027193 TI - Deficient natural killer (NK) cells in paroxysmal nocturnal haemoglobinuria (PNH): studies of lymphoid cells fractionated by discontinuous density gradient centrifugation. AB - Non-adherent, non-B lymphoid cells from six patients with PNH and six healthy subjects were fractionated by Percoll discontinuous density gradient centrifugation (DDGC). The cell distribution pattern, NK cell activity (NKA), large granular lymphocytes (LGL) count and surface marker phenotypes were studied. The distribution patterns of patients' cells did not significantly differ from the controls. The peak of the NKA was found in low density fractions where the maximum counts of LGL, Leu-7+2- cells and Leu-11+ cells were present. The NKA and the proportion of Leu-7+2- cells and Leu-11+ cells were significantly lower in patients with PNH (P less than 0.001 for NKA and surface phenotypes; P less than 0.02 for LGL counts). NKA in the Percoll fractions was correlated with the counts of LGL (r=0.69, P less than 0.001), Leu-7+2- cells (r = 0.75, P less than 0.001) and Leu-11+ cells (r = 0.89, P less than 0.001). Therefore, we concluded that NKA is deficient in PNH because of decreased NK cell counts. PMID- 4027194 TI - Carrier detection in factor VII congenital deficiency. AB - Thirty obligate and 28 possible carriers of factor VII congenital deficiency, belonging to 16 families, were studied in relation to the immunological variants to which the kindreds belonged, namely, VII+, VIIR and VII-. Factor VII activity and antigen determinations in these subjects formed two phenotypical patterns: a discrepant pattern characterized by a low ratio activity/antigen present in VII+ heterozygotes, and a non-discrepant pattern (normal ratio activity/antigen) which is present in the VII- and VIIR variants. In the first genetic variant the detection of carriers can be performed using the ratio VII:C/VII:Ag. In the other variant, which accounts for the vast majority of heterozygotes, the distribution of the carriers' factor VII is so widespread that a large overlap results between these subjects and the normals. The application of a probabilistic calculation performed by combining the actual values of factor VII:C and the genetic probability of carriership using Fisher's linear discriminant analysis, makes discrimination between carriers and normals easier. PMID- 4027195 TI - Heterogeneity of erythropoietin-dependent erythrocytosis: case report in a child and synopsis of primary erythrocytosis syndromes. AB - To investigate the pathogenesis of polycythaemia in a child with isolated, primary erythrocytosis, we measured serum erythropoietin activity and in vitro erythroid progenitor cell responsiveness to erythropoietin. Unstimulated erythropoietin activity was markedly elevated (1.8 IU/ml), and isovolaemic phlebotomy induced a four-fold increment above this level. In contrast to findings in our index case with this syndrome, normal erythroid colony growth patterns were present in patient marrow cultures. The primary mechanism of polycythaemia in this individual is similar to that reported in the index case: an inappropriately elevated regulatory set point for erythropoietin production. Since an additional defect of progenitor cell hypersensitivity to erythropoietin is not always present, we conclude that abnormalities at single or multiple sites of the erythropoietic regulatory axis may occur in primary erythropoietin dependent erythrocytosis. PMID- 4027196 TI - Red cell kinetics in thalassaemia intermedia. PMID- 4027198 TI - Cytochemistry in the differential diagnosis of monoclonal gammopathies. PMID- 4027197 TI - Prolymphocytic leukemia treated by leukapheresis with relief of respiratory symptoms. PMID- 4027199 TI - Chronic lymphocytosis due to the expansion of granular lymphocytes. PMID- 4027200 TI - Debendox revisited. AB - Two further studies re-examine the findings by Golding et al. (1983) in Oxford that mothers of children born with oral clefts had been more frequently prescribed Debendox (Bendectin) than had the mothers of matched controls. In Cardiff, 86 283 total births between 1965 and 1979 included 139 infants with oral clefts. Detailed information was obtained about 93 of these infants and matched controls. The relative risk of the birth of an infant with an oral cleft to women prescribed Debendox within 69 days of the first day of their last menstrual period was 0.64 (95% confidence limits 0.12-3.34). No increased effect was found amongst women who smoked. In Aberdeen, 17 640 livebirths between 1976 and 1979 included 31 children with oral clefts. Compared with the non-exposed group the risk of a birth of an infant with an oral cleft to a woman prescribed Debendox in early pregnancy was 0.37 (95% confidence limits 0.09-1.47). These results do not confirm the previous findings in Oxford of a possible association between exposure to Debendox in early pregnancy and the occurrence of oral clefts in the child. PMID- 4027202 TI - Risks of midtrimester amniocentesis; assessment in 3000 pregnancies. AB - The obstetric outcome of 3000 pregnancies with midtrimester amniocentesis was followed in all but one patient. Thirty pregnancies ended in fetal death or abortion within 3 weeks after amniocentesis. Chronologically 23 of these occurred in the first series of 1500 pregnancies and the remaining seven fetal deaths/abortions within 3 weeks after amniocentesis occurred in the second series of 1500 pregnancies. Fetal loss within 3 weeks after amniocentesis was apparently related to the experience of the obstetrician and to the use of modern ultrasound guidance. It is concluded that the risk of fetal death after midtrimester amniocentesis is approximately 0.5%, if only experienced obstetricians using modern techniques are involved. PMID- 4027201 TI - Protein synthesis and secretion by the human endometrium and decidua during early pregnancy. AB - To investigate the role of the endometrium in sustaining early pregnancy, specimens of endometrium from early pregnancy were incubated in vitro with radiolabelled amino acids, and protein synthesis and secretion were studied by subsequent fluorographic analysis of one-and two-dimensional polyacrylamide gels. Seventeen secreted endometrial proteins (EP) were identified. Changes were demonstrated in the rate of synthesis and/or secretion of a number of these proteins during early pregnancy. Two proteins, EP 14 and EP 15, are the principal secretory proteins of pregnancy endometrium. EP 14 (subunit mol. wt 32 000) is associated with decidualized endometrium and its rate of synthesis/secretion increases during early pregnancy. EP 15 (subunit mol. wt 28 000) is also synthesized and secreted by the secretory endometrium during the menstrual cycle, and during early pregnancy, but its secretion declines to undetectable levels by week 15-16. These proteins may provide useful markers of endometrial function and differentiation during the menstrual cycle and pregnancy. PMID- 4027203 TI - Chorioamnionitis and funiculitis in the placentas of 200 births weighing less than 2.5 kg. AB - A retrospective histopathological study of the placental and non-placental membranes and umbilical cords of 200 live and stillborn babies weighing less than 2.5 kg is reported. The pathological studies were specifically concerned with the presence of infection as evidenced by a polymorphonuclear leucocytic infiltrate at these sites. Inflammatory lesions were demonstrated in 48.5% of specimens. The incidence of inflammatory lesions was highest in those with prolonged rupture of the membranes, and in the placentas of the smallest and least mature infants of a size appropriate to their gestational age. Puerperal pyrexia, neonatal sepsis and perinatal mortality were also more common in the infected group but none of the perinatal deaths was directly attributable to infection. The role of infection as a cause of premature rupture of the membranes, premature labour and subsequent perinatal outcome is still unclear though our data would suggest it is not unimportant. PMID- 4027204 TI - Episiotomy and third-degree tears. AB - The relation of episiotomy to third-degree perineal tears was investigated in 21 278 singleton deliveries. The incidence of episiotomy was 28.4% (n = 6041). Third degree tears occurred in 1.4% (85) of the deliveries with episiotomy and in 0.9% (132) of the deliveries without episiotomy (P less than 0.01). To avoid the effect of confounding factors, we analysed a sub-sample that included only vertex presentations with spontaneous occipitoanterior vaginal deliveries. After stratification for birthweight and parity, no relation between episiotomy and third-degree tear was found. PMID- 4027205 TI - Faecal incontinence due to external anal sphincter division in childbirth is associated with damage to the innervation of the pelvic floor musculature: a double pathology. AB - The commonest cause of external anal sphincter division is injury during childbirth. We have studied 20 patients with anterior external anal sphincter division using physical and electrophysiological techniques. There was evidence of pudendal nerve damage in 60% of these patients. This finding suggests that damage to the innervation of the external anal sphincter often co-exists with direct injury to the muscle; in these patients pelvic floor surgery may be required, in addition to sphincter repair itself. PMID- 4027206 TI - Uroflowmetry for predicting postoperative voiding difficulties in women with stress urinary incontinence. AB - Pre-operative knowledge of uroflowmetry and postvoiding residual urine volumes in a group of 45 women undergoing urinary incontinence surgery failed to predict risks of postoperative voiding difficulties. Only one out of nine patients needing prolonged post-operative bladder drainage (greater than or equal to 7 days) gave a pre-operative history of voiding difficulties. More than half the patients (5/9) who needed prolonged catheterization had normal flow rates were able to resume spontaneous voiding within 7 days following incontinence surgery. PMID- 4027207 TI - Age as a prognostic factor in epithelial ovarian carcinoma. AB - One prognostic factor in epithelial ovarian cancer appears to be the patient's age at presentation. We have retrospectively analysed data from 2305 patients with this tumour in East Anglia during the period 1960-1980. The influence of age as a factor in survival was studied by comparing outcome in young patients between the ages of 15 and 35 (3.1% of all cases) with the outcome in the women over 35. The prognosis was significantly better in young patients, even when age correction is applied. This has implications for the management of patients with this common tumour. PMID- 4027208 TI - Immunohistological characterization of antigen expression by trophoblast populations in ectopic cornual implantation. Case report. PMID- 4027209 TI - Transient blindness associated with pregnancy-induced hypertension. Case reports. PMID- 4027210 TI - Bilateral tubal ectopic pregnancy following in-vitro fertilization and embryo replacement. Case report. PMID- 4027211 TI - Placenta percreta causing uterine rupture. Case report. PMID- 4027212 TI - Leiomyomatosis peritonealis disseminata. A report of two cases and a review of the literature. PMID- 4027213 TI - Aggressive endometrial stromal sarcoma responding to medroxyprogesterone following failure of tamoxifen and combination chemotherapy. Case report. PMID- 4027214 TI - Zollinger-Ellison syndrome due to a gastrin secreting ovarian mucinous cystadenoma. Case report. PMID- 4027215 TI - Mechanism of inactivation of 3-oxosteroid delta 5-isomerase by 17 beta-oxiranes. AB - The affinity label (17S)-spiro[estra-1,3,5(10),6,8-pentaene-17,2'-oxiran]-3-ol (5 beta) inactivates 3-oxosteroid delta 5-isomerase from Pseudomonas testosteroni by formation of a covalent bond between Asp-38 of the enzyme and the steroid. High performance liquid chromatography (HPLC) analysis of tryptic digests of inactivated enzyme shows that two isomeric steroid-containing peptides are formed in a ratio of 9:1 at pH 7 (TPS1 and TPS2). Hydrolysis of each of these peptides produces a different steroid: TPS1 releases 17 alpha-(hydroxymethyl)estra 1,3,5(10),6,8-pentaene-3,17 beta-diol (S1) whereas TPS2 yields 17 beta (hydroxymethyl)estra-1,3,5(10),6,8-pentaene-3,17 alpha-diol (S2). Inactivation of the enzyme by (17S)-spiro[estra-1,3,5(10),6,8-pentaene-17,2'-oxiran-18O]-3-ol, followed by mass spectral analysis of the diacetate of the steroid released upon hydrolysis of the enzyme-inhibitor bond, reveals that TPS1 is formed by attack of Asp-38 at the methylene carbon of the oxirane. In contrast, TPS2 is produced by Asp-38 attack at the tertiary carbon. These results imply that inactivation occurs through concurrent SN1 and SN2 reactions of Asp-38 with the protonated inhibitor and that Asp-38 is located on the alpha face of the steroid when it is bound to the active site in the correct manner to react for both the SN1 and SN2 processes. PMID- 4027216 TI - Influence of hydrophobic and steric effects in the acyl group on acylation of alpha-chymotrypsin by N-acylimidazoles. AB - The second-order rate constants k2/Km for acylation of alpha-chymotrypsin by a series of N-acylimidazole derivatives of aliphatic carboxylic acids have been determined at 30 degrees C by proflavin displacement from the active site. With cyclohexyl-substituted N-acylimidazoles, the rate constants increase with increasing chain length of the acyl group; i.e., k2/Km is in the order cyclohexylcarbonyl less than cyclohexylacetyl less than beta-cyclohexylpropionyl. The latter substrate has k2/Km = 1.2 X 10(6) M-1 s-1 at pH 8.0, which appears to be a maximum value for N-acylimidazole substrates. A further increase in the chain length of the acyl group with (gamma-cyclohexylbutyryl)imidazole results in a decrease in k2/Km. Hydrophobic effects of the hydrocarbon acyl groups are of predominant importance with regard to the relative values of k2/Km for aliphatic N-acylimidazole substrates. There is a linear correlation of the logarithms of the rate constants at pH 8.0 with the hydrophobic substituent constants, pi, having a slope of 1.71 (r = 0.90). On the other hand, there is little apparent correlation with the Taft steric effect constants, Es. A four-parameter equation including both pi and Es improved the correlation only slightly [log (k2/Km) = 1.88 pi + 1.01 Es + C]. In contrast, steric effects as reflected in the Es constants are the major influence in acylation of the enzyme by corresponding p nitrophenyl esters. There are very likely significant differences in transition state structure with the two types of substrates. PMID- 4027217 TI - Effects of lipid environment on the light-induced conformational changes of rhodopsin. 1. Absence of metarhodopsin II production in dimyristoylphosphatidylcholine recombinant membranes. AB - Photolysis of bovine rhodopsin in dimyristoylphosphatidylcholine recombinant membranes results in the production of a relatively stable metarhodopsin I like photointermediate that decays slowly to a species with a broad absorbance maximum centered at about 380 nm [O'Brien, D. F., Costa, L. F., & Ott, R. A. (1977) Biochemistry 16, 1295-1303]. On the basis of the results of a variety of chemical and spectroscopic tests, we show that this process corresponds to the production of free retinal plus opsin and not to the slow production of metarhodopsin II. Electron spin resonance studies using a novel disulfide spin-label that is covalently linked to rhodopsin indicate that the apparent arrest of the protein at the metarhodopsin I stage is not due to simple aggregation of the protein in this short-chain, saturated lipid bilayer but must be understood in terms of the effect of the lipid host on the conformational energies of individual protein molecules. Limited production of metarhodopsin II is observed under acidic conditions. Thus, the rhodopsin-dimyristoylphosphatidylcholine recombinants offer a unique system for the study of the effect of the phospholipid bilayer environment on the conformation of an intrinsic membrane protein. PMID- 4027218 TI - Effects of lipid environment on the light-induced conformational changes of rhodopsin. 2. Roles of lipid chain length, unsaturation, and phase state. AB - When rhodopsin is incorporated into the saturated short-chain phospholipid dimyristoylphosphatidylcholine, photolysis of the protein results in an abnormal sequence of spectral transitions, and the dominant product of metarhodopsin I decay is free retinal plus opsin [Baldwin, P. A., & Hubbell, W. L. (1985) Biochemistry (preceding paper in this issue)]. By incorporation of rhodopsin into a series of phosphatidylcholines of defined composition, we have determined the properties of the lipid environment that are responsible for the altered spectral behavior. Metarhodopsin II is not found in appreciable amounts in bilayers containing acyl chains that are too short (14 or fewer carbon atoms in length), in the presence of only n-alkyl chains, or below the characteristic phase transition temperature of recombinant membranes. Double bonds are not required for the formation of the metarhodopsin II intermediate, as it is observed in diphytanoylphosphatidylcholine recombinants. PMID- 4027219 TI - Nanosecond optical spectra of iron-cobalt hybrid hemoglobins: geminate recombination, conformational changes, and intersubunit communication. AB - Hybrid hemoglobins were prepared in which cobalt was substituted for the heme iron in either the alpha or beta subunits. Transient optical absorption spectra were measured at room temperature for these hybrids at time intervals between 0 and 50 ms following photodissociation of the carbon monoxide complex with 10-ns laser pulses. The cobalt porphyrins do not bind carbon monoxide, making it possible to investigate the time-resolved response of the cobalt-containing subunits to photodissociation of carbon monoxide in the iron-containing subunits. At the same time the response of the iron-containing subunits to the photolysis event can be studied, permitting an independent determination of the kinetics of ligand rebinding and conformational changes in the alpha and beta subunits of an intact tetramer. The data were analyzed by using singular-value decomposition to obtain the kinetic progress curve for ligand rebinding, the deoxyheme and cobalt porphyrin spectral changes, and the time course of these spectral changes. The geminate rebinding kinetics following photodissociation of alpha(Co)2 beta(Fe CO)2 were very similar to those found unsubstituted hemoglobin, alpha(Fe-CO)2 beta(Fe-CO)2, indicating equivalence of the geminate kinetics for alpha and beta subunits within the R-state tetramer. The results for alpha(Fe-CO)2 beta(Co)2 were consistent with this conclusion, even though the analysis was complicated by the presence of comparable populations of R- and T-state species. Comparison of the deoxyheme spectral changes and relaxation times among the three molecules indicated that both alpha and beta subunits contribute to the deoxyheme spectral changes that signal tertiary and quaternary conformational changes in the unsubstituted tetramer. The response of the cobalt porphyrins to photodissociation was similar in the two hybrids. No structural changes were detected in the cobalt-containing subunits until the second tertiary conformational change in the iron-containing subunits observed at 1-2 microseconds. Much larger structural changes, as judged by the amplitude of the spectral changes, occurred in the cobalt-containing subunits concomitant with the R----T quaternary change at about 20 microseconds. PMID- 4027220 TI - Influence of an extrinsic cross-link on the folding pathway of ribonuclease A. Kinetics of folding-unfolding. AB - The kinetics of folding/unfolding of cross-linked Lys7-dinitrophenylene-Lys41 ribonuclease A were studied and compared to those of unmodified ribonuclease A (RNase A) at various concentrations of guanidine hydrochloride. The folding of the denatured cross-linked protein involved one fast-folding species (22 +/- 4%) and two slow-folding species, as observed in unmodified ribonuclease A. Also, a nativelike intermediate, analogous to that reported previously for unmodified ribonuclease A [Cook, K. H., Schmid, F. X., & Baldwin, R. L. (1979) Proc. Natl. Acad. Sci. U.S.A. 76, 6157], has been detected on the folding pathway of cross linked ribonuclease A. The extrinsic cross-link between Lys7 and Lys41 did not affect the rate constants for the folding kinetics of these three species. The cross-link did, however, significantly affect the rate constant for unfolding of the native protein. The conformation of the protein in the transition state of the unfolding pathway was deduced from an analysis of the kinetic data. It appears that the 41 N-terminal residues are unfolded in the transition state of the unfolding pathway. Thus, the unfolding pathway of RNase A is sequential in that further unfolding (after the transition state) follows the unfolding of the 41 N-terminal residues. Also, the conformation of the 41 N-terminal residues does not play a role in the folding pathway. Presumably, if the cross-link were introduced instead between two other residues that are in the segment(s) involved in the rate-limiting step(s), it could increase the refolding rate constants and possibly the concentration of fast-folding species. PMID- 4027221 TI - Contact site of histones 2A and 2B in chromatin and in solution. AB - Irradiation of isolated nuclei or of a complex of histones 2A (H2A) and 2B (H2B) with ultraviolet light produces a covalent cross-link between H2A and H2B. Sequence analysis of the peptides isolated from the H2A-H2B dimer formed in solution and in nuclei demonstrated that both dimers are produced through the covalent linkage of Tyr-40 of H2B and Pro-26 of H2A. Tyrosyl residues proximal to Tyr-40 did not produce a cross-link with H2A, thereby indicating that strict conformational parameters are required for production of the H2A-H2B cross-link. We conclude that the precise juxtaposition of Tyr-40 of H2B and Pro-26 of H2A in this region of the H2A/H2B contact site is not altered upon interaction of these histones with H3 and H4 (tetramer), DNA, or other chromosomal components during nucleosome assembly. PMID- 4027222 TI - Accessibility of tyrosyl residues altered by formation of the histone 2A/2B complex. AB - The availability of tyrosyl residues to surface iodination was analyzed for histone 2A (H2A), histone 2B (H2B), and the H2A/H2B complex. When H2A is free in solution (200 mM NaCl, pH 7.4) tyrosine-39 and one or both tyrosines-50 and -57 were readily iodinated. Tyrosines-83 and -121 of H2B were iodinated, both when the histone was free in solution and when it was associated with H2A, while tyrosines-37, -40, and -42 of H2B were not iodinated under either condition. When H2A and H2B were associated or covalently cross-linked, all tyrosyl residues of H2A were unavailable for iodination. We also found that the iodination of nondenatured H2A and H2B did not inhibit formation of the H2A/H2B complex. These results indicate that the amino-terminal regions of the hydrophobic portions of H2A and H2B undergo significant conformational changes upon formation of the H2A/H2B complex. These conformational shifts occur in the same region of the H2A/H2B complex that contains a contact site between H2A and H2B in the nucleosome, thus indicating an involvement of this region in chromatin assembly. PMID- 4027223 TI - 500-MHz 1H NMR studies of ragweed allergen Ra5. AB - The solution conformation of short ragweed allergen Ra5, a protein of 45 amino acid residues cross-linked with four disulfide bridges, has been investigated by 1H NMR spectroscopy at 500 MHz. The aromatic region, which contains resonances from three tyrosines and two tryptophans, has been partially assigned. Two tyrosines titrate with a pK of 10.2; a third tyrosine is buried under the tryptophan resonances, and its pK could not be determined. The two tryptophans reside in different microenvironments; the resonances of one are very similar to those found in random coil structures while the other has dramatically shifted peaks. Nuclear Overhauser effect (NOE) difference spectroscopy is used to define two distinct spin-diffusion systems for the aromatic residues and to further identify several methyl-containing amino acids involved in these systems. Assignments in the methyl region are based on selective decoupling, chemical shifts, NOE difference spectra, and 2-D J-resolved and 2-D J-correlated spectroscopy (COSY) methodology. A unique ring-current-shifted methyl doublet in the Ra5 spectrum titrates into the bulk methyl region with a pK of 10.2. Examination of the COSY map suggests that this resonance belongs to either leucine-1 or isoleucine-38. Chemical removal of the N-terminal leucine did not affect the ring-current-shifted methyl. Therefore, this unique resonance has been assigned to the methyl of isoleucine-38.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4027224 TI - Ninth component of complement: self-aggregation and interaction with lipids. AB - We have investigated environmental conditions that might be of importance for the polymerization of the ninth component (C9) of human complement. In disagreement with earlier reports summarized by Tschopp et al. [Tschopp, J., Muller-Eberhard, H. J., & Podack, E. R. (1982) Nature (London) 298, 534-538] we find no evidence for significant aggregation or loss of hemolytic activity of C9 when incubated at 37 degrees C even after 12 days of incubation. Higher temperatures cause denaturation of the protein and formation of stringlike aggregates. In contrast, short-term proteolysis with 1% (w/w) trypsin at room temperature causes rapid polymerization of part of the C9 into tubular structures (poly-C9), and the remainder of the monomeric C9 is digested. This polymerization reaction is inhibitable by trypsin inhibitor; alpha-thrombin and proteinase K are ineffective in creating polymers. A second discrepancy to the earlier reports is our finding that monomeric C9 immediately interacts with small unilamellar lipid vesicles (SUV) without a required heating step. As a result of this interaction about half of the C9 aggregates to form strings and tubules, and these aggregates cause agglutination of vesicles. The other half of the C9 associates with a second population of SUV without causing a change in Stokes' radius of these vesicles, and no proteinaceous structures are detectable on the vesicle surface by electron microscopy. When these two vesicle populations are tested for their membrane integrity, no release of an encapsulated fluorescent marker can be detected, nor is there leakage of potassium ions across the bilayer membrane since a membrane diffusion potential can be developed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4027225 TI - 1-Palmitoyl-2-pyrenedecanoyl glycerophospholipids as membrane probes: evidence for regular distribution in liquid-crystalline phosphatidylcholine bilayers. AB - We have synthesized 1-palmitoyl-2-pyrenedecanoyl-sn-glycero derivatives of 3 phosphatidylcholine, 3-phosphatidylethanolamine, 3-phosphatidylserine, 3 phosphatidylglycerol, 3-phosphatidylinositol, and 3-phosphatidic acid and investigated their behavior in monolayers and in neat and mixed bilayers. Fluorescence spectroscopy of neat pyrene phospholipid dispersions revealed a well defined thermotropic transition at 13.5-19 degrees C depending on the polar head group. An endotherm coinciding with this transition was observed with differential scanning calorimetry, indicating it to be due to the melting of the lipid acyl chains. For pyrenephosphatidylethanolamine, the endotherm was observed at a much higher temperature (70 degrees C). Compression isotherms obtained at an argon/water interface revealed that the pyrene moiety somewhat increases the mean molecular area of a phospholipid molecule but does not prevent the expression of head-group-dependent packing behavior. Partition of the pyrene lipids between coexisting fluid and solid phases was investigated with fluorometry and calorimetry. Both techniques indicate that these lipids prefer the fluid phase and that this preference is independent of the head group. The rates and apparent activation energies of lateral diffusion in fluid bilayers were found to be similar for most pyrene lipids, suggesting that the lateral movement of phospholipids is not critically dependent on interactions at the head-group level. Lateral distribution of the pyrene lipids in gel and fluid phosphatidylcholine bilayers was studied with the excimer technique and calorimetry. In gel-state dipalmitoylphosphatidylcholine bilayers, the pyrene lipids form clusters. These clusters, however, do not consist of pure pyrene lipid but of aggregates (compounds) of the labeled and unlabeled lipid.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4027226 TI - Enthalpies of ligand binding to bovine neurophysins. AB - Flow microcalorimetry and batch microcalorimetry have been used to survey the energetics of ligand binding by bovine neurophysins I and II. Calorimetry studies were supplemented by van't Hoff analyses of binding constants determined by circular dichroism. Free energies of binding of a series of di- and tripeptides that bind to the strong hormone binding site of neurophysin were partitioned into their enthalpic and entropic components. The results indicate that, at 25 degrees C, the binding of most peptides is an enthalpy-driven reaction associated with negative entropy and heat capacity changes. Studies elsewhere, supported by evidence here, indicate that the principal component of the negative enthalpy change does not arise from the increase in neurophysin dimerization associated with peptide binding. Accordingly, the negative enthalpy change is attributed to direct bonding interactions with peptide and possibly also to peptide-induced changes in tertiary or quaternary organization. Comparison of the binding enthalpies of different peptides indicated two types of bonding interactions that contribute to the negative enthalpy change of peptide ligation. Substitution of an aromatic- or sulfur-containing side chain for an aliphatic side chain in position 1 of bound peptides led to increases in negative enthalpy of from 1 to 6 kcal/mol, demonstrating that interactions typically classified as hydrophobic can have a significant exothermic component at 25 degrees C. Similarly, loss of hydrogen bonding potential in the peptide decreased the enthalpy change upon binding, in keeping with the expected enthalpic contribution of hydrogen bonds. In particular, the data suggested that the peptide backbone between residues 2 and 3 and the phenolic hydroxyl group in position 2 participate in hydrogen bonding.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4027227 TI - Formation of microtubules at low temperature by tubulin from antarctic fish. AB - Tubulin was isolated from two species of antarctic fish, Pagothenia borchgrevinki and Dissostichus mawsoni, by cycles of temperature-dependent assembly, centrifugation, disassembly, and centrifugation. The preparations were found to consist almost entirely of tubulin and to contain negligibly small amounts of microtubule-associated proteins. This tubulin polymerized to make microtubules of ordinary dimensions. The formed microtubules appear to be in labile equilibrium with free tubulin dimer at all temperatures observed. In a buffer consisting of 0.1 M 1,4-piperazinediethanesulfonic acid, 2 mM dithioerythritol, 1 mM MgSO4, 2 mM ethylene glycol bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid, and 1 mM guanosine 5'-triphosphate, pH 6.9, the tubulin of P. borchgrevinki has a critical concentration for assembly of 0.046 (+/- 0.008) mg/mL at 35 degrees C and 0.74 (+/- 0.15) mg/mL at the habitat temperature of the fish, -1.8 degrees C. The critical concentration measured at the lower temperature is quite small relative to the critical concentration for formation of mammalian microtubules from pure tubulin at the same temperature, which must be at least 2 orders of magnitude larger. The antarctic fish microtubules may thus be called "cold stable" by comparison with mammalian microtubules. They do not fully dissociate at temperatures near 0 degree C because they are composed of tubulin that assembles more readily at these temperatures than does mammalian tubulin. There is no evidence for the presence of a cold-stabilizing factor in association with the tubulin. These findings suggest that alteration of tubulin may be a means by which some poikilotherms can adapt to a cold environment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4027228 TI - Mechanism of action of thrombin on fibrinogen: NMR evidence for a beta-bend at or near fibrinogen A alpha Gly(P5)-Gly(P4). AB - The following synthetic linear A alpha fibrinogen-like peptides were studied by NMR spectroscopy in aqueous solution: Ac-Asp(P10)-Phe(P9)-Leu-Ala-Glu-Gly(P5) Gly(P4)-Gly(P3)-Val- Arg(P1)-Gly-(P1)-Pro-Arg(P3')-Val-NHCH3 (F-8), Ac-Phe-Leu Ala-Glu-Gly-Gly(P4)-Gly(P3)-Val-Arg-Gly-Pro-NHCH3 (F-6), Ac-Leu-Ala-Glu-Gly Gly(P4)-Gly(P3)-Val-Arg-Gly-Pro-NHCH3 (F-7), and Ac-Gly-Gly(P4)-Gly-(P3)-Val-Arg Gly-Pro-NHCH3 (F-9). The temperature dependence of the amide proton chemical shift is smaller by approximately 22% for the Gly(P3) amide proton in F-9, F-6, and F-8 and is similarly smaller for the Gly(P4) amide proton in F-6 and F-8, but not F-9, relative to the other amide protons in these peptides. The exchange rates with solvent water for the Gly(P3) amide proton in each of these four peptides were determined by solvent spin saturation transfer experiments. The exchange rate constant for the Gly(P3) amide proton of F-8 was half that of the rate constant determined for this proton in F-9, F-7, and F-6. In conjunction with previously reported data for the rate of hydrolysis of the Arg(P1)-Gly(P1') bond by thrombin, these results suggest that there is a beta-bend at Gly(P5) Gly(P4), possibly stabilized by salt links between Asp(P10) and Arg(P3') and between phosphorylated Ser(P14) and Arg(P7'), which brings Phe(P9) close to the hydrolyzable Arg-Gly bonds.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4027229 TI - Exchange of histones H1, H2A, and H2B in vivo. AB - We have asked whether histones synthesized in the absence of DNA synthesis can exchange into nucleosomal structures. DNA synthesis was inhibited by incubating hepatoma tissue culture cells in medium containing 5.0 mM hydroxyurea for 40 min. During the final 20 min, the cells were pulsed with [3H]lysine to radiolabel the histones (all five histones are substantially labeled under these conditions). By two electrophoretic techniques, we demonstrate that histones H1, H2A, and H2B synthesized in the presence of hydroxyurea do not merely associate with the surface of the chromatin but instead exchange with preexisting histones so that for the latter two histones there is incorporation into nucleosome structures. On the other hand, H3 and H4 synthesized during this same time period appear to be only weakly bound, if at all, to chromatin. These two histones have been isolated from postnuclear washes and purified. Some possible implications of in vivo exchange are discussed. PMID- 4027230 TI - A new variant of the anion transport protein in human erythrocytes. AB - The major plasma membrane protein of human erythrocytes is the anion transport protein, termed protein 3. We previously reported a variant form of protein 3 that is elongated on the amino-terminal end of the molecule, which is exposed on the cytoplasmic side of the membrane, but otherwise its features are identical with those of the normal molecule. We have termed this molecule protein 3 variant 1. We now report a new variant form, protein 3 variant 2. The erythrocyte donor was a double heterozygote whose red cells possess a normal protein 3 and a protein 3 variant which is elongated and possesses a second variation at the 4,4' diisothiocyano-2,2'-stilbenedisulfonic acid (DIDS) reactive site. Variant 2 reacts with 4,4'-diisothiocyano-1,2-diphenylethane-2,2'-disulfonic acid (H2DIDS) more readily than does the normal molecule. At high pH values, H2DIDS acts as a bifunctional cross-linking agent; it cross-links the proteolytic products generated by Pronase (or chymotrypsin) treatment of variant 2 less efficiently than noted for normal protein 3 or the first variant. Thus, the newly identified molecule has an alteration at the DIDS reactive site, which is near the outer surface of the membrane. The results can be interpreted as indicating that the DIDS binding site of variant 2 is more exposed than the normal molecule, but further removed from the site on the carboxyl-terminal fragment involved in cross linking. Although there is a difference in the reactivity of the two protein 3 chains in variant 2, the reaction of variants 1 and 2 and normal cells with varying concentrations of [3H]H2DIDS results in the same amount of incorporation in all cells. Since protein 3 exists as a dimer or higher aggregate in the membrane, these results may indicate an interaction between monomers.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4027232 TI - H+- and Ca2+-induced fusion and destabilization of liposomes. AB - A new liposome fusion assay has been developed that monitors the mixing of aqueous contents at neutral and low pH. With this assay we have investigated the ability of H+ to induce membrane destabilization and fusion. The assay involves the fluorophore 1-aminonaphthalene-3,6,8-trisulfonic acid (ANTS) and its quencher N,N'-p-xylylenebis(pyridinium bromide) (DPX). ANTS is encapsulated in one population of liposomes and DPX in another, and fusion results in the quenching of ANTS fluorescence. The results obtained with the ANTS/DPX assay at neutral pH give kinetics for the Ca2+-induced fusion of phosphatidylserine large unilamellar vesicles (PS LUV) that are very similar to those obtained with the Tb3+/dipicolinic acid (DPA) assay [Wilschut, J., & Papahadjopoulos, D. (1979) Nature (London) 281, 690-692]. ANTS fluorescence is relatively insensitive to pH between 7.5 and 4.0. Below pH 4.0 the assay can be used semiquantitatively by correcting for quenching of ANTS due to protonation. For PS LUV it was found that, at pH 2.0, H+ by itself causes mixing of aqueous contents, which makes H+ unique among the monovalent cations. We have shown previously that H+ causes a contact-induced leakage from liposomes composed of phosphatidylethanolamine and the charged cholesteryl ester cholesteryl hemisuccinate (CHEMS) at pH 5.0 or below, where CHEMS becomes protonated. Here we show that H+ causes lipid mixing in this pH range but not mixing of aqueous contents. This result affirms the necessity of using both aqueous space and lipid bilayer assays to comprehend the fusion event between two liposomes. PMID- 4027231 TI - Proton-induced fusion of oleic acid-phosphatidylethanolamine liposomes. AB - Liposomes composed of oleic acid and phosphatidylethanolamine (3:7 mole ratio) aggregate, become destabilized, and fuse below pH 6.5 in 150 mM NaCl. Fusion is monitored by (i) the intermixing of internal aqueous contents of liposomes, utilizing the quenching of aminonaphthalene-3,6,8-trisulfonic acid (ANTS) by N,N' p-xylylenebis(pyridinium bromide) (DPX) encapsulated in two separate populations of vesicles, (ii) a resonance energy transfer assay for the dilution of fluorescent phospholipids from labeled to unlabeled liposomes, (iii) irreversible changes in turbidity, and (iv) quick-freezing freeze-fracture electron microscopy. Destabilization is followed by the fluorescence increase caused by the leakage of coencapsulated ANTS/DPX or of calcein. Ca2+ and Mg2+ also induce fusion of these vesicles at 3 and 4 mM, respectively. The threshold for fusion is at a higher pH in the presence of low (subfusogenic) concentrations of these divalent cations. Vesicles composed of phosphatidylserine/phosphatidylethanolamine or of oleic acid/phosphatidylcholine (3:7 mole ratio) do not aggregate, destabilize, or fuse in the pH range 7-4, indicating that phosphatidylserine and phosphatidylcholine cannot be substituted for oleic acid and phosphatidylethanolamine, respectively, for proton-induced membrane fusion. Freeze-fracture replicas of oleic acid/phosphatidylethanolamine liposomes frozen within 1 s of stimulation with pH 5.3 display larger vesicles and vesicles undergoing fusion, with membrane ridges and areas of bilayer continuity between them. The construction of pH-sensitive liposomes is useful as a model for studying the molecular requirements for proton-induced membrane fusion in biological systems and for the cytoplasmic delivery of macromolecules. PMID- 4027233 TI - Kinetics of pH-dependent fusion between influenza virus and liposomes. AB - The pH-dependent fusion between influenza virus and liposomes (large unilamellar vesicles) has been investigated as a model for the fusion step in the infectious entry of the virus into cells. Fusion was monitored continuously, with a fluorescence assay based on resonance energy transfer (RET) [Struck, D. K., Hoekstra, D., & Pagano, R. E. (1981) Biochemistry 20, 4093-4099], which allows an accurate quantitation of the fusion process. Evidence is presented indicating that the dilution of the RET probes from the liposomal bilayer into the viral membrane is not due to transfer of individual lipid molecules. The initial rate and final extent of the fusion reaction increase dramatically with decreasing pH, fusion being virtually complete within 1 min at pH 4.5-5.0. From experiments in which the ratio of virus to liposomes was varied, it is concluded that virus liposome fusion products continue to fuse with liposomes, but not with virus. Fusion is most efficient with liposomes consisting of negatively charged phospholipids, while phosphatidylcholine and sphingomyelin are inhibitory. The reaction is completely blocked by an antiserum against the virus and inhibited by pretreatment of the virus with trypsin. The effect of proteolytic pretreatment at pH 7.4 is enhanced after preincubation of the virus at pH 5.0, consistent with the occurrence of a low pH induced, irreversible, conformational change in the viral fusion protein, the hemagglutinin (HA), exposing trypsin cleavage sites. When, after initiation of the fusion reaction at pH 5.0, the pH is readjusted to neutral, the process is arrested instantaneously, indicating that the low pH induced conformational change in the HA protein, in itself, is not sufficient to trigger fusion activity. PMID- 4027234 TI - Chronic ethanol increases liver plasma membrane fluidity. AB - Purified plasma membrane fractions of cultured well-differentiated Reuber H35 hepatoma cells were studied after growth in the presence or absence of ethanol. Growth of cells in the presence of ethanol significantly increased plasma membrane 5'-nucleotidase activity but did not influence sodium-potassium adenosinetriphosphatase activity. Fluorescence polarization of lipophilic probes was used to study membrane lipid structure. Steady-state polarization of diphenylhexatriene (DPH), a probe of the hydrophobic core, was significantly lower in plasma membranes from cells grown in 80 mM ethanol for 3 weeks, compared to controls. Decreased polarization of DPH in plasma membranes was observed after 3-weeks growth of cells in as little as 1 mM ethanol. A 1-h exposure to 80 mM ethanol had no effect. Altered DPH polarization was due to a decrease in the order parameter of the probe. The rotational correlation time of the probe was virtually unchanged. Chronic ethanol treatment of cells did not alter the polarization of the membrane surface probe trimethylammoniodiphenylhexatriene. Plasma membranes from cells grown in 80 mM ethanol had decreased contents of both phospholipid and unesterified cholesterol, but the cholesterol to phospholipid ratio was unchanged. The percentages of sphingomyelin and phosphatidylserine in plasma membrane phospholipids were significantly decreased after ethanol treatment, while the phosphatidylcholine/sphingomyelin ratio was increased by 42%. Vesicles prepared from total plasma membrane lipids of ethanol-treated cells, as well as vesicles prepared from polar lipids alone, showed the same alterations in DPH polarization as did plasma membranes. The importance of ethanol metabolism in the observed plasma membrane changes was demonstrated in two ways.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4027235 TI - Transmembrane topology of acetylcholine receptor subunits probed with photoreactive phospholipids. AB - The domains of the acetylcholine receptor subunits that contact the lipid phase were investigated by hydrophobic photolabeling of receptor-rich membrane fragments prepared from Torpedo marmorata and Torpedo californica electric organs. The radioactive arylazido phospholipids used carry a photoreactive group, either at the level of the lipid polar head group (PCI) or at the tip of the aliphatic chain (PCII), and thus probe respectively the "superficial" and "deep" regions of the lipid bilayer. The four subunits of T. marmorata and T. californica acetylcholine receptor reacted with both the PCI and PCII probes and thus are all exposed to the lipid phase. Ligands known to stabilize different conformations of the acetylcholine receptor (nicotinic agonists, snake alpha toxin, and noncompetitive blockers) did not cause any significant change in the labeling pattern. The acetylcholine receptor associated 43 000-dalton v1 protein did not react with any of the probes. A striking difference in labeling between T. marmorata and T. californica acetylcholine receptors occurred at the level of the alpha-subunit when the superficial PCI probe was used. An approximately 5 fold higher labeling of the alpha-subunit as compared to the beta-, gamma-, and delta-subunits was observed by using receptor-rich membranes from T. marmorata but not from T. californica. The same difference persisted after purification of the labeled receptors from the two species and was restricted to an 8000-dalton C terminal tryptic peptide. The only mutation observed in this region of the complete alpha-subunit sequence of the two species is the substitution of cysteine-424 in T. marmorata by serine-424 in T. californica.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4027236 TI - Characterization of the platelet agglutinating activity of thrombospondin. AB - Thrombospondin (TSP) is a glycoprotein secreted from the alpha-granules of platelets upon activation. In the presence of divalent cations, the secreted protein binds to the surface of the activated platelets and is responsible for the endogenous lectin-like activity associated with activated platelets. Platelets fixed with formaldehyde following activation by thrombin are agglutinated by exogenously added TSP. Fixed, nonactivated platelets are not agglutinated. The platelet agglutinating activity of TSP is optimally expressed in the presence of 2 mM each of Mg2+ and Ca2+. Reduction of the disulfide bonds within the TSP molecule inhibits its platelet agglutinating activity. TSP bound to the surface of fixed, activated platelets can be eluted by the addition of disodium ethylenediaminetetraacetate. This approach was exploited to identify the region of the TSP molecule containing the platelet binding site. The binding site resides within a thermolytic fragment of TSP with Mr 140 000 but is not present in the Mr 120 000 fragment derived from the polypeptide of Mr 140 000. Since both the Mr 140 000 and 120 000 fragments contain fibrinogen binding sites, this finding suggests that the binding of TSP to the platelet surface requires interaction with other platelet surface components in addition to fibrinogen. The observation that fibrinogen only partially inhibits the TSP-mediated agglutination of fixed, activated platelets is consistent with this interpretation. PMID- 4027237 TI - Solvent isotope effects for lipoprotein lipase catalyzed hydrolysis of water soluble p-nitrophenyl esters. AB - Solvent deuterium isotope effects on the rates of lipoprotein lipase (LpL) catalyzed hydrolysis of the water-soluble esters p-nitrophenyl acetate (PNPA) and p-nitrophenyl butyrate (PNPB) have been measured and fall in the range 1.5-2.2. The isotope effects are independent of substrate concentration, LpL stability, and reaction temperature and hence are effects on chemical catalysis and not due to a medium effect of D2O on LpL stability and/or conformation. pL (L = H or D) vs. rate profiles for the Vmax/Km of LpL-catalyzed hydrolysis of PNPB increase sigmoidally with increasing pL. Least-squares analysis of the profiles gives pKaH2O = 7.10 +/- 0.01, pKaD2O = 7.795 +/- 0.007, and a solvent isotope effect on limiting velocity at high pL of 1.97 +/- 0.03. Because the pL-rate profiles are for the Vmax/Km of hydrolysis of a water-soluble substrate, the measured pKa's are intrinsic acid-base ionization constants for a catalytically involved LpL active-site amino acid side chain. Benzeneboronic acid, a potent inhibitor of LpL catalyzed hydrolysis of triacylglycerols [Vainio, P., Virtanen, J. A., & Kinnunen, P. K. J. (1982) Biochim. Biophys. Acta 711, 386-390], inhibits LpL catalyzed hydrolysis of PNPB, with Ki = 6.9 microM at pH 7.36, 25 degrees C. This result and the solvent isotope effects for LpL-catalyzed hydrolysis of water soluble esters are interpreted in terms of a proton transfer mechanism that is similar in many respects to that of the serine proteases. PMID- 4027238 TI - Alternate substrates and inhibitors of bacterial 4-hydroxyphenylpyruvate dioxygenase. AB - A variety of analogues of (4-hydroxyphenyl)pyruvic acid were synthesized, and the reactions of these compounds with the 4-hydroxyphenylpyruvate dioxygenase from Pseudomonas sp. P.J. 874 were examined. Several of the ring-substituted substrate analogues are reversible inhibitors of the enzyme, the most potent being the competitive inhibitor (2,6-difluoro-4-hydroxyphenyl) pyruvate (Ki = 1.3 microM). Two substrate analogues (2-fluoro-4-hydroxyphenyl)pyruvate and [(4 hydroxyphenyl)thio]pyruvate proved to be alternate substrates for the enzyme. The former compound is converted to (3-fluoro-2,5-dihydroxyphenyl)acetate in an essentially normal catalytic sequence including oxidative decarboxylation, ring hydroxylation, and side-chain migration. The latter compound, however, undergoes oxidative decarboxylation and sulfoxidation to give [(4 hydroxyphenyl)sulfinyl]acetate; ring oxidation is not observed. The implications of these results with regard to the catalytic mechanism of 4 hydroxyphenylpyruvate dioxygenase are discussed. PMID- 4027239 TI - Properties and catalytic function of the two nonequivalent flavins in sarcosine oxidase. AB - Sarcosine oxidase from Corynebacterium sp. U-96 contains 1 mol of noncovalently bound flavin and 1 mol of covalently bound flavin per mole of enzyme. Anaerobic titrations of the enzyme with either sarcosine or dithionite show that both flavins are reducible and that two electrons per flavin are required for complete reduction. Absorption increases in the 510-650-nm region, attributed to the formation of a blue neutral flavin radical, are observed during titration of the enzyme with dithionite or substrate, during photochemical reduction of the enzyme, and during reoxidation of substrate-reduced enzyme. Fifty percent of the enzyme flavin forms a reversible, covalent complex with sulfite (Kd = 1.1 X 10( 4) M), accompanied by a complete loss of catalytic activity. Sulfite does not prevent reduction of the sulfite-unreactive flavin by sarcosine but does interfere with the reoxidation of reduced enzyme by oxygen. The stability of the sulfite complex is unaffected by excess acetate (an inhibitor competitive with sarcosine) or by removal of the noncovalent flavin to form a semiapoprotein preparation where 75% of the flavin reacts with sulfite (Kd = 9.4 X 10(-5) M) while only 3% remains reducible with sarcosine. The results indicate that oxygen and sulfite react with the covalently bound flavin and suggest that sarcosine is oxidized by the noncovalently bound flavin. PMID- 4027240 TI - Side-chain dynamics of two aromatic amino acids in pancreatic phospholipase A2 as studied by deuterium nuclear magnetic resonance. AB - The flexibility of individual amino acid side chains of pancreatic phospholipase A2 in aqueous and micellar solutions was studied with deuterium nuclear magnetic resonance (2H NMR). Bovine pancreatic phospholipase A2 was selectively deuterated at the aromatic ring systems of Trp-3 and Phe-5 and porcine pancreatic phospholipase A2 at Trp-3 only. Solid-state 2H NMR spectra of the lyophilized enzymes exhibited quadrupole splittings on the order of 130 kHz, indicating almost complete immobilization of the aromatic ring systems. Exposure to a water saturated atmosphere did not remove these steric constraints. However, side-chain mobility could be induced for the tryptophyl residue of the bovine enzyme by dissolving this enzyme in aqueous buffer or micellar solution whereas the phenyl ring always remained immobile and served as a probe for the protein's overall rotation. Typical correlation times for the tryptophyl and phenyl aromatic ring systems in aqueous solution were 7 ps and 13 ns (at 20 degrees C), respectively. The correlation time of the phenyl ring was longer than expected for the monomeric protein (approximately 6 ns), suggesting some aggregation of the protein at the high concentrations used for the NMR measurements. Addition of a micellar solution of oleoylphosphocholine had no influence on the motional freedom of the tryptophyl residue but approximately doubled the correlation time of the phenyl ring, indicating an increase of the effective volume of the tumbling particle due to lipid-protein interaction. A different behavior was observed for the Trp-3 residue of porcine phospholipase A2.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4027241 TI - Sedimentation equilibrium measurements of the intermediate-size tobacco mosaic virus protein polymers. AB - Short-column sedimentation equilibrium methods have been applied for the first time to tobacco mosaic virus (TMV) protein (0.1 M ionic strength orthophosphate) at pH 6.5 and at pH 7.0 to estimate molecular weights. Previous sedimentation velocity experiments at pH 6.5, 20 degrees C have led to the conclusion that the major boundary with an S0(20),w value of 24.4 +/- 0.1 S consists of a distribution of polymers which are mainly three-turn, 48-51-subunit helical rod aggregates. The directly measured z-average molecular weights together with sedimentation velocity data are entirely consistent with this assignment of a three-turn aggregate. Molecular weights have also been determined under two conditions where a large mass fraction of the protein sediments with an S0(20),w value of 20.3 +/- 0.2 S. At pH 6.5, 6-8 degrees C, the aggregates in this boundary are metastable and correspond to 50-60% of the preparation. At pH 7.0, 20 degrees C at equilibrium, 65-75% of the protein sediments at 20.3 S. The 20.3S boundary is very similar under both conditions and is interpreted as being composed of a distribution of protein aggregates centered about 39 +/- 2 subunits. This result is important in the interpretation of previous kinetic measurements of TMV self-assembly. The current view is that the 34-subunit structure of TMV protein, in the form of a cylindrical disk which is made up of two 17-subunit layers and has been characterized in single-crystal X-ray diffraction studies, plays a central role in the initial binding steps with RNA. The present results are not consistent with the view that there is a significant concentration of the TMV protein disk structure in solution under the usual conditions of TMV self-assembly. PMID- 4027242 TI - Tobacco mosaic virus protein aggregates in solution: structural comparison of 20S aggregates with those near conditions for disk crystallization. AB - Previous X-ray studies (2.8-A resolution) on the crystals of tobacco mosaic virus protein (TMVP) grown from solutions containing high salt have characterized the structure of the protein aggregate as a bilayered cylindrical disk formed by 34 identical subunits [Bloomer, A.C., Champness, J.N., Bricogne, G., Staden, R., & Klug, A. (1978) Nature (London) 276, 362-368]. Under low-salt conditions, 20S aggregates are in equilibrium with 4S species and involved in the efficient nucleation of TMV assembly in vitro [Butler, P.J.G. (1984) J. Gen. Virol. 65, 253 279]. We have investigated by sedimentation velocity and near-UV circular dichroism (CD) measurements the structure of 20S aggregates in low salt (I = 0.1 potassium phosphate at pH 7.0 and 20 degrees C) and the aggregates in high salt [0.2 M (NH4)2SO4 in I = 0.1 tris(hydroxymethyl)aminomethane hydrochloride at pH 8.0 and 20 degrees C, close to the conditions under which TMVP crystallizes as disk aggregates]. At high salt, we observe structures (presumably stacks of disks) having s20,w values around 40, 45, and 50 S, but not the 20S species present in low-salt buffers. The near-UV CD spectrum of 20S aggregates has been obtained for the first time, using computer techniques, from the spectra of the 4S-20S equilibrium mixture and the 4S species. This spectrum of 20S aggregates differs dramatically from that of the stacks of disks examined at both high and low salt (into which the stacks can be returned by dialysis), indicating that the difference is not a solvent effect.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4027243 TI - Effect of various anions on the stability of the coiled coil of skeletal muscle myosin. AB - The stability of skeletal myosin rod was studied by following the dependence of both papain digestion kinetics and helix-coil transition temperatures on the concentration of neutral salts. The rate of papain-catalyzed digestion of rod to form subfragment 2 and light meromyosin was strongly dependent on chloride concentration but essentially independent of acetate concentration up to 2.0 M. The rod exhibited a biphasic melting curve in 0.6 M NaCl, 5 mM phosphate, and 0.1 mM ethylenediaminetetraacetic acid (EDTA), pH 7.3, with transitions at 45 and 53 degrees C. In 0.6 M CH3COONa, 5 mM phosphate, and 0.1 mM EDTA, pH 7.3, the transitions occurred at 50 and 58 degrees C, respectively. Transition temperatures were obtained with a novel curve-fitting method. The effect of increasing chloride ion concentration on melting profiles was 2-fold. Below 0.6 M salt, the two transition temperatures, Tm,1 and Tm,2, depended on salt concentration such that increasing NaCl concentration caused a small stabilization of the helix while increasing acetate concentration caused the helix to become markedly more stable. Between 0.6 and 1.0 M, variation of chloride concentration had almost no effect on the thermal stability of the rod while increasing acetate concentration increased its stability considerably. Above 1.0 M NaCl, the melting profiles became broad with a third transition being observed (e.g., at 3.0 M, Tm,3 = 38 degrees C), indicating the existence of a region which has a tendency to be destabilized by chloride. The third transition was not observed at comparable concentrations of acetate. This effect of chloride was not expected on the basis of its position in the Hofmeister series.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4027244 TI - Fluorescence of delta 5,7,9(11),22-ergostatetraen-3 beta-ol in micelles, sterol carrier protein complexes, and plasma membranes. AB - The fluorescent sterol analogue delta 5,7,9(11),22-ergostatetraen-3 beta-ol (dehydroergosterol) was synthesized and purified by reverse-phase high performance liquid chromatography. Dehydroergosterol in aqueous solution had a critical micelle concentration of 25 nM and a maximum solubility of 1.3 microM as ascertained from fluorescence polarization and light scattering properties, respectively. Several lines of evidence indicated a close molecular interaction of dehydroergosterol with purified rat liver squalene and sterol carrier protein (SCP). SCP increased the maximal solubility of dehydroergosterol in aqueous buffer. The fluorescence emission spectrum of dehydroergosterol was blue shifted upon addition of SCP. The fluorescence lifetime of dehydroergosterol in aqueous buffer was 2.3 ns; addition of SCP resulted in the appearance of a second lifetime component near 12.4 ns. The SCP increased the fluorescence polarization of monomeric dehydroergosterol in aqueous buffer from 0.033 to 0.086. Scatchard analysis of the binding data indicated that dehydroergosterol interacted with purified rat liver SCP with an apparent KD = 0.88 microM and Bmax = 4.8 microM. At maximal binding, 1.0 mol of dehydroergosterol was specifically bound per mole of SCP. The close molecular interaction of dehydroergosterol with SCP was also demonstrated by energy-transfer experiments. The intermolecular distance between SCP and bound dehydroergosterol was evaluated by fluorescence energy transfer from tyrosine residues of SCP to the conjugated triene series of double bonds in dehydroergosterol. The transfer efficiency was 36%, and R, the apparent distance between the tyrosine energy donor and the dehydroergosterol energy acceptor, was 19 A. The significance of these data obtained in vitro for dehydroergosterol interaction with SCP was also tested in vivo.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4027245 TI - Composition and physical properties of lipids from plasma membranes of dog kidney. AB - Lipid composition, physical state of major phospholipid classes and transbilayer migration of phosphatidylcholine have been determined in plasma membranes of the dog kidney. The lipid composition of brush-border membranes markedly differs from that of antiluminal membranes with respect to: (a) the total phospholipid content; (b) the cholesterol to phospholipid ratio (C/P); (c) the distribution of the major phospholipid classes. Sphingomyelin present in large amounts in both luminal and antiluminal membranes extracts exhibits a transition of phase between 20 and 44 degrees C approximately. In the range of temperature studied (5-55 degrees C) no phase transitions were detected for the other phospholipid species. Our data suggest that: (1) at physiological temperature the higher C/P ratio of brush-border membranes is in large part responsible for their lower fluidity; (2) both the relatively low cholesterol and high sphingomyelin contents contribute to the thermotropic transitions observed in intact membranes. Finally transbilayer migration of phosphatidylcholine in brush-border membranes is a very slow process with a half time of 6.5 h at 37 degrees C which compares with that of other biological membranes. PMID- 4027246 TI - Carrier-mediated choline uptake by Krebs II ascites cells. AB - Krebs II ascites cells have a low affinity uptake system for choline (Km = 36 microM, Vm = 76 nmol/min per 2 X 10(8). Choline entered the cells and was rapidly phosphorylated (95% of total intracellular soluble label). Trans acceleration of labeled choline from cells preloaded with radiolabeled choline and postincubated in the presence of unlabeled choline indicates that choline transport in Krebs II ascites cell is carrier mediated. Ethanolamine competed for the choline carrier. The uptake was reduced by hemicholinium-3, iodoacetamide and ouabain. The mechanism of choline transport in Krebs II ascites cells is in agreement with a linear transport model. PMID- 4027247 TI - Gangliosides reduce leakage of aqueous-space markers from liposomes in the presence of human plasma. AB - We have studied the role of glycolipids in reducing leakage of aqueous-space markers from liposomes, composed primarily of egg phosphatidylcholine, in the presence of human plasma. Liposomes were either small unilamellar (SUV) or large unilamellar (LUV). Leakage of liposome contents as affected by the incorporation into the liposomal bilayer of mono-, di-, or trisialogangliosides (GM, GD, GT) at different molar ratios in the presence or absence of cholesterol was examined. Leakage from liposomes decreased with increasing ganglioside sialic acid. Asialogangliosides had no effect on calcein leakage in the presence of plasma. The stabilizing effect of gangliosides and cholesterol was synergistic, and SUV containing 10 mol% GT and 33 mol% cholesterol had a half-life for leakage of calcein in plasma at 37 degrees C approaching 24 hours. LUV in the presence of plasma retained their contents longer than SUV, and gangliosides had an additional stabilizing effect. Phosphatidylserine and sulfatides were also capable of substituting for gangliosides in stabilizing liposomes to plasma induced leakage. It appears that gangliosides stabilize liposomes in plasma at least in part through their ability to impart surface negative charge. PMID- 4027248 TI - Effects of N-ethylmaleimide on ouabain-insensitive cation fluxes in human red cell ghosts. AB - In red cells of several species, the sulfhydryl reagent N-ethylmaleimide activates a Cl- -dependent, ouabain-resistant K+ transport pathway. Here we report our attempts to demonstrate ouabain-resistant Cl- -dependent K+ fluxes stimulated by N-ethylmaleimide in resealed human red cell ghosts using Rb+ as a K+ analogue. In contrast to intact cells, the rate constants of the base level Rb+ efflux in ghosts were similar in NaNO3 and NaCl (okRb = 0.535 +/- 0.079 h-1 and 0.534 +/- 0.085 h-1, respectively), while 1 mM N-ethylmaleimide stimulated Rb+ efflux strongly in NaNO3 (okRb = 14.26 +/- 1.32 h-1) and moderately in NaCl (okRb = 2.73 +/- 0.54 h-1). This effect was dependent on the presence of internal ATP. Stimulation of Rb+ efflux was observed in the presence of greater than or equal to 0.2 mM N-ethylmaleimide and increased at pH values approaching 8.0, consistent with titration of SH groups. N-Ethylmaleimide-stimulated Rb+ efflux was approx. 50% inhibited by 100 microM quinine sulfate whereas 1 microM bumetanide had no effect. In NaCl the N-ethylmaleimide-stimulated efflux saturated with initial internal ghost Rb+ concentration, but rates increased linearly in NaNO3. Replacement of external Na+ with glucamine or choline decreased the N-ethylmaleimide-stimulated Rb+ efflux, suggesting a role for external Na+. N-Ethylmaleimide-stimulated Rb+ efflux was greater in buffers with lipophilic anions such as SCN- or NO3- than in solutions with Cl- or acetate. However, the cation selectivity of the pathway studied was low, as Li+ efflux was also stimulated by N-ethylmaleimide. We conclude that the effect of N ethylmaleimide on ouabain-resistant cation effluxes of human red cell ghosts is very different from the selective action of N-ethylmaleimide on Rb+ influxes in intact red cells. PMID- 4027249 TI - Specificity of intestinal brush-border proline transport: cyanine dye studies. AB - The ability of rabbit jejunal brush borders to transport inhibitors of the imino carrier was investigated in membrane vesicles by measuring their ability to depolarize the membrane potential. Membrane potentials were monitored using a voltage-sensitive cyanine dye. Piperidine and pyrrolidine carboxylic acids, which are potent inhibitors of Na+-dependent proline transport (Ki less than 0.5 mM) depolarize the potential in a Na+-dependent, saturable manner indicating transport. On the other hand, N-methylated amino acids, which are fair inhibitors (Ki 2-10 mM), do not depolarize the membrane to any significant extent, but they competitively inhibit the L-proline transport signal. This indicates that these analogs are nontransported inhibitors of the imino carrier. The poor inhibitors niacin and pipolinic acid (Ki greater than 60 mM) depolarize the membrane about twice as much as proline and with low Kf values. This suggests separate carriers for these substrates. PMID- 4027250 TI - Heme-apoprotein interaction in the modified oxyhemoglobin-bis(N maleimidomethyl)ether and in oxyhemoglobin at high Cl-concentration detected by resonance Raman scattering. AB - The dispersion of the depolarization ratio of oxidation and spin-marker lines of oxyhemoglobin-bis(N-maleimidomethyl)ether and oxyhemoglobin at high Cl- concentration (1 M) have been examined for different pH values in the neutral and alkaline regions. The oxidation marker line at 1375 cm-1 shows no pH-dependence in the physiological region for oxyHb-bis(N-maleimidomethyl)ether and a comparatively small variation for oxyHb at a Cl- concentration higher than 0.4 M. The spin-marker line at 1638 cm-1 exhibits a strong pH-dependence of depolarization ratio for high Cl- concentration, but a minor pH-induced variation for oxyHb-bis(N-maleimidomethyl)ether. Interpretation of these data yield the following conclusions: (1) The oxidation marker line monitors symmetry-lowering distortions of the heme group introduced by central coupling to the protein via the Fe-N bond, whereas the spin-marker line monitors peripheral coupling due to heme-protein interaction in the heme pocket. (2) At low Cl- concentrations (below 0.3 M) both types of coupling are present. These are induced by the salt bridge between His 146 beta and Asp94 beta and flexibility of the FG corner. (3) At high Cl- concentrations the salt bridge is missing, eliminating central coupling. (4) In oxyhemoglobin-bis(N-maleimidomethyl)ether, due to constraint of the bis(N maleimidomethyl)ether bridging the FG corner and eliminating its flexibility and the missing salt bridge, both central and peripheral coupling are drastically reduced. PMID- 4027251 TI - Characterization of the actin-binding site on the alkali light chain of myosin. AB - 1H-NMR experiments on myosin subfragment-1 (S1) isoenzymes, containing either the A1 or the A2 alkali light chains (S1(A1) or S1(A2)), have previously suggested the 41-residue proline, alanine and lysine-rich N-terminal extension of A1 to constitute a mobile 'domain' in solution. This segment of the molecule is immobilised in the presence of actin (Prince et al. (1981) Eur. J. Biochem. 121, 213-219). We now establish that the A1 light chain interacts with actin directly, and furthermore, that the binding site appears to be restricted to the terminal 41 residues. This observation carries important consequences for both the structure of the actomyosin complex and the role of myosin isoenzymes. Using the proteinase, thrombin, a technique has been developed in which the A1 light chain is cleaved, releasing the N-terminal 'tail' from an A2-like fragment. The method is shown to be widely applicable to light chains from a variety of sources. The isolated N-terminal fragments from rabbit skeletal and bovine cardiac muscle have been shown to interact directly with actin by a combination of affinity chromatography and 1H-NMR experiments. The 1H-NMR results are similar to those obtained earlier with S1 (ibid) and suggest the terminal alpha-N-trimethylalanine residue (Henry et al. (1982) FEBS Lett. 144, 11-15) to participate in the interaction. PMID- 4027252 TI - Effects of cation binding on the thermal transitions in calmodulin. AB - The thermal transitions in different forms of bovine brain calmodulin (0, 1, 2, 3 and 4 bound Ca2+ ions per molecule) have been studied by means of microcalorimetry, intrinsic tyrosine fluorescence, circular dichroism and infrared spectroscopy. The heating of the apoprotein from 5 to 110 degrees C induces at least three unfolding transitions. The heating of Ca2+-loaded calmodulin causes at least two structural transitions, one of which occurs at relatively low temperatures, from approx. 30 to approx 50 degrees C. The binding of the biologically significant Ca2+, Mg2+, Na+ and K+ ions has been measured at 12, 20, 28, 37 and 50 degrees C by means of the fluorescence method. The values of the binding parameters for these cations do not depend on temperature within the range 12 to 50 degrees C. It has been proposed that the temperature independence of the metal-ion-binding properties of calmodulin is achieved due to the temperature-induced structural changes, which adjust the protein conformation in such a way that the protein-binding parameters remain constant. PMID- 4027253 TI - Reactivities of thiols in myosin rod: effect of magnesium and ionic strength. AB - There are six cysteines in each chain of myosin rod of rabbit skeletal muscle: three are in the S-2 portion, at residues 66, 108 and 410 (Lu, R.C. and Lehrer, S. (1984) Biochemistry 23, 5975-5981). The other three are in the light meromyosin portion, assigned at residues 572, 600 and 770 on the basis of homology between the amino acid sequence in the vicinity of these thiols and that of the rod of nematode myosin (McLachlan, A.D. and Karn, J. (1982) Nature 299, 226-231). Since the thiols are distributed in different regions of the rod, measuring their reactivities under various conditions may provide information on the conformations of these regions. Myosin rod was carboxymethylated with radioactive iodoacetic acid under various conditions. The cysteine-containing peptides were isolated using HPLC from the tryptic digests, and the radioactivity incorporated into each thiol was measured. In the denatured state all six thiols were equally reactive. In the native state, all thiols have low reactivity, the reactivity of Cys-108 or -410 is only 0.1% of that in the denatured state, Cys 600 exhibited the highest reactivity, about 20-times that of Cys-410; Cys-66, 572 and -770 had 2-4-times that of Cys-410. When the rods formed filaments, the reactivities of all cysteines further decreased: Cys-66, -108 and -770 were reduced to 50%, while Cys-410, -572 and -600, located in the middle of the rod, were reduced to 20-30% of their reactivities in the monomeric form. In the presence of Mg2+ the reactivity of Cys-108 increased by 20%, whereas Cys-572 decreased by 50%. The results are consistent with the view that metal ions affect the conformation of the rod. This may play a role in the mechanism of filament formation and the movement of crossbridges. PMID- 4027254 TI - The molecular abnormality of albumin Parklands: 365 Asp----His. AB - An electrophoretically slow albumin variant was isolated from the plasma of a patient with bisalbuminemia. Reverse-phase peptide mapping revealed a single altered peak when tryptic digests of the normal and variant albumin were compared. After rechromatography and amino acid analysis, a sequence/composition of Cys-Cys-Ala-Ala-Ala-His-Pro,His,Glu,Cys,Tyr,Ala,Lys was obtained for the mutant peptide, while a sequence of Cys-Cys-Ala-Ala-Ala-Asp-Pro-His-Glu-Cys Tyr,Ala,Lys was obtained for the normal peptide. This establishes the mutation as 365 Asp----His and the new albumin has been named albumin Parklands. Interestingly, this mutation results in the loss of the single Asp-Pro bond that is normally present between residues 365 and 366. Predictably, this confers on albumin Parklands a greater resistance to partial acid hydrolysis, a feature which, when employed together with SDS-gel electrophoresis, can be used as a diagnostic test for the presence of this variant. PMID- 4027255 TI - Stereospecific reactivation of human brain and erythrocyte acetylcholinesterase inhibited by 1,2,2-trimethylpropyl methylphosphonofluoridate (soman). AB - Human erythrocyte and brain acetylcholinesterase are preferentially inhibited by the P(-)-isomers of C(+/-)P(+/-)-soman. The enzymes inhibited by the P(-)-isomers behave similarly with respect to oxime-induced reactivation and aging. HI-6 is the best reactivator for C(+)P(-)-soman-inhibited acetylcholinesterases. Oxime induced reactivation of the C(-)P(-)-soman-inhibited acetylcholinesterases is much more difficult to achieve. PMID- 4027256 TI - A density gradient study of the lipoprotein and apolipoprotein distribution in the chicken, Gallus domesticus. AB - Plasma lipoproteins from 5-week old male chickens were separated over the density range 1.006-1.172 g/ml into 22 subfractions by isopycnic density gradient ultracentrifugation, in order to establish the distribution of these particles and their constituent apolipoproteins as a function of density. Lipoprotein subfractions were characterized by electrophorectic, chemical and morphological analyses, and their protein moieties were defined according to net charge at alkaline pH, molecular weight and isoelectric point. These analyses have permitted us to reevaluate the density limits of the major chicken lipoprotein classes and to determine their main characteristics, which are as follows: (1) very-low-density lipoproteins (VLDL), isolated at d less than 1.016 g/ml, were present at low concentrations (less than 0.1 mg/ml) in fasted birds; their mean diameter determined by gradient gel electrophoresis and by electron microscopy was 20.5 and 31.4 nm respectively; (2) as the the density increased from VLDL to intermediate density lipoproteins (IDL), d 1.016-l.020 g/ml) and low-density lipoproteins (LDL, d 1.020-1.046 g/ml), the lipoprotein particles contained progressively less triacylglycerol and more protein, and their Stokes diameter decreased to 20.0 nm; (3) apolipoprotein B-100 was the major apolipoprotein in lipoproteins of d less than 1.046 g/ml, with an Mr of 350000; small amounts of apolipoprotein B-100 were detectable in HDL subfractions of d less than 1.076 g/ml; urea-soluble apolipoproteins were present in this density range as minor components of Mr 38000-39000, 27000-28000 (corresponding to apolipoprotein A-1) and Mr 11000-12000; (4) high density lipoprotein (HDL, d 1.052-1.130 g/ml) was isolated as a single band, whose protein content increased progressively with increase in density; the chemical composition of HDL resembled that of human HDL2, with apolipoprotein A-1 (M 27000-28000) as the major protein component, and a protein of Mr 11000-12000 as a minor component; (5) heterogeneity was observed in the particle size and apolipoprotein distribution of HDL subfractions: two lipoprotein bands which additional apolipoproteins of Mr 13000 and 15000 were detected. These studies illustrate the inadequacy in the chicken of the density limits applied to fractionate the lipoprotein spectrum, and particularly the inappropriateness of the 1.063 g/ml density limit as the cutoff for LDL and HDL particle populations in the species. PMID- 4027257 TI - Reciprocal effects of energy utilization on palmitate oxidation and esterification in hepatocytes of fed rats. AB - The effects of the energy-dependent process of urea synthesis from NH4Cl on the partition of [1-14C]palmitate between oxidation and esterification were examined in hepatocytes of fed rats. A high rate of urea formation from NH4Cl resulted in stimulation of total palmitate oxidation by 25 and 15% at 0.2 and 1 mM fatty acid, respectively. The stimulation of palmitate oxidation was reciprocally correlated with diminished palmitate incorporation into lipids, mainly triacylglycerols. This relationship was almost stoichiometric. NH4Cl increased the palmitate oxidation/esterification ratio from 0.72 to 1.13 and from 0.94 to 1.36 in the presence of 0.2 mM and 1 mM palmitate, respectively. The transaminase inhibitor, aminooxyacetate, strongly inhibited urea synthesis from NH4Cl, had little effect on the low beta-hydroxybutyrate/acetoacetate ratio in the presence of NH4Cl, completely reversed the changes in palmitate metabolism caused by NH4Cl and did not affect palmitate metabolism in the absence of NH4Cl. Therefore, the increased utilization of energy for urea synthesis was the causative factor by which NH4Cl stimulated total palmitate oxidation and led in consequence to its decreased esterification into lipids. Accordingly, these observations indicate that in liver cells the rate of ATP utilization is one of the determinants of triacylglycerol synthesis. PMID- 4027258 TI - Sex-specific difference of the galabiosylceramide level in the glycosphingolipids of human thyroid. AB - The glycosphingolipids of human thyroid were isolated and characterized by gas liquid chromatography and sequential enzymic hydrolysis. The major purified components were identified as glucosyl- and galactosyl-ceramides, lactosyl- and galabiosylceramides, globotriaosyl- and globotetraosylceramides. The long-chain base analyses showed a high proportion of phytosphingosine in glycosylceramide and galabiosylceramide. Fatty acids in 22:0, 24:0, 24:1 prevailed, especially in the cerebroside fraction, with a significant content of alpha-hydroxylated species in galactosylceramide. Female thyroid had a very low content of galabiosylceramide and a higher content of glucosylceramide, as compared to male. No significant difference was found in the other neutral glycosphingolipids and gangliosides. PMID- 4027259 TI - The specificity of triacylglycerol synthesis for medium-chain fatty acids in rat and human adipose preparations. AB - The availability of medium-chain fatty acids as substrates for triacylglycerol synthesis was studied in cultured and suspended rat adipocytes and in pieces of human adipose tissue. Octanoate was virtually excluded from glycerol 3-phosphate esterification while serving as a substrate for diacylglycerol esterification. This specificity was similar to that of cultured rat hepatocytes. PMID- 4027260 TI - Secretion of human gastric lipase from dispersed gastric glands. AB - The presence of a triacylglycerol lipase in human gastric juice was described in previous studies. Its source and role in intragastric lipolysis was, however, uncertain. Our study presents definitive evidence for gastric origin of a lipase and its release by secretagogues. Both carbachol and cholecystokinin-8 stimulate release of this enzyme for dispersed human gastric glands. While the two secretagogues had similar efficacies, with nearly a 3-fold stimulation over basal rates, cholecystokinin-8 was about four orders of magnitude more potent in releasing lipolytic activity than carbachol (maximum stimulation at concentrations of 1 X 10(-9) and 1 X 10(-5) M, respectively). Lipolytic activity measured against triolein (18:1), tricaprylin (8:0) and tributyrin (4:0) emulsions was 1.18 +/- 0.12, 4.48 +/- 0.64, and 12.17 +/- 0.88 units (1 unit = 1 mumol free fatty acid released/min per mg protein), respectively. Characterization of the pH optimum for each substrate showed maximum lipolysis at 4.5 for tributyrin, and at 5.5 for tricaprylin and triolein. These results indicate that a lipase which hydrolyzes long-, medium- and short-chain triacylglycerols is secreted by human gastric mucosa. At pH 6.0, the pH of the duodenum, there is appreciable lipolytic activity in the presence of bile salts. This suggests that gastric lipase, in addition to initiating lipolysis in the stomach, might also aid in the digestion of lipids in the duodenum. It remains to be determined whether gastric lipase is distinct from lingual lipase, or is the same enzyme secreted by the lingual serous glands and the gastric mucosa. PMID- 4027261 TI - The phospholipid-N-methyltransferase of rat brain microsomes. AB - The phospholipid-N-methyltransferase activity of rat brain microsomes had an optimum pH of 11.0 in the absence or presence of phosphatidylethanolamine (PE) but pH 10.0 in the presence of phosphatidylmonomethylethanolamine (PMME) or phosphatidyldimethylethanolamine (PDME). An apparent Km for S-adenosyl methonine from 0.10 to 0.12 mM was observed with exogenous methylated phospholipids PMME or PDME. Methylated neutral lipid was the major lipid produced in the absence of the exogenous acceptors. Two exogenous phospholipids, PMME and PDME, significantly stimulated microsomal phospholipid-N-methyltransferase activity and the predicted methylated phospholipids were the major products. PE additions did not cause any stimulation of methylated lipid formation. Preincubation of particles at temperatures from 40 to 100 degrees C resulted in a loss in the microsomal phospholipid-N-methyltransferase activity that was stimulated by PMME and PDME. PMID- 4027262 TI - An endogenous activator protein in human placenta for enzymatic degradation of glucosylceramide. AB - An endogenous, heat-stable and pronase-sensitive activator for enzymatic hydrolysis of glucosylceramide was detected in the crude lysosome-mitochondria fraction of human placenta. Its properties differ distinctly in several important respects from those of the previously described glucosylceramidase activator. The activator reported here had no effect on crude glucosylceramidase with either glucosylceramide or 4-methylumbelliferyl-beta-D-glucopyranoside as the substrate in the presence of either sodium taurocholate or phosphatidylserine. On the contrary, glucosylceramide hydrolysis by the enzyme partially purified through Octyl-Sepharose 4B chromatography was stimulated by this activator 6-9-fold in the presence of either sodium taurocholate or phosphatidylserine. The Km for glucosylceramide in the presence of the activator was 1/3 of that without the activator. In the crude enzyme fraction, the activator was present in a 16-fold excess over the minimum amount necessary for full activation of the enzyme. Hydrolysis of the fluorogenic substrate by the post-Octyl-Sepharose enzyme, however, was not stimulated by the activator. Similarly, hydrolysis of galactosylceramide by galactosylceramidase obtained from the same Octyl-Sepharose chromatography was not stimulated. Our observations are consistent with the idea that glucosylceramidase is saturated by, or perhaps tightly associated with, this activator in the placenta and that they are dissociated by the Octyl-Sepharose chromatography. In fact, the properties of the combined post-Octyl-Sepharose enzyme and activator closely mimic those of the crude enzyme without added activator. PMID- 4027263 TI - Characterisation of rat hepatocyte monolayers for investigation of the metabolism of bile salts. AB - Rat hepatocyte monolayers were maintained for periods up to 24 h during which time their viability was greater than 85%. Using specific radioimmunoassays, the hepatocyte monolayers were shown to synthesise conjugated cholic, chenodeoxycholic and beta-muricholic acids. Feeding the bile salt sequestrant, cholestyramine, to donor animals increased synthesis of the major bile salt conjugates by the cells. Incubation of hepatocyte monolayers with bovine serum albumin decreased total synthesis of the three bile acids measured, but increased the amount of conjugated chenodeoxycholic acid detected. In order to test whether the effect of bovine serum albumin on bile salt synthesis was due to binding of bile salts, hepatocyte monolayers were incubated with antiserum to conjugated chenodeoxycholic acid. This treatment increased conjugated chenodeoxycholic acid production but had no effect on the other bile salt conjugates. It is concluded that the increase in conjugated chenodeoxycholic acid synthesis seen with bovine serum albumin and antiserum to conjugated chenodeoxycholic acid is caused by binding of the bile salt in the medium. PMID- 4027264 TI - In vivo distribution and turnover of trans- and cis-10-octadecenoic acid isomers in human plasma lipids. AB - Triacylglycerols containing deuterium-labeled trans-10- and cis-10-octadecenoic acid (10t-18:1, 10c-18:1) plus the triacylglycerol of deuterated cis-9 octadecenoic acid (9c-18:1) were fed as a mixture to two young, adult male subjects. Analysis by mass spectroscopy of the labeled fats in blood samples collected periodically for 48 h allowed the uptake, distribution and turnover of both 10-octadecenoic acid isomers to be directly compared to 9c-18:1. A feature of this study is that actual weight data for the labeled fats were obtained. These data allowed plasma triacylglycerol turnover rates of 3.47-5.13 mg/min per kg to be estimated. Plasma and chylomicron triacylglycerol data also provided evidence that absorption of the deuterated fats mobilized 10-12 g of a triacylglycerol pool present in the intestinal cells. Other results are summarized as follows: the 10t-, 10c- and 9c-18:1 fatty acids were equally well absorbed, both delta 10-18:1 isomers were oxidized more rapidly than 9c-18:1, conversion of the delta 10-18:1 isomers into their corresponding 16:1 isomers was about 3-times faster than for 9c-18:1, the delta 10-18:1 isomers were preferentially incorporated at the 1-acyl and excluded from the 2-acyl position of phosphatidylcholine, esterification of cholesterol with the delta 10-18:1 fatty acids was 2.5-4.3-times slower than for 9c-18:1 and desaturation and elongation rates for the delta 10-18:1 acids were very low. PMID- 4027265 TI - The ionization behaviour of DL-alpha-tocopherol (vitamin E) in model membranes: micelles and vesicles. AB - The ionization behaviour of DL-alpha-tocopherol (vitamin E) has been investigated in dodecyltrimethylammonium bromide (DTAB), hexadecyltrimethylammonium chloride (CTAC) and dodecyldimethyl propiobetaine (DPB) micelles and didodecyldimethylammonium bromide (DDAB) and dimyristoylphosphatidylcholine (DMPC) vesicles. The pKa values for DL-alpha-tocopherol in the aqueous self assembled solutions of DTAB, CTAC, DPB, DDAB and DMPC were 12.0 +/- 0.1, 11.7 +/- 0.1, 13.1 +/- 0.1, 11.0 +/- 0.2 and greater than 14.5, respectively. It is shown how these pKa results confirm that DL-alpha-tocopherol exists predominantly in the un-ionized form when localized in any type of micelle or vesicle at physiological pH values. PMID- 4027266 TI - Contribution of different enzymes to flavoprotein fluorescence of isolated rat liver mitochondria. AB - The fluorescence signal of flavoproteins of rat liver mitochondria was investigated to determine the respective contributions of the various flavoenzymes. About 50% of the overall signal were found to be NAD-linked and caused by alpha-lipoamide dehydrogenase flavin (Em7.4 = -283 mV). Roughly 25% were due to a flavoprotein reducible in a non-NAD-linked reaction. This fluorescent flavoenzyme (Em7.4 = -52 mV) has been tentatively identified as a flavoprotein of the fatty-acid-oxidizing system, most probably the electron transfer flavoprotein. The remaining 25% of the signal are accounted for by flavoenzymes which are reducible by dithionite only. These flavoenzymes were not involved in the flavoprotein fluorescence alterations accompanying changes in electron flow through the respiratory chain. Contributions of other mitochondrial flavoproteins such as succinate dehydrogenase, NADH dehydrogenase, alpha glycerophosphate dehydrogenase, proline dehydrogenase, and choline oxidase, to the overall flavin fluorescence signal of isolated rat liver mitochondria can be neglected. PMID- 4027267 TI - Spatial aspects of mannosyl phosphoryl retinol formation. AB - Rat liver microsomes catalyze the transfer of mannose from GDPmannose to both retinyl phosphate and dolichyl phosphate to form mannosylphosphorylretinol, mannosylphosphoryldolichol and GDP. The two reactions differ in term of reversibility. In fact, a 200-fold isotopic dilution of GDP[14C]mannose by unlabeled GDPmannose causes mannosylphosphoryldolichol labeling to disappear almost completely, while mannosylphosphorylretinol labeling remains at the same level. The same observation can be made if the mannose donor is removed by centrifugation and replaced by excess GDP; again mannosylphosphorylretinol is stable, but mannosylphosphoryldolichol drops down to one-third of its initial level, as expected for, respectively, a non-reversible and a reversible reaction. Placed in an aqueous medium, mannosylphosphorylretinol releases mannose 1 phosphate (beta configuration) whereas it is quite stable when kept in a membranous environment. These results strongly suggest that mannosylphosphorylretinol as soon as it is formed is segregated in such a way that it is no longer available to the back-reaction; the functional consequence of this segregation would be the possibility for mannosylphosphorylretinol to mannosylate some non-polar regions of certain protein chains. PMID- 4027268 TI - Amidation of, and (R)-1-amino-2-propanol attachment to, the corrin ring during vitamin B-12 biosynthesis by Clostridium tetanomorphum extracts. AB - Two intermediate stages in cobalamin biosynthesis, amidation of carboxylic acid groups in the corrin ring and (R)-1-amino-2-propanol attachment at propionic acid position f, have been studied using cell-free extracts from the obligate anaerobe Clostridium tetanomorphum. The preparation of an incomplete corrinoid, probably cobinic acid-a,c,d,e,g-pentaamide, as an in vitro amidation substrate was accomplished via mild acid hydrolysis of cobinamide. Weak, but reproducible activities for both amidation and (R)-1-amino-2-propanol attachment were found in crude, nucleic acid-free and DE-52 column-purified protein fractions. The amidation reaction was glutamine-dependent in crude fractions, but became ammonium ion-dependent in more purified fractions. Significant problems encountered were (a) the weak and unstable character of both enzyme activities, and (b) the irreversible changes in the visible spectra of the incomplete corrinoids employed as substrates caused by use of thiol-reducing agents in the buffers and assays. PMID- 4027269 TI - [Effect of phosphemide in combination with dexamethasone on DNA structure in sarcoma 45]. AB - It is shown that under the influence of phosphemide in combination with dexamethasone some characteristics of tumour DNA (content of 5 methyl cytosine, temperature, interval and enthalpy of melting) approximate the corresponding characteristics of DNA of healthy animals' liver better than under the influence of phosphemide only. PMID- 4027270 TI - [Block improvement of the genetic text as a factor of acceleration of biological evolution]. AB - It is shown that the time required for selecting most perfect sequences can be decreased by several orders at the expense of block-hierarchic principle of biological objects structure. PMID- 4027271 TI - [A model of cooperative rearrangements of biological membranes without changes in the affinity of receptor binding centers]. AB - A mathematical model is proposed for cooperative rearrangements induced by specific ligand in certain biomembrane domains. They are considered as the N valent receptors undergoing rearrangement when n less than or equal to N ligand binding receptor sites are occupied. The model predicts distinct sigmoidal dependence for change of some structural parameter on ligand concentration when the receptor site-ligand affinity remains constant as binding rises (positive cooperativity is absent). PMID- 4027272 TI - [Equilibrium characteristics of calcium binding on the inner surface of membrane vesicles]. AB - A method is proposed for determining equilibrium parameters of calcium binding on the inner surface of membrane vesicules. Based on the studies of concentration relationship of calcium content in vesicules of myometrium sarcolemma (at the equilibrium state) there were determined the values of maximal capacity of Ca2+ binding (12.79 nmole/mg of protein) and the dissociation constants of Ca2+ binding centre complex (62.3 mkM) on the inner surface of the vesicules, and the value of intravesicular volume as well (25.7 mkl/mg of protein). PMID- 4027273 TI - [Effect of cholesterol on the stability of human erythrocyte membranes to electric breakdown]. AB - Electrical stability of human erythrocyte membranes with different cholesterol content was studied. Breakdown in the cell membranes was generated by application of electric pulses with field strengths of 1.4-3.2 kV/cm. The share of perforated cells was registered by measuring hemolysis level. The red blood cells from patients with psoriasis and normal erythrocytes after incubation in the presence of liposomes were used as a model of cells with cholesterol-rich membranes. It was discovered that an increase of cholesterol content in the membranes moved the field-dependent curves to a higher field range. The obtained effect is attributed to the increase of the breakdown membrane potential. Application of high-pulse electric-field technique for investigating the properties of cell membranes is discussed. PMID- 4027274 TI - [Changes in the intensity of the fluorescence of potential-sensitive fluorescent probes in the active transport of Ca2+ in the fragmented sarcoplasmic reticulum]. AB - The dependence of fluorescence intensity changes of potential-sensitive fluorescent probes 3,3'-dipropyl-2,2'-thyodicarbocianine and 1-anilino-8 naphtalenesulphonae on the ATP concentration during Ca2+ transport in fragmented SR of the rabbit skeletal muscle has been studied. An increase in the accumulation of Ca2+ in the SR vesicles caused by ATP is accompanied by an increase in the fluorescence intensity of the potential-sensitive probes. These fluorescence changes are related neither to ATP or Ca2+ effect but are coupled with cation accumulation inside the vesicles since they are not observed in the presence of either EGTA or triton X-100 or in the absence of Mg2+. The results obtained prove the membrane potential generation in SR in the course of ATP dependent Ca2+ transport. PMID- 4027275 TI - [Ambiguity of the solution of the inverse problem of electroencephalography]. AB - It has been shown for homogeneous conducting medium that if different stationary distributions of current sources form identical potential fields on the plane boundary, the difference between these two distributions is the distribution of current sources with all multiple moments equaling zero. Examples of current source distributions are presented which satisfy this condition. PMID- 4027276 TI - [Unequivocal solution of the one-dimensional inverse problem of electroencephalography for point sources]. AB - A point sources system placed in a homogeneous volume conductor with a plane boundary is proved to be uniquely determined by its surface potential field. For the nonlocal sources the inverse problem solution is nonunique. PMID- 4027277 TI - [Formal model of the generation of alpha-rhythm of human electroencephalograms based on principles of statistical dynamics]. AB - Controlling algorithm of different alpha-rhythm generating models in respect to the real mechanism of specific EEG is described. The algorithm is based on known statistical dynamics regulations and specifically upon Gaussian correlation theory of narrow band noise, its envelope and phase. PMID- 4027278 TI - System analysis and nucleic acid sequence banks. AB - The mass of published nucleic acid sequence data has required the design of several computerized data bases. We show that this activity is related to the methodology of System Analysis and that data bases are a means of modeling biological knowledge. As an example, the ACNUC data base we have created is presented. PMID- 4027279 TI - Theory of degenerate coding and informational parameters of protein coding genes. AB - The theory of degenerate coding is presented in a way enabling further application to molecular biology. There are two kinds of redundancy of a degenerate code. The first is due to the excess in codon length and the second to the code degeneracy. If the code is asymmetrically degenerate, the second kind of redundancy can be profitable for control of error rate. This control can be performed just by selective synonymous codon usage. Utilisation of the genetic code is partially influenced by this theoretical possibility. In particular the degree of error protectivity is well correlated with deviation from equiprobability in synonymous codon usage. The biological significance of this fact is discussed. PMID- 4027280 TI - "Neural" computation of decisions in optimization problems. AB - Highly-interconnected networks of nonlinear analog neurons are shown to be extremely effective in computing. The networks can rapidly provide a collectively computed solution (a digital output) to a problem on the basis of analog input information. The problems to be solved must be formulated in terms of desired optima, often subject to constraints. The general principles involved in constructing networks to solve specific problems are discussed. Results of computer simulations of a network designed to solve a difficult but well-defined optimization problem--the Traveling-Salesman Problem--are presented and used to illustrate the computational power of the networks. Good solutions to this problem are collectively computed within an elapsed time of only a few neural time constants. The effectiveness of the computation involves both the nonlinear analog response of the neurons and the large connectivity among them. Dedicated networks of biological or microelectronic neurons could provide the computational capabilities described for a wide class of problems having combinatorial complexity. The power and speed naturally displayed by such collective networks may contribute to the effectiveness of biological information processing. PMID- 4027281 TI - Control properties of perceptual transient and sustained mechanisms. AB - A second order control formulation describing the temporal responses of sustained and transient preceptual processes is investigated. Parametric configurations for the resulting transfer functions are determined from existing experimental data. These data include experiments on impulse response, flicker frequency, subthreshold summation, and masking. PMID- 4027282 TI - Studies of some new phenomena of motion perception. AB - Contrast modulation of a set of features in a Glass pattern invokes, under certain circumstances, the perception of motion in the absence of any physical displacements. The illusion is spatially limited to within about 10' and is governed by contrast relationships. We find that the detected motion in these situations is due to local computations the results of which can be integrated over retinal areas of more than 1 degree. The possible motion detection mechanisms are discussed within the framework of the Reichardt/Hassenstein and Marr/Ullman type of motion detectors. PMID- 4027283 TI - [Inhibition of various stages of DNA replication in sea urchin embryos]. AB - The embryos of the sea urchin Strongylocentrotus intermedius possess the ability to incorporate into their DNAs 2'-deoxynucleosides together with all their bases, i.e., adenine, guanine, cytosine and thymine. This incorporation is inhibited by 3'-amino-2',3'-dideoxynucleosides with the same bases. 5'-Amino-5' deoxynucleosides and 5'-amino-2',5'-dideoxynucleosides moderately inhibit the incorporation of [3H]2'-deoxynucleosides into the DNAs by competing with the latter, presumably at the phosphorylation stage. The most potent inhibiting effect is exerted by 2'-amino-2'-deoxynucleosides and 2'-asido-2' deoxynucleosides; the mechanism of this inhibition is still obscure, however. PMID- 4027284 TI - [The role of free calmodulin in the regulation of calcium-pump activity in erythrocytes]. AB - The activity of Ca-pump in inside-out oriented vesicles obtained from erythrocyte membranes after their 30 min treatment with EGTA at 20 degrees C (membranes A) and 37 degrees C (membranes B) was investigated. It was shown that in membranes A placed into an incubation medium containing 0.1 mM EGTA (pH 7.4) the overall effect of exogenous calmodulin is due to the increase in the maximal activity of the enzyme, its affinity for Ca2+ being unaffected thereby. In membranes B placed into the same medium (pH 6.75) the activation of the Ca-pump by calmodulin is due to the increased affinity for Ca2+ at a constant maximal activity of the enzyme. The dependencies of the value of the calmodulin-stimulated component of membranes A and the Ca2+-binding capacity of calmodulin measured by the intensity of N phenyl-1-naphthylamine fluorescence on the concentration of free Ca2+ are coincident. In the case of membranes B, the stimulation of Ca-pump by calmodulin occurs at much lower Ca2+ concentrations than the Ca2+ binding-induced conformational shifts in calmodulin. The experimental results suggest that the affinity of the Ca-pump for Ca2+ may affect calmodulin existing in a Ca2+ independent state. The hydrophobic interactions between the Ca-calmodulin complex and the Ca-ATPase molecule are apparently essential for the regulation of the maximal enzyme activity. PMID- 4027285 TI - [Fractionation of fragments of skeletal muscle sarcoplasmic reticulum according to their sensitivity to caffeine]. AB - Sarcoplasmic reticulum fragments were fractionated according to the ability of caffeine to selectively block Ca2+ uptake in the population of caffeine-sensitive membranes. The membrane suspension was loaded with calcium in the presence of oxalate, Mg-ATP and caffeine, after which the Ca2+-loaded caffeine-sensitive fragments were separated by sucrose density gradient centrifugation. In Ca2+ unloaded fragments of the supernatant, the sensitivity to caffeine estimated by its ability to diminish the rate of Ca2+ uptake, Ca/ATP ratio and Ca-oxalate capacity amounted to 91-93%. The terms of protein composition, the caffeine sensitive fragments were identified with terminal cystern membranes, while the caffeine-insensitive ones with the SR canalicular membranes. The sensitivity to caffeine may serve as a reliable criterion for estimating the relative content of terminal cystern fragments in different microsomal preparations. PMID- 4027286 TI - [Purification and various properties of asialoglycoprotein receptors from the mouse liver]. AB - The receptor for asialoglycoproteins was isolated from murine liver and was purified by means of biospecific chromatography on sepharose-Asialo-orosomucoid. The obtained receptor with an absorption maximum at 277 nm binds to the nonreducing terminal galactosyl residues of glycoproteins similar to the receptors from liver of other mammalians. The interaction between this receptor and desialylated glycoproteins requires the presence of calcium. The dependence of specific binding on the concentration of [125I]acialo-orosomucoid used as a ligand gives a saturating curve. The dissociation constant for the receptor ligand complex is 0.4 X 10(-9) M. Similar to asialo-orosomucoid, the receptor binds the p-aminophenyl-beta-D-galactopyranoside derivatives of bovine serum albumin, ovalbumin and acid alpha-glucosidase synthesized by us earlier. Possible use of the asialoglycoprotein receptor as a highly specific carrier transporting the modified acid alpha-glucosidase to hepatocyte lysosomes is discussed. PMID- 4027288 TI - [Radioprotective action of catecholamines on a Chinese hamster fibroblast culture]. AB - The radioprotective ability of adrenaline, noradrenaline and isoproterenol in various concentrations has been studied in experiments on cultured Chinese hamster fibroblasts in vitro. Radioprotective effect of isoproterenol is pronounced at 10(-8)M concentration; adrenaline and especially noradrenaline are effective at higher concentrations. The antagonist of beta-adrenergic receptors propranolol blocks the radioprotective effect of catecholamines on cells. The beta-adrenergic mechanism of catecholamines radioprotective action on the mammals cells is under discussion. PMID- 4027287 TI - [Lipid peroxidation in the myocardium in experimental infarct]. AB - Changes in the content of lipid peroxidation (LP) products and activities of antioxidant enzymes--superoxide dismutase, glutathione peroxidase and catalase in myocardium of rats after experimental infarction as well as after pretreatment with antioxidant ionol, beta-adrenoblocker inderal and verapamil, an inhibitor of slow Ca2+-channels have been studied. In the left ventricles of the control animals decreased levels of LP-products (Schiff bases and lipid hydroperoxides) have been registered as compared with right ventricles, accompanied by increased activity of antioxidant enzymes in the left ventricles. In experimental infarction the level of LP products increases and activity of antioxidant enzymes decreases both in ischemic and nonischemic regions of the heart. In nonischemic zone these changes can be prevented by pretreatment with inderal and ionol but not with verapamil. PMID- 4027289 TI - [Action of actinomycin D on the nucleolar function and ultrastructure of a pig embryo kidney cell culture]. AB - It has been shown that the morphofunctional alterations of nucleoli in KEPV cells induced by actinomycin D at 0,05 microgram/ml proceed in two steps. During the first 3 h of actinomycin D action a level of the RNA synthesis in nucleoli falls to 25% from the initial one. Simultaneously the following morphological alterations take place: condensation of the chromatin, infiltration of nucleoli, displacement to outlining regions, increase of the dimensions and reduction of number of fibrillar centres, gradual disappearance of compact fibrillar zone and appearance looplike granular structures. During the following 3-6 h of antibiotic action the RNA synthesis falls slightly, nucleoli dimensions decrease, fibrillar micronucleoli appear. PMID- 4027290 TI - [A device for discrete information input into the Elektronika DZ-28 microcomputer]. AB - A simple matching device destined for the connection of electrophysiological plant with micro-computer "Electronics DZ-28" has been described. The device permits to carry out straight input of information concerning neurones impulsive activity. PMID- 4027292 TI - [Construction of a typology for distribution of body mass by body segments in men using the main component method]. AB - The method of morphotype construction based on the principle components is described. The morphotype system has been constructed for the main circumferences of a man's body including the size index of diametrical dimensions and the character of trunk-limbs distribution of the body mass. According to the second index it is possible to determine the following variants: the centripetal one with the trunk circumferences predominance over the limbs circumferences and the inverted combination-centrifugal type. The geographical regularity values of the morphological indexes for some ethnoterritorial groups of the USSR has been shown. PMID- 4027291 TI - [Characteristics of a cell line obtained from a human hypernephroma]. AB - A stable tumorigenic cell line has been obtained from the human hypernephrome. The culture grew as monolayers of large polygonal cells with foamy cytoplasm and 1-2 nucleoli. The cells formed monolayer after the third day after planting into flask and then formed multilayered growth. The electron microscopic studies of hypernephrome sections revealed the dark and light cells. The hypernephrome cells have characteristics of tumor cells. On the 200th passage the cells are aneuploid with a model number of 62 chromosomes; an acrocentric chromosome in D group is noted as a marker one. The hypernephrome cells are free of Mycoplasma contamination, able to support the several virus replication. PMID- 4027293 TI - [Effect of bacitracin on the sporulation of Bacillus licheniformis 28 KA]. AB - The bacitracin effect on spore germination in Bacillus licheniformis 28 KA--the producer of this antibiotic on media of various composition has been studied. Different intensity of antibiotic synthesis has been revealed on various media. A high content of presynthesized bacitracin has an inhibitory effect on spore germination in B. licheniformis. PMID- 4027294 TI - [Effect of the antiseptic merthiolate and its derivatives on fungi causing deterioration]. AB - The fungistatic activity of merthiolate and its two polymerous derivatives have been investigated using as test cultures fungi producing deterioration. The fungicides sorbtion dynamics by the fungus micelium have been studied, toxicity and inhibition rate of the catalase from different sources have been evaluated. The polymerous derivatives have been found to maintain high fungistatic activity of merthiolate, but possess less toxicity. The sorbtion of the polymerous derivative by the fungal mycelium takes place more effectively than the merthiolate sorbtion. The probable reasons of the high activity of the merthiolate polymerous derivatives are under discussion. PMID- 4027295 TI - Effect of low-dose dopamine infusion on prolactin and thyrotropin secretion in preterm infants with hyaline membrane disease. AB - The effect of low-dose (2-4 micrograms/kg/min) and long-term (greater than or equal to 46 h) dopamine infusion on serum prolactin and thyrotropin concentrations was investigated in 8 preterm infants with hyaline membrane disease. Dopamine was administered for systemic hypotension and/or for impending renal failure. Serum prolactin decreased from 1,314.5 +/- 422.7 microU/ml to 489.9 +/- 464.1 microU/ml (p less than 0.005), while serum thyrotropin fell from 3.77 +/- 2.27 microU/ml to 1.01 +/- 0.25 microU/ml (p less than 0.025) during dopamine infusion. Our data indicate that exogenous dopamine exerts an inhibitory effect on the secretion of prolactin and thyrotropin even in the sick preterm neonate. The role of prolactin in fetal lung maturation and in regulation of the neonatal tissue water stores is discussed. The results of the present study are also useful in explaining the renal effects of long-term low-dose dopamine infusion in the sick preterm infant. PMID- 4027296 TI - Synthesis of C20 and C22 polyunsaturated fatty acids by the placenta of the sheep. AB - Incubation in vitro of sheep placental homogenates with [1-14C] oleic, linoleic and linolenic acids resulted in extensive amounts of radioactivity becoming associated with C20 and C22 polyunsaturated fatty acid products. The fatty acids of the fetal plasma displayed substantial levels of both C20 and C22 polyunsaturated fatty acids, including the n-9 eicosatrienoic fatty acid associated with essential fatty acid deficiency, but extremely low levels of linoleic and linolenic acids. A role for the placenta in the provision to the fetus of a range of C20 and C22 polyunsaturated fatty acids derived from C18 fatty acid precursors is implicated. PMID- 4027298 TI - Journal referees: gatekeepers of science. PMID- 4027297 TI - Increased maternal-fetal transport of fat in diabetes assessed by polyunsaturated fatty acid content in fetal lipids. AB - The distribution of fatty acids was determined by gas-liquid chromatography in total lipid and triglyceride fraction of extracts of several tissues of streptozotocin-diabetic rats and their fetuses on day 20 of pregnancy. In maternal rats, diabetes did not significantly affect fatty acid distribution apart from small changes in the relative content of linoleate in adipose tissue and liver. In the placenta, the fetal carcass and the fetal liver the triglyceride content increased approximately 2-fold as a result of maternal diabetes, in association with the elevation in triglycerides and free fatty acids in the maternal circulation. A pronounced increase in the relative content of linoleate was recorded in the total lipid and triglyceride extracts of placenta (35 and 59%), fetal carcass (56 and 66%) and fetal liver (100 and 205%). Small increases in arachidonate proportion were also seen in some fetal tissues. The large increase in fetal hepatic linoleate indicates that this tissue is an important uptake target of maternal lipids transported in excess into the fetus. The results confirm the previous observations on increased transplacental fat passage in diabetes by demonstrating that the increment in the essential fatty acid, linoleate, parallels the diabetes-induced triglyceride accumulation in the fetoplacental unit. PMID- 4027299 TI - The dexamethasone suppression test in depressed retarded adults: preliminary findings. AB - This study was undertaken to determine the utility of the Dexamethasone Suppression Test (DST) for diagnosing depression in institutionalized mentally retarded persons. Depressed and nondepressed institutionalized mentally retarded persons were given 1 mg dexamethasone for an overnight DST. Serum cortisol concentrations greater than 4 micrograms/dl at both 8:00 AM and 4:00 PM provided discrimination of depressed from nondepressed groups. Also, using the criteria of serum cortisol concentrations greater than 4 micrograms/dl at 8:00 AM and 4:00 PM, at 4:00 PM and 10:00 PM, or at 8:00 AM, 4:00 PM, and 10:00 PM differentiated these groups. These results suggest that the DST may be useful for detecting melancholia among institutionalized retarded persons. PMID- 4027300 TI - Biological stress responses in high and low trait anxious students. AB - In an investigation of biological indicators of stress in normal humans, undergraduate psychology students were differentiated on trait anxiety and assessed under baseline, preexam (stress), and postexam conditions. Assessment at each condition involved drawing 20 ml of blood, followed by self-reporting for selected questionnaires. Self-reports included state anxiety, general psychological symptomatology, dysfunctional attitudes, academic confidence, sleep patterns, and intake of drugs, including alcohol and caffeine. Blood was analyzed for whole blood serotonin content, plasma MHPG, and platelet imipramine binding. Baseline differences between high and low trait anxious students on biological measures were significant only for whole blood serotonin content. Variation across situational conditions was significant for whole blood serotonin, with an increase under the stressful condition for both anxiety groups. Thus, serotonin is highlighted as an important factor in the human response to stress, whereas expected differences in MHPG were not observed. The serotonergic response to stress was not explained by changes in psychological or physical state variables. Changes in serotonin content were positively correlated with changes in platelet imipramine binding. PMID- 4027302 TI - Opposite effects of chronic imipramine treatment on brain and urine MHPG levels in the rat. AB - Acute imipramine (IMI; 20 mg/kg, ip) in rats decreased the brain concentration of 3-methoxy-4-hydroxyphenethylene glycol (MHPG), a metabolite of norepinephrine (NE), to 85% of control 24 hr after injection. In contrast, chronic IMI (20 mg/kg, ip, daily for 14 days) significantly raised brain MHPG levels to 123% of control, while reducing brain NE levels. Urinary MHPG levels were reduced by both acute and chronic IMI treatments, to 52% and 51%, respectively. These data suggest that the brain turnover of NE is reduced after acute IMI, but is elevated after chronic treatment. Although urinary levels of MHPG changed in parallel with brain levels following an acute administration of IMI, such was not the case after chronic administration. We conclude that caution must be used in extrapolating drug-induced changes in urinary metabolite levels to brain amine function. PMID- 4027303 TI - Anorectic behavior, mood, and metabolic and endocrine adaptation to starvation in anorexia nervosa during inpatient treatment. AB - Twenty-two patients with anorexia nervosa were studied at 2-week intervals during treatment on psychiatric wards. In order to characterize the metabolic situation in starvation, levels of free fatty acids, beta-hydroxybutyric acid, and acetoacetate were measured. The endocrine adaptation to starvation was studied by measuring triiodothyronine, noradrenaline, and cortisol. Anorectic symptoms were assessed by the Anorexia Nervosa Inventory Scale (ANIS) and mood changes on the basis of a "Befindlichkeits" Scale (BF). Only half of the patients showed metabolic and endocrine signs of starvation on admission to the hospital, despite low body weight. This group had significantly more severe anorectic symptoms (ANIS) and gained weight at a lesser rate. Metabolic signs of starvation disappeared during the first 4 weeks of therapy in most of the patients. The endocrine indicators for starvation normalized much more slowly, with noradrenaline having the slowest pace. "Bulimics" and "restricters" could not be distinguished from one another by metabolic or endocrine observations. The "bulimics," however, showed more severe anorectic symptoms (ANIS) and a more depressed mood. PMID- 4027301 TI - Platelet monoamine oxidase activity in patients with panic disorder. AB - Preliminary reports have indicated that platelet monoamine oxidase (MAO) activity is elevated in patients with anxiety disorder. We compared MAO activity in 20 drug-free patients with panic disorder with 20 age- and sex-matched normal controls. MAO activity in patients was significantly higher than in normals. MAO activity was not correlated with age or plasma catecholamine levels. The authors speculate about the possible significance of elevated MAO activity in patients with panic disorder. PMID- 4027304 TI - Orienting reaction in patients with night terrors. AB - A polygraphic study of the somatic (electromyogram), autonomic (finger plethysmogram, galvanic skin reaction, respiration, pulse), and electroencephalographic (acoustic-evoked potential and EEG-blocking reaction) components of the orienting reaction elicited by an auditory stimulus was performed in 36 patients with night terrors and in 72 matched subjects in two control groups. The study showed a significantly more intense orienting reaction in patients with night terrors than in normal subjects (Control Group I). Moreover, the orienting reaction intensity in subjects with night terrors was significantly lower than in patients with symptomatic epilepsy (Control Group II). The orienting reactions of patients with night terrors depended on the patient's age, the history of nocturnal episodes, and their clinical form, as well as on etiology. PMID- 4027305 TI - Decreased triiodothyronines in depression: a preliminary report. PMID- 4027306 TI - Attention deficit disorder, amphetamine, and pregnancy. PMID- 4027307 TI - MHPG, ECT, and depression. PMID- 4027308 TI - Somnambulistic behavior associated with abnormal REM sleep in an elderly woman. PMID- 4027309 TI - Phenelzine-induced hypomania: effect of verapamil. PMID- 4027310 TI - Icon formation in chronic schizophrenics. PMID- 4027311 TI - Weight change and the dexamethasone suppression test. PMID- 4027312 TI - Rapid antidepressant activity of destyr gamma endorphin: correlation with urinary melatonin. PMID- 4027313 TI - The human brain: instrument of progress or disaster? PMID- 4027314 TI - Use and misuse of electroconvulsive treatment. AB - For the continued availability of electroconvulsive therapy (ECT) in clinical practice on equal footing with other treatments, and without judicial interference, the following points are essential: ECT should be used or not used on the basis of scientific evidence and not because of public opinion or antipsychiatric propaganda. There should be no hesitation to use ECT in conditions where its omission would mean prolonged suffering, risk of suicide, or death from other causes (deep melancholic syndromes, acute lethal catatonia, psychogenic confusion). ECT should not be used where the effect is short-lived or must be paid at the price of an organic syndrome (schizophrenia, paranoid states, organic confusions). Efficiency should be optimal (oxygen, superficial narcosis, absence of benzodiazepines, generalized tonic-clonic seizures of at least 30-sec duration, maintenance treatment with antidepressive drugs). Safety should be optimal, not only for life but also for cerebral functioning (anesthesiological management, unilateral nondominant stimulation, pulse wave stimuli, appropriate number of treatments, not too closely spaced). The mechanism of action should be the object of further investigation. Such research will open possibilities for finding drugs that can compete with ECT. PMID- 4027315 TI - What does the dexamethasone suppression test identify? AB - The authors studied the Dexamethasone Suppression Test (DST) in chronic pain patients with and without major depression, using items from a modified version of the Hamilton Depression Scale, the Hamilton Anxiety Scale, and the Montgomery Asberg Depression Rating Scale. The purpose of the study was to identify the factor or factors which discriminated DST suppressors from nonsuppressors. The data suggest that depression and its profile are efficient discriminators of suppressors and nonsuppressors. Anxiety-related items were not as good as discriminators. The items that identified nonsuppression were the items that are often seen in combination in endogenous depression. PMID- 4027317 TI - Deficient motor synchrony in schizophrenic disorders: clinical correlates. AB - A laboratory measure of synchronization was used to assess the differential ability of schizophrenics, affectives, and normal controls to take advantage of stimulus predictability. It was hypothesized that (1) schizophrenics will perform on this task in a way that distinguishes them from other groups, (2) clinically observed motor anomalies will be associated with deficient motor synchrony, and (3) deficient motor synchrony will be associated with more severe clinical ratings of thought disorder. Twenty-one schizophrenic, 8 affective, and 16 normal controls were studied. The results were consistent with the hypotheses; schizophrenic subjects had distinctive performance patterns, especially at 40 bpm, which was associated with both motor and thinking disturbance. The authors discuss additional analyses that suggest that deficient motor synchrony is associated with negative symptoms, certain ward behaviors, and not with demographic variables, and that among unmedicated schizophrenic subjects, the performance patterns are worse. PMID- 4027316 TI - Habituation and cortisol dysregulation in depression. AB - The relationship between hypothalamic-pituitary-adrenal (HPA) dysregulation and skin conductance measures of habituation, stimulus specificity, and dishabituation was investigated in psychiatric patients exhibiting depressed affect. As a group, depressed patients showed a relative failure to dishabituate when compared with control subjects. Nonsuppression of cortisol following dexamethasone was associated with decreased response specificity as reflected in direct response measures and baseline skin conductance level. The impairment of response specificity to a novel stimulus is consistent with previous studies demonstrating a role for cortisol in the regulation of selective attention processes. PMID- 4027318 TI - Repeated significance tests for clinical trials with a fixed number of patients and variable follow-up. AB - Group-sequential tests may be applied to trials in which the number of patients is fixed, a response variable is measured for each patient at successive follow up visits, and the accumulated responses are compared across treatment groups. The standard theory is inapplicable because the increments in the accumulated responses are no longer independent. An adjustment can be made to allow for the ratio of between-patient to within-patient variance and for possible first-order autocorrelation. The method is illustrated by reference to a dental trial. PMID- 4027319 TI - Testing for qualitative interactions between treatment effects and patient subsets. AB - Evaluation of evidence that treatment efficacy varies substantially among different subsets of patients is an important feature of the analysis of large clinical trials. Qualitative or crossover interactions are said to occur when one treatment is superior for some subsets of patients and the alternative treatment is superior for other subsets. A non-crossover interaction arises when there is variation in the magnitude, but not in the direction, of treatment effects among subsets. Some authors use the term quantitative interaction to mean non-crossover interaction. Non-crossover interactions are usually of less clinical importance than qualitative interactions, which often have major therapeutic significance. A likelihood ratio test is developed to test for qualitative interactions. Exact critical values are determined and tabulated. PMID- 4027320 TI - Designing phase II studies in the context of a programme of clinical research. AB - Conventional statistical determinations of sample size in phase II studies typically lead to sample sizes of the order of 25 (Schoenfeld, 1980, International Journal of Radiation Oncology, Biology and Physics 6, 371-374). When the development of new treatments is proceeding rapidly relative to the recruitment of suitable patients, such requirements can prove to be too demanding. As a result, either sample sizes are reduced by a rather arbitrary weakening of the risk specifications, or certain new treatments go untested. In this paper, the phase II testing of a number of treatments will be considered as a single study which has the objective of identifying the most promising treatment for phase III investigation. It is seen to be advantageous to test more treatments, with fewer subjects receiving each, than the conventional methods would allow. PMID- 4027321 TI - Estimation for a model of multiple malaria infections. AB - The Macdonald-Dietz model for superinfection in malaria is a time-dependent infinite-server queue. However, the queue is only partially observable; it can be ascertained only as not empty or empty. Moreover, continuous observation of the queue is impossible. This paper derives likelihoods for the model's parameters with incomplete, multiwave panel data, and numerically maximizes those likelihoods for some data from a field study in Nigeria. PMID- 4027322 TI - The ML estimation and testing of generalized ABO-like data with no observed double recessives. AB - The general method of the discrepancy or heterogeneity chi-square is applied to ABO-like data in which there are no observed double blanks in either the disease or the control group. When the recessive gene frequency is assumed zero, this method leads to an approximate chi-square test identical to that suggested by Smouse and Williams (1982, Biometrics 38, 757-768). When this assumption is relaxed, there arise two cases which are determined by whether the maximum likelihood estimate of this frequency is zero or not. It is shown that the value of the simple score statistic of Gart and Nam (1984, Biometrics 40, 887-894) discriminates between the two cases. The various omnibus test statistics for comparing groups are shown to differ little in several practical examples. However, under the more general assumption the appropriate degrees of freedom is one more than the number previously suggested. PMID- 4027323 TI - Estimation of a derivative by a difference quotient: its application to hepatocyte lactate metabolism. AB - Values of the derivative of a convex function are estimated from data for the function by assigning the difference quotients of the observations to appropriate values of the determining variable. The procedure is illustrated for the time course of hepatocytes incubated with lactate, of amount l, for which pyruvate, of amount p, is also observed. An empirical linear relation between dp/dt and ln(l/p) is established. PMID- 4027324 TI - Investigating maximum power losses in survival studies with nonstratified randomization. AB - In studies with nonstratified randomization, imbalances may occur which lead to power loss. We investigate how much power may be lost at worst, that is, with small but nonnegligible probability. The situation considered is a two-treatment trial with censored survival data, and three to five strata. We also derive asymptotic results, as the sample size and/or number of strata increase. In addition, we consider how much a projected sample size needs to be increased to be confident (at a certain probability level) that the intended power will be retained, conditionally on the unbalanced configuration. PMID- 4027325 TI - Analysis of incomplete multivariate data from repeated measurement experiments. AB - This paper analyses two sets of data that consist of repeated measurements with missing data. The missing observations always occur at the end of the series of repeated measurements. The score test for multivariate normal data is used to compare treatment groups; if the original data are not multivariate normal they are replaced by expected normal scores. PMID- 4027326 TI - On the problem of measuring the distance between distribution functions: analysis of hospitalization versus mortality. AB - The relationship between hospitalization, as a measure of morbidity, and mortality is examined. The difference between age at hospitalization in a general medical department and age at death in Oslo, Norway, is studied. The problem is transferred to the one of examining the difference between two cumulative distribution functions F and G. For this purpose, a quantile distance function based on the inverses of the distribution functions is applied. We give the natural estimate of the quantile distance function, and some asymptotic properties of the corresponding empirical process. For the particular situation where one of the distribution functions is known, a confidence band for the quantile distance function is derived. Applying these results, we show that there are reasons to believe that age at hospitalization and age at death are equally distributed, apart from a constant shift. PMID- 4027327 TI - Efficiency of age-adjusted tests in animal carcinogenicity experiments. AB - Carcinogenicity experiments may be analysed by a simple comparison of the control and exposed groups with respect to the proportions of observed tumors amongst dead animals, when longevity is identical in control and exposed groups. This simple-proportions test is invalid when longevity varies between groups and age adjusted methods such as the Hoel-Walburg or logrank test are needed. This paper stresses that there is an advantage to using age-adjusted tests, even when the simple-proportions test is valid. The argument is based on calculations of the asymptotic relative efficiency of the simple-proportions test with respect to both the Hoel-Walburg and the logrank tests. PMID- 4027328 TI - Assessment of interaction between carcinogens in long-term factorially designed animal experiments. AB - Two substances interact if the combined action results in an effect which is greater than, or less than, that of the sum of the effects produced separately by the substances. Finney (1971, Probit Analysis, 3rd ed. Cambridge: Cambridge University Press) proposed a probabilistic model for simple independent action of two substances for the case of dichotomous outcomes. Using Finney's underlying model, we examine tests for interaction between carcinogens or toxic substances for data from long-term 2 x 2 and 2 x 2 x 2 factorially designed animal experiments. The outcome of interest is the occurrence or not of a certain event (for example, the appearance of a tumor) and the time at which the event occurred. The proposed tests are based on the proportional hazards model. We discuss some simple methods for checking the appropriateness of the proportional hazards assumption. Applications of the tests are made to data from a 2 x 2 and a 2 x 2 x 2 experiment. PMID- 4027329 TI - Estimating treatment effects in clinical trials subject to regression to the mean. PMID- 4027330 TI - On testing for bioequivalence. PMID- 4027331 TI - Condensation of DNA by the C-terminal domain of histone H1. A circular dichroism study. AB - The condensation of DNA by the C-terminal domain of histone H1 has been studied by circular dichroism in physiological salt concentration (0.14 M NaF). As the intact H1 molecule, its C-terminal domain induces the so-called psi state of DNA that is characterized by a nonconservative circular dichroism spectrum which is currently attributed to ordered aggregation of the DNA molecules. On a molar basis, intact H1 and its C-terminal domain give spectra of similar intensity. Neither the globular domain of H1 nor an N-terminal fragment, that includes both the globular and N-terminal domains, has any effect on the conservative circular dichroism of DNA. From these results it is concluded that the condensation of DNA mediated by histone H1 is mainly due to its C-terminal domain. The effect of the salt concentration and the size of DNA molecules on the circular dichroism of the complexes are also examined. PMID- 4027332 TI - Interaction of paired homologous series of diacridines and triacridines with deoxyribonucleic acid. AB - Viscometric measurements using covalently closed circular DNA and sonicated rod like DNA fragments were performed to investigate unwinding and extension of the DNA helix associated with binding of paired homologous series of diacridines and triacridines. The maximum interchromophore distance for members of the diacridine series spans from 15.1 to 27.5 A, permitting the largest of these ligands to cover up to 4 or 5 base-pairs, allowing for helical twist and local unwinding in a bisintercalated complex lacking severe bending or kinking of the DNA backbone. Helix unwinding angles and increments in DNA contour length are characteristic of bifunctional reaction for all the diacridines studied, the DNA lattice appearing to saturate with one ligand molecule bound per 4 base-pairs. The triacridines, whose maximum end-to-end interchromophore distances are the same as those of their paired diacridines, have maximum central-to-terminal interchromophore distances covering the range 7.5-13.8 A and thus have the potential to form trisintercalated complexes with one or two base-pairs sandwiched between each chromophore. However, helix extension and unwinding parameters for the triacridines are similar to those of the diacridines, and we find no evidence of a transition from bifunctional to trifunctional reaction as the homologous series is ascended. In general, the binding site size appears to be 5 base-pairs for the triacridines. The stereochemical requirements for trisintercalation of triacridines are discussed with reference to the present findings and to the work of others. PMID- 4027333 TI - The effect of histone H1 on the compaction of oligonucleosomes. A quasielastic light scattering study. AB - The structural properties of H1-depleted oligonucleosomes are investigated by the use of quasielastic laser light scattering, thermal denaturation and circular dichroism and compared to those of H1-containing oligomers. To obtain information on the role of histone H1 in compaction of nucleosomes, translational diffusion coefficients (D) are determined for mono-to octanucleosomes over a range of ionic strength. The linear dependences of D on the number of nucleosomes show that the conformation of stripped oligomers is very extended and does not change drastically with increasing the ionic strength while the rigidness of the chain decreases due to the folding of linker DNA. The results prove that the salt induced condensation is much smaller for H1-depleted than for H1-containing oligomers and that histone H1 is necessary for the formation of a supercoiled structure of oligonucleosomes, already present at low ionic strength. PMID- 4027334 TI - Torsional dynamics and rigidity of fractionated poly(dGdC). PMID- 4027335 TI - Deformational dynamics and NMR relaxation of supercoiled DNAs. PMID- 4027336 TI - Sequence-dependence of secondary structure formation: conformational studies of host-guest peptides in alpha-helix and beta-structure supporting media. PMID- 4027337 TI - Conformational properties of Pro-Pro sequences. I. Crystal structures of two dipeptides with L-Pro-L-Pro and L-Pro-D-Pro sequences. PMID- 4027338 TI - An A-helix structure for poly(dA-dT) X poly(dA-dT). PMID- 4027339 TI - Raman spectrum of a closed-circular DNA. PMID- 4027340 TI - Conformation of cyclic analogs of enkephalin. III. Effect of varying ring size. PMID- 4027341 TI - Determination of NOE "silent" dipolar interactions between magnetically equivalent nuclei: application to poly(dA).poly(dT). PMID- 4027342 TI - Effect of anisotropic bending rigidity and finite twisting rigidity on statistical properties of DNA model filaments. PMID- 4027343 TI - Vibrational circular dichroism of polypeptides. IV. Film studies of L-alanine homo-oligopeptides. PMID- 4027344 TI - Direct evidence for antifreeze glycoprotein adsorption onto an ice surface. PMID- 4027345 TI - Energetics of multihelix interactions in protein folding: application to myoglobin. PMID- 4027346 TI - Differential scattering of circularly polarized light by chromatin modeled as a helical array of dielectric ellipsoids within the born approximation. PMID- 4027347 TI - Random-phase calculation of the low-energy circular dichroism in glucans. PMID- 4027348 TI - The outcome of bacterial infection in subjects with benign familial leukopenia (BFL). AB - Benign familial leukopenia (BFL) is a hereditary phenomenon, encountered in several ethnic groups. Subjects bearing BFL are believed to be affected by bacterial infection in no greater incidence than normal subjects. In our study we investigated a group of subjects with BFL during an acute bacterial infection in comparison to subjects without BFL with the same infection. We found that the subjects with BFL had no absolute leukocytosis during the infection. Nevertheless, they reacted similarly to the other subjects in regard to their temperature and heart rate; however, they were hospitalized for fewer days than subjects without BFL. We conclude that BFL is a benign phenomenon, requiring neither specific treatment as such, nor more aggressive therapy during infection. The benign course of an acute bacterial infection in BFL indicates that perhaps the number of WBC's that are normally recruited during an infection in normal subjects highly exceeds that which is necessary. PMID- 4027349 TI - [Risk of vertebral fracture after menopause: identification of subjects at high risk by dual photon absoprtionometry]. AB - Dual photon absorptionometry of bone is used to detect in an exposed population those subjects who are high risk of fracture and also to follow up the evolution of these patients. 37 women who have suffered fractures have been compared to 41 women without fractures of similar age distribution. A highly significant correlation between body height and Bone Mineral Content (BMC) of the lumbar spine is found in the control group thus allowing the calculation of the expected BMC value for each patient. A crushing index is defined as the ratio of the observed BMC value to the expected one. Using this index, instead of the two more usual modes of BMC expression, leads to an improvement of the predictive estimation of fracture risk. The predictive value of such indices should still be improved. With this aim, further determinations of indices are desirable. The following requirements should be borne in mind: The physical data should be easily obtainable e.g. body height and weight and the meaning of the index based on these easily verifiable factors they should be easily understood. PMID- 4027350 TI - Loop diuretics may fail to inhibit (Na+, K+, Cl-) 'cotransport' in human red cells. AB - The inhibition of passive K+ influx into human red blood cells (RBC) by loop diuretics was found to be dependent on the external Na+ concentration. In the absence of external Na+, there was minimal inhibition but the influx remained dependent on Cl- ions. Thus, raising the external Na+ concentration increased the affinity of the putative (Na+, K+, Cl-) cotransport system in human RBC for loop diuretics. PMID- 4027351 TI - Changes in kidney transaminase activity during development in male and female rats. AB - The developmental changes in the activity of kidney transamidinase in male and female rats were investigated. The activity in both sexes increased rapidly after birth, reaching adult levels at 4 days of age. After weaning, the activity in male rats remained constant, while in female rats it declined to 60% of that in males. Thus, transamidinase is in the neonatal cluster of enzyme differentiation. PMID- 4027352 TI - Preferential uptake of intravenously administered hyaluronidase (Hyalosidase) by damaged rat myocardium. AB - The induction of myocardial infarction in rats by ligation of the left-anterior coronary artery was confirmed by measurement of increased plasma levels of creatine kinase, aspartate aminotransferase and lactate dehydrogenase. Using this model system it has been established that intravenous administration of 125I labelled hyaluronidase to rats resulted in a preferential uptake of the enzyme by damaged myocardium as compared to normal heart tissue. PMID- 4027353 TI - The effect of different hyperglucagonemic states on monooxygenase activities and isozymic pattern of cytochrome P-450 in mouse. AB - The continuous infusion of a low dose of glucagon (35 micrograms/kg/d, for 5 d) constitutes, in view of glucose-6-phosphatase and phosphoenolpyruvate carboxykinase activities, a reliable experimental model of hyperglucagonemia. By conjunction of monooxygenase assays and immunoquantitation of specific isozymes of cytochrome P-450, the actual inducing ability of glucagon has been shown and it might explain some of the modifications of the drug metabolizing system in diabetic mice. The isozymic pattern of cytochrome P-450 of liver microsomes from diabetic mice appears very different from that produced by classical inducers. PMID- 4027354 TI - Monoclonal antibodies to human plasma protein X alias complement S-protein. AB - Protein X alias complement S-protein was isolated by dissociation from purified XC5b-9 (fluid-phase terminal C5b-9) complexes with 250 mM deoxycholate and subsequent sucrose density gradient centrifugation and Sephacryl gel chromatography. Polyclonal rabbit and monoclonal mouse antibodies were used to preliminarily characterize the protein in human serum and plasma. In plasma, Protein X yielded a symmetrical immunoprecipitate of alpha 2-mobility in a crossed immunoelectrophoresis assay. However, a second immunoprecipitate of alpha 1-mobility was observed when serum was analysed; this precipitate represented Protein X in complex with antithrombin-III. The co-precipitation of Protein X with serum antithrombin-III was exploited for establishing a simple screening test for unequivocal identification of monoclonal anti-Protein X antibodies. SDS PAGE immunoblotting with monoclonal antibodies showed that Protein X exhibits pronounced microheterogeneity, migrating as a diffuse moiety of approx. Mr 80-90 000. Additionally, a small amount of polymeric aggregates appear to be present in plasma. Reduction of disulfide bonds led to liberation of a polypeptide of approx. 15 K as discerned by two-dimensional SDS-PAGE immunoblotting. Protein X is not cleaved to lower molecular weight entities during the process of blood coagulation or during formation of fluid-phase terminal complement complexes. The plasma concentrations in healthy adults were in the range of 500-700 micrograms/ml. The availability of methods for isolating Protein X and raising monoclonal antibodies will facilitate further studies on the dual role of this protein in the terminal complement and coagulation cascades. PMID- 4027355 TI - Solid phase synthesis. Nobel lecture, 8 December 1984. PMID- 4027356 TI - The amino acid sequence of human sperm protamine P1. AB - Human sperm protamines have been extracted from spermatozoa pooled from several donors, converted to their S-pyridylethylated derivatives and resolved into two major components, P1 and P2, by Bio-Rex 70 chromatography. Protamine P1 was further purified by Bio-Gel P-10 chromatography and sequenced directly on a gas phase protein sequencer for 43 residues. To complete the sequence, P1 was cleaved at methionine 36 and the C-terminal tetradecapeptide was purified by h.p.l.c. and sequenced completely. The 50 residue sequence is: (sequence see text) This sequence has a calculated molecular weight of 6674 and is homologous with four other published mammalian protamine sequences. PMID- 4027357 TI - Shape transformation of erythrocyte ghosts depends on ion concentrations. AB - Resealed human erythrocyte ghosts undergo shape transformations similar to those of intact erythrocytes. The results indicate that the shape of these ghosts depends on the inner as well as on the outer NaCl concentration. A correlation between shape and calculated transmembrane potential was established similar to that for intact human erythrocytes. PMID- 4027358 TI - Influence of the intracellular and extracellular cation concentration on monovalent cation efflux of resealed human erythrocyte ghosts. AB - Tracer efflux measurements (86Rb+ and 22Na+) were performed on resealed human erythrocyte ghosts at different intra- and extracellular NaCl concentrations. Using a modified Goldman equation the observed alterations of the rate constants could be explained by taking into account the transmembrane and surface potentials, at constant permeability coefficient. These results emphasize the importance of membrane surface potentials in triggering ion transport across biological membranes. PMID- 4027359 TI - Impaired muscle glucose metabolism in acute renal failure. AB - Renal failure is associated with peripheral insulin resistance and consequent carbohydrate intolerance. This report investigates carbohydrate metabolism in vitro in epitrochlearis and hemidiaphragm muscles taken from acutely uraemic and sham-operated rats. Muscles from acutely uraemic rats (compared to those from sham-operated rats) incubated with 5 mM glucose showed increased rates of basal and insulin-stimulated glycolysis and glycogen turnover, but pyruvate dehydrogenase and tricarboxylic acid-cycle flux was not increased in uraemia. Glycolysis (but not glycogen turnover) in muscles from acutely uraemic rats tended to show decreased responsiveness to stimulation by insulin. It is concluded that acute uraemia is associated with a defect(s) in muscle that produces intrinsic insulin resistance and results in diversion of glucose (both in basal and insulin-stimulated states) from glycogen synthesis into glycolysis. PMID- 4027360 TI - [Mechanical tension in different parts of the left ventricle of the heart exposed to inotropic factors]. AB - A study was made of the effects of different inotropic factors on mechanical tension in the left ventricular wall and in the apex of the heart and of the participation of these regions in the formation of hemodynamic characteristics. Adrenaline caused similar effects whereas CaCl2 exerted different inotropic effects on the left ventricular wall and the apex of the heart. Changes in mechanical tension of the wall correlated with variations in the pressure inside the left ventricle. Tension in the apex of the heart produced alterations in the stroke volume. PMID- 4027361 TI - [Inactivation of the postural asymmetry factor at the stage of compensation for the postural disorder induced by unilateral removal of the motor area]. AB - The peptide nature of the posture asymmetry factor (PAF) produced in the brain after unilateral removal of the motor region of the neocortex was established. The inactivation of PAF activity in the brain toward the end of the third week after the removal is due to PAF inactivation by the endogenous factor absent from the intact brain. The molecular weight of the inactivation factor exceeds 5.0 kD that makes it possible to separate it from the PAF by gel filtration on Sephadex G-25. The correlation was marked between the increasing activity of the PAF inactivation factor and the recovery of the initial symmetric functioning of the spinal centers during three weeks after unilateral damage to the CNS. PMID- 4027362 TI - [Adenylate cyclase activity of the gastric mucosa and the morphological changes in the gastrointestinal tract in the experimental reproduction of duodenal ulcers with subsequent truncal vagotomy]. PMID- 4027363 TI - [Protection of long-term ischemic kidneys from the damages of reoxygenation by using the temporary inhalation of a gas hypoxic mixture]. AB - Experiments were carried out on 240 August and Wistar rats. It was shown that renal reperfusion after 2 h of ischemia, performed following 24-hour inhalation by the animals of a gas hypoxic mixture (GHM) with 10 to 12% O2, increased the survival rate of the rats and accelerated the resynthesis of adenine nucleotides by the kidneys as compared with analogous characteristics during reperfusion paralleled by inhalation of air or oxygen. The protective effect of GHM inhalation on renal function and metabolism was approximately the same as the protective action of high doses (240 mg/kg) of the antioxidant ionol. The experiments confirm the role of lipid peroxidation in the pathogenesis of reoxygenation injuries and the protective effect of GHM inhalation in the early period of reperfusion. PMID- 4027364 TI - [Changes in the number of Ec cells in the small intestine and the serotonin level in the blood plasma of fasting rats]. AB - A study was made of the amount of Ec-cells in the small intestine mucosa and blood plasma serotonin of rats in health and fasting. It was established that 24 hours after food deprivation the amount of Ec-cells rises approximately 2-fold as compared with control. The cells demonstrate the intensification of the argentaffin reaction. The content of serotonin in blood plasma increases 2-fold accordingly. On day 3 of fasting the amount of Ec-cells and intensity of the argentaffin reaction decrease to normal, whereas the content of blood plasma serotonin does not change essentially. This may be linked with a massive release of serotonin to blood and depletion of Ec-cells because of which the threshold of their histochemical demonstration is reduced. On day 7 of food deprivation the amount of Ec-cells and the intensity of the argentaffin reaction increase again but the serotonin content dramatically falls down. This phenomenon may be related to the derangement of serotonin release to blood or to the transformation from the synthesis of serotonin to the synthesis of some other hormone, most likely melatonin. PMID- 4027365 TI - [Characteristics of the regulation of the blood stroke volume in rat pups developing under hypokinesia and muscle training]. AB - In the early postnatal period, high motor activity of young rats leads to an increase in the tonic effects of the sympathetic nerves and to a decrease in that of the vagus on the systolic blood volume. PMID- 4027366 TI - [Effect of caffeine on active Ca2+ ion transport in a homogenate of skeletal muscles and myocardium]. AB - A Ca2-selective electrode was used to study active transport of Ca2+ by sarcoplasmic reticulum fragments of rabbit skeletal muscle and myocardium homogenates. The specific Ca2+ transport activities (mumol Ca2+/min/mg tissue) are 40 = 60 and 3 = 5 units for fast and slow muscles and the myocardium, respectively. Caffeine (5 mM) exerts a powerful inhibitory influence on Ca2+ transport in skeletal muscle homogenates. For fast muscles, the degree of inhibition exceeds 50%. The rate of Ca2+ transport in the myocardium homogenate increases in the presence of creatine phosphate. The latter produces no effect on Ca2+ transport in skeletal muscle homogenates. The high sensitivity of Ca2 transport to caffeine, a specific blocker of Ca2+ transport to the terminal cisterns of the sarcoplasmic reticulum, suggests that the terminal cisterns, apart from being a reservoir for Ca2+ needed for contraction trigger, may play an essential role in muscle relaxation. PMID- 4027367 TI - [Identification of pro-opiomelanocortin and the secretion of its peptide fragments in the adrenals of the bull]. AB - Immunoreactive alpha-, beta- and gamma-endorphins and beta-lipotropin--C-terminal peptide fragments of pro-opiomelanocortin (POMC)--were discovered and measured by RIA in the bovine adrenal medulla and cortex. These peptides were also discovered in perfusates of the adrenal gland. POMC proper and some intermediate forms of its processing not differing in electrophoretic mobility from the respective molecular forms of hypophyseal POMC were identified in the medulla and cortex of the adrenals by the immunoblotting technique with the use of antiserum to beta lipoprotein. It is concluded that POMC gene is expressed in the adrenal medulla and cortex and that as a result of POMC processing a noticeable amount of its peptide fragments is formed and secreted in adrenal cells. The authors thus suggest the presence of existence of the pituitary-unrelated mechanisms of adrenal function control with participation of POMC peptides synthesized in the adrenals. PMID- 4027368 TI - [Formation of alpha-tocopherol complexes with phosphatidic acid]. AB - High-resolution 1H-nmr spectroscopy and UV spectrophotometry have demonstrated the formation of alpha-tocopherol and phosphatide acid complexes. The complex formation occurs at the expense of two types of interactions: polar interaction of the OH-group of alpha-tocopherol with a keto group of phosphatide acid and hydrophobic interaction of the methyl groups of the chroman nucleus of alpha tocopherol with cis-unsaturated double bonds of the accyls of phosphatide acid. The role of such complexes in the mechanisms of biomembrane stabilization for preventing the damaging action of phospholipases is discussed. PMID- 4027369 TI - [Unusual estrogen-binding liver protein in rats and the metabolism of sex steroids]. AB - A study was made of the effect of a highly purified preparation of an unusual estrogen-binding protein (UEBP) of rat liver on 3H-estradiol (3H-E2) and 3H testosterone (3H-T) metabolism by female rat liver homogenates. The UEBP decreased the rate of metabolic conversions of 3H-E2 and 3H-T in a dose-dependent and specific manner. The effectiveness of the inhibitory action of the UEBP declined with increase of metabolic activities of homogenate enzymes. The effects of the UEBP were reduced fully or partly by the ligands specifically binding to the UEBP, estrone (E1), and estriol (E3) respectively. The latter fact was used to demonstrate the effectiveness of the endogenous male rat liver homogenate UEBP in the control of 3H-E2 metabolism. The UEBP did not exhibit any oxidoreductase activity on the use of 3H-E1, 3H-E2, 3H-E2, 3H-T and 3H-androstenedione with NAD+, NADH, NADP+, and NADPH as cofactors. These data present the first direct experimental evidence of the regulatory function of the UEBP in the time course of changes in sex steroids. PMID- 4027370 TI - [Role of tricyclic antidepressants in the central regulation of hyperalgesia and stress analgesia]. AB - The effect of hypophysectomy (HE) on pain thresholds was studied in female noninbred rats. Hyperalgesia was observed after HE since the first till the sixth day of the observation period. Droperidol (1 mg/kg i.p.) and amitryptyline (5 mg/kg i.p.) produced hyperalgesia in sham-operated rats, which was potentiated in hypophysectomized animals. In rats taken into the experiment 3 days after operation, no increase in the pain threshold was recordable during the 30-minute painful stress, and poststress autoanalgesia did not develop subsequently. The opposing data were obtained in sham-operated animals. On intraperitoneal administration of phentanyl (25 micrograms/kg) after the 30-minute painful stress hypophysectomized rats did not manifest any potentiation of its analgesic effect in contradistinction to sham-operated animals. Simultaneous administration of phentanyl at the same dose and melipramine (5 mg/kg i.p.) produced considerable potentiation of analgesia if administered after stress. In hypophysectomized rats, that effect was somewhat reduced. PMID- 4027371 TI - [Characteristics of serotonin binding by the cells of immunocompetent tissues and synaptosomes]. AB - The ratio of surface and intracellular serotonin binding by the cells of immunocompetent tissues and synaptosomes of immunized and intact CBA mice was studied by treatment with imipramine inhibiting serotonin penetration through the cytoplasmic membrane. As early as 5 minutes after the antigen injection the content of intracellular amine increased with changes in its binding by the cytoplasmic membrane. The probability of the functional interconnection between the reaction of immunocompetent tissues to the antigen and two forms of serotonin binding by the cells of these tissues is discussed. PMID- 4027372 TI - [Temporal organization of the cellular reproduction processes in Ehrlich ascites tumor]. AB - Experiments were made on randombred male mice weighing 18-20 g maintained on the light regimen L:D-12:12. The animals were given a single injection i. p. of a hypotetraploid subline of Ehrlich's ascites tumor. Fluctuations in the number of mitotic cells and no changes in the number of DNA-synthesizing cells were established. This indicates that synchronization of tumor cells under these conditions occurs mainly in the G2 phase. The results of the present experiments confirm those obtained during previous investigations, showing the lack of the dependence of the cell proliferation pattern on the cell ploidy. The disturbance of the chronobiological organization of tumor cell proliferation that is manifested by upset synchronization of cell division and DNA synthesis is common to all Ehrlich's ascites tumor sublines under study. PMID- 4027373 TI - [Changes in arginase activity during neurinoma growth]. AB - Arginase activity was studied in the brain and other tissues of the rat at the different periods of neurinoma growth. The activity of the enzyme was considerably activated in the affected hemisphere on the 4th day, in the skin of the head and thigh on the 6th day after tumor transplantation. Elevation in arginase activity in the neoplasm itself was recorded on the 16th day. The data obtained point to the physiological significance of arginase during neurinoma growth. PMID- 4027374 TI - [Differing microsomal monoxygenase activity in the cells of ascitic and solid forms of transplantable tumors]. AB - Aryl hydroxylase activity has been demonstrated to depend on the pattern of tumor cell structural organization. The activity of microsomal monoxygenases in the ascitic forms of sarcoma MC-11, hepatoma 22a and Ehrlich's tumor was much lower than in the corresponding solid tumors. Aryl hydroxylase was activated after the animals received 3-MC, but the magnitude of the activity induced did not correlate with the basic activity in the different tumors. In in vitro experiments, 7,8-benzoflavone inhibited the enzyme in all the tumors, whereas metyrapone did not affect BP-hydroxylation. It is assumed that all the tumors investigated contain hemoprotein that is similar to cytochrome P1-450. PMID- 4027375 TI - [Stimulating action of endorphins on the development of sympathetic ganglia in culture]. AB - The effect of gamma-and beta-endorphins, leu- and met-enkephalins on the growth and differentiation of nervous tissue was studied in organotypic cultures of the sympathetic ganglia of newborn rats. The growth of explants in living cultures and preparations stained by the Holmes method was analyzed. It was established that endorphins are capable of stimulating the growth of neurites from the explant, of increasing the number of glial and fibroblastoid cells in the zone of the growth. The mean value of the maximal magnitude of the zone of the growth in normalcy was 464 +/- 136 micron, that on addition of leu- and met-enkephalins, gamma- and beta-endorphins 879 +/- 161, 900 +/- 160, 959 +/- 170, and 1056 +/- 137 microns. The growth effect induced by endorphins was demonstrated within a wide dose range--from 10(-7) to 10(-14) M. Naloxone did not inhibit the stimulant action of the peptides. It is suggested that opioid neuropeptides can be used as a source of nonspecific growth factors for nervous tissue. PMID- 4027376 TI - Surface phenotypes of human hemopoietic progenitor cells defined by monoclonal antibodies. AB - A panel of ten monoclonal antibodies which react with antigens present on the surface of myeloid leukemic cells was used to investigate the distribution of these antigens on normal hemopoietic stem cells and progenitor cells at various stages of maturity. A population of immature cells, possibly stem cells, that are capable of regenerating CFU-GM in long-term marrow cultures reacts with four antibodies recognizing antigens abundantly expressed in leukemic cells, but does not react with antibodies against Ia-like molecules or against carbohydrate determinants specific for myeloid cells. Progenitor cells that form mixed colonies in semisolid medium (CFU-GEMM), early erythroid (BFU-E) and early myelomonocytic (type 1 CFU-GM) progenitors retain the antigens present on the hypothetical stem cell population and begin to express Ia-like antigens. As they differentiate, myeloid and erythroid progenitors undergo a series of quantitative and qualitative shifts in surface phenotype. They begin to express stage-related, lineage-specific antigens and cease expressing antigens common to early cells of different lineages. The identification of antigens present on very immature normal progenitor cells should be valuable in future studies aimed at the detailed characterization of this relatively little-known hemopoietic cell population. PMID- 4027377 TI - Formation of a morphologically complex system by peroxidase-positive lysosomal elements in human monocytes. AB - Computer-aided three-dimensional reconstruction of serial ultrathin sections revealed that freshly prepared monocytes from human blood contained endogenous peroxidase (PO) not only in cytoplasmic granules, but also in long contorted tubules and in complex elements, which consisted of both tubular and granular components. The various PO-positive elements formed an intricate system, which was separate from all other cytoplasmic structures, including the endoplasmic reticulum and the Golgi apparatus. Because the PO-positive elements in monocytes are known to be primary lysosomes, which are involved in host defense mechanisms, we suggest that the antimicrobial functions of human blood monocytes are exerted by functionally and morphologically diverse subcompartments of a complex system rather than by separate uniform granules. PMID- 4027378 TI - SFL 23.6: a monoclonal antibody reactive with CFU-E, erythroblasts, and erythrocytes. AB - A cytotoxic (IgG2b) monoclonal antibody (McAb) for a novel erythroid differentiation antigen was generated by hyperimmunizing young mice with mononuclear cells obtained from livers of 20- to 22-week-old fetuses. This McAb, designated SFL 23.6, shows an extremely well-defined reactivity with the cells of the erythroid lineage at all stages of maturation as evident from the labeling of morphologically identifiable erythroid precursors and of erythrocytes present in peripheral blood, bone marrow, and fetal liver, and from its reactivity with culture-derived erythroblasts. The nonerythroid cells present in these and other tissue preparations were not labeled by SFL 23.6. The erythroid lineage specificity of McAb SFL 23.6 was confirmed by a cell-sorting experiment in which 97% of the cells in the fluorescent fraction sorted from SFL 23.6-treated bone marrow cells were erythroid precursors at various stages of maturation. Complement-mediated cytotoxicity and progenitor cell-sorting experiments showed that most (greater than 90%) of the late erythroid progenitors (CFU-E) and only a small proportion of the early erythroid progenitors (BFU-E) express the antigenic determinant identified by SFL 23.6. The myeloid progenitors (CFU-GM) and multilineage progenitors (CFU-GEMM) were negative for the SFL 23.6 antigenic determinant. The antigen recognized by SFL 23.6 has not been determined as yet. Because of the pattern of its reactivity and its dependence on sialic acid residues, the possibility of its relationship to glycophoria A was entertained. However, previous work using antiglycophorin McAbs (R-10) has shown that this determinant is not expressed in CFU-E. Therefore, among the erythroid lineage specific McAbs described thus far, SFL 23.6 is unique in its reactivity with CFU E and the mature erythron. Reagents with such specificity may be useful in studies of erythroid differentiation and commitment. PMID- 4027380 TI - In vitro analysis of the homing properties of human lymphocytes: developmental regulation of functional receptors for high endothelial venules. AB - Circulating lymphocytes leave the blood by binding to specialized high endothelial cells lining postcapillary venules in lymphoid organs or sites of chronic inflammations, migrating through the vessel wall into the surrounding tissue. The capacity of lymphocytes to recognize and bind to high endothelial venules (HEVs) is thus central to the overall process of lymphocyte traffic and recirculation. We show that viable human lymphocytes bind selectively to HEVs in frozen sections of normal human lymph nodes, thus defining a simple in vitro model for the study of human lymphocyte homing properties. Optimal conditions for the quantitative analysis of lymphocyte-HEV interaction are described. Furthermore, by using this assay, we demonstrate that the ability of human lymphocyte populations to bind to HEVs parallels their presumed migratory status in vivo. Thus, thymocytes and bone marrow cells, which are sessile in vivo, bind poorly to HEVs in comparison with mature circulating lymphocytes in peripheral blood or in peripheral lymphoid tissues. These results indicate that HEV-binding ability is a regulated property of mature lymphocytes and, as demonstrated previously in animal models, probably plays a fundamental role in controlling lymphocyte traffic in humans. The in vitro model of lymphocyte-HEV interaction thus provides a unique means to assay the migratory properties of normal and neoplastic human lymphocyte subsets, to analyze the role of lymphocyte traffic mechanisms in normal and pathologic inflammatory reactions, and to define some of the molecular mechanisms responsible for the control of lymphocyte migration and positioning in humans. PMID- 4027379 TI - Megakaryocyte interaction with subendothelial extracellular matrix is associated with adhesion, platelet-like shape change, and thromboxane A2 production. AB - We have examined the morphological and secretory behavior of rat and guinea pig megakaryocytes exposed for up to 24 hours to extracellular matrix produced by cultured bovine endothelial cells. By phase-contrast microscopy of living cells and in more detail by scanning electron microscopy, the megakaryocytes showed a nonreversible adherence, an extensive formation of filopodia around the periphery like the rays of the sun, and a tendency toward flattening. These filopodia were generally linear with attenuated tips and were larger than, but resembled the filopodia of, rat or guinea pig platelets exposed to this extracellular matrix. In contrast, isolated megakaryocytes on glass or on uncoated plastic surfaces did not show these responses; adherence, in the face of gentle agitation before fixation, was minimal, with rare filopodia and no flattening. Megakaryocytes that interacted with the extracellular matrix produced significant amounts of thromboxane A2, but this did not occur on uncoated surfaces and could not be attributed to other contaminating cells in the megakaryocyte suspensions. The appearance in megakaryocytes of these typical platelet responses indicates that megakaryocytes acquire the functional capabilities of platelets by the synthesis and assembly of platelet substances and organelles. Thromboxane production by megakaryocytes stimulated by the extracellular matrix is a readily quantifiable measure of this capacity. PMID- 4027381 TI - The influence of estrogen and prolactin on Hageman factor (factor XII) titer in ovariectomized and hypophysectomized rats. AB - The synthesis of prothrombin in hepatic microsomes is augmented in intact estrogen-treated rats and in hypophysectomized rats treated with purified prolactin. We investigated the influence of these gonadal and pituitary hormones on the titer of Hageman factor (factor XII), reportedly elevated in women using oral contraceptives. Rats were ovariectomized to minimize the influence of endogenous estrogen and progesterone on the Hageman factor titer. The administration of progesterone did not alter the plasma concentration of Hageman factor. In contrast, the infusion of 17 beta-estradiol induced a marked elevation of the plasma Hageman factor titer, as measured functionally and immunologically. The titer of Hageman factor was directly related to both plasma estradiol and prolactin concentrations, indicating that prolactin may play a role in the regulation of plasma Hageman factor titers. In agreement with this, hypophysectomy induced a marked decrease in the Hageman factor level. In hypophysectomized ovariectomized animals, the administration of estradiol restored the Hageman factor titer to normal levels, whereas the infusion of prolactin induced a dramatic rise in the Hageman factor titer to the degree observed in nonhypophysectomized estrogen-treated rats. No further increase in the Hageman factor titer was observed in rats treated with both estradiol and prolactin. These data indicate that estrogens increase the plasma Hageman factor titer both directly and through its release of prolactin and that prolactin may also increase the titer of Hageman factor through estrogen-independent mechanisms. PMID- 4027382 TI - Surface membrane glycoproteins of wild-type and differentiation-inducer-resistant HL-60 cells. AB - Surface membrane glycoproteins (SMGs) of cells from the parental wild-type HL-60 cell line and from three sublines variably cross-resistant to the granulocyte differentiation-inducing effects of retinoic acid (RA), dimethylsulfoxide (DMSO), and certain purine bases (6-thioguanine [6TG] or hypoxanthine) were studied by one-dimensional and two-dimensional gel electrophoresis. After both oligosaccharide (periodate/borotritide) and peptide (1,3,4,6-tetrachloro-3 alpha, 6 alpha-diphenylglycouril) ectolabeling procedures, striking common changes were noted in the gel electrophoretic patterns of the SMGs from the RA- and 6TG resistant sublines compared to those from the wild-type HL-60 line or the DMSO resistant subline. Most prominently, this included the presence in the RA- and 6TG-resistant cells of an apparent high molecular weight acidic glycoprotein(s) (mol wt, 200 to 285 kilodaltons [kD]; isoelectric point range [pl], 4.5 to 6.0) not observed in the wild-type or DMSO-resistant cells and, conversely, the presence of a lower molecular weight glycoprotein(s) (mol wt, 120 to 165 kD; pl, 4.2 to 5.9) in the wild-type and DMSO-resistant cells, which was absent or much reduced in the RA- and 6TG-resistant cells. These acidic SMGs did not change as a function of the induction of granulocyte differentiation. However, some other more basic SMGs varied as a function of granulocyte differentiation in both the wild-type and differentiation inducer-resistant sublines, including the loss of the transferrin receptor and the gain of a mol wt 55- to 60-kD neutrophil associated protein. In the context of previously reported information, these results indicate (1) that the overall pattern of SMG changes in the RA- and 6TG resistant cells closely resembles that associated with multidrug (pleiotropic) resistance to cytotoxic agents in a variety of mammalian cells; (2) that the RA/6TG resistance-associated SMG changes are not granulocyte differentiation stage-specific; and (3) that either the RA/6TG resistance-associated SMG changes are not related to the resistance mechanism or they are involved in the resistance/cross-resistance mechanism(s) for RA/purine bases but not for DMSO. PMID- 4027383 TI - Aggressive non-Hodgkin's lymphomas in immunocompromised homosexual males. AB - During the period from 1981 through 1984, 14 immunocompromised homosexual males with intermediate or high-grade non-Hodgkin's lymphoma were seen at University of Texas M.D. Anderson Hospital and Tumor Institute. Six patients had diffuse large cell lymphoma, seven had diffuse undifferentiated lymphoma, and one had unclassifiable lymphoma that suggested large-cell lymphoma. Eight patients had the acquired immunodeficiency syndrome (AIDS) and five had the AIDS-related complex. Kaposi's sarcoma was initially present in four patients and developed later in two others. The patients with diffuse large-cell lymphoma were characterized by more severely altered immune parameters, multicentric brain mass lesions, pretherapy opportunistic infections, lower performance status, poor response to therapy, and death in all within six months. The undifferentiated lymphoma group had preceding generalized reactive lymphadenopathy, less severe immune dysfunction, and excellent response to combination chemotherapy, with survival time greater than 19 months in three patients. Twelve of the patients had extranodal sites of lymphoma at presentation. There is a definite trend for the development of aggressive non-Hodgkin's lymphomas with unusual sites of extranodal involvement in immunocompromised homosexual males, with the potential for good tolerance to combination chemotherapy and improved survival in the subgroup without severe concomitant opportunistic infections. PMID- 4027384 TI - Potentiality of the murine colony-forming cells detected by an in vivo diffusion chamber culture system. AB - Culture of a mixture of bone marrow cells with and without T6 chromosome marker in diffusion chambers in mice yielded colonies (CFU-DG) containing cells of a single karyotype, suggesting clonality. Injection of individual CFU-DG colonies into lethally irradiated mice resulted in increased spleen colony formation on day 12 (CFU-S). The possibility of endogenous origin was excluded by demonstrating the presence of T6 marker in both CFU-DG and CFU-S colonies in karyotypically normal hosts. These findings suggest that the cells giving rise to granulocytic colonies in diffusion chambers also can give rise to multipotential hemopoietic cells. PMID- 4027386 TI - Sp alpha I/65: a new variant of the alpha subunit of spectrin in hereditary elliptocytosis. AB - Two molecular defects involving the spectrin heterodimer (SpD) contact site of the alpha chain (the alpha I domain) were previously identified using limited tryptic digestion followed by two-dimensional isoelectric focusing/sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Both are characterized by atypical peptide maps which reveal a marked decrease of the 80,000-dalton alpha I domain and a formation of new major peptides of either 74,000 (Sp alpha I/74) or 46,000 (Sp alpha I/46) daltons. We now report a third variant of the spectrin alpha chain, designated Sp alpha I/65, in three unrelated black families. In all three probands, the percentage of SpD in the low ionic strength (O degrees C) membrane extracts was increased to 19% to 32%. One- and two-dimensional electrophoretic separations of limited tryptic digests of spectrin from all three probands revealed a decrease of the alpha I domain of spectrin and the concomitant appearance of peptides at 65,000 daltons and isoelectric points ranging from 5.2 to 5.3. The abnormal 65,000-dalton peptides could be stained with an antiserum which had been raised against the alpha I domain, indicating that it was derived from the alpha I domain. PMID- 4027385 TI - Hereditary nonspherocytic hemolytic anemia due to a new hexokinase variant with reduced stability. AB - A 27-year-old woman with severe chronic hemolytic anemia was found to have reduced red cell hexokinase activity when the degree of reticulocytosis was considered. This enzyme had normal pH-dependent activity, normal Km for glucose, fructose, and mannose, normal Km for Mg adenosine triphosphate (ATP)2- and Ki for glucose-1,6-diphosphate. Furthermore, the pH-dependence and orthophosphate dependence of Ki for glucose-1,6-diphosphate were normal. However, this hexokinase was inactivated rapidly at 44 degrees C. No abnormalities were found in the red cell hexokinase isozymic pattern when it was compared with the profile obtained from cells of similar age. The hexokinase specific activity was reduced in all the red blood cell fractions obtained by density gradient ultracentrifugation; a marked difference in the distribution of cells through the gradient was evident. Among the glycolytic intermediates, a significant decrease of 2,3-diphosphoglycerate was evident. ATP and glucose 6-phosphate were also reduced when compared with cells of similar. Glucose consumption of the hexokinase-deficient cells decreased, but the rate of glucose metabolized through the hexose monophosphate shunt was unchanged. Although the total hexokinase activity in lymphocytes was only reduced by 37%, a marked hexokinase deficiency was detected in blood platelets (20% to 25% of normal activity). The parents and one of two siblings of the patient were heterozygous for the defect, with 66% to 74% of normal erythrocyte hexokinase activity and reduced heat stability of the enzyme. These results, when compared with those obtained in previously reported cases of hexokinase deficiency, provide further evidence of the broad phenotypic variability that characterizes this disorder. Furthermore, it is suggested that failure of energy generation is probably the primary cause of hemolytic anemia in hexokinase deficiency. PMID- 4027387 TI - Diadenosine 5',5'''-p1,p4-tetraphosphate deficiency in blood platelets of the Chediak-Higashi syndrome. AB - Diadenosine tetraphosphate (AP4A) is an unusual nucleotide found in a variety of cells, including platelets. It has been suggested that platelet AP4A is stored in the dense granules and is metabolically inactive. We have studied the AP4A content of blood platelets in two patients and three cattle with Chediak-Higashi syndrome (CHS), a hereditary platelet defect with dense granule deficiency. Acid soluble extractions of whole blood and platelets were neutralized. The adenosine triphosphate (ATP) level was measured by luminescence technique. To measure the AP4A content, the neutralized extract was treated with phosphomonoesterase for removal of ATP. The AP4A content was then measured by coupling the phosphodiesterase and luciferase reaction. The AP4A content was 0.43 nmol/mg protein for normal human platelets and 0.004 nmol/mg protein for CHS platelets. The ATP/AP4A ratio was 67 for normal and 3,023 for CHS platelets. The whole blood AP4A was reduced by 89% in CHS patients who had only a slight decrease in ATP level (26% reduction). Similarly, bovine platelets with CHS showed a marked decrease of AP4A content and a moderate reduction of the ATP level. The platelet ATP/AP4A ratio was 351 and 3,133 for normal and CHS cattle, respectively. Results demonstrate a marked reduction of AP4A in CHS platelets and suggest that AP4A may be a useful marker for the measurement of dense granule content in platelets. PMID- 4027388 TI - In vitro megakaryocytopoiesis. PMID- 4027389 TI - Lectin agglutinability of the human hematopoietic stem cell. PMID- 4027390 TI - Progressive involution and physiological death of smooth muscle cells of rat incisal arterioles. AB - The sequential morphology of vascular smooth muscle cell involution and physiological cell death was studied by electron microscopy on rat incisors. Concurrently with changes in the pulp of the continuously growing incisor, its arterioles pass through a cycle of growth, remodeling, regression and decay. During the cycle, smooth muscle cells of the arterioles were observed to involute by segregation of cytoplasmic components, formation of autophagic and digestive vacuoles and shedding of cell fragments. Phagocytic vacuoles were found in neighbouring muscle cells and in adventitious macrophages. Concomitant with the involution in some cells, physiological death was observed among other smooth muscle cells. This appears as an apoptosis with sequential transformations of polyribosomes into monoribosomes, nuclear and cytoplasmic condensation, and finally fragmentation followed by phagocytosis mainly by adventitious macrophages. Knowledge of the features of physiological involution and cell death of the vascular smooth muscle cells may be of importance not only in studies of functional remodeling and adaption, but also in the interpretation of vascular lesions. PMID- 4027391 TI - Reactivity of small vessels from mature to senescent female rabbits. AB - In order to determine if there are differences in reactivity of small arteries of cutaneous and skeletal muscle vascular beds taken from rabbits of different ages, vascular smooth muscle strips were tested in vitro with a variety of drugs. Arteries from the ear and hind limb skeletal muscle were removed from adult female rabbits, aged 6-48 months. Developed force of the vessel strips was measured during exposure to cumulative concentrations of norepinephrine, norepinephrine following propranolol, angiotensin II (skeletal muscle artery only) and histamine (ear artery only). Comparable segments of arteries from rabbits of different ages showed no significant differences in size or in maximum developed force attributable to age. A lack of beta-adrenoceptor activity was indicated in the ear arteries of all adult age groups studied, while propranolol enhanced contractile responses to norepinephrine in skeletal muscle arteries independent of age. Likewise, there were no consistent, age-related changes in the reactivity of either vessel type to norepinephrine, histamine, or angiotensin. This study indicates that small cutaneous and skeletal muscle arteries from mature female rabbits do not undergo any appreciable change in adrenergic and nonadrenergic sensitivity with age. PMID- 4027392 TI - Altered catecholamine contents in vascular and nonvascular tissues in genetically hypertensive rats. AB - We have measured the catecholamine (CA) contents in hearts, mesenteric vasculature, abdominal aorta, inferior vena cava, vasa deferentia and salivary glands from genetically hypertensive rats (SHR) and normotensive Kyoto-Wistar rats (WKY). We noted differences between the norepinephrine (NE) contents of individual tissues from SHR and WKY rats and have used two different analytical procedures for the measurement of NE to confirm these differences. Comparisons between tissue contents of NE in SHR and WKY rats indicated a greater content of NE in the following tissues from the SHR: heart, mesenteric artery, abdominal aorta, inferior vena cava and vasa deferentia. A modest elevation of NE [but not epinephrine (E)] was observed in adrenal glands from SHR rats. The NE contents of salivary glands from SHR and WKY rats were indistinguishable from each other. The results suggest that there may exist a generalized increase in NE contents in the peripheral vasculature of SHR rats. Furthermore, this increase is also present in the vasa deferentia, but not the salivary gland. The results draw attention to altered concentrations of NE in vascular and selected nonvascular tissues in the SHR. PMID- 4027394 TI - Strategies to identify or prevent drug resistance in cancer. A panel discussion. PMID- 4027393 TI - Antiestrogen action in breast cancer cells: modulation of proliferation and protein synthesis, and interaction with estrogen receptors and additional antiestrogen binding sites. AB - Antiestrogens have proven to be effective in controlling the growth of hormone responsive breast cancers. At the concentrations of antiestrogens achieved in the blood of breast cancer patients taking antiestrogens (up to 2 X 10(-6) M), antiestrogens selectively inhibit the proliferation of estrogen receptor containing breast cancer cells, and this inhibition is reversible by estradiol. Antiestrogens also inhibit estrogen-stimulation of several specific protein synthetic activities in breast cancer cells, including increases in plasminogen activator activity, progesterone receptor levels and production of several secreted glycoproteins and intracellular proteins. Antiestrogens bind with high affinity to the estrogen receptor and to additional microsomal binding sites to which estrogens do not bind. These latter sites, called antiestrogen binding sites (AEBS), are present in equal concentrations in estrogen receptor-positive and -negative breast cancer cells and are present in a wide variety of tissues, with highest concentrations being found in the liver. The antiestrogenic and growth suppressive potencies of a variety of antiestrogens correlate best with their affinity for estrogen receptor and not with affinity for AEBS. Antiestrogens undergo bioactivation and metabolism in vivo and hydroxylated forms of the antiestrogen have markedly enhanced affinities for the estrogen receptor. Detailed studies with high affinity radiolabelled antiestrogens indicate that antiestrogens induce important conformational changes in receptor that are reflected in the enhanced maintenance of a 5 S form of the estrogen receptor complex; reduced interaction with DNA; and altered activation and dissociation kinetics of the antiestrogen-estrogen receptor complex. These conformational changes effected by antiestrogens likely result in different interactions with chromatin, causing altered cell proliferation and protein synthesis. Analyses of the rates of synthesis and turnover of the estrogen receptor through pulse-chase experiments utilizing the covalently attaching antiestrogen, tamoxifen aziridine, and studies employing dense amino acid labeling of estrogen receptor reveal that the antiestrogen-occupied receptor is degraded at a rate (t 1/2 = 4 h) similar to that of the control unoccupied receptor. Hence, antiestrogens do not prevent estrogen receptor synthesis and they do not either accelerate or block estrogen receptor degradation.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 4027395 TI - Tissue mast cells in breast cancer. AB - The total number of mast cells and the number of such cells observed within and at the periphery of invasive breast cancers from 424 patients enrolled in protocol 4 of the National Surgical Adjuvant Breast Project were correlated with 38 other pathologic and 6 clinical features. High total mast cell counts as well as those within and at the periphery of the cancers were found to be significantly (p less than or equal to .05) associated with a patient age less than 50 years and the degree of tumor lymphoid cell reaction. The latter has also been found to be related to young age and other pathologic characteristics related to mast cell content. This suggests that the mast cells may simply represent another cell type of this reactive change. No differences in 10 year disease-free survival were detected in patients without mast cells and those exhibiting varying numbers of such cells. This information indicates that identifiable mast cells do not represent a prognostic pathologic discriminant in patients with breast cancer. However, this does not unequivocally exclude a role of mast cell secretory products, since only intact and not degranulated or disrupted forms of these cells can be counted. PMID- 4027396 TI - Prognostic implication of estrogen receptor content in breast cancer. AB - The cytosolic estrogen receptor (ER) content of the primary tumor was determined by isoelectric focusing in 170 consecutive women with unilateral breast cancer diagnosed in 1977 through 1980. No adjuvant treatment over and above surgery and radiotherapy was given. The overall corrected survival was not significantly (p greater than 0.05) higher in ER-rich (less than 0.1 nmol/g DNA) than in ER-poor tumors, but the median period from recurrence to death was longer in the former (16 months) than in the latter (10 months) group. The difference in disease-free survival (DFS) in favour of the ER-rich tumors achieved its maximum-about 15% after two years (p less than 0.01). At prolonged follow-up, however, the curves converged and there was no significant difference when the whole six year period of observation was taken into account. In patients without axillary metastases the same pattern emerged, with earlier recurrences in ER-poor tumors and a difference in DFS between the two ER groups at two years (p less than 0.01) which was diminished after five years (p less than 0.05). The ER content provided no significant prognostic information in patients with axillary node metastases or locally advanced disease. We conclude from the present and other available data that the ER content in breast cancer would seem to be an indicator of growth rate rather than of metastatic potential and accordingly a predictor of the pattern of recurrence and length of disease-free survival rather than of long-term survival. PMID- 4027397 TI - Association of vaginal smear cytology with menstrual status in breast cancer. AB - The relationship of clinically defined menstrual categories and an independent measure of hormonal stimulation, maturation index of vaginal smear cytology, was studied. Analysis of 596 smears obtained at the time of breast cancer diagnosis revealed a statistically significant association between menstrual status and maturation index. However, within each menstrual group varying levels of maturation were noted. Estrogenic effect in the absence of exogenous hormone administration was found in 11% of patients following bilateral oophorectomy and among 24% of women whose natural menopause occurred 20 years or longer prior to diagnosis. Endogenous estrogen production appears to continue for many years among some women. Clinical factors such as obesity, diabetes and/or hypertension may stimulate high squamous maturation in some patients. Others of the same age and with similar clinical histories were found to have atrophic smears. The differences in maturation index may be due to individual variations in: endogenous hormone levels; sensitivity of the vaginal mucosa to similar hormonal stimuli; use of certain medications; or unidentified exogenous factors. The maturation index was found to be significantly associated with the following prognostic factors: weight relative to height, tumor size and estrogen receptor content of the primary tumor. These findings indicate that vaginal smear cytology may define specific subsets within menstrual categories which may be relevant to therapy and prognosis in breast cancer. PMID- 4027398 TI - Reversible cardiac arrhythmia in a breast cancer patient treated with recombinant alpha interferon. PMID- 4027399 TI - Lead concentrations in tissues of marsh birds: relationship of feeding habits and grit preference to spent shot ingestion. PMID- 4027400 TI - Nitrite exposure and respiration rates in fathead minnows. PMID- 4027401 TI - Responses of macrobenthos colonizing estuarine sediments contaminated with drilling mud containing diesel oil. PMID- 4027402 TI - Acute and chronic toxicity of technical picloram (4-amino-3,5,6 trichloropicolinic acid) to Daphnia magna Straus. PMID- 4027403 TI - Percent mortalities and LC50 values for selected microcrustaceans exposed to Treflan, Cutrine-plus, and MSMA herbicides. PMID- 4027404 TI - Effects of ammonia on selected hepatic microsomal enzyme activity in mice. PMID- 4027405 TI - Inhibition of liver glycolysis in rats by dietary dichlone (2,3-dichloro-1,4 naphthoquinone). PMID- 4027406 TI - Heavy metal concentrations in tissues of mink in Virginia. PMID- 4027407 TI - Heavy metal concentrations in municipal wastewater treatment plant sludge. PMID- 4027409 TI - Residues of cypermethrin in milk from cows wearing impregnated ear tags. PMID- 4027410 TI - Organochlorine residue levels in human milk from Baghdad. PMID- 4027408 TI - Removal of GC background interferences from reagents used in fumigant analysis. PMID- 4027411 TI - Sweat-patch test for monitoring pesticide absorption by airblast applicators. PMID- 4027412 TI - Factors influencing the high content of brominated trihalomethanes in Barcelona's water supply (Spain). PMID- 4027413 TI - Separating starvation losses from other early feeding fry mortality in steelhead trout Salmo gairdneri, chinook salmon Oncorhynchus tshawytscha, and lake trout Salvelinus namaycush. PMID- 4027414 TI - Thermoregulation in a naturally oil-contaminated black-billed murre Uria aalge. PMID- 4027415 TI - Molt-inhibition in the crab Oziotelphusa senex senex following exposure to malathion and methyl parathion. PMID- 4027416 TI - Effects of monomethylhydrazine on selected species of marine diatoms. PMID- 4027417 TI - Purification and characterization of lead-induced zinc thionein in the liver of rats. PMID- 4027418 TI - Influence of dietary aflatoxin, zinc, and copper on bone size, organ weight, and body weight in hamsters and rats. PMID- 4027419 TI - Accumulation of methylmercury in the earthworm, Eisenia foetida, and its effect on regeneration. PMID- 4027420 TI - Heavy metal concentrations of duck tissues in relation to ingestion of spent shot. PMID- 4027421 TI - Changes in eggshell thickness during incubation: implications for evaluating the impact of organochlorine contaminants on productivity. PMID- 4027422 TI - Tissue distribution of trace elements and DDE in brown pelicans. PMID- 4027423 TI - Use of tree bark to monitor radionuclide pollution. PMID- 4027424 TI - House treatment with organochlorine pesticides and their levels in human milk- Perth, Western Australia. PMID- 4027425 TI - Dislodgeable residues of carbophenothion in Florida citrus: implications for safe worker reentry. PMID- 4027426 TI - Preliminary evaluation of the use of macrophage aggregates (MA) as fish health monitors. PMID- 4027427 TI - Renal pathology in fish (Puntius conchonius Ham.) following exposure to acutely lethal and sublethal concentrations of monocrotophos. PMID- 4027428 TI - Effect of aniline on Chlorella vulgaris. PMID- 4027429 TI - Genotoxic activity of particulate material in petroleum refinery effluents. PMID- 4027430 TI - Application of acute bioassays in evaluating the treatment of coal liquefaction wastewaters. PMID- 4027431 TI - Multivariate analysis of water contamination by heavy metals at Donana National Park. PMID- 4027432 TI - Brominated phenols and anisoles in river and marine sediments in Japan. PMID- 4027434 TI - The lung in growth and ageing. 19th annual congress of the European Society for Clinical Respiratory Physiology (SEPCR). The Hague, 24-28 June 1985. Abstracts. PMID- 4027433 TI - Movement of bromacil and norflurazon in a sandy soil in Florida. PMID- 4027435 TI - Study of age dependent half-life of iodine in man: a reinforcement-depletion urn model. PMID- 4027436 TI - Polynucleotide evolution and branching processes. PMID- 4027437 TI - Fractals and the analysis of growth paths. PMID- 4027438 TI - Depolarized potassium currents and time delay in nerve membrane. PMID- 4027439 TI - Practical aspects of the instrumental management of tinnitus. PMID- 4027440 TI - The Crown-Crisp Experiential Index in patients complaining of tinnitus. AB - The Crown-Crisp Experiential Index (CCEI) was administered to 472 patients complaining of tinnitus who took part in a multi-centre study on tinnitus masking (Hazell et al., 1985). This inventory includes scales of anxiety, phobic anxiety, obsessionality, somatic anxiety, depression and hysteria. The scores on the CCEI scales for patients with and without 'dizziness' as an additional symptom were compared. In the non-dizzy patients, scores on the anxiety and depression scales were consistently elevated compared with the published normative values. In the dizzy patients scores on all scales except Hysteria were elevated. The most pronounced and consistent difference between the dizzy and non-dizzy patients was in the Somatic Anxiety scale. The presence of dizziness also obscured the relationship between the CCEI scales and measures of tinnitus. In contrast, however, hearing disability did not appear to influence the results. PMID- 4027441 TI - Health care machine-readable data files: secondary analysis, access, and the role of the library. AB - Access to health care machine-readable data files (MRDF) is becoming increasingly important to students and researchers in the health care field who use the data in secondary analysis. Health sciences libraries must play a role in providing such access, and this role should consist primarily in providing users with information about the identity and contents of available MRDF and about how they may be obtained. Libraries should therefore collect extensive materials containing information about the MRDF that may be of interest to their users. Many such materials are available in print, and their quality may be expected to improve as newly developed methods and procedures for constructing bibliographic citations, abstracts, and catalog entries for MRDF are put into practice. Also, it is now feasible to incorporate data file abstracts into existing online bibliographic databases. PMID- 4027442 TI - Bibliographic research and critical inquiry: a learning module for graduate students in health services administration. AB - Critical to the success of contemporary health administration practice is the ability to identify, access, synthesize, apply, and report information from a diversity of sources. To enhance the critical logic and bibliographic research skills of first-semester graduate students in health services administration, a fifteen-hour learning module was collaboratively developed and integrated into a required course on health care organization. Reference librarians and health administration faculty participate to provide both group and individual instruction. PMID- 4027443 TI - Program planning for the community teaching hospital medical library. AB - To respond to the increasing demand for information from medical educators and clinicians and to persuade administrators to purchase the newly available microcomputer library systems, medical librarians in community teaching hospitals may find it useful to engage in intermediate term (for example, five-year) program planning. To increase the probability that the plan which emerges will be implemented, the planning process should fit the organizational nexus. Planning involves needs assessment, prioritized program elements, a written plan, and facilities planning (if applicable), which lead to program implementation. Components of a model program plan are presented. PMID- 4027444 TI - Getting started with electronic mail. AB - This paper gives suggestions to librarians on how to get started with electronic mail. It discusses the cost- and time-saving advantages of using electronic mail rather than TWX, United States mail, or telephones for communicating ILL requests and messages. For instance, preliminary cost data show that electronic mail is often half as expensive as TWX and costs no more than a 22 stamp. Key management concerns that must be considered when setting up electronic mail are discussed, including the need for subscribers to agree on one system. Also covered are the types of equipment that can be used with electronic mail, including print terminals. PMID- 4027445 TI - Implementing change: the installation of an integrated library system at UTHSCSA. AB - The implementation of the Library Information System (LIS) and the distributed PHILSOM system at the University of Texas Health Science Center at San Antonio Library is described. These systems were installed over a ten-month period in 1982-1983. Aspects of the implementation, including equipment, staffing, scheduling, data preparation, and public relations, are reviewed. Evaluation of LIS and its costs are discussed. PMID- 4027446 TI - A cooperative medical library/public library book sale: new avenue for marketing the academic health sciences library. PMID- 4027447 TI - British-U.S. job exchange. PMID- 4027448 TI - Differences between pastoral counseling and psychotherapy. PMID- 4027450 TI - New schistosomiasis control strategy endorsed. PMID- 4027449 TI - Availability and utilization of new medical technology in Mexico: results of a national study. PMID- 4027451 TI - Long-term storage of IgG and IgM on filter paper for use in parasitic disease seroepidemiology surveys. PMID- 4027452 TI - The seasonality of infant deaths due to diarrheal and respiratory diseases in southern Brazil, 1974-1978. PMID- 4027453 TI - Mixed rehydration. PMID- 4027454 TI - Perinatal care in six eastern Caribbean countries. PMID- 4027455 TI - Evaluation of chlorphoxim used against Anopheles albimanus on the south coast of Mexico: 2. Use of two curtain-trap techniques in a village-scale evaluation trial. PMID- 4027456 TI - Acute respiratory infections in children: possible control measures. PMID- 4027457 TI - Health services research in the Americas. PMID- 4027458 TI - Disaster assessment: the weak link in international relief efforts. PMID- 4027459 TI - WHO and UNICEF recommend new oral rehydration salts (ORS) formulation. PMID- 4027461 TI - Inhibition of tolbutamide metabolism by substituted imidazole drugs in vivo: evidence for a structure-activity relationship. AB - Tolbutamide has been used as a model drug for an examination of the effects of eleven substituted imidazole compounds on hepatic metabolism in vivo. The 1 substituted compounds 1-methylimidazole, miconazole, clotrimazole and ketoconazole produced marked alterations in tolbutamide kinetics (increased half life, decreased clearance). However, if there was substitution in the 2- position, irrespective of a substituent on N-1, then the compound did not appear to inhibit metabolism (e.g. 2-methylimidazole, 1,2-dimethylimidazole, methimazole, metronidazole). The 4- substituted compounds, 4-methylimidazole and cimetidine were inhibitors. A structure-activity relationship for the inhibitory actions of the substituted imidazoles is thus evident in vivo. PMID- 4027460 TI - Effects on rabbit cardiac potentials of aprindine and indecainide, a new antiarrhythmic agent, in normoxia and hypoxia. AB - Intracellular potentials were recorded from rabbit atria, cardiac Purkinje cells and papillary muscles before and after exposure to various concentrations of indecainide. The effects of aprindine also were studied in the atrial preparations. Both drugs depressed the maximum rate of depolarization (MRD) in a dose-related manner, indecainide being approximately ten times more potent than aprindine. Aprindine caused a dose-related bradycardia, but indecainide had no significant effect on sinus node frequency. Indecainide had a dose-related negatively inotropic effect in normal, half-normal and twice-normal extracellular calcium concentrations. Indecainide shortened action potential duration (APD) in atrium and Purkinje cells but prolonged APD to 50% repolarization in ventricular muscle. The actions of indecainide were extremely persistent. No significant recovery of MRD was observed after pauses in stimulation of up to 16 s. Indecainide had no effect on effective refractory period (ERP) measured by interpolated premature stimuli. Indecainide is therefore categorized as a Class 1c antiarrhythmic agent. The effects of both aprindine and indecainide on MRD were increased in hypoxic atria. Conduction velocity in hypoxic atria exposed to indecainide was greater than in controls, however, suggesting the possibility of improved cell-to-cell coupling. PMID- 4027462 TI - Mechanisms underlying electrical and mechanical responses of the bovine retractor penis to inhibitory nerve stimulation and to an inhibitory extract. AB - The response of the bovine retractor penis (BRP) to stimulation of non adrenergic, non-cholinergic (NANC) inhibitory nerves and to an inhibitory extract prepared from this muscle have been studied using intracellular microelectrode, sucrose gap and conventional mechanical recording techniques. Both inhibitory nerve stimulation and inhibitory extract hyperpolarized the membrane potential and relaxed spontaneous or guanethidine (3 X 10(-5) M)-induced tone. These effects were accompanied by an increase in membrane resistance. Following membrane potential displacement from an average value of -53 +/- 7 mV (n = 184; Byrne & Muir, 1984) inhibitory potentials to nerve stimulation were abolished at approximately -30 mV; there was no evidence of reversal. Displacement by inward hyperpolarizing current over the range -45 to -60 mV increased the inhibitory response to nerve stimulation and to inhibitory extract; at more negative potential values (above approximately -60 mV) the inhibitory potential decreased and was abolished (approximately -103 mV). There was no evidence of reversal. Removal of [K+]o reversibly reduced hyperpolarization to nerve stimulation and inhibitory extract. No enhancement was observed. Increasing the [K+]o to 20 mM reduced the inhibitory potential to nerve stimulation but this was restored by passive membrane hyperpolarization. Inhibitory potentials were obtained at membrane potential values exceeding that of the estimated EK (-49 mV). [Cl-]o free or [Cl-]o-deficient solutions reduced and abolished (after some 20-25 min) the hyperpolarization produced by inhibitory nerve stimulation or inhibitory extract. The inhibitory potential amplitude following nerve stimulation was not restored by passive displacement of the membrane potential from -26 to -104 mV approximately. Ouabain (1-5 X 10(-5) M) reduced then (45-60 min later) abolished the inhibitory potential to nerve stimulation. The effects of this drug on the extract were not investigated. It is concluded that the inhibitory response to nerve stimulation and extract in the BRP may involve several ionic species. However, unlike that in gastrointestinal muscles the NANC response in the BRP is accompanied by an increased membrane resistance and does not primarily involve K+. The underlying mechanisms for the inhibitory response to both NANC nerve stimulation and inhibitory extract appear to be similar, compatible with the view that the latter may contain the inhibitory transmitter released from these nerves in this tissue. PMID- 4027463 TI - Effects of caffeine on hippocampal pyramidal cells in vitro. AB - The effects of caffeine on the electrophysiological properties of CA1 pyramidal neurones were investigated in the rat hippocampal slice preparation in vitro. A concentration-dependent increase in both the extracellularly recorded excitatory postsynaptic potential (e.p.s.p.) and the population spike resulting from stimulation of the stratum radiatum could be evoked by caffeine with a threshold concentration of 10 microM. Intracellular recordings demonstrate a caffeine evoked decrease in resting membrane potential, an increase in input resistance, a reduction of the long afterhyperpolarization (a.h.p.) and a decrease in accommodation. The interaction between caffeine and adenosine was investigated on the extracellularly recorded e.p.s.p. The maximal response evoked by caffeine was increased in the presence of adenosine and the adenosine concentration-response curve was shifted to the right in a parallel fashion in the presence of caffeine. It is suggested that the effects of caffeine on hippocampal neurones may be mediated by a decrease of one or more potassium conductance(s), and that adenosine and caffeine may compete for the same electrophysiologically active receptor site on these cells. PMID- 4027464 TI - Ketamine-inhibition of calcium-induced contractions in depolarized rat uterus: a comparison with other calcium antagonists. AB - The inhibitory effect of the intravenous anaesthetic ketamine on CaCl2-induced contractions in the isolated K+-depolarized uterus of the rat in Ca2+-free medium was compared with that produced by papaverine, theophylline and the calcium entry blocker verapamil. Pre-incubation for 20 min with either ketamine (0.3 to 3 mM), papaverine (3 to 30 microM), theophylline (0.1 to 1 mM) or verapamil (3 to 30 nM) induced parallel, concentration-dependent rightward displacements of the dose response curves to Ca2+ (0.04 to 22 mM). The antagonism was competitive, except that due to verapamil, the Schild plot for which yielded a slope which differed significantly from unity. The calculated pA2 values (+/- s.e.mean) were: ketamine 3.90 +/- 0.07; papaverine 5.55 +/- 0.05; theophylline 3.99 +/- 0.1 and verapamil 9.54 +/- 0.24. These drugs differed in their ability to relax the sustained contraction induced by Ca2+ (1 mM) in K+-depolarizing solution. Ketamine and verapamil relaxed the preparation in a concentration-dependent manner whereas theophylline and especially papaverine were less potent and induced only partial maximal relaxation. The t1/2 of the relaxant effect was significantly less for ketamine than for verapamil (5 and 22 min, respectively). Only ketamine produced a relaxation comparable to that obtained by washing the preparation with Ca2+ free solution (t1/2 = approx. 5 min). Prior exposure of the depolarized uterine strip to a low concentration of Ca2+ (0.22 mM) increased the potency of ketamine, but decreased that of papaverine and theophylline, in antagonizing Ca2+ induced contractions. In contrast, this procedure did not affect the potency of verapamil. 5 The inhibitory effects of these drugs, excluding those of verapamil, were completely reversed after washing the preparations with a high-potassium Ca2+-free solution, 3-5 times for about 30-60 min. 6 These experiments provide further evidence that the relaxant effect produced by ketamine on the rat isolated uterus is due to its ability to antagonize Ca2+ movements competitively and also show that there are marked differences between the nature of the relaxant effects of ketamine and those of papaverine, theophylline and verapamil. PMID- 4027465 TI - Age-related changes in the sensitivity to verapamil and sodium nitroprusside of vascular smooth muscle of rabbit aorta. AB - Age-related changes in the sensitivity to verapamil and sodium nitroprusside were examined in isolated aortic strips of the rabbit. In the aortae of newborn rabbits within 10 days of birth, the resting tone of the muscle was strongly reduced by sodium nitroprusside but not by either Ca-deficient solution or by verapamil. High K-induced contraction and noradrenaline-induced contraction were both inhibited by verapamil or sodium nitroprusside. In the aortae of 24 day-old rabbits, resting tension was slightly reduced by sodium nitroprusside but not by verapamil. High K-induced contraction was less sensitive to sodium nitroprusside than to verapamil whereas noradrenaline-induced contraction was less sensitive to verapamil than to sodium nitroprusside. In the aortae isolated from 60 day-old or older rabbits, resting tension was not affected by either sodium nitroprusside or verapamil. High K-induced contraction was inhibited by verapamil whereas sodium nitroprusside showed only a weak inhibitory effect. Noradrenaline-induced contraction was inhibited by sodium nitroprusside although verapamil had only a slight inhibitory effect. In the aortae of 1 day-old and also in adult rabbits, noradrenaline induced an additional increase in muscle tension when applied during the sustained contraction induced by high K. It is suggested that, in the newborn rabbit aorta, the voltage-dependent Ca channel is sensitive to both verapamil and sodium nitroprusside and the sensitivity to sodium nitroprusside gradually decreases during maturation whereas the receptor-linked Ca channel is also sensitive to both of the inhibitors at birth but the sensitivity to verapamil gradually decreases with age. PMID- 4027466 TI - Effects of pentobarbitone on acetylcholine-activated channels in mammalian muscle. AB - Acetylcholine-activated single channel currents were recorded from the extrajunctional region of chronically denervated skeletal muscle of the rat by the patch clamp technique. In control experiments, the cumulative open-time, closed-time and burst length distributions could be well described by the sum of two exponentials. Pentobarbitone decreased the mean open time and increased the time constant of the fast component of the closed time distribution. These effects increased with drug concentration. The mean burst length was relatively independent of pentobarbitone concentration over the range of concentrations used (10-500 microM). These observations are inconsistent with a simple sequential blocking model and it is suggested that pentobarbitone has an allosteric site of action on receptor-channel complexes that makes the open state less stable. PMID- 4027467 TI - Comparison of the antagonistic effects of phentolamine on vasoconstrictor responses to exogenous and neurally released noradrenaline in vivo. AB - The antagonistic effects of the alpha-adrenoceptor blocking agent phentolamine on vasoconstrictor responses to intraluminal noradrenaline and lumbar sympathetic nerve stimulation were compared in the hindlimb of the anaesthetized dog. Sympathetic stimulation with 1 pulse or trains of 4-10 pulses at 0.4-40 Hz produced graded vasoconstrictor responses that were matched in amplitude by intra arterial injections of 10(-8) - 10(-6) g noradrenaline. Phentolamine (0.5 mg kg-1 i.v.) attenuated amplitude-matched responses to both types of stimuli to quite similar extents. The extent of the effect of phentolamine on neurogenic responses was greater with 1 pulse stimulation than with trains, and greater with 4 pulse than with 10 pulse trains. The effect was maximal within 2 min of phentolamine administration and wore off in parallel with that on responses to injected noradrenaline. The results are consistent with the view that transmitter released from noradrenergic vasoconstrictor nerves acts primarily on subjunctional alpha adrenoceptors. PMID- 4027468 TI - A comparison of several calcium antagonists on uterine, vascular and cardiac muscles from the rat. AB - An assessment was made of the potencies of nifedipine, gallopamil, diltiazem, cinnarizine and salbutamol as inhibitors of tension development by the uterus and cardiovascular tissues from the term pregnant rat. The rank order of potency was nifedipine greater than gallopamil greater than diltiazem for those preparations on which these compounds were potent, viz. spontaneous and oxytocin-induced tension development of the uterus, spontaneous tension development of hepatic portal vein, potassium chloride (KCl)-induced pressure rises of perfused mesenteric bed and electrically-stimulated (0.5 Hz) ventricular muscle. The rank order of potency of nifedipine, gallopamil and diltiazem was different for those preparations on which they exhibited low potency, viz. noradrenaline-induced pressure rises of perfused mesenteric bed and tension development of aorta. Gallopamil and diltiazem, but not nifedipine, were more potent against tension development by ventricular muscle stimulated at 2.5 Hz than at 0.5 Hz, suggesting that nifedipine interacts at a different site from the other compounds. Cinnarizine was less potent than the other calcium antagonists on the uterus and portal vein, was the second most potent compound against KCl-induced pressure rises of the mesenteric bed and was equipotent against responses to noradrenaline and KCl of the mesenteric bed (unlike the other compounds). This suggests that the site of action of cinnarizine differs from that of the other calcium antagonists. Nifedipine, gallopamil and diltiazem, like salbutamol, exhibited selectivity for inhibition of tension development by the uterus relative to the cardiovascular tissues. PMID- 4027469 TI - The potencies and selectivities of four calcium antagonists as inhibitors of uterine contractions in the rat in vivo. AB - The potencies of four calcium antagonists (nifedipine, gallopamil, verapamil and diltiazem) at inhibiting uterine contractions in vivo have been assessed in the conscious ovariectomized, post-partum rat. Their selectivities for this action, relative to their effects on blood pressure and heart rate, have been compared with salbutamol. All compounds produced a dose-dependent inhibition of intra uterine pressure cycles. The rank order of potency was salbutamol greater than nifedipine greater than diltiazem = gallopamil greater than verapamil. All compounds produced a dose-dependent fall of mean blood pressure. The rank order of potency was salbutamol greater than nifedipine greater than gallopamil greater than verapamil greater than diltiazem. Salbutamol and nifedipine produced a tachycardia, which was very marked with salbutamol. Gallopamil, verapamil and diltiazem induced a moderate tachycardia at low doses but temporary cessation of heart beat occurred at high doses. Nifedipine and diltiazem, like salbutamol, exhibited some selectivity for inhibition of uterine contractions relative to their cardiovascular actions. Gallopamil and verapamil showed no selectivity for the uterus. PMID- 4027470 TI - Quantification of the characteristics of antagonists exhibiting both competitive antagonism and functional interaction. AB - Null equations have been derived which, when applied to log10 concentration tissue state curves for an agonist determined in the presence and absence of a competitive antagonist which also exhibits functional interaction, allow quantitation of the characteristics of the competitive and functional interactant effects. Both the affinity constant of the antagonist for its receptors and numerical values characterizing the functional interaction can be obtained. The null equations have been tested in a model system by using a mixture of papaverine hydrochloride (either 5 or 20 microM) and methyl atropine bromide (10 nM) to mimic a competitive antagonist which also shows functional interaction. Agreement between values derived directly and indirectly from the model is good and validates the use of the null equations. PMID- 4027471 TI - Effect of exposure to radiation on the inflammatory process and its influence by diclofenac. AB - The effect of radiation exposure on the inflammatory process was studied in rats using the carrageenan-induced paw oedema and adjuvant-induced arthritis tests. Irradiation (0.5,1 and 2 Grays) resulted in a significant augmentation of the tissue response to carrageenan and the early phase of adjuvant-induced arthritis, but suppressed the late phase. Diclofenac (1-5 mg kg-1) effectively reduced the exaggerated inflammatory response in irradiated animals in both the carrageenan paw oedema and adjuvant-induced arthritis tests. The drug also had a prophylactic value in guarding against the induction of radiation damage. The inflammatory responses produced by irradiation and the benefits obtained by drug treatment may be related to changes in tissue prostaglandin levels and/or changes in the immune system. PMID- 4027473 TI - Histamine is an antagonist of the acetylcholine receptor at the frog endplate. AB - The effects of histamine on the acetylcholine (ACh) receptor-channel complex were examined by means of voltage-clamp at the frog endplate. ACh was ionophoretically applied to the endplate. Histamine was added to the perfusate. Histamine (100 nM 1 mM) reversibly depressed the peak amplitude of the ACh-induced inward current in a dose-dependent manner. The double reciprocal plot of the dose-response relationship between the peak ACh current and the amount of ACh applied suggested that histamine (100 microM) depressed the ACh-induced current in a competitive manner. Histamine prevented the specific ACh binding site within the receptor channel complex from binding erabutoxin, a sea-snake venom, which binds irreversibly to the specific ACh binding site. Histamine had no detectable effects on the equilibrium potential of the endplate current but shortened the half-decay time of the endplate current in a voltage-dependent manner. It was therefore concluded that histamine blocks not only the specific ACh binding site but also interacts with the ACh-channel site. The present experiments strongly suggest that histamine can act as an antagonist to modulate nicotinic cholinergic transmission. PMID- 4027474 TI - Modification of vasopressin- and angiotensin II- induced changes by calcium antagonists in the peripheral circulation of anaesthetized rabbits. AB - Investigations into the site of vasodilator and antivasoconstrictor activity of calcium antagonists previously performed in cats were extended to a second species, barbiturate-anaesthetized rabbits, and a second vasoconstrictor agent, vasopressin. The dihydropyridine derivative darodipine (code name PY 108-068; 10, 30 and 100 micrograms kg-1 i.v.) showed systemic haemodynamic effects comparable to those seen in cats at half these doses. Darodipine effected regional vasodilatation (measured with tracer microspheres) in the heart, brain and skeletal muscles as in cats. Only the vessels of the adrenals (dilated in rabbits but not in cats), and the kidneys and skin (constricted in rabbits but not in cats) responded differently to darodipine. Angiotensin II (A II; 0.15 and 1.5 micrograms kg-1 min-1) constricted the same vascular beds in rabbits as in cats, namely the heart, kidneys, small intestine, pancreas, spleen, skin and arterio venous shunts (inferred from microspheres reaching the lungs), the only exceptions being the vessels of the stomach and liver (constriction only in cats) and the adrenals (constriction only in rabbits). Darodipine (30 and 100 micrograms kg-1) attenuated the A II-induced vasoconstriction in the same vascular beds in rabbits as in cats including the kidneys, which were constricted after administration of the antagonist alone. These results indicate surprisingly small species differences for the vasodilator effects of darodipine as well as the attenuation of the vasoconstrictor effects of A II. Lysine-vasopressin (2 and 50 mu kg-1 min-1) did not increase blood pressure in anaesthetized rabbits but dose-dependently lowered heart rate, cardiac output, total peripheral conductance and myocardial contractile force (measured with a strain gauge). Vasopressin constricted all peripheral vascular beds dose-dependently, except for those of the kidney and liver. The effects of vasopressin persisted in the animals infused with placebo solution. Darodipine (30 and 100 micrograms kg-1), but not verapamil (300 and 1000 micrograms kg-1) reversed the vasopressin-induced cardiac depression and decrease in cardiac output. This probably also explains most of the apparent differences between the effects of the two calcium antagonists on the peripheral circulation. Both calcium antagonists diminished the vasopressin constriction in most vascular beds except those of the spleen, skin and arterio venous shunts. Most of the effects were dose-related but not strictly competitive, as far as this can be judged based on two doses of agonist and antagonist. 9 As with A II the effects of vasopressin were diminished in vascular beds not normally dilated by calcium antagonists. 10 Calcium antagonists display two typical patterns of activity. The vasodilator pattern consists of dilatation of the vesels of the heart, brain and, to a degree varying with the agents, skeletal muscle. The antivasoconstrictor effects occur in some but not all of the vessels constricted by the constrictor agent, vasoconstriction of the spleen, skin and arterio-venous shunts being resistant to the action of calcium antagonists. The pattern of antivasoconstrictor activity appears to depend on the constrictor compound used, inasmuch as such agents constrict different vascular beds. PMID- 4027472 TI - Comparison of negative inotropic potency, reversibility, and effects on calcium influx of six calcium channel antagonists in cultured myocardial cells. AB - The negative inotropic effects of calcium channel antagonists on the myocardium were used as a standard for the definition and determination of potency of this group of drugs. The effects of six calcium channel antagonists (verapamil, methoxyverapamil (D600), nifedipine, lidoflazine, perhexiline and diltiazem) were compared on cultured chick embryo ventricular cells. Drug concentrations producing 50% inhibition of contractile amplitude, derived from linearized concentration-response curves, varied from 2.8 X 10(-8)M for nifedipine to 8.3 X 10(-7)M for perhexiline. Equipotent negative inotropic concentrations of verapamil, D600, perhexiline, diltiazem and lidoflazine produced a similar inhibitory effect on 45Ca uptake into cultured cells. Nifedipine produced no significant inhibition of 45Ca uptake. The time required for recovery of contractility after cessation of drug superfusion varied in the order lidoflazine greater than perhexiline greater than D600 greater than verapamil greater than nifedipine greater than diltiazem. This relative order accords closely with the reported in vivo half-lives of these drugs. It is concluded that while some inhibition of 45Ca2+ uptake into cardiac cells can be demonstrated with five of the six calcium channel blockers studied, the relationship between the degree of inhibition of calcium influx and negative inotropic effects may not be uniform for all calcium channel antagonists. PMID- 4027475 TI - Effect of verapamil and diltiazem on calcium-dependent electrical activity in cardiac Purkinje fibres. AB - The effects of verapamil and diltiazem on normal action potentials, abnormal automaticity at depolarized membrane potential and oscillatory afterpotentials were compared in sheep cardiac Purkinje fibres. Concentrations of verapamil and diltiazem exerting the same action on abnormal automaticity due to slow action potentials, caused different effects on action potential characteristics and on oscillatory afterpotentials. Diltiazem significantly shortened action potential duration whereas verapamil slightly lengthened it (NS). Diltiazem appeared to be more effective than verapamil in preventing the development of oscillatory afterpotentials induced by barium or by strophanthidin. In 50% of barium-treated preparations, verapamil caused the appearance of spontaneous activity due to enhanced normal diastolic depolarization, while diltiazem had no such effect. The observed differences were explained in terms of the different effects of the two drugs on currents other than the slow inward current, since diltiazem was more potent than verapamil in depressing Vmax. PMID- 4027476 TI - Regional variation in the sensitivity of longitudinal smooth muscle to histamine at H1-receptors in guinea-pig ileum and colon. AB - The sensitivity of the distal ileum, proximal colon, medial colon, and distal colon of the guinea-pig to histamine has been evaluated. The rank order of sensitivity was ileum greater than medial colon greater than proximal colon approximately equal to distal colon. The mean -logEC50 values at receptors in the ileum, medial, proximal, and distal colon were 6.74, 6.18, 5.79, and 5.72, respectively. The apparent dissociation constant for the interaction of histamine with receptors in the various regions was determined. The -log Kd values at receptors in the ileum, proximal colon, medial colon, and distal colon were 4.68, 4.65, 4.62, and 4.44, respectively. The mean apparent -log Kd values for the antagonism of histamine by mepyramine were 9.0, 9.0, 9.1, and 8.9 for receptors on the ileum, proximal, medial, and distal colon, respectively. The results of these experiments provide no evidence that histamine receptors in the colon are distinguishable from H1-receptors as characterized on the ileum. The differences in sensitivity to histamine in the various regions of the intestine may be due to differences in the density of H1-receptors. PMID- 4027477 TI - The effect of diltiazem on noradrenaline release. AB - The effects of diltiazem in rat tail arteries and guinea-pig vasa deferentia have been investigated. Superfusion of the rat tail artery with diltiazem (10(-6) - 10(-4) M) resulted in a dose-related increase in 3H-overflow (P less than 0.001) both in Wistar Kyoto (WKY) and in spontaneously hypertensive (SHR) rats. Release of 3H by transmural stimulation (1 Hz, 2 ms, 10 V) was also much greater in vessels perfused with diltiazem; this effect was dose-dependent. Diltiazem did not significantly alter the proportion of noradrenaline and its metabolites in 3H overflow, as analysed by column chromatography. In the vasa deferentia of guinea pigs, diltiazem (10(-9) - 10(-5) M) increased spontaneous 3H-release. The results indicate that diltiazem acts on sympathetic nerves and causes the release of noradrenaline. PMID- 4027478 TI - The mechanism of adenosine release from hypoxic rat liver cells. AB - Uptake of [14C]-adenosine into freshly dispersed rat hepatocytes was inhibited 44% by dipyridamole (50 microM) and 60% by nitrobenzylthioinosine (NBTI, 20 microM). The results are consistent with the known ability of these drugs to inhibit adenosine transport in other cell types. The nucleotide analogue, alpha, beta-methylene adenosine diphosphate (AOPCP, 50 microM), inhibited by 84% the degradation of exogenous 5' AMP that occurred rapidly when this substrate alone was presented to isolated hepatocytes. This confirms the ecto-5'-nucleotidase inhibitory properties of this analogue in isolated hepatocytes. During hypoxic incubation, isolated hepatocytes released adenosine, which accumulated in the extracellular volume. Dipyridamole and NBTI each markedly attenuated this extracellular adenosine accumulation. In contrast, AOPCP had no inhibitory effect on net hypoxic adenosine release. It is concluded that hypoxic rat hepatocytes produce adenosine intracellularly and that this adenosine is released via facilitated diffusion to the extracellular space, based on the inhibition observed with the transport inhibitors. The plasma membrane enzyme ecto-5' nucleotidase does not appear to participate in hypoxic adenosine release from these cells as indicated by the lack of effect of the nucleotidase inhibitor, AOPCP. PMID- 4027480 TI - No inotropic action of enkephalins or enkephalin derivatives on electrically stimulated atria isolated from lean and obese rats. AB - Inotropic actions of the endogenous enkephalins, leucine enkephalin [( Leu] enkephalin) and methionine enkephalin [( Met] enkephalin), and derivatives, [D Ala2-methionine] enkephalinamide (DAMEA) and [D Ala2-leucine]enkephalinamide (DALEA) were tested, alone or in combination with noradrenaline (NA), (+/-) isoprenaline or carbachol, on electrically-stimulated atria excised from Sprague Dawley, fatty, Zucker (fa/fa) and lean, hooded heterozygous (Fa/fa) rats. [Met] enkephalin, [Leu] enkephalin, DAMEA and DALEA (4 X 10(-7)M to 4 X 10(-4)M) caused no significant changes in atrial tension in any group compared to pre-injection control values or those following the infusion of Krebs-Henseleit control solution. NA and isoprenaline (10(-7) to 10(-6)M) caused significant, dose related increases in atrial tension in each of the three strains of rats tested with the Fa/fa group showing the greatest change and fastest rate of tension development. [Met] enkephalin, [Leu] enkephalin, DAMEA or DALEA (4 X 10(-6)M) infused concurrently with NA or isoprenaline (10(-6)M) evoked atrial tension changes within each group that were not different from those observed when NA or isoprenaline was administered alone. Carbachol (10(-9) and 10(-8)M) caused a dose related decrease (10% and 30-40%, respectively, from pre-injection control values) in atrial tension in auricles excised from all three groups. Again, infusion of [Met] enkephalin, [Leu] enkephalin, DAMEA or DALEA (4 X 10(-6)M) together with carbachol (10(-8)M) did not affect atrial tension changes of auricles isolated from any group compared to when carbachol was given alone. The results indicate that the endogenous pentapeptides, [( Met] or [Leu] enkephalin), or derivatives (DAMEA and DALEA) do not affect atrial tension of electrically stimulated auricles isolated from Sprague-Dawley, fa/fa or Fa/fa rats. In addition, these pentapeptides do not modify the positive inotropic actions of NA or isoprenaline or the negative inotropic effects of carbachol. It is suggested that in vivo, the enkephalins or enkephalin derivatives do not have a direct action on the heart to alter myocardial contractility. PMID- 4027479 TI - Mode of stimulatory actions of cadmium ion on the mouse diaphragm. AB - Effects of Cd2+ on the phrenic nerve-diaphragm preparation of the mouse varied markedly in media containing various Ca2+ concentrations. In normal 2.5 mM Ca2+ medium, Cd2+ inhibited acetylcholine release from nerve endings without appreciable effect on the muscle membrane. However, Cd2+ elicited stimulatory effects on the muscle membrane in low Ca2+ medium (10(-3)-1 mM). These stimulatory effects included the induction of spontaneous contractions, augmentation of twitch responses to direct electrical stimulation and potentiation of the muscle contracture induced by acetylcholine, carbachol and high K+. By contrast, caffeine contracture was not affected by Cd2+. Tetrodotoxin, procaine, cysteine and glycerol pretreatment abolished these stimulatory effects of Cd2+. Moreover, changing the ionic composition of the bathing medium to one containing low Na+, high K+, high Mg2+ or high Ca2+ also antagonized these effects of Cd2+. In contrast, low Mg2+ markedly potentiated the frequency of spontaneous contractions induced by Cd2+. (+)-Tubocurarine and beta bungarotoxin had no effect on Cd2+-induced spontaneous contractions indicating that they may be myogenic rather than neurogenic in origin. By use of conventional microelectrodes, it was found that Cd2+ not only depolarized the muscle membrane but also induced spontaneous action potentials at a high frequency (173 +/- 17 Hz). It is concluded that increased Na+ permeability of the muscle membrane is the essential step bringing about spontaneous contractions. The binding of Cd2+ to -SH groups of the membrane is closely related to the induction of these effects. PMID- 4027481 TI - Response and sensitivity of guinea-pig airway muscle preparations to 5 hydroxytryptamine during ontogenesis. AB - Responsiveness (g mm-2) and sensitivity (pD2 value) to 5-hydroxytryptamine (5-HT) were markedly reduced in isolated tracheal and bronchial tissues from guinea-pigs during ontogenesis. Responsiveness of the trachea to 5-HT was depressed much more than that to histamine. Airway preparations from young guinea-pigs of either sex always contracted when exposed to 5-HT, an effect that was blocked by methysergide. Airway muscle preparations from old animals exhibited a wide range of responses to 5-HT, namely, no effect, relaxation or contraction. The contractile effect of 5-HT in tracheal and bronchial preparations from old animals was always blocked by methysergide, whereas, the relaxant effect was not. These results indicate that there are significant alterations in the response to 5-HT receptor stimulation in airway muscle preparations from guinea-pigs during ontogenesis. PMID- 4027482 TI - The effects of dopexamine on the cardiovascular system of the dog. AB - The cardiovascular effects of dopexamine and dopamine were compared in the anaesthetized and conscious dog by the use of intravenous infusions over the dose range 3 X 10(-9) - 10(-7)mol kg-1 min-1. In the anaesthetized dog, dopexamine produced a dose-related fall in blood pressure due to peripheral vasodilatation and a small rise in heart rate and contractility. By contrast, dopamine did not significantly reduce blood pressure but produced a larger dose-related increase in contractility. At the highest infusion rate (10(-7)mol kg-1 min-1) blood pressure and heart rate were increased by dopamine. Dopexamine dilated the renal and mesenteric vascular beds with a potency similar to that of dopamine. Femoral vascular responses produced by both agents were inconsistent but the highest infusion rate of dopamine did produce vasoconstriction. With the aid of selective receptor antagonists (haloperidol, propranolol and bulbocapnine) the vasodepressor activity of dopexamine was shown to be mediated by stimulation of DA2-, beta- and DA1-receptors. The cardiac stimulation and renal vasodilatation produced by both compounds were due to stimulation of beta-adrenoceptors and DA1 receptors respectively. In the conscious dog, intravenous infusion of dopexamine caused a dose-related fall in blood pressure, renal vasodilatation and an increase in cardiac contractility and heart rate. Dopamine also increased cardiac contractility, and renal blood flow due to renal vasodilatation but without affecting heart rate. At the highest infusion rate, blood pressure was increased. Dopexamine and dopamine produced a similar incidence of panting and repetitive licking at 3 X 10(-8)mol kg-1 min-1 and emesis at 10(-7)mol kg-1 min-1, due to stimulation of dopamine receptors in the chemoreceptor trigger zone. Dopexamine produces a different cardiovascular profile from dopamine in the anaesthetized and conscious dog. Both compounds reduce renal vascular resistance, but in contrast to dopamine, dopexamine reduces afterload and produces only mild inotropic stimulation. These differences reflect contrasting activity at adrenoceptors. PMID- 4027485 TI - Lateralization effects in reading pointed and unpointed Hebrew. AB - Hebrew has two forms of spelling, pointed and unpointed. In the pointed spelling, diacritical signs (pointing) are added to consonantal letters to convey vowel information. These are omitted in the unpointed spelling. Since pointing conveys information that is critical for the prelexical derivation of phonology, it was hypothesized that its absence would prove detrimental for left hemisphere (LH) but not for right hemisphere (RH) reading and that, for the former, pointing effects would increase with increasing word length. Three experiments, one involving lexical decision and two involving word pronunciation, yielded little support for these hypotheses; rather, pointing had an overall adverse effect on performance, and this effect tended to be more pronounced for LH reading. In general, however, the results indicated an LH advantage. Since for central vision pointing has been found to aid performance under similar conditions, the results were seen to suggest a distinction between the visual and the phonological effects of pointing: pointing may impair early stages of visual analysis but may aid in the derivation of speech codes. PMID- 4027484 TI - Solubilization and characterization of high and low affinity pirenzepine binding sites from rat cerebral cortex. AB - An apparently monomeric form of the digitonin-solubilized muscarinic acetylcholine receptor from the rat cerebral cortex retains a high affinity of 7 X 10(7) M-1 for pirenzepine. Muscarinic receptor binding sites in the rat cerebral cortex with a low affinity for pirenzepine are solubilized with relatively little change in affinity. The ability of pirenzepine to distinguish between subtypes of muscarinic binding site in the cerebral cortex is manifest in both the membrane-bound and soluble state. PMID- 4027483 TI - Application of the operational model of agonism to establish conditions when functional antagonism may be used to estimate agonist dissociation constants. AB - The operational model of agonism (Black & Leff, 1983) has been used to analyse comparatively functional antagonism and irreversible antagonism as methods for estimating agonist dissociation constants (KAs). A general condition is established in terms of the model parameters which defines the type of experimental interventions at the receptor and the post-receptor level that allow valid KA estimation. It is shown that functional antagonism and other post receptor interventions may produce changes in agonist-concentration effect curves which are qualitatively indistinguishable but quantitatively distinct, from those produced by irreversible antagonism. Experimental data obtained with the guinea pig tracheal strip preparation are in keeping with the theoretical predictions and show how studies using functional antagonism may overestimate agonist affinity. In general, functional antagonism, unlike irreversible antagonism, is in principle an unreliable method for quantifying agonism. PMID- 4027486 TI - The measurement of self-reported stress and arousal. AB - This paper provides further discussion on the measurement of mood using self report inventories. It comments on questions raised by Cruickshank (1984) about the structure and use of the stress-arousal checklist developed by Mackay and Cox (Mackay et al., 1978). PMID- 4027487 TI - Age and individual differences in correct and error reaction times. AB - Rabbitt (1979, 1981) has argued that the slowing of choice RT performance with old age reflects less sensitive control over speed of responding. Based on the finding that old subjects' errors were as fast as young subjects', whereas their correct responses were much slower, Rabbitt suggested that old subjects often overshoot when trying to increase or reduce response speed. Data collected from a different serial, four-choice RT task in this experiment were not, however, consistent with Rabbitt's account. Error as well as correct RTs were longer in old than in young adults, with both showing similar increases with age. A post hoc examination of the aged subjects' data also indicated important individual differences within aged samples. Some subjects' RTs and error rates were no different from those of the young; other subjects' longer RTs and lower error rates were consistent with an increased emphasis on accuracy. PMID- 4027488 TI - Cognitive and affective aspects of boredom. AB - It is argued that previous research may have been mistaken in assuming that monotony in sensory stimulation is a necessary and sufficient cause of boredom. Five investigations are reported which used personal construct theory and repertory grid techniques to investigate three hypotheses: that boredom is associated with subjective monotony, that boredom is associated with a high degree of frustration and that boredom arises when stimulation lacks meaning for the individual. Results supported hypotheses (1) and (2) but no evidence was found to support hypothesis (3). PMID- 4027489 TI - Towards a model of boredom. AB - On the basis of the authors' own research it is suggested boredom may be viewed as having cognitive and affective components. The cognitive component is subjective monotony and the affective component is a high level of frustration. An attempt is made to integrate the evidence supporting this view of boredom with other evidence from the literature to present an integrated model of boredom in which the roles of personality, situational and task characteristics influencing boredom are outlined. Psychophysiological changes occurring during the performance of boring tasks are examined. It is argued that the nature and extent of changes in heart rate and heart-rate variability are not a consequence of boredom but of a task feature (mental load). It is concluded that no clear psychophysiological component of boredom can be detected at present. PMID- 4027490 TI - Lateralized processes in face recognition. AB - In this paper a model is presented in which face recognition is analysed into several stages, each of which may be independently lateralized. Evidence is reviewed which suggests that lateralization is important at all stages of processing a face. Early visuospatial processing, and the creation and comparison of facial representations, appear to be carried out more efficiently by the right hemisphere. Comparisons based on discrete, namable features of faces may yield a left hemisphere advantage. It is also proposed that faces may activate semantic information, including names, more efficiently in the left hemisphere. The model is useful in resolving inconsistencies in the degree and direction of asymmetries found in face-recognition tasks. Suggestions are also made for future research. PMID- 4027491 TI - Australian Rules football: an anthropometric study of participants. AB - Anthropometric measurements and personal data were collected from 119 Australian Rules footballers from Victoria. A top level professional league team, a second level association team, and an A-grade amateur association team were observed, representing three levels of ability. The profile of physical features of these athletes at the beginning of the season is presented. A gradation of body size was observed between teams. The players in the top level team were slightly taller and heavier than those in the other teams. They had less body fat, as shown by lesser skinfold thicknesses, a smaller percentage body fat as determined by prediction equations, and a greater fat-free mass. The intermediate level team showed an intermediate level of body fat and the lower level team had the highest proportion of fat. PMID- 4027492 TI - Outcome of sports injuries treated in a casualty department. AB - The present investigation analyses 2493 patients with a sports injury treated in a casualty department during a one-year period. Of the patients 73% were men, the age of the patients averaging 26 years and the mean follow-up time was 24 months. Soccer and indoor ball games caused 24% and 23% of the injuries respectively, these being followed by injuries in ice hockey in 14%. Track and field injuries scored low with 2% out of all injuries. Injuries to the lower extremity predominated. At follow-up, ligamentous injuries of the lower extremity were the major cause of discomfort. Further, in the group of patients with persistent discomfort 36% had suffered a fracture or a dislocation, 13% a contusion and 10% a wound. The mean period of sports incapacity after a sustained injury was 3 weeks. In track and field events the injury seldom disturbed training for more than one week, but in soccer, indoor ball games, skiing and skating the mean sports incapacity period varied between 6 and 3 weeks. Out of the total injured, 2% had to give up their sports activity completely. An injury of the lower extremity demanded on average 4 weeks' rest, an injury of the upper extremity and the trunk 2 weeks and injuries of the head and neck one week's rest. According to the present investigation sports injuries were in the majority of cases of a relatively benign nature and sick leave from work seldom exceeded 2 weeks. PMID- 4027494 TI - Serum lipids: interactions between age and moderate intensity exercise. AB - The purpose of this study was to examine relationships between age and selected serum lipids and lipoproteins in women before and after a physical fitness programme. Twenty females 27-59 years of age who had participated in the Purdue University Physical Fitness Programme were selected and placed into one of two groups: "junior" (mean age 34, all under 40 yrs) or "senior" (mean age 50, all over 43). A two way factorial design was used to study differences in serum triglycerides (TG), total cholesterol (TC), low density lipoprotein cholesterol (LDLC), high density lipoprotein cholesterol (HDLC), and the risk ratios TC/HDLC and LDLC/HDLC associated with physical fitness and the eight month physical fitness programme. The ability of the biochemical variables to discriminate between the age groups was investigated using discriminant function analyses. The analyses of variance indicated that although the two age groups were matched on the basis of a multivariate physical fitness score (Ismail et al, 1965) the older group was heavier (p less than 0.05), and had higher systolic and pulse pressures (p less than 0.05). Both groups increased their physical fitness score from pre to post programme (p less than 0.01). No significant age related biochemical differences were noted in the univariate analyses; however, in the discriminant function analyses the biochemical variables significantly discriminated between the two groups before, but not after the programme. A decrease in serum triglycerides was observed in the more highly fit women in each age group. These findings suggest that moderate levels of physical activity may help to counteract some of the undesirable changes in the lipid profile associated with age. PMID- 4027493 TI - Does exercise alter anaerobic threshold in coronary artery disease during beta blockade? AB - The effect of propranolol on cardiac patients undergoing exercise training is reported to increase exercise tolerance and maximum oxygen uptake (VO2 max) but its effect on anaerobic threshold (AT) is unknown. It was the purpose of this study to determine the role of exercise training with propranolol on AT in patients with coronary artery disease (CAD). Eight men and one woman with significant (CAD) were selected for this study. Each patient completed a maximum treadmill stress test (MTST) following the Bruce protocol on propranolol 40-160 mg/day as a control study. Cardiorespiratory variables were measured at rest and at each stage of the treadmill test. These patients underwent an exercise training programme for 12-16 weeks on the same dose of propranolol. Training sessions were for a minimum of 30-40 minutes, 3 times a week, with training heart rate of 75%-85% of the pretraining peak heart rate. Training heart rate ranged from 98 to 128 beats/min. They were retested with a MTST after the training programme, on the same dose of propranolol. AT was calculated noninvasively by measuring respiratory variables every 30 seconds in relation to work increment. AT was identified by measuring the time course of VE, VCO2, VE/VO2, etc. in relation to incremental work. The mean values of VO2, O2P and % VO2 max at AT before and after training on propanolol were as follows: VO2 = 1.43 L/min +/- .25 and 1.86 L/min +/- .44, O2P = 14.35 +/- 2.40 and 18.73 +/- 4.00 ml/beat, % of VO2 max = 68.20 +/- 6.31 and 73.59 +/- 5.84. The mean changes of VO2 O2P, and % of VO2 max were + 0.43 L/min +/- 0.20 (P < .003), + 4.38 +/- 2.55 (P < .003) and +/- 5.07% +/- 4.84 (P < .001). After exercise training on propanolol, the mean peak exercise tolerance time and absolute VO2 max increased by 2.8 min (from 9.0 to 11.8 min) (P < .001) and 22.7% (P < .007), respectively. We conclude that the increase in anaerobic threshold in patients with coronary artery disease may be due to improvement in VO2 max, increased stroke volume, and peripheral O2 extraction. PMID- 4027495 TI - Avulsion fracture involving the body of the patella. AB - A report on an unusual transverse fracture through the body of the patella in a 13 year old high jumper is presented. The clinic features and treatment of the more usual avulsion injury of the patella is discussed. PMID- 4027496 TI - Sports injuries in adolescent boarding school boys. AB - A survey is presented of 346 sports injuries admitted to the Eton College Sanatorium between 1971 and 1982. The incidence of injury was lowest in 13 year olds perhaps because of their lighter weight. The injuries were classified into four groups--minor head injury, soft tissue injury, fractures and dislocations, and eye injury. Football caused 75 per cent of all injuries except eye injury where it accounted for only a third. Comparison of the incidence of injury at the three types of football played at Eton--Rugby, Association and Eton--showed Rugby football to be the most dangerous and Eton football the safest game. Advice on the management and prevention of injury is given. PMID- 4027497 TI - Rugby football injuries, 1980-1983. AB - The injuries sustained by the boys at one English public school have been recorded and analysed by age, experience, position, phase, duration of the game and of the season. Few injuries have been serious. Detailed reference is made to concussion, injuries from collapsed scrums and injuries of the cervical spine. The paper emphasises that the tackle leads to most injuries. This paper presents the Rugby football injuries sustained by the boarders of Rugby School in the four seasons 1980-1983. The injury rate was 194 per 10,000 player hours, compared with the rate of 198 per 10,000 player hours for the thirty seasons 1950-1979 (Sparks, 1981). Tables I-VI list the injuries by different criteria. Table VII lists the sites of injury; Table VIII the time off Rugby football after injury; Table IX lists some of the more important injuries; Table XI summarises the playing results of the various school teams; Table XIII compares some of the Rugby School figures with those recorded in the Accident and Emergency Department of Christchurch Hospital during the 1979 New Zealand Rugby football season (Inglis and Stewart, 1981); Table XIV records information on three aspects of Rugby football that have occasioned much recent concern, viz:--Time off playing after concussion, injuries caused by collapsed scrums and neck injuries. PMID- 4027498 TI - A laboratory running test: metabolic responses of sprint and endurance trained athletes. AB - A laboratory-based sprint running test has been devised to examine the performance characteristics and metabolic responses of an individual to 30 seconds of maximal exercise. A non-motorised treadmill was used so that the individual was able to sprint at his own chosen speed and also to vary his speed as fatigue occurred. The treadmill was instrumented so that the chosen speeds as well as the equivalent distance travelled could be monitored by micro-computer throughout the test. The test-retest reliability of the procedure was investigated with 14 recreational runners who performed the test on different days. A good correlation (r = 0.93) was found between the values obtained for peak running speeds on the two occasions. In an attempt to establish whether or not this test could be used to identify the differences in the performance characteristics of highly trained individuals, the responses to the test of eleven sprint trained and eleven endurance trained athletes were examined. The sprint trained athletes covered a greater distance (162.2 +/- 5.95 m vis 153.51 +/- 12.32 m; p less than 0.01) and had higher blood lactate concentrations (16.52 +/- 1.23 mM vis 12.98 +/- 1.77 mM; p less than 0.01) than the endurance trained athletes. Therefore this laboratory sprint running test offers an additional way of investigating human responses to brief periods of high intensity exercise. PMID- 4027499 TI - Predictability of VO2 max from submaximal cycle ergometer and bench stepping tests. AB - The predictability of the maximal oxygen uptake (VO2 max) was studied using progressive and steady state protocols for cycle ergometry and bench stepping. The subjects were 12 healthy men, 23-58 years old. Prediction of VO2 max was made by extrapolation of the heart rate and O2 uptake at several sub-maximal work loads using the least squares regression technique. The four sub-maximal procedures underestimated the measured VO2 max by between 0.13-0.55 l.min-1. The differences between the measured and predicted values were statistically significant for the tests involving the steady state protocol. The correlation coefficients between the predicted VO2 max for each of the submaximal tests, and the measured VO2 max, were significant at the .05 level. The results indicate that for a group of male subjects VO2 max can be predicted using the progressive protocol on either the cycle ergometer or stepping bench. Individual predictions are liable to considerable error. PMID- 4027500 TI - Mouthguards, an evaluation of two types for Rugby players. AB - At the beginning of the 1983/84 Rugby season a dental examination was carried out on 120 players, 55 of whom were fitted with the mouth-fitted type of mouthguard and 65 the laboratory-made type of mouthguard. At the end of the season only 98 players were available for the completion of the study. A further dental examination showed that there was no damage to the teeth when either type of mouthguard was worn. Variations in the attitudes of the players to each type of mouthguard were also recorded. PMID- 4027501 TI - Orofacial injuries and mouthguards: a study of the 1984 Wallabies. AB - As mouthguards provide protection of the teeth, jaws, adjacent soft tissues and also protect the brain against concussion following impacts to the mandible, the use of mouthguards in contact sports is strongly recommended. It is therefore essential to gauge regularly the use of mouthguards in the various contact sports at all levels of competition. Of the 30 members of the 1984 Australian Rugby Union Touring Team (the Wallabies), 80% wore mouthguards and of these, 75% believed that wearing mouthguards should be made compulsory for Rugby players. A comparison of these and other findings is made with previous studies in Rugby, and also with a similar study of the 1984 Great Britain Rugby League Touring Team. PMID- 4027502 TI - Age, height and weight of female Olympic finalists. AB - Age, height and weight are intricately related to performance in a specific sporting activity. Optimum standards derived from 32 female Olympic finalists from two jumping events are listed as a sample from a much larger set of 824 finalists from 47 events. An example of variation is that high jumpers are taller by 6.3 cm and younger by 2.9 years than long jumpers. Conversely, considerable variation in body weight is shown for a group of finalists all with a height of 171 cm. The weights of these finalists range from 56 kg for a 400 m runner to 85 kg for a discus thrower. Many other events are listed between these examples and a number of events are found to share the same combination of height and weight (height 171 cm, weight 59-62 kg) swimming freestyle and medley, 200 m run, rowing, canoeing, volleyball and handball. These findings are expected to be of use for potential champions looking for optimum standards in specific events. They are also of use for trainers counselling athletes in the most appropriate selection of the event befitting her physique. Many sporting activities are found to be seriously biased in favour of the taller members of the population. This is a cause for concern as is the need for some remedial action. PMID- 4027503 TI - Marathon running and muscle fasciculation. PMID- 4027504 TI - Family history of renal stones in recurrent stone patients. AB - A survey was carried out on the family history of renal stones among 380 patients in an out-patient stone clinic, most of whom had experienced frequent recurrences. In 55.4% of patients at least one first-degree relative had experienced renal stones. A positive family history was more common in females (64.7%) than in males (51.0%) and was particularly apparent in those who had multiple recurrences. It was also significantly more common in female patients with evidence of renal tubular defects (incomplete forms of renal tubular acidosis). Among the ordinary stone patients 18% of the fathers and 8% of the mothers had also formed renal stones. The corresponding figures for female stone patients with renal tubular defects were 40 and 33% respectively. These findings indicate that tubular dysfunction could be an inherited trait that predisposes to the formation of renal stones. Hypercalciuria or hyperuricosuria was not over represented among stone formers with a positive family history. PMID- 4027506 TI - Immunohistological detection of T antigen and ABH blood group antigens in upper urinary tract tumours. AB - The status of T antigen was assessed by means of peanut agglutinin (PNA) used in an immunoperoxidase technique, and the status of ABH blood group antigens was determined by the specific red cell adherence (SRCA) test. Thirty-eight patients with upper urinary tract tumours were examined. Our data indicated that T antigen status did not correlate with conventional prognostic indicators such as grade and stage of tumour and survival of patients, while the expression or deletion of ABH blood group antigens did correlate well. It was concluded that ABH blood group antigen determination might provide a useful prognostic probe in upper urinary tract tumours should it find clinical application. PMID- 4027505 TI - Allopurinol treatment of renal calcium stone disease. AB - Thirty-one calcium stone patients were treated with 300 mg allopurinol daily during a mean follow-up period of 2 years. They were also given advice on diet and fluid intake. The effects on the recurrence rate of stones were compared with the effects on the recurrence rate in 43 calcium stone patients who were given similar advice on diet and fluid intake but were not treated with allopurinol. In both groups there was a reduction in the recurrence rate but no difference between patients treated with allopurinol and the control group. Some patients with only hyperuricosuria prior to treatment seemed to benefit from allopurinol treatment, whereas those with hypercalciuria continued to form stones with the same frequency. Allopurinol treatment in calcium stone disease appears less effective than treatment with thiazides, magnesium hydroxide or orthophosphate. PMID- 4027507 TI - Malignant phaeochromocytoma. AB - Malignant phaeochromocytoma is a rare tumour and experience in its management is therefore limited. Five patients are discussed in whom the development of metastases was associated with rapidly progressive disease. PMID- 4027509 TI - A simple loop catheter for ureteric calculus retrieval. AB - The fabrication and use of a simple looped catheter for ureteric stone retrieval are reported. In a series of 46 patients the loop was passed successfully in 28 and the stone dislodged in 20 (71.4%). This device can be made by any urologist, using cheap, readily available materials. Complications are few and the success rate is high. PMID- 4027508 TI - Selection of operative procedure for circumcaval ureter (type I). A rational approach. AB - The surgical treatment of circumcaval ureter (type I) should eliminate the ureteric obstruction which is of variable causation. At operation, the aetiology of the obstruction can be determined by inspection of the extent of ureteric dilatation, perfusion-pressure study and calibration of the lumen. Using this approach, the cause of the obstruction was found to be nonstenotic intrinsic obstruction of the retrocaval segment in two cases of type I circumcaval ureter. In these patients, resection of the obstructing segment and uretero-ureterostomy were carried out. The third patient had pelviureteric junction stenosis which was treated by dismembered pyeloplasty after ureteric relocation. PMID- 4027510 TI - Unilateral ureteric reimplantation for primary vesicoureteric reflux in children. A policy re-evaluated. AB - Fifty-one children had unilateral ureteric reimplants for primary vesicoureteric reflux over an 11-year period. Reflux was abolished in 50 patients but in 8 (15.7%) it developed or became worse on the contralateral side. An isotope renal scan (99mTc DMSA) was carried out in 15 of the 18 patients who had grossly scarred or dysplastic kidneys. Thirteen of these had less than 22% of total function coming from the affected kidney and seven had less than 10% of their total GFR coming from the kidney whose ureter had previously been reimplanted. Five of these children have undergone nephrectomy and it is felt that this would have been a better initial procedure. No patient was hypertensive at the conclusion of the study. PMID- 4027511 TI - Low pressure/low flow voiding in younger men: psychological aspects. AB - Low pressure/low flow voiding in young and middle-aged males in the absence of outflow tract obstruction has been reported as being associated with anxiety and a high incidence of dyspepsia. To assess objectively the psychological basis of this condition, an unselected group of 50 men aged 25 to 55 years was evaluated by psychiatric interview, questionnaires and urodynamic tests. In addition, patients involved in an earlier study were psychologically evaluated. Low pressure/low flow voiding was demonstrated in three (6%) of the new patients. This voiding pattern was related to a long preceding history, stress-dependent symptoms and difficulty in voiding in public urinals. When compared with a control population, the experimental group scored significantly higher on measures of psychoneurosis. It is recommended that surgery be avoided in these patients and that simple behavioural therapy may be most appropriate. PMID- 4027513 TI - Perineal nerve damage in genuine stress urinary incontinence. An electrophysiological study. AB - Twelve patients with genuine stress incontinence of urine were investigated using manometric and electrophysiological techniques. All were shown to have slowed conduction in the perineal branch of the pudendal nerve which innervates the periurethral striated sphincter muscle. The mean perineal nerve terminal motor latency in these patients was 3.9 +/- 0.8 (ms) and in 20 age and parity matched control subjects was 2.0 +/- 0.2 (ms) (P less than 0.001). These results are consistent with a neurogenic factor in patients with genuine stress incontinence of urine which may have implications regarding selection of patients for surgery to restore urethral competence. PMID- 4027512 TI - Atropine blockade of nerve-mediated stimulation of the human detrusor. AB - The effect of atropine on the isometric contractile response of isolated human detrusor muscle strips to electrical field stimulation has been studied. A 94.1% reduction in the response in the presence of tetrodotoxin demonstrated the neuronal nature of the stimulus. Atropine caused a 92.7% inhibition of the response. It was concluded that the nerve-mediated stimulus in human detrusor is cholinergic in nature and that "atropine resistance" does not occur in man. PMID- 4027514 TI - Adenomatous metaplasia (nephrogenic adenoma) of urothelium. An analysis of 70 cases. AB - A retrospective analysis of 70 cases of adenomatous metaplasia seen in the St Peter's Hospitals over a 15-year period has been carried out. The lesions occurred at all ages (7-81 years) and in both sexes (51 males, 19 females) and were found throughout the urinary tract from pelvis to urethra. In the pelvis and ureter the finding was usually an incidental one in association with stones or chronic inflammation; ulceration was a frequent accompaniment. Most vesical and urethral lesions followed a surgical procedure months or years previously, the patients re-presenting with haematuria or irritative bladder symptoms. The endoscopic appearances varied but there was often a striking correlation between the location of the lesions and the site of previous surgery. The association of adenomatous metaplasia with ulceration and previous surgery leads us to suggest that it is merely an unusual response to wound healing and attempts to treat it by diathermy resection are, therefore, likely to meet with limited success. Cystoscopic follow-up of persistent lesions gives no reason to suppose they are pre-malignant. PMID- 4027515 TI - Chemotherapy before radiotherapy for T3 bladder cancer. A pilot study. AB - Seventeen patients with stage T3 bladder cancer were treated in a pilot study of initial chemotherapy (four courses of cyclophosphamide, methotrexate and 5 fluorouracil) followed by megavoltage radiotherapy 6000 cGy) to the bladder. Chemotherapy was well tolerated and did not lead to any increase in toxicity from the radiotherapy. Assessment of response in all cases was not possible because of the variable extent of the initial biopsy. Of the 12 patients in whom assessment was possible, there was no objective change in 9 (4 cases of T3a; 5 cases of T3b) and there was objective evidence of disease progression in 3 (2 cases of T3a; 1 case of T3b). Thirteen patients have now died and the median survival for patients in this study was 27 months, with a 3-year survival rate of 26%. Three patients died with recurrence in the pelvis, 5 with both local and metastatic disease, 2 with metastases only, and 3 from other causes. These data indicate that this particular form of chemotherapy given as initial treatment for T3 bladder cancer does not appear to lead to an improvement in the results obtained from radiotherapy alone. PMID- 4027516 TI - Vesico-uterine fistula. AB - Nine cases of vesico-uterine fistula caused by injury to the bladder at Caesarean section or by rupture of the uterus and bladder following obstructed labour are described. Symptoms depend on the level of the lesion, menstruation into the bladder and menouria occurring when the fistula is above the internal cervical os: whatever the level, most patients with vesico-uterine fistula present with incontinence of urine. A transperitoneal approach appears to give better results than a transvesical repair. PMID- 4027517 TI - Hyponatraemia following transurethral resection of the prostate. AB - In a prospective study of 100 patients undergoing transurethral resection, changes in serum sodium were estimated during the per-operative and post operative periods. The weight of prostate resected and the volume of irrigant fluid used influenced the changes in serum sodium. In 93 patients these changes were not statistically significant. In only seven patients were significant falls in serum sodium recorded, in one case to a level of 103 mmol/l. All seven exhibited the clinical features of the transurethral syndrome and there was one post-operative death which we attributed to it. The TUR syndrome undoubtedly exists and its incidence in this series was 7%. Its pathogenesis and clinical management are discussed. PMID- 4027518 TI - Direct vision internal urethrotomy in the treatment of urethral fistulas due to urethral strictures. AB - Five cases of urethral fistula--three with single and two with multiple fistulous tracts--were treated by optical urethrotomy. All of the fistulas healed completely. PMID- 4027519 TI - Carcinoma of skin of penis. AB - Like the Jews, the Ibos or Igbos of Nigeria ritually circumcise males on the eighth day of birth. A retrospective review of approximately 15,000 surgical specimens collected from this ethnic group over a period of 13 years revealed 32 cases of carcinoma of the prostate but only 4 cases of penile carcinoma. One tumour arose on the glans penis. This localisation pattern suggests that, in circumcised males, smegma-induced squamous carcinoma of the glans can be abolished but not the ordinary squamous carcinoma that can develop by chance on the rest of the penis as well as on the glans. International urology would benefit from careful documentation of squamous carcinoma affecting various parts of the neonatally circumcised penile skin. PMID- 4027520 TI - Male genital injuries from external trauma. AB - External trauma from a variety of causes, some unusual and bizarre, affect the male genitalia. Certain injuries are more common, have more severe consequences, or their management may be controversial. Seventy male genital injuries from external trauma are reported and include vacuum cleaner injuries, fracture of penis and the tourniquet syndrome. PMID- 4027522 TI - Repeated pregnancies following in vitro fertilisation therapy in cases of male infertility. PMID- 4027521 TI - Single sample estimates of renal clearances. PMID- 4027523 TI - Round headed sperm. PMID- 4027524 TI - Distalgesic abuse and retroperitoneal fibrosis. PMID- 4027525 TI - Carcinoma in a post-diversionary bladder. PMID- 4027526 TI - Use of the metal stylet of a ureteric catheter for ureteric meatotomy. PMID- 4027527 TI - Hodgkin's disease: is staging laparotomy necessary? PMID- 4027528 TI - The outcome following sphincter-saving resection and abdominoperineal resection for low rectal cancer. AB - The introduction of new techniques has enabled more patients with low rectal carcinoma to undergo sphincter-saving resection (SSR). This policy, however, has provoked controversy concerning the adequacy of excision and fear of increased rates of recurrence compared with abdominoperineal resection (APER). We have therefore compared our results of SSR for low and mid-rectal cancers performed between 1978 and mid 1982 with those obtained with APER before this period. One hundred and fifty-nine patients presented with tumours between 3 and 12 cm from the anal verge; 153 (96 per cent) underwent resection, of whom 46 (30 per cent) had disseminated disease. One hundred (68 per cent) underwent SSR, 33 (22 per cent) had an APER and 16 (10 per cent) had a local procedure. Operative mortality was 4 per cent following APER and 7 per cent after SSR (n.s.). Patients were followed for a mean of 4.6 years (range 2-6 years), only four (2.5 per cent) being lost to follow-up. The incidence of recurrence after radical SSR (n = 74) was compared with the historical control group which underwent radical APER, the two groups being matched for Dukes' stage and height of the lesion. After 2 years, local recurrence cumulative rates were 13.6 per cent after SSR and 18.8 per cent after APER. Distant recurrence rates were 14.5 and 20 per cent respectively. Ten patients (13.5 per cent) died of their disease within 2 years of a radical SSR, 15 (15 per cent) after radical APER. Corrected 5-year survival and recurrence rates were similar. Thus, SSR does not appear to carry an increased risk of recurrent disease compared with APER after an equivalent follow up period. PMID- 4027529 TI - The results of surgical treatment of cancer of the rectum by radical resection and extended abdomino-iliac lymphadenectomy. AB - At St Mark's Hospital survival after radical surgery for cancer of the rectum has not changed significantly over the past 30 years. The technique of extended abdomino-iliac lymphadenectomy was developed in an attempt to improve prognosis in patients considered to have particularly unfavourable tumours. Between 1960 and 1981 the technique was used in 75 patients with a single adenocarcinoma of the rectum. Two patients died postoperatively and 52 patients developed complications; a mortality and morbidity similar to those seen after conventional surgery at this hospital. Five-year survival rate showed no improvement over that achieved by conventional techniques; disappointingly this was also the case for patients with Dukes' C1 tumours. The results of this study suggest that an improvement in survival in patients with cancer of the rectum is unlikely to be achieved by any extension of conventional radical surgery. PMID- 4027530 TI - Anal implantation metastasis from carcinoma of the sigmoid colon and rectum--a risk when performing anterior resection with the EEA stapler? PMID- 4027531 TI - Acral (volar-subungual) melanoma. AB - Acral melanoma occurs in the volar surface of the hands, feet, fingers, toes and subungual sites. Recently it has been recognized as a distinct entity with characteristic clinical and pathological features. Of our 340 patients with malignant melanoma, 24 (7 per cent) had acral melanoma. Sixteen were in the plantar skin, two in the palms and six in the nailbed. The delay in diagnosis was 6 months to 5 years and most of the patients presented with large neglected tumours. Fourteen lesions had histological features consistent with acral lentiginous melanoma - a unique pattern to this area. Fourteen patients were in clinical stage I at diagnosis, seven in stage II and three had distant metastases (stage III). The treatment was mainly surgical. Palmar-plantar lesions were widely excised. One patient underwent below-knee amputation. Lesions of the digits were treated by amputation of the affected toe. Fourteen of the patients underwent either prophylactic or therapeutic lymph node dissection. In 9 of them, regional metastases were found. In patients with advanced disease chemotherapy was added. Three patients had isolated limb perfusion. Fourteen patients died of metastatic disease within 1-5 years. Four are alive but have metastatic spread. Six patients are disease-free, one to 4.5 years following diagnosis. PMID- 4027532 TI - The value of staging and serial follow-up investigations in patients with completely resected, primary, cutaneous malignant melanoma. AB - The purpose of this study was to determine the value of staging and serial follow up investigations in newly diagnosed patients with completely excised primary cutaneous malignant melanoma. We reviewed the records of the 393 patients with completely excised primary malignant melanoma who were referred to the Ontario Cancer Institute and the Toronto-Bayview Regional Cancer Centre between 1 January 1978 and 31 March 1982. Initial investigations included history and physical examination in all 393 patients, complete blood count (199 patients), liver function tests (198 patients), urinary melanins (159 patients), chest X-rays (345 patients), whole lung tomography (182 patients), radionuclide liver-spleen scans (207 patients), and bone scans (116 patients), bipedal lymphangiograms (78 patients), CT scans of the chest (59 patients), and CT brain scans (51 patients). The clinical stage of ten patients was changed as a result of history and physical examination or lymphangiogram. All other investigations failed to detect metastatic melanoma. Follow-up investigations included history and physical examinations, complete blood counts, liver function tests, radionuclide liver spleen and bone scans. History and physical examinations, chest X-rays and patients' awareness of abnormalities were responsible for detection of subsequent melanoma recurrences. All other tests failed to identify metastatic melanoma at the time of its occurrence. Therefore, we recommend that initial staging investigations be limited to history and physical examination with clinical photographs, and baseline chest X-ray. We recommend that subsequent follow-up include only history and physical examinations and chest X-rays. PMID- 4027533 TI - Gastric surgery and the risk of subsequent colorectal cancer. AB - A matched case control study has been conducted in order to determine whether an association exists between gastric surgery and the subsequent development of colorectal carcinoma. Two hundred and eighty-nine patients (151 women and 138 men) presenting with large bowel cancer have been studied. Case controls were matched according to age, sex and date of admission. The case notes of each patient in the study were reviewed to determine the prevalence of peptic ulceration and gastric surgery. Significantly more patients with colorectal carcinoma had undergone gastric surgery P less than 0.05, although the prevalence of peptic ulceration was similar in both groups. Colorectal carcinoma is more common in patients who have undergone gastric surgery for benign peptic ulcer disease than in the general population. PMID- 4027534 TI - Gastric emptying after anterior lesser curve seromyotomy and posterior truncal vagotomy. AB - Anterior lesser curve seromyotomy with posterior truncal vagotomy (ASPTV) provides a simple, safe and expeditiously performed method of denervating the parietal cell mass, whilst preserving the pylorus. Dumping and diarrhoea are uncommon after this procedure. Gastric emptying has been assessed after ASPTV and other elective operations for duodenal ulcer. Liquid and solid phase gastric emptying studies were performed in control subjects (17), patients before and at least six months after ASPTV (14), vagotomy and pyloroplasty both without (8) and with (6) diarrhoea, vagotomy and gastroenterostomy (11), and Polya gastrectomy (7). There was no delay in emptying time for liquids or solids between ASPTV patients and controls. With the exception of an increase in the early emptying of liquids (P = 0.02) after ASPTV, gastric emptying was not different from normal. After truncal vagotomy and pyloroplasty in patients without diarrhoea the gastric emptying of solids, but not of liquids, was markedly increased (P = 0.00001), whereas in those with diarrhoea both liquid and solid phase emptying were markedly increased (P less than 0.001). When gastroenterostomy was used as the drainage procedure both phases of emptying were increased. After Polya gastrectomy, both early and late emptying of liquids and solids were increased (early phase P less than 0.05, overall emptying P less than 0.001). PMID- 4027535 TI - Partial gastrectomy with Roux-en-Y reconstruction in the treatment of persistent or recurrent oesophagitis after Nissen fundoplication. AB - The results of partial gastrectomy with Roux-en-Y reconstruction in the treatment of persistent or recurrent oesophagitis after failed Nissen fundoplication in six patients were analysed. There were no postoperative deaths. Postoperative complications (pneumonia and atelectases, postoperative ileus) developed in three patients. The results were evaluated by clinical and endoscopic examination 1 to 3.5 years after the operation. Clear clinical and endoscopic improvement was observed in five of the six patients. In the remaining patient the procedure failed to prevent progression of the oesophagitis with development of a Barrett's oesophagus. The results suggest that a partial gastrectomy with Roux-en-Y reconstruction is an effective and safe procedure in the treatment of persistent or recurrent oesophagitis after failed Nissen fundoplication. PMID- 4027536 TI - Retroperitoneal tumour infiltration detected by bone scanning in patients with infiltrating lobular carcinoma of the breast. AB - Radionuclide bone scans performed in some patients with carcinoma of the breast showed abnormal retention of isotope in the renal pelvis which developed and progressed during the period of follow-up after mastectomy. This phenomenon was seen in 15 of 30 patients with infiltrating carcinoma of the breast (ILC) but in none of 29 with infiltrating duct carcinoma (IDC). Autopsies were performed in eight of the patients with ILC and three of those with IDC. Diffuse retroperitoneal and ureteric infiltration was seen in seven (88 per cent), with ILC and none with IDC. These data suggest that this scan abnormality is an indicator of retroperitoneal spread by ILC. PMID- 4027537 TI - Risk factors and clinical data related to oestrogen receptor status in women presenting with breast cancer. AB - Oestrogen receptor (ER) content was measured in 257 patients presenting with 'operable' breast cancer. Difference in age, menopausal status, parity, age at first pregnancy, breast feeding habit and details of past and family history were compared with oestrogen receptor status. The symptoms and their duration together with the extent of the disease both clinically and pathologically were also compared with receptor status. Association both for increasing age and postmenopausal status was found when oestrogen receptors were present in the primary tumours in significant quantities. No separation between the effect of age and menopausal status on oestrogen receptor status could be distinguished. No relationship was demonstrated between oestrogen receptor status and the other clinical and pathological factors examined. PMID- 4027538 TI - A complication of minitracheostomy. PMID- 4027539 TI - Pilonidal sinus excision--healing by open granulation. AB - A prospective study is reported of 100 pilonidal sinus excisions healing by open granulation. Delays in healing appeared to be due to infection, particularly by anaerobic bacteria. Comparisons are made between three groups studied consecutively - 30 wounds not treated with antibiotics, 20 given a fixed two-week course of metronidazole and 50 managed flexibly. In this last group, wound management was determined by clinical appearance; 24 wounds were clinically healthy throughout and received no antibiotic while 26 looked unhealthy initially or after an interval and were treated with metronidazole, supplemented in some cases with erythromycin. The best results were obtained in the group managed flexibly. It is considered that the problems of delayed healing are due to excisions which leave a wound of a shape ill-designed to maintain good drainage. Unhealthy wounds should be re-shaped if possible and treated early with a combination of metronidazole and erythromycin. PMID- 4027540 TI - Caroli's disease: successful management using permanent-access hepaticojejunostomy. PMID- 4027541 TI - Oxygen tension on the skin of the gaiter area of limbs with venous disease. AB - We examined the levels of oxygen on the skin of the gaiter areas of limbs with venous disease using a Roche Transcutaneous pO2 Monitor to determine whether hypoxia contributes to the skin changes and ulceration associated with severe venous disease. We studied patients with superficial varicose veins and no skin changes (Group 1: n = 25), patients with skin changes and healed ulcers (Group 2: n = 15), and an age matched normal control group (controls: n = 25). TcpO2 measurements were taken 5 cm above the medial malleolus with the limb both horizontal and vertical using a Roche Transcutaneous pO2 Monitor. A standard heel raising test using a Medisonics Photoplethysmograph indicated the degree of venous insufficiency present. Results show that Group 1 patients and controls have similar skin oxygen levels (Group 1: TcpO2 66.48 + 14.12 mmHg; controls: TcpO2 61.60 +/- 11.02 mmHg) whereas those with skin changes and ulceration have significantly lower oxygen levels (Group 2: TcpO2 46.57 +/- 9.70 mmHg, t = 4.29, P less than 0.001). Group 2 patients did not show a significant rise in TcpO2 levels in the standing position whereas Group 1 patients and controls did (t = 2.6, P less than 0.02). PPG post-exercise recovery times confirmed differences between the three groups. These findings show that significant skin hypoxia occurs on the gaiter area of limbs with severe venous disease and support the concept of an oxygen diffusion block. PMID- 4027542 TI - Giant ulcer of the oesophagus with erosion of the aorta- successful treatment with aortic suture secured by an omental graft and oesophagectomy. PMID- 4027543 TI - Surgical management of Caroli's disease involving both lobes of the liver. PMID- 4027544 TI - Aganglionosis of the entire bowel: four new cases and review of the literature. PMID- 4027545 TI - Malignant masquerade at the hilum of the liver. AB - Eight patients with biliary obstruction and a pre-operative diagnosis of a neoplastic lesion at the confluence of the hepatic ducts were found postoperatively to have benign disease. Cholangiography was highly suggestive of a malignant stricture in all patients. Angiography performed in six patients indicated that the lesions were potentially resectable. Seven patients underwent elective surgery; in six the ductal confluence including the lesion was removed, without mortality. Six patients are alive, five of them totally asymptomatic, in a median follow-up of 32 months. Many patients with hilar strictures are treated for what appears radiologically to be a neoplastic lesion. Since treatment often involves the placement of an endoprosthesis or palliative surgery, without histological diagnosis, some of these patients with benign disease are likely to be treated inappropriately, unless they are considered for a curative resection. PMID- 4027546 TI - Management of retroperitoneal haematoma following penetrating trauma. AB - Experience with the management of 106 consecutive patients found to have a retroperitoneal haematoma (RH) at laparotomy for penetrating trauma over a 2-year period is reviewed. Three types of retroperitoneal haematoma are recognized: Type I (central), Type II (flank) and Type III (pelvic). Type I RH was present in 22 patients as a result of injuries to the inferior vena cava (9), the aorta (5), the pancreas and duodenum (5), the portal vein (2), and to both aorta and inferior vena cava (1). Fourteen patients died (63.8 per cent) representing 70 per cent of all deaths in the series. Type II RH was seen in 73 patients. Thirty two were stable and the perinephric fascia was not opened with no morbidity or mortality. Forty-one were explored: 15 on pre-operative evidence of renal injury which was confirmed at laparotomy. In the remaining 26 a stable haematoma was explored and no significant lesion found. It is considered that in 45 of 73 Type II RH (61.0 per cent) exploration was unnecessary. Five patients died (6.8 per cent). Type III RH was found in 11 patients and was due to iliac vessel injuries. Two patients died. In conclusion Type I and III RH should be routinely explored. Stable Type II RH discovered at laparotomy should be explored selectively based on pre-operative clinical and radiological assessment of renal injury. PMID- 4027547 TI - A survey of registrars undertaking general surgical research in the United Kingdom on 1 October 1983. AB - Data, concerning general surgical research, was obtained by means of a questionnaire from 103 junior surgeons undertaking full-time research. Most posts appeared to be adequately funded, though many respondents sustained a loss of salary on appointment. Less than half the posts were advertised in the national medical journals. All but one respondent were submitting their research for a higher degree. The majority felt that they were well supervised: a minority (24 per cent) were poorly supervised. The enjoyment of research and confidence of obtaining a higher degree were related to the standard of supervision. PMID- 4027549 TI - Acute appendicitis in the elderly. PMID- 4027550 TI - Problems with rectal foreign bodies. PMID- 4027548 TI - Autoimmunization in testicular torsion. PMID- 4027551 TI - Trypanosomiasis. Introduction. PMID- 4027552 TI - The complement system in sepsis and trauma. PMID- 4027553 TI - Disorders of the carpus in the dog. I. PMID- 4027554 TI - An improved method for the isolation of a neutrophil-rich fraction from porcine blood. PMID- 4027555 TI - The relationship between phagocytosis and intracellular killing of Staphylococcus aureus by bovine neutrophils. PMID- 4027556 TI - Observations on the development in vitro of early (13-day) and later (15-day) porcine embryos. PMID- 4027557 TI - The mating of Libyan fat-tailed ewe lambs. PMID- 4027558 TI - Radioimmunoassay of oestradiol-17 beta in cows' milk after its extraction on Sepharose-coupled antiserum: a study of specificity using high-pressure liquid chromatography. PMID- 4027560 TI - Q-fever control in Cyprus--recent progress. PMID- 4027559 TI - Some aspects of the use of the growth promoter zeranol in ewe lambs retained for breeding. III. Effect on plasma LH levels. PMID- 4027561 TI - Evidence for scanning with unilateral visual presentation of letters. AB - When letters and words are presented tachistoscopically, material from the right visual field (RVF) can be reported more accurately than that from the left visual field (LVF). The RVF superiority may reflect either left hemispheric dominance for language or directional scanning. Previous studies have deliberately focused on the cerebral asymmetry factor while "controlling" scanning and, thus, have cast some doubt on the potency of the scanning factor. Two experiments were conducted to show that scanning can induce a RVF superiority comparable to that often associated with cerebral asymmetry. The first experiment required bilingual subjects to report six English or six Hebrew letters, shown briefly in either the LVF or RVF, with order of report controlled. A RVF superiority found with English characters was matched by an equal but opposite LVF effect with Hebrew. In a second experiment, five English characters were shown briefly in either the LVF or RVF, and subjects had to identify a single character indicated by a post exposural cue. Using a spatial cue to by pass scanning, there were no field differences; with an ordinal position cue--a procedure thought to force scanning- there was a strong RVF superiority. The results show clearly that scanning can induce visual field differences. PMID- 4027562 TI - Reaction times of severe Broca's aphasics to monaural verbal stimuli. AB - Reaction times of nine subjects with severe Broca's aphasia were measured to verbal stimuli presented monaurally to their left or right ears. The aphasic subjects showed left-ear advantages in reaction times to verbal stimuli, paralleling dichotic findings among aphasic patients. The results are interpreted as consistent with right-hemisphere language processing. PMID- 4027563 TI - Semantic priming effects for stimuli presented to the right and left visual fields. AB - Studies that have addressed the possibility of hemispheric differences in semantic priming effects have yielded contradictory results. This paper reports the findings of two experiments intended to shed greater light on the issue of hemispheric differences in semantic priming. Experiment 1 used a hemiretinal paradigm and examined manual response latency and response accuracy to four types of word pairs; categorically related, syntactically related, unrelated, and pairs containing a nonword member. Experiment 2 examined the effects of unrecognized, disambiguating flank words on verbal responses to a centrally presented homograph. Experiment 1 yielded no significant visual field differences in magnitude of priming effects when response latency served as the dependent measure, although categorical relatedness facilitated response accuracy for left but not right visual field stimuli. In experiment 2, the disambiguating words had a significant effect on meaning interpretation of the homographs that was independent of visual field of presentation. Taken together, the results of these studies are interpreted as indicating that semantic aspects of linguistic input are automatically processed and can influence the content and latency of subsequent responses, whether presented to the left or right visual field. PMID- 4027564 TI - The word-superiority effect under conditions that approximate reading. AB - Observers detected a briefly flashed target letter embedded in word, pronounceable nonword, and unpronounceable nonword contexts. The word context facilitated perception under both holistic and analytical processing strategies; the facilitative effect was enhanced when processing was analytical. PMID- 4027565 TI - Development of speech and language following bilateral frontal lesions. AB - Language and speech were studied in a young child with perinatally acquired bifrontal lesions. Bilateral frontal pathology seriously interfered with the development of intelligible speech and resulted in a persistent expressive aphasia. Analysis of the neuropsychological profile indicated impairments in intelligence and language comprehension. These deficits, however, were considered secondary to the profound speech programming disorder. The findings indicate that, despite the plasticity of the immature central nervous system, bilateral frontal injury sustained at an early age precludes the development of intelligible speech. Furthermore, structurally intact cortical regions outside the territories of the speech zones fail to mediate normal speech and language development. PMID- 4027566 TI - The role of the right hemisphere in the control of speech prosody in propositional and affective contexts. AB - Sixteen right-handed adult males with localized insult to either the right or left hemisphere and five control subjects without brain damage read aloud target sentences embedded in paragraphs, while intoning their voices in either a declarative, interrogative, happy, or sad mode. Acoustical analysis of the speech wave was performed. Right-anterior (pre-Rolandic) and right-central (pre- and post-Rolandic) brain-damaged patients spoke with less pitch variation and restricted intonational range across emotional and nonemotional domains, while patients with right posterior (post-Rolandic) damage had exaggerated pitch variation and intonational range across both domains. No such deficits were found in patients with left posterior damage, whose prosody was similar to that of normal control subjects. It is suggested that damage to the right hemisphere alone may result in a primary disturbance of speech prosody that may be independent of the disturbances in affect often noted in right-brain-damaged populations. PMID- 4027567 TI - Surface dyslexia: a regression effect? AB - Although the disorder of acquired surface dyslexia is considered as a pathological syndrome in the psycholinguistic and neuropsychological literature, it may also be conceived of as part of a general regression in functioning consequent upon brain damage. Data on some of the identified features of surface dyslexia were obtained from normal children learning to read and adult subjects, in order to examine the hypothesis that the symptoms are similar to the behavior of unskilled readers, suggesting regression as a more parsimonious explanation for the disorder. Attention is also drawn to problems in quantifying its major feature--the "regularity" effect. PMID- 4027568 TI - The discourse of thought-disordered schizophrenic children. AB - The conversations of two thought-disordered schizophrenic children and two age- and sex-matched normal children were studied in three different contexts. Cohesive relations and retrieval categories were analyzed. The thought-disordered schizophrenic and normal children demonstrated divergent patterns of discourse. These patterns closely paralleled those previously reported for adults by S. Rochester and J. R. Martin (1979, Crazy talk: A study of the discourse of schizophrenic speakers, New York: Plenum) for schizophrenic and normal adults, although some discrepancies were also observed. Recommendations for future research are offered. PMID- 4027569 TI - Information processing and speech lateralization in learning-disabled children. AB - The relationship between information processing and speech lateralization was investigated in learning-disabled children. The Kaufman Assessment Battery for Children (K-ABC) assessed simultaneous and successive processing while a dichotic listening paradigm with free recall and directed attention conditions assessed speech lateralization. A three-factor ANOVA design conducted on the dichotic data revealed that normal children demonstrated stronger right ear advantage (REA); whereas learning-disabled showed weaker right ear advantage. Further, lambda analyses conducted on individual subjects revealed that the learning-disabled did not demonstrate the REA, were not biased attenders, and did not get more right ear than left ear items when attention was directed to one ear. Multiple regression analysis was used to predict sequential processing from the dichotic data for both groups. Learning-disabled children demonstrated a substantial deficit in sequential processing as compared to normal children. These results indicate that learning-disabled children may not have adequate cerebral lateralization of receptive speech processes, shift their attention more readily, and are more inadequate in sequential processing that presumably subserves language functioning. Perhaps learning-disabled children have deficiencies of processor capacity of salient areas of the left (language) hemisphere. PMID- 4027570 TI - Effect of hypothyroidism on the size of spines of pyramidal neurons of the cerebral cortex. AB - We have previously shown that hypothyroidism produces a decrease in the number of spines counted along the apical shafts of pyramidal neurons of the cortex. Nevertheless, other authors have found that when an animal is subjected to some adverse living conditions the size of the spines decreases, making them invisible to the light microscope. The question arises then of whether the decrease in the number of spines reported by us in hypothyroid animals is real or is due to a shrinking effect. In order to elucidate this question the cross-surface area of dendritic spines of apical shafts belonging to 20- and 60-day-old rats, thyroidectomized at 10 days of age, as well as those of their corresponding controls were measured in different layers of their cortex, studied using conventional electron microscopic techniques. The application of the three-way analysis of variance model to these data has shown us that while the age of the animal produces a definite increase in the size of the spines, hypothyroidism does not produce any change in their size, leading us to the conclusion that the decrease in the number of spines previously reported is due to an actual loss of these elements. PMID- 4027571 TI - Lesions of the tissue surrounding the preoptic recess (AV3V region) affect neurosecretory cells in the paraventricular nuclei in the rat. AB - Lesions of the tissue surrounding the preoptic recess (AV3V region) have severe effects on body fluid homeostasis; these include acute adipsia and failure of the antidiuretic response. Because neurosecretory cells in supraoptic nuclei comprise the major source of antidiuretic hormone (ADH) in this species, we have previously observed the fine structure of supraoptic nuclei in rats with AV3V lesions. Paraventricular nuclei are the other major source of ADH in rats. Therefore, in this investigation we compared the fine structure of paraventricular nuclei in rats which had received AV3V lesions 3 days earlier with that of control rats which had received sham lesions and either had drinking water available or had water withheld for 3 days. Degenerating axons and axon terminals were present in paraventricular nuclei of lesioned rats. The degenerating terminals were in axodendritic and less often in axosomatic synapses. Morphometric evaluation revealed that neurosecretory cells did respond to the dehydrated state of the adipsic-lesioned animals, but the response was significantly attenuated compared to that which occurred in sham-lesioned rats deprived of water for 3 days. It appears that AV3V lesions damage afferent connections and impair the response of neurosecretory cells to dehydration in paraventricular as well as supraoptic nuclei. However, in paraventricular nuclei the response is not completely prevented by AV3V lesions during the adipsic period as was observed in supraoptic nuclei. The presence of a response in paraventricular nuclei may be at least partially stimulated by reduced body fluid volume. Information from volume receptors would be carried from the medulla to paraventricular nuclei by ascending pathways which are not affected by AV3V lesions. PMID- 4027572 TI - Interaction of vasopressin with the nigro-striatal dopamine system: site and mechanism of action. AB - The results of the present experiments show that local microinjections of Arg8 vasopressin into the nucl. caudatus cause an increase in the alpha-methyl-p tyrosine methylester-HCl-induced disappearance of dopamine (DA) at the site of administration of the peptide. It is suggested that the caudate nucleus is the site of action of the peptide with respect to its effect on nigrostriatal DA neurons. This conclusion is corroborated by both the finding that microinjection of Arg8-vasopressin into the A9 region, which contains the cell bodies of the nigrostriatal system, was ineffective, and the results of push-pull experiments which showed an enhancement in apparent DA release in the nucl. caudatus when Arg8-vasopressin was co-perfused through the cannula system. Arg8-vasopressin appears to have a rather modest effect on nucl. caudatus DA synthesis, as was deduced from the results of experiments in which the in vitro conversion of tritiated tyrosine into tritiated DA was measured following in vivo Arg8 vasopressin administration as well as after in vitro incubation with the peptide. In conclusion, the interaction of vasopressin with the nigrostriatal DA system appears to be at the level of the DA terminals in the nucl. caudatus rather than at the level of the substantia nigra, and secondly, Arg8-vasopressin appears to affect DA release in the nucl. caudatus rather than DA synthesis. PMID- 4027573 TI - Regional distribution of catecholaminergic terminals in the pigeon visual system. AB - A glyoxilic acid histofluorescence technique was used in this study to determine the distribution of catecholaminergic (CA) terminals in the pigeon visual areas. Our results show that the main visual structures are under the influence of CA nuclei of the brain stem. In particular, the pigeon Wulst, like the mammalian visual cortex, is profusely innervated by CA terminals. In fact, dense CA afferents, most likely noradrenergic (NA) terminals, were found in the hyperstriatum intercalatus superior and the nucleus intercalatus hyperstriati accessorii; area which represent the terminal zone of the retino-thalamo hyperstriatal pathway. These results suggest a possible convergence of NA terminals and visual fibers on common target cells in the Wulst. PMID- 4027574 TI - Single unit activity in lateral reticular nucleus during cortically evoked masticatory movements in rabbits. AB - The activity pattern of the lateral reticular nucleus (LRN) neurones was analyzed during cortically evoked masticatory movements in anesthetized rabbits. Antidromic activation from the cerebellum and histological reconstruction of recorded neurones location from electrode tracks and microdrive readings were the criteria for neuronal identification. Tonic changes as well as rhythmic modulation of neuronal activity were found in a subpopulation of LRN cells during mastication. The same results were observed also in curarized rabbits during fictive mastication. These data support the view that LRN neurones are involved in a central mechanism controlling the masticatory movements. PMID- 4027575 TI - Structural evidence for the neurotoxicity of methylamphetamine in the frontal cortex of gerbils (Meriones unguiculatus): a light and electron microscopical study. AB - Morphological alterations in the CNS were investigated in young gerbils treated with two injections of methylamphetamine (Meth) 8 h apart and killed 3, 5 and 7 days after treatment. In gerbils treated with 2 X 35 mg/kg or higher doses of Meth and prepared according to the terminal degeneration method of Gallyas et al. (Stain Technol., 55 (1980) 299-306), silver precipitates occurred in lamina II and III of the frontal cortex. Electron microscopical studies showed degenerated terminals and neurons. After 3 days of survival we found affected but not degenerating pyramidal cells in the same area. Light microscopical observations after 5 and 7 days of survival indicate a recovery of these cells. All described morphological alterations could be suppressed when Meth was administered in combination with haloperidol. These data and the comparison of aminergic projections to the cortex are discussed on the basis of evidence that Meth induces alteration of mesocortical dopamine nerve fibers and their postsynaptic structures in the frontal cortex (FC). Present results indicate that morphological alterations in young gerbils after Meth treatment are limited to the FC. This is in contrast to the literature, which describes neurotoxic effects of Meth in the neostriatum of various adult mammalian species. PMID- 4027576 TI - Perinodal astrocytic processes at nodes of Ranvier in developing normal and glial cell deficient rat spinal cord. AB - This study examined, during normal development and during the development of a glial cell deficient axon population, the nature of astrocyte involvement at the central nodes of Ranvier on spinal cord axons. One condition examined was the ventral funiculus of normal 7-day-old rats. At this age, the lumbar spinal cord underwent an active phase of gliogenesis, and axons were seen in various stages of myelination. Perinodal astrocytic processes were routinely observed at nodes of axons on which myelin sheaths exceeded 8 compact lamellae. Perinodal astrocytic processes were also seen in close proximity to axolemma at most developing nodes. This study also examined the lumbar spinal cords of rats which were X-irradiated on the third postnatal day. This procedure caused a profound reduction in the astrocyte and oligodendrocyte population in 13- and 18-day-old rats, while sparing the neuronal elements. Thus, axo-glial relationships observed in this tissue are unlikely to be random occurrences. Despite the reduction in glial cells, some oligodendrocyte-myelinated axons were observed in the irradiated spinal cords. Perinodal astrocytes were seen at all oligodendrocyte derived nodes observed in the irradiated cord and appeared to have a specific relationship to the node of Ranvier. The presence of astrocytic processes at the normal, developing node and at the nodes in glial cell deficient spinal cords suggests that astrocytes may be necessary to the function of nodal axolemma. In irradiated spinal cords, where the glial cells are markedly reduced, apposition between astrocytic and oligodendrocytic membrane at the paranode and internode was also seen and was so common that it is highly unlikely to be due to random occurrences. These observations further suggest that in addition to the presumptive role at the nodes, astrocytes may play an inductive or supportive role in the development and maintenance of central myelin. PMID- 4027577 TI - Olfactory discrimination learning is blocked by leupeptin, a thiol protease inhibitor. AB - Rats were trained on successive two-odor discriminations with the cues randomly located in an 8-arm radial maze. After several days of training using different odor pairs, the thiol protease inhibitor leupeptin was infused into the ventricles and testing continued. Leupeptin caused a pronounced, dose-dependent and reversible deficit in performance in this task. Previous studies have shown that these drug concentrations do not influence spontaneous activity, feeding and drinking, or the acquisition and retention of avoidance conditioning. The results are interpreted as supporting the hypothesis that a calcium-sensitive proteinase is involved in certain forms of memory that require modification of telencephalic circuitries. PMID- 4027578 TI - Grasping in the pigeon: mechanisms of motor control. AB - A quantitative analysis of grasping in the pigeon suggests important functional similarities between the visuomotor controls of the avian beak and the primate hand. Beak-opening (gape) during eating is directly proportional to target size and the adjustment is completed prior to contact. The control of gape size involves variations in both the velocity and duration of jaw opening and these parameters are mediated by different effector systems (jaw muscles, neck muscles). Nerve section experiments were used to identify jaw motoneurons which are components of the final common path for grasping. Grasping in the pigeon approximates the functional complexity of mammalian visuomotor behavior but is mediated by a relatively simple effector system. PMID- 4027579 TI - Crossing dendrites may be a substrate for synchronized activation of penile motoneurons. AB - The morphology of perineal and extensor hindlimb motoneurons in adult male rats was examined using retrograde labelling with wheat germ agglutinin and horseradish peroxidase. Bulbocavernosus and levator ani motoneurons, located in the spinal nucleus of the bulbocavernosus, were organized as distinct clusters of motoneurons in the medial ventral area of the lumbar (L6-L5) spinal cord and possessed prominent contralaterally projecting dendritic arborizations. In similar experiments, laterally located soleus and extensor digitorum longus motoneurons did not exhibit a similar organization. These findings are discussed with respect to their possible role in the synchronized bilateral activation of penile muscles. PMID- 4027580 TI - Retinal origin of the fasciculus medialis tractus optici in adult goldfish. AB - In teleosts, the fasciculus medialis tractus optici departs the optic tract and follows an aberrant path towards the midbrain tectum. To determine the retinal origin of the fascicle, horseradish peroxidase was injected into localized lesions of either the optic nerve or the retina. The fasciculus medialis axons of adult goldfish derive selectively from ganglion cells residing in the dorsotemporal portion of the central retina. The fasciculus medialis appears to be an integral part of the chronotopic ordering of fibers in the optic tract. PMID- 4027581 TI - Reduced dipsogenic responsiveness to intracerebroventricularly administered angiotensin II in estrogen-treated rats. AB - Chronic administration of two doses of estradiol benzoate (30 and 46 micrograms/kg/day) reduced the drinking response to acute administration of either isoproterenol (25 micrograms/kg, s.c.), the beta-adrenergic agonist, or angiotensin II (Ang II) (200 micrograms/kg, s.c.). The drinking response to intracerebroventricular administration of Ang II (40 ng/kg), but not carbachol (800 ng/kg), was also attenuated in estrogen-treated rats. An assessment of the Ang II binding in a diencephalic block of tissue from estrogen-treated rats revealed a significant reduction compared to untreated controls. The results suggest, but do not prove, that the reduced drinking response observed in estrogen-treated rats may be related to a reduction in the number of Ang II receptors in the brain. PMID- 4027582 TI - Splenic, renal, and cardiac nerves have unequal dependence upon tonic supraspinal inputs. AB - Stimulation of visceral receptors can lead to unequal reflex responses in splenic, renal and cardiac sympathetic nerves. Activity of splenic nerves is often more excited or less inhibited than that of cardiac or renal nerves. This study was undertaken to determine potential differences in resting discharge among these 3 nerves. Dependence upon supraspinal drive was evaluated by comparing the relative decrease in activity of these nerves in chloralose anesthetized cats 30 min to 2 h following high cervical spinal cord transection. After this transection, discharge rates of cardiac and renal nerves were significantly depressed to less than 50% of initial values. In contrast, splenic nerve activity was not significantly affected. To determine if this sustained splenic nerve activity resulted from greater responsiveness to potential external sources of excitation, splenic, renal and cardiac neural responses to factors known to affect sympathetic discharge in spinal animals were compared. Neither increased arterial pressure, decreased arterial pressure, systemic hypercapnia and acidosis, nor thoracolumbar dorsal rhizotomy revealed specific inputs responsible for the preferential maintenance of splenic nerve activity in spinal cats. It was concluded that ongoing activity of splenic nerves is less dependent upon supraspinal sources of excitation than is activity of renal or cardiac nerves. The cause of this difference among these 3 components of sympathetic outflow remains to be determined. PMID- 4027583 TI - Long-term effects of superior cervical ganglionectomy on cortical blood flow of non-anesthetized rabbits in resting and hypertensive conditions. AB - The long-term effects of sympathectomy on cerebral cortical blood flow (CBF) were studied in the conscious rabbit. The quantitative, repeated measurements of blood flow were made by determination of helium clearance by mass spectrometry and were obtained simultaneously with measurements of local tissue pO2 and pCO2. Eight to 10 weeks after unilateral sympathectomy, resting blood flow in the homolateral cortex was decreased by a mean of 17% compared to the heterolateral cortex. In two animals in which blood flow was recorded both before and after the sympathectomy, the same phenomenon was observed from 8 to 30 days after the operation. The response to i.v. infusion of noradrenaline was identical in both hemispheres: doses inducing a 40% rise in blood pressure did not significantly modify CBF. The responses to angiotensin II-induced hypertension were also identical. Histochemical verifications demonstrated the effectiveness of the denervation in the pial arteries and the intraparenchymal arteries in the region studied. Thus the decrease in CBF induced by chronic sympathectomy cannot be attributed to the development of hypersensitivity to catecholamines. This decrease remained stable whatever the value of resting flow and was maintained under anesthesia. It is concluded that, as in the peripheral circulation, chronic sympathectomy affects the equilibrium of the vascular smooth muscle fibers, but that circulating amines play no compensatory role in the cerebral circulation because of the blood-brain barrier. PMID- 4027584 TI - Neurotensin depolarizes substantia nigra dopamine neurones. AB - Neurotensin and the C-terminal 8-13 amino acid fragment were found to excite substantia nigra compacta dopamine neurones in vitro in a dose-dependent manner. The N-terminal 1-8 amino acid fragment was not active at the concentrations used. Desensitization was not observed. Intracellular recordings from the neurones responding to dopamine showed neurotensin-depolarized cells with an increase or no change in input resistance. These actions persisted in zero calcium, 8 mM magnesium artificial CSF suggesting a post-synaptic action. PMID- 4027585 TI - Increased brain norepinephrine metabolism correlated with analgesia produced by the periaqueductal gray injection of opiates. AB - Dose-dependent increases in 3-methoxy-4-hydroxyphenylethyleneglycol sulfate (MOPEG-SO4), a major metabolite of norepinephrine, were produced in the limbic forebrain and cerebral cortex 30 min after the bilateral injection of morphine into the periaqueductal gray (PAG). These effects were also elicited by similar injections of levorphanol. Highly significant correlations were obtained between the concentrations of MOPEG-SO4 and the analgesic effect of the opiates and opiate actions were antagonized by systemic naloxone. These results indicate that activation of opiate receptors in the PAG may elicit the involvement of noradrenergic systems in distant brain regions in the mediation of analgesia. PMID- 4027586 TI - Effect of blood pressure on A2 noradrenergic neurons. AB - Single-unit recordings of A2 noradrenergic neurons were obtained in urethane anesthetized rats. Norepinephrine-induced elevations in arterial pressure produced small decreases in the discharge rate of the cells; this effect was not observed in animals with bilateral sections of the ninth and tenth nerves. The activity of A2 cells was neither pulse-synchronous at high levels of arterial pressure nor significantly affected by carotid stretch. It is concluded that these neurons do not receive a significant baroreceptor input. PMID- 4027587 TI - Chromophores in the extraretinal photoreceptor (pineal organ) of teleosts. AB - We have demonstrated, using a highly sensitive high performance liquid chromatography technique, that the pineal organ (epiphysis cerebri) of the rainbow trout contains both 11-cis-retinal and 11-cis-3-dehydroretinal. These compounds were assumed to be the chromophores of pineal photopigments, because they were isomerized to all-trans forms by light-adaptation. The quantity of chromophores in the dark-adapted pineal organ was extremely low (9.2-29.1 pmol/pineal), corresponding to approximately 1/300-1/1000 of that of the retina. PMID- 4027588 TI - Intracellular potentials of salamander mitral/tufted neurons in response to odor stimulation. AB - Intracellular responses of salamander mitral/tufted neurons to defined odor pulses are described. Responses to odor stimulation, which generally are more complex than responses to olfactory nerve or tract electrical stimulation, show periods of depolarization and hyperpolarization that are influenced by odor concentration and quality. The way these periods coincide with different types of spike patterns in individual cells supports the hypothesis that the temporal patterning of odor responses is generated by differential activation of bulbar circuits. PMID- 4027589 TI - Electrical stimulation of mesencephalic cell groups (A9-A10) produces monosynaptic excitatory potentials in rat frontal cortex. AB - Electrical stimulation of the ventral tegmental area and substantia nigra produces monosynaptic and polysynaptic excitatory postsynaptic potentials in rat frontal neurons that can be recorded intracellularly. The electrophysiological characteristics of the monosynaptic responses and the possibility that dopamine (DA) mediates these events are discussed. PMID- 4027590 TI - Effects of ganglioside treatment in rats with a lesion of the cholinergic forebrain nuclei. AB - The effects of GM1 ganglioside (30 mg/kg i.p.) administration for 22 days on choline acetyltransferase (ChAT) activity and noradrenaline (NA) levels in the cerebral cortex and on the acquisition of active and passive avoidance conditioned responses were investigated in both sham-operated rats and in rats with a unilateral electrolytic lesion of the magnocellular forebrain nuclei (MFN). A statistically significant ChAT decrease in cortical areas ipsilateral to the lesion was found in saline-treated lesioned rats. In the lesioned GM1-treated rats, ChAT activity was only reduced in the frontoparietal areas and was significantly increased in the ipsilateral parietooccipital areas as well as in both contralateral regions. NA levels in the cortex were neither significantly affected by the lesion nor by GM1 treatment. The lesion impaired the acquisition of active and passive conditioned avoidance responses. GM1 treatment improved acquisition of the active avoidance response in the lesioned rats as indicated by a larger number of avoidances and a smaller number of escape failures during training in comparison with saline treatment. Ganglioside had no effect on the passive avoidance responses. These results demonstrate that GM1 administration facilitates the recovery of the cortical cholinergic system and of behavioral responses impaired by an electrolytic lesion of the cholinergic forebrain nuclei. PMID- 4027591 TI - Free and conjugated amino acids in human CSF: influence of age and sex. AB - An extended baseline characterization of amino acids (AAs) and related amino compounds in CSF is reported. Thirty-one amino compounds were measured in deproteinized CSF before and after acid hydrolysis using a triple-column HPLC/fluorometric analyzer. CSF specimens were collected under strictly controlled conditions from neurologically normal myelogram patients and carefully pooled with regard to subject age and sex. Consideration was given to factors which may produce artifactual alterations in AA levels during CSF collection, storage and handling. Conjugated AAs were determined as the difference between levels of free AAs (measured in CSF prior to hydrolysis) and total AAs (measured in hydrolyzed CSF) and are taken as an index of total CSF peptide AAs. Results documented conjugated forms of all non-acid-labile CSF AAs except citrulline and ethanolamine. In general, ratios of conjugated to free AAs were relatively low, however for the neurotransmitter AAs aspartate, glutamate, glycine and GABA as well as for beta-alanine hydrolysis produced marked increases indicating that these compounds are present predominantly in bound form in CSF. Results also revealed the significant influence of both age and sex on levels of a number of CSF free and conjugated AAs. Compared to younger individuals (those less than 40 years of age), older individuals exhibited significantly higher levels of free aspartate, glycine, alpha-aminobutyric acid, valine, isoleucine, leucine, phenylalanine and 3-methylhistidine as well as significantly lower levels of free phosphoethanolamine, serine, GABA, homocarnosine, conjugated GABA and conjugated beta-alanine. Additionally, significantly higher levels of free tyrosine, ethanolamine, arginine and conjugated aspartate were documented in males compared to females.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4027593 TI - Abnormal Y/X ratio in the area centralis of the Siamese cat. AB - The responses of X- and Y-type retinal ganglion cells were recorded in the optic tract of Siamese cats in order to investigate the encounter rate of Y-cells with respect to retinal eccentricity. The percentage of Y-cells in Siamese cats was highest in or near the area centralis and it decreased with eccentricity. This is in contrast to the proportion of Y-cells in normally pigmented cats, which was lowest in the area centralis and increased with eccentricity. Thus, the Y/X ratio in Siamese cats is higher in the area centralis, but significantly lower in the peripheral retina compared to those in normal controls. The lower percentage of Y cells in the periphery parallels an additional finding that Y-cells exhibiting very high conduction velocities were missing from the Siamese cat optic tract. Finally, the receptive-field center (RFC) size of X-cells in the area centralis was larger in Siamese cats, and the correlation between the RFC size and conduction velocity was weak in these animals. The results are discussed in terms of behavioral deficits in Siamese cat vision. PMID- 4027592 TI - Regional distribution of a novel pituitary protein (7B2) in the rat brain. AB - The regional distribution of a novel pituitary protein (7B2) in the rat brain was studied using a specific and sensitive radioimmunoassay. Immunoreactive (IR)-7B2 was distributed throughout the brain, with the highest concentrations in the pituitary, hypothalamus and basal ganglia. Immunoreactive 7B2 from the brain and other tissues had an apparent molecular weight of around 20,000 as estimated by SDS-polyacrylamide gel electrophoresis as observed with other tissues. In homozygous Brattleboro rats which do not synthesize vasopressin or its associated neurophysin, IR-7B2 levels in the brain and pituitary gland were shown to be similar to those of control animals. Furthermore, the molecular weight of 7B2 in the brain and pituitary gland of homozygous Brattleboro rats was similar to that of control animals. PMID- 4027594 TI - Profound disturbances of spontaneous and learned behaviors following lesions of the nucleus basalis magnocellularis in the rat. AB - It has been shown that a marked decline in the cortical activity of the cholinergic synthesizing enzyme choline-acetyltransferase (ChAT), accompanied by a severe neuronal loss in the nucleus basalis magnocellularis of Meynert occurs in the brains of patients with senile dementia of the Alzheimer type. However, the functional role of these neurons is largely unknown. In fact, very few studies have been done in animals. In this paper we report the behavioral effects of the lesion of the nucleus basalis magnocellularis in the rat either by radiofrequency current or by ibotenic acid injection at the level of the cell bodies. The two kinds of lesion lead to a profound disturbance of spontaneous and learned behaviors. There is a complete disorganization of behavior which is evidenced by an enhanced locomotor activity, an alteration in alimentary and hoarding behavior. In addition, we observed a deterioration of spatial memory and an incapacity to reverse a previously learned response. Biochemical assay showed that radiofrequency and ibotenic acid lesions produced a decrease of ChAT activity in the prefrontal and sensorimotor cortices and in amygdala without affecting the hippocampus or striatum. Ibotenic acid lesions seem to specifically destroy the cell bodies of the nucleus basalis magnocellularis since the dopaminergic and noradrenergic fibers of passage remained intact as measured by the unchanged level of endogenous catecholamine concentration in the terminal region in the prefrontal cortex. Presently, it cannot be said that the behavioral syndrome results solely from the lesion of the cholinergic neurons. Also, it is likely that the lesion of the nucleus basalis magnocellularis in the rat does not exactly reproduce the behavioral syndrome observed in Alzheimer's disease in man. However, this experimental approach in leading to a better knowledge of the functioning of these neurones could improve our understanding of this disease. PMID- 4027595 TI - Influence of olfactory bulb on dendritic knob density of rat olfactory receptor neurons in vitro. AB - The maturation of olfactory receptor cells is facilitated by the presence of their target tissue, the olfactory bulb. Organ cultures of embryonic rat olfactory mucosa (OM) maintained in the presence of the presumptive olfactory bulb (POB) had a significantly higher (1.6 X) density of ciliated dendritic knobs than those without the POB. No significant difference was found in the density of non-ciliated dendritic knobs and total knob density in these two groups of cultures. A control group of explants in which the OM and POB had been separated and recombined also showed an increased ciliated dendritic knob density. The area of the olfactory epithelium was the same whether or not the POB was present. In addition, scanning electron microscopy observations revealed a high degree of heterogeneity in the surface morphology of the olfactory epithelium. PMID- 4027596 TI - Cortical acetylcholine efflux with hypercapnia and nociceptive stimulation. AB - In rabbits anesthetized with 70% N2O-30% O2, the rate of efflux of acetylcholine (ACh) from the cerebral cortex doubled during hypercapnia (increase of end-tidal CO2 from 4 to 8%), and during mild nociceptive stimulation of the tail. Under 0.7% halothane anesthesia, the control rate of ACh efflux was lower than that under N2O; the rate rose 2-fold during hypercapnia and 4-fold during tail stimulation. In the absence of systemic atropinization, increase in ACh efflux was correlated with a shift in EEG from high- to low-voltage ('activated'); after systemic atropinization EEG remained in the high-voltage state, but the changes in ACh efflux with hypercapnia and stimulation were not affected. Following transection of the midbrain, ACh efflux was markedly depressed and did not change during hypercapnia. Taken in context with the previously known facts that the cerebral hyperemia of hypercapnia is potentiated by cholinesterase inhibition and attenuated by atropine or decerebration, the present results support the concept of a cholinergic regulation of the cerebral vasculature. PMID- 4027597 TI - Voltage- and current-clamp recordings of the receptor potential in olfactory receptor cells in situ. AB - Intracellular recordings obtained using the whole cell configuration of the patch recording technique show that isolated somas of olfactory receptor cells are electrogenic, producing fast overshooting action potentials when depolarized. In situ, these cells produce graded receptor potentials and action potentials when stimulated chemically. The receptor potential can be voltage clamped for analysis of the ionic basis of sensory transduction in olfaction. PMID- 4027598 TI - Kainic acid-induced seizures: dose-relationship of behavioural, neurochemical and histopathological changes. AB - Behavioural, neurochemical and histopathological changes induced by systemic injection of kainic acid were investigated at various doses of the neurotoxin (3, 6 and 10 mg/kg s.c.). There was a positive correlation between the dose of kainic acid and the extent of both the acute neurochemical changes 3 h after the injection (increases of 3,4-dihydroxyphenylacetic acid and 5-hydroxyindoleacetic acid levels and a decrease in noradrenaline levels in all brain regions investigated), the acute histopathological changes (shrinkage and condensation of nerve cells and brain oedema in the entire forebrain) and the extent of behavioural alterations (immobility, 'wet dog shakes' and limbic seizures). However, the slope of the dose-response curves was very steep. Late and irreversible alterations included losses of the enzyme markers glutamic acid decarboxylase and choline acetyltransferase and, histopathologically, incomplete parenchymal necrosis and haemorrhages. These changes, however, were restricted to a few brain regions, the most important being the hippocampus, amygdala, entorhinal and pyriform cortex, and olfactory bulb, and they were seen only in animals which had undergone severe convulsions. It is suggested that the irreversible brain lesions in this animal model of limbic (temporal lobe) epilepsy are not solely induced by a direct action of kainic acid, but may be caused--at least in part--by additional, secondary pathogenetic mechanisms. PMID- 4027599 TI - Hypertrophy of cholinergic neurones of the rat basal nucleus following section of the corpus callosum. AB - The effect of division of the corpus callosum on immunohistochemically identified cholinergic neurones of the basal nucleus has been examined in rats. Following callosal section the cholinergic cell bodies on both sides are significantly larger (25%) than those in normal animals. This hypertrophy persists for at least 62 days after operation, the longest survival time examined. It is greatest when the animal is operated on in infancy, but it occurs at all ages examined. The enlargement is similar to that seen in the cells of the same nucleus on one side following contralateral cortical damage. PMID- 4027600 TI - Retinal and tectal responses to alternating gratings are unaffected by monocular deprivation in pigeons. AB - Retinal and tectal potentials to alternating gratings were recorded in pigeons raised monocularly deprived. Deprived eyes showed consistent myopia and anterior posterior axis elongation. In addition, vitreal opacities were observed in 70% of the deprived eyes. In pigeons with vitreal opacities, a reduction of retinal and tectal response amplitude was consistently found in the high spatial frequency range. Pigeons with clear media of the deprived eyes showed normal retinal and tectal responses. PMID- 4027601 TI - Effects of intrahypothalamic kainic acid injection on taurine levels, binding and uptake. AB - The neurochemical effects of unilateral intrahypothalamic injection of kainic acid on taurine levels and synaptosomal uptake and binding of taurine were investigated. Seven days after the kainic acid injections, there were no changes in either taurine uptake or binding. However, taurine levels were significantly increased by 54% over the control contralateral side. These data are consistent with the hypothesis that taurine is localized in glial cells; the increased levels being a result of gliosis after kainic acid injections. PMID- 4027602 TI - Electrophysiological evidence for the presence of fibers in continuity between dorsal and ventral roots in the cat. AB - Action potentials were recorded from the L7 or S1 dorsal root of the cat following stimulation of the peripheral end of the cut ventral root of the same segment. Conversely, action potentials were also recorded from the ventral root while stimulating the peripheral end of the cut dorsal root. Based on the conduction velocities of 52 single fibers, one-third were A delta-fibers and the remaining two-thirds belonged to the C-fiber category. These results suggest that there are both A- and C-fibers in continuity between the dorsal and the ventral root. PMID- 4027603 TI - The descending alpha-MSHergic (alpha-melanocyte-stimulating hormone-ergic) projections from the zona incerta and lateral hypothalamic area to the inferior colliculus and spinal cord in the rat. AB - Neuronal pathways containing alpha-melanocyte-stimulating hormone (alpha-MSH) extending from the zona incerta and lateral hypothalamic area to the inferior colliculus and spinal cord were analyzed using both immunohistochemical localization and a retrograde tracer. Biotinized horseradish peroxidase injected into the inferior colliculus or the thoracic cord of the rat labeled a number of neurons in the zona incerta and lateral hypothalamic area. Simultaneous immunostaining of the same sections with alpha-MSH antiserum showed that some of these neurons are alpha-MSHergic. PMID- 4027604 TI - In vitro dopamine biosynthesis in the median eminence of rat hypothalamic slices: possible involvement of a Na+-Ca2+ exchange mechanism. AB - Equimolar replacement of Na+ in medium with choline chloride or sucrose and experimental manipulations known to increase [Na+]i, such as ouabain addition and K+ deprivation from medium, caused a marked increase in in vitro DOPA synthesis in the median eminence of rat hypothalamic slices in a Ca2+-dependent manner. These results suggest that a Na+-Ca2+ exchange mechanism is closely involved in the regulation of dopamine biosynthesis in tuberoinfundibular neurons. PMID- 4027605 TI - Tonotopic organization in the midbrain of a teleost fish. AB - Recordings from small clusters of units within the auditory midbrain of the Japanese carp, Cyprinus carpio, provide the first evidence for tonotopy within the teleost brain. These findings suggest that place mechanisms of frequency coding and tonotopy, previously thought to have evolved first in amphibians, may be general and ancient features of the vertebrate auditory system. PMID- 4027606 TI - Responses of pulvinar neurons to real and self-induced stimulus movement. AB - Many neurons in the pulvinar nuclei of awake monkeys respond to real image motion while the animal maintains fixation. Many of these same cells do not discharge to comparable stimulus movement when it is caused by an eye movement. This lack of sensory response is most likely mediated by an extraretinal signal. PMID- 4027607 TI - Receptive field size of hair follicle afferents in rats treated neonatally with capsaicin. AB - Receptive field parameters of G- and D-hair units were investigated in adult rats given capsaicin as neonates. An air jet stimulator mounted on a two-way micromanipulator was used for accurate mapping of receptive fields. Diameters of G- and D-hair unit receptive fields were similar in both control and treated groups averaging 2.14 and 2.44 mm respectively with a 1.5 X threshold stimulus. It is concluded that the reported expansion of rat spinal cord cutaneous receptive fields following capsaicin treatment does not have any significant peripheral component. PMID- 4027608 TI - Inhibition of nociceptive evoked activity in spinal neurons through a dorsal column-brainstem-spinal loop. AB - In decerebrate-decerebellate cats, dorsal column stimulation (DCst), rostral to bilateral dorsal column cuts, inhibited dorsal horn neurons discharging to various types of nociceptive stimuli. Similar inhibitory effects were observed from conditioning nucleus raphe magnus stimulation. Activation of this dorsal column-brainstem-spinal loop could be part of an important supraspinal "gating' system to account for the alleviation of pain both by DCst and peripheral nerve stimulation in man. PMID- 4027609 TI - Sympathetic activation of unmyelinated mechanoreceptors in cat skin. AB - In single unit recordings from the saphenous nerve in anesthetized cats, afferent units were functionally identified as unmyelinated (C) mechanoreceptors. All units responded to stimulation of the sympathetic trunk with a repetitive discharge which was maintained throughout the period of stimulation. This discharge was asynchronous with respect to efferent activity and was unaffected by brief occlusion of the arterial blood supply. The mechanism underlying the strong excitatory action of the sympathetic system on these afferents is not known although changes in blood flow and temperature can be ruled out. It is suggested that the primary function of these afferents may be to signal conditions within the skin for regulatory purposes rather than to encode external mechanical events. PMID- 4027610 TI - Terminations of primary afferents on lumbar motoneurons in the turtle Pseudemys scripta elegans. AB - The existence of monosynaptic contacts between primary afferents and motoneurons in the lumbar spinal cord of the turtle Pseudemys scripta elegans was demonstrated by intracellular injections of horseradish peroxidase. Three afferent-motoneuron combinations were satisfactorily labeled and revealed 1, 4 and 6 contacts respectively. All contacts were made on the dorsal dendritic tree of the motoneurons. It is suggested that the contacting primary afferents are from muscle spindles. PMID- 4027611 TI - Sexual dimorphism of pleopod motor neurons in lobster. AB - Sexual dimorphism of the efferent neurons that innervate the pleopods in the first abdominal segment of the lobster was examined with nickel/cobalt backfilling techniques. An average of 28.8 somata (maximum of 31) were stained in the female while the mean number of male efferent somata was 25.8 (maximum of 28). These differences are statistically significant. All except one of these somata are situated close to the base of the ipsilateral first root. They are organized into large anterior (13-21 somata) and small posterior (8-13) clusters. One soma is located on the contralateral side of the ganglion. PMID- 4027613 TI - A comparison of the number of neurons in individual laminae of cortical areas 17, 18 and posteromedial suprasylvian (PMLS) area in the cat. AB - The binocular region of area 17 (17B) has a greater number of neurons under a given unit of cortical surface (NC, number per column) than either the monocular region of area 17 (17M), area 18 or the posteromedial suprasylvian area (PMLS). The latter three areas follow the general principle of basic uniformity in the number of neurons under given units of cortical surface formulated by Rockel et al. This basic uniformity is maintained in layers I and II. The NC of other layers varies. The greatest differences are found in layer IV where the NC of each area is significantly different from that of each other area. Though the difference between layer IV of 17M and of either 18 and PMLS is largely offset by changes in the third layer, layers V (PMLS) and VI (18 and PMLS) also contribute to the compensation. The compensation between 18 and PMLS is due entirely to changes in layer VI. It is important to note that there are statistically demonstrable interindividual differences in the neuronal NC of the cats used in the present study. We suggest that these may be due to age, breeding, or rearing conditions, probably the latter. PMID- 4027612 TI - Down-regulation of neural corticosterone receptors by corticosterone and dexamethasone. AB - Stress or elevated corticosterone titers can reduce the concentration of corticosterone receptors in the brain. We demonstrate that corticosterone and the related glucocorticoid, dexamethasone, induce different anatomical patterns of such 'down-regulation'. Corticosterone administration reduces receptor number in the hippocampus, particularly the CA1 and CA2 pyramidal cell fields, but nowhere else in the brain or pituitary. In contrast, equivalent dosages of dexamethasone down-regulate pituitary, amygdaloid and hypothalamic corticosterone receptor numbers. These different anatomical profiles of sensitivity to down-regulation appear due to differential access of the two steroids to the receptor pools. PMID- 4027614 TI - Determination of excitability in human proprioceptive reflexes: analysis and characteristics of EMG thresholds of postural muscle. AB - In order to derive indirect indices of reflex excitability, human soleus (Sol) H reflex and direct M response threshold intensities (HT, MT) were determined by probit analysis of quantal responses elicited in the surface electromyogram (EMG). Within sessions, HT and MT co-varied with respect to time along a logarithmic time-course, both attaining effectively stable levels after 40-60 min of recording. The pattern of this co-variation was imposed by non-reflex factors, primarily the electrode system employed. Sampling distributions of stable thresholds were positively skewed (median values: HT, 5.20 mA, MT, 6.83 mA), and concurrently determined values were strongly correlated (r = 0.965). The Sol threshold ratio (HT/MT) was largely unaffected by non-reflex factors and was therefore stable within subjects, both within sessions (with respect to time) and between sessions. This ratio was normally distributed (mean = 0.753 +/- 0.079 S.D.). Criteria of indirect indices of reflex excitability are proposed: HT satisfies the criteria applicable to a relative index. However, the characteristics of the threshold ratio permit its use as a powerful absolute index of proprioceptive reflex excitability. PMID- 4027615 TI - Induction of brain tubulin by triiodothyronine: dual effect of the hormone on the synthesis and turnover of the protein. AB - The relative effects of triiodothyronine (T3) on the synthesis and turnover of tubulin in the developing rat and chick brain have been examined. Measurements of rates of turnover of radiolabeled tubulin in the hormone-sensitive tissues show that the half-life of tubulin turnover is 4-6 h in the absence of T3 and 10-12 h in the presence of the hormone. Analysis of short-term kinetic data on the stimulation of tubulin by T3 in the chick brain show that the rapid induction is due to a dual effect of the hormone on the metabolism of tubulin--an increase in the rate of synthesis as well as a decline in its rate of turnover. PMID- 4027616 TI - Intracranial potentials correlated with an event-related potential, P300, in the cat. AB - Intracranial recordings of long-latency, event-related potentials were obtained from paralyzed, artificially respirated cats. A modified oddball paradigm was employed in which cats were presented with a randomized series of two tones, a 'frequent' 4 kHz stimulus and a 'rare' 1 kHz stimulus. A tail shock was administered 700 ms after onset of the rare tone. Under these circumstances the stimulus elicited a positive component at the vertex similar to the human P300. Intracranial potentials associated with the rare tone usually manifested components of greater amplitude than did potentials associated with the frequent tone. A positive component occurring in latency between 200 and 350 ms only accompanied the presentation of the rare stimulus. The P300 component, which was positive at the dura, appeared as a negative component within a few millimeters of the surface over a wide area of the marginal and suprasylvian gyri. Changing the probability of the rare stimulus resulted in a reduction in the amplitudes of both the intracranial negative component and the P300 recorded at the skull. Components of large amplitude associated with the rare stimulus were obtained from the region of the hippocampus. These components reversed polarity, sometimes more than once, as the electrode was advanced. Substantial latency differences were often observed between the P300 recorded at the skull and P300-like intracranial components associated with the rare stimulus. These results suggest that the cortices of the marginal and suprasylvian gyri and the hippocampal region contribute to the generation of the cat P300. PMID- 4027617 TI - High-resolution 2-deoxyglucose autoradiography in quick-frozen slabs of neonatal rat olfactory bulb. AB - We have used rapid freezing and freeze-substitution fixation to permit electron microscopic study of [3H]2-deoxyglucose autoradiographs. The techniques minimize diffusion of label into processing fluids and, by inference, migration of label within tissue. Slabs of olfactory bulbs from 12-day-old rats were quick-frozen after one hour of exposure to physiological olfactory stimuli. In light microscopic autoradiographs at low magnification, the neuropil of individual olfactory glomeruli appeared uniformly labeled with different levels of labeling in different glomeruli. At higher magnification, glomerular neuropil labeling consisted of small unlabeled regions surrounded by label clusters, suggesting greater deoxyglucose uptake by olfactory nerve terminals as compared with their postsynaptic dendrites. Periglomerular neurons were labeled differentially. Some microglia and glia precursor cells were heavily labeled in all bulbar laminae. The ultrastructure of cells and neuropil in all bulbar laminae was well preserved. Cell processes and organelles could be identified in both stained sections and unstained electron microscopic autoradiographs. These experiments demonstrate the feasibility of combining quick-freezing with freeze substitution, in order to extend the resolution of studies using diffusable tracers such as 2 deoxyglucose. The results suggest that this is a promising method for assessing several controversies concerning deoxyglucose incorporation and neuronal and glial metabolism. PMID- 4027618 TI - Antisera to different glycolipids induce myelin alterations in mouse spinal cord tissue cultures. AB - To study the demyelinative effects of antibodies to glycolipids, well-myelinated cultures of mouse spinal cord tissue were exposed to antisera against galactocerebroside and two gangliosides (GM1 and GM4), as well as to anti-white matter antiserum. The demyelinative process was evaluated by morphologic and biochemical techniques. Cultures exposed to anti-white matter and anti galactocerebroside antisera showed the most marked changes. These consisted of a decrease in the number of oligodendroglial cells and dissolution and phagocytosis of myelin. Concomitantly, the activity of 2',3'-cyclic nucleotide-3' phosphohydrolase (CNPase) was decreased by 60-70%. This occurred within 24 h of exposure to a relatively low concentration of serum (10%). Cultures exposed to anti-GM1 and anti-GM4 antisera showed similar changes but to a lesser degree. The CNPase activity was decreased about 30% within 48 h of exposure to a 25% concentration of these antisera. This diminution represents about a 20% loss of myelin, an observation corroborated by electron microscopy where myelin but not oligodendroglial cell loss was observed. Therefore, in addition to anti galactocerebroside activity, which was previously found to be the major antibody responsible for the demyelinating activity induced by anti-whole CNS tissue antiserum, these data suggest that antibodies to gangliosides like GM1 and GM4 might also play a role in immune-mediated demyelination, including perhaps, the human demyelinating diseases. PMID- 4027619 TI - The response of optic tract glia during regeneration of the goldfish visual system. II. Tectal factors stimulate optic tract glia. AB - After transection, retinal ganglion cell axons of the goldfish will regenerate by growing into a primary target tissue, the optic tectum. To determine what role the target tissue may play in regulating glial cell growth, we measured biosynthetic activity of optic tract glia following excision of the optic tectum and compared it to activity of glia found in the regenerating visual system. Ablation of the tectum reduced glial incorporation of both [3H]thymidine and [35S]methionine. Tectal ablation also led to nearly 80% reduction of amino acids incorporated by oligodendroglia as well as a decrease in the amount of newly synthesized protein found within multipotential glia and within cytoplasmic projections of astroglia. Since the tectal influence upon optic tract glia was detected at a time when tract and tectum are physically separated, we sought to determine if the optic tectum contained soluble glia-promoting factors. A soluble fraction recovered from tecta of the regenerating visual system increased amino acid incorporation within optic tract glia at 2-3-fold above preparations incubated with fractions from control, intact tecta. Comparisons of radiolabeled proteins separated by sodium dodecyl polyacrylamide gel electrophoresis from regenerating and factor-stimulated optic tract were similar and indicated that a soluble tectal fraction promoted biosynthesis of specific glial proteins. Our findings suggest that during regeneration of the goldfish visual system glia are influenced by humoral factor(s) released from the synaptic target site. PMID- 4027620 TI - Effects of neonatal treatment with monosodium glutamate on circadian locomotor rhythm in the rat. AB - In order to study the effects of treatment with monosodium glutamate (MSG) during the neonatal period on the intrinsic circadian timekeeping system in rats, the locomotor activity of blinded MSG-treated and control (saline-treated) rats was analyzed with power spectral analysis and cross-correlation. In contrast to a robust free-running circadian rhythm in the control rats, a significant shortening of the circadian period and rapid decomposition into ultradian components were noted in the MSG-treated rats. Computer-assisted stereometry of the hypothalamic nuclei revealed that, in addition to the well-known severe damage in the arcuate nuclei (ARC), the volumes of the suprachiasmatic nuclei (SCN) and ventromedial hypothalamic nuclei (VMH) were also reduced significantly in the MSG-treated rats. Although no gross histological damage was apparent in either the SCN and VMH, neonatal MSG treatment appears to impair the function of SCN to integrate many minor oscillations in the brain into a single, definite and precise circadian period. PMID- 4027621 TI - Effect of reduction of cholinergic input on the concentration of specific proteins in different cortical regions of the rat brain. AB - The effect of lesioning the nucleus of the tractus diagonalis on the concentration of specific proteins in the hippocampus and the occipital cortex was assessed. Rats received either a sham or an electrolytic lesion and were killed 9 or 35 days later. Tissue samples were removed by microdissection and proteins were separated by two-dimensional gel electrophoresis. Gels were stained with silver, and then analyzed by quantitative computerized scanning densitometry. Of the 143 proteins analyzed, only four were found to be altered in concentration in both brain areas as a result of the lesion. Protein 82 (molecular weight 39,000, pI 6.5) was reduced 71% in the hippocampus and 50% in the occipital cortex 9 days after the lesion, while protein 109 (molecular weight 32,000, pI 6.4) was elevated 140% in the hippocampus and 130% in the occipital cortex at the same time point. Protein 6 (molecular weight 58,000, pI 5.7) was unchanged 9 days after the lesion but was elevated in concentration in both the hippocampus and the occipital cortex 35 days after lesioning. Protein 74 (molecular weight 39,000, pI 5.8) was elevated in concentration both 9 and 35 days after lesioning in the occipital cortex, but only at day 35 in the hippocampus. These results demonstrate that the concentration of these four proteins may be regulated by the cholinergic input to the hippocampus and the occipital cortex. The possibility exists that one or more of these proteins may be related to either the muscarinic or nicotinic cholinergic receptor in rat brain. PMID- 4027622 TI - Systemic and nigral application of amphetamine both cause an increase in extracellular concentration of ascorbate in the caudate nucleus of the rat. AB - Unmodified microvoltammetric electrodes and electrochemically modified cylindrical electrodes, both constructed from carbon fibers, were used to determine changes in ascorbate concentration in the caudate nucleus of the anesthetized rat following administration of amphetamine. The increased ascorbate levels with systemic amphetamine originate from a CNS source, since the response is not eliminated in adrenalectomized animals, and does not occur when p hydroxyamphetamine, an agent with peripheral actions similar to amphetamine, is used as a stimulus. Local application of amphetamine in the caudate nucleus results in an increase in catechols. However, this procedure results in a decrease of the extracellular concentration of ascorbate. Unilateral nigral infusion of dopamine or amphetamine leads to a significant increase in the concentrations of ascorbate detected bilaterally in the caudate nuclei with in vivo electrochemistry. In contrast, the paradigm causes a decrease in extracellular catechols on the ipsilateral side and an increase on the contralateral side. These experiments demonstrate that the extracellular level of ascorbate is not correlated with dopamine secretion. Furthermore, the data show that the action of amphetamine on ascorbate concentration in the caudate nucleus is in part mediated by the nigral actions of amphetamine. PMID- 4027623 TI - Projection of the digit and wrist area of precentral gyrus to the putamen: relation between topography and physiological properties of neurons in the putamen. AB - The autoradiographic technique was used to examine the projection from the digit and wrist area of the precentral gyrus to the putamen in two macaque monkeys. Motor responses elicited by intracortical microstimulation were mapped to guide selection of the site of injection of isotope. Additionally, an electrophysiological study of the activity of putamen neurons during voluntary movements of the distal arm in an awake monkey was performed prior to the anatomical study in one of the animals. Two major findings resulted from this study. Firstly, the area of representation of the digits and wrist in area 4 gives rise to a substantial projection to the putamen. The distribution of terminals consisted of a simple pattern of clusters at anterior levels of the putamen. At caudal levels in the putamen, the clusters merged into a single diagonal band of label. This basic pattern was found to be virtually identical in the two monkeys. Secondly, the location of neurons in the putamen which were activated during voluntary movements of the distal arm was closely associated with the terminal distribution of fibers from the digit and wrist zone of area 4. These data provide strong evidence to support the idea that the putamen is concerned with motor function of distal muscles of the arm, and that the topographic characteristics of the corticoputamen projection are closely related to the physiological properties of individual neurons in the putamen. PMID- 4027624 TI - 28 K cholecalcin (CaBP) levels in abnormal cerebella: studies on mutant mice and harmaline- and 3-acetylpyridine-treated rats. AB - The cerebellar Purkinje cells of both birds and mammals contain a specific calcium-binding protein, 28 K cholecalcin (CaBP). This is the same protein as the vitamin D-dependent kidney CaBP, but its Purkinje cell level is apparently vitamin D independent. The cerebellar CaBP contents of 3-acetylpyridine- and harmaline-treated rats and 5 mutant mouse strains (Purkinje cell degeneration, reeler, weaver, staggerer and nervous) were measured using a specific radioimmunoassay. The results indicate that the level of cerebellar CaBP is not dependent on the physiological state of the Purkinje cells but is an intrinsic measure of the size of the Purkinje cell population. PMID- 4027626 TI - Analgesia elicited by prefrontal stimulation. AB - Bipolar stimulating electrodes were placed into the medial prefrontal cortex (PFC) or control sites (occipital or cerebellar cortices) in adult male rats. Subsequently, it was determined that PFC stimulation resulted in a significant elevation of nociceptive response latencies, as tested using hot plate and tail flick techniques. Stimulation in control sites did not produce an increase in these response latencies. Rats receiving PFC stimulation were able to respond normally to various innocuous stimuli. Furthermore, seizures were not observed in these rats. These facts indicated that PFC stimulation did not disorient the animals nor inhibit their voluntary motor activity. The results of this study seem to indicate that the PFC is a site from which stimulus-produced analgesia may be elicited. PMID- 4027625 TI - Presaccadic 'spike' potential: investigation of topography and source. AB - Approximately 15-30 ms before a saccade, a large-amplitude, relatively short duration potential whose source has not previously been determined with certainty, can be recorded from the scalp in man. We have measured the surface topography of this potential during horizontal saccades in normal subjects and have found it to be maximal near the eye on the side ipsilateral to the direction of the saccade. Dipole modelling predicts a source near the eye ipsilateral to the direction of gaze, and the application of source derivation supports such an origin. Measurements of the potential close to the orbits in normal subjects and in patients with a unilateral abducens nerve palsy, exenterated orbit or ocular prosthesis suggest that it is a summation potential derived from the ipsilateral lateral rectus and contralateral medial rectus muscles. It is hypothesized that the potential may arise as a result of the synchronized recruitment of motor units in the extraocular muscles prior to the commencement of the saccade. PMID- 4027627 TI - Prefrontal influences upon the midbrain: a possible route for pain modulation. AB - After implanting stimulating electrodes in the prefrontal cortex (PFC) of adult male rats, the response to PFC stimulation was studied in widely scattered neurons of the midbrain. Subsequent testing was performed to determine if the firing rates of PFC-responsive neurons could also be altered by either a noxious stimulus (foot pinch) or the microiontophoretic administration of various neurotransmitter substances (methionine-enkephalin, ME; norepinephrine, NE; acetylcholine, ACh). Numerous mesencephalic neurons were identified which altered their spontaneous firing rates in response to PFC stimulation. Following PFC stimulation, most (71%) neurons decreased their firing rates. It was also noted that most (78%) PFC-responsive neurons were also responsive to noxious stimulation. Of these neurons, 65% altered their firing rates in a similar manner in response to both PFC and noxious stimuli. The remainder of the neurons which altered their firing rates in response to both PFC and noxious stimulation responded to the two types of stimuli in opposite manners. Of this latter type, it was found that when PFC and noxious stimuli were administered concurrently, PFC stimulation abolished the response to the noxious stimulus. It was also observed that the microiontophoretic administration of either ME or NE frequently (100% and 52% respectively) mimicked the response to PFC stimulation, thereby suggesting that these neurotransmitters may be involved in mediating the PFC influence upon neurons in the midbrain. PMID- 4027629 TI - Endogenous asymmetry of rat brain lipids and dominance of the right cerebral hemisphere in free fatty acid response to electroconvulsive shock. AB - An asymmetric distribution of free fatty acids (FFA) is shown to occur between right and left cerebral hemispheres (RCH, LCH) of the rat. The RCH contains 35% less FFA than the LCH, the difference being mainly accounted for by saturated and monoenoic fatty acids. Acute and chronic electroconvulsive shock (ECS) affects the distribution and apparent rate of fatty acid production differently in each hemisphere. Taking into consideration the basal content of each hemisphere, RCH produces significantly higher amounts of FFA during the acute tonic phase of the convulsion evoked by a single ECS. The largest increases correspond to arachidonic and stearic acids (1800% and 420% in RCH, 1200% and 330% in LCH, respectively). The hemispheric sidedness is evened out after successive ECSs. The removal of the released fatty acids is also faster in the RCH, as suggested by its lower FFA levels 5 min after a single shock (the acute condition) or after the last of a series of 5 daily shocks (the chronic condition). The endogenous FFA content and composition is altered by chronic ECSs. Thus, 24 h after the last of a series of 4 daily ECSs, total FFAs remain about 40% higher than in the controls for both hemispheres. Arachidonic acid increase amounts to 150%, doubling its percentage contribution to the FFA pool. The lower endogenous FFA content in RCH, its higher responsiveness to ECS, and its ability to more rapidly recover the pre-convulsive levels, suggest that the deacylation and reacylation of complex lipids are more active in this hemisphere.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4027628 TI - Localization and function of cat carotid body nicotinic receptors. AB - Acetylcholine and nicotinic agents excite cat carotid body chemoreceptors and modify their response to natural stimuli. The present experiments utilized [125I]alpha-bungarotoxin [( 125I]alpha-BGT) to localize within the chemosensory tissue the possible sites of action of exogenous and endogenous nicotinic cholinergic substances. In vitro equilibrium binding studies of intact carotid bodies determined a Kd of 5.57 nM and a Bmax of 9.21 pmol/g of tissue. Chronic section (12-15 days) of the carotid sinus nerve (CSN) did not change the amount of displaceable toxin binding. In contrast, the specific binding was reduced by 46% following removal of the superior cervical ganglion. Light microscope autoradiography of normal, CSN-denervated and sympathectomized carotid bodies revealed displaceable binding sites concentrated in lobules of type I and type II cells. Treatment of carotid bodies with 50 nM alpha-BGT in vitro reduced by 50% the release of [3H]dopamine (synthesized from [3H]tyrosine) caused by hypoxia or nicotine, and also significantly reduced the stimulus-evoked discharges recorded from the CSN. The data suggest an absence of alpha-BGT binding sites on the afferent terminals of the CSN and that nicotinic receptors located with parenchymal cell lobules may modulate the release of catecholamines from these cells. PMID- 4027630 TI - Topography of cholinergic perikarya and nerve fibres as well as cholinergic vesicles in the rat duodenum. AB - Using the acetylthiocholine staining method, it was possible to visualize acetylcholinesterase (AChE)-stained neuronal cell bodies and nerve endings as well as AChE-positive vesicles in the rat duodenum. AChE-reactive perikarya were seen with certainty only in the myenteric plexus. They were 40 micron in diameter and were mostly localized in groups within the ganglia (3-6 neurons per ganglion). Some thick, AChE-reactive nerve processes, running over a long distance in interconnecting nerve fibre strands, had their origin from AChE containing myenteric plexus perikarya. AChE-stained nerve fibres were detected in the myenteric and submucosal plexus as well as in the longitudinal and circular smooth muscle cell layer. AChE-positive nerve fibres were in close contacts with blood vessels, probably arterioles, Brunner's gland cells and epithelial cells. A conspicuously high density of AChE-positive nerve fibres was noted in the longitudinal smooth muscle layer, while AChE-stained nerve fibres were visualized only sporadically in the circular smooth muscle layer. Some Brunner's gland cells and epithelial cells contained AChE-reactive vesicles, which were constantly localized on the basal cell portion. The present findings might indicate that acetylcholine possesses important physiological roles as neurotransmitter and/or neuromodulator in the rat duodenum. PMID- 4027632 TI - Stability of the neuronal population of the dorsal lateral geniculate nucleus (LGNd) of aged rats. AB - The variations, with aging, of both neuronal and glial populations of the rat LGNd have been studied quantitatively. Our results show a stability of the total number of neurons of the rat LGNd with aging; this, plus the constant increase of the rat LGNd volume throughout rat life, causes the neuronal density to decrease slowly. Our data prove the necessity of determining the total number of neurons, not just neuronal density, in order to find out the actual evolution of the neuronal population with aging. Both glial cell number and density show an increase throughout rat life. PMID- 4027631 TI - Common neural mechanisms in experimental chorea and hemiballismus in the monkey. Evidence from 2-deoxyglucose autoradiography. AB - The autoradiographic 2-deoxyglucose uptake technique was used to visualise local cerebral metabolic activity in the monkey in recently developed models of chorea and hemiballismus. Unilateral dyskinesia was induced by injection of a gamma aminobutyric acid antagonist into the corpus striatum (in the case of chorea) or subthalamic nucleus (in the case of hemiballismus). Patterns of 2-deoxyglucose uptake suggest that during both forms of experimental dyskinesia the subthalamic nucleus and its projection to the globus pallidus are abnormally hypoactive. PMID- 4027633 TI - The suprachiasmatic nuclei and retinohypothalamic tract in the western spotted skunk. AB - The western spotted skunk has a well-developed retinohypothalamic tract projecting to the middle and caudal parts of the suprachiasmatic nuclei. The nuclei have a complex 3-dimensional shape and contain small neuronal somas. PMID- 4027635 TI - Lesions of the ventromedial hypothalamic nucleus enhance sympatho-adrenal function. AB - The effects of lesions of the ventromedial hypothalamic nucleus (VMH) on the sympatho-adrenal function were investigated in anesthetized rats using electrophysiological and biochemical techniques. Lesions of this nucleus produced a gradual but strong increase in the efferent activity of the adrenal sympathetic nerves. Catecholamine secretion from the adrenal medulla was also facilitated by VMH lesions. The results indicate that the catecholamines from the adrenal medulla might be involved in the development of metabolic disorders seen during VMH syndrome. PMID- 4027634 TI - Combined treatment with muscarinic and nicotinic cholinergic antagonists slows development of kindled seizures. AB - Rats were given daily injections of atropine, mecamylamine or both drugs in combination, 1 h prior to daily electrical amygdaloid kindling stimulation. Neither drug was effective alone, but the two drugs in combination significantly increased the latency to develop stage 5 kindled seizures. PMID- 4027636 TI - Temporary suppression of clonus in humans by brief photostimulation. AB - In this double-blind study, 21 subjects with spastic paraparesis due to chronic spinal cord injury received irradiation to the skin overlying the radial, median and saphenous nerves with a helium-neon laser (632.5 nm, 1 mW, 20 Hz) or sham treatment. Subjects in the experimental group demonstrated complete clonus suppression after 40 s of irradiation, an effect identical to that observed previously after peripheral electrical nerve stimulation. Subjects who received placebo did not demonstrate this phenomenon. Because such laser irradiation produces no detectable thermal effect, the results indicate that photochemical reactions initiated by laser may trigger neural activity. PMID- 4027637 TI - Functional activity of rat brainstem neurons regenerating axons along peripheral nerve grafts. AB - To investigate activation and discharge patterns of central nervous system neurons that regenerate lengthy axons along peripheral nerve grafts we inserted a 4 cm long autologous segment of sciatic nerve into the dorsolateral medulla oblongata of adult rats. Two to 6 months after grafting, the distribution of the cells of origin of the regenerating axons in many nuclei of the brainstem was documented by retrograde horseradish peroxidase labelling from the cut end of the grafts. Functional properties of neurons regenerating axons into the grafts were studied by recording from single regenerated fibers teased from the grafts. Conduction velocities of graft fibers ranged from less than 1 m/s to 25 m/s (30 degrees C). Spontaneous centrifugal impulse traffic in the grafts included units firing in bursts synchronously with the respiratory cycle. Activity in other units was either elicited or inhibited by natural or electrical stimulation of the periphery. Most units recorded in the grafts were neither spontaneously active nor responsive to stimulation of primary afferents. We conclude that: there are central nervous system neurons projecting into the grafts that respond to both excitatory and inhibitory transsynaptic influences; at least some of the spontaneous and induced activity recorded from axons in the grafts resembles that known for normal nerve cells in the regions of the brainstem from which axonal growth arises; and it is possible that many central neurons regenerating axons into peripheral nerve grafts have significantly reduced or altered synaptic inputs. PMID- 4027639 TI - Septohippocampal neurons in the rat: an in vivo intracellular study. AB - In vivo intracellular recordings were obtained from septohippocampal neurons identified by their antidromic response to electrical stimulation of the fimbria in rats anesthetized with pentobarbital or urethane. Beside the antidromic response, fimbria stimulation evoked a short-latency depolarizing potential (EPSP) followed by an hyperpolarizing potential which reversed polarity when recorded with KCl-filled electrodes. This IPSP is therefore likely to be chloride dependent. It was followed by a long-lasting (80-250 ms) depolarizing potential often associated with a burst of spikes. Septohippocampal neurons therefore receive an inhibitory, chloride-mediated, input which itself triggers a long lasting excitatory event. These results are consistent with extracellular observations. Their significance in the septohippocampal circuitry is discussed. PMID- 4027638 TI - Intrahypothalamic 5,7-dihydroxytryptamine: temporal analysis of effects on 5 hydroxytryptamine content in brain nuclei and on facilitated lordosis behavior. AB - The long-term relationship between serotonin (5-HT) levels in discrete hypothalamic nuclei and female rat sexual behavior, the lordosis response, was examined following intrahypothalamic injection of 5,7-dihydroxytryptamine (5,7 DHT). One week following 5,7-DHT injection, 5-HT levels in the ventromedial hypothalamic nucleus, dorsomedial nucleus, anterior hypothalamic nucleus and the medial preoptic nucleus were approximately 90% depleted as compared to sham animals. Other hypothalamic and preoptic areas including the arcuate-median eminence, vertical nucleus of diagonal band and lateral septal nucleus showed smaller reductions in 5-HT, from 40 to 70% of sham values. At this time estrogen dependent lordosis behavior in the lesioned group was facilitated. Behavioral facilitation was greatest at 4 weeks post lesion when depletion of 5-HT in the VMN was maximal. 5-HT levels increased at 57 days after 5,7-DHT treatment in most areas, and by 71 days post lesion, no significant differences in 5-HT levels were found between sham and 5,7-DHT-treated groups. Concomitant with the increases in 5-HT, facilitated lordosis behavior gradually decreased. Loss of behavioral facilitation appeared to be most closely related to increases in content of 5-HT in the ventromedial nucleus. These results further support the hypothesis that 5 HT endings in the hypothalamus exert tonic inhibitory regulation over hormone dependent lordosis in the female rat. They also indicate that regenerating 5-HT fibers in the hypothalamus can reinstate a normal pattern of hormone-dependent behavioral function. PMID- 4027641 TI - Simultaneous voltammetric and chemical monitoring of dopamine release in situ. AB - The validity of voltammetric monitoring of stimulated dopamine (DA) release was tested by simultaneous chemical assay of the extracellular fluid region next to the tip of a selective Nafion-coated graphite voltammetric electrode. Micro alumina probes were positioned next to the recording electrode tip to adsorb released catecholamines. The catecholamines were desorbed into microvolumes of acid and analyzed by very sensitive HPLC assays to provide unequivocal chemical verification of the electrochemical signals. The results fully confirm that selective voltammetric electrodes can detect released DA and that the concentrations determined voltammetrically or chemically agree well. PMID- 4027640 TI - Catecholamine concentrations in discrete brain nuclei and sympathetic tissues of genetically hypertensive mice. AB - Catecholamine concentrations were determined at central and peripheral level in high blood pressure (HBP), low blood pressure (LBP) and random bred (RB) mice. In HBP mice compared to LBP, the noradrenaline concentration was lower in the locus coeruleus, medullary A1-C1 and A2-C2 areas, thoracic spinal cord, posteroventral hypothalamus and nucleus hypothalamicus anterior, while dopamine concentration was decreased in the striatum. Adrenal catecholamine levels were higher in both HBP and LBP compared to RB mice. PMID- 4027642 TI - Sexual dimorphism in the numbers of neurons in the pelvic ganglia of adult rats. AB - The major pelvic ganglion in the adult rat differs in neuron number in the two sexes. The female pelvic ganglion has 5892 +/- 797 (mean +/- S.D.) neurons while the male contains 14,654 +/- 936. This sexual dimorphism in neuronal numbers in the autonomic nervous system is of interest because it suggests that endogenous hormone levels during development may have an influence on numbers of neurons in the adult pelvic ganglion. PMID- 4027644 TI - Inhibitors of calcium-dependent enzymes prevent the onset of afterdischarge in the peptidergic bag cell neurons of Aplysia. AB - Experiments with isolated bag cell neurons of Aplysia have produced evidence that changes in neuronal excitability may be brought about by the activation of calcium dependent enzymes such as calcium-dependent protein kinases. We have now examined the effects of agents which have been shown to inhibit several calcium dependent enzymes on the properties of bag cell neurons in situ. In response to brief electrical stimulation the bag cell neurons of Aplysia generate an afterdischarge during which they release neuroactive peptides. We have found that the ability of stimulation to trigger an afterdischarge in the bag cell neurons is inhibited by trifluoperazine (TFP, 50-100 microM), N-(6-aminohexyl)-5-chloro-1 napthalenesulphonamide (W7) (25-50 microM) and calmidazolium (40-100 microM), each of which has previously been shown to inhibit calmodulin-dependent enzymes and the calcium-phospholipid-dependent protein kinase in the bag cell neurons. Further analysis of the effects of TFP showed that this inhibition occurs at concentrations which do not inhibit synaptic transmission or the endogenous bursting of another neurosecretory neuron, R15. Secretion of neuroactive peptides from the bag cell neurons was measured both electrophysiologically and biochemically. No attenuation of secretion could be observed at concentrations of TFP below those which inhibited the initiation of afterdischarge. Our results indicate that these agents inhibit secretion from these neurons primarily by inhibiting the onset of the afterdischarge and are consistent with the hypothesis that a calcium-dependent enzyme plays a role in triggering the stimulus-induced transformation in the electrical properties of these neurons. PMID- 4027643 TI - Subcortical connections of area 17 in the tree shrew: an autoradiographic analysis. AB - The present anterograde autoradiographic study reveals several targets of the striate cortex (area 17) of the tree shrew which were not previously observed in studies which used anterograde degeneration methods; our data also confirm several previous findings. The results are discussed in the context of these projections modulating ascending visual information (claustrum, lateral intermediate nucleus, pulvinar, dorsal lateral geniculate, cells of the external medullary lamina, reticular nucleus of the thalamus, superficial collicular layers, and the anterior and posterior pretectal nuclei) or visuomotor information (putamen, caudate, ventral lateral geniculate, pontine gray, and the anterior and posterior pretectal nuclei). PMID- 4027645 TI - Action of acrylamide on selected enzymes of energy metabolism in denervated cat peripheral nerves. AB - The effect of acrylamide on selected glycolytic and citric acid cycle enzymes has been studied in denervated cat sciatic nerves in vitro and in vivo. The enzyme activity of glyceraldehyde-3-phosphate dehydrogenase (GAPDH), neuron specific enolase (NSE), succinate dehydrogenase (SDH), and lactate dehydrogenase (LDH), has been examined in saline-perfused, desheathed and denervated peroneal (P) and tibial (T) nerves from cats treated with acrylamide (15 mg/kg/day, s.c.) or vehicle for 15 days. GAPDH activity in denervated P and T nerve stumps was 2.0- and 2.3-fold higher than normal P and T nerve values. GAPDH activity in Schwann cells in denervated P and T nerves of acrylamide-treated cats was markedly reduced (56% and 61% of untreated denervated nerves, respectively). LDH and SDH activities were unaffected by acrylamide and NSE activity was absent in denervated nerve stumps. Acrylamide (0.5 and 20 mM) inhibited GAPDH activity in denervated nerve homogenates by 67% and 29%, respectively. This study demonstrates that acrylamide inhibits GAPDH in Schwann cells. The significance of GAPDH inhibition by acrylamide in denervated nerves and its relation to distal axonopathy has been discussed. PMID- 4027646 TI - Vision and the skin camouflage reactions of Ambystoma larvae: the effects of eye transplants and brain lesions. AB - Salamander larvae typically adapt their dermal melanophores to achieve camouflage, and it has been known for some time that removal of the eyes abolishes the response. Here we survey the contribution of the optic system to the bright and dark camouflage reactions and report that: the stimulus depends on an interaction between the direct and reflected light; an eye mounted atop the head and oriented vertically tended not to support camouflage, even though the animal responded to visual cues and learned a vision-dependent task; deviating the transplanted eye off the vertical axis enhanced the recovery of camouflage reactions; amputating or reorienting the telencephalon, epithalamus, pretectum or tectum did not abolish either camouflage reaction whereas lesions of the ventral optic pathway blocked brightening; transection near the midbrain-hindbrain junction--well posterior to known optic terminals--retarded the dark reaction; when the latter lesion was combined with disconnection of the telencephalon and epithalamus, contrary to predictions from the lesions executed separately, the animals lost the bright reaction; the hypophysis is necessary for darkening, but the organ supported this reaction even though detached, displaced or reoriented; and the pineal body was not essential for the grosser aspects of camouflage in Ambystoma larvae but may play an adjunctive role in fine tuning. PMID- 4027647 TI - The involvement of the anterior cingulate cortex in blood pressure control. AB - The visceromotor nature of the rat anterior cingulate cortex was investigated by electrically stimulating this area in both anesthetized and awake animals. Initial studies demonstrated that electrical stimulation of any division of the anterior cingulate cortex elicits a significant fall in blood pressure in the sodium pentobarbital-anesthetized rat. Depressor responses were greatest (up to 50% decreases) following stimulation of the ventral third of the anterior cingulate cortex. Heart rate was not altered by cingulate cortex stimulation. In the awake animal, stimulation of previously identified depressor sites in the rostral third of the pregenual cingulate cortex elicited pressor responses. In contrast, stimulation of the caudal third of this cortex elicited depressor responses, and stimulation of the middle third elicited biphasic (pressor followed by depressor) responses. These results indicate that the anterior cingulate cortex is a visceromotor region which may provide a cortical output for the regulation of blood pressure responses associated with learning and or stress. PMID- 4027648 TI - An anatomical study of ipsilateral retinal projections in the quail using radioautographic, horseradish peroxidase, fluorescence and degeneration techniques. AB - The topographical organization of ipsilateral retinal projections was investigated in the pigmented quail using different anatomical tracing techniques. The orthograde labeling patterns were examined after intraocular injections of tritiated tracers (autoradiography), horseradish peroxidase (HRP) either alone or combined with wheat germ agglutinin (WGA), the fluorescent tracer rhodamine beta-isothiocyanate (RITC) and after unilateral retinal ablations using degeneration methods where the material was observed at both light and electron microscope levels. The different techniques provided extremely variable results with regard to demonstrating ipsilateral retinal projections. Whereas the latter could not be revealed in the radioautographic preparations, the results derived using the degeneration and HRP methods were fragmentary. The RITC method was found to be the most effective and made it possible to accurately define the different ipsilateral optic contingents and their terminal arborizations within various thalamic, pretectal and tegmentomesencephalic centers. The contradictory data in the literature regarding the existence of ipsilateral retinal projections in various avian species may be explained by differences in methodology based upon the relative degrees of resolution offered by the different techniques. PMID- 4027649 TI - Analysis of muscarinic receptor concentration and subtypes following lesion of rat substantia innominata. AB - Cholinergic neurones located in the nucleus basalis of Meynert (NBM) in the substantia innominata (SI) of primates are known to project to cerebral cortex and cell loss in NBM is thought to be associated with the cholinergic deficit seen in Alzheimer's disease. We have examined in rats the effect of lesion of SI with kainate (1 microgram/0.5 microliter) on acetylcholine esterase (AChE) activity, muscarinic receptor number and subtypes in cerebral cortex at 1, 2 and 4 weeks. The area of lesion was assessed histologically. AChE activity was significantly reduced in frontal and parietal cortex ipsilateral to the lesion compared to the contralateral side by 37 and 30%, respectively, at 1 week. The reduction in parietal cortex at 4 weeks (16%) was significantly attenuated. Muscarinic receptor number was reduced in cerebral cortex ipsilateral to the lesion at the 3 time periods measured, being reduced by 14 and 17% in the frontal and parietal cortex, respectively, at 1 week. Changes in receptor number and AChE activity correlated with the size of lesion. Low affinity agonist binding sites and high affinity pirenzepine binding sites were also analyzed and found to be significantly reduced by lesion of SI. The proportions of high and low affinity agonist binding sites and subtypes of pirenzepine binding sites were, however, not significantly affected by lesion. PMID- 4027652 TI - Electroencephalographic activity after kainic and ibotenic acid injections in the amygdaloid complex of rats. AB - Long-term electroencephalographic (EEG) activity and neuropathological effects were studied after unilateral amygdaloid injections of kainic acid (KA) and ibotenic acid (IBO). Injections of 0.2 microgram KA caused severe epileptiform activity which lasted up to postoperative day 49. Complete losses of neuronal and glial elements appeared as cavities within the injected areas. Epileptiform activity after injections of 3.0 micrograms IBO was seen only as interictal spikes which lasted for 2-4 h after surgery. Cavities within the lesion areas were also evident in the IBO-injected rats. The results suggest that KA should be avoided as a lesion method in behavioral studies of brain functions, whereas IBO is judged to be a more suitable lesion tool, which produces only transitory and negligible epileptiform activity. However, neither KA nor IBO seems to have long term fiber-sparing properties. PMID- 4027650 TI - Neuron-specific mitochondrial degeneration induced by hyperammonemia and octanoic acidemia. AB - The neuropathological consequences of acute exposure to the neurotoxicants ammonia and octanoic acid were investigated with the isolated, perfused canine brain preparation. After 1 h of combined hyperammonemia and octanoic acidemia, ultrastructural changes were apparent in all brain regions examined. The cell bodies of neurons were the primary sites of these alterations. Neuronal mitochondria were distended, and the lamellae of the mitochondrial cristae were separated. In some cases the lamellae had completely dispersed, leaving only matrix remnants. Mitochondria of adjacent astrocytes appeared normal. Thus, a characteristic population of brain mitochondria is selectively vulnerable to a combination of hyperammonemia and octanoic acidemia and may be related to the biochemical mechanisms underlying encephalopathies of hepatic origin. PMID- 4027651 TI - An assessment of the antinociceptive and aversive effects of stimulating identified sites in the rat brain. AB - At many sites in the brain electrical stimulation with low current intensity is both aversive and causes antinociception. In view of the well documented antinociception caused by various types of stress and pain it is possible that in some parts of the brain the antinociception is secondary to the stress of the stimulation. At 114 sites in the rat brain the intensity of stimulation required to evoke an aversive response has been compared with the antinociceptive current intensity. Only stimulation in the dorsal hippocampus and pretectal area caused antinociception without significant aversion. Strong aversion resulted from stimulation of 46% of the sites including the central gray and nucleus raphe magnus. Antinociception was significantly correlated with the aversiveness of the stimulation although in 15% of the stimulation sites strong aversion was seen with no antinociception. It is concluded that there can be little justification in assigning a primary antinociceptive role to a brain area which evokes strong escape reactions when stimulated. PMID- 4027653 TI - Axonal transport of alpha-bungarotoxin binding sites in rat sciatic nerve. AB - [125I]alpha-Bungarotoxin (alpha-BuTX) binding sites accumulate both proximal and distal to a ligature positioned around the sciatic nerve of rats. [125I]alpha BuTX binding sites, localized using quantitative receptor autoradiography, were found to accumulate at nerve ligatures at a relatively constant rate which suggests that they undergo both anterograde and retrograde axonal transport. [125I]alpha-BuTX binding to sections of ligated sciatic nerve was saturable with apparent dissociation constants of 0.97 nM proximal and 0.53 nM distal to the ligature. D-Tubocurarine, nicotine, decamethonium and atropine displaced [125]alpha-BuTX from sciatic nerve sections with affinities comparable to those previously reported for the toxin binding component of rat brain. These data indicate that [125I]alpha-BuTX binding sites pharmacologically similar to those of rat brain are transported in sciatic nerve. Axonally transported toxin binding sites may correspond to those previously localized to the plasma membrane of peripheral nerve axons and on the terminals of motor neurons. PMID- 4027654 TI - Effects of water deprivation and deamino [8-D-arginine] vasopressin on [14C]2 deoxyglucose uptake by the hypothalamo-hypophysial system in mice with hereditary nephrogenic diabetes insipidus. AB - The effects of water deprivation and the injection of deamino [8-D-arginine] vasopressin (dDAVP) on the metabolic activity of the hypothalamo-neurohypophysial neurones of mice with inherited nephrogenic diabetes insipidus (DI +/+ Severe) have been investigated by quantitative autoradiography using the [14C]2 deoxyglucose (2-DG) technique. The relative metabolic activities (rma) of the paraventricular nuclei (PVN) and pars nervosa (PN) in severely diabetic mice were not significantly different from the rma of the PVN and PN in Non-severe or Normal mice, but the rma of the pars distalis (PD) was greater in the Severe mice than in the other two strains. Water deprivation (4-5 h) significantly increased the rma of the PVN and PN in Severe mice compared with those in Non-severe mice that had been similarly deprived of water. The increased rma of the PVN and PN produced by water deprivation in Severe mice was not reduced to normal by injection of dDAVP. The injection of dDAVP alone had no effect on the rma of the PVN or PN, but dDAVP injection alone, water deprivation alone, or both treatments combined decreased the rma of the PD in Severe mice. Neither the supraoptic nuclei (SON) nor any of the other 19 brain areas studied were affected, in terms of rma, by either water deprivation, injection of dDAVP, or both.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4027655 TI - Evaluation of neuronal connectivity: sensitivity of cross-correlation. AB - Cross-correlation analysis of separable multi-unit activity is one of the most commonly used methods to investigate connectivity in neural networks. In the course of development of new analysis techniques which go beyond the study of pairs or triplets of neurons, the need arose for a simple yet versatile simulator to generate spike trains from networks of specified structure. The present paper describes such a simulator and presents some examples of its performance as analyzed by cross-correlation. We noted a distinct asymmetry in the sensitivity of cross-correlation for the presence of excitatory vs inhibitory connections. A theoretical analysis is given from which quantitative criteria for detectability were derived. It appears that indeed the sensitivity of cross-correlation for excitation is larger to an order of magnitude than it is for inhibition. Possible consequences of this finding are indicated, and the relation to commonly used methods to measure strength of interaction are discussed. PMID- 4027656 TI - Muscarinic cholinergic receptors in the retina of the larval tiger salamander. AB - The pharmacology and autoradiographic localization of muscarinic cholinergic receptors in retinal slices of the larval tiger salamander have been examined using the muscarinic antagonist [3H]propylbenzilylcholine mustard. Under the conditions of these experiments the binding of this ligand is irreversible. Saturation and maximum specific binding of 270 pM of ligand per gram protein are observed after an incubation of 1 h, and autoradiographic studies show that this does not reflect surface binding alone. Muscarinic but not nicotinic drugs suppress the binding of propylbenzilylcholine mustard at physiologically relevant concentrations; half-maximal suppression of binding by the muscarinic antagonists atropine sulfate and quinuclidinyl benzilate occurs, respectively, at 9.0 and 7.5 X 10(-10) M. Light microscopic autoradiography reveals the discrete localization of the ligand to the sites of synaptic contact, the retinal plexiform layers, predominantly the inner plexiform layer. The implications of the present study on current theories of cholinergic function in the vertebrate retina are discussed. PMID- 4027658 TI - Electrophysiological analysis of the tecto-olivocerebellar (lobule VII) projection in the rat. AB - In albino rats the superior colliculus was stimulated and its evoked potentials were explored throughout the posterior vermis of the cerebellum. Climbing fiber responses were identified only in lobule VII, ipsilaterally 1.2-1.6 mm wide. In the medial accessory olive, subnucleus c, in the contralateral side both antidromically evoked potentials from lobule VII and orthodromically evoked potentials from the superior colliculus were recorded. This evidence suggests that they are tecto-olivocerebellar projections. PMID- 4027659 TI - Fast axonal transport in the visual pathway of the chick and rat. AB - Young chickens and rats were injected intravitreally with [3H]proline and sacrificed at short intervals thereafter. Regression lines calculated for the plotted points (survival time, transport distance) revealed a transport rate of 329 mm/day in the chick and 350 mm/day in the rat. Both rates are close to those reported for peripheral axons (410 +/- 50 mm/day). PMID- 4027657 TI - Selective depression of hippocampal inhibitory postsynaptic potentials and spontaneous firing by volatile anesthetics. AB - The effects of halothane, isoflurane and enflurane on the rat hippocampal CA1 neurons in in vitro preparations were studied by intracellular recordings. All volatile anesthetics, at the concentrations which are likely to be in the range of clinical doses, depressed the IPSPs and the spontaneous firing without affecting the resting membrane properties and the EPSPs. The results suggest that the simultaneous blocking effects of the anesthetics on both the spontaneous firing and IPSPs are responsible for production of general anesthesia rather than their blocking actions on the EPSPs in terms of behavior of hippocampal neurons. PMID- 4027660 TI - Differences between strychnine and penicillin epileptogenesis suggest a laminar organization of neocortical inhibition. AB - Transient foci of epileptiform alteration in neuronal population activity were induced by microinjection of strychnine sulfate into different layers of cat striate cortex. Potentials evoked by visual field-specific photic stimulation were recorded from microelectrodes at the injection site and in adjacent laminae. Epileptogenesis, characterized by an enhancement of the normal primary response followed by the development of a large late potential, occurred only with strychnine injections into superficial pyramidal layers 2 and 3. By contrast, stellate layer 4 has been shown to be most susceptible to epileptogenic effects of penicillin and bicuculline. Since disinhibitory convulsants should be most effective where their actions antagonize the prevalent type of inhibition, these findings suggest that there may be a laminar segregation of neocortical inhibition, possibly glycine-mediated in layers 2-3 and probably gamma aminobutyric acid (GABA)-mediated in layer 4. PMID- 4027661 TI - Morphometric analysis of medial basal hypothalamic neuronal degeneration in diabetes (db/db) mutant C57BL/KsJ mice: relation to age and hyperglycemia. AB - Age- and diabetes-related neuronal degenerative changes were morphometrically evaluated in the arcuate (ARC) and ventromedial (VMH) hypothalamic nuclei of control (+/?) and diabetic (db/db) C57BL/KsJ mice between 4 and 16 weeks of age. By 4 weeks of age, (db/db) mice exhibited marked obesity and hyperglycemia relative to controls. An increase in the population of degenerated ARC neurons was detected at 8 weeks of age in (db/db) mice relative to (+/?) animals. By 16 weeks of age, a significant increase in the number of degenerated VMH neurons in (db/db) mice was found, relative to controls. In addition, the neuronal density (neurons/mm2 area of nucleus) of both the ARC and VMH nuclei was found to be depressed in (db/db) mice, relative to controls, by 16 weeks of age. These data suggest that the normal degenerative loss of ARC and VMH neurons that occurs with age in normal mice is enhanced in the (db/db) mouse. These findings suggest that a functional alteration in hypothalamic nuclei which are recognized to modulate autonomic, pancreatic and pituitary activity may be associated with the onset or expression of the diabetic condition in the C57BL/KsJ (db/db) mouse. PMID- 4027662 TI - Neuronotrophic factors for mammalian brain neurons: injury induction in neonatal, adult and aged rat brain. AB - Tissue from neonatal, adult and aged Sprague-Dawley rat brain contained low levels of survival promoting activity for embryonic neurons from various rat brain regions. This basal neuronotrophic activity was 2-fold higher in adult and 4-fold higher in aged rat brain, with respect to that in neonatal brain. Tissue extracts also contained 4-fold higher levels of neuronotoxic activity in adult and aged than in neonatal brain. Ablation of the occipital/entorhinal cortex caused a 3-fold increase in neuronotrophic activity in the tissue surrounding the wound in neonates and 4-fold in adult and aged brain, with respect to the basal levels. Maximal activities occurred at 3 days, 6 days and 15 days postlesion in neonatal, adult and aged tissue respectively, and subsequently returned to basal levels. Neuronotoxic activity was not induced following injury. The slower neuronotrophic response to injury in older animals may be one of the determinant factors of the slower recovery from brain damage observed in aging. PMID- 4027663 TI - The impact of aging on luteinizing hormone (LH) and thyroid-stimulating hormone (TSH) in the rat brain. AB - Immunoreactive and bioactive luteinizing hormone (LH), thyroid-stimulating hormone (TSH) and growth hormone (GH) have been described by this and other laboratories to be present in discrete areas of the rodent and primate brain. In the present studies, LH and TSH concentrations in serum, pituitary, hypothalamus, brainstem, cerebellum, cerebral cortex and hippocampus were measured in male Sprague-Dawley rats at 2.5 months of age, when 11-12 months old and at 24 months of age. There was a significant decrease in hypothalamic TSH concentrations in the 11-12-month-old rats compared to younger animals (672 +/- 127 ng/mg vs 86 +/- 17 ng/mg, P less than 0.001). This was unaccompanied by any changes in TSH levels in serum, anterior pituitary, or in any of the extrahypothalamic brain areas that were examined. In contrast, there was a significant 50% drop in LH concentrations in the anterior pituitary gland of 11-12-month-old animals when compared with young controls (72 +/- 58 micrograms/mg vs 137.2 +/- 27 micrograms/mg, P less than 0.05) without any noted change in serum or brain LH concentrations. Similar decreases in LH concentration were also seen in the anterior pituitary glands of two-year-old animals. These discordant profiles between pituitary and brain LH and TSH provide additional circumstantial evidence that these brain peptides do not represent contaminants from the anterior pituitary. Further, these significant changes in TSH and LH concentrations that develop with aging may implicate these particular peptides in the development of certain features of senescence. PMID- 4027664 TI - The influence of permanent odor stimuli on the postnatal development of neural activity in the olfactory bulbs of laboratory mice. AB - Young laboratory mice were kept from birth in a surrounding with one dominating synthetical odor substance (geraniol, C10H18O; experimentals); the controls were bred under normal conditions. Between postnatal days 10 and 35 the development of the neural activity in the olfactory bulb and the response to the synthetical (geraniol) and a natural odor (nest material) were tested at 6 different stages of age. By means of a computer the total energy and the frequency composition (power spectra) of the electrophysiologically leaded potentials were analyzed at the time of stimulation and without stimulation. The developmental increment of neural activity was retarded at the experimentals, but the typical high-frequency waves (oscillations) appeared about 5-6 days earlier than in the controls. Both odor substances induced neural responses measured by energy and frequency changes in the power spectra. In controls none of the odors leads to noticeable changes in the composition of frequencies at days 10 and 14. Beginning at postnatal day 18 the odor substances of nest material evoked increasing neural reactions; at all stages of age geraniol induced only slight alterations in the power spectra. In the experimentals responses could be measured first at day 14. The changes in power spectra rapidly increased in the following 3 weeks and the responses to geraniol reached several times more intense levels than in the controls. The influence of permanent olfactory stimuli on the ontogenetic development of the olfactory bulb and the extreme plasticity of this system are discussed. PMID- 4027665 TI - The effects of protein deprivation on neuronal migration in rats. AB - Although there is extensive literature documenting the effects of undernutrition on brain development, most studies have been concerned with cell differentiation with little attention given to neuronal migration. In a rat model we have investigated the effect of chronic protein deprivation on cell migration from the anterior lateral ventricle to the olfactory bulb. By using standard autoradiographic techniques and comparing the position of heavily labeled cells within the migratory stream, we estimated the migration rate to be 100 microns/h in 25%-casein-diet rats and between 33 and 70 microns/h in 8%-casein-diet rats. We therefore conclude that migration is slowed in chronically protein-deprived rats and this slowed migration may be related to subsequent abnormalities of cell differentiation seen in protein-deprived rats. PMID- 4027666 TI - Neurogenesis in tissue cultures of adult teleost spinal cord. AB - [3H]Thymidine autoradiography of explant cultures from the spinal cord of an adult teleost, Sternarchus albifrons, reveals the presence of thymidine-labeled cells with neuronal morphology. These cells have also been identified as neurons by positive staining with two monoclonal antibodies against neurofilaments. Thymidine labeling occurs in cultured neurons derived from both normal (histologically and functionally mature) and regenerating spinal cord of adult Sternarchus albifrons. These results provide evidence that some cells in spinal cord of adult Sternarchus retain the ability to incorporate thymidine and undergo neuronal differentiation in vitro. PMID- 4027667 TI - A demonstration of two distinct geniculocortical projection patterns in albino ferrets. AB - The geniculocortical pathways of albino ferrets have been studied by injecting lectin bound horseradish peroxidase into the visual cortex and then studying the geniculate distribution of retrogradely labelled cells in the dorsal lateral geniculate nucleus. It has been shown that in ferrets, as in Siamese cats, there are two quite distinct patterns of geniculocortical projection. One of the patterns seen in ferrets is comparable to the 'Midwestern' pattern previously described in Siamese cats, while the other is comparable to the 'Boston' pattern. PMID- 4027668 TI - The organization of the lateral geniculate nucleus and of the geniculocortical pathway that develops without retinal afferents. AB - The fine structure and cortical connections of the dorsal lateral geniculate nucleus have been studied in postnatal (3.5-14-month-old) ferrets in which all retinal afferents had been removed prenatally at the time these fibers are first starting to invade the nucleus. The synaptic profiles in the mature nucleus show the cytological characteristics and arrangements that would remain if the retinal afferents were removed, with no significant compensatory ingrowth of foreign specific afferents. The nucleus is reduced in overall volume, but the geniculocortical and corticogeniculate interconnections show an essentially normal topography. Although in these experiments the geniculocortical projections can establish a normal topographic pattern in the absence of retinal afferents an accompanying paper shows that this topographic pattern can also be modified in the presence of abnormal retinogeniculate inputs. We conclude that two separate mechanisms contribute to the formation of retinal maps within the geniculocortical pathways and that different interactions between these two mechanisms produce the different patterns of abnormal geniculocortical pathways that have been described in pigment-deficient cats, mink and ferrets. PMID- 4027669 TI - Development of sensitivity to GABA and glycine in cultured cerebellar neurons. AB - The effects of iontophoretically applied gamma-aminobutyric acid (GABA) and glycine on developing cerebellar neurons cultured for 7-40 days were intracellularly investigated. All neurons tested dose-dependently responded to both GABA and glycine. In mature neurons (after 25 days in culture) these amino acids inhibited spontaneous spikes, decreased the membrane input resistance and induced either hyperpolarization or depolarization of membrane potential. The mean reversal potential was -47 mV for GABA and -43 mV for glycine. Immature neurons, 7-12 days in culture, which were not spontaneously firing, also behaved in a similar manner as the mature ones, though the membrane resistance was not so largely changed by GABA or glycine and the reversal potential was more positive ( 39 mV for GABA, -37 mV for glycine). These reversal potentials were shifted toward 0 mV by lowering the external Cl- concentration in either mature or immature neurons. The effects of GABA and glycine on mature or immature neurons were more or less inhibited by all of picrotoxin, bicuculline and strychnine. The effective concentrations of these antagonists, however, were lower in general in immature neurons. In mature neurons, picrotoxin and bicuculline became more selective to GABA than glycine and strychnine became more selective to glycine than GABA. These results suggest that sensitivities to GABA and glycine differentiate into selective types in the course of maturing of cerebellar cultured neurons. PMID- 4027670 TI - The effects of neonatal thyroid deficiency on acetylcholine synthesis and glucose oxidation in rat corpus striatum. AB - The effects of propylthiouracil (PTU)-induced thyroid deficiency on [14C]acetylcholine synthesis and 14CO2 production from [U-14C]glucose in vitro, by fine prisms of the corpus striatum were investigated in developing rats. Consistent with deficits in choline uptake and choline acetyltransferase activity (Kalaria et al.17), PTU-treatment from two days after birth significantly impaired (27-39%) [14C]acetylcholine synthesis in striatal tissue taken from 3- or 6-week-old animals. In the thyroid-deficient (Tx) animals, 14CO2 production from [14C]glucose was unchanged in incubations in the presence of 5 mM K+ but was significantly reduced (33%) in medium with 31 mM K+ concentration. The addition of 10 mM DL-3-hydroxybutyrate in incubations with 5 mM K+ persistently inhibited 14CO2 production by striatal samples from the Tx rats. The fraction acetylated of [3H]choline accumulated by striatal prisms was unaffected by the PTU-induced thyroid deficiency. These findings suggest the development of fewer cholinergic nerve terminals in striatum during neonatal thyroid deficiency. Cholinergic nerve terminals that develop seem unaffected in their capacity for K+-stimulation and in their ability to acetylate transported [3H]choline. PMID- 4027672 TI - Quantitative studies of mitoses in cerebral hemispheres of fetal rats. AB - In continuation of our study of 15-day fetal rat brain development, evidence was obtained of a single layer of mitoses, situated away from the ventricle at a mean depth of 75% of the thickness of the cell layer of cerebral hemispheres ('deep mitoses'). Their number is 17.9% of ventricular mitoses and their spindles are perpendicular to spindles of ventricular mitoses. Their distribution is not correlated with distribution of ventricular mitoses. The fate and destination of these deep mitotic cells is at present unknown; the possibility that they are mitoses of the capillaries has been discussed. PMID- 4027673 TI - Effects of neonatal castration or treatment with dihydrotestosterone on numbers of neurons in the rat superior cervical sympathetic ganglion. AB - There is a normal sexual dimorphism in the number of neurons in the rat superior cervical sympathetic ganglion (SCG), with adult males having more neurons in this ganglion than females. We confirm this finding here, report that this sex difference is not present at birth and that neonatal castration of males reduces the adult sex difference. These results indicate that perinatal levels of circulating testicular hormones play a role in regulating the numbers of neurons in the SCG. Treatment of neonatal rats with testosterone propionate or estradiol significantly increases the number of neurons in the SCG. To determine whether this effect is primary androgenic or estrogenic, the effects of dihydrotestosterone, on SCG neuron number were investigated. Dihydrotestosterone, unlike testosterone, is not aromatized to estradiol intracellularly. There was no difference in the number of neurons between animals injected from birth with vehicle or dihydrotestosterone. This difference in effects between dihydrotestosterone and testosterone suggests that the actions of testosterone may be via aromatization to estradiol, rather than action at an androgen receptor. PMID- 4027674 TI - Con A-binding glycoproteins in the developing cerebellum of control and hypothyroid rats. AB - Concanavalin A (Con A)-binding glycoproteins were studied during the postnatal development of the cerebellum of control and hypothyroid rats. Only 4 glycoprotein bands have a transient behavior in control animals. They progressively increase until the 13th day and markedly decline between the 15th and the 18th postnatal day. In the cerebellum of hypothyroid rats, the level of these compounds is greatly reduced and the previous decrease observed in controls is not found again. This defect of Con A-binding glycoproteins mainly localized on the plasma membrane of parallel fibers might be related to the reduced synaptogenesis observed in the molecular layer of hypothyroid rats between parallel fibers and Purkinje cell dendritic spines. PMID- 4027671 TI - Developmentally induced loss of direction-selective neurons in the cat's lateral suprasylvian visual cortex. AB - Single-cell recordings were carried out in the posteromedial lateral suprasylvian (PMLS) visual cortex of cats reared in an environment illuminated by 8-Hz stroboscopic flashes. These cats had a reduced proportion of direction-selective cells (8%) compared to PMLS cortex of normal cats (79%). Other receptive-field properties and ocular dominance of the neurons appeared normal. These results have implications for understanding the mechanisms of PMLS-cortex development and for interpreting behavioral studies of strobe-reared cats. PMID- 4027675 TI - Acetylcholinesterase activity in the developing olfactory bulb: a biochemical study on normal maturation and the influence of peripheral and central connections. AB - In the newborn rat olfactory bulb (OB), the specific activity of acetylcholinesterase (AChE) is about 20% of the adult value. During postnatal development, the specific activity remains unchanged until day 10; a growth spurt of 5X is observed between days 10 and 25, when adult values (90 nmoles ACh/min/mg protein; 6 nmol/min/mg wet wt.) are reached. However, total activity shows continuous increase slowly at first and rapidly between days 10 to 30, reaching a plateau by day 60. Between birth to day 60 total activity increases 65X. To determine the influence of peripheral and central connections on the development of AChE activity in the OB, rats were subjected to unilateral olfactory denervation and/or transection of olfactory peduncle, carried out either neonatally or at day 30; the bulbs were assayed a month later (days 30 and 60 respectively). It was found that in both neonatal and 30-day-old rats, denervation caused a 15% decrease in total activity, while transection led to more than 60% reduction. In the older rats, the reduction due to transection represented the degenerative loss of activity, but in the neonatally transected bulbs the growth of some cholinergic elements continued although very slowly. Between birth to day 30, total AChE activity increased only 12X in completely isolated OB, 25X in transected OB and 40X in denervated OB, compared to 45-50X in control OB. In the transected and isolated bulbs specific activity of AChE was also reduced significantly (25-50% depending on age and operation). These results suggest that while centrifugal fibers are the main source of cholinergic activity in the mature as well as the developing OB, the olfactory nerve and some intrabulbar sources such as cholinergic cells or cholinoceptive membranes also contribute to AChE activity in the OB. These intrinsic sources of AChE activity can persist and even show some growth in the developing olfactory bulb in the absence of the centrifugal fibers and/or the olfactory afferents. PMID- 4027676 TI - Nerve growth factor and dexamethasone specify the catecholaminergic phenotype of cultured rat chromaffin cells: dependence on developmental stage. AB - Antibodies to epinephrine (E) and bovine phenylethanolamine N-methyltransferase (PNMT) have been used to monitor the regulation of the E- and PNMT-immunoreactive chromaffin cell phenotypes by dexamethasone (DEX) and nerve growth factor (NGF). The cells were isolated from 1-, 10- and 30-day-old (D1, D10 and D30) rat adrenal glands and grown for 4 days on a polyornithine substratum. DEX (10(-5)M) supported the survival of 90% of the cells from all postnatal ages studied. In contrast, only 45% (D1), 33% (D10) and 60% (D30) of the chromaffin cells had survived after 4 days in control cultures or when treated with NGF (100 ng/ml). Throughout this study numbers of E-immunoreactive cells were approximately 10% larger than those of cells stained by anti-PNMT antibodies irrespective of the treatments applied. 55% of the cells isolated at D1 and 79% of the cells at D10 were stained by anti-E antibodies. The proportion of E-positive cells was constant in D1 cultures carried for 4 days, while E-immunoreactive cells dropped to 63% in cultures from D10. At D1 and D10 DEX and NGF had opposite effects on the portions of E-positive cells, DEX increasing and NGF decreasing their relative numbers, 66% of the chromaffin cells isolated at D30 displayed E specific immunoreactivity. DEX caused a significant increase (to 74%), while both NGF-treated and control cultures exhibited a decrease in the relative numbers of E-immunoreactive cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4027677 TI - Identification of synapses formed by the aberrant, uncrossed retinogeniculate projection in the hamster after neonatal monocular enucleation. AB - The terminals of the abnormally enhanced, stabilized uncrossed retinogeniculate projection in adult hamsters produced by removal of one eye at birth, were labelled by injection of HRP into the remaining eye and examined by electron microscopy. Labelled terminals closely resembling normally positioned retinal terminals were found to make well-differentiated synaptic contacts with geniculate projection and interneuron-like cells in regions of the dorsal lateral geniculate nucleus that do not receive uncrossed retinal input in normal adult animals. PMID- 4027678 TI - Decreased number of cells in the inferior olivary nucleus of the developing staggerer mouse. AB - Light-microscopic study and cell counts of the inferior olivary nucleus (ION) were performed in staggerer mutant mice and compared to those obtained in C57B16J controls. The main result is that 60% of the olivary cells are missing in 24-day old mutants and that most of the deficit is already present on postnatal day 10. It has been previously shown that the staggerer gene exerts an intrinsic effect on the Purkinje cells. Whether cells of the inferior olive are, in addition to Purkinje cells, a primary site of gene action, or whether they are retrogradely affected by the cerebellar malformation, remains unknown from the present study. PMID- 4027679 TI - Temporal retina is preferentially represented in the early retinotectal projection in the hamster. AB - Retrograde transport of horseradish peroxidase (HRP) after complete transection of the brachium of the superior colliculus on the day of birth in hamsters revealed preferential labelling of the temporal retina. Cytochrome oxidase staining of the retina showed similar preferential temporal labelling. A discrete lack of label of the extreme temporal periphery of the retina contralateral to the HRP placement and a complementary label of ipsilateral temporal periphery were also observed. PMID- 4027681 TI - Extensive target cell loss during development results in mossy fibers in the regio superior (CA1) of the rat hippocampal formation. AB - The axons of dentate granule cells (mossy fibers) have been reported to appear in the regio superior (CA1) of the rat hippocampal formation following destruction of the pyramidal cells in the regio inferior (CA3). We undertook the present experiments to confirm this finding and to determine the requirements for this dramatic neuronal rearrangement. We found that extensive (greater than 80%) loss of CA3 cells, as well as the presence of surviving CA1 neurons within a narrow period of development (postnatal days 3-5) is necessary, however apparently not sufficient, for the appearance of CA1 mossy fibers. That the absence of normal target cells during a restricted period of mossy fiber development will lead to their association with novel targets suggests that much of the specificity of this developing connection depends on the presence of normal targets during a critical period. PMID- 4027680 TI - Fetal retinae transplanted over tecta of neonatal rats respond to light and evoke patterned neuronal discharges in the host superior colliculus. PMID- 4027682 TI - Motoneurone survival and neuritic outgrowth promoted by different cell types in embryonic muscle. AB - Different cell types within developing chick skeletal muscle were assayed for their ability to release factors into culture media which could affect the survival and neuritic development of labelled motoneurones and lateral motor column explants. Enriched cultures of myotubes, myoblasts, fibroblasts and mesenchyme were prepared by selective preplating and trypsinisation techniques. Degrees of enrichment were assessed immunofluorescently and morphologically; fibroblasts were the main contaminating cell type. Medium conditioned over each cell type was then tested in dose-response assay against both explants and dissociated motoneurones. In both cases the myotube conditioned medium (MCM) promoted the greatest levels of both survival and neuritic outgrowth, and had the greatest relative potency of all of the cell types. When MCM was preincubated over polycationic substrata, it lost the ability to promote neuritic growth; this could be restored if fresh conditioned medium (CM) was added to the cultures. Thus it was demonstrated that within the MCM there are physically separable agents responsible for neurone survival and neurite expression. The neurite promoting factor (NPF) within the MCM was stable to collagenase, deoxyribonuclease, neuraminidase and chondroitinase ABC, but was destroyed by trypsin and heparinase. These results imply that a heparan sulfate proteoglycan is essential for the activity of the factor. PMID- 4027684 TI - Glycoprotein composition and turnover in subcellular fractions from the cerebral cortex of normal and reeler mutant mice. AB - Twenty-day-old reeler and normal mice were either injected intraventricularly with radiolabelled fucose before subcellular fractionation of the cerebral cortex followed by SDS-PAGE, or gels of such fractions were overlaid with [125I]concanavalin A (ConA). While there were no differences in polypeptide profiles of normal and reeler subcellular fractions there were marked differences in the abundance of particular ConA-binding glycoproteins and in fucose incorporation into particular glycoproteins, especially in the synaptic plasma membrane (SPM) and 100,000 g soluble fractions. In addition there was a significantly lower binding (greater than 50%) of quinuclidinyl benzilate to reeler microsomal and SPM fractions as compared with normal. The differences in glycoprotein expression may be pertinent to anatomical observations of abnormal interactions between neurons and glial fibres during development of the reeler cerebrum. PMID- 4027683 TI - Formation of the sexually dimorphic nucleus of the preoptic area: neuronal growth, migration and changes in cell number. AB - The sexually dimorphic nucleus of the preoptic area (SDN-POA) appears to be a morphological marker of the process of sexual differentiation of the rat brain. A portion of the presumptive SDN-POA neurons can be specifically identified utilizing autoradiography following the administration of [3H]thymidine on day 18 of gestation. In the present study we have utilized this fact in order to describe the general pattern of formation of the SDN-POA during the perinatal period. Following the administration of [3H]thymidine, fetal pups were sacrificed and perfused with neutral formalin either two hours after the injection or on day 20 or 22 postfertilization. Neonatal pups were either sacrificed and perfused or assigned to one of the treatment groups. Male pups were either gonadectomized or sham gonadectomized; females were all sham gonadectomized. These pups were then sacrificed and perfused on either day 26, 28 or 32 postfertilization. All brains were processed for autoradiography. The size, number and location of labeled cells within the medial preoptic area (MPOA) was determined. In general it appears that the labeled cells grow in size during the early postnatal period. These cells also migrate from the more ventral aspects of the MPOA to aggregate and form the SDN-POA. Furthermore, there is a significant decrease in the number of labeled cells by day 32 postfertilization (day 10 of postnatal life) which appears to contribute to the specific labeling of the SDN-POA of the adult animal. However, results obtained in this study from quantitative analyses do not indicate that sex or the postnatal steroid hormone environment influence the processes of growth, migration and decrease in MPOA cell number of those presumptive SDN-POA cells born specifically on day 18 of gestation and analyzed in this study. PMID- 4027685 TI - An autoradiographic analysis of the time of origin of neurons in the hypothalamus of the cat. AB - The pattern of neurogenesis of the cat hypothalamus was studied by the use of the [3H]thymidine autoradiographic method. The neurons of the cat hypothalamus are nearly all generated in a period from embryonic days E21 to E35, and in most cases the neurons in a single nucleus are generated over a much shorter period. The dominant gradient along which the cells are organized is lateral-medial (outside-in). This gradient was apparent in all nuclei except the periventricular and arcuate nuclei. Two other gradients were observed in some, but not all, nuclei. These were along the dorsoventral and the posteroanterior axis. The dorsoventral gradient was uniformly less pronounced than the lateromedial gradient. The posteroanterior gradient was most obvious in the mammillary complex. An analysis of the data suggests that the neurons of individual nuclei do not necessarily have a unique production history. This suggests that insofar as nuclear formation is concerned, factors such as the parental population generating the neurons that populate a nucleus, as well as the early neuronal interconnections, may play a more important role than the birthdates themselves. PMID- 4027686 TI - The development of cell size in the dorsal lateral geniculate nucleus of monocularly paralyzed cats. AB - Nissl profiles of cell somata in the lateral geniculate nuclei (LGN) of adult cats which had been reared from 3 to 4 weeks of age with monocular paralysis (MP) were compared to those from normally reared adult cats. In all subjects, measurements were made in 3 different regions of the binocular segments of the A and A1 laminae and in the monocular segment in both LGNs. In the cats reared with MP, reductions in average cell size of about 20%, relative to normal, were detected throughout the binocular segments of the A and A1 laminae in both LGNs whether their innervation was provided by the paralyzed or mobile eye. There were no detectable effects in the monocular segments. These results are discussed in comparison to the morphological effects of other rearing procedures, particularly strabismus and monocular deprivation. PMID- 4027687 TI - Effects of neural stimuli on paraventricular nucleus neurones. AB - The electrical activity of 122 neurones mostly located within the parvocellular components of the hypothalamic paraventricular nucleus (PVN) was recorded in urethane-anaesthetized male rats. Spontaneous activity and responses to single shock stimulation of the following sites were recorded: median eminence (ME), neurohypophysis (PIT), preoptic area (POA), nucleus accumbens (ACB), subiculum (SUB), sciatic nerve (ScN), and photic (Ph) stimulation. Stimulation of ME antidromically invaded 14% of the cells recorded, the spontaneous firing rate of these neurones was significantly slower than that of the rest of the population. The responses of the neurones identified as projecting to ME, to the above stimuli, were generally found to be in the same direction as for the whole population but the proportions of the majority responses were greater. Identified cells mainly responded with orthodromic excitation following POA, SUB, ScN, and Ph stimulation whereas ACB stimulation produced a greater proportion of inhibitiory responses. High degrees of convergence were found following afferent stimuli. The possibility that some of the neurones projecting to ME may be candidates for the corticotropin-releasing factor (CRF-) cells, is discussed. PMID- 4027689 TI - Endogenous sugar acid control of hypothalamic neuron activity and gastric acid secretion in rats. AB - The feeding related endogenous sugar acids, 2-deoxytetronic acid, 2-DTA and 3 deoxypentonic acid, 3-DPA, were investigated for their peripheral and central (hypothalamic) control of gastric acid secretion, and effects on activity of lateral hypothalamic (LHA) neurons in rats. Peripheral gastric acid secretion was not affected by either 2-DTA or 3-DPA. Slight gastric acid secretion was elicited by 3-DPA only when it was applied directly into the gastric related site of the LHA. Gastric acid secretion induced by 2-deoxy-D-glucose (2DG) was suppressed by application of 2-DTA in the LHA. 3-DPA had no effect on 2DG induced secretion. Electrophoretic application of 2-DTA significantly inhibited the activity of both gastric and non-gastric type glucose-sensitive neurons in the LHA, and 3-DPA significantly excited both types of glucose-sensitive neurons. The results agree with previous reports that 2-DTA and 3-DPA are endogenous satiety and hunger factors, respectively, and act by modulating hypothalamic control of gastric acid secretion which is mediated through gastric type and non-gastric type glucose sensitive neurons. PMID- 4027688 TI - Dissociation of subjective pain report and pain-related late positive components of cerebral evoked potentials in subjects with brain lesions. AB - Several studies have described a correlation between subjective pain report and late positive components (LPCs) of cerebral evoked potentials occurring with latencies ranging from 150 to 400 msec after the onset of painful stimuli. We report here human subjects with brain lesions who revealed very small LPCs in response to painful electrical skin stimuli applied to the finger pads even though they described strong subjective pain for the same stimuli. A decrease in pain-related LPCs was observed regardless of whether the stimuli were applied to the finger pads ipsilateral or contralateral to the brain lesions. Based on this observation, it is suggested that the pain-related LPCs may reflect neural processes which are presumably associated with information processing of painful input rather than neural processes of pain perception per se. PMID- 4027690 TI - Isolation of glomeruli from areas of bovine cerebellum and comparison of [3H]serotonin uptake. AB - A method for bulk preparation of glomerular particles from subdivisions of the bovine cerebellum is presented. This method represents a modification of that previously reported by Hajos et al. [8], which increases the yield of glomerular protein by five-fold (5.5 mg/g wet wt) without compromising structural integrity or homogeneity. In addition, it offers the advantage of allowing one to study intraregional variations in the metabolic properties of cerebellar glomeruli. [3H]Serotonin (5-HT) uptake was measured in this preparation and it was demonstrated that glomeruli possess an active high affinity mechanism for this substrate. Comparison of [3H]5-HT uptake by glomeruli isolated from the cerebellar cortices of the lateral hemispheres and vermis revealed no differences in their kinetic properties. PMID- 4027693 TI - The neural and metabolic basis of feeding. Satellite symposium of the annual meetings of the Society for Neuroscience. October 7-9, 1984. PMID- 4027692 TI - Ventral tegmental area of the rabbit brain: a developmental Golgi study. AB - The ventral tegmental area (VTA) of the rabbit mesencephalon was examined with Golgi-Cox impregnation at neonatal (days 3-21 of age) and young adult (6-12 months of age) stages of development. Neurons in the dorsal midline were small, with sparsely-branched, vertically-oriented dendrites. Neurons in the ventral midline were medium-sized, oval cells with sparse, vertically-oriented dendrites, and multipolar cells with more abundant diffusely-oriented dendrites. Neurons in the medial zone of the VTA, between the midline and the exiting III nerve fibers, were oval in shape, medium in size, and possessed vertical dendritic arborizations of greater size and extent of branching than those in the dorsal midline. Lateral neurons, found among III nerve fibers, were medium-sized and possessed dendritic trees that were specifically oriented in a vertical or horizontal plane, or were diffusely-branched with more abundant arborizations than their specifically oriented counterpart. Very small neurons with short, single branches were scattered among all regions of the VTA. The major cell types showed a similar pattern of dendritic maturation. At 3-9 days of age, the dendrites were generally short, spiny and poorly branched. From days 9-21, the branches increased in number and length, spines were lost, and these neurons rapidly approached adult size and form. The neurons of VTA appear isodendritic in form, and developed in a pattern consistent with other areas of reticular formation, suggesting that VTA may be part of the reticular core of the brain stem.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4027691 TI - New "micro push-pull" catheter system for localized perfusion of diminutive structures in brain. AB - A new double-lumen micro-catheter has been adapted for use in an integrated push pull cannula system for perfusion of brain tissue of the unrestrained animal. The catheter consists of a single strand of polyethylene tubing available in sizes with an external diameter ranging from 280-480 microns. A microcapillary pipette is drawn and inserted into each lumen of the two channels. The pipettes are then connected by polyethylene tubing to calibrated gas-tight syringes mounted on the reciprocating decks of an infusion-withdrawal pump. Since the diameter of the orifice of each lumen is equal, the simultaneous delivery and withdrawal of an osmotically balanced artificial CSF at a perfusion site is assured. In prototype experiments, the tissue exchange of 3H-norepinephrine and 14C-dopamine incorporated into the CSF perfusate was examined simultaneously at hypothalamic sites in the rat. At perfusion rates of 12.5 and 25.0 microliter/min, the mean recovery of the catecholamine neurotransmitters in terms of the radio-label residual in the perfusate ranged between 85-88 percent. The principal advantages of the new system are its flexibility, ease of sterilization and its diminutive size which enables perfusion, for the first time, of individual nuclei or fiber tracts in the brain of a laboratory animal such as the rat. Thus, a more precise delivery of a drug or other chemical agent to the site of perfusion as well as the collection of a released transmitter substance from the same anatomical locus can now be accomplished. PMID- 4027694 TI - Comparison of the metabolic and behavioral disturbances following paraventricular and ventromedial-hypothalamic lesions. AB - Lesions of the ventromedial hypothalamus (VMH) result in an obesity syndrome with several metabolic and behavioral manifestations. It has also been reported that damage to the paraventricular hypothalamus (PVH) leads to changes characteristic of obesity. However, little is known about the consequence of PVH lesions, especially in contrast to the extensive documentation of VMH lesion-induced effects. To assess the basic features of the two hypothalamic obesity syndromes, rats underwent VMH, PVH, or sham lesions and, for 15 weeks, were maintained ad lib on a series of test diets. Both lesions groups were hyperphagic and showed similar weight gains. Although both lesion groups became obese (measured by % carcass fat), VMH rats were fatter than PVH animals. Similarly, only VMH rats were hyperinsulinemic. Further tests were conducted in PVH and VMH rats restricted to control body weights. VMH, but not PVH, rats developed a persisting elevation in basal gastric acid secretion. As well, only VMH, and not PVH, animals developed an obesity when restricted to normal weights. These data indicate similarities in PVH and VMH rats maintained ad lib but experiments on restricted animals reveal fundamental differences in the two obesities and point to different etiologies. PMID- 4027696 TI - On the role of the mouth and gut in the control of saccharin and sugar intake: a reexamination of the sham-feeding preparation. AB - Adult female rats, each fitted with a gastric fistula, were tested for their "normal-feeding" (fistula closed) and "sham-feeding" (fistula open) response to saccharin and sugar solutions under a variety of conditions. When hungry, rats consumed no more of a 0.2% saccharin solution with their fistula open than they did with their fistula closed. Increasing or decreasing the saccharin concentration did not increase the amount of solution sham fed, but adding a small amount of glucose (3%) to the saccharin solution did increase the amount sham fed. Thirsty rats, unlike hungry, significantly increased their 0.2% saccharin solution intake when tested with an open fistula. When tested with a 32% glucose solution, hungry rats consumed up to six times more solution with their fistula open than with their fistula closed. The hungry rats also sham fed significantly more of the 32% glucose solution than of the 0.2% saccharin solution or 0.2% saccharin + 3% glucose solution. Sham-feeding of a 32% sucrose solution significantly elevated blood glucose levels, but blocking this effect by adding acarbose, a drug that inhibits sucrose digestion, did not reduce the amount of solution sham fed. Several possible explanations for the differential sham-feeding response to saccharin and sugar solutions are discussed. PMID- 4027695 TI - Noradrenergic innervation of the paraventricular nucleus: specific role in control of carbohydrate ingestion. AB - Acute injections of norepinephrine (NE) into the hypothalamic paraventricular nucleus (PVN) have been shown to elicit eating in satiated rats. The present report examines the effects of acute and chronic PVN infusion of NE on intake of various liquid and mixed solid diets and on selection of the pure macronutrients, carbohydrate, protein, and fat. The results demonstrate that noradrenergic stimulation of the PVN (40 nmoles of NE) reliably enhances ingestion of pure sucrose diets (liquid and solid) and also of sweet and non-sweet milk solutions. Saccharin intake, in contrast, is unaffected. In preference tests, rats injected with NE show a greater increase in consumption of sucrose cubes compared with lab chow pellets, but exhibit an equivalent preference for sweet and non-sweet carbohydrate-rich diets. Tests with the three pure macronutrients simultaneously available reveal, after NE injection, a strong and selective increase in consumption of carbohydrate, with little or no change in intake of fat and, in some cases, a suppression of protein intake. This clear preference for carbohydrate can be seen with chronic NE infusion (5 nmoles every 30 min over a 14-day period), as well as after acute NE injection (40 nmoles), and also with long-term (24-hr) as well as short-term (1-hr) food intake measurements. This and other evidence suggests that the PVN noradrenergic system may play a specific and unique role in the control of carbohydrate ingestion. PMID- 4027697 TI - Brown fat thermogenesis and its role in the development of obesity. AB - The role of brown fat thermogenesis in the development of obesity is considered from a number of perspectives. In adult rats, the impact of scapular brown fat lipectomy on carcass fat accretion was examined in three different rodent models: the Zucker lean (Fa/-) rat which is relatively resistant to obesity, the Zucker obese (fa/fa) rat which is characterized by a particularly severe form of hyperplastic obesity and the Osborne Mendel rat which remains lean on a standard pelleted diet but readily becomes obese on a palatable high fat diet. The consequences of brown fat lipectomy varied from no effect on carcass white fat accretion in Zucker Fa/- lean rats to a significant increase in adiposity in the Zucker fatty fa/fa relative to their respective sham-operated controls. The effect of the Osborne Mendel rat was intermediate between the Fa/- and the fa/fa. The results point to the importance of genetic background with respect to the impact of brown fat lipectomy on the development of white fat adiposity. In the developing Zucker rat at 2 and 8 days of age, in vivo evidence is presented to support the concept that brown fat thermogenesis is attenuated in the fatty fa/fa preobese pup. In animals of the fatty fa/fa genotype, maximum oxygen consumption in response to acute cold exposure was lower than in lean pups of the Fa/Fa genotype. Moreover, at 8 days of age, the rectal temperature of the cold-exposed fa/fa pups fell more precipitously than did that of the lean during the period of cold exposure.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4027698 TI - Impaired diet-induced thermogenesis in brown adipose tissue from rats made obese with parasagittal hypothalamic knife-cuts. AB - Two experiments were performed to determine if bilateral parasagittal hypothalamic knife-cuts (KCs), which produce long-term overeating and obesity, after biochemical indices of brown adipose tissue (BAT) reactivity to thermogenic stimuli. In the first study, responses to environmental cold were tested. Four weeks after surgery, KC rats had gained 4-5 times more weight than controls and were obese (increased Lee Obesity Index and weight of gonadal white fat). Before being sacrificed, groups of KC and control rats were exposed to 4 degrees C for 21 hr or remained at 28 degrees C. Interscapular BAT weighed 300% more in KC rats, due largely to increased white fat content. Functional indices of BAT thermogenic capacity (protein content, DNA content, cytochrome oxidase activity and mitochondrial guanosine diphosphate (GDP) binding) were normal at 28 degrees C. Exposure to 4 degrees C produced greatly enhanced responses but these were equivalent for both groups. This suggested an intact capacity for non-shivering thermogenesis in obese KC rats. In the second study, the same BAT responses were examined in other rats fed a palatable "cafeteria" diet (CAFE). One week after surgery, KC and control rats were subdivided into groups that received chow alone or chow plus four different palatable foods daily. Before sacrificing 4-5 weeks later, KC rats had gained 3-4 times more weight than controls and were obese. Interscapular BAT weighed 200-300% more in KC rats. CAFE feeding produced larger increments in all variables for KC vs. control rats. Most importantly, GDP binding was reduced in both KC groups, and significantly more so after CAFE feeding.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4027699 TI - On-line continuous measurement of blood glucose and meal pattern in free-feeding rats: the role of glucose in meal initiation. AB - Louis-Sylvestre and LeMagnen have suggested that the premeal decline in blood glucose is or reflects a signal for meal initiation in rats. In order to extend and test this hypothesis, a computer controlled system for continuously and concurrently measuring blood glucose and food intake in free-feeding rats was developed. In 18 experiments (with and without intravenous saline infusions), blood glucose declined about 12 minutes prior to meal onset. During 2-1/2 hours of observation, no decline in blood glucose and no meal occurred in 19 other experiments. In 7 experiments in which 10 percent glucose was infused IV to partially block the premeal decline (average blockade = 46.5%), the subsequent meal was significantly delayed. These results suggest that the pre-meal decline in blood glucose is not only correlated with but is also caudally related to meal onset. These studies suggest that the premeal decline in blood glucose is among the signals for meal initiation. PMID- 4027700 TI - Nutritional influences on dietary selection patterns of obese and lean Zucker rats. AB - Little is known about the behavioral, nutritional, and metabolic events that control dietary intake quality. Two experiments are described that manipulate nutritional conditions that have been hypothesized to affect dietary item choice so as to assess what effect, if any, the added factor of genetic obesity has in modifying the response to these manipulations. In the first experiment, 5 week old male obese and lean Zucker rats were fed a diet that varied in protein content (10%, 20%, or 60% casein by weight) for ten weeks. They were then allowed to select a diet from three separate macronutrient sources (casein, starch, or corn oil). Although body weights at the end of the 10 week maintenance period were markedly different, selection patterns were not influenced by pre-feeding different levels of protein. Obese rats selected a diet that was higher in fat and lower in protein than the diets composed by lean rats. In the second experiment, four groups of 7 month old obese and lean Zucker rats were given access to one of four diets that varied in protein content (5%, 10%, 15%, or 20% casein by weight). In addition, each rat was periodically given access to a 32% sucrose solution. Access to sucrose promoted increases in total caloric intake, independent of the protein content of the diet. Obese rats typically ate more calories per day than did their lean littermates. Results from these experiments suggest that food item selection is determined more by factors associated with obesity than by factors associated with dietary history. PMID- 4027701 TI - Serotonergic modulation of the feeding behavior of the medicinal leech. AB - Hungry medicinal leeches, Hirudo medicinalis, bite warm surfaces and ingest blood meals averaging 890% of their weight. Satiation lasts 12-18 months during which leeches avoid warm surfaces and will not bite. The segmental nervous system of the leech is distinguished by a population of neurons which contain serotonin (5 Hydroxytryptamine, 5-HT) at high concentrations. Some of these identified 5-HT neurons directly activate the effectors responsible for three physiological components of feeding: salivary secretion, bite-like movements and pharyngeal peristalsis. A localized warming of the lip is sufficient to initiate ingestion and synaptically excites anterior 5-HT cells into high frequency impulses or bursts. Distension of the body wall terminates ingestion and also hyperpolarizes these 5-HT neurons. Serotonin treatment produces hyperphagic behavior by the leech, while a specific pharmacological lesion of its 5-HT cell produces the anorexic behavior of satiation. This anorexia is transiently reversed by 5-HT treatment. Serotonin plays an obligatory role in the initiation and expression of leech feeding behavior by its differential modulation of central neuronal networks and peripheral glands and muscles. PMID- 4027702 TI - Superfusion of clomipramine within the ventromedial hypothalamus selectively suppresses paradoxical sleep in freely moving rats. AB - Sleep patterns were continuously recorded in rats which received during 2 hours and a half a push-pull superfusion of clomipramine at 10(-6) mol/l or 10(-8) mol/l concentrations, within the ventromedial hypothalamus. The superfusion of 10(-6) mol/l clomipramine resulted in a suppression of paradoxical sleep (PS) and a reduction of slow wave sleep (SWS), whereas lower concentrations of this drug (10(-8) mol/l) suppressed PS but did not affect SWS. In both cases, a secondary rebound of PS was observed. These findings are discussed with regard to the present knowledge of the role of the hypothalamus in sleep. PMID- 4027703 TI - AChE-positive fiber growth after hippocampal fimbria transection and peripheral nerve homogenate implantation. AB - Gelfoam treated with peripheral nerve homogenate was implanted into a site of hippocampal fimbria transection in the adult rat to assess whether the homogenate might enhance growth of AChE-positive fibers into the lesion site and whether the fiber growth might be directed to the implants. Homogenate was prepared from intact peripheral nerve and in a few cases from degenerated nerve. Some implants were encased in Silastic. Homogenate was also injected into the denervated hippocampus. The major finding was that AChE-positive fiber growth was associated with regions of high astroglial cell content in preference to the relatively hypocellular implants. No clear differences in AChE fiber sprouting into the lesion site, fiber growth into implants, or hippocampal reinnervation were noted between homogenate and saline-treated animals. PMID- 4027704 TI - Direct action of mazindol on guinea-pig ventromedial hypothalamic neurons: intracellular studies in slice preparation. AB - Neuronal responses in the ventromedial hypothalamic nucleus (VMH) to mazindol (MZD) were examined by intracellular recordings in hypothalamic slices in vitro. Bath application of MZD caused depolarization of the membrane by 8.0 +/- 3.4 mV (mean +/- S.D.) associated with an increase in the input membrane resistance (23.0 +/- 5.8%) among 20% of the cells examined. Current-voltage plots, obtained simultaneously, showed the reversal potential between -80 and -90 mV. These results indicate that MZD depolarizes VMH neurons by reducing the K+ conductance, through a mechanism similar to that of glucose, and the anorectic action of MZD can be explained by its direct effects on the VMH. PMID- 4027705 TI - Effect of vagotomy on cholinergic parameters in nuclei of rat medulla oblongata. AB - Cholinergic enzymes and muscarinic receptors in nuclei of rat medulla oblongata were examined after unilateral vagotomy to determine their association with efferent vagal neurons. Vagotomy caused an ipsilateral depletion of acetylcholinesterase from the dorsal motor nucleus of the vagus (DNV) and the nucleus ambiguus (NA). Choline acetyltransferase activity was reduced in ipsilateral DNV, nucleus tractus solitarius and rostral NA. Muscarinic receptor localization by autoradiography with [3H]quinuclidinyl benzilate (QNB) revealed marked intranuclear variations in receptor density. Vagotomy had no effect on the QNB binding pattern. Loss of cholinergic enzymes is a consistent response of motor and preganglionic autonomic neurons to axotomy. Depletion of muscarinic receptors is an additional component of axon reaction in brain stem motoneurons. Accordingly, previous studies have shown a decrease in neurotransmitter-related proteins after axotomy of motoneurons. In the present study, cholinergic enzymes were depleted from axotomized vagal neurons but receptors were not. It is concluded that muscarinic receptors in the DNV and NA are not associated with vagal efferent neurons. PMID- 4027706 TI - Anatomical evidence that neural circuits related to the subfornical organ contain angiotensin II. AB - Bidirectional connections between the subfornical organ and the hypothalamus are reviewed, and emphasis is placed on recent evidence for the presence of angiotensin II in some of these pathways. Additionally, evidence is presented suggesting that this peptide may serve as a neurotransmitter or neuroendocrine factor in the efferent projections of cell groups receiving neural inputs from the subfornical organ. It appears that angiotensin II may serve as one of the chemical messengers at each link in multi-synaptic pathways related to the subfornical organ. PMID- 4027707 TI - Electrophysiology of the subfornical organ and its hypothalamic connections--an in-vivo study in the rat. AB - The connections of the subfornical organ to a defined population of hypothalamic neurons have been explored with extracellular recording methods in the rat. Electrical stimulation in the subfornical organ has a predominantly excitatory action on a majority of oxytocin and vasopressin-secreting neurosecretory neurons in the supraoptic and paraventricular nuclei. Subfornical organ stimulation also enhances the excitability of paraventricular nucleus neurons that project to the median eminence, and to the dorsomedial medulla. These observations provide initial evidence of functional connectivity of subfornical organ neurons with other hypothalamic cells that are engaged in central regulation of pituitary secretions and autonomic activities. PMID- 4027709 TI - [Occurrence of anti-HLA antibodies in amniotic fluid]. PMID- 4027708 TI - The subfornical organ: biochemical and neuroendocrine comparisons with the hypothalamo-neurohypophysial system. AB - Biochemical, cytochemical and immunological methods were used to compare the metabolic and neuroendocrine properties of the subfornical organ (SFO) with the hypothalamo-neurohypophysial system (HNS) in the rat. The SFO resembles the HNS in that both have (a) increased label incorporation into RNA during dehydration; (b) an intense reaction for glucose-6-phosphate dehydrogenase; (c) NADPH diaphorase and the Type I pathway for hydrogen utilization from NADPH, presumably as part of the mixed-function oxidase system for the metabolism of endogenous substrates and xenobiotics; (d) immunoreactive vasopressin and oxytocin. Gel filtration of extracts of the SFO area using Sephadex G-25 chromatography resulted in immunoreactive peaks for both AVP and OT which were similar to synthetic hormones. One other fraction in the SFO extract, containing a substance(s) of higher molecular weight than AVP, was detected using the antiserum for AVP. The concentration of immunoreactive AVP in the SFO area was increased after colchicine, decreased by hypophysectomy, and unaltered by: (a) infusion (4.6 pg/min for 3 hr) or injection (1 or 6 ng) of AVP into the lateral cerebroventricle; (b) dehydration; (c) renin administered intracerebroventricularly; (d) pinealectomy; or (e) hypertension in the spontaneously hypertensive rat. In conclusion, cells in the SFO have specialized metabolic and neuroendocrine properties similar to the HNS. It can be inferred from these biochemical specializations that the SFO has metabolic and secretory activities. PMID- 4027710 TI - [Determination of the cytological stage of malignancy in breast carcinoma]. PMID- 4027712 TI - [Risk factors in ischemic heart disease and type A/B behavior]. PMID- 4027713 TI - [The effect of genetic factors on blood lipoprotein levels]. PMID- 4027711 TI - [Recording the electrical field of the heart using symbolic maps]. PMID- 4027714 TI - [Monitoring the electrocardiogram during sleep]. PMID- 4027715 TI - [Determination of the size of an irregular surface in a biological experiment using computer technics]. PMID- 4027716 TI - [Postural aberrations caused by sinusoidal galvanic stimulation of the labyrinths during various postural positions]. PMID- 4027717 TI - [Comparison of therapeutic approaches in subacute thyroiditis]. PMID- 4027718 TI - [Fibrogenicity of real mine dust and dust deposits isolated from the lungs of miners in an animal experiment]. PMID- 4027720 TI - [Changes in the shape of the thoracic wall in asthma due to the effect of loading and hypobaric conditions]. PMID- 4027719 TI - [Differences in the cholinergic effects of eserine and pilocarpine on the uvea and retina of the bovine eye]. PMID- 4027721 TI - [The composition of fatty acids and lipids in the blood of healthy people of various ages]. PMID- 4027722 TI - [Relation between a simple cytologic test and persistent disease in radiologically treated cases of carcinoma of the uterine cervix]. PMID- 4027723 TI - [Ogilvie's syndrome after cesarean section]. PMID- 4027724 TI - [Clinical aspects, diagnosis and treatment of nonspecific urethritis of chlamydial origin]. PMID- 4027725 TI - [Use of phonopulmonary signals in diagnostics in the bronchopulmonary system]. PMID- 4027726 TI - [Complications after transabdominal amniocentesis and their prevention]. PMID- 4027727 TI - [The antiarrhythmia activity of DH 1011]. PMID- 4027728 TI - [Protective reflexes of the respiratory system in conscious cats during the acute phase of oxygen deficiency]. PMID- 4027729 TI - [The importance of the biochemical examination of ascitic fluid]. PMID- 4027730 TI - [Ventricular septal defect as a complication of acute myocardial infarct]. PMID- 4027731 TI - [Determination of physiologic protein requirements in growing rats]. PMID- 4027732 TI - [Possibilities of pasture contamination with Taeniarhynchus saginatus eggs]. PMID- 4027733 TI - Performance of laying hens as affected by split time and split composition dietary regiments using ground and unground cereals. AB - A factorial experiment was conducted to study the effects on the performance of White Leghorn X Australorp laying hens of diets based on unground cereal grains, small morning and large afternoon meals, and morning and afternoon meals of different composition. From 10 to 21 weeks of age the pullets' food intake was restricted, using either a diet in which the wheat fraction (600 g/kg) was unground or a fully ground diet of similar composition. In the laying period the birds received either a diet (U) in which the limestone was granulated and most of the cereal fraction (wheat and oats or wheat and sorghum) was unground or a fully ground diet (G) of similar composition. Both laying diets were offered ad libitum (A), with 25% issued in the morning and 75% in the late afternoon (T) or as a protein concentrate (250 g/kg of total diet) in the morning and cereal/limestone fraction (750 g/kg) in the late afternoon (C). Rearing and laying performance were unaffected by rearing diet. Laying diet U resulted in a 5.2% increase in food intake and a 0.9 g increase in average egg weight compared with diet G. From 21 to 56 weeks of age, when the cereal/limestone fraction of the diet included oats (240 g/kg of total diet), diet U resulted in fewer (4.8/bird) eggs and a lower financial margin than diet G. From 56 to 80 weeks of age, when oats were replaced by sorghum, this trend was reversed (-3.5 eggs). Birds on diet C produced fewer (16.9) eggs of lower (1.5 g) average weight than birds on diet A, ate less (1.39 kg) food and had a lower financial margin.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4027734 TI - Effects of dietary protein concentration and corticosterone injections on energy and nitrogen balances and fat deposition in broiler chicks. AB - Reducing dietary protein concentration in isocaloric diets consistently decreased nitrogen and energy excretion, and increased dry matter (DM), non-protein DM (NPDM), energy retention and fatness. There were significant correlations, negative between dietary energy-to-protein (E:P) ratio and nitrogen excretion and positive between the E:P ratio and the retention of DM, NPDM and energy. Nitrogen excretion was correlated with energy excretion, and NPDM retention with energy retention. Corticosterone injections increased fatness despite significantly increasing nitrogen and energy excretion. A positive relationship was observed in corticosterone-treated birds between nitrogen excretion on the one hand and the retention of DM and NPDM on the other. Increased food intake because of a low dietary protein concentration was not evident when a sorghum-based diet was used. Moreover, corticosterone injections increased neither the food intake nor the fatness of chicks fed this diet. Decreasing the protein concentration in diets containing identical metabolisable energy (ME) levels slightly, but significantly increased apparent ME values in three out of four experiments. Corticosterone injection did not affect this variable. PMID- 4027735 TI - Heat production by the mature male turkey (Meleagris gallopavo): preliminary measurements in an automated, indirect, open-circuit multi-calorimeter system. AB - The energy metabolism of mature male turkeys (Meleagris gallopavo) was determined in a computer-controlled indirect multi-calorimeter system of which the design and operation are described. Daily heat production did not change significantly during an initial 6-d period in the calorimeter chambers. Food intake was at first sufficient to promote a rate of energy retention significantly greater than zero, but decreased to give negative energy retention on day 6; mean energy retention for the whole 6-day period was significantly greater than zero. Heat production was affected little by fasting for 72 h, although the respiratory quotient decreased to 0.72 within 48 h; the heat increment of feeding was therefore small (about 5% of metabolisable energy). Fasting heat production, scaled on metabolic body size (bodyweight in kg)0.75, was similar to that of mature male domestic fowl (Gallus domesticus). Heat production after refeeding was similar to that recorded during the 6 d before fasting. There was a pronounced circadian rhythmicity of heat production in both fed and fasted birds. PMID- 4027737 TI - Effects of exercise conditioning on semen characteristics from hyper- and hypotensive lines of turkeys. AB - Twenty-one male Broad Breasted White turkeys which had been selected for high or low blood pressure were put on an exercise regimen to determine its effect on semen quality. Eleven were from the hypertensive line and 10 from the hypotensive line. Eleven (6 hypertensive and 5 hypotensive) turkeys were placed on an exercise regime of walking (herding) about 1 mile daily for 6 weeks before the experiment began, and then for a further 6 weeks during semen collection. Semen was collected from 11 turkeys on the exercise regime and 10 nonexercised control birds which were kept in their experimental pens during the trial. Both hypertensive and exercised groups showed an improved semen colour score at the first collection period (P less than or equal to 0.09). Only the exercised group showed a significantly (P less than or equal to 0.05) better score than the control group during periods 2 and 3. The hypertensive line showed significantly higher spermatozoa count than the hypotensive line during the first collection period. There was no effect of either exercise or selection for high or low blood pressure on semen volume. PMID- 4027736 TI - Influence of food restriction during rearing on the body composition of layer strain pullets and hens. AB - The influence of two methods of food restriction during rearing on the body and liver composition of layer-type birds was investigated during and after restriction. In each of two experiments groups of birds were reared on one of three treatments: ad libitum food intake (A), time-limited food restriction (TR) or proportional food restriction (PR). All birds were fed ad libitum during the laying phase. In experiment 1, six birds from each treatment were selected at random for estimation of body and liver composition and killed at 70, 101, 162, 218 and 337 d of age. In experiment 2 four birds were selected from each treatment at 280 and 467 d of age. Body composition was predicted in experiment 2 at various times such as sexual maturity, using equations based on deuterium oxide dilution techniques. Body composition changes caused by food restriction were related to the length of restriction. Towards its end the major changes were: decreased body fat, increased total body water and increased water content of the fat-free mass for TR and PR birds compared to A birds. Some changes were not due to a reduced liveweight. Food restriction during rearing did not change body composition permanently, although predicted body fat at sexual maturity (experiment 2) was lower and protein content higher for TR and PR than for A birds. There was no demonstrable relationship between the body fat content predicted at sexual maturity and subsequent rate of lay (experiment 2). PMID- 4027738 TI - Comparison of artificial light sources and lighting programmes for laying hens on long ahemeral light cycles. AB - Three lighting treatments were given to laying hens, for which the bright and dim light of 28-h ahemeral light cycles was provided by incandescent (tungsten filament) lamps only or by combinations of tubular fluorescent or compact gas discharge lamps with incandescent lamps. There were no differences in entrainment (the proportion of eggs laid in 4, 6 or 8 h modal periods) between the three bright:dim treatments. A fourth ahemeral lighting treatment in which the dim lights were extinguished except during a designated work period (09.00 h to 12.00 h daily) was termed bright:dim:dark. Hens given the bright:dim:dark treatment showed an increased entrainment compared with the three bright:dim light treatments. There were no differences (P greater than 0.05) in egg numbers or mean egg weight between all 4 lighting treatments. Birds given the bright:dim:dark treatment tended to have a lower (P greater than 0.05) food intake compared to the three bright:dim treatments. PMID- 4027739 TI - Influence of various nesting materials on nest site selection of the domestic hen. AB - Nesting behaviour of LSL hens from a deep litter house and from a battery system was compared. Every hen was tested in one of two trial chambers containing a wire mesh floor and a nest unit with 5 nesting materials: wire mesh, perforated plastic, synthetic grass, wheat straw and oat husk. Wheat straw and oat husk were preferred as nesting materials to perforated plastic, synthetic grass and wire mesh. The results from these trials were confirmed in a deep litter house. After the nesting material, oat husk, was changed in two of 10 communal nests the hens did not accept those two nests for the trial period of two weeks and laid elsewhere. Hens of the same breed and age reared together on deep litter showed no differences in nest site selection and nesting behaviour regardless of whether they had previously been housed in a deep litter house or in cages. PMID- 4027740 TI - Quantitation of the fertilising ability of fresh compared with frozen and thawed fowl spermatozoa. AB - The fertilising abilities of freshly-diluted and frozen and thawed fowl semen were compared by inseminating a wide range (0.2 to 1600 X 10(6] of doses of spermatozoa. These data demonstrated that there was a non-linear relationship between numbers of spermatozoa and the probability of fertilisation. It was concluded that a typical fertility trial, which assesses the percentage of fertile eggs laid by groups of hens inseminated with a fixed dose of semen, was inadequate for comparing the quality of semen samples. An alternative fertility trial is described, which involves assessing the numbers of spermatozoa required to fertilize a particular percentage of eggs laid. This modified method showed that the quality of frozen and thawed semen, in terms of its fertilising ability, was reduced to 1.6% of that of fresh semen. PMID- 4027741 TI - Effect of nutrition on broiler carcase composition: influence of dietary energy content in the starter and finisher phases. AB - Three isonitrogenous starter (230 g/kg) and three finisher diets (200 g/kg) were formulated to contain 10.78, 12.78 and 14.78 MJ AME/kg and fed to 1512 male and female broilers such that there were 9 treatment combinations. Birds fed the low energy starter diet were significantly lighter (P less than 0.05) and their carcases contained proportionally less abdominal fat and total carcase fat at 24 d of age. This effect remained until 49 d of age irrespective of the finisher diet fed. The energy content of the finisher diet had no significant effect on bodyweight but the proportion of abdominal fat and total carcase fat deposited was lower for birds fed the low-energy finisher. PMID- 4027742 TI - Influence of energy intake on growth and utilisation of dietary protein and energy in germ-free and conventional chicks. AB - The effect of metabolisable energy (ME) intake on the growth and utilisation of dietary protein and energy in germ-free (GF) and conventional (CV) chicks was investigated in two experiments. In experiment 1 a high energy diet (HED, 14.8 kJ ME/g) and a marginally-adequate energy diet (AED, 11.7 kJ ME/g) were fed to the GF and CV chicks at 240 g/2 birds/10 d. In experiment 2 a diet with 13.7 kJ ME/g was fed at 118 g (low level, LL) or 128 g (high level, HL)/bird/10 d. Body weight gain, protein retention and protein retention rate were similar in GF and CV chicks on both AED and HED in the first experiment, but in the second were higher in GF than in CV chicks. The increased ME intake of the CV chicks in experiment 2 may be too small to compensate for the increased requirement. ME intake was significantly higher in the CV chicks than in the GF chicks, whereas energy retention was similar in both groups. PMID- 4027744 TI - Effect of the eumelanin restrictor Db on plumage pattern phenotypes of the domestic fowl. AB - An investigation was conducted among the progeny from crosses between Gold Pencilled Hamburgh and Partridge Wyandotte bantams into the relationship between two plumage pattern phenotypes, pencilling and autosomal barring, both of which are arrangements of eumelanin expressed on a background of phaeomelanic pigmentation. A eumelanin restricting gene Db had previously been shown to be responsible for the barred phenotype when acting in conjunction with a pattern arranging gene Ab. The pencilled phenotype had been presumed to be caused by the presence of a pencilling gene Pg. The F2 generation consisted entirely of three phenotypes: barred, pencilled and intermediary, with presumed genotypes DB/Db, db+/db+ and Db/db+ respectively, indicating that Ab and Pg are one and the same gene, for which I propose the retention of the symbol Pg. The gene action of Db when homozygous is therefore to prevent curvature, so changing pencilling into barring. PMID- 4027743 TI - Fearfulness of hens caged individually or in groups in different tiers of a battery and the effects of translocation between tiers. AB - The responses of laying hens in several fear-eliciting situations were examined. The effects of group-housing and translocation of birds between tiers upon a previously-observed relationship between fearfulness and cage level were assessed. Birds housed in the top tier showed longer durations of tonic immobility, greater avoidance of a novel rod placed in their food trough and decreased approach, activity and vocalisation when placed in a pen containing a novel object, than did their middle-tier counterparts. This relationship, which was common to birds housed either individually or socially, was disrupted by translocation between tiers. The consistently higher fear scores recorded by birds from the top tier are considered likely to reflect differences in general rather than stimulus-specific fearfulness. PMID- 4027745 TI - Effects of air velocity on convective and radiant heat transfer from domestic fowls at environmental temperatures of 20 degrees and 30 degrees C. AB - The effects of air movement upon sensible heat loss from individual birds at ambient temperatures of 20 degrees and 30 degrees C were determined by partitional calorimetry using a newly developed wind tunnel calorimeter. The relationship between area specific convective heat loss (W/m2) and air velocity (in the range 0.3 to 1.05 m/s) was described by y = 56.5 + 16.9 log x at an air temperature of 20 degrees C, but at 30 degrees C convective heat loss increased linearly with air speed (y = 11.8 + 40.1 x). At 20 degrees C sensible heat exchange (W/m2) was related to air velocity by y = 70.6 exp (0.099 x) and by y = 41.4 + 25.9 x at 30 degrees C, the proportional increase with air speed being greater at the higher temperature. The differences in the effects of air movement on convective cooling and sensible heat loss at 20 degrees and 30 degrees C reflect the thermoregulatory responses of the birds, induced by the thermal demands of the environment. PMID- 4027746 TI - Neutrophil granulocyte functions in severely burned patients. AB - Burns wound sepsis is not only the most common but also the most severe complication following extensive thermal injury. One conceivable explanation of this problem is a reduced capacity of the polymorphonuclear neutrophil leucocytes of these patients to combat the invading microbes. Fifty patients (42 male and 8 female) with deep dermal burns, covering 20-90 per cent of the total body surface area, were investigated from immediately after the injury until death or until healing of the wounds. The following functions of the neutrophil granulocytes were studied: chemotaxis and random migration utilizing a modified Boyden chamber technique, phagocytosis of Staph. aureus and IgG-coated latex particles, bactericidal capacity, e.g. killing of Staph. aureus and the neutrophil granulocyte content of: myeloperoxidase, lactoferrin, and chymotrypsin-like cationic protein. The presence of stimulators and inhibitors of the granulocyte functions was studied using gel filtration of the patient's serum on Sephacryl gel columns. Sera from all patients obtained within the first 1-3 days post-burn contained significantly increased amounts of heat-labile chemokinetic stimulating activity. Sera obtained between days 4 and 10 after injury contained significantly decreased amounts of heat-stable chemokinetic stimulating activity. Reduced chemokinetic activity was found during the third and fourth weeks following major burns (greater than or equal to 40 per cent) due to the presence of one or both heat-stable chemokinetic inhibitory activities. During the second week post-burn patients with burns larger than 40 per cent of the body surface area who showed an inhibition of chemotaxis, also had defects in phagocytosis, and often impaired bactericidal capacity concomitant with lower contents than normal of the granular enzymes. A hyaluronic acid preparation in low concentrations was found to counteract the migration inhibitory effect demonstrated in vitro in sera from patients with severe burns. Based upon these results a series of patients with severe burns and impaired functions of the neutrophil granulocytes have been treated with small amounts of this hyaluronic acid preparation subcutaneously. Very promising results have been noticed, similar to those found in vitro. PMID- 4027747 TI - Candida infection in severe burns. AB - Candida infection has become an important cause of morbidity and death in burned or immunosuppressed patients. Two patients with extensive burn complicated with Candida infection are presented, along with the risk factors, diagnostic procedures, and current methods of treatment. PMID- 4027748 TI - Bacteriological effect of cerium-flamazine cream in major burns. AB - A controlled trial of the use of either 0.05 per cent chlorhexidine for bathing burn wounds or the topical application of a cream containing cerium nitrate and silver sulphadiazine showed that the cerium-flamazine cream significantly reduced the degree of Pseudomonas aeruginosa contamination of the burn wounds of patients with burns covering more than 15 per cent of the body surface area. The adherent eschar produced by treatment with cerium-flamazine provided a satisfactory wound cover until tangential excision could be carried out. PMID- 4027749 TI - Retrospective study of reconstructive surgery of the burned hand. AB - During the 5 years 1979-1983 915 patients were admitted to the Rode Kruis Ziekenhuis, Beverwijk, for the primary treatment of burns, including 618 cases in which the hands were involved. Subsequently 105 patients required secondary surgery to 180 burned hands. This study assesses the treatment of these burned hands, the aim being to describe the problems of burned hands in relation to post burn sequelae, in general; and particularly to the reconstructive procedures employed, and to assess the final results. PMID- 4027750 TI - Early vascular grafting to prevent upper extremity necrosis after electrical burns. Commentary on indications for surgery. AB - Early vascular grafting is the only effective form of treatment for electrical burns of the wrist which are severe enough to impair blood flow to the hand. Failure to appreciate the significance of early changes in blood flow and to take prompt appropriate action may result in the irreversible loss of blood supply and subsequent amputation. This report analyses the problems encountered in six patients where the early signs of impaired blood flow were not appreciated and amputations were subsequently required. PMID- 4027751 TI - Acute renal failure in a burn patient: the advantages of continuous peritoneal dialysis. AB - An 8-year-old girl sustained 65-70 per cent body surface area burns when her clothes caught fire. Two weeks later, she developed acute renal failure (ARF) and needed dialysis therapy. The extensive, infected burn area prevented the establishment of a safe vascular access for haemodialysis. Continuous peritoneal dialysis proved to be a valid alternative form of treatment and even had advantages over haemodialysis. Large amounts of fluids, calories and electrolytes could be administered via the peritoneal route. This facilitated the treatment of the catabolic state of the uraemic burn patient and served to correct the electrolyte losses via the skin. Peritoneal dialysis is a valuable adjunct to the treatment of acute renal failure in burn patients who need renal replacement therapy. PMID- 4027753 TI - Epidemiology of flame burn injuries. PMID- 4027752 TI - Resurfacing of the severely burned hand with a radial forearm flap. AB - The distally based island radial forearm flap has been used successfully on three occasions to resurface the severely burned hand as a single-stage procedure, in patients unsuitable for a multi-stage operation. PMID- 4027754 TI - Cytokinetics of a human neuroblastoma cell line following treatment with dianhydrogalactitol. AB - Studies were carried out on the effect of dianhydrogalactitol on a human neuroblastoma cell line in culture. The drug was cytotoxic at concentrations of 5 micrograms/ml and 10 micrograms/ml for 1 hour, but not at 1 microgram/ml. Flow cytometry of DNA showed that cell kill was preceded by a transient accumulation of cells in early S at 10 hours, and in late S at 36 hours. Smaller increases in the percent of cells in S phase were seen after treatment with 1 microgram/ml, without cell kill. It may be concluded that dianhydrogalactitol causes an S-phase block, followed by death of cells in late S at concentrations above 5 micrograms/ml. PMID- 4027755 TI - Ferritin in neuroblastoma. Impact of tumor load and blood transfusions. AB - Serial serum ferritin (SF) levels were measured in 36 patients with neuroblastoma seen at Memorial Sloan-Kettering Cancer Center (MSKCC) between January 1981 and December 1982. The significance of the associations among SF, stage and extent of disease, number of blood transfusions, liver function, serum iron (Fe), total iron-binding capacity (TIBC), and transferrin saturation was investigated. Although a dominant statistical correlation was found between SF and number of blood transfusions, the results suggest that amount of disease contributes to increasing SF levels. Serum ferritin levels increased on average in a linear fashion with number of blood transfusions in patients free of disease or with minimal disease. In patients with bulky disease, this increase was exponential (p value less than 0.01). Application of a reverse hemolytic plaque assay to the analysis of ferritin secretion by cells demonstrates that tumor cells do secrete ferritin in vitro. PMID- 4027757 TI - [Increase in mortality in Poland in recent years]. PMID- 4027756 TI - [Health and social justice]. PMID- 4027759 TI - [Integration of medical strategies in a specialized department]. PMID- 4027758 TI - [The health system in industrial countries: long-term perspectives]. PMID- 4027760 TI - [Formal approach to the clinical decision]. PMID- 4027761 TI - [The fundamental unit of information of the computerized medical record: the Standardized Medical Transaction]. PMID- 4027762 TI - Factors affecting leak around tracheal tubes in children. AB - This study determined which variables affected endotracheal tube "leak" pressures in 80 surgical patients, two weeks to 11 years of age, intubated with uncuffed tracheal tubes. We defined "leak" pressure as the inspiratory pressure needed to cause an audible escape of gas around the endotracheal tube. "Leak" pressure was measured after varying either head position, tracheal tube depth within the trachea, fresh gas flow rate, or degree of neuromuscular block. "Leak" pressure increased progressively from 16.9 +/- 1.3 cmH2O with complete patient paralysis to 30.6 +/- 1.4 cmH2O following 100 per cent recovery of neuromuscular function. Turning the head from a neutral position to one side increased "leak" pressure from 14.7 +/- 1.7 cmH2O to 24.4 +/- 2.5 cmH2O. Varying tracheal tube depth or fresh gas flow rate produced no significant change in "leak" pressure. Thus, there may be marked variability in "leak" pressure, depending on head position and degree of neuromuscular blockade. Keeping the patient fully paralyzed with the head in a neutral position provides a reliable and consistent method for measuring "leak" pressures. PMID- 4027763 TI - Lidocaine attenuates the intraocular pressure response to rapid intubation in children. AB - To determine the effect of intravenous lidocaine on the intraocular pressure (IOP) response to laryngoscopy and intubation, twenty unpremedicated children, ages one to ten years were studied. After administration of either intravenous sterile water (control) (n = 10) or preservative-free lidocaine (1.5 mg X kg-1) (n = 10), anaesthesia was induced with pancuronium (0.15 mg X kg-1), thiopentone (5 mg X kg-1), and atropine (0.02 mg X kg-1), and maintained with halothane, nitrous oxide and oxygen. The trachea was intubated one minute after administration of thiopentone. IOP (measured by applanation tonometry), heart rate, and systolic blood pressure were measured at the time of loss of the eyelid reflex (time 0), immediately after endotracheal intubation, and each minute thereafter for five minutes. In the control group, IOP increased (27 per cent) significantly after intubation (p less than 0.05), whereas in the lidocaine group, IOP did not increase (9.8 per cent) significantly after intubation. IOP decreased below time 0 values within three minutes after loss of the eyelid reflex in the lidocaine group (p less than 0.05). At each measurement (except time 0), IOP was significantly greater in the control group than in the lidocaine group (p less than 0.05). Heart rate and systolic blood pressure did not increase significantly in either group after intubation. We conclude that intravenous lidocaine (1.5 mg X kg-1) significantly attenuates the IOP response to laryngoscopy and intubation in children anaesthetized with pancuronium, thiopentone, and atropine. PMID- 4027765 TI - Thrombolytic therapy. PMID- 4027764 TI - Plasma levels of vitamin E and lipoperoxide during paediatric anaesthesia. AB - We measured plasma levels of vitamin E (total tocopherol) and lipoperoxide in seventeen neonates (less than 10 days), twenty infants (1-12 months) and ten children (1-5 years) during anaesthesia. The seventeen neonates were randomly divided into two groups; seven who received 30 mg X kg-1 of alpha-tocopheryl acetate intramuscularly before anaesthesia and ten who did not. The 20 infants were divided into three groups: Group 1: eight infants who did not receive vitamin E; Group 2: six who received 30 mg X kg-1 of alpha-tocopheryl acetate orally for three days before anaesthesia; Group 3: six who received 30 mg X kg-1 of alpha-tocopheryl acetate intramuscularly three hours before anaesthesia. In the neonates who did not receive alpha-tocopheryl acetate, plasma vitamin E and lipoperoxide levels were unchanged following surgery. In Group 1 infants, plasma vitamin E levels decreased (p less than 0.05) and plasma lipoperoxide levels increased (p less than 0.05). In both neonates who received vitamin E and Group 3 infants the mean plasma vitamin E levels increased significantly (p less than 0.05) following surgery. In Group 2 infants, the levels of plasma vitamin E before surgery were high, as compared to the other groups: however, plasma vitamin E levels decreased following surgery. In the children, the plasma vitamin E levels were unchanged, while the plasma lipoperoxide levels decreased significantly (p less than 0.05) during anaesthesia. It is suggested from our studies that plasma vitamin E levels decrease and plasma lipoperoxide levels increase during anaesthesia and surgery in infants; however, those levels are unchanged in neonates. PMID- 4027766 TI - Controversies in pain relief in anaesthesia. Calgary, Alberta, November 17, 1984. PMID- 4027768 TI - Bilateral hydrothorax and hydromediastinum after a subclavian line insertion. AB - A 28-year-old male patient developed bilateral hydrothorax due to extravasation of fluid into the mediastinum from a subclavian line. The injection of radio opaque dye through the central venous cannula confirmed spillage into the mediastinum. There was no direct communication between the central venous cannula and the pleural cavities. The hydrothorax appeared to develop as a result of a shift of fluid from the mediastinum into the pleural cavities due to pressure differences in the two compartments. Bilateral chest tubes were inserted, the subclavian cannula was removed and the patient made a good recovery. PMID- 4027769 TI - Acute epiglottitis in a 79-year-old man. AB - A case of acute epiglottitis in a 79-year-old man is presented describing the airway and anaesthetic management. Early reports of adult epiglottitis advocated observation or tracheostomy for airway management. Recent reports stress early endotracheal intubation. Unlike the paediatric age group adults may present with differing degrees of airway obstruction, epiglottic abscess, and with a more diverse set of medical problems. This can make airway management more variable than in children. A discussion of airway management in adult epiglottitis is presented. PMID- 4027770 TI - Caesarean section for twins in a patient with myotonic dystrophy. AB - The management of a patient with myotonic dystrophy undergoing Caesarean section for delivery of twins in breech position is reported. Anaesthetic management must reflect the multi-system nature of the disease in addition to the implications of pregnancy. Known triggers of myotonic crisis (succinylcholine, shivering) must be avoided. Attention to respiratory reserve is necessary in view of the restrictive defect this disease can impose. Cardiomyopathy and conduction system disturbances may be features. Upper gastrointestinal incoordination can superimpose the added risk of aspiration on the pregnant myotonic. Ineffective uterine contraction can cause vigorous post partum haemorrhage. Endocrine disturbances, especially diabetes mellitis, may be present. There may be increased sensitivity to sedative and narcotic agents. The newborn myotonic will need the expertise of neonatal care. PMID- 4027771 TI - Anisocoria after anaesthesia. AB - Unequal pupil size following anaesthesia is an unsettling finding, suggestive of acute, perioperative intracranial pathology. We report here an unusual cause of anisocoria after anaesthesia: unintended entrance of phenylephrine nasal vasoconstrictor solution into the eye. PMID- 4027767 TI - Anaesthetic considerations for separation of omphalo-ischiopagus tripus twins. AB - Anaesthesia for the separation of conjoined twins requires a multi-disciplinary team approach. We describe the anaesthetic management of a single-stage separation of 2 1/2-year-old omphalo-ischiopagus tripus conjoined twins. The successful 17 1/2-hour operation was conducted by five anaesthetists and 38 surgeons and nurses. Two major problems were encountered: massive blood loss in both twins (requiring transfusions of more than five and seven times their blood volumes) and a transient decrease in core temperatures after separation. PMID- 4027775 TI - Chromosome banding in salmonid fish: nucleolar organizer regions in Salmo and Salvelinus. AB - Chromosome banding patterns obtained by silver staining (Ag-NORs) were analyzed in three species of Salmo (rainbow, brown trout, and Atlantic salmon) and three species of Salvelinus (brook trout, lake trout, and arctic char). In rainbow trout and Atlantic salmon the Ag-NORs were found at the secondary constrictions of a single chromosome pair, while in brown trout the Ag-NORs were found on the short arms of one or two of the two longest subtelocentric or acrocentric chromosome pairs. The location of the Ag-NORs was multichromosomal in the three Salvelinus species, occurring on one or both members of four to six different chromosome pairs in different individuals. The Ag-NOR sites were on the short arms of some acrocentric pairs and at the telomeres of other acrocentric pairs and one or two metacentric pairs. Chromomycin A3 positive bands were found at the same sites as the Ag-NORs in all species. In the species with multichromosomal location of Ag-NORs, polymorphisms in the size and location of the NORs were extremely common, so that almost every individual fish had a different pattern of Ag-NOR sites. PMID- 4027772 TI - Heart block after intravenous lidocaine in an infant. AB - A 14-day-old infant received intravenous lidocaine (2 mg X kg-1) at the conclusion of cataract surgery to prevent coughing from tracheal tube stimulation. Within 30 seconds the infant developed high-grade AV heart block and a ventricular rate of 40. Following brief resuscitation efforts, the patient had a normal cardiac rhythm, blood pressure and respiratory pattern. Intravenous lidocaine may be followed by major disturbances in cardiac rhythm and rate. Cautious titration of small doses should decrease the potential for adverse effects. PMID- 4027773 TI - A clinical sign to predict difficult tracheal intubation: a prospective study. AB - It has been suggested that the size of the base of the tongue is an important factor determining the degree of difficulty of direct laryngoscopy. A relatively simple grading system which involves preoperative ability to visualize the faucial pillars, soft palate and base of uvula was designed as a means of predicting the degree of difficulty in laryngeal exposure. The system was evaluated in 210 patients. The degree of difficulty in visualizing these three structures was an accurate predictor of difficulty with direct laryngoscopy (p less than 0.001). PMID- 4027774 TI - Symmetrical and asymmetrical sexual isolation among laboratory strains of Drosophila ananassae. AB - Male-choice experiments using five isofemale lines of Drosophila ananassae originating from different localities were performed to study sexual isolation within the species. In most of the crosses homogamic matings outnumber heterogamic ones, and deviation from randomness is statistically significant in 11 of 20 crosses. This provides evidence for positive assortative mating within D. ananassae. Isolation indices range from -0.057 to 0.555. Eleven positive isolation indices are significantly greater than zero. Both types of sexual isolation, symmetrical and asymmetrical, have been observed among different strains. Thus the present results clearly indicate that the laboratory strains of D. ananassae have developed behavioural reproductive isolation as a result of genetic divergence. PMID- 4027776 TI - The meiotic and mitotic chromosomes of picture-winged Hawaiian Drosophila species. I. Drosophila grimshawi and D. cyrtoloma. AB - The mitotic and meiotic chromosomes of Drosophila grimshawi and Drosophila cyrtoloma, species of the picture-wing group of Hawaiian Drosophilidae, are described. The "primitive" Drosophila karyotype of five pairs of rods and one pair of dots, found in grimshawi, is compared with the karyotype for cyrtoloma, which consists of five pairs of V-shaped and one pair of J-shaped chromosomes. Cytological material was prepared by an acetoorcein technique and by C-, G-, and N-banding methods. The rod-shaped chromosomes of grimshawi contained approximately 45% heterochromatin as determined by differential staining with Giemsa. Each chromosome of cyrtoloma consists of a euchromatic arm and a heterochromatic arm; the total heterochromatin of the diploid set averaged between 55 and 60%. These measurements approximate the amounts of satellite DNA reported for these two species. Prophase and metaphase figures from both meiotic and mitotic divisions are shown. PMID- 4027777 TI - Cytogenetic analysis of 34 early stage bovine embryos from superovulated Hereford donors. AB - One hundred and thirty-four bovine embryos were collected from 17 superovulated Hereford cows and processed for metaphase chromosome spreads. Mitotic figures were obtained from 54 embryos (40%), but only 34 embryos (25%) provided analyzable chromosomes spreads. Thirty embryos were 2n = 60, one was a possible 2n/4n mosaic and three were hypodiploid. The hypodiploid cases and the 2n/4n mosaic could be due to technical artifacts. PMID- 4027779 TI - Salmonellae and pollution indicator bacteria in municipal and food processing effluents and the Cornwallis River. AB - A study was conducted to determine the incidence of fecal coliforms, fecal streptococci, Aeromonas hydrophilia, and Salmonella spp. in the waste discharges of seven sewage treatment plants, four fruit and vegetable canneries, a meat packing plant, a poultry processing plant, and a potato processing plant located along the Cornwallis River in Nova Scotia, Canada. Surface water samples were also collected from 13 locations in the river to assess the impact of these waste discharges on the receiving water quality. The results showed that the final effluents from most of the sewage treatment and processing plants were of very poor bacteriological quality, with the number of indicator bacteria comparable with those found in raw sewage. Salmonellae were isolated from the effluents of the meat and poultry plants and five of the seven sewage treatment plants surveyed. No salmonellae were detected in the effluents of the fruit and vegetable canneries. The impact of the discharge of untreated municipal and food processing wastes on the Cornwallis River water quality was evidenced by the recovery from river water of five Salmonella serotypes, and the high fecal coliform counts which exceeded recommended limit for bathing and shellfish harvesting. PMID- 4027780 TI - The broken hip. PMID- 4027778 TI - Chemical and enzymatic variation in the cell walls of pathogenic Candida species. AB - Cell walls, isolated from seven pathogenic species of Candida, were lipid extracted and fractionated by treatment with ethylenediamine or enzymatically hydrolyzed using chitinase and laminarinase. Two different chitinase preparations were used, one from Streptomyces sp. which had some beta-1,3-glucanase activity, and another from Serratia marcescens which did not have glucanase activity. Laminarinase was a commercial preparation. The monosaccharide constituents of whole cell walls and the fractions derived from them were determined qualitatively and quantitatively by gas-liquid chromatography of the products of a mild acid hydrolysis and by the phenol - sulfuric acid assay of the products of a stronger acid hydrolysis. The monomeric constituents of the enzymatic hydrolyses were analyzed using gas-liquid chromatography. Approximately 50% of all walls was soluble in ethylenediamine. Glucose and mannose were the only monosaccharides found in all of the fractions derived from ethylenediamine extraction examined. Similarities among the strains, based upon relative amounts of glucose and mannose, were more apparent than differences, but statistical analyses of the data revealed a general trend of decreasing similarity in the following order, C. albicans and C. stellatoidea, C. tropicalis and C. parapsilosis, and C. pseudotropicalis, C. guilliermondii, and C. krusei. In the enzymatic assays, mannose and glucose were released by laminarinase, whereas glucose and N-acetyl-D-glucosamine or N-acetyl-D-glucosamine alone were released by the chitinases. These assays supported the trend in relationships cited above, with the data being somewhat more definitive. PMID- 4027781 TI - Penile dressing after hypospadias surgery. PMID- 4027782 TI - Hip pinning, past and present: Richards' compression-screw fixation versus Ender's nailing. AB - The authors trace the operative treatment of intertrochanteric hip fractures from the earliest to the most modern methods and describe how current fixation devices evolved. The operative and perioperative morbidity, mortality and outcome in 57 patients treated by Ender's nailing were compared with those of 51 patients treated by Richards' compression-screw fixation. Results were comparable to those found in an extensive review of the literature except for a higher mortality in the group managed by Ender's nailing. The authors conclude that both methods of treatment are acceptable and that the ultimate choice of fixation device should be based on the surgeon's experience tailored to the individual patient's needs. PMID- 4027783 TI - Fate of claudicants after femoropopliteal vein bypass: prospective, long-term follow-up of 100 patients. AB - Femoropopliteal bypass grafting for claudication is a controversial procedure. One hundred consecutive patients so treated were analysed for vein-graft patency, subsequent operation and survival. Initial success, treatment of incipient graft failure and attrition from death were the three critical factors influencing long term benefit. Cumulative graft patency, after revision when necessary, was 89%, 86% and 78% at 2, 5 and 10 years respectively. In assessing the real benefit of surgery in this group, it is important to consider the effect of late deaths, as the life expectancy of these patients is so often shortened by related disease; the "cumulative palliation" (patient alive and graft patent) was 82%, 67% and 28% at the same time intervals. The concept of cumulative palliation sets a high standard in assessing results of vascular surgery, adding important information to the usual graft patency rates that ignore the effect of death. These results suggest a place for femoropopliteal vein bypass grafting in selected claudicants. PMID- 4027786 TI - Current use of sphincter-saving excision in the radical treatment of rectal cancer. AB - The author examines the recent increased use of sphincter-saving forms of excision to treat carcinomas of the middle third and upper part of the lower third of the rectum. This trend has been due chiefly to technical innovations- especially the introduction of the circular stapler, which has extended the downward reach of low anterior resection--and the willingness to accept a distal margin of clearance in resections of 2.0 to 2.5 cm instead of 4 to 5 cm. Published data show that these innovations are associated with a low operative mortality and that satisfactory anorectal function can be retained. Insufficient length of follow-up, however, has made it impossible so far to calculate valid long-term survival rates and the high incidence of local recurrence in some reports has been disturbing. PMID- 4027784 TI - Statistical prediction of cardiac risk in patients who undergo vascular surgery. AB - Since August 1982, an extensive computerized data base has been developed on all patients admitted to the Division of Vascular Surgery at the Ottawa Civic Hospital. For each patient, 180 variables are recorded, including information about preoperative risk factors and postoperative complications. Since cardiac complications are a major cause of mortality and morbidity, the data file has been used to study postoperative cardiac complications in patients who undergo arterial reconstructive operations. Between August 1982 and December 1983, 353 artery repairs were performed, excluding ruptured aneurysms. Cardiac complications developed following surgery in 56 patients. Risk factors were initially studied using contingency table analysis. Four of these factors were found to be significant: electrocardiographic evidence of previous myocardial infarction (p = 0.0003), nonspecific ST-segment changes (p = 0.0007), New York Heart Association classification of symptoms (p = 0.0003) and age (p = 0.01). A further statistical study was based upon multiple logistic regression. The authors believe that the identification of a high-risk group, using these criteria, is helpful in selecting patients for intensive preoperative investigation, including coronary arteriography. PMID- 4027785 TI - Intraoperative bacterial contamination of vascular grafts: a prospective study. AB - The establishment of graft infection depends on host response, an appropriate field and bacterial contamination. Intraoperative bacterial contamination of prosthetic graft material was studied prospectively in 77 patients. Vascular reconstruction was indicated for abdominal aortic aneurysm (15%), claudication (42%), rest pain (25%) and ulceration or gangrene (18%). In 78% of cases the procedure was elective. Staphylococcus epidermidis was isolated in 80% of cultures; mixed flora were more frequent in patients with rest pain (60%) and ulceration or gangrene (45%) than in those with aneurysms (22%) or claudication (16%). Grafts became contaminated in 56% of cases using standard techniques; this was lowered to 35% when the surgeon changed gloves before preclotting the graft. There was no significant difference with respect to the surgeon who performed the operation, the indication for operation, primary versus secondary repair or the use of skin barriers. One patient (1.3%) had an established graft infection. It is concluded that the incidence of contamination is high but may be decreased by glove changing. PMID- 4027787 TI - Adjuvant chemotherapy in colorectal cancer. AB - The current status of adjuvant therapy for colorectal cancer is reviewed using examples from selected, recently completed, randomized, prospective, clinical trials. Although adjuvant systemic therapy is of limited therapeutic efficacy in cancer of the colon, there have been examples of beneficial effects in specific patient subsets. The rationale and current status of adjuvant portal vein hepatic perfusion suggest that it represents a potentially promising approach that must be evaluated in a large prospective randomized study. Finally, the value of adjuvant radiotherapy and chemotherapy for carcinoma of the rectum is assessed. Although one study has demonstrated increased disease-free survival for patients receiving a combination of chemotherapy and radiotherapy, the small numbers in the study preclude any definitive conclusions. The current National Surgical Adjuvant Breast Project, rectal protocol R-01, the largest rectal cancer study with a concomitant "untreated" control, is reviewed and discussed. PMID- 4027788 TI - What is appropriate follow-up for the patient with colorectal cancer? AB - Overall recurrence rates after curative resection for colorectal cancer average 30%. The value of intensive follow-up protocols is assessed from a review of the literature, which reveals that recurrent colorectal cancer can be detected at an earlier stage (average 3 months) and that repeat resection rates for cure can be increased (twofold or more) by intensive follow-up. Despite this, no improvement in survival has been documented. As nonsurgical modalities of therapy for recurrence become further refined, earlier detection of recurrent tumour will become increasingly important. An intensive follow-up regimen is therefore proposed, based on a knowledge of the patterns and timing of recurrence, the relative merits of the investigational modalities available and the assumption that at some point earliest detection and subsequent therapy will improve survival. PMID- 4027789 TI - Percutaneous removal of upper urinary tract calculi: experience with ultrasonic lithotripsy. AB - From October 1983 to March 1985, the authors removed upper urinary tract calculi percutaneously in 102 patients. In 89 patients, stones required disruption with an ultrasonic lithotriptor before removal. Fifty-two patients had a stone in the renal pelvis and 20 had calyceal stones only; 21 had stones at both sites and 9 had a stone in the upper ureter. Complete removal of all stone material was achieved in 67 of 68 patients with a solitary calculus, in 13 of 26 with multiple calculi and in 6 of 8 with ureteric calculi. Complications were minimal; three patients had pulmonary edema postoperatively as a result of excessive absorption of irrigating fluid, and one patient sustained a perforation of the descending colon. The mean postoperative hospital stay was 6.8 days and patients were able to return to work a few days after their discharge from hospital. Percutaneous stone removal is a safe and effective procedure and is the surgical procedure of choice for the removal of upper urinary tract calculi. PMID- 4027790 TI - Pseudomembranous colitis and wound infection following perioperative use of multiple antibiotics. AB - The prophylactic use of antibiotics in elective surgery of the colon is accepted practice, but it has inherent risks. The authors report the case of a 70-year-old woman who had wound infection and severe, relapsing pseudomembranous colitis due to Clostridium difficile after a short course of antibiotics given orally and parenterally at the time of elective resection of the colon. Perioperatively, she received erythromycin base and neomycin orally, plus netilmicin and metronidazole intravenously. Although the concomitant administration of parenteral antibiotics may enhance the benefit of antibiotics given orally before operation, this does not entirely prevent wound infection. Until the relation between the number of drugs and risk of antibiotic-associated colitis is more clearly defined, caution should be exercised in the use of multiple antibiotics in elective colonic surgery. PMID- 4027791 TI - Simplified insertion of the Port-A-Cath implantable drug-delivery system. AB - The increasing frequency with which antineoplastic drugs are being used demands improved vascular access for their administration. Venous access through implantable catheters facilitates treatment when veins are no longer available. Totally implantable catheters of the Port-A-Cath type are preferred because they give better performance and cosmetic results, and are more convenient for the patients. The flexibility of these catheters makes their introduction difficult. The author describes a simplified technique, using a commercially available introducer that has been used satisfactorily in thousands of pacemaker implantations. The author has used this technique routinely with a 50% decrease in operative and fluoroscopy time and without complications. PMID- 4027792 TI - Preoperative Gelfoam embolization of supratentorial meningiomas. AB - Intracranial meningiomas are often highly vascular and a successful outcome depends upon surgical resection. Preoperative embolization of supratentorial meningiomas, which have a major blood supply from the external carotid artery, has been advocated to reduce intraoperative bleeding and thus facilitate surgical extirpation. The authors carried out transfemoral, Gelfoam embolization preoperatively in eight patients with supratentorial meningiomas. In seven of the cases, post-embolization, contrast-enhanced, computerized tomography was carried out. Areas of low-density tumour necrosis were identified in five. In three of the eight patients, post-embolization angiography demonstrated elimination of the tumour blush and in the other five, the blush was reduced in intensity. Histologic evidence of tumour embolization was identified in each case to a varying degree. Preoperative embolization resulted in an identifiable radiologic change in the majority of these tumours, but the authors could not determine, in this small series, whether intraoperative bleeding was reduced. PMID- 4027793 TI - Benign cystic teratoma of the ovary: a 6-year review. AB - Benign cystic teratoma of the ovary was diagnosed histologically in 118 patients over 6 years at the Sir Mortimer B. Davis-Jewish General Hospital in Montreal. The charts were reviewed with respect to population distribution, symptomatology, diagnostic procedures and treatment. Of the 118 patients, 85.6% were younger than 40 years. Only 3.4% had documented recurrence and 6.8% were pregnant. Roentgenograms of the pelvis revealed calcification in 64.1% of cases. Ultrasonography of the pelvis failed to make the diagnosis in 19.4%. The majority of patients had a Pfannenstiel incision (78.8%) and underwent oophorectomy (55.3%). In half the patients the contralateral ovary was only palpated. PMID- 4027794 TI - Empyema: analysis of treatment techniques. AB - Empyema is associated with a high mortality. To study the factors responsible for the failure of treatment, the authors reviewed 90 cases of nontuberculous thoracic empyema seen at the University of Western Ontario in London, between 1970 and 1980. The most common causes of empyema were bronchopulmonary infections (63%), complications of pulmonary surgery (14%) and secondary infections of hydrothoraces or hemothoraces (13%). In 51 patients (57%) the condition was acquired in hospital or was related to previous medical therapy. Nine cases were recognized only at autopsy. The treatment of empyema was assessed in 81 patients, who received an average of 2.2 antibiotics during the course of treatment. Five patients received antibiotics as the only therapy; one died. Seventy-two patients were treated by surgical drainage; 35 (49%) were cured and 18 (25%) subsequently died. Twelve of 18 decortication procedures were successful including 4 performed as a primary procedure and 8 as a secondary procedure. Five of seven patients who underwent thoracoplasty were cured. The overall mortality in the series was 23%. Prevention and early recognition of empyema may reduce the mortality. Patients who do not improve promptly with surgical drainage may benefit from early decortication. PMID- 4027795 TI - Campylobacter and endovascular lesions. AB - Because of the gaps in our knowledge of the epidemiology and pathogenesis of Campylobacter infections, particularly the propensity of Campylobacter fetus ssp fetus to infect vascular endothelium, the authors describe the case of a 56-year old woman with C. fetus ssp fetus infection of an aortic aneurysm. She recovered after a one-stage surgical repair and antibiotic therapy with erythromycin. The organism was cultured from samples of the stool and tissue obtained at operation. It was identified from its typical characteristics: morphology, microaerophilic, able to grow at 22 degrees C and 37 degrees C but not at 42 degrees C, catalase and oxidase positive and resistant to nalidixic acid but susceptible to cephalothin. PMID- 4027796 TI - Why case reports? PMID- 4027798 TI - Wife-beating: how to handle the assailant. PMID- 4027797 TI - "Do not resuscitate". PMID- 4027799 TI - Prevention of alcohol withdrawal seizures. PMID- 4027800 TI - Fragile X: a symptom of the disease? PMID- 4027801 TI - Deaths caused by faulty cribs. PMID- 4027802 TI - Radiation oncology in Canada. PMID- 4027803 TI - Language and survival. PMID- 4027806 TI - Medical education reduces inappropriate use of cimetidine in a teaching hospital. AB - Before and after an education program to improve appropriate prescribing of cimetidine in an 810-bed teaching hospital, all new prescriptions written during a 4-week period were investigated, and information was obtained as to the indications for use, the dosage and concurrent drug therapy. The prescriptions were judged appropriate or inappropriate according to indications for cimetidine approved by the Department of National Health and Welfare's Health Protection Branch. After the program 63% of the prescriptions were deemed appropriate, compared with 40% before the program. The proportion of patients at risk of drug interactions, however, remained virtually unchanged. The results suggest that medical education can reduce the inappropriate use of cimetidine in teaching hospitals. PMID- 4027804 TI - Musculoskeletal chest wall pain. AB - The musculoskeletal structures of the thoracic wall and the neck are a relatively common source of chest pain. Pain arising from these structures is often mistaken for angina pectoris, pleurisy or other serious disorders. In this article the clinical features, pathogenesis and management of the various musculoskeletal chest wall disorders are discussed. The more common causes are costochondritis, traumatic muscle pain, trauma to the chest wall, "fibrositis" syndrome, referred pain, psychogenic regional pain syndrome, and arthritis involving articulations of the sternum, ribs and thoracic spine. Careful analysis of the history, physical findings and results of investigation is essential for precise diagnosis and effective treatment. PMID- 4027805 TI - Carbon monoxide poisoning. AB - Carbon monoxide poisoning is a significant cause of illness and death. Its protean symptoms probably lead to a gross underestimation of its true incidence. Low levels of carbon monoxide aggravate chronic cardiopulmonary problems, and high levels are associated with cardiac arrhythmias and cerebral edema. Patients who survive acute poisoning are at risk of delayed neurologic sequelae. The measurement of carboxyhemoglobin levels does not reveal the tissue levels of carbon monoxide but is useful in determining therapy. Treatment includes the monitoring and management of cardiac arrhythmias and oxygenation. Hyperbaric oxygenation is beneficial, but there are currently no definite criteria for its use. PMID- 4027807 TI - Eye injuries associated with war games. AB - War games, an outdoor activity combining recreation, military maneuvers and fantasy, are becoming a popular recreational sport. Increasing numbers of players are suffering eye injuries. In the last year 26 cases of serious eye injuries were reported to Canadian ophthalmologists; in 15 eyes vision was reduced to 6/24 or less. Although eyeguards are provided, all the injuries had occurred when the participants were not wearing them. Methods of preventing eye injuries in war games are discussed. PMID- 4027808 TI - Correlation between clinical and autopsy diagnoses in a community hospital. AB - Forty-six consecutive autopsies performed in 1 year on patients who died in a 120 bed urban community hospital were analysed with respect to clinical-pathological correlation. The mean age of the patients was 71 years. Errors in clinical diagnosis were assigned to one of four classes: class I, a missed major diagnosis, the detection of which before death would probably have changed management and resulted in longer survival or possible cure; class II, a major missed diagnosis that, if detected before death, would probably not have altered management; and classes III and IV, minor missed diagnoses. Six (13%) class I and 10 (22%) class II errors were found, as well as a number of class III and IV errors. Suggestions are made regarding the use of such data in audit procedures. PMID- 4027809 TI - Sudden death associated with compression of pulmonary arteries in sarcoidosis. PMID- 4027810 TI - Restless leg syndrome relieved by cessation of smoking. PMID- 4027811 TI - Psychosis due to transdermally administered scopolamine. PMID- 4027812 TI - Diarrhea update. PMID- 4027813 TI - Outbreak of Shigella flexneri 1 infection in British Columbia. PMID- 4027814 TI - Oral contraceptives, 1985: a synopsis. PMID- 4027815 TI - Health care in Uganda: restoring a shattered system. PMID- 4027816 TI - American family physicians battle HMOs. PMID- 4027817 TI - Medicine versus crime. PMID- 4027818 TI - Dr. Lucid's word rounds: introducing IMRAD. PMID- 4027819 TI - CMA policy summary on smoking and health. PMID- 4027820 TI - Drug management of cancer pain. PMID- 4027821 TI - Possible origin of human AIDS. PMID- 4027822 TI - Limited-protein diet in chronic renal disease. PMID- 4027823 TI - Graduates of foreign medical schools: false hope. PMID- 4027825 TI - Restraints and the elderly. PMID- 4027824 TI - Danger of three-wheeled recreational vehicles. PMID- 4027826 TI - "The Silent Scream": setting the record straight. PMID- 4027827 TI - Sex ratio of offspring of patients with prostatic cancer. AB - We have examined the fertility of 354 patients with prostatic cancer and 597 controls who had married at least once and formed part of a population-based case control study in Alberta. Considering offspring of both sexes, the mean fertility of the patients was 3.17, not significantly different from the mean of 3.11 for the controls. However, the sex ratios were significantly different, 56.5% of the patients' offspring being sons, compared with 50.1% of the controls' offspring. The difference in sex ratio persisted after adjustment for ethnic group, level of education and age at first marriage, which were found to be risk factors for prostatic cancer. PMID- 4027828 TI - Chronic glossopharyngeal neuralgic pain associated with mucoepidermoid carcinoma. PMID- 4027829 TI - Congenital rubella syndrome in Nova Scotia. PMID- 4027831 TI - Beyond health care: proceedings of a conference on healthy public policy. PMID- 4027830 TI - Trends in the study of medicine in Canada. PMID- 4027832 TI - Towards a healthy world. PMID- 4027833 TI - Person, society and planet: the changing context for health. PMID- 4027834 TI - Beyond Lalonde-creating health. PMID- 4027835 TI - Healthy people. PMID- 4027836 TI - Education for life-long learning. PMID- 4027838 TI - Health and empowerment. PMID- 4027837 TI - Families and health. PMID- 4027840 TI - Public policies for healthy work-places. PMID- 4027839 TI - Developing human potential--an awakening process. PMID- 4027841 TI - Work and health: the changing context and changing roles. PMID- 4027842 TI - Health promoting work. PMID- 4027844 TI - Unemployment and the social contact. PMID- 4027843 TI - Managing technological change in the workplace. PMID- 4027845 TI - A healthy public policy for healthy communities. PMID- 4027846 TI - The environment we create. PMID- 4027847 TI - Community support networks: current issues. PMID- 4027849 TI - Care in the community. PMID- 4027848 TI - Housing and the community. PMID- 4027850 TI - Healthy nations: creating a new ecology of public policy for health. PMID- 4027851 TI - Health, food, water and agriculture. PMID- 4027852 TI - Beyond health care: from public health policy to healthy public policy. PMID- 4027853 TI - Economic policy--as if people mattered: towards health-promoting economic policy. PMID- 4027854 TI - Health implications of new information technologies. PMID- 4027855 TI - Symposium: gender and schizophrenia. PMID- 4027856 TI - The insanity defence. AB - The recent A.P.A. Statement on the Insanity Defence is a document important to all psychiatrists and medicolegal professionals in North America. Its contents are reviewed and contrasted with current Canadian practice on the insanity defence, as well as the proposals of the Mental Disorder Project of the Canadian Department of Justice. The American Psychiatric Association's proposal on the definition of mental disorder is contrasted with the current practice. It is also suggested that the proposal of the Mental Disorder Project to change the disposition of insanity acquittees will lead to difficulties similar to those which provoked the current crisis in the United States. PMID- 4027857 TI - Psychopathology in the offspring of parents with bipolar affective disorders. AB - Thirty-nine children from intact families with a manic-depressive parent were evaluated by a semi-structured clinical interview and a number of rating scales for the presence or absence of psychopathology. This sample represents a larger one than in an earlier study, which showed minimal offspring psychopathology compared with reports of other investigators. The current study also examines the inter-relationships between the presence or absence of offspring psychopathology with both genetic loading and a number of psychosocial variables including measures of parental marital adjustment, severity and chronicity of proband parent illness and early exposure of children to parental illness. Nine of the thirty-nine children, (23%) received a positive DSM-III diagnosis, with depression of the dysthymic type being the most common. There was no significant correlation between genetic loading and offspring psychopathology. However, there were significant associations between children with psychopathology and paternal marital dissatisfaction and the age and chronicity of illness of the proband parent as compared with the children with no psychopathology. PMID- 4027858 TI - Evaluating attitudes of child psychiatry residents to psychotropic medication: implications for training. AB - The attitudes of child psychiatry residents toward the use of psychotropic medication in child psychiatric practice were studied. Eighteen residents underwent a semistructured interview that covered their experience in child psychiatry, beliefs about etiology of child psychopathology, preferences for treatment, attitude toward and experience with drugs in treating childhood disturbances. The residents favored a psychosocial view of the etiology of child disturbance and preferred family therapy to other forms of treatment. Six had never treated a child with medication and most were uncertain about indications for drug use and felt they had less than average or poor skills in this area. Seven residents, who did not attend department psychopharmacology seminars and had little clinical experience with drugs, had a strong antipathy toward their use. Experience with and attitude toward drug use could not be predicted from the residents' appraisal of their own competence in this field, their experience in child psychiatry, their appreciation of the biological contributions to child psychopathology, or their future practice plans. PMID- 4027859 TI - The classification of personality disorder: I. The choice of category concept. AB - Some common clinical statements about patients with personality disorder are examined for their implications in the choice of category concepts for classifying personality. Clinicians seem to assume that personality categories are imprecise and that membership is probabilistic. These assumptions run counter to those of current classifications. The fact that most cases of personality disorder show features of more than condition creates difficulties for categorical systems. Dimensional systems are frequently proposed as a solution to this problem. Such an approach is rejected at the present time since there is no consensus regarding basic dimensions. Polythetic and prototypic categories are examined as alternatives. It is suggested that prototypic categorization provides an approach that is more in accord with clinical judgement. This approach, based upon Wittgenstein's concept of family resemblances, is better able to accommodate the imprecise or fuzzy nature of personality categories, although it does require some modification to the way categories are defined, and to the way diagnostic reliability is assessed. PMID- 4027860 TI - The classification of personality disorder: II. The problem of diagnostic criteria. AB - Although operational definitions have led to improved reliability of psychiatric diagnoses generally, this is not the case for personality disorders. It is suggested that this is due to a failure to develop definitions composed of criteria that can be reliably identified. Instead, extensive use is made of traits and other dispositions as criteria for assessing these conditions despite an extensive literature indicating that trait judgements are unreliable. The reasons for the low reliability of trait judgements are discussed, and the use of behavioral criteria is advocated as one way to increase diagnostic reliability. The results of a preliminary investigation show that the reliabilities of clinicians' judgements of the behaviors associated with Schizoid, Histrionic, and Compulsive Personality Disorders are comparable to the reliabilities of their judgements of the traits associated with these conditions. These results support the feasibility of developing behavioral criteria for assessing personality. PMID- 4027861 TI - ECT in an acutely psychotic pregnant woman with actively aggressive (homicidal) impulses. AB - The specific use of ECT to control homicidal impulses in a pregnant, acutely psychotic schizophrenic patient is described, with no adverse effects to the mother or the baby. Besides the relative safety of the procedure during pregnancy, the need for monitoring foetal effects is stressed. Although literature is abundant on various aspects of ECT (1-3) there has been little written on its use in pregnancy (4-6) for its value in treating severe depressive illness or certain types of schizophrenia; without adverse effect to the mother and the baby, and where there is a risk-benefit advantage to its use. Nineteen hundred and eighty-four marked 50 years in the history of the use of convulsive therapy (Metrazol) since its introduction into the realm of psychiatry by the Hungarian psychiatrist, Ladislas Meduna. Electro-convulsive therapy (ECT) has been the subject of much controversy among the lay public and some professionals alike in recent years, even though it is generally considered to be one of the most effective treatments available in psychiatry. The Canadian Psychiatric Association (7), the American Psychiatric Association (8), and the Royal College of Psychiatrists (U.K.) (9) have made their position clear on the issue. In a recent Canadian survey of the use of ECT, Smith concluded, "Some of the reported rates are below the predicted minimum levels" indicating that "certain patients have been deprived of the most effective treatment available" (10). PMID- 4027862 TI - Desipramine-induced delirium at "subtherapeutic" concentrations: a case report. AB - An elderly patient treated with low dose Desipramine developed a delirium while her plasma level was in the "subtherapeutic" range. Delirium, which may be induced by tricyclic drug therapy in the elderly, can be caused by tricyclics with low anticholinergic potency. Therapeutic ranges for antidepressants that have been derived from general adult population studies may not be appropriate for the elderly. Further studies of specifically elderly patients are now required to establish safer and more appropriate guidelines for drug therapy. PMID- 4027863 TI - Is there an obsessive psychosis? Aetiological and prognostic factors of an atypical form of obsessive-compulsive neurosis. AB - The study explores whether an atypical form of obsessional illness can be delineated and separated from the conventional form of obsessive-compulsive neurosis (OCN). From a group of 45 obsessive patients, 8 were selected on the basis of 3 criteria: presence of a severely debilitating main obsessive symptom; bordering on the delusional; no schizophrenic symptoms. Assessment and outcome measures included the Psychiatric Questionnaire, the Leyton Obsessional Inventory, Fear Survey Schedule, and IPAT Self-Analysis Form. Self-assessment forms allowed patients to make social adjustment and neurotic symptom ratings. In a multimodal approach, patients were assigned to behavioural and pharmacological treatments on the basis of severity. Reassessment took place after 50 sessions of therapy. Results of analysis of variance statistics indicated that the atypical group had a more malignant form of illness, with more varied and severe obsessions. A poorer prognosis for the atypical group was indicated by: greater social maladjustment, poor employment records, illness of longer duration showing no remissions despite more courses of treatment, and poor response to treatment throughout. The atypical group manifested fewer characteristic features of OCN (example: fewer precipitating events). On the other hand, schizophrenia was not imputed, although delusion-like experiences in the atypical group suggest a psychotic form of illness. The term "obsessive psychosis" suggested by Strauss and recently investigated by Weiss et al and Robinson et al is proposed for our atypical group. Results are compared with those of other investigators. It is concluded that the delineation of a subgroup of obsessional illness is desirable for research and therapy since a form of atypical obsessional illness or obsessive psychosis can be differentiated on aetiological, phenomenological and prognostic factors. PMID- 4027864 TI - Patterns of relapse in locally advanced head and neck cancer patients who achieved complete remission after combined modality therapy. AB - Relapse patterns in patients with locally advanced head and neck cancer who achieved complete remission were evaluated. After combined modality therapy with induction chemotherapy followed by surgery and/or radiotherapy, 71 of 103 patients were clinically free of disease. The 5-year recurrence rate was estimated at 51%, with a 39% local and 26% distant failure rate by 5 years. The factors significantly affecting the relapse patterns were: the site of the primary tumor (those with oral cavity lesions were more likely to fail locally, whereas hypopharynx patients had a higher risk of distant metastases); the type of definitive local treatment (those patients who received surgery and radiotherapy were at lower risk of pure local failure); TN Stage (patients with T4N3 or T3N3 tumor were at higher risk of both local and distant failure); and time to response and presence of oropharyngeal lesions (patients who had a longer period from diagnosis to final complete response [CR] and patients with oropharyngeal primaries were at higher risk for simultaneous local and distant failure). Type of chemotherapy, patient age, tumor differentiation, and response to induction chemotherapy did not significantly influence the patterns of relapse. A combined modality approach with induction chemotherapy, surgery, and/or radiotherapy does not seem to reduce the incidence of distant metastases significantly. PMID- 4027865 TI - A therapeutic approach to primary adenocarcinoma of the cervix. AB - Retrospective study of 97 patients with primary adenocarcinoma of the uterine cervix was undertaken to evaluate the efficacy of two treatment methods, radiation alone and radiation plus surgery. Of 31 Stage I patients, 16 were treated with radiation alone and 15 with combined radiation plus surgery. There was no difference in 5-year disease-free survival of Stage I patients treated by either method. Of 44 Stage II patients, 30 were treated with radiation alone with 54% survival rate; while 14 were treated with a combined approach, with 86% survival rate. It is apparent from the results of this study that surgery in conjunction with radiation showed a significant improved survival rate from 54% to 86% in Stage II disease. Factors influencing the prognosis appear to be tumor volume, uterine size, and tumor grade. Furthermore, these data suggest that early primary adenocarcinoma of the cervix (Stage I, lesion smaller than 4 cm) can be treated effectively by radiation alone or radical hysterectomy with comparable results. Tumors larger than 4 cm, Stage II or beyond disease, uterine enlargement, a high-grade tumor or barrel-shaped lesion, would necessitate a combined therapy to improve the cure rate. PMID- 4027866 TI - Results of irradiation in the treatment of locoregional breast cancer recurrence. AB - A retrospective review is presented of 255 patients with chest wall and/or regional nodal recurrent breast cancer treated between January 1956 through December 1981 at the University of Texas M. D. Anderson Hospital; 61 patients had such massive or diffuse disease that only palliative irradiation was given, and 194 patients were treated with curative intent and form the basis of this report. All patients treated with radical irradiation received greater than or equal to 4500 rad, and 65% of the patients received boost therapy through reduced fields. Thirty-two percent of patients were treated only to a single recurrent site, 11% of two sites, and 57% to the chest wall and regional nodes. Failure to control recurrent disease within or on the border of the irradiated field occurred in 27% of patients. Of 62 patients treated to the local recurrence site, 27% had further recurrences in adjacent unirradiated sites. The patients with the greatest success for tumor control (78%) and survival at 5 years (48% disease-free) are those patients with histologically negative nodes at time of mastectomy and a single chest wall recurrence. Possible prognostic factors are discussed: initial clinical stage, age of the patient, axillary histology at the time of mastectomy, disease-free interval between mastectomy and recurrence, number and size of recurrences, and prior chest wall recurrence. PMID- 4027867 TI - Iridium afterloading curietherapy in the treatment of pediatric malignancies. The Institut Gustave Roussy experience. AB - Between 1972 and 1980, 58 children with malignant tumors underwent iridium 192 (192Ir) curietherapy at the Institut Gustave Roussy. Data from only 45 of them were reviewed (bilateral retinoblastoma and salvage procedures were excluded). The pathologic diagnosis was rhabdomyosarcoma in 75% of cases, yolk sac tumor in 13% of cases, malignant mesenchymoma in two cases, clear cell carcinoma in two cases, and undifferentiated sarcoma in one case. The two major sites were pelvis perineum (64.5%) and head and neck (31%). The treatment was essentially based on a combination of chemotherapy, which was adapted to the histologic type of the tumor, and curietherapy. Partial surgery was carried out in certain cases, either before chemotherapy for diagnostic purposes, or after chemotherapy to remove infiltrative residual tumor. External beam radiotherapy was used in a few cases in lymph node irradiation. The radioactive material was 192Ir, using afterloading techniques, either intracavitary or interstitially or both. The tumor dose, calculated by computerized dosimetry, was 60 to 65 Gy delivered over 5 to 7 days in the majority of cases. Two patients were lost to follow-up. Thirty-five patients (78%) are alive with no evidence of disease after a mean follow-up period of 5 years. Eight patients died, one of complications related to chemotherapy and seven of the evolution of their disease. The late-complication rate, studied in 33 patients with a minimum follow-up period of 3 years, is 18% (6/33). Curietherapy seems to be a preferable conservative treatment in children with localized and accessible malignant tumors. PMID- 4027868 TI - Wolfe mammographic parenchymal patterns. A study of the masking hypothesis of Egan and Mosteller. AB - Wolfe defined four different classes of breast parenchymal patterns and claimed that they were associated with different risks for the subsequent development of breast cancer. Egan and Mosteller suggested that these patterns did not constitute a true risk factor, rather the effect was caused by the greater difficulty of detecting breast cancers in the dense (P2, DY) patterns compared with the fatty (N1, P1) patterns. Similarly, Mendell believed that a bias was introduced into Wolfe's work by requiring a negative mammogram before a patient entered the study. This study of 221 prevalent and 706 incident cancers followed for up to 10 years indicates that a masking effect does exist, but that it operates in addition to a difference in risk of breast cancer within the four Wolfe classes. Wolfe's hypothesis is found to be valid. PMID- 4027869 TI - Human interferon alpha in malignant lymphoma and Hodgkin's disease. Results of the American Cancer Society trial. AB - Forty-nine patients with non-Hodgkin's lymphoma or Hodgkin's disease were entered into a multi-institutional phase II trial to evaluate the antitumor activity of human interferon alpha, prepared from buffy coats. Interferon alpha was administered intramuscularly in doses of 1 X 10(6) u, 3 X 10(6) u or 9 X 10(6) u daily for 30 days. Objective partial responses were seen in 3 of 18 patients with nodular lymphoma, all at the 9 X 10(6) u dose. Interferon alpha was not observed to be of therapeutic benefit in the other subtypes of non-Hodgkin's lymphoma or Hodgkin's disease. The major toxicities consisted of fatigue, fever, myalgias and weight loss. Serum interferon levels obtained 3 to 4 hours after injection varied widely, even among patients treated at the same dose level. Despite the relatively low doses of interferon used and the brief period of administration, this study extends the earlier observations of the antitumor effect of interferon in nodular lymphoma. These results are discussed in relation to the cumulative experience in human lymphoma using alpha interferons induced in human leukocytes and those produced in bacteria by recombinant DNA techniques. PMID- 4027870 TI - Aziridinylbenzoquinone in recurrent, progressive glioma of the central nervous system. A Phase II study by the Illinois Cancer Council. AB - Aziridinylbenzoquinone (AZQ) was studied in a Phase II protocol for persons with glioma of the central nervous system (CNS) recurrent or progressive after surgery and radiotherapy. Patients received AZQ, 30 mg/m2 intravenously every 3 weeks if previously untreated or 27.5 mg/m2 if previously exposed to cytotoxic drugs. Partial response was defined as a reduction of at least 50% reduction in the product of the two longest perpendicular diameters of the indicator lesion persisting for a minimum of 28 days. Twenty-eight patients are evaluable for response at this time. Objective response (OR) occurred in four (14.3%): two complete and two partial. Stabilization of disease (SD) was seen in 7 (25.0%). Median survival, in weeks, was greater than 46.0 for responders, 41.7 for SD, and 19.3 for those with progressive disease. The survival experiences are significantly different (P = 0.030 [Breslow]). The OR rate was 21.1% in 19 without prior chemotherapy and 0% in 9 previously treated patients. There were two AZQ-related deaths in patients with prior exposure to nitrosoureas (1 CNS hemorrhage; 1 aspiration pneumonia). One patient had an anaphylactic reaction. Three patients whose tumor initially increased in size subsequently had marked tumor shrinkage. AZQ is an active agent that must be used with added caution in patients who have received nitrosoureas. Initial tumor enlargement may precede response. Although response appears to prolong survival, the correlation between stabilization of disease and survival is not well-defined. PMID- 4027871 TI - Adjuvant chemotherapy for medulloblastoma. AB - The use of adjuvant chemotherapy for cerebellar medulloblastoma is controversial. Twenty-one children and adolescents were treated with adjuvant low-dose cyclophosphamide and vincristine following surgery and radiotherapy. With a mean observation period of 6 years, the disease-free survival is 81%. PMID- 4027872 TI - A comparative study of PALA, PALA plus 5-FU, and 5-FU in advanced breast cancer. AB - Sixty-three patients with Stage IV breast carcinoma refractory to standard combination chemotherapy agents such as 5-fluorouracil (5-FU) were entered into a study to determine the efficacy of a multiple dose schedule of N-(phosphonacetyl) L-aspartic acid (PALA) and whether the addition of PALA improves the therapeutic efficacy of 5-FU. Patients were randomized to receive either PALA, 800 to 1000 mg/m2 per day for 5 days every 2 weeks; or PALA + 5-FU, 400 mg/m2 per day for 5 days, and 300 mg/m2 per day for 5 days every 28 days, respectively. The PALA alone arm of the study was closed after 20 patients had been treated and was replaced by 5-FU, 300 to 400 mg/m2 per day for 5 days every 21 days. Overall response rates were 5% for PALA alone, 28% for PALA + 5-FU, and 14% for 5-FU alone. All patients who responded to PALA + 5-FU or 5-FU alone had received prior therapy in which 5-FU was part of the combination chemotherapy program and were considered refractory to this drug. Toxicity affected the gastrointestinal tract but was tolerable in all three arms of the study. Myelosuppression was negligible for PALA and PALA + 5-FU and moderate for 5-FU. The authors concluded that PALA + 5-FU was superior to PALA alone in the therapy of these heavily pretreated patients. PALA alone had marginal efficacy. In view of its low hematologic toxicity, PALA + 5-FU may be combined with more myelosuppressive drugs. Additional studies are necessary to ascertain whether PALA + 5-FU is therapeutically superior to a full-dose schedule of 5-FU. PMID- 4027873 TI - Correlations between leukocyte count and absolute granulocyte count in patients receiving cancer chemotherapy. AB - The absolute granulocyte count (AGC) has been considered the best index for estimating the risk of infection in patients receiving myelosuppressive therapy. However, many investigators and cooperative oncology groups use the leukocyte count and extrapolate concurrent AGC values from an arbitrary conversion scale. Our review of the literature revealed no analysis of the relationship between the leukocyte count and the AGC in patients receiving cancer chemotherapy. It also failed to provide a method for converting toxicity criteria from one scale to the other. To explore the possible relationship of the leukocyte count to the AGC, we have completed a retrospective analysis of leukocyte count and accompanying AGC in patients receiving cancer chemotherapy. The leukocyte count and the AGC are shown to be linearly related over the entire population, enabling predictable cross-indexing from leukocyte count to AGC by the use of the formula: AGC = -0.7 + 0.8 (leukocyte count). This provides a rational basis for the development of guidelines for drug dosing and toxicity. In the patient group with leukocyte count less than or equal to 4500, however, the magnitude of random variability decreased predictive ability. Numerous patients in this group received differing toxicity scale scores when classified according to the Eastern Cooperative Oncology Group (ECOG) scales for AGC and leukocyte count. In some cases, as much as 46% disagreement occurred. New toxicity scales for AGC and leukocyte count, which were developed based upon the linear relationship above, reduced this disagreement substantially. These scales result in a greater agreement of toxicity ratings, and may provide a more accurate method of classifying toxicity and regulating dosages of chemotherapeutic agents. PMID- 4027874 TI - Doxorubicin-induced congestive heart failure in adults. AB - The prognosis of doxorubicin-induced congestive heart failure (CHF) is reported to be poor. To define the clinical course of doxorubicin-induced CHF, the authors reviewed their experience with 43 patients with this diagnosis. The median age of the total group was 55 years (range, 23-69); the median cumulative dose of doxorubicin was 450 mg/m2 (range, 200 mg/m2-1150 mg/m2). A majority of the patients had a diagnosis of breast cancer. The median survival of the whole group estimated by means of a Kaplan-Meier plot was 112 weeks. Twelve of 43 patients (28%) died of CHF, 7 of them (16%) because of fulminant failure in less than 8 weeks and the remaining 5 because of a more protracted course with recurrent episodes of cardiac decompensation. Twenty-five of the 43 patients (58%) achieved complete control of CHF. In the remaining 6 patients (14%), CHF had improved but was not completely controlled at the time of death, which was secondary to progressive tumor. Treatment consisted of standard therapy with digitalis and diuretics. Survival was significantly shorter in patients who presented with class IV dyspnea and in those who developed CHF less than 4 weeks after administration of the last dose of doxorubicin. The authors conclude that in a majority of patients, doxorubicin-induced CHF is easily treatable and frequently controlled with digitalis and diuretics. PMID- 4027875 TI - Composite cerebral neuroblastoma and astrocytoma. A mixed central neuroepithelial tumor. AB - This report describes an exceptional example of cerebral neuroblastoma in association with neoplastic glial cells, which were frequently arranged in clusters around the supporting blood vessels. The neuroblastic nature of the tumor was confirmed by the presence of numerous dense-core vesicles in the cell processes. The glial nature of the associated cells was confirmed by their positivity for glial fibrillary acid protein by immunoperoxidase staining and by the presence of abundant cytoplasmic filaments of intermediate size on electron microscopy. Of particular interest was the presence of dense-core vesicles in some of the glial cells, and that of a basal lamina underlying the perivascular glial cells. The tumor was interpreted as a composite cerebral neuroblastoma and astrocytoma. No undifferentiated neuroepithelial stem cells could be identified. The cytogenesis of this mixed neuroepithelial neoplasm is uncertain. PMID- 4027876 TI - Blood lymphocyte counts with subset analysis in operable breast cancer. Relation to the extent of tumor disease and prognosis. AB - Blood lymphocyte counts and various lymphocyte subsets, as defined by rosette tests, were examined in breast cancer patients and correlated to the extent of tumor disease and prognosis. One hundred sixty-six patients tested before or shortly after surgery were included. It was observed that the frequency of E rosette-forming lymphocytes correlated to the development of distant metastases (P = 0.007) and survival (P = 0.022). A high frequency of E-rosette-forming cells was associated with a poor prognosis. The well-known prognostic value of clinical tumor stage and axillary lymph node involvement was also confirmed. A possible relation between the tumor disease and other immune variables was indicated by the finding that the frequency of EAC-rosette-forming lymphocytes (mainly B cells) was reduced in patients with relatively large primary tumors. This relation was most pronounced in patients without axillary node involvement (P less than 0.01). In addition, it was observed that the blood lymphocyte counts were significantly higher in patients with three or more tumor-involved axillary nodes than in those with zero to two (P less than 0.005). Our results seem to stand in contrast to the generally held view that low lymphocyte counts and a low proportion of E-rosette-forming cells in the blood are associated with a large tumor burden and a poor prognosis. PMID- 4027877 TI - Cystadenoma with mesenchymal stroma (CMS) in the liver and bile ducts. A clinicopathologic study of 17 cases, 4 with malignant change. AB - This study of 17 cases describes a homogeneous clinicopathologic group of tumors previously subsumed under the general term, hepatobiliary cystadenoma. This unique group of neoplasms that the authors have termed "cystadenoma with mesenchymal stroma" (CMS), occurred exclusively in women and showed two essential tumor components: a cyst lining of columnar to cuboidal, mucin secreting epithelium; and a moderately to densely cellular stroma composed of spindle (rarely oval) cells. The stromal element appeared similar to primitive mesenchyme, both on light and electron microscopic study, showing variable differentiation toward fibroblasts, smooth muscle, adipose tissue and capillaries. Cases of hepatobiliary "cystadenoma" in the literature with histology similar to CMS had similar sex and age incidences, while histologically dissimilar cases, lacking the mesenchymal stroma, had significantly different parameters. Four cases of CMS in this series showed malignant change that was manifested as papillary adenocarcinoma, suggesting the need for complete surgical removal of these premalignant neoplasms. PMID- 4027878 TI - Adenocarcinoma of the colon: an autopsy study with implications for new therapeutic strategies. AB - Clinical, pathologic, and autopsy records of 53 patients who had localized adenocarcinoma of the proximal colon and had undergone potentially curative surgery were analyzed to define ultimate patterns of recurrence and final patterns of dissemination. Ten patients (19%) died with locoregional recurrence alone (operative bed and retroperitoneal nodes). Liver metastases were present in 31 patients, accompanied by other sites of infradiaphragmatic failure in 29 patients (94%). Twenty-three patients (43%) died with cancer confined to the abdomen, retroperitoneum, and liver. The distribution of involved sites points to potential refinements in the surgical staging of this cancer and suggests a rational strategy for planning adjuvant therapy designed to address all the principal early mechanisms of disease dissemination. PMID- 4027879 TI - Histologic correlates and virulence implications of endometrial carcinoma associated with adenomatous hyperplasia. AB - The association of endometrial carcinoma (EC) with endocrinopathies manifested by obesity, nulliparity, and/or increased estrogen levels of exogenous or endogenous estrogens is now well-known. EC is also seen in patients without these findings. Are these different cancers? Seventy-four cases of EC were reviewed and classified into two groups: group I, with associated adenomatous hyperplasia (AH), 31 cases; and group II, without associated AH, 43 cases. Group I included more well-differentiated and less invasive carcinomas; histologically, the pattern was glandular in all cases. In Group II, the EC were less well differentiated, more invasive, and included, besides adenocarcinomas, clear-cell, papillary, and anaplastic carcinomas with giant tumor cells. Squamoid features were found in both groups. The possible existence of two types of EC, a hormonal dependent EC associated with AH (which is believed to result from hyperestrogenism, and to have a better clinical prognosis), and an "independent" EC, not associated with AH, is discussed. PMID- 4027880 TI - Female adnexal tumor of probable Wolffian origin with multiple recurrences over 16 years. AB - The case history of a woman with a "female adnexal tumor of probable Wolffian origin" is described in which the neoplasm recurred three times during a 16-year interval and responded with prolonged remission after repeated surgical excision and radiotherapy. Ultrastructural data are given to support the Wolffian nature of the tumor. Although the tumor was considered in the past to be a benign neoplasm, the current report, as well as six others in which the tumor recurred or metastasized, indicates that the female adnexal tumor of probable Wolffian origin should be classified within the International Classification of Disease Oncology and the Systematized Nomenclature of Medicine nomenclatures as "of low malignant potential." PMID- 4027881 TI - Second malignancies in hairy cell leukemia. AB - Among 172 patients with hairy cell leukemia (HCL) seen at the University of Chicago over a 10-year period, 15 were found to have a second malignancy. Neoplasia of the skin was noted most frequently; there were three cases of basal cell carcinoma, one case of anaplastic squamous cell carcinoma, and one case of malignant melanoma. This was followed in frequency by three cases of carcinoma of the lung. The clinical characteristics of these 15 patients did not differ from those of the general population of patients with HCL. A variety of second hematologic malignant disorders and solid tumors were identified. In one case, the second neoplasm occurred before the diagnosis of HCL; six were diagnosed concurrently; and eight followed the diagnosis of HCL. Since HCL is a well defined clinicopathologic entity, patients with HCL who exhibit unusual features of the disease should be investigated further for the presence of second malignancies. PMID- 4027882 TI - Erythema nodosum heralding recurrent Hodgkin's disease. AB - The association of erythema nodosum with Hodgkin's disease is acknowledged, although not well-documented in the literature. Two patients with long remissions of their Hodgkin's disease manifested persistent erythema nodosum beginning 7 and 6 months, respectively, before relapse was clinically evident. The skin lesions in both patients partially responded to treatment with indomethacin, but did not resolve completely until chemotherapy was instituted. Erythema nodosum probably reflects an important change in the balance of biologic forces between the host and the neoplasm, the nature of which can only be speculated upon at this time. Erythema nodosum should be considered a warning signal of impending relapse in a patient with a history of Hodgkin's disease. PMID- 4027883 TI - Nipple aspirates of breast fluid and the epidemiology of breast disease. AB - Epidemiologic data were obtained, and nipple aspiration attempted, from 289 healthy women, 548 women currently having or with a history of benign breast disease, 153 untreated women with breast cancer, and 106 women previously treated by mastectomy. Breast duct fluid was produced in detectable amounts by 59% of the controls and patients with benign or untreated malignant breast disease; in 35% the volume was in excess of 10 microliters. There were more secretors aged 30 to 50 years (72%), than either those who were younger (52%), or older (44%). Overall, 57% of premenopausal women were secretors, compared with 38% of postmenopausal women. Healthy women who had their menarche before age 13 years were more likely to be secretors. Neither parity, age at first completed pregnancy, nor body weight affected secretor status. There was a trend for the 141 benign breast disease patients aged 40 to 49 years to include more women yielding greater than 10 microliter of fluid (57%) compared with 46 controls (39%). Although breast cancer per se did not appear to influence secretor status, postmastectomy patients were more likely to secrete large fluid volumes, an effect that was particularly pronounced after menopause. Hormonal factors related to age and fibrocystic disease risk and endocrine activity after mastectomy may be the principal determinants influencing the secretion of breast duct fluid. PMID- 4027884 TI - Metachronous bilateral adrenal neuroblastoma. AB - A boy with bilateral adrenal neuroblastoma was presented. The left adrenal neuroblastoma was found when he was at 5 years of age and was curatively excised. The right adrenal neuroblastoma was found when he was at 13 years of age and also was totally excised. The authors consider that the case presented is an extremely rare, metachronous primary bilateral adrenal neuroblastoma, reflecting the multicentric origin of neuroblastoma. PMID- 4027885 TI - High-dose cytosine arabinoside in previously treated patients with poor-prognosis non-Hodgkin's lymphoma. AB - Fourteen previously treated patients with relapsed or refractory poor-prognosis non-Hodgkin's lymphoma were given chemotherapy regimens containing high doses of cytosine arabinoside alone (seven patients) or with an anthracycline or amsacrine (seven patients). Five patients achieved a complete remission and two patients had a partial remission. The durations of remission, however, were short (median, 3 months; range, 2-6 months). Toxicities included conjunctivitis, photophobia, stomatitis, dermatitis, cerebellar dysfunction, diarrhea, nausea, vomiting, liver dysfunction, and severe myelosuppression. Recovery of an absolute granulocyte count greater than 500/microliter and an untransfused platelet count greater than 20,000/microliter required a median of 31 (range, 28-35) and 30 (range, 27-43) days, respectively. Six patients died with recurrent or residual disease before bone marrow recovery. Younger age, good performance status, and a previous complete remission were predictive of a good response. High-dose cytosine arabinoside has major myelotoxicity but significant activity in some patients with poor-prognosis non-Hodgkin's lymphoma. PMID- 4027886 TI - Chemotherapy for inoperable infantile fibrosarcoma. AB - Infantile fibrosarcoma, an uncommon disease of childhood, generally occurs in an extremity and despite high local recurrence rates is usually curable with surgical excision alone. Two patients whose tumors were unresectable because of extensive retroperitoneal involvement are reported. Treatment with doxorubicin, vincristine, and cyclophosphamide resulted in complete clinical responses in both patients. They remain alive and tumor free 2.5 and 4 years from diagnosis. Chemotherapy as a single modality appears to be effective in controlling unresectable infantile fibrosarcoma. PMID- 4027887 TI - TNO-6-induced acute renal failure. A case report. AB - A case of fatal acute renal failure during treatment with 1,1-diaminomethyl cyclohexane sulphato platinum II (TNO-6) is reported. Pathologic investigation showed focal tubular necrosis with interstitial infiltration and edema. Despite the development of proteinuria no changes of the glomeruli were found, either by light or electron microscopic investigation. The pathologic changes caused by TNO 6 are similar to those found in renal failure caused by cisplatin (CDDP). PMID- 4027888 TI - Thymic hyperplasia following successful chemotherapy. A report of two cases and review of the literature. AB - True thymic hyperplasia is rare in adults. The authors have encountered this entity in two patients who were deemed disease-free following combination chemotherapy for malignant disease. It cannot be assumed that the development of a mediastinal mass or its persistence following chemotherapy is due to recurrent or residual disease. The interrelationship between the immunosuppressive effects of neoplasia and chemotherapy with the resultant thymic overgrowth remains to be clarified. PMID- 4027889 TI - Hyperparathyroidism subsequent to neck irradiation. Risk factors. AB - A follow-up examination of 444 persons treated with x-rays for tuberculous cervical adenitis was performed to determine if the risk for hyperparathyroidism (HPT) following radiation exposure can be related to the age at treatment, the dose of x-rays, or the sex of the patient. The overall incidence of HPT was 14%. There was no definite age-dependent difference in susceptibility to the induction of HPT. The doses of radiation among the 63 subjects who developed HPT ranged from 0.6 to 45.7 Gy (60-4570 rad). There was a statistically significant positive correlation between the dose of radiation and the probability of developing HPT. After doses of 14 Gy (1400 rad) or more 29% of the subjects had developed HPT. After neck irradiation women had twice the relative risk of men of developing HPT. This sex ratio was lower than in the series of nonirradiated HPT patients treated at the same institution during the time of the follow-up study. PMID- 4027890 TI - Comparison of peripheral blood lymphocyte C3 receptor capping properties in patients with chronic lymphocytic leukemia and lymphoma. AB - Bacteria-antibody complexes were used to study capping of receptors for the activated third component of complement on peripheral blood lymphocytes. The impairment of C3d receptor capping improves in patients with chronic lymphocytic leukemia responding to therapy, but this does not necessarily correspond to the fall in peripheral lymphocytosis. Following lymphapheresis, increased capping appears to be due to selective removal of noncapping cells, but the mechanisms of improvement remain unexplained following other therapeutic measures. Lymphoma capping at 37 degrees C was normal in untreated patients but impaired after treatment, suggesting that this is related to the therapy itself. A high proportion of lymphocytes had receptors in the capped configuration in the basal state before incubation. In non-Hodgkin's lymphoma this was unrelated to treatment status, but it occurred only in untreated patients with Hodgkin's lymphoma with no further increment in capping after incubation. These receptors may exist in the aggregated state without the addition of exogenous ligand. PMID- 4027891 TI - The relationship of clinical status and therapeutic modality to natural killer cell activity in human breast cancer. AB - The role of clinical status and therapeutic intervention on natural cell-mediated cytotoxicity in breast cancer was ascertained by monitoring natural killer (NK) cell activity in peripheral blood samples. Patients with localized disease on chemotherapy showed significant reductions in NK activity concomitant with reduced lymphocyte numbers, when compared to untreated patients (18.1% versus 32.7%, P less than 0.005). Lymphocyte counts were included in a calculation of the absolute proportion of NK activity that incorporates a correction factor for the leukopenia that occurs as a result of cytotoxic therapy and disease progression. This calculation more accurately reflects the significant reduction of NK activity that occurs in patients with localized and systemic disease on chemotherapy when compared to untreated patients with no current evidence of disease (10.3% and 14.9% versus 30.7%, respectively; P less than 0.001). Different chemotherapeutic regimens were found to selectively affect NK cell function. The levels of both actual and absolute NK activity were significantly reduced in patients receiving 5-fluorouracil and L-phenylalanine mustard; cyclophosphamide, methotrexate, and 5-fluorouracil; and vincristine, Adriamycin (doxorubicin), and 5-fluorouracil, whereas only the levels of absolute NK activity were significantly reduced in patients receiving mitomycin, Megace (megestrol acetate), and Adriamycin when compared to untreated cancer patients. In contrast, tamoxifen-treated patients demonstrated levels of actual and absolute NK activity observed with untreated cancer patients. Patients receiving tamoxifen showed significantly elevated NK activity when compared to patients on all other chemotherapies. These results indicate that monitoring NK cell function may be useful in assessing the immunosuppressive effects of chemotherapeutic intervention. PMID- 4027893 TI - Ductal spread in prostatic carcinoma. AB - The histologic appearances of ductal invasion were studied in 139 cases of prostatic adenocarcinoma diagnosed in the Department of Pathology, Howard University Hospital, during the period January 1980 through October 1983. Intraductal spread was found in almost half (48%) of the prostatic glands examined. Ductal spread was associated with the local extent (P less than 0.001) rather than with the grade of the tumor (P less than 0.01). Three distinct patterns of ductal penetration were recognized. The duct wall was completely destroyed in microinvasion. In foci of ductal permeation the integrity of the basement membrane was generally preserved, and the duct wall was infiltrated mainly by solitary tumor cells. When the tumor spread was by extension in continuity within the duct wall, the neoplastic cells appeared to grow between the pre-existing epithelial layers. It was concluded that prostatic carcinoma cells have the ability to penetrate the wall of benign ducts and progressively replace the normal epithelial elements. In this process the general framework of the affected duct appears to be preserved. PMID- 4027892 TI - Ultrastructural evidence of dimethylformamide-induced differentiation of cultured human colon carcinoma cells. Increased expression of desmosomes. AB - N,N-dimethylformamide (DMF) induces differentiation of human colon carcinoma (DLD 1) cells in culture and reduces their tumorigenicity in nude mice. The current investigation analyzed DLD-1 (clone D) cells for ultrastructural evidence of differentiation. Examination of treated and untreated confluent monolayers by transmission electron microscopy revealed an occasional intracytoplasmic lumen indicative of adenocarcinoma. DMF-treated cells showed no signs of a toxic reaction. Cytoplasmic organelles were essentially unchanged except for an increase in tonofilaments and associated desmosomes. The number of desmosomes per unit length of contiguous cell border increased almost sixfold in treated monolayers. No other type of cell junction was seen. The increased frequency of desmosomes in DMF-treated cultures is significant because of the direct correlation known to exist between the number of desmosomes and degree of differentiation of some human carcinomas. Desmosomes serve as foci of cell adhesion and are reduced in number in some invasive tumors. Whether the supernumerary desmosomes in DMF-treated cells contribute to the reduction in malignant behavior of these cells in vivo remains to be determined. PMID- 4027894 TI - Correlation of human bladder tumor recurrence with changes in clonogenicity of urothelial cells. AB - Over a 2-year period 340 cystoscopies were performed on 174 patients (126 men and 48 women) followed up for previously treated transitional cell tumor of the bladder or new cases suspected of having bladder tumor. Bladder washings taken at cystoscopy in 66% yielded cells for clonogenic assay. Patients with transitional cell tumors had an average clonogenic index (CI) of 14 (+/- 5) colonies per 10(5) viable urothelial cells, whereas previously tumorous patients with tumor-free bladders had an average CI of 6 +/- 1 colonies (P less than 0.001, Student's t test). Patients with hematuria but no bladder tumor had an average CI of 8 (not significant). In serial examinations with consecutive successful clonogenic assay, 11 of 16 patients remaining tumor-free had constant or falling CI whereas 9 of 12 patients with recurrent tumor had rising CI values (Fisher; P less than 0.025). Changes in the clonogenic index of cells taken from bladder washings paralleled the changes in tumor status at cystoscopy and might have predictive value in this disease. PMID- 4027895 TI - Extracapsular spread of carcinoma in cervical lymph nodes. Impact upon survival in patients with carcinoma of the supraglottic larynx. AB - The treatment results and histologic findings in the cervical lymphatics of 96 patients with squamous cell carcinoma of the supraglottic larynx were studied retrospectively. The clinical assessment of the extent of disease in the cervical lymphatics correlated poorly with histologic findings. Forty-one percent of patients judged to have no evidence of cervical metastases were found to have carcinoma in the cervical lymphatics. Twenty percent of patients judged clinically NO were found to have extracapsular spread of tumor. Patients were subdivided according to the histologic findings in the cervical lymphatics. Three year no-evidence-of-disease (NED) follow-up was available on all patients. Patients with no tumor in cervical lymphatics had a 71% 3-year NED. By comparison, patients with cervical metastases confined to the lymph node were 79% NED. Patients with histologic evidence of extracapsular spread of tumor were 45% NED (P less than 0.05). The use of histologic findings in predicting prognosis and treatment planning is discussed. PMID- 4027896 TI - Diagnosis and grading of malignancy in squamous epithelial lesions of the larynx with DNA cytophotometry. AB - For diagnostic purposes 14 histologically benign, 15 dysplastic, and 16 malignant squamous epithelial lesions were subjected to DNA cytophotometry. Results were computed according to an algorithm for DNA diagnosis and grading of malignancy. In cases of unequivocally malignant or benign lesions all DNA diagnoses agreed with the histologic diagnoses. In one case the allegedly faulty DNA diagnosis of cancer was proven to be correct on clinical follow-up. Within the group of histologically mild to moderate dysplasias the algorithm identified four cases as malignant that were proved to be malignant either in the follow-up or at another site of the same lesion. With the aid of the DNA malignancy grade two groups of patients with squamous epithelial carcinomas of the larynx could be discerned with a highly significant difference according to their survival times. PMID- 4027897 TI - Papillary duct hyperplasia of the breast in children and young adults. AB - Papillary duct hyperplasia (papilloma and/or papillomatosis) are relatively common breast lesions in adult women. However, they are rarely seen in women younger than 30 years of age or in children. This report presents the findings in 38 children and young adult women aged 10 to 26 years (average, 17 years). Six (16%) were younger than 14 years of age and 31 (82%) were 20 years or younger. Three types of papillary duct hyperplasia were described as papilloma (9 cases), papillomatosis (9 cases), and sclerosing papillomatosis (20 cases). None of these lesions exhibited the prominent cystic component of juvenile papillomatosis (JP) and most lacked other features of JP such as apocrine metaplasia and stasis. Other than a slightly older average age at diagnosis for sclerosing papillomatosis, no significant clinical differences were found related to the patterns of papillary duct hyperplasia. Thirteen percent reported a positive family history for breast carcinoma. No carcinomas have been detected in the 38 patients (follow-up, 14-307 months) and only one subsequent carcinoma was described after an interval of 22 years among 36 other cases reported in the literature. A family history of breast carcinoma is reported in 28% of JP cases and 5% have associated carcinoma. Further follow-up will be necessary to fully define the natural history of papillary duct hyperplasia in these young patients. There appear to be sufficient morphologic and clinical differences from JP to warrant a separate diagnostic term for this group of lesions. Treatment should be local excision. PMID- 4027898 TI - The value of urinary polyamine assay in stomach cancer. Comparison with serum carcinoembryonic antigen. AB - The authors recently established a new simple enzymatic assay method for total urinary polyamines (Cancer Res 1983; 43:2263-2367). In order to assess the clinical usefulness of measuring total urinary polyamines for the detection of cancer, this method has been applied to the assay of polyamines in the urine of 45 patients with stomach cancer who were classified as to clinical stage. In addition, the value of serum carcinoembryonic antigen (CEA) in the same individual patients was measured for comparison. Percentage of patients with elevated levels of total urinary polyamines increased with International Union Against Cancer (UICC) clinical stage, and was 40.0% (6/15), 50% (3/6), 72.7% (8/11), and 84.6% (11/13) for Stage I, II, III and IV stomach cancer patients, respectively. In 32 patients with stomach cancer of potentially operable Stage I, II, and III, elevated levels of total urinary polyamines were found in 17 patients and elevated levels of serum CEA were found in 5 patients. In 13 patients with inoperable stage IV stomach cancer, elevated levels of total urinary polyamines were found in 11 patients and elevated levels of serum CEA were found in 5 patients. Statistical differences in the detection rate were found between the two markers in these two groups of patients. The combination of these two markers did not increase the detection rate of stomach cancer significantly. The data indicate that the determination of total urinary polyamines by the new assay is clinically useful as a potential marker for the detection of advanced stages of stomach cancer and may be more useful than that of serum CEA. Furthermore, this study demonstrates the relationship between urinary polyamine levels and tumor regression and also the prognostic significance of polyamine determination in stomach cancer patients. In 6 of 13 patients who showed elevated levels of urinary polyamines before surgery, polyamine levels fell to within the normal range after successful surgical removal of tumor. In general, each polyamine level decreased significantly following surgery by paired Student's t test analysis. All of the five Stage IV patients with polyamine levels greater than 4.0 mumol/kg/24 hour died in less than 3 months whereas five of eight Stage IV patients with polyamine levels less than or equal to 4.0 mumol/kg/24 hour survived 10 to 20 months. Statistical differences in survival were observed between Stage IV patients with polyamine levels greater than 4.0 mumol/kg/24 hour and those with polyamine levels less than or equal to 4.0 mumol/kg/24 hour.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 4027899 TI - Flow cytometric analysis of DNA content in human bladder tumors and irrigation fluids. AB - Flow cytometry (FCM) was used to study the DNA distribution of 99 tumor biopsy specimens and 41 bladder irrigation samples from patients with transitional cell carcinoma of the bladder. For tumor biopsy and cystectomy specimens, the frequency of aneuploidy increased with advancing tumor stage and grade. All T0 tumors were diploid. Twenty-seven percent of T1, 71.4% of T2, and 75% of T3 and T4 tumors were aneuploid. All Grade I tumors were diploid. Thirty percent of Grade II and 76.9% of Grade III tumors were aneuploid. The frequency of aneuploidy of tumors in the early stages (Ta, T1) is similar to the incidence of subsequent progression by these tumors described in the literature. For irrigation fluids, the relationship between grade and stage and the frequency of aneuploidy was similar to the relationship seen with tumor specimens. All four patients with only carcinoma in situ had aneuploid cells in their irrigations. The comparison of FCM data of bladder biopsy and bladder irrigation from the same cystoscopic evaluation suggests adequate representation of tumor cells in the irrigation fluids for almost all cases. The authors conclude that DNA ploidy analysis by FCM appears useful in a clinically important group of patients with aneuploid superficial tumors of moderate or high grade. Bladder irrigation analysis appears useful in the follow-up of patients with a history of carcinoma in situ and those with aneuploid tumors. PMID- 4027900 TI - Significance of estrogen and progesterone receptors, disease-free interval, and site of first metastasis on survival of breast cancer patients. AB - Estrogen and progesterone receptors (ER/PR) were measured in primary tumors and metastases of 397 breast cancer patients. Survival following mastectomy was significantly longer in patients with ER and PR positive tumors, as was survival after first recurrence. The prognostic value of ER and PR was compared with such clinical factors as disease-free interval (DFI) and the dominant site of first metastasis by Cox's regression analysis. With all the different therapy modalities long DFI was the best prognostic indicator. However, in the patient group treated with endocrine therapy, ER and PR positivity was the best prognostic indicator, suggesting that longer survival in receptor positive patients was related to the response to endocrine treatment. PMID- 4027901 TI - Race-related differences in breast cancer patients. Results of the 1982 national survey of breast cancer by the American College of Surgeons. AB - Data from the 1982 breast cancer survey of the American College of Surgeons were used to evaluate factors related to clinical, epidemiologic, and survival differences between black and white patients. Breast cancer in blacks was not discovered as early as in whites. Distribution of pathologic types of tumors were similar for both races with the exception of medullary carcinoma, which was more frequent in blacks than in whites. Estrogen receptor-positive tumors were found significantly less frequently in blacks compared with whites. Survival was better for whites compared with blacks within each axillary nodes group 0, 1 to 3, and 4+. Black women with negative or positive estrogen receptors had lower survival rates than white women of the same receptor status. A regression analysis using Cox's proportional hazards model showed race, clinical stage or axillary nodal status, age at diagnosis, and estrogen receptor status as significant predictors of survival. Significant differences between black and white patients were also observed with respect to the report of family history of breast cancer, age at first pregnancy, number of pregnancies, and age at cessation of menses. PMID- 4027902 TI - Prevention of colon polyposis and carcinomas by right hemicolectomy and indomethacin in animal model. AB - Rats were given intrarectal instillations of N-methylnitrosourea. The experimental groups with right hemicolectomy and oral indomethacin had a significantly reduced rate of large bowel tumors. The inhibition rate of tumor development was 88% in incidence and 94% in number. This inhibition was associated with a decrease of fecal bile acid level and a shortened intestinal transit time. It was hypothesized that the change of fecal bile acid composition after surgery and the prostaglandin synthesis inhibition by indomethacin affected the promotion phase of large bowel carcinogenesis. PMID- 4027903 TI - Metastatic neuroblastoma and testicular involvement. AB - Neuroblastoma metastatic to the testes is thought to be an extremely rare event and is therefore not routinely considered in the evaluation of neuroblastoma patients. A review of metastatic sites in a series of neuroblastoma patients, however, revealed 11 cases with testicular involvement. Analysis of these cases suggests that the phenomenon may not be uncommon in a subset of neuroblastoma patients, namely, male patients with infra-diaphragmatic primaries and advanced stage disease. Because the testes constitute a sanctuary site for tumor cells, occult testicular involvement may play a role in the relapse of patients judged to be in complete remission. Accordingly, it is proposed that in the above group of patients special diagnostic attention should be directed at the scrotal contents and, if testicular involvement is detected, orchiectomy or local irradiation should be considered. PMID- 4027904 TI - American Cancer Society Workshop Conference on Pediatric Brain Tumors. Niagara-on the-Lake, Ontario, Canada, June 18-20, 1984. PMID- 4027905 TI - Computed tomography in the diagnosis of intracranial neoplasms in children. AB - The authors discuss their original observations using computed tomography (CT) in the diagnosis of posterior fossa neoplasms in children. The subject of CT diagnosis of childhood supratentorial tumors is also reviewed. However, despite the documented value of CT, the authors believe that magnetic resonance imaging (MRI) will eventually offer certain advantages that will make MRI the primary imaging modality for intracranial neoplasms in children. PMID- 4027906 TI - Radiologic guidelines in assessing children with intracranial tumors. AB - Computed tomography (CT) is currently the primary and generally the definitive imaging modality for the diagnosis, evaluation, and management of intracranial neoplasms in children. The value of CT in the postoperative period is discussed. The role of CT and myelography is stressed in the evaluation of cerebrospinal fluid seeding. CT is also important in demonstrating the iatrogenic disturbances of the central nervous system as a result of radiation and chemotherapy. The authors recommend that CT scans with and without contrast be obtained 2 weeks after surgery and before starting any form of adjuvant treatment. CT slices should be contiguous and 5-mm thick. Subsequent scans should be obtained every 3 to 4 months for the first year and every 6 months thereafter. Where necessary, CT scans after the introduction of intrathecal metrizamide may be necessary to evaluate the lower portion of the posterior fossa and brain stem. PMID- 4027907 TI - Myelography for staging medulloblastoma. AB - Thirty-eight patients with newly diagnosed medulloblastoma were studied with myelography and cerebrospinal fluid (CSF) cytology studies before radiotherapy. Seventeen (45%) patients had evidence of dissemination beyond the posterior fossa. Spinal cord lesions were demonstrated in ten patients (26%). Negative results of CSF cytology studies did not preclude demonstration of cord involvement. Children younger than 5 years were more likely than older patients to have spinal cord involvement at diagnosis. Patients who were truly M-0 did better in terms of absolute survival but not relapse-free survival when compared with patients with dissemination. Myelography and cytology studies are necessary in the evaluation of all newly diagnosed patients with medulloblastoma and may also be indicated for patients with other brain tumors with a known propensity for dissemination. PMID- 4027908 TI - Magnetic resonance imaging in the evaluation of intracranial tumors of childhood. AB - Magnetic resonance imaging (MRI) is a noninvasive imaging technique that demonstrates intracranial anatomy without the use of ionizing irradiation and intravenous contrast agents. Image quality is dependent on various factors, including field strength, scanning sequence, and imaging time. Although there is currently no concensus as to how to visualize intracranial lesions optimally, MRI has already been shown to be sensitive in the detection of brain tumors. It can detect many different types of tumors; however, its specificity is unclear. Intracranial tumor extent is extremely well-demonstrated by MRI. The advantages and disadvantages of MRI compared with computerized tomography are reviewed. PMID- 4027909 TI - Extraneural metastases of central nervous system tumors. AB - In the past, extraneural metastasis of central nervous system tumors was considered to be a rare event. However, more recently, a considerable body of literature has accumulated so that to date some 282 patients with extraneural metastases have been reported. Of these reported cases, 40.4% have occurred in children. Although central nervous system tumors can spread spontaneously beyond the confines of the central nervous system, most instances of extraneural metastasis occur after craniotomy or diversionary cerebrospinal fluid shunting. Extraneural metastases are universally fatal. Although it is not curative, chemotherapeutic treatment of metastases may greatly decrease the patient's discomfort and improve the quality and duration of survival. Every effort should be made to prevent this complication by avoiding diversionary cerebrospinal fluid shunting procedures or by incorporating a filtering device if a shunt becomes necessary. PMID- 4027910 TI - Staging of cerebral hemispheric tumors. AB - There is currently no adequate staging system for cerebral astrocytomas. A scheme for acquiring data that can be used to stage cerebral hemisphere tumors is suggested. This data base, in conjunction with treatment and survival information, may be useful in the management of childhood hemispheric tumors. PMID- 4027911 TI - Neurosurgical staging of midline intra-axial (nuclear) tumors. AB - A staging system is needed for midline intra-axial (nuclear) tumors so that treatment results can be compared, insights about tumor biology can be obtained, and prognosis can be estimated. The TNM staging classification is of limited value because nuclear tumor margins cannot be defined by an operation, there are no nodes to sample, and the tumors rarely metastasize. Nuclear tumors can be staged best now by computed tomography (CT) and pathology findings. Diagnostic staging by CT scans will demonstrate tumor features that may be of prognostic importance: tumor size, density, volume, enhancement, laterality, and presence of cysts and calcifications. In the current series, prognosis was better for tumors with cysts or calcifications, and for tumors less than 5 cm, but correlated poorly with laterality and site. Biopsy and often partial resection can be performed on nuclear tumors with low risks, but operative staging is not helpful because operations are necessarily limited. Most diencephalic tumors are astrocytomas or mixed gliomas, but approximately 15% are malignant astrocytomas or malignant mixed gliomas that need more intensive therapy, and 5% to 10% are neoplasms such as hamartomas that require no additional therapy. Two individual histopathologic characteristics, high cell density and mitoses, indicate a worse prognosis. Pediatric brain tumor study groups need to accumulate additional radiographic and pathologic information to stage nuclear tumors more accurately. PMID- 4027912 TI - Tumor staging for pineal region tumors of childhood. AB - The central midline location of the pineal gland, its intricate contact with cerebrospinal fluid pathways, and the generally large size of tumors in this area before they produce symptoms raise problems in the use of TNM classification. Biopsy was performed on 30 consecutive pineal region tumors seen in children detected over an 8-year period. The pathologic features did not conform to previous autopsy data. Germinomas comprised only 7% of tumors, whereas 23% were malignant germ cell tumors. Neither computerized tomography, magnetic resonance imaging scan, nor markers were shown to be diagnostic of pathologic type. It was concluded that the significant factors affecting outcome are tumor cell type and presence or absence or mitoses. Surgical biopsy is recommended for all pineal region tumors in children. At the current time, the data base is insufficient to devise a staging classification specific for pineal region tumors and the TNM system appears largely inappropriate. Thus, it is reasonable to develop a data base for tumors of this region that then may lead to a specific staging system. PMID- 4027913 TI - Intraventricular tumors of childhood. AB - Supratentorial intraventricular tumors in childhood are relatively uncommon neoplasms. They are generally benign lesions with certain anatomic predilection, producing symptoms by local expansion and obstruction of cerebrospinal fluid flow. Increased intracranial pressure occurs without focal neurologic deficit because of their relatively silent central cerebral location. The benign nature of supratentorial intraventricular tumors preclude a formal staging system. Listing of tumor type and anatomic location is sufficient. PMID- 4027914 TI - Systemic staging of supratentorial extra-axial brain tumors in children. Craniopharyngiomas, atypical teratoma and teratoid tumors of the suprasellar region (germinomas), and intracranial teratomas. AB - A staging system has been proposed for the following tumors: craniopharyngiomas, germinomas, and intracranial teratomas. Various aspects of the specific pathologic and growth characteristics of the tumor determines such categorization and subclassification of the tumors. A brief analysis of the clinical aspects in reference to classification is presented. The suggested systems will need to be tested in clinical studies to determine their validity. PMID- 4027915 TI - A staging system for brain stem gliomas. AB - Intrinsic brain stem neoplasms are almost invariably malignant, and irrespective of radiation treatment and chemotherapy, are associated with a very abbreviated survival. It is possible that occasional long-term survival is the result of a radiation-sensitive low-grade astrocytoma. It is suggested that a primary staging system may separate poor-risk and good-risk patient populations and that this classification may be important in assessing future therapeutic options. PMID- 4027916 TI - A classification system for primitive neuroectodermal tumors (medulloblastoma) of the posterior fossa. AB - Tumors of the posterior fossa are described. Although the preoperative staging system of Chang and associates has proven prognostic relevance, a proposed new system may have even greater impact on prognosis because it considers the tumor burden postoperatively. This system (MAPS: metastasis, age, pathology, and surgery) incorporates age and pathologic characteristics into the staging system. The value of this proposed staging system, in particular, the impact of pathology, must be assessed in controlled trials. PMID- 4027917 TI - Surgical staging of cerebellar astrocytomas in childhood. AB - Benign cerebellar astrocytomas of childhood, when removed grossly in toto, have high cure rates and thus can be staged by their surgical resectability. Currently, total tumor resection is limited by attachment to or invasion of the tumor into the brain stem or by evidence of recurrence or metastases. Tumors of the cyst-nodule form are more often amenable to total gross removal because of their discrete margins and lateral placement, which is clear of brain stem structures. However, solid astrocytomas of the cerebellum, with or without visible cysts, may also be surgically cured if there is sufficient clearance from the brain stem. Patients with malignant astrocytomas of the cerebellum or metastases have much poorer prognoses. Preoperative and postoperative staging systems have been suggested based on these assumptions. PMID- 4027918 TI - Ependymomas. Factors in clinical and diagnostic staging. AB - In ependymoma, there is evidence that indicates that age, sex, histologic patterns, functional status, location, duration of symptoms, size, and accessibility to surgical removal influence survival. The role of neuron-specific enolase and other biologic markers must await the accumulation of further information. Further advances in diagnostic imaging, immunodiagnostics, and intraoperative staging should lead to a better understanding of the disease and pinpoint prognostic factors more precisely. A profile that contains important information is suggested; this should eventually lead to the development of a staging system. PMID- 4027920 TI - The design and conduct of clinical trials in childhood brain tumors. AB - The orderly conduct of clinical research trials in pediatric oncology has laid the foundation for modern curative therapy in several childhood malignancies. Such types of large clinical trials are relatively new to pediatric neuro oncology. New treatments such as single and combination chemotherapy agents are studied in a Phase II trial in children with specific recurrent primary brain tumors. Computerized tomography (CT) and magnetic resonance imaging (MRI) scans and myelography allow the accurate determination of objective responses. The relative lack of promising Phase II trials has hampered the design of new Phase III studies for a variety of primary childhood brain tumors. The results of several Phase II trials may be incorporated into a prospective randomized Phase III study in which the endpoint is disease-free survival rather than response rate. Because of the rarity of specific types of primary childhood brain tumors, randomized Phase III trials are conducted more easily by cooperative cancer study groups. This article suggests some guidelines for the conduct of these Phase II and III trials in children with primary brain tumors so that accurate data may be accrued in an efficient manner. PMID- 4027919 TI - The value of surveillance testing in childhood brain tumors. AB - Follow-up procedures in children with brain tumors are designed to confirm tumor response to initial therapy, identify recurrence or progression at the time of potential secondary treatment, and establish the patterns of failure. Serial use of neurologic examinations and computerized tomography scans are outlined for all tumor types. Tumors capable of subarachnoid metastasis (medulloblastoma, ependymomas, pineal/suprasellar germ cell tumors, and pineoblastoma) require periodic assessment of the neuraxis by cerebrospinal fluid (CSF) cytology and myelography to establish the frequency of subclinical meningeal seeding in study settings. Serial analysis of specific biochemical markers for medulloblastoma (CSF polyamines) and germ cell tumors (serum and CSF alpha-fetoprotein and beta human chorionic gonadotropin) are suggested. Serial evoked potentials in brain stem gliomas are recommended. PMID- 4027921 TI - The influence and reliability of neurologic assessment and Karnofsky performance score on prognosis. AB - The neurologic examination is important in the early diagnosis of brain tumors in children. Only in brain stem gliomas may the neurologic examination be better than computed tomographic scans in determining the progression. However, in general, the traditional neurologic examination has little or no value for prognosis. Reversible, associated features of brain tumors such as seizures or increased intracranial pressure may alter the patient's ability to function neurologically, but may not influence the prognosis regarding the tumor status. The Karnofsky functional status, to a large extent, reflects an adult's ability to work and has prognostic value but is largely inapplicable to children. Thus, a quality-of-life scale for children is needed. PMID- 4027922 TI - Toward the development of a play performance scale for children (PPSC). AB - Performance scales (i.e., Karnofsky), as they measure quality of life, have been used effectively as an integral part of repeated assessment of adult cancer patients for the last several years. An equally concise measure of performance has not been developed for children. The task of developing a scale to assess performance in infants, toddlers, school-age children, and adolescents is formidable, as the activity measured should be of equal merit at each age level. Although all childhood cancer patients could benefit from a simple-to-administer, rapid assessment, children with brain tumors have the greatest need for a repeated measure of performance. The goal, then, is to develop a simplified set of criteria that can be used for assessment of children with brain tumors during hospitalization, at the time of clinic visits, and/or at the time of diagnostic procedures when the patient is in a reasonable state of health. The assessment should be able to performed by nonprofessional persons. PMID- 4027923 TI - The long-term effects of cranial irradiation on the central nervous system. AB - Cranial irradiation and chemotherapy may have significant long-term deleterious effects on children with brain tumors. Intellectual deterioration, endocrinopathies, leukoencephalopathy, extraneural metastases, and oncogenesis may all complicate the treatment of central nervous system neoplasia. These long term effects of therapy have important implications, as some are amenable to treatment and others may be prevented by the careful monitoring of drug and radiation administration. Until recently, the survivals of children with brain tumors were limited, so that concerns over long-term effects of therapy were unnecessary. As children with certain types of brain tumors now have a better prognosis, these long-term and possibly remediable effects have important implications. This article emphasizes radiation effects on intellect, endocrine function, and oncogenesis. Recommendations for baseline and longitudinal evaluations of children with brain tumors are suggested. PMID- 4027924 TI - Classifications of childhood brain tumors. AB - Diagnostic classifications of brain tumors do not necessarily reflect natural orders in biology. They are hypothetic statements about relationships among histologic features within tumors that have been fabricated for the purposes of understanding, communicating, and predicting brain tumor biology. Historically, they have been constructed in response to specific needs and have changed to meet new needs. The classifications in use today are built on arbitrary a priori dicta and assumptions that may not stand scientific scrutiny and may obscure efforts of physicians at prognosis. Classifications ignore the influence of site and age upon prognosis. For future use, the differing goals of prognosis and genesis may require different classifications. PMID- 4027925 TI - Statistics of conducting clinical trials for children with brain tumors. AB - Even though intracranial tumors are the second most common neoplasm in childhood, controlled trials for children with brain tumors are unusually difficult to conduct. The major hindrance to these studies appears to be a lack of numbers in each of the histologic subtypes and a lack of an effective collaborative effort among neurosurgeons, neurologists, radiotherapists, and pediatric oncologists, all of whom have some degree of responsibility for the primary care of these children. Improved communication between the Children's Cancer Study Group and the Pediatric Oncology Group, as well as the disciplines mentioned above, could result in significant advances in the understanding and treatment of children with brain tumors. PMID- 4027926 TI - The argument for a combined cancer consortium research data base. AB - Epidemiologic data that were obtained through the SEER registry (Surveillance Epidemiology End Results Program) are presented. Survival statistics for five major brain tumor types in childhood are presented for the years 1968 through 1979. Further survival statistics are compared in patients treated in community hospitals versus university hospitals. The lack of uniform reporting, absence of pathologic conformation, and limited number of patients seen throughout the country are emphasized. There is a need for the establishment of a data base composed of the member institutions of the childhood cancer consortiums. This data base would address questions of patterns of failure, benefits of surgical and clinical staging, and the value of a new putative pathologic grading system. Additionally, the opportunity to collect these patients should permit identification of long-term treatment effects. Identification of early morbidity may lead to modification of treatment programs. A data base containing treatment and diagnostic parameters would allow significant cross-correlations and would lead to the design of future studies that are based upon accurate data. PMID- 4027927 TI - Hodgkin's disease stages IA and IIA. A long-term follow-up study on the gains achieved by modern therapy. AB - One hundred forty-nine supradiaphragmatic Stage IA and IIA Hodgkin's disease (HD) patients treated according to one of two different policies, were analyzed to quantitate the therapeutic gains achieved in recent years. Forty-nine patients were managed according to the pre-1969 policy consisting of mantle radiotherapy (XRT) only without laparotomy staging and without subdiaphragmatic treatment. These cases constitute the old series (OS). Ninety-eight patients after 1969 received staging laparotomy-splenectomy and were treated with total or subtotal nodal irradiation, and in a small number also multiagent chemotherapy (MAC). These patients constitute the new series (NS). All prelaparotomy IA and IIA cases are included in the NS even if they became Stage III at laparotomy. Salvage therapy for relapsing disease differed between the OS and NS. The majority of OS relapsing patients received salvage XRT, while the majority of relapsing NS patients received MAC. The NS and OS patient groups are comparable by pretreatment parameters. There is a large and statistically significant improvement in disease-free survival (DFS) and survival (S) in the NS over the OS. At 13 years the NS group had a DFS of 65% compared to 38% in the OS, and S in the NS was 82% compared to 37% in the OS. The improvement in DFS is almost totally due to the addition of prophylactic periaortic XRT in the NS patients. A striking reversal of relapse patterns for the OS and NS was observed. Periaortic nodal relapse occurred in 37% of the OS patients and accounted for 64% of all relapses, while in the NS this failure pattern occurred in only 2% of all cases. Supradiaphragmatic relapse accounted for 74% of all relapses in the NS. Improved salvage of relapsed patients in the NS further added to the overall gain in survival. Whereas no relapsed patient in the OS achieved long-term survival (14% at 10 years, 0 at 25 years), one-half of NS relapses were salvaged by MAC (54% survival at 10 years from relapse). These data clearly document the striking therapeutic gains in Stage IA and IIA supradiaphragmatic HD resulting from the use of prophylactic periaortic XRT and MAC salvage for relapsing patients. PMID- 4027928 TI - The inhibitory effect of caffeine on hormone-induced rat breast cancer. AB - Studies have associated coffee and/or caffeine with human fibrocystic breast disease. Two animal studies have implicated caffeine as a promoter in rat mammary cancer. The current investigation examines the effect of two caffeine doses in ACI rats with and without diethylstilbestrol (DES). Without DES, cancer did not develop in any of the rats receiving either of the two caffeine dosages. With DES, increasing caffeine dosage lengthened the time to first cancer, decreased the number of rats that developed cancers, and decreased the number of cancers overall. The presence or amount of caffeine did not cause detectable histologic differences in the breast cancers. The presence or amount of caffeine did not influence animal weight or mortality, although the rats without DES weighed more and survived better into old age. The presence or amount of caffeine did not influence pituitary weights and prolactin levels, although values of the DES groups were three times higher than the values for the group without DES (P less than 0.05). In conclusion, chronic caffeine ingestion inhibits rat breast cancer, neither by interfering with the high prolactin levels--a necessary step in murine tumor development--nor by causing hypocaloric intake. PMID- 4027929 TI - Cell kinetics as a prognostic marker in node-negative breast cancer. AB - The relevance of cell kinetics of the primary tumor as a marker of biologic aggressivity was verified on a series of 258 patients with operable breast cancer without nodal and distant metastases, who underwent radical mastectomy without any other treatment until relapse. The cell proliferative rate, evaluated in vitro on fresh tumor material and expressed as 3H-thymidine labeling index, was found to be an important discriminant of metastatic potential. Patients with slowly proliferating tumors showed a higher probability of 6-year relapse-free survival in comparison to those with fast-proliferating tumors (80.5% versus 59.6%, P = 0.00004). This finding was true for premenopausal and paramenopausal (P = 0.00005) as well as for postmenopausal patients (P = 0.01). The kinetic variable was also a discriminant of 6-year survival for the overall series (P = 0.003) and for premenopausal and paramenopausal patients (P = 0.003) regardless of the type of treatment after relapse. These findings show the relevance of the kinetic variable as an important prognostic marker in breast cancer. PMID- 4027930 TI - Distribution and reproducibility of aryl hydrocarbon hydroxylase inducibility in a prospective population study of middle-aged male smokers and nonsmokers. AB - Aryl hydrocarbon hydroxylase (AHH) inducibility was determined in a lymphoblast test system in 2,000 consecutive middle-aged male smokers, 304 ex-smokers, and 218 never-smokers in the same birth-year cohorts. Intraindividual, intraobserver, and interobserver, as well as temporal, reproducibility was checked in a special double-blind quadruplet sample series from 20 other consecutive middle-aged men. The results showed a three-modal phenotype distribution of AHH inducibility with high (fold induction greater than or equal to 3.6), intermediate (2.6-3.6) and low (less than or equal to 2.5) levels ranging between 7.6% to 10.5%, 38.5% to 43.0%, and 46.5% to 53.9%, respectively, in all the smoking categories. The reproducibility of the measurements was excellent, with one-way variance in the order of 0.007 to 0.033, and the applied assay method can therefore be used in large-scale prospective population investigations. Such are required in order to establish a cause-effect association between high AHH inducibility and smoking related malignancies of the respiratory tract and oral cavity, as has been suggested from earlier retrospective studies in more limited clinical materials of cancers and precanceroses of these varieties. PMID- 4027931 TI - The diagnostic value of flow cytometric DNA measurements in follicular tumors of the thyroid gland. AB - Flow cytometric analysis of DNA content was performed on single or multiple samples from 34 thyroidectomy specimens. There were 29 thyroids with diploid DNA content, comprising 15 nonneoplastic lesions, 5 follicular adenomas, 1 medullary carcinoma, and 8 papillary carcinomas. Aneuploid DNA pattern was observed in five cases, including one metastatic mammary carcinoma. The initial histologic diagnoses in the remaining four aneuploid thyroid lesions were follicular carcinoma in one and follicular adenoma in three. The abnormal DNA pattern in the three follicular "adenomas" prompted a review of their aspiration cytologic and histologic features. The fine-needle aspiration biopsy was performed in two of the three cases and showed evidence of a follicular neoplasm with significant nuclear atypia in both. Histologic review of the three lesions led to a modified diagnosis of noninvasive low grade follicular carcinoma in all three. Flow cytometric analysis of DNA content may prove to be a highly useful adjunct in the evaluation of follicular thyroid tumors. Long-term clinical follow-up is warranted to document the clinical significance of these observations. PMID- 4027932 TI - Natural history of pulmonary scar cancers. Clinical and pathologic implications. AB - Twenty-two cases of resected pulmonary scar cancers in which 10 year or greater follow-up could be obtained were evaluated to determine morphologic and clinical criteria which would predict long-term survival and elucidate the cause and effect relationship of the scar to the cancer. Maturity of the scar was found to be an important criterion in predicting long-term survival. Of patients with tumors less than or equal to 3 cm, only one of six with an early scar died with cancer, whereas four of eight patients with advanced scars died with cancer. All tumors greater than 3 cm had advanced scars and five of eight patients in this category died with cancer. These findings support the concept that the scar develops secondary to the cancer and that the maturity of the scar can be used as a prognostic criterion in resected tumors. PMID- 4027933 TI - Ultrastructural diagnosis of epithelial malignant mesothelioma. AB - Examination of microvilli (MV) by electron microscopy (EM) may help distinguish epithelial malignant mesotheliomas (EMM) from metastatic adenocarcinomas (AC). The goal of this study was to assess the diagnostic utility of microvillous length to width (l/w) measurements of EMM and AC, and to determine if ultrathin sections can be used to accurately assess lengths of villi not completely contained within a single section. Therefore, in addition to the usual ultrathin (600-800 A) sections used for standard transmission EM, thicker (up to 1 mu) sections were also prepared for study by scanning transmission EM. Seven cases of EMM and 3 of AC were analyzed. In each case, length and width were measured for all MV with identifiable bases (18-60 MV/case), using an electronic planimeter, and the mean l/w ratio calculated. The dimensionless l/w ratio is independent of magnification and does not require calibration, facilitating intercase comparison. In the 3 AC, the mean l/w was 5.39, versus 11.44 in the 7 EMM cases. Four EMM were analyzed using both standard ultrathin and thicker sections, disclosing a thin section l/w of 13.34 and a thick section of 12.26, supporting the confidence of measurements made from standard ultrathin sections. Examination of data also showed that equally good separation of EMM from AC could be obtained using the mean ratio of only the 10 longest MV (16.11 versus 8.93). By these techniques, EMM often may be distinguishable from AC, with a l/w ratio twice as large in EMM and a mean l/w greater than 11 supportive of a diagnosis of EMM. PMID- 4027934 TI - Reliability of urinary cytodiagnosis in urothelial neoplasms. AB - A retrospective study was done to explore the reliability of urinary cytologic examination of 117 cases of transitional cell carcinoma seen at this institution for the period 1980 to 1984. A specificity of 99%, sensitivity of 85%, false positive rate of 11%, and false-negative rate of 10% were obtained. A single blind review of cytologic and histologic material from 66 of the cases was also performed for evaluation of the cytologic criteria employed for the grading of tumors. Cytohistologic correlation of grade I lesions was poor, whereas correlation of grades II and III was reasonably good. Carcinoma in situ was cytologically recognized in all instances but was difficult to distinguish from grade III carcinoma. PMID- 4027935 TI - Meningeal involvement in patients with acute nonlymphocytic leukemia. Incidence, management, and predictive factors. AB - Between 1977 and 1983, symptomatic meningeal leukemia was diagnosed in 9 of 93 adult patients with acute nonlymphocytic leukemia (10%). All cases occurred after complete remission had been achieved (46 patients), either as the only site of relapse (3 patients), or together with a first bone marrow relapse (3 patients), or after a bone marrow relapse (3 patients). Extramedullary involvement at initial diagnosis was the only independent predictive factor (P = 0.005), the number of patients with initial hyperleukocytosis being too small (three) for evaluation. Remission of the meningeal leukemia was obtained after treatment in four of eight patients. The presence of meningeal leukemia and the response to therapy had no influence on survival. However, the morbidity and therapy related toxicity of meningeal leukemia were impressive. Some recommendations for prophylactic treatment are suggested. PMID- 4027936 TI - Non-Hodgkin's lymphoma associated with pregnancy. A report of six cases, with a review of the literature. AB - Six patients with non-Hodgkin's lymphoma diagnosed during late pregnancy or shortly thereafter are reported. Three patients had high-grade lymphoma and three, intermediate-grade histologic features. Five of the six patients were in Stage 4 and one was Stage 1. Only three had the diagnosis of non-Hodgkin's lymphoma during pregnancy, and in these three cases the disease appeared to progress rapidly after delivery. The other three women probably had lymphoma during pregnancy; lymphoma was widespread at the time of their diagnosis, but the diagnosis was only established on biopsy specimens after delivery in all three instances. Five patients had full-term natural deliveries with normal infants. A single patient with Burkitt's lymphoma had a premature delivery with a cesarean section in the 29th week because of abruptio placentae probably due to lymphoma of the uterine wall. In this case both mother and child died within 48 hours of delivery. The other five patients were treated soon after delivery. Published literature dealing with this topic is scanty and inconclusive; accordingly this report attempts to discuss management of lymphoma in pregnancy, based on the authors' limited experience with these six patients. PMID- 4027937 TI - Familial history of esophageal cancer. AB - Several studies from different regions of the world reflect a positive family history of esophageal cancer among patients with the same disease. The all age standardized rates for the Turkoman of northern Gonbad district in the Caspian Littoral of Iran is as high as 160-180, and truncated rates reach 300-400 per 100,000, the highest incidence rates in the world. A total of 602 esophageal cancer patients (427 Turkoman and 175 non-Turkoman) from this high-risk region were interviewed for a family history of cancer, particularly cancer of the esophagus. Family members were identified as being related by blood or marriage, and the occurrence of esophageal cancer was compared between these two groups. The expected number of cases among blood affines to relatives by marriage has been determined by a formula which takes into consideration several social and ethnic factors; specifically, average family size, the proportion of first cousin marriages and the likelihood of aunts and uncles by marriage also being related by blood. One hundred ninety-nine (47%) of the Turkoman patients in the high-risk area reported a positive family history of esophageal cancer, ranging from 1 to 7 cases in a given family, and involving a total of 299 individuals suffering from the disease of which 244 (82%) were related by blood and only 55 (18%) by marriage. The overall ratio of blood to marriage relatives was 4.4. Forty-six Turkoman patients also indicated that a total of 62 relatives suffered from another cancer, of which 54 (87%) were related by marriage as opposed to only 8 (13%) who were blood affines. Among non-Turkoman (low-risk population) esophageal cancer patients, only 4 (2%) had a total of 5 relatives with the same disease, of whom 2 were by blood and the remaining 3 by marriage. The ratio of blood relatives to relatives by marriage for this group is 0.6, whereas the corresponding figure among the Turkoman population is 4.4. It is evident that there is a familial history of esophageal cancer among this high-risk, ethnic population in the Caspian Littoral. PMID- 4027938 TI - Gastric carcinoma in the West Indies: a Trinidad study. AB - Gastric carcinoma, the commonest cause of death from malignant disease in Trinidad, has decreased steadily over the period 1968-1977. Of the 1052 deaths during this time, females accounted for a relatively high percentage (45%) of cases. There is a predominance of antral tumors, and most cases present with very advanced disease (88% with Stage III & IV). This results in a low resectability rate (32%). Its racial predilection for blacks of the lower income group suggests that both genetic and environmental factors may be important. The possible role of dietary factors is discussed. PMID- 4027939 TI - Diagnostic delay in symptomatic colorectal cancer. AB - Previous research on colorectal cancer patients has suggested that considerable delay can occur once the patient has sought medical care. However, little information has been available on the possible components of this delay. In this study, detailed information on diagnostic delays was collected from 294 symptomatic patients. Of these patients, 46% reported experiencing at least one delay. Three types of diagnostic delay were identified and were associated with different lengths of delay. Of all the delays, 31% were due to difficulties in scheduling initial or subsequent office visits or laboratory tests; these were associated with an average delay of 3 weeks. Physician-related delays (e.g., misdiagnosis or observation of symptoms without specific action) comprised 46% of all diagnostic delays and resulted in an average delay of 18 weeks. The remainder of the delays were patient-related and resulted in an average delay of 12 weeks. There was no association between any of these three delay types, suggesting that attempts to reduce diagnostic delay should encompass all three types in order to be maximally effective. PMID- 4027940 TI - Multiple myeloma and family history of cancer. A case-control study. AB - A hospital-based case-control study was done to examine the hypothesis that persons with a family history of multiple myeloma (MM) or other cancers are at increased risk of multiple myeloma. Study members were 439 cases of multiple myeloma and 1317 matched controls seen at the Duke University Medical Center. Only 3 cases and 4 controls reported multiple myeloma in their families. The relative risk (RR) was 2.3, but the 95% confidence interval (CI) was 0.5-10.1, allowing no firm conclusion about the risk associated with familial MM. A family history of cancer of any type resulted in a relative risk of MM of 1.4 (CI: 1.1 1.8). This association was strongest (RR = 2.5, CI: 1.1-5.3) among young study members (age less than or equal to 49). A family history of hematologic malignancy (ICD 200-208) resulted in a RR of 2.4 (95% CI: 1.4-4.0). The data also suggested that a family history of lung cancer, breast cancer, and genitourinary cancer may be associated with increased risk of myeloma in older persons. PMID- 4027941 TI - Paraplegia in children with malignant teratoma. AB - Two young children presenting with paraplegia secondary to epidural tumors were found to have unresectable malignant teratomas. Following partial resection and aggressive chemotherapy, both patients have done extremely well with disappearance of all disease and dramatic improvement in neurologic function. It is suggested that children with spinal cord compression might have a much better prognosis for recovery of neurologic function than adults. A treatment approach utilizing chemotherapy as the primary mode of therapy is discussed. PMID- 4027942 TI - Surgical treatment of punctal-canalicular fibrosis from 5-fluorouracil therapy. AB - 5-Fluorouracil (5-FU) has been reported to cause punctal-canalicular fibrosis with resultant severe epiphora. It is reported that the epiphora will often resolve when treatment ceases or is decreased. However, this report describes a case of punctal-canalicular fibrosis so severe that bilateral conjunctivodacryocystorhinostomies were necessary. This has not been previously reported to the best of the authors' knowledge. It is recommended that ophthalmic consultation be obtained for patients in whom long-term 5-FU therapy is anticipated or who develop tearing while on therapy. PMID- 4027943 TI - Thymidylate synthetase of human lymphocytes augmented in vitro by methotrexate. AB - The addition of methotrexate to the assay system of thymidylate synthetase caused a reduction in the activity of the enzyme but addition of methotrexate to the culture of phytohemagglutinin stimulated normal human lymphocytes caused an increase in the activity of the enzyme which was abolished by the addition of actinomycin D or cycloheximide. These studies suggest that the antimetabolite augmented the enzyme activity by modulating the gene for the enzyme. This modulation of the gene could have been achieved by the thymineless state brought about by methotrexate or the antimetabolite could have affected gene reodont or brought about amplification of the gene. The results of the nucleoside incorporation were consistent with a thymidylate synthetase block; however, other explanations are offered. PMID- 4027944 TI - Relative roles of K region and bay region towards determining the carcinogenic potencies of polycyclic aromatic hydrocarbons. AB - Using the quantum mechanical MINDO/3 method a bond reactivity index based on superdelocalization of electrons in a compound has been formulated in order to estimate the relative carcinogenic properties of polycyclic aromatic hydrocarbons. The values of the index calculated for the K region as well as the bay region suggest that a knowledge of the reactivities of both regions is necessary for a reasonable estimation of the relative carcinogenic potencies of PAHs. However, no direct relationship between the two reactivity indices was observed in the calculations. It was found that the results for the bay-region reactivity index correlated well with the relative carcinogenic potencies of the molecules. PMID- 4027945 TI - Agarose gel electrophoretic analysis of damage to supercoiled DNA by adriamycin in the presence of beta-NADH dehydrogenase. AB - In a cell-free system, the anticancer anthracycline antibiotic adriamycin was able to convert purified covalently closed circular, superhelical, form I bacteriophage PM2 DNA to relaxed circular form II DNA in the presence of either sodium borohydride (NaBH4), NADPH cytochrome P-450 reductase or beta-NADH dehydrogenase isolated from myocardial cells. There was no detectable increase in the amount of form III linear duplex DNA formed during the reaction even at high drug concentrations. Less drug was required for the conversion of form I to form II DNA in the presence of the enzymic reducing agents than in the presence of NaBH4. Form II DNA, prepared by irradiation using a Cs-137 source, was not degraded to form III linear duplex DNA. However, form I0 DNA, covalently closed circular DNA without superhelical turns, freshly prepared using topoisomerase I, was converted to form II DNA similar to the conversion of superhelical form I to form II DNA. Again, no increase in the amount of form III linear duplex DNA could be detected. PMID- 4027947 TI - The efficacy of direct, 24-hour culture, and mitotic synchronization methods for cytogenetic analysis of bone marrow in neoplastic hematologic disorders. AB - Bone marrow aspirates from 90 patients suspected of having a hematologic disorder were processed by using different cytogenetic methods to determine if any procedure was more likely to reveal a chromosomally abnormal clone or produce better-quality metaphases. All specimens were processed by a direct technique and 24-hr culture without mitogens; 50 specimens were also processed by an amethopterin mitotic synchronization method. In each case, the microscope slides were coded by the processing technologist and analyzed by two other experienced cytogenetic technologists. The results were not known to any of the investigators until all 90 specimens were analyzed. With the exception of one specimen, in which a chromosomally abnormal clone was identified only in the direct preparation, no apparent differences were found in the karyotypes among the three methods. Also, the differences in the quality or number of metaphases found among the three methods were not statistically significant; however, 24-hr unstimulated cultures produced more metaphases than the mitotic synchronization procedure. The greatest source of discordance was caused by one test yielding either no metaphases or an uncertain result when the other tests produced a successful study. We suggest that in routine practice at least two different methods should be used, and it may be best if at least one of these methods is a direct technique. PMID- 4027946 TI - Interrelationships and metabolic effects of fatty acids in the perfused rat liver at hyperthermic temperatures. AB - Livers of fasted rats were perfused for 70 min at 37 degrees-43 degrees C in the presence or absence of acetate, octanoate or palmitate. Hepatic biosynthetic capacity was assessed by measuring rates of gluconeogenesis, ureogenesis, ketogenesis and O2 consumption. In the presence of each fatty acid, gluconeogenesis, ureogenesis and oxygen consumption were maintained at 37 degrees and 42 degrees C. At 43 degrees, the rate of glucose formation decreased markedly and rates of ureogenesis and oxygen consumption were distinctly lower. As the temperature was increased from 37 degrees to 43 degrees C without fatty acids, i.e. albumin only, there was a progressive decrease in the rate of gluconeogenesis while the ratio of net C3 utilized to glucose formed, increased successively. The values of this ratio in the presence of palmitate or octanoate at 43 degrees were smaller than those for albumin or acetate, but higher than the figure of 2 for complete conversion of C3 units to glucose. Although fatty acid was added in equimolar amounts of C2 units, total ketone formation was influenced significantly by chain length. Hepatic ketogenesis was similar at 37 degrees with albumin, palmitate, or acetate, but was stimulated significantly by octanoate at 37 degrees and 42 degrees C. At 42 degrees, ketone formation increased in the presence of palmitate. At 43 degrees C, ketogenesis with palmitate or octanoate decreased, while that with acetate or albumin was maintained at the same lower rates. The ratio of 3-hydroxybutyrate to acetoacetate in the perfusate was increased with palmitate at the end of perfusion at 37 degrees and 42 degrees C or octanoate at 42 degrees and 43 degrees C. Thus, long (palmitate)- and medium (octanoate)- but not short (acetate)-chain fatty acids enhance not only beta oxidation, but influence the redox state of hepatic mitochondria with an increase in the state of reduction of the pyridine nucleotides. Such a shift in the redox state would be operable in the perfused liver even at 43 degrees C and may be responsible for improved conversion of lactate to glucose when medium- or long chain fatty acids are present at hyperthermic temperatures. PMID- 4027948 TI - Constitutional C-band pattern in patients with adenomatosis of the colon and rectum. AB - The pattern of polymorphism in the C-band-positive constitutive heterochromatin of chromosomes #1, #9, and #16 was studied in fibroblasts from 23 unrelated patients with adenomatosis of the colon and rectum and in peripheral lymphocytes from 78 control persons. The parameters of the heterochromatic regions analyzed were relative size, symmetry-asymmetry within homologous chromosome pairs, and frequency of inversions. The polyposis coli patients had a significantly higher frequency (p less than 0.05) of partial and total heterochromatin inversion on chromosome #9 than the control group (37.0% compared with 21.8%). In the other parameters studied, no significant differences were found between patients and controls. PMID- 4027949 TI - C-band heteromorphism in breast cancer patients. AB - The pattern of heteromorphism in the C-band-positive constitutive heterochromatin of human chromosomes #1, #9, and #16 was studied in peripheral lymphocytes of 54 breast cancer patients and 78 control individuals. The parameters of the heterochromatic regions analyzed were relative size, symmetry-asymmetry within homologous pairs, and prevalence of inversions. Significant differences between the two groups were found in C-band size of chromosomes #1, #9, and #16 and in incidence of inversions on chromosomes #1 and #9. Significant differences were noted between premenopausal and postmenopausal cancer patients in regard to inversions on chromosome #9 and between familial and sporadic patients in regard to C-band size on chromosome #16. PMID- 4027950 TI - Double minutes in the HeLa cell line. AB - Metaphase preparations of three sublines of the HeLa line showed the presence of double minutes (DM) in varying frequencies. In two sublines (S3 and TCH-3753), the size of the DM was variable, whereas in the Fe-1000 subline, they were uniform. Giemsa banding preparations revealed typical HeLa marker chromosomes in all sublines. PMID- 4027951 TI - Uptake of 2-beta-D-ribofuranosylthiazole-4-carboxamide (tiazofurin) and analogues by the facilitated transport mechanism of erythrocytes. AB - Tiazofurin (TR), a new antitumor agent, enters human erythrocytes by utilizing their facilitated nucleoside transport system. TR competes with endogenous nucleosides for this transport mechanism, thereby reducing nucleoside uptake into the cells. Pre-incubation of erythrocytes for 10 min at 22 degrees C with 100 microM and 500 microM TR reduced the transport of 14C-uridine into the cells by 27% and 74%, respectively. Simultaneous exposure of cells to TR and [14C]uridine did not alter the inhibitory effect of TR. Furthermore, the transport inhibitory effect of TR was lost when cells were washed twice with Hanks basal salt solution following a 10-min pre-incubation with TR. The Km and Vmax (+/- S.E.) for radiolabeled TR transport into erythrocytes are 170 +/- 26 microM and 55 +/- 13 nmol/h per 10(6) cells, respectively, which is similar to the kinetic constants measured for uridine transport into erythrocytes (Km = 168 +/- 37 microM and Vmax = 61 +/- 16 nmol/h per 10(6) cells). The Ki (+/- S.E.) of TR for uridine transport is 178 +/- 11 microM and for thymidine transport is 102 +/- 59 microM. Three analogues of TR (its selenium isostere (SR), and Ara (Ara-TR) and Xylo (Xylo-TR) derivatives) were compared with TR for their ability to compete with and inhibit uridine transport, as these analogues were not available in a radiolabeled form for direct measurement of their transport into the cell. SR had similar kinetic characteristics of inhibition of uridine transport to TR (Ki = 145 +/- 15 microM) but Ara-TR had a Ki = 1.04 +/- 0.13 mM while Xylo-TR inhibited uridine transport with a Ki = 1.57 +/- 0.67 mM. Thus, TR is transported into erythrocytes with the same velocity and affinity for the carrier as uridine and competitively inhibits nucleoside transport into the cell. Of 3 other C nucleoside derivatives examined, SR is of similar potency to TR but Ara-TR and Xylo-TR are much less effective at competing with uridine for the nucleoside transporter. PMID- 4027952 TI - Photocytotoxicity in vivo of haematoporphyrin derivative components. AB - Phototoxicity of haematoporphyrin derivative (HPD) and some of its component porphyrins was assayed using Lewis Lung Carcinoma transplanted in C57BL mice. Skin photosensitivity was assessed by measuring percentage increase in footpad thickness after exposure to light. HPD and its aggregate fraction photosensitised the skin, was active in tumour destruction and caused fluorescence in the tumour while the non-aggregate fraction and pure haematoporphyrin were inactive, both in treatment of tumours and in sensitising the skin. The commercial product, Photofrin II was also photoactive and protoporphyrin was slightly active. It is concluded that the therapeutic activity of HPD is associated entirely with the aggregate fraction and compounds effective in tumour phototherapy also sensitise the skin. PMID- 4027953 TI - Dose-dependent persistence of alkylation-induced single stranded regions in rat liver DNA in vivo. AB - Single stranded regions in DNA, presumed to be indicative of DNA repair, may be readily detected in rat liver DNA following injections of non-necrotizing single doses of methyl methanesulfonate, dimethylnitrosamine and diethylnitrosamine. The present study concerns persistence of such structural defects in vivo, as determined by benzoylated DEAE-cellulose chromatography, in relation to the dose of alkylating agent. For all these agents, the period during which structural damage may be detected is markedly dependent upon dose: prolonged persistence only occurs after the highest dose. The findings, in relation to other data, implicate reaction processes involving the final stages of repair as being critical to prolongation of this type of genomic damage in vivo. PMID- 4027954 TI - Malic enzyme and malate dehydrogenase activities in rat tracheal epithelial cells during the progression of neoplasia. AB - Malic enzyme and malate dehydrogenase (MDH) activities were radiometrically assayed in digitonin fractionated normal primary cultures (NPC), preneoplastic selected primary cultures (SPC) and tumor-derived primary cultures (TPC) of rat tracheal epithelial cells. Carcinogen-altered SPC and TPC selectively grow in the absence of pyruvate, which is required by NPC for survival. Mitochondrial containing particulate fractions from TPC and especially SPC had markedly higher levels of NADP+-dependent malic enzyme than NPC in the presence or absence of pyruvate. This suggests that induction of mitochondrial malic enzyme activity occurs early in the progression of neoplasia. Malic enzyme activities in the soluble fractions from the various populations were not distinctly different. In contrast, particulate-bound MDH activity was higher in NPC and SPC than TPC in most cases, indicating a decrease in this enzyme late in tumorigenesis. PMID- 4027955 TI - Selenocystine is not a cystine antimetabolite in L1210 cells. AB - Selenocystine inhibited the growth in culture of murine L1210 leukemia cells to a greater extent when the cells were supplemented with a high concentration of cystine for optimal growth. Cells which grew suboptimally in a limiting cystine concentration were inhibited to a lesser extent. In this case, the time of onset of selenocystine inhibition coincided with the time of termination of growth at the lower cystine concentration. These observations are contrary to expectation for action of an antimetabolite, and it is concluded that selenocystine cannot be considered a cystine antagonist. PMID- 4027956 TI - The effects of the B16 malignant melanoma on induced inflammatory responses in host mice: inhibition of macrophage exudation. AB - C57BL6 mice were injected with B16F1 or B16F10 cells and granulocyte- or macrophage-rich inflammatory responses were subsequently induced. Analysis of cell yields showed that the percentages of macrophages in the inflammatory exudates of tumour-bearing animals were significantly depressed. No significant changes were noted, however, in the levels of granulocytes in peritoneal exudates from tumour-bearing mice when compared to appropriate controls. In parallel studies, the levels of resident macrophages and granulocytes following lavage of non-stimulated peritoneal cavities of mice with and without tumours were monitored as were the levels of blood monocytes and leukocytes. No consistently significant changes were noted in the levels of blood leukocytes or monocytes in normal or tumour-bearing animals. Furthermore, no consistently significant changes were found in the percentages of granulocytes normally resident in the peritoneal cavities of mice with or without the B16 melanoma. It was found, however, that the percentages of resident macrophages in mice bearing the B16 malignant melanoma were significantly depressed relative to those found in normal animals. PMID- 4027957 TI - DNA flow cytometry in human testicular cancer. AB - DNA flow cytometry revealed aneuploid tumour stemlines in 19 of 20 primary testicular cancers without significant difference of the ploidy values between seminomas and non-seminomas. In 7 of 8 analyzable histograms the S-phase activity was 22-51%. A metastatic mature teratoma had 6% cells in S-phase. These results support the clinical observation that testicular cancer is usually a rapidly growing human tumour. The high percentage of aneuploidy in testicular cancer may be of clinical value in the diagnosis of this malignancy. PMID- 4027958 TI - Antitumor effect of 6-phenyl-7(6H)-isoselenazolo[4,3-d]pyrimidone on the growth of Ehrlich ascites tumor. AB - Two selenium compounds have a strong antitumor effect on Ehrlich ascites tumor; 6 phenyl-7(6H)-isoselenazolo[4,3-d]pyrimidone (ISP) especially, markedly inhibited the growth of tumor inoculated i.p. in mice, inducing almost complete regression of tumors at doses of 100 micrograms/mouse per day X 10 with no sign of toxicity. The antitumor activity of 4,5-dihydro-4-methyl-6-oxo-5-phenyl-6H-pyrazolo [4,5 c]isoselenazole(PIS) was weaker than that of ISP. The total lipid and phospholipid contents in the tumor cells treated with ISP were significantly decreased. In addition, the fatty acid pattern of cholesterol esters, phosphatidyl choline and phosphatidyl ethanolamine from the ISP-treated Ehrlich ascites tumor cells differed markedly from that of the corresponding lipids from the control tumor cells. PMID- 4027959 TI - Zeranol (beta-resorcylic acid lactone), a common residous component of natural foodstuffs, stimulates developmental growth of the mouse mammary gland. AB - ICR mice ovariectomized at 6 weeks of age were divided into 5 groups and injected s.c. daily for 20 days with: (1) 0.9% NaCl solution containing 0.1 mg/ml gum arabic (controls); (2) zeranol (Z) (1.0 microgram/day); (3) progesterone (P) (1.0 mg/day); (4) Z + P or (5) 17 beta-estradiol (1.0 microgram/day) + P (E + P). Mammary gland (no. 4, inguinal) growth was assessed by analysis of mammae wet weight, dry fat free weight, DNA content and mammae whole mount evaluation. Administration of Z, alone or in combination with P, increased all 4 measures of mammary growth (P less than 0.05). The combination of Z + P was highly mammogenic, with mammary wet weight, dry weight and DNA content comparable to that obtained with E + P. Mammae development scores of Z + P treated mice were only slightly less than those from E + P treated mice. The mammary glands of Z treated mice had increased duct number (branching) and thickening. The glands of Z + P treated mice had extensive duct branching with occasional lobule-alveolar development. These data indicate that Z, alone or in combination with P, is an effective mammogen possessing mammogenic properties similar to the potent natural estrogen 17 beta-estradiol. PMID- 4027960 TI - In vitro transformation of BALB/c-3T3 cells by chlorinated ethanes and ethylenes. AB - Eight chlorinated ethanes and 3 chlorinated ethylenes were tested in the BALB/c 3T3 cell transformation assay. Under the conditions of the assay, vinyl chloride and 1,1,1-trichloroethane induced a clear positive transformation response while 1,1,2-trichloroethane and trichloroethylene were weakly positive. Chloroethane, 1,1- and 1,2-dichloroethane, 1,1,1,2- and 1,1,2,2-tetrachloroethane, hexachloroethane and tetrachloroethylene were all negative in the assay conducted in the absence of an exogenous metabolic activation system. These results suggest that the BALB/c-3T3 cells possess capability to activate some, but not all, of the chlorinated hydrocarbons which exhibit species specificity in producing carcinogenicity in mice but not in rats. PMID- 4027961 TI - Depletion of extracellular cysteine with hydroxocobalamin and ascorbate in experimental murine cancer chemotherapy. AB - Treatment of mice bearing P388 lymphocytic leukemia with combined hydroxocobalamin (0.1 mmol/kg) and sodium ascorbate (1.0 mmol/kg) for 10 consecutive days resulted in 70% increase in survival. Treatment with dehydroascorbate (1.0 mmol/kg) similarly increased survival. The extended treatment for 15 days posttumor inoculation failed to improve survival as did lowering the tumor inocula from 10(6) to 10(4) cells in similarly treated mice. P388 cells in primary culture with cystine as a source of cysteine require exogenous thiols or disulfides for growth and also grow with cysteine but only when trace copper is sequestered with bathocuproine sulfonate. This is due to the copper catalyzed oxidation of cysteine to cystine, which these cells cannot utilize. Cells grew in medium preincubated for 8 h with cysteine and bathocuproine sulfonate, but lysed when the preincubated medium included hydroxocobalamin (10 microM) and sodium ascorbate (100 microM). This defect was corrected by resupplementation with cysteine or cystine plus bishydroxyethyl disulfide after addition of the cells. Further support for cysteine depletion as a factor in therapy is obtained by therapeutic interference with 4-thiamethionine (25 mumol/kg). This mixed disulfide of cysteine and methyl mercaptan enters cells as a methionine analogue, is reduced to supply cysteine, and thus withstands the oxidative environment that limits the utilization of cysteine as a nutrient. These results suggest that dehydroascorbate is generated from combined hydroxocobalamin and ascorbate and accounts for the thiol-prive activity of combined hydroxocobalamin and ascorbate therapy. The ultimate failure of therapy by thiol oxidation may be due to the increased availability of cysteine produced by host tissues, possibly infiltrating macrophages, that occurs independently of extended treatment and the size of the tumor inoculum. PMID- 4027962 TI - Characterization of L1210 cell growth inhibition by the bacterial iron chelators parabactin and compound II. AB - Microbial siderophores represent a class of iron chelators characterized by their high affinity (i.e., formation constants, greater than 10(40) M) for ferric iron. Previously, we demonstrated that the bacterial siderophores, N-[3-(2,3 dihydroxybenzamido)propyl]-N-[4-(2, 3-dihydroxybenzamino)butryl]-2-(2 hydroxyphenyl) trans-5-methyloxazoline-4-carboxamide (Parabactin) and N1,N8 bis(2,3-dihydroxybenzoyl)spermidine (Compound II), inhibit the growth of L1210 cells and the replication of DNA (but not RNA) viruses at low micromolar concentrations (Biochem. Biophys. Res. Commun., 121: 848-854, 1984). The basis for this antiproliferative effect on L1210 cells has now been investigated further. Onset of growth inhibition induced by 5 microM Parabactin occurs much earlier than with an equimolar concentration of Compound II but, once established by either chelator, inhibition appears to be irreversible. Growth inhibition was fully preventable with exogenous FeCl3 when given at the same time as the chelators. Flow cytometric analysis revealed a G1-S cycle block following treatment for 4 h with either 5 microM Parabactin or 30 microM Compound II. The block was readily reversed with exogenous FeCl3, allowing cells to progress to mid-S phase by 3 h and to G1 again by 9 h. Thereafter, cells accumulated at a second block located at S phase. The treatment conditions required for the initial cell cycle block (at 4 h) were adapted for subsequent studies. Clonogenicity of L1210 cells in soft agar following a 4-h exposure was reduced to 22% of control by 5 microM Parabactin and to 16% by 30 microM Compound II. Neither growth inhibition in suspension culture nor decreased clonogenicity in soft agar could be reversed with exogenous iron, following treatment with the chelators. Both chelators caused an early and significant decrease in [14C]thymidine incorporation over the 4-h period (50% inhibitory concentration at 4 h, 0.4 microM for Parabactin and 6.0 microM for Compound II). [3H]Uridine incorporation was inhibited later than [14C]thymidine and to a much lesser extent, while [3H]leucine incorporation was not significantly affected. Treatment of cells with 5 microM Parabactin or Compound II for 4 h decreased deoxy adenosine triphosphate pools by 38 and 70%, respectively, and increased deoxythymidine triphosphate pools by 67 and 36%, respectively, suggesting interference with ribonucleotide reductase. Indeed, extracts of cells treated for 4 h with either 5 microM Parabactin or 30 microM Compound II exhibit a 97 to 98% decrease in cytidine-5'-diphosphate reductase activity compared to control, whereas DNA polymerase was elevated slightly.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 4027963 TI - Effect of gastrin on gastric mucosal cyclic adenosine 3':5'-monophosphate dependent protein kinase activity in rat stomach carcinogenesis induced by N methyl-N'-nitro-N-nitrosoguanidine. AB - This was a study of the effects of gastrin on gastric mucosal cyclic-adenosine 3':5'-monophosphate (cAMP)-dependent protein kinase activity and DNA synthesis in rat stomach carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) in order to clarify the mechanism of the enhanced effect of gastrin on the early stage of stomach carcinogenesis. Inbred Basel-Wistar rats received MNNG in drinking water (50 micrograms/ml for 32 weeks) and were treated with s.c. injections of pentagastrin (300 micrograms/kg twice daily for 4 weeks) beginning with the fourth and eighth weeks after the initiation of MNNG treatment. The incidence of gastric adenocarcinoma in fourth-week gastrin-treated rats and of gastric carcinoid in eighth-week gastrin-treated rats was higher than that in rats treated with MNNG alone. The former tumors developed in the antrum and most of the latter tumors in the fundus. In the early stage of carcinogenesis the labeling index [( 3H]thymidine-labeled nuclei/one gland) in both the antrum and fundus was the same in MNNG-plus-gastrin-treated groups and in the MNNG-only treated group. With regard to the distribution of cAMP-dependent protein kinase isoenzyme in fourth-week gastrin-treated rats, the proportion of type I cAMP dependent protein kinase significantly increased in the antrum during the eighth week after the initiation of MNNG treatment (P less than 0.01). The increased type I activity in the antrum of the gastrin-treated rats agreed with the high incidence of gastric adenocarcinoma in the antrum. Type I isoenzyme clearly increased in gastric adenocarcinoma. These results suggest that type I cAMP dependent protein kinase can play an important role in the enhanced effect of gastrin on rat stomach carcinogenesis induced by MNNG. PMID- 4027964 TI - Modulation of repair of O6-methylguanine in parenchymal and nonparenchymal liver cells of rats treated with dimethylnitrosamine. AB - Previous studies have shown that chronic treatment of rats with dimethylnitrosamine (DMN) (2 mg/kg for 3 weeks) results in increased repair of O6 methylguanine (O6-mGua) in liver DNA. The experiments reported here try to determine if this increased repair is confined to one or more cell populations of the liver. Liver cells [parenchymal (PC) and nonparenchymal (NPC)] were separated by elutriation centrifugation at various times after the last administration of DMN. The in vivo alkylation studies show that at any time after a dose of [14C]DMN (2 mg/kg) the level of O6-mGua in PC cells of DMN pretreated rats was much lower than in the same cell population from control rats receiving only a single dose of DMN. In contrast, the pretreatment schedule resulted in no change in the levels of this DNA adduct in NPC cells. These results were confirmed by the determination of the levels of O6-methyldeoxyguanosine by radioimmunoassay in DNA from PC or NPC cells of rats similarly either pretreated for 3 weeks with DMN or receiving a single dose of DMN (2 mg/kg). The in vitro measurements of O6-mGua DNA alkyltransferase activity, using alkylated DNA as substrate, also show a higher activity of this repair enzyme in PC cells. The DMN pretreatment resulted in a 25-fold difference in O6-mGua DNA alkyltransferase activity between the two cell populations of the liver. PMID- 4027965 TI - In vivo augmentation of rat lung natural killer cell activity and inhibition of experimental metastases by double-stranded polynucleotides. AB - The in vivo effect on natural killer cell activity of the compound rln X r(C12 X U)m, a mismatched nontoxic analogue of polyinosinic-polycytidylic acid [rln X rCn], was tested in inbred Wistar AG rats by measuring the natural killer cell activity of lymphocytes freshly isolated from lung capillaries. Lysis was measured in a 4-h chromium release assay using YAC-1 or syngeneic P77 lung tumor cells as target. Treatment of an animal with rln X r(C12 X U)n substantially enhanced natural killer cell activity to an extent comparable to the increase produced by rln X rCn. This boosting of natural killer activity was correlated closely with a decrease in the incidence of experimental pulmonary metastasis. However, the beneficial effect lasted for only a short period after stimulation, due to the transient nature of double stranded polynucleotide enhancement and to the concomitantly rapid extravasation of tumor cells into the lung parenchyma. It is concluded that natural killer cells are important in host defense against circulating tumor cells and can be boosted by nontoxic mismatched double stranded polynucleotides. PMID- 4027966 TI - Relationships of prostaglandin E and natural killer sensitivity to metastatic potential in murine mammary adenocarcinomas. AB - The levels of two prostaglandins (prostaglandins E and F) have been determined in a series of murine mammary lesions ranging from preneoplastic, hyperplastic alveolar nodules to highly metastatic adenocarcinomas. A highly positive correlation was seen between high levels of prostaglandin E and high tumorigenicity and metastatic potential. In addition, spontaneous metastasis of two highly metastatic tumors was partially inhibited by p.o. administration of indomethacin from the time of s.c. tumor transplantation until removal of the primary tumor at a limited size. Further, mammary tumor cells of differing metastatic potential were susceptible to polyinosinic-polycytidylic acid activated spleen lymphocytes in vitro. Cells of metastatic tumor lines (410.4 and 66) were more resistant to killing than were cells of two non-metastatic tumor lines (168 and 410). The sensitivity of all target cells was increased when endogenous prostaglandin synthesis was prevented by the addition of indomethacin (1 microM) but was not affected by the lipoxygenase inhibitor nordihydroguaiaretic acid. PMID- 4027967 TI - Mechanism of estrogen enhancement in the growth of androgen-dependent Shionogi carcinoma 115. AB - The mechanism of estrogen enhancement in the growth of androgen-dependent Shionogi carcinoma 115 (SC115) maintained in castrated DS mice by low doses of androgen (10 micrograms of testosterone propionate or 4 micrograms of 5 alpha dihydrotestosterone/mouse/day) is reported. Although the low androgen treatment slightly but significantly (P less than 0.05) stimulated tumor growth, concomitant estrogen (4 micrograms of 17 beta-estradiol/mouse/day) significantly (P less than 0.01) enhanced the tumor growth. The high growth rate, histological type (medullary carcinoma), androgen dependency, and high androgen receptor content of the tumor grown during estrogen plus low androgen treatment did not differ significantly from those of the original SC115 tumor grown in normal males or in castrated mice treated with high doses of androgen. On the other hand, the treatment with low doses of androgen alone induced the development of slowly growing spindle-shaped cells from the medullary SC115 cells. The spindle-shaped cells containing low levels of androgen receptor were shown to be androgen independent and were also induced from the SC115 cells in nontreated castrated mice. These findings demonstrated that low doses of androgen and estrogen synergize to maintain and increase the growth of SC115 cells, whereas low doses of androgen alone fail to maintain the SC115 cells. PMID- 4027968 TI - Thermal sensitivity to single and double heat treatments in normal canine liver. AB - The treatment of intrahepatic or perihepatic neoplasms by hyperthermia may be limited by the thermal sensitivity of normal liver tissue. To establish the temperature dependence of hepatic toxicity, eight canine liver lobes were exposed to a single 30-min dose of localized hyperthermia in the range of 43.0 degrees C 47.5 degrees C, induced by radiofrequency currents. Four additional liver lobes were conditioned with a pretreatment dose of 43.0 degrees C/30 min and challenged at either 44.5 degrees C/30 min or 47.5 degrees C/30 min, 4 h later. Temperature distributions were measured using implantable thermocouple sensors. Treated areas were sampled 28 days later, and liver damage was determined using histopathological criteria. Most treated sites showed only modest alterations. The parameters of tissue injury that correlated best with dose were: evidence of hepatocyte loss; focal fibrosis; and distortion of lobular architecture. Areas of necrosis were observed in several samples, but their presence or severity did not correlate with dose. Thermal damage to liver capsule, liver lobules, portal areas, and central veins did not exhibit monotonic dose-response relationships. The data do not demonstrate thermotolerance; in fact, they suggest, although do not prove, its absence. If thermotolerance did not develop, vascular effects might explain such a finding. PMID- 4027969 TI - N-Methyl-N-nitrosourea potentiation of cytogenetic damage induced by 1,3-bis(2 chloroethyl)-1-nitrosourea in normal human lymphocytes. AB - DNA repair of O6-alkylguanine by O6-alkylguanine-DNA alkyltransferase (O6-AT) may be crucial in modulating the extent of cytogenetic damage induced by 1,3-bis(2 chloroethyl)-1-nitrosourea (BCNU), an important anticancer chemotherapeutic agent. To test this idea we treated normal human lymphocytes for 1 h with methylnitrosourea (MNU), which inactivates O6-AT, and then treated them for 1 h with BCNU. The result was a synergistic increase in the number of sister chromatid exchanges (SCEs) and chromosomal aberrations induced. BCNU-induced SCEs were potentiated 1.4- to 2.5-fold in MNU-pretreated cultures. Pretreatment of lymphocytes with MNU resulted in a 4- to 28-fold increase in the number of BCNU induced chromatid aberrations. The enhancement of both SCEs and aberrations induced was MNU-dose dependent. Treatment of lymphocytes with MNU alone did not affect cell cycle progression, suggesting that MNU does not influence the extent of BCNU-induced cytogenetic damage by selecting highly damaged cells through alterations in lymphocyte proliferation kinetics. The potentiation of SCE and aberration induction by pretreatment with MNU is postulated to be due to inhibition of O6-AT. This inhibition would permit the formation and persistence of BCNU-induced O6-(2-chloroethyl)guanine monoadducts, which can undergo subsequent reactions to form DNA cross-links. In humans variations in O6-AT resulting from acute alkylation exposure or genetic deficiency may be important in modulating the genotoxic effects of BCNU. PMID- 4027970 TI - Metabolic fate of liposomal phosphatidylinositol in murine tumor cells: implications for the mechanism of tumor cell cytotoxicity. AB - The mechanism of the previously reported cytotoxicity of liposomes containing plant phosphatidylinositol (PI) against numerous tumor cell lines was examined in detail by using liposomes containing synthetic PI specifically labeled either with radioactive myo-inositol, or in the sn-2 position with radioactive linoleic acid, oleic acid, or arachidonic acid. The uptake of liposomal PI by N4TG1 neuroblastoma cells increased with time and was dependent on the nature of the fatty acids. Uptake was highest with liposomal PI containing linoleic acid followed by arachidonic acid and then by oleic acid. The cellular fate of liposomal PI was determined by analysis of radioactive metabolites present in extracts of tumor cell lipids. Appearance of liposomal PI metabolic products in the tumor cells was correlated with thymidine uptake as a measure of viability. After 3 h incubation of cells with PI liposomes it was found that the release of both radioactive liposomal fatty acids (and probably also lyso-Pl) and radioactive diglycerides was correlated inversely with the cellular uptake of [methyl-3H]thymidine and uptake of [3H]myoinositol. An experiment in which liposomes were prepared both from animal Pl which contained predominantly saturated fatty acids in the sn-2 position and an increasing mole fraction of a synthetic Pl containing radioactive linoleic acid in the sn-2 position established that the amount of Pl containing linoleic acid in the sn-2 position could be correlated with a decrease in the amount of thymidine uptake by tumor cells. The above results clearly established that phospholipases A2 and C in the tumor cells were responsible for the formation of metabolites of liposomal Pl, and these metabolic products might have been responsible for cytotoxicity and cell death. PMID- 4027971 TI - Chromosome damage induced by vinyl acetate through in vitro formation of acetaldehyde in human lymphocytes and Chinese hamster ovary cells. AB - A 48-h treatment with vinyl acetate (0.05-1 mM) induced a drastic increase in sister chromatid exchanges (SCEs) and (in first division cells) structural chromosome aberrations in cultured human lymphocytes. The effects were more pronounced in cultures of isolated lymphocytes than in whole-blood cultures. A distinct dose-dependent induction of SCEs similarly occurred in Chinese hamster ovary cells after a 24-h vinyl acetate treatment (0.125-1 mM). A pulse treatment of Chinese hamster ovary cells for 4 h also yielded a clear increase in SCEs, but at higher concentrations (0.3-5 mM). The presence of rat liver S9 mix enhanced the SCE-inducing effect of vinyl acetate in Chinese hamster ovary cells. Gas chromatographic analysis of human whole-blood lymphocyte cultures treated for 10 s-20 min with vinyl acetate (5.4 mM) revealed a rapid degradation of vinyl acetate and formation of acetaldehyde. During the 20-min observation period, no degradation of vinyl acetate or formation of acetaldehyde were observed in complete culture medium without blood, which suggested that the reaction was enzymatic. Acetaldehyde induced SCEs in human whole-blood lymphocyte cultures at concentrations (0.125-2 mM) comparable to those used for vinyl acetate. The results indicate that vinyl acetate induces chromosome damage in cell cultures through enzyme-mediated hydrolysis to acetaldehyde. PMID- 4027972 TI - Synergistic interaction between hydroquinone and acetaldehyde in the induction of sister chromatid exchange in human lymphocytes in vitro. AB - Hydroquinone, a metabolite of benzene, and acetaldehyde, a metabolite of ethanol, induce sister chromatid exchanges (SCEs) at relatively high concentrations. Because both compounds are reported to form glutathione conjugates, experiments were carried out to see if there was a synergistic effect when lower concentrations of both chemicals were added to human lymphocyte cultures. Hydroquinone (40 microM) increased SCEs in some individuals but not in others. However, the rate of SCE was more than doubled when cells were pretreated with diethyl maleate, which transiently depletes cellular glutathione. Acetaldehyde by itself increased SCEs at 100 microM, but it increased SCEs at 1 microM in the presence of diethyl maleate. When various concentrations of acetaldehyde were added to cultures containing 40 microM hydroquinone, synergism in the induction of SCEs was observed. The lowest effective concentration of acetaldehyde varied among individuals from 1 to 100 microM. These observations suggest that glutathione is involved in the detoxification of hydroquinone and acetaldehyde in lymphocytes and that the simultaneous presence of both chemicals may saturate this mechanism and thus increase their genotoxic potency. Genetic differences in glutathione metabolism may govern the concentration of acetaldehyde at which synergism occurs in different individuals. PMID- 4027973 TI - Association of DNA strand breaks with accelerated terminal differentiation in mouse epidermal cells exposed to tumor promoters. AB - We have studied the appearance of single strand breaks (SSB) in DNA of mouse keratinocytes exposed in vitro to various tumor promoters. Mouse basal keratinocytes were selectively cultured in low calcium medium, prelabeled with [14C]thymidine, exposed to test agents, and SSB quantified by alkaline elution. 12-O-Tetradecanoylphorbol-13-acetate (TPA) caused a dose-dependent (10(-9)-10(-7) M) increase in SSB after 24 h but not after shorter exposures. DNA containing TPA induced SSB was found only in cells which had detached from the culture plate as a consequence of TPA-induced terminal differentiation. Attached cells, resistant to the differentiation-inducing effects of TPA, had the low level of SSB found in DNA from vehicle-treated control cells. Attached cells were resistant to the formation of SSB and to induced differentiation when reexposed to TPA. Other tumor-promoting phorbol esters, mezerein and retinyl phorbol acetate, also produced SSB in detached cells, whereas phorbol or resiniferatoxin caused neither SSB or cell detachment. Retinoic acid, which blocks the induction of differentiation by TPA, inhibited the production of SSB by TPA; however, fluocinolone acetonide, chymostatin, catalase, or superoxide dismutase blocked neither TPA-induced SSB nor terminal differentiation. Epidermal cell lines resistant to TPA-induced differentiation were also resistant to SSB production by TPA. Benzoyl peroxide (BP) (10(-4) M) induced SSB in basal keratinocytes within 1 h, and attached cells showed extensive SSB by 12 h. Retinoic acid had only a slight effect on BP-induced SSB, and 1 of 3 TPA-resistant cell lines developed SSB when exposed to BP. These results suggest that TPA-induced SSB in epidermal cells are an indirect consequence of the induction of terminal differentiation, whereas BP produces SSB by a more direct mechanism of DNA damage. PMID- 4027974 TI - Tissue nitrogen-sparing effect of high protein diet in mice with or without ascites tumor treated with Acinetobacter glutaminase-asparaginase. AB - Forty-eight tumor-free mice and 32 mice bearing Ehrlich ascites tumor were randomized into 2 treatments, Acinetobacter glutaminase-asparaginase (AGA) (600 IU/kg/day for 7 days) and 0.9% NaCl controls, and into 2 or 3 isocaloric diets, normal protein (NP) (20 g protein/100 g diet), high protein (HP) (58 g protein/100 g diet), and zero protein (ZP) (tumor-free mice only). In tumor-free, NP-fed mice, AGA caused percentage reductions (P less than 0.01) in the nitrogen content of liver (50%), intestine (42%), thymus (89%), spleen (75%), and carcass (20%), but HP prevented this effect on intestine and carcass and caused percentage increases in the nitrogen content of liver (53%), intestine (36%), thymus (122%), and carcass (25%). In Ehrlich ascites tumor mice (NP or HP fed) AGA caused markedly lower (P less than 0.01) tumor burdens and increased nitrogen content of intestine (HP), kidney (NP and HP), and spleen (NP and HP). Ehrlich ascites tumor, AGA-treated, HP-fed mice ate 31% less food (P less than 0.01) (compared to NP) but HP resulted in percentage increases in the nitrogen content of liver (18%; P = 0.05), intestine (25%; P less than 0.05), and thymus (164%; P less than 0.01). In the Ehrlich ascites tumor, AGA group the HP diet caused higher hematocrit and serum total protein (both, P less than 0.05). Adverse nutritional effects of AGA seen in normal mice were markedly diminished in tumor bearing animals. The observed nitrogen-sparing effects of the high protein: energy ratio may be relevant to humans and to other forms of neoplasia and chemotherapy. PMID- 4027975 TI - Inhibition of Leydig tumor cell steroidogenesis by 10-propargylestr-4-ene-3,17 dione, an irreversible aromatase inhibitor. AB - The murine Leydig cell tumor (M5480A) was assayed for the presence of aromatase activity and for the effects of 10-propargylestr-4-ene-3,17-dione (PED), an aromatase inhibitor, on steroidogenesis. Microsomal preparations from these tumors contained low levels of aromatase activity which was PED sensitive. In addition, these Leydig tumor cells were maintained in primary culture and incubated under basal and gonadotropin-stimulated conditions with various doses of PED. Medium levels of progesterone, a major product of these cells, were found to decrease in a dose- and time-dependent manner upon addition of PED. To determine whether the observed effect was due to reduced synthesis or to increased metabolism of progesterone, tritiated progesterone was added to these cell cultures. Analysis of culture medium by high-performance liquid chromatography suggested that PED dramatically reduced the conversion of labeled progesterone to testosterone. Furthermore, examination of medium pregnenolone levels revealed diminished amounts of this steroid as well. Taken together, these results suggest that PED or its metabolites inhibit Leydig tumor cell steroidogenesis at several sites. Thus, in addition to its role as an aromatase inhibitor, this agent also has effects prior to pregnenolone production, as well as other effects in the pathway between progesterone and testosterone. PMID- 4027976 TI - Effects of thermal adaptation at 40 degrees C on membrane viscosity and the sodium-potassium pump in Chinese hamster ovary cells. AB - We have demonstrated increased heat resistance in Chinese hamster ovary cells grown to confluence at 37 degrees C and thermally adapted at the nonlethal temperature of 40 degrees C for 24 h. Membrane viscosity, estimated by fluorescence anisotropy, was inversely related to temperature, from 5 degrees C to 45 degrees C. For a given temperature viscosity was consistently higher in thermally adapted cells than in native cells. Having demonstrated a change in membrane structure associated with thermal adaptation, we carried out a study of the Na+-K+ pump in native and thermally adapted cells as an example of a vital active transport process known to be sensitive to membrane viscosity. 86Rb uptake measured from 31 degrees C to 50 degrees C increased steadily to 46 degrees C and then decreased rapidly in both native and thermally adapted cells. Detailed measurement of ouabain-sensitive 86Rb influx demonstrated an increase in both Km and Vmax between 37 degrees C and 45 degrees C, but there was no difference between native and thermally adapted cells. We have thus demonstrated an adaptive structural change in the cell membrane of mammalian cells which may be related to the induction of thermal resistance at 40 degrees C but which is not associated with any change in this active transport system. PMID- 4027977 TI - Depletion of cellular glutathione by exogenous spermine in V79 cells: implications for spermine-induced hyperthermic sensitization. AB - The relationship between spermine-induced thermosensitization and modulation in the cellular redox state as measured by glutathione levels was studied using Chinese hamster V79 cells. Marked cellular glutathione depletion was observed for cells treated with exogenous 1 mM spermine at 37 degrees C or 43 degrees C. Glutathione depletion and thermal sensitization by spermine were found to be cell density dependent with maximum depletion and sensitization observed at low cell densities. These findings are discussed in the context that treatment of cells with exogenous polyamines such as spermine can result in cellular oxidative stress which may in part contribute to spermine-induced thermal sensitization. PMID- 4027978 TI - Comparative molecular pharmacology in leukemic L1210 cells of the anthracene anticancer drugs mitoxantrone and bisantrene. AB - 1,4-Dihydroxy-5,8-bis(2-[(2-hydroxyethyl)aminoethyl]amino)-9, 10-anthracenedione (mitoxantrone) and 9,10-anthracenedicarboxaldehyde bis[(4,5-dihydro-1H-imidazol 2y)hydrazone] dihydrochloride (bisantrene) were evaluated for their abilities to cause cytotoxicity and interact with cellular DNA using leukemic L1210 cells. On a molar basis mitoxantrone has been found to be 7-fold more toxic than bisantrene. Using a nucleoid sedimentation technique, bisantrene caused changes in DNA supercoiling which were characteristic of an intercalating drug, but mitoxantrone did not induce these changes. Both drugs were found to interact with cellular DNA with tight but noncovalent binding. Both drugs also induced protein associated double- and single-strand DNA breaks, but with mitoxantrone only some of the DNA single-strand breaks were protein associated, whereas with bisantrene all the DNA single-strand breaks were protein associated. The cytotoxicity produced by bisantrene at a given frequency of protein-associated DNA strand breaks was low. However, with mitoxantrone at an equivalent DNA strand break frequency, the cytotoxicity was high. Treatment of isolated L1210 nuclei with either drug did not result in DNA single-strand breaks. It can be concluded that bisantrene binds DNA in whole cells by an intercalative mechanism, whereas mitoxantrone binds DNA by a nonintercalative, electrostatic interaction and induces non-protein-associated DNA strand breaks. PMID- 4027979 TI - Some characteristics of the cyclophosphamide-induced immunopotentiating cells in the spleen of mice bearing a large MOPC-315 tumor. AB - We have shown previously (Ye, Q-W., and Mokyr, M. B. Cancer Res., 44: 3873-3879, 1984) that, following low-dose cyclophosphamide (CY) therapy (15 mg/kg) of mice bearing a large s.c. MOPC-315 tumor and extensive metastases, T-cell-dependent immunopotentiating activity appears in their hitherto immunosuppressive Sephadex G-10-adherent spleen cell population. Here we show that the CY-induced immunopotentiating T-cells express the Lyt 1, Lyt 2, and L3T4 phenotypes. The phenotype of the immunopotentiating T-cells was deduced from our observations that depletion of Lyt 1+, Lyt 2+, or L3T4+ cells from the Sephadex G-10-adherent spleen cell population of CY-treated tumor bearers abolished the ability of the adherent cells to enhance the generation of antitumor cytotoxicity when added to the in vitro immunization culture of normal spleen cells. Moreover, admixture of a Sephadex G-10-adherent cell population depleted of Lyt 2+ cells with a Sephadex G-10-adherent cell population depleted of L3T4+ cells failed to restore the immunopotentiating activity, indicating that T-cells that are apparently expressing simultaneously the Lyt 2 and L3T4 antigens are required for the exertion of the CY-induced immunopotentiating activity. The CY-induced immunopotentiating T-cells from MOPC-315 tumor bearers brought about the appearance of enhanced antitumor cytotoxicity not only against the MOPC-315 tumor cells, but also against two other syngeneic plasmacytomas, with surface immunoglobulin of a different class and antigenic specificity than the MOPC-315 tumor cells, as well as against a variant MOPC-315 tumor line which lacks surface immunoglobulin. The CY-induced immunopotentiating T-cells did not enhance the appearance of antitumor cytotoxicity against a syngeneic (WEHI 22.1) or an allogeneic (EL4) tumor of T-cell origin nor against the natural killer-sensitive YAC-1 cells. Thus, L3T4+, Lyt2+ T-cells from CY-treated MOPC-315 tumor bearers enhance the generation of antitumor cytotoxicity that is directed against plasmacytoma shared antigens other than immunoglobulins. PMID- 4027980 TI - Evaluation of growth and histology of human tumor xenografts implanted under the renal capsule of immunocompetent and immunodeficient mice. AB - Fresh surgical explants of human carcinomas were implanted as first transplant generation xenografts under the kidney capsule of mice. Immunocompetent and immune-deficient mice were compared for their ability to support the persistence and growth of these xenografts. Consistent growth of tumor xenografts could not be demonstrated following implantation under the kidney capsule of immunocompetent mice. Immunological infiltration and rejection of the xenografts began 3 days postimplantation, and tumors were largely eliminated from the subcapsular space by 6 days postimplantation. In contrast human tumors consistently grew under the kidney capsule of nude mice. Significant growth became apparent by 9 days postimplantation with most human carcinomas and continued thereafter. Growth was always accompanied by neovascularization of tumor xenografts which was visible by examination of tumor-bearing kidneys under a dissecting microscope (X 6). There was no histological evidence of immunological interference with the persistence and growth of xenografts in nude mice. Thymectomized, irradiated, bone marrow-reconstituted conventional mice, as well as conventional mice, treated daily with 60 mg of cyclosporine A/kg were comparable to nude mice as hosts which supported the long-term persistence and growth of subrenal capsule implants of human tumors. Such mice could provide an alternative to nude mice as hosts in which chemosensitivity assays could be carried out against growing human tumors at a considerable saving in cost and convenience. PMID- 4027981 TI - Characterization of mammalian phosphoribosylglycineamide formyltransferase from transformed cells. AB - Phosphoribosylglycineamide formyltransferase levels were studied in several mammalian tissues and were found to be elevated 3- to 6-fold in some anaplastic cells, including rat hepatoma H-35 and mouse leukemia L1210, as compared to their corresponding normal tissues. The enzyme was found to reside in the cytosol of chicken liver and L1210 cells. The enzyme was purified to near homogeneity, as judged by a single band on polyacrylamide gels after electrophoresis in the presence of sodium dodecyl sulfate, from two mammalian sources, mouse L1210 and mouse Sarcoma 180. Comparison of the digestion patterns of L1210 enzyme and chicken liver enzyme upon exposure to chymotrypsin showed some similarity between the two, as did cross-reactivity in Western blots of the chicken enzyme with antibodies raised to the L1210 enzyme. Subunit molecular weight of the L1210 and Sarcoma 180 phosphoribosylglycineamide formyltransferases is about 117,000. Steady-state kinetics was performed with the purified murine enzyme in the presence of 5'-phosphoribosyl-N-glycineamide and 10-formyltetrahydrofolate and with 5'-phosphoribosyl-N-glycineamide and 10-formyl-5,8-deazafolate, establishing that these mammalian enzymes utilize 10-formyltetrahydrofolate as the actual cofactor. 11-Formyltetrahydrohomofolate was found to be an inhibitor of the murine and human (HeLa) enzymes, competitive with respect to 10 formyltetrahydrofolate, with KiS of 1 and 3 microM, respectively. 11 Formyldihydrohomofolate was an inhibitor of HeLa cell growth with a 50% effective dose of 8-11 microM. PMID- 4027982 TI - Polar solvent-induced changes in membrane lipid lateral diffusion in human colon cancer cells. AB - Polar organic solvents, such as N-methylformamide (NMF), N,N-dimethylformamide, and dimethyl sulfoxide, have been demonstrated to induce differentiation in a number of neoplastic cell lines, including human colon cancer cells. Although the mechanism of action of these agents is yet unknown, one possibility is that polar solvents induce a change in lateral mobility of membrane lipids, important to the maturational process. To determine the relationship between polar solvent treatment and changes in membranes, we examined the effects of exposure to NMF on membrane fluidity in human colon cancer cells (DLD-1; clone A). Membrane viscosity was assessed by determining lipid lateral diffusion following photobleaching of a fluorescent lipid probe in individual intact cells. Exposure of cells to NMF led to a significant increase in membrane viscosity following 2 days of treatment, with maximal changes occurring after 11 days. NMF induced these effects over a limited concentration range with 1.0% NMF in the medium having the maximal effect, and 0.5% or 1.5% having less or no effect. Growth of cells with N,N-dimethylformamide (0.8%) also led to increases in membrane viscosity. The observed membrane changes correlated well with the effect of NMF on differentiation in these cells as previously reported, as well as with cell growth rate and morphology in the present study. The increase in viscosity caused by prolonged NMF treatment was reversible, with a return to untreated levels by 9 11 days after removal of NMF. Thus, there is a strong correlation between the attainment of more benign, better differentiated phenotype in polar solvent treated clone A cells and increases in membrane viscosity. PMID- 4027983 TI - Identification of a tumor cell-derived differentiation antigen on mouse colony forming units in the spleen and progenitor cells. AB - Surface membrane antigen(s) expressed on a mouse mast cell line (FMP1) have also been shown to occur on hemopoietic spleen colony-forming units (CFU-S) and granulocyte/macrophage colony- and erythroid burst-forming cells, using a xeno antiserum raised against FMP1 cells. This mast cell model has been used to obtain antiserum and large quantities of antigen for the biochemical identification of CFU-S and progenitor cell antigen(s). Immunoprecipitation of FMP1 membrane antigens with the antiserum and subsequent polyacrylamide gel electrophoresis revealed the presence of five membrane proteins with molecular weights of 28,000, 32,000, 36,000, 50,000, and 70,000. Mouse B-lymphoma cell line W279 which reacted with anti-FMP1 serum was found to possess three immunoprecipitable surface proteins with molecular weights of 32,000, 50,000, and 70,000. Attempts have been made to identify the antigen(s) expressed by CFU-S and progenitors which were revealed by immunoprecipitation from the tumor lines. The three lower-molecular weight proteins (Mr 28,000-36,000) were chosen for initial study. Membrane extracts of FMP1 cells were fractionated on Sephacryl S-200, and selective pools of these antigens were made. Antisera to these pools exhibited complement dependent cytotoxicity to FMP1 cells, bone marrow CFU-S, granulocyte/macrophage colony-forming cells, and erythroid burst-forming units. These antisera immunoprecipitated Mr 28,000, 32,000, and 36,000 proteins from FMP1 cell membrane extracts but not the Mr 50,000 and 70,000 antigens. The W279 line has only one antigen (Mr 32,000) in the lower-molecular-weight range and is able to absorb anti-CFU-S and anti-progenitor activity, which suggests that it is this antigen which is expressed on hemopoietic cells. In addition, thymocytes react with anti FMP1 serum, and the Mr 32,000 antigen was immunoprecipitated from thymus cell extracts. Binding studies with concanavalin A, wheat germ agglutinin, and lentil lectin indicated that the Mr 28,000-36,000 proteins were glycoproteins. The apparent molecular weights of these proteins on polyacrylamide gels were not altered by reduction and alkylation and therefore do not contain disulfide-linked subunits. PMID- 4027984 TI - Increased gene amplification in L5178Y mouse lymphoma cells with hydroxyurea induced chromosomal aberrations. AB - Chromosomal aberrations and dihydrofolate reductase gene amplification are observed in L5178Y mouse lymphoma cells after treatment with hydroxyurea. The types of aberrations include polyploidy, endoreduplication, chromosome fragmentation, and the presence of extrachromosomal DNA. Hydroxyurea-treated cells analyzed by cell sorting showed a subpopulation of cells with increased DNA and increased dihydrofolate reductase. This subpopulation shows a high incidence of chromosome aberrations and an increased frequency of dihydrofolate reductase gene amplification. Hydroxyurea-treated cells with the normal amount of DNA and dihydrofolate reductase have few aberrations and a low frequency of dihydrofolate reductase gene amplification. We propose that hydroxyurea treatment causes overreplication of DNA and that recombination of overreplicated DNA can lead to chromosome aberrations and gene amplification. PMID- 4027985 TI - Hormone dependency of a serially transplantable human prostatic cancer (HONDA) in nude mice. AB - Human prostatic cancer (HONDA) serially transplanted in nude mice grew well in male mice but not at all in untreated female mice or in castrated male mice. Progressive growth in female mice was obtained by i.m. administration of 1 mg of testosterone twice a week. Estradiol inhibited the growth of the tumor in male mice to some extent; however, some growth was observed. The tumor in untreated male mice retained the histological features of poorly differentiated adenocarcinoma. Tumors in castrated male mice showed reduction in size of tumor cell nests with relative overgrowth of stroma. The tumor in androgenized female mice consisted of columnar epithelial cells with large nuclei and more abundant cytoplasms and a large glandular lumen, showing histology of moderately differentiated adenocarcinoma. High levels of human prostatic acid phosphatase (PAP) were detected in sera from untreated male mice. Testosterone markedly increased the content of serum PAP of androgenized female mice. Estradiol reduced the levels of PAP in sera from untreated male mice regardless of the tumor weight. High-affinity androgen receptors were present in cytosol and in nuclear extract of the tumor in untreated male mice. No measurable amount of progesterone or estrogen receptors was present in cytosol from untreated male mice. PMID- 4027986 TI - Establishment and characterization of four human bladder tumor cell lines and sublines with different degrees of malignancy. AB - We have established four human bladder tumor cultures, designated MGH-U1 to -U4 (also known as EJ, HM, RN, and RB in some previous reports). All have been grown in culture for over 30 passages and were free of Mycoplasma contamination. Characterizations of these cell lines were performed. These include isozyme profile, morphology with light and scanning electron microscopes, karyotype, growth rate, DNA content by flow cytometry, presence of cell surface ABH isoantigens, tumorigenicity in nude mice, lactic acid dehydrogenase isozymes, and colony formation in soft agar. Results obtained from these characterizations confirm that MGH-U1 and -U2 are sublines of a previously established bladder tumor cell line, T-24. These results also show that MGH-U3 and -U4, derived respectively from a grade 1 tumor and an urothelium biopsy with severe atypia, are likely to be independent human bladder cell lines and different from other transitional cell bladder carcinoma cell lines reported. The study further demonstrates that these four cell lines/sublines have different degrees of malignancy and a close correlation, in biological and malignant characteristics, between the cells in culture and those in the original tumors. Therefore these cultures may represent cells at different stages of malignant progression. These can be useful models for studies of the development and progression of bladder tumors and detection and treatment of bladder tumors of different grades and stages. PMID- 4027987 TI - Specific killing of human melanoma cells by 125I-labeled 9.2.27 monoclonal antibody. AB - The anti-melanoma antibody 9.2.27 localizes to melanoma cells when administered i.v. to melanoma patients, but high doses of this antibody alone have no specific cytotoxic effect in vivo. To determine whether radiolabeled antibodies would exhibit specific antimelanoma cytotoxicity in vitro, cell survival curves were established for NCl-N892 human melanoma cells treated with 125I-labeled 9.2.27 monoclonal antibody. The binding capacity per cell was 5 X 10(5) molecules of 9.2.27 immunoglobulin G, and the association constant of binding was 10(10) M-1. Antibody preparations with specific radioactivities of 9-80 microCi/micrograms were used. Colony-forming ability after in vitro exposure to 125I-9.2.27 was determined by a 1-h antibody incubation at saturating concentrations, washing, and cell freezing for various exposure durations. Colony survival was dose dependent, varying with the radioactivity per cell and the exposure time. The survival curves demonstrated no shoulder effect and had a 37% incremental survival dose of 0.5-0.9 X 10(5) decays/cell. Selective killing of melanoma cells was demonstrated in experiments where NCl-N417 lung cancer cells were mixed with the melanoma cells prior to antibody treatment. The NCl-N417 cells did not express the melanoma-associated antigen, were more sensitive to conventional external irradiation than were the melanoma cells, and could easily be distinguished from them by different growth morphology. In spite of a growth advantage for the melanoma cells in the clonogenic assay, the antigen-negative lung cancer cells selectively survived the treatment and were the only surviving cells after 15 days of exposure. PMID- 4027988 TI - Glycosaminoglycan production by murine melanoma variants in vivo and in vitro. AB - Glycosaminoglycan (GAG) synthesis of B-16 melanoma metastatic variants was examined in vivo and in vitro to begin to assess the relationship between the presence of these polymers and the process of primary invasion and metastasis. The variants that were examined for GAG production included the F-1 line that exhibits low metastatic potential, the F-10 line selected for high metastatic potential, and the BL6 line selected for high invasiveness. The F-1 cell line was routinely less invasive than the F-10 and BL6 lines when injected s.c. into the legs of irradiated Swiss Webster mice. All cell lines formed palpable tumors after s.c. injection, but histological sections revealed early and extensive invasion in only F-10 and BL6 tumors. The F-1 tumors were surrounded by a connective tissue capsule and did not begin to invade into host tissue until this structure disappeared approximately 16 days after injection of tumor cells. Some consistent alterations in GAG synthesis, particularly the release of hyaluronic acid and heparan sulfate, were observed among the cell lines in vivo and in vitro, although differences observed in vitro were small and variable. In vivo all tumors were surrounded by a hyaluronic acid-rich zone that was concentrated at the tumor-stromal interface and was transitory. Hyaluronate occurred as a diffuse band around BL6 and F-10 tumors but was confined to a capsule surrounding the less aggressive F-1 tumor. In vitro the BL6 and F-10 cell lines released larger amounts of heparan sulfate and hyaluronic acid than did the F-1 cell line. Differences in release of chondroitin sulfate by the cell lines were not observed. Differences in trypsin-releasable GAG, presumably associated with the glycocalyx, were also not apparent. These results link the release in vitro and organization in vivo of hyaluronic acid and heparan sulfate to invasion and metastasis. PMID- 4027989 TI - Identification of the major serum albumin adduct formed by 4-aminobiphenyl in vivo in rats. AB - Serum albumin was isolated from rats at 27 h after administration of the carcinogen [2,2'-3H]-4-aminobiphenyl. Pronase digestion of the purified albumin yielded a mixture of radiolabeled materials which was resolved into 5 major components by reverse-phase liquid chromatography. From detailed UV, 1H-NMR, and mass spectral analyses, four of these were determined to be 4-aminobiphenyl, 4' hydroxy-4-acetylaminobiphenyl, and two other metabolites, all of which are presumed to be non-covalently associated with the serum albumin. The fifth component, however, resulted from covalent bond formation and was identified as a tetrapeptide containing 3-tryptophanyl-4-acetylaminobiphenyl, the amino acid sequence of which was H2N-ala-trp-ala-val. Since rat serum albumin contains only a single tryptophan residue in a hydrophobic drug binding site, its high selectivity for carcinogen binding suggests a unique role for this protein in the detoxification and/or transport of ultimate carcinogenic metabolites. PMID- 4027990 TI - Lesions of the rete testis in mice exposed prenatally to diethylstilbestrol. AB - Adenocarcinoma of the rete testis is an exceptionally rare and malignant testicular neoplasm. Although treatment of pregnant women with diethylstilbestrol (DES) results in reproductive tract abnormalities in their male offspring, increased incidence of testicular tumors has not been verified. However, recently three cases of seminoma have been described in men prenatally exposed to DES, suggesting an association of prenatal DES treatment and the subsequent development of testicular tumors. This report describes the treatment of outbred pregnant CD-1 mice with DES (100 micrograms/kg) on Days 9 through 16 of gestation and its effects on their male offspring. In addition to nonmalignant abnormalities such as retained testes which have been reported in men exposed prenatally to DES, lesions resembling adenocarcinoma of the rete testis were seen in prenatally DES-treated mice at 10 to 18 mo of age (11 of 233; 5%). No comparable lesions were seen in 96 age-matched control male mice. These results suggest an association of prenatal DES exposure and the subsequent development of testicular lesions in the rete testis of mice. PMID- 4027991 TI - International variations in epidemiology of cancers of the extrahepatic biliary tract. AB - Previous studies of the descriptive epidemiology of biliary tract cancers have not differentiated among different types of biliary tract cancer because until recently the International Classification of Diseases (ICD) did not classify them separately. Recent versions of the ICD now distinguish cancers of the gallbladder, extrahepatic bile ducts, and ampulla of Vater. In order to describe more precisely the distribution of these three cancers, we obtained data from nine cancer registries throughout the world which used the eighth or ninth revision of the ICD. Sex-specific, age-adjusted disease rates were calculated for each disease. Log-linear models were used to evaluate the association of age and sex with the risk of acquiring each disease and to assess whether the risk of acquiring disease or the age and sex distribution of the three diseases varied by geographic location. Gallbladder cancer was the most common of the three diseases and occurred more frequently in females. Extrahepatic bile duct cancer was the next most common disease and occurred equally in both sexes. Cancer of the ampulla of Vater was the least common and was more common in males. The incidence of each of the diseases increased with age. The age and sex distributions of the different diseases different among the nine registries. Thus these three neoplasms differ in their descriptive epidemiology and should therefore be considered separately in clinical practice and in future investigations. PMID- 4027992 TI - Pediatric phase I trial and pharmacokinetic study of tiazofurin (NSC 286193). AB - Tiazofurin (2-beta-D-ribofuranosylthiazole-4-carboxamide), a new nucleoside antimetabolite, was evaluated in a phase I trial involving children with refractory cancers. The drug was administered i.v. as a 10-min infusion daily for 5 consecutive days repeated at 3-week intervals. The dose ranged from 550 to 3300 mg/sq m/day. Seventeen patients received 23 courses and were evaluable for toxicity. The maximally tolerated dose was 2200 mg/sq m/day. The major dose limiting toxicities were nonhematological. Neurotoxicity, including headache, drowsiness, and irritability, was common and was the principal dose-limiting toxicity at the higher doses. Severe myalgias were also dose limiting in one patient. Other side effects were mild, reversible elevations in serum transaminases; nausea, vomiting, and diarrhea; mild hypertension; dysphagia; and exfoliative dermatitis of the hands and feet. Myelotoxicity was not significant. The pharmacokinetics of tiazofurin was studied in 16 patients. Plasma disappearance was triphasic with half-lives of 9.7 min, 1.6 h, and 5.5 h. Clearance was dose related, ranging from 120 ml/min/sq m at 550 mg/sq m/day to 70 ml/min/sq m at 3300 mg/sq m/day. The primary route of elimination was renal with 85% of the drug recoverable in the urine as the parent compound in the 24 h following administration. PMID- 4027993 TI - Prognostic factors in patients with advanced stage prostate cancer. AB - The relationships of 13 potential prognostic factors to objective response to treatment and survival time were investigated, using data gathered on 1,020 patients with advanced stage prostate cancer who have participated in the clinical trials of the National Prostatic Cancer Project. Multivariate statistical analyses revealed that previous hormone response status, analgesics, pain, elevated acid phosphatase, and anemia were the important, independent prognostic factors for objective response to treatment. For survival time, the significant prognostic factors were previous hormone response status, anorexia, elevated acid phosphatase, pain, elevated alkaline phosphatase, obstructive symptoms, tumor grade, performance status, anemia, and age at diagnosis. It is recommended that future treatment protocols for advanced stage prostate cancer take into account heterogeneity of the treatment groups with respect to these factors, either through the design of the protocol, or at the time of analysis. PMID- 4027994 TI - Prognostic relevance of ploidy, proliferation, and resistance-predictive tests in ovarian carcinoma. AB - In a cooperative study specimens of 37 patients with stage III and IV ovarian carcinomas who had been treated with chemotherapy were investigated utilizing flow cytometry and an in vitro short-term test for predicting resistance. Patients with aneuploid tumors had significantly shorter survival rates than did those with diploid tumors. Patients whose tumors showed a low G0/G1 cell proportion or a high proliferation pool (S- and G2/M cell-proportion) seemed to die earlier. There was also a tendency for patients with in vitro resistant tumors to die earlier under chemotherapy than those with sensitive tumors. PMID- 4027995 TI - Modulation of 1-beta-D-arabinofuranosylcytosine metabolism by thymidine in human acute leukemia. AB - Twenty-seven patients with acute leukemia have been treated by sequential 6-day courses of thymidine (30 g/m2 by i.v. continuous infusion, days 1 and 4) and 1 beta-D-arabinofuranosylcytosine (ara-C) (200 mg/m2 by i.v. continuous infusion, days 2,3,5, and 6). Of 25 evaluable patients 4 achieved a complete remission: one of 9 for acute myelogenous leukemia; and 3 of 14 in the blastic crisis of chronic myelocytic leukemia. Six minor responses were also observed. Toxicity was mainly hematological and did not appear to be higher than that expected from ara-C alone. However, thymidine infusions gave rise to headache and somnolence. The clinical benefit of such treatment seems to be limited to the blastic crisis of chronic myelocytic leukemia. Parallel cytokinetic and biochemical studies were performed in order to assess the cytokinetic and metabolic changes induced by both drugs and to correlate them with the clinical response. Recruitment of cells into the S-phase fraction was observed following the first thymidine infusion in the two complete responders and in three of the five nonresponders studied. In contrast to this high pretherapeutic levels of S-phase fraction were observed in most minor responders and in some nonresponders with further decrease following the thymidine infusion. Recruitment of cells into S phase therefore appeared to be an important but not sufficient factor for prediction of complete response to ara-C. Responders in contrast to most nonresponders were characterized by a higher intracellular level of ara-C and its metabolites following the first 24-h infusion of the drug. Deoxythymidine triphosphate and deoxycytidine triphosphate pools were also measured before and during treatment in order to assess if nucleotide pool variations induced by the administration of thymidine can in fact correlate with the intracellular alteration in ara-C metabolism and with clinical response. The level of deoxycytidine triphosphate pools before treatment showed marked interpatient variations but did not correlate with response. As expected, thymidine infusion induced a rise in the deoxythymidine triphosphate pool and a decrease in deoxycytidine triphosphate. The pools, however, generally returned promptly to the pretherapeutic level 24 h after the end of the infusion of thymidine. There were no significant differences between responders and nonresponders in the modulation of these pools. PMID- 4027996 TI - Heterogeneity and prognostic significance of macrophages in human colonic carcinomas. AB - Previously, we reported that high concentrations of eosinophils in human colonic carcinomas are associated with better prognoses, that sections taken 1 cm remote from (deep to) the margin of tumor (SRM) and sections contiguous to the margin (SCM) of tumor and adjacent uninvolved colon contain significantly different concentrations of eosinophils, and that concentrations of eosinophils in SCM and SRM are both useful and complementary for the prediction of prognosis. As a first step towards studying the ecology of the eosinophil in colonic carcinoma and with the goal of identifying other kinds of cells that might be useful for the prediction of prognosis, we counted cells in SCM and SRM that expressed histochemically demonstrable acid phosphatase, alpha-naphthylbutyrate esterase, and peroxidase. The tumors of patients with and without metastases at the time of resection of the primary tumor contained different (P = 0.0314) concentrations of cells with histochemically demonstrable alpha-naphthylbutyrate esterase in SCM but not in SRM. In contiguous 1- to 2-micron sections, morphologically macrophage like cells with histochemically demonstrable acid phosphatase and cells with histochemically demonstrable alpha-naphthylbutyrate esterase were found to be present in different concentrations both in SCM (P less than 0.01) and in SRM (P less than 0.01); i.e., these phenotypic markers appear to identify different subpopulations of macrophages in tumors. In contrast to our previous study of human pulmonary alveolar macrophages, examination of sections stained sequentially for these phenotypic markers that are commonly used for the identification of macrophages in tumors revealed numerous cells in the same sections that expressed histochemically demonstrable acid phosphatase (red) but not alpha-naphthyl butyrate esterase (brown) and vice versa. Several of these markers promise to be useful and complementary for the prediction of prognosis. PMID- 4027997 TI - Effect of intravesical Bacillus Calmette-Guerin on detection of a urothelial differentiation antigen in exfoliated cells of carcinoma in situ of the human urinary bladder. AB - Flow cytometry was used to detect and quantify expression of a urothelial differentiation antigen (Om5) and nuclear DNA in exfoliated epithelial cells of the urinary bladder from 15 patients with nonpapillary carcinoma in situ during and after intravesical therapy with Bacillus Calmette-Guerin (BCG). Before BCG treatment exfoliated cells reacting with the mouse monoclonal antibody Om5 were found in 13 cases. Following treatment Om5 positive cells were still present in 9 cases but 4 patients who had had Om5 positive cells prior to BCG therapy no longer had detectable antigen-positive cells after therapy. Thus intravesical BCG therapy can alter detection of a urothelial differentiation antigen in exfoliated bladder epithelial cells. It is not certain whether this antigen or other differentiation antigens measured by flow cytometry will advance our present techniques for assessing effects of therapy on carcinoma in situ and other bladder tumors. However, five of nine patients showing persistence of Om5 positive cells after therapy were found to have recurrent tumor by biopsy and two others had positive cytology (median follow-up, 13 months). None of the four without detectable antigen-positive cells after therapy had clinical evidence of tumor by cystoscopy, biopsy, or cytology (median follow-up, 12 months). It now appears feasible and desirable to initiate clinical investigations of this and other differentiation antigens in combination with DNA by flow cytometry of bladder irrigation specimens. PMID- 4027998 TI - Correlation of frequency of induced mutation and metastatic potential in tumor cell lines from a single mouse mammary tumor. AB - Spontaneous mutation rates were determined in mouse mammary tumor subpopulation lines that differ in metastatic phenotype. Although there was almost a 9-fold difference in spontaneous rates to ouabain resistance among the three lines tested, the difference did not correlate with ability to metastasize. Similarly a 10-fold difference in spontaneous rates to 6-thioguanine resistance did not correlate with metastatic ability. In contrast, the frequency of ethyl methanesulfonate-induced mutations was associated with metastatic potential. Thus, ethyl methanesulfonate only induced significant numbers of 6-thioguanine resistant colonies in 66 and 410.4 cells, the only 2 of 5 lines tested that spontaneously metastasize at high frequency, and of ouabain resistant colonies in 66, 410.4, and 168 cells, the only lines tested that produce experimental lung metastases after i.v. injection. Differential sensitivity to induced mutation was not correlated with differences in plating efficiency, wild type sensitivity to ethyl methanesulfonate, 6-thioguanine, or ouabain toxicity, ploidy, cell shape, cell size, or ability to engage in metabolic cooperation. PMID- 4027999 TI - Differences in the pharmacokinetics of daunomycin in normal and leukemic rats. AB - We compared the pharmacokinetics of daunomycin (7.5 mg/kg i.v. bolus injection) in normal and leukemic rats using a leukemia model which resembles acute myeloid leukemia in humans. Due to a more rapid decrease in plasma concentration, the area under the plasma concentration/time curve (AUC) for up to 2 h after drug injection was smaller (2.2 times) in the leukemic rats than that for normals. However, due to higher plasma levels during the drug elimination phase, the total AUC0----infinity was somewhat larger (1.3 times) in the leukemic rats. In the leukemia-infiltrated organs (spleen, liver, and lungs), significantly higher daunomycin concentrations (per gram wet weight) were found than in those obtained from normal rats. In contrast, femoral bone marrow from leukemic rats contained less daunomycin (per 10(9) nucleated cells) than did normal marrow. Quantification of the daunomycin uptake in vitro by flow cytometry showed that leukemic cells from bone marrow and spleen have an equal net drug uptake. Our data suggest that, in the presence of a high leukemic cell load, the intravenously injected daunomycin is rapidly taken up and retained by the leukemic tumor mass in, e.g., spleen, liver, and lungs, and that, as a consequence of this, the femoral marrow functions as a kind of pharmacological sanctuary. PMID- 4028000 TI - Combination chemotherapy in vitro exploiting glutamine metabolism of human glioma and medulloblastoma. AB - The human glioma-derived cell line D-54 MG and the human medulloblastoma-derived cell line TE-671 have been shown to be sensitive in culture to the pharmacological interference with glutamine metabolism by acivicin, 6-diazo-5-oxo L-norleucine, and methionine sulfoximine. Using as a guide the multiple contributions of glutamine to the biosynthesis of proteins, purines, and pyrimidines, we now have identified six additional antimetabolites active against these lines in vitro at clinically relevant concentrations. The 50% growth inhibitory levels of the drugs against D-54 MG in 6-day continuous exposure experiments were: L-asparaginase, 0.057 IU/ml; 5-fluorouracil, 0.5 micrograms/ml; 6-mercaptopurine, 0.8 micrograms/ml; actinomycin D, 0.0007 micrograms/ml; N phosphonacetyl-L-aspartic acid, 2.3 micrograms/ml; and 5-azacytidine, 0.2 micrograms/ml (3-day exposure. The corresponding 50% growth-inhibitory values in TE-671 were: L-asparaginase, 0.54 IU/ml; 5-fluorouracil, 1.5 micrograms/ml; 6 mercaptopurine, 4.7 micrograms/ml; actinomycin D, 0.00044 micrograms/ml; N phosphonacetyl-L-aspartic acid, 4.5 micrograms/ml; and 5-azacytidine, 0.49 micrograms/ml. Dipyridamole up to 10 micrograms/ml was inactive against both lines. The isobologram method was used to evaluate the effectiveness of several two-drug combinations which were biochemically designed. The sums of the optimal fractional inhibitory concentrations for the pairs were: acivicin plus L asparaginase, 0.14; acivicin plus methionine sulfoximine, 0.40; 6-diazo-5-oxo-L norleucine plus methionine sulfoximine, 0.60; acivicin plus 6-mercaptopurine, 1.0, all in TE-671; and acivicin plus 5-fluorouracil, 0.79, in D-54 MG. Our findings suggest that an antimetabolite regimen exploiting glutamine sensitivity might improve the chemotherapy of some human gliomas and medulloblastomas. PMID- 4028001 TI - Sex differential and dose dependence of phenobarbital-promoting activity in N bis(2-hydroxypropyl)nitrosamine-initiated thyroid tumorigenesis in rats. AB - Studies were made on the dose and sex dependence of thyroid tumor development in rats pretreated with N-bis(2-hydroxypropyl)nitrosamine (DHPN) followed by exposure to various doses of phenobarbital (PB). A direct dose-response relationship in induction of thyroid tumors was found in both male and female rats. Upon feeding the DHPN-treated rats with basal diet containing 20, 100, 500, and 2500 ppm of PB, the incidences of follicular adenoma were, respectively, 8, 45, 70, and 66% in male rats and 12, 17, 50, and 58% in female rats. Development of papillary adenomas in male rats was observed only at the higher doses of PB, at incidences of 12 and 20% for doses of 500 and 2500 ppm. Follicular carcinoma was also seen at higher doses of PB, at 16 and 12%, respectively, for the 500- and 2500-ppm groups. Neither follicular nor papillary carcinomas were induced in female rats; only a low incidence of papillary adenoma (4%) was observed with a PB concentration as high as 2500 ppm. A single injection of DHPN resulted in production of approximately 1 tumor/female rat and 2.5 tumors/male rat. DHPN combined with posttreatment with PB at doses up to 500 ppm did not increase tumor yield in female rats, whereas a 3-fold increase was observed in male rats for the 500-ppm-treated groups. When PB was increased to 2500 ppm a marked increase (8 fold) in tumor yield in male rats was observed, in contrast to a less than 3-fold increase in similarly treated female rats. PMID- 4028002 TI - Multidrug (pleiotropic) resistance in doxorubicin-selected variants of the human sarcoma cell line MES-SA. AB - The emergence of drug-resistant tumor cells is a major limiting factor in cancer chemotherapy. There is little information about the nature of such resistant variants among human cancer cell populations. Doxorubicin (DOX)-resistant sublines of the human sarcoma cell line MES-SA were selected by continuous in vitro exposure to DOX. Stepwise increases in DOX concentration produced variants which were 25- and 100-fold resistant to DOX. These sublines displayed marked cross-resistance to daunorubicin, dactinomycin, mitoxantrone, colchicine, vincristine, vinblastine, and etoposide and moderate resistance to mitomycin C and melphalan. Cross-resistance was not observed, however, to methotrexate, 5 fluorouracil, bleomycin, carmustine, or cisplatin. DOX resistance in these cell lines appeared to be stable despite long periods of growth in drug-free medium. Two additional marker chromosomes were identified in the 100-fold resistant variant, which indicated clonal selection during drug exposure, but no double minute chromosomes or homogeneously staining regions were noted. Doxorubicin accumulation in the DOX-resistant cells was reduced by approximately 50% compared to that of the sensitive MES-SA cells, as a result of enhanced efflux of DOX from the resistant cells. There was no evidence of appreciable DOX metabolism by either the sensitive or resistant cells. These studies demonstrate marked DOX resistance and multidrug resistance arising in a human sarcoma line during exposure to DOX. The pleiotropic nature of this resistance is similar to that described in other models. Decreased drug accumulation due to enhanced drug efflux is identified as a major mechanism of resistance in these cells, although other factors may also be involved. PMID- 4028003 TI - Effect of amphotericin B on Adriamycin transport in P388 cells. AB - In Adriamycin-sensitive and -resistant P388 cells, coincubation with amphotericin B causes a marked increase in Adriamycin retention, as determined by laser flow cytometry. P388/S cells were generally more affected than were P388/R cells. Preincubation with amphotericin B had a greater effect on Adriamycin retention than did co- or postincubation. In splenocytes, bone marrow, and ascites from mice, enhanced Adriamycin retention was seen in all the tissues. However, bone marrow cells showed heterogeneous response, with some populations being more sensitive than others. PMID- 4028004 TI - Long-term persistence of ethyl carbamate-induced sister chromatid exchanges in murine lymphocytes. AB - Ethyl carbamate-induced sister chromatid exchange (SCE) was evaluated at 20 min and 1, 3, 4.5, 5.5, 7, and 9 h postexposure (acute dose, ethyl carbamate, 3.3 mmol/kg) in concanavalin A (Con A)- and lipopolysaccharide (LPS)-stimulated murine peripheral blood lymphocytes (PBL). In both Con A- and LPS-stimulated PBL, SCE responses peaked between 4.5 and 5.5 h postinjection, a time which corresponds to complete biotransformation of ethyl carbamate. Peak induced SCEs for Con A- and LPS-stimulated PBL were 6.43 and 7.44, respectively. SCE responses were also evaluated in Con A- and LPS-stimulated PBL at 3 and 24 h following the last of a series of two, four, or six i.p. injections of ethyl carbamate (3.3 mmol/kg) given every other day. Dose-related increases (presumably reflecting the accumulation of unrepaired SCE-inducing damage) in SCEs were observed at both times following two and four injections of ethyl carbamate. However, following six injections a decrease in SCE response and increased cytotoxicity were observed. Persistence of SCE-inducing DNA lesions was observed in blood, spleen, and parathymic node lymphocytes following the last of a series of 12 i.p. injections (three times weekly) of ethyl carbamate (2.2 mmol/kg). With the exception of LPS-stimulated blood lymphocytes, exposed blood and spleen Con A- and LPS-stimulated lymphocyte populations contained a significantly higher number of high-frequency cells than did their respective controls at 16 weeks postexposure. The gradual return of SCE levels to base-line values appears to be primarily a consequence of slow population turnover. Parathymic node lymphocytes exhibited elevated SCE responses (2 times base-line levels) for up to 4 weeks postexposure. PMID- 4028005 TI - Cell killing and sensitization to heat shock by hypothermic incubation of asynchronous and synchronized mouse neuroblastoma cells. AB - The effect of hypothermia on cell survival and on subsequent response to hyperthermia was studied in asynchronous and synchronized Neuro-2A cells. Cell cycle progression was blocked at temperatures below 27 degrees C. Immediately after shift to hypothermic temperatures, cells became more sensitive to hyperthermia. Development of thermosensitization was time and temperature dependent. Thermosensitization of cells by hypothermia was high at 0 degrees C and 15 degrees-30 degrees C and less at 5 degrees-10 degrees C. Sensitization started to occur before hypothermic cell death became manifest and developed gradually. Hypothermic cell death was observed when the cells were incubated for more than 1 day at temperatures of 0 degrees-24 degrees C with a minimal cell death during incubation at 6 degrees C. Thermosensitization of cells by hypothermia depended on the position of the cell in the cell cycle at the time of shift to hypothermic temperatures. Cells in late G1 and early S phase became more thermosensitive than did cells in G1 or late S-G2 phase. Furthermore G1-S cells were more sensitive to prolonged hypothermia alone than were G1 or late S-G2 cells. In contrast, late S-G2 cells were most sensitive to hyperthermia alone. It is concluded that the temperature- and cell cycle-dependent way of hypothermic induced cell death was similar to the thermosensitization of cells by hypothermia. But thermosensitization became manifest prior to the actual cell death, following hypothermic treatment. PMID- 4028006 TI - Mechanistic implications of the induction of thermotolerance in Chinese hamster cells by organic solvents. AB - Several organic solvents were shown to induce thermotolerance. These included: aliphatic alcohols (ethanol to octanol); local anesthetics; dimethyl sulfoxide; and dimethyl formamide. The minimum concentrations of the various alcohols required to induce tolerance were similar to the threshold doses for cytotoxicity. When only intramembrane concentrations were considered (by multiplying by the appropriate membrane:buffer partition coefficient), then the alcohols' threshold dose to induce tolerance was only mildly a function of carbon number. The efficiency increased almost linearly with a membrane dose from propanol to pentanol, but was slightly reduced for octanol. All alcohols induced tolerance rapidly (within a few hours after 30-min exposure), but the thermotolerance ratio decreased with increasing carbon number. Of the three anesthetics examined, lidocaine was a highly efficient inducer, procaine less so, and tetracaine did not induce tolerance even at a concentration mildly cytotoxic. Dimethyl sulfoxide and dimethyl formamide induced tolerance without cytotoxicity, but the kinetics of doing so was different from that seen with the other solvents. Only cells exposed to these water-soluble agents for 18 h or longer showed evidence of induced heat resistance. Our results indicate that membranes likely are the site for the initiation of solvent-induced cell killing and thermotolerance. The minimum dose of induction may be related to the degree of disorder induced by the individual alcohol, but the amount of tolerance induced is inversely related to this. The data on the effects of local anesthetics show that neither their common functional mode of inhibiting nerve transmission nor their similar level of cytotoxicity insures similar efficiency as tolerance inducers. Results with dimethyl sulfoxide and dimethyl formamide suggest that tolerance can be induced by more than one mechanism, or alternately, that a multiple-step mechanism can be activated at different points along this pathway. We also measured heat shock protein synthesis after several treatments; efficient inducers of thermotolerance also induced these proteins. PMID- 4028008 TI - Effect of thermochemotherapy (combined cyclophosphamide and hyperthermia) given at various temperatures with or without glucose administration on a murine fibrosarcoma. AB - The effect of combined cyclophosphamide (CY) and heat treatments on a murine tumor was studied at various temperatures. FSa-II tumors, the early generation isotransplants of a spontaneous fibrosarcoma in a C3Hf/Sed mouse, were used. A single cell suspension was transplanted into the animal foot. Hyperthermia was given by immersing animal feet into a water bath maintained at a desired temperature +/- 0.1 degrees C. An average diameter of the tumor at the time of treatment was 4 mm. The tumor growth time, the time required for one-half of the treated tumors to reach 1000 mm3, was the end point. Hyperthermia enhanced the effect of CY at test temperatures ranging from 40.5 degrees - 44.5 degrees C. The enhancement was independent of the temperature when CY was administered 30 min before the beginning of hyperthermia. However, the enhancement was most substantial at temperatures of 40.5 degrees -42.5 degrees C when CY was administered immediately before hyperthermia. The most effective timing of the CY administration was immediately before hyperthermia. The glucose administered 60 min before hyperthermia enhanced the effect of combined CY and hyperthermia when CY was given 30 min before heating. This enhancement was lost when CY was given immediately before hyperthermia. The CY dose response curves at elevated temperatures were downward concave, which may indicate the presence of a CY- and heat-resistant cell population in the tumor. Implications of these observations in clinical hyperthermia were discussed. PMID- 4028007 TI - Radiolocalization of xenografted human malignant melanoma by a monoclonal antibody (9.2.27) to a melanoma-associated antigen in nude mice. AB - A murine monoclonal antibody (9.2.27), directed to a Mr 250,000 glycoprotein chondroitan sulfate proteoglycan complex, was radiolabeled with 125I and assessed for radiolocalization in tumor and normal tissues of normal and tumor-bearing nude mice. The 125I-9.2.27 localized in vivo preferentially in Mr 250,000 antigen expressing human melanomas (FMX-Met, SESX) but not in low antigen-expressing tumors (LOX-L) xenografted in nude mice. The imaging index of tumor cells was positively correlated with the antigen density of the various melanoma cell lines as measured by flow cytometry. The nonspecific immunoglobulin RPC-5 of the same IgG2a subclass as 9.2.27 did not specifically localize to xenografts of melanoma. The total amount of 125I-9.2.27 accumulated in the tumor was directly correlated with tumor size. However, the specific radioactivity (cpm/g) in smaller tumors was higher than that in larger tumors. Nonspecific uptake and circulating antibody levels differed between normals and tumor-bearers. The organs of the reticuloendothelial system of normal mice accumulated more labeled antibody than did those of tumor bearers, and conversely, tumor bearers had higher levels of circulating labeled antibody in the blood than normals. The circulating labeled antibody in tumor bearers was still monomeric but had no detectable antigen binding capacity. PMID- 4028009 TI - Effect of melatonin on B16 melanoma growth in athymic mice. AB - The effect of melatonin on the growth of B16 mice melanoma was examined. Male and female BALB/c athymic mice, inoculated with 7 X 10(4) melanoma cells, were given drinking water containing melatonin (5 micrograms/g body weight/day) and 0.5% ethanol. Compared to control animals the melatonin treated male and female athymic mice had significantly smaller tumors on Day 40. The weights of the testes, the ovaries, and the adrenal glands of melatonin treated mice were significantly reduced compared to control animals. These data indicate that melatonin p.o. significantly inhibited the growth of B16 mouse melanoma and that the antitumor effect of melatonin was associated with a significant decrease in gonadal and adrenal weights. PMID- 4028010 TI - Factors affecting growth and drug sensitivity of mouse mammary tumor lines in collagen gel cultures. AB - A series of mouse mammary tumor subpopulation lines were compared for growth properties and sensitivity to chemotherapeutic drugs when grown as boluses in a collagen gel matrix versus in monolayer culture. Although the cell lines exhibited characteristic rates of bolus expansion in collagen, this growth was not paralleled by an exponential increase in cell number with time. Cell boluses contained a higher proportion of cells in G0-G1 phases of the cell cycle than did the same cell lines in monolayer cultures. Histological examination revealed areas of necrosis in boluses. Thus cells growing in collagen cultures resembled cells growing as solid tumors and cells from other three-dimensional culture systems. The growth of cell boluses in collagen gel cultures was reduced nonexponentially by melphalan, methotrexate, and 5-fluorouracil in contrast to the exponential decrease in growth measured in cloning assays. The lowest concentration to which cells first responded to drug was in general similar for collagen gel assays and for cloning assays. The rank order of sensitivity of different cell lines in the two assays was identical for methotrexate (four cell lines), similar for melphalan (four of five lines), but quite different for 5 fluorouracil. In contrast to cloning assays cell boluses continued to grow, albeit at a reduced rate, in the presence of high drug concentrations. This was not due to either diminished drug availability in collagen gel or drug penetration into the bolus. PMID- 4028011 TI - Synergistic effects of combination sequential immunotherapies in a murine ovarian cancer model. AB - The antitumor effects of Corynebacterium parvum in a murine ovarian teratocarcinoma model depend upon a sequential activation of neutrophils and macrophages within the peritoneal cavity. We studied the sequential administration of biological response modifiers that independently activate each phase of the response. Tumor-challenged mice treated by i.p. injection of a pyridine-extracted fraction of cell-free Propionibacterium acnes (PA-PE, 1400 micrograms) demonstrated prolonged survival in less than 20% of the cases. An i.p. injection of a detoxified Salmonella endotoxin (DSE) preparation (150 micrograms) had no effect on tumor outgrowth. However, i.p. treatment with PA-PE (1400 micrograms), followed by 150 micrograms of DSE 1 day later, resulted in long-term survival (greater than 100 days) in 40 to 60% of mice. This antitumor effect was only evident when PA-PE was administered first (before DSE) and optimal when DSE was administered 24 h after PA-PE. The synergistic antitumor effect could be duplicated when tumor-challenged mice were first treated i.p. with peritoneal polymorphonuclear leukocytes, elicited by injection of PA-PE, and then treated with DSE 18 h later. These data indicate that appropriately timed injection of biological response modifiers with complementary effects can result in a synergistic prevention of tumor growth. PMID- 4028012 TI - Binding of metabolites of cyclophosphamide to DNA in a rat liver microsomal system and in vivo in mice. AB - The stability of phosphoramide mustard, a metabolite of cyclophosphamide was studied at pH 7.2 and 37 degrees C using 31P nuclear magnetic resonance. The phosphorus signal of phosphoramide mustard disappeared with a half-life of 8 min indicating rapid conversion to other species. The final product, inorganic phosphate, appeared with a half-life of 105 min indicating that phosphoramide mustard was easily dephosphoramidated. A rat liver microsomal system was used to study the binding of [chloroethyl-3H]cyclophosphamide to DNA. DNA was hydrolyzed in 0.1 N HCl:0.5 N NaCl at 80 degrees C for 20 min, conditions known to convert phosphoramide mustard to nornitrogen mustard with liberation of the phosphoramide residue. After such treatment three adducts were detected by high-performance liquid chromatography using several elution systems. They were all 7-substituted guanine adducts of nornitrogen mustard; two were monoalkylation products with an intact [N-(2-chloroethyl)-N-[2-(7-guaninyl)ethyl]amine] or an hydroxylated mustard arm [N-(2-hydroxyethyl)-N-[2-(7-guaninyl)ethyl]amine]; the third adduct was a cross-linked product [N,N-bis [2-(7-guaninyl)ethyl]-amine]. The relative abundance of these adducts depended on the length of the microsomal incubation. After 2 h, N-(2-chloroethyl)-N-[2-(guaninyl)ethyl]amine was the main product but after 6 h N-(2-hydroxyethyl)-N-[2-(7-guaninyl)ethyl]amine was most abundant, and at this time the cross-linked product represented 12% of the total adducts. The adducts in DNA depurinated readily and after 24 h at pH 7.0 and 37 degrees C 70% of them had been liberated. The rate of depurination was decreased in the presence of 0.5 N NaCl. After short-term depurination in 0.1 N HCl at 25 degrees C the primary alkylating species was phosphoramide mustard rather than nornitrogen mustard. In in vivo studies mice were given injections i.p. of 100 microCi of cyclophosphamide. Maximal levels of radioactivity had been incorporated into DNA between 2-7 h after injection; the specific activity of DNA from the kidney and lung exceeded that from the liver. While the level of radioactivity found in kidney DNA was rapidly reduced the rate of fall was lower in the lung. Between 24 and 72 h the specific activity of lung DNA exceeded that of kidney and liver DNA by a factor of 3:8. Lung is the principal target tissue for tumor formation in mice after an i.p. injection. PMID- 4028013 TI - Effects of mutagens on the immunogenicity of murine tumor cells: immunological and biochemical evidence for altered cell surface antigens. AB - Eb lymphoma cells were subjected to treatment in vitro with the alkylating mutagen N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) and then cloned by limiting dilution. When tested in vivo for tumorigenicity in groups of syngeneic DBA/2 mice, 6 from 18 clones were found to be strongly reduced (tum- phenotype). The other clones showed only moderate or no change in tumorigenicity compared to the untreated control. All clones were able to grow in 400-rad-irradiated mice. Mice in which MNNG clones had regressed were able to generate tumor-specific cytolytic T-lymphocytes in vitro. Limiting dilution analysis indicated that 3 of 4 MNNG clones analyzed in detail displayed additional antigenic determinants that were detected by cytolytic T-lymphocytes. These data thus provided evidence for increased immunogenicity of some of the MNNG clones. Membrane proteins of MNNG clones and original Eb cells were compared biochemically after metabolic labeling with [35S]methionine, TX114 solubilization, and electrophoretic separation. Two dimensional gel maps revealed a general quantitative decrease in the expression of membrane proteins in MNNG clones. In addition, several proteins were only found in MNNG clones but not in untreated cells. Two membrane proteins of molecular weight 22,000 and 38,000 were greatly increased in expression in all MNNG clones but could be detected at a low level in the original Eb cells. MNNG is known to be a strong mutagenic agent, but it can also interfere with DNA methylation and cause transcriptional activation of genes. We suggest that amplified cell surface structures may be the consequence of such transcriptional activation and could be involved in altered immunogenicity. PMID- 4028014 TI - Autoradiographic demonstration of estrogen binding in human breast cancer after in vitro incubation. AB - This report describes the localization of bound radioactivity as visualized by thaw-mount autoradiography in 35 cases of human breast carcinoma after in vitro incubation with [3H]estradiol. The findings have been compared qualitatively with results of biochemical assays. Twenty-six tumors were considered to be estrogen receptor positive by autoradiographic criteria. Of these, 23 were assayed biochemically; 21 were found to be positive. Specific uptake of radioactivity was observed primarily in neoplastic epithelial cells. The grains were localized mainly over the nuclear region of putative target cells. Within nests of infiltrating carcinoma, positive cells could be identified admixed with negative cells. There were no autoradiographic criteria established for borderline cases. The remaining nine cases were considered negative. In these cases the appearance of tissue exposed only to [3H]estradiol resembled that of tissue incubated with excess unlabeled estradiol. The few grains were randomly scattered with no evidence of nuclear localization. Of these negative cases, two were positive by biochemical assay, four borderline, and three negative. It is concluded that, as assessed in this investigation, estrogen receptor-positive mammary carcinomas may be composed of target and nontarget neoplastic cells. Thaw-mount autoradiography should prove useful in the laboratory investigation of steroid hormone responsiveness of human breast carcinoma. PMID- 4028015 TI - Biology of cell killing by 1-beta-D-arabinofuranosylcytosine and its relevance to molecular mechanisms of cytotoxicity. AB - Cells of the Chinese hamster ovary cell line were used to study the process of cell death induced by pulse treatment with 1-beta-D-arabinofuranosylcytosine (ara C). Cells were synchronized by mitotic selection and pulse treated in early S phase with a concentration of ara-C (1 mM) which was sufficient to reduce plating efficiency to a few percentages of the control. The process of when and how the lethally damaged cells die was studied using a series of techniques in parallel. These included time-lapse microcinematography, flow microfluorimetry, and chromosome morphology in both anaphases/telophases and Colcemid-arrested metaphases. Most of the lethally damaged Chinese hamster ovary cells progressed through one, and many through two, cell cycles before death occurred. The cell death and abnormal divisions can be accounted for by the chromosome aberrations observed in Colcemid metaphases and anaphases/telophases. Death without any attempted division occurred between 3 and 9 normal cell cycle times after ara-C treatment. Chinese hamster ovary cells were also treated continuously with 1 mM ara-C. Under these conditions, cell death was still primarily division related. We argue that these data are not consistent with the actual incorporation of ara C moieties into DNA being the primary cause of cell death. The data are discussed in relation to the postulated molecular mechanisms of toxicity of this drug. PMID- 4028016 TI - Comparison of the morphology and enzyme activity of mononuclear cells from Fischer 344 rats with either spontaneous or transplanted leukemia. AB - Mononuclear cell (MNC) leukemia was identified in 26-month-old F344 rats by splenomegaly, reduced red blood cell counts, and elevated white blood cell counts. Atypical MNC were predominant in spleen and blood with acentric nuclei and red cytoplasmic granules. Pentose shunt, glycolytic, and Krebs cycle enzyme activities were elevated 2- to 11-fold in the enriched MNC fraction (Ficoll-Paque density gradients, 1.077 g/ml) isolated from spleen. A leukemic MNC line was derived from one of the spontaneously leukemic donors and then maintained in vivo by s.c. transfer of 2 X 10(7) spleen cells into 7-8-week-old syngeneic recipients. In these serial transplantation experiments leukemia that was clinically and morphologically indistinguishable from spontaneous leukemia in 104 week-old rats was induced in 22-24-week-old rats. Enhanced enzyme activity in MNC was not essential to maintain the phenotypic expression of Fischer rat leukemia. The pattern of biochemical response in spleen MNC from transplanted cases was the opposite of that previously noted in spontaneously leukemic rats, with 50-70% decreases in the specific activities of pentose shunt enzymes and malate dehydrogenase. Reversal of the expression of these enzymes in MNC may be related to a difference in the growth rate of the tumors or to selective proliferation of the transplanted leukemic cells. In addition acetylcholinesterase activity decreased 35-85% in MNC of spleen and blood. Transplantable MNC from F344 rats provide abundant tumorigenic material with a novel biochemical expression that may be useful in the study of chemotherapeutic intervention. PMID- 4028017 TI - Relationship of queuine-lacking transfer RNA to the grade of malignancy in human leukemias and lymphomas. PMID- 4028018 TI - Peritoneal mesothelial cell injury factors in rat cancerous ascites. AB - To elucidate the mechanism of the peritoneal dissemination of cancer, the influence of cancerous ascites on peritoneal mesothelial cells was studied by scanning electron microscopy and light microscopy. We inoculated normal Donryu rats with AH100B ascites hepatoma cells and studied the influence of the supernatant from cancerous ascites on the normal rat peritoneal surface by i.p. injection. The mesothelial cells were damaged and exfoliated markedly, which is supposed to be a profitable condition for cancer cells to proliferate on the peritoneal surface. Therefore, the presence of mesothelial cell injury factors was noted. Subsequently, we divided the supernatant from rat cancerous ascites into four fractions by gel filtration and revealed the distribution of mesothelial cell injury factors by studying the influence of each fraction on the normal rat peritoneal surface. Although Fraction I (fibrin fraction) and Fraction II (IgG fraction) made no changes on the peritoneal surface, Fraction III (albumin fraction) and Fraction IV provoked damages on the mesothelial cells. We found that the mesothelial cell injury factors are present in the albumin fraction and in the fraction containing low-molecular-weight substances. PMID- 4028019 TI - Inhibition of tumor cell colony formation in culture by a monoclonal antibody to endogenous lectins. AB - The presence of endogenous, galactoside-specific lectin molecules on the surface of various neoplastic cells has been demonstrated recently using monoclonal antibody (mAb) 5D7 [Raz et al., EMBO (Eur. Mol. Biol. Organ.) J., 3: 2979, 1984]. The effect of this mAb on the growth of several transformed and tumor cell lines of murine and human origin was investigated using in vitro techniques. A dose dependent reduction (30 to 100%) in colony formation on a solid substrate or in a semisolid medium was observed when the cells were cultured in the presence of 15 to 100 micrograms of mAb 5D7 per ml of medium. Inhibition of anchorage independent growth was more pronounced (2- to 3-fold) than inhibition of anchorage-dependent growth for most of the cells. The growth-inhibitory effects of mAb 5D7 were not the result of a cytolytic activity, for neither DNA nor protein synthesis was suppressed in semiconfluent cell cultures after 3 days of exposure to the antibody. Other mAbs that recognize cell surface components, such as chondroitin sulfate or fibronectin, failed to inhibit colony formation. These results suggest that endogenous tumor cell-surface lectin molecules may be involved in intercellular interactions or interactions between the cells and exogenous ligands; these interactions are important for growth regulation. PMID- 4028020 TI - Cellular heterogeneity in normal and neoplastic human urothelium. AB - Cell suspensions derived from 2 specimens of normal human urothelium and 13 human transitional cell carcinomas were studied by discontinuous density gradient centrifugation. The histochemical and proliferative properties of the fractions were evaluated. In normal urothelium, DNA synthesis was restricted to a subpopulation of small round cells which could be partly separated from the more numerous pyramidal and giant cells on the basis of their higher physical density. Normal urothelium did not form colonies in agar. In well-differentiated tumors, the majority of cells present were low-density, elongated cells which histochemically resembled the differentiated pyramidal cells of normal tissue, but DNA synthesis and the ability to form colonies in agar were restricted to a subpopulation of high-density small round cells. Colony size analysis showed that intermediate-density bands contain cells capable of a few divisions which do not form large colonies. With increasing tumor grade, there was an apparent shift into the high-density clonogenic compartment. PMID- 4028021 TI - Increased level of amplification of the c-myc oncogene in tumors induced in nude mice by a human breast carcinoma cell line. AB - Cell line SW 613-S, derived from a human breast carcinoma, contained double minute chromosomes (DMs) but lost them progressively upon in vitro cultivation. These cells were tumorigenic in nude mice. Cell lines were derived from the tumors and were found to have a high DM content. In three such cell lines, DMs were stably maintained upon in vitro cultivation, whereas in another they were progressively lost. We found that the c-myc oncogene is amplified 5- to 10-fold in SW 613-S and 20- to 90-fold in the different cell lines derived from the tumors. At least part of the additional c-myc copies were found associated with a purified DM fraction. In cell lines which lost the DMs during in vitro passages, the level of amplification was maintained. In situ hybridization experiments indicated that this loss was compensated by the acquisition of copies of the c myc gene integrated into a chromosome. No major rearrangement of the amplified c myc gene was detected. The amount of c-myc messenger RNAs is roughly proportional to the level of amplification. Our results indicate that growth of SW 613-S cells as tumors in nude mice selected cells with an increased level of amplification and expression of the c-myc oncogene. PMID- 4028022 TI - Ability of specific monoclonal antibodies and conventional antisera conjugated to hematoporphyrin to label and kill selected cell lines subsequent to light activation. AB - A variety of cell lines have been prepared by fusion of the murine WEH1 3B cell line with peripheral blood leukocytes from a patient with chronic granulocytic leukemia. Fusion products were selected for their ability to produce a leukemia associated antigen (CAMAL) previously described. One such line which originally produced CAMAL subsequently lost this ability and was used as a negative control. A number of antibodies were conjugated to hematoporphyrin (HP) and tested for their ability to bind to cell lines as detected by either fluorescence or by their ability to kill cells after light activation. The antibodies used were: rabbit anti-Hu (a conventional rabbit antiserum raised to membrane preparations from normal human peripheral blood leukocytes which served as a positive control); CAMAL-1 (a monoclonal gamma 1 antibody with specificity for the CAMAL antigen); and L1210 (an irrelevant monoclonal gamma 1 antibody). HP was conjugated to the antibodies by a carbodiimide procedure. When labeled cells were examined by fluorescence microscopy, it was apparent that both the rabbit antibody and CAMAL-1:HP showed positive labeling. The ability of the antibody:HP conjugates to kill labeled cells following light activation was tested. It was shown that rabbit anti-Hu:HP and CAMAL-1:HP conjugates were capable of killing significant numbers of cells when HP concentrations were as low as 1.2 ng/10(6) cells, whereas similarly treated cells exposed to either L1210:HP or HP alone did not exhibit significant killing until concentrations reached 240 and 120 ng/10(6) cells, respectively. Further experiments in which other cell lines were tested, all at HP concentrations of 12 ng/10(6) cells, demonstrated that those lines producing CAMAL were killed, whereas negative lines were not. PMID- 4028023 TI - Comparison of binding proteins on the surface of murine tumor cells for two lectins active in the lectin-dependent macrophage-mediated cytotoxic reaction. AB - The binding proteins for Sarcophaga lectin and wheat germ agglutinin on the surface of Ehrlich ascites tumor cells were compared. Studies with antibody against the binding protein for Sarcophaga lectin showed that these two binding proteins are different. Since these two lectins are both active in the lectin dependent macrophage-mediated cytotoxic reaction with Ehrlich ascites tumor cells as target cells, there must be multiple proteins on the surface of target cells that can trigger cytolytic reaction in response to different lectins in the presence of macrophages. PMID- 4028024 TI - Surface antigens of melanomas and melanocytes defined by mouse monoclonal antibodies: specificity analysis and comparison of antigen expression in cultured cells and tissues. AB - Mouse monoclonal antibodies (mAb) detecting 13 distinct systems of surface antigens on cultured melanocytes and melanomas were tested for reactivity with panels of (a) normal and malignant cultured cells; (b) normal adult and fetal tissues; and (c) specimens of metastatic melanoma and other tumor types. The objectives of this study were to compare antigen expression in cultured versus noncultured cells, to develop a panel of mAbs that identify subsets of melanomas, and to provide requisite information about antibody specificity in preparation for the use of antibodies in the diagnosis, imaging, and therapy of melanoma. Five of the melanoma surface antigens have been well characterized biochemically [GD3, chondroitin sulfate proteoglycan, HLA Class II antigens, glycoprotein of molecular weight 130,000 (gp130), and glycoprotein Mr 95,000/protein Mr 97,000 (gp95/p97)]. Three antigens have been related to melanocyte differentiation (HLA Class II, M111/M231, and M144), and six provide additional markers for subsets of cultured melanomas. mAb R24 reacts with the disialoganglioside GD3, a predominant ganglioside on cultured melanoma cells and other cells of neuroectodermal origin. A high proportion of melanoma, astrocytoma, and sarcoma tissue specimens were GD3+. In normal tissues, reactivity of mAb R24 was restricted to melanocytes, neuronal and glial cells in the central nervous system, parotid gland, adrenal medullary cells, and rare cells in the connective tissue. mAb B5 detects a chondroitin sulfate proteoglycan that is expressed by most melanoma and astrocytoma cell lines and by cultured melanocytes. Most of the melanoma and astrocytoma specimens were B5+, whereas other tumor types tested were B5-. mAb 13 17, which detects a monomorphic determinant of HLA Class II antigens, reacted with melanomas, and with a variety of other cancers, but not with normal skin melanocytes. There is considerable variability in the expression of GD3 and HLA Class II antigens in individual melanoma specimens; cotyping for these two antigens showed no evidence for coordinate expression. mAb L101 detects gp130 and mAb L235 detects gp95, antigens that are strongly expressed on a broad range of cultured cell types. In contrast to their wide distribution on cultured cells, gp130 expression in tissues was generally restricted to a subset of melanomas and some normal cells, and gp95 was detected on only a small number of melanomas. mAb M111/mAb M231 and mAb M144 define intermediate and late stage differentiation markers of cultured melanocytes and melanomas.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 4028025 TI - Increased carbamoyl-phosphate synthetase II concentration in rat hepatomas: immunological evidence. AB - Carbamoyl-phosphate synthetase II (glutamine hydrolyzing, EC 6.3.5.5) (synthetase II), the rate-limiting enzyme of de novo uridine monophosphate biosynthesis, was purified 230-fold to apparent homogeneity from rapidly growing rat hepatoma 3924A. The antiserum (produced in rabbits against purified hepatoma 3924A enzyme) yielded a single precipitin line with crude and partially purified synthetase II of normal liver and three hepatomas. In hepatomas of slow (20), intermediate (7787), and rapid (3924A) growth rates, synthetase II activity was elevated 1.5-, 2.3-, and 7.9-fold, and the amount of antiserum required to inactivate the activity was 1.6-, 2.3-, and 8.2-fold higher than that in normal liver. Thus the increase in synthetase II activity in the tumors was due to an elevation in the amount of the synthetase II enzyme protein. PMID- 4028026 TI - Amplification and elevated expression of c-myc in a chemically induced mouse colon tumor. AB - The amplification and level of expression of four cellular oncogenes was investigated in dimethylhydrazine-induced Mouse Colon Tumor 36 of Corbett et al. [Corbett, T. H. Griswold, D. P., Jr., Roberts, B. J., Peckham, J. C., and Schabel, F. M., Jr. Cancer (Phila.), 40:2660-2680, 1977], which has been used to evaluate potential chemotherapeutic agents. A 30- to 40-fold amplification of c myc was observed in the tumor DNA as compared to the DNA of normal colonic mucosa and liver. No changes were observed in the number of copies of c-mos, erbB, or bas. Digestion with three different restriction enzymes demonstrated that there was no major alteration in the genomic structure of c-myc in the amplified DNA. The level of c-myc RNA was 10-fold higher in both the total and polyadenylated RNA from the tumor when compared to RNA from normal colonic mucosa. Probes specific for the three myc exons were used in hybridization experiments and demonstrated that all three exons were present in the amplified DNA and in the mRNA. PMID- 4028028 TI - Stability of c-K-ras amplification during progression in a patient with adenocarcinoma of the ovary. AB - We have identified a case of serous cystadenocarcinoma of the ovary in which the tumor cells display an amplification (from 10- to 20-fold) of the cellular oncogene K-ras. Normal cells purified from the malignant ascites did not show such amplification. Five consecutive samples were obtained by paracentesis over a 9-month period during which the patient received chemotherapy and underwent clinical progression. The level of c-K-ras amplification in the tumor cells did not change during this period. In studies of the tumors of 6 additional patients with adenocarcinoma of the ovary and 5 cell lines of the same histology, we have detected no other example of significant c-K-ras amplification. PMID- 4028027 TI - Intraperitoneal recombinant alpha-interferon for "salvage" immunotherapy in stage III epithelial ovarian cancer: a Gynecologic Oncology Group Study. AB - Fourteen patients with persistent epithelial ovarian cancer documented at second look laparotomy after combination chemotherapy were treated with 146 cycles of alpha-recombinant interferon (rIFN-alpha 2) administered i.p. The initial dose was 5 X 10(6) units which was escalated weekly to 50 X 10(6) units over 4 weeks and then continued weekly for a total of 16 weeks. Eleven patients underwent surgical reevaluation after therapy which confirmed four pathological complete responses (36%), one partial response (9%), and disease progression in six patients (55%). Five of seven patients (71%) with residual tumor less than 5 mm had a surgically documented response, whereas there was no response in the four patients whose tumors were greater than or equal to 5 mm. Three patients were evaluable for clinical response only: one patient who refused surgery had a complete clinical response with total resolution of ascites; one had stable disease; and one had disease progression. Fever greater than or equal to 38 degrees C was seen in 58%, fever greater than or equal to 39.0 degrees C was seen in 18%, vomiting in 37%, abdominal pain was reported in 22%, and one patient had infectious peritonitis. Peripheral white blood cell counts and i.p. washings were obtained pretreatment and on days 1, 3, and 7 after treatment. While there was no consistent alteration in peripheral white blood cell counts, the numbers of i.p. monocytes and lymphocytes showed a significant boost on day 1 after each dose of rIFN-alpha 2. Natural killer lymphocyte cytotoxicity was elevated in the i.p. cavity fluid obtained from most patients on day 1 after treatment, while blood natural killer lymphocyte cytotoxicity values showed considerable variability. Pharmacokinetic studies show that i.p. levels of rIFN-alpha 2 were 30-1000 times blood levels. rIFN-alpha 2 i.p. may act by increasing concentrations of drug and augmenting regional host cells in patients with minimal residual ovarian cancer. PMID- 4028029 TI - Humoral immune response of patients receiving specific active immunotherapy for renal cell carcinoma. AB - The object of this study was to characterize the antigens evoking an immune response in renal cell carcinoma (RCC) patients receiving specific active immunotherapy with irradiated autologous tumor cells and Corynebacterium parvum as adjuvant. Seventy serum samples from 11 patients with RCC undergoing specific active immunotherapy were evaluated. Fifty of the 70 serum specimens (71%) had immunoglobulin G antibody directed to autologous tumor cells. Absorption studies were completed on 4 patients (S.E., M.M., R.N., S.V.) with 2 patients (S.V. and M.M.) demonstrating reactivity to a RCC-associated antigen present on their autologous tumor cells. One patient's serum (R.N.) was absorbed not only with autologous tumor cells but also with an allogeneic RCC cell line. The fourth patient's (S. E.) serum reactivity was able to be absorbed only with autologous tumor cells and several, but not all, of the clones of that autologous cell line. Patient S.E. serum binding by clones of RCC cell line RPMI-SE was seen to vary from no ability to bind RPMI-SE in some clones to double the parental binding in others. Consistent with this finding was the demonstration that high serum binding clones could absorb Patient S.E. serum reactivity to autologous RCC cells, while low binding clones could not. These data suggest a measure of heterogeneity among the parental RCC cell line, as demonstrated by its clones. This study has shown that the autologous tumor vaccine with adjuvant used here was an immunogenic therapeutic agent. The response mounted by these patients was a response to a RCC-associated antigen with the level of reactivity changing with the number of immunizations and disease status. Also suggested by this work is the possible primary tumor heterogeneity, as demonstrated by the differential reactivity seen among clones of a RCC cell line established from such a primary tumor. PMID- 4028030 TI - Staphylococcal Protein A column: correlation of mitogenicity of perfused plasma with clinical response. AB - Eleven patients with advanced breast cancer and four with astrocytoma were treated with plasma perfused over columns containing staphylococcal Protein A (SPA). Doses of 5 to 20 mg of SPA were bound to collodion charcoal particles, and this treatment resulted in partial remissions in one patient with astrocytoma and in two patients with breast cancer. Remission duration was 6 wk to 6 mo. Resolution of lymphadenopathy and a decrease in carcinoembryonic antigen were noted in an additional two breast cancer patients. Systemic reactions to infused plasma consisted of fever, chills, and rigors. In brain cancer patients, increased intracranial pressure was also noted. A mitogenic substance was generated in plasma of 11 patients after it was perfused over the SPA charcoal matrix. The mitogenic material induced lymphoproliferation comparable to concanavalin A and required the presence of SPA on the collodion charcoal but was not due to leakage of SPA from the column during plasma perfusion. Of considerable significance was that only patients whose column perfused plasma contained this mitogenic activity exhibited systemic reactions, and five of these patients obtained antitumor responses. This striking correlation implies that the mitogenic factor is an active component of SPA therapy. The ability to demonstrate mitogenicity in column perfused plasma might also be useful for selecting patients amenable to SPA therapy. These findings attest to the therapeutic value of this mode of treatment and provide an initial definition of a mediator of SPA antitumor activity. PMID- 4028031 TI - Distribution of blood group antigens A, B, H, Lewisa, and Lewisb in human normal, fetal, and malignant colonic tissue. AB - In humans, most blood group substances (BGS) are expressed throughout the fetal colon but are absent from the distal portion of adult colon. Cancers of the distal colon frequently reexpress BGS thereby suggesting that these antigens behave as oncofetal antigens at this organ site. We used a sensitive immunoperoxidase method with monoclonal antibodies directed against blood groups A, B, O (H), Lewisa and Lewisb to systematically evaluate BGS expression in fetal colon, normal adult colon from immediate autopsies of kidney donors, mucosa adjacent to cancer (transitional mucosa) and colorectal cancer tissues. In normal colon, BG-A, B, H, and Lewisb were expressed in proximal but not distal colon, whereas Lewisa was distributed uniformly throughout the colon. In colon cancer, and fetal colon, the proximal-distal gradient of BG-A, B, H, and Lewisb expression was abolished because of enhanced distal expression of these antigens. In cancer tissues, three patterns of altered BGS expression emerged: (a) incompatible expression of BG-A or BG-B (over 50% of patients); (b) deletion of BGS; and (c) precursor BG-H accumulation (80% of 25 tumors). BGS staining of transitional mucosa closely resembled that of the adjacent tumor except that no examples of BGS deletion were encountered in transitional mucosa. The goblet cell secretory vacuole accounted for most of the BGS expression in normal colon, but cancer cells demonstrated differentiation-dependent antigenic expression such that well-differentiated tumors expressed BGS on cell apical membranes and glandular contents, but poorly differentiated cancers exhibited diffuse cytoplasmic staining. These findings confirm the oncofetal nature of BGS in distal colon cancer, and provide immunohistochemical evidence for a diverse repertoire of altered antigen expression in colon cancer. Further investigation is needed to elucidate the possible genetic and biochemical mechanisms involved. PMID- 4028032 TI - Aminoglutethimide-induced hematologic toxicity: worldwide experience. AB - Marked leukopenia and/or thrombocytopenia occurred in 12 of 1333 patients treated with aminoglutethimide (0.9% incidence). Depression of blood cell counts was evident within 7 weeks of starting treatment. No delayed toxicity was encountered. Blood cell counts recovered promptly upon cessation of aminoglutethimide in all but one patient, who died from septicemia and marrow aplasia. PMID- 4028033 TI - Deep venous thrombosis during therapy for Hodgkin's disease. AB - Upon reviewing the case records of 177 patients with Hodgkin's disease, we identified ten patients (6%) with deep vein thromboses confirmed by diagnostic tests. Most of the patients initially presented with advanced Hodgkin's disease as defined by stage and constitutional symptoms. Thrombotic episodes usually occurred between cycles of chemotherapy in the absence of clinically detectable tumor. Infusion of chemotherapeutic vesicants may have contributed to the high proportion of upper extremity deep venous thrombosis in this series. Thrombotic episodes did not necessarily imply recurrent disease. Three patients developed thromboses after completion of therapy and remained free of Hodgkin's disease or other malignancies at 85+, 18+, and 17+ months of follow-up. PMID- 4028034 TI - Phase II trial of gallium nitrate in patients with advanced malignant melanoma. AB - A phase II trial of gallium nitrate (250-300 mg/m2/day for 7 consecutive days) was conducted in patients with metastatic melanoma. Therapy was well-tolerated, but only one of 31 evaluable patients experienced a partial regression. Further evaluation of gallium nitrate at this dose and schedule is not warranted in patients with malignant melanoma. PMID- 4028035 TI - Antitumor activity of trans-bis(salicylaldoximato)copper(II): a novel antiproliferative metal complex. AB - trans-Bis(salicylaldoximato)copper(II) (CuSAO2), the parent compound of a new group of antiproliferative copper(II) complexes, was studied in vivo. It had marked antitumor activity against Ehrlich ascites carcinoma in NMRI mice. Survival was considerably increased, and, in some cases, total cures were encountered. No activity against leukemia L1210 was found in female DBA/2J mice, although CuSAO2 is equally effective against L1210 and Ehrlich carcinoma cells in vitro. The side effects of CuSAO2 included weight loss, weakness, acrodynia, and blindness; all of these side effects were transient. PMID- 4028036 TI - Phase II study of recombinant alpha interferon in the treatment of advanced non small cell lung carcinoma. PMID- 4028037 TI - Phase II study of diaziquone in advanced soft tissue and bony sarcoma: a Southwest Oncology Group study. PMID- 4028039 TI - Treatment with monoclonal antibody to a Lewis lung carcinoma-associated antigen: different effects on primary tumor and its metastases. AB - The growth and dissemination of Lewis lung carcinoma have been analyzed following treatment of isolated tumor cells or of tumor-bearing animals with monoclonal antibody (MoAb) 135-13C, which recognizes a cell surface tumor-associated protein of 180,000 daltons. The results of this study indicate that MoAb 135-13C binds with high affinity to Lewis lung tumor cells and induces different effects on the primary tumor (20%-25% reduction of tumor weight) and its metastasis (twofold increase of lung nodule formation). Different schedules of MoAb 135-13C administration have shown that these effects are dose- and time-dependent. In particular, the maximum increase in metastasis formation is observed when the MoAb 135-13C is administered at time of systemic tumor dissemination. In vitro preincubation of tumor cells with MoAb prior to their iv injection into normal animals results in a significant increase of pulmonary metastatic nodules. PMID- 4028038 TI - Rate of M-component changes and plasma cell labeling index in 25 patients with multiple myeloma treated with peptichemio. AB - Twenty-five consecutive patients with previously untreated multiple myeloma were studied for bone marrow plasma cell labeling index, response to peptichemio induction therapy, and rate of M-component (MC) changes during the course of the disease. They received intermittent melphalan or cyclophosphamide as maintenance therapy and peptichemio associated with vincristine at first relapse. The response rate (76%) was independent of clinical stage, evaluated according to Merlini et al and to Durie and Salmon. Among responsive patients, rapid responders (half-life of MC decrease less than 47 days for IgA and IgG and less than 29 days for light chain myelomas) had a bone marrow plasma cell labeling index significantly higher (P less than 0.01) than that of slow responders. Rapid responders had a median survival of 15 months, while slow responders had a median survival of 42 months (P less than 0.05). The difference in survival between the two groups was accounted for mainly by the difference in duration of first response and the different rates of MC increase following it. Both of these parameters were directly related to the half-life of MC decrease at response in IgA and IgG myelomas. The duration of second response and the half-life of MC increase following it were shorter than the duration of first response and than the half-life of MC increase at first relapse. PMID- 4028040 TI - Factors modifying cytotoxicity induced by 5-FU and hydroxyurea. AB - Pretreatment of exponentially growing 9L cells for 24 hours with a nontoxic (0.77 microM) or moderately toxic (7.7 microM) concentration of 5-FU (5-FUra) enhanced cell kill induced by a subsequent 6-hour treatment with 1.3 mM hydroxyurea (HU) by a magnitude of 1 log. In confluent 9L cultures or 9L cells treated in serum free medium that decreased the cycling population, however, the 5-FUra-HU combination did not enhance the cell kill. No recovery from potentially lethal damage was observed for up to 24 hours after treatment of 9L cells with 7.7 microM 5-FUra alone or with 0.77 or 7.7 microM 5-FUra followed by 1.3 mM HU. These results show that 5-FUra and HU in combination kill cycling cells effectively and that cytotoxicity is fixed on completion of the treatment. Although the number of sister chromatid exchanges per metaphase increased significantly with increasing length of exposure to a nontoxic (0.77 microM) or moderately toxic (7.7 microM) concentration of 5-FUra, subsequent treatment with HU that resulted in cell kills of 70%-80% and 99%, respectively, did not increase the number of sister chromatid exchanges per metaphase beyond that expected from 5-FUra treatment alone. Thus, the enhanced cell kill does not appear to be a result of direct DNA damage. PMID- 4028041 TI - Combination of dacarbazine and doxorubicin in the treatment of childhood rhabdomyosarcoma. AB - The combination of dacarbazine and doxorubicin was given to 26 children with untreated rhabdomyosarcoma to determine its efficacy as front-line chemotherapy. A treatment course consisted of 250 mg/m2 of dacarbazine given iv on Days 1-5 and 60 mg/m2 of doxorubicin given iv on Day 1. After three courses of therapy, 17 patients (65%) achieved partial response and nine failed to respond. The side effects of treatment consisted of nausea, vomiting, flu-like symptoms, neutropenia associated with fever, mucositis, and thrombocytopenia (rarely). Although the response rate is comparable to other drug combinations, the lack of complete responses to the combination indicates that it is less effective as front-line therapy. PMID- 4028042 TI - G.l.c. of O-methyloxime and alditol acetate derivatives of neutral sugars, hexosamines, and sialic acids: "one-pot" quantitative determination of the carbohydrate constituents of glycoproteins and a study of the selectivity of alkaline borohydride reductions. AB - A new procedure for the quantification by g.l.c. of the carbohydrate constituents of glycoproteins is proposed which involves (a) simultaneous action of neuraminidase and neuraminic acid aldolase, (b) hydrolysis with 4M trifluoroacetic acid at 125 degrees for 1 h, and (c) conversion of the products into O-methyloxime acetates and g.l.c. The procedure has been successfully tested on fetuin, transferrin, alpha 1-acid glycoprotein, and mucin. The g.l.c. conditions used also enabled the complete separation of O-methyloxime and alditol acetate derivatives in one run, so that the release of carbohydrate chains from glycoproteins by treatment with alkaline borohydride can be investigated conveniently. There was complete release of O-linked oligosaccharides from fetuin on treatment with 0.1M NaOH/0.8M NaBH4 (68 h, 37 degrees) or 0.05M KOH/M KBH4 (24 h, 45 degrees) and also release of approximately 75% and 35-40%, respectively, of N-asparagine-linked chains. Reduced oligosaccharides were formed only from O linked chains; the mechanism by which N-linked chains were released is still not clear. PMID- 4028043 TI - N.m.r. studies of the disulphated disaccharide obtained by degradation of bovine lung heparin with nitrous acid. AB - The disulphated disaccharide IdoA(2SO3)-anManOH(6SO3) was prepared from bovine lung heparin by treatment with nitrous acid followed by borohydride reduction. The 1H- (400 MHz) and 13C-n.m.r. (100 MHz) spectra of this disaccharide derivative have been assigned completely using homonuclear spin-decoupling experiments, 13C-1H correlations, and a COSY-45 two-dimensional homonuclear correlation experiment. The 3JH,H values show that the IdoA(2SO3) residue exists in a single conformation throughout the temperature range 20-90 degrees. PMID- 4028044 TI - Bacteriophage degradation of Klebsiella K44 polysaccharide: an n.m.r. study and chemical proof of the position of the acetate group. AB - Bacteriophages (phi) have been used to degrade polysaccharides into oligosaccharides containing one or more of their repeating units. The capsular polysaccharide from Klebsiella K44 contains an acetate group, and n.m.r. spectroscopy and chemical methods have been employed to prove its linkage to O-6 of the 4-linked glucose residue. Phage phi 44 was shown to be an alpha glucosidase not influenced by the acetate moiety and thus able to depolymerize the polysaccharide into pentasaccharide repeating units, some of which contained acetate on O-6 of the reducing glucose residue. The two oligosaccharides were studied by 1H- and 13C-n.m.r. spectroscopy, and their spectra were compared with those of the native and the deacetylated polysaccharide. 13C-n.m.r. was a useful tool for locating the 6-linked acetate, the position of which was confirmed by the method of temporary protection using methyl vinyl ether. The importance of using bacteriophages to obtain oligosaccharides is highlighted by the better results obtained with the oligosaccharide in comparison to the polysaccharide, both in n.m.r. spectroscopy and the temporary protection method. PMID- 4028046 TI - A new approach to the synthesis of beta-glycosidically linked oligosaccharides containing 2-acetamido-2-deoxy-D-mannose residues. PMID- 4028045 TI - Modification of blood-borne arrest properties of lymphoma cells by inhibitors of protein glycosylation suggests the existence of endogenous lectins. AB - The requirement for intact carbohydrates of glycoproteins at the cell surface was investigated after treatment of lymphoma cells with compounds which interfere at different steps in N-linked glycosylation: swainsonine and 1-deoxynojirimycin act at different levels during the processing, so that complex oligosaccharides cannot be formed; 2-deoxyglucose, beta-hydroxynorvaline, and tunicamycin completely prevent the formation of N-linked (high-mannose as well as complex) oligosaccharides. The role of sialic acid was investigated by treating the cells with neuraminidase. These treatments resulted in altered patterns of surface labelled glycoproteins after SDS-polyacrylamide gel electrophoresis. Blood-borne arrest of lymphoma cells in the spleen was sensitive to neuraminidase and to treatments interfering with the processing of complex N-linked oligosaccharides. It is suggested that carbohydrates are signals for cellular interactions involved in the recirculation and homing behaviour of lymphoid cells and probably interact with endogenous lectins at their site of homing. PMID- 4028047 TI - Synthesis of a tri- and a hepta-saccharide which contain alpha-L-fucopyranosyl groups and are part of the complex type of carbohydrate moiety of glycoproteins. AB - Reaction of a thioglycoside with methyl trifluoromethanesulfonate (methyl triflate) in the presence of a hydroxyl compound is an efficient glycosylation method. Thus, methyl triflate-promoted condensation of ethyl 4,6-O-benzylidene-2 deoxy-2-phthalimido-1-thio-3-O-(2,3,4-tri-O-benzyl-a lpha-L- fucopyranosyl)-beta D-glucopyranoside with benzyl 3,4,6-tri-O-benzyl-alpha-D-mannopyranoside and with benzyl 2,4-di-O-benzyl-3,6-di-O-(3,4,6-tri-O-benzyl-alpha-D-mannopyranosyl)-alp ha-D- mannopyranoside gave a trisaccharide and a heptasaccharide derivative, respectively. The trisaccharide 1 and the heptasaccharide 2, which are parts of the complex type of glycoproteins, were obtained by removal of the protecting groups and N-acetylation. (formula: see text). PMID- 4028048 TI - Synthesis of a tetra- and a nona-saccharide which contain alpha-L-fucopyranosyl groups and are part of the complex type of carbohydrate moiety of glycoproteins. AB - Methyl trifluoromethanesulfonate-promoted condensation of ethyl 6-O-benzyl-2 deoxy-2-phthalimido-4-O-(2,3,4,6-tetra-O-acetyl-beta-D- galactopyranosyl)-1-thio 3-O-(2,3,4-tri-O-benzyl-alpha-L-fucopyranosyl)- beta-D- glucopyranoside with benzyl 3,4,6-tri-O-benzyl-alpha-D-mannopyranoside and benzyl 2,4-di-O-benzyl-3,6 di-O-(3,4,6-tri-O-benzyl-alpha-D-mannopyranosyl)-alp ha-D- mannopyranoside gave a tetrasaccharide and a nonasaccharide derivative, respectively. The tetrasaccharide 1 and the nonasaccharide 2 were obtained after removal of the protecting groups and N-acetylation. (formula: see text). PMID- 4028050 TI - An unusual reaction of 1,6-anhydroaldohexopyranose derivatives leading to glycals. AB - Treatment of a solution of the 2-O-(N,N-dimethylsulfamoyl) derivative 3 of the levoglucosenone-derived carbocycle 1 in liquid ammonia at -40 to -50 degrees with sodium metal gave 73% of the glycal derivative 4 instead of the expected 2-deoxy derivative (2) of 1. Under the same conditions, the 2-O-(N,N-dimethylsulfamoyl) derivatives of 1,6-anhydro-3,4-dideoxy-4-C-methyl-beta-D-ribo- and -arabino hexopyranoses gave, after acetylation, 70% of 6-O-acetyl-1,5-anhydro-2,3,4 trideoxy-4-C-methyl-D-erythro-hex-1-enit ol. In contrast, the 2-(N,N-dimethyl sulfamates) obtained from 1,6-anhydro-3,4-O-isopropylidene-beta-D-galacto- and talo-pyranose gave 6-O-acetyl-1,5-anhydro-2-deoxy-3,4-O-isopropylidene-D-lyxo-hex 1-enit ol in only low yields; the oxy substituent at C-3 may interfere with the reaction leading to the glycal. PMID- 4028049 TI - Synthesis of N-glycopeptides and a neoglycoprotein. AB - O-(alpha-D-Glucopyranosyl)-(1----6)-O-beta-D-glucopyranosyl-(1----6)-1-N (glycylglycylglycyl-L-seryl-L-leucyl-L-glutam-5-oyl)-alpha- D glucopyranosylamine has been prepared, as a model of a derivative possibly present in the glomerular basement membrane of rats, by condensation of the corresponding L-glutamyl derivative of the trisaccharide with the pentapeptide in the presence of O,O-diethyl cyanophosphonate. Protective groups were removed by O deacetylation, deethoxylation, and hydrogenolysis. The glutamyl derivative of the trisaccharide was also converted into the acyl azide which was condensed with bovine serum albumin to form a neoglycoprotein. PMID- 4028051 TI - Compartmentation of glycogen metabolism in the liver. AB - The incorporation of radioactivity into liver glycogen has been shown not only to be a metabolically inhomogeneous process but also to depend critically on the nature of the precursor. D-Galactose is incorporated into glycogen by a mechanism which is separate from that associated with the incorporation of D-glucose. D Galactose is favoured for incorporation into high-molecular-weight glycogen and consequently is affected more by treatment of the animal with the antibiotic tunicamycin, since high-molecular-weight glycogen is preferentially found in the lysosomal compartment. PMID- 4028052 TI - 1H- and 13C-n.m.r. assignments and conformational analysis of some monosaccharide and oligosaccharide substrate-analogues of lysozyme. AB - The 1H- and 13C-n.m.r. spectra of solutions of GlcNAc, beta-GlcNAc-(1----4) GlcNAc, and beta-GlcNAc-(1----4)-beta-GlcNAc-(1----4)-GlcNAc in D2O at 50 degrees are interpreted in terms of the conformations, using a combination of 1D- and 2D n.m.r. spectroscopy and spectra simulation techniques. Two preferred orientations of the hydroxymethyl group were found for each of these saccharides. The conformations have been compared with those found from X-ray crystallographic data and conformational energy calculations. PMID- 4028053 TI - Identification of the tetrasaccharide repeating-unit of the Streptococcus pneumoniae type 23 polysaccharide by high-field proton n.m.r. spectroscopy. AB - One- and two-dimensional 500-MHz 1H-n.m.r. studies of the capsular polysaccharide from Streptococcus pneumoniae type 23 have been used to determine its structure, which was confirmed by limited degradation. The proposed structure (1) differs from those suggested previously and the phosphate group has been located tentatively at position 3 of the glucosyl residue. (Formula: see text). PMID- 4028054 TI - Possible platelet activation during exercise in mitral valve prolapse patients. PMID- 4028055 TI - Diagnosis of fetal heart abnormalities by echocardiography and its significance in the obstetric and fetal management. PMID- 4028056 TI - [Diagnosis of ischemic cardiopathy by bidimensional echocardiography during transesophageal atrial pacing]. PMID- 4028057 TI - [Plasma increase of dihydroxyphenylacetic acid, a dopamine metabolite, in cardiac decompensation]. PMID- 4028058 TI - [Influence of acute changes in load on the rate of active relaxation in humans]. PMID- 4028059 TI - [Coronary disease: medical or surgical therapy?]. PMID- 4028060 TI - Biological significances in granular cells of ameloblastoma--histochemical identification of sugar residues and filamentous proteins, morphometry and DNA cytometry of granular cells. PMID- 4028061 TI - Metabolic studies as a diagnostic measure for cancer--I. Adenocarcinomas of different organs, especially the human mamma. PMID- 4028062 TI - Changes in chromatin structure and transcription activity by starvation and dietary sucrose in mature and immature intestinal epithelial cells of the rat. PMID- 4028064 TI - Studies on fresh water snails, specific intermediate hosts for schistosomiasis- III. Isolation of total proteins from chemically pretreated snails. PMID- 4028063 TI - Circadian and seasonal rhythm of beta-glucuronidase in rat liver. PMID- 4028065 TI - [Effect of various effectors on alkaline phosphatase of beef kidney]. PMID- 4028066 TI - The role of brain extracellular proteins in neuroplasticity and learning. AB - Double labeling studies of the pattern of protein synthesis in goldfish and mouse brain identified a class of glycoproteins (the ependymins) whose turnover rate was enhanced after training. A variety of control experiments indicated that these macromolecules have an important role in the molecular and cell biology of learning. Antisera to the ependymins when injected into the brains of trained goldfish cause amnesia of a newly acquired behavior. Isolation and localization studies by immunocytochemical methods indicate that the ependymins are released into the brain extracellular fluid by a class of neurosecretory cells. In mammalian brain ependymin-containing cells are highly concentrated in the limibic system. The ependymins are constituted from two disulfide-linked acidic polypeptide chains (M.W.37K and 31K). They contain at least 5% covalently bound carbohydrate per chain with mannose, galactose, N-acetylglucosamine and N acetylneuraminic acid as the predominant components. The highly soluble ependymins can rapidly polymerize to form an insoluble fibrous matrix if calcium is removed from solution by the addition of a Ca2+-chelating agent or dialysis. The self-aggregation property of the ependymins can be triggered by the depletion of Ca2+ from the extracellular space. Studies of the kinetics of the aggregation phenomenon by measurements of turbidity changes indicate that the process can be terminated but not reversed by restoring Ca2+ to its normal CSF level. Immunohistochemical studies of the brains of trained goldfish show the presence of punctate statining sites in the perimeter of certain cells located in specific brain regions. This suggests that ependymin aggregation might occur in vivo during learning. A molecular hypothesis relating the aggregation properties of the ependymins to neuroplasticity and learning is proposed. PMID- 4028067 TI - [An infectious origin of schizophrenia?]. PMID- 4028068 TI - [Comparison of the loading test and the histamine test in patients with bronchial asthma]. PMID- 4028069 TI - [The effect of cholinergic and histaminergic receptor block and prostaglandin synthesis inhibition on the secretion of growth hormone after glucagon]. PMID- 4028070 TI - [The elimination of a man from paternity on the basis of the HLA system in a family study]. PMID- 4028071 TI - [The importance and the mission of medical historiography]. PMID- 4028072 TI - [Ayurveda--the traditional Indian medical system]. PMID- 4028073 TI - [Possibilities and limitations of psychotherapy under the conditions of intensive care units]. PMID- 4028074 TI - [Prognostic value of the early stress test and the significance of indicators in the electrocardiogram at rest in patients with myocardial infarct]. PMID- 4028075 TI - [Deep hypothermia with temporary circulatory arrest in the surgery of congenital heart defects in small children. I. Biochemical changes in the blood and urine]. PMID- 4028076 TI - [Deep hypothermia with temporary circulatory arrest in the surgery of congenital heart defects in small children. II. Functional changes during surface cooling. Total oxygen consumption during extracorporeal circulation]. PMID- 4028077 TI - [Hematologic changes after a nuclear explosion]. PMID- 4028078 TI - [Prospective study of lung cancer in hospitalized patients. I. Basic data on 618 patients]. PMID- 4028079 TI - [Assessing drug effects]. PMID- 4028080 TI - [The effect of decreased intrathoracic pressure on systolic time intervals in patients with ischemic heart disease]. PMID- 4028081 TI - [The 47,XXX syndrome in a family with the fragile X chromosome syndrome]. PMID- 4028082 TI - [Experimental model of splanchnic lymphostasis. Induction of chronic pancreatopathy]. PMID- 4028083 TI - [The protected coagulum method--the basis for rational chemoprophylaxis in surgery]. PMID- 4028084 TI - [Possibilities of protecting the ischemic focus in the myocardium]. PMID- 4028085 TI - [The mission of the information unit in a scientific research institute]. PMID- 4028086 TI - [Noninvasive diagnosis of pulmonary hypertension]. PMID- 4028087 TI - [Diabetes mellitus and the eye]. PMID- 4028088 TI - [The significance of computer tomography in the differential diagnosis of septic fevers]. PMID- 4028089 TI - [Preventive parasitologic examination of university students as part of taeniarhynchosis control]. PMID- 4028090 TI - [Theophylline drugs with a prolonged (depot) effect]. PMID- 4028091 TI - [The role of the physicians in the formation of attitudes by the population regarding questions of the environment]. PMID- 4028092 TI - [Prospective study of lung cancer in hospitalized patients. III. Prognosis of patients in relation to the radiographic picture]. PMID- 4028094 TI - [Morphology and medicine]. PMID- 4028093 TI - [Statistical evaluation of creatinine and urea excretion in patients in critical condition]. PMID- 4028095 TI - [Nitrosamines--potential carcinogens?]. PMID- 4028096 TI - [Initial experience in the treatment of systemic lupus erythematosus using plasmapheresis]. PMID- 4028097 TI - [2 years' experience with the treatment of symptomatic liver porphyria with pyrimethamine]. PMID- 4028098 TI - [Hemo-obstructive ileus in secondary pancytopenia]. PMID- 4028099 TI - [Neurotoxicity--an old and new threat to mankind]. PMID- 4028100 TI - [Diagnosis of cerebral ischemic malacia using computer tomography (CT)]. PMID- 4028101 TI - [The diagnosis and clinical significance of the empty sella syndrome]. PMID- 4028102 TI - [IgG synthesis in the central nervous system in multiple sclerosis and other neurologic diseases. Measurement and validity]. PMID- 4028104 TI - [What is UNICEF?]. PMID- 4028103 TI - [24-hour whole-body retention of 99mTc-diphosphonate. Another method for osteological examination]. PMID- 4028105 TI - [Terms with the component -pathia]. PMID- 4028106 TI - Mitotic response to wounding in goitrous and normal rat thyroid: implications for thyroid growth control. AB - Thyroid growth in the rat in response to a sustained elevation of serum thyrotropin (TSH) is limited by a progressive desensitization of the follicular cells to the mitogenic action of TSH which is not reversed by withdrawal of stimulation or by reduction of cell number. This study shows that, in thyroids which have reached a 'plateau' of growth, wounding induces a marked local follicular cell mitotic response which is equal in magnitude to that seen in control glands. This demonstrates that these cells, which are refractory to TSH, have not lost the capacity to divide. It is concluded that limitation of TSH induced thyroid growth is not due to a non-specific loss of mitotic capacity resulting from severe hypothyroidism or goitrogen toxicity, or to an inherent limitation of the number of divisions which a follicular cell can undergo. The implications of these findings are discussed. PMID- 4028107 TI - Effect of trifluoperazine on DNA synthesis during liver regeneration. AB - An intraperitoneal injection of the calcium-calmodulin blocker trifluoperazine into rats at 4 hr after a partial hepatectomy produced a strong inhibition of DNA synthesis observed at 24 hr after surgery; but when injection was administered at 20 hr after hepatectomy, it did not produce any effect on DNA replication. These observations indicate that trifluoperazine acted by blocking one or more events involved in triggering DNA replication but it did not affect on-going DNA synthesis. A more detailed study indicated that when trifluoperazine was injected at 4 hr after surgery, a 12 hr delay in the cytosolic calmodulin surge observed between 6 and 12 hr after partial hepatectomy (previous to initiation of DNA replication) and also in the starting of DNA synthesis was produced. These findings suggest that the pre-replicative surge of cytosolic calmodulin could be involved in triggering DNA synthesis observed after partial hepatectomy. PMID- 4028108 TI - Self-renewal capacity and clonal succession of haemopoietic stem cells in long term bone marrow culture. AB - The CFU-s proliferative potential varied greatly during long-term cultivation. Most of the CFU-s in the cultures were represented by cells with low renewal capacity. Pre-CFU-s cells capable of producing multipotential colonies in methylcellulose, which contained CFU-s with a high proliferative potential, were identified in the culture. In cultivation of a mixture of cells of different karyotype their ratio changed rapidly from week to week. The findings were consistent with the hypothesis that haemopoietic stem cells are maintained in the culture by the products of a small number of clones which arise and decline in succession, and that pre-CFU-s, but not the CFU-s themselves, are clonogenic progenitors. PMID- 4028109 TI - Effect of vinblastine on the cell cycle and migration of ameloblasts of mouse incisors as shown by autoradiography using 3H-thymidine. AB - The effects of vinblastine on the cell cycle and the migration of ameloblasts were studied in the lower incisors of mice by labelling the cells with 3H thymidine ([3H]TdR) and radioautography. A group of mice received 2 micrograms/g of body weight vinblastine intraperitoneally and 6 hr after these animals and those of a control group were injected with 1 microCi/g body weight of [3H]TdR, and sacrificed at time intervals from 0.75 hr to 15 days. The generation time of ameloblasts in the progenitor compartment was 14.8 hr in animals treated with vinblastine and 17 hr in the controls, using the FLM curve method; with the grain dilution method the duration was respectively 29.25 hr and 25.96 hr. The thymidine labelling index of the treated animals was 50% higher than the controls. The velocity of ameloblast migration, determined either by the displacement of the most incisally labelled cell or by the grain dilution method, was lower in the experimental group (2.48 cell positions/hr and 9.18 microns/hr respectively) as compared with the control (3.21 cell positions/hr and 18.88 microns/hr respectively). The results on the ameloblast production rate are contradictory but the slowing down in the velocity of cell migration is compatible with a decrease of the rate of cell production in the progenitor compartment as a vinblastine effect. PMID- 4028110 TI - Mesenteric lymphoblast localization throughout the murine small intestine: temporal analysis relating intestinal length and lymphoblast division. AB - Mesenteric lymphoblasts (MLN) have a predilection to selectively localize in the lamina propria and epithelium of the small intestine. Using an adoptive transfer method, we examined the localization kinetics of these blasts in the intestinal wall with respect to their distribution from duodenum to terminal ileum and also assessed their mitotic activity by autoradiographic techniques. 3H-thymidine labelled MLN cells were found throughout the small intestine by 6 hr post transfer and reached a maximum frequency in this organ by 24 hr post-transfer. Donor blasts were most frequent in the duodenum and terminal ileum regions of the gut. Subsequently, the frequency of labelled cells throughout the intestinal wall declined to near zero. The apparent accumulation of MLN blasts in the gut was not related to either a temporary retention and departure from the pulmonary vasculature or to mitotic division of labelled cells in the gut wall. A model describing the relationship between MLN blast localization kinetics in various segments of the intestine was formulated. PMID- 4028111 TI - Analysis of cell types identifiable in air-dried cell preparations of human testis. AB - The mixed cell population of the testicular epithelium has been studied in air dried cell preparations obtained from a testicular biopsy. Observed cell types are defined, quantified and assigned to cell stages of the spermatogenic cycle. Studies with tritiated thymidine helped to categorize the spermatogonial cell types. Variation in cell size within cell categories, variation in frequency of cells in different categories within individuals, and variation in frequency of cells within categories between individuals were subjected to quantitative analysis. PMID- 4028112 TI - Graphical method for analysing stathmokinetic data. AB - The accumulation of cells in G2M measured flow cytometrically follows a straight line when plotted against time in colcemid with the transform ln (1 + fG2M), where fG2M is the fraction of cells in the G2M peak. Extending this function to the value, ln 2, will locate a point B. Drawing a line from point B to ln 1 perpendicular to the abscissa, will locate point A at the initial value of ln (1 + fG2M). A line from ln 2 at t = 0 through point A will intersect the abscissa at the cell doubling time. Application of this method to the depletion of G1 cells is also possible. PMID- 4028113 TI - Liver DNA synthesis after phenytoin injection in adult NMRI mice. AB - Stimulation of hepatocyte DNA synthesis was observed in adult mice, as measured by the number of parenchymal cells in S phase, at two different times after a single i.p. injection of diphenylhydantoin (DPH): 18 and 25 hr. No such stimulation was obtained for Kupffer or endothelial cells. PMID- 4028114 TI - Differential permeability of pineal capillaries to lanthanum ion in the rat (Rattus norvegicus), gerbil (Meriones unguiculatus) and golden hamster (Mesocricetus auratus). AB - Capillaries in the pineal gland of the rat (Rattus norvegicus), gerbil (Meriones unguiculatus) and golden hamster (Mesocricetus auratus) were investigated by means of electron-microscopical tracer studies using lanthanum. The tracer was administered together with the fixative solution by perfusion via the left cardiac ventricle. In the rat, endothelial junctions of fenestrated capillaries are permeable to lanthanum. In the gerbil the tracer does not leave the capillaries, which are of the non-fenestrated type throughout the organ. In the golden hamster the two portions of the pineal system have different types of capillaries. While in the superficial pineal fenestrated capillaries permeable to lanthanum predominate, the deep pineal possesses capillaries that are, without exception, devoid of fenestrations and impermeable to the tracer. It is suggested that differences in the structure of the capillaries are related to differences in the extent of a specialized contact of the pineal gland to the third ventricle. PMID- 4028115 TI - Contact behaviour exhibited by migrating neural crest cells in confrontation culture with somitic cells. AB - When grown in confrontation culture on a planar substratum, avian neural crest cells and somite cells display both homotypic and heterotypic contact inhibition of movement as judged by analysis of time-lapse video recordings of locomotory and contact behaviour, and by use of a nuclear overlap assay. It is therefore unlikely that migration of neural crest cells within the embryo, and within embryonic tissues, can be explained on the basis of a lack of contact inhibition. The results are discussed in the general context of cell invasiveness. PMID- 4028116 TI - Morphometry of muscle fibre types in the carp (Cyprinus carpio L.). Relationships between structural and contractile characteristics. AB - Ultrastructural parameters of muscle fibre types of the carp (Cyprinus carpio L.) were measured and compared with their contractile properties. In red fibres, which are slower than pink fibres, the relative length of the junction between the T system and the sarcoplasmic reticulum (T-SR junction) is smaller and the Z lines are thicker than in pink fibres. Pink fibres have a smaller relative length of T-SR junction than white fibres from the axial muscles. The two types of red fibres present in carp muscle also differ in their relative lengths of T-SR junction. Significant differences in the relative areas of the SR were not found. The relative volume of myofibrils in red fibres is two-thirds that in pink fibres, a difference that is not reflected in the maximal isometric tetanic tensions of these types. Red fibres, which are less easily fatigued than pink fibres, have larger relative volumes of subsarcolemmal and intermyofibrillar mitochondria. Small pink fibres have a larger relative volume of subsarcolemmal mitochondria than large pink fibres, but have a similar relative volume of intermyofibrillar mitochondria. Small and large pink fibres differ in the relative volumes of their membrane systems, but have similar relative lengths of T-SR junction. PMID- 4028117 TI - 1-Methylguanine and 7-methylguanine increase cell agglutinability. AB - 1-Methylguanine and 7-methylguanine, both metabolic products of tRNA degradation, are known to induce transformation of Chinese hamster fibroblasts in culture. The effects of these compounds on the cell membrane have been studied by the method of Concanavalin A-mediated hemadsorption. 1-Methylguanine or 7-methylguanine induced a 50% increase of Con A-mediated hemadsorption within 20 hours of exposure of the cells to the agent at a concentration of 10(-5) M. This alteration was reversed within 13 days when the cells were grown in the control medium. Prolonged treatment with 1-methylguanine or 7-methylguanine resulted in changes which were only slowly reversed during growth of the cells in the control medium. The effect of the methylated purines on the cell membrane could be completely inhibited by simultaneous addition of dibutyryl-cAMP at a concentration of 10(-5) M. The possible mechanism of cell membrane alteration by methylated purines and its relevance to transformation in vitro are discussed. PMID- 4028118 TI - Embryonic rat adrenal glands in organ culture: effects of dexamethasone, nerve growth factor and its antibodies on pheochromoblast differentiation. AB - In the present study we sought to determine the developmental potentialities and restrictions of adrenal medullary cells (pheochromoblasts) by investigating their morphological and biochemical response to nerve growth factor (NGF), anti-NGF antibodies and dexamethasone (DEX) after explantation into culture at different embryonic stages. With the exception of explants taken at embryonic day 15 (E 15) cultures of embryonic adrenal glands showed neurite outgrowth, which was not influenced by the addition of NGF, anti-NGF antibodies or DEX to the culture medium during the 4-day-culture period. Pheochromoblasts in E 17 + 4 explants showed spontaneous ultramorphological and biochemical maturation in terms of an increase in the number of catecholamine storage vesicles (CSVs) per micron 2 of cytoplasmic area, diameters of the cores of CSVs, percentages of electron-lucent cores of CSVs indicative of increased storage of adrenaline, overall catecholamine (CA) content and relative amount of adrenaline. NGF did not significantly affect this maturational process. Anti-NGF antibodies slightly decreased the proportion of adrenaline. The most pronounced maturation was seen in response to DEX and DEX plus NGF, although a maturational state equivalent to the E 21 stage was not achieved. E 21 + 4 explants showed neither spontaneous nor drug-induced biochemical maturation. Medullary cells in NGF-treated E 21 explants frequently retained the morphological features of pheochromoblasts. Treatment with anti-NGF antibodies significantly reduced the portion of adrenaline as compared to any other treatment. We conclude that under the culture conditions employed (1) a few pheochromoblasts spontaneously express a neuronal phenotype, (2) differentiation of pheochromoblasts towards chromaffin cells is enhanced by glucocorticoids but not by NGF, and (3) anti-NGF antibodies do not impair spontaneous neuritic growth and morphological maturation of pheochromoblasts, but cause a small reduction in the relative amount of adrenaline. PMID- 4028119 TI - Stannius corpuscles and plasma calcium levels during the reproductive cycle in the cichlid teleost fish, Oreochromis mossambicus. AB - The corpuscles of Stannius (CS) of the cichlid Oreochromis mossambicus (formerly Sarotherodon mossambicus) were studied in relation to sexual maturation and plasma calcium levels. After sexual maturation, the CS are enlarged in female fish, because of an increase in size and number of the type-1 cells. During the ovarian cycle, the size of the CS increases in parallel with the growth of the ovaries. Concurrently, plasma total calcium increases markedly until spawning. This increase is mainly accounted for by calcium bound to proteins (vitellogenins), but the ultrafiltrable calcium fraction is also slightly higher than in males. Ovariectomy is followed by a reduction in the size of the CS, mainly a result of involution of the type-1 cells, and by a reduction in plasma calcium to levels typical for males. Gonadectomy in males does not affect size or ultrastructure of the CS, or plasma calcium levels. Since the type-1 cells of the CS are the presumptive source of a hypocalcemic hormone, we conclude that activation of the CS during the female reproductive cycle is a response to elevated calcium levels that accompany ovarian maturation. We suggest that the CS respond in particular to the elevated ultrafiltrable or ionic calcium levels. PMID- 4028120 TI - Structure of tendon organs of the rat after neonatal de-efferentation. AB - The number, size and structure of tendon organs were examined in leg muscles of the rat 3-19 weeks after de-efferentation performed in newborn animals by removal of the lumbosacral spinal cord. After this operation, tendon organs differentiated and grew in disused muscles and were innervated by primary sensory neurons, the dorsal roots of which had been disrupted. Three weeks after de efferentation extensor digitorum longus muscles contained 14.1 +/- 1.0 (mean +/- standard error) and soleus muscles had 14.2 +/- 1.6 tendon organs, which corresponds to the mean number of tendon organs in the respective control muscles. The mean size of tendon organs was, however, changed. Tendon organs became on the average by 53% longer and by 35% thinner in de-efferented extensor digitorum longus muscles that were prolonged due to immobilization, as compared with shorter and wider tendon organs in de-efferented soleus muscle that remained in the shortened position. The ultrastructural differentiation of tendon organs was completed after the operation as under normal conditions. Thus it can be concluded that elimination of muscle function during the period of postnatal development indirectly affects the mean size of these receptors, but does not otherwise interfere with their morphogenesis. PMID- 4028121 TI - Coupling of gap junctions by induction of impulse conductivity in cultured epithelium of newt embryo (Cynops orientalis). AB - Impulse generation and propagation was previously shown to occur in skin epithelium of newt (Cynops orientalis) embryos during certain stages of development and to be correlated with morphological changes of gap junctions. These properties are not detected in embryonic epithelia explanted and grown in culture. However, early explants when transplanted to a host embryo develop conductivity, and relatively large gap junctions with loose arrangement of connexons occur as soon as the host embryo reaches the stage when conductivity is at its maximum. In contrast, morphological and physiological characteristics of impulse propagation are lost when the transplanted epithelium is extirpated from the host embryo and returned to in-vitro conditions. Therefore, it appears that impulse propagation is dependent not solely on the differentiation of epithelial cells but upon signals from non-epithelial (possibly mesodermal) tissue as well. PMID- 4028122 TI - Interneuronal and glial-neuronal gap junctions in the lamina ganglionaris of the compound eye of the housefly, Musca domestica. AB - The cell-body layer of the lamina ganglionaris of the housefly, Musca domestica, contains the perikarya of five types of monopolar interneuron (L1-L5) along with their enveloping neuroglia (Strausfeld 1971). We confirm previous reports (Trujillo-Cenoz 1965; Boschek 1971) that monopolar cell bodies in the lamina form three structural classes: Class I, Class II, and midget monopolar cells. Class-I cells (L1 and L2) have large (8-15 microns) often crescent-shaped cell bodies, much perinuclear cytoplasm and deep glial invaginations. Class-II cells (L3 and L4) have smaller perikarya (4-8 microns) with little perinuclear cytoplasm and no glial invaginations. The 'midget' monopolar cell (L5) resides at the base of the cell-body layer and has a cub-shaped cell body. Though embedded within a reticulum of satellite glia, the L1-L4 monopolar perikarya and their immediately proximal neurites frequently oppose each other directly. Typical arthropod (beta type) gap junctions are routinely observed at these interfaces. These junctions can span up to 0.8 micron with an intercellular space of 2-4 nm. The surrounding nonspecialized interspace is 12-20 nm. Freeze-fracture replicas of monopolar appositions confirm the presence of beta-type gap junctions, i.e., circular plaques (0.15-0.7 micron diam.) of large (10-15 nm) E-face particles. Gap junctions are present between Class I somata and their proximal neurites, between Class I and Class II somata and proximal neurites, and between Class II somata. Intercartridge coupling may exist between such monopolar somata. The cell body and proximal neurite of L5 were not examined. We also find that Class I and Class II somata are extensively linked to their satellite glia via gap junctions. The gap width and nonjunctional interspace between neuron and glia are the same as those found between neurons. The particular arrangement and morphology of lamina monopolar neurons suggest that coupling or low resistance pathways between functionally distinct neurons and between neuron and glia are probably related to the metabolic requirements of the "nuclear" layer and may play a role in wide field signal averaging and light adaptation. PMID- 4028123 TI - Acyltransferase and acid hydrolase activities of the abalone photoreceptor cell. AB - In order to study the synthesis and degradation processes of the photoreceptor membranes in the abalone, Nordotis discus, the localization of acyltransferase and acid hydrolase activities, respectively, were determined at the electron microscopic level. Acyltransferase activity was localized on the cytoplasmic sides of thick (greater than 10 nm) membranes of the following organelles: a few cisternae at the trans (or concave) side of Golgi apparatus, Golgi and probably related vesicles, short tubules, curved pentalaminar disks and limiting membranes of the phagosomal multivesicular bodies; all organelles were scattered in the peri- to supranuclear cytoplasm. The phospholipids, which are major components of the photoreceptor membrane, are considered to be synthesized by these membranes. Acid phosphatase activity was localized in the lumina of Golgi cisternae and vesicles, lysosomes, and smaller multivesicular and related bodies, but not in multilamellar bodies. The matrices of the larger multivesicular bodies and of the pigment granule complexes showed arylsulfatase activity. Vesiculated and autophagocytosed photoreceptor microvilli seemed to be degraded by acid hydrolases, forming multivesicular and related bodies. Supporting cells also showed acyltransferase and acid hydrolase activities. PMID- 4028124 TI - Carbohydrate-binding proteins of tumor lines with different growth properties. I. Differences in their pattern for three clones of rat fibroblasts transformed with a myeloproliferative sarcoma virus. AB - Three clones of myeloproliferative virus (MPV)-transformed rat fibroblasts (NRK) with different growth properties and morphology were transplanted to athymic nude mice. Presence of carbohydrate-binding proteins was inferred by fluorescence microscopy using fluorescent, glycosylated markers. Salt and detergent extracts of tumors from this model system were fractionated under identical conditions on different sets of Sepharose columns, to which lactose, asialofetuin, melibiose, mannan and fucose had been covalently linked. Successive elution by chelating reagent and specific sugar resulted in isolation of the different Ca2+ -dependent and Ca2+ -independent endogenous carbohydrate-binding proteins that were assayable as agglutinins. In comparison, the different tumors displayed a pattern with qualitative and quantitative alterations. Since protein-carbohydrate interaction mediated by carbohydrate-binding proteins (lectins) is of importance for cognitive processes, it is remarkable that the pattern of membrane glycoproteins, isolated by affinity chromatography on resins with immobilized plant lectins, had also been found to reveal certain individual properties for receptors specific for peanut agglutinin (PNA) and Ulex europaeus agglutinin (UEA). These demonstrated differences within the system of protein-carbohydrate interaction suggest that endogenous lectins and their ligands have potential significance as markers defining a certain phenotype within this tumor model system. PMID- 4028125 TI - Nerve fiber production by intraocular adrenal medullary grafts: stimulation by nerve growth factor or sympathetic denervation of the host iris. AB - This study evaluates the production of adrenergic nerve fibers by adrenal medullary tissue of the adult rat grafted to the anterior chamber of the eye of adult recipients. The chromaffin grafts attach to and become vascularized by the host iris. They decrease in size intraocularly during the first 3 weeks. This decrease is somewhat counteracted by sympathetic denervation of the host iris, and better counteracted by sympathetic denervation and addition of nerve growth factor (NGF, given at grafting and 1 and 2 weeks after grafting). Outgrowth of adrenergic nerve fibers from the grafts into the host iris was studied in wholemount preparations by use of the Falck-Hillarp technique 3 weeks after grafting. The innervated area of the host iris was approximately doubled in the chronically sympathectomized group and doubled again in the chronically sympathectomized NGF-supplemented group. Chronic sympathetic denervation had no effect on density of outgrowing nerves, whereas addition of NGF more than doubled nerve density. Since sympathetic denervation causes a slight elevation of NGF activity in the iris, the present experiments are taken as evidence that the level of NGF in the iris regulates formation of nerve fibers by adrenal medullary tissue grafts from adult rats. PMID- 4028126 TI - Scanning electron-microscopic studies on the three-dimensional structure of mitochondria in the mammalian red, white and intermediate muscle fibers. AB - The three-dimensional structure and arrangement of mitochondria in the red, white and intermediate striated muscle fibers of the rat were examined under a field emission type scanning electron microscope after removal of cytoplasmic matrices by means of the Osmium-DMSO-Osmium procedure. Beneath the sarcolemma, spherical or ovoid subsarcolemmal mitochondria show accumulations. The mitochondria are numerous and large in size in the red fibers, intermediate in the intermediate fibers, and few and small in the white fibers. Paired, slender I-band-limited mitochondria were located on both sides of the Z-line and partly embraced the myofibrils at the I-band level; they occurred in all three types of fibers. In the intermyofibrillar spaces, numerous mitochondria formed mitochondrial columns. These columns were classified into two types: 1) thick mitochondrial columns, formed by multiple mitochondria each with an intermyofibrillar space corresponding to one sarcomere in length, and 2) thin mitochondrial columns, established by single mitochondria corresponding to one sarcomere in length. In the red fibers mitochondrial columns were abundant and the ratio of the thick and thin columns was almost the same, while in the intermediate fibers most of the columns belonged to the thin type. The white fibers displayed rare, very thin columns. PMID- 4028127 TI - Separation of leucocytes in the dogfish (Scyliorhinus canicula) using density gradient centrifugation and differential adhesion to glass coverslips. AB - The blood of the dogfish, S. canicula, contains several types of leucocytes, namely thrombocytes, monocytes, lymphocytes and four populations of granulocytes. Three of these granulocyte types, G1, G3 and G4, are eosinophilic while G2 is heterophilic/neutrophilic. All of the leucocyte types, with the exception of G2 granulocytes and monocytes, can be separated by means of their differential adherent properties to glass and by density gradient centrifugation. Thrombocytes, G3 and G4 granulocytes can be separated in good purity by single step methods while G1 granulocytes and lymphocytes require a combination of density gradient centrifugation followed by adherence to glass to remove contaminating thrombocytes. Depending on the cell type, between 11-45% of cells with consistently high viability can be recovered after separation. Separated populations of the thrombocytes and granulocytes will be especially useful for studies on the role of such cell types in inflammation. PMID- 4028128 TI - Endocytic pathways and time sequence of lysosomal transfer of macromolecules in cultured mouse peritoneal macrophages. Double-labeling experiments with horseradish peroxidase and ferritin. AB - A double-labeling protocol was used to study endocytic pathways and lysosomal transfer of exogenous macromolecules in cultured mouse peritoneal macrophages. After pulse-chase labeling of lysosomes with horseradish peroxidase (visualized cytochemically), the cells were exposed to native, anionic ferritin for 0-45 min at 37 degrees C and then analysed by transmission electron microscopy. The results show that ferritin binds to the plasma membrane, accumulates in coated pits, and is rapidly taken up in small, smooth-surfaced endocytic vesicles. The latter carry the ferritin molecules directly to lysosomes, recognized by their peroxidase labeling, or fuse with each other to form larger endocytic vacuoles (endosomes) which in turn fuse with and empty their content into lysosomes. The first signs of transfer of ferritin into the lysosomes were seen after 5-10 min of exposure and after 25-30 min most of the lysosomes were labeled. Union of ferritin-labeled and other lysosomes was also noted, suggesting that the contents of the lysosomes were spread within the lysosomal compartment by fusion-fission processes. It is concluded that a multiplicity of structures is involved in the uptake and intracellular transport of exogenous macromolecules in macrophages and that the time sequence of lysosomal transfer of the interiorized material is highly variable. PMID- 4028129 TI - Variations in capillary permeability from apex and crypt in the villus of the ileo-jejunum. AB - The permeability of fenestrated capillaries in an organ is believed to be homogeneous. However, the permeability of fenestrated capillaries in different organs and to various exogenous tracers varies from a complete restriction, as found in the eye (Pino and Essner 1980, 1981; Pino 1985a) to the freely permeable peritubular capillaries of the kidney (Venkatachalam and Karnovsky 1972). In the present report we demonstrate that within any single intestinal villus from the ileo-jejunum of the rat, the permeability of fenestrated capillaries is not uniform. Exogenous hemoglobin (Einstein-Stokes radius [ESR] = 3.2 nm) exists all capillaries at any villar level in less than 5 min. In contrast, all villar capillaries restrict catalase (ESR = 5.2 nm) at 5 min, but by 60 min the tracer is present extravascularly in crypt and lower villar regions. Apical capillaries are slightly permeable to catalase at 2 h, but the bulk of the tracer remains in the lumina. The particulate tracer ferritin (ESR = 6.1 nm) is restricted 3-10 times more by apical capillaries than basal ones and is found in increasing concentration extravascularly at lower villar and crypt levels after 20 min. Following an 18-h circulation, a second dosage of ferritin is restricted by the endothelium at all villar levels. Immunocytochemical localizations of the plasma proteins albumin (ESR = 3.5 nm) and IgG (ESR = 5.5 nm) revealed an apparent lack of restriction at all villar levels. These results demonstrate that apical villar capillaries in the ileo-jejunum are more restrictive to exogenous molecules with ESR greater than or equal to 5.2 nm. Also, the passage of tracer molecules out of an endothelium alters the subsequent permeability of that vessel. PMID- 4028130 TI - Three-dimensional organisation of the vasculature of the rat spermatic cord and testis. A scanning electron-microscopic study of vascular corrosion casts. AB - The vascular architecture of the rat testis and spermatic cord was studied by a corrosion cast technique combined with scanning and transmission electron microscopy, and light microscopy. The casts preserve the endothelial impressions of the vessels and enable them to be differentiated into the various vascular components. Frequent arterio-arterial anastomotic arcades and occasional arteriovenous anastomotic channels are seen. A well defined hexagonal pattern of intertubular and peritubular vessels surround the seminiferous tubules. Prominent large endothelial nuclei protrude into the arterial lumina at branching sites, but their functional significance is not known. The outer-most vascular layer of the testis consists of large veins, venules, and capillaries, but lacks any arterial branches; it also contains loosely arranged veno-venous anastomotic networks. We have named this vascular layer the sub-albugineal venous plexus. The testicular artery increases in luminal diameter as it approaches the testis. The periarterial capillary plexus, which lies between the pampiniform plexus and the testicular artery, is drained by two types of venules. PMID- 4028131 TI - Quinacrine-induced dilation of the rat cecum and degeneration of large granular vesicle-containing neurons in the myenteric plexus. AB - Intraperitoneal injection of quinacrine (100 mg/kg) into rats causes marked dilation of the cecum about one week after the injection, but the jejunum remains its normal size. The morphological changes induced in the myenteric plexus and the longitudinal and circular muscle layers of both the cecum and the jejunum have been examined by fluorescence and electron microscopy 1.5 h to 2 weeks after the injection. In the cecum, 1.5 h after the injection, the granular fluorescence of quinacrine was apparent in many ganglion cells of the myenteric plexus and in the nerve fibers in the muscle layers. In connection with the granular fluorescence, numerous lysosomal dense bodies appeared in ganglion cells and axons, and subsequently the degeneration of the neurons was observed at ultrastructural level. The lysosomal dense bodies often contained many large granular vesicles of 95-140 nm in diameter. The number of lysosomal dense bodies in the axons was greatest 3-7 days after the injection. Although the axon type sensitive to quinacrine could not be specified, axons containing many large granular vesicles were the predominate type. Fibrosis in the outer longitudinal muscle layer was another characteristic resulting from quinacrine administration. Proliferation of the rough-surfaced endoplasmic reticulum and of the Golgi complex and a concomitant decrease in the number of myofilaments became evident in many smooth muscle cells 3-7 days after the injection; the intercellular spaces became enlarged 7 days after quinacrine administration. These changes and the dilation of the cecum showed considerable recovery 2 weeks after the injection.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4028132 TI - Cytochemical localization of alkaline phosphatase in the ependyma of the rat medulla oblongata. AB - The ependyma of the IVth ventricle and the central canal of the rat medulla oblongata was investigated using the cytochemical technique for alkaline phosphatase (A1Pase) which revealed two types of ependymal cells in the medulla. The central canal type of the ependymal cell occupying the dorsal part of the central canal in the lower medulla exhibited intense A1Pase activity with light microscopy. These cells had reaction products in all plasma membranes, including the microvilli and the cilia at the luminal cell surface. Some cells appeared to be tanycytes, since the process reached the basement membrane of the parenchymal blood vessel. The ventricular type of ependymal cells, which form the floor of the IVth ventricle and the central canal, contained no reaction products in any structure of the luminal cell surface. The possible relationship between the cerebrospinal fluid and the nervous tissues through the ependymal linings is discussed. PMID- 4028134 TI - Blood supply of the bed nucleus of the stria terminalis in rat. AB - The topographical distribution of the blood vessels in the bed nucleus of the stria terminalis (NIST) has been mapped in rats. Arteries and veins were visualized in red and blue by using a double-ink perfusion technique. Arteries supplying the NIST arise from the anterior cerebral artery directly or through the anterior communicating and interhemispheric arteries. Only a few, dorsal branches derive from the medial cerebral artery through thalamostriatal arteries. According to their terminal branches, NIST arteries can be divided into five groups: medial, ventral, lateral, septal and dorsal, which have only a relatively small overlap in their territories. About 90% of veins from the NIST drain into the major basal veins. Medial branches run into the perioptic and interhemispheric veins, while the ventral branches and the large lateral vein drain directly into the anterior cerebral vein. A small proportion of NIST veins run dorsalward into the vena cerebri magna via thalamostriatal veins. PMID- 4028133 TI - Granule populations in oxytocin and abnormal perikarya of the supraoptic nucleus of homozygous Brattleboro rats: effects of colchicine administration. AB - Magnocellular neurones in the supraoptic nucleus of the homozygous Brattleboro rat, which are unable to produce vasopressin, were investigated by immunocytochemistry to identify both the oxytocin cells and the abnormal neurones, which in normal animals would produce vasopressin. The abnormal cell profiles were significantly more rounded than those of the oxytocin cells. Both cell types showed evidence of hyperactivity, but the Golgi apparatus was more extensive in the oxytocin cells, probably as a result of the failure of the abnormal cells to produce vasopressin and its neurophysin and the resultant reduction in hormone packaging. Neurosecretory granules (NSG) 160 nm in diameter were found in the oxytocin perikarya but were absent from the abnormal cell bodies. In addition, a population of small dense granules (SDG) 100 nm in diameter was observed in both types of neurone, in numbers equal to the NSG in oxytocin cells. Injection of a low, non-lethal dose of the axonal transport inhibitor colchicine resulted in a rapid and equal accumulation of both NSG and SDG in oxytocin perikarya and of SDG in the abnormal perikarya after one day. The effects of colchicine were reversed 2-3 days after administration. The SDG, which may contain a co-transmitter or co-hormone substance, are thus produced at a similar rate to NSG, and appear to be transported from the perikarya for subsequent release at the nerve endings. PMID- 4028135 TI - Focal regeneration in the rat myocardium following cold injury. AB - The sequential cytological events in the myocardium of the rat were followed for 3 weeks after cold injury by light and electron microscopy. The traumatized area was initially filled with leukocytes and undifferentiated mononucleated cells and subsequently mainly with fibroblasts surrounded by collagen fibers. However, in the margins of the necrotic area repair processes of damaged myocardial cells and probably also the appearance of newly formed cells were evident. The ultrastructural features of these cells were characterized by clusters of ribosomes, numerous mitochondria that were dispersed in the cytoplasm and formation of junctional complexes and transverse tubular systems. Fibrillogenesis was also clearly evident in these cardiomyocytes. The myofibrillar material was initially dispersed in the cytoplasm and associated with clusters of ribosomes and thereafter with presumptive Z-bands and intercalated discs. The myofibrils became further organized in the shape and orientation of those of mature cells two to three weeks after injury. It is concluded that following cold injury regeneration in the mammalian myocardium takes place but is limited to the perinecrotic area. The process resembles the sequential cytological events which occur in cardiomyocytes during embryonic and postnatal development of the ventricular myocardium. PMID- 4028136 TI - The three-dimensional structure of motor endplates in different fiber types of rat intercostal muscle. A scanning electron-microscopic study. AB - The three-dimensional organization of the motor end plates in the red, white and intermediate striated muscle fibers of the rat intercostal muscle was observed under a field-emission type scanning electron microscope after removal of connective tissue components by HCl hydrolysis. The motor endplate of the white fiber had terminal branches (or axon terminals), which were large, long and thin, and small but numerous nerve swellings (or terminal boutons). The motor endplate of the red fiber had terminal branches, which were small, short and thick, and had large but fewer nerve swellings. The motor endplate of the intermediate fiber was intermediate in size and structure between these two. In detached nerve ending preparations, primary synaptic grooves with slit-like openings of the junctional folds appeared on the surface of the muscle fibers. The primary synaptic grooves were more developed in the white fiber than in the red fiber, and they were intermediate in the intermediate fiber. The numerical ratio of slit like openings was 1:1.8:3.5 in the red, intermediate and white fiber, respectively. The Schwann cells and their processes were observed on the surface of the motor endplate, with the processes covering the upper orifices of the primary synaptic grooves and sealing the terminal branches. The number of Schwann cells was usually three in the white fiber, two in the intermediate fiber and one in the red fiber. PMID- 4028137 TI - The effect of clomiphene citrate on blastocyst development and implantation in the rabbit. AB - The induction of ovulation with clomiphene citrate (CC) in human patients results in a high ovulation rate but achieves a relatively low pregnancy rate. To clarify the possible role of CC in interfering with the normal reproductive physiology and embryology, we have used our rabbit model and transferred 4-day-old blastocysts from untreated donors to CC-treated pseudopregnant recipients and from CC-treated donors to untreated pseudopregnant recipients to study embryonic development and implantation. Each group was further subdivided into two subgroups, one receiving CC before and the other after ovulation. CC was administered subcutaneously in three consecutive doses of 10 mg/kg body weight. Ovulation was induced with pregnant mare serum gonadotropin (PMS) and human chorionic gonadotropin (hCG). The implantation rate of the control group, evaluated on day 8 of pregnancy, reached 62.0%. When recipients were treated with CC before ovulation, implantation rate was reduced to 18.8% (P less than 0.0002), and to 20.0% (P less than 0.003) when CC was administered after ovulation. The implantation rate of blastocysts transferred from donors, treated before ovulation, is 22.2% (P less than 0.0055), however, reached 70.8% when treatment was started after ovulation. All implantations were analysed microscopically and showed normal morphological features. Our results demonstrate a potential multiple effect of CC, first on the endometrium by altering its receptivity for the implanting conceptus, second, on tubal physiology by altering egg transport, and finally on ovum maturation before ovulation interfering with development of blastocysts. These parameters may all result in rapid decrease in establishment of implantations and in turn in very low pregnancy rates. PMID- 4028139 TI - Iodine distribution in the thyroid follicles of the hagfish, Eptatretus burgeri and lamprey, Lampetra japonica: electron-probe X-ray microanalysis. AB - In the thyroid follicles of species of cyclostomes, a hagfish and a lamprey, the distribution of stable iodine was examined by electron-probe X-ray microanalysis. A high concentration of stable iodine, heterogeneously distributed, was observed in the follicular cells of hagfish thyroid follicles. In the lamprey a low concentration of iodine was seen in the follicular lumina. The relative values for stable iodine determined in this way corresponded to values obtained by a chemical analytical method. PMID- 4028138 TI - Histofluorescence and ultrastructural observations of small intensely fluorescent (SIF) cells in the superior sympathetic ganglion of the guinea pig. AB - Amine-containing small intensely fluorescent (SIF) cells are ubiquitous in vertebrate sympathetic ganglia and, in some species, SIF cells have been identified as interneurons. The hypothesis proposed in this study is that SIF cells in superior sympathetic ganglia of the guinea pig function as interneurons, with efferent connections characteristic for the species. Fluorescence (catecholamine) microscopy and 5-hydroxydopamine marker for electron microscopy were used to study SIF cells, their processes and connections in this ganglion. Brightly fluorescent fibers were seen attached to virtually all SIF cells, and were of two types. The first type, single or arranged in cords, interconnected elements of the SIF-cell system; these apparent linkages joined individual SIF cells as well as adjacent clusters. The electron-microscopic evidence for synaptic contacts between SIF cells warrants the claim that integrated action is a presumed function of these elements. The second type of SIF-cell process was generally of greater length. These individual, branching fibers made presumed connections with dendrites of most principal ganglionic neurons. This arrangement suggested by histofluorescence preparations was confirmed by electron microscopy to involve synaptic connections, and the postsynaptic element was shown to be continuous with the perikaryon of the principal ganglionic neuron. Ultrastructural evidence that collections of dense-cored vesicles occur within processes of both principal ganglionic neurons and SIF cells, in proximity to unsheathed portions of plasma membrane, leads to the conclusion that interstitial diffusion of catecholamine from both may occur; the finding of SIF cell processes adjacent to fenestrated blood vessels suggests that catecholamine may also be transported through capillaries. PMID- 4028140 TI - Scanning electron microscopy of macrophages in the tail musculature of the metamorphosing anuran tadpole, Rana japonica. AB - Scanning electron microscopy was used to investigate the morphological changes of the tail musculature of the metamorphosing anuran tadpole, attention being focused on phagocytosis by macrophages. Muscle fibers were stained en bloc with silver and freeze-fractured during dehydration, or torn after drying. Samples were sputter-coated with gold-palladium and observed in both secondary electron- and back-scattered electron modes with a scanning electron microscope. Various cells were identified by the methods of secondary electron- and back-scattered electron images. Some macrophages lying between muscle fibers at prometamorphic stages possessed numerous finger-like projections and well-developed ruffles. During degeneration of muscle fibers macrophages collected in the degenerating region and invaded the space between the disordering myofibrils. In advanced stages the numbers of macrophages clearly increased on or around the degenerating muscle fibers. At the climactic stage fragmented muscles were entrapped and then engulfed by the macrophages. With the completion of phagocytosis, the macrophages became globular with reduction of the ridge-like ruffles. Macrophages may play a role not only in scavenging the fragmented muscle fibers, but also using their long processes in active formation of the fragments. PMID- 4028141 TI - Ultrastructure of enterochromaffin cells and associated neural and vascular elements in the mouse duodenum. AB - Enterochromaffin cells of adult mouse duodenum were studied with light- and electron-microscopical techniques. They were distinguished from other enteroendocrine cells by their pleomorphic, electron-dense secretory granules in the basal cytoplasm. At the apices of enterochromaffin cells, tufts of short microvilli bordered the gut lumen. At their bases, irregular cytoplasmic extensions were either in contact with or passed through the basal lamina. The presence of cytoplasmic extensions in close proximity to fenestrated capillaries and subepithelial nerves suggested an endocrine or paracrine function. Electron micrographs of serial thin sections were used to reconstruct an enterochromaffin cell from the crypt epithelium in three dimensions and to determine its relationship with the underlying neural plexus. Although extensions from the serially sectioned and reconstructed cell and other enterochromaffin cells studied in crypt epithelia protruded through the basal lamina, no synaptic contacts were seen. Evidence of a synaptic contact between a neurite and another type of enteroendocrine cell (possibly an intestinal A cell), suggested a neurocrine role for some of the basally-granulated cells. Possible functions of enterochromaffin cells are discussed in the light of recent literature on the system of enteroendocrine cells, also known as APUD (amine precursor uptake and decarboxylation) cells and/or paraneurons. PMID- 4028142 TI - Scanning electron microscopy of the electric organs of Electrophorus electricus L. II. Organs of Sachs and Hunter. AB - The surfaces of the organs of Sachs and Hunter of Electrophorus electricus L. were examined by scanning electron microscopy. Special attention was directed to morphological details of the electrocyte to provide a better understanding of its anterior and posterior faces. Some aspects of the microanatomy of these organs, which differ markedly from those of the main electric organ, provide new information on the structure as revealed previously by light and transmission electron microscopy. The relief, mainly expressed by papillae, is related to the actual membrane area, which is important for calculations of specific resistance and conductance. Information is also presented on the general organization of the tissue, in particular the distribution of the connective elements and external configuration of synaptic terminals. Shrinkage in preparation of tissue was evaluated and correction made whenever necessary. Correction factors for actual membrane area were calculated for anterior and posterior faces of electrocytes from both organs. PMID- 4028143 TI - Effects of temperature and bright light on myeloid bodies in the retinal pigment epithelium of the newt, Notophthalmus viridescens. AB - Myeloid bodies (MBs) are specialized regions of endoplasmic reticulum which occur in the retinal pigment epithelium of a number of vertebrate species. In the newt, Notophthalmus viridescens, the effects of temperature and brief exposure to bright flashed-light on myeloid bodies have been studied. Morphometric analysis has shown that in animals sampled at 06.30 h, myeloid body sectional area remained unchanged in animals maintained in the cold (1 degree C), compared with control animals at 15 degrees C, whereas phagosome area was significantly increased. At higher temperatures (30 degrees C), myeloid body area was observed to decline from control values, while phagosome area was substantially increased. During the first 2 h of the light phase of a normal (15 degrees C) 12:12 LD lighting cycle, myeloid-body sectional area dropped significantly from values recorded in the latter part of the dark phase. This reduction of MB area at the normal time of "lights-on" was greatly reduced when animals experienced an extended period of darkness. When animals experienced a bright flashed-light at the normal time of "lights-on", followed by a period of extended darkness, reduction in MB area was less pronounced when compared to cycled control animals. These results are discussed in the context of the hypothesis (Yorke and Dickson 1984) that MBs represent a temporary storage site for lipids entering the pigment epithelium after phagocytosis of shed outer segment tips, prior to their permanent storage in lipid droplets.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4028144 TI - Lamellar to tubular conformational changes in the endoplasmic reticulum of the retinal pigment epithelium of the newt, Notophthalmus viridescens. AB - The retinal pigment epithelium (RPE) of the newt (Notophthalmus viridescens) was examined ultrastructurally under both in-vivo and in-vitro conditions. Five distinct conformations of smooth endoplasmic reticulum (SER), two lamellar and three tubular, were observed. The two lamellar conformations included myeloid bodies, which have previously been described (Yorke and Dickson 1984), and fenestrated SER. The latter appeared as layers of flattened or curved cisternae which were penetrated by fenestrations. Fenestrated SER became indistinguishable from the highly branched and convoluted random-tubular SER through the formation of an intermediate configuration ("tubular sheets"). The remaining tubular SER conformations appeared to arise from random-tubular SER through a progressive reduction in branching and a straightening of individual tubules. Fascicular SER was represented by the hexagonal organization of straight, unbranched tubules into bundles (fascicles). Spiral SER consisted of a similar hexagonal arrangement, but the unbranched tubules spiralled about one another. Neighbouring tubules in areas of spiral SER were also joined together by pairs of electron dense bars. Although lamellar (especially myeloid bodies) and random-tubular configurations of the SER were common features in vivo, fascicular and spiral SER were primarily conformations encountered in vitro. Conditions favouring bilayer lipid phases also appear to facilitate the formation of both myeloid bodies and fascicular SER. These conditions included increased duration of incubation, low (less than 20 degrees C) incubation temperatures, and Ca2+-free incubations with EGTA. Random-tubular SEB was most prevalent in media supplemented with fetal calf serum and also after warmer (30 degrees C) incubation temperatures.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4028145 TI - Differentiation of the rat epididymis after withdrawal of androgen. AB - The differentiation capacity of the rat epididymis after depletion of androgen was studied in organ culture and in castrated rats. The differentiation of "narrow cells' in 5- and 10-day-old explants and in 10-day-old castrated rats suggests that: (i) the testicular androgens are not essential for their differentiation, (ii) a differential androgen dependence exists among the epididymal cell types, (iii) the undifferentiated epithelial cells are the precursors of the narrow cells. PMID- 4028146 TI - Formation of autophagosomes in the pinealocytes of the rat and mongolian gerbil (Meriones unguiculatus): a lysosome wrapping mechanism? AB - Autophagosome formation in rat and gerbil pinealocytes is described. It starts with the setting up of a tubular acid phosphatase-rich cisterna which gradually wraps around cytoplasmic areas to be catabolized. In light of obtained findings, it seems that the autophagosome formation in pinealocytes is a type of lysosome wrapping mechanism. PMID- 4028147 TI - [Use of ELISA in detecting antibodies against L. pneumophila serogroup 1 in 195 healthy persons in Tianjin]. PMID- 4028148 TI - [Seroepidemiologic study of viral hepatitis B in a suburb of Beijing]. PMID- 4028149 TI - [Preliminary survey of toxoplasmosis in Zhanjiang region]. PMID- 4028150 TI - [Preliminary study on toxoplasmosis in Tongshan County]. PMID- 4028151 TI - [Epidemiological evaluation of a 20-year program in the control of malaria in Mun hai County Yunan Province]. PMID- 4028152 TI - [Evaluation of the release rate of an enveloped slow-release larvicide and its efficacy in mosquito control]. PMID- 4028153 TI - [Controlled-release tubes containing phoxim in killing larvae of Aedes albopictus]. PMID- 4028154 TI - [Control of house rodents in villages and towns using baiting boxes containing toxic baits]. PMID- 4028155 TI - [A case-control interview study on risk factors of lung cancer in the city of Taiyuan]. PMID- 4028156 TI - [Measurement of error and evaluation of epidemiologic data]. PMID- 4028157 TI - Headache 1985. Proceedings of the Second International Headache Congress. Copenhagen, June 18-21, 1985. Abstracts. PMID- 4028158 TI - Big may not be beautiful, but it is necessary. PMID- 4028159 TI - Expression of the human c-fms proto-oncogene in hematopoietic cells and its deletion in the 5q- syndrome. AB - The c-fms proto-oncogene was shown to be expressed in human bone marrow and in differentiated blood mononuclear cells, suggesting that its gene product plays a role in hematopoietic maturation. The c-fms mRNA was not detected in HL-60 cells, an established promyelocytic line, whereas c-fms expression appeared 48 hr after induction when most cells had differentiated into macrophages. An acquired deletion of chromosome 5 (5q-) in bone marrow cells is associated with abnormalities in blood cell production. The normal 5 and 5q- chromosomes were segregated by construction of cell hybrids between bone marrow and rodent cells. A selective system was used that requires retention of the structural gene for dihydrofolate reductase, located on human chromosome 5. Analysis of DNA from individual hybrid clones revealed that the 5q- deletion had removed the c-fms gene. We postulate that hemizygosity at the c-fms locus leads to abnormalities in hematopoietic maturation. PMID- 4028160 TI - Sequences required for in vitro transcriptional activation of a Drosophila hsp 70 gene. AB - The hsp 70 gene of Drosophila contains three domains to which a heat shock gene specific transcription factor (HSTF) binds. In addition to the previously described 55 bp binding domain proximal to the TAT homology, there are two 25 bp binding sites farther upstream. Footprinting studies with 5' and 3' deletion mutations show two contiguous HSTF binding sites of different intrinsic affinities within the 55 bp binding domain. Determinations made with an agarose acrylamide gel assay suggest that the HSTF possesses a 12.5-fold higher intrinsic affinity for the site closest to the TATA homology than for the more distal site. Binding of HSTF to the distal site thus appears cooperative, requiring occupancy of the first site. Transcription studies in vitro on the 5' deletions with nuclear extracts and reconstitution experiments show that the TATA proximal site alone, is insufficient for maximal transcriptional activation of the hsp 70 gene. PMID- 4028161 TI - Mutants and pseudorevertants of Moloney murine leukemia virus with alterations at the integration site. AB - Soon after infection, retroviruses synthesize a DNA copy of the genomic RNA and insert that DNA into the cellular genome by recombination at inverted repeat sequences at the termini of the viral genome. We have generated mutations that alter one terminus of the genome of Moloney murine leukemia virus (M-MuLV). Some mutations did not prevent integration of the viral DNA even though the very terminal bases were disrupted. Other mutations had dramatic effects on the efficiency of infection; in these cases the formation of preintegrative DNA was normal but the establishment of the productive provirus was prevented. One of these defective mutants gave rise to a pseudorevertant which differed from the wild type but displayed normal infectivity. An unusual number of bases of viral DNA were removed during the integration reaction carried out by this virus. PMID- 4028162 TI - Prothoracic transformation and functional structure of the Ultrabithorax gene of Drosophila. AB - The activity of the Ultrabithorax (Ubx+) gene is necessary for the characteristic development of a particular anatomical domain of the body of Drosophila. Mutant alleles at the abx, bx, bxd, and pbx loci eliminate specific functions of Ubx+ since their phenotype is part of that of Ubx mutants. We have characterized several abx and bx alleles and found that their effect extends to the same anatomical subdomain. This suggests that they inactivate the same genetic subunit within Ultrabithorax. Also, their wild-type activity is required for two distinct functions: postprothorax, acting early in the embryonic period, and bithorax, acting through embryonic and larval periods. Our results suggest that the Ultrabithorax gene contains two genetic subunits and that each subunit may include two separate functions. PMID- 4028163 TI - Developmentally regulated cell surface structures on mouse and human embryonal carcinoma cell lines. AB - Three monoclonal antibodies 5.1.H, 8.7.D and 13.7.A raised against semi-purified Tera 1 membrane fractions recognize distinct onco-foetal antigens which are developmentally regulated on cells such as Tera 2 clone 13 and appear to be restricted in their expression to undifferentiated ectoblastic cells and certain organized cystic structures mimicking the foetal intestine. These antigens, absent from normal adult tissues, differ markedly from glycosidic stage-specific antigens such as 75.12 which, while functioning as embryonal carcinoma differentiation markers, are also expressed on certain adult tissues. No evidence for a role of fucosyltransferases in regulating either 75.12 or SSEA-1 antigen expression on embryonal carcinoma cells or for the presence of lectin-like structures recognizing these antigens on such cells was found. PMID- 4028164 TI - Enhancement of spicule formation and calcium uptake by monoclonal antibodies to fibronectin-binding acid polysaccharide in cultured sea urchin embryonic cells. AB - The effect of monoclonal antibodies to fibronectin-binding acid polysaccharide (anti-FAPS) on differentiation of primary mesenchyme cells and spicule formation was examined in cultured embryonic cells isolated from the sea urchin, Hemicentrotus pulcherrimus. Spicule formation of micromere-derived cells was enhanced by anti-FAPS. The increase of spicule formation correlated with the increase of calcium uptake into micromere-derived cells and spicules. Furthermore, both spicule formation and calcium uptake were inhibited by calcium channel blockers (verapamil, diltiazem and nicardipine) and divalent ions (manganese and cobalt). These results suggest that FAPS, a component of the blastocoelic extracellular matrix surrounding the primary mesenchyme cells, may regulate the level of calcium uptake and spicule formation. PMID- 4028165 TI - The cytotoxic reaction of hemocytes from the freshwater crayfish, Astacus astacus. AB - Crayfish hemocytes displayed cytotoxic capacity towards all tested mammalian tumor and nontumor cell lines. The ratio required for the cytotoxic action of effector cells to target cells was at least 1:1. The lysis of the target cells required a minimum of 1 hr to become detected. After separation and isolation of the hemocyte populations of crayfish, the semigranular and granular cells retained their cytotoxic capacity. These cells contain the prophenoloxidase activating (proPO) system, a complement-like pathway, which in an activated form lyses semigranular cells in vitro, but failed to kill the tested target cells. PMID- 4028166 TI - The role of dendritic cells in the initiation of immune responses to contact sensitizers. I. In vivo exposure to antigen. AB - Twenty-four hours after skin painting mice with picryl chloride (PIC) there was a four- to fivefold increase in the numbers of dendritic cells (DC) isolated from the lymph nodes. These DC initiated primary proliferative and cytotoxic responses when added to cultures of normal syngeneic lymph node cells. The proliferative response was enhanced when the donors of the responding lymph node cells were sensitized with the same antigen. Contact sensitivity developed in syngeneic mice injected into the footpads with 30,000-50,000 DC from lymph nodes of mice painted with picryl chloride 1 day previously. Thus, 1 day after skin painting mice, there were dendritic cells in the draining lymph nodes which were able both to initiate primary stimulation of lymphocytes in vitro and to sensitize recipient mice to give specific delayed hypersensitivity reactions. PMID- 4028167 TI - Rejection of murine ovarian cancer following treatment with regional immunotherapy: correlations with a neutrophil-mediated activation of cytostatic macrophages. AB - Rejection of the murine ovarian teratocarcinoma (MOT) in C3HeB/FeJ mice, following intraperitoneal (ip) treatment with Corynebacterium parvum (C. parvum), is abrogated by injections of silica. We, therefore, investigated whether C. parvum-elicited macrophages affect MOT targets in vitro. Tumor-cytostatic, but not cytolytic, macrophages were detected in normal and tumor-challenged mice treated with C. parvum. The dose responsiveness and kinetics of macrophage activation strongly correlated with tumor rejection. A pyridine extract of C. parvum, possessing greatly diminished tumor rejection properties, was significantly less effective in activating macrophages. Cytostatic macrophage activation and prevention of tumor outgrowth also followed treatment in C3H/HEJ mice, a strain with a known deficiency in cytolytic macrophage function. Peritoneal neutrophils, obtained 6 hr after treatment with C. parvum, were capable of activating cytostatic macrophages when reinjected ip into normal mice. These results indicate a critical role for tumor cytostatic macrophages in this immunotherapy model and suggest their activation is mediated by inflammatory neutrophils. PMID- 4028168 TI - Characterization of the in vitro interaction of PNAhi lymphocytes with the bone marrow and hepatic asialoglycoprotein receptors. AB - We have previously identified an in vivo interaction between circulating PNAhi lymphoid cells and the hepatic asialoglycoprotein receptor, which results in a protracted liver sequestration of these cells. An in vitro frozen section binding assay was developed to study the interaction of PNAhi cells with the receptor in more detail. This assay confirmed that the sequestration of PNAhi lymphoid cells by the liver was mediated by the asialoglycoprotein receptor, as binding was inhibitable by coincubation with galactose, asialoglycoproteins, chelation of divalent cations, or a specific anti-asialoglycoprotein receptor antiserum. This frozen section binding assay was utilized to demonstrate the existence of a bone marrow asialoglycoprotein receptor which was found to be capable of binding to PNAhi lymphocytes or asialoglycoproteins bound to synthetic substrates. We further established that the bone marrow receptor differed both functionally and antigenically from its hepatic analogue. PMID- 4028169 TI - Demonstration of a macrophage migration enhancement factor in the sera of young rabbits. AB - Alveolar macrophages (AM), harvested from the lungs of untreated normal young rabbits (New Zealand White) 14 days to 8 weeks of age, exhibited a state of migration stimulation compared to AM from normal adult rabbits (5 to 6 months of age). Migration of AM from normal adult rabbits (New Zealand White) was stimulated 2.0- to 2.5-fold when incubated with sera from 39- to 46-day-old rabbits compared with sera from normal adult rabbits. Furthermore, 4-day spleen cultures obtained from animals 28 to 59 days of age yielded supernatants that also stimulated the migration of adult AM. The spleen cell culture supernatants from 42- to 49-day-old animals had the greatest activity and stimulated the migration of adult AM 2.5- to 3.2-fold compared to the supernatants from adult normal rabbits. The peak production of migration enhancement factor (MEF) by splenic lymphoid cells coincided with the peak activities found in the sera. It was observed that nonadherent peanut agglutinable lymphoid cells produced MEF. When sera or culture supernatants containing MEF were mixed with MIF-containing adult sera or spleen cell culture supernatants, the respective activities were neutralized. The large migrations of normal neonatal AM were diminished by the addition of MIF-containing sera obtained from BCG-sensitized/challenged rabbits. In contrast, AM from BCG-sensitized rabbits, which exhibited a state of reduced migration, were enhanced by MEF-containing sera from untreated young rabbits. Three peaks of MEF activity were detected in Sephadex G-100 column fractionated sera from 42-day-old rabbits having MWs of approximately (Peak I) 80,000, (Peak II) 43,000, and (Peak III) 8000 to 18,000; most of the activity was found in peaks II and III. Two peaks of MEF activity were detected in Sephadex G-100 column-fractionated spleen cell culture supernatants from 42-day-old rabbits having MWs of approximately (Peak I) 35,000 to 43,000 and (Peak II) 10,000 to 14,000; most of the activity was in peak I which corresponds to peak II of the serum fractionation experiment. Collectively, these data indicate that MEF is a lymphokine that could be important in the modulation of cell-mediated immune effector responses. PMID- 4028170 TI - Evolution of alloantibodies and suppressor cells in allografted mice treated for passive enhancement. AB - The kinetics and quality of the alloimmune reaction were studied in CBA (H-2k) mice treated for passive enhancement of tumor allografts (Sa 1 indigenous of A/J (H-2a or H-2k/d) mice). Serum samples of treated animals were tested for their biological properties relevant to different antibody isotypes in vitro (hemagglutination, complement-dependent cytotoxicity, and anaphylaxis, i.e., mast cell degranulation involving all main Ig isotypes; IgM, IgG2, and IgG1, IgE, respectively) as well as in vivo (allograft enhancement). Spleen cells from these treated animals were examined for their capacity to interfere with the rejection of tumor allografts by adoptive transfers into syngeneic recipients. In vitro, 51Cr release cytolysis assays were performed in order to test their cytolytic and regulatory activities in comparison to rejecting control animals. It has been shown that: grafted mice, pretreated for passive enhancement, kept their grafts longer and synthetized anaphylactic antibodies (mainly IgG1) earlier and at higher titers than normal serum controls, which rejected the same Sa 1 allografts. Mice with enhanced tumors synthetized cytotoxic antibodies (mainly IgG2) later than rejecting controls. Serum samples from treated and control animals, harvested 10 days (early sera) and 30 days (late sera) after grafting, were injected with a "normal dose" (0.2 ml) and a "high" dose (0.4 ml) to new CBA recipients grafted with Sa 1. Early immune sera were only enhancing at high doses when derived from animals previously treated for enhancement (at the low dose both immune sera were enhancing). Late sera, presenting both complement-fixing, cytotoxic (predominantly IgG2), and IgG1 anaphylactic alloantibodies in the two groups, induced enhancement in all cases, but more strongly when derived from the group treated for Sa 1 enhancement. Adoptive transfer of spleen cells from animals treated for passive enhancement were able either to inhibit the accelerated rejection (Day 10) or to promote enhancement of Sa 1 allogeneic cells (Day 30) while similar cells taken (Day 10 and Day 30) from control graft rejecting mice transferred accelerated rejection. Among the transferred T-cell sub-populations, the suppressive effect was mediated by Lyt 2 T cells. In vitro, these spleen cells showed a weaker cytolytic activity than those of allograft rejecting mice. Moreover, they were able to regulate the cytolytic activity of cytotoxic effector cells from specifically immunized CBA mice. PMID- 4028171 TI - Inhibition of macrophage activation by calcium channel blockers and calmodulin antagonists. AB - The biochemical mechanisms by which macrophages become activated to the tumoricidal state are poorly understood. To investigate the role of calcium in this process, the effect of calcium channel blockers and calmodulin antagonists on the acquisition of tumoricidal properties by macrophages activated by a number of different agents was examined. Activation of thioglycollate-stimulated C57BL/6 mouse peritoneal macrophages by macrophage activation factor (MAF) plus LPS, IFN gamma plus LPS or the calcium ionophore, A23187, was inhibited in a dose dependent fashion by the calcium channel blockers nifedipine and verapamil. These agents blocked the influx of 45Ca into macrophages activated by MAF plus LPS. Macrophage activation was also inhibited by chlorpromazine, W-7, and calmidazolium at concentrations known to perturb calmodulin function. The data suggest that activation of macrophages to the tumoricidal state is a calcium dependent process involving the participation of calcium-regulated biochemical reactions whose activities can be modulated by pharmacological agents that frustrate transmembrane calcium fluxes and/or inhibit calmodulin function. PMID- 4028172 TI - Uptake and transport of ferritin in the epithelium of carp (Cyprinus carpio L.) and the possible immunological implications. PMID- 4028173 TI - Embryonic development of the pig: ultrastructure and uptake of macromolecules during early pregnancy. PMID- 4028174 TI - Surface markers of male germ cells in early development of carp (Cyprinus carpio L.) and the blood-testis barrier in fish. A study with monoclonal antibodies and horseradish peroxidase (HRP). PMID- 4028175 TI - Muscarinic receptors in rat nasal glands. PMID- 4028176 TI - Dynamics in immunocytochemical labelling of granules in the gonadotrops of the African catfish Clarias gariepinus, as a function of induced release. PMID- 4028177 TI - Uptake of particulate and soluble antigens in the small intestines of the rat. PMID- 4028178 TI - Uptake of antigens and inert particles by bronchus associated lymphoid tissue (BALT) epithelium in the rat. PMID- 4028179 TI - Endocytosis in adipokinetic hormone (AKH)-producing cells of the migratory locust, Locusta migratoria, in rest and during flight. PMID- 4028180 TI - Rat thymic dendritic cells in culture. PMID- 4028181 TI - Identification of human resident macrophages in continuous ambulatory peritoneal dialysis patients. PMID- 4028182 TI - Steroid aromatase, 2-hydroxylase and COMT activity in gonadotropic cells of the African catfish, Clarias gariepinus. PMID- 4028183 TI - Glucose inhibits cellular ascorbic acid uptake by fibroblasts in vitro. AB - It has been suggested earlier that the local deficiency of ascorbic acid in tissues could be responsible for development of various angiopathies in diabetes. Hyperglycemia is one of the factors which could contribute considerably to the development of local ascorbic acid deficiency. Therefore, the effect of glucose on uptake of L-[1-14C] ascorbic acid by fibroblasts was studied in vitro. The data clearly show that ascorbic acid uptake is inhibited instantly by glucose in a concentration dependent fashion. The results support the contention that local ascorbic acid deficiency in tissues could be a natural consequence of hyperglycemia of whatever cause. The rate of ascorbic acid uptake under various conditions suggests that additional supplements of ascorbic acid might be helpful to individuals in averting deleterious effects of hyperglycemia on tissue ascorbic acid supply. PMID- 4028184 TI - Selective extraction of Chara actin bundles: identification of actin and two coextracting proteins. AB - The sub-cortical actin bundles of the alga Chara corallina can be selectively extracted with a low salt solution except when cytochalasin B is present. Proteins with molecular weights of 160000, 43000 and 37000 share this extraction behaviour. While chemical cleavage of the 43000 band indicates that it is actin, the nature of the other proteins is unknown. Although the 37000 protein resembles tropomyosin in molecular weight it lacks tropomyosin's distinctively large change in electrophoretic mobility in the presence of urea. PMID- 4028185 TI - The effects of two physiological salines, Locke's and van Harreveld's, on the midgut red chromatophores of the freshwater shrimp, Caridina denticulata. AB - It was reported previously that the red chromatophores on the midgut of a freshwater shrimp, Caridina denticulata, are affected by Locke's and van Harreveld's solutions differently, i.e., the pigment disperses in Locke's solution and concentrates with the addition of crude eyestalk extract, but in Harreveld's solution the chromatophores do not change in the saline alone nor do they respond to eyestalk extract. The differences were probably due to the osmotic pressure and Mg ion concentrations of the two solutions not being the same. Harreveld's solution is commonly used as a physiological saline for freshwater crustaceans such as crayfish. Consequently, this solution was employed at first in a previous study (Miyawaki and Tsuruda, 1985). But this solution completely inhibited pigment migration in the chromatophores. But when Locke's solution was subsequently tried, migration of the pigment in the midgut chromatophores occurred. It seemed worthwhile to examine further the effects of both solutions on these chromatophores. The results of this study are presented below. PMID- 4028186 TI - Freeze-fracture replicas of rat ameloblasts reveal unusual membrane domains around gap junctions. AB - Specimens of aldehyde-fixed and glycerol-impregnated tooth germs obtained from 1 2 day old rats were prepared for ultrathin section studies and for freeze fracture, with the purpose of studying the structural organization of membranes of developing ameloblasts. In this report we describe unusual membrane domains which were found surrounding several ameloblast gap junctions. Developing ameloblasts - when examined in ultrathin sections - exhibit gap junctions which appear straight, curved or invaginated. In freeze-fracture replicas, in addition to their typical appearance, several gap junctions were found to be surrounded by a membrane margin which was undulating and devoid of intramembrane particles (IMP's). We believe that these hitherto unreported particle-free membrane margins are associated with the formation of curved or invaginated gap junctions. It is possible that these membrane margins are particle-free because plasma membrane proteins (presumably IMP's) become transiently detached from the cytoskeleton and move laterally. It is therefore likely that these margins are pure lipid domains which are more flexible, thus providing a transient hinge-like mechanism which facilitates the movement required for the formation of the curved or invaginated ameloblast gap junctions. PMID- 4028188 TI - An ultrastructural study of the compensatory myofibrillar adaptation. PMID- 4028187 TI - Increased actin content in cytochalasin D-treated cells is not caused by a selective decrease in actin degradation. PMID- 4028189 TI - Dense line in cisterna of rough-surfaced endoplasmic reticulum of hepatocytes of the rat perfused with saponin solution. AB - The effect of brief perfusion of saponin solution to the membrane of rough surfaced endoplasmic reticulum (r-ER) was observed in hepatocytes at electron microscope level. The liver of rats was perfused with 1% saponin solution in 0.2m phosphate buffer (pH 7.0) for 3 min. then perfused again with 4% glutaraldehyde buffered with 0.1m sodiumcacodylate-HCl at pH 7.4. The most striking alteration of ultrastructure of hepatocytes was the dense intracisternal line of the r-ER. That dense line often had cross striation or "ladder structure". Although its functional significance remains to be cleared, it should reflect the denature of membrane structure of r-ER as one of effects of saponin. PMID- 4028190 TI - Cartilage-derived anti-tumor factor (CATF) inhibits the proliferation of endothelial cells in culture. AB - Previous studies showed that a cartilage-derived anti-tumor factor (CATF), which was extracted from bovine cartilage with 1 M guanidine hydrochloride, inhibited the growth of solid sarcoma 180, but not the growth of ascites tumors of sarcoma 180 [Suzuki, F. et al. Jpn. J. Bone Metab., 2, 231-235 (1984)]. This study showed that CATF inhibited the proliferation and DNA synthesis of endothelial cells isolated from bovine pulmonary artery, but not the proliferations of sarcoma 180, L1210 and L cells. These results suggest that CATF has anti-angiogenic properties, thereby inhibiting the growth of solid tumors. PMID- 4028191 TI - Biosynthesis of laminin and fibronectin by rat satellite cells during myogenesis in vitro. AB - The biosynthesis of fibronectin and laminin was studied in satellite cells cultured from adult rat muscles before (day 4) and after fusion and formation of myotubes (day 14) using (35S) methionine as a tracer. The kinetics of incorporation into immunoprecipitable fibronectin and laminin were recorded at intervals from 1.5 to 24 hours of incubation with the tracer from the cells, the pericellular matrix and the culture medium. The rate of synthesis of fibronectin and laminin expressed as dpm/microgram DNA were constant from the mononucleated cell to the myotube state. Both glycoproteins were detected in the cells and in the pericellular matrix. When the results were expressed as the percentage of incorporation into total protein, major changes could be observed in the early phase of the kinetic studies in the cells and the pericellular matrix. Both showed an increase from the mononucleated myoblast to myotube, suggesting that an increasing fraction of total protein biosynthesis is directed towards these two extracellular matrix glycoproteins. At the same time, there was a decrease in the secretion into the medium of freshly synthesized radiolabeled fibronectin and laminin. Our results confirm the synthesis of varying ratios of both extracellular matrix macromolecules by undifferentiated mononucleated myogenic cells as well as myotubes. PMID- 4028192 TI - Proliferation of human embryonic corneal stromal cells in a serum-free medium. AB - Substantial multiplication of stromal cells from human embryonic corneas has been obtained in a basal medium MCDB 104 supplemented with 25 ng EGF/ml, 10 micrograms insulin/ml, 20 micrograms transferrin/ml, 25 ng MSA/ml, 500 micrograms ovalbumin/ml, 50 micrograms LDL/ml, 50 micrograms HDL/ml and 10(-6) M hydrocortisone. Even though the growth rate appears to be similar to that in 10% serum, the cells cease proliferating at a lower density. PMID- 4028193 TI - Immunocompetent cells in the starfish Asterias rubens. An ultrastructural study. AB - Cells from the axial organ of the starfish Asterias rubens were fractionated into two populations, adherent and non-adherent to nylon wool. In both populations the ultrastructural study revealed the presence of cells resembling the lymphocytes of the vertebrates, as well as phagocytic, peroxidase positive cells. The lymphocyte-like cells in the non-adherent population (average diameter 4 mu) have a high nucleo-cytoplasmatic ratio and are morphologically similar to Th lymphocytes while the adherent cells (average diameter 5.5 mu) are more similar to Bm lymphocytes. These observations are in line with the hypothesis that there exist, in the starfish, a primitive immune system with characteristics resembling those of the immune system of vertebrates. PMID- 4028194 TI - Glycoproteins associated with brain microtubules. PMID- 4028195 TI - Effects of de-efferentation on chick spinal motoneurons: peroxidase-uptake, and activities of acid phosphatase and N-acetyl-B-glucosaminidase. PMID- 4028196 TI - Chromatin organization in Paracentrotus lividus eggs. AB - After purification by buoyant density centrifugation in ethidium bromide - CsCl gradient and electrophoretic fractionation, the DNA fragments isolated from P. lividus egg nuclei incubated with micrococcal nuclease exhibit a typical oligomeric pattern. Analysis of chromatin samples digested to an increasing extent by micrococcal nuclease reveals that the structural organization of egg chromatin is heterogeneous, both in terms of repeat size and degree of sensitivity to nuclease attack. The nucleosomal repeats of P. lividus sperms and embryos up to the mesenchyme blastula stage have also been determined, for comparison. PMID- 4028198 TI - Cell communication compartments in molluscan embryos. AB - Early embryos of Patella vulgata have been injected with Lucifer Yellow. No restriction of dye spread was found. We show that later in the development, the larval trochophore stage present evidence of compartments of cell communication. These dye compartments coincide with different presumptive regions. PMID- 4028197 TI - Response of interphasic nucleoli to hypoxia in root meristems. AB - Hypoxia produces structural changes in interphasic nucleoli of Allium cepa L. root meristems. Following segregation, the fibrillar portion of nucleoli seems to be extruded in masses, accessory bodies, which stay in nucleoplasm. Such bodies apparently leave the fibrillar portion in places which seem to correspond to insertion areas of the nucleolar organizers in nucleoli. Reversal of these changes is rapidly obtained when oxygenation is restored. Accessory bodies differ from prenucleolar bodies since they are compact and homogeneous and they do not display segregation under hypoxia. PMID- 4028199 TI - Dilated cisternae of nuclear envelope and rough endoplasmic reticulum in the proventriculus of Drosophila auraria larvae. AB - In the cells of the middle layer of the proventriculus of Drosophila auraria larvae, the nuclear envelope and the rough endoplasmic reticulum are always found in the form of dilated cisternae. The length of these cisternae can reach 10 mu. There are indications that materials from the outer membrane of the nuclear envelope are directly transported to the Golgi complex of the examined cells. PMID- 4028200 TI - [The effect of VULM 411 on the rhythmogenic center of the myocardium]. PMID- 4028201 TI - [Biological side-effects of potential antitubercular agents. VIII. Antimitotic activity of thiobenzamides substituted on the nitrogen thioamide function group or on the aromatic cycle in position 2]. PMID- 4028202 TI - [Possibilities of preparing coagulatively effective concentrates from human plasma in the transfusion service]. PMID- 4028203 TI - [Documentation of the Society's activity in the development of the Czech Pharmaceutical Society as a contribution to the study of pharmaceutic history]. PMID- 4028204 TI - [The significance of acceleration in the intrapartum cardiotocogram]. PMID- 4028205 TI - [Therapy of fetal hypotrophy]. PMID- 4028206 TI - [Personal experience with the roll-over test]. PMID- 4028207 TI - [Possibilities of detecting extrauterine pregnancy by radioimmunologic determination of chorionic gonadotropins in the blood]. PMID- 4028208 TI - [Use of Sevatest HCG-latex in ambulatory gynecologic practice]. PMID- 4028209 TI - [Serous cystadenoma ovarii permagnum]. PMID- 4028210 TI - [Legal admissibility and the consequences of artificial insemination and inovulation]. PMID- 4028211 TI - [Detection of chlamydia in patients with trachoma]. PMID- 4028212 TI - [Results of a microbiological examination of the conjunctival sac at the Eye Clinic in Brno 1979-1983 in patients with planned intraocular surgery]. PMID- 4028213 TI - [An epidemic of keratoconjunctivitis at the ophthalmic department in Levoca from October to December 1981]. PMID- 4028214 TI - [Changes in the lens after 60Co irradiation]. PMID- 4028216 TI - [Idiopathic inflammatory pseudotumor of the orbit in childhood. Clinical study]. PMID- 4028215 TI - [Gold therapy and the eye]. PMID- 4028217 TI - [Classification of endothelial findings in congenital glaucoma using computer analysis]. PMID- 4028218 TI - [Eye manifestations in oxalosis]. PMID- 4028219 TI - [Recurrent painful ophthalmoplegia (Tolosa-Hunt syndrome)]. PMID- 4028220 TI - [Transient psychogenic concentric narrowing of the visual field]. PMID- 4028221 TI - [Central areolar choroidal dystrophy]. PMID- 4028222 TI - [Computer tomography in laryngeal diseases]. PMID- 4028223 TI - [Personal experience with the surgical treatment of laryngotracheal stenoses]. PMID- 4028224 TI - [Phonation prosthesis]. PMID- 4028225 TI - [Diagnosis of tumors of the statoacoustic nerve]. PMID- 4028226 TI - [Congenital cervical cysts in data from the ORL department]. PMID- 4028227 TI - [The present state and perspectives in phoniatry education and the organization of phoniatric care in Slovakia]. PMID- 4028228 TI - [Stipula 62, a new drainage product manufactured in Czechoslovakia]. PMID- 4028229 TI - [Modification of the valve system on Friedl's respiratory bronchoscopy to a simple non-valved system]. PMID- 4028230 TI - [Adapters for the terminals of light-conducting cables from East Germany permitting the use of these cables with accessories and optical equipment manufactured by Wolf]. PMID- 4028231 TI - [What is undergraduate training in neurology like?]. PMID- 4028232 TI - [The effect of ischemia and recirculation on protein synthesis in the central nervous system]. PMID- 4028233 TI - [New findings on neuroinfections]. PMID- 4028234 TI - [The effect of nootropic substances on fluctuations in vigilance tonus in postinjury pseudoneurasthenia. EEG study]. PMID- 4028235 TI - [Mutual relations between selected interoreflexive (so-called autonomic) and psychologic parameters]. PMID- 4028236 TI - [Electrodiagnosis of the early stages of the Guillain-Barre syndrome]. PMID- 4028237 TI - [Visual evoked potentials. IV. Reversibility of changes during focal cerebral ischemia induced by occlusion of the median cerebral artery in cats]. PMID- 4028238 TI - [Spinal arachnoid cysts]. PMID- 4028239 TI - [Membranoproliferative glomerulonephritis in children]. PMID- 4028240 TI - [The significance of the diagnosis of aorto-pulmonary collaterals in the tetralogy of Fallot]. PMID- 4028241 TI - [Homocystinuria]. PMID- 4028242 TI - [Cystathioninuria]. PMID- 4028243 TI - [2 cases of bronchial carcinoid in children]. PMID- 4028245 TI - [Hair loss in children and adolescents]. PMID- 4028244 TI - [Possibilities of new therapeutic approaches in renal diabetes insipidus]. PMID- 4028246 TI - [The ratio of genetically-conditioned pathologic states in child mortality between the age of 8 days and 1 year]. PMID- 4028247 TI - [Preliminary results of foster care of children at risk who have been transferred from a home for children and infants]. PMID- 4028248 TI - [Late manifestations of congenital pulmonary emphysema]. PMID- 4028250 TI - [Diagnosis of isolated tracheoesophageal fistula--the Coop or Fabian test?]. PMID- 4028249 TI - [The number of gypsy children hospitalized in the pediatric department of the District Health System in Presov]. PMID- 4028251 TI - [Current problems in pediatric nephrology]. PMID- 4028252 TI - [The pediatrician and the family]. PMID- 4028253 TI - [Inhalation aerosol scintigraphy of the lungs in childhood]. PMID- 4028254 TI - [Incidence of manifest diabetes and disorders of glucose tolerance in the family and siblings of children with diabetes mellitus type I]. PMID- 4028255 TI - [Immunologic reactivity of children with idiopathic nephrotic syndrome]. PMID- 4028256 TI - [Treatment of heart failure in children]. PMID- 4028257 TI - [Basis of rational nutrition of infants at the present time]. PMID- 4028258 TI - [The effect of the use of saunas on morbidity due to respiratory diseases in children attending nurseries]. PMID- 4028259 TI - [Defects in the structure of dental tissue in children in Prague]. PMID- 4028260 TI - [How can the child psychiatrist contribute to the pediatrician's care of the child?]. PMID- 4028261 TI - [The history of medicine and health care in Czechoslovakia and its importance in the development of social medicine and the organization of health care]. PMID- 4028262 TI - [Legal regulations of the citizen-health worker relationship. I]. PMID- 4028263 TI - [Medico-legal problems in ambulatory care]. PMID- 4028264 TI - [Use of coefficients of economic requirements in ambulatory care and in hospitals]. PMID- 4028265 TI - [Drug requirements from the the viewpoint of the age structure and sex of a population in a medical region]. PMID- 4028266 TI - [Obesity as a risk factor in hypertension]. PMID- 4028267 TI - [Personal experience with a computerized data base of hospitalized patient records]. PMID- 4028268 TI - [The present and future of emergency surgery]. PMID- 4028269 TI - [Scientific medical information, health education and history in research conducted under the 7th 5-year-plan]. PMID- 4028270 TI - [Double-contrast examination of the stomach in various work environments]. PMID- 4028271 TI - [Radiologic differentiation of proctocolitis from regional (Crohn's) colitis]. PMID- 4028272 TI - [Gastroduodenal obstruction by gallstones (Bouveret's syndrome]. PMID- 4028273 TI - [Possibilities of percutaneous transhepatic cholangiography in the diagnosis and therapy of peracute cholangitis]. PMID- 4028274 TI - [Difficulties in the diagnosis of carcinoid of the small intestine (an error in surgical exploration)]. PMID- 4028275 TI - [Initial experience with B-scan echoencephalography in neurosurgical practice]. PMID- 4028276 TI - [Infectious osseous complications in patients on chronic hemodialysis therapy]. PMID- 4028277 TI - [Incomplete double aortic arch and esophageal reflux disease after type II gastric resection]. PMID- 4028279 TI - [Personal experience with a lymphography kit made in Yugoslavia (TIK Kobarid)]. PMID- 4028278 TI - [Insertion of 2 catheters into a vein using a single puncture]. PMID- 4028280 TI - Resistance to beta-lactam antibacterial agents in hospitals. AB - In recent years, due to the frequent use of antimicrobial agents, strains resistant to antibiotics have been seen with increasing frequency among hospital isolates. We have compared the susceptibility to different beta-lactam drugs of Pseudomonas spp. and Staphylococcus aureus strains, isolated during a 10-yr period (1974-1984) from pathological specimens of different units of Spedali Civili of Brescia Medical School. We have also analyzed the plasmid DNA profile of representative Staphylococcus aureus strains isolated in 1984. PMID- 4028282 TI - Double-blind randomized comparative trial: ornidazole (Tiberal) versus tinidazole (Fasigin) for the treatment of non-specific vaginitis. AB - In a double-blind, randomized trial 60 patients with demonstrated bacteriological and clinical non-specific vaginitis were treated with tinidazole versus ornidazole. Thirty patients received tinidazole 2 g daily taken orally in two separate doses for two consecutive days. Twenty-three patients (76%) were cured, 3 patients (10%) relapsed and 4 patients were therapeutic failures. Thirty patients received ornidazole with the same regimen. Twenty-eight patients (93%) were cured, 1 patient (3.3%) relapsed and 1 patient had intolerance to the medication. PMID- 4028281 TI - Assessing modifications of the intestinal bacterial flora in patients on long term oral treatment with bacampicillin or amoxicillin: a random study. AB - The authors conducted a randomized trial on 16 patients to evaluate intestinal aerobic microfloral changes after prolonged oral treatment with bacampicillin (b.) (16 g/die) or amoxicillin (a.) (2 g/die). The analysis showed a quantitative reduction of isolates in 6 patients: 2 patients were treated with b. while 4 with a. (Odd ratio, O.R. = 3). Mean values of CFU presented as well a more evident reduction in a.-treated patients. From the qualitative point of view, bacteria modifications occurred in one patient treated with b. and 3 with a, (O.R. = 4.2). Bacterial changes, although not statistically significant, were thus greater in patients treated with a. than b. PMID- 4028283 TI - A multicenter, randomized parallel double-blind study comparing three antibiotics, cephemic-cofosfolactamine, fosfomycin and cephalexin, in the treatment of systemic infections. AB - In the present multicenter, randomized and double-blind study, performed on 127 hospitalized patients, we compared the effects of three antibiotics (cephemic cofosfolactamine, cephalexin and fosfomycin) in the treatment of acute or recurrent systemic infections. Results show that the percentage of recoveries of clinical symptoms and of bacterial eradications were significantly higher, and associated with a lower rate of side effects in the patients treated by cephemic cofosfolactamine than in those treated by cephalexin or fosfomycin. PMID- 4028284 TI - Monoclonal antibodies and the human breast. AB - This resume has focussed attention upon some aspects of the clinical and pathological utility of breast-directed antibodies. Such related probes may also be of value in novel aspects of therapy for this group of disorders and as agents for radio-immunolocalisation. PMID- 4028285 TI - Effect of beta-lactam antibiotics at subinhibitory concentrations on the phagocytosis of Staphylococcus aureus by the perfused rat liver. AB - We evaluated whether the exposure of Staphylococcus aureus to a subinhibitory concentration of penicillin and cefamandole could modify its susceptibility to rat serum factors and to the phagocytic activity of the isolated and perfused rat liver. Control or sub-MIC treated bacteria were added to the circulating medium which contained homologous serum, and the disappearance of bacteria from the perfusate and their recovery in the liver was determined during the 10 min experimental time. Sub-MIC treated bacteria were more susceptible to the bactericidal activity of serum present in the perfusate. However, the clearance rate of bacteria by the liver was decreased for penicillin-treated organisms and unchanged for cefamandole-treated bacteria. The data suggest that beta-lactam antibiotics at sub-MIC levels may modify S. aureus susceptibility to host defense mechanisms. PMID- 4028287 TI - Peroxidase-catalyzed benzidine binding to DNA and other macromolecules. AB - [14C]Benzidine is rapidly oxidized by a peroxidase/H2O2 system to products which bind irreversibly to DNA. The presence of exogenous DNA also prevented benzidine polymerization to 'benzidine brown' and azobenzidine. Two molar equivalents of H2O2 were required to oxidize the benzidine and achieve maximal DNA binding. Furthermore, 95% of the benzidine was trapped and 36 nmol benzidine was bound per mg DNA. Polyriboguanylic acid was as effective as DNA in binding benzidine, but polyriboadenylic acid, polyribouridylic acid and polyribocytidylic acid were much less effective. Binding of [14C]benzidine correlated well with the absorbance at 295 nm and 390 nm of the modified DNA or various synthetic homopolymers of ribonucleotides isolated from the reaction mixture. The peroxidase/H2O2 system also catalyzed the binding of dichlorobenzidine, o-tolidine and o-dianisidine to DNA but 3,5,3',5'-tetramethylbenzidine, a non-carcinogen, did not bind. The binding could be prevented by various biological hydrogen donors, thiols, or phenolic antioxidants. The mechanisms for DNA protection were investigated; the oxidized benzidine species involved in binding can be reduced with ascorbate, NADPH, or thiols, and trapped by thiols or phenolic antioxidants to form conjugates or adducts. PMID- 4028286 TI - Spin state control of cytochrome P-450 reduction and catalytic activity in a reconstituted P-450 LM2 system as induced by a series of benzphetamine analogues. AB - Reconstituted liposomal cytochrome P-450 LM2 was reacted with a series of benzphetamine analogues as substrates. Based on the thermodynamical model of Ristau et al. (Biochim. Biophys. Acta, 536 (1978) 226-234) the free enthalpy of substrate binding to the high spin form of the enzyme was shown to correlate with the total high spin content of the respective enzyme substrate complex. Reduction and substrate N-demethylation rates as well have been evidenced to linearly correlate with the substrate-induced spin shift delta alpha and moreover with the spin content alpha. The data obtained provide further experimental support for the spin state regulation of the reduction and conversion rate of cytochrome P 450 LM2. PMID- 4028288 TI - Investigation of absorption, metabolism kinetics and DNA-binding of intratracheally administered benzo[a]pyrene in the isolated, perfused rat lung: a comparative study between microcrystalline and particulate adsorbed benzo[a]pyrene. AB - Benzo[a]pyrene (B[a]P) adsorbed onto urban air particles (UAP) or in microcrystalline form (MCr) was administered intratracheally to the isolated perfused lung in doses of 100 and 1.5 micrograms. The appearance rate constant calculated for B[a]P release to the perfusate buffer was significantly lower for B[a]P administered adsorbed onto UAP (0.007 +/- 0.002 min-1) compared to the microcrystalline preparation (0.051 +/- 0.030 min-1). A classical two compartmental model fitted well to the elimination of B[a]P from the perfusate buffer, after administration in solution to the buffer reservoir; C = 24 e-0.05t + 14 e-0.01t (pmol/ml). The concentration of polar metabolites in the perfusion buffer, at the end of experiments was approx. 9-fold higher for lungs administered the microcrystalline preparation compared to UAP at 1.5 microgram doses. At the 100 microgram dose level, the difference between preparations was only 2-fold, the data indicating that enzyme saturation might be important at the high dose level. With regard to the metabolite pattern, adsorption of B[a]P onto urban air particles caused a relative increase in the formation of B[a]P-9,10 dihydrodiol, whereas the relative formation rate for phenols was decreased. The absolute levels of B[a]P metabolites covalently bound to DNA was significantly higher in lungs given the MCr preparation compared to the UAP. When calculated as the amount metabolites bound, in relation to the total amount polar metabolites at the end of perfusion, however, the UAP preparation was significantly more efficient to enhance the production of DNA binding metabolites; 2.62 +/- 0.59 X 10(-5) vs. 1.33 +/- 0.21 X 10(-5) (pmol covalently DNA-bound metabolites/mg DNA/pmol metabolites formed). The results indicate that urban air particles may exert a cocarcinogenic effect with polynuclear aromatic hydrocarbons by increasing the pulmonary residence time for the carcinogenic hydrocarbon and/or alter the metabolite pattern in a way that enhances the covalent binding of metabolites to DNA. PMID- 4028290 TI - Trialkyl phosphorothioates and glutathione S-transferases. AB - Using a rat liver cytosol source of enzyme trialkyl phosphorothioates have been shown to be substrates of glutathione S-transferases. Using OSS-trimethyl phosphorodithioate (OSS-Me(O] and OOS-trimethyl phosphorothioate (OOS-Me(O] the methyl transferred to the sulphydryl of glutathione is that attached to phosphorus via an oxygen atom. Fractionation of liver cytosol has shown that although the bulk activity is due to the three isozymes (1-1; 3-4; 1.2), OSS Me(O) is a general substrate for glutathione S-transferases. The specific activity is low compared with the substrates 1-chloro-2,4-dinitrobenzene and 1,2 dichloro-4-nitrobenzene. PMID- 4028289 TI - Comparative studies of the metabolic activation of chrysene in rodent and human skin. AB - Metabolism and activation of chrysene was examined in mouse, rat and human skin using a short-term organ culture technique. Mouse skin released larger quantities of free dihydrodiols into the culture medium than either rat or human skin and greater quantities of chrysene metabolites became covalently bound to the DNA of mouse skin. The stereochemistry of the chrysene-1,2-diol that was formed by each skin type was examined using high-performance liquid chromatography (HPLC) with a chiral stationary phase to resolve the enantiomers. It was found that in each case the (-)-enantiomer predominated. When hydrolysates of DNA extracted from rodent or human skin that had been treated with 3H-labelled chrysene were chromatographed on Sephadex LH-20 columns, the elution profiles of the hydrocarbon-DNA adducts were found to vary between the species studied. Further examination using HPLC showed that some of the adducts formed in skin had the chromatographic characteristics of adducts formed when the anti-isomer of the 'bay-region' diol-epoxide of chrysene (r-1,t-2-dihydroxy-t-3,4-oxy-1,2,3,4 tetrahydrochrysene) reacted with DNA and that others had the characteristics of triol-epoxide adducts. PMID- 4028291 TI - Synthetic studies on platelet-activating factor (PAF). PMID- 4028292 TI - Stereochemistry of hydrogenation of (-)-dehydrogriseofulvin to (+)-griseofulvin with a cell-free system of Streptomyces cinereocrocatus. PMID- 4028293 TI - Synthesis and pharmacological evaluation of piperidine derivatives with various heterocyclic rings at the 4-position. PMID- 4028294 TI - Synthesis of 1- and 3-(1-substituted 4-piperidinyl)-1,2,3,4-tetrahydro-2 oxoquinazolines as potential antihypertensive agents. PMID- 4028295 TI - Spiropiperidines. I. Synthesis of 1'-substituted spiro[4H-3,1-benzoxazine-4,4' piperidin]-2(1H)-one derivatives and evaluation of their antihypertensive activity. PMID- 4028297 TI - Specificity of antisera raised against estradiol 12-bovine serum albumin conjugates. PMID- 4028296 TI - Studies on 2-oxoquinoline derivatives as blood platelet aggregation inhibitors, IV. Synthesis and biological activity of the metabolites of 6-[4-(1-cyclohexyl-1H 5-tetrazolyl)butoxy]-2-oxo-1,2,3,4- tetrahydroquinoline (OPC-13013). PMID- 4028298 TI - High-performance liquid chromatographic determination of 3-methylcytosine in deoxyribonucleic acid treated with carcinogenic methylating agents in vitro and in vivo. PMID- 4028299 TI - Salivary excretion of 5-fluorouracil. I. Fluctuation of the saliva/plasma concentration ratio and salivary clearance in beagle dogs following bolus intravenous administration. PMID- 4028300 TI - Preparation and in vitro degradation properties of polylactide microcapsules. PMID- 4028302 TI - Quantitative structure-in vivo half-life relationships of perfluorochemicals for use as oxygen transporters. PMID- 4028301 TI - 2,2'-Dithiodibenzamides as inhibitors of blood platelet aggregation. PMID- 4028303 TI - Controlled release of pilocarpine hydrochloride from ethylene-vinyl alcohol copolymer matrices. PMID- 4028304 TI - Fluorimetric assay for hydrolytic activity of cholesterol esterase in rat tissues. PMID- 4028305 TI - Effect of simultaneous administration of drugs on absorption and excretion. XIX. Binding of acetohexamide and its major metabolite, (-)-hydroxyhexamide, to human serum albumin. PMID- 4028306 TI - Laser photoacoustic microscopy for the determination of dye on a solid biopolymer. PMID- 4028307 TI - [A new Salmonella serotype isolated in Greece: Salmonella phaliron = 8:z:e,n,z15]. AB - A new Salmonella serotype of sub-genus I, Salmonella phaliron, 8:z:e,n,z15, has been isolated in Greece from sea water polluted from the water of the small river Kifissos. PMID- 4028308 TI - [Crimean-Congo hemorrhagic fever in Africa. Apropos of a case with hemorrhagic manifestations in Mauritania]. AB - The authors report a case of CCHF observed in a patient living in South Mauritania. This is the first case of an haemorrhagic syndrome due to the CCHF virus in West Africa. Data concerning this disease in Africa are brought up to date. PMID- 4028309 TI - [First case of subcutaneous phycomycosis seen in Gabon and treated successfully with ketoconazole]. AB - First observation of subcutaneous phycomycosis observed in Gabon. Diagnosis was made by histological study. Biopsy permitted isolation of B. haptosporus. Sensitivity in vitro against ketoconazole was 1 microgram/ml. The patient cured with 33 g of ketoconazole in 84 days. PMID- 4028310 TI - [Human hypodermyiasis in France in 1984: 266 cases recorded to date. Distribution according to known geographic origin]. AB - The authors, after collecting all human hypodermosis cases in France they know to this day, to the number of 266 (cases in the literature, and unpublished, diagnosed or by them, in the great majority, or by others), make the situation, at the beginning of 1984, of this parasitosis and do comments on the evolution in time of the number of cases according to the geographical regions in France. PMID- 4028311 TI - [2 cases of hydatidosis in the Republic of Niger]. AB - Two cases of hydatidosis have been observed at the hospital of Niamey, one involving the tibia and the other one the liver and the spleen. For unknown epidemiological factors, this helminthiasis is rare in man in western Africa. PMID- 4028312 TI - [Toxoplasmosis in the Central African Republic: first survey]. AB - For this purpose, toxoplasma antibodies were determined by latex agglutination test. Two kinds of human sera were examined: people in "good health" from North of Centrafrican Republic and patients from Bangui. In North, 40% of sera gave positive results and young girls from 1 to 14 years old seem to become positive earlier than young boys. At Bangui, 81% of sera from pregnant women coming from Medical Service was positive; all from 8 patients with ocular affections was positive and only 5 on 10 with adenopathy. PMID- 4028313 TI - [Becoming sedentary, acculturation and infectious diseases: socio-ecological problems of the Bayaka Pygmies]. AB - The falling of tropical rain forests in Equatorial Africa, and the subsequent penetration of Bantu hoe farmers into the former jungle regions are depriving the Pygmies of the basis for their traditional way of life as roaming hunters and gatherers. Most of the former roaming groups now live in permanent settlements near Bantu villages. But becoming sedentary and adapting to the habits of the Bantu have had catastrophic results for the Pygmies: today, this people suffers to a great extent from infectious diseases and animal parasites, which were once almost unknown among them. In particular, Yaws, a skin disease which is widespread in Africa affects whole tribes. With the loss of their cultural identity their social structure also collapses: formerly free Pygmies get employed as cheap labour on coffee plantations. PMID- 4028314 TI - [Nutrition studies in the mid valley of Senegal. 2. Nutritional health of the population and its trends]. AB - A nutritional survey performed in the Senegal mid valley in 1983 including 610 individuals shows that mild to moderate protein-energy malnutrition, specific deficiencies and anemia are still present. In addition new health hazards such as overweight and perhaps high blood pressure, raise and may burden public health welfare in that area. PMID- 4028315 TI - [Osteonecrosis of the femur head caused by sickle cell anemia in Benin. Epidemiologic and radiologic aspects]. AB - The author reports 19 aseptic necrosis of the femoral head, due to sickle cell anemia, collected in 14 black people native from Benin. Sickle cell anemia is the most frequent etiology of osteonecrosis there. They are generally observed between 10 and 30 years of age. A systematic and complete study of the radiological signs has been carried out. The peculiar severity of the disease in black Africa is related to the chronicity of the sickling disorder, the delay brought to the diagnostic, the lack in therapeutic media. PMID- 4028316 TI - [The Great Rift Valley. Parasitological results]. AB - East Africa is separated from the continent by the Great Rift Valley which was created at the end of the secondary era limiting then the East Africa under continent with peculiar fauna and flora features. A several million years long isolation, during the tertiary era, seems to explain that a certain number of protozoan and helminthic diseases present peculiar clinical, epidemiological, therapeutical and parasitological features. The occurrence of those peculiar strains tends to indicate that in this region, for example, the resistance of P. falciparum to amino-4-quinolines is a regional feature which should not largely expand to the rest of the African continent. PMID- 4028317 TI - [Ecology of tick-borne arboviruses in the Central African Republic]. AB - Ticks have been collected on cattle skins for seven consecutive years in Bangui, Berberati, Bangassou and Bouar. 150 strains of arboviruses have been isolated from the four following species: Amblyomma variegatum: Dugbe, Jos, Thogoto, Crimean-Congo Hemorragic Fever (CCHF), Yellow Fever, Bhanja and Petevo; Boophilus annulatus: Dugbe, Jos and Thogoto; B. decoloratus: Dugbe, Jos, Thogoto and CCHF; Hyalomma nitidum: CCHF. Dugbe (112 isolated strains), Jos (19 isolates) and Thogoto (11 isolates) viruses represent more than 95% of all the strains. Dugbe virus was isolated mostly during the first half of the rainy season. Jos virus shows a maximum rate of infection during the dry season (february) and a second peak in october (2nd half of the rainy season). Most of the strains of Thogoto virus have been isolated during the dry season. These seasonal variations of infection rates follow the seasonal variation of vector population densities. Thus preimagines and imagines of A. variegatum, the main vector of the Dugbe virus in C. A. R. show peaks of abundance respectively during the dry season and during the first half of the rainy season. Adults of Boophilus show maximum densities from december to february (dry season) when the greater number of Jos and Thogoto viruses are isolated. CCHF virus ecology needs more studies in Central African Republic. The importance of ticks in the wild cycle of Yellow Fever virus is not yet understood. Bhanja virus has been isolated only one time in C. A. R. Petevo is a lately described virus which belongs to a group thus far unknown in Africa (Palyam gr.). PMID- 4028318 TI - [Endemic pulmonary paragonimiasis in Lower Mundani (Fontem district of southwest Cameroon). Results of treatment with praziquantel]. AB - During a survey on pulmonary paragonimiasis in three villages of Lower Mundani (Cameroon), 35 patients excreting Paragonimus eggs were detected. They were treated with 75 mg/kg per day of praziquantel, administrated in three doses, at 4 to 6 hours intervals, for three days. A three months follow-up, 97.1% of the patients were cured. PMID- 4028319 TI - Clinical manifestations of female trichomoniasis and comparison of direct microscopy and culture media in its diagnosis. AB - A group of 125 women attending a gynecologic clinic was studied to assess the value of four culture media, wet smear and Papanicolaou stained smears and also to re-evaluate the clinical picture in the diagnosis of trichomoniasis. There was no significant difference between the results of 4 different culture media but significant difference was obtained from fresh wet vaginal smears and culture media on the one hand and with Papanicolaou stained smears on the other hand. During the survey, cultures were examined daily for five days, and the Oxoid no. 2 medium gave a majority of positive results and diphasic eggs, CM161 Oxoid, 5447 Merck media were in turn having positive results after 3 days incubation at 36 degrees C. R27, egg, CM161 and 5447 culture techniques and Papanicolaou stained smears, identified T. vaginalis in 37 (29.6%), 33 (26.4%), 30 (24%), 28 (22.4%) and 15 (12%) patients respectively, while the wet mount was positive in 22 (17.6%) patients. R27 culture technique identified T. vaginalis in 37 women, and wet mount was positive in 22 patients (P greater than 0.001). In no case was the vaginal wet mount preparation positive for T. vaginalis and the culture negative. Egg medium detected T. vaginalis in 33 women, in comparison with wet mount positive 22 (P greater than 0.01). Vaginal discharge was described by 72% of the 125 patients, but only 19 (51.4%) Trichomonas vaginalis were detected. Dysuria was present in 73 (58.4%) cases but only 21 (16.8%) were suffering from trichomoniasis. Physical examination revealed no vaginal discharge in 18 (48.6%) of the women, 12 (22.4%) cases had frothy leukorrhea in women with trichomoniasis. PMID- 4028320 TI - [Fertility in Gabon (Haut Obooue). Retrospective study in Okondja and Franceville. Obstetrical activity at the maternity hospital in Franceville during the first trimester of 1981]. AB - This is a report of 2 studies led in Gabon (Haut Ogooue) in 1981: investigation of retrospective fecondity in 2 groups of women (in Franceville and Okondja). The mean number of pregnancies per women (3.8 and 4.3) and the mean descent are close to official reports. This investigation reveals that there is a high neonatal mortality rate, which is likely to have an effect on hypofecondity among women of this area, even more for the older ones; activity of the "Maternite Provinciale de Franceville" during the first semester 1981. PMID- 4028321 TI - [New data on the fleas (Insecta, Siphonaptera) of Algeria]. AB - 28 species or subspecies are noted; 6 are new for this country [Echidnophaga gallinacea (Westwood, 1875), Xenopsylla blanci Smit, 1957?, Ischnopsyllus intermedius (Rothschild, 1898), I. octactenus (Kolenati, 1856), Nycteridopsylla ancyluris Jordan, 1942 and N. pentactena (Kolenati, 1856)]. A new Caenopsylla is described in another paper. PMID- 4028322 TI - [Hemoglobin C in a hospital milieu in Bamako (Mali)]. AB - An hospital survey, performed in Bamako (Mali, West Africa) showed 7.5% haemoglobin AC, 0.4% haemoglobin CC, 1.6% haemoglobin SC and 0.2% haemoglobin CA (haemoglobin C-beta+thalassaemia). Haemoglobin C was mostly prevalent among Bobo, Mossi, Senoufo, Minianka and Dogon coming from the Southern border of Mali. Haemoglobin SC and to a lesser extent haemoglobins CC and CA often induce haemolysis and vasoocclusion. Microcytosis is common, even in the absence of anaemia. PMID- 4028324 TI - DNA ligase activities during hepatocarcinogenesis induced by N-2 acetylaminofluorene. AB - A progressive accumulation of DNA breaks has been reported to occur in nuclear DNA obtained from putative premalignant hepatic lesions induced by carcinogens. To determine if this alteration resulted from a defect in the level of, or functional activity of DNA ligases, we compared these enzymes in normal rat liver, 24-h regenerating liver, and hepatic nodules at intervals after cessation of N-2-acetylaminofluorene (AAF) treatment. Nuclear extracts of hepatocytes were separated into soluble and chromatin fractions, and multiple forms of DNA ligase activity were obtained by AcA34 gel filtration chromatography. In activities of the two largest species, DNA ligase Ia (480 kd) and DNA ligase Ib (240 kd), were present exclusively in soluble, nuclear fractions and were increased 4-fold and 2 fold, respectively, in 24-h regenerating livers. In AAF-induced nodules, these species were increased 3-fold and 1.5-fold, respectively, above those of normal rat liver, somewhat higher than predicted from the rate of cell division. In all of the test tissues, these ligase species demonstrated identical sensitivity to inhibition with 0.1 M NaCl or heating at 50 degrees C. DNA ligase II (80 kd) was found in both soluble nuclear fractions and chromatin at approximately identical levels in all tissues tested. Ligase II from all tissues also demonstrated identical responses to salt and heat. These data support the concept that DNA ligases Ia and Ib are related to DNA replication and suggest that ligase II may be a repair enzyme. The failure to detect significant alterations from expected values in the hepatic nodules and the lack of alteration in sensitivity to salt and heat indicate that the accumulation of DNA damage (presumably breaks) previously observed in carcinogen-induced altered hepatocytes is not due to an alteration in the level or the biochemical properties of DNA ligase. PMID- 4028323 TI - Tissue-specific DNA adduct formation in mice treated with the environmental carcinogen, 7H-dibenzo[c,g]carbazole. AB - Covalent adduction of DNA by chemical agents is commonly thought to be an essential part of the initiation of chemical carcinogenesis. Until recently, assays of DNA damage by covalent binding of chemicals have been restricted mostly to substances that are available in radiolabeled form, which excludes many environmental compounds with carcinogenic potential. In this paper, the binding of non-radioactive 7H-dibenzo[c,g]carbazole (DBC), a known environmental carcinogen, to DNA in female CD-1 mice after s.c. injection of 44 mumol/kg of the compound has been investigated using a 32P-postlabeling assay. DBC showed strong hepatic specificity with a mean total level of 107 adducts per 10(7) nucleotides at 24 h, while much lower levels of binding were seen in kidney, lung, spleen, skin and brain with 4.3, 2.1, 1.3, 0.4 and 0.04 adducts, respectively, per 10(7) nucleotides. Proportions of individual DBC adducts also varied considerably between tissues. The degree of hepatic preference displayed by DBC is not seen with other polycyclic aromatic carcinogens such as benzo[a]pyrene and 2 acetylaminofluorene. The DNA-binding data, together with other hepatotoxic effects of the compound, may be causally related to the known hepatocarcinogenicity of DBC. PMID- 4028325 TI - Indirect induction of a clastogenic effect in epidermal cells by a tumor promoter. AB - The mechanisms by which tumor promoters exert their effects on target tissues are not clearly understood. Recent studies have demonstrated that phorbol ester tumor promoters induce an oxidative burst in phagocytes and DNA single-strand breaks (SSB) in leukocytes. The purpose of the research presented here was to investigate the clastogenic effects of tumor promoters in the target cell population, primary mouse epidermal cells co-incubated with leukocytes. Using the alkaline elution assay to detect DNA SSB, it was demonstrated that tumor promoters induce DNA SSB in primary mouse epidermal cells incubated in the presence of leukocytes. By increasing the ratio of leukocytes to epidermal cells from 1:2 to 10:1, in the presence of 1.6 X 10(-6) M 12-O-tetradecanoylphorbol-13 acetate (TPA), a ratio dependent increase in DNA SSB was observed (from 9 X 10( 2) to 121 DNA SSB per 10(6) nucleotides). A dose response in DNA SSB was seen with TPA over a concentration range of 4 X 10(-9)-1.6 X 10(-6) M. Mezerein, a second stage tumor promoter, induced similar levels of DNA SSB to that of TPA. 4 O-Methyl TPA, a first stage tumor promoter, induced significantly fewer DNA SSB than either TAP or mezerein at similar concentrations. The induction of DNA SSB in epidermal cells treated with TPA and co-incubated with leukocytes was inhibited by catalase but not superoxide dismutase. These data indicate that tumor promoters can act indirectly on target epidermal cells by stimulating the release of a clastogenic factor from leukocytes through a mechanism involving H2O2. PMID- 4028326 TI - Viscometric detection of liver DNA fragmentation in rats treated with ten aromatic amines. Discrepancies with results provided by the alkaline elution technique. AB - A new viscometric technique, capable of detecting DNA strand breaks and alkali labile sites by monitoring time-dependent changes of DNA reduced viscosity, has been used to evaluate DNA fragmentation in liver of rats treated with single i.p. doses of ten aromatic amines. Persistent and dose-dependent changes of DNA viscometric parameters, which are considered indicative of DNA fragmentation, were produced by six hepatocarcinogenic aromatic amines: 2-naphthylamine, benzidine, 2,4-diaminotoluene, auramine O, 4-aminoazobenzene, and 4 dimethylaminoazobenzene. In contrast, changes of liver DNA viscometric parameters were minimal and transient or practically absent in rats treated with aniline, 1 naphthylamine, 4,4'-oxydianiline and 2,4-diaminoanisole, all of which are devoid of hepatocarcinogenic activity. The comparison with data previously obtained with the alkaline elution technique demonstrates that the two methods can give different results, and that viscometrically-detected DNA damage is better correlated with carcinogenic activity than DNA damage detected by alkaline elution. PMID- 4028327 TI - Monoclonal antibodies to 1-aminopyrene-DNA. AB - Monoclonal antibodies were obtained after fusion of mouse P3X63-AG.8.653 myeloma cells with spleen cells isolated from BALB/cCr mice immunized with denatured DNA modified by 1-nitrosopyrene reduced with sodium ascorbate (AP-d-DNA) and complexed electrostatically to methylated bovine serum albumin. Ten stable hybridoma lines have been isolated and characterized by enzyme-linked immunosorbent assay (ELISA). They all recognize 1-aminopyrene (1-AP)-modified DNA, but not free 1-nitropyrene or 1-aminopyrene. Antibody 11H2 is the most specific for AP-DNA showing no cross-reactivity with unmodified native DNA. It also recognizes 8-nitro-1-AP and 6-nitro-1-AP modified DNA. There was some low cross-reactivity with DNA modified by a benzo[a]pyrene diol epoxide and N-acetoxy N-2-acetylaminofluorene. Competitive ELISA with antibody 11H2 reliably detected AP-DNA adducts formed when 1-nitropyrene was incubated with Salmonella typhimurium TA1538. By immunological methods, AP-DNA adducts were shown to be unstable to heat denaturation. This suggests that specific monoclonal antibodies to carcinogen-DNA adducts will be useful not only for detecting and quantitating carcinogen-DNA damage but also for probing adduct stability. PMID- 4028328 TI - Integration of a mutant c-Ha-ras oncogene into C3H/10T1/2 cells and its relationship to tumorigenic transformation. AB - C3H/10T1/2-CL8 mouse cells were shown to take up and express a plasmid-cloned drug resistance gene (Ecogpt) after DNA transfection at a frequency (2-6 X 10(-4) which is acceptable for routine recovery of gene-transformed populations. Transfection of 10T1/2 cells with a mutant c-Ha-ras oncogene (pEJ6.6 plasmid) results in neoplastically transformed 10T1/2 cell populations as judged by colony morphology and tumorigenic growth in nude mice. The levels of mutant c-Ha-ras gene integration and expression in the tumorigenic cell populations and 10T1/2 cell controls were determined, and the highest level of mutant ras transcript was seen in the most tumorigenic cell population. A preliminary comparison of 10T1/2 and NIH/3T3 cells showed similar frequencies for pEJ 6.6-induced transformed foci and a similar lack of sensitivity to the transforming effects of a cloned B-lym oncogene. The results identify a genetic event, which has previously been shown to be carcinogen-inducible, that is permissive for neoplastic transformation of the widely used carcinogen-transformable 10T1/2 mouse cell line. PMID- 4028329 TI - H.p.l.c. of benzo[a]pyrene glucuronide, sulfate and glutathione conjugates and water-soluble metabolites from hamster embryo fibroblasts. AB - Chromatography of benzo[a]pyrene (BaP) sulfate, glucuronide and glutathione (GSH) conjugate standards were examined by h.p.l.c. on a C8 column as modified by various organic acids and solvents. Sulfate and glucuronide standards were positional isomers derived from BaP-1,3,6,7,9 phenols and BaP-GSH conjugates consisted of a racemic mixture of BaP-4,5-GSH. In the absence of acid, BaP conjugates appeared as rapidly eluting, unresolved peaks in aqueous-methanol or acetonitrile gradients or coeluted as broad peaks in a water-propanol gradient, with the exception of BaP-7-OH sulfate which eluted as a distinct symmetrical peak. Addition of acetic or trifluoroacetic (TFA) acids enhanced column retention of BaP conjugates in each solvent system. Upon acidification of mobile phases, BaP-GSH isomers were partially resolved, isomers of BaP sulfates or of BaP glucuronides coeluted, and BaP-7-OH sulfate was resolved from all conjugates. BaP GSH conjugates were most resolved and preceded elution of other conjugates when TFA was added to mobile phases. BaP sulfates and glucuronides generally coeluted but were partially resolved at 0.1% TFA in a water-methanol gradient. Water soluble metabolites from cultured hamster embryo fibroblasts (HEF) incubated with [3H]BaP for 24 h were chromatographed by h.p.l.c. in a water-methanol gradient with TFA. BaP glucuronides, consisting of tetraols, triols, quinones, dihydrodiols and phenols eluted as a single peak which could be removed by beta glucuronidase treatment and organic extraction. BaP sulfates were not detected. The remaining BaP metabolites which were resistant to enzymatic hydrolysis, generally eluted prior to BaP glucuronides suggesting they constitute a family of BaP-GSH derivatives. PMID- 4028330 TI - Nafenopin-induced rat liver peroxisome proliferation reduces DNA methylation by N nitrosodimethylamine in vivo. AB - The hypolipidaemic drug nafenopin (NAF) has been shown to enhance the hepatocarcinogenic effect of N-nitrosodimethylamine (NDMA) and N nitrosodiethylamine in rats. We have investigated whether the NAF-induced peroxisome proliferation in hepatocytes interferes with NDMA's metabolism and interaction with DNA. Adult male Wistar rats received a single i.p. injection of [14C]NDMA (2 mg/kg) and were killed 4 h later. DNA was isolated from liver and kidney, hydrolysed in 0.1 N HCl and analysed by Sephasorb chromatography. In rats pre-treated with NAF (0.2% in the diet over a period of 3 weeks), the concentration of N7-methylguanine in hepatic DNA (mumol/mol guanine) was 46% below control values. This is probably due to the greater amount of target DNA, as NAF caused a marked hepatomegaly with a 50% increase in total liver DNA content. Concentrations of N7-methylguanine in kidney DNA were twice as high in NAF-pre-treated animals when compared to control rats. This is unlikely to result from a shift in the metabolism of NDMA from liver to other rat tissues since the time course and extent of the conversion of [14C]NDMA to 14CO2 and 14C-labelled urinary metabolites were identical in NAF-treated and control animals. There was no indication that NAF inhibits the activity of the hepatic O6-alkylguanine-DNA alkyltransferase. PMID- 4028331 TI - The effect of some experimental parameters on the inhibition of metabolic cooperation by phorbol myristate acetate. AB - The effect of cell density, PMA exposure time, concentration, pre-exposure and binding activity on the recovery of V 79 HGPRT- Chinese hamster cells in the metabolic cooperation assay was determined. A PMA exposure interval of only 1 min resulted in maximum recovery of HGPRT- cells. PMA began to inhibit metabolic cooperation at a dose as low as 0.1 ng/ml final media concentration. The recovery of HGPRT- cells varied according to cell density in the presence or absence of PMA, although the magnitude of this effect was much greater in untreated cells. Pre-exposure of cells to PMA increased the recovery of both post-PMA-treated and non-treated HGPRT- cells in a dose-dependent manner. [3H]PMA was rapidly bound to or taken up by V 79 cells. These results suggest that the inhibitory effect of PMA on metabolic cooperation in V 79 cells involves receptor binding. PMID- 4028332 TI - Interaction between yeast cytochrome P-450 and chemical carcinogens. AB - The binding of various chemical carcinogens to the glucose-inducible form of cytochrome (cyt.) P-450 in Saccharomyces cerevisiae was examined with reference to known metabolism in mammalian systems. All the carcinogens examined gave spectral interactions with the yeast cytochrome. The carcinogens benzo[a]pyrene and cyclophosphamide gave Type I binding, while benzidine and 2-naphthylamine gave Type II binding spectra indicating binding at the haem group. Dimethylnitrosamine gave undetectable binding in yeast microsomal fractions, but a Type I binding spectrum was seen with purified cyt. P-450 preparations. The demonstration that these carcinogens bind to yeast cyt. P-450 is discussed in the light of their genotoxicity. PMID- 4028333 TI - Syncarcinogenic effects on the initiation of rat liver tumors by trans-4 acetylaminostilbene and 2-acetylaminofluorene. AB - Two carcinogenic aromatic amines with different organotropism were tested for syncarcinogenic effects in rat liver in an initiation-promotion experiment. Trans 4-acetylaminostilbene (AAS) and 2-acetylaminofluorene (AAF) were administered as initiators in four doses each either alone or sequentially combined in both orders. The promotion phase was started by partial hepatectomy and continued by adding phenobarbital (250 p.p.m.) to the drinking water for 26 weeks. The number/cm2 of tissue section and average size of hyperplastic foci, glucose-6 phosphatase-deficient and gamma-glutamyl-transpeptidase-positive foci were determined and a total area of lesions calculated during the promotion phase after 18 and 31 weeks, and in the post-promotion phase after 42 and 47 weeks. The synergistic effects of AAS and AAF were clearly more than additive if compared with the sum of the effects exerted by each compound individually. The sequence in which both initiators were administered remarkably influenced the development of lesions. They developed more rapidly and persisted longer in the post promotion phase when AAS was administered first and AAF second. In the final stage, enzyme altered foci increased in the livers of both combination groups, but to a greater extent in the AAS-AAF group. It is concluded that the two arylamides damage DNA independently. In addition, however, the results suggest that AAS acts predominantly as an initiator, and AAF as a weak initiator and a strong promoter in what is considered the initiation phase of this experiment. PMID- 4028334 TI - Enhancement of cholesterol synthesis and pentose phosphate pathway activity in proliferating hepatocyte nodules. AB - The endogenous synthesis of cholesterol in hepatocyte nodules, induced in male Wistar rats, by a single dose of the hepatocarcinogen diethylnitrosamine followed by a selection procedure, was investigated and was compared with that in surrounding and control tissue. In addition, the activity of enzymes related to carbohydrate metabolism (glucose-6-phosphate dehydrogenase, 6-phosphogluconate dehydrogenase, glucose-6-phosphatase and pyruvate kinase), was measured. Hepatocyte nodules showed a striking increase in their capacity for synthesizing cholesterol, in comparison to surrounding and control tissues, and an enhancement in the activity of the pentose phosphate pathway, as indicated by increased activity of glucose-6-phosphate dehydrogenase and of 6-phosphogluconate dehydrogenase, and a concomitant decrease of glucose-6-phosphatase. The stimulation of cholesterol synthesis and of the pentose phosphate pathway was associated with increased incorporation of labelled thymidine into DNA. These data indicate that, among other metabolic disturbances, enhancement of cholesterol synthesis and of the pentose phosphate pathway, is accompanied by an increased proliferative capacity of hepatocyte nodules. PMID- 4028335 TI - Mechanistic aspects of the delay in the G2 phase of the cell cycle caused by tumor promoter 12-O-tetradecanoylphorbol-13-acetate in HeLa cells. AB - In order to gain an insight into the nature of the radiomimetic activity by which the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) alters cell cycle parameters in HeLa cells, possibilities of modifying the TPA-induced G2 block and recovery from it were studied. TPA-induced G2 blockage was analysed by counting mitotic figures. It was not influenced by hydroxyurea (10(-3) M) thus indicating that it is independent of DNA synthesis. TPA-induced decrease of mitotic activity occurred faster than that caused by cycloheximide (10(-5) M) indicating that the TPA-sensitive transition point in G2 is closer to mitosis than that for cycloheximide. Superoxide dismutase, catalase, alpha-tocopherol, the radioprotector S-(2-aminoethyl)isothiuroniumbromide.HBr (AET), caffeine and indomethacin and eicosatetraynoic acid (ETYA), both inhibitors of oxygenases in the arachidonic acid cascade, were not capable of reducing the TPA-induced G2 response. Under certain conditions small concentrations of AET (10(-8) M) and ETYA (10(-8) M) appeared to improve recovery slightly. Mannitol and sorbitol, however, both hydroxyl radical scavengers at 0.1 M concentration reduced TPA effectiveness to a large degree (0.1 M D- and L-mannose were ineffective). Dimethylsulfoxide (0.1 M), another hydroxyl radical scavenger, was ineffective. PMID- 4028336 TI - Fetal mouse susceptibility to transplacental lung and liver carcinogenesis by 3 methylcholanthrene: positive correlation with responsiveness to inducers of aromatic hydrocarbon metabolism. AB - The role of metabolic activation of carcinogens in fetal tissue as a determinant of sensitivity in transplacental carcinogenesis was investigated in a pharmacogenetic experiment utilizing backcrosses of C57BL/6 (AhbAhb, responsive to induction of aromatic hydrocarbon metabolism) and DBA/2 (AhdAhd, non responsive) mice. Responsive (C57BL/6 X DBA/2)F1 and non-responsive DBA mothers, all carrying both responsive (AhbAhd) and non-responsive (AhdAhd) fetuses, were given i.p. doses of the carcinogen 3-methylcholanthrene (MC) ranging from 5 to 175 mg/kg on gestation day 17. At 10 months of age the metabolic phenotype of each offspring was determined, and correlated with number of lung and liver tumors. Both male and female AhbAhd (responsive) offspring in most dose groups presented a consistent two- to three-fold higher incidence of lung tumors than did non-responsive AhdAhd littermates. The difference held for offspring of both (C57BL/6 X DBA)F1 and DBA mothers and it was of statistical significance for one or both sexes at most dosage levels. Hepatocellular tumors were also significantly more frequent in responsive male AhbAhd progeny of (C57BL/6 X DBA/2)F1 mothers than in non-responsive AhdAhd littermates. Progeny of the DBA mothers exhibited significantly more liver and lung tumors than did those of the (C57BL/6 X DBA/2)F1 mothers receiving the same dose. These results suggest that in this model system both maternal and fetal genotype for responsiveness to induction of aromatic hydrocarbon metabolism are important factors modulating fetal carcinogenic risk. PMID- 4028337 TI - Carcinogenic effect of N-nitrosobis (2-oxopropyl)amine in newborn rats. AB - N-nitrosobis(2-oxopropyl)amine (BOP) was administered twice weekly for a total of 11 doses to 2-day-old Fischer F-344 rats of both sexes to ascertain the spectrum of tissues sensitive to its carcinogenic effects. At 26 weeks, the following incidence of neoplasms were encountered in male and females, respectively; hepatocellular carcinoma (53 and 46%); nephroblastoma (21 and 11%); and in males gonadal stromal tumors of testis (68%). Although acidophilic and basophilic acinar cell foci were encountered in pancreas, these were few in number and microscopic. These findings indicate that in newborn Fischer rats, hepatocytes, epithelial and mesenchymal cells of the kidney, and mesenchymal cells of testis are more sensitive to BOP than those of exocrine pancreas. PMID- 4028338 TI - Methylating agents: their target amino acids in nuclear proteins. AB - We have tried to establish a correlation between the carcinogenic potency of four methylating compounds and their specific target sites in chromatin. We have therefore compared the nuclear metabolism of two relatively weak carcinogens radioactively labelled: dimethyl sulphate (DMS) and methyl methanesulphonate (MMS), and two potent carcinogens: N-methyl-N-nitrosourea (MNU) and N-methyl-N' nitro-N-nitrosoguanosine (MNNG) in cultured primary hepatocytes and the V79 Chinese hamster cell line. Cysteine (when present), and to a lesser extent histidine, were methylated by MMS and DMS not only in the total acid-soluble nuclear protein (H) but also in purified histones H1 and H3. These compounds had the same effect not only on total non-histone nuclear protein (NH) but also on purified HMG1 and HMG2 (nuclear non-histone proteins with high electrophoretic mobility). Traces of methylarginine and methylated lysine could be detected in all samples. MNU and MNNG predominantly methylated lysine and arginine residues, the former being found mostly in acid soluble, the latter in non-histone nuclear protein. Methylated cysteine and histidine were present in trace amounts. Our preliminary data suggest specific amino acid methylation at the nuclear protein level for carcinogens with different potencies, similar to what has been found for DNA bases. PMID- 4028339 TI - Cerebral function in iron deficiency: a review. AB - Studies in many parts of the world have shown that children with iron deficiency and anaemia show minor defects of cerebral function such as poor attentiveness, poor coordination and slightly impaired scores on developmental assessment. The patients improve rapidly after treatment with iron--too quickly for their anaemia to have been corrected. Such changes have not been detected in children with anaemia from other causes, nor in patients with iron deficiency too slight to cause anaemia. The possibility that these changes are due in some way to some other aspect of malnutrition has not been excluded. Fortunately they are minimal, easily reversible and potentially preventable. PMID- 4028340 TI - Smoking habits in school-children with 2 years follow-up. AB - The proportion of smokers among Swedish school-children between 12 and 15 years of age and their short- and long-term attitudes and reactions towards smoking during an antismoking campaign was studied. Of a total of 413 pupils interviewed, 13.3% of the boys and 9.5% of the girls were smokers. Among the 15-year-old pupils 21% were smokers, whereas none of the 12-13-year-old pupils smoked at all. Everyday smoking was twice as common in boys as in girls but on follow-up there was no difference. Our study confirms a trend of diminishing smoking habits in boys but not among girls. Antitobacco campaigns may have a long-term positive effect in supporting changed attitudes towards smoking. PMID- 4028341 TI - Addicted mothers and their children: a case for coordinated welfare services. AB - Children of drug-addicted mothers are at an increased risk of premature birth, neonatal complications, developmental delay, understimulation, deprivation, neglect, abuse and even premature death. Research results from four Danish centres are presented and discussed. The material covers the period from 1970 1983. The studies clearly show a need for more coordinated support and services for these families and their children in order to prevent a new generation of 'social losers'. PMID- 4028342 TI - Ventricular action potentials, ventricular extracellular potentials, and the ECG of guinea pig. AB - Action potentials were recorded from different regions of the guinea pig ventricle to characterize regional differences in waveform configuration, and to acquire insight into the generation of the T-wave of the electrocardiogram. Isolated tissue preparations were driven at 1 Hz, and microelectrodes were used to map accessible surface regions of the epicardium, endocardium, and septum. There were minimal differences in regional resting potentials (mean -87 mV) and amplitudes (mean 122 mV), but Vmax in the epicardium (mean 110 V/sec) was much smaller than elsewhere (mean 247 V/sec). The action potential duration at the -80 mV repolarization level was longest in the papillary muscles (mean 154 msec), shortest in the septum (mean 126 msec), and generally 10-15 msec longer at the base than at the apex. The characteristics of intramural action potentials were inferred from measurements on enzymatically isolated myocytes, the rationale being that most dissociated myocytes originated from intramural cell layers. The action potentials in about 40% of the myocytes had durations similar to those recorded from the tissue surface (110-170 msec), and the remainder ranged from 170-290 msec long. The existence of longer-than-surface action potentials in the ventricle was also inferred from the body surface electrocardiogram and from bipolar electrograms of isolated left ventricles. In both cases, the Q-T intervals could be accounted for only by action potentials longer than those recorded from the ventricular surface. PMID- 4028343 TI - The effect of pH on cellular and membrane calcium binding and contraction of myocardium. A possible role for sarcolemmal phospholipid in EC coupling. AB - Calcium binding to cultured whole cell monolayers, to their membranes made by "gas dissection," and to sarcolemmal vesicles from canine heart, is measured as a function of pH from 5.5-8.5. The effects on binding are compared to the contraction response of the cultured cells over the same pH range. All responses to pH, including calcium binding and contraction, are well described (r = 0.98 0.99) by a relation in which calcium binding depends primarily upon the extent of ionization of sarcolemmal binding sites. The effect of pH on calcium binding to phospholipid extracted from sarcolemmal vesicles suggests that the phospholipid accounts for at least 75% of the binding. The extent of ionization of the sites is pH-dependent and predicted by a form of the Henderson-Hasselbach relation with pK of the putative sites between 6.60 and 7.15. As pH increases from 5.5-8.5, membranous calcium binding, cellular calcium uptake, and contraction amplitude increase proportionally. Cellular calcium uptake increases by 4.4 mmol/kg dry weight cells (0.75 mmol/kg wet weight). Sixty percent to 65% of this increment is rapidly exchangeable and lanthanum displaceable, indicative of sarcolemmal localization. The remainder enters a slowly exchangeable (t1/2 = 26 minutes) compartment not directly related to support of contraction. The study supports the hypothesis that calcium bound to sarcolemmal sites plays a critical role in control of myocardial contraction.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4028344 TI - Adverse effects of chronic cardiac denervation in conscious dogs with myocardial ischemia. AB - The extent to which total chronic cardiac denervation protects the ischemic myocardium was investigated in conscious dogs. The major hemodynamic difference after coronary artery occlusion was that left ventricular end-diastolic pressure rose significantly more, P less than 0.01, in the denervated group (12 +/- 1.5 mm Hg) than in the normal group (4.4 +/- 1.4 mm Hg). Blood flow (radioactive microspheres) in the ischemic endo- and epicardium fell to similar levels at 3-5 minutes after coronary occlusion, but was significantly less (P less than 0.01) in denervated dogs at 3 hours after occlusion in the endo- (0.05 +/- 0.01) and epicardium (0.30 +/- 0.02 ml/min per g), than in the endo- (0.13 +/- 0.03) and epicardium (0.42 +/- 0.05 ml/min per g) in the normal group. A subgroup of normal dogs was also studied, with left ventricular end-diastolic pressure increased by volume loading to levels similar to those observed in the denervated group after coronary occlusion; in these dogs, blood flow was similar to that in the other two groups 3-5 minutes after coronary artery occlusion, but, at 3 hours, was significantly more depressed (P less than 0.01) than that observed in normal dogs without volume loading in both endo- (0.03 +/- 0.01) and epicardial (0.25 +/- 0.03 ml/min per g) layers. Infarct size, as a fraction of the area at risk, was significantly greater (P less than 0.05) in the denervated group (60 +/- 4.3%) and in the subgroup of normal dogs with elevated left ventricular end-diastolic pressure (73 +/- 5.8%), compared with the normal group without volume loading (37 +/- 8.1%). Thus, in conscious dogs, total chronic cardiac denervation exerts an adverse effect on infarct size which may be related to the sustained elevation in left ventricular end-diastolic pressure and consequent impairment of collateral perfusion. PMID- 4028345 TI - Protamine inhibits capillary formation in growing rat hearts. AB - Various indices of capillary supply to the rat heart were studied in neonatal rats injected for 2 or 4 weeks with protamine sulfate in saline (subcutaneously, 60 mg/kg body weight, 2 times/day). Cardiac capillarization was evaluated not only by traditional indices for the capillary supply, such as mean capillary density and myocyte-to-capillary ratio, but also by a more advanced morphometric method of capillary domains. This method allows the estimation of both the average radius of the Krogh tissue cylinder and its variability, which reflects the heterogeneity of capillary spacing found to be an independent morphological determinant of oxygen diffusion in the tissue. The results were evaluated with respect to regional differences (subendocardial vs. middle section), age differences, and the effect of protamine. No regional differences in capillary supply were found in this experimental situation. Hearts from older rats had significantly decreased capillary supply, expressed as lower capillary density, larger capillary domains, and greater radius of the tissue cylinder. On the other hand, the heterogeneity of capillary spacing decreased significantly with age. Protamine-injected animals, when compared to their control littermates, had a significantly higher cell-to-capillary ratio, lower capillary density, larger capillary domains, greater radius of the tissue cylinder, and larger variability in capillary spacing. Thus, protamine was effective in impeding rapid capillary growth in the hearts from rats in the early postnatal period. Close to half of all the existing capillaries in the adult rat hearts are formed during the first 3-4 postnatal weeks. PMID- 4028346 TI - Reentrant ventricular arrhythmias in the late myocardial infarction period in the dog. 13. Correlation of activation and refractory maps. AB - Isochronal maps of ventricular activation were analyzed in dogs 3-5 days after ligation of the left anterior descending coronary artery utilizing a 64-channel multiplexer. Isochronal maps of the effective refractory period were determined from 62 epicardial sites and correlated with the activation maps. The ischemia occurring in the surviving epicardial layer prolonged refractoriness in a spatially nonuniform manner. The resulting pattern of refractoriness on the epicardial surface resembled concentric rings of isorefractoriness which increased in duration from the normal zone to the center of the ischemic zone. The formation of an arc of functional unidirectional conduction block occurred along the gradient of refractoriness and the exact location of the arc depended on the S1-S2 interval. When a short S1-S2 failed to induce reentry, fewer adjacent sites with sufficiently disparate refractoriness formed a smaller arc of block. A subsequent S3 encountered further nonuniformly shortened refractoriness (normal areas had shortened refractoriness greater than ischemic areas) and the arc of block was lengthened. This required a longer time for the wavefront to circulate around the arc. When it then reached the distal side of the arc, refractoriness had expired proximal to the arc and reentry occurred. Similarly, nonuniform shortening of refractoriness explained why one reentrant beat may or may not produce successive reentrant beats. Therefore, the spatial pattern of refractoriness forms the substrate for the arc of unidirectional conduction block that is fundamental to the development of ventricular reentry in this experimental model. PMID- 4028347 TI - Vagal chemoreflex coronary vasodilation evoked by stimulating pulmonary C-fibers in dogs. AB - We performed experiments on anesthetized, open-chest dogs to determine whether the pulmonary chemoreflex (bradycardia and systemic hypotension) evoked by stimulating pulmonary C-fibers also involves reflex changes in coronary vascular resistance. We perfused the circumflex coronary artery at constant pressure (usually 100 mm Hg) and recorded mean circumflex blood flow. Stimulation of pulmonary C-fibers by right atrial injection of capsaicin (10 micrograms/kg) decreased arterial blood pressure and heart rate and increased circumflex blood flow by 32-109% (P less than 0.001). Circumflex blood flow also increased, by 26 100% (P less than 0.001), when heart rate was kept constant by pacing. Coronary vasodilation was not secondary to the reflex decrease in arterial blood pressure. Injecting capsaicin (10 micrograms/kg) into the left atrium did not increase circumflex blood flow. Reflex coronary vasodilation could still be evoked when myelinated nerve fibers were blocked selectively by cooling the cervical vagus nerves to 7-8 degrees C but was abolished by cooling to 0 degrees C, by cutting the pulmonary vagal branches, or by giving atropine. Reducing coronary perfusion pressure shifted the stimulus (dose of capsaicin)-response (increase in coronary blood flow) curve to the right, but, even at low perfusion pressures, significant reflex vasodilation still occurred. Regional (transmural) distribution of myocardial blood flow was measured by the microsphere technique at various perfusion pressures. The endocardial:epicardial blood flow ratio decreased significantly as perfusion pressure was reduced, but was not altered by right atrial injection of capsaicin at any perfusion pressure. Our results indicate that stimulation of pulmonary C-fibers triggers reflex cholinergic vasodilation in all layers of the myocardium. PMID- 4028348 TI - Microneurographic studies of the mechanisms of sympathetic nerve responses to static exercise in humans. AB - The purpose of this study was to determine the contribution of muscle afferents and central command in regulating sympathetic nerve activity during static exercise in humans. In 20 healthy subjects, we recorded heart rate, arterial pressure, and efferent sympathetic nerve activity in the leg during arm exercise. Microelectrodes were inserted percutaneously into a fascicle of the peroneal nerve to measure sympathetic discharge to muscle. Measurements were obtained in nine subjects during sustained handgrip (30% maximal voluntary contraction) followed by relaxation or by arrested circulation of the forearm. Heart rate and arterial pressure increased during the first and second minutes of handgrip. Muscle sympathetic nerve activity increased from 261 +/- 46 to 504 +/- 97 units (mean +/- SE; units = burst frequency X amplitude; P less than 0.05) during the second minute of handgrip. During forearm ischemia following handgrip, heart rate returned promptly to control, whereas arterial pressure and muscle sympathetic nerve activity (631 +/- 115 units) remained elevated. In contrast, muscle sympathetic nerve activity returned toward control during relaxation without arrested circulation. These data indicate that muscle sympathetic nerve activity is increased by stimulation of chemically sensitive muscle afferents. To determine the influence of central command on muscle sympathetic nerve activity, we compared responses during an involuntary and a voluntary biceps contraction, each at 20% maximal voluntary contraction. Both maneuvers raised arterial pressure, but heart rate increased only during voluntary contraction. More importantly, muscle sympathetic nerve activity rose during involuntary contraction, but fell during voluntary effort.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4028349 TI - Mechanical properties of human pericardium. Differences in viscoelastic response when compared with canine pericardium. AB - Whereas most experiments on the mechanical function of the pericardium have been performed on dogs, very little is known about the applicability of those data to humans. To examine the tensile viscoelastic properties of fresh human pericardium, we have used the methods from our previous study of canine pericardium. Although the mechanical responses of canine and human pericardium were qualitatively similar, human pericardium displayed a significantly greater viscous character. Human pericardium was 7.3 times thicker than canine pericardium, but was more extensible in stress-strain tests, with lower stiffness at a given strain. The static (elastic) stiffness of human pericardium seems identical to that of canine pericardium; lower stiffness per unit thickness of the human tissue at predicted physiological stresses was almost exactly compensated by the greater wall thickness. This effect was also seen in data on fracture strength and stiffness. However, human pericardium displayed greater viscous responses than the canine tissue. This was seen in doubled cyclic hysteresis losses, and greater stress relaxation and creep. Our results suggest that experiments on the viscoelastic properties of canine pericardium may not be directly applicable to humans, especially where dynamic mechanical properties are most important: i.e., in studies of ventricular function and the time-course of pericardial effusions. PMID- 4028350 TI - A note on the relation of maximum upstroke velocity to peak inward current recorded by the voltage clamp. PMID- 4028351 TI - Comments on "Interpretation and physiological significance of diastolic coronary artery pressure-flow relationships in the canine coronary bed". PMID- 4028352 TI - Cardiovascular surgery 1984. Council on Cardiovascular Surgery, American Heart Association, Scientific Sessions. Miami Beach, Florida, November 12-15, 1984. PMID- 4028353 TI - Operative risk of mitral valve replacement: discriminant analysis of 1329 procedures. AB - The influence of 34 variables on the operative mortality rate for isolated mitral valve replacement (MVR) was assessed by univariate and multivariate logistic regression analysis. The physiologic lesions were classified as stenosis (20%, operative mortality rate 8 +/- 1%), regurgitation (44%, operative mortality rate 13 +/- 2%), and mixed (34%, operative mortality rate 8 +/- 1%). Functional class (NYHA), previous myocardial infarction, and hepatic dysfunction were powerful independent clinical determinants of operative mortality (p less than .001), along with age at operation and emergency operation (p = .001, p = .04). Concomitant coronary artery bypass grafting or tricuspid annuloplasty, angina, ischemic etiology, and physiologic lesion were not significant independent determinants of operative risk. Interestingly, year of operation, prosthetic valve dysfunction, and previous cardiac surgery had no important effect on operative mortality. Early operative risk for MVR was related to preoperative cardiac and hepatic function. Prior myocardial infarction substantially increased the risk even if the mitral valve disease was not ischemic in origin. Increased operative mortality rate in the subgroup with mitral regurgitation was related to advanced left ventricular failure and myocardial infarction rather than the etiology of the mitral regurgitation. These clinical factors coupled with more refined measurements of left ventricular systolic pump function (independent of loading conditions) should permit more intelligent decision making regarding the optimal timing of MVR, at least in terms of early operative risk. PMID- 4028354 TI - Morbidity and mortality in mitral valve surgery. AB - To develop strategies for the management of high-risk patients, contemporary risk factors for operative mortality and postoperative ventricular dysfunction were identified in 214 patients undergoing mitral valve surgery in 1982 and 1983. Thirty-eight preoperative and perioperative variables were prospectively collected and analyzed by univariate and multivariate statistics. The overall mortality was 4.6% and the incidence of postoperative low-output syndrome (LOS) was 18.7%. Forty-seven patients with coronary artery disease (CAD) had a higher mortality and incidence of LOS (as evidenced by the need for inotropic drugs or counterpulsation to maintain blood pressure) (those with CAD 15% mortality, 40% LOS; those without CAD 2% mortality, 13% LOS; p less than .05). The presence of unstable angina and ischemic mitral regurgitation further increased the risk. Age was also a predictor of outcome. Patients who died or had LOS were older (those who died, 65 +/- 7 years, those with LOS, 58 +/- 11 years) than patients who survived and did not have postoperative dysfunction (those who survived, 53 +/- 11; those with no LOS, 53 +/- 11; p less than .01). Mitral regurgitation was associated with a higher (p less than .05) mortality and incidence of LOS (mortality 10.5%, LOS 36%; n = 76) than was mitral stenosis (mortality 0%, LOS 4%; n = 74) or mixed lesions (mortality 3%, LOS 15%; n = 64). In patients without CAD, mitral regurgitation remained a significant predictor of mortality and ventricular dysfunction.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4028355 TI - Comparison of dysfunction with mechanical and porcine mitral valve prostheses. AB - We reviewed the incidence of dysfunction of the Smeloff-Cutter mechanical prosthetic valve and the Hancock porcine prosthetic valve in the mitral position. The Smeloff-Cutter valve was implanted from 1966 to 1972; 107 patients were discharged from the hospital and were at risk for dysfunction. Follow-up averaged 10 +/- 0.7 years SD. The Hancock valve was implanted from 1971 through 1984; 473 patients were at risk and follow-up averaged 4.7 +/- 3.4 years SD. Dysfunction of the Smeloff-Cutter valve occurred as thrombosis with incomplete poppet opening in 13 patients. Dysfunction of the Hancock valve occurred as primary tissue failure in 47 patients. At 10 years the freedom from dysfunction of the Smeloff-Cutter valve was 84 +/- 5% SE and that for the Hancock valve was 71 +/- 4% SE (p greater than .06). The mortality associated with dysfunction of the Smeloff-Cutter valve was 46%; mortality associated with dysfunction of the Hancock valve was 15% (p less than .02). At 10 years the Hancock valve had a greater incidence of dysfunction than the Smeloff-Cutter valve but this difference was not statistically significant. The mortality associated with dysfunction of the Smeloff-Cutter valve, however, was three times that associated with dysfunction of the Hancock valve. PMID- 4028356 TI - The value of the radionuclide angiogram in the prediction of perioperative myocardial infarction in patients undergoing lower extremity revascularization procedures. AB - To better define the group of patients at high risk of myocardial infarction (MI) and death associated with lower extremity revascularization procedures, resting gated blood pool studies were obtained in 100 such patients before surgery and results were correlated with the prevalence of perioperative MI. The results indicated that three patient groups could be distinguished on the basis of cardiac ejection fraction. Group I (n = 50) had preoperative ejection fractions ranging from 56% to 83%. None of the patients in group I suffered an acute perioperative MI. Group II (n = 42) comprised patients with ejection fractions ranging from 36% to 55%. There was a 19.0% prevalence of MI in group II, with one cardiac death. Group III included eight patients with ejection fractions ranging from 26% to 35%. There was a 75% prevalence of perioperative MI in these patients, with one cardiac death. All perioperative MIs occurred within the first 48 hr after surgery. Statistical analysis demonstrated a significantly higher prevalence of perioperative MI in patients with gated pool ejection fractions of 35% or less compared with the prevalence in patients with one or more of the other widely used clinical signs of increased cardiac operative risk (p less than .02). PMID- 4028357 TI - Clinical comparison of St. Jude and porcine aortic valve prostheses. AB - One hundred eighty-seven consecutive patients who had aortic valve replacement with either a St. Jude or porcine heterograft prosthesis were studied prospectively. The two groups were similar with respect to 67 clinical and operative factors, which allowed comparison of valve performance as an independent variable. Total follow-up was 6162 patient-months (mean 32 months, range 23 to 62, 99% complete). There were no statistical differences in symptomatic improvement or mortality by life-table analysis. Valve-related complications expressed as percent per patient-year included: reoperation, 0.6 St. Jude and 1.2 porcine; endocarditis, 1.1 and 0.9; regurgitant murmur, 3.4 and 2.7; hemolysis, 2.8 and 0.0; thromboembolism, 2.8 and 1.5 (all not significant); and hemorrhage, 7.9 and 2.4 (p less than .005). Anticoagulant-related bleeding was the only significant difference between the two valves in morbidity and mortality 32 to 34 months after operation. PMID- 4028358 TI - Comparative evaluation of aortic valve replacement with Starr, Bjork, and porcine valve prostheses. AB - Three groups of 100 consecutive patients with aortic valve disease who were operated on between 1974 and 1978 underwent long-term evaluation. There were 100 aortic valve replacements with porcine bioprosthetic valves (group I), 100 with Starr valves (group II), and 100 with Bjork valves (group III). There were no significant differences in the preoperative clinical conditions of the patients in the three groups. Cumulative follow-up was 1688 patient-years. Incidence of valve-related death at 8 years was 4 +/- 2.3% in group I, 13 +/- 3.6% in group II, and 13 +/- 3.8% in group III (p less than .05). At 8 years 95 +/- 2.8% of the patients in group I were free of thromboembolism, compared with 81 +/- 4.8% of those in group II and 84 +/- 4.2% of those in group III (p less than .002). The actuarial risk of a reoperation at 8 years was 16 +/- 6% in group I, 5 +/- 2% in group II, and 2 +/- 1.6% in group III (p less than .025 group I vs group III). At 8 years 98 +/- 1.2% of the patients in group I were free of anticoagulant-related complications, compared with 88 +/- 3.8% of those in group II and 86 +/- 3.9% of those in group III (p less than .005). We conclude that at 8 years porcine bioprosthetic valves performed better than mechanical valves, taking into consideration thromboembolism, anticoagulant-related hemorrhage, and valve related death. PMID- 4028359 TI - Hemodynamic performance of the Carpentier-Edwards pericardial valve in the aortic position in vivo. AB - The bovine pericardial valve was developed to improve the hemodynamic function of tissue valves. Eighty-one patients undergoing aortic valve replacement with the Carpentier-Edwards pericardial valve in the aortic position were studied intraoperatively. Mean gradient across the valve (mm Hg) decreased as valve size increased: size 19, 23.0 +/- 7.8; size 21, 19.7 +/- 6.6; size 23, 15.2 +/- 8.6; size 25, 13 +/- 4.0. Mean valve orifice area (cm2) increased as valve size increased: size 19, 1.1 +/- 0.4; size 21, 1.4 +/- 0.6; size 23, 2.0 +/- 0.7; size 25, 2.1 +/- 0.7. The mean transvalvular gradient, valve orifice area, and performance index increased as mean flow increased. The Carpentier-Edwards pericardial valve provides excellent hemodynamic performance that is acceptable even in size 19. PMID- 4028360 TI - Clinical correlates of atrial tachyarrhythmias after valve replacement for aortic stenosis. AB - One hundred eighteen consecutive patients undergoing valve replacement for aortic stenosis were analyzed to determine the incidence of and predisposing factors to postoperative atrial tachyarrhythmias. Univariate and multivariate analyses were performed on 70 clinical, hemodynamic, radiographic, electrocardiographic, operative, and postoperative variables. Forty-seven patients (40%) experienced atrial tachyarrhythmias at a median of 3 days after surgery (70% atrial fibrillation, 22% atrial flutter, and 6% junctional tachycardia). Preoperative descriptors associated with an increased prevalence of atrial tachyarrhythmias were age 70 years or older (p less than .02), mitral regurgitation (p less than .002), history of paroxysmal atrial fibrillation (p less than .03), or antiarrhythmic therapy (p less than .006), diabetes mellitus (p less than .01), and elevated pulmonary systolic, mean, and capillary wedge pressures (p less than .02, p less than .007, p less than .005). Postoperative descriptors were prolonged respirator therapy (p less than .001), use of catecholamines (p less than .01) or vasodilators (p less than .05), and prolonged stay in the intensive care unit (p less than .04). Multivariate analysis of these 12 variables showed advanced age, diabetes mellitus, and prolonged respirator use to be independently associated with atrial tachycardias and to predict them with a sensitivity of 62% and a specificity of 77%. Anticipation of atrial arrhythmias in patients with specific clinical descriptors may be used to guide prophylactic therapy. PMID- 4028361 TI - Combined cardiac and abdominal aortic surgery. AB - Patients with associated cardiac and abdominal aortic disease can undergo one or two separate operations for correction of both problems. The results of one (group A) and two separate operations (group B) were compared in 26 consecutive patients. There were 12 patients in group A and 14 patients in group B. Each patient underwent aortocoronary and aortofemoral bypass. In addition, three patients from group A and two patients from group B underwent cardiac valve surgery; three patients from group A and two patients from group B also had aortorenal bypass. There were no operative deaths and the complications were similar in both groups. The total amount of blood transfused in hospital, the length of stay in the operating room and intensive care unit, and the length of hospital stay were significantly shorter in group A. The average cost per patient in group A was approximately one-half of the average cost in group B. This combined approach for cardiac and abdominal aortic surgery is probably safe and is certainly cost effective. PMID- 4028362 TI - Urgent surgery for ventricular septal rupture complicating acute myocardial infarction. AB - Medical treatment of postinfarction ventricular septal rupture carries a high mortality. Delayed surgery can be done with good results but many patients die awaiting operation. In 1978 we decided that all such patients presenting to us should undergo urgent cardiac catheterization and surgery. Since then we have seen 22 such patients. Two decided against surgery and died in the hospital. Twenty agreed to surgery; in 15 of these an intra-aortic balloon pump was inserted before catheterization and in another four at the time of operation. Catheterization was performed without complication, and surgery was performed within 2 days of septal rupture in all 20 patients. Twelve patients (60%) survived hospitalization. Three patients died of pump failure shortly after surgery; five died after a second operation for free wall rupture (n = 2) or persistent or recurrent septal defect (n = 3). Two other patients survived reoperation. Survivors were significantly younger than nonsurvivors and had a higher cardiac index and a lower shunt ratio. At a mean follow-up of 47.9 months, there has been one late noncardiac death. Eleven patients survive, all in class I or II. We conclude that in patients with septal rupture urgent surgery results in improved near-term survival compared with known survival rates in medically treated patients. Early recurrent rupture is common and often disastrous and requires refinement in operative technique. Age, cardiac index, and shunt volume are related to surgical outcome. Hospital survivors do very well on a long-term basis. We recommend continuation of this aggressive approach. PMID- 4028363 TI - Myocardial recovery after hypothermic arrest: a comparison of oxygenated crystalloid to blood cardioplegia. The role of calcium. AB - We compared multidose crystalloid hyperkalemic cardioplegic solutions with and without added red cells in 24 canine hearts subjected to 5 hr of arrest at 10 degrees C. All cardioplegic solutions were fully oxygenated at 4 degrees C before delivery. Since blood cardioplegia contained Ca++ carried over with the red cells, Ca++ was added to the crystalloid solution in one group. The table below shows the hematocrit (HCT) and ionized Ca++ concentrations of the cardioplegic solutions, and coronary arteriovenous oxygen difference during infusion of cardioplegic solution (AVO2) (ml O2/100 ml). Recovery during reperfusion is shown as percent of prearrest left ventricular function (LVF) and prearrest myocardial ATP concentration. PMID- 4028364 TI - Surgical treatment of constrictive pericarditis: analysis of outcome and diagnostic error. AB - The records of 81 patients with a diagnosis of constrictive pericarditis who underwent surgical treatment were examined to assess the effectiveness of diagnosis and therapy. A false-positive diagnosis occurred in 10 patients (12%); seven had restrictive cardiomyopathy. Of 51 variables examined, only a low right ventricular end-diastolic pressure (RVEDP) significantly and independently predicted diagnostic error. Seventy-one patients with constrictive pericarditis underwent pericardiectomy. Mean follow-up was 4.7 years (maximum 12), and only two patients were untraceable. The study population was notable: 42 patients had visceral as well as parietal pericardial involvement; 32 had idiopathic disease and 25 had pericarditis related to radiation therapy. Results were favorable in 83% of the population. There were seven in-hospital deaths (10%). Actuarial survival estimates were 74% and 64% at 5 and 10 years, respectively. Compared with a normal population, the survival rate of patients with postradiation constrictive pericarditis was significantly inferior, whereas the survival rate of the remaining patients was not significantly different. Patients with constrictive pericarditis and restrictive cardiomyopathy did no better than those with restrictive cardiomyopathy alone. Additionally, patients in NYHA functional class IV had a significantly worse prognosis. Multivariate analysis of 38 preoperative variables identified high RVEDP as a significant independent predictor of in-hospital death, and renal dysfunction and diuretic use were significant independent predictors of overall poor outcome. Differentiation between the diagnosis of constrictive pericarditis and restrictive cardiomyopathy remains a problem. Radiation therapy, pericarditis with restrictive cardiomyopathy, high RVEDP, NYHA class IV status, renal dysfunction, and diuretic use adversely influenced outcome in patients undergoing pericardiectomy. PMID- 4028365 TI - The surgical treatment of endomyocardial fibrosis: results in 55 patients. AB - Over a 5 year period we have operated on 55 patients with endomyocardial fibrosis (EMF). The patients were from 4 to 56 years old (mean 13) and they were usually in poor condition at the time of surgery, with 47% in class III, and 24% in class IV with respect to cardiac function. They presented with right heart restrictive diastolic filling pattern (n = 17), mitral insufficiency (n = 18), or a combined syndrome (n = 20). All patients were operated upon during cardiopulmonary bypass and were submitted to a combination of the following procedures: endocardiectomy (30 right ventricular, 28 left ventricular), valvular replacement (21 tricuspid valve, 27 mitral valve), and/or valvuloplasty (10 mitral, five tricuspid). Nine patients, all with left ventricular or bilateral EMF, died in the postoperative period (16%), mainly of low cardiac output. There were five late deaths (three valve related). All other patients were functionally improved at the mean follow up of 32 months. Twenty-two underwent a late catheterization study. We conclude the following from our experience: EMF is a very severe disease that is seen mainly in childhood and adolescence, carries a poor spontaneous prognosis, and is frequently seen in tropical countries. Surgical treatment is beneficial, but surgical mortality is high. Our technical modifications have totally eliminated the occurrence of postoperative complete heart block. A conservative valvular procedure has been shown to be possible even in some patients with severe mitral insufficiency and left ventricular EMF. The late objective improvement is better in those with left ventricular EMF than in those with right ventricular EMF.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4028366 TI - Classic versus modified Blalock-Taussig shunts in neonates and infants. AB - Between July 1979 and October 1984, 61 systemic-pulmonary arterial shunts were created in 45 patients. Clinical and angiographic results with 23 classic Blalock Taussig shunts (BTSs) and 35 modified Blalock-Taussig shunts (MBTSs) with polytetrafluoroethylene grafts between the subclavian and pulmonary arteries were compared. Forty-three of the patients studied were infants: 28 were less than 1 month old, and 19 were less than 1 week old. Weights were 1.1 to 19 kg (mean 2.9 kg). Diagnoses were complex tetralogy of Fallot (18 patients), transposition of the great arteries with small left ventricle or left ventricular outflow tract obstruction (six patients) pulmonary atresia (seven patients) with intact ventricular septum (three) and ventricular septal defect (four), tricuspid atresia (four patients), univentricular heart (six patients), atrioventricular septal defect (canal) with pulmonary stenosis (three patients), and double-outlet right ventricle (one patient). Comparison groups were concurrent and were equivalent for age, weight, and complexity of anomaly. Patients were removed from the study population at the time of subsequent open heart surgery or at death. All patients were followed for a minimum of 6 months and for up to 5 1/2 years (BTS 1 1/2 to 5 1/2 years, mean 33 months; MBTS 6 months to 3 years, mean 20 months). There were no intraoperative deaths in either group. Among the 23 BTSs, three failed at 1, 3, and 19 days, resulting in two deaths (17%). One premature infant died despite a second shunt, one died during attempted intracardiac repair at 13 days of age, and the other was well after revision of the shunt. Eight patients underwent subsequent intracardiac repair 1 to 5 years (mean 34 months) after the initial procedure. Another four patients died from complex intracardiac anomalies with patent shunts. Three patients are alive 2 to 4 years after receiving shunts and have not undergone subsequent surgery. Late postoperative angiograms demonstrate a disturbing incidence (21%) of stenosis and right pulmonary arterial deformity despite satisfactory immediate postoperative studies and good clinical function. Eight patients required a second shunt, two for anatomic discontinuity of the pulmonary arteries and six because of inadequate blood flow through the first shunt. Among the 35 patients receiving the MBTS, two required early revision (technical error and ductal tissue at the anastomosis). There were no shunt-related deaths, but three (6%) occurred within 30 days of operation from left ventricular infarct, cerebral hemorrhage, sepsis, and severe aortic stenosis with arrhythmias.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 4028367 TI - Improved right ventricular function after intra-atrial repair of transposition of the great arteries. AB - Current interest in the arterial switch operation for simple transposition of the great arteries (TGA) has led us to evaluate our latest patients who have undergone intra-atrial repair. Right ventricular function and overall results were compared in 32 patients who had undergone the Senning procedure between 1978 and 1983 and 26 patients who had undergone Mustard repair between 1971 and 1978). Deep hypothermia and circulatory arrest were used in all Senning operations and in 18 of 26 Mustard procedures. Cardiac catheterization was performed an average of 1 year after surgery in all patients. Postoperative right ventricular ejection fraction (EF) was below normal (less than 0.49) in 16 of 32 patients who underwent the Senning procedure and averaged 0.48 +/- 0.09. In the patients in this group with abnormal right ventricular EFs after repair there was a fall in the value after surgery (0.51 to 0.40, p less than .001), while in those with normal right ventricular EFs after repair there was no change (0.57 to 0.55, NS). All 32 patients who underwent the Senning procedure were compared with 26 patients who underwent the Mustard operation (13 treated between 1971 and 1974 and 13 treated between 1975 and 1978). An older age at surgery (12 +/- 7 vs 6 +/- 8 months, p less than .006) and a lower preoperative right ventricular EF (0.46 +/- 0.09 vs 0.54 +/- 0.08, p less than .007) characterized the Mustard vs the Senning group.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4028368 TI - Surgical repair of Ebstein's anomaly: selection of patients and early and late operative results. AB - Between April 1972 and August 1984, 72 patients with Ebstein's malformation underwent surgery at a Mayo Clinic-affiliated hospital. In 58 (81%), plastic reconstruction of the tricuspid valve in which the anterior leaflet was used as a monocusp valve was possible. Eleven patients (15%) required a prosthetic valve (Hancock in 10; Starr-Edwards in one), and in three patients who had received a previous Glenn anastomosis, conversion to a Fontan type of arrangement was carried out. Age at operation ranged from 11 months to 64 years. There were five hospital deaths (6.9%) and three late, presumably arrhythmic, deaths. Follow-up of the initial 39 surgical survivors at least 2 years after the operation (mean, 5 years) revealed that 87% were in functional NYHA class I or II, a marked improvement over preoperative status. Surgical intervention is now recommended for all Ebstein's patients whose symptoms have deteriorated to NYHA class III or further. In addition, elective operation is recommended for less symptomatic patients in whom the cardiothoracic ratio has reached 0.65 or who are significantly cyanotic and polycythemic secondary to right-to-left shunting through an associated atrial septal defect. PMID- 4028369 TI - Replacement of obstructed right ventricular-pulmonary arterial valved conduits with nonvalved conduits in children. AB - Six to thirty percent of right ventricular-to-pulmonary arterial (RV-PA) valved conduits in children fail within 5 years. Experience with correction of tetralogy of Fallot has shown that a competent pulmonary valve is not essential for excellent late results in most patients. Between March 1980 and November 1984, 26 patients who were 12.5 +/- 3.3 years old underwent conduit replacement 6.7 +/- 2.4 years after definitive repair of congenital heart defects in which a xenograft RV-PA valved conduit had been used. A new Dacron tube graft (n = 15) or pericardial (n = 8), dura mater (n = 2), or Dacron patch (n = 1) over the previous conduit bed was used as replacement. Preoperative mean right ventricular systolic pressure was 90.5 +/- 20 mm Hg and mean gradient across the conduit was 67.9 +/- 24.5 mm Hg. After replacement with a nonvalved conduit, right ventricular systolic pressure was reduced to 45.2 +/- 10.8 mm Hg (p less than .001), with a gradient of 8.9 +/- 7.6 mm Hg (p less than .001). There were no operative deaths. Follow-up at 19.5 +/- 14.9 months (range = 0 to 53) showed that all patients were in New York Heart Association class I (n = 21) or class II (n = 5). In the absence of pulmonary hypertension, hypoplastic pulmonary arteries, significant right ventricular dysfunction, or unrepaired tricuspid regurgitation, replacement of an obstructed conduit with a nonvalved conduit gives excellent early results and may diminish the need for late reoperation. PMID- 4028370 TI - Outcome of the Fontan procedure in patients with tricuspid atresia. AB - Between 1973 and 1983, 90 patients with tricuspid atresia underwent the Fontan operation at the Mayo Clinic. Operative mortality was 12% overall and decreased to 7% during the second 5 year period. At postoperative follow-up of 65 patients (1 to 10 years, mean 4), 50 (86%) of 58 present survivors were in excellent condition. There had been seven late deaths. Catheterization 0.5 to 8 years (mean 2.7) postoperatively in 25 patients disclosed a mean right atrial pressure of 14 mm Hg (range 6 to 21) and a mean cardiac index at rest of 3.0 (range 1.8 to 4.2). Mean left ventricular end-diastolic pressure was 8.5 mm Hg postoperatively compared with 16.5 mm Hg preoperatively; the decrease was secondary to a decreased ventricular volume load (mean volume load index 10.2 preoperatively, 3.0 postoperatively). We recommend that patients with tricuspid atresia have the Fontan operation by age 6 years to protect myocardial function. PMID- 4028371 TI - Relationship of pulmonary artery size to mortality in patients undergoing the Fontan operation. AB - The size of the pulmonary arteries, measured intraoperatively, was correlated with operative mortality in 90 patients who underwent the Fontan operation. There was no significant difference in the cross-sectional area of the right and left pulmonary arteries/body surface area (PA index) between survivors and nonsurvivors. There was no significant difference in mortality rates between patients with a PA index greater than 250 and those with a PA index less than 250 mm2/m2. Survival was observed with cross-sectional area as low as 188 mm2/m2. PMID- 4028372 TI - Right heart assist by intermittent abdominal compression after surgery for congenital heart disease. AB - Right heart assist after open heart surgery in children can be accomplished by inflation of a balloon beneath a tight cloth wrap on the abdomen. This device can be inexpensively constructed of ordinary equipment found in the intensive care unit. This is a review of the use of intermittent abdominal compression in 14 children (mean age 19 +/- 15 months, mean weight 8 +/- 4 kg) after operation at Henrietta Egleston Hospital. Primary diagnoses were tricuspid atresia physiology in five, atrioventricular canal in four, truncus arteriosus in one, tetralogy of Fallot in one, ventricular septal defect (VSD) in one, D-transposition of the great arteries in one, and aortic-left ventricular tunnel with VSD in one. Compression was used for an average of 16.3 +/- 11.4 hr. Displacement of blood from the abdominal viscera to the central circulation by balloon inflation led to elevation of right atrial pressure by 3.6 +/- 1.8 mm Hg (p less than .001) and consequent elevation of mean arterial pressure by 9.8 +/- 5 mm Hg (p less than .001). Urine output was improved in almost every instance. In 11 surviving children, the net fluid intake and output balance in the first 12 hr after application of intermittent abdominal compression was -154 +/- 219 ml (p less than .05). This simple method of intermittent abdominal compression was effective after a variety of operations for treatment of congenital heart disease and was especially useful after the Fontan procedure. PMID- 4028373 TI - Comprehensive health care and noncardiovascular mortality: an unlikely explanation of the findings from the Hypertension Detection and Follow-up Program. PMID- 4028374 TI - A review of possible roles of the platelet 12-lipoxygenase. PMID- 4028375 TI - Adenosine diphosphate as a mediator of platelet aggregation in vivo: an editorial view. PMID- 4028376 TI - Death and other time-related events after valve replacement. AB - A total of 1533 patients received primary aortic and/or mitral valve replacement, with or without tricuspid valve surgery or other associated cardiac procedures, from January 1, 1975, to July 1, 1979. Actuarial survival at 5 years was 74%. The hazard function (instantaneous risk) of death was highest immediately after operation. Among the incremental risk factors for premature death from any cause were preoperative NYHA class, any valve lesion other than aortic stenosis, aortic cross-clamp time, and combined aortic and mitral valve replacement. Ten modes of death were identified, each with its unique hazard function and risk factors. The commonest mode was cardiac failure. Sudden death was the next commonest, and the early phase of its hazard function peaked about 3 weeks after operation. Seventy five patients (6.7% of the 1533) had 103 valve reoperations in the follow-up period. Actuarial survival after reoperation was less than that after the primary operation; whether the reoperation was the first, second, or third was a risk factor. Actuarial freedom from prosthetic valve endocarditis (PVE) was 97% at 1 year, and that of periprosthetic leakage without evident infection was 98.8%; the hazard function for the event PVE had an early phase peaking at about 6 weeks and a constant low phase throughout, whereas that of periprosthetic leakage had a single early peaking phase. After reoperations, the actuarial freedom from PVE and periprosthetic leakage was less than that after the original operation. The risk factors for the development of periprosthetic leakage without evident infection were similar but not identical to those for PVE. Among patients receiving a bioprosthesis, 91% were free of bioprosthetic degeneration 5 years after operation. The hazard function was single and continuously rising, and young age and female gender were risk factors. Actuarial freedom from acute prosthetic thrombosis was 97.9% at 5 years. The single hazard function for this event peaked at 10 months. The risk of thrombosis was higher in female patients. The uses of this integrated study, and the inferences from it, are described. PMID- 4028377 TI - Noninvasively diagnosed peripheral arterial disease as a predictor of mortality: results from a prospective study. AB - Intermittent claudication has been reported in previous studies to approximately double the risk of subsequent mortality. However, a history of claudication is often present in the absence of significant peripheral arterial disease (PAD) and absent in the presence of PAD. For this reason we evaluated the association between large-vessel and small-vessel PAD, measured by highly reliable and valid noninvasive tests, and mortality in 567 older subjects from a defined population followed-up for an average of 4 years. Large-vessel PAD was strongly and significantly predictive of all-cause mortality in both men and women with a relative risk of 4 to 5, and this finding was independent of other cardiovascular disease risk factors in multivariable analysis. In addition, this finding persisted after exclusion of subjects with extant cardiovascular disease at baseline. The associations of both claudication and abnormal peripheral pulses with mortality were weaker than the large-vessel PAD association. Isolated small vessel PAD was unrelated to subsequent mortality. These findings suggest older subjects of both sexes at a high risk of impending mortality can be identified through noninvasive testing for large-vessel PAD. PMID- 4028379 TI - Subendocardial infarction in retrospect: pathologic, cardiographic, and ancillary features. AB - Fifty-three patients with subendocardial infarction (SEMI) were studied at autopsy; all were elderly and the group was equally divided by sex. About half had more than one SEMI; the recurrences or extensions often involved superjacent, but not infrequently adjacent, areas. Six showed fibrinous pericarditis. This larger study showed more widespread and severe coronary narrowing than an earlier report. Six patients had thrombi in the right coronary artery. Six showed electrocardiographic evidence of concomitant anteroseptal and inferior (Roesler Dressler) infarction, and 12 had intraventricular block generally preceding higher-grade block or arrhythmias. At some time during their terminal hospitalization, 27 patients, or half, developed distinctive protracted RS-T depression or T wave inversion. Twenty-four of the SEMIs were diagnosed on accepted criteria as transmural infarct; that diagnosis was sustained in only four. Thus neither the presence of changes in RS-T segment or T wave nor the absence of QRS changes are mandatory for the diagnosis of SEMI; this invalidates the common assumption that the diagnosis is not justified unless these conditions are met. PMID- 4028378 TI - Prognostic significance and natural history of left ventricular thrombi in patients with acute anterior myocardial infarction: a two-dimensional echocardiographic study. AB - Fifty-eight patients with transmural anterior myocardial infarction were prospectively studied with serial two-dimensional echocardiography to determine the clinical implications and prognostic significance of detection of left ventricular thrombus during acute myocardial infarction, the incidence of systemic embolization, and the possible occurrence of spontaneous regression of left ventricular thrombi. Patients were not treated with anticoagulants or platelet inhibitors during the acute phase of infarction or during follow-up. Two dimensional echocardiograms were obtained within 24 hr of myocardial infarction, every 24 hr until day 5, every 48 hr until day 15, and every month for a follow up of 2 to 11 months (mean 7), in the surviving patients; a total of 774 echocardiograms were obtained. Left ventricular thrombi were identified in 24 (41%) of the 58 study patients, and developed within 48 hr of infarction in 11 of these patients. Ten (91%) of the 11 patients with early thrombus formation died during hospitalization or during follow-up, while only two (15%) of the 13 who developed a thrombus after 48 hr of infarction died (p less than .005). Incidence of Killip class III or IV, total lactic dehydrogenase values, and extent of wall motion abnormalities were significantly higher in patients who developed a thrombus within 48 hr of infarction than in patients without thrombus. On the other hand, in patients who developed a thrombus after 48 hr of infarction, these parameters were not significantly different from those in patients who did not develop a thrombus. Spontaneous regression of thrombi was documented in three (20%) of the 15 patients who survived the acute phase of myocardial infarction.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4028380 TI - Detection of local abnormalities in ventricular activation sequence by body surface isochrone mapping in patients with previous myocardial infarction. AB - Body surface isochrone mapping was performed in 36 normal subjects and in 85 patients with previous myocardial infarction. Eighty-seven unipolar electrocardiograms distributed over the anterior chest and the back were recorded simultaneously. For each lead, activation time was measured as the time from the onset of QRS to the peak of the R wave. The lead points where R waves were not observed were designated the "no R wave area" (NR area). Isochrone maps of normal subjects had a consistent pattern, with isochrone lines extending from the right upper anterior chest to the left anterior chest and then to the back. NR area was small and was located only on the right upper chest or the upper back. On the isochrone maps of patients with myocardial infarction, abnormal findings were observed; NR area was found in 26 of 28 patients with anterior infarction on the upper to middle anterior chest, in 13 of 22 patients with inferior infarction on the lower chest, and in 24 of 25 patients with anterior and inferior infarction on the upper to lower anterior chest. Activation time was delayed near the NR area (peri-NR area delay) in 37 patients. In patients with apical infarction, an islandlike zone of delayed activation was typically found on the left precordium. These abnormal patterns are considered to indicate local abnormalities in the activation of infarcted myocardium; the NR area indicates dead unexcitable scar, and the peri-NR area delay and islandlike zone of delayed activation indicate partially infarcted myocardium of slow activation. Patients with NR area had greater degree of left ventricular asynergy and lower ejection fraction than those without.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4028381 TI - Senning repair for transposition of the great arteries in the first week of life. AB - Infants with D-loop transposition of the great arteries (D-TGA) may have unacceptable results after the balloon septostomy while awaiting surgery. It has been our policy to repair defects in infants with D-TGA and intact ventricular septum or small ventricular septal defect at the time of diagnosis. We report our experience with the Senning operation in 18 newborns less than 1 week of age. The mean age at operation was 3 days (range 12 hr to 7 days) and the mean weight was 3.5 kg (range 2.8 to 4.8). There were two early postoperative deaths (11%) and one late death (5%). Early mortality was associated with preoperative acidosis and congestive heart failure. Late mortality was associated with severe left ventricular outflow tract obstruction (LVOTO). The 15 long-term survivors have been followed for an average of 27 months and 11 of the 16 perioperative survivors have undergone postoperative catheterizations. There was no evidence of systemic or pulmonary venous obstruction. One patient developed LVOTO that led to his death. Two patients had residual atrial shunts. Electrocardiograms revealed no major arrhythmias. All patients are clinically asymptomatic. Good hemodynamic, electrocardiographic, and clinical results can be obtained with correction of D TGA in the first week of life. PMID- 4028382 TI - Exercise thallium-201 scintigraphy in dogs: effects of long-term coronary occlusion and collateral development on early and late scintigraphic images. AB - To examine the effects of coronary collateral development on thallium-201 (201Tl) distribution the left circumflex coronary artery was ligated in eight dogs. Three days later these animals ran on a treadmill, and 201-thallous chloride was injected into the right atrium at peak exercise. Scintigraphic scanning was begun within 10 min and continued for 3 hr. Scanning was repeated weekly for 6 weeks. In the last week radioactive microspheres were injected into the left atrium at peak exercise to measure regional myocardial blood flow. The scintigraphically determined disparity between perfusion of the ischemic and normal myocardium was most marked at 3 days after ligation. This difference gradually lessened over the first 4 weeks until there was no difference in 201Tl distribution to normally perfused myocardium and tissue distal to the ligation. Concomitant with the improvement in the scintigrams, exercise hemodynamics also improved over this 4 week period with significant increases in cardiac output and decreases in left atrial pressure. Serial coronary angiographic studies in two animals demonstrated the appearance of collaterals in the initial weeks after coronary occlusion, and by 4 weeks the left circumflex artery distal to the obstruction was completely opacified by collateral flow. The ratio of directly measured exercise blood flow to the left circumflex and normally perfused tissues was 0.89 +/- 0.08 at 6 weeks after ligation. Scintigraphic 201Tl redistribution after 3 hr also changed over the weeks after ligation. Three days after ligation washout from the ischemic area was significantly slower than that from the normal myocardium. By 6 weeks loss of 201Tl from the two regions occurred at nearly equal rates. Thus myocardial perfusion and function during exercise after coronary occlusion are dynamic events that change with time. It is likely that coronary collateral development is responsible for these phenomena. Therefore coronary collaterals do have salutary effects in the dog. PMID- 4028383 TI - Frequency-dependent effects of amitriptyline on ventricular conduction and cardiac rhythm in dogs. AB - Although overdoses of tricyclic antidepressant are known to produce both sinus tachycardia and ventricular tachyarrhythmias in man, these have been assumed to occur by independent mechanisms. This study was designed to evaluate the relationship of ventricular activation frequency to the cardiotoxic effects of amitriptyline. When amitriptyline was infused into dogs with formalin-induced atrioventricular (AV) block to evaluate a broad range of pacing frequencies, the drug produced dose-related QRS prolongation that was markedly frequency dependent. Similar frequency-dependent depression of the maximum rate of depolarization (Vmax) was noted for canine Purkinje fibers superfused with amitriptyline in vitro. The time constant of recovery from amitriptyline-induced block was dose independent and averaged 228 msec in vivo and 216 msec in vitro. When amitriptyline was infused into dogs with intact AV conduction, sinus tachycardia occurred within 15 min, followed by progressive QRS prolongation and ventricular tachyarrhythmias after an average 29 min. Slowing of sinus rate by vagal stimulation (seven dogs) or intravenous metoprolol (five dogs) reproducibly reversed the QRS prolongation and ventricular tachyarrhythmias caused by amitriptyline. These studies show that amitriptyline produces frequency-related depression of ventricular conduction in vivo, with a time dependence similar to effects on the maximum rate of depolarization in vitro. Interventions that slow heart rate reverse the adverse effects of amitriptyline on ventricular conduction and cardiac rhythm. PMID- 4028384 TI - Enhancement of recovery of myocardial function by oxygen free-radical scavengers after reversible regional ischemia. AB - Reperfusion after reversible regional ischemia has been shown to result in delayed recovery of myocardial function, but the mechanism responsible for this phenomenon remains unknown. We explored the potential role of oxygen-free radicals as mediators of postischemic dysfunction in open-chest dogs undergoing a 15 min occlusion of the left anterior descending coronary artery (LAD) followed by 2 hr of reperfusion. Treated animals (n = 19) received an infusion of the oxygen free-radical scavengers superoxide dismutase (SOD; 15,000 U/kg) and catalase (CAT; 55,000 U/kg) for 1 hr starting 15 min before LAD occlusion, while control animals (n = 20) received an equal volume of saline. SOD and CAT produced no discernible effect on heart rate, aortic pressure, or left atrial pressure. Collateral flow to the ischemic zone (radioactive microspheres) was 0.07 +/- 0.01 ml/min/g in both groups. The size of the occluded bed as determined by postmortem perfusion was 26.1 +/- 1.2% of the left ventricle in the control group and 26.5 +/- 0.9% in the treated group. Systolic wall thickening (an index of regional function) was assessed with an epicardial pulsed-Doppler probe. The two groups exhibited comparable systolic thickening under baseline conditions and similar degrees of dyskinesia during ischemia. Nevertheless, recovery of function (expressed as percent of baseline) was considerably greater in the treated dogs, both at 1 hr (43.8 +/- 14.3 vs 12.8 +/- 11.6) and 2 hr of reperfusion (74.2 +/- 8.4 vs 31.6 +/- 9.8, p less than .005). This improved recovery of function obtained with SOD and CAT suggests that oxygen-free radicals play an important role in the genesis of myocardial dysfunction after a brief episode of regional ischemia. PMID- 4028385 TI - Effect of serial brief ischemic episodes on extracellular K+, pH, and activation in the pig. AB - This study was performed to determine the reproducibility of the ionic and electrical changes associated with serial ischemic episodes. We used ion selective and bipolar plunge electrodes to determine the changes in left ventricular extracellular potassium ([K+]e), extracellular pH (pHe), and local activation during sequential 10 min occlusions of the left anterior descending coronary artery separated by 50 min of reperfusion in open-chest anesthetized pigs. We found that uniformly during the initial occlusion, and in approximately 50% of animals during the second occlusion, [K+]e rose more rapidly but to a lower level than in subsequent occlusions. By the third occlusion the changes in [K+]e were reproducible. Extracellular acidosis was greatest in the first occlusion and decreased progressively with each subsequent occlusion. Local activation was characterized by a decrease in spontaneous improvement and increase in block with each successive occlusion. The occurrence of ventricular fibrillation could not be directly attributed to the magnitude of the change in [K+]e or pHe. Moreover, the occurrence of ventricular fibrillation in one occlusion did not necessarily predict its occurrence thereafter. Our results indicate that serial episodes of ischemia are associated with different but predictable changes in ionic and electrical events that may be clinically relevant and that must be appreciated before the results from similar protocols with serial ischemic episodes can be interpreted meaningfully. PMID- 4028386 TI - Autonomic control of ventricular tachycardia: sympathetic neural influence on spontaneous tachycardia 24 hours after coronary occlusion. AB - This study was performed to determine whether sympathetic nerves influence the rate of ventricular tachycardia occurring spontaneously in dogs 24 hr after occlusion of the anterior descending coronary artery. Seventeen chloralose anesthetized dogs underwent activation mapping during spontaneous ventricular tachycardia with QRS morphologies similar to those recorded in the conscious state. Bilateral stellate ganglionectomy (n = 8) decreased mean arterial pressure from 71 +/- 4 (mean +/- SE) to 52 +/- 5 mm Hg (p less than .001) and heart rate from 121 +/- 9 to 79 +/- 15 beats/min (p less than .025) by decreasing the number of complexes of ventricular tachycardia from 120 +/- 9 to 49 +/- 15 per minute (p less than .001). Subsequent unilateral sympathetic nerve stimulation (n = 4) was shown to accelerate ventricular tachycardia foci originating from the ipsilateral aspect of the infarction. Regional sympathetic denervation (n = 7) was performed by application of phenol to the epicardium surrounding an electrode at the site of origin of at least one morphology of ventricular tachycardia. Mean arterial pressure did not change, but total heart rate decreased from 122 +/- 9 to 106 +/- 9 beats/min (p less than .01) and the number of complexes of ventricular tachycardia with a morphology arising from the phenol-treated area fell from 68 +/- 12 to 28 +/- 9 (p less than .001). Evidence for regional denervation was documented by prolongation of duration of electrograms and local repolarization times limited to the phenol-treated area. We conclude that sympathetic nerves directly control rate of spontaneous ventricular tachycardia 24 hr after myocardial infarction in the dog. PMID- 4028387 TI - Insect sting anaphylaxis in patients without detectable serum venom-specific IgE. AB - Following insect sting anaphylaxis, twenty-five patients of over 500 evaluated, did not have detectable serum venom-specific IgE. Twenty-two were evaluated within 1 year of the reaction, fifteen within 6 months. Anaphylaxis occurred in six patients after their first sting exposure. The clinical features of the sting reaction were typical of the reaction occurring in insect-allergic patients with serum venom-specific IgE. Eleven of the twenty-five patients had negative venom skin tests. These observations suggest that a non-IgE mechanism may be responsible for a minority of insect sting reactions. PMID- 4028388 TI - Specific IgE to food and inhalant allergens in intestinal washings of children affected by atopic eczema. AB - Serum and rectal total and specific IgE were measured in eleven children with atopic dermatitis and eight with atopic dermatitis and associated wheezing. Specific IgE to food and inhalant allergens in rectal washings were found in fourteen patients. Of the seventy-six allergens which gave positive results, twenty were positive in both serum and intestine, thirty in serum alone and twenty-six in intestines alone. Specific intestinal IgE were confirmed by food challenge in three out of four patients whose skin-prick test and serum RAST were both negative. Local production of these antibodies was demonstrated by the 'double ratio' of Deuschl and Johansson, and the 'specific activity ratio' of Platts-Mills. Positive ratios (greater than 1) were obtained with both formulas for twelve of fourteen allergens tested. These data suggest that gut-associated lymphoid tissue may play a role in the pathogenesis of atopic disease. PMID- 4028389 TI - Analysis of tobacco leaf allergens by crossed radioimmunoelectrophoresis. AB - The reactivity of eleven 'tobacco smoke sensitive' and eight 'non-sensitive' individuals to tobacco leaf allergens was tested by Crossed Radioimmunoelectrophoresis (CRIE). All nineteen study subjects had IgE antibodies to tobacco leaf antigens as measured by Radioallergosorbent Test (RAST) and seventeen of the nineteen individuals were atopic. Of the thirty-seven tobacco leaf precipitins detected by Cross Immunoelectrophoresis (CIE), three were identified as allergens by CRIE. All nineteen subjects reacted to at least one of the three allergens detected. However, neither the intensity nor the incidence of reactivity with any of the three allergens correlated with smoking or 'smoke sensitivity'. PMID- 4028390 TI - Asthma and the month of birth. PMID- 4028391 TI - A highly sensitive immunoassay system involving antibody-coated tubes and liposome-entrapped dye. AB - In this colorimetric immunoassay for digoxin, large, unilamellar phospholipid vesicles approximately 0.2 micron in diameter are loaded with high concentrations of Sulforhodamine B. Digoxigenin coupled to phosphatidylethanolamine, incorporated into the lipid formulation, confers immunological specificity. The liposomes are then used as tracers in simple competitive-binding immunoassays with antibody-coated tubes. Results are amplified by 10(3) to 10(4) of what could be achieved with one label group attached to each hapten, so that the results can be read spectrophotometrically. The stability of the liposomes is excellent. The method should be applicable to measuring a wide variety of analytes. PMID- 4028392 TI - ImmunoConcentration--a new format for solid-phase immunoassays. AB - A new format for solid-phase immunoassays has been developed in which a monoclonal antibody-coated membrane, incorporated into a cylindrical, disposable device, regulates sample and reagent delivery. We illustrate the method with a two-site, immunoenzymometric assay that can detect human choriogonadotropin at less than 50 int. units/L (4 micrograms/L) in urine and less than 25 int. units/L (2 micrograms/L) in serum and takes less than 5 min to perform. The solid-phase antibody is located in a circular area in the center of the membrane so that in the presence of the hormone, after addition of substrate, a blue enzyme product is generated in this circular area. The high ratio of surface area to volume within the microporous matrix of the membrane assures short diffusion distances and therefore rapid binding of liquid-phase reagents to the solid phase. Pseudo first-order reaction kinetics describe the binding of antigen to immobilized antibody and the binding of enzyme-labeled antibody to immobilized antigen. The speed and simplicity of this format may facilitate testing for many analytes, both soluble and particulate, as well as serological testing. PMID- 4028393 TI - Capsule chemistry technology for high-speed clinical chemistry analyses. AB - We describe a new analytical approach--"capsule chemistry"--for high-speed, selective analysis of a wide variety of analytes. Sequential micro-aliquots of sample and reagents are encapsulated within an inert fluorocarbon liquid. The resulting "test capsule" is introduced into a single analytical flow path, composed of a solid fluorocarbon, Teflon, where the sample is incubated, mixed, reacted, and measured as a moving series of individual tests. These randomly selective assays are processed at a rate of 720 per hour. The unique physical interaction between the liquid and solid fluorocarbon carrier materials effectively prevents detectable "carryover" of aqueous constituents between the successive test capsules. Reactions are monitored through the walls of the Teflon analytical channel at nine in-line detector stations for colorimetric and nephelometric measurements. PMID- 4028394 TI - Two-dimensional centrifugation for desk-top clinical chemistry. AB - We have developed a new system for clinical chemistry analysis, the Vision System, in which centrifugal force is used to separate whole blood, measure reagent and plasma volumes, and complete all steps required for a spectrophotometric analysis. The system is based on use of a multichambered plastic test pack containing liquid reagents, which can be centrifuged at 500 X g in two planes, oriented at right angles to each other. Alternating centrifugal fields allows liquid reagents and plasma to flow into highly precise measuring and mixing chambers. A unique flash lamp and diode array spectrometer provide for optical measurements of 10 test packs at as many as eight wavelengths simultaneously. The temperature of each individual test pack is controlled by using a flash lamp coupled to a liquid crystal temperature sensor. Microprocessor control allows as many as 10 different chemistry reactions to be measured simultaneously on whole-blood, plasma, or serum samples. Comparison with results by an established batch-photometric analyzer demonstrated excellent precision and accuracy for various clinical chemistry tests. PMID- 4028395 TI - Colorimetric determination of potassium in whole blood, serum, and plasma. AB - This spectrophotometric method for the direct determination of potassium in serum or plasma is based on the selective complexing of potassium by a specific macrocyclic polyether, with the subsequent formation of an ion-pair with a colored anion. The colored anion is extracted into an organic solvent, clarified by centrifugation, and then measured at 415 nm. The absorbance of the chromogen varies linearly with [K+] to at least 15 mmol/L. Results of this colorimetric method (y) correlate well with the results obtained by a flame-photometric method (y = 1.04x - 0.22, r = 0.97, n = 81), with CVs ranging from 2 to 4%. We observed no interferences from lipemia, added bilirubin, or various electrolytes. We also evaluated the use of this reagent in a new automated blood analyzer developed by Abbott, a two-dimensional centrifugal system (Clin Chem 31:1457-1463, 1985). Potassium determined with this system (y) correlated well with results by flame photometry: y = 1.02x + 0.02 (r = 0.94, n = 168). With this system one can use whole-blood specimens in measuring potassium. PMID- 4028396 TI - A quantitative automated immunoassay for fibrinogen/fibrin degradation products. AB - We describe a prototype quantitative automated assay for fibrin and fibrinogen degradation products, a particle-enhanced turbidimetric inhibition immunoassay (PETINIA) in the Du Pont aca discrete clinical analyzer. This assay involves a latex particle reagent with covalently bound fibrinogen and a polyclonal antiserum raised in rabbits against human fibrinogen. A special secondary sample collection tube quantitatively removes fibrinogen from citrated plasma and inhibits further fibrinolysis, independent of heparin concentration. The assay range is 0-100 mg/L, in fibrinogen equivalents. The CV for the assay is less than 10% when performed with the aca. Nonclottable fibrin and fibrinogen fragments are measured by the assay, the greatest sensitivity being directed at the E domain of the fibrinogen molecule. We illustrate with case studies the potential of this assay for providing clinical information not obtainable with currently available qualitative and semi-quantitative assays. PMID- 4028397 TI - A nephelometry system for the Abbott TDx analyzer. AB - A self-contained light-scattering accessory carousel has been developed for the Abbott TDx fluorescence polarization analyzer, extending the instrument's capabilities to nephelometric methods of analysis, including assays for specific proteins by immunoprecipitation: IgG, IgA, IgM, and transferrin. The scattered light from a green-light-emitting diode (peak wavelength 565 nm) is measured at an angle of 37.5 degrees by the existing optical detection system of the TDx analyzer without modification of the instrument. Measurements are made at quasi equilibrium, with sample blank correction. No sample pretreatment is required, and antigen-excess is checked automatically. CVs range from 3 to 6% (within-run) and 7 to 9%. (total). Calibration curves may be stored for at least two weeks. A nephelometric method for monitoring chromogenic reactions in the green wavelength region is also described. This method--Scattered Energy Attenuation (SEA)--has been used in preliminary experiments to measure calcium, total protein, iron, and bilirubin. PMID- 4028399 TI - Simultaneous determination of total IgE and allergen-specific IgE in serum by the MAST chemiluminescent assay system. AB - We have developed a chemiluminescent immunoenzymometric system. The first commercial application of this chemiluminescent assay (CLA) is the measurement of total IgE and allergen-specific IgE in human serum. The CLA system is a second generation adaptation of the MAST RIA allergy profiling system. The MAST CLA system assay protocol consists of three steps: overnight incubation of serum, a 4 h incubation with enzyme-labeled antibody, and a 30-min chemiluminescent reaction, which produces a visible image (immunograph) on high-speed Polaroid instant film. The densities of the bands produced on the film are quantified with an inexpensive microprocessor-controlled infrared transmittance densitometer. The novel luminogenic substrates used yield a constant light output for over 2 h with an intensity at least 10-fold greater than that of commercial chemiluminescent reagents. The MAST CLA system exhibits sensitivity, specificity, and precision equal to that of the MAST RIA system (r = 0.96 for 40 serum samples analyzed with 25 allergens). As many as 35 different allergens per sample can be quantified in a single assay. The MAST CLA system requires no standard curve or volume dependent pipetting steps, incorporates both positive and negative controls for each sample, and quantifies allergen-specific IgE at picomolar concentrations. PMID- 4028398 TI - "The Yellow IRIS" urinalysis workstation--the first commercial application of "automated intelligent microscopy". AB - Since 1982, "automated intelligence microscopy" (AIM) has been refined and adapted to perform the portion of the urinalysis profile traditionally done by a microscope. AIM and analytical subsystems measuring relative density and performing dipstick chemistry compose the main elements of "The Yellow IRIS" urinalysis workstation, an attended system for automation and standardization of routine urinalysis. Performance data gathered at three laboratory test sites show AIM to be analytically consistent over the required range of particulate enumeration, and show that it detects 20% more abnormalities than by conventional microscopy, and with greater precision (CVs 5 to 20%). Complete urinalysis, including the microscopic examination, requires little more than 1 min for normal specimens, 3 min for most abnormal specimens. Actual throughput rate varies with the particulate composition of specimens; typically, it averages greater than 30 specimens per hour, a 300% improvement in urinalysis productivity by CAP standards and an almost 500% improvement when typical emergency-use demands are taken into account. PMID- 4028400 TI - Liquid-phase reactions started by rehydrating lyophilized reagents in a centrifugal analyzer. AB - In the disposable rotor of the SAM microcentrifugal analyzer, various lyophilized reagents are predistributed in 24 33-microL cuvets, for determination of multiple analytes in one specimen (e.g., for patient profiles). We evaluated a prototype of this system, which can be used at 25, 30, or 37 degrees C; absorbance readings at 340, 405, and 500 nm varied linearly up to 2.0 A. Starting the reactions by rehydrating the reagents with diluted serum is adequate because absorbance readings do not begin until 180 s after initiating the rehydration. Analytical performances of kinetic determinations at 30 degrees C showed good accuracy and correlation with other methods for creatine kinase, amylase, aspartate aminotransferase, and gamma-glutamyltransferase. Kinetic determinations for urea, and equilibrium determinations with blank corrections for glucose, cholesterol, and triglycerides gave excellent results for glucose and correct results for the other analytes. This compact analyzer combines the analytical performances of a centrifugal analyzer with the practicability of instruments having predistributed reagents. PMID- 4028401 TI - Use of chromatofocusing to detect a transferrin variant in serum of alcoholic subjects. AB - We describe a technique for detecting an abnormal (pl 5.7) transferrin component in serum, which appears after prolonged heavy consumption of alcohol. Serum transferrin was purified by chromatography on DEAE-Affi-Gel Blue and analyzed by chromatofocusing on an ion-exchange column (Mono P). The abnormal transferrin component was detected in 17 of 20 patients (85%) with a history or prolonged consumption of alcohol (100 g per day), and in control subjects who ingested up to 80 g of alcohol per day for seven days, but not in 14 normal control subjects or 14 patients with liver disease unrelated to alcohol. The variant consistently disappeared from the serum within three weeks of cessation of alcohol consumption. It is apparently produced by desialylation of ordinary human transferrin. We find that chromatofocusing on an ion-exchange column is a sensitive and reliable technique for its identification and conclude that detection of this desialylated transferrin indicates recent prolonged alcohol ingestion. PMID- 4028402 TI - Use of protein-based standards in automated colorimetric determinations of fructosamine in serum. AB - We have developed an automated colorimetric assay for glycated serum proteins (or fructosamines), measuring the reducing activity of serum in alkaline solution (pH 10.35) at 37 degrees C. The calibrants were prepared from a synthetic fructosamine (1-deoxy-1-morpholinofructose), although secondary standards of glycated bovine albumin were more robust in routine application. Interference was appreciable only with icteric specimens (bilirubin greater than 60 mumol/L), and between-batch imprecision (CV) was less than 2%. The range of fructosamine concentrations measured in 502 healthy (nondiabetic) blood donors was 1.87-2.87 mmol/L. There were no significant (p greater than 0.05) age- or sex-related differences in this population sample. Fructosamine accurately reflected blood glucose control as evidenced by the significant correlation with glucose concentrations in fasting plasma (r = 0.82, p less than 0.001) and with glycated hemoglobin (HbA1c) (r = 0.87, p less than 0.01) in 115 patients with type 2 (non insulin-dependent) diabetes mellitus. The test is simple and rapid to perform (75 samples per hour) and provides an alternative to HbA1c determinations for monitoring blood glucose control and assessing the effects of changes in diabetes management. PMID- 4028403 TI - Determinations of immunoglobulins G, A, and M in the Technicon RA-1000. AB - We evaluated the Technicon RA-1000 "Random Access" analyzer for the measurements of immunoglobulins G, A, and M in serum by turbidimetry. For various concentrations of serum pools the total CV ranged from 3.0 to 4.5% for IgG, from 3.1 to 3.2% for IgA, and from 4.8 to 5.4% for IgM. The linearity of the standard curves was good in the clinically useful ranges. Results for patients' samples correlated well with those determined with the Beckman Auto ICS (rate nephelometric method). Normal reference intervals (based on data for 200 healthy blood donors) are 7.67 to 16.87 g/L for IgG, 0.87 to 3.89 g/L for IgA, and 0.61 to 2.70 g/L for IgM. The RA-1000 requires only 8 microL for all three tests and can analyze 25 specimens for all three proteins in 37 min. Compared with other methods for immunoglobulin assays, the RA-1000 has higher throughput and offers significant savings in labor and reagent costs. PMID- 4028406 TI - Enzymatic correction of interference in the kinetic Jaffe reaction for determining creatinine in plasma. AB - We evaluated a simple, specific method for measuring plasma creatinine concentration, involving enzymatic degradation of creatinine before analysis by a kinetic Jaffe reaction. The enzymes--prepared in a dry, stable form--are convenient to use and eliminate the need to correct for sample dilution. As little as 50 microL of plasma is required, making the procedure ideal for use with samples from children. Between-day precision studies for determination of plasma creatinine at concentrations of 70 and 470 mumol/L yielded CVs of 7.8 and 4.3%, respectively. Analytical recovery of creatinine added to plasma samples ranged from 94 to 113%. Linear regression analysis demonstrated excellent agreement between results by this method and those by a "high performance" liquid chromatographic technique. PMID- 4028404 TI - Bedside micro-method for measuring effective hepatic blood flow, with use of first-order galactose clearance pharmacokinetics. AB - Data from first-order galactose clearance were used to estimate "effective" hepatic blood flow in normal subjects and in patients with hepatic diseases. Galactose clearance was determined by infusing galactose intravenously at a constant rate and measuring its resulting steady-state concentration in blood. The infusion rate must not exceed the maximum rate of galactose clearance by the liver, the "galactose elimination capacity." With this constraint and within the physiological and pathophysiological limits of hepatic blood flow, a constant infusion at 50 mg/min results in steady-state concentrations ranging from 20 to 200 mg/L. To measure galactose within this range, we modified a YSI Model 23A glucose analyzer and, using an immobilized galactose oxidase (EC 1.1.3.9)/hydrogen peroxide electrode system, accurately measured galactose in water and blood. The galactose metabolic clearance rate was calculated for six normal rats and for a normal and a cirrhotic human subject. The speed of the analysis (40 s), the small sample required (25 microL), and the suitability of fresh whole blood as the sample make the method ideal for measuring hepatic blood flow in small laboratory animals as well as for determining at bedside the effective hepatic blood flow in humans. PMID- 4028405 TI - Inaccurate values for direct bilirubin with some commonly used direct bilirubin procedures. AB - We compared five methods for the determination of total and direct bilirubins in serum samples from normal controls, subjects with Gilbert's syndrome, and serum pools containing about 50 and 150 mg of total bilirubin per liter. The Kodak Ektachem method and a diazotized sulfanilic acid method with 0.15 mmol/L sodium nitrite concentrations are the only methods that gave accurate direct bilirubin values, as judged by liquid-chromatographic results. The aca method that involved p-nitrobenzene diazonium tetrafluoroborate and another diazotized sulfanilic acid method with a higher concentration of sodium nitrite (0.8 mmol/L) yielded falsely high values for direct bilirubin, which could lead to clinical confusion. The more recently introduced diazotized sulfanilic acid method of the aca gave substantially better results than the p-nitrobenzene diazonium tetrafluoroborate method but was still inaccurate. Systematic investigation of these procedures revealed that the overestimation of direct bilirubin by the diazotized sulfanilic acid method was related to the amount of unconjugated bilirubin present and its ability to react as direct bilirubin in the presence of higher concentrations of sodium nitrite. Inherent properties of p-nitrobenzene diazonium tetrafluoroborate appeared to be responsible for inaccuracies in that method, which could not be corrected by varying reagent concentration or the reaction conditions. PMID- 4028407 TI - Hemoglobin interference from in vivo hemolysis. AB - Laboratory values for specimens from a case of intravascular hemolysis showed that hemoglobin was significantly increased and thus could interfere with the determination of other analytes. We studied this problem by adding increasing amounts of purified hemoglobin (to a maximum concentration of 19.3 mg/L) to aliquots of pooled serum samples. The hemoglobin significantly interfered with the determination of only five analytes: albumin, aspartate aminotransferase, direct bilirubin, and total protein on the SMAC, and creatinine on the Astra. We propose that for cases of proven intravascular hemolysis, values for only the analytes not affected by hemoglobin should be reported. We find lactate dehydrogenase activity useful in assessing the components of in vivo hemolysis; the differences between serum and plasma values for potassium, lactate dehydrogenase, and hemoglobin are related to in vitro hemolysis. Criteria for specimen collection and assessment of type of hemolysis are proposed. PMID- 4028408 TI - Mg2+ determined with a commercial kit and the Technicon RA 1000 analyzer. PMID- 4028409 TI - Severe depression of serum cholinesterase activity associated with two cases of hepatic encephalopathy. PMID- 4028410 TI - More efficient cyclosporin A assay. PMID- 4028411 TI - Relationship between arterial oxygen tension and serum aminotransferases in morbidly obese patients with fatty liver. PMID- 4028412 TI - Old and new aca methods for creatine kinase isoenzyme MB compared. PMID- 4028413 TI - Precise determination of 5-hydroxytryptamine in platelets and platelet-poor plasma. PMID- 4028414 TI - Inhibitory effect of ascorbic acid in oxalate assays involving oxalate decarboxylase. PMID- 4028415 TI - Positive interference with immunoassay of theophylline in serum of uremics. PMID- 4028416 TI - An automated method for measuring plasma citrate without protein precipitation. PMID- 4028417 TI - Stabilization of the reaction mixture used in urinary citrate estimations. PMID- 4028418 TI - Hepatotoxicity of prolonged methotrexate therapy for rheumatoid arthritis. PMID- 4028419 TI - Masked presentation of giant-cell arteritis. PMID- 4028420 TI - Streptobacillary fever. An unusual cause of infectious arthritis. PMID- 4028421 TI - Pregnancy and progressive systemic sclerosis. Case report and review of the literature. PMID- 4028422 TI - AIDS: current achievement, future problems. PMID- 4028423 TI - Evoked visual potentials. PMID- 4028424 TI - Visual potentials evoked by light-emitting diodes mounted in goggles. PMID- 4028425 TI - Contrast two-dimensional echocardiography in the diagnosis of adult congenital heart disease. PMID- 4028426 TI - The Cleveland Clinic Alcohol Rehabilitation Program: a treatment outcome study. A preliminary report. PMID- 4028427 TI - Chronic active hepatitis induced by nitrofurantoin. PMID- 4028428 TI - Squamous cell carcinoma of the rectal stump in a patient with ulcerative colitis. Report of a case and review of the literature. PMID- 4028429 TI - Osteomalacia associated with aluminum intoxication in a patient with chronic renal failure. PMID- 4028430 TI - Measurement of free choline concentrations in maternal and neonatal blood by micropyrolysis gas chromatography. AB - The development of a micropyrolysis gas chromatographic technique for the determination of free choline in plasma and erythrocytes is reported as a means to clinically assess choline status. A micropyrolyzer syringe unit was fabricated and the method was standardized through repeated trials with a single plasma specimen. The interassay coefficient of variance was 1.3% for the standardized trials on plasma and erythrocytes. Choline status was assessed in control women, mothers and premature infants at birth and up to 14 days of life. At birth, plasma choline levels in the infants (32.2 +/- 5.5 mumol/l) were significantly higher than those in the mothers (12.9 +/- 2.6 mumol/l) and the control women (16.9 +/- 1.6 mumol/l). The infant's plasma choline concentrations had decreased significantly by 7 days of life and remained at the lower level at day 14, independent of the nutritional intervention administered. PMID- 4028431 TI - Fluorometric measurement of glycosylated albumin in human serum. AB - A simple and rapid fluorometric assay of glycosylated albumin was developed using dansylated phenyl boronic acid (N-(5-dimethyl amino-1-naphthalene sulfonyl)-3 aminobenzene boronic acid). The emission spectrum of the reagent changes upon binding to cis-diols present on glycosylated albumin in serum, allowing quantitation of glycosylated albumin. Results from the new procedure correlated well with those from commercially prepared affinity chromatography (r = 0.85). PMID- 4028432 TI - A rapid flat gel isoelectric focusing method for the determination of apolipoprotein E phenotypes and its application. AB - A rapid flat gel isoelectric focusing method has been developed for the determination of apolipoprotein E phenotypes. Isoelectric focusing in 5% polyacrylamide flat gel with 8 mol/l urea and 2.8% pharmalyte (pH 4-6.5) was carried out at 3,000 V and 4 degrees C for 1 h under a constant power of 30 W. The separation of apolipoprotein E isoproteins was good and the isoelectric points were determined. Using this method, the apolipoprotein E phenotype frequency was examined in the Japanese population, and a higher frequency of phenotype E3/3 and a lower frequency of phenotype E3/2 were found in Japanese than those reported for the German, American or English population. In our focusing system the cut-off point of apolipoprotein E2/E3 ratio between the phenotype E3/3 and E3/2 was assumed to be approximately 0.9. These results indicate that this method may be useful for the determination of apolipoprotein E phenotypes. PMID- 4028433 TI - Plasma ferritin in old age. Influence of biological and pathological factors in a large elderly population. AB - The effects of biological (age, sex, weight) and pathological factors on plasma ferritin concentrations were documented in 776 unselected elderly patients aged 80.9 +/- 9.7 yr. A marked shift towards high values (159 +/- 142 micrograms/l) was observed in this elderly population together with the persistence of the well known sex-related difference in ferritin levels (higher levels in men). Twenty five percent of the population had high levels of ferritin (greater than or equal to 220 micrograms/l) but 75% of these high values (i.e. 18.5% of the population) could be readily explained by their known association with a particular pathology (inflammatory syndrome, renal failure, cardiovascular diseases, alcoholism). Only 6% of the population had unexplained high ferritin concentrations. Therefore, our data strongly suggest that the repeatedly reported increase of ferritin in the aged population is merely related to an age-associated pathology and may not be a normal physiological event occurring during the process of aging. PMID- 4028434 TI - Inhibition of A and B N-acetyl-beta-D-glucosaminidase urinary isoenzymes by urea. AB - A urinary fraction which inhibits the activity of N-acetyl-beta-D-glucosaminidase (NAG) has been isolated and identified as being urea. Usually present in high concentration, urea appears to be the only urinary component responsible for the frequently observed urinary NAG inhibition. The inhibition of the two urinary NAG isoenzymes A and B is competitive with respective Ki values of about 70 mmol/l and 60 mmol/l. With routine assay conditions, it seems that a dilution of urine prior to enzyme assay is sufficient to abolish the inhibition of the two isoenzymes A and B by endogenous urea. PMID- 4028435 TI - Serum aspartate and alanine aminotransferase in filariasis. AB - Serum aspartate aminotransferase level in filarial patients was estimated. The level was compared against the level of the same enzyme in non-filarial patients. Similarly estimated and compared was the level of serum alanine aminotransferase in the same groups of subjects. It was found that there was a mild but significant elevation of aspartate aminotransferase level above the normal level, in filarial patients in Nigeria. However, no concomitant elevation of alanine aminotransferase level was observed. PMID- 4028436 TI - New fluorometric assay of lysosomal acid lipase and its application to the diagnosis of Wolman and cholesteryl ester storage diseases. PMID- 4028437 TI - Extraction of lipids from human whole serum and lipoproteins and from rat liver tissue with methylene chloride-methanol: a comparison with extraction with chloroform-methanol. PMID- 4028438 TI - Enzymatic fluorometric method for the determination of D-arabinitol in serum by initial rate analysis. AB - We describe a new, simple, fluorometric assay for D-arabinitol in serum. The method is based on oxidation of D-arabinitol by D-arabinitol dehydrogenase (EC 1.1.1.11), with the concomitant reduction of NAD. The initial rate of NAD reduction, which is proportional to the D-arabinitol content of serum, can be measured with a recording spectrofluorometer. Sensitivity, specificity, recovery and reproducibility experiments gave satisfactory results. The proposed method is suitable for clinical use, and may be helpful in the diagnosis of invasive candidiasis. PMID- 4028439 TI - Erythrocyte and leukocyte lipids in alcoholic macrocytosis. AB - Erythrocytes and leukocytes were obtained from patients with alcoholic macrocytosis and their lipid composition compared with those from normal subjects. The patients had normal plasma cholesterol and fasting triglyceride levels with mild and fully compensated liver disease. There was no difference in the lipid composition of leukocytes from alcoholics compared with controls. Erythrocytes from patients with alcoholic macrocytosis had increased cholesterol content. The increased cholesterol content correlated with the MCV but there was no correlation between plasma and erythrocyte cholesterol. There was a decrease in erythrocyte phosphatidylethanolamine in alcoholic macrocytosis. There was no change in the fatty acid composition of the phospholipid fraction but there was an increase in the amount of linoleic acid in phosphatidylethanolamine. The double bond index, non-essential-to-essential fatty acid ratio and double bond index to saturated fatty acid ratio for the erythrocyte phospholipids were unchanged in alcoholic macrocytosis. Sodium dodecyl sulphate-polyacrylamide gel electrophoresis of erythrocyte membrane proteins from patients with alcoholic macrocytosis and control subjects showed no significant differences. PMID- 4028440 TI - Characterization of a serum factor interfering with the radioimmunoassay of prostatic acid phosphatase. AB - Storage of serum at temperatures above zero for short periods results in the spurious formation of a factor interfering with the radioimmunoassay of prostatic acid phosphatase. This factor acts by inhibiting the binding of radiolabelled tracer to the specific primary antiserum. The inhibiting factor is a protein of molecular mass 40 000 which is derived from an inactive high molecular mass precursor. Formation of the inhibiting factor is apparently reversible and its action can be neutralized by adding fresh serum to the incubation mixture. Serine protease inhibitors of synthetic or natural origin did not influence the activity of the inhibitor. Since incubations for long periods at temperatures above freezing are standard procedures in radioimmunoassays, formation of this inhibitor may occur in susceptible sera. It is suggested that problems with establishing specific assays for prostatic acid phosphatase may be explained by the generation of this inhibiting factor. PMID- 4028441 TI - Determination of urinary cortisol and 6 beta-hydroxycortisol by high performance liquid chromatography. AB - A method using high performance liquid chromatography for the quantitative determination of cortisol and 6 beta-hydroxycortisol in urine is described. Urine extracts were fractionated by high performance liquid chromatography. The peak of 6 beta-hydroxycortisol was identified on the basis of retention time (24.4 min) and its area was measured. The peak of cortisol could not be measured simultaneously with the same column because of interference by other absorbing materials. The cortisol and dexamethasone peaks were collected (Rt values 9.6 and 8.1 min, respectively), rechromatographed on another column system, and the concentration was determined. Precision and accuracy of the present method were within the range commonly achieved by other methods established for both steroids. Clinical utility of the present method was evaluated by measuring urinary cortisol and 6 beta-hydroxycortisol in normal subjects, in Cushing's syndrome and disease patients, and in patients receiving cortisol therapy. PMID- 4028442 TI - Automated stopped-flow analyser in clinical chemistry: determination of albumin with bromcresol green and purple. AB - We describe an adaptation of a microcomputer-controlled stopped-flow analyzer for automated analysis of albumin in serum. The immediate reaction between bromcresol green or purple and albumin is used to develop a routine procedure with 12 s reaction time. The approach shows excellent linearity to 68 g/l, good sensitivity, a relative SD of less than 0.5%, mean recovery 99.1%, high sample throughput (180 prediluted samples/h) and no significant interferences. The 'reaction time' related overestimation of albumin that appears in prolonged procedures is eliminated, and results with this method correlate well with those obtained using the more specific immunonephelometric method. PMID- 4028443 TI - Human erythrocyte histamine N-methyltransferase: radiochemical microassay and biochemical properties. AB - A radiochemical assay for the measurement of histamine N-methyltransferase (HNMT) activity in human erythrocytes (RBCs) has been developed. This assay was developed as a first step toward testing the hypothesis that the biochemical properties and regulation of HNMT in an easily obtainable human cell, the RBC, might reflect those of the enzyme in less accessible cells and tissues. The Michaelis (Km) constant in the RBC for histamine, the methyl acceptor substrate for the reaction, was 5.0 X 10(-5) mol/l. The Km constant for S-adenosyl-L methionine, the methyl donor, was 2.8 X 10(-6) mol/l. The assay was performed at a reaction pH of 7.4 with a potassium phosphate buffer. The product of the reaction was identified as N tau-methylhistamine by high performance liquid chromatography. The Kii for inhibition of the RBC enzyme by amodiaquine, an HNMT inhibitor, was 1.0 X 10(-7) mol/l, while the Kis value was 0.48 X 10(-7) mol/l. Blood samples obtained from 39 randomly selected adult white subjects had a mean activity of 130 +/- 30 U/ml of packed RBCs (mean +/- SD). Enzyme activities varied over a range from 74-213 U. There were no differences between men and women in mean activities, nor was there a significant correlation between RBC HNMT activity and age. The results of experiments in which lysates with 'low' and 'high' activities were mixed gave no indication that individual variations in RBC HNMT activities were due to the effects of endogenous enzyme inhibitors or activators. RBC HNMT activities measured in blood samples from 17 individual subjects four times over 6 wk were quite constant in each subject, with an average coefficient of variation of 6.2%. The availability of this assay will make it possible to test the hypothesis that individual variations in RBC HNMT activity might be used to predict individual differences in HNMT activity in other human cells and tissues. PMID- 4028444 TI - Reduced levels of plasma ascorbic acid (vitamin C) in sickle cell disease patients: its possible role in the oxidant damage to sickle cells in vivo. AB - The role of oxidant damage to red cells in sickle cell disease has been of interest in recent years. Ascorbic acid is a well known antioxidant. The present study found that sickle cell patients have low levels of plasma ascorbic acid. In addition, it was observed that the pretreatment of sickle cells with ascorbic acid protects their membranes against in vitro peroxidative lipid damage induced by their exposure to hydrogen peroxide. The data suggest that low plasma ascorbic acid levels in sickle cell patients may be a factor in the increased vulnerability of sickle cells to oxidant damage in vivo. PMID- 4028445 TI - An improved method for the determination of free and esterified carnitine. PMID- 4028446 TI - Direct radioimmunoassay for estriol 3-sulfate 16-glucuronide using specific antiserum without deconjugation. PMID- 4028447 TI - Polarographic quantification of salicylate in serum by salicylate hydroxylase. PMID- 4028448 TI - Frontal intermittent rhythmical delta activity and anterior bradyrhythmia. AB - Rhythmical intermittent delta activity was found in 162 patients (out of a total of 5,542 patients; i.e. 2.9%). The typical features of frontal rhythmical intermittent delta activity (FIRDA) were noted in 105 patients while in 43 the pattern of anterior bradyrhythmia (AB) was present. Mental decline with delirium or dementia was the most common clinical correlate in cases of FIRDA, whereas cerebrovascular disorder represented the by far most frequent etiology in cases of AB. The patient group with AB proved to be older than the population with FIRDA. Stress was laid on the distinctive EEG features of FIRDA and AB as well as their relationship to the level of vigilance. FIRDA invariably showed a maximum over the frontopolar region whereas AB was maximally developed either over frontopolar or over superior frontal areas. There is reason to presume that a superior frontal maximum is related to arousal mechanisms (with input into the supplementary motor zone). On the other hand, it is hypothesized that the frontopolar maximum of FIRDA reflects thought processes in a frontal lobe with compromised circulation. PMID- 4028449 TI - Features of the geriatric EEG: age-dependent incidence of POSTS. AB - Positive occipital sharp transients of sleep (POSTS) are well recognized as a normal electroencephalographic phenomenon in young to middle-aged persons, but little comment has been made concerning their occurrence in geriatric age groups. This study encompassing 365 electroencephalograms, showing POSTS among patients aged 22 to 86 years, demonstrates that the presence of POSTS is not an age limited occurrence, but extends over a wide age range into the later decades of life. Though the incidence of POSTS declined with advancing age, the diminution was not striking until after age 70. POSTS appeared only in normal and mildly abnormal EEGs. POSTS did not occur in markedly abnormal EEGs, and thus they resemble other features of normal sleep including sleep spindles and K-complexes. PMID- 4028450 TI - Reliability of rapid clinical staging of all night sleep EEG. AB - The recording of all night sleep EEGs on a portable cassette recorder, and the rapid visual staging of the sleep records at 20 times real time, represent innovations in sleep research methodology. The reliability of sleep stager percentages obtained in this way is examined in this article. In the first of two studies, all night sleep records for six individuals were each staged twice by each of two qualified electroencephalographers. Inter-rater and intra-rater reliability assessed by intraclass correlation methods was modest, requiring the averaging of results from two judges to reach acceptable levels. Following consistency training, the two electroencephalographers staged all night sleep records for six additional subjects. Acceptable reliability was achieved in measurement of stages 2, 3, 4 and REM, although difficulty in reliably distinguishing stage 1 from the awake stage persisted. On the basis of these results, rapidly paced visual interpretation of sleep records at 20 times real time is recommended as a feasible way of meeting demands imposed by innovations in the technology of recording sleep EEGs. PMID- 4028451 TI - EEG topography in porencephaly and arachnoid cyst. AB - With the topographic EEG mapping method, the correlation between the morphologic abnormality of the brain and its functional changes was investigated in 13 patients with porencephaly and arachnoid cyst verified by CT scan. The spatial distribution of the EEG activity was displayed in the delta, theta, alpha-1, alpha-2, beta-1, and beta-2 frequency bands. The abnormality of EEG topographic images (e.g., an increase of the power of delta activity and/or a decrease of the power of alpha activity in the involved side of the brain) was more marked in cases with porencephaly than those with arachnoid cyst, and in cases with mental retardation or paralysis than among those without. PMID- 4028452 TI - The EEG pattern in delirium tremens. PMID- 4028453 TI - Evoked potentials in non-convulsive status epilepticus. AB - To verify the results from previous studies, we performed EPs on 2 patients with nonconvulsive status epilepticus who demonstrated ictal behavioral changes and bilateral, often diffuse electrographic abnormalities. The EP modalities which were used, PVERs, BAERs, and SSERs, are highly reproducible in normal subjects. In contrast to previous findings, the ictal EPs were normal. Our results may indicate that, despite bilateral and frequently generalized ictal activity in some patients with nonconvulsive seizures, sensory processing at the brainstem and visual and somatosensory cortices remains preserved. PMID- 4028454 TI - Event-related potential in Alzheimer disease. AB - Auditory event - related potentials were studied in 20 patients with SDAT and 20 age and sex matched normal controls. Patients with SDAT showed prolonged latencies of N200 and P300 components. The mean amplitudes of N200 and P300 were lower in the SDAT group. This reflects the impairment of the speed of neural processing in patients with SDAT. There were no significant correlations of the progression of P300 latencies from mild to severe dementia according to global dementia scales. PMID- 4028455 TI - Mid-line epileptiform activity in adult electroencephalograms. AB - Nine cases among 1000 adults referred to our EEG Laboratory were found to have epileptiform discharges at the C-Z area, predominantly in the awake state. These were in the form of isolated spike and wave complexes in five cases (0.5%), and Mu-like rhythms in four (0.4%). In all cases, variable degrees of dementia were found, and the CT scan of the head revealed mild to moderate cerebral atrophy and ventricular enlargement, confirmed by quantitative measurement. It is postulated that diffuse cortical and subcortical structural alteration is a factor responsible for the genesis of mid-line epileptiform activity in adult EEG's. PMID- 4028456 TI - Dramatic and rapid shrinkage of a massive invasive prolactinoma with bromocriptine: a case report. AB - Shrinkage of a massive, highly invasive, longstanding (probably 40 years) prolactin-secreting pituitary tumour is described in which tumour volume was reduced by 40% 8 d after beginning bromocriptine treatment. After 4 months of treatment the tumour was only 11% of the pretreatment volume and by 8 months it was further reduced in size being confined to the pituitary fossa, which was partially empty. Reduction in tumour volume was accompanied by a gradual reduction in serum prolactin concentrations to normal values at 4 months. Between 4 and 18 months serum prolactin has remained normal on 5 mg of bromocriptine daily. Visual function improved within 48 h of starting bromocriptine and was almost normal by 6 d. CSF rhinorrhoea developed as the tumour shrank and was successfully managed with the relatively minor procedure of a diversionary lumbo peritoneal shunt. Bromocriptine should be considered as the initial treatment of choice for massive invasive prolactinomas because of the significant risk of morbidity from neurosurgical treatment. PMID- 4028457 TI - Hyperthyroidism and the impalpable thyroid gland. AB - A retrospective analysis of 594 unselected cases of hyperthyroidism from one district was made to determine whether the thyroid gland had been palpable on presentation. The thyroid had been diffusely palpable in 374 patients (63%), nodular in 110 (19%) and impalpable in 96 (16%); there was no clinical record in 14 (2%) cases. Under 40 years of age a diffuse gland was usual, being present in 86% of cases. The proportion of nodular and impalpable glands both increased progressively with age comprising 30% and 48% respectively in patients older than 70 years. Grave's ophthalmopathy was present in 13% of hyperthyroid patients with diffuse glands, in 12% of those with impalpable glands, but in only 1.5% of those with nodular thyroids. Thyroid autoantibodies were found with a similar frequency in all three groups. There was a very good correspondence between clinical assessment of shape and nodularity of thyroid and the results of isotope scanning; the majority of patients with impalpable glands (86%) had a diffuse uptake of isotope. In the elderly hyperthyroid patient an impalpable thyroid gland is common and is not a factor to weight against the diagnosis. PMID- 4028459 TI - Comparison of the clinical activity of mesulergine and pergolide in the treatment of hyperprolactinaemia. AB - The clinical activity of the new ergoline, mesulergine, was compared to pergolide in the treatment of hyperprolactinaemia. Mesulergine was given to 22 women and five men with hyperprolactinaemia. Serum prolactin was substantially lowered in 10 women; two subsequently conceived and completed normal pregnancies. Twelve women stopped treatment due to side-effects, usually nausea and vomiting, or inadequate responses. The side-effects were generally similar to those on bromocriptine; in one patient they were better and in four worse than on bromocriptine. The male patients were more tolerant of mesulergine, and substantial falls in serum prolactin were seen with evidence of tumour shrinkage. Twenty-seven women with hyperprolactinaemia received pergolide; serum prolactin was lowered or normalized in 16. Side-effects necessitating cessation of treatment were similar to those seen with bromocriptine. Nevertheless, four women tolerated pergolide better than bromocriptine and two women adequately treated with mesulergine had previously been intolerant of pergolide. We conclude that both pergolide and mesulergine may be useful and effective drugs in the treatment of hyperprolactinaemia as alternatives to bromocriptine. PMID- 4028458 TI - Influence of endogenous and exogenous oestrogens on posterior pituitary secretion in women. AB - Four normally menstruating subjects were studied throughout the menstrual cycle to investigate changes in plasma LH, arginine vasopressin (AVP), oxytocin (OT) and oxytocin associated neurophysin (NPOT). A clear mid-cycle LH peak was observed in each subject. Mean levels of AVP, OT and NPOT were 2.2 pmol/l, 1.1 pmol/l and 39 pmol/l, respectively. There were no significant differences between plasma levels during follicular, mid-cycle and luteal phases for each of these. Two further subjects with anovulatory cycles were studied in a similar way. In the first subject, with polycystic ovarian disease, posterior pituitary peptide levels were in the normal range, whereas the other subject, recovering from anorexia nervosa, had raised plasma levels of all posterior pituitary peptides (AVP 8.1 pmol/l, OT 1.8 pmol/l, NPOT 131 pmol/l, mean values) despite a normal osmolality. Administration of ethinyl oestradiol, 100 micrograms or 500 micrograms, had no effect of either AVP or OT, but 100 micrograms caused a marked rise in NPOT levels in all cases within 12 h (from mean 64 pmol/l to mean 196 pmol/l) and the levels remained elevated for 3 d. PMID- 4028460 TI - Computed tomography of the pituitary fossa in primary hypothyroidism. Effect of thyroxine treatment. AB - Computed tomography of the pituitary fossa was performed in 12 patients with primary hypothyroidism before and after thyroxine treatment. In three, herniation of the diaphragma sellae precluded accurate measurement of the density of the hypophysis. Eight of the remaining patients showed abnormally increased density of the pituitary gland after intravenous injection of contrast substance which was significantly correlated with the serum TSH-level (r = 0.913, P less than 0.001). After thyroxine treatment the intrasellar density decreased substantially in all but one. We suggest that the observed contrast enhancement reflects increased pituitary circulation associated with the augmented function of TSH producing cells in response to thyroid hormone deficiency. PMID- 4028461 TI - The effect of dopamine agonist therapy on large functionless pituitary tumours. AB - Fifteen patients (12 male) with large pituitary tumours and serum prolactin levels below 1000 mU/l were given dopamine agonist therapy (bromocriptine, mesulergine or pergolide) for a mean of 9 months (range 3-36 months). Serum prolactin became undetectable in all. Despite this, significant suprasellar extensions and any associated neurological defect remained in 14 patients, who therefore were referred for surgery. In one patient there was evidence of spontaneous pituitary infarction unrelated to dopamine agonist therapy. At operation 12 patients had apparently functionless pituitary adenomas which failed to immunostain for prolactin, one had an epidermoid cyst and one a Rathke's pouch cyst. We conclude that patients with large pituitary tumours and only a mildly elevated serum prolactin are unlikely to have prolactinomas, and that such tumours are not likely to show significant tumour shrinkage with medical treatment with dopamine agonists. PMID- 4028462 TI - Relationship between serum thyroglobulin and intrathyroidal stable iodine in human simple goitre. AB - Serum thyroglobulin levels are increased in many patients with simple goitre. This increase has been attributed to the release of thyroglobulin (Tg) from the colloid of necrosed follicles. To test the hypothesis that increased serum Tg could be related to the low intrathyroidal iodine concentration [I], the main cause of nontoxic goitre, these two variables were measured in 91 euthyroid goitrous patients and compared to serum free T3 and free T4 levels as well as thyroid weight. Thyroid iodine concentration was estimated from the X-ray fluorescence measurement of intrathyroidal iodine stores and from the weight of the gland estimated by planimetry. Serum Tg levels, the free T3/T4 ratio and thyroid weight were negatively correlated to [I] (Spearman's coefficient of correlation = - 0.44 (P = 0.001); -0.30 (P = 0.006); -0.33 (P = 0.001), respectively). Tg levels were also positively correlated to the T3/T4 ratio (R = 0.28, P = 0.008) and to the weight of the gland (R = 0.37; P = 0.001). These data suggest that, in simple goitre, increased serum Tg concentrations are partly related to the reduced concentration of iodine in goitre tissue (as are an increased T3/T4 ratio and the size of the goitre) and is not only the reflection of follicular necrosis. PMID- 4028463 TI - Sensory thresholds and motor responsiveness in thyroid disease: their responses to treatment and warming. AB - It has been our clinical observation that patients with hypothyroidism are relatively insensitive to the discomfort of venepuncture, whereas thyrotoxic patients seem to have a heightened sensitivity. In an initial study we have measured the sensory thresholds of perception along with motor responsiveness in hypothyroid, thyrotoxic and euthyroid subjects, employing a simple and readily reproducible technique. Sensory thresholds were elevated and motor responsiveness impaired in hypothyroid subjects as compared to euthyroid controls. In thyrotoxic subjects, motor responsiveness was significantly enhanced, but sensory thresholds did not differ from control values. In a subsequent study the threshold abnormalities of thyroid dysfunction were corrected by rendering the patients euthyroid with appropriate therapy. Warming a further group of untreated hypothyroid patients produced a similar improvement in motor responsiveness to that seen in the L-thyroxine-treated group, thus implying that this parameter is at least, in part, temperature dependent. Sensory thresholds would seem to be reliable reflectors of tissue thyroid status in hypothyroidism, whereas motor responsiveness seems the better guide to thyroid status across the whole spectrum of thyroid function. PMID- 4028464 TI - Urinary steroid metabolites in subjects with male pseudohermaphroditism due to 5 alpha-reductase deficiency. AB - To investigate the enzymatic basis for abnormal steroid metabolism in subjects with male pseudohermaphroditism due to 5 alpha-reductase deficiency, the ring A reduced urinary 5 beta and 5 alpha metabolites of testosterone, androstenedione, 11 beta-hydroxyandrostenedione, cortisol and corticosterone were measured by gas chromatography. Assays of the four pairs of urinary 5 beta and 5 alpha steroid metabolites revealed decreased conversion of the parent steroids to 5 alpha reduced urinary metabolites, with increased 5 beta to 5 alpha urinary steroid metabolite ratios. These studies establish that increased urinary 5 beta/5 alpha ratios are distinctive for this disorder, and represent the most reliable method for confirming the diagnosis of primary inherited 5 alpha-reductase deficiency. These data also suggest that the conversion on the many delta 4-3 ketosteroids to 5 alpha-reduced steroids may be due to a single enzyme with broad specificity, or multiple enzyme reductases with a common regulator. PMID- 4028465 TI - Single dose dexamethasone suppression test in children: dose relationship to body size. AB - We have performed an overnight single dose dexamethasone suppression test in 15 children at different dosages to determine the minimum dose required to suppress the 0800 h serum cortisol level. With a dexamethasone dose of 0.1 mg/m2 two of seven children showed suppression. When the dose was increased to 0.3 mg/m2 all of six patients showed suppression as did three given dexamethasone 0.5 mg/m2. We recommend that doses of dexamethasone should be calculated in terms of body surface area when assessing the hypothalamo-pituitary axis in children and that a dose of 0.3 mg/m2 should be used for suppression tests. PMID- 4028466 TI - Patients with an acoustic neurinoma examined with a tilting room. AB - Patients with acoustic neurinomas do not usually show vertigo or spontaneous nystagmus, suggesting a gradual decrease of vestibular function with adequate compensation. Seventeen patients with acoustic neurinoma were examined to test their postural control. Examination in the tilting room showed a visual dominance in postural control with these patients irrespective of involvement of the central vestibular system. The subjective horizon was determined in addition to routine audiovestibular examination, to be informed about the compensation process. When routine audiovestibular examination points to an acoustic neurinoma, a pathological subjective horizon favours the diagnosis, although this is not mandatory. The combination of tilting room and stabilometry is superior in detecting visual dominance to the standard Romberg test. PMID- 4028467 TI - Skin cover after petrosectomy. PMID- 4028468 TI - Oto-Rhino-Laryngological Research Society (ORS). Meeting, 5 October 1984. Abstracts. PMID- 4028469 TI - Surgery in congenital aural atresia. PMID- 4028470 TI - The evaluation of radiographs of the nasopharynx. AB - Radiographs of the nasopharynx are sometimes misinterpreted because of poor technical quality. A simple method of interpretation is suggested based upon measuring the airway immediately behind the upper part of the soft palate. If it is narrower than the width of the soft palate it is considered as markedly obstructed. When narrower than half of the soft palate, it is severely obstructed. When it is the same width as the soft palate, it is not narrowed. One hundred and forty radiographs were evaluated by this method and by previously described methods. All methods showed good correlation and the present method is easy to use and easy to teach and has proven to be useful even in radiographs which other methods fail to interpret. The importance of evaluating the airway instead of the adenoidal thickness is stressed. PMID- 4028471 TI - Reversibility of reduced mucociliary clearance in chronic sinusitis. AB - Nasal mucociliary clearance was measured before and after treatment in patients with chronic sinusitis. Nasal mucociliary transit time before the study was greater than 36 min in 8 out of 14 patients who were treated with S carboxymethylcysteine, and in 9 out of 22 patients who were treated by repeated antral lavage. The nasal mucociliary clearance was significantly improved by both treatment regimens. This may indicate that the malfunction of the nasal mucociliary system is not the cause of chronic sinusitis but an effect of chronic inflammation of the respiratory mucosa. PMID- 4028472 TI - The preservation of shoulder function after radical neck dissection. AB - The most disabling side effect of radical neck dissection is the 'shoulder syndrome', caused by denervation of the trapezius muscle. This is due to division of the spinal accessory nerve, the motor nerve to the trapezius. Using cadaver dissections the anatomy of the cervical spinal nerve supply to the trapezius has been studied. At radical neck dissection stimulation of these cervical spinal nerves produced contraction of the trapezius muscle. Thus a modified technique of radical dissection has been developed preserving the cervical spinal nerves to the trapezius. Comparison of patients undergoing this modified radical neck dissection with patients undergoing a classical radical neck dissection shows them to have better shoulder function. PMID- 4028473 TI - Fine needle aspiration cytology in the management of head and neck masses. AB - Fine needle aspiration cytology is a useful technique in the management of patients with masses in the head and neck, which is usually performed in co operation with a specialized cytopathologist. It has not until recently been an investigation used frequently by British otolaryngologists. This study shows that an aspiration cytology service may be run with the aid of a general histopathologist and demonstrates that it is a valuable aid to diagnosis even without the services of a specialized cytopathologist. PMID- 4028474 TI - Nasal Schneiderian papillomas: a study of 83 cases. AB - Nasal Schneiderian papillomas are unique lesions involving the mucosa of the nasal cavity and paranasal sinuses. Most often epidermoid in histological appearance, they favour 2 sites: the septum and the lateral wall of the nasal cavity. The medical literature on these tumours contains a plethora of contradictions concerning the nomenclature and no less than 54 separate designations are used. The synonyms are discussed and the term Schneiderian papilloma is proposed as the most suitable alternative. This study includes 83 patients with Schneiderian papillomas in whom the history, clinical and radiological findings, treatment procedures, pathological sections, recurrences, and associated malignancies were analyzed. Histological and clinical features were not helpful in predicting recurrence, but the recurrence rate was related to the treatment modalities; with 17% recurrences using an extranasal approach (lateral rhinotomy) and 59% using intranasal approach with limited excision. Schneiderian papillomas were associated with squamous cell carcinoma in 7 patients. Simultaneous papilloma and carcinoma were demonstrated in 4 patients at presentation (5%) and subsequently developing carcinoma in 3 patients (4%). As recurrences are frequent after inadequate removal and as association with maligancies may occur in both septal and lateral wall papillomas, radical aggressive surgery, thorough histological examination of the entire specimen, and careful follow-up are advocated. PMID- 4028475 TI - Inverted papillomas of the nose and the paranasal sinuses. AB - A series of 21 patients with inverted papillomas of the nose and/or the paranasal sinuses is presented. In 19 patients the tumour arose from the lateral nasal wall or paranasal sinuses, in 2 it arose from the nasal septum. Nine patients had been previously treated by nasal polypectomy. None of the patients with recurrences after primary surgical treatment showed any evidence of a progression from benign to malignant lesions. Only 14% of the patients suffered from recurrence, and it seems likely that this is because extensive surgical extirpation was recommended as primary treatment in most cases. We feel justified in recommending early and radical surgery. PMID- 4028477 TI - Invasive radiology. PMID- 4028476 TI - Resection of the interfrontal sinus septum in chronic or recurrent frontal sinusitis. Pre- and post-operative evaluation of the naso-frontal duct. AB - In 9 patients with recurrent attacks of acute or chronic frontal sinusitis, interfrontal sinus septum resection was performed. In 5 patients there was unilateral disease and in 4 bilateral. As all patients had previously had their frontal sinus trephined, pre- and post-operative naso-frontal duct function tests were performed. Pre-operatively, of 11 naso-frontal ducts tested (2 patients bilaterally) not one showed air flow on spontaneous respiration. Passage of air was obtained at forced inspiration and expiration in one patient and by Valsalva's manoeuvre in 6. No flow of air whatsoever was obtained in 4 of the ducts, whatever the method used. At follow-up performed 1-8 years post operatively 7 out of the 9 patients had no frontal sinus problems. The remaining 2 patients, who both had nasal allergy, were improved. Post-operative testing of the 9 patients showed flow of air on spontaneous respiration in 4 patients, whereas 4 needed forced inspiration or expiration and only one patient Valsalva's manoeuvre. The sinus septum resection, which is very simple to perform, is a good alternative to more extensive frontal sinus surgery but may be of less value in patients with nasal allergy. PMID- 4028478 TI - The pancreas. AB - A review has been made of the angiographic findings of different benign and malignant pancreatic lesions. The limited need for angiography as a diagnostic procedure is emphasized with guidelines to its indications when such other diagnostic modalities as US and CT are available. The technique, indications and results of pancreatic venography and venous sampling for hormone assay are discussed. PMID- 4028479 TI - Percutaneous transhepatic cholangiography. PMID- 4028480 TI - Percutaneous extraction of retained gallstones. PMID- 4028481 TI - Transjugular biopsy of the liver. AB - Percutaneous liver biopsy is the procedure of choice for most patients because of its simplicity and the high percentage of adequate biopsies obtained. It is a bedside procedure that does not require specialized equipment or the services of a highly trained angiographer. Nevertheless, complications are not uncommon unless strict contraindications are observed. It is usually recommended that patients be excluded who present with ascites, a prothrombin time less than 50%, a partial thromboplastin time greater than 10 s, or a platelet count less than 50 000. Mahal et al (1979) cite lack of attention to the contraindications as the most important factor in 22 bleeding episodes which occurred following 3800 percutaneous biopsies (0.7%). It is these contraindications that are the main indication for transjugular biopsy. Despite the highly selective nature of the patients who have undergone transjugular biopsy, the frequency of post-biopsy bleeding is only 0.35% and of death 0.13% (Table 1). These figures include the earliest experiences with this technique and can be expected to improve with increased experience and the development of new instruments that make the procedure safer and easier. Transjugular liver biopsy should be an essential procedure in every hospital that is involved in treating patients with liver disease. Unfortunately, although Lebrec et al (1982) estimated that approximately 30% of patients are rejected for percutaneous biopsy because of the presence of contraindications, relatively few centres have adopted this technique. This may be in part due to the reluctance of clinicians to subject their patients to a procedure they perceive as stressful, although a study by Poynard and Lebrec (1982) showed patients rated transjugular biopsy as less painful and inconvenient than percutaneous biopsy. PMID- 4028483 TI - Injuries to the talus. AB - The unique anatomic, functional, and vascular aspects of the talus predispose the area to difficulty in the management of its injuries. This article provides a practical guide to the treatment of fractures and dislocations of the talus. PMID- 4028482 TI - Digital fractures and dislocations. Diagnosis and treatment. AB - A detailed discussion of the often underestimated dilemma of digital fractures and dislocations is presented. Illustrations accentuate the important concepts. An aggressive attitude should be adopted to avoid mismanagement and prolonged convalescence. Should the need arise, surgical intervention is emphasized. PMID- 4028484 TI - Symposium on minimal incision surgery. PMID- 4028485 TI - Rationale for office-based foot surgery. AB - It is clear from this study that the majority of foot surgical cases being done in the United States may be performed in an office-based surgical setting when individual case considerations are made on a case-by-case basis. This entire study reflects the importance of physician preference relative to selecting a surgical environment for management of disorders and surgery of the foot. In some areas, a strong consensus of opinion existed concerning one surgical location or the other, but the overwhelming majority of responses indicated a case-by-case evaluation prior to physician selection of the surgical environment. The Delphi study was well validated by the survey of Alabama podiatrists in this regard. Traditionally, within the United States, the physician has acted as an agent to the patient and as an allocator of health care resources. Perhaps current concepts regarding patient hospitalization for certain surgical procedures would change if the physician were motivated (either intellectually or financially) toward office-based surgery on a individual case basis. Perhaps, in selected elective surgical procedures, patients could be sufficiently informed so that they could voice an opinion or preference relative to selection of the surgical environment. Additional research in this area is necessary. Expanded insight into established patterns of patient hospitalization practices and general anesthesia usage on these hospitalized patients may also be in order. Realizing full well the role of independent physician judgment in these matters, it may be that selection of general anesthesia and hospitalization for some elective surgery procedures reflects the physician's training rather than his appreciation of alternate routes for rendering reasonable and responsible care.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4028486 TI - Preoperative work-up and criteria. AB - No matter what the underlying podiatric problem, if surgical correction is considered, a good preoperative work-up is essential. This article deals with the preoperative work-up and criteria for a variety of ambulatory surgical procedures. PMID- 4028487 TI - Infections in minimal incision surgery. AB - We have attempted to delineate a logical and rational approach to the recognition and management of postoperative infections. The reader is urged to use the tenets presented strictly as guidelines. Each and every treatment regimen must be tailored to the individual case. The priorities of early detection and treatment as well as the routine ordering of Gram stain and culture and sensitivity studies must never be ignored. The best prevention of bone infection is high serum levels of antibiotic in the early stages of management. Also, medications should have a high osseous perfusion rate. Among these are the cephalosporins, oxacillins, cloxacillins, and penicillins. After making a definitive diagnosis of osteomyelitis, radiographic evidence may be anticipated from 21 days after the start of infection. Bone scans will demonstrate this condition much sooner and allow for earlier treatment. There are two basic requirements for effective antibiotic therapy. The antibiotic chosen must be capable of inhibiting the growth of the agent or agents causing the infection (this requires an identification of the infecting bacteria and the selection of an antibiotic effective against that organism). Secondly, a therapeutically effective concentration of the antibiotic must reach the infected tissues for a sufficient period of time to allow the antimicrobial activity of the compound to be effective. This requires a blood supply capable of delivering the antibiotic in the blood to the affected tissues. Furthermore, the physiologic state of the patient, the nutritional status, and the immunosuppressive systems should be supported by the means necessary to initiate host reactions against the invading organism. Three last principles may be added to this antibiotic prescribing regimen. (1) When using broad-spectrum antibiotics, be constantly aware of the likelihood of superinfection. This is the overgrowth of bacterial organisms present on the skin as normal flora that multiply rapidly when the surrounding flora is destroyed by the broad-spectrum antibiotic. (2) Ancillary measures including heat, elevation, and immobilization should be employed when conditions permit. (3) Always check for allergy before prescribing an antibiotic. There are no certainties in the treatment of infections; the regimens may change daily as newer and more effective medications are marketed. Nonetheless, the principles remain unchanged. Clinical disease results only when the invading agent evokes anatomic and functional damage in the course of obtaining the necessary requirements for survival.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 4028488 TI - Minimal incision closing base wedges. Transpositional axis rotation deformity correction. AB - The closing base wedge osteotomy will consistently yield excellent prognostic results when performed as described. The technique should be used when an angular change at the first metatarsal base is needed in any direction. PMID- 4028489 TI - Phalangeal set. AB - A summary of the phalangeal set procedure has been given with indications, significance of the correction, contraindications, biomechanical factors, operative procedure, and the acceptance in many podiatric and orthopedic surgery circles. This is an ambulatory procedure for toe deformities which allows for release of toe contractures, reduction of superimposition of phalanges, increased joint space, and correction of malalignment. PMID- 4028490 TI - Intramedullary decompression with condylectomy for intractable plantar keratoma. AB - A previously unreported method to relieve excessive plantargrade pressure which may create an intractable plantar keratoma associated with metatarsal head pain is presented. This method is referred to as an intramedullary metatarsal decompression with condylectomy and is performed through a dorsal minimum incision. The rotary action of the bur is demonstrated. This method has proved less traumatic than previous procedures, permitting immediate ambulation with little postoperative pain or edema. In a series of cases, I have compared this method with control studies on the same patient in which intramedullary metatarsal decompression was performed on one foot and a neck osteotomy on the opposite foot. Results with intramedullary metatarsal decompression have been comparable but have fewer postoperative sequelae. Exuberant bone callus formation dorsally and at the osteotomy site, lateral displacement of bone segments, frequency of transfer lesions, delayed healing or nonunion of the osteotomy site, and the possibility of synostosis when two adjacent bones were osteotomized are all decreased. A short review of the rationale, selection of cases, and criteria for orthotics is presented. The concept and simplified method of treatment applied in a series of cases is described. PMID- 4028491 TI - Early ambulation after minimal incision surgery for calcaneal spurs. AB - We feel that surgical intervention for heel spurs must be used with caution after a strong program of conservative measures is tried. We have learned that it is helpful to inform patients of the complexity of heel pain and that, even with surgery, their discomfort may continue for some time. We also have always advised patients that being overweight increases their pain. In light of this study, we will probably make stronger statements on the importance of losing excess weight. When people can maintain a desirable weight, heel spur syndrome surgery can produce uniformly good results. The key is in the careful selection of cases. PMID- 4028493 TI - The lixiscope. Use in examination and surgery. AB - The lixiscope is a portable, low-intensity fluoroscopic device, which provides convenience and safety for doctor and patient in examination and surgery. It gives a real time image which allows motion of the object to be observed and manipulation or surgical procedures to be performed under continuous visual monitoring. By changing lines of perspective, an appreciation of the object can be gained in three dimensions. This is especially important in visualizing geometry-dependent flaws, such as fractures, or in bringing out low-contrast objects from the background by relative motion. lixiscopic foot surgery is a new kind of foot surgery, opening up previous "closed" or minimal incision surgery. It has the benefits of the previous minimal incision surgery, with direct visualization of sophisticated procedures for consistent results. Future directions in this technology may include a lixiscope which will not require isotope replacement, true stereoscopic vision, and specialized devices for various branches of medicine. PMID- 4028492 TI - Ambulatory correction of hallux abducto valgus. Angulational, transpositional, derotation, and hallux set procedure. AB - The importance of correction of the high proximal articular set angle with a subluxed joint in hallux abducto valgus for long-term correction is cited. I have shown that if the laterally deviated facet is not corrected, pronatory forces continue to act on the first ray. When force is applied to a still laterally tilted first metatarsophalangeal joint, further side-slipping of the joint will occur even though modification of the Silver, McBride, or osteotomy procedures of the first metatarsal have been performed successfully. A review of the standard procedures for the correction of a high proximal set angle alone usually did not correct the high intermetatarsal angle usually associated with this problem. Combination procedures sometimes created complications. These include dorsal dislocation of the distal fragment in correction of the sagittal plane deformity causing metatarsalgia, limited dorsal range of motion, and damage to the sesamoids or sesamoid grooves on the plantar aspect of the first metatarsal. Angulational transpositional derotation and hallux set (ATDH) is offered to correct four deformities using one or two 1-cm incisions together with "stab" incisions. This method overcomes the many disadvantages of previous procedures and can be used in the presence of biomechanical pronatory forces to reduce the proximal articular set and intermetatarsal angles; to derotate the hallux; to neutralize the forces that pull the proximal phalanx off the first metatarsal head; and if necessary, to correct the sagittal plane deformity of the first metatarsal so that weight bearing is not disturbed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4028494 TI - Postsurgical complications and their clinical management. AB - Thus, we have briefly touched upon several sources of potential postsurgical complications. When these various conditions arise, they most often interfere with the overall healing process or total recovery period. In addition to causing aggravation and concern to the surgeon, they frequently complicate the operative impressions of the patient. The basic prevention techniques discussed should provide a substantial decrease in postsurgical complications. In summary, proper medical history and physical examination, vascular evaluation, biomechanical, radiographic, and laboratory studies are important. To employ good surgical preparation and sterile technique is also an important preventive measure. Plan your site of incision to maximize the approach to the bone correction while minimizing trauma to the underlying soft tissue structures. Always be prepared with adequate and back up instrumentation, including new surgical blades, burs, or Brophies. Use the instrumentation that best accomplishes the work proposed or contemplated. Good tissue handling and dissection along with adequate flushing of the wound site with sterile saline solutions are necessary. The well-informed patient can also reduce or prevent postoperative complications by the fact that they have been educated and informed about the pre-, intra-, and postoperative course of events. In conclusion, we have presented the most common postsurgical complications, their possible etiology, prevention, and management. Hopefully, these subjects will stimulate the practitioner to be more aware of such complications and therefore recognize and treat these less than desirable events appropriately. PMID- 4028495 TI - Prenatal diagnosis of cystic fibrosis by trehalase enzyme assay in amniotic fluid. AB - Amniocentesis and amniotic fluid trehalase enzyme assay were offered to 14 pregnant women at a 1 in 4 risk for a child with cystic fibrosis. Twelve of these pregnancies were screened at the 18th week of gestation; ten proceeded to term, seven following the finding of a normal trehalase activity and three despite the low enzyme level in amniotic fluid. In all ten cases prenatal diagnosis proved to be correct. In two cases with low enzyme activity parents opted for termination at the 19th week, and with PAS-Alcian Blue staining some slight histochemical lesions characteristic of cystic fibrosis were seen in the exocrine glands, including the pancreas and intestinal mucosa, of both fetuses. The total protein content in the meconium of these fetuses was significantly higher than in the controls. Results suggest that trehalase assay in the amniotic fluid is a potential prenatal test for cystic fibrosis and it appears that in fetuses with cystic fibrosis some histochemical and biochemical abnormalities can be observed as early as the 19th week of gestation. The role of ultrasound examination as an additional procedure for the prenatal diagnosis of cystic fibrosis is also discussed. PMID- 4028496 TI - Possible teratogenic effects of artificial insemination by donor. AB - Three trisomic offspring conceived by artificial insemination by donor (AID) were observed in a population in which a total of about 400 babies were so conceived. To test whether this excess represented a random fluctuation or a real effect of the AID procedure we surveyed, by questionnaire, a group of women who had born children conceived by AID. A significantly higher number of trisomic offspring were found than expected in a population with the observed age distribution. Further data are needed to test the validity of this observation. PMID- 4028497 TI - Metacarpophalangeal pattern profile analysis in Prader-Willi syndrome. A follow up report on 38 cases. AB - Metacarpophalangeal pattern profile (MCPP) was determined on 38 Prader-Willi syndrome individuals and compared with a previous report on 16 patients. Chromosome analysis showed an interstitial deletion of the long arm of chromosome 15 in 20 subjects and normal chromosome results in the remaining 18 individuals. The mean hand profile of 38 individuals was essentially flat while the profiles for the two groups based on chromosome findings were separate in the metacarpal area. Correlation studies confirmed the homogeneity of the deletion group relative to Prader-Willi syndrome individuals with normal chromosomes. Discriminant analysis of Prader-Willi syndrome versus control individuals produced a function of three MCPP variables plus age which may be applied as another diagnostic tool. PMID- 4028498 TI - Genetic linkage analysis of epidermolysis bullosa dystrophica, Cockayne-Touraine type. AB - Genetic linkage relationships between 27 informative marker loci and the locus for epidermolysis bullosa dystrophica, Cockayne-Touraine type (EBD-CT), were examined in a single large kindred. Linkage could not be demonstrated to any of the marker loci, further adding to the exclusion map for EBD-CT. The dominant forms of EBD so far delineated by clinical criteria and electron microscopy remain genetically undefined in terms of loci and allelism. Further investigation will be undertaken using restriction fragment length polymorphisms mapped to regions outside the existing exclusion map. PMID- 4028499 TI - Segregation analysis of a translocation (16;21)(p11;q22) in a large pedigree. AB - A large family with an inherited reciprocal translocation (16;21) is described. An unbalanced karyotype due to adjacent-1 segregation was documented in 6 cases, whereas 25 children dying within the first year of life and 4 individuals dying at later ages probably had the same abnormality. Therefore minimal and maximal risk estimates were calculated to be 6.0% and 26.5% for female, respectively, 4.8% and 33.3% for male translocation heterozygotes. Among the karyotyped phenotypically normal offspring of male as well as female carriers the ratio of normal children to balanced carriers was not different from 1:1. PMID- 4028501 TI - The characteristic physiognomy and tissue specific karyotype distribution in the Pallister-Killian syndrome. AB - We report a child with clinical features remarkably similar to those of our patient reported as tetrasomy 21 in 1982. Improved banding in this, and the previous case, together with gene dosage studies, and subsequent reports in the literature lead us to conclude that these patients are in fact tetrasomic for 12p. The clinical features of these children are most distinctive and the importance of their recognition lies in the fact that the abnormal cell line is virtually confined to fibroblast studies. PMID- 4028500 TI - Autosomal dominant cataract and microcornea associated with myopia in a Sicilian family. AB - A Sicilian family is reported in which 36 individuals, in 5 successive generations, were affected with congenital cataracts, microcornea and myopia with an autosomal pattern of inheritance. PMID- 4028502 TI - The facio-audio-symphalangism syndrome: report of a case and review of the literature. AB - A detailed account is given of a 5-year-old girl with the facio-audio symphalangism syndrome. This genetic disorder has been known previously by other names, including the WL syndrome. The reasons for suggesting this new descriptive term are given, along with a review of the literature. PMID- 4028503 TI - The ocular form of osteogenesis imperfecta: a new autosomal recessive syndrome. AB - We have investigated a South African family of Indian stock in which 4 brothers and 2 cousins had a severe form of osteogenesis imperfecta (OI) together with blindness due to hyperplasia of the vitreous, corneal opacity and secondary glaucoma. To the best of our knowledge the syndromic association of OI and ocular problems of this type has not previously been reported, and we believe that this condition is a newly recognised entity. The pedigree is consistent with autosomal recessive inheritance. PMID- 4028504 TI - The Groll-Hirschowitz syndrome. AB - Two sisters showed a similar disorder with cachexia, sensory deafness, and upper gastrointestinal abnormalities. The family pedigree suggests autosomal recessive inheritance of the disorder. Demyelinization demonstrated by a peripheral nerve biopsy may explain the basis for the manifestations. Only one family with this unique syndrome has been reported in the literature. The term "The Groll Hirschowitz Syndrome" has been suggested, named after the two physicians who first described this condition. PMID- 4028505 TI - Yq deletion (q11.21) in a H-Y+ azoospermic male. AB - A large deletion of the long arm (q11.21) of chromosome Y without mosaicism was found in a 28-year-old male. The proband has a normal height and normal male habitus but with azoospermia. The occurrence of H-Y+ level, azoospermia and loss of a great portion of euchromatic Yq in the proband is analyzed. PMID- 4028506 TI - Monosomy 16q: a distinct syndrome. Apropos of a de novo del(16) (q2100q2300). AB - A 2-month-old boy with delayed growth and development, brachycephaly, large anterior fontanelle, low-set folded ears, micrognathia, aortic coarctation, floppy abdominal muscles, and pes varus, was found to have a 46,XY,del(16)(q2100q2300) de novo karyotype. This observation corroborates both the distinctness of the 16q monosomy syndrome and the pathogenetic role of the band 16q21. PMID- 4028507 TI - Fra (X) syndrome and autism. PMID- 4028508 TI - Fragile sites and chromosome breakpoints in constitutional rearrangements. PMID- 4028509 TI - Detection of fragile sites on human chromosomes. PMID- 4028510 TI - Proceedings of the High Blood Pressure Research Council of Australia. 6th meeting. Sydney, December 1984. PMID- 4028511 TI - Migration-induced changes in blood pressure: a controlled longitudinal study. AB - A longitudinal study of the effects of migration on blood pressure and related factors is being carried out in members of a black Kenyan population who migrate from a traditional rural community to an urban environment. Data on the first 139 migrants (78 male, 61 female) and 204 control non-migrants (126 male, 78 female) who have been followed up for a period of 6 months are presented. Blood pressure changes rapidly on migration (within the first 2 months); thereafter trends between migrants and controls differ. Significant differences in systolic pressure between migrants and controls are found at all examinations during the 6 month follow-up in both sexes. Diastolic pressure falls in controls but rises in migrants, the greatest difference being seen at the 6 month examination. Migration is associated with a marked increase in dietary sodium and a fall in potassium demonstrated by measurements of urinary electrolyte excretion in 3 X 12 h or 3 X 24 h urine collections. Analysis of covariance shows that the blood pressure differences between migrants and controls are partly explained by urinary sodium/potassium ratios and in some instances by body weight. PMID- 4028513 TI - Increased renal prostanoid synthesis after unclipping the one-kidney, one-clip hypertensive rat: effect of renal denervation. AB - Renal denervation of hypertensive one-kidney, one-clip (1K, 1C) rats resulted in a minor fall in blood pressure (216, s.e.m. = 4, to 182, s.e.m. = 4, mmHg) 24 h later, which returned to predenervation levels with 1 week. Subsequent unclipping led to a similar fall in blood pressure in denervated (202, s.e.m. = 4 to 142, s.e.m. = 3) and sham-denervated (211, s.e.m. = 5 to 147, s.e.m. = 4) rats. Unclipping also resulted in a marked rise in urinary PGE2 and 6-keto PFG1 alpha in both denervated and sham-denervated animals. It appears that 1K, 1C hypertension, 8 weeks after clipping, is only slightly dependent on renal nerves. Unclipping results in increased renal synthesis of PGE2 and PGI2 which is not dependent on intact renal innervation. PMID- 4028512 TI - Blood pressure, salt taste and sodium excretion in rats exposed prenatally to high salt diet. AB - Blood pressure, sodium excretion and salt taste were examined in Sprague Dawley (SD) and Munich Wistar (MW) rats exposed prenatally to either a high salt (2.3% NaCl w/w) or control diet. There was no significant difference in blood pressure at 2, 6 or 12 months between high salt and control groups in either strain. Similarly there was no significant difference in sodium excretion following a saline load by gavage (150 mmol/l, 1.5% BW). Munich Wistar rats which received high salt diet prenatally exhibited a reduced saline preference when offered a choice between water and 150 mmol/l NaCl as drinking fluid. There was no significant difference in saline preference between Sprague Dawley rats which received the high salt or control diet. Prenatal exposure to high salt diet failed to alter the blood pressure or excretion of a salt load in either SD or MW rats. In MW rats but not SD high salt diet prenatally resulted in a reduced saline preference at 3 months of age. PMID- 4028514 TI - A randomized controlled trial of the effect of alcohol consumption on blood pressure. AB - Forty-six healthy normotensive male drinkers participated in a randomized, controlled, crossover trial to study the effects of varying alcohol intake on blood pressure. Alcohol consumption (calculated from weekly diaries) was reduced from 336.3 (s.e.m. = 20.2) to 64.5 (s.e.m. = 5.6) ml ethanol/week by drinking low alcohol content beer alone. Systolic blood pressure fell significantly during reduction of alcohol intake and rose again when normal drinking habits were resumed, the mean difference during the last 2 weeks of normal or low alcohol intake being 3.8 mmHg. This effect of alcohol on blood pressure was independent of a small but significant decrease in weight following reduction of alcohol intake. The change in blood pressure correlated with change in alcohol consumption (r = 0.53, P less than 0.001) with a 1 mmHg fall predicted for each 100 ml of reduction in ethanol intake/week. We conclude that regular moderate alcohol consumption has a direct (but reversible) pressor effect in normotensive men. PMID- 4028515 TI - Increased plasma noradrenaline during low dose adrenaline infusion in resting man and during sympathetic stimulation. AB - Both resting and stimulated (straight-leg raising and head-up tilt) levels of arterial and venous plasma noradrenaline were significantly higher during low dose adrenaline infusion in five mild hypertensive and four normotensive patients with one adrenal. Repeat adrenaline infusions in the five hypertensive patients while measuring noradrenaline clearance (3H-noradrenaline constant infusion) achieved similar levels of plasma adrenaline, and similar increases in plasma noradrenaline, within five min of achieving target infusion rate. Increased plasma noradrenaline was not explained by reduced clearance. These results are consistent with the hypothesis that physiological concentrations of adrenaline are capable of facilitating noradrenaline release in man. PMID- 4028516 TI - Acute haemodynamic responses to unilateral renal artery stenosis in conscious dogs. AB - The acute responses to renal artery stenosis were studied in chronically instrumented, unanaesthetized dogs. Stenosis of one renal artery produced a rise in arterial pressure and a fall in total peripheral conductance, but no change in cardiac output. The resistance to blood flow of the stenotic kidney 1 h after stenosis was 25% greater than before stenosis. This rise in resistance was due to the resistance of the renal artery stenosis itself. Blood flow to the contralateral kidney fell by 13% (s.e.m. = 3) at 1 h and resistance rose by 39% (s.e.m. = 5). Plasma renin activity was elevated approximately 10 fold. Calculations of changes in peripheral conductances following stenosis showed that the stenotic kidney was responsible for 14% of the fall in total peripheral conductance at 1 h, and the contralateral kidney for 18%. Thus acute renal artery stenosis produced a prompt rise in arterial pressure due to reduced peripheral conductance, of which the two kidneys (stenotic and contralateral) were responsible for one-third. PMID- 4028517 TI - Effect of magnesium on passive fluxes of lithium in the human erythrocyte. AB - Extracellular Mg2+ is known to inhibit the passive Na+ and K+ fluxes in the human erythrocyte. In this study the effect of extracellular Mg2+ on Li+ efflux was measured in erythrocytes from 29 normotensive and essential hypertensive subjects. Magnesium produced a variable inhibition of between 0 and 47% in Li+ efflux in different subjects and this effect was unrelated to initial cell Li+, blood pressure or to an action on the co- or counter-transport pathways for this cation. A positive correlation was observed between the magnitude of the passive Li+ efflux and its inhibition (0 to 47%) by Mg2+ ions. Thus Mg2+ has an inhibitory effect on passive Li+ permeability which is unrelated to essential hypertension. PMID- 4028518 TI - Total body sodium in immature spontaneously hypertensive and Wistar Kyoto rats. AB - Total body sodium of male and female spontaneously hypertensive (SHR) and Wistar Kyoto (WKY) rats was estimated weekly during the first 8 weeks of life by measuring exchangeable sodium (ENa). Blood pressure and sodium intake was measured from weeks 4 to 8. SHR had significantly higher blood pressure and sodium intake than WKY from 4 to 8 weeks of age. ENa was higher in SHR than WKY throughout the first 8 weeks of life. Relative sodium retention was observed in SHR during weeks 5 to 8 despite a significant rise in SHR blood pressure and fall in sodium intake. These findings suggest a change in the renal pressure/natriuresis relationship at this age in the SHR. PMID- 4028520 TI - Blood pressure responses to dietary sodium manipulation during normotensive human pregnancy. AB - Short-term salt loading and salt restriction in a group of normal pregnant women produced no changes in lying, sitting or standing blood pressures or heart rates. Home blood pressures showed no trend to change over the periods of altered salt intake. Although plasma volume and plasma renin activity changed with altered salt intake, there were no relationships between changes in these parameters and changes in mean arterial pressures (MAP) between the low and high salt diets. Capillary permeability and echocardiographic dimensions were unchanged by salt intake once sodium balance had been established. PMID- 4028519 TI - In vitro calcium dependence of arterial smooth muscle in human hypertension. AB - Digital arteries, removed at autopsy from 12 hypertensives and 11 normotensives, have been compared in vitro for the calcium dependence of contractures produced by potassium chloride and noradrenaline, and the potency of verapamil to antagonize contractures to noradrenaline. No significant differences were found between the vessels from the hypertensives and normotensives for the pD2 values or the maximum response to either potassium chloride or noradrenaline in bathing solutions containing 2.5, 1.0, 0.5 or 0 mmol/l calcium chloride. There were also no significant differences between the vessels, from the hypertensive or normotensives, in the pD2 values for the addition of calcium chloride to arteries exposed to potassium chloride or noradrenaline in a calcium free bathing medium, in the ability of verapamil to shift the pD2 values for noradrenaline, nor in the ability of verapamil to reduce the maximum responses to noradrenaline (except at the two highest concentrations of verapamil tested). It is concluded that it is unlikely to be a primary abnormality of the mechanisms regulating calcium ion entry and release in vascular smooth muscle in human hypertension. PMID- 4028521 TI - Immunoferritin electron microscopic studies with antibasophil serum of guinea pig basophil degranulation and regranulation in vitro. AB - We have previously shown that degranulated guinea pig basophils in vitro do not die. Rather, they recover, and these mature cells rebuild granules in the absence of nuclear changes of immaturity or of mitoses. This ability to survive the explosive release of cytoplasmic granules and to rebuild granules was the first such demonstration for a mature granulocyte. We utilized this model of antigen induced basophil degranulation and recovery in vitro, in conjunction with a specific antibasophil serum (ABS) and indirect immunoferritin electron microscopy, in order to localize the anatomic sites of expression of the antigen(s) recognizing ABS during the secretory and recovery events. Basophil surface membranes were labeled prior to degranulation, during degranulation, after degranulation, and as mature, polynuclear, granule-free cells began to rebuild new granules. In addition, the plasma membranes of non-granule containing, glycogen positive, small mononuclear cells were labeled. These were few in number and were thought to be precursor cells in the basophil lineage. Controls, either nondegranulated basophils at a variety of culture intervals, or basophils following degranulation and during recovery, were done using normal rabbit serum (NRS) and an indirect immunoferritin electron microscopic technique. These were all negative. Moreover, contaminating eosinophils, neutrophils, and lymphocytes were also negative. Extruded granules were labeled with ferritin (ABS) on their membrane-free, finely granular exteriors, but not within the lamellar array of their matrixes. Extruded granules were not labeled in control experiments. When tested with ABS, membrane-bound granules in the cytoplasm prior to release and membrane-free, released granules contained within degranulation sacs, were negative, as was the membrane of sacs. Immature, membrane-bound granules were also negative. Ferritin binding to membranes was seen in narrow channels, vesicles, and larger vacuoles, as well as in multivesicular bodies, present in the peripheral cytoplasm. This distribution of labeled sites was not observed in neutrophils, eosinophils, and lymphocytes which were also routinely present in these preparations. These sites were not labeled in basophils or other cells in control studies using ferritin and NRS. This indicates the necessity for specific binding to basophils in order to visualize this process. Whether most such sites represent residual endocytosis at 4 degrees C or binding to open invaginations near surfaces of cells does not detract from their specificity and thus expression of specific antigen(s)-binding sites in basophils. PMID- 4028522 TI - Covalent binding of [35S]cysteine to the labile binding site of the third component of complement: a physiological approach. AB - The alternative pathway of complement was activated physiologically by agarose beads to which [35S]cysteine had been bound by a disulfide link. The activated form of the third component of complement, C3b, which had bound to the radioactive cysteine was then released from the agarose bead with dithiothreitol. The [35S]cysteine was shown to be covalently bound to the alpha' chain of C3b, and to its known major breakdown product, the 66,000-Da polypeptide. This is highly suggestive that complement activation has led to formation of a peptide bond between the radioactive cysteine and the labile binding site on the alpha' chain of C3b. This radioactive marker will enable the amino acid sequence of the labile binding site to be determined, with the knowledge that the labeling of the amino acid(s) has occurred during physiological activation. PMID- 4028523 TI - Renal prognosis in women with hereditary nephritis. AB - Renal prognosis cannot be easily predicted in females with hereditary nephritis (HN). Thirty-six women with persistent urinary abnormalities, belonging to 24 families with progressive HN, were studied. Renal biopsy specimens were available in 23 patients and were studied by light and electron microscopy (EM). Nine women (group I) progressed to early renal failure, at 35 yrs of age or less. Five women (group II) progressed to late renal failure at 45 yrs of age or more. In contrast, 22 patients have so far normal renal function, and 14 of these (group IV) range from 31 to 62 yrs of age. Diffuse glomerular basement membrane (GBM) thickening was found by EM in 6 of 7 cases of group I, whereas it was found in no patient of group IV. The following features are suggestive of progressive nephritis in females: gross hematuria in childhood, nephrotic syndrome, and diffuse GBM thickening by EM. In contrast, family history of HN without nerve deafness, normal or nearly normal kidney on repeat biopsy, and thin or normal GBM by EM are suggestive of less or nonprogressive renal disease. Further follow-up is needed to assess the prognostic significance of these features. PMID- 4028524 TI - Children with chronic renal failure in the Federal Republic of Germany: II. Primary renal diseases, age and intervals from early renal failure to renal death. Arbeitsgemeinschaft fur Padiatrische Nephrologie. AB - In a retrospective survey, 623 children with chronic renal failure (CRF) comprising a 7-year period were registered in the Federal Republic of Germany. The primary renal disease could be classified in 91% of the patients. Pyelonephritis was the most frequent diagnosis (31%), followed by glomerulopathies (20%), renal hypoplasia or dysplasia (14%), cystic kidney disease including nephronophthisis (12%), other hereditary nephropathies (7%), and vascular nephropathies (4%). At the time of first presentation, 23% of the children with preterminal chronic renal failure were younger than 5 years, 34% 5 to 10 years and 43% 10 to 16 years old. At the time of renal death, the serum creatinine level was below 10 mg/dl in 84% of the children below 5 years, compared to 5% in the patients older than 10 years. The mean interval from the first presentation of CRF to the terminal stage was 6 months in vascular nephropathies, 19 months in cystic renal disease, 26 months in glomerular disorders, 32 months in pyelonephritis, and 36 months in hereditary nephropathies and in renal hypoplasia or dysplasia. The range of these intervals is so large, even when diagnostic subgroups are considered, that a reliable prediction of the individual course from the underlying kidney disease is not possible. PMID- 4028525 TI - Pruritus and mast cell proliferation of the skin in end stage renal failure. AB - We studied the relationships between dermal mast cell proliferation and pruritus or hyperparathyroidism in hemodialysis (HD). Skin biopsies were taken from 59 patients in end stage renal failure; 51 were on maintenance HD, and the other 8 were not. As a control, 34 non-renal failure pruritic patients were used. Thirty one of the 59 end stage renal failure patients (52.5%) had pruritus. The incidences of pruritus found in patients on HD and those not on HD were 56.9% and 25%, respectively. Significantly larger numbers of dermal mast cells were found in HD patients than in the control. There was no clear relationship between dermal mast cell proliferation and serum parathyroid hormone (PTH) levels. We speculated that the cause of pruritus in the patients undergoing maintenance HD was due to an increase of dermal mast cells and a release of histamine as a result of extra-corporeal circulation. PMID- 4028526 TI - Post-heparin lipolytic activity in acute renal failure. AB - Total post-heparin lipolytic activity (PHLA), hepatic triglyceride lipase (HTGL) and protamine inactivated lipoprotein lipase (LPL) and plasma lipoprotein pattern were investigated in 8 patients with acute renal failure (ARF). PHLA was determined at 5, 10, 15, 30, 45 and 60 minutes after heparin administration (100 U/kg b.w.). Maximal PHLA in ARF was 6.12 +/- 1.56 mumol FFA/ml/h at 10 minutes versus 14.62 +/- 4.29 at 45 min in controls (= 42%, p less than 0.001). PHLA was reduced in ARF throughout the study period (p less than 0.001). Maximal HTGL activity (3.06 +/- 0.84 mumol FFA/ml/h) was obtained at 10 min in ARF versus 8.97 +/- 3.11 after 15 min in controls (= 34%, p less than 0.001). HTGL in ARF differed from controls at all points of determination (p less than 0.001). LPL maximum was 3.12 +/- 1.93 mumol FFA/ml/h at 15 min in ARF and 7.65 +/- 3.44 at 45 min in controls (= 40%, p less than 0.001). LPL activity was different from controls at 30, 45 and 60 min (p less than 0.001) but not at 5, 10 and 15 min after heparin injection. Due to a rapid decrease of LPL activity (half maximal activity after 34 min in ARF versus 94 min in controls, p less than 0.05) activity half life of PHLA was diminished in ARF (49 min in ARF versus 112 min in controls, p less than 0.01). Thus both the activity of HTGL and LPL is impaired in ARF. Because of the different activation kinetics of the two PHLA fractions no conclusions concerning maximal enzyme activities can be drawn from single determinations as suggested in previous studies on chronic renal failure. PMID- 4028527 TI - Possible mechanisms of hydrocarbon-associated glomerulonephritis. AB - Many hydrocarbons have properties which make them candidates for causing glomerulonephritis. They alter most immune functions and create a state of immunity deficiency; they damage the tubules which may lead to interstitial fibrosis and increased postglomerular capillary resistance furthering the trapping of macromolecules in the glomeruli; and they probably increase tissue permeability to macromolecules. The idea that hydrocarbons cause glomerulonephritis is supported by findings of an association between glomerulonephritis and hydrocarbon exposure, by findings of a relationship between tubulointerstitial damage and glomerular filtration rate in glomerulonephritis, and by findings of immunity deficiency in most subgroups of glomerulonephritis. PMID- 4028528 TI - Response of plasma vasopressin to changes in extracellular volume and/or plasma osmolality in patients on maintenance hemodialysis. AB - The effect of changes in extracellular volume versus changes in plasma osmolality on arginine vasopressin (AVP) release was studied in 6 patients with terminal renal failure maintained on chronic hemodialysis. The day of the study, the patients were treated by sequential ultrafiltration lasting 1 hour followed by a 3-hour conventional hemodialysis session. The ultrafiltration resulted in the removal of 460 to 1,170 ml (mean = 860 ml) of volume. Body weight during the combined procedures fell by 1.6 +/- 0.4 kg (mean +/- s.e.m.) while mean arterial pressure decreased only slightly. Plasma osmolality was unaffected by sequential ultrafiltration, but decreased from 313 +/- 4 mosm/kg H2O to 291 +/- 4 mosm/kg H2O during hemodialysis. Initial plasma AVP concentration was high at 4.45 +/- 0.25 pg/ml and remained unchanged during the sequential ultrafiltration at 4.55 +/- 0.37 pg/ml, but it fell during the hemodialysis to 2.47 +/- 0.45 pg/ml. A hypotensive episode observed in one patient towards the end of hemodialysis resulted in a sharp increase in plasma AVP concentration from 5.5 to 18 pg/ml. During the combined procedures, plasma AVP and plasma osmolality showed a close and linear correlation (r = 0.63, n = 23, p less than 0.001). These findings suggest that in patients on maintenance hemodialysis, changes in plasma osmolality play a predominant role in determining AVP secretion whereas a marked decrease in volume without ensuing hypotension has no effect on AVP release. PMID- 4028529 TI - Intramuscular iron replenishment and replacement combined with testosterone enanthate in maintenance hemodialysis anemia: a follow-up of up to 8 years on 16 patients. AB - Sixteen chronic uremics who showed exhausted bone marrow iron stores and mean hematocrit values of 20.9 +/- 4.2% at the time of starting maintenance hemodialysis (HD) were treated by means of intramuscular iron dextran (IMD) (400 mg/month) for six months. By the end of this replenishment period, stainable bone marrow iron was observed and mean hematocrit values increased to 27.2 +/- 4.9% (p greater than 0.001). At this time, 200 mg of IMD/month and testosterone enanthate (1.5 g/month) were prescribed for the whole follow-up period (up to 8 years). The observed mean hematocrit values were up to 46.1 +/- 1.6%. Major side effects were not observed. The process of slow iron reabsorption from the intramuscular injection site (up to 4 weeks) also implies the splitting of iron from dextran, therefore preventing bone marrow deposits of iron dextran complexes which make iron unavailable for erythropoiesis. High doses of testosterone enanthate can normalize hematocrit values of maintenance hemodialysis patients with replenished bone marrow iron stores. PMID- 4028530 TI - Cardial decompensation caused by hypertension and polyglobulia associated with multiple renal oncocytomas. AB - A 43 year old man was referred to the Internal Department for the examination of cardial decompensation, hypertension, polyglobulia and atrophy blanche of the lower legs. Clinical and supersonic examination revealed two tumors in the left kidney (diameter 8 and 3.5 cm) and some small tumors in the right kidney. Laboratory studies disclosed erythropoietin levels up to 170 mU/ml (standard 14 61 mU/ml) and a red blood cell count of up to 8 X 10(6)/ml. After recompensation, a radical left nephrectomy and the removal of three small tumors of the right kidney four weeks later was initiated. Postoperative erythropoietin levels and red blood cell count sank to the normal range leading to the reduction of antihypertensive therapy. The clinical course indicates a strong etiological connection between hypertension as well as polyglobulia with the multiple bilateral oncocytomas. Polycythemia also led to the atrophy blanche which had resulted from disturbances of microcirculation. PMID- 4028531 TI - Crystalluria following aminopenicillin therapy. PMID- 4028532 TI - Nifedipine in hemodialyzed patients. PMID- 4028533 TI - Abdominal pseudocyst; the cause of repeated peritonitis during continuous ambulatory peritoneal dialysis (CAPD) PMID- 4028534 TI - Natural history of left anterior descending coronary artery obstruction: significance of location of stenoses in medically treated patients. AB - We examined the prognostic significance of an obstructive lesion in the proximal left anterior descending (LAD) coronary artery. Five-year or longer follow-up data were examined from 311 patients with greater than 70% obstruction of the LAD treated without surgery. Mortality was compared in subsets with lesions proximal to and distal to the first septal perforating artery. Survival curves were worse in patients with proximal than with distal LAD disease (p less than 0.05); lesion location remained a significant determinant of survival when ejection fraction, age, and sex were controlled using a Cox regression model. However, when patient subsets were examined, survival with proximal LAD disease was worse than with distal obstruction only in the presence of an associated right coronary artery lesion and an ejection fraction of less than 40% (p less than 0.01). Patients with proximal LAD plus right coronary lesions had a 5-year mortality rate (34.08 +/- 8.9%) that was not significantly (p greater than 0.05) different from that of a group of 66 patients with greater than 50% narrowing of the left main coronary artery (24.02 +/- 4.3%). Thus, proximal LAD disease is more significant than is a distal lesion only in the presence of right coronary obstruction. This two-vessel combination results in a mortality rate as high as that associated with left main coronary artery obstruction. PMID- 4028535 TI - Is the blood pressure the same in both arms? AB - It is generally believed that there are blood pressure differences between the right and left arms, but most of the validation studies have used nonsimultaneous measurements. It is important to know whether there is a difference, as methodological comparisons are often made using a different technique on each arm. We have measured the blood pressure simultaneously in both arms in 91 patients, using two observers and two cuffs to provide eight measurements in a fully balanced design. The mean difference in blood pressure between the arms (left/right) was -1.3 (SE 0.4)/1.1 (SE 0.3) mmHg. Mean differences of the same magnitude were found between the two observers, and between the cuffs. Thus, no systematic difference of any consequence was found, although individual patients had mean between-arm differences in blood pressure of up to 10 mmHg. These results suggest that no significant bias is introduced in methodological comparisons that use both arms. PMID- 4028536 TI - Hemodynamic advantage of combined administration of oral ibopamine and nitroprusside in patients with ischemic and idiopathic congestive cardiomyopathy. AB - The hemodynamic effects of combined administration of ibopamine (Ib) (150 mg orally) with nitroprusside (NP) (50-150 micrograms/min intravenously) were compared with those of NP alone in 17 patients with severe congestive heart failure due to coronary artery disease (7 patients) or idiopathic cardiomyopathy (10 patients). Hemodynamic measurements were obtained using a Swan-Ganz thermodilution catheter and a bedside thermodilution cardiac output computer. Nitroprusside alone produced a significant decrease (-12.4%) in mean arterial pressure, mean pulmonary arterial pressure (-28.3%), and systemic vascular resistance (-22.6%), and a significant increase in stroke volume index (23.1%). The administration of combined NP and Ib produced a further significant increase of stroke volume index (20.1%) with a concomitant and significant reduction of systemic vascular resistance (-19.4%); heart rate, mean systemic and pulmonary arterial pressures did not change significantly from the values observed with NP alone. Moreover, stroke work index, although not significantly modified with the vasodilator alone, was significantly increased over control values with NP + Ib association. Although NP alone induced similar effects in both the ischemic and idiopathic cardiomyopathies, the association of Ib gave a more favorable, though not significant, hemodynamic response in the subjects with primitive cardiomyopathy than in the ischemic ones. Thus, the association of Ib to NP therapy, in patients with congestive heart failure, further increases stroke volume index and stroke work index with a concomitant reduction of systemic vascular resistance, without any significant change in mean systemic and pulmonary arterial pressures, or heart rate. These results point out the possibility of associating Ib with other orally active vasodilators in the chronic treatment of congestive heart failure. PMID- 4028537 TI - Ruptured abdominal aortic aneurysms: experience with 70 cases. AB - During the period 1965-1983, 270 patients underwent resection of abdominal aortic aneurysm. In 70 patients (26%) the aneurysm was ruptured. Overall hospital mortality of patients with ruptures was 34%. Five patients died before the graft could be completed. Common denominators associated with mortality were hypotension, renal failure, cardiac arrest, and postoperative hemorrhage. The average age over the first 10 years was 68, but subsequently, has risen gradually, with a corresponding increase in mortality despite improved surgical technique and postoperative care. Only with more widespread elective resections and earlier diagnosis of rupture followed by prompt operative management, can the outlook for patients with abdominal aortic aneurysm be improved. PMID- 4028538 TI - Primary sarcoma of the pulmonary trunk: successful surgical intervention and prolonged survival. AB - We present a rare case of pulmonary trunk sarcoma in a young male in which the diagnosis was made antemortem. Total surgical removal of the tumor, including replacement of the pulmonary valve, was undertaken. This patient is the longest reported survivor of pulmonary trunk sarcoma and remains free of any signs or symptoms of recurrence. No adjuvant chemotherapy was required. PMID- 4028539 TI - Ochronotic cardiovascular disease. AB - Ochronosis is a disease of tyrosine metabolism. Although most commonly associated with alcaptonuria and spondyloarthropathy, cardiovascular abnormalities have been associated. We describe a case which exemplifies the cardiovascular findings in this entity. PMID- 4028540 TI - Myositis ossificans of the thigh following manipulation of the knee. A case report. AB - Myositis ossificans of the thigh produced severe limitation of knee motion in a 22-year-old man after passive manipulation of a knee on three separate occasions. Motion improved after excision of the bony mass and postoperative radiation to prevent recurrence. Caution is advised in passive manipulation of the knee, because repeated attempts can result in forced extension of the quadriceps muscle, periosteal damage, partial muscle tears, and interstitial hemorrhage. PMID- 4028541 TI - The effect of running on the pathogenesis of osteoarthritis of the hips and knees. AB - Former college varsity athletes were surveyed by questionnaire to determine if long-distance running can be implicated as a factor in the future development of osteoarthritis of the hips and knees. Subjects were divided into two groups. One group consisted of 504 former varsity cross-country runners. A control group consisted of 287 college swimmers. Follow-up periods ranged from two to 55 years, with a mean of 25 years. In former runners there was a 2% incidence of severe pain of the hips and knees. In former swimmers there was an incidence of 2.4%. Additionally, 2.1% of swimmers eventually had had a surgical procedure for relief of pain. Only .8% of runners eventually required surgery for osteoarthritis. There is no association between moderate long-distance running and the future development of osteoarthritis. Furthermore, the evidence suggests that neither heavy mileage nor the number of years running are contributory to the future development of osteoarthritis. PMID- 4028542 TI - Surgical and nonsurgical treatment of acute ankle sprains. AB - In the treatment of eversion injuries or tears of the medial structures, exact anatomic restoration is mandatory, and this must be accomplished by either closed reduction or surgery. The treatment of lateral ankle ligament injuries is usually cast immobilization, taping, or a cast-brace. Surgical treatment of lateral ankle ligament sprains is performed only on those highly competitive young individuals who require an almost normally functioning ankle. PMID- 4028543 TI - Ankle injuries in skiing. AB - With the development of new ski equipment and improvement in skiing techniques and slope grooming, the incidence, mechanism, and type of ankle injuries suffered during skiing have changed. Ankle sprains, peroneal tendon dislocations, Achilles tendon ruptures, and ankle fractures all can happen as the result of skiing. However, the incidence of these injuries has been dramatically lowered in the past two decades. All of these injuries should be treated aggressively to allow the skier to return to skiing. The early functional treatment of acute ankle sprains will return many skiers to activity quickly. With ankle fractures, lateral subluxation of the talus must be diagnosed and will be the determinant as to whether nonoperative or operative treatment is necessary. Open reduction with plating of the fibula and early weight-bearing in a brace allows early functional return to the ankle. PMID- 4028544 TI - Shoulder impingement syndrome in athletes treated by an anterior acromioplasty. AB - Shoulder pain caused by a impingement syndrome commonly affects an athlete's performance. Thirty-five shoulders in 33 athletes had an impingement syndrome treated by an anterior acromioplasty after failure of conservative treatment. Thirty-one of 35 shoulders (89%) were subjectively judged improved by the patients from their preoperative status. The moderate and severe pain was reduced from 97% of the shoulders preoperation to 20% postoperation. The pain at rest and with activities of daily living was reduced from 71% of the shoulders preoperation to 9% postoperation. However, only 15 of 35 operated shoulders (43%) allowed return to the same preinjury level of competitive athletics, and only four of 18 athletes involved in pitching and throwing returned to their former preinjury status. This operation is satisfactory for pain relief but does not allow an athlete to return to his former competitive status. A prolonged rehabilitation program may improve the results. PMID- 4028545 TI - Sports following spinal surgery in the young athlete. AB - The decision to allow any young athlete to resume sports participation following injury or surgery must always be individualized. In the case of spinal surgery, whether it is of the decompressive type or involves spinal fusion, the decision to return to full sports participation must take into consideration not only the level of the spine involved but also the extent of spinal fusion. The potential for segmental instability immediately above or below the fusion site as well as any neurologic injury identified at the time of the initial injury or subsequently noted in the course of management must also be taken into account. PMID- 4028546 TI - Nutrition in sports medicine. AB - Strenuous or vigorous exercise does not appear to significantly alter the requirements for any specific nutrient except calories. The major nutritional problem in sports medicine, particularly among the young, will be one of meeting caloric requirements from a variety of foods. As high- or low-energy requirements are met, so will requirements for all other essential nutrients. We should all heed the words of Sir Robert Hutchison (1871-1960), as perhaps the Food and Nutrition Board did. He wrote in the New Castle Medical Journal, vol. 12, 1932, "One swears by whole meal bread, one by sour milk; vegetarianism is the only road to the salvation of some, other insist not only in vegetables alone, but on eating those raw. At one time the only thing that matters is calories; at another time they are crazy about vitamins or about roughage. Scientific truth may be put quite briefly; eat moderately, having an ordinary mixed diet and don't worry." Robert Charles Benchley (1889-1945), an American humorist, critic, and actor, was known to say that when the thought of exercise came upon him, he would lie down until the thought passed over. Clement Richard Attlee (1883-1967), prime minister of the United Kingdom from 1945 to 1951, said he owed his long life to resisting all forms of exercise. PMID- 4028547 TI - The use and abuse of anabolic steroids in Olympic-caliber athletes. AB - Self-medication with anabolic steroids by athletes, particularly in the sports of weight lifting and track and field, has become increasingly popular. In the 1983 Pan American Games, 15 athletes were disqualified for taking anabolic steroids. Athletes take steroids believing the steroids will allow increased periods of intensive training and will increase muscle strength with proper weight training. The athletes assume this increased strength and training will translate into better athletic performance. Most athletes taking anabolic steroids are taking very large doses with no thought as to the potential adverse side effects. They ignore the possibility of long-term problems relating to hypertension, liver dysfunction, and atherosclerosis for what they see as the immediate performance benefits. In an attempt to keep sports competition "clean" and to help protect athletes from harmful drugs, the International Olympic Committee (IOC) and the United States Olympic Committee have rules stating that the use of anabolic steroids is illegal. Drug testing is performed in Olympic and in many international competitions. Those people found using anabolic steroids are disqualified. This use of anabolic steroids indicates that for some athletes the need to win or to maximize performance supersedes any worries about future health. PMID- 4028548 TI - The diagnostic accuracy of spinal nerve injection studies. Their role in the evaluation of recurrent sciatica. AB - The spinal nerve injection study (SNIS) is a diagnostic test for the evaluation of sciatica. SNIS consists of selective infiltration of nerve root with local Xylocaine anesthesia. The most common indication is in the postlaminectomy patient with persistent or recurrent sciatica and peridural scarring causing myelograms or CT scans to be difficult to interpret. Of 105 patients with SNIS, 55 subsequently had surgical exploration of the suspected lesion. In patients with a diagnostic or highly suggestive SNIS, an accurate diagnosis was made in 43 (93%); myelograms in the same group had an accuracy of 24%. At follow-up evaluations ranging from 12 to 60 months (average, 20 months), 40 (73%) of the patients were improved by further surgical treatment. PMID- 4028549 TI - Partial epiphysiodesis at the knee to correct angular deformity. AB - A method of partial epiphysiodesis is described for correction of idiopathic genu valgum or varum in the adolescent patient. A standard curve is used to determine the proper timing for partial epiphysiodesis, including allowance for the remaining growth to correct the deformity before skeletal maturity is reached. The surgical technique is designed to produce partial epiphysiodesis of the femur and/or tibia. The advantages of this procedure are predictability, a small scar, and the avoidance of a second procedure. The results in 13 extremities treated and followed to maturity demonstrate the efficacy of the operation. PMID- 4028550 TI - An investigation of the digital nerves of the thumb. AB - With the use of a stereoscopic microscope, observations were made on the course of the proper digital nerve of the thumb on ten upper limbs in adult cadavers. By observation from the dorsal side after removal of the bone, it was possible to clearly see the ramification of the digital nerve from the subcutaneous tissue to the dermis. Ramification from the palm to the level of the interphalangeal joint was segmental. The digital nerve of the thumb trifurcates from the proximal site of the distal palmar thumb crease into the main, medial, and lateral branches. The main branch is thick and extends from the center of the pulp toward the fingertip. Ramification at the pulp of the thumb is of a radiating rather than segmental type, and its control can be considered as spotty or intermittent. Distribution of pacinian corpuscles is dense in the subcutaneous tissue of the distal palmar thumb crease. These observations are of clinical importance not only for avoidance of injury to the digital nerve in surgical procedures such as the incision and drainage for felon and the trigger thumb release but also for precise repair of the digital nerve in the reconstructive surgery of the thumb. PMID- 4028551 TI - Results of carpal tunnel release in renal hemodialysis patients. AB - Forty-eight renal hemodialysis patients were evaluated clinically and electrodiagnostically for carpal tunnel syndrome (CTS). The incidence (32%) was significantly higher than that previously reported by other authors. All patients with CTS also had peripheral neuropathy by electrodiagnostic criteria. CTS was found four times as often in patients who had dialyzed longer than five years compared to those who had dialyzed less than five years. Patients with CTS were more likely to have an active or inactive access in the involved forearm than were patients without CTS. In patients with CTS treated by transverse carpal ligament release, 87.5% obtained relief from pain and numbness. Because of the high incidence of CTS in the chronic hemodialysis population, electrodiagnostic screening is recommended in these patients. Patients with clinical and electrodiagnostic signs of CTS will benefit from transverse carpal ligament release. PMID- 4028552 TI - Correction of chronic lateral ligament instability of the ankle by use of the Brostrom procedure. A report of 15 cases. AB - This paper presents experience with the Brostrom operation, a relatively unknown surgical procedure for treating chronic instability, pain, and swelling involving the lateral aspect of the ankle. The procedure is indicated in patients unresponsive to conservative therapy. The torn ligament ends are identified and either reapproximated or reattached to the lateral malleolus or talus, depending on the site of original rupture. Of 15 consecutive patients treated, 13 obtained good or excellent results. Adequate ligamentous tissue for reconstruction was present in all cases. Stability, the primary goal in reconstructing these ligaments, was improved in all cases. Other surgical procedures for treating this symptom complex use normal anatomic structures (usually the peroneus brevis tendon) for reconstructing the anterior talofibular and/or calcaneofibular ligaments. The Brostrom procedure offers results comparable to other techniques but is superior because it is unnecessary to alter any normal anatomic structures. PMID- 4028553 TI - A method of evaluating the results of forefoot surgery. AB - Clinical evaluation of the foot is complicated because of the large number of structures, most of which are difficult to record or measure. A standardized system of evaluation is needed to assess the ever-increasing methods of treating foot abnormalities. An evaluation form for recording clinical information on forefoot operations has been designed and can be specifically used for computerized data retrieval. In designing the form, an attempt has been made to standardize methods of clinical examination (mainly on the forefoot) and enable accurate comparisons of data from similar studies in the literature. Two hundred thirty-two specific items are included in the form. More data are available on the forefoot because this part of the foot can be more readily evaluated clinically. Also, it is usually the area of the more extreme pathologic changes and largest number of procedures. Specific entries cover details of the history, physical signs, diagnosis, pain assessment, shoes, walking, function, general and surgical treatment, and complications. The form is applicable to computer methods or data retrieval. PMID- 4028554 TI - Extraskeletal soft-tissue chondrosarcoma. Case report and review of the literature. AB - A rare extraskeletal soft-tissue chondrosarcoma of the foot occurred in a 50-year old man. Adequate en-bloc excision or amputation was the indicated method of treatment. PMID- 4028555 TI - Methicillin-resistant Staphylococcus aureus osteomyelitis. AB - In five patients, the diagnosis of methicillin-resistant Staphylococcus aureus (MRSA) osteomyelitis was made by clinical and roentgenographic methods and confirmed by bone biopsy cultures. The treatment was staged according to the anatomic setting of the infection and the systemic and local competence of the host. Seven episodes of osteomyelitis were encountered in the five patients. Two patients had persistence of their infection and were successfully treated by additional surgical debridement, antibiotics, and adjunctive hyperbaric oxygen. Vancomycin was administered to all patients. The daily dosage of vancomycin ranged between 100 mg and 2.0 gm. The length of vancomycin therapy ranged from 19 to 56 days. Five of seven biopsy specimens grew bacterial organisms in addition to MRSA. The MIC of vancomycin for MRSA ranged between 0.39 and 1.56 micrograms/ml. Osteomyelitis was arrested in five of seven episodes, and follow up evaluations ranged from two to 35 months. Two of five (40%) patients receiving the combination of vancomycin and tobramycin developed signs of renal toxicity. Renal function returned to normal after discontinuation of the antibiotics. MRSA osteomyelitis is usually acquired by spread from a contiguous focus of infection and is often polymicrobic in nature. Treatment with vancomycin or vancomycin plus tobramycin when the infection was polymicrobic was effective. The combination of vancomycin plus tobramycin is potentially nephrotoxic. PMID- 4028556 TI - Muscle biopsy: proper surgical technique. AB - Muscle biopsy is often incorrectly performed despite the fact that it is a relatively simple procedure. A consistently reproducible surgical technique in 93 open vastus lateralis muscle biopsies implemented in conjunction with neuromuscular and malignant hyperthermia research demonstrated 14 cases of malignant hyperthermia and a variety of forms of neuromuscular pathology. No wound complications or disabilities have resulted from this procedure. The procedure includes careful selection of biopsy site, regional anesthesia, atraumatic dissection, and immediate processing of the biopsy sample. A new muscle biopsy clamp is described. The authors recommend the vastus lateralis for the biopsy site unless another area of involvement is specifically indicated. Careful attention to technical details is required for optimal results. PMID- 4028557 TI - Shoulder arthrodesis for the treatment of brachial plexus palsy. AB - In 14 adult patients with brachial plexus injuries, shoulder arthrodesis was completed in a position of 30 degrees abduction, 30 degrees flexion, and 30 degrees internal rotation. Abduction was measured by the position of the arm in relation to the side of the body with the scapula in the anatomic position. Internal fixation was used in each case. Six patients had had Steindler procedures. Three patients with complete paralysis were treated by above-elbow amputation. All shoulders fused. Mean follow-up time was 32 months. All patients noted that shoulder fusion had improved the function of their extremities. Minimum shoulder motion was 60 degrees abduction and 50 degrees flexion. Three procedures failed because of continued pain that was not relieved by surgery. One patient with an elbow flexion contracture disliked the combination of shoulder and elbow flexion. Seven patients required plate removal. Only one of the three patients who had had above-elbow amputation became a good prosthetic user. Shoulder arthrodesis is a reliable procedure that improves function in adult patients with brachial plexus palsy. PMID- 4028558 TI - Computerized tomographic determination of vertebral density after total hip arthroplasty. AB - Computerized tomography (CT) provides the capability to determine vertebral bone density with a high degree of accuracy and precision, detecting density changes as small as 5% in serial testing. In this pilot study, CT was used to determine the effects of total hip arthroplasty and its consequent alterations in physical activity levels on the vertebral bone density of 13 postoperative patients. Vertebral bone density was also evaluated in six preoperative patients with degenerative joint disease of the hip and five control patients. The preoperative group and controls were then compared with the postoperative patients, who were divided into two groups--those who had achieved good activity levels and those whose levels of activity remained poor. CT measurement of bone density in the central bodies of T12, L1, and L2 showed that the preoperative group was similar to controls. This suggests that patients accept total hip arthroplasty rather than endure significant activity limitations for extended periods of time. When activity level was restored by arthroplasty, vertebral bone density was preserved. If the patient continued at a poor activity level postoperation, significant loss of bone density occurred secondary to disuse. PMID- 4028559 TI - Squamous cell carcinoma in chronic osteomyelitis. Report of a case and review of the literature. AB - Malignant change at the site of a chronic osteomyelitis, a rare condition, is reported in a 45-year-old man, along with a review of the literature. This patient with a 30-year history of chronic osteomyelitis of the right femur and an intermittently discharging sinus had a large abscess in the lower thigh. The abscess was drained, and an ulcer developed at the mouth of the sinus tract. Soon afterward, he sustained a pathologic fracture through the lower femur. Biopsy specimens of the ulcer showed a well-differentiated squamous carcinoma. An amputation was performed at the level of the proximal 10 cm of the femur. The patient remains well 18 months later with no clinical or radiologic evidence of metastases. Changes in character of a previously innocuous osteomyelitis sinus tract should arouse suspicion of neoplastic transformation. Biopsy of various depths of the sinus tract, including the bone marrow, is essential. Early amputation for squamous cell carcinoma is indicated and offers a good prognosis. PMID- 4028560 TI - The effect of alignment on results in arthroscopic debridement of the degenerative knee. AB - Fifty-two patients with severe degenerative joint disease of the knees were treated by arthroscopic debridement. The results of arthroscopic debridement on normally aligned degenerative knees are encouraging. A combination of arthroscopic debridement and high tibial osteotomy could be an appealing alternative to total knee arthroplasty in the young patients. Patients with varus angular deformity in the degenerative knee had a poor result and should be excluded from consideration for arthroscopic debridement. PMID- 4028561 TI - Posterior spinal fusion without blood replacement in Jehovah's Witnesses. AB - Posterior spinal fusion without blood replacement is a formidable procedure that most orthopedic surgeons are reluctant to attempt. This procedure has been performed without transfusions on 19 patients, all of whom were Jehovah's Witnesses. The operations were performed over four spinal segments at a time and were planned so that the procedure could be terminated when 10% of the patient's estimated total blood volume had been lost. Allogeneic donor bone was used to minimize blood loss whenever this was acceptable to the patient. The procedure was associated with a high incidence of pseudarthrosis, all cases of which occurred when allogeneic bone was used. No deaths or life-threatening complications were encountered. Thus, posterior spinal fusion can be performed in Jehovah's Witnesses without transfusion, but the procedure should be conducted only by the experienced spinal surgeon. PMID- 4028563 TI - Nuclear magnetic resonance studies of fracture repair. AB - High-resolution phosphorus nuclear magnetic resonance spectroscopy was used to monitor noninvasively the local pH changes that occur in vivo throughout fracture repair in rats. During the healing of a fractured shaft of tibia, the pH of the fracture hematoma changed from 7.2 on day two to 7.5 on day 20, i.e., alkaline with respect to the pH of normal extracellular fluid. This did not occur in a hematoma created by the direct injection of blood. Deposition of radio-opaque callus occurred mainly during the alkaline phase. Abnormalities in the control of local pH may be important in the etiology of delayed union, and future forms of local therapy may be usefully directed toward influencing this parameter. PMID- 4028562 TI - Effect of partially purified bone morphogenetic protein on DNA synthesis and cell replication in calvarial and fibroblast cultures. AB - The effects of bone morphogenetic protein (BMP), a molecule extracted from demineralized bone, were observed in organ cultures of 21-day fetal rat calvariae. The effects of BMP on cell replication in cultures of normal rat kidney (NRK) fibroblasts were studied for comparison. At concentrations of 0.1-10 micrograms/ml for periods of 24-96 hours, BMP stimulated the incorporation of 3H thymidine into acid-insoluble residues (DNA) in calvariae by 25%-159%, and at 1 10 micrograms/ml it increased bone DNA content by 20%-23%. BMP at 1 micrograms/ml also increased the number of calvarial mitoses after colcemid arrest by 1.5-1.8 fold. The effect of BMP on calvarial DNA synthesis was observed in the periosteal bone. In contrast to its effects on DNA synthesis, BMP did not stimulate the incorporation of 3H-proline into collagenase-digestible and noncollagen protein and did not alter calvarial alkaline phosphatase activity. BMP at 1-10 micrograms/ml caused a marked increase in 3H-thymidine incorporation into DNA in cultured NRK fibroblasts and increased DNA content and cell number by 1.5-2-fold. These studies indicate that BMP stimulates DNA synthesis and cell replication in calvarial and fibroblast cultures but does not stimulate postdifferentiated bone cells in incubated calvariae. PMID- 4028564 TI - Strength of stainless steel surgical wire in various fixation modes. AB - Although wire is a commonly used fixation device in orthopedics, little is known about the effects of fastening methods and configurations on the strength of wiring systems. Three sizes of stainless steel surgical wire were tested in noncyclic tensile loading. Load failure levels increased with enlarging wire diameter. Fastening twists were stronger than knots or the ASIF bend technique. The failure mode for twists was untwisting. More than two twists gave no additional strength to the system. Two commercial wire tightening devices gave stronger and more reproducible twists than did ordinary pliers. The addition of a tension equalizing loop opposite the fastening loop weakened the wire system by 10%-15%. The combination of two single wire loops was stronger than a continuous double loop of wire. The results from this study are intended to help the orthopedic surgeon optimize the use of wire. PMID- 4028565 TI - Supracondylar humeral osteotomy for traumatic childhood cubitus varus deformity. PMID- 4028566 TI - Rating systems in the evaluation of knee ligament injuries. AB - Many different methods of evaluating disability after knee ligament injury exist. Most of them differ in design. Some are based on only patients' symptoms. Other include patients' symptoms, activity grading, performance in a test, and clinical findings. The rating in these evaluating systems can be either numerical, as in a score, or binary, with yes/no answers. Comparison between a symptom-related score and a score of more complex design showed that the symptom-related score gave a more differentiated picture of the disability. It was also shown that the binary rating system gave less detailed information than a score and that differences in a binary rating can depend on at what level the symptoms are regarded as "significant." A new activity grading scale, where work and sport activities were graded numerically, was constructed as complement to the functional score. When evaluating knee ligament injuries, stability testing, functional knee score, performance test, and activity grading are all important. However, the relative importance varies during the course of treatment, and therefore they should not all be included in one and the same score. PMID- 4028567 TI - Double-contrast CT arthrography of the cartilage of the patellofemoral joint. AB - For assessment of the value of computed tomography (CT) as a method for evaluating the cartilage of the patellofemoral joint, 100 knees were examined in 91 patients. With the patient in a supine position with the knee flexed at a 30 degree angle, a sufficient quantity of air and positive contrast material was required to obtain an accurate CT picture of the cartilage. Normal cartilage images of 53 knees and abnormal images of 47 knees were obtained by use of CT. The latter group was classified into eight types. When the CT findings of 70 knees were compared with arthroscopy and/or arthrotomy, the results showed that CT diagnosis was accurate in 68 of 70 knees, with a coincidence rate of 97.1%. Cartilage thickness at an arbitrary site and the extent of the ulcer within the deep layers were observed easily by CT. Although examination exclusively with arthroscopy had distinct disadvantages (e.g., the inability to assess either the specific thickness of the cartilage or the extent of the ulcers within deep layers), the combined use of arthroscopy with CT provided a precise three dimensional image of the cartilage. CT was found to be a valuable noninvasive imaging method for patellofemoral joint cartilage evaluation. PMID- 4028568 TI - A perspective of lesions associated with ACL insufficiency of the knee. A review of 100 cases. AB - A retrospective study was conducted to survey the extent of intracapsular damage associated with ACL insufficient knees in both the acute and chronic situation. Previously unoperated knees were studied to assess the effect that reinjury had on the knee joint. One hundred patients with confirmed anterior cruciate ligament damage, both clinically and under general anesthesia, were examined arthroscopically and the findings recorded on video tape. Both anterolateral and posteromedial approaches were used to well visualize the entire intra-articular structures of the knee joint. The incidence of meniscal tears increased from 77% in the acute injury to 91% in the chronically reinjured knee (p less than .06). Furthermore, articular surface disease increased from 23% in the acute injury to 54% in the chronically ACL lax knee (p less than .002). The majority of meniscal tears were medial and amenable to peripheral suture repair (63%). Irrespective of how one approaches ACL insufficiency of the knee acutely, one cannot ignore the likelihood of finding these significant associated lesions. Reinjury to the knee will likely enhance the incidence of meniscal tears and articular changes. PMID- 4028569 TI - Secondary reconstruction of the anterior cruciate ligament (ACL) in competitive athletes. AB - A follow-up study of 325 patients with surgical repair of ligamentous lesions from 1971 to 1977 demonstrated 88% good results in a group treated by one operation. Only 66% of patients who had had two or more operations had good results. High-performance athletes may regain a reasonably good level of function if knee joint instability is limited to anterior cruciate ligament instability. Superimposed injury causing rotatory instability significantly reduces the incidence of good recovery of function even if repaired by the best known surgical procedures. Function sufficient for noncontact, nonviolent sports is often possible. A poor prognosis for long-term joint function is attributable to chondromalacia and accompanying proliferative synovitis. The earlier a ligamentous lesion is repaired, the better the prognosis. PMID- 4028570 TI - Complete knee dislocation. A follow-up study of operative treatment. AB - Twenty knee dislocations in 19 patients (one bilateral) occurred over a period of 20 years. The age range was 21 to 65 years, with an average age of 40.8 years. There were two popliteal artery and eight peroneal nerve injuries in the group. All patients were managed by early closed reduction at the scene of the accident or at the admitting hospital. Treatment consisted of 13 acute arthrotomies with complete ligamentous repair, one partial ligament repair, two delayed repairs, and four cast applications. Both anterior and posterior cruciate ligaments were torn in each knee surgically examined. In contrast to cruciate injuries in nondislocated knees, avulsion of bone of the PCL was present in 14 of 16 and of the ACL in ten of 16. Complete follow-up study including examination and radiographic evaluation was obtained on 18 knees in 17 patients. Special investigations of 13 with acute complete ligament repair, followed from 12 months to 48 months (average of 24 months), showed loss of joint motion following this injury. Clinical instability was generally not a problem, but chronic pain and discomfort were present in 46%. The average knee diagnostic score was 43. Seventy seven percent of the patients returned to vigorous sports activities. Early operative repair followed by cast bracing and manipulation at three months (if flexion was less than 90 degrees) is recommended in young, active patients. PMID- 4028571 TI - [Peripheral nerve involvement in spino-cerebellar degenerations. 3. Atypical cases]. PMID- 4028572 TI - [Gait apraxia with cluttering-like speech disturbance]. PMID- 4028573 TI - [Spinocerebellar degeneration associated with bilateral basal ganglia calcification, macular degeneration and mental retardation--case report of two siblings]. PMID- 4028574 TI - [Myotonic discharges in a case of licorice-induced hypokalemic myopathy]. PMID- 4028575 TI - [An autopsy case with lymphomatoid granulomatosis (Liebow) involving the brain]. PMID- 4028576 TI - [A case of chronic progressive radiation myelopathy with a CT myelogram simulating an intramedullary tumor]. PMID- 4028577 TI - [Computed tomography in Duchenne type muscular dystrophy--morphological stages based on the computed tomographical findings]. PMID- 4028578 TI - [Differential diagnosis of parkinsonism based on a semiquantitative scoring system--chiefly to discriminate two major causes, paralysis agitans and vascular parkinsonism]. PMID- 4028579 TI - [Acute orbital myositis--a case of inflammatory orbital pseudotumor characterized by enlargement of localized extraocular muscles]. PMID- 4028580 TI - [Progressive subcortical vascular encephalopathy, alopecia, and spondylosis- report of a case and proposal of a new progeroid syndrome]. PMID- 4028581 TI - [Two cases of cervical intradural arachnoid cysts simulating juvenile muscular atrophy of a unilateral upper extremity (Hirayama's disease)]. PMID- 4028582 TI - [Abnormal radiological findings in juvenile-type distal and segmental muscular atrophy of the upper extremities]. PMID- 4028583 TI - [Biochemical studies on experimental chloroquine myopathy]. PMID- 4028584 TI - Intracranial bilateral symmetrical calcification on CT-scanning. A case report and a review of the literature. AB - The case of a 57-year-old woman with idiopathic hypoparathyroidism is presented. A CT-scan showed extensive bilateral symmetrical calcification in the region of the basal ganglia, nuclei of the cerebellum and the cerebral and cerebellar white matter. A review of the literature showed that bilateral symmetrical calcification detected by CT is usually small in extent and is most often confined to the globus pallidus. It is most commonly found in patients older than 50 years, who only rarely have symptoms associated with it. The finding is, though, non-specific and may occur in a variety of pathological conditions both with and without an aetiological relationship. Further study of the cerebral parathormone responsive adenylate cyclase enzyme proves hopeful to elucidate the aetiology of idiopathic bilateral symmetrical calcification. PMID- 4028585 TI - Bruxism: its significance in coma. AB - Bruxism, the phenomenon of non-functional grinding of the teeth has been ascribed to various causes. Twenty patients with coma from different causes who displayed bruxism were studied with an attempt to correlate the phenomenon to the level of consciousness, eye movements, respiration, cold caloric test, motor deficits and sleep wake cycles. Bruxism was seen to appear at different levels of consciousness, but to disappear only after a significant improvement in the level of consciousness. A relationship with the appearance of sleep wake cycles was also seen. PMID- 4028586 TI - A cerebral cause of arthrogryposis: unilateral cerebral hypoplasia. AB - The authors describe a case of predominantly right-sided arthrogryposis in an infant with contralateral congenital cerebral hypoplasia and associated unilateral hydrocephalus. Diagnosis was made by prenatal ultrasonography and confirmed by postnatal cerebral CT-scanning. In addition to a variety of congenital neuromuscular disorders, arthrogryposis may be caused by disorders of the central nervous system. Hence, in the diagnostic approach of newborns with congenital contractures, cerebral malformations must be considered. PMID- 4028587 TI - Mollaret's meningitis responding to phenylbutazonum. A case report. AB - A patient with Mollaret's meningitis is presented, with some unusual features. Criteria for the diagnosis are discussed. Many therapies for this recurrent aseptic meningitis have been suggested. In our patient there was a good response to phenylbutazonum, which to our knowledge has not been reported before. PMID- 4028588 TI - Anaerobic meningitis in an infant associated with pilonidal cyst abscess. AB - A 5-month-old infant whose infected pilonidal sinus was surgically removed, developed meningitis due to Bacteroides fragilis. A similar organism was also recovered from the infected pilonidal cyst along with anaerobic Gram positive cocci. The patient was treated with intravenous chloramphenicol for 4 weeks and recovered without sequela. Attention should be paid to the possibility of meningitis due to anaerobes in children with an infected pilonidal sinus. PMID- 4028589 TI - Remission of a paraneoplastic cerebellar syndrome. AB - A case history is reported of spontaneous improvement of a sub-acute paraneoplastic cerebellar syndrome, that is before treatment of the primary (lung) tumour. PMID- 4028590 TI - Solitary osteochondroma of spine causing spinal cord compression. AB - Three cases of spinal cord compression due to solitary osteochondroma of the spine are reported. The rarity and benign nature of the tumour is stressed. Other reported cases are reviewed. PMID- 4028591 TI - Neuropathy of the ulnar nerve caused by an aneurysm of the ulnar artery at the wrist. A case report and review of the literature. PMID- 4028592 TI - Livedo racemosa generalisata and stroke. AB - The authors describe three young female patients with generalized livedo racemosa and cerebral infarction. The radiologic and biopsy findings point to a widespread vasculopathy, involving small and mid-sized arteries. The histologic examination of the temporal artery biopsy in two patients gives additional evidence for a chronic endarteritis as possible underlying cause of this disease entity. PMID- 4028593 TI - Percutaneous radiofrequency Gasserian ganglion coagulation in the treatment of trigeminal neuralgia. AB - Fifty-three patients with trigeminal neuralgia were treated with percutaneous radiofrequency Gasserian ganglion coagulation. An individually adjusted degree of coagulation was applied. The procedure was successful in 45 patients (85%). The median follow-up was two years; only two of the remaining 45 patients had relapse of symptoms. Four patients experienced side effects consisting of troublesome facial dysaesthesia. Our data indicate that percutaneous radiofrequency coagulation of the Gasserian ganglion is a safe and reliable procedure in the treatment of medication resistant trigeminal neuralgia. PMID- 4028594 TI - Heart rate variability of chronic alcoholics in withdrawal and abstinence. AB - Measurement of heart rate variability was performed in 106 healthy volunteers and 31 alcoholics. The mean momentary arrhythmia (MMA) of normal individuals showed an exponential decrease with increasing age. Cardiac autonomic neuropathy was found in 5 of 31 alcoholics. In agreement with the concept of hyperexcitability the withdrawing alcoholics had a significant increase in heart rate and decrease in MMA compared to later measurements. The result suggests that the diagnosis of autonomic alcoholic neuropathy may be reliable only after at least a one week period of abstinence from alcohol. PMID- 4028595 TI - On the lethality of acute respiratory component of tardive dyskinesia. AB - Acute respiratory component of tardive dyskinesia, though reported very infrequently, is a potentially lethal condition necessitating urgent intervention. Several relevant issues are discussed with an illustrative case material. The need to differentiate respiratory dyskinesia from psychogenic hyperventilation is emphasized. Use of neuroleptics is discouraged to avoid unfavourable long-term outcome. PMID- 4028596 TI - Comparison of technetium-99m pyrophosphate and technetium-99m methylene diphosphonate with variable amounts of stannous chloride in the detection of acute myocardial infarction. AB - The authors prospectively compared the ability of Tc-99m pyrophosphate (PYP) and Tc-99m methylene diphosphonate (MDP) to detect acute myocardial infarctions. The agents used were PYP (12 mg) with 3.4 mg of stannous chloride, MDP (10 mg) with 1.0 mg of stannous chloride, and MDP (10 mg) with 3.4 mg of stannous chloride. Imaging was performed on three consecutive days on 34 patients with proven myocardial infarctions, using the same agent on the first and third days of the study and an alternate agent on the second day. Agents were assigned randomly to each of six groups of patients. First images were obtained an average of 3.7 days (range, one to six days) following myocardial infarction. Seventeen of 23 patients (75%) had images positive for acute myocardial infarction with Tc-99m PYP, whereas only two of 21 patients (9.5%) had positive studies with Tc-99m MDP with 3.4 mg of stannous chloride and one of 24 patients (4.2%) had positive studies with Tc-99m MDP and 1.0 mg of stannous chloride. All three myocardial infarctions detected by Tc-99m MDP were extensive and transmural. When MDP and PYP were both positive in the same patient, the apparent size of the myocardial infarction was much smaller with the MDP. It is concluded that MDP can detect only large myocardial infarctions, has poor localization in the infarcted tissue, and varying the stannous chloride content of the preparation does not improve the ability of MDP to detect acute myocardial infarctions. PMID- 4028597 TI - Scintigraphic findings in primary amyloidosis of the heart and stomach. AB - The effectiveness of scintigraphic studies in the study of patients with primary systemic amyloidosis has not been reported previously. This case report describes a patient with the scintigraphic findings of thickened myocardium and delayed gastric emptying, which correlated well with the presence of amyloid deposits in these organs at autopsy. Additionally, the liver and spleen had normal scintigraphic appearances and were free of amyloid at autopsy. Radionuclide studies appear useful in assessing the anatomic and physiologic abnormalities assessed by amyloid deposition. PMID- 4028598 TI - Failure of quality control to detect errors in the preparation of technetium-99m disofenin (DISIDA). AB - Uptake of Tc-99m disofenin is so strongly hepatobiliary that striking appearance of radioactivity in the reticuloendothelial system (RES) is almost certainly caused by improper preparation of the disofenin kit. Four patients who received injections of Tc-99m disofenin demonstrated a pronounced RES biodistribution in addition to the expected hepatobiliary pattern. Since routine quality control testing had not forewarned us of this gross lack of radiochemical purity, Tc-99m disofenin kits were subjected to a variety of insults to elucidate the mechanisms of quality control failure. Assessment of radiochemical purity was conducted using instant thin-layer chromatography (ITLC) and two solvent systems. We concluded that both Tc-99m pertechnetate and Tc-99m sulfur colloid had been injected into the cold disofenin kit. Visual inspections were not reliable for verifying the final radiopharmaceutical product because of dilution of the sulfur colloid by pertechnetate. ITLC testing failed because the assay method being used at that time did not accurately assess the hydrolyzed fraction (colloidal component). Recommendations are made to preclude recurrence of the errors that occurred. PMID- 4028599 TI - A simple data display for qualitative assessment of esophageal transit. AB - A simple data processing technique for qualitative assessment of esophageal transit is presented and its clinical value is demonstrated. PMID- 4028600 TI - A false-negative LeVeen shunt study. AB - Previous reports have indicated an accuracy of nearly 100% for LeVeen shunt studies. A case is presented that fulfills the criteria for proper function, but the LeVeen shunt tube was poorly functioning with its tip partially extravascular. PMID- 4028601 TI - Indium-111 chloride bone marrow imaging in chronic renal disease. AB - Eight patients with anemia and chronic renal disease being maintained by chronic hemodialysis were evaluated with In-111 chloride bone marrow imaging and bone marrow core biopsies. There was no correlation between the erythrocyte cellularity of the marrow and the indium bone marrow scan grade in any patient. Bone marrow imaging can not be used as an indicator of the presence of erythroid marrow in these patients. PMID- 4028602 TI - Perforated duodenal ulcer demonstrated by biliary imaging. PMID- 4028603 TI - The "gourd spleen". A positional effect. PMID- 4028604 TI - Nonvisualization of spleen following blunt trauma. PMID- 4028605 TI - Pedunculated focal nodular hyperplasia. PMID- 4028606 TI - Esophageal and other condensed dynamic images. PMID- 4028607 TI - Pathophysiology of lower urinary tract dysfunction. PMID- 4028608 TI - Genitourinary fistulas: vaginal approach for repair of vesicovaginal fistulas. PMID- 4028609 TI - Use of the artificial sphincter in the treatment of urinary incontinence. AB - Data analysis of my experience with the implantation of the artificial sphincter shows an overall success rate of 84%. These results are in 139 females ranging from 5 to 84 years of age. The surgery is difficult primarily because the urethral-vaginal septum is not a surgical plane. Even partial injury to these tissues can lead to failure with erosion of the device into the urethra or vagina. The use of a new surgical instrument, the 'cutter clamp' (Figure 8A-F), is expected to improve results because of the precision it offers in dissecting around the bladder neck. Infection occurred in four out of 139, or 3% of the cases. In one infected case, the cuff eroded into the urethra. The infection rate may actually be higher since infection might account for some of the other erosions which occurred. Once erosion occurs, secondary infection can obscure the fact that the device was contaminated at the time of the original implantation. The use of a surgical isolation bubble system may lower both the incidence of infection and erosions in the future. The relief to the totally incontinent female by the artificial sphincter cannot be overestimated. The patients are very grateful, especially since most have undergone multiple treatment methods in an effort to cure their incontinence. The effectiveness of the device, barring infection or erosion, is evident by a success of 91% of such patients being socially continent and 66% being completely dry. PMID- 4028610 TI - The unstable bladder. AB - The unstable bladder is a common clinical problem of uncertain aetiology. Current in vitro studies of unstable human detrusor samples show differences in behaviour and response to pharmacological agents from normal detrusor. The fundamental urodynamic abnormality is the occurrence of involuntary detrusor contractions which cause the cardinal symptom of urgency. The incidence of other symptoms is determined by the functional bladder capacity and the patient's ability to resist the unstable contractions. Having excluded outflow obstruction as a causative or associated factor, empirical treatment may reasonably be started on the basis of the findings of a 48-hour voided volume chart, reserving full urodynamic investigation for patients who fail to respond to treatment as expected. For those with minimal urodynamic dysfunction, bladder drill is the treatment of choice; when this fails or is inappropriate, drug treatment with oxybutynin is indicated, supplemented by other drugs when appropriate. When these standard conservative measures fail, transvesical injection of the pelvic plexuses with phenol gives worthwhile results and is a trivial procedure. If this fails, and in men in whom the phenol procedure is contraindicated, 'clam' ileocystoplasty is usually if not always curative. PMID- 4028611 TI - Vaginal prolapse affecting bladder function. AB - When pelvic reconstructive surgery is being considered, it is important that the presence of cystocele be carefully and accurately assessed preoperatively and intraoperatively so that appropriate correction can be achieved. Continence is under the influence of urethral tone and the response of the proximal urethra to changes in intra-abdominal pressure. Cranial elevation of a rotated vesicourethral junction to a normal retropubic position should be provided. Any surgical technique that alters the normal axis of the vagina should be accompanied by simultaneous obliteration of the cul-de-sac of Douglas to lessen the chance of postoperative enterocele and subsequent eversion of the vault of the vagina. When massive vaginal eversion causes displacement of the vesicourethral junction, a restoration of vaginal depth and axis by post hysterectomy transvaginal sacrospinous colpopexy with appropriate colporrhaphy will relocate a defective urethrovesical site to a higher and retropubic level within the pelvis, where the proximal urethra may once again be responsive to changes in intra-abdominal pressure. PMID- 4028612 TI - Transvaginal needle bladder neck suspension. PMID- 4028613 TI - Attention deficit disorder children with or without hyperactivity. Which behaviors are helped by stimulants? AB - Each patient with Attention Deficit Disorder (ADD), with or without hyperactivity, is unique in the variety and severity of the handicapping conditions associated with ADD. The use of a well-designed teacher rating scale can provide the clinician with a behavioral profile of each patient. The importance of knowing the child's specific problems is emphasized by the results of this research, which show that methylphenidate has a major effect in improving attention, is helpful in decreasing activity level, but often has only a minor effect on deficient social skills and oppositional (aggressive) behavior. PMID- 4028615 TI - Age-specific patterns of diagnosis of acute otitis media. AB - A retrospective review of clinical experience with the diagnosis of acute otitis media (AOM) in a large pediatric population (age, 0-12 years old) reveals two age specific patterns of diagnosis: one in preschool children and one in schoolage children. In the population as a whole, AOM is diagnosed most frequently in the first 5 years of life; rates of diagnosis vary with gender (male: female ratio = 1.10) and season (fall/winter peak). In a linear regression model, age, gender, season, and interactions among these account for 52 percent of the variability in diagnostic rates. In children less than 5 years of age, rates of diagnosis vary strikingly with gender and season; the regression model accounts for 55 percent of observed variability in diagnostic rates. In schoolage children (5-11 years old), however, males and females are equally likely to be diagnosed to have AOM, and seasonal variability is blunted; among these children, the regression model predicts only 22 percent of diagnostic rate variability. These findings buttress existing knowledge of the epidemiology of AOM and have important implications for clinical practice, health planning, and pediatric research. PMID- 4028614 TI - Adverse effects of meperidine, promethazine, and chlorpromazine for sedation in pediatric patients. AB - A combination of meperidine (M) 25 mg/ml, promethazine (P) 6.5 mg/ml, and chlorpromazine (C) 6.5 mg/ml is widely used to produce sedation in pediatric patients. A dose of MPC 0.1 ml/kg is recommended for cardiac catheterization, but no specific guidelines for dosing or frequency of monitoring have been established for patients undergoing other types of procedures. The adverse effects of MPC were studied prospectively in 95 patients undergoing various procedures. MPC was given parenterally at a dose of 0.07-0.11 ml/kg. Four patients developed respiratory depression. In these patients, the lowest respiratory rate ranged from 12 to 20 per minute. The lowest pulse rate ranged from 92 to 102 per minute. Three patients had received recommended or lower than recommended doses of MPC. One who received MPC 0.07 ml/kg developed respiratory arrest within 30 minutes; another required naloxone, and all recovered within 10 hours. These cases suggest the need for frequent monitoring and specific dosing guidelines for MPC use in pediatric patients. PMID- 4028616 TI - Leg-length inequality in hemophilia. An interesting case report. AB - A hemophiliac child with flexion contracture of the knee and symptoms of leg length difference was treated with a shoe lift on the affected side, which failed to aid the problem. Further investigation revealed that the affected limb was actually longer than the contralateral side. The chronic synovitis of the knee that had resulted in the contracture also caused supplementary bone growth around the distal femoral epiphysis, resulting in the lengthening of that leg. PMID- 4028617 TI - Dose-dependent absorption of amoxycillin and bacampicillin. AB - The relationship between the relative absorption and increasing oral doses of amoxycillin and bacampicillin, a prodrug of ampicillin, was studied testing the hypothesis that a saturable transport system for aminopenicillins exists in the human gut. Each drug was given in four different doses in a randomized order to 12 fasting subjects. One group of subjects was given amoxycillin in single doses of 375, 750, 1500, and 3000 mg, while the other group received bacampicillin in 400, 800, 1600, and 3200 mg doses. The highest dose was four times larger than that normally used in clinical practice. Amoxycillin, and ampicillin generated from bacampicillin, were determined in plasma and urine by modern column liquid chromatographic methods. With increasing doses of the penicillins, there was a saturable increase in peak plasma concentration, plasma AUC, and urinary recovery. The mean (+/- SD) AUC values after 750, 1500, and 3000 mg amoxycillin were 86% +/- 13%, 70% +/- 16%, and 55% +/- 14% of that expected, when the expected ratio of AUC to dose was that of the 375 mg dose, assuming nonsaturable absorption. The corresponding AUC values after 800, 1600, and 3200 mg bacampicillin were 97% +/- 17%, 89% +/- 19%, and 76% +/- 11% of that expected from the results obtained after the 400 mg dose. The importance of dose of either drug for AUC and urinary recovery was analyzed according to a function implying capacity-limited absorption. The dose-dependency was most pronounced for amoxycillin (P less than 0.001). Renal drug clearance was stable within subjects throughout the dose range. Our results support the concept of capacity-limited absorption of aminopenicillins, probably by carrier-mediated transport. However, limited solubility of the compounds, especially of bacampicillin, may be a confounding factor. PMID- 4028618 TI - The pharmacokinetics of baclofen derived from intestinal infusion. AB - The pharmacokinetics of baclofen, a centrally acting muscle relaxant, have been elucidated in man. The pharmacokinetic disposition was determined form plasma concentration-time data and urinary recovery after the administration of rate limiting intestinal infusions and an oral bolus dose. Based on comparisons between the plasma concentration-time profiles from the intestinal infusions and the oral bolus doses, relative regression parameter assignments were made. The intestinal absorption of baclofen after intestinal infusion was very rapid, such that baclofen disposition was well characterized by an open two-compartment pharmacokinetic model with zero-order input. Intravenous administration of baclofen was precluded from this study because of the potential for severe adverse reactions. The average distribution phase constant (alpha) was 1.29 hours 1 and the average elimination phase constant (beta) was 0.191 hours-1. Average volume of the central compartment (Vc/F), volume of the body compartment (Varea/F), systemic clearance (CL/F), and renal clearance were 28.8 L, 59.0 L, 180 ml/min, and 103 ml/min, respectively. Pharmacokinetics were dose proportional in the dose range studied. The use of these pharmacokinetic parameters as determined in normal subjects in therapeutic management is particularly relevant, because baclofen is targeted to a patient population subject to renal dysfunction. PMID- 4028620 TI - Circulatory effects of intravenous and oral acebutolol in acute myocardial infarction. AB - The hemodynamic dose-response effects of intravenous (25 and 50 mg) and oral (200 and 400 mg) acebutolol were compared in a randomized between-group study in men within 17 hours of an acute uncomplicated myocardial infarction. Six subjects were evaluated in each of the four groups. After a 1-hour control period, hemodynamic variables and plasma drug concentrations were determined at 15 (intravenous therapy only), 30, 60, 90, 120, and 240 minutes after dosing. At the doses studied, hemodynamic dose-response effects were not evident after either intravenous or oral acebutolol. In all groups acebutolol reduced systolic and mean systemic arterial pressure, heart rate, cardiac output, and stroke volume. Pulmonary artery occluded pressure and systemic vascular resistance were transiently increased. Maximum changes developed between 15 and 30 minutes after intravenous dosing and between 1 and 2 hours after oral dosing. However, there were substantial reductions in cardiac output (-0.7 L/min/m2; P less than 0.05) by 30 minutes after oral dosing. Effects lasted for 2 hours after intravenous dosing and for 4 hours after oral dosing. Our data confirm the hemodynamic safety of acebutolol after acute myocardial infarction. The relevance of the time dependent hemodynamic differences between intravenous and oral initiation of beta blockade to the overall goal of reducing myocardial oxygen requirements after acute coronary artery occlusion merits closer examination. PMID- 4028619 TI - Sulindac is not renal sparing in man. AB - We investigated the claimed renal-sparing effect of the cyclooxygenase inhibitor sulindac. Fifteen normal women following a diet of 50 mEq salt a day were randomly assigned to 5 days of either placebo, sulindac, 200 mg b.i.d., or indomethacin, 25 mg q.i.d., after first serving as their own controls. Renal effects were assessed by the excretion rate of prostaglandin (PG) E2 (an index of renal PG synthesis), sodium balance, plasma renin activity (PRA), and the response to furosemide. Systemic effects were assessed by collagen-induced platelet aggregation and thromboxane B2 formation and by the urinary excretion of a systemically formed metabolite of PGF2 alpha (PGF-M). Both sulindac and indomethacin resulted in a positive sodium balance and a reduction in 24-hour urinary PGE2 excretion (range -49% to -86%). Basal PRA was decreased by indomethacin only, but the increases in PRA and in urinary PGE2 excretion in response to furosemide were inhibited by both sulindac and indomethacin. Sulindac reduced the natriuresis induced by furosemide, and indomethacin reduced the rise in inulin clearance after furosemide. Thus the two nonsteroidal anti-inflammatory drugs had similar effects on the kidney. Indomethacin had a greater effect than sulindac on the inhibition of collagen-induced platelet aggregation and thromboxane synthesis and the two drugs had equivalent effects on the reduction of PGF-M excretion. Peak plasma drug concentration of indomethacin (1.9 +/- 0.4 microgram/ml) and sulindac sulfide (7.7 +/- 1.9 microgram/ml) were those associated with clinical efficacy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4028622 TI - Pharmacokinetics of transdermally delivered clonidine. AB - We detail a series of pharmacokinetic investigations to determine the dose linearity, the effect of site of application, the duration of steady-state plasma concentrations, and the effect of chronic application when clonidine is administered transdermally. Dose linearity was assessed in six subjects with normotension after application of increasing sizes of transdermal clonidine systems (3.5, 7.0, and 10.5 cm2 size) to the upper outer arm. Of the six subjects studied, five had linear relationships between clonidine plasma concentrations at steady state and system size of greater than 0.975; in the sixth subject the correlation was greater than 0.90. The mean steady-state plasma concentrations with 3.5, 7.0, and 10.5 cm2 systems were 0.39, 0.84, and 1.12 ng/ml, respectively. The influence of site and duration of application on the absorption of transdermal clonidine was studied in eight subjects with normotension by use of the 3.5 cm2 system. The mean steady-state plasma concentration over the time interval from 3 to 7 days after application to the arm or to the chest did not significantly differ. When a system was left on the chest or arm for a total of 11 days (4 days beyond the recommended time to change systems), the plasma concentrations of seven of eight subjects with application to the arm and of six of eight subjects with application to the chest remained constant through day 11. The influence of consecutive applications of 3.5 cm2 transdermal clonidine systems on steady-state plasma clonidine concentrations was also studied in eight subjects with normotension over an 11-day period.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4028621 TI - Prostaglandins and nicotinate-provoked increase in cutaneous blood flow. AB - The mechanism of topically applied methyl nicotinate-induced local cutaneous erythema was studied in normal human subjects. Aqueous methyl nicotinate (0, 0.1, 1.0, 10.0, and 100 mmol/L) was applied to the volar forearms in quadruplicate after oral pretreatments with 25 mg doxepin hydrochloride, 600 mg ibuprofen, 50 mg indomethacin, 975 mg aspirin, and lactose placebo. The cutaneous vascular response was monitored by laser Doppler velocimetry. Although doxepin did not affect the cutaneous vascular response to methyl nicotinate, indomethacin, ibuprofen, and aspirin significantly suppressed the response. Because indomethacin, ibuprofen, and aspirin have different chemical structures, the common property of inhibition of the response to methyl nicotinate may be assigned to their common pharmacologic action, i.e., inhibition of prostaglandin bioformation. PMID- 4028623 TI - Pharmacokinetics of intravenous and intraperitoneal cefotaxime in chronic ambulatory peritoneal dialysis. AB - We investigated the kinetics of cefotaxime in eight subjects undergoing continuous ambulatory peritoneal dialysis (CAPD). A single 1 gm iv dose was injected and a 1 gm dose was given intraperitoneally in the CAPD fluid during a 4 hour dwell time. Cefotaxime and desacetylcefotaxime were assayed by HPLC. After intravenous injection the cefotaxime serum kinetic parameters were as follows: plasma t 1/2, 2.31 +/- 0.20 hours; volume of distribution, 0.35 +/- 0.04 L/kg; total plasma clearance, 118.7 +/- 12.3 ml/min; and peritoneal clearance, 6.7 +/- 1.3 ml/min. Dialysate cefotaxime concentrations rose rapidly, but only 5% of the dose was eliminated by the peritoneal route. After intraperitoneal instillation, cefotaxime appeared in the serum rapidly and the peak serum concentrations ranged from 9 to 20 micrograms/ml between 1 and 3 hours. The absorption of cefotaxime from peritoneal space was 58.7% +/- 5.4%. Data suggest that cefotaxime has bidirectional exchange characteristics through the peritoneal membrane. Instillation of cefotaxime in CAPD fluid may permit rapid absorption to achieve therapeutic serum concentrations. PMID- 4028624 TI - A new dosing regimen in renal insufficiency: application to cephalexin. AB - We describe a new method of drug dosage adjustment. The method simultaneously considers glomerular and tubular functions as parameters, because nonparallel decreases in both functions limit the use of the conventional endogenous creatinine clearance (CLCR) method for dosage adjustment. In the new method, CLCR and the 15-minute phenolsulfonphthalein (PSP15') test were used and applied to patients with renal insufficiency with cephalexin (CEX) as a model drug for renal tubular secretion. The results clearly demonstrate good control of plasma CEX concentrations by the CLCR-PSP15' method, whereas there were marked changes in plasma CEX levels with the CLCR method alone. Our method appears to be more useful for patients with renal impairment than the conventional CLCR method for CEX, which is mainly excreted in urine by renal tubular secretion. A nomogram for the CEX dosing interval is proposed for application to clinical practice. PMID- 4028625 TI - Influence of transdermal scopolamine on motion sickness during 7 days' exposure to heavy seas. AB - We conducted a double-blind, placebo-controlled study to evaluate the efficacy and tolerability of transdermal scopolamine in the prevention of motion sickness (MS) aboard a frigate during 7 days of continuously moderate or heavy seas. Forty nine healthy sailors with a previous history of MS were randomly assigned to receive a transdermal therapeutic system of scopolamine (TTS-S) or transdermal placebo (TD-P). Patches were placed behind the ears at least 4 hours before departure and were removed 72 hours later. Subjects were observed on days 1 to 4 and 6. In the TTS-S group, both subjective feeling of MS and the incidence of nausea were reduced during the first 2 days. Because of adaptation, differences in signs and symptoms of MS between subjects receiving TTS-S and TD-P disappeared after the second day. During the first 3 days, vomiting occurred less often in the TTS-S group. On day 6, 3 days after removal of the patch, vomiting occurred in 23% of the TTS-S group, probably due to delay in adaptation, but none of the subjects in the TD-P group vomited. Concentration was not adversely influenced, since the ability to work increased in the TTS-S group. During prolonged continuous exposure to heavy and moderate seas, 2.5 cm2 TTS-S discs proved to be efficacious in preventing MS, with xerostomia as a tolerable side effect and no significant ocular side effects. PMID- 4028626 TI - Oral triamterene disposition. AB - Earlier studies of triamterene (T) disposition in man have reported hydroxytriamterene (T-OH) and hydroxytriamterene sulfate (T-O-SO3H) conjugate to be the major metabolites. We describe T kinetics through use of an HPLC method and confirm that after hydroxylation, T is rapidly converted to T-O-SO3H. The intermediate T-OH metabolite could not be detected in urine or plasma. Plasma concentrations of T-O-SO3H exceeded those of T by sevenfold to 26-fold, whereas concentrations of that metabolite in the urine were fourfold to thirteenfold higher than those of the parent. Renal clearance of T was 314.5 +/- 121.6 ml/min, exceeding that of the metabolite, which was 206.1 +/- 93.6 ml/min. Coadministration of hydrochlorothiazide increased urine flow and urinary pH, but it did not affect renal clearance of the parent drug or the metabolite. T bioavailability from capsules was poorer and more variable than that from a suspension. Hydrochlorothiazide did not influence the bioavailability of T. PMID- 4028627 TI - Controlled trial of acifran in type II hyperlipoproteinemia. AB - The hypolipidemic effects of acifran were evaluated in a randomized, double blind, placebo-controlled study of 30 patients with type IIa hyperlipoproteinemia. Plasma lipid and lipoprotein values were determined at baseline (mean of three values), again after a 2-week single-blind period of acifran dosing, and at 2-week intervals during a 10-week period of double-blind drug dosing. At week 8, subjects who received the lower dose of acifran (100 mg t.i.d.) showed significantly lower levels of total and low-density lipoprotein cholesterol and triglycerides compared with their baseline levels (P less than 0.01) or the placebo group (P less than 0.05). At week 12, subjects who received the higher dose of acifran (300 mg t.i.d.) had an increase in high-density lipoprotein levels of 16% (P less than 0.01) and a decrease in the ratio of low- to high-density lipoproteins of 22% compared with their baseline levels (P less than 0.01). There were no significant differences in lipid responses between the two groups receiving acifran. Transient mild flushing and pruritus were experienced by some subjects, but no subject failed to complete the study because of drug intolerance or side effects. The safety and efficacy demonstrated in this short-term therapeutic trial justify additional long-term studies with acifran. PMID- 4028628 TI - Kinetics of cocaine distribution, elimination, and chronotropic effects. AB - The pharmacokinetics of cocaine were studied in five subjects with histories of drug abuse who were otherwise healthy. A two-compartment system was used to model the distribution kinetics of the drug. The steady-state volume of distribution averaged 131.8 L or 1.96 L/kg, elimination clearance was 2.10 L/min, and the t 1/2 was 48 minutes. Cocaine concentrations in a hypothetic biophase were estimated to correlate the chronotropic effects of this drug with its pharmacokinetics. The experimentally determined kinetic parameters indicate that the peak chronotropic effect would occur 7.3 minutes after intravenous bolus injection of cocaine, and that biophase cocaine concentrations would initially accelerate the heart rate by 0.3 bpm for each 1 ng/ml. The kinetic analysis also demonstrated that the chronotropic effects of cocaine decline more rapidly than either plasma levels or biophase concentrations. This progressive attenuation in intensity of the chronotropic effect of a given biophase cocaine concentration could be modeled as a first-order process and is compatible with either the intervention of homeostatic reflex mechanisms or the phenomenon of acute tolerance. PMID- 4028629 TI - Gastrointestinal absorption as a function of age: xylose absorption in healthy adults. AB - Xylose oral absorption was examined in 24 healthy male subjects ranging in age from 32 to 85 years. Absorption was evaluated from xylose plasma concentration time data after administration of a 25 gm po or a 5 gm iv dose. There was no relationship between various estimates of the rate of absorption and age. The absolute oral bioavailability or the extent of xylose absorption showed no relationship to age in our population. In contrast with previous suggestions, xylose absorption does not decline with age. General statements of decreased gastrointestinal absorption efficiency as a function of age may not be correct. PMID- 4028630 TI - Efficacy of clonidine and of methadone in the rapid detoxification of patients dependent on heroin. AB - The efficacy of a rapid detoxification schedule (8 to 10 days) with clonidine or methadone was evaluated in 30 patients addicted to heroin. The dose of study drug was preestablished according to the subject's weight and the amount of opioid consumption, and the total daily dose was reduced by approximately 15% during the study. All subjects completed the detoxification program and stayed in the hospital for at least 12 days. Clonidine and methadone therapies proved to be highly effective. There was a marked reduction in anxiety during opioid detoxification, although subjects' experiences differed according to the drug used. On the day of discharge, subjects who had received methadone still had attenuated withdrawal symptoms, whereas there were no such symptoms in the clonidine group. Muscular aching, flatulence, and daily drowsiness were more common among subjects in the methadone group, while subjects in the clonidine group had more sleep disturbances and weeping. Syncopal episodes and bradycardia occurred more frequently in the clonidine group. PMID- 4028631 TI - Lack of interaction between verapamil and cimetidine. AB - Nine healthy normal subjects received verapamil, 10 mg iv, before (control) and during cimetidine dosing (300 mg every 6 hours), and verapamil, 120 mg po, twice in the same manner. After intravenous doses, the t1/2 (means +/- SE: control, 3.60 +/- 0.40 hours; cimetidine trial, 4.30 +/- 0.60 hours), volume of distribution (5.8 +/- 0.6 vs. 6.6 +/- 0.9 L/kg), and total clearance (19.2 +/- 1.5 vs. 18.4 +/- 1.6 ml/min/kg) did not change during cimetidine dosing. After oral doses, the t1/2 (4.25 +/- 0.57 vs. 4.60 +/- 0.70 hours), plasma AUC (585 +/- 113 vs. 506 +/- 82 ng/ml X hr) and absolute bioavailability (35% +/- 7% vs. 30% +/- 5%) did not differ between control and cimetidine trials, respectively. Five of the subjects also received lidocaine, 25 mg iv, once in the control state and once during the cimetidine regimen described above. Lidocaine clearance fell (665 +/- 216 vs. 527 +/- 134 ml/min; P less than 0.05) during cimetidine therapy, resulting in a trend toward a longer t1/2 (1.81 +/- 0.41 vs. 2.44 +/- 0.42 hours; 0.1 greater than P greater than 0.05) with no change in volume of distribution (1.77 +/- 0.66 vs. 1.99 +/- 0.81 L/kg). Verapamil pharmacodynamics (ECG PR interval, blood pressure, and heart rate) were evaluated after intravenous doses. A decrease in mean arterial pressure (8 +/- 1 vs. 9 +/- 2 mm Hg) and a reflex increase in heart rate (14 +/- 3 vs. 17 +/- 2 bpm) were no different in the control and cimetidine trials.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4028633 TI - Conceptual model for allocation and rationing physical health services to Colorado's medically indigent. PMID- 4028634 TI - Conceptual model for allocation and rationing physical health services to Colorado's medically indigent. Part Two: Facts and assumptions/goals and objectives. PMID- 4028632 TI - Lack of effect of oral activated charcoal on imipramine clearance. AB - The effect of oral activated charcoal on the pharmacokinetics of intravenous imipramine was studied in a randomized, crossover trial. Four normal men received intravenous imipramine (12.5 mg/70 kg) on two separate occasions, followed by either water or water plus high-surface-area activated charcoal (180 gm) in divided doses over 24 hours. Serum imipramine concentrations were measured from 0 to 24 hours after the imipramine infusion. There was no difference in the mean (+/- SE) t1/2 (9.0 +/- 0.8 vs. 10.9 +/- 1.6 hours), apparent volume of distribution (11.2 +/- 2.1 vs. 12.4 +/- 2.1 L/kg), or systemic clearance (992.2 +/- 138.3 vs. 930.3 +/- 101.9 ml/min/70 kg) of imipramine after dosing without and with oral activated charcoal, respectively (P greater than 0.05; paired t test). These results suggest that multiple oral doses of activated charcoal do not increase the clearance of imipramine in man. PMID- 4028636 TI - Biochemistry of exercise. 6th international symposium, June 12-15th, 1985 Copenhagen, Denmark. Abstracts. PMID- 4028637 TI - [Neuroses and their socio-cultural aspects. Therapeutic prospects]. PMID- 4028635 TI - How to draw up your living will. PMID- 4028638 TI - [Efficacy and tolerability of a new chemotherapeutic agent in the treatment of recurrent chronic bronchitis: xibornol]. PMID- 4028639 TI - [Efficacy of treatment with hydroalcoholic solutions of nifedipine in various cardiovascular emergencies]. PMID- 4028640 TI - [Malabsorption syndrome secondary to celiac disease in an adult. Presentation of a case]. PMID- 4028641 TI - [Medical therapy of gastric carcinoma]. PMID- 4028642 TI - [The laser in medicine: an instrument of precision and great versatility]. PMID- 4028643 TI - [From information to meaning: its features and clinical methodology]. PMID- 4028644 TI - [Carpal tunnel syndrome: therapeutic considerations]. PMID- 4028645 TI - [Calcitonin in the treatment of algodystrophic syndromes]. PMID- 4028646 TI - [Pregnancy in the patient under chronic hemodialysis treatment. Our clinical experience]. PMID- 4028647 TI - [Evaluation of the hypotensive efficacy in a double-blind study of xipamide versus chlorthalidone]. PMID- 4028648 TI - [Unusual development of visceral leishmaniasis. Considerations apropos of a case]. PMID- 4028649 TI - [Sleep]. PMID- 4028650 TI - [Rehabilitation of stage II peripheral arteriopathies]. PMID- 4028652 TI - [Effects of the administration of exogenous calcitonin in dialysis patients. Preliminary study]. PMID- 4028651 TI - [Evaluation of the symptomatic clinical efficacy of ranitidine in benign gastroduodenal pathology]. PMID- 4028653 TI - [Effects of D(+)-bis-(N-pantothenyl-amidoethyl)-disulphur on the blood lipid profile and apoproteins A and B levels]. PMID- 4028654 TI - [Current methods in the medico-legal verification of acoustic injuries]. PMID- 4028655 TI - [Diagnostic and etiopathogenetic aspects of dilated cardiomyopathy. Discussion of a case]. PMID- 4028656 TI - Symposium on body fluid analysis. PMID- 4028657 TI - Approach to the analysis of body fluids for the detection of infection. AB - Sterile body fluids represent an important source for the diagnosis of infectious diseases because they can be sampled by sterile methods that bypass the normal bacterial flora so heavily colonizing the body surface. Thus when these specimens are received, full advantage should be taken to perform complete microscopic and cultural tests for viral, bacterial, mycobacterial, fungal, and parasitic diseases. In many cases the evaluation can be tailored to the types of organisms that are likely to infect particular body cavities. Ideally, the workup could also be based on the history, clinical presentation, and preliminary examination of the patient, but under most circumstances it may be more appropriate for the laboratory to proceed with a more complete workup of these vital specimens than physicians request. Specimens should be transported promptly to the laboratory and should be viewed quickly by Gram's or acridine orange stain and, in selected situations, also by acid-fast stain, direct fluorescence for legionellosis, and direct wet mount for parasites. Results of these studies should be called in without delay to the responsible physician. Cultures should also be inoculated as soon as possible. Nonspecific tests, including the cell count and protein, glucose, lactic acid, and LDH levels, may provide valuable clues to the presence of infection. Direct antigen detection does not replace traditional microscopic and cultural evaluation of these specimens but may have supplemental value. PMID- 4028658 TI - The identification of fungal casts. A new method for diagnosing visceral candidiasis. AB - Visceral candidiasis is a potentially life-threatening infection that is difficult to diagnose clinically. Existing laboratory methods do not adequately distinguish visceral candidiasis from extensive candidal infections of mucosal surfaces. A new laboratory method, the detection of fungal casts in urine sediment, permits the unequivocal diagnosis of renal candidiasis. Since the severity of renal candidiasis varies, the clinical significance attributed to the identification of fungal casts in the urine must be based upon a complete assessment of the patient. The ultimate utility of the fungal cast method will depend upon the incidence with which fungal casts can be identified in the urine of patients with renal candidiasis. At present, this incidence is unknown. However, the method has been clinically useful in a number of specific cases and should not be overlooked in evaluating patients with candiduria in whom the diagnosis of visceral candidiasis is suspected but not confirmed. PMID- 4028659 TI - Laboratory diagnosis of male infertility. AB - Male infertility is best tested by determining the ability of sperm to reach the site of fertilization by semen analysis and by mucus-sperm interaction tests, and by determining the ability of the sperm to enter the egg by the hamster egg-human sperm penetration assay. If conducted in a careful fashion, the tests provide useful information for preparing a treatment plan. PMID- 4028660 TI - Cell wall deficient organisms--the Microbial Chameleons Seminar presented at the 84th annual meeting of the American Society for Microbiology. St. Louis, Missouri, March 6, 1984. PMID- 4028661 TI - Mycoplasmas as a tool for membrane research. PMID- 4028662 TI - Evidence for the bacterial origin of Acholeplasma laidlawii A. AB - L-forms from a Corynebacterium were induced in hyperosmolar media and gradually adapted to normal osmolarity over a period of two years. During this adaptation several morphologic L-form variants derived from the L-form cultures and were serologically identified as Acholeplasma laidlawii A. The possibility that the bacterial and L-form cultures were contaminated with acholeplasmas was carefully investigated; this was determined not to be the case. Membrane protein gel electrophoresis patterns of these L-form variants were identical to the ATCC A. laidlawii strain PG-8. Acholeplasma phage MVL-1 displayed no affinity for these L form variants. Phage MVL-2 showed low affinity, but after virus enhancement in the specific host, high plaquing efficiency ensued. DNA hybridization experiments showed a high level of nucleotide sequence homology (greater than 90%) between the L-form-derived variants and PG-8. The homology between the diphtheroid L forms and the PG-8 strain was 16.4% with te50 values of 86%; this indicates strong base pairing homology. These findings suggest that the L-form variants are acholeplasmas and that they are biologically and genetically related to the Corynebacterium L-forms. PMID- 4028663 TI - Ureaplasma urealyticum: subcultures invalid for antibiotic susceptibility tests. AB - We tested the antibiotic susceptibilities of 100 Ureaplasma urealyticum strains from 99 patients using a broth-disk method and two types of inocula: urine sediments and overnight broth subcultures of the sediments. Of the 100 ureaplasma positive urine sediments tested, nine (9%) of the ureaplasmas were found resistant to all four tetracyclines. When overnight broth cultures were used as the inoculum, 54 (54%) were found to be resistant to all four tetracyclines, an increase in resistance of 45 (45%). Thirty-seven susceptible strains remained susceptible upon subculture. The nine resistant strains remained resistant. Loss of susceptibility was not related to the pH or titer of ureaplasmas in the urine sediment inoculum but was related to the pH and titers when subcultures were used as the inoculum. Results of cultures following treatment, available for 53 patients, showed that treatment successes and treatment failures were significantly related to antibiotic susceptibility tests done with urine sediments but not to those done with broth subcultures as the inocula. Because reliable susceptibility testing is essential for appropriate therapy for U. urealyticum infections, all factors influencing this test need to be recognized and defined. PMID- 4028664 TI - Peritonitis involving Capnocytophaga ochracea. AB - Spontaneous bacterial peritonitis, due to Capnocytophaga ochracea, developed in a 65-year-old alcoholic patient with extensive cirrhosis and ascites. Previously reported human infections with this organism have included peridontal diseases, septicemia, and arthritis. This is the first report of spontaneous bacterial peritonitis associated with Capnocytophaga species. PMID- 4028665 TI - Isospora infection in a homosexual man. AB - A case of Isospora belli in a homosexual male is described. The procedures used for recovery and staining the cyst stages of Isospora are included. PMID- 4028666 TI - A plea for the preservation of opportunistic fungal isolates. PMID- 4028667 TI - Community-wide surveillance of Campylobacter jejuni infection. Evaluation of a laboratory-based method. AB - Surveillance of infections due to Campylobacter jejuni is needed to further define the epidemiology of this disease in the U.S. We assessed one potential method of community-wide surveillance, a laboratory-based reporting network. Six microbiology laboratories that routinely culture fecal specimens for C. jejuni reported all isolates to Seattle-King County Health Department for an 18-month period. Further investigations on 476 cases reported from this broadly based network revealed that C. jejuni enteritis affected primarily children and young adults, occurred sporadically (with a summer-fall predominance), led to hospitalization in 13% of cases, was found negligibly in patients hospitalized or immunocompromised, and produced no fatalities. Comparative statistics showed that C. jejuni was reported more frequently than Salmonella and Shigella combined in individuals served by reporting laboratories. Because one participating laboratory was that of a 280,000-member health maintenance organization, it was possible to calculate age-specific incidence rates for bacterial enteric infections in that population. C. jejuni and Salmonella had high attack rates among 0-4 year-old children: 184 cases/100,000 enrollees per year and 126/100,000 per year, respectively. C. jejuni showed another peak at 20-29 years (108/100,000 per year) that was absent in salmonellosis. This study demonstrates that a laboratory-based reporting system is a feasible approach to community-wide C. jejuni surveillance. PMID- 4028668 TI - Staphylococci, in vitro and in vivo. AB - Strains of Staphylococcus aureus were grown in broth and by the membrane technique; both drug-free media and media containing cloxacillin were used. The staphylococci grown in broth containing cloxacillin showed one thick cross wall and were larger than those grown in drug-free broth: 1.6 micron in diameter as opposed to 0.9 micron. The staphylococci grown on membranes placed on agar containing cloxacillin were 2-3 microns in diameter and contained three or more cross walls. Mice were infected intraperitoneally with staphylococci. After treatment with cloxacillin, the peritoneal fluid and spleens contained staphylococci that were 2-3 microns in diameter with three or more cross walls. A staphylococcal endocarditis was induced in rabbits that were then treated with cloxacillin. The staphylococci in the vegetation of the treated rabbits were 2-3 microns in diameter and contained multiple cross walls. Large staphylococci with multiple cross walls were observed in specimens from patients with respiratory infections treated with beta-lactam antibiotics. It appears, therefore, that the ultrastructure of staphylococci in vivo is comparable to that of staphylococci grown on a solid support medium such as a membrane, and different from that of staphylococci grown in a liquid medium. PMID- 4028669 TI - Rupture of vascular prosthesis in a patient with Yersinia enterocolitica bacteremia. AB - A case of bacteremia caused by Yersinia enterocolitica serotype 3, biotype 4, is described in a 79-year-old man with an aortic bifurcation prosthesis. He died, in spite of antibiotics, from massive intraabdominal bleeding at the infected suture site. Yersinia, like Salmonella, seems to have a special affinity for damaged endovascular tissue, although more observations will be needed to support this hypothesis. PMID- 4028670 TI - Classification of depression. PMID- 4028671 TI - Decision making in the treatment of depression by family medicine physicians. PMID- 4028672 TI - The diagnosis of multiple personality syndromes: overt, covert, and latent. PMID- 4028673 TI - The diagnosis and treatment of psychiatric emergencies. AB - Although the majority of psychiatric patients present to the ER in chronic crisis, the clinician should also be familiar with the assessment and management of acute emergencies. Because emergency patients reflect the entire spectrum of psychiatric psychopathology, the primary care physician should consult with a mental health clinician whenever possible. Following a medical model, a thorough diagnostic evaluation should be completed and specific treatment initiated. Most often, the treatment consists of some combination of psychological, pharmacologic, and physical approaches. PMID- 4028674 TI - The Agent Orange controversy in Australia: a contribution to the debate. PMID- 4028675 TI - The feasibility of ascertaining exposure to pesticides by self report in Australian Vietnam veterans. PMID- 4028676 TI - Behaviourally-based principles as guidelines for health promotion. PMID- 4028677 TI - Setting occupational health standards in Australia: the case of screen-based equipment operators' eyesight tests. PMID- 4028678 TI - The weight of knowledge: teachers and students and doctors and patients. PMID- 4028679 TI - 'Does the mode matter?'--A comparison of three modes of questionnaire completion. PMID- 4028680 TI - Social status and morbidity in Australia. PMID- 4028681 TI - Evidence for a rate-limiting role of cysteinesulfinate decarboxylase activity in taurine biosynthesis in vivo. AB - The relationship between activities of enzymes involved in cysteine oxidation and the apparent conversion of cysteine to taurine in vivo were investigated in the rat and cat. Both hepatic cysteinesulfinate decarboxylase activity and the oxidation in vivo of cysteine to taurine were lower in the kitten than in the adult female rat and lower in the latter than in the young male rat. Our data support the hypothesis that cysteinesulfinate decarboxylase plays a rate-limiting role in taurine biosynthesis. PMID- 4028682 TI - Erythrocyte acid phosphatase: species specificity in activity modulation by purine analogs. AB - The previous studies of the interaction of purine analogs and human erythrocyte acid phosphatase isozymes were extended to include erythrocyte acid phosphatase from seven other species. Consistent responses, similar to the observations with the several genotypically different human isozymes, were observed. The isozyme from chimpanzee erythrocytes was similar to the human B-type isozyme while the baboon and cow isozymes were at the other extreme in responsiveness and were more divergent from the B-isozyme than was the human A-type isozyme. The ACP from rabbit, dog, sheep and rhesus erythrocytes exhibited intermediate levels of responsiveness but did differ from the human A-type isozyme. Additional studies indicated some differences between the responsiveness of the partially purified erythrocyte enzyme and the low molecular weight ACP from liver. PMID- 4028684 TI - Hybrid protein synthetic systems: components required to confer poikilothermy to the mammal. AB - Temperature dependency of homologous and heterologous protein synthetic cell-free systems reveals characteristic homeotherm and poikilotherm behavior depending on the source of the enzyme elongation factor 1 and not on any other protein synthetic components. The results for rat and Antarctic fish, when compared with previous studies in eurythermal fish and mammals provide the explanation for the phenomenon of true hibernation in animals such as ground squirrels and woodchucks. The killing of these rare animals can now be stopped by granting agencies that support hibernation research. Comparison of temperature effects on laboratory rats and wild rats indicate a need for wild rat research directed toward eradication of these pests in cities. Suggestions are made for this purpose. PMID- 4028683 TI - Inhibition by potential metabolic inhibitors of in vitro adipose tissue lipogenesis. AB - To study the pathway of lactate utilization as a carbon source for fatty acid synthesis, the effect of (-)-hydroxycitrate, agaric acid, sodium oxamate, 2-n butyl malonate and alpha-cyano-4-hydroxycinnamate on the rate of in vitro conversion of lactate, acetate and glucose to fatty acids was measured in bovine and rat adipose tissues. Sodium oxamate and hydroxycitrate caused less fatty acid to be synthesized from lactate in bovine adipose tissue. Hydroxycitrate depressed fatty acid synthesis from glucose in rat adipose tissue. alpha-Cyano-4 hydroxycinnamate was an effective inhibitor of lipogenesis from all substrates and may act as a specific inhibitor in adipose tissue. Although the inhibitors were absorbed poorly into adipocytes, the results indicate that conversion of lactate to fatty acids probably occurs by way of the citrate cleavage pathway. PMID- 4028685 TI - Lactate dehydrogenase isozymes and allozymes of the nine-spined stickleback Pungitius pungitius (L.) (Osteichthyes: Gasterosteidae). AB - Zymograms indicate the existence of three loci coding for lactate dehydrogenase in the nine-spined stickleback Pungitius pungitius. The skeletal muscle locus is polymorphic for two codominant alleles: Ldh-A(100). and Ldh-A(140). Differences in allele frequencies among nine samples, obtained from eight geographically isolated populations, proved not significant in 28/36 pairwise comparisons. The frequency of Ldh-A(100) varied from 0.426 to 0.715. Significant differences in apparent Km (pyruvate) values were found among the LDH-A allozymes suggesting a functional basis for the selective maintenance of this polymorphism. PMID- 4028686 TI - Study on a special binding phenomenon of biliverdin in the blood of the eel, Anguilla japonica. AB - Biliverdin is bound firmly with a plasma protein in the blood of the eel, Anguilla japonica. The firm binding, although likely noncovalent, could be formed only in vivo under the experimental conditions. Characterization of the carrier protein indicated that it is a serum albumin. A similar phenomenon is not detectable in ten other fish species examined in this study. PMID- 4028687 TI - Cytoplasmic NADP-linked dehydrogenase activities in avian tissues. AB - Cytoplasmic activities of NADP-linked malic enzyme (E.C. 1.1.1.40), glucose-6 phosphate dehydrogenase (E.C. 1.1.1.49) and NADP-linked isocitrate dehydrogenase (E.C. 1.1.1.42) were determined in tissues of selected avian species, and compared with those in mammals. Malic enzyme was generally more active in avian liver and kidney than in the corresponding mammalian tissues. Hepatic activities as high as 200 units/g wet wt and 100 units/g wet wt were recorded in the Nectariniidae and the Ploceidae respectively. Glucose-6-phosphate dehydrogenase was generally less active in avian tissues than malic enzyme. In passerine birds activities were very low indeed, and in most cases spectrophotometrically undetectable. Malic enzyme and glucose-6-phosphate dehydrogenase were highly active in the adipose tissue of mammals but were inactive in the adipose tissue of birds. Marked increases in hepatic malic enzyme and glucose-6-phosphate dehydrogenase activities were associated in birds with premigratory fattening. Activities of isocitrate dehydrogenase were comparable in the corresponding avian and mammalian tissues, including adipose tissue. PMID- 4028688 TI - Alterations in rat lipid metabolism following ecdysterone treatment. AB - The influence of ecdysterone on the lipid metabolism in liver and adipose tissue from rat was investigated using 14C-acetate and 32P-orthophosphate as precursors. Ecdysterone produced an increase in 14C-acetate incorporation into triglycerides. A concomitant decrease in free fatty acids and diglycerides was observed. The effect of ecdysterone on triglyceride lipase activity was investigated and a significant decrease was found. Ecdysterone produced a significant increase in the specific activity of phosphatidylethanolamine and phosphatidylserine in liver. On the contrary, the specific activity of phosphatidylcholine was reduced. In adipose tissue, the most evident effect observed was the increase of specific activity of phosphatidylcholine. These results contribute to knowledge of the heterophylic action of ecdysterone. PMID- 4028689 TI - Quantification of unscheduled DNA synthesis in mononuclear leukocytes of the horse. AB - This study compares the relationship between N-acetoxy-2-acetylaminofluorene (NA AAF) and u.v. induced unscheduled DNA synthesis (UDS) and their respective relationships to age and blood pressure in horse mononuclear leukocytes with earlier, similar investigations on human leukocytes. U.v. induced UDS was found to proceed more rapidly than NA-AAF induced UDS. A pronounced lag period associated with the rapid demand for 3H-dThd into DNA after u.v. damage was observed. NA-AAF induced UDS correlated significantly with NA-AAF binding, age and the blood pressure of male horses. UDS values, induced by either method, were about half the level calculated for human leukocytes. PMID- 4028690 TI - Microprocessor-based system for on-line analysis of respiratory responses to exercise. AB - A microprocessor-based system was developed for the measurement and on-line calculation of values and derivatives of expiratory variables and their response to exercise. The system accepts analog signals from gas analysers, ECG electrodes and flow transducer, digitizes these signals, calculates values of required parameters and presents results on a video display. The system offers the user various options of logging and data processing. Plots of the values of calculated parameters versus exercise time and correlation between variables can be easily produced by the system. A mass storage unit was available with the system to enable the storage of calculated variables for off-line analysis. Hardcopy of displayed results and plots can be provided by the system. PMID- 4028692 TI - Classification of depression. PMID- 4028691 TI - Delusional parasitosis and physical disease. PMID- 4028693 TI - Psychiatric diagnosis and competency to stand trial. PMID- 4028694 TI - A review of the research on conjugal bereavement: impact on health and efficacy of intervention. PMID- 4028696 TI - Stress, coping resources and psychiatric disorders: alternative paradigms from a life cycle perspective. PMID- 4028695 TI - 14-year follow-up of borderline and schizotypal personality disorders. PMID- 4028697 TI - Episodic behavioral disorders and limbic ictus. PMID- 4028698 TI - Electroconvulsive therapy and the elderly. PMID- 4028699 TI - Contact dermatitis in Nigeria. AB - Nickel is the most important sensitizer in Lagos, with an incidence of 12.3% of 453 patients tested. There was no sex difference, as the wearing of necklaces and bracelets was equally fashionable among both sexes. Housewife eczema is not common, probably because of hardening. Dermatitis from additives in the processing of leather and rubber footwear was the next most common. Chromate sensitivity comes usually from leather or cement. Cultural and climatic factors are mainly responsible for differences in the incidence of contact dermatitis found in Lagos from other countries. PMID- 4028700 TI - Nickel penetration in allergic individuals: bioavailability versus X-ray microanalysis detection. AB - Development of local allergic reactions after different application times with Finn Chambers was recorded in 34 nickel-sensitive patients. Biologically significant amounts of nickel seemed to penetrate the skin within a few hours, although physical penetration was minimal. Nickel was detected only in the upper keratin cell layer with an X-ray microanalysis method. PMID- 4028701 TI - Experimental nickel sensitization in the guinea pig: comparison of different protocols. AB - 3 different sensitization protocols were compared for inducing delayed-type nickel contact hypersensitivity in guinea pigs. Open epicutaneous sensitization (OE) induced nickel allergy in 11/22 (50%) guinea pigs. When intradermal injections of Freund's complete adjuvant into the nickel-painted skin was added to the same protocol, 4/13 (31%) became sensitized. The guinea pig maximization protocol induced nickel allergy in only 7/31 (23%) of the animals. Compared with the 2 other methods, animals sensitized with open epicutaneous applications reacted more rapidly (maximum at 6 h) and strongly (2+ reaction in 12/22 of animals) in previous patch test sites upon systemic (i.p.) nickel challenge. Open epicutaneous sensitization of guinea pigs should be a useful model for studying cellular and immunological mechanisms in nickel contact sensitivity. PMID- 4028702 TI - Allergic contact dermatitis to some medicaments. AB - Over the years, changes have had to be made in the list of topical drugs most frequently responsible for allergic contact dermatitis. The 4 most common sensitizers in Italy in the past have been penicillin, sulfonamide, promethazine and neomycin. Now the list is headed by neomycin, benzocaine and ethylenediamine. Antihistamines and parabens are less frequently observed as sensitizers. The increasing topical use of new drugs and additives, as well as older sensitizers, produces reactions to other substances, such as non-steroidal anti-inflammatory agents, some antimycotic drugs, propylene glycol and benzoyl peroxide. PMID- 4028703 TI - Reduction of intake of balsams in patients sensitive to balsam of Peru. AB - 64 patients participated in this study. 24 were patients who had positive patch tests to balsam of Peru. The dermatitis of 9 of the patients had flared after open oral challenge with balsam of Peru, and the dermatitis of 31 patients had flared after double-blind oral challenge. All 64 patients were asked to avoid food items suspected of containing balsams for 1 to 2 months. At the end of that time, an evaluation of the diet trial was made; the dermatitis of 37 had cleared or improved markedly. If an improvement had taken place, the patient was asked to continue to diet moderately. 6 months to 3 years after the diet was initiated, a questionnaire was mailed to those patients whose dermatitis had improved after the first trial. The patients were asked to evaluate the long-term benefit of following the diet. 30 felt there was a long-term effect, and 27 still followed the diet instructions to some degree. PMID- 4028704 TI - Allergic contact dermatitis to epoxy resin in infusion sets of an insulin pump. PMID- 4028705 TI - Ginkgo tree dermatitis. PMID- 4028706 TI - Contact urticaria to DNCB. PMID- 4028707 TI - Contact dermatitis from ibuprofen. PMID- 4028708 TI - Anesthetic considerations for geriatric patients. PMID- 4028709 TI - Abdominal aortic aneurysm resection: a ten-year community hospital experience. PMID- 4028710 TI - Neuromuscular and mental manifestations of hyperparathyroidism in the elderly. PMID- 4028711 TI - Practice variations in the provision of health care services. American Medical Association. PMID- 4028712 TI - Consensus development summaries. Travelers' diarrhea. National Institutes of Health. PMID- 4028713 TI - Recent trends in medical professional liability. AMA Center for Health Policy Research. PMID- 4028714 TI - A medical helicopter transportation system for Connecticut. PMID- 4028715 TI - Bilateral postpartum femoral neuropathy. PMID- 4028716 TI - Continuous passive motion (C.P.M.) following total knee replacement. PMID- 4028717 TI - Why adolescent medicine? More illustrative cases. PMID- 4028718 TI - Reflections on medicine. Rights and obligations. PMID- 4028719 TI - Decisions at the end of life: the legacy of Karen Ann Quinlan. PMID- 4028720 TI - Immune complexes and human cancer. PMID- 4028721 TI - Immune complexes in patients bearing solid tumors. PMID- 4028722 TI - Suppression of leukocytosis by the intrauterine delivery of high doses of indomethacin in the rat. AB - Studies were undertaken in rats to determine the intrauterine rate of release of high doses of indomethacin incorporated into Silastic rods. It was found that at a 28% w/w loading an 1X0.1 cm rod would exponentially deliver the drug at an average of 35 micrograms/day for the first 2 weeks; by 70 days the rate had declined to 6.5 microgram/day. After being present for 31 days, these types of medicated rods were found to reduce the numbers of luminal leukocytes when compared with the numbers obtained from uterine horns containing plain, non medicated rods. Despite the reduction in leukocytosis, implantation was prevented by the high dose of indomethacin. PMID- 4028724 TI - Post-abortion insertion of MLCu 250 and MLCu 375--a comparative trial. AB - This randomized prospective trial compared the use effectiveness and side effects of the MLCu 250 and MLCu 375 inserted immediately post-abortion. Five-hundred-and forty-nine patients were followed-up over a two-year period involving 9890 woman months of use with a loss to follow-up rate of only 5.1%. Both IUDs gave good protection against pregnancy (gross rates at 24 months, 1.8 and 2.1). There were no significant differences between the two devices in pregnancies or other termination events. PMID- 4028723 TI - Pharmacokinetic and pharmacodynamic investigations with monthly injectable contraceptive preparations. AB - Eight normally menstruating women received Cycloprovera (25 mg medroxyprogesterone acetate with 5 mg estradiol cypionate) and seven other volunteers received HRP-102 (50 mg norethisterone enanthate with 5 mg estradiol valerate) injections at 30-day intervals for three consecutive months. The peripheral plasma levels of estradiol (E2), progesterone (PROG), medroxyprogesterone acetate (MPA) and norethisterone (NET) were measured in the luteal phase of a pretreatment cycle, during the third treatment month and during a subsequent recovery period of 60 days. Blood samples were drawn three times a week (Mondays, Wednesdays and Fridays) and endometrial biopsies were taken on day 20 to 26 of the pretreatment cycle, 20 to 24 days after the last injection and 20 to 24 days after the first normal menstrual-like bleeding during the recovery period. The (geometric) mean maximum level of MPA was 2.9 (2.4-3.7) nmol/1 and that of NET 10.1 (6.4-15.8) nmol/l. Thirty days after the last injection, the MPA level was 0.72 (0.46-1.1) nmol/l and that of NET 1.7 (1.2-2.3) nmol/l. The maximum level of exogenous E2 was 890 (700-1130) pmol/l after Cycloprovera and 1570 (870-2820) pmol/l after HRP-102 administration. Forty-nine and 41 days, respectively, after the last injection, a broad (endogenous) E2 peak was observed in all subjects, which was not followed by an ovulatory rise in PROG levels. The first ovulatory rise in PROG occurred between 71 and 90 days after the last Cycloprovera and 59 to 87 days after the last HRP-102 injection. One subject in each of the two groups failed to ovulate during the 90-day post injection period. Dating and morphometric analysis of the endometrial biopsy specimens obtained 20 to 24 days after the last injection revealed that the suppressive effect of Cycloprovera was stronger than that of HRP-102. Each injection of both formulations was followed by a bleeding-free period of approximately two weeks. The percentage of days with bleeding and spotting was 24% for Cycloprovera and 29% for HRP-102. It is concluded, that both monthly injectables inhibit follicle maturation for some 30 days and ovulation and corpus luteum formation for some 60 days, providing thus a considerable margin of safety in terms of the expected duration of contraceptive protection. PMID- 4028725 TI - The zoapatle. VII. Antiimplantation effect in the rat of zoapatle aqueous crude extract (ZACE) from Montanoa tomentosa and Montanoa frutescens. AB - Intrauterine administration of zoapatle aqueous crude extract (ZACE) from Montanoa frutescens on the fourth day of rat pregnancy, at concentrations equivalent to 50 mg and 5 mg of dry leaves, was associated with total inhibition of implantation sites. On the other hand, ZACE from Montanoa tomentosa equivalent to 50 and/or 100 mg of dry leaves, prepared and administered in the same fashion, did not inhibit the number of implants by day 11 of pregnancy. However, most implants were found abnormal, of blue color, poor orientation or spacing; these morphological changes could be considered as reabsorption sites. PMID- 4028726 TI - The zoapatle. VIII. Ultrastructural changes in endometrium of rats. AB - Intrauterine administration of Zoapatle aqueous crude extract (ZACE) prepared from Montanoa tomentosa s.s.p. tomentosa, on day 4 of pregnancy, did not alter the normal uterine morphological changes by days 5 and 8 of pregnancy in the rat. On the other hand, ZACE made from Montanoa frutescens caused profound alterations on the uterine structures, such as: focal loss of epithelial lining, thickened blood vessels and alterations in stroma cells in rat endometrium. Morphological alterations correlate well with the antiimplantation effect associated with the intrauterine administration of these plant extracts. Scanning electron micrographs of leaves from Montanoa tomentosa and Montanoa frutescens revealed striking differences in glandular secretion and trichomes. PMID- 4028727 TI - The zoapatle. IX. In vitro effect of Montanoa tomentosa and Montanoa frutescens upon human sperm and red cells. AB - The effect of zoapatle aqueous crude extract (ZACE) was further studied and partially characterized upon human and rabbit spermatozoa. ZACE prepared from Montanoa tomentosa s.s.p tomentosa did not influence sperm motility or viability in a wide range of ZACE concentrations tested; on the other hand, ZACE prepared from Montanoa frutescens had immediate and constant inhibitory effect upon motility and decreased cell viability. Red cell lysis was readily observed with ZACE-frutescens, but not with ZACE-tomentosa. The effect of time on ZACE frutescens potency for inducing red cell lysis was observed. PMID- 4028728 TI - Insertion technique, not design, affects expulsion rates of postpartum intrauterine devices. PMID- 4028729 TI - Long-term follow-up of pulmonary hypertension in patients with and without anorectic drug intake. AB - Over a period of up to 18 years, 24 patients (mean age: 33.8 years) with primary vascular pulmonary hypertension (PVPH) of unknown aetiology (group A) and 18 subjects (mean age: 45.3 years) with PVPH due to anorectic drug intake (group B) were comparatively studied. The following main tendencies became apparent: 1) The 10-year cumulative survival rate in group A (0.31) was lower than in group B (0.63). 2) Patients of group A showed more marked X-ray and ECG signs of pulmonary hypertension and right ventricular hypertrophy in comparison with group B. In contrast to group B, the ECG signs of hypertrophy in group A increased during the observation period. 3) Mean pulmonary artery pressure (PAP) significantly increased in group A (from 48.8 to 61.0 mmHg), while it decreased (from 47.6 to 33.3 mmHg) in group B. 4) The diameter of the descending branch of the right pulmonary artery increased with rising PAP only in group A, while the relationship between PAP and the Sokolow-Lyon index was significant only for the whole group of PVPH patients but not for the subgroups A and B. A regression of pulmonary hypertension in patients with anorectic drug intake was obvious, in contrast to the course in patients with PVPH of unknown aetiology. PMID- 4028730 TI - Influence of age on functional recovery after myocardial infarction. AB - Two age-groups of patients, of 45-59 and 65-69 years respectively, were investigated 10 days and 2 months after myocardial infarction. Left ventricular performance at rest was evaluated by radionuclide ventriculography, working capacity by submaximal heart rate-limited stress testing at discharge from the coronary care unit and maximal testing 2 months after the coronary attack. Resting ejection fraction remained unchanged while exercise tolerance increased in both age groups between the first and second examination but remained systematically lower in the elderly. The author conclude that although functional recovery after myocardial infarction is independent of age, physical capacity is lower in older patients during the acute phase as well as after early convalescence; resting ejection fraction remains, however, unchanged. PMID- 4028731 TI - [Unstable angina pectoris--diagnostic-strategic problems. A review]. PMID- 4028732 TI - Potential role of platelets in the pulmonary circulation. A review. PMID- 4028733 TI - Does pulmonary arterial hypertension influence the prognosis in patients with chronic obstructive lung disease? PMID- 4028734 TI - Contribution to the pathogenesis of essential hypertension: a multivariate analysis of associated factors. AB - This study attempts to develop a general aetiological concept of essential hypertension by multidimensional investigation of its various risk factors in childhood and adolescence. The investigation is based on married couples and their children (609 parents and their 639 children, a total of 1248 persons), all of them chosen under special aspects. Familial and environmental characteristics of children and young people with hypertension are compared with those of normotensive volunteers of the same age. The multi-dimensionally interacting factors found to be associated with hypertension in children are: hypertension, diabetes and early infarction in relatives of the first or second degree as well as overweight at birth, obesity, nutritional patterns in the earliest and later stages of life, social environment and physical activity of the children and adolescents. The familial factors most likely lead to a predisposition to hypertension while environmental factors may subsequently contribute to its manifestation. PMID- 4028735 TI - [Significance of noninvasive methods in cardiology]. PMID- 4028736 TI - Contrast Doppler echocardiography. AB - First clinical experiences with contrast Doppler echocardiography -- a new technique of cardiac ultrasound examination are described. The presence of contrast material within the right heart cavities following the peripheral vein injection is easily recognized by characteristic Doppler signal changes. This knowledge was used to detect a small amount of contrast passing through atrial (ASD) or ventricular septal defect (VSD) towards the left heart cavities despite the dominant left-to-right shunting. The high sensitivity of this technique in those conditions was attested to by correct diagnosis of 10 ASD and 3 VSD. Besides that, this technique is indicated also in selected cases of tricuspid regurgitation. The combination of both pulsed Doppler and contrast echo investigation seems to be advantageous in the diagnosis of the mentioned diseases. However, further study of this very specialized method is required. PMID- 4028737 TI - The effect of venostasis on several laboratory parameters in patients with predisposition to venous thromboembolism. AB - A series of laboratory tests was performed in 25 patients with recurrent venous thromboembolism as compared with 14 healthy person. The tests were combined with venostasis. The values of haematocrit, low-shear viscosity and fibrinogen were significantly higher in the preocclusion samples of the group with recurrent thromboembolism than in the controls. Venostasis did not increase the sensitivity of the tests. Platelet counts, euglobulin fibrinolysis, antithrombin III and total plasma proteins were not significantly increased either in preocclusion or in postocclusion samples as compared with the controls. PMID- 4028738 TI - CT scan lesion localization and response to melodic intonation therapy with nonfluent aphasia cases. AB - The purpose of this retrospective study was to investigate the relationship between CT scan lesion localization and good or poor response to Melodic Intonation Therapy (MIT) as measured by pre- and post-MIT treatment scores. The four good response (GR) cases improved in speech characteristics ratings for Phrase Length and Grammatical Form on the Boston Diagnostic Aphasia Examination; the four poor response (PR) cases showed no improvement. The GR cases had lesions which involved Broca's area and/or white matter deep to it plus large superior lesion extension into periventricular white matter deep to the lower motor cortex area for face. These GR cases had no large lesion in Wernicke's area and no lesion in the temporal isthmus or the right hemisphere. The PR cases, however, had bi-lateral lesions or lesion including Wernicke's area or the temporal isthmus. PMID- 4028739 TI - Mental rotation and visual laterality in normal and reading disabled children. AB - Normal and reading disabled children, aged from 11 to 13 years and matched for I.Q., were timed as they discriminated bs from ds. When the letters were presented only in their normal upright orientations, normal readers responded more quickly when they were presented in the right than in the left visual hemifield, while the disabled readers showed a slight but insignificant left hemifield advantage. When the letters were presented in varying angular orientations the reaction times indicated that both groups "mentally rotated" an internal representation of each letter to the upright in order to discriminate them. The two groups did not differ in the accuracy of discrimination or in the estimated rate of mental rotation, and there were no significant hemifield differences in this phase of the experiment. These data offer no support for the view that disabled readers are deficient in spatial ability, but confirm earlier evidence that they may suffer a lack of left-hemispheric specialization. PMID- 4028740 TI - The capacity of stroke patients to report dreams. AB - We studied the capacity of stroke patients to report dreams following awakening from REM sleep. Four left-hemisphere aphasia and two right-hemisphere visuospatial deficit patients reported dreams. The expression of ideas in dreams appeared normal despite the patients' waking difficulties. Given their similar rules of grammar, both dream and phonetic language modalities could emanate from common sites. PMID- 4028741 TI - Interhemispheric communication after section of the forebrain commissures. AB - Cognitive information is shown to be transmitted interhemispherically through channels other than the neocortical commissures, presumably through subcortical pathways. What crosses through these subcortical channels does not appear to include the name or identity of stimuli but rather is more contextual or associative in nature. Results obtained with a technique for prolonged visual lateralization indicate that this information, when used in conjunction with cognitive strategies, allows the cortically disconnected left hemisphere under certain conditions to verbally identify stimuli projected to the right hemisphere or to cross-compare bilateral input. The presence of this subcortical communication would thus appear to help explain some of the increasing exceptions to characteristic disconnection symptoms reported among split-brain subjects. In particular, the present results challenge reports which have attributed oral naming of stimuli in the left visual hemifield to the typical disconnected right hemisphere. PMID- 4028742 TI - Object reversals after parietal lobe infarction--a case report. AB - A case is described of a mixed manually dominant man with a right parietal infarction who demonstrated reversals in object manipulation. Although mirror reversals in parietal lobe dysfunction and right-left spatial reversal in conjunction with mirror writing have been reported previously, object and spatial reversal to this extent has not been reported. The theoretical implications of the absence of mirror writing here, in relation to side of brain lesion and handedness, are discussed. PMID- 4028744 TI - Asymmetrical facial expressions: a different interpretation. PMID- 4028743 TI - On comprehension across the adult lifespan. AB - To test whether healthy elderly subjects develop language comprehension strategies to compensate for decreases in pure-tone audition, we tested 128 healthy subjects aged 30-79 on two tasks: (1) Comprehension materials from the Boston Diagnostic Aphasia Examination (Goodglass and Kaplan, 1972) presented over babble noise with and without the speaker's face visible; and (2) the Kalikow et al. (1977) Speech Perception in Noise test, which assesses the effect of semantic predictability on sentence-final word intelligibility. Whereas, as predicted, overall performance decreased with advancing age, it appeared, unexpectedly, that older and younger adults were equally affected by the absence of visual input and the absence of semantic predictability. PMID- 4028745 TI - Asymmetrical facial expressions indeed: a reply to Dane and Thompson. PMID- 4028746 TI - Unilateral visual agnosia. AB - A case of unilateral visual agnosia for all types of stimuli limited to the left visual hemifield and associated with a right occipital temporal vascular lesion is reported. Questions raised by this case of hemiagnosia as compared to previous ones are discussed. PMID- 4028747 TI - Responses of opsonic substances to major trauma and sepsis. AB - Adequate opsonic capability is vital for normal host defense against infection. The presence of complement fraction 3 (C3) indicates both classical and alternative pathways of complement activation, while complement fraction 4 (C4) indicates only classical pathway activation. C-reactive protein (CRP) functions as an opsonic substance. We measured serum levels of C3, C4, and CRP in 32 trauma patients. Six suffered minor injuries and 26 suffered major injuries. Nineteen of the major-injury patients developed post-trauma sepsis. Complement levels fell immediately after injury and remained low for approximately 8 days in all patients. CRP levels rose by 12 h, peaked at 48 h, and correlated with the severity of injury and the presence of sepsis. Elevated CRP levels after 4 days postinjury indicated the presence of sepsis in all cases. CRP elevations preceded clinical diagnosis by an average of 2.4 days. Serial measurements of CRP are valuable in monitoring the course of trauma patients and may indicate the presence of septic complications before clinical detection. PMID- 4028748 TI - Prevention of the adult respiratory distress syndrome with dipyridamole. AB - Because the formation of platelet thrombi has been incriminated in the development of the adult respiratory distress syndrome (ARDS), we tested the hypothesis that early administration of antiplatelet agents might protect the lungs in patients at risk to develop ARDS after circulatory shock. This double blinded study included 40 patients treated with either 3 mg/kg . 24 h of dipyridamole or a corresponding dose of placebo after an episode of hemorrhagic, traumatic, or septic shock. Each patient also received 100 mg of aspirin daily. Arterial blood gases and chest x-rays were not significantly different between dipyridamole and placebo groups. Moreover, two patients receiving dipyridamole but none receiving placebo developed ARDS. This pilot study does not support a beneficial effect of dipyridamole in the prevention of ARDS after circulatory shock. PMID- 4028749 TI - Diagnosis and therapy of necrotizing tracheobronchitis in ventilated neonates. AB - From January 1983 to September 1984 our neonatal ICU (NICU) treated eight endotracheally intubated infants who had suspected airway obstruction characterized by hypercarbia dissonant with severity of lung disease and difficulty in ventilation with lack of chest movement, both on conventional intermittent mandatory ventilation and high-frequency oscillation. Bronchoscopic removal of necrotic tissue was possible in six infants, two of whom survived. Bronchoscopy showed desquamation of epithelial surfaces, leaving encrusted exudations considered to be characteristic of necrotizing tracheobronchitis (NTB). The four nonsurvivors of bronchoscopy and one of the infants not submitted to bronchoscopy had NTB confirmed at autopsy. NTB was not associated with any specific lung disease, humidifier, or ventilator. The autopsy frequency of NTB during this period was 5 per 160 NICU admissions. A separate chart review of unselected autopsied cases in 1981 and 1982 showed that 12 of 284 neonates admitted to the NICU had NTB. NTB appears to be a rediscovered condition related to endotracheal intubation and mechanical ventilation using high mean airway pressures. PMID- 4028750 TI - Effects of changes in abdominal pressure on left ventricular performance and regional blood flow. AB - Many clinical conditions are associated with an increase in abdominal pressure. While the effects on venous return have been studied in the past, little attention has been given to the effect of abdominal pressure on left-sided hemodynamic events. The effects of acute changes in abdominal pressure (Pab) on left ventricular (LV) hemodynamics and outflow distribution were evaluated in ten open-chest dogs, which had undergone right heart bypass to eliminate the influence of changes in Pab on systemic venous return. Pressures were measured in the left atrium (Pla), aorta (Pao), and stomach (Pab). Electromagnetic flow probes were positioned around the ascending aorta (Qaa), descending aorta (Qda) and the innominate or subclavian artery (Qin) to reflect total cardiac output and the respective regional caudad and cephalad blood flows. Compressing the abdomen to increase acutely Pab (9.2 +/- 0.6 torr) also significantly increased Pao (7.8 +/- 1.2 torr), Pla (1.7 +/- 0.4 torr), and Qin (15.2 +/- 4.5%), while Qaa (-9.5 +/- 2.0%) and Qda (-26.3 +/- 7.0%) significantly decreased. Opposite findings were obtained immediately after release of abdominal compression. Thus, an acute increase in Pab with a constant pulmonary artery inflow increased the afterload imposed on the left ventricle and redistributed LV output, with a reduction in flow to the abdomen. Part of the fall in Qaa and increase in Pla could be attributed to passive elevation of the diaphragm by the increase in Pab, i.e., heart-lung-diaphragm interdependence.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4028751 TI - Cardiopulmonary effects of hypertonic saline in canine oleic acid-induced pulmonary edema. AB - Vasoactive drugs may increase intrapulmonary shunt in patients with permeability edema. Because 7.5% hypertonic saline solution has cardiotonic properties, we studied its hemodynamic and pulmonary effects in a canine model of oleic acid induced lung injury. Immediately after saline infusion, there were increases in cardiac output (2.0 +/- 0.1 to 3.4 +/- 0.2 L/min; p less than .001) and intrapulmonary shunt (50.3 +/- 4.4 to 57.3 +/- 3.2%; p less than .01) without alteration in arterial or mixed venous oxygen tension. Although arterial oxygen content decreased from 16.4 +/- 1.1 to 14.4 +/- 0.9 ml/dl (p less than .001), paralleling the change in hemoglobin concentration, oxygen delivery to the tissues increased from 327 +/- 23 to 486 +/- 36 ml/min (p less than .001). These effects were transient, inasmuch as all values returned to preinfusion levels within 30 min. Tissue oxygen consumption increased proportionately with cardiac output, and the directional change in arterial oxygenation was similar to the change in mixed venous oxygen tension. We conclude that tissue oxygen delivery improves after hypertonic saline infusion despite changes in intrapulmonary shunt and oxygen consumption. However, any benefit appears to be transient. PMID- 4028752 TI - Early extubation after surgical repair of congenital heart disease. AB - Of 220 pediatric patients recovering from surgical repair of congenital heart disease, 147 (67%) met our criteria for early extubation and were extubated either in the operating room or within 6 h after admission to the surgical ICU. The duration of postoperative mechanical ventilation correlated with the duration of cardiopulmonary bypass during surgical repair. In patients undergoing repair of ventricular septal defect, preoperative measures of pulmonary vascular status (PPA/PAO and RP/RS) also correlated with the duration of mechanical ventilation. PMID- 4028753 TI - Etiologic diagnosis of bacterial nosocomial pneumonia in seriously ill patients. AB - We identified retrospectively 19 critically ill, intubated patients in whom tracheobronchial secretions had been cultured before antimicrobials were administered. Each of these patients had bacterial nosocomial pneumonia, as diagnosed by a positive bacterial culture from blood, pleural fluid, percutaneously aspirated lung material, special endobronchial brushings, and/or postmortem lung specimens. In 11 (58%) patients, the predominant organism in the tracheobronchial secretions was the same one identified in the diagnostic culture. However, in eight (42%) patients, the infecting bacteria were either not predominant or did not grow in the culture of respiratory secretions. We conclude that standard microbiologic studies of central tracheobronchial secretions are not always reliable for establishing the etiology of a bacterial nosocomial pneumonia in this type of patient. PMID- 4028754 TI - Infectious complications and duration of intracranial pressure monitoring. AB - We studied 65 children with acute brain injury to determine how the risk of infectious complications changed with duration of intracranial pressure (ICP) monitoring. More than half of the 72 monitors inserted in these patients were in place at least 7 days (range 1 to 28). Nine infections occurred on days 2 through 11. The overall risk was 1.5 infections per 100 monitor-days. After day 6 the risk of subsequent infection diminished, as did the percent of monitors which subsequently became infected. The declining risk of infection over time suggests that infection is introduced at the time of monitor insertion. These findings justify a protocol in which a single ICP monitoring device is used as long as necessary, with reinsertion of a new monitor only if a malfunction occurs, or if daily surveillance cultures demonstrate an infection. Routine reinsertion of a new monitor might increase risk by unnecessarily re-exposing the patient to contamination at the time of insertion. PMID- 4028755 TI - Bicarbonate hemodialysis of patients with acute renal failure and severe sepsis. AB - During hemodialysis (HD), septic patients with acute renal failure (ARF) often exhibit severe hemodynamic instability, with a fall in BP that requires a large volume infusion or even cessation of dialysis. To investigate the hypothesis that acetate transfer plays a role in the BP decrease, we compared acetate (Ac) and bicarbonate (Bi) HD in ten septic ARF patients. Patients were dialyzed daily for 4 h with a single-pass system and 1.1 m2 cuprophan dialyzers, alternately using Ac and Bi as the dialysate buffer. Heart rate and systemic arterial resistance did not change significantly during use of either buffer, and changes in pulmonary wedge pressure were similar. However, decreases in cardiac output and mean arterial pressure were more pronounced during Ac-HD than during Bi-HD. Rapid correction of metabolic acidosis and a larger decrease of plasma potassium concentration occurred during Bi-HD. These results suggest that Bi-HD was better tolerated than Ac-HD because of changes in myocardial contractility that may be related to different effects on acid-base status and plasma potassium concentrations. PMID- 4028756 TI - Influence of hypothermia on the pharmacokinetics of gentamicin and theophylline in piglets. AB - The influence of hypothermia on gentamicin and theophylline pharmacokinetics was studied in anesthetized pigs given an iv bolus of gentamicin and theophylline during normothermia (37 degrees C) and again 1 wk later after the induction of controlled hypothermia (29 degrees C). During hypothermia, the elimination half time for gentamicin was significantly prolonged (135 +/- 19 min at 37 degrees C vs. 187 +/- 7 min at 29 degrees C), and there were significant decreases in the volume of the central compartment (Vc) of gentamicin, the gentamicin volume of distribution (Vd), and the gentamicin total body clearance (TBC). Hypothermia was associated with a small but significant decrease in theophylline Vd and Vc, but no change in TBC. In separate experiments, cardiac output decreased during the induction of hypothermia in a temperature-dependent fashion. The changes in gentamicin Vd and TBC may be explained by the decrease in cardiac output and the associated decrease in glomerular filtration rate. This study suggests that the elimination of theophylline, which has a relatively low hepatic extraction ratio, is not influenced by the hypothermia-induced decrease in liver blood flow. PMID- 4028757 TI - Real-time analysis of the change in arterial oxygen tension during endotracheal suction with a fiberoptic bronchoscope. AB - An intra-arterial Clark-type polarographic oxygen electrode was used with a fiberoptic bronchoscope for real-time analysis of the PO2 change during 1 min of suction in patients spontaneously breathing oxygen. There was a strong correlation between values obtained from the intra-arterial electrode (PiO2) and those from blood samples (PaO2), before and at the end of suction; the PiO2/PaO2 ratio was close to one. Continuous PiO2 recordings during suction without supplemental oxygen showed little change in the early period of suction, followed by a steep drop continuing even after suction. This drop in PiO2 was partially attenuated by providing oxygen with high-frequency jet ventilation and was almost completely attenuated by the use of a suction adaptor. Changes in the inspired oxygen concentration indicated the importance of keeping this variable constant during suction to prevent hypoxemia. PMID- 4028759 TI - SCCM's new horizons conference on sepsis and septic shock. PMID- 4028758 TI - Continuous polarographic monitoring of intra-arterial oxygen in the perioperative period. AB - Intra-arterial PO2 (PiO2) was polarographically monitored in ten critically ill patients during induction of anesthesia, the intraoperative period, extubation, and the immediate postoperative period; 147 PiO2 values were then paired with simultaneous measurements of PaO2. Mean PiO2 closely followed mean PaO2 over a wide range of values (r = .97), and the continuous, online real-time PiO2 readings provided a useful early warning system for hypoxemia during crisis periods. Technical problems included catheter clotting from improper flushing, changes in PiO2 due to changes in body temperature, the need for in vitro and in vivo calibration, and sensor drift. However, these problems were resolved by appropriate catheter management and sensor calibration. PMID- 4028760 TI - Stroke as a complication of carotid sinus massage. AB - A 77-yr-old white man recovering from aortobiiliac bypass surgery suffered a sudden stroke within 30 min after carotid sinus massage was performed in an attempt to treat supraventricular tachycardia. Even though carotid digital subtraction angiography and angiograms were negative for carotid artery disease, we believe that there was enough plaque or vascular disease to precipitate the stroke. Considering the prevalence of atherosclerotic vascular disease in the general population, we recommend avoiding carotid sinus massage in elderly patients, even in the apparent absence of carotid artery disease. PMID- 4028761 TI - Occult metoprolol overdose. AB - A patient with an apparent dilantin and phenobarbital overdose displayed hypotension and oliguria resistant to usual cardiotonic drugs and volume loading. In addition, she required an unusually high dose of epinephrine for resuscitation. Metoprolol, a beta-blocker not included on the drug screen, was subsequently implicated. An overdose of this drug should be suspected in patients whose hypotension is resistant to usually effective doses of inotropic and chronotropic agents. PMID- 4028762 TI - Acute ethylene glycol poisoning. PMID- 4028763 TI - Accidental extubations in pediatric patients. PMID- 4028764 TI - Intravenous salbutamol for status asthmaticus. PMID- 4028765 TI - Simplified method for mu/kg.min intravenous infusion. PMID- 4028766 TI - Treatment of hypochloremic metabolic alkalosis by rectal infusion of calcium chloride. PMID- 4028767 TI - Frequency of wedge pressure errors in the ICU. AB - Using 94 flow-directed pulmonary artery catheters in 53 ICU patients, we obtained prospectively 282 pulmonary artery wedge pressure (WP) measurements from 286 attempts. After catheter manipulation, 96% of these WP measurements were ultimately free of technical problems, and 84% were confirmed by aspiration of pulmonary capillary blood from the wedge position. The 95% confidence interval for repeated measurements of WP in stable ICU patients was 4 mm Hg. The WP measurement error was defined as the difference between unconfirmed and confirmed WP pairs obtained from stable patients. The probability of encountering a WP measurement error of at least 4 mm Hg was 33% for the 93 WP measurements with technical problems, 5% for the 189 WP measurements without technical problems, and 14% for the entire set of 286 WP measurement attempts. Quality control procedures, including dynamic response testing, easily identified most errors. PMID- 4028768 TI - Cerebrospinal fluid myelin basic protein as a prognostic marker in patients with head injury. AB - Despite increasing interest in identifying biochemical and serologic markers to judge the severity of closed head injury in comatose patients, clinical variables remain the most readily available methods for assessing prognosis. In a series of 35 severely head-injured comatose patients, the cerebrospinal fluid (CSF) level of myelin basic protein (MBP) was analyzed by radioimmunoassay. MBP levels during the first week after injury were significantly correlated with the Glasgow outcome score at 7 days (p less than .005), 3 months (p less than .005), and 6 months (p less than .05) postinjury. Measurement of CSF MBP appears to be a useful laboratory adjunct to clinical assessment, for judging the outcome of severely head-injured patients. PMID- 4028769 TI - Comparison of internal and external jugular cannulation of the central circulation in the pediatric patient. AB - Percutaneous catheterization of the central circulation via the internal jugular vein was compared to cannulation via the external jugular vein, in a retrospective review of 200 pediatric patients. The internal approach resulted in an 86% rate of successful cannulations with 99.9% of the catheters positioned in the thorax; this technique was accompanied by an 8% incidence of carotid artery puncture. The external jugular route eliminated the risk of carotid artery puncture; however, it was successful in only 65% of the attempts, and 14% of the successful cannulations had catheter tips incorrectly positioned outside the thorax. PMID- 4028770 TI - Intravenous amiodarone in the treatment of refractory arrhythmias. AB - Oral amiodarone's slow absorption handicaps rapid treatment of life-threatening arrhythmias. We used iv amiodarone to treat ten patients with hemodynamically significant atrial arrhythmias and life-threatening ventricular arrhythmias refractory to all conventional medical treatment. Arrhythmias were controlled in nine patients, five of whom became long-term survivors on oral amiodarone. Two patients died of cardiovascular collapse within 24 h of initiation of iv amiodarone. One other patient died postoperatively of cardiovascular collapse while on oral amiodarone, 2 wk after iv amiodarone. Another patient died of an unrelated cause 13 months after initiation of amiodarone. These results suggest that iv amiodarone is effective in controlling refractory atrial and ventricular arrhythmias and may shorten the latency period. PMID- 4028771 TI - Colonization of intravascular monitoring devices. AB - This randomized prospective study of all invasive catheters inserted in our ICU tested the hypothesis that daily dressing changes would reduce the 25% infection rate associated with these catheters. Significant growth was noted in eight (7%) of 133 vs. nine (6.7%) of 135 skin cultures from patients whose dressings and infusion tubings were changed at 24 vs. 72 h, respectively. Catheter tip cultures were positive in six (5.9%) of 102 vs. eight (7.5%) of 107 for the 24- and 72-h groups, respectively. Paradoxically, blood cultures were positive in three (6.7%) of 45 vs. 12 (23.1%) of 52 from the 24- and 72-h groups, respectively (p less than .03). However, there was no correlation between the positive blood cultures and the organisms cultured from the catheter tips. PMID- 4028772 TI - Effect of body inversion on hemodynamics determined by two-dimensional echocardiography. AB - The purpose of this study was to determine if head-down inversion of normal men from a supine position would increase blood return to the heart. Eight healthy, normovolemic men were placed into 10 degrees, 30 degrees, 60 degrees, and 90 degrees head-down tilt positions. BP and two-dimensional echocardiograms were recorded at the supine baseline and immediately after inversion. There was no significant change in left ventricular end-diastolic volume, stroke volume, cardiac output, or BP with inversion, except for a significant increase in diastolic pressure at the 60 degree position. The efficacy of placing hypotensive shock patients in the head-down tilt position is discussed. PMID- 4028773 TI - Evaluation of a computer-based clinical reference library in an ICU. AB - A computer-based clinical reference library (CRL) was developed as a subsystem of the Hewlett-Packard 5600 A patient data management system for use in the 10-bed ICU at the University of Alberta Hospital. The CRL contains 20 information modules and can be accessed at both bedside and central consoles. Information is classified under headings of: definition, incidence, etiology, pathophysiology, pathology, bacteriology, clinical course, diagnosis, treatment, complications, prognosis, and references. The CRL was evaluated by a nonrandomized pretest/post test, control-experimental research paradigm. Medical students and residents exposed to the system "acquired" significantly more knowledge than their counterparts in a control group. Medical students and nurses used the system for continuing medical education, whereas residents accessed the system for problem solving. Nurses had strong negative views about the computerized patient data management system and tended not to use the CRL. Correlation between instruction time and gain scores was positive but test correlation coefficients for each subgroup were not significantly different. PMID- 4028774 TI - Intensive care nurse: job tension and satisfaction as a function of experience level. AB - It has been suggested that experienced ICU nurses are better able to cope with the complexity of their environment and, as a result, achieve greater satisfaction than their less-experienced counterparts. One hundred ten ICU nurses from a large Midwestern medical center were requested to fill out a job tension and job satisfaction questionnaire. The results showed that job tension and job satisfaction remained relatively constant as the number of years on the job increased, refuting the notion that work experience automatically facilitates a mastery of environmental demands. As expected, job tension was inversely related to job satisfaction. PMID- 4028775 TI - Pseudodysrhythmia during dialysis. PMID- 4028776 TI - Hyperbaric oxygen therapy for Fournier's gangrene. AB - Soft-tissue infections with tissue necrosis, due to mixed aerobic and anaerobic organisms, are an accepted indication for hyperbaric oxygen (HBO) therapy. A unique type of such infection is Fournier's gangrene. This condition represents a serious risk to life and patients should be treated rapidly and aggressively. We treated three such cases by HBO. All three patients recovered from the infection, although one died later from renal and pulmonary complications. PMID- 4028777 TI - Another chance for therapeutic hypothermia? PMID- 4028778 TI - Use of isoproterenol in infants. PMID- 4028779 TI - A simple computer program for obtaining gas exchange indices. PMID- 4028780 TI - Effect of cryoprotectants on the viability and function of unfrozen human polymorphonuclear cells. AB - High concentrations of membrane permeable cryoprotectants are necessary to protect human polymorphonuclear leukocytes from osmotic stress injury during freezing, but there are reports that some cryoprotectants are chemically toxic. Cells were exposed to various concentrations of glycerol, dimethyl sulfoxide, or ethylene glycol for 5 min to 2 hr at 37, 22 or 0 degree C, adding or removing the cryoprotectant either slowly or rapidly. Assays included cell number recovery, membrane integrity, phagocytosis, microbicidal ability, and chemotaxis. We conclude that (1) 1 and 2 M concentrations generally are not toxic if they are added and removed slowly at 22 degrees C; (2) addition and removal of glycerol at 0 degree C was injurious even at 1 M; (3) slow addition and removal allowed better recovery than rapid addition or removal; (4) salt concentration in cryoprotectant solutions should be adjusted to isotonic on the basis of moles per liter of solution, rather than moles per kilogram of water; (5) the toxicity reported by other investigators can be largely explained by osmotic stress or dilution shock rather than chemical toxicity; and (6) ethylene glycol is the easiest cryoprotectant to add to and remove from these cells. PMID- 4028781 TI - The effects of dimethyl sulfoxide on the osmotic properties of a rat megakaryocytopoietic cell line. AB - Dimethyl sulfoxide (DMSO) at 0.6 M alters the osmotic state of intracellular water in a line of rat megakaryocytopoietic cells. The response is a function of temperature. Maximal structuring of water occurs at 24.7 degrees C, while disorganization occurs at 30 and 37 degrees C. Little effect occurs at 3 and at 18 degrees C. Parallel measurements of membrane permeability to water indicate that DMSO inhibits the osmotic exit of water at all temperatures. Maximal inhibition occurs at 24.7 degrees C, the same temperature at which maximal organization of water occurs. These findings emphasize the possible role which water may play in explaining the diverse functions of DMSO as cryogenic substance, promoter of cell fusion, and stimulator of cell differentiation. PMID- 4028782 TI - Membrane stabilization during freezing: the role of two natural cryoprotectants, trehalose and proline. AB - The relative effectiveness of two natural cryoprotectants, proline and trehalose, in preserving membrane structure and function during freezing was studied. Isolated vesicles of sarcoplasmic reticulum (SR) from lobster muscle (Homarus americanus) were employed to study changes in structure and function during rapid freeze-thaw conditions. Both proline and trehalose were shown to effectively preserve the structure (assessed with freeze fracture) and function (assessed by the ability of the membranes to transport calcium) in the frozen vesicles. As a first step toward determining the mechanism of cryoprotection by these compounds, we have investigated their effectiveness in inhibiting freezing induced fusion between phospholipid vesicles. Pamiltoyloleoyl-phosphatidylcholine: phosphatidylserine (85:15 mole ratio) small unilamellar vesicles (SUVs) were made incorporating one of the following fluorescent probes, and energy donor, cholesteryl anthracene-9-carboxylate, or an energy acceptor, nitrobenzo-2-oxa-1,3 diazole phosphatidylethanolamine to investigate the amount of membrane mixing during rapid freeze-thaw cycles, and storage at -20 degrees C. Membrane mixing was measured as an energy transfer from donor to acceptor when donor vesicles and acceptor vesicles were mixed before a particular freezing treatment. Membrane mixing was correlated with structural changes in these membranes by freeze fracture analysis. Both trehalose and proline were found to be more effective in preventing membrane mixing between SUVs than the standard protectants, glycerol and dimethylsulfoxide. PMID- 4028783 TI - Glucocorticoids and hypothermic induction and survival in the rat. AB - Glucocorticoids (GC) are important for thermoregulatory responses to low environmental temperatures. Pretreatment of hamsters, which are capable of natural hibernation, with cortisone acetate has been demonstrated to improve carbohydrate homeostasis during hypothermia. The objectives of the current studies were to evaluate the effects of GC pretreatment of a nonhibernator, the rat, on (i) cooling time, (ii) carbohydrate homeostasis (in terms of liver and cardiac glycogen concentrations and plasma glucose concentration), and (iii) duration of survival in hypothermia. In addition, the effects of liver glycogen depletion on cooling times and survival were examined. Hypothermia was induced in rats by exposure to a helium:oxygen (80:20, Helox) atmosphere at 0 degree C. Pretreatment of rats with triamcinolone acetonide (1.5 mg/kg/day, sc, 48, 24, and 1 hr prior to induction) significantly (P less than 0.05) lengthened induction time, while fasting was associated with a significant decrement (25%). While liver and cardiac glycogen levels in control and GC-treated rats fell approximately 45% during cooling, this reduction occurred over a significantly greater period of time in treated rats and suggests a sparing of glycogen or increased capacity for its production in response to GC. Glycogen utilization was accompanied by a hyperglycemia in control, GC-treated, and fasted groups. Survival in hypothermia at a rectal temperature of 14-15 degrees C in GC-treated (9.5 +/- 1.2 hr) and fasted (10.9 +/- 0.9 hr) rats was not significantly different from control (10.5 +/- 1.1 hr) values. These findings suggest that treatment with GC can increase the thermogenic capacity of the rat (as evidenced by an increased induction time) and promote carbohydrate homeostasis, but does not contribute to an enhancement of survival in the hypothermic nonhibernator. PMID- 4028784 TI - "Hidden" popular illnesses in primary care: residents' recognition and clinical implications. AB - This study documents that ethnomedical beliefs and practices play an important role in primary care in a southern community. Thirty-three of 73 patients from a rural Appalachian area coming to a university primary care internal medicine practice presented 54 ethnomedical complaints such as "high blood" (24.1%), "Weak 'n dizzy" (22.2%), "nerves" (16.7%), "sugar" (5.6%) and "fallin' out" (3.7%). Thirty-three patients had both biomedical and ethnomedical complaints, 40 patients had biomedical complaints without ethnomedical complaints and no patients presented with ethnomedical complaints alone. Over two-thirds of all patients consulted non-medical personnel for their complaints, mostly family and friends, and 70 percent self-treated prior to clinic consultation. Patients presenting with ethnomedical complaints when compared with those presenting with biomedical complaints sought advice of non-physicians significantly more often (p less than 0.02); no statistical difference, however, was found in their self treatment practices. Ninety-two of 130 biomedical complaints were recorded by the patient's physician but none of the 54 ethnomedical complaints were formally recorded (p less than 0.001). The high incidence of ethnomedical complaints in this population and the failure of physicians to recognize these complaints demand that primary care medicine residents be taught improved history-taking skills and the essentials of ethnomedical illnesses if they are to provide culturally-sensitive patient care. PMID- 4028785 TI - Chronic disease: the sick role and informed consent. PMID- 4028786 TI - Psychosomatic symptoms, stress, and modernization: a model. AB - The quantity of research on the effects of stress on disease has increased substantially in recent years, but little effort has been devoted to examining the effects of cultural influences in the stress process. A model is proposed in this paper in which cultural context exerts a modifying influence on the relationship between sociocultural stressors and psychosomatic symptoms, specifically in the context of modernization. In change situations involving increasing modernization there is increased differentiation in systems of social stratification within a community, due to increased potential for upward social mobility. The individuals who are upwardly mobile adopt a particular style of life, involving the acquisition of western consumer goods, as symbolic of their success. Lower class individuals strive to attain this same style of life as a claim to a higher status social identity, but their lower economic condition results in stressful incongruities and higher psychosomatic symptoms. Individuals who are successful in upward mobility are confronted by a different set of stressors that are primarily intrapsychic in nature. Events and circumstances perceived as threats to their self-identity are related to more psychosomatic symptoms. Thus, the meaning of specific stressors changes depending on the sociocultural context of the individual, and this meaning serves as a bridge between environmental circumstances and physiological outcomes. This model receives substantial empirical support in two field studies. Limitations of the model and implications for future research are discussed. PMID- 4028787 TI - A cross-cultural study of depressive symptomology. AB - Black (N = 26), white (N = 26) and Overseas Chinese (N = 32) college students were surveyed with Zung's Self-rating Depression Scale (SDS). With the exception of two items where marginally significant differences were found, there were no quantitative differences in the results across these ethnic groups. Inter-item analyses, factor analyses and comparison of factor profiles indicated that the items clustered in different configurations for the three groups. The factors contributing the most variances differed in their item contents across the ethnic groups: a mixture of affective and somatic complaints characterizes the black group; existential and cognitive concerns characterize the white group and somatic complaints characterize the Overseas Chinese group. Discussion was focused on issues concerning cultural conception of psychological difficulties, communication styles used to communicate these difficulties and situational variables affecting performances on psychological diagnostic tests. PMID- 4028788 TI - Ultrastructural cytochemistry: effect of Sorbinil on arylsulfatases in cataractous lenses. AB - We have demonstrated an increase in activity of arylsulfatase A and B during galactose induced cataract development in rats. Our recent investigation shows that acid phosphatase activity, which increases substantially during galactose cataract development in rats, could be contained to near normal level if Sorbinil, an aldose reductase inhibitor, was fed along with galactose to the rat. We have observed that the activity of other lysosomal enzymes, arylsulfatase A and/or B, also increases during galactose cataractogenesis. In the present report, we provide information with regards to the effect of Sorbinil on the activity of these enzymes during cataractogenesis. A modified Hopsu-Havu and Helminen method (1974) with p-nitrocatecholsulfate as substrate was used for localization of both arylsulfatase A and B; and the method of Hara et al. (1979) was utilized to obtain quantitative data on the level of arylsulfatase A and B activity. Ultrastructural cytochemistry shows that arylsulfatase activity in all lenses was primarily localized in epithelial cells in lysosomes with very little or no activity in cortical fibers. The number of arylsulfatase positive lysosomes and the activity level of these enzymes increased with the progression of cataract development. Galactose induced damage to lens morphology and increase in activity of arylsulfatase A and B was inhibited by inclusion of 50mg/Kg (diet) Sorbinil in the galactose containing cataractogenic diet. However, Sorbinil had no significant effect on the enzyme activity following the establishment of mature cataracts. PMID- 4028789 TI - Blood flow in aphakic rabbit eyes after sub-chronic glaucoma drug treatment. AB - Ocular blood flow was measured in aphakic rabbit eyes using a radioactive microsphere technique following sub-chronic three times a day treatment with one of the following drugs: ecothiophate iodide (0.125%), pilocarpine (4%), epinephrine (2%), norepinephrine (2%) or timolol (0.5%). The results show that regional ocular blood flow was statistically normal after this treatment regimen compared to both normal and aphakic control eyes. Ecothiophate did statistically increase choroidal blood flow and, although not statistically significant, other drugs did induce trends which may be relevant to drug use. PMID- 4028790 TI - Changes in the normal corneal endothelial cellular pattern as a function of age. AB - Human endothelial morphologic changes were quantitated by specular microscopy and computer-assisted morphometry to establish normal baselines of various morphologic parameters. Cellular polymegethism and cellular pleomorphism increases with age, and normal baseline parameters are detailed. Furthermore, no significant difference in any morphologic parameters between the right and left eye and between central and peripheral endothelium was detected in the normal corneas examined. These normal morphologic baselines can possibly be utilized to detect early corneal endothelial pathology and/or cell loss nondetectable by cell density measurement. PMID- 4028791 TI - Spatial distribution of oxygen in the cornea of a closed eye wearing a gas permeable contact lens. PMID- 4028792 TI - A noninvasive optical method to measure oxygen tension at the corneal epithelium. AB - Corneal redox fluorometry is presented as an alternative method to noninvasively measure the oxygen tension in equilibrium with the tear film. The application of this method to the study of the effects of a contact lens on the tear film oxygen tension is described. The development of a clinical corneal redox fluorometer would permit noninvasive measurements of the effects of contact lens induced corneal hypoxia on corneal physiology. These studies could investigate the effects of corneal hypoxia at the cellular level and result in a new level of understanding of the processes involved. PMID- 4028793 TI - Method for quantitative evaluation of corneal shape changes by contact lens molding. PMID- 4028794 TI - The influence of calcium in the tear-side perfusate on desquamation from the rabbit corneal epithelium. PMID- 4028795 TI - Change in metabolite concentration of tears after short-term wearing of contact lenses in nonadapted eyes. PMID- 4028796 TI - Perfluoro-1-methyldecalin as a potential oxygen carrier with fluid scleral lenses. PMID- 4028797 TI - Threshold and signal detection measurements of the effect of soft contact lenses on corneal sensitivity. PMID- 4028798 TI - Purification and properties of human cataractous lens glyceraldehyde-3-phosphate dehydrogenase. AB - Glyceraldehyde-3-phosphate dehydrogenase has been shown to occur in three different forms in the human adult cataractous lens: a membrane bound form (M) and at least two cytosolic isozymes: I1 and I2. Similar Km's for substrate, cofactor and HAsO4 were established for each form and all three forms, to differing degree, require a reduced sulfhydryl group for maximum activity. A variety of phosphonucleosides (ATP, ADP, AMP and 3' 5' cyclic AMP) as well as NADH inhibit enzyme activity. Inhibition by ATP is non-competitive whereas cyclic AMP and NADH compete for the cofactor binding site. Chloride ion stimulates and inhibits enzyme activity at low and high concentrations respectively. PMID- 4028799 TI - 86-Rb efflux in normal and cataractous human lenses. AB - 86Rb efflux has been studied in normal lenses and in human senile cataracts. The rate constant (Ki) of the efflux gradually increases in cataractous lenses with progression of lens damage. Efflux experiments run in the presence of BaC12 suggest that a progressive activation of BaC12 inhibitable efflux routes occurs in cataractous lenses. In the final stages of opacification the ineffectiveness of BaC12 enriched or Ca++ free media on the efflux suggests that a direct disruption of the lens membranes has occurred. PMID- 4028800 TI - Corneal endothelial changes in diabetic dogs. AB - The corneal endothelium of alloxan diabetic dogs was examined by wide-field specular microscopy and compared to that of age-matched non-diabetic dogs. Computer-assisted morphometry of individual cells showed that the diabetic dog endothelium had marked polymegethism and pleomorphism similar to that previously described in diabetic patients. There also appeared to be a positive correlation between the degree of these endothelial changes and the diabetic control as demonstrated by HbA1 concentration. PMID- 4028801 TI - Tapetal degeneration in cats with Chediak-Higashi syndrome. AB - The Chediak-Higashi syndrome (CHS) is a genetic disorder of man, cats, and four other animal species. Enlarged cytoplasmic granules, including lysosomes and melanosomes, characterize the syndrome. Cats affected with CHS lack funduscopically visible tapeta. In normal cats, the tapetum is the light reflecting cellular layer located in the choroid. The tapetal cells contain bundles of parallel cytoplasmic rods. In this study, eyes from CHS and control cats were examined by light microscopy and transmission electron microscopy. The CHS kittens up to 14 days of age had tapeta which appeared similar to those of the controls. By 28 days of age some of the CHS tapetal rods had degenerated. Degeneration of the tapetal rods progressed rapidly and by 56 days of age there was a dramatic difference in the ultrastructural appearance of the tapetal cells. All the rods had degenerated and the contents of the tapetal cells were disorganized. The tapetal layer gradually thinned over a period of several months until the layer was absent or nearly so in CHS cats over one year of age. This study demonstrated that there is a previously overlooked degenerative component of the Chediak-Higashi syndrome. PMID- 4028802 TI - Pretreatment with detergents modulates the effects of epinephrine on uveal flow and intraocular pressure. AB - Prior administration of detergents modulates the effects of epinephrine (epi) in isolated, arterially perfused rabbit eyes. Pretreatment with Tween 80, Triton X 100, digitonin and sodium dodecyl sulphate (SDS) caused a dose-dependent reduction of epi induced vasoconstriction of uveal vessels. There also was a dose dependent reduction of the epi induced fall in intraocular pressure (IOP) after pretreatment with Tween 80 and Triton X-100; digitonin and SDS enhanced the effects of epi on IOP but these effects were not dose-dependent. Significant effects of all four detergents on the efficacy of epi were irreversible. Digitonin probably increased the affinity of epi for the adrenergic receptor as shown by the decrease of the ED50-value; the three other detergents did not significantly affect the affinity. The sequence of administration of epi and detergents is of minor importance for the effects of Tween 80 and Triton X-100 but differs significantly for the effects of digitonin and SDS. PMID- 4028803 TI - Calcium-binding characteristics of the EDTA-extractable proteins from calf lens fiber membranes. AB - The calcium-binding characteristics of the EDTA-extractable proteins (EEP) from calf lens fiber membranes were studied by equilibrium dialysis and far ultraviolet circular dichroism measurements. The EEP proteins appeared to contain binding sites with different affinities for calcium. These sites seem to behave as positively cooperating Ca2+ binding sites with a total capacity of 25 mol Ca2+ per mol EEP. The mean apparent dissociation constant (KD) for the Ca2+ binding sites was determined to be 7.7 microM. Calcium binding probably is accompanied by a decrease in the apparent alpha-helical content of the EEP proteins. The present results indicate that the EEP proteins belong to the group of proteins possessing high affinity and binding capacity for calcium. Because of the high calcium binding capacity, the EEP proteins possibly function as an intracellular calcium store in the lens. The calcium-sensitivity of the conformational state of the EEP proteins, however, might point to a possible regulating function of these membrane proteins in calcium-dependent cellular processes in the lens. PMID- 4028804 TI - Ocular tissues contain inhibitors of lymphocyte mitogenesis. AB - A fraction of bovine vitreous extract is a potent inhibitor of mitogen induced lymphocyte proliferation in vitro. Proliferation of lymphocytes induced in culture by lipopolysaccharide was more sensitive to inhibition by this fraction than were cultures of lymphocytes stimulated by Concanavalin A. We were unable to demonstrate such activity in similarly prepared fractions of cornea and lens. PMID- 4028805 TI - Comparison of the duration of antihypertensive action of atenolol and metoprolol over a 24-hour period. AB - The antihypertensive and beta-blocking effect of 100 mg atenolol and 100 mg metoprolol each given once daily were compared using an observer-blind, randomized, placebo-controlled crossover study. Blood pressure and heart rate were measured 22 hours after the last tablet of a 2-week dosing period. Twenty five patients completed the study. Both drugs caused a significant decrease in supine and standing blood pressure, with atenolol effecting, numerically, the greater reductions. The decrease in standing diastolic blood pressure was significantly greater with atenolol than with metoprolol (p less than 0.05). Metoprolol at 22 hours post-dosing did not differ from placebo in the control of exercise systolic blood pressure (191.1 v 194.6 mmHg): the exercise systolic blood pressure achieved on atenolol (177.3 mmHg) was significantly lower than that achieved on both placebo (p less than 0.001) or metoprolol (p less than 0.05). The heart rates achieved on atenolol were significantly lower than those achieved on metoprolol in similar circumstances (p less than 0.001). It is concluded that, at the doses examined in this study, atenolol is the more suitable agent for the control of supine, standing and exercise blood pressure over 22 hours. PMID- 4028806 TI - Administration of ketoprofen suppositories for out-patient post-operative analgesia. AB - A double-blind, randomized, placebo-controlled study was carried out to assess the efficacy of ketoprofen suppositories as a post-operative analgesic in out patients undergoing extirpation surgery. Thirty patients received 2 X 100 mg ketoprofen suppositories, and 30 patients received placebo suppositories 1-hour pre-operatively. Patients received no premedication and the anaesthetic used was intravenous diazepam and ketamine administered by intravenous drip according to the patient's need. Subjective symptoms of pain were evaluated 15, 30, 60 and 90 minutes post-operatively. None of the patients who received ketoprofen complained of post-operative pain, whereas the patients on placebo showed varying degrees of pain. The only side-effects recorded were nausea and vomiting both in ketoprofen and placebo-treated patients and these were probably related to the anaesthetic. PMID- 4028807 TI - A double-blind comparison of slow-release and standard tablet formulations of fentiazac in the treatment of patients with tendinitis and bursitis. AB - Two double-blind studies were carried out to compare the effectiveness and tolerance of a slow-release tablet formulation of 300 mg fentiazac, given once daily, with the standard tablet formulations of 100 mg, given 4-times daily, or 200 mg, given twice daily. A total of 60 patients suffering from acute bicipital tendinitis and/or subdeltoid bursitis was studied, 15 patients on the slow release and 15 on one of the two standard tablets in each of the two trials. Patients were assessed on entry and at Days 7 and 14 of treatment. The results in both studies showed that there was significant improvement in tenderness, pain on movement, overall pain and in the range of movement after treatment, there being no significant difference between those receiving the slow-release form or the standard tablets. Tolerance was good in all groups and only a few minor or moderate side-effects, mainly of a gastro-intestinal type, were reported. PMID- 4028808 TI - Comparative randomized study of cerebral blood flow after long-term administration of pentoxifylline and co-dergocrine mesylate in patients with chronic cerebrovascular disease. AB - The behaviour of regional cerebral blood flow was studied in 90 patients with vascular type dementia. Patients were divided at random into three groups of 30 and treated 3-times daily over a period of 8 weeks with either 400 mg pentoxifylline ('Trental' 400) or 2 mg co-dergocrine mesylate, or remained untreated (control group). Measurements of regional cerebral blood flow were made before and after 4 and 8 weeks of the study using an atraumatic inhalative 133Xenon clearance technique and assessments made in 16 regions of interest per hemisphere (grey matter perfusion). A statistically significant increase over baseline in mean regional cerebral blood flow was found in patients on pentoxifylline medication at Weeks 4 and 8. At Week 8, the change from baseline was +16.4% in the pentoxifylline group whereas the respective values for the other two groups were +0.4% for co-dergocrine mesylate, -2.4% for the controls. Hypoemic regions showed the most pronounced regional cerebral blood flow changes with pentoxifylline (+40%), the corresponding values for the co-dergocrine mesylate and control group being +10.8% and +0.4%, respectively. PMID- 4028809 TI - Albendazole in the treatment of intestinal helminthiasis in children. AB - A single dose of 2% albendazole suspension (400 mg in 20 ml) was administered to 77 patients (42 males and 35 females), ages ranging between 2 to 12 years, with helminthic infections. Ascariasis was the most prevalent infection. Patients were followed-up for 3 weeks. The results showed that albendazole was highly effective against Ascaris lumbricoides, Ancylostoma duodenale and Enterobius vermicularis. Significant improvement was also observed in patients having infections due to Trichuris trichiura. Albendazole was well tolerated and did not produce any significant side-effects. Single dose albendazole appears to be appropriate for mass chemotherapy to control intestinal nematode infections in highly infected communities. PMID- 4028811 TI - Management of major thoracic wall trauma. PMID- 4028810 TI - Sleep and wake after benzodiazepine hypnotics: a 20-hour EEG comparison of lormetazepam and flunitrazepam. AB - In an electropharmacokinetic study, the effects of lormetazepam and flunitrazepam were compared by the means of a sleep EEG and waking EEG during the following daytime. At a 1-week interval, 6 normal subjects received at random either 2 mg lormetazepam or 2 mg flunitrazepam in a double-blind, crossover fashion. Sleep EEG was recorded throughout the night; 6-min EEG samples were recorded every hour during 10 hours on the following daytime for spectral analysis. Night sleep after flunitrazepam showed lower Stage IV sleep than after lormetazepam. During daytime, only flunitrazepam induced an increased percentage of beta 2 frequencies, which remained above baseline up to 10 hours after awakening, indicating a prolonged impregnation time. This study permitted comparison of the relative intensity and duration of these two benzodiazepines: lormetazepam appeared to be a short-acting hypnotic while flunitrazepam displayed longer modification of the brain electrical activity. PMID- 4028812 TI - Invagination of the appendiceal stump for the reduction of peritoneal bacterial contamination. PMID- 4028814 TI - Baroreceptor pressure regulation after aortic occlusion. PMID- 4028813 TI - Naloxone improves myocardial perfusion in hypovolemic shock. PMID- 4028815 TI - Pulsatile left atrial-femoral artery bypass aids in limiting myocardial infarct size following reperfusion. PMID- 4028816 TI - Misadventures in surgical residency: analysis of mistakes during training. PMID- 4028817 TI - Associated injuries and alternatives in management of splenic trauma. PMID- 4028818 TI - Does the in-service training examination correlate with clinical performance in surgery? PMID- 4028819 TI - Reticuloendothelial function in the clearance of microaggregates following trauma. PMID- 4028820 TI - Air-blood barrier thickness and blood gas changes in sepsis. PMID- 4028821 TI - Complications of vascular access in a dialysis population. PMID- 4028823 TI - The biology of trypanosomes. PMID- 4028822 TI - The source of hepatic blood supply influences plasma amino acid patterns. PMID- 4028824 TI - Farewell address. PMID- 4028826 TI - Some neglected features of psoriatic lesions. PMID- 4028825 TI - Dimethyl sulfoxide as a vehicle for food allergy patch tests. PMID- 4028828 TI - Corrective cosmetics. PMID- 4028827 TI - Latrodectism: black widow spider bites. PMID- 4028829 TI - Capsule swallowing: the lean-forward technique. PMID- 4028830 TI - Subungual lentigo maligna. AB - A case of subungual lentigo maligna and a review of the literature is presented. Pigmented lesions involving the nail bed are rare, and should arouse clinical suspicion. Examination of biopsy specimens of these lesions is essential to rule out malignancy. The treatment of choice of lentigo maligna is surgical excision. PMID- 4028831 TI - Acquired ichthyosis in a patient with polycythemia rubra vera. AB - Acquired ichthyosis is known to be associated with a variety of systemic diseases and to occur secondarily to the intake of some drugs. A 57-year-old woman with acquired ichthyosis and polycythemia rubra vera is described. PMID- 4028832 TI - Diflorasone diacetate ointment 0.05 percent in conjunction with UVB and tar in a modified outpatient Goeckerman regimen. AB - Nineteen patients with psoriasis were treated with a modified Goeckerman regimen tailored to enhance patient compliance. Treatment consisted of daily coal tar emulsion baths at bedtime, followed by the application of 0.05 percent diflorasone diacetate ointment. Patients received increasing suberythemal dosages of short ultraviolet radiation (UVB) three times weekly at our outpatient phototherapy center. The duration of therapy ranged from three to twenty-eight weeks. The average number of phototherapy treatments was twenty-nine. Eight patients had total clearing of their lesions. Of the remainder, seven had at least 75 percent clearing and one had less than 25 percent clearing of psoriasis. One patient with psoriatic erythroderma experienced no improvement. Two patients did not complete the study. There were no side effects encountered during treatment other than periodic excessive erythema. If the two patients who did not complete the study are excluded from the results, 88 percent (fifteen of the remaining seventeen) had 75 percent or greater resolution of their psoriatic eruption and 47 percent (eight of seventeen) had total clearing. This outpatient modification of the Goeckerman regimen eliminates the use of cosmetically unacceptable topical agents during working hours, promotes patient compliance, and presumably contributes to enhanced therapeutic efficacy. PMID- 4028833 TI - Effects of mercury-selenium antagonism on mammalian cell division. AB - Various combinations of HgCl2 and sodium selenite were administered orally to rats and mice in vivo for both chronic and acute treatment. The antagonistic interaction and the optimum combination at which the action of HgCl2 could be neutralised by Na2SeO3 was investigated. Of the concentrations employed in rats when Na2SeO3 was fed after 1 h treatment with HgCl2, the percentage of chromosomal abnormalities significantly decreased as compared to animals treated with HgCl2 alone. All other experiments with different combinations of HgCl2 and Na2SeO3 gave higher frequencies of chromosomal abnormalities as compared to Na2SeO3 alone. An acute dose of HgCl2 was lethal, but in combination with Na2SeO3 at 1 h intervals, the abnormalities decreased to 60%. The results with mice showed antagonism in mixtures at higher doses, which was not evident in lower doses. PMID- 4028834 TI - Sex-influenced CPIB-induction of peroxisomes in rat liver and kidney tissues. AB - Male and female rats were used for CPIB-administered inducement of peroxisomes in liver and kidney tissues. Male rats respond to CPIB with higher levels of peroxisomal proliferation than females. Superoxide dismutase activity does not appear to be influenced by CPIB in any of the tissues studied. Aminotriazole depressed catalase activity in both males and females. PMID- 4028835 TI - Supernumerary chromosomal elements in lymphocytes cultured from phenotypically normal human adult males. AB - In a group of phenotypically normal men there were approximately 0.24% of metaphase lymphocytes with extra chromosomal elements along with the regular 46 chromosomes. They ranged in size from small acrocentric-acentric elements to elements longer than any chromosome arm. These elements have been referred to as supernumerary chromosomal elements. No significant effects due to donor's age, smoking history, season, storage of blood samples prior to culture, or culture medium, were found either in the frequency of supernumerary elements per cell or in the frequency of cells with supernumerary elements. Furthermore, the same subject did not consistently exhibit supernumerary elements. Furthermore, the same subject did not consistently exhibit supernumerary elements when sampled during four successive quarters of the year. Some of these elements in pairs were identified by G-banding technique as translocation chromosomes bearing long arms of chromosome number 2 and presumptive short arms of chromosome 8, acentric long arms of chromosome 4, and iso-acentric chromosomes for the long arms of chromosome 5. Presumably, more than one type of cytogenetic event occurred in their formation. Circumstantial evidence has been presented to show that the means of elimination of these supernumerary elements is a process of chromosomal disintegration. PMID- 4028836 TI - An ovarian chromosome map of Anopheles stephensi. AB - A polytene chromosome map of Anopheles stephensi has been prepared from the ovarian nurse cells of adult females. Many homologous regions can be recognized in comparisons between the ovarian and salivary gland chromosome maps but band for band homologies are not readily evident. The preparation of polytene chromosomes from ovarian nurse cells is easier than from the larval salivary glands and the results more consistent. PMID- 4028837 TI - Bronchoalveolar lavage for research purposes in the immunocompromised host. PMID- 4028838 TI - Sleep apnea: when does better become benefit? PMID- 4028839 TI - Dipyridamole thallium testing. An alternative form of stress testing in patients unable to exercise. PMID- 4028840 TI - Smoking cessation. PMID- 4028841 TI - Toxic-oil syndrome. Epidemic with an elusive etiology. PMID- 4028842 TI - Patients, clinicians, and the science of investigation. PMID- 4028843 TI - Safety of outpatient cardiac catheterization. AB - In this study, we compared the procedure-related complications of inpatient and outpatient cardiac catheterization when performed at the same institution by the same group of cardiologists. The majority of the studies were done using a brachial arterial cutdown approach. The mean age, sex, cardiac diagnosis, mean left ventricular ejection fraction, and the distribution of coronary arterial lesions were similar in both groups. There were relatively more patients in the New York Heart Association's class 4 in the inpatient group (p less than 0.01). In the outpatient group (676 patients), there were no major complications, and the rate of minor complications was 1 percent. In the inpatient group (1,106 patients), the rate of major complications was 0.4 percent and of minor complications 1.4 percent. The rates of major, minor, and total complications were statistically similar between the two groups. In the outpatient group the presence of left main coronary arterial disease, triple-vessel coronary disease, a left ventricular ejection fraction less than 30 percent, or a history of a recent myocardial infarction did not alter rates of complications. The hospital related cost of the procedure on an outpatient basis was 26 percent less than on an inpatient basis. Our findings indicate that outpatient cardiac catheterization, using a brachial cutdown approach, is safe even in a higher risk subgroup of patients and provides significant financial savings. PMID- 4028844 TI - Pulmonary cell populations in the immunosuppressed patient. Bronchoalveolar lavage findings during episodes of pneumonitis. AB - Bronchoalveolar lavage (BAL) cell populations were determined in 47 immunosuppressed patients during episodes of pulmonary disease. Thirty six patients had AIDS and 11 had conventional causes of immunosuppression. Pulmonary disease was due to a variety of infectious and noninfectious causes and was similar in both groups. In the AIDS patients, the mean BAL cell proportions were 64.2 +/- 3.7 percent alveolar macrophages (MACS), 28.7 +/- 3.4 percent lymphocytes, 3.5 +/- 1.8 percent polymorphonuclear cells (PMN) and 1.6 +/- 0.6 percent eosinophils (EOS). The non-AIDS group had similar findings in the BAL, with 59.3 +/- 8.3 percent MACS, 34.8 +/- 7.2 percent lymphocytes, 5.5 +/- 1.7 percent PMN and 0.4 +/- 0.2 percent EOS. The most striking finding in each group was a significant increase in both the proportion and absolute number of lymphocytes compared to controls. This was in marked contrast to the peripheral blood findings of lymphopenia. There was no characteristic cell profile diagnostic of any specific pulmonary disease. There was also no direct relationship of the cells present to respiratory symptoms, roentgenographic abnormalities or survival from pulmonary disease. This study demonstrates that although there was wide individual variation in lavage findings, a local pulmonary inflammatory reaction consisting predominantly of lymphocytes occurs in the immunosuppressed host during episodes of lung disease. The significance of this lymphocyte alveolitis and the complex host pathogen interaction responsible for determining the cell populations present in the lungs of these patients requires further study. PMID- 4028845 TI - Chest percussion and postural drainage in patients with bronchiectasis. AB - Patients with chronic obstructive pulmonary disease have been treated routinely with chest physical therapy for many years in spite of a lack of scientific validation of this procedure. Only recently have the indications for chest physical therapy been clarified. It is currently believed that such therapy is especially beneficial in patients with copious secretions, and that it is less effective in patients with scanty secretions. No study has specifically evaluated the efficacy of chest physical therapy in patients with bronchiectasis. We accordingly evaluated 13 patients with stable bronchiectasis to determine the effects of chest physical therapy on pulmonary function, arterial oxygenation, and sputum production and to assess whether this therapy was associated with any significant side-effects. We found that chest physical therapy was safe and well tolerated and assisted the patients in mobilization of their sputum. However, such therapy had no immediate delayed effects on pulmonary function or oxygen saturation. PMID- 4028846 TI - Lung sound analysis for continuous evaluation of airflow obstruction in asthma. AB - We developed a system for monitoring airflow obstruction noninvasively, based on the principle that the proportion of the breath cycle occupied by wheezing (Tw/Ttot) in any one subject corresponds to the severity of airways obstruction. Lung sounds were recorded continuously from the chest wall. Fifty 250 ms sound segments were randomly chosen from five-minute periods and analyzed for the presence or absence of wheezes. The proportion with wheezes was used as an estimate of Tw/Ttot (Est Tw/Ttot). For 12 wheezy patients, there was a good correlation between the Est Tw/Ttot and the forced expiratory volume in one second (r = 0.893, p less than 0.001). The system was used to evaluate nocturnal asthma. Five subjects were studied over eight nights. It was found that there was more wheezing from 4:00 to 4:30 AM than from midnight to 12:30 AM (p less than 0.05). This technique may prove useful in continuous, noninvasive monitoring of wheezy patients. PMID- 4028847 TI - Site of airflow obstruction during early and late phase asthmatic responses to allergen bronchoprovocation. AB - Chronic asthma and late asthmatic responses (LAR) are associated with local inflammation which might be expected to produce airflow obstruction in small airways and to increase nonspecific airway reactivity. In contrast, early asthmatic responses (EAR) are primarily bronchospastic and probably involve more central airways. We challenged 17 nonsmoking, mildly asthmatic atopic subjects with allergen bronchoprovocation and measured changes in spirometry (FEV1) over the next 24 hours. Each subject also performed a helium-oxygen (He-O2) flow volume loop before challenge (baseline), during the EAR, and six hours and 24 hours after challenge to measure the effect of gas density on flow rates at midvital capacity. Twelve subjects had both an EAR and a LAR; five subjects had only a LAR. Of these 17 subjects, 15 were initially density dependent, while only two were density independent. During the EAR, 13 percent of the density dependent population had significant decreases in delta Vmax 50 percent; 47 percent had significant decreases during LAR. The He-O2 flow data analyzed at specified time points after challenge revealed significant decreases in the mean delta Vmax 50 percent at six hours in those who had only a LAR (p less than 0.01). In those who had a dual airway response, density dependence increased during the EAR, but decreased at six and significantly at 24 hours (p less than 0.05) postchallenge. There was a strong trend for the severity of the LAR (measured by changes in FEV1) to be directly related to the total decrease in delta Vmax 50 percent during the LAR. We conclude that late asthmatic responses occur frequently after a single antigenic bronchial challenge and can be associated with persistent symptoms. The LAR were often associated with a decrease in density dependence of maximal expiratory airflow, and therefore, may involve small airways. PMID- 4028849 TI - Uvulopalatopharyngoplasty. One-year followup. AB - Uvulopalatopharyngoplasty (UPPP), originally evaluated in 66 patients with objectively documented sleep apnea syndrome, was successful in 33 of the patients as indicated by clinical and polysomnographic improvements. One-year followup polysomnographic evaluations were obtained in 20 of these patients; the remaining 13 were lost to followup. After one year, the patients maintained the improvements seen at the six-week evaluation. Frequency and duration of apnea was significantly reduced from presurgery levels and similar to the six-week results. Oxygenation measures also did not differ from the six-week results, remaining better than presurgery values. Thus, respiration did not disrupt sleep to the degree it had before surgery. Sleep measures were improved compared to presurgery and similar to the six-week data. Body weight remained stable over the entire period. PMID- 4028848 TI - Reactive airways dysfunction syndrome (RADS). Persistent asthma syndrome after high level irritant exposures. AB - Ten individuals developed an asthma-like illness after a single exposure to high levels of an irritating vapor, fume, or smoke. In most instances, the high level exposure was the result of an accident occurring in the workplace or a situation where there was poor ventilation and limited air exchange in the area. In all cases, symptoms developed within a few hours and often minutes after exposure. We have designated the illness as reactive airway dysfunction syndrome (RADS) because a consistent physiologic accompaniment was airways hyperreactivity. When tested, all subjects showed positive methacholine challenge tests. No documented preexisting respiratory illness was identified nor did subjects relate past respiratory complaints. In two subjects, atopy was documented, but in all others, no evidence of allergy was identified. In the majority of the cases, there was persistence of respiratory symptoms and continuation of airways hyperreactivity for more than one year and often several years after the incident. The incriminated etiologic agent varied, but all shared a common characteristic of being irritant in nature. In two cases, bronchial biopsy specimens were available, and an airways inflammatory response was noted. This investigation suggests acute high level, uncontrolled irritant exposures may cause an asthma like syndrome in some individuals which is different from typical occupational asthma. It can lead to long-term sequelae and chronic airways disease. Nonimmunologic mechanisms seem operative in the pathogenesis of this syndrome. PMID- 4028850 TI - Toxic-oil syndrome. Gallium-67 scanning and bronchoalveolar lavage studies in patients with abnormal lung function. AB - The toxic-oil syndrome (TOS) is a multisystem disorder whose etiology and pathogenesis are as yet unknown. Lung alterations persist in a significant number of TOS patients due to the underlying vascular lesion. Computer-assisted 67Ga scanning and bronchoalveolar lavage (BAL) studies were performed in 14 TOS patients with sustained abnormal diffusing capacity for carbon monoxide (Dco). No significant difference was observed between the 67Ga uptake index of the TOS and control populations. Likewise, there was no significant difference in the number of effector cells recovered from the lungs of TOS patients and controls by bronchoalveolar lavage. However, a rise in IgA and IgG concentrations (p less than 0.002) and a fall in alpha 1-antitrypsin (p less than 0.05) and transferrin (p less than 0.01) were observed in the TOS group. Phospholipid and lecithin concentrations in the lavage fluid were similar for patients and controls. The alveolar macrophage function assayed in three TOS patients was normal. These observations raise new questions about the outcome of lung pathology in TOS and warrant further follow-up studies of the lung abnormalities observed. PMID- 4028851 TI - Electrocardiographic and vectorcardiographic diagnosis of posterior wall myocardial infarction. Significance of the T wave. AB - The electrocardiographic diagnosis of posterior wall myocardial infarction remains elusive. To determine discriminating criteria a group of 27 patients with posterior infarction proven by biplane angiocardiography were compared to 97 controls. All patients had single-vessel obstruction of the circumflex artery or one of its major branches (greater than or equal to 75 percent area stenosis) without occlusive disease in the other coronary arteries. High-frequency, high gain electrocardiograms and Cube and McFee vectorcardiograms were analyzed. Pathologic Q waves in the inferior leads were present in only 22 percent (six) of the patients; increased R-wave amplitude or duration in the right precordial leads was found in 17 to 26 percent, and an R/S ratio greater than or equal to I in lead V1 or greater than or equal to 1.5 in lead V2 was present in 22 percent (six) of patients. Vectorcardiographic criteria which improved the diagnostic yield were: (1) the presence of a QRS loop mostly anterior to the E point, and (2) the presence of an abnormally anterior T wave. This abnormal T-wave shift was present in over 70 percent of the patients with posterior infarctions and was clearly discernible from the 12-lead ECG, as manifested by tall T waves in lead V2 and flat T waves in lead V6. To approximate the T-wave angle in the 12-lead scalar ECG, an index was calculated by subtracting the amplitude of the T wave in lead V6 from its amplitude in lead V2 (T2-T6 index). An index of 0.38 mV or more yielded a sensitivity of 81 percent and a specificity of 75 percent; however, this was not as discriminating as the vectorcardiogram where a T angle of 60 degrees or more in the horizontal plane yielded a sensitivity of 70 percent and a specificity of 97 percent. PMID- 4028852 TI - Changes in the pulmonary glucocorticoid receptor content in the course of interstitial disease. AB - The level of cytosolic glucocorticoid receptors (GR) was measured in 12 open chest lung biopsies of interstitial pulmonary diseases. The results showed an increase in the GR content in the diseased lungs correlated to the degree of septal cellularity in nine cases. Two pulmonary sarcoidosis and one end-stage idiopathic pulmonary fibrosis patients presented higher levels of GR than those predicted by the septal cellularity. It was concluded that the GR content of the lungs increases in the course of interstitial diseases, reflecting the number of cells that express cytosolic GR in pulmonary parenchyma. PMID- 4028853 TI - Measurement of tidal breath by determination of chest wall volume displacement in patients with airflow obstruction. AB - We compared tidal volume (VT) measured from the integrated airflow signal of a pneumotachygraph (PNTG) in ten patients, seated comfortably, with airway obstruction to VT, recorded simultaneously, by three chest-wall volume displacement methods: two-channel magnetometer, isovolume calibration (mag-isov); respiratory inductance plethysmograph, isovolume calibration (rip-isov); and, inductance plethysmograph, least squares calibration (rip-l sq). There was no difference between VT, measured without PNTG, with each of the methods. When mouthpiece, noseclips, PNTG, and finally, dead space were included in a breathing circuit, VT increased to approximately one and one-half times that measured without the mouthpiece. Inspiratory volumes were measured with similar error by each method (mag-isov, 8.61 +/- 5.73 percent SD; rip-isov, 9.30 +/- 6.12 percent SD; rip-l sq, 8.43 +/- 6.27 percent SD). We conclude that in airway obstruction patients seated in a constant position, over the range of inspiratory volumes studied, error associated with chest wall volume-displacement methods is no greater than in normal subjects. PMID- 4028854 TI - Chyliform (cholesterol) pleural effusion. AB - Chyliform pleural effusions are a little known occurrence only sparingly reported in the literature. At the lung department in Uppsala, Sweden, 11 cases have been seen the last few years. Typically, the exudate develops in a long-standing pleural thickening resulting from therapeutic pneumothorax many years earlier. The exudate contains a high level of cholesterol, probably breakdown products from blood cells. It is usually sterile, and only very rarely can one find tubercle bacilli growing from it. There is a tendency toward recurrence. If the patient benefits clinically from aspiration of the fluid, decortication is indicated. PMID- 4028856 TI - Are active and passive smoking harmful? Determining causation. AB - Assessing the evidence regarding any causal question involves examining the strength of the studies conducted and applying a series of "diagnostic tests" for causation. We have reviewed the strength of the evidence incriminating smoking as a cause of lung cancer, and passive smoking as a cause of respiratory illness and decreased pulmonary function in children. There are eight prospective studies of smoking and lung cancer which have consistently shown a strong relationship. These studies have confirmed the temporality of the association and demonstrated a dose-response gradient. The studies addressing the effects of passive smoking in children are considerably weaker. Although they are consistent in suggesting increased infections for children less than one year of age, neither increased risk nor a dose-response gradient is consistently found in older children and the effect size, when present, is small. The rules for assessing causation applied here can be used to integrate new information concerning the health hazards of smoking. PMID- 4028855 TI - Effects of noradrenaline and isoproterenol on cardiopulmonary function in a canine model of acute pulmonary hypertension. AB - The authors investigated acute cardiopulmonary effects of noradrenaline and isoproterenol infusion in a canine model of increased pulmonary vascular resistance (PVR) and decreased cardiac output (CO). In six anesthetized, ventilated dogs, autologous blood clots were injected over approximately two hours to increase right ventricular (RV) afterload and decrease CO. After CO had decreased 40 percent dogs were treated with noradrenaline or isoproterenol in alternate sequence. Both drugs increased stroke volume but only isoproterenol affected CO. Flow increased from 1.3 to 3.0 L X min-1 (p less than .01) with isoproterenol infusion. Corresponding to the increase in CO, RV filling pressure and PVR decreased, from 9 to 5 mm Hg, and from 36 to 16 mm Hg X L-1 X min (p less than .01) respectively. When a moderate decrease in CO complicates an acute increase in PVR, isoproterenol may be an excellent drug to treat the decrease in flow. PMID- 4028857 TI - Marfan's syndrome presenting as a type 3 aortic dissection. PMID- 4028858 TI - Metastatic squamous cell carcinoma to the heart. Unusual cause of angina decubitus and cardiac murmur. AB - A 61-year-old woman was admitted to the hospital with the new onset of angina at rest and an ECG consistent with anterior wall ischemia. She was also noted to have a new cardiac murmur. Eighteen months earlier, she had been treated for squamous cell carcinoma of the base of the tongue. Thirteen months ago, she had local recurrence treated with radiotherapy, but had no evidence of recurrent or metastatic disease at the time of present admission. Echocardiography revealed intracardiac and extracardiac masses; surgical biopsy confirmed metastatic carcinoma to the heart which was responsible for her symptoms and the new murmur. Symptomatic cardiac metastases from squamous cell carcinoma is an unusual situation which, in this case, was easily diagnosed with echocardiography. PMID- 4028859 TI - Pseudo-pseudo-pseudotumor of the lung. AB - Benign lesions may simulate bronchogenic carcinoma by virtue of radiologic appearance or false-positive cytologic studies. A lung opacity initially suspected to be malignant was, on review, considered to be a loculated effusion. Needle biopsy yielded cells which appeared malignant. The resected lesion was a benign infarct. PMID- 4028860 TI - Ostial left main stenosis following repair of a ruptured sinus of Valsalva aneurysm. AB - A patient complained of angina pectoris nine months after surgical repair of an aortic right atrial fistula and mitral valve replacement. Subsequently, he was shown to have a new obstruction of the ostium of the left main coronary artery. This case illustrates the need to consider this syndrome in the differential diagnosis of postoperative complaints of chest pain, especially following an operation which involves direct cannulation of the coronary arteries. PMID- 4028861 TI - Pulmonary lymphangiomyomatosis associated with tuberous sclerosis. Treatment with tamoxifen and tetracycline-pleurodesis. AB - A 44-year-old woman was seen with the clinical and histologic picture of lymphangiomyomatosis syndrome. She also had dermatologic and neurologic stigmata of tuberous sclerosis. After the development of a recurring chylothorax, she had a downhill course unresponsive to dietary, bronchodilator, corticosteroid and progesterone therapy. In an open lung specimen, the search for steroid receptor for estrogen was positive. The discovery in this case of an estrogen receptor represents important evidence for establishing an association between tuberous sclerosis and lymphangiomyomatosis. Tamoxifen therapy and tetracycline pleurodesis were successful in stopping the progressive course and controlling the chylothorax. PMID- 4028862 TI - Massive hemoptysis associated with foreign body removal. AB - Exsanguinating hemoptysis accompanied removal of an endobronchial foreign body in a 12-year-old child. Preparations to treat this complication should be made prior to removal of any foreign body of prolonged sojourn in the tracheobronchial tree. PMID- 4028864 TI - "Saw-tooth" pattern in the flow-volume loop. PMID- 4028863 TI - Dissecting aneurysm of the ascending aorta with aorto-caval fistula. Fiberoptic oximetric findings and surgical management. AB - A patient presented the rare complication of a dissecting aneurysm of the ascending aorta ruptured into the superior vena cava producing a left-right fistula. Continuous oximetric measurements by a fiberoptic pulmonary artery floated catheter was used to localize the site of the shunt. Emergency surgical repair was successfully performed. PMID- 4028865 TI - Preventing PPC. PMID- 4028866 TI - Bronchoscopy in patients with gastroparesis. PMID- 4028867 TI - Medical decisions in a context of conflicts. PMID- 4028868 TI - Legal issues in withholding or withdrawing medical treatment. PMID- 4028869 TI - Diagnostic imaging in hypertension. PMID- 4028870 TI - Comparative pharmacokinetics of ceftriaxone after subcutaneous and intravenous administration. AB - The pharmacokinetics of ceftriaxone (CRO) after subcutaneous and intravenous administration was studied in 10 healthy volunteers (5 males, 5 females, age 22 43 years, body weight 64.3 +/- 9.5 kg). Each of them received 2.0 g CRO i.v., and then 0.5 g i.v. and 0.5 g CRO s.c. in a randomized cross-over design. Subcutaneous administration of ceftriaxone was tolerable in combination with lidocaine. Serum and urine concentrations were determined by high performance liquid chromatography and for comparison with a bioassay. Mean serum concentrations were high after intravenous administration: 258 +/- 40 mg/1 (0 min, 2 g i.v.) resp. 84 +/- 40 mg/1 (0 min, 0.5 g i.v.). They declined to 11.6 +/ 4.2 mg/1 (2 g) resp. 6.5 +/- 2.2 mg/1 (0.5 g i.v.) within 24 h. Following subcutaneous application peak serum concentrations of 37.1 +/- 5.6 mg/1 were found after 138 +/- 49 min and a mean serum concentration of 6.6 +/- 1.6 mg/1 after 24 h. Concentrations of free ceftriaxone, determined by ultrafiltration, were 9.2 +/- 2.7% of total concentrations from 25 to 200 mg/1. Cumulated urine recoveries over a period of 24 h were: 51.2 +/- 8.9% (2 g i.v.), 47.1 +/- 7.9% (0.5 g i.v.) and 39.7 +/- 9.5% (0.5 g s.c.). There was no evidence for the presence of a microbiologically active metabolite in urine. Comparison of pharmacokinetic parameters for the 0.5 g dose did not show relevant differences between intravenous and subcutaneous administration (using an open two compartment model): t beta 1/2 (min) 514 +/- 104 (s.c.), 592 +/- 133 (i.v.), VD,Area (1) 11.9 +/- 3.8 (s.c.), 13.3 +/- 3.8 (i.v.) and AUCtot (mg X h/1) 515 +/ 106 (s.c.) and 549 +/- 125 (i.v.). Bioavailability of the subcutaneous application was 0.96 +/- 0.26. For the 2 g i.v. dose the known nondosis-dependent kinetics was observed. Subcutaneous administration of ceftriaxone appears to be a possible alternative to the intravenous route in selected clinical situations or cases. PMID- 4028871 TI - Pharmacokinetics of lymecycline and doxycycline in serum and suction blister fluid. AB - In an open, random, cross-over trial, 8 young healthy volunteers were given standard doses of lymecycline and doxycycline for 2 days to achieve steady state. The pharmacokinetics of each tetracycline in serum and dermal, suction blister fluid were determined after oral doses of 300 mg lymecycline or 100 mg doxycycline on the 3rd day. Serum concentrations were higher for lymecycline than for doxycycline, the difference being statistically significant from 3 to 9 h after dosing. Also blister concentrations were higher for lymecycline than for doxycycline, though the difference was not statistically significant. The serum half-life for lymecycline was close to 10 h, for doxycycline 12 h. According to our results, both lymecycline and doxycycline should be regarded as 'intermediate acting' tetracyclines, and each should consequently be dosed twice daily. PMID- 4028872 TI - Biliary elimination of apalcillin in cholecystectomized patients. AB - Pharmacokinetic examinations were performed in 5 patients with bile-duct drainage following cholecystectomy and choledochus revision with 2 g of apalcillin over 20 min intravenously. In comparison to healthy volunteers they had significantly longer half-life values and long persisting serum concentrations over a period of 24 h. The biliary elimination rate of apalcillin correlated with the hepatic function of the patients and was with 4.3% on the average distinctly lower than that of healthy volunteers, whereby the bile, however, could probably not be collected quantitatively in cases of open papilla. Compensatory excretion of apalcillin took place via the kidneys and, considering the metabolites A1 and A2, it amounted to a total of 73%. PMID- 4028873 TI - Relative antibacterial efficacy of clindamycin and metronidazole against Bacteroides fragilis in vitro and in experimentally infected mice. AB - The antibacterial activity of clindamycin and metronidazole against Bacteroides fragilis was quantitated in vitro by MIC determination and colony counting at 24 h and in vivo from the effects on an experimental B. fragilis infection in mice; this infection was established after co-inoculation of B. fragilis and Escherichia coli. In vitro, clindamycin was 8 to 16 times more effective than metronidazole in terms of MIC values, and more than 30 times according to colony counts at 24 h. In vivo clindamycin was almost 8 times less effective than metronidazole according to dose. This was partly due to its less favorable pharmacokinetic properties, but clindamycin was still only 1.6 times more effective than metronidazole according to free plasma concentrations. In vivo neither clindamycin nor metronidazole had any antibacterial effect against E. coli. The discrepancy between the in vivo and in vitro results for B. fragilis is discussed. PMID- 4028874 TI - Synergistic antiviral effects of acyclovir and vidarabine on herpes simplex infection in newborn mice. AB - 277 5-7-day-old white Swiss mice were infected intranasally with Herpes simplex virus type 2 (HSV2) to mimic disseminated herpetic infection in human newborns. The antiviral efficacy of acyclovir, vidarabine and specific antiserum (SAS) alone and in combination was assessed. A significant increase in survival rate (52%) was observed with the combination of acyclovir (80 mg/kg/day) and vidarabine (125 mg/kg/day) compared to either compound (24 and 6%, respectively) when therapy was begun 30 h after infection and continued daily for the next 4 days. Combinations of acyclovir, vidarabine and SAS had less protective effect (8%) than acyclovir with SAS (32%) or vidarabine with SAS (12%). No improvement was observed in survival rate of HSV2-infected mice treated with SAS as compared with controls (0% and 5%, respectively). These results suggest the enhanced antiherpes effect in newborn mice is due to synergism of acyclovir and vidarabine, a combination deserving further evaluation for the treatment of HSV2 infections in humans. PMID- 4028875 TI - Variation in microbial survival and growth in intravenous fluids. AB - The survival and growth of aerobic and anaerobic bacteria, as well as a yeast, was studied in intravenous fluids over a 3-day period. Solutions were experimentally contaminated with pathogenic strains of Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, Bacteroides fragilis and Candida albicans. Samples of these solutions were tested on each day up to 3 days for determining viable numbers of the organisms by a membrane filtration method. Each organism showed a different survival/growth pattern in various infusion fluids. In 5% dextrose, C. albicans multiplied but only 2-3% of the initial viable cells of E. coli, P. aeruginosa, and S. aureus were detected after 3 days. In 0.9% sodium chloride, C. albicans and S. aureus showed growth and E. coli remained viable, but P. aeruginosa was not detected after 72 h. In lactated Ringer's solution, P. aeruginosa and C. albicans grew but E. coli and S. aureus were not detected after 72 h. In the amino acid solution, C. albicans, S. aureus and E. coli grew but P. aeruginosa and B. fragilis were not detected. Results indicate that the pattern of microbial survival and growth may be substantially different in various intravenous fluids. PMID- 4028876 TI - Learning impotence and the Peter Pan fantasy. PMID- 4028877 TI - Interparental ratings of temperament for high and low risk infants. PMID- 4028878 TI - From pediatrician to therapist--a bridge to cross. PMID- 4028880 TI - Study of a diagnostic profile of the borderline syndrome in childhood and trends in treatment outcome. PMID- 4028879 TI - Emotionally disturbed, adopted, inpatient adolescents. PMID- 4028881 TI - Teenage mothers. PMID- 4028882 TI - Bridging the gap between hospital and home. PMID- 4028883 TI - Inhalant abuse: an emerging problem among Mexican American adolescents. PMID- 4028884 TI - Working with families who donate organs and tissues. PMID- 4028885 TI - Nurses provide more than health care. Migrant workers clinic. PMID- 4028886 TI - Operating a primary prevention program. A blueprint for survival. PMID- 4028887 TI - [The peritoneum. Anatomical bases]. PMID- 4028888 TI - [Pathologic-anatomic relations between peritonitis and sepsis]. PMID- 4028889 TI - [Modified partial duodenopancreatectomy with preservation of the stomach, proximal gastric vagotomy and pancreatic duct occlusion]. AB - From 1979 till 1984 a modified partial duodenopancreatectomy was performed in 22 patients with preservation of the stomach, proximal gastric vagotomy, and occlusion of the pancreatic duct. If occlusion of the duct was performed without a pancreatojejunostomy 6 of 12 patients developed a spontaneously healing pancreatic fistula. In 10 patients with duct occlusion and a pancreatojejunostomy no fistulae were observed. Exocrine and, if necessary, endocrine pancreatic insufficiency could be compensated sufficiently medically and by diet. In comparison to the original Whipple's operation preservation of the stomach seems to influence favourably the body weight and thus the quality of life. The proximal gastric vagotomy is performed to prevent anastomic ulcers. PMID- 4028891 TI - [Is rigid rectoscopy obsolete?]. AB - Flexible fiberoptic sigmoidoscopy more and more replaces sigmoidoscopy with a rigid tube. In a retrospective series of 152 rigid sigmoidoscopies we analysed depth of endoscopy and findings. In 36% of patients without anaesthesia endoscopy had to be stopped at 15 cm and in further 31% at 20 cm leading to a highly significant difference to the anesthetized patients (p less than 0.0005). A good history of the present illness allows separating of bleeding carcinoma and polyps proximal to the sigmoid colon which have to be examined by colonoscopy. In routine screening for blood loss per anum it is desirable to achieve in all patients a maximal security not to overlook a finding, because of the medical costs. We have enlarged the list of indications for the rigid sigmoidoscopy by Marks et al. as a practical compromise: delineation of rectal lesions, side localization and critical rectal measurements, surveillance of disease states or anastomoses within its reach, for performing rectal biopsy and rectal polypectomy, in patients with possible contamination of the instrument, endoscopy in the anesthetized patient before a proctological operation if case history excludes a higher sited lesion. In all other cases there is an indication for colonoscopy or barium contrast enema. It is stressed that in patients with blood loss per anum the search for the source always is done by flexible fiberoptic sigmoidoscopy. PMID- 4028890 TI - [Correlation of clinical and computed tomographic findings for therapy and prognosis of acute pancreatitis]. AB - A prospective study was performed in 156 patients with acute pancreatitis to find out the value of computed tomography for the diagnosis and early prognosis. The CT finding leads to a diagnosis and differentiation in 3 risk groups similar to the clinical staging. The prognostic value of CT depends on the reproducible grading of pancreatic swelling and the grade of extrapancreatic fluid collections. CT finding correlates with early prognostic factors and the clinical staging, leading to different risk groups which allows an adequate stage depending therapy of patients with acute pancreatitis. PMID- 4028892 TI - [Stable, distraction-free wire cerclage]. PMID- 4028893 TI - [Free perforation of the colon in Crohn disease]. PMID- 4028894 TI - [Multiple liver abscesses--a rare complication of Crohn disease]. PMID- 4028895 TI - [Preoperative vascular control of the splenic pedicle in high-risk splenectomy. Experience in 3 cases]. PMID- 4028896 TI - [Nodular recurrence after thyroid surgery, excluding cancer]. PMID- 4028897 TI - [Darier-Ferrand dermatofibrosarcoma. Study of 96 cases over 15 years]. PMID- 4028898 TI - [Somatization. A surgical emergency to be recognized]. PMID- 4028899 TI - [Metastatic pulmonary hydatidosis of inferior vena cava origin. Apropos of a case]. PMID- 4028900 TI - [Secondary amputation of the rectum for neoplastic recurrence after rectal resection. Personal experience in 11 cases]. PMID- 4028901 TI - [Actuarial study of 148 thyroid papillary cancers]. PMID- 4028902 TI - [Aorto-ilio-femoral venous grafts. 66 cases. 60 surgically treated patients]. PMID- 4028903 TI - [Cancer of the rectum. Clinical and anatomopathological study and factors in survival]. PMID- 4028904 TI - [Extension to the trachea of pneumonectomies for bronchial cancer. Apropos of 46 cases]. PMID- 4028905 TI - Ethanol pharmacokinetics in healthy man: Michaelis-Menten parameters and the circadian rhythm. AB - Eleven presumed healthy subjects ingested in random order 3 different doses of ethanol (0.4, 0.6, 0.8 g X kg body weight-1) at 4 different times of day (0600, 1200, 1800, 0000). The rates of ethanol metabolism were measured by calculating the rate of decline of the linear portion of a plot of urinary concentration of ethanol against time (making correction for the ratio of ethanol in blood and urine). The rate of metabolism depended upon the dose of ethanol ingested and the peak concentration of urinary ethanol. The results lend further support to the view that the metabolic removal of ethanol can be described by Michaelis-Menten kinetics. Estimates of the Michaelis-Menten parameters Km and Vmax were made by considering the curvilinear portion of the decay curve at low concentrations. The values of these varied with time of ethanol ingestion; in particular, variation in Vmax can substantially account for the circadian rhythm of ethanol metabolism that had been measured previously. PMID- 4028907 TI - Diagnosis of ulcerative colitis in absence of classical typical clinical signs and/or histological findings. PMID- 4028906 TI - Copper and zinc level in biological samples from healthy subjects of vegetarian food habit in reference to community environment. AB - Many epidemiologists have found a correlation between copper and zinc in the community environment and diseases, such as myocardial and vascular pathologies, and diabetes. The purpose of this study was to investigate the total daily intake of these two metals in cooked food, drinking water and air and their respective levels in blood and urine. A chronobiological methodology has been adopted to establish the reference values of these two metals in biological samples. It has been observed that the daily intake of copper is within the recommended value, whereas its urinary excretion is high. The daily intake of zinc is below the recommended value and its urinary excretion is also high. Both the metals showed a temporal oscillation pattern in blood and urine. A possible chronic zinc deficiency has been anticipated in this particular ethnic group of vegetarian food habit. PMID- 4028908 TI - Effects of exogenous secretin on pancreatic and biliary ductal and sphincteric pressures in man demonstrated by endoscopic manometry and correlation with plasma secretin levels. AB - An endoscopic manometric technique was used to investigate the effects of exogenous secretin on pancreatic duct, common bile duct, pancreatic duct sphincter, and bile duct sphincter pressures in 20 healthy volunteers. Synthetic secretin was infused intravenously at rates of 8.05, 16.1, 32.2, 64.4, 129, 258, and 516 ng/kg/hr, and plasma secretin concentrations were measured by a radioimmunoassay. Secretin produced a significant fall in peak and trough pancreatic duct sphincter pressures from basal values of 48.2 +/- 7.9 mm Hg (mean +/- SD) and 16.9 +/- 7.7 mm Hg, respectively, to 34.4 +/- 6.8 mm Hg and 11.2 +/- 5.8 mm Hg (P less 0.005), respectively, at a mean plasma secretin concentration of 16 pg/ml (during an infusion rate of 32.2 ng/kg/hr). Higher infusion rates had no additional effect. Pancreatic duct pressure became significantly elevated above basal (11.5 +/- 4.0 mm Hg) at the two highest secretin rates. Secretin had no effect on common bile duct or bile duct sphincter pressures. Plasma secretin concentrations were within the postprandial range during the lowest four secretin infusion rates. We conclude that secretin produces selective physiological relaxation of the pancreatic duct sphincter. PMID- 4028909 TI - Pancreatic phlegmon. Clinical features and course. AB - The clinical course of 19 patients with pancreatic phlegmon, as diagnosed by computed tomography (CT) and clinical criteria, was assessed retrospectively and compared to that of eight patients with pancreatic abscess diagnosed either at surgery or with percutaneous aspiration. Controls consisted of 55 patients with uncomplicated acute pancreatitis without CT scans and 11 patients with acute pancreatitis in whom CT scans were negative or only consistent with acute pancreatitis (no phlegmon). The age, sex, and presumed etiology of the pancreatitis were not significantly different in the four groups. Patients with phlegmon had a higher incidence of severe pancreatitis as defined by Ranson's criteria, presence of an abdominal mass, as well as a longer duration of fever, abdominal pain and leukocytosis than controls without CT scans. With the exception of a palpable abdominal mass and fever lasting over five days, the results were similar when comparing the phlegmon group and controls with CT scans, although the severity of the disease and prolonged abdominal pain tended to be increased in the former patients. There was no statistically significant difference in clinical or laboratory criteria between the phlegmon and abscess groups, although the latter group had longer hospital stays and periods with no oral intake (npo). Management of patients with phlegmon tended to include TPN, longer npo periods, antibiotics, and longer hospital stay than in controls without CT scans. Controls with CT scans were managed similarly to the phlegmon group because of prolonged amylase elevation and abdominal pain. Percutaneous aspiration was successful in differentiating abscess from phlegmon in five of six cases. Major complications were rare in the phlegmon group and spontaneous resolution was the rule. Pancreatic phlegmon is a distinct clinical/radiologic entity which may be very difficult to differentiate clinically from pancreatic abscess. Early percutaneous thin-needle aspiration of the inflammatory mass (under CT guidance) seems to be the diagnostic procedure of choice. Management is nonsurgical unless complications arise. The role of TPN and antibiotics is unknown, and controlled studies of these therapeutic approaches in pancreatic phlegmon are needed. PMID- 4028910 TI - Gastroesophageal sphincter pressure and histological changes in distal esophagus in patients with achalasia of the esophagus. AB - A prospective study was performed in 17 patients with achalasia of the esophagus determining the manometric characteristics of the gastroesophageal sphincter, correlating it with histological analysis by biopsies taken during surgery at the distal narrowed segment of the esophagus, at the location of the sphincter. The histological findings were compared to 10 control cases. Presence or absence of ganglion cells at the Auerbach's plexuses and appearance of smooth muscle fibers were evaluated. Only one case (6%) had Chagas' disease. The mean sphincter pressure was 41 mm Hg, with incomplete relaxation in all patients. Histological analysis showed a complete disappearance of ganglion cells in 94% of the cases and a decrease in the number of neurons with marked chronic inflammatory cells in one case (6%). In all control cases, the ganglion cells were normal. Smooth muscle fibers were normal on light microscopy. No relationship was found between resting gastroesophageal sphincter pressure, length and relaxation, and histological findings at the distal esophagus. These findings suggest that the denervation in the majority of cases is located in the Auerbach plexus, with complete absence of ganglion cells and, therefore, absence of postganglionic nerve fibers. PMID- 4028911 TI - Effect of vagal blockade on food- and hormone-stimulated release of pancreatic polypeptide and motilin in dogs. AB - Vagal control of food- and hormone-stimulated release of pancreatic polypeptide (PP) and motilin was investigated in four conscious dogs by examining the effect of cryogenic vagosympathetic blockade. The postprandial PP response of 189 +/- 7 pM was totally, although reversibly, inhibited to 58 +/- 11 pM with the vagi blocked. Similarly, bombesin-, CCK-OP-, or neurotensin-stimulated PP release was abolished. Although the PP response to intraduodenal perfusion of an elemental diet was also reduced by blockade, the 52 +/- 15% inhibition was less than observed with the meal. In contrast to PP, plasma motilin fell after the meal from a fasting level of 128 +/- 16 pM to a nadir of 52 +/- 7 pM. Vagal blockade reversed this decline as plasma motilin rose to a peak of 121 +/- 18 pM with a pattern resembling the motilin response in the interdigestive state. This motilin increment during blockade was inhibited by atropine and by infusion of porcine PP. Plasma motilin also fell with the elemental diet, but this response was not affected by blockade. During infusion of bombesin, plasma motilin rose by 60 +/- 9 pM; vagal blockade augmented this increment twofold. Thus, the PP response to a meal and to hormonal stimulation is controlled by a vagal cholinergic excitatory pathway. However, intestinal release of PP is mediated in part by the vagus and in part by a vagally independent mechanism which may be neural or hormonal. Alternatively, vagal noncholinergic inhibition is a major mechanism modulating the motilin response after oral food but motilin release exclusively from intestinal nutriments is mediated by nonvagal, noncholinergic mechanisms.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4028912 TI - Diagnostic and prognostic implications of plasma amino acid determinations in chronic active hepatitis. AB - To further assess the molar ratio of branched-chain to aromatic amino acids as a measure of disease activity, we correlated results of this test with histologic features of inflammation, standard biochemical tests, and prognosis in 68 patients with severe chronic active hepatitis. An abnormal molar ratio (less than 3.0) reflected histologic findings of chronic active hepatitis in 26 of 35 instances. A normal molar ratio (greater than or equal to 3.0), however, was associated with histologic features of chronic active hepatitis in nine of 14 instances. Molar ratio abnormalities occurred more frequently in patients with cirrhosis than without cirrhosis (95% vs 45%, P less than 0.01). Only one of 20 patients with cirrhosis had a normal ratio, and none of 12 followed serially during therapy improved the ratio to normal. No correlation was seen between the molar ratio and severity of inflammation or serum levels of aspartate aminotransferase, albumin, bilirubin, and gamma globulin. When corticosteroids were discontinued, relapse occurred as frequently in patients with a normal molar ratio as in others (80% vs 71%), and the presence of an abnormal ratio did not preclude a sustained remission after treatment. We conclude that the plasma molar ratio does not reflect histologic activity, correlate with standard liver function tests, or indicate disease behavior after treatment withdrawal. A normal molar ratio during or after treatment, however, may exclude cirrhosis. PMID- 4028913 TI - Low blood selenium levels in alcoholics with and without advanced liver disease. Correlations with clinical and nutritional status. AB - Selenium deficiency has been implicated as a cause of hepatic injury, possibly from accentuated lipoperoxidation due to decreased activity of the selenoenzyme, glutathione peroxidase. Because of possible clinical and biochemical links between selenium and alcohol, we performed nutritional assessment and assayed red blood cell, plasma, and whole blood selenium by spectrofluorometry in 27 normals (group I), 30 asymptomatic alcoholics on admission to a detoxification unit, (group II) and 16 alcoholics with severe liver disease (group III). We found a mean (+/- SD) whole blood selenium of 0.109 micrograms/ml +/- 0.014 for group I vs 0.076 +/- 0.010 for group II (P less than 0.001), and 0.047 +/- 0.006 for group III (P less than 0.001 vs group I and II). For plasma, the mean (+/- SD) selenium was 0.095 micrograms/ml +/- 0.016 for group I versus 0.065 micrograms/ml +/- 0.012 in group II and 0.038 micrograms/ml +/- 0.007 in group III (All P less than 0.001). Calculated red blood selenium levels were also significantly reduced in alcoholics versus controls. Whole blood and plasma selenium correlated directly with serum albumin. For whole blood selenium versus albumin, r = 0.73 (P less than 0.01), and for plasma selenium versus albumin, r = 0.71 (P less than 0.01). A significant inverse correlation was noted between whole blood selenium and the height of the total serum bilirubin (r = -0.46), alkaline phosphatase (r = -0.50), and AST (r = -0.51) (P less than 0.01 for all). Among alcoholics admitted for detoxification, selenium was diminished despite the absence of severe malnutrition, as determined by standard nutrition assessment parameters.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4028915 TI - Intradiaphragmatic abscess. An extremely rare complication of pneumatic dilatation of the esophagus. AB - A patient with dysphagia initially diagnosed as achalasia but now thought to have spinocerebellar degeneration manifesting itself in the esophagus as achalasia, developed an intradiaphragmatic abscess, presumably as a complication of pneumatic dilation of the esophagus. This previously unreported complication occurred as a result of transmural spread of bacteria at the time of dilatation with seeding of the diaphragmatic muscle. An intradiaphragmatic abscess may be mistakenly diagnosed clinically and radiologically as a subphrenic abscess or loculated empyema. Management of intradiaphragmatic abscess is discussed briefly. PMID- 4028914 TI - Fecal bile acid excretion pattern in colonic cancer patients. AB - Epidemiological investigations have shown an association between the incidence of colonic cancer, dietary habits, and bile acid metabolism. We analyzed the fecal bile acid excretion pattern in 23 patients with colonic carcinoma and in 21 controls. We determined the total bile acid concentration, the concentration of individual bile acids as a measure for bacterial degradation, and the degree of sulfation. Separation of nonsulfated and sulfated bile acids was achieved by the lipophilic anion-exchanger DEAP-Sephadex-LH 20, quantification of individual bile acids by gas-liquid chromatography. Corresponding with a significantly lower stool mass per day, colonic cancer patients had a lower daily bile acid excretion. But we found no statistically significant difference between the groups in the fecal concentration of total or individual bile acids or their mode of conjugation. There was a wide variation of total bile acid concentration within each group. Most bile acids were expectedly in the free state, only a low percentage in the glycine- or taurine-conjugated form. The sulfated fraction was small and not different in the two groups. Although our data do not refute the hypothesis of bile acids being implicated in the pathogenesis of colorectal cancer, they do not support it. PMID- 4028916 TI - Pancreatic stone protein. PMID- 4028917 TI - Perinatal development of cytochrome P-450, cytochrome C reductase, aryl hydrocarbon hydroxylase, styrene monooxygenase, and styrene epoxide hydrolase in rabbit liver microsomes and nuclei. AB - The development of cytochrome P-450, cytochrome C reductase, aryl hydrocarbon hydroxylase, styrene monooxygenase, and styrene epoxide hydrolase was studied in fresh rabbit liver nuclear and microsomal preparations. Enzymatic activities were determined in rabbit fetus at 21 and 30 days of gestation and in rabbits at 1, 5, 11, 22, 44, and 60 days of age. In extrauterine life, nuclear cytochrome P-450, aryl hydrocarbon hydroxylase, and styrene epoxide hydrolase were found to develop later than their microsomal counterparts, whereas nuclear cytochrome C reductase developed earlier than its microsomal counterpart. The behavior of styrene monooxygenase was more complex. The only activities detectable before birth were styrene epoxide hydrolase, styrene monooxygenase, and cytochrome C reductase in both nuclei and microsomes. The microsomes-to-nuclei epoxide hydrolase activity ratio was almost ten times the microsomes-to-nuclei styrene monooxygenase ratio, indicating a dissociation in the development of the two enzymes in rabbits. Nuclear metabolic activity was high at all ages, suggesting possible toxicological relevance. PMID- 4028918 TI - Oxytocin release induced by melatonin in the ewe. AB - The pineal gland indolamine melatonin now appears to be a primary mediator of the timing of estrus in mammals. Because the neurohypophyseal nonapeptides arginine vasotocin and oxytocin have recently been identified in the pineal glands of several species, we sought to assess the possibility of an interaction between melatonin and the neurohypophyseal hormones. An acute melatonin infusion (216 mumol) was administered to pregnant and nonpregnant ewes. Although plasma arginine vasopressin and arginine vasotocin levels did not change, melatonin produced a significant increase in plasma oxytocin in the nonpregnant though not the pregnant ewe. These data suggest a possible interaction between melatonin and oxytocin in the integration of mammalian reproduction cycles. PMID- 4028919 TI - Severe hyponatremia with indomethacin--a more serious toxicity than previously realized? AB - Five low-birth-weight neonates, ranging from 580 to 1,430 g, developed clinically significant hyponatremia (less than 130 mg/dl) within 48 h after being given indomethacin for patent ductus arteriosus closure. The extent of this hyponatremia is much more severe than previously reported. This group of infants is compared to another group of 5 patients who received indomethacin but did not develop severe hyponatremia. Several possible explanations for the observed differences are explored. PMID- 4028920 TI - Manipulation of sensitivity in visual field investigation. AB - Sophistication of computer software and flexibility of stimulus and background luminance parameters in static perimeter design offer the opportunity for increased information in the assessment of the visual field. Relationships between dynamic ranges and resulting sensitivity gradients in a group of 10 normal 21 year old subjects using the Octopus automated perimeter, the Dicon Autoperimeter 2000 and the Friedmann VFA II are assessed. Inadequacies in the use of normative data to assess the visual field are noted. Implications for the use of dynamic range/sensitivity gradient relationships in visual field assessment without reliance on normative data are discussed. PMID- 4028922 TI - Should visual field examination be a routine part of ophthalmic practice? AB - Visual field screening conducted on indication was compared with routine visual field screening to determine the effectiveness of these strategies in identifying patients with normal and abnormal visual fields. The sample consisted of 1,500 consecutively presenting patients. Each patient was screened with the Friedmann Visual Field Analyser Mark II. Visual field defects were detected in 3.0% of eyes. Routine visual field screening detected a very high proportion of these defects. The two indications approaches which were tested achieved only slightly lower sensitivities and specificities, while necessitating that only approximately 20% of patients required screening. The most effective strategy for screening on indication was based on overall clinical assessment of each case, although the optimal criteria relied on low levels of suspicion. PMID- 4028921 TI - Bilateral oculomotor abnormalities in strabismic amblyopes: evidence for a common central mechanism. AB - The preferred eyes of strabismic amblyopes, generally presumed to be normal, have been implicated by recent studies as manifesting oculomotor abnormalities. We sought to determine whether these motor abnormalities occurred together and, if so, whether they could be related to a single underlying deficit. Occurring together in the preferred eyes of our strabismic amblyopes were: unsteady fixation (consisting of nasal drifts alternating with temporal saccades), minute fixational eccentricity (as indicated by eccentric directionalization of the Maxwell spot) and asymmetries of pursuit tracking. These motor abnormalities of the preferred eye are attributable to the presence of high-velocity nasal drifts. Since nasal drifts also account for several qualitatively similar motor abnormalities exhibited under monocular conditions by the fellow amblyopic eye, we conclude that a centrally-generated nasal drift bias is responsible for anomalous oculomotor behaviors of both eyes of strabismic amblyopes. PMID- 4028923 TI - Informational content of visual field location in glaucoma. AB - Information Theory has been applied to produce estimates of how valuable each stimulus location on the Friedmann Visual Field Analyser mk. II is in detecting early glaucomatous visual field defects. The results indicate that stimuli in the superior arcuate region of the visual field and in the inferior nasal quadrant give the maximum amount of information. Stimuli in the extreme superior field (beyond 20 degrees), the inferior temporal quadrant and around the physiological blind spot give the least amount of information. It is suggested that these results can be used to develop computerised techniques for the analysis of visual field data. PMID- 4028924 TI - Surplus reaction of checkerboard-VEP's. PMID- 4028926 TI - The influence of age on the spatial and temporal contrast sensitivity function. AB - A clinical technique for sampling the spatial and temporal CSF at low, intermediate and high frequencies is described. Reductions in contrast sensitivity with age were shown with the highest spatial and temporal frequency stimuli. The reductions can be almost completely accounted for by the reduction of pupil area with age, causing a reduction in retinal illuminance. The results show a significant deterioration in vision with age that is not revealed by standard visual acuity testing. PMID- 4028927 TI - [Alkaline phosphatase of the cutaneous glands and vessels in the rat and mouse]. PMID- 4028925 TI - The influence of age on the electroretinogram and visual evoked potential. AB - Changes in the ERG and VEP across the life span were investigated. The dark adapted and scotopic ERGs both showed a progressive increase in the implicit times of the A and B waves and a reduction in the amplitude of the AB configuration. There was also an increase in the implicit times of the oscillatory potentials of the photopic ERG. The flash and pattern onset-offset VEP both showed changes in waveform with age whilst the waveform of the pattern reversal VEP was constant. The amplitudes of the components of the flash and pattern reversal VEP were very high in the teenage group, but once reduced, were constant from the twenties onwards, showing no further consistent age changes. The latencies of the components of the pattern VEPs showed an increase with age which could be accounted for by the reduction in retinal illuminance due to the decrease in pupil diameter with age. However, the increase in the latency of the flash major positive (P2) component was greater than that expected from the decrease in retinal illuminance alone, suggesting that this is due to neural factors. PMID- 4028928 TI - [Comparative study of the accumulation of free radicals and DNA breaks during the gamma irradiation of DNA solutions and cells]. PMID- 4028929 TI - [Rhodopsin fluorescence in the retinal rods of the bull at -196 degrees C]. PMID- 4028930 TI - [Conformation of 1,3-bis(p-chlorobenzylidene amino)guanidine (chimcoccide) and its interaction with calcium ions]. PMID- 4028931 TI - [Effect of air bubbles in the human external acoustic meatus on underwater sound perception]. PMID- 4028932 TI - [Compensatory reorganization of the visceral analyzer at the level of the neocortex]. PMID- 4028933 TI - [Ectopic production of hormones and embryonic proteins by stimulated human lymphocytes]. PMID- 4028934 TI - [Action of the volatile components of the urine on the generative function of sexually immature male house mice Mus musculus L]. PMID- 4028935 TI - [Inactivation of the cluster of rRNA genes in the chromosome pair no. 2 in Aleutian minks]. PMID- 4028936 TI - [Limiting phenomena in mutagenesis]. PMID- 4028937 TI - [Specific chemical reaction of 5'-alkylating oligodesoxythymidylate derivative with DNA of human placental chromatin]. PMID- 4028938 TI - [Biosynthesis of pro-opiomelanocortin and secretion of its fragments by cultured bone marrow cells of mice]. PMID- 4028939 TI - [Effect of butylhydroxytoluene on metabolic activation and inactivation of diethylnitrosamine in liver microsomes of rats]. PMID- 4028940 TI - [Does muscle contraction require energy expenditure irrespective of the amount of work?]. PMID- 4028941 TI - [New data on the organization of descending hypothalamic pathways obtained by the method of double retrograde labeling of neurons with fluorochromes]. PMID- 4028943 TI - [Culture density and ion transport across the plasma membrane in transformed cells]. PMID- 4028942 TI - [Relationship between the functional state of the cerebral cortex and changes in PO2 level during electric stimulation]. PMID- 4028944 TI - [Dystrophic and compensatory regenerative processes in the cortical neurons after hypoxia and the transplantation of embryonic nerve tissue in rats]. PMID- 4028945 TI - [Induction of beta- and gamma-states of comuton regulation of oxidative phosphorylation in rat liver mitochondria during the activation of peroxidation of the mitochondrial membrane lipids]. PMID- 4028946 TI - [NMR tomography of experimental malignant neoplasms in vivo]. PMID- 4028947 TI - [Local inhibition in the dendrites of the cerebral cortical neurons]. PMID- 4028948 TI - [Long-lived heterokaryons of animal and yeast cells]. PMID- 4028949 TI - [Absence of point mutation in the 12th codon of the c-Ha-rasl transforming genes of human breast and stomach cancer, melanoma and neuroblastoma]. PMID- 4028950 TI - [3-dimensional organization of the basal plate of phage T4 in the star configuration]. PMID- 4028951 TI - [Keto-enol tautomerism of guanine]. PMID- 4028952 TI - [Fibrillar structures of the cell nucleus and the initial characteristics of their constituent proteins]. PMID- 4028953 TI - [Optimal arteriovenous differential in oxygen concentration during physical loading]. PMID- 4028954 TI - The health benefits of moderate alcohol consumption: a review of the literature. AB - A review of the literature on the positive benefits of light and moderate alcohol consumption suggests the following: Alcoholic beverages are food, containing approx. 7 calories per gram of ethanol. Beer contains small percentages of the recommended daily allowance of vitamins and significant proportions of the recommended daily allowance of trace metals and minerals. Wine, while possessing significantly smaller amounts of vitamins and minerals than beer, has considerably more iron. Both beer and wine have a favorable potassium to sodium ratio. Coronary heart disease (CHD) seems to have a negative association with regular alcoholic beverage use. While some report a linear relationship, most studies agree that the relationship is U-shaped. Many studies have suggested that this inverse relationship is due to alcohol's effect of increasing levels of high density lipoprotein cholesterol (HDL), which acts in the removal of cholesterol from tissue. Other explanations for moderate alcohol's cardioprotective effect include: associated diet changes in moderate drinkers, the silicon content in wine and beer, decreased platelet aggregation and coagulation, and the ability to lessen stress and/or alter personality patterns associated with CHD risks. Dry non-sweet wines and diluted distilled spirits have been recommended in the treatment of diabetes. It has been suggested that alcohol may improve glucose tolerance and blood glucose response to ingested carbohydrates. Due to reported decreased HDL values in diabetics, alcohol has been suggested as useful for its HDL-increasing function. PMID- 4028955 TI - [Traumatic damage of the posterior cranial fossa in chronic alcoholism]. AB - Traumatic damage in the posterior fossa is a relatively rare event. A case of a 52-year-old alcoholic is reported who had two severe head traumas during a fight. The subsequent complaints consisted in vertigo and ataxia and were related to a post-commotional syndrome or damage due to chronic alcoholism. The neurological work-up, which was performed a few months later showed typical signs of traumatic damage of the cerebellum. This was confirmed by axial CT-scan. PMID- 4028956 TI - Alcohol consumption and morbidity in the Canada Health Survey: inter-beverage differences. AB - This study examined inter-beverage differences in the relationship between alcohol consumption and health status as reported by 17 249 respondents to the Canada Health Survey. Self-reported morbidity rates (bed-days, activity loss, doctor visits) were computed for consumers of beer, wine, liquor and for those with no specific beverage preference. These rates were compared with the level of expected morbidity based on each group's demographic attributes. Subsequently, dose-response relationships were described relating frequency and quantity of consumption to a standardized morbidity rate for each beverage-preference group. In general, the results supported the importance of inter-beverage differences as an intervening variable in the relationship of consumption to morbidity. Overall morbidity rates and both frequency and quantity dimensions of the dose-response relationship varied markedly as a function of type of beverage consumed. Beer drinkers, in particular, varied from other consumers they had significantly lower rates of morbidity than expected. Increases in frequency of beer drinking were associated with reductions in morbidity, but mildly deleterious effects were associated with excessive consumption. PMID- 4028957 TI - Coping strategies and relapse in alcohol abuse. AB - This is a study of relapse in problem drinkers and its relation to the employment of techniques for coping with or avoiding tempting situations. A treatment group, consisting of problem drinkers, was instructed in the use of such techniques while another group of drinkers were randomly assigned to a control condition. There was a strong correlation between avoidance of relapse and the use of techniques in both groups but no difference between groups either in relapse or in the use of techniques. There was a tendency for instruction in the use of techniques to be efficient for patients who believed that they could control drinking, but not for others. The treatment seemed to make patients more convinced that it was important to quit drinking. PMID- 4028958 TI - Amoxapine-induced tardive dyskinesia. AB - A case report of amoxapine-induced tardive dyskinesia following discontinuation of amoxapine therapy is reported. During 68 weeks of therapy, the patient received a maximum of amoxapine 400 mg/d. Six months after amoxapine discontinuation, the patient continued to have symptoms of tardive dyskinesia. These symptoms correlate with the dopamine receptor-blocking property of amoxapine and its metabolites. We propose that amoxapine therapy be monitored for the long-term as well as the short-term adverse effects of dopamine receptor blockade. PMID- 4028959 TI - Recurrent dystonic reactions induced by thiethylperazine. AB - Three attacks of acute dystonia occurred in a 19-year-old male following the initiation and discontinuation of thiethylperazine administered rectally in therapeutic doses. The time course of onset of the attacks and the proposed mechanisms by which dystonia develops are discussed. PMID- 4028960 TI - Jaundice associated with cephalosporin therapy. AB - Two cases of cephalosporin-induced hepatotoxicity with associated jaundice are presented. Both patients developed jaundice and liver enzyme abnormalities soon after injectable cephalosporin therapy was started. Other possible causes were ruled out, including TPN and allopurinol hepatoxicity, and additional medical illnesses associated with hepatoxicity. Both patients recovered fully from the episode of jaundice. Review of the literature suggests a possible hypersensitivity reaction similar to liver toxicity of the penicillin antibiotics. PMID- 4028961 TI - A warfarin-piroxicam drug interaction. AB - A piroxicam-warfarin interaction is presented with a discussion of the possible mechanism of action. A 60-year-old white male on warfarin therapy for recurrent pulmonary embolism and deep venous thrombophlebitis showed a decrease in his previously therapeutic and stable prothrombin time when piroxicam was discontinued from his drug regimen. On two rechallenges over a ten-month period, his prothrombin times showed consistent and clinically significant fluctuations as piroxicam was added and deleted from his drug regimen. PMID- 4028962 TI - Verapamil-rifampin interaction. AB - A case of verapamil-rifampin interaction is presented in a patient receiving verapamil for supraventricular tachycardia (SVT) and rifampin for pulmonary tuberculosis. The patient experienced recurrent symptomatic SVT, despite receiving verapamil 480 mg po q6h. Serum verapamil concentrations were determined to be extremely low. Discontinuation of rifampin and substitution of ethambutol resulted in an almost four-fold increase in verapamil levels with concurrent control of SVT. Rifampin may have increased the metabolism of verapamil by inducing hepatic microsomal enzymes resulting in low verapamil levels and failure to control SVT. PMID- 4028963 TI - Subcutaneous epinephrine vs. nebulized metaproterenol in acute asthma. AB - The efficacy and side effects of subcutaneous epinephrine (E) and aerosolized metaproterenol (M) were compared in acute asthma. Adults randomly received E 0.3 mg sub-Q q20min (max 0.9 mg; n = 20) or M 15 mg in 3.0 ml NaCl 0.9% nebulized over 10 minutes (n = 20) in a double-blind fashion. Vital signs and peak expiratory flow rate (PEFR) were measured every ten minutes for one hour. The two groups were comparable in age, weight, baseline theophylline concentration, PEFR, heart rate, and systolic and diastolic blood pressure. PEFR improved in both groups within ten minutes (p less than 0.01; analysis of variance). There was no difference in PEFR between the groups over the one-hour observation period following treatment. Heart rate decreased following treatment in M patients (p less than 0.05), but remained unchanged in E patients. Systolic blood pressure rose slightly in E patients (p less than 0.01), but remained unchanged in M patients. Subcutaneous E and nebulized M are equally effective as initial therapy in acute asthma. PMID- 4028965 TI - Phenytoin once-daily dosing in geriatric patients. PMID- 4028964 TI - Propranolol's effect on phagocytizing ability of polymorphonuclears and monocytes. PMID- 4028967 TI - Professional development degrees. PMID- 4028966 TI - In vitro adsorption of sodium phenytoin by anion exchange resin. PMID- 4028968 TI - Comment: Amphotericin B bladder irrigations. PMID- 4028969 TI - Comment: Ceforanide half-life. PMID- 4028970 TI - Rho Chi Lecture Award. Is it possible to teach scientific creativity in the pharmaceutical sciences? Anecdotes and memorabilia. AB - Finally, and what may be a fitting end for this recounting, there is a quotation of Francis Bacon's that gives a poetic interpretation of creativity in the scientist: "A scientist is neither an 'ant,' storing what it finds lying about ready-made, nor a 'spider,' spinning a web out of what its entrails secrete. He is a bee, visiting innumerable flowers and collecting the nectar it finds in them; but storing not this nectar in its crude state but the honey into which it turns." PMID- 4028971 TI - [Severe skin burns caused by a photochemotherapeutic agent]. AB - By uncontrolled application without indication of a photoactive drug methoxypsoralen (Meladinine) which is sold only on prescription a 20-year-old man sustained a large burn injury of 71% of body surface. Because he was admitted to the hospital relatively late, a life-threatening condition developed as it is well known after large body burns. Adequate intensive care including artificial respiration and proper local treatment to prevent infection were decisive for successful treatment. PMID- 4028972 TI - [Criteria for medical expert opinion under social compensation law and according to the law on the severely disabled]. PMID- 4028973 TI - The influence of low concentrations of irritants on skin barrier function as determined by water vapour loss. AB - The effect of some irritants on the barrier function of the skin was assessed by means of water vapour loss measurements. 100 microliter of the test substance in distilled water were applied to the skin for a period of 48 h, using large Finn chambers. The exposures were done in a test panel of 42 subjects. Sodium lauryl sulfate (2%), cocobetaine (2%), crotonaldehyde (0.75%) with sodium lauryl sulfate (0.5%) and dimethyl sulfoxide (50%) markedly influenced water vapour loss. Sodium hydroxide (1%) had less effect on water vapour loss, although the increase was significant (p less than 0.05). Phenol (5%) and benzalkonium chloride (0.2%) did not significantly influence the loss of water through the skin. It is concluded that subclinical effects of chemicals on the barrier function may be of importance in the development of irritant contact dermatitis, but that this capacity is probably not the only factor which determines the potential of a substance to contribute to the development of irritant contact dermatitis. A chemical which has little or no effect on the function of the horny layer may have a toxic effect on the viable cells of deeper layers of the skin. This toxic effect may also be an important subclinical factor in the development of irritant contact dermatitis. PMID- 4028974 TI - [Multiple bowenoid arsenic keratoses]. AB - Case report of multiple keratoses and chronic lymphatic leukemia after arsenic poisoning 30 years ago during a one-year exposure to copper acetoarsenate in a pesticide factory. Absorption through the skin with local arsenic skin damage is discussed. Etretinate therapy (1 mg/kg b. w.) was ineffective. PMID- 4028975 TI - Selenium deficiency and detoxication functions in the rat: effect of chronic dietary cadmium. AB - Male rats from moderately selenium-deficient dams were fed a Torula yeast-based, selenium-deficient diet for 7 weeks, with or without added supplements of sodium selenite (0.2 ppm selenium) and cadmium chloride (50 ppm cadmium) in the drinking water. Cadmium caused about 10% body-weight loss in selenium-deficient, as well as in supplemented rats. Glutathione peroxidase activity in liver 105,000 g supernatant and in erythrocyte hemolysate from selenium-deficient rats was about 1% and 3%, respectively, of that in supplemented rats. A cadmium-induced decrease of glutathione peroxidase activity was found in erythrocyte and liver preparations from selenium-supplemented rats, while cadmium caused an increase of the liver activity in selenium deficiency. Selenium deficiency per se caused a significant decrease of cytochrome P-450 content, while cadmium treatment did not modify further the content of this enzyme. NADPH-cytochrome c reductase was not changed by selenium regimen or cadmium treatment, while cytochrome b5 was increased on cadmium treatment of the supplemented rat. The microsomal metabolism of N,N-dimethylaniline showed a decrease of the cytochrome P-450-dependent C oxygenation in selenium-deficient groups. Cadmium treatment had no further significant effect. The flavin-containing monooxygenase, which performs N oxygenation of N,N-dimethylaniline, was decreased significantly by cadmium treatment in selenium deficiency. Selenium deficiency seems thus to be connected with higher susceptibility to cadmium-induced impairments of liver detoxication functions, although progressive accumulation of cadmium in the liver appears to produce only modest effects. PMID- 4028976 TI - Effect of gold on selenium and glutathione peroxidase activities in rat tissues. AB - Gold (Au) thioglucose, used to treat inflammatory diseases such as rheumatoid arthritis, inhibits the selenium (Se)-dependent glutathione peroxidase. The present study examines the ability of Au to act either as a Se antagonist or as a GSH peroxidase inhibitor in vivo. The effects of gold thioglucose loading on Se distribution, and on Se-dependent GSH peroxidase and GSH S-transferase, were examined in rats fed three dietary levels of Se (0, 0.2, and 2.0 ppm), and with or without adjuvant-induced inflammation. Kidney, liver, spleen, testes, and erythrocytes were selected for study based upon their high Se content and their ability to concentrate Au. Au loading increased kidney, liver, and spleen Se concentrations, and this effect was dependent upon dietary Se levels. Rats fed Se supplemented diets had higher levels of Au in kidney, liver, and spleens than did rats fed a Se-deficient diet. Au loading decreased GSH peroxidase activity in kidney, liver, and erythrocytes. The decrease in GSH peroxidase in kidney and liver, and the increase in Se concentration in these tissues, suggest that Au-Se complexes may have limited the biosynthesis of the enzyme. Au affects Se distribution, and Se concentrates Au in tissues with a high lysosomal content. PMID- 4028977 TI - [Benzodiazepine: long-term use or abuse? Results of an epidemiologic study)]. AB - Analysis of the prevalence of the diagnosis benzodiazepine-dependence showed that there were only 150 cases (0.5%) out of almost 33 000 admissions during the period 1974 to 1983 and that a noticeable rise in frequency occurred after 1981. In a prospective quarterly incidence study for 1984, 18.5% of patients admitted fulfilled the criteria for long-term users (longer than 3 months continuous administration). PMID- 4028978 TI - [Therapeutic plasma exchange in severe tropical malaria]. AB - Cases of malaria are being seen ever more frequently in the Federal Republic of Germany, presenting both diagnostic and therapeutic problems. Three recent cases of severe malignant falciparum malaria are presented, one ending fatally. In the other two, plasma exchange combined with haemodialysis led to a cure. PMID- 4028979 TI - [Fatal poisoning by the retard form of verapamil. Therapeutic considerations]. AB - A 60-year-old woman swallowed 2.4 g verapamil in a retard form (Isoptin retard). Depsite intensive efforts she died 44 hours later in a coma due to circulatory collapse. In contrast to other reported cases of poisoning, the verapamil concentration in plasma continued to rise. This atypical course with continuing absorption of verapamil was due to small-intestinal deposits of the drug, found at autopsy. PMID- 4028980 TI - [Diagnosis of the pneumonias]. PMID- 4028981 TI - [Extent of the physician's right to withhold testimony]. PMID- 4028982 TI - [Glomerulonephritis associated with nephrotic syndrome in Staphylococcus albus infection in a patient with a Spitz-Holter shunt]. PMID- 4028983 TI - [Fiber bronchoscopy]. PMID- 4028984 TI - [Drug toxicity-induced pulmonary edema]. PMID- 4028985 TI - [Malignant melanomas in pregnancy]. AB - A malignant melanoma was diagnosed and treated during pregnancy in twelve patients average age 29 (19-38) years. Eleven patients were in stage I and one in stage II. One patient presented with 2 primary malignant melanomas. There was no essential difference in localisation or melanoma type in comparison with non pregnant melanoma patients. From histological criteria (tumor thickness and prognostic index) eight patients in stage I had an intermediate and three a high risk of metastases. When compared with non-pregnant melanoma patients the pregnant patients presented with relatively more melanomas having intermediate and high metastases risk. No prediction as to the course of the disease can be made because of the small number of patients. Published data show, however, that in a pregnant subgroup pregnancy has a negative influence on the course of malignant melanoma. PMID- 4028986 TI - [Pregnancy after malignant melanoma. A follow-up of 23 patients]. AB - There is little known on the risks associated with pregnancy occurring after primary therapy of a malignant melanoma. Out of a total of 2850 melanoma patients there were 23 women (20 in stage I, 3 in stage II) in whom 33 pregnancies occurred in the course of the follow-up. No metastases developed in 18 patients with a total of 25 pregnancies whereas a relapse occurred in 3 patients in stage I and 2 patients in stage II. The induction of metastases by the pregnancy in 3 of these patients is unlikely owing to the absence of a temporal relationship or because of an existing stage II and only in 2 patients did the temporal relationship between spreading of the tumor and pregnancy suggest an influence of pregnancy on malignant melanoma. PMID- 4028988 TI - [Lymph node biopsy in lymphadenopathy syndrome and AIDS]. PMID- 4028987 TI - [Bronchodilator effect of fenoterol aerosol. Are 4 0.1-mg doses better than a single dose of 0.4 mg?]. AB - The bronchodilator effect of a single dose of 0.4 mg fenoterol aerosol was compared with the sequential application of the same total dose in 11 patients with bronchial asthma. The patients received either 0.4 mg fenoterol followed by 3 doses of placebo at 30 minute intervals or four 0.1 mg doses of fenoterol each at 30 minute intervals on 2 days in a double-blind randomised investigation. Both application forms had a marked bronchodilator effect. At 60 minutes two 0.1 mg doses of fenoterol had the same effect as the initial dose of 0.4 mg whereas at 120 minutes the sequential inhalation of 0.1 mg had the most marked bronchodilator effect. CONCLUSION: An improvement in beta 2-sympathomimetic inhalation therapy can be achieved more readily by reducing the dose interval than by raising the total dose. PMID- 4028989 TI - [Gastroscopic monitoring of precanceroses of the stomach]. PMID- 4028990 TI - [Unexpected cerebral side effects of ranitidine]. PMID- 4028991 TI - [Alcohol and type I diabetes mellitus]. PMID- 4028992 TI - [Crohn disease: an allergic reaction to absorbed macro-particles?]. PMID- 4028993 TI - [The clonidine inhibition test: an aid in the diagnosis and postoperative therapeutic control in pheochromocytoma]. AB - A clonidine-suppression test was carried out in 8 patients with arterial hypertension, raised urinary and plasma catecholamine levels and symptoms suggesting the presence of a pheochromocytoma. In 6 of the patients clonidine reduced the plasma catecholamine concentrations and no pathological findings were seen in the abdominal computed tomogram (CT). In 2 patients noradrenaline levels were excessively high and not lowered by clonidine; in one of these patients the plasma adrenaline concentration was also raised and this too could not be reduced with clonidine. A tumor was detectable in both patients using CT, in one case situated in the left adrenal, in the other extra-medullary. On operation both were found to be a pheochromocytoma. Peritoneal and intra-hepatic metastases were discovered during surgery in the case of the extramedullary localized tumor. The clonidine-suppression test was repeated postoperatively in both patients: it was normal in the case of the completely excised, intramedullary situated tumor but still pathological in the other. Thus the clonidine-suppression test is useful in the diagnosis and post-surgical assessment of pheochromocytoma. PMID- 4028994 TI - [Double infection with Yersinia enterocolitica 0:3 and 0:9]. AB - An unusual case of Yersiniosis was observed in a 20-year-old woman. Except for an extraordinarily severe onset the clinical course was not remarkable. But two different strains of Yersinia were repeatedly isolated. While strain serotype 0:9 was demonstrated only transiently and gave an only weak immune reaction, serotype 0:3 persisted longer and stimulated a strong immune reaction. But both strains had similar virulence characteristics in different tests, such as plasmid demonstration, autoagglutination, growth on Ca-deficient agar, and in mice. PMID- 4028995 TI - [Fibrinolytic therapy. Indications and execution]. PMID- 4028996 TI - [Directions for TSH screening of newborn infants]. PMID- 4028997 TI - [Experiences with telemetry-supported pacemaker controls in patients with VVI pacemakers]. AB - Investigations on telemetry-supported pacemaker control were carried out in 55 patients with the VVI-pacemaker Quantum (Intermedics). The investigations were done at least once during the 6-24 month period after implantation. The telemetry function was utilised for pacemaker programming, for clarifying pacemaker defects and for characterising the type of pacemaker electrode used. It could be shown that the Osypka spiral electrode VY (Dr. Osypka) had a lower impedance, and greater pulse width and charge threshold in comparison with the two other electrodes used (Encor, Cordis; Polyflex, Intermedics). In 38 of the 55 patients (69%) a pulse amplitude of 2.7 V could be chosen, whereas an amplitude of 5.4 V was programmed in the rest. Pacemaker sensing threshold was set to values between 2.4 and 3.0 mV. Pacemaker problems appeared in three patients; in one patient due to programming too economically and in the other two due to pacemaker defects. PMID- 4028998 TI - [Rhabdomyolysis. Incidence, causes and diagnosis]. PMID- 4028999 TI - [Diagnosis and therapy of the acral ischemia syndrome]. PMID- 4029000 TI - [The new medical instrument ordinance]. PMID- 4029001 TI - [Seroconversion after hepatitis B vaccination by intragluteal or upper arm injection]. PMID- 4029002 TI - [Gastrectomy in microcarcinoidosis]. PMID- 4029003 TI - [The 1985 preclinical examination scandal. Important notes on the preclinical examinations in the spring of 1985]. PMID- 4029004 TI - [Long-term prognosis of acute transmural myocardial infarct after intracoronary thrombolysis treatment]. AB - Reperfusion of the infarct vessel by a combination of intravenous and intracoronary infusion of streptokinase succeeded in 66 of 120 patients with acute transmural infarction in whom the infusion had been started less than six hours after onset of symptoms. The recanalization attempt failed in 26, and 28 were treated conventionally. Size of the infarct was determined by 201Thallium scanning before and 48 hours after the acute treatment phase. Cox analysis indicated that successful recanalization had a significantly positive effect on the long-term prognosis compared with failed thrombolysis or conventional measures. The perfusion defect (as measured by 201Thallium scan) was identical in all three groups, but after successful recanalization with streptokinase it was significantly smaller than in the other two groups. The improved long-term prognosis is presumably due to a decrease in the size of the infarct. PMID- 4029005 TI - [Therapeutic problems in acromegaly]. PMID- 4029006 TI - [Diagnosis of progressive paralysis]. PMID- 4029007 TI - [Ulcer therapy without acid inhibition]. PMID- 4029008 TI - First International Workshop on Temocillin. Proceedings of a symposium sponsored by Beecham Pharmaceuticals held in Athens on 20 September, 1984. PMID- 4029009 TI - In vitro activity of temocillin against clinical isolates. AB - The minimum inhibitory concentrations of temocillin against more than 1000 clinical isolates were determined by an agar dilution method. Temocillin showed excellent activity against Haemophilus influenzae, pathogenic Neisseria species and Branhamella catarrhalis, including beta-lactamase producing strains, but showed very low activity or was inactive against Gram-positive cocci and Campylobacter, Bacteroides, Acinetobacter and Pseudomonas species. Good activity was obtained against 702 Enterobacteriaceae, including isolates resistant to the other penicillins and first- and second-generation cephalosporins, with 92% of all the strains inhibited at a concentration of 8 mg/L. However, the most striking property of temocillin was its high beta-lactamase stability which resulted in both a very narrow range of MICs within which all the isolates were inhibited, and a small influence of inoculum size on the MICs. PMID- 4029010 TI - Temocillin. Summary of safety studies. AB - Temocillin is a novel injectable beta-lactam antibiotic designed for parenteral use. It is active against the majority of Gram-negative bacteria and is stable to a wide range of beta-lactamases. Disposition and metabolic studies on temocillin in animals and man demonstrate that the drug is well distributed throughout the body tissues and will cross the placenta. The major route of elimination is via the kidney (89%) where the drug is excreted unchanged as parent compound, mainly by the glomerular filtration of unbound temocillin. A full toxicological safety evaluation programme has been completed and includes acute, subacute and chronic toxicology in rat and dog, and reproductive and mutagenicity studies. Temocillin was well tolerated in animals at dosages of up to 1000 mg/kg and appears to be without any potential hazard for man in dosages which are well in excess of the proposed therapeutic dose. PMID- 4029011 TI - Pharmacokinetics and tissue penetration of temocillin. AB - The pharmacokinetics of intravenous (bolus) temocillin 1 g were studied in 6 healthy male volunteers, and a cantharides blister method was used to estimate tissue penetration of the antibiotic. The mean elimination half-life was 4.5 hours. Temocillin penetrated blister fluid rapidly and reached concentrations of about 50% of those in serum by 2 to 3 hours after administration. Over an 8-hour period, the serum and blister fluid concentrations exceeded the MIC90 of susceptible bacteria by 2-fold or greater, suggesting that twice or even once daily dosing with temocillin may be sufficient. PMID- 4029013 TI - Temocillin penetration of peripheral lymph. AB - An intravenous dose of temocillin 1g was administered to 5 healthy human volunteers from whom peripheral lymph, serum and urine were monitored for 12 hours. The concentrations after 1 hour were 14.3 mg/L in lymph and 58.1 mg/L in serum. The mean peak concentration in lymph (appearing between 1.5 and 2 hours) was 30.6 mg/L, and the simultaneous serum level was 47.8 mg/L. The lymph concentrations were always below those in serum, and the elimination half-life was 4.4 hours from lymph compared with 4.9 hours from serum. The ratio between the total areas under the concentration curves in lymph and in serum was 0.56, which reflects the ability of temocillin to penetrate to lymph. Serum protein binding appeared to impede the rate of transport from serum to lymph, but when compared with the results of less highly bound penicillins the total penetration of temocillin was better than expected. PMID- 4029012 TI - Effect of renal function and dialysis on temocillin pharmacokinetics. AB - Temocillin pharmacokinetics in renal impairment were investigated following an intravenous bolus injection of 15 mg/kg. The 28 patients were divided into 5 groups of varying renal function, from normal to uraemic [including a group being treated with haemodialysis and a group on continuous ambulatory peritoneal dialysis (CAPD)]. The distribution of temocillin into the tissues was not affected by renal dysfunction. Uraemia as compared to normal renal function resulted in a 4.3-fold decrease in temocillin clearance and a 3.1-fold decrease in urinary recovery over 24 hours, as well as a 5- and 3.7-fold increase in the beta half-life and the area under the curve (AUC), respectively. Haemodialysis doubled the serum clearance and halved the beta half-life of temocillin in the uraemic subject, but CAPD over 24 hours eliminated only 8% of the temocillin dose, resulting in a minimal change in pharmacokinetics. Temocillin dosage adjustments in renal failure are proposed. PMID- 4029014 TI - Clinical efficacy, tolerance and pharmacokinetics of temocillin in patients with respiratory tract infections. AB - In this study 13 patients with a history of chronic respiratory disease were treated with temocillin for severe infection of the lower respiratory tract. Eleven patients were clinically improved or cured at the end of treatment and 4 remained free of infection at follow up. However, the 2 remaining patients failed to respond clinically and bacteriologically to temocillin. Blood and sputum pharmacokinetics were studied in patients receiving temocillin at 12-hourly intervals in doses of either 1g by intravenous bolus or 2g by intravenous infusion. On the first day of treatment the mean peak serum concentration was 102 mg/L for the 1g dose and 220 mg/L for the 2g dose, falling to 11 mg/L (1g) and 18.8 mg/L (2g) at 12 hours. Similar results were recorded on the last day of treatment. Temocillin concentrations in the sputum ranged from 1.5 to 2.8 mg/L, with no difference being found in the sputum concentrations of the 2 doses. Temocillin was well tolerated and was found to be an effective treatment for Gram negative bacterial infections of the lower respiratory tract. PMID- 4029015 TI - Biliary concentrations of temocillin. AB - Serum and bile concentrations of temocillin were measured after intravenous administration of 1g twice daily to 16 patients with biliary tract infections. The concentration of temocillin in the bile showed high inter-individual variations; however, in patients drug concentrations were attained which were considerably higher than the minimum inhibitory concentrations of the biliary tract pathogens identified throughout the study period. All the patients admitted to the study were treated successfully by temocillin, with the tolerance of the drug being very good, and no side effects or drug-related deteriorations of laboratory data being reported. PMID- 4029016 TI - Renal clearance of temocillin in volunteers. AB - After administration of a loading dose, temocillin was infused intravenously into 5 volunteers for 3 hours (250 and 750 mg/h). A urine flow of more than 500 ml/h was maintained. The mean plasma concentrations were 131.4 and 220.7 mg/L during the lower dose and higher dose infusions, respectively, and protein binding decreased from 83% to 74% with this increase in plasma concentration. The renal clearance of the total drug increased from 29.0 ml/min (low dose) to 50.5 ml/min (high dose) [p less than 0.001], but after correction for protein binding the renal clearance of the unbound drug only increased from 169.1 to 197.0 ml/min (not statistically significant). The extrarenal clearance of temocillin was negligible. Blocking of tubular excretion by probenecid caused a maximum decrease of the renal clearance of temocillin from 34.1 to 22.4 ml/min. This maximum effect of 12.3 ml/min subsided by 1.7 ml/min/h. The renal clearance of the free drug decreased to 134.6 ml/min, slightly less than the creatinine clearance (158.1 ml/min). It may be concluded that even at high plasma concentrations of temocillin there is no saturation of the tubular transport mechanism, and that tubular excretion plays a relatively minor role in the renal excretion of the drug. PMID- 4029017 TI - Temocillin pharmacokinetics in normal and impaired renal function. AB - In 18 healthy volunteers and 18 patients with varying degrees of impaired renal function, the plasma concentrations after intravenous administration of temocillin 0.5, 1, and 2g were determined. Another group of 6 patients received temocillin 0.5 g intramuscularly. Surprisingly, it was found that with higher doses, the plasma concentrations, and consequently the area under the plasma concentration/time curve (AUC), did not increase proportionately. Instead, the renal and, to a greater extent, the total clearance of temocillin increased. The plasma concentrations in patients with impaired renal function were clearly higher than in the subjects with normal renal function. Dose-reduction factors were derived which allowed the determination of the dosing regimen necessary to achieve approximately the same high plasma concentrations (and the same AUCs) in patients with impaired renal function as in healthy subjects. However, these dose reduction factors could only be determined for certain doses because of the specific behaviour of temocillin. PMID- 4029018 TI - Biliary concentrations of temocillin. AB - Temocillin is a new semisynthetic beta-lactam antibiotic with a spectrum of activity against most aerobic Gram-negative bacteria. We investigated the biliary excretion of temocillin after administration of 1g either intravenously or intramuscularly to 15 patients with normal liver and renal function who were undergoing elective cholecystectomy for gallstones. Very high concentrations of temocillin (up to 8 times the corresponding serum concentrations) were found in common bile duct bile and gallbladder bile of functioning gallbladders 1 to 2 hours after administration. However, no temocillin was detected in the bile of non-functioning gallbladders. Concentrations of temocillin were significantly higher in common bile duct bile (p less than 0.01) and gallbladder bile (p less than 0.05) following intravenous administration, and there was also a significant correlation (p less than 0.05) between common bile duct bile and corresponding serum concentrations for both routes of administration. Temocillin 1g readily achieved therapeutic concentrations in bile, and may prove a useful agent in the prophylaxis and management of Gram-negative biliary infections. PMID- 4029019 TI - Quantification of temocillin biliary excretion and gallbladder bile concentration in healthy subjects. AB - The techniques of duodenal perfusion with polyethylene glycol as a nonabsorbable marker, and cholescintiscan using 99Tc HIDA as a gallbladder bile marker, were used to measure the total duodenal output and gallbladder bile concentration of temocillin after administration of an intravenous bolus injection to each of 6 healthy subjects. We carried out 8 studies. 3 with 0.5g temocillin and 5 with 1g temocillin. The plasma half-life of temocillin was 177 (+/- 25) minutes [mean (+/ SD)] and 196 (+/- 29) minutes with the 0.5g and 1g doses, respectively. Urinary excretion accounted for 38% of the total dose given during the study period of 6 hours, and total biliary excretion was recorded as 2.2% of the given dose for both doses. The mean concentration of temocillin in gallbladder bile was 314.7 (+/- 273.2) mg/L after the 0.5g dose and 474.5 (+/- 307.3) mg/L after 1g dose. It was concluded that temocillin is highly concentrated in the normal gallbladder in man. PMID- 4029020 TI - Lung tissue penetration of temocillin. AB - Eight patients about to have the whole or part of a lung resected were given a 2g bolus dose of temocillin. A series of serum samples and a piece of peripheral lung tissue were collected and assayed for temocillin concentration. 30 minutes after drug administration, the mean serum and tissue concentrations were 172 mg/L and 45 mg/kg respectively. PMID- 4029021 TI - Human pharmacokinetics and antimicrobial activities of the temocillin epimers. AB - The pharmacokinetics of the epimers of temocillin were investigated in 4 healthy male subjects following intravenous administration of 1g of temocillin disodium (free acid) which contains a R : S epimer ratio of approximately 65 : 35. The R epimer had a 2-fold greater total plasma clearance, a 23% larger volume of distribution and a shorter beta half-life than the S epimer. Intermediate values were obtained for total temocillin (R + S) from high pressure liquid chromatography (HPLC) data. In each plasma sample, the unbound fraction of the R epimer was generally 2-fold higher than that of the S epimer, which is suggested as the reason for the differences in the pharmacokinetic properties of the epimers. The temocillin pharmacokinetic parameters obtained from the microbiological assay data reflect most closely those for the R epimer derived from HPLC data. The resolved R epimer exhibited twice the potency of the S epimer against the microbiological assay organism Pseudomonas aeruginosa NCTC 10701. However, in tests for antibacterial susceptibility, for instance minimum inhibitory concentration (MIC) determinations involving prolonged incubation, there was little difference in the inhibitory activities of the resolved R and S epimers compared with temocillin (R + S), presumably as a consequence of the epimerization of the individual epimers. In contrast, in rapid tests for bactericidal activity, which minimise the effect of epimerization, the R epimer exhibited greater bactericidal activity than the S epimer. PMID- 4029022 TI - A study of the penetration of temocillin in the cerebrospinal fluid. AB - Temocillin concentrations in serum and cerebrospinal fluid (CSF) samples from 8 patients were assayed by high pressure liquid chromatography. It was possible to determine sequential series of ventricular (CSF) and serum concentrations in 4 adult neurosurgical patients with slight to moderate impairment of blood-CSF barriers, because serial CSF samples were obtained from external ventricular drains. In 4 other patients with meningitis, temocillin was given in addition to the regular treatment schedule and 6 'spot' concentrations of temocillin in lumbar CSF and serum samples were determined. Temocillin CSF concentrations in these subjects seemed to be inadequate for the treatment of Gram-positive bacterial meningitis and only partially valuable for the treatment of Gram negative bacillary meningitis. PMID- 4029023 TI - The treatment of complicated and uncomplicated urinary tract infections with temocillin. AB - Temocillin was given to 33 patients with urinary tract infection as a once daily dosage regimen of 500mg intramuscularly or Ig intravenously for 7 to 10 days. The lower dose produced a clinical cure in 83% of patients with uncomplicated infection but was ineffective in complicated cases, whereas the higher dose cured 100% of uncomplicated and 70% of complicated cases and there were no side effects or toxicity. In vitro studies with 120 consecutive clinical isolates of Enterobacteriaceae gave an MIC90 of 8 mg/L for Escherichia coli, although some resistant strains were found in other species. PMID- 4029024 TI - Potential role of temocillin in the treatment of biliary sepsis. AB - Temocillin concentrations were determined in the gallbladder bile and/or common bile duct bile obtained intraoperatively from 20 patients, and in the T-tube bile of 5 postoperative patients. Blood samples were also obtained for determining the concomitant serum antibiotic concentrations. In 6 patients with cholelithiasis, but without common bile duct obstruction or acute infection, the mean temocillin concentrations were 890 mg/L in gallbladder bile and 1030 mg/L in common bile duct bile. In the group of 6 patients with common bile duct obstruction, the antibiotic concentrations ranged between 5.6 and 88 mg/L (mean 38.8 mg/L) in gallbladder bile and between 'undetectable' and 700 mg/L in common bile duct bile. In patients with biliary sepsis, a further reduction in temocillin bile concentrations was observed, and postoperatively, the T-tube bile temocillin concentrations were in the range of 21 to 460 mg/L (mean 130 mg/L). The clinical efficacy of temocillin in the 7 patients with acute cholecystitis was judged to be satisfactory. Our results suggest that temocillin may be considered as a potentially useful antibiotic in the treatment of patients with biliary tract sepsis caused by susceptible organisms. PMID- 4029025 TI - Temocillin in the treatment of chest infections. AB - In our study, 16 patients with acute infection complicating severe respiratory disease were treated with temocillin 2g or 3g daily for 5 to 10 days. In 10 patients, a recognised respiratory pathogen, either Haemophilus influenzae (temocillin-sensitive) or Streptococcus pneumoniae (temocillin-resistant), was isolated from sputum before the start of treatment. 13 patients improved clinically but 5 subsequently relapsed. Two patients failed to respond, and 1 died of respiratory failure. There was no clearcut relationship between the clinical progress and sensitivity of the isolated pathogen to temocillin, and there were no adverse effects associated with the administration of temocillin. PMID- 4029026 TI - Treatment of severe infections with temocillin. Clinical and bacteriological evaluation. AB - Included in a study of the clinical efficacy of temocillin were 20 hospitalised female patients suffering from infections of the respiratory or urinary tract, septicaemia or an abscess. Clinical evaluation revealed fully effective treatment in all patients, and all pathogens identified were eliminated during therapy with no adverse reactions being observed. PMID- 4029027 TI - Single dose therapy with temocillin in acute gonorrhoea. AB - Temocillin has pronounced in vitro activity against both penicillin-sensitive and penicillinase-producing gonococci. A single intramuscular injection of temocillin 0.5 g or 1.0 g resulted in the disappearance of the infecting gonococci in 91% of 75 patients and 94% of 192 patients in 2 separate trials. The systemic and local tolerance of the drug was unusually favourable and no serious side effects were observed. PMID- 4029028 TI - Therapeutic results and tissue concentrations of temocillin in surgical patients. AB - Temocillin, a new beta-lactamase-stable penicillin, was administered in a dosage of 2g twice daily to 25 biliary surgery patients in whom potential septic complications were a concern. Clinical efficacy was assessed as 'very good' in 23 patients. In one patient there was a disorder of wound healing and in another a staphylococcal bronchial pneumonia developed postoperatively. Temocillin was tolerated very well, and no side effects were observed. 12 hours after administration of temocillin 2g intravenously to surgical patients the mean serum concentration was 22.44 (+/- 10.26) mg/L. The median half-life was 3.86 hours (+/ 1.84) hours. Mean concentrations of 12.44 and 38.59 mg/L were measured up to the twelfth hour in the wound secretions and peritoneal secretions, respectively. In skin, fat, fascia, muscle and gallbladder wall, temocillin concentrations greater than the inhibitory concentrations of most Gram-negative bacteria were demonstrated after 1 and 2 hours. PMID- 4029029 TI - Comparative in vitro activity of temocillin. AB - The antibacterial activity of temocillin, a novel beta-lactam antibiotic, was tested against 796 clinical isolates. We also conducted a comparative study against 8 other antibiotics. Temocillin exhibited good activity against Gram negative organisms including Escherichia coli, and the genera Proteus, Enterobacter, Serratia, Klebsiella, Citrobacter, Providencia, Salmonella, Shigella and Haemophilus: 98% of the strains were inhibited by concentrations less than or equal to 16 mg/L. The results of this in vitro study and temocillin's favourable pharmacokinetic properties suggest that temocillin is a very promising penicillin for the treatment of hospital infections caused by Gram negative organisms. PMID- 4029030 TI - Studies with temocillin in the hamster model of antibiotic-associated colitis. AB - The studies reported here were designed to ascertain whether or not the new beta lactam antibiotic, temocillin, would produce antibiotic-associated colitis in the hamster. The experiments were controlled with clindamycin and cefoxitin, which are known to induce antibiotic-associated colitis experimentally and clinically. All three antibiotics were administered to groups of animals both parenterally and orally. Clindamycin, at 1 mg/hamster, caused a slow onset of antibiotic associated colitis by both routes, with death occurring at between 4 and 8 days. 80 to 100% of the animals had diarrhoea and showed signs of haemorrhage and caecal distension, with the caecal contents being Clostridium difficile toxin positive. The onset of antibiotic-associated colitis after administration of cefoxitin was less marked at the 1 mg parenteral dose, with only 40% of the hamsters showing signs of colitis. At the higher doses of cefoxitin, colitis was more severe and the animals exhibited dramatic weight loss, with death occurring at between 3 and 5 days. The majority of animals had diarrhoea and were C. difficile toxin-positive; 60 to 80% also showed signs of haemorrhage and caecal distension. In contrast, the hamsters receiving temocillin remained healthy with no signs of diarrhoea, and showed consistent weight gain. No pathological abnormalities were observed and the caecal contents were toxin-negative. These results suggest that temocillin therapy in humans is unlikely to cause significant disturbance of the gastrointestinal flora. PMID- 4029031 TI - In vitro combination-effect of temocillin with ticarcillin and aminoglycosides on gram-negative and gram-positive bacteria. AB - The in vitro efficacy of temocillin in combination with ticarcillin and with gentamicin, tobramycin, amikacin and netilmicin against 80 Gram-negative and 20 Gram-positive bacterial strains was compared by use of the checkerboard agar dilution technique. No synergistic or additive effect was seen on the Gram positive strains. Great variations occurred between the different bacterial species, and the temocillin-ticarcillin combination had only little effect against the Pseudomonas strains tested. On average, only 12% of all strains tested were inhibited synergistically by temocillin-gentamicin combinations, and only 7 to 10% by combinations of temocillin with the other aminoglycosides. However, 25% of Gram-negative strains were inhibited synergistically and 40% of Gram-negative strains were inhibited additively by the combination of temocillin gentamicin. PMID- 4029032 TI - Pharmacokinetics of temocillin in volunteers. AB - The pharmacokinetics of temocillin, a new semisynthetic parenteral penicillin, were studied in 10 healthy volunteers. Doses of 0.5, 1.0, and 2.0 g were administered by intravenous bolus injection at weekly intervals, and serum and urine samples were assayed by an agar diffusion method. Mean peak serum concentrations were: 77.9 (+/- 28.4) mg/L (0.5 g), 160.8 (+/- 58.2) mg/L (1.0 g), and 236.1 (+/- 93.3) mg/L (2.0 g), with serum concentrations still being measurable after 12 hours for all doses [7.9 (+/- 3.7) mg/L, 12.9 (+/- 5.2) mg/L, 14.8 (+/- 6.3) mg/L]. According to a 2-compartment open model, the mean terminal half-lives of 0.5, 1.0, and 2.0 g doses were 5.2 (+/- 0.3), 5.0 (+/- 0.2), and 5.0 (+/- 0.2) hours, respectively. The total volume of distribution averaged 0.15 (+/- 0.01), 0.17 (+/- 0.01), and 0.24 (+/- 0.01) L/kg bodyweight, respectively, mean renal clearances were 18.5 (+/- 3.2), 19.6 (+/- 5.0), and 29.8 (+/- 2.6) ml/min, respectively, and the area under the serum concentration time curve (AUC) was 344.1 (+/- 18.7), 573.3 (+/- 27.8), and 784.5 (+/- 47.1) mg X h/L, respectively. At 74 (+/- 12.9)%, the 24-hour urinary recovery was highest for the low dose, followed by 68.1 (+/- 6)% for the 2.0 g dose, and 66.1 (+/- 16.8)% for the 1.0 dose. No untoward side effects were recorded. Thus, temocillin appears to be a penicillin with a prolonged half-life and high AUC. PMID- 4029033 TI - Leukotrienes in disease. Implications for drug development. PMID- 4029034 TI - Compliance and the doctor-patient relationship. PMID- 4029035 TI - Glial-neuronal relationship in the developing central nervous system. A histochemical-electron microscope study of radial glial cell particulate glycogen in normal and reeler mice and the human fetus. AB - Glial populations in the developing central nervous system can be recognized at the ultrastructural level by its glycogen content stained selectively by reduced osmium and periodic acid-thiocarbohydrazide-silver proteinate. This method permits the description of glial defasciculation during corticogenesis in the normal mouse and demonstrates a disturbance of this process in the reeler mouse. Combined use of autoradiography and glycogen labeling yields insights into the relationships between migrating neurons and radial glial fibers. This method can also be used to recognize and describe glial fibers in the human fetal brain. PMID- 4029036 TI - Serum-free aggregate cultures of rat CNS glial cells: biochemical, immunocytochemical and morphological characterization. AB - Aggregate cultures of mixed glial cells, as well as of enriched astrocytes and oligodendrocytes were prepared, and maintained in serum-free medium for up to 25 days. Biochemical measurements of both neuron-specific and glia-specific enzyme activities showed that these three types of aggregate cultures were virtually devoid of neurons. Astrocyte-enriched cultures were greater than 95% pure, with oligodendrocytes as the only apparent contaminant, whereas oligodendrocyte enriched cultures still contained a considerable proportion of astrocytes. In all these neuron-free aggregate cultures both astrocytes and oligodendrocytes attained a high degree of maturation. These findings were confirmed by morphological examinations, and by immunofluorescence studies. Furthermore, ultrastructural as well as immunocytochemical investigations using antibodies to myelin basic protein revealed that all three types of glial cell aggregate cultures contained myelin membranes, indicating that the presence of axons is not a prerequisite for the formation of myelin. PMID- 4029037 TI - Developmental disturbances in the hamster retina caused by a mutant of mumps virus. AB - Newborn hamsters were inoculated intracerebrally with either the neurovirulent Kilham strain of mumps virus or a mutant (M13) strain of this virus. The M13 strain has an alteration in the haemagglutinin-neuraminidase protein of its envelope and causes a low-grade infection of the brain. Both strains spread consistently to the retina where the Kilham strain caused an extensive necrotizing infection. In contrast, the M13 strain predominantly caused an infection of the retinal pigment epithelium (RPE) with the involvement of scattered neurons in the retina. Only minimal degenerative or inflammatory changes were seen, but at 12 days of age developmental alterations were seen in all eyes. These included stretches with failure of photoreceptor segment development and the formation of folds in the outer nuclear layer. The former changes occurred in areas with loss of RPE cells and the latter generally in connection with displaced pigment-loaded cells from the RPE layer. It is suggested that these retinal alterations are mainly secondary to the RPE infection with the M13 strain. PMID- 4029039 TI - [Determination of bacterial drug sensitivity]. PMID- 4029038 TI - [Nucleic acid hybridization--an adjunct to microbiological diagnosis]. PMID- 4029040 TI - [Throat cultures in the health center]. PMID- 4029041 TI - [Reye's syndrome--visceral fatty degeneration and encephalopathy]. PMID- 4029042 TI - [Right ventricular infarction--a treatable form of cardiogenic shock]. PMID- 4029043 TI - [The benefits of total hip replacement]. PMID- 4029044 TI - [Hepatitis A epidemic in an infant day care center]. PMID- 4029045 TI - [Serum thyroxine and thyrotropin in the elderly]. PMID- 4029046 TI - [Hyperparathyroidism and large parathyroid cyst]. PMID- 4029047 TI - [Rat-bite fever]. PMID- 4029048 TI - [Deaths resulting from yellow jacket and bee stings in Finland]. PMID- 4029049 TI - [Clinicopathological conference. A patient with hiccups]. PMID- 4029050 TI - Development of sucking rhythm in preterm infants. AB - We studied the ontogeny and temporal organization of non-nutritive sucking during active sleep in 6 healthy preterm infants (mean birthweight 1.1 kg (range 0.8-1.3 kg) gestational age 28.6 weeks (range 26-30 w] from 30 to 35 weeks of post menstrual (PM) age. Recognizable rhythmical sucking bursts were recorded at 28 weeks in one infant and by 31-33 weeks in the others. Results were analyzed for the periods 30-31, 32-33 and 34-35 PM weeks. The number of bursts/min increased with age, while the duration of each burst was stable (mean 4.1 s). The pause between bursts decreased. Sucking pace within bursts increased with age which resulted in an increase in the overall rate of sucking. The coefficient of variation (CV) for intersuck time within bursts and for interburst time was computed to examine the stability of the sucking rhythm. For intersuck time the CV was relatively low and constant across ages. However, for interburst time CV was relatively large across ages. Thus, there appears to be a stability of the intraburst sucking rhythm from 30 weeks of gestation, whereas the interburst rhythm is less regular. This documentation of temporal organization in sucking from 30 weeks is one of the earliest indications of an intrinsic rhythm in human behavior. PMID- 4029051 TI - Influence of social background on psychomotor development in the first year of life and its correlation with later intellectual capacity: a prospective cohort study. AB - The effect of the sex of the child, somatic growth and five family background variables upon psychomotor development during the first year of life was studied by regression analysis in a Northern Finland birth cohort (n = 12 058) for 1966. Children with mental retardation and cerebral palsy were excluded from the series. The significant explanatory variables for the age of learning to stand and to walk without support were gestational age, birth weight, sex and maternal age. The girls and children of young mothers revealed a faster pattern of development. Urban residence enhanced learning to walk with support, an ability which was attained at the same age in both sexes. Female sex was the most powerful explanatory variable for early development of speech, the other significant variable being height at one year, birth weight, low parity of the mother and urban place of the residence. The social class and marital status of the mother proved insignificant for the developmental milestones studied here. The fast learners during their first year of life were superior to the others in their educational capacity at the age of 14 years. The prognosis in this respect was independent of social class. PMID- 4029052 TI - Vitamin A and E content of human milk at early stages of lactation. AB - The influence of gestational age and lactational stage on carotene, retinol ester, alpha-tocopherol and gamma-tocopherol content of early human milk was studied. These nutrients were analyzed simultaneously using normal phase high performance liquid chromatography. Serial samples of colostrum and early milk representative of complete early morning expressions were obtained during the first 6 weeks post-partum from mothers giving birth prematurely (PT) and at term (FT). Colostrum carotene content declined significantly during the first week of lactation. There was no apparent gestational age effect on milk carotene levels. The longitudinal pattern of change observed for milk retinol ester and alpha tocopherol content was however, significantly different between PT and FT milk. Retinol ester levels were similar on days 1-2 postpartum reaching a maximal level on days 3-4 postpartum in FT milk. For PT milk the maximum retinol ester concentration occurred on days 6-7 postpartum. Retinol ester content decreased throughout lactation. The rate of decline was more marked for FT milk. The concentration of alpha-tocopherol in colostrum was higher in FT milk. On all subsequent days examined the level of alpha-tocopherol was greater in PT milk. For both FT and PT milk the alpha-tocopherol concentration was higher during the first week of lactation when compared with following weeks. gamma-Tocopherol levels were not influenced by gestational age or lactational stage. Levels of milk vitamin A and E did not appear to correlate with maternal intake. Colostrum levels of vitamin A and E may imply active sequestration by the mammary gland in compensation for limited placental transport. Early milk content of vitamin A and E appears to parallel mammary gland lipid synthesis. PMID- 4029053 TI - Anthropometric assessment of nutritional status in newborn infants. Discriminative value of mid arm circumference and of skinfold thickness. AB - 74 appropriate-for-gestational age (AGA) and 22 small-for-gestational age (SGA) caucasian infants were studied for anthropometric parameters: mid arm circumference (MAC), triceps and subscapular skinfold thickness (TSKF and SSKF) recorded at 15 and 60 s, chest circumference (cc), head circumference, birth weight and length. MAC is highly correlated with birth weight either in AGA (r = 0.936; P less than 0.001) or in SGA infants (r = 0.860; P less than 0.001). MAC is also correlated with gestational age in AGA (r = 0.850; P less than 0.001) and SGA infants (r = 0.76; P less than 0.001). Similar correlations were found between TSKF, SSKF and birth weight or gestational age. Arm muscle and fat areas are also positively correlated with birth weight and gestational age, in AGA and SGA infants. A multiple regression analysis of our data allowed a classification of the best discriminant anthropometric parameters between AGA and SGA infants. MAC, SSKF15, SSKF60 and chest circumference were selected. An equation was established in AGA infants with these four parameters giving a predictive gestational age: gestational age (weeks) = 1.216 MAC (cm)-3.588 SSKF15 (mm) + 0.263 CC (cm) + 17.9. The ratio of predicted gestational age to the real gestational age was 1.0 +/- 0.044 in AGA versus 0.896 +/- 0.034 in SGA infants. Our data suggest that MAC and SSKF provide a simple measure of body composition of neonates and a useful tool for determining the degree of maturity of a newborn independent of birth weight. PMID- 4029054 TI - Maternal vocalisations and other sounds in the fetal lamb's sound environment. AB - In a first experiment a miniaturised radio hydrophone was implanted inside the amniotic sac in three pregnant ewes and recordings were made from 3 weeks before the lambs were born until they had emerged; these recordings showed that the sound of the mother's voice was slightly louder when picked up by the hydrophone inside the amniotic sac than when picked up by a microphone beside her flank and that sounds recorded during labour included long and loud low frequency sounds associated with contractions, and an increase, compared with before labour, in the incidence of sounds produced by the maternal cardiovascular system and by breathing. Over the last 3 weeks of gestation the attenuation of sounds from outside the mother decreased at frequencies between 500 and 4000 Hz, but not below or above those frequencies. In a second experiment the bleats of 23 pregnant ewes were recorded; their lambs were taken at birth and tested with the sound of either their own mother's bleats, or with bleats from an alien ewe. Heart rate changes which occurred during playback of maternal and alien bleats differed significantly, but only on the occasion when each lamb heard its first bleat, postnatally. PMID- 4029055 TI - Brainstem auditory evoked responses in infants at risk of sudden infant death. AB - Brainstem auditory evoked responses (BAERs) were recorded from 63 near-miss Sudden Infant Death Syndrome (NMSIDS) infants, 26 siblings of SIDS (SSIBS) infants and 67 control infants between 0 and 30 weeks post-term. The majority of BAERs recorded from the NMSIDS and SSIBS infants had normal form and interpeak intervals (V-I and V-IIn) within normal limits for their age. However, 15% of these infants had interpeak intervals outside the normal range, suggesting abnormal neural function in these cases. The distributions of interpeak intervals for all NMSIDS and SSIBS infants were skewed towards longer times compared to control infants. The distributions of V-IIn intervals for both groups of at risk infants were significantly different to that of control infants. While the observations confirm that the recording of BAERs is not suitable for identifying infants at risk of SIDS, they suggest, however, that maturation of neural processing in the brainstem of these infants may be delayed. PMID- 4029056 TI - Effects of aerial applications of cypermethrin and demeton-S-methyl on nontarget arthropods of wheat. AB - Cypermethrin (Ripcord) and demeton-S-methyl (Duratox) were each applied to large fields of winter wheat by fixed-wing aircraft. The numbers of soil surface- and foliar-dwelling arthropods were estimated at intervals before and after treatment in both the treated and an untreated control field, using pitfall traps and a D Vac suction sampler. Cereal aphids were the major group of phytophagous insects collected from all of the trial sites. Both compounds caused an initial decline in their numbers immediately after spraying but a significant "resurgence" in aphid populations was observed in the demeton-S-methyl-treated field towards the end of the study. The major groups of entomophagous arthropods collected from the fields were Carabidae, Staphylinidae, Linyphiidae, Empididae, and Braconidae. With the exception of the effects of cypermethrin on linyphiids and demeton-S methyl on empids, both of the treatments had only minor, short-lived effects on these entomophages. Neither of the compounds had any significant, long-term effects on general feeding (e.g., detritivorous) arthropods. PMID- 4029057 TI - Cellular uptake and subcellular distribution of mercury in chick embryonic retinal cell aggregates. AB - Cellular uptake and subcellular distribution of mercury (203HgCl2) were determined in the chick embryonic retinal cell aggregation system. The accumulation of mercury was dependent upon its concentration in the medium. The uptake was rapid; a maximum deposition of mercury at 5 microM occurred within the first 30 min followed by a decline. Accumulation of mercury at 1 microM was constant between 15 min and 24 hr. The subcellular distribution of mercury was observed in the following order: nuclei and cell debris greater than mitochondria lysosomes greater than 105,000g supernatant greater than microsomes. The activity of acid phosphatase markedly decreased in the aggregates treated with mercury at 50 to 100 microM for 24 hr. Low concentrations of mercury at 0.5 to 5 microM showed an inhibition of this enzyme activity in a cell-free system. The results indicate a relationship between the amount of mercury in the cells and the toxicity it produced on the retinal cell aggregation system. PMID- 4029058 TI - Iron retention and distribution in the cadmium-induced iron deficiency. AB - The retention and distribution of iron-59 after oral administration of a single iron dose in the presence and absence of various cadmium doses were tested in normal rats acutely or subchronically treated with various amounts of dietary cadmium (28, 56, 112 ppm). In a second series of experiments the kinetic parameters (Km and Vmax) of iron absorption were estimated in normal and iron deficient rats after oral administration and from tied-off jejunal and duodenal segments. In acute experiments the retention of iron decreased inversely with respect to the cadmium dose administered simultaneously. After subchronic exposure to dietary cadmium for 4 weeks the retention of iron was increased if iron was administered alone or together with cadmium in comparison to normal controls. If iron was administered alone to subchronically treated animals, iron retention was of the same order of magnitude as in iron-deficient controls. However, if iron was administered together with cadmium (molar ratios 1/0.5, 1/1, 1/2 mumol/kg body wt) the retention of iron was decreased in a dose-dependent manner. The iron content in the liver and spleen of acutely exposed rats decreased, whereas the tissue content of the treated rats increased according to the increased body retention of iron. The utilization of iron for hemoglobin synthesis remained unchanged in all groups investigated. PMID- 4029059 TI - Sewage effluent biomonitoring. I. Survival, growth, and histopathological effects in channel catfish. AB - A 17-day, in situ, biomonitoring study using caged, juvenile channel catfish (Ictalurus punctatus) was conducted at five sites along a 9-km section of the Flint River at the Anthony Ragnone Wastewater Treatment Plant near Montrose, Michigan. Effects on survival, growth, and gill and liver histopathology were examined. No differences in growth, measured as wet weight gain, were observed between upstream control (UP) and experimental fish located 9 km downstream from the outfall (Down 4). Acute, 100% mortality occurred at study sites 300 and 500 m downstream from the outfall (Down 1 and Down 2, respectively). Mortality was probably due to excessive mean total residual chlorine concentration (0.24 and 0.30 mg/liter at Down 1 and Down 2, respectively). No mortality was observed at the remaining study sites. Forty percent of the fish at UP had slight hyperplasia and hypertrophy of the respiratory epithelium. All fish at Down 4 had two or more moderate to severe histopathological damages to the gills, including severe hyperplasia of the epithelial cells, clubbing and fusion of the secondary lamellae, moderate to severe edema in the secondary lamellae, and multiple, blood filled aneurysms. Thirty-eight percent of livers from the UP fish were extremely vacuolated compared to 60% of the Down 4 fish livers. Both the vacuolated and less vacuolated (dense) liver sections stained negatively for lipids with oil red O. The vacuolated liver sections were qualitatively more intense than the dense sections when stained with Best's carmine. Vacuolated liver sections stained negatively with Best's carmine when pretreated with amylase, thereby indicating that the vacuolation represented glycogen storage. There was no correlation between the histopathological changes and any deleterious effects on growth or survival during the 17-day exposure. However, the gill histopathological changes would likely increase susceptibility to bacterial gill disease, and cause a reduction in the scope for activity due to impaired oxygen diffusion in the gills. PMID- 4029060 TI - Absence of initiating activity by quercetin in the rat liver. AB - Initiating activity of quercetin was tested in rats which were treated with partial hepatectomy and given a liver cancer promoter, phenobarbital. A few intestinal neoplasms were seen but without significant difference in incidence from those in the quercetin-untreated group. Moreover, neither neoplastic nor preneoplastic liver changes were detected in quercetin-treated groups. With hepatocyte primary culture/DNA repair test, quercetin did not produce genotoxicity. The results show that quercetin has no initiating or genotoxic activities in the rat liver. PMID- 4029062 TI - [A course for continuing medical education]. AB - To promote continuing medical education, the Central Military Hospital of Mexico offers a course in which the student may develop his skills for finding and using sources of information, applying the scientific method to biomedical research, and communicating the results thereof in writing. The methodology is more self instructional than expository. The course program is divided into three modules geared to the general objectives, and the duration varies between 10 and 14 weeks. The course is attended in the final stage of the professional training, when the student has just completed his specialization, or when he is beginning it, on the premise that this is the best time to make clear to the physician the need to continue studying and learning throughout life. The author of this article explains why the course is important, states its specific objectives and, in an annex, presents the content of the program. PMID- 4029061 TI - Compartmentalization and persistence of endothall in experimental pools. AB - The compartmentalization and persistence of endothall, an aquatic herbicide, was studied using static greenhouse experimental pools. An overall aqueous pseudo first-order decay rate coefficient of 0.173 day-1 and a half-life of 4.01 days were observed at endothall treatment levels of 0.03, 1.6, and 4.5 mg liter-1. Instantaneous sediment partition coefficients (Kp) were calculated at maximum endothall concentrations in sediments and ranged from 51.4 to 127.7. Bioconcentration factors (BCF) for the submerged aquatic macrophyte, Myriophyllum spicatum, ranged from 3.9 to 768.9. These instantaneous BCF values were calculated at the maximum M. spicatum endothall concentrations. The short aqueous half-life for endothall compares well with previous studies; however, both the Kp and BCF were one to three orders of magnitude higher than observed in a previous laboratory study and calculated from regression equations based on endothall solubility. Experimental pool studies can be important steps in translation of data from the laboratory to field and in the development of field sampling protocols that require understanding of expected behavior of a chemical in aquatic systems. PMID- 4029063 TI - [A contemporary model of environmental health sciences: its application in the recruitment of faculty and in academic development]. AB - The authors describe the development and application of an intellectual model fitted to the environmental health sciences. The model became the basis for the design of a new study plan in addition to providing the strategy for recruitment of the faculty for the new School of Public Health of the San Diego State University in San Diego, California. They give an account of the circumstances leading up to the establishment of this institution, the gradual consolidation of the different health science programs into a single school with graduate studies leading to masters degrees in six main fields: environmental health, occupational health, epidemiology, maternal and child health, health services administration, and health development. The authors see the beginning of a redefinition of the function of the basic sciences represented in environmental health in the light of new knowledge and technology, and believe that all fields of knowledge (microbiology, parasitology and health development) will contribute as a unified whole to increase the capacity of public health to place both biological and environmental health problems in a context that society can control. PMID- 4029064 TI - [Teaching methods and the improvement of education in health administration]. AB - This article raises two basic problems that health administration educators must face in drawing up study plans and selecting pedagogical methods for the proper training of local-level health administrators. One problem is the theory of administration--influenced by scientific theories from other disciplines--and the other is the many objectives of instruction in this field. Some of the factors are examined that have helped prevent the development in health administration instruction of a clear perception that would enable it to identify the problems, methodologies and appropriate solutions at the local level everywhere; this lack of clarity naturally gives rise to a series of conflicts about the educational requirements and those of the administration process itself. The primary activities of a local administrator and the nature of the student's motivation and his objective have to be borne in mind in the context of the teaching and learning experience. The author feels that, apart from considerations on social justice, the right road to the improvement of instruction in this field is essentially to choose the best pedagogical technology for the type of student to which it is addressed. PMID- 4029065 TI - [Current participation of the nurse in the activities covered in the "expanded role of nursing"]. AB - The article reports on a survey conducted in Colombia to evaluate the part played by the nurse in the functions covered by what has come to be called "the expanded role of nursing." According to the survey, there are 2,213 practicing nurses, who are clustered in the principal cities of the country. Those who participated in the study are young nurses holding staff positions in such institutions as university and social security hospitals. Their training is mostly at the university level, and they have had five years or less of experience. The article notes that, to perform the duties of the expanded role, the nurse must participate in accordance with her training, interest and motivation. The participation may be conditioned by factors in the nurse herself (prior knowledge, former training, previous participation, and responsibility) and by factors in the working environment (the person who instructed her on her role, the post she holds, her length of service/length of her work day, permission received from the institution to exercise her function, and the medical and nursing agreement). Parodoxically, the nurse is being made a participant in new functions at hospitals where there are medical resources and not in regions and places where those resources are scarce or nonexistent. The expanded role of nursing opens to the nurse a range of activities that enable her to provide quality care to the patient and to his or her family and community, to extend the coverage of health services, and offer treatment effectively. PMID- 4029066 TI - [Challenges of the future in pharmacology]. PMID- 4029067 TI - [Hemodynamic changes as affected by isotheoline]. PMID- 4029068 TI - [Regression of experimental cholesterol-induced atherosclerosis in rabbits after stopping the atherogenic diet and after treatment with nicotinic acid]. PMID- 4029069 TI - [Ultrastructure of the thymus epithelial cells in the early stage of human prenatal development]. PMID- 4029070 TI - [Purple membranes as a model system for research on photoreception processes. I. The structure, asymmetry and dynamics of the purple membrane]. PMID- 4029071 TI - [Experimental research on the hepatoprotective activity of drug combinations]. PMID- 4029072 TI - [Preliminary construction and validation of an anxiety scale derived from the French version of the AMDP, the AMDP-AT]. AB - The authors have applied to 493 Belgian and French patients the French version of the AMDP Psychopathology and Somatic scales, made of 140 items from the original German version and of 22 items specific to its French adaptation, among others anxiety items. By applying a principal components factor analysis to this sample, a 17-items. Anxiety Scale was extracted from the 162-items complete scales. This new scale is characterized by a predominence of tension/irritability items over somatic items as compared to the Hamilton Anxiety Scale. On 116 cases, the correlation between both scales is .59 (p less than .0001). A cut-off score for anxiety and an inclusion score for drug trials are suggested on the basis of statistical data. PMID- 4029073 TI - [Melatonin. Chronobiologic peripheral endocrine index in depressive states]. AB - The chronobiological studies with melatonin constitute valid arguments to consider melatonin as a peripheral index of depressive disorders. In a group of patients with major depression, we reported a lowering of melatonin nocturnal plasma levels, associated with cortisol hypersecretion. A similar lowering of melatonin was observed in a group of patients with cluster headaches, but without quantitative modification of cortisol secretion. Other studies are necessary in order to determine wether melatonin may be considered as a "state marker" of depression itself or a marker of the genetic vulnerability to depression. PMID- 4029074 TI - [Lewis-negative blood group. Definite frequency, probable prognostic value in adult psychiatry]. AB - The negative Lewis blood type is meaningfully more frequent with our psychiatric patients than with the general population. The theoretical interest of this fact is certain for the reason of two particularities of this blood type. It is not genetically and definitely determined at birth: the absence of passing over negativity through positivity seems to constitute a factor in favour of the blossoming of a psychiatric pathology. It is in connection with the secretory aptitude of some cells: this fact opens some perspectives for the comprehension of the deficits in the neurotransmitters. The application of theory will be confirmed by others statistics. But it indeed appears that the control of the chemiotherapy is more difficult with the negative Lewis blood type patients. PMID- 4029075 TI - [Study of cerebral blood flow by the xenon-133 method in 10 schizophrenic adolescents]. AB - Regional cerebral blood flow (r CBF) was compared in ten adolescents with hebephrenia who were never treated with neuroleptics and ten normal controls using the Xenon 133 inhalation method. There were no differences in mean hemispheric blood flow. The main difference was the loss of the "hyperfrontal pattern" in the schizophrenics: the prefrontal values were only 0.7% greater than the blood flow in the rest of the hemisphere, compared with 14.6% in the controls. PMID- 4029076 TI - [Platelet monoamine oxidase and sex hormones in a population of depressed patients]. AB - The association between changes in platelet MAO activity and Major Depressive Episode have been demonstrated. Cyclical changes in sex hormones serum levels had never been related with changes of MAO activity in depressed patients. Platelet MAO activity, oestrogen serum levels, progesterone serum levels and testosterone serum levels, have been measured in drug free depressed patients: 22 men and 42 women. This study demonstrates no relationship between serum levels hormons and platelet MAO activity, measured in men and in women. If young women are separated from menopaused women, platelet MAO activity is negatively correlated with oestrogen serum levels, in non menopaused women. Significance of this variation in studies about the use of MAO as a biochemical marker in depression is discussed. PMID- 4029077 TI - [Anorexia nervosa: the plate and the scanner]. PMID- 4029078 TI - Slow metabolic clearance rate of the 20,000-dalton variant of human growth hormone: implications for biological activity. AB - The 20,000-dalton variant of human GH (hGH) (20 K) exhibits full growth-promoting bioactivity in the rat despite its poor interaction with GH receptors, as compared to the principal 22,000-dalton form of hGH (22 K). To test the possibility that prolonged survival time of 20 K in vivo may contribute to this apparent discrepancy, we compared the MCRs of 22 K and 20 K in the rat by the single injection technique. Both radiolabeled and native 22 K and 20 K were examined in this regard. The MCR of 20 K was 2- to 3-fold lower than that of 22 K, a statistically significant difference (P less than 0.05). The distribution volumes were similar for the two hGH forms and corresponded approximately to the extracellular fluid space. We conclude that the prolonged persistence of 20 K in the circulation may contribute to its higher than expected bioactivity in vivo in the rat. PMID- 4029079 TI - Estrogen regulates low density lipoprotein metabolism by cultured swine granulosa cells. AB - To test estrogen's possible regulation of lipoprotein metabolism by granulosa cells, swine granulosa cells were cultured under serum-free conditions in the presence or absence of estradiol. Treatment with estradiol significantly enhanced high affinity, saturable, [125I]iodo-low density lipoprotein (LDL) binding with a median 2.85-fold (range 2.3- to 5.6-fold, n = six experiments) increase in the calculated number of LDL receptors and no change in the apparent dissociation constant (Kd) for LDL binding (Kd = 3.4 +/- 0.92 micrograms/ml in control and 4.0 +/- 0.87 micrograms/ml human LDL in estradiol-treated cultures). Estradiol also significantly increased [125I]iodo-LDL internalization by granulosa cells and augmented the maximal rate of LDL degradation by 2.0 to 2.5-fold without altering the apparent Michaelis-Menten constant (Km) for this process. Estrogen's dose dependent enhancement of [125I]iodo-LDL binding, internalization, and degradation could be observed at minimum estradiol concentrations of approximately 100 ng/ml and was accompanied by increased progesterone secretion by granulosa cells. Further studies indicated that estrogen's stimulation of LDL internalization and degradation was not simply attributable to increased rates of nonspecific bulk fluid-phase pinocytosis (assessed with [125I]iodo-polyvinylpyrrolidone) or increased steroidogenesis per se (tested by blocking cholesterol side-chain cleavage with aminoglutethimide). We conclude that estradiol amplifies LDL binding by swine granulosa cells by increasing the number of high affinity, saturable LDL receptors with no alteration in their apparent affinity. Moreover, estrogen action is accompanied by enhanced rates of progesterone production in the presence of LDL, and increased rates of LDL internalization and degradation, which could not be accounted for simply by accelerated nonspecific bulk fluid phase pinocytosis. We suggest that the significant facilitative actions of estradiol on lipoprotein binding and metabolism are likely to assist in preparing granulosa cells for the increased rates of progesterone biosynthesis ultimately required in functional corpora lutea. PMID- 4029080 TI - Specific binding of estrogen and estrogen-receptor complex by microsomes from estrogen-responsive tissues of the rat. AB - Rat uterine and anterior pituitary microsomes each contain a population of specific estrogen-binding sites. Saturation binding of estradiol is demonstrable, with an affinity similar to that of the cytosol estrogen receptor (Ka = 1-2 X 10(10) M-1). Dissociation rate kinetic determinations, however, revealed that estrogen-microsomal complexes are 4 times as stable as cytosol estrogen-receptor complexes. Sedimentation properties in sucrose gradients were salt-dependent, yielding values of 10S in KCl-free buffer and 5.5S in the presence of 0.4 M KCl. The concentration of microsomal sites varies in proportion to the level of cytosol estrogen receptor, such that microsomal binding constitutes a consistent 20% of the total extranuclear binding capacity. Binding is sensitive to pronase, but not to ribonuclease or deoxyribonuclease; steroidal specificity differs from cytosol receptor only with respect to a greater extent of competition by progesterone. Microsomal binding sites are readily extractable with KCl-free hypotonic buffer or with 0.4 M KCl, but are resistant to extraction by 0.15 M KCl. The presence of estradiol lends stability to the microsomal binding sites, while high salt has a deleterious effect on their longevity. After exhaustive extraction of binding sites, microsomes are capable of accepting cytosol estradiol-receptor complexes to a level corresponding to the concentration of depleted binding sites; microsomes from nontarget tissue do not manifest such capability. However, the original microsomal estrogen-binding sites are not simply cytosol receptor contaminants, as evidenced by the observations that the microsomal binding site concentration is independent of the volume of tissue homogenate (indicating that a trapping phenomenon is not operative) and that nonextracted microsomes are not potential acceptor sites for cytosol estradiol receptor complexes. In considering total cellular dynamics of estrogen and estrogen receptor turnover, it thus becomes important to explore the role of the microsomal compartment, since it functions as a repository of specific estrogen binding sites and may have significant acceptor capability for the cytosol estrogen-receptor complex. PMID- 4029081 TI - [3H]cortivazol: a unique high affinity ligand for the glucocorticoid receptor. AB - Cortivazol (CVZ) and deacylcortivazol (DAC) are pyrazolosteroids with potent glucocorticoid activity. In previous work we showed that DAC is 40-fold more potent than dexamethasone (DEX) in lysing leukemic lymphoblasts. To assess the interaction between these atypical steroids and the glucocorticoid receptor, we examined the binding of [3H]CVZ to cytosol from glucocorticoid-sensitive and resistant variants of the human leukemic cell line CEM C7. In glucocorticoid sensitive cells [3H]CVZ causes a 2-fold induction of glutamine synthetase and binds to a protein in the 4.6 S region of high salt sucrose gradients. On DEAE cellulose chromatography, [3H]CVZ-receptor complexes show a shift from high (0.25 M KP) to low salt (0.09 M KP) eluting forms upon activation. CVZ competes for a 97,000-dalton protein labeled by [3H]dexamethasone mesylate. Scatchard analysis of the binding of [3H]CVZ in glucocorticoid-sensitive cells revealed a curvilinear plot which resolved into high (0.4 nM) and low (11 nM) affinity components. The receptor concentration of the low affinity site (0.30 pmol/mg protein) was approximately twice that of the high affinity site (0.14 pmol/mg protein). Dissociation experiments with dilution and/or excess unlabeled CVZ supported the presence of independent sites. In contrast, the binding of [3H]DEX to C7 cytosol revealed a single class of binding sites (Kd = 1.9 nM; receptor concentration, 0.46 pmol/mg protein). Examination of the binding of [3H]CVZ using 10(-5) M DEX as the competing ligand showed that DEX binds only to the low affinity site detected by [3H]CVZ. In cytosol from a glucocorticoid-resistant cell line with virtually no [3H]DEX binding, [3H]CVZ detected a single high affinity binding site that was similar in dissociation constant (0.8 nM) and receptor concentration (0.13 pmol/mg protein) to the high affinity site detected in the glucocorticoid-sensitive cell line C7. PMID- 4029082 TI - The effect of gastrin-releasing peptide on growth hormone secretion in the rat. AB - Several investigators have reported gastrin-releasing peptide (GRP)-like immunostaining in several regions of the rat brain. The objective of this study was to determine the possible effects of this peptide on GH release. Porcine GRP was injected intraventricularly (third ventricular) in a volume of 2 microliters into ovariectomized female rats. A significant decrease in basal GH release, as evidenced by decreased plasma GH levels, was observed within 10 min which lasted for 90 min after the injection of 2 micrograms (0.7 nmol) GRP (P less than 0.001). In addition, all GH pulses were abolished during this time. In subsequent experiments, varying doses of GRP were administered, and human pancreatic GH releasing factor (GRF) was injected iv at a dose of 0.1 microgram/kg 20 min later to determine the responsiveness of the pituitary. The minimal effective dose of GRP to lower plasma GH was approximately 10 ng (3.6 pmol); however, the GH releasing action of GRF was blocked by even the lowest dose of the peptide tested (5 ng; 1.8 pmol). To determine if GRP had any direct action on the pituitary, overnight-cultured pituitary cells from ovariectomized animals were incubated for 1 h with GRP in various concentrations. There was a slight dose-dependent stimulation of GH release with concentrations of GRP ranging from 10(-9)-10(-6) M; however, the GH-releasing action was much less than that of GRF. To confirm the direct stimulatory effect of GRP on GH release, dispersed pituitary cells were perifused with medium containing 2 X 10(-6) M GRP. An immediate increase in GH release was observed in the perfusate. Since GRP has a direct stimulatory action to release GH in the pituitary, but ivt injection of the peptide inhibits GH release and blocks the response to GRF, we suggest that GRP may act on periventricular structures to release somatostatin, which reduces GH release and blocks the response to GRF. PMID- 4029083 TI - Selection and characterization of a breast cancer cell line resistant to the antiestrogen LY 117018. AB - We have selected and cloned a stable variant of the MCF-7 human breast cancer cell line (LY 2) that is resistant to LY 117018 (LY), a potent antiestrogen that inhibits cell growth at concentrations as low as 10(-10) M. The cell line was selected by increasing the concentration of LY in the growth medium in a stepwise manner from 10(-8) to 10(-6) M as the cells become resistant. LY2 has been cloned in soft agar and carried for over 50 passages with no change in resistance. Other antiestrogens, such as tamoxifen and 40-hydroxytamoxifen no longer inhibit cell proliferation of LY 2. The cell line is still responsive to estrogen in a cell proliferation assay, but contains somewhat less estrogen receptors than MCF-7. The cytosolic estrogen receptor sediments to a 4S position on high salt sucrose density gradient centrifugation and is completely shifted to a denser gradient region when the receptor is incubated with a monoclonal antiestrophilin. The nuclear estrogen receptor when covalently labeled with [3H]tamoxifen aziridine has the same mol wt (62,000) in both MCF-7 and LY2 cells, when determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. In a competitive binding assay, LY 117018 competes for [3H]estradiol binding to its cytosol receptor with the same Ki in both MCF-7 and LY2 cells. When the induction of estrogen-specific proteins was examined, no detectable progesterone receptor could be detected in either estrogen-induced or control LY2 cells, in contrast to MCF-7 cells. However, both 52,000- and 160,000-dalton proteins were estrogen inducible in the medium of LY2 and MCF-7 cells, as measured by labeling with [35S]methionine. The phenotypic stability of the antiestrogen resistance in LY2 cells coupled with the cross-resistance the antiestrogens of widely different structures make this cell line an ideal model system for the study of hormone resistance in human breast cancer. In addition, while the mechanism of resistance is currently not elucidated, the selective loss of estrogen-inducible functions in this cell line may provide powerful clues for future study. PMID- 4029084 TI - In vitro synthesis and secretion of ovine trophoblast protein-1 during the period of maternal recognition of pregnancy. AB - The trophoblast of the sheep conceptus secretes a low mol wt, acidic polypeptide called ovine trophoblast protein-1 (oTP-1) from days 13-21 of pregnancy. This protein has been proposed to have an antiluteolytic role during pregnancy, since infusion of oTP-1 into the uterine lumen of nonpregnant ewes lengthened their estrous cycles. In the present study, mRNA from day 16 conceptuses was translated using a cell-free wheat germ lysate, and oTP-1 was immunoprecipitated from the translation mixture by means of a specific rabbit antiserum. The predominant protein synthesized under these conditions was oTP-1, which had a mol wt (21,000) higher than that of oTP-1 secreted by intact conceptuses into culture medium (mol wt, 17,000). In a separate experiment, in vitro secretion of oTP-1 from conceptuses on days 13, 17, and 21 of pregnancy was examined. Conceptuses were cultured for 24 h in the presence of [3H]leucine, and oTP-1 was immunoprecipitated from the culture medium. Incorporation of [3H]leucine into secreted macromolecules (mol wt, greater than 3500) increased 12-fold from days 13 to 21, while release of immunoprecipitable 3H-labeled oTP-1 increased 27-fold from days 13 to 17 and declined by over 50% from days 17 to 21. When results were expressed per microgram DNA, secretion of total macromolecules declined from days 13 to 17 and then remained constant until day 21. The pattern of oTP-1 secretion held whether results were expressed per conceptus or per unit DNA. The interestrous intervals for the donor ewes were shorter for ewes which had their conceptuses removed on day 13 than for ewes flushed on day 17 or 21. Thus, the period of oTP-1 synthesis corresponds closely to the time at which the conceptus acts to extend luteal lifespan. PMID- 4029085 TI - Effect of thyroid hormone supplementation on survival after bacterial infection. AB - During nonthyroidal illness in man and a number of experimental animals, serum total thyroid hormone levels are decreased. To determine whether the reduction in thyroid hormones that occurs during nonthyroidal illness is beneficial or harmful to the host, an experimental animal model was developed. Male Sprague-Dawley rats were infected with Streptococcus pneumoniae type I, a known human pathogen. By 40 h after inoculation, serum total and free T4 and total T3 decreased significantly. Serum free T3 also decreased slightly but not significantly. When infected animals were injected daily with T4, there was a decrease in the time to death and significant increase in the total number of deaths compared to controls receiving vehicle alone. Control experiments showed that T4 did not affect the growth of S. pneumoniae on blood agar plates, and the injected T4 did not cause hyperthyroidism. These results suggest that the decrease in serum thyroid hormone that occurs during nonthyroidal illness is beneficial and may serve a role in maintaining homeostasis by conserving metabolic energy during infection as an important adaptation that prolongs survival. PMID- 4029086 TI - Variables determining the growth hormone response of His-D-Trp-Ala-Trp-D-Phe-Lys NH2 in the rat. AB - Previous studies of His-D-Trp-Ala-Trp-D-Phe-Lys-NH2 (GH-RP-6) have shown this synthetic hexapeptide to be a potent and specific stimulator of GH secretion both in vivo and in vitro. In this study the variables determining the in vivo responses were examined in the rat. The magnitude of the GH response to sc GH-RP 6 was dependent on the age and sex of the rat. Animals less than 15 days of age had much larger responses than did rats 21 days and older. At 10 days of age the male rat had a larger GH response than the female. At 21 days of age, bis(4 methyl 1-homo-piperazinyl-thiocarbonyl) disulfide (Fla-63)-pretreated females had larger responses than did Fla-63-pretreated males. In the Fla-63-pretreated adult rat, sc GH-RP-6 stimulated GH release in the female but not in the male. In the 10-day-old male, the ED50 for sc GH-RP-6 was 0.4 micrograms, and the maximal serum GH response was 800 ng/ml. In the 21-day-old female Fla-63-pretreated rat, the ED50 for sc GH-RP-6 was 3.0 micrograms, and the maximal GH response was 200 ng/ml. In the 21-day-old female pentobarbital-anesthetized rat, iv GH-RP-6 had an ED50 of 0.5 micrograms and a maximal serum GH response of 2500 ng/ml. A marked dose- and time-dependent decrease of subsequent GH-RP-6 responses occurred after a single sc GH-RP-6 injection. Decreases in pituitary GH or increases in somatostatin secretion would not explain this decreased response because the GH response of MRZ 2549, an opiate agonist, was unchanged by GH-RP-6 pretreatment. In contrast to the acute effect of GH-RP-6, chronic daily injections of GH-RP-6 resulted in an enhancement of the GH-RP-6 response. PMID- 4029087 TI - The electrical properties of isolated human prolactin-secreting adenoma cells and their modification by dopamine. AB - Human prolactinoma cells were maintained in culture for a period of at least 8 days and were able to secrete PRL in large amounts. This secretion was inhibited by bromocriptine, an agonist of dopaminergic receptors, in a dose-dependent manner. The cells showed electrical activity (action potentials) which was blocked by inhibitors of calcium current (cobalt, manganese), whereas it was insensitive to blockers of sodium current (tetrodotoxin). At the resting potential of the cell, dopamine induced a hyperpolarizing response such that action potentials no longer occurred. This effect was due to increase of the membrane conductance and depended on the cell potential. The reversal potential of this response was at -100 mV, which suggests the involvement of potassium ions. Bromocriptine and RU 24213, which are strong dopaminergic receptor agonists, both induced responses identical to the dopamine-induced response. The D2 receptor antagonists (haloperidol, domperidone, and spiperone) blocked the dopamine-induced response in a reversible manner. The D1 antagonist of dopaminergic receptors flupentixol had no effect on the dopamine response. It is concluded that the dopamine modulation of electrical activity involving calcium current may be an early important step in the mechanism by which dopamine inhibits PRL release. PMID- 4029088 TI - Effects of aluminum on bovine parathyroid adenylate cyclase. AB - It is known that the secretion of PTH is often impaired in association with aluminum (Al3+) accumulation in patients with renal failure. The mechanisms involved remain ill defined. Since adenylate cyclase plays a role in the regulation of PTH secretion, these studies examine the effects of Al3+ on parathyroid adenylate cyclase. In membranes from normal bovine parathyroid glands, basal adenylate cyclase activity, in the presence of 0.2 mM ATP and 20 mM Mg2+, increased by 22% as Al3+ was raised from 0-10 microM. Higher Al3+ concentrations caused a progressive decrease in adenylate cyclase activity, reaching 68% inhibition of control activity at 2 mM Al3+. Since adenylate cyclase activation is influenced by the interaction of multiple sites within the adenylate cyclase complex, the nature of the inhibition by Al3+ was explored by examining the interaction of Al3+ with substrate ATP and with Mg2+, an allosteric activating metal ion. In the presence of 20 mM Mg2+, Al3+ concentrations of 1-2 mM resulted in noncompetitive inhibition with respect to ATP [decrease in maximum velocity (Vmax) from 4176 in the absence of Al3+ to 1106 pmol cAMP/mg protein X 15 min; Michaelis Menten constant (Km) for ATP was unchanged]. In contrast, at fixed ATP (0.2 mM), 0.5 mM resulted in competitive inhibition of adenylate cyclase with respect to Mg2+, whereas at higher Al3+ concentrations the inhibition was noncompetitive. When Mg2+ was replaced by Mn2+ (enzyme activity reflects the activity of the catalytic unit), the inhibitory effect of Al3+ on adenylate cyclase activity was abolished. These data suggest that the inhibition of parathyroid adenylate cyclase by Al3+ occurs at the level of the allosteric metal activating site. These data provide a potential mechanism for the inhibition of PTH secretion by Al3+. PMID- 4029089 TI - Thionapthene-2-carboxylic acid: a new antihypercalcemic agent. AB - Thiophene-2-carboxylic acid (TCA) was previously shown to be hypocalcemic in the rat. We have compared TCA with thionapthene-2-carboxylic acid (TNCA), an analog which is a more potent inhibitor of bone resorption in vitro, for the ability to decrease serum calcium concentration in vivo. In normocalcemic rats on a low calcium diet, TNCA (2 mmol/kg) produced a larger and more prolonged decrease in calcium concentration than TCA. In rats bearing the Walker 256 carcinosarcoma, which became hypercalcemic, TNCA produced a dose-related decrease in serum calcium concentration at 0.3-1.2 mmol/kg. TNCA reduced serum calcium concentration in 4-6 h, and the effects were sustained for up to 72 h. TNCA was effective after oral as well as sc administration. Unlike calcitonin which produced only a transient reduction in serum calcium followed by escape, the effects of TNCA (0.6 mmol/kg) were sustained for 1 week and were accompanied by a decrease in mortality in tumor-bearing animals. We conclude that TNCA is a potent hypocalcemic action which has a rapid and prolonged effect without evidence of escape. This and related compounds should be tested further for use in treatment of hypercalcemia and other states characterized by excessive bone resorption. PMID- 4029090 TI - Intracellular processing of prolactin. AB - PRL has been reported to exist as a number of mol wt and charge variants. We have attempted to determine the relationships among the charge and lower mol wt variants by two-dimensional gel analysis of pituitary and pituitary cell extracts. Silver-stained gels of the extracts showed three major charge isoforms of 24,000 mol wt PRL (PRLs 1, 2, and 3, with PRL 3 being the most anodic) and what appeared to be an arc of products originating in the region of PRL 3. Each spot in the arc was distinct and represented a small decrease in size (two to eight residues), with a corresponding increase in net negative charge. When primary cell cultures were labeled with [35S] methionine, the three PRL isoforms and arc products were detectable by autoradiography. Western blots of the two dimensional gels showed the arc products to be immunologically related to PRL. Treatment of the cell cultures with hydroxynorvaline (5 mM), which inhibits processing of pre-PRL to PRL, resulted in doublet spots in the arc. Elimination of protease inhibitors or an increase in temperature during protein isolation had no effect on the relative concentrations of PRL and arc products. Inclusion of standard PRL or [125I]iodo-PRL in the extraction solution did not increase the size of the spots in the arc or produce labeled arc products, respectively. Treatment of the cell cultures with chloroquine (10(-5) M) before and during radiolabeling had no effect on the production of radiolabeled arc products. Analysis of cell culture medium showed at least some of the arc products to be secreted. We conclude that PRL or a PRL-like molecule is processed intracellularly into a number of smaller derivatives. As the arc products accumulate within the cell and are secreted, we suggest that they may be biologically important relatives of PRL. PMID- 4029091 TI - Hypercalcemia in rats bearing growth hormone- and prolactin-secreting transplantable pituitary tumors. AB - We evaluated the effects of chronic massive elevations of serum GH and PRL on calcium metabolism in rats bearing the MStT/W15 and 7315a transplantable pituitary tumors. MStT/W15 tumor rats manifest elevated serum GH and PRL levels, hypercalcemia, hypercalciuria, and elevated serum levels of PTH and 1,25 dihydroxyvitamin D. The hypercalcemia was not reversed by dexamethasone or propranolol treatment, but was ameliorated by starvation. Parathyroidectomy produced hypocalcemia in the MStT/W15 tumor rats, confirming the parathyroid dependence of the hypercalcemia. The 7315a tumor produced a milder degree of hypercalcemia, along with elevated serum levels of PRL, ACTH, and corticosterone; serum GH was normal. In high concentrations, PRL and/or GH may stimulate the secretion of PTH as well as enhance dietary calcium absorption, in part through the mediation of 1,25-dihydroxyvitamin D. PMID- 4029092 TI - Dynamic features of luteal secretory granules: ultrastructural changes during the course of pregnancy in the cow. AB - The ultrastructure of large and small cells from corpora lutea of pregnant cows (days 45-280) were evaluated by electron microscopy. The distinguishing features of small cells (10-15 micron in diameter) included stacks of rough endoplasmic reticulum, whorls of smooth endoplasmic reticulum, elongated mitochondria containing crystalline-like inclusions, and cytoplasmic lipid droplets. The large cells (20-50 micron in diameter) contained numerous mitochondria packed tightly together (no elongated structures), an abundance of smooth endoplasmic reticulum (no whorls), and a large number of membrane-bound secretory granules (150-300 nm in diameter). These granules appeared to be packaged in the Golgi, accumulated at a paranuclear region, and migrated as a group to the cell membrane where they were exocytosed. These granules were first observed on day 45 and increased in number to reach a peak around day 200. Lipid droplets became a common cytoplasmic inclusion in the large cells during the third trimester of pregnancy. In addition, during this stage, an electron-dense substance began to accumulate in the mitochondria to such an extent as to occlude the cristae. These mitochondria looked like large (500-1800 nm) membrane-bound granules; however, they did not undergo exocytosis. Their appearance in large cells during the last 3 months of pregnancy may reflect a change in steroid metabolism. Thus, there are two morphologically distinct cell types throughout pregnancy in the cow. The large cell containing the secretory granules underwent what appeared to be a progressive state of apparent deterioration with advancing pregnancy. The morphology of the small cell did not undergo such a dynamic change. No morphological evidence was observed that would support a transition state between the two cell types. PMID- 4029093 TI - Delayed pulmonary maturation in the fetus of the streptozotocin-diabetic rat. AB - Pulmonary maturation was studied in fetuses in streptozotocin-diabetic rats on the final four days of gestation. Diabetes was induced prior to conception by the intravenous injection of streptozotocin. Fetuses were hyperglycemic but did not manifest hyperinsulinemia. Whole lung total phospholipid, phosphatidylcholine, and disaturated phosphatidylcholine were significantly decreased in the diabetic group on day 21 (term = 22 days), but not prior to or after that point in gestation. Morphologic analysis also revealed a decreased number of type II cells and lamellar bodies per alveolar lining cell in the diabetic group only on day 21, coincident with the changes in phospholipid analysis. Activities of enzymes involved in fetal pulmonary phospholipid synthesis were measured to see if differences could account for the observed developmental delay. No significant differences between diabetic and control lungs were noted in any of the enzymes studied from days 20-22, with the exception of an increase in cholinephosphate cytidylyltransferase activity in the diabetic fetuses on day 22. Immaturity in both biochemical and morphologic indices of lung development was present at a specific time late in the diabetic rat gestation. This maturational delay could not be accounted for by changes in the activities of enzymes involved in phospholipid synthesis. The fetus of the streptozotocin-diabetic rat provides a useful model to study the effects of hyperglycemia on fetal lung development. PMID- 4029094 TI - Cyclophosphamide-induced depression of the antioxidant defense mechanisms of the lung. AB - Cyclophosphamide causes lung toxicity in a wide variety of animals, including humans. Recent evidence suggests that oxygen (O2) potentiates cyclophosphamide induced pulmonary injury. We hypothesized that cyclophosphamide or one of its toxic metabolites, acrolein, may potentiate O2 toxicity by depressing lung antioxidant defense mechanisms. To test this, we gave rats cyclophosphamide (100 mg/kg), acrolein (5 mg/kg), or a vehicle (control) in a single intraperitoneal injection and then killed them during a 5-day study period. Excised lungs were analyzed for reduced glutathione (GSH) content, glucose-6-phosphate dehydrogenase (G6PD), glutathione reductase (GSH-R), glutathione peroxidase (GSH-P), and superoxide dismutase (SOD) activities. In the lungs of cyclophosphamide-treated rats, GSH content was increased 48% (P less than 0.001) on day 2 but progressively decreased to 50% of control values (P less than 0.001) on day 5. Significant reductions (P less than 0.005) in G6PD, GSH-R, and GSH-P activities occurred on days 1-5, and SOD activity was significantly decreased (P less than 0.005) on days 4 and 5 by cyclophosphamide. In acrolein-treated rats, GSH content and GSH-R, GSH-P, and SOD activities were indistinguishable from those in controls. However, G6PD was increased (35-38%) on days 2 and 3 but returned to control values thereafter. To assess whether the cyclophosphamide-induced reduction in lung antioxidant defenses increased susceptibility to acute O2 toxicity, we gave a separate group of rats cyclophosphamide, acrolein, or vehicle, and 4 days later exposed them to 100% O2 or air at 1 atmosphere absolute. All cyclophosphamide-, acrolein-, and vehicle-treated rats survived 60 h air exposure, and all vehicle-treated rats exposed to 100% O2 survived. In contrast, all of the cyclophosphamide-treated rats exposed to 100% O2 died (P less than 0.05) within 40 h. Acrolein had no effect on survival in 100% O2. These results indicate that cyclophosphamide, but not acrolein, depresses lung antioxidant defense mechanisms, which may be responsible for increased mortality from O2 toxicity in cyclophosphamide-treated animals. PMID- 4029095 TI - Respiratory bronchiolitis following long-term ozone exposure in bonnet monkeys: a morphometric study. AB - To quantitate the response of respiratory bronchiolar (RB) epithelium and peribronchiolar connective tissue (PCT) to chronic exposure to high ambient levels of ozone, two groups of 8 adult male bonnet monkeys each were subjected 8 h daily for one year to 0.64 ppm (UV standard) ozone or filtered air, respectively. Blocks of tissue selected throughout the lung and from first generation RBs following airway microdissection had the following significant exposure-related changes: 57% greater volume of RB in the lung, 27% smaller diameter of RB lumen, 179% thicker media and intima of peribronchiolar arterioles, 61% thicker RB epithelium, and 77% thicker PCT. The increase in thickness of the RB wall resulted primarily from an 84% increase in PCT, with the remainder from the epithelium. Estimates of cellular numerical density showed an 81% increase in cuboidal bronchiolar cells and an 87% decrease in type 1 pneumocytes in the exposed group. Cell volumes from serial section reconstruction showed significantly larger cuboidal bronchiolar (79%), ciliated (117%), and type 2 (66%) cells over controls. Significant PCT changes included more amorphous extracellular matrix (288%), neutrophils (1523%), and lymphocytes/plasma cells (307%). The number of fibroblasts and the volume of extracellular fibers were larger than control values by 44% and 31% in the exposed group, but these changes were not statistically significant. Centriacinar changes due to exposure to long term, high ambient ozone in bonnet monkeys results in narrowing of respiratory bronchioles primarily by peribronchiolar inflammation (inflammatory cells, fibers, amorphous matrix) and secondarily through hyperplasia of cuboidal bronchiolar cells. PMID- 4029096 TI - A mathematical model for the transport and fate of organic chemicals in unsaturated/saturated soils. AB - A mathematical model, simulating the transport and fate of nonionizable organic compounds in unsaturated/saturated porous media (soils) in a terrestrial microcosm has been developed. Using the principles of water mass, momentum, heat energy and chemical mass balance, the three fields: moisture, temperature, and liquid phase chemical concentration are solved for simultaneously by coupling the soil slab to an environmentally realistic air-soil interface (a dynamic free boundary) conditions and a prescribed height water table. The environmental conditions at the soil surface-air chamber interface are easily changed, via geometric scaling factors, to simulate either an open agricultural field or a landfill type of situation. Illustrative simulation runs examine the effects of different soil-chemical characteristics on hydrological and chemical concentration profiles. PMID- 4029097 TI - Effects of polyhalogenated aromatic compounds on porphyrin metabolism. AB - Heme production is a vital metabolic process that occurs in the bone marrow and liver. Porphyrins are unused by-products of this biosynthetic process and normally occur in urine and other body fluids in low concentrations. Various disorders can disrupt the heme biosynthetic process, causing greater quantities of porphyrins in urine. The porphyrias are a group of diseases characterized by excessive porphyrins and other precursors in urine. Porphyrias may be either hereditary or acquired through exposure to certain drugs or chemicals. Porphyria cutanea tarda (PCT) is the disease associated with exposure to polyhalogenated aromatic compounds. The urinary porphyrin pattern is of great value in diagnosing PCT and defining the etiology of the disease. As this liver disease from chemical damage develops, the urinary pattern progressively changes. With the development of a rapid and sensitive high-performance liquid chromatography analysis, urinary porphyrin patterns can be easily monitored. All free porphyrin acids can be quantitatively analyzed in less than 15 min. In our studies of groups exposed to porphyrinogenic chemicals, we have not observed clear differences in the urinary porphyrin patterns of cases when compared with carefully selected controls. In animal studies, however, PCT was clearly associated with polybrominated biphenyl exposure. Future evaluation of the utility of urinary porphyrin patterns as a diagnostic tool will require a cohort that has received a recent, well-documented exposure and a comparable control population. Assay of erythrocyte uroporphyrinogen decarboxylase activity will also be needed to define the form of the PCT. PMID- 4029098 TI - Urinary D-glucaric acid excretion in the Seveso area, polluted by tetrachloro dibenzo-p-dioxin (TCDD): five years of experience. AB - On July 10, 1976, an explosion in a factory in Seveso, Italy, located 30 km north of Milan, producing trichlorophenol caused the release of TCDD-containing compounds in the surrounding area. Since extremely small doses of TCDD have been shown to induce hepatic microsomal enzymes in animals, urinary D-glucaric acid excretion (a measurable index of enzyme induction), has been investigated in Seveso in adults and children 6 to 8 years old, in order to clarify whether levels of environmental exposure to TCDD were sufficient to produce an induction in man. Urine samples were collected from 1976 to 1981. As a control group, people living in Cannero (a nonindustrialized village on lake Magiore), in Busto Arsizio (a small industrial town near Milan) and in Lentate (a noncontaminated zone near Seveso) were chosen. In the first period of collection, children with chloracne (which is considered to be a characteristic manifestation of intoxication with chlorinated products) showed significantly increased levels of D-glucaric acid excretion compared to children without chloracne living in the same zone. As far as chronic exposure is concerned, up to 3 years after the accident both adults and children living in the Seveso area showed a statistically significant enhancement of D-glucaric acid elimination compared to the control groups. This study demonstrates that adults and children living in the polluted zones had an increased activity of hepatic microsomal enzymes for some years, since, although the urinary excretion of D-glucaric acid is only an indirect measure of enzyme activity, studies in man have indicated that it is, however, sensitive and quantitative.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4029100 TI - U.S. cancer mortality 1950-1978: a strategy for analyzing spatial and temporal patterns. AB - There are a number of technical and statistical problems in monitoring the temporal and spatial variation of local area death rates in the United States for evidence of systematically elevated risks. An analytic strategy is proposed to reduce one of the major statistical concerns, i.e., that of identifying areas with truly elevated mortality risks from a large number of local area comparisons. This analytic strategy involves two stages. The first is a procedure for examining the entire distribution of local area death rates instead of simply selecting high risk "outliers." The second is the development of an analytic procedure to relate the temporal changes in the cross-sectional distribution of local area death rates to models of the disease process operating within the populations in those areas. The procedures are applied to data on cancer mortality for the 3050 counties (or county equivalents) of the United States over the period 1950 to 1978. A number of striking mortality patterns, both within the entire United States and within various regions and states, are identified. For example, perhaps the most persistent finding was that the risk increases in the death rates for respiratory cancer mortality were due to a "catching up" of nonmetropolitan county mortality rates with metropolitan area mortality rates. PMID- 4029099 TI - Assessment of human exposure to polychlorinated dibenzofurans and dioxins. AB - Fires, explosions and other accidents in polychlorinated biphenyl (PCB)-filled equipment can result in possible exposure of firemen, cleaning personnel and regular workers. Inhalation, dermal exposure and ingestion are the possible routes of exposure. An indirect assessment of the exposure can be made by analyses of wipes, air and water samples and clothes. A direct assessment of exposure can be made by analyses of blood samples, adipose and other tissue samples, feces and bile. PMID- 4029101 TI - Mutagenic efficiency of organophosphorus insecticides used in combined treatments. AB - Male mice (Q strain) received two consecutive injections of organophosphorus insecticides: a phosphonate (trichlorfon) was combined to a thiophosphate (methylparathion) or a dithiophosphate (malathion or methylazinphos) in order to evaluate the interactions at the genetic and cytogenetic levels. No increase in chromosome damage was observed in bone marrow cells, spermatogonia, and primary spermatocytes. In a dominant lethal mutation assay, the frequency of postimplantation lethality was not significantly increased over the control level. The percentage of preimplantation losses was enhanced, probably due to a toxic effect on male germ cells. PMID- 4029102 TI - Measurement of nicotine in building air as an indicator of tobacco smoke levels. AB - Humans apparently differ greatly in their sensitivity and tolerance to tobacco smoke, thereby creating conflicts in the workplace. Resolution of conflicts in a large office complex at the authors' institution required an objective measure of smoke levels. A gas chromatographic technique was devised for collection and analysis of nicotine concentrations in the building air as an indicator of tobacco smoke pollution. Segregation of smokers and nonsmokers in the large office complex still resulted in substantial exposure of the nonsmoker to tobacco smoke, although a gradient of exposure was certainly observed. Passive tobacco smoke consumption in the smoking area of the office complex was calculated to be equivalent to 1.1 cigarettes per 8-hr period, and nicotine density in this area was 1.96 microgram/m. The restriction of smoking to a foyer area outside the office complex resulted in a slow but eventual reduction in nicotine concentrations in the office complex. Observed "background" nicotine concentration levels corresponding to 4 to 7% of those encountered in smoking areas demonstrate that central air circulation systems and people movement increase the nicotine level throughout all rooms of a building, regardless of the smoking policies of an individual office complex. Recent documentation of the relationship between passive smoking and cancer, heart disease, pulmonary dysfunction, and allergic responses argues for restriction of smoking to building exteriors. PMID- 4029104 TI - Personality factors associated with anticipatory nausea/vomiting in patients receiving cancer chemotherapy. AB - One hundred cancer chemotherapy patients rated the severity of pre- and posttreatment nausea and emesis and completed the State-Trait Anxiety Inventory. In addition, scores on the Millon Behavioral Health Inventory were obtained for 59 of those patients. Thirty-three percent of the patients reported having experienced anticipatory nausea and 11% reported having experienced anticipatory vomiting. Patients who experienced anticipatory nausea had more posttreatment nausea and vomiting, were more depressed, and were characteristically more anxious than other patients. A personality profile including the future despair, social alienation, and inhibited style (from the Millon Behavioral Health Inventory) identified patients with anticipatory nausea. PMID- 4029103 TI - Interaction of alkylmercuric compounds with sodium selenite. II. Metabolism of methylmercuric chloride administered alone and in combination with sodium selenite in rats. AB - Repeated doses of sodium selenite (Se) were administered to rats receiving repeated (IV or PO) doses of 0.25 or 2.5 mg Hg/kg methylmercuric chloride (Me2(203)Hg). Se (0.5 mg/kg) was observed to alter the distribution of Me203Hg among tissues as well as among subcellular fractions of kidneys and liver. An excess of selenium resulted in a twofold decrease in the mercury content of kidneys and a similar increase in the mercury content of brain. PMID- 4029105 TI - "I can tell when my blood pressure is up, can't I?". AB - Forty-four insurance company employees were measured on blood pressure, moods, symptoms, and predictions of their blood pressures, twice daily for 10 days. Twenty subjects had elevated blood pressure and 24 did not. The measures were correlated within-subjects to determine if blood pressure predictions were associated with moods, symptoms, or blood pressure readings, and if moods and symptoms were related to blood pressure. Predictions of pressure were expected to be correlated with symptoms and moods, but not with blood pressure. No strong relationship was expected when blood pressure was compared to symptoms or to moods. The data showed that self-predictions of blood pressure were most strongly associated with reported symptoms, next with reported moods, and least with actual blood pressure. A comparison of subjects who were accurate in predicting their blood pressure with those who were not showed no differences in blood pressure levels, systolic blood pressure variation, self-esteem, or private body consciousness. Subjects' beliefs that they could monitor blood pressure were little influenced by contrary information. The results suggest it would be an error to encourage subjects to believe they can successfully treat blood pressure elevations by monitoring symptoms related to blood pressure change. PMID- 4029106 TI - Optimism, coping, and health: assessment and implications of generalized outcome expectancies. AB - This article describes a scale measuring dispositional optimism, defined in terms of generalized outcome expectancies. Two preliminary studies assessed the scale's psychometric properties and its relationships with several other instruments. The scale was then used in a longitudinal study of symptom reporting among a group of undergraduates. Specifically, respondents were asked to complete three questionnaires 4 weeks before the end of a semester. Included in the questionnaire battery was the measure of optimism, a measure of private self consciousness, and a 39-item physical symptom checklist. Subjects completed the same set of questionnaires again on the last day of class. Consistent with predictions, subjects who initially reported being highly optimistic were subsequently less likely to report being bothered by symptoms (even after correcting for initial symptom-report levels) than were subjects who initially reported being less optimistic. This effect tended to be stronger among persons high in private self-consciousness than among those lower in private self consciousness. Discussion centers on other health related applications of the optimism scale, and the relationships between our theoretical orientation and several related theories. PMID- 4029108 TI - Productivity and health of Japanese workers--past, present and future. PMID- 4029107 TI - The relative efficacy of avoidant and nonavoidant coping strategies: a meta analysis. AB - A casual review of the research literature on coping strategies suggests that strategies involving avoidant tactics are effective in reducing pain, stress, and anxiety in some cases, whereas nonavoidant strategies (called here attention), appear to be more effective in others. This article reports the results of a series of meta-analyses to ascertain whether there are systematic patterns in the empirical literature that describe when attention strategies are more or less effective than avoidant strategies. In particular, we consider the role of different kinds of attentional sets and also the role of time--whether some kinds of strategies work best in the early phases of the stress experience, and others are more efficacious in later phases of the stress experience. Results of an overall analysis of studies providing tests of attention versus avoidance indicated little evidence for one strategy's superiority. However, supplementary analyses, motivated by theoretical reasons, suggest there are boundary conditions that define the relative efficacy of a specific strategy. Overall, avoidance was associated with more positive adaptation in the short-run. However, attention was superior to avoidance if the former involved a focus on sensory schemata rather than emotional processing. If attention involved an emotional interpretational set or no explicit set, then it was associated with more negative outcomes than avoidance. In terms of long-term outcomes, avoidance indicates better outcomes initially, but with time, attention was associated with more positive outcomes. A final set of analyses found that both attention and avoidance facilitate adaptation as compared with no instruction controls. The meta-analyses suggest the important role of interpretational set and whether one looks at the immediate or at the long-term effects of coping. Limitations of the analyses and directions for future research are discussed. PMID- 4029109 TI - Hazard analysis in chemical complexes in Japan--especially those caused by human errors. PMID- 4029110 TI - Measurement of ability of older workers. PMID- 4029111 TI - A study of VDU operators' information processing based on saccadic eye movement and response time. PMID- 4029112 TI - Visual effects of wall colours in living rooms. PMID- 4029113 TI - A kinesiologic study of erectores spinae activity during trunk flexion and extension. PMID- 4029114 TI - Feedback control of the level of arousal using skin potential level as an index. PMID- 4029115 TI - Evaluation of upper-limb function by the sensor pegboard test method. PMID- 4029116 TI - Differential modulation of the expression of axonal proteins by non-neuronal cells of the peripheral and central nervous system. AB - Axonal behavior during the formation of the neuronal network of the nervous system has been shown to be under environmental control. Hence, as a first step in a project aiming to elucidate the molecular basis of axonal functions, we have identified axonal proteins whose synthesis is subject to environmentally induced changes. Neurons from chicken embryonic dorsal root ganglia (DRG) were grown in a compartmental cell culture system that allows selective examination of axonal proteins. Non-neuronal cells of the peripheral or central nervous system were co cultured with the DRG axons. The axonal proteins expressed under these different environmental conditions were examined by metabolic labeling and two-dimensional SDS-polyacrylamide gel electrophoresis. Computerized quantification revealed that 12 out of 400 axonal proteins responded to changes in the local axonal environment by a change in their relative abundance. Some proteins changed in response to both types of co-cultures whereas some changed specifically under the influence of either peripheral or central non-neuronal cells. PMID- 4029117 TI - A new member of the prolactin-growth hormone gene family expressed in mouse placenta. AB - Mouse placenta has been found to contain an mRNA that encodes a previously unidentified member of the prolactin-growth hormone family. This 1.1-kb mRNA (designated PRP mRNA) was detected as a cDNA clone that hydridized to a cDNA clone of mouse proliferin, a recently described growth-associated placental protein related to prolactin. PRP mRNA levels are highest in the fetal part of the placenta and peak at day 12 of gestation, decreasing gradually until term. The 972-bp sequence of PRP mRNA, determined from two cDNA clones, encodes a protein of 244 amino acid residues that has a hydrophobic leader sequence. The protein encoded by PRP mRNA has significant homology to all of the members of the prolactin family, yet is different from each of them; it also differs from mouse placental lactogen. Nucleotide sequence homology is most extensive between PRP and proliferin mRNAs, particularly at their 5' ends, where they share 92 of the first 97 nucleotides. PMID- 4029118 TI - Sequencing of the chicken non-erythroid spectrin cDNA reveals an internal repetitive structure homologous to the human erythrocyte spectrin. AB - Immunological screening of a chicken gizzard cDNA expression library was used to isolate two clones encoding a part of the non-erythroid spectrin-like protein. Clones were identified by immunoblotting of the polypeptides synthesized in Escherichia coli cells transformed with cDNA cloned in the pUC8 plasmid vector using polyclonal rabbit antibodies raised against bovine non-erythroid spectrin. The sequence of an approximately 1.5-kb cDNA insert of one clone was determined. Analysis of the predicted amino acid sequence reveals that, despite differences in immunological cross-reactivity and peptide maps, the chicken non-erythroid and the human erythrocyte spectrins are highly homologous proteins. Like the human erythrocyte spectrin, the chicken smooth muscle spectrin appears also to be constructed from repeated, homologous structures of 106 amino acid residues. This is probably a universal structure motif of spectrins. PMID- 4029119 TI - Gene duplications in the TL region of the mouse major histocompatibility complex. AB - We have isolated a class I gene from the TL region of the A/J mouse. The gene, T2A, is a homologue of the C57BL/10 mouse gene T2. In the process of mapping this gene we screened a number of BALB/c class I cosmid clusters with a T2A flanking probe. Several of the hybridizing clusters were found to contain identical DNA segments and could therefore be linked together into one single BALB/c TL region which appears to be identical to the TL region of the C57BL/10 mouse. However, two of the hybridizing clusters do not overlap with the C57BL/10 TL region. It appears that these two clusters represent a partial duplication of the TL region in the BALB/c mouse. PMID- 4029120 TI - Differential methylation of the c-H-ras gene in normal mouse cells and during skin tumour progression. AB - We have previously shown that the mouse c-H-ras gene acquires transforming activity in chemically induced skin tumours. We have now investigated the pattern of DNA methylation at HpaII and XhoI sites around the c-H-ras locus in various tissues and stages of epidermal tumour progression. The results of this study suggest a correlation between the methylation state of the c-H-ras gene and its susceptibility to oncogenic conversion by a point-mutation. The locus is substantially undermethylated in normal epidermis in comparison with NIH/3T3 fibroblasts. Intermediate levels of methylation were observed in the other tissues investigated. The undermethylation at HpaII sites in epidermal DNA persists through the morphologically distinct phases of hyperplasia, benign papilloma and malignant carcinoma. Methylation at a specific XhoI site close to the c-H-ras gene is significantly reduced with respect to normal epidermis in some, but not all epidermal tumours. The methylation state of the c-H-ras locus in specific tumours is stably maintained following transfection of these DNAs into NIH/3T3 cells and selection of transformed foci. Demethylation of the locus is not essential in vitro for the transforming activity of DNA from epidermal tumours. The significance of changes in the methylation pattern of the c-H-ras gene in different tissues and during tumour progression is discussed. PMID- 4029121 TI - Tumor promoter phorbol-12-myristate-13-acetate induces poly(ADP)-ribosylation in fibroblasts. AB - The tumor promoter phorbol-12-myristate-13-acetate (PMA) causes an increase in pol(ADP)-ribosylation in mouse and human fibroblasts via the intermediate formation of active oxygen. In contrast to poly(ADP)-ribosylation induced by the methylating agent N-methyl-N'-nitro-N-nitrosoguanidine, de novo RNA and protein synthesis are required and the accumulation of the polymer occurs in the absence of detectable DNA strand breakage. Our results suggest a mechanism for PMA induced modulation of chromatin structure and gene expression. PMID- 4029123 TI - Sequence-specific trans-activation of the adenovirus EIIa early promoter by the viral EIV transcription unit. AB - The contribution of adenovirus early genes, other than that of the well documented EIa immediate early gene, to the transcriptional regulation of the viral EIIa early transcription unit was examined. HeLa cells were transfected with EIIa-containing plasmids and co-transfected with distinct plasmids bearing one of the viral regions EIa, EIII or EIV. Co-transfection with the EIV recombinants, but not the EIII constructs, stimulated specific transcription from the major EIIaE start site (EIIaE1) by 5- to 15-fold, as concluded from quantitative S1 nuclease analysis of cytoplasmic RNA and in vitro nuclear 'run on' transcription assays. The extent of the EIV-induced stimulation was similar to that achieved by EIa under identical conditions. However, in contrast to our observations for EIa-mediated stimulation, where no unique EIIaE1 promoter elements were implicated, maximal induction by EIV requires sequences between positions -48 and -19 (with respect to the EIIaE1 start site). PMID- 4029122 TI - Transcription of woodchuck hepatitis virus in the chronically infected liver. AB - The transcription of woodchuck hepatitis virus (WHV) genome was studied in the liver of chronically infected woodchucks by Northern blot, nuclease mapping and primer extension analysis. Two major transcripts, 2.1 and 3.7 kb in length, and several minor transcripts were found in samples which supported active WHV replication. The 2.1-kb RNA represents the major transcript of the S gene, encoding the viral surface antigen (WHsAg) as demonstrated by blot-hybridization experiments. Two transcription initiation sites were localized downstream of the second AUG of the pre-S region, 139 and 152 nucleotides upstream of the translation initiation codon of the S gene. The 3.7-kb transcript, present in an equal amount, is slightly larger than the WHV genome and could be involved in the expression of all viral proteins. The data derived from RNA mapping strongly suggest that this transcript is initiated approximately 70 nucleotides upstream of the C gene, encoding the viral core antigen (WHcAg), and represents the message for WHcAg. It might also serve in the viral replication cycle as a potential template for reverse transcription. All WHV-specific transcripts were found to be processed at a unique site, 20 nucleotides downstream of the polyadenylation signal situated within the core gene. A different set of WHV specific mRNAs was observed in a woodchuck hepatocellular carcinoma when only integrated forms of WHV DNA could be detected. Two RNA species of 2.3 and 4.6 kb were characterized. The 3.7-kb RNA was absent, reinforcing the hypothesis that this transcript corresponds to the pre-genome. PMID- 4029124 TI - Progenitor cells from embryonic chick dorsal root ganglia differentiate in vitro to neurons: biochemical and electrophysiological evidence. AB - We have analyzed the appearance of neurons and glial cells in chick dorsal root ganglia during development. Neurons were identified by the presence of polysialogangliosides recognized by tetanus toxin (GD1b, GT1) or by the monoclonal antibody Q211 directed against polysialogangliosides containing four, five and six sialic acid residues. Glial cells were identified by the presence of 04 antigen. A population of undifferentiated cells, i.e., cells which express neither neuronal nor glial cell surface antigens, present in dorsal root ganglia until embryonic day 7, was separated from the neuronal and glial population. This cell population contains neuronal progenitor cells which differentiate to neurons within 1 day in culture. This differentiation process is characterized by the appearance of neuronal morphology, of neuron-specific gangliosides and by the appearance of voltage-dependent sodium and calcium channels. PMID- 4029125 TI - Extensive DNA sequence homologies between the human Y and the long arm of the X chromosome. AB - It has been proposed that sequence homology should exist between the short arms of the human sex chromosomes, in the regions pairing at meiosis. Out of 40 clones picked at random from a collection of non-repetitive DNA sequences derived from the human Y chromosome, we have found nine sequences which show very high homology with sequences located on the X chromosome. All nine probes originate from the euchromatic part of the Y chromosome. All the homologous sequences are located within the Xq12-Xq22-24 region. None of them map to the short arm of the X chromosome. We conclude that an important part of the euchromatic region of the Y chromosome is homologous to the middle of the X chromosome long arm, possibly as a result of recent translation event(s). PMID- 4029126 TI - Quantitation of the EEG and pharmacodynamic modelling of hypnotic drugs: etomidate as an example. AB - Six volunteers were subjected to an infusion of etomidate designed to generate linearly increasing plasma concentrations with a slope of 0.05 microgram ml-1 min 1. Cessation of infusion was determined by the occurrence of burst suppression patterns on the EEG. Infusion was restarted when the volunteers recovered personal and temporal orientation. This cycle was repeated twice. The drug input function, the pharmacokinetic parameters of etomidate as derived from a 'least squares' fit, and the median EEG frequency were used to establish a pharmacological model of etomidate. Two modelling procedures, the pharmacokinetic pharmacodynamic, and the input-output modelling procedure, are compared. These procedures yield different results with respect to the kinetic data. As one possible explanation, a different pharmacokinetic behaviour of etomidate in the venous blood and at the site of drug action is discussed. PMID- 4029127 TI - Infusion strategies to investigate the pharmacokinetics and pharmacodynamics of hypnotic drugs: etomidate as an example. AB - Etomidate was administered to six healthy volunteers by microprocessor controlled infusions, to generate three cycles of linearly increasing plasma levels, with an anticipated slope of 0.05 microgram ml-1 min-1. The infusions were stopped when a deep hypnotic state was obtained, as indicated by burst suppressions in the EEG. The infusions were restarted when the volunteers were fully orientated to person, place and time. The mean (+/-SD) doses of etomidate delivered by the first, second and third infusion were 165 +/- 30, 137 +/- 25 and 157 +/- 26 mg, respectively. Certain clinical signs were observed and related to the plasma concentrations of etomidate. Pharmacokinetic analysis was undertaken using an open two-compartment model. The therapeutic window was in a range of plasma concentrations between 0.3 and 1.0 microgram ml-1 of etomidate. Pharmacokinetic analysis gave a volume for the central compartment of 50 +/- 11 litre, an apparent volume of distribution of 252 +/- 51 litre and a total clearance of 1693 +/- 504 ml min-1. Microprocessor controlled infusions can serve as a powerful tool for research in clinical pharmacology. The achievement of linearly increasing plasma levels of etomidate allowed further pharmacokinetic and pharmacodynamic modelling concepts to be realized. PMID- 4029128 TI - The effect of dopamine on muscle PO2 in healthy volunteers and intensive care patients. AB - The effect of systemic dopamine administration (2-10 micrograms kg-1 min-1) on the Po2 distribution (histograms) and the mean Po2 in the m. vastus lateralis of m. quadriceps femoris in nine healthy volunteers and seven critically ill patients has been studied with a newly developed bedside measuring procedure. Dopamine initially raised mean muscular Po2 in both groups. In the volunteers, mean muscular Po2 thereafter decreased gradually but still remained slightly elevated after 30 min of dopamine infusion. This increase in muscle oxygenation could be abolished by the administration of a dopamine antagonist (metoclopramide). In the patients, the initial dopamine-induced increase of Po2 was significantly slower and reached a plateau within 30 min. The results are discussed with special attention given to the data available on the action of dopamine on given peripheral circulation. PMID- 4029129 TI - Biosynthesis and in vitro translation of type IV procollagens. AB - The present paper describes how epithelial cells, cultured from bovine anterior lens capsule explants, synthesize and secrete procollagen type IV polypeptide chains alpha 1(IV) and alpha 2(IV). Metabolic labeling of these cells with [14C]proline for different time intervals and subsequent analysis by SDS/polyacrylamide gel electrophoresis revealed the presence of two polypeptide chains with apparent molecular masses of 180 kDa and 170 kDa. The procollagens were bacterial-collagenase-sensitive and were specifically immunoprecipitated by antibodies raised against the 7S domain of type IV collagen. Type IV procollagen poly(A)-rich RNA was isolated from cultured lens capsule cells and translated in a reticulocyte lysate cell-free system. Two polypeptides with apparent molecular masses of 152 kDa and 145 kDa were identified as procollagen type IV unmodified chains by gel electrophoresis, collagenase digestion and specific immunoprecipitation. During experiments in which cells were labeled in the presence of alpha, alpha'-bipyridyl, type IV procollagen appeared as one major band comigrating with a 145 kDa polypeptide on SDS-gel electrophoresis. PMID- 4029130 TI - Structures of shorthorn sculpin antifreeze polypeptides. AB - The amino acid sequences of the two major antifreeze polypeptides (AFP) from the shorthorn sculpin have been determined using an automatic protein sequencer and enzymic digestion. These two polypeptides, SS-3 and SS-8, consist of 33 and 45 amino acid residues respectively. The N-terminal methionyl residue is blocked in both the polypeptides. When aligned for maximum structural similarity these two AFP are 80% homologous, and there appears a deletion of 12 amino acid residues at the N-terminal portion of SS-3. Like the winter flounder AFP, both the sculpin AFP also contain the 11-amino-acid repeat sequences. The secondary structure of the sculpin AFP is mainly alpha-helical as deduced from circular dichroic spectral data. The helical content of SS-8 is high (73%), while that of SS-3 is moderate (about 45%). The latter exhibits a relatively weak antifreeze activity. Removal of the blocked N-terminal residue in SS-8 did not alter the helical content significantly but did reduce the antifreeze activity. Helical contents of proteolytically generated fragments of AFP are much lower, and they are devoid of activity. The alpha-helix in the SS-8 component is seen to be amphiphilic in character. The relevance of this feature to the mechanism of the antifreeze action is briefly discussed. PMID- 4029131 TI - Solution conformation of the C-terminal domain of skeletal troponin C. Cation, trifluoperazine and troponin I binding effects. AB - Proton magnetic resonance spectroscopy has been used to study the cation (Mg2+, Ca2+)-dependent conformational states of the C-terminal domain of rabbit skeletal troponin C under a variety of solution conditions. Nuclear Overhauser data and paramagnetic probe observations provide definition of the configuration of this region of troponin C. Comparative study of homologous proteins identify common features of the tertiary structure relevant to the cation binding reaction. Complex formation with troponin I and the drug trifluoperazine is observed to adjust the solution conformation of the C-terminal domain of troponin C. The interactive conformational response to cation coordination and the binding of the drug and troponin I are discussed. PMID- 4029132 TI - Synthesis of poly(ethylene glycol)-bound NADP by selective modification at the 6 amino group of NADP. AB - The N-1 position of the adenine ring of NADP was selectively alkylated by the reaction of 2',3'-cyclic NADP with 3-propiolactone to yield 2',3'-cyclic 1-(2 carboxyethyl)-NADP (I). Derivative I was converted to a mixture of the isomers of N6-(2-carboxyethyl)-NADP with their phosphate groups at the 2' or 3' position (IIa and IIb) by chemical reduction, alkaline rearrangement and chemical reoxidation. Carbodiimide coupling of the mixture of IIa and IIb to alpha, omega diaminopoly(ethylene glycol) gave the 2', 3'-cyclic derivative of poly(ethylene glycol)-bound NADP (III), which was enzymically hydrolyzed to yield poly(ethylene glycol)-bound NADP (PEG-NADP). PEG-NADP has good cofactor activity (16-100% of that of NADP) for NADP-specific and NAD(P)-specific dehydrogenases except isocitrate and glucose dehydrogenases. For NAD-specific enzymes, PEG-NADP has higher cofactor activity than NADP: for horse liver alcohol dehydrogenase, the cofactor activity of PEG-NADP is 40 times that of NADP and 14% of that of NAD. Kinetic studies show that for most of enzymes tested, Km values for PEG-NADP are larger than those for NADP and V values for PEG-NADP are similar to those for NADP. PEG-NADP proved to be applicable in a continuous enzyme reactor, in which reactions of glutamate dehydrogenase and glucose-6-phosphate dehydrogenase were coupled by the recycling of PEG-NADP. PMID- 4029133 TI - Carbon-13 and nitrogen-15 nuclear-magnetic-resonance investigation on Desulfovibrio vulgaris flavodoxin. AB - Desulfovibrio vulgaris apoflavodoxin has been reconstituted with 15N and 13C enriched riboflavin 5'-phosphate. For the first time all carbon atoms of the isoalloxazine ring of the protein-bound prosthetic group have been investigated. The reconstituted protein was studied in the oxidized and in the two-electron reduced state. The results are interpreted in terms of specific interactions between the apoprotein and the prosthetic group, and the chemical structure of protein-bound FMN. In the oxidized state weak hydrogen bonds exist between the apoprotein and the N(5), N(3) and O(4 alpha) atoms of FMN. The N(1) and O(2 alpha) atoms of FMN form strong hydrogen bonds. The isoalloxazine ring of FMN is strongly polarized and the N(10) atom shows an increased sp2 hybridisation compared to that of free FMN in aqueous solution. The N(3)-H group is not accessible to bulk solvent, as deduced from the coupling constant of the N(3)-H group. In the reduced state the hydrogen bond pattern is similar to that in the oxidized state and in addition a strong hydrogen bond is observed between the N(5)-H group of FMN and the apoprotein. The reduced prosthetic group possesses a coplanar structure and is ionized. The N(3)-H and N(5)-H groups are not accessible to solvent water. Two-electron reduction of the protein leads to a large electron density increase in the benzene subnucleus of bound FMN compared to that in free FMN. The results are discussed in relation to the published crystallographic data on the protein. PMID- 4029134 TI - Identification and characterization of the principal proteins of the fat-globule membrane from guinea-pig milk. AB - The milk-fat-globule membrane (MFGM) was isolated from guinea-pig milk and the membrane-associated proteins and glycoproteins characterized by electrophoretic techniques. Major components of the membrane included PAS-I, a sialoglycoprotein of Mr greater than or equal to 200000, the redox enzyme xanthine oxidase and the glycoprotein, butyrophilin. Membrane preparations also contained two other glycoproteins, GP-80 and GP-55, of Mr 80000 and 55000, respectively. Comparison of guinea-pig xanthine oxidase and butyrophilin with proteins from bovine MFGM by peptide mapping procedures, showed that the two proteins in both species were similar, but not identical. GP-55 may also be related to glycoproteins of Mr 45000 and 48000 in the bovine membrane. The integral and peripheral components of guinea-pig MFGM were identified by treating membrane preparations with sodium carbonate solutions at high pH and by partitioning the membrane proteins in solutions of Triton X-114. By these criteria xanthine oxidase and GP-55 appeared to be peripheral components and GP-80 an integral protein of the membrane. PAS-I and butyrophilin displayed hydrophilic properties in Triton X-114 solutions, but could not be removed from membrane preparations with sodium carbonate. Possible reasons for these ambiguous data are discussed. The observed similarity between several of the proteins of guinea-pig and bovine MFGM implies that these proteins may have specific functions related to milk secretion in mammary tissue, e.g. in the budding of milk-fat globules or the exocytosis of milk protein and lactose at the apical surface. PMID- 4029135 TI - Scatter analysis of discrete-sized chromatin fragments favours a cylindrical organization. AB - Fragments of chromatin containing 23 +/- 2.5 nucleosomes have been fractionated after light nuclease treatment of chicken erythrocyte nuclei. Low-angle scattering measures the total z-average radius of gyration of the already well defined particles and the shape of scatter curves can be compared with three dimensional analysis as opposed to cross-section analysis of long chromatin fragments. The data show that the particles are not spherical, have no detectable hole in the center of the structure and are best represented by a solid rod-like shape such as that generated by a coil of nucleosomes with the centre perhaps filled with linker DNA and histone H1/H5. 23 nucleosome fragments, where the DNA is partially fragmented, have near-identical scatter curves to the above-defined intact particles, indicating the primary importance of histone proteins in maintaining the integrity of the chromatin higher-order structure. Neutron scattering shows the radii of gyration to be contrast-independent, which fits in with the model calculations for solenoids. Particles with fragmented DNA and the intact particles, therefore, behave as sections of a solenoidal higher-order structure and possibly are observed as "superbeads' only during the folding and unfolding pathways of nucleosome multimers. PMID- 4029136 TI - Long-term effects of physiological oxygen concentrations on glycolysis and gluconeogenesis in hepatocyte cultures. AB - Primary cultures of adult rat hepatocytes were kept for 46 h with either insulin ('insulin cells') or glucagon ('glucagon cells') as the dominant hormone under different oxygen concentrations with 13% (v/v) O2 mimicking arterial and 4% hepatovenous levels. Thereafter metabolic rates were measured for a 2 h period under the same ('overall long-term O2 effects') or a different ('short-term O2 effects') oxygen concentration. From the differences of the two effects the 'intrinsic long-term O2 effects' were derived. Glycolysis, as measured in 'insulin-cells', was stimulated by low O2 levels. It was about threefold faster in cells cultured and tested under 4% O2 as compared to cells cultured and tested under 13% O2, indicating the overall long-term effect. Glycolysis was about twofold faster in cells cultured and tested under 4% O2 as compared to cells cultured under 4% O2 but tested under 13% O2, demonstrating the short-term effect. Glycolysis was about 1.5-fold faster in cells cultured and tested under 4% O2 as compared to cells cultured under 13% O2 but tested under 4% O2, showing the intrinsic long-term effect. This difference was roughly parallel to the difference in levels of glucokinase and pyruvate kinase. Gluconeogenesis, as measured in 'glucagon cells', was stimulated by high O2 levels. Similar to glycolysis overall long-term, short-term and intrinsic long-term effects could be distinguished. The intrinsic long-term effects determined under 13% O2 corresponded to a 1.5-fold stimulation and paralleled the difference in phosphoenolpyruvate carboxykinase levels. The present results show that physiological oxygen concentrations also modulate hepatic carbohydrate metabolism by long-term effects and that the O2 gradient over the liver parenchyma thus contributes to the metabolic differences between periportal and perivenous hepatocytes in vivo. PMID- 4029137 TI - The amino acid sequences of the copper/zinc superoxide dismutases from swordfish and Photobacter leiognathi confirm the predictions made from the compositions. AB - Recent suggestions that the amino acid sequence of the copper/zinc superoxide dismutases of swordfish and Photobacter leiognathi do not support the theory that the bacterium obtained the gene for the enzyme by transfer from its eucaryotic symbiont [Rocha, H. A., Bannister, W. H. and Bannister, J. V. (1984) Eur. J. Biochem. 145, 477-484] are examined. The amount of difference between the sequence is in good agreement with expectation from the amino acid compositions. Moreover, the gene-transfer hypothesis cannot be discarded without postulating an enormous increase in the rate at which the superoxide dismutase gene has accumulated amino acid substitutions since the divergence of the swordfish and cattle lineages. PMID- 4029138 TI - Temperature-induced conformational transition in rabbit muscle aldolase studied by temperature dependence of sulfhydryl reactivity. AB - A temperature-induced non-denaturing conformational transition in rabbit muscle aldolase has been as subject of discussion and controversy for some period of time. In this study the temperature dependence of the reactivity of aldolase SH groups is investigated in order to detect subtle changes in the enzyme conformation. For model thiol-containing systems such as cysteine, glutathione and bovine serum albumin, linear Arrhenius plots have been obtained for the reaction with 5,5'-dithiobis(2-nitrobenzoic acid). On the other hand, for rabbit muscle pyruvate kinase, a protein which undergoes temperature-induced conformational transition, the plot obtained is nonlinear with a break at the temperature (18 degrees C) close to that reported earlier. In the case of aldolase the Arrhenius plots for three slowly reacting SH groups (Cys-72, 289, 338) and a fast reacting group (Cys-239) are nonlinear with a break at about 26 27 degrees C. The fluorescence measurements show that a plot of the fluorescence intensity of tryptophan residues versus temperature exhibits a break at the same temperature. It is shown that the observed conformational change is fully reversible. In the presence of the competitive inhibitor hexitol 1,6 bisphosphate, which is known to protect Cys-72 and Cys-338 from chemical modification, the Arrhenius plot exhibits a break for the fast reacting Cys-239 residue and is linear for the slowly reacting Cys-289. It is found that 0.6 M urea increases the transition temperature for all exposed SH groups of aldolase. The above results show that at several points in the aldolase molecule, including the active-site region, an abrupt change of microenvironments takes place with temperature. The competitive inhibitor protects a portion of aldolase molecule against the thermal transition. PMID- 4029139 TI - Glutamic acid decarboxylase in tubules and glomeruli isolated from rat kidney cortex. AB - 4-Aminobutyric acid (GABA) synthesis was examined in purified glomeruli and tubules of rat kidney cortex that were incubated in the presence of [2,3 3H2]glutamate. The GABA that was formed was separated from glutamate using anion exchange resin, and identified by means of an automatic amino acid analyser. In the renal cortex only the tubules were able to form GABA (35.0 nmol mg-1 h-1); the remaining GABA synthesis found in the glomerular preparations can most probably be attributed to a contamination by cortical tubules (9%), as shown by determination of a known tubular marker enzyme (L-gamma-glutamyltransferase). Hydroxylamine (1 mM) and ethanolamine-O-sulfate (10 mM), well-known inhibitors of cerebral GABA formation and GABA catabolism respectively, inhibited renal tubular GABA formation at 100% and 44% respectively. PMID- 4029140 TI - Lipopolysaccharides from Yersinia pestis. Studies on lipid A of lipopolysaccharides I and II. AB - The chemical structure of the lipid A of lipopolysaccharide I and II from Yersinia pestis, strain EV 40, was studied. It consists of a (1 ---- 6), beta linked D-glucosamine disaccharide which carries two phosphate groups; one phosphate is linked glycosidically with a glucosamine unit, the other one is linked to the non-reducing glucosamine. Various degradation methods combined with 31P nuclear magnetic resonance spectroscopy showed that the ester-bound phosphate group is linked to a 4-aminoarabinosyl residue and the glycosidically linked phosphate group is linked to a D-arabinofuranosyl residue in lipopolysaccharide II and to the phosphorylethanolamine in lipopolysaccharide I. The hydroxyl groups of the disaccharide are acylated by dodecanoic, hexadecenoic, 3 hydroxytetradecanoic and 3-dodecanoyloxytetradecanoic acids. The amino groups of the disaccharide carry 3-hydroxytetradecanoic and 3-dodecanoyloxytetradecanoic acids. In addition smaller amounts of 3-tetradecanoyloxyltetradecanoic and 3 hexadecanoyloxytetradecanoic acids are present in ester linkage. PMID- 4029141 TI - Phosphorylase kinase from chicken gizzard. Partial purification and characterization. AB - Phosphorylase kinase was partially purified (530-970-fold) from chicken gizzard smooth muscle by a procedure involving ammonium sulfate fractionation, chromatography on 8-(6-aminohexyl)adenosine-5'-phosphate--Sepharose 4B and glycerol density gradient ultracentrifugation. The final and most efficient purification step takes advantage of the relatively high molecular mass of gizzard phosphorylase kinase, which was found to be similar to that of rabbit skeletal muscle enzyme. The gizzard kinase, further purified to near homogeneity by calmodulin-Sepharose 4 B affinity chromatography, showed one main protein band of 61 kDa, upon dodecyl sulfate acrylamide gel electrophoresis. Four minor protein bands of higher molecular mass were also present but no protein stain was seen at the position of the gamma subunit. The gizzard phosphorylase kinase showed a high pH 6.8/8.2 activity ratio of 0.53, it was stimulated by Ca2+, inhibited up to 80% by EGTA and it was activated about 1.9-fold by calmodulin. The km value for ATP was 0.45 mM, while the K0.5 for rabbit muscle phosphorylase b was extremely low, more than 200-fold lower than the Km of nonactivated skeletal muscle phosphorylase kinase for its protein substrate. High concentrations of phosphorylase b were found to be inhibitory. At 10 mg/ml phosphorylase b, the maximum activity of the kinase was inhibited fivefold. No evidence has been obtained indicating autophosphorylation or the existence of active and inactive forms of gizzard phosphorylase kinase. Limited proteolysis of the smooth muscle kinase with trypsin was accompanied by a twofold activation at pH 6.8. PMID- 4029143 TI - Effect on lysosomes of invertase endocytosed by rat-liver. AB - The intracellular localization of invertase endocytosed by rat liver was investigated by analytical centrifugation in sucrose and Percoll gradients of mitochondrial fractions originating from rats killed 15 h after injection. After isopycnic centrifugation in a sucrose gradient, invertase is located in higher density zones than acid hydrolases. The difference between the distribution of invertase and that of acid hydrolases increases with the amount of invertase injected. When the invertase dose is sufficiently high, a change of lysosomal enzyme distribution is clearly visible. It consists in the shift of a proportion of these enzymes to higher density regions where invertase is located. The proportion of hydrolase activity affected by invertase is different for each enzyme measured; it is the least pronounced for acid phosphatase, and most for acid deoxyribonuclease and arylsulfatase. A pretreatment of the rat with Triton WR 1339 considerably decreases the equilibrium density of structures bearing invertase. Nevertheless invertase distribution is quite distinct from that of the bulk of lysosomal enzymes that are recovered in lower density zones of the gradient; on the other hand the invertase injection to rats treated with Triton WR 1339 causes a spreading of the acid hydrolase distribution towards higher density zones. The distribution of acid hydrolases and invertase in a Percoll gradient depends on the sucrose concentration of the solvent. It is shifted towards higher densities when the sucrose concentration increases. The phenomenon is more important for invertase. These results are best explained by supposing that invertase accumulates in a distinct population of lysosomes that can be individualized as a result of the density increase they are subjected to by the invertase they accumulate. It is proposed that these lysosomes mainly originate from non-parenchymal cells of the liver. PMID- 4029142 TI - Inhibition of cell wall synthesis and acylation of the penicillin binding proteins during prolonged exposure of growing Streptococcus pneumoniae to benzylpenicillin. AB - Growing cultures of an autolysis-defective pneumococcal mutant were exposed to [3H]benzylpenicillin at various multiples of the minimal inhibitory concentration and incubated until the growth of the cultures was halted. During the process of growth inhibition, we determined the rates and degree of acylation of the five penicillin-binding proteins (PBPs) and the rates of peptidoglycan incorporation, protein synthesis, and turbidity increase. The time required for the onset of the inhibitory effects of benzylpenicillin was inversely related to the concentration of the antibiotic, and inhibition of peptidoglycan incorporation always preceded inhibition of protein synthesis and growth. When cultures first started to show the onset of growth inhibition, the same characteristic fraction of each PBP was in the acylated form in all cases, irrespective of the antibiotic concentration. Apparently, saturation of one or more PBPs with the antibiotic beyond these threshold levels is needed to bring about interference with normal peptidoglycan production and cellular growth. Although it was not possible to correlate the inhibition of cell wall synthesis or cell growth with the degree of acylation (percentage saturation) of any single PBP, there was a correlation between the amount of peptidoglycan synthesized and the actual amount of PBP 2b that was not acylated. In cultures exposed to benzylpenicillin concentrations greater than eight times the minimal inhibitory concentration, the rates of peptidoglycan incorporation underwent a rapid decline when bacterial growth stopped. However, in cultures exposed to lower concentrations of benzylpenicillin (one to six times the minimal inhibitory concentration) peptidoglycan synthesis continued at constant rate for prolonged periods, after the turbidity had ceased to increase. We conclude that inhibition of bacterial growth does not require a complete inhibition or even a major decline in the rate of peptidoglycan incorporation. Rather, inhibition of growth must be caused by an as yet undefined process that stops cell division when the rate of incorporation of peptidoglycan (or synthesis of protein) falls below a critical value. PMID- 4029144 TI - Existence of ternary complexes of procarboxypeptidase A in the pancreas of some ruminant species. AB - The existence of procarboxypeptidase A, in the form of a non-covalent ternary complex containing the apparently inactive serine protease (subunit III), has so far been observed only in the ox pancreas. Evidence, obtained in the present study, shows that a ternary complex of procarboxypeptidase A, with a subunit III highly homologous with that of the bovine complex, is also present in two other ruminant species, sheep and goat. The biological significance of these complex forms of procarboxypeptidase A and the consistently high biosynthesis level of the apparently inactive subunit III in all three ruminant species is still unknown. Yet the synthesis of subunit III is not related to the animal diet since in the horse, which is a non-ruminant herbivorous animal, the procarboxypeptidase A is monomeric. Reassociation assays between either bovine subunits II or III and monomeric as well as binary forms of procarboxypeptidase A from various species show that, unlike subunit II, the recognition site for subunit III is highly conserved in all the procarboxypeptidases A and that bovine subunit II is different from porcine chymotrypsinogen C with regard to association. PMID- 4029145 TI - Reactivation kinetics of diethylphosphoryl acetylcholine esterase. AB - The kinetics of reactivation of diethylphosphorylated acetylcholine esterase by pyridine-2-aldoxime methochloride has been studied using the approach of following the course of the hydrolysis of acetylcholine during the reactivation of the phosphorylated enzyme by the reactivator [Tsou, C.-L. (1965) Acta Biochem. Biophys. Sin. 5, 398-417]. Equations are derived based on the scheme of the formation of a complex between the phosphorylated enzyme and the reactivator and the rate of dissociation of this complex is not necessarily faster than the dephosphorylation and regeneration of the active enzyme. The regenerated enzyme then reacts with the substrate through an acetyl-enzyme intermediate as generally depicted. The equation obtained for product formation during the course of reactivation contains two exponential terms and this is in accord with the experimentally observed biphasic reaction. By making the assumption that the dissociation of the phosphorylated enzyme-reactivator complex is much faster than the dephosphorylation reaction, the above equation can be simplified to a form containing only one exponential term. By following the course of the reactivation reaction with the conventional approach of taking aliquots and assaying for enzyme activity recovery, it would appear likely that one would miss the initial stage of this biphasic reaction. PMID- 4029146 TI - Kinetics of calcium dissociation from calmodulin and its tryptic fragments. A stopped-flow fluorescence study using Quin 2 reveals a two-domain structure. AB - The kinetics of calcium dissociation from bovine testis calmodulin and its tryptic fragments have been studied by fluorescence stopped-flow methods, using the calcium indicator Quin 2. Two distinct rate processes, each corresponding to the release of two calcium ions are resolved for calmodulin at both low and high ionic strength. The effect of 0.1 M KCl is to accelerate the slow process from 9.1 +/- 1.5 s-1 to 24 +/- 6.0 s-1 and to reduce the rate of the fast process from 650 s-1 to 240 +/- 50 s-1 at 25 degrees C. In the presence of 0.1 M KCl it was possible to determine activation parameters for the fast process: delta H# = 41 +/- 5 kJ mol-1 and delta S# = -63 +/- 17 J K-1 mol-1. These values are in good agreement with those obtained by 43Ca NMR. Studies of the tryptic fragments TR1C and TR2C, comprising the N-terminal or C-terminal half of calmodulin, clearly identified Ca2+-binding sites I and II as the low-affinity (rapidly dissociating) sites and sites III and IV as the high-affinity (slowly dissociating) sites. The kinetic properties of the two proteolytic fragments are closely similar to the fast and slowly dissociating sites of native calmodulin, supporting the idea that calmodulin is constructed from two largely independent domains. The presence of the calmodulin antagonist trifluoperazine markedly decreased the Ca2+ dissociation rates from calmodulin. One of the two high-affinity trifluoperazine binding sites was found to be located on the N-terminal half and the other on the C-terminal half of calmodulin. The affinity of the C-terminal site is at least one order of magnitude greater. PMID- 4029147 TI - 'Superpolyamines'. Macrocyclic polyamines induce highly efficient actin polymerization. AB - Macrocyclic polyammonium ions induce much more efficient polymerization of actin than the natural polyamines, behaving thus as 'superpolyamines'. The processes observed display large increases in rate, marked structural dependence, macrocyclic and ditopic binding effects and positive cooperativity. PMID- 4029148 TI - Activation of liver cytosol phosphoenolpyruvate carboxykinase by Ca2+ through intracellular redistribution of Mn2+. AB - Calcium has no known direct effect on phosphoenolpyruvate carboxykinase from rat liver cytosol. However, addition of calcium salts to liver postnuclear supernatant led to an increase in assayable enzyme activity in cytosols. This indicates that mitochondria and microsomes present in postnuclear supernatant can participate in observed enzyme activation. The stimulation of phosphoenolpyruvate carboxykinase was prevented by the manganese complexion 1-(2-pyridylazo)-2 naphthol, was not additive with activation by MnCl2 and was inhibited by La3+, Sr2+ and ruthenium red. These data indicate that manganese and mitochondrial or microsomal calcium carriers participate in the mechanism of indirect calcium effect. Measuring of manganese content in cytosols directly, by atomic absorption spectrometry, has provided evidence that there is a pool of manganese associated with mitochondrial and microsomal fraction of rat liver that can be mobilized to the cytosol by calcium ions. The direct addition of this pool of manganese to the cytosol caused the stimulation of phosphoenolpyruvate carboxykinase activity to the same levels as did calcium ions in the postnuclear supernatant. It is postulated that calcium can effect enzyme activity indirectly by releasing manganese from specific cellular compartments into the cytosol. PMID- 4029149 TI - Effects of ATP and adenosine addition on activity of oxoglutarate dehydrogenase and the concentration of cytoplasmic free Ca2+ in rat hepatocytes. AB - Addition of ATP (100 microM) to hepatocytes from starved rats incubated with 5 mM [1-14C]glutamine caused a stimulation of glucose formation; the magnitude of the concomitant increases in 14CO2 production and glutamine consumption indicate that flux from glutamine to glucose was increased. ATP also caused a simultaneous decrease in the cell content of oxoglutarate; together with the increased flux this is consistent with an activation of oxoglutarate dehydrogenase. In corroboration of this, a stimulation by ATP of gluconeogenesis and a decrease in oxoglutarate was also observed with 5 mM proline as substrate. ATP caused an increase in hepatocyte cytoplasmic free Ca2+ concentration, [Ca2+]c, as indicated by the increase in the fluorescence of cytoplasmically trapped quin2, from a resting value of about 0.2 microM to greater than 1 microM. The mechanism of oxoglutarate dehydrogenase activation may be via an increase in mitochondrial Ca2+ content as a consequence of the increase in [Ca2+]c. The effects of 100 microM adenosine were also investigated. An increase in flux from glutamine to glucose was observed together with a decrease in the cell oxoglutarate, thus indicating that adenosine addition to hepatocytes could also activate oxoglutarate dehydrogenase. The activation by adenosine was less than that produced by ATP. Adenosine caused a small apparent increase in [Ca2+]c to 0.3-0.4 microM; it remains to be established if this effect, which is small relative to that of ATP, is sufficient to elicit the activation of oxoglutarate dehydrogenase: alternative mechanisms may exist. PMID- 4029150 TI - Physical studies by NMR and circular dichroism determining three structurally different domains in Physarum polycephalum histone H1. AB - Combined studies which include, NMR spectroscopy, circular dichroism, amino acid analysis and polyacrylamide gel electrophoresis together show that the protein designated as histone H1 from Physarum polycephalum has many of the features of histone H1 derived from other sources. The molecular masses of the globular peptide and the whole molecule were found to be 9000 +/- 1000 Da and 33000 +/- 3000 Da respectively. NMR melting experiments showed that the half-melt temperature was 53 +/- 1 degree C and the enthalpy of melting was 100 kJ . mol-1. Unusual facets of the molecule are the relatively large numbers of histidine residues (6 or 7) and the mono, di and trimethylation of some of the lysines, the major type of modification being trimethylation of 9 +/- 2 residues. The conditions necessary for structuring Physarum H1 are not the same as the histone H1 from calf thymus. It is suggested that titration of the histidine residues is the most decisive step for the development of tertiary folding of the globular unit. PMID- 4029152 TI - Structural studies of the polysaccharide part of the cell wall lipopolysaccharide from Bacteroides fragilis NCTC 9343. AB - The structure of the polysaccharide part of the lipopolysaccharide from Bacteroides fragilis NCTC 9343 has been determined using sugar and methylation analysis as the principal tools. Phenol--water extraction followed by a phenol- chloroform--light petroleum extraction yielded a lipopolysaccharide suitable for structural analysis. Analysis of sugars using alditol acetates showed that the polysaccharide contained L-rhamnose, D-galactose and D-glucose in the approximate molar ratios of 1:5:1. After weak acid hydrolysis, two polysaccharide fractions were isolated by gel permeation chromatography: PSI and PSII with the sugar molar ratios 1:5:1 and 1:2:1 respectively. Chromium trioxide oxidation revealed that all galactosyl residues have the beta configuration, and that the rhamnosyl and glucosyl residues have the alpha configuration. From methylation analysis of lipopolysaccharide and the PS I and PS II fractions the following structures could be deduced. PMID- 4029151 TI - Primary structure of two major glycans of bovine fibrinogen. AB - After pronase digestion of bovine fibrinogen, the asparagine-linked glycans were released from the resulting glycopeptides by hydrazinolysis, and subsequently re N-acetylated. Two sialylated glycans were isolated by ion-exchange chromatography. Their primary structure has been determined by methylation analysis and 360-MHz 1H-NMR spectroscopy. The structures proposed to be present in the native glycoprotein are as follows: (formula: see text). PMID- 4029153 TI - Correlation of computed tomography and conventional hypopharyngography findings in hypopharyngeal tumours. AB - Accuracy and clinical application of computed tomography (CT) and conventional hypopharyngography have been evaluated in 32 patients with hypopharyngeal carcinoma. Radiologic results were compared with endoscopic findings. Equivalent CT and hypopharyngographic findings were found in 17 cases. In 13 cases, more data about the tumours were obtained by CT. Submucous infiltration of surrounding tissues, destruction of cartilaginous structures and enlarged lymph nodes were demonstrated only by CT. More information about functional changes were obtained by hypopharyngography. During hypopharyngography, a disorder in the act of swallowing was shown in 11 cases. Axial tumour diameter could be defined more exactly using hypopharyngography. PMID- 4029154 TI - Calcified subdural haematomas associated with arrested hydrocephalus--late sequelae of shunt operation in infancy. AB - Calcified chronic subdural haematomas (SDH) and features of arrested (compensated) hydrocephalus were demonstrated by skull radiography and cranial computed tomography (CT) in two children who had no neurological deficit. Ventricular surgical drainage had been performed 8 and 11 years prior to admission and the haematomas remained subsequently undetected. The following presentation will serve to illustrate the characteristic radiological features of this entity, the issue of management, and includes a review of the literature. PMID- 4029155 TI - Disk-space hypodensity in CT: the first radiological sign of postoperative diskitis. AB - Five patients with recent postoperative diskitis were examined with plain lumbar films and/or multidirectional tomography and CT. Three patients with normal recovery after lumbar disk herniation operation served as controls of the CT findings. Plain films and tomography showed intervertebral disk space narrowing and end plate erosions two and one-half to four weeks after the onset of symptoms. CT detected significant hypodensity of the affected disk spaces as compared to the controls. This was the first recognizable sign of diskitis in three patients and appeared as early as ten days after the onset of symptoms. PMID- 4029156 TI - Angio-CT techniques. AB - In over 1000 body CT studies different techniques of fast contrast medium injection were used: single bolus injection, continuous fast drip infusion and multiple sequential bolus injections. Advantages and indications of different techniques are evaluated. PMID- 4029157 TI - Percutaneous management of iatrogenic arterial venous fistulas by coil spring occlusion. AB - Six patients with iatrogenic arterial venous fistulas (AVFs) underwent successful transcatheter occlusion with coil springs. Three patients had AVFs as complications of surgery and in two other patients the AVFs were due to insertion of the central venous catheters. One iatrogenic AVF occurred following transhepatic obliteration of gastroesophageal varices. Management of iatrogenic AVFs by transcatheter occlusion avoids additional surgery and reduces morbidity and hospital costs. Coil springs are highly suitable for occluding iatrogenic arterial venous fistulas. They need no special preparation, are readily available, inexpensive, and easy to use. PMID- 4029158 TI - CT evaluation of chest wall recurrences of breast cancer. AB - CT findings regarding chest wall recurrences in 19 breast cancers previously treated with radical mastectomy are reported. CT provides detailed information on the endothoracic extension of the tumoral spread. PMID- 4029159 TI - Computed tomographic follow-up in a case of Addison's disease. AB - Addison's disease of the adrenal glands presents with different pathological findings depending on the stage. In the acute phase the adrenal glands are bilaterally enlarged while in the chronic phase the glands are small and calcified. A case of Addison's disease with follow-up over a period of a year by CT is reported. CT showed the evolution of the adrenal glands from bilateral masses to small calcified glands. The differential diagnostic problems in the acute phase are also discussed. PMID- 4029160 TI - Fibular lipoma with areas of bone infarct calcification. AB - An anatomico-radiological study of a painful intraosseous lipoma of the fibula is reported. A blown up cortex and a rearrangement of surrounding cancellous bone trabeculae were observed. The lipoma contained two small bone infarcts. A radiological differential diagnosis with calcified chondroma as well as the pathogenesis of the condition are discussed. PMID- 4029161 TI - Analysis of an image quality assurance program. AB - Reject film analysis before and after the introduction of a quality assurance program showed a 45% decrease in rejected films. The main changes in equipment and routines were: Increased control of film processors and X-ray generators. New film cassettes and screens. Decreased number of film sizes. Information to and supervision of radiographing personnel. Savings in costs and increased income from an increased amount of out-patients corresponded to about 4.5% of the total cost of operating and maintaining the department. PMID- 4029162 TI - The effects of fluid-mechanical factors on MR imaging in the arterial model. AB - Blood flow is a significant factor in MR imaging. The purpose of this investigation was to study fluid-mechanical effects on MR imaging. MR images generated by the pulsatile flow of bovine blood in an elastic model of the aorta with both renal arteries were studied. The high-frequency pulse sequence was synchronized to an ECG trigger signal. It was demonstrated that different flow velocities, laminar and turbulent flow, and backward flow can be visualized with MR imaging. PMID- 4029163 TI - Energy response of LiF (TLD-100) and CaSO4:Dy TL dosimeters to different diagnostic spectra. AB - Energy response of LiF (TLD-100) and CaSO4:Dy TL dosimeters to different diagnostic X-ray spectra has been studied. Through energy response the X-ray spectrum influences the dose to be measured with a thermoluminescence dosimeter. The energy responses of both dosimeters were calculated with typical diagnostic high voltages 60-140 kVp and with 1-50 mmAl total filtrations for 2-pulse and constant potential generators. Theoretical X-ray spectra were used. Pulse form and small differences in high voltage and in total filtration do not cause any significant error in measured dose due to energy response. The ratio of the energy responses of CaSO4: Dy and LiF does not produce a sufficiently strongly sloping curve as a function of high voltage for the determination of the half value layer with typical diagnostic exposure values. PMID- 4029164 TI - Kinetics of monensin-induced swelling of Golgi apparatus cisternae of H-2 hepatoma cells. AB - In H-2 hepatoma cells grown in culture, a pattern of response to the sodium selective ionophore, monensin, was observed in which cisternal swelling commenced at one pole of the Golgi apparatus and was accompanied by the accumulation of swollen vacuoles in the cytoplasm in the absence of a decrease in the number of cisternae per stack. The results suggest that the swollen vacuoles are formed from Golgi apparatus cisternae that are replaced by formation of new cisternae. Depending on monensin concentration, between 2 and 4 such vacuoles accumulated per Golgi apparatus stack within 12.5 min after monensin addition. The rate of vacuole formation was greatest at 10(-6) M monensin and least at 10(-8) M monensin over the range 10(-5) to 10(-8) M monensin. The general pattern of early response to the ionophore is that formation of normal secretory vesicles is blocked, after which the Golgi apparatus continues to function for a time to release membrane as swollen cisternal units that accumulate in the cytoplasm at or near the trans Golgi apparatus face. These phenomena all precede the general swelling response normally observed in glutaraldehyde-fixed animal material and illustrate that the early dynamic responses to monensin are not confined to plant cells. PMID- 4029165 TI - Isolation of mouse megakaryocytes. I. Separation of two fractions enriched in different maturational stages. AB - Megakaryocytes (MK) were isolated from mouse bone marrow by centrifugation on discontinuous gradients of isotonic albumin or Percoll and characterized by acetylcholinesterase (AChE) staining. The apparent density distributions of MK varied greatly depending upon the nature of the gradient medium and the composition of the cell suspension buffer while the density range of the other bone marrow cells remained largely unchanged. The present findings also indicate that the unusual morphological and functional characteristics of MK may underlie the observed shift in their density profile. Thrombocytopoietic stimulatory factor (TSF) was administered to mice 18 h before killing to elevate the normally low numbers of earlier MK in the bone marrow and to improve the yield of immature MK during the subsequent isolation procedure. Cells belonging to earlier stages in maturation were separated from the more mature ones on discontinuous Percoll density gradients, providing a basis for further investigation of MK development. PMID- 4029166 TI - Isolation of mouse megakaryocytes. II. Functional and metabolic aspects of two different maturational stages. AB - Functional and metabolic parameters were compared in immature and mature megakaryocytes (MK) isolated from bone marrow of the mouse by Percoll density gradient centrifugation. Comparison of metabolic parameters revealed that the ability to take up serotonin was equal in both megakaryocytic fractions. The uptake of radioactively labeled adenine was increased in immature MK as compared with mature MK. Total adenosine triphosphate (ATP) content was enhanced during the differentiation from MK to platelets: immature MK: 5, mature MK: 29, platelets: 63 nmol ATP/mg protein. Since MK, like platelets, released ATP upon stimulation, thrombin-induced release was used as functional parameter to differentiate between secretable and non-secretable ATP compartments. Upon thrombin stimulation both MK fractions released about 25% of their total ATP as compared with about 40% secreted by platelets. Although the actual size of the non-secretable ATP pool was different in mature MK and platelets, they demonstrated similar percentages of retained ATP (20-25%) in contrast to a much higher retention (62%) by immature MK. The present findings suggest that the bulk of ATP is acquired by immature MK as they gain maturity, although some ATP is still obtained during even later stages of differentiation. This growing ATP pool could be attributed mainly to the enlargement of the secretable compartment during the transition of immature MK to mature MK. PMID- 4029167 TI - Relation of retinomotor responses and contractile proteins in vertebrate retinas. AB - Photoreceptors of many nonmammalian vertebrate species display pronounced light dependent movements which are absent in mammalian species. In order to further analyze the molecular basis of receptor movements and of simultaneous migration of melanin granules in pigment epithelial processes, we investigated the distribution of actin, myosin and the actin-binding muscular proteins alpha actinin and vinculin in the retina of various vertebrate species. The species investigated can be divided in two groups (i) those possessing retinomotor capacity (fish, frog, turtle, chick) and (ii) those in which retinomotor activities are negligible or absent (gecko, mouse, rat). Prominent bundles of actin filaments extending throughout the long axis of photoreceptor inner segments were only found in species possessing retinomotor capacity, while comparable actin filament bundles were absent or poorly developed in photoreceptors of species lacking significant retinomotor capacity. In all species examined, a well developed circumferential band of actin filaments was associated with the zonula adhaerens-like junctions between photoreceptors and Muller (glial) cells forming the external limiting membrane. This area was also identified as the exclusive site of myosin, alpha-actinin and vinculin (only in the chick, alpha-actinin-like immunoreactivity was also found along the photoreceptor actin filament bundles). Thus, the external limiting membrane may be important for both structural support and for providing a possible site of filament sliding for photoreceptor movements. In pigment epithelium actin, myosin, alpha-actinin and vinculin were concentrated circumferentially in the area of the terminal bar which has been previously shown to be contractile. In all species apical pigment-epithelial processes displayed actin-like fluorescence of varying intensities. Another site of actin-like staining were photoreceptor synaptic complexes which represent a well known site for synaptic plasticity. Immunoblotting studies on the avascular chick retina revealed polypeptide bands at Mr approximately 130 000, approximately 100 000, and 42 000 which were specific for vinculin, alpha-actinin and actin, respectively. A faint polypeptide band comigrating with thymus myosin heavy chain indicates myosin to be only a minor component of the retina (chick and fish). PMID- 4029168 TI - Fibroblasts from patients with Fanconi's anemia are not deficient in excision of thymine dimer. AB - Fibroblasts from a patient with Fanconi's anemia were reported to show a defective excision of pyrimidine dimer [15]. We developed a sensitive radioimmuno assay which is specific for thymine dimer, the main ultraviolet photoproduct, and reinvestigated the thymine dimer excision in fibroblasts from patients with Fanconi's anemia. The analysis of 7 Fanconi's anemia cell lines did not agree with the claim mentioned above that was derived from only one Fanconi's anemia cell line. All cell lines we studied, including the cell line used previously [15], excised thymine dimer from their DNA with excision rates similar to those of normal fibroblasts. Additionally, in two Fanconi's anemia and in two normal fibroblast cell lines the repair capacity was examined. PMID- 4029169 TI - Modulation of the digestive lysosomal system in Paramecium caudatum. II. Physiological effects of cytochalasin B, colchicine and trifluoperazine. AB - The heterophagic pathway of the digestive lysosomal system in Paramecium caudatum includes at least four steps: digestive vacuole (DV) formation, acidification condensation, lysosomal fusion-digestion, and defecation. The second and the third require about 20 min, during which DVs are not egested. Because these steps occur at predictable intervals, the mechanism for each can be explored by exposing labeled DVs to different drugs prior to each step. In this study the effects of cytochalasin B (CB), colchicine and the calmodulin antagonist, trifluoperazine (TFP), were studied. All three drugs inhibited DV formation in a dose-dependent manner when cells were pulsed with latex beads and a drug simultaneously. TFP was cytotoxic above 5 microM. Vacuole formation was completely shut down when cells were pre-exposed to 5 microM TFP for 13 min. At this level, the duration of the acidification step was lengthened, and the rate of defecation decreased with increasing exposure. These results suggest that these inhibitory effects may be more related to TFP's cytotoxicity than to its action on calmodulin-mediated process. Colchicine at 1 mM had no effect on the third or fourth step, but inhibited the acidification step so that DVs were egested later and at a slower rate. Exerting a differential effect on all four steps, CB inhibited DV release from the cytopharynx, egestion of defecation competent DVs at the cytoproct and lengthened the duration but did not block the lysosomal fusion-digestion step of the acidic DVs; it was most potent in blocking acidification, which prevented both lysosomal fusion with the labeled DVs as well as DV egestion, the latter for more than 50 min.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4029170 TI - Modulation of the digestive lysosomal system in Paramecium caudatum. III. Morphological effects of cytochalasin B. AB - Morphological explanations for the effects of cytochalasin B (CB) on the digestive vacuole system of Paramecium caudatum were sought using electron microscopic studies. Cytochalasin B (0.3 mM) essentially stopped vacuole release without stopping vacuole growth. Acidosome fusion with the new vacuoles was inhibited and was accompanied by the formation of discoidal vesicle-lined clumps of microfilament-like material next to these vacuoles. Vacuole membrane retrieval at the open cytoproct was inhibited and was accompanied by the loss of the microfilament network typical of this region. At 0.15 mM CB vacuole release and fusion of the acidosomes and lysosomes with the vacuoles were not stopped, but membrane retrieval at the cytoproct was affected. Cytochalasin B at the higher concentration also affected the movement of the horseradish peroxidase (HRP) labeled vesicles away from the nascent vacuole. Membrane retrieval by the formation of tubules of 35 to 50 nm diameter from membrane of early and late vacuole stages was also affected by CB. It is conceivable that all of these effects were the result of the disruption of membrane associated actin networks. By contrast, several highly organized microfilamentous systems in the cortex and oral region of these cells appeared to be unaffected by CB or dimethyl sulfoxide (DMSO) at the concentrations used. These results show that CB-susceptible structures assume a key role in the normal functioning of the digestive vacuole system and in vacuole membrane retrieval and reutilization in Paramecium. PMID- 4029171 TI - Distribution of intramembranous particles and filipin-sterol complexes in the cell membranes of Toxoplasma gondii. AB - Toxoplasma gondii possesses a plasma membrane covering the whole cell and, below it, two closely apposed unit membranes interrupted at the anterior and posterior tips of the parasite and at the micropore. Density differences of intramembranous particles (IMP) were observed among the various membranes. The polyene antibiotic filipin was used for the detection of sterols in freeze-fractured membranes of the parasite. Protuberances with a mean diameter of 38 nm, indicative of the formation of filipin-sterol complexes, were seen in the P and E faces of the plasma membrane. The density of filipin-sterol complexes on the P and E faces of the plasma membrane was 130 +/- 45 and 101 +/- 50 protuberances/micron2, respectively. Few or no protuberances were seen on both fracture faces of the intermediate and inner membranes. The results obtained are discussed and compared with those obtained in other parasites enclosed with a complex membrane system. PMID- 4029172 TI - Species differences in the handling of lysosomotropic metals and Triton WR 1339 by rat and Chinese hamster liver. AB - The study was undertaken in order to understand the reasons for the distinct differences in the elimination rate of lanthanides and transuranium elements from the liver of different mammalian species. The binding of monomeric 239Pu in livers of rats and Chinese hamsters was analyzed by density gradient centrifugation and electrophoresis. It was concluded that this nuclide is initially bound to lysosomes in liver of rats and Chinese hamsters. The influence of Triton WR 1339 (TWR) on the density of lysosomal marker enzymes from rat and Chinese hamster liver at day 4 was very similar for both animal species but the TWR induced shift persisted in Chinese hamsters up to day 60 whereas in rat liver the lysosomal density increased again with time. Electron microscopic inspection confirmed the similarity of the initial reaction of hepatocyte lysosomes. However, after 60 to 70 days typical TWR induced "tritosomes" were absent from rat hepatocytes but could be found regularly in hepatocytes from Chinese hamsters. The elimination rate of 3H-activity from liver injection of 3H-TWR was lower in Chinese hamsters than in rats. It was concluded that the differences in elimination rate of lanthanides and transuranium elements from liver of various mammalian species and the differences observed after TWR injection might reflect differences in the composition or function of the lysosomal system in the livers of different mammalian species. With respect to the transport of certain heavy metals the rat liver is not a reliable model for human liver. PMID- 4029174 TI - Procedure for isolating micronuclei from rat kangaroo cultured cells containing individualized chromosomes. AB - Micronuclei are small interphase nuclei containing part of the genome; the DNA content of the smallest micronuclei is equivalent to one chromosome. For analysis by biochemical method and by cytofluorometry of interphase micronuclei containing a single chromosome, several isolation and purification procedures were tested and checked by fluorescent microscopy using the DNA dye Hoechst 33 342 and electron microscopy. Micronucleation of rat kangaroo epithelial cells was induced by colchicine treatment for three days. Micronuclei were isolated in a low ionic strength buffer containing collagenase, with concomitant mechanical shocks. Eighty % of the micronuclei were released after 3 to 7 min, with minimum nuclear breakage. Subsequent filtration through several polycarbonate filters 12, 8 and 5 micron in diameter enabled purification of the smallest micronuclei without aggregates or debris. Micronuclear morphology was well preserved, as shown by electron microscope observations. Therefore, we established the optimal conditions allowing gentle mass isolation of individual micronuclei of cultured PtK1 cells, compatible with flow cytometry analysis. PMID- 4029173 TI - The effect of dexamethasone on albumin production by fetal rat hepatocytes in culture. AB - Hepatocytes derived from 15 and 19-day gestation rats synthesize and secrete albumin during culture. Albumin secretion is maintained when the culture medium is supplemented with dexamethasone but declines in its absence. The fall in secretion rate correlates with the level of albumin messenger RNA in the respective cultures. Even when dexamethasone is present, the level of albumin production in 19-day gestation hepatocytes is 6 to 7 times greater than that observed in hepatocytes derived from 15-day gestation rats. Immunocytochemical studies were undertaken to establish whether the difference in secretion rate was due to a difference in the amount of albumin produced by all the hepatocytes of the respective cultures or whether there were fewer hepatocytes which were capable of synthesizing albumin in the less mature liver. The results indicate that albumin production is reduced in all hepatocytes when cultured in the absence of dexamethasone. PMID- 4029175 TI - Plasma membrane changes in hepatocytes from normal and regenerating rat liver. PMID- 4029176 TI - Visualization of the interaction of native and modified low density lipoproteins with isolated rat liver cells. AB - Morphological characteristics of the interaction of low density lipoproteins (LDL) and acetylated low density lipoproteins (AcLDL) with rat liver cells are described. These liver cell types are mainly responsible for the catabolism of these lipoproteins in vivo. Isolated rat liver Kupffer, endothelial, and parenchymal cells were incubated with LDL or AcLDL conjugated to 20 nm colloidal gold. LDL was mainly internalized by Kupffer cells, whereas AcLDL was predominantly found in endothelial cells. Kupffer and endothelial cells displayed different morphological characteristics in the processing of these lipoproteins. Kupffer cells bound LDL at uncoated regions of the plasma membrane often at the base of pseudopodia, and internalized the particles via small smooth vesicles. These uptake characteristics differ from the classical LDL uptake pathway, as described for other cell types, and may be related to the unique recognition properties of the receptor of Kupffer cells as observed in biochemical studies. Liver endothelial cells bound AcLDL in coated pits, followed by rapid uptake. Uptake proceeded through small coated vesicles, and after 5 min of incubation large (600-1200 nm) electron-lucent vacuoles (endosomes) with AcLDL-gold particles arranged along the membrane region were present. The endosomes were often associated closely with the cell membrane which might enable direct recycling of AcLDL receptors. These observations might explain the high efficiency of these cells in the processing of modified LDL in vivo. PMID- 4029177 TI - A new method of preparing gold probes for multiple-labeling cytochemistry. AB - A new method is described for preparing colloidal gold particles in any size between approximately 3 and 17 nm for electron microscopy. The gold particles are homogeneous in size (homodisperse). When bound to various proteins (e.g. IgG and protein A), the complexes were stable for long periods and suitable for affinity cytochemistry. We demonstrated the usefulness of the new gold probes bound to protein A for multiple labeling in a current immunocytochemical study on receptor mediated transport of IgA in human duodenal crypt cells. Other gold-protein complexes were useful for studying macromolecular arrangements at high resolution. PMID- 4029178 TI - Localization of the fibronexus at the surface of granulation tissue myofibroblasts using double-label immunogold electron microscopy on ultrathin frozen sections. AB - An intimate transmembrane complex of fibronectin-containing extracellular fibers and actin microfilaments termed the fibronexus has been observed at the adhesive surface of fibroblasts in vitro [19] and along the plasmalemma of myofibroblasts in vivo [22]. Although the observation of coincident actin and fibronectin immunofluorescence patterns in the latter work strongly suggested that the fibronexus is localized at the myofibroblast surface, we only obtained morphological evidence for its existence with electron microscopy. Therefore, in the present study, we have utilized a double-label immunoelectron microscopic technique to localize fibronectin and actin simultaneously in the putative fibronexuses of myofibroblasts within guinea pig granulation tissue, formed 7 to 9 days after skin wounding. This method employed rabbit antifibronectin and mouse anti-actin antibodies, followed by species-specific secondary antibodies conjugated to colloidal gold particles of different sizes. These probes were applied to the surfaces of ultrathin frozen sections mounted on grids. We found that fibronectin and actin were specifically localized on the respective external and internal components of myofibroblast fibronexuses. Our results suggest that specific transmembranous fibronectin-cytoskeletal complexes play an important role in the cohesion of granulation tissue. PMID- 4029179 TI - Diagnostic value of computerized exercise testing in men without previous myocardial infarction. A multivariate, compartmental and probabilistic approach. AB - The value of exercise testing for the diagnosis of coronary artery disease is disputed but very few studies have taken advantage of all recent improvements, namely computer averaging of the ECG signals, multivariate analysis of the data, a compartmental diagnostic approach and probabilistic interpretation of the results. These methods were tested in a group of 387 men who had a computer assisted multistage maximal exercise test; none had a history of myocardial infarction. In 284 symptomatic patients, the diagnosis was made by arteriography; 103 ostensibly healthy men were also included. The computer-averaged ECG signals (X, Y, Z) recorded at maximal exercise, maximal heart rate, blood pressure and workload, and the onset of angina pectoris during exercise were submitted to a multivariate stepwise discriminant analysis. The pretest likelihood for CAD was calculated from age and history; the post-test likelihood was calculated from Bayes' theorem and the average information content of several diagnostic methods was assessed in categorical and compartmental models. By multivariate analysis, 5 variables collected at maximal exercise were selected, namely the heart-rate, the ST60 segment level, the onset of angina during the test, the workload and the slope of the ST segment in lead X. The average information content of the analysis using 5 variables was 44% in a categorical model versus 55% in a compartmental model (P less than 0.001). For comparison, the information content of the analysis using the ST60 segment level alone was only 16% in the categorical model and 27% in the compartmental model. The clinical value of these diagnostic methods (categorical versus compartmental, univariate versus multivariate) was assessed by a probabilistic classification of the patients. The classification provided by the analysis of the ST60 segment changes was barely better than that one provided by the simple history. The probabilistic use of a multivariate and compartmental analysis of the data led to a significantly better and more accurate classification of the patients (83% of correct classification). PMID- 4029180 TI - Effects of cold stimulation on coronary haemodynamics during exercise in patients with coronary artery disease. AB - To assess if cold-induced vasoconstriction may persist during exercise and contribute to the development of myocardial ischaemia, we studied 11 patients with exertional angina and angiographically proven coronary artery disease, in all cases involving the proximal portion of the left anterior descending artery. Great cardiac vein flow (GCVF) was measured by the thermodilution technique and the coronary resistance of the abnormally perfused anterior region (ARCR) was calculated as the quotient of mean arterial pressure and GCVF. All patients performed a supine bicycle exercise test (ET1) until angina occurred. After recovery, they underwent a cold pressor test (CPT) and then performed a second exercise test (ET2) while cold stimulation was continued. During ET1, ARCR decreased (from 1.53 +/- 0.43 to 1.04 +/- 0.35 mmHg ml-1 min-1, P less than 0.001) as a result of the metabolic vasodilation, while it rose, although non significantly, during CPT despite the increase in double product (P less than 0.001), reflecting the augmented myocardial oxygen consumption. However, such abnormal response to CPT did not persist during ET2, because ARCR decreased to a value non significantly different from that achieved at peak ET1. In five patients, who showed a reduced exercise tolerance during ET2, ARCR dropped by 22% during ET2 compared with 34% decrease during ET1. However, such a difference was unlikely to account for the reduction in exercise tolerance, because the double product at peak ET2 was never lower than the corresponding value at peak ET1. Our data show that the inappropriate vasoconstriction induced by CPT in an abnormally perfused myocardial region does not persist during exercise, when metabolic vasodilation occurs.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4029181 TI - ECG findings and survival in very old people. AB - The electrocardiograms of 559 persons, 82% of the total population 85 years of age or over in the city of Tampere in 1977-1978, were evaluated according to the classification of the modified Minnesota code. The relative five-year survival rates matched by sex and age were calculated for subjects with various ECG findings. Of the series, 391 persons (70%) died during the five-year follow-up period. The lowest mortality rate was observed in those with no codable change or with minor abnormality in the ECG. Electrocardiographic abnormalities suggestive of ischaemic heart disease were associated with significantly increased mortality. In respect of single ECG changes the greatest mortality rate was found in subjects with atrial fibrillation or first-degree atrioventricular block revealed in the ECG. No increased risk of death was associated with left and right bundle branch block, supraventricular premature beats and ventricular premature beats. PMID- 4029182 TI - Electrophysiologic effects, antiarrhythmic activity and pharmacokinetics of cibenzoline studied with programmed stimulation of the heart in patients with supraventricular reentrant tachycardias. AB - Cibenzoline, an imidazoline derivative is a new antiarrhythmic agent. Its electrophysiological effects and antiarrhythmic properties were studied with programmed electrical stimulation of the heart in 12 patients with recurrent episodes of reentrant supraventricular tachycardia; atrionodal (5 cases), circus movement tachycardia involving an accessory pathway (6 cases), intraatrial reentry (one case). Cibenzoline was infused intravenously at a dose of 1 mg kg-1 to 1.75 mg kg-1 during sustained episodes of tachycardia and over 9 to 15 min. Cibenzoline shortened the sinus cycle length, moderately increased the transnodal conduction time and markedly lengthened the HV interval. The refractory periods of the atrioventricular (A-V) node, the atrium and the ventricle did not change. The effects of cibenzoline on accessory pathways used in the anterograde direction were measurable in 4 cases. Complete blockade of the bypass was seen in every case. In the retrograde direction the refractory period of the bypass could be evaluated; in 5 patients it lengthened systematically. Infused intravenously during epidoses of tachycardia, the drug terminated the rhythm disorder in 9 out of 12 cases. Tachycardia could still be initiated in 8 patients after i.v. cibenzoline (2 out of 5 A-V nodal tachycardias, 6 out of 6 circus movement tachycardias). The distribution of the drug followed a bicompartment pharmacokinetic model. The plasma levels at the end of infusion ranged from 1.34 to 3.19 microgram ml-1. Cibenzoline, primarily has class I antiarrhythmic properties and its well-understood pharmacokinetics should be of help in tailoring the treatment to the individual needs of the patient. PMID- 4029183 TI - Pre-operative sinus node function in adult patients with atrial septal defect (ostium secundum type). AB - The authors studied, pre-operatively, the sinus node function in adult patients with secundum atrial septal defect and large left-right shunts, using Holter ECG and electrophysiological tests. Sinus node electrophysiological tests were found abnormal in 17 out of 26 patients; on the contrary, Holter monitoring was always within normal limits. The authors believe that concealed sinus node dysfunction existing before surgical correction may be a cause of early, acute, and reversible, post-operative sick sinus syndrome. PMID- 4029184 TI - Clinical significance of nonclinical ventricular tachycardia induced in amiodarone-treated patients. AB - The clinical significance of sustained nonclinical ventricular tachycardia (VT) induced during electrophysiologic studies was studied in 10 amiodarone-treated patients. Nine patients had previous myocardial infarction while 1 patient had right ventricular dysplasia. All patients had only a single morphologic type of VT recorded during the multiple spontaneous episodes of tachycardia. After serial pharmacological electrophysiologic testing, the patients were placed on antiarrhythmic regimens which included amiodarone in all cases. These drugs did not prevent the induction of nonclinical VT in any of the 10 patients and of sustained clinical VT in 7 patients. Nonclinical VT was sustained, requiring cardioversion (7 patients) or rapid ventricular pacing (3 patients) for termination. After a mean follow-up period of 27 +/- 10 months (range 12 to 36 months), 4 patients did not exhibit recurrent VT, 3 patients with inducible clinical VT experienced a recurrent episode of clinical VT after 16, 27 and 49 months, respectively, 2 patients had nonarrhythmia related deaths after 11 and 12 months, and 1 patient died suddenly after 17 months. These results suggest that laboratory induction of sustained nonclinical VT in amiodarone-treated patients does not imply the likelihood of their future spontaneous occurrence and, therefore, their prevention may not be required. PMID- 4029185 TI - Recurrent myocardial infarction. 1. Natural history of fatal and non-fatal events. AB - 1306 men below 68 years of age who survived a first myocardial infarction (MI) during 1968-1977 were followed up between 2 and 12 years after discharge from hospital. The mean follow-up time was 6.5 years. The patients were unselected and paid regular visits to a Post-MI Clinic where treatment was standardized. The diagnosis of a non-fatal reinfarction was based on conventional clinical criteria, and the diagnosis of a fatal reinfarction on autopsy findings of a recent myocardial injury and/or a fresh coronary thrombus. The autopsy rate was high and the follow-up of endpoints was complete. The total cumulative rate of endpoint free patients was 64% at 5 years and 50% at 10 years follow-up. The total mortality rate was 19% at 5 years and 33% at 10 years follow-up. The total cumulative rate of a first reinfarction was 28% at 5 years and 37% at 10 years follow-up (80% non-fatal and 20% fatal). 63 patients suffered more than one reinfarction. The mortality rate was strongly associated with age. In contrast the rate of non-fatal reinfarctions was independent of age. PMID- 4029186 TI - Recurrent myocardial infarction. 2. Possibilities of prediction. AB - 1306 men less than 68 years of age who survived a first myocardial infarction (MI) during 1968-1977 were followed up between 2 and 12 years. The mean follow-up time was 6.5 years. The patients were unselected and paid regular visits to a Post-MI Clinic where treatment was standardized. The autopsy rate was high and the follow-up of endpoints was complete. The diagnosis of a non-fatal reinfarction was based on conventional clinical criteria, and the diagnosis of a fatal reinfarction on autopsy findings of a recent myocardial injury and/or a fresh coronary thrombus. The patients were randomly assigned to two halves. One was used only for derivation of the predictive models, and the other only for validation. Common clinical variables judged to be prognostically important were selected. Among variables available at discharge from hospital a history of hypertension, angina pectoris or diabetes before the MI and the maximal serum ASAT during the MI were independently related to reinfarctions during the follow up. A predictive index was formed and validated. The rate of reinfarction among risk quartiles in the validation sample increased from 24 to 38% (P = 0.003). The aetiologic fraction (the percent of reinfarctions predicted by the index) was 24%. Among variables from the follow-up only cessation of smoking after the MI had independent predictive power. A new predictive index including this variable was formed and validated. The reinfarction rate in the risk quartiles increased from 15 to 39% (P less than 0.001). The aetiologic fraction was 44%. When only reinfarctions occurring before the median follow-up time of 21 months were considered, the aetiologic fraction was 62%. PMID- 4029187 TI - Intraindividual comparison of intravenous ajmaline and quinidine in patients with sustained ventricular tachycardia: effects on normal myocardium and on arrhythmia characteristics. AB - Intraindividual comparison of the acute response to intravenous quinidine and to intravenous ajmaline was performed in 23 patients with sustained ventricular tachycardia (VT) who underwent serial electrophysiological studies. In each patient, sustained VT could be reproducibly initiated by programmed ventricular stimulation during control studies. Inducibility of sustained VT was prevented after quinidine in 6 of the 23 patients (26%) and after ajmaline in 8 of the same 23 cases (35%). Agreement between the effects of both drugs was not significant: 2 patients had a similar response to both quinidine and ajmaline and 11 patients did not have a response to either of the two drugs, resulting in a total of only 13 patients (57%) who had a similar response to both drugs. In the 11 non responders with inducible sustained VT before and after both drugs, quinidine and ajmaline caused qualitatively and quantitatively similar alterations of VT characteristics including a significant prolongation of the interval between the initiation extrastimulus and the first beat of VT by 38 and 42% (P less than 0.01), an increase in VT cycle length by 15 and 22% (P less than 0.01) and a prolongation of the QRS duration during VT by 15 and 18% (P less than 0.01), respectively. In all 23 patients, quinidine and ajmaline caused a quantitatively similar prolongation of ventricular refractoriness by 11 and 9% (P less than 0.05), of the QRS duration at sinus rhythm by 10 and 15% (P less than 0.01) and of the QTc interval by 13 and 10% (P less than 0.05), respectively. Thus, ajmaline and quinidine appear to have similar electrophysiological effects on both normal myocardium and on indirect parameters of reentry; in individual patients with sustained VT, however, such electrophysiological similarities do not result in significant agreement of preventive responses. PMID- 4029189 TI - Esophageal ECG recording--a valuable diagnostic tool in dual chamber pacing. AB - The interpretation of the ECG of a dual chamber pacemaker necessitates the identification of atrial activity. This is a prerequisite for the evaluation of pacemaker function and for the correct adjustment of programmable pulse generators. The assessment of atrial capture in standard 12-lead ECGs is, however, sometimes rather difficult. Esophageal ECG recording by means of a reusable unipolar electrode, inserted transnasally, and connected to a standard ECG recorder, is a simple, rapid and inexpensive method for the reliable identification of P-waves. Clinical examples are presented to illustrate the value of this technique in determining atrial capture and as a tool for the differential diagnosis of pacemaker-involved tachycardias. The use of esophageal ECG recording in the clinical follow-up of patients with dual chamber pacemakers is recommended. PMID- 4029188 TI - Morphological findings in apparently idiopathic ventricular tachycardia. An echocardiographic haemodynamic and histologic study. AB - In order to investigate the anatomic substrate of 'idiopathic' ventricular tachycardia (VT) 10 patients with chronic recurrent VT and no apparent sign of heart disease underwent an echocardiographic, haemodynamic and histologic study (5 males, 5 females: mean age = 40 +/- 11 years). In the patients with a left bundle branch block morphology of VT (7 cases), four showed findings compatible with an arrhythmogenic right ventricular dysplasia or a right ventricular cardiomyopathy. In the other three all examinations were normal with the exception of endomyocardial biopsy, which showed slight non specific changes in two. Of the remaining 3 cases (characterized by a right bundle branch block morphology of VT or by the presence of polymorphic VT) one had histologic evidence of myocarditis while another developed dilated cardiomyopathy. Macroscopic and/or microscopic ventricular abnormalities are frequently found in patients with VT which appears idiopathic. In these cases myocardial disease is frequently progressive, despite optimal control of VT. PMID- 4029190 TI - Afterload reduction by nifedipine--the acute haemodynamic response to exercise in hypertensive subjects. AB - In 16 people with essential hypertension, heart rate (HR), blood pressure (BP) and relative cardiac volumes were measured at rest and during submaximal upright exercise before and after 10 mg of sublingual nifedipine using radionuclide ventriculography. In 10 patients who had had no previous therapy (BP 152/103 +/- 5/3 mmHg) nifedipine produced a fall in BP of 6/12 +/- 3/3 mmHg (SEM) and a rise in HR of 15 +/- 5 bpm (P less than 0.001). This was associated with a rise in LVEF of 0.07 +/- 0.02 (P less than 0.005) and in cardiac output of 44 +/- 9%, presumably as a result of ventricular offloading. The cardiac response to exercise given the different starting values, was unchanged by nifedipine. Thus the HR was 101 +/- 6 bpm at rest after nifedipine and on exercise rose to 124 +/- 6 bpm (P less than 0.001): stroke volume was +22 +/- 8% at rest after nifedipine and rose to +43 +/- 12% on exercise. Thus cardiac output which had increased by 44 +/- 9% after nifedipine increased by 100 +/- 10% from the initial value. In 6 patients pre-treated with atenolol (100 mg) and with similar resting BP (158/101 +/- 5/4 mmHg) there was a fall in BP of 32/15 +/- 3/2 mmHg after nifedipine which was greater than in the previously untreated group (P less than 0.01). In this group HR increased by 8 +/- 3 bpm (P less than 0.05). Following nifedipine the exercise response was similar given the different starting values.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4029191 TI - Cross-sectional echocardiographic findings in a patient with pyogenic pericardial effusion and cardiac tamponade. PMID- 4029192 TI - Role of verapamil in junctional rhythm. PMID- 4029193 TI - Fourth joint meeting of the working groups of the European Society of Cardiology. 19-21 September, 1985, Brighton, U.K. Abstracts. PMID- 4029194 TI - Placental hormones as possible markers in gynaecological cancer. AB - Two placental hormones (human chorionic gonadotropin and human chorionic somatotropin) were assayed in serum of patients bearing a wide variety of malignant tumours. The incidences of these hormones were found to be higher among female patients. Further studies revealed that the incidence was high in patients with malignant tumours of the gonads, breast, uterus and cervix. It was shown that these hormones are the products of tumour cells and that they are released in circulation. Studies on cervix cancer suggest that they may be useful aids in following the course of therapy. PMID- 4029195 TI - Undenuded invasive cervical carcinomas erroneously treated by cauterization. AB - Two cases of occult invasive carcinoma of the cervix have been reported with emphasis on diagnostic failure and subsequent inappropriate treatments. A prompt replacement with malignant cells simulating dysplasia or carcinoma in situ was observed at the sites of cauterization preoperatively. However, histology of postoperative specimen showed apparent invasiveness in both cases and lymphatic metastases in one of them. These findings have led us to a concept that the present cases may represent a variety of occult carcinomas, which is in between the common and verrucous types of squamous cell carcinomas. PMID- 4029196 TI - Hormonal receptors in vulvar tissues. AB - Since 1982 we have been associating the study of hormonal receptors with the histological examination of the vulvar lesions in an attempt to interpret the action mechanism of steroids on the vulva, to find possible correlations between histological pictures and receptorial order and to find a possible predictive "marker" toward therapeutic and prognostic ends. In our Laboratory assays for androgen, estrogen and progesterone receptors were performed with the Dextran Charcoal technique in 41 patients with vulvar dystrophy; 20 of whom had atrophic dystrophy and 21 with hypertrophic dystrophy. Another 24 patients with vulvar carcinoma were studied; 23 with epidermoid carcinoma of various differentiation grades and only one case of Paget's Disease. None of the three receptors assayed could be considered a predictive or prognostic marker in the approach to neoplastic forms. The levels of the progesterone receptor appears increased in the case of dystrophies. This justifies the hypothesis of a hormonal involvement in the pathogenesis of the lesion, as has already been documented by the beneficial effects of therapy with topical steroids. PMID- 4029197 TI - Diagnostic value of the different methods for evaluation of bone metastasis in breast carcinoma. AB - A group of 263 patients portraying breast Ca staged through the clinic, is studied and evaluated by different methods of diagnosis as regards bone metastasis. A clinical investigation of bone pain, specific laboratory determinations for Ca-P-alkaline phosphatase; bone X ray, bone scintigraphy with gamma camera are carried on. In some pre-selected cases bone biopsy performed. A 15.9% of the patients with breast Ca showed bone metastasis. Scintigraphy was positive in a 100% of these cases, pain in 62%, X ray in 41%. The final results of laboratory were discarded since they were not considered reliable. Highly specific positive zones for bone metastasis and benign bone pathology were detected when sectioning the spine in the classical zones. A methodological sequence is proposed. PMID- 4029198 TI - Clinical significance of plasma lipid-bound sialic acid (LBSA) and carcinoembryonic antigen (CEA) in gynaecologic cancer patients. AB - A comparison between plasma lipid-bound sialic acid (LBSA) and carcinoembryonic antigen (CEA) in gynaecologic cancer patients has been performed. The LBSA level appears more specific then the CEA, especially for ovarian cancer. This finding has promoted a longitudinal study to show if LBSA test may prove a reliable marker of disease in ovarian cancer patients. PMID- 4029199 TI - Our experience in the second look laparotomy for ovarian cancer. AB - Our experience in second-look laparotomy for ovarian carcinoma is reported: in seven patients the second-look was negative; in two patients a neoplastic dissemination was found; in three patients we performed a debulking surgery. PMID- 4029200 TI - Radio-chemotherapeutic management of bone diffusion from breast carcinoma. AB - A combined modality therapy (irradiation plus low-dose Adriamycin and Cyclophosphamide) was delivered to 41 patient affected by extensive bone diffusion from breast carcinoma. A 36% (15/41) objective response rate was obtained, no change was also detectable in 36%, while progressive disease in 28% (11/41). A subjective response was achieved in 37/41 patients, i.e. 90%. The Authors remark the difficulties in evaluating the objective response of metastatic bone to therapy and confirm the keystone role of radiation therapy in the palliative treatment of breast cancer skeletal diffusion. PMID- 4029202 TI - Colpocytology in children: 3 cases of botryoid sarcoma. AB - We have examined some aspects of the colpocytological preparations of 3 children affected by leucorrhea accompanied by bleed up, from which was diagnosed botryoid sarcoma. The characteristic element met in the preparations was the altered epithelial maturation in prepuberal children; the presence of groups of intermediate and superficial cells, with nuclei sometimes diskaryotic, of anucleate scales and of discharging phenomena. In one case it was possible to observe even neoplastic and slightly differentiated cells. The Authors underline the usefulness of carrying out a colpocytological examination in the initial diagnostic stage with children affected by leucorrhea, above all if this is accompanied by bleeding. PMID- 4029201 TI - "In vitro" effect of progesterone on alpha-L-fucosidase activity of human endometrium. AB - Alpha-L-fucosidase activity was found to be increased in organ cultured normal endometrium and in endometrial adenocarcinoma compared with non cultured tissue. The enzyme activity was lowered with addition of progesterone to the medium. Non cultured adenocarcinoma showed a higher activity compared with non cultured normal endometrium. PMID- 4029203 TI - Struma ovarii presenting with ascites: a difficult diagnostic problem. PMID- 4029204 TI - Residual cervical stump cancer (true cancer) and residual cancer of the cervical stump (coincident cancer). Casuistics and therapeutic results in the period 1955 1979. AB - 176 cases of cervical stump cancer have been reviewed. "Coincident cancer" and "True cancer" distinction has been made. Histological features, therapeutic plane and survival have been reported. PMID- 4029205 TI - Stromal and peripheral eosinophilia in cervical carcinoma. AB - One hundred cases of Stage IB cervical carcinoma treated with radical hysterectomy and pelvic lymphadenectomy at University Hospital of Jacksonville, Florida between 1973 and 1982. Eight patients were found to have tumor stromal eosinophilia on pathology review. Thirteen patients showed eosinophilia in their peripheral smears. Statistical analysis did not reveal a significant recurrence rate in patients with either peripheral or stromal eosinophilia. PMID- 4029206 TI - Steroids receptors in physiological and pathological features of the cervix. AB - The presence of ER and PgR in human cervical tissues was investigated. The material consisted of receptor measurements in tissue sample obtained from normal and abnormal colposcopical pictures (leukoplakia, mosaic, punctation, atypical transformation), in 38 outpatients. The receptor assays were performed by a dextran-coated-charcoal (DCC) technique. PMID- 4029207 TI - Fourier analysis on ungated time-activity curves. AB - The frequency content of the ungated radionuclide time-activity curves for left and right ventricles was analyzed using a power spectrum estimation technique. This technique was applied to ten patients. It was observed that 75% of the contraction power of any ventricle was contained in the fundamental and at least 98% contained in the fundamental plus the first harmonic. Patients presenting bigeminy and trigeminy had a completely different spectrum distribution which calls for a different interpretation. Low frequency spectrum lines have been observed at breathing frequency. Up to 62% of the total power may be contained in those spectrum lines. PMID- 4029208 TI - Do iodinated fatty acids undergo a nonspecific deiodination in the myocardium? AB - The intracellular and subcellular distribution of 16-(123I)-iodo-9-hexadecenoic acid were studied in isolated rat hearts, perfused with or without glucose. At various time intervals after injection, cardiac lipids were extracted and the activity was determined for all fractions and all lipid classes. The total cardiac activity was maximal within 1 min postinjection and most of the activity was in the aqueous phase. The presence of glucose in the perfusion medium induced an increase of total cardiac and organic fraction activities. In the latter fraction, activity was very low for FFA, but high for triglycerides (TG), and especially polar lipids. The presence of an exogenous substrate, led to a more active esterification of fatty acids. Coronary effluent analysis showed, in the hydrophilic phase, a lower activity spike in the presence than in the absence of glucose. In the mitochondrial fraction most activity occurred in the organic phase, especially as polar lipids. In the nonmitochondrial fraction, activity was much higher in the aqueous phase. At 90 s postinjection of 1-14C-palmitic acid, over 80% of the myocardial activity was found in the hydrophilic fraction, which indicates, as for the iodo-fatty acid (IFA), an immediate and important oxidation, especially without glucose. These data seem to prove that IFA is taken up by the myocardial cell, subsequently enters the mitochondria and, without an early deiodination, is oxidized with iodide release. Changes in IFA metabolism, consecutive to modifications of glucose concentration in the perfusion medium can be observed by external detection of the myocardial activity curve. Omega Iodinated fatty acids do not undergo a nonspecific deiodination and are therefore well suited for an external study of myocardial metabolism. PMID- 4029209 TI - Factor analysis of 81mKr lung ventilation studies. AB - Factor analysis of dynamic structures (FADS) summarizes data depending on time and space in a few elementary components. Each of them associates a time-activity curve (factor) and the spatial distribution of the corresponding events. The aim was to evaluate the patterns, the number of components, and their possible link to physiology when FADS was applied to scintigraphic images representing a composite of a 81mKr ventilation cycle. In a study of 26 patients (10 normal, 16 pathologic), components were found that represent: (1) a rapid and steeply changing ventilation factor, corresponding mainly to bases in normal subjects and whole lung fields in patients, (2) a slower expiration and shorter inspiration ventilation factor distributed throughout both lung fields in all patients, (3) a constant activity curve, with an inspiratory activity peak distributed over both lung fields and the large airways, and (4) a factor including a phase shift with respect to the first; this was found significantly more often in patients with pathology. PMID- 4029210 TI - Potential of SeHCAT retention as an indicator of terminal ileal involvement in inflammatory bowel disease. AB - The absorption of 75Se-23-selena-25-homotaurocholate (SeHCAT) was compared with vitamin-B12 absorption and conventional radiography in 44 patients with inflammatory bowel disease. The retention of SeHCAT was normal in 11 patients with ulcerative colitis but was abnormally low in 9 patients with terminal-ileal resection, 9 out of 14 patients with small-bowel Crohn's disease and in 2 out of 10 patients with Crohn's colitis. The 5 patients with small-bowel Crohn's disease and normal retention had either inactive disease or no radiological evidence of terminal ileal involvement. Measurements of the absorption of vitamin B12 did not discriminate between these groups, and there was very poor correlation between B12 and SeHCAT absorption (r = 0.506, P less than 0.05). There was extremely good correlation of SeHCAT retention measured using a wholebody counter with that measured using an uncollimated gamma camera (r = 0.96, P less than 0.001). The results suggest that SeHCAT retention may prove complementary to conventional methods of assessing small-bowel disease in patients with inflammatory bowel disease. As measurement by gamma camera is feasible, this test can be used in most departments of nuclear medicine. PMID- 4029211 TI - Combined radionuclide and radiocontrast arthrography for evaluating hip arthroplasty. AB - Twenty-two patients had combined radiographic and radiocolloid arthrography. The two procedures were in agreement in 86% of the patients as to whether the femoral component was loose or not. Fourteen patients has surgical revision of the prosthesis and in 3 (23%) radiographic arthrography was falsely negative. No false negative results were obtained with radiocolloid arthrography thus far. The radionuclide method cannot be used to assess the acetabular component. PMID- 4029212 TI - 99mTc-HIDA dynamic scintigraphy for the diagnosis of gastroesophageal reflux of bile. AB - In 5 patients with partial gastric resection and esophagitis, in whom esophageal pH metry was unable to demonstrate significant gastroesophageal reflux (GER), we administered i.v. 5 mCi (185 MBq) of 99mTc-HIDA, the patient lying under a computer-assisted LFOV gamma camera. When gallbladder image was evident, caerulein was administered i.v. at a physiologic dose in order to induce gallbladder contraction, and in the subsequent 45 min the patient was asked to perform a standard series of manoeuvres that increase the intraabdominal pressure (Valsalva, etc.) and favour GER. Scintigraphic images and time/activity curves obtained from areas of interest corresponding to gastric remnant and distal esophagus showed that at least one of these manoeuvres in each case was followed by the appearance of the radiocompound in the distal esophagus, indicating a 99mTc-HIDA-tagged bile GER. Consequently, we believe that HIDA-GER dynamic scintigraphy may be more useful than esophageal pH metry in demonstrating the biliary origin of an esophagitis. PMID- 4029213 TI - Quality control of commercial 99mTc-human albumin kits. AB - The quality of a number of commercial human albumin kits used at Danish hospitals for preparation of 99mTc-labelled human serum albumin has been investigated by column chromatography and HPLC. In general, the radiochemical purity was found to be low (75% or less). In some cases with a poor radiochemical purity, the main radiochemical impurity, 99mTc-labelled tin colloid, amounted to 29% or more. A large molar tin to albumin ratio seems to lead to a low radiochemical purity and it is suggested that products with a high content of stannous chloride may be more correctly termed 99mTc-albumin/tin-colloid kits. PMID- 4029214 TI - Splenic defect on 99mTc-sulfur colloid scintigraphy but not on CT in a patient with pancreatic carcinoma. AB - A 99mTc-sulfur colloid (99mTc-SC) scintigraphic study of a patient with pancreatic carcinoma invading the splenic hilum demonstrated a discrete focal defect of the spleen, while computed tomography (CT) showed a normal spleen. The patient underwent splenectomy and no pathology was found in the spleen. The tumor invasion into the splenic hilum may have caused the defect shown in the 99mTC-SC study, reflecting splenic reticuloendothelial (RE) cell dysfunction, while CT might well represent anatomic structures only. This discrepant finding between functional (99mTc-SC) and anatomic (CT) imaging modalities may be explained by the fact that the impairment of the phagocytic function of the spleen apparently was not severe enough to cause structural changes detected by CT or gross and microscope examination. PMID- 4029215 TI - Lung scintigraphy. PMID- 4029216 TI - First-pass metabolism of nomifensine in dogs. AB - Nomifensine (1 and 5 mg/kg) was administered to dogs orally and intravenously. The pharmacokinetics of the drug was evaluated. Nomifensine was rapidly absorbed from the gastro-intestinal tract reaching maximum concentration at 0.5-1 h. The peak levels were directly proportional to the doses administered. The elimination half-life was 6 h and only very small amounts were found in blood at 24 h after administration. The apparent volume of distribution (Vd) was 120-149 1, suggesting an extensive distribution of the drug throughout body fluids and tissues. The area under the serum concentration-time curve (AUC) obtained after oral administration was significantly smaller than that after intravenous administration indicating incomplete bioavailability of the drug in oral form. The conjugation of nomifensine after the two different administration routes was also studied: the conjugation reaction was in equilibrium at 15 min after oral administration, while after intravenous administration, equilibrium was not reached until 1-1.5 h. The metabolism of nomifensine occurred in the gastrointestinal membranes and or in the liver during the absorption process; the first-pass effect was marked. PMID- 4029217 TI - Bioavailability of hetacillin in rats after liver enzyme induction by various inducers with or without protein binding properties. AB - The serum levels and the half life of ampicillin derived from Hetacillin after administration of the latter to a total of 61 rats classified in 7 groups were determined. Each of these groups was pre-treated for 15 days with the following inducers; phenobarbital, diphenylhydantoin, diazepam, chlorpromazine and phenylbutazone. The control group received saline. The d-glucaric acid concentration in the urine prior to and after the administration of inducers and the liver weight were taken as enzyme induction indices. Results showed a positive correlation between the indices of induction and the levels of ampicillin originating from hetacillin with a significant correlation coefficient between the serum levels of ampicillin and urine d-glucaric acid for all drugs studied. The different effect of the various drugs indicated that they could be classified into the following two groups: a) those that induced a significant increase of the levels and half life (t1/2) of ampicillin. The effect was significant in decreasing order for phenylbutazone (r = 0,990), diazepam (r = 0,990) and diphenylhydantoin (r = 0,753). b) those which initially resulted in a significant increase of the levels of ampicillin and thereafter in a decrease with a significant shortening of its t1/2 too. The effect was most significant for phenobarbital (r = 0,887) and less so for chlorpromazine (r = 0,800). Only for these two drugs was a significant and actually negative correlation observed between d-glucaric acid and t1/2 that is: phenobarbital (r = -0,967) chlorpromazine (r = -0,752). Results suggest an interaction of Hetacillin and the above inducers. PMID- 4029218 TI - Pharmacokinetics and bioavailability of viqualine, a new antidepressant. AB - A high performance liquid chromatographic assay was developed for plasma and urine levels measurement of viqualine. The assay was used to study the disposition of 25 mg intravenous and oral single doses in five healthy subjects. Two exponential terms were required to describe the disposition of the drug after intravenous and oral administration. The bioavailability of oral viqualine averaged 80%. The mean apparent half-life was 12.1 +/- 1.9 and 11.9 +/- 1.4 h (mean +/- s.e.m., n = 5) after 25 mg I.V. and oral dose respectively. The apparent volume of distribution (Vdss) were 1578 +/- 132 1 (after I.V. administration) and 1572 +/- 201 1 (after oral administration). The body and renal clearances were respectively 1.56 +/- 0.31 1.h-1. kg-1 and 1.57 +/- 0.31 1.h-1. kg-1, after 25 mg bolus I.V. PMID- 4029219 TI - Kinetics of ketamine and its metabolites in rabbits with normal and impaired renal function. AB - The plasma levels of ketamine, an anaesthetic, and its metabolites were studied in 10 rabbits with normal renal function and in 9 rabbits with varying degrees of experimentally induced renal impairment. All the animals received a single bolus type i.v. dose of 10 mg/kg of the drug. The results obtained reveal an apparent inhibition of the biotransformation of ketamine in rabbits with renal impairment in which the drug is accumulated. The plasma half-life of ketamine ranged from 0.74 h in rabbits with normal renal function to 2.6 h in the animals with severe renal impairment. The plasma levels of norketamine (metabolite I) did not alter significantly in states of renal impairment. However, the kinetics of the other metabolite (II), dehydronorketamine, did change significantly in renal impairment, due to its high renal excretion capacity. PMID- 4029220 TI - Pharmacokinetics of pirazolac--a new anti-inflammatory drug--in human volunteers. I. Absorption, disposition, biotransformation and excretion. AB - The absorption, disposition, biotransformation and excretion of the nonsteroidal anti-inflammatory drug pirazolac were investigated in 6 volunteers (3 males, 3 females, age 50 greater than years) after intravenous and oral administration of 50 mg 14C-pirazolac as an aqueous solution of the sodium salt. Pirazolac was very rapidly and completely absorbed and bioavailable when orally administered in a dose of 50 mg in solution. Maximum pirazolac levels in plasma of 6 micrograms/ml (30% of dose in total plasma volume) were already reached after approx. 20 minutes. No metabolites were detectable in the plasma. Pirazolac was eliminated from the plasma in two phases with half-lives of 3 hours and 16 hours, respectively, regardless of administration route. After intravenous and oral administration approximately 80% of the dose was excreted with the urine and approximately 15% with the feces within 7 days, indicating a complete excretion of 14C-radioactivity. In urine, approximately 10% of the dose was identified as unchanged pirazolac and 70% as pirazolac ester glucuronide. PMID- 4029221 TI - Metabolic fate of Qinghaosu in rats; a new TLC densitometric method for its determination in biological material. AB - Since the sixties, the emergence of malarial parasites resistant to the most potent anti-malarials has posed a serious problem to the therapy of malaria. Qinghaosu, a new sesquiterpene isolated from a Chinese medicinal herb Qing-hao (Artemisia annua Linn) is being used for the treatment of malaria in China with good results even in cases resistant to common anti-malarial agents. In this paper, a sensitive method of high specificity using TLC for the determination of Qinghaosu in biological specimens and in the study of the metabolism of the drug in rats is described. Qinghaosu was shown to be completely and rapidly absorbed after oral administration. However, a very low plasma level was obtained even after a dose of 300 mg/kg. Liver was found to be the chief site of its inactivation. When Qinghaisu was given intramuscularly, significant and more persistent plasma levels were detected. Qinghaosu was shown to pass the blood brain and blood-placenta barriers after i.v. injection. Very little unchanged Qinghaosu was found in the urine and feces in 48 hours regardless of administration route (i.v., i.m. or p.o.). PMID- 4029222 TI - [Validity of the Eppendorf Mood-Drive Scale]. AB - The paper examines the validity of the Eppendorfer Mood and Drive Scale (ESTA III). ESTA III is a self-rating instrument for evaluating the effect of therapy and for studying the course of affective psychoses. Empirical research on the validity of the scale has been carried out solely by the author of the test. Subsequent to a critical review of hitherto existing research on the validity of the instrument, our own validity studies are discussed. Our studies cast doubt on the concurrent validity of the instrument (comparison with the adjective check list/EWL-K). Analysis of our own data and Reanalysis of the data published by the author of ESTA III do not support the construct validity of the instrument. PMID- 4029223 TI - The influence of age on optokinetic nystagmus. AB - The influence of age on optokinetic nystagmus (OKN) was studied in 63 healthy subjects, who were divided into three groups according to their age, group I (20 39 years), II (40-59 years) and III (60-82 years). It was found that on average maximal OKN velocity decreases considerably with age, from 114 degrees/s in group I to 93 degrees/s in group II and 73 degrees/s in group III. Two mechanisms participate in the generation of OKN, the so-called 'fast' component and 'velocity storage' component. The 'fast' component leads to immediate changes in slow phase nystagmus velocity and is related to smooth pursuit eye movements. The 'velocity storage' component causes more gradual velocity changes and expresses itself during optokinetic afternystagmus (OKAN). To study the relative contribution of these two components, maximal smooth pursuit and OKAN velocity were determined in addition to the maximal OKN velocity for the same individuals. It was found that both smooth pursuit and OKAN performance decrease with age. Consequently the maximal OKN velocity, which depends on both factors, is even more affected than smooth pursuit eye movements. PMID- 4029224 TI - Thiamine deficiency and nervous system function disturbances. AB - Thiamine is important for oxidative metabolism, and B1 deficiency is thought to give rise to polyneuropathies. A group of male Wistar rats (n = 15) received a vitamin B1 deficient diet (group-a), and the pair fed control group (n = 20, group-b) received a normal diet with no vitamin deficiency. A second control group (group-c) was fed unrestrictedly with a standard diet (n = 19). All animals were examined for 25 weeks. The sensory nerve conduction velocity, the compound radicular, spinal and brain stem responses and the SEP were derived for tail and hind paw stimulation. The examination was repeated at 6-week intervals. There was no difference in nerve conduction between group-a and -b, but for both groups the conduction velocity was significantly slower than in group-c. The SEP latencies were significantly increased in group-a compared with group-b and also with group c. The spinal and cerebral latencies were delayed in group-a. The diameters of myelinated nerve fibres were decreased in group-a compared with group-b, and in group-b compared with group-c. The results indicate that a specific polyneuropathy exists as a result of B1 deficiency, and that the sequelae of the lack of thiamine are pronounced in the CNS. PMID- 4029225 TI - Hypoplasia of the basilar artery. Three case reports. AB - Three patients, aged 65, 70, and 80 years, respectively, with hypoplastic basilar artery are presented. To our knowledge no similar case has been reported in the literature till now. In one of the cases, the hypoplasia of the basilar artery was an incidental finding. The other two patients had transient neurological symptoms considered characteristic of circulatory insufficiency in the vertebrobasilar system. One of the latter two patients died of acute myocardial infarction and the other patient died after developing occlusion in the cervical part of the right internal carotid artery. The exact nature of hypoplastic basilar artery is uncertain. The possible mechanisms of its occurrence are discussed. PMID- 4029227 TI - European Society for Surgical Research. Abstracts. 20th congress, Rotterdam, May 6-8, 1985. PMID- 4029226 TI - [Dimensions of the Hamilton Depression Scale. Factor analysis studies]. AB - The results of factor analysis of HAMD are not unitary. Studying the stability in course and the independence of selection criteria for the population we rated two groups (n = 107, n = 98) of inpatients with HAMD; these groups differ in nosological selection criteria. We furthermore rated one group at different timepoints (before treatment and 3 weeks after). The one-factor-solution is the only stable one and the only one which is independent from selection criteria. In all groups the one-factor-solutions show a high similarity with other published solutions of the German version of HAMD. But there is no way to extract a general factor. Thus the ability of HAMD in judging the severity of depression is doubtful. Ways are discussed to circumvent this problem. PMID- 4029228 TI - Extracorporeal shock-wave lithotripsy: one-year experience with the Dornier lithotripter. AB - Extracorporeal shock-wave lithotripsy (ESWL) has now been in clinical use for more than 4 years. In October 1983, the second kidney lithotripter in the world was installed in our department and, from then until October 1984, 800 treatments were performed on 733 patients. Our results confirm the promising reports published by the Munich group. Furthermore, it was possible to extend the range of indications by combining ESWL with percutaneous procedures, such as percutaneous nephrolithotomy and ureteroscopy. As a result only 7% of all patients who were referred to our hospital with urinary stones (4% of renal stone patients and 15% of those with ureteral stones) had to undergo open surgery. PMID- 4029229 TI - Bladder neck reconstruction using an anterior bladder flap in post-prostatectomy incontinence. AB - Bladder neck reconstruction using an anterior bladder flap was used in 10 patients with total diurnal urinary incontinence, persistent 1 year after suprapubic (n = 6) or transurethral (n = 4) prostatectomy. 8 patients achieved symptomatic improvement, 6 of them with excellent or good results. Bladder neck reconstruction is undoubtedly able to correct post-prostatectomy incontinence, provided there is no residual bladder neck obstruction or alteration of the bladder musculature due to previous surgery. These cases should be considered for artificial sphincter implantation. PMID- 4029230 TI - The Mainz pouch (mixed augmentation ileum 'n zecum) for bladder augmentation and continent urinary diversion. AB - A new technique for fashioning an ileocecal pouch, applicable for both bladder augmentation and continent urinary diversion, is described. A low pressure reservoir is achieved by antimesenteric longitudinal transsection of ileum and cecum and formation of a pouch from the cecum and two ileal loops. The antireflux procedure consists of submucosal tunnel implantation of the ureters into the cecum. Clinical application of the operative technique in 4 cases for bladder augmentation and in another 6 cases for urinary diversion has proven the validity of our functional concept: all patients with Mainz pouch bladder augmentation are completely dry day and night with normal intervals of bladder evacuation. Of the 6 patients with Mainz pouch urinary diversion, 2 rely on a an all alloplastic stomal prosthesis for continence, another 2 have achieved continence with isoperistaltic ileo-ileal invagination, and the remainder are awaiting implantation of a sphincteric device. PMID- 4029231 TI - Nonrefluxing colon conduits with a modified ureterocolonic anastomosis. AB - Urinary diversion by means of a colon conduit is particularly advantageous. In comparison with the ileal conduit an antireflux ureterocolonic anastomosis can be created, thus preventing renal damage in patients with a long life expectancy. Herein the authors present the results of 5 years experience with colon conduits and Pagano's ureterocolonic anastomosis. PMID- 4029232 TI - Factors influencing the time long-term indwelling Foley catheters can be kept in situ. AB - To study the factors that influence the frequency of unscheduled catheter changes, patients with long-term indwelling Foley catheters were followed up for 48 weeks. A marked interindividual difference in the need for unscheduled changes was noted. The amount and composition of the encrustations precipitated on the catheters and urine osmolality influenced the frequency of unscheduled catheter changes. There was no correlation between the time a catheter had been in situ and the amount of encrustations on catheters changed on schedule after various times in situ. This indicates that time does not govern the amount of encrustations accumulated. PMID- 4029233 TI - Surgical treatment of vesicoureteral reflux with bilateral medialization of the ureteral orifices. AB - The technique of bilateral medialization of the ureteral orifices, as proposed by Gil-Vernet, has been used with minor modifications in a series of 14 patients for the surgical treatment of vesicoureteral reflux. Its major advantages are its technical simplicity and bilateral treatment in all cases. PMID- 4029234 TI - A prospective survey of the indications and morbidity of circumcision in children. AB - Both the British Medical Association and the American Academy of Pediatrics recommend that circumcision should only be performed for medical reasons. No one has ever described which reasons are actually used, nor measured the morbidity of the procedure. Of 140 boys coming to day-case elective circumcision between the ages of 3 months and 14 years (mean 4.3 years), the commonest cause was a congenital phimosis (42.8%). Four (2.8%) patients required acute readmission postoperatively, and a further 4 developed meatal stenosis, requiring a formal meatotomy. Of 99 patients followed up in detail, 46% vomited, 36% oozed, 19% did not pass urine for more than 12 h and 26% could not wear pants for more than 7 days. Childhood circumcision has an appreciable morbidity, and should not be recommended without a medical reason. PMID- 4029235 TI - Upper urinary tract obstruction in children caused by Candida fungus balls. AB - 2 children with upper urinary tract obstruction from Candida fungus balls are reported. A presumptive diagnosis, made on the basis of clinical and radiological findings, was confirmed by microscopic examination of urinary sediment. Medical treatment was successful in both patients. Since Candida infections can occur in patients with altered host resistance, this should alert clinicians to the possibility of fungal involvement when radiolucent filling defects are found in the renal pelvis. Such a presumptive diagnosis can then lead to a correct approach with conservation of renal function. PMID- 4029236 TI - Open instillation of formalin for cyclophosphamide-induced hemorrhagic cystitis in a child. AB - A child with massive hematuria, produced by cyclophosphamide-induced cystitis, was treated with open bladder instillation of formalin. To prevent vesicoureteral reflux, we inserted two Fogarty catheters. Intraoperative retrograde cystography was made to confirm that there was no reflux, extravasation or passage of contrast per urethra. The postoperative result was good with cessation of hematuria. PMID- 4029237 TI - Endocrine-paracrine cells in prostatic carcinoma and clinical course of the disease. AB - The occurrence of endocrine-paracrine (argyrophil and argentaffin) cells in normal and hyperplastic human epithelia has long been recognized. 40 consecutive prostatic carcinomas were studied histochemically and ultrastructurally. The authors consider only clinically evaluable cases and discuss the clinical significance of the presence of endocrine-paracrine cells on the basis of their personal experience. PMID- 4029238 TI - Antegrade ureteroscopy for stone removal. AB - Antegrade ureteroscopy, using the 11-French ureteroscope via a percutaneous transrenal access, provides safe and easy endoscopic exploration of the ureter above the level of the iliac vessels. The technique has proven to be reliable and effective for the removal of obstructing proximal ureteral calculi: all of the 22 patients who underwent antegrade ureteroscopy were stone-free after treatment. Since the introduction of this new technique in our department, no more open surgery has been required to manage ureteral calculi. PMID- 4029239 TI - Primary localised amyloidosis of the urethra. AB - Primary localised amyloidosis of the urethra is a rare disease. Successful treatment of the few reported cases has been achieved by per urethral resection, open excision and internal urethrotomy. PMID- 4029240 TI - Nephrosis with varicocele: probable renal vein thrombosis. AB - A 3-year-old boy with relapsing nephrosis presented with a left sided varicocele. Echographic studies demonstrated enlargement of the left kidney, and there was delayed excretion on renal scintigraphy suggesting the presence of renal vein thrombosis. The varicocele resolved with remission of his nephrosis. PMID- 4029241 TI - Physicians as employees of the pharmaceutical industry. AB - It is evident that a knowledge of medicine is indispensable for the discovery, development and, indeed, for the marketing of medicines. That is why the pharmaceutical industry has to employ physicians in research and marketing. However, this group of employees has always presented special problems. What I have to say relates to physicians, i.e. doctors who have trained as clinicians and who, initially at least, were drawn to clinical medicine. My remarks do not apply to pharmacologists, toxicologists and biochemists, i.e. natural scientists, who may have pursued their basic studies in a medical faculty and obtained a degree in medicine. PMID- 4029242 TI - Effects of oral prajmaline bitartrate on exercise test responses in patients with coronary artery disease. AB - The safety, tolerability and haemodynamic effects of oral prajmaline bitartrate were assessed in a double-blind, randomized, placebo-controlled, crossover trial in 21 patients with stable angina pectoris and coronary artery disease. No serious side-effects occurred. Prajmaline bitartrate produced no statistically significant changes in resting heart rate or systolic blood pressure or in work capacity on the treadmill, or in heart rate or systolic blood pressure at maximum exercise compared to placebo values. No new arrhythmias or conduction abnormalities were produced in any patient. We conclude that oral prajmaline bitartrate is well tolerated and can be given safely to patients with coronary artery disease without producing deleterious haemodynamic effects or changes in exercise capacity. PMID- 4029243 TI - Long-term effects of pinacidil in hypertensive dialysis patients. AB - In an open study, thirteen chronic dialysis patients with nonvolume dependent uncontrolled hypertension were treated with pinacidil for a mean period of 43 weeks. Seven patients were taking concomitant antihypertensive therapy. Twelve patients achieved long-term blood pressure control on a mean dose of 33 mg/day. The baseline supine blood pressure was 184/116 mmHg. After 1 week it had fallen to 161/95 mmHg and blood pressure control was maintained over the study period. Patient weight remained stable. The baseline reading was 61.6 kg and at the end of the study it was 59.7 kg. Pulse rate did not change significantly. For the eight patients not taking beta-blockers the mean change in pulse rate was 7.6 beats/min supine and 6.3 beats/min erect (NS). Pretrial urea and creatinine were 27.6 mmol/l and 1027 mumol/l and after 25 weeks they were 29.6 mmol/l and 1087 mumol/l, respectively (NS). Four patients had ECG evidence of left ventricular hypertrophy before the study and one on completion of the trial. Five patients showed correction of T-waves on their ECG's. Six patients experienced side effects, none of which warranted withdrawal of treatment. These findings suggest that pinacidil is a valuable alternative treatment for hypertensive dialysis patients. PMID- 4029244 TI - Treatment of essential hypertension and hypertension associated with renal impairment with pinacidil: a new vasodilator. AB - Twenty patients with uncontrolled hypertension were treated with pinacidil for a mean period of 43 weeks (range 10-63 weeks). All patients achieved and maintained significant reductions in blood pressure. The supine blood pressure at baseline was 184/116 mmHg; after one week it was 161/95 mmHg and at 43 weeks it was 138/79 mmHg. The mean dose of pinacidil was 30 mg/day. There was no significant difference between the two groups with respect to the dose of pinacidil or the blood pressure response. Pulse rate and weight remained stable for the group as a whole. Five patients were not taking beta-blockers. The mean baseline pulse rate for this group was 78 beats/min and when maintained on pinacidil it was 82 beat/min (NS). Six patients were not taking diuretics. The mean baseline weight for this group was 78.5 kg and while maintained on pinacidil it was 79.2 kg (NS). There was no occurrence of oedema, hirsutism or first dose phenomenon. The mean glomerular filtration rate and renal plasma flow for the renal plasma flow for the renal group was 35.4 ml/min and 192.3 ml/min before pinacidil and after six months they were 32.7 ml/min and 183.2 ml/min (NS) respectively. Six patients experienced minor side-effects. We conclude that pinacidil is a potent, well tolerated antihypertensive agent which merits further study. PMID- 4029245 TI - Drug acetylation and expression of lupus erythematosus. AB - Acetylator phenotype was measure in 58 patients presenting to a skin clinic with discoid lupus erythematosus (DLE) and in 51 normal healthy subjects. Twenty seven of the patients with DLE were found to have evidence of systemic lupus erythematosus (D+SLE). Frequency of slow acetylator phenotype was 58% in all DLE patients, 52% in those with D+SLE and was no different from the 57% in controls. The distribution of acetylator phenotypes within the groups with DLE and those with D+SLE was similar to controls. Severity of DLE was assessed as number of skin lesions and median lesion count was 11.5 in slow acetylators and 10 in fast acetylators but in D+SLE median lesion count was 22 in slow acetylators and 12 in fast acetylators, and there was a significant inverse relationship between lesion count and rate of acetylation; scores for systemic involvement showed no relationship. We conclude that there is no difference in the frequency or distribution of slow acetylator phenotype between normal subjects and patients with DLE with or without SLE but that actual rate of acetylation may determine severity of expression of the disease in slow acetylators. PMID- 4029246 TI - Pharmacokinetics of verapamil in patients with renal failure. AB - The pharmacokinetics of verapamil was studied in patients with end-stage chronic renal failure and in normal subjects after i.v. injection of 3 mg and a single oral dose of 80 mg. Plasma levels of verapamil and its active metabolite norverapamil were measured by HPLC. After i.v. injection, the terminal phase half life and total plasma clearance of verapamil in both groups were similar. Haemodialysis did not change the time course of plasma verapamil levels after i.v. administration. After a single oral dose, the plasma levels of verapamil and norverapamil in both groups of subjects were similar. Subsequently, normal volunteers and patients with renal failure were treated for 5 days with oral verapamil 80 mg t.d.s. There was no difference between the 2 groups of subjects in the trough and peak levels of verapamil or of norverapamil. Intravenous and oral administration of the calcium channel blocking agent had similar effects on blood pressure, heart rate and the PR-interval in the electrocardiogram in both groups. The study demonstrated that the disposition of verapamil was similar in normal subjects and in patients with renal failure. PMID- 4029247 TI - Effects of transdermal scopolamine upon psychological test performance at sea. AB - The effects of transdermal scopolamine upon objective psychological performance assessments and self reports of feeling states, were investigated with volunteer subjects at sea. Scopolamine and placebo patches were administered on consecutive days in a counterbalanced order. Psychological performance was assessed 24 h following each transdermal patch. Choice reaction time and code substitution performance levels were not significantly changed, but letter cancellation errors were significantly more frequent following transdermal scopolamine. Transdermal scopolamine caused significantly more reports of dry mouth. More subjects were also unable to undertake the performance tests following scopolamine than placebo, due to difficulties in focusing on the test materials. However despite deleterious side effects with some personnel, others responded positively to the scopolamine patch. As noted by other workers, responses to the transdermal scopolamine patch seem to be quite variable. PMID- 4029248 TI - Impairment of caffeine clearance by chronic use of low-dose oestrogen-containing oral contraceptives. AB - The effect of chronic (greater than 3 months) administration of low-dose oestrogen-containing (less than 50 micrograms oestrogen) oral contraceptives (OCS) on the pharmacokinetics of caffeine has been examined in a treated females matched with 9 non-smoking, drug-free, healthy control females of similar age, weight and ethnic origin. Each subject received 162 mg caffeine base orally after an overnight fast. OCS subjects had a prolonged elimination half-life of caffeine, (mean 7.88 h vs 5.37 h in the controls). This was the result of marked impairment of the plasma clearance of caffeine (1.05 vs 1.75 ml/min/kg, respectively) with no change in apparent volume of distribution (0.685 in OCS vs 0.7501/kg in the control group). The absorption parameters determined were peak plasma caffeine concentration (3.99 vs 4.09 micrograms/ml) and time to peak concentration after drug administration (1.52 vs 0.79), which was moderately prolonged in OCS users. Thus, caffeine clearance, previously reported to be a specific marker of cytochrome P-448 activity in man, is decreased by chronic OCS use. This suggests that OCS may cause significant impairment of this enzyme activity as assessed in vivo. With chronic caffeine consumption, OCS users are predicted to have an increased steady-state plasma caffeine concentration as compared to non-OCS users. PMID- 4029249 TI - Personality and theophylline pharmacokinetics. AB - Thirteen volunteers received an iv dose of theophylline followed by blood sampling for 8 h to calculate pharmacokinetic parameters. Ten patients with asthma undergoing chronic dosing with slow release aminophylline underwent 12 h of blood sampling to calculate theophylline clearance. Both groups completed an Eysenck Personality Inventory (EPI) from which was derived scores for neuroticism (N) and extroversion (E). Using multiple regression analysis no independent effect of either N or E score on theophylline clearance or half-life could be demonstrated. PMID- 4029250 TI - Effect of probenecid on isofezolac kinetics. AB - The interaction between isofezolac and probenecid has been studied with the aid of a specific HPLC assay for isofezolac in plasma and urine. 8 healthy adult volunteers received a single 40 mg oral dose of isofezolac before and after 3 days of loading with 0.5 probenecid t.i.d. There was an increase in the maximum plasma isofezolac concentration from 2.44 to 3.38 micrograms X ml-1 when probenecid was given. The AUC of isofezolac in plasma increased from 6.73 to 11.28 micrograms X h X ml-1. After the last dose in a 7 day treatment with 40 mg isofezolac t.i.d., there was an increase in the maximum plasma isofezolac level from 2.84 to 4.96 micrograms X ml-1 when probenecid was given. The rate of absorption of isofezolac was not affected. An increase in the AUC of isofezolac in plasma was observed from 11.74 to 26.34 micrograms X h X ml-1. The major effect of probenecid on isofezolac metabolism was a 50% reduction in total isofezolac (free + conjugates) excreted inurine. Because of this interaction, patients given isofezolac combined with probenecid will have a higher steady state plasma level of isofezolac than when probenecid is not administered. PMID- 4029251 TI - Intravenous and intramuscular pharmacokinetics of recombinant leukocyte A interferon. AB - Interferon is currently being evaluated for the treatment of disseminated cancer and viral diseases. Alpha interferons have shown to be effective in the treatment of a number of malignancies. Recombinant leukocyte A interferon (rIFN-alpha A) is an alpha interferon produced by recombinant DNA techniques. A kinetic evaluation of rIFN-alpha A following intravenous and intramuscular administration has not been adequately defined. The present study was designed to evaluate the kinetics of rIFN-alpha A following intravenous and intramuscular administration of 3, 9 or 18 X 10(6) units to patients with disseminated cancer. A preliminary report of this study was presented at the meeting of the American Society for Clinical Pharmacology and Therapeutics in San Diego, March 1983 (1). PMID- 4029252 TI - Effect of rifampicin treatment on hepatic drug metabolism and serum bile acids in patients with primary biliary cirrhosis. AB - Six patients with primary biliary cirrhosis (PBC) were treated with a daily oral dose of 600 mg rifampicin for 2 weeks to induce the hepatic metabolism of drugs and bile acids. On rifampicin 5 of 6 patients experienced a pronounced decrease of their pruritus. In all patients the oxidative cytochrome P-450 dependent drug metabolism was induced as shown by an increase of antipyrine-clearance from 36.3 +/- 8.8 to 80.6 +/- 20.1 ml/min and an enhanced urinary excretion of 6-beta hydroxycortisol from 454 +/- 1.99 to 1607 +/- 362 micrograms/24 h. Furthermore, in all 6 patients the serum alkaline phosphatase declined. In the 3 cholestatic patients (bilirubin greater than 1.0 mg/dl) the serum concentration of total and conjugated bile acids was strikingly reduced. Thus, rifampicin is an inducer of hepatic metabolism in PBC-patients, ameliorates the pruritus and can lower serum concentrations of alkaline phosphatase and bile acids. PMID- 4029253 TI - Plasma protein binding of ritodrine at parturition and in nonpregnant women. AB - The binding of ritodrine HCl in whole plasma from healthy nonpregnant women, parturients and matched umbilical venous plasma and in solutions of HSA and alpha 1-AGP has been studied by equilibrium dialysis. Binding to plasma from nonpregnant subjects and HSA was independent of ritodrine concentration over a wide range. The free fraction in plasma was high and significantly different between groups of nonpregnant (alpha = 0.64), parturient (alpha = 0.68) and matched umbilical venous plasma (alpha = 0.75). It would seem that variability in transplacental transfer of ritodrine, as a result of plasma binding fluctuations, will be minor. PMID- 4029254 TI - Effect of atenolol on red blood cell deformability. PMID- 4029255 TI - Ageing and acetylator phenotype as determined by administration of sulphadimidine. PMID- 4029256 TI - The lymphoproliferating cells of MRL-lpr/lpr mice are a polyclonal population that bear the T lymphocyte receptor for antigen. AB - Mice bearing the recessive gene lpr develop an age-dependent, massive lymphoproliferation, primarily in the lymph nodes (LN), with associated autoimmunity. LN cells from these mice express T cell receptor protein on the cell surface at 50-70% of normal levels. Normal levels of T cell receptor alpha, beta and gamma mRNA were found in these cells as compared to normal LN cells. Southern blot analysis of MRL-lpr/lpr LN DNA showed rearrangements in 80-90% of the chromosomes at the beta gene loci. The pattern of rearrangement indicated that a polyclonal rather than monoclonal expansion of T cells occurred. These data support a lymphokine-induction model of lymphoproliferation in MRL-lpr mice. PMID- 4029257 TI - Enhancement of IgG anti-carrier responses by IgG2 anti-hapten antibodies in mice. AB - Isologous IgG2a and IgG2b anti-hapten antibodies injected along with trinitrophenylated or fluoresceinated keyhole limpet hemocyanin (KLH) were found to considerably stimulate primary IgG responses to the carrier protein in mice. No such stimulation was observed with IgG1, IgM and IgA anti-hapten antibodies. Depending on the antigen antibody combination, the amplification obtained after a single injection of IgG2-complexed haptenated KLH ranged from 20- to 1000-fold. By comparison, secondary responses were only marginally enhanced (approximately 3 fold) when IgG2-complexed rather than free antigen was used to boost irradiated recipients previously reconstituted with primed spleen cells. The IgG2-mediated enhancement was effective over a wide range of antigen/antibody ratios, did not require the use of high affinity antibodies and occurred whatever the route of injection. The stimulation was specific for the complexed antigen and developed to the same extent whether complexes were formed in vitro or in vivo. A comparable stimulation of the anti-carrier response was obtained with several other haptenated proteins but with formaldehyde-treated diphtheria and tetanus toxoids inhibition rather than stimulation was observed. PMID- 4029258 TI - Characterization of [3H]5-hydroxytryptamine uptake within rat cerebrovascular tree. AB - The in vitro uptake of tritiated serotonin ([3H]5HT) was studied in a preparation of rat extracerebral arteries. The uptake of [3H]5HT was time- and temperature dependent and of high affinity; linear regression analysis gave a Km value of 6.48 X 10(-7) M for the specific uptake. Bilateral superior cervical ganglionectomy was without effect on [3H]5HT uptake while it significantly reduced the uptake of tritiated norepinephrine by the preparation of rat extracerebral arteries. The serotonergic neurotoxin 5,7-dihydroxytryptamine and lesions to both the medial and the dorsal raphe nuclei caused a marked loss of [3H]5HT uptake but did not change the uptake of tritiated norepinephrine. Competition studies with norepinephrine, desimipramine (a noradrenergic uptake blocker), nomifensine (a dopaminergic uptake blocker) and fluoxetine (a 5HT uptake blocker) confirmed the specificity of the [3H]5HT uptake mechanism. Histoautoradiographic studies showed the highest density of silver grains at the level of the adventitial-medial border of the basilar artery. Fluoxetine inhibited the accumulation of silver grains within the adventitial-medial border in the blood vessel studied. The present data further support the view that a neuronal serotonergic system may play a role in the control of blood flow in the cerebrovascular tree. PMID- 4029259 TI - The cardiovascular effects of oxytocin in conscious male rats. AB - In conscious, chronically instrumented normotensive male Wistar rats intravenous (i.v.) administration of oxytocin (OXT) (greater than or equal to 100 ng) induced a dose-related biphasic change in mean arterial pressure (MAP). This consisted of an initial pressor effect accompanied by bradycardia and a decrease in cardiac output (CO), followed by a more prolonged fall in MAP which reached a maximum 30 min after injection and was accompanied by an increase in CO. The more specific (Thr4,Gly7]OXT analogue (0.01-10 micrograms i.v.) caused a dose-related fall in MAP and a rise in CO which reached a maximum after 15-30 min. Similarly in spontaneously hypertensive rats of the stroke prone strain (SHRSP) an initial pressor effect and delayed fall in MAP were apparent after OXT (0.1 and 10 micrograms i.v.) only the decrease in MAP being evident with the [Thr4,Gly7]OXT analogue. These responses were significantly larger than those observed in Wistar Kyoto controls. The pressor effects are therefore interpreted to be due to vasopressin receptor activation while the depressor effects appear to be oxytocin specific. In sinoaortic denervated rats, OXT (0.1 and 10 micrograms i.v.) induced an enhanced initial pressor effect with a much reduced reflex bradycardia and fall in CO. A larger and more prolonged delayed fall in MAP was apparent with both OXT and [Thr4,Gly7]OXT accompanied by a decrease in CO when compared to sham operated controls. Intracisternally (i.c.) administered OXT (0.05-10 ng) had no effect on MAP or heart rate.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4029260 TI - Pharmacological evidence for selective inhibition of gastric acid secretion by telenzepine, a new antimuscarinic drug. AB - The new antisecretory drug, telenzepine (4,9-dihydro-3-methyl-4-[(4-methyl-1 piperazinyl)acetyl]-10H-thieno-[3,4 - b][1,5]benzodiazepin-10-one), was investigated for its inhibition of functionally intact muscarinic receptors involved in gastric acid secretion in rabbit fundic glands, perfused mouse stomach in vitro, perfused rat stomach in situ, gastric fistula in rats and dogs with a Heidenhain pouch. The effects on these receptors were contrasted with effects on receptors located on smooth muscle and heart, i.e. isolated rat urinary bladder, stomach and atrium. The results were compared to those values obtained with nonselective antimuscarinic drugs (N-methylscopolamine, atropine) and the selective M-1 antagonist pirenzepine. Telenzepine was found to be 4-10 times more potent than pirenzepine with respect to depressing both gastric acid secretion and smooth muscle or myocardial responses. Based on -log EC50 and pA2 values, both drugs exhibited a similar selectivity profile differing from the pattern of effects observed with atropine or a second reference compound, zolenzepine. As compared with atropine, telenzepine exhibited a 5 fold higher relative affinity to muscarinic receptors involved in gastric acid secretion. It was concluded that telenzepine is selective to discriminate between muscarinic receptors mediating gastric acid secretion and affecting muscle contractility and that this finding supports the concept of muscarinic receptor heterogeneity. PMID- 4029261 TI - Interaction of amoxapine with muscarinic cholinergic receptors: an in vitro assessment. AB - Amoxapine, an antidepressant with a rapid onset of therapeutic efficacy and great utility in psychotic depression, has been reported to produce anticholinergic side effects in man similar to those observed with imipramine and amitriptyline. To establish its cholinergic disposition, amoxapine and its metabolites 7 hydroxyamoxapine and 8-hydroxyamoxapine, have been evaluated by determining their effects on quinuclidinyl benzilate (QNB) binding to membrane fractions of rat and human brain, on the carbamoylcholine-stimulated accumulation of inositol phosphates in rat cerebral cortex and on the acetylcholine-induced contraction of the guinea pig ileum. In all three preparations, amoxapine was found to be a considerably weaker antagonist of muscarinic cholinergic receptors than either imipramine (4-27 fold) or amitriptyline (51-300 fold). These results indicate that for amoxapine, no correlation exists between the magnitude of muscarinic receptor inhibition and the extent of 'anticholinergic' side effects found in the clinic. Neither the metabolites of amoxapine nor species differences could account for this discrepancy. PMID- 4029262 TI - Bradykinin antagonizes morphine-induced analgesia in rats. AB - The intraventricular injection of 5 micrograms of bradykinin or Met-Lys bradykinin in rats antagonized the increase in nociception threshold induced by morphine (5 micrograms i.c.v. or 10 mg/kg i.p.) in the tail flick test. The effect of the two kinins was prevented by atropine (30 mg/kg i.p.). The results suggest that bradykinin counteracts opiate activity in the central nervous system by enhancing acetylcholine release. PMID- 4029263 TI - The release of lyso-PAF from guinea-pig lungs. AB - Lyso-PAF was detected after ionophore challenge in the effluent of lungs of guinea-pigs exposed to oxygen and perfused through the pulmonary circulation as well as of control lungs perfused through the airways. Lyso-PAF is probably the inactive metabolite of PAF-acether which could not, itself, be detected in the lung effluents. PMID- 4029264 TI - Organ specificity of epithelial cells grown in tissue culture from explants obtained from various levels of the rat gut. AB - Monolayer cultures of epithelial cells grown from explants of fetal rat small intestine can differentiate into columnar as well as goblet cells in tissue culture (Kondo et al., Exp cell res 153 (1984) 12) [9]. In this study we have cultured tissue from various levels of the fetal rat gastrointestinal tract in order to characterize those cell types that can be cultured from these tissues and to determine the growth potential of these cells using this culture system. Explants of esophagus and forestomach tissue yielded monolayer outgrowths of squamous epithelial cells which grew as closely apposed polygonal cells capable of developing cornified envelopes. Explants of the glandular portion of the stomach yielded outgrowths of densely packed cells which were more pleiomorphic and which did not desquamate or form cornified envelopes. Explants of small intestine and colon yielded outgrowths of epithelial cells, some of which differentiated into goblet cells, while others developed a 'columnar' cell morphology. The following differences between squamous- and non-squamous cultures were observed. Squamous epithelium showed self-sustained growth, while growth of non-squamous epithelial cells became self-limiting. Cytochalasin B (CB) (5 micrograms/ml for 1 h) induced contraction of the whole cell sheet of non squamous cells, but of only individual squamous cells. Squamous cell outgrowth was observed from tissues derived from fetuses of all ages (13-day fetuses through to 3-week-old rats); whereas non-squamous epithelial outgrowth was poor when rats older than the 21st gestational day were studied. These results indicate that cultures established in this manner developed the general characteristics of the cells of the organ from which they were derived, even when undifferentiated fetal tissue was used. The growth conditions needed for columnar epithelium are more stringent than those needed for squamous tissues. This technique opens the way for further characterization of growth requirements of gastrointestinal columnar epithelium. PMID- 4029265 TI - Measurement of cell proliferation in microculture using Hoechst 33342 for the rapid semiautomated microfluorimetric determination of chromatin DNA. AB - We report the development and characterization of a semiautomated method for measurement of cell proliferation in microculture using Hoechst 33342, a non toxic specific vital stain for DNA. In this assay, fluorescence resulting from interaction of cell chromatin DNA with Hoechst 33342 dye was measured by an instrument that automatically reads the fluorescence of each well of a 96-well microtiter plate within 1 min. Each cell line examined was shown to require different Hoechst 33342 concentrations and time of incubation with the dye to attain optimum fluorescence in the assay. In all cell lines, cell chromatin enhanced Hoechst 33342 fluorescence was shown to be a linear function of the number of cells or cell nuclei per well when optimum assay conditions were employed. Because of this linear relation, equivalent cell doubling times were calculated from growth curves based on changes in cell counts or changes in Hoechst/DNA fluorescence and the fluorimetric assay was shown to be useful for the direct assay of the influence of growth factors on cell proliferation. The fluorimetric assay also provided a means for normalizing the incorporation of tritiated thymidine ( [3H] TdR) into DNA; normalized values of DPM per fluorescence unit closely paralleled values of percent 3H-labelled nuclei when DNA synthesis was studied as a function of the concentration of rat serum in the medium. In summary, the chromatin-enhanced Hoechst 33342 fluorimetric assay provides a rapid, simple, and reproducible means for estimating cell proliferation by direct measurement of changes in cell fluorescence or by measurement of changes in the normalized incorporation of thymidine into DNA. PMID- 4029266 TI - Human brown adipose cells in culture. AB - Brown adipose tissue (BAT), obtained from the axillary and perirenal regions of newborns 24-48 h after death, was digested with collagenase and the free cells were cultured. Only the cultures of cells from tissue obtained later than 24 h post mortem were successful. These cells grew slowly to reach confluence. Their typical mitochondria gradually disappeared, being replaced by untypical mitochondria. After confluence, the cells accumulated large amounts of lipid in non-coalescent multivacuolar depots. This model can be useful for the study of the metabolic and morphological features of human brown fat cells. PMID- 4029267 TI - Expression of the 2-5A system during the cell cycle. AB - To determine whether the 2-5A system has a role in the regulation of cell growth we have examined all constituents of the 2-5A pathway in mouse embryo fibroblasts undergoing one cycle of division at the tertiary stage under conditions where a high degree of uniformity is maintained within each stage of the cycle. Levels of the 2-5A synthetase increased up to tenfold late in S phase and declined as cells moved through G2. A similar but smaller increase in the 2-5A-dependent ribonuclease was observed, whereas activity of the 2'5' phosphodiesterase was highest in quiescent cells. At the time of maximum synthetase levels no phosphorylated 2-5A could be detected in the intact cell. Endogenous interferon (IFN) was found in the culture supernatants in increasing concentration with cell cycle progression and addition of antibodies to IFN reduced the increase in synthetase seen in late S. Treatment of cells with a growth inhibitor that cells produce also affected synthetase activity. PMID- 4029268 TI - Flow-cytometric detection of changes in the fluorescence emission spectrum of a vital DNA-specific dye in human tumour cells. AB - A multiparameter flow cytometric technique has been used to detect changes in the emission spectrum of the DNA-specific fluorochrome Hoechst 33342 during uptake by intact, human tumour cells and during the in vitro titration of permeabilized cells. The spectral shift phenomenon was associated with changes in dye: DNA ratio revealing heterogeneity in dye-binding sites. The degree of spectral shift was sensitive to changes in pH within the physiological range. Surprisingly, chromatin structure, in terms of DNase accessibility, was not a major factor in the generation of the spectral shift. The technique of fluorescence emission analysis permits cells with similar DNA contents to be distinguished on the basis of changes in the microenvironment of chromatin for both fresh and freezer-stored biopsy or experimental preparations. PMID- 4029269 TI - Mechanism for electrosilent Ca2+ transport to cause calcification of spicules in sea urchin embryos. AB - Embryos of the sea urchin, Hemicentrotus pulcherrimus, kept in sea water containing the calcium antagonists, diltiazem and verapamil, or an anion transport inhibitor, 4,4'-diisothiocyano-2,2'-disulfonic acid stilbene (DIDS), during a developmental period between the mesenchyme blastula and the pluteus corresponding stage, became abnormal plutei with poorly developed arms and quite small spicules. Treatment with ethacrynic acid and furosemide, inhibitors of chloride transport, during the same period of development yielded quasi-normal plutei with poor spicules and somewhat developed arms. In late gastrulae, the inhibitory effects of these calcium antagonists and DIDS on the uptake of 45Ca2+ in whole embryos were as strong as those on 45Ca deposition in spicules, whereas the effects of chloride transport inhibitors on calcium deposition in the spicules were markedly stronger than on its uptake in whole embryos. Electrosilent uptake of Ca2+ seems to be established mainly by coupled influx of chloride in the cells which mediate spicule calcification, and by concomitant influx of anions in the other cells. In swimming blastulae, 45Ca2+ uptake was inhibited by calcium antagonists and DIDS, but not by chloride transport inhibitors. Ca2+ uptake probably becomes coupled with chloride influx only in embryos in which spicule calcification occurs. PMID- 4029270 TI - Cultured astrocytes form a syncytium after maturation. AB - The formation of functional gap junctions between astrocytes was investigated during differentiation of these cells in culture. Precursor cells of GFA (glial fibrillary acidic) protein-positive astrocytes were cultured in a chemically defined medium as a homogeneous population. These cells were rarely coupled to one neighbour, as revealed by electrical and dye coupling and never formed a large syncytium, as investigated by injection and spread of Lucifer Yellow. Differentiation with respect to GFA protein accumulation can be induced in these cells by culturing in horse serum-containing medium. The formation of functional junctions developed within 2 weeks in about 20% of the cells. Coupled cells formed a large syncytium. When the astrocytes were co-cultured with primary cerebellar cells (consisting predominantly of small neurons) after the switch to serum-containing medium the percentage of coupled astrocytes increased to about 65%. Again the coupled cells formed a large syncytium. Since no physical contact was possible between the astrocyte cultures and the primary cerebellar cells the stimulation of coupling had to be signalized by soluble factor(s). PMID- 4029271 TI - Selective expression of histone genes in mouse-human hybrid cells. AB - Mouse-human hybrid cells preferentially segregating mouse chromosomes contain predominantly human histone mRNAs and synthesize human histone proteins. In contrast, hybrids segregating human chromosomes contain both human and murine histone mRNAs, yet synthesize only mouse histone proteins. These results suggest transcriptional control of histone gene expression in hybrids segregating mouse chromosomes and post-transcriptional regulation in hybrids segregating human chromosomes. PMID- 4029272 TI - Phagocytic behavior of the predatory slime mold, Dictyostelium caveatum. Cell nibbling. AB - The predatory slime mold, D. caveatum, feeds upon other amoebae by phagocytosis. The D. caveatum amoebae begin feeding upon cells the same size or larger by nibbling pieces of cells. While feeding upon other amoebae as opposed to bacteria, they increase in size. This behavior resembles that of phagocytes in higher organisms. A novel method was used to follow the time course of phagocytosis. A lytic toxin, phallolysin, and mutants resistant to the toxin were utilized in an assay to separate the phagocytes from the prey cells. Since a broad spectrum of cells are sensitive to the toxin, the method has general applicability. PMID- 4029273 TI - Polysaccharides sulfated at the time of gastrulation in embryos of the sea urchin Clypeaster japonicus. AB - Based on the fact that the development of sea urchin embryos is arrested at the blastula stage in sulfate-free sea water (SFSW), we attempted in the present study to elucidate the nature of sulfated polysaccharides (PSs) which appear at the time of gastrulation in embryos of the sea urchin Clypeaster japonicus. Electrophoretic analysis of PSs prepared from embryos at different developmental stages revealed that three kinds of PSs (3A, 3B, 3C) appear de novo at the gastrula stage, and that these PSs are not found in embryos at the hatching blastula stage, nor are they found in permanent blastula reared in SFSW. These, three PSs were mostly of extracellular matrix origin. Among them, 3C was identified as dermatan sulfate on the basis of its electrophoretic mobility and sensitivity to enzymatic digestion. 3A and 3B remained to be identified. Further, a plausible precursor of 3C, which was sulfated under normal conditions, was detected as 6D in the embryos reared in SFSW. Autoradiographic analysis using [35S]sulfate revealed that these three PSs, accounted for more than 90% of [35S]sulfate incorporated into the acid PS fraction during gastrulation. PMID- 4029275 TI - In situ localization of actin mRNA in Dictyostelium discoideum aggregates. AB - By in situ hybridization of a labeled cloned DNA to cellular RNA, we have studied the distribution of actin mRNA in differentiating Dictyostelium discoideum aggregates. In migrating pseudoplasmodia, the mRNA is distributed uniformly. However, in culminating aggregates (sorogens) actin mRNA is enriched in stalk cells and in the cells at the anterior tip. Thus, the preferential synthesis of actin in prestalk and stalk cells, previously reported, is due at least partially to increased levels of actin mRNA. PMID- 4029274 TI - Analysis of the expression of the 4F2 surface antigen in normal and neoplastic fibroblastic human cells of embryonic and adult origin. AB - 4F2 monoclonal antibody recognizes a 120-kD glycoprotein on the surface of human spread fibroblastic cells of embryonic and neoplastic origin, but it does not bind to normal spread adult fibroblasts. Flow cytometric analysis reveals that human adult fibroblasts become 4F2-positive when they are analyzed as round shaped cells; this means that, in normal adult cells, 4F2 antigen behaves as a cryptic molecule. Thus, the basic difference between embryonic, neoplastic and normal adult cells consists in a different organization in the architecture of the cell membrane, since in embryonic and neoplastic cells there is a continuous expression of the 4F2 antigen independently of the cell shape and cell cycle phase. Quantitative flow cytometry shows that the mean surface density (MSD) of the 4F2 antigen 1, does not vary as a function of the cell cycle; 2, is inversely related to cell size and "metabolic time". This suggests that at the plateau phase the surface organization of G1 resting cells changes as a function of the number of days spent in culture; and 3, sarcoma and SV40-transformed cells show significantly increased MSD levels of the 4F2 antigen in comparison with normal cells of similar size. Electrophoretic analysis under reducing conditions confirms the quantitative differences in the expression of the 4F2 antigen described with the cell sorter. It also reveals, in a way different from that previously found with lymphoid cells, the coexistence of two molecules (85 and 73 kD) in the heavy chain regions. The 73 kD is, however, much more strongly expressed in the fibrosarcoma than in the embryonic cells. Finally, it shows that 4F2 antigen is a very useful tool for studying the organization and the structure of the cell membrane of human fibroblasts and can provide new insights to understand better the developmental and transformation processes. PMID- 4029276 TI - A platelet factor stimulating the proliferation of vascular endothelial cells. Partial purification and characterization. AB - Platelets have been shown to contain a novel growth factor that stimulates the proliferation of vascular endothelial cells in vitro. The factor potently stimulated both DNA synthesis and proliferation rate in serum-deprived endothelial cells. Gel exclusion chromatography showed at least two peaks of activity on endothelial cells, the major peak being at an apparent molecular weight of 20 000. Isoelectric focusing revealed that the pI of the factor was 4.0 4.8. It was adsorbed to a column of DEAE ion exchange chromatography and eluted with a salt gradient. The factor was heat-labile and trypsin-sensitive. The activity was not destroyed by a reducing agent including dithiothreitol. This factor stimulated the proliferation of vascular endothelial cells but was found to be inactive against normal rat kidney fibroblasts. PMID- 4029277 TI - Changes in phosphoprotein pattern in Schizosaccharomyces pombe. AB - A variety of evidence suggests that protein phosphorylation (pp) may be important in cell-cycle control. Phosphorylated proteins from S. pombe have been examined for phosphorylation changes under several conditions: known triggers of the division control (low nitrogen, low phosphate), cell size mutants (WEE1 and CDC2 alleles) and cell cycle mutants (CDC2, CDC10, CDC17, CDC25 alleles). Three major phosphorylated proteins (pp38, pp45 and pp54) showed the greatest response to nutritional shifts. The changes in the phosphorylated states of these proteins correlated with growth rate. Some phosphorylations (e.g. pp53) occurred transiently following a stimulus to cell division suggesting a possible involvement with the division mechanism. An allele-specific alteration of charge was noted for pp45 suggesting that this protein is the product of the CDC2 gene. The wee1-6 phosphoprotein pattern is similar to wild-type indicating that this mutant cell line accurately senses its nutritional environment and that the mutation likely affects the transfer of this information to the division control. Cells blocked by various temperature-sensitive cell cycle mutants did not show an alteration of phosphoprotein pattern. PMID- 4029278 TI - Discontinuous RNA and protein synthesis and accumulation during cell cycle of Ehrlich ascites tumour cells. AB - The cell cycle-related synthesis rate and accumulation of RNA and protein were studied in in vivo growing Ehrlich ascites tumour cells. After pulse-labelling in vivo, cell fractions from various parts of the cell cycle were obtained by means of elutriator centrifuging. The RNA synthesis rate increased three times during G1 and remained unchanged throughout the remaining part of the cell cycle. The content of RNA increased discontinuously during G1/early S phase and late S phase/G2, by a factor of about 3. The protein synthesis rate increased by a factor of 2.5 and the protein content doubled, both parameters discontinuously as found for the RNA content. On the other hand, the cellular volume increased continuously throughout the cell cycle and thus no close correlation between cellular volume and protein content was indicated by our results. A possible variation in the degradation rate of RNA during cell cycle is also discussed. The close relationship between RNA content and protein synthesis during cell cycle indicates regulation of protein synthesis at the transcription level. PMID- 4029279 TI - The effect of monensin on cell aggregation of normal and dystrophic human skin fibroblasts. AB - Measurements of aggregation kinetics using couette viscometry show that freshly trypsinized skin fibroblasts from patients with Duchenne muscular dystrophy have values of intercellular adhesiveness approx. 40% those of normal cells. If cells are allowed to recover from the effects of trypsinization (by incubation for 2 h at 37 degrees C in serum-containing medium) the intercellular adhesiveness of both cell types increases, and normal and Duchenne cells aggregate to the same extent. Exposure to the ionophore monensin during the recovery phase leads to suppression of recovery in both cell types, and this effect of the drug is greater in Duchenne fibroblasts. These results are discussed in relation to other data on the reported differential effects of trypsin and monensin on normal and Duchenne fibroblasts. PMID- 4029280 TI - Light scattering of normal human lens. III. Relationship between forward and back scatter of whole excised lenses. AB - Twenty-three human lenses from age 3-76 years were studied. Lenses obtained 24-36 post-mortem were exposed to monochromatic light (435.8 and 546.1 nm) in the I parallel and I+ modes and to white (tungsten lamp) unpolarized radiation. The light scattering intensities were obtained as a function of scattering angles from 0 to 135 degrees. The scattering intensities in the forward directions are greater than in the back scatter in all modes of illuminations. The age dependence of a number of light scattering parameters such as percent transmission; I theta/Io; dissymmetry and depolarization were obtained using regression analysis. These parameters may serve as standards of normal lenses to which similar parameters of cataractous lenses can be compared. Relationships between back scatter and forward scatter have been established using the regression coefficients. Thus, the light scattering intensity observed in the slit lamp (at 135 degrees back scatter) can be quantitatively related to the light reaching the retina at different angular displacements. PMID- 4029281 TI - Effect of adriamycin on experimental proliferative vitreoretinopathy in the rabbit. AB - The cell injection model of proliferative vitreoretinopathy (PVR) in the rabbit was used to study the therapeutic value of intravitreal adriamycin (doxorubicin). Adriamycin in a dose of 10 nmol per eye, if injected at the same time as the cells, controls PVR. At the cell doses used, PVR is not affected if there is a time interval between cell and drug injection. Because of retinal toxicity, as evidenced by electroretinographic and histopathologic changes, the beneficial effects of adriamycin on membrane formation cannot be exploited at this time. PMID- 4029282 TI - Characteristics of 45Ca uptake by the rabbit lens. AB - Lens 45Ca uptake was shown to increase when the external calcium concentration was less than 1 mM, suggesting that calcium ions themselves are able to interact with lens membranes in a way that influences the mechanism of calcium permeability. Strontium ions, added to a calcium-deficient bathing solution, were shown to attenuate the increased 45Ca uptake by the lens. There was no evidence for extracellular binding of calcium. Lens membrane permeability to calcium appeared not to be voltage-dependent since 45Ca uptake was not affected when the lens was depolarized by high potassium solutions. Calcium channel blockers were shown not to reduce the increased calcium leak resulting from exposure of the lens to a calcium-deficient medium. PMID- 4029283 TI - Role of hydrogen peroxide in riboflavin-sensitized photodynamic damage to cultured rat lenses. AB - Previous reports have differed on whether hydrogen peroxide or free radicals are the principal toxic species responsible for photodynamic damage to intact lenses cultured in medium with riboflavin, light and oxygen. To differentiate between hydrogen peroxide and free radicals, TC-199 medium containing 50 microM riboflavin was incubated in visible light prior to adding the lenses. After 4 hr the medium was placed in the dark, rat lenses, [3H]-choline and 86Rb were added, and the lenses were cultured for 4 hr. Damage to the lenses was evaluated by measuring the accumulation of choline and Rb. Lenses cultured in previously irradiated medium accumulated less choline and Rb than lenses in control medium, indicating that in the presence of light, riboflavin generates a stable factor which is toxic to lenses. The lens damage was similar to that caused by direct exposure of lenses to riboflavin and light for 4 hr. This toxicity was blocked by catalase, and was presumed to be caused by hydrogen peroxide. Because of their short lifetime in solution, photochemically generated free radicals could not have been present in the dark after the lenses were added. Rose bengal, a photosensitizer which is thought to form singlet oxygen, did not generate a stable toxic factor in the culture medium and damaged lenses only if they were present during the exposure to light. The hydrogen peroxide concentration in riboflavin-containing medium after 4 hr exposure to light was approximately 200 microM, whereas rose bengal generated less than 10 microM hydrogen peroxide.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4029284 TI - Light scattering of whole excised human cataractous lenses. Relationships between different light scattering parameters. AB - The light scattering intensities of 27 cataractous human lenses were obtained as a function of scattering angle. Unpolarized white light (tungsten) and polarized light of Hg lamp at 435.8 and 546.1 nm were used in the I parallel and I+ modes. Selected light scattering parameters such as relative scattering intensities (I45/I0), dissymmetry ratio (I135/I45) and depolarization ratios (I45/I0)+/(I45/I0) parallel were correlated with the age of lens with percent transmission using regression analysis. Excess scattering functions were calculated that quantitatively describe the quality of lens. These excess functions were also correlated with other scattering parameters. A method which can be used to estimate the light intensity that reaches the retina at different scattering angles for a cataractous lens once the back scatter intensity (slit lamp examination) is known is given. PMID- 4029285 TI - A morphologic and morphometric analysis of the aqueous outflow system of the developing cat eye. AB - The cellular and tissue changes accompanying the development and growth of the aqueous outflow system of the cat were investigated by quantitative light microscopy and by scanning and transmission electron microscopy. As in primates, the trabecular beams and sheets of the cat aqueous outflow system developed by reorganization of cells and extracellular matrix within the tissue filling the anterior chamber angle recess. Enlargement and coalescence of intercellular spaces gave rise to intertrabecular channels. From 3 to 9 days after birth, communications were established between the anterior chamber and intertrabecular spaces by perforation and resorption of tissue which initially covered the angle apex and appeared to be a peripheral extension of Descement's membrane and the corneal endothelium. Macrophage-like cells could be involved in this process. A rapid increase in the volume of the intertrabecular spaces and in the number of trabecular cells coincided with the opening of the trabecular meshwork to the anterior chamber. The trabecular meshwork grew 150-fold in volume from birth to adulthood, mainly as a result of a similar-fold expansion of its connective tissue components. The volume of the intertrabecular spaces increased 24-fold and trabecular cell number increased 14-fold during this same period. The disproportionate increase in volume of the various components of the trabecular meshwork was responsible for the decreased cell density and rarefaction displayed by this tissue as development progressed. Development of the aqueous outflow system of the cat is thus a complex, but highly co-ordinated, process, that depends on continued proliferation of cells and extracellular matrix, a progressive ordering of these components, and selective atrophy and removal of specific tissue components. PMID- 4029286 TI - The photolysis of lens fiber membranes. AB - Calf lens fiber membranes were photolyzed in the presence and absence of sensitizers and scavengers. Photolytic damage was assessed by SDS-polyacrylamide gel electrophoresis, UV and fluorescence spectra and amino acid analyses. With irradiation, there is an apparent polymerization of the major membrane polypeptide (MP26) and the formation of material which does not enter SDS polyacrylamide gels. Some degradation was also observed. These changes are accompanied by losses of histidine and tryptophan and changes in the UV spectra. The rate of photolysis is enhanced in the presence of the glucoside of 3 hydroxykynurenine (3-OH-KYN), a compound endogenous to the lens. The reaction is retarded in the presence of sulfhydryl-containing compounds such as glutathione. PMID- 4029287 TI - Cataracts in the Royal College of Surgeons rat: evidence for initiation by lipid peroxidation products. AB - The Royal College of Surgeons (RCS) rat has been extensively studied as a model system for inherited retinal degeneration. As in a number of human retinal degenerative diseases, posterior subcapsular cataracts (PSC) are associated with the retinal changes. It has been hypothesized recently that such cataracts may be initiated by toxic products generated by the peroxidation of polyunsaturated lipid components from degenerating photoreceptor outer segments. In the present study, the possibility that such a mechanism might be responsible for cataract initiation in the RCS rat has been investigated. The degeneration of the rod outer segments (ROS) occurs rapidly in these animals, beginning a few weeks after birth. Due to the failure of the retinal pigmented epithelium to phagocytize normally, ROS degeneration is accompanied by an accumulation of debris in the eye. During the brief period of maximal debris accumulation there is a marked increase in lipid peroxidation products in the vitreous. Cataract formation is correlated temporally with these events, becoming evident immediately following the time during which peroxidation products are present in the vitreous. In addition, the primary damage detected in the RCS lenses is an increase in the passive permeability of the lens membranes. Similar lens damage has been found in studies in which normal rat lenses were exposed to degenerating ROS in vitro. These findings are consistent with the hypothesis that cataracts in the RCS rat may be initiated by toxic lipid peroxidation products. PMID- 4029288 TI - Purification and characterization of two vascular endothelium effectors from fetal bovine retina, vitreous and serum. AB - The purification and characterization of uridine and thymidine, two previously isolated vascular endothelium effectors, are described. These two effectors were purified from all dialyzable fractions of fetal bovine serum (FBS), vitreous, and retina. The present study demonstrates the stimulatory characteristic of uridine and thymidine on the proliferation of aortic endothelial cells. The stimulation appears to link to their utilization by the cells in a dialyzed FBS-dependent manner. In the presence of optimal concentrations of uridine (10 microM), thymidine (0.8 microM), and dialyzed FBS (3 mg ml-1), a markedly enhanced vascular endothelial cell proliferation is attainable; uridine and thymidine alone had no significant stimulatory effect. The presence of both nucleosides, however, increased the concentration of dialyzed FBS required for half-maximum proliferation activity of fetal bovine aortic endothelial cells and also increased maximum activity. Studies with fetal bovine aortic endothelial cells showed that the activity of uridine kinase in the cells was activated by dialyzed FBS, but not by uridine and thymidine. Uridine and thymidine exerted no marked stimulatory effect on Balb/c 3T3, Swiss 3T3, and SV-T2 as noted with endothelial cells. The significance of the present findings to the proliferation of vascular endothelial cells in the retina is discussed. PMID- 4029289 TI - In vitro functions of stromal cells from human and mouse bone marrow. AB - Human fibroblastoid cell strains obtained from primary bone marrow cultures and continuous stromal cell lines recently derived from mouse bone marrow were studied. The incidence of fibroblastoid precursors (CFU-F) varied considerably in human bone marrow samples, and no differences could be detected between marrows from a group of myelodysplastic patients (age range 70-82 years) and groups of age-matched controls or younger individuals. A lack of direct correlation between initial clonogenicity and ultimate capacity of fibroblastoid cells to grow in continuous culture was observed in both the normal and the myelodysplastic groups. Despite the apparently normal clonogenicity of CFU-F in patients with myelodysplastic syndromes, some of these marrows failed to grow when subcultured. Normal fibroblastoid cells at 10(4) per culture exhibited myelopoietic activities when cocultured with fresh bone marrow cells. At higher concentrations, these cells inhibited myeloid colony formation. Fibroblastoid cells from only one out of four myelodysplastic patients examined exhibited comparable inhibitory activity. The specificity of the inhibitor(s) was demonstrated by the lack of effect of fibroblastoid cells from normal human bone marrow on the clonogenicity of mouse erythroleukemia cells. Moreover, human foreskin fibroblasts were devoid of such inhibitory activity. These functions of cultured stromal cells may correlate with some of their activities in the bone marrow microenvironment. PMID- 4029290 TI - Effects of androgen on transient endogenous spleen colonies and other hemopoietic stem cells in mice. AB - To clarify the effects of androgen on hemopoiesis in mice, we investigated changes in hemopoietic stem cells at various stages of differentiation after injection of 19-nandrolone decanoate (19-ND). 19-ND induced (a) a marked increase in the population of CFUe, especially in the spleen, and (b) a less significant increase in the number of CFUs, GM-CFC, and BFUe. The number of endogenous spleen colonies developed transiently on day 4 after irradiation (TE-CFU) increased significantly, and the initiation and induction of erythropoietic maturation was enhanced. Growth of the pluripotent stem cells (CFUs) assessed by endogenous spleen colony formation was influenced more than was the population size. Production of erythropoietin (Ep) in mice was not affected by the treatment with 19-ND. These results indicate that 19-ND affects mature precursors in erythroid cell lineage rather than pluripotent stem cells and that the effect is unlikely to be induced through an increase in the production of Ep. PMID- 4029291 TI - Murine eosinophil granulocyte proliferation kinetics in acute and chronic eosinophilia. AB - Eosinophil proliferation kinetics have been determined by examining fraction labeled mitoses (FLM) curves in femoral marrow of mice stimulated for eosinophil production. Mice with marrow eosinophilopoiesis increased as a result of infection with the parasite Schistosoma mansoni exhibited eosinophil cycle durations of 22 h. This time is not different from normal rates of murine eosinophil cell cycles. Acutely stimulated mice, however, with a rapid eosinophilia initiated by rechallenge with a soluble schistosome egg antigen preparation, had marrow eosinophil proliferative cycles of about 10 h. The long duration of eosinophil cell cycles in mice with an extensive commitment to the production of large numbers of eosinophil granulocytes suggests that several mechanisms regulate expansions of eosinophil granulocytopoiesis in vivo by hemopoietic marrow. PMID- 4029292 TI - Long-term perturbation of hemopoiesis after moderate damage to stem cells. AB - Hematological indices of BDF1 mice characterizing regeneration in a complex fashion (peripheral cell counts, bone marrow CFU-S, GM-CFU, CFU-F, and the turnover state of bone marrow CFU-S) were followed periodically for 11-14 weeks after 0.5 Gy acute gamma irradiation in order to obtain detailed information about the nonsteady state of murine hemopoiesis after moderate damage to stem cells, demonstrated in our previous experiments. Virtually complete hematological regeneration was followed by long-term increase in the proliferation rate of CFU S, oscillation in some parameters (granulocyte count, CFU-S level) or an overshooting, sometimes multiwavelike regeneration in others (reticulocyte count, thrombocyte count, and GM-CFU and CFU-F levels). These data suggest a long-term perturbation of hemopoiesis and its environment after moderate damage to the bone marrow. PMID- 4029293 TI - Size and density characterization of human committed and multipotent hematopoietic progenitors. AB - Physical characterization of human blood and bone marrow (BM) hematopoietic precursors is necessary for the design of adequate techniques to isolate these cells for experimental and possible clinical use. Elutriation and continuous Percoll gradient were used to define the size and density of committed (CFU-GM, BFU-E, and CFU-E) and multipotent (CFU-MIX) progenitors on paired BM and blood samples from normal donors. Cells were initially prepared over Ficoll-Hypaque (specific gravity 1.077 g/cm3). Elutriation was performed on a Beckman JE-6B rotor with a standard chamber at 2000 rpm using flow rates of 7-23 ml/min. Percoll gradients were centered at 1.070 g/cm3 using ultracentrifugation. Cell density was determined using marker beads. Density was slightly higher for BM than for blood progenitors of the same class. Progenitor sizes (proportionate to elutriation flow rate) were similar in BM and blood. CFU-MIX, BFU-E, and CFU-GM coseparated in blood and BM; CFU-E (BM) were larger and more dense than other BM progenitors. BM and blood E-rosette-positive cells were separated more effectively by size than by density. The similarity in size and small differences in density between blood and BM progenitors may allow adaption of blood separation techniques (apheresis) to processing of BM for cryopreservation and/or in vitro treatment. Similarly, the ability to separate T cells from progenitors in blood by elutriation (albeit only partially), as has been described for BM, may help in the modification of existing apheresis techniques to achieve such separations. PMID- 4029294 TI - Tritiated thymidine incorporation into canine cyclic hematopoietic bone marrow in vitro. AB - To investigate changes in the proliferative activity of bone marrow cells in canine cyclic hematopoiesis, nonadherent cells were incubated for 1 h with tritiated thymidine either immediately after the cultures were established or following an 18-h preincubation period. The data suggest that changes in thymidine incorporation show a 12- to 14-day cycle that consists of two distinct phases. During the first six days of the cycle (from peripheral neutropenia to relative neutrophilia), two peaks of incorporation were observed. During the second phase (corresponding to the neutrophilia and oncoming neutropenia), thymidine incorporation was uniformly lower than control values. The change from an apparently cyclical process to a low stable value occurred after the wave of marrow myelopoiesis and close to a time point (days 8-10 of the cycle) at which we have recently suggested significant changes in cell release and/or proliferation take place. The data can be interpreted in the context of a periphery-to-stem-cell feedback loop through an intermediate cell population, probably of myeloid precursors. PMID- 4029295 TI - Effects of marrow storage at 4 degrees C on the subsequent generation of long term marrow cultures. AB - The present study was undertaken to examine the effect of marrow preservation at 4 degrees C on subsequent long-term culture, which evaluates both hematopoietic precursor cells and hematopoietic microenvironmental cells. Storage of unfractionated marrow was superior to storage of buffy-coat cells in tissue culture medium with 20% fetal calf serum. CFU-C recovery in unfractionated marrow was 48.4% at four days and 21.4% at seven days. Long-term marrow cultures from cells stored at 4 degrees C for up to seven days produced CFU-C for up to seven weeks and established confluent marrow stromal cell layers. Suspension cultures of marrow cells preserved at 4 degrees C for seven days cultured with irradiated allogeneic marrow stromal cell layers from normal long-term marrow cultures showed significantly increased CFU-C production from week 2 to week 5 when compared with the control cultures without adherent cell layers. These data suggest that marrow storage at 4 degrees C for up to seven days preserves early hematopoietic precursor cells and microenvironmental cells and may be used for autologous rescue from marrow ablative therapy. PMID- 4029296 TI - Detection of nonrandom clustering of colonies in agar culture. AB - We report a quantitative method for the detection of clustering in agar cultures. A statistical model was constructed on the assumption that colony formation by a cell in agar culture was independent of its spatial relationship to other cells in the culture. Deviation from this model was then tested by a chi-squared test of the actual observations compared with values obtained from the model. This method provides a technique that will identify interactions between cells of like or unlike type. Using a cell line with an extremely high cloning frequency, we show that the assumptions of the method are valid. Two situations are examined in which there was a suggestion of colony clustering on observational grounds. In both cases the test confirmed this impression and allowed us to analyze the possible causes of this behavior. We believe that this method will be of value in the identification of as yet unknown growth factors or cell-cell interactions. PMID- 4029297 TI - Spatial interactions in the rhesus monkey retina: a behavioural study using the Westheimer paradigm. AB - For two trained rhesus monkeys, increment thresholds for a small test-spot of 100 ms duration were determined as a function of background size, at 10 retinal eccentricities along the horizontal meridian. Typical 'Westheimer-functions' were obtained, i.e. threshold first increases with increasing background size, reaches a maximum, then decreases with further increasing backgrounds and finally reaches a plateau. With increasing retinal eccentricities, the position of the peak of the functions is shifted towards larger background sizes, indicating an increase of perceptive field centre size from 0.25 degrees at 5 degrees eccentricity to 1.5 degrees at 40 degrees eccentricity. The perceptive field centres tend to be slightly smaller in the nasal retina. Total perceptive field sizes, as indicated by the beginnings of the plateaus, increase from about 1 degree near the fovea to about 3 degrees at 40 degrees eccentricity. The perceptive field centre sizes of two human observers, tested under the same experimental conditions, closely resemble those of the monkeys. The total perceptive fields are larger in the human subjects. The retinal ganglion cells determining threshold in this experiment are most likely the broad-band cells. The agreement between the behaviourally determined perceptive field centre sizes and the receptive field centre sizes of broadband cells (measured by DeMonasterio and Gouras 1975) is excellent. The dendritic fields of P-alpha-ganglion cells, most likely the morphological substrates of the broad-band cells (Perry, Oehler and Cowey 1984) are somewhat smaller at all eccentricities.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4029298 TI - Autogenetic reflex action in tibialis anterior compared with that in soleus muscle in the decerebrate cat. AB - The regulatory actions of autogenetic reflex pathways on the mechanical properties of an ankle flexor (tibialis anterior) and an extensor (soleus) in the premammillary decerebrate cat were studied. The two muscle were isolated in the same cat and each was stretched during its separate activation. The yield in stiffness shown by areflexive muscles during stretch was largely compensated for in tibialis anterior as well as in soleus by reflex action. Resultant (total) stiffness varied by less than a factor of two over a wide range of contractile forces in the two muscles. Further, resultant stiffness increased as stretch amplitude decreased in both muscles, but the variation was less for TA. In most preparations, the resultant stiffness in soleus was significantly larger than the resultant stiffness of tibialis anterior. It is concluded that autogenetic reflexes govern the mechanical properties of both flexors and extensors. In addition, the extensor bias in the decerebrate preparation is due not only to greater activation in extensors but to a greater resultant stiffness as well. PMID- 4029299 TI - Photoreceptor inputs to cat lateral geniculate nucleus cells. AB - The spectral sensitivities of single on- and off-centre, brisk sustained and brisk transient cells recorded from the A laminae of the lateral geniculate nucleus (LGNd) in cats anaesthetised with nitrous oxide and oxygen supplemented with halothane were measured under photopic and mesopic achromatic adapting conditions. All cells possessed spectral sensitivity functions with a single peak at about 556 nm under photopic conditions. Intense chromatic adapting fields superimposed on the photopic background affected neither the shape of the spectral sensitivity functions nor the position of the peak wavelength. Under mesopic adapting conditions cells possessed spectral sensitivities with two peaks, one at 507 nm and one at 556 nm. These results are interpreted as suggesting that the cells of the A laminae of the LGNd receive inputs from rods with maximum sensitivity at 507 nm and a single class of cones maximally sensitive at 556 nm. PMID- 4029300 TI - Excitability of reciprocal and recurrent inhibitory pathways after voluntary muscle relaxation in man. AB - We studied the potential contribution of postsynaptic mechanisms to the depression of reflex excitability which occurs immediately after a voluntary release from tonic muscle contraction. The excitability of the Soleus (Sol) motor pool was tested at rest and after voluntary muscle relaxation. In both cases the Sol H-reflex was conditioned by a single shock to the peroneal nerve, in order to activate the Ia interneurones (INs) mediating the reciprocal inhibition via a peripheral input, or by a short-lasting voluntary contraction of the Tibialis Anterior (TA) muscle, to activate the Ia INs via a central command. Changes in excitability of Renshaw cells were also tested at rest and after release, to assess the role of recurrent inhibition in the release-induced inhibition of the Sol H-reflex. It was demonstrated that: the excitability of the INs mediating the reciprocal inhibition was only slightly enhanced in comparison with resting conditions; the H-reflex of the antagonist muscle (TA) evoked after Sol release was not consistently facilitated with respect to rest; the command to contract the TA muscle reduced the H-reflex of the Sol muscle during rest but not after Sol release; recurrent inhibition did not increase its effect in the post-release period. Such features suggest that recurrent and reciprocal post-synaptic inhibitions do not play a major role in reducing the reflex excitability of a relaxing muscle; rather, the command to release prevents the reciprocal inhibitory effect which accompanies the contraction of the antagonist muscle.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4029301 TI - Cell formation in the motor nucleus and mesencephalic nucleus of the trigeminal nerve of rats made hypothyroid by propylthiouracil. AB - Neurogenesis in the motor and mesencephalic nuclei of the trigeminal nerve was examined using autoradiographic techniques. Two groups of pregnant rats (control and experimental) were injected with two successive daily doses of 3H thymidine in an overlapping series starting from day nine of gestation in order to label in their progeny, the dividing precursor of neurons of the motor nucleus and mesencephalic nucleus of the trigeminal nerve. Control group of rats was raised on a standard diet, while the experimental group was made hypothyroid by propylthiouracil (PTU). At postnatal ages ranging between 20-30 days in the pups of both the control group and experimental group, the percentage of cells labelled and the proportion of cells added during each embryonic day were determined quantitatively throughout the rostro-caudal extent for both motor and mesencephalic nuclei. The neurons of the mesencephalic nucleus undergo their final cell divisions between gestational days 9 and 10 (E9 and E10). More than 80% of the population is generated by E10. The neurons of the motor nucleus undergo their final cell divisions between E9 and E11, and nearly 88% of the cells is generated by E11. In the thyroid deficient rats, in both nuclear centers, only 61% of the cells is generated by E12, and labelled cells are observed even as late as E18 and E19. In the hypothyroid state, there is a significant lengthening of the proliferative period. On the basis of absolute datings and duration of neuron production, it is postulated that in normal development, thyroid hormone determines the duration of the proliferative period, and push cells into the differentiative phase by taking them out of the proliferative phase. PMID- 4029302 TI - Resistance to extinction after schedules of partial delay or partial reinforcement in rats with hippocampal lesions. AB - Two experimental procedures were employed to establish the reason why hippocampal lesions apparently block the development of tolerance for aversive events in partial reinforcement experiments, but do not do so in partial punishment experiments. Rats were trained to run in a straight alley following hippocampal lesions (HC), cortical control lesions (CC) or sham operations (SO), and resistance to extinction was assessed following differing acquisition conditions. In Experiment 1 a 4-8 min inter-trial interval (ITI) was used. Either every acquisition trial was rewarded immediately (Continuous Reinforcement, CR), or only a randomly selected half of the trials were immediately rewarded, the reward being delayed for thirty seconds on the other trials (Partial Delay, PD). This delay procedure produced increased resistance to extinction in rats in all lesion groups. In Experiment 2 the ITI was reduced to a few seconds, and rats were trained either on a CR schedule, or on a schedule in which only half the trials were rewarded (Partial Reinforcement, PR). This form of partial reinforcement procedure also produced increased resistance to extinction in rats in all lesion groups. It thus appears that hippocampal lesions only prevent the development of resistance to aversive events when the interval between aversive and subsequent appetitive events exceeds some minimum value. PMID- 4029303 TI - Reflex actions of muscle afferents on fusimotor innervation in decerebrated cats: an assessment of beta contributions. AB - The existence of beta innervation in many cat muscles raises the possibility that spindle afferent discharge will excite beta motoneurons, augmenting spindle afferent discharge and thereby closing a positive feedback loop. In order to evaluate the strength of such a loop through beta motoneurons and muscle spindles, the stretch responses of muscle spindle afferents from medial gastrocnemius (MG) and soleus (SOL) muscles were studied in decerebrated cats before and after dorsal root section. If a positive feedback loop were operational, the spindle afferent stretch response should be diminished following dorsal root section by an amount related to the magnitude of positive feedback. After dorsal root section, the static positional sensitivities of our MG spindle afferent sample were significantly reduced for 72% (13/18, p less than 0.05) of the afferents, and dynamic rate/length slopes were decreased for 88% (8/9) of a subset of the afferents studied. Similar reductions for 6 afferents from SOL were not found. To apportion these afferent changes to reflex excitation of either gamma or beta motoneurons, we recorded the stretch responses of gamma and alpha type fibers in the same preparation. (We assume that the population of alpha-type fibers includes beta fibers). In keeping with other reports, alpha fibers were much more responsive to stretch than gamma fibers. The mean positional sensitivity for alpha fibers (1.29 +/- 0.92 pps/mm, n = 15) was greater (p less than 0.05) than that of gamma fibers (0.49 +/- 0.93 pps/mm, n = 18). Because of these differences in sensitivity, beta motoneurons are more likely (than gamma motoneurons) to be involved in a positive feedback loop, although some gamma contribution is also likely. Using equations based on a beta position regulating scheme, differences in spindle positional sensitivity were used to estimate beta loop gain. The average loop gain was estimated to be 0.41 (n = 18). The contribution of such a beta configuration to reducing the sensitivity of muscle to changes in load and muscle properties is evaluated. PMID- 4029304 TI - Deafferentation of oculomotor proprioception affects depth discrimination in adult cats. AB - Depth discrimination was tested behaviourally in adult cats prior to and after chronic section of the ophthalmic branch of the Vth cranial nerve, that contains the majority of oculomotor proprioceptive fibers. Binocular depth discrimination was considerably impaired following either unilateral or bilateral oculomotor proprioceptive deafferentation. PMID- 4029305 TI - A comparison of the effects of superior collicular ablation in infant and adult rats. AB - Rats sustaining damage to the superior colliculus in infancy or adulthood and sham-operated controls were tested on two tasks requiring visual orienting to 'unexpected' and 'expected' stimuli, respectively. Experiment 1 measured the distracting effect of novel visual and auditory stimuli presented while the animals traversed a familiar runway. Control rats oriented to the distracting stimulus and had lengthened running times on the trials where it was presented. Rats with lesions of the superior colliculus were less distracted by the appearance of unexpected stimuli than sham operated controls but the severity of this effect depended on modality, and on age at operation. Experiment 2 examined the same animals' ability to detect and respond to a small and expected light that appeared at randomly determined positions around the perimeter of a chamber while the rat was at the centre. Filmed records and analyses of response latencies and errors showed that at low stimulus intensities, the active exploration shown particularly by infant-operated animals resulted in performance that was superior to that of adult-operated animals and, at least in terms of error rate, sham-operated controls. It is concluded that unusual behavioural strategies can explain all the differences between the animals operated at different ages. There was no evidence that novel projections from the retina were responsible. PMID- 4029306 TI - Combined grafts of the ventral tegmental area and nucleus accumbens in oculo. Histochemical and electrophysiological characterization. AB - Dissection techniques and optimal donor stages have been established for constructing an isolated intraocular model of the ventral tegmental area (VTA) accumbens system using intraocular sequential grafting. Single grafts including accumbens and VTA respectively survived and developed many organotypic features when taken from 15-17 day fetuses. Falck-Hillarp fluorescence histochemistry showed dopamine neurons and terminals in single VTA grafts, no or almost no catecholamine fibers in single accumbens grafts, and a well-developed VTA accumbens dopamine pathway in combined grafts where cell bodies in the VTA part provided the accumbens part with a rich terminal network. A similar distribution was found using immunohistochemistry with antibodies directed against tyrosine hydroxylase. CCK-like immunoreactivity had a distribution that mimicked that of the catecholamine-containing system. Enkephalin-like immunoreactivity was found both in single VTA and in single accumbens pieces as well as in both parts of the double grafts. Cells with long-duration action potentials typical of dopamine neurons discharged at approximately 8 Hz in single VTA grafts and below 1 Hz in the VTA part of VTA-accumbens double grafts. Cells in the accumbens portion of double grafts had shorter action potential durations and fired at 10-20 Hz. Haloperidol increased discharge frequency in VTA neurons with long action potential durations while apomorphine reduced discharge markedly. Antidromic activation of putative dopamine neurons in the VTA part was obtained by electrical stimulation of the accumbens part. The indirect dopamine agonist + 3 methyl-phencyclidine slowed firing rates of neurons in the accumbens part of double grafts. Taken together, the histochemical and the electrophysiological data show that the intraocular VTA-accumbens system retains several of its normal structural and functional characteristics. It is proposed that the isolated VTA accumbens projection can be used as a model to study the cellular mechanism of action of stimulant and opiate drugs of abuse. PMID- 4029307 TI - Projection of a cutaneous nerve to the spinal cord of the pigeon. I. Evoked field potentials. AB - Evoked field potentials have been recorded from the spinal cord after electrical stimulation of a cutaneous nerve in the pigeon. Four different postsynaptic negative waves (N1 to N4) could be discerned. These waves were obviously due to monosynaptic activation via the four different afferent fiber groups described for this cutaneous nerve (Necker and Meinecke 1984). Precise localization showed that large fibers project to deeper, medially located areas of the dorsal horn (near lamina IV) whereas smaller fibers project primarily to more laterally located superficial layers. A laterally recorded N-wave which was due to the activation of large fibers had a latency which indicated a disynaptic pathway. PMID- 4029308 TI - Projection of a cutaneous nerve to the spinal cord of the pigeon. II. Responses of dorsal horn neurons. AB - The responses of dorsal horn neurons to both electrical stimulation of a cutaneous nerve and natural stimulation of skin receptors have been studied in an avian species, the pigeon. Neurons located in either lamina I or lamina IV were recorded. Most lamina IV neurons had short-latency responses to electrical stimulation of a cutaneous nerve and were activated by stimulation of sensitive mechanoreceptors. This points to an input from mechanoreceptors innervated by large afferent fibers. Lamina I neurons which were usually located near the entrance zone of small fibers had longer latency responses and had often an input from several groups of afferent fibers including C-fibers. Many lamina I neurons were activated specifically by noxious stimulation. Some had an input from sensitive mechanoreceptors but possibly through an additional synapse. A few lamina I neurons responded specifically to activation of cold receptors. Some dorsal horn neurons showed segmental inhibition. Altogether, the characteristics of dorsal horn neurons in the pigeon studied so far were similar to those in mammalian species. PMID- 4029309 TI - Integration in descending motor pathways controlling the forelimb in the cat. 13. Corticospinal effects in shoulder, elbow, wrist, and digit motoneurones. AB - The effect of corticospinal volleys evoked by stimulation of the contralateral pyramid was investigated using intracellular recordings from alpha-motoneurones to forelimb muscles. Confirming and extending previous observations (Illert et al. 1977, Illert and Wiedemann 1984), short latency EPSPs within a disynaptic range were evoked by a train of pyramidal volleys in all varieties of shoulder, elbow, wrist and digit motoneurones. The amplitude of pyramidal EPSPs was sensitive to the stimulus repetition rate. Maximal amplitudes were observed around 2-4 Hz, while at 10 Hz the early EPSP was markedly reduced and the long latency EPSP abolished. The persistence of disynaptic EPSPs after a corticospinal transection in C5/C6 suggested that, for all types of forelimb motor nuclei, disynaptic EPSPs are relayed by C3-C4 propiospinal neurones (PNs) (c.f. Illert et al. 1977). The transection, however, caused a clear reduction in the EPSP of all motoneurone types. After a ventral lesion of the lateral funicle in C5/C6 interrupting the axons of the C3-C4 PNs, disynaptic (and possibly trisynaptic) EPSPs were evoked by a short train of pyramidal volleys. It is postulated that intercalated neurones in a disynaptic cortico-motoneuronal pathway also exist in the forelimb segments. Disynaptic pyramidal IPSPs were observed in most types of forelimb motor nuclei both before and after a corticospinal transection in C5/C6. At all joints, pyramidal excitation dominated in motoneurones to physiological flexors, while in extensor motoneurones mixed excitation and inhibition or dominant inhibition was common. Comparison of pyramidal effects in slow motoneurones (classified according to the after-hyperpolarization duration) to the long head of the triceps and anconeus revealed dominant excitation in the former and inhibition in the latter. It is suggested that the slow motor units in these muscles differ in their function although both muscles are elbow extensors. PMID- 4029310 TI - Rearrangements in the retino-geniculate projections of rats following ablation of the superior colliculus in infancy. AB - The superior colliculus was bilaterally or unilaterally ablated at different early postnatal ages in rats. When adult, each rat received a unilateral eye injection of Horseradish peroxidase to reveal the crossed and uncrossed retinal terminal fields within the dorsal lateral geniculate nucleus. Collicular ablation in the first seven days after birth, but not thereafter, produced a small hole or vacancy within the contralateral retinal terminal field which was occupied by an aberrant ipsilateral retinal terminal field. These rearrangements in the retino geniculate projections occurred in the caudal quarter of the nucleus dorso laterally just beneath the optic tract, solely ipsilateral to the ablated colliculus. Possible causes of the formation of these rearrangements are discussed, and similarities with other aberrant retinal projections following early damage to the visual system are considered. PMID- 4029311 TI - Neurogenic inflammation in skin blisters. AB - The histology of blisters induced in rats using dry-ice or vacuum applied to the hind limb footpad has been examined by light microscopy and indirect fluorescence immunohistochemistry for substance P like immunoreactivity. The effects of sciatic nerve stimulation on plasma extravasation as determined by estimation of Evans Blue content of blister fluid has been examined. Plasma extravasation occurs in both blister types following nerve stimulation. Plasma extravasation may be induced by substance P released from nerve terminals in the blister wall. Vacuum induced blisters have less tissue and nerve damage and therefore less of an inflammatory response, but plasma extravasation is greater in thermal blisters. Blisters serve as a useful model for the study of neurogenic inflammation. PMID- 4029312 TI - Role of intralaminar thalamus in gaze mechanisms: evidence from electrical stimulation and fiber-sparing lesions in cat. AB - Information on eye movement related activity in the internal medullary lamina (IML) of the thalamus is consistent with an IML role in the control of eye movements, or with its serving to convey information to the forebrain on impending events in the oculomotor system. Interpretation is impeded by the fact that eye movements evoked by electrical stimulation of the IML might be triggered by antidromic activation of projections to the IML from brainstem preoculomotor centers. In order to address this issue, thresholds for the elicitation of eye movements and cortical recruiting responses (as a marker for IML integrity) were studied before and after destruction of IML neuronal populations by the fiber sparing neurotoxin ibotenic acid. Experiments were performed in alert cats chronically implanted with a scleral search coil for the monitoring of eye movements and an electrode-cannula assembly that permitted threshold determinations and drug injections at the stimulating site without any movement of probes in the tissue. Drastic elevation of the threshold for cortical recruiting responses, but not for eye movements following ibotenic acid destruction of IML neurons uncomplicated by myelin damage at the site of stimulation suggests an antidromic route for eye movements elicited by IML stimulation. PMID- 4029313 TI - Retinal input to the nucleus of the optic tract of the cat assessed by antidromic activation of ganglion cells. AB - We have studied the physiological properties of ganglion cells in the retina of the cat. The experiments were designed to identify those ganglion cells which project to direction-selective cells in the nucleus of the optic tract (NOT), by demonstrating their antidromic activation at low threshold from an electrode in the NOT. These ganglion cells presumably provide the retinal drive to the optokinetic reflex. Altogether, 11 such ganglion cells were identified in a population of 578 cells studied. All 11 were W-cells, with slow-conducting axons. Five of the 11 had on-centre direction-selective receptive fields; the other 6 had a variety of receptive field patterns. Thus, on centre-selective cells form a much higher proportion of the retinal input to direction-selective cells in the NOT than of the overall ganglion cell population. However, their receptive field properties were too varied fully to account for the selectivity of NOT cells for horizontal stimulus movement. In summary the retinal input to the NOT appears to be formed principally or entirely by W-class ganglion cells, including many which are direction selective. It still seems necessary, however, to postulate, some non-retinal mechanism to account for all the receptive field properties of direction-selective NOT cells. PMID- 4029314 TI - Long term modification of cerebellar inhibition after inferior olive degeneration. AB - The long term effects of inferior olive destruction on the activities of the Purkinje cells and their target neurones in the cerebellar nuclei were studied in the rat. Careful observations were also made of motor behaviour throughout the study. Albino rats were injected with 3-acetylpyridine to produce a neurotoxic destruction of the inferior olive and then were used for acute recording experiments at 1-2 days, 5-7 days, 12-18 days, 35-38 days, 75-97 days and 230-252 days. After degeneration of the inferior olive, there was an initial period lasting for a few days, characterized by a high firing frequency of Purkinje cells associated with a very low level of activity of the neurones in the cerebellar nuclei. During this period, there was a deep depression of motor activity. A period of adaptation follows during the first month, characterized by a slow recovery of the initial firing frequency of the cerebellar units and a gradual recovery of spontaneous locomotion; nevertheless the firing pattern and motor behaviour remain abnormal. From one month on the unit activities disturbances and the motor deficiencies stabilize. The hypothesis is advanced that Purkinje cell inhibition on their target neurones, which increases during the initial period, gradually diminishes during the adaptation time, and then stabilizes to a subnormal state. PMID- 4029315 TI - Discriminative phonation in macaques: effects of anterior mesial cortex damage. AB - Lesion damage of the anterior midline hemisphere in M. mulatta results in impaired discriminative vocal activity. Destruction of the supplementary motor area (SMA) or pre-SMA greatly increases vocal response latency without similar changes in a non-vocal response. Discrimination and efficiency in performing the vocal and non-vocal responses are unaffected by this damage. The behavioral deficit reflects a specific loss in initiating vocal signals. PMID- 4029316 TI - Reciprocal Ia inhibition from the peroneal nerve to soleus motoneurones with special reference to the size of the test reflex. AB - The aim of the study was to examine the supraspinal control during voluntary movements of the foot in man, of the Ia inhibitory interneurones activated from the anterior tibial muscle and projecting to the soleus alpha-motoneurones. Previous studies have reported an increased inhibition of the soleus alpha motoneurones by a constant conditioning stimulus to the common peroneal nerve during dorsiflexion of the foot. This was interpreted as a sign of supraspinal facilitation of the Ia inhibitory interneurones. However, these results could not be reproduced in the present study. The contradictory results can probably be explained by some important methodological differences in the use of the H-reflex technique. PMID- 4029317 TI - Pattern ERG in the monkey after section of the optic nerve. AB - Electroretinographic responses (ERG) to homogeneous light flashes and to alternating gratings were recorded from either eye of monkeys in which one optic nerve had been previously sectioned. Three weeks after optic nerve section the ERG response of the operated eye to alternating gratings was drastically reduced in amplitude and 5 weeks after surgery it was reduced to noise level. The uniform field ERG was unaffected. Histological examination of whole-mounted retinas of monkeys sacrificed 6 and 8 weeks after optic nerve section showed a loss of ganglion cells in the operated eye. It is concluded that the integrity of ganglion cells is essential for the generation of a normal ERG response to gratings. PMID- 4029318 TI - The hemispheric distribution of the transient rat VEP: a comparison of flash and pattern stimulation. AB - We investigated the hemispheric distribution of the rat visual evoked potential (VEP) to pattern reversal and flash stimuli, presented monocularly at a rate of 1 Hz. Pattern VEP components could be recorded only over an area bounded by the anatomical coordinates of area 17, while some flash VEP components were recordable outside the primary visual area. Monocular pattern stimulation, as expected, evoked dominant contralateral VEPs. Surprisingly, ipsilateral responses could be also recorded with the reference electrode near the nasal bone. These VEPs showed partial polarity inversion compared to the contralateral EPs. To assess the origin of the ipsilateral EPs, we also recorded EPs following surgical deafferentation of the ipsilateral cortex. Our data reveal that ipsilateral VEPs represent volume conducted potentials. PMID- 4029320 TI - Isometric torque-angle relationship and movement-related activity of human elbow flexors: implications for the equilibrium-point hypothesis. AB - Since the moment arms for the elbow-flexor muscles are longest at intermediate positions of the elbow and shorter at the extremes of the range of motion, it was expected that the elbow torque would also show a peak at an intermediate angle provided the activity of the flexor muscles remained constant. We measured the isometric elbow torque at different elbow angles while the subject attempted to keep constant the electromyographic activity (EMG) of the brachioradialis muscle. The torque-angle relationship thus obtained exhibited a peak, as expected, but the shape of the relationship varied widely among subjects. This was due in part to differences in the variation of the biceps brachii EMG with elbow angle among the different subjects. The implications of these observations for the equilibrium-point hypothesis of movement were investigated as follows. The subject performed elbow movements in the presence of an external torque (which tended to extend the elbow joint) provided by a weight-and-pulley arrangement. We found in the case of flexion movements that invariably there was a transient increase in flexor EMG, as would seem necessary for initiating the movement. However, the steady-state EMG after the movement could be greater or less than the pre-movement EMG. Specifically, the least flexor EMG was required for equilibrium in the intermediate range of elbow angles, compared to the extremes of the range of motion. The EMG-angle relationship, however, varied with the muscle and the subject. The observation that the directions of change in the transient and the steady-state EMG are independent of each other militates against the generality of the equilibrium-point hypothesis. However, a form of the hypothesis which includes the effects of the stretch reflex is not contradicted by this observation. PMID- 4029319 TI - Enhancement of visual responses of area 7 neurons by electrical pre-conditioning stimulation of LP-pulvinar nuclei of the monkey. AB - The characteristics of visually evoked unit responses in area PG of the infraparietal lobule were studied in the awake trained Rhesus monkey. These responses are shown to be significantly modified by pairing the visual stimulus with pre-conditioning stimulation of targets in the LP Pulvinar complex. Pre conditioning stimuli were either single pulses, or a 50 ms train of pulses at 100 Hz delivered through bipolar electrodes 20 ms prior to, simultaneously with, or 50 ms following the visual stimulus. In some cases, modifications of the visual responses appeared as more massive discharges; in others they became bursts of constant latencies, pattern and duration, that contained high frequency discharges. A pre-conditioning single stimulus delivered simultaneously to a few sites in the LP, medial and lateral pulvinar was more effective than stimulation at a single electrode site, and produced an enhancement that appeared like an additive effect of several inputs. In the enhanced condition, repetition of single pulse preconditioning stimulation resulted in a considerable build-up of the enhancement. A pre-conditioning train of stimuli delivered during enhancement resulted in a further increase in the constancy of response durations and patterns. These changes, lasting as long as five minutes, manifested hysteresis: when recovery was allowed without any pre-conditioning stimulation, the various response patterns appeared in a reverse order. It is proposed that this dependence of the responses on the neural state is based on a complex network of inputs to cells of area 7. PMID- 4029321 TI - Effects of nitrous oxide on the functional characteristics of cells in the extrastriate cortex of the cat. AB - The directional preferences, receptive field areas, peristimulus-time (PST) histograms and spontaneous activities of 112 feline visual cortical (area 18) cells were studied before, during, and after the administration of nitrous oxide. These cellular characteristics were altered by nitrous oxide inhalation; some quite substantially. The data indicate that the functional characteristics of cortical visual cells, such as the receptive field and the directional preference, are variable; and, among other factors, depend also on the anaesthetic administered to the animal. PMID- 4029322 TI - Rapid goal-directed elbow flexion movements: limitations of the speed control system due to neural constraints. AB - In rapid goal-directed elbow flexion movements the influence of both movement amplitude and inertial load on the three-burst pattern and the consequences on movement time were studied. Subjects performed visually guided, self-paced movements as rapidly and as accurately as possible. An increase of both the movement amplitude and the inertial load were found to be interacting factors for the modulation of the three-burst-pattern and movement time. The first biceps burst progressively increased in duration and amplitude for larger movements, resulting in prolonged movement times. Surplus inertial loads further prolonged the agonist burst for large, but not for small movement amplitudes. The activity of the antagonist burst, in contrast, was largest in small movements and successively decreased at increasing movement amplitudes. Its duration, however, remained fairly constant. As was similarly observed for the agonist burst, surplus inertial loads lead to a prolongation of antagonist burst duration and an small movement amplitudes. It is suggested that in elbow flexion movements the programming of fastest goal-directed movements must take into account neural constraints and biomechanical characteristics of the agonist muscle and the antagonist muscle. Due to neural constraints of the biceps muscle, in contrast to finger movements, the concept of movement time invariance does not hold for elbow movements. Furthermore, neural constraints of the antagonist muscle lead to a limited force production of the agonist muscle at small movement amplitudes in order to avoid an overload of the braking process.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4029323 TI - Motor behavior underlying the control of an upside-down vertical posture. AB - The present study examines the control of equilibrium by trained acrobats standing balanced upside-down on their hands. The focus of the experiment was to analyze the postural attitudes of various body segments and the underlying motor activity, and to evaluate the influence of vision. We found a strong correlation between the motor activity of two antagonist muscles of the forearm and the anteriorposterior position of the center of gravity. The upside-down standing posture was most stable when the neck was dorsiflexed, indicating that the tonic neck reflex and the tonic labyrinthine reflex play an important role in the stability of this posture. Comparison between known data about the normal standing posture, on the feet, and the upside-down standing posture, on the hands, shows that motor behavior of the two postures is similarly organized. PMID- 4029324 TI - The relationship between feline pupil size and luminance. AB - The relationships between luminance and height, width or area of the feline pupil were investigated in awake, normal adult cats whose pupils were photographed over a range of light levels with the aid of electronic flash. The results are compared with previous measurements of pupil width and height in awake animals (Kappauf 1943); and with estimates of pupil width, height and area in lightly anaesthetised cats (Wilcox and Barlow 1975). The implications of these results for retinal illumination and colour discrimination are discussed. PMID- 4029325 TI - Action of norepinephrine in the dentate gyrus. I. Stimulation of locus coeruleus. AB - The effect of stimulating locus coeruleus (LC) on the response of dentate gyrus granule cells to medial perforant pathway stimulation was studied in anesthetized rats. Field responses were recorded simultaneously at the mid-dendritic and granule cell levels. Two types of responses were recorded: those due to the synchronous firing of granule cell action potentials (population spikes) and those produced by excitatory synaptic activity (evoked synaptic potentials or ESPs). Stimulation of LC prior to stimulating the perforant pathway resulted in a decrease in the ESP (inward current) measured at the dendrites and, in most animals, an increase of the population spike measured at the granule cell level. Although LC stimulation decreased the ESP at the dendrites, the ESP at the granule cell body level (outward current) was not affected. The changes in granule cell responses following LC stimulation are discussed in relation to previous findings in freely moving rats. PMID- 4029327 TI - The interaction of conflicting retinal motion stimuli in oculomotor control. AB - Oculomotor response has been assessed in humans during the presentation of conflicting retinal motion stimuli. In the majority of experiments a background stimulus was made to move with a constant velocity ramp in one direction followed by rapid resets at regular intervals. In the absence of an adequate fixation target this ramp-reset stimulus induced a nystagmus with a slow-phase velocity and saccadic frequency which remained almost constant as reset frequency was increased from 2 to 5 Hz. Moreover, the induced eye velocity could be considerably increased if the subject attempted 'active' matching of display velocity. During both 'active' and 'passive' responses eye velocity gain reached a peak when display velocity was between 2 degrees/s and 5 degrees/s. The presence of small stationary targets induced a suppression of the passive ramp reset response which was modified by target eccentricity and by tachistoscopic target illumination. When subjects pursued a sinusoidally oscillating target against a stationary structured background, eye velocity gain was significantly less than for pursuit against a blank background. The degree of interaction between conflicting stimuli was found to be dependent on their relative size, peripheral location and velocity. However, it appears that the human observer is able selectively to enhance feedback gain from one particular source in order to dominate stimuli from other unwanted sources. PMID- 4029326 TI - Action of norepinephrine in the dentate gyrus. II. Iontophoretic studies. AB - The effects of iontophoretic application of 1-norepinephrine (NE) and related drugs on granule cell responses evoked by a stimulus pulse applied to the medial perforant pathway were studied in anesthetized rats. Drugs were applied and responses recorded at successive dorso-ventral positions along the dendrites and at the cell body layer. 1. Reciprocal actions of alpha and beta receptors were revealed in the cell body region. The beta agonist isoproterenol decreased the population spike while the beta antagonist sotalol increased it. In contrast, the alpha agonists phenylephrine and clonidine increased the population spike whereas the alpha antagonist prazosin decreased it. The action of the drugs was rapid, dose dependent and reversible. NE itself had no effect when applied in the granule cell layer. 2. In contrast to the failure of NE to elicit a short term response, and in confirmation of a previous report (Neuman and Harley 1983), the prolonged application of NE in the granule cell layer produced a longterm enhancement of the population spike. However, this effect was also observed after the application of d-NE. 3. NE affected granule cell responses in the middle third of the dendrites where it reduced the evoked synaptic potential (ESP, current flow produced by excitatory synaptic activity) in a dose-dependent manner. Recordings taken simultaneously in the cell body region revealed a reduction of the population spike and no change in the ESP at the cell body layer (the positive-going ESP reflecting an outward current flow from the cell). In an attempt to delineate receptor specificity, a series of alpha and beta agonists and antagonists were applied to the mid-dendritic region. All drugs reduced the ESP in a manner similar to NE. Such lack of specificity in the action of NE has been previously reported in the spinal motoneuron (Engberg et al. 1976; Marshall 1983). The function of NE in the dentate gyrus is discussed in the light of these and previous results. PMID- 4029328 TI - Detection of visual stimuli in far periphery by rats: possible role of superior colliculus. AB - Previous work has been shown that rats with lesions of the superior colliculus fail to respond to distracting visual stimuli presented in the peripheral field while the animals are running towards a central stimulus. To assess how far this peripheral neglect is due to an attentional deficit, rats were trained before operation to obtain reward by running towards either peripheral or central lights that were presented when the animals' heads were stationary in a known position. Response to stimuli presented 120 deg from the midline was severely impaired after removal of the superior colliculus: the animals behaved as if they had difficulty in detecting the onset of the light. In contrast, response to stimuli 40 deg from midline was unaffected. Control lesions of striate cortex did not significantly impair performance at any position. The finding that collicular animals were impaired at responding to stimuli in the far periphery, that were not irrelevant distractors but instead predicted reward, suggests that one component of the visual neglect produced by damage to the superior colliculus in rats may be a sensory deficit in the far peripheral field. In addition, comparison with previous results indicates that training to attend to visual stimuli in more central regions does improve performance, as would be expected if the deficit were an attentional one. It is therefore argued that collicular neglect in rats should be regarded as a multicomponent impairment. PMID- 4029329 TI - Outbred Sprague-Dawley rats from two breeders exhibit different incidences of neuroanatomical abnormalities affecting the primary cerebellar fissure. AB - A significant variation in the incidence of alterations in the cellular organization along the primary fissure of the cerebellum is observed in outbred Sprague-Dawley rats obtained from Hilltop Animal Labs (89.9%) and Charles River Canada (34.1%). In this abnormality, there are areas in the depths of the primary fissure which lack pial cells, exhibit fusion of the apposing molecular layers, and contain ectopic granule cells, often with an associated disorganization of the cortical laminae. The extent and incidence of the abnormality can vary between individuals and litters, but the general incidence rate for a given breeder appears to be consistent over extended breeding cycles. This finding has serious implications for the use of outbred animals from different breeders when collecting data during the course of an experiment and when comparing and replicating data from different laboratories. PMID- 4029330 TI - Long term survival of cat retinal ganglion cells after intracranial optic nerve transection. AB - After intracranial transection of the optic nerve in cats the retinal stump of the nerve was injected with HRP. Surviving retinal ganglion cells can be retrogradely labeled at least up to 15.5 months of postoperative survival. PMID- 4029331 TI - Dynamic properties of fiber bundles from the rat sternomastoid muscle. AB - The sternomastoid muscle of the rat can be subdivided into a "white" and "red" portion. The red portion predominantly contains type IIA fibers and the white portion type IIB fibers. Fiber bundles were dissected from the two parts of the muscle and their dynamic properties determined; both showed "fast-twitch" type characteristics. Small, but significant, differences were found in their isometric properties. Their force-velocity relationships were identical, although the maximum speed of sarcomere shortening (about 40 microns s-1) was significantly less than that of other fast-twitch rat muscles. Other differences in the respective force-length relations at different temperatures were noted. The desirability of pursuing these investigations on identified single fibers is emphasized. PMID- 4029332 TI - Effects of halothane on the development of rat brain: a golgi study of dendritic growth. AB - Dendritic growth was studied in rats exposed to halothane in utero for the entire gestation period and 60 days after birth. The exposure conditions were control, intermittent halothane (25 +/- 5 ppm or 100 +/- 5 ppm, 8 h/day, 5 days/week), or continuous halothane (25 +/- 5 ppm, 24 h/day, 7 days/week). Dendritic growth in terms of branch numbers and length was most advanced in the control groups, followed by those groups exposed to 25 +/- 5 ppm halothane intermittently, 25 +/- 5 ppm halothane continuously, and 100 +/- 5 ppm halothane intermittently. The latter two exposure conditions exerted identical effects on dendritic growth. The order of this dendritic growth level established at 5 postnatal days remained the same throughout the first 95 postnatal days in both the entorhinal cortex and subiculum. The effect of halothane on dendritic growth appeared to be enduring, and the delay in the initial dendritic growth caused by halothane was not compensated for by an increased rate of dendritic growth. PMID- 4029333 TI - Effects of halothane on synaptogenesis and learning behavior in rats. AB - Synaptic density was quantitated in the entorhinal cortex and subiculum of rats at 5, 21, 34, and 95 postnatal days. These rats were offspring of mothers that had been subjected to four different concentrations of halothane during gestation and for 60 days after birth. The exposure conditions were control, intermittent halothane (25 +/- 5 ppm or 100 +/- 5 ppm, 8 h/day, 5 days/week) and continuous halothane (25 +/- 5 ppm, 24 h/day, 7 days/week). Synaptic density in rats exposed to halothane was significantly less than in control rats. Animals exposed intermittently to 25 +/- 5 ppm halothane had higher synaptic density than animals exposed continuously to 25 +/- 5 ppm halothane or intermittently to 100 +/- 5 ppm halothane. The latter two exposure conditions exerted similar effects. The lag in synaptic development was established at 5 days postnatal and remained the same throughout the first 95 postnatal days in both the entorhinal cortex and subiculum. Delayed synaptogenesis caused by halothane was indicated by the presence of growth cones in halothane-exposed rats to 34 days compared with 21 days in the control rats. The spontaneous alternation test indicated that the delayed synaptogenesis by halothane was sufficient to suppress behavioral development. Thus, the delay in the initial synaptic maturation caused by halothane exposure in utero may result in permanent morphologic and functional deficits of the brain. PMID- 4029334 TI - Dendritic alterations in chronic animals with experimental neurofibrillary changes. AB - Dendritic changes were quantitated in the cerebral cortex and subiculum of rabbits injected with aluminum tartrate for 90 days (5 days/week) at 100, 200, and 300 days after the last injection of aluminum. Both apical and basal dendrites of the cerebral cortex and subiculum responded similarly to aluminum tartrate. The dendrites were fewer and shorter in the animals examined at 200 and 300 days postinjection of aluminum tartrate. Such dendritic changes were more prominent at longer postinjection times and in dendrites that were more peripheral from the cell body. Aluminum-induced changes in apical dendrites were more prominent in the subiculum than in the cerebral cortex. Aluminum-induced changes in basal dendrites, however, were more prominent in the cerebral cortex than in the subiculum. The results suggest a time delay between the initial accumulation of neurofibrillary changes and the subsequent loss of peripheral dendritic branches, which appears to be long-lasting. PMID- 4029335 TI - Changes in membrane potential and potassium and sodium activities during postnatal development of mouse skeletal muscle. AB - Dual-channel potassium-selective and single-channel sodium-selective microelectrodes were used to investigate the cause of changes in resting membrane potential of muscle fibers of the mouse during early development. The resting membrane of extensor digitorum longus fibers hyperpolarized during the postnatal period from -41.8 mV at 4 days of age to -76.4 mV at 27 days. During this period intracellular potassium activity increased by 42.1% from 82.5 mM at 8 days to 117.2 mM at 29 days. Intracellular sodium activity was high at 8 days, 23.7 mM, but decreased rapidly to adult values by 27 days when it was 9.98 mM, a 57.9% reduction in sodium activity. The time course of the change in resting membrane potential was different from that of the potassium equilibrium potential calculated from the data. If only potassium and sodium ions were to make significant contributions to the potential, then it was calculated that the permeability ratio PNa:PK would have to change from a value of 0.0659 at 8 days to 0.0227 at 27 days. The results indicated that other factors might be involved in generating the membrane potential inasmuch as, although both intracellular potassium and sodium activities did not change significantly after 27 to 30 days, the membrane potential had not attained adult values at that time. The possibility that increases in muscle activity during the postnatal period might initiate the changes in membrane polarization and intracellular ion activities is discussed together with possible complications in interpretation due to great variations in fiber diameters. PMID- 4029336 TI - Rapid auditory evoked vascular response in man. AB - Plethysmographic signals were recorded in four body regions (fingertip, forearm, cerebral cortex, and ophthalmic artery) of normal, healthy subjects during the presentation of brief auditory tones. Tones were presented during either systolic or diastolic phases of the cardiac cycle. Using data processing techniques similar to those employed in cortical evoked potential studies, averaged waveforms were derived which revealed the presence of a polyphasic volumetric response beginning as early as 150 ms (after onset of tones) in some subjects. Grand average waveforms suggested a similar morphology in all four body regions. The rapid onset argued for neural mediation of this response which may represent a sudden, transient flexure of vascular smooth muscle. The presence of this evoked vascular response in the brain suggests a previously unreported responsiveness of the cerebral vasculature in man to simple auditory stimulation. PMID- 4029337 TI - Prenatal exposure to ethanol retards the development of kindling in adult rats. AB - The development of kindling was examined in adult rats exposed to ethanol prenatally. Pregnant Wistar rats were fed a liquid diet containing either 6.7% ethanol or pair fed an isocaloric equivalent. At birth, the litters were cross fostered to surrogate mothers. At 80 days of age, a bipolar electrode was placed either in the right basolateral amygdala or the right angular bundle of entorhinal cortex. Kindling stimulations were administered three times a day until each rat had exhibited three class 5 kindled motor seizures. The total number of kindling stimulations required to exhibit class 1 through class 5 motor seizures was significantly greater in the rats exposed to ethanol prenatally. Further, the retardation in kindling development was due to a slower progression from class 0 to class 1 kindled motor seizures. Progression between other stages was not different between the two groups. Similar results were obtained in both amygdala and angular bundle kindling experiments. Kindling is retarded in a similar fashion by partial destruction of the dentate granule cells of the hippocampal formation. Further, the pattern of dentate granule cell axonal projections to hippocampal CA3 pyramidal neurons is altered in rats exposed to ethanol prenatally. Taken together, these data suggest the possibility that a defect in the neuronal circuitry within the hippocampal formation of fetal alcohol rats may underlie a retardation in their kindling progression. This proposed defect may have functional implications related to learning deficiencies in rats and children exposed to ethanol prenatally. PMID- 4029338 TI - Acoustic facilitation of the Hoffmann reflex. AB - The facilitative effect of a pure tone on the amplitude of the Hoffmann reflex was tested in 11 subjects under four conditions: (i) trying not to respond to the tone, (ii) voluntary abduction of the right index finger in response to the tone, (iii) voluntary plantarflexion of the left leg, and (iv) right plantarflexion in response to the tone. The acoustic stimulus was a 1000-Hz pure tone (80 dB, re 0.0002 dyne/cm2), presented on a random set of trials. Tone onset occurred 100 ms prior to the electrical stimulus that evoked the Hoffmann reflex. The Hoffmann reflex was larger for "tone" trials than for "silent" trials. The facilitative effect was equal in four cases: (i) making no response (NR), (ii) finger abduction (FA), (iii) noninvolved muscle (NIM), and (iv) involved muscle during treadle pressing (IM). The effect of the first tone presented was larger than that of subsequent tones, indicating some habituation of the acoustic effect on the H-reflex. Tests for spontaneous recovery and stimulus generalization were not significant. The results supported the existence of a purely auditory facilitation of spinal excitability. PMID- 4029339 TI - Effect of electrode size on brain stimulation. AB - Behaviorally determined strength-duration curves of many brain pathways differ from those of peripheral nerves, or single fibers. The chronaxies measured using short-duration pulses are much shorter than those measured with long pulses. A suggested explanation for this was that the pathways have mixed populations of long- and short-chronaxie elements. We attempted to test this hypothesis by stimulating with electrodes of different surface area, on the assumption that they would fire different proportions of long-chronaxie elements at short pulse durations where their thresholds are high. For a given current a large electrode delivers a lower maximum current density than a small one. Electrode size was found to have no detectable effect on the shape of the strength-duration curve. An attempt to discover the characteristics needed to modulate neurons having a basically hyperbolic strength-duration curve so as to produce the empirical curve revealed that the process has a zero rheobase and is thus presumably a direct influence of current on the threshold of the stimulated axons. A probable candidate for this process is the accumulation of potassium iontophoretically driven from cells in the vicinity of the electrode. PMID- 4029340 TI - Changes in the cholinergic system of rat sciatic nerve and skeletal muscle following suspension-induced disuse. AB - Muscle disuse-induced changes in the cholinergic system of sciatic nerve, slow twitch soleus (SOL), and fast-twitch extensor digitorum longus (EDL) muscles were studied in rats. Rats with hind limbs suspended for 2 to 3 weeks showed marked elevation in the activity of choline acetyltransferase in sciatic nerve (38%), in the SOL (108%), and in the EDL (67%). Acetylcholinesterase (AChE) activity in the SOL increased 163% without changing the molecular forms pattern of 4S, 10S, 12S, and 16S. No significant (P greater than 0.05) changes in the activity and molecular forms pattern of AChE were seen in the EDL or in AChE activity of sciatic nerve. Nicotinic receptor binding of [3H]acetylcholine was increased in both muscles. When measured after 3 weeks of hind limb suspension the normal distribution of type I fibers in the SOL (87%) was reduced (to 58%) and a corresponding increase in types IIa and IIb fibers occurred. In the EDL no significant change in fiber proportion was observed. Muscle activity, such as loadbearing, appeared to have a greater controlling influence on the characteristics of the slow-twitch SOL muscle than on the fast-twitch EDL muscle. PMID- 4029341 TI - Regeneration of central nervous system axons into an acellular tube in the absence of distal tissue. AB - To differentiate between local and distant influences on central nerve regeneration, an impervious, stainless-steel cannula, 12 mm long, was placed in the path of severed axons within the corpus callosum of adult rats. The cannula was occluded for 1 week after implantation to prevent herniation of tissue into its lumen. The extracranial end of the tube was plugged with Gelfoam rather than tissue. Inflammatory cells within the tube decreased in number with time and all animals survived for the experiment's duration of 4 to 16 weeks. Some callosal axons grew into the cannula and eventually extended about 1.3 mm. After 8 to 16 weeks, the lumen of the cannula contained many unmyelinated axons, some of which formed fascicles, myelinated axons, demyelinating axons, a few oligodendrocytes, and many astrocytic processes, macrophages, and blood vessels. A striking feature was the linear orientation of cells and their processes. The distal tip of the core resembled a central nervous system explant: it included an appreciable number of growth cones, synaptic terminals embedded in a generous extracellular space, and occasional remyelinating axons. Thus, within an impervious, acellular conduit and in the absence of distal tissue, intrinsic, neuronal processes can be redirected, fasciculate, myelinate, and can regrow alongside glia and endothelium. An indwelling tube, isolating the growth from surrounding brain fluid, may permit assessment of glial, neuronal, and extracellular contributions to the directed regeneration of adult, central axons. PMID- 4029342 TI - Superposition of antidromic responses in pyramidal tract cell clusters. AB - Large-seeing-distance microelectrodes were used to record simultaneously the activity of several pyramidal tract neurons in cerebral cortex. When activated antidromically, these neurons responded simultaneously, forming a "stack" of superimposed spikes, rather than responding at different times within the 10-ms time interval during which they might be expected to respond. Using a variety of spike collision tests, we found that these individual spikes arose from separate sources and reflected the activity of individual, albeit neighboring, pyramidal tract neurons. The collaterals of neurons within a stack projected to different structures, further verifying that separate neurons were involved. Such synchrony of antidromic activity among neighboring pyramidal tract neurons is an exceedingly low-probability event, if neighboring fibers conduct independently of one another. Our results imply that fibers from small clusters of neurons in the cortex assemble to form synchronously conducting bundles of fibers within the pyramidal tract. PMID- 4029343 TI - Ornithine decarboxylase in motoneurons during regeneration. AB - The activity of ornithine decarboxylase, the rate-limiting enzyme in polyamine synthesis, was assayed in the isolated facial nucleus of the rat at various times after axotomy of the facial nerve. In addition, it was measured 24 h after the second of a series of two lesions (conditioning lesion design) with various times between the first and second operations. Ornithine decarboxylase activity was found to increase 8 h after nerve transection and was maximum after 24 h (300% of control). Thereafter the activity declined to subnormal levels where it remained for several weeks. Ornithine decarboxylase activity did not increase again when a second axotomy was made 2 weeks after the first lesion. However, ornithine decarboxylase did respond to the second axotomy if it was carried out 3 weeks after the first lesion. Histochemical localization of ornithine decarboxylase demonstrated that the increase in enzyme activity was mainly confined to the perikarya of the motoneurons. These data suggest that this enzyme is somehow involved in triggering the "regeneration program" and clearly indicate that at least some aspects of the neuronal response to axotomy are not further stimulated by a conditioning lesion. PMID- 4029344 TI - Reticular formation neurons related to tongue movement in the behaving cat. AB - We have found a number of cells related to tongue movement in the medial brain stem reticular formation of the unanesthetized cat. These cells constituted less than 2% of the cells tested in this region and were distributed throughout several nuclei in the medulla and pons including nucleus reticularis pontis caudalis, nucleus reticularis gigantocellularis, and the border between nucleus reticularis paramedianus and nucleus interfascicularis hypoglossi. All observed tongue movement cells (N = 6) fired maximally during protrusive tongue movements. One medullary cell discharged primarily during the protrusive tongue movement to the ipsilateral side, whereas no lateral preference was detected in the other cells. Gustatory and mechanosensory stimulation of the tongue was unnecessary for inducing discharge in these cells. Tongue movement-related cells shared several characteristics that differentiated them from adjacent reticular formation cells, including absence of response to startle-inducing auditory stimuli and low levels of spontaneous waking and sleep activity. In two pontine cells located near the trigeminal motor nucleus, spike-triggered averages of tongue EMG revealed a short latency (5 ms) inhibitory effect on the ipsilateral genioglossus muscle by the units' discharge. We suggest that neurons of this type might be involved in tongue-jaw coordination during mastication, licking, and grooming. PMID- 4029345 TI - Trypanosoma brucei: infectivity and immunogenicity of cultured parasites. AB - Trypanosoma brucei brucei, derived from the salivary glands of infected tsetse flies (Glossina morsitans morsitans) and maintained in culture for over 4 years, were infective to both albino rats and tsetse flies. Virulence was markedly enhanced during the first passage in albino rats or tsetse flies. Irradiated cultured trypanosomes induced immunity to homologous challenge but not to tsetse fly or blood-induced challenge with the same stock. PMID- 4029346 TI - Schistosoma mansoni: suramin and trypan blue in vitro and the ultrastructure of feeding schistosomules. AB - The in vitro effects of suramin and trypan blue on schistosomules of Schistosoma mansoni were examined by light and electron microscopy. The drugs were administered to 12-day cultures of schistosomules produced by the penetration method. The larvae were maintained on mouse red blood cells for 5 days prior to addition of the drugs. At the concentrations used, the morphological changes attributable to the drugs were identical for the two drugs. The first signs of anomaly were observable at 8 hr after exposure. At this time, the digestive system showed signs reminiscent of early starvation effects such as alterations of the Golgi and an increase of autophagy. After 36 hr, a rapid disintegration of the gastrodermis became evident. It was hypothesized that the drugs initially inhibit the digestive enzymes and, subsequently, labilize the luminal plasma membrane of the gastrodermis. By 48 hr after exposure, the larvae were dead. PMID- 4029347 TI - Plasmodium vinckei: suppression of mouse infections with desferrioxamine B. AB - Plasmodium vinckei kills NMRI mice within 6 days after infection. Treatment of infected animals with desferrioxamine B for 5 days was found to suppress the parasitemia in a dose-dependent manner. The desferrioxamine B-iron complex (DFO/Fe3+) was ineffective, which suggests that the iron-chelating capacity of free desferrioxamine B is the antimalarial principle. All mice survived when they were given 0.3 mg desferrioxamine B/g every 12 hr for 14 days after infection. In addition, they were resistant to reinfection for at least 8 weeks. Eight months after desferrioxamine B treatment, all mice had lost their induced immunity and were as susceptible to malaria as controls. These results illustrate the dependence of the malarial parasite on ionic iron and suggests new methods for the therapy of parasitic diseases. PMID- 4029348 TI - Eimeria tenella: immunogenicity of arrested sporozoites in chickens. AB - Groups of chickens were medicated with the anticoccidial drug, decoquinate, and starting 1 day after this medication they were given daily inoculations of either 1 X 10(4) (Experiment 1) or 1 X 10(5) (Experiment 2) oocysts of a decoquinate sensitive strain of Eimeria tenella. This assured the presence of large numbers of drug-inhibited sporozoites in the cecal tissues. The immunity arising from the presence of these inhibited sporozoites was assessed by challenging the medicated chickens with a 2.5 X 10(5) oocysts of a decoquinate-resistant strain of E. tenella. The response to challenge was assessed by weight gain, the severity of cecal lesions, hematocrits, and cecal oocyst numbers. The inhibited sporozoites promoted little (if any) immunity judged by clinical signs of disease. However, judged by body weight changes after challenge, the presence of inhibited sporozoites provided substantial protection against the body-weight-depressing effects of the challenge dose. These findings emphasize the importance of stage specific antigen expression in Eimeria spp. infections and support the notion that immunogenicity is associated with tropic stages of the parasite. PMID- 4029349 TI - Brugia malayi: intravenous injection of microfilariae in ferrets as an experimental method for occult filariasis. AB - Microfilaremia, immune responses, and pathology were compared in ferrets infected with 100 third-stage larvae of Brugia malayi (subperiodic strain) or injected intravenously with 10(6) microfilariae. Ferrets (Mustela putorius furo) inoculated with third-stage larvae typically became patent during the third month after infection, with a mean patency of 123 +/- 25 (SE) days. Ferrets injected intravenously with microfilariae exhibited a relatively constant microfilaremia for 3-4 weeks and usually cleared microfilariae before the fourth month. Ferrets that cleared microfilariae after intravenous injection of microfilariae or after infection with third-stage larvae failed to become patent or became amicrofilaremic within 3 weeks after a challenge intravenous injection of 10(6) microfilariae. Clearance of circulating microfilariae was associated with eosinophilia and serum antibody specific for the microfilarial sheath in ferrets injected with microfilariae and in most ferrets infected with third-stage larvae. Ferrets infected with third-stage larvae and necropsied after clearance of microfilariae had tissue inflammatory reactions to microfilariae characteristic of occult filariasis (tropical eosinophilia) in man; these ferrets exhibited immediate cutaneous hypersensitivity and circulating reaginic antibody to antigens of microfilariae. In ferrets necropsied following two intravenous injections of microfilariae, the majority of ferrets examined within 10 days after clearance of microfilariae had visible liver lesions to microfilariae identical to those of the ferrets infected with third-stage larvae; immediate cutaneous hypersensitivity and reaginic antibody were not consistently detected in ferrets injected with microfilariae. Sera from ferrets that had cleared circulating microfilariae were transferred passively into ferrets made microfilaremic by intravenous injection of microfilariae. Sera with microfilarial sheath-reactive IgG antibody titers (greater than or equal to 1:200) and microfilarial agglutination titers (greater than or equal to 1:40) rapidly cleared injected microfilariae (less than 24 hr); this serum also cleared or greatly reduced circulating microfilariae established by an infection with third stage larvae; only the IgG-containing fraction of the sera was active in immune clearance. Sera that cleared microfilariae of B. malayi did not clear circulating microfilariae of Dirofilaria immitis or prevent recurrence of circulating microfilariae of B. malayi in ferrets infected with adult filariae.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 4029350 TI - Ascaris suum: role of ecdysteroids in molting. AB - Three studies were conducted to examine the function of ecdysteroids in the development of parasitic nematodes. Ecdysone and 20-hydroxyecdysone were extracted, separated chromatographically, and measured in the reproductive tracts of adult female Ascaris suum. Perienteric fluid and the body wall did not contain measurable levels of these steroids. Levels of 20-hydroxyecdysone were correlated with the third and fourth molts of larvae grown in vitro from the third stage. In a bioassay, addition of ecdysteroid extracted from the female reproductive tract or synthetic ecdysteroid increased the proportion of third-stage larvae that molted after 4 days in culture. This evidence supports the role of ecdysteroids in molting in A. suum, as well as suggesting a function in gametogenesis and embryogenesis. PMID- 4029351 TI - Nematoda: susceptibility of the egg to Bacillus thuringiensis toxins. AB - Crystalline toxins from Bacillus thuringiensis israelensis and B.t. kurstaki were lethal in vitro to eggs of the nematode Trichostrongylus colubriformis. The LD50 values for the two toxins were 0.38 ng and 37.5 micrograms total protein/ml, respectively. After 1 week at ambient temperature, the LD50 of B.t. kurstaki decreased to less than 4 micrograms/ml. Toxin from B.t. israelensis had no effect within 48 hr on survival of adult nematodes or on their feeding in vitro. Third stage larvae of T. colubriformis were also unaffected by B.t. israelensis toxin. Exposure of third-stage larvae of Nippostrongylus brasiliensis to 1.1 micrograms total protein/ml of B.t. israelensis for 4 hr had no effect on their infectivity in mice, based on recovery of helminths at 7 days after infection. Similar exposure of 5-day-old N. brasiliensis and subsequent transfer into the intestine of mice gave recoveries that were similar to the untreated control. Thirty strains of B. thuringiensis caused mortality in nematode eggs, but over a 77,000 fold range of activity was found, based on the LD50 values. Toxin from B.t. israelensis was lethal to eggs of six zooparasitic and one free-living species of nematode, but the LD50 values varied 28-fold. Addition of B.t. israelensis to feces that contained eggs of T. colubriformis reduced subsequent recovery of larvae, with an LD50 of 260 ng/g of feces. PMID- 4029353 TI - An ultrastructural study of the vascular alterations within the carotid bodies of spontaneously hypertensive rats (SHR). AB - Electron microscopic studies of the fine structural changes of the arterioles within the carotid bodies of spontaneously hypertensive rats (SHR) in the established phase of hypertension revealed partly hyperplastic endothelial cells. In the subendothelial space a multiplication of the basal laminae was observed often of a whirl-like shape. The smooth muscle cells of the media were hypertrophied, bizarre and with numerous projections. They exhibited a marked increase in cell organelles. The extracellular space was extensively enlarged and partly vacuolated. It contained a basement membrane-like material which was connected with the basal laminae of the myocytes. All these alterations produced a pad-like thickening of the arteriolar wall which narrowed the vessel lumen. These findings and their possible effects on carotid body function are discussed. PMID- 4029352 TI - Ascaris suum: protective immunity in pigs immunized with products from eggs and larvae. AB - Parasite products were collected at three distinct phases of development of Ascaris suum, and their immunogenicity was determined after injection into rabbits and pigs. Products were derived from (1) the hatching fluid of infective eggs; (2) the conditioned medium of 2nd-stage larvae that developed to 3rd stage in vitro in defined medium; and (3) the conditioned medium of 3rd-stage larvae that developed to 4th stage in vitro in defined medium. Protein profiles from these three preparations, separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, were less complex than that of extracts from homogenized A. suum larvae. Hyperimmune rabbit antiserum raised against either egg products, 2nd- to 3rd-stage larval excretory-secretory products, or 3rd- to 4th-stage larval excretory-secretory products showed strong homologous reactions after immunoelectrophoresis, but relatively weak cross-reactions with the other preparations. A combined enteral immunization of pigs with egg products and parenteral immunization with the 2nd- to 3rd-stage larval excretory-secretory products, and 3rd- to 4th-stage larval excretory-secretory products induced antibody to each preparation and significant protective immunity to a challenge exposure with 10,000 A. suum eggs. However, a marked pathological response to larvae migrating in the liver after challenge exposure was also induced. PMID- 4029354 TI - The influence of the pH value of the synovial fluid on the articular cartilage in rabbits. A scanning electron microscopic study. AB - After the intraarticular injection of isoosmolaric buffer solutions with pH values of 4.0 and 10.0 or 7.3 (control side) into the knee joints of rabbits the appearance of a fibrillated network on a plane parallel to the surface and tears in the articular cartilage are seen with the aid of scanning electron microscopy. The results are interpreted as a damage of the superficial layer of the articular cartilage. In a long-term follow up only the growing rabbits are able to repair these lesions, the adult animals are not capable to do it. PMID- 4029355 TI - Inducibility of the hepatic microsomal monooxygenase system experimentally reduced to a minimum amount/activity. Effect of hypophysectomy, partial hepatectomy and phenobarbital/toluene treatment on the hepatic polysubstrate monooxygenase system in rats. AB - Sham-operated, hypophysectomized, partially hepatectomized and hypophysectomized + partially hepatectomized groups of CFY rats were treated with phenobarbital (40 mg/kg/day) per os or physiological saline once a day, or toluene-vapour (inhalation: 4,000 mg/m3, 8 h/day), for 3 days. The polysubstrate monooxygenase (PSMO) system of the liver was induced by phenobarbital after all kinds of surgical interventions. Inducibility of the enzyme system was the highest in the group with combined hypophysectomy + partial hepatectomy and decreased in order in the groups with partial hepatectomy, hypophysectomy and sham-operation. The relative cytochrome P-450 content (quantity of cytochrome P-450/100 g b.w.) was the lowest after combined operation, higher in partially hepatectomized and hypophysectomized animals and it was the highest in the sham-operated group. Hypophysectomy after partial hepatectomy seems to inhibit hepatic regeneration and to increase the inducibility of the enzyme by phenobarbital, at the same time. Phenobarbital treatment brought about SER proliferation in a part of liver cells, in each group. In case of repeated liver damage due to the consequences of hypophysectomy, partial hepatectomy, phenobarbital administration, a group of the liver cells responds to the first, another to the second, but even after the third injury a group of the liver cells maintained its regular structure. The hypothetical hepatotoxic effect of toluene, a widely used industrial solvent, has been tested. Hepatotoxicity has been excluded. The minimum non-specific hepatotoxic effect of the solvent was not augmented by either partial hepatectomy or hypophysectomy, or by the combination of the two. In all the experimental groups toluene increased the hepatic cytochrome P-450 level and induced a moderate increase in SER. Inducibility of the enzyme system after toluene inhalation was similar to that of the enzyme system after phenobarbital treatment in each group. PMID- 4029357 TI - Studies on quantitative morphology. IX. Component distribution in the thyroid gland of a hamster. AB - Morphometric investigations were performed on equidistant stage sections of a hamster thyroid gland, which led to the following conclusions: In sections of the outer regions there are observed higher relative colloid percentages and lower data for the epithelium in relation to the values of sections of the middle part. Therefore the ratio epithelium: colloid is higher in the central region. There are high negative correlation coefficients for the comparison of these main constituents, but low values are calculated between the relative interstitium percentages and the epithelium: colloid ratio. Both of the lobes of the thyroid gland showed different volumes, but nearly the same composition. Up to a section distance of approximately 500 micron most of the relative colloid percentages of bodies, constructed by all requisite section areas and the corresponding section distances, are laying in a range of +/- 5% in relation to the value, which was calculated from all sections with a distance of always 20 micron. For the epithelium percentages such a borderline was found near 400 micron. A sharper criterion is the ratio epithelium: colloid. All data beneath a section distance of 200 micron are lying in a +/- 5% range, since +/- 10% borderlines are not exceeded up to 500 micron. This corresponds to about 5 sections per lobe in this example, which were measured in less than half an hour. PMID- 4029356 TI - Experimental arteriosclerosis and the plasma kininogen and low molecular weight kininogen antigen concentration in rabbits. AB - A decrease in trypsin-releasable kinin and in low molecular weight kininogen antigen concentrations was observed in plasma of rabbits with cholesterol-induced arteriosclerosis. In rabbits receiving normal diet for 30 days after 30 days of cholesterol almost complete normalization of the morphological status was observed, which was accompanied by normalization of plasma kinin concentration and by higher than normal concentration of kininogen antigen measured. These changes were not observed in animals receiving normal diet for 30 days after 60 days of cholesterol administration. No data were obtained suggesting a massive kinin release during induction of arteriosclerosis by experimental hypercholesteremia. The possibility of intense kinin formation during a period of repair of the morphological changes was discussed. PMID- 4029358 TI - Increased serum triacylglycerol and cholesterol binding reserve in acute uremic rats. AB - In acute uremic rats (24 h after bilateral nephrectomy, serum urea 280-300 mg/dl) the interface tension of the serum is significantly reduced. Serum levels of triacylglycerol are significantly elevated in uremia, whereas cholesterol levels do not show a significant alteration. The in vitro serum binding reserve for both, triacylglycerol and cholesterol is considerably enhanced. These results let suppose the presence of tenside-like substances in uremic serum which may be involved in disturbed triacylglycerol transport from the serum to the tissues and in development of uremic hypertriglyceridemia. PMID- 4029359 TI - The importance of the lymphatic system. PMID- 4029360 TI - Splenic infarcts produced in rats by vasoconstrictor drugs. AB - Investigation of the role of vasoconstriction in the production of infarcts would be facilitated by a model based on a non-essential and readily accessible organ. Therefore, we investigated the effects of intraperitoneal injections of vasoconstrictor drugs on spleen and liver in the rat. Phenylephrine produced infarcts of the spleen regularly and infarcts of the liver occasionally. Epinephrine was also effective in rats that had been pretreated with tilorone. The lesions were caused by local (topical) effects of the drugs. In support of this conclusion, reduced perfusion of the target areas was demonstrated in vasoconstrictor-treated rats given India ink intravenously. In addition, splenic infarcts were produced either by intraperitoneal injection or by direct application of epinephrine to the surgically exposed spleen. On the contrary, splenic infarcts were not produced by injections of epinephrine outside the peritoneal cavity, or by intraperitoneal injections if the spleen had been transposed outside of the cavity beforehand. Thus, we have produced an experimental model of splenic infarcts caused by topical application of vasoconstrictor drugs which is reminiscent of the speckled spleen (Fleckmilz) of human pathology. PMID- 4029361 TI - Mathematical models of cell variation seen in a heterogeneous malignant cell population. AB - We established mathematical models for the cell variation seen in a heterogeneous malignant cell population, with the supposition that it occurs as the result of the competition between two types of cells, (A) and (B), leading to a change of stem cells. Models I and II: In the case of differences in the ability of (A) and (B) cells to adapt themselves to an environment, the proportion of cells which are less adaptable to the environment decreases exponentially and eventually disappears. Model III supposes that under certain environmental conditions, the two types of cells exist simultaneously in fixed proportions, and transformations of (B) cell to (A) cell and of (A) cell to (B) cell occur at a certain rate but are independent of each other. This process is considered to follow the Markov's chain theory. Based on this supposition, we established Model III and introduced the concept of "coefficient of cell variation". We found that Model III fits the process of cell variation seen in m cell line and we calculated the coefficients of cell variation seen in this cell line in different environments. The possible mechanism of the cell variation of this cell line is discussed. PMID- 4029362 TI - Long-term inhalation study with benzo(a)pyrene and SO2 in Syrian golden hamsters. PMID- 4029363 TI - Ultrastructure of the epithelial cells of the small intestinal villi, the surface epithelium of the large intestinal mucosa and some elements of the intestinal mucosal lamina propria in rats with acute uraemia. AB - Electron microscopic studies on the dynamics of changes in the epithelial cells and some elements of the intestinal mucosal lamina propria were performed on rats after bilateral high ureter ligation. Simultaneously, they were referred to blood serum biochemical and electrolyte disturbances. The ultrastructural changes indicate that as early as in the initial period of acute uraemia water electrolyte disturbances become evident, which are still increasing. In the later period cell organelles alter and bacterial infection sets in. Ultrastructural abnormalities of the intestinal mucous membrane are increasing proportionally to biochemical and electrolyte disturbances of the blood serum. PMID- 4029364 TI - Functional impairment of mitochondria from rat livers acutely injured by thioacetamide. AB - Thioacetamide, when administered in a dose of 100 mg/kg body weight to adult female rats, leads to functional disturbances in mitochondria isolated from livers 24 h after its application. The RCI is significantly reduced due to an increase in state 4 respiration and a lowered state 3 activity. Maximum respiratory activity of the mitochondria is also depressed. The mitochondrial Ca2+-content is significantly increased to 185%. In accordance with the uncoupling effect the Ca2+-transport behaviour of the hepatic mitochondria from thioacetamide-injured rats is altered. The results are indicative of structural alterations of the inner mitochondrial membranes. PMID- 4029366 TI - Residues of veterinary drugs in foods. Report of a joint FAO/WHO expert consultation, Rome, 29 October-5 November 1984. PMID- 4029365 TI - Correlation between in vitro autoradiographic results and histological WHO grades in human urothelial bladder tumours. AB - 253 biopsy specimens of 106 urinary bladder tumours have been examined by means of in vitro autoradiography and the results compared with the WHO grading. An increase of the average labelling index occurred parallel to increasing WHO grades. However, great inter-tumorous differences in proliferation behaviour existed particularly in papillary G2 and G3 urothelium carcinomas. Possible causes of this heterogeneity are discussed. In vitro autoradiography is a suitable method for the objective characterization of the malignancy potential of urinary bladder tumours. PMID- 4029367 TI - [Simultaneous determination of oxprenolol and chlorthalidone in pharmaceutical preparations with derivative spectrophotometry]. PMID- 4029368 TI - Effective surface area and activity of antacid preparations. PMID- 4029369 TI - [Determination of catalytic constants of an acetic acid-sodium acetate buffer in comparison with amoxicillin trihydrate]. PMID- 4029370 TI - Toxicological aspects of a new tripeptide mustard. PMID- 4029371 TI - Drug permeation through directly compressed polymeric barriers. PMID- 4029372 TI - [Assay of 1,3-diiodo-2-propanol (Iothion) in various pharmaceutical preparations]. PMID- 4029373 TI - On the spectrophotometric analysis of phenolphthalein. PMID- 4029374 TI - [Effect of 7-hydroxygluacine on brain biogenic monoamines]. AB - In experiments on male albino rats it was established that the aporphine alkaloid 7-hydroxyglaucine injected i.p. at a dose of 1/10 of the LD50 induced many changes in the brain level of biogenic amines. Serotonin content was significantly increased in all brain structures studied (whole brain. cortex, striatum, and hypothalamus) Dopamine level was increased in the whole brain and cortex and was decreased in the hypothalamus; noradrenaline level was increased in the cortex and was decreased in the whole brain and hypothalamus. These effects are thought to be due to the 7-hydroxyglaucine-facilitated transport of amino acids, precursors of biogenic amines, and to neurotransmitter interactions in the different brain structures. PMID- 4029375 TI - [Characteristics of the action of non-narcotic analgesics in diabetics]. AB - Patients with diabetes mellitus were examined for the action of non-narcotic analgesics during oral cavity sanitation. All the drugs under study (amidopyrine, pyranal, baralgin, probon) taken per os increased the threshold of tactile painful sensitivity and the threshold of pain endurance in patients with diabetes mellitus to a greater degree than in normal subjects. No such differences were recorded after diazepam intake under the same conditions. PMID- 4029376 TI - [Pain-alleviating action of gidifen and its combinations with analgesics]. AB - The analgesic effect of gidifen, a new tranquilizer belonging to the group of organophosphorus compounds, manifests itself in relatively high doses (1/3 of the LD50). The quantitative characteristics of the analgesic action depends on the method for evaluating the analgesic action of the drug. On combined use of gidifen and analgesics applied in a definite dosage range the analgesic effect is potentiated. If the tranquilizer under study is combined with non-narcotic analgesics, the above potentiation is accompanied with an increase in the toxicity and myorelaxant activity of gidifen. On combination of the latter with morphine the parameters under consideration are unchanged. According to the pattern of interaction with analgesics gidifen does not differ in principle from benzodiazepine tranquilizers. However, the drug is not superior to benzodiazepines in this respect. PMID- 4029377 TI - [Evaluation of the pain-alleviating properties of a combination of analgesic and tranquilizer using multiple stepwise regression]. AB - A method for preclinical evaluation of the optimal ratio (for analgesia) of an analgesic to a tranquilizer has been devised. It is based on the drug threshold dose decrease on the drug combined use. The multiple stepwise regression analysis of the data discovered the correlations between diazepam and promedol, optimal for pain perception decrease and nociceptive emotional responsiveness inhibition. PMID- 4029378 TI - [Effect of nonachlazine on the temperature sensitivity of the lysosomal membranes of the heart muscle in rats in vitro]. AB - It has been shown in vitro that nonachlazine stabilizes rat myocardial lysosomal membranes and activates total acid phosphatase in homogenates of rat myocardium. Preliminary addition of nonachlazine to homogenates in two different final concentrations produces unequal changes in total and free activity of acid phosphatase and cathepsin D during 2.5-hour incubation of homogenates at 37 degrees C. PMID- 4029379 TI - [Effect of adrenaline and acetylcholine on the phosphatidylserine decarboxylase activity of the heart]. AB - The authors have established the presence of phosphatidylserine decarboxylase in the sarcolemma. The capacity of this enzyme to change under the influence of adrenaline and acetylcholine has been brought to light. PMID- 4029380 TI - [Antifibrillatory activity of anti-arrhythmia agents in maximally high ligation of the coronary artery and its reperfusion in cats]. AB - Experiments on anesthesized cats were performed to study antifibrillatory action of the basic antiarrhythmic remedies and a new Soviet drug, phenicaberan. It was established that phenicaberan and lidocaine compare very favourably with other drugs under study as regards the antifibrillatory effect. For that reason these drugs can be recommended for use in the prophylaxis of fatal arrhythmias. PMID- 4029381 TI - [Effect of unithiol on the ultrastructure of the myocardium and adrenals in endotoxin shock]. AB - Administration of unithiol to animals with endotoxin shock promotes deposition of catecholamines in chromaffin cells of the adrenals, blocks their secretion to the bloodstream and prevents the development of injuries to the cortical substance of the gland. Administration of unithiol for endotoxemia prevents damage to intracellular organelles of cardiomyocytes. However, insignificant disorders of the contractile apparatus of the cells and histohematic barriers are maintained. The capacity of unithiol to prevent the progress of destructive alterations in the heart and adrenals permits recommending it for use in combined treatment of septic conditions. PMID- 4029382 TI - [Effect of a fatty-series narcotic (ether) and a barbiturate (hexenal) on the regional distribution of the total and nutritive blood flow]. AB - Inhalation of diethyl ether and intraperitoneal injection of hexenal in doses that provide a surgical state of anesthesia are accompanied by changes in the regional tone of the resistive blood vessels as well as by those in the ratio between the nutritive and shunting fractions of the blood flow in organs and tissues. The increase in the rate and enlargement of the area of transcapillary metabolism in the brain and myocardium (notwithstanding the decrease of the total blood flow in these organs) by means of the increased shunting fractions of the blood flow in vast skin and skeletal muscle areas are considered to be the most important events. Diethyl ether and hexenal cause different changes in the hepatic and renal hemodynamics. PMID- 4029383 TI - [Effect of prednisolone, hyperbaric oxygenation and their combination on the glucose content of the blood and glycogen in the organs of white rats]. AB - A single injection of prednisolone in doses of 10, 30, 80 and 100 mg/kg provoked different shifts in blood glucose concentration and glycogen content in the heart, liver, and skeletal muscles. Prednisolone increased liver glycogen content almost in all the doses. Administered in doses of 10 and 30 mg/kg the drug reduced blood glucose level and glycogen content in the myocardium and skeletal muscles. Administered in doses of 80 and 100 mg/kg the drug produced almost no effect on the characteristics under consideration or increased them. Oxygen raised glycogen liver content, blood glucose level, reduced the content of the polysaccharide in the skeletal muscles at a pressure of 3039 Pa (3 at. abs). Combined use of prednisolone and oxygen at an elevated pressure led, depending on the drug dose, to the occurrence of the phenomena of either synergism or antagonism. PMID- 4029384 TI - [Prognosis of the effectiveness of hypotensive therapy]. AB - Based on the data obtained in acute clinico-pharmacological tests with 0.075 mg hemiton, 250 mg dopegyt and 40 mg anaprilin in patients with stage II essential hypertension a system of predicting the efficacy of hypotensive therapy has been designed. It has been established that the hypotensive effects of the indicated drugs can be predicted with the aid of the system not only under the conditions of acute clinico-pharmacological tests but also during treatment given in courses. PMID- 4029385 TI - [Effect of courses of acetylsalicylic acid and sodium salicylate administration on the carbohydrate-phosphorus metabolic indices in vascular tissue]. AB - Experiments on 78 adult rats were made to study the effects of acetylsalicylic acid and sodium salicylate administered daily for 7 and 14 days on the content of pyruvic, lactic, citric acids and inorganic phosphate in the wall of blood vessels of different function. Salicylates were demonstrated to reduce the content of citric acid by the 7th day and that of pyruvic acid by the 14th day, to increase the level of lactate and inorganic phosphorus during both observation periods. The degree of the changes revealed is unequal in different vessels, being more pronounced after sodium salicylate administration. PMID- 4029386 TI - [Effect of teturam in the alcoholic intoxication of male rats on the biogenic amine level of the brain of progeny]. AB - It has been established in experiments on rats that the action of teturam and alcohol on brain biogenic amine metabolism is mediated by males. It has been shown that in animals with alcoholic intoxication, teturam does not potentiate the effect of alcohol on the content of biogenic amines. PMID- 4029387 TI - [Effect of alcohol on the 11-hydroxycorticosteroid and 17-ketogenic steroid levels in man taking into account biorhythms]. AB - Circadian rhythms of 11-hydroxycorticosteroids (11-OHCS) in blood plasma and 17 ketogenic steroids (17-KGS) in urine in health and for 3 days after a single intake of 40 per cent alcohol (6.2 ml/kg) from 17.00 to 18.00 were studied in 20 healthy men volunteers aged 20 to 26 years. Alcohol considerably raised the level of 11-OHCS and 17-KGS during its circulation in the blood. After ethanol elimination was completed, there was a decrease in the level of corticosteroids, which was observed even on the 2nd day after alcoholization during rhythm acrophases. Alcoholization resulted in variations of the mesors, amplitudes and acrophases of circadian rhythms throughout two days. The recovery of normal time structure occurred on the 3d day. PMID- 4029388 TI - [New psychotropic agents. I. Synthesis and pharmacologic activity of derivatives of 5H-imidazo-[2,1-c][1,4]benzodiazepine]. AB - The synthesis of 5H-imidazo [2,1-c] [1,4] benzodiazepine derivatives is described. Hydroxymethylation of 1-(2-nitrobenzyl)imidazoles by reaction with formaldehyde in a sealed tube and subsequent oxidation of hydroxymethylimidazoles with activated manganese dioxide afforded 1-(2-nitrobenzyl)imidazole-2 carboxaldehydes. The latter compounds were treated with iron(II) sulphate to yield directly the expected tricyclic imidazobenzodiazepines by intramolecular cyclization of the intermediates aminoaldehydes. The tricyclic derivatives were subjected to pharmacological screening to evaluate the effects on the behavior of the animals and the interaction with some biogenic amines. Some of the tested compounds were comparable to chlordiazepoxide in sedative and muscle-relaxant activities. None of them showed antiserotonin, anticholinergic or adrenolytic activities. PMID- 4029389 TI - Modification of the skeletal muscle energy metabolism induced by intermittent normobaric hypoxia and treatment with biological pyrimidines. AB - Muscular glycolytic fuels, intermediates and end-products (glycogen, glucose, glucose-6-phosphate, pyruvate, lactate), Krebs cycle intermediates (citrate, alpha-ketoglutarate, succinate, malate), related free amino acids (glutamate, alanine), ammonia, energy store (creatine phosphate), energy mediators (ATP, ADP, AMP) and energy charge potential were evaluated. Furthermore the maximum rate (Vmax) of the following enzyme activities was evaluated in the crude extract and/or mitochondrial fraction: for the anaerobic glycolytic pathway: hexokinase, phosphofructokinase, pyruvate kinase, lactate dehydrogenase; for the tricarboxylic acid cycle: citrate synthase, malate dehydrogenase; for the electron transfer chain: total NADH cytochrome c reductase, cytochrome oxidase. The rat gastrocnemius muscles were analysed in normoxia and after normobaric intermittent hypoxia (12 hours continuously daily; for 5 days). Cytidine and/or uridine were administered daily at the dose of 120 mg/kg, i.p., 30 min before the beginning of the experimental hypoxia. The intermittent normobaric hypoxia induced a biochemical adaptation characterized by the decrease of the muscular contents of creatine phosphate, citrate, alpha-ketoglutarate and glutamate. This adaptation occurred in the absence of significant changes in the Vmax of the tested muscle enzymes. In gastrocnemius muscle from hypoxic rats, the two biological pyrimidines tested induced various discrete, but often related, modifications of the contents of some Krebs cycle intermediates (i.e., alpha ketoglutarate, malate) and related free amino acids (i.e., glutamate, alanine). In any case, the treatment with cytidine and/or uridine did not modify the Vmax of marker enzymes related to energy transduction. PMID- 4029390 TI - Opioid peptides. VIII. Synthesis and preliminary biological activity of [D-Phe3]- or [alpha,beta-dehydro-Phe3]dermorphin tetrapeptides. AB - We describe the synthesis and preliminary in vitro pharmacological testing of two new tetrapeptide analogues of the opioid heptapeptide dermorphin H-Tyr-D-Ala-Phe Gly-Tyr-Pro-Ser-NH2. The replacement of Phe3 by its D-enantiomer was hardly if at all tolerated. The unsaturated analogue carrying the phenyl ring of the delta Phe3 residue in the Z-configuration, was almost inactive. PMID- 4029391 TI - Deoxythymidine pools of human skin and guinea pig organs. AB - The activity of antiviral nucleoside analogues like acyclovir is influenced by a number of cellular factors, one being the deoxythymidine (dThd) concentration. We therefore analysed the dThd concentration in human plasma and skin and in organs of guinea pig, the common experimental animal. High-performance liquid chromatography showed low amounts of dThd in human skin, 0.20-1.15 nmol/g, whereas guinea pig skin and spleen had 20-30 nmol/g and the concentration in guinea pig plasma was 10-times higher than in human plasma. These animals are therefore in this respect less suitable as accurate models for antiviral nucleoside activity in humans. PMID- 4029392 TI - Electrochemical detection of biogenic amines following acylation by N hydroxysuccinimide esters. AB - A general methodology for the selective derivatization of amines, to enable quantitation by high pressure liquid chromatography with electrochemical detection, is presented. N-Hydroxysuccinimide active esters present in large excess are suitably mild acylating agents to derivatize selectively trace quantities of amines for electrochemical detection. The 2 separate problems of extraction yield and detectability can be solved by this derivatization method. Due to its lipophilicity the resulting N-acylated amine, as demonstrated with serotonin, is extracted efficiently into organic solvents during sample preparation for chromatography. Moreover, the acyl group introduced can be designed to be electroactive, thus extending the procedure to amines not readily oxidized, e.g., histamine and phenylethylamine. PMID- 4029393 TI - Increased mitochondrial creatine kinase in chronically stimulated fast-twitch rabbit muscle. AB - Fractional extraction and isozyme electrophoresis revealed the presence of small amounts (2.5% of total cellular activity) of mitochondrial creatine kinase (CK) in rabbit fast-twitch muscle. Chronic nerve stimulation resulted in a decrease of extramitochondrial MM-CK to 60% of its normal value but induced an approx. 4-fold increase in mitochondrial CK. This increase occurred in parallel with the rise in enzyme activities of terminal substrate oxidation. PMID- 4029394 TI - Biochemical evidence that acetylcholine release from cholinergic nerve terminals is mostly vesicular. AB - The nature of the intraterminal compartments from which acetylcholine (ACh) is released following presynaptic stimulation was investigated. This was pursued by examining the effects of the anticholinergic drug 2-(4 phenylpiperidino)cyclohexanol (AH5183) on the release of newly synthesized [3H]ACh and of endogenous ACh from purified cholinergic nerve terminals (synaptosomes) which were isolated from the electric organs of Torpedo. Preincubation of the synaptosomes, with AH5183 (1-10 microM), does not affect either the intraterminal synthesis of [3H]ACh or the uptake of its precursors, but results in a marked inhibition (85%) of the release of the newly synthesized [3H]ACh. However, when AH5183 is added following the accumulation of [3H]ACh in the nerve terminals, it does not affect [3H]ACh release. AH5183 also has no effect on the release of preformed endogenous ACh. These findings, together with the previous in vitro demonstrations that AH5183 is a potent inhibitor of ACh uptake into isolated cholinergic vesicles, suggest that most of the synaptosomal ACh is secreted by a vesicular mechanism. PMID- 4029395 TI - Evidence of hemin as an end product inhibitor of L-alanine: 4,5-dioxovalerate transaminase in rat liver mitochondria. AB - This study describes the in vitro and in vivo effect of hemin on L-alanine:4,5 dioxovalerate transaminase activity. Hemin was shown to be an inhibitor of the purified enzyme and this inhibition was proportional to the concentration of hemin. The examined kinetic data with hemin showed uncompetitive inhibition for both alanine and 4,5-dioxovalerate. An apparent Ki of 30 and 42 microM for hemin were obtained with both alanine and 4,5-dioxovalerate, respectively. Moreover, the enzyme activity in liver was considerably decreased after the intravenous hemin administration and such an inhibition is dose and time dependent. Furthermore, maximum inhibition of the enzyme was observed 30 min after hemin injection and 60% enzyme inhibition was achieved with a dose of 1.2 mg/kg body wt of rat. Thus is suggests the important role of this enzyme on heme biosynthesis. PMID- 4029396 TI - Site specificity of iron removal from transferrin by alpha-ketohydroxypyridine chelators. AB - The site specificity of the removal of iron from diferric human transferrin, at pH 7.4, by two alpha-ketohydroxypyridine chelators, 1,2-dimethyl-3-hydroxypyrid-4 one (L1) and mimosine, has been investigated using urea-polyacrylamide gel electrophoresis. Chelator L1 removes iron preferentially from the C-terminal site whereas mimosine shows a small preference for iron in the N-terminal site. The removal of iron has also been followed spectrophotometrically and by monitoring the loss of 59Fe from [59Fe]transferrin. Both chelators are able to remove iron completely from diferric transferrin without additional mediators or reducing agents. PMID- 4029397 TI - A monoclonal antibody reacting specifically with ganglioside GD1b in human brain. AB - A mouse monoclonal antibody directed against one of the major human brain gangliosides, GD1b, has been produced. The antibody binds specifically to the carbohydrate structure of GD1b as it does not react with structurally related gangliosides like GM1, GD2, GT1b or Fuc-GM1, or any other ganglioside of human brain. The results further indicate that terminal galactose as well as the disialosyl group linked to the inner galactose moiety are involved in binding to the antibody. PMID- 4029398 TI - Isolation and chemical characterization of glicentin C-terminal hexapeptide in porcine pancreas. AB - Using a radioimmunoassay specific for porcine glicentin C-terminal hexapeptide, we isolated a peptide from porcine pancreas and characterized it as the C terminal 64-69 sequence of glicentin: H-Asn-Lys-Asn-Asn-Ile-Ala-OH. The purification steps included gel filtration, ion-exchange chromatography and HPLC. In each step, the recovery of the desired peptide, radioimmunologically estimated from the respective elution profile, was 71.4-91.7%. The final yield of the hexapeptide was 22 micrograms (4.3%) from 800 g pancreas. The pancreatic content of this peptide was estimated to be approximately equimolar to that of pancreatic glucagon. No hexapeptide-like component was detected in porcine intestinal extracts. The data confirmed that the processing of pancreatic proglucagon liberates the C-terminal hexapeptide of the intramolecular glicentin sequence in a tissue-specific manner during the production of glucagon. PMID- 4029399 TI - Use of phosphorothioate analogs of poly(dA-dT).poly(dAdT) to study steroidal diamine induced conformational change in poly(dA-dT).poly(dA-dT). AB - Introduction of phosphorothioate groups into the backbone of poly(dA-dT) allows one to label the d(ApT) and d(TpA) phosphate resonances in the 31P NMR spectrum. Upon binding the steroidal diamine dipyrandenium to poly d(AsT) and poly d(TsA), 31P NMR shows that it is the d(ApT) phosphodiester bond which is most perturbed. Other work has shown that 2 M Cs+ causes the same 31P shift. The DNA conformational change induced by both cations probably involves a narrowing of the minor groove. PMID- 4029401 TI - Abdominal staging surgery. PMID- 4029400 TI - Sequence homologies among mitochondrial DNA-coded URF2, URF4 and URF5. AB - Amino acid sequences coded for by 13 different genes of mammalian mitochondrial DNA (mtDNA) including 8 unassigned open reading frames (URFs) were compared in pairs. It was found that significant homologies exist among the amino acid sequences of the three URFs (URF2, URF4 and URF5) with a probability of occurrence of less than 10(-5). This result strongly suggests that the 3 URFs evolved from a single ancestral gene by a series of gene duplications. A phylogenetic tree based on the alignment of the URF sequences from mammals, an insect, a fungus and protozoa revealed a very remote divergence of the 3 URFs, going back to a time before separations of animal/protozoa and animal/fungus. PMID- 4029402 TI - The health of rectal cancer patients in the community. AB - Surviving rectal cancer patients living in five health districts were identified through cancer registrations. Four hundred and twenty (91%) were interviewed at home by health visitors to assess their physical, social and psychological health. In most respects, the health of rectal cancer patients overall was similar to that of the general population of the same age, sex and social circumstances. However, those with a colostomy (63%) were more likely to be severely depressed, socially isolated and stigmatized. They also suffered more from physical problems, particularly urinary symptoms, flatus and offensive bowel motions. The pressure of a colostomy was associated with reduced sexual capacity, though not with lack of sexual interest. The results confirm the high psychological and social costs of a permanent colostomy. PMID- 4029403 TI - Study of the histochemical changes in mucus from normal and tumour bearing mucosa in patients with colorectal cancer. AB - The prognosis in colorectal cancer is related to the stage of the tumour. Thus, early detection of developing tumours will significantly improve the overall prognosis. This study assessed the histochemical changes in mucus from normal and tumour bearing mucosa to determine possible premalignant changes. Eighty patients with colorectal cancer and ten normal subjects were studied. Biopsies were taken from the tumour and from adjacent 'normal' mucosa and from both resection edges. Sections were stained with high iron diamine-alcian blue to distinguish sulphated from sialomucins. All normal mucosal biopsies showed a predominantly sulphated mucin pattern. By contrast, all 70 tumour mucosal biopsies showed a marked sialomucin staining. In transitional mucosa adjacent to the tumour, 30 patients showed marked increase in sialomucin (2+), 42 a moderate increase (+) and the remaining eight a normal pattern (-ve). Twenty-one (15%) patients had increased sialomucin at either surgical resection margins, all of whom had similar changes adjacent to the tumour, suggesting a wide field change in the mucus pattern. Since these changes in mucus are associated with malignant transformation then estimation of mucus pattern may give early prediction of malignant change in patients at risk of developing primary or recurrent carcinoma. PMID- 4029404 TI - The functional results following primary treatment of breast cancer with breast conservation. AB - Forty-seven patients who had local excision ('lumpectomy') and radical radiotherapy for carcinoma of the breast in 1982 were assessed at 1 year for the functional result. The appearance of both breast was identical in 34%, while in 10% serious distortion had occurred. No matchline effect or severe telangiectasia were seen, and no patient had arm oedema, restricted arm movements or severe pain. The results were not significantly better (1) following iridium implantation than external boost, (2) after periareolar rather than other incisions, and (3) in patients with small and medium rather than large breasts. PMID- 4029405 TI - Deoxyribonucleic acid (DNA) content of primary carcinoma and response to endocrine or cytotoxic drug therapies in patients with advanced breast cancer. AB - The DNA content of primary carcinomas was estimated colorimetrically in 111 patients with carcinoma of the breast who subsequently developed metastatic disease. The data were analysed to investigate whether these measurements will assist clinicians in predicting: survival from mastectomy or recurrence, the likelihood of response to the first endocrine or the first cytotoxic drug therapy, duration of response amongst responders to these treatments, and time to treatment failure (TTTF). The DNA content of primary carcinomas failed to predict the clinical course of the disease for patients who underwent endocrine treatments. In patients who were treated by cytotoxic drug therapies, only the duration of response amongst responders to these therapies was significantly shorter in cases where the DNA content was high. The DNA content of carcinomas failed to give any useful information on other parameters. It is concluded that these measurements are unlikely to be of prognostic value in these cases. PMID- 4029406 TI - The treatment of early (T1) glottic and supra-glottic carcinoma: does partial laryngectomy have a place? AB - A series of 900 patients with laryngeal carcinoma is described. Patients with glottic T1N0 tumours were treated by radiotherapy with a 5-year survival of 92%. Seven per cent of patients suffered recurrence and most were salvaged by surgery: vertical hemilaryngectomy was occasionally useful as a salvage procedure. Patients with supra-glottic T1N0 tumours were treated for the first 7 years by supra-glottic laryngectomy and prophylactic neck dissection and thereafter by radiotherapy. The results were equally good in both series: a 5-year survival of 75-80%. Salvage surgery for failed radiotherapy or surgery for supra-glottic carcinoma gave poor results. PMID- 4029407 TI - Allopurinol mouthwashes and 5-fluorouracil induced oral toxicity. AB - Allopurinol has been shown to decrease the gastro-intestinal and bone marrow toxicity of 5-fluorouracil. In an attempt to diminish mucositis resulting from 5 fluorouracil administration, whilst not affecting its systemic anti-tumour activity, an allopurinol mouthwash has been used. In six patients who experienced mucositis when treated initially with 5-fluorouracil, the use of an allopurinol mouthwash with subsequent courses resulted in a reduction of oral toxicity. PMID- 4029408 TI - The choroid--an unusual site for metastasis in patients with adenocarcinoma of the rectum--a case report. AB - Metastatic carcinoma is the commonest malignant tumour of the eye and usually presents with a disturbance of vision. A rare case of choroidal metastasis secondary to adenocarcinoma of the rectum is reported to emphasize the need to investigate visual symptoms in patients with known or suspected malignant disease. PMID- 4029409 TI - Mesothelioma--short latent period after industrial asbestos exposure and prolonged survival. PMID- 4029410 TI - Breast lobular carcinoma in a fibroadenoma. AB - Lobular carcinoma arising in a fibroadenoma is a rare occurrence. A case is reported and literature is reviewed. Carcinomas developing in fibroadenomas are not intrinsically different from those not related to fibroadenomas. Prognosis and treatment are the same as for carcinomas of the same type arising outside and independently of fibroadenomas. PMID- 4029412 TI - Computer memories and word processors. PMID- 4029411 TI - Metastatic oligodendroglioma presenting as a leukoerythroblastic anaemia. AB - The clinical course of a patient with oligodendroglioma, treated initially with surgery and radiotherapy, is described. The patient later presented with leukoerythroblastic anaemia due to metastasis to bone marrow. This behaviour had not been previously described in oligodendroglioma. PMID- 4029413 TI - Vascular access for intravenous chemotherapy: totally implanted systems. AB - This is a prospective study conducted in order to evaluate totally implanted venous access systems. The report concerning 42 patients is presented. The follow up is 5 to 17 months (median 9 months). A variety of antineoplastic agents were administered through the device. Complications rarely occur and after utilization all patients are still treated in this way. Physician-, nurse- and patient acceptance were excellent and this system appears to improve the quality of life style of cancer patients. PMID- 4029414 TI - The use of sulphur hyperthermia in cancer. PMID- 4029415 TI - President Reagan signs bill requiring "no fewer than" 6,200 new NIH grants in FY 85. PMID- 4029416 TI - Quinacrine nonsurgical female sterilization: a reassessment of safety and efficacy. PMID- 4029418 TI - Isthmic ectopic pregnancy: segmental resection as the treatment of choice. AB - We reviewed the records of 12 patients who were admitted to Yale-New Haven Hospital between February 1979 and January 1983 with the diagnosis of isthmic ectopic pregnancy. All pregnancies were unruptured. Two patients were managed by salpingectomy. Ten patients were treated conservatively. Of the women managed by conservative surgery, four had a linear salpingostomy and none of the four conceived. Three of these four patients demonstrated occlusion of the operated tube by hysterosalpingogram (HSG). The other six patients were managed by segmental resection and delayed microsurgical anastomosis. Four of the six patients conceived. Three pregnancies were intrauterine and one was an ectopic pregnancy in the conserved tube. Three patients conceived before an HSG could be done. The remaining three patients had HSGs 3 to 4 months after anastomosis, and the operated tube was patent in all three. From these data and a review of the literature, we conclude that segmental resection with either immediate or delayed anastomosis appears preferable to linear salpingostomy for the conservative management of unruptured isthmic ectopic pregnancy. PMID- 4029417 TI - Four-year follow-up of insertion of quinacrine hydrochloride pellets as a means of nonsurgical female sterilization. AB - Eighty-four women were admitted to a study in Baroda, India, designed for evaluation of the efficacy of three transcervical insertions of quinacrine hydrochloride pellets, each 1 month apart, in producing occlusion of the oviducts. A 4-year follow-up has been completed for 100% of the women. Three women became pregnant during the time between the first and third administrations. Of the 81 women remaining in the study after administrations were complete, 3 became pregnant during the 4-year follow-up period, which resulted in a cumulative life-table pregnancy rate of 3.7 at 48 months. The results of this study indicate that intrauterine insertion of quinacrine pellets can be a safe, effective nonsurgical sterilization procedure. PMID- 4029419 TI - Ectopic pregnancy and antibodies to Chlamydia trachomatis. AB - Ectopic pregnancy is one of the most serious sequelae to acute salpingitis. Chlamydia trachomatis seems to be the most common etiologic agent of acute salpingitis. In the present study, we tested whether women with ectopic pregnancy had serologic evidence of a current or past chlamydial infection. Sixty-five percent of the women with ectopic pregnancy had IgG serum antibodies to C. trachomatis, and 21% of women pregnant in utero had such antibodies. Eleven percent of women with infertile husbands, 42% of women with cervicitis, and 69% of women with salpingitis had IgG serum antibodies to C. trachomatis. In women with ectopic pregnancy, there was a correlation between the occurrence of IgG antibodies and a history of salpingitis or gross evidence of a previous tubal inflammation. We conclude that previous chlamydial salpingitis may be a major etiologic factor leading to ectopic pregnancy. PMID- 4029420 TI - Embryo transfer technique as a cause of ectopic pregnancies in in vitro fertilization. AB - Against an overall risk of around 2% ectopic pregnancies in in vitro fertilization programs around the world, we report an incidence more than three times greater (5 tubal ectopic pregnancies in 80 clinical in vitro fertilization pregnancies). Of two techniques used for embryo transfers, one produced a significantly higher risk for ectopic pregnancy (P less than 0.05). Four of the ectopic pregnancies occurred in a small group of 24 patients in whom the embryo transfer technique attempted to deliver the embryos at the uterine fundus (mean distance of catheter insertion 62.9 +/- 7.9 mm from the external cervical os). Only one ectopic pregnancy occurred in 56 patients whose embryos were transferred to a standard, generally midcavity position. It is concluded that the delivery catheter need be inserted only 55 mm as a routine and less in patients with a shortened cervix or with the hypoplastic uterus usually encountered in women with primary ovarian failure who have ovum or embryo donation. In such cases an ultrasonic measurement of length may indicate that a shorter transfer distance is required. PMID- 4029421 TI - Estradiol in saliva for monitoring follicular stimulation in an in vitro fertilization program. AB - A rapid and sensitive radioimmunoassay (RIA) was developed to compare serum and saliva estradiol (E2) levels in patients undergoing ovulation induction in an in vitro fertilization and embryo transfer (IVF-ET) program. Serum and saliva E2 were compared in 23 patients. The sensitivity of the saliva RIA standard curve was 11 fmol/tube (equal to 3.2 pg/tube). There was a highly significant correlation between serum and saliva E2 throughout the stimulated cycles (r = 0.769; P less than 0.001). The ratio of serum to saliva E2 was constant throughout the stimulated cycles (1.7% +/- 0.3%, mean +/- standard deviation [SD]). The E2 concentration per follicle was 1548 pmol/l in serum and 23 pmol/l in saliva. Mean E2 levels in saliva (+/- SD) were 74 +/- 21 pmol/l at midcycle and 46 +/- 12 pmol/l at midluteal phase. The findings indicate that measurement of saliva E2 provides a reliable, noninvasive method and may replace serum measurements for monitoring stimulated cycles in an IVF-ET program. PMID- 4029422 TI - Analysis of the outcome of in vitro fertilization in relation to the timing of human chorionic gonadotropin administration by the duration of estradiol rise in stimulated cycles. AB - A retrospective analysis was carried out to assess the outcome of ovarian stimulation on in vitro fertilization when human chorionic gonadotropin (hCG) was administered after 5, 6, or 7 days of continuously rising plasma estradiol (E2). There was no significant difference in the number and size of large follicles in each group although the number of small follicles (less than 15 mm in diameter) decreased significantly after 7 days of E2 rise. After hCG injection in the 7-day group, the E2 level fell below the previous day's value in 40% of patients, whereas a similar fall was observed in only 16% of patients in the 5- and 6-day groups. In those cycles where a luteinizing hormone surge occurred, most surges were detected during the seventh day of E2 rise. The pregnancy rate was 31% when hCG was given after 6 days of rising E2, 21% after 5 days, and 14% after 7 days. In patients achieving pregnancy in the 6-day group, 53% of embryos were derived from leading follicles. In the 7-day group, only 15% of embryos associated with pregnancies were derived from leading follicles. These results strongly suggest that in stimulated cycles, hCG should be administered after 6 days of continuously rising E2. It is therefore postulated that 6 days of rising E2 represents a mean optimal period for follicular growth and oocyte maturation in stimulated cycles. PMID- 4029423 TI - Treatment of idiopathic infertility, cervical mucus hostility, and male infertility: artificial insemination with husband's semen or in vitro fertilization? AB - Couples with male infertility (n = 86), idiopathic infertility (n = 68), and cervical mucus hostility (n = 48) of a long duration were treated either by in vitro fertilization (IVF) or artificial insemination with husband's semen (AIH). The incidence of pregnancy per cycle in couples in whom the male partner was infertile was significantly (P less than 0.01) higher after IVF, compared with AIH (21% versus 5%, respectively). The differences were most apparent in couples with asthenospermia (47% versus 0%, respectively); no significant difference was found when the infertility was caused by oligospermia only (11% versus 9%, respectively). More patients with idiopathic infertility became pregnant after one cycle with IVF, compared with AIH (20% versus 8%, respectively); but, because of intragroup disparity in size, this difference was not significant. A highly significant difference (P less than 0.01) was found after one attempt with IVF, compared with AIH, in patients with cervical mucus hostility (38% versus 3%, respectively). PMID- 4029424 TI - Variances in mucus architecture as a cause of cervical factor infertility. AB - A cervical factor accounts for 5% to 10% of infertility among women. In the absence of an immunologic or endocrine-related basis for incompetent sperm/mucus interaction, an idiopathic cause is usually ascribed. This study describes quantitative analyses of the microstructure of mucin strands, observed under scanning electron microscopy, from infertile women displaying incompetent sperm/mucus interaction unrelated to any apparent immunologic or endocrine associated cause. The results revealed a highly significant reduction in the spacing of mucin fibers incompatible to sperm penetrability and migration. Additional quantitative measurements of mucin strand diameter and number and geometry of strand crosslinks suggest inadequate hydration of the mucin gel as a causative basis for the structural inadequacies observed in some cases of cervical-factor infertility. PMID- 4029425 TI - Measuring early pregnancy loss: laboratory and field methods. AB - We intensively studied 30 women attempting pregnancy in order to lay groundwork for larger studies of early pregnancy loss. These women collected first morning urine specimens for up to 6 months after discontinuing use of birth control. Urine specimens were successfully collected for 98% of the woman-days in the study. Three assays for human chorionic gonadotropin (hCG) were performed on each urine specimen. An immunoradiometric assay (IRMA) specific to the carboxyterminal peptide of the hCG beta-chain proved to be more sensitive and more specific than two radioimmunoassays (RIAs). Using the IRMA, we found four cases in which hCG rose and fell over successive days, consistent with early pregnancy loss. For three of these four cases, the level of hCG was too low to be detectable with the RIAs. Among the control group of five women with tubal ligations, there was no detectable hCG above threshold with the IRMA. Thus, the enhanced sensitivity and specificity of the IRMA allows very early pregnancy losses to be identified that would otherwise be undetectable. Furthermore, its effectiveness with small quantities of first morning urine makes the IRMA a useful tool for epidemiologic studies. PMID- 4029426 TI - Male factor evaluation in in vitro fertilization: Norfolk experience. AB - Thirty-three patients from the in vitro fertilization (IVF) program at Norfolk are critically reviewed. A battery of tests was designed and an endocrine investigation was carried out on these patients. The fertilization rate for preovulatory oocytes was lower than in the normal male population (39.6% versus 88.6%). When total concentration of sperm with rapidly progressive motility was less than 6 X 10(5), to fertilize several eggs together the fertilization rate was zero. No fertilization was obtained when the number of sperm with rapidly progressive motility recovered after the separation was less than 1.5 X 10(6). The hamster zona-free oocyte penetration test correlated well with the human IVF system. The other parameters investigated did not show good correlation. When fertilization was achieved, the results of the IVF procedure in the series reviewed rendered a 30.8% pregnancy rate per transfer in 26 transfers. Fifty percent of the pregnancies were normal (either ongoing or delivered). Thirty seven percent were preclinical miscarriages, and 12.5% were clinical abortions. In the abnormal male population, higher concentrations of sperm per egg should be used for insemination for achievement of optimum fertilization rates. Once fertilization is obtained, the results do not differ substantially from the IVF population at large. PMID- 4029428 TI - Variation of semen measures within normal men. AB - Variation in semen measures was assessed bimonthly in 15 healthy men over a 6 month period. Average within-subject coefficients of variation for sperm count, morphologic features, motility, and semen volume demonstrate considerable variation. Each day of abstinence increased the volume by an increment of 0.62 ml, the count by 17.6 X 10(6)/ml, and motility by 1.2%. Sperm count and semen volume correlated positively within subjects. Intraclass and serial correlations of semen measures provided an empirical clinical guide to the number and spacing of specimens. Three specimens spaced no more than 2 weeks apart established a reliable semen profile. Findings can be applied to basic research and clinical practice. PMID- 4029427 TI - Correlation between the direct IgG MAR test (mixed antiglobulin reaction test) and seminal analysis in men from infertile couples. AB - The direct IgG mixed antiglobulin reaction (IgG MAR) test was carried out in 395 male subjects from infertile couples, selected on the basis of their seminal characteristics (sperm concentration greater than 10 X 10(6)/ml, sperm motility greater than 10%); attempts were made to correlate results with the seminologic aspects of the ejaculate. A significant correlation was observed between a positive MAR test and spontaneous sperm autogglutination. No correlation was observed, however, between test positivity and concentration, motility and sperm morphologic features, the macroscopic aspects studied (viscosity, fluidification), or increased concentration of leukocytes. PMID- 4029429 TI - Properties of human epididymal sperm obtained from an alloplastic spermatocele: motility assessment and penetration of zona-free hamster oocytes in the presence and absence of caffeine. AB - Sperm were collected over a period of months from a human alloplastic spermatocele implanted at the corpus/caudal epididymal junction and were evaluated for their maturity, motility, and ability to capacitate and acrosome react, as assessed by the hamster zona-free oocyte sperm penetration assay (SPA). A mean of 11 X 10(6) sperm were obtained with each aspiration, with 34% to 40% being mature, normal forms. Motility was poor; 15% +/- 5% showing nonprogressive movement. SPA results were 22% +/- 3% oocyte penetration. Addition of 7.5 mM caffeine markedly enhanced motility and improved the SPA results. After 30 minutes' exposure, the motility was 45% +/- 5%, with all spermatozoa exhibiting progressive movement. This stimulation was maintained over a 24-hour period. When caffeine was present during the 2-hour preincubation for the SPA, penetration rates increased to 50% +/- 10% (P less than 0.05). These results demonstrate that the poor-quality sperm retrieved from a human alloplastic spermatocele can be improved with exogenous stimulation and suggest that their fertilizing capacity may be enhanced by this treatment. PMID- 4029430 TI - The effect of relaxin on the motility of sperm in freshly thawed human semen. AB - In an attempt to improve the motility of thawed spermatozoa after 1 week of its being frozen, we treated ten normal semen samples with 16.7 nmol relaxin and 6 mmol caffeine. Motility and grade of forward progression were examined after thawing. Caffeine significantly improved motility of spermatozoa. Relaxin, when added to semen at the time of thawing, improved motility and grade of forward progression significantly. This effect was not seen if relaxin was added before freezing. These results suggest that the biologic activity of relaxin is adversely affected by freezing and thawing in seminal plasma. These observations may have clinical importance for the improvement of motility of frozen spermatozoan samples at the time of artificial insemination and for the possible improvement of pregnancy rates. PMID- 4029431 TI - Improved semen quality after a short-interval second ejaculation. PMID- 4029432 TI - Absorbable external rings for anastomosis of the fallopian tubes: a feasibility study. AB - A novel approach to tubotubal anastomosis with external, absorbable, ring-shaped devices was evaluated. Fallopian tubes of female Sprague-Dawley rats were transected and coagulated and either left divided or anastomosed with microsurgical technique, with or without external rings. Postoperative patency and pregnancy rates were used to evaluate the procedures. Transected and coagulated fallopian tubes remained occluded at the time of repeated surgery, and no implantations were observed in the corresponding uterine horns. Of ten fallopian tubes anastomosed without the ring, five were patent and five were partially blocked. All ten fallopian tubes anastomosed with the external rings were fully open. Implantation sites were observed in four of ten uterine horns corresponding to fallopian tubes anastomosed without the ring and in eight of ten horns anastomosed with the external ring. The difference was statistically significant, P = to 0.03. All external rings were completely absorbed 7 weeks after anastomosis. The new technique was simpler to perform and was less time consuming. We conclude that tubotubal anastomosis with external rings may offer advantages over the conventional technique. PMID- 4029433 TI - A modified technique for aspiration of oocytes from human ovarian follicles. PMID- 4029434 TI - Infertile men and in vitro fertilization therapy. PMID- 4029435 TI - [Spontaneous and evoked activity of neurons of the deep structures of the brain in response to anodal polarization]. AB - In cats, the effect of anodal polarization on the spontaneous unit activity of the caudate nucleus, MGB, center median and on the evoked unit activity of the MGB during sound stimulation, was studied. The polarization (300-500 microA for 1 3 min, at the distance up to 3 mm from the polarizing electrode) caused a reversible inhibition of the spontaneous and evoked unit activity followed by a prolonged aftereffect: inhibition of the spontaneous discharges for 4-10 min and disappearance of the evoked unit responses for 5-20 min. PMID- 4029436 TI - [Steady potential dynamics in hypothalamic structures in response to a tolerogen and an immunogen]. AB - DC potential shifts due to induction of immune tolerance and immune memory were studied in hypothalamic structures. The lost capability of immune cooperation after tolerogen administration was accompanied by a monophasic negative shift of DC potential. Immunogen administration induced a positive shift of DC potential within 1-3 days. An immunogen fraction induced a pyrogenic response. There seems to be a correlation between the pyrogenic and immunogenic actions of antigens and the reorganization of hypothalamic neurons function. PMID- 4029437 TI - [Oscillating potentials of the retina and superior colliculi and correlations with neuronal activity]. AB - The oscillatory potentials of retina and superior colliculus induced with photostimuli were studied in unanesthetized rabbits. Increasing intensity of light flashes induces a better correlation of the responses in these structures. A common genesis of the oscillatory processes and neuronal activity was revealed. The peculiarities of formation of the short-latency responses in the superior colliculus and the specificity of generation of the responses of photostimuli of extreme brightness, are discussed. PMID- 4029438 TI - [Overall synchronized response of the inferior colliculi to lateralization of complex sounds]. AB - Interaural differences in time, intensity or phase introduced into a different frequency component of complex sounds results in changes of amplitude and form of the frequency following response depending on the frequency and phase ranges of the sounds. This relationship may be due to physical differences in stimulation of both ears, i. e. to differences in the sound wave forms and, consequently, in conditions of the convergence of both monaural afferent inflows. PMID- 4029439 TI - [Changes in intraocular pressure in response to experimental testing of the amygdaloid complex]. AB - Prolonged electrical stimulation of the lateral amygdaloid nucleus increased the intraocular pressure, the secretion of the intraocular fluid and the amount of proteins and glycosaminoglycans in it. Bilateral electrolysis of the lateral amygdaloid nucleus caused a resistant decrease of the intraocular pressure due to reduced secretion and to increase of the outflow coefficient of the intraocular fluid. PMID- 4029440 TI - [Effect of sympathetic denervation on the outflow of intraocular fluid and the concentration of pyrocatechins in the fluids and tissues of the eye]. AB - After removal of the supper cervical sympathetic ganglion in cats followed by increase of the intraocular pressure from 20 to 32 mm Hg, the outflow of intraocular fluid was sharply enhanced due to lowering tone of tissues of the eye drainage apparatus in the desympathised eye. Noradrenaline was found to reduce sharply by the 4th-5th day in the desympathised eye's tissues due to degenerative processes whereas accumulation of noradrenaline by the 6th-8th day occurred on account of humoral factors. PMID- 4029441 TI - [Background activity of neurons of the tracheal plexus in the rat]. AB - Morphological structure of the nerve plexus of the rat tracheal dorsal muscle wall is described and electrophysiological data on neuronal activity of this plexus are presented. Extracellular recording revealed two types of spontaneous activity including a single-spike type and a serial-spike type. The presence of excitatory and inhibitory interaction between neurons of a single ganglion is shown. Characteristic features of the tracheal part are discussed in comparison with other parts of the metasympathetic system. PMID- 4029442 TI - [Effect of temperature on heterometric autoregulation of the heart]. AB - In heart-lung preparation of cats, the heart load was increased 1.5-fold. The cooling from 38 degrees C to 25 degrees C did not affect the relative changes of hemodynamics under the load which suggests physical nature of the main links of heterometric autoregulation. On the other hand the data obtained show a certain commonness of Starling's law and Anrep's phenomenon as different manifestations of this regulation. PMID- 4029443 TI - [Oxygen tension in the intact and neuronally-isolated cortex]. PMID- 4029444 TI - [Effect of reserpine on inhibition of preganglionic neurons induced by stimulation of the vagus nerve]. PMID- 4029445 TI - [Effect of several anticholinesterase agents on the permeability of ocular vessels in the rabbit]. PMID- 4029446 TI - [Membrane potential fixation using an oscillograph]. PMID- 4029447 TI - A patient with progressive monoarticular arthritis: medical grand rounds at the Medical Center of Delaware. PMID- 4029448 TI - Group G streptococcal arthritis associated with adenocarcinoma of the colon. PMID- 4029449 TI - Alcoholic ketoacidosis in pregnancy: a case report and review. PMID- 4029451 TI - Lyme disease. PMID- 4029450 TI - Treatment of acute exacerbation of chronic respiratory failure with doxapram: a case report. PMID- 4029452 TI - Let's set the record straight. PMID- 4029453 TI - Cardiovascular effects of tobacco abuse. PMID- 4029454 TI - Cigarette smoking and lung cancer: a modern tragedy. PMID- 4029455 TI - Achieving a smoke-free society. PMID- 4029456 TI - Smoking during pregnancy. PMID- 4029457 TI - Immunomodulation of experimental malaria by MDP. PMID- 4029458 TI - Incrimination of Anopheles minimus Theobald and Anopheles balabacensis balabacensis Baisas (A. dirus) as malaria vectors in Mizoram. PMID- 4029459 TI - Studies on the incidence of malaria in Gadarpur town of Terai, Distt. Nainital, U.P. PMID- 4029460 TI - Contact sensitivity in children and adults with atopic dermatitis--a chronological study. AB - 61 atopic dermatitis patients were subjected to a second patch testing 3-15 years (average 7.3 years) after the first contact sensitivity examination. The comparison between the results of the two studies revealed that 26.2% of patients had been sensitive to one or more haptens at the first patch testing and that 24.6% reacted positively at the second. 9 subjects (14.8%) still manifest contact sensitivity, while 6 (9.8%) reversed to positivity and 7 (11.5%) to negativity. The chemicals most frequently involved were nickel sulphate, potassium dichromate, benzoyl peroxide, diphenylguanidine. This study demonstrates that contact reactions are not linked to susceptibility to skin irritants in atopic dermatitis patients and that they tend to increase with time. PMID- 4029461 TI - Prednisolone pulse therapy for childhood systemic lupus erythematosus with prominent dermatomyositis. A case report. AB - A 10-year-old boy with systemic lupus erythematosus exhibiting prominent features of dermatomyositis has been treated with 600 mg prednisolone intravenously per day on 3 consecutive days. Clinical and serologic improvement started after the first course of pulse therapy, and was remarkable during a second course. Basic treatment using oral prednisolone is recommended. PMID- 4029462 TI - Comparison of the short-duration dithranol and Dithrocream therapy in the treatment of psoriasis. AB - Short-duration dithranol therapy (SDDT) was compared to Dithrocream therapy in an open trial for the treatment of psoriasis. SDDT is based on the application of highly concentrated (1-2%) dithranol (anthralin) for a short period of time (10 20 min) and appeared to be clearly less staining and more comfortable than Dithrocream (0.1-0.5%). Both treatment methods appeared to be clinically effective; the SDDT method was slightly more effective than Dithrocream in this study. PMID- 4029463 TI - Repigmentation of vitiligo macules treated topically with Efudix cream. AB - Repigmentation has been observed under the influence of topically administered Efudix cream in 3 patients with vitiligo of symmetrical acral type. No response has been received in 2 patients with segmental vitiligo treated in the same way. Recurrence of vitiligo was seen in 1 patient. Histologic and electron microscopic characterization of recolonized melanocytes is described. The significance of topical 5-fluorouracil treatment in vitiligo is discussed. PMID- 4029464 TI - Purpuric vasculitis due to tartrazine. PMID- 4029465 TI - Cell cycle time and life-span of cells in the mouse eye. Measurements during the postfetal period using repeated 3H-thymidine injections. AB - In this investigation the cell cycle time and the life-span of cells in different tissues of the mouse eye were determined during postfetal development not with single but, instead, by means of repeated 3H-thymidine injections. The potential of this method applied for the first time in the mammalian eye, is thoroughly discussed. Essentially, four groups of 19-21 mice each, aged 1, 10, 20, and 60 days at the start of the experiment, received intraperitoneal injections of 3H thymidine at a dose of 1 microCi/g body weight every 4 h for a maximum of 14 days, i.e. a total of up to 85 injections. Further animals were sacrificed after the 13th, 19th, 25th, 31st, 37th, 49th, 61st, 73rd, and 85th injections, i.e. 2, 3, 4, 5, 6, 8, 10, 12, and 14 days after the start of the experiment. When all the injections had been given, animals from each group were sacrificed on the 1st, 4th, 8th, 16th, and sometimes the 32rd, 48th, and 64th days, respectively, after the last injection. With this experimental paradigm it was possible: (1) to determine the cell cycle time and the life-span of the cells during postfetal development up to maturity without gaps; (2) to establish the end of the development by means of cell proliferation in various tissues of the mouse eye; herewith it was possible to determine the times at which the development by cell proliferation is replaced by development by cell differentiation, and (3) to clearly prove in which mature ocular tissues cell turnover still exists and in which it does not; this appears to be especially important, since in recent years the importance of cell proliferation process following injury and stimulation was also recognized in the eye, for example, in massive periretinal proliferation in connection with retinal detachment and retinal surgery, as well as in endothelial injuries following intraocular lens implantation; only when normal conditions are known can pathological proliferative processes be recognized as such and be distinguished from normal ones. The results are cumulatively represented in tabular form, from which details are to be extracted. As expected, cell cycle times are very short and seemingly homogeneous in tissues which develop within themselves, but become longer and inhomogeneous, except in the inner and outer granular layer of the retina, in which the cell proliferation comes to a particularly abrupt end. The shortest cell cycle time occurred in the cells of the vascular walls of the retina at the time of birth and was 24 h.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 4029466 TI - Evidence of early impairment of parasympathetic reflexes in insulin dependent diabetics without autonomic symptoms. AB - Cardiovascular (CV) autonomic functions were assessed in 50 insulin-dependent diabetic patients and in 30 controls using a battery of autonomic tests: Valsalva Manoeuvre (VR), Deep Breathing (DB), Lying-to-Standing (LS), Sustained Handgrip (SHG) and Postural Hypotension (PH). The results were compared with those obtained from a study of cardiac resting adjustment to different static postures (quiet lying and standing). 10 diabetics with abnormal responses to the majority of tests were considered affected by Diabetic Autonomic Neuropathy (DAN); 15 with some abnormal of borderline responses were defined much less than Borderlines much greater than. The remaining 25 diabetics, while displaying lower values than the controls in parasympathetic tests, had much less than normal much greater than autonomic responses. The VR mean (+/- SD) value was 1.71 +/- 31 in much less than normal much greater than diabetics and 2.01 +/- 0.29 in controls (p less than 0.001); the DB mean value was 20.6 +/- 87 and 28 +/- 8.13 (p less than 0.001), and the LS mean value 1.16 +/- 0.12 and 1.33 +/- 0.18 (p less than 0.001) respectively. No significant differences were found in the sympathetic tests (SHG, PH). However Heart Rate (HR) adjustment of diabetics with normal CV responses to immobile standing (RR mean 783 +/- 136 ms) and lying (RR mean increment of 25 +/- 11%; p less than 0.001) was similar to that of controls who had a resting HR standing (RR mean 749 +/- 104 ms) and lying (RR mean 884 +/- 116 ms) with a mean increment of 20.2 +/- 10.9% (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4029467 TI - Microheterogeneity of serum glycosyl albumin in diabetes mellitus. AB - Proteins purified by affinity chromatography on Blue-Sepharose CL-6B from serum of 10 normal controls and 19 Type I diabetic patients were studied by means of combined ultrathin isoelectric focusing and photochemical silver stain. While only a single band of protein (characterized as albumin by crossed immunoelectrophoresis) with a pI of 4.7 was found in serum of normal subjects, 10 out of the diabetic group showed some bands of proteins with a pI greater than 4.7 and a single one with a pI less than 4.7. Concanavalin A-Sepharose removed all these bands with altered pIs which were further characterized as albumin by fused rocket immunoelectrophoresis of the eluates from Concanavalin A-Sepharose, direct immunofixation after isoelectric focusing of proteins with high purified anti-albumin antibodies, SDS-polyacrylamide gradient pore electrophoresis, aminoacidic analysis. The gas-chromatographic analysis of carbohydrates released from both the albumin bound to Concanavalin A-Sepharose and that not bound, revealed in addition to two unidentified peaks, the presence of glucose, galactose and mannose whose contents were greatly increased in albumin with affinity for the lectin. Serum glycosyl albumin concentration was not statistically different in serum of diabetic patients displaying cationic glycosyl albumin in comparison to patients without these proteins (0.2261 +/- 0.0186 versus 0.1874 +/- 0.015 nmole HMF/nmole albumin), whereas the first group showed statistically higher urinary excretion rates of albumin (28.6 +/- 1.2 micrograms/min versus 4.6 +/- 0.2 micrograms/min).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4029468 TI - Nutritive toe skin capillaries in middle-aged patients with diabetes mellitus. AB - Vital capillary microscopy was employed in a study of the toe dorsum capillaries in 92 middle-aged diabetics and 96 controls of similar age and sex distribution. As a general finding most vision fields in the same toe showed an almost identical capillary pattern. In 17% of the toes in the controls compared to about 35% of the toes in the patients the capillaries were dilated more than 3 times. Such findings were unrelated to blood glucose control and a number of metabolic variables. In the patients with non-insulin dependent diabetes an abnormal capillary pattern was particularly common in patients with evidence of obstructive arterial disease. Such a relationship was not observed in patients with insulin-dependent diabetes in whom changes in the capillary pattern to a higher extent may be related to other mechanisms such as neuropathy. PMID- 4029469 TI - Increased labile hemoglobin glycosylation in opiate addicts: an unclear phenomenon. PMID- 4029470 TI - [Should the idea of prediabetes be revived?]. PMID- 4029471 TI - [French Language Association for the Study of Diabetes and Metabolic Diseases. Rennes, 19-20 April 1985. Spring meeting. Abstracts]. PMID- 4029472 TI - Chronic villitis of unknown etiology and maternal arterial lesions in preeclamptic pregnancies. AB - Placental lesions from 361 singleton full-term pregnancies were studied. These placentas were divided into two major groups: the study group consisting of 146 placentas from mothers with pregnancy-induced hypertension and a normotensive control group, which included 215 placentas from mothers with normal pregnancies. Each group was divided into three subgroups according to the allocation of infant's birthweight in the normal ponderal curve. A statistically significant higher incidence and severity of villous lesions was observed in placentas of mothers with pregnancy-induced hypertension when infants were over the 25th centile of the ponderal curve. Vascular lesions, i.e., absence of physiological changes in spiral arteries of the placental bed, acute atherosis and chronic vasculitis-like lesions were also more frequently observed in the hypertensive group than in controls. These placental lesions have been described in placentas of small for gestational age infants with or without maternal hypertension and in those of preeclamptic women with appropriate for gestational age infants. Since acute atherosis-like lesions have been reported in placentas of pregnant women with systemic lupus erythematosus and in rejected renal transplants, a possible maternal immunological reaction against fetal tissues could be responsible for the pathogenesis of these entities. PMID- 4029473 TI - Maternal attitudes to fetal monitoring. AB - During a randomized clinical trial concerning alternative methods of intrapartum fetal surveillance (electronic fetal monitoring (EFM) and auscultation (AUS)) an investigatory interview was carried out. Out of 655 expecting mothers the antepartum preference of EFM was 39.5%, of AUS 32.3% and 28.1% were undecided (UD). EFM was especially preferred by obstetrical high-risk patients. Reasons for preference of AUS were a natural childbirth, a non-technological milieu, and the lack of supposed discomfort from sensors and belts. The pregnant women found as major advantages of EFM continuous observation and the possibility of quick intervention. Postpartum 385 patients were again interviewed. The majority upheld the original preference if that method was used. If the non-preferred method had been applied many would stick to the primary preference although a tendency to prefer the experienced method was seen. The patients who antepartum preferred AUS, but had EFM, became more positive toward the method, and a significantly increased number were positively influenced by the EFM signal/trace and found the method promoting their partner's involvement in labor. Enforced immobility, however, was a major disadvantage as well as the technical milieu. If EFM is to be accepted by a majority of women giving birth it is necessary to increase the pregnant women's knowledge of the method and to take milieu factors into consideration in order to reduce the intrinsic depersonalization of EFM. PMID- 4029475 TI - Cervico-isthmic pregnancy ending with the delivery of a live-born infant in late second trimester. AB - A very rare case of cervico-isthmic pregnancy, terminated by cesarean section in late second trimester with the delivery of a live-born infant who subsequently remained alive, is described. The authors suggest that this is the first case of neonatal survival in late second trimester of a cervico-isthmic pregnancy. PMID- 4029474 TI - Genital infections in women undergoing therapeutic abortion. AB - We studied the prevalence of genital infections and the frequency of infectious complications in 170 women who requested an abortion in Antwerp, Belgium, where termination of pregnancy is still illegal. Chlamydia were isolated in 12% of these women, compared to a 0.6% isolation rate for N. gonorrhoeae. After the abortion 5.5% developed PID and 3% endometritis. There was a strong correlation between an infection with C. trachomatis before abortion and the appearance of infectious complications after the aspiration curettage. No such relationship was found with any other micro-organism. Depending on the prevalence of C. trachomatis in a given population, screening followed by selective treatment or prophylactic use of antimicrobial medication for all women is indicated to prevent post-abortum infections. PMID- 4029476 TI - A cell line, ROSE 199, derived from normal rat ovarian surface epithelium. AB - A cell line, ROSE 199, derived from rat ovarian surface epithelium (ROSE) formed papillary structures which resembled, histologically, serous papillary cystadenomas of borderline malignancy seen in the human ovary. Crowded cultures produced two layers of cells separated by a thick layer of collagen fibers. Such cultures shed viable cells into the growth medium, while no cells were shed by short-term ROSE cultures. The resemblance to ovarian tumors exhibited by ROSE 199 cells in culture, reinforces the hypothesis that the common epithelial tumors of the ovary are derived from the ovarian surface epithelium. ROSE 199 cells, while retaining their epithelial morphology and ultrastructural characteristics, express stromal activity such as abundant collagen production. Perhaps this ability to express epithelial and stromal behavior is a contributing factor to the ready neoplastic transformation of the ovarian surface epithelium. PMID- 4029478 TI - Dose-dependent effect of 17 beta-estradiol determined by growth curves and flow cytometric DNA analysis of a human breast carcinoma (T61) grown in nude mice. AB - An estrogen and progesterone receptor-positive human breast carcinoma (T61) grown in nude mice was exposed to 1.0, 0.1, 0.01, and 0.001 mg 17 beta-estradiol. These doses resulted in serum peak concentrations (day 1) of estradiol ranging from 3.5 X 10(-8) to 6.9 X 10(-10) M. The effect of the treatment was evaluated using growth curves and flow cytometric DNA analysis. The treatment induced a dose dependent growth delay and dose-dependent changes in the cell cycle distribution. The cell cycle changes comprised a decrease in the G1 phase, an accumulation of cells in the S phase, and an increasing fraction of polyploid cells. The results suggest that estradiol induces a dose-dependent cell killing effect in the T61 human breast carcinoma. The correlation between the treatment-induced growth delay and the effect on the cell cycle distribution indicates that the changes in the cell cycle are a reflection of the estradiol-induced cell destruction. Since no tumor growth stimulation could be observed even at very low serum estradiol concentrations, the T61 human breast carcinoma may represent a new aspect in the study of human breast cancer. PMID- 4029477 TI - Hapten binding assay using guinea pig macrophages. AB - An assay for testing the binding of haptens to antigen-presenting cells was developed. The test consists of consecutive incubation of macrophages with the tested hapten, followed by incubation with a radioactively labeled standard. If the first hapten occupies a certain number of binding sites, the other one (radioactively labeled standard) reveals reduced binding. The binding assay in the present modification is fully suitable for measuring the binding of water soluble haptens. It was found that from a panel of tested haptens, DNFB, beta bromostyrol and phenylacetaldehyde exhibit strong binding. PMID- 4029479 TI - Differentiation of chick blood island erythroblasts into erythrocytes and stability in long-term culture. AB - Clusters of 20-70 erythroblasts from blood islands of early chick blastoderm were cultured in serum-free chemically defined medium for a 3-month period. The erythroblast cluster produces erythroid cells and hemoglobins characteristic of the primitive and definitive erythroid cell lines. It seems there is a progenitor erythroid cell(s) in the erythroblast cluster which starts and/or continues maturing along various pathways of hemopoietic differentiation under simple culture conditions. The erythroid character of these cells is stable during the 3 month culture period. PMID- 4029480 TI - Nutrition and somatomedin--XII. Fractionation of somatomedins and somatomedin inhibitors in normal and diabetic rats. AB - Bioassayable somatomedins and somatomedin inhibitors were examined after chromatographic separation, using serum from normal rats (enriched in somatomedins) and diabetic rats (enriched in somatomedin inhibitors). At neutral pH, gel filtration on Sephacryl S-300 revealed somatomedins at mol. wt approximately 140,000 (presumably carrier-bound) and inhibitors at mol. wts approximately 250,000, approximately 24,000 and approximately 1,000. At acid pH, gel filtration on Sephadex G-50 revealed somatomedins at mol. wt approximately 8,000 (presumably carrier-free) and a single inhibitor at mol. wt approximately 21,000. Ion exchange chromatography revealed that the inhibitor(s) may be more acidic than the somatomedins, but only low quantities of somatomedins were recovered. Sephadex G-50 fractionation was applied to pathophysiologic models in rats: 3 days of fasting were associated with a 62% fall in somatomedins and a 159% rise in inhibitors; 2 days of diabetes were associated with a 60% fall in somatomedins and a 344% rise in inhibitors. Since chromatography on Sephadex G-50 at pH 2.4 appears to provide adequate separation of somatomedins and somatomedin inhibitors with good estimated recovery of biological activity, this simple approach may be a probe useful in examining the regulation of somatomedins and somatomedin inhibitors in vivo. PMID- 4029481 TI - Cyanopyrazoles as analogs of purine precursors--II. Effects on macromolecular synthesis and cell cycle progression. AB - The cytotoxic and cytokinetic effects, and in vitro inhibition of macromolecular synthesis by cyanopyrazoles were studied using Friend leukemia and Ehrlich ascites tumor cells. At concentrations in the range of 2.5 mM to 50 microM analog 3(5)-amino-4-cyano-5(3)-trichloromethylpyrazole (I) was highly cytotoxic and completely inhibited thymidine, uridine and leucine incorporation into macromolecular material. 24 hr incubation of FL cells with cytostatic concentrations of compound I (in the range of 2 to 0.5 microM) resulted in an accumulation of cells in the G2 + M phase. Analogs N-hydroxyethyl-3(5)-amino-4 cyano-5(3)-trichloromethylpyrazole (II) and 3(5)-amino-4-cyanopyrazole (III) were not cytotoxic at concentrations up to 5 mM and did not substantially inhibit precursor incorporation into macromolecules but exhibited a cytostatic activity. These compounds caused a decrease of FL cells in the G2 + M phase and an accumulation in the S phase. Analogs I and II displayed a similar in vivo inhibitory effect on thymidine incorporation into DNA in EAT cells. The results indicate that the cytotoxicity of cyanopyrazoles correlates with their ability to inhibit precursor incorporation into macromolecular material. On the other hand, the cytostatic action of compound I is not coupled to a block of nucleic acid synthesis. PMID- 4029482 TI - Effects of phospholipids on the specific binding of [3H]spiroperidol to the cholate extract of rat brain synaptic membranes. AB - Effects of phospholipids including PC, PE, PI, and PS on the specific [3H]SPD binding to the solubilized dopamine receptors were examined in the cholate extracts of the cortical and striatal synaptic membranes (P2M) of the rat brain. PC and PS, but not PE or PI, at 0.4 mM greatly enhanced the specific [3H]SPD binding to the cholate extracts of both cortical and striatal P2M fractions. PC and PS did not enhance the specific [3H]DA binding to the same cholate extracts. The enhancing effects of PC and PS were temperature-dependent and in a dose response manner peaking at 0.4 mM and 0.2 mM respectively. Such temperature dependence indicated that the PC effects were not due to trapping of [3H]SPD by PC but represented a possible DAR-PC complex formation that allowed higher binding for the ligand. Failure of natural cerebellar P2M in enhancing the [3H]SPD binding to the cholate extract supports the notion that fluidity of the phospholipids is required for the binding or the formation of the DAR-PC (or PS) complex. Scatchard analysis of the [3H]SPD binding to the cholate extract in the absence or presence of PC or PS indicated that the PC or PS enhancement of the ligand binding may be mainly due to an increase in the number of binding sites since both PC and PS significantly increased the Bmax but not the Kd of the binding. PMID- 4029483 TI - Glucose turnover in adult non-growing tumour-bearing mice. AB - [6-3H]glucose was used for measurements of plasma glucose turnover in adult non growing mice with sarcoma-induced malnutrition. Plasma glucose turnover was increased in freely-fed tumour-bearing mice but not in starved tumour-bearing mice. Elevated glucose turnover in freely-eating sarcoma-bearing mice was associated with an increased glucose pool, the latter not only being due to an expanded distribution volume of glucose. Plasma lactate was elevated in sarcoma bearing mice independently of their food intake. The results show that elevated plasma glucose turnover in an anorectic tumour-bearing host is not due to insufficient adaptation to food depression. Increased glucose turnover in tumour bearing mice was associated with an altered intermediary whole body metabolism of glucose which is not entirely accounted for by the state of malnutrition of the host. PMID- 4029484 TI - The isolation, characterisation and kinetics of glutathione-S-transferase from human platelets. AB - Glutathione S-transferase activity from human platelets was purified to homogeneity by affinity chromatography. The purified enzyme was found to be the acidic form and its molecular and catalytic properties were identical to acidic glutathione S-transferases purified from other human tissues. The purified platelet enzyme had no peroxidase activity and did not protect microsomes against peroxidation. PMID- 4029485 TI - Artificial and natural thermostabilization of subunit enzymes. Do they have similar mechanism? AB - Rabbit skeletal muscle glyceraldehyde-3-phosphate dehydrogenase was stabilized by intramolecular intersubunit crosslinking with diimidoesters. Half-inactivation temperature for optimal cross-linker-treated enzyme preparation increased by 11 degrees C. Stabilization effect correlated with the content of crosslinked fractions in enzyme preparation, as proved by SDS gel-electrophoresis. It is proposed that artificial crosslinks stabilize the enzyme in a similar fashion to salt bridges in the thermophilic bacteria enzymes, i.e. preventing dissociation into inactive subunits. PMID- 4029486 TI - Characterization of a nitrilase from Nocardia sp. (Rhodochrous group) N.C.I.B. 11215, using p-hydroxybenzonitrile as sole carbon source. AB - The purification and properties of an enzyme from Nocardia sp. which catalyses the conversion of p-hydroxybenzonitrile to p-hydroxybenzoic acid and ammonia without intermediate formation of the amide is described. The enzyme displayed a broad pH optimum between 7.0 and 9.5 and exhibited Michaelis-Menten kinetics with Km of 1.27 mM for p-hydroxybenzonitrile. The 12-unit multimeric enzyme possessed a mol. wt of 560,000 and was sensitive to thiol-specific reagents. Although aliphatic nitriles were not substrates for the enzyme a broad range of substituted aromatic nitriles were attacked with a general preference being shown for those with meta substitution. PMID- 4029487 TI - Glucose infused through the portal vein enhances liver gluconeogenesis and glycogenesis from [3-14C]pyruvate in the starved rat. AB - After a pulse of [3-14C]pyruvate, 24 hr starved rats were infused through the portal vein with two different doses of glucose (7.8 or 20.8 mg/min) or the medium, and blood was collected from the inferior cava vein at the level of the suprahepatic veins. The highest dose of glucose enhanced the appearance of [14C]glucose in blood from the 2nd to the 20th min after tracer delivery. It also enhanced production of [14C]glycogen and concentration of glycogen in the liver after 5 and 20 min. At 20 min of glucose infusion the appearance of [14C]glyceride glycerol in liver as well as liver lactate concentration and lactate/pyruvate ratio were increased. The low dose of glucose used enhanced liver values of [14C]glycogen, [14C]glycogen specific activity and glycogen concentration. Our results support the hypothesis that in the starved rat glucose is converted into C3 units prior to being deposited as liver glycogen and based on the liver zonation model (Jungermann et al., 1983) it is proposed that glucose stimulated gluconeogenesis by shifting the liver to the cytosolic redox state as a secondary consequence of increased glycolytic activity. PMID- 4029488 TI - The amino acid sequence of protein CM-3 from Dendroaspis polylepis polylepis (black mamba) venom. AB - Protein CM-3 from Dendroaspis polylepis polylepis venom was purified by gel filtration and ion exchange chromatography. It comprises 65 amino acids including eight half-cystines. The complete amino acid sequence of protein CM-3 has been elucidated. The sequence (residues 1-50) resembles that of the N-terminal sequence of the subunits of a synergistic type protein and residues 51-65 that of the C-terminal sequence of an angusticeps type protein. Mixtures of protein CM-3 and angusticeps type proteins showed no apparent synergistic effect, in that their toxicity in combination was no greater than the sum of their individual toxicities. PMID- 4029489 TI - Effect of assay temperature on the kinetics of 3-hydroxy-3-methylglutaryl coenzyme A reductase in rat liver and Morris hepatoma 5123C. AB - A procedure is described for the assay of 3-hydroxy-3-methylglutaryl CoA reductase (HMG-CoA reductase) in a large number of samples with minimal benchwork and within a 24-hr period. The Michaelis constants for HMG-CoA reductase were determined for microsomal enzyme from the liver of normal and cholesterol-fed rats and Morris hepatoma 5123C. The apparent Km D-HMG-CoA was ca. 3.5 microM and was not affected by assay temperature or cholesterol feeding. The apparent Km NADPH for microsomal HMG-CoA reductase was 10-15 microM and similarly was not affected by assay temperature. The Arrhenius plot parameters (activation energy and transition temperatures) were the same whether determined using the reaction velocity from fixed substrate concentrations or V from subtraction curves. This confirmed that values obtained using fixed saturating substrate concentrations are valid and not affected by a temperature-dependent alteration in the affinity of the enzyme for its substrates. PMID- 4029490 TI - Interference by ethanol of coupling between gluconeogenesis and ureagenesis from proline in isolated hepatocytes. AB - Proline stimulated equally the production of glucose and urea by isolated hepatocytes. Ethanol suppressed glucose production much more strongly than urea synthesis. The proline-derived carbon not reaching glucose was found as lactate. Inhibition of phosphoenolpyruvate synthesis with 3-mercaptopicolinate blocked gluconeogenesis, but was without effect on lactate production. Acetate was formed from endogenous sources, as well as from ethanol. Its accumulation from ethanol was enhanced both by proline and lactate. The differential effect of ethanol on gluconeogenesis and ureagenesis appears to be related to its effect on the redox state of the cell. PMID- 4029491 TI - The effect of lactation on the fractional synthetic rate of protein in the liver and muscle of rats. AB - Protein synthesis in muscle and liver were studied in rats in early and peak lactation. While the fractional synthetic rate of liver was greatly enhanced there were no significant changes in muscle. No evidence was obtained for a marked contribution of muscle protein for the demand of lactation. PMID- 4029492 TI - The effect of glucagon on N-acetylglutamate-synthetase. AB - The effect of glucagon and the protein content of the diet on the activity of N acetylglutamate synthetase was studied. The activity of N-acetylglutamate synthetase depended on the protein content of the diet. Glucagon increased the activity of N-acetylglutamate synthetase and reduced the stimulatory effect of arginine. The enzyme of glucose-fed animals became arginine independent. It was concluded that glucagon induced some kind of covalent modification of the synthetase. PMID- 4029493 TI - Effect of clofibrate treatment on aconitase activity in rat liver and other tissues. AB - The activity of both mitochondrial and cytosolic aconitases was significantly increased in the livers of male rats following treatment with the hypolipidemic drug clofibrate. Cycloheximide or puromycin administration to rats inhibited the inducing effect of clofibrate on the enzyme activity. Aconitase activity in small intestine homogenate was also increased by clofibrate. The drug did not affect the enzyme activity in rat kidney, heart and brain. PMID- 4029495 TI - Carnitine palmitoyltransferase deficiencies. PMID- 4029494 TI - N-terminal sequence of creatine kinase from skeletal muscle of rabbit and rhesus monkey. AB - The first 20 amino acids from the N-terminus of skeletal muscle (MM) creatine kinase from both rabbit and rhesus monkey have been identified and these sequences show considerable homology. Contrary to an earlier report, the N terminus was not found to be blocked. Both of these sequences show much less homology with the N-terminal sequence of heart muscle (MM) creatine kinase and no homology with that of the heart muscle mitochondrial (MiMi) isozyme. No homology was found between the N-terminal sequence of the mitochondrial isozyme and the URF (unidentified reading frame) proteins of the human mitochondrial genome, indicating that the mitochondrial enzyme is encoded by nuclear genes. This suggests the possibility that an N-terminal peptide may be cleaved from the mitochondrial isozyme on its translocation across the mitochondrial membrane. PMID- 4029496 TI - Investigation of human mitochondrial myopathies by phosphorus magnetic resonance spectroscopy. PMID- 4029497 TI - Mechanisms involved in hormone signal transduction across the mitochondrial membrane. PMID- 4029498 TI - Hormonal control of intramitochondrial Ca2+-sensitive enzymes in heart, liver and adipose tissue. PMID- 4029499 TI - On the hormonal control of heart mitochondrial Ca2+. PMID- 4029500 TI - Control of polypeptide chain initiation by sugar phosphates. PMID- 4029501 TI - Translational control by amino acids and aminoacyl-tRNA synthetases in cultured mammalian cells. PMID- 4029502 TI - Computer graphics of large macromolecules. PMID- 4029503 TI - Further characterization of substratum influence on PC12 cell shape and dopamine processing. AB - We recently demonstrated that PC12 cells cultured on extracellular matrix (ECM) exhibit a flattened morphology, release more dopamine and contain less intracellular dopamine than cells which have a rounded shape on plastic culture ware. To further explore the role of PC12 cell shape in dopamine processing, we characterized the interaction of ECM and various agents on cell shape and dopamine release and content. In addition, the constituents of the ECM and the corneal endothelial cells which produce the ECM were presented in soluble form to PC12 cells on plastic. The soluble polysaccharides heparin, dextran and dextran sulfate, caused a dose-related increase in rounded (refractile) cells on ECM, a dose-related decrease in dopamine release and an increase in dopamine content relative to flattened cells on ECM. Chondroitin sulfate and hyaluronic acid did not prevent cell spreading on ECM nor affect dopamine processing. These experiments demonstrate that certain polysaccharides block cell spreading on ECM and that round cells on ECM secrete and store dopamine in a fashion similar to round cells on plastic. Colchicine, cytochalasin B and cycloheximide appear to affect dopamine synthesis and thus could not distinguish the role of cell shape in transmitter release. Treatment of PC12 cells on plastic with collagens I, II, III, IV, fibronectin, fibroblastic growth factor (FGF), or solubilized ECM had little effect on dopamine release or content. Endothelial cell conditioned medium and endothelial cell lysate increased dopamine release, but also increased dopamine content which differs from the effect of ECM. In summary, these experiments suggest that extracellular matrix alters cell shape and that the physical arrangement of these cells can determine dopamine secretion and storage. PMID- 4029504 TI - Use of a psoralen-induced phenocopy to study genes controlling spermatogenesis in Caenorhabditis elegans. AB - In the nematode Caenorhabditis elegans, spermatogenesis represents one of two alternative developmental pathways open to premeiotic germ cells. At least two genes, fem-1 and fem-2, control the initiation of spermatogenesis in XX (hermaphrodite) worms, and the entire spectrum of male differentiation in XO animals. Low-dose irradiation of worms treated with the light-activated DNA crosslinking drug trimethylpsoralen, at levels that do not affect cell division or growth rates, blocks spermatogenesis in C. elegans hermaphrodites and produces an identical phenotype to that of temperature-sensitive mutations in the fem genes. Psoralen treatment does not, however, produce corresponding phenotypes of these mutants in XO animals. The developmental age for phenocopy production is the same as the hermaphrodite temperature-sensitive period of the two mutants. The effects of pulses of restrictive temperature and psoralen treatment on fem-2 mutant hermaphrodites are additive, suggesting that psoralen crosslinking may reduce the level of the fem-2 gene product. Microbeam experiments localize the target for the psoralen effect to the primary germ cells in the first stage larvae, indicating that a critical step occurs in a small number of precursor cells prior to their commitment to spermatogenesis. PMID- 4029505 TI - Control of neural crest cell dispersion in the trunk of the avian embryo. AB - Many hypotheses have been advanced to explain the orientation and directional migration of neural crest cells. These include positive and negative chemotaxis, haptotaxis, galvanotaxis, and contact inhibition. To test directly the factors that may control the directional dispersion of the neural crest, I have employed a variety of grafting techniques in living embryos. In addition, time-lapse video microscopy has been used to study neural crest cells in tissue culture. Trunk neural crest cells normally disperse from their origin at the dorsal neural tube along two extracellular pathways. One pathway extends laterally between the ectoderm and somites. When either pigmented neural crest cells or neural crest cells isolated from 24-hr cultures are grafted into the space lateral to the somites, they migrate: (1) medially toward the neural tube in the space between the ectoderm and somites and (2) ventrally along intersomitic blood vessels. Once the grafted cells contact the posterior cardinal vein and dorsal aorta they migrate along both blood vessels for several somite lengths in the anterior posterior axis. Neural crest cells grafted lateral to the somites do not immediately move laterally into the somatic mesoderm of the body wall or the limb. Dispersion of neural crest cells into the mesoderm occurs only after blood vessels and nerves have first invaded, which the grafted cells then follow. The other neural crest pathway extends ventrally alongside the neural tube in the intersomitic space. When neural crest cells were grafted to a ventral position, between the notochord and dorsal aorta, in this intersomitic pathway at the axial level of the last somite, the grafted cells migrate rapidly within 2 hr in two directions: (1) dorsally, in the intersomitic space, until the grafted cells contact the ventrally moving stream of the host neural crest and (2) laterally, along the dorsal aorta and endoderm. All of the above experiments indicate that neither a preestablished chemotactic nor adhesive (haptotactic) gradient exists in the embryo since the grafted neural crest cells will move in the reverse direction along these pathways toward the dorsal neural tube. For the same reason, these experiments also show that dispersal of the neural crest is not directed passively by other environmental controls, since the cells can clearly move counter to their usual pathway and against such putative passive mechanisms.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 4029506 TI - Early events in insect neurogenesis. I. Development and segmental differences in the pattern of neuronal precursor cells. AB - The earliest events in the development of the central nervous system in insect embryos involve the differentiation of a stereotyped pattern of individually identified neuronal precursor cells, called neuroblasts (NBs), each of which generates a stereotyped family of neuronal progeny. After gastrulation, the midventral region of the ectoderm becomes a neuroepithelium; it is from this sheet of seemingly uniform ectodermal cells that certain cells enlarge to become NBs while the rest of the cells either die or acquire other nonneuronal phenotypes. Here we focus on three aspects of neurogenesis. First, we examine the morphological changes associated with the differentiation of neuronal precursor cells and nonneuronal support cells. The differentiation of each cell type is reflected by its morphology; moreover, the identity of individual cells of certain cell types (e.g., a particular NB) is reflected by their position within the neuroepithelium. Second, we show that there is a characteristic temporal sequence of differentiation in the stereotyped pattern of NBs. Third, we show that this stereotyped pattern of NBs varies in a segment-specific way by the addition or deletion of particular neuronal precursor cells. These studies on the events of early neurogenesis set the stage for the experimental manipulations described in the following paper (C. Q. Doe and C.S. Goodman, 1985, Dev. Biol. 110, 206-219). PMID- 4029507 TI - Early events in insect neurogenesis. II. The role of cell interactions and cell lineage in the determination of neuronal precursor cells. AB - The insect central nervous system (CNS) is composed of a brain and a chain of segmental ganglia; each hemiganglion contains about 1000 individually identifiable neurons. How is the enormous neuronal diversity and specificity generated? Neurons of a hemiganglion largely arise during embryogenesis from a stereotyped pattern of individually identified neuronal precursor cells, called neuroblasts (NBs). The transition from ectoderm to individual neurons thus involves two major steps: first, an undifferentiated ectodermal cell sheet produces the stereotyped pattern of 30 NBs per hemisegment; second, each of these NBs contributes a specific family of neuronal progeny to the developing CNS. We have used a laser microbeam to ablate individual cells in the grasshopper embryo in order to study the initial events of neuronal determination. In particular, how does a layer of apparently equivalent ectodermal cells produce a highly stereotyped pattern of unique NBs? Our results suggest the following mechanism for NB determination. (1) Cell interactions between the approximately 150 equivalent ectodermal cells of a hemisegment allow 30 cells to enlarge into NBs. (2) As these young NBs enlarge they inhibit adjacent ectodermal cells from becoming NBs; the adjacent cells then either differentiate into nonneuronal support cells or die. (3) Each NB is assigned a unique identity due to its position of enlargement within the neuroepithelium. (4) The NB then generates its characteristic family of neurons by an invariant cell lineage. Development of the insect CNS depends on cell interactions and positional cues to create a pattern of NBs, and then on cell lineage to restrict the fate of the NB progeny. PMID- 4029508 TI - Avian spinal cord chimeras. I. Hatching ability and posthatching survival in homo and heterospecific chimeras. AB - Quail-chick spinal cord chimeras were constructed by grafting isotopically, at the brachial level, the neural tube of a quail embryo into a chick of the same developmental stage. The chimeras were allowed to hatch and their behavior and survival after birth were observed. We found that if white Leghorns of the rapid feathering strain were taken as hosts, the ability of the operated embryos to hatch was higher than in the slow-feathering wild-type chickens. The important point arising from this study is that the establishment of the neuronal circuits and of the connexions of the grafted neurons to their peripheral and central targets occurs between cells of two different species in such a way that normal behavior of the chimera is ensured. These animals can stand, walk, and fly as normal chickens do. Moreover, the size reached by the fragment of quail spinal cord implanted into the chick axial structures is larger than it would have been in the donor at the same age. This results in perfectly normal morphogenesis of the vertebrae which develop from the chick somites at the level of the graft. The pigment pattern of the chick feathers colonized by quail melanoblasts of graft origin is very close to that of the quail, albeit somewhat different, probably due to the different size of the feathers in the two species. Normality of the chimeras is only transient. During the second month of their life they develop a neurological syndrome characterized first by the paralysis of the wings and later by their inability to stand. In strong contrast, spinal cord chimeras constructed between two histoincompatible chickens, remain healthy and seem to develop a complete tolerance to the graft. What seems to be the development of an immune rejection of the grafted neural tube in the quail-chick spinal cord chimeras is now under investigation. PMID- 4029509 TI - Activation of paternally derived regulatory mechanism in early mouse embryo. AB - A stage-specific occurrence of retrovirus-like elements (intracisternal particles) is regularly observed within the endoplasmic reticulum of early mouse embryos. A quantitative electron microscopic study was carried out on hybrid embryos issued from the matings between high- and low-producer mouse strains of intracisternal particles. The low-producer character behaved as dominant in all these crosses, and this enabled us to demonstrate the activation of paternally introduced regulatory mechanism in two-cell embryos and morulae. There was no sign of maternal effect in the results of reciprocal crosses. PMID- 4029510 TI - Fibrinopeptide-A in diabetes mellitus. Relation to levels of blood glucose, fibrinogen disappearance, and hemodynamic changes. AB - Plasma and urine fibrinopeptide-A (FPA) levels were investigated in type I and II diabetic patients. Plasma FPA and 24-h urinary excretion of FPA were significantly elevated in diabetic patients compared with normal volunteers, indicating augmented thrombin activity in diabetes. Plasma and urine FPA did not differ between type I and type II diabetic subjects. Comparison of plasma FPA with blood glucose and hemoglobin A1 (HbA1) indicated that elevation of FPA is rapidly reversible and intermittent during hypo- and hyperglycemia. Although elevated plasma FPA was seen in patients of short as well as long duration of diabetes, plasma and urine FPA correlated with duration of diabetes in type I patients. In type I diabetic patients with vascular complications, hyperglycemia induced by an oral glucose challenge was accompanied by elevation of plasma FPA and acceleration of fibrinogen disappearance. These responses were not seen when the patients were treated with intravenous (i.v.) heparin before the glucose challenge. In patients without vascular complications, there was also an acceleration of fibrinogen disappearance and a marginal (not statistically significant) elevation of plasma FPA seen after the FPA response observed in vascular disease patients. In all patients, induced hyperglycemia resulted in a decrease in hematocrit and hemoglobin (blood volume expansion) and an increase in pulse pressure indicating hemodynamic changes. The association of hyperglycemia and hemodynamic changes with augmented thrombin activity is consistent with a mechanism for fibrin formation and deposition based on endothelial injury and/or increased vascular permeability. Fibrin deposition due to such a mechanism may participate in the development of the vascular complications of diabetes. PMID- 4029511 TI - Streptozocin-induced diabetes affects rat urinary bladder response to autonomic agents. AB - The response of the urinary bladder body and base to autonomic agents was studied in streptozocin (STZ)-diabetic rats. The bladder body region from 6-wk diabetic rats showed no changes in response to acetylcholine, phenylephrine, or isoproterenol. In contrast, the bladder base region showed a 39% increase in contractile response to acetylcholine and a 37% increased response to phenylephrine. In tissues from 47-wk diabetic animals, the bladder body showed a 51% increased contractile response to acetylcholine and a 37% increased relaxation response to isoproterenol. The bladder base showed a 66% increased contraction to acetylcholine. Thus, in the bladder base, enhanced responses to acetylcholine are detected soon after induction of diabetes and continue to increase as the diabetic state progresses. Moreover, in the same bladder region, an increase in responsiveness to alpha-adrenergic stimuli occurs. In the bladder body, enhanced responses to cholinergic and to beta-adrenergic stimuli occur, but are only observed in a more chronic diabetic state. The data suggest that an effect associated with autonomic diabetic neuropathy of the urinary bladder is an increased postsynaptic responsiveness to cholinergic stimuli in both regions. PMID- 4029512 TI - Nonenzymatic glycosylation products on collagen covalently trap low-density lipoprotein. AB - Advanced nonenzymatic glycosylation products capable of cross-linking proteins accumulate on collagen in vivo in proportion to time-averaged blood glucose concentration. In this report, we have evaluated the ability of advanced nonenzymatic glycosylation products formed on collagen in vitro to covalently bind low-density lipoprotein (LDL) in a manner similar to that which occurs in human atherosclerotic lesions. At constant LDL concentration, covalent trapping increased linearly with the extent of advanced glycosylation product formation, from 1.42 +/- 0.15 to 4.46 +/- 0.36 micrograms LDL protein/mg collagen. At a constant level of collagen advanced glycosylation product, LDL binding increased as a function of increasing LDL concentration. At an LDL-cholesterol level of 103 mg/dl, covalent trapping of LDL by nonenzymatic glycosylation products on collagen averaged 3.2 times as much as control (P less than 0.01). These data indicate that LDL is bound specifically by reactive products generated by nonenzymatic glycosylation of collagen, and suggest that excessive LDL trapping by hyperglycemia-induced advanced glycosylation endproducts may contribute to the accelerated development of atherosclerosis in patients with diabetes mellitus. PMID- 4029513 TI - Policy statement. Self-monitoring of blood glucose. American Diabetes Association. PMID- 4029514 TI - Policy statement. Continuous subcutaneous insulin infusion. American Diabetes Association. PMID- 4029515 TI - Maturation of the visual evoked response and its correlation with visual acuity in preterm infants. AB - Visual evoked responses (VERs) were elicited in 70 infants with postmenstrual ages between 30 and 39 weeks. On the basis of neurological and ultrasound examinations, 30 of the infants were classed as neurologically normal and 40 as abnormal: 26 of the latter had periventricular haemorrhage. Initially the VER consisted of a negative deflection only, and the appearance of a positive wave immediately preceding the negative deflection was taken to indicate maturation of the VER. Maturation was significantly delayed in the neurologically abnormal infants, and the delay was related to the degree of neurological insult. The visual acuity of 32 infants was estimated within seven days of the VER recording. There was a correlation of 79 per cent between the VER and the data for visual acuity. PMID- 4029516 TI - What mothers know about their newborns' visual skills. AB - Fifty-four mothers were asked whether they had observed evidence that their baby could see, whether this was expected, and where they had obtained information about babies. 61 per cent had not expected their baby to see, and 47 per cent did not think their baby could see. These findings were not affected by social class, parity, age of baby, or hospital attended. The most common source of information was reading matter, but mothers were often misinformed and confused. Most had seen their baby smile but there was a tendency among those who did not think their baby could see to attribute this to 'wind' rather than to a social response. 81 per cent of mothers breastfed initially. On follow-up there was a tendency for those who had thought their baby could see at the time of the first interview to maintain breastfeeding beyond the first month and to continue breastfeeding for longer than mothers who had thought that their baby could not see. PMID- 4029517 TI - Term infants with hypoxic-ischemic encephalopathy: outcome at 3.5 years. AB - A total of 167 term neonates with a diagnosis of hypoxic-ischemic encephalopathy (HIE) had detailed neurodevelopmental follow-up at 3.5 years of age. All 66 children with mild HIE were free from handicap; all seven with severe HIE were severely handicapped; and of the 94 with moderate HIE at birth, 21.3 per cent were handicapped. Mean IQ was significantly related to the category of HIE. Within the moderate HIE category, the neurological examination at discharge from the Neonatal Intensive Care Unit was more useful than the presence of neonatal convulsions in identifying children with subsequent developmental delay. Abnormalities on this examination related significantly to an increased number of handicapped children, decreased motor and language skills, and lower IQs. Although neonatal convulsions were associated with an increased number of handicapped children, they did not significantly affect most other developmental outcome measures. In term infants with documented HIE at birth, major neurodevelopmental dysfunction at 3.5 years depended more on prospectively established category of HIE than on other perinatal or social factors. PMID- 4029518 TI - Energy cost index as an estimate of energy expenditure of cerebral-palsied children during assisted ambulation. AB - The energy expenditure of cerebral-palsied children ambulating with bilateral quad canes and wheeled walkers was estimated, using average heart rate and speed of walking. An energy cost index (average number of heart rates per unit distance walked) was derived to allow for varying speeds among patients. Children were then categorized into those who had a lower energy cost index when using quad canes and those who had a lower index when using walkers. This made it possible to offer treatment recommendations based on objective data. PMID- 4029519 TI - Motor overflow and attentional processes in normal school-age children. AB - Two groups of 28 school-age children (divided equally by sex) who were equivalent in terms of chronological age and IQ but differed in the prevalence of motor overflow were given a concept identification task designed to measure relative attentiveness to central, task-related cues and incidental, social environmental ones. Children with a high level of overflow were relatively more responsive to social cues than to task-related ones, while children with a low level were more equally responsive to the two types of cues. The results are interpreted in terms of a relationship between motor overflow and attentional processes. PMID- 4029520 TI - Psychosocial and cultural factors associated with the management of spina bifida cystica in Nigeria. AB - A prospective study of the psychosocial and cultural factors influencing the management of spina bifida cystica was carried out on Nigerian children (48 males, 28 females) seen at the University College Hospital, Ibadan, between January 1982 and December 1983. The parents of 74 of the 76 children had never heard of the disease, many had no idea of its causation and one-third incriminated witchcraft. Of primary concern was the cyst on the back. The better educated parents tended to demand surgical treatment more than the illiterate parents. 22 children were treated surgically. The default rate was high because parents failed to get the expected hospital treatment. Most mothers showed relief rather than remorse on the death of their child. PMID- 4029521 TI - Educational attainment of 10-year-old children with treated and untreated visual defects. AB - Children with visual defects who took part in a 10-year survey were compared with their peers on measures of intelligence, reading, mathematics and sporting ability. Results are consistent with earlier findings of increased intelligence among children with myopia and slightly reduced intelligence among children with amblyopia. Those with other visual defects had normal intelligence scores. Once intelligence had been taken into account, only children with mild hypermetropia were under-achieving at reading. Those with severe myopia were reading better than expected. None of the children could be shown to be over- or under-achieving at maths, any variation being due to intelligence. The mothers of children with visual defects perceived them to be less able at sport. Comparison of the performances of children with minor visual defects who had and had not been prescribed spectacles did not suggest any disadvantage for those without spectacles, with the possible exception of children with mild hypermetropia. It is concluded that the majority of visual defects do not affect children's learning, and that current indications for prescribing spectacles need to be validated. PMID- 4029522 TI - Glutaric aciduria type I misdiagnosed as Leigh's encephalopathy and cerebral palsy. AB - Two cases are reported of boys who suffer epileptic seizures only after playing video games. It is suggested that the amount of time the patient spends in front of the screen before the seizure is important, and also that video games trigger electrocortical activity far more efficiently than either television or intermittent photic stimulation. PMID- 4029523 TI - Treatment of scoliosis in Duchenne muscular dystrophy. PMID- 4029524 TI - Muscle wasting in the muscular dystrophies. PMID- 4029525 TI - Vocal-cord paralysis and brainstem dysfunction in children with spina bifida. PMID- 4029526 TI - The development of the human blood-CSF-brain barrier. PMID- 4029527 TI - Convulsions and lumbar puncture. PMID- 4029528 TI - [Prolactin and obesity: aspects of hypothalamic pathology]. PMID- 4029529 TI - [Pathogenesis of rheumatoid synovitis: critical review]. PMID- 4029530 TI - [Evaluation of citrates in a group of patients with idiopathic calcium calculi]. PMID- 4029531 TI - [The ergometry test in the elderly]. PMID- 4029532 TI - [Glycosylated hemoglobin in chronic renal insufficiency]. PMID- 4029533 TI - [A case of giant neurinoma of the mediastinum]. PMID- 4029534 TI - [Myocardial function in patients with chronic alcoholic liver disease: echocardiographic findings]. PMID- 4029535 TI - The multidisciplinary approach to dysphagia. PMID- 4029536 TI - Anatomy and physiology of the pharynx. AB - Radiographic evaluation of the passage of a bolus from the mouth through the pharynx into the esophagus is based upon identification of specific anatomical landmarks and the integrated motion accomplished by the oral and pharyngeal muscles during swallowing. Twenty-six muscles and 6 cranial nerves must be coordinated to enable the safe performance of the complex physiological task of transporting liquids and firm food from the mouth into the esophagus. The following discussion and illustrations of pharyngeal anatomy and physiology are pertinent to an understanding of normal swallowing function. PMID- 4029537 TI - Dynamic imaging of the pharynx. AB - The technique of dynamic imaging of the pharynx and some supplementary maneuvers which can be tailored to the individual patient's needs are discussed in detail. An approach to the analysis of normal and abnormal swallowing studies is presented. PMID- 4029539 TI - Adaptation, compensation, and decompensation of the pharyngeal swallow. AB - Under normal circumstances, the act of swallowing adjusts to varying demands of different bolus characteristics and different head and neck postures. When the swallowing mechanism is impaired by disease, adjustment is essential to compensate for the impairment and allow swallowing. Evidence of adjustment can be demonstrated by cineradiography which provides important clues to the presence of underlying disease. When adjustment to disease is inadequate, swallowing decompensates. In this case, gross changes in swallowing performance are evident from clinical evaluation and cineradiography. PMID- 4029538 TI - Pharyngoesophageal interrelationships: observations and working concepts. AB - Simultaneous disorders of the pharynx and esophagus are so frequent that the complete swallowing chain should be examined in all patients with dysphagia. Data are presented to support the concept that such simultaneous disorders represent related phenomena; the mechanism involves changes in cricopharyngeal function seen radiographically as cricopharyngeal prominence. If neurologic disease has been excluded, cricopharyngeal prominence may be the clue to esophageal disease. When cricopharyngeal prominence is found during dynamic imaging of the pharynx, intensive examination of the esophagus and a search for signs of compensation or decompensation in the pharynx should be undertaken. PMID- 4029540 TI - Special swallowing problems in children. AB - As the swallowing process evolves from infantile suckle feeding through transitional feeding to mature function, the process can go awry at many points. Understanding the changes in structure and function of the mouth and pharynx that occur with growth and development is of basic importance. When a child is referred because of unsuccessful feeding or suspicion of aspiration, dynamic imaging of the swallowing mechanism and scrutiny of radiographic abnormalities described in this article can lead to greater understanding of the underlying cause and to more effective treatment. PMID- 4029541 TI - Dynamic imaging for swallowing reeducation. AB - Dynamic imaging is frequently indispensable for the rational treatment of disordered swallowing. The effects of test feeding techniques, bolus modification, patient positioning, and respiratory maneuvers are all best documented by visualizing and recording the swallowing of radiopacified boluses. What is seen becomes the basis of patients' reeducation in swallowing. Greatest effectiveness results when the radiologic examination is shared with those responsible for the patient's rehabilitation in swallowing. PMID- 4029542 TI - The Swallowing Center: concepts and procedures. AB - This paper describes the purpose and organization of a dedicated center at The Johns Hopkins Medical Institutions for the evaluation of swallowing problems. The multidisciplinary approach outlined will permit a better understanding and more accurate diagnosis of the functional or organic lesions affecting the swallowing mechanisms. Illustrative cases are presented. PMID- 4029543 TI - Double-contrast examination of the pharynx. AB - The radiographic techniques for evaluation of the pharynx are described, with particular emphasis on double-contrast examination. Radiographic anatomy of the pharynx is illustrated. PMID- 4029544 TI - Upper gastrointestinal series: patient management and a study of 199 cases. AB - Records of 199 patients were analyzed retrospectively after upper gastrointestinal (UGI) series to assess its impact on patient management. Symptoms most predictive of an abnormal UGI series were dysphagia, UGI hemorrhage, abdominal pain, and chest pain. However, 23% of inpatients with seemingly trivial symptoms had shown abnormal results of the study. Overall sensitivity of the UGI series was 65%, which rose to 82% if esophagitis, gastritis, and abnormalities of the postoperative stomach were excluded. Effects on patient management included: serious pathologic change ruled out (53%), further studies ordered (21%), change of therapy (17%), existing therapy continued (16%), surgery performed (7%), and radiologic abnormality ignored (5%). In no case did the combination of initial screening by UGI series followed by endoscopy as indicated lead to subsequently reported morbidity or mortality due to a failure of diagnosis. PMID- 4029545 TI - Secondary involvement of the transverse colon by tumors of the pelvis: spread of malignancies along the greater omentum. AB - Based on selected case studies the pathways of spread of malignancies arising from the pelvis are discussed. Secondary involvement of the transverse colon with characteristic lesions at the inferior border may be seen in these cases, caused by metastatic spread via the greater omentum. Ultrasonography and computed tomography may prove this diagnosis by showing peritoneal metastatic spread and tumorous infiltration of the greater omentum. PMID- 4029546 TI - Computed tomography in complicated acute appendicitis. AB - Due to the position and length of the appendix, intraabdominal abscesses after perforation in complicated acute appendicitis may occur in several different and sometimes unsuspected anatomical locations. Five patients are described with proven complicated acute appendicitis and inflammatory processes in multiple sites: anterior pararenal space, general retroperitoneum, subcutaneous fat space, intraperitoneal cavity, and small bowel mesentery. A confusing case of ileocecal carcinoid with mesenteric involvement is also presented. In all cases complicated acute appendicitis was diagnosed on CT prior to surgery, except in 1 case in which a pelvic abscess developed after intramural cecal bleeding in a patient with hemophilia B. PMID- 4029548 TI - Abstracts of scientific presentations. Society of Gastrointestinal Radiologists' fourteenth annual meeting. Napa, California, September 29-October 3, 1984. PMID- 4029547 TI - Infected calcified mucocele of the appendix with histologic features of mucinous cystadenoma. AB - A case of calcified and infected mucocele of the appendix is reported. The appearance of the calcification, the presence of gas with an air fluid level on plain films, and the opacification of the lumen of the mucocele by opaque enema allowed the correct radiologic diagnosis to be made. PMID- 4029549 TI - Exocrine pancreatic function in asymptomatic chronic alcoholics without structural pancreatic disease. AB - In order to elucidate the functional states of the pancreas in the asymptomatic latent stage of chronic alcoholic pancreatitis, 45 chronic alcoholics with no obvious pancreatic structural abnormalities judged by endoscopic pancreatography were studied by pancreozymin-secretin test. We found three patterns of exocrine pancreatic function in alcoholics with or without cirrhosis: normal secretion (40%), hyposecretion (29%) and hypersecretion (31%). In the hyposecretory group, the amylase output proved to be impaired more frequently. In the hypersecretory group increases were observed in one or more of the following parameters, volume, bicarbonate output and amylase output. However, increase in volume was a fundamental condition in this hypersecretion. This study confirmed that exocrine pancreatic hyposecretion and hypersecretion were almost equally frequent in asymptomatic chronic alcoholics with no obvious pancreatographic abnormalities. These results suggest that ongoing exocrine pancreatic dysfunctions exist in the subclinical stage of chronic alcoholic pancreatitis. PMID- 4029550 TI - Effect of cimetidine on portal pressure and systemic hemodynamics in patients with and without liver cirrhosis. AB - Portal pressure and systemic hemodynamics were evaluated for 30 minutes after intravenous injection of 400 mg of cimetidine in patients with and without liver cirrhosis when they were operated upon for varying surgical diseases. A transient fall of arterial pressure was seen in both groups of patients, but the change was statistically significant only in those with cirrhosis. Cimetidine did not substantially alter pulse rate, CVP, and portal pressure in both groups. The present results seem to indicate that rapid administration of cimetidine does not induce a fall of portal venous pressure in both cirrhotic and non-cirrhotic patients. PMID- 4029551 TI - Improvement of endoscopic and histologic findings of AA-type gastrointestinal amyloidosis by treatment with dimethyl sulfoxide and prednisolone. AB - We report the successful treatment of gastrointestinal amyloidosis with dimethyl sulfoxide. A 37 year-old man with adult-onset Still's disease suffered from diarrhea. Upper and lower gastrointestinal endoscopy revealed edematous mucosa, white patches, erosions and bleeding and amyloid deposits were demonstrated in biopsy specimens. After a period of 3 months dimethyl sulfoxide and prednisolone therapy, improvement in the endoscopic appearance of the gastrointestinal tract was observed. Amyloid deposits in biopsy specimens were reduced in the stomach and negative in the large intestine. PMID- 4029552 TI - Two stage total gastrectomy in a case of multiple bleeding gastric ulcers. AB - A 78-year-old man with severe diabetes mellitus fell into shock due to bleeding from multiple gastric ulcers. Near-total gastrectomy without reconstruction was performed in the initial operation to save his life. After his general condition improved, total gastrectomy with Roux-en-Y esophagojejunostomy was performed in a second procedure. As this two stage total gastrectomy can avoid excessive operative stress, and prevent rebleeding and breakdown at the anastomosis, we consider it a valuable procedure for patients who have multiple bleeding gastric ulcers involving almost the whole stomach, and who have very poor general condition or severe complications at the time of operation. PMID- 4029553 TI - Protection of liver cells from experimentally induced liver cell injury by glycyrrhizin. AB - Liver cell damage is induced when isolated liver cells coated with specific antibody against the liver cell membrane are cultured with peripheral blood mononuclear cells. Although this antibody-dependent cell-mediated cytotoxicity (ADCC) was induced by closed contact of effector cells with targets via specific antibody, a cytotoxic factor or factors causing inhibition of protein synthesis in liver cells was detected in the culture supernatant of the ADCC reaction. Similarly, peritoneal exudate macrophages activated by endotoxin lipopolysaccharide (LPS) also had cytotoxic effects on isolated liver cells by producing a cytotoxic substance or substances. These liver cell injuries caused by either ADCC or activated macrophage culture supernatants were significantly reduced by pretreatment of the isolated liver cells with glycyrrhizin before the addition of the cytotoxic culture supernatants. These results suggest that glycyrrhizin may protect liver cells from immunological injuries. PMID- 4029554 TI - Diadenosine tetraphosphate as a signal molecule linked with the functional state of rat liver. AB - Diadenosine 5',5"'-P1,P4-tetraphosphate (Ap4A), which has been suggested to be a signal nucleotide involved in positive growth regulation, was determined in rat liver under various conditions using the luciferin/luciferase system. The Ap4A level was 920 pmol/g of wet liver in normal adult rats, but was high at early stages of growth, the maximum value being 1460 pmol/g in 3-wk-old rats. An increase in Ap4A levels preceded deoxyribonucleic acid synthesis in liver after hepatectomy. Ap4A levels were increased 5.5-fold (5125 pmol/g) 24 h after hepatectomy. The range of such increases was closely correlated with the mass of liver removed. Cholestasis produced by bile duct ligation and intraperitoneal injection of D-galactosamine remarkably lowered the Ap4A level to 20% and 42%, respectively; however, the adenosine triphosphate level was only slightly decreased to 65% and 78%, respectively. Fourteen days after bile duct ligation, Ap4A levels fell to less than 220 pmol/g, and the rats could no longer survive partial hepatectomy. These results suggest that hepatic Ap4A levels correlate positively with regenerative activity. PMID- 4029555 TI - Hepatic decompensation associated with hepatitis B e antigen clearance in chronic type B hepatitis. AB - To examine hepatic decompensation associated with acute exacerbation preceding hepatitis B e antigen clearance in chronic type B hepatitis, 376 patients with chronic hepatitis who were hepatitis B e antigen-positive were prospectively studied for up to 7 yr (mean 25 mo). Among the 165 patients who underwent hepatitis B e antigen clearance, 4 patients experienced hepatic decompensation and one of them eventually developed hepatic encephalopathy and died. The incidence of hepatic decompensation associated with hepatitis B e antigen clearance was 2.4%. We suggest that such an event in previously unrecognized chronic hepatitis B carriers could have been erroneously interpreted as acute or subacute hepatic failure, and that it might have been the result of a stronger enhancement of the host immune response. PMID- 4029556 TI - Developmental characteristics of the lower esophageal sphincter in the kitten. AB - Gastroesophageal reflux is a common event during infancy. Developmental factors may be responsible for incompetence of the lower esophageal sphincter (LES) in this age group. We used the cat as a model to evaluate in vivo and in vitro the mechanical factors responsible for LES pressure during infancy. We found that in vivo the kitten develops lower LES pressure than the adult cat. For in vitro studies consecutive rings 1.75 mm wide were obtained from the LES region of 3-day , 1-wk-, 3-wk-, and 6-wk-old kittens and of adult animals. Force-length curves were obtained in standard Tyrode's solution, in Tyrode's solution with high KCl, and in calcium-free Tyrode's solution with ethylenediaminetetraacetic acid disodium salt to determine basal, total, and passive forces, respectively. Active force is given by the difference between total and passive force. The maximum active force generated was lowest in the 3-day-old kittens and increased with age, being highest in the adult cat. Stresses, obtained by normalizing forces for the amount of muscle available, were greater in the kitten than the adult. The ratio of muscle thickness to its inner radius is markedly reduced in the kitten. As intraluminal or LES pressure is given by the product of stress and thickness to-radius ratio, this might explain why lower pressures are generated despite the higher stresses developed. PMID- 4029557 TI - Gastric distention: a mechanism for postprandial gastroesophageal reflux. AB - The occurrence of gastroesophageal reflux after meals may be related to an increase in the rate of transient lower esophageal sphincter (LES) relaxations, the mechanisms of which are not understood. We investigated the effects of gastric distention on LES pressure in 16 normal subjects and 17 patients with gastroesophageal reflux disease. Intraluminal pressure was measured in the gastric fundus, LES, and esophageal body with a manometric catheter incorporating a sleeve device. Gastric distention was performed by injecting 0, 250, 500, or 750 ml of air in randomized order into a balloon and maintaining each stimulus for 15 min. Gastric distention did not significantly alter resting LES pressure in either group. During the basal period the rate of transient LES relaxation in the reflux patients (1.1 +/- 0.4 per 15 min) was greater than that in the normal subjects (0.6 +/- 0.1 per 15 min). Gastric distention resulted in a significant threefold to fourfold increase in the rate of transient LES relaxations in both groups. The reflux patients had a significantly greater proportion of complete relaxations (87%) than did the normal subjects (73%). We conclude that gastric distention, by significantly increasing the rate of transient LES relaxations in both normal subjects and patients with gastroesophageal reflux disease, may contribute to the postprandial increase in gastroesophageal reflux. PMID- 4029558 TI - Effect of fat and carbohydrate composition on the gastric emptying of isocaloric feedings in premature infants. AB - The gastric emptying of six infant feedings (20 kcal/oz; whey to casein ratio, 60:40) with varying fat and carbohydrate composition was studied. Feedings contained either predominantly long-chain triglycerides (94%) or predominantly medium-chain triglycerides (94%) as the fat and lactose, glucose, or glucose polymers (Polycose) as the carbohydrate. Eleven premature infants were fed 22 ml/kg body wt of all six feedings over a 3-4-day period, and the volume of gastric contents was measured every 20 min using polyethylene glycol 4000 as the marker. Analysis of variance demonstrated that the use of medium-chain triglycerides resulted in faster gastric emptying than long-chain triglycerides (p less than 0.001). Analysis of variance and Tukey's test showed that use of glucose polymers instead of glucose resulted in less volume of gastric contents at 40 min (p less than 0.05). Use of glucose polymers instead of lactose resulted in less volume of gastric contents at 60 and 80 min (p less than 0.05). Gastric emptying can be altered by changes in nutrient composition. The difference between medium-chain and long-chain triglycerides was more pronounced than the differences between the carbohydrates studied. Feedings with medium-chain triglycerides may be more suitable than long-chain triglycerides in patients with delayed gastric emptying. PMID- 4029559 TI - Limitations of 24-hour intraesophageal pH monitoring in the hospital setting. AB - Prolonged intraesophageal pH monitoring is considered by some to be the most sensitive and specific test of gastroesophageal reflux. We prospectively examined the ability of the test to discriminate 64 hospitalized patients with typical reflux symptoms from 20 age-matched hospitalized control subjects. Patients were subdivided based on endoscopic findings into two groups: group 1, normal endoscopy (n = 30); group 2, erosive esophagitis (n = 34). Six different individual reflux variables and a scoring system were evaluated. Total esophageal acid exposure time and the number of reflux episodes requiring longer than 5 min to clear were each found to have greater discriminatory power than other variables and the scoring system. Although the 64 patients had significantly more acid reflux than controls, only 48% had abnormal results (defined as 2 SD from the control mean). Group 1 patients had significantly more reflux than controls, though only 21% had abnormal results. Group 2 patients were significantly different than both controls and group 1, but 29% had normal studies. Ninety three percent of the group 1 patients with normal studies responded to antireflux therapy, and only 1 patient had another explanation for the symptoms. The finding that 24-h pH monitoring was normal in half of the individuals presenting with reflux symptoms and in 29% of the patients with erosive esophagitis indicates that negative test results must be interpreted with caution. The insensitivity of the test may relate to the manner in which the study has traditionally been performed in the hospital, and outpatient ambulatory monitoring may improve its reliability. PMID- 4029560 TI - Effect of size and density on canine gastric emptying of nondigestible solids. AB - Previous studies suggested that the food-containing canine stomach retains large, nondigestible spheres until all food has emptied; but it is not known whether there is a threshold size or a gradation of sizes that will empty along with food. Further, nothing is known of the effects of such parameters as density, shape, and surface energy on the emptying of nondigestible particles of any given size. To answer these questions 6 dogs with chronic duodenal fistulas were studied. Radiolabeled food and spheres were collected from the fistulas to compare the rate of gastric emptying of the spheres with that of the food. After a standard test meal of 99mTc-labeled liver, steak, and water, diverted chyme was collected over a stack of sieves in 30-min fractions over 5 postcibal hours. The percent of fed spheres and fed 99mTc-labeled liver in each collection was counted, and liquid chyme was returned to the distal duodenum. Spheres with a density of 1 emptied progressively faster as sphere diameters were decreased from 5 to 1 mm; but 0.015-mm spheres emptied at about the same rate as those with diameters of 1 mm. Emptying of the spheres became similar to emptying of the 99mTc-labeled liver at about 1.6 mm. Spheres with densities less than 1 or greater than 1 emptied more slowly than spheres of the same size with a density of 1, whereas paper squares emptied the same way as spheres of comparable size and density. Surface energy did not affect emptying. The findings indicated that both sphere size and density affect their emptying in the presence of food. PMID- 4029562 TI - A continuous manometric study of the human pylorus. AB - Previous manometric studies of the pylorus in humans have yielded conflicting data. These interstudy variations may be the result of differences in technique. It is also possible that pyloric pressure shows cyclic variations with the interdigestive motility complex. Pyloric pressure was monitored continuously for 300 min in 6 healthy men by means of a Dent sleeve. Gastroduodenal activity was measured simultaneously by using a perfused catheter system with two antral and two duodenal ports. With this method the pylorus was shown to have no elevation in basal pressure above baseline duodenal pressure during phase III. Basal pyloric pressure varied between subjects in phases I and II, being elevated in some but not in others. Subjects restudied on a separate day often showed a different pattern of activity. Pyloric pressure increased gradually in response to duodenal acidification. This response was blocked by pretreatment with naloxone. The pylorus also showed phasic activity, which was maximal in phase III. This phasic activity could not be distinguished from that of the adjacent antrum and duodenum. In conclusion, pyloric pressure patterns showed marked variation within and between subjects. These variations may explain some of the differences between previous studies. PMID- 4029561 TI - Depression of serum calcium by increased plasma free fatty acids in the rat: a mechanism for hypocalcemia in acute pancreatitis. AB - Some patients with hypertriglyceridemia and acute pancreatitis have marked hypocalcemia and high levels of plasma free fatty acids (FFAs). This study tests the hypothesis that increased plasma FFAs can significantly reduce the calcium level in vivo, a phenomenon which is different from local formation of calcium soaps due to lipolysis of adipose tissue lipids. Free fatty acid elevation was induced in rats by the administration of heparin and by the infusion of triglycerides. The results show that, compared with controls, induction of elevated FFA (from 1.57 +/- 0.08 mEq/L to 5.64 +/- 0.35, mean +/- SEM) causes the concentration of calcium to fall rapidly (from 9.04 +/- 0.06 mg/dl to 8.42 +/- 0.10, p less than 0.001). There is a significant (p less than 0.001) positive correlation between spontaneous baseline concentration of FFA and the responsiveness of calcium concentration to FFA challenge. At near-normal levels of FFA there is a significant (p less than 0.001) correlation between the magnitude of increased FFA concentration and decreased calcium concentration. Additional studies in vivo and in vitro show that elevated plasma triglycerides per se did not interfere with measurement of calcium concentration; however, FFA albumin complexes bind calcium and lower its measured value. These findings suggest that (a) changes in the concentration of FFA occurring spontaneously may affect measured serum calcium concentration; (b) the observed depression of serum calcium concentration may be due in part to intravascular sequestration of calcium by FFA, but increased flux of circulating calcium-FFA complexes into extravascular and intracellular sites may also be important; (c) the markedly increased FFA concentration in some patients with acute pancreatitis may contribute significantly to hypocalcemia and calcium flux in these patients. As parathyroid hormone secretion, function, or integrity may be impaired in pancreatitis, the depressant effect of FFA could be even greater in that disease than in this model. PMID- 4029563 TI - Villous adenomas of the rectum. Results of endoscopic treatment with argon and Nd:YAG lasers. AB - Endoscopic treatment of rectal villous adenomas with argon and neodymium:yttrium aluminum garnet lasers is reported in 56 patients. Patients treated include 25 who had polyp recurrence after non-laser polyp treatment, 8 who had small sessile polyps that would otherwise require major surgery, and 23 who had contraindications to surgery. Complete tumor ablation was documented over a 3-24 mo follow-up period in 42 of the 56 treated patients. Of the remaining 14 patients, 5 were referred for other therapy because invasive carcinoma developed during treatment, 5 could not be assessed with confidence because of radiation proctitis, and 4 were lost to follow-up. In all patients with symptoms, improvement was noted when 75% of the tumor was destroyed. Treatment was well tolerated with no major complications. The results compare favorably with conventional treatment. Because laser tissue destruction precludes complete histologic evaluation of polyp tissue, laser ablation of polyps should presently be limited to (a) patients with recurrent tumors after previous non-laser treatment who refuse surgery, (b) patients with serious contraindications to surgery, and (c) small benign tumors that would require major surgery. PMID- 4029564 TI - Cryptosporidiosis associated with traveling and giardiasis. AB - The aim of this study was to reveal sources where cryptosporidiosis may be acquired. We studied 4545 patients, from whom 5730 stool samples were obtained for the diagnosis of parasitic infections during 13 mo, and found that 119 of these patients (2.62%) excreted oocysts of Cryptosporidium. About two-thirds of the patients reported no animal contacts. There were no cases among children under the age of 5 yr, which is evidence against endemicity, and the prevalence was highest (6.22%) in young adults aged 15-29 yr. The sex distribution was unremarkable: of the 119 patients, 56 were men and 63 were women. Most patients reported a recent trip abroad, which had taken place 12 times more frequently during the previous month than earlier. Cryptosporidiosis was five times more frequent in patients who had recently visited Leningrad than in others, and seven times more frequent in patients with Giardia lamblia than in others. Sporadic cryptosporidiosis occurs mainly in travelers, and seems to be acquired from similar sources as giardiasis. PMID- 4029565 TI - Regional gradient of initial inhibition and refractoriness in esophageal smooth muscle. AB - The influence of two successive vagal stimuli on esophageal contractions was studied by recording intraluminal pressures in the smooth muscle portion of the opossum esophagus. The esophageal contraction in response to the first or second stimulus in a pair of vagal stimuli was inhibited depending on the interstimulus interval, the frequency of the stimulus, and the esophageal site. The esophageal contraction in response to the first vagal stimulus was inhibited by a second vagal stimulus if the latter stimulus was applied before the peak of the first contraction. This phenomenon is termed initial inhibition. Initial inhibition is a graded phenomenon. It was greater at higher frequencies than at lower frequencies (p less than 0.001), and was significantly greater in the distal esophagus than in the proximal esophagus (p less than 0.01). The term "refractoriness" has been used to denote inhibition of the second esophageal contraction by the first. Refractoriness was observed during and beyond the duration of the first esophageal response. Refractoriness was also observed at all esophageal levels; however, the interstimulus intervals that demonstrated refractoriness were significantly greater in the distal than in the proximal esophagus (p less than 0.01). Refractoriness was complete (effective refractory period) during the ascending phase of the first contraction. Refractoriness was incomplete after the peak of the contraction (relative refractory period). These studies show gradients of durations and degrees of initial inhibition and refractoriness along the esophagus. The gradient is responsible for the peristaltic nature of esophageal contraction. The gradients of initial inhibition and refractoriness determine esophageal response to multiple successive swallows. PMID- 4029566 TI - Relationship of blood flow and oxygen consumption to ischemic injury in the canine small intestine. AB - The relationship of blood flow and oxygen uptake to ischemic intestinal injury was investigated by measuring the clearance of 131I-albumin from the blood to the lumen of isolated, perfused segments of canine jejunum. Reductions in blood flow for 2 h to various levels confirmed the previously demonstrated relationship of oxygen uptake to blood flow, i.e., oxygen uptake was flow-independent at blood flows above 30 ml/min X 100 g, and flow-dependent at levels below this. Blood flows above this threshold did not change the level of albumin clearance seen under control conditions (0.022 +/- 0.003 ml/min X 100 g). However, increases in the mucosal permeability to albumin were seen after blood flow was reduced to levels where oxygen uptake was decreased by more than 50%. These findings indicate that the ability of the small intestine to maintain oxygen consumption during low flow states may be an important factor in providing protection from ischemic injury, even during prolonged periods of hypoperfusion. PMID- 4029567 TI - Intestinal pseudoobstruction caused by diffuse lymphoid infiltration of the small intestine. AB - Four young women presented with diarrhea, malabsorption, and intestinal pseudoobstruction. Intestinal biopsy specimens (both peroral and full-thickness) showed flat small intestinal mucosa, sparsity of crypts, and a widespread lymphoid infiltrate in the lamina propria, muscularis propria, and myenteric plexus. There was no neuron or nerve fiber loss or damage in the plexus; muscle cell absence in the vicinity of lymphoid cell infiltration in the muscularis propria probably accounted for the pathogenesis of pseudoobstruction. Immunochemical stains showed that the infiltrate was polyclonal, and none of the patients has developed lymphoma on clinical follow-up of 4-16 yr. Transient improvement in symptoms occurred after antibiotic therapy in 3 patients, and 1 patient had improvement after treatment with cyclophosphamide and prednisone; however, symptoms of pseudoobstruction persist in all. These cases illustrate yet another cause of intestinal pseudoobstruction which is histologically distinct from visceral myopathies and neuropathies. The pathogenesis of this illness may be related to that of diffuse immunoproliferative diseases seen in Third World countries. PMID- 4029568 TI - Peculiar purine nucleotides and liver regeneration. PMID- 4029569 TI - Yersinia enterocolitica peritonitis. PMID- 4029570 TI - Classification of pancreatitis--Cambridge and Marseille. PMID- 4029571 TI - The relationship of bacteremia to the length of injection needle in endoscopic variceal sclerotherapy. AB - The authors evaluated whether depth of needle insertion as determined by needle length is an important factor in sclerotherapy-associated bacteremia. In 18 consecutive sclerotherapy sessions in which sodium morrhuate was used, blood cultures were positive in 11% when using an injector with only 3 to 4 mm of needle protruding beyond the sheath, compared with the 39% incidence of bacteremia previously observed when an injector was used which permitted 6 to 8 mm of needle to protrude (0.01 less than p less than 0.05). Twenty-five additional sclerotherapy sessions in which the shorter needle was used were performed with a different sclerosant, 1% sodium tetradecyl sulfate; only 8% of blood cultures were positive. No correlation was found between fever and bacteremia. The authors conclude that the exposed needle length of the injector must be specified in any report of endoscopic variceal sclerotherapy with the flexible endoscope since this length is critical in the incidence of associated bacteremia and possibly other complications. PMID- 4029572 TI - Incidence of bacteremia with elective upper gastrointestinal endoscopic laser therapy. AB - The incidence of bacteremia associated with endoscopy varies widely for different endoscopic procedures. This study prospectively evaluates the incidence of bacteremia in patients undergoing elective endoscopic laser therapy for two diseases of the upper gastrointestinal tract. In five patients (eight treatment sessions) with arteriovenous malformations, no bacteremia developed. In 15 patients (26 treatment sessions) with esophagogastric carcinoma, bacteremia developed at some time during the procedure in six (40%). However, bacteremia appeared to be associated with the endoscopic insertion through the tumor rather than the laser treatment per se. These findings lead us to conclude that for patients undergoing endoscopy and laser therapy for esophagogastric malignancy, but not for those being treated for arteriovenous malformations, antibiotic prophylaxis to prevent endocarditis may be indicated. PMID- 4029573 TI - Angiodysplasia of the stomach and duodenum. AB - Twenty-five angiodysplasias in the stomach and duodenum were identified with endoscopy in 12 patients. The average age of the patients was 70 years. Two patients had aortic stenosis. Six of the patients were treated with electrocoagulation, three of whom required surgery. Angiodysplasia of the upper gastrointestinal tract is considered to be more common than previously thought and an important cause of both obscure and overt bleeding. PMID- 4029574 TI - Endoscopic appearance of gastric myeloma. PMID- 4029575 TI - Bacterial endocarditis after Hurst bougienage in a patient with a benign esophageal stricture and mitral valve prolapse. PMID- 4029577 TI - Evaluation of the larynx, hypopharynx, and nasopharynx at the time of diagnostic upper gastrointestinal endoscopy. PMID- 4029576 TI - Carcinoid tumors of the duodenum: endoscopic diagnosis of two cases. PMID- 4029578 TI - Mucosal clipping--utility and safety testing in the colon. PMID- 4029579 TI - Treatment of a biliocutaneous fistula by endoscopic insertion of a nasobiliary tube. PMID- 4029580 TI - Who should have endocarditis prophylaxis for upper gastrointestinal procedures? PMID- 4029581 TI - Ulcerative esophagitis in Behcet's syndrome. PMID- 4029582 TI - Peptic ulcer and hyperplastic polyps in chronic gastric volvulus. PMID- 4029583 TI - Medication washout. PMID- 4029584 TI - Gastric rupture due to external cardiac massage following gastroscopy. PMID- 4029585 TI - ERCP and allergic reactions to iodized contrast media. PMID- 4029587 TI - [Drug sensitivity testing of gynecologic tumors using Volm's test and stem cell assay]. AB - A variety of test systems have been developed for predicting the efficacy of cytotoxic drugs in the treatment of individual malignant human tumors. The present paper reports on the author's experience with Volm's short-term chemosensitivity test and Hamburger and Salmon's stem-cell assay. In the Volm test the influence of adriamycin on the incorporation of radioactively labelled uridine in an individual tumor cell suspension was investigated. Comparison with a cytostatic-free control permitted conclusions to be drawn with regard to the proliferation-related chemosensitivity. The stem-cell assay is based on the capacity of certain tumor cells, the so-called stem cells, to form colonies in a bilaminar soft agar system. The growth of the colony of pre-incubated cytostatics was evaluated in relation to that of untreated tumor cells. The Volm test was successful in 63 (95%) out of a total of 66 tests conducted. Twelve tumors were chemosensitive in the test and 51 chemoresistant. In the stem-cell assay, growth of a colony which permitted chemosensitivity to be tested was only found in 27 out of 183 tests. The criterion of chemosensitivity with a reduction of at least 50% in the number of cells in the colony by at least one cytostatic was satisfied by 14 (29%) of the 49 stem-cell assays which could be evaluated, there being no differences between breast and ovarian carcinomas. The two test systems indicated the chemosensitivity correctly in less than 50% of 49 retrospectively evaluated courses of disease. In contrast, resistance was predicted correctly in 90%.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4029586 TI - [Rate of pregnancy in the treatment of sterility during spontaneous and therapy cycles]. AB - Serum hCG was determined in 231 infertility patients in the late luteal phase of spontaneous and therapeutic cycles. The aim was to establish whether the discrepancy between the high number of induced ovulation cycles and the far lower cycle-related pregnancy rate can be explained by subclinical abortion. In 16.7% of spontaneous cycles hCG was positive; in 16.8% of these cases clinical pregnancy subsequently occurred. The rate of biochemically detectable pregnancies was no higher under endocrine therapy. However, under treatment with clomiphene, epimestrol, prolactin inhibitors and glucocorticoids the rate of clinical pregnancies was almost twice as high, and after hMG/hCG therapy clinically demonstrable pregnancies developed from biochemically identified ones in 76% of the cycles. The investigations show that a stimulation therapy leading to ovulatory cycles after multifollicular development increases the clinical pregnancy rate without resulting in a higher rate of very early abortions. PMID- 4029588 TI - [Secondary vulvectomy treatment results in local recurrence of a vulvar carcinoma following electron irradiation]. AB - Between 1965 and 1979 vulvectomy was performed in 41 patients because of histologically demonstrated local recurrence of a vulval carcinoma after electron beam therapy. Of the patients thus treated, 36.6% survived more than 3 years and 19.5% more than 5 years. An analysis of this group of patients shows that only recurrences less than 3 cm in size have a good prognosis with secondary vulvectomy. However, even with a more severe local condition, a secondary vulvectomy is justified as a palliative. Previous electron beam therapy does not represent an absolute contraindication to surgery, even though there may only be secondary healing in almost all cases. PMID- 4029589 TI - [Chronic paroxysmal hemicrania as a postpartum headache syndrome]. PMID- 4029590 TI - Kinetics of passive transport in water/membrane/water system. A mathematical description. PMID- 4029591 TI - Activation of mitochondrial glycerol 3-phosphate dehydrogenase by cadmium ions. AB - Mitochondrial glycerol 3-phosphate dehydrogenase (EC 1.1.2.1.) requires Ca2+ ions for its activity. Cadmium ions also have activatory effect on the enzyme. They activate the glycerol 3-phosphate dehydrogenase in a very narrow concentration range (1-2 mmol/l). As contrasted with calcium, strong inhibitory effect occurred at higher concentrations (3-4 mmol/l). The inhibition induced by cadmium ions was completely reversible by washing of the mitochondria. PMID- 4029592 TI - Thyroid morphological and functional heterogeneity: impact on iodine secretion. AB - Thyroid iodine turnover heterogeneity includes morphological (cellular and colloidal distribution space for iodide) and functional heterogeneity (hormone synthesis in the colloid). In 'normal' rats, both iodide actively trapped by the epithelial cell and that coming from deiodination of iodotyrosines present the same probability for thyroglobulin (Tg) iodination (Tg iodination flux: 4.0 +/- 0.3 micrograms I/day). A portion of the thyroid iodide is sequestered in the colloid lumen and is inoperative in the Tg iodination mechanisms. The masses of cell and colloid compartments are equivalent (0.018 +/- 0.002 micrograms I) while colloid iodide concentration is twice that of the cell (0.11 and 0.06, respectively). The turnover of about 3 micrograms I of colloid iodine (Tg) is follicle diameter-dependent (inter-follicular heterogeneity) and it is mainly characterized by 2 different half lives of 8 and 16 hours, respectively. Ninety percent of the thyroid iodine (hormone) secretion (1.10 +/- 0.11 micrograms I/day) is provided by this compartment rich in iodotyrosine residues (70%). The remaining 10% of iodine secretion is provided by a Tg pool (7 micrograms I) characterized by 2 compartments (intra-follicular heterogeneity) with slow and very slow turnovers. The longer the transit time of Tg molecules in the colloid, the higher their iodothyronine content. PMID- 4029593 TI - The effect of 3H-thymidine on the proliferation of in vitro cultured mammalian cells. AB - The effect of 3H-thymidine on the proliferation of Chinese hamster cells (clone V79) was studied. Following 3H-thymidine application the proliferation of cells (studied on the basis of plating efficiency) was found to be diminished, the drop being dependent on radioactivity (2-20 kBq/ml cultivation medium), the time of application (2-20 h) and specific activity of 3H-thymidine added. Exogenous macromolecular DNA was able to repair, to an important degree the radiotoxic effect of 3H-thymidine on V79 cells by a mechanism other than the mere reduction of specific activity of 3H-thymidine. PMID- 4029594 TI - Temperature-dependent properties of delayed outward current channels in somatic membrane of snail neurones. PMID- 4029595 TI - A contribution to the morphological study of acute changes in the blood vessels of the central nervous system of rats following irradiation with high-energy (4 GeV/nucleon) helium ions. AB - Rats were irradiated with helium ions (4 GeV/nucleon; 2 or 4 Gy). After 4-9 hours or three days, a perfusion was performed and sections of the cerebral cortex were investigated under light and electron microscopes. Changes observed in the vessels of the telencephalic cortex are described. Most of the vessels in the sections analysed showed no signs of damage. In some cases there was a dilated perivascular space; a comparison of its occurrence in irradiated and control animals showed a statistically significant increase in frequency of the phenomenon at a shorter interval after irradiation with a larger dose. Electron microscopical analysis showed that the main locality of damage was the border of the perivascular foot of the astrocytes, which exhibited various degrees of edema. The discussion stresses the peculiarities of the interaction of helium ions with living tissues, particularly the heterogeneity of the distribution of absorbed energy. The consequence is in accordance with the nature of the changes observed. PMID- 4029596 TI - Nucleotide sequence-dependent opening of double-stranded DNA at an electrically charged surface. AB - It has been shown earlier that the DNA double helix is opened due to a prolonged contact of the DNA molecule with the surface of the mercury electrode. At neutral pH, the opening process is relatively slow (around 100 s), and it is limited to potentials close to -1.2 V (against SCE). The opening of the double helix has been explained by strains in the DNA molecule due to strong repulsion of the negatively charged phosphate residues from the electrode surface where the polynucleotide chain is anchored via hydrophobic bases. Interaction of the synthetic ds polynucleotides with alternating nucleotide sequences/poly(dA dT).poly (dA-dT), poly (dA-dU).poly (dA-dU), poly (dG-dC).poly (dG-dC)/ and homopolymer pairs/poly (dA).poly (dT), poly (rA).poly (rU) and poly (dG).poly (dC)/ with the hanging mercury drop electrode has been studied. Changes in reducibility of the polynucleotides were exploited to indicate opening of the double helix. A marked difference in the behaviour was observed between polynucleotides with alternating nucleotide sequence and homopolymer pairs: opening of the double-helical structures of the former polynucleotides occurs at a very narrow potential range (less than 100 mV) (region U), while with the homopolymer pairs containing A X T or A X U pairs, the width of this region is comparable to that of natural DNA (greater than 200 mV). In contrast to natural DNA, the region U of homopolymer pairs is composed of two distinct phases. No region U was observed with poly (dG).poly (dC). In polynucleotides with alternating nucleotide sequence, the rate of opening of the double helix is strongly dependent on the electrode potential in region U, while in homopolymer pairs, this rate is less potential-dependent. It has been assumed that the difference in the behaviour between homopolymer pairs and polynucleotides with alternating nucleotide sequence is due to differences in absorbability of the two polynucleotide chains in the molecule of a homopolymer pair (resulting from different absorbability of purine and pyrimidine bases) in contrast to equal adsorbability of both chains in a polynucleotide molecule with alternating nucleotide sequence. It has been shown that the mercury electrode is a good model of biological surfaces (e.g. membranes), and that the nucleotide sequence dependent opening (unwinding) of the DNA double helix at electrically charged surfaces may play an important role in many biological processes. PMID- 4029597 TI - Emission of microvesicles and erythrocytic spherocytation. AB - We have examined mathematically the "cause-effect" relationship between the phenomenon of emission of microvesicles and that of erythrocytic sphericitation, especially when the age of the cell is the main factor involved. PMID- 4029598 TI - Membrane digestion and transport under physiological conditions: a review of available data. AB - A technique to study membrane digestion and transport in the small intestine under physiological conditions has been developed. The technique is based on a continuous perfusion of a chronically isolated loop of the rat small intestine. Membrane hydrolysis and transport of some nutrients in the rat small intestine in chronic, as well as in acute (in situ) experiments was investigated. The absorption of hexoses and amino acids has been found to be 2.5-4 times higher under physiological conditions than in acute in situ experiments. Both the active transport of glucose released from maltose hydrolysis and the hydrolysis of the latter is increased under physiological conditions. A coupling between the final stages of hydrolysis and the initial stages of transport in chronic experiments was shown to be highly efficient; practically all or nearly all glucose released is being transported without entering the luminal phase. The hydrolysis rate of starch during the perfusion of a small intestinal segment in chronic experiments is many times higher than that in acute experiments or under anaesthesia. The enzymatic and transport activities revealed using a widely accepted technique in situ, the more so, in vitro account for only a small fraction of those which are typical of undisturbed processes under conditions close to the physiological. The levels of functioning of the digestive-transport systems of the small intestine considered as natural levels developed in the process of evolution, actually reflect only residual processes and, in most cases, they account for 1/3 to 1/10 of the true level of an actual physiological process. PMID- 4029599 TI - Principal component analysis for a better understanding of the herbicidal effectivity of some benzonitriles. AB - To gain more insight in mode of action of ten different 4-hydroxy-benzonitrile derivatives, their biological activities in eight bioassays, and their lipophilicity and adsorptivity determined by thin-layer chromatography in nine different systems were subjected to principal component analysis. Four background components explained about 90% of total variance. Only three of eight biological activities, the inhibition of the 2,6-dichlorophenol-indophenol reduction by spinach and wheat chloroplasts and the CO2 fixation of wheat seedlings had not any common background components with the physico-chemical parameters of the compounds. The nonlinear mapping of principal component loadings and variables showed, that the in vivo and in vitro biological activities differed considerably and depended on the object investigated. The effectivity of compounds is governed mainly by the number of substituents and by the presence of free hydroxy group. PMID- 4029600 TI - Mechanical response of bilayer lipid membranes during bacteriorhodopsin conformation changes. PMID- 4029601 TI - Effect of slow calcium channel blockers on the electromechanical activity of frog myocardium in the presence of epinephrine. AB - The calcium channels blockers fenihidine (3.5 X 10(-5) mol/l), ryosidine (10(-5) mol/l), D-600 (10(-5) mol/l) and Mn ions (2 X 10(-3) mol/l or 5 X 10(-3) mol/l) block contraction force and shorten the duration of action potentials of the frog myocardial ventricle strand under normal conditions. When contraction force and the duration of action potentials were restored by epinephrine (10(-5) mol/l), these agents were unable to suppress these parameters. The increase in both contraction force and the duration of action potentials induced by epinephrine were blocked by acetylcholine. Recording by voltage clamp of inward calcium current (Ica) of the frog atrial trabeculae it was found that fenihidine decreases Ica activated by epinephrine to a smaller extent than observed at normal conditions. Let as assume that epinephrine increases Ica by means of increasing number of calcium channels so these data support the proposed existence of as many as two calcium channel fractions in frog myocardium, which differ in the sensitivity to calcium channels blockers. PMID- 4029602 TI - Sodium transport and electrical properties of the chick chorioallantoic membrane. AB - Transport and electrical properties of the chick chorioallantoic membrane (CAM) were studied in order to find the osmoregulatory organ which helps to compensate the renal filtration-reabsorption disbalance of chick embryos. It could be shown that CAM resembles Na+ transporting epithelia in that active Na+ absorption is responsible for the potential difference and short circuit current, which could be abolished by ouabain on the ectodermal and amiloride on the endodermal side. The transepithelial conductance rose with increasing sodium concentration in accordance with the Michaelis-Menten kinetics. The allantoic sac thus plays a role similar to the toad urinary bladder despite the low potential difference and resistance which indicate that CAM is a leaky epithelium. CAM is therefore not only a respiratory but also an osmoregulatory organ. PMID- 4029603 TI - The influence of certain colchicine derivatives on the growth characteristics of L cells. AB - Colchicine and its derivatives (demecolcine, 2-demethyldemecolcine and acetylated 2-demethyldemecolcine) blocked the mitotic activity of L cells and inhibited proliferation and DNA synthesis. This effect depended on the length of the exposure and the concentration of the substances tested (from 0.05 micrograms/ml up to 2.6 micrograms/ml). The greatest values of plating efficiency, cell proliferation, mitotic index and inhibition of DNA synthesis, respectively, were found after the application of colchiciline (0.2 micrograms/ml). These effects were reversible, since L cells underwent regeneration of the mitotic spindle and renewal of their function after the removal of colchiciline. Reversible effects were much less with other colchicine derivatives tested. The different effects of colchicine and its derivatives were due to their chemical structure, which determines the interactions with respective L cell receptors and thus modifies the mechanism of action on the mitotic apparatus of L cells. PMID- 4029604 TI - Voltammetry of tobacco mosaic virus and its isolated protein at the graphite electrode. AB - The electrochemical behaviour of tobacco mosaic virus (TMV) and its isolated protein was studied using differential pulse (DP) voltammetry at a graphite electrode and by direct current (DC) polarography in Brdicka solution. TMV and its isolated protein were found to be electrooxidized at the graphite electrode in the adsorbed state. Both species yielded two oxidation peaks on DP voltammograms. The first, more negative peak, corresponded to electrooxidation of tyrosine residues, whereas the other, more positive, peak corresponded to electrooxidation of tryptophan residues. DC polarography was used to detect degradation of TMV and denaturation of TMV-protein induced by an increased pH and by the addition of urea, respectively. These structural transformations resulted in increased DP voltammetric oxidation currents as recorded using a graphite working electrode. It has been suggested that the higher oxidation currents were due to an increase in the number of tyrosine and tryptophan residues accessible to the reaction at the graphite electrode. The results of these electrochemical investigations were in a good agreement with the estimation of the accessibility of tyrosine and tryptophan residues based on the well-explored three-dimensional structure of TMV and its isolated protein. PMID- 4029605 TI - Superprecipitation of hybrid actomyosin containing pathologic actin from failing hearts of adults and infants. AB - Superprecipitation (SP) of artificial actomyosin, obtained by hybridization of Straub actin from the human myocardium with myosin of normal animal hearts was studied. Actin was prepared from the myocardium of persons who died of congestive heart failure and various non-cardiac diseases, as well as of infants whose death resulted from toxic pneumonia complicated or not with heart failure. It was shown that, in the control hybrid actomyosin, the substitution of normal Straub actin by that from the failing heart resulted in decrease of both the rate and extent of SP. The conclusion was made that both changes in myosin properties and Straub actin underlie the reduced contractility of the myofibrillar protein system in acute and congestive heart failure. PMID- 4029606 TI - Pharmacokinetics of ethimizol in healthy and gamma- irradiated rats. PMID- 4029607 TI - Localized conversion in Streptococcus pneumoniae recombination: heteroduplex preference. AB - In pneumococcal transformation the frequency of recombinants between point mutations is generally proportional to distance. We have recently described an aberrant marker in the amiA locus that appeared to enhance recombination frequency when crossed with any other allele of this gene. The hyperrecombination that we have observed in two-point crosses could be explained by two hypotheses: the aberrant marker induces frequent crossovers in its vicinity or the mutant is converted to wild type. In this report we present evidence showing that, in suitable three-point crosses, this hyperrecombination does not modify the recombination frequency between outside markers, suggesting that a conversion occurs at the site of this mutation. To estimate the length over which this event occurs, we isolated very closely linked markers and used them in two-point crosses. It appears that the conversion system removes only a few base pairs (from three to 27) around the aberrant marker. This conversion process is quite different from the mismatch-repair system controlled by hex genes in pneumococcus, which involves several thousand base pairs. Moreover, we have constructed artificial heteroduplexes using separated DNA strands. It appears that only one of the two heteroduplexes is specifically converted. The conversion system acts upon 5'..ATTAAT..3'/3'.. TAAGTA..5'. A possible role of the palindrome resulting from the mutation is discussed. PMID- 4029608 TI - Fine structure and instability of the Ml-a locus in barley. AB - There are many naturally occurring variants at the Ml-a locus in barley that confer resistance to the powdery mildew fungus Erysiphe graminis f. sp. hordei. Since the Ml-a locus is bracketed by Hor-1 and Hor-2, genes that encode storage proteins in the endosperm, the Ml-a locus is amenable to fine structure analysis. Rare susceptible recombinants, as judged by exchange of flanking markers, were recovered in F3 families from the Ml-a10 X Ml-a1, Ml-a1 X Ml-a15 and Ml-a6 X Ml a13 crosses. Some susceptible recombinants were recovered from the Ml-a6 X Ml-a13 cross that did not fit the expected F3 family segregation ratios. The Ml-a6/Ml a13 recombinants often reverted to resistance in subsequent generations. No recombinants were recovered in the reciprocal cross, Ml-a13 X Ml-a6. The possibility of a transposable element and a possible linear order of six "alleles" at the Ml-a locus is discussed. PMID- 4029609 TI - Statistical properties of the number of recombination events in the history of a sample of DNA sequences. AB - Some statistical properties of samples of DNA sequences are studied under an infinite-site neutral model with recombination. The two quantities of interest are R, the number of recombination events in the history of a sample of sequences, and RM, the number of recombination events that can be parsimoniously inferred from a sample of sequences. Formulas are derived for the mean and variance of R. In contrast to R, RM can be determined from the sample. Since no formulas are known for the mean and variance of RM, they are estimated with Monte Carlo simulations. It is found that RM is often much less than R, therefore, the number of recombination events may be greatly under-estimated in a parsimonious reconstruction of the history of a sample. The statistic RM can be used to estimate the product of the recombination rate and the population size or, if the recombination rate is known, to estimate the population size. To illustrate this, DNA sequences from the Adh region of Drosophila melanogaster are used to estimate the effective population size of this species. PMID- 4029610 TI - Effects of pleiotropy on predictions concerning mutation-selection balance for polygenic traits. AB - Previous mathematical analyses of mutation-selection balance for metric traits assume that selection acts on the relevant loci only through the character(s) under study. Thus, they implicitly assume that all of the relevant mutation and selection parameters are estimable. A more realistic analysis must recognize that many of the pleiotropic effects of loci contributing variation to a given character are not known. To explore the consequences of these hidden effects, I analyze models of two pleiotropically connected polygenic traits, denoted P1 and P2. The actual equilibrium genetic variance for P1, based on complete knowledge of all mutation and selection parameters for both P1 and P2, can be compared to a prediction based solely on observations of P1. This extrapolation mimics empirically obtainable predictions because of the inevitability of unknown pleiotropic effects. The mutation parameters relevant to P1 are assumed to be known, but selection intensity is estimated from the within-generation reduction of phenotypic variance for P1. The extrapolated prediction is obtained by substituting these parameters into formulas based on single-character analyses. Approximate analytical and numerical results show that the level of agreement between these univariate extrapolations and the actual equilibrium variance depends critically on both the genetic model assumed and the relative magnitudes of the mutation and selection parameters. Unless per locus mutation rates are extremely high, i.e., generally greater than 10(-4), the widely used gaussian approximation for genetic effects at individual loci is not applicable. Nevertheless, the gaussian approximations predict that the true and extrapolated equilibria are in reasonable agreement, i.e., within a factor of two, over a wide range of parameter values. In contrast, an alternative approximation that applies for moderate and low per locus mutation rates predicts that the extrapolation will generally overestimate the true equilibrium variance unless there is little selection associated with hidden effects. The tendency to overestimate is understandable because selection acts on all of the pleiotropic manifestations of a new mutation, but equilibrium covariances among the characters affected may not reveal all of this selection. This casts doubt on the proposal that much of the additive polygenic variance observed in natural populations can be explained by mutation-selection balance. It also indicates the difficulty of critically evaluating this hypothesis. PMID- 4029611 TI - [Estimation of the parameters of the single-locus diallele model of qualitative trait in groups of relations]. AB - The method of estimation of parameters of monolocus diallele model (MDM) of qualitative trait on relative group data is described, these parameters being the number of affected and normal proband relatives of the arbitrary family degree and siblings in different matings types. For the case of single ascertainment, the expressions of corresponding probabilities have been taken as functions of MDM parameters using ITO matrixes and genetic transition matrix. Estimation of parameters was obtained by the maximum likelyhood method. Hardy-Weinberg equilibrium is not always necessary for this method; some weak requirement of stationarity is quite enough. PMID- 4029612 TI - [Families with recurrent cases of Waardenburg-Klein syndrome]. AB - Deaf children with the type I Waardenburg--Klein syndrome were studied. Secondary cases were found in 14 unrelated and 1 incest families. In 10 families probands and all their affected relatives had the type I Waardenburg--Klein syndrome. In 4 families patients were discovered with both type I and type II syndromes. In an incest family the proband seemed to have the type III, while his mother and father (sibs) had type II and their grandmother the type I syndrome. These results contradict the hypothesis claiming the origin of different types of Waardenburg--Klein syndrome to be due to the action of different genes. It is proposed that types I and II, or all types of the syndrome are caused by a single dominant gene. Potential mechanisms for clinical polymorphism of Waardenburg- Klein syndrome are related to incomplete penetrance and varying expression of this gene. PMID- 4029613 TI - Recombination between the t6 complex and linked loci in the house mouse. PMID- 4029614 TI - New ara-C resistant mutants of the Chinese hamster ovary cells. PMID- 4029616 TI - Polymorphism from environmental heterogeneity: models are only robust if the heterozygote is close in fitness to the favoured homozygote in each environment. PMID- 4029615 TI - Covariance between direct and maternal genetic effects in mice, with a model of persistent environmental influences. PMID- 4029617 TI - Observed relationships between protein heterozygosity and protein genetic distance and comparisons with neutral expectations. PMID- 4029618 TI - Genetic experiments on sisomicin production by Micromonospora rosea. PMID- 4029620 TI - Multiple-cloning-site plasmids for the rapid construction of recombinant poxviruses. AB - Plasmid vectors containing multiple cloning sites suitable for the rapid insertion of protein-coding sequences into poxviruses have been constructed. They are based on pUC plasmids and carry the thymidine kinase (TK) gene of vaccinia virus interrupted by a vaccinia virus promoter. Six unique restriction enzyme sites (BamHI, SalI/HincII, PstI, HindIII, EcoRI), located within 40 bp of vaccinia virus promoters transposed from the HindIII-F or HindIII-C fragment of the vaccinia virus genome, allow rapid insertion of foreign-protein-coding sequences into these plasmids. Such plasmids can be used to construct recombinant poxviruses expressing foreign proteins using marker-rescue recombination techniques and selection for TK negative viruses. Vaccinia viruses expressing the haemagglutinin (HA) gene of swine influenza virus, A/NJ/11/76 (H1N1), have been constructed. PMID- 4029619 TI - Characterization of the Trypanosoma brucei 5S ribosomal RNA gene and transcript: the 5S rRNA is a spliced-leader-independent species. AB - Recent studies have shown that transcription occurs discontinuously for many genes in Trypanosoma brucei. To further investigate details of transcription in trypanosomes, the genes for the 5S ribosomal RNA from Trypanosoma brucei rhodesiense and Trypanosoma brucei brucei were cloned. Sequence analysis and Southern blotting showed the genes to be arranged in highly conserved tandem repeats of approx. 740 bp, which have no relation to the conserved 35-base spliced-leader repeat element. The genes contain internal control regions similar to 5S genes of other species, and studies of the 5S gene transcript show that it does not contain the conserved 35-base spliced-leader found at the 5' end of other trypanosome transcripts. Moreover, the 5S rRNA can be capped by guanylyltransferase from vaccinia virus, indicating that it has a 5' di- or triphosphate terminus. These results strongly suggest that the spliced-leader does not take part in the transcription of the 5S gene and that discontinuous transcription may be limited to particular classes of transcripts determined, as in other species, by the type of RNA polymerase used in their transcription. The DNA sequences of the 5S gene repeat from T.b. brucei and T.b. rhodesiense are presented, and their evolutionary significance is discussed. PMID- 4029621 TI - Nucleotide sequences in human chromosomal DNA from nonhepatic tissues homologous to the hepatitis B virus genome. AB - DNA extracted from human nonhepatic tissues (placenta and kidney) have been digested with restriction endonucleases and examined by the Southern procedure with cloned 32P-labelled DNA of hepatitis B virus (HBV). In placental DNAs of women with the history of a hepatitis B infection and in one out of four cases of patients with no known HBV exposure or manifestation, HBV-related chromosomal nucleotide sequences were detected. The integration of HBV-related sequences was observed also in human kidney DNA. Moreover, in the placenta of women who had hepatitis B infection prior to delivery, unusual unintegrated forms of HBV have been found. We conclude that HBV sequences can be found not only in hepatic tissue but also in placental and kidney DNA, both of HBV-exposed and in one case even of a nonexposed patient. PMID- 4029622 TI - Decubitus ulcers: treatment through five therapeutic principles. AB - Without relief of localized pressure, no healing is possible, and all other therapeutic measures are futile. If other factors are mistakenly blamed (incontinence, perspiration, malnutrition) attention may be diverted from the essential--relief of localized pressure and maintenance of patient mobility. Dressings should protect healing ulcers from mechanical damage and external bacterial recontamination after removal of pathogens by local disinfection. Dressings should be kept moist with Ringer's solution to create conditions that promote new granulation. PMID- 4029623 TI - Geriatric hypertension controversies (Part I): Initial Tx. AB - The assumption that reducing blood pressure with drugs will be harmful or intolerable in older patients is not supported by treatment trials that have been reported to date. Patients treated nonpharmacologically need to be followed as closely as if they were receiving drug treatment. PMID- 4029624 TI - Diagnosing a common kidney infection of the elderly inpatient. AB - Initial antibiotic therapy should be based on Gram's stained urine. For the elderly patient with acute symptomatic bacterial pyelonephritis caused by gram negative aerobic bacilli, an aminoglycoside is recommended, eg, gentamicin, tobramycin, or amikacin. Pathologic pyuria (greater than 10 WBC/high-power field) supports the clinical impression of acute symptomatic bacterial pyelonephritis. However, many factors can spuriously lower the number of bacteria in the urine: prior diuresis or antimicrobials; obstruction distal to the site of infection; and infection not directly accessible to the collecting system. PMID- 4029625 TI - Will hospitals "take away" your geriatric patients? PMID- 4029626 TI - The ring of Soemmerring in the rabbit: A scanning electron microscopic study. AB - The scanning ultrastructure of the remnants of the lens left in the eye after extracapsular lens extraction was investigated in the rabbit. Extracapsular lens extraction was performed in 25 eyes and the development of after-cataract followed by biomicroscopic examination. After survival times varying between 1 week and 12 months, the eyes were enucleated and the rings of Soemmerring treated for light microscopy and transmission and scanning electron microscopy. Soemmerring's ring consisted of the fused remnants of the dissected anterior and posterior lens capsule, enclosing the equatorial part of the former lens, left behind after the operation. The anterior capsule and, to a lesser extent, also the posterior capsule were multilayered and appeared to be thickened. While the remnant of the anterior capsule was lined by a monolayer of epithelial cells, the posterior part of the capsule was only partly lined by irregularly arranged epithelial cells. All epithelial cells were highly vacuolized. In transection the interior part of the ring consisted of normal fibers, irregularly oriented and irregularly shaped fibers, degenerated fibers, and globular amorphous masses. Many of the normal fibers contained cell nuclei. At the equator and at the posterior side of the fusing anterior and posterior capsule as well, the fiber organization resembled the lens bow region of normal lenses. Frequently, islands of epithelial cells were observed in the center of the ring. The vitreal face of the posterior capsule in the center of the ring (in the optic axis of the eye) seemed to be unchanged and on its pupillary surface, fibers of different size as well as fibroblastlike cells were found. However, clear-cut Elschnig's pearls were absent. Our results are compared with the observations summarized in the literature. It can be concluded that the epithelial cells in Soemmerring's ring retain their capacity for division and differentiation. The newly formed fibers seem to be pushed to the center of the ring and to degenerate. PMID- 4029627 TI - Microproliferations in proliferative diabetic retinopathy and their relationship to the vitreous: corresponding light and electron microscopic studies. AB - Using a special embedding method, autopsied eyes with proliferative diabetic retinopathy were studied. In areas with no posterior vitreous detachment, small proliferations may arise multifocally and grow within the vitreous cortex. The fibrous material of the vitreous cortex is densely interconnected with and obviously incorporated into the newly formed proliferated tissue, a process which causes coarse traction lines on the vitreous cortex lamellae. The clinical consequences of these findings are discussed. PMID- 4029628 TI - Endothelial cell repopulation after intracameral acetic acid irrigation. AB - A significant, but transient corneal edema followed inadvertent intracameral irrigation of acetic acid in two patients. Since postsurgical corneal edema generally indicates corneal endothelial dysfunction, the effects of acetic acid on corneal endothelium were studied in the cat where the endothelial regenerative capacity is thought to be comparable to that of humans. The anterior chambers of feline eyes were irrigated with 0.25% acetic acid or balanced salt solution in a double-masked manner. Marked corneal opacification and thickening were evident following exposure to the acetic acid but did not occur following irrigation with balanced salt solution alone. Following intracameral acetic acid irrigation, a few endothelial cells were found in the anterior chamber angle but could not be found on Descemet's membrane. Over an 8-week period gradual repopulation of Descemet's membrane by endothelial cells occurred, first in the periphery and later in the central cornea, coincident with resolution of corneal edema. PMID- 4029629 TI - Collagen metabolism during the healing process of the cauterized rat cornea. An experimental study. AB - Attempts were made (1) to develop an appropriate method for producing standardizable and reproducible experimental opacities of the cornea of rats and (2) to study quantitatively the course and intensity of the healing process of these corneal wounds. The right cornea of rats was cauterized by drops of 1.5 N HC1 over 30 s; the left one served as a control. The spontaneous course of wound healing, as well as the possible effect on this process of spray treatment with iodine brine or, for comparative purposes, with isotonic NaCl, was studied for 10 consecutive days by measuring the 24-h incorporation of 14C-labelled proline as a measure of de novo collagen synthesis. Spray treatment (1) abolishes the transient inhibition of proline incorporation observed in the unsprayed cornea on the first day after injury and (2) significantly advances the maximum collagen synthesis rate from day 3-4 to day 2 after the wound occurred. The position and magnitude of the 14C-proline incorporation peak are considered to be useful parameters for estimating corneal wound healing activity and its alteration by various agents. However, in this experimental design, it could not be proved that iodine has a specific effect. PMID- 4029630 TI - Measurement of flow-physiologic parameters of retinal blood circulation in type 1 and 2 diabetics before and after photocoagulation. AB - In seven diabetics of type 1 and seven of type 2, the flow physiologic magnitudes were measured in a retinal quadrant before and after photocoagulation. The segmental blood flow, the arterial flow velocity, and the diameters of artery and vein are smaller after photocoagulation than before. Investigations into the time course of the flow-physiologic parameters following photocoagulation show that the flow-physiologic values are stationary about 2 weeks after photocoagulation. PMID- 4029631 TI - [Microbial contamination of seaside recreation areas and detection of risk factors for infectious diseases]. PMID- 4029632 TI - [Probability in the evaluation of the reliability of bactericidal effects]. PMID- 4029633 TI - [Psychophysiological criteria of the occupational suitability of adolescents for gas-arc welding]. PMID- 4029634 TI - [Physiological and hygienic evaluation of facilities for physical training in children's preschool institutions]. PMID- 4029635 TI - [Analysis of the time of death of animals with malignant neoplasms and various non-neoplastic forms of the late sequelae of external and internal irradiation]. PMID- 4029636 TI - [Beryllium in the external environment and in the human body]. PMID- 4029637 TI - [Toxicokinetics and metabolism of hexamethyldisilazane]. PMID- 4029638 TI - [Metabolic indicators in professional technical school students in relation to nutrition]. PMID- 4029639 TI - [Hygienic classification of carcinogenic substances and the potentials for its use in preventing carcinogenic exposures]. PMID- 4029640 TI - [Results and prospects of the hygienic standardization of the industrial microclimate]. PMID- 4029641 TI - [Hygienic aspects of an information model of noise]. PMID- 4029642 TI - [Function of the central and peripheral nervous systems in exposure to transportation noise of varying intensity]. PMID- 4029643 TI - [Classification of the hazards of the products from the thermal destruction of non-metal materials]. PMID- 4029644 TI - [Detoxication of dinitrophenol pesticides]. PMID- 4029645 TI - [Experience in researching the total impact of environmental factors on the health of children]. PMID- 4029646 TI - [Arterial pressure and autonomic regulation of the heart in students during academic activities]. PMID- 4029647 TI - [Evaluation of the performance reliability of power unit operators by physiological functions]. PMID- 4029648 TI - [Gas chromatographic determination of dicyclopentadiene in the air]. PMID- 4029649 TI - [Gas chromatographic determination of styrene in the air in the form of its dibromine derivative]. PMID- 4029650 TI - [Rapid method for determining the median lethal doses of chemical substances]. PMID- 4029651 TI - [Gas chromatographic determination of organic solvents in the air]. PMID- 4029652 TI - [Possibility for the quantitative assessment of human health]. PMID- 4029653 TI - [Hygienic prediction of the toxic substance content in the air indoors]. PMID- 4029654 TI - [Further comment on the publication No. 26 of the International Committee on Radiation Protection]. PMID- 4029655 TI - [Organizational aspects of nutrition of schoolchildren]. PMID- 4029656 TI - [Hygienic standards for the microclimate of manufacturing enterprises with an elevated heat release]. PMID- 4029657 TI - [Experience and outlook of research on chemical carcinogens in the environment]. PMID- 4029658 TI - [Content of nitroso compounds in fish from the central Ob River region]. PMID- 4029659 TI - [Survival of pathogenic Escherichia in the soil]. PMID- 4029660 TI - [Role of ice cream in cones in the epidemiology of enterobiasis]. PMID- 4029661 TI - [Establishment of the maximum permissible concentration of nitric oxide in the air of a work area]. PMID- 4029662 TI - [Comparative sensitivity of microorganisms to monochloramine B]. PMID- 4029663 TI - [Toxicological and hygienic characteristics of ortho- and para-anisidines]. PMID- 4029664 TI - [Hygienic establishment of the maximum permissible concentration of ortho phenylenediamine and methylcyancarbamate dimer in the water of reservoirs]. PMID- 4029665 TI - [Aerobic microflora of freshly caught and frozen food fish]. PMID- 4029666 TI - [Hygienic aspects in shaping the choice of job by school pupils]. PMID- 4029667 TI - [Metabolic characteristics of 99Mo in the blood]. PMID- 4029668 TI - [Information from the Soviet Toxicology Center]. PMID- 4029669 TI - Agency-family collaboration. PMID- 4029670 TI - Group psychotherapy with family caregivers of demented patients. PMID- 4029671 TI - The feminization of poverty and older women. PMID- 4029672 TI - There was nothing else to do: needs for care before nursing home admission. PMID- 4029674 TI - Nursing home friendships. PMID- 4029673 TI - Identification and ranking of stressors in nursing home administration. PMID- 4029675 TI - The natural history of nursing home patients. PMID- 4029676 TI - The social readjustment value of becoming a nursing home resident. PMID- 4029677 TI - Autonomy, power, and decision-making in thirty-six retirement communities. PMID- 4029679 TI - Grassroots advocacy for the elderly in small rural communities. PMID- 4029678 TI - Work, retirement, and well-being among unmarried men and women. PMID- 4029680 TI - [The psychological profile of the sterile couple and recommendations for its management]. PMID- 4029681 TI - [Isosexual precocious puberty caused by a bilateral follicular cyst]. PMID- 4029682 TI - [Fibrinogen/fibrin degradation products in the toxemic patient]. PMID- 4029683 TI - [Risk factors in the grand multipara]. PMID- 4029684 TI - [Risk factors in maternal death in hypertensive disease of pregnancy]. PMID- 4029685 TI - [Maternal mortality in the city of Villahermosa, Tabasco]. PMID- 4029686 TI - [Industrial hygiene problems in the mechanization of manufacturing]. PMID- 4029687 TI - [Determination of the effect of working conditions and the nature of the job on morbidity with temporary unfitness for work]. PMID- 4029688 TI - [Contact ultrasound and its hygienic importance as a factor of the industrial environment]. PMID- 4029689 TI - [Working conditions and the health status of glaziers in the construction industry]. PMID- 4029690 TI - [Assessment of the actual exposure of workers in contact with acrylonitrile]. PMID- 4029691 TI - [Characteristics of the toxic action of methacrylonitrile]. PMID- 4029692 TI - [Role of the industrial hygiene physician in the activities of a medical engineering team]. PMID- 4029693 TI - [Prevention of the cumulative manifestations of fatigue in sailors during prolonged cruises by means of electrosleep]. PMID- 4029694 TI - [Criteria of the adaptive reactions in workers manufacturing alkaline storage batteries]. PMID- 4029695 TI - [Experience in using low doses of ascorbic acid for reducing the morbidity of engine teams of the Moscow subway]. PMID- 4029696 TI - [Prospects for the sanitary improvement of the working conditions for wheel excavator operators at the Kansk-Achinsk Fuel and Power Complex]. PMID- 4029697 TI - [Gas chromatographic determination of trace amounts of NGZh-4 in the air of a work area]. PMID- 4029698 TI - [Gas chromatographic determination of isovaleraldehyde in the air of a work area]. PMID- 4029699 TI - [Gas chromatographic determination of benzyl alcohol, benzaldehyde and benzyl acetate in the air]. PMID- 4029700 TI - [A chamber for animal exposure to aerosols]. PMID- 4029701 TI - [Methodologic aspects of environmental protection]. PMID- 4029702 TI - [Health standards for electromagnetic fields: present status and outlook]. PMID- 4029703 TI - [Chromatographic method of determining the content of liquid gas constituents in the air of industrial establishments]. PMID- 4029704 TI - [Health status and problems of rehabilitation treatment of miners in the Baikal Amur Railway region]. PMID- 4029705 TI - [Methods of quantitative assessment of the entry of toxic substances into the body of workers by inhalation (using lead compounds as an example)]. PMID- 4029706 TI - [Physiologic health regulation of the labor of workers engaged in the maintenance of metallurgical furnaces and assemblies]. PMID- 4029707 TI - [Clinico-hygienic basis for improving the working and living conditions of geologists-geophysicists]. PMID- 4029708 TI - [Use of the toxicokinetic characteristics of styrene for the evaluation of its toxicity and health hazard]. PMID- 4029709 TI - [Use of the micronucleus test as a rapid method of detecting the potential carcinogenicity of asbestos-containing and other mineral fibers]. PMID- 4029710 TI - [Effect of personality traits of workers on the degree of their adaptation to a work situation involving conveyer production]. PMID- 4029711 TI - [Functional state of man during monotonous activity with varying physical loads]. PMID- 4029712 TI - [State of the hemolymph circulatory bed of the conjunctiva as affected by infrasound]. PMID- 4029713 TI - [Basis for the sanitary standard for ricid-II in the air of the working place]. PMID- 4029714 TI - [Quantitative assessment of the severity of damage caused by local vibration]. PMID- 4029715 TI - Diet and drinking habits in relation to the development of alcoholic pancreatitis. AB - To determine whether increased intakes of fat and protein or particular drinking habits are associated with the development of alcoholic pancreatitis, a dietary study has been conducted. Patients with clinically evident alcoholic pancreatitis were compared with individuals with clinically evident alcoholic cirrhosis with respect to dietary and drinking habits before the onset of clinical illness. There was no significant difference between the two groups regarding intake of nutrients, drinking habits or type of alcoholic beverage consumed. PMID- 4029716 TI - Impaired lipid clearance in patients with previous acute pancreatitis. AB - Fasting serum triglycerides were measured in 52 patients who had sustained an attack of pancreatitis (gall stone related 33, alcoholism six) at least six months earlier. Several patients (23%) had raised fasting serum triglycerides, with a type IV phenotype in all but one patient. The 40 patients with normal fasting serum triglycerides received an oral load of 100 g sunflower oil to compare their clearance of dietary triglycerides with that of a control group of 54 subjects. The clearance of ingested triglycerides was significantly impaired in the patients - irrespective of the presumed aetiological factor, or clinical condition associated with pancreatitis - compared with the clearance in controls. A triglyceride tolerance test is the only way to detect those patients in whom a future attack of pancreatitis may be precipitated by a diet rich in fat, or endogenous over production of triglycerides as after an alcoholic debauch. PMID- 4029717 TI - Intravenous omeprazole rapidly raises intragastric pH. AB - Twenty four hour intragastric acidity was measured in five duodenal ulcer patients studied at least three times. The effects of different dosage regimens of intravenous omeprazole was compared with placebo. Mean intragastric acidity from 1000 to 0800 was 34.3 +/- 4.3 mmol/l on placebo. After omeprazole 80 mg at 0900 and 40 mg at 1700 mean acidity was 2.1 +/- 0.9 mmol/l and after omeprazole 80 mg at 0900 and 80 mg at 1700 it was 0.7 +/- 0.2 mmol/l. pH remained above 4.0 for about 80% of recordings with these regimens and for only 5% with placebo. Three of the five patients also received omeprazole 80 mg at 0900, 40 mg at 1700 and 40 mg at 0100 when pH remained above 4.0 for 90% of recordings with 99% inhibition of acidity. Omeprazole rapidly raised intragastric pH in all patients and maintained a gastric pH of greater than 4.0 for most of the time. Large doses of IV omeprazole were required compared with studies using the oral compound. PMID- 4029718 TI - Influence of protein composition and hydrolysis method on intestinal absorption of protein in man. AB - An intestinal perfusion technique has been used in normal human subjects to investigate the influence that starter protein composition and hydrolysis procedure have on absorption of amino acid residues from partial enzymic hydrolysates of whole protein. Five starter proteins were studied. Three (egg albumin, casein/soy/lactalbumin, and lactalbumin) were hydrolysed by papain, a second lactalbumin starter protein, and a meat/soy/lactalbumin blend were hydrolysed by a porcine pancreatic enzyme system. Irrespective of starter protein composition or hydrolysis method used, four amino acid residues (threonine, glutamic acid, phenylalanine, and histidine) were absorbed significantly faster from all hydrolysates compared with absorption from their equivalent free amino acid mixtures. In contrast, both starter protein composition and hydrolysis method influenced absorption characteristics of up to nine other amino acid residues. PMID- 4029719 TI - Gastric acid secretion and gastrin production in the short bowel syndrome. AB - Excess gastric acid secretion and gastrin production may occur in patients with the short bowel syndrome but the two measurements have never been made simultaneously in man in response to a food stimulus. Using the technique of intragastric titration, this was carried out in eight patients after extensive small bowel resection resulting mainly from vascular occlusion and in eight matched normal control subjects. Basal acid output and peak acid output in response to pentagastrin was also measured separately. Although peak and integrated serum gastrin concentrations were significantly greater in patients (450 +/- SE 109 pg/ml; 113 +/- 2.9X10(-3) pg/ml/min) compared with control subjects (174 +/- 98 pg/ml; 6.1 +/- 2.0X10(-3) pg/ml/min p less than 0.05), no concomitant increase in acid secretion was shown either during intragastric titration or in response to pentagastrin. These findings indicate that there is no rationale for treating these patients with long term anti-ulcer therapy. PMID- 4029720 TI - Campylobacter colitis: histological immunohistochemical and ultrastructural findings. AB - The colonic biopsy specimens of 22 patients with colitis and positive stool cultures for Campylobacter jejuni were studied in order to obtain histological and immunohistochemical criteria to differentiate Campylobacter colitis from chronic inflammatory bowel disease. In addition we tried to identify Campylobacter inclusions by means of immunohistochemistry and electron microscopy as evidence for invasion of the colonic mucosa. The results show that the majority of patients with Campylobacter colitis have the histological picture of acute infectious colitis with increased numbers of IgA and IgM containing plasma cells in the colonic mucosa in contrast with patients with active chronic inflammatory bowel disease who show increases of IgA and IgG (ulcerative colitis) or IgA-, IgM and IgG containing plasma cells (M Crohn) in their colonic biopsies. The results of immunohistochemical stainings with Campylobacter antiserum show invasion of Campylobacter in the colonic mucosa. These findings were confirmed ultrastructurally. PMID- 4029721 TI - 111Indium autologous granulocytes in the detection of inflammatory bowel disease. AB - Indium leucocyte scanning and measurement of faecal Indium leucocyte excretion are techniques which have recently been introduced for assessing patients with inflammatory bowel disease. The methodology has recently been made more specific for acute inflammation by labelling pure granulocytes rather than the mixed leucocyte preparation. To determine the accuracy of this modified technique in detecting inflammatory bowel disease, we have prospectively compared Indium granulocyte scanning and faecal In granulocyte excretion with rectal histology and contrast bowel radiology as screening procedures in 100 patients with suspected inflammatory bowel disease. Thirty three patients were shown to have inflammatory bowel disease - 24 with Crohn's disease and nine with ulcerative colitis or indeterminate colitis. Overall the respective sensitivities for detecting inflammatory bowel disease were 97% for faecal Indium granulocyte excretion, 94% for Indium granulocyte scanning, 79% for radiology and 70% for rectal histology. The superiority of In granulocytes over radiology and rectal histology in detecting inflammatory bowel disease was, in the main, due to the difficulty in diagnosing Crohn's with conventional techniques. Although three of the patients with ulcerative colitis and indeterminate colitis had normal sigmoidoscopic appearances - all had abnormal rectal histology. No patient with a non-inflammatory bowel disorder had a positive In granulocyte scan or a raised faecal excretion. These results show that investigations using In granulocytes are accurate in identifying inflammatory bowel disease and offer important advantages over conventional procedures for detecting Crohn's disease. PMID- 4029722 TI - Drug therapy and perforated peptic ulcer. PMID- 4029723 TI - Modern trends in human leukemia VI. New results in clinical and biological research including pediatric oncology. PMID- 4029724 TI - Red cell transfusions for polytransfused patients. PMID- 4029725 TI - Empiric antimicrobial therapy in cancer patients. PMID- 4029726 TI - Prophylaxis of infection in granulocytopenic patients. PMID- 4029727 TI - Single donor platelet transfusion. PMID- 4029728 TI - Antiemetics in cancer chemotherapy. PMID- 4029729 TI - Chromosome abnormalities in malignant lymphoma: biologic and clinical correlations. PMID- 4029730 TI - Discrimination of leukemias, lymphomas, and non-neoplastic controls by retroviral serum markers. PMID- 4029731 TI - Cellular oncogenes as the ancestors of endocrine and paracrine growth factors and their evolutionary relic status in vertebrates. AB - Contrary to the popularly held view, genes that have lost their usefulness to the host organism may continue to encode proteins for 50 million years or longer. Accordingly, precisely regulated expression of genes can not be taken as proof of their indispensability. My view is that multitudes of oncogenes of vertebrates are evolutionary relics harking back to the days of invertebrate ancestors in which embryogenesis was still a cell autonomous process. Parts of certain oncogene coding sequences originated from repeats of base oligomers whose numbers of bases were not multiples of three. Thus, these segments are still endowed with a measure of immortality in that they are impervious to normally very deleterious base substitutions, insertions, and deletions. PMID- 4029732 TI - The genes that carcinogens act upon. PMID- 4029733 TI - Tumors induced in hairless mice by DNA from human malignant cells. PMID- 4029734 TI - Normal regulators of growth and differentiation and the reversal of malignancy in leukemia. PMID- 4029735 TI - Self-renewal of haemopoietic stem cells: the roles of the environment, of growth factors and of the src oncogene. PMID- 4029736 TI - Proliferation in vivo and in vitro of haemopoietic progenitor cells induced by AF 1, a new ras-containing retrovirus. PMID- 4029737 TI - Evidence of Sternberg-Reed cells being derived from activated lymphocytes. PMID- 4029738 TI - Lymphocyte and lymphoma receptors utilized in differentiation, in homing, and in lymphomagenesis. PMID- 4029739 TI - Influence of colchicine and cytochalasin B on pinocytosis, phagocytosis, and antibody-dependent cell-mediated cytotoxicity. PMID- 4029740 TI - In vivo studies with covalent conjugates of cobra venom factor and monoclonal antibodies to human tumors. PMID- 4029741 TI - Mechanisms of drug resistance in human leukemia. PMID- 4029742 TI - [In vitro fertilization in reduced male fertility]. PMID- 4029743 TI - [Therapeutic guidelines for gynecologic-andrologic consultation]. PMID- 4029744 TI - [Therapeutic course with childless couples with special reference to the interrelation among 4 persons in gynecologic-andrologic consultations]. PMID- 4029745 TI - [Introduction to the gynecologic-andrologic consultation]. PMID- 4029746 TI - [New results in the morphologic diagnosis of spermatogenesis disorders]. PMID- 4029747 TI - [Microsurgical fertility operations in the male]. PMID- 4029748 TI - [Spermatozoa-cervical mucus interaction: diagnosis and significance]. PMID- 4029749 TI - [Capacitation and oocyte penetration of spermatozoa]. PMID- 4029750 TI - Follow-up of growth-retarded children born by elective cesarean section before 33 weeks. AB - 25 singleton pregnancies were terminated by cesarean section between 28 and 33 weeks of gestation because of suspected growth retardation and abnormal unstressed cardiotocograms. Only infants with birth weights below the tenth centile were considered. 17 survived and were neurologically examined at 2.5-7 years of age. 2 were neurologically abnormal (1 had an adrenogenital syndrome) and 1 showed minor neurological dysfunction. Cesarean section appears acceptable in the management of intrauterine growth retardation with fetal distress in the early third trimester. PMID- 4029752 TI - Arginine vasopressin in amniotic fluid, arterial and venous cord plasma and maternal venous plasma. AB - High concentrations of arginine vasopressin (AVP) in arterial umbilical cord blood at the time of delivery have been attributed to either a generalized increase in the activity of the fetal endocrine system at the onset of labor or to fetal asphyxia. We measured AVP in amniotic fluid, arterial and venous cord blood and in maternal venous blood from 13 patients at 38-40 weeks of gestation at the time of elective cesarean section with a nonasphyxic fetus (group I), in amniotic fluid from 19 patients at 15-17 weeks of gestation (group II) and in venous blood from 13 nonpregnant control subjects (group III). Our results showed a high concentration of AVP in the amniotic fluid both in the middle and at the end of normal pregnancy and at the same level as in arterial cord blood, whereas AVP in the venous cord blood was significantly lower and at the same level as in the maternal venous blood and in the control group. It is concluded that the fetus produces AVP and this is at least not solely caused by fetal asphyxia or related to parturition. PMID- 4029751 TI - Some new aspects on emesis gravidarum. Relations to clinical data, serum electrolytes, total protein and creatinine. AB - Although nausea and vomiting in early pregnancy is extremely common, very little information on the cause and course of this disorder is available in the literature. A prospective laboratory and clinical study of 102 consecutive healthy pregnant women was undertaken to evaluate nausea and vomiting in relation to clinical data, serum electrolytes, creatinine, total protein and hemoglobin. Multigravidae suffered from emesis gravidarum at a higher rate than did primigravidae. The frequency of emesis was especially high in women with short intergestational intervals. During pregnancy there was a decline in systolic blood pressure only in non-emetic women. The diastolic blood pressure in late pregnancy was significantly higher in emetic women than in non-emetic subjects. All laboratory values were within normal ranges. However, major changes occurred during pregnancy but some alterations were noted only in the emetic pregnancy. A different response to the hormonal situation is suggested to explain the dissimilarities between the emetic and non-emetic pregnancy. PMID- 4029753 TI - Lipid and lipoprotein levels following pure estradiol implantation in post menopausal women. AB - 8 post-menopausal, post-oophrectomy and hysterectomy women had a 100-mg pure 17 beta-estradiol pellet installed in their subcutaneous abdominal tissue. The pellet caused a marked systemic hormonal effect in these patients causing an up to 30-fold increase in plasma estradiol and a marked decrease in follicle stimulating hormone levels. It showed a significant increase in plasma high density lipoprotein (HDL) and HDL to total cholesterol ratio levels, no change in plasma triglycerides and very low density lipoprotein levels and some decrease in total cholesterol and low density lipoprotein cholesterol concentrations. These results differ from the previously reported influence of synthetic hormonal preparations on the same plasma lipids and lipoproteins. PMID- 4029754 TI - Chromatographic techniques for the separation of a thrombocytopoiesis-stimulating factor from aplastic rats. AB - Thrombocytopoietin seems to be only partially responsible for the regulation of platelet production. We determined precisely the differences between a second thrombocytopoiesis-stimulating factor (TSF2), and thrombocytopoietin (TSF1) and erythropoietin (Epo). Fractionation was carried out, first on a DEAE-cellulose phosphate column and then on a Sephadex G-75 column. Thrombocytopoietic activity in the various fractions was assessed using 75Se-methionine platelet incorporation into normal recipients. Epo concentrations were determined using a radioimmunoassay. We showed that the apparent molecular weight of TSF2 is 14,000 daltons. It differs from TSF1 (48,000 daltons) and from Epo (39,000 daltons). For doses of 8-12 mU Epo/rat, found in whole serum injected, no effect on thrombocytopoiesis was found. On the contrary, a significant effect (p less than 0.01) was found when the same quantities of Epo present in the Sephadex G-75 F4' fraction were injected (2-10 mU/rat). TSF2 can be separated from TSF1 and Epo, using biochemical techniques. PMID- 4029755 TI - Kinetics of urokinase-induced thrombolysis in a biphasic in vitro system. AB - The role and effect of added lys-plasminogen (lys-PLG) on urokinase-induced thrombolysis in an in vitro biphasic system were investigated. The kinetics of lysis of whole blood thrombi was followed in perfusion mediums of normal plasma, PLG-deficient plasma and normal saline using a high and a low concentration of urokinase (UK). The lysis of standard whole blood thrombi in whole blood perfusion mediums to which had been added UK alone or UK plus lys-PLG was compared to whole blood thrombi enriched with lys-PLG by incorporation during thrombus formation or by adsorption during perfusion. In addition, the kinetics of lysis of PLG-deficient fibrin thrombi perfused in PLG-deficient plasma or normal saline was studied when lys-PLG had been added to the thrombus, to the perfusion medium or to both thrombus and medium. In PLG-deficient plasma from which plasmin inhibitors had not been removed, thrombolysis was minimal even at a high concentration of UK. This effect could be neutralized, and to some extent, regulated, by lys-PLG enrichment of the medium. Both PLG-incorporated and PLG adsorbed whole blood thrombi gave initial and sustained acceleration of UK induced lysis in comparison with standard nontreated thrombi. It is concluded that in a blood-thrombus biphasic thrombolytic system induced by UK, there is interaction between the phases, and that PLG in both phases influences thrombolysis. PMID- 4029756 TI - Correlation between hepatic blood flow and coagulation indices in chronic active hepatitis and liver cirrhosis patients. AB - Hepatic blood flow (HBF) has been reported to reflect liver cell mass. HBF was studied in 21 patients with chronic active hepatitis (CAH) and in 20 patients with liver cirrhosis (LC). It was correlated with such indices of liver protein synthesis as serum albumin, Normotest, plasma activity of antithrombin III, prekallikrein, alpha 2-antiplasmin and plasminogen. No correlation between HBF and the examined parameters was seen in CAH. HBF correlated with all the indices of liver protein synthesis in LC, thus suggesting that serum albumin, antithrombin III, Normotest, prekallikrein, plasminogen, and alpha 2-antiplasmin could reflect the residual liver cell mass in LC. PMID- 4029757 TI - Combined dys-form of homozygous factor XI deficiency and heterozygous factor XII deficiency. AB - A 12-year-old girl with lifelong hemorrhagic episodes was found to have both a dys-form of homozygous factor XI deficiency and heterozygous factor XII deficiency. The heredity of the coagulation defects was confirmed by family studies. Severe bleeding after dental surgery occurred in spite of replacement therapy and local measures including fibrin glue. Our findings suggest that the risk of bleeding in patients with homozygous factor XI deficiency must not be underestimated and that the most effective measure is the transfusion of sufficient amounts of fresh frozen plasma until at least the 5th postoperative day. PMID- 4029758 TI - Bone marrow patterns in chronic lymphocytic leukaemia related to various clinical and haematological findings. A preliminary report. AB - In a retrospective study of 55 CLL cases subjected to bone-marrow biopsy, the histological pattern of the bone-marrow was correlated to the clinical and haematological data. Instead of the four histological patterns described by Rozman et al., five patterns have been established. The clinical staging according to the Montserrat score, compared with the bone-marrow pattern, showed a good correlation, when maintenance or replacement of normal haematopoiesis was considered. The bone-marrow pattern with maintained haematopoiesis was predicting a favourable clinical correlation; those with replaced haematopoiesis corresponded to a poor prognosis. The correlation is a useful index of severity and prognosis of CLL. PMID- 4029759 TI - The heparin binding proteins of sarcoma induced by methylcholantrene in rats. AB - The proteins binding and neutralizing the heparin of sarcoma induced by methylcholantrene are basic proteins. They are a mixture of at least three different proteins, possessing cathodic mobility in polyacrylamide gel electrophoresis of pH 2.7 and having a low molecular weight. PMID- 4029760 TI - Electrochromatographic analysis of abnormal serum proteins. AB - An electrochromatographic method for the analysis of sera is described with particular design to studies of abnormal proteins. The method allows a simultaneous but independent evaluation of molecular weight and charge related migration of proteins. A modification which may improve the analysis of immunoglobulins by increasing their electrophoretic mobility is described. PMID- 4029761 TI - [Thoracic outlet syndrome and its significance for surgery of the hand (on the etiology and pathogenesis of epicondylitis, tendovaginitis, median nerve compression and trophic disorders of the hand)]. AB - At present, the term "thoracic outlet syndrome" (TOS) is used as a term to include all factors compressing the nerves and vessels situated in the outlet of the thorax and the costo-clavicular area. It is marked by neurological and vascular disorders; their manifestation can be either spontaneous or posttraumatic. In case of surgical treatment the transaxillary approach (according to Roos) proved to be the best, and is indicated in therapy-resistant TOS, in certain cases of arterial complications and in outlet obstructions of the subclavian vein. Complete resection of the first rib and the most careful removal of all fibro-muscular structures affecting the artery, vein and brachial plexus are of importance to the result of the operation. In the evaluation of cases we found surprising success with cases of lateral epicondylitis. Thus, the nerve irritation asserted as a cause in 1962 is once more confirmed. The postoperative development of 38 median nerve compressions proved to be particularly astonishing. Twenty-five of those vanished without any need for additional measures, and in eight cases definite improvement was achieved. Another important fact was observed when five median nerve compressions, previously operated upon, disappeared only after a secondary TOS-operation. These observations led to a new pathogenetic concept of median nerve compression. Apart from the common causes, the primary predisposing factor for median nerve compression is a chronic oedema due to a functional blockage of the subclavian vein, clinically and radiologically substantiated. This oedema eventually leads to a carpal tunnel syndrome, either directly on account of swelling of fibrous structures or via metabolic disorders and oxygen deficiency, thereby causing an infiltrative and proliferative reaction. In this connection, it seems interesting that the results of recent pathohistological researches suggest that the chronic oedema is the greater pathogenetic factor. The improvement of painful tendovaginitis and different disturbances in wound healing after surgical treatment of the TOS shows the importance of subclavian vein compressions. Phlebographic examination of patients who suffer from Sudeck's atrophy demonstrates significant narrowing of the subclavian vein. The increasing pressure in the subfascial space and the irritation of the lower cervical plexus and the subclavian artery can promote Sudeck's atrophy. PMID- 4029762 TI - [Carpal instabilities]. AB - The ligaments of the wrist and the bony configuration--beside muscles and tendons -are responsible for stability in the wrist joint, which is impaired in certain pathological conditions: unstable fractures of the scaphoid, scapholunate dissociations, perilunate fracture-dislocations, malunited Colles' fractures, Kienbocks disease, rheumatoid arthritis and posttraumatic laxity of ligaments. The differentiation between dorsal and palmar instability is made by radiological examination and measuring of the scapholunate, capitolunate and radiolunate angles. The understanding of normal anatomy and (post-)traumatic conditions is facilitated by the concept of dynamic action of the ligaments and the bones of the wrist as articular and extraarticular slings. PMID- 4029763 TI - [Scapholunate dissociation]. AB - Scapholunate dissociation is a rotatory subluxation of the scaphoid with widening of the gap between the scaphoid and lunate. It is caused by rupture of the ligaments between radius, scaphoid, lunate and capitate bones. The scaphoid has lost its stabilizing function as a bridge between the proximal and distal carpal row, so that the wrist shows the typical "concertina" deformity of dorsal instability. The scapholunate angle measures about 100 degrees (more than 70 degrees). The subluxation of the scaphoid and lunate with the wide gap between these bones is best treated by primary repair of the ruptured ligaments. However, most cases are seen late and a ligament reconstruction by a free or pedicled tendon graft becomes necessary. The results are often unsatisfactory radiologically, but cause the patient minimal disability. An alternative to the ligament reconstruction is the scapho-trapezio-trapezoid arthrodesis. By this procedure the scaphoid regains its stabilizing function to the "link system" of the carpus. PMID- 4029764 TI - [Dorsal ligament reconstruction in scapholunate dissociation]. AB - After discussion of the importance of the palmar, dorsal and interosseous ligaments in cases of scapholunate subluxation, the radiologic signs of this carpal instability are described. Four cases with this instability were treated successfully by reconstruction of the dorsal ligaments. In three instances ligament reconstruction was performed with the split tendon of the extensor carpi radialis brevis passed through drill holes in the scaphoid and lunate similar to the method reported by Dobyns. PMID- 4029765 TI - [Damage of the wrist. Prosthetic replacement and alternatives]. AB - Defects in the wrist and carpal bones, caused by trauma or disease, can be treated by denervation, resection-arthroplasty, arthrodesis or prosthetic replacement. In the last few years the use of the alloplasty has developed slowly in the German speaking countries. As in the American Field Clinic, surgeons should evaluate all their cases by the same criteria. Wrist: 109 prostheses were implanted by six surgeons, 51 Meuli-prostheses, one Gschwend-design and 57 Swanson-spacers. The spacer seems to be simpler and less complicated. Such complications were encountered in 40% of the prostheses, but in only one with the spacer. The scaphoid replacement, of which 227 cases are described by ten surgeons, is the most widely used in our countries. The main risk is subluxation, caused by technical errors or use of an incorrect size of spacer. The complication rate varies from seven to fourty percent. The lunate replacement- 140 cases by twelve surgeons--is less common, probably because of initial failures. Correct implantation and size of the spacer are necessary for good results. Complication rate varies from 6.4 to 55 percent. A high percentage of failures is attributable to lack of operative experience. Koob is the only one who has experience with his own design "Essen". A long-term follow-up of sixteen cases shows failures in two cases, but an increase of arthrosis. PMID- 4029766 TI - [Technic and results of tendon interposition arthroplasty of the lunate and scaphoid bones]. AB - Between 1971 and 1982 tendon interposition arthroplasty in combination with denervation of the wrist joint was performed on 55 patients with either Kienbock's disease, irreducible lunate dislocations with or without scaphoid dislocation, or scaphoid non-union with a small proximal fragment. Follow-up was possible on 38 patients (69%). In two third of the cases good and very good results are achieved with this operative technique. The significant points were the arthrosis in the wrist joint and the complete obliteration with tendon material of the cavity left by the extirpated carpal bone. Ulnar styloidectomy produced not only a painfree wrist but also better ulnar movement. PMID- 4029767 TI - [Proximal radial nerve compression syndrome. Treatment and results]. AB - Radial palsy after a single brisk contraction of the triceps muscle was first described by Gowers in 1892. The cause of such paralyses, which also can be found after chronic overexposure, in the course of fracture healing and because of inflammation or tumors, has not been explained until 1969. Two mechanisms are of importance for pressure effects on the radial nerve; either the nerve can be compressed in the hiatus nervi radialis due to swellings or a direct lesion occurs. The latter can happen because of a sudden brisk muscle contraction or on account of chronic trauma caused by the lateral head of the triceps. Since 1969, twenty patients with such radial nerve compressions have received surgical treatment and follow-up in our clinic. PMID- 4029768 TI - [Indications and results of corrective radius operations]. AB - Posttraumatic malunion usually results from incorrect treatment of a Colles or Smith fracture. Chronic pain, limited motion and impaired power can be avoided and the cosmetic appearance of the hand improved, by restoration of the functional anatomy of the wrist. The malalignment is corrected by open wedge osteotomy of the distal end of the radius. A small iliac cortico-cancellous bone graft is inserted at the osteotomy site. By using this technique, it is usually possible to avoid additional resection of the distal ulna. The surgical approach dorsal or palmar is determined by the type of dislocation. The small T-plate offers a stable fixation. The results are illustrated by 41 cases. PMID- 4029769 TI - [Septic arthritis of the finger joints. Treatment with immediate arthrodesis]. AB - A consecutive series of 44 patients with septic arthritis of finger joints is presented. The patients were treated with antibiotics, incision, debridement and usually drainage. In 13 patients with destruction of the joint cartilage, an arthrodesis was made at the time of incision. The failure rate with conventional therapy was 42 per cent. The failure rate in the arthrodesis group, which represented all the severe cases, was 23 per cent. In septic arthritis of finger joints with destruction of the cartilage arthrodesis with Kirschner-wire and interosseous wiring is recommended at the time of primary incision. PMID- 4029770 TI - [Results of replantation in thumb amputations. New examination methods for evaluation of sensation]. AB - Of 91 thumb amputation injuries which were treated over a five-year period at the Department of Traumatology, University School of Surgery Homburg/Saar, 56% could be subjected to a critical follow-up evaluation. The evaluation scheme of Millesi "Evaluation and Registration of Hand Function" programmed for electronic data processing forms the basis for the study. Besides the specified criteria for sensitivity testing, a further method for objective testing is presented. The principle of this method is point stimulation of pressure and mechanoreceptors after eliciting a threshold perceptible vibration stimulus of an 80 Hz sinusoidal oscillation the intensity of which can be directly measured as a yardstick for the stimulus response. Electronic processing of all results of the patients investigated shows that the injured hand can be used to almost 100% in 38%. In 16 patients (31%), there is a reduction by 5 to 20%. In ten cases (20%), the reduction was rated as over 20% compared to a healthy hand and in 11% (six patients), the overall result is to be designated as poor with more than 40% reduction of use. PMID- 4029771 TI - [Post-radiation brain necrosis]. PMID- 4029772 TI - [Involvement of families in the treatment of combat reaction casualties in the lebanese War of 1982]. PMID- 4029773 TI - [Cardiac tamponade as a presentation of metastatic extracardiac malignancy]. PMID- 4029774 TI - [Reconstruction of the small joints of the hand by perichondrial arthroplasty]. PMID- 4029775 TI - [Superior mesenteric artery syndrome in acute traumatic paraplegia]. PMID- 4029776 TI - [Neonatal sepsis, meningitis and lobar pneumonia due to Streptococcus pneumoniae]. PMID- 4029777 TI - [Osteomyelitis of the vertebrae as the result of urinary infection]. PMID- 4029778 TI - [Clinical decisions under uncertainty: a proposal for an undergraduate course in medicine]. PMID- 4029779 TI - [Ocular damage in the laser industry]. PMID- 4029780 TI - [Familial aggregation, heritability and heterogeneity in common diseases]. PMID- 4029781 TI - [Food allergy]. PMID- 4029782 TI - [Assessment of fetal movements in the prevention of intrauterine fetal death]. PMID- 4029783 TI - [Epidemic of acquired immunodeficiency syndrome triggering psychotic-psychogenic reactions]. PMID- 4029784 TI - [Neodymium-YAG laser, a non-invasive technique for cutting intraocular tissues]. PMID- 4029785 TI - [Peritoneal mesotheliomas and exposure to asbestos]. PMID- 4029786 TI - [Colchicine overdose]. PMID- 4029787 TI - [Delayed respiratory depression after epidural morphine]. PMID- 4029788 TI - [Fatal anaphylaxis in systemic mastocytosis]. PMID- 4029789 TI - [Pernicious anemia masked by B-thalassemia trait in two young Israeli Arabs]. PMID- 4029791 TI - [Local amyloidosis]. PMID- 4029790 TI - [Delayed neurotoxicity by organophosphorus compounds]. PMID- 4029792 TI - [Aminoglycosides]. PMID- 4029793 TI - [Rectal prolapse in childhood]. PMID- 4029794 TI - [The eosinophil: a helper or an aberrant cell?]. PMID- 4029795 TI - [Acquired immune deficiency syndrome--update]. PMID- 4029796 TI - [Foot blood flow in diabetic neuropathy]. PMID- 4029797 TI - [Amiodarone pulmonary toxicity]. PMID- 4029798 TI - Legislating health care coverage for the unemployed. AB - Because the unemployed and their families are often likely to develop stress related health problems, ensuring them access to health care is a public health issue. Congressional efforts thus far to legislate health coverage for the unemployed have proposed a system that recognizes people's basic need for coverage but has several limitations. PMID- 4029800 TI - Protective services teams: the social worker as liaison. AB - Multidisciplinary teams are widely used in response to complex problems such as child abuse, but they involve areas of potential conflict. Using his experience as a public agency liaison to the protective services team of a major children's hospital, the author examines how the liaison role combined with social work skills can help reduce conflict and enhance the performance of such teams. PMID- 4029799 TI - At risk: health needs of Hispanic children. AB - Assessing the needs of vulnerable populations and targeting services for them requires a thorough examination of the special risks they face. This article identifies the psychosocial risks of Hispanic children, emphasizing that cultural, psychological, and economic factors interact to jeopardize the health and educational development of this rapidly growing segment of the population. PMID- 4029801 TI - Chronic pain and marital difficulties. AB - Chronic pain in one of the partners in a marriage causes profound changes in the marital relationship: roles and communication patterns are transformed, sexual relationships deteriorate, and the well partner frequently succumbs to distress and illness. In examining these changes, this article highlights the need for routine marital and family assessment and a family treatment approach for patients and their spouses. PMID- 4029802 TI - Discharge planning as a teaching mechanism. AB - A framework that organizes content into performance objectives is presented for planning field instruction and in-service education. Intended to overcome the polarization between concrete services and therapeutic intervention frequently seen within the profession, the objectives highlight the social work knowledge and skills inherent in discharge planning to encourage learners to appreciate this sometimes deprecated but increasingly important function. PMID- 4029803 TI - Social work with laryngectomees. AB - Laryngeal cancer has a high survival rate, yet the loss of the natural voice and a host of physical and psychosocial problems make recovery especially difficult. Written according to the outline followed by the articles in Health and Social Work's November 1981 Supplement on Specialization and Specialty Interests, this article provides a social work perspective on the needs, care, and rehabilitation of laryngectomy patients. PMID- 4029804 TI - [Changes in the biosynthetic activity of gastric glycoproteins during the healing process of acetic acid ulcer in rats]. AB - Changes in the incorporation of 3H-glucosamine into the macromolecular glycoprotein during the healing process of acetic acid induced gastric ulcer in rats were sequentially examined in the ulcer region and the intact region at 2, 10, 40, 80 and 365 days after the operation. 1) The total radioactivity (Tissue + Medium) and the radioactivity which remained in the tissue after incubation of the ulcer region were increased significantly as compared with those of the control at 2 days after the operation (275, 175% of the control, respectively), and then total radioactivity returned to the control level. On the other hand, the radioactivity in the tissue was gradually decreased, and then it became 50% of the control at 365 days. In contrast, the incorporating activity into the macromolecular glycoproteins was decreased to 50% of the control at 2 days, and was once recovered to the control level at 10 days. After 40 days, it was again decreased to 50% of the control and became 30% at 365 days. 2) Changes in the incorporation of 3H-glucosamine into the macromolecular glycoproteins of the intact region of rats with ulcers were the same as that of the ulcer region. 3) Elution profiles of gel filtration of the macromolecular glycoproteins isolated from the relapse and recurrence region of rats with ulcers at 365 days were the same as that of the healing region, and their radioactivities were decreased to 30% of the control. The results suggested that such a decrease in the biosynthetic activity of the macromolecular glycoproteins extending over the whole gastric tissue is one of the reasons for the increased relapse and recurrence. PMID- 4029805 TI - [Effects of isosorbide 5-mononitrate on cardiovascular function. (I). Effects on the left ventricular system]. AB - Effects of isosorbide 5-mononitrate (5-ISMN) on cardiovascular function were compared with those of isosorbide dinitrate (ISDN), verapamil and propranolol. In anesthetized open-chest dogs, intravenous injection of 5-ISMN (1 mg/kg, 3 mg/kg) scarcely decreased cardiac contractile force (CCF) and heart rate (HR). The systolic blood pressure (SBP) fell in a dose-dependent manner, and the degree of the change was greater than that in diastolic blood pressure (DBP). Especially, left ventricular pressure (LVP) and left ventricular dp/dt (LVdp/dt) were significantly decreased, and a considerable reduction in left ventricular end diastolic pressure (LVEDP) was also observed. Intravenous injection of verapamil (0.3 mg/kg) considerably lowered DBP. While HR, CCF, LVP and LVdp/dt were markedly decreased, LVEDP showed a moderate increase. Propranolol (0.5 mg/kg, i.v.) greatly decreased LVdp/dt together with HR and CCF. Conversely, LVEDP showed a slight increase. There was no change in SBP, DBP and LVP. The vasodilating potency of 5-ISMN was 150 times smaller than that of ISDN on the contractile response in isolated rabbit thoracic aorta. On the other hand, in terms of decrease in pulse pressure, the potency exhibited by 5-ISMN was about 4 times (intravenous administration in anesthetized dogs) or 1.5 times (oral administration in conscious dogs) smaller than that of ISDN. The present results suggest that 5-ISMN shows a high bioavailability and a potency comparable to ISDN, especially in the case of peroral administration. Taking these results together with the fact that transient left ventricular failure occurs during myocardial ischemia into consideration, it is thought that peroral 5-ISMN preparation may be useful in the therapy of angina pectoris. PMID- 4029806 TI - [Antiedema effects of basic nonsteroidal anti-inflammatory drugs that are not inhibitors of prostaglandin biosynthesis]. AB - Antiedema effects of basic nonsteroidal anti-inflammatory drugs that don't inhibit prostaglandin biosynthesis were investigated with carrageenin-induced hind paw edema in rats. Locally administered mepirizole, tiaramide.HCl and aminopyrine, the basic nonsteroidal anti-inflammatory drugs, didn't show any suppression against the edema formation. In the case of indomethacin, phenylbutazone and ketoprofen, inhibitors of prostaglandin biosynthesis, they inhibited the edema formation. Inhibitory effects of orally and subcutaneously administered basic nonsteroidal anti-inflammatory drugs such as tiaramide.HCl and benzydamine on the edema formation were more potent in fasted rats than in nonfasted rats. In the case of acidic nonsteroidal anti-inflammatory drugs such as indomethacin and ibuprofen, their inhibitory activities were almost the same in both the fasted rats and nonfasted rats. These results suggest that the site of action of the basic nonsteroidal anti-inflammatory drugs such as tiaramide.HCl and mepirizole is not the inflamed site, and certain systemic effects may contribute to the anti-edema effects. PMID- 4029807 TI - [Experimental nephrotic hyperlipidemia induced in rats by daunorubicin and effects of KCD-232[4-(4'-chlorobenzyloxy)benzyl nicotinate] on lipid metabolism]. AB - Mechanisms for hypercholesterolemia and hypertriglyceridemia and the effects of KCD-232, a new hypolipidemic agent, on them were studied in male Wistar rats with daunorubicin (DR)-induced nephrosis. Single intravenous injection of DR dose dependently increased urinary protein loss and serum lipid levels (0,3,6 and 12 mg/kg). Twenty-four days after the injection of DR (6 mg/kg), serum cholesterol (Ch) and triglyceride (TG) levels markedly increased and free fatty acid level tended to decrease with no effects on liver lipid levels. Hepatic Ch synthesis from [14C]acetate in vitro increased by 2.1-fold, while exogenous Ch absorption slightly decreased. The clearance of intravenously injected [3H]Ch from the circulation was delayed. Hepatic fatty acid (FA) synthesis also increased by 2.7 fold, and hepatic TG lipase activity tended to decrease. KCD-232 improved the hypercholesterolemia and hypertriglyceridemia of DR-treated rats. The drug inhibited the elevated hepatic Ch synthesis and exogenous Ch absorption and thus improved the delayed Ch clearance from the circulation. KCD-232 markedly inhibited the elevated hepatic FA synthesis and stimulated both hepatic FA oxidation and lipoprotein lipase activity from the epididymal adipose tissue of the nephrotic rats. These results suggest that 1. DR-induced hypercholesterolemia is due to both an increased Ch synthesis in the liver and delayed clearance of Ch from the circulation; 2. DR-induced hypertriglyceridemia is caused by both an increased hepatic FA synthesis and depressed TG hydrolysis in the circulation; 3. KCD-232 improves the hypercholesterolemia by inhibiting the elevated Ch synthesis and Ch absorption from the gut; and 4. KCD-232 improves the hypertriglyceridemia by inhibiting the elevated hepatic FA synthesis and by stimulating both hepatic FA oxidation and TG hydrolysis activity in the circulation. PMID- 4029808 TI - [Pharmacokinetic and pharmacological studies on cetraxate, an anti-ulcer agent]. AB - Cetraxate hydrochloride was administered either orally or intravenously to rabbits, and its concentration in body fluids was determined by using the HPLC method. Cetraxate was easily hydrolyzed in the gastrointestinal tract and blood, and it was metabolized to p-hydroxyphenylpropionic acid (PHPA) and a new metabolite, p-hydroxybenzoic acid (PHBA). After oral administration of cetraxate hydrochloride, a large amount of unchanged drug was distributed to the gastric wall. PHPA was distributed in all the organs examined, excluding the brain. To determine whether or not the anti-ulcer action of cetraxate hydrochloride was due to the unchanged drug, PHPA, or tranexamic acid, studies with aspirin and water immersion -induced gastric ulcers in rats were performed. As a result, it was found that tranexamic acid had an anti-ulcer action similar to that of cetraxate hydrochloride. PMID- 4029809 TI - [Effect of tritoqualine on liver regeneration after partial hepatectomy in rats]. AB - Effect of tritoqualine (TRQ) on liver regeneration after partial hepatectomy in normal rats and chronically injured rats treated with carbon tetrachloride (CCl4) for 12 weeks were investigated by the measurement of serum and liver biochemical parameters concerning the hepatic function. The results are as follows: 1) In normal rats, the liver regeneration rate after partial hepatectomy was increased dose-dependently with the administration of TRQ for 7 days after the operation. TRQ improved BSP retention rate which was decreased after partial hepatectomy. In addition, protein synthetic activity in the liver microsomes prepared from TRQ administered rats was higher than that prepared from control rats, and the contents of serum total protein, serum albumin and liver protein were also higher in TRQ-administered rats. 2) In the rats treated with CCl4 for 12 weeks, the liver regeneration rate after partial hepatectomy was increased dose-dependently with the administration of TRQ for 6 days. TRQ also improved the contents of serum total protein, serum albumin and liver protein. Though the amount of collagen in the liver chronically injured by CCl4 increased more than twice compared with that in the normal liver, the amount of collagen in the regenerating liver of CCl4-treated rats whose liver regeneration was accelerated by TRQ was not different from that in the normal liver. These results suggest that TRQ has the effect of improving the various hepatic functions through the activation of the protein synthesis in hepatocytes. PMID- 4029810 TI - [Anti-inflammatory activity of the dry distillation tar of delipidated soybean (Glyteer) (1)]. AB - The anti-inflammatory activity of the dry distillation tar of delipidated soybean (GL, 0.1 approximately 10%) was investigated by its topical application to mice, rats and guinea pigs; and the effects were compared with those of betamethasone 17-valerate (BV, 0.12%), ibuprofen (IP, 5%), phenylbutazone (PB, 5%) and flufenamic acid (FA, 5%), which were all prepared with the same ointment base. GL (1 approximately 10%) showed a concentration-dependent inhibition of the increased vascular permeability induced by histamine and bradykinin in guinea pigs. GL significantly inhibited rat paw edema induced by carrageenin, but in serotonin-induced paw edema, GL showed only a weak effect. GL also inhibited the erythema formation induced by ultra-violet rays, and the activity was equal to that of PB. The inhibitory potency of GL against the erythema formation induced by arachidonic acid in guinea pigs was equal to that of IP. It is suggested from these results that the mode of action of GL is similar to that of other acidic non-steroidal anti-inflammatory drugs. However, GL did not inhibit paper disk granuloma in rats. Furthermore, GL markedly inhibited the delayed-type hypersensitivity induced by picryl chloride, and the activity was stronger than that of IB, PB and FA. Here GL showed the mode of action seen with steroidal anti inflammatory drugs. The present data provide evidence that GL applied externally possesses a potent effect as an anti-inflammatory drug. PMID- 4029811 TI - [Studies on anti-inflammatory agents. (5). Specific characteristic of bone changes in adjuvant arthritic rats with passage of time]. AB - Adjuvant arthritic rats develop marked changes in the distal limb joints. These changes were observed by soft X-ray photography at appropriate intervals. It was confirmed that the "cotton wool appearance" surrounding the bones, which was readily discernible from the radiographs, was a good indicator for following the progression of bone damages. Standard radiographs were selected to represent the various bone changes based on the "cotton wool appearance". When the incidence rates of bone deformation confirmed on the basis of the above method were plotted against Weibull Probability Paper, the plots conformed with the Weibull distribution function. Thus, it was possible to evaluate bone changes in adjuvant arthritic rats by observing the "cotton wool appearance" surrounding the bones. PMID- 4029812 TI - [Effect of KC-404 on experimental cerebral infarction in rats]. AB - Experimental cerebral infarction accompanying altered cerebral energy metabolism and cerebral edema was produced in rats by injecting arachidonate into the left carotid artery. In the present study, the effects of 3-isobutyryl-2 isopropylpyrazolo [1,5-alpha]pyridine (KC-404) on these ischemic insults as well as on the regional cerebral blood flow (r-CBF) were studied. 1) Cerebral metabolism: On the 7th day of infarction, a significant decrease in ATP content and an increase in glucose content were observed, especially in the left hemisphere. There were no significant changes in lactate and pyruvate contents as compared with normal rat brain. Treatment with KC-404 (10 mg/kg, p.o.) once on the 7th day or twice on the 6th and 7th days of infarction caused a significant increase in ATP content and a decrease in lactate content. Increased content of glucose tended to be suppressed by KC-404. In normal rats, KC-404 (10 mg/kg, p.o.) caused slight but significant increases in cerebral ATP, glucose and pyruvate contents. 2) Cerebral edema: On the 4th day of infarction, significant increases in water content and Na+/K+ ratio and a decrease in K+ content were observed in the left hemisphere. Treatment with KC-404 (10 mg/kg, p.o.) for three preceding days showed a significant suppression of increased water content with a tendency to improve altered electrolyte levels. 3) r-CBF: KC-404 (0.05 mg/kg/min) infused i.v. for 15 min increased more markedly the r-CBF in the affected left hemisphere as compared with that in normal brain.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4029813 TI - [Effects of gefarnate on acute gastric lesions in rats]. AB - The effects of gefarnate on several acute gastric lesions were studied in rats. Gefarnate, given at either 100 approximately 1000 mg/kg orally or intraduodenally, dose-dependently inhibited the formation of gastric lesions induced by HCl-ethanol, HCl-taurocholate and aspirin. Cimetidine, given at 30 approximately 100 mg/kg as a reference drug, also significantly inhibited both HCl-ethanol and aspirin-induced lesions. The present study suggests that gefarnate, as well as cimetidine, is useful for the treatment of acute gastric lesions in man. PMID- 4029814 TI - [Effects of serial administration of vanillyl n-nonoylamide on vocalization responses by arterial algogenics in guinea pigs]. AB - Desensitizing effects of vanillyl n-nonoylamide, one of the synthetic capsaicinoids, were investigated by algogenics induced vocalization in conscious guinea pigs. Intra-arterial administration of bradykinin, acetylcholine and capsaicinoids (capsaicin, dihydrocapsaicin, vanillyl n-nonoylamide) evoked strong vocalization responses. Increasing doses (50 mg/kg, 100 mg/kg, 200 mg/kg, 400 mg/kg) of vanillyl n-nonoylamide were given to guinea pigs by subcutaneous administration for 4 days. Consecutive administration of vanillyl n-nonoylamide produced a weak but not significant desensitizing effect on bradykinin, acetylcholine-evoked vocalization at several doses. However, a complete suppressive effect on capsaicinoids-evoked response was observed in animals treated with serial administration of vanillyl n-nonoylamide. A weak vocalization response reappeared by three kinds of capsaicinoids (3 micrograms), but there were statistically significant effects on vocalization count when compared with the control values. It was therefore concluded that serial administration of vanillyl n-nonoylamide had a selective desensitizing action on chemonociceptors. PMID- 4029815 TI - [Effect of MCI-2016 (bifemelane hydrochloride) on cerebral ischemia following ligation of both common carotid arteries in Mongolian gerbils]. AB - Cerebral protective effect of MCI-2016 and influence of age on survival time in the cerebral ischemic model induced by bilateral-carotid-arterial ligation in male Mongolian gerbils were studied. Of all animals (6 to 40 weeks old), the mean survival time of the immature group (6 to 7 weeks) was long (3.6 hr), but variable, and that of the 10 to 40 weeks group was relatively stable (1.9-2.4 hr), but that of the older group (30-40 weeks) inclined to be reduced. Effects of drugs on this model were studied in 10 to 15 weeks old male Mongolian gerbils. The mean survival time in the control groups was 2.3-2.4 hr. After a single administration of MCI-2016 at doses of 25 mg/kg, i.p., and 100 mg/kg, p.o., the mean survival time were 8.1 and 6.4 hr, respectively. In these cases, some animals survived over 12 hr, while no animals surviving over 12 hr were observed in the control group. In this model, animals showed severe neurological symptoms. This, however, tended to be depressed by the administration of MCI-2016 at a dose of 25 mg/kg, i.p., which was observed early after ligation. A cerebral metabolic activator, Ca-hopantenate, slightly increased the survival time at a dose of 100 mg/kg, i.p., and a cerebral vasodilator, ifenprodil, was not effective. Subsequently, consecutive administration of MCI-2016 at a dose of 25 and 50 mg/kg, p.o., was more effective than a single administration of MCI-2016 at each dose. The mechanism for the cerebral protective effect of MCI-2016 was discussed. PMID- 4029816 TI - Enhancement of bacitracin biosynthesis by branched-chain amino acids in a regulatory mutant of Bacillus licheniformis. AB - DL-4-Azaleucine-resistant mutant of Bacillus licheniformis azlr-1 isolated after N-methyl-N'-nitro-N-nitrosoguanidine mutagenesis, was a better bacitracin producer than the parent strain. In the minimal medium, the antibiotic biosynthesis was 4 times higher in the mutant than in the parent strain and less dependent on L-leucine addition. In the complex fermentation medium, the yield was 18-20% higher in the mutant strain. Transaminase B activity measured in the crude extract revealed that the branched-chain amino acid biosynthetic enzymes were 5-10 times derepressed supplying bacitracin synthetase with enhanced quantity of isoleucine and leucine, the building units of bacitracin molecule. PMID- 4029817 TI - Fungicidal action and structure correlation of monosubstituted phenyl isothiocyanates. AB - The fungicidal activity of 10 monosubstituted phenyl isothiocyanates was observed with four plant pathogens. The ortho- and meta-substituted derivatives possessed a fair activity while the para-substituted ones proved to be highly fungicidal when compared to the control Agrosan GN. PMID- 4029818 TI - The effect of bilirubin on the Fc receptor expression and phagocytic activity of mouse peritoneal macrophages. AB - The effect of bilirubin on the phagocytic activity of mouse peritoneal macrophages and on the expression of Fc receptors and receptors for SRBC was studied. Intraperitoneally administered bilirubin influenced the expression of Fc receptors for IgM, IgG2B, IgA and IgE, whereas the expression of other receptors as well as the phagocytic activity of peritoneal macrophages remained unchanged. The possible mechanism of the effect of bilirubin on Fc receptors is discussed. PMID- 4029819 TI - The origin of tubulovesicular structures in the damaged non-myelinated axon. PMID- 4029820 TI - Observations on the histology of the alimentary tract of Thais bufo (Lamarck) (Neogastropoda: Muricidae). PMID- 4029821 TI - Studies of a new land planarian, Orthodemus indica sp. nov. PMID- 4029822 TI - Changes in the structure and distribution of the Golgi apparatus in guinea pig liver cells in histamine-induced shock. PMID- 4029823 TI - Innervation of the pancreatic blood vessels of the Bulgarian rabbit as revealed by the cholinesterase technique. PMID- 4029824 TI - The epithalamus and dorsal thalamus of three freshwater teleostean fishes. PMID- 4029825 TI - Ultrastructural development of the Herbst corpuscles in the skin of the beak of the domestic duck (Anas platyrhynchos, f. domestica). PMID- 4029826 TI - Postembryonic development of the dorsal vessel in Udumbaria nainiensis Grover (Cecidomyiidae: Diptera). PMID- 4029827 TI - Quantitative study of the supraoptic and paraventricular nuclei of the hedgehog in two different physiological situations. PMID- 4029828 TI - Histology of the intrapulmonary veins in the albino Wistar rat, with special references to the pulmonary myocardium. PMID- 4029829 TI - Morphogenesis and comparative morphology of the nasal apparatus in the swallow (Hirundo rustica L.) (morphogenesis of the nasal capsule, the epithelial nasal tube and the organ of Jacobson in Sauropsida XV). PMID- 4029830 TI - On a few embryonic structures forming evolutionary connections between the two Sauropsida classes (morphogenesis of the nasal capsule, the epithelial nasal tube and the organ of Jacobson in Sauropsida XVI). PMID- 4029831 TI - Teratogenic interactions of consecutively administered cortisone and cyclophosphamide. PMID- 4029832 TI - Excretion of nitrates and nitrites in saliva and bile in the dog. AB - The kinetics of salivary and biliary excretion of inorganic nitrates and nitrites was studied in mongrel dogs after iv injection of these compounds labelled with 15N. There was strong salivary excretion of 15NO-3 after injection of Na15NO3 but little or no nitrites were excreted in the saliva, indicating that the nitrites present in the mouth are mainly the result of in situ transformation of nitrates into nitrites. In the bile, large quantities of nitrates were excreted when the dogs received 15NO-2, indicating endogenous oxidation of the nitrite. PMID- 4029833 TI - Enhancement of hepatocellular genotoxicity of several mutagens from amino acid pyrolysates and broiled foods following ethanol pretreatment. AB - The effect of subchronic ethanol ingestion on the genotoxicity and metabolism of the mutagens 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole (Trp-P-1), 3-amino-1 methyl-5H-pyrido[4,5-b]indole (Trp-P-2), 2-amino-6-methyldipyrido[1,2-a:3',2' d]imidazole (Glu-P-1), 2-aminodipyrido[1,2-a:3',2'-d]imidazole (Glu-P-2), 2-amino 3-methylimidazo[4,5-f]quinoline (IQ) and 2-amino-3,4- dimethylimidazo[4,5 f]quinoline (MeIQ) was evaluated in primary cultures of rat hepatocytes. Male Sprague-Dawley rats were pair-fed, for 8 days, liquid diets containing either ethanol (8%, v/v) or an isocaloric sucrose solution. Ethanol pretreatment significantly (P less than 0.05, Student's t test) enhanced the level of DNA repair stimulated by Glu-P-1, Glu-P-2, IQ and MeIQ. Statistically significant increases in DNA-repair activity ranged from 1.9-fold for IQ to 3.4-fold for Glu P-2. Following a 16-hr exposure, the concentration of parent mutagen in the culture medium decreased by 75-98%. Neither the rate of mutagen metabolism in hepatocyte cultures nor the extent of mutagenic activation in microsome preparations was appreciably affected by ethanol pretreatment. The results suggest that ethanol pretreatment enhances the genotoxicity of Glu-P-1, Glu-P-2, IQ and MeIQ by inducing non-microsomal activation processes. PMID- 4029834 TI - Lack of evidence of carcinogenicity of technical-grade piperonyl butoxide in F344 rats: selective induction of ileocaecal ulcers. AB - The carcinogenicity of technical-grade piperonyl butoxide was studied in F344/DuCrj rats fed a dietary level of 0.5 or 1% for 2 yr. Various tumours were detected in all groups, including the untreated control group, but no significant dose-related increase in the incidence of any tumour was found. Thus, it is concluded that under these experimental conditions piperonyl butoxide was not carcinogenic in F344 rats. Unexpectedly, however, ileocaecal ulcers were found in animals of both sexes in both experimental groups and the incidence was dose related. Further studies are required to establish the mechanism of induction of ileocaecal ulcers by piperonyl butoxide. PMID- 4029835 TI - A device for irradiating guinea-pig skin with ultraviolet light. AB - Animal methodology for investigating photosensitization is of interest because of the potential of some photodynamic chemicals to produce adverse skin reactions. A system has been developed that provides procedural flexibility and the ability to standardize individual guinea-pig exposures to ultraviolet light (UVA and UVB). It consists of a non-stressful restraining method that also protects the animals' eyes from the harmful effects of UV light while allowing reproducible exposure of the backs of the guinea-pigs. The procedure is described in detail and the qualitative and quantitative aspects of the system are presented. In addition, some quantitative aspects of the phototoxic variation in response to 8 methoxypsoralen are investigated. PMID- 4029836 TI - Use of the occlusive patch to evaluate the photosensitive properties of chemicals in guinea-pigs. AB - Guinea-pig tests were conducted on a known photocontact allergen, tetrachlorosalicylanilide (TCSA), a known phototoxin, 8-methoxypsoralen, two reportedly weak photoallergens, musk ambrette and 6-methylcoumarin, and a negative control, octylphenoxy polyethoxyethanol (Triton X-15). The data show that under the test conditions used, photosensitivity responses can be produced, and combinations of these as well as the other biological responses can be readily defined. The results indicate that musk ambrette is photoallergenic, that 8-methoxypsoralen is phototoxic and that Triton X-15 is only a slight irritant. On the other hand, results with TCSA suggest that it is a strong contact allergen and photoallergen, while 6-methylcoumarin would be considered to be a weak contact allergen with weak phototoxic properties. Previous reports that barrier destruction or adjuvanticity is necessary to produce photoallergy to musk ambrette were not confirmed; by ensuring occlusion using standard methods, the photoallergic nature of the response to this material was clearly demonstrated. A device described elsewhere (Newmann & Parker, Fd Chem. Toxic. 1985, 23, 683) has made it possible to develop methods that can be used to differentiate clearly among the possible biological responses that can occur in guinea-pigs when photoreactive materials are applied to their skin and irradiated. The probable biological responses that need to be defined, under the above conditions, are primary irritation, delayed contact hypersensitivity, phototoxicity and/or photoallergenicity. PMID- 4029838 TI - [In vitro histomechanical studies of the tunica conjunctiva bulbi]. PMID- 4029837 TI - Formation of nitrosoiminodialkanoic acids during the nitrosation of peptides. AB - The nitrosation of dipeptides by nitrous acid in aqueous medium leads to a rearrangement, the products being N-nitrosoiminodialkanoic acids. Such reactions are likely to occur in gastric juice. PMID- 4029839 TI - [Deposition of 3H-8-MOP in the eye and skin by PUVA therapy]. PMID- 4029840 TI - [Life expectancy following operations for senile cataract]. PMID- 4029841 TI - [Lens opacities following intravitreous silicone injection]. PMID- 4029842 TI - [Postoperative cataract formation following extracapsular cataract extraction- with and without lens implantation]. PMID- 4029843 TI - [Clinical corneal problems in cataract operation]. PMID- 4029844 TI - [Intraoperative complications in phacoemulsification--analysis and initial results]. PMID- 4029845 TI - [Endothelial cell defects caused by ultrasound phacoemulsification in a model]. PMID- 4029846 TI - [Excision of the posterior lens capsule with preservation of the anterior vitreous face]. PMID- 4029847 TI - [Personal 32-year experience with cataract operations]. PMID- 4029848 TI - A retrospective study of the classical operation of complicated cataract in comparison with pars-plana approach. PMID- 4029849 TI - [Thermal epithelial abrasion in iris prolapse of long duration following cataract extraction]. PMID- 4029850 TI - [Optimal construction of retropupillary artificial lenses in relation to the use of the YAG laser]. PMID- 4029851 TI - [Implantation of a modified Dubroff 3-loop anterior chamber lens]. PMID- 4029852 TI - [Corneal endothelial findings following silicone oil implantation--initial experiences]. PMID- 4029853 TI - [Ridge-shaped, retrocorneal connective tissue membrane in corneal ulcer]. PMID- 4029854 TI - [Isovolemic hemodilution in patients with retinal branch vein occlusion]. PMID- 4029855 TI - [Electrophysiologic studies of patients with diabetic retinopathy]. PMID- 4029856 TI - [Electrophysiologic verification of amaurosis fugax]. PMID- 4029857 TI - [Pattern ERG and pattern visually evoked cortical potentials in autosomal dominant infantile optic atrophy]. PMID- 4029858 TI - [ERG in embolism of the central retinal artery]. PMID- 4029859 TI - [Effect of staged monocular masking on the intensity of nystagmus in latent nystagmus]. PMID- 4029861 TI - [Acupuncture in migraine]. PMID- 4029860 TI - [Hypnosis in the treatment of migraine and headache]. PMID- 4029862 TI - [Acute pancreatitis. Risk predictors and the role of phospholipase A]. PMID- 4029864 TI - [Improvement of work organization and information flow in medical practice. Proposal of a solution for communication problems between physician, physician's assistant and patient]. PMID- 4029863 TI - [Careful treatment of hypertension in the elderly. A multicenter medical practice study with Ergodesit Spezial]. PMID- 4029865 TI - [Immunosuppression in juvenile diabetes mellitus? Critical viewpoint on the treatment with cyclosporin A with consideration of the differential etiology]. PMID- 4029866 TI - [ The effect of coffee on the motor function of the gallbladder]. PMID- 4029867 TI - [Treatment of secondary synovitis. Double blind study of proglumetacin versus indomethacin]. PMID- 4029868 TI - [Predictors of further suicidal behavior in hospitalized patients following a suicide attempt. Literature review]. AB - In a review of 70 follow-up studies of patients hospitalised after attempted suicide, those follow-up studies were listed which tried to find predictors of further suicidal behaviour by statistical methods. The following predictors for patients with attempted suicide hospitalised in different institutions were found: "Previous attempted suicide" (risk of repetition of attempted suicide as well as of suicide), "previous psychiatric treatment" (risk of repeated attempted suicide), addiction (suicide or repetition of attempted suicide), personality disorder (repetition of attempted suicide), old age and male sex (suicide). There is only small evidence for the predictive power of other variables. Possibilities of improving the prognosis of suicide attempts are discussed. PMID- 4029869 TI - [Clinical aspects and diagnosis of acoustic neurinomas]. AB - The application of microsurgical techniques for the removal of acoustic neuromas has evidenced greatly improved postoperative results. Therefore the early detection of an acoustic neuroma is a special need for every neurologist. The development of new electrophysiological and radiological procedures now allows a far better approach in the diagnosis of acoustic neuromas. Brain stem auditory evoked potentials as well as acoustic reflex testing have shown to be rather sensitive tools in the diagnosis of retrocochlear pathology. Other electrophysiological procedures have been widely replaced by these techniques. Gasmeatocisternography in combination with cranial computed tomography is the method of choice in the detection of small acoustic neuromas. The current status in the application of different techniques for the diagnosis of acoustic neuromas is reviewed. PMID- 4029870 TI - [Thalamic dementia]. AB - Report with complementary clinical examinations and detailed neuropathological findings of a case of subacute progressing "thalamic dementia", interpreted as combined systemic degeneration of the dorsal and medial thalamic nuclei. For the development of the EEG changes, which were followed from beginning of the disease, a slowly advancing reduction of the function of the meso-diencephalic activating system proved responsible. The inferior olives were symmetrically atrophied and the fasciculus tegmenti centralis was on both sides completely degenerated. It is to be considered that the inferior olives are directly subordinated to the medial thalamic nuclei by the way of the fasciculus tegmenti centralis. In the cerebellum nerve cell groups and fiber bundles, which are closely connected with the reticular system, are degenerated. The systemic medial degenerations of the thalamus belong to the abiotrophies in the sense of Gowers original conception. PMID- 4029871 TI - Interaction of troponin C and calmodulin with troponin I and troponin T. An electrophoretic study. PMID- 4029872 TI - The role of calmodulin in the ATP-dependent Ca2+-uptake by dog brain microsomes. PMID- 4029873 TI - Potential occurrence of calcium bilirubinate stone after gastrectomy. PMID- 4029874 TI - Production of corticosterone in male homozygous Brattleboro rats. AB - Plasma concentration, metabolic clearance rate and in vitro adrenal production of corticosterone were measured in Brattleboro male rats homozygous for diabetes insipidus (DI) and in Long-Evans male rats (LE) as controls in resting conditions, under stress caused by pentobarbitone anesthesia and surgery and after three days water deprivation. In resting animals, plasma concentrations and in vitro adrenal production of corticosterone were higher in DI rats than in LE rats. Under pentobarbitone anesthesia and surgery, plasma concentrations and metabolic clearance rate of corticosterone were slightly but not statistically lower in DI rats; however, the in vivo production rate of corticosterone was significantly lower. After three days water deprivation, increasing plasma corticosterone level was consistently higher in DI than in Le rats. These results are not in favour of a reduced glucocorticoid activity of the adrenal of DI rats and of an important role played by vasopressin on the stimulation of the hypothalamopituitary adrenal activity at least in resting conditions; its role may depend upon stressful circumstances. PMID- 4029875 TI - Stimulatory effect of calcitonin on fatty acid synthesis in the liver of fed rats. AB - The effect of calcitonin (CT) on free fatty acid concentration in the serum and liver of fed rats was investigated. A single subcutaneous administration of CT (synthetic [Asu1,7] eel CT;80 MRC mu/100 g body weight) produced a significant increase in serum free fatty acid concentration. An appreciable effect of CT was observed at a dose of 5 MRC mU/100 g body weight. The hormonal effect was also observed in thyroparathyroidectomized rats. The effect of CT on serum free fatty acid was diminished by fasting. Free fatty acid content in the hepatic cytosol of fed rats was markedly increased by CT administration. The hormonal effect was observed at a dose of 5 MRC mU/100 g body weight. Furthermore, stimulation of fatty acid synthesis caused by intraperitoneal injection of alanine (1.122 mmoles/100 g body weight) was markedly enhanced by administration of CT (5, 20 and 80 MRC mU/100 g body weight). This effect of CT on the liver may be the cause of increased level of fatty acid in the serum. The present results suggest that CT may stimulate synthesis of free fatty acid in the liver of fed rats. PMID- 4029876 TI - Red cell sorbitol and diabetic control. AB - There is a disagreement about the value of red cell sorbitol as an indicator of diabetic control. We studied 7 insulin requiring diabetics, one for 10 days and 6 for 24 hours. In the 10-day study, blood samples were obtained every 4-6 hours. Sequential analysis of plasma glucose and red cell sorbitol levels showed that simultaneous levels had the best correlation r = 0.534, P less than .001. In the 24-hour studies, blood samples were obtained at 1 to 4-hour intervals. Three of the 6 patients showed the best correlation between simultaneous plasma glucose and red cell sorbitol, with r = 0.727 to 0.957 and P less than .001 to P less than .07. When plasma glucose values were compared to red cell sorbitol levels 1, 2, 4, 8 and 12 h later, correlation coefficients were not as good as the simultaneous comparison. We conclude that the measurement of red cell sorbitol correlates well with simultaneous plasma glucose in some but not all diabetic subjects and provides no additional information to the clinician. PMID- 4029877 TI - Therapy of endemic goitre: controlled study on the effect of iodine and thyroxine. AB - Two kinds of medical treatment of endemic goitre (400 microgram of iodine, n=11, and 150 microgram of L-thyroxine, n=12) were compared in a double blind study with a placebo group (n=12) during a period of 12 months and an observation time of three months after cessation of therapy. The means of the neck circumference and of the estimated thyroid volume decreased significantly during treatment in both groups, whereas no significant difference was observed in the placebo group. The results in both therapy groups did not differ significantly from each other. No side effects or symptoms of hyperthyroidism were observed. During treatment the index of free thyroxine (FT4I) increased significantly in both the iodine and the thyroxine group and delta TSH after TRH decreased significantly. Total triiodothyronine (TT3) did not show significant alterations. Three months after cessation of therapy in the thyroxine treated group the mean FT4I dropped into the range before treatment, whereas it remained slightly elevated in the iodine group. In the thyroxine treated group the mean delta TSH was higher than its value before therapy. After withdrawal of iodine, however, the mean delta TSH remained decreased for three months. The study indicates that 400 micrograms of iodine per day may be at least as effective as a standard dose of 150 micrograms of thyroxine to treat endemic goitre in an iodine deficient area. PMID- 4029878 TI - Urinary kinetics of triiodothyronine and their modification with aging. AB - The urinary kinetics of triiodothyronine (T3) in healthy young and old people has been studied. The behavior of urinary excretion is similar in both age groups, expressed in our mathematical model in the cumulative kinetics as well as in the urinary rate. However, a significant decrease (P less than 0.025) of renal clearance of T3 in elderly individuals has been found. No significant differences (P greater than 0.05) were observed in any other kinetic parameters. The possible influence of the reduction of glomerular filtrate has been discussed as the most important pathogenic factor of the decreased renal clearance of this hormone. Possibly, modifications of the distribution volumes are also involved. Due to the limited number of persons studied, for ethical reasons, the results obtained are not definitive. PMID- 4029879 TI - Free thyroxine measurement by one-step method in the plasma of treated and untreated hypothyroid infants. AB - The one-step radioimmunoassay of free thyroxine (f-T4) using a gamma-coated kit was used in this study. In controls the mean plasma levels (pmol/l) were 20.8 (range 13.5-37) during the first days of life, 17.4 (11.5-27) from 1 week to 1 year, and 17.0 (10-24.5) after 1 year. In preterm newborns it was correlated with the length of gestation. Among 23 untreated hypothyroid infants aged 15-22 days, f-T4 was undetectable in those with athyreosis, while in cases with dysgenetic thyroid it was variable, correlated to the width of the gland (r = 0.77, p less than 0.01). In 44 hypothyroid patients treated with l-T4, a highly significant positive correlation was found after the 1st month of treatment between plasma f T4 and the daily l-T4 dose (r = 0.46, p less than 0.01), and a negative one between f-T4 and plasma TSH (r = -0.59, p less than 0.001). It is concluded that measurement of f-T4 offers a valuable means for control of diagnosis and treatment in congenital hypothyroidism, especially useful for avoiding both under and overtreatment. Its correlations suggest that it is the most reliable hormonal measurement in the follow-up of thyroid children. PMID- 4029880 TI - Asymptomatic primary empty sella in a 14-year-old girl: comparison of computer tomography and nuclear magnetic resonance imaging. AB - An enlarged, balloon-shaped sella was detected by chance in a completely asymptomatic 14-year-old girl, who presented with tall stature. While all endocrine functions were found to be normal, metrizamide cisternography with computer tomography revealed a flattened pituitary at the bottom of an empty sella. This could be compared later with nuclear magnetic resonance tomography, thus avoiding intrathecal contrast material and radiation exposure for the patient. The new technique depicts the sellar contents very well. PMID- 4029881 TI - Final stature in brain tumours other than craniopharyngioma: effect of growth hormone. AB - The final growth pattern of 27 children who developed growth hormone deficiency after treatment of an intracranial tumour other than craniopharyngioma was assessed retrospectively. No patient achieved his or her genetic potential, though 12 attained an adult height above the the third centile for the population. All patients showed a tendency to a eunuchoid body build irrespective of whether puberty was spontaneous or not. PMID- 4029882 TI - Delayed puberty and hypoplastic uterus associated with hyperprolactinemia: successful treatment with bromocriptine. AB - A 15-year-old girl referred because of primary amenorrhea was found to have a hypoplastic uterus and persistent hyperprolactinemia (72-110 ng/ml). The gonadotrophin-dependent pubertal signs, i.e. breast and vulvar development, were significantly retarded (Tanner stage 2-3) while sexual hair was well developed; bone age was 13 years. The endocrinological evaluation revealed gonadotrophin secretion (LH-basal: 0.85-1.25; peak after LH-RH: 10.4 mIU/ml; FSH-basal: 1.63 2.5; peak: 8.2 mIU/ml) and E2 levels (26-68 pg/ml) which were appropriate for Tanner stage 3. The high basal levels of PRL were nonresponsive to either stimulatory (TRH) or inhibitory (nomifensine) agents. CT scan of the brain suggested the presence of a pituitary microadenoma. Following therapy with bromocriptine (2.5 mg/day) plasma PRL levels dropped to normal (5-6.8 ng/ml) with an accompanying catch-up of pubertal development and linear growth and a marked increase in size of the uterus as documented by repeated ultrasonographic examinations. Menarche occurred 5 months after initiation of therapy, followed by regular menses thereafter. Repeated CT scan of the brain showed a decrease in the density and size of the still persisting lesion. This patient demonstrates that hyperprolactinemia can cause delayed puberty with a particular inhibitory effect on uterine growth and development. PMID- 4029883 TI - Precocious puberty secondary to cranial irradiation for tumors distant from the hypothalamo-pituitary area. AB - This retrospective study is the first report of the occurrence of central precocious puberty in 6 children having received cranial irradiation. Pubertal development took place at a mean age of 7 5/12 years (6 10/12-7 10/12 years in 5 girls and at 9 years in 1 boy). They had received 2,400-4,500 rad at a mean age of 5 2/12 years. In addition, 5 children had GH deficiency so that their growth spurt was blunted and 3 of them were left with an extremely short stature. This condition would require a therapeutic approach combining the use of an LHRH analogue and hGH therapy when necessary in order to protect from too rapidly progressing bone maturation. PMID- 4029884 TI - Increased peripheral aromatase activity in prepubertal children with partial androgen insensitivity syndrome. AB - It has been suggested that rate of estrogen formation was higher in patients with androgen insensitivity syndrome (AIS). This work was designed to find out if peripheral aromatase activity could be related to a defect in androgen action in prepubertal children with male pseudohermaphroditism. Fibroblast estrogen production was assayed by a highly specific enzymatic determination. Foreskin fibroblast strains were raised from 17 children with partial androgen insensitivity (PAIS) as defined by dihydrotestosterone binding activity in cells. Results are expressed as pmol estrogens/mg proteins synthetized/day when cultured fibroblasts are incubated with D4-androstenedione. In normal prepubertal boys (n = 19), aromatase activity ranged between 5 and 10 pmol estrogens/mg proteins/day, while in postpubertal boys it varied between 15 and 34 pmol estrogens/mg proteins/day. In prepubertal boys with PAIS (n = 17) aromatase activity is highly elevated: 19.4 +/- 8.4 pmol/mg proteins/day. These results show that (a) peripheral aromatase activity is low before puberty and (b) fibroblast estrogen synthesis is significantly (p less than 0.001) increased in prepubertal children with PAIS. Our data suggest that low utilization of androgens by target cells stimulates the production of estrogen. Peripheral aromatase activity can thus be considered as a 'marker' of androgen insensitivity in prepubertal children with male pseudohermaphroditism. PMID- 4029885 TI - Analysis of androgen-5 alpha-reductase by an enzyme kinetic method. AB - Analysis of androgen-5 alpha-reductase (A-5 alpha-R) is commonly done by measuring distinct testosterone (T) metabolites after tissue incubation. In the present study, A-5 alpha-R analysis was performed according to the principles of Michaelis-Menten, i.e. by evaluation of KM and Vmax data of the enzyme. 48 tissue samples (foreskin) of healthy boys in the age group 6 months to 8 years were examined. Incubation was carried out using increasing concentrations of 3H-T (8 208 nM) as substrate, followed by extraction and thin layer chromatography (TLC) of the reaction products. Zone detection and quantitation of radioactivity was done by a computing TLC scanner. The specific radioactivity of the metabolites was evaluated by high resolution radio gas chromatography. KM values ranged from 81.8 to 118.1 nM and Vmax from 8.9 to 30.1 pmol/mg . h. Coefficient of variation was smaller for KM (0.1) than for Vmax (0.38). It is recommended to do A-5 alpha R analysis by evaluation of the enzyme kinetics as this is a reproducible method giving accurate biochemical data of the qualitative and quantitative characteristics of the enzyme. PMID- 4029886 TI - Transferrin metabolism in alcoholic liver disease. AB - The metabolism of transferrin was studied using purified 125I-labeled transferrin in 11 alcoholic patients; six with fatty liver and five with cirrhosis. Six healthy subjects whose alcohol intake was les than 40 gm daily were studied as a control group. There were no significant differences in the mean fractional catabolic rate and plasma volume in the alcoholic groups when compared with control subjects. A significantly decreased mean serum transferrin concentration was found in the alcoholic cirrhotic patients (1.8 +/- 0.3 gm per liter vs. 2.9 +/- 0.2; p less than 0.01), resulting from diminished total body synthesis (0.9 +/- 0.2 mg per kg per hr vs. 1.8 +/- 0.2; p less than 0.01). In contrast, in the patients with alcoholic fatty liver, the mean total body transferrin synthesis (2.4 +/- 0.3 mg per kg per hr) was significantly increased when compared with controls (p less than 0.05). For all the alcoholic patients, the serum transferrin correlated with transferrin synthesis (r = + 0.70; p less than 0.01) but the serum iron did not. These results suggest that, in alcoholic cirrhosis, transferrin synthesis is decreased, probably reflecting diminished synthetic capacity by the liver. In contrast, in patients with alcoholic fatty liver, transferrin turnover is accelerated. PMID- 4029887 TI - Drug-induced hepatitis associated with anticytoplasmic organelle autoantibodies. AB - A study from five hepatology units documenting 157 cases of drug-induced hepatitis and a second study from a laboratory of immunology which tested more than 100,000 sera permitted us to establish the frequency of antiorganelle antibodies and their diagnostic value in drug-induced hepatitis. In drug-induced hepatitis caused by a heterogenous group of drugs consisting of ajmaline, aminopterine, isaxonine, isoniazid, perhexiline, phenylbutazone and troleandromycine, antiorganelle antibodies were absent or rare. In drug-induced hepatitis caused by another heterogenous group of drugs, including clometacin, fenofibrate, oxyphenisatin and papaverine, antismooth muscle, antinucleus and antimitochondria antibodies were found in isolation or in different combinations in 70% of cases. From the presence of antismooth muscle antibodies in sera, we could trace 30 cases of clometacin-induced hepatitis. The third group included drug-induced hepatitis with special antibody:iproniazid-induced hepatitis with antimitochondrial antibody 6 and tienilic acid (ticrynafen)-induced hepatitis with antiliver/kidney microsome antibody 2 (anti-LKM2). These two antibodies are rare in routine sera and were absent in patients who received the drug and had no liver damage. From the presence of corresponding antibodies, we detected six cases of iproniazid-induced hepatitis and 67 cases of tienilic acid-induced hepatitis. Antiorganelle antibodies found in high titers disappeared in 2 to 24 months following withdrawal of the offending drug. The fourth group was represented by halothane-induced hepatitis; antiliver/kidney microsome antibody 1 was weak and infrequent. Similarities between drug-induced hepatitis of the second group and lupoid hepatitis suggest that drugs may reveal this spontaneous disorder.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4029888 TI - Changes of hepatitis B virus DNA in liver and serum caused by recombinant leukocyte interferon treatment: analysis of intrahepatic replicative hepatitis B virus DNA. AB - Twenty patients with HBeAg-positive chronic liver disease were given large doses of recombinant leukocyte interferon for 4 weeks. Changes of hepatitis B virus DNA in livers and sera were analyzed by the molecular hybridization technique in paired biopsies obtained before and 2 weeks after treatment. Serum hepatitis B virus DNA was examined before, during and after the treatment until 4 weeks post interferon. Analysis of hepatic hepatitis B virus DNA revealed species that appeared to represent various forms of replicative hepatitis B virus DNA, i.e., relaxed circular, linear, supercoiled and single-stranded hepatitis B virus DNA, respectively. No evidence of integration of hepatitis B virus DNA in genomic DNA was obtained. Of 15 cases which were positive for hepatic hepatitis B virus DNA before treatment and in which paired biopsies were obtained, hepatic hepatitis B virus DNA became negative in 4, decreased in 5 and unchanged in 6. Among several types of replicative viral DNA in liver tissue, supercoiled hepatitis B virus DNA tended to remain after other forms were reduced. A close correlation between hepatic and serum hepatitis B virus DNA was found in 37 liver biopsy samples and corresponding sera. These results indicate that interferon treatment reduces serum hepatitis B virus levels by inhibiting viral replication in the liver and that persistence or reappearance of hepatitis B virus in serum after interferon is associated with replication. PMID- 4029889 TI - Cell-mediated cytotoxicity of sensitized spleen cells against target liver cells- in vivo and in vitro study with a mouse model of experimental autoimmune hepatitis. AB - Spleen cells obtained from C57BL/6 (B6) mice with an experimental autoimmune hepatitis were transferred to normal C57BL/6 recipient mice. Most prominent liver damages occurred in the recipient mice injected with sensitized nylon wool column adherent spleen cells from the donor mice. Production of such liver damage was blocked by treatment of the sensitized adherent spleen cells with anti-Thy 1,2 monoclonal antibody and complement before injection. Based on these in vivo results, a microcytotoxicity assay was performed using isolated C57BL/6 hepatocytes as target cells and sensitized spleen cells obtained from hepatitis donor mice as effector cells. The fraction of sensitized nylon wool-adherent spleen cells demonstrated a high cytotoxic activity against isolated syngeneic hepatocytes, although the other fractions and spleen cells of control animals showed no such effect. The cytotoxic activity of sensitized-adherent spleen cells against target hepatocytes was significantly reduced after treatment with anti Thy 1,2 antibody and complement, but it increased after depletion of B cells and Fc receptor-bearing T-cells. Although these sensitized nylon wool-adherent spleen cells showed high cytotoxic activities against syngeneic hepatocytes, their cytotoxicity against allogeneic hepatocytes was lower. They exerted no cytotoxic activity against syngeneic renal glomerular cells and EL-4 thymoma cells. These results suggest that sensitized T-cells in the nylon wool column-adherent fraction play the role of cytotoxic killer cells against target liver cells in vitro. PMID- 4029890 TI - Hepatitis B virus DNA, HBeAg and delta infection during the course from acute to chronic hepatitis B virus infection. AB - The presence of hepatitis B virus DNA in serum was determined in 57 unselected patients during the course from acute to chronic hepatitis B infection. Forty-six (81%) patients were hepatitis B virus DNA-positive in the first available serum sample. Generally, hepatitis B virus DNA was cleared before or at the same time as HBeAg, but in two patients (4%), hepatitis B virus DNA could be demonstrated after HBeAg clearance. One of the latter patients had hepatitis B virus DNA in the presence of anti-HBe. Both patients became hepatitis B virus DNA-negative. Seven of the hepatitis B virus DNA-positive patients received long-term treatment with prednisone, and three of them continued to be hepatitis B virus DNA positive for more than 10 years. Among the untreated patients hepatitis B virus DNA could be detected for up to 7 years, and 10 patients were hepatitis B virus DNA positive for three years or more. Twenty-four patients (42%) showed serological signs of delta agent infection. Hepatitis B virus DNA clearance was observed in a significantly higher proportion (87%) of delta-infected patients as compared to patients with no delta infection (45%) (p less than 0.05). In addition patients with delta infection had a significantly increased hepatitis B virus DNA clearance rate as compared to patients without delta markers in their serum (p less than 0.01). In one (8%) delta-infected patient, hepatitis B virus DNA clearance was followed by a fall in transaminases into the normal range as opposed to results in 86% of patients with pure hepatitis B (p less than 0.002). PMID- 4029891 TI - Hepatic mitochondrial oxidative metabolism in rats with chronic dietary iron overload. AB - We examined the effects of chronic dietary iron overload on hepatic mitochondrial oxidative metabolism. Experimental iron overload was produced by feeding rats a chow diet supplemented with carbonyl iron over a 7-week period. Biochemical and histologic evaluations of liver tissue confirmed moderate degrees of hepatic parenchymal iron overload. Electron microscopy showed no abnormalities in hepatic mitochondrial ultrastructure in blocks of tissue or in mitochondrial fractions from iron-loaded liver. Studies of mitochondrial oxidative metabolism revealed a consistent and progressive decrease in state 3 (ADP-stimulated) respiration and in respiratory control ratios at hepatic iron concentrations above 1,000 micrograms per gm for all three substrates studied, glutamate, beta hydroxybutyrate and succinate. Changes in state 4 (ADP-limited) respiration and ADP/O ratios were not progressive with increasing hepatic iron concentrations. At hepatic iron concentrations at which there were decreases in state 3 respiration and respiratory control ratios, there was also evidence of lipid-conjugated diene formation, indicative of mitochondrial lipid peroxidation. There were no changes in mitochondrial function when iron as either ferritin or hemosiderin or as a combination of ferritin, hemosiderin and ferric nitrilotriacetate was added in vitro to normal liver homogenates. Use of density gradient centrifugation to reduce iron and lysosomal contamination of mitochondrial fractions failed to prevent the reduction in mitochondrial function. We conclude that moderate degrees of chronic hepatic iron overload in vivo result in an inhibitory defect in the mitochondrial electron transport chain as evidenced by a decrease in state 3 respiration and respiratory control ratios. PMID- 4029892 TI - Reduced transport of bilirubin and asialoorosomucoid in regenerating rat liver is a microtubule-independent event. AB - In previous studies, we found that uptake of bilirubin and asialoorosomucoid is depressed in regenerating rat liver. To determine what role the hepatic cytoskeleton plays in this modulation of uptake, animals were treated with colchicine, an inhibitor of microtubular polymerization. Normal unoperated rats or rats following two-thirds hepatectomy or sham surgery were injected with colchicine, lumicolchicine (50 micrograms per 100 gm of body weight, i.p.) or normal saline. Lumicolchicine, an analog of colchicine, has no effect on microtubules and was used as a control. At 12 hr after surgery, sham-operated and unoperated animals received a second equal dose. Partially hepatectomized animals received one-third the initial dose. At 24 hr after surgery, livers were perfused in situ and single-pass multiple indicator dilution studies were performed. Colchicine as compared to lumicolchicine pretreatment reduced apparent influx of bilirubin and asialoorosomucoid in regenerating liver by 50% but had no effect in liver from normal or sham-operated rats. Analysis of indicator dilution curves revealed that reduced influx in colchicine-treated liver was attributable to an increased vascular volume of distribution. These results suggest that microtubules may play a role in maintenance of normal hepatic vascular architecture during regeneration. Lack of effect of colchicine on modulation of bilirubin and asialoorosomucoid uptake during regeneration suggests that other, as yet unknown, factors result in down-regulation of the specific hepatocellular transport systems for these two ligands. PMID- 4029893 TI - Measurement of fibrosis in needle liver biopsies: evaluation of a colorimetric method. AB - Collagen content was measured in 38 needle liver biopsies (8 steatosis, 8 chronic hepatitis, 7 fibrosis and 15 cirrhosis) by a new colorimetric method based on the selective capacity of Sirius red and Fast green to bind to collagen and noncollagenous proteins, respectively. The values were compared with those obtained after determination of the degree of fibrosis by morphometry in the same tissue. In biopsies with cirrhosis and fibrosis, there was a higher amount of collagen than in biopsies with chronic hepatitis and steatosis. Furthermore, there was a highly significant direct correlation between the collagen content measured colorimetrically and the degree of fibrosis determined morphometrically (r = 0.77, p less than 0.001), suggesting that this new colorimetric method is useful in measuring the degree of fibrosis in needle liver biopsies. PMID- 4029894 TI - Function of the autonomic nervous system in patients with hepatic encephalopathy. AB - To obtain further pathophysiological details concerning the development of cardiovascular disturbances in severe liver disease, the state of the autonomic nervous system, the function of the baroreceptor reflex pathway and the responsiveness of the cardiovascular system to noradrenaline, angiotensin II and isoprenaline were investigated in 11 patients with hepatic encephalopathy and in 10 healthy control subjects. Increased plasma levels of noradrenaline and adrenaline and an attenuated increase in heart rate in response to atropine were found in patients with hepatic encephalopathy. These changes and the hemodynamic disturbances tended to be more pronounced in patients with hepatic encephalopathy Grades III-IV as compared to hepatic encephalopathy Grades I-II. The increase in systolic blood pressure induced by infusion of noradrenaline (400 ng per kg per min) and angiotensin II (20 ng per kg per min) was higher in the patients than in healthy control subjects (hepatic encephalopathy Grades I-II: p less than 0.001; hepatic encephalopathy Grades III-IV: p less than 0.02). The changes in mean and diastolic blood pressure in response to angiotensin II were more pronounced in hepatic encephalopathy grades I-II than in hepatic encephalopathy Grades III-IV (p less than 0.02). The decrease of heart rate in response to blood pressure increase in patients with hepatic encephalopathy was not different from control subjects except a smaller decrease during angiotensin II infusion in hepatic encephalopathy grades III-IV (p less than 0.05). The responsiveness to isoprenaline was diminished (p less than 0.001). The present results indicate that the increased activity of the sympathetic nervous system in hepatic encephalopathy is associated with decreased parasympathetic tone.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4029895 TI - A randomized comparison of metoclopramide and domperidone on plasma aldosterone concentration and on spironolactone-induced diuresis in ascitic cirrhotic patients. AB - The effect of metoclopramide and domperidone, two dopamine antagonists, administered to cirrhotic patients with ascites and secondary hyperaldosteronism, was examined to evaluate the changes in plasma aldosterone levels and in spironolactone-induced diuresis. In 15 patients with ascites and secondary hyperaldosteronism, the intravenous administration of 10 mg metoclopramide significantly increased plasma aldosterone levels (23%, p less than 0.01). This effect was observed when an equivalent dose of domperidone was administered. In 20 ascitic patients treated with spironolactone (300 mg per day), the administration of metoclopramide (20 mg) significantly reduced urinary output (24%, p less than 0.001) and urinary sodium (35%, p less than 0.001) while simultaneously increasing urinary potassium (24%, p less than 0.001) and plasma aldosterone (40%, p less than 0.001). This effect was not observed with domperidone in an equivalent dose. Therefore, it is recommended that metoclopramide should be avoided during diuretic therapy in cirrhotic patients with ascites. In these circumstances, domperidone is preferred. PMID- 4029896 TI - Polycythemia and the Budd-Chiari syndrome: study of serum erythropoietin and bone marrow erythroid progenitors. AB - The mechanism of polycythemia associated with the Budd-Chiari syndrome is unknown. Erythropoiesis in 10 patients with Budd-Chiari syndrome was studied in an attempt to distinguish prior unrecognized polycythemia vera from secondary polycythemia. Serum erythropoietin was assayed using a mouse fetal liver erythroblast assay. High concentrations of serum erythropoietin were observed in 6 of 7 patients with acute primary Budd-Chiari syndrome. Levels were normal in four patients who were investigated during the chronic phase and were increased in one with persisting polycythemia. In one patient, erythropoietin concentration in the hepatic vein was twice the level measured in peripheral, caval and renal venous blood. Bone marrow erythroid progenitors developed in vitro in the absence of exogenous erythropoietin in all polycythemia vera cases studied in acute and chronic phases, whether polycythemia persisted or not. These findings indicate that hepatic erythropoietin production occurs in the acute phase of Budd-Chiari syndrome and suggest that, in some cases of Budd Chiari syndrome, polycythemia which resolves after the acute phase may be secondary to liver disease. PMID- 4029897 TI - The effect of 3-palmitoyl-(+)-catechin on Kupffer cells in guinea pig liver. AB - We report a morphometric study on the effect of 3-palmitoyl-(+)-catechin on phagocytic activity of latex particles by Kupffer cells in guinea pig liver. We found an increase in the density of latex particles in Kupffer cells of animals treated with 3-palmitoyl-(+)-catechin. The volume and density of Kupffer cells of treated animals increased (p less than 0.01); there was no significant difference in surface density of the plasma membrane. None of the parameters measured was altered in endothelial cells. These results show that 3-palmitoyl-(+)-catechin produces morphological and functional changes in Kupffer cells. PMID- 4029898 TI - Altered thiol and calcium homeostasis in oxidative hepatocellular injury. PMID- 4029899 TI - Transferrin and the alcoholic liver. PMID- 4029900 TI - Induction by drugs of hepatitis and autoantibodies to cell organelles: significance and interpretation. PMID- 4029901 TI - Diagnostic value of different antiliver/kidney microsome antibodies. PMID- 4029902 TI - Culture-negative neurocytic ascites. PMID- 4029903 TI - Mucosal biopsy of vascular ectasia (angiodysplasia) of the large bowel detected during routine colonoscopic examination. AB - Between 1975 and 1983, 9434 colonoscopic examinations were performed at the University Hospital of Zurich. Localized vascular ectasia was detected in 84 patients and there were 48 mucosal biopsies from 46 patients. From the total of 48 biopsies only 24 (50%) showed vascular anomalies. The most frequent lesion encountered was groups of thin-walled dilated vessels in the lamina propria seen in 21 biopsies from 20 patients. These dilated vessels are not specific but in respect of age (median 69 years), location (predominantly in the caecum and the ascending colon) and frequent multiplicity, they are suggestive of angiodysplasia. Five of the 20 patients suffered from chronic anaemia due to haemorrhages. The three other positive biopsies (from two patients) revealed a tiny haemangioma in the sigmoid colon of a 28-year-old woman and a few large, thick-walled probably malformed vessels in the mucosa of the caecum of a 17-year old boy. Twenty-four biopsies did not show any histologically significant vascular anomaly. Mucosal biopsy of vascular lesions detected during routine colonoscopic examination will, if positive, most frequently simply confirm the endoscopically diagnosed vascular ectasia and may in rare cases show or alert suspicion to vascular lesions other than angiodysplasia. Definitive morphological diagnosis will however only rarely be achieved by this method of investigation. PMID- 4029904 TI - Melanocytic dysplasia and melanoma. AB - A review of a series of 226 melanomas, representing 95% of the melanomas presenting in one year, has shown that 34% are associated with atypical melanocytic proliferation or melanocytic dysplasia in the adjacent skin. The dysplasia may be lentiginous, predominantly spindle-celled or non-lentiginous in pattern. These variants appear to correspond to the previously reported lesions, lentiginous and epithelioid melanocytic dysplasia and atypical melanocytic hyperplasia respectively. Some of these are referred to as dysplastic naevi. All these variants were seen in a review of 325 cases of melanocytic dysplasia. The variations are commonly seen within the same lesion and it is argued that they are variants of a single premalignant process which might best be termed melanocytic dysplasia. Melanocytic dysplasia is seen in white races, on non exposed and exposed skin. They may be solitary as well as multiple and the majority are non-familial. Although melanocytic dysplasia may be a precursor of a large proportion of malignant melanomas it is suggested that most lesions mature into a benign intradermal melanonaevus. The behaviour of the lesions in any single patient appears to be proportional to the number and cellularity of the lesions and the strength of the family history. A diffuse mottled pattern of melanocytic dysplasia appears to have a particularly unfavourable prognosis. PMID- 4029905 TI - Mycosis fungoides in an epidermoid cyst. PMID- 4029906 TI - Uniform vascular response to different aetiological factors. PMID- 4029907 TI - An overview of child custody laws. AB - The increasing divorce rate, the large number of women in the workforce, and the expanded role of fathers in parenting have led to a dramatic increase in child custody litigation. The law has responded to this growing problem in many ways, the foremost being to shift the emphasis of child custody laws from the rights of the parents to the needs of the child. The author traces the development of child custody laws from English common law, which granted custody to fathers, to the present best-interests-of-the-child standard. Criteria for evaluating the child's best interests, legislation to reduce postdecree litigation and child snatching, and approaches to ease the pain of family breakups, such as joint custody and divorce mediation, are among the many facets of present laws discussed by the author. PMID- 4029908 TI - Patients' release of medical records: involuntary, uninformed consent? AB - The authors reviewed 200 requests for records of psychiatric patients submitted to a university-affiliated hospital in May and June 1983. They looked at the sources of and reasons for the requests and subsequent uses and handling of released information. A survey of 32 patients who released all or part of their records indicated that most felt strongly about limiting access to their records, yet 81 percent felt that release was mandatory to get medical, financial, or other help. Those and other survey findings led the authors to question whether patients' release of information was truly informed and to draw up guidelines that health care providers can use to protect patients' confidentiality. PMID- 4029909 TI - Correlates of acting-out behaviors among young adult chronic patients. AB - The authors studied how the abuse of alcohol and other drugs and the failure to take prescribed medications are related to behavior problems shown by young adult mentally ill persons at home and in the community. The study was based on information provided by case managers for 1,471 clients in the community support program (CSP) sponsored by the National Institute of Mental Health. The study found that alcohol abuse was strongly related to acting out among young CSP clients, but that drug abuse affected their behavior even more adversely. Failure to comply with prescribed medication regimens accounted for a considerable share of the behavior problems exhibited by the young clients, particularly acting out in the community. Age was found to have an attenuating effect on behavior problems. The authors emphasize the need to devise programs to meet the needs of young chronic mentally ill persons. PMID- 4029910 TI - Characteristics of young adults with schizophrenic disorders treated in the community. AB - The authors describe the characteristics of 100 young adults with schizophrenia or schizophrenia-related disorders who are being treated in the community, patients who are at high risk for serious, long-term impairment but have not necessarily developed such impairment yet. In contrast to subjects in some other studies of young adult chronic patients, the patients show great variability in previous levels of functioning, such as employment history, ability to live independently, and drug use. The authors hypothesize that highly individualized assessment and comprehensive treatment provided early in the course of illness can prevent or limit chronic functional disability for many patients; they provide recommendations for such treatment. PMID- 4029911 TI - Paradoxes faced by residents being trained in the psychosocial treatment of people with chronic schizophrenia. AB - The authors describe seven paradoxes that confront psychiatric residents being trained in the psychosocial treatment of chronic schizophrenic patients in community settings. The paradoxes arise because the psychosocial framework necessary for working with such patients challenges the residents' strongly held beliefs and values concerning the nature of psychotherapy and of schizophrenia. The paradoxes result in stress and resistance to learning new approaches and must be clarified and resolved for training to proceed successfully. The authors examine the origins of the paradoxes and the reactions of residents to each, and describe how the supervisory relationships of the training setting can be used to resolve them. PMID- 4029912 TI - Service and patient predictors of continuation in clinic-based treatment. AB - The authors studied 125 chronic patients who entered treatment at five community mental health clinics to identify the patient and service predictors of continuation in treatment. Patients who remained in treatment at the end of one year were significantly more likely than those who dropped out to have received medication at early visits, to have participated in psychotherapy, and to be chronically psychotic. Analysis of the clinics that most successfully retained patients in treatment indicated that service characteristics rather than patient characteristics accounted for the clinics' success. The authors discuss the treatment programs at the two most successful clinics and the implications of the findings for community clinics. PMID- 4029913 TI - Psychiatry and the primary care physician. AB - The author discusses problems that have hindered active collaboration between psychiatrists and primary care physicians, presents models for clinical interaction between them, and describes the role of psychiatrists in the education of primary care physicians. He identifies the differing models of psychiatric and physical medicine as the source of the poor communication that has existed between the two specialties and advocates adherence to a biopsychosocial model as a means of fostering collaboration. He concludes that the psychiatrist can best serve as a teacher and consultant to the primary care physician and as a specialist dealing with serious mental and emotional problems that are beyond the skill of the primary care physician. PMID- 4029914 TI - A school-based program of mental health services. AB - The Brookdale School Program provides mental health consultation and direct services to more than 450 children in a Brooklyn school district through an unusual network involving the local hospital's psychiatry department, the community mental health center, and the school. In the Brookdale program hospital based psychiatrists and school-based social workers, nurses, and psychologists work with teachers, administrators, and parents to provide insight into the emotional and learning difficulties of some children and to set treatment goals. Two case examples are presented. PMID- 4029915 TI - The impact of borderline and schizotypal personality disorders on patients and their families. PMID- 4029916 TI - Meningoencephalitis presenting as depression. PMID- 4029917 TI - Drug misuse in nursing homes: an institutional addiction? PMID- 4029918 TI - Affiliations with multis: rurals becoming picky. PMID- 4029919 TI - Hospital home i.v., RT will see growth spurt. PMID- 4029920 TI - Corporate success includes human values. PMID- 4029921 TI - Medical directors targeted in cost cutting. PMID- 4029922 TI - Programs address the frail elderly's need. PMID- 4029923 TI - PPS prompts focus on multiple job skills. PMID- 4029924 TI - PPAs: fewer start-ups but better operations. PMID- 4029925 TI - What's the market for HMOs and PPAs? PMID- 4029926 TI - Health care policy lessons from Britain. PMID- 4029927 TI - How to select and support the hospital sales team. PMID- 4029928 TI - Physician influence in hospitals: an update. PMID- 4029929 TI - Rural providers in the marketplace. Interview by Clay Mickel. PMID- 4029930 TI - Automation in the hospital pharmacy. PMID- 4029931 TI - Staff reductions: legal and practical issues. PMID- 4029932 TI - Bond growth anticipates Reagan tax reform. PMID- 4029933 TI - Outpatient cancer centers begin to gain attention. PMID- 4029934 TI - Patterns of hospital use by the elderly vary widely by age group: HHS study. PMID- 4029935 TI - Most Blue Cross/Blue Shield plans cover home care: study. PMID- 4029936 TI - IL hospital reduces ER liability risks. PMID- 4029937 TI - Hospital sells its engineering services. PMID- 4029938 TI - Dome adds high-tech touch to MRI shield. PMID- 4029939 TI - What's eroding the hospital's image? PMID- 4029941 TI - Contracts for clinical services rising. PMID- 4029940 TI - Contracts will grow in nonclinical areas. PMID- 4029942 TI - Business needs spur HMO, PPA growth. PMID- 4029943 TI - Mutagenicity tests and the prediction of carcinogenic activity. PMID- 4029944 TI - Unexpected heterogeneity in acute leukemia: mixed lineages and lineage switch. PMID- 4029945 TI - Diagnosis of duodenal and ampullary epithelial neoplasms by endoscopic biopsy: a clinicopathologic and immunohistochemical study. AB - A series of 19 duodenal and 16 ampullary neoplasms was studied to determine their pathologic features on endoscopic biopsy, to evaluate the diagnostic accuracy of this procedure, and to assess the usefulness of immunohistochemical staining for carcinoembryonic antigen (CEA) in these neoplasms. The 11 benign neoplasms (31 per cent) were adenomas, five of which had focal hyperplastic features; the 24 malignant neoplasms (69 per cent) included ten intestinal-type carcinomas (resembling colonic carcinoma), seven anaplastic carcinomas (resembling diffuse gastric carcinoma), two adenocarcinomas in situ, and five lesions of unoriented, cytologically malignant epithelium. Malignancy was suspected endoscopically in 19 of 24 carcinomas, and the majority of the benign neoplasms were described as polyps or plaques. Resections (performed in 20 cases) demonstrated the accuracy of the biopsy diagnoses in 17 cases (85 per cent). In the three discordant cases, diagnosed by biopsy as adenoma in two cases and carcinoma in situ in one, coexistent in situ or infiltrating carcinomas were identified in the resected specimens. Carcinoembryonic antigen (20 cases) was identified mostly along glycocalyceal borders in normal and adenomatous tissues, whereas the carcinomas also showed strong cytoplasmic staining for CEA. Endoscopic biopsy is a valuable procedure in the diagnosis of duodenal and ampullary neoplasms. Correlation of the pathologic features of biopsy specimens with endoscopic appearances may result in more accurate diagnoses. PMID- 4029946 TI - Creatine kinase subunits M and B as markers in the diagnosis of poorly differentiated rhabdomyosarcomas in children. AB - Antibodies against the M and B subunits of creatine kinase were assessed for their usefulness in the diagnosis of poorly differentiated rhabdomyosarcoma. Routinely processed formaldehyde-fixed tissue and the avidin-biotin-peroxidase complex technique were used. The majority of the poorly differentiated and all of the moderately and well-differentiated rhabdomyosarcomas studied showed immunostaining for the M subunit. The rhabdomyoblastic component of malignant "triton" tumors was also positive. Staining, although weak compared with that of the rhabdomyosarcomas, was also observed in a few leiomyosarcomas, hemangioendotheliosarcomas, malignant fibrous histiocytomas, and ganglioneuroblastomas. On the other hand, staining for the B subunit was seen in many types of soft tissue tumors, including rhabdomyosarcoma, Ewing's sarcoma, and (ganglio)neuroblastoma. The results indicate that creatine kinase subunit M is a useful marker for distinguishing poorly differentiated rhabdomyosarcoma from other types of small round cell tumors in children, such as neuroblastoma, Ewing's sarcoma, and malignant lymphoma. PMID- 4029947 TI - Ultrastructural and immunohistochemical characteristics of mucoepidermoid carcinoma of the breast. AB - Mucoepidermoid carcinoma is a rare subtype of breast carcinoma. In an attempt to elucidate the histogenesis of these tumors, two mucoepidermoid carcinomas were studied electron microscopically and immunohistochemically with antisera to S-100 protein and epidermal cytokeratin. Light microscopic examination showed these tumors to be composed of mixtures of neoplastic mucus-secreting, squamous, and intermediate cells. Ultrastructural examination revealed squamous cells, mucus secreting luminal cells, and classic myoepithelial cells. The intermediate cells, which contained focal peripheral myofilaments with dense bodies and pinocytotic vesicles associated with centrally aggregated tonofilaments, were interpreted as modified myoepithelial cells. Classic dendritic myoepithelial and intermediate (modified myoepithelial) cells stained with antisera to S-100 protein and epidermal cytokeratin. Both the ultrastructural and the immunohistochemical features indicate that myoepithelial and duct luminal cells play an important role in the histogenesis of mucoepidermoid tumors of the breast. PMID- 4029948 TI - Idiopathic pulmonary arterial trunk aneurysm presenting as cor pulmonale: report of a case. AB - An elderly woman who presented with cor pulmonale and intractable right heart failure was found at autopsy to have a thrombosed aneurysm of the pulmonary arterial trunk. This case is unusual in that no associated congenital cardiopulmonary anomaly, vascular myxoid degeneration, pulmonary parenchymal disease, or thromboembolism was found. PMID- 4029949 TI - Intrauterine closure of the ductus arteriosus in association with prune belly syndrome. AB - Findings from the autopsy of a preterm neonate with in utero anatomic closure of the ductus arteriosus in association with prune belly syndrome are presented. Marked bladder distention, a major feature of prune belly syndrome, has secondary mechanical effects on fetal thoracic organs, and the fetus might have been exposed to chronic intrauterine stress. This could have affected the prenatal closure of the ductus arteriosus, although no definitive conclusion can be made. PMID- 4029950 TI - Endocardial fibroelastosis and myocardial calcification secondary to an anomalous right coronary artery arising from the pulmonary trunk. AB - The case of an infant with endocardial fibroelastosis and a coexistent anomalous right coronary artery that originated from the pulmonary trunk is presented. The causal relation between the two conditions is discussed. PMID- 4029951 TI - Cystic disease of the kidney in newborns. PMID- 4029952 TI - Inversion (14)(q12qter) or (q11.2q32.3): the most frequently acquired rearrangement in lymphocytes. AB - In a large study of chromosome rearrangements occurring in human lymphocytes from normal subjects, inv (14)(q12qter) or (q11.2q32.3) is found to be the most frequent, affecting 0.15% of mitoses. The same inversion is observed in the lymphocytes of the chimpanzee, indicating the ancestry of this inversion. It is not induced by ionizing radiations, and its frequency may be increased in Fanconi anemia, but not in ataxia telangiectasia. It may represent one of the steps of the process of leukemogenesis. PMID- 4029953 TI - Phenotype and gene frequencies of acid phosphatase (s-AcP) in the human parotid saliva. AB - Genetic polymorphism of the human parotid salivary acid phosphatase (s-AcP) in the Japanese population is described. The use of polyacrylamide gel isoelectric focusing electrophoresis with the pH range of 4.0-6.5 enabled us to discern three variant patterns controlled by two codominant alleles at the single autosomal locus. The two alleles were designated s-AcP:A and s-AcP:a, and the gene frequencies calculated from 183 Japanese subjects were s-AcP:A = 0.2268 +/- 0.022, s-AcP:a = 0.7732 +/- 0.022, respectively. The distribution of phenotypes fitted the Hardy-Weinberg equilibrium. PMID- 4029954 TI - Replication of X chromosomes in complete moles. AB - DNA replication patterns of X chromosomes in complete hydatidiform moles were studied using cultured fibroblasts from three 46,XX moles resulting from duplication of a haploid sperm, and from a 46,XY mole originating from dispermy. Control cultures included skin fibroblasts from an adult woman and a female fetus as well as PB lymphocytes from an adult woman. Cultures were treated with 5-bromo deoxyuridine for the last 2-4 h of the S phase, and the chromosome slides prepared were stained by the Hoechst 33258-Giemsa procedure. Each of the three XX moles studied revealed one early-replicating and one late-replicating X chromosomes, while the XY mole revealed one early-replicating X chromosomes. DNA replication patterns of molar X chromosomes were similar to those of adult and fetal fibroblasts, but different from those in adult lymphocytes. These findings indicate that DNA replication kinetics of molar fibroblasts are tissue-specific rather than origin- or developmental-stage specific. PMID- 4029955 TI - G-6-PD Jalisco and G-6-PD Morelia: two new Mexican variants. AB - Two new G-6-PD variants designated G-6-PD Jalisco and G-6-PD Morelia were identified in two unrelated Mexican families. An additional G-6-PD variant was found in each family: G-6-PD Trinacria and G-6-PD A-. In both families compound heterozygotes were identified. G-6-PD Jalisco and G-6-PD Morelia belong to Classes 3 and 4, respectively. G-6-PD Morelia is the first variant from its class with a high Km for NADP and a low Ki for NADPH. PMID- 4029956 TI - Scalp defect associated with postaxial polydactyly: confirmation of a distinct entity with autosomal dominant inheritance. AB - The association of postaxial polydactyly type A and congenital scalp defect in a 15-year-old severely mentally retarded male confirms the previously reported suggestion that the combination of both anomalies represents a new distinct entity with autosomal dominant inheritance and variable expression. PMID- 4029958 TI - Increased birth weight in psoriasis--another expression of a "thrifty genotype"? PMID- 4029957 TI - Maple syrup urine disease: two different forms within a single family. AB - A family is reported in which the index case presented with an acute form of maple syrup urine disease (MSUD), whereas two of her sisters and her father were found to have an almost asymptomatic form of the disease. It is proposed that the members of this family are compound heterozygotes for the classical deficient mutant gene and for a "variant" allele. PMID- 4029959 TI - Genetic relationships between Indians and their neighboring populations. AB - Using gene frequency data for 18 protein and blood group loci, we studied the genetic relationships of four Indian subcontinent populations (peoples from Punjab, Gujarati, Andhra Pradesh, and Bangladesh) with their neighboring populations (Iranians, Afghans, Sinhalese in Sri Lanka, Nepalese, Bhutanese, Malays, Bataks in northern Sumatra, and Chinese). The results obtained indicate that the four Indian subcontinent populations and the Sinhalese are genetically closer to Iranians and Afghans (Caucasoid) than to the other neighboring Mongoloid populations. Genetic distance analysis shows a clear-cut dichotomy between the Caucasoid and Mongoloid populations. PMID- 4029960 TI - Haptoglobin groups and rheumatoid arthritis. AB - Haptoglobin types were determined in 200 patients with rheumatoid arthritis (RA) subdivided according to sex and familial occurrence of polyarthritis. A highly significant excess of the Hp2 gene was found among patients with a family history of polyarthritis, more pronounced among males. The possible association between Hp2 and predisposition for increased immune reactivity is discussed. PMID- 4029961 TI - Variability of selection opportunities with changing socio-cultural environments. AB - Opportunity for selection has been studied against their contrasting socioeconomic and cultural backgrounds in two endogamous populations, namely, Brahmins and Jalaris of Visakhapatnam, India. Total selection was slightly higher among the better off Brahmins than in Jalaris. But a marked qualitative and quantitative variation was found in the contributing components; the fertility differential was circa 60% in Brahmins while the mortality differential was circa 60% in Jalaris according to the Crow Index. The decreased mortality differential in Brahmins suggests that this component was directly affected by the better socio-economic level and reflects on the population's transitional phase. Further, the If value fell to a half in women who completed their fertility by family planning when compared to women who completed their fertility by menopause, thus reducing the variance in fertility component in the family planning group. PMID- 4029962 TI - Nonorgan-specific autoantibodies and immunoglobulin allotypes in relatives of patients with monoclonal gammopathy. AB - Polyclonal immunoglobulin increase, rheumatoid factor, antinuclear antibodies and cold lymphocytotoxins were detected 10, 8, 7 and 8 times, respectively, in a group of these informative families (22, 17 and 29 subjects tested, respectively). Each family included at least 1 subject with a monoclonal gammopathy in addition to that of the proband. No correlation could be shown between any of these abnormalities and Gm haplotypes. Nonetheless, it is worth noting that 6 out of 41 relatives under 30 years of age had cold lymphocytotoxins. PMID- 4029963 TI - Segregation analysis of ocular refraction and myopia. AB - Segregation analysis of ocular spherical refraction data using a unified model resulted in rejection of a Mendelian hypothesis of genetic transmission in nuclear families of both Japanese and European ancestries. Similar analyses of families which included at least 1 myope gave no evidence for the hypothesis that myopia is determined in part by a major gene. Most of the variation associated with ocular refraction, or with myopia, seems to be nongenetic in origin. PMID- 4029964 TI - A genetic and demographic study of hemophilia A in Brazil. AB - A genetic and demographic study was made of patients with hemophilia A in Rio Grande do Sul, Brazil, during a 15-year period. The study comprised 104 patients belonging to 70 pedigrees. Life expectancy at birth increased from 32.2 to 44.5 years, mean age of death from 11.1 to 14.6 years, and survival to maturity from 33 to 38%. However, fertility decreased from an average number of 1.6 to 0.8 children. Among the normal brothers, the average number of offspring was decreased from 2.2 to 1.5 children. The fitness of patients in this population, in spite of the increase of the average life expectancy, was decreased due to the decrease of fertility, from 0.47 to 0.43 using the normal brother as control, and from 0.35 to 0.20 using the general population as control. PMID- 4029965 TI - C3 and C6 complement types in schizophrenia. AB - C3 and C6 complement types were studied in schizophrenic patients and controls. The distributions of the three common C3 types (F, FS and S) among the patients was significantly different from that in the controls (p less than 0.005) and the frequency of the C3F gene was significantly increased (p less than 0.0005) among the patients. There were no significant differences in C6 gene or phenotype frequencies between patient and controls. PMID- 4029966 TI - Placental alkaline phosphatase polymorphism in northern Greece. AB - The placental alkaline phosphatase (Aph) polymorphism was studied in Northern Greece. A new rare placental Aph variant was described. PMID- 4029967 TI - Association between C3 complement types and bronchial asthma. AB - A statistically significant association was found between the C3F gene and bronchial asthma. The relative risk for bronchial asthma among individuals carrying the C3F gene was 4.0. PMID- 4029968 TI - A possible clinical implication of homozygous inversions of 9qh regions with Cornelia de Lange syndrome (CLS). AB - Several investigators have attempted to correlate chromosomal abnormalities with Cornelia de Lange Syndrome (CLS), but none of them have been conclusive. The homozygous inversion of 9qh found in the present case has not been found previously. It remains to be clarified whether the presence of this finding in CLS was simply a coincidence or whether homozygosity for such inversions may result in CLS. PMID- 4029969 TI - Association between C3 complement types and Indian childhood cirrhosis. AB - A highly significant association was found between the C3F gene and indian childhood cirrhosis (ICC), a major cause of death among young children in India. The relative risk for ICC among individuals carrying this gene was 12.5. PMID- 4029970 TI - Statistical testing in dermatoglyphic studies. PMID- 4029971 TI - A system for measuring tremor intensity in rats. PMID- 4029972 TI - Sensitivity analysis of depth EEG electrodes to dipolar electric sources. PMID- 4029973 TI - Sensitivity of the human eye to power frequency electric fields. PMID- 4029974 TI - Forward and inverse potential field solutions for cardiac strands of cylindrical geometry. PMID- 4029975 TI - Fluctuations of human tapping intervals. PMID- 4029976 TI - Investigation of methods to estimate ultrasonic attenuation of soft tissue. PMID- 4029977 TI - Modeling of the transfer function of the heart-thorax acoustic system in dogs. PMID- 4029978 TI - A tactile vision-substitution system for the blind: computer-controlled partial image sequencing. PMID- 4029979 TI - Exposure of human models in the near and far field--a comparison. PMID- 4029980 TI - Ku and K-band irradiation of giant algal cells: the absence of detected bioeffects at 100 W/m2. PMID- 4029982 TI - Fluctuations in tracer amounts in a compartmental system with a Markovian transition process. PMID- 4029981 TI - The use of two-dimensional echocardiograms in the detection of myocardial infarction in canines. PMID- 4029983 TI - A research prototype of an inkbraille reading aid. PMID- 4029984 TI - An unbalanced electric applicator for RF hyperthermia. PMID- 4029985 TI - Echo visualisation of pacemaker lead. PMID- 4029986 TI - Predictive value of disopyramide provocation in chronic bifascicular block--long term follow-up with a bradycardia indicating pacemaker. PMID- 4029987 TI - Ventricular septal rupture following acute myocardial infarction: contrast two dimensional echocardiographic diagnosis. PMID- 4029988 TI - Poisoning with a large dose of digitalis. PMID- 4029989 TI - Stable right ventricular endocardial permanent pacing via left superior vena cava. PMID- 4029990 TI - Utility of two-dimensional echocardiography in the detection of left ventricular intracavitary mass. PMID- 4029991 TI - Cross-talk in a DDD pacemaker leading to faulty programming. PMID- 4029992 TI - Thrombosis of mitral valve prosthesis during pregnancy--successful surgical treatment. PMID- 4029993 TI - Right atrial myxoma--a report of two cases. PMID- 4029994 TI - Close encounters with the "outer space". PMID- 4029995 TI - Primary pulmonary hypertension: a therapeutic dilemma. PMID- 4029996 TI - Acute effect of sublingual nifedipine on right ventricular systolic time intervals in primary pulmonary hypertension--an echocardiographic study. PMID- 4029998 TI - On the double presystolic wave of the jugular tracing. PMID- 4029997 TI - Dual-chamber pacing for symptomatic bradyarrhythmias. PMID- 4029999 TI - The modified Vosschulte repair for congenital coarctation of the aorta--an experience of 65 cases. PMID- 4030000 TI - The effect of oral contraceptive drug on cardiovascular system, liver & kidneys. PMID- 4030001 TI - Characterization of prosthetic groups of naphthalene oxygenase from Corynebacterium renale. PMID- 4030002 TI - Depolymerization of capsular polysaccharide by glycanase activity of Klebsiella bacteriophage phi 51. PMID- 4030003 TI - Effect of zinc deficiency on kinetics of ribulose-1,5-biphosphate carboxylase of Oryza sativa L. and Pennisetum americanum (L.) Leeke. PMID- 4030004 TI - Iodide carrier in isolated cells of stomach. PMID- 4030005 TI - Biological synthesis of L-ascorbic acid in goat prostate. PMID- 4030006 TI - Conformational studies on adenosine and its analogs by proton magnetic resonance. PMID- 4030007 TI - MINDO/3 calculations of carcinogen activities of polycyclic hydrocarbons. PMID- 4030008 TI - Studies on active site of goat pancreatic carboxypeptidase A: modification of histidine residues. PMID- 4030009 TI - [Meaning and aims of a pollen information service]. AB - Two years ago, the foundation "Deutscher Polleninformationsdienst" was established in Cologne/West Germany. Measurements from pollen collectors, together with the weather forecast were combined to a prognosis of pollen flight for the following 2 days. In spring and summer, these informations were given to the public services twice a week. Now, in nearly all regions of West Germany, pollen measurement points are established. The aim of a pollen information service is to give further information to pollinosis patients and physicians on their medicaments, i.e. how to use them effectively and prophylactically. PMID- 4030010 TI - [Circulating immune complexes, specific IgE against food and inhalation allergens, serum histamine levels and disorders of intestinal permeability in atopic patients before and after test meals]. AB - Specific IgE antibodies against 25 food and 3 respiratory allergens were investigated in 35 AD patients and 26 healthy controls before and after challenge meals (CM). The frequency of positive results showed a significant increase after CM (+ 58%) with no influence on reaction specificity. Increased serum CIC levels with IgG, IgE and IgM were recorded in 34, 47 and 54% of the 35 AD patients respectively, whereby only the IgE-CIC demonstrated an increase of frequency and mean levels after CM. In 4 out of 5 atopic patients, significant higher histamine values were registered half an hour after CM, furthermore 23 out of 61 fasted patients demonstrated increased serum histamine levels. However, no direct correlation could be noticed between the increased intestinal permeability of the investigated patients on the one hand and the serum histamine levels or the presence of IgE-CIC on the other hand. The relations between single parameters as well as their clinical significance in AD patients after CM administrations are discussed. PMID- 4030011 TI - [Antibody diversity and network theory--a hypothesis]. AB - The diversity of antibody specificities arises during the development of the immune system by recombination of genes and by spontaneous mutations and is not yet determined in the germ-cell, as earlier supposed. The network theory describes how antibody and lymphocyte populations are regulated recognizing each other by idiotopes. It is proposed that protection against autoaggression by an immune system with a genetically mostly uncontrolled high variability of specificities is based on anti-idiotypic antibodies which express autoantigen structures. There are suggestions that essential functions of the immune system consist not only in protection against microbes and immunological surveillance but also in regulatory effects on nonimmunological body-cell systems. PMID- 4030012 TI - [Nail changes and alopecia areata]. PMID- 4030013 TI - [Plantar prickle cell epithelioma (epithelioma cuniculatum). Description of 3 cases]. PMID- 4030014 TI - [Eruptive capillary hemangioma in an adult, with partial autoresolution]. PMID- 4030015 TI - [Pigmentation caused by Cordarone]. PMID- 4030016 TI - [Malignant acanthosis nigricans with an unusual clinical expression]. PMID- 4030017 TI - [Demonstration of S-100 protein in a cutaneous cell population]. PMID- 4030018 TI - [Effect of oral administration of haptens in sensitized subjects with contact allergic eczema. II). Personal contribution]. PMID- 4030019 TI - [Consideration on a case of lues tarda]. PMID- 4030020 TI - [Minoxidil for local application in the treatment of alopecia]. PMID- 4030021 TI - [Alopecia areata and treatment with the diethylester of squaric acid. Behavior of lymphocyte subpopulations]. PMID- 4030022 TI - [Treatment of alopecia areata with topical dinitrochlorobenzene. Results and follow-up]. PMID- 4030023 TI - [Grover's disease and neoplasms: a non-casual association?]. PMID- 4030024 TI - Hemolysis and suppression of neutrophil chemotaxis by a low molecular weight component of human burn patient sera. AB - During the past year, we have reported the isolation and characterization of a low molecular mass (less than 5000 Da) complex (SAP), having profound immunosuppressive activity, found in the plasma of patients with major thermal injuries. Our continued studies have revealed that non-cytotoxic inhibition of neutrophil chemotaxis by SAP is paralleled by erythrocyte hemolysis by the same compound. Both neutrophil inhibitory and hemolytic activities appear to be a function of the peptide portion of SAP (determined by sensitivity to trypsin and pronase), which is augmented by the presence of sialic acid in the complex (activity eliminated by the addition of neuraminidase). The lipid portion of SAP, which is critical to its neutrophil immunosuppressive activity, does not appear to participate in erythrocyte hemolysis. Hemolytic activity of SAP is not due to protease activity, and does not appear to be receptor dependent. However, it is completely dependent upon the presence of calcium. The hemolytic activity of SAP appears to be abrogated by the addition of cerium nitrate, leading to a hypothesized relationship of SAP to the immunological activity of "burn toxin", previously described in detail (Schoenenberger, G.A. (1975) Monogr. Allergy 9, 72 139). PMID- 4030025 TI - Subset specificity of lupus antilymphocyte antibodies studied by two-colour microfluorimetry. AB - Subset specific lymphocytotoxic activity of lupus sera was studied by a combination of selective immunofluorescence labelling and complement-mediated lysis. Most frequently death of B cells was detected. Many of the sera caused lysis of T lymphocytes; selective cytotoxicity against suppressor T cells could be observed less frequently. All the anti-T4, anti-T8 and anti-B lymphocyte antibodies proved to be cold reactive. PMID- 4030026 TI - Basal immunoglobulin serum concentration and isotype distribution in relation to the polygenic control of antibody responsiveness in mice. AB - Serum Ig concentration and isotype distribution were determined in the high (H) and low (L) responder lines selected for antibody response to complex immunogens. Data were recorded in normal and postimmunization sera from the H and L lines produced by five independent selective breedings (selections I, II, III, IV, and V). Ig levels were much higher in H than in L mice of all the selections. In four selections this interline difference increased further after immunization with the selection antigens. This is in agreement with the general effect of the polygenic control of antibody responses operating in H and L lines. The Ig isotype profiles of normal sera were different in each line; however, similitudes were noticed between H and L lines in selections I and II. In contrast, in selections III, IV, and V a similar interline difference was observed: the lack of IgG2a isotype in L lines only. After immunization there were minor alterations of the isotype profiles except in the H lines of selections III and IV, in which a clear inverse modification of IgG1 and IgG2a proportions occurred. The characteristic pattern of each selection may be partially dependent on isotype restricted regulatory effects in relation to the immunization procedure used for selective breeding. PMID- 4030027 TI - Corticosteroid-induced cleft palate: cis interaction of MHC genes and hybrid resistance. PMID- 4030028 TI - Enhancement of Japanese encephalitis virus growth in vitro by concanavalin A. PMID- 4030029 TI - Radioactive bromide partition test in the diagnosis of tubercular meningitis in children. PMID- 4030030 TI - Effect of immunization with formalin killed cells in complete Freund's adjuvant in experimental candidosis. PMID- 4030031 TI - Cellular radioimmunoassay for antibodies to spermatozoa. PMID- 4030032 TI - Quality & quantity of dietary protein & acute endosulphan metabolic toxicity in rat liver microsomes. PMID- 4030033 TI - Antibody-dependent cell mediated cytotoxicity against nucleated target cells in patients with squamous cell carcinoma of uterine cervix. PMID- 4030034 TI - Diet, body fat & plasma lipids in breast cancer. PMID- 4030035 TI - Role of intraoperative wound contamination in post-operative wound infection in laparotomy. PMID- 4030036 TI - Central thermoregulatory effect of 1, 1 dimethyl-4-phenyl piperazine iodide. PMID- 4030037 TI - Effect of intratracheally instilled benzo (a) pyrene on the pulmonary & hepatic protective enzymes in normal & vitamin A deficient rats. PMID- 4030038 TI - The mini health centre scheme in Tamil Nadu: a study of inputs. PMID- 4030039 TI - Evidence of early degenerative changes in large arteries in human essential hypertension. AB - Noninvasive evaluation of brachial artery diameter (pulsed Doppler velocimetry) and pulse wave velocity (strain gauge mechanography) was performed in 23 normal subjects and 49 patients with uncomplicated essential hypertension. Pulsatile arterial function was described in terms of derived characteristic impedance and arterial compliance. Compared with normal controls, hypertensive patients had greater arterial diameter (p less than 0.01) and pulse wave velocity (p less than 0.001). Two nomograms obtained from normal subjects relating the product of age and diastolic pressure to diameter and pulse wave velocity were used for analysis of the hypertensive group; 35 patients were inside the 95% confidence limits of the diameter and pulse wave velocity nomograms (Group 1), while 14 patients were outside the pulse wave velocity nomogram (Group 2). Age and mean pressure were similar, but pulse wave velocity was higher (p less than 0.001), arterial compliance lower (p less than 0.001), and characteristic impedance higher (p less than 0.001) in Group 2 than in Group 1. The amplitude of pulse pressure was higher in Group 2 than in Group 1 (p less than 0.001), and a negative correlation was found between pulse pressure and arterial compliance in Group 2, but not in Group 1. Thus, in the majority of hypertensive patients, arterial modifications could be related to the normal influence of age and pressure. In contrast, other patients exhibited features suggesting excessive arterial stiffness, manifested by abnormally high pulse wave velocity, decreased arterial compliance, and increased characteristic impedance. PMID- 4030041 TI - Blood pressure changes during adolescence and subsequent adult blood pressure level. AB - Serial data were analyzed for blood pressure recorded between the ages of 9 to 18 years for 278 children and for a subset of this group whose blood pressure was measured at the age of 30 +/- 5.0 years (n = 93). Blood pressures were measured by auscultation over the antecubital fossa with the participant seated. Systolic blood pressure was recorded when the first sound was heard, and diastolic blood pressure was recorded when all sounds disappeared (fifth phase). A linear regression model was fitted to the data for each individual, and adjustments were made for regression toward the mean using maximum likelihood procedures. There were no significant correlations between the estimated initial values of blood pressure and the rate of change from 9 to 18 years of age. The associations between the levels of blood pressure at 9 years of age and at 30 years of age were significant for systolic blood pressure only in male subjects and were not significant for diastolic blood pressure in either sex. The correlations between the rate of blood pressure change from 9 to 18 years of age and blood pressure levels at 30 years of age were nonsignificant. When the initial values and the rate of change in blood pressure from 9 to 18 years of age were taken into account simultaneously, they accounted for approximately 20% of the variation in systolic blood pressure levels at 30 years of age. This finding indicates that children with higher blood pressure levels at about 9 years of age and with rapid increases in blood pressure during pubescence may have an increased risk of becoming hypertensive.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4030040 TI - Endogenous angiotensin-aldosterone-pressure relationships during sodium restriction. AB - The effects of moderate restriction of dietary sodium and potassium supplementation on plasma levels of renin, angiotensin II, aldosterone, and cortisol and on arterial pressure were studied in 12 patients with mild essential hypertension. To define hormone-blood pressure relationships, venous hormone levels were measured hourly and intra-arterial pressure continuously for 24 hours after 4 to 6 weeks of sodium restriction, 4 to 6 weeks of potassium supplementation, and a similar period of control diet. Our results show that compared with the control diet, moderate sodium restriction was associated with increased levels of aldosterone but no overall change in renin, angiotensin II, or cortisol levels. Further, slopes of regression lines relating log renin and log angiotensin II to aldosterone were increased, as were log cortisol/aldosterone regression lines. On the contrary, regression lines of log renin and log angiotensin II versus arterial pressure were unaltered by sodium restriction. Hormone and blood pressure relationships were not changed by the potassium supplemented diet. Although confirmatory data are needed, our findings suggest that moderate sodium restriction enhances aldosterone responsiveness to endogenous angiotensin II and adrenocorticotropic hormone without diminishing the pressor activity of endogenous angiotensin II. These results may explain in part the disappointingly small hypotensive effect of modest sodium restriction in mild essential hypertension. PMID- 4030042 TI - Inability of dorsal spinal rhizotomy to prevent renal wrap hypertension in rats. AB - Renal hypertension has been shown to be prevented and reversed by renal denervation. It has been postulated that the afferent nerves from the kidney are responsible for mediating the hypertensive stimulus that activates the sympathetic nervous system and increases arterial pressure. This study was designed to directly test the hypothesis that the afferent renal nerves are necessary for the development and maintenance of renal hypertension. In the first experiment, dorsal spinal rhizotomies or sham rhizotomies were performed in rats between T9 and L1, through which afferent renal nerves have been shown to traverse. After the one-kidney, one-wrap procedure, the increase in systolic arterial pressure and water intake was similar in the two groups of rats. To determine whether the removal of afferent renal nerves reversed the hypertensive process, animals with established renal hypertension were subjected to dorsal rhizotomy or the sham-rhizotomy procedure. Again, there was no significant effect on systolic arterial pressure and water intake. Although combined dorsal and ventral rhizotomy and subdiaphragmatic vagotomy did not affect the onset of hypertension, spinal transection at the level of C8 effectively prevented the rise in arterial pressure. Although efferent neural mechanisms contribute to the hypertensive process, these studies suggest that afferent renal nerves are not directly involved in the development and maintenance of one-kidney, one-wrap renal hypertension. PMID- 4030044 TI - Role of acetyl glyceryl ether phosphorylcholine in blood pressure regulation in rats. AB - The role of an endogenously occurring acetyl glyceryl ether phosphorylcholine (AGEPC) in blood pressure regulation was studied with an AGEPC antagonist in rats with hypertension of various etiologies. The hypotensive activity of an intravenously injected AGEPC was competitively suppressed by the intravenous infusion of 3-(N-n-octadecylcarbamoyloxy)-2-methoxypropyl-2-thiazolioethylphospha te (CV-3988) and was dose-dependent. The CV-3988 was infused intravenously into one- and two-kidney, one clip hypertensive, deoxycorticosterone-salt hypertensive, adrenal regeneration hypertensive, spontaneously hypertensive, and normotensive control rats. The increase in blood pressure caused by CV-3988 infusion in spontaneously hypertensive and normotensive control rats was significant (p less than 0.01 and p less than 0.001, respectively, at 60 min) compared with that caused by vehicle infusion. The increase was not seen in rats with secondary hypertension. In rats with two-kidney, one clip hypertension, the initial rapid decrease in blood pressure seen after unclipping was significantly (p less than 0.05) inhibited by CV-3988 infusion as compared with that by vehicle infusion. These results suggest that endogenous AGEPC may participate in the blood pressure regulation and pathophysiology of some forms of hypertension in rats. PMID- 4030043 TI - Cardiac mass and peripheral vascular structure in hydralazine-treated spontaneously hypertensive rats. AB - We have examined the effect of antihypertensive treatment on heart weight and on structural and functional characteristics of isolated mesenteric resistance vessels (internal diameter 170-220 micron) in spontaneously hypertensive rats (SHR) and in Wistar-Kyoto rats (WKY). The SHR and WKY were treated with hydralazine from the age of 4 weeks and were examined at ages 12 to 14 weeks and 23 to 27 weeks. Treated SHR had a mean blood pressure as much as 29% below that of control WKY, which in turn was 25 to 40% less than that of control SHR. In 12- to 14-week-old rats the heart to body weight ratio (which in control SHR was 13% greater than of WKY) was unaffected by treatment. Thereafter, the heart to body weight ratio of treated SHR did not increase as much as usual. At both ages, the media thickness and contractile response of the resistance vessels of the SHR (which were, respectively, 37% and 30% greater than those of vessels of WKY) were unaffected by treatment. However, because treatment caused a small (8%) increase in the lumen diameter of the vessels of the SHR, treatment did cause small, but possibly physiologically important, decreases both in the media to lumen ratio (11%) and in the pressure against which these vessels would have been able to contract (10%). Treatment had little effect on the pharmacological characteristics of vessels of either SHR or WKY. The results suggest that the increased heart weight, media thickness, and contractile response in mesenteric resistance vessels of SHR up to ages 23 to 27 weeks are due primarily to factors other than increased pressure. PMID- 4030045 TI - Exercise training attenuates stress-induced hypertension in the rat. AB - The ability of exercise training to block the generation of hypertension produced by chronic stress in the borderline hypertensive rat was tested. Twenty-three male borderline hypertensive rats, F1 offspring of spontaneously hypertensive and Wistar-Kyoto rats, were divided into three groups. Two groups (8 rats per group) were subjected to 2 hours of daily, predictable, uncontrollable tail shock for 12 weeks. One of these groups was also given 2 hours of daily swim stress (exercise trained). A third group served as a maturation control and received neither intervention (n = 7). After 12 weeks of stress, direct recording of blood pressure verified the pattern observed with tail cuff: shock only group, 180/118 +/- 3/3 mm Hg; exercise-trained and shocked group, 166/108 +/- 4/2 mm Hg; and control group, 160/98 +/- 6/4 mm Hg (mean +/- SEM). Systolic and diastolic blood pressures in the shock only group were significantly higher than in both the other groups (p less than 0.05). The control group differed from the exercise trained and shocked group only in diastolic BP (p less than 0.05). During a short term stress session plasma norepinephrine levels in the exercise-trained and shocked group were significantly lower than those in the shock only group (555 +/ 56 vs 776 +/- 84 pg/ml; p less than 0.05). These results indicate that an alteration of autonomic function resulted from the exercise training, but its contribution to the resistance of the exercise-trained and shocked rats to stress induced hypertension is unclear. PMID- 4030046 TI - Angiotensinogen levels in the brain and cerebrospinal fluid of the genetically hypertensive rat. AB - The present experiments were designed to document changes in the regional distribution of angiotensinogen in the rat brain with the development of hypertension in spontaneously hypertensive rats (SHR) relative to age-matched normotensive Wistar-Kyoto rats (WKY). Levels of angiotensinogen were measured in discrete brain nuclei and cerebrospinal fluid from rats at 4, 7, and 16 weeks of age and in cerebrospinal fluid obtained by cisternal puncture at 7 and 16 weeks. Age-dependent changes in angiotensinogen were found, with levels higher in both strains at 4 weeks of age compared with 7 or 16 weeks. In contrast, plasma levels of angiotensinogen were essentially the inverse of the brain levels, low at 4 weeks and higher at 7 and 16 weeks. Levels in a number of regions adjacent to the rostral third ventricle from the 4-week-old SHR (prehypertensive phase) were significantly elevated relative to the WKY (p less than 0.05), while levels in the amygdala and posterior hypothalamus were significantly lower in the SHR (p less than 0.05). In 7-week-old rats (evolving phase), levels in nine brain regions were significantly elevated in the SHR relative to the WKY and included the nucleus tractus solitarii (p less than 0.01). Unlike the prehypertensive and evolving phases, in 16-week-old rats (maintenance phase) only two brain areas, the nucleus of the diagonal band and the lateral hypothalamus, had significantly elevated levels in the SHR (p less than 0.05). Cerebrospinal fluid levels of angiotensinogen did not correlate well with brain levels of angiotensinogen.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4030047 TI - Mesenteric vascular reactivity in dexamethasone-treated hypertensive rats. AB - Possible alterations in mesenteric vascular reactivity to norepinephrine, angiotensin II, and arginine vasopressin and its relationship to prostaglandins in dexamethasone-induced hypertension in rats were investigated. The animals were treated with dexamethasone or its vehicle (sesame oil) for 1 day (1.8 mg/kg) and for 14 days (1.8 mg/kg/wk). The superior mesenteric artery with its branches was isolated and perfused with Tyrode's solution at a constant flow rate of 5 ml/min. Administration of norepinephrine (1-10 nmol), arginine vasopressin (0.03-0.3 nmol), or angiotensin II (0.1-1 nmol) produced vasoconstriction and increased the output of 6-keto-prostaglandin F1 alpha and prostaglandin E2 in a dose-related manner in mesenteric vessels. Administration of 10 nmol bradykinin or 19 nmol A23187 enhanced the output of prostaglandins without altering vascular tone. The vasoconstrictor response to arginine vasopressin, but not norepinephrine or angiotensin II, was enhanced in mesenteric vessels from rats treated with dexamethasone for 14 days but not for 1 day. In contrast, the output of basal as well as norepinephrine, arginine vasopressin, angiotensin II, bradykinin, or A23187-induced prostaglandin output was significantly reduced in mesenteric vessels from rats treated with dexamethasone for 1 or 14 days. Prostaglandin output in mesenteric arteries from rats treated with dexamethasone for 1 and 14 days was not different. These data indicate that dexamethasone treatment for longer but not for shorter periods results in a selective increase in vascular reactivity of mesenteric vessels to arginine vasopressin that is independent of prostaglandin synthesis. The increase in vascular reactivity to arginine vasopressin during long-term dexamethasone treatment may contribute to the development or maintenance, or both, of glucocorticoid-induced hypertension. PMID- 4030048 TI - Endogenous opiate peptides, stress reactivity, and risk for hypertension. AB - Endogenous opiate peptides can regulate neuroendocrine and circulatory responses to behavioral stress and may be important in the pathogenic effects of sympathoadrenal reactivity. We tested this hypothesis by examining the effect of the opiate antagonist naloxone on blood pressure responses to behavioral stress in young adults with high, medium, or low casual blood pressures. Naloxone increased mean arterial pressure responses to stress in subjects with low casual pressure, but had no significant effect on responses in subjects with high casual pressure. These results suggest opioidergic inhibition of sympathetic nervous system responses may be deficient in persons at risk for essential hypertension. PMID- 4030050 TI - Hypertension in a 74-year-old man with hydronephrosis and coronary disease. PMID- 4030049 TI - NIH report on research challenges in nutrition and hypertension. PMID- 4030051 TI - Sodium chloride, extracellular fluid volume, and hypertension. PMID- 4030052 TI - C-reactive protein in clinical practice. PMID- 4030053 TI - Meningococcal disease in Delhi. PMID- 4030054 TI - Cerebrospinal fluid sialic acid in tuberculous meningitis. PMID- 4030055 TI - Copper studies in liver disorders. PMID- 4030056 TI - Perinatal mortality. PMID- 4030057 TI - Social factors influencing infant mortality. PMID- 4030058 TI - C-reactive protein in neonatal infections. PMID- 4030059 TI - Breast milk composition in relation to gestation. PMID- 4030060 TI - Double versus single surface phototherapy in neonatal hyperbilirubinemia. PMID- 4030061 TI - Cystic angiomatosis of bone. PMID- 4030062 TI - Increased incidence of pyogenic meningitis in Agra. PMID- 4030063 TI - [Vitamin A in the serum of healthy probands and clinical groups]. AB - The estimation of vitamin A in serum of patients suffering from different diseases (M. Crohn, Hypothyroidism, Hyperthyroidism, Liver cirrhosis, Renal insufficiency, Carcinoma of Prostate, ENT-Carcinomas) and healthy controls by means of a recent developed method (HPLC) is reported. Decreased and increased vitamin A serum levels had been reported in literature during different diseases but we could not reveal identical results in all cases. Significantly lowered values were only estimated in patients suffering from liver cirrhosis whereas increased vitamin A serum levels were determined during renal insufficiency. In hypo- or hyperthyroidism there was no difference from healthy persons. In patients with Crohn's disease the distribution of vitamin A concentrations in serum was bimodal, probably depending on extension and localization of the process. Patients with carcinoma of the prostate had only minor deviations from the normal value, whereas patients with tumors of the larynx had in part very low vitamin A concentrations with a bimodal distribution. Causes for the deviations and consequences for the assessment of the vitamin A status of patients under intravenous alimentation are discussed. PMID- 4030064 TI - [Efficacy of early amino acid substitution in gastrectomized patients]. AB - Postaggression metabolism is characterized by decisive, hormone dependent metabolic changes. All reactions are directed with top priority toward ensuring the energy supply. To this end glycogenolysis, gluconeogenesis and lipolysis are increased. Since this reaction of the organism can barely be influenced and it appears to be teleologically purposeful, many authors have repeatedly attempted to achieve a utilization of nutrients as high and economic as possible using an infusion regimen adapted to these conditions. We studied the efficiency of one such adapted nutritional regimen during the first four postoperative days in 10 patients who had undergone gastrectomy. The patients were given 1 g/kg B.W. daily of an amino acid solution adapted to postaggression metabolism, plus 4 g/kg B.W. carbohydrates. We found that clinically relevant parameters such as glucose in serum, triglycerides in serum and pre-albumin could be kept in the reference range. Amino acid homeostasis remained stable under the infusion of the stress adapted amino acid solution. A rise in urea production was not observed. We conclude that good conditions for an economic utilization of the amino acids were created by the infusion regimen selected by us. These results probably can still be optimized by targetted preoperative nutrition with the goal of improving the protein status of such patients already during the preoperative phase. PMID- 4030065 TI - [Continuous measurement of oxygen uptake using the Engstrom Metabolic Computer]. AB - A new system for continuous measurement of oxygen uptake was tested (EMC). Delivered tidal volumes of the system, the accuracy of the oxygen sensor cell, measurement of the oxygen uptake related to different inspiratory oxygen concentrations as well as comparative tests of oxygen uptake according to Fick's principle were studied. Furthermore, we looked for possible leakages in the system. Following to our results even thorough maintenance could not entirely prevent leakages. There was a remarkable increase in measured oxygen uptake if inspiratory oxygen concentration was increased. While carbon-dioxide output was measured at constant levels this led to low respiratory quotients, some of these were less than 0.5. This was caused by a construction error of the system which could be corrected in the meantime. In 70 comparative tests of oxygen uptake between EMC and Fick's principle (measurement of cardiac output and arteriovenous oxygen content difference) we found a mean difference of about 10% (p less than or equal to 0.001) with nearly identical standard deviations. The EMC measured the higher oxygen uptake. Based on our experience the EMC is suitable for continuous measurement of oxygen uptake but it needs good knowledge of the system and the underlying measuring procedures. Additional technical improvements seem to be possible. PMID- 4030066 TI - Avoidance of avascular necrosis of the femoral head, following fractures of the femoral neck, by early reduction and internal fixation. AB - Clinical, experimental and post-mortem studies suggest that avascular necrosis of the femoral head following fractures of the neck of the femur, is due to compression, torsion, stretching or rupture of the blood vessels by displacement of the fragments. If this is true then urgent reduction and internal fixation are important in the prevention of this complication. This study shows that those cases which were submitted to early reduction and internal fixation had a reduced incidence in severity of avascular necrosis compared with those in whom operation was delayed. Therefore it is proposed that fractures of the femoral neck should be treated by early reduction and internal fixation. PMID- 4030067 TI - Infected non-union of a femur treated with a vascularized fibular graft. PMID- 4030068 TI - Accident and emergency content of general surgical workload. AB - In a 12-month period from 1 January to 31 December 1982, 1064 patients were admitted under the care of one consultant general surgeon. Of these, 485 came through the Accident and Emergency (A & E) Department; details of their management are presented. All the data were collected prospectively, stored on microcomputer discs and later analysed. The surgical cases provided adequate material for training but the planning of curricula did not allow all the A & E trainees to be adequately exposed to it. Head injuries accounted for nearly one third of the emergency workload and were well managed, but more children with this diagnosis were admitted than was necessary. About one-quarter of the investigations performed did not contribute usefully to management; adequate discussion between the laboratories and clinicians and the laying-down of written guidelines may reduce the number of unnecessary investigations. A system which enables casualty officers to follow up the patients whom they admit will help trainees to confirm or refute their initial diagnostic impressions, and should be encouraged. A knowledge of the number, type and outcome of treatment of general surgical cases passing through the A & E Department is important in planning curricula and also for allocating resources. PMID- 4030069 TI - Radiolucent plastic in gunshot wounds. AB - We present two patients who suffered a total of three close-range gunshot wounds. In each injury plastic shot-retaining wadding had been carried deep into the tissues but this was not apparent on the initial radiographs. The presence of such plastic wadding must be considered in all such wounds. PMID- 4030070 TI - The mechanics of skull traction calipers. AB - The relationship between the torque applied to the loading screw and the load required to pull off Cone's type of skull traction caliper was established on cadavers. It was found that at a torque of 0.7 Newton metres (Nm), which corresponds to a compressive force of 13 lb (58 N) on the skull, the caliper became detached at the maximum traction load of 60 lb, but still held during this traction load at compressive forces above 18 lb (80 N). Clinically, an instrumented load cell was incorporated into one of the fixing pins on a skull traction caliper and it was found that the compressive load fell on average by 15 per cent over a period of 21 days of traction. Taking into account this fall in load with time and the limiting torque for pull-out with a traction force of 60 lb (265 N) it is suggested, for complete clinical safety, that a compressive load of 20 lb (88 N) obtained at a torque of 0.85 Nm should be applied to the loading screw of a Cone's type of caliper. Using these values in a loading analysis of the securing pins, suggestions are made as to the ideal design of skull traction calipers and the shortcomings of various designs of existing calipers are discussed, in particular the pins' lengths, compressive load and the pins' placement. PMID- 4030071 TI - Haematoma block--a safe method of reducing Colles' fractures. AB - A total of 136 patients required an anaesthetic to enable distal fractures of the forearm to be reduced. There were no significant differences in the numbers requiring remanipulation between the three methods employed: haematoma block, Bier's block or general anaesthesia. The advantages of the haematoma block are discussed. PMID- 4030072 TI - The effect of seat belt legislation on injuries sustained by car occupants. AB - Details are given of the injuries sustained by 402 car drivers, 209 front seat passengers and 147 back seat passengers involved in road accidents during the two 4-month periods before and after the introduction of the compulsory wearing of seat belts on 1 February 1983. Comparisons are made between the injury patterns in those wearing and not wearing seat belts and in back seat passengers. PMID- 4030073 TI - An unusual complication of external cardiac massage. PMID- 4030074 TI - Isolated pancreatic damage following seat belt injury. AB - A case is reported of a 25-year-old male driver who suffered blunt injury to the abdomen by a seat belt at the time of a road traffic accident. The pancreas was the only organ disrupted and this gave rise to traumatic pancreatitis followed by a pseudocyst. The delay in clinical signs is emphasized and the management described. PMID- 4030075 TI - Late jejunal perforation following blunt injury. PMID- 4030076 TI - Traumatic subarachnoid-pleural fistula. PMID- 4030077 TI - Hangman's fracture in ankylosing spondylitis. PMID- 4030078 TI - Fracture of the body of the sternum associated with the use of static seat belts. AB - Four cases of fracture of the body of the sternum associated with the use of a static type of seat belt are reported. We wish to draw attention to an easily missed fracture in patients surviving a road traffic accident. PMID- 4030079 TI - Superior dislocation of the patella. PMID- 4030080 TI - Superior glenohumeral dislocation--a case report. PMID- 4030081 TI - Intraperitoneal foreign bodies passed via the umbilicus. PMID- 4030082 TI - Omental injury in a hernial sac. PMID- 4030083 TI - Dislocation of the superior tibiofibular joint. AB - Derangements of the superior tibiofibular joint are divided into anterolateral, posteromedial and superior dislocations and chronic instability. Two cases of anterolateral dislocation, both needing open reduction, are presented together with a case of posteromedial dislocation. PMID- 4030084 TI - Immediate radial nerve palsy complicating fracture of the shaft of the humerus: when is early exploration justified? AB - A series of 59 patients with immediate complete radial nerve palsy complicating a fracture of the shaft of the humerus was analysed. In 27 patients the radial nerve was explored and the fracture was fixed within 3 weeks of the accident. In 12 other patients exploration was performed after an average of 17 weeks. The remaining 20 patients showed signs of spontaneous recovery within 4 months and were managed conservatively. The mean follow-up time was 3 years. At exploration, laceration, interposition between the fragments or entrapment of the radial nerve in callus was found significantly (P less than 0.01) more often with longitudinal fractures of the distal third (46 per cent) than with transverse fractures of the middle third, in which 85 per cent of the explored cases showed the nerve to be no more than slightly bruised. Useful recovery was seen in 46 patients (78 per cent of the whole series). PMID- 4030085 TI - Pseudo-abusive human bite marks in a Chinese infant. PMID- 4030086 TI - Relationships between levels of lysozyme, lactoferrin, salivary peroxidase, and secretory immunoglobulin A in stimulated parotid saliva. AB - Recent studies suggest that salivary lysozyme (Lz), lactoferrin (Lf), peroxidase (Spx), and secretory immunoglobulin A (sIgA) may interact in a common antimicrobial system. A multiple protein approach therefore may be needed to determine the role of this system in oral health and ecology. In the present study we investigate the relationships between levels of Lz, Lf, Spx, and sIgA (adjusted for flow rate and total protein) in stimulated parotid saliva from 44 dental students. Principal components analysis was used to determine major patterns of intercorrelation between variables; cluster analysis was used to identify groups of subjects with similar salivary profiles for Lz, Lf, Spx, and sIgA. Spx tended to vary independently of Lz and Lf, which, in turn, tended to vary together. sIgA showed a weak negative relationship with Spx and a weak positive relationship with Lz and Lf. Six major clusters of subjects with similar antimicrobial protein profiles were found. These were significantly different at P less than 0.0001. Spx was the most important determinant of cluster membership followed (in order of importance) by Lz, Lf, and sIgA. Cluster profiles were Spx , sIgAmu, Lf-, Lz-; Spx-, sIgA+, Lfmu, Lz+; Spxmu, sIgAmu, Lfmu, Lzmu; Spx+, sIgA , Lf-, Lz-; Spx+, sIgAmu, Lf+, Lz-; and Spx+, sIgAmu, Lf+, Lz+ (-, mu, and + refer to the position of the cluster mean each variable relative to the overall mean for that variable). Results suggest that clusters may be a product of independent variation in the secretory activity of acinar and intercalated duct cells. PMID- 4030087 TI - Detection of the thermostable direct hemolysin gene and related DNA sequences in Vibrio parahaemolyticus and other vibrio species by the DNA colony hybridization test. AB - A specific gene probe for the Vibrio parahaemolyticus thermostable direct hemolysin gene was constructed and used to examine the presence or absence of the thermostable direct hemolysin gene or related DNA sequences in V. parahaemolyticus and other vibrios by the DNA colony hybridization method. The gene probe consisted of a 406-base-pair, completely internal fragment covering 71% of the structural gene with PstI linkers added to the ends. Six copies of this 415-base-pair PstI fragment were cloned into plasmid pBR322, which yielded large amounts of the probe DNA. One hundred forty-one V. parahaemolyticus strains were tested with the gene probe, and the results were compared with those of phenotypic assays for the thermostable direct hemolysin. All Kanagawa phenomenon positive strains were gene positive. However, 86% of the strains that exhibited weak Kanagawa phenomenon and 16% of Kanagawa phenomenon-negative strains also reacted with the gene probe. Immunological methods for the detection of the thermostable direct hemolysin (modified Elek test, enzyme-linked immunosorbent assay) showed better correlation with gene probe results. All gene-positive strains produced hemolysin detectable in the enzyme-linked immunosorbent assay, although occasional strains showed weak reaction. The modified Elek test was slightly less sensitive than the enzyme-linked immunosorbent assay. All gene negative strains were also negative in these immunological assays. One hundred twenty-one strains of Vibrio spp. other than V. parahaemolyticus were tested with the gene probe; only Vibrio hollisae strains reacted with the probe under stringent conditions. PMID- 4030088 TI - Relationship between gingival crevicular fluid and serum antibody titers in young adults with generalized and localized periodontitis. AB - The objective of the present study was to determine the relationship between concentrations of antibodies in serum and those in gingival crevicular fluid (GCF) of patients with juvenile periodontitis and severe periodontitis. Most antigens used to quantitate antibodies were obtained from a panel of bacteria associated with juvenile periodontitis or severe periodontitis. We further investigated variation in antibody titer among different periodontal sites and the extent to which antibody in GCF is locally derived. Titers of antibody, total immunoglobulin G (IgG), and human serum albumin were determined with sensitive radioimmunoassays. The relationship between serum and GCF antibody was complex. Both person-to-person variability and marked variability within the same subject were found among different sites of similar clinical status. The site-to-site variability was found not only for antibody reactive with periodontal organisms, but also for antitetanus toxoid, total IgG, and even human serum albumin. Generally the variability was in the degree of depression of the level in GCF relative to that in serum. However, anti-Bacteroides gingivalis and anti Actinobacillus actinomycetemcomitans in GCF often exceeded the level in serum. When antibody titers in serum and GCF were calculated per milligram of human serum albumin, most of the apparent depressions of antibody in GCF disappeared. The ratio of antibody in serum to that in GCF approached unity for all organisms except B. gingivalis and A. actinomycetemcomitans Y4, which were markedly elevated. Furthermore, the level of IgG per milligram of human serum albumin in GCF was about twice the level in serum. We believe that human serum albumin reflects serum contribution to the GCF, and we therefore attribute the increased level of IgG per milligram of albumin in GCF to local synthesis. It appears that anti-B. gingivalis and anti-A. actinomycetemcomitans represent an important portion of this local antibody synthesis, since most seropositive patients with severe or juvenile periodontitis had at least one site elevated, and the magnitudes of the elevations were large in many sites. Those sites yielding elevated antibody exhibited no obvious differences in clinical parameters of probeable depth or attachment level as compared with sites in which antibody levels in GCF were similar to serum levels. Elevated antibody in GCF may relate to changes in disease activity that are not detectable by usual clinical measures. PMID- 4030089 TI - Bacteroides endodontalis and other black-pigmented Bacteroides species in odontogenic abscesses. AB - Twenty-eight odontogenic abscesses were examined for the presence of black pigmented Bacteroides spp. Of the 28 samples, 26 were found to contain one or more species of black-pigmented Bacteroides. Abscesses were divided into three categories according to the tissue of origin: endodontal, periodontal, and pericoronal. Four abscesses which developed after extraction were also examined. It was found that Bacteroides endodontalis, a newly described species of asaccharolytic black-pigmented Bacteroides, was isolated almost exclusively from periapical abscesses of endodontal origin. B. intermedius proved to be the most frequently isolated species in all of the samples. B. gingivalis was present in all of the periodontal abscesses studied, as well as in two endodontal abscesses. B. melaninogenicus was recovered once from a pericoronal abscess. Precautions for the isolation of B. endodontalis are discussed. PMID- 4030090 TI - Protection of rabbits against experimental pasteurellosis by vaccination with a potassium thiocyanate extract of Pasteurella multocida. AB - Antigens were extracted from a virulent isolate of Pasteurella multocida (serotype 3, 12, 15:D) with potassium thiocyanate, and a vaccine was prepared. Pasteurella-free rabbits were vaccinated intranasally and intraconjuctivally twice with a 2-week interval and challenged intranasally with the homologous P. multocida serotype 2 weeks after the second vaccination. The vaccinated rabbits produced serum immunoglobulin G and nasal mucosal immunoglobulin A against P. multocida. The vaccine protected the challenged rabbits against clinical disease and death; however, otitis media was not prevented, and microscopic inflammatory lesions were occasionally noted in the lungs and nasal turbinates. In contrast, nonvaccinated, challenged rabbits became febrile, dyspnic, depressed, and anorectic, and five of six died within 4 days of challenge with severe lesions including pneumonia, pleuritis, otitis media, and bacteremia. The vaccine prevented death and colonization of challenge organisms in the blood and lung, but did not prevent colonization of the middle ear. The vaccine alone did not cause clinical disease or gross lesions, but did produce microscopic pulmonary inflammatory lesions. PMID- 4030091 TI - Ultrastructural study of ehrlichial organisms in the large colons of ponies infected with Potomac horse fever. AB - Potomac horse fever is characterized by fever, anorexia, leukopenia, profuse watery diarrhea, dehydration, and high mortality. An ultrastructural investigation was made to search for any unusual microorganisms in the digestive system, lymphatic organs, and blood cells of ponies that had developed clinical signs after transfusion with whole blood from horses naturally infected with Potomac horse fever. A consistent finding was the presence of rickettsial organisms in the wall of the intestinal tract of these ponies. The organisms were found mostly in the wall of the large colon, but fewer organisms were found in the small colon, jejunum, and cecum. The organisms were also detected in cultured blood monocytes. In the intestinal wall, many microorganisms were intracytoplasmic in deep glandular epithelial cells and mast cells. Microorganisms were also found in macrophages migrating between glandular epithelial cells in the lamina propria and submucosa. The microorganisms were round, very pleomorphic, and surrounded by a host membrane. They contained fine strands of DNA and ribosomes and were surrounded by double bileaflet membranes. Their ultrastructure was very similar to that of the genus Ehrlichia, a member of the family Rickettsiaceae. The high frequency of detection of the organism in the wall of the intestinal tract, especially in the large colon, indicates the presence of organotrophism in this organism. Infected blood monocytes may be the vehicle for transmission between organs and between animals. The characteristic severe diarrhea may be induced by the organism directly by impairing epithelial cell functions or indirectly by perturbing infected macrophages and mast cells in the intestinal wall or by both. PMID- 4030092 TI - Causative ehrlichial organisms in Potomac horse fever. AB - An ehrlichia was consistently isolated from the peripheral blood leukocyte fraction of ponies that had been experimentally infected with Potomac horse fever by whole blood transfusion from naturally infected horses. The organism was propagated in a human histiocyte cell line for 3 to 5 weeks and then inoculated intravenously or intradermally into healthy adult ponies. Clinical signs of Potomac horse fever, which varied in the degree of severity, occurred 9 to 14 days post-inoculation in all of the ponies. One pony died 20 days post inoculation. The ehrlichial organism was reisolated in the human histiocyte cell line from the blood leukocyte fraction of all of the experimental ponies on each day that samples were examined (days 9, 10, 11, 19, and 39). These organisms were identical to those originally detected in the wall of the intestine of ponies with clinically diagnosed Potomac horse fever when compared by light and electron microscopy and an immunofluorescence labeling technique. The immunofluorescent antibody titer became positive in a pony at 20 days postinjection. These results indicate that the ehrlichial organisms is the causative agent of Potomac horse fever. PMID- 4030093 TI - Quantitative analysis of cell walls of nutritionally variant streptococci grown under various growth conditions. AB - Strains of nutritionally variant streptococci are usually isolated from patients with subacute bacterial endocarditis. Only recently have these strains been subdivided into three serotypes; however, no group-specific antigen has been described. To understand the immunochemical basis for the serology of these microorganisms as well as set the groundwork for adherence studies, quantitative analysis of the cell walls of nutritionally variant streptococci was undertaken. The bacteria were grown in semisynthetic medium or pyridoxal-supplemented Todd Hewitt broth and harvested during the exponential or stationary phase. Cell walls were isolated and analyzed for amino sugars, sugars, polyalcohols, amino acids, and phosphorus by gas chromatography, high-pressure liquid chromatography, or colorimetric assays. The peptidoglycans of the cell walls of the prototype strains from the three serotypes were representative of other streptococcal cell walls, including the presence of alanine as the possible cross-bridge. The composition of the peptidoglycan was similar for all three strains and included a decreased concentration of peptidoglycan in their cell walls during the stationary phase. Glucosamine, glucose, galactose, ribitol, and a small amount of rhamnose were found in each of the cell wall polysaccharides. Galactosamine was only found in serotype II and III cell walls and might be responsible for the previously described cross-reaction between these strains. The concentration of the other sugars and amino sugars varied in each of the cell wall preparations, depending on the growth conditions. Finally, all three strains expressed both ribitol and phosphorus in their cell walls, characteristic of the presence of a ribitol teichoic acid. Therefore the cell wall composition of the nutritionally variant streptococci varies depending on the growth conditions, and their composition appears similar to that of strains of Streptococcus mitis. PMID- 4030094 TI - Immunoglobulin M and immunoglobulin G responses in BALB/c mice to conjugated outer membrane extracts of four Salmonella serotypes. AB - Outer membranes (OMs) of Salmonella enteritidis, S. anatum, S. typhimurium, and S. infantis were extracted and cross-linked with glutaraldehyde to form a large macromolecular antigen. The antigen consisted of OM proteins and lipopolysaccharide and was designated 4-OMP-LPS. Polyacrylamide gel electrophoresis of extracted OMs from each serotype revealed differences in protein profiles. S. enteritidis and S. infantis possessed a greater variety of proteins than did S. anatum and S. typhimurium. Immunizations with 4-OMP-LPS in phosphate-buffered saline (4-OMP-LPS-C) and 4-OMP-LPS emulsified with muramyl dipeptide in the oil phase of a hexadecane-water emulsion (4-OMP-LPS-MDP) revealed that BALB/c mice were capable of eliciting specific primary and secondary immunoglobulin M (IgM) and IgG responses. Both antigen preparations were capable of eliciting IgM and IgG specific for the cell surfaces of each live Salmonella serotype. Also, 4-OMP-LPS-MDP and 4-OMP-LPS-C were capable of evoking a substantial anamnestic response. Adsorption studies revealed that the combined serotypes had the antigenic capacity to adsorb up to 94% of the antibodies, but 4 OMP-LPS-MDP antibodies were more effectively adsorbed than were 4-OMP-LPS-C antibodies. Adsorption of pooled antiserum with heterologous bacteria yielded a variety of adsorption profiles. PMID- 4030095 TI - Identification of chitin as a structural component of Giardia cysts. AB - The intestinal parasite Giardia lamblia is a significant cause of diarrheal disease, which is perpetuated by the infective cyst form of the parasite. Although a rational approach to the control of giardiasis would be to inhibit cyst formation, nothing is known of the chemical composition of the cyst wall or of its biosynthesis. In these studies, we have shown that chitin is a major structural component of G. lamblia and G. muris cyst walls. This conclusion is based on the finding that chitinase specifically destroys the cyst wall, as revealed by electron microscopy. The presence of chitin was also shown directly by lectin binding studies. Of 12 lectins with diverse carbohydrate recognition specificity, only the N-acetylglucosamine-specific lectins wheat germ agglutinin, succinylated wheat germ agglutinin, and tomato lectin bound to cyst walls, as shown by fluorescence microscopy and cytochemistry. Wheat germ agglutinin binding was completely abolished by treatment of the cysts with purified chitinase. This effect was specific since it could be prevented by incubating the enzyme with chitin before treatment of the cysts. Treatment of cysts with N-acetyl-beta glucosaminidase partially inhibited wheat germ agglutinin binding, whereas other glycosidases and proteases had no effect. These findings indicate that chitin is a major structural component of Giardia cyst walls and raise the possibility that inhibitors of chitin synthesis may be of use in preventing encystation and thus controlling spread of the disease. PMID- 4030096 TI - Pyruvate dehydrogenase activity in Streptococcus mutans. AB - Streptococcus mutans NCTC 10449 and Escherichia coli K-12 strain 37 were grown under aerobic and anaerobic conditions. In cell extracts of both strains, pyruvate dehydrogenase activity dependent on thiamine pyrophosphate, coenzyme A, and NAD was shown. The enzyme was induced by pyruvate in the growth medium, and there was higher activity in aerobically grown cells than in anaerobically grown cells. Acetyl phosphate was a potent inhibitor of the activity. This inhibition was partly overcome by inorganic phosphate. PMID- 4030097 TI - An in vitro system to study listericidal capacity of macrophages from separate mice: resident macrophages exhibit different activation patterns. AB - An in vitro system with macrophages from individual mice was established to study their listericidal capacity. Because no antibiotics were used, bacterial killing was really due to macrophages in short-term culture. To restrict the extracellular growth of bacteria, cell culture medium was changed at 1-h intervals. We demonstrated that intracellular growth of listeria in macrophage pools from untreated animals varies considerably. Obviously, preactivated macrophages are constantly present, so that the common procedure of using macrophage pools from several animals is no longer acceptable. In addition, we demonstrated that in vitro mixtures of listeria-immune macrophages of one animal with cells from untreated animals at different ratios exhibit enhanced bacterial killing above a mere additive effect. Consequently, by using macrophages from individual untreated mice, we found that cells of different animals exhibited various activation stages, although unstimulated, inbred specific-pathogen-free mice of the same age, weight, and sex were used. When equal numbers of macrophages from untreated separate animals were mixed in vitro, intracellular growth of listeria was only moderate; that is, the number of preactivated macrophages of the individual animals determined listerial growth in the pooled preparation. Furthermore, we showed that identical doses of phorbol myristate acetate exerted different effects on the listericidal activities of macrophages as a function of their preactivation states. These experiments clearly demonstrate the advantage of using macrophages from individual mice for in vitro studies of macrophage activation. PMID- 4030098 TI - Growth inhibition of Streptococcus mutans by cellular extracts of human intestinal lactic acid bacteria. AB - The in vitro growth of Streptococcus mutans was completely inhibited by water soluble extracts from cells of various intestinal lactic acid bacteria identified as Streptococcus faecium, Streptococcus equinus, Lactobacillus fermentum, and Lactobacillus salivarius. The growth inhibition was dependent on the concentrations of the extracts. In contrast, the extracts did not inhibit the growth of the major indigenous intestinal lactic acid bacteria isolated from humans. These lactic acid bacteria were not acutely toxic in mice. PMID- 4030099 TI - Opsonic requirements for phagocytosis of Legionella micdadei by polymorphonuclear leukocytes. AB - The roles of the classical and alternative pathways of complement activation and of antibody in the phagocytosis of Legionella micdadei by polymorphonuclear leukocytes were studied. Normal serum was treated with the appropriate chelators or with heat to inactivate the classical, alternate, or both pathways of complement activation. Normal and complement-depleted sera with or without antibody were employed as opsonins for L. micdadei in phagocytosis assays. There was no difference in the phagocytosis of L. micdadei promoted by normal serum and either C4-deficient serum or serum in which the classical pathway had been inactivated. Both normal and classical pathway-deficient sera promoted significantly greater phagocytosis than did sera in which the alternate pathway or both the alternate and classical pathways had been inactivated. Thus, polymorphonuclear leukocyte phagocytosis of L. micdadei in the absence of antibody required an intact alternate pathway. Specific antibody partially restored opsonization to sera deficient in the alternate or both complement pathways, but phagocytosis was still significantly less than that with the alternate pathway intact. PMID- 4030101 TI - Vibrio vulnificus resists phagocytosis in the absence of serum opsonins. AB - Invasive disease caused by Vibrio vulnificus may result partially from resistance to phagocytic host defense mechanisms. The present studies show that V. vulnificus resists phagocytosis by murine peritoneal macrophages in the absence of serum opsonins and extracellular bacterial products, apparently through the anti-phagocytic properties of the bacterial surface. PMID- 4030100 TI - Isolation of Staphylococcus aureus clumping factor. AB - Immunochemically identical components were isolated from water-soluble phases of five Staphylococcus aureus strains by affinity chromatography on fibrinogen linked Sepharose 4B. The elution was performed with 1 M MgCl2. The component could be isolated from sonicated preparations of whole cells, cell walls, and extracellular products of S. aureus but not from sonicated preparations of staphylococcal L-forms or from Staphylococcus epidermidis. Investigations of the eluted component by immunoelectrophoresis and Western blot analysis by use of different polyspecific antibodies to S. aureus raised in rabbits revealed only one immunoprecipitate or one band. By means of gel filtration on Sepharose CL 6B and sodium dodecyl sulfate-polyacrylamide gel electrophoresis a molecular mass of 420,000 and 360,000 was found, respectively. Chemical analysis showed a carbohydrate content of about 20% by weight. By crossed immunoelectrophoresis the isolated component was demonstrated to bind to human fibrinogen. The finding that this purified component inhibited the fibrinogen-induced clumping of staphylococci strongly suggests that the component is the S. aureus clumping factor. PMID- 4030102 TI - Assessment of serum antibody patterns and analysis of subgingival microflora of members of a family with a high prevalence of early-onset periodontitis. AB - In a study of members of a large family with a high prevalence of early-onset periodontitis, we sampled the subgingival microflora and characterized 40 isolates from each sample. We surveyed serum samples by enzyme-linked immunosorbent assay for antibodies reacting with any of a panel of 21 periodontal bacteria. The mother and 7 of her 13 children had early-onset periodontitis. Bacteroides gingivalis was not detected in the subgingival flora of any affected or unaffected family member, and Actinobacillus actinomycetemcomitans was isolated from only one affected child. Capnocytophaga ochracea was isolated from five of seven affected children and from none of their normal siblings. We found no significant differences among the floras from family members who had rapidly progressive, juvenile, and prepubertal forms of periodontitis. Elevated levels of serum antibody reacting with one or more of the bacteria tested were found in all family members with disease, but in only one periodontally normal family member. Both children with prepubertal periodontitis had antibodies reacting with C. sputigena, a species not found in their subgingival floras, but with none of the other bacteria tested. All remaining affected family members had antibodies to one or more serotypes of A. actinomycetemcomitans, and four had antibodies reacting with additional bacteria, including C. sputigena, Eikenella corrodens, Fusobacterium nucleatum, and Haemophilus aphrophilus. Sera from patients contained antibodies specific for putative periodontal pathogens not found in their pocket flora, and conversely, putative periodontal pathogens for which no serum antibodies were found frequently comprised a large proportion (10% or more) of the pocket flora. In no case were both the bacterium and its antibody found. These observations are suggestive of sequential infection in the early-onset forms of periodontitis and of induction of protective immunity against reinfection by the same microorganism. PMID- 4030103 TI - Lymphokine activation of J774G8 cells and mouse peritoneal macrophages challenged with Toxoplasma gondii. AB - In vitro activation of macrophage cell line J774G8 and mouse peritoneal macrophages resulted in oxygen-dependent and oxygen-independent killing of intracellular Toxoplasma gondii. Activation was characterized by oxygen-dependent killing detectable by enhanced lysosome fusion and digestion of T. gondii. The toxoplasmacidal activity of activated J774G8 cells and peritoneal macrophages was prevented by adding the oxygen intermediate scavengers catalase or superoxide dismutase during culture. Activated J774G8 cells and peritoneal macrophages also inhibited replication of those Toxoplasma organisms which survived the initial microbicidal activity. The inhibition of Toxoplasma replication was not significantly affected by exogenous catalase or superoxide dismutase. Peritoneal macrophages from Toxoplasma-immune mice showed similar microbicidal and inhibitory responses, supporting the model that activation leads to destruction of intracellular parasites by two different mechanisms. PMID- 4030104 TI - Correlation of plasmid type and disease caused by Coxiella burnetii. AB - The obligate intracellular bacterium Coxiella burnetii is the etiological agent of acute Q-fever and chronic endocarditis in humans and of several zoonotic infections. The DNA from a variety of these disease isolates was compared for homology to the plasmid QpH1, found in the Nine Mile strain. Three patterns of homology were found in these isolates, i.e., one pattern identical to that of QpH1, one common to several endocarditis isolates and goat abortion isolates, and one common to the remaining group of endocarditis isolates. Plasmid DNA from the endocarditis-abortion isolate group, designated QpRS, was mapped by restriction enzyme analysis and compared with QpH1. These data show that QpRS was 2 to 3 kilobase pairs larger, contained DNA not found in QpH1, but was not generated from QpH1 by a single insertional event. Isolation of plasmid DNA from the second endocarditis group of isolates was not successful and may indicate that the plasmid has integrated into the chromosome. This analysis provides the first clear evidence that differences exist between C. burnetii isolates which cause various diseases, indicating that different C. burnetii strains may have unique virulence characteristics. PMID- 4030105 TI - Experimental candidiasis after thermal injury. AB - The ability of Candida albicans to infect thermally injured mice was studied. Female mice were either left unburned or given a 20% total body surface area 2-s or 7-s scald burn. The wound or skin surface was then inoculated with a human burn wound isolate of C. albicans. At 4 h postburn, approximately 10(2) to 10(3) CFU/g of tissue could be recovered from the skin of burned and unburned animals. Unburned mice cleared the organisms from the skin by 72 h, whereas in 7-s-burned animals, the candida increased in numbers to approximately 10(7) CFU/g of tissue. The ability of the organisms to invade systemically after wound surface inoculation was examined in mice given either a 2-s or a 7-s scald burn. Each injury was histologically confirmed as a full-thickness (third degree) burn, with slightly deeper tissue damage observed with the 7-s burn. At each time period examined (1, 4, 7, and 10 days), there were significantly fewer organisms in the wounds of mice given the 2-s injury than in wounds of mice burned for 7 s (P less than 0.05). In 3 of 33 mice given a 7-s injury, organisms were recovered from the kidneys at the time of sacrifice, whereas no evidence of invasion into the kidneys was noted in mice given a 2-s thermal injury. This study demonstrated that thermal injury enhances the ability of C. albicans to infect mice and that the depth of burn appears to be an important factor in determining whether the organisms can invade the burn wound to cause systemic infection. This animal model should be valuable in elucidating the virulence factors of C. albicans that play a role in the pathogenesis of candidiasis after thermal injury. PMID- 4030107 TI - Serum antibodies against common antigens of bacterial lipopolysaccharides in healthy adults and in patients with multiple myeloma. AB - The incidence of infections caused by gram-negative bacteria is increased in patients with multiple myeloma due to secondary humoral immunodeficiency. In order to diagnose patients with increased susceptibility to gram-negative infections, serum antibodies against common determinants of lipopolysaccharides (lipid A and core-polysaccharide) were determined by a rapid enzyme-linked immunosorbent assay (ELISA). It was possible to define a group of patients at high risk of contracting gram-negative infections using this test. Intravenous IgG preparations used as a substitute were shown to contain antibodies against these common antigens. However, it is suggested that the clinically recognized efficacy of these preparations could be due to their containing anti-LPS antibodies. PMID- 4030108 TI - Preliminary study on administration of high-titer lipid A antibody serum in sepsis and septic shock patients. AB - To determine whether sera containing high titers of lipid A antibody may be applicable at effective doses in treating patients with septicemia, a pharmacokinetic study was performed in seven patients aged 24 to 73 years with gram-negative septicemia and various underlying diseases, one of whom received a placebo, and in one patient without infection. In this study, we attempted to determine the effective dosage, the number of infusions and appropriate administration interval for the prevention and treatment of endotoxin shock. Blood samples from each patient were tested for lipid A antibodies before and at regular intervals after administration using an enzyme-linked immunosorbent assay (ELISA). Selected, pooled human immunoglobulin preparations containing high titers (expressed as exponents of 10) of IgG (titer = 3-4) and IgM (titer = 2-4) lipid A antibodies were administered first at a dosage of 8 ml/kg body weight. After administration, the mean lipid A antibody titer increased from 0.4 to 2.3 for IgG and from 2 to 2.4 for IgM. The initial increase was followed by a drop in titer within 24 h, which was perhaps due to antibody consumption. Following the second administration (24 h after the first) of only 4 ml/kg body weight, the mean IgG and IgM titers increased to 2.4 and 3.3, respectively, and dropped slower. A notable increase in circulating lipid A antibody titers was achieved, and four of six treated patients recovered from the sepsis. The two patients who died entered the study in a pre-terminal state. These studies encouraged us to initiate a randomized, double-blind controlled study. PMID- 4030106 TI - 1040 prophylactic infusions with an unmodified intravenous immunoglobulin product causing few side-effects in patients with antibody deficiency syndromes. AB - Thirty-two patients with common variable immunodeficiency (CVID) and two patients with IgA and IgG subclass deficiency received a total of 1,040 intravenous (i.v.) infusions during 60 patient years with 7,575 g of a new immunoglobulin (Ig) preparation. The content of prekallikrein activators and the anti-complementary activity in the tested Ig preparation was low and, in comparison to seven other commercial i.v. Igs, so was the proportion of IgG polymers and fragments. The IgA content was always less than or equal to 0.02 g/l, often less than 0.004 g/l, and it was possible to continuously give the Ig prophylactically to four patients with anti-IgA antibodies, i.e. three with CVID and one with combined IgA-IgG2 deficiency. Adverse reactions were only noted in 4.7% of the 1,040 infusions and in 12 out of the 34 patients. None of the reactions were of the anaphylactic type, but two patients had moderate reactions and one had anuria, probably not caused by the Ig. A simultaneous infection seemed to increase the risk of phlogistic reactions, as five out of six patients who reacted with temperature rise and chills had a simultaneous upper respiratory tract infection. A substudy of various dosage schedules was performed with 11 patients receiving 203 infusions over 10.8 patient years. On 25 mg/kg/week of Ig given i.v. every five weeks, a mean increase in the preinfusion serum IgG level of 0.3 g/l was observed, as compared to earlier i.m. prophylaxis with the same dose. Only 1/4 of the patients on 25 mg/kg/week every five or three weeks reached a preinfusion IgG level greater than or equal to 3 g/l.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4030109 TI - Immune complexes in leptospirosis. PMID- 4030110 TI - Spontaneous adherence of Salmonella typhosa to human peripheral blood lymphocytes in typhoid fever. PMID- 4030111 TI - Serum antibody response to Clostridium difficile toxins in patients with Clostridium difficile diarrhoea. AB - Consecutive serum samples from 61 patients with Clostridium difficile diarrhoea were investigated for antibody response to C. difficile toxins A and B in an indirect enzyme immunoassay (ELISA) and in a neutralization assay against C. difficile cytotoxin. Sera from 64 blood donors, elderly healthy females and patients with other known intestinal enteropathogens served as controls. An immune response was detected by ELISA in approximately half of the patients with C. difficile diarrhoea. The specificity of the ELISA was 94% or 97%, depending on the control material used. Furthermore, a correlation was found between clinical recovery without relapse of C. difficile diarrhoea and high IgG titers to toxin B in the ELISA, and/or appearance of neutralizing antibodies. It is concluded that the ELISA for detection of serum antibodies to C. difficile toxins may be of diagnostic value in combination with the conventional tissue culture assay for cytotoxin in stool. High ELISA IgG titres to toxin B and/or the appearance of neutralizing antibodies may also be a positive prognostic sign in patients with C. difficile diarrhoea. PMID- 4030112 TI - Differential diagnosis of equine respiratory noises. PMID- 4030113 TI - Control of the breeding season in sheep and goats. PMID- 4030114 TI - Data recording in general practice. PMID- 4030115 TI - Effects of acute exposure to increased levels of background industrial noise on cigarette smoking behavior. AB - Automated objective measures of cigarette smoking behavior were recorded while research subjects performed a visual monitoring monetary reinforced operant task. Subjects were required to wear headphones during all sessions. During baseline sessions, subjects were exposed to 60 decibels (dB) of background noise. During experimental sessions, subjects were exposed to 70, 80, or 90 dB of tape-recorded industrial noise via the headphones. Following stabilization of cigarette puffing across sessions, subjects were exposed to different dB levels of industrial noise acutely for one session. Results indicated that increasing dB levels of industrial noise exposure resulted in increased cigarette smoking behavior. PMID- 4030116 TI - Occupational exposure to toluene: neurotoxic effects with special emphasis on drinking habits. AB - Neurotoxic effects of toluene were examined in 43 male rotogravure printers exposed to toluene (age 27-63, mean 41 years; duration of exposure 11-40, mean 22 years) and 31 male offset printers of the same age with slight exposure to aliphatic hydrocarbons. A neurological examination, tests for autonomic nervous function, electroencephalography, psychological tests and computerized tomography of the brain were carried out in addition to a standardized interview. Exposure levels were evaluated for each person separately on the basis of his work history and the results of an earlier study on exposure levels at the same printing shops. Besides a thorough history of alcohol consumption, information about the printers' drinking habits was obtained from the occupational health care centers of the printing shops. The examinations found only slight abnormalities, and there were no statistically significant group differences in the prevalences of abnormalities. No correlations between the abnormalities and the exposure indices were found either. One of the retired workers, however, who had been exposed to high toluene concentrations for over 40 years, had been diagnosed as having chronic organic solvent intoxication. Heavy drinkers of alcohol were clearly more common in the toluene-exposed group. This study detected no clinically significant abnormalities attributable to toluene alone among workers exposed to 68-185 ppm (mean 117) of toluene for over 10 years. The connection between alcohol consumption and toluene exposure is interesting and deserves further study. PMID- 4030117 TI - Immunological and respiratory changes in tea workers. AB - Immunological status and respiratory function were studied in 26 female nonsmokers employed in processing different types of tea. Skin tests with tea allergens demonstrated the highest percentage of positive reaction to sage (45%), gruzyan (40%), mentha (35%), and dog rose (10%). Among 17 skin-tested control workers, 23% had positive skin reaction to sage, 19% to gruzyan tea, 20% to mentha and 11% to dog rose and Indian teas. Serum levels of total IgE were increased in 27% of the tea workers and in 7% of the control subjects. Prevalence of almost all chronic respiratory symptoms was higher in tea workers with positive skin tests than in those with negative skin tests to tea allergens. Tea workers with positive skin tests to tea allergens had larger mean acute reduction over the Monday workshift in flow rates (MEF50%: -11.9%; MEF25%: -20.6%) than in those with negative skin tests (MEF50%: -5.7%; MEF25%: -16.7%), thus suggesting an obstructive effect mostly located in smaller airways. Bronchoprovocation testing with different tea allergens provoked acute reductions of ventilatory capacity in four out of six subjects tested. Relative fall over a 90-min post exposure was greater in MEF25% (ranging from 13% to 67%) than in MEF 50% (ranging from 9% to 45% of the control values). PMID- 4030118 TI - Exposure to fluorotrichloromethane (R-11). AB - Three volunteers were exposed to fluorotrichloromethane (R-11) under experimental conditions. Solvent levels in ambient and alveolar air, in blood and urine were measured. The mean concentration of R-11 in ambient air was 657 ml/m3. The average values of pulmonary retention and solvent levels in alveolar air and blood were 18.2%; 537 ml/m3 and 2.8 mg/l. Inter-individual variations of these parameters are negligible. R-11 concentrations in urine--in contrast to blood or alveolar air--depend on the dose taken up. After termination of exposure, R-11 concentrations in alveolar air and in blood are excreted with biological half lives of seven and eleven minutes respectively during the first phase of elimination and with 1.8 and 1.0 h respectively during the second phase of elimination. Though ambient monitoring should, in most cases, be sufficient for the prevention of occupational diseases, the R-11 concentration in alveolar air seems to be the best parameter if biological monitoring seems to be necessary. PMID- 4030120 TI - Anaphylactoid reactions in anesthesia. PMID- 4030119 TI - The clinical presentation of anaphylactoid reactions in anesthesia. PMID- 4030121 TI - Adverse reactions to protamine. AB - Adverse responses to protamine are most likely multifactorial in nature. Mechanisms include immune-mediated anaphylaxis, complement-mediated and non complement-mediated anaphylactoid reactions, and catastrophic pulmonary vasoconstriction. Some patients may be at higher risk for an adverse reaction to protamine. Whereas patient historical data may influence the decision to administer protamine, once administration is decided on all patients should receive protamine in a cautious manner. Rechallenge may be hazardous, but has occurred without problem in some patients. PMID- 4030122 TI - Allergic and pseudoallergic mechanisms in anesthesia. PMID- 4030123 TI - Anaphylactoid reactions to radiocontrast materials. PMID- 4030124 TI - A monoclonal antibody-based radioimmunoassay for the in vitro production of IgE by lymphocyte cultures. AB - Very sensitive radioimmunoassay systems have been described for the measurement of IgE produced in cultures of human peripheral blood mononuclear cells. However, differing results have been reported when cultures from non-atopic donors are stimulated with pokeweed mitogen, which may be due to cross-reactivity of anti IgE antibodies with IgG. A monoclonal antibody specific for the Fc region of human IgE, and two polyclonal affinity-purified antibodies to IgE were tested for binding to 125I-labelled IgE myeloma proteins and polyclonal IgG in a sensitive double antibody precipitation assay. The monoclonal antibody and one of the polyclonal antibodies bound only IgE, whereas the other polyclonal antibody bound a significant proportion of labelled IgG. A solid phase radioimmunoassay was developed which combined the specificity of the monoclonal antibody with the sensitivity of the first polyclonal antibody as radioactive tracer. A second assay system was also tested using the cross-reacting antibody as tracer. Supernatants of pokeweed mitogen-stimulated peripheral blood mononuclear cell cultures from non-atopic donors were examined for IgE synthesis using both assays. The assay based on the monoclonal antibody did not detect IgE synthesis, whilst the second assay, based on the cross-reacting antibody indicated that spurious IgE had been produced in the same cultures. This study shows that protein-binding assays provide a simple means for checking the specificity of antibodies in solid phase radioimmunoassays, and confirms that pokeweed mitogen does not stimulate IgE production by cells from non-atopic donors when measured by a specific radioimmunoassay. PMID- 4030125 TI - C56 formation in the reaction mixture of isolated complement components through the classical complement pathway. AB - The mechanism of hemolysis of unsensitized erythrocytes by a mixture of 9 isolated, human-derived complement components, C1s, C4, C2, C3, C5, C6, C7, C8 and C9 (C1s-C9) was studied. Of the tested erythrocytes, guinea pig erythrocytes (Egp) were the most susceptible to lysis by C1s-C9, followed by human and sheep erythrocytes. Contamination of the isolated complement components by C56 was ruled out. It was determined that a factor was generated in the reaction mixture of C1s, C4, C2, C3, C5 and C6 (C1s-C6), which had lytic activity against Egp when C7, C8 and C9 were added. We found that the lytic factor was similar to C56 in the following properties: (1) the activity of the lytic factor decreased when incubated with isolated C7 prior to its reaction with Egp; (2) the lytic factor did not bind to Egp by itself but it did bind in the presence of C7; (3) EDTA did not have any inhibitory effect on the lytic factor; (4) the activity of the lytic factor decreased by treatment with anti-C5 and anti-C6 but not by treatment with anti-C3 and anti-C4, and (5) gel filtration of the reaction mixture (C1s-C6) indicated that the elution volumes of the lytic factor and of isolated C56 were similar. Thus, it is likely that C56 is generated in the reaction mixture of C1s C6 and the lytic factor binds to unsensitized erythrocytes together with C7, to form an intermediate EC567 which is susceptible to lysis by the action of C8 and C9. PMID- 4030126 TI - Leukocyte membrane receptors in meningitis and other bacterial infections. AB - Blood leukocytes from 37 patients with acute bacterial infections, and cerebrospinal fluid (CSF) granulocytes from 12 patients with bacterial meningitis, were examined for the distribution of membrane receptors (R) for (1) untreated sheep erythrocytes (E), (2) the Fc portion of IgG (Fc gamma), and (3) complement component C3b. We found a decreased percentage of granulocytes bearing Fc gamma-R in the CSF from patients with meningitis, and in blood from patients with respiratory tract infections. This group also had a decreased percentage of C3b-R bearing granulocytes on admission, whereas meningitis patients had lower levels of C3b-R and Fc gamma-R bearing granulocytes in the 2nd and 3rd week and even later. Several patients with meningitis and gastroenteritis had granulocytes bearing the E-R, previously considered specific for T lymphocytes. Such cells were also found in the CSF. Meningitis and respiratory tract infections were associated with a decreased percentage of 'active' T lymphocytes. The total percentage of T lymphocytes was also decreased in meningitis. Conversely the proportion of Fc gamma-R bearing lymphocytes (consisting mostly of B lymphocytes) was increased in most infections. During the first 3 weeks of bacterial meningitis, the percentages of Fc gamma- and C3b-R bearing granulocytes, and of Fc gamma-R bearing lymphocytes, gradually decreased, while the T lymphocyte percentage increased from the initial low values. PMID- 4030127 TI - Goblet cell number in the nasal mucosa relates to cell-mediated immunity in patients with antibody deficiency syndromes. AB - Histopathological changes in the nasal mucosa were studied in biopsies from the inferior turbinate in 22 patients with common variable immunodeficiency (CVID) and 16 patients with selective IgA deficiency. Most patients with CVID had fewer goblet cells than the healthy controls (p less than 0.001), whereas patients with selective IgA deficiency often had manyfold increased numbers (p less than 0.001). The number of goblet cells showed a significant (p less than 0.001) relationship to the cell-mediated immune function. Patients with lowered cell mediated immune function, as measured by in vivo and in vitro tests, showed reduced numbers or lack of goblet cells. These patients had an increased number of subepithelial, seromucous gland acini compared with healthy controls (p less than 0.01) and patients with selective IgA deficiency (p less than 0.05). The production of mucus may be a compensatory mechanism, participating in the protection of the mucosal surface of the antibody-deficient patient. The increase in the number of goblet cells, but not of subepithelial, seromucous gland acini seems dependent on the cell-mediated immune system. PMID- 4030128 TI - Continuous arteriovenous hemodialysis. PMID- 4030129 TI - Bicarbonate-buffered peritoneal dialysis. PMID- 4030130 TI - Ultraviolet light as a sterilising agent for extracorporeal fluid tubing connectors. PMID- 4030131 TI - A new hemodialysis monitoring device using filtrate concentrations: a comparison with standard serum techniques. AB - A new device allowing sampling to be performed at any time, and using the filtrate obtained during hemodialysis is described. The device was used in 27 patients undergoing regular dialysis. Urea, creatinine and potassium were measured in samples taken both from arterial blood and from the device at 10, 40, 120 and 230 minutes after the beginning of the dialysis. The results were compared. A constant bias of about 10% was noted between the two sets of results but statistical analysis showed this was correctable. PMID- 4030132 TI - Amino acid absorption of plasmapheresed serum by resins and charcoal. AB - The amino acid absorption capacity of two types of charcoal and six forms of ion exchange resin has been assessed. To plasmapheresed serum obtained from human donors amino acids were added to stimulate the levels seen in hepatic failure. This was passed through columns of either resin or charcoal over three hours. The amino acid absorption was estimated. Charcoal consistently removed greater amounts of essential amino acids than resin. None of the ion exchange resins were found to be effective in amino acid absorption. PMID- 4030133 TI - Adverse effects secondary to the treatment with plasma exchange. AB - Side effects and their relationship with the material used were analyzed in 748 plasma exchanges (PE) performed in 75 patients. The total incidence of acute and mild adverse effects (chills and/or fever, paraesthesias, allergic reactions, acute anaemia, vasovagal reactions, abdominal pain and hypotension) was 18.04%. Two patients developed an episode of left cardiac insufficiency. One patient in whom all PE were performed with fresh frozen plasma (FFP) developed metabolic alkalosis. Three patients developed sepsis during treatment with repeated PE and immunosuppressive drugs; in these three patients a permanent vascular inlet was used (shunt or catheter). All patients in whom only FFP was used as replacement solution developed non-A, non-B hepatitis. Neither haemorrhagic nor thrombotic episodes were observed in these patients. It is of the greatest importance to choose the most suitable material for each patient and to develop a careful technique in order to avoid these complications during treatment with PE. PMID- 4030134 TI - Short and long-term clinical effects of plasma-exchange in 33 cases of myasthenia gravis. AB - The authors examine the results of plasma exchange (PE) treatment in 33 patients with myasthenia gravis, who underwent a total of 49 cycles of treatment. On the basis of clinical response, evaluated in relation to a modification of the functional state and to the duration of improvement after PE, we selected a group of 20 responsive patients ("responders" = 60.6%) and 13 non-responsive patients ("non-responders" = 39.4%). Positive effects, some only short-lasting, were observed in 24 patients (72.7%) after 32 cycles of a total of 49 cycles (65.3%). Out of the 11 most critical patients, 7 (63.6%) were considered responders, given the importance and duration of the improvement they presented, while 2 other patients had clear but short-lasting improvements; in these 9 patients, the positive effects amounted to 81.2%. Factors presumably responsible for therapeutic failure in the non-responders are discussed. PMID- 4030135 TI - Henoch-Schonlein purpura with severe ileal involvement responding to plasmapheresis. PMID- 4030136 TI - Diet and cancer of the stomach: a case-control study in Greece. AB - A case-control study focusing on the role of diet in the etiology of gastric cancer was undertaken in Piraeus, the sister city of Athens, in a population characterized by ethnic homogeneity but substantial heterogeneity with respect to dietary habits. The case series consisted of 110 consecutive patients with histologically confirmed adenocarcinoma of the stomach, admitted to two teaching hospitals during a 3-year period; the control series consisted of orthopedic patients admitted to a nearby hospital for accidents, fractures and other orthopedic disorders, during the same time period. Dietary histories concerning the frequency of consumption (per month or per week) of about 80 food items were obtained by the same interviewer. Cases reported significantly less frequent consumption of lemons, oranges, brown bread, and raw, salad-type vegetables (particularly lettuce, onions and cucumbers) and, independently, significantly more frequent consumption of pasta, beans and nuts. A relative risk of about 40 was found between extreme quintiles when the above 9 food items were combined in a linear risk score. Use of an index constructed from the study material will clearly overestimate the level of risk between the extreme quintiles, but nevertheless the risk differences appear noteworthy, and consistent with the international variation in the incidence of gastric cancer. No significant associations were found with alcoholic beverages, coffee or tea. PMID- 4030137 TI - A pilot beta-carotene intervention trial with Inuits using smokeless tobacco. AB - The frequency of exfoliated cells with micronuclei (MNC) was used to estimate the genotoxic effect of smokeless tobacco (snuff) on the oral mucosa and to follow the response to the administration of beta-carotene (180 mg/week, given twice weekly in 6 capsules of 30 mg each). The pilot trial was carried out with Inuits in Gjoa Haven, Northwest Territories, Canada. Their traditional diet, which is rich in caribou and seal meat and liver but low in vegetables and fruits, leads to "normal" serum levels of retinol (447 ng/ml in non-users of tobacco and 463 ng/ml in tobacco users) but low levels of beta-carotene (57 ng/ml for non-users of tobacco and 47 ng/ml for users). Prior to the twice-weekly administration of beta-carotene, the frequency of MNC was 1.87% +/- 0.92 (n = 23) in the mucosa of the lower gingival groove where the tobacco was usually kept. It decreased significantly (P less than 0.001) to 0.74% +/- 0.42 following the 10-week oral administration of beta-carotene capsules. The frequency of MNC did not change significantly in the group receiving a placebo and in snuff users who received no treatment over the 10-week trial period. The size and morphological appearance of the typical snuff-related, whitish, wrinkled patches of the mucosa where the tobacco was kept was not affected by the 10-week treatment with beta-carotene. Similarly, no reduction was observed in the frequency of anucleated, exfoliated mucosa cells. Beta-carotene appears to be an efficient inhibitor of MNC in the oral mucosa of snuff users who do not suffer from any vitamin A deficiency and who have "normal" levels of retinol. PMID- 4030138 TI - Correlation between ganglioside distribution and histological grading of human astrocytomas. AB - Changes in membrane lipid content and composition have been repeatedly detected in experimentally induced as well as spontaneous tumors. Previous data on ganglioside analysis in human astrocytomas suggested a possible correlation between their content and pattern and the histological grading of these tumors. In our study we could definitely prove this correlation: in fact the level of malignancy, passing from grade I to grade IV, is associated with a statistically significant increase of a ganglioside identified as ganglioside GD3. Another important modification in the ganglioside pattern of human astrocytomas is the decrease in polysialylated species with increasing level of malignancy. PMID- 4030139 TI - Purification and partial amino acid sequence of rabbit tumor necrosis factor. AB - Good production of tumor necrosis factor (TNF) in the rabbit was obtained using Propionibacterium acnes IID 912 as a priming agent and subsequent administration of lipopolysaccharide. The physicochemical characteristics of rabbit TNF were very similar to those of murine TNF. The molecular weight of rabbit TNF was 39,000 as estimated by gel filtration, and 18,000 by SDS-PAGE. The isoelectric point was determined as pH 4.0 by isoelectric focusing. Rabbit TNF was stable within the pH range of 5.5 to 11.0, and was stable at 56 degrees C for 8 hr. It was digested by trypsin, pancreatic protease and elastase, but was resistant to neuraminidase. The amino acid sequence of rabbit TNF was determined as Ser-Ala Ser-Arg-Ala-Leu- .... Monoclonal antibody against rabbit TNF completely inhibited both the in vivo and in vitro activity of rabbit TNF. However, this antibody could not inhibit the action of murine TNF. Antitumor activity of rabbit TNF was shown against murine and human cancer cells in vivo and in vitro, and rabbit TNF was also capable of distinguishing malignant cells from normal cells. PMID- 4030140 TI - Heat-resistant mutants of B-16 melanoma cells. I. Stepwise heating in vitro induces progressive increase in resistance to heat. AB - Cloned lines from 4 different families of B-16 melanoma cells were heated repeatedly in tissue culture at 45 degrees C with step-up time intervals. These lines included the partially heat-resistant lines previously selected at 43 degrees C(HR 43 degrees) from wheat-germ-agglutinin-resistant mutant (WGAR, HR43 degrees), concanavalin-resistant mutant (conR-HR 43 degrees), ricin-resistant mutant (ricinR, HR 43 degrees), and parental B-16 (B-16, HR 43 degrees) cells. The heating cycles were repeated 7 to 11 times at 45 degrees C increasing from 45 min to 150 min with 3 weeks of culturing at 37 degrees C between cycles. Heat resistance in most cases increased progressively with each heating step. An extensive library of mutants was thus generated, varying in the degree of heat resistance and the apparent stability. HR variants from the WGAR family appeared to be the most resistant and the most stable. The heat-resistant phenotype was expressed not only by increased survival after a normally lethal heat dose, but also by protection against heat-mediated suppression of proteins and DNA syntheses. Protein synthesis in the heat-resistant cells was not only less suppressed by heat shock, but also recovered more rapidly after removal of shock. Clinical implications of these results and the potential usefulness of the mutant lines for genetic studies are discussed. PMID- 4030141 TI - Mechanisms of human cell neoplastic transformation: relationship of specific abnormal clone formation to prolonged lifespan in X-irradiated human diploid fibroblasts. AB - A total of 9 control and 46 X-irradiated human fibroblast cultures were followed throughout their lifespan in vitro; G-banded karyotypes were examined at regular intervals. The lifespan (mean population doublings) of irradiated cultures was slightly but significantly prolonged over that of controls. None of the cultures developed any changes in cell morphology characteristic of neoplastic transformation. A number of abnormal clones containing marker chromosomes emerged in the irradiated cultures. Most of these senesced early, but 2 clones were associated with a considerably increased lifespan. One of these had a deletion in the short arm of chromosome I (p22, p32), and the other had 2 specific translocations involving chromosome 22, t(1;22)(q25,q12) and t(6;22)(p22,q11). We hypothesize that the emergence of an abnormal clone with translocations in the vicinity of critical oncogenes may be associated with prolongation of lifespan and the induction of immortalization in human diploid cells, an event independent of the acquisition of other characteristics of the transformed phenotype. PMID- 4030142 TI - Analysis of page utilization and types of articles published in four major American cardiology journals in 1984. AB - Several peer-review journals devoted exclusively to cardiology are published in the U.S.A. Although the types of articles and the authors of (and reviewers for) the articles in the various American cardiologic journals are similar, the numbers of articles and pages utilized for them in the various journals are quite different. This article summarizes the results of counting the numbers of editorial (non-advertising) pages published and the types of articles published during 1984 in the American Heart Journal, the American Journal of Cardiology, Circulation, and the Journal of the American College of Cardiology. PMID- 4030143 TI - The surface measurement of aortic atherosclerosis: critical survey and comparison with histologic findings. AB - Both the reproducibility of the surface measurements of aortic atherosclerosis and the agreement between gross inspective and histologic changes were evaluated. Aortas from male broad breasted white turkeys were chosen because of the high incidence of spontaneous and typical atherosclerotic lesions in this animal strain. Ten male turkeys were killed at 33 weeks of age. The aortas were removed including the iliac bifurcation and stained with Sudan III. Each aorta was processed blindly by four pathologists and a computerized planimeter to determine normal areas, sudanophilic areas and areas covered by plaques. The analysis of variance showed significant differences among the four pathologists' measurements of sudanophilic areas (P less than 0.01) and areas covered by plaques (P less than 0.001). The coefficients of variation among the four determinations made by one pathologist on the same aorta were 3.6% for total aortic area; 10.08% for sudanophilic area; 47.6% for the area covered by plaques. On each aorta histology was performed at the level where all the four pathologists recorded the same findings at inspection, namely a normal area, a sudanophilic area, and an area covered by plaques. Important discrepancies occurred between findings at inspection and those of histologic examination: the ten areas classified as "normal" by all the four pathologists at inspection were shown at histologic examination to be normal in only two cases. In one case a musculo-elastic layer and in seven cases a fibro-elastic layer were found. The ten areas classified as "sudanophilic" by all the observers showed a fibro-elastic layer in five cases, a musculo-elastic layer in two cases and normal findings in three cases. The ten areas classified as "covered by plaques" displayed a typical atherosclerotic plaque in all cases but one. In conclusion, our data indicate that the reproducibility of gross inspective methods is low. Important discrepancies exist between findings at inspection and histologic examinations. The relevance of these findings remains to be established as far as the assessment of human atherosclerosis is concerned. PMID- 4030144 TI - Coarctation and related aortic arch anomalies in hypoplastic left heart syndrome. AB - The aortic arches of 34 specimens with hypoplastic left heart syndrome were studied in order to establish the frequency, the nature and the clinical implications of aortic arch anomalies. A localized aortic coarctation was present in 23 specimens. The coarcation was located preductally in 2 and paraductally in 21 cases. The degree of obstruction caused by the coarctation varied considerably. In only 6 cases (1 preductal and 5 paraductal) was the obstruction judged to be severe. One of these cases had an additional aneurysm of the aortic wall proximal to the coarctation. An aberrant relation of the ductus arteriosus and the aortic arch was found in 2 specimens without localized coarctation. In the remaining 9 specimens the aortic arch appeared normal. The aortic arch anomalies were mostly present in specimens with a severely hypoplastic ascending aorta. Clinicians, when preparing infants with hypoplastic left heart syndrome for surgical palliation, should always suspect associated aortic arch anomalies, especially when there is severe hypoplasia of the ascending aorta. Coarctation of the aorta will require additional surgical treatment. PMID- 4030145 TI - Left ventricular diastolic filling in patients with left ventricular dysfunction. AB - The pattern of abnormal left ventricular diastolic filling and its specificity in coronary disease patients with severe left ventricular dysfunction has received little attention. We evaluated the left ventricular diastolic filling curve derived from gated blood pool scans in 21 normals, 61 coronary disease patients with ejection fractions less than or equal to 30%, and 51 congestive cardiomyopathy patients with ejection fraction less than or equal to 30%. The peak filling rate (PFR), peak ejection rate (PER), PFR/PER and the % stroke volume filled at 1/3 of diastole (%SV-1/3 DT) and at the end of the rapid filling period (%SV-RFP) were determined for each group. The PFR and PER were reduced in both coronary disease and congestive cardiomyopathy groups. The PFR/PER was increased in the coronary disease group (1.19 +/- 0.28) and congestive cardiomyopathy group (1.21 +/- 0.32) as compared to normals (0.93 +/- 0.20, P less than 0.001). A greater %SV-1/3 DT and %SV-RFP were noted in both coronary disease and congestive cardiomyopathy groups. Coronary disease and congestive cardiomyopathy patients with a mean pulmonary capillary pressure (PCP) greater than or equal to 18 mm Hg had a greater PFR/PER, %SV-1/3 DT, and %SV-RFP than patients with a PCP less than 18 mm Hg. An abnormal and nonspecific pattern of left ventricular diastolic filling is present in both coronary disease and congestive cardiomyopathy patients and is characterized by an increased PFR/PER, a greater %SV-1/3 DT, and a greater %SV-RFP. This pattern may be related to elevated PCPs. PMID- 4030146 TI - Effects of pharmacologic autonomic blockade on atrial electrophysiologic properties in normal subjects and in patients with sinus node disease. AB - In order to elucidate the influence of autonomic nervous system on atrial electrophysiologic properties, we studied 10 patients with sinus node dysfunction and 10 age-matched normal subjects. In each of them effective and functional refractory periods of the right atrium (near its junction with the superior caval vein) were measured, during atrial pacing (100/min) and using variable current strengths (2, 3, 4, 5, 7, 10, and 15 mA), before and after pharmacologic autonomic blockade (using intravenous propranolol 0.2 mg/kg and atropine 0.04 mg/kg). Mean values of effective and functional refractory periods at each current strength were significantly higher in patients with sinus node disease than in normal subjects both before and after autonomic blockade. Blockade did not significantly modify mean values of effective and functional refractory periods at any current strength, either in patients with sinus node disease or in normal subjects. Furthermore, autonomic blockade did not change the effects of the increase of current strength on atrial refractoriness in either group. We conclude that our data indicate a prolonged refractoriness to be present in patients with sinus node disease even in the absence of influences from the autonomic nervous system. Thus, we can suggest a "primary" involvement of atrial fibers in this pathophysiological condition. Propranolol together with atropine did not induce changes of atrial refractoriness. Indeed, they probably exerted an opposite effect. The effects of the increase of current strength on atrial excitability do not seem to be mediated by autonomic humoral agents. PMID- 4030147 TI - Type A behavior and myocardial infarction. A 9.5-year follow-up of a small cohort. AB - To test the hypothesis that type A behavior is associated with the incidence of myocardial infarction in groups outside the U.S.A., 243 healthy males, aged 45-59 years, who participated in the Kaunas-Rotterdam Intervention Study (KRIS) were interviewed and followed for 91/2 years. No association between type A behavior and the incidence of all coronary events (myocardial infarction and cardiac death) was found. Fatal coronary events, however, were found to have occurred in types A only (P = 0.04). This weak, but positive association indicates that in Europe too the incidence of fatal coronary heart disease is associated with type A behavior. PMID- 4030148 TI - Assessment of dysfunction in aortic regurgitation by stress-shortening relationship. AB - Some patients with aortic regurgitation develop irreversible left ventricular dysfunction. The purpose of this study was to noninvasively examine left ventricular function in patients with aortic regurgitation by determining the end systolic stress-shortening relationship using M-mode echocardiography. Ten normal volunteers and 10 patients with chronic, isolated aortic regurgitation were studied at rest and following load and inotropic alteration by cold pressor testing. The baseline ejection phase indices of ejection fraction and percent fractional shortening did not distinguish between normals and patients with aortic regurgitation (74.6% +/- 2.8% versus 67.0% +/- 4.2%, P = NS and 37.6% +/- 2.4% versus 31.6% +/- 2.7%, P = NS, respectively.) End-systolic stress was significantly greater in patients with aortic regurgitation both at rest (107.8 +/- 11.6 dynes/cm2 X 10(-3) versus 68.4 +/- 4.8 dynes/cm2 X 10(-3), P less than 0.005) and after cold pressor intervention (122.8 +/- 13.0 dynes/cm2 X 10(-3) versus 80.1 +/- 4.0 dynes/cm2 X 10(-3), P less than 0.005). Normals showed increased fractional shortening in the presence of increasing end-systolic stress. Patients with aortic regurgitation showed decreased fractional shortening during increased stress. This response suggests either left ventricular dysfunction with increasing stress or decreased myocardial contractile reserve after cold pressor inotropic stimulation. End-systolic stress-percent fractional shortening relationship may be a sensitive indicator of early left ventricular dysfunction in patients with aortic regurgitation. PMID- 4030149 TI - Alcohol and ischemic heart disease: wine, beer or both? AB - The relationship between mortality from ischemic heart disease and alcoholic beverage consumption in 27 countries was investigated. A significant inverse correlation was obtained between mortality due to ischemic disease and percent contribution to alcohol consumption by wine (r = -0.75, P less than 0.001). A positive correlation (r = 0.60, P less than 0.001) was obtained between ischemic heart disease and alcohol consumption from beer. PMID- 4030150 TI - Fatal cerebral edema following angiocardiography: a case report. AB - We describe a case of fatal reaction to angiocardiography following investigation of tetralogy of Fallot. This happening has occurred only once in 8300 procedures in our laboratory. It was due to cerebral edema. Although a recognized, but very rare, hazard following injection of contrast material, we found no way in our case of either predicting the outcome or its possible recurrence. PMID- 4030151 TI - Indirect versus direct hypnotic suggestions--an initial investigation: a brief communication. PMID- 4030152 TI - Hypnotic age regression and the importance of assessing interpersonally relevant affect. PMID- 4030153 TI - Iconic memory and hypnotizability: processing speed, skill, or strategy differences? PMID- 4030154 TI - The response criterion problem in tests of hypnosis and memory. PMID- 4030155 TI - Hypnotic susceptibility, hypnosis, and EMG biofeedback in the reduction of frontalis muscle tension. PMID- 4030156 TI - Hypnosis as an adjunct to the psychotherapy of the severely disturbed patient: an affective development approach. PMID- 4030157 TI - Role-played and hypnotically induced simulation of psychopathology on the MMPI: a partial replication. PMID- 4030158 TI - An empirical evaluation of the neurolinguistic programming model. PMID- 4030159 TI - Althesin in high risk patients with heart disease in orthopedic surgery. AB - Althesin was used in 65 patients with heart diseases undergoing orthopedic surgery, alone or in association with neuroleptanalgesic drugs. Patients were classified according to four types of heart diseases: atrial fibrillation in older patients (41.53%), disorders of cardiac rhythm (23.07%), valvular diseases (9.23%), ischemic heart disease (26.15%) and according to the degree of risk (ASA 3 and 4). All patients were carefully studied before the operation, and adequately treated with cardiac drugs in order to reduce heart rate, to reduce blood pressure and to reduce heart failure, whenever necessary. Anesthesia was induced with Althesin in all patients, and maintained with Althesin/N2O/O2 in 24.61% of the cases, and Althesin/N2O/O2/NLA in 75.39% of the cases. No significant changes in heart rate or in blood pressure were observed either during surgery or in the first 24 hours after the operation. There were five deaths in the days after the operation, one of which was due to surgery. One patient was discharged while still in a coma. All the other patients were discharged from the hospital within approximately four weeks from the day of the operation in good general condition. It was concluded that Althesin is a very reliable anesthetic agent for patients with heart diseases. PMID- 4030160 TI - The "status quo" of clinical pharmacology in Japan. AB - The status quo in the educational system of Japanese medical schools and the status quo and tomorrow in Clinical Pharmacology is described, analyzed and interpreted. All relevant criteria are considered and the stipulations are discussed which are very important for the clinical pharmacologist. The importance of clinical pharmacology in the curriculum is proved as a conditio sine qua non. PMID- 4030161 TI - Pharmacokinetics and pharmacodynamics of three sustained-release theophylline preparations (Theograd, 350 mg Theolair Retard, and 300 mg Theolin Retard) in steady state in six normals and six patients with chronic asthmatic bronchitis- Part II: Lung function. AB - The lung function profiles of a group of six healthy volunteers and six patients with moderately severe asthmatic bronchitis were compared after one theophylline infusion and after oral administration of Theograd (350 mg), Theolair Retard (350 mg), and Theolin Retard (300 mg) all given twice daily for 1 week. The group of patients showed a good reversibility of bronchoconstriction after intravenous theophylline administration; however, only minor improvement was observed at the levels reached after relatively low oral doses. PMID- 4030163 TI - Pharmacokinetics of cimetidine in patients with liver disease. AB - Pharmacokinetics of cimetidine were studied after 200 mg i.v. doses in 7 patients with liver cirrhosis and in 10 healthy volunteers. Serial blood samples were obtained before and after drug administration over 12 hours. Cimetidine blood concentrations were determined by high pressure liquid chromatography (HPLC). The mean total body clearance in patients with cirrhosis (414.3 +/- 69.7 ml/min) was significantly less than that of subjects without liver dysfunction (501.1 +/- 37.9 ml/min) (p less than 0.01). However, the mean steady-state volume of distribution (1.34 +/- 0.41 l/kg vs 1.40 +/- 0.24 l/kg), volume of central compartment (0.51 +/- 0.11 l/kg vs. 0.45 +/- 0.05 l/kg), area volume of distribution (1.69 +/- 0.46 l/kg vs. 1.81 +/- 0.43 l/kg) and mean half-life (2.56 +/- 0.58 h vs. 2.68 +/- 0.43 h) did not demonstrate any significant changes. Renal clearance was significantly decreased from 389.5 +/- 41.9 ml/min in healthy subjects to 279.1 +/- 57.8 ml/min in cirrhotic patients (p less than 0.01). However, the mean extrarenal clearance was not changed in both groups. Modification of cimetidine dosage is therefore presumably not necessary in patients with compensated liver disease. PMID- 4030162 TI - Temporal variations of lorazepam pharmacokinetics. AB - Lorazepam pharmacokinetics were evaluated in eight healthy male and eight healthy female subjects after a single 3.5 mg oral dose. This randomized crossover study consisted of a morning dose (7:00 a.m.) or an evening dose (7:00 p.m.) separated by one week. While no consistent temporal changes in any parameter characterizing elimination of lorazepam were observed, absorption constant rate (Ka) and absorption half-life (t1/2a) were significantly modified by the hour of administration, the drug being more rapidly absorbed after the morning (t1/2a = 0.52 +/- 0.11) than after the morning trial (t1/2a = 1.18 +/- 0.26, p less than 0.05). Daily differences in pharmacokinetic parameters observed in this work suggest the need for taking in account the hour of administration during its pharmacokinetics determination. PMID- 4030164 TI - Theophylline: a diagnostic aid for evaluating chronic airways obstruction. AB - A study was carried out on the use of theophylline (240 mg by infusion) as a functional diagnostic test in patients showing severe chronic airways obstruction. The preliminary results suggested that the pharmacologic action of theophylline (a bronchodilating and vasoactive drug) helps discriminate the different types of anatomo-functional impairments present during a severe chronic bronchial obstruction. The changes in VA and VA/Qc induced by the drug were evaluated. The presence of a lesion mainly affecting the airways or the parenchyma of the lung might be identified by these changes. PMID- 4030165 TI - Variation in the relationship between serum and saliva lithium levels. AB - This study has been carried out to find out the reasons for the wide variations observed in the correlation between serum and saliva lithium levels. Serum/saliva lithium levels were monitored in 10 individuals on 6 occasions. The correlation coefficient (r) varied within individuals from 0.19 to 0.91 (p less than 0.025) whereas when all the individuals were considered simultaneously, it was 0.59 (p less than 0.005). It was concluded that prediction of serum lithium levels from salivary lithium levels would only be possible in those individuals showing good correlation. The variability in this correlation could be mainly due to inter individual variations in the particular sample of individuals studied. PMID- 4030166 TI - Clinical results obtained with a combination of an anti-inflammatory steroid, an antibacterial agent and an antifungal in dermatological outpatient practice. AB - Forty outpatients with skin diseases were treated with an extempore combination of three creams, the respective bases of which were beclomethasone dipropionate, sodium fusidate and ketoconazole. Positive results were obtained in 97.5% of the cases with good relief of symptoms and excellent local tolerance in all cases treated. PMID- 4030167 TI - Use of a combination of an anti-inflammatory corticosteroid, an antibacterial agent and an antifungal in the local post-operative treatment of cutaneo-mucosal diseases following cryosurgery. AB - Forty-two patients undergoing cryosurgery for skin diseases were treated by means of the simultaneous application of three creams, the respective bases of which were beclomethasone dipropionate, sodium fusidate and ketoconazole. The treatment produced excellent results, preventing bacterial and/or mycotic superinfections and relieving the edema and erythema caused by the operation in 97.6% of cases. Local tolerance was optimal in all cases; no adverse reactions of any kind being reported. PMID- 4030168 TI - Environmental considerations for substance use/misuse intervention. PMID- 4030169 TI - Adoption of the Uniform Alcoholism Act and the availability of alcoholism treatment programs: a state-by-state examination. AB - This research examines geographic differences in the availability of alcoholism treatment programs throughout the United States. Using a substantially complete national listing of alcoholism treatment programs, significant differences in treatment availability based upon state, division, and region were found. The variations in treatment availability were strongly related to the adoption of the Uniform Alcoholism Act, with the influence of the UAA being more pronounced in nonmetropolitan areas. Treatment availability was only weakly related to the extent of alcohol-related problems. It is suggested that the UAA may be adopted through the social mandates of metropolitan areas and that nonmetropolitan areas respond with increased treatment availability as a result of the legal mandate of the legislation. It is concluded that without the official redefinition of alcoholism as a condition requiring treatment, the establishment of an adequate treatment capability is severely impaired. PMID- 4030170 TI - Specific targeting of prevention programs in alcohol and drug dependence. PMID- 4030171 TI - Systematic toxicity testing of drugs. PMID- 4030173 TI - A personalized power scale for the prediction of alcoholism. AB - An objective test measure of personalized power was developed to test McClelland's hypothesis. Four existing personality questionnaires that have been considered to be relevant to personalized power were used. These scales were administered to 50 patients in a Veterans Administration alcoholism program and to 50 VA medical outpatients. Items which discriminated the groups at the p less than or equal to .20 level were included in a new scale, which was then cross validated on a new group of alcoholics and medical outpatients. The resulting 34 item scale was internally consistent (.83) and correctly classified 76% of the alcoholics and 94% of the medical outpatients. Overall, 86% were correctly classified as compared to an overall correct classification by the MacAndrew Scale of 67% on the same population. While the personalized power dimension seemed to add to the scale's predictive ability, the contribution of that dimension appears to be modest at best. PMID- 4030172 TI - Cross-cultural perspectives on teenage attitudes to alcohol. AB - Six hundred and seventy-seven indigenous Papua New Guinean, 315 Australian, and 166 American high school teenagers completed a series of measures on attitudes to alcohol. Papua New Guinean students differed most from other students in considering that money was wasted on alcohol and that preventive steps should be adopted to ban sales of take-away alcohol. In addition, Papua New Guinean males and females were more likely than other teenagers to feel that women should not drink alcoholic beverages. Within countries, males and females had fairly similar attitudes about alcohol and alcohol-related issues, and where differences occurred, males generally were less likely to highlight the costs of alcohol abuse. PMID- 4030174 TI - The role of tourism in alcohol-related highway fatalities. AB - Tourism and fatal single motor vehicle accidents, an index of alcohol-related motor accidents, are examined in a cross-sectional analysis of the 50 states of the Union and the District of Columbia. A multiple regression model is employed in which average mileage driven, percent of metropolitan residents, and number of licensed drivers are statistically controlled. Tourism is found to be positively associated with the single motor vehicle fatality rate. Further research and policy implications are discussed. PMID- 4030175 TI - Ethanol disposition in man: comparison of breathalyzer and two methods of gas liquid chromatography. AB - Blood and plasma ethanol concentrations were determined in 12 healthy male volunteers by gas-liquid chromatography (GLC) using direct injection (DI), headspace injection (HSI), and Breathalyzer (BR) analyses. Plasma concentrations as well as the blood:breath partition ratio of ethanol were higher by GLC-DI than by GLC-HSI. Regardless of analytical method used, the concentrations of ethanol in blood and rate of ethanol clearance from blood or plasma were unchanged. The partition ratio upon which the BR data are based appears adequate for individuals with normal pulmonary function. PMID- 4030176 TI - Temporal patterns of smoking topography in the natural environment. AB - Temporal patterns of smoking topography were studied in the natural environment. Six smokers smoked all cigarettes over a 10-day period using a small portable electronic recording device which allowed the measurement of a number of aspects of smoking topography. When the data were averaged in 2-hour blocks across the 10 day smoking period, all subjects except one showed differences in smoking topography as a function of time of day. There was considerable intersubject variability in the aspects of smoking topography which varied over the smoking day, and subjects also differed in the pattern of changes seen. PMID- 4030177 TI - Relaxation, noise-induced stress, and autonomic responsivity in male alcoholics and normal controls. AB - Skin conductance and heart rate activity were monitored in male alcoholics and normal controls before, during, and after the presentation of high-intensity (100 db) white noise. Analysis of nonstressful, pre- and postnoise periods indicated a relatively nonlabile pattern characterizing alcoholics as they exhibited lower skin conductance levels than normals and showed no changes in activity either within or between resting sessions. A similar pattern was observed in response to noise-induced stress as alcoholics exhibited significantly smaller changes in skin conductance and heart rate activity. PMID- 4030178 TI - Clinical experience with 781 cases of alcoholism evaluated and treated on an inpatient basis by various methods. AB - A retrospective study of 781 alcoholics detoxified at two treatment centers suggested that magnesium sulfate was significant in preventing seizures and that benzodiazepines were essential in minimizing other complications. Future investigations should determine the most effective mineral dosage levels for alcohol detoxification. PMID- 4030179 TI - Some principles of short-term group therapy. PMID- 4030180 TI - Guidelines for the practice of brief, dynamic group therapy. PMID- 4030181 TI - Utilizing group process in crisis-waiting-list groups. PMID- 4030182 TI - Time-limited inpatient group therapy: a developmental model. PMID- 4030183 TI - The problem-solving support group: structured group therapy with psychiatric inpatients. PMID- 4030184 TI - The value of inpatient group psychotherapy: patients' perceptions. PMID- 4030185 TI - Leadership in short-term group therapy: manipulation or facilitation? PMID- 4030186 TI - Justification of the 4-mmol/l lactate threshold. PMID- 4030187 TI - Hemorrheology of marathon running. AB - The hemorheological effects of severe exertion were evaluated in eight males and six females before and after a marathon. A highly significant fall in red cell filterability (RCF) was accompanied by a significant rise in plasma osmolality. This correlation was further studied by a series of in vitro experiments to establish a cause-effect relationship. As plasma osmolality increased, RCF progressively diminished. These observations demonstrate that plasma hyperosmolality is an important etiological factor in reducing RCF during strenuous exercise. PMID- 4030188 TI - Serum lipids in power athletes self-administering testosterone and anabolic steroids. AB - The purpose of the present investigation was to study the effects of testosterone and anabolic steroids on serum lipids in power athletes. Altogether 11 national top-level adult athletes completed the study. Five of them volunteered for the study group and the rest for controls. The follow-up consisted of 9 months of a strength training period. During the first 6 months, the subjects in the study group self-administered androgenic steroids on an average of 57 +/- 24.9 mg/day. The most interesting observation was the extremely low high-density lipoprotein (HDL) and HDL2 cholesterol concentrations of the androgen users. After 8 weeks of training, the study group had significantly (P less than 0.05) lower HDL cholesterol concentrations than the control group (0.53 +/- 0.11 and 1.14 +/- 0.19 mmol/l, respectively). This difference remained significant from 8 to 32 weeks of training. No systematic changes were observed in the control group. The HDL2 cholesterol concentration decreased by about 80% (P less than 0.01) and HDL3 cholesterol by about 55% (P less than 0.01) from the onset values in the study group. A substantial decrease in HDL cholesterol to total cholesterol and in HDL2 cholesterol to HDL3 cholesterol ratios were also noticed under the influence of exogenous androgens. The results of this study suggest that the sustained use of testosterone and anabolic steroids have a marked unfavorable effect on the pattern of HDL cholesterol in the serum of male power athletes. PMID- 4030189 TI - Thermoregulatory responses to weight training. AB - Thermoregulatory responses of eight healthy males (age 25.5 +/- 4.5 yrs) were studied during weight training comprising 3 sets of 15 repetitions of 9 exercises performed at a work cadence of 15 repetitions.min-1 with 1-min recovery intervals. The load for each exercise was increased from 50% of the 15-repetition maximum for the first set to 75% and 100% for the second and third sets, respectively. The thermoregulatory response was characterized by only moderate sweat rates (0.69 +/- 0.18 l.h-1) and rectal temperature rises (1.3 degree +/- 0.4 degree C, P less than 0.001), suggesting that dehydration and hyperthermia are unlikely to complicate weight training of the format used in this study. Despite a considerable lactic acidosis, small elevations in serum levels of aspartate aminotransferase and lactate dehydrogenase occurred, the core temperature rise being inadequate for significant cellular damage to ensue. Serum electrolyte levels measured immediately and 24 h post-exercise indicated that electrolyte supplementation is unlikely to be of benefit. Weight training induced a marked reduction of plasma volume (11.8% +/- 3.7%, P less than 0.001) in the presence of a minor water deficit (0.8% +/- 0.23%) and an O2 consumption of 32% +/- 8% of the predetermined treadmill exercise maximal O2 consumption. This finding suggests that exercise intensity as assessed by percentage maximal voluntary contraction rather than percentage maximal O2 consumption might determine the degree of hemoconcentration encountered during exercise. PMID- 4030190 TI - Exercises for knee flexors and extensors in uninjured soccer players: effects of two different programs. AB - The effects of two 4-week training programs on knee flexor and extensor strength were measured isokinetically (angular velocity 30 degrees, 180 degrees/s) and isometrically in division IV soccer players. Group A followed a team training program and group B an individual weight training program. Group C served as controls. Muscle strength was not increased by soccer training alone, but was increased by the individual training program, which resulted in significantly better knee extensor strength than did the team training program. PMID- 4030191 TI - Shoulder dislocation in skiing: choice of surgical method depending on the degree of humeral retrotorsion. AB - Shoulder dislocation is one of the typical upper extremity injuries in skiing, first following a violent accident but quite frequently recurring without new trauma. This article discusses the retrotorsional angle of the humerus as an etiological factor in the occurrence of an initial dislocation and as a triggering element for its recurrence. It focuses on the consequences to be drawn for the surgical treatment of recurrent shoulder dislocation. A technique for exact determination of the humeral angle of retrotorsion by X-ray is presented. In patients with recurrent anterior dislocations of the shoulder joint, the retrotorsional angle of the humerus is pathologically reduced as compared to the control group. The method of surgical therapy is determined by the individual deviance from the average value. PMID- 4030192 TI - Somatotype of athletes and their performance. PMID- 4030193 TI - Effects of pedal frequency on VO2 and work output at lactate threshold (LT), fixed blood lactate concentrations of 2 mM and 4 mM, and max in competitive cyclists. AB - To determine the effects of differing pedal frequencies on VO2 and work output values at the lactate threshold (LT), fixed blood lactate concentrations of 2 mM and 4 mM (2 mM, 4 mM), and at max, nine male competitive road racing cyclists (USCF category I or II) completed three VO2 max tests; on a Monark bicycle ergometer, at pedal frequencies of 60, 90, and 120 rpm. Each stage was 3 min in duration, starting at 0 kgm/min with subsequent stages increased by either 180 kgm/min (60 and 120 rpm) or 178 kgm/min (90 rpm). Blood samples were taken during the last 30 s of each stage. VO2 and work output at LT, 2 mM, and 4 mM were determined from individual blood lactate-work rate and VO2-work rate relationships. VO2 max and maximal work output were chosen as the peak values observed during the VO2 max tests. Results indicated that work output at LT, 2 mM, and 4 mM was affected by choice of pedal frequency (1278, 1140, 999 kgm/min at LT; 1533, 1450, 1182 kgm/min at 2 mM; 1780, 1703, 1487 kgm/min at 4 mM; for 60, 90, and 120 rpm, respectively, P less than 0.05). Max work output at 60 and 90 rpm was significantly greater (P less than 0.05) than at 120 rpm (2035, 2053, 1879 kgm/min for 60, 90, and 120 rpm, respectively).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4030194 TI - An unusual lesion in the knee of a breaststroke swimmer. AB - In a 21-year-old male breaststroke swimmer with characteristic symptoms in the medial aspect of the knee joint, synovial leakage suggesting medial capsular rupture caused by the whip kick was demonstrated arthrographically. PMID- 4030195 TI - Reduced hemoglobin concentration and red cell hemoglobinization in Italian marathon and ultramarathon runners. AB - Red blood cell indices, serum iron, and serum ferritin concentration were determined in 45 marathon runners, 56 ultramarathon runners, and 32 healthy sedentary controls. A significant reduction of hemoglobin concentration, hematocrit, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, mean corpuscular volume, serum iron, and serum ferritin were found in marathon runners compared to control subjects. The same variables were also reduced, but to a lesser extent, in the less trained ultramarathon runners. The decreased hemoglobin concentration demonstrated in the runners examined is related to both a reduced mean corpuscular hemoglobin concentration and a reduced hematocrit and may depend on a reduction of the body iron stores. PMID- 4030196 TI - Stabilometry recordings in functional and mechanical instability of the ankle joint. AB - Functional instability, i.e. recurrent sprains or a feeling of giving way in the joint, is common after ankle sprain. Using stabilometry, an objective and quantitative method for studying postural control, we earlier showed that soccer players with pathological stabilometric results are at risk for ankle joint injury. In the present study we found that the ability to maintain postural equilibrium as demonstrated by stabilometry was reduced among players with functional instability, but was not affected by mechanical instability. The results indicate that coordination and postural control are important for functional instability of the ankle. PMID- 4030197 TI - Therapeutic doses of phenylpropanolamine increase supine systolic blood pressure. AB - The anorectic agent phenylpropanolamine (PPA) has a low therapeutic index and can cause severe hypertension at doses as low as 85 mg. To determine the effects of a therapeutic dose on blood pressure, PPA 37.5 mg (as a commercially available immediate release formulation) or placebo was administered orally to ten normotensive subjects using a randomized double-blinded crossover design. The mean increase in supine systolic blood pressure (BP) was greater after PPA (18.5 +/- 10.7 mmHg) than after placebo (5.1 +/- 5.4 mmHg, P = 0.005). Increases in systolic BP after PPA ranged from 8 to 43 mmHg. The BP increase due to PPA was postural, and there was no change in sitting or standing BP. Doses of PPA available in over-the-counter formulations can increase supine systolic BP. Recent use of products containing PPA should be considered when evaluating patients with hypertension. PMID- 4030198 TI - Suppression of norepinephrine-induced thermogenesis in human obesity by diet and weight loss. AB - The response of metabolic rate to norepinephrine infusion was studied in seven obese subjects before and after large amounts of weight loss. Resting metabolic rate fell from a mean of 2254 kcal (9.4 MJ) to 1682 kcal (7.0 MJ) per 24 h. The thermic response to norepinephrine infusion was reduced by 50 percent from 7527 (31.5 MJ) to 3369 (14.0 MJ) kcal/24 h/T0-45 following weight loss and on continued diet. This adaptation to weight loss could contribute to the diminished rate of weight loss that occurs with continued dieting. Previous contradictory findings of normal and reduced norepinephrine-induced thermogenesis in human obesity could result from subjects being studied under different dietary conditions. PMID- 4030199 TI - Quetelet's index (W/H2) as a measure of fatness. AB - A weight-height index of adiposity should indicate the relative fatness of subjects of differing height unless obesity is itself correlated with height. The average body fat among adult women attending a hospital outpatient clinic for obesity was 40.5 percent of body weight. The height of an unselected series of 286 of these outpatients was found to be similar to that of the general population of women of similar age, which indicates that obesity in adult women is not significantly related to height. Body composition was measured by body density, body water and body potassium in a series of 104 female and 24 male subjects aged 14-60 years. In both sexes density, water and potassium gave progressively higher estimates of body fat (kg), and there was a significant difference between the values by different methods. The average of the estimates by these three methods was taken to be the 'true' value for each individual (F kg). Regression of F/H2 on W/H2 (Quetelet's index) gave a correlation coefficient of 0.955 for women and 0.943 for men. The deviation of the body fat estimated from Quetelet's formula from the 'true' value was not much greater than that when density, water or potassium were used as a basis for estimating body fat. It is concluded that Quetelet's formula is both a convenient and reliable indicator of obesity. PMID- 4030200 TI - External responsiveness to food and non-food cues among obese and non-obese children. AB - External responsiveness to food and non-food cues was studied among 112 obese and 134 non-obese children ranging in age from 42 to 156 months. Subjects viewed five food and five non-food items and stated a preference between an immediate smaller and a delayed larger choice. Young (ages 3-5 years) children's abilities to delay gratification were significantly lower than were those of school children, a finding consistent with research on delay of gratification. Obese subjects at both ages had lower delay scores for immediate gratification on food items than did non-obese subjects. The delay scores of obese and non-obese subjects on non food items were not significantly different from each other. Results were discussed in terms of the ontogeny of externality. PMID- 4030201 TI - Localization and associated histopathology of asexually proliferative Mesocestoides corti tetrathyridia (Cestoda) infecting mouse mammary glands. PMID- 4030202 TI - Characterization of Trypanosoma (Duttonella) vivax by isoenzyme analysis. PMID- 4030203 TI - Immunization and immunosuppression in mice reared for high or low immune responsiveness against Nematospiroides dubius. PMID- 4030204 TI - Spermatogenesis in a nematode Nippostrongylus brasiliensis. PMID- 4030205 TI - The effect of dosage regimen on the efficacy of cambendazole against Trichinella spiralis. PMID- 4030206 TI - The site distribution of adult strongyle parasites in the large intestines of horses in tropical Australia. PMID- 4030207 TI - Immune responses to Trichinella pseudospiralis and Trichinella spiralis in mice. PMID- 4030208 TI - Schistosoma mansoni: parasitology and immunology of baboons vaccinated with irradiated cryopreserved schistosomula. PMID- 4030209 TI - Influence of primary infection on the population dynamics of Nematospiroides dubius after challenge infections in mice. PMID- 4030210 TI - Experimental observations on the transmission of Schistosoma margrebowiei miracidia. PMID- 4030211 TI - Morphological studies on the early development of Taenia taeniaeformis larvae in susceptible mice. PMID- 4030212 TI - Damage and early destruction of Taenia taeniaeformis larvae in resistant hosts, and anomalous development in susceptible hosts: a light microscopic and ultrastructural study. PMID- 4030213 TI - An ultrastructural study on the encapsulation of microfilariae of Brugia pahangi in the haemocoel of Anopheles quadrimaculatus. PMID- 4030214 TI - Phosphatidylethanolamine synthesis in adult Dirofilaria immitis females. PMID- 4030215 TI - Synthesis of protected peptides with the sequence 8-13-1-3 and 4-13-1-3 of mycobacillin and their analogs. AB - We have synthesized both a protected nonapeptide of the mycobacillin 8-13-1-3 amino acid sequence and a protected tridecapeptide of the 4-13-1-3 sequence, which are a fragment and a open chain analog of this antibiotic, respectively. Some of their analogs with a reversed configuration of the amino acids at fixed positions have also been synthesized. The nonapeptides were obtained by coupling partially protected mycobacillin fragments with the sequence 8-10 and 11-13-1-3 while the tridecapeptides were synthesized by coupling partially protected fragments 4-7 and 8-13-1-3. Configuration analogs of these fragments were also used. The coupling methods applied were DCCI/HONSu or DCCI/HOBt. The purification of the synthesized peptides was achieved by means of recrystallization or column chromatography on silica gel. They were characterized mainly by m.p., degree of optical rotation, elemental and amino acid analysis. PMID- 4030216 TI - Solution conformations of valinomycin-divalent cation complexes. AB - The solution conformations of complexes of valinomycin with magnesium and strontium were investigated by circular dichroism, nuclear magnetic resonance and infrared techniques. The results were compared with our earlier results on lithium, calcium, manganese and barium complexes. All these cations, except lithium, form 2:1 ion sandwich and 1:1 carrier-cation complexes with valinomycin. The 1:1 complex has a conformation different from that of the valinomycin potassium complex. Lithium forms only the 1:1 complex. Strontium and barium form a large number of 1:2 complexes with open conformations rapidly interconverting in solution in addition to the above 2:1 and 1:1 complexes. These observations are rationalized taking into account the ionic radii and coordination numbers of the cations and the conformational restraints of valinomycin molecules. It is suggested that cations with co-ordination numbers of about six (magnesium and calcium) form the 2:1 and 1:1 complexes whereas those with higher co-ordination numbers (strontium and barium) form 1:2 complexes also. PMID- 4030217 TI - Formation of water-soluble complex between the 1-34 fragment of parathyroid hormone and dimyristoylphosphatidylcholine. AB - Two biologically active, 34 amino acid fragments of parathyroid hormone interact with dimyristoylphosphatidylcholine to form lipoprotein particles. In the lipid bound form these parathyroid hormone peptides exhibit an increased amount of folded secondary structure and the tryptophan residue of [Nle8, Nle18, Tyr34] b PTH (1-34) amide appears to become buried in a more hydrophobic environment. The lipoprotein particle which is formed has dimensions of approximately 65 X 7 nm but aggregates to larger structures with increasing temperature. Above the phase transition of the phospholipid the peptides no longer affect the morphology of the lipid and the spectral properties of the peptide are not perturbed by the lipid. This is similar to the behavior of glucagon with dimyristoylphatidylcholine. The results indicate that several nonhomologous peptide hormones have common features which allow them to fold into an amphipathic helix and solubilize phospholipid. PMID- 4030218 TI - Effect of alkylation with different sized substituents on the conformation of ovomucoid, lysozyme and ovotransferrin. AB - Conformational changes induced in ovomucoid, lysozyme and ovotransferrin on reductive addition of different sized substituents have been studied employing differential scanning calorimetry (DSC) and circular dichroic spectroscopy (CD). The thermograms obtained by DSC revealed that extensive introduction of methyl, isopropyl, cyclopentyl, cyclohexyl, benzyl or n-butyl groups has a detrimental effect on thermal stability (enthalpy of denaturation); the effect generally increases with the size of the substituent. Circular dichroic spectra were affected only to a very limited extent by the modifications, near-u.v. spectra remaining much the same while far-u.v. spectra displayed minor changes. The general conclusion drawn is that the modifications had only limited effects on the conformation of the proteins while, nonetheless, perturbing (or breaking) long-range intramolecular interactions so as to destabilize the structure. Derivatization of lysozyme and ovotransferrin with some of the larger groups has been reported to result in spontaneous precipitation of the proteins [Fretheim, K., Iwai, S. & Feeney, R.E. (1979) Int. J. Peptide Protein Res. 14, 451-456]. The present investigation indicates that precipitation was caused by (partial) denaturation (and ensuing aggregation) as a consequence of modification. PMID- 4030219 TI - Round table on treatment of macular degeneration, possibilities of argon and krypton lasers. PMID- 4030220 TI - Clinical usefulness of cellulose acetate electrophoresis as a screening of proteinuria in childhood. AB - Urine samples from 110 patients with different proteinuric diseases in childhood were analysed by Cellulose Acetate Electrophoresis (CAE) and several samples were also analysed by Sodium Dodecyl Sulphate Polyacrylamide Gel Electrophoresis (SDS PAGE). CAE allowed the classification of proteinurias into 4 patterns; Tubular, Glomerular I, Glomerular II and Glomerular III, by albumin/globulin ratio, value of % gamma globulin fraction (% gamma) and alpha 1/alpha 2 globulin ratio. Proteinurias of the Tubular pattern included various diseases with tubular proteinuria, while proteinurias of the Glomerular I, II and III patterns included mainly postural proteinuria, proteinuria of nephrotic syndrome and proteinuria of various nephropathies, respectively. SDS-PAGE confirmed the tubular and the glomerular origins of the proteins. In the present study we described the clinical usefulness of CAE in the screening of proteinuric children for the following reasons. This method could be performed easily and immediately. This is one of the necessities for mass screening of proteinuric children. CAE can be helpful as one of indications of renal biopsy, since patients with the Glomerular III pattern often showed glomerular alterations and should be diagnosed histologically. Good correlation between % gamma and clinical data was found in follow-up study, so CAE is also helpful in understanding the disease course. Thus. CAE is recommended as a routine screening method of proteinuria as well as SDS-PAGE. PMID- 4030221 TI - Incorporation of 35sulfate into the glomerular basement membrane in puromycin aminonucleoside nephrosis. AB - The in vitro incorporation of 35sulfate into the glomerular basement membrane (GBM) of rats with puromycin aminonucleoside was compared with that of normal rats. 35Sulfate incorporation into the GBM of glomeruli from nephrotic rats did not differ significantly from that observed in normal rats. These data suggest that 35sulfate anionic charges in the GBM play no important role in the pathogenesis of the proteinuria in this experimental model. PMID- 4030222 TI - Computerized tomography of the brain in children with chronic renal failure. AB - We performed computerized tomography (CT) of the brain in 22 patients, 2 to 18 years of age, with stable chronic renal failure (n = 6), on dialysis (n = 14) and after renal transplantation (n = 2). None suffered from a systemic disease known to affect the central nervous system (CNS) and none had overt CNS dysfunction at the time of the CT examination. The most striking pathological finding was brain atrophy, which was present in 13 patients (59%). In two patients cortical infarcts were present and one patient was found to have a hypodense area in the basal ganglia. The brain atrophy could not be related to the type of basic renal disease, the age of the patient, corticosteroid dosage, the duration of the renal failure or the presence of hypertension However, the mode of treatment, i.c. hemodialysis, seemed to be a risk factor. We assume that metabolic derangements and/or the accumulation of toxic substances due to the uremic state may be responsible for the brain atrophy in young patients with CRF. Recurrent osmotic changes of the brain during hemodialysis may aggravate the process of brain atrophy. PMID- 4030223 TI - The dental status of children with chronic renal failure. AB - We evaluated the dental status of thirty children with chronic renal failure (CRF): 15 managed conservatively, 9 on dialysis replacement therapy and 6 after kidney transplant. Dental age was delayed, but to a lesser extent than bone age; this delay was most marked where CRF occurred before 7 years of age. Eruption age was only minimally delayed. Eighteen patients (60%) showed enamel defects, mainly hypoplasia, the location of which was related to the age at which major metabolic changes of uremia appeared. In 9 children (30%) there was intrinsic discoloration of the teeth--this was also related to the severity and duration of CRF. Compared to normal Israeli children our patients showed poor oral hygiene and gingival condition, but a significantly lower prevalence of caries. Seven patients (23%) showed mild radiologic changes in the jawbones (mainly loss of lamina dura), the severity of which was related to the severity and duration of CRF. None of the above findings could be related to specific metabolic disturbances. PMID- 4030224 TI - Thalassemia B with distal renal tubular acidosis: a previously undescribed association. AB - An infant with beta thalassemia major and distal renal tubular acidosis is described. Screening of forty patients with beta thalassemia major revealed no evidence of renal tubular acidosis. Although the possibility of coincidence cannot be completely excluded, we suggest that beta thalassemia major should be added to the list of conditions associated with distal renal tubular acidosis. PMID- 4030226 TI - Abstracts. 1st National Congress of the Italian Society of Pediatric Nephrology. May 14-15, 1985, Naples, Italy. PMID- 4030225 TI - Focal segmental glomerulosclerosis and Charcot-Marie-Tooth disease. PMID- 4030228 TI - Use of community services by the elderly 3 and 12 months after discharge from hospital. AB - The evidence that admission to hospital affects the use of community services by the elderly is conflicting and incomplete. 2711 over 65's admitted to acute hospitals in Wales were studied, using a postal questionnaire, comparing services used before and after admission. Usage of services did increase although at 1 year had dropped back. The patterns of usage are described, relating them to the types of patient. Entering hospital did not lead to losing contact with community services previously used. PMID- 4030227 TI - Divergent membrane maturation in rat kidney: exposure by dietary taurine manipulation. AB - Taurinuria is characteristic of the immature rat. The excessive taurine loss could be the result of brush border or basal lateral membrane immaturity. The beta-amino acid, taurine, and D-glucose were examined using isolated brush border membrane vesicles (BBMV), slices and tubules prepared from 28-day-old rats. In BBMV, taurine accumulation was inversely proportional to osmolarity, indicating uptake rather than binding, and taurine accumulation was Na+-dependent. BBMV from 28-day rats did not accumulate D-glucose to the same degree as in adult BBMV, and the initial rate of uptake was slower. Taurine uptake had a similar Km and Vmax in BBMV from immature rats. Despite similarities in the kinetics of taurine uptake, higher urinary taurine concentrations are found in younger rats. The efflux of taurine from slices and tubules was much slower than in adults and probably accounts for the taurinuria of young animals. A diet low in methionine and taurine (LTD) given for seven days resulted in a lower excretion and fractional excretion of taurine than in animals fed a normal sulfur amino acid diet (NTD). A high-taurine diet (HTD) causes excessive taurinuria. These patterns of excretion are reflected at the brush border membrane surface with greater uptake after the LTD and reduced uptake after the HTD. A kinetic analysis of adult and 28-day-old animal BBMV reveals that the Vmax of accumulation is altered by diet, whereas the Km remains unchanged. The Vmax is higher in BBMV from LTD animals and lower in BBMV from HTD animals.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4030229 TI - Application of the Classification of Disabilities to children from 12 to under 16 years of age. AB - In 1984 we investigated 480 physically and/or mentally impaired children, in the age group 12-16 years, including 208 mentally handicapped children. They were classified with the help of the International Classifications of Disability (WHO). We analysed the frequency distributions of every item of the Classification of Disability. As a result of this analysis we suggest a reduction of the number of categories. PMID- 4030230 TI - What would physiotherapists in geriatric medicine do if they had more staff? AB - Forty-one per cent of UK physiotherapy departments responding to a questionnaire felt that they had sufficient staff, and these had more physiotherapists per elderly population than those who felt that they had insufficient staff. At present 77% of therapist time is spent in direct patient contact. There were areas where it appeared that an excessive amount of time was being spent in administration etc. Therapists felt that, with more staff, there would be an increase in the intensity of treatment, group therapy, work with long-stay patients and more pre-discharge home visits. Very few units would carry out research even if more time was available. PMID- 4030231 TI - Hearing disorders in childhood, some procedures for detection, identification and diagnostic evaluation. AB - Hearing disability in childhood is a sign/symptom which should be detected, in order to avoid developmental disorders in language, speech, psychological and mental behavior. For proper treatment the hearing thresholds should be identified and the site of lesion evaluated in order to obtain a classification of the hearing loss. The causative factor(s) of the hearing disorder should be evaluated by means of an interdisciplinary cooperation. This review summarizes the results obtained in a series of investigations dealing with some procedures for detection, identification and nosological classification of hearing impairment in childhood. Based on these investigations a model for an examination program is proposed. This model requires interdisciplinary cooperation, preferably established at assessment centers. Prospective studies performed at these centers may offer precise data on the epidemiology of hearing disorders. Consequently preventive measures may be applied in order to reduce the number of children suffering from the symptom of hearing loss. PMID- 4030232 TI - Noise-induced hearing loss and portable radios with headphones. AB - Portable radio/cassette players with headphones have gained increasing popularity in recent years. Volume settings are often increased to override environmental noise, perhaps placing the listener at risk for noise-induced hearing loss (NIHL). A total of 190 public college students in NYC were studied via a self administered questionnaire regarding the volume setting used and weekly exposure in hours to these units. Three popular models were tested using a Bruel and Kjaer sound level meter, octave band filter and artificial ear. Sound levels were measured at various frequencies (250-8000 Hz) and an overall measurement obtained using the "A"-weighted scale. Based on OSHA criteria for permissible noise dose (i.e. intensity X duration) in the work place, auditory risk criteria were developed. Of all students who used such radios 31.4% equalled or exceeded the maximum allowable dose permitted by these criteria (41.2% of the males and 29.2% of females). This sex-related difference in risk, while not statistically significant, warrants further investigation. Of the total 'at risk' group 50% exceeded the risk criteria by more than 100%. These results suggest that portable radios with headphones may be capable of causing permanent hearing loss in a large proportion of radio users. PMID- 4030234 TI - Recurrent suppurative thyroiditis due to fourth branchial pouch sinus. AB - Acute suppurative thyroiditis is a rare disease in childhood. The etiology of this condition is not always obvious. The description of a pharyngeal pouch fistula extending from the pyriform sinus to the thyroid gland or perithyroid area, high-lighted the etiopathogenesis of some of the thyroiditis cases. Presented here are the clinical, radiological and pathological aspects of an internal pharyngeal fistula manifesting with recurrent suppurative thyroiditis, until it was completely removed. The clinical features of caudal branchial pouch remnants and their role in the development of acute suppurative thyroiditis is reviewed. PMID- 4030233 TI - Maturation of auditory brainstem potentials in neonates and infants. AB - Auditory brainstem evoked potentials (ABP) were recorded in 59 healthy neonates and infants whose age ranged from 3 days to 18 months (6 age groups). Latencies of individual waves and the interpeak latencies (IPL) of I-III, III-V and I-V were analysed. A different maturational pattern was observed in the pontomedullary and the pontomesencephalic segments of the brainstem. Latencies of all waves except wave I were longer in male than in female babies. Establishment of normative data related to the technical variables employed by the individual team is a sine qua non prerequisite for adequate neurological evaluation of ABP. PMID- 4030235 TI - Auditory brainstem response (ABR) to tone pips in hearing-impaired children. AB - The correspondence between ABR thresholds to tone pips and behavioral thresholds at 500, 1000 and 2000 Hz was studied in 13 normal and 55 hearing-impaired children, including 42 sensori-neural losses and 13 conductive losses. The children's ages ranged from 1 year 3 months to 8 years. Tone pips were provided with 2-cycle rise-fall times and 2-cycle plateaus. The correlations between the two measures were highly significant at 3 frequencies both in sensori-neural losses and conductive losses. In the subjects with sensori-neural losses, the ABR thresholds tended to be lower than the behavioral thresholds. Mean threshold differences between the ABR and behavioral audiometry at each frequency in sensori-neural losses were 1.6, 0.26 and 5.8 dB, respectively. On the other hand, in the subjects with conductive losses, the ABR thresholds were higher than the behavioral ones by 9.6, 7.8 and 7.5 dB at respective frequencies. Therefore, the hearing acuity in young children with sensori-neural losses can be predicted with accuracy from the ABR thresholds to tone-pips at 500, 1000 and 2000 Hz. PMID- 4030236 TI - Normal values of mucociliary transport time in young subjects. AB - The authors studied the behaviour of nasal mucociliary transport (MCT) in 54 (33 female/21 male) normal children aged between 3 and 12 years, in orthostatic and clinostatic positions. The nasal MCT time was recorded with the stained tracer method; vegetal coal powder was used since it fulfills the required characteristics: it is neither toxic, nor soluble and can be easily detected. The examinations were carried out at the same time of day on two consecutive days under the same conditions of temperature and relative humidity. The statistical analysis of the results indicated an average nasal MCT time of 9.96 +/- 2.61 min in the orthostatic (upright) position and of 9.98 +/- 2.31 min in the clinostatic (lying) position: these values should be considered normal. No statistically significant difference was noted attributable to sex or posture. PMID- 4030237 TI - Treatment of infantile subglottic hemangioma. A report of 49 cases. AB - Forty-nine laryngeal subglottic hemangiomas were observed in infants over a 9 year period. The diagnosis was always confirmed by direct laryngoscopy. The outcome of 42 of these hemangiomas was studied. A total of 26 infants recovered completely after medical treatment and 16 were intubated; only 4 underwent a tracheostomy. Short-term steroid therapy was sufficient in 7 infants, but long term administration of corticosteroids was necessary in 14 cases. In 10 of the 16 intubated cases it was possible to withdraw corticosteroids permanently. Of the 6 remaining cases, 32P contact radiation therapy was tried in 2 cases of which one was successful, CO2 laser in 2 cases without success, tracheostomy alone in one case and one child died 2 months after extubation, without dyspnea. This series leads us to recommend corticosteroids as a first therapeutic step and short-term nasotracheal intubation if unsuccessful. PMID- 4030238 TI - Chronic pediatric tracheotomy: assessment and implications for habilitation of voice, speech and language in young children. AB - The effect of chronic tracheotomy on the acquisition of voice, speech, and language skills was studied. Children with chronological ages of 16 months to 41 months were evaluated for Receptive Communication Age (RCA) and Expressive Communication Age (ECA). Results indicate a consistent deviation of (on the average) 4.8 months delay in RCA and 9 months delay in ECA. An habilitation program for early intervention in voice, speech and language stimulation is described, with follow-up data on 3 children. A progression from non-meaningful, non-vocal communication to more meaningful and functional communication is noted. The evidence indicates that, without therapeutic intervention, children with tracheotomies are at risk for delays in receptive and expressive language development, as well as deficits in oral/vocal speech and voice production. PMID- 4030239 TI - Nocturnal enuresis in children with upper airway obstruction. AB - This article reviews 35 children between the ages of 3 1/2 and 11 years who have had symptoms of upper airway obstruction and enuresis. Twenty-eight patients had primary enuresis, and 7 had secondary enuresis. Removal of upper airway obstruction by surgical intervention led to a significant decrease or complete cure of nocturnal enuresis in 26 patients. Four children were studied with polysomnographic tracings in relationship to their enuresis. PMID- 4030240 TI - Obstructive hypertrophic adenoids and tonsils as a cause of infantile failure to thrive: reversed by tonsillectomy and adenoidectomy. AB - Isolated failure to thrive in an infant caused by chronic hypoventilation due to hypertrophic adenoids and tonsils, has not been previously described. A 9 month old infant presented with weight loss and mild clinical respiratory signs. Hypoxemia and CO2 retention, however, were documented by transcutaneous gas measurement, and ENT examination revealed enlarged tonsils and adenoids. Adenoidectomy and tonsillectomy at 9 1/2 months of age completely reversed the patient's hypoventilation and growth pattern. While the exact mechanism of failure to thrive secondary to upper airway obstruction in infancy is not clear, we conclude that routine ENT evaluation should be a regular part of the workup of infants under one year who suffer from failure to thrive. PMID- 4030241 TI - Postoperative macroglossia causing airway obstruction. AB - Macroglossia can cause a wide spectrum of problems in the pediatric population. Airway obstruction is the most severe of the sequelae and must be handled promptly. Typically, congenital macroglossia does not present with sudden airway obstruction, however, traumatic or postoperative macroglossia can. Iatrogenic postoperative macroglossia is presented and mechanisms of injury discussed. Preventative and therapeutic measures are outlined. PMID- 4030242 TI - Facial paralysis due to primary tuberculosis of the parotid gland. AB - An 11-year-old girl presented with parotid mass and facial paralysis due to primary TB of the parotis gland. The diagnosis was made only postoperatively, by histology, and microscopic examination for acid and alcohol fast bacilli. PMID- 4030243 TI - A model of peripheral microvascular injury: irreversible caudal necrosis induced in carrageenan-inflamed rats treated with anti-inflammatory drugs and mild chilling: a pluricausal thrombo-haemorrhagic phenomenon. AB - A florid tail injury was observed in carrageenan-inflamed rats previously treated with acidic non-steroidal anti-inflammatory (NSAI) drugs to suppress paw inflammation and then exposed to mild chilling (7-10 degrees C for 10-16 h). All three treatments, i.e. NSAI drug + carrageenan paw oedema + mild chilling treatment, were required for the development of this condition. Histological observations suggest that the tissue necrosis was initiated by a primary disturbance of the peripheral vasculature. The possible involvement of suppressed prostaglandin (PG) production in the aetiology of this condition is indicated by the fact that it was totally reversed by prior treatment with PGE2. This appears to be a classical pluricausal thrombohaemorrhagic phenomenon (of Selye), with cold-stress being the sensitizer and carrageenan and NSAI drugs being the challenger. The possibilities are considered of employing this tail injury model as a convenient method of developing drugs to control microvascular disturbances in man. PMID- 4030244 TI - Interaction between glioma cells and normal brain tissue in organ culture studied by scanning electron microscopy. AB - Scanning electron microscopy was employed to investigate cocultures between normal rat brain fragments and spheroids consisting of rat glioma cells. Lamellipodia were seen to arise from tumor cells at the border between the two structures and touch the surface of the fragment. Cytoplasmic extensions from malignant cells appeared to penetrate into the brain fragment. Leading lamellae were extended from the tumor cells as they migrated along the normal surface and gradually covered the fragment. Tumor cells formed broad foot-plates against the normal surface. No alterations of the brain fragment were observed ahead of the tumor cells. Thus there were specific changes of the surface microarchitecture of the malignant cells, but not of the normal brain tissue. PMID- 4030245 TI - Adhesion and spreading characterization of a rat tumor cell system exhibiting different metastatic behavior. AB - The rat tumor cell system BSp73AS/BSp73ASML was investigated for its structural aspects. The non-metastasizing line BSp73AS has less nuclear atypism than the metastasizing line BSp73ASML. Microvilli are scanty and variable in length and structure; in BSp73ASML they cover the cells densely, are short and homogeneous in size. In vitro adhesion and spreading tests show structurally flexible BSp73AS cells which flatten completely onto substrata. BSp73ASML cells remain spherical and develop only small attachment areas. In vitro aggregation of the BSp73AS cells leads to round, tightly packed aggregates, their outer cell layer is epitheloid BSp73ASML cells form clusters of mostly ball-shaped cells. Surprisingly, as judged from EM images, the intercellular junctions in BSp73ASML cell clusters are qualitatively the same as in BSp73AS cell aggregates. However, the extent of apposition between cells in BSp73AS aggregates is much higher than between cells in the BSp73ASML clusters. BSp73ASML cells lack the ability to vary their shape. This is the prominent difference revealed by these tests between the two cell lines. Hence, this fact could play an important role in their different metastatic behavior in vivo. We speculate that the ability to vary the cell shape is necessary for expansive growth in the host environment but not for the metastatic spread. PMID- 4030246 TI - Repression of lymphatic metastasis by a second implant of the same tumor. AB - Previous work in the rat D-12 fibrosarcoma model has shown that the incidence of macroscopic metastasis, located primarily in regional lymph nodes, is markedly increased after surgical removal of a primary subcutaneous tumor implant, in all probability by facilitating the outgrowth of already established micrometastases. The present work shows that a second implant of live D-12 tumor cells into a remote site effectively represses the outgrowth of macroscopic metastases. For the manifestation of the repressive effect, both the time interval elapsing between surgery and reimplantation of tumor cells and the size of the inoculum appear critical. Implantation of heavily irradiated D-12 cells or the prolonged delivery of ascites fluid by osmotic mini-pumps had no such repressive effect on metastatic tumor growth. Corynebacterium parvum administered into the tumor bearing limb a few days before its amputation, but not into a remote subcutaneous site, suppressed the outgrowth of macroscopic metastases. The occurrence and efficient operation of concomitant tumor resistance in the D-12 tumor model, in which metastasis is primarily via lymphatics and resistance appears to involve a substantial portion nonspecific reactivity, is further evidence for a basic role of tumor/tumor interrelations in determining the final outcome of the host/tumor interaction. PMID- 4030247 TI - Enhancement of the incidence of metastasis in tumor-resected mice. Influence of soluble tumor extract and splenectomy. AB - The M3 mammary tumor was transplantable in syngeneic BALB/c mice, and metastasized spontaneously into the lungs. When primary tumors were resected in early stages of evolution (10 days), the number of mice with lung metastasis decreased. When specific soluble tumor extracts, tumor cell culture supernatant or formalinized tumor cells were inoculated 2 and 4 days after surgery, an enhancement of lung metastasis was observed. When splenectomy was performed at the time of tumor resection, this enhancement was abrogated. These results suggest that tumor plasma cell membranes or the products released by them play an important role in dormant metastases growth, but only in the presence of the spleen, suggesting its involvement in the mechanism of the metastatic process. PMID- 4030248 TI - Fluorescent dyes demonstrate the uniform expansion of the growing rabbit cornea. AB - Thiocyanate and triazinyl chloride derivatives of fluorescent dyes have been employed for the covalent labeling of components of the connective tissue of the rabbit cornea. Collagen is the major macromolecular component that becomes dyed. Some of the stromal components that are labeled by these reagents in the first two weeks of life persist over many months, but are progressively dispersed over a greater area consistent with a uniform expansion of the tissue with growth without complete turnover. These dyes may find useful application in the morphologic study of other persistent connective tissue components during development and wound healing. PMID- 4030249 TI - Keratocyte survival following a controlled-rate freeze. AB - One of the major drawbacks of cryorefractive surgery is the delay in the postoperative recovery of corneal clarity. The authors have hypothesized that this delay is due to the death of graft keratocytes caused by the freezing process, and the need for subsequent repopulation by host keratocytes to restore corneal clarity. By using a slow, controlled-rate freeze on a modified Barraquer cryolathe, the authors are able to maintain keratocyte viability in the graft corneal tissue, as assessed by standard histologic methods and by collagenase digestion. Maintenance of keratocyte viability results in the rapid return of corneal clarity following lamellar keratoplasty in the rabbit, with few of the histopathologic changes seen following standard rapid freezing of corneal tissue. PMID- 4030250 TI - Ocular inflammation in autoimmune MRL/Mp mice. AB - Congenic mice of the MRL/Mp strain spontaneously develop an autoimmune connective tissue disease that shares immunologic and histopathologic features with the human disorders systemic lupus erythematosus, rheumatoid arthritis, and systemic vasculitis. The autoimmune disorder in these mice is markedly accelerated by the recessive gene lpr. Older MRL/Mp-lpr/lpr mice develop significant inflammatory ocular disease, including choroiditis, scleritis, and orbital vasculitis. Animals of both the MRL/Mp-+/+ and MRL/Mp-lpr/lpr substrains develop lacrimal gland inflammatory infiltrates. The MRL/Mp mouse provides a potential model for ocular inflammatory disease and for Sjogren's syndrome. PMID- 4030251 TI - Dependence on antibody for induction of chemiluminescence in polymorphonuclear leukocytes by herpes simplex virus. AB - The induction of luminol-dependent chemiluminescence in rabbit polymorphonuclear leukocytes (PMN) by a stromal keratitis causing strain (RE) of herpes simplex virus type 1 (HSV-1) was examined. Virus alone and virus infected rabbit corneal cells were unable to stimulate chemiluminescence. However, when the virus or virus infected cells were incubated in the presence of HSV-1 specific immune serum or purified IgG, a gradual chemiluminescent response was observed. Virus and virus infected cells incubated with normal rabbit serum or IgG produced little or no activity. No impairment of chemiluminescent response was observed in experiments in which rabbit PMN were exposed to HSV prior to the addition of opsonized zymosan or HSV-antibody complexes. Results suggest PMN exert antiviral activity in the presence of specific antibody and may be important factors in the inflammatory process resulting from ocular HSV infection. PMID- 4030252 TI - In vitro enhancement of anterior chamber GVH reactions. AB - The injection of sensitized allogeneic lymphocytes into the anterior chamber of the rabbit eye results in a local graft-verus-host reaction, with focal destruction of the corneal endothelium. This experimental model permits in vitro manipulation of effector cells, and the study of the mechanisms involved in corneal graft rejection. The authors now show that the in vitro activation of sensitized lymphocytes is a one-way mixed lymphocyte reaction yields "supersensitized" effector cells which are quantitatively enriched and qualitatively altered to yield more severe and more rapid endothelial target cell destruction. PMID- 4030253 TI - The complement system and host defense against Pseudomonas endophthalmitis. AB - The authors examined the role of the complement system in host defense against Pseudomonas aeruginosa endophthalmitis. Guinea pigs received intravitreal injections of P. aeruginosa, and comparisons were made between bacterial counts from the vitreous of control guinea pigs and experimental guinea pigs that underwent systemic decomplementation with cobra venom factor. In group 1 (intravitreal injection of 42 organisms), bacterial counts were significantly higher in the vitreous of decomplemented guinea pigs versus control guinea pigs at days 1, 2, and 3 after intravitreal injection but not at day 7 when complement levels returned to normal. In group 2 (intravitreal injection of 102 organisms), bacterial counts were significantly higher in the vitreous of experimental guinea pigs versus control guinea pigs only at day 1 with no statistically significant differences thereafter. In group 3 (intravitreal injection of 150 bacteria), there were no significant differences in bacterial counts in the vitreous of experimental versus control guinea pigs. Our results in group 1 suggest that partially decomplemented guinea pigs show impaired host defense to P. aeruginosa and that this defense is restored as complement levels return to normal. Intravitreal injection of higher numbers of P. aeruginosa as in a group 3 overwhelms and obscures any beneficial effect of the complement system on host defense. PMID- 4030254 TI - Preparation of a uveitogenic peptide by chymotryptic digestion of bovine S antigen. AB - Limited proteolysis of bovine S-antigen with alpha-chymotrypsin resulted in the accumulation of three peptides of MW 24,000, 16,000, and 12,000 daltons, respectively. By ELISA (enzyme-linked immunosorbent assay), MW 24,000 peptide was found to react with anti-S antibodies, but the other two peptides did not react with the antibodies under the assay conditions. The reactive peptide was separated from the smaller peptides by gel filtration on Sephadex G-75 and Sephadex G-50. When the MW 24,000 peptide was injected into Lewis rats, severe to mild uveitis was produced in all injected animals. The results indicate that the pathogenic determinant is on the MW 24,000 peptide. PMID- 4030255 TI - Ultrastructural pathology of S-antigen uveoretinitis. AB - The morphology of S-antigen-induced uveoretinitis in guinea pigs has been studied using transmission electron microscopy. Purified bovine retinal S-antigen was shown to produce a focal chorioretinitis, characterized by selective damage to the outer retina and, almost exclusively, a mononuclear cell infiltration of the choroid and retina. Even at high doses, extensive rod outer segment damage was associated predominantly with lymphocytic and mononuclear cell infiltration. A single immunizing injection of S-antigen was sufficient to produce a chronic ocular inflammation lasting many months. Focal lesions evolved rapidly and reached an end-stage within days to weeks. Accordingly, eyes examined at any time during the disease contained areas of normal retina coexistent with fibrotic lesions. With time, the number of advanced or end stage lesions became more frequent, thereby involving a more widespread area of the retina. Examination of early stage lesions suggest that the rod outer segment is the target for immune damage in this disease, but the mechanism of damage remains to be elucidated. PMID- 4030256 TI - Langerhans cell alterations in the guinea pig cornea. AB - Langerhans cells (LC) are found in virtually all epithelial surfaces, but are rare or absent in the central cornea. LC migration into the cornea can be induced by several different stimuli. The authors studied LC in guinea pig corneal epithelium after: (1) suture placement; (2) suture removal; (3) UV-A irradiation; and (4) UV-C irradiation. Corneal LC markedly increased after suture placement during a 35-day observation period, and decreased by one-half during a 21-day observation period when sutures were removed. Suture-induced corneal LC decreased after UV-A irradiation, but increased after UV-C irradiation. These results demonstrate that ocular LC can be altered by nonimmunologic perturbations of the cornea. PMID- 4030257 TI - Measurement of centripetal migration of normal corneal epithelial cells in the mouse. AB - Fine punctate marks were made in normal corneas of mice using a needle rotating in a mixture of India ink and thorium dioxide. After 7 days, the marker was visible in the stroma and also in epithelial cells which had moved away from the stromal marks and towards the center of the cornea. The mean distance between these labels at the end of 7 days was 94 microns +/- 14 (SEM). The median distance migrated was about 17 microns per day. This figure represents the distance through which superficial and wing cells had migrated; the distance migrated by basal cells was not determined. PMID- 4030258 TI - Experimental granulomatous uveitis: an electron microscopic study of pigment containing giant cells. AB - An experimental granulomatous uveitis in the Brown Norway rat is characterized by large numbers of giant cells and epithelioid cells containing uveal pigment. Ultrastructurally, the epithelioid cells and the giant cells exhibited melanosomes and individual melanin granules in the absence of phagocytic membranes and compound pigment granules. These observations support the view that the pigment containing giant cells may develop from uveal melanocytes. PMID- 4030259 TI - The parallels between diagnostic and therapeutic research. PMID- 4030260 TI - Systematic evaluation and increased structure in a radiology elective. AB - Diagnostic radiology is expanding, playing an increasingly central role in patient care, which heightens the importance of radiology teaching in undergraduate medical education. This study examined the impact of increased structure and systematic evaluation on student performance in a radiology elective. The evaluation protocol included premultiple and postmultiple choice examinations (70 questions each), a film interpretation quiz (ten films, 20 questions), faculty assessment of a student oral case presentation, and student evaluations of the elective experience. The relationships among the evaluation techniques, as well as differences in class level and course ratings were also examined. Two different treatment groups were studied. Group 1 was given general objectives and information regarding availability of recommended resources, including self-learning materials for the elective, didactic seminars, and viewbox exposure. Group 2 was given specific written instructional objectives, a structured schedule for viewing the self-learning materials, and the same seminars and viewbox exposure. The statistically significant higher performance of the structured group suggests that medical students achieve the objectives of an elective better when learning activities are well defined, structured, and systematically evaluated. In addition, those students receiving the structured experience rated the radiology elective more favorably. PMID- 4030261 TI - Characterization of changes in coronary blood flow during the first six seconds after intracoronary contrast injection. AB - With current interest in digital and densitometric angiographic techniques for evaluating coronary blood flow (CBF), the immediate effects of intracoronary contrast injections on CBF are important to establish. We investigated the effects of ECG-gated intracoronary injection of contrast on CBF with different injection rates (1-6 cc/sec), volumes (1/2-6 cc), and contrast concentrations (1/2, full strength). Sixteen open-chest dogs were instrumented with electromagnetic flow probes on the left anterior descending artery. During intracoronary injections of contrast, a characteristic decrease in coronary blood flow to approximately 45% of preinjection levels was seen an average of 1.9 seconds after intracoronary contrast injection. The timing of the depression in coronary flow was most influenced by the rate of contrast injection, and the magnitude of depression in flow was influenced by both the volume and concentration of the contrast injection. Angiographic techniques using the first 6 seconds after injection to obtain CBF measurements should take these characteristic changes into account to avoid possible errors. PMID- 4030262 TI - A stochastic interpretation of thallium myocardial perfusion scintigraphy. AB - A method is presented for the quantitative interpretation of thallium-201 myocardial perfusion studies. The data are planar images collected immediately following the stress injection, and 4 to 6 hours later. Data analysis consists of preprocessing, including thresholding of the original data, and data reduction using a variant of the circumferential profile methods. The profiles are subdivided into segments, and for each segment the difference between the norm and the actual data is computed. This difference is a quantitative symptom, whose size is assumed to be related to the probability of having the disease. The relationship between the size of the symptom in each of nine segments (three segments/view in three views) and the probability of disease is expressed in a table in which for 30 diseases (combinations of vascular lesions) the sensitivity for each of the nine symptoms is described as a Gaussian function whose average and standard deviation are computed from previous validated cases. Using an arbitrary prevalence, the post-testing probability can then be computed using Bayes' formula sequentially. The sensitivities, however, are not expressed as a binary function of the presence or absence of a symptom, but as a distribution function defined by experience. The method is sensitive for the detection of isolated left anterior descending disease (100%) and triple vessel disease (96%). When specific combinations of vascular lesions are recognized the specificity increases from 79% (when unspecified abnormalities are recognized) to 87% when left anterior descending disease or triple vessel disease is recognized.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4030263 TI - Computed tomographic evaluation of lesions in the thoracic apex. AB - Fifty patients with clinically suspected lesions of the chest apex underwent computed tomography (CT) and plain film (PF) examinations in an attempt to define the underlying etiology as benign or malignant. CT was slightly more sensitive in diagnosing malignancy (90%) compared with PF (77%), with a higher predictive value of a negative test (85% vs. 70%), although the differences were not statistically significant. The specificity and predictive value of a positive test were similar for CT and PF. CT's advantage was better elucidation of the soft tissues of the chest apex. CT provided additional information beyond PF in 17/20 patients with benign conditions and in 29/30 patients with cancer. In 21 of these 29 cancer patients, CT findings significantly altered subsequent management. PMID- 4030264 TI - A CT technique to evaluate the development of carcinogen-induced neoplasia in the rat liver. AB - Hepatocellular neoplasms, including neoplastic nodules (NN), are the most commonly induced tumors resulting from chemical carcinogen evaluation. Our objective was to image neoplastic nodules using computed tomography. In a preliminary study using rats with diethylnitrosamine (DEN) induced tumors, lesions smaller than 1.5 cm were difficult to identify by CT. Since NN do not take up excess iron whereas normal liver does accumulate iron, we studied iron as a CT contrast material. Hemochromatosis was induced in 15 control rats by subcutaneous injections of iron dextran. A linear increase in iron-loading dose produces a linear CT liver enhancement (r = 0.97): 68, 80, 84, 94, and 104 HU at 0, one, two, four, and six weeks, respectively. No loss of enhancement was noted ten weeks later. Rat hepatic tissue was chemically analyzed after a similar iron loading regimen. The iron concentration (microgram/g hepatic tissue) progressively increased during the first four weeks of loading and remained stable for three weeks following iron-loading. Four animals that had been given DEN and iron were examined by CT scanning to detect small NN. Iron-enhanced CT allowed the visualization of small lesions (less than 5 mm). Histopathologic sections confirmed a homogeneous pattern of iron uptake in normal liver with a deficiency of iron in NN. We conclude that CT scanning following iron-loading is a noninvasive method to detect small nodules and may provide a method to study the progression or regression of small liver nodules in rodents. PMID- 4030265 TI - The importance of the motion of water for magnetic resonance imaging. AB - Since the water content of all soft tissues is about the same, contrast in magnetic resonance imaging depends principally on the parameters that govern nonequilibrium behavior of the nuclear spin system of the water protons of tissue, the longitudinal and transverse relaxation rates 1/T1 and 1/T2. A fundamental understanding of the determinants of both 1/T1 and 1/T2 at a cellular level, and ultimately at a molecular level (so that contrast can be optimized and perhaps manipulated), will require a model of the behavior of water that describes the dynamics of the motion of water molecules throughout tissue. A particular model is presented here, one in which tissue water is relatively free to diffuse randomly throughout the intracellular and extracellular regions of tissue, colliding with cellular and subcellular constituents along the way; this motion dominates 1/T1 at higher fields. When not in actual contact with interfaces, ie, within about 5 A of a macromolecular surface, the thermal motion of the water molecules is not influenced by the interfaces, but is altered slightly by the presence of solute macromolecules. However, this small difference is amplified 10(6)-fold, roughly the ratio of the macromolecular to solvent molecular weights, by a mechanism previously named the "slosh effect"; this effect dominates 1/T1 at low fields, and 1/T2 at all fields. It is shown how the foregoing view of tissue water follows quite naturally from NMRD profiles (measurements of the magnetic field dependence of 1/T1 of water protons) of a wide variety of protein solutions and samples of tissue, both native and containing added paramagnetic (Mn2+)ions.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4030266 TI - Quantitative computed tomography for spinal density measurement. Factors affecting precision. AB - Quantitative computed tomography (QCT) was performed in duplicate on 84 patients to test the short-term precision of the technique. Statistical analysis of the data revealed that precision was not a function of spinal density. It appeared to be worse in osteopenic individuals only when expressed as a percentage. Precision was slightly better in male than in female patients. There is a 90% likelihood that a duplicate measurement will fall within 20 CT units of the first determination in female patients and within ten units in male patients. PMID- 4030268 TI - Increasing participation by medical students. PMID- 4030269 TI - Adolescent depression and suicide. PMID- 4030267 TI - Collagen-induced arthritis in rats. Assessment by serial magnification radiography. AB - Serial whole body and lateral hindpaw magnification radiographs were obtained on 15 rats with collagen-induced arthritis. The radiographs were evaluated for findings of inflammatory arthritis. Soft tissue swelling and juxta-articular osteopenia usually developed two weeks after immunization. The swelling remained stable for the remaining seven weeks of the study, but the osteopenia apparently improved. Three weeks after immunization, erosions and periostitis began to develop in ten of the rats. These latter radiographic changes rapidly worsened over the next three weeks and then stabilized. The most frequent and severe changes were seen in the intertarsal, tibiotalar, and metatarsophalangeal joints. The toes, forepaws, and knees were infrequently involved. Other peripheral joints and the axial skeleton were spared. Five rats developed soft tissue swelling but had no articular erosions or periostitis. Serial radiography has potential usefulness for monitoring the effects of treatment in this experimental model for inflammatory arthritis. PMID- 4030270 TI - Neonatal posterior fossa hemorrhage. PMID- 4030271 TI - Liberal arts and the preparation for medicine. PMID- 4030272 TI - Third generation cephalosporins. PMID- 4030273 TI - AIDS concerns in Iowa: an interview with Laverne Wintermeyer. PMID- 4030274 TI - Acquired immunodeficiency syndrome in a small community. PMID- 4030275 TI - Retrovirus-like particles in Hodgkin's disease. PMID- 4030276 TI - Diuretic update. PMID- 4030277 TI - Calculating available dietary iron. PMID- 4030279 TI - Serum theophylline--a mandatory measurement in the control of therapy? PMID- 4030278 TI - Vascular responses to intravenous catecholamines in hands and forearms with normal and with increased skin blood flow. PMID- 4030280 TI - Use of oxygen driven nebulizer delivery systems for beta-2 agonists in chronic bronchitis. PMID- 4030282 TI - Irish Society of Gastroenterology. 21st anniversary year meeting. Abstracts. PMID- 4030281 TI - Large bowel infarction and ergometrine: a possible relationship. PMID- 4030283 TI - Tuberculosis in animals. PMID- 4030284 TI - The epidemiology and control of tuberculosis. PMID- 4030285 TI - The role of the surgeon in the treatment of pulmonary tuberculosis. PMID- 4030286 TI - Chemotherapeutic agents in pulmonary tuberculosis with special reference to isoniazid-ethambutol continuation therapy. PMID- 4030287 TI - Management of tuberculosis in Ireland today. PMID- 4030288 TI - Tuberculosis undefeated. PMID- 4030289 TI - Anthropometry and body image in a selected sample of adolescent girls. PMID- 4030290 TI - Risk factors and perinatal problems in small for gestational age pregnancies. PMID- 4030291 TI - Gynaecological microsurgery--a review of 43 cases. PMID- 4030292 TI - Severe hypertension following left ventriculography. PMID- 4030293 TI - Studies of the epidemiology of preinvasive and invasive carcinoma of the uterine cervix in Ireland. PMID- 4030294 TI - Childhood autism: 0-35 years. PMID- 4030296 TI - Spontaneous perforation of the cervical oesophagus. PMID- 4030295 TI - Coeliac disease in children: problems in diagnosis and management. PMID- 4030297 TI - Relapsing polychondritis--case report. PMID- 4030298 TI - Abstracts of papers presented at the meeting on "Progress in polyamine research" of the Italian Study Group of the Italian Biochemical Society. April 26-27, 1984, Messina. PMID- 4030299 TI - Variables affecting short-term prognosis in completed stroke. AB - After a review of the prognostic factors affecting the short-term outcome of completed stroke, the implications for the design of stroke treatment trials are discussed. These concern stratification variables, patient selection, sample size estimation, length of follow-up, and measures of outcome. Potential variables for stratification are type of stroke (i.e. infarct or hemorrhage), age of the patient, level of consciousness, and preceding hypertension and heart disease. PMID- 4030300 TI - Cluster analysis of cognitive performance in elderly and demented subjects. AB - 48 elderly normals, 14 demented subjects and 76 young controls were tested for basic cognitive functions. All the tests were quantified and could therefore be subjected to statistical analysis. The results show a difference in the speed of information processing and in memory load between the young controls and elderly normals but the age groups differed in quantitative terms only. Cluster analysis showed that the elderly and the demented formed two distinctly separate groups at the qualitative level, the basic cognitive processes being damaged in the demented group. Age thus appears to be only a risk factor for dementia and not its cause. It is concluded that batteries based on precise and measurable tasks are the most appropriate not only for the study of dementia but for rehabilitation purposes too. PMID- 4030301 TI - Involutional dementias: new perspectives. AB - 13 patients with psycho-organic syndrome (POS) and 10 patients with dementia (senile, Alzheimer, multi-infarct) were treated with drugs considered to influence the neuronal turnover of acetylcholine (Phosphatidylcholine, piracetam, S-adenosylmethionine) for 30 days and compared in respect of CSF ACh levels, reaction times to simple visual stimuli (TRS-V) and to simple hearing stimuli (TRS-H) and scores on the Sandoz Clinical Assessment Geriatric (SCAG) rating scale. The POS patients presented higher CSF ACh levels, shorter TRS-V and TRS-H times and lower SCAG scores than the demented patients before treatment. During treatment the CSF ACh values fell in the POS but not in the demented patients. All the other values improved in both groups but more markedly in the POS group. The CSF ACh variations in the latter appear to correlate with the variations in TRS-V and TRS-H times and SCAG scores. The monitoring of CSF ACh would seem to be useful in assessing both the degree of decline in dementia and the possibilities of treatment in individual patients. PMID- 4030302 TI - Comparison of cervical SEPs on median, radial and ulnar nerve stimulation. AB - Cervical responses (SEPs) to stimulation of the median, radial and ulnar nerves were studied in 9 healthy subjects. In recordings from e Cv7 electrode referenced to a scalp electrode P11 presented a bilobed (P11a + P11b) profile for all three nerves whereas from Cv2 only P11b appeared as a rule. P11a and P11b were more distinct in the ulnar than in the median and radial nerves. The P11 onset-P13 onset interval was virtually the same for the radial and median nerves and approximately 0.4 msec longer for the ulnar nerve. This difference probably represents the Cv8 to Cv6 intramedullary conduction time. An exact evaluation of P11 onset is possible only in low cervical recordings, though the P11 peak may be a useful landmark when recording from Cv2. P11a would appear to originate at (or near) spinal entry, P11b high in the cervical cord and P13 at supraspinal level. PMID- 4030303 TI - Brainstem auditory evoked potential (BAEP) abnormalities in subjects with craniovertebral malformations. AB - We report the data on 42 monaural BAEP recordings from 10 patients with craniovertebral malformations. Of 8 preoperative recordings from 3 patients 6 showed an increased I-III interpeak latency (IPL). Of 28 recordings taken shortly (1-12 months) after surgery 21 showed an abnormal I-III IPL. On the other hand, of 6 recordings from 3 patients 20 years after surgery 5 were in the normal range and 1 showed an abnormal I-III IPL. Although the most important site of craniovertebral malformations is the cervicomedullary junction, the results reported suggest unilateral or asymmetrical bilateral involvement of the medullary-pontine junction, on the evidence of BAEP wave III, in a large proportion of patients with these malformations. PMID- 4030304 TI - Microsurgical treatment of intracranial aneurysm in the elderly. AB - Microsurgery for supratentorial aneurysm was performed in 19 patients over the age of 65 with good results in 74%. Mortality and complications are discussed in the light of the preoperative neurological status and general condition. The indications for surgery are outlined. PMID- 4030305 TI - Computerized tomography in CO poisoning. AB - In a case of CO poisoning CT scanning revealed bilateral low density areas in the globi pallidi, associated with diffuse hypodensity of the white matter of the cerebral hemispheres. Serial scanning threw some light on the possible mechanism involved and appears to support the hypothesis of necrotic damage of vascular origin following brain edema. An attempt is made to correlate the pattern of CT abnormalities with clinical evolution. PMID- 4030306 TI - A case of Kufs disease with abnormal pallidonigral iron deposit. AB - The clinical, neuropathological and ultrastructural features of a case of Kufs disease (Meyer basal ganglia form) are reported. In the present case, besides the typical lesions of Neuronal Ceroid-Lipofuscinosis, and increased iron reaction at pallidonigral level was detected histochemically. The significance of the last finding is discussed. PMID- 4030307 TI - Polygraphic-television recording in a case of syncope. AB - In a case of loss of consciousness presenting diagnostic difficulties, the syncopal nature was determined only with the help of combined polygraphy and closed circuit television recording. PMID- 4030308 TI - Aqueductal stenosis following mumps virus infection. Case report. AB - A case of aqueductal stenosis following mumps infection is reported, to the authors' knowledge the 12th case in the literature. The pathogenetic events are discussed and the literature reviewed. PMID- 4030309 TI - The role of the medical home in child abuse prevention and positive child development. PMID- 4030310 TI - The 1% law. PMID- 4030311 TI - Spurious. PMID- 4030312 TI - Migraine-cluster headache syndrome. PMID- 4030313 TI - Complicated migraine and cerebral angiography: a report of an unusual adverse reaction. PMID- 4030314 TI - Unnecessary dental treatment of headache patients for temporomandibular joint disorders. PMID- 4030315 TI - Neck tongue syndrome. PMID- 4030316 TI - Plasma methionine enkephalin levels. A biological marker for migraine? PMID- 4030317 TI - Common migraine attack: platelet modifications are mainly due to plasma factor(s). PMID- 4030318 TI - Non-migrainous headache and transient neurological deficits. PMID- 4030319 TI - Stress, mathematics and migraine. PMID- 4030320 TI - In-service training. PMID- 4030321 TI - Opportunistic cervical cytology screening in the Dundee catchment area. PMID- 4030322 TI - A study of antenatal vitamin and iron supplementation in Glasgow. PMID- 4030323 TI - Medical staffing in the National Health Service in Scotland. PMID- 4030324 TI - The impact of psychogeriatric day care on the patient's supporting relatives. PMID- 4030325 TI - Cognitive commitments in health services marketing. AB - Armed with valid information about what people expect, health care organizations can make commitments to current and prospective patients, thereby increasing their marketing success and improving patient satisfaction. PMID- 4030326 TI - Hospital receptivity to market competition: image and reality. PMID- 4030327 TI - Financial incentives for middle managers: pilot program in an inner city, municipal teaching hospital. PMID- 4030328 TI - Quality circles: the myth and reality of hospital management. AB - Although quality circles have been successfully introduced into U.S. hospitals, they have not fared well in Japan. In light of the fact that Japanese hospitals have within their organizational structures many elements considered a precondition for the success of quality circles, their hesitance in adopting this innovation deserves attention. It is useful to examine the reasons quality circles may be more feasible in the United States than in Japan. PMID- 4030329 TI - The failure of the group model: a case study. AB - In 1975 the Cincinnati Board of Health introduced group practice as a way of delivering health care to the indigent. In spite of encouraging initial results, five years later the model failed. Its failure offers lessons and useful insight to health care administrators. PMID- 4030330 TI - HCMR interview: John R. Mannix. Interview by Montague Brown. PMID- 4030331 TI - Comparison of Ca-DTPA and Zn-DTPA in removing 234Th from the rat. AB - The relative effectiveness of Ca-DTPA and Zn-DTPA as a function of the dose, number of doses and time of their administration in removing 234Th that had been administered as the citrate or nitrate from various rat organs was investigated. With a single early treatment (1.5 min after intravenous injection of 234Th), Zn DTPA was clearly less effective than Ca-DTPA over the whole dose range (30 mumol/kg body weight-1000 mumol/kg body weight) tested. In the skeleton, 1000 mumol Zn-DTPA/kg removed as much 234Th (about 50%) as 30 mumol Ca DTPA/kg. Prompt treatment with 100 mumol Ca-DTPA/kg body weight diminished the skeletal 234Th content by about 70%; but when it was delayed by 6 h or 4 d, the 234Th content was reduced by only about 20% and 10%, respectively. The effect of DTPA in the bone was independent of 234Th compound, while in the soft tissues 234Th injected as nitrate was less affected than the citrate. The effect of DTPA was potentiated when treatment was repeated; the end effect was dependent on the time of the first DTPA injection and on the total number of doses. Thus, about 90% and 50% less 234Th was found in the bones after repeated treatment started at 1.5 min and 4 d after administration of 234Th, respectively. Under the conditions of a delayed repeated treatment, Ca-DTPA and Zn-DTPA were equally effective. PMID- 4030332 TI - Effect of Zn-DTPA therapy on the maternal transfer of 241Am or 237Pu to young mice. AB - Newborn mice exposed to 241Am or 237Pu during gestation and whose mothers were given Zn-DTPA at various times before parturition contained less radioactivity than comparable newborn mice given identical 241Am or 237Pu exposure without Zn DTPA treatment of the mothers. There was no net increase in radionuclide transfer from mothers to unborn young as a result of maternal administration of Zn-DTPA, regardless of the pregnancy stage during which the radioactivity and decorporation treatments were given. Administration of 241Am followed after three days by extended Zn-DTPA therapy resulted in lower fetal content of radioactivity in litters conceived long after or soon after maternal exposure to 241Am. These data indicate that the risk from Am and Pu to unborn young can be reduced by Zn DTPA treatment of the pregnant mother and of the female who becomes pregnant subsequently. This information may prove to be of significance with the increasing probability of Am or Pu exposure to women in the nuclear industry who could be pregnant at the time or who may conceive a child in the future. PMID- 4030333 TI - Occupational radiation exposures in Taiwan, 1962-1983. AB - This paper presents an updated compilation of occupational radiation exposures in Taiwan, Republic of China, for the years 1962-1983. The highest collective dose equivalent occurred in 1981 and was estimated to be 535.318 man-rem, and the average measurable dose equivalent per worker is about 0.25 rem in the same year. All data analyzed were plotted on log-probability paper. A brief prospectus on the health implications of the annual occupational dose equivalents is also provided, using the year 1981 as an example. PMID- 4030334 TI - Effect of air-scattered beta particles on instrument and dosimeter response. AB - Air-scattered beta particles are responsible for many of the inaccuracies encountered when readings are obtained with many types of beta survey instruments and personnel dosimeters. The ratio of beta particles scattered at various angles to beta's coming directly from the source increases as the distance from the source increases. This ratio, at a given distance from the source, is also a function of the beta energy, becoming larger for lower-energy beta sources. Changes in this ratio cause the response of beta instruments to have an apparent change in the directional response. These air-scattered beta particles are also responsible, in many cases, for a part of the apparent decrease in the efficiency of beta survey instruments when detecting low-energy beta sources. Air-scattered beta's also cause personnel dosimeters, which are not properly designed to detect them, to have responses that are low. We give experimental results to confirms the above effects. Design changes to survey instruments and dosimeters are suggested that would eliminate the errors created by the failure of the instruments to detect these air-scattered beta particles. PMID- 4030335 TI - Measurement of absorbed dose from radionuclide solutions mixed intimately with the FBX dosimeter. AB - Chemical dosimeters are used widely for accurate measurement of large radiation doses due to external beam irradiation from radionuclide sources and from particle accelerators. Their use for measurement of absorbed doses from radioactive solutions mixed in the dosimeter solution was reported as early as 1952, but the large activities needed to produce suitable absorbance values in the relatively insensitive dosimeters of that time discouraged further work. This manuscript reports the results of an investigation into the suitability of the ferrous sulfate-benzoic acid-xylenol orange (FBX) dosimeter for measurement of small absorbed doses caused by radionuclide solutions mixed with the dosimeter solution. The FBX dosimeter exhibited a linear dose response as a function of activity for two common radiopharmaceuticals, 99mTc sodium pertechnetate and 131I sodium iodide. Conditions under which the FBX dosimeter may be used with radionuclide solutions were studied and were found to be amenable to routine use by laboratories possessing relatively unsophisticated instrumentation. That any radionuclide could be studied using this dosimeter appears likely. PMID- 4030336 TI - Efficiency estimation for detecting U alpha particles in solid-state nuclear track detectors. AB - The detection efficiencies of solid-state nuclear track detectors, made with cellulose nitrate materials (LR-115 II) or allyl diglycol carbonate (CR-39) were investigated. Detection efficiency for a surface alpha source was experimentally obtained by changing the dimensions between the detector and the source, while alpha-particle incident efficiency was calculated. The ratio of the detection efficiency to the incident efficiency was then determined. It was confirmed that the ratio for LR-115 II was dependent on energy, but for CR-39 the ratio showed almost no dependency. Considering the relationship between solid absorber thickness and detection efficiency of the surface alpha source, detection efficiencies of U in various metals were estimated. The efficiency for U contained in Al and Fe was proposed as 16% for LR-115 II and 22% for CR-39. Using these efficiencies, amounts of U in some Al and Fe ingots were determined. These agreed with concentrations obtained by neutron-activation analysis with deviations of less than 15%. PMID- 4030337 TI - Enhanced nuclear radiation from camera lenses. PMID- 4030338 TI - Iodine-129 in mammalian thyroids in the Federal Republic of Germany. PMID- 4030339 TI - The metabolism and decorporation of Pu after inhalation of the tributyl phosphate complex by the rat. PMID- 4030340 TI - Plutonium fallout at Fayetteville, AR. PMID- 4030341 TI - The distribution of a pulsed very low frequency electric field around video display terminals. PMID- 4030342 TI - Krypton-85 purge at Three Mile Island: a comparison of measured and calculated surface air concentrations. PMID- 4030343 TI - Use of sintered magnesium borate thermoluminescent dosimeters for low dose measurements. PMID- 4030344 TI - High thermoluminescent dosimeter readings outside a medical accelerator. PMID- 4030345 TI - Confirm or deny: nuclear submarine workers at Portsmouth Naval Shipyard had excess leukemia. PMID- 4030347 TI - [Microvascular reconstruction of peripheral blood vessel occlusions in the hand and fingers]. PMID- 4030348 TI - [Comparison of traditional and microsurgical methods in reconstructive surgery of the limbs]. PMID- 4030349 TI - [Disaster medicine--a new medico-surgical discipline]. PMID- 4030350 TI - [Vascular surgery on sick tissue]. PMID- 4030346 TI - Low-level radiation, malignant disease, extrapolation and 'official science'. PMID- 4030351 TI - [Musculo-cutaneous flaps in general surgery]. PMID- 4030352 TI - [Mechanical properties of Ilizarov's external fixator]. PMID- 4030353 TI - [Risk of colorectal cancer after cholecystectomy]. PMID- 4030354 TI - [Stoneless necrotizing cholecystitis in patients with polytrauma]. PMID- 4030356 TI - The initial evaluation of the polytrauma. PMID- 4030355 TI - [Left-open abdomen. Indications and experiences]. PMID- 4030357 TI - [Jejunal diverticulitis, a rare cause of acute abdomen]. PMID- 4030359 TI - [Reconstruction of the breast after mastectomy]. PMID- 4030358 TI - [Scapular flap]. PMID- 4030360 TI - [Osteosynthesis of the phalanges]. PMID- 4030361 TI - [Bone blood supply after change of implant]. PMID- 4030362 TI - Bone loss following plate fixation of fractures? Quantitative determination in human tibiae using computed tomography. PMID- 4030363 TI - [Incidence, treatment and late results of fresh and old injuries of posterior cruciate ligaments]. PMID- 4030364 TI - [Stress relief of the osteosynthesis plate by an interfragmentary plate traction screw]. PMID- 4030365 TI - [Plastic surgery of the anterior cruciate ligament: late results after 5 different reconstruction procedures]. PMID- 4030366 TI - [Fibular injury of ligaments of the upper part of the ankle joint. Contribution to the roentgen diagnosis]. PMID- 4030367 TI - [Transarticular fracture of the calcaneus. Widening approach and technic of reposition]. PMID- 4030368 TI - [Surgical treatment of peripheral and central injuries of the talus]. PMID- 4030369 TI - [Measurement of chemiluminescence in diluted whole blood for the determination of granulocyte function in the perioperative period]. PMID- 4030370 TI - [Surgical treatment of diverticulitis]. PMID- 4030371 TI - [Diverticulitis--pathophysiological aspects and surgical therapy]. PMID- 4030372 TI - [Intraoperative wound irrigation with a new local antiseptic]. PMID- 4030373 TI - [10-year experience in malignant struma surgery: relevant and irrelevant factors in the prognosis]. PMID- 4030375 TI - [Biliary bacteriology in clinical use]. PMID- 4030374 TI - [Late follow-up of venous thrombosis of the thigh and pelvis using radionuclide phlebography]. PMID- 4030376 TI - [Replacement of the cervical esophagus by a free small intestine transplant in swine]. PMID- 4030377 TI - [Experiences with the clinical use of hot air jet coagulation]. PMID- 4030378 TI - [Correction of rectovaginal fistulas]. PMID- 4030379 TI - Compound heterozygosity for two genotypes of alpha-thalassemia-2: hematological, biosynthetic and DNA studies. AB - Hemoglobin and DNA gene analyses were carried out in two Black Canadian families. In Family Q, both the parents and the brother were found to be heterozygotes for alpha-thalassemia-2 with the following alpha-genotypes: -alpha 3.7/alpha alpha, alpha 4.2/alpha alpha and -alpha 4.2/alpha alpha, respectively. In Family C, the mother was found to be a homozygote for alpha-thalassemia-2 with the alpha genotype of -alpha 3.7/-alpha 3.7. In both families, the propositi were compound heterozygotes for alpha-thalassemia-2 with the alpha-genotype of -alpha 3.7/ alpha 4.2. The propositus in Family C was also a sickle cell trait carrier. The usefulness of DNA gene analyses in family studies of hemoglobinopathy was discussed. PMID- 4030380 TI - Distributions of hemoglobins A and S among erythrocytes of heterozygotes. AB - The recently developed capability to separate and quantify each of several proteins concurrently in single red cells presents an opportunity to test for biological variations in intercellular distribution of a protein as well as the extent of correlation between quantities of gene products derived from a single cell genome. In this preliminary study, erythrocytes from 30 sickle trait subjects were subjected to single cell electrophoresis and the resulting hemoglobin electropherograms were scanned by a recording densitometer. There was found to be heterogeneity among subjects in the form of the intercellular distribution of Hb S fraction, as tested by g statistics for skewness and kurtosis. Additionally, in all subjects there was statistically significant correlation between relative quantities of cellular Hb A and Hb S as measured concurrently in the same cell. These observations provide a basis for future research on the hypothesis that the form of the distribution of hemoglobin among erythrocytes is a heritable variable. PMID- 4030381 TI - Hemoglobin Handsworth or alpha2 18(A16)Gly----Arg beta2 in a Saudi newborn. PMID- 4030382 TI - Hemoglobin Cocody [beta 21 (B3)Asp----Asn] hematologic aspects of heterozygosity and of Hb Cocody/beta +-thalassemia. PMID- 4030383 TI - Hemoglobinopathies in Turkey. PMID- 4030384 TI - International Hemoglobin Center policies--IHIC. PMID- 4030385 TI - Three-dimensional vascular architecture of the dog heart as revealed by injection replica scanning electron microscopy. PMID- 4030386 TI - Studies with the total artificial heart using sheep as an adult animal model. PMID- 4030387 TI - In vitro susceptibility of Mycobacterium fortuitum complex to cephem antibiotics. PMID- 4030388 TI - Proceedings of a symposium on progress in general, applied and diagnostic histochemistry. Modra, Czechoslovakia, 12-15 April, 1984. PMID- 4030389 TI - Cell surface morphology of the morphogenetically active system of the embryo after treatment with tunicamycin, a glycosylation blocking drug. PMID- 4030390 TI - Cytochemical and immunological profiles of fresh and cultured leukaemic cells. PMID- 4030391 TI - Lysosomes of the rat pituitary intermediate lobe. PMID- 4030392 TI - Detection by the PAP technique of lysozyme-containing synoviocytes and their quantity in rheumatoid arthritis and osteoarthrosis. PMID- 4030393 TI - Placental alkaline phosphatase in benign and malignant endometrium. AB - The presence of placental alkaline phosphatase has been demonstrated immunohistochemically using a monoclonal antibody, in frozen sections of human endometrium. The enzyme is present in glandular epithelium, but is found most commonly in the surface epithelial layer throughout the menstrual cycle. It has also been demonstrated in malignant endometrial epithelium in eight out of twelve patients. PMID- 4030395 TI - Quantitative analysis of collagen, protein and DNA in fixed, paraffin-embedded and sectioned tissue. AB - Modifications and adaptations of chemical techniques have been used to quantitate hydroxyproline (collagen), total protein and DNA in fixed, paraffin-embedded and sectioned tissue. The assays are rapid and sensitive to between 0.1 and 1.0 micrograms of each of the three components. Values for the ratio of collagen to total protein or collagen per DNA obtained from sectioned material are the same as values derived from fresh or fixed starting material. Depending on the tissue and the sample size, as little as three to five 5 micron thick sections can be analysed for these three components. The ratios of collagen per total protein or collagen per DNA are given for several murine tissues. The assay of these components in tissue sections will allow a more precise correlation between histological appearance and the quantitative biochemical changes that may accompany many pathological disorders. The techniques are particularly useful in retrospective studies where the experimental material may be en bloc. PMID- 4030394 TI - Lectin histochemistry of complex carbohydrates in human cervix. AB - Complex carbohydrates in the human cervix were studied histochemically using lectins conjugated to horseradish peroxidase and correlated procedures. Stratified squamous epithelium of the exocervix and columnar epithelium of the endocervix in some, but not all specimens showed staining for terminal alpha-N acetyl-D-galactosamine, alpha-D-galactose, beta-D-galactose and alpha-L-fucose. The staining for alpha-N-acetylgalactosamine and alpha-galactose, the terminal sugars in blood group A and B antigens respectively, corresponded to a large extent with ABO blood type. One exception was the lack of staining for terminal alpha-N-acetylgalactosamine in endocervical secretions in three of nine blood type A patients. A second exception was the staining for terminal alpha-galactose in endocervical secretions in about half of blood type O and A specimens. The type and amount of glycoprotein formed by endocervical columnar cells differed according to location in superficial compared with deep portions of the glands and according to location at the junction with exocervix compared with the more internal regions. Staining of endothelial cells for blood group A and B antigens was confined to subjects of blood type A and B respectively, although three of nine type A specimens showed no lectin reactivity for group A antigen. Endothelial cells evidenced affinity for Ulex europeus I agglutinin demonstrative of fucose in all specimens. Mast cells disclosed lectin affinity consistent with the presence of terminal or internal mannose or N-acetylglucosamine residues. Two blood type O specimens were examined with conjugated lectins at the ultrastructural level. Secretory granules stained for content of terminal alpha galactose, beta-galactose and fucose. These results support and concur with biochemical studies of complex carbohydrates in human cervical tissues. They reveal, in addition, the location of the blood group antigens in the human exocervix and endocervix and the marked heterogeneity among endocervical columnar cells in glycoprotein production. PMID- 4030396 TI - Histochemical demonstration of monoaminergic and cholinesterase-positive nerve fibres in regenerating rat submandibular gland autografts. AB - A cholinesterase localization method and a monoamine histofluorescence technique were used to locate nerve fibres in regenerating rat submandibular gland autografts. Experimental rats had a portion of one submandibular gland excised and cut into small fragments which were autografted immediately into the middle one-third of the tongue. Control rats had a portion of one submandibular gland removed and discarded, and their tongues were sham-operated. Seven to ten weeks later, the rats were killed and the tongues were removed, frozen and sectioned in a cryostat. A light microscopical study of the tongue sections subjected to the cholinesterase technique showed that the submandibular gland autografts contained many nerve fibres that exhibited cholinesterase activity. These cholinesterase positive nerve fibres were distributed throughout the autografts. The fibres were associated with the numerous duct-like structures and the less numerous acini. In addition, ultraviolet illumination of tongue sections after treatment with a glyoxylic acid mixture revealed histofluorescent monoaminergic nerves within the autografts. These fibres were less prominent than the cholinesterase-positive fibres and appeared to run primarily along blood vessels within the autografts. The results suggest that autonomic nerves are present within regenerating submandibular gland autografts. PMID- 4030397 TI - Fibre-type specificity and effect of thyroid hormone on glucose 6-phosphate dehydrogenase activity in normal and denervated skeletal muscles of the rat. AB - Glucose-6-phosphate dehydrogenase activity increases following denervation of rat skeletal muscle. The specificity of this effect to muscle fibre type was studied. Basal activity of the dehydrogenase was higher in soleus, a muscle composed predominantly of type I fibres, than in extensor digitorum longus, a muscle composed predominantly of type IIa and b fibres. The enzymatic activity of the soleus was also greater than that of the red (RQ) and white (WQ) portions of quadriceps muscle (predominantly type IIa and type IIb fibres, respectively). Following denervation, glucose-6-phosphate dehydrogenase increased in extensor digitorum longus and RQ, but not in WQ or the soleus. Following chronic treatment of rats with 3,3',5-triiodothyronine, which converts type I muscle fibres to type II, the dehydrogenase activity increased in both denervated soleus and extensor digitorum longus. It is concluded that the effect of denervation on glucose-6 phosphate dehydrogenase activity is selective for type IIa (fast oxidative glycolytic) muscle fibres. PMID- 4030398 TI - Quantitative aspects of the histochemical tetrazolium salt reaction on monoamine oxidase activity in rat liver. AB - The tetrazolium method for the histochemical detection of monoamine oxidase (MAO) activity in rat liver cryostat sections has been tested for its specificity and its possible use in quantification. The tetrazolium salt tetranitro blue tetrazolium is recommended for the localization of MAO activity, rather than nitro blue tetrazolium or BPST [2-(2-benzothiazolyl)-3-(4-phthalhydrazidyl)-5 styryl-tetrazolium] . Hardly any formazan was produced in the absence of the substrate tryptamine and Marsilid, a specific inhibitor of MAO activity, prevented formazan production almost completely. A linear relationship between the integrated absorbance measured with a microdensitometer and either the incubation period or section thickness was obtained. We conclude that the method described in this paper can be used for the quantitative analysis of MAO activity in tissue sections of rat liver. MAO activity was found to be 20-25% higher in the periportal zone of rat liver than in the perivenous zone. PMID- 4030399 TI - Rat prostate gland--a good model for demonstration of ornithine decarboxylase by immunohistochemistry. AB - Ornithine decarboxylase was localized immunohistochemically in paraffin sections of prostate glands of the rat using Sternberger's PAP technique. Two types of immunoreactive cells were detected in the gland epithelium: strongly positive ones and weakly positive ones. Unreactive cells were also present. The functional role of the enzyme in the secretory process of the glands is discussed in the light of these findings. PMID- 4030400 TI - Quantitative correlative proton and electron microprobe analysis of biological specimens. AB - To investigate the possibility of quantitative correlative proton microprobe (PMP) and electron microprobe (EMP) analysis of biological soft tissue, model specimens were analyzed by both techniques. The specimens consisted of freeze dried sections of gelatin containing known concentrations of nickel chloride. Both for PMP and for EMP, the signal was expressed as the ratio of the characteristic intensity and the continuum intensity in a peak-free region of the spectrum. With both techniques, calibration curves (signal versus known concentration) obtained, showed a deviation from linearity at high nickel concentrations. However, a linear relation (correlation coefficient 0.996) was obtained in a plot of EMP signal versus PMP signal. This indicates that quantitative correlative PMP and EMP analysis can be carried out by using the same standard for both analytical techniques. PMID- 4030402 TI - A histochemical study about the involvement of rat liver cells in the uptake of heterologous immune complexes from the circulation. AB - Intravenously injected immune complexes (ICx) composed of bovine serum albumin (BSA) and rabbit anti-BSA were taken up by the liver. Insoluble complexes, made in antibody excess, were rapidly taken up by Kupffer cells and were metabolized within 24 h. Soluble complexes, made in antigen excess, were only partly taken up by Kupffer cells. In addition these complexes were bound, taken up and metabolized by endothelial cells. Until 2 h after injection soluble complexes could also be observed along the microvilli of hepatocytes. No signs of endocytosis in hepatocytes could be observed. It is concluded, that ICx can be taken up by Kupffer cells as well as by endothelial cells. The physical state of the complexes, soluble or insoluble, determines the cell type in which uptake occurs. PMID- 4030401 TI - Differential distribution of 3H dihydrotestosterone and 3H estradiol nuclear binding sites in mouse male accessory sex organs. An autoradiographic study. AB - The distribution of specific nuclear binding sites for androgens and estrogens in the male accessory sex organs of the mouse was assessed by autoradiography with 3H dihydrotestosterone (3H DHT) and 3H estradiol (3H E2). With 3H DHT nuclear labeling differed among the epithelia of the organs. It was high in seminal vesicle and ampullary gland, moderate in ventral prostate, urethral gland, prostatic excretory ducts and the ampulla ductus deferentis, low in dorsal prostate and low or absent in coagulation gland. With 3H E2, in contrast, epithelial nuclear labeling was high only in coagulation gland, moderate or low in seminal vesicle, low or absent in ventral and dorsal prostate and absent in ampullary gland and ampulla ductus deferentis. In the lamina propria of all organs nuclear labeling with 3H DHT was generally moderate and existed only in some cells, with the highest number in the ampulla ductus deferentis. With 3H E2, nuclear labeling in the lamina propria showed a high intensity in all organs, except in ventral and dorsal prostate which remained unlabeled. Many labeled cells were found in the deferent duct and its ampulla, while in the other organs only a few cells showed nuclear labeling with 3H E2. In the smooth muscle sheath of all organs, some muscle cells were moderately labeled with 3H DHT, but not with 3H E2. The results indicate the presence of nuclear receptors in male accessory sex organs for both dihydrotestosterone and estradiol. The differential patterns of 3H DHT and 3H E2 nuclear uptake suggest differential sensitivities of the individual organs and their tissue compartments for androgens and estrogens. PMID- 4030403 TI - Immunocytochemical demonstration of tubulin microheterogeneity within rat cortical and hippocampal pyramidal neurons. AB - Rat cortical and hippocampal pyramidal cells were immunocytochemically investigated using the TU-01 monoclonal antibody recognizing alpha-tubulin. The isotypic specificity of this antibody is distinct from that of other available alpha-tubulin antibodies; therefore, an intracellular heterogeneity among neuronal microtubules could be revealed by observing intensely immunostained apical dendritic microtubules in the complete absence of staining of the microtubules in the basal dendrites and perikarya of the same pyramidal cells. PMID- 4030404 TI - Cytochemical demonstration of adenylate cyclase activity with cerium. AB - Cerium was applied for the ultrastructural, cytochemical localization of adenylate cyclase (EC 4.6.1.1.). The enzyme activity was stimulated with norepinephrine, prenalterol and cholera toxin in the brown fat cells of newborn rats. The final reaction product was observed in the plasmalemmas of the stimulated adipocytes. The precipitate was finely crystalline, easily visible in the electron microscope and in the X-ray microprobe analysis it yielded cerium and phosphate peaks, respectively. The use of cerium offers a new tool valid for the cytochemical localization of adenylate cyclase enzyme related to the membrane receptors. PMID- 4030405 TI - Cationic dyes reveal proteoglycans on the surface of epithelial and endothelial kidney cells. AB - The glomerular epithelial cells of the rat kidney fixed by vascular perfusion with an aldehyde solution containing either safranine O or alcian blue (and 0.3 M MgCl2) display filaments which are located close to the outer surface of the plasma membrane. These filaments are similar to those revealed by the same methods in the laminae rarae of the glomerular basement membrane. Alcian blue (and MgCl2) further demonstrates the presence of anionic sites inside the endothelial cell pores of the glomerular and peritubular capillaries, on the luminal surface of endothelial cells of large renal vessels and along the basolateral surface of the epithelial cells of the Bowman capsule and of the proximal convoluted tubule. PMID- 4030406 TI - Cytochemical studies of acid phosphatases in the rat lateral prostate with special reference to secretory apparatus and lysosome system. AB - A cytochemical study of acid phosphatase (AcP-ase) in the lateral prostate of the rat was performed to investigate whether AcP-ase in the secretory apparatus can be distinguished from AcP-ase in lysosomes and their related structures. Two types of AcP-ase were observed in the rat lateral prostate. One was found in the secretory apparatus (Golgi saccules and some Golgi vesicles, condensing and secretory vacuoles), and reacted well with naphthol AS-BI phosphate (N AS-BI P) as substrate; the other was found in the lysosomes and Golgi-associated endoplasmic-reticulum-lysosome system (GERL)-like structure, and reacted well with beta-glycerophosphate (beta GP) as substrate. Although the AcP-ase which reacted well with N AS-BI P was also observed in certain portions of pleomorphic lysosomes, it was concluded that it was the same as the AcP-ase found in the condensing and secretory vacuoles, since a lysosome engulfing a condensing vacuole was often observed. Therefore, it is concluded that the AcP-ase in the secretory apparatus in the rat lateral prostate is different from the AcP-ase in lysosomes. Condensing vacuoles appear to originate from particular portions of Golgi saccules, but not from the GERL or GERL-like structure, at least in the rat lateral prostate. PMID- 4030407 TI - Simultaneous ultrastructural demonstration of retrogradely transported horseradish peroxidase and choline acetyltransferase immunoreactivity. AB - In order to study the synaptic connections of neurons identified by their projection target and neurotransmitter content, we have adapted a method of combining retrograde tracing of horseradish peroxidase (HRP) and immunocytochemistry at the electron microscopic level. HRP was injected into the rat amygdala. Sections from the rostral forebrain were processed according to the 3,3'-diaminobenzidine/glucose oxidase reaction followed by choline acetyltransferase (ChAT) localization. Neurons in the ventral pallidum which contained both the diffuse immunoperoxidase reaction product (ChAT) and large electron dense bodies characteristic of retrogradely transported HRP were defined as double labeled, i.e. cholinergic neurons that project to the amygdaloid body. PMID- 4030408 TI - Histochemical localization of hormone sensitive adenylate cyclase in defined nephron epithelia in culture. AB - Distal nephron epithelia of defined anatomical origin were microdissected from rabbit kidneys and individually explanted into an in vitro culture system. The 7 day monolayers grown from four different nephron epithelia were studied for the presence and amount of adenylate cyclase reaction product. In each case basal adenylate cyclase was compared with the enzyme reaction product after stimulation by arginine vasopressin, calcitonin, parathyroid hormone (PTH) and isoproterenol. In cortical collecting tubule cultures, the reaction was stimulated by vasopressin greater than isoproterenol greater than calcitonin. PTH had no effect. In cortical thick ascending loop of Henle cells, the stimulation was by calcitonin greater than vasopressin = PTH. Isoproterenol had no effect. In medullary ascending loop epithelia, stimulation was by vasopressin = calcitonin. Neither isoproterenol nor PTH had an effect. These observations indicate that adenylate cyclase is histochemically demonstrable in cultivated cells from rabbit distal nephron segments and that the enzyme activation by hormones is differential according to the epithelium of origin. PMID- 4030409 TI - [Peripheral vestibular neuropathy and a central vestibular equivalent]. AB - The results of the initial and follow-up examinations of 217 patients with vestibular neuritis and 63 patients with a so called "vestibular neuritis syndrome" were statistically evaluated and quantified using the vestibular index. The results for patients with vestibular neuritis were compared at the different stages to those of patients after neurectomy of the vestibular nerve. The site of the lesion in patients with vestibular neuritis may therefore be in the region of Scarpa's ganglion (retrolabyrinthine). Alternatively the total peripheral end organ may be affected. This conclusion agrees with histopathological findings. The "vestibular neuritis syndrome" included patients with the same history as patients with true vestibular neuritis but with signs of a central-vestibular disturbance or a combination of a central and peripheral lesion of the vestibular system. In these cases the lesion may be situated closer to the vestibular nuclei or its central pathways. Both disorders were similar with respect to history, etiology and the prognosis. PMID- 4030410 TI - [Comparison of different audiometric procedures for infants less than 1 year old]. AB - The comparison of all the hearing test methods that have been advocated during recent years shows that all have severe drawbacks and are thus unsuitable for screening for hearing loss in newborns. Therefore it is better to screen by the high risk registry. All high risk children must be seen by the paedaudiologist. PMID- 4030411 TI - [Evaluation of hearing improvement due to hearing aids]. AB - A method to assess the hearing improvement due to hearing aids is described. This method has been used routinely at a local hospital for 2 years on 200 patients. This method is based on the assessment of the speech reception threshold for sentences ("Marburger Satztest") in silence and in various noise levels (speech simulating noise). The following were used for the assessment of the hearing aid: the improvement of the speech reception threshold in silence with or without a hearing aid, the maximum tolerable noise level (i.e. the noise level at which everyday speech becomes subliminal for patients with hearing aids) and the noise level at which the speech reception threshold with the hearing aid is worse than without. PMID- 4030412 TI - [Status of the canal system in the temporal bone and its variations. II. Canals of the petrous portion between the internal acoustic meatus and the inferior surface of the petrous portion]. PMID- 4030413 TI - [Clinical aspects and therapy of lymphangiomas, hemangiomas and nevi in the area of the head and neck]. AB - The superficial angiomas and nevi arise from the endothelial cells, the pigment cell-system or the epidermal cells. Hemangiomas are benign tumours of the endothelial cells appearing predominantly in female newborn infants. Depending on localisation, growth and proliferation there is a tendency for spontaneous involution. For irreversible dysfunction or anatomical deformities surgical resection during the growth phase of the hemangioma is indicated. Surgery may be necessary to improve the functional and esthetic appearance after spontaneous involution causing loose residual skin. Radiotherapy of the lesion is rarely indicated. Systemic steroid therapy in cooperation with the pediatrician should be reserved only for desperate cases such as Kasabach-Merrit-Syndrome. Port wine nevi without scars can be covered with skin tanning cosmetics. Argon-Laser Therapy is not yet so selective that healing can be achieved with certainty and without scars. Clinical progression requires surgery, especially for racemose angiectasia. Arterial embolization should only be used under special conditions, and then only as pretreatment. Lymphangiomas are mostly angiectatic processes, especially of lymphatic vascular tissue and vessels. Even large cystic lymphangiomas can be treated quite well by surgery, but operations on large diffuse invasive lymphangiomas often cause lymphedema and infection similar to erysipelas leading to pseudorecurrence. The benign malformations of the pigment cell system require clear differentiation from malignant melanoma and its precursors. Malignant melanoma develops more frequently from congenital nevi of the deep type than from other pigmented lesions. Malignant melanomas arising from giant nevi are usually diagnosed too late so that almost all patients die. Removal of giant nevi as early as possible is recommended. The epidermal malformations, too, need accurate diagnosis. Multisymptomatic syndromes such as the Basal-Cell-Nevus-Syndrome, and vascular and pigment cell abnormalities require special care. PMID- 4030414 TI - [Infratemporal approach in nasopharyngeal cancer: operative technics and initial results]. AB - When nasopharyngeal cancer recurs after radiotherapy, and when the dura is not invaded, radical excision is still possible by means of the infratemporal fossa approach (ITFA), developed by the senior author. In an effort to improve the results of radiotherapy, 13 cases of residual or persistent disease were operated on by this approach between 1977 and 1981. Of seven patients with T4 tumours, all died of persistent disease within two to three years. Six patients with T1 or T2 non-keratinizing squamous cell carcinoma are alive two to five years after surgery. Only one patient needed additional surgery for another recurrence. The approach results in a complete conductive hearing loss and permanent anaesthesia of the mandibular nerve. The procedure is safe and well tolerated. Average hospital stay is 14 days. A combination of radiotherapy and surgery is recommended for T1 and T2 carcinoma in order to improve longterm survival rates. PMID- 4030415 TI - [Local differences in the tissue picture of chronic hyperplastic paranasal sinus mucosa]. AB - Five standardised mucosal biopsies were taken on each side during endoscopic sinus surgery from twenty-two patients with severe hyperplastic paranasal sinusitis. The different samples from the ethmoidal and maxillary sinus mucosa were compared with regard to the uniformity of histological changes. Each histological component of the sinus mucosa was involved to a different extent in local pathological changes. These analyses support the view that the character of the chronic inflammatory process is influenced by local pathogenetic factors. Preoperative biopsies do not give information about the general condition of the sinus mucosa. PMID- 4030416 TI - [Indications for surgical intervention in occult paranasal sinusitis in the child]. AB - Sinus surgery, including antroscopy, is rarely indicated in children because radiological changes and their histological correlates often disappear spontaneously. In this paper we report the follow up of 17 children who underwent sinuscopy for an occult sinusitis with radiologic opacity of the maxillary sinuses. Even though considerable inflammatory reactions were seen normal x-rays were found in 68% one year after endoscopy. PMID- 4030417 TI - [Rhinomanometric measurements in obstructed nasal respiration before and following rhinosurgical interventions]. AB - 355 patients with nasal obstruction caused by different disease were treated by various nasal operations. Active anterior rhinomanometry was performed before and after operation, both before and after decongestion of the nasal mucosa. 254 patients were reassessed 6 to 9 months later. On average an increase of nasal airway was achieved from V 1.5 = 0.46 1/s before operation to 0.74 1/s after operation (before decongestion) and from V 1.5 = 0.55 1/s before operation to 0.83 1/s after operation (after decongestion of the nasal mucosa). The decongestion effect and the differences between the better worse nasal cavities showed a significant decrease after operation. Rhinomanometric evaluation of the various nasal operations is presented for patients with nasal blockade caused by various diseases. PMID- 4030418 TI - [Format filling photodocumentation with the flexible endoscope Olympus ENF-P using a new objective combination]. AB - Photographic documentation is an important part of endoscopy. A flexible endoscope of small diameter, developed for special use in ENT is described. The resulting photographs fill the slide ("format filling"). This new objective combination fulfills the requirements of endoscopic construction and permits good photographic documentation of concealed parts of the ear, nose and throat which cannot be achieved by conventional rigid endoscopes. PMID- 4030419 TI - [Arteriovenous fistula of the temporal vessels--a rare complication of blunt cranial trauma]. AB - A very rare case of an arteriovenous fistula of the temporal vessels following a blunt trauma to the skull with fracture is reported. The symptoms, diagnosis, pathogenesis and operative treatment are discussed. PMID- 4030420 TI - A new HLA Bw16 subtype defined in both Negroid and Saudi Arabian populations. AB - Serological identification of a new HLA-Bw16 subtype, B39B, was made by the analysis of reaction patterns of many alloantisera and one monoclonal antibody. The B39B pattern of reactivity was shown to be distinct from HLA-Bw38, Bw39, and 8w57. Cytotoxicity testing before and after absorption suggests that the B39B specificity belongs to the HLA-B7 cross-reactive group. The B39B was clearly demonstrated in two families. This antigen was detected in Negroids and Saudi Arabian Caucasoids but not in a large panel of British Caucasoids. PMID- 4030421 TI - Trigger activation of the paradoxical salivatory response to atropine in the parasympathetically denervated human parotid gland. AB - The author describes a specific intermediate condition of the response to atropine during the 2nd stage of denervation of the human parotid gland. Of the entire cohort of 110 subjects, some 20 subjects have been observed systematically. They demonstrated an extremely intense atropine salivation that followed an additional trigger activation, namely food or acid irritation of the mouth mucosa. The initial phase of such a stimulation was characterized by a sharp, explosive increase in secretion. The following conclusions have been inferred: (1) in the 2nd stage of parasympathetic denervation of the human parotid gland, there emerges a specific intermediate condition of 'readiness' for an extremely intense paradoxical salivatory response to atropine and other cholinolytics; (2) the pre-start 'readiness' state may be activated by means of adding a trigger signal followed by an explosive occurrence of abundant secretion; (3) only food or acid irritation, even to a minimal extent, of the mouth cavity may serve a specific trigger signal; (4) a stable state of this trigger readiness has been observed in 20 subjects for years, while in other subjects it has been observed as a transitory event between the 1st and the 3rd stages of denervation and during the regression of symptoms in the rehabilitation period; (5) suggestions have been made concerning the trigger activation mechanism of the atropine salivatory paradox and the evolutionary, model and clinical significance of the events described. PMID- 4030422 TI - Napping behavior during "spontaneous internal desynchronization": sleep remains in synchrony with body temperature. AB - Patterns of sleep and wakefulness exhibited in an environment without time cues are generally considered to be monophasic, with a distinct relationship between sleep episodes and the minimum of body core temperature. In some cases this relationship between major sleep episodes and temperature becomes replaced by an apparently varying phase relationship between the two variables called "spontaneous internal desynchronization". In the present study the sleep-wake and temperature data of six subjects living in an environment without time cues and exhibiting internal desynchronization were reanalyzed to include subjectively designated naps. Two groups of naps were identified based on their phase positions relative to temperature, with one group occurring around the temperature minimum and another group clustering approximately halfway between successive minima. The results support the suggestion that neither monophasic sleep placement nor sleep patterns typically associated with spontaneous internal desynchronization reflect biological sleep tendency. Rather, sleep tendency is reflected more accurately by the bimodal sleep patterns exhibited by subjects who are allowed to time their sleep and waking with no restrictions. PMID- 4030423 TI - Temporal organization of behavior. PMID- 4030424 TI - Comments on time in action and perception. PMID- 4030425 TI - Schemas for the temporal organization of behaviour. AB - Those aspects of the timing of behaviour are emphasized which derive from the need for the organism to coordinate its actions with objects in the environment. Such coordination may require the serial performance of certain actions, yet permit elements of concurrency as well. Perceptual and motor schemas are introduced as units for the functional description of behaviour intermediate between a purely phenomenological description and an account of the detailed neural mechanisms of behaviour. The language of coordinated control programs is outlined to suggest how such schemas are orchestrated in visually and tactilely guided behaviour. Finally, a crucial property of the timing of many movements is discussed: their division into a fast (feedforward, ballistic) phase followed by a slow (feedback) phase. This division is analyzed in the light of the effect of brain damage on reaching movements. PMID- 4030426 TI - Temporal tracking and synchronization strategies. AB - Timing measures were obtained from subjects instructed to tap a Morse key in synchrony with a metronome which marked a timing pattern consisting of alternating blocks of intervals of imperceptibly different duration. "Synchronization strategies", which consisted of computer-simulated sets of rules, or algorithms, hypothesized to be the basis of synchronization behavior, were used to simulate tapping sequences in response to the same metronome sequences. The human and computer-simulated synchronization data were analyzed identically and compared to determine which of the postulated strategies could explain the observed human tapping behavior. The strategies generating timing data statistically indistinguishable from the human data involve a pattern of human-metronome interaction, and a corresponding transfer of information, more complex and subtle than previous investigations had implied. PMID- 4030427 TI - The percentage of projection neurons and interneurons in the human lateral geniculate nucleus. AB - Projection neurons and local circuit neurons of the human lateral geniculate nucleus (LGN) offer different patterns of lipofuscin pigmentation. One type of projection cell (type I neuron) and two varieties of local circuit neurons (type II and type III neurons) can be distinguished on account of their characteristic pigmentation. The majority of the nerve cells are type I projection neurons. Pigmented type II neurons comprise about 8.5% and type III neurons devoid of pigment amount to only 0.2% of the nerve cells. PMID- 4030428 TI - Human contrast sensitivity: regional retinal differences. AB - Contrast sensitivity functions of foveal and of perifoveal upper and lower hemiretinal regions were measured in a population of twenty subjects. Foveal stimuli yielded consistently higher contrast sensitivities as well as a shift of the maximal sensitivity towards higher spatial frequencies as compared to perifoveal stimuli. The upper hemiretinal area was more sensitive at all spatial frequencies tested than the corresponding lower hemiretinal area. The statistical comparisons were highly significant, indicating not only regional retinal differences in visual acuity as reflected by the different contrast threshold levels at the highest spatial frequency, but also global differences between the upper and lower hemiretina systems not restricted to certain spatial frequency channels. PMID- 4030429 TI - Tolerance of peripheral nerve to intraoperative radiotherapy (IORT): clinical and experimental studies. AB - In our clinical experience combining wide excision and intraoperative radiotherapy (IORT), five patients have developed clinical signs of lumbosacral or sciatic neuropathy within 9 months of receiving IORT to a dose of 20-25 Gy. Three patients showed recovery of nerve function over several months while two patients have shown no recovery and have near complete loss of extremity function. In an attempt to investigate this clinical observation further, the lumbosacral plexus and sciatic nerve of American foxhounds were surgically exposed and received a single dose of IORT ranging from 20-75 Gy. An approximate linear relationship between radiation dose and time to onset of hind limb paresis is found with 19 of 21 irradiated dogs showing clinical signs of nerve injury within an interval of 1-19 months. No recovery of nerve function is seen in these dogs. Histological study of the irradiated nerves demonstrates a loss of nerve fibers, particularly those of the large myelinated type without evidence of vascular occlusion or thrombosis. These studies suggest that peripheral nerve may be a dose-limiting normal tissue in clinical studies of IORT. PMID- 4030430 TI - Pretherapeutic flow cytometric DNA investigations in radiotherapy patients with maxillo-facial carcinomas. AB - In order to analyze the possible meaning of cellular DNA content and cell cycle phases for the radiosensitivity and the prognosis of human malignant tumors, flow cytometric measurements have been performed in biopsies of 131 patients with histologically proven squamous cell carcinomas of the maxillo-facial region. In two-thirds of the patients (88/131; 67%), aneuploid tumor cell lines have been found, only 33% (43/131) had a diploid DNA distribution pattern. The average DNA index (DI) of the aneuploid carcinomas was 3.4 +/- 0.6 (normal nonmalignant tissue DI = 2.0). The frequency of S-phase cells, which represents the "proliferative activity", was between 4.8 and 63.2%, regardless of the ploidy stages. The aneuploid carcinomas had about twice as many S-phase cells (mean 23.7 +/- 11.8%) than diploid tumors (mean 12.7 +/- 4.8%). Mean survival for patients with diploid carcinoma and aneuploid carcinoma was 12 and 9.5 months, respectively. Concerning the relationship of S-phase frequency and survival times in our material there was a high negative statistical correlation (Spearman-Rank test) in patients with diploid carcinomas. A high S-phase fraction resulted in short survival times. No correlation was found in the aneuploid carcinomas: patients with tumors in high S-phase values in their biopsies showed no difference in prognosis in comparison to tumors with lower S-phase fractions. PMID- 4030431 TI - Cell-cell matrix interactions in induced lung injury. II. X-irradiation mediated changes in specific basal laminar glycosaminoglycans. AB - The thoraces of male LAF1 mice were irradiated at doses of 5, 9, or 13 Gy. The animals were killed at times of 1 hr, 1 day, 1 wk, 4 wks, and 12 wks postirradiation (PI). The lungs were removed, enzymatically or detergent digested, fixed with ruthenium red for demonstration of anionic sites, and processed for electron microscopy. Untreated (0 Gy, 0 time) and sham irradiated control groups were also processed. Sections of lungs were examined and changes in alveolar basal laminar anionic sites were quantitated. Changes in three groups of glycosaminoglycans (GAGs) were identified: chondroitin 4 and 6 sulfate dermatan sulfate, hyaluronate, and other GAGs (principally heparan sulfate). At 1 hr PI, all groups showed a marked decrease in site number over controls, which continued to 1 wk. By 4 wks there was a marked relative increase in heparan sulfate containing sites for doses of 13 Gy and a moderate increase for the other doses. At 12 wks the level of heparan sulfate was considerably above normal for doses of 13 Gy and just above normal for the other doses. Chondroitin-dermatan sulfate had recovered by 12 wks for doses of 13 Gy, but was still subnormal for other doses; however, hyaluronate-containing sites recovered only slightly by 12 wks. The implications for this change on basal laminar permeability and the induction of fibrosis are discussed. PMID- 4030432 TI - Correlation of the dermal microvasculature morphology with the epidermal and the endothelial population changes produced by single X ray fractions of 1649, 2231 and 2619 rad in swine. AB - The role of the dermal microvasculature in the production of skin changes has not been specified. The healing moist reaction observed between 21 and 36 days following X ray exposures of 1649, 2231, and 2619 rad results from the loss and repopulation of the epidermal basal cells. The second breakdown occurring between 36 and 70 days results from the loss of endothelial cells in vessels of the papillary plexus. The epidermal population in swine skin decreases linearly to a nadir at 23 days and returns to control levels (and beyond) exponentially at 28 32 days. During this period, the endothelial cell density remains at control levels. At 28-36 days there is an abrupt decrease to 50% of control levels following administration of 1649 rad and a further decrease to 0 after 2231 and 2619 rad by 70 days. The qualitative morphology of the microvasculature remains unchanged until 32-36 days following irradiation. At that time there is increased endothelial cell pyknosis and loss of endothelial cells. A decrease in the vascular lumen cross-section profile density occurs by 43-49 days. This is accompanied by a progressive vascular dilatation. Interstitial edema becomes marked, with an inflammatory infiltrate of varying amount. Micro thrombi are found after 2619 rad, but are nearly absent after 1649 rad. PMID- 4030433 TI - pH distribution in human tumors. AB - The effectiveness of hyperthermia in tumor therapy may depend on a lower extracellular pH of tumor compared to that of normal tissue. A technique for measuring extracellular pH in human tumors has been devised to test the usefulness of this parameter as prognostic indicator of tumor hyperthermia response. In a preliminary study 50 of 53 pH readings from 14 human tumors (both heated and unheated) were below normal physiological pH. Tumor pH values ranged between 5.55-7.69 (average for unheated tumors 6.81 +/- 0.09, SEM, only one determination was above 7.40). Although there was considerable heterogeneity of pH within tumors, the accuracy and drift of the 21 gauge needle electrode were not a problem. Fifteen minutes were required for pH stabilization after insertion of an 18 gauge open-ended catheter, and less than 5 min for equilibration after electrode insertion into the catheter. A saline wheal was used for anesthesia to preclude modification of pH by anesthetics. Central portions of tumors were no more acidic than peripheral regions, but large tumors tended to be more acidic than small tumors. The pH of several tumors of various sizes and histologies was also determined immediately before subsequent treatment sessions. These measurements were made by reinsertion of catheters in approximately the same locations at each session. The trend appeared to be that pH increased with the number of treatment sessions. Measurements of pH were made in four patients immediately prior to and at the termination of a heating session (same locations since catheter remained in place during heating sessions). Three of the four tumors showed increased pH readings of 0.25-0.54 units during heating. However, none of the four tumors achieved temperatures exceeding 42 degrees C. The pH measurement technique developed provides a safe and relatively easy method for determining extracellular pH in human tumors. There appears to be a correlation of pH values with tumor size, treatment session, and possibly blood flow. PMID- 4030434 TI - Comparative theoretical performance for two types of regional hyperthermia systems. AB - Regional hyperthermia systems have drawn attention because of their potential for depositing power noninvasively in deep-seated tumors. Two such systems that have received clinical attention because of their ability to deposit significant amounts of power in tissue are magnetic induction devices and annular phased array applicators. In this paper, theoretical calculations for the specific absorption rate (SAR) and the resulting temperature distributions for these systems are compared. The finite element method is used in the formulation of both the electromagnetic and thermal boundary value problems. Six detailed patient models based on CT-scan data from the pelvic, visceral, and thoracic regions are generated to simulate a variety of tumor locations. In general, the annular phased array deposited more power within the tumor and produced better temperature distributions than the magnetic induction device. However, the ratio of the maximum power absorbed by the tumor to the maximum power absorbed in normal tissue does not appear to be high enough for either device to heat significant portions of perfused tumors to therapeutic temperatures under a wide range of physiological conditions. The results contained herein should aid the physician in comparative treatment planning with existing regional hyperthermia systems. PMID- 4030435 TI - Intraoperative interstitial microwave-induced hyperthermia and brachytherapy. AB - Intra-operative placement of 11-gauge nylon catheters into deep-seated unresectable tumors for interstitial brachytherapy permits localized heating of tumors (hyperthermia) using microwave (915 MHz) antennas which are inserted into these catheters. Four preliminary cases are described where epithelial tumors at various sites were implanted with an antenna array and heated for 1 hour, both before and after the iridium-192 brachytherapy. Temperatures were monitored in catheters required for the appropriate radiation dosimetry but not required for the interstitial microwave antenna array hyperthermia (IMAAH) system. Additional thermometry was obtained using nonperturbed fiberoptic thermometry probes inserted into the catheters' housing antennas. No significant complications, such as bleeding or infection, were observed. This approach to cancer therapy is shown to be feasible and it produces controlled, localized hyperthermia, with temperatures of 50 degrees C or more in tumors. This technique may offer a therapeutic option for pelvic, intra-abdominal and head and neck tumors. PMID- 4030436 TI - Is NSD-TDF useful to radiotherapy? PMID- 4030437 TI - Intrinsic radiosensitivity of human cell lines is correlated with radioresponsiveness of human tumors: analysis of 101 published survival curves. AB - One hundred and one published survival curves for 92 human cell lines (including 64 tumor lines) have been analyzed in terms of several parameters that are supposed to characterize cell radiosensitivity. Values for n, Do, alpha and beta (from the linear quadratic model), D (Mean Inactivation Dose), and survivals at 2 Gy and 8 Gy have been obtained for each curve. It was found that: I. the initial part of the survival curve is specific to the corresponding cell line; II. this initial part is well characterized by the parameters alpha and D, the values of which can be used to compare intrinsic radiosensitivity among human cell lines; III. human tumor cell line radiosensitivity (expressed in terms of alpha, D and survival at 2 Gy) reflects the clinical radioresponsiveness of the tumors from which the cell lines are derived. Thus, cells from tumors with low radioresponsiveness (melanomas and glioblastomas) are the less radiosensitive. Furthermore, the range of survival at a dose of 2 Gy is broad enough to account, in large measure, for observed differences in clinical tumor radioresponsiveness. PMID- 4030438 TI - Growth hormone producing pituitary adenomas with concomitant hypersecretion of prolactin are particularly sensitive to photon irradiation. AB - The effect of photon irradiation (50 Gy with a 3-field technique in fractionated doses) on growth hormone (GH), prolactin (PRL), and somatomedin A (SMA) was studied in 25 patients with acromegaly after previous unsuccessful surgery. In patients with concomitant hypersecretion of PRL, the GH reduction was 70 +/- 22% 1 year and 88 +/- 10% 3 years after radiotherapy. The corresponding reductions in patients with isolated GH hypersecretion were 42 +/- 25% and 60 +/- 22%. The reduction of GH levels was most notable the first year after radiotherapy in 16 patients and during the second year in 7 patients. Serum PRL decreased after radiotherapy in all patients with hyperprolactinemia, whereas PRL in normoprolactinemic patients showed inconsistent changes, including PRL increments in 8/12 patients. The effect of radiotherapy on GH and PRL was not correlated to the irradiation target volume or the cumulative radiation effect. SMA levels decreased after radiotherapy, but became normal only in 3 patients, all with pretreatment GH less than 5 micrograms/l. Radiotherapy, 3 years after treatment, appeared to be equivalent to the primary surgical intervention in reducing GH and SMA in patients with acromegaly due to advanced macroadenomas. Patients with concomitant hyperprolactinemia showed increased sensitivity to radiation compared to normoprolactinemic patients with acromegaly. PMID- 4030439 TI - Response of mouse tumor to interferon inducer and radiation. AB - The antitumor effect of interferon inducer poly(ICLC), given prior to the radiation treatment of Lewis lung carcinoma in C57Bl mice was studied. To induce the tumors, the mice were injected subcutaneously into the hind leg with 3 X 10(4) or 3 X 10(5) tumor cells. The combination treatment consisted of poly(ICLC) given at 1.25 mg/kg 6 hours before 400 cGy of 60Co gamma rays. All treatments were given three times over 1.5 weeks. The local response, as measured by the delay in the tumor growth, was significantly higher in the combination treatment group than in poly(ICLC) or local irradiation groups. Following the termination of treatment, tumor regrowth was observed. The survival of poly(ICLC) treated mice was influenced by the number of transplanted tumor cells. Thus, untreated mice which received 3 X 10(4) or 3 X 10(5) (2 or 20 TD50) of tumor cells had similar mean survival time of 25.4 +/- 1.9 and 22 +/- 84 days, respectively (p greater than 0.05). The mice, treated by a combination of poly(ICLC) and local irradiation survived 48.2 +/- 2.1 days and 30.7 +/- 1.2 days (p less than .01), with higher survival in 2 TD50 tumor cell groups. Thus, data obtained in this study in mice showed that administration of an interferon inducer poly(ICLC) prior to local irradiation can improve tumor response and survival. PMID- 4030440 TI - Routine quality control of Ir-192 sources: results of 46 months of surveillance. AB - Documented problems with loose and inert Ir-192 seeds in nylon ribbons prompted us to develop a quality control program. Several problem cases are illustrated. A sample of ribbons from each shipment is measured in a radioisotope dose calibrator. Results of the measurements over a 46-month period are presented. PMID- 4030441 TI - Comparative dosimetry between iridium wires and seed ribbons. AB - We have undertaken a computer study that explores the conditions under which seed ribbons may replace iridium 192 wires in the Paris System. Compared with continuous iridium 192 wires, seed ribbons demonstrate greater inhomogeneity and loss of flexibility, simplicity, and other advantages. Nonetheless, we have defined the conditions where seed ribbons may be used in the Paris System to give satisfactory dose distributions and acceptable levels of heterogeneity within any given implant volume. These conditions include seed length, spacing between seeds, number of seeds per ribbon, and geometric arrangement of ribbons. PMID- 4030442 TI - Management of squamous cell carcinoma of the anus and adenocarcinoma of the lower rectum. PMID- 4030443 TI - Lack of correlation between epidermal basal cell survival and probability of healing of skin reactions in swine. PMID- 4030444 TI - Low clonogenic fraction need not imply survival/healing correlation. PMID- 4030445 TI - Bronchoscopy guided simulation of a bronchial neoplasm. PMID- 4030446 TI - Acupuncture for fleabite allergic dermatitis. PMID- 4030447 TI - Statistics in veterinary research. PMID- 4030448 TI - Periosteal transection and stripping for treatment of angular limb deformities in foals: clinical observations. AB - Correction was attempted in 27 foals (41 limbs) with angular deformities at the carpal region (35 limbs), metatarsophalangeal region (5 limbs) and distal end of the tibia (1 limb) by hemicircumferential transection of the periosteum (HCTP) and periosteal stripping (PS). Successful outcome was determined by straight limbs and soundness, which was achieved in 81.5% of the cases, with 60% of the horses in performance training. Follow-up evaluation for all foals was completed at various times after physiologic closure of the physes. In none of the limbs was the deformity overcorrected. Owners of foals with carpal region deviations corrected by means of HCTP and PS were satisfied with the result. The cosmetic appearance of the surgical site was excellent. The HCTP and PS adequately corrected greater degrees of carpal region deformity and greater degrees of deformity in older foals than previously reported with this or other surgical techniques. PMID- 4030449 TI - Periosteal transection and stripping for treatment of angular limb deformities in foals: radiographic observations. AB - Radiographs of 23 foals (35 forelimbs) with carpal region angular limb deformities, which later were corrected by hemicircumferential transection of the periosteum and periosteal stripping, were evaluated as to geometric and morphologic abnormalities. Geometric evaluation included deviation angle and deviation pivot point. Morphologic abnormalities were categorized as: asymmetric width of the distal radial physis; asymmetric width of the distal radial epiphysis; carpal bone collapse or fracture; carpal bone hypoplasia; carpal bone displacement; and metacarpal bone displacement. Fifty-seven percent of limbs had radiographic lesions in the carpal joints and 20% had lesions in the metacarpus. Of all the limbs, 48% had carpal or metacarpal bone hypoplasia, 26% had carpal or metacarpal bone displacement, and 12% had carpal bone collapse or fragmentation. On long-term followup (5 months to 2 years), 83% of the foals were sound and had straight limbs, regardless of the deviation angle, deviation pivot point, or morphologic carpal bone changes. Sixty percent of the foals were in performance training. About 50% of these foals in performance training had carpal bone hypoplasia before correction of the deviation. It was concluded that geometric and morphologic radiographic interpretation should be performed before surgical correction of carpal angular limb deformities with hemicircumferential transection of the periosteum and periosteal stripping, but that epiphyseal, carpal bone, or metacarpal bone changes, severe deviation angle (20 to 29 degrees) or distal location of the pivot point should not discourage attempted surgical correction. PMID- 4030450 TI - Giardiasis in a cattery. AB - Giardia sp infection was believed responsible for chronic, intermittent diarrhea in a group of 14 Persian cats. Seven of the cats were shedding Giardia sp cysts, and 6 of these cats had diarrhea at the time of fecal examination. Conversely, only 1 of 6 clinically normal cats in the group was shedding Giardia sp cysts. Cysts were not detected in feces of 2 cats with diarrhea. Cats less than or equal to 3 years old were more likely to be found shedding cysts. The parasite apparently was eradicated from the cattery by a combination of cage disinfection (1% sodium hypochlorite solution) and oral furazolidone treatment (4 mg/kg of body weight, BID for 5 consecutive days). During treatment, clinical signs resolved, and all cats remained clinically normal 2 months after treatment. PMID- 4030451 TI - Duodenal aspiration via flexible endoscope for diagnosis of giardiasis in a dog. AB - A 1-year-old male Pointer was admitted for evaluation of chronic diarrhea and mild weight loss. An aspirate of duodenal contents was obtained after infusing 0.9% Na Cl through a flexible endoscope passed into the proximal portion of the duodenum. Examination of the aspirated duodenal contents revealed a Giardia trophozoite, and the dog improved with metronidazole therapy. Duodenal aspiration via a flexible endoscope offers a new diagnostic technique for giardiasis. PMID- 4030452 TI - Giardiasis in a horse. AB - Giardia infection was believed responsible for chronic diarrhea, weight loss, lethargy, inappetence, and dermatitis in a 4-year-old Thoroughbred horse. Fecal cysts were detected by the zinc sulfate centrifugal flotation method. All clinical signs resolved upon treatment with metronidazole suspension (5 mg/kg body weight per os, TID for 10 days). PMID- 4030453 TI - Arterial thrombosis as the cause of lameness in a foal. AB - A 3-day-old foal was examined because of forelimb lameness. Brachial artery occlusion was diagnosed. The foal was euthanatized. Necropsy revealed brachial artery thrombosis and an atrial septal defect. PMID- 4030454 TI - Metastasis of bile ductule carcinoma in a cow. AB - An 8-year-old Holstein cow was referred with a history of weight loss, poor milk production, and hyperfibrinoginemia. Laboratory evaluation showed high gamma glutamyltransferase activity, prolonged sulfobromophthalein clearance half-time, and prolonged prothrombin and partial thromboplastin times. Multiple firm nodules with histologic evidence of bile ductule carcinoma were found on exploratory laparotomy and liver biopsy. Pulmonary and lymph node tumor metastases were extensive. Tumor development in this case could not be associated with any of the known contributing factors in ruminants. This case demonstrates the extensive metastatic potential of this tumor and nonspecific signs with which bovine hepatic disease can be manifested. PMID- 4030455 TI - Arsenic toxicosis and suspected chromium toxicosis in a herd of cattle. AB - Arsenic toxicosis and suspected chromium toxicosis were diagnosed in a herd of cattle that ingested ashes from lumber treated with copper, chromium, and arsenic. Findings included peracute death, depression, ataxia, weakness, recumbency, and watery diarrhea. Chemical analyses of liver, kidney, abomasal contents, rumen contents, and ashes revealed high concentrations of arsenic and chromium. Histologically, specimens of abomasum and duodenum had diffuse mucosal degeneration and engorged capillaries. Epithelial cells of the proximal convoluted tubules and distal collecting tubules of the kidney were swollen and had mild granular cytoplasmic degeneration. Burning lumber treated with copper, chromium, and arsenic does not remove the heavy metals from them, and ingestion of the ashes from the wood constitutes a hazard to livestock health. PMID- 4030457 TI - A simple and efficient system for filing professional and personal reference material. PMID- 4030456 TI - Some subtleties in horse insurance. PMID- 4030458 TI - Circumcostal gastropexy for preventing recurrence of gastric dilatation-volvulus in the dog: an evaluation of 30 cases. AB - Follow-up evaluation (mean, 13.7 months) was obtained in 30 dogs with gastric dilatation-volvulus that were surgically treated with circumcostal gastropexy. Evaluation was performed by questionnaire (29 dogs), radiographic contrast studies (23 dogs), and necropsy (6 dogs). The gastropexy was thought to be intact in all 23 dogs examined radiographically. Necropsy of 6 dogs dying from causes unrelated to gastric dilatation-volvulus (mean of 12.7 months after surgery) revealed an intact gastropexy site in each dog. Only 1 (3.3%) dog had clinical recurrence of gastric dilatation after surgery. Five additional dogs dying postoperatively were necropsied and had intact gastropexy sites. PMID- 4030459 TI - Cecal perforation in the horse. AB - The case records of 23 horses with cecal perforation (CP) were reviewed. The horses averaged 4.5 years of age (6 weeks to 13 years) and included 9 intact males, 12 mares, and 2 geldings. Twelve of the horses were Standardbreds, 9 were Thoroughbreds, and 1 each, a Belgian and Morgan. The horses were allotted to 2 groups: group I-13 hospitalized horses in which CP occurred unexpectedly, and group II-10 horses with CP at the time of admission. The horses characteristically had been sick or affected with disease unrelated to the cecum. Sixteen horses had been given nonsteroidal anti-inflammatory drugs before the onset of CP. Twelve of the 13 hospitalized patients (group I) had vague, scarcely recognizable clinical signs of gastrointestinal disease before CP. The clinical signs and clinical laboratory changes that appeared in affected horses were identifiable with severe endotoxin shock, secondary to peritoneal contamination with ingesta and bacteria. All horses died. At necropsy of the horses, the cecum was large and firm and was filled with ingesta, and the colon was empty; however, in 1 postpartum mare, the cecum and colon contained the usual amount of ingesta and were normal in size. In all horses, a single perforation was present, which appeared at various sites. The most common was a transverse perforation along the ventral aspect of the cecal body. Gross and microscopic examinations uncovered no existing disease near the perforation site or in other areas of the cecal wall or cecocolic orifice.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4030460 TI - Anthelmintic efficacy of febantel combined with praziquantel in dogs. AB - Ninety-four dogs were randomly assigned to 1 of 6 groups (5 treated and 1 untreated control) for evaluation of anthelmintic efficacy. Three anthelmintic formulations were studied: a febantel paste, a praziquantel paste, and a combination paste containing both active ingredients. Treated dogs were dosed once daily for 3 days. The minimal effective dosages in combination were established as 10 mg of febantel and 1 mg of praziquantel/kg of body weight. At those dosages for the combination, 99.5% to 100% of the major nematodes and cestodes identified (ie, Ancylostoma caninum, Trichuris vulpis, Toxocara canis, Dipylidium caninum, and Taenia pisiformis) were eliminated. Febantel paste (10 mg/kg) alone was ineffective against cestodes (14.2% elimination of Dipylidium caninum) and praziquantel paste (1 mg/kg) alone was ineffective (0% to 2.4% elimination) against nematodes. PMID- 4030461 TI - Salmonella shed by horses with colic. AB - Salmonella was isolated from 13 of 100 colicky horses admitted to a referral hospital. Seven horses were shedding the microorganism at or soon after hospital admission. A unique serotype was introduced into the hospital by a horse not shedding Salmonella at admission. It was concluded that 8 horses were infected before admission. Whether the remaining 5 horses were infected before or after admission could not be determined. Salmonella senftenberg was the most commonly isolated serotype from colicky horses and from horses with salmonellosis that were not colicky on hospital admission during the survey period. This organism was rarely isolated at the hospital before initiation of this survey. PMID- 4030462 TI - Acute hemodynamic effects of hydralazine in dogs with chronic mitral regurgitation. AB - The hemodynamic response to hydralazine administration was evaluated in 6 conscious small dogs with chronic mitral regurgitation. All dogs underwent invasive and noninvasive hemodynamic monitoring before and after hydralazine administration. Cardiac output and pulmonary capillary wedge pressure were measured with a Swan-Ganz thermodilution catheter. Systemic arterial blood pressure (AP) was measured directly by inserting a needle into the femoral artery. Standard M-mode echocardiograms and thoracic radiographs were obtained. Other hemodynamic variables were calculated. Base-line hemodynamic variables were altered severely in all dogs. Hydralazine decreased mean arterial blood pressure from 104 +/- 18 (mean +/- SD) to 78 +/- 12 mm of Hg (P less than 0.005), total systemic resistance index from 2,946 +/- 625 to 1,261 +/- 420 dynes-s-cm-5m2 (P less than 0.005), and pulmonary capillary wedge pressure from 40 +/- 5 to 26 +/- 3 mm of Hg, (P less than 0.005). Cardiac index increased from 2.92 +/- 0.72 to 5.36 +/- 1.67 L/min/m2 of body surface area (P less than 0.005). Mixed venous oxygen tension (PvO2) increased from 28.4 +/- 4.3 to 41.2 +/- 5.2 mm of Hg (P less than 0.001). Pulmonary edema resolved, as determined on thoracic radiographs. Mixed venous oxygen tension correlated well with the cardiac index (r = 0.92; P less than 0.001). It was concluded that hydralazine administration caused a small decrease in end diastolic diameter (4.8 +/- 0.9 to 4.5 +/- 0.8 cm, P less than 0.05) and end systolic diameter (2.6 +/- 0.8 to 2.3 +/- 0.7 cm, P less than 0.05). Fractional shortening and heart rate did not change.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4030463 TI - Type I biplanar configuration of external skeletal fixation: application technique in nine dogs and one cat. AB - Mechanical attributes and techniques of applying the type I biplanar (quadrilateral) configuration of external skeletal fixation are reported. The apparatus was used clinically on 9 dogs and 1 cat with long bone fractures. Bony union occurred in these animals, but was slightly delayed in one. Return to clinical function of the limb generally was good to excellent. The instances of delayed union and poor clinical results are discussed to emphasize the use of good techniques of application and case selection. PMID- 4030464 TI - Upper respiratory tract obstruction caused by a pharyngeal abscess in a filly. AB - A 3-year-old Thoroughbred filly had a pharyngeal abscess causing obstruction of the upper respiratory tract. Diagnosis was made by a combination of endoscopy, biopsy, cytology, and radiography. Treatment with antimicrobials and analgesics resulted in successful resolution of the abscess. PMID- 4030466 TI - Nonsurgical removal of a catheter embolus from the heart of a dog. AB - A fragment of an 18-gauge catheter was inadvertently severed during catheterization of the cephalic vein in a 7-year-old Golden Retriever. Under fluoroscopic guidance, the fragment was retrieved successfully from the right ventricle, using a self-constructed, loop-snare catheter. PMID- 4030465 TI - Pleural effusion secondary to metastasis of an ovarian adenocarcinoma in a horse. AB - An 11-year-old Quarter Horse mare was presented with ventral edema and pleural effusion, secondary to a disseminated ovarian adenocarcinoma. Bilateral thoracocentesis yielded 30 L of thin, blood-tinged fluid, which was a modified transudate. Cytologic examination of the fluid revealed large atypical cells, suggestive of carcinomatous neoplasia. Similar cells were found in the peritoneal fluid. The mare was euthanatized. Necropsy revealed a 35-cm diameter mass in the cranial mediastinum, ventral to the trachea. The left ovary was 25 cm in diameter and most of the parenchyma was replaced by red or brown friable tissue, containing numerous 1-to 3-mm cysts. Papillary adenocarcinoma of the ovary was diagnosed, based on the appearance and arrangement of tumor cells in the ovary, sublumbar and tracheobronchial lymph nodes, and mediastinal mass. Ovarian neoplasia should be considered in the differential diagnosis of pleural effusion in the horse. PMID- 4030467 TI - Non-dexamethasone-suppressible, pituitary-dependent hyperadrenocorticism in a dog. AB - A 5-year-old female dog with hyperadrenocorticism was determined to have pituitary-dependent hyperadrenocorticism even though plasma cortisol concentrations were not suppressed after high-dosage dexamethasone administration. The diagnosis was based on a supranormal response of plasma cortisol to ACTH administration and a lack of suppression of plasma cortisol concentration after administration of 0.1 mg of dexamethasone/kg. Although a higher dosage of dexamethasone (1 mg/kg) did not cause suppression of plasma cortisol, plasma ACTH concentrations in the dog were increased above those in clinically normal dogs, supporting a diagnosis of pituitary-dependent hyperadrenocorticism. During treatment with mitotane, the dog became unconscious and died. Necropsy revealed a pituitary tumor that had compressed and displaced the hypothalamus. Although high-dosage dexamethasone suppression tests often are useful in the differential diagnosis of hyperadrenocorticism, a lack of suppression of plasma cortisol does not necessarily exclude pituitary-dependent hyperadrenocorticism. PMID- 4030468 TI - 122d annual meeting of the American Veterinary Medical Association. Las Vegas, Nevada, July 21-25, 1985. Abstracts of scientific papers and poster presentations. PMID- 4030469 TI - Synopsis of US veterinary medical manpower study: demand and supply from 1980 to 2000. PMID- 4030470 TI - Antimicrobial susceptibility testing and antimicrobial drug dosage. PMID- 4030471 TI - Fibular head transposition for repair of cruciate-deficient stifle in the dog. AB - Fibular head transposition (FHT) was introduced as a surgical technique to reconstruct the cruciate-deficient stifle in the dog. Surgically moving the fibular head into a cranial position alters the orientation of the lateral collateral ligament, thereby preventing cranial drawer motion and minimizing internal rotation of the tibia. The technique was found to be safe, mechanically sound, and clinically effective. Comparison of clinical results for this technique with those for the fascial strip technique (using a uniform grading system) demonstrated an overall superior performance of FHT. Factors found to adversely influence clinical results were heavy body weight and meniscal damage. The interval between stifle injury and reconstructive surgery or the presence of associated osteoarthritic disease bore no relationship to clinical outcome. It was concluded that the clinical performance after FHT was equal or superior to other surgical methods for reconstructing the cruciate-deficient stifle in the dog. PMID- 4030472 TI - Urinary tract infection due to indwelling bladder catheters in dogs and cats. AB - Urine samples were collected from 27 dogs and 4 cats with indwelling urinary catheters connected to a closed system. Twenty-one animals had sterile urine at the initiation of catheterization. Eleven of these 21 animals developed positive urine culture after 4 (mean) days (range 1 to 10 days) of catheterization. Infections persisted after catheter removal in 6 of 8 animals. The 10 animals that did not develop bacteriuria had a shorter duration of catheterization (3 days vs 12 days, mean). Antibiotics (chloramphenicol, trimethoprim/sulfonamide, cephradine, lincomycin, gentamicin, or ampicillin) were used during the period of catheterization in 17 of 21 animals, 8 of which developed bacteriuria and 9 of which did not. Ten animals had bacteriuria at the initiation of urine collection for culture. The type of bacteria changed during the catheterization period in 6 animals, all of which were given antibiotics. Bacteria isolated from animals given antibiotics seemed to become increasingly antibiotic-resistant. PMID- 4030473 TI - Resistance of cerclage to knot failure. AB - The comparative ability of loop-knotted and twist-knotted cerclage to withstand tensile forces was tested. Two twist-knot devices and one loop-knot device were used to apply cerclage wires to a 5-cm diameter split circular jaw mounted on a tensile testing machine. Twist-knot devices were tested with 0.8-, 1.0-, or 1.2 mm wire, and the loop-knot device was tested with 0.8-, 1.0-, or 1.25-mm wire. For all wire sizes, the twisted knot provided greater resistance to knot failure than did the loop-knot. Of the 2 twist-knot devices, the Rhinelander wire tightener-twister produced the greatest resistance to knot failure. Knot resistance increased with increase in wire size for all devices tested. PMID- 4030474 TI - Electrodiagnostic evaluation of deafness in two English setter littermates. AB - Two English Setter littermates (male and female) were evaluated for hearing difficulties at 4, 16, and 24 months of age. Auditory function was evaluated by behavioral response to pure-tone sounds, tympanometry, brain stem auditory evoked response, and acoustic reflex testing. Hereditary sensorineural deafness was diagnosed in both dogs. The extent of the hearing deficit, as characterized by these tests, was slightly different between the dogs, as well as between the ears in 1 dog. PMID- 4030475 TI - Efficacy of ipronidazole against trichomoniasis in beef bulls. AB - Preputial smegma samples from 195 beef bulls were collected repeatedly and cultured for Tritrichomonas foetus. Seventy-five (38.5%) of these bulls were positive for trichomonads on at least 1 culture. Sensitivity of the culture procedure (number of positive cultures/number of total cultures from known positive bulls) was 81.6%. Storage of preputial smegma in lactated Ringer's solution at 5 C for 24 hours resulted in a 14% loss of sensitivity. Seventy-three of the 75 infected bulls were available for treatment and were alloted randomly to 2 groups. Bulls in both groups were treated with procaine penicillin (7,000 IU/kg, IM) for 2 days before ipronidazole treatment. Thirty grams of ipronidazole powder was dissolved in 60 ml of sterile water, and was given IM to group 1 bulls. Group 2 bulls were given a similar 30-g ipronidazole solution IM on day 1, and were given 15 g of ipronidazole dissolved in 30 ml of sterile water on days 2 and 3. Efficacy of treatment (ie, negative cultures of preputial smegma for trichomonads for 6 consecutive weeks after treatment) was 92.8% for the 42 bulls treated once and 100% for the 31 bulls treated 3 times. PMID- 4030476 TI - Uveitis associated with poliosis and vitiligo in six dogs. AB - Idiopathic panuveitis with retinal detachment was associated with facial poliosis, vitiligo, and alopecia in 6 dogs; 4 were adult males. Dermatohistologic examination of affected facial sites from all dogs revealed a lichenoid dermatitis and unusual histiocytic cells. Intensive topical and systemic corticosteroid and topical mydriatic/cycloplegic therapy was successful in controlling uveitis in all dogs for variable periods. Three dogs, monitored for 12, 30, and 46 months, retained useful vision despite infrequent recurrence of uveitis. One dog was lost for subsequent examination. Two dogs were euthanatized and necropsied. Ocular histologic examination of these dogs revealed extensive granulomatous iridocyclitis and choroiditis, with retinal detachment and lenticular degeneration. PMID- 4030477 TI - Myotonia in a chow chow. AB - Congenital myotonia was diagnosed in an inbred Chow Chow pup with severe muscle stiffness that regressed with exercise. Voluntary movement, percussion, or needle insertion caused sustained contraction of the muscles involved. Electromyographic recordings from several muscles contained myotonic discharges. Creatine kinase activity was mildly increased. Slight myofiber hypertrophy and a few atrophic fibers were seen in muscle biopsy specimens. Treatment of the pup with procainamide caused a marked decrease in clinical signs. Myotonia congenita in the Chow Chow appears to be inherited as an autosomal recessive trait. This condition can be diagnosed on the basis of clinical signs. Satisfactory clinical management of myotonia congenita can be achieved with procainamide. PMID- 4030478 TI - Amikacin therapy for Pseudomonas cellulitis in an Amazon parrot. AB - Amikacin sulfate, an aminoglycoside antibiotic, was used successfully to treat a case of severe Pseudomonas cellulitus in an Amazon parrot. Side effects of polyuria and polydipsia occurred, but resolved without treatment 3 weeks after the antibiotic regimen. Amikacin sulfate was given at a dosage of 0.04 mg/g of body weight, IM, twice a day, based on antimicrobial sensitivity results. Amikacin sulfate is indicated for P aeruginosa cellulitis that is resistant to gentamicin sulfate. Although it is potentially nephrotoxic, it can be used successfully in birds without permanent clinically evident renal effects. PMID- 4030479 TI - Tracheal collapse in two cats. AB - Two cats examined bronchoscopically to discover the cause of tracheal collapse were found to have tracheal obstruction cranial to the collapse. Cats with this unusual sign should be examined bronchoscopically to ascertain whether there is an obstruction, as the cause in these 2 cats was distinct from the diffuse airway abnormality that causes tracheal collapse in dogs. PMID- 4030480 TI - An analysis of semiflexible, closed-loop anterior chamber intraocular lenses. AB - We present the pathologic and scanning electron microscopic findings from 44 semiflexible, all polymethylmethacrylate, anterior chamber intraocular lenses (IOLs). These IOLs, which have round, small diameter, closed loops were removed following a variety of complications, including uveitis and/or the uveitis glaucoma-hyphema syndrome, secondary glaucoma, pseudophakic bullous keratopathy, cystoid macular edema, erosion into uveal tissue (with and without oval pupil), and iris neovascularization. Over 200,000 of these lens styles have been implanted. Even though the number of these IOLs accessioned in our laboratory is small, we feel this analysis documents some of the problems that may be encountered with this IOL design. Many of the complications documented in our series resulted in severe visual loss. In addition to tissue damage that appeared secondary to the mechanical tissue-to-implant interface, other causes of complications included variations in surgical technique, implantation into eyes with preexisting disease (including eyes that had undergone previous surgery), and damage to tissue that occurred during IOL removal. PMID- 4030481 TI - Determining intraocular lens power within the eye. AB - A method is described for determining the power of an intraocular lens (IOL) within the eye by measuring the horizontal dimension of the corneal reflected image (Purkinje-Sanson I) and the anterior IOL reflected image (Purkinje-Sanson III) as seen through a standard slitlamp with a target positioned 68 mm anterior to the focal plane of the biomicroscope. The horizontal K-reading (at 180 degrees) and the anterior chamber depth are the two other parameters necessary to calculate the exact power of the IOL. Seven tables that use these four measurements have been provided, eliminating the need for complex calculations. To determine the accuracy of this technique, ten implanted IOLs ranging from 9 diopters (D) to 27 D were chosen and their powers calculated; these calculated values were then compared to the actual IOL powers. The largest error was 0.5 D and the average error was 0.17 D. PMID- 4030482 TI - Alterations in the blood-aqueous barrier of the rabbit eye after neodymium: YAG photodisruption. AB - We studied the effects of the Nd:YAG laser on the blood-aqueous barrier following photodisruption of the anterior capsule, posterior capsule, and mid-vitreous of the albino rabbit eye with fluorophotometric techniques using albumin-bound fluorescein. After photo-disruption of the anterior capsule, fluorescence appeared in the anterior chamber at 30 minutes, peaked at two hours, and decreased almost to baseline values by 24 hours. No fluorescence was noted at any time in contralateral control eyes or in eyes receiving photo-disruption of the posterior capsule or mid-vitreous. PMID- 4030483 TI - Efficacy of laser interferometry in predicting visual result of YAG laser posterior capsulotomy. AB - One hundred fifteen patients with cloudy posterior capsules that required capsulotomies were evaluated by laser interferometry. The predicted acuity was within one line of postoperative acuity in 44 patients (38.3%) and within two lines in 73 patients (63.5%). The correlation coefficient between the predicted and actual post-capsulotomy acuities was 0.38. However, the predicted retinal visual acuity was compared to postoperative Snellen visual acuity and found to differ by an average of three lines. A large number of false negative results reduced the clinical usefulness of the test. PMID- 4030484 TI - Neodymium: YAG laser for anterior capsulotomy. AB - A technique using the Meditec OPL-3 YAG laser for anterior capsulotomy just prior to planned extracapsular cataract surgery is presented. A review of 1,108 cases showed this technique to have a low complication rate. Compared to conventional anterior capsulotomies, it is the author's opinion that this method gives increased operative control, shortens time in the operating room, and is a help with in-the-bag intraocular lens placement. PMID- 4030485 TI - Intraocular lens implant exchanges. AB - We reviewed 23 consecutive cases of intraocular lens implant exchange. Lens dislocation (26%) and chronic intraocular inflammation (26%) were the most frequent indications for lens exchange. Post-exchange vision was best in those eyes treated for inappropriate implant power (100% less than or equal to 20/40), intermediate in dislocation cases (83% less than or equal to 20/40), and poorest in eyes with chronic intraocular inflammation (50% less than or equal to 20/40), even though the inflammation usually improved. Eighty-three percent of the total cases remained within one line of the pre-exchange visual acuity. PMID- 4030486 TI - Factors affecting pseudophakic cystoid mascular edema: five randomized trials. AB - We summarize the findings of five randomized prospective, controlled studies that evaluated the following factors associated with the development of cystoid macular edema (CME) following cataract surgery: ultraviolet (UV) light from the operating microscope; postoperative UV light exposure; primary capsulotomy; retrobulbar hyaluronidase; and prostaglandin synthesis in the eye. The following were the major findings: (1) The presence of a UV-light filter on the operating microscope during cataract surgery made no statistically significant difference in the early postoperative (two to six months) angiographic incidence of CME or the visual outcome. (2) A UV-filtering posterior chamber intraocular lens (IOL) resulted in a statistically significant decrease in the early postoperative incidence of angiographic CME in postcataract-surgery patients but did not affect visual acuity. (3) Patients receiving primary capsulotomy during extracapsular cataract surgery showed a statistically significant higher incidence of early postoperative angiographic CME than did patients with an intact posterior capsule. Again there was no difference in visual acuity. (4) The addition of hyaluronidase to the retrobulbar anesthetic injection made no significant difference in the CME rate or postoperative visual results of patients undergoing extracapsular cataract surgery. (5) Patients undergoing IOL implant surgery who received topical indomethacin before surgery and for nine months postoperatively to inhibit prostaglandin synthesis in the eye showed a statistically significant lower incidence of early postoperative angiographic CME than did placebo-treated patients, but there was no significant difference between the two groups in postoperative visual acuity. PMID- 4030487 TI - Ultraviolet-absorbing intraocular lenses. PMID- 4030488 TI - Postimplantation bleeding after aspirin ingestion. PMID- 4030489 TI - Recent trends in anterior chamber implant technology. PMID- 4030490 TI - Use of pilocarpine intraocularly. PMID- 4030491 TI - Scanning electron microscopy of an irrigation/aspiration tip following a posterior capsular rupture. AB - The first use of a new irrigation/aspiration tip resulted in a posterior capsular rupture. Scanning electron microscopy of the tip revealed burrs on the aspiration portion of the tip, as well as poor finishing around the irrigation ports. PMID- 4030492 TI - Photo demonstration of quality of vision with intact posterior capsule. AB - The patient presented in this paper had a clinically clear but optically disturbing posterior capsule. The patient was able to visualize transparent refractive anomalies in the posterior capsule and the fine structure of a cataractous lens. PMID- 4030493 TI - New techniques of viscosurgery with phacoemulsification. AB - Sodium hyaluronate is a valuable aid for phacoemulsification and intraocular lens insertion. Procedures such as anterior capsulotomy, polishing the capsule, lens adjustment, incision closure, and conversion to planned extracapsular cataract extraction are facilitated when sodium hyaluronate is used. A new method of removing it from the eye is presented. PMID- 4030494 TI - Cortex removal system for manual extracapsular cataract extraction. AB - An irrigation/aspiration (I/A) system for cortex removal has been developed. It consists of an I/A cannula, connecting silicone tube, a handle with an aspiration cut-off device for the silicone tube, and an aspirating device. The aspirating pressure is produced by a fixed syringe, the cylinder of which is pulled by a weight. In addition, the aspirating system can be equipped with a small battery operated pump. The aspiration cut-off device located in the handle enables aspiration with one hand so the other hand is free for another instrument. Flushing back, if necessary, is possible. PMID- 4030495 TI - Symposium: Concepts of the self--the self or the Self? PMID- 4030496 TI - Intracellular pathways of endocytosed tracers in Leydig cells of the rat. AB - The endocytic activity of Leydig cells was examined by electron microscopy following the injection, into the interstitial space, of tracers used to examine fluid-phase endocytosis, ie, native ferritin and horseradish peroxidase-colloidal gold (horseradish peroxidase-gold), and adsorptive endocytosis, ie, cationic ferritin. At 5 minutes after injection, native ferritin or horseradish peroxidase gold was present in the interstitial space and free in the lumen of large endocytic vesicles forming at the cell surface. At 15 minutes, these tracers appeared in the matrix of pale multivesicular bodies, while at 30 minutes and 1 hour, the matrix of dense multivesicular bodies became labeled. Beginning at 1 hour, dense membrane-delimited bodies identified cytochemically as lysosomes were labeled. In the case of cationic ferritin, two distinct pathways were taken. In one pathway, cationic ferritin was observed 5 minutes after injection bound to the plasma membrane of Leydig cells and to the membrane of small and large endocytic vesicles. At subsequent time intervals, cationic ferritin appeared consecutively in pale, dense multivesicular bodies and lysosomes. In a second pathway, cationic ferritin was observed at 5, 15, and 30 minutes bound to the membrane of vesicles of intermediate size seen near the cell surface. At 1, 1 1/2 and 2 hours, cationic ferritin-containing intermediate vesicles appeared in increasing number in the Golgi region. However, cationic ferritin was never observed in the Golgi saccules themselves. At later time intervals (3-6 hours), intermediate vesicles labeled with cationic ferritin progressively disappeared from the Golgi region and the cell. Thus in Leydig cells, while fluid-phase tracers reached lysosomes exclusively, cationic ferritin, a tracer of adsorptive endocytosis, not only reached the lysosomes, but was also carried by the intermediate vesicles to the Golgi region of the cell. PMID- 4030497 TI - The origin of some acid hydrolases of the fluid of the rat cauda epididymidis. AB - The activity of N-acetyl-beta-D-glucosaminidase (NAG, 60.1 units/mg protein) and of acid phosphatase (57.7 units/mg protein) in fluid from the cauda epididymidis formed without any contribution from the testis (fluid obtained from a perfused and isolated cauda epididymidis or from an epididymis whose corresponding efferent ducts had been ligated for 40 days) was significantly higher than the activity of these enzymes in normal fluid (39.6 and 41.2 units/mg protein, respectively). Arylsulphatase activity of the locally formed fluid (11.2 units/mg protein) was lower than that of normal fluid (74.1 units/mg protein). The rete testis fluid was relatively rich in arylsulphatase since the ratio of arylsulphatase to acid phosphatase activity was 17 times higher in this fluid than in locally formed fluid. It is concluded that the activities of NAG and acid phosphatase in normal fluid from the epididymis originate in the epididymal tissue, while most of the arylsulphatase activity comes from the testis. PMID- 4030498 TI - New antitumor antibiotics, FR-900405 and FR-900406. I. Taxonomy of the producing strain. AB - An actinomycete which was isolated from a soil sample produces new antitumor substances. The morphological and cultural characteristics of the strain resemble those of the genera Streptomyces Waksman and Henrici 1943 and Actinomadura Lechevalier and Lechevalier 1970. Cell wall composition analysis showed that strain No. 6049 contained meso-2,6-diaminopimelic acid in its cell wall, and madurose in whole-cell sugars. No sporangia, zoospores or fragmentations of vegetative mycelium are observed. From these results, strain No. 6049 is designated as Actinomadura pulveracea sp. nov. PMID- 4030500 TI - Mycinamicins, new macrolide antibiotics. IX. Chemical ionization mass spectral studies on mycinamicins. AB - Chemical ionization (CI) mass spectra of new macrolide antibiotics, mycinamicins are reported. Protonated molecules (MH+) are observed as base peaks in the CI mass spectra of all components. Fragmentations are mainly restricted to the glycosidic linkages and the resulting aglycone and sugar-derived ions appear regularly in their mass spectra. Moreover, characteristic fragment ions involving carbon-carbon bond fission are found in the CI mass spectra of the epoxyenone containing components, mycinamicins I (1) and II (2). The mechanism for the formation of the ion species is also discussed. PMID- 4030499 TI - New antitumor antibiotics, FR-900405 and FR-900406. II. Production, isolation, characterization and antitumor activity. AB - The new antitumor antibiotics, FR-900405 and FR-900406, were isolated from the culture broth of Actinomadura pulveracea sp. nov. No. 6049. These compounds which contain sulfur in the molecule, represent a novel class of antitumor agents. FR 900405 and FR-900406 are highly active in mice against experimental tumors and exhibit antimicrobial activity against Gram-positive and Gram-negative bacteria and fungi. PMID- 4030501 TI - Inclusion compounds of lankacidin-group antibiotics with cyclodextrins. AB - Lankacidin-group antibiotics formed inclusion compounds with beta-cyclodextrin in molar ratios of about 1:1. These compounds showed remarkably improved water solubility and stability in aqueous solutions. The structure of the inclusion compounds of lankacidin A is proposed based on the facility of their inclusion with beta-cyclodextrin and the results of 1H NMR spectral studies. PMID- 4030502 TI - Synthesis and antitumor activity of spergualin analogues. I. Chemical modification of 7-guanidino-3-hydroxyacyl moiety. AB - Many analogues and derivatives of an antitumor antibiotic, spergualin, were synthesized, and the relationships between the structure and the activity against mouse L-1210 tumor were studied. Both modification of the 15-hydroxyl group and alteration of chain-length of the omega-guanidinoacyl moiety affected the activity. 15-Deoxyspergualin (18, 1-amino-19-guanidino-11-hydroxy-4,9,12 triazanonadecane-10,13-d ion e) and its analogue 25 (1-amino-21-guanidino-11 hydroxy-4,9,12-triazauneicosane-10,13-dio ne) had strong activity, superior to that of spergualin. PMID- 4030503 TI - Cytotoxicity of spergualin and amine oxidase activity in medium. AB - The cytotoxicity of spergualin on cultured L5178Y cells is dependent on the kind of serum contained in culture media. Spergualin has stronger cytotoxicity to L5178Y cells in calf serum (IC50 = 2 micrograms/ml) than in horse serum (IC50 = 60 micrograms/ml). This was thought to be caused by amine oxidase in sera. Because calf serum was rich in amine oxidase and horse serum was very poor. Spergualin was found to be oxidized by either calf serum or amine oxidase purified from beef plasma. Aminoguanidine, an amine oxidase inhibitor suppressed the spergualin effect to inhibit the growth of L5178Y cells in calf serum to the level in horse serum. On the other hand, in horse serum the spergualin cytotoxicity was enhanced by addition of amine oxidase. These results suggested to us that spergualin might be inactive in itself and that the amine oxidase oxidized product might play an essential role in inhibiting the growth of cells. PMID- 4030504 TI - Specific inhibition of glyceraldehyde-3-phosphate dehydrogenase by koningic acid (heptelidic acid). AB - A sesquiterpene named koningic acid has been isolated from a strain of Trichoderma koningii as a potent inhibitor of ATP generation in the glycolytic pathway. From experiments with both cultured mouse carcinoma FM3A cells and isolated enzymes, it was shown that koningic acid is a specific inhibitor of glyceraldehyde 3-phosphate dehydrogenase that catalyzes the conversion of glyceraldehyde 3-phosphate to 3-phosphoglycerate. PMID- 4030505 TI - A new ansamycin antibiotic, naphthomycin H from a Streptomyces species Y 83,40369. PMID- 4030506 TI - New antitumor antibiotic, FR-900405. III. Mechanism of action of FR-900405. PMID- 4030507 TI - Mechanics of the basilar membrane in Caiman crocodilus. AB - Vibration measurements were made at a number of positions near the proximal (basal) end of the basilar membrane, and on the columella footplate, of Caiman crocodilus using a capacitive probe. The measurements established the existence of a mechanical travelling wave in this species. They showed no significant change of mechanical tuning with temperature, and were highly significantly different from previous reports of neural temperature sensitivity (Smolders, J. and Klinke, R. (1984): J. Comp. Physiol. 155, 19-30). Thus the neural sensitivity to temperature change appears not to depend upon basilar membrane mechanics. One interpretation of this is that the basilar membrane passively precedes an active temperature-sensitive filter. It was also found that the limbus supporting the basilar membrane had a measurable, but unturned, vibration and that the effect of draining scala tympani for the measurements was to increase the basilar membrane tuning frequency by a factor of about 1.5. PMID- 4030508 TI - Three-dimensional features of the striated organelle in the vestibular hair cell. AB - The striated organelle, the Friedmann's body, of the vestibular hair cells in normal guinea pigs were examined using a freeze-fracture-etch technique. The striated organelles were composed of periodic parallel loose spirals of two fine fibrils, the thick strands. This main distance was divided by thin strands, and many fine fibrils cross-linked the thick strands to the central thin strands. Stereo-micrography showed that the thin strands were positioned on a different plane from that of the thick strands and that the thin strands were cross-linked with thick strands by fine fibrils in a radiating pattern, giving them a columnar appearance. PMID- 4030509 TI - The spiral ganglion and cochlear nuclei of deafness mice. AB - Deafness mice (dn/dn) never develop hearing, but, except for the associated physical defects, have no other known abnormalities. For this study, cochleas and brains of five adult homozygotes (dn/dn) and five adult heterozygotes (+/dn), matched by weight and sex, were prepared for serial section light microscopy. In the homozygotes, the organ of Corti was totally degenerated basally, gradually improving toward the apex where supporting cells, border cells and pillar cells were present; however, the stria vascularis was dystrophic in the apex. The saccular macula was atrophied or dystrophic in seven of the ten homozygote ears. The homozygotes had only 23% of the number of spiral ganglion cells found in the heterozygotes, but they appeared robust. In six of the ears of each group there was clumping of apical spiral ganglion neurons. In the homozygotes, the volume of Rosenthal's canal was 121%, that of the dorsal nuclei was 90%, and that of the ventral cochlear nuclei was 63% of the comparable volumes in heterozygotes. The globular cells of the homozygote ventral cochlear nucleus were 72% of the size of those of heterozygotes. These quantitative morphological abnormalities of the homozygote spiral ganglion and cochlear nuclei may result from organ of Corti atrophy. PMID- 4030510 TI - Development of the embryonic chick's tectorial membrane. AB - The nascent tectorial membrane (TM) is identifiable as early as stage 33 (7th day) as thin, wispy material. By stage 37 (11th day), the dense mesh of the immature TM and fibrous webs (subtectorial threads) that attach the TM to the basilar papilla are distinct but scanty. The TM condenses slightly in its upper face. The growth of the columnar cells and basilar papilla during the following days pulls the TM, lifting it upward, and resembling the cables on a suspension bridge in cross-section. As a result, a large hollow wedge forms. During stages 40-44 (14th-18th days), the columnar cells secrete large amounts of fibrous material, which fills the hollow wedge and condenses into the dense meshes. The honeycombed patterns appear at this time. The supporting cells secrete the fibrous webs. Their secretory activity closely corresponds to that of the columnar cells. The secretory material from both cell types remains attached to the apical ends of their respective cells after secretory activity ends. By hatching (stage 46-21 days), the columnar cells have filled with fibrous material and their cytoplasmic organelles are restricted to the apices. The cytoplasm of supporting cells is relatively clear, with few cytoplasmic remnants of their intense secretory activity earlier. PMID- 4030511 TI - Neurons in the cat's primary auditory cortex distinguished by their responses to tones and wide-spectrum noise. AB - In the cortex of barbiturate-anesthetized cats, area AI was identified by its tonotopic organization, and single neurons in that field were examined with regard to the shapes of their spike count-versus-intensity functions, the organization of their frequency-intensity response areas, and their responses to wide-spectrum noise, using calibrated sealed stimulating systems. Neurons whose pure tone rate intensity functions were monotonic in shape displayed V-shaped response areas that were open-ended at high tone intensities. In contrast, cells displaying nonmonotonic tone intensity functions tended to have circumscribed response areas; these cells were responsive to tones over limited ranges of both frequency and intensity. Monotonic neurons almost always responded to wide spectrum noise stimuli, while nonmonotonic neurons often did not. The mean minimum latent period of monotonic cells (14.0 ms) was significantly shorter than that for nonmonotonic neurons (19.1 ms). For those cells that responded to both tones and noise, minimum latent periods for the two stimuli were similar or identical. Monotonic neurons tended to be horizontally segregated from nonmonotonic neurons across AI's middle cortical layers. The implications of these data for the nature of some neural mechanisms underlying the stimulus selectivity of cortical cells are discussed. PMID- 4030512 TI - Some neural mechanisms in the cat's auditory cortex underlying sensitivity to combined tone and wide-spectrum noise stimuli. AB - In the auditory cortex of nitrous oxide-anesthetized, muscle-relaxed cats, single neurons were studied for their responsiveness to pure tones that were mixed acoustically with simultaneously gated wide-spectrum noise bursts presented using a calibrated sealed stimulating system. The intensities of both the tone and the noise were systematically varied, with a view to ascertaining the sensitivity of cortical cells to a characteristic frequency tone delivered in the presence of a noise mask. Neurons for which wide-spectrum noise provided a net excitatory influence typically displayed a 'strong-signal capture' effect; that is, the cell's responses were dominated by whichever of the two elements of the combined stimulus was the more effective when tested separately. These cells generally had monotonic tone rate intensity functions. Most of the cells that were suppressed by the noise displayed nonmonotonic pure tone rate intensity functions. When nonmonotonic cells were studied with the combined stimulus, the noise was found to produce an intensity-dependent suppression of their tone-evoked responses that could not be overcome by elevating the tone intensity. In contrast, for the minority of monotonic neurons whose tone-evoked responses were suppressed by noise, that suppression could be overcome by raising the tone intensity. None of the cells in the sample responded in a sustained fashion to continuous noise. In each of 11 cases examined, the effect of a continuous noise mask was to elevate tone thresholds and to prolong latent periods for tones; the magnitude of both of these effects depended on the intensity of the continuous noise mask. PMID- 4030513 TI - Influence of steam-flaked, steamed-whole or whole shelled corn on performance and digestion in beef steers. AB - Three trials were conducted to evaluate finishing diets containing 67% steam flaked corn (SFC), steamed-whole corn (SWC) or whole corn (WC). In a feeding trial, steers fed SWC consumed more (P less than .05) dry matter per day (7.6 kg) than those fed WC (7.0 kg) or SFC (6.7 kg). Average daily gain was greater (P less than .05) for steers fed SFC (1.33 kg) and SWC (1.31 kg) than for those fed WC (1.25 kg), and feed efficiency was better (P less than .05) for steers fed SFC (5.06 kg dry matter/kg gain) than for those fed WC (5.62) and SWC (5.79). Carcass characteristics were not different among the three groups. In a digestion trial, method of corn processing did not affect digestibility of dry matter and crude protein. Starch digestibility was greater (P less than .05) for SFC (99.1%) than for SWC (93.8%) and WC (93.0%). There were no differences in nitrogen (N) intake or fecal N among the three diets; however, urinary N was less (P less than .05) for SWC (19 g/d) than for SFC (27 g/d) and WC (32 g/d), and N retention was higher (P less than .05) for the SWC diet. In vitro dry matter digestibility of the SFC diet was higher (P less than .05) than for WC at 4 and 8 h of incubation and higher (P less than .05) than the SWC diet at 8, 12 and 24 h of incubation. In vitro gas production after 6 h was greater (P less than .05) for SFC than for SWC grain, which was greater (P less than .05) than WC.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4030514 TI - Relationship of plasma lipid concentrations to fat deposition in pigs. AB - The time course for changes in plasma free fatty acid and triglyceride concentration after removal of feed was established. Genetically obese and lean lines of pigs, two types of crossbred female pigs and a group of male pigs were used to establish the relationship between circulating free fatty acid or triglyceride concentrations and adiposity. Pigs were weighed, ultrasonically probed for backfat thickness, bled in a fed state and again in the fasted state. Plasma was analyzed for free fatty acid and triglyceride concentration. Fasting increased plasma free fatty acid, but only slightly increased triglyceride concentrations. There were several significant correlations between backfat thickness and plasma lipid concentrations; however, the low magnitude and inconsistency of these correlations precludes use of plasma lipid concentrations as indicators of adiposity in swine. Fasted obese pigs had lower plasma fatty acid concentrations than lean pigs at 2, 4 and 6 mo of age. If these plasma levels represent in vivo mobilization of fat, the results probably contrast with previously reported in vitro results wherein adipose tissue from obese pigs had lipolytic rates expressed on a cellular basis that were equal to or greater than those form lean pigs. PMID- 4030515 TI - Linear body measurements and muscle distribution in F1 Holstein x Friesian intact males. AB - Influence of sire, dietary regimen and slaughter weight on wither height, body depth, heart girth, hip width and percentage of total muscle in each of nine commercial cuts of F1 Holstein X Friesian bulls (N = 260) was studied. Sires were full-blooded or percentage Holstein; dams were commercial and purebred Danish Friesians. The young bulls received 100, 75, 50 or 25% concentrates, with the remainder of the diet provided in the form of silage. Animals were serial slaughtered at 340, 470 or 600 kg. Sire was a significant source of variation in many of the body measurements and muscle distributional variables that were evaluated. It was noted, however, that sire differences in percentage of total dissected muscle in Group III cuts (rib + loin + round + hindshank) of intact male progeny were of the order of 1% or less. Sire X diet and sire X slaughter weight interactions were statistically significant in some analyses. Muscular development in the neck region was more pronounced when bulls were fed a low concentrate diet, rather than high levels of concentrates. Percentages of total muscle in the forequarter were highest (P less than .01) for the 470- and 600-kg bulls. Thus feeding bulls to heavier weights had an adverse effect (P less than .01) on percentage of total muscle in Group III cuts. Dietary influence on linear body measurements and muscle distribution in young, Holstein-cross bulls was negligible. PMID- 4030516 TI - Effect of inorganic selenium supplementation on selenium retention in postweaning swine. AB - A total of 64 weanling pigs was used in a randomized complete-block experiment to evaluate the efficacy of various inorganic Se levels on weekly Se balance measurements over a 5-wk post-weaning period. Four-week-old weaned pigs were fed a 20% protein, corn-soybean meal diet supplemented with 0, .3, .5 or 1.0 ppm Se from sodium selenite. Eight pigs were allotted by weight, litter and sex to each metabolism crate. A 2-d preliminary period followed by a 5-d collection period was conducted for five weekly periods. Feed intake was provided ad libitum but was similar between dietary Se levels. Fecal Se excretion increased each week and with increasing dietary Se level. Apparent digestibility of Se was relatively constant for each period when inorganic Se was fed, averaging approximately 70%, whereas it ranged between 30 to 40% for pigs fed the basal diet during wk 2 through 5. Urinary Se decreased during the postweaning periods for pigs fed the basal diet, but increased linearly as dietary Se increased during the initial 2 wk postweaning period and then quadratically during wk 3 through 5. There was a net loss of Se from the body when the Se-unsupplemented basal diet was fed during the initial 2 wk postweaning, whereupon, it became positive. Selenium retention in pigs supplemented with inorganic Se increased each week of the trial. When Se retention was expressed in relation to Se intake, the resulting regression was linear (R2 = .99), suggesting that Se retention in the postweaning pig increased in direct proportion to the amount consumed when diets contained up to 1.0 ppm Se. PMID- 4030517 TI - Weaning weight response of pigs to simple and complex diets. AB - Five experiments were conducted to determine (1) the value of simple vs complex diets on gains and feed conversion of pigs weaned at a constant age but varying in weight, (2) the optimum postweaning time to change from a complex to a simple diet and (3) the effect of previous treatment on subsequent performance. In the first experiment, pigs were weaned at 3 wk +/- 3 d and assigned within four weight groups (4.1, 5.0, 5.6 and 6.7 kg) to a simple or complex diet that was fed for 28 d. The complex diet improved (P less than .01) pig performance in all weight groups. As anticipated, the heavier pigs (5.6 and 6.7 kg) ate more (P less than .02) and grew faster (P less than .03) than did their lighter weight littermates (4.1 and 5.0 kg). The second experiment involved pigs weaned at 3 wk +/- 3 d that were assigned within two weight groups (4.4 and 6.6 kg) and fed a complex diet for 10 d, after which one-half of each weight group was switched to a simple diet. Pigs fed the complex diet for the entire 24-d period gained faster (P less than .05) and were more efficient (P less than .05) than those changed to the simple diet after 10 d. The heavier weight (6.6 kg) pigs ate more (P less than .02) and gained faster (P less than .02) than did the lighter weight (4.4 kg) pigs.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4030518 TI - Protein requirements of mature working horses. AB - Eighteen mature horses were used to study proteins requirements of working horses. Treatments included intense exercise, medium exercise and maintenance in a 3 X 3 factorial arrangement with three levels of calculated dietary crude protein (CP; 8.5, 7.0 and 5.5%). The horses were on the various exercise-protein treatments for 60 d, then fasted 4 d to evaluate their N status after the treatment period. Exercise had no significant effect on body weight over the feeding and fasting periods. No one exercise or protein treatment expressed the classical low plasma albumin or total protein concentrations of protein-deficient or malnourished animals. Plasma urea N (PUN) concentrations reflected the amount of protein in the diet, with the horses fed the high-protein treatment having the highest PUN concentration (P less than .05). Fasting brought about a significant rise in the urinary percentage of urea + NH3 N, with the highest protein treatment excreting the highest percentage (P less than .05). Because plasma protein concentrations were maintained and labile protein reserves were apparently not depleted, it appears that the lowest protein diet containing 1.9 g digestible protein/W.75 was adequate, regardless of work load. PMID- 4030519 TI - Awards of the American Society of Animal Science. PMID- 4030520 TI - Reevaluation of the role of progesterone in stimulating sexual receptivity in estrogen-treated gilts. AB - Three studies were conducted to examine the role of progesterone in stimulating sexual receptivity in estrogen-treated, ovariectomized gilts. Progesterone was administered either before, simultaneously with, or 48 h after estrogen. In each study, gilts were treated with either a suboptimal or an optimal dosage of estradiol benzoate (EB). Progesterone treatment (600 micrograms/kg BW-1 X injection-1) on alternate days for a total of four injections produced serum concentrations of progesterone that were maximal at 9.4 ng/ml and remained greater than 1 ng/ml for 15 d. Estradiol benzoate was administered 22 d after the first of these progesterone injections. When progesterone was administered concurrently with or 48 h after EB, the dosage was 100 micrograms/kg BW and produced a maximal serum progesterone concentration of 1.8 ng/ml 4 h after treatment. Gilts were placed in an evaluation pen with a boar for 5 min on d 3 and 4 after EB treatment. Traits of interest were total number of mounts by the boar, mounts before the gilt showed the immobilization response, proportion of gilts that showed the immobilization response, and latency from entry of the gilt into the evaluation pen until the immobilization response. In none of the three studies did progesterone improve any of the traits of interest. In each study the immobilization response was observed in a higher proportion of gilts treated with the optimal than in those treated with the suboptimal dosage of EB. Latency from entry of gilts into the evaluation pen until the immobilization response was less on d 4 than on d 3 after EB in all studies.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4030521 TI - Production characters of first-generation cows of a five-breed diallel: reproduction of young cows and preweaning performance of inter se calves. AB - Data from cows of a five-breed diallel involving Angus, Brahman, Hereford, Holstein and Jersey were analyzed. Females were used in inter se matings to produce three second-generation parturitions per cow. Crossbred (CB) cows were 43 d younger (P less than .05), 14 kg heavier (P less than .05) and 2 cm taller (P less than .05) at first calving than straightbred (SB) cows; however, no differences were detected (P greater than .10) between the two groups for pelvic measurements. Although large differences among breed types existed for gestation length, crossbreds generally did not differ from straightbreds for this character. Crossbred cows exhibited a 7.5 d shorter (P less than .05) interval from parturition to first service, but did not exhibit a shorter interval from parturition to conception (P greater than .10). The dairy breeds (Holstein and Jersey) and their crosses exhibited similar postpartum and calving intervals as Angus, while Brahman and their crosses had longer intervals. Crossbred calves were 1.3 kg heavier (P less than .01) and had greater (P less than .01) shoulder and hip dimensions at birth than SB calves, but no difference in the amount of calving difficulty was detected (P greater than .10) between the two groups. Higher (P less than .01) rates of survival to 24 h (3.7%) and to weaning (8.7%) were observed for CB calves compared with SB calves. Heterotic effects for weaning weight (15.2 kg), weaning height (2 cm) and preweaning average daily gain (68 g) were large and illustrate the importance of individual and maternal heterosis for these characters. These results suggest that substantial amounts of heterosis may be retained for survival and weaning characters of calves in early generations of inter se mating of CB. PMID- 4030522 TI - Lifetime (seven years) production of 1/4 and 1/2 Finnish Landrace ewes from Rambouillet, Targhee and Columbia dams under range conditions. AB - Lifetime lamb and wool production of 1/4 and 1/2 Finnish Landrace (Finn) crossbred ewes in comparison with local purebred controls was evaluated under range conditions. A total of 1,234 ewe lambs, representing nine breed groups, were first exposed to breeding at 7 mo of age and subsequently retained with no artificial culling, except for debilitating unsoundness, through 7 yr of production. Mating was to Suffolk sires. Differences among pooled breed groups (1/4 Finns, 1/2 Finns and purebreds) generally were not significant for ewe viability to lambing, percentage of lambs born alive and lamb viability to weaning; nor were differences significant for fertility except among yearlings (12 mo at lambing) where 1/4 and 1/2 Finn fertility exceeded that of purebreds by 217 and 278%, respectively. However, for prolificacy, Finn-crosses were consistently superior to purebreds at all seven ages; 1/4 and 1/2 Finns averaged 24 and 48% higher, respectively, than purebreds. Further, Finn-cross ewes clearly excelled purebreds (P less than .05) in the two overall measures of reproduction- net reproductive rate and weight of lamb weaned. The superiority was sustained through all ages and averaged (over ages 2 through 7 yr) 29 and 49% for net reproductive rate and 24 and 41% for weight weaned, for 1/4 and 1/2 Finns, respectively. Conversely, for wool weight, purebreds were consistently superior at all ages; the lifetime averages of 1/4 and 1/2 Finn fleeces were only 90 and 77% as high, respectively, as those of purebreds. It was concluded, however, that the loss in value of wool production associated with Finn breeding was economically of much less importance than the gains made in weight of lamb weaned. The use of 1/4 and 1/2 Finn-crosses involving the above adapted domestic breeds increased the net value of lifetime production by approximately 18 and 29%, respectively. PMID- 4030523 TI - Effect of receiving diets containing alfalfa and certain feed additives on performance of feeder pigs transported long distances. AB - Three experiments were conducted to determine the effect of receiving diets containing alfalfa meal and certain feed additives on performance of comingled feeder pigs transported 900 to 1,100 km. In Exp. 1, the inclusion of 9.4% dehydrated alfalfa meal in receiving diets for 2 wk resulted in no difference (P greater than .1) in gain or feed conversion from purchase to market compared with pigs fed a basal corn-soybean meal (CS) diet or a diet containing 20% ground whole oats (O). In Exp. 2, pigs fed receiving diets containing 10% dehydrated alfalfa meal had no improvement (P greater than .1) in gain (.60 vs .61 kg/d) or conversion (3.25 vs 3.17) compared with CS-fed pigs. In Exp. 3, pigs fed a receiving diet for 2 wk containing 10% mid-bloom alfalfa ate more (P less than .002) feed daily for 2 wk (.82 vs .76 kg) and overall (P less than .04; 1.92 vs 1.85 kg) and had an improved (P less than .03) daily gain from purchase to market (.61 vs .59 kg) compared with CS-fed pigs. In Exp. 2, pigs fed diets containing 44 mg/kg tylosin (T) gained similar to pigs fed no additive (O) and slower (P less than .01) than pigs fed 110 mg/kg chlortetracycline (CTC; .59, .60 and .63 kg/d), with no significant differences in feed to gain conversion (3.12, 3.23 and 3.18).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4030524 TI - Abstracts: annual meetings of the American Society of Animal Science. PMID- 4030525 TI - In vivo activity of nifurzide and nifuroxazide in intestinal bacteria in man and gnotobiotic mice. AB - Although Gram-negative enteropathogenic bacteria are the target strains of nifurzide and nifuroxazide treatments, neither drug affected faecal counts of in vitro-susceptible Enterobacteriaceae in healthy volunteers. This absence of activity was shown to be due to the poor solubility of the drugs tested. Therefore, effect of high doses of nifurzide was investigated in gnotobiotic mice. Activity against in vitro susceptible enteropathogens was then observed. Normal bacterial cells were replaced in the faeces by elongated, nonseptate and unflagellated mutants. Moreover, the resistance to colonization by enterotoxigenic Escherichia coli and Shigella flexeri of an anaerobic flora of human origin was sharply decreased. PMID- 4030526 TI - The rumen microbiology of seaweed digestion in Orkney sheep. AB - The microbial populations of the rumens of seaweed-fed and pasture-fed Orkney sheep were examined. The populations in the pasture-fed sheep were similar to those of other domestic ruminants fed on land plants, but those of the seaweed fed animals showed major differences in the dominant species. Total ciliate populations were quantitatively similar, but in the seaweed-fed animals Dasytricha ruminantium was one of the most dominant species. No phycomycete fungi or cellulolytic bacteria were found in the seaweed-fed animals, and the bacterial population was dominated by Streptococcus bovis, Selenomonas ruminantium, Butyrivibrio fibrisolvens and lactate-utilizing species. Electron microscopy revealed that spirochaetes and an unidentified filamentous bacterium were probably of major significance in seaweed digestion. The ability of bacterial strains from both groups of animals to metabolize plant and algal constituents was examined. PMID- 4030527 TI - The influence of water on the resistance of spores to inactivation by gaseous ethylene oxide. AB - Standardized conditions for exposure to ethylene oxide were used to evaluate the resistance of spores dried for various times at different relative humidities and temperatures. Spores dried under conditions of high humidity exhibited low resistance to the sterilant, the resistance increasing as the relative humidity (RH) was decreased. Increasing the temperature of drying amplified this effect by reducing the time required for equilibration to a specific RH. Spores dried over a desiccant at 37 degrees C showed a slight rise followed by a fall in resistance. Spores maintained under these conditions for a long period of time increased in resistance. Spores rapidly dried by exposure to low RH, over a desiccant or at elevated temperature, dried unevenly resulting in a heterogeneous population with respect to ethylene oxide resistance. This was expressed as non logarithmic survivor curves. The initial vacuum drawn influences resistance. The resistance of spores dried on aluminium foil increased as the pressure was reduced. The rate at which the pressure was reduced had little effect on resistance, except with highly desiccated spores. Dried spores held at different reduced pressures with humidification, showed no differences in resistance. The implications of these findings in relation to the operation of ethylene oxide sterilization cycles and the preparation and use of biological monitors is discussed. PMID- 4030528 TI - A note on crossing experiments with Aspergillus niger for the production of calcium gluconate. AB - A strong calcium gluconate-producing strain of Aspergillus niger (MN181) was obtained by way of mutagenic treatment. Its growth was very slow with moderate sporulation. The strain was treated with N-methyl-N'nitro-N-nitrosoguanidine (MNNG) and some auxotrophic mutants were obtained. All were less productive than the parent strain in producing calcium gluconate. The reduced yield was corrected in the heterokaryons and diploids derived by crossing sister strains. One diploid strain (D4), heterozygous for auxotrophy and conidial colour markers was grown in the presence of 4% alcohol and 31 segregants were isolated which included both haploid and diploid strains. Their yields were studied and some recombinants were obtained which, in spite of the same yield of MN181, showed improvement in giving fast growth and abundant sporulation. PMID- 4030529 TI - Contamination and bacterial retention capacity of beef carcasses at the abattoir. AB - The contamination of beef carcasses was studied together with the capacity of meat surfaces to retain bacteria along the processing line in the slaughter hall. The results showed that the contamination varied along the processing line, but that this pattern was essentially dependent on the contamination at the dressing station. It decreased or remained unchanged during the first 12 min and then increased, even without additional contamination. The contamination varied according to carcasses and micro-organisms studied and was not greatly affected by spray cleaning. The number of bacteria retained changed at a rate similar to that of the contaminants. The attachment was instantaneous. The results are discussed and compared with the various hypotheses about contamination and bacterial attachment processes. PMID- 4030531 TI - Rationalization of terminology and methodology in the study of antibiotic interaction. PMID- 4030530 TI - Bacteria in bivalve shellfish with special reference to the oyster. AB - The bacterial flora of the Pacific oyster Crassostrea gigas, the sea mussel Perna viridis and the arkshell clam Scapharca cornea differed considerably from that of seawater in both numbers and generic composition. The numbers of heterotrophic bacteria in the bivalve shellfish, including the anaerobes and spore-forming bacteria, were greater than that in the surrounding water. Pseudomonas spp. were the dominant organisms, comprising over one third of the 321 strains characterized after isolation from the bivalves and seawater. Other bacteria isolated from the shellfish included Vibrio, Acinetobacter, and Aeromonas spp., whereas the seawater flora consisted mainly of coliform organisms, coryneform bacteria and Flavobacterium/Cytophaga spp. Bacteria associated with the deposit feeding clams were higher in density and more distinct in generic composition as compared with those in the suspension-feeding oysters and mussels. Over 90% of the coliform and heterotrophic bacteria in oysters were found in organs associated with the digestive tract. Coliforms were mainly found in the stomach while heterotrophs were present in both stomach and the lower intestine. The results suggest that the stomach flora of oysters are mainly derived from the external environment and, through a process of selection and multiplication, that it may be gradually replaced by a more indigenous population which dominates the lower digestive tract. PMID- 4030532 TI - Determination of molecular hydrogen in investigations of the susceptibility of Enterobacteriaceae to ampicillin. AB - One hundred and five enterobacterial isolates from urinary tract infections were examined for ampicillin-susceptibility by measurement of molecular hydrogen production with a palladium metal oxide semi-conductor (Pd-MOS sensor). Eighty one per cent of hydrogen producing strains could be placed in the same susceptibility groups as recorded by disc-diffusion tests. However, it was harder to separate susceptible from intermediate types than to determine resistance. In all but five strains the hydrogen production allowed determination of viability within 5 h. PMID- 4030533 TI - Gentamicin administered in vivo reduces protein synthesis in microsomes subsequently isolated from rat kidneys but not from rat brains. AB - Gentamicin injected in vivo, in doses equivalent to those used therapeutically in humans, produced a decrease in the protein synthesizing capacity of microsomes subsequently isolated from rat kidneys, but not of microsomes isolated from rat whole brains. The decreases in eukaryotic cell protein synthesis observed following in-vivo administration of gentamicin were similar to those observed following the addition of gentamicin to microsomes in vitro. PMID- 4030534 TI - Inability of gentamicin and fosfomycin to eliminate intracellular Enterobacteriaceae. AB - The ability of gentamicin and fosfomycin to kill Salmonella typhimurium and Escherichia coli in a HeLa cell culture system was investigated. Antibiotic activity against extracellular, cell membrane-attached and intracellular bacteria were determined. Both gentamicin and fosfomycin had the same low ability to kill intracellular bacteria. The efficacy of fosfomycin against extracellular bacteria was also low, whereas gentamicin rapidly killed such bacteria. These observations show that intracellular enterobacteria are protected from the bactericidal activity of gentamicin and fosfomycin. PMID- 4030535 TI - Stimulatory effects of carbenicillin and ticarcillin on the adhesion and spreading of human polymorphonuclear leukocytes. AB - The in-vitro effects of ticarcillin and carbenicillin on adhesiveness, spreading, chemotaxis, phagocytosis and Candida-killing of human leukocytes have been comparatively studied. Adhesion and spreading of cells was increased by incubation with ticarcillin and carbenicillin. We found significant enlargement of surface and length measurements by optical and scanning electron microscopic examination. (P less than 0.0005). The number of cells was only significantly increased after exposure to ticarcillin (P less than 0.05). There were no modifications of chemotaxis, phagocytosis and Candida-killing capacity with respect to control values. PMID- 4030536 TI - Investigations on the influence of liver diseases on ampicillin body levels in man. AB - Ampicillin bioavailability was examined using the urinary excretion method, in healthy subjects and patients with: viral hepatitis, primary hepatocellular carcinoma and hepatosplenic schistosomiasis. A single dose of 500 mg ampicillin was administered intravenously in each case. Viral hepatitis patients gave similar results to healthy subjects. Primary hepatocellular carcinoma and hepatosplenic schistosomiasis patients had reduced drug bioavailability compared to healthy subjects (P less than 0.001). PMID- 4030537 TI - Vancomycin and netilmicin as first line treatment of peritonitis in CAPD patients. AB - The first line treatment of peritonitis in patients on continuous ambulatory peritoneal dialysis (CAPD) in our hospital was recently altered from a combination of gentamicin and clindamycin, given as continuous peritoneal lavage, to one of vancomycin and netilmicin given in peritoneal dialysis fluid with prolonged dwell time (4-6 h). The change was prompted by the emergence of multiply resistant Staphylococcus epidermidis among CAPD patients and nursing staff. In 9 of 19 episodes of peritonitis treated with gentamicin/clindamycin, the infecting organism could still be isolated from peritoneal fluid 5-15 days after commencement of therapy. All of 35 culture verified episodes treated with vancomycin/netilmicin were cleared bacteriologically within 3 days (P less than 0.0005). The vancomycin and netilmicin serum levels achieved were 6.5-37.0 mg/l and 1.0-8.1 mg/l, respectively. Apart from an asthmatic reaction, possibly triggered by vancomycin, no side effects were seen. However, audiometry was not performed regularly and the possible effect of netilmicin on the residual renal function was not systematically investigated. PMID- 4030538 TI - Intravenous Augmentin in bacteraemia and severe invasive polymicrobial sepsis. AB - An intravenous formulation of Augmentin was used as sole chemotherapy in the treatment of patients with severe infections. Fourteen of 17 assessable patients (82%) responded satisfactorily including six with bacteraemia. Adverse reactions occurred in 38% of patients but in all but one, withdrawn due to diarrhoea, were trivial. There was no significant intolerance. PMID- 4030539 TI - Vancomycin toxicity: a prospective study. AB - A prospective study of 34 patients treated with 39 courses of intravenous vancomycin, was undertaken in order to assess toxicity. Six patients received vancomycin alone and 27 courses were associated with aminoglycoside administration either concurrently or within two weeks of the first dose of vancomycin. Hearing loss was slight and uncommon; patients were unaware of its occurrence. Tinnitus and dizziness was noted by two patients and resolved on withdrawal of vancomycin. Diminution of renal function was seen both during (7%) and after (9%) vancomycin therapy. A striking feature of these patients with renal deterioration was the severity of their underlying disease. No evidence of synergistic toxicity between vancomycin and aminoglycosides was seen. PMID- 4030540 TI - Reduced ampicillin bioavailability following oral coadministration with chloroquine. AB - Ampicillin bioavailability was examined in seven healthy adult male volunteers after oral coadministration with chloroquine using the urinary excretion method. Ampicillin (500 mg, capsules) and chloroquine phosphate (250 mg, tablets) were administered in single doses of 1.0 g each. Each subject received, on two different occasions, ampicillin alone and ampicillin together chloroquine. Urine was collected hourly for 8.0 h. Ampicillin urinary levels were measured chemically. The mean % dose excreted, maximum peak of excretion and the time of that peak after the administration of ampicillin alone were: 29 +/- 4.1%, 1.73 +/ 0.27 mg/min and 1.75 +/- 0.164 h, respectively. The corresponding values after coadministration of ampicillin with chloroquine were: 19 +/- 2.9%, 1.25 +/- 0.17 mg/min and 1.82 +/- 0.210 h. The results indicate a significant reduction (P less than 0.005) in ampicillin bioavailability following oral coadministration with chloroquine. The reduction of ampicillin bioavailability produced by chloroquine might be attributed to slowing of gastric emptying and enhancement of gut motility induced by the chloroquine. PMID- 4030541 TI - Aminoglycoside toxicity. PMID- 4030542 TI - Does the protein binding of antibiotics affect their antistaphylococcal activity? PMID- 4030543 TI - Human serum albumin for in-vitro tests. PMID- 4030544 TI - Sch 34343--a new parenteral penem. Based mainly on papers presented at the 24th Interscience Conference on Antimicrobial Agents and Chemotherapy. Washington, DC, 8-10 October 1984. PMID- 4030545 TI - Synthesis and preliminary in-vitro profile of Sch 34343--a new penem antibacterial agent. AB - Sch 34343, a new penem antibiotic, has been synthesized by several routes and found to be highly active against both aerobic and anaerobic Gram-positive and Gram-negative organisms (except Pseudomonas). It has excellent beta-lactamase stability and is bactericidal. The synthetic routes to Sch 34343 and its in-vitro activity compared with other structurally related penems are discussed. PMID- 4030546 TI - Comparative in-vitro activity of Sch 34343 for a wide spectrum of clinically significant anaerobic bacteria. AB - One hundred and fifty strains of anaerobic bacteria including 45 bacteroides, 19 fusobacteria, 41 cocci, 34 clostridia, and 11 Gram-positive non-sporeforming rods were tested by agar dilution for their susceptibilities to cefoxitin, cefuroxime, latamoxef (moxalactam), penicillin G, chloramphenicol, clindamycin, metronidazole and Sch 34343. Excluding the 34 clostridia, 115 of the 116 remaining strains were inhibited by less than or equal to 1 mg/l of Sch 34343. One isolate of Bacteroides fragilis required 32 mg/l for inhibition. All of the 34 clostridia were inhibited by less than or equal to 8 mg/l of Sch 34343: 14 isolates of Clostridium difficile had an MIC50 and an MIC90 of 4 mg/l, whereas the remaining 20 species of clostridia had an MIC50 of 0.125 mg/l and an MIC90 of 2 mg/l. On a weight basis, Sch 34343 was generally more active than any of the seven other antimicrobial agents tested. PMID- 4030547 TI - Susceptibility of anaerobic bacteria to Sch 34343 and other beta-lactam antibiotics. AB - The in-vitro activity of Sch 34343 was evaluated against 381 anaerobic clinical isolates and compared with that of imipenem, cefoxitin, latamoxef (moxalactam), cefotaxime and cefoperazone. Test isolates included strains with unknown resistance to the beta-lactam drugs, and two Bacteroides fragilis strains that could inactivate cefoxitin. Sch 34343 and imipenem demonstrated superior activity against all the anaerobic bacteria tested, with MIC90s less than or equal to 1 mg/l. Sch 34343 was generally one- to two-fold more active than imipenem. Resistance to both was demonstrated by the two Bact. fragilis strains that inactivated cefoxitin and by one strain of Fusobacterium; these three strains were also resistant to the other drugs studied. There were no other resistant strains to either Sch 34343 or imipenem. Cefotaxime and cefoperazone were the least active against the Bact. fragilis group, with resistance rates of 33 and 47%, respectively. Strains resistant to cefoxitin, latamoxef, cefotaxime and cefoperazone were found among some Clostridium spp. The Gram-positive cocci and Gram-positive bacilli were sensitive to all the drugs evaluated. PMID- 4030548 TI - Susceptibility of anaerobic bacteria to Sch 34343 and other antibiotics. AB - The in-vitro activity of Sch 34343 was evaluated against 137 strains of anaerobic bacteria by the agar dilution technique. Sch 34343 was compared with imipenem, cefoxitin, latamoxef (moxalactam), clindamycin and metronidazole. Organisms studied included the Bacteroides fragilis group, other Bacteroides spp., Clostridium perfringens, Cl. difficile, other Clostridium spp. and anaerobic cocci. Overall, Sch 34343 and imipenem were significantly more active than the other antibiotics against most organisms tested, especially the Bact. fragilis group, including clindamycin-resistant strains. Apart from Cl. difficile, which required up to 8 mg/l of Sch 34343 and imipenem for inhibition, all the strains were inhibited by 1 mg/l of Sch 34343 and by 2 mg/l of imipenem. Of the remaining agents tested, against the Bact. fragilis group metronidazole (2 mg/l to inhibit 90% of the strains) was the most active, followed by cefoxitin (16 mg/l), latamoxef (32 mg/l) and clindamycin (32 mg/l). On the basis of its activity in vitro, Sch 34343 appears to be one of the most promising new antimicrobial agents for the treatment of infections involving anaerobic bacteria. PMID- 4030549 TI - Pharmacokinetics of Sch 34343 in rats and dogs. AB - The pharmacokinetics of 14C-Sch 34343 were studied in rats and dogs following intravenous and intramuscular dosing. In both species, it was rapidly absorbed after intramuscular dosing. The serum AUC for total radioactivity and for intact drug after intramuscular dosing were similar to those obtained after intravenous dosing. Following both routes of drug administration, the elimination of half life (T 1/2 beta) was 7 min in rats and 25-32 min in dogs. Following intravenous dosing of 14C-Sch 34343 to rats, radioactivity in tissues disappeared rapidly with time indicating no tissue accumulation. Highest concentrations of radioactivity were seen in the kidney. Liver, lung, skin and heart appeared to have concentrations of radioactivity similar to those of blood. Sch 34343 was excreted rapidly and primarily into the urine in both rats and dogs. After either route of dosing, urinary excretion of total radioactivity ranged from 84 to 93% and that of intact Sch 34343 from 41 to 51% of the dose, respectively. In addition, the effect of pretreatment with probenecid on the pharmacokinetics in rats and dogs and in anephric rats were also evaluated. Pretreatment with probenecid prolonged the elimination half-life in both rats and dogs. Anephric rats had a longer half-life than normal rats. PMID- 4030550 TI - Interspecies pharmacokinetic scaling of Sch 34343. AB - Pharmacokinetic parameters of Sch 34343 have been determined for mice, rats, rabbits, monkeys, dogs and humans and correlated among species as an exponential function of body weight. The pertinent pharmacokinetic parameters tested are apparent and steady-state volumes of distribution, total body clearance, elimination phase half-life, and mean residence time. This study showed that the extrapolation of animal data to humans on a new investigational drug, Sch 34343, can be potentially useful. PMID- 4030551 TI - In vivo 31P-NMR in human muscle: transient patterns with exercise. AB - Evaluation of dynamic changes in pH and concentrations of adenosine 5' triphosphate (ATP), phosphocreatine (PCr), and inorganic phosphate (Pi) during the transition from rest to steady-state exercise in the human has been methodologically limited. Previous work has relied on muscle biopsy of exercising subjects at different times in different exercise bouts. Chemical evaluation of metabolites has been hampered by continuing change in metabolic concentration during the biopsy procedure. Recently, Fourier-transformed 31P nuclear magnetic resonance (31P-NMR), employing surface coils, has made evaluation of phosphorus metabolites possible by noninvasive atraumatic means in human muscle. Relative concentrations of PCr, Pi, and ATP, together with pH, have been obtained with 31P NMR from the flexor digitorum superficialis muscle on two occasions in four adult men during the transition from rest to exercise. [PCr] rapidly fell and was mirrored by a rise in [Pi]. The former temporarily exceeded the latter with the discrepancy apparently being absorbed by a transient rise in [ATP], which was itself mirrored by alteration in [H+]. PMID- 4030553 TI - Injury to skeletal muscle fibers of mice following lengthening contractions. AB - We tested the hypothesis that lengthening contractions result in greater injury to skeletal muscle fibers than isometric or shortening contractions. Mice were anesthetized with pentobarbital sodium and secured to a platform maintained at 37 degrees C. The distal tendon of the extensor digitorum longus muscle was attached to a servomotor. A protocol consisting of isometric, shortening, or lengthening contractions was performed. After the contraction protocol the distal tendon was reattached, incisions were closed, and the mice were allowed to recover. The muscles were removed after 1-30 days, and maximum isometric force (Po) was measured in vitro at 37 degrees C. Three days after isometric and shortening contractions and sham operations, histological appearance was not different from control and Po was 80% of the control value. Three days after lengthening contractions, histological sections showed that 37 +/- 4% of muscle fibers degenerated and Po was 22 +/- 3% of the control value. Muscle regeneration, first seen at 4 days, was nearly complete by 30 days, when Po was 84 +/- 3% of the control value. We conclude that, with the protocol used, lengthening, but not isometric or shortening contractions, caused significant injury to muscle fibers. PMID- 4030552 TI - Hypoxia-induced activation in small isolated pulmonary arteries from the cat. AB - Effects of hypoxia on force development and membrane potential were studied in isolated small (less than 300 microns diam) and large (greater than 500 microns diam) pulmonary arteries from cats. There was a consistent and reproducible hypoxic constrictor response in small pulmonary arteries that began at PO2 values between 350 and 300 Torr and reached a maximum at PO2 between 50 and 30 Torr. In the small artery smooth muscle cell the membrane potential, which was -51 +/- 1.4 mV at a PO2 of 400 Torr, was depolarized to -37 +/- 2 mV at a PO2 of 50 Torr. In contrast, larger arteries did not exhibit significant hypoxic constriction or depolarization upon exposure to low PO2. Constriction in small arteries was not blocked by phentolamine. Treatment with a low dose of indomethacin (10(-9) M) augmented the response; however, a larger dose of indomethacin (10(-3) M) blocked the constriction to hypoxia but not to 30 mM KCl. Depolarization during hypoxia was not blocked by ouabain. Results of this study suggest that the hypoxic response of these isolated small pulmonary vessels may be like that seen in the intact lung. Furthermore, these data suggest that hypoxic vasoconstriction may be mediated by electrical events occurring at the pulmonary arterial muscle cell membrane either directly or via mediators released from the vessel wall. PMID- 4030554 TI - Free, glucuronide, and sulfate catecholamines in the rat: effect of hypoxia. AB - The formation and excretion of conjugated catecholamines (CA) was studied in conscious rats after sympathetic stimulation by hypoxia (5.5-6% O2, 4 h). Hypoxia induced a rapid and intense increase of free epinephrine (E, X 12) and norepinephrine (NE, X 6) but only a limited enhancement of free dopamine (DA, X 2). Sulfate conjugates of E and NE had kinetics similar to the free forms, while glucuronides were only moderately and lately altered. In contrast to free and sulfated DA, DA glucuronide, the major plasma conjugate, was decreased (-25%). This result suggests that DA glucuronide, unlike other CA conjugates, is not related to detoxication but might supply a CA precursor. Urinary conjugates badly reflected plasma conjugates. In normoxic controls, CA conjugates prevailed in the plasma, whereas the free amines prevailed in the urine. Hypoxia increased mainly the excretion of E and NE glucuronide but not of the free amines. Urinary DA, free or conjugated, was decreased (-25%), a result in keeping with plasma DA glucuronide only. The poor relations between plasma and urine catecholamines pinpoint the importance of the kidney in CA handling. PMID- 4030555 TI - Adaptive response of hypertrophied skeletal muscle to endurance training. AB - The response of hypertrophied soleus and plantaris muscle of rats to endurance training was studied. Hypertrophy was produced by bilateral extirpation of the gastrocnemius muscle. A 13-wk training program of treadmill running initiated 30 days after removal of the gastrocnemius muscle accentuated (P less than 0.01) the hypertrophy. Succinate dehydrogenase activities of the enlarged muscles of sedentary rats were similar to those of normal animals, as were the increases associated with training. Phosphorylase and hexokinase activities were unaltered as a result of the experimental perturbations. Rates of glycogen depletion during exercise were lower (P less than 0.01) in the liver and soleus and plantaris muscles of endurance-trained animals. No difference existed in the rate of glycogen depletion of normal and hypertrophied muscle within the sedentary or trained groups. These data demonstrate that extensively hypertrophied muscle responds to training and exercise in a manner similar to that of normal muscle. PMID- 4030556 TI - Muscle performance and metabolism in maximal isokinetic cycling at slow and fast speeds. AB - To provide a description of the metabolic changes in muscle during maximal dynamic exercise, muscle biopsies were obtained in five healthy subjects before and after 30 s of isokinetic exercise at two pedaling frequencies (60 and 140 rpm) associated with contrasting fatigue characteristics. Higher peak power was attained at 140 rpm (1,473 + 185 W) (mean +/- SE) than at 60 rpm (1,122 +/- 70 W), but the decline in power during 30 s (fatigue index) was greater at 140 rpm (61.6 +/- 3.2 vs. 21.5 +/- 2.4%), total work in 30 s being similar (18.1 +/- 1.10 vs. 20.1 +/- 1.10 kJ). Changes in the concentration of muscle metabolites were similar; creatine phosphate concentration fell to approximately 50% of resting values, and the glycolytic intermediates glucose 6-phosphate, fructose 6 phosphate, and fructose 1,6-biphosphate increased up to 30-fold. Muscle lactate concentration ([La-]) was 29.0 +/- 3.98 and 31.0 +/- 4.31 mmol/kg wet wt immediately postexercise at 140 and 60 rpm, respectively. Even after only 10 s exercise (n = 2), large increases were measured in glycolytic intermediates and [La-]. In the two subjects, muscle [La-] increased to 17.2 and 15.1 mmol/kg at 140 rpm and to 14.3 and 14.2 mmol/kg at 60 rpm. In this type of exercise, glycogenolysis is activated very rapidly at both pedal speeds; the changes in glycolytic intermediates were consistent with rate-limiting steps at the phosphofructokinase and pyruvate dehydrogenase reactions. The greater fatigue at the higher speed is not accompanied by different biochemical changes than at 60 rpm. PMID- 4030557 TI - Calcium uptake in mitochondria from different skeletal muscle types. AB - The kinetics of calcium (Ca2+) uptake have been studied in mitochondria isolated from the different types of skeletal muscle. These studies demonstrate that the Ca2+ uptake properties of skeletal mitochondria are similar to those from liver and cardiac mitochondria. The Ca2+ carriers apparently have a high affinity for Ca2+ (Michaelis constants in the microM range). The relationship between Ca2+ uptake and initial Ca2+ concentration (10(-5) to 10(-7) M) is sigmoid in all mitochondria from the different skeletal muscle types suggesting that the uptake process is cooperative. Hill plots reveal coefficients of approximately 2 for mitochondria from fast-twitch muscle and 3.5 for slow-twitch muscle, adding further evidence to the concept that the uptake process is cooperative. An analysis of the potential role of mitochondria in the sequestration of Ca2+ during muscular contraction demonstrated that mitochondria from slow-twitch muscle of both rats and rabbits can potentially account for 100% of the relaxation rate at a low frequency of stimulation (5 Hz). In fast-twitch muscle, the mitochondria appear unable to play a significant role in muscle relaxation, particularly at stimulation frequencies that are considered in the normal physiological range. In summary, it appears that Ca2+ uptake by mitochondria from slow-twitch skeletal muscle has kinetic characteristics which make it important as a potential regulator of Ca2+ within the muscle cell under normal physiological conditions. PMID- 4030558 TI - Creatine kinase-MB isoenzyme adaptations in stressed human skeletal muscle of marathon runners. AB - The creatine kinase (CK) isoenzyme composition was determined in serial gastrocnemius muscle biopsies obtained from 12 male marathon runners. The mean muscle CK-MB composition significantly increased after chronic exercise (training) from 5.3% (pretraining) to 7.7% (premarathon) as well as after acute exercise (postmarathon) to 10.5% of the total CK activity (P less than 0.05). However, no significant differences in total CK activities were detected. Additionally, mitochondrial CK and CK-BB isoenzymes were present in muscle homogenates. A significant correlation was observed in the increase in mean serum total CK (3,322 U/l) and CK-MB (174 U/l) activities 24 h after the race (r = 0.98, P less than 0.05). These results show that gastrocnemius muscle adapts to long-distance training and racing with increased CK-MB activities and imply that skeletal muscle is the major source of elevated serum CK-MB activities in marathon runners. PMID- 4030560 TI - Effect of the larynx on oscillatory flow in the central airways: a model study. AB - Measurements were made of the effect of the larynx on the oscillatory flow profiles in a 3:1 scale model of the human central airways. A fixed glottic aperture corresponding to the shape and size at midinspiration was used. Oscillatory airflows at peak Reynolds numbers, similar to those obtained during spontaneous breathing and panting, were studied. The flow distribution to the five lobar bronchi was maintained by distally placed linear resistors. A hot-wire anemometer probe was used to measure the local velocity along two perpendicular diameters at six stations distributed through the model. Near the proximal end of the trachea, the flat velocity profiles at the beginning of the flow cycle peaked at maximum flow because of the jet created by the glottic aperture. This peaked structure was conserved during the latter half of the inspiratory cycle. Close to the carina, the jet had almost dissipated and the entry conditions into the main bronchi corresponded to those in the absence of the laryngeal model. The effect of the glottic aperture on the mean velocity was not felt beyond the carina, and the characteristic skewed profiles seen in oscillatory flows, in the absence of the larynx, were present in the main and lobar bronchi. PMID- 4030559 TI - Effects of elevated and exercise-reduced muscle glycogen levels on insulin sensitivity. AB - The effects of an exercise-induced muscle glycogen reduction and an elevated muscle glycogen concentration on glucose tolerance and the insulin response to an oral glucose tolerance test (GTT) were examined. GTTs were administered to seven male subjects after 3 days on a mixed diet (C), after exhaustive exercise and 1 day on a high-fat protein diet (L-FP), after exhaustive exercise and 1 day on a mixed diet (L-M), and after exhaustive exercise and 3 days on a high-carbohydrate diet (H-CHO). The L-M treatment resulted in a significant reduction in muscle glycogen (C, 79.6 +/- 4.2 mmol/kg wet wt vs. L-M, 53.9 +/- 1.2 mmol/kg wet wt) and a 31.7% reduction in the insulin-glucose (IG) index, a measure of insulin sensitivity in vivo. Muscle glycogen was also significantly reduced by the L-FP treatment (49.1 +/- 2.4 mmol/kg wet wt), but there was no change in the IG index. Preventing a decrease in the IG index during the L-FP treatment may have been a result of elevated free fatty acids (67%) and ketones (552%) prior to the GTT. Muscle glycogen was significantly increased by the H-CHO treatment (124.8 +/- 11.1 mmol/kg wet wt); however, the IG index was not different from that of the C treatment. The results suggest that an exercise-induced reduction in muscle glycogen can improve insulin sensitivity in vivo but that this effect is diet dependent. PMID- 4030561 TI - Respiration of conscious kittens in acute hypoxia and effect of almitrine bismesylate. AB - Respiration was measured noninvasively in conscious kittens at an ambient temperature of 28-32 degrees C. Inspired O2 fraction (FIO2) was reduced abruptly from 0.21 to 0.12, 0.10, or 0.08 for 5 min on the day of birth and then on days 4, 7, 14, and 28. The ventilatory response to hypoxia was biphasic, as reported previously in anesthetized kittens, with minute ventilation (VE) increasing in the first minute and then falling towards control over the next 4 min. The fall in VE was due to a consistent fall in tidal volume, the changes in frequency during the second phase being more variable. The size of the first phase of the response increased up to 14 days, but the time at which the peak increase in VE occurred was not correlated with age. The degree of the secondary fall in VE was similar at each age and at each FIO2 studied. The degree of the biphasic response was significantly reduced after administration of almitrine (2 mg/kg ip) on days 1 and 4, but almitrine did not affect the response in older kittens. PMID- 4030562 TI - Dynamic exercise training in foxhounds. I. Oxygen consumption and hemodynamic responses. AB - Ten foxhounds were studied during maximal and submaximal exercise on a motor driven treadmill before and after 8-12 wk of training. Training consisted of working at 80% of maximal heart rate 1 h/day, 5 days/wk. Maximal O2 consumption (VO2max) increased 28% from 113.7 +/- 5.5 to 146.1 +/- 5.4 ml O2 X min-1 X kg-1, pre- to posttraining. This increase in VO2max was due primarily to a 27% increase in maximal cardiac output, since maximal arteriovenous O2 difference increased only 4% above pretraining values. Mean arterial pressure during maximal exercise did not change from pre- to posttraining, with the result that calculated systemic vascular resistance (SVR) decreased 20%. There were no training-induced changes in O2 consumption, cardiac output, arteriovenous O2 difference, mean arterial pressure, or SVR at any level of submaximal exercise. However, if post- and pretraining values are compared, heart rate was lower and stroke volume was greater at any level of submaximal exercise. Venous lactate concentrations during a given level of submaximal exercise were significantly lower during posttraining compared with pretraining, but venous lactate concentrations during maximal exercise did not change as a result of exercise training. These results indicate that a program of endurance training will produce a significant increase in VO2max in the foxhound. This increase in VO2max is similar to that reported previously for humans and rats but is derived primarily from central (stroke volume) changes rather than a combination of central and peripheral (O2 extraction) changes. PMID- 4030563 TI - Neural and humoral factors in control of tracheal caliber. AB - To assess the contributions of neural (vagal) and humoral (blood borne) mechanisms in the tracheal constriction that occurs when pump ventilation is transiently withheld, experiments were conducted on decerebrate dogs. The dogs were paralyzed and thoracotomized, and each lung was independently ventilated. Pressure changes within an isolated tracheal segment (Ps) were monitored as an index of tracheal caliber. In series I, pump ventilation was withheld 20 s at the prevailing end-expiratory pressure (3-5 cmH2O) from both lungs or either lung alone when 1) both lungs were intact; or 2) the left lung was vascularly isolated (VIL) by occluding the pulmonary artery and the right gas exchange lung (GEL) was vagally denervated. In series II, steady-state pressure changes in the VIL were made with constant GEL ventilation. With both lungs intact, 20-s apnea elicited a 17.3 +/- 2.6 cmH2O increase in Ps; the left and right lungs contributed equally to this response. Following vagotomy and pulmonary arterial occlusion, a 7.8 +/- 2.6 cmH2O increase in Ps was elicited from two lungs; the VIL response was 60 +/- 11% and the GEL 41 +/- 15%. Onset and one-half response times were faster from the VIL than GEL. Prolonged maneuvers elicited progressively larger responses from the GEL, but the VIL response plateaued within 30 s and then adapted towards the control level. In series II, steady-state increases or decreases in VIL pressure elicited small decreases or increases in Ps, respectively, which showed nearly complete adaptation within several minutes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4030564 TI - Kinetics of oxygen uptake and heart rate at onset of exercise in children. AB - Requirements for cellular homeostasis appear to be unchanged between childhood and maturity. We hypothesized, therefore, that the kinetics of O2 uptake (VO2) in the transition from rest to exercise would be the same in young children as in teenagers. To test this, VO2 and heart rate kinetics from rest to constant work rate (75% of the subject's anaerobic threshold) in 10 children (5 boys and 5 girls) aged 7-10 yr were compared with values found in 10 teenagers (5 boys and 5 girls) aged 15-18 yr. Gas exchange was measured breath to breath, and phases I and II of the transition and phase III (steady-state exercise) were evaluated from multiple transitions in each child. Phase I (the VO2 at 20 s of exercise expressed as percent rest-to-steady-state exercise VO2) was not significantly correlated with age or weight [mean value 42.5 +/- 8.9% (SD)] nor was the phase II time constant for VO2 [mean 27.3 +/- 4.7 (SD) s]. The older girls had significantly slower kinetics than the other children but were also found to be less fit. When the teenagers exercised at work rates well below 75% of their anaerobic threshold, phase I VO2 represented a higher proportion of the overall response, but the phase II kinetics were unchanged. The temporal coupling between the cellular production of mechanical work at the onset of exercise and the uptake of environmental O2 appears to be controlled throughout growth in children. PMID- 4030565 TI - Expiratory effects of vagal stimulation in newborn kittens. AB - Expiratory effects of electrical stimulation of vagal afferents were studied in 12 kittens during the first week of life. Animals anesthetized with ketamine (30 mg/kg, im) and acepromazine (1.1 mg/kg, im), tracheostomized, and paralyzed were artificially ventilated after bilateral vagotomy. Rectified and "integrated" activity of the C5 root of phrenic nerve, systemic blood pressure, and the stimulus train were recorded. The optimal stimulus parameters for expiratory prolongation were chosen. The results varied between animals. We found three types of response: A, expiratory prolongation when stimulus was applied within the initial 80% of control expiratory time (TEc); beyond this delay, a decreased response or no effect was observed in four kittens; B, graded expiratory prolongation was recorded to the end of this phase in three kittens; and C, expiratory prolongation when stimulus delay was less than 40% of TEc and expiratory shortening when the stimulus given with greater delays was observed in one kitten. Nonsignificant effects were observed in the remaining four animals. Types A and B of response suggest activation of the slowly adapting pulmonary stretch receptors. However, amplitude of stimulus and frequency of pulses were higher than those used in adult animals. Type C response indicates that fibers from both rapidly and slowly adapting stretch receptors could be activated. Our results imply that if the expiratory insensitive phase is present in kittens, it can be affected by experimental conditions. This is in contradiction to characteristics of expiratory response to vagal stretch receptor input in adult cats. PMID- 4030566 TI - Influence of nicotine in cigarette smoke on acute ventilatory responses in awake dogs. AB - To determine whether the acute ventilatory responses to inhaled cigarette smoke are affected by a difference in nicotine level, control cigarettes (low-nicotine research cigarettes) were laced with nicotine to generate an increase of 330% (mean) in nicotine content with little or no change in the levels of other smoke constituents. Acute ventilatory responses to both control and nicotine-laced cigarettes were determined and compared in six awake chronic dogs. Spontaneous inhalation of nicotine-laced cigarette smoke (10% concn, 750 ml vol) via a tracheostomy tube caused distinct and consistent changes in breathing pattern on the first or second breath of inhaled smoke: an apnea in three dogs, an augmented inspiration in two dogs, and rapid shallow breathing in one dog. No significant change in breathing pattern was found immediately following inhalation of control cigarette smoke. Both types of cigarettes caused a delayed hyperpnea. However, the increase in minute ventilation induced by nicotine-laced cigarettes (from a base line of 2.8 to a peak of 25.7 l/min) was significantly greater than that by control cigarettes (from 2.9 to 5.5 l/min). Results of this study suggest that nicotine is responsible for the elicitation of both the immediate and delayed ventilatory responses to inhaled cigarette smoke generated under our experimental conditions. PMID- 4030567 TI - Submaximal exercise responses of tetraplegics and paraplegics. AB - This study describes responses of 21 wheelchair users to a continuous, increasing work rate test to exhaustion on a wheelchair ergometer. Heart rate, ventilation, O2 uptake, respiratory exchange ratio, ventilation equivalent for O2, and O2 pulse were determined for each minute. Subjects were divided into tetraplegic (n = 8), high-lesion paraplegic (n = 6), and low-lesion paraplegic (n = 7) groups. Linear regression analyses, with O2 uptake as the independent variable, were used to determine the strength of relationships within each group and differences between groups in slopes and intercepts of regression equations. All variables were significantly (P less than 0.05) related to O2 uptake (r = 0.42-0.94). The only significant difference between the high- and low-lesion paraplegic groups was for heart rate intercept, as the heart rate for the low-lesion group tended to be lower at any given O2 uptake. Tetraplegics had a higher intercept and/or slope for ventilation equivalent, ventilation, and respiratory exchange ratio and lower intercepts for heart rate and O2 pulse. These differences in responses to a progressive exercise task are logically related to the differences in maximal O2 uptake, functional muscle mass, and vasomotor and cardiac control of the groups. PMID- 4030568 TI - Testosterone and muscle hypertrophy in female rats. AB - The effects of chronic treatment with testosterone propionate on compensatory muscle hypertrophy secondary to synergist removal were studied in female rats. Synergist removal resulted in a significant (2-fold) increase in muscle wet weight, with no changes in protein concentration. As reported previously, oxidation of [2-14C]pyruvate to 14CO2 was significantly decreased in hypertrophic muscles. In addition, malate dehydrogenase and lactate dehydrogenase activities were significantly decreased in overloaded muscles on a wet weight basis but not on the basis of noncollagen protein. These data suggest that specific metabolic adaptations may occur in response to overload of muscle. Administration of testosterone propionate in subcutaneously implanted Silastic capsules resulted in a 20-fold increase in serum testosterone levels. This treatment had no effect on body weight, muscle weight, pyruvate oxidation, or malate and lactate dehydrogenase activities in both control and hypertrophic muscles, although there was an effect on the noncollagen protein content of overloaded muscles. These results do not support the hypothesis that androgens, in conjunction with weight bearing exercise in female subjects, are effective in increasing muscle mass or function in female subjects. PMID- 4030569 TI - Comparison of thermal responses between rest and leg exercise in water. AB - This study examined both the thermal and metabolic responses of individuals in cool (30 degrees C, n = 9) and cold (18 degrees C, n = 7; 20 degrees C, n = 2) water. Male volunteers were immersed up to the neck for 1 h during both seated rest (R) and leg exercise (LE). In 30 degrees C water, metabolic rate (M) remained unchanged over time during both R (115 W, 60 min) and LE (528 W, 60 min). Mean skin temperature (Tsk) declined (P less than 0.05) over 1 h during R, while Tsk was unchanged during LE. Rectal (Tre) and esophageal (Tes) temperatures decreased (P less than 0.05) during R (delta Tre, -0.5 degrees C; delta Tes, -0.3 degrees C) and increased (P less than 0.05) during LE (delta Tre, 0.4 degrees C; Tsk, 0.4 degrees C). M, Tsk, Tre, and Tes were higher (P less than 0.05) during LE compared with R. In cool water, all regional heat flows (leg, chest, and arm) were generally greater (P less than 0.05) during LE than R. In cold water, M increased (P less than 0.05) over 1 h during R but remained unchanged during LE. Tre decreased (P less than 0.05) during R (delta Tre, -0.8 degrees C) but was unchanged during LE. Tes declined (P less than 0.05) during R (delta Tes, -0.4 degrees C) but increased (P less than 0.05) during LE (delta Tes, 0.2 degrees C). M, Tre, and Tes were higher (P less than 0.05), whereas Tsk was not different during LE compared with R at 60 min.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4030570 TI - Effects of histamine on bronchial artery blood flow and bronchomotor tone. AB - The effects of aerosolized 5% histamine (10 breaths) on bronchial artery blood flow (Qbr), airflow resistance (RL), and pulmonary and systemic hemodynamics were studied in mechanically ventilated sheep anesthetized with pentobarbital sodium. Histamine increased mean Qbr and RL to 252 +/- 45 and 337 +/- 53% of base line, respectively. This effect was significantly different from base line for 30 min after challenge. The histamine-induced increase in RL was blocked by pretreatment with the histamine H1 receptor antagonist, chlorpheniramine, whereas the histamine-induced elevation in Qbr was prevented by the H2 antagonist, metiamide. Both responses were blocked only when both antagonists were present. Changes in Qbr were not directly associated with alterations in systemic and pulmonary hemodynamics or arterial blood gas composition. In vitro histamine caused a dose dependent contraction of ovine bronchial artery strips that was prevented by H1 antagonist. The H2 agonist, impromidine, caused relaxation of precontracted arterial strips and was more potent and efficacious than histamine, whereas H1 agonists failed to elicit a relaxant response. Thus these findings indicate that histamine aerosol induces a vasodilation in the bronchial vascular bed; histamine has a direct effect on Qbr that is independent of alterations in RL, systemic and pulmonary hemodynamics, or arterial blood gas composition; and, histamine-induced bronchoconstriction is mediated predominantly by H1-receptors, whereas increased Qbr is controlled predominantly by H2-receptors, probably located in resistance vessels. This local effect of histamine on Qbr may have important implications in the pathophysiology of bronchial asthma and pulmonary edema. PMID- 4030571 TI - Respiratory resistance in dogs by the single-breath and the forced oscillation methods. AB - Total respiratory resistance (Rrs) was measured in six anesthetized dogs with two different methods: the single-breath (SB) method, which provides the time constant of the system during a relaxed expiration and the forced oscillation (FO) method, which uses a pseudorandom noise signal applied at the airway opening. The comparison was made in three conditions: before muscle paralysis (A), after muscle paralysis (B), and after tracheal banding (C). In conditions A and B the two computed resistances correlated very well with each other (r = 0.98). No systematic difference between Rrs values obtained with the two methods was found. In condition C the respiratory resistance was clearly nonlinear from the flow-volume curves during SB and could be described with Rohrer's equation: Rrs = K1 X V + K2 X V2, where K1 and K2 are Kohrer's constant and V is flow. Rrs measured with FO was not frequency dependent during tracheal banding (C) and was virtually equivalent to K1. Since the FO method uses low flows as the input of the respiratory system and K1 could be ascribed to laminar flow, the numerical matching appears reasonable and tends to reinforce the validity of both methods of measurement. We conclude that, for the normal respiratory system, FO and SB methods are approximately equivalent. In the presence of a markedly alinear central airway resistance with normal lungs, the SB method appears to provide a more adequate description of the flow-resistive properties of the system. PMID- 4030572 TI - A technique for unilateral instillation of agents into the rat lung. AB - We describe a technique for unilateral instillation of agents into the right lung of rats. We intubated rats perorally with a 16-gauge flexible polyethylene catheter and through it introduced narrow-bore (less than 1 mm diam) polyethylene tubing into the trachea and beyond the carina into the right main-stem bronchus. This maneuver was facilitated by placing the animal supine with the cephalad end tilted up and the right side tilted down. We tested the effectiveness of our technique by instilling Evans blue dye into the right lung of 14 rats and spectrophotometrically quantitating the amount of dye present in homogenates from each lobe of the right and left lungs. Ninety-seven percent of the instilled dye was recovered from the right lung, and distribution of dye per gram of tissue was uniform among the four lobes. The technique described should be useful in producing severe degrees of unilateral lung injury and fibrosis in rodents without the high mortality that can be associated with bilateral lung injury. PMID- 4030573 TI - Diaphragmatic pressures: transvenous vs. direct phrenic nerve stimulation. AB - Diaphragmatic force, determined by stimulating the phrenic nerve while simultaneously measuring the pressures in a closed respiratory system, was assessed in five anesthetized dogs over a 5-h period to evaluate the inherent variability of this technique. Transdiaphragmatic pressure (Pdi) was measured at functional residual capacity during stimulation (120 Hz, 0.2-ms duration) of one phrenic nerve by either direct phrenic nerve stimulation (DPNS) or transvenous phrenic nerve stimulation (TPNS). An analysis of variance showed no significant (P greater than 0.50) change during the 5-h period. There was a significant correlation (r = 0.94, P less than 0.001) between Pdi obtained by TPNS and that obtained by DPNS. It is concluded that either DPNS or TPNS can be used to evaluate diaphragmatic strength over a 5-h period and that TPNS can be used in lieu of DPNS. PMID- 4030574 TI - Moment analysis of multibreath nitrogen washout in young children. AB - The purpose of this study was to determine whether on-line computerized moment analysis of multibreath N2 washout (MBNW) could be used as a method of estimating lung function in children too young to cooperate with routine pulmonary function testing. The limits of normal variability were determined from results obtained from duplicate studies performed on 36 healthy children ages 3-6 yr. Five healthy adults were studied for comparison. Test sensitivity was estimated by comparing the results in the healthy group to those of 10 age-matched children with cystic fibrosis (CF). Outcome variables of interest included functional residual capacity, the first-to-zeroth moment ratio (M1/M0), the second-to-zeroth moment ratio (M2/M0), and the lung clearance index. Test precision in the healthy group was high with the intrasubject coefficient of variation for all variables being less than 10%. There was no difference in mean within- or among-subject variability between the healthy children and the older, theoretically more cooperative, healthy adults. Mean M1/M0 and M2/M0 were both higher in CF than in the healthy group, 2.69 vs. 2.32 and 13.04 vs. 9.31, respectively (P less than 0.001). Moment ratios in CF showed good negative correlations with Shwachman scores; thus those CF patients with the most advanced lung disease had the highest moment ratios and vice versa. Moment analysis of MBNW has promise as a means of quantifying lung function in young children, since the method is noninvasive, low in inherent variability, requires only quiet breathing, and has the sensitivity required to detect rather mild ventilation inhomogeneity. PMID- 4030575 TI - Increased gravitational stress does not alter maximum expiratory flow. AB - We measured maximum expiratory flow-volume (MEFV) curves in six seated subjects during normal (+1 Gz) and increased (+2 and +3 Gz) gravitational stress. Full MEFV curves, initiated at total lung capacity, were recorded, as were partial MEFV curves, initiated at approximately 60% of the vital capacity. Data were acquired in all subjects breathing air at +1 and +2 Gz; results were available for three subjects breathing 80% He-20% O2 at +1 and +2 Gz, and in two subjects, results were obtained at +3 Gz. Changes in gravitational stress were not associated with changes of either full or partial MEFV curves. The known increase in differences of regional lung volume and recoil caused by increased gravitational stress did not influence maximum expiratory flow. Though increased gravitational stress probably changed regional emptying sequences little during full MEFV maneuvers, substantial changes of emptying sequence were expected during partial maneuvers. It is possible that such changes in emptying sequence occurred but were not associated with changes in maximum flow because the latter was determined by choking in central airways common to all regions. PMID- 4030576 TI - Pressure-flow relationships of endotracheal tubes during high-frequency ventilation. AB - We studied the pressure-flow relationships of various endotracheal tubes (ETT) at frequencies (f) and tidal volumes (VT) in the range used for high-frequency ventilation (HFV) (f: 2-32 Hz, VT: 15-100 ml). Sinusoidal flows were applied to ETT inserted into a rigid bottle or into the tracheae of three anesthetized paralyzed dogs, while pressure fluctuations were measured both proximal and distal to the ETT. The pressure drops in the ETT were nonlinearly related to the peak flow rate and were VT dependent, suggesting that turbulent frictional head loss and convective acceleration were important. The pressure drops measured in vitro were found to be in good agreement with the predictions of a nonlinear oscillatory pressure-flow equation (derived herein), which incorporate the effects of turbulent frictional losses, convective acceleration, inertance, and compliance. The pressure drops measured in situ were 30-50% higher than with the corresponding f-VT combinations in vitro. Possible explanations of these differences are junctional losses at the tip of the ETT or the nonrigid character of the trachea. PMID- 4030577 TI - Promethazine or DPPD pretreatment attenuates oleic acid-induced injury in isolated canine lungs. AB - Oleic acid causes pulmonary edema by increasing capillary endothelial permeability, although the mechanism of this action is uncertain. We tested the hypothesis that the damage is an oxidant injury initiated by oleic acid, using isolated blood-perfused canine lung lobes. The lobes were dilated with papaverine and perfused in zone III with a constant airway pressure of 3 cmH2O. Changes in isogravimetric capillary pressure (Pc,i) and capillary filtration coefficient (Kf,C) were used as indices of alterations in microvascular permeability in lungs treated with silicone fluid (n = 3), oleic acid (n = 11), oleic acid after pretreatment with the antioxidants promethazine HCl (n = 11) or N,N'-diphenyl-p phenylenediamine (DPPD; n = 4), or oleic acid following pretreatment with methylprednisolone (n = 4). Kf,C averaged 0.21 +/- 0.02 ml X min-1 X cmH2O-1 X 100 g-1 in control and increased to 0.55 +/- 0.05 and 0.47 +/- 0.05 when measured 20 and 180 min after the administration of oleic acid. When oleic acid was infused into lungs pretreated with promethazine, Kf,C increased to only 0.38 +/- 0.05 ml X min-1 X cmH2O-1 X 100 g-1 after 20 min and had returned to control levels by 180 min. Pretreatment with DPPD, but not methylprednisolone, similarly attenuated the increase in Kf,C following oleic acid. Silicone fluid had no effect on Kf,C. That oleic acid increases vascular permeability was also evidenced by a fall (P less than 0.05) in Pc,i from control when measured at 180 min in every group.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4030578 TI - Mechanical output following muscle stretch in forearm supination against inertial loads. AB - Muscle stretch enhances force produced in both single fibers and voluntarily activated human muscle. This study determined how initial conditions of muscle stretch (and associated eccentric work), muscle length, and load inertia contributed to human concentric muscular output during maximal voluntary forearm supination. Outputs of angular velocity and concentric work over specific displacements and times of motion were calculated. Multiple regression analysis was performed using these outputs and initial conditions as dependent and independent variables, respectively. Initial conditions were shown to be significant and systematic determinants of muscle output in concentric contraction. Evidence of a temporary shift in the force-velocity curve was found and discussed regarding its beneficial contribution to load movement. Greater benefit was considered to be due to the fact that muscle stretch allows time for achievement of maximal muscular recruitment prior to concentric contraction. This produces large forces at the onset of the concentric phase, in comparison with contractions starting from rest. These findings were discussed with regard to both single- and multi-segment movement patterns. PMID- 4030579 TI - Treadmill vs. floor walking: kinematics, electromyogram, and heart rate. AB - To identify the degree of difference between treadmill and floor walking, kinematic, electromyographic (EMG), and heart rate measurements were recorded in seven normal female subjects during walking at three speeds on the treadmill and on the floor. During treadmill walking, subjects tended to use a faster cadence and shorter stride length than during floor walking. In addition the displacements of the head, hip, and ankle in the sagittal plane showed statistically significant differences between floor and treadmill walking. Average EMG activity was usually greater on the treadmill than on the floor; however, this difference was only significant for the quadriceps. Heart rate was significantly higher during fast treadmill walking than floor walking. In general, treadmill walking was not found to differ markedly from floor walking in kinematic measurements or EMG patterns. PMID- 4030580 TI - Circulatory adaptation to bimodal respiration in the dipnoan lungfish. AB - In the dipnoan lungfish, Protopterus aethiopicus, P. annectens, and Lepidosiren paradoxa, the ductus is a short powerful muscular vascular trunk forming a channel for communication between the systemic and pulmonary circulations. In structure, the dipnoan ductus is very similar to the ductus arteriosus (Botalli) in the mammal. Innervation is abundant, consisting of myelinated and nonmyelinated nerve fibers issuing, at least in part, from the vagus. Neurons are present in the adventitia, and numerous nerve profiles, filled with small agranular vesicles, are closely associated with the myocytes, suggesting strong cholinergic control. Perfusion of the ductus in vitro using hypoxic saline causes it to dilate; conversely it is constricted by alpha-agonists. Dopamine and prostaglandin E2 are potent dilators, whereas the beta-agonist, isoproterenol, and acetylcholine are less powerful. A vasomotor segment has been identified on the pulmonary artery (PAVS) close to its junction with the ductus. Its location and structure are similar to the corresponding segment in amphibians and reptiles. It is innervated by endings filled with small clear vesicles. Granular vesicle cells are also present within the adventitia. The PAVS is constricted by acetylcholine. As in amphibians, alpha-agonists and hypoxic saline are without vasomotor effects. Based on the anatomic and physiological observations, a concept of cyclic perfusion of the gas exchangers in Dipnoi is proposed. During the alternation between air breathing (emersion) and apneic phases (immersion), the pattern of the circulation in the lungfish oscillates between that of a tetrapod and a fish. PMID- 4030581 TI - Mechanical aspects of chest wall distortion. AB - During passive inflation of the respiratory system, the rib cage (RC) expands because the pressure applied to it [approximately equal to abdominal pressure (Pab)] increases. Similar Pab-tidal volume (VT) relationships between passive and spontaneous inspirations would occur only if 1) Pab acts on RC equally in the two situations (no distortion) or 2) the extradiaphragmatic inspiratory muscles expand RC, compensating for distortion. In anesthetized adult rats and in sleeping human infants the passive relationships between VT and Pab or abdomen motion (AB) were constructed by occluding the airways during expiration. For a given Pab (or AB) in active breathing VT averaged 55% (rats) and 49% (infants) of the passive volume change. With phrenic stimulation in rats VT was only slightly less than during spontaneous breathing, indicating that, in the latter case, the respiratory system was essentially driven only by the diaphragm. In both species occasional breaths with large RC expansion occurred, and VT was then equal to or larger than the passive volume at iso-Pab. We conclude that 1) RC distortion decreases VT to approximately half of the passive value and 2) being on the relaxation curve reflects "compensated" distortion and not absence of it. PMID- 4030582 TI - Measurement of bronchial arterial blood flow and bronchovascular resistance in sheep. AB - We studied the bronchial arterial blood flow (Qbr) and bronchial vascular resistance (BVR) in sheep prepared with carotid-bronchial artery shunt. Nine adult sheep were anesthetized, and through a left thoracotomy a heparinized Teflon-tipped Silastic catheter was introduced into the bronchial artery. The other end of the catheter was brought out through the chest wall and through a neck incision was introduced into the carotid artery. A reservoir filled with warm heparinized blood was connected to this shunt. The height of blood column in the reservoir was kept constant at 150 cm by adding more blood. Qbr was measured, after interrupting the carotid-bronchial artery flow, by the changes in the reservoir volume. The bronchial arterial back pressure (Pbr) was measured through the shunt when both carotid-bronchial artery and reservoir Qbr had been temporarily interrupted. The mean Qbr was 34.1 +/- 2.9 (SE) ml/min, Pbr = 17.5 +/ 3.3 cmH2O, BVR = 3.9 +/- 0.5 cmH2O X ml-1 X min, mean pulmonary arterial pressure = 21.5 +/- 3.6 cmH2O, and pulmonary capillary wedge pressure (Ppcw) = 14.3 +/- 3.7 cmH2O. We further studied the effect of increased left atrial pressure on these parameters by inflating a balloon in the left atrium. The left atrial balloon inflation increased Ppcw to 25.3 +/- 3.1 cmH2O, Qbr decreased to 21.8 +/- 2.4 ml/min (P less than 0.05), and BVR increased to 5.5 +/- 1.0 cmH2O.ml 1.min (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4030583 TI - Torque-velocity characteristics and muscle fiber type in human vastus lateralis. AB - The relationship between torque-velocity characteristics of the knee extensors during isokinetic contractions and muscle fiber type of the vastus lateralis, determined from two muscle biopsy samples, was investigated in 12 male and 18 female subjects. Peak torque, corrected for the effect of gravity and impact artifact, was classified as corrected peak torque. The torque measured 30 degrees from full extension and, corrected for gravity, was classified as corrected torque at 30 degrees. No significant correlations were found between the percentage of fast-twitch fibers (%FT) or the relative area of FT fibers (%FTA) and corrected peak torque values for any of the velocities tested or the knee angles where corrected peak torques were measured. However, significant inverse relationships were determined for corrected torque at 30 degrees at all but the fastest velocity (270 degrees/s) and both %FT and %FTA for the male subjects. These results reveal that muscle fiber type of the vastus lateralis, based on duplicate muscle samples, is not related to the peak torque actually generated by the knee extensors but may influence the shape of the torque output for maximal contractions sustained over the entire range of motion. PMID- 4030584 TI - Endurance training in humans: aerobic capacity and structure of skeletal muscle. AB - The adaptation of muscle structure, power output, and mass-specific rate of maximal O2 consumption (VO2max/Mb) with endurance training on bicycle ergometers was studied for five male and five female subjects. Biopsies of vastus lateralis muscle and VO2max determinations were made at the start and end of 6 wk of training. The power output maintained on the ergometer daily for 30 min was adjusted to achieve a heart rate exceeding 85% of the maximum for two-thirds of the training session. It is proposed that the observed preferential proliferation of subsarcolemmal vs. interfibrillar mitochondria and the increase in intracellular lipid deposits are two possible mechanisms by which muscle cells adapt to an increased use of fat as a fuel. The relative increase of VO2max/Mb (14%) with training was found to be smaller by more than twofold than the relative increase in maximal maintained power (33%) and the relative change in the volume density of total mitochondria (+40%). However, the calculated VO2 required at an efficiency of 0.25 to produce the observed mass-specific increase in maximal maintained power matched the actual increase in VO2max/Mb (8.0 and 6.5 ml O2 X min-1 X kg-1, respectively). These results indicate that despite disparate relative changes the absolute change in aerobic capacity at the local level (maintained power) can account for the increase in aerobic capacity observed at the general level (VO2max). PMID- 4030585 TI - Airway resistance and respiratory muscle function in snorers during NREM sleep. AB - The effect of non-rapid-eye-movement (NREM) sleep on total pulmonary resistance (RL) and respiratory muscle function was determined in four snorers and four nonsnorers. RL at peak flow increased progressively from wakefulness through the stages of NREM sleep in all snorers (3.7 +/- 0.4 vs. 13.0 +/- 4.0 cmH2O X 0.1(-1) X s) and nonsnorers (4.8 +/- 0.4 vs. 7.5 +/- 1.1 cmH2O X 1(-1) X s). Snorers developed inspiratory flow limitation and progressive increase in RL within a breath. The increased RL placed an increased resistive load on the inspiratory muscles, increasing the pressure-time product for the diaphragm between wakefulness and NREM sleep. Tidal volume and minute ventilation decreased in all subjects. The three snorers who showed the greatest increase in within-breath RL demonstrated an increase in the contribution of the lateral rib cage to tidal volume, a contraction of the abdominal muscles during a substantial part of expiration, and an abrupt relaxation of abdominal muscles at the onset of inspiration. We concluded that the magnitude of increase in RL leads to dynamic compression of the upper airway during inspiration, marked distortion of the rib cage, recruitment of the intercostal muscles, and an increased contribution of expiratory muscles to inspiration. This increased RL acts as an internal resistive load that probably contributes to hypoventilation and CO2 retention in NREM sleep. PMID- 4030586 TI - Effect of beta-adrenoceptor blockade on H+ and K+ flux in exercising humans. AB - The effect of beta-adrenoceptor blockade (beta B) on muscle release and uptake of H+ and K+ in humans during maximal exercise has been investigated. Eight volunteers cycled intermittently at power outputs corresponding to 100% of maximal O2 uptake. Prior to exercise either propranolol (beta B) or saline (control) was infused into the femoral vein. Arterial and femoral venous blood samples were drawn at rest, during exercise, and during 30-min recovery. Peak arterial blood values for K+, lactic acid (LA), and base deficit (BD) (mean +/- SE) were respectively 5.5 +/- 0.1, 9.5 +/- 0.6, and 11.7 +/- 0.9 mmol/l during beta B and 5.1 +/- 0.1, 8.3 +/- 0.6, and 10.3 +/- 1.0 for control (P less than 0.05). The release of K+ from the working leg did not differ between treatments during exercise, but K+ uptake during late recovery (5-30 min) was slightly lower during beta B. Thus the higher arterial K+ levels during exercise (beta B) cannot be attributed to greater release by active muscle but are likely due to decreased K+ uptake by noncontracting muscle. Arterial-femoral venous differences for LA and BD did not differ significantly between treatments. Additionally LA exchange across the leg was similar to H+ exchange (arterial-femoral venous differences for BD) under all conditions. During early recovery (1-5 min), regardless of experimental treatment, BD levels iin arterial blood were higher than LA (P less than 0.05). These elevated BD levels may be due to unequal removal rates between LA and H+ equivalents by nonexercised tissue.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4030587 TI - Differences in endogenous pyrogen fevers induced by iv and icv routes in rabbits. AB - We have compared the characteristics of fevers produced by endogenous pyrogen administered by the intravenous (iv) and by the intracerebroventricular (icv) routes in conscious rabbits. Fevers induced by the intracerebroventricular route have a longer latency to onset, a less steep rise in body temperature, and a longer time to peak elevation in body temperature than do fevers induced by the intravenous route. Furthermore, a dose of indomethacin (2 mg/kg) administered intravenously, which is effective in markedly attenuating fevers produced by the intravenous route, was completely without effect on fevers induced by the intracerebroventricular route. On the other hand, when indomethacin (500 micrograms) was infused intracerebroventricularly, it markedly reduced fevers induced by the subsequent injection of endogenous pyrogen into the contralateral cerebral ventricle, but such pretreatment had little effect on fevers elicited by intravenous injections of endogenous pyrogen. It is concluded that the sites of action of endogenous pyrogen in response to intravenous injections of pyrogen are different from those responding to intracerebroventricular injections of pyrogen and that this is manifest in several distinct differences in the characteristics of the two fevers. These results indicate that the intracerebroventricular model of fever production is not appropriate for the study of the normal pathogenesis of fever. PMID- 4030588 TI - Blood viscosity responses to maximal exercise in endurance-trained and sedentary female subjects. AB - To assess whether the rheological properties of blood might be altered by exercise, we measured whole blood viscosity, plasma viscosity, and its components in healthy female subjects before, immediately after, and 1 h after maximal upright exercise using the Bruce graded exercise protocol. Forty-seven female subjects (15 sedentary, 14 who ran 5-15 miles/wk, and 18 who ran greater than 50 miles/wk), ages 18-43 yr, were evaluated. Whole blood viscosity, measured with a cone and plate viscometer, increased an average of 12.6% with exercise. The increase was greater than can be attributed to the observed 8.9% increase in hematocrit alone due to a coincident increase in plasma protein concentration. However, plasma viscosity did not rise to the degree expected, likely due to a disproportionate observed loss of fibrinogen from the protein pool. These changes were independent of conditioning level or aerobic capacity. In this cross sectional study, there appears to be no adaptive adjustment in females to physical conditioning that results in changes in blood viscosity. PMID- 4030589 TI - Pulmonary and cardiovascular changes in hyperreactive rats from citric acid aerosols. AB - Administration of aerosols of citric acid to anesthetized spontaneously breathing hyperreactive rats produced reversible increases in respiratory rate (f) and pleural pressure (Ppl) accompanied by hypotension and bradycardia. In contrast, Fischer rats, which do not have bronchial hyperreactivity, failed to respond to citric acid aerosols. The effects of various treatments on citric acid-induced changes in f, Ppl and blood pressure were studied. Vagotomy, cromolyn sodium (1 and 10 mg/kg iv), mecamylamine, (2 mg/kg iv), FPL-55712 (3 mg/kg iv), and BW 755C (10 mg/kg iv) inhibited markedly the responses to citric acid, whereas atropine (2 mg/kg iv) produced weak inhibition. Methysergide (1 mg/kg iv), indomethacin (1 mg/kg iv), and a prostanoid antagonist, L-640,035, (5 mg/kg iv) were completely ineffective. The results suggest that citric acid-induced bronchoconstriction in hyperreactive rats may be reflex mediated and that leukotrienes may be involved in the response. PMID- 4030590 TI - Mechanical impedance as determinant of inspiratory neural drive during exercise in humans. AB - Five healthy males exercised progressively with small 2-min increments in work load. We measured inspiratory drive (occlusion pressure, P0.1), pulmonary resistance (RL), dynamic pulmonary compliance (Cdyn), transdiaphragmatic pressure (Pdi), and diaphragmatic electromyogram (EMGdi). Minute ventilation (VE), mean inspiratory flow rate (VT/TI), and P0.1 all increased exponentially with increased work load, but P0.1 increased at a faster rate than did VT/TI or VE. Thus effective impedance (P0.1/VT/TI) rose throughout exercise. The increasing P0.1 was mostly due to augmented Pdi and coincided with increased EMGdi during this initial portion of inspiration. We found no consistent change in RL or Cdyn throughout exercise. With He breathing (80% He-20% O2), RL was reduced at all work loads; P0.1 fell in comparison with air-breathing values and VE, VT, and VT/TI rose in moderate and heavy work; and P0.1/VT/TI was unchanged with increasing exercise loads. Step reductions in gas density at a constant work load of any intensity showed an immediate reduction in the rate of rise of EMGdi and Pdi followed by increased VT/TI, breathing frequency, and hypocapnia. These changes were maintained during prolonged periods of unloading and were immediately reversible on return to air breathing. These data are consistent with the existence of a reflex effect on the magnitude of inspiratory neural drive during exercise that is sensitive to the load presented by the normal mechanical time constant of the respiratory system. This "load" is a significant determinant of the hyperpneic response and thus of the maintenance of normocapnia during exercise. PMID- 4030591 TI - Function of mature coronary collateral vessels and cardiac performance in the exercising dog. AB - Formation of extensive collateral vessels after chronic constriction of a coronary artery in dogs can provide for similar increases in blood flow to native and collateralized regions of myocardium during exertion. Previous investigations have not compared myocardial blood flow and cardiac functional responses during exercise in constricted and nonconstricted (sham) animals. Thus we evaluated left ventricular performance and myocardial blood flow at rest and during mild, moderate, and severe exertion in sham-operated dogs and in dogs 2-3 mo after placement of an Ameroid occluder around the proximal left circumflex artery. Changes in double product, maximal left ventricular dP/dt, and pressure-work index were similar in both groups for each level of exertion. Despite similar increases in estimated myocardial O2 demand and similar diastolic perfusion pressures, average transmural myocardial blood flow increased less in the constrictor animals, particularly during severe exercise (2.74 +/- 0.22 vs. 1.45 +/- 0.29 ml X min-1 X g-1). The smaller increases in blood flow occurred equally in native and collateralized regions as well as in the papillary muscles and boundary areas between the native and collateralized regions. The differences in flow in the native and collateralized regions were uniform across the wall of the myocardium. We also observed smaller increases in stroke volume and cardiac output in the constrictor group, disparities which increased with increasing exertion (stroke volume, severe exercise = 0.92 +/- 0.13 vs. 0.53 +/- 0.09 ml/kg). We postulate that myocardial active hyperemia is limited either because the coronary vessels remaining after chronic circumflex occlusion cannot dilate sufficiently or that there is inappropriate active vasoconstriction during severe exertion.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4030592 TI - Human esophageal pressures and chest wall configuration in upright and head-down posture. AB - Pressures were measured at two levels in the esophagus in 14 young healthy subjects performing slow inspiratory and expiratory vital capacity (VC) maneuvers in upright and head-down posture (180 degrees body tilt). In both postures, a gravitational pressure gradient was found, which increased very slightly with decreasing lung volumes (0.006 cmH2O X % VC-1 X cm descent-1) except for upright expiratory curves above 60% VC. The expiratory pressure gradient tended to be larger in head-down than in upright posture; however, during inspiration the opposite was true. In both postures the pressure change between 100 and 20% VC was smaller in the uppermost zone, which is consistent with the smaller changes in alveolar expansion in this zone. Also, in seven of the subjects, changes in cross-sectional area of the middle and lower part of the rib cage (HRC and LRC) and of the abdomen (ABD) were measured by respiratory inductive plethysmography in upright and head-down posture. The ratio of HRC motion to LRC motion was constant throughout the VC and did not change with posture, yet the ratio of ABD motion to mean RC motion changed with overall volume and was also larger in head down than in upright posture. In conclusion, the changes in esophageal pressure gradient during slow VC maneuvers in head-down vs. upright posture were not related to (and thus not caused by) changes in chest wall configuration. PMID- 4030593 TI - Acclimation of rats following stepwise or direct exposure to heat. AB - The physiological changes in male rats during acclimation were studied following direct or stepwise exposure to heat (32.5 degrees C) in a controlled-environment room. The animals were exposed to each temperature for 10 days beginning at 24.5 degrees C and returning to 24.5 degrees C in the reverse order of initial exposure. Relative humidity of 50 +/- 2% and a 12-h light-dark photoperiod (light from 0900 to 2100 h) were maintained. Physiological changes in metabolic rate (MR), evaporative water loss (EWL), plasma corticosterone, body water turnover, and food and water intake were measured. The results indicate a significantly (P less than 0.001) elevated plasma corticosterone and MR in rats exposed directly to heat from control temperature (24.5 degrees C) but not in those animals exposed stepwise via 29.0 degrees C. All kinetic parameters of water pool changed (P less than 0.01) on direct exposure to heat, whereas rats exposed in a stepwise manner increased only pool turnover. In addition, exposure to experimental temperatures resulted in reduced (P less than 0.05) relative food intake and increased (P less than 0.05) water intake. Compared with the control condition of 24.5 degrees C, EWL was significantly (P less than 0.05) elevated when the animals were exposed either directly or in a stepwise fashion to 32.5 degrees C. These data suggest that the response to elevated temperatures is influenced by the temperature to which the rat is acclimated. PMID- 4030594 TI - Effect of thermal history on the rat's response to varying environmental temperature. AB - After acclimating individually housed male rats to temperatures of either 24.5 +/ 0.1 or 29.2 +/- 0.1 degrees C for 14 days, randomly paired animals from each group were acutely exposed (3 h) in series to experimental temperatures between 18.0 and 34.5 degrees C in a controlled environment room. Relative humidity of 50 +/- 0.3% and a 12-h light-dark photoperiod (light from 0900 to 2100 h) were maintained. Metabolic rate (MR) and evaporative water loss (EWL) were-measured using an open-flow system; thermistors were used to measure the rectal (Tre) and tail skin (Tts) temperatures. MR was relatively constant over a temperature range of 22.2 to 27.0 degrees C for rats acclimated to 24.5 degrees C and 20.0 to 29.2 degrees C for rats acclimated to 29.2 degrees C. Above and below these ranges, MR for both groups was significantly (P less than 0.05) elevated. At their respective acclimation temperatures, the absolute Tre and Tts of 29.2 degrees C rats were maintained at an elevated level compared with 24.5 degrees C rats. Although EWL for both groups was relatively constant between 18.0 and 27.0 degrees C, 24.5 degrees C rats displayed higher EWL changes at most environmental temperatures above 27.0 degrees C. At 34.5 degrees C, 29.2 degrees C rats dissipated 26% more metabolic heat by evaporation compared with 24.5 degrees C rats. These data suggest that acclimation temperatures of rats affected the thermoneutral zone and alter the set-point temperature around which thermal responses are regulated. PMID- 4030595 TI - Effect of alcohol on apnea reflexes in young lambs. AB - This study examined the effect of alcohol on two apnea reflexes considered to be protective mechanisms through which animals and humans preserve vital functions while they are submerged in water. The laryngeal chemoreflex and the trigeminal diving reflex were studied in unanesthetized 1- to 3-wk-old lambs. Reflex stimulation resulted in reduced ventilation or apnea, bradycardia, hypertension, and blood flow redistribution in the dive pattern. After alcohol, reflex stimulation resulted in increased apnea response, preserved blood flow redistribution, but less hypertension. The onset of regular breathing following laryngeal water stimulation was significantly delayed, after alcohol, and mechanical ventilation was used in three lambs to terminate the prolonged poststimulus apnea. Airway occlusion pressure, an index of neuromuscular inspiratory drive, decreased significantly after alcohol. The study demonstrates a potent effect of alcohol on apnea reflex responses. The effect of alcohol on respiratory drive and on the apnea reflex response should be considered when humans ingest alcohol, in particular by those participating in water sports. PMID- 4030596 TI - Effect of distortion on the mechanical properties of newborn piglet lung. AB - During breathing the relatively high chest wall-to-lung compliance ratio of the newborn favors distortion of the respiratory system. In this study we have examined the effect of lung deformation, generated by a hydrostatic pleural surface pressure gradient, on the static (Cstat) and dynamic (Cdyn) compliance of the isolated newborn piglet lung. Seven lungs from piglets 2-7 days old have been studied in a saline-filled plethysmograph. Static pressure-volume (PV) curves were obtained by changing the volume a known amount and measuring the corresponding changes in transpulmonary pressure. Dynamic PV curves were obtained by ventilating the lung at a fixed pressure and at 20 cycles/min. These experiments were repeated in an air plethysmograph on the undeformed lung. Lung volume history was standardized prior to each maneuver by three inflations to 20 25 cmH2O. Lung collapse was avoided by applying an end-expiratory load equal to the transpulmonary pressure at functional residual capacity. Cstat was not significantly different between the deformed and undeformed lung (P greater than 0.05). Cdyn was less than Cstat in both cases (P less than 0.025) and was reduced further by deformation (P less than 0.05). We conclude that 1) peripheral airway obstruction or the viscoelastic properties of the piglet lung, or both, decrease Cdyn, and 2) deformation increases the external (PV) respiratory work by further decreasing Cdyn. PMID- 4030597 TI - Respiratory changes in nasal muscle length. AB - Respiratory changes in alae nasi muscle length were recorded using sonomicrometry in pentobarbital sodium-anesthetized tracheostomized dogs spontaneously breathing 100% O2. Piezoelectric crystals were inserted via small incisions into the alae nasi of 11 animals, and bipolar fine-wire electrodes were inserted contralaterally in nine of the same animals. The alae nasi shortened during inspiration in all animals. The mean amount of shortening was 1.33 +/- 0.22% of resting length (LR), and the mean velocity of shortening during the first 200 ms was 4.60 +/- 0.69% LR/S. The onset of alae nasi shortening preceded inspiratory flow by 77 +/- 18 ms (P less than 0.002), at which time both alae nasi shortening and the moving average of electromyographic (EMG) activity had reached approximately one-third of their peak values. In contrast, there was a relative delay in alae nasi relaxation relative to the decay of alae nasi EMG at the end of expiration. Single-breath airway occlusions at end expiration changed the normally rounded pattern of alae nasi shortening and moving average EMG to a late inspiratory peaking pattern; both total shortening and EMG were increased by similar amounts. The onset of vagally mediated volume-related inhibition of alae nasi shortening occurred synchronously with the onset of inhibition of alae nasi EMG; both occurred at lung volumes substantially below tidal volume. These results indicate that the pattern of inspiratory shortening of this nasal dilating muscle is reflected closely in the pattern of EMG activity and that vagal afferents cause substantial inhibition of alae nasi inspiratory shortening. PMID- 4030598 TI - Pressor reflex evoked by muscular contraction: contributions by neuraxis levels. AB - The pressor reflex evoked by muscular contraction (exercise pressor reflex) is one important model of cardiovascular adjustments during static exercise. The central nervous system (CNS) structures mediating this reflex have remained largely obscure. Therefore, we examined the contribution of selected levels of the neuraxis in mediating the pressor reflex evoked by muscular contraction from stimulation of ventral roots. Decerebrate cats exhibited larger pressor reflexes than those found in intact alpha-chloralose-anesthetized cats, a difference more apparent at low (5 Hz or repeated twitch) rather than at high (50 Hz or tetanic) stimulus frequencies. Although a depressor response to 5-Hz stimulation was observed in the intact anesthetized cats, it appeared to be primarily due to anesthetic level, since a depressor response was not observed in decerebrate animals (nonanesthetized). Cerebellectomy produced no changes in the reflexes of the decerebrate animal. Further transection of the neuraxis (caudal to the midcollicular level) attenuated the exercise pressor reflex. The spinal cat demonstrated slight evidence of exercise pressor reflex activity. These results provide clarification as to representation of this pressor reflex within the CNS and establish the reflex's characteristics at several levels of neuraxis integration. PMID- 4030599 TI - Effect of body orientation on regional lung expansion: a computed tomographic approach. AB - The Dynamic Spatial Reconstructor (DSR) was used to study in vivo lung geometry and function. By replacing the lungs of three dogs with potato flakes and ping pong balls of known air content and scanning these realistic phantoms in the DSR we have estimated accuracy of lung density to be within 7% and have demonstrated a high (+/- 3%) internal consistency (relative density within dogs). Change in total lung air content (y) as calculated from DSR volume imaging of anesthetized dogs matched the known inflation steps (x) to within 7% [range was 1-7% with a mean of 3 +/- 0.5% (SE)]. A gradient of decreasing percent lung air content was measured in the ventral-dorsal direction at functional residual capacity (FRC) in the supine body posture (y = 3.29% air content/cm lung height + 46.48% air content; r = 0.90). Regional lung air content change with lung inflation was greatest in the dependent lung regions. In contrast, regional lung air content at FRC was approximately uniform along the ventral-dorsal direction with the dog in the prone posture and was 66 +/- 0.6% (SE). Ventral-dorsal gradients in lung air content measured within an isogravimetric plane of the dogs in the left or right lateral body posture suggest that regional differences in lung air content cannot be explained solely on the basis of a direct gravitational effect on the lung. Evidence is presented to suggest a possible major role of the intrathoracic position of the mediastinal contents in determining these lung air content distributions. PMID- 4030601 TI - Total respiratory input and transfer impedances in humans. AB - Total respiratory input (Zrs,in) and transfer (Zrs,tr) impedances were obtained from 4 to 30 Hz in 10 healthy males by simultaneously measuring mouth and chest flow while applying pseudo-random pressure variations at the mouth. Compared with Zrs,in, the real part of Zrs,tr was larger up to 10 Hz but exhibited a much stronger negative frequency dependence. The imaginary part was larger at all frequencies, with a resonant frequency (fn) at 6.0 +/- 0.8 Hz compared with 8.2 +/- 2.9 Hz for Zrs,in. The two impedances were analyzed with a model featuring airway resistance and inertance, alveolar gas compressibility, and tissue resistance, inertance, and compliance. A good fit was generally obtained but, in most cases, with a different partitioning of resistance between airway and tissue for Zrs,in and Zrs,tr. The data were also used to compute separately airway and tissue (Zt) impedances. In most subjects Zt could not be properly fitted with a simple resistance-inertance-compliance unit and was consistent with a slow (fn = 7.4 +/- 2.3 Hz) overdamped compartment in parallel with a fast (fn = 37.1 +/- 5.6 Hz) underdamped one. PMID- 4030600 TI - Effect of body orientation on regional lung expansion in dog and sloth. AB - Recent studies (E.A. Hoffman, J. Appl. Physiol. 59: 468-480, 1985) using fast multisliced X-ray computed tomography have demonstrated a ventral-dorsal gradient of fractional lung air content (3.29% air/cm lung height) in supine dogs and an essentially uniform ventral-dorsal air content distribution in the prone dogs [mean = 66 +/- 0.6% (SE) air content]. Since the prone orientation is the dog's normal body posture, we sought to study an animal whose normal body posture was "opposite" to that of the dog. Four two-toed sloths were scanned in the Dynamic Spatial Reconstructor in the prone and supine postures. A supine fractional air content gradient was demonstrated with a regression equation of y = 2.09x + 74.3 (r = 0.92), where y is percent air content and x is vertical height in the lung, and ventral-dorsal air content distribution in the prone posture was uniform with a mean of 85 +/- 0.4% (SE) air content. The low functional residual capacity lung density in the sloth was attributable to unusually large alveoli. The mean heart volume-to-body weight ratio in the dogs was 16.4 +/- 0.6 (SE) ml/kg and that in the sloth was 7.3 +/- 0.4 (SE) ml/kg. Mean lung volume-to-body weight ratios for dogs and sloths were 57 +/- 7 (SE) and 89 +/- 6 ml/kg, respectively. Of particular interest was the fact that large changes in prone vs. supine rib cage and diaphragm geometry previously found in dogs did not occur in sloths, though significant alterations of ventral and dorsal lung geometry prone vs. supine were demonstrated, and lung shape changes in both dog and sloth are attributable to shifts in the intrathoracic position of mediastinal structures. PMID- 4030602 TI - Location of flow-limiting segments via airway catheters near residual volume in humans. AB - Previous studies have demonstrated sites of flow limitation in the central airways of dogs and humans. At low lung volumes, however, during a forced expiration, it is not clear whether flow-limiting segments (FLS) move into the lung periphery. Using intrabronchial lateral pressure catheters, we located FLS in human subjects at all lung volumes between functional residual capacity (FRC) and residual volume (RV). Three individuals with severe intracranial hemorrhage maintained on ventilators were studied. Partial maximal flow-volume curves were generated from 1 liter above FRC to RV by lowering downstream pressure and using the interrupter technique. Sites of FLS were defined as the most downstream points where lateral pressure did not change with driving pressure. FLS were found in all subjects in the central airways. In one subject, FLS moved from segmental bronchi to the first subsegmental bronchus as RV was approached but not beyond. In the other two subjects, FLS remained fixed in location at all measured lung volumes. At constant volume, multiple FLS were located, all in parallel, e.g., fixed in left upper, left lower, and right middle lobar bronchi. In conclusion, sites of flow limitation remain in the central airways as lung volume approaches RV. FLS may move peripherally within the central airways but not beyond proximal subsegmental bronchi. PMID- 4030603 TI - Enhancement of particle deposition by flow-limiting segments in humans. AB - Severe chronic obstructive pulmonary disease is associated with central deposition of inhaled aerosols. This pattern may be due to functional narrowing of the large airways during expiration at flow-limiting segments (FLS). Using a gamma camera and 2.5-micron particles, we compared the pattern of aerosol deposition following quiet breathing with that after a controlled forced expiration (cough) when FLS are known to form in central airways. Lung size measurement by 133Xe allowed construction of regions of interest over the central airways and lung periphery. Deposition in these regions was normalized for area and lung thickness and expressed as a central-to-peripheral (C/P) ratio. In addition, using right-angle light scattering, the fraction of inhaled particles deposited with each breath (DF) was determined. During control studies, airflow and tidal volume were continuously monitored to insure that tidal loops were well below the maximum expiratory flow-volume (MEFV) curve. To create dynamic compression, cough was used to generate a partial MEFV curve, while inspiratory flow, tidal volume, and functional residual capacity were maintained close to quiet breathing. With cough, C/P ratios increased markedly from 1.04 +/- 0.18 to 2.21 +/- 0.61 (P less than 0.01, n = 6). DF for the lung and airways did not significantly change (0.43 +/- 0.11 to 0.45 +/- 0.09, P = NS). The greater enhancement of regional deposition in the central airways with deposition unchanged over the whole lung demonstrates that, during cough, peripheral deposition is actually reduced when compared with quiet breathing. We conclude that dynamic compression at FLS can be an important factor in the central deposition of inhaled particles. PMID- 4030604 TI - Flow limitation, cough, and patterns of aerosol deposition in humans. AB - We studied deposition of radioactive monodisperse 1.5-micron aerosol in humans following inhalation during quiet breathing. Two groups were studied: normal, defined by tidal loops below the maximum expiratory flow-volume (MEFV) envelope [forced expiratory volume at 1 s at percent of forced vital capacity (FEV1%) 62 78]; and flow-limited, with tidal loops superimposed on MEFV relationship (FEV1% 21-57) and flow-limiting segments (FLS) known to exist in central airways. During simultaneous imaging with a gamma camera, fraction of inhaled aerosol deposited in the lung (DF) was determined by right-angle light scattering. With regions of interest defined by an equilibrium image of 133Xe, regional deposition was normalized for area and lung thickness and expressed as a central-to-peripheral (C/P) ratio. Deposition was uniform throughout the lung in normal subjects [C/P 1.02 +/- 0.07 (SD), n = 6]. In flow-limited group, central deposition predominated (C/P 1.98 +/- 0.64, n = 6, P less than 0.05). Tidal volume and inspiratory flow, forces thought to influence deposition during inspiration, were not different between groups. Spontaneous cough occurred in five flow-limited subjects during aerosol inhalation, with further increase in central deposition when compared with quiet breathing (C/P 1.85 +/- 0.60 to 2.69 +/- 0.600, P less than 0.01). During cough, tidal volume (ml) was reduced significantly (576 +/- 151 to 364 +/- 117, P less than 0.01) with no change in inspiratory flow (l/s) (1.37 +/- 0.23 to 1.38 +/- 0.40, P = NS). DF, however, was unaffected by cough (0.34 +/- 0.13 to 0.61 +/- 0.12, P = NS).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4030605 TI - Distortion of submerged dog lung lobes. AB - The conically shaped caudal lobes of dog lungs were submerged, tip downward in saline, and the lateral surfaces of the lobes were thereby exposed to a hydrostatic gradient in transpulmonary pressure. The force that was required to balance the buoyancy was applied through a clip attached to the tip of the lobe. The locations of metal markers implanted in the parenchyma and attached to the surface were tracked, and regional volume and the horizontal and vertical components of strain were obtained as functions of vertical position. An engineering analysis of the deformation is qualitatively consistent with the data, but the predicted strains are larger than the observed strains. From the experimental and analytical results, we conclude that, for this deformation, the regional volume-local transpulmonary pressure curve closely follows the pressure volume curve because negative horizontal strains nearly balance the positive vertical strain caused by the buoyancy force. PMID- 4030606 TI - Contractile properties of intercostal muscles and their functional significance. AB - To have some insight into the functional coupling between the parasternal intercostals (PS) and the diaphragm (DPM), we have examined the isometric contractile properties of bundles from canine PS and DPM muscles. Bundles of external (EXT) and internal (INT) interosseous intercostals were studied for comparison. In addition we have related sonometrically measured length of the intercostals in vivo at supine functional residual capacity (FRC) to in vitro optimal force-producing length (Lo). We found that 1) intercostal twitch speed is significantly faster than DPM, thus displacing their relative force-frequency curve to the right of that of the DPM; 2) the ascending limb of the active length tension curve of all intercostals lies below the DPM curve; i.e., at 85% Lo, PS force is 46% of maximal force (Po), whereas DPM force is still 87% Po; 3) for any given length change beyond Lo, all intercostals generate greater passive tension than the DPM; 4) Po is greater for the intercostals than the DPM; and 5) at supine FRC, both EXT and INT in dogs are nearly operating at Lo, whereas the PS are operating at a length greater than Lo. We conclude that 1) PS produce less force than DPM during breathing efforts involving low- (10-20 Hz) stimulation frequencies, but they generate more force than DPM when high- (greater than 50 Hz) stimulation frequencies are required; and 2) the pressure-generating ability of the PS is better preserved than that of the DPM with increases in lung volume.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4030607 TI - Changes in heart rate during breathing interrupted by recurrent apneas in humans. AB - Heart rate varies with breathing patterns, especially in sleep apnea. To assess the effects on heart rate of recurrent apneas interrupting tidal breathing, we studied five normal awake male subjects. These subjects voluntarily changed their breathing pattern from regular tidal breathing to tidal breathing interrupted by breath holding at end expiration. This recurrent apneic breathing pattern did not change mean heart rate but increased its variance significantly. In addition, the variations in heart rate formed a cyclic pattern of oscillation with a mean cycle length identical to both arterial O2 saturation (SaO2) (R = 0.95; P less than 0.01) and ventilation (R = 0.92; P less than 0.01). Cyclic changes in either SaO2 or ventilation reproduced the oscillatory patterns of heart rate seen with tidal breathing interrupted by multiple apneas, but the amplitude of the variance in heart rate was smaller. Finally, preventing the cyclic declines in SaO2 with supplemental O2 did not significantly alter the heart rate changes seen in tidal breathing interrupted by apneas. PMID- 4030608 TI - Transpulmonary passage of venous air emboli. AB - Twenty-seven paralyzed anesthetized dogs were embolized with venous air to determine the effectiveness of the pulmonary vasculature for bubble filtration or trapping. Air doses ranged from 0.05 to 0.40 ml X kg-1 X min-1 in 0.05-ml increments with ultrasonic Doppler monitors placed over arterial vessels to detect any microbubbles that crossed the lungs. Pulmonary vascular filtration of the venous air infusions was complete for the lower air doses ranging from 0.05 to 0.30 ml X kg-1 X min-1. When the air doses were increased to 0.35 ml X kg-1 X min-1, the filtration threshold was exceeded with arterial spillover of bubbles occurring in 50% of the animals and reaching 71% for 0.40 ml X kg-1 X min-1. Significant elevations were observed in pulmonary arterial pressure and pulmonary vascular resistance. Systemic blood pressure and cardiac output decreased, whereas left ventricular end-diastolic pressure remained unchanged. The results indicate that the filtration of venous bubbles by the pulmonary vasculature was complete when the air infusion rates were kept below a threshold value of 0.30 ml X kg-1 X min-1. PMID- 4030609 TI - Plasma volume changes in middle-aged male and female subjects during marathon running. AB - Circulatory fluid shifts were studied in middle-aged runners (6 males and 5 females, ages 32-58 yr) during a 42.2-km marathon race run in mild weather (dry bulb temperature = 17.5-20.4 degrees C). Running times for the subjects were 3:12 4:40 (mean values were 3:34 for males and 4:10 for females). Venous blood samples were taken without stasis in all subjects seated at rest before the start of the race and within 3 min of finishing; eight of the subjects also paused for samples at 6 and 27 km during the race. At 6 km, body weight loss averaged less than 1%, whereas plasma volume (PV) had decreased by 6.5% in male subjects and 8.6% in female subjects. By the end of the race, hypohydration had reached 3.2% in male subjects and 2.9% in female subjects, but PV in both groups remained stable. Sweat rates during the race averaged 545 and 429 g X m-2 X h-1 for male and female subjects, respectively, with ad lib. water intake replacing 21-72% of fluid loss. Increases in plasma protein concentration throughout the race reflected the observed initial decrease in PV. The interpretation of PV responses to exercise and/or hypohydration is critically dependent on selection of base line conditions; we were able to control for posture-exercise effects by treating the early exercise (6 km) sample as the base line for examining the effects of later fluid loss. Under these conditions, the vascular compartment resisted volume depletion. The ability to maintain stable PV can be explained in part by relationships among oncotic and hydrostatic pressures in the intra- and extravascular fluid compartments. PMID- 4030610 TI - Denervation of peripheral chemoreceptors decreases breathing movements in fetal sheep. AB - The role of the peripheral chemoreceptors in the control of fetal breathing movements has not been fully defined. To determine whether denervation of the peripheral chemoreceptors affects fetal breathing movements, we studied 14 chronically catheterized fetal sheep from 120 to 138 days of gestation. In seven fetuses the chemoreceptors were denervated by bilateral section of the vagus and carotid sinus nerves; in seven others, sham operations were performed. We compared several variables during two study periods: 0-5 and 6-13 days after operation. In the denervated fetuses there were significant decreases in the incidence and amplitude of fetal breathing movements during both study periods. There were no differences between the two groups in incidence of low-voltage electrocortical activity, arterial pH and blood gas tensions, fetal heart rate, mean arterial blood pressure, or duration of survival after operation or birth weight. We conclude that denervation of the peripheral chemoreceptors decreases fetal breathing movements. These results indicate that the peripheral chemoreceptors are active during fetal life and participate in the control of fetal breathing movements. PMID- 4030611 TI - Relation of blood-free to blood-inclusive postmortem lung water measurements in sheep. AB - Our purpose was to see if the postmortem weight ratio of extravascular lung water to blood-free dry lung (blood-free ratio) was related to similar ratios in blood inclusive lung and in blood. We developed linear regressions of blood-free ratio on ratios for blood-inclusive lung and blood together and for blood-inclusive lung alone for 73 sheep studied under 11 different protocols and for two subgroups of sheep, one with plasma space expansion and the other without expansion. The relation of ratios of blood-free to blood-inclusive lungs was different between the two subgroups. Although all regressions were highly correlated, the fits of the blood-free ratio on ratios for blood-inclusive lung and blood together were better than for blood-inclusive lung alone. The mean error of prediction of extravascular lung water for all sheep was significantly less for the regression of blood-free ratio on ratios for blood and blood inclusive lung together (11 g) than for blood-inclusive lung alone (18 g). This study shows that weights of lung homogenate and blood samples before and after simple oven drying can be used to provide accurate inexpensive estimates of postmortem extravascular lung water. PMID- 4030612 TI - Pleural liquid pressure in dogs measured using a rib capsule. AB - We have developed a minimally invasive method for measuring the hydrostatic pressure in the pleural space liquid. A liquid-filled capsule is bonded into a rib and a small hole is cut in the parietal pleura to allow direct communication between the liquid in the capsule and the pleural space. The pressure can be measured continuously by a strain gauge transducer connected to the capsule. The rib capsule does not distort the pleural space or require removal of intercostal muscle. Pneumothoraces are easily detected when they occur inadvertently on puncturing the parietal pleura. We examined the effect of height on pleural pressure in 15 anesthetized spontaneously breathing dogs. The vertical gradients in pleural pressure were 0.53, 0.42, 0.46, and 0.23 cmH2O/cm height for the head up, head-down, supine, and prone body positions, respectively. These vertical gradients were much less than the hydrostatic value (1 cmH2O/cm), indicating that the pleural liquid is not in hydrostatic equilibrium. In most body positions the magnitudes of pleural liquid pressure interpolated to midchest level were similar to the mean transpulmonary (surface) pressure determined postmortem. This suggests that pleural liquid pressure is closely related to the lung static recoil. PMID- 4030613 TI - Pleural space thickness in situ by light microscopy in five mammalian species. AB - The thickness of the pleural space was measured by a focusing method using a light microscope (X157, 2.5-micron depth of focus). In anesthetized animals, thin transparent parietal pleural windows were made by dissection of intercostal muscle. Multiple postmortem measurements were made of the combined thickness of the pleural space and the window by focusing in sequence on the lung surface and on 1- to 2-micron tantulum particles sprayed on the window. The window thickness was measured after creating a pneumothorax and retracting the lungs. In supine rabbits the pleural space measured at various heights on the costal surface was of uniform thickness (16 micron) except for a thicker region (62 micron) located within 3 mm of the most dependent part of the lung. The thicker region reverted to the uniform thickness after it was placed in a nondependent position by inverting the animal from the supine to prone position, indicating fluid drainage by gravity. In the prone position near midchest, pleural space thickness (t) averaged 6.9 micron in the mouse, 10.2 in the rat, 17.2 in the rabbit, 18.3 in the cat, and 23.6 in the dog. Animals of larger body mass (M, kg) had a wider pleural space: t = 13.1 X M0.20. There was no contact between the two pleurae, indicating that fluid lubrication facilitates sliding between the lung and chest wall. Based on the t vs. M relationship and estimates of the viscous flow of pleural liquid, pleural fluid exchange rate would be proportional to body mass and the work of sliding as a fraction of the work of breathing would be smaller in larger animals. PMID- 4030614 TI - Reflex compensation of voluntary inspiration when immersion changes diaphragm length. AB - When immersion alters inspiratory muscle operating lengths, spontaneously breathing humans maintain a constant tidal volume by reflex adjustment of inspiratory muscle activation (Reid et al. J. Appl. Physiol. 58: 1136-1142, 1985). We term this the operational length compensation reflex. The present experiment demonstrates that similar adjustments occur during voluntary respiratory maneuvers. Each of seven naive subjects sat in a tank with water at hip level. We trained them to reproduce an inspired volume (+/- 10%) at constant inspiratory duration. They received verbal feedback during training but not during the experiment. We measured surface electromyograms (EMGs) of diaphragm and intercostal muscles and tidal volume. After the subjects were trained, we made repeated measurements of 10 trained breaths with water at the hip and then again after raising water level to the xiphoid (which decreases lung volume and increases operating length of the diaphragm). In 30 of 42 trials there was a substantial fall in peak diaphragm EMG. In 10 trials this was sufficient to prevent any change in tidal volume. Inspiratory flow was more closely regulated than tidal volume. Subjects were not aware of making adjustments in drive. PMID- 4030616 TI - Photographic measurement of pleural surface motion during lung oscillation. AB - The regional pleural surface expansion of an excised dog lung was measured during high-frequency ventilation (HFV) using synchronized stroboscopic photography to stop lung motion at 20 evenly spaced intervals over a respiratory cycle during ventilation at 1 Hz with a volume of 100 ml, 15 Hz with 100 ml, or 30 Hz with 50 ml. The lungs were also photographed during quasi-static deflation. The pleural surface was marked with ink dots to form 84 approximately square figures. The side lengths and areas of each of the 84 "squares" were measured for each frame of each photo sequence. At 1 Hz and during the quasi-static deflation the lung ventilated nearly synchronously, although minor nonuniformities were noted on both small and large length scales. At 15 and 30 Hz, the lung expanded asynchronously and nonuniformly, with a 78% increase in surface expansion per 100 ml of tracheal tidal volume, as frequency was increased from 1 to 30 Hz. These nonuniformities in expansion suggest marked interregional airflow and elastic wave propagation in the parenchyma during HFV. PMID- 4030615 TI - Selenium deficiency potentiates paraquat-induced lipid peroxidation in isolated perfused rat lung. AB - Glutathione peroxidase (GSHPx), a seleno-enzyme, reduces lipid hydroperoxides while producing oxidized glutathione (GSSG), which can efflux from cells. To study the role of GSHPx in antioxidant defense, isolated lungs from selenium deficient rats were perfused for 2 h with or without 1 mM paraquat. Perfusate GSSG was measured as an index of GSHPx activity, and malondialdehyde (MDA) as an index of lipid peroxidation. Selenium deficiency decreased lung GSHPx activity 75 80%. During perfusion control lungs showed GSSG efflux of 8.5 +/- 4.5 nmol/h and with paraquat 49.1 +/- 12.1 nmol/h. Selenium-deficient lungs with or without paraquat showed GSSG efflux of 16.4 +/- 5.3 and 13.7 +/- 8.9 nmol/h, respectively. MDA efflux occurred only in paraquat-perfused selenium-deficient lungs (7.8 +/- 2.7 nmol/h). Lung homogenates from this group had lower GSH + GSSG than the other three groups. These results indicate an inverse correlation between GSSG efflux and MDA accumulation from paraquat-perfused lungs and suggest that increased turnover of the GSHPx reaction protects paraquat-perfused lungs from lipid peroxidation. PMID- 4030617 TI - Heat transfer pathways between fetal lamb and ewe. AB - Heat produced by the fetus exists to the mother by one of two principal routes: by fetal-maternal exchange in the placenta or through the fetal skin to the amniotic fluid and uterine wall. We measured heat conductances along each pathway to estimate the fraction of total heat exiting each route. Thermistors were placed in the fetal aorta, two different sites in the amniotic fluid, and in a maternal artery. Five days after surgery we injected a total of 280 ml of ice cold saline into the two separate amniotic fluid sites during a 45-s interval and measured the temperature response for the next hour. After one or two such injections the fetus was killed to cut off umbilical blood flow, and the experiment was repeated to measure the heat fluxes in the absence of placental heat exchange. Experimentally obtained temperature curves were compared with the predictions of a mathematical model. Heat conductances of the skin and uterine wall, as well as the fetal heat production, were estimated in the model using least-squares parameter optimization. In 10 fetal lambs, weighing 3.73 +/- 0.40 (SE) kg, total fetal heat production averaged 3.75 +/- 0.33 W X kg-1. The heat conductance of the uterine wall, 6.6 +/- 0.8 W X degrees C-1, was lower than that of the fetal skin, 10.2 +/- 1.0, and of the placenta, 25.7 +/- 2.9 W X degrees C 1, temperature gradient. We estimated that 84.5% of total fetal heat production exists by fetal-maternal exchange in the placenta with the remaining 15.5% exiting through the fetal skin. PMID- 4030618 TI - Interrupter technique for measurement of respiratory mechanics in anesthetized humans. AB - Flow (V), volume (V), and tracheal pressure (Ptr) were measured throughout a series of brief (100 ms) interruptions of expiratory V in six patients during anesthesia (halothane-N2O) and anesthesia-paralysis (succinylcholine). For the latter part of spontaneous expiration and throughout passive deflation during muscle paralysis, a plateau in postinterruption Ptr was observed, indicating respiratory muscle relaxation. Under these conditions, passive elastance of the total respiratory system (Ers) was determined as the plateau in postinterruption Ptr divided by the corresponding V. The pressure-flow relationship of the total system was determined by plotting the plateau in Ptr during interruption against the immediately preceding V. Ers averaged 23.5 +/- 1.9 (SD) cmH2O X l-1 during anesthesia and 25.5 +/- 5.4 cmH2O X l-1 during anesthesia-paralysis. Corresponding values of total respiratory system resistance were 2.0 +/- 0.8 and 1.9 +/- 0.6 cmH2O X l-1 X s, respectively. Respiratory mechanics determined during anesthesia paralysis using the single-breath method (W.A. Zin, L. D. Pengelly, and J. Milic-Emili, J. Appl. Physiol. 52: 1266-1271, 1982) were also similar. Early in spontaneous expiration, however, Ptr increased progressively during the period of interruption, reflecting the presence of gradually decreasing antagonistic (postinspiratory) pressure of the inspiratory muscles. In conclusion, the interrupter technique allows for simultaneous determination of the passive elastic as well as flow-resistive properties of the total respiratory system. The presence of a plateau in postinterruption Ptr may be employed as a useful and simple criterion to confirm the presence of respiratory muscle relaxation. PMID- 4030619 TI - Comparison of plethysmographic methods for obtaining thoracic gas volume in anesthetized dogs. AB - Thoracic gas volume (TGV) cannot be measured in the body plethysmograph by the standard spontaneous breathing technique (SB) when there is a significant respiratory center depression. In this case, either external compression of the chest wall (EC) or phrenic nerve stimulation (PhN) can be used to induce the pressure-volume changes necessary to calculate TGV. In the present study we compared TGV measured in eight pentobarbital-anesthetized dogs by SB, EC, PhN, and the standard He-dilution method. EC and simulated PhN were also used to measure the volume of a lung model, and EC was used to measure the volume of isolated lung lobes. A method for fast and accurate plethysmographic calibration is also described. In the intact dogs, SB, PhN, and He-dilution techniques gave similar results, but EC overestimated TGV. In the isolated lobes and lung model EC accurately measured volume. We speculate that EC induces substantial intersegmental and/or interlobal gas movement in intact lungs and that the pressure drop due to airway resistance causes proximal airway pressure to underestimate alveolar pressure changes, which induces overestimation in calculated TGV. We conclude that PhN is the method of choice to measure plethysmographic TGV when the respiratory center is depressed and that EC overestimates TGV in intact dogs. PMID- 4030620 TI - Small-animal traumatizer. AB - Clinical research, particularly among traumatized musculoskeletal patients, has been greatly inhibited by a lack of uniformity in the intensity of the injury. That is, few patients present identical injuries with respect to intensity and degree of soft tissue damage. Hence, researchers have gone to the experimental animal to achieve uniformity to the wound. Few studies, however, have reported effective methods of uniform traumatization. A small-animal traumatizer was developed at Brigham Young University that has proved reliable in producing a uniform contusion of 177 mm2 on the lateral thigh of the anesthetized experimental animal. If the investigator seeks an experimentally induced hematoma that approximates contusions seen clinically, one that is unvarying in every sample, something not available in traumatized patients, the small-animal traumatizer may be an important addition to your laboratory. PMID- 4030621 TI - Human smooth muscle cell cultures of the stomach. Morphologic and biochemical studies. AB - Smooth muscle cell cultures were prepared from stomach explants obtained surgically from 10 patients with duodenal ulcer. The cultured cells grew in either overlapping layers in "hills and valleys" or in parallel arrays. The ultrastructure studies showed plasmalemmal vesicles, bundles of myofilaments associated with dense bodies, and gap junctions. The synthesis of contractile proteins illustrated the preponderance of actin on myosin and tropomyosin. The synthesis of contractile proteins in stomach smooth muscle cell cultures is significantly higher than in skin fibroblast cultures, i.e. 20 X higher for myosin, 10 X higher for actin, and 30 X higher for tropomyosin. PMID- 4030622 TI - Sodium butyrate induced alterations in lysosomal enzyme activity. AB - Treatment of cultured HeLa cells with 5 mM sodium butyrate causes an inhibition of growth as well as extensive chemical and morphological differentiation. Lysosomal enzyme activity changes have been associated with both normal and neoplastic growth as well as many aspects of the neoplastic process. The comparative ultrastructural results show that the butyrate-treated cells have a more extensive internal membranous system than the untreated cells, whereas other organelles seem unaffected by the butyrate treatment. Methods for the histochemical localization of lysosomal acid phosphatase show a twofold increase in particulate reaction product in the butyrate-treated HeLa cells. Isolation of lysosomes followed by a comparative enzyme analysis shows a two to three fold increase in acid phosphatase activity per cell after 24 h of butyrate treatment, as well as three to four fold increase in beta-glucuronidase activity. These increases reverse within 24 h of removal of the butyrate from the culture medium. These results as interpreted suggest that butyrate treatment may be preventing sublethal autolysis by arresting the leakage of the lysosomal enzymes from the lysosome into the cytosol and thus allowing the cell to chemically and morphologically differentiate. PMID- 4030623 TI - Establishment of a continuous cell line from fibrotic schistosomal granulomas in mice livers. AB - A continuous murine cell line (GRX) was obtained from fibrotic granulomas induced in C3H/HeN mice liver by experimental infection with Schistosoma mansoni. This anchorage-dependent line produces composite connective tissue/extracellular matrix, displays morphological characteristics of myofibroblasts, and can, under appropriate conditions, accumulate fat droplets. GRX cells produce viral particles of retrovirus type. We consider GRX cell line to be representative of liver connective tissue cells, responsible for fibroplasia in liver fibrotic and granulomatous reactions. PMID- 4030625 TI - Isolation of tetraploid clones with high efficiency from diploid 3Y1 rat fibroblasts treated with sodium butyrate. AB - Sodium butyrate causes proliferation arrest with a G2 (4C) DNA content and induces formation of tetraploid cells upon removal of the inhibitor, in rat 3Y1 diploid fibroblasts. We isolated tetraploid clones from the butyrate-treated 3Y1 cells with high efficiency; among 21 clones randomly isolated, 5 were pure diploid, 7 were mainly tetraploid with a small contaminating diploid population, and 7 were pure tetraploid. Among the pure tetraploid clones, two showed doubled chromosome numbers with slightly broader distributions than that seen in parental 3Y1 cells. Butyrate further induced polyploid formation in the tetraploid cells thus produced, but octaploid cells that resulted could not be maintained for prolonged cultivation. We found no difference between the tetraploid and the (parental and parallel isolated) diploid clones in terms of colony-forming ability, proliferation rate, and sensitivity to density-dependent inhibition of proliferation. These results suggest that doubling of chromosome number by itself does not cause a change in proliferation property. The tetraploid clones had lower average saturation densities possibly due to enlargement of cell size represented by higher cellular protein content. PMID- 4030624 TI - Effects of retinoids on invasion of organ cultures of chick chorioallantoic membrane by adenovirus transformed cells. AB - Invasion of chick chorioallantoic membrane (CAM) organ cultures by rat 3Y1 cells transformed by the highly oncogenic human adenovirus type 12 (3Y1/12-10 cells) was inhibited by several retinoids tested. The anti-invasive activity of the retinoids was dependent on retinoid concentration and continuous (4 d) exposure of the CAM. The 50% retinoid dose (dose effective in achieving a response in half of the organ cultures) that inhibited invasion was 0.85 micrograms/ml of retinol palmitate, 0.39 micrograms/ml of retinoic acid, or 0.16 micrograms/ml of retinol acetate. This dose was of the same order of magnitude as that which induced CAM differentiation, and was three- to fourfold less than the dose that caused cytotoxic damage of CAM. In addition, the retinoids inhibited 3Y1/12-10 cell growth by approximately 40% at levels over 10-fold higher than those needed for anti-invasion activity. The findings suggest that the anti-invasive activity of retinoids was at least partly due to direct induction of cell differentiation of the CAM host tissue. PMID- 4030626 TI - 16,16-Dimethyl PGE2 and fatty acids protect hepatocytes against CCl4-induced damage. AB - 16,16-Dimethyl PGE2 (dmPGE2) has previously been shown to protect the in vivo rat liver against CCl4-induced damage. These studies were undertaken to determine if this protection could be demonstrated in vitro where factors of absorption, secretion, and blood flow are not present. Primary hepatocyte cultures were established by perfusing rat liver with collagenase. Hepatocytes were plated at a density of 2 X 10(4) cells/cm, allowed 90 min to attach, then stabilized in L15 medium for 18 h. Hepatocytes were then challenged with CCl4 with concomitant exposure to 10(-9) to 10(-5) M dmPGE2, stearic acid, oleic acid, or ethanol vehicle (0.00001 to 0.1%). After 1 h, challenge was aspirated and cells were stained with 0.04% trypan blue to determine viability. Hepatocytes in the vehicle groups took up more trypan when exposed to CCl4 than those treated with dmPGE2, stearic acid, or oleic acid at concentrations of 10(-9) to 10(-7) M. At 0.1% ethanol vehicle protected as well as all other treatments. Protection against CCl4 by dmPGE2, stearic, and oleic acids as well as high concentrations of ethanol may occur by altering the metabolism of CCl4. PMID- 4030627 TI - A rapid method for culturing guinea pig gastric mucous cell monolayers. AB - A method has been developed for growing confluent primary cultured monolayers of guinea pig gastric mucous cells suitable for in vitro electrophysiological, transport, and pharmacological studies. Isolated mucous cells were enriched on a one-step Percoll density gradient and plated on fibronectin-coated plastic dishes or in small cups with holes containing glutaraldehyde-fixed Vitrogen gels. These cups were designed to fit in Ussing chambers. Mucous cells attached, proliferated, and formed confluent monolayers in 3 d. The low cuboidal cells contained periodic acid Schiff-positive mucous granules that were negative by Bowie and indirect immunofluorescent staining for pepsinogen. Electron microscopy revealed polarized mucous cells with microvilli, mucous granules, microfilaments, small mitochondria, some vacuoles, and junctional complexes that excluded wheat germ agglutinin-peroxidase. No basal lamina was present. Monolayers could be maintained for over 2 wk but subcultures were not made. The cultures were virtually free of fibroblasts. Epithelial sheets produced by this simple and rapid method can be used for electrophysiological, ion transport, and pharmacological studies. PMID- 4030628 TI - The majority of independently transformed BHK cell clones share a single functional lesion which determines anchorage independence and influences tumorigenicity. AB - Expression of the anchorage-independent transformed phenotype in BHK 21/13 cells generally behaves as a recessive trait. When chemically induced and spontaneously arising transformants are fused to the nontransformed parent line, transformation is initially suppressed, reappearing after extended growth of the hybrids. In this paper, complementation for the expression of anchorage independence was sought among a large group of such transformants, all independently derived from BHK 21/13 cells. Tumorigenicity studies on selected hybrids and parental lines indicated that the in vitro trait of anchorage independence is an accurate indicator of in vivo neoplasia for these cells. Seventeen of the 18 clones tested did not complement one or more of three tester strains. This result indicates that anchorage independence arose in these clones as a result of lesions in the same genetic function and suggests that the final step in the progressive changes of carcinogenesis may frequently be restricted to lesions at a single locus. PMID- 4030629 TI - Liquid chromatographic determination of protein acid hydrolysate content in blended soy sauce. AB - Five methods were investigated for the determination of levulinic acid in soy sauce to determine the addition of protein hydrolysate, mainly acid hydrolysate of defatted soybeans. Best results were obtained by using liquid chromatography (LC) with 0.004 M HClO4 as the mobile phase and bromcresol purple as a post column reagent. An innovative LC method with 0.1% H3PO4 as eluant was developed for determination of levulinic acid at 280 nm in soy sauce. This was the most time-saving method. PMID- 4030630 TI - Gas chromatographic detection of D-(-)-2,3-butanediol and butyric acid produced by sporeformers in cream-style corn and canned beef noodle soup: collaborative study. AB - A gas chromatographic method that identifies sporeformers as the cause of spoilage in swollen cans of low-acid foods was collaboratively studied in 2 stages. Two organic compounds produced by sporeformers, D-(-)-2,3-butanediol and butyric acid, are measured in the upper phase after centrifugation of the liquid portion of the can contents. Each sample is assayed on 2 packed columns designed for the assay of aqueous solutions of volatile fatty acids, using flame ionization detectors. For study 1, 16 duplicate inoculated cans of cream-style corn and beef noodle soup were sent to 9 collaborators. For study 2, 7 collaborators received 11 duplicate inoculated cans of the 2 foods. Duplicate uninoculated cans of each food served as negative controls. The inocula were 6 sporeforming organisms (4 Clostridium and 2 gas-forming Bacillus species) and 2 nonsporeformers. After the deletion of marginal samples, the percentages of correctly identified sporeformers and nonsporeformers in beef noodle soup were 83 (110/132) and 90 (54/60), respectively; corresponding percentages for cream-style corn were 80 (98/123) and 100 (35/35). The method has been adopted official first action. PMID- 4030631 TI - Liquid chromatographic determination of tenuazonic acid and alternariol methyl ether in tomatoes and tomato products. AB - A liquid chromatographic (LC) method for determining tenuazonic acid (TA) and alternariol methyl ether (AME) in tomatoes and tomato products is described. The Alternaria metabolites are extracted from a water slurry of the sample with CHCl3, the mixture is centrifuged, and the extract is fractionated on a silica gel column. Reverse phase LC with an ultraviolet detector (for TA) and a fluorescence detector (for AME) connected in series is used for final separation and determination. The limit of determination for TA and AME is 25 and 3 ng/g, respectively, with average recoveries from catsup of 83 and 68%, respectively. The LC method also detects alternariol, but interfering peaks in some samples prevent accurate quantitation. Chemical ionization mass spectrometry (CIMS) is used to confirm TA. Samples (142) of tomatoes collected from commercial processing lines were analyzed; TA was found in 73 samples (0.4-70 micrograms/g). PMID- 4030632 TI - Thin layer chromatographic determination of sterigmatocystin in cheese. AB - A one-dimensional thin layer chromatographic method has been developed for determining sterigmatocystin in cheese. Cheese is extracted with acetonitrile-4% KCl (85 + 15). A simplified liquid-liquid partition cleanup is used, and the sample extract is passed through a cupric carbonate column for final purification. Sterigmatocystin is visualized by spraying the plate with aluminum chloride. The fluorescence of the spot is enhanced 10-fold by additional plate spraying with a silicone-ether mixture, enabling sterigmatocystin detection and quantitation at 2 and 5 micrograms/kg, respectively. Average recoveries were 88.3 and 86.4% at the 10 and 25 micrograms/kg levels, respectively. PMID- 4030633 TI - Assessment of extraction procedures in the analysis of naturally contaminated grain products for deoxynivalenol (vomitoxin). AB - A comparison of 2 extraction solvent systems (acetonitrile-water, 21 + 4 and methanol-water, 1 + 1) and 3 mixing apparatus (high-speed blender, wrist-action shaker, and mechanical stirrer) was carried out for different extraction time periods. Methods were evaluated using uncontaminated corn spiked with pure deoxynivalenol (DON), field-inoculated (Fusarium graminearum) corn, and uncontaminated and naturally infected wheat in swine diets. After sample extraction, aliquots were passed through alumina-charcoal cleanup columns, evaporated to dryness, dissolved in 8% aqueous methanol, and injected onto the liquid chromatograph. Results confirm published reports of recoveries from DON spiked samples; however, longer extraction times (less than or equal to 120 min) were required for naturally contaminated samples. Use of the high-speed blender resulted in faster extractions, but in our laboratory more samples could be more conveniently extracted simultaneously with the wrist-action shaker or mechanical stirrer. Less carryover (co-extraction) of interfering contaminants was observed when acetonitrile-water was used vs methanol-water. Results emphasize the importance of careful evaluation of extraction procedures with not only spiked samples but also naturally contaminated samples to establish extraction times required for maximum deoxynivalenol recoveries. PMID- 4030634 TI - Liquid chromatographic analysis of dehydroacetic acid and its application to wines. AB - A simple liquid chromatographic procedure is described for determination of the preservative dehydroacetic acid (DHA) in wine. No cleanup procedure is necessary; the sample is injected onto an NH2 column without further pretreatment. The mobile phase is a 9 + 1 mixture of acetonitrile-sodium acetate buffer adjusted to pH 4 with acetic acid. Total run time is less than 10 min. Dehydroacetic acid is determined by using the absorbance at 307 nm; the detection limit is estimated to be 0.2 ppm. The method may also be suitable for detecting DHA in a variety of foodstuffs in low concentrations. PMID- 4030635 TI - Liquid chromatographic determination of carbadox residues in animal feed. AB - A liquid chromatographic (LC) method for determining residues of carbadox in the 0.01-10 ppm range in swine feed is described. Carbadox is extracted from ground feed with 25% acidified methanol-CHCl3, removed from emulsion-forming coextractables via an alumina column, separated from highly colored pigments by acid-base liquid-liquid partitioning, and finally isolated from interferences on a second alumina column. Isocratic reverse phase LC at 305 nm is used for quantitation. The average overall recovery at the 0.1, 0.5, and 1.0 ppm spike levels was 83.0% with a standard deviation of 2.04% and a coefficient of variation of 2.46%. PMID- 4030636 TI - Liquid chromatographic determination of carbadox and desoxycarbadox in medicated feeds and in porcine gastrointestinal tract. AB - A liquid chromatographic method for the assay of carbadox and desoxycarbadox in medicated feeds and porcine stomach and intestinal contents is described. Samples were extracted with dimethylformamide-water and cleaned up on an alumina column. The eluate was chromatographed using either gradient elution for simultaneous assay of both compounds or isocratic elution for carbadox only. Detection of carbadox by its native fluorescence yielded a sensitive and specific assay without interferences by metabolites or matrix components. The optimal UV absorption of desoxycarbadox was at 280 nm. Mean recoveries of carbadox in spiked feed and stomach contents were 104 and 97%, respectively; mean recovery of desoxycarbadox in stomach contents was 106%. The day-to-day reproducibility for carbadox in different feed samples and stomach contents samples had a coefficient of variation of 6-13%. PMID- 4030637 TI - Liquid chromatographic monitoring of the depletion of carbadox and its metabolite desoxycarbadox in swine tissues. AB - A liquid chromatographic method was used to monitor a depletion study of carbadox (and its most important metabolite, desoxycarbadox) in young pigs fed carbadox treated rations for 1 week. Carbadox was found in blood (20 ppb), blood serum (26 ppb), and muscle tissue 24 h after withdrawal from treated ration; residues were reduced to a trace (less than 2 ppb) in 48 h, and eliminated by 72 h. Desoxycarbadox, although not detected in blood, was found in muscle (17 ppb) 24 h after withdrawal; it was reduced to 9 ppb at 48 h and to a trace by 72 h. Although no carbadox was detected in liver 24 h after withdrawal, appreciable desoxycarbadox (125 ppb) was found in liver 24 h after withdrawal; it was reduced to 17 ppb at 48 h and to a trace by 72 h. Whereas only a trace of carbadox was found in kidney 24 h after withdrawal, 186 ppb desoxycarbadox was found in kidney at 24 h, 34 ppb at 48 h, and a trace at 72 h. No metabolite of carbadox other than desoxycarbadox was found in extracts of swine tissues during this medicated feed trial, and no metabolite was found in blood extracts by using the established methodology. The effect of tissue storage (aging) at -20 degrees C on levels of the drug and its metabolite was a modest alteration of residue levels. The inadvertent use of feed adulterated with furazolidone and initially medicated with chlortetracycline, sulfamethazine, and penicillin G, did not affect the uptake of carbadox in this depletion study or interfere with the analytical methodology. PMID- 4030639 TI - Liquid chromatographic determination of vitamin K1 trans- and cis-isomers in infant formula. AB - The normal phase liquid chromatographic (LC) method for determination of trans- and cis-isomers of vitamin K1 (phylloquinone) in infant formula described here uses an Apex silica column, isocratic elution, and UV absorption detection at 254 nm. Vitamin K1 is extracted quantitatively from the product matrix by pretreating the as-fed liquid with concentrated ammonium hydroxide and methanol, and then extracting it with a 2:1 mixture of dichloromethane and isooctane. The extract is cleaned up by silica open-column chromatography and concentrated for LC analysis. For trans-vitamin K1, the method precision is less than or equal to 3.3% RSD (relative standard deviation), and the spike recovery is 98 +/- 4%. For cis vitamin K1, the precision is less than or equal to 12% RSD, determined at levels near the detection limit, and the spike recovery is 95 +/- 9%. The detection limit is 0.3 ng for both isomers at signal/noise = 3. PMID- 4030638 TI - Assessment of protein quality methodology for infant formulas. AB - Rat bioassay was used to assess the protein quality of powdered infant formulas and to evaluate the feasibility of using modified casein diets (containing the same source and level of fat and carbohydrate contributed by the infant formulas) as reference standards. Modification of the casein diet to match the milk-based formulas caused a significant reduction in weekly protein efficiency ratios (PER) and net protein ratios (NPR) at the third and fourth weeks. Modification of the casein diet to stimulate the soy-based formulas had no significant effect on NPR values; PER values were more varied. When PER and NPR values of the powdered milk based formulas were expressed relative to the unmodified reference standard, the relative values were lower than when each matched reference was used. With few exceptions, the relative weekly PER values of the soy-based formulas were similar regardless of the standard used. The relative NPR values of the formulas had a pattern similar to the relative PER values. The data indicate that protein quality evaluation of infant formulas using rat bioassay warrants the use of matched casein reference diets for each type of formula. PMID- 4030640 TI - Improved liquid chromatographic determination of riboflavin in milk and dairy products. AB - Reported here is a simple liquid chromatographic (LC) method for the determination of riboflavin in milk (liquid, evaporated, and dry), yogurt, and cheese. The method involves passing liquid samples or filtrates of semisolid and solid samples through a C18 cartridge. Retained riboflavin is then eluted with an aliquot of 50% methanol in 0.02M acetate buffer of pH 4. A volume of the eluate is injected into the LC system consisting of a C18 column, a solvent of water methanol-acetic acid (65 + 35 + 0.1, v/v) with a flow rate of 1 mL/min, and a UV detector set at 270 nm. The method is precise and accurate and compares favorably with the present AOAC method. Moreover, it involves fewer sample preparation steps and has a total analysis time of less than 1 h. PMID- 4030641 TI - Extraction of light filth from whole peppermint leaves: collaborative study. AB - Results are reported for a collaborative study of a method for the extraction of light filth from whole peppermint leaves. A 5 g sample is defatted with isopropanol in a simple reflux appartus. Rat hairs, insect fragments, and whole insects are isolated by wet sieving on a No. 230 sieve, a deaerating boil in 40% isopropanol solution, flotation with Tween 80-Na4EDTA (1 + 1) and mineral oil heptane (85 + 15), and trappings in a Wildman trap flask. Average recoveries obtained by 6 collaborators for 3 spike levels of rat hairs (5, 10, 15) were 83.3, 87.5, and 82.2%, respectively. For whole insects (5, 10, 15) recoveries averaged 85.0, 80.0 and 77.2% respectively; for insect fragments (20, 30, 50) recoveries averaged 79.6, 88.3, and 84.8%, respectively. The average recoveries for the 3 levels of each analyte were not significantly different. The method has been adopted official first action. PMID- 4030642 TI - Determination of internal insect infestation of oats: collaborative study. AB - An improved method has been developed for determining internal insect infestation of oat kennels. The method involves alcohol defatting and acid hydrolysis of the cracked oats, wet sieving to remove the acid, transfer to a 2 L Wildman trap flask, deaeration by boiling, and treatment with Tween 80-Na4EDTA. Insects are extracted with light mineral oil. Reports from 6 collaborators showed that recoveries averaged 88.98% for adult insect heads and 97.22% for larvae. The method has been adopted official first action. PMID- 4030643 TI - Mass spectrometry and identification of sterols in vegetable oils as butyryl esters and relative quantitation by gas chromatography with flame ionization detection. AB - Electron ionization mass spectrometry (MS) of sterol butyrates is described. Fragmentation of common sterol butyrates is related to structure and is discussed in relation to the fragmentation of free sterols and of commonly used sterol derivatives. Derivatized samples of vegetable oils are introduced using a 10 m capillary gas chromatographic (GC) column for complete separation of the sterol butyrates. Quantitation of sterol butyrates in vegetable oils by packed column GC/flame ionization detection is based on percent relative area of peaks identified by MS. Results of analyses of sunflower, castor, rapeseed, and virgin olive oils, and other oils are presented. These techniques have been applied to the rapid screening of marketed olive oils for possible adulteration. PMID- 4030644 TI - Capillary gas chromatographic-mass spectrometric determination of fluoroacetate residues in animal tissues. AB - A method for the quantitative determination of fluoroacetate (FAC) residues in animal tissues is described. The procedure involves tungstic acid extraction, partitioning into ethyl acetate, evaporation of ethyl acetate, derivatization with pentafluorobenzyl bromide (PFB), and analysis of the resulting derivative (PFB-FAC) by capillary gas chromatography-mass spectrometry (CGC-MS) with specific ion monitoring (SIM). The tungstic acid system extracted 96.8 +/- 4.2% of the endogenous 14C-1080 residues in rat tissues. Recovery of FAC during the extraction, purification, and derivatization procedures is established by use of a 14C-FAC spike. 1,2-Dibromobenzene is used as an internal standard for the CGC MS analysis. PFB-FAC is identified on the basis of comparative retention times and the relative intensities of m/z 257.9 and 181.0. PFB-FAC is quantitated by comparing the response at m/z 257.9 to a PFB-FAC standard curve. Routine sensitivity of the method allows determination of 10 ppb fluoroacetate in tissue. PMID- 4030645 TI - Liquid chromatographic determination of N-methylcarbamate insecticides and metabolites in crops. I. Collaborative study. AB - A liquid chromatographic (LC) multiresidue method for determining residues of N methylcarbamate insecticides in crops was collaboratively studied in 6 laboratories. Methanol and a mechanical ultrasonic homogenizer are used to extract the carbamates. Water-soluble plant coextractives and nonpolar plant lipid materials are removed from the carbamate residues by liquid-liquid partitioning. Additional crop coextractives (e.g., carotenes, chlorophylls) are removed with a Nuchar SN-silanized Celite column. The carbamate residues are then separated on a reverse phase LC column, using an acetonitrile-water gradient mobile phase. Eluted residues are detected by an in-line post-column fluorometric detection technique. Seven carbamates and 2 carbamate metabolites were included in the collaborative study. Each collaborator determined all the carbamates at 2 levels (approximately 0.05 ppm and United States tolerance) in blind duplicate samples of grapes and potatoes. Fortified and control samples were analyzed. Repeatability coefficients of variation for all the carbamates on the 2 crops averaged 4.7% and ranged from 2.4 to 7.1%. Reproducibility coefficients of variation for all the carbamates on the 2 crops averaged 8.7% and ranged from 5.3 to 12.4%. Accuracy, measured by comparison with fortification values, averaged 95% and ranged from 79 to 103%. The estimated limit of quantitation is 0.01 ppm. The method has been adopted official first action. PMID- 4030646 TI - Liquid chromatographic determination of N-methylcarbamate insecticides and metabolites in crops. II. Analytical characteristics and residue findings. AB - Four laboratories obtained 177 carbamate recovery values using a liquid chromatographic method. The average recovery of 11 carbamates (aldicarb, aldicarb sulfone, bufencarb, carbaryl, carbofuran, 3-hydroxy carbofuran, 3-keto carbofuran, methiocarb, methiocarb sulfoxide, methomyl, and oxamyl) from 14 crops was 99% with a coefficient of variation of 8% (0.03-1.8 ppm fortification levels). No statistical difference in recovery was found between oxime and phenyl carbamates, or between parent and metabolite carbamates. Average recovery of aldicarb sulfoxide was 59% due to loss in the liquid-liquid partitioning because of the polarity of this compound. A fifth laboratory contributed 34 carbamate recoveries (average 99%) on table-ready food products for 4 carbamates. Bendiocarb, dioxacarb, isoprocarb, and propoxur are also quantitatively recovered through the method. Previously reported carbamate and noncarbamate recovery data are also discussed. In the Food and Drug Administration's (FDA) analysis of 319 samples (mainly crops), 86 (27%) were found to contain residues of carbamate insecticides and/or toxic carbamate metabolites. Carbaryl and methomyl were the most common carbamate residues found on the food products excluding the aldicarb sulfone and sulfoxide residues found on potatoes. In one FDA Total Diet Program "market basket", 11 of 69 table-ready food commodities contained from 0.005 to 0.094 ppm carbamate residues. Carbaryl was the most prevalent residue. Several laboratories reported adverse effects on the determinative system when inadequately purified reagents were used. PMID- 4030647 TI - Determination of ethylenethiourea in grapes and wine. AB - Residues of ethylenethiourea (ETU) in grapes and wine were determined by capillary gas chromatography and paper chromatography, without a cleanup step, and after derivatization to S-benzyl-ETU. The detection limit was 0.0002 mg/kg for flame ionization detection, 0.008 mg/kg for paper chromatography with photodensitometric evaluation of the detected spot. Results were compared with a generally used GC method specifying electron capture detection of trifluoroacetylated S-benzyl-ETU. The recoveries of ETU in grapes and wine at different concentration levels were determined. ETU residues were determined in treated grapes but no residues were detected in wine. PMID- 4030648 TI - Gas chromatographic determination of CCRL583 perfluorinated alcohol fumigant residues. AB - A gas chromatographic method is described for the determination of CCRL583 (1,1,1,3,3,4,4,4-octafluoro-2-(trifluoromethyl)-2-butanol). The sample is extracted with acetonitrile and cleaned up by liquid-liquid extraction, first with a basic aqueous solution and finally with an acid aqueous solution. The final organic layer is injected into a gas chromatograph equipped with a column packed with terephthalic acid-terminated Carbowax 20M. Recovery of CCRL583 from fortified wheat and peanuts was 91-108%. PMID- 4030649 TI - Capillary gas chromatographic determination of prometryn and its degradation products in parsley. AB - Residue analysis of the herbicide prometryn (2,4-bis(isopropylamino)-6-methylthio 1,3,5-triazine) is widely known, but an analytical method for determining its metabolities or degradation products in addition to the parent chemical has not yet been reported in the literature. The procedure reported here is for the extraction and determination of prometryn and 2 metabolites, 2-amino-4 isopropylamino-6-methyl-thio-1,3,5-triazine and 2,4-diamino-6-methylthio-1,3,5 triazine, in parsley. Crops were extracted with 2-propanol followed by concentration of the extract and partitioning with a minimum amount of hexane in the presence of a large excess of water to remove most of the green pigment. The aqueous phase was divided into 2 equal halves: (A) One-half portion was partitioned with dichloromethane in the presence of saturated sodium chloride solution, the dichloromethane phase was separated, and the aqueous phase was discarded. The organic solvent was evaporated, and the contents were reconstituted in petroleum ether before prometryn analysis. (B) The other half was made slightly alkaline with ammonium hydroxide solution and was partitioned with ethyl acetate in the presence of saturated sodium chloride solution. The ethyl acetate phase was concentrated, centrifuged to remove any turbidity, and analyzed for the 2 metabolities above. Fused silica capillary gas chromatography (GC) with nitrogen-phosphorus (N-P) detection was used for quantitation. The limit of detection was 0.05 mg/kg for all the compounds examined. Recoveries from fortified parsley samples ranged from 59 to 73% at fortification levels of 0.05 to 1.0 mg/kg. PMID- 4030650 TI - Simplified cleanup and liquid chromatographic determination of oxamyl residues in potato tubers. AB - A simple and efficient method is presented for the extraction, cleanup, and liquid chromatographic (LC) determination of oxamyl residues in potato tubers. Samples are extracted with methanol, partitioned into dichloromethane, and cleaned up using Sep-Pak Florisil cartridges. LC determination is performed using a Zorbax PSM 60 size exclusion column with an acetonitrile-water (1 + 9) mobile phase and UV detection at 254 nm. Recovery of oxamyl from spiked control tubers averaged 94.1 and 85.9% at fortification levels of 0.4 and 0.08 micrograms oxamyl/g tuber, respectively. The minimum detectable concentration of oxamyl by this method is 0.01 micrograms/g. PMID- 4030651 TI - Statistical examination of AOAC use-dilution method for testing disinfectant efficacy. AB - The AOAC use-dilution method is examined from a statistical viewpoint by using the fundamental concept of operating characteristic curves to focus attention on the inadequately defined aspects of the acceptance/rejection criteria used for disinfectant registration and enforcement purposes. PMID- 4030652 TI - New FDA migration cell used to study migration of styrene from polystyrene into various solvents. AB - A new cell was evaluated for studying the migration of components of plastic food packaging materials into various food simulating solvents. Data obtained using this cell to study the migration of styrene from polystyrene at 40 and 70 degrees C are presented. Food simulating solvents tested were: water; 3% acetic acid; 8, 20, 50, and 100% ethanol; corn oil; HB-307; heptane; hexadecane; and decanol. An iterative Basic computer program is described that fits the migration vs time data obtained to mathematical models, based on Ficks' law, yielding migrant/polymer diffusion coefficients (Dp). Dp values determined for styrene migration from polystyrene at 40 and 70 degrees C were 3 X 10(-13) and 4 X 10( 12) sq. cm/s, respectively. PMID- 4030653 TI - Determination of acrylonitrile in foods by headspace-gas chromatography with nitrogen-sensitive detection: collaborative study. AB - A headspace-gas chromatographic procedure, with nitrogen-phosphorous (N-P) specific detection for the determination of acrylonitrile (AN) in cold pack cheese, peanut butter, honey butter, and margarine, was collaboratively studied. Seven laboratories analyzed 7 samples of each food for AN at levels ranging from 5 to 60 ppb. For cold pack cheese, mean recoveries for AN added at about 5, 15, and 50 ppb were 65.9, 92.4, and 96.6%, respectively; for peanut butter, mean recoveries for AN added at about 10, 30, and 60 ppb were 59.6, 61.7, and 66.5%, respectively; for honey butter, mean recoveries for AN added at 5, 15, and 50 ppb were 88.6, 96.4, and 94.6%, respectively; and for margarine, mean recoveries for AN added at 5, 15, and 50 ppb were 130.6, 91.9, and 88.7%, respectively. The overall coefficients of variation for cold pack cheese, peanut butter, honey butter, and margarine spiked at the above levels were 67.7, 22.0, and 38.5%; 71.8, 23.8, and 23.8%; 45.3, 30.4, and 13.0%; and 79.7, 38.9, and 16.2%, respectively. PMID- 4030655 TI - Using the professional or in-house model in a medical setting. PMID- 4030656 TI - Processing Technical Pan. PMID- 4030654 TI - Liquid chromatographic determination of quinine, hydroquinine, saccharin, and sodium benzoate in quinine beverages. AB - A liquid chromatographic (LC) method is described for the determination of quinine, hydroquinine, sodium saccharin, and sodium benzoate in soft drinks. The method involves simple sample preparation, direct injection onto an octadecylsilane column, and elution with a methanol-acetonitrile-water-acetic acid (20 + 10 + 70 + 1) mobile phase. Eluted constituents are measured spectrophotometrically at 254 nm. The relationship between peak height and concentration was linear between 20 and 120 micrograms/mL for quinine. A relative standard deviation of 0.82% was obtained for commercial samples spiked with quinine, and the average recovery was 100.3%. The proposed procedure is accurate and rapid and can also detect hydroquinine (a natural contaminant of quinine), sodium saccharin, and sodium benzoate. Linear responses ranged from 0.45 to 20 micrograms/mL for hydroquinine, from 54.8 to 219 micrograms/mL for sodium saccharin, and from 10.1 to 145.1 micrograms/mL for sodium benzoate. The reproducibility of the LC method was evaluated with standard solutions of hydroquinine, sodium saccharin, and sodium benzoate, which produced relative standard deviations of 0.42, 0.46, and 1.13%, respectively. The average recoveries for sodium saccharin and sodium benzoate from spiked samples were 99.4 and 100.2%, respectively. PMID- 4030657 TI - Photography and patient's rights. PMID- 4030658 TI - Photography of microradiography. PMID- 4030659 TI - Copying CT scans with a reasonably priced video printer. PMID- 4030660 TI - Cell counts in cerebral cortex of an autistic patient. AB - Numbers of neurons and glia were counted in the cerebral cortex of one well documented case of autism and two age- and sex-matched controls. Areas in which cell counts were made were primary auditory cortex, Broca's speech area, and auditory association cortex. No consistent differences in cell density were found between the brains of the autistic patient and the control patients. PMID- 4030661 TI - Deprivation of early sensorimotor experience and cognition in the severely involved cerebral-palsied child. AB - Severely quadraplegic cerebral-palsied children suffer profound deprivation of early sensorimotor experiences considered by Piagetian theory as critical to the development of cognitive structures. In the present study, 34 children quadraplegic from birth, ranging in age from 9 months to 12 years, were tested for level of object permanence which, according to Piaget, signals the emergence of mental representation. Sixteen demonstrated high levels of object permanence. Severity of physical handicap accounted for less than 15% of the variation in scores. With severity held constant, mental age explained 25% of the variance. These results indicate that early cognitive milestones can be achieved by children severely physically handicapped since birth and that general intellectual level may be more important than severity of the motor handicap in determining such achievement. PMID- 4030662 TI - Effect of using an auditory trainer on the attentional, language, and social behaviors of autistic children. AB - Two groups of seven autistic children wore an auditory trainer for an average of 24 minutes per day over two 5-week periods interspersed with 5-week control periods in a time series design. Videotapes were coded for three attentional states (normal, withdrawn, attacking), for verbalization and signing, and for appropriate and acceptable behaviors. Results demonstrated a decrease in time spent withdrawn and increases in signing and in school-appropriate behavior. Results are interpreted as congruent with Katz's theory of reduced attention due to deficits in auditory conductance. PMID- 4030663 TI - Parental ratings of treatments of self-injurious behavior. AB - This study examined (a) how parents of autistic children, parents of other handicapped children, and parents of nonhandicapped children rate, as a whole, acceptability of time-out, differential reinforcement, overcorrection, and shock as treatments for self-injurious behavior, and (b) whether these parents show differences, as groups, in ratings of these treatments. On the Treatment Evaluation Inventory, all groups consistently rated differential reinforcement, time-out, and overcorrection as acceptable and shock as unacceptable. Differential reinforcement was consistently rated as the most acceptable, but the groups differed in ratings of acceptability of other treatments. On the Semantic Differential, ratings of differential reinforcement, overcorrection, and time-out did not differ. However, shock was consistently rated as the most potent and active of treatments as well as the most unacceptable. The implications of these findings for treatment of autistic and other handicapped children are discussed. PMID- 4030664 TI - Familial heterogeneity in infantile autism. AB - The incidence of autism and cognitive disability was assessed in the biological siblings of 29 autistic probands subdivided on the basis of IQ. A significant clustering of autism and nonspecific intellectual retardation was found in the siblings of severely retarded autistic probands which was not present in the siblings of our higher-functioning autistic sample. These findings suggest that there may be etiological differences in autism, depending on the degree of associated mental retardation. PMID- 4030665 TI - Handedness and cognitive functions in pervasive developmental disorders. AB - This paper is concerned with what abnormal handedness in Pervasive Developmental Disorders (PDD) reveals about the presence, lateralization, and severity of cerebral dysfunction in this population. From previous work, it was predicted that left-handedness would be elevated in the sample and that mixed-handedness subjects should be more impaired than those with established hand dominance. A battery of cognitive and motor tests were administered to a group of PDD children with autistic symptoms, and performance was compared for the left-handed, right handed, and mixed-preference children. It was found that left-handers tended to do better than right-handers on all cognitive measures, while the mixed preference children tended to be the lowest on all cognitive measures. No differences were found on motor measures. An extension of the Satz (1972) model, assuming early brain damage, was developed to explain the superiority of the left handed children; an alternative explanation assuming anomalous lateralization patterns in the natural left-handers was also suggested. PMID- 4030667 TI - Brief report: implication of EEG diagnoses in the subclassification of infantile autism. PMID- 4030666 TI - Brief report: screening children with autism for fragile-X syndrome and phenylketonuria. PMID- 4030669 TI - Short course tuberculous chemotherapy. PMID- 4030668 TI - A case of autism and mosaic of trisomy 8. PMID- 4030670 TI - Cell mediated immunity in leprosy with neurological complications. PMID- 4030671 TI - Evaluation of creatine phosphokinase in cases of cerebrovascular accidents. PMID- 4030672 TI - A comprehensive study of autonomic nervous system dysfunctions in diabetes mellitus. PMID- 4030673 TI - Oral oxyfedrine on left ventricular performance in patients of ischaemic heart disease. PMID- 4030674 TI - A study of serum glycoproteins in diabetes mellitus. PMID- 4030675 TI - Thyroid function in non insulin dependent diabetes mellitus. PMID- 4030676 TI - 'Top of the basilar' syndrome. PMID- 4030677 TI - Serum immunoglobulins in malaria. A preliminary report. PMID- 4030679 TI - Advances in the treatment of cysticercosis: praziquantel. PMID- 4030680 TI - Bronchoalveolar lavage. PMID- 4030678 TI - Short course intermittent chemotherapy in pulmonary tuberculosis. PMID- 4030681 TI - Viral hepatitis. PMID- 4030682 TI - Needle biopsy of the lung with Menghini needle. PMID- 4030683 TI - Evidence of glycosylation of platelet proteins in diabetics. PMID- 4030684 TI - Transient brain stem dysfunction manifesting as locked-in syndrome secondary to alcoholism. PMID- 4030685 TI - Rhino orbital mucormycosis treated with amphotericin B with successful outcome. PMID- 4030686 TI - Nail patella syndrome. PMID- 4030687 TI - Primary intraventricular haemorrhage. PMID- 4030688 TI - Copper sulphate poisoning, hemolysis and methaemoglobinemia. PMID- 4030689 TI - Genetic structure of populations of Legionella pneumophila. AB - The genetic structure of populations of Legionella pneumophila was defined by an analysis of electrophoretically demonstrable allelic variation at structural genes encoding 22 enzymes in 292 isolates from clinical and environmental sources. Nineteen of the loci were polymorphic, and 62 distinctive electrophoretic types (ETs), representing multilocus genotypes, were identified. Principal coordinates and clustering analyses demonstrated that isolates received as L. pneumophila were a heterogeneous array of genotypes that included two previously undescribed species. For 50 ETs of L. pneumophila (strict sense), mean genetic diversity per locus was 0.312, and diversity was equivalent in ETs represented by isolates recovered from clinical sources and those collected from environmental sources. Cluster analysis revealed four major groups or lineages of ETs in L. pneumophila. Genetic diversity among ETs of the same serotype was, on average, 93% of that in the total sample of ETs. Isolates marked by particular patterns of reactivity to a panel of nine monoclonal antibodies were also genetically heterogeneous, mean diversity within patterns being about 75% of the total. Both Pontiac fever and the pneumonic form of legionellosis may be caused by isolates of the same ET. The genetic structure of L. pneumophila is clonal, and many clones apparently are worldwide in distribution. The fact that L. pneumophila is only 60% as variable as Escherichia coli raises the possibility that isolates recovered from clinical cases and man-made environments are a restricted subset of all clones in the species as a whole. PMID- 4030690 TI - Waveform analysis and structure of flagella and basal complexes from Bdellovibrio bacteriovorus 109J. AB - The structure of sheathed flagella from Bdellovibrio bacteriovorus was investigated. The first three periods of these flagella were characterized by progressively smaller wavelengths and amplitudes in periods more distal to the cell. The damped appearance was due to a single nonrandom transition between two helical structures within each filament. The intersection of the two helices, one of which was a threefold-reduced miniature of the other, occurred at a fixed distance along the filament and resulted in a shift in the flagellar axis. Flagella increased in length as the cells aged and assumed a constant miniature waveform at their distal ends. The core filament was the principal determinant of flagellar morphology. It was composed of 28,000- and 29,500-dalton polypeptides. The 28,000-dalton subunits were located in the cell-proximal segment of the filament, and the 29,500-dalton subunits were located in the more distal region. The heteromorphous appearance of bdellovibrio flagella arose from the sequential assembly of these subunits. The basal complex associated with core filaments was examined because of its potential involvement in sheath formation. Bdellovibrio basal organelles were generally similar to those of other gram-negative species, but appeared to lack a disk analogous to the outer membrane-associated L ring which is a normal component of gram-negative basal complexes. PMID- 4030691 TI - Isolation and composition of sheathed flagella from Bdellovibrio bacteriovorus 109J. AB - A procedure was developed for the purification of sheathed flagella from Bdellovibrio bacteriovorus 109J. Preparations of isolated flagella appeared as filaments 28 nm in diameter, did not vary in sheath content by more than 10% from the mean, and contained 50% protein, 38% phospholipid, and 12% lipopolysaccharide (LPS) by weight. The sheath was readily solubilized by Triton X-100, whether or not EDTA was present, and contained all of the LPS and phospholipid and 30 to 40% of the protein of the intact flagella; sedimentable core filament polypeptides accounted for the remainder. Flagellar LPS was significantly enriched in nonadecenoic acid (19:1) and depleted in beta-hydroxymyristic acid relative to outer membrane LPS from intraperiplasmically grown bdellovibrios. These observations suggest that the sheath is a stable domain distinct from the bulk of the outer membrane. The sheath also contained substantially more phospholipid (57%) and less protein (26%) of a more heterogeneous composition than that of previously described outer membranes. This unusual balance of constituents was predicted to result in a fluid membrane compatible with a model for the generation of motility by rotation of the core filament within a highly flexible sheath. PMID- 4030693 TI - Effect of changes in the osmolarity of the growth medium on Vibrio cholerae cells. AB - The rate and extent of lysis of Vibrio cholerae cells under nongrowing conditions were dependent on the osmolarity of the growth medium. Gross alterations in cellular morphology were observed when V. cholerae cells were grown in media of high and low osmolarity. The rate of lysis of V. cholerae cells under nongrowing conditions increased after treatment with chloramphenicol. Chloramphenicol treated V. cholerae 569B cells showed formation of sphaeroplast-like bodies in medium of high osmolarity, but not in low osmolarity. Changes in the osmolarity of the growth medium also regulated the expression of the outer membrane proteins. This regulation was abolished if V. cholerae cells were grown in Pi depleted medium. Analysis of the lytic behavior and composition of outer membrane proteins of an osmotically fragile mutant strain revealed a similar dependence on the osmolarity of the growth medium. PMID- 4030692 TI - Uptake of intact nucleoside monophosphates by Bdellovibrio bacteriovorus 109J. AB - The degraded nucleic acids and ribosomes of its prey cell provide Bdellovibrio bacteriovorus 109J with a source of ribonucleoside monophosphates and deoxyribonucleoside monophosphates for biosynthesis and respiration. We demonstrate that bdellovibrios, in contrast to almost all other bacteria, take up these nucleoside monophosphates into the cell in an intact, phosphorylated form. In this way they are able to assimilate more effectively the cellular contents of their prey. Studies with UMP and dTMP demonstrate that they are transported and accumulated against a concentration gradient, achieving internal levels at least 10 times the external levels. Treatment of the bdellovibrios with azide or carbonyl cyanide m-chlorophenylhydrazone eliminates their ability to either transport or maintain accumulated UMP and suggests the presence of a freely reversible exchange mechanism. There are at least two separate classes of transport systems for nucleoside monophosphates, each exhibiting partial specificity for either ribonucleoside monophosphates or deoxyribonucleoside monophosphates. Kinetic analyses of UMP transport in different developmental stages of strain 109J indicate that each stage expresses a single, saturable uptake system with a distinct apparent substrate affinity constant (Kt) of 104 microM in attack phase cells and 35 microM in prematurely released growth phase filaments. The capacity for transport of UMP by the growth phase filaments was 2.4 times that of the attack phase cells. These data, in addition to the apparent lack of environmental control of UMP transport capacity in attack phase cells, suggest that there are two transport systems for UMP in bdellovibrios and that the high-affinity, high-capacity growth phase system is developmentally regulated. PMID- 4030694 TI - Cell volume regulation in Mycoplasma gallisepticum. AB - Mycoplasma gallisepticum cells incubated in 250 mM NaCl solutions in the absence of glucose showed a progressive fall in intracellular ATP concentration over a period of 2 to 3 h. When the ATP level fell below 40 microM the cell began to swell and become progressively permeable to [14C]inulin and leak intracellular protein and nucleotides. The addition of nondiffusable substances such as MgSO4 or disaccharides prevented swelling, suggesting that NaCl (and water) entry was due to Gibbs-Donnan forces. The addition of glucose after the initiation of cell swelling increased intracellular ATP, induced cell shrinkage, and prevented the release of intracellular components. The ATPase inhibitor dicyclohexylcarbodiimide, which collapsed the chemical and electrical components of the proton motive force, caused rapid cell swelling in the presence of glucose (and high intracellular ATP levels). Extracellular impermeable solutes such as MgSO4 and disaccharides prevented swelling of dicyclohexylcarbodiimide-treated cells incubated in NaCl. It was postulated that Na+ that diffused into the cell was extruded by an electrogenic Na+-H+ exchange (antiport) energized by the proton motive force established by the dicyclohexylcarbodiimide-sensitive H+ ATPase. PMID- 4030695 TI - Sodium and proton transport in Mycoplasma gallisepticum. AB - When washed cells of Mycoplasma gallisepticum were incubated at 37 degrees C in 250 mM 22NaCl, the intracellular Na+ increased, and the K+ decreased. The addition of glucose to these Na+-loaded cells caused Na+ efflux and K+ uptake (both ions moving against concentration gradients). This effect of glucose was blocked by the ATPase inhibitor dicyclohexylcarbodiimide, which prevents the generation of a proton motive force in these cells. In additional experiments, Na+ extrusion was studied by diluting the 22Na+-loaded cells into Na+-free media and following the loss of 22Na+ from the cells. Glucose stimulated 22Na+ extrusion in such cells by a dicyclohexylcarbodiimide-sensitive mechanism. Proton movement was studied by measuring the pH gradient across the cell membrane with the 9-aminoacridine fluorescence technique. Glucose addition to cells preincubated with cations other than Na+ resulted in cell alkalinization (which was prevented by dicyclohexylcarbodiimide). This observation is consistent with the operation of a proton-extruding ATPase. When glucose was added to Na+-loaded cells and diluted into Na+-free media, intracellular acidification was observed, followed several minutes later by a dicyclohexylcarbodiimide-sensitive alkalinization process. The initial acidification was probably due to the operation of an Na+-H+ antiport, since Na+ exit was occurring simultaneously with H+ entry. When Na+-loaded cells were diluted into Na+-containing media, the subsequent addition of glucose resulted in a weak acidification, presumably due to H+ entry in exchange for Na+ (driven by the ATPase) plus a continuous passive influx of Na+. All of the data presented are consistent with the combined operation of an ATP-driven proton pump and an Na+ -H+ exchange reaction. PMID- 4030696 TI - Thermoanaerobacter ethanolicus in a comparison of the growth efficiencies of thermophilic and mesophilic anaerobes. AB - Maintenance coefficients and theoretical maximum growth yields, with respect to both substrate and ATP, were estimated for Thermoanaerobacter ethanolicus growing in a glucose-limited, continuous culture. A comparison of these values with those for other bacteria showed that, contrary to predictions by others, anaerobic thermophiles had neither low observed growth yields nor high maintenance energy coefficients. PMID- 4030697 TI - Role of protein subunits in Proteus rettgeri penicillin G acylase. AB - Penicillin G acylase from Proteus rettgeri is an 80,000- to 90,000-dalton enzyme composed of two nonidentical subunits. Both subunits were required for enzymatic activity. The 65,000-dalton beta subunit contained a phenylmethylsulfonyl fluoride-sensitive residue required for enzymatic activity, and the 24,500-dalton alpha subunit contained the domain that imparts specificity for the penicillin side chain. PMID- 4030698 TI - Sucrose uptake is driven by the Na+ electrochemical potential in the marine bacterium Vibrio alginolyticus. AB - Na+ was found to be essential for the accumulation of sucrose by Vibrio alginolyticus. Sucrose uptake was completely inhibited by the addition of proton conductor at neutral pH, but not at alkaline pH, where the primary electrogenic Na+ pump generates the Na+ electrochemical gradient. We therefore conclude that sucrose transport is driven by the electrochemical potential of Na+ in this organism. PMID- 4030699 TI - Patterns of attrition for psychosocial and pharmacologic treatments of depression. AB - Patient characteristics associated with early termination from psychosocial and pharmacologic treatments of depression were delineated. Patients were 125 female primary nonbipolar depressives randomly assigned to 12 weeks of protocol treatment in one of four conditions: social skills training plus placebo; short term psychotherapy plus placebo; amitriptyline alone; and social skills training plus amitriptyline. Results indicated that premature terminators from pharmacotherapy tended to be mildly depressed and intolerant of medication side effects. In contrast, dropouts from psychosocial treatment were more severely depressed and dissatisfied with the lack of early response which often accompanies interventions of this type. These findings may support the use of short-term psychosocial approaches in lieu of pharmacotherapy in mild nonendogenous depressions. However, antidepressant medication, either alone or in conjunction with psychosocial treatment, should continue to be considered the treatment of choice in more severely depressed melancholic patients. PMID- 4030700 TI - Posttraumatic flashbacks, dream disturbances, and mental imagery. AB - Posttraumatic flashbacks or revisualizations are a well-established symptom of posttraumatic stress disorder (PTSD). These episodes are capable of precipitating accidents. In this two-part study, the results of a previous pilot study which demonstrated an association between flashbacks and dream disturbances are confirmed. Such an association may be of use in prediction which PTSD patients are vulnerable to flashbacks. In addition, a comparison is made between flashback PTSD patients and other PTSD patients using the Impact of Event Scale. Flashback patients reported more frequent intrusive items on average and, specifically, more frequent daytime mental imagery. The implications of these findings are discussed. PMID- 4030701 TI - Combat-related flashbacks in posttraumatic stress disorder: phenomenology and similarity to panic attacks. AB - Combat veterans (N = 25) with posttraumatic stress disorder had flashbacks related to their combat stressors, which included major losses and exposure to danger. Certain affects, loud noises, fatigue, and personal stress tended to precipitate flashback episodes. Flashbacks began a year or more after exposure to combat in 50% of patients; 56% of patients experienced daily flashbacks. Flashback phenomenology met DSM-III criteria for panic attacks. The similarity of flashbacks to panic attacks suggests treatment trials with monoamine oxidase inhibitors or imipramine for these selected symptoms. PMID- 4030702 TI - Olfactory precipitants of flashbacks in posttraumatic stress disorder: case reports. AB - The phenomenon of vivid flashbacks elicited by olfactory stimuli is described in two combat veterans with posttraumatic stress disorder (PTSD). Although many sensory and cognitive cues can elicit flashback phenomena, smell has distinctive characteristics that make evocation of vivid olfactory memories particularly likely. It is recommended that clinicians inquire specifically about olfactory precipitants when evaluating combat veterans disabled by PTSD flashbacks. PMID- 4030703 TI - Concurrent depression and dementia: implications for diagnosis and treatment. AB - The need to distinguish between depression and dementia is well recognized and has been much discussed, but the coexistence of the two illnesses has received less attention. Three cases are presented which corroborate previous reports of the coexistence of dementia and depression but also raise other issues. It is suggested that this diagnosis should not be viewed as an "either/or" decision, but that each diagnosis should be considered independently. The cases illustrate that the type of depression present may vary and that an accurate assessment of dementia may be possible only after depressive symptoms have abated. Other issues encountered in this clinical situation are discussed. PMID- 4030704 TI - Carbamazepine in mixed frontal lobe and psychiatric disorders. AB - Carbamazepine was given to five patients with mixed frontal lobe disease and a variety of primary psychiatric disorders. All five patients benefited significantly. A decrease in affective lability was the most consistent result. Carbamazepine may be an alternative to chronic high-dose neuroleptic therapy in these patients. PMID- 4030705 TI - Auditory hallucinosis and atypical tic disorder: case reports. AB - Two patients with tic disorders and intermediate hallucinatory experiences are described. It is suggested that clinicians evaluating patients with tic disorders may wish to inquire routinely about unusual auditory experiences. Further research will be necessary to determine the implications of these experiences among children with tic disorders. PMID- 4030706 TI - Partial resolution of ranitidine-associated delirium with physostigmine: case report. AB - A healthy 25-year-old woman experienced probable ranitidine-induced confusion that partially resolved with intravenous physostigmine. The only known prior report of confusion associated with this relatively new agent was in a severely ill 86-year-old woman. Clinicians should be alert for mental status changes with ranitidine and consider a trial of physostigmine when indicated. PMID- 4030707 TI - Psychiatric patients at high risk for rhabdomyolysis. PMID- 4030708 TI - Peripheral blood lymphocyte numbers, lymphocyte proliferative responses in vitro, and serum immunoglobulins in regular hemapheresis donors. AB - Selected tests of lymphoid function were used to screen a population of volunteer hemapheresis donors. Testing included: 1) absolute lymphocyte numbers, and percentage of T-cell, B-cell, and mononuclear phagocytes, 2) serum immunoglobulins, and, 3) in vitro proliferative responses to lectin mitogens (phytohemagglutinin, concanavalin A, and pokeweed mitogen), soluble antigens (staphylococcal filtrate, candida, and streptococcal varidase), and cell-bound alloantigens (mixed lymphocyte culture). A control population of first-time plateletpheresis donors was examined similarly. Regular donors manifested a small but statistically significant decrease in absolute lymphocyte counts (p less than 0.02), and IgM (p less than 0.02) compared to controls. Leukapheresis donors also manifested significant decreases in percentage of T cells (p less than 0.02). These findings are qualitatively similar to changes reported following intensive lymphocytapheresis and indicate the need for conservative policies regarding donation frequency in hemapheresis programs. PMID- 4030709 TI - The clinical effectiveness and safety of chronic plasmapheresis in patients with primary biliary cirrhosis. AB - Primary biliary cirrhosis (PBC) is a chronic nonsuppurative, destructive cholangitis, whose etiology is unknown. Morbidity arises early from pruritus and later from hypercholesterolemia with xanthoma formation. Therapy is supportive and directed at the complications of cholestasis. Plasmapheresis has been reported to benefit patients with hyperlipidemia and PBC; thus a pilot study of plasmapheresis utilizing the Haemonetics Model 30 with replacement by albumin and saline was conducted. Five patients (four female and one male) with a mean age of 43 (range 29-58) and a mean duration of illness of 9.5 years (range 6-21) with marked jaundice, xanthomas, xanthelasma, hepatomegaly, fatigability, anorexia, and pruritus, as well as mild nausea were studied. Peripheral neuropathy was present in two patients. Two patients had splenomegaly. Two patients had an associated Sjogren syndrome. All patients had high serum bilirubin, alkaline phosphatase, and cholesterol levels and mild elevations in aspartate amino transferase and alanine amino transferase activities. Immune complexes measured in four patients were present. Antimitochondrial antibody titers were significant in all patients. Patients underwent a mean of 63 plasmapheresis procedures over a mean of 112 weeks removing a mean of 94.7 liters of plasma. No serious toxicity was seen. All patients showed a reduction in pruritus, xanthomas, xanthelasmas, and serum cholesterol values. The two patients who had evidence of Sjogren syndrome noted subjective improvement. All patients who had fatigue, anorexia and nausea also noted moderate improvement. There was no change in hepatomegaly or splenomegaly in patients demonstrating such organomegaly. Liver function did not change significantly. Overall, four patients had improvement in their condition and one patient achieved stability.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4030710 TI - Continuous-flow techniques for platelet concentrate collection: a step toward standardization and yield predictability. AB - This study chronicles leukocyte- and erythrocyte-depleted platelet concentrate collection by a dual stage channel in which three variables: 1) donor peripheral blood platelet concentration, 2) total blood processed, and 3) collection volume were statistically correlated with platelet yield as determined by a multiple regression analysis of single variables. Platelet concentration in the final yield was related to donor precount and collection rate, and could be varied as indicated for individual applications. Total blood processed was established by procedure time, which in turn was defined by citrate-induced calcium changes in the donor. Reduction in peripheral blood platelet concentration averaged 24% for a mean platelet yield of 3.8 X 10(11). An average of 40% of transfused platelet concentrates were recovered in recipient peripheral blood 1 hr posttransfusion and were hemostatically effective, as determined by correction of bleeding time. Platelet yields and patient response were sustained during current collection procedures, verifying the principles described during the investigative period. PMID- 4030711 TI - Plasma exchange in six patients with advanced cancers of the head and neck. AB - Six patients with advanced squamous cell cancers of the head and neck, with serum IgA greater than or equal to 400 mg/dl and IgE less than or equal to 1000 IU/ml, underwent a trial of six 2-liter plasma exchanges over a 2-3-week period. Disease progressed in patients 1, 2, and 4, who died on days 44, 72, and 159. The tumor in patients 3 and 6 regressed significantly, repeatedly in patient 3 over each of four courses of apheresis. Tumor recurred in both patients after cessation of treatment, and they died at days 420 and 79. Patient 5, with inoperable disease, received full-dose radiotherapy immediately following the course of apheresis, and showed complete response in the primary lesion and a major response in the extensive lymph node metastases, dying on day 421 of apparently unrelated causes. Serum IgE in the three patients experiencing tumor regression rose paradoxically during plasmapheresis. Only patient 3 had an elevated level of soluble E-receptor suppressor factor prepheresis; the serum of patient 6 was lymphocytotoxic prepheresis but this activity decreased or disappeared during each of the exchanges studied. Controlled trials are now indicated. PMID- 4030712 TI - Platelet collection using the IBM 2997 cell separator. AB - Platelets were collected using the dual-channel module on the IBM 2997 Blood Fraction Separator. We carried out 320 procedures to harvest platelets for therapeutic purposes and yielded 5.1 +/- 1.5 X 10(11) platelets (mean +/- SD). Infusion into previously unsensitized recipients with hypomegakaryocytic thrombocytopenia achieved increments at 1 hr of 19 +/- 7.3 X 10(9)/liter/m2 (mean +/- SD) and at 24 hr of 15 +/- 6.3 X 10(9)/liter/m2. The only consistent donor reaction was mild hypocalcaemia, easily corrected by calcium gluconate infusion. Changes in donor packed-cell volume and white cell count were not statistically altered (p greater than 0.05) but donor platelet counts fell from 216 +/- 43.1 X 10(9)/liter to 162.5 +2- 41.7 X 10(9)/liter (mean +/- SD) (p less than 0.01). Additional plateletphereses were carried out in seven normal volunteers, using the same technique, in order that the function of the harvested platelets could be studied. Following radiochromium labelling and reinfusion into the same donors, normal in vivo recoveries were obtained at 10 min (59.4 +/- 3.4%; mean +/ SD) and platelet mean life span was also normal (218 +/- 12 hr; mean +/- SD). Furthermore, in vitro platelet factor III availability and aggregation patterns of the harvested platelets did not differ from control values and their ultrastructural appearance was normal. PMID- 4030713 TI - Calcium binding to troponin C and troponin: effects of Mg2+, ionic strength and pH. AB - Calcium binding to troponin C and troponin was examined by a metallochromic indicator method under various conditions to obtain a further understanding of the regulatory roles of these proteins in muscle contraction. Troponin C has four Ca binding sites, of which 2 sites have a high affinity of 4.5 X 10(6) M-1 for Ca2+ and the other 2 sites have a low affinity of 6.4 X 10(4) M-1 in a reaction medium consisting of 100 mM KCl, 20 mM MOPS-KOH pH 6.80 and 0.13 mM tetramethylmurexide at 20 degrees C. Magnesium also binds competitively to both the high and low affinity sites: the apparent binding constants are 1,000 M-1 and 520 M-1, respectively. Contrary to the claim by Potter and Gergely (J. Biol. Chem. 250, 4628-4633, 1975), the low affinity sites are not specific only for Ca2+. The high and low affinity sites of troponin C showed different dependence on the ionic strength: the high affinity sites were similar to GEDTA, while the low affinity sites were similar to calmodulin, which has a steeper ionic strength dependence than GEDTA. Ca binding to troponin C was not affected by change of pH between 6.5 and 7.2. Troponin I enhanced the apparent affinity of troponin C for Ca2+ to a value similar to that for troponin. Trifluoperazine also increased Ca binding to troponin C. Troponin has four Ca binding sites as does troponin C, but the affinities are so high that the precise analysis was difficult by this method. The apparent binding constants for Ca2+ and Mg2+ were determined to be 3.5 X 10(6) M-1 and 440 M-1, respectively, for low affinity sites under the same conditions as for troponin C, being independent of change in pH between 6.5 and 7.2. The competitive binding of Mg2+ to the low affinity sites of troponin is consistent with the results of Kohama (J. Biochem. 88, 591-599, 1980). The estimate for the high affinity sites is compatible with the reported results. PMID- 4030714 TI - Paratropomyosin: a new myofibrillar protein that modifies the actin-myosin interaction in postrigor skeletal muscle. I. Preparation and characterization. AB - A protein component which is released from skeletal-muscle myofibrils on the treatment with Ca2+ at concentrations above 10(-5) M and modifies the actin myosin interaction was purified by a method involving column chromatography on Sephadex G-200 and DEAE-cellulose in succession. Although this protein resembles tropomyosin in some physicochemical properties, it has the same chain weight of 34,000 as the alpha-component of tropomyosin on SDS-polyacrylamide gel electrophoresis, and differed from tropomyosin not only in the amino acid composition but also in prolonging the clearing phase of superprecipitation of reconstituted actomyosin. We therefore concluded that this protein is a new myofibrillar one, and termed it "paratropomyosin." In postrigor muscle, it seems likely that paratropomyosin is released from its original locus with an increased concentration of Ca2+, and that it weakens rigor linkages formed between actin and myosin. PMID- 4030715 TI - Difference in enzymatic properties between alpha-thrombin-staphylocoagulase complex and free alpha-thrombin. AB - The steady-state kinetic parameters of human alpha-thrombin and the alpha thrombin-staphylocoagulase complex as to the chromogenic substrate, H-D-Phe-Pip Arg-p-nitroanilide (S-2238), were determined. At pH 8.0 and 37 degrees C, the Km values for alpha-thrombin and the complex for S-2238 were 7.9 microM and 7.7 microM, respectively. The kcat of this amidase reaction catalyzed by the complex was 127 s-1, which had apparently decreased from the kcat of 197 s-1 determined for free alpha-thrombin. This difference in the kinetic parameter between alpha thrombin and the complex was also observed using the fluorogenic substrate, Boc Val-Pro-Arg-4-methylcoumaryl-7-amide. Moreover, the fibrinogen clotting activity of the alpha-thrombin-staphylocoagulase complex was less than half that of alpha thrombin, suggesting that the alpha-thrombin active site in the complex is different in catalytic ability from that of free alpha-thrombin. Other evidence supporting this view was as follows: The alpha-thrombin-staphylocoagulase complex is insensitive to antithrombin III, the complex shows much weaker binding to hirudin, as compared to free alpha-thrombin, and the amidase pH-profiles of the complex and free alpha-thrombin differ from each other. These results indicate that the microenvironment of the active site of alpha-thrombin is significantly altered by the complex formation with staphylocoagulase. PMID- 4030716 TI - A common linkage saccharide unit between teichoic acids and peptidoglycan in cell walls of Bacillus coagulans. AB - Teichoic acid-glycopeptide complexes were isolated from lysozyme digests of the cell walls of Bacillus coagulans AHU 1631, AHU 1634, and AHU 1638, and the structure of the teichoic acid moieties and their linkage regions was studied. On treatment with hydrogen fluoride, each of the complexes gave a hexosamine containing disaccharide, which was identified to be glucosyl(beta 1----4)N acetylglucosamine, in addition to dephosphorylated repeating units of the teichoic acids, namely, galactosyl(alpha 1----2)glycerol and either galactosyl(alpha 1----2)[glucosyl(alpha 1----1/3)]glycerol (AHU 1638) or galactosyl(alpha 1----2)[glucosyl(beta 1----1/3)]glycerol (AHU 1631 and AHU 1634). From the results of Smith degradation, methylation analysis, and partial acid hydrolysis, the teichoic acids from these strains seem to have the same backbone chains composed of galactosyl(alpha 1----2)glycerol phosphate units joined by phosphodiester bonds at C-6 of the galactose residues. The presence of the disaccharide, glucosyl(beta 1----4)N-acetylglucosamine, in the linkage regions between teichoic acids and peptidoglycan was confirmed by the isolation of a disaccharide-linked glycopeptide fragment from each complex after treatment with mild alkali and of a teichoic acid-linked saccharide from each cell wall preparation after treatment with mild acid. Thus, it is concluded that despite structural differences in the glycosidic branches, the teichoic acids in the cell walls of the three strains are linked to peptidoglycan through a common linkage saccharide, glucosyl (beta 1----4) N-acetylglucosamine. PMID- 4030717 TI - Stimulation by glucocorticoids of the differentiated phenotype of chondrocytes and the proliferation of rabbit costal chondrocytes in culture. AB - Hydrocortisone stimulated glycosaminoglycan (GAG) synthesis, a characteristic of the cartilage phenotype, of rabbit costal chondrocytes in confluent quiescent culture, as judged by the incorporations of [35S]sulfate and [3H]glucosamine. Hydrocortisone also stimulated incorporation of [3H]serine into proteoglycan. The stimulation of GAG synthesis by hydrocortisone was dose-dependent and maximal at a physiological concentration of 10(-7) M. Hydrocortisone also stimulated GAG synthesis in cultures in the log-phase of growth. In this case, its maximal effect was observed at a concentration of 10(-6) M. The magnitude of the increase of GAG synthesis in response to hydrocortisone was larger in confluent culture than in log-phase cultures. Hydrocortisone stimulated DNA synthesis dose dependently, and its effect was observable at a physiological concentration. However, no stimulation of DNA synthesis by hydrocortisone was observed in serum free medium, in contrast to that of GAG synthesis. Hydrocortisone also increased protein synthesis and the cell number. Dexamethasone also stimulated the syntheses of both GAG and DNA. These results show that glucocorticoids stimulated both the differentiated phenotype of chondrocytes and the proliferation of rabbit costal chondrocytes in culture. Moreover, the effect of glucocorticoids was primarily on the differentiated phenotype of chondrocytes and its effect on proliferation was permissive. PMID- 4030718 TI - Denaturation of bovine liver glutamate dehydrogenase by guanidine hydrochloride. Correlation between enzymatic activity and molecular state. AB - Bovine liver glutamate dehydrogenase (GDH), a hexameric enzyme, undergoes subunit dissociation, denaturation, and inactivation in the presence of guanidine hydrochloride (GdnHCl), depending on the denaturant concentration. The correlation between the enzymatic activity and the molecular state of GDH, and the reconstitution of native hexamer from subunits after the removal of GdnHCl were examined by measuring the enzymatic activity and CD spectrum in the far ultraviolet region. It was found that only the hexameric form of GDH has enzymatic activity, and the reconstitution of the hexamer with full enzymatic activity from the trimeric form which has native polypeptide chain structure can be achieved by the removal of GdnHCl. On the other hand, the recovery of enzymatic activity from the dissociated form in more concentrated GdnHCl solution where unfolding of the polypeptide chain takes place showed an exponential decrease with increasing incubation time in the GdnHCl solution. The time constant for the decay of enzymatic activity with respect to the incubation time was almost the same as that for unfolding of the polypeptide chain (followed by CD spectroscopy). It is suggested on the basis of these experimental results that the failure of reconstitution of GDH hexamer from subunits produced at high denaturant concentration is due to failure in the refolding of the unfolded subunit to the correct three-dimensional structure of the polypeptide chain rather than in the reassociation process from subunits. PMID- 4030719 TI - Purification and some properties of phosphoenolpyruvate carboxylase from Brevibacterium flavum and its aspartate-overproducing mutant. AB - Phosphoenolpyruvate (PEP) carboxylases (PC) were purified from a wild strain and an aspartate-producing mutant of Brevibacterium flavum to electrophoretic homogeneity. The molecular weights of the enzymes were determined to be 4.1 X 10(5) by the gel-filtration technique. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the enzyme gave only one protein band with a molecular weight of 1.07 X 10(5). The enzyme was labile and stabilized by substrate PEP, activators, metallic cofactors, an allosteric inhibitor and ammonium sulfate. The mechanism for the PC reaction was rapid equilibrium random Bi Bi with a dead end complex, enzyme-bicarbonate-Pi. The KmS for PEP and bicarbonate were 2.5 and 0.63 mM, respectively, and the apparent KmS were not affected by the secondary substrate concentrations. Dissociation constants for Pi of enzyme-Pi and the dead end complex were 5.0 and 16 mM, respectively. Aspartate inhibition was completely competitive with both the substrates, PEP and bicarbonate, with an inhibitor constant of 0.044 mM. An activator, acetyl-CoA, did not alter the apparent Km for bicarbonate but decreased that for PEP. The activator constants for the enzyme PEP complex and free enzyme were 6.3 and 40 microM, respectively. Double reciprocal plots of reaction rate against PEP concentration were not linear at lower PEP concentrations. Hill coefficients for PEP were 1.6 in the absence of any effectors, 1.0 in the presence of acetyl-CoA, and 2.3 in the presence of aspartate. As to the mutant enzyme, only the inhibitor constant for aspartate was increased, being 0.18 mM, but other constants, coefficients, as described above, and specific activity were almost the same as those of the wild-type enzyme. PMID- 4030720 TI - Splice-site signals of mRNA precursors as revealed by computer search. Site specific mutagenesis and thalassemia. AB - Many eukaryotic genes are interrupted by introns, which are removed from mRNA precursors by the RNA splicing mechanism. Although nucleotide sequences around splice sites have considerable homology among various genes, exact splice-site signals are unknown. Previously, applying the computer searching method to primary nucleotide sequences of various genes, we studied what kinds of patterns are the necessary and sufficient sequences for recognition of the 5'-slice site (donor site). We proposed that four common patterns, AG/GTA, /GTAAGT, RG/GTGAG, and AG/GTXXGT, where R = A or G and X = A, T, G, or C, are often used as such signals. In the present paper, we examined a number of experimental results on site-specific mutagenesis around donor sites and on alpha- and beta-thalassemia in globin genes, and found that the above four common patterns could explain almost all of those results. PMID- 4030721 TI - Energy-independent protection of the oxidative phosphorylation capacity of mitochondria against anoxic damage by ATP and its non-metabolizable analogs. AB - Preservation of the oxidative phosphorylation capacity of mitochondria by addition of ATP under anaerobic conditions was analyzed by use of non metabolizable adenine nucleotide analogs. The capacity was well preserved in the presence of ATP and did not require the hydrolysis of ATP, since ATP analogs, such as beta, gamma-methylene adenosine triphosphate (AMPPCP), alpha, beta methylene adenosine triphosphate (AMPCPP), and adenylyl imidodiphosphate (AMPPNP), were as effective as ATP. These analogs were incorporated into mitochondria through ATP/ADP translocase to maintain the original level of total adenine nucleotides in the mitochondria. ADP apparently had the same effect as ATP, but its effect was shown to be due to ATP generated from it by adenylate kinase in mitochondria. An analog of ADP, alpha, beta-methylene adenosine diphosphate (AMPCP), which was found to be a substrate of the translocase but not of adenylate kinase, could not replace ADP or ATP. From these results, it was concluded that the oxidative phosphorylation capacity of mitochondria was maintained by ATP, but not ADP, through a process not requiring energy. PMID- 4030722 TI - Induction of peroxisomal beta-oxidation enzymes in primary cultured rat hepatocytes by clofibric acid. AB - Rat hepatocytes were cultured for 72 h with or without the addition of 0.5 mM clofibric acid. The activities of individual enzymes of the peroxisomal beta oxidation pathway (acyl-CoA oxidase, enoyl-CoA hydratase-3-hydroxyacyl-CoA dehydrogenase bifunctional protein, and 3-ketoacyl-CoA thiolase) decreased in the control culture, but markedly increased synchronously in the clofibric acid treated culture. The levels of mRNAs coding for these enzymes and the rates of synthesis of the enzymes were also elevated in the clofibric acid-treated culture, although no proportional relationship was observed between the time dependent changes of these parameters. The increase in mRNAs was much higher than the increase in the rate of synthesis of the enzymes. The activity of catalase, its mRNA level and the rate of its synthesis were slightly affected. The effects of clofibric acid on the peroxisomal beta-oxidation enzymes and catalase in primary cultured hepatocytes were very similar to those observed in vivo. These results, therefore, suggest that primary culture of hepatocytes should provide a useful means for investigating the mechanism of induction of peroxisomal enzymes and the mechanism of action of peroxisome proliferators. PMID- 4030723 TI - Purification and characterization of NADH oxidase from a strain of Leuconostoc mesenteroides. AB - An NADH oxidase was purified to homogeneity from Leuconostoc mesenteroides with a specific activity 100-fold higher than that of the crude extract. The purified NADH oxidase was an acidic protein having an S0 20,W of 5.49S and a molecular weight of 104,000, consisting of a dimer with 53,000 subunit size. The enzyme could use O2, dichlorophenolindophenol and methylene blue as oxidants, but not H2O2, cytochrome c, or ferricyanide. The physiological substrate was beta-NADH (Km = 0.12 mM) with O2 as the oxidant, probably forming H2O, rather than H2O2. Activity toward alpha-NADH was observed (Km = 0.14 mM), but the maximum velocity was 3 orders of magnitude lower than that with beta-NADH. alpha-NADPH and beta NADPH were inert for the reaction. The enzyme showed a flavoprotein absorption spectrum with maxima at 273, 379, and 450 nm with a shoulder at 465 nm: the absorption at 450-465 nm disappeared on adding excess NADH or hydrosulfite. One mol of the holoenzyme contained approximately 2 mol of FAD. The apoenzyme was obtained by treatment with EDTA-KBr solution and could be reconstituted partially by adding FAD, but not riboflavin or FMN. The maximum activity of the reaction was observed at pH 6.5 in a temperature range of 35-45 degrees C. The activation energy was estimated to be 3.77 kcal/mol. The enzyme was inhibited by SH reagents, quinacrine, quinine, and Cu2+, but not by EDTA. Adenine and its nucleoside 5'-di- and triphosphates showed competitive inhibitions, while various metabolites, such as H2O2, FDP, acetyl phosphate, lactate, ethanol, and acetate, did not affect the reaction. PMID- 4030724 TI - Further study on polyamines in primitive unicellular eukaryotic algae. AB - The possible usefulness of polyamines as chemotaxonomic markers has been investigated in eukaryotic algae. Polyamines were analyzed in 12 species of primitive unicellular eukaryotic algae including some anomalous species. Norspermidine and norspermine in addition to putrescine and spermidine are widely distributed in most unicellular species of the algae. However, neither norspermidine nor norspermine was found in the taxonomically conflicting algae, Cyanophora and Glaucocystis, which contain cyanellae, or in a primitive red alga, Porphyridium. A thermoacidophilic eukaryotic alga, Cyanidium, is rich in both norspermidine and norspermine. Appreciable amounts of spermine and sym homospermidine were detected only in the species belonging to the Rhodophyta (red algae). PMID- 4030725 TI - The binding of a thyroid hormone metabolite, 3-monoiodo-L-thyronine, to bovine serum albumin as measured by circular dichroism. AB - The interaction between a thyroid hormone metabolite, 3-monoiodo-L-thyronine (3 T1) and bovine serum albumin (BSA) was investigated by using the CD method. An enhanced CD band was observed at the absorption wavelength region of 3-T1 around 293 nm suggesting the binding of 3-T1 to the BSA molecule. The ellipticity at 293 nm was measured at various molar ratios of 3-T1 to BSA, and the apparent binding constant and the maximum number of binding sites could be estimated as Kapp = 8.85 +/- 1.07 X 10(4) M-1 and n = 23.8 +/- 0.9 respectively. The CD of a mixture of BSA, 3-T1 and thyroxine (T4) was also studied at various pH's. The pH profile of the two characteristic CD bands at 293 nm and 320 nm, attributed to bound 3-T1 and T4, suggested that the optimum binding condition of 3-T1 was attained at alkaline pH of around 9, while that of T4 was attained over a wide pH range between 5-10. A significant role of the ionized 4'-hydroxyl group of 3-T1 in the binding reaction with BSA is also suggested. PMID- 4030726 TI - Aspartate aminotransferase isozymes from rabbit liver. Purification and properties. AB - Cytosolic and mitochondrial isozymes of aspartate aminotransferase (L-aspartate:2 oxoglutarate aminotransferase [EC 2.6.1.1] ) were purified to homogeneity from rabbit liver. The rabbit liver isozymes were closely similar to the corresponding isozymes from other sources, including human heart, pig heart, chicken heart, and rat liver, in their molecular weights, absorption spectra, amino acid compositions, isoelectric points, and Michaelis constants for the substrates. The NH2-terminal amino acid sequences of rabbit liver isozymes were identified up to 30 residues, and showed some differences from those of the corresponding isozymes obtained from other animals so far studied. PMID- 4030727 TI - Appearance of new hepatic glucocorticoid binding proteins under various stressful conditions: relation to endogenous glucocorticoid secretion. AB - When rats were subjected to the stress of burns, tumors, or partial hepatectomy, a notable new peak of glucocorticoid binding protein appeared on DEAE-cellulose chromatography. This peak accompanied the original peak, which was the only dominant peak in intact rats. The appearance of the new binding protein was concomitant with a high rise in serum corticosterone levels. The new peak was eluted with 0.12-0.14 M NaCl and another, small new peak with 0.02-0.03 M NaCl, while the original peak of intact rats was eluted with 0.05-0.08 M NaCl. In rats adrenalectomized prior to the stress, the new peaks did not appear. To mimic these stressful conditions which provoked a burst of endogenous glucocorticoid, rats were administered with an exogenous high dose of dexamethasone (100 micrograms/100 g B.W.) in vivo. The new peak eluted with 0.12-0.14 M NaCl was again observed and was more dominant in the hormone-treated rats than the stressed rats. These three peaks eluted with 0.02-0.03 M, 0.05-0.08 M, and 0.12 0.14 M NaCl are called here Peak A, B, and C, respectively. This is the first demonstration of the effect of physiological changes in serum levels of glucocorticoid hormone on the nature of glucocorticoid binding protein by DEAE cellulose chromatography. PMID- 4030728 TI - Selective separation of tryptophan-containing peptides via hydrophobic modification with 2-nitro-4-carboxyphenylsulfenyl chloride. AB - Selective separation of tryptophan-containing peptides has been attempted using 2 nitro-4-carboxyphenylsulfenyl chloride (NCps)-C1 as a reagent for hydrophobic modification of tryptophan. S-Carboxymethylated proteins were modified with NCps C1 in 70% acetic acid and digested with TPCK-trypsin, and the digests were fractionated, directly or after partial fractionation on a Sephadex G-25 column, by high performance liquid chromatography using a reverse phase column. The tryptophan-containing peptides from the tryptic digests of S-carboxymethylated hen-egg white lysozyme and Trimeresurus flavoviridis phospholipase A2 were thus selectively separated and the amino acid sequences were determined, showing the validity of the method. The phenylthiohydantoin derivative of 2-(2'-nitro-4' carboxyphenylthio)-L-tryptophan was synthesized and its spectroscopic and chromatographic properties determined, enabling us to identify the derivative on Edman sequencing. PMID- 4030729 TI - Release of hepatic mitochondrial ornithine transcarbamylase into the circulation in D-galactosamine-treated rats. Identification of serum ornithine transcarbamylase as the intact form of the mitochondrial enzyme. AB - A single injection of D-galactosamine into rats caused acute liver cell injury, and the activity of ornithine transcarbamylase in the serum increased about 600 fold as compared with that in the normal serum. Some properties of the serum enzyme from galactosamine-treated rats have been studied together with those of the mitochondrial enzyme in liver. Both the enzyme activities gave similar pH profiles, showing an optimum of pH 8.5. Apparent Km values of the serum enzyme for ornithine under the standard conditions at pH 7.4 and pH 7.7 were 1.59 mM and 0.94 mM, respectively, and those of the mitochondrial enzyme were 1.69 mM and 0.97 mM, respectively. The Km value of the serum enzyme for carbamyl phosphate was 0.34 mM, which is similar to that of the mitochondrial enzyme. The mitochondrial enzyme was purified 78-fold to homogeneity with a 45% yield by ammonium sulfate fractionation, heat treatment, 2nd ammonium sulfate fractionation, and phenyl-Sepharose CL-4B and CM-Sephadex C-50 column chromatographies. The specific activity of the purified enzyme was 282 mumol of citrulline formed per mg of protein per min at 37 degrees C. The mitochondrial and serum enzymes have a molecular weight of 115,000 as determined by Sephacryl S 300 gel filtration. Antibody specific for the mitochondrial enzyme was raised, and the immunological properties of the serum enzyme were examined. In immunoinhibition experiments, a decrease of the serum enzyme activity as well as the mitochondrial enzyme was observed on increasing the amount of the antibody. PMID- 4030730 TI - A comparative study of tropomyosin from vertebrate ventricles. AB - A comparative study of vertebrate ventricle tropomyosin has been carried out from the viewpoint of molecular evolution. The ventricles containing one-component tropomyosin were generally known, and in this paper those containing two components were also found in 8 species among mammals, reptiles, amphibia, and fish, but not among birds. The two components were concluded to be authentic tropomyosin and not artifacts since they showed lower electrophoretic mobilities in the presence of urea, and they were precipitated at pH 4.5 and bound to F actin. Studies on cysteine contents and cyanogen bromide cleavage peptide patterns revealed that the characteristics of the two tropomyosin components from pig, turtle, amphibia and carp ventricles varied increasingly in that order from typical alpha- and beta-characteristics as seen in rabbit skeletal muscle tropomyosin. The single component of chicken ventricle tropomyosin showed alpha component characteristics in its electrophoretic mobility and cysteine content, and beta component characteristics in cyanogen bromide cleavage peptide pattern. The two components of carp ventricle tropomyosin seemed to be the most primitive, having two cysteine residues per molecule and a cyanogen bromide cleavage peptide pattern different from those of the two components of rabbit skeletal muscle. PMID- 4030731 TI - A simple and rapid procedure for high-yield isolation of essentially undegraded free and membrane-bound polysomes from rat liver. AB - A procedure is described for the preparation of free and membrane-bound polysomes from rat liver. The procedure involves: differential centrifugation of liver homogenate to separate free and membrane-bound polysomes; treatment of the membrane-bound polysome fraction with a detergent to release bound polysomes from membranes; and magnesium precipitation of both classes of polysomes. Free and bound polysomes prepared in this manner were essentially undegraded and highly active in cell-free protein synthesis. The recovery of polysomes was nearly quantitative and the distribution between the free and membrane-bound state was 41 and 59%, respectively. Polypeptides synthesized in vitro by the free and membrane-bound polysomes were quite different. The majority (81-84%) of mRNA activities of two secretory proteins (albumin and transferrin) were recovered in the membrane-bound polysomes, whereas the majority (81-85%) of mRNA activities of two cytosolic [aldolase B, EC 4.1.2.13, and argininosuccinate synthetase, EC 6.3.4.5], one mitochondrial [ornithine carbamoyltransferase, EC 2.1.3.3] and one peroxisomal [catalase, EC 1.11.1.6] proteins were recovered in the free polysomes. A polysome class synthesizing ornithine carbamoyltransferase was purified 42-fold from the free polysomes by immunoprecipitation. The procedure is rapid (4-5 h) and reproducible, and provides a nearly quantitative means of separating the two classes of polysomes. PMID- 4030732 TI - Role of alkaline phosphatase in phosphate uptake into brush border membrane vesicles from human intestinal mucosa. AB - In order to elucidate the physiological function of intestinal alkaline phosphatase, the characteristics of human intestinal alkaline phosphatase bound to brush border membrane vesicles were compared under optimal and physiological pHs. The Km value of this enzyme towards p-nitrophenylphosphate at the physiological pH was lower than that at the optimal pH. At the physiological pH, phosphate, arsenate and vanadate competitively inhibited the alkaline phosphatase activity, as they did at optimal pH, and the K1 values of these inhibitors at the physiological pH were also lower than those at the optimal pH. The effects of various inhibitors and antibody to human intestinal alkaline phosphatase on phosphate uptake into brush border membrane vesicles were investigated. The results indicated that phosphate uptake was affected by various inhibitors and the antibody to human intestinal alkaline phosphatase, but L-homoarginine, levamisole, and ouabain had no effect. From the above findings, it is strongly suggested that human intestinal alkaline phosphatase may function as a phosphate binding protein at low phosphate concentrations under physiological conditions. PMID- 4030733 TI - Proline iminopeptidase from Bacillus coagulans: purification and enzymatic properties. AB - Proline iminopeptidase [EC 3.4.11.5] was purified about 2,700-fold from cell-free extract of Bacillus coagulans by a series of column chromatographies on DEAE Toyopearl, PCMB-T-Sepharose, and hydroxyapatite, and gel filtration on Sephadex G 150. The purified enzyme was homogeneous as judged by disc gel electrophoresis. The enzyme was most active at pH 7.3 with Pro-beta-naphthylamide (Pro-2-NNap) as the substrate, and hydrolyzed Pro-X (X = amino acid including proline, peptide, amide, and arylamide) bonds when the proline residue was at the amino terminus. Pro-D-amino acid bonds were also susceptible to the enzyme. The enzyme was completely inhibited by p-chloromercuribenzoate (PCMB) and partially by proline but not by metal chelators, diisopropylphosphorofluoridate (DFP), or phenylmethanesulfonyl fluoride (PMSF). The enzyme inactivated with PCMB was reactivated by incubation with 2-mercaptoethanol. These results and the chromatographic profile on PCMB-T-Sepharose suggest that the enzyme is a sulfhydryl enzyme. The isoelectric point of the enzyme was 4.0, and the molecular weight of the enzyme was estimated to be 40,000 by gel filtration on Sephadex G 100 and 35,000 by sodium dodecyl sulfate (SDS) gel electrophoresis, indicating that the enzyme exists as a monomer. PMID- 4030734 TI - Affinity chromatography of urokinase on an agarose derivative coupled with pyroglutamyl-lysyl-leucyl-argininal. AB - Pyroglutamyl-lysyl-leucyl-argininal (Pyr-Lys-Leu-Argal) immobilized on gel matrix through the epsilon-amino group of its lysine residue was shown to be an efficient biospecific affinity adsorbent for purification of urokinase. Pyr-Lys Leu-Argal dibutylacetal, a precursor of this immobilized ligand, was synthesized by a fragment condensation procedure, in which one of the thermolysin-digestion products of leupeptin dibutylacetal, H-Leu-Argal dibutylacetal, was used as a key intermediate. The precursor was coupled to CH-Sepharose 4B with the aid of a water-soluble carbodiimide, and its acetal protecting group was then removed by mild acid treatment to free the essential aldehyde function. The Sepharose derivative thus prepared was shown to adsorb urokinase selectively and effectively from a crude human urine preparation at neutral pH and to release the bound enzyme under mild acidic conditions. The present technique afforded a highly purified urokinase preparation abundant in the high-molecular form with 90% recovery. The complex formed between urokinase and the immobilized ligand was found to have a dissociation constant of about 2 X 10(-4)M. PMID- 4030735 TI - ATP hydrolysis coupled to microtubule sliding in sea-urchin sperm flagella. AB - Using sea urchin (Hemicentrotus pulcherimus) sperm flagella, ATP hydrolysis coupled to sliding movement of microtubules was investigated. Flagellar axonemes were pretreated with trypsin and the microtubules induced to slide by addition of ATP (50-1,000 microM) at 0-20 degrees C. Motion-dependent hydrolysis of ATP was observed immediately after the addition of ATP, the rate of which was higher than that of steady state hydrolysis in axonemes without trypsin-treatment, or after complete disintegration. The rate of hydrolysis of ATP divided by the sliding velocity of microtubules reflects the ATP consumption necessary per unit distance of microtubule sliding. This parameter varied according to the experimental conditions in that it increased when the ATP concentration or temperature was decreased. Our results suggest that there is not a strict stoichiometric relationship between ATP hydrolysis and sliding distance in the dynein-tubulin system, indicating that the mechanochemical coupling is different from that in beating axonemes. PMID- 4030736 TI - Thermophilic microspheres of peptide-like polymers and silicates formed at 250 degrees C. AB - We examined the possibility of chemical evolution in superheated hydrothermal environments and found the formation of microspheres at 250 degrees C and above from a mixture of glycine, alanine, valine, and aspartic acid. The microspheres did not form at lower temperatures and consisted of silicates and peptide-like polymers that contained imide bonds and amino acid residues having an abundance of valine. The results show the possibility of thermophilic cellular structures, which might be adopted by the extremely thermophilic organisms, if they exist, reported by Baross and Deming. PMID- 4030737 TI - Phosphorus-31 nuclear magnetic resonance studies on intact erythrocytes. Determination of intracellular pH and time course changes in phosphorus metabolites. AB - A method to determine the intracellular pH of intact erythrocytes using phosphorus-31 nuclear magnetic resonance spectroscopy is described. Changes in phosphorus metabolites due to the alkalization of intracellular pH were also examined. The normal erythrocytes gave signals of phosphate groups corresponding to 2,3-bisphosphoglycerate, inorganic phosphate, ATP, and NAD. Among them, the separation between alpha and gamma peaks of ATP was shown to be a good indicator of the intracellular pH free from the perturbation caused by hemoglobin. This method enabled us to determine the intracellular pH of the erythrocytes without any pretreatment. The separation between alpha and gamma peaks of ATP was also dependent on the degree of complexation with Mg2+, and was consistent with approximately 80% of total ATP complexing with Mg2+ in the samples investigated here. The pKa value of ATP in the erythrocytes was estimated to be 6.1 at 23 degrees C, which is lower than the value of 6.5 obtained for the Mg2+-free ATP solution. In the alkalized erythrocytes, fructose 1,6-bisphosphate and dihydroxyacetone phosphate were observed in addition to the metabolites found in the normal erythrocytes. Time course changes in these phosphorus metabolites were followed along with the intracellular pH monitored from ATP peaks. PMID- 4030738 TI - Intracellular proclotting enzyme in limulus (Tachypleus tridentatus) hemocytes: its purification and properties. AB - A proclotting enzyme associated with the hemolymph coagulation system of limulus (Tachypleus tridentatus) was highly purified from the hemocyte lysate. The first step of purification was performed by chromatography of the lysate on a pyrogen free dextran sulfate-Sepharose CL-6B column, which was essential for separation of the proclotting enzyme from its activator, named factor B. The following steps consisted of column chromatographies on DEAE-Sepharose CL-6B, Sephadex G-150, benzamidine-CH-Sepharose and Sephacryl S-300. Through these procedures, 1.4 mg of the purified material was obtained from 630 ml of the lysate and approximately 300-fold purification was achieved. The preparation gave a single band on sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) in the presence and absence of 2-mercaptoethanol. The single-chain proclotting enzyme was a glycoprotein with an apparent molecular weight of 54,000, and no gamma carboxyglutamic acid was detected. The proclotting enzyme was converted to its active form by purified factor B or by trypsin. The resulting clotting enzyme had a molecular weight of 54,000, consisting of a heavy chain of Mr = 31,000 and a light chain of Mr = 25,000. The serine active site of the clotting enzyme was found in the heavy chain. The chemical analyses of the isolated heavy and light chains indicated that the activation of the proclotting enzyme to its active form by factor B or trypsin is induced by a limited proteolysis, yielding two chains bridged by a disulfide linkage(s). PMID- 4030739 TI - Distinct difference in the polyamine compositions of bryophyta and pteridophyta. AB - Polyamine contents of various species of plants and fungi including Bryophyta, Pteridophyta, Gymnospermae, Ascomycota, Basidiomycota, and Lichenobionta were determined by the combination of six chromatographic techniques. Polyamines examined included putrescine, spermidine, spermine, 1,3-diaminopropane (diaminopropane), sym-norspermidine (norspermidine), sym-norspermine (norspermine), thermospermine, caldopentamine, homocaldopentamine, cadaverine, aminopropylcadaverine, sym-homospermidine (homospermidine), agmatine, and canavalmine. In addition to the widely occurring polyamines (putrescine, spermidine, and spermine), the "unusual" polyamines norspermidine and norspermine were found to be widely distributed in Bryophyta and Lichenobionta. These two polyamines were not detected in any species of Pteridophyta, Gymnospermae, and fungi even though their possible precursor, diaminopropane, was found in some species. Homospermidine was one of the major polyamines in Bryophyta and Lichenobionta, and was detected in most species of Pteridophyta and sporadically in higher plants. Agmatine was detected in most species of Bryophyta and in certain species of Gymnospermae. These data suggest that norspermidine, norspermine, and homospermidine can serve as chemical phylogenic and taxonomic markers in Plantae and Fungi. PMID- 4030740 TI - Monocyte thromboplastin (tissue factor): complementary effect of lymphocytes upon its generation by endotoxin-stimulated monkey (Macaca fuscata) cells. AB - Monkey (Macaca fuscata) mononuclear leukocytes were stimulated to produce thromboplastin (tissue factor) upon exposure to lipopolysaccharide, LPS. The stimulation was dose-related in the concentration range of 10(-5) to 10(-1) micrograms/ml of LPS. Lipid A portion of the LPS molecule was essential to induce the leukocyte ability for tissue factor generation. Thus, a lipid-lipid interaction between LPS and the cells is a plausible trigger for eliciting the ability. Approximately 50% of the tissue factor thus produced appeared to be located on the cell surface, at which the coagulation cascade is probably initiated via the activation of factor VII. Among monkey mononuclear cell populations, monocytes were responsible for LPS-induced tissue factor production. Lymphocytes amplified the basal ability of monocytes to produce the factor by two fold at physiological lymphocyte-monocyte ratios of 8:1 to 10:1. This indicates a complementary effect of lymphocytes upon the LPS-mediated monocyte ability. The medium supernatant from LPS-stimulated lymphocytes affected the monocyte competence while the stimulated lymphocytes did not. This result suggests that a soluble product of lymphocytes, i.e., lymphokine-like mediator, but not the cellular entity, participates in LPS-induced tissue factor production of monocytes. PMID- 4030741 TI - Isolation and biological activities of limulus anticoagulant (anti-LPS factor) which interacts with lipopolysaccharide (LPS). AB - Exposure of limulus hemocytes to bacterial endotoxins (lipopolysaccharide, LPS) results in the activation of the intracellular clotting system, consisting of several protein components. During the separation of these components, a potent anticoagulant, named anti-LPS factor, which inhibits the endotoxin-mediated activation of the coagulation cascade, was found in hemocytes from both Tachypleus tridentatus and Limulus polyphemus (Tanaka, S., et al. (1982) Biochem. Biophys. Res. Commun. 105, 717-723). The principle isolated from the Tachypleus hemocyte lysate by column chromatographies on dextran sulfate-Sepharose CL-6B and Sephadex G-50 under sterile conditions was a simple basic protein with an apparent molecular weight of 15,000. It consisted of a single chain polypeptide containing a total of 128 amino acids. The COOH-terminal end was presumed to be histidine, but no NH2-terminal end reactive to phenylisothiocyanate was detected. The isolated anti-LPS factor specifically inhibited the endotoxin-mediated activation of factor C, which has recently been identified as an LPS-sensitive serine protease zymogen in the hemocytes. This inhibition appeared to be due to the binding of anti-LPS factor with LPS. Moreover, anti-LPS factor had an antibacterial effect on the growth of Gram-negative bacteria (Salmonella minnesota R595 and 1114W) but not on that of Gram-positive bacteria (Staphylococcus aureus 209P). These biological activities of the isolated anti LPS factor suggest an important role in cellular defence of limulus against microbial invasion. PMID- 4030742 TI - Trypsin inhibitor in the hemolymph of a solitary ascidian, Halocynthia roretzi. Purification and characterization. AB - A purified preparation of trypsin inhibitor was obtained from the hemolymph of a solitary ascidian, Halocynthia roretzi, by a procedure including trypsin Sepharose chromatography, DEAE-cellulose chromatography, and Sephadex G-50 gel filtration. The product was a mixture of two isoinhibitors, inhibitors I and II. They were separated from each other by high-performance liquid chromatography on an anion exchanger column, and showed almost identical amino acid compositions. They were also indistinguishable in terms of apparent specific inhibitory activity against bovine trypsin when the activity was assayed with the inhibitors at rather high concentrations (greater than 50 nM). A large difference was observed between them, however, in the inhibition constants, which correspond to the dissociation constants of the inhibitor-trypsin complexes; the inhibition constant of inhibitor I was 90 pM, whereas that of inhibitor II was 4.7 nM. The molecular weights of inhibitors I and II were estimated to be 6,000 and 4,500, respectively, by SDS-polyacrylamide gel electrophoresis, while an almost identical value, 9,000, was obtained for both of them by gel filtration. The molecular weight calculated from the amino acid compositions was 5,929 for both. The isoelectric points were also identical, that is about 5.0. Both of the inhibitors were heat-stable. Ascidian inhibitor I also inhibited other trypsin like enzymes of mammalian origin, as well as those of ascidian origin. PMID- 4030743 TI - Amino acid sequences of cytochrome b5 from human, porcine, and bovine erythrocytes and comparison with liver microsomal cytochrome b5. AB - The amino acid sequences of human, porcine, and bovine erythrocyte cytochromes b5 which are soluble and present in the cytosol have been determined. In addition, the partial sequences of microsome-bound liver cytochrome b5, namely the sequence of the N-terminal region and joint region between the heme-containing and membranous part, have been established for human and porcine sources. All the cytochromes b5 from erythrocyte and liver contained N-acetylated N-termini. Of the 97 amino acid residues of erythrocyte cytochrome b5, residues 1-96 were identical with those of the liver protein of the same species. However, residue 97 (C-terminal residue) was proline for human erythrocyte cytochrome b5 and serine for the porcine protein, while residues 97 (joint region) of human and porcine liver cytochromes b5 were threonine. These findings indicate that the two forms of cytochrome b5 are encoded by two different but closely related mRNAs. PMID- 4030745 TI - Intermolecular fructosyl and levanbiosyl transfers by levan fructotransferase of Arthrobacter ureafaciens. AB - A purified levan fructotransferase preparation from the culture of the bacterium Arthrobacter ureafaciens, which produces di-D-fructose 2,6':6,2' dianhydride (difructose anhydride IV) from levan by an intramolecular levan fructosyl transfer (ILFT) reaction, was found to produce a trioligofructan and a tetraoligofructan from levan in the presence of levanbiose, indicating the intermolecular fructosyl and levanbiosyl transfer (LFT and LBT) reactions. The tri- and tetraoligofructans were identified to be levantriose and -tetraose respectively. Increase in the levanbiose concentration brought about increased production of both oligofructans with decreased formation of difructose anhydride IV, supporting the previous theory proposed by Tanaka et al. (1983) that the ILFT, LFT, and LBT reactions are catalyzed by the same enzyme. In addition, there existed a roughly stoichiometric relationship between the increase and decrease in the productions of these oligofructans, and the LBT reaction was found to occur more intensively than the LFT reaction. Acceptor specificity of the LFT and LBT reactions was studied using fifteen sugars including mono-, di-, and trisaccharides. The enzyme showed both of the reactions only with levanbiose, triose, and kestose, indicating that the exposed non-reducing levanbiosyl residue was essential for the acceptor and suggesting the existence of a levanbiosyl acceptor site on the enzyme molecule. PMID- 4030744 TI - Structure of acidic polysaccharide from cell wall of Propionibacterium acnes strain C7. AB - The structure of polysaccharide prepared by lysozyme digestion from the cell wall of Propionibacterium acnes strain C7 was examined. The polysaccharide fraction was composed of glucose, galactose, mannose, galactosamine, and diaminomannuronic acid in a molar ratio of 1:1:0.3:1:2. By Smith degradation of the polysaccharide, diaminouronic acid-containing fractions were obtained, and the configuration of diaminouronic acid was identified as 2,3-diacetamido-2,3-dideoxymannuronic acid [Man(NAc)2A] by means of 1H-NMR and 13C-NMR spectroscopic analyses. The results of analyses involving methylation and partial acid hydrolysis led to the conclusion that the polysaccharide has the repeating unit----6)Gal(alpha 1--- 4)Man(NAc)2A(beta 1----6)Glc(alpha 1----4)Man(NAc)2A (beta 1----3)GalNAc(beta 1- . In addition, a portion of the galactose residues were substituted at C-4 by alpha 1----2 linked mannotriose. PMID- 4030746 TI - Immobilization of protein ligands on new formyl-spacer-carriers for the preparation of stable and high capacity affinity adsorbents. AB - New procedures to immobilize high concentrations of protein ligands by reductive amination on two types of formyl-carriers (I & II) having different spacer lengths were investigated in order to prepare stable and high-capacity adsorbents essential for efficient affinity chromatography. Formyl-carrier (I) was prepared by reductive amination with glutaraldehyde of the amino-carrier obtained on amination of an epoxy-activated carrier. Formyl-carrier (II) was prepared by sodium metaperiodate (NaIO4) treatment of a glyceryl-carrier obtained on hydrolysis of an epoxy-activated carrier. Especially high concentrations of protein ligands were immobilized on formyl-Sepharose 4B (I) under very mild conditions (pH 7.0, 4 degrees C). A series of lectins, one of the most useful classes of group-specific ligands, was successfully immobilized by the procedures. Concanavalin A-Sepharose 4B (I) thus obtained exhibited an adsorption capacity five times greater than that of concanavalin A-Sepharose 4B made by Pharmacia Fine Chemicals, and could be repeatedly used over twenty times without a significant reduction in its adsorption capacity. PMID- 4030747 TI - Properties of porcine platelet myosin. II. Shape change of the molecule. AB - Porcine platelet myosin molecules were examined by electron microscopy for changes in their shape. At high ionic strength, the molecules were morphologically indistinguishable from skeletal muscle myosin, except for a slight difference in the bent regions of their tails. At physiological ionic strength, however, the following important difference was observed between the two myosins. Unlike skeletal muscle myosin, the filaments of nonphosphorylated platelet myosin could be disassembled by stoichiometric ATP into a monomeric form with sharply bent or folded tail, and reassembled after ATP hydrolysis. Similar disassembly changes could be induced by various nucleotide triphosphates (CTP, GTP, ITP, and UTP) and to a lesser extent by ADP, AMP, and AMPPNP. These results suggest that ATP binds to the hydrolytic sites in platelet myosin molecule and induces the molecular shape change. PMID- 4030748 TI - Involvement of C-terminal 14 residues of alkali light chain in binding to the heavy chain of myosin. AB - The alkali light chain of rabbit skeletal muscle myosin, A1, was cyanylated with 2-nitro-5-thiocyanobenzoic acid, and the peptide bond at Cys 177 was subsequently cleaved in the presence of 0.05 M CaCl2. Two peptide fragments, from the N terminal to the residue 176 (CF1) and from the residue 177 to the C-terminal (CF2), were obtained. The CD spectrum and the difference UV absorption spectrum induced by CaCl2 suggested that CF1 largely retained the higher order structure of A1. The CF1 fragment, however, could neither incorporate subfragment-1 (S-1) by an exchange reaction, nor bind with the renatured 20K fragment of S-1 heavy chain. On the other hand, the C-terminal fragment of 14 residues, CF2, could bind with the 20K fragment of S-1 heavy chain. These results indicate that the binding site of the alkali light chain for the heavy chain of myosin is located within the C-terminal 14 residues. PMID- 4030749 TI - Effect of dinitrophenyl modification on oxidation-reduction of glutathione reductase from yeast. AB - Covalent modification of glutathione reductase (GR) from yeast with 1-fluoro-2,4 dinitrobenzene (FDNB) inhibited the NADPH-GSSG reductase activity completely. This modification also decreased the NADPH-thio-NADP+ transhydrogenase activity, stimulated the NADPH-oxidase activity, and induced the NADPH-cytochrome c reductase activity. Spectrophotometric titration showed that one tyrosine residue per FAD was modified with a dinitrophenyl group. The modified enzyme showed conversion of the two-electron reduced form (EH2) to the four-electron reduced form (EH4) in anaerobic conditions and conversion of EH2 to the oxidized form (E) in aerobic conditions. These results indicate that the modification of one tyrosine residue of the active site induces the instability of EH2. PMID- 4030750 TI - Application of a fluorogenic reagent, ammonium 7-fluorobenzo-2-oxa-1,3-diazole-4 sulfonate for detection of cystine-containing peptides. AB - A simple, sensitive and reliable method for the detection of cystine-containing peptides has been developed. A peptide bridged with a disulfide bond was reduced and cleaved with tributylphosphine, and then coupled with a thiol specific reagent, ammonium 7-fluorobenzo-2-oxa-1,3-diazole-4-sulfonate, under alkaline conditions. After incubation at 60 degrees C for 1 h, the fluorescent derivative formed was measured with excitation at 385 nm and emission at 515 nm. The intensity of fluorescence labeled to the peptide was very stable and the peptide containing disulfide was quantitatively determined in the range of 100 pmol to 10 nmol, when oxidized glutathione was used as a standard. This method was very useful for specific detection of cystine-containing peptides in the column effluents on reverse phase high performance liquid chromatography. PMID- 4030751 TI - Crystallization of calcium-calmodulin-trifluoperazine complex and an attempt at crystallizing calcium-free calmodulin. AB - Crystals suitable for X-ray structure analysis were obtained for CaM complexed with both calcium ions and a phenothiazine drug, trifluoperazine (TFP). The TFP/CaM binding ratio in crystals was experimentally determined to be nearly 1. An attempt at crystallizing calcium-free calmodulin (CaM) resulted in rigid but non-birefringent solids which exhibited no X-ray reflections. PMID- 4030752 TI - Establishing a microcomputer lab in a medical university library. PMID- 4030753 TI - Electron microscopy as a tool for scientific illustrators. AB - Medical and biological illustrators can be aided in drawing small specimens by micrographs from the scanning (SEM) or transmission (TEM) electron microscope. These detailed photographs act as a reference because they show surface detail in exquisite resolution. To help the illustrator understand this tool, a functional explanation of the electron microscope is provided and techniques for application are presented. PMID- 4030754 TI - Complexities in the denaturation of horse metmyoglobin by guanidine hydrochloride. AB - The denaturation of horse metmyoglobin by guanidine hydrochloride was studied at pH 6.4 and 25 degrees C. Measurements of both the peptide circular dichroism and the absorbance in the Soret region suggest that the extent of renaturation strongly depends on the time interval during which the protein is exposed to concentrated solutions of the denaturant. From the equilibrium measurements of the absorption in the Soret region, it is concluded that the unfolding of metmyoglobin is complex. This is further supported by kinetic studies of denaturation which suggest the occurrence of the least four species in the reaction. PMID- 4030755 TI - Separation, purification, partial characterization and comparison of the heavy and light chains of botulinum neurotoxin types A, B, and E. AB - Clostridium botulinum produces botulinum neurotoxin (NT) in antigenically distinct forms. When isolated from bacterial cultures type E is a single chain, type B is a mixture of single and two-chain molecules, and type A is essentially a two-chain molecule (Mr approximately 150,000). Protease(s) in the cultures or trypsin nick single-chain NT to the two-chain form. The heavy (Mr approximately 100,000) and light (Mr approximately 50,000) chains of the two-chain molecule remain held together by -S-S-bond(s). The two chains are presumed to have different functions. NT binds to nerve cells via the heavy chain and then light chain enters the cell and blocks release of acetylcholine (Simpson, L. L. (1981) Pharmacol. Rev. 33, 155-188). We nicked single-chain NT to form the two-chain form with trypsin, minimizing secondary cleavages, then separated and purified the heavy and light chains using ion-exchange chromatography. The technique, with minor modifications, is a generalized method for types A, B, and E. These subunit chains (each a single band in sodium dodecyl sulfatepolyacrylamide gel electrophoresis) were analyzed for their complete amino acid compositions. The amino acid contents of the heavy and light chains agreed well with the parent two chain molecule. This affirms that NT is composed of two chains. The two subunit chains are now usable for amino acid sequence and other studies. Comparison of the amino acid contents indicates more similarity among the light chains than the heavy chains of the three NT types, a similarity that agrees with our published partial amino acid sequences (first 13-18 residues) of these chains. Several (up to 9) different amino acid residues of the heavy chain (which is twice the size of the light chain) are present in double the number of corresponding residues in the light chain. PMID- 4030756 TI - N tau-Ribosylhistidine, a novel histidine derivative in urine of histidinemic patients. Isolation, structure, and tissue level. AB - On amino acid analysis of urine of histidinemic patients, an unidentified compound was eluted in a position between beta-aminoisobutyric acid and gamma aminobutyric acid. This compound was purified to homogeneity from the urine by a combination of extraction with 80% ethanol, repeated column chromatography on Bio Rad AG-50, and high performance liquid chromatography on a strongly cationic ion exchanger. The compound yielded free histidine on hydrolysis in an evacuated sealed tube with 0.1-6.0 M HCl at 145 degrees C for 5 h, but not at 100 degrees C for 24 h. This compound was determined to be N tau-ribosylhistidine by 1H and 13C NMR spectroscopies. The urinary content of this material in normal and histidinemic children was 17.8 +/- 13.4 (n = 10) and 126 +/- 51 (n = 14) mumol/g creatinine (mean +/- S.D.), respectively, and were closely correlated with those of urinary histidine. The renal clearance value of N tau-ribosylhistidine in humans was 96% of that of creatinine. When rats were fed on diets rich in histidine, the urinary excretion of N tau-ribosylhistidine increased greatly and was well correlated with the intake of histidine. PMID- 4030757 TI - Peroxidase-catalyzed O-demethylation reactions. Quinone-imine formation from 9 methoxyellipticine derivatives. AB - Despite numerous reports on the N-demethylation reactions catalyzed by peroxidases, to our knowledge, O-demethylation reactions with the same enzymes seem to be still a questionable matter. Unexpectedly, a peroxidase system (horseradish peroxidase and hydrogen peroxide) is able to effect the O demethylation of the cytotoxic agents 9-methoxyellipticine and N2-methyl-9 methoxyellipticinium acetate. The reaction leads directly to the formation of the corresponding quinone-imine derivatives with the concomitant formation of one molecule of methanol per molecule of methoxy compound. One hydrogen peroxide molecule is consumed during the process. Experiments in H218O-enriched water clearly indicate that 18O is nearly quantitatively incorporated in the carbonyl group of the generated quinone-imine compound with the concomitant elimination of the methoxy group as methanol. So this peroxidase-catalyzed apparent O demethylation in fact implies an oxidative demethoxylation step. This enzymatic reaction exhibits normal Michaelis-Menten saturation kinetics. Like the 9 hydroxylated ellipticines, both the 9-methoxylated ellipticines show a good affinity for the peroxidase itself (Km approximately 10 microM) but are slowly transformed to the corresponding quinone-imines. The Vmax values for methoxylated ellipticines are 10(-1)-10(-3) lower than those for hydroxylated compounds. This new route for the in vitro formation of electrophilic derivatives from the cytotoxic 9-methoxyellipticine and N2-methyl-9-methoxyellipticinium might be considered as a novel possible metabolic pathway for these drugs, especially if we bear in mind the "bio-oxidative alkylation" process previously described for at least one of the corresponding hydroxylated ellipticine derivatives (see Bernadou, J., Meunier, B., Meunier, G., Auclair, C., and Paoletti, C. (1984) Proc. Natl. Acad. Sci. U.S.A. 81, 1297-1301; and Monsarrat, B., Maftouh, M., Meunier, G., Dugue, B., Bernadou, J., Armand, J. P., Picard-Fraire, C., Meunier, B., and Paoletti, C. (1983) Biochem. Pharmacol. 32, 3887-3890). PMID- 4030758 TI - Chemical modification of pig kidney 3,4-dihydroxyphenylalanine decarboxylase with diethyl pyrocarbonate. Evidence for an essential histidyl residue. AB - Diethyl pyrocarbonate inhibits pig kidney holo-3,4-dihydroxyphenylalanine decarboxylase with a second-order rate constant of 1170 M-1 min-1 at pH 6.8 and 25 degrees C, showing a concomitant increase in absorbance at 242 nm due to formation of carbethoxyhistidyl derivatives. Activity can be restored by hydroxylamine, and the pH curve of inactivation indicates the involvement of a residue with a pKa of 6.03. Complete inactivation of 3,4-dihydroxyphenylalanine decarboxylase requires the modification of 6 histidine residues/mol of enzyme. Statistical analysis of the residual enzyme activity and of the extent of modification shows that, among 6 modifiable residues, only one is critical for activity. Protection exerted by substrate analogues, which bind to the active site of the enzyme, suggests that the modification occurs at or near the active site. The modified inactivated 3,4-dihydroxyphenylalanine decarboxylase still retains most of its ability to bind substrates. Thus, it may be suggested that the inactivation of enzyme by diethyl pyrocarbonate is not due to nonspecific steric or conformational changes which prevent substrate binding. However, the modified enzyme fails to produce at high pH either an enzyme-substrate complex or an enzyme-product complex absorbing at 390 nm. Considerations on this peculiar feature of the modified enzyme consistent with a catalytic role for the modified histidyl residue are discussed. The overall conclusion of this study may be that the modification of only one histidyl residue of 3,4-dihydroxyphenylalanine decarboxylase inactivates the enzyme and that this residue plays an essential role in the mechanism of action of the enzyme. PMID- 4030759 TI - Metabolism of all-trans-retinoic acid and all-trans-retinyl acetate. Demonstration of common physiological metabolites in rat small intestinal mucosa and circulation. AB - The kinetics and metabolism of physiological doses of all-trans-retinoic acid were examined in blood and small intestinal mucosa of vitamin A-depleted rats. A major portion of intrajugularly injected retinoic acid is rapidly (within 2 min) sequestered by tissues; subsequently 13-cis-retinoic acid and polar metabolites are released into circulation. All-trans-retinoic acid appears in small intestinal epithelium within 2 min after dosing and is the major radioactive compound there for at least 2 h. Retinoyl glucuronide and 13-cis-retinoic acid are early metabolites of all-trans-retinoic acid in the small intestine of bile duct-cannulated rats. Retinoyl glucuronide, the major metabolite of retinoic acid intestinal epithelium, in contrast to other polar metabolites, was not detected in circulation. An examination of [3H]retinyl acetate metabolites under steady state conditions in vitamin A-repleted rats demonstrates the occurrence of all trans-retinoic acid and 13-cis-retinoic acid in circulation and in intestinal epithelium, in a pattern similar to that found after injection of retinoic acid into vitamin A-depleted rats. Our data establish that all-trans-retinoic acid, 13 cis-retinoic acid, and retinoyl glucuronide are physiological metabolites of vitamin A in target tissues, and therefore are important candidates as mediators of the biological effect of the vitamin. PMID- 4030760 TI - Nonhistone chromosomal protein HMG 1 interactions with DNA. Fluorescence and thermal denaturation studies. AB - The interaction of high mobility group protein 1 (HMG 1) isolated from chicken erythrocytes with DNA has been characterized using the intrinsic tryptophan fluorescence of the protein as a probe. It was found that the fluorescence is quenched approximately 30% upon binding to either single- or double-stranded DNA. Fluorescent titrations indicate that the physical site size for HMG 1 binding on native DNA is approximately 14 base pairs (or 14 bases for binding to single stranded DNA). Binding to single-stranded poly(dA) is only slightly dependent on ionic strength, although the affinity for double-stranded DNA is strongly ionic strength-dependent and has an optimum at approximately 100-120 mM Na+. Above this range, binding to native DNA is virtually all electrostatic in nature. Although the affinity of HMG 1 for single-stranded DNA is higher than that for double stranded DNA at the extremes of the ionic range studied, no clear evidence for a helix-destabilizing activity was obtained. At low ionic strength, the protein actually stabilized DNA against thermal denaturation, while at high ionic strength, HMG 1 appears to undergo denaturation below the Tm of the DNA. Studies of the environment of the tryptophan fluorophores using collisional quenchers iodide, cesium, and acrylamide suggest that the predominant fluorophore is relatively exposed but constrained in a rigid, positively charged environment. PMID- 4030762 TI - Interaction of cytochrome P-450 with a hydroperoxide derived from butylated hydroxytoluene. Mechanism of isomerization. AB - Attack of O2 on the phenoxy radical derived from butylated hydroxytoluene resulted in the formation of 2,6-di-t-butyl-4-hydroperoxy-4-methyl-2,5 cyclohexadienone (BOOH). This hydroperoxide was rapidly consumed when incubated with rat liver microsomes in the absence of NADPH. The destruction of BOOH was accompanied by formation of the corresponding alcohol (BOH) and a derivative of the alcohol (B(OH)2) in which a t-butyl methyl group was hydroxylated. This diol was produced also when BOH was incubated with microsomes and NADPH, but at a slower rate. Mass spectral analyses of B(OH)2 formed from substrates labeled with either 2H or 18O, showed that oxygen was transferred from the peroxy group to a t butyl group (via the heme iron of P-450) without migration of the intermediate alcohol from the enzyme active site. The results support a mechanism involving heterolytic O-O bond cleavage during isomerization of the hydroperoxide to B(OH)2. The chiral diol was produced from BOOH nonstereoselectively, but the NADPH/O2-supported hydroxylation of BOH resulted in the formation of a 20% excess of one enantiomer of B(OH)2. Analyses of products formed from the interaction of cumene hydroperoxide with cytochrome P-450 showed that this substrate undergoes rearrangement also; 2-phenyl-1,2-propanediol was produced, together with cumyl alcohol and acetophenone. These results indicate that isomerization competes with other pathways of hydroperoxide destruction by cytochrome P-450. PMID- 4030761 TI - Glycation of amino groups in protein. Studies on the specificity of modification of RNase by glucose. AB - Ribonuclease A has been used as a model protein for studying the specificity of glycation of amino groups in protein under physiological conditions (phosphate buffer, pH 7.4, 37 degrees C). Incubation of RNase with glucose led to an enhanced rate of inactivation of the enzyme relative to the rate of modification of lysine residues, suggesting preferential modification of active site lysine residues. Sites of glycation of RNase were identified by amino acid analysis of tryptic peptides isolated by reverse-phase high pressure liquid chromatography and phenylboronate affinity chromatography. Schiff base adducts were trapped with Na-BH3CN and the alpha-amino group of Lys-1 was identified as the primary site (80-90%) of initial Schiff base formation on RNase. In contrast, Lys-41 and Lys-7 in the active site accounted for about 38 and 29%, respectively, of ketoamine adducts formed via the Amadori rearrangement. Other sites reactive in ketoamine formation included N alpha-Lys-1 (15%), N epsilon-Lys-1 (9%), and Lys-37 (9%) which are adjacent to acidic amino acids. The remaining six lysine residues in RNase, which are located on the surface of the protein, were relatively inactive in forming either the Schiff base or Amadori adduct. Both the equilibrium Schiff base concentration and the rate of the Amadori rearrangement at each site were found to be important in determining the specificity of glycation of RNase. PMID- 4030763 TI - Intracellular Ca2+ mobilization activated by extracellular ATP in Ehrlich ascites tumor cells. AB - Addition of 0.4-25 microM extracellular ATP results in transient, dose-dependent increases in cytosolic free calcium measured in Ehrlich ascites tumor cells. In cells incubated with 1 mM extracellular Ca2+, ATP induces a triphasic Ca2+ transient: an initial rapid increase (2-3 s), a second, slower phase of increase (60-90 s), and, finally, a gradual return to near resting [Ca2+]i (4-5 min). Several findings demonstrate that the initial, rapid phase of Ca2+ transient results from a mobilization of Ca2+ from a non-mitochondrial intracellular store, while the second, slow phase of increase is produced by enhanced influx of Ca2+ across the plasma membrane. Successive additions of extracellular ATP can elicit repetitive Ca2+ transients if the initially added ATP is removed either through the action of native ecto-ATPase activity or exogenous hexokinase. Other adenine nucleotides, including non-hydrolyzable ATP analogs, neither alter cytosolic [Ca2+] nor antagonize the ATP-induced effects. Conversely, other nucleotide triphosphates (ITP, UTP, and GTP) induce Ca2+ transients which are identical to those produced by ATP. A variety of experimental results indicate that these actions of ATP and other nucleotide triphosphates are not due to a generalized increase in plasma membrane permeability. The results suggest that, in these transformed cells, ATP may act in a manner similar to other Ca2+ mobilizing hormones and growth factors. PMID- 4030764 TI - Purification, calcium-binding properties, and conformational studies on a 28-kDa cholecalcin-like protein from bovine brain. AB - A large-scale preparation method for bovine brain 28-kDa cholecalcin-like protein is described. Flow dialysis binding studies revealed that the protein binds at least 3 mol of Ca2+/mol of protein. The protein undergoes conformational changes on binding calcium as shown by UV differential absorption spectroscopy, near and far UV circular dichroism, and intrinsic fluorescence. Circular dichroism (CD) studies in the far UV indicate an apparent increase in helical content in the presence of Ca2+. The effect of calcium on the protein structure is nearly maximum for 1 Ca2+ bound/protein molecule. UV differential absorption studies on the binding of the Ca2+ agonist Tb3+ and Tb3+ luminescence induced by energy Trp- --Tb3+ transfer indicate that Tb3+ binds to two higher affinity Ca2+-binding sites. These sites are probably very close to the single Trp residue. Analysis of the fluorescence parameters of the single tryptophan residue in the apoprotein and its accessibility to ionic and neutral quenchers suggests that this residue is located in a highly hydrophobic domain on the protein surface. PMID- 4030766 TI - The subunit structure and active site sequence of porcine spleen deoxyribonuclease. AB - An acid DNase (DNase II) from porcine spleen was purified by sequential chromatography over carboxymethyl-cellulose, blue dextran-Sepharose, hydroxylapatite, and sulfoxyethyl-cellulose. The purified enzyme shows two polypeptide bands on sodium dodecyl sulfate-polyacrylamide gel electrophoresis at Mr 35,000 (alpha chain) and 10,000 (beta chain). The sum of the two molecular weights is that of the native enzyme (45,000). Thus, the DNase II molecule is an alpha,beta dimer. The two polypeptides are not joined by disulfide bonds, but can be cross-linked chemically with dimethyl suberimidate. They are dissociable in 8 M urea, after which they can be isolated by gel filtration on Sephadex G-100, eluting with 1 M acetic acid. Once dissociated, the two polypeptides cannot be reassociated to regenerate DNase II activity. The sum of the amino acid compositions of the two polypeptides is that of the native enzyme, and both contain carbohydrate. The beta chain is devoid of histidine, half-cystine, valine, and methionine. The NH2-terminal amino acid of the alpha chain is leucine, while that of the beta chain cannot be identified by either dansylation or Edman degradation. Alkylation of an essential histidine residue of DNase II occurs on incubation of the enzyme with [2-14C] ICH2COOH (Oshima, R. G., and Price, P. A. (1973) J. Biol. Chem. 248, 7522-7526). Radioactivity is found only in the alpha chain. After hydrolysis of the alpha chain with trypsin, chymotrypsin, and thermolysin, radioactive peptides were isolated by gel filtration on Sephadex G-25 and reversed-phase high performance liquid chromatography. Sequence analyses of the radioactive peptides show alkylation of 1 of 9 histidines in the entire amino acid sequence of DNase II. The sequence around this histidine, determined by manual microsequencing and by the release of amino acids with carboxypeptidases A and B, is Ala-Thr-Glu-Asp-His-Ser-Lys-Trp. PMID- 4030765 TI - Amino acid sequence of a proline-rich phosphoglycoprotein from parotid secretion of the subhuman primate Macaca fascicularis. AB - The complete amino acid sequence of the macaque proline-rich phosphoglycoprotein (MPRP) was determined by automated Edman degradation of the protein, fragments F 1 and F-2 derived from the protein by an intrinsic salivary protease, and chymotryptic, tryptic, Staphylococcus aureus V8 protease, and endoproteinase lysine-C peptides. MPRP contains 115 amino acid residues including phosphorylated serine at residues 1, 2, 6, 12, and 15, and 6 O-glycosidic carbohydrate units at residues 69, 75, 87 (threonine) and 96, 103, and 106 (serine). The Mr of the polypeptide moiety of the protein is 12,656. The amino-terminal domain contains all 5 phosphoserine residues and most of the other negatively charged and hydrophilic residues, whereas the carboxyl-terminal domain contains 24 of 25 proline residues, and 6 O-glycosidic oligosaccharides. Comparison of MPRP with the four major anionic proline-rich proteins (PRPs) from human glandular secretion shows that 57% of the amino acid residues are identical if gaps are introduced to maximize homology, suggesting that these proteins are phylogenetically related. Significant structural and functional differences occur between the macaque and human proteins. MPRP has 5 phosphoserines, PRPs have 2. MPRP is a glycoprotein, PRPs are not. MPRP inhibits the spontaneous precipitation (primary precipitation) of calcium phosphate salts from supersaturated solutions in addition to inhibiting seeded crystal growth (secondary precipitation) (Oppenheim, F. G., Offner, G. D., and Troxler, R. F. (1982) J. Biol. Chem. 257, 9271-9282), whereas PRPs inhibit only secondary precipitation. MPRP is the only major anionic proline-rich protein in macaque glandular secretion; in contrast, there are four major anionic PRPs and these display a genetic polymorphism. The significance of these structural differences with respect to biological function and the possible relationship of MPRP to salivary mucins are discussed. PMID- 4030767 TI - Purification and characterization of human lipoprotein lipase and hepatic triglyceride lipase. Reactivity with monoclonal antibodies to hepatic triglyceride lipase. AB - Human lipoprotein lipase and hepatic triglyceride lipase were purified to homogeneity from post-heparin plasma. These enzymes were purified 250,000- and 100,000-fold with yields of 27 +/- 15 and 19 +/- 6%, respectively. Molecular weight determination by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate and reducing agents yielded Mr of 60,500 +/- 1,800 and 65,200 +/- 400, respectively, for lipoprotein lipase and hepatic triglyceride lipase. These lipase preparations were shown to be free of detectable antithrombin by measuring its activity and by probing of Western blots of lipases with a monospecific antibody against antithrombin. In additions, probing of Western blots with concanavalin A revealed no glycoproteins corresponding to the molecular weight of antithrombin. Four stable hybridoma-producing distinct monoclonal antibodies (mAb) to hepatic triglyceride lipase were isolated. The specificity of one mAb, HL3-5, was established by its ability to immunoprecipitate hepatic triglyceride lipase catalytic activity. Interaction of HL3-5 with this lipase did not inhibit catalytic activity. The three other mAb interacted with hepatic triglyceride lipase only after denaturation of the enzyme with detergents. The relatedness of these two enzymes was examined by comparing under the same conditions the thermal inactivation, the sensitivity to sulfhydryl and reducing agents, amino acid composition, and the mobility of peptide fragments generated by cyanogen bromide cleavage. The results of these studies strongly support the view that the two enzymes are different proteins. Immunological studies confirm this conclusion. Four mAb to hepatic triglyceride lipase did not interact with lipoprotein lipase in Western blots, enzyme-linked immunosorbent assay, and immunoprecipitation experiments. These immunological studies demonstrate that several epitopes of the hepatic triglyceride lipase protein moiety are not present in the lipoprotein lipase molecule. PMID- 4030768 TI - The biosynthesis and fatty acid acylation of the murine erythrocyte sialoglycoproteins. AB - The biosynthesis and post-translocational processing of the murine erythrocyte sialoglycoproteins gp2 and gp3 have been studied on splenic erythroblasts obtained from mice rendered anemic by treatment with phenylhydrazine. A putative precursor-product relationship has been established between gp3 and a peptide (gp3pr) of apparent Mr = 22,000. No precursor to gp2 has been found. gp3pr was selectively and efficiently converted to gp3 in pulse-chase experiments after a 45-60-min chase. [3H]Palmitate labeled a series of splenic cell proteins, including gp2, gp3, and gp3pr. Chemical analyses indicated that the fatty acid is covalently linked to protein by an ester bond. Splenic cells incorporated [3H]galactose in both gp2 and gp3 but not in gp3pr. The results indicate that the murine sialoglycoproteins are modified in succession by fatty acid acylation and terminal glycosylation. [3H]Palmitate labeling appears to be an early modification that affects concomitantly gp3pr and gp3, suggesting that fatty acid acylation is a cytosolic event not obligatorily coupled to translocation. PMID- 4030769 TI - Interaction of proteoglycans with the pericellular (1 alpha, 2 alpha, 3 alpha) collagens of cartilage. AB - Interaction between cartilage proteoglycan and the collagen(s) composed of 1 alpha, 2 alpha, and 3 alpha chains was studied in vitro. Most of the collagen was insoluble under the conditions of assay (0.15 M NaCl, 0.008 M phosphate buffer, pH 7.4; 4 degrees C) and was in the form of fibrils 20 nm in diameter or thinner. The larger fibrils had 60-70 nm periodicity, characteristic of native collagens. Proteoglycan monomers which had been labeled by incubating cartilage slices in vitro with Na2 35SO4 were used to assay the interaction. The insoluble collagen fraction bound proteoglycan from solution. At proteoglycan:collagen ratios lower than 1:2, binding was rapid and linear, and the dissociation constant was 1.7 X 10(-9) M. At higher proteoglycan:collagen ratios, more proteoglycan was bound, but at a slower rate. Binding of proteoglycan to collagen did not require fibrils, since soluble 1 alpha, 2 alpha, and 3 alpha containing collagen also bound to proteoglycan and formed an insoluble complex. Denatured collagens did not bind proteoglycan or compete for binding with normal collagen. Optimum binding occurred with intact proteoglycan, but proteoglycan which had been treated with protease was also bound at low levels. Both protease-treated proteoglycan and free chondroitin sulfate competed with intact proteoglycan in the binding assays, but neither chondroitinase ABC-treated proteoglycan nor the oligosaccharides produced by digestion of chondroitin sulfate with testicular hyaluronidase altered the binding of proteoglycan to collagen. Hyaluronic acid did not compete with radioactive proteoglycan, but heparin and dextran sulfate were extremely effective inhibitors of binding. These data suggest a relatively nonspecific interaction between sulfated polyanions and 1 alpha, 2 alpha, and 3 alpha containing collagens. However, given the location of these collagens near the chondrocyte surface, the interaction of fibrillar 1 alpha, 2 alpha, 3 alpha collagen with proteoglycan is likely to occur and to be of biological importance. PMID- 4030770 TI - Single and twinned crystals of ribulose-1,5-bisphosphate carboxylase-oxygenase from Alcaligenes eutrophus. AB - Ribulose-1,5-bisphosphate carboxylase-oxygenase (L8S8) from Alcaligenes eutrophus has been crystallized by equilibrium vapor diffusion techniques with ammonium sulfate as precipitant. Crystals thus obtained either as the ternary complex with CO2 and Mg2+ or as the quaternary complex with CO2, Mg2+, and 2-carboxyarabinitol 1,5-bisphosphate, a transition state analogue, diffract at least to 2.8-A resolution. Both are essentially isomorphous to each other, having orthorhombic space group C222(1) with cell dimensions a = 159 A, b = 159 A, and c = 200 A, and there is half a molecule in the asymmetric unit. The crystals of the ternary complex are sometimes twinned about the c axis so that the space group appears to be tetragonal. In this light, our earlier report (Bowien, B., Mayer, F., Spiess, E., Pahler, A., Englisch, U., and Saenger, W. (1982) Eur. J. Biochem. 106, 405 410) on a tetragonal space group P4(2)2(1)2 with crystals obtained from the same enzyme with Mg2+ and CO2 but without 2-carboxyarabinitol 1,5-bisphosphate might be incorrect. PMID- 4030771 TI - Calmodulin inhibits interaction of actin with MAP2 and Tau, two major microtubule associated proteins. AB - We have previously shown that microtubule-associated protein 2 (MAP2) and Tau, two major microtubule-associated proteins, interact with actin differently as measured by low-shear viscosity and that their activities are modified by phosphorylation (Nishida, E., Kotani, S., Kuwaki, T., and Sakai, H. (1982 in Biological Functions of Microtubules and Related Structures (Sakai, H., Mohri, H., and Borisy, G. G., eds) pp. 297-309, Academic Press, Japan). In the present study we further examined their interaction using turbidimetry, electron microscopy, low- and high-shear viscometry. MAP2 increased the low-shear viscosity of actin filament but had weaker effect on high-shear viscosity and turbidity of actin filaments. In contrast, Tau reduced high-shear viscosity of actin filaments and enhanced the turbidity which were due to formation of actin filament bundles as shown by electron microscopy. We conclude that MAP2 is a gelation factor, while Tau is a bundling factor. A well-known Ca2+-dependent regulatory protein, calmodulin, inhibited both MAP2-actin and Tau-actin interaction in a Ca2+-dependent manner. The calmodulin-dependent inhibition was canceled by higher concentrations of MAP2 or Tau, and calmodulin had no effect on the viscosity of actin filament alone, indicating that this inhibition is based on the stoichiometric interaction of calmodulin with MAP2 or Tau. PMID- 4030772 TI - Organization of Krebs tricarboxylic acid cycle enzymes in mitochondria. AB - Sonic oscillation of mitochondria usually leads to the release of a number of Krebs tricarboxylic acid cycle enzymes. These enzymes have, therefore, been referred to as soluble matrix enzymes. In the present report, we show that gentle sonic or osmotic disruption can be used to obtain a mitochondrial preparation where these enzymes appear to be organized in a large complex of proteins. Using citrate synthase as a marker for these enzymes, we show that the proposed complex is easily sedimented at 32,000 X g in 30 min. The exposed citrate synthase in these complexes can be inhibited by its antibody, indicating that the enzymes are not merely entrapped in substrate-permeable vesicles. The effects of pH, temperature, ionic strength, and several metabolites on the ability to obtain the sedimentable citrate synthase have been tested. These studies indicate that the complex is stable at conditions presumed to exist in situ. Electron microscopic studies show that gentle sonic oscillation gives rise to an efflux of mitochondrial matrix contents which tend to remain attached to the original membranes. The sedimentable fraction also contained four other presumably soluble Krebs tricarboxylic acid cycle enzymes: aconitase, NAD+-isocitrate dehydrogenase, fumarase, and malate dehydrogenase. PMID- 4030773 TI - Disulfide spacer between methotrexate and poly(D-lysine). A probe for exploring the reductive process in endocytosis. AB - Poly(D-lysine) is taken up avidly by cultured cells through adsorptive endocytosis and can serve as a carrier to increase cellular uptake of other molecules. While direct conjugation of methotrexate to poly(D-lysine) yields a conjugate devoid of cytotoxic effects because poly(D-lysine) is not digested in lysosomes, the indirect conjugation using a triglycine spacer or a disulfide spacer strongly inhibits the growth of both the wild type and the methotrexate transport-defective Chinese hamster ovary cells. Cell treatment with 3 mM NH4Cl or 50 micrograms/ml leupeptin prevents the effect of conjugate with the triglycine spacer, but not of conjugate with the disulfide spacer. On the other hand, preincubation with 2-mercaptoethanol abolishes the effect of the drug disulfide conjugate in the methotrexate transport-defective mutant, but not the effect of the drug-triglycine conjugate. The disulfide conjugate shows an identical cytotoxic effect in alpha-minimal essential medium and RPMI 1640 media, even though cells grown in the latter have only half the glutathione content as cells grown in the former medium. We conclude that the reductive process through which methotrexate is released from the disulfide spacer (a) occurs inside cells and not at the cell surface, (b) requires neither acid pH nor lysosomal enzymes, and (c) is not mediated by a glutathione-disulfide exchange reaction requiring high glutathione concentrations. Although the cellular compartment in which this reductive process occurs is not yet identified, there are reasons to assume that it is prelysosomal. PMID- 4030774 TI - Protein carboxyl methyltransferase selectively modifies an atypical form of calmodulin. Evidence for methylation at deamidated asparagine residues. AB - Prolonged incubation of native bovine brain calmodulin with S-adenosyl-L-[methyl 3H]methionine and protein carboxyl methyltransferase results in maximal methylation of only 1-2% of the calmodulin molecules. In contrast, calmodulin which has been subjected to a prior alkaline treatment (0.1 M NH4OH, 37 degrees C for 3 h) can be methylated to a level of 30-50%. This treatment is known to be effective in deamidating certain asparagine residues which lie in unstable sequences, particularly -Asn-Gly- sequences. Bovine brain calmodulin has three such sequences (Watterson, D. M., Sharief, F., and Vanaman, T. C. (1980) J. Biol. Chem. 255, 962-975). The enhancement of methylation by alkaline treatment is substantially reduced if calmodulin is first reacted with bis-(I,I trifluoroacetoxy)iodobenzene, a reagent which converts the carboxamide group of asparagine and glutamine residues to the corresponding primary amines. Thus, protein carboxyl methyltransferase selectively modifies an abnormal form of calmodulin that is probably deamidated. These findings suggest that protein carboxyl methylation may play a role in the disposition of abnormal proteins which contain atypical, isomerized aspartyl residues arising via spontaneous deamidation of unstable asparagines. PMID- 4030775 TI - Thermodynamics of the Ca2+ binding to bovine alpha-lactalbumin. AB - Bovine alpha-lactalbumin contains one strong Ca2+-binding site. The free energy (delta G0), enthalpy (delta H0), and entropy (delta S0) of binding of Ca2+ to this site have been calculated from microcalorimetric experiments. The enthalpy of binding was dependent on the metal-free bovine alpha-lactalbumin concentration. At 0.8 mg ml-1, metal-free bovine alpha-lactalbumin delta H0 was 110 +/- 6 kJ mol-1. At this concentration the binding constant was estimated from a mathematical analysis of the titration curves to be greater than 10(7) M-1. This means that delta G0 is smaller than -40 kJ mol-1 and delta S0 is less negative than -235 J.K-1 mol-1. The binding of Ca2+ is therefore enthalpy-driven. From binding experiments as a function of temperature, a delta Cp value of -4.1 kJ.K-1 mol-1 was calculated. This value is dependent on the protein concentration. A tentative explanation for this large value is given. PMID- 4030776 TI - Biosynthesis of platelet activating factor. Substrate specificity of 1-alkyl-2 lyso-sn-glycero-3-phosphocholine:acetyl-CoA acetyltransferase in rat spleen microsomes. AB - The substrate requirements and specificity of 1-alkyl-2-lyso-sn-glycero-3 phosphocholine (alkyllyso-GPC):acetyl-CoA acetyltransferase were investigated. The following findings were observed. 1) When the ether bond of alkyllyso-GPC is substituted with an ester linkage, the resulting compound, palmitoyllyso-GPC, can serve as a substrate, albeit at a reduced rate (50%). In addition, palmitoyllyso GPC is a competitive inhibitor in the reaction with respect to concentration dependence of alkyllyso-GPC and a noncompetitive inhibitor when the concentrations of acetyl-CoA are varied. 2) Octadecyllyso-GPC is acetylated at a slightly higher rate than hexadecyllyso-GPC and unsaturated alkyllyso-GPC is a preferable substrate to its saturated counterpart. 3) The homologous series of short chain acyl-CoAs demonstrate an inverse relationship of chain length with the values of their apparent Km and Vmax, e.g. the longer the acyl-CoA chain, the smaller the values of Vmax and apparent Km. 4) The effect of polar head group modification of alkyllyso-GPC on the acetyltransferase activity is related to the degree of methylation of the amine group. The choline base analog gives the highest enzyme activity and the ethanolamine derivative is the least active, while N', N'-dimethylethanolamine and monomethylethanolamine analogs are the substrates with intermediate activities. These results on substrate selectivity of acetyltransferase correlate with the known structural requirements essential for the biological activities elicited by platelet activating factor and thus suggest that the acetyltransferase activating factor and thus suggest that the acetyltransferase may be important in governing the chemical structure of platelet activating factor synthesized in vivo. PMID- 4030777 TI - Reserpic acid as an inhibitor of norepinephrine transport into chromaffin vesicle ghosts. AB - Reserpic acid, a derivative of the antihypertensive drug reserpine, inhibits catecholamine transport into adrenal medullary chromaffin vesicles. Since it does not affect the membrane potential generated by the H+-translocating adenosine triphosphatase but inhibits ATP-dependent norepinephrine uptake with a Ki of about 10 microM, reserpic acid must block the H+/monoamine translocator. Because reserpic acid is much more polar than reserpine, it does not permeate the chromaffin vesicle membrane, nor is it transported into chromaffin vesicle ghosts in the presence of Mg2+-ATP. Although it inhibits norepinephrine transport when added externally, reserpic acid does not inhibit when trapped inside chromaffin vesicle ghosts. Therefore, reserpic acid must bind to the external face of the monoamine translocator and should be a good probe of the translocator's structural asymmetry. PMID- 4030778 TI - Isolation and sequence of a tryptic peptide containing the autophosphorylation site of the regulatory subunit of bovine brain protein kinase II. AB - The regulatory subunit (RII-B) of bovine brain protein kinase II and the well characterized regulatory subunit of heart protein kinase II (RII-H) exhibit similar physicochemical properties, but differ significantly in their peptide maps and antigenic determinants. As a starting point for studying structure/function relationships in RII-B and investigating the extent of homology and diversity between RII-B and RII-H, a peptide containing the autophosphorylation site of RII-B has been characterized. The phosphopeptide was rapidly (36 h) purified to homogeneity (yield = 40%) from a tryptic digest of RII B using three consecutive reverse-phase high performance liquid chromatography steps. A combination of gas-phase microsequencing and solid-phase Edman degradation was used to determine the sequence and to identify the phosphorylated site: Arg-Ala-Ser(P)-Val-Cys-Ala-Glu-Ala-Tyr-Asn-Pro-Asp-Glu-Glu-Glu-Asp-Asp-A la Glu. RII-B contains a classical phosphorylation site for the catalytic subunit, and the phosphopeptide sequence is homologous to the sequence surrounding the phosphorylation site of RII-H. Fourteen amino acids are identical in the two sequences, and the high net negative charge on the peptide is conserved. However, the peptide from RII-B is alanine-rich and more hydrophobic. Furthermore, five differences between the two functionally related sequences provide direct evidence for the idea that RII-B and RII-H are the products of related but distinct genes. PMID- 4030779 TI - Isolation and identification of delta 6-lithocholenic acid (3 alpha-hydroxy-5 beta-6-cholen-24-oic acid) as an intestinal bacterial metabolite of chenodeoxycholic acid in man. AB - Fecal bacterial biotransformation studies of chenodeoxycholic acid were performed. Incubations were carried out for 30-s to 12-h time intervals. delta 6 Lithocholenic acid was isolated by thin-layer chromatography. Its structure was confirmed by gas-liquid chromatography and mass spectrometry. The proportion of chenodeoxycholic acid biotransformed to delta 6-lithocholenic acid consistently ranged from 5.5 to 14.0%. PMID- 4030780 TI - Arachidonoyl-CoA synthetase. Separation from nonspecific acyl-CoA synthetase and distribution in various cells and tissues. AB - Arachidonoyl-CoA synthetase was solubilized from a particulate fraction of calf brain and human platelets using 1% Nonidet P-40 and 10 mM EDTA. Arachidonoyl-CoA synthetase from both preparations was separated from nonspecific (long chain) acyl-CoA synthetase (EC 6.2.1.3) by chromatography on hydroxylapatite. To further substantiate that the two acyl-CoA synthetases are distinct proteins, we solubilized enzyme from a mutant cell line lacking arachidonoyl-CoA synthetase and from the parent cell line from which it was derived. These preparations were chromatographed on hydroxylapatite, and the mutant showed an absence of the peak identified as arachidonoyl-CoA synthetase in the parent while retaining the peak of nonspecific acyl-CoA synthetase activity. We have also determined the levels of arachidonoyl and nonspecific acyl-CoA synthetase in 13 different human cells and tissues. Arachidonoyl-CoA synthetase is widely distributed and is present in significantly lower concentrations than nonspecific acyl-CoA synthetase only in adipose tissue and liver. PMID- 4030781 TI - Identification and characterization of ATP-dependent proton transport by rat liver multivesicular bodies. AB - Multivesicular bodies (MVB), prelysosomal organelles in the endocytic pathway, were prepared from estrogen-treated rat livers and examined for the presence of ATP-dependent proton transport. Vesicle acidification, assessed by acridine orange fluorescence quenching, was ATP dependent (ATP much greater than GTP, UTP), was enriched 25-fold over homogenate, was abolished by pretreatment with protonophores or a nonionic detergent, exhibited a pH optimum of 7.5, was inhibited by N-ethylmaleimide (NEM) (IC50 approximately 5 microM) and N,N' dicyclohexylcarbodiimide (IC50 approximately 5 microM), and was resistant to inhibition by vanadate, ouabain, and oligomycin. Acidification exhibited no specific cation requirement; however, maximal rates of acidification depended upon the presence of Cl- (Km approximately 20 mM). Other anions were less effective in supporting acidification (Cl- greater than Br- greater than much greater than gluconate, NO-3, SO2-4, and mannitol), and indeed NO-3 inhibited acidification even in the presence of 150 mM Cl-. The proton transport mechanism appeared to be electrogenic based on: (a) enhancement of acidification by valinomycin in the presence of K gluconate, and (b) ATP-dependent fluorescence quenching of bis(3-phenyl-5-oxoisoxasol-4-yl)pentamethine oxonol, a membrane potential-sensitive anionic dye. Furthermore, the magnitude of the pH and electrical gradients generated by the proton transport mechanism appeared to vary inversely in the presence and absence of Cl-. Finally, MVB exhibited ATPase activity that was resistant to ouabain and oligomycin, but was inhibited 32.3% by 1 mM NEM, 33.7% by 200 microM dicyclohexylcarbodiimide, and 18.7% by KNO3. In isolated MVB, therefore, the NEM-sensitive ATPase activity may represent the enzymatic equivalent of a proton pump. These studies identify and characterize an ATP-dependent electrogenic proton transport process in rat liver MVB which shares many of the properties of the proton pump described in clathrin-coated vesicles, endosomes, lysosomes, Golgi, and endoplasmic reticulum from liver and other tissues. Acidification of MVB differed somewhat from that of rat liver clathrin coated vesicles in response to Br- and NO-3, suggesting that membrane properties of these two organelles might differ. PMID- 4030782 TI - Galactoside-binding serum lectin of Xenopus laevis. Estrogen-dependent hepatocyte synthesis and relationship to oocyte lectin. AB - Xenopus laevis serum contains a lectin which binds alpha- and beta-galactosides. It was purified to homogeneity by affinity chromatography and consists of a single subunit with Mr approximately 69,000, associated in a multimer. The lectin is synthesized and secreted by hepatic parenchymal cells, and its synthesis is increased about 2-fold by estrogen treatment, both in vivo and in primary cell cultures. The serum lectin has the same carbohydrate binding properties as an oocyte lectin from X. laevis described previously, is immunologically cross reactive, and shows similarities in its peptide map. However, marked differences in amino acid composition preclude the possibility that the serum lectin is a precursor of the oocyte lectin. PMID- 4030783 TI - Equilibrium and rapid kinetic studies on nocodazole-tubulin interaction. AB - The interaction between nocodazole and calf brain tubulin in 10(-2) M sodium phosphate, 10(-4) M GTP, and 12% (v/v) dimethyl sulfoxide at pH 7.0 was studied. The number of binding sites for nocodazole was shown to be one per tubulin monomer of 50,000 as a result of equilibrium binding studies by gel filtration and spectroscopic techniques. The presence of microtubule-associated proteins did not significantly affect the binding of nocodazole to tubulin. The apparent equilibrium constant measured at 25 degrees C was (4 +/- 1) X 10(5) M-1. Temperature does not significantly affect the apparent equilibrium constant; hence, the binding of nocodazole to tubulin is apparently entropy driven. Stopped flow spectroscopy was employed to monitor the rate of nocodazole binding under pseudo first order conditions. The effects of temperature and nocodazole concentration were studied. The apparent rate constants were dependent on the concentration of nocodazole in a nonlinear manner. In conjunction with results from structural and thermodynamic studies the kinetic results were interpreted to suggest a mechanism of T + N in equilibrium with TN in equilibrium with T* N, where T and N are tubulin and nocodazole, respectively. T and T* represent two conformational states of tubulin. Furthermore, the kinetic data are consistent with the thermodynamic data only if a model of two parallel similar reactions were considered, one rapid and the other slow. The initial binding step for both the rapid and slow phases was characterized by identical binding constants; however, there was a significant difference in the rates of isomerization. Hence, nocodazole is potentially a useful probe for amplifying differences in solution properties of tubulin subspecies. PMID- 4030784 TI - Inhibition of intracellular degradation of proteoglycans by leupeptin in rat ovarian granulosa cells. AB - Previous work (Yanagishita, M., and Hascall, V. C. (1984) J. Biol. Chem. 259, 10270-10283) has indicated that heparan sulfate (HS) proteoglycans in rat ovarian granulosa cells are degraded by two kinetically distinct pathways. Pathway 1 degrades proteoglycans rapidly with a t 1/2 approximately 25 min without generating appreciable degradative intermediates. Pathway 2 degrades proteoglycans more slowly with a t 1/2 approximately 4 h, generating distinct degradative intermediates: single HS chains of Mr = approximately 10,000 and approximately 5,000. Effects of leupeptin, an inhibitor of thiol proteases, on the intracellular degradation of proteoglycans in the rat ovarian granulosa cell culture were examined using various chase protocols after labeling cells with [35S]sulfate. The presence of leupeptin at 100 micrograms/ml in the culture medium inhibited the intracellular degradation of proteoglycans by approximately 80% during a 7-h chase period after a 20-h labeling. Leupeptin affected neither the cellular content nor the in vitro activities of beta-hexosaminidase and arylsulfatase. Structural analyses of heparan sulfate species in leupeptin treated cells demonstrated that the drug inhibited the degradation of HS proteoglycans at two distinct points. First, degradation of the core protein was partially inhibited and delayed before the start of glycosaminoglycan degradation. This resulted in the accumulation of degradative intermediates with partially degraded core proteins bearing intact glycosaminoglycan chains. This establishes the initial sequence for HS proteoglycan degradation, with proteolysis preceding endoglycosidase digestion, and suggests that these two degradation steps may occur in physically separate compartments. Second, the final depolymerization of HS fragments through pathway 2 was totally inhibited, resulting in the continuous accumulation of Mr = 5,000 HS chains. This is not due to the direct inhibition of the lysosomal exoglycosidase and sulfatase enzymes responsible for the complete depolymerization of HS chains, since pathway 1, while slowed, continued to completely depolymerize the HS chains in the presence of leupeptin. The results suggest that the intracellular compartment which completely degrades heparan sulfate chains is separate from those containing partially, endoglycosidically processed heparan sulfate chains and that leupeptin interfered with the translocation of glycosaminoglycans to the final degradation site. PMID- 4030785 TI - Anomeric and other substrate specificity studies with myo-inositol-1-P synthase. AB - L-myo-Inositol-1-phosphate synthase has been found to have at least a 5-fold preference for the beta-anomer of its natural substrate D-Glc-6-P. The alpha anomer appears to be an inhibitor of the reaction and may be converted to product as well. As well as showing an enzymatic preference for the equatorial C-1 hydroxyl of D-Glc-6-P, our results suggest that it is the pyranose form of D-Glc 6-P that binds to the enzyme and that ring-opening is an enzymatic step. We have also found D-2-dGlc-6-P, D-2-F-2-dGlc-6-P, and D-Man-6-P each to be both competitive inhibitors and substrates that are converted to inositol phosphates by the synthase. D-Allose-6-P is a weak inhibitor of the enzyme, but not a substrate. D-Gal-6-P is neither substrate nor inhibitor. Thus the specificity of the synthase with respect to single position epimers of D-Glc-6-P increases in the order C1 less than C2 much less than C3 less than C4. PMID- 4030786 TI - Activation, aggregation, and product inhibition of cobra venom phospholipase A2 and comparison with other phospholipases. AB - The kinetics of phospholipid hydrolysis by cobra venom phospholipase A2 were examined and compared to those of phospholipase A2 from porcine pancreas, Crotalus adamanteus (rattlesnake) venom, and bee venom. Only the enzyme from Naja naja naja (cobra) venom was found to be activated significantly by phosphorylcholine-containing compounds when hydrolyzing phosphatidylethanolamine. The cobra venom enzyme was also the only one in which these activators induced protein aggregation. The parallel specificity for activators and aggregators suggests that these two phenomena are linked. Product effects were also shown to vary between these four phospholipases. These effects manifest themselves in nonlinear time courses, in changes in steady state velocity, and in the differential effects of serum albumin on reaction rates. Different effects were even seen for the same enzyme when acting on different substrates. A model is presented to account for these observations; its main features are enzyme activation by an activator molecule, whose specificity depends on the enzyme, and an activator-induced aggregation of the enzyme. PMID- 4030787 TI - Experimental evidence for the contractile activities of Acanthamoeba myosins IA and IB. AB - The low-shear viscosity of 5-30 microM F-actin was greatly increased by the addition of 0.1-0.5 microM unphosphorylated Acanthamoeba myosins IA and IB. The increase in viscosity was about the same in 2 mM ADP as in the absence of free nucleotide but was much less in 2 mM ATP. The single-headed monomolecular Acanthamoeba myosins were as effective as an equal molar concentration of two headed muscle heavy meromyosin and much more effective than single-headed muscle myosin subfragment-1. These results suggest that Acanthamoeba myosins IA and IB can cross-link actin filaments as proposed in the accompanying paper (Albanesi, J. P., Fujisaki, H., and Korn, E. D. (1985) J. Biol. Chem. 260, 11174-11179) to explain the actin-dependent cooperative increase in actin-activated Mg2+-ATPase activity as a function of the concentration of myosin I. Superprecipitation occurred when phosphorylated myosin IA or IB was mixed with F-actin. In addition to myosin I heavy chain phosphorylation, superprecipitation required Mg2+ and ATP. ATP hydrolysis was linear during the time course of the superprecipitation, and inhibitors of ATP hydrolysis inhibited superprecipitation. A small, dense contracted gel was formed when the reaction was carried out in a cuvette, and a birefringent actomyosin thread resulted from superprecipitation in a microcapillary. The rate and extent of superprecipitation depended on the actin and myosin I concentrations with maximum superprecipitation occurring at an actin:myosin ratio of 7:1. These results provide strong evidence for the ability of Acanthamoeba myosins IA and IB to perform contractile and motile functions. PMID- 4030788 TI - Isozymes of bovine intestinal alkaline phosphatase. AB - Alkaline phosphatases from calf and bovine small intestines have been isolated in homogeneous form from both mucosa and luminal contents. The detergent-solubilized calf enzyme resolves into two peaks of activity, C-1 and C-2, on chromatofocusing. Only one of these activity peaks is present in the enzyme from the adult animal. Amino acid compositions, N-terminal sequences, and tryptic peptide maps show that C-1 and C-2 are isozymes of differing primary structure and that the adult form of the enzyme is identical to C-2. The developmentally controlled expression of the two isozymes reported here suggests a molecular basis for the previous indications that functional changes in intestinal alkaline phosphatase occur with tissue maturation. The sugar composition of the carbohydrate chains of these isozymes has been determined and enzymatic deglycosylation with endo-beta-N-acetylglucosaminidase-F indicates two N-linked and one or more O-linked glycoconjugates/monomer. PMID- 4030789 TI - Purification and some properties of the glycolipid transfer protein from pig brain. AB - A glycolipid-specific lipid transfer protein has been purified to apparent homogeneity from pig brain post-mitochondrial supernatant. The purified protein was obtained after about 6,000-fold purification at a yield of 19%. Evidence for the homogeneity of the purified protein includes the following: (i) a single band in acidic gel electrophoresis, in sodium dodecyl sulfate-gel electrophoresis, (ii) a single band in analytical gel isoelectric focusing, (iii) exact correspondence between the glycolipid transfer activity and stained protein absorbance in the acidic gel electrophoresis, and (iv) coincidence between the transfer activity and protein absorption at 280 nm in gel filtration through Ultrogel AcA 54. The protein has an isoelectric point of about 8.3 and a molecular weight of 22,000, as measured by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. A molecular weight of 15,000 was calculated from AcA 54 gel filtration. The amino acid composition has been determined. The protein binds [3H]galactosylceramide but not [3H]phosphatidylcholine. Under the conditions used, 1 mol of the transfer protein bound about 0.13 mol of [3H]galactosylceramide. The glycolipid transfer protein-[3H]galactosylceramide complex was isolated by a Sephadex G-75 chromatography. An incubation of the complex with liposomes resulted in the transfer of [3H]galactosylceramide from the complex to the acceptor liposomes. The result indicates that the complex functions as an intermediate in the glycolipid transfer reaction. The protein facilitates the transfer of [3H]galactosylceramide from donor liposomes to acceptor liposomes lacking in glycolipid as well as to acceptor liposomes containing galactosylceramide. PMID- 4030790 TI - Mechanism of interferon action. Purification and substrate specificities of the double-stranded RNA-dependent protein kinase from untreated and interferon treated mouse fibroblasts. AB - The double-stranded RNA (dsRNA)-dependent protein kinase which catalyzes the phosphorylation of ribosome-associated protein P1 and the alpha subunit of eukaryotic protein synthesis initiation factor 2 (eIF-2) was purified and characterized from mouse fibroblast L929 cells treated with either natural or recombinant interferon and from untreated cells. The dsRNA-dependent P1/eIF-2 alpha kinase was purified at least 1,500-fold from interferon-treated cells; the kinase activity that catalyzed the phosphorylation of eIF-2 alpha copurified with protein P1. The yield of P1/eIF-2 alpha protein kinase activity obtained following purification from cells treated with interferon was about 5-10 times greater than the yield from an equivalent number of untreated cells. The purified protein kinase remained dsRNA dependent. When P1 kinase was activated by dsRNA, a major phosphopeptide designated Xds was phosphorylated; Xds was not phosphorylated from P1 which had not been activated by dsRNA. The apparent native molecular weight of the purified mouse L929 dsRNA-dependent kinase as determined by sedimentation analysis was about 62,000, comparable to the molecular weight of 67,000 determined for denatured L929 phosphoprotein P1 by sodium dodecyl sulfate polyacrylamide gel electrophoresis. The purified protein kinase was highly selective for the alpha subunit of protein synthesis initiation factor eIF-2 and endogenous protein P1. Kinase activity was dependent upon Mg2+, and the Km for ATP was determined to be 5 X 10(-6) M. Histones (H1, H2A-B, H3, and H4) and protein synthesis initiation factors other than eIF-2 (eIF-3, eIF-4A, eIF-4B, and eIF-5) were not substrates or were very poor substrates for the purified dsRNA dependent protein kinase. N-Ethylmaleimide, ethylenediaminetetraacetic acid, AMP, pyrophosphate, spermine, spermidine, and high concentrations of potassium inhibited both P1 and eIF-2 alpha phosphorylation by the purified kinase, whereas ethylene glycol bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid and phenanthroline did not significantly affect the phosphorylation of either protein P1 or eIF-2 alpha. PMID- 4030791 TI - A transcription factor required for promoter recognition by human mitochondrial RNA polymerase. Accurate initiation at the heavy- and light-strand promoters dissected and reconstituted in vitro. AB - Faithful transcription of human mitochondrial DNA has been reproduced in vitro, using a fraction of mitochondrial proteins capable of accurate initiation at both the heavy- and light-strand promoters. Here we report the initial dissection of this system into two nonfunctional components which, upon mixing, reconstitute promoter-specific transcriptional capacity in vitro. One of these components copurifies with the major nonspecific RNA polymerase activity, suggesting its identity. The other component lacks significant polymerase activity, but contains a protein or proteins required for accurate initiation at the two individual promoters by isolated mitochondrial RNA polymerase. This factor facilitates specific transcription, but has little or no effect on nonspecific transcription of a synthetic copolymer (poly(dA-dT)), indicating a positive role in proper promoter recognition. The transcription factor markedly stimulates light-strand transcription, but only moderately enhances transcription initiation at the heavy strand promoter, suggesting different or additional factor requirements for heavy strand transcription. These requirements may reflect the functional differences between heavy- and light-strand transcription in vivo and, in particular, the role of the light-strand promoter in priming of heavy-strand DNA replication. PMID- 4030792 TI - Studies on the reactivity of the essential sulfhydryl groups as a conformational probe for the fatty acid synthetase of chicken liver. Inactivation by 5,5' dithiobis-(2-nitrobenzoic acid) and intersubunit cross-linking of the inactivated enzyme. AB - Fatty acid synthetase of chicken liver is rapidly and reversibly inactivated by 5,5'-dithiobis-(2-nitrobenzoic acid) (DTNB) at a rate (k2 = 132 mM-1 S-1 in 3 mM EDTA, 1% (v/v) glycerol, pH 7.0, at 25 degrees C) up to 2200 times higher than the reaction of this reagent with simple thiol compounds. The inactivation is caused by the reaction of the phosphopantetheine SH group, since it is protected competitively by either acetyl- or malonyl-CoA, and since the inactivated enzyme is unreactive with the phosphopantetheine label chloroacetyl-CoA but reactive with the cysteine reagent 1,3-dibromopropanone. Moreover, chloroacetyl-CoA prevents the modification of the rapidly reacting essential SH group by DTNB. The number of SH groups involved in inactivation was determined by correlating activity loss with the extent of reaction and by stopped-flow analysis of substrate (or chloroacetyl-CoA) protection. Values between 0.91 and 1.15 SH groups/dimer were obtained, indicating the presence of substoichiometric amounts of the prosthetic group in the fatty acid synthetase preparations used in this study. Inactivation of the synthetase by DTNB is strongly inhibited by increasing salt concentration and protected noncompetitively by NADP+ and NADPH. Treatment of the enzyme inactivated at low salt by salt, NADP+, or NADPH also effectively reduced cross-linking between enzyme subunits. The parallel effects of these treatments on the reaction with DTNB and subsequent dimerization are consistent with a minimum model of two discreet conformation states for fatty acid synthetase. In the low salt conformer, the phosphopantetheine and cysteine SH groups are juxtaposed, and the DTNB reaction (k2 approximately 132 mM-1 S-1) and dimerization are both facilitated. Transition to the high salt conformer by the above treatments is accompanied by an approximately 20-fold reduction of reactivity with DTNB (k2 = 6.8 mM-1 S-1) and reduced dimerization, due to spatial separation of the SH groups. During palmitate synthesis, the enzyme may oscillate between these conformation states to permit the reaction of intermediates at different active sites. Results obtained by studies on the effect of pH on DTNB inactivation implicate a pK of 5.9-6.1 for the essential SH group independent of salt concentration. This value is 1.5-1.8 pH units lower than the pK of 7.6-7.7 for CoA and may explain the 23-fold increase of the rate constant from a value of 0.3 mM-1 S-1 for CoA to that of the high salt conformer. PMID- 4030793 TI - Loss of preservative from a tuberculin solution in rubber stoppered vials fastened with different seals. AB - A tuberculin purified protein derivative (PPD) solution containing 0.3% phenol as a preservative was dispensed in glass vials closed with rubber stoppers fastened in three different ways, namely with Tear-off seals, Flip-off seals and partial seals. After various times of storage at 5 degrees C and 37 degrees C, the phenol content in the tuberculin solution was determined. It was found that the Flip-off seals allowed the phenol to escape at a faster rate than the Tear-off seals and that vials closed with partial seals showed the highest loss of phenol. Although these losses were much more pronounced at 37 degrees C than at 5 degrees C, the phenol content at the latter temperature was, over a period of three years, within the limits of acceptability for tuberculin products capped with Tear-off or Flip-off seals. A loss of phenol also occurred from tuberculin solution stored at -28 degrees C in vials capped with either Tear-off or partial seals. In addition to the Tear-off and Flip-off seals other seals such as the "controlled score' Flip-off seal and the Alcoa Steri-Twist cap were evaluated for their imperviousness to air. Except for the Alcoa Steri-Twist cap none of the seals we have investigated were air tight and hence entirely satisfactory to prevent losses of phenol by evaporation from tuberculin products.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4030794 TI - Immunogenicity of hepatitis B vaccine in guinea-pigs, mice and man. AB - The immunogenicity of the hepatitis B vaccine Hevac B Pasteur was assayed in guinea-pigs. The reproducibility of the test was determined by comparing the ImD50 of two samples of vaccine in 12 and eight groups of 40 animals each. The variation coefficient between groups was approximately 30%, similar to that found for other vaccines assayed in biological tests in vivo. The sensitivity of the test was determined by comparing the dose response curves in mice, guinea-pigs and humans. The results showed that one ImD50 in man (after one injection) was approximately equivalent to 3 ImD50 in guinea pigs and to 100 ImD50 in Balb/C mice. Stability of Hevac B at 37 degrees C was assayed by determining in guinea pigs the ImD50 of a series of samples of vaccine that had been incubated at 37 degrees C for varying amounts of time. The immunogenicity of the vaccine was found to decay with a half-life of ten to 15 days at 37 degrees C. PMID- 4030795 TI - An investigation of a mouse model to estimate the potency of the diphtheria component in vaccines. AB - A mouse model to estimate the potency of the diphtheria toxoid components in vaccines using Vero cells to detect the neutralizing antibodies in the sera from immunized mice is described. The results obtained with this mouse model correlated significantly with those obtained in the lethal challenge test in guinea-pigs. For this reason it is suggested that the potency test in guinea-pigs be replaced by this mouse model because a considerable reduction in the number of animals used and costs can be achieved by the introduction of this mouse test for the routine control of the potency of the diphtheria component of vaccines. PMID- 4030797 TI - Force, velocity and energy flow during the overarm throw in female handball players. AB - The overarm throw of 56 female handball players was analysed cinematographically. The time courses of the ball velocity, the force on the ball, the energy flow to the ball as well as the velocities of wrist, elbow and hip were calculated. The mean ball velocity at release was 17.2 m s-1. The major part (73%) of the work on the ball appeared to be done in the last 50 ms of the throw. It is shown that high maximal segmental velocities are important pre-requisites for an optimal flow of energy to the ball during that last phase of the throw. The consecutive actions of body segments from larger proximal segments to the relatively smaller distal segments seem to be connected to intrinsic muscle properties and to a flow of energy from proximal to distal segments. PMID- 4030796 TI - A new 23 valent pneumococcal vaccine: immunogenicity and reactogenicity in adults. AB - A 23 valent pneumococcal vaccine containing 25 micrograms of each polysaccharide was administered to 30 healthy adults. Adverse reactions were always mild, consisting only of local pain and erythema in most subjects. Pre- and four weeks post-vaccination sera were analysed by radioimmunoassay. Geometric mean titre (GMT) ratios were between 2.3 and 14.3 (overall mean X 5.7) according to type. A level of 300 ng of antibody N/ml, the supposedly protective level, was achieved in at least 86.6% of the subjects for all the serotypes. PMID- 4030798 TI - The measurement of shock waves following heel strike while running. AB - A non-invasive method for demonstrating the shock wave which propagates through the skeletal system following heel strike is described. This wave was not seen in force plate studies where adequate shock absorption was provided by running shoes. In the present study six subjects ran across a force plate without shoes before and after they were fatigued on a treadmill to demonstrate possible changes in the heel strike transient. Most of the parameters measured were not altered by fatigue, and a relationship between the shock wave and height, but not the weight of the runner was demonstrated. The different mechanisms leading to this phenomenon, and its implication in the areas of osteoarthritic degeneration and running mechanics are discussed. PMID- 4030799 TI - Kinematic features of wheelchair propulsion. AB - Three male paraplegics volunteered to push their wheelchairs on a motor driven treadmill, for a total of 80 min each, at a work rate of 60-65% of their VO2 maximum, determined on an earlier test session. At 20 min intervals 16 mm high speed film of the subjects was taken for three consecutive push cycles. The digitized film was used to compute the angular kinematics of the shoulder and elbow joints, the variations in the position of the trunk (as measured by a marker on the neck) and hand relative to the axle of the rear wheel. There were no intrasubject variations over the 80 min testing period for any of the recorded variables. This was interpreted as implying that at that work rate, fatigue was not exhibited as variations in the kinematics of movement. There were considerable differences between the style of one subject when compared to the other two over all the trials of each subject. This variation in style was most obvious in subject number PT who had a pumping style of push and recovery whereas subjects CA and GW employed a more continuous circular motion. The differences in the amount of forward lean of each subject were related to residual muscle strength. The discussion centered on the influence of the different styles on performance. PMID- 4030800 TI - Modification of spastic gait through mechanical damping. AB - The effect of dissipative mechanical loads on spastic gait has been studied, to evaluate the feasibility of using mechanically damped orthoses to effect functional improvements in the gait of spastic patients. This concept is based on a hypothesis citing uninhibited, velocity-dependent stretch reflexes as a possible causal factor in spastic gait abnormalities, such as equinus and back kneeing. In order to screen potential experimental subjects and to quantify velocity-dependent reflex behaviour, ankle rotation experiments and filmed gait analysis were performed. The results supported the existence of a velocity threshold. Orthosis simulation experiments were performed with one spastic subject, using a wearable, computer-controlled, electromechanical, below-knee orthosis simulator to apply a variety of damping loads to the ankle as the subject walked. Results indicated that appropriate damping can improve local joint kinematics. The damping causes a reduction in muscle stretch velocity which apparently results in reduced spastic reflex activity. PMID- 4030801 TI - Quantitative calculations of temporomandibular joint reaction forces--II. The importance of the direction of the jaw muscle forces. AB - The effect of error in determination of muscle force direction on quantitative calculation of the temporomandibular joint reaction force was investigated in a two-dimensional, two-muscle model. A computer program using the model incremented the direction of the temporalis and masseter muscle force vectors and generated a family of curves showing the relationship between muscle force direction and the direction and magnitude of the temporomandibular joint reaction force. The major effect of muscle force direction is its influence on the length of the muscle force moment arm. The analyses show that calculation of the joint reaction force is much more sensitive to errors in muscle force direction than to muscle force magnitude. Calculation of the magnitude of the joint reaction force is less sensitive to error than the calculation of joint reaction force direction. An error of 1 degree in muscle force direction could produce a 2 degrees error in joint force direction. No ideal location of the muscle force vectors was found. Vector positions that enhanced calculation of joint force magnitude increased the sensitivity to errors when calculating joint force direction. The difficulties of precisely determining muscle force directions are discussed. The present results indicate that a two-muscle model requires very precise determination of muscle force directions to reliably calculate the temporomandibular joint reaction forces. PMID- 4030802 TI - Arterial steal phenomenon in femoro-tibial bypass with arterio-venous shunt. AB - Arterio-venous shunts are sometimes constructed at the distal anastomosis of femoro-tibial bypass grafts in order to increase blood flow velocity within the graft. However, the use of such a shunt may "steal' blood from an already ischaemic distal arterial bed. The aim of this study was to determine the conditions under which this might happen. Experiments were carried out on an in vitro model of the femoro-tibial bypass under steady flow conditions. The simple resistance model of Hyman and Brewer (J. Biomechanics 13, 469-675, 1980), modified to take into account the nonlinear pressure flow relationship through a stenosis, was used to interpret experimental data. Good agreement was obtained between measured and calculated steal. PMID- 4030803 TI - Objective determination of anatomical landmarks on the body surface: measurement of the vertebra prominens from surface curvature. AB - A method for the objective detection of anatomical landmarks on the body surface is presented. The method is based on an analysis of local surface shape which is described in terms of surface curvature. The curvature is calculated from the surface coordinates as measured by optical methods such as moire topography or rasterstereography. As an example, the location of the vertebra prominens is determined. In order to assess the accuracy and reliability of the procedure, the results are compared with the conventional method of palpation and marking. The measured deviations are in the order of a few millimeters. PMID- 4030804 TI - Flow of couple stress fluid through stenotic blood vessels. AB - The effects of an axially symmetric mild stenosis on the flow of blood, when blood is represented by a couple stress fluid model, have been studied. It is found that, for a fixed stenosis size, the resistance to flow and wall shear stress increase as the couple stress parameter eta decreases from unity. A comparison of the results with those of the Newtonian case shows that the magnitude of resistance to flow and wall shear under a given set of conditions, is greater in the case of the couple stress fluid model. It is seen that even in the case of a mild stenosis (19% area reduction), resistance to flow and wall shear values are increased over those for no stenosis by 60% and 62%, respectively, when compared with the case of a Newtonian fluid. PMID- 4030805 TI - Geometry and motion of the knee for implant and orthotic design. AB - By analysing sections of distal femurs in the computer, and by making direct measurements, the posterior femoral condyles were shown to closely fit spherical surfaces. The center of the spheres were then used as reference points and used to define reference axes in a motion study. In flexing from 0 to 120 degrees the medial femoral condyle moved little, the lateral moved posteriorly by 17 mm, and there was an axial rotation of 20 degrees. The data were applied to implant and orthotic design and evaluation. PMID- 4030806 TI - Moire patterns: an accurate technique for determination of the locus of the centres of rotation. AB - This study describes an accurate technique for the determination of the centre of rotation of small angles. The moire fringe method localizes the centre of rotation by defining two primary fringes, each of which is found by the intersection of three lines. The primary fringes intersect at the centre of rotation at 90 degrees to each other, the angle least likely to produce an error in measurement. By utilizing joints with known centres of rotation, we have found that the method is extremely accurate and reproducible to within 2 mm of the real centre for angular changes as small as 3 degrees. This technique is useful in evaluating whether a joint is a simple hinge, i.e. rotating about a single axis of rotation or whether the joint moves about a changing axis of rotation referred to as a locus or centrode. PMID- 4030807 TI - A multipurpose tissue bending machine. AB - A unique tissue bending machine was developed to test the bending properties of normal and bioprosthetic heart valve material. It can be operated in air or in a tissue bath and can measure bending torques with an accuracy in excess of 1.0 microN m. Three contrasting substances were tested to compare their stiffness and to demonstrate the machine. PMID- 4030808 TI - Abstracts of the fourth meeting of the European Society of Biomechanics. Davos, Switzerland, 24-26 September 1984. PMID- 4030809 TI - Fertility and social class in a French village, 1901-75. PMID- 4030810 TI - Fertility of couples following cessation of contraception. PMID- 4030811 TI - Factors affecting fertility in four Muslim populations: a multivariate analysis. PMID- 4030812 TI - The changing pattern of contraception in Lahore, Pakistan: 1963-80. PMID- 4030813 TI - Factors related to delay for legal abortions performed at a gestational age of 20 weeks or more. PMID- 4030814 TI - Influence of maternal age, parity and social class on perinatal mortality in Scotland: 1960-82. PMID- 4030816 TI - Visual acuity of the Gidra in lowland Papua New Guinea. PMID- 4030815 TI - Infant and child mortality in Pakistan--some trends and differentials. PMID- 4030817 TI - Trends and differentials in Moslem fertility. A comment. PMID- 4030818 TI - Epidemiology, genetics and sociology. A comment. PMID- 4030819 TI - Total condylar knee replacement. A study of factors influencing range of motion as late as two years after arthroplasty. AB - The factors influencing the range of motion of the knee after total condylar knee replacement were analyzed in fifty-five consecutive patients who had seventy-one replacements and a minimum follow-up of two years. Statistically significant improvement in flexion occurred between the first postoperative evaluation in the hospital, the evaluation at discharge, and the evaluations at three months and one year after replacement. Postoperative range of motion was not influenced by the patient's gender, by the extent of the disease (monoarticular in comparison with polyarticular), or by treatment with a unilateral or bilateral procedure. The knees of patients with rheumatoid arthritis gained extension at the expense of flexion. The average flexion arcs of the knees with rheumatoid arthritis and of those with osteoarthritis were the same two years after operation as they had been preoperatively. Knees with preoperative flexion of more than 100 degrees had lost flexion at follow-up, whereas those with preoperative flexion of less than 100 degrees had gained flexion. Significant improvement in extension occurred only before discharge. For the patients whose preoperative flexion contracture was 10 degrees or more, virtually all improvement in the contracture occurred at the time of surgery. Patients who had a simultaneous bilateral total knee replacement did as well as those with a single knee replacement.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4030820 TI - Results of compression-plating of closed Galeazzi fractures. AB - Diaphyseal fractures of the distal third of the radius that are associated with disruption of the distal radio-ulnar joint accounted for eighty-four (6.8 per cent) of 1236 fractures in the forearm that were treated during a five-year period at the Los Angeles County-University of Southern California Medical Center. Thirty-six closed Galeazzi fractures, twenty-eight in male and eight in female patients, were followed for 1.5 to seven years after treatment using standard AO-compression plates with four to seven holes. Complications included seven injuries to the sensory or dorsal interosseous branch of the radial nerve, two infections, two non-unions, two re-fractures after plate removal, and shortening of the radius of five millimeters in one patient. The complication rate was 39 per cent. The average grip strength at follow-up was 71 per cent of the calculated normal value. The loss of strength was not related to use of a volar or dorsal surgical approach, the patient's age, or a delay of surgery for more than ten days after injury. The average loss of grip strength in the seven upper extremities with restricted motion of the wrist and forearm was 48 per cent, compared with an average loss of 29 per cent in the whole group. Of the twelve patients who were operated on more than ten days after injury, six had loss of motion at follow-up, compared with three who had such a loss among the twenty-four patients who were operated on within ten days after injury.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4030822 TI - Anterior cruciate reconstruction using the Jones-Ellison procedure. AB - We performed a follow-up study of forty consecutive combined Jones-Ellison anterior-cruciate reconstructions in a young, athletic population. The mean interval from injury to operation was 2.7 years. Preoperatively, all patients had a 3+ or 4+ pivot shift and instability. All but five patients had a meniscal tear, and thirty patients had arthritic changes in the knee at the time of operation. Postoperatively only four of the patients had any complaints of giving way. Although thirty of the patients returned to their previous sports activities, only eight achieved the preinjury level of performance. Arthritic symptoms were present at operation in thirty patients, while thirty-four had no postoperative objective signs of pivot shift or instability. PMID- 4030821 TI - Treatment of sciatic denervation disuse osteoporosis in the rat tibia with capacitively coupled electrical stimulation. Dose response and duty cycle. AB - We determined the dose-response characteristics of a low-voltage, high-frequency, capacitively coupled electrical signal that reverses an established osteoporosis in a rat tibial model with sciatic neurectomy. The electrical signals were delivered by means of stainless-steel gel-coated electrodes. In the first part of the study, the shape (sine wave) and frequency (sixty kilohertz) of the signal were kept constant while the voltage was varied from 0.01 to ten volts, peak to peak. Control osteoporotic and sham osteoporotic animals showed a mean loss of tibial ash weight of 19 and 17 per cent, respectively, twenty-eight days after sciatic neurectomy plus twelve days of no treatment using sham electrodes. Rats that were subjected to 0.25, 0.50, 1.0, 2.5, and 5.0 volts, peak to peak, for twelve days beginning on the twenty-eighth day after sciatic neurectomy all showed mean losses of tibial ash weight that were significantly less than those of the controls. The rats that had a 0.5-volt peak-to-peak signal showed the least mean loss of tibial ash weight (only 6 per cent). We concluded that a capacitively coupled electrical signal, delivered through gel-coated electrodes, can largely reverse an established disuse osteoporosis due to neurectomy in the rat tibia. In the second part of the study, the duty cycles of a sine-wave, sixty kilohertz, 0.5-volt peak-to-peak signal were varied (12.5, 50, and 100 per cent on), and the wet, dry, and ash weights were determined and compared with those of unstimulated osteoporotic controls. Only the 100 per cent duty-cycle signal was effective in reversing the loss of bone mass in the neurectomized tibiae. PMID- 4030823 TI - The lower-extremity musculature in chronic symptomatic instability of the anterior cruciate ligament. AB - We studied the musculature of the lower extremity in forty-one patients with chronic symptomatic instability of the anterior cruciate ligament. Computed tomographic and clinical measurements of the limb were taken at levels fifteen and twenty-five centimeters proximal to the medial joint line and ten centimeters distal to it. Biopsy specimens from the vastus lateralis of both lower extremities were analyzed by histochemistry and electron microscopy. Computed tomography revealed a decrease in the muscle square area of the affected thigh of 8 per cent as compared with the control lower extremity. There was quadriceps atrophy of 10 per cent and hamstrings atrophy of only 4 per cent. The atrophy of the vastus medialis was significantly greater than that of the entire quadriceps. Histochemistry revealed a similar decrease in fiber size for all fiber types, and hence no shift in fiber type. Electron microscopy showed an increase in intracellular fat but no change in mitochondrial volume density or capillarization. PMID- 4030824 TI - Complete subtalar release in club feet. Part I--A preliminary report. AB - The complete subtalar release is an extensive soft-tissue procedure for the treatment of club foot that non-surgical methods have not corrected. It is a more extensive surgical procedure than others currently in use. Two advantages of this procedure are that it produces a greater degree of correction than other procedures and that it provides superior alignment between the foot and leg. The main disadvantage is a tendency to overcorrection. In this report I present the steps in performing the procedure and the anatomical concept on which it is based. PMID- 4030825 TI - Complete subtalar release in club feet. Part II--Comparison with less extensive procedures. AB - A comparison of the complete subtalar release with less extensive soft-tissue releases in the treatment of idiopathic club foot was done in two groups of patients. Group I consisted of seventeen patients (twenty-six feet), of whom fourteen patients (twenty-one feet) had a posteromedial and lateral release. Group II consisted of seventeen patients (twenty-five feet) who had a complete subtalar release. All patients were followed for a minimum of two years. The complete subtalar release provided a higher percentage of both radiographically and clinically satisfactory results than did the less extensive soft-tissue procedures, but with the former procedure there was a tendency to overcorrection unless the bones were precisely repositioned at the end of the procedure. PMID- 4030827 TI - Guidelines for the use of digital tourniquets based on physiological pressure measurements. AB - A potential complication of a digital tourniquet is neurovascular damage due to excessive tissue pressure. A technique for measuring digital tourniquet pressures was developed in our laboratory and was tested on fresh cadaver hands in order to establish guidelines for proper application of tourniquets. A saphenous vein from a fresh cadaver was laid subcutaneously along the neurovascular bundle of the test finger. Digital tourniquets consisting of Penrose drains or rolled surgical gloves were then applied in a standardized fashion. Saline solution was injected through the saphenous vein in a quasi-static fashion using a Harvard pump, and the pressure within the vein was monitored with a pressure transducer. When the pressure within the vein reached the closing pressure generated by the tourniquet, the pressure stabilized due to leakage of fluid beyond the tourniquet. Digital tourniquets applied in customary fashion by selected physicians and surgeons produced a wide range of closing pressures that did not exceed 360 millimeters of mercury. Rolled surgical gloves produced closing pressures ranging from 113 to 363 millimeters of mercury, depending on the relationship between the size of the glove and that of the hand. Penrose drains produced closing pressures of more than 800 millimeters of mercury, depending on the amount of stretch applied. PMID- 4030826 TI - Results of revision for mechanical failure after cemented total hip replacement, 1979 to 1982. A two to five-year follow-up. AB - From January 1979 to February 1982, 143 patients (seventy-nine women and sixty four men) with 146 uninfected cemented total hip arthroplasties had revision cemented hip arthroplasty at The Hospital for Special Surgery for what was considered to be mechanical failure. The average age of the patients at primary arthroplasty was 56.1 years and at revision, 62.1 years. Loosening of the femoral component before revision correlated with varus positioning in 50 per cent of the hips, inadequate cement in 34 per cent, and a relatively young age in 16 per cent. The average age of the patients (fifteen hips) with a loose femoral component that had been placed in a neutral or valgus position with good cementing technique was 48.2 years at the time of primary arthroplasty. Loosening of the acetabular component was attributed to high placement of the cup in 41 per cent, inadequate bone in 18 per cent, a vertical orientation of the opening of the cup in 7 per cent, and poor cementing technique in 3 per cent. Complications associated with revision included perforation of the femoral cortex in 13 per cent, postoperative deep infection in 3.4 per cent, postoperative dislocation in 8.2 per cent, trochanteric complications in 6.2 per cent, and sciatic palsy in 0.7 per cent. Of the 139 hips that were followed for an average of 3.6 years (range, two to five years) after revision, the results were excellent in 59 per cent, good in 7 per cent, fair in 16 per cent, and poor in 18 per cent. After revision of the 139 hips, 29 per cent showed progressive radiolucencies; 18 per cent, femoral subsidence; and 9 per cent, acetabular migration. Definite mechanical failure after revision was identified in 15.8 per cent of the hips. These failures were due to loosening in 12.2 per cent of the hips, femoral fracture in 2.2 per cent, and disabling dislocation in 1.4 per cent. At the time of follow-up, twelve hips (8.6 per cent) had been revised a second time: six (4.3 per cent) for loosening of one or both components, three (2.2 per cent) for femoral fracture, and three (2.2 per cent) for infection. Mechanical failure and progressive radiolucencies were associated with poor quality of bone (p less than 0.001) and inadequate anatomical reconstruction (p less than 0.03). PMID- 4030828 TI - Non-union of fractures of the sternum. AB - Injuries to the sternum and thoracic cage are relatively frequent in this age of motor-vehicle accidents, high-speed sports activities, and industrial injuries, yet non-union of a fracture of the sternum is exceptionally rare. Sternotomy is commonly performed in cardiothoracic surgery, and the sternum is usually divided vertically or transversely, but non-union of the sternal cut is rare. Fracture of the sternum in a child is especially rare. PMID- 4030829 TI - The effect of adjunctive methylmethacrylate on failures of fixation and function in patients with intertrochanteric fractures and osteoporosis. AB - In a retrospective review of eighty-two intertrochanteric fractures (twenty-nine stable and fifty-three unstable) in seventy-nine elderly, debilitated patients with associated advanced osteoporosis (Grade III or less by the system of Singh et al.), fifty-six were available for follow-up: twenty-eight that had been treated at the University of Illinois with an approximately anatomical reduction and compression-screw fixation and twenty-eight (in twenty-seven patients) that had been treated at the University of Chicago with an approximately anatomical reduction, compression-screw fixation, and adjunctive methylmethacrylate bone cement in the head-neck fragment. Follow-up analysis after an average of thirty four months for the group that had augmentation with cement and an average of twenty-six months for the uncemented group showed that for the eighteen stable fractures that could be followed the rates of complications of fixation were the same in the two groups, while for the thirty-eight unstable comminuted fractures that were followed the rate of complications of fixation was lower when adjunctive methylmethacrylate cement was used. Among the unstable fractures, one failure (in twenty-one fractures) in the cement-augmented group and ten failures (in seventeen fractures) in the uncemented group were due to failure of fixation (p less than 0.01). For reasons that are not clear, when the thirty-two patients with a healed fracture who could be evaluated for function were rated using the Iowa hip score, the nineteen who were treated with adjunctive cement had significantly lower scores than did the thirteen who were treated without cement (76 +/- 16.5 compared with 92 +/- 12.1, p less than 0.01). PMID- 4030830 TI - Use of the Broviac central venous catheter for intravenous antibiotic therapy in the orthopaedic patient. AB - Broviac central venous catheters were placed in twenty patients who required long term intravenous antibiotics for the treatment of osteomyelitis, septic arthritis, or an infected total joint arthroplasty. As a group, the twenty patients completed a total of 1,131 days with the catheter in place. There was only one catheter-related complication: extrusion of the Dacron cuff after removal of the catheter. Six antibiotic-related complications occurred, all of which resolved when the antibiotic was changed. No patient had sepsis related to use of the catheter, breakage of the catheter, or thrombosis. Twelve patients had part of their antibiotic treatment on an outpatient basis. PMID- 4030831 TI - Meniscal pneumatocele. A case report of spontaneous, persistent intra-articular and juxta-articular gas. PMID- 4030833 TI - Tuberculous arthritis of the elbow presenting as chronic bursitis of the olecranon. A case report. PMID- 4030832 TI - Heparin-associated thrombocytopenia with venous thrombosis. A case report. PMID- 4030834 TI - Irreducible fracture-separation of the distal ulnar epiphysis. Report of a case. PMID- 4030835 TI - Diabetic amyotrophy. A case report. PMID- 4030836 TI - Upper tibial osteotomy for osteoarthritis. PMID- 4030837 TI - "The present status of surgical treatment of Legg-Perthes disease". PMID- 4030838 TI - "Bone-mineral content in the lower limb. Relationship to cross-sectional geometry". PMID- 4030839 TI - "Total hip arthroplasty with a low-modulus porous-coated femoral component. Progress report". PMID- 4030840 TI - "Fatal pulmonary embolism following tourniquet inflation". PMID- 4030841 TI - The management of club foot. PMID- 4030842 TI - Recurrent dislocation of the patella treated by the modified Roux-Goldthwait procedure. A prospective study of forty-seven knees. AB - We studied the results in forty-seven knees in thirty-seven patients - ten male and twenty-seven female - who had recurrent dislocation of the patella and were treated by a modified Roux-Goldthwait procedure (lateral retinacular release, medial transfer of the lateral patellar tendon without advancement, plication of the medial retinaculum, and advancement of the vastus medialis). Ten of the female patients had bilateral dislocation. The results were analyzed after follow ups ranging from 3.0 to 16.3 years (average, 5.8 years). The study confirmed that a tangential radiograph of the patellofemoral joint, made with the knee in 20 degrees of flexion, is reliable in determining patellar displacement. The results were excellent in twelve knees, good in thirty-one, fair in one, and poor in three. The fair and poor ratings were due to pain caused by severe chondromalacia patellae. The patient with a fair result had had recurrent dislocations after the Roux-Goldthwait procedure due to a very lax synovial and capsular sac. Reoperation with tightening of the sac medially and laterally eliminated hypermobility of the patella in this patient and established straight patellar tracking. There was one serious complication, a large subcutaneous hematoma with necrosis of a skin flap. The patients with mild chondromalacia improved and showed no progressive patellofemoral arthritis after simple realignment, while those with severe chondromalacia were not improved by shaving, drilling, and realignment. Preliminary results indicated that a modified Maquet procedure, in addition to realignment, may be indicated for patients with severe chondromalacia. This study demonstrated that the modified Roux-Goldthwait procedure, without advancement of the tibial attachment of the patellar ligament, can stabilize the patella without increasing patellofemoral compression. The procedure does not relieve the symptoms of severe chondromalacia of the patella but realignment is the first step in treatment of any form of patellofemoral arthrosis. PMID- 4030843 TI - Arterial injuries after total hip replacement. PMID- 4030844 TI - Factors affecting the incidence of hip dislocation in cerebral palsy. AB - We have studied the natural history of spontaneous dislocation of the hip in cerebral palsy, with particular reference to the pattern of neurological involvement. In patients with bilateral hemiplegia and severe involvement of the upper limbs the incidence of dislocation was very high (59%), while in those with diplegia and little involvement of the upper limbs, only 6.5% were affected. There was no evidence of dysplasia or instability of the hip in any of the patients with unilateral hemiplegia. A strong correlation was found between the stability of the hip and the patients' ability to walk. These findings have a bearing on clinical surveillance and also on the indications for prophylactic surgery. PMID- 4030845 TI - Occlusion of the common femoral artery complicating total hip arthroplasty. AB - Vascular injuries after total hip arthroplasty are occasionally reported, but we have found only two cases of major arterial occlusion, and none at all involving the common femoral artery. We report two cases of occlusion of the common femoral artery after Charnley arthroplasties, one of which resulted in a below-knee amputation. PMID- 4030846 TI - Heparin and dihydroergotamine prophylaxis against thrombo-embolism after hip arthroplasty. AB - A prospective study involving 500 consecutive patients undergoing hip replacement was performed to find out whether a combination of heparin and dihydroergotamine was effective in preventing postoperative fatal and non-fatal emboli. Deep-vein thrombosis was demonstrated in 131 cases (26.2%), in 99 of whom thrombi were confined to the ipsilateral (operated) limb and in 13 to the contralateral limb; 19 patients developed bilateral thrombi. Nine patients (1.8%) died during the first four weeks after operation, before they were discharged from hospital; in one, major emboli were demonstrated in the right pulmonary artery. Three of the 500 patients developed non-fatal pulmonary emboli. Excessive bleeding occurred in 21 (4.2%) and in 19 of these prophylaxis was discontinued. Wound haematomas developed in 25 patients (5.0%); only six required evacuation but in none of these six did deep infection occur while in hospital; in three patients, however, the wound haematoma prolonged the stay in hospital. Thus the combination of heparin and dihydroergotamine proved an effective prophylaxis against pulmonary embolism in patients undergoing total hip replacement. The risk of bleeding complications is wholly acceptable when balanced against the advantages of the therapy. PMID- 4030847 TI - Focal lacunar resorption in the articular cartilage of femoral heads. AB - Human articular cartilage taken from 92 femoral heads at autopsy was examined macroscopically and microscopically. Fifty-two showed no changes except for occasional slight degeneration in the non-pressure areas; these changes were visible only microscopically. In the remaining 40 heads, different degrees of osteoarthrosis were seen; half the heads also showed focal lacunar resorptive lesions in the cartilage. The origin of this focal cartilage resorption is discussed and its possible association with necrosis, pannus formation and enzymatic synovial activities. We conclude that there is no evidence of a direct relationship between focal cartilage resorption and osteoarthrosis. PMID- 4030848 TI - Long-term results of Geomedic total knee replacement. AB - Seventy-one Geomedic total knee replacements were reviewed retrospectively at a maximum of eight and a half years. The prosthesis was found to be successful in its primary aim of relieving pain. However, there was an overall failure rate of 18.3%. Analysis of the results by an actuarial method allowed comparison with other prostheses. The factors involved in failure are discussed. PMID- 4030849 TI - Tibiofemoral alignment and the results of knee replacement. AB - We examine the hypothesis that a knee replacement is most likely to survive successfully if it is stable with a coronal tibiofemoral angle close to 7 degrees of valgus, the accepted normal. The records of 428 knee replacements followed up for one to nine years were analysed. The highest success rate was indeed found in those so aligned at operation and such knees were most likely to remain stable. Nevertheless, half of the failures occurred in knees correctly aligned at operation and two-fifths in knees which had remained stable in this alignment; many failures must have been caused by factors other than malalignment. Some knees, well aligned at operation, deteriorated into severely varus or valgus positions; their failure rate was significantly higher than that for knees which remained normally aligned and higher also than for knees severely varus or valgus from operation onwards. Malalignment, in itself, may not be the most important cause of failure, though it probably does compound failure from other causes. PMID- 4030850 TI - Autogenous patella as replacement for a resected femoral or tibial condyle. A report on 19 cases. AB - The size and shape of the patella make it suitable for the partial replacement of a femoral or tibial condyle resected for tumour, or destroyed by trauma. It can provide a good articular surface and may give satisfactory knee function. Nineteen cases of patellar grafts are presented, with follow-up from two to nine years. Good consolidation of the graft and fair stability of the joint were obtained; the range of movement was 90 degrees or more in 79% of cases. In contrast with an allograft of a femoral or tibial condyle, the technique described does not need an allograft bank, has a lower risk of infection, and allows better and quicker consolidation and revascularisation of the grafts, as well as a better range of movement at the knee, probably because of the lack of fibrosis from immunological reaction. Merle d'Aubigne's technique, using a patellar graft with a vascular muscle pedicle, is useful only for some cases, requires a longer period of immobilisation and weakens the extensor apparatus. Our series shows that consolidation and revascularisation of a patellar graft can occur in the absence of a pedicle. PMID- 4030851 TI - Torsion of localised pigmented villonodular synovitis of the knee. AB - Torsion and subsequent ischaemia is a well-recognised cause of symptoms and morbidity in general surgery. We present three cases of solitary pigmented villonodular tumours of the knee which were found to have undergone torsion. We believe these to be the first intra-articular tumours in which torsion has been reported. PMID- 4030852 TI - Congenital absence of the anterior cruciate ligament. A common component of knee dysplasia. AB - The clinical and radiological features of 12 knees (10 patients) with congenital absence of the anterior cruciate ligament are presented. The high frequency of this condition in association with other more easily recognised congenital abnormalities of the knee is discussed. It is concluded that congenital absence of the anterior cruciate ligament is more common than generally suspected and is associated with other developmental abnormalities of both bone and soft tissue in the lower limb, particularly around the knee joint. PMID- 4030853 TI - The treatment of 143 tibial shaft fractures by Ender's nailing and early weight bearing. AB - A prospective study of 141 patients with 143 tibial shaft fractures has been carried out; 102 fractures were closed and 41 open. All the patients were treated by Ender's nailing and early weight-bearing. The average healing time was 15.2 weeks. There were no cases of bone infection and complications were minimal, the commonest being slight malalignment. Using this method, rapid restoration of bone continuity was achieved, combined with almost normal limb function during treatment. PMID- 4030854 TI - Congenital deficiency of the tibia. AB - The late results of treatment of 24 legs in 21 children with congenital deficiency of the tibia are presented. A new classification is proposed which correlates well with recommendations for treatment and with the final functional result. Three types of deficiency were recognised: Type I, total absence of the tibia; Type II, distal absence; Type III, distal deficiency with tibiofibular diastasis. The early radiographic appearances, the functional status of the quadriceps and the severity of flexion contracture of the knee were important factors in the selection of the operations likely to give the best function. PMID- 4030855 TI - A repair operation for recurrent dislocation of peroneal tendons. AB - A lesion similar to that described by Bankart in recurrent dislocation of the shoulder was seen in seven patients with recurrent dislocation of the peroneal tendons. Detachment of the periosteum had resulted in the formation of a false pouch on the surface of the lower end of the fibula; into this pouch the peroneal tendons could easily dislocate. Reattachment of the periosteum to drill holes in the fibula prevented dislocation, and this anatomical method of repair is described. This lesion is one of the causes of recurrent dislocation of the peroneal tendons. PMID- 4030856 TI - The results of early posterior release in resistant club feet. A long-term review. AB - Seventy resistant club feet in 46 patients were treated within the first six months of life by posterior release as an incident in continuing conservative care and were later assessed at an average age of 15 years. Assessment was made upon strict clinical criteria, including appearance, function and degree of pain during activity; the results were excellent in 22 feet, good in 19, and poor in 29. We also studied the correlation between the radiographs and the final outcome. From these data we propose certain indications for the timing and technique of this type of management, and also discuss the relative merits of this approach compared with more conventional radical release operations. PMID- 4030857 TI - Stature and its components in adolescent idiopathic scoliosis. Cephalo-caudal disproportion in the trunk of girls. AB - Stature and its components were examined in 143 girls aged 11 to 15 years with adolescent idiopathic scoliosis. Correction was made for loss of height due to the lateral spinal curvature, and the findings were compared with those from 202 healthy girls of similar age. Using three components of stature (suprapelvic, pelvic and subischial heights) we were able to show that the relatively greater stature of girls with adolescent idiopathic scoliosis was due to changes in the pelvis and lower limbs but not significantly in the spine. Suprapelvic height was reduced relative to subischial height; this probably represents the growth pattern of predominantly ectomorphic individuals, reflecting the physique of many of these girls. Pelvic height was disproportionately increased, and this is considered to be a true rather than an apparent difference. Cephalocaudal disproportion involving two segments suggests a common mechanism of causation which is unlikely to be secondary to the scoliosis. These physical features may in some way be associated with a predisposition to progression of the scoliosis. PMID- 4030858 TI - Costovertebral anomalies in osteogenesis imperfecta. AB - Study of 16 patients with Type III osteogenesis imperfecta showed marked elongation of the pedicles of the vertebrae in all cases, a deformity which was not seen in other types of the disease. Posterior rib angulation was also noted in Type III disease. These features have proved useful in suggesting the diagnosis of osteogenesis imperfecta even before long bones have fractured and in categorizing patients with osteogenesis imperfecta into the correct type for prognostic purposes. PMID- 4030859 TI - Pyogenic infection of the sacro-iliac joint. A report of 11 cases. AB - We report 11 patients who, over a five-year period, were treated for pyogenic infection of the sacro-iliac joint. This condition is uncommon and difficult to assess, so that diagnosis is liable to be delayed and morbidity increased. Skeletal scintigraphy, with perfusion phase imaging, is usually positive in early lesions and prompt antibiotic treatment reduces complications. PMID- 4030860 TI - Operations for cervical spondylotic myelopathy. A comparison of the results of anterior and posterior procedures. AB - Over the past 19 years we have operated on 269 patients with myelopathy associated with cervical spondylosis. We report our results in 191 cases which we have followed up for 1 to 12 years (average 31 months). The clinical state before and after operation was recorded using the criteria of the Japanese Orthopaedic Association. Posterior operations gave better results than anterior for the more advanced myelopathies such as transverse lesions, the Brown-Sequard syndrome and the motor syndromes, but the brachialgia and cord syndrome and the central cord syndrome were satisfactorily treated by anterior operations. Of the three anterior and three posterior techniques used, no single one showed an overall superiority. A short duration of symptoms before operation was associated with better results, but these were not influenced by the age of the patients. PMID- 4030861 TI - The transverse posterior approach to the neck. AB - Traditional posterior approaches to the neck use a vertical craniocaudal incision which often leaves an unsightly scar. An incision along Langer's transverse lines of tension divides only the cross-fibres of the dermis and we have found the results of this approach encouraging: wound healing was uncomplicated and the cosmetic appearance excellent. PMID- 4030862 TI - Major ruptures of the rotator cuff. The results of surgical repair in 89 patients. AB - Major ruptures of the rotator cuff were repaired in 89 patients over a six-year period, using an approach through the split deltoid muscle and the bed of the excised outer centimetre of the clavicle. Review of these patients showed that poor results were associated with larger cuff defects, with more pre-operative steroid injections and with pre-operative weakness of the deltoid muscle. A randomised prospective study showed that repair followed by splinting in abduction gave no better results than repair followed by resting the arm at the side. Excision of the coraco-acromial ligament was associated with worse results than leaving its divided halves in situ. Follow-up showed that the results continued to improve for two years after operation; their quality was maintained in patients less than 60 years old, but in those over 60 there was deterioration with time. PMID- 4030863 TI - The effect of posture on the lumbar spine. AB - A series of experiments showing how posture affects the lumbar spine is reviewed. Postures which flatten (that is, flex) the lumbar spine are compared with those that preserve the lumbar lordosis. Our review shows that flexed postures have several advantages: flexion improves the transport of metabolites in the intervertebral discs, reduces the stresses on the apophyseal joints and on the posterior half of the annulus fibrosus, and gives the spine a high compressive strength. Flexion also has disadvantages: it increases the stress on the anterior annulus and increases the hydrostatic pressure in the nucleus pulposus at low load levels. The disadvantages are not of much significance and we conclude that it is mechanically and nutritionally advantageous to flatten the lumbar spine when sitting and when lifting heavy weights. PMID- 4030864 TI - Patterns of injury to the terminal branches of the brachial plexus. The place for early exploration. AB - Non-operative management has frequently been adopted for closed injuries of the infraclavicular brachial plexus and its branches in the belief that spontaneous recovery is likely to occur, and surgical exploration is performed only if recovery has not occurred in the expected time. This paper correlates the clinical and electrophysiological features with the operative findings in six patients with such injuries. The axillary nerve was ruptured in all six patients, the musculocutaneous nerve in two and the radial nerve in two. When the muscles supplied by a branch of the plexus were denervated, the differentiation between rupture of that branch and a lesion in continuity could only be made by surgical exploration, which should be performed as soon as other injuries permit. PMID- 4030865 TI - Rehabilitation of conversion paralysis. AB - Three patients referred for rehabilitation of brachial plexus lesions and two referred with leg weakness associated with sciatica were found to have conversion paralysis. The diagnosis was made by demonstrating normal motor nerve conduction to the clinically weak muscles. The weakness was treated by intensive physical rehabilitation with complete and sustained recovery in all cases. PMID- 4030866 TI - Injury to the medial humeral condyle in a child reviewed after 18 years. Report of a case. PMID- 4030867 TI - Pectoralis major transfer for paralysis of elbow flexion in children. AB - Seven pectoralis major transfers in children suffering from bilateral paralysis of elbow flexion due to arthrogryposis or to trauma are reported. A technique is described in which the muscle is mobilised from the clavicle to allow the tendon of insertion to be attached to the biceps tendon at the elbow. The biceps tendon was found to be present and could be mobilised forwards in all the arthrogrypotic elbows. Subjectively, the results were considered by patients or parents to be very good in six cases and fair in one. Elbow flexion power against gravity and against some resistance was achieved in all patients except one. The overall function was very good in one elbow, good in two, fair in three and poor in only one. The merits of the various procedures described for the restoration of elbow flexion in arthrogryposis are discussed. It is concluded that total pectoralis major transfer by the method described here has given the best results. PMID- 4030868 TI - Histological response to carbon fibre. AB - The soft tissue response to carbon fibre was studied histologically one and a half years after being used to reconstruct the lateral collateral ligament of the human knee. A remarkably consistent pattern was seen in the induced ligament. The basic pattern was a "composite unit", consisting of a core of carbon fibre enveloped in a concentric manner by coherent layers of fibroblasts and collagen fibres. This new structure seemed to have been induced by continuous irritation caused by the physical structure of the carbon fibres; it is unlikely ever to acquire the structure of a natural ligament. However, it is biologically compatible and is biomechanically sufficient as long as the entire tow of carbon fibres is preserved. PMID- 4030869 TI - The influence of induced micromovement upon the healing of experimental tibial fractures. AB - Although it has been well established that fracture healing is influenced by the mechanical environment, the optimal parameters have not yet been established. In two groups of sheep an experimental tibial diaphysial fracture was created, and stabilised using external skeletal fixation. In one group rigid fixation was maintained throughout fracture healing; in the other group controlled axial micromovement, with a loading regime known to be osteogenic in intact bones, was applied for a short period daily. A significant improvement in healing was associated with the application of controlled micromovement. Data from these experiments provide the basis for improving the conditions for fracture healing and may assist in the prevention of delayed union. PMID- 4030870 TI - The response of human tissues to carbon reinforced epoxy resin. AB - The tissue surrounding carbon fibre reinforced epoxy resin plates applied to forearm and tibial fractures was biopsied in 32 patients at the time the plates were removed. The reaction was minimal and was compared with that in a control group of 16 similar patients in whom stainless steel plates were used. No significant histological differences were found. A series of experiments on rats, in which the histology was studied from 2 to 78 weeks, also showed that there was very little reaction to carbon fibre reinforced plastic. PMID- 4030871 TI - Magnetic resonance imaging in orthopaedic surgery. A glimpse into the future. AB - Magnetic resonance images (MRI) were obtained of 10 healthy volunteers and 70 patients suffering from various orthopaedic disorders. Selected images of soft tissue, joint, bone and spinal abnormalities are presented and their interpretation is described. Although we have been using MRI for only a very short time, it is already possible to see its advantages: it provides good images of soft-tissues, detailed pictures of bone marrow, and excellent visualisation of the spine and spinal cord. The decision-making process in surgical procedures will in the future be influenced by this technique. PMID- 4030872 TI - Valve replacement in the elderly: a long term appraisal. AB - From July 1972 through July 1983, 360 consecutive patients 70 years of age and older (mean age 74.1; range 70-88 years) underwent 362 valve replacement procedures. There were 122 isolated aortic valve replacements (33.7%; Group I); 70 isolated mitral valve replacements (19.3%; Group II); and 170 patients had combined procedures (47.0%; Group III), which included the replacement of at least one valve. Eighteen patients (5.0%) had previous cardiac surgery. Thirty two patients (8.8%) were operated as emergencies. Three hundred and thirty-two (86.5%) of all valves implanted were porcine heterografts. Pre-operatively, over one-half (53.6%) of the patients were in New York Heart Association Functional Class IV. The overall hospital mortality was 13.8% (50 patients). The aortic valve mortality was 11.5%, the mitral valve mortality was 15.7%, and the combined procedures 14.7%. The follow-up period for hospital survivors (312 patients) extended from 2 weeks to 127.2 months, with a mean of 38.7 months or a total of 1,006 patient-years. The long term survival computed up to six years shows a 65 +/- 3.8% (standard error of the mean) for the entire group. The aortic valve group survival was 71 +/- 5.6%; the mitral valve group 60 +/- 8.2%; and the combined procedures group was 64 +/- 5.3%. Postoperative functional improvement was significant with 71.8% of the survivors in Class I and 19.6% in Class II. Based on these results, advanced age can no longer be considered a deterrant to cardiac surgery. The porcine heterograft appears to be the valve substitute of choice for this age group.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4030873 TI - Advantages of superior approach for mitral valve surgery. AB - Technical factors in mitral valve surgery (MVS) which may influence neurological complications, trauma to the left atrium and formation of atrial mural thrombi have not previously been described in detail. We have reviewed the records of 146 patients (pts) undergoing MVS through the superior approach between January 1974 and May 1981. The series consisted of 97 females and 49 males with a mean age of 57 +/- 18 years. All but 4 pts were in New York Heart Association functional class III or IV. Twenty-five pts underwent open mitral commissurotomy, 116 had valve replacement and 5 had annuloplasty. Concomitant procedures were coronary bypass in 47, aortic valve replacement in 18 and resection of left ventricular aneurysm in 3. Left atrial thrombi were removed in 21 pts. Thirteen pts (9%) died postoperatively. The causes of death were left ventricular failure in 7, arrhythmia in 4 and atrio-ventricular disruption in 2. Two of these pts also had cerebral dysfunction. Autopsy examination in 8 pts failed to reveal formation of fresh left atrial septal or posterior mural thrombus. Postoperative complications included transient neurologic injury presumed to be due to air embolus in 3 and postoperative bleeding from atrial suture line in one. The mean follow-up for the survivors has been 30 months. There have been 16 (12%) late deaths from 1 to 72 months (mean 15). Autopsy examination of 4 pts and surgical exploration in one other pt which failed to reveal organized left atrial mural thrombus. Only one late death was related to prosthetic thrombosis. This occurred following cessation of anticoagulations.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4030874 TI - Aortic valvotomy in the treatment of congenital aortic stenosis. AB - Forty patients aged 1.5-23 (mean 11) years underwent open aortic valvotomy for congenital aortic stenosis. Mean preoperative peak aortic gradient for the group was 88 (SD +/- 24) mmHg. Follow-up data was available on all patients for a total of 269 patient-years (means 6.6 year). There was no early mortality, and only one (2.5%) late death. During the follow-up period 3 patients (7.5%) required aortic valve replacement. Actuarial survival curves predict a 7 year survival of 95.7 (SE +/- 8.4%) for all patients, and a freedom from reoperation rate at 6 years of 8.7 (SE +/- 9.3)%. Symptomatic results in the survivors were excellent (97.5% NYHA Class I). Data from this series compares favourably with the literature which is reviewed for a total of 1136 patients undergoing open aortic valvotomy. PMID- 4030875 TI - Surgical management of infected median sternotomy: closed irrigation vs. muscle flaps. AB - Mediastinitis remains a serious complication of median sternotomy which requires prompt and aggressive surgical management. Debridement and closed irrigation has been the conventional mode of treatment. Failure to respond results in open drainage and delayed healing with its associated increased morbidity and mortality. Secondary closure with rectus muscle flaps has been a marked advance in the treatment of these patients. In an attempt to define guidelines for the treatment of mediastinitis complicating median sternotomy, a retrospective review of 2,400 cardiac surgical cases at St. Vincent's Hospital from 1977 through 1982 was performed. There were 25 cases (1%) of mediastinitis. Debridement and closed irrigation was successful in 16 patients (64%) with an average postoperative hospital stay of 19 days. Failure resulted in open drainage in 2 patients (8%) with an average hospital stay of 66 days and debridement and secondary closure by rectus muscle flaps in 7 patients (28%) with an average hospital stay of 28 days. There were no deaths in the entire series. Failure to respond to closed irrigation was not due to delay in diagnosis. The length of time between operation and the first sign of sternal dehiscence did not vary significantly. Sternal dissolution, the presence of anaerobic organisms, large volumes of purulent and necrotic material, however, were responsible for continued mediastinitis and further sternal dehiscence. Open irrigation and delayed closure with muscle flaps should be reserved for these patients and appears to decrease significantly morbidity and length of hospital stay. Surgical debridement and closed irrigation, however, remains the primary method of treatment of the less virulent forms of mediastinitis following median sternotomy. PMID- 4030876 TI - A comparison of blood and Fluosol-DA for cardiopulmonary bypass. AB - Fluosol-DA was compared to blood as a pump prime for total cardiopulmonary bypass in the pig animal model. Nineteen pigs weighing between 14 and 22 kg were studied, nine with blood and ten with Fluosol. Metabolic and hemodynamic measurements were determined before, during and after 60 minute bypass to establish the adequacy of Fluosol to sustain perfusion as compared to blood. The measurements and subsequent calculations included blood gases, arterial and mixed venous oxygen content, oxygen extraction and consumption, cardiac output, systemic and pulmonary vascular resistance and arterial, venous, pulmonary artery and left atrial pressures. The result showed a significant decrease in hematocrit during bypass in the Fluosol group as compared to blood perfusion (20 vs. 30%). While the arterial oxygen content fell from control levels with Fluosol during bypass, in the blood prime group, oxygen content remained at pre-control levels. Whole body oxygen consumption decreased during bypass, in both groups equally, but this decrease did not lead to acidosis and was stable during recovery. Oxygen and carbon dioxide transport were adequately maintained during bypass in both Fluosol and blood groups. Systemic pressures remained stable during bypass and were lower, but stable, during recovery. Pulmonary vascular resistance was elevated in both groups during recovery which probably explains a concomitantly decreased cardiac output. There was a 40% mortality in both experimental groups secondary to postpump pulmonary hypertension. It is concluded that Fluosol is a satisfactory oxygen carrying agent to be used instead of blood during cardiopulmonary bypass, and in the pig model both blood and Fluosol were associated with a high incidence of pulmonary hypertension. PMID- 4030877 TI - Experimental cardioplasty using the latissimus dorsi muscle flap. AB - This study was undertaken to examine the possibility of using the latissimus dorsi muscular flap, divided in two parts thus covering the surfaces of the heart, and inserting it into the thoracic cavity by means of a segmental resection of the second rib. After cadaver case studies, 15 operations were performed on 5 Beagle dogs. The first group of 5 operations consisted of a latissimus dorsi flap graft over the heart. The second group and third group of operations (3 and 6 months later) consisted of reoperating for muscular and cardiac biopsies and electrical stimulation tests on the heart-muscle complex. The latissimus dorsi flap provided a sizable mass of contractile tissue. The haemodynamic studies showed no compressive or constrictive phenomenon of the muscle on the heart and revealed the preservation of an appropriate cardiac output for short intervals of time (2 hours), through phasic electrostimulation of the flap. The histopathological studies showed conserved muscular structure. The technical feasibility, histological adaptability and electrophysiological properties of this muscular flap makes it appropriate to develop a functional stimulation programme and perhaps adequate for the treatment of dysplasic, ischemic, tumoral and other acquired or congenital myocardial diseases. PMID- 4030878 TI - Six year experience with expanded polytetrafluoroethylene arterial grafts for limb salvage. AB - We have used 822 polytetrafluoroethylene (PTFE) grafts in arterial reconstructions for limb salvage over the last 6 years at Montefiore Medical Center-Albert Einstein College of Medicine, Four hundred and twenty-seven femoropopliteal reconstructions with PTFE had a 6 year cumulative life table patency rate of 55% with follow-up of 76 grafts for more than 3 years and 28 grafts for more than 4 years. Seventy-nine bypasses to the isolated popliteal segment had a 6 year cumulative patency rate of 72%. There were 207 bypasses performed to the tibial, peroneal or dorsalis pedis arteries. Life table patency rates were 55% at 1 year, 40% at 2 years and 37% at 4 years. Ninety-two PTFE femorofemoral and 62 axillofemoral bypasses had 5 1/2 year cumulative life table patency rates of 83% and 75%, respectively. Axillopopliteal PTFE bypasses can salvage otherwise doomed limbs. Thirty-four such grafts had 74% 1 year and 45% 5 year patency rates. The overall infection rate in all 822 PTFE grafts was only 0.5%. Thus, PTFE is a promising vascular prosthetic material which facilitates otherwise difficult or impossible limb salvage procedures. PMID- 4030879 TI - Methods of suppression of myonephropathic metabolic syndrome. AB - Acute arterial occlusion of the extremities may result in severe and complex metabolic derangements. In order to investigate therapeutic means of controlling such metabolic derangements, 19 adult mongrel dogs weighing between 7 and 15 kg underwent acute arterial occlusion by cross-clamping the infrarenal aorta. Clamping was released after 48 hours. The experimental animals were divided into three groups: an untreated group, a THAM group, and a perfusion group. Biochemical and electrolyte analyses were measured before and 1 hour after occlusion, and 1, 3, 12, 24, and 48 hours after the release of occlusion. The SGOT, creatinine, CPK, and aldolase levels rose after release of the occlusion and were significantly higher in the untreated group than in the THAM and perfusion groups. Among these enzymatic changes, the CPK level showed the largest increase. The serum potassium levels remained almost at preocclusion levels after release of the occlusion. It was concluded that the intravenous administration of THAM and peripheral washing were effective against untoward metabolic changes occurring in the ischemic extremities. PMID- 4030880 TI - Arterial thrombosis and embolism in malignancy. AB - In most reviews of arterial embolism or thrombosis the source of emboli or the cause of thrombosis can reasonably be established in over 90% of patients. Still about 10% remain without demonstrable cardiac or intraarterial sources. Although hypercoagulability induced by malignancy has been alluded to as a cause of unexplained intravascular thrombosis reports of arterial thromboembolism with such association are rare. Seven patients with unequivocal thromboembolism are presented. Two distinct clinical patterns are observed, one with in situ thrombosis of small arteries and the other with occlusion of large arteries causing limb ischemia or fatal organ infarction. The various pathogenetic mechanisms of arterial thrombosis or embolism in malignancy include sustained spasm of arteries, precipitation of cryoglobulins or other abnormal proteins in small arteries, direct tumor invasion of arteries, fragmentation and embolization of intracardiac or intraarterial metastases and spontaneous arterial thrombosis due to hypercoagulability. The hypercoagulable state can be recognized by the observation of shortened bleeding and clotting times, partial thromboplastin and prothrombin times, elevation of coagulation factors, platelets and yield stress index and resistance to anticoagulation. Patients presenting with arterial thromboembolic events with out demonstrable source should be investigated for malignancy. Conversely patients with malignancy should be searched for evidence of hypercoagulability in an attempt to prevent arterial thromboembolic complications. PMID- 4030881 TI - Surgical treatment for dissecting aneurysm of the aorta using a double ringed graft. AB - Since 1978 we have been using a new double ringed graft for the treatment for dissecting aneurysm of the aorta. This prosthesis is a segment of a woven Dacron graft with two stainless steel rings, fixed and sutured in place, 10 or 12 mm apart, at each end of the graft. The operative procedure is as follows: the graft is tied into the true lumen of the dissected aorta; tape is ligated around the aorta and fixed between the two rings; and suturing of the aortic layers is done over the inserted graft. This technique has been applied in 11 cases of dissecting aneurysm. Eight patients survived, and 3 died soon after surgery due to complications. The safety of this method was ascertained by experimental and pathohistological studies. PMID- 4030882 TI - Thoracic aortic aneurysm secondary to giant cell arteritis: a reappraisal of etiology, treatment and possible prevention. AB - 43 patients with thoracic aortic aneurysms (TAA) were treated over a ten-year period at our hospital. Five (11.6%) had giant cell arteritis (GCA). Although many types of arteritis have been reported, all have pathologic features of elastic degeneration and granulomatous inflammation and may share a common underlying etiology. TAA secondary to arteritis frequently involves the ascending aorta, leading to aortic root dilatation and valvular insufficiency. Three of five of our patients had these findings and had successful surgical repair by combined aortic valve and ascending aorta replacement. Patients with TAA secondary to arteritis should be investigated further, looking for evidence of additional arterial disease. Because corticosteroids have prevented the progression of other types of arteritis, further investigation of their efficacy in the treatment of giant cell arteritis may be warranted. PMID- 4030883 TI - Fibromuscular dysplasia in the extremities. AB - Four patients had fibromuscular dysplasia of the extremities involving the brachial, deep femoral, popliteal, anterior and posterior tibial and peroneal arteries. One of them demonstrated a string-of-beads appearance in the superficial veins of the arm and this was pathologically confirmed as fibromuscular dysplasia. We believe this is the first report of this disease affecting the peripheral arteries and the superficial veins of the extremities. The sympathetic system seems to be related to the development of fibromuscular dysplasia. PMID- 4030884 TI - An evaluation of resting arterial ischemia models in the rat hind limb. AB - Techniques for using the rat hind limb as a model of pure arterial ischemia at rest have not been well defined. Because the rat has no profunda femoral artery, numerous collateral pathways exist to the hind limb, and femoral artery ligation is not an effective method of inducing arterial ischemia. After several anatomic studies, a two stage operation to produce arterial ischemia in the left hind limb was devised. The first stage involved surgical interruption of collateral and re entrant vessels, and the second stage involved femoral artery ligation. Using Xenon 133 clearance as an estimate of blood flow, reduction in flow to 14, 24, and 37% of the simultaneously measured value in the right hind limb was obtained at 2 hours, 2 days, and 5 days post ligation. Oxygen extraction in the left hind limb doubled both at 2 hours and at 2 days post ligation. Histological evaluation of the anterior compartment musculature after 5 days demonstrated loss of nuclei, degenerating contractile elements, edema, and inflammatory infiltrate. Evaluation of rats that had undergone isolated femoral artery ligation showed a 66% reduction in flow 2 hours after ligation, but no reduction in flow at 5 days, no increase in oxygen extraction, and only nuclear changes on histological exam at five days. PMID- 4030885 TI - Renal artery graft-to-duodenum fistula: unusual presentation of a recurrent flank abscess. AB - Perhaps the most devastating complication of a prosthetic vascular graft is the formation of an aortoenteric fistula. Most reports have dealt with fistulas between the aortic graft and the duodenum, although any revascularized vessel with prosthetic material can be the site of an enteric fistula. We report an unusual case in which a renal artery previously revascularized with a silk prosthetic graft developed a fistula to the duodenum 16 years later. Whether the prosthetic graft is in the aortic position or to a visceral vessel, when a fistula develops the only acceptable treatment is complete removal of the graft and revascularization with autogenous tissues, if necessary. PMID- 4030886 TI - Incarcerated femoral hernia after an aortofemoral bypass graft. PMID- 4030887 TI - A multipurpose grasping forceps for retrieval of an embolized catheter fragment. AB - Transjugular removal of an embolized catheter fragment from the right atrium of a 6-month-old infant was successfully performed using a multipurpose grasping forceps. All procedures for the retrieval were completed in only 10 minutes without complications or difficulty. PMID- 4030888 TI - XVII World Congress of the International Society for Cardiovascular Surgery. August 25-30, 1985, Monte Carlo, Monaco. Abstracts. PMID- 4030889 TI - The presence of two skeletal muscle alpha-actinins correlates with troponin tropomyosin expression and Z-line width. AB - Two species of alpha-actinin from rabbit fast skeletal muscles were identified with a monospecific antisera. Designated alpha-actinin1f and alpha-actinin2f, their distribution in muscles does not correlate with histochemically defined fast fiber type. Rather, the presence of each correlates with Z-line width and with the expression of different thin filament Ca2+-regulatory complexes. alpha Actinin1f is expressed with troponin T 1f-alpha beta tropomyosin, and alpha actinin2f with troponin T 2f-alpha 2 tropomyosin. CNBr peptide maps show that the fast alpha-actinin species differ in primary structure. In contrast, the slow alpha-actinin is indistinguishable from alpha-actinin1f. Further evidence for the similarity of alpha-actinin1f and slow alpha-actinin comes from electron microscopic studies which show that fibers that express these species exhibit thick Z-lines. So, unlike other contractile proteins, the multiple forms of alpha actinin do not reflect the distinction between fast- and slow-twitch muscles. PMID- 4030890 TI - A novel giant secretion polypeptide in Chironomus salivary glands: implications for another Balbiani ring gene. AB - Chironomus salivary glands contain a family of high Mr (approximately 1,000 X 10(3)) secretion polypeptides thought to consist of three components: sp-Ia, sp Ib, and sp-Ic. The use of a new extraction protocol revealed a novel high Mr component, sp-Id. Results of a survey of individual salivary glands indicated that sp-Id was widespread in more than a dozen strains of C. tentans and C. pallidivittatus. Sp-Id was phosphorylated at Ser residues, and a comparison of cyanogen bromide and tryptic peptide maps of 32P-labeled polypeptides suggested that sp-Ia, sp-Ib, and sp-Id are comprised of similar but nonidentical tandemly repeated amino acid sequences. We concluded that sp-Id is encoded by an mRNA whose size and nucleotide sequence organization are similar to Balbiani ring (BR) mRNAs that code for the other sp-I components. Furthermore, parallel repression of sp-Ib and sp-Id synthesis by galactose led us to hypothesize that both of their genes exist within Balbiani ring 2. PMID- 4030892 TI - Metastatic potential of B16 melanoma cells after in vitro selection for organ specific adherence. AB - Heterogeneous primary tumors contain subpopulations of cells that differ in ability to metastasize to specific host organs. We have used cryostat sections of host organs to select for metastatic variants of B16 melanoma cells with increased adhesion to specific syngeneic tissues. By repeating the selection procedure with lung tissue, a subpopulation of cells was isolated that demonstrated a specific increase in binding to cryostat sections of mouse lung. This altered binding was reflected by a sixfold increase in the frequency of lung metastasis 21 d after tail vein injection of the tumor cells. In contrast, B16 melanoma cells selected on cryostat sections of mouse brain showed no increase in adhesion to brain or lung tissue and the metastatic pattern in vivo was not significantly different compared with the parent cell line. When cells selected for increased adhesion to cryostat sections of lung were further examined in vitro, they showed altered morphology and increased motility but no change in growth rate. These results demonstrate that alterations in the adhesive interactions between metastatic tumor cells and a specific host tissue can directly affect the frequency of metastasis to that tissue in vivo. PMID- 4030891 TI - Platelet-derived growth factor and heparin-like glycosaminoglycans regulate thrombospondin synthesis and deposition in the matrix by smooth muscle cells. AB - Platelet-derived growth factor (PDGF), a smooth muscle cell (SMC) mitogen, and heparin-like glycosaminoglycans, known inhibitors of SMC growth and migration, were found to regulate thrombospondin synthesis and matrix deposition by cultured rat aortic SMC. The synthesis and distribution of thrombospondin was examined in growth-arrested SMCs, in PDGF-stimulated SMCs, and in heparin-treated SMCs using metabolic labeling and immunofluorescence techniques. Thrombospondin synthesis in response to purified PDGF occurred within 1 h after addition of growth factor to growth-arrested SMCs, peaked at 2 h, and returned to baseline levels by 5 h. The induction of synthesis of thrombospondin by PDGF was dose dependent, with a maximal effect observed at 2.5 ng/ml. Actinomycin D (2 micrograms/ml) inhibited thrombospondin induction by PDGF, suggesting a requirement for new RNA synthesis. In the presence of heparin and related polyanions, the incorporation of thrombospondin into the SMC extracellular matrix was markedly reduced. This effect was dose dependent with a maximal effect observed at a heparin concentration of 1 microgram/ml. Heparin did not affect the ability of SMCs to synthesize thrombospondin in response to PDGF. We interpret these data to suggest a role for thrombospondin in the SMC proliferative response to PDGF and in the regulation of SMC growth and migration by glycosaminoglycans. PMID- 4030893 TI - Properties of the kinetochore in vitro. I. Microtubule nucleation and tubulin binding. AB - We have isolated chromosomes from Chinese hamster ovary cells arrested in mitosis with vinblastine and examined the interactions of their kinetochores with purified tubulin in vitro. The kinetochores nucleate microtubule (MT) growth with complex kinetics. After an initial lag phase, MTs are continuously nucleated with both plus and minus ends distally localized. This mixed polarity seems inconsistent with the formation of an ordered, homopolar kinetochore fiber in vivo. As isolated from vinblastine-arrested cells, kinetochores contain no bound tubulin. The kinetochores of chromosomes isolated from colcemid-arrested cells or of chromosomes incubated with tubulin in vitro are brightly stained after anti tubulin immunofluorescence. This bound tubulin is probably not in the form of MTs. It is localized to the corona region by immunoelectron microscopy, where it may play a role in MT nucleation in vitro. PMID- 4030894 TI - Properties of the kinetochore in vitro. II. Microtubule capture and ATP-dependent translocation. AB - We have studied the interaction of preformed microtubules (MTs) with the kinetochores of isolated chromosomes. This reaction, which we call MT capture, results in MTs becoming tightly bound to the kinetochore, with their ends capped against depolymerization. These observations, combined with MT dynamic instability, suggest a model for spindle morphogenesis. In addition, ATP appears to mobilize dynamic processes at captured MT ends. We used biotin-labeled MT seeds to follow assembly dynamics at the kinetochore. In the presence of ATP and unlabeled tubulin, labeled MT segments translocate away from the kinetochore by polymerization of subunits at the attached end. We have termed this reaction proximal assembly. Further studies demonstrated that translocation could be uncoupled from MT assembly. We suggest that the kinetochore contains an ATPase activity that walks along the MT lattice toward the plus end. This activity may be responsible for the movement of chromosomes away from the pole in prometaphase. PMID- 4030896 TI - Metabolic cooperation between vascular endothelial cells and smooth muscle cells in co-culture: changes in low density lipoprotein metabolism. AB - A microcarrier co-culture system for aortic endothelial cells and smooth muscle cells (SMCs) was developed as a model for metabolic interactions between cells of the vessel wall. Low density lipoprotein (LDL) metabolism in SMCs was significantly influenced by co-culture with endothelium. The numbers of high affinity receptors for LDL was increased more than twofold (range, 2.1-5.6), with concomitant increases in LDL receptor-mediated endocytosis and degradation. These effects reached a plateau at an endothelial cell/SMC ratio of 1. Kinetic analysis of the endocytic pathway for LDL in SMCs indicated that, in co-culture with endothelium, there was no alteration in the binding affinity of LDL to its receptors but that the internalization rate constant declined and the rate constant for degradation increased. This analysis suggested that the formation and migration of endocytic vesicles was the rate-limiting step of enhanced LDL metabolism under co-culture conditions. Two mechanisms by which endothelial cells influenced smooth muscle LDL metabolism were identified. First, mitogen(s) derived from endothelial cells stimulated entry of SMCs into the growth cycle, and the changes in LDL metabolism occurred as a consequence of G1-S transition. Second, SMC lipoprotein metabolism was stimulated in the absence of mitogens by a low molecular weight (less than 3,500) factor or factors. Co-culture was a required condition for the latter effect, suggesting that the mediator(s) may be unstable or that cell-cell communication was necessary for expression. These results (a) demonstrate that vascular cell interactions can modify LDL metabolism in SMCs, (b) provide some insights into the mechanisms responsible, and (c) identify co-culture as an experimental approach appropriate to certain aspects of vascular cell biology. PMID- 4030895 TI - Lithium ion inhibits nerve growth factor-induced neurite outgrowth and phosphorylation of nerve growth factor-modulated microtubule-associated proteins. AB - LiCl (2.5-20 mM) reversibly suppressed nerve growth factor (NGF)-induced neurite outgrowth by cultured rat PC 12 pheochromocytoma cells. Similar concentrations of LiCl also reversibly blocked NGF-dependent regeneration of neurites by PC12 cells that had been primed by long-term pre-exposure to NGF and by cultured newborn mouse sympathetic neurons. In contrast, transcription-dependent responses of PC12 cells to NGF such as priming and induction of the NGF-inducible large external glycoprotein, occurred despite the presence of Li+. SDS PAGE analysis of total cellular phosphoproteins (labeled by 2-h exposure to 32P-orthophosphate) from neurite-bearing primed PC12 cells revealed that Li+ reversibly inhibited the phosphorylation of a band of Mr 64,000 that was barely detectable in NGF untreated PC12 cells. However, Li+ did not appear to affect the labeling of other phosphoproteins in either NGF-primed or untreated PC12 cultures, nor did it affect the rapid increase in phosphorylation of several proteins that occurs when NGF is first added to unprimed cultures. Several criteria indicated that the NGF inducible phosphoprotein of Mr 64,000 is a microtubule-associated protein (MAP). Of the NGF-inducible phosphorylated MAPs that have been detected in PC12 cells (Mr 64,000, 72,000, 80,000, and 320,000), several (Mr 64,000, 72,000, and 80,000) were found to be substantially less phosphorylated in the presence of Li+. Neither a phorbol ester tumor promotor nor permeant cAMP analogs reversed the inhibitory effects of Li+ on neurite outgrowth or on phosphorylation of the component of Mr 64,000. Microtubules are a major and required constituent of neurites, and MAPs may regulate the assembly and stability of neuritic microtubules. The observation that Li+ selectively inhibits NGF-induced neurite outgrowth and MAP phosphorylation suggests a possible causal relationship between these two events. PMID- 4030897 TI - The calcium-dependent myoblast adhesion that precedes cell fusion is mediated by glycoproteins. AB - Presumptive myoblasts from explants of chick embryo pectoral muscle proliferate, differentiate, and fuse to form multinucleate myotubes. One event critical to multinucleate cell formation is the specific adhesion of myoblasts before union of their membranes. In the studies reported here five known inhibitors of myotube formation--trifluoperazine, sodium butyrate, chloroquine, 1,10 phenanthroline, and tunicamycin--were tested for their effect on the Ca++-dependent myoblast adhesion step. The first four inhibitors of myotube formation do not perturb myoblast adhesion but rather block fusion of aggregated cells, which suggests that these agents perturb molecular events required for the union of the lipid bilayers. By contrast, tunicamycin exerts its effect by inhibiting the myoblast adhesion step, thereby blocking myotube formation. The effect of tunicamycin can be blocked by a protease inhibitor, however, which implies that the carbohydrate residues protect the glycoproteins from proteolytic degradation rather than participate directly in cell-cell adhesion. Whereas trypsin treatment of myoblasts in the absence of Ca++ destroys the cells' ability to exhibit Ca++ dependent adhesion, the presence of Ca++ during trypsin treatment inhibits the enzyme's effect, which suggests that myoblast adhesion is mediated by a glycoprotein(s) that has a conformation affected by Ca++. Finally, myoblast adhesion is inhibited by an antiserum raised against fusion-competent myoblasts. The effect of the antiserum is blocked by a fraction from the detergent extract of pectoral muscle that binds to immobilized wheat germ agglutinin, which again suggests that glycoproteins mediate Ca++-dependent myoblast adhesion. PMID- 4030899 TI - Structure of the Chlamydomonas agglutinin and related flagellar surface proteins in vitro and in situ. AB - Using the quick-freeze, deep-etch technique, we compare the structure of the cane shaped plus and minus sexual agglutinin molecules purified from gametes of Chlamydomonas reinhardi. We also describe the structure of three additional gamete-specific fibrillar molecules, called short canes, loops, and crescents, which are structurally related to the agglutinins. Four non-agglutinating mutant strains are found to produce the three latter fibrils but not canes, supporting our identification of the cane-shaped molecule as the agglutinin. The heads of the plus and minus canes are shown to differ in morphology. Moreover, two treatments that inactivate the plus agglutinin in vitro--thermolysin digestion and disulfide reduction/alkylation--bring about detectable structural changes only in the head domain of the cane, suggesting that the head may play an indispensible role in affecting gametic recognition/adhesion. We also present quick-freeze, deep-etch images of the flagellar surfaces of gametic, vegetative, and mutant cells of Chlamydomonas reinhardi. The gametic flagella are shown to carry the canes, short canes, loops, and crescents present in in vitro preparations. The cane and crescent proteins self-associate on the flagellar surface into stout fibers of uniform caliber, and they align along the longitudinal axis of the flagellum. The short canes and loops co-purify with flagella but, in the presence of mica, dissociate so that they lie to the sides of the flagella. The agglutinin canes of both mating types are oriented with their hooks at the membrane surface and their heads directed outward, where they are positioned to participate in the initial events of sexual agglutination. PMID- 4030900 TI - Binding of antibodies in liposomes to extracellular matrix antigens. AB - We have incorporated antibodies against fibronectin or laminin into liposomes and studied their interaction with insoluble forms of these antigens. The antibodies, after modification by palmitoylchloride, were incorporated into the lipid bilayer by the cholate dialysis method. The antibodies in the liposomes recognized their specific antigen with little reaction to the alternative attachment protein or to albumin (less than 2%). The binding of antibody-containing liposomes to insoluble antigen was inhibited by soluble antibodies to the respective antigens but not by antibodies to other antigens. The affinity constant of the liposome-antibody complex with the antigen was estimated at 1-10 X 10(-9) M liposomes. Thus, antibodies in liposomes retain their reactivity and specificity, and the reaction constant is comparable to that observed for immune complexes. PMID- 4030898 TI - Purification of a factor that promotes neurite outgrowth: isolation of laminin and associated molecules. AB - When culture medium, conditioned by any of several cell types, is applied to a polycationic substratum, a substance is adsorbed that causes neurons cultured on that substratum to extend processes (neurites) rapidly and profusely. We have purified the factor responsible for this effect from medium conditioned by bovine corneal endothelial cells, and have shown that it is composed of the glycoprotein laminin and two associated laminin-binding molecules: a sulfated protein known as entactin, and a large heparan sulfate proteoglycan. Of these molecules, only laminin was found to be present throughout the purification in all fractions possessing neurite outgrowth-promoting activity and absent from all fractions lacking activity. Laminin, purified from other sources, has been shown previously to promote extensive outgrowth by cultured neurons. These and other data presented here support the conclusion that laminin is responsible for the neurite outgrowth-promoting activity of the conditioned medium factor. Evidence is also presented that the association of a proteoglycan with laminin promotes efficient attachment of laminin to polycationic substrata, particularly in the presence of competing molecules. PMID- 4030901 TI - Biosynthesis of collagen. AB - During the biosynthesis and assembly of collagen structures, disulfide links can serve several functions. During biosynthesis they successively stabilize intrapeptide folding and associations of three chains into one molecule. Studies on the refolding and reassociation of reduced and denatured carboxyl propeptides of procollagen I showed that successive interactions of folding and assembly are successively weaker. Disulfide bridges were reestablished within correctly refolded carboxyl propeptides. Rearrangements of disulfide bridges may occur during the processing of type V procollagen molecules as these collagens become incorporated into extracellular matrix. The basement membrane procollagen IV molecules become disulfide linked at each end into networks, and there are indications that further rearrangements of disulfide links may allow additional modulation. PMID- 4030902 TI - Deposition of type X collagen in the cartilage extracellular matrix. AB - In cultured chick embryo chondrocytes, type X collagen is preferentially deposited in the extracellular matrix, the ratio between type II and type X collagen being about 5 times higher in the culture medium than in the cell layer. When the newly synthesized collagens deposited in slices from the epiphyseal cartilage of 17-day-old embryo tibiae were isolated, type X collagen was always the major species. In agreement with this result the mRNA for type X collagen was the predominant mRNA species purified from the same tissue. When the total collagen (unlabeled) deposited in the epiphyseal cartilage was analyzed, it was observed that type X collagen represented only 1/15 of the type II collagen recovered in the same preparation. The possible explanations for these differences are discussed. PMID- 4030903 TI - Differentiation in Trypanosoma brucei: host-parasite cell junctions and their persistence during acquisition of the variable antigen coat. AB - Acquisition of the variable antigen-containing surface coat of Trypanosoma brucei occurs at the metacyclic stage in the salivary glands of the tsetse fly vector. The differentiation of the metacyclic trypanosome in the gland has been studied by scanning electron microscopy and by transmission electron microscopy of thin sections and freeze-fracture replicas. The uncoated epimastigote trypanosomes (with a prenuclear kinetoplast) divide while attached to the salivary gland epithelium brush border by elaborate branched flagellar outgrowths, which ramify between the host cell microvilli and form punctate hemidesmosome-like attachment plaques where they are indented by the microvilli. These outgrowths become reduced as the epimastigotes transform to uncoated trypomastigotes (with postnuclear kinetoplast), which remain attached and capable of binary fission. The flagellar outgrowths disappear but the attachment plaques persist as the uncoated trypomastigotes (premetacyclics) stop dividing and acquire the surface coat to become 'nascent metacyclics'. Coat acquisition therefore occurs in the attached trypanosome and not, as previously believed, after detachment. Coating is accompanied by morphological changes in the glycosomes and mitochondrion of the parasite. Freeze-fracture replicas of the host-parasite junctional complexes show membrane particle aggregates on the host membrane but not on the parasite membrane. It is suggested that disruption of the complex occurs when maximum packing of the glycoprotein molecules has been achieved in the trypanosome surface coat, releasing the metacyclic trypanosome into the lumen of the gland. PMID- 4030904 TI - A novel procedure for pattern analysis of features present on freeze-fractured plasma membranes. AB - We have used statistical methods for the analysis of two-dimensional point patterns to derive quantitative descriptions of the distributions of caveolae on freeze-fractured muscle fibre membranes. One method was based on a quadrat analysis while the second was a new procedure that we have called the interpoint distance analysis. We show that the latter analysis can unambiguously distinguish random, clustered and dispersed patterns and that a single parameter can be derived that can be used to compare different distributions. It is readily applicable to patterns containing several hundred points. Practical details of the method are given and a simple algorithm that can be implemented on a microcomputer is provided. The interpoint distance analysis should prove generally useful in situations where the two-dimensional distribution of objects has to be quantified. PMID- 4030905 TI - Apoptosis as the mode of cell death in antibody-dependent lymphocytotoxicity. AB - A light and electron microscopic study of antibody-dependent lymphocytotoxicity was carried out with the object of elucidating the mechanisms responsible for the cell killing, the basis for the research being the relationship that has recently been shown to exist between the morphology of cell death and its pathogenesis. Chang liver cells coated with a rabbit anti-human antibody were used as targets and normal human peripheral-blood lymphocytes as effector cells. Cytotoxicity assays using release of 51Cr demonstrated extensive K-cell killing, thus validating the suitability of the model for morphological studies. Cell death displaying the features of apoptosis correlated with K-cell activity. A small amount of cell death by classical necrosis was observed, but its extent appeared to be unrelated to the presence of lymphocytes, to pre-treatment of the target cells with antibody, or to the magnitude of 51Cr release. The results support evidence indicating that lymphocytotoxicity depends on activation of a self destruct program within the target cell. They do not favour a mechanism involving the production of plasma membrane lesions analogous to those responsible for complement-mediated immune cytolysis. PMID- 4030906 TI - A mutant of Chlamydomonas reinhardtii that lacks the flagellar outer dynein arm but can swim. AB - A new type of Chlamydomonas mutant, which lacks the outer dynein arm but can swim, was isolated. Sodium dodecyl sulphate/polyacrylamide gel electrophoresis showed that four of the ten high-molecular-weight bands of dynein present in the wild-type axoneme are missing or diminished in the mutant axoneme. The mutant has a swimming rate of about 35 micrometers/s and a flagellar beat frequency of about 25 Hz, both of which are about 1/2.5 to 1/3 of those of the wild type. The mutant flagella beat with an asymmetric, cilia-type pattern, similar to the forward swimming mode of the flagellar beating pattern of the wild type. However, unlike wild-type flagella, the mutant flagella never beat with a symmetrical waveform: when the cells were stimulated by intense light, the mutant transiently stopped beating its flagella, whereas the wild-type cell transiently swam backwards with the two flagella beating with a symmetrical waveform. Both wild-type and mutant cells could be demembranated by Nonidet P40 and their swimming reactivated by addition of Mg-ATP in the virtual absence of Ca2+. Double reciprocal plots of the beat frequency against ATP concentrations showed a linear relationship for both strains, yielding maximal frequencies of 44 Hz (wild-type) and 23 Hz (mutant). The mutant axonemes can be reactivated only when the Ca2+ concentration is lower than 10(-6) M: at pCa4, the wild-type axonemes beat with a symmetrical waveform, but the mutant axonemes showed no movement. These findings indicate that the outer dynein arm is dispensable for flagellar beating of the asymmetric waveform (forward-swimming mode), but not for beating of the symmetrical waveform (backward-swimming mode), and thus suggest the importance of the outer dynein arm in the switching of flagellar waveforms. PMID- 4030907 TI - Production and functional properties of eosinophils from bone marrow cultures. AB - Bone marrow cultures have been established from mice infected with Mesocestoides corti and undergoing parasitic eosinophilia. In the absence of added conditioned medium, eosinophil differentiation ceases, and eosinophils are undetectable by 7 days, whereas neutrophil production continues over several weeks as with normal bone marrow. Eosinophil production can be induced by adding pokeweed mitogen stimulated spleen supernatants (MSSS) or specific antigen-stimulated spleen supernatants (ASSS) produced from-spleen cells of M. corti-infected mice. In contrast to the continuous production of neutrophils, eosinophil production is transient, suggesting that there is no continued production of eosinophil progenitor cells in these cultures. More eosinophils are produced when MSSS is added at the initiation of cultures, compared to after a delay of 2 weeks, and establishing the cultures at 33 degrees C does not appear to enhance eosinophil production. The eosinophils produced are shown to express the eosinophil differentiation antigen defined by monoclonal antibody NIMP-R13, they produce eosinophil peroxidase in similar amounts to eosinophils taken from mice. They show normal phagocytic activity of antibody-coated erythrocytes and lyse red cells coated with antibodies of IgG1, IgG2a, IgG2b, but not IgM isotypes. PMID- 4030908 TI - The transcriptional activity of individual ribosomal DNA gene clusters is modulated by serum concentration. AB - The activity of ribosomal gene clusters has been studied by cytological methods in human cultured cells grown in different amounts of serum under controlled experimental conditions. It has been shown that increasing amounts of serum induce an increase in ribosomal RNA synthesis at the single cell level. Furthermore, the concomitant identification of individual rRNA gene clusters by fluorescent techniques allowed us to demonstrate: (1) that individual gene clusters have differential transcriptional activity and differential frequency of activation; (2) that ribosomal gene activity is closely associated with the amount of silver-positive gene product and; (3) that environmental variations modulate rRNA synthesis by repressing or derepressing specific gene clusters. PMID- 4030909 TI - Correlations between characteristics of some free-living Chlorella sp. and their ability to form stable symbioses with Hydra viridis. AB - Aposymbiotic polyps of Hydra viridis were infected with 17 strains of in vitro cultured Chlorella sp. Larvae of Artemia fed with the chlorellae were used as an infecting vector. Of the 17 strains, seven formed stable symbioses and one formed a transient infection that disappeared within several weeks. Chlorellae of the nine other strains were cleared out of the infected hydra within 2-3 days. There was a distinct correlation between the ability of the chlorellae to form stable symbioses and their ability to adapt and grow in media enriched with 0.5% proteose peptone. Only strains that grew in the latter medium formed symbioses with the hydra. The symbioses formed with the different strains of chlorellae differed from one another. Hydra infected with some strains greened completely while those infected with other strains greened only partially. The degree of infection varied also within each population, and there were differences in the distribution of the various chlorellae along the stalk and inside the digestive cells of the hydra. Growth rates of the infected hydra were all less that those of aposymbiotic hydra or of hydra hosting native zoochlorellae. We conclude that adaptability to a nutrient-rich environment inside the perialgal vacuole of the digestive cell and a sufficient growth rate therein are crucial to the ability of chlorellae to form stable symbioses with H. viridis. In time, co-adaptation of hydra and chlorellae would restore the normal growth rate of the former and bring about regularity to the form and extent of infection by the latter. PMID- 4030910 TI - Morphological changes in rat tracheal cells during the adaptive and early growth phase in primary cell culture. AB - The purpose of our studies was to determine the fate of different cell types present in early primary cultures of tracheal epithelial cells and, if possible, to elucidate the role they play in the establishment of the cultures. Epithelial cells were isolated from rat tracheas with 0.5% Pronase and were cultured on collagen-coated dishes as described previously. Light and transmission electron microscopic studies showed that the cell population harvested from rat trachea was composed of approximately 30% ciliated cells, 50% granule-containing cells and 20% undifferentiated cells (presumably basal cells). Upon seeding the tracheal cell suspensions into culture, approximately 40% of the cells attached. Cell attachment was virtually complete after 16 h. Roughly 60% of the cells attaching during the first 12 h were neither ciliated nor granulated, suggesting that undifferentiated cells played a major role in establishment of the early cultures. Between 20 and 35% of the cells attaching during this time were identified as granulated cells (mucous cells). Ciliated cells did not start to attach in significant numbers until 8 h after seeding. They never amounted to more than 8-12% of the attached cell population. After 12 h of culture, the cell population underwent a progressive loss of differentiation. The number of poorly differentiated cells (i.e. those showing neither cilia nor mucous granules) increased correspondingly. This loss of differentiation preceded the onset of DNA synthesis and cell growth which began at about 24 and 40 h, respectively. Continuous [3H]thymidine-labelling studies showed that at 48 h after the start of culture about 90% of all attached cells had entered DNA synthesis at least once. This finding is consistent with the interpretation that the ciliated cells are terminally differentiated cells and are probably the only part of the tracheal cell inoculum not participating in the growth of the cultures. At 72 h, the cultures (now in mid-log growth phase) were composed of uniformly undifferentiated cells lacking cilia and mucous granules. The cells nevertheless showed unequivocal epithelial characteristics such as tight junctions and desmosomes. The studies suggest that both basal and mucous cells are responsible for the establishment and growth of the rat tracheal epithelial cell cultures. PMID- 4030911 TI - Inhibition of cell spreading on the band of extracellular fibres in early chick and quail embryos. AB - The ventral surface of the upper layer shows a band of extracellular fibrils around the anterior and lateral border of the area pellucida during gastrulation of the chick embryo. Using scanning electron microscopy, we found that this disposition is correlated with the motility of the middle-layer cells of gastrulating chick and quail embryos. Outside the fibrous band, single middle layer cells and a sheet of mesoblast cells were spread out and possessed lamellae. Single cells on the fibrous band did not form lamellae. The same cell behaviour was obtained with the explants of deep layer on the fibrous band. The fibrous band is assumed to operate as a barrier that inhibits cell motility during gastrulation. PMID- 4030912 TI - Circadian rhythm of nucleoli in rat superior cervical ganglion neurons: the two types of fibrillar centres and their quantitative relationship with the nucleolar organizing regions. AB - A quantitative stereological analysis was undertaken in nucleoli of rat superior cervical ganglion neurons. In this model, two types of fibrillar centres were observed: (1) small-type fibrillar centres were observed during the light span; and (2) a single large-type fibrillar centre occurred during the dark span near the smaller ones. The present data showed that the drastic increase in the mean volume of fibrillar centres during the dark span involved the occurrence and the progressive enlargement of one single large-type fibrillar centre and a marked rise in the number of small-type centres from 18 +/- 2 to 74 +/- 5 at 1500 h and 0100 h corresponding to light and dark spans, respectively. The total number of these small-type fibrillar centres per nucleolus increased with the total volume whereas their unit volume remained unchanged. This enabled us to establish some relationship with nucleolar organizing regions (NORs). PMID- 4030914 TI - Normal average value of cerebral blood flow in younger adults is 50 ml/100 g/min. PMID- 4030913 TI - The ultrastructural organization of proteoglycans and collagen in human and rabbit scleral matrix. AB - The distribution of proteoglycans and their association with collagen fibrils were studied in human and rabbit sclera following fixation of tissue in glutaraldehyde containing Cuprolinic Blue, a specific stain for proteoglycans when used in the presence of critical concentrations of electrolytes. Proteoglycans were visualized by electron microscopy as fine filaments, approximately 54 nm in length and 5 nm in diameter, associated with the d band in the gap zone of the periodic collagen banding pattern. Filaments were present in three orientations: (1) radiating from the d band to associate with corresponding sites on adjacent collagen fibrils; (2) encircling the collagen fibril at the d band position; and (3) lying along the fibril axis, often linking consecutive d bands. No difference was apparent between the proteoglycan-collagen organization in human and rabbit sclera. A similar arrangement of proteoglycan filaments in association with the d band was also evident throughout all levels of the sclera in spite of considerable variations in fibril diameter from inner to outer stroma. Furthermore, the specific relationship of proteoglycans with the collagen fibrils in sclera closely resembled that previously described in tendon and in articular cartilage, lending support to the view that the association of proteoglycans with collagen may be consistent in a majority of connective tissues, irrespective of their diverse functional specializations. PMID- 4030915 TI - In vivo measurement of regional brain and tumor pH using [14C]dimethyloxazolidinedione and quantitative autoradiography. AB - Using [14C]dimethyloxazolidinedione ([14C]-DMO) and quantitative autoradiography, we estimated tissue pH (pHt) and intracellular pH (pHi) in nine regions of the normal rat brain and in intracerebrally implanted RG-2 gliomas. Calculations of regional pHt, based on equilibrium tissue and arterial plasma [14C]DMO concentration, ranged from 6.83 to 6.94; pHi, calculated assuming an extracellular water volume of 0.15 ml/g for gray matter and 0.11 ml/g for white matter, ranged from 6.61 to 6.78. No consistent difference was found in pHt or pHi between white and gray matter regions. Tumor tissue water content was determined by drying to constant weight, and extracellular space water volume (Ve) was estimated with [14C]sucrose in nephrectomized rats using quantitative autoradiography. Tumor pHt ranged from 7.08 to 7.18. For Ve = 0.17 (measured), pHi was 6.94-7.06; for Ve = 0.30 (assumed), the corresponding range for pHi was 6.63-6.90. Thus, the RG-2 glioma is not more "acidic" than adjacent brain tissue and its "alkaline" pHt probably reflects a large extracellular water content and plasma-like extracellular pH. PMID- 4030917 TI - Kinetics of saturable transport across the blood-brain barrier. AB - This article is concerned with the extension of the Renkin-Crone model to a case of saturable transport across the blood-brain barrier, i.e., when the apparent permeability-surface area product is concentration dependent. A well-mixed tissue compartment is assumed, together with a simple symmetric saturable transport system. A computation scheme, or algorithm, is described that allows the calculation of arteriovenous differences and net influx rates for parent substance and tracer in terms of arterial and tissue concentrations of each, the transport maximum Tmax, the half-saturation constant Kt, and plasma flow rate. The scheme was devised initially for the analysis of experiments in which the parent substance was not in a steady state and in which tracer backflux from tissue to capillary was significant. PMID- 4030916 TI - Cerebral atrophy and hypoperfusion improve during treatment of Wernicke-Korsakoff syndrome. AB - Nineteen patients with sudden onset of impaired recent memory, cerebellar ataxia, peripheral neuropathy, and other signs of Wernicke-Korsakoff syndrome (WKS) were treated and examined prospectively for 3 months. Serial studies included histories, neurological examinations, cognitive capacity screening examinations (CCSE), computed tomography (CT) scans, and measurements of regional CBF. Patients were detoxified and withdrawn from sedatives before CBF measurements were examined. Treatment included alcohol withdrawal, nutritious diet, and 300 mg thiamine daily. Before treatment CCSE scores and blood flow values of both white and gray matter were reduced, particularly within both temporoparietal regions. After treatment of compliant patients (n = 10), white and gray matter blood flow increased concurrently with improved CCSE scores. Abnormal eye signs, ataxia, peripheral neuropathy, and performance of activities of daily living also improved. Cerebral atrophy and ventricular enlargement measured by CT decreased. Early recognition and treatment of WKS in compliant patients permit rapid reversals of cognitive and neurological impairments associated with increased blood flow of gray and white matter and improvements of brain atrophy measured by CT scanning. PMID- 4030918 TI - Ischemia-induced shift of inhibitory and excitatory amino acids from intra- to extracellular compartments. AB - Brain ischemia was induced for 10 or 30 min by clamping the common carotid arteries in rabbits whose vertebral arteries had previously been electrocauterized. EEG and tissue content of high energy phosphates were used to verify the ischemic state and to evaluate the degree of postischemic recovery. Extracellular levels and total contents of amino acids were followed in the hippocampus during ischemia and 4 h of recirculation. At the end of a 30-min ischemic period, GABA had increased 250 times, glutamate 160 times, and aspartate and taurine 30 times in the extracellular phase. The levels returned to normal within 30 min of reflow. A delayed increase of extracellular phosphoethanolamine and ethanolamine peaked after 1-2 h of reflow. Ten minutes of ischemia elicited considerably smaller but similar effects. With respect to total amino acids in the hippocampus, glutamate and aspartate decreased to 30-50% of control while GABA appeared unaffected after 4 h of reflow. Alanine, valine, phenylalanine, leucine, and isoleucine increased severalfold. The importance of toxic extracellular levels of excitatory amino acids, as well as of high extracellular levels of inhibitory amino acids, are considered in relation to the pathophysiology of neuronal cell loss during cerebral ischemia. PMID- 4030919 TI - Ischemic brain damage in rats following cardiac arrest using a long-term recovery model. AB - A model is described in which transient complete cerebral ischemia is induced in rats by intracardiac injection of potassium chloride. The animals were intubated and mechanically ventilated with a nitrous oxide/oxygen (70:30) mixture. Cardiac arrest was achieved following a brief period of ventricular fibrillation. After 5 6 min, the circulation was restored by cardiopulmonary resuscitation and partial exchange transfusion. Local CBF (LCBF) during ischemia and cardiac resuscitation was studied by injection of [14C]iodoantipyrine into the right auricle at various periods during cardiac arrest, and was subsequently analyzed by autoradiography. No radioactive tracer could be visualized in any brain structure, demonstrating the absence of CBF during the cardiac standstill. LCBF was also studied at 5 min and 6.5 h after cardiac resuscitation. Five minutes of recirculation showed an increase in blood flow in all brain structures studied, ranging between 130 and 400% of control values. After 6.5 h of recirculation, the CBF was decreased in 13 of 24 brain structures by 20-50%, concomitantly with the depressed rate of glucose utilization found in 15 brain structures. The neocortical, hippocampal, and striatal concentrations of labile phosphates, lactate, pyruvate, phosphocreatine, glucose, and glycogen were measured 5 min after cardiac arrest. Extensive energy failure and elevation of lactate levels were observed and were similar to earlier reported values. One week following recovery from the ischemic insult, the animals were perfusion-fixed with formaldehyde. The brains were embedded in paraffin, subserially sectioned, and stained with cresyl violet/acid fuchsin. Histopathological changes were assessed by light microscopy as the number of acidophilic or pyknotic neurons. Morphological changes were observed in the hilus of the dentate gyrus, the hippocampal CA1 and subicular regions, the dorsal and lateral septum, the olfactory tubercle, the primary olfactory cortex, the entorhinal cortex, the amygdaloid nuclei, and the reticular nucleus of the thalamus. The distribution of the morphological changes suggests a transsynaptic mechanism, causing neuronal necrosis primarily in the limbic brain areas. PMID- 4030920 TI - Brain tissue acidosis and changes of energy metabolism in mild incomplete ischemia--topographical study. AB - Regional changes of brain tissue pH and its correlation to energy metabolism were studied in various degrees of incomplete ischemia for 5 and 60 min in the unilateral common carotid occlusion of normally fed mongolian gerbils. The degree of ischemia was evaluated by the severity of neurological deficits following 60 min of occlusion, and animals were divided into three groups: symptomatic, borderline, and asymptomatic. Changes of NADH and ATP distribution corresponded well to the degree of ischemia. On the other hand, acidosis developed more clearly and extended in wider areas than the changes of NADH and ATP distribution. These changes were already seen at 5 min of occlusion. From the results of this experiment, it was suspected that acidosis in mild incomplete ischemia was due to stimulated anaerobic glycolysis that might supplement NADH oxidation and ATP yields. Further, acidosis without energy failure was considered not to be detrimental to neuronal cells. PMID- 4030921 TI - Influence of reduced oxygen availability on cerebral metabolic changes during bicuculline-induced seizures in rats. AB - The objective of the present work was to study cerebral energy metabolism at threshold levels of hypoxia, i.e., degrees of hypoxia that abolish cerebral electrical activity, in the "normal" and in the epileptic brain. Seizures were induced by intravenous bicuculline and cerebral oxygen availability was reduced by a combination of lowered PO2 and reduced blood pressure to give a transformation of the burst suppression pattern to either one with single spikes or overt EEG flattening. Nonepileptic control animals were exposed to degrees of hypoxia that gave either a markedly depressed EEG pattern with sparse slow waves or EEG flattening. Epileptic and nonepileptic groups proved comparable in terms of calculated oxygen availability and cerebral oxygen consumption at the threshold of "transmission failure." At levels of hypoxia that markedly attenuated or completely abolished seizure discharge, the cerebral metabolic changes were more marked than in comparable nonepileptic animals. These changes comprised an imminent severe perturbation of cerebral cortical phosphorylation potential, a pronounced lactic acidosis with a precipitous redox change, and a marked accumulation of ammonia. The more labile energy balance of the epileptic brain may indicate that the "seizure state" either increases cellular energy demands in spite of the electrical silence or reduces the efficiency of ATP production at the prevailing oxygen availability. It is conceivable that energy failure elicited by complicating hypoxia can aggravate or precipitate brain cell damage in epilepsy. PMID- 4030922 TI - Blocking effect of diltiazem on thiopentone-induced vasoconstriction in isolated canine internal carotid arteries. AB - Stainless-steel cannulas were inserted into isolated internal carotid arteries of the dog to observe vasoconstrictor responses to thiopentone. Thiopentone at a relatively large dose (100-3,000 micrograms) induced vasoconstrictor responses in a dose-dependent manner. A dose of 1 mg thiopentone usually produced a definite increase in perfusion pressure of greater than 50 mm Hg. These effects were not influenced by treatment with phentolamine in doses that significantly suppressed noradrenaline-induced vasoconstrictor responses. Diltiazem inhibited the constriction in response to thiopentone as well as that to potassium chloride in a noncompetitive antagonistic manner. It is suggested that the constriction induced by thiopentone may be due in part to activation of the calcium-inward channel in the wall of the internal carotid artery. PMID- 4030923 TI - Effects of enkephalins, morphine, and naloxone on pial arteries during perivascular microapplication. AB - The effects of the opiate receptor agonists, enkephalins and morphine, and the antagonist, naloxone, on cerebrovascular resistance vessels was investigated in situ by employing perivascular microapplication. Feline pial arteries with a resting diameter of 66-294 micron were tested. Vascular diameter was measured using television image splitting. Concentration-response curves revealed no change of diameter when Leu-enkephalin, D-Ala2-Leu-enkephalinamide, D-Ala2-Met enkephalinamide, and morphine were applied in concentrations of 10(-11)-10(-5) M. Considering the concentrations of enkephalins that have been found in natural cerebrospinal fluid or that can be expected in the vicinity of enkephalinergic synapses, the data obtained with the lower concentrations indicate that enkephalins are probably not important for the regulation of pial arterial resistance. At 10(-4) M only the dilation (4.3%) elicited by D-Ala2-Leu enkephalinamide was statistically significant (p less than 0.01). All four agonists at 10(-3) M induced significant dilatations varying between 5.4 and 13.6%. Naloxone exerted no vascular effect per se at 10(-5) and 10(-4) M but a dilatation of 15.3% at 10(-3) M. The latter can be explained by a partial agonist action. During simultaneous administration, naloxone (10(-4) M) reduced the dilatations induced by 10(-4) and 10(-3) M D-Ala2-Leu-enkephalinamide dose dependently. This indicates that mu- and delta-opioid receptors, probably located at the vascular smooth muscle cell, were involved in the mediation of the dilatation induced by the highest concentrations of the compounds. PMID- 4030924 TI - Regional quantitative determination of brain glucose in tissue sections: a bioluminescent approach. AB - A bioluminescent technique is described for the regional quantitative determination of brain glucose. A close linear interrelationship was obtained between the optical density of the bioluminescent images and the glucose content in tissue samples. The regression coefficients of this correlation permit the quantification of glucose bioluminescent pictures using an image-processing system. Regional distribution of glucose was correlated to regional tissue pH under both physiological and pathophysiological conditions. PMID- 4030925 TI - Reversal of neurological deficits by levallorphan in patients with acute ischemic stroke. AB - This study was conducted to examine the effect of the intramuscular injection of levallorphan tartrate (1.0 mg), a mixed agonist-antagonist opiate, on the neurological signs, symptoms, and vital signs in 19 patients with acute ischemic stroke. A temporary improvement of hemiplegia or hemiparesis was observed within several minutes after levallorphan injection in 13 of the patients. There were no significant alterations in blood pressure or pulse rate after injection. The findings indicate that levallorphan may have a temporary improving effect on neurological deficits in acute ischemic stroke. In addition, observation of the response to levallorphan may serve to predict the prognosis of the final neurological outcome in this type of patient. PMID- 4030926 TI - Serotonin depression of local cerebral glucose utilisation after monoamine oxidase inhibition. AB - The major catabolic enzyme for serotonin, monoamine oxidase (MAO), is present in the endothelium of cerebral vessels. We report the effects of the intracarotid administration of serotonin on local cerebral glucose utilisation in rats following MAO inhibition with the drug clorgyline. It was found that saline, clorgyline, or serotonin alone produced no significant changes in glucose utilisation. Following the infusion of clorgyline, the administration of serotonin produced significant decreases in glucose utilisation in cortical areas of between 12 and 33% and in the caudate nucleus of 16%. PMID- 4030927 TI - Low-cost microcomputer-based densitometer. AB - We have constructed low-cost equipment for the measurement of the optical density of x-ray films. This equipment is based on a video system connected via an analog to digital converter to an Apple microcomputer. The optical density of an x-ray film can thus be accessed by commands in BASIC or machine-code programs. By using a calibrated step-wedge film, we have found a stable linear response for optical densities of up to 0.8. PMID- 4030928 TI - Advantages and limitations of isotachophoretic determinations of metabolites in tissue extracts. PMID- 4030929 TI - Isotachophoresis as a candidate reference method in analytical chemistry. Determination of sodium in serum. AB - Isotachophoresis seems a likely candidate for a reference method, as it is more accurate and precise than common routine methods. The response is highly linear and depends on a well defined transport number of the leading ion, stability of the driving current, mobility of the separand, which is well controlled by the leading electrolyte and the use of a high-resolution detector. The suitability of isotachophoresis as a reference method was investigated for the determination of sodium in human serum. The operational conditions were 0.01 M K+/citrate (leading electrolyte) at pH 5.5 and 0.01 M creatinine X HCl (terminating electrolyte). Both n-butylamine and ammediol could be used as internal standards. The calibration graph constructed from standard solutions, diluted by weight with the internal standard, yielded a correlation coefficient of 0.99994 (n = 50) in the working range. The method seems especially useful for the determination of any ionic solute in, e.g., clinical samples (lithium, calcium, creatinine or drugs). PMID- 4030930 TI - Isotachophoresis of allergenic extracts. AB - One aspect of the isotachophoretic determination of protein patterns in biological samples of interest is the characterization of allergens. This group of (glyco) proteins, causing allergic reactions, is used both for diagnosis and in the treatment of allergy. The aim of this investigation was to obtain a maximum amount of information, within one run, on the (glyco)protein composition of a number of allergenic extracts (e.g., from pollen or house dust mites). Commercially available extracts were dialysed prior to analysis to remove disturbing buffer constituents. A high-pH system was chosen in order to obtain a maximum amount of information from the samples (1-2 microliter). The leading electrolyte was 0.01 M C1-, buffered with Tris (pH 8.2), containing 0.2% w/v hydroxyethylcellulose, and the terminating electrolyte was beta-alanine, buffered to pH 10 with Ba(OH)2. The total analysis time was 15-20 min using a PTFE capillary (0.2 mm I.D.). The pre-separation current was 30 microA and the current during detection was 15 microA. UV absorption was measured at 280 nm. For optimal discrimination of the compounds of interest, an ampholyte mixture was used for spacing. The analytical procedure yielded highly reproducible UV patterns. Significant differences between various allergenic extracts were observed. It was concluded that isotachophoresis is a powerful method for the physico-chemical characterization of individual allergenic extracts, e.g., with respect to manufacturing and quality control. PMID- 4030931 TI - Determination of quinine in beverages, pharmaceutical preparations and urine by isotachophoresis. AB - The suitability of isotachophoresis for the determination of quinine in different samples was investigated. The operational conditions were 0.01 M potassium morpholinoethanesulphonic acid (MES) (pH 6.0) with 0.05% Mowiol as the leading electrolyte and ca. 0.005 M creatinine-MES as the terminating electrolyte. The analyses were carried out at 25 microA in a 0.2 mm I.D. PTFE capillary with UV and conductivity detection. Quinine-containing beverages were degassed by sonification and directly injected. The limit of detection was 5 mg/l with a 4 microliter injection volume. The allowed concentrations could be determined with sufficient accuracy. Analgesic preparations were dissolved in a solution of 5 X 10(-3) M MES with sonification. The quinine levels found agreed well with the declared values. The other constituents of the pharmaceuticals did not interfere with the analysis. Urine samples from volunteers were analysed after consumption of tonic. The samples were extracted with dichloromethane-isopropanol (95:5), vortexed, centrifuged, evaporated to dryness, the residue dissolved in 5 X 10(-3) M MES and analysed. At a concentration factor of 33, the limit of detection was ca. 60 micrograms in 48-h urine: 2-15% of the quinine consumed was excreted as the parent compound in the first 48 h after consumption. The combination of the extraction procedure and the operational system makes the method suitable for the determination of a number of other alkaloids in physiological samples. PMID- 4030932 TI - Analytical capillary isotachophoresis: a routine technique for the analysis of lipoproteins and lipoprotein subfractions in whole serum. AB - A capillary isotachophoretic separation technique was developed for lipoproteins in native serum which, compared with previous electrophoretic techniques, has negligible molecular sieve effects, does not need gel casting, is suitable for whole serum and has a high discriminative power for lipoprotein subfractions. The technique is based on pre-staining whole serum lipoproteins for 30 min at 4 degrees C before separation of 0.5 microliter of the sample in a free-flow capillary system (0.5 mm I.D.) with discontinuous buffer system. In normolipidaemic sera, high-density (HDL) and low-density lipoproteins (VLDL) are separated into two major subpopulations according to their net electric mobility. The identification of these fractions was confirmed by substitution with ultracentrifugally isolated lipoproteins and by their complete absence from Tangier and abetalipoproteinaemic serum. Triglyceride-rich very low-density lipoproteins (VLDL) revealed a defined zone between the HDL and LDL subpopulations. Our preliminary results indicate that the separation of human whole serum lipoproteins by capillary isotachophoresis is a promising method for the determination of lipoprotein subfractions. PMID- 4030933 TI - Determination of heavy metals by isotachophoresis. AB - The suitability of isotachophoresis for the analysis of metals in, e.g., environmental samples was studied. In a cationic operational system the heavy metals Fe, Cu, Ni, Cd, Co, Zn, Pb and Mn were simultaneously determined. The separation was achieved through complex formation with one of the counter ions, hydroxyisobutyric acid. The other counter ion was acetic acid, the leading ion was 0.02 M potassium or sodium (pH 4.1) and the terminator was H+. The analysis time was 15 min at 60 microA in a 0.2 mm I.D. capillary. Aqueous samples containing ppm and ppb amounts were enriched on a cation exchanger with an extremely low affinity for sodium (Chelex 100). Good recovery, linearity, precision and accuracy were obtained even down to the ppb range. Although the sensitivity of the method is not greater than that of some of the more established methods for the individual metals, a great advantage of isotachophoresis is the simultaneous determination of the metals, with equal response factors. An example is given of the determination of metals, including aluminium, in serum. PMID- 4030934 TI - Micropreparative isotachophoretic electrodesorption of monoclonal antibodies from an affinity adsorbent. AB - The principle of isotachophoretic desorption of proteins from an affinity sorbent was used for the preparative isolation of monoclonal antibodies against transferrin, under a cationic regimen. Electrodesorption was carried out on an apparatus of our own construction with a photometric detector and a detector of potential gradient. The apparatus was provided with a sorption element filled with an exchangeable affinity active sorbent. The construction of the apparatus and the procedure suitable for the isolation of the antibody of the IgG type are described. The possibility of repeating the sorption-desorption cycle at least sixteen times was demonstrated, with relatively good yields of the protein. PMID- 4030935 TI - Large sample volume preseparation for trace analysis in isotachophoresis. AB - An isotachophoretic device for the analysis of trace components in a sample with the efficient pre-separation and elimination of bulk components has been suggested and realized. A large volume of the sample in question is separated in a rectangular wide-bore channel packed with a suspension of a granulated polyacrylamide gel and analyzed in free electrolytes in a narrow-bore tube. Trace components, the concentrations of which are 10(-6) mol/l, can be analyzed in 60 70 min applying ca. 1 ml of the sample even in the presence of bulk excess of a major component the concentration of which is by 5 orders of magnitude higher. PMID- 4030936 TI - Microbore packed-column anion-exchange liquid chromatography of nucleobases, nucleosides and nucleotides. AB - Low-capacity anion-exchange resin was packed into a 45 cm X 0.19 mm I.D. fused silica tubing and applied to micro-column liquid chromatography of nucleobases, nucleosides and isomers of nucleotides. The effects of the chromatographic conditions on the elution behaviour of these compounds were studied. The efficiency of the microbore packed column was comparable with that of the conventional size column. PMID- 4030937 TI - Analysis of antitumour [1,1-bis(aminomethyl)cyclohexane]platinum(II) complexes derived from spiroplatin by high-performance liquid chromatography with differential pulse amperometric detection. AB - A reversed-phase high-performance liquid chromatographic analysis was developed for aqua[1,1-bis(aminomethyl)cyclohexane]sulphatoplatinum(II) (spiroplatin) and its hydrolysis and oligomerization products. The platinum complexes were detected by differential pulse amperometry at a hanging mercury drop electrode, at -540 mV vs. Ag/AgCl. The limit of detection was 0.05 microM. Aqueous solutions of spiroplatin appeared to contain the diaqua, monoaquamonosulphato, monoaquamonochloro, dichloro and hydroxo-bridged dimer complexes of [1,1 bis(aminomethyl)cyclohexane]platinum(II) in mutual equilibrium. The equilibrium shifts after dilution in infusion fluids were studied. Detection of these platinum(II) complexes in untreated human plasma ultrafiltrate and urine demonstrated the selectivity of the described analysis. PMID- 4030938 TI - Fourth International Symposium on High-Performance Liquid Chromatography of Proteins, Peptides and Polynucleotides. Baltimore, MD, December 10-12, 1984. Part I. PMID- 4030939 TI - High-performance liquid chromatographic investigations on some enzymes of papaya latex. AB - Papaya latex and commercial chymopapain have been examined by cation-exchange chromatography on a TSK SP 5PW column. Multiple components are observed and the resolution is superior to that obtained by low-pressure ion exchange. Most components display amidase activity. Fractions obtained from chymopapain by preliminary chromatography on SP-Sephadex have also been examined by the same procedure and by N-terminal and amino acid analysis. The results are consistent with the existence of chymopapain in multiple forms, the proportions of which alter. The chromatographic profile of chymopapain is influenced by the presence of cysteine in the sample. PMID- 4030941 TI - Purification of a uridine-specific acid nuclease from chicken liver by fast protein liquid chromatography. AB - A rapid purification procedure for a novel uridine-specific nuclease from chicken liver based on the Pharmacia fast protein liquid chromatography (FPLC) system is presented. The purification was achieved by applying crude extract to a Mono S cation-exchange column equilibrated with 10 mM potassium phosphate buffer (pH 6.0). The enzyme was eluted in 20 min with a potassium chloride gradient at a flow-rate of 2 ml/min. The enzyme was then chromatographed on a Superose 12 size exclusion column in less than 1 h at a flow-rate of 0.5 ml/min (Kav = 0.77). The enzyme was re-chromatographed on a second Mono S column to concentrate the protein. The uridine-specific nuclease hydrolyzed poly(U) and Escherichia coli 5S RNA. Poly(A) was hydrolyzed by the nuclease less efficiently (about 10% of the poly(U) activity). No hydrolysis was detected with poly(C), poly(G), poly(dT) or poly(dA) as substrate. The speed with which each purification step could be carried out facilitated the determination of optimal chromatographic conditions. We found that the resolution of the Mono S and Superose 12 columns was superior to that of conventional ion exchangers and size-exclusion columns respectively. PMID- 4030940 TI - Rapid, small-scale preparation of gastrointestinal hormones by high-performance liquid chromatography on a C18 column. AB - A rapid reversed-phase high-performance liquid chromatography method was developed for the isolation of small quantities of biologically active gastrointestinal hormones, using a Varian MCH-10 C18 column. Biologically active secretin was isolated from contamination with other hormones, including cholecystokinin, gastrin, motilin, and vasoactive intestinal polypeptide, from samples of the acid perfusate of canine duodenum and from the crude acetic acid extract of canine antral mucosa containing less than 100 picomoles of secretin. The method also appeared to be suitable for the isolation of cholecystokinin octapeptide and motilin. PMID- 4030942 TI - Analysis of nucleoproteins by direct injection of dissolved nuclei or chromosomes into a high-performance liquid chromatographic system. AB - This work describes the development of a method for fractionating the total nuclear proteins of Chinese hamster cells (line CHO) by high-performance liquid chromatography of whole nuclei or chromosomes. Nuclei or chromosomes were dissolved for 2 h in 6 M guanidine hydrochloride containing 0.2% trifluoroacetic acid (TFA). Residual particulates were removed by centrifugation, and a sample of the solution was passed through a Bio-Sil TSK guard column, followed by a Bio-Sil TSK 400 column, equilibrated with water containing 0.2% TFA. These columns fractionated the sample by adsorbing the DNA, passing the proteins near the exclusion limit, passing the guanidine at the inclusion limit, and passing an unidentified non-protein/non-DNA material after the inclusion limit. The protein peaks from the TSK columns were collected directly on a muBondapak CN reversed phase column. The protein fractions were then eluted from the CN column with an acetonitrile gradient containing 0.2% TFA. Three other reversed-phase columns were examined for use with the TSK columns. The muBondapak C18 Radial-Pak column produced the best resolution of histone variants, while the Zorbax C8 column produced a better resolution of the non-histone proteins. The Nova-Pak C18 Radial Pak column was found to be unsatisfactory for both classes of nucleoproteins. PMID- 4030943 TI - Preparation of sheep and cattle immunoglobulins with antibody activity by high performance liquid chromatography. AB - High-performance anion-exchange chromatography (HPIEC) and high-performance size exclusion chromatography (HPSEC) were used to purify serum IgM and IgG from sheep and cattle. Pooled serum from normal cattle and sheep and serum from sheep, infected with two different viruses, were prepared for HPIEC by chromatography on CM-Affi-Gel Blue. After HPIEC, fractions containing IgG and IgM were pooled and concentrated and further purified by HPSEC. The purity of fractions from HPIEC and HPSEC were evaluated by immunoelectrophoresis, protein-A-Sepharose affinity chromatography, and sodium dodecyl sulphate-polyacrylamide gel electrophoresis. Monoclonal antibody specific for bovine IgG2 was used to assay for IgG2 and IgG2 contamination of other fractions. The antibody activity to ovine adenovirus 5 and to ovine progressive pneumonia virus was assayed by neutralization and immunodiffusion. Antibody activity was retained against both viruses in the fractions containing IgG1 and IgM. This high-performance liquid chromatography procedure was a rapid preparative method to produce specific immunoglobulins and could be used to evaluate the purity of immuno-reagents. PMID- 4030945 TI - Reversed-phase high-performance liquid chromatographic separation of diastereomeric phosphorothioate analogues of oligodeoxyribonucleotides and other backbone-modified congeners of DNA. AB - Diastereomeric phosphorothioate analogues of oligodeoxyribonucleotides, which were synthesized by an automated, solid-phase, phosphoramidite-coupling method, were conveniently separated by reversed-phase high-performance liquid chromatography on a muBondapak C18 column with a gradient of acetonitrile in triethylammonium acetate buffer. These synthetic and chromatographic methods were also used to obtain diastereomerically pure bis-phosphorothioate, alkanephosphonate, and O-alkyl phosphotriester analogues of DNA for exploratory studies of stereochemistry and phosphorolytic enzymes. PMID- 4030944 TI - Isolation of detergent-solubilized monomers of bacteriorhodopsin by size exclusion high-performance liquid chromatography. AB - Bacteriorhodopsin, an integral membrane protein of purple membranes, was solubilized with n-octylglucoside and isolated as intact monomeric micelles by high-performance size-exclusion chromatography. It was shown that separation was obtained between these micelles and either those containing bacterio-opsin or retinal as well as bacterio-opsin in the aggregated state. Estimates of the apparent molecular weights and Stokes radii were obtained by comparison with water-soluble proteins with known properties. Thermal denaturation of the native protein micelle induced the formation of a denatured species, which was similar to that found from denaturation at 4 degrees C. PMID- 4030946 TI - Neonucleoproteins. Preparation and high-performance liquid chromatographic characterization of succinyl-lysozyme-diaminooctyl-polycytidylic acid and related polycytidylic acid conjugates. AB - Transamination conjugates of cytidine-3'-phosphate and polycytidylic acid (poly C) with diaminopropane, diaminohexane and diaminooctane (DAO) are formed both at 25 degrees C and 60 degrees C. The extent of reaction and formation of side products, with intermittent hydrolysis to mononucleotides in the case of aminoalkyl-poly C, is monitored by reversed-phase high-performance liquid chromatography. Both Dns-DAO-poly C and succinyl-lysozyme-DAO-poly C covalent conjugates are then prepared and similarly characterized, including separation on a size-exclusion diol high-performance liquid chromatography column. The retention of the latter on a wide-pore reversed-phase column seems to be controlled by the protein moiety. PMID- 4030948 TI - General method for the separation of cyanogen bromide digests of proteins by high performance liquid chromatography. Rabbit skeletal troponin I. AB - In this study, we have demonstrated the necessity for a combination of size exclusion, ion-exchange and reversed-phase high-performance liquid-chromatography to resolve completely a protein digest. Our approach minimizes the number of steps, and the column order provides the maximum information about the properties of the fragments. The order is: (1) size-exclusion (Bio-Rad TSK-250 column), (2) strong cation-exchange (Synchropak S300 column), and finally (3) reversed-phase chromatography (Ultrapore C3). It was desirable for the first step of the procedure to be size-exclusion chromatography to produce the least number of fractions. The volatile eluent used in size-exclusion eliminated the need for subsequent sample desalting. Volatile buffers were not necessary for the ion exchange chromatography, since the fractions were both desalted and purified in the final reversed-phase step. All column effluents were compatible with absorbance measurements at 210 nm to provide maximum sensitivity for peptide detection. The results obtained in this study strongly suggest that the combined use of three methods of separation, which utilize different selectivities (size, charge, hydrophobicity), can provide excellent resolving power for peptide separations. We believe this fast, efficient procedure should be generally applicable to other protein digests. PMID- 4030947 TI - Use of reversed-phase and ion-exchange batch extraction in the purification of bovine pituitary peptides. AB - Bovine posterior pituitaries were extracted with an acidic medium designed to maximize solubilization of peptides while precipitating high-molecular-weight protein. The supernatant was then extracted with C18 reversed-phase cartridges to generate a peptide-enriched fraction. Cartridge eluates were subjected to ion exchange extraction, using a batch procedure which fractionated the peptides into basic, acidic, and neutral pools. Amino-terminal fragments of bovine pro opiomelanocortin were found to be resolved into separate pools by this method. The 1 to 49 fragment was eluted in the acidic pool while the 1 to 77 fragment was eluted in the basic pool. The 1 to 77 fragment was purified by reversed-phase high-performance liquid chromatography. Amino acid analysis of the fragments, generated from trypsin and V8 protease digestion of the 1 to 77 fragment, permitted assignment of cystine bridges between residues 2 and 24 and between residues 8 and 20. Results from amino sugar analysis were consistent with the presence of an O-linked oligosaccharide at threonine45 and an N-linked oligosaccharide at asparagine65. PMID- 4030949 TI - Automated tandem high-performance liquid chromatographic system for separation of extremely complex peptide mixtures. AB - We have developed an automated tandem chromatography system, which consists of a combination of ion-exchange column chromatography and reversed-phase column chromatography. The system is composed of two independent high-performance liquid chromatography assemblies, in each of which programmed elution is carried out by a computer-assisted controller. A peptide mixture is applied to an ion-exchange column and is eluted in a stepwise manner. The eluent from the first column is introduced directly into the second, reversed-phase column, which is connected in tandem through a tee tube. After application of two column volumes of the eluent, reversed-phase chromatography is performed by linear gradient elution. Stepwise elution for ion-exchange chromatography and the gradient elution for reversed phase chromatography are synchronized by a computer program. The resolving power and the reproducibility of the method were tested by using a tryptic digest of human ceruloplasmin [molecular weight 132 000 daltons (132 kDa)]. By this method, the digest was resolved reproducibly into several hundred peaks within 16 h. All of the four glycopeptides expected to be obtained by tryptic digestion were purified easily from the whole digest of the protein. Comparison of the peptide maps between a single-chain and a degraded form of ceruloplasmin facilitated the identification of two tryptic peptides, derived from the carboxyl-terminal regions of 67 kDa and 50 kDa fragments of the degraded form, which lack the carboxyl-terminal arginine and lysine residues, respectively. The method may be applicable to comparative peptide mapping of very large proteins exhibiting molecular microheterogeneity, such as carbohydrate or genetic variants; it also can be used complementarily for sequence support of DNA sequencing as well as for preparative purification of peptides as a strategy of protein sequencing of very large proteins. PMID- 4030951 TI - High-performance liquid chromatography of tRNAs on novel stationary phases. AB - Rapid separation of a group of tRNAs was carried out on novel siliceous bonded stationary phases with aqueous eluents by using gradient elution with increasing or decreasing salt gradient, as usual in electrostatic interaction chromatography or hydrophobic interaction chromatography, respectively. The stationary phases consist of microparticulate macroporous silica with surface-bound polar moieties, containing weak cationic and/or hydrophobic binding sites. Depending on the nature of the binding sites, the stationary phases exhibit different retention behavior and selectivity for tRNAs. Aqueous phosphate solutions were used as the eluent, and in many cases isocratic elution was sufficient to separate seven tRNAs. Addition of magnesium ions or n-decylbetaine to the eluent resulted in lower retention, the latter causing a greater increase in the eluent strength. The optimum pH range of the eluent was 5.5-6.5. PMID- 4030950 TI - High-performance hydrophobic-interaction chromatography on ether-bonded phases. Chromatographic characteristics and gradient optimization. AB - This paper is a continuation of the evaluation of hydrophilic ether columns for the separation of proteins by hydrophobic-interaction chromatography. In this approach, linear salt gradients of decreasing concentration of ammonium sulfate yield sharp chromatographic peaks with high mass recovery and maintenance of biological activity. Mild adsorption conditions are indicated by the minimal changes in chromatographic peak area of native proteins as a function of contact time by the biopolymer with the stationary phase. Further evidence of minimal kinetic processes under the chromatographic conditions are seen in the constancy of isocratic retention with mobile phase flow-rate and sample load up to 2 mg. Based on the well-behaved chromatographic characteristics, we have explored gradient optimization in terms of the Snyder model for gradient elution. It is shown that changes in retention, peak capacity and peak height follow predicted gradient time dependencies. Moreover, the influence of particle diameter and column length are found to be in agreement with expected behavior, based on the model. As a consequence of the agreement, prediction of conditions for optimum separation for a particular problem are possible. Other studies examine the influence of specific ion effects, e.g., Mg2+ binding to protein, which can override retention based on predicted surface tension behavior. Some characteristics of the ether column for hydrophobic-interaction chromatography are shown, e.g., column stability at pH 8 and sample capacity. PMID- 4030952 TI - Fourth International Symposium on High-Performance Liquid Chromatography of Proteins, Peptides and Polynucleotides. Part II. Baltimore, MD, December 10-12, 1984. PMID- 4030953 TI - Reversed-phase high-performance liquid chromatographic separation and quantitation of phenylthiohydantoin derivatives of 25 amino acids, including those of cysteic acid, 4-hydroxyproline, methionine sulfone, S carboxymethylcysteine and S-methylcysteine. AB - A high-performance liquid chromatography system is presented which allows separation and quantitation (in the range 4-1000 pmol) of all common phenylthiohydantoin amino acids, including derivatives of 4-hydroxyproline, methionine sulfone and three differently modified forms of cysteine. By showing the actual solvent gradient during elution (as opposed to the programmed gradient) and by supplying information on the effects of minor changes in solvent pH, column temperature, flow-rate, and concentration of 2-propanol in the gradient, we make guidelines available for fine-tuning the separation with new Ultrasphere-ODS (C18) columns. PMID- 4030954 TI - Separation of peptides by strong cation-exchange high-performance liquid chromatography. AB - The effects of pH and gradient conditions on the separation of a series of ten peptides (9-36 residues) and carboxamidomethylated troponin I (CM-TnI, 178 residues) on a new commercially available strong cation-exchange silica based 300 A column (Synchropak S300) were examined. The elution times of the peptides were linear with respect to their net charge at pH 3.0 and pH 6.5. The basic protein CM-TnI (pI approximately 9.5) and peptides with net charges from +2 to +10 were separated with linear AB salt gradients varying from 5 mM to 10 mM B per min (A = 5 mM KH2PO4 buffer, pH 6.5 or 3.0; B = 5 mM KH2PO4 buffer, pH 6.5 or 3.0, containing 1 M KCl). All peptides and CM-TnI were eluted with KCl concentrations below ca. 0.6 M. The advantage of performing cation-exchange chromatography over anion-exchange chromatography was demonstrated for the separation of peptides which, while acidic or weakly basic at neutral pH, through protonation of the acidic functions results in positively charged peptides at pH 3.0. PMID- 4030955 TI - Quantitative affinity high-performance liquid chromatography of neuroendocrine polypeptides using porous and non-porous glass derivatives. AB - Analytical affinity HPLC was developed to isolate and characterize neuroendocrine peptide/protein components. Bovine neurophysin II (NP-II) was covalently immobilized on succinamidopropyl derivatives of both controlled-pore glass (CPG) and non-porous glass (NPG). These derivatives were packed into 25 X 0.46 cm I.D. stainless-steel columns and incorporated into a high-performance liquid chromatograph. Interaction of [3H]Arg8-vasopressin ([3H]AVP) with NP-II was examined by chromatography of AVP on both CPG and NPG affinity matrices. Zonal elution profiles of [3H]AVP on NPG matrix showed, as predicted theoretically, a linear dependence of retardation on the concentration of hormone injected. The data permit calculation of the equilibrium dissociation constant for the NP II/AVP interaction. Elution characteristics also were measured by frontal analysis of large-zone chromatography experiments, the results of which were in good agreement with the zonal elution analysis. Affinity resulting from dimerization also was studied by chromatography of [125I]NP-II on the NPG matrix. In this case, concentration dependence of retardation was non-linear, again as predicted theoretically. Off-rate kinetic constants for dissociation of the mobile interactant from the stationary phase also were obtained. The studies illustrate the utility of analytical affinity HPLC on non-porous beads for measuring relative affinities for various soluble ligands with small amounts of material. Chromatography on the CPG column proved useful for purification of microscale amounts of [3H]AVP. PMID- 4030956 TI - Protein A-coated glass beads. Universal support medium for high-performance immunoaffinity chromatography. AB - High-performance immunoaffinity chromatography (HPIC) is a technique for the fast isolation and quantitation of both antibodies and antigens. Protein A-coated glass beads provide a stable general immobilization support for most immunoglobulin G (IgG) antibodies. In conjunction with the modern expanding repertoire of monoclonal antibodies, HPIC can be applied to the quantitation and isolation of any biological material, in an active form. PMID- 4030957 TI - Isolation of unliganded steroid receptor proteins by high-performance size exclusion chromatography. An investigation of steroid-dependent structural alterations. AB - The physicochemical properties of unliganded steroid receptor proteins remain largely unknown primarily due to receptor lability in the absence of specific ligand, especially during prolonged biochemical analyses. We have utilized high performance size-exclusion chromatography (HPSEC) as a rapid means of investigating the structural properties of cytosolic estrogen receptor proteins in both the presence and absence of [3H]estradiol-17 beta. Cytosols prepared from immature calf uteri were analyzed by HPSEC on an Altex TSK-3000 SW column (600 mm X 7.5 mm I.D.) either before or after incubation with 10 nM [3H]estradiol-17 beta. Postcolumn detection of previously unliganded receptor was accomplished by incubation of fractions (0.38 ml) with 10 nM [3H]estradiol-17 beta for 2-18 h at 0 degrees C. Receptor-bound steroid was separated from free steroid by incubation with small pellets of hydroxylapatite. Nonspecific binding of [3H]estradiol-17 beta in parallel fractions was estimated using an unlabelled competitor (diethylstilbestrol) specific for the estrogen receptor. In low ionic strengths the receptor exists as a single, relatively stable, large form (retention time 34 min). The elution properties of this receptor configuration do not depend on bound steroid ligand. Analysis of receptor at elevated ionic strengths in the presence and absence of steroid ligand suggests that the salt-induced dissociation of receptor components to smaller forms (retention time 47 min) may be partially steroid-dependent. Characterization of receptor in 6 M urea demonstrates the presence of intermediate-sized receptor components (retention time 36-38 min). Analyses of receptor in 6 M urea-0.4 M potassium chloride suggests an inhibition of the more extensive salt-induced dissociation event seen in 0.4 M potassium chloride alone. Furthermore, the intermediate-sized receptor forms seen under these conditions (retention time 41-42 min) are generated in a steroid-dependent manner. The preparation of different molecular forms of biologically active, unliganded estrogen receptor by HPSEC should help further our investigations into the molecular mechanism(s) by which steroid hormones exert their receptor-mediated effects on target cells. PMID- 4030958 TI - High-performance hydrophobic-interaction chromatography of steroid hormone receptors. AB - The use of high-performance hydrophobic-interaction chromatography (HPHIC) on SynChropak 500 propyl columns has been evaluated for the first time in the analysis of estrogen receptors labeled with [125I]iodoestradiol-17 beta. These receptors were extracted from reproductive tissues with 500 mM phosphate buffer and applied to the stationary phase. Utilizing an inverse phosphate gradient (500 to 10 mM), elution resulted in rapidly excluded components in the void volume followed by a second radioactive peak at 400 mM phosphate. Both peaks appeared to contain specific estrogen-binding components in that steroid association was inhibited by diethylstilbestrol and free ligand was eluted with a different retention time. A great deal of [125I]iodoestradiol-17 beta was retained by the column. Inclusion of acetonitrile (20%) in the mobile phase resulted in the elution of [125I]iodoestradiol-receptor complexes at a different position from free ligand. Distribution of specific estrogen-binding components appeared to be tumor-dependent. These preliminary results indicate that HPHIC may be useful for isolating various isoforms of steroid hormone receptors so that detailed information regarding their intrinsic properties may be ascertained. PMID- 4030959 TI - Improved method for the determination of N-acetylcysteine in human plasma by high performance liquid chromatography. AB - An improved method for the determination of N-acetylcysteine by paired-ion reversed-phase high-performance liquid chromatography has been developed. Following incubation with dithiothreitol to release bound N-acetylcysteine, free N-acetylcysteine and the internal standard N-acetylpenicillamine were derivatised with 2,4-dinitro-1-fluorobenzene. The samples were then deproteinised by ultrafiltration. The dinitrophenyl derivatives were extracted from acidified ultrafiltrate into diethyl ether and purified by using a back-extraction step. They were then separated from naturally occurring plasma components and reagent impurities by high-performance liquid chromatography, utilising an Ultrasphere ODS (5 microns) reversed-phase column and detection at 360 nm. PMID- 4030960 TI - Methods for chromatofocusing of cerebrospinal fluid and serum immunoglobulin G. AB - Chromatofocusing programs were designed for separations of submilligram amounts of normal and abnormal human IgG. The Pharmacia FPLC system, equipped with a Mono P column or a specially designed, small column was used for the separations. Normal IgG in paired cerebrospinal fluid and serum samples, paired samples from patients with intrathecal immunoglobulin G synthesis, as well as sera with IgG M components were examined. Abnormal immunoglobulin G components, especially those with pI values greater than ca. 7.0 pH units, were easily identified. PMID- 4030961 TI - Application of a new ion exchanger TSK-GEL DEAE-5PW, to the purification of Cu,Zn superoxide dismutase of bovine erythrocytes. AB - We have developed an effective method for the purification of Cu,Zn-super-oxide dismutase [E.C. 1.15.1.1] from bovine erythrocytes. This enzyme functions as a scavenger of superoxide radical, and it seems to be a key enzyme in the metabolism of active oxygen species. Application of this enzyme as a drug has been considered, and for this purpose a highly purified preparation is necessary. The first purification of this enzyme was reported by McCord and Fridovich [J. Biol. Chem., 244 (1969) 6049]. The limiting step in their method is the removal of the small amount of contaminating protein from the acetone-precipitated crude preparation (3000 units/mg protein). We found that a new, high-performance ion exchanger, TSK-GEL DEAE-5PW, improves this step and makes possible the large scale preparation of pure protein. Optimal conditions for a TSK-GEL DEAE-5PW preparative column (150 X 21.5 mm I.D.) were established. The acetone precipitated crude enzyme was dissolved in 20 mM Tris-HC1 buffer (pH 7.5), protein concentration 11.0 mg/ml, applied to the column, and eluted with a linear gradient of sodium chloride from 0 to 0.3 M. The flow-rate and sample volume were set to 4.0 ml/min and 8.0 ml, respectively. Under these conditions, the fractionated Cu,Zn-superoxide dismutase showed a single band on sodium dodecyl sulfate-polyacrylamide gel electrophoresis and ion exchange high-performance liquid chromatography, and a specific activity of 3800 units/mg protein. The recovery of activity was 75%, and the cycle time was 120 min. A yield of 80-85 mg of purified enzyme was obtained per cycle. The preparation thus isolated has the highest purity and activity so far reported. We conclude that TSK-GEL DEAE-5PW is the practical choice for large-scale purification of Cu,Zn-superoxide dismutase. PMID- 4030962 TI - Determination of the dissociation constant of oligomeric proteins by size exclusion high-performance liquid chromatography: application to human haemoglobin. AB - The measurement of protein retention volumes on a size-exclusion chromatographic column offers the possibility of determining dissociation constants for oligomeric proteins, as changes in the retention volume, depending on the concentration of the protein, are due to a dissociation equilibrium. The retention volume may be calibrated in terms of dissociation constant by using either extreme concentration conditions or chemical modifications that shift the equilibrium towards a single species. When zonal chromatography is used, the dilution during elution modifies the equilibrium state. In contrast, the saturation method permits the concentrations of the different species to be kept constant. These two methods were compared and the elution factor that must be used in zonal chromatography on high-performance size-exclusion columns (LiChrospher Diol) was obtained. The tetramer-dimer dissociation constants of normal and modified haemoglobins were measured by this method, and the results are in accordance with flash photolysis measurements. PMID- 4030963 TI - Comparison of reversed-phase and cation-exchange high-performance liquid chromatography for separating closely related peptides: separation of Asp76-human parathyroid hormone (1-84) from Asn76-human parathyroid hormone (1-84). AB - Cation-exchange high-performance liquid chromatography (CE-HPLC) was compared with ordinary reversed-phase high-performance liquid chromatography (RP-HPLC) for separating closely related peptides. Some synthetic samples of bradykinin and angiotensins, which were homogeneous according to RP-HPLC, were found to be inhomogeneous when analyzed by CE-HPLC. On the other hand, diastereomeric peptides could be separated much more efficiently by RP-HPLC than by CE-HPLC. These results indicated that the purity of synthetic peptides should be checked not only by RP-HPLC but also by ion-exchange HPLC. In the case of human parathyroid hormone (hPTH), baseline separation of Asp76-hPTH from Asn76-hPTH by RP-HPLC was not possible, but was by CE-HPLC. Using this method we confirmed that the Asn residue in hPTH at position 76 could not be converted into the Asp residue under the conditions used to isolate and purify it from human organs. PMID- 4030964 TI - Interaction between fluorescence-labeled fibronectin fragments studied by gel high-performance liquid chromatography. AB - Fibronectin is a large, adhesive glycoprotein which self-associates on many cell surfaces. We have begun to study this reaction by determining the domains of fibronectin which interact with each other. To avoid possible solid-phase artifacts of affinity chromatography, we have devised a solution-phase assay in which the smallest fibronectin fragment is labeled with fluorescamine, mixed with unlabeled fibronectin, and complexation is observed by the appearance of a new higher-molecular-weight peak on gel high-performance liquid chromatography columns. The assay allowed use of excess unlabeled reactant, high-sensitivity, low background without removal of reagent, and fast analysis. Our results show that the amino- and carboxyl-terminal fibronectin fragments bind the native molecule in solution. PMID- 4030965 TI - Characterization of the subunit structure of dopamine beta-hydroxylase by anion exchange high-performance liquid chromatography. PMID- 4030966 TI - Analysis of different forms of recombinant human leukocyte interferons and synthetic fragments by high-performance liquid chromatography. AB - Analytical high-performance liquid chromatography (HPLC) conditions are reported for the evaluation of recombinant human interferon monomers: recombinant human leukocyte interferon A (rIFN-alpha A), rIFN-alpha D, and the hybrid rIFN-alpha A1 62/D64-166. The two monomeric forms of rIFN-alpha A (slow-migrating monomer and fast-migrating monomer) were also resolved by HPLC. Conditions are reported for the HPLC separation of oligomers (dimers and trimers) of rIFN-alpha A. The synthesis and analytical HPLC of the carboxy-terminus fragment, corresponding to IFN-alpha D (140-166), and a series of analogues comprising the IFN-alpha A (105 125) region is reported. The syntheses were accomplished by the solid-phase peptide synthesis procedure and the products were purified by preparative HPLC. PMID- 4030967 TI - Rapid, high-resolution procedure for assessment of estrogen receptor heterogeneity in clinical samples. AB - Approximately two-third of the women with breast cancer may benefit from hormone therapies if the lesion contains estrogen receptor in reasonable levels (greater than 10 fmol/mg cytosol protein). Our lab and others have suggested that not only the concentration, but the various molecular form(s) of the receptor may be an important factor in predicting patient responsiveness. Until now, this heterogeneity has been determined by analysis on sucrose density gradients requiring 16 h of centrifugation. Other methodologies which can disclose the profile of receptor isoforms are compromised by irreproducibility, poor recovery, or the length of time required to perform the analysis. We believe that high performance liquid chromatography (HPLC) in the anion-exchange and chromatofocusing modes may be able to supply more insight into receptor structure than currently available by any other method. Utilizing the high activity ligand [16 alpha-125I]iodoestradiol-17 beta (2200 Ci/mmol) and flow-through equipment to monitor conductivity, pH, and radioactivity, we are able to describe the distribution of ionic isoforms in crude cytosolic preparations of breast cancer and uterus. This "on-line" technology is rapid (chromatogram is complete within 120 min), sensitive (receptor isoforms equivalent to 1 fmol are apparent), efficient (columns typically return greater than 90% of applied radio-labeled receptor) and reproducible (due to the sophistication of modern HPLC equipment). It is clear these techniques may be used in the clinical setting to better describe the profile of estrogen receptor isoforms and should be explored as a method of correlating receptor structure with hormone function in responsive tissues. PMID- 4030969 TI - Analysis of anthralin in dermatological products by reversed-phase high performance liquid chromatography. AB - A reversed-phase liquid chromatographic method is described for the determination of anthralin in topical products. The factors affecting the degradation of anthralin solid and solutions are discussed. Ultraviolet spectra of degradation products are presented. The assay method has been thoroughly optimized and is shown to be specific, precise, and accurate. PMID- 4030968 TI - [Affinity electrophoresis in polyacrylamide gel. Influence of the concentration in the gel on the apparent affinity of cholinesterase for an anionic ligand site]. AB - Affinity electrophoresis of three purified molecular forms of human plasma cholinesterase (monomer C1, dimer C3, tetramer C4) was carried out in polyacrylamide gels at various total acrylamide concentrations ranging from 3.48 to 9% in a discontinuous buffer system. A water-soluble linear copolymer supporting procainamide, a ligand of the anionic site of cholinesterase, was physically entrapped at various concentrations within the gel network. The combined effects of gel concentration and ligand concentration on the affinity pattern of the three molecular forms were studied. It was found that gel concentration influences the apparent binding activity of their anionic site: The apparent strength of interaction varied with the gel concentration: the denser the gel was, the higher the apparent affinity. The ligand-induced isomerization process was also depending on the gel concentration: the ligand concentration from which each zone is splitting into two moving zones decreased as the total gel concentration increased. These results show that the electrophoretic matrix plays an important role in the affinity process in affinity electrophoresis presumably by controlling kinetic effects: kinetics of protein-ligand complex formation and dissociation reactions, and mass transfer kinetics. PMID- 4030970 TI - Separation of basic, hydrophilic peptides by reversed-phase ion-pair chromatography. IV. Preparative applications related to purification of two substrates of cyclic AMP-dependent protein kinase. PMID- 4030971 TI - Heterogeneity of alkaline phosphatase observed by high-performance liquid chromatography. PMID- 4030972 TI - Rapid extraction and purification of diethylstilboestrol in bovine urine hydrolysates using reversed-phase C18 columns before determination by radioimmunoassay. PMID- 4030974 TI - Aqueous size-exclusion analysis of Parietaria pollen extracts. PMID- 4030973 TI - Stabilization of 5-methyltetrahydrofolic acid and subsequent analysis by reversed phase high-performance liquid chromatography. PMID- 4030975 TI - Determination of sterol and triterpene alcohol acetates in natural products by reversed-phase liquid chromatography and gas chromatography-mass spectrometry. AB - A partial separation of nine sterol acetates and seven triterpene alcohol acetates by reversed-phase liquid chromatography is described. Good results are obtained using acetonitrile-water (90:10, v/v) as mobile phase with an UV detector at 205 nm. The variation in sterol sensitivity shows that this technique is not suitable for quantitative analyses. A combination of this technique for the fractionation of the natural sterol mixture, gas-liquid chromatography for quantitation and gas chromatography-mass spectrometry for identification is necessary for the determination of sterol compounds contained in natural products. An example of the separation, identification and quantitation of sterol acetates from sunflower seed oil is given. PMID- 4030976 TI - Quantitative analysis of phylloquinone (vitamin K1) in soy bean oils by high performance liquid chromatography. AB - A high-performance liquid chromatographic method for determining phylloquinone (vitamin K1) in soy bean oils is described. Resolution of vitamin K1 from interfering peaks of the matrix was obtained after enzymatic digestion, extraction and liquid-solid chromatography on alumina. An isocratic reversed phase chromatography with UV detection was used in the final stage. The quantitation was carried out by the standard addition method, and the recovery of the whole procedure was 88.2%. PMID- 4030977 TI - 1-DOPA decarboxylase and dopamine-beta-hydroxylase isolated from sympathetic splenic nerves estimated by sodium dodecyl sulphate polyacrylamide gel electrophoresis with and without mercaptoethanol. PMID- 4030978 TI - Quantitative determination of betamethasone and its major metabolite in equine urine by micro-liquid chromatography-mass spectrometry. AB - Micro-liquid chromatography-mass spectrometry (micro-LC-MS) was utilized to quantitatively determine betamethasone and its major unconjugated metabolite, 6 beta-hydroxybetamethasone, in equine plasma and urine. The advantage of micro-LC MS over conventional gas chromatography-mass spectrometry in corticosteroid determination is illustrated and the reliable, steadfast nature of micro-LC-MS is demonstrated through example. PMID- 4030979 TI - Determination of oestriol in pregnancy urine by normal-phase high-performance liquid chromatography with electrochemical detection. AB - A method for the determination of oestriol in pregnancy urine by normal-phase high-performance liquid chromatography with electrochemical detection is described. A large-volume wall-jet cell with an Ag-Ag+ reference electrode was used as the detector system. The limit of detection obtained is comparable to that of electrochemical detection following reversed-phase liquid chromatography. One of the advantages of electrochemical detection with normal-phase systems is that adsorption problems are minimized. PMID- 4030980 TI - Determination of the serum concentration of spironolactone and its metabolites by high-performance liquid chromatography. AB - A simple and rapid high-performance liquid chromatographic assay is described for the simultaneous determination in serum of the aldosterone antagonist spironolactone and its metabolites 7 alpha-thiomethylspirolactone, 6 beta-hydroxy 7 alpha-thiomethylspirolactone and canrenone. Ultraviolet absorption at 240 nm was used to detect the different compounds after elution on a normal-phase column. Endogenous serum substances did not interfere with the assay. This method provides a convenient tool in pharmacokinetic studies of spironolactone, in contrast to previously reported aspecific fluorimetric assays or time-consuming thin-layer chromatographic analyses of radioactive biological material. PMID- 4030981 TI - Derivatization in aqueous solution, isolation and separation of tetrahydro-beta carbolines and their precursors by liquid chromatography. AB - Derivatization of indole ethylamines and 1,2,3,4-tetrahydro-beta-carbolines in aqueous solution with methyl chloroformate has been used to facilitate the isolation of these compounds. The initial derivatization eliminated the potential for the artifactual formation of these compounds via the condensation of the indole ethylamine with an aldehyde or alpha-keto acid during the work-up procedure. The derivatized compounds possessed improved chromatographic properties which allowed for their facile separation by reversed-phase liquid chromatography and their fluorescent detection at the nanogram level. PMID- 4030982 TI - Determination of diclofensine, an antidepressant agent, and its major metabolites in human plasma by high-performance liquid chromatography with fluorometric detection. AB - A sensitive and selective high-performance liquid chromatographic assay was developed for the determination of diclofensine (I) and its key metabolites in human plasma. The assay involves deproteinization of plasma, overnight Glusulase incubation to hydrolyze the major metabolite (I-B-glucuronide), extraction of the parent compound and its deconjugated metabolites (I-A, I-B and I-C) from the alkalinized aqueous phase into diethyl ether-ethanol (95:5), the residue of which (containing compounds I, I-A, I-B and I-C) is alkylated with 2-iodopropane dissolved in acetone, using solid potassium hydroxide as a catalyst. The compounds are extracted from the reaction mixture into diethyl ether, after adding ethanol-water-acetic acid (55:40:5), the residue of which is dissolved in 0.05 M sulfuric acid, and reacted with mercuric acetate at 100 degrees C, which oxidizes tertiary tetrahydroisoquinolines to their 3,4-dihydroisoquinoline derivatives, followed by a photochemical reaction in the same solution to form intensely fluorescent isoquinolinium derivatives. An aliquot of this reaction mixture is injected onto a reversed-phase high-performance liquid chromatography column (5-microns Nova-Pac C13 phase in a radial compression cartridge, 10 cm X 8 mm), using the mobile phase 0.25 M triethylammonium phosphate (pH 2.5)-0.25 M acetic acid-methanol-acetonitrile-tetrahydrofuran (150:350:125:375:25). The void volume (Vo) is approximately 1.4 min and the retention times (tR) of the respective isoquinolium derivatives of diclofensine (I) are ca. 3.5 min, internal standard (II) ca. 4.2 min, nordiclofensine (I-A) ca. 5 min, while the phenolic metabolites I-B and I-C give peaks at 6.4 min and 10.4 min, respectively. The derivatives are detected by fluorescence. The method was used to determine plasma concentrations of the parent drug (I) and its major phenolic metabolite I-B (aglycone) in plasma in two normal volunteers following a single oral 45-mg dose and following seven consecutive days of oral dosing of 45 mg three times a day as part of a multiple ascending dose tolerance study. PMID- 4030983 TI - Selective and sensitive high-performance liquid chromatographic assay for the metabolites of nomifensine in human plasma. AB - A selective high-performance liquid chromatographic method for the determination of the three metabolites of nomifensine in human plasma is described. All metabolites and the internal standard, mexiletine, are extracted with diethyl ether and then back-extracted into an acidic aqueous phase. After subsequent extraction into diethyl ether the metabolites are analysed by high-performance liquid chromatography. A reversed-phase C18 column is used with a mobile phase of dioxane-methanol-potassium phosphate buffer (pH 2.25). The sensitivity of the method is 0.007 micromol/l for all metabolites. Extraction efficiencies are 84.6%, 75.8%, and 78.2% for 4'-hydroxynomifensine, 4'-hydroxy-3' methoxynomifensine and 3'-hydroxy-4'-methoxynomifensine, respectively. The reproducibility of the method is good, the coefficients of variation (%) varying between 2.1% and 9.9% in the concentration range 0.05-1.00 micromol/l. The procedure was applied to human plasma samples from a volunteer who had received a single oral dose of nomifensine. The method is accurate and sensitive for pharmacokinetic studies on the metabolites of nomifensine. PMID- 4030984 TI - Determination of nifedipine in human plasma by high-performance liquid chromatography with electrochemical detection. AB - A rapid, accurate and sensitive high-performance liquid chromatographic assay was developed for the determination of nifedipine in human plasma. A toluene extract of an alkalinized plasma sample was chromatographed on a reversed-phase column with electrochemical detection at +0.95 V. The recovery of nifedipine from plasma was about 100%. The detection limit for nifedipine in plasma was 2 ng/ml using 0.5 ml of sample. The assay gave a linear response over the concentration range 5 400 ng/ml in plasma. The coefficients of variation from 9.6 to 191.0 ng/ml varied between 5.2 to 1.0% and the accuracy did not exceed 3.0%. Photodegradation products and metabolites of nifedipine did not interfere in the analysis. This method allowed the behaviour of nifedipine in humans to be studied. PMID- 4030985 TI - Isolation and analysis of N-oxide metabolites of tertiary amines: quantitation of nicotine-1'-N-oxide formation in mice. AB - To investigate the formation and elimination of nicotine-1'-N-oxide (NNO) in mice treated with a single injection of nicotine, sensitive and selective methods were developed to quantitate this polar and heat-labile metabolite. The compound was isolated from tissue homogenates as a dodecyl sulfate ion pair with C18 extraction cartridges and analyzed on an amino bonded-phase high-performance liquid chromatographic column with a mobile phase consisting of isopropanol water. Overall recoveries of NNO were 64-76% from biological media. Several methods of detection were evaluated; radiolabeling was necessary to achieve the sensitivity required for pharmacokinetic studies in mice. The cis and trans isomers of NNO were separated on a Partisil PAC column and enzymatic selectivity was evaluated for the formation of these isomers in mice. PMID- 4030987 TI - Liquid chromatographic analysis of clonazepam in human serum with solid-phase (Bond-Elut) extraction. AB - A simple, sensitive, selective and precise liquid-column chromatographic assay for clonazepam is described, in which 1 ml of serum containing 50 micrograms/l methylclonazepam as an internal standard is extracted by elution from a Bond-Elut column with 400 microliter of methanol. An aliquot of the eluate is injected on to a reversed-phase column and eluted with a mobile phase of acetonitrile- phosphate buffer (30:70) at a flow-rate of 2 ml/min at a column temperature of 50 degrees C. Detection is at 254 nm. Chromatography is complete in 12 min. A sensitivity of 2 ng/ml is attained when 1 ml of serum is extracted. Analytical recovery of the clonazepam added to serum ranged from 91% to 99% with a coefficient of variation of 6.0%. This assay for clonazepam has good precision, with coefficients of variation of 11% at 15 ng/ml and 2.6% at 50 ng/ml. There was no interference from any of the commonly used antiepileptics. PMID- 4030986 TI - Sensitive liquid chromatographic method for physostigmine in biological fluids using dual-electrode electrochemical detection. AB - A liquid chromatographic method using dual-electrode detection has been developed for determination of physostigmine in biological fluids. The limit of detection is in the order of 25-50 pg mol-1 of plasma. A high sample throughput is obtained by a single solvent extraction step and autoinjection into the chromatograph. Data following oral doses of physostigmine are presented. PMID- 4030988 TI - [Determination of sulpiride and sultopride by high-performance liquid chromatography for pharmacokinetic studies]. AB - A high-performance liquid chromatographic method with UV detection (226 nm) for the analysis of sulpiride and sultopride in body fluids has been developed. Plasma, red blood cell (RBC) and urine samples were extracted by chloroform at pH 10. Internal standards were a new substituted benzamide (N-[(ethyl-1-pyrrolidinyl 2)methyl] methoxy-2-ethylsulphonyl-5-benzamide, DAN) for the sulpiride assay and sulpiride for the sultopride assay. The detection limit in plasma and RBC was 10 ng/ml for sulpiride and 15 ng/ml for sultopride. The proposed techniques were selective, reliable and sensitive enough to be used for pharmacokinetic studies and drug monitoring. Some plasma and RBC data from pharmacokinetic studies in healthy volunteers (sulpiride) or patients (sultopride) are presented. Half-lives determined from either plasma or RBC concentrations were similar (7 h for sulpiride and 5 h for sultopride). PMID- 4030990 TI - Determination of serotonin in plasma by liquid chromatography with electrochemical detection. PMID- 4030989 TI - Method for the determination of 4'-deoxydoxorubicin, 4'-deoxydoxorubicinol and their 7-deoxyaglycones in human serum by high-performance liquid chromatography. AB - 4'-Deoxydoxorubicin (4'-DOX) is a new and structurally similar analogue of the anti-cancer drug adriamycin (ADR). Based on known pathways of metabolism of ADR a high-performance liquid chromatographic method for the separation and identification of 4'-DOX and five possible metabolites was developed. Sensitivity for serum is 10 ng/ml for 4'-DOX and its alcoholic product 4'-deoxydoxorubicinol (4'-DOL) and 2 ng/ml for four of its aglycone products with coefficients of variation in k' of less than 5% throughout the day. An extraction step with better than 80% recovery of 4'-DOX and five reference metabolites from serum is described. Analysis of patient sera identified two metabolite peaks. These co eluted with the reference metabolites of 4'-DOL and the 7-deoxyaglycone of 4' DOX. Pharmacokinetics of the parent drug followed a two-compartment model. Both the metabolites were produced quickly and disappeared quickly. PMID- 4030991 TI - Determination of meprobamate as an n-butylboronate ester derivative in serum by gas-liquid chromatography. PMID- 4030992 TI - Determination of gabapentin in plasma and urine by high-performance liquid chromatography and pre-column labelling for ultraviolet detection. PMID- 4030993 TI - Use of ELISA for measuring the extent of serological cross-reactivity between plant viruses. AB - The degree of antigenic relatedness between two plant viruses is commonly expressed by a serological differentiation index (SDI) which corresponds to the average number of two-fold dilution steps separating homologous from heterologous precipitin titers. Results obtained with several tobamo- and tombusviruses indicated that the indirect form of the enzyme-linked immunosorbent assay (ELISA) can also be used for calculating SDI values. This was achieved by comparing the antiserum dilutions that lead to the same absorbance measurements (for instance 1.0) when homologous and heterologous viruses are assayed by ELISA. SDI values calculated from ELISA were similar to those obtained from precipitin tests. Because of its greater sensitivity, ELISA is able to quantify weak cross reactions that are not detectable by precipitin tests. PMID- 4030994 TI - Rapid purification of HBsAg from human plasma. AB - A method is described for the rapid isolation of purified HBsAg from infected donor plasma. This method uses polyethylene glycol precipitation and a single isopycnic ultracentrifugation step in which the gradient is formed in situ. It works equally well using a small swingout rotor or a zonal rotor. PMID- 4030995 TI - Detection of both hepatitis B e antigen and antibody in a single assay using monoclonal reagents. AB - Monoclonal antibodies raised against HBeAg were used to develop a HBeAg and anti HBe detection assay. Monoclones containing anti-HBe were used both for the coating of the solid phase and for the fluid phase label in a sandwich type assay. The percentage binding of 125I-labelled anti-HBe to serum HBeAg was much greater than that seen in a similar assay using only polyclonal reagents. Therefore it was possible to add a small quantity of HBeAg for neutralising any anti-HBe present in a test serum without affecting HBeAg detection. This small amount of serum HBeAg was incorporated into each test sample thus allowing the determination of the e status of a patient using only one aliquot of test serum. This single test assay could be performed either as a radioimmunoassay or as an ELISA. The sensitivity of these assays was found to be greater than the conventional polyclonal assay particularly with regard to sera containing anti HBe. PMID- 4030996 TI - Assessment of specific virus infectivity and virus neutralization by a progeny virus immunotitration method as exemplified in an adenovirus system. AB - An alternative method for the determination of specific virus infectivity and quantitative measurement of inhibitory activity of antibodies was developed using an adenovirus system. HeLa cells in 37 ml suspension cultures of 1.5 X 10(7) cells were infected with purified adenovirus 2 (Ad2) at different multiplicities of infection. After appropriate incubations, total progeny virus was isolated by a one-step CsCl gradient sedimentation procedure. Recovered virions were disrupted in the presence of 5 M urea and directly quantitated by rocket immunoelectrophoresis against an anti-hexon-antiserum. One infectious unit (IU) was defined as the lowest amount of virions capable of producing maximum yield of progeny virus in the standardized system, and corresponded to 32 physical particles, which also equalled one plaque-forming unit (pfu). The coefficient of the inter-experimental variation of the total virus yield determination was 13%. Reduction in progeny virus synthesis was taken as a measurement of the degree of the inhibitory effect of neutralizing antibodies. A linear relationship was obtained between dilution of a neutralizing antiserum and reduction in synthesis of progeny virus. Separate determinations of such neutralization revealed a coefficient of variation of 5.5%. PMID- 4030997 TI - Thermal inactivation of Pichinde virus. AB - Detailed information regarding the kinetics of thermal inactivation of Pichinde, an arenavirus, is presented. Inactivation of virus infectivity proceeded as a first order reaction over the temperature range 22-53 degrees C. The determined inactivation rates analysed as a function of absolute temperature revealed that two different reactions were involved. Below 37 degrees C, the energy of activation was determined to be compatible with RNA degradation, whereas at higher temperatures a correspondingly greater value suggests that protein inactivation contributes significantly to loss of infectivity. Both inactivation reactions were retarded in the presence of foetal calf serum to a final concentration of 1%. The relatively short half-life of 12-24 h at 22 degrees C suggests transmission in nature via contaminated foodstuffs and soil may be inefficient. PMID- 4030998 TI - Obesity and caloric intake: the National Health and Nutrition Examination Survey of 1971-1975 (HANES I). AB - Most published studies have failed to show a greater food intake in obese subjects than in nonobese. However, the sample sizes in most of these studies are small and the methodologies open to question. HANES I is based on a probability sample of 20,749 people, representative of the civilian noninstitutional population of the U.S. We analyzed a subsample of 6219 nonpregnant adults whose diet was not influenced by illness or drugs and who stated that their intake, estimated by dietary interview, represented their usual pattern. Neither the caloric intake nor the caloric intake adjusted for physical activity level and age was higher in the obese subjects. This suggests that, unless estimates of food intake differ in accuracy between obese and nonobese subjects, factors other than overeating should be given increased consideration in the etiology of obesity. PMID- 4030999 TI - An analysis of physicians' reasons for prescribing long-term digitalis therapy in outpatients. AB - We examined by medical-record review why long-term digitalis therapy was prescribed in 150 outpatients, the reasons were: supraventricular tachyarrhythmias (35): supraventricular tachyarrhythmias and heart failure (33); and heart failure with sinus rhythm (82). In the patients without supraventricular tachyarrhythmias we scrutinized the diagnosis of heart failure using a clinicoradiographic scoring system and found the diagnosis unlikely in 32 patients. When these 32 patients are combined with the 31 patients who had only one occurrence of supraventricular tachyarrhythmias or heart failure, 42% of the patients were on long-term digitalis therapy for a questionable reason. We conclude that a substantial fraction of general medical outpatients might benefit from digitalis withdrawal, if evidence for heart failure is lacking or if the reason prompting digitalis therapy is isolated to the distant past. PMID- 4031000 TI - Prognosis for women with different symptoms and signs suggesting ischaemic heart disease--a 12-year follow-up. The population study of women in Gothenburg, Sweden. AB - A longitudinal population study of a total of 1462 women aged 38-60 was carried out in 1968-69 in Gothenburg, Sweden. The women have been re-studied in 1974-75 and 1980-81. The incidences of myocardial infarction during the following 12-year period were: three of 29 women with a history of angina pectoris (10%), four of 23 women with initial ECG changes at rest (17%) and one of 30 with ECG changes during work (3%). In addition, all women of similar age in Gothenburg with myocardial infarction during the years 1968-70 have been followed-up with respect to mortality, and in all there were 47 women who were alive on arrival at hospital. The figures for the 12-year overall mortality in the population study were: three women with angina pectoris (10%), four women with ECG changes at rest (17%) and three women with ECG changes during work (10%) and in the series of women with myocardial infarction 21 of 47 (45%). It seemed that the mortality among women with a history of angina pectoris or ECG changes at rest or during exercise indicating ischaemic heart disease was only slightly increased, if at all, compared to other women in the population, while having had a myocardial infarction significantly increased the mortality risk. PMID- 4031001 TI - Detecting effect modification due to the variables controlled in multiple matching. AB - A new approach is presented to the study of heterogeneity of the odds ratio in a case-control design when the possible interaction effects are associated with the variables used for multiple matching. This analysis does not require stratification on the matching covariates. PMID- 4031002 TI - Early diastolic posterior aortic root slope, a clinical guide to the severity of mitral stenosis. AB - This report tests the hypothesis that, in early diastole, motion of the anterior left atrial wall corresponds to the motion that can be observed in the contiguous posterior wall of the aortic root. To test this hypothesis, we examined the effects of mitral stenosis, exercise in normals, exercise induced left ventricular ischemia, left ventricular hypertrophy and left ventricular dysfunction on this slope. Each altered early diastolic atrioventricular interaction as predicted and therefore, the early diastolic motion of the anterior left atrial wall does appear to be mirrored by the early diastolic slope of the posterior wall of the aortic root. Consequently, if interpreted in the clinical context, measurement of early diastolic slope of the posterior wall of the aortic root may serve as a useful guide to separate patients with severe from those with mild mitral stenosis. PMID- 4031003 TI - Multiple tumor incidence in patients with rheumatoid arthritis or allied disorders. AB - The incidence of multiple malignant neoplasms in 55,279 patients with rheumatoid arthritis (RA) or allied disorders was studied by linking two separate nationwide data registers covering the whole Finnish population. The linking of the Social Insurance Institution's Population Register and the Finnish Cancer Registry resulted in 2106 cancer patients in whom both cancer (diagnosed in 1967-1978) and rheumatoid arthritis or allied disorders (diagnosed before cancer) were diagnosed. In 1974, the allied disorders (ankylosing spondylitis or systemic connective tissue diseases) accounted for 3.9% of all the diagnoses in the Social Insurance Institution's Population Register. The incidence of multiple neoplasms was slightly but not significantly higher in cancer patients with RA or allied disorders than in the general population or in all cancer patients taken together. The risk of leukemia was four times higher in the rheumatoid or allied disease cancer patients than in all the cancer patients. The results are consistent with previous results showing that the leukemia incidence in RA patients is higher than expected. PMID- 4031004 TI - Children's type A interview: interrater, test-retest reliability, and interviewer effect. AB - The Miami Structured Interview--1 was developed to assess Type A behavior in preadolescents and adolescents in the United States and Greece. This report describes the interrater and test-retest reliability of the Miami Structured Interview--1, and the effect of different interviewers on the assessment process. Interrater agreements on the A vs not A scale were 73% for Greek American (k = 0.49, p less than 0.01, n = 88), 80% for Mixed American (k = 0.61, p less than 0.01, n = 69), and 88% for Native Greek interviews (k = 0.76, p less than 0.01, n = 65). Exact agreements on a five-point scale were 48% (weighted k = 0.73, p less than 0.01), 42% (weighted k = 0.70, p less than 0.01), and 48% (weighted k = 0.80, p less than 0.01), respectively. Although levels of agreement were all greater than chance, rater bias was observed. Test-retest administrations within 10 min showed 91% agreement (k = 0.82, p less than 0.01) on the A vs not A scale. Analyses suggest interviewers can affect the assessment of Type A behavior. These findings indicate the Miami Structured Interview--1 can (1) reach acceptable levels of interrater reliability, (2) is susceptible to rater bias, (3) has sufficient test-retest reliability for use in longitudinal studies, and (4) must be presented in a standardized way before ratings from interviews conducted by different interviewers can be combined or compared. The strengths and limitations of the Miami Structured Interview-1 are discussed. PMID- 4031005 TI - Cross-cultural validity of the Miami Structured Interview--1 for type A in children: the American-Hellenic Heart Study. AB - The Miami Structured Interview--1 was developed (1) to assess Type A behaviour in a broader age range of children than tested with previous interviews, and (2) for cross-cultural studies. This study examined the validity of the Miami Structured Interview--1 for assessing Type A behavior in 507 American and Greek preadolescent (ages 7-11) and adolescent (ages 12-16) boys. The interview was scored on voice stylistics such as speed of speech, word emphasis, and latency of response. Validity was tested using the Matthews Youth Test for Health (MYTH), a teacher rating scale of Type A behaviors. Interview determined Type A's received significantly higher MYTH scores than non Type A's for American adolescents (p less than 0.05), Greek preadolescents (p less than 0.01), and Greek adolescents (p less than 0.05). The interview also identified extreme groups of Type A's and Type B's for American adolescents (p less than 0.01) and Greek preadolescents (p less than 0.05). The findings support the cross-cultural validity of the Miami Structured Interview--1 and the Type A construct for children. Limitations of the Miami Structured Interview--1 are discussed. PMID- 4031006 TI - Consideration of covariates and stratification in sample size determination for survival time studies. AB - Sample size determination for survival time studies is discussed, taking into account stratification. We present formulas and tables which also apply in the case of multicenter clinical trials. In addition, the same method is used to estimate the sample size requirement when a covariate is grouped into strata. Simulation studies compare the results to covariate adjustment by the Cox proportional hazards model. PMID- 4031007 TI - Glucocorticoid effects on somatomedins and somatomedin inhibitors. AB - Glucocorticoid excess may be associated with poor growth despite normal levels of GH and adequate nutrition. Steroid-induced growth failure could be mediated by defective generation and/or action of somatomedins. To probe potential mechanisms, we examined the effect of corticosteroid administration on net somatomedin activity, immunoreactive somatomedin-C, and separated biologically active somatomedins and somatomedin inhibitors. Twelve children receiving alternate day steroid therapy had circulating somatomedin activity measured by porcine cartilage bioassay. Somatomedin activity fell 6 h after steroids [from 1.02 +/- 0.09 (+/- SEM) to 0.35 +/- 0.07 U/ml; P less than 0.001] and then rose toward normal. No significant change in somatomedin activity occurred during the day off therapy. Further studies were conducted in normal subjects given a single 60-mg dose of prednisone. Six hours after prednisone, somatomedin activity (rat cartilage bioassay) decreased by 46% (P less than 0.01), yet somatomedin-C did not change. To pursue this discrepancy, serum was fractionated on Sephadex G-50, pH 2.4, and separated somatomedin and somatomedin inhibitory bioactivity was measured. Biologically active somatomedins (Kav, 0.50-0.63) were comparable before and after prednisone treatment, as was inhibitory activity found at Kav 0.13-0.25. In contrast, somatomedin inhibitory activity at Kav 0.25-0.38 doubled (111 +/- 8% inhibition of somatomedin action vs. 54 +/- 11%; P less than 0.005) after prednisone therapy. The somatomedin inhibitor in these fractions blunted serum stimulation of sulfate, thymidine, and uridine uptake by test cartilage. These inhibitory effects could not be attributed to direct steroid action, as levels were less than 2 micrograms/dl in inhibitory fractions and addition of cortisol and prednisolone to the bioassay system failed to decrease somatomedin activity. We conclude that glucocorticoid administration is followed by an increase in circulating somatomedin inhibitors. Such inhibitors may explain the steroid-induced fall in net somatomedin activity and contribute to impaired growth. PMID- 4031008 TI - Human chorionic gonadotropin and 8-bromo-adenosine 3',5'-monophosphate stimulate [125I]low density lipoprotein uptake and metabolism by luteinized human granulosa cells in culture. AB - In nonsteroidogenic cells, cellular cholesterol requirements and sterol availability determine low density lipoprotein (LDL) receptor expression and LDL metabolism. We wished to learn if hCG and cAMP increase LDL metabolism by cultured luteinized human granulosa cells and whether this increase is dependent on enhanced metabolism of cellular cholesterol stores to steroid. Granulosa cells were cultured for 48 h in medium containing 20% human male serum and then for 48 h in serum- and hormone-free medium. The cells then received either fresh medium (no additions) or one of the following treatments: 500 mIU hCG/ml, 1.5 mM 8-bromo cAMP, 100 micrograms aminoglutethimide (AG)/ml to inhibit cholesterol metabolism to steroid hormones, hCG plus AG, or 8-bromo-cAMP plus AG. After 6-48 h of exposure to tropic agents, specific metabolism of [125I]LDL was determined. hCG and 8-bromo-cAMP significantly increased (P less than 0.05) the amount of [125I]LDL bound (2.2-fold), internalized (2.3-fold), and degraded (2.9-fold) by the luteinized granulosa cells. The apparent Km values for LDL degradation in control and hCG-treated cells were similar (2.0 and 2.6 micrograms/ml, respectively). As little as 10 mIU hCG/ml stimulated LDL metabolism in a time dependent fashion: a stimulatory effect was detected within 6 h of exposure to hCG and was greater after 24 h. AG attenuated but did not prevent the hCG- or 8 bromo-cAMP-stimulated increase in both LDL uptake and metabolism, although it completely inhibited the steroidogenic response. AG alone had no significant effect on [125I] LDL metabolism. We conclude that hCG and cAMP increase LDL metabolism by luteinized human granulosa cells. These effects are apparently not simply a consequence of enhanced cellular cholesterol metabolism to steroids. PMID- 4031009 TI - Absence of intercavernous venous mixing: evidence supporting lateralization of pituitary microadenomas by venous sampling. AB - Preoperative lateralization of endocrine-active pituitary tumors may be possible by bilateral inferior petrosal sinus (IPS) sampling for hormone measurement. The reliability of this technique depends on unilateral drainage of blood from the adenoma within the pituitary gland, in its course from the gland to the ipsilateral cavernous sinus, and from the cavernous sinus to the junction of the IPS and the internal jugular vein. Anatomical studies demonstrate unilateral drainage of each hemihypophysis into the ipsilateral cavernous sinus. The degree of mixing of blood between the cavernous sinuses, via the intercavernous sinus, and between the IPSs, via the basilar plexus, is unknown. We determined the extent of mixing of blood flowing from the superior orbital vein to the junction of the IPS and the internal jugular vein in four rhesus monkeys. After catheterization of a superior orbital vein and both IPSs, 99Tc-colloidal sulfur was infused into the superior orbital vein while blood samples were taken simultaneously from both IPSs and a peripheral vein at 3-min intervals. Mean relative radioactivity was 100 +/- 14% (+/- SEM) in the ipsilateral IPS, 8 +/- 2% in the contralateral IPS, and 3 +/- 1% in a peripheral vein. Isotope reaching the ipsilateral IPS before recirculation from the periphery was 10- to 313-fold more concentrated than in the contralateral IPS. These findings suggest that mixture of blood between the cavernous sinuses and between the IPSs is insignificant and support the capability of preoperative lateralization of pituitary microadenomas by bilateral and simultaneous IPS sampling. PMID- 4031011 TI - Opioid peptides in human adrenal: partial characterization and presence of adrenal peptide E. AB - Evaluation of hypotheses concerning the role of opioid peptides in the human adrenal is handicapped by the lack of information concerning the nature of these peptides. We studied the content of opioid peptides in whole adrenal tissue using several RIAs, including one which cross-reacts with all opioid peptides tested. Opioid peptides were localized to granules which behaved like chromaffin granules on crude sucrose density separation. beta-Endorphin immunoreactivity was a minor component, which was found principally in the form of beta-endorphin-(1-31). The majority of the remaining peptides probably were products of proenkephalin. The human postmortem tissue differed from bovine tissue in that the major accumulating products of this precursor were the size of the enkephalins and their small congeners, and not the intermediate-sized (mol wt, approximately 1500 4000) peptides that predominated in bovine tissue. We also found evidence of the presence of the 25-amino acid complex opioid, peptide E, in human tissue. PMID- 4031010 TI - Influence of age on steroid concentrations in skin and striated muscle in women and in cardiac muscle and lung tissue in men. AB - In order to investigate whether androgen concentrations vary as a function of age in all tissues and organs and whether the sexual differences in plasma androgen levels are reflected in tissue concentrations, testosterone (T), 5 alpha androstane-17 beta-ol, 3-one (DHT), 5 alpha-androstane-3 alpha,17 beta-diol (Adiol), and 4-androstene-3,17-dione (Adion) concentrations were measured postmortem in lung tissue and myocardium of men aged 16-87 yr. The results were compared to values obtained previously in other tissues. Similar measurements were made in various tissues (labia majora, clitoris, pubic skin, thigh skin, striated muscle) from women aged 16-87 yr. In cardiac tissue of men, T was quantitatively the most important androgen and concentrations of DHT and Adiol were low, reflecting low 5 alpha-reductase activity; in lung tissue, T and Adion were found in similar concentrations, with lower levels of 5 alpha-reduced metabolites. In both cardiac and lung tissue, androgen concentrations decreased significantly with age. In women, androgen concentrations were highest in specific androgen target tissues (labia majora, clitoris) and lowest in thigh skin and striated muscle. The ratios of the 5 alpha-saturated metabolites (DHT plus Adiol) to T or to T + Adion, respectively, parallel total androgen concentrations, whereas the Adiol to DHT ratio, a parameter of 3 alpha-reductase activity, was highest in striated muscle and thigh skin and lowest in androgen target tissues (labia majora and clitoris). In women tissue concentrations of all androgens decreased significantly with age in nearly all tissues studied. As expected tissue androgen concentrations were lower in women than in men, but in androgen target tissues such as the clitoris or labia majora, concentrations were little lower than in scrotal skin. We conclude that in both men and women androgen target tissues contain high androgen concentrations and high 5 alpha reductase activity; moreover androgen concentrations in target tissues are similar in both sexes. In both sexes tissue androgen concentrations decreased with age in most tissues, but in target tissues the decrease was more pronounced in women than in men. PMID- 4031012 TI - Serum ferritin as a marker of thyroid hormone action on peripheral tissues. AB - Serum ferritin measurements were evaluated as a marker of thyroid hormone action on peripheral tissues. Mean serum ferritin concentrations were not significantly different in euthyroid, thyrotoxic, and hypothyroid subjects due to a wide spread in ferritin levels among individuals. Intraindividual changes in serum ferritin, however, occurred with changing thyroid function. All 18 patients with thyrotoxic Graves' disease had a decrease in serum ferritin levels when they became euthyroid during antithyroid drug therapy. Furthermore, a significant intraindividual correlation between serum levels of ferritin and T4 or T3 was found in 2 patients with thyrotoxic Graves' disease in whom levels were measured serially throughout the course of therapy. Similarly, serum ferritin levels increased in all 12 hypothyroid patients with Hashimoto's disease when euthyroidism was achieved with L-T4 therapy. Administration of 75 micrograms T3 daily for 1 week to 11 euthyroid subjects resulted in a 23-243% (mean +/- SD, 117 +/- 70%) increase in serum ferritin above basal values. In contrast, in 3 patients with thyroid hormone resistance, the same treatment produced rises in serum ferritin concentrations of only 2%, 5%, and 15%. Our data suggest that alterations in thyroid status in a given individual produce changes in serum ferritin levels. Measurement of this protein before and after T3 therapy may prove useful in the diagnosis of thyroid hormone resistance. PMID- 4031013 TI - Bromocriptine effects on cultured human prolactin-producing pituitary adenomas: in vitro ultrastructural, morphometric, and immunoelectron microscopic studies. AB - In an effort to better characterize the ultrastructural, morphometric, and immunocytochemical changes induced by 10(-8) M bromocriptine (BR), tumor cells from three surgically removed PRL-producing pituitary adenomas were cultured on an extracellular matrix in serum-free medium. In each instance, the treated cultures were compared to control cells at the end of 24 h and 16 days. PRL RIAs were performed on culture medium. A decrease in cell and nucleus surface area was found on day 16 in two cultures. This supports the well known shrinkage of BR treated PRL-producing adenomas. BR induced no change in these parameters in the tumor from a third patient who was partly resistant to the drug. Changes in the secretory process were discernible as of day 1 in all three tumors, with a dramatic reduction of exocytosis and intracellular accumulation of PRL immunoreactive granules. This induced delayed inhibition of protein synthesis, demonstrated by preembedding immunocytochemistry on day 16. These results, obtained for the first time in human PRL-producing adenomas, are informative as to the subcellular events subsequent to short term BR treatment and illustrate that secretory inhibition and tumor shrinkage are not necessarily linked. PMID- 4031014 TI - Black (or brown) adrenal cortical adenoma: its characteristic features on computed tomography and endocrine data. AB - Seventeen patients with adrenal adenoma causing Cushing's syndrome, eight patients with Cushing's disease due to hypersecretion of ACTH, and five patients with primary aldosteronism due to an aldosteronoma were studied for their computed tomographic (CT) patterns, hormonal profiles, and macroscopic and microscopic findings of the adrenal gland. Black (or brown) adrenal adenomas were found in 71% of the patients with Cushing's syndrome, but not in patients with aldosteronoma. The adrenal tissue of patients with Cushing's disease was predominantly yellow. The number of compact cells was larger in black or brown adenomas than in yellow tumors or hyperplastic adrenal tissue. In patients with Cushing's syndrome, urinary excretion of 17-ketosteroids (17-KS) and serum aldosterone concentrations were lower in those with black or brown adenomas than in those with yellow adenomas (P less than 0.05). Patients with Cushing's disease had even higher 17-KS and serum aldosterone levels. No difference was found in serum cortisol concentrations and dexamethasone suppressibility in two types of adenomas causing Cushing's syndrome. Visual estimation of radiological density of the adrenal tissue relative to the kidney on CT scan and quantitative measurement of it by CT number revealed a difference between the two types of adrenal tumors causing Cushing's syndrome. Adrenal tumors with decreased density on CT scan were yellow adenomas with predominantly clear cells, and those with equal or increased density were black or brown adenomas with predominantly compact cells. All aldosteronomas had decreased density and consisted of clear cells. It is suggested that black or brown adenomas of the adrenal gland have higher radiological density and accompanying lower serum aldosterone and urinary 17-KS levels than ordinary yellow tumors. The abundance of compact cells may have some significance for the development of this particular type of adrenal tumor. PMID- 4031015 TI - Prolonged treatment of Cushing's disease by ketoconazole. AB - Ketoconazole, used in clinical practice as an antifungal medication, recently was found to be a potent inhibitor of gonadal and adrenal steroidogenesis in vitro and in vivo. The effects of prolonged treatment with this agent in Cushing's disease were investigated in five patients who had recurrent severe hypercortisolism after selective transsphenoidal surgery. The patients received the drug for at least 2 months. Urinary cortisol markedly decreased in all patients immediately after the beginning of treatment with ketoconazole (800 mg/day) and remained within low normal levels when the daily dose was lowered to 600 mg/day. Plasma cortisol also decreased. After 4-6 weeks of treatment, the clinical features of the disease regressed in all patients without signs of toxicity. These findings indicate that ketoconazole may be a valuable drug for the management of patients with Cushing's disease because of its ability to correct hypercortisolism quickly. PMID- 4031016 TI - Fatty acid compositions of serum lipids, erythrocytes, and platelets in insulin dependent diabetic women. AB - The fatty acid composition of serum lipids, erythrocytes, platelets, and diet was studied in women with insulin-dependent diabetes (IDDM) and in normal subjects matched for age, sex, body weight, and serum lipid levels. The dietary intake of linoleic acid was higher in IDDM patients than in the normal subjects. The linoleic acid content of serum triglycerides, cholesterol esters, and phospholipids and of red cells and platelets were elevated in patients with IDDM proportionately to their dietary linoleate intake. The linoleic acid content of serum lipids, but not of diet, was significantly correlated with glycosylated hemoglobin A1c in IDDM patients. However, the serum lipid content of arachidonic acid and other n-6 polyunsaturated fatty acids, which are metabolites of linoleic acid, was decreased in IDDM patients, but these metabolites were normal or increased in their cell membranes. The contents of n-3 polyunsaturated fatty acids were decreased in serum and platelet lipids and tended to be increased in erythrocyte membranes of diabetic patients. The results suggest that elongation and desaturation of essential fatty acids, linoleic acid in particular, are decreased in women with IDDM. PMID- 4031017 TI - Comparison of iodobenzylguanidine imaging with computed tomography in locating pheochromocytoma. AB - Ninety-nine patients suspected of having pheochromocytoma were studied with [131I]metaiodobenzylguanidine scintigraphy, and 92 of them were studied with computed tomography (CT). In 49 patients, the diagnosis was ruled out; in 3 patients, it remained doubtful; and in 47 patients, it was confirmed. Two patients had tumors that did not secrete epinephrine or norepinephrine, and 45 had secreting pheochromocytomas. In these latter patients, there were 4 false negative [131I]metaiodobenzylguanidine scans, all intraadrenal tumors, and 4 false negative CT scans, 3 extraadrenal and 1 intraadrenal tumors. For about 80% of the patients and/or the tumor sites, both methods were thus in agreement. They were complementary in the remaining 20%. The advantage of scintigraphy is to screen the whole body with high specificity and to locate extra-adrenal sites or metastases of pheochromocytoma with better accuracy than CT. The limits of scintigraphy are the possibility of false negative scans in around 10% of patients, whereas CT visualizes more than 95% of intraadrenal tumors. PMID- 4031018 TI - Hepatic bioavailability of thyroxine and testosterone in familial dysalbuminemic hyperthyroxinemia. AB - The bioavailability of [125I]T4 or [3H]testosterone in serum obtained from normal subjects and from subjects with familial dysalbuminemic hyperthyroxinemia (FDH) was studied with a portal vein injection technique in ketamine-anesthetized rats. In the present studies this technique was modified by performing uptake measurements in the presence of serum loaded with either 25 microM T4 or 1 microM testosterone. Loading of serum with these high concentrations displaced the labeled hormone from the lower capacity globulin or prealbumin-binding sites to the high capacity albumin or dysalbumin-binding sites, and allowed for the analysis of hormone availability in liver when the labeled hormone was delivered to the tissue bound either to albumin or to dysalbumin binding sites. In the presence of normal serum, 33 +/- 3% (SE) of T4 was available to rat liver, as opposed to 20 +/- 2% for FDH serum. When normal serum was loaded with 25 microM T4, the bioavailable T4 increased to 97 +/- 2%, consistent with the availability of T4 bound to albumin. However, the hepatic bioavailability of T4 in the presence of 25 microM T4 in FDH serum was only 33 +/- 4%. Testosterone bioavailability was similar in normal and in FDH sera, and was 49 +/- 7% in the absence and 99 +/- 4% in the presence of 1 microM testosterone. These studies suggest that T4 bound to the FDH albumin binding site is not readily available for entry into liver, whereas T4 bound to the normal albumin binding site is freely available for uptake in vivo. The differential bioavailability of T4 is compatible with the model that the normal and FDH binding sites are situated on different parts of the albumin molecule, and that only T4 bound to the normal binding site is freely available for delivery to the liver. PMID- 4031020 TI - WAIS and neuropsychological tests: common and unique variance within an epileptic population. AB - Neuropsychological assessment batteries, which traditionally require lengthy administration times, may be composed of multiple tests which measure essentially the same performance attributes. Test redundancies of this nature compromise the adequacy of a test battery from a cost containment perspective. The present study evaluated the common and unique variance of the WAIS relative to a modified and expanded Halstead-Reitan test battery to determine if information obtained from the WAIS is sufficiently nonredundant to justify its inclusion as part of this assessment battery. Cross-validated estimates of bivariate and multivariate relationships between these instruments were generated from two samples (n = 125) of epileptics. Results indicated statistically significant redundancies, yet, when interpreted from a clinical perspective it was evident that neuropsychological tests could not accurately duplicate information provided by the WAIS. Accordingly, it was not recommended that the WAIS be eliminated from this test battery in order to reduce test administration time. PMID- 4031019 TI - Endogenous opiates participate in the regulation of pulsatile luteinizing hormone release in an unopposed estrogen milieu: studies in estrogen-replaced, gonadectomized patients with testicular feminization. AB - Administration of opiate receptor antagonists augmented pulsatile LH release in six estrogen-treated, orchidectomized individuals with testicular feminization. In response to an opiate antagonist, LH pulse frequency increased from 3.0 +/- 0.55 (+/- SE) to 5.0 +/- 0.45 pulses/8 h (P = 0.034). Since these patients have inborn target tissue resistance to androgens, we infer that sustained androgen action is not obligatory to the emergence of endogenous inhibitory opiate tone in man. Rather, these observations document that the suppressive effects of opiates on gonadotropin secretion can be unmasked in the presence of an unopposed estrogen milieu. PMID- 4031021 TI - Utility of the Seashore Tonal Memory Test in neuropsychological assessment. AB - This study assessed the diagnostic utility of the Seashore Tonal Memory Test in detecting and localizing cerebral lesions. A group of 238 subjects with focal or diffuse cerebral lesions and a group of 112 normal comparison subjects were administered the Seashore Tonal Memory Test and the Halstead-Reitan Battery. All brain-damaged subgroups did significantly worse than the normal group on the Tonal Memory Test. Patients with right-hemisphere lesions were more impaired on this test than were those with left-hemisphere lesions. In contrast, Seashore Rhythm Test scores were not significantly different for groups with right- versus left-hemisphere lesions. Tonal Memory performance was not found to be related to more precise location of structural lesions within the right hemisphere. Step wise discriminate function analyses indicated that the Tonal Memory Test adds to the Halstead-Reitan Battery in discriminating left-hemisphere from right hemisphere lesions and that, for this purpose, it was a better discriminator than all but one of the individual tests currently in the battery. PMID- 4031022 TI - Can spatial deficits in Turner's syndrome be explained by focal CNS dysfunction or atypical speech lateralization? AB - The spatial impairments of Turner's Syndrome were examined by administering perceptual, constructional, and nonverbal memory tasks to 11 probands and 22 controls matched for phenotypic sex, age, education, and hand preference. Visual imperception was more pronounced than constructional apraxia. Deficits in attention span were present, but they were not restricted to the visual modality or to nonverbal stimuli. Further neuropsychological tests of focal brain dysfunction and speech lateralization revealed slightly increased somatosensory thresholds of the left palm, attenuated manual asymmetry, and diminished right visual-field superiority on letter identification. Different measures of spatial ability correlated with the somatosensory scores, the manual scores, and the speech representation scores, but the latter three variables showed no significant interrelationships. It is concluded that a unitary explanation in terms of focal CNS dysfunction or atypical speech representation can not account for the pattern of neuropsychological deficits seen in Turner's Syndrome. PMID- 4031023 TI - Some amnesic patients can freely recall large amounts of information in new contexts. AB - A previously reported technique for promoting robust free recall in amnesic subjects (Ridiculously Imaged Stories) was further studied in two amnesic patients to determine if there is a limit to the amount of information that can be acquired, and if the novelty of the storyline is essential for its efficacy. Two different lists of words were taught to each subject embedded in either a ridiculous or a logical story. The subjects learned combined totals of 160 (S1) and 120 (S2) words with perfect free recall at intervals up to 7 weeks between last list exposure and recall. No differences were observed in rates of learning between the two types of stories. These results challenge the view that amnesic subjects are unable to freely recall large amounts of new information within a newly acquired context. A theoretical integration of the data is explored. PMID- 4031024 TI - Use of demographic variables to predict full scale IQ: a replication and extension. AB - The evaluation of current level of neuropsychological functioning is handicapped by the lack of validated actuarial methods for estimating premorbid intellectual functioning. The present study cross-validated and attempted to improve the one existing method of using demographic variables in a systematic way to predict WAIS Full Scale IQ (Wilson et al., 1978). A sample of 491 neurologically normal subjects was used. The results generally supported the IQ prediction equation, but did reveal systematic differences in accuracy of prediction and direction of prediction error for IQs in the high and low ranges. Also, a simpler IQ prediction formula that uses only years of education was developed and compared with the 5-variable Wilson et al. formula. PMID- 4031025 TI - Effects of localized lesions on the Verbal Concept Attainment Test. AB - This study examined the performance of groups of patients (n = 97) with independently localized cerebral lesions on the Verbal Concept Attainment Test (VCAT). It was found that the left frontal group was impaired relative to all the other-lesion groups. In addition frequency distributions were examined in the lesion groups and a large normative sample (n = 360). Although the means of the other-lesion groups were below that of controls, the left frontal group had the lowest mean score, and was characterized by an absence of relatively good scores. Possible cut-off scores were examined for potential clinical utility. The data were discussed in relation to previous studies of frontal-lobe behavioral deficits and in relation to the potential clinical utility of the VCAT in detection of frontal-lobe dysfunction. PMID- 4031026 TI - Contribution of the TPT to adult neuropsychological assessment: a review. AB - The Tactual Performance Test (TPT) is reviewed because of its widespread use in neuropsychology. The review indicates that: (1) each of the three TPT scores (Time, Memory, Location), while having considerable overlap in what is measured, contributes something unique; (2) test-retest reliability is adequate, although TPT Memory and Location are generally less reliable than TPT Time; (3) TPT Time has proven to be a sensitive and valid measure of dysfunction in heterogeneous populations of brain-damaged subjects; (4) subject variables of importance to TPT performance are age, IQ, sex, and, to a much less extent, education; (5) there are indications that TPT Time is somewhat more sensitive to right-hemisphere dysfunction, at least in acutely brain-damaged subjects; (6) in more chronic cases, the TPT may be more sensitive to extent of damage than locus of lesion; (7) in obtaining lateralizing information, TPT Time scores for each hand are most helpful; and, (8) additional information may be obtained through examining individual trial scores, pattern across three trials, and observing the subject's strategy in completing the task. Modifications and implications for rehabilitation are discussed. PMID- 4031027 TI - Analysis of covariance as a remedy for demographic mismatch of research subject groups: some sobering simulations. AB - Analysis of Covariance (ANCOVA) is often used in neuropsychological studies to effect ex-post-facto adjustment of performance variables amongst groups of subjects mismatched on some relevant demographic variable. This paper reviews some of the statistical assumptions underlying this usage. In an attempt to illustrate the complexities of this statistical technique, three sham studies using actual patient data are presented. These staged simulations have varying relationships between group test performance differences and levels of covariate discrepancy. The results were robust and consistent in their nature, and were held to support the wisdom of previous cautions by statisticians concerning the employment of ANCOVA to justify comparisons between incomparable groups. ANCOVA should not be used in neuropsychological research to equate groups unequal on variables such as age and education or to exert statistical control whose objective is to eliminate consideration of the covariate as an explanation for results. Finally, the report advocates by example the use of simulation to further our understanding of neuropsychological variables. PMID- 4031028 TI - Improved utility of Gonoscreen, a Limulus amoebocyte lysate assay, in the evaluation of urethral discharges in men. AB - The Limulus amoebocyte lysate (LAL) assay was improved for the rapid evaluation of exudative urethritis in males. Two hundred men with various quantities of urethral discharge were evaluated. Pyrogen-free Dacron swabs were used for sample collection, and a chromogenic substrate was used for visible endpoint determination after a 10-min incubation. Of the 200 patients studied, 57 (29%) had minimal urethral discharges (less than 15 microliter) and could not be evaluated with Gonoscreen (Mallinckrodt, Inc., St. Louis, Mo.), an LAL test kit for the evaluation of urethritis which involves gentle aspiration for sample collection. The improved LAL assay had a sensitivity and specificity of 95 and 97%, respectively, and an overall accuracy to predict culture results of 96%. These results were not statistically different from Gram-stained smears read by experienced microscopists or from culture results (P greater than 0.05). Prevalence of gonorrhea in the study population was 40%, and the positive predictive value of the LAL assay was 95%. Thus, the use of swabs facilitated sample collection and increased by 29% the number of patients which could be evaluated with the LAL assay. In addition, the use of a chromogenic substrate reduced incubation time by 67% (30 to 10 min) and provided an objective color endpoint. PMID- 4031029 TI - Occurrence of Streptococcus milleri among beta-hemolytic streptococci isolated from clinical specimens. AB - A total of 256 beta-hemolytic streptococcal isolates were subjected to serological and physiological tests to identify those which could be classified as Streptococcus milleri. S. milleri accounted for 75% of 70 group C isolates, 15% of 69 group G isolates, 75% of 16 nongroupable isolates, and 100% of 20 group F isolates examined. No S. milleri isolates were encountered among the 90 group A streptococci studied. Of the 95 beta-hemolytic S. milleri isolates examined, 81% were recovered from respiratory specimens. PMID- 4031030 TI - Simplified bioassay method for measurement of flucytosine or ketoconazole. AB - A simple agar-well diffusion bioassay suitable for measurement of flucytosine or ketoconazole was developed by using Candida pseudotropicalis ATCC 46764 as the assay organism. A test medium composed of (per liter) 7 g of Trypticase peptone, 7 g of YNB (yeast-nitrogen base), 15 g of glucose, and 15 g of agar was seeded with an inoculum which had been grown to no. 2 McFarland turbidity after 4 to 6 h in YNB-glucose broth. Determinations of flucytosine or ketoconazole were performed without necessity of heating or diluting of serum samples to alleviate amphotericin B interference. A linear relationship between zone diameters and log10 concentration of the drugs was observed over the pharmacologically relevant ranges of 25 to 160 micrograms/ml for flucytosine and 0.5 to 20 micrograms/ml for ketoconazole. The mean coefficient of variability for samples measured on 5 separate days was 2.4% for flucytosin and 4.0% for ketoconazole. This assay represents a significant improvement over previous bioassay methods in that a single test system may be used for measurement of either flucytosine or ketoconazole, no serum dilution or pretreatment is required, inoculum preparation is accomplished entirely on the day of the assay, and sharp, clearly defined zones of inhibition are obtained with both drugs. PMID- 4031031 TI - New serotypes of Treponema hyodysenteriae. AB - Three isolates of pathogenic Treponema hyodysenteriae, B8044, B6933, and Ack 300/8, were serotyped by double immunodiffusion using lipopolysaccharide antigen and rabbit antiserum. The precipitation reactions of these three isolates were then compared with precipitin reactions from the reference strains of serotypes 1 through 4. The data indicated that B8044, B6933, and Ack 300/8 share antigenic determinants with either serotype 1 or 2 or both. However, when the cross reacting antibodies were removed by adsorption, all reactions were found to be monospecific. Based on these results, three new serotypes of pathogenic T. hyodysenteriae are proposed: B8044 serotype 5, B6933 serotype 6, and Ack 300/8 serotype 7. PMID- 4031032 TI - Fungal peritonitis caused by Lecythophora mutabilis. AB - Fungal peritonitis caused by Lecythophora mutabilis, a mold rarely isolated from humans, is described. A patient on continuous peritoneal dialysis developed clinical, microbiological, and serological evidence for peritonitis due to this fungus. In vitro susceptibility testing of the fungus revealed marked differences in the activities of various antifungal agents. Although initially responding to treatment with oral ketoconazole, intraperitoneal miconazole, and catheter replacement, the patient had a documented relapse. The patient was eventually cured following the removal of a second catheter in association with prolonged imidazole treatment. PMID- 4031033 TI - Automated reading of MIC microdilution trays containing fluorogenic enzyme substrates with the Sensititre Autoreader. AB - The Sensititre Autoreader is a microcomputer-driven instrument capable of automatically reading antimicrobial susceptibility microdilution trays. The instrument measures the fluorescence liberated by bacterial enzymatic activity on fluorogenic substrates as an indicator of growth in each well. A mathematical algorithm converts the fluorescent signals from an antimicrobial dilution series to an MIC endpoint. A three-center study evaluated the performance of the Autoreader in comparison with MIC determined visually in a duplicate set of control plates lacking fluorogenic substrate. Among 828 isolates of gram-negative bacilli tested against 17 antimicrobial agents, Autoreader 18-h MIC were within +/- 1 twofold dilution of control MIC values (agreement) in 95.3% of instances. In 3.5% of the instances, Autoreader values occurred +/- 2 half-step dilutions from control values (minor discrepancy), and in only 1.2% of instances did Autoreader values deviate from control values by greater than +/- 2 dilution steps (major discrepancy). Agreement, minor discrepancies, and major discrepancies were noted among 148 gram-positive cocci tested against 11 antimicrobial agents in 93.5, 4.8, and 1.7% of the instances, respectively. Over half of the major discrepancies noted with gram-negative bacilli occurred with Proteus mirabilis-beta-lactam combinations, a problem that was resolved when a lower initial inoculum was used. Inter-and intralaboratory reproducibility was excellent. Standard Sensititre susceptibility trays may be instrument read at 18 h reproducibly and accurately with only slight modification of conventional procedures to include fluorogenic enzyme substrates in the incubation broth. PMID- 4031035 TI - Comparison of the FeKal CON-Trate system with the formalin-ethyl acetate technique for detection of intestinal parasites. AB - The ability of the FeKal CON-Trate system (Trend Scientific, Minneapolis, Minn.) to recover parasite ova, cysts, or larvae from 300 fecal specimens was compared with that of the Formalin-ethyl acetate sedimentation technique. One hundred stool samples had previously been determined to contain 129 parasite forms. The FeKal system detected 127 parasites (sensitivity, 98.4%), and the Formalin-ethyl acetate sedimentation technique detected 125 parasites (sensitivity, 96.9%). Higher counts of parasite forms were obtained for 11 of 14 species of parasites in specimens prepared by the FeKal system. Four specimens were negative by the Formalin-ethyl acetate method and two by the FeKal system. These false-negative observations occurred in specimens with low counts of parasites. There were no false-positive results. PMID- 4031034 TI - Serum susceptibility of Haemophilus somnus from bovine clinical cases and carriers. AB - The serum susceptibility of 64 isolates of Haemophilus somnus from cattle was determined in a bactericidal assay with undiluted fresh or inactivated bovine serum with serial dilutions of bacterial suspension in RPMI 1640 medium. A total of 27 strains isolated from cattle with clinical disease (4 with thromboembolic meningoencephalitis, 13 with pneumonia, and 10 with reproductive failure) were compared with 35 strains from asymptomatic carriers (11 from the vagina and 24 from the prepuce). Essentially, all clinical isolates were serum resistant, whereas approximately 25% of preputial isolates were serum susceptible, as judged after 1 h of incubation in serum; a majority of vaginal isolates showed delayed serum susceptibility. Lysozyme played no role in serum killing, and the alternative complement pathway played only a minor role. Iron saturation, however, appeared to impart greater serum resistance to serum-susceptible strains from the vagina and prepuce. Perhaps the serum-susceptible strains from carriers would be useful vaccine candidates, but resistant strains from carriers may be pathogenic. PMID- 4031036 TI - Antimicrobial susceptibility testing of Francisella tularensis with a modified Mueller-Hinton broth. AB - A modified Mueller-Hinton broth was developed to perform antimicrobial susceptibility tests on Francisella tularensis. Adequate growth of the organism was obtained within 24 h of inoculation, and MICs could be read at that time. We tested 15 selected strains of F. tularensis and five reference quality control strains in this medium with 36 antimicrobial agents. The MICs of the aminoglycosides and tetracycline increased 1 to 3 dilutions in this medium compared with those in the usual medium, but the other antimicrobial agents were not consistently affected by the medium. Even though the medium caused an increase in MICs, the aminoglycosides and tetracyclines remained very active in vitro against F. tularensis. Other antimicrobial agents effective in vitro were chloramphenicol, erythromycin, ceftazidime, moxalactam, cefotaxime, ceftriaxone, and Sch 29482 (a cephalosporin). PMID- 4031037 TI - Aggregation of platelets by Fusobacterium necrophorum. AB - Broth cultures and washed cells of 13 of 24 bovine isolates of Fusobacterium necrophorum aggregated human platelets in platelet-rich plasma. The cell-free culture fluid was inactive. Bacteria stored at 4 degrees C in saline remained active for at least 3 months, but they did not release activity into the storage solution. Aggregation typically began within 1 min after the addition of 10(3) bacteria to 10(3) platelets was complete within 5.5 min. Assays for cytosolic lactic dehydrogenase revealed that platelet lysis did not occur. The release of [14C]serotonin from platelets preincubated with this amine accompanied aggregation, indicating that this was a typical aggregation-degranulation reaction. Platelet aggregation was inhibited by EDTA (88% at 2.0 mM), aspirin (75% inhibition at 1.0 mM), and quinacrine (80% inhibition at 0.25 mM). Thus the reaction was an ion-dependent, cyclooxygenase-sensitive event. Gel-filtered platelets were less sensitive to aggregation than were platelets in plasma, but this sensitivity was fully restored by the addition of plasma and partially restored with fibrinogen. Biotyping of the cultures revealed that none of the avirulent, B-type strains of F. necrophorum could aggregate platelets, whereas 13 of 16 virulent A type strains were positive. These results suggest that platelet aggregation by F. necrophorum is related to the virulence of this organism. PMID- 4031038 TI - Simplified plaque reduction neutralization assay for dengue viruses by semimicro methods in BHK-21 cells: comparison of the BHK suspension test with standard plaque reduction neutralization. AB - A newly modified semimicro plaque reduction neutralization test (PRNT) in BHK cells was compared with a standard PRNT in bottles with LLC-MK2 monolayers and with an LLC-MK2 PRNT adapted to semimicro methods. The BHK semimicro PRNT compared favorably in terms of sensitivity in detecting dengue antibody (96%), specificity at a screening dilution (95%), and ability to detect seroconversion to dengue viruses of three serotypes (93%). Disagreements between the BHK test and the LLC-MK2 tests were attributed to greater sensitivity of the BHK test in detecting dengue type 2 (DEN-2) antibody in acute-phase sera and to apparent low level DEN-1/DEN-3 cross-reactions in some sera in all three tests. The BHK PRNT was easier, faster, and more economical than either of the LLC-MK2 tests. Many of the benefits of the BHK PRNT derive from the fact that cells are infected while still in suspension, at the time of cell splitting, hence the term "BHK suspension test." PMID- 4031040 TI - Experimental reproduction of Potomac horse fever in horses with a newly isolated Ehrlichia organism. AB - Potomac horse fever, a recently recognized disease of equines, characterized by high fever, leukopenia, and a profuse diarrhea, was studied for its etiology. An Ehrlichia organism was isolated in equine macrophage-fibroblast cell cultures and mouse macrophage cell cultures from the mononuclear cells of blood of infected horses. The agent was continuously propagated in mouse macrophage cell cultures. The organism multiplied in the cytoplasm of mouse macrophage cells and was identified by Giemsa staining, acridine orange staining, and by indirect immunofluorescence with convalescent sera from infected horses. The disease was experimentally reproduced in horses inoculated with Ehrlichia-infected cell culture material. The Ehrlichia organism was reisolated from the blood of these infected horses during the course of the disease. Antibody against the organism was detected in the sera of experimentally infected horses. This study confirmed that the new Ehrlichia organism is the etiological agent of Potomac horse fever. PMID- 4031039 TI - Subclass distribution and molecular form of immunoglobulin A hemagglutinin antibodies in sera and nasal secretions after experimental secondary infection with influenza A virus in humans. AB - Serum and nasal wash specimens from 13 human volunteers undergoing experimental secondary infection with influenza A/Peking/2/79 (H3N2) wild-type virus were examined for the molecular form and subclass distribution of immunoglobulin A (IgA) antibodies to the viral hemagglutinin (HA). Nasal IgA antibodies were polymeric and did not bind radiolabeled secretory component, indicating that they were secretory IgA antibodies. Both IgA1 and IgA2 antibodies were detected; however, IgA1 accounted for most of the rise in IgA anti-HA levels seen after infection. In serum virtually all of the IgA HA antibodies were of the IgA1 subclass. Furthermore, the serum antibodies were predominantly polymeric and were capable of binding radiolabeled secretory component. These results suggested that the serum IgA antibodies to HA were of mucosal origin and that influenza A virus HA preferentially stimulates an IgA1 response. PMID- 4031041 TI - Clinical appearance of orofacial infections of odontogenic origin in relation to microbiological findings. AB - Fifty-eight patients with acute orofacial infections of odontogenic origin were classified into two groups with respect to the severity of infection. A total of 174 anaerobic and 22 aerobic bacterial strains were isolated. Anaerobic gram negative rods were isolated more frequently from the patients with severe infections than from the patients with infections judged as mild (P less than 0.05). The occurrence of Fusobacterium nucleatum especially appeared to be associated with the severity of the infections (P less than 0.05). Penicillin resistance among the anaerobes was rarely found, while resistance to erythromycin was a common finding. All aerobic and anaerobic bacteria were susceptible to clindamycin, and all obligate anaerobic bacteria were susceptible to nitroimidazoles. PMID- 4031042 TI - Modified trichrome staining technique with a xylene substitute. AB - Hemo-De was evaluated and found to be a suitable replacement for xylene in the Wheatly trichrome staining of polyvinyl alcohol-fixed fecal smears used in the microscopic identification of intestinal protozoans. PMID- 4031043 TI - Spontaneous occurrence of Staphylococcus aureus mutants with different pigmentation and ability to produce toxic shock syndrome toxin 1. AB - Spontaneous mutants that have pigmentation different than that of their parents were isolated from three Staphylococcus aureus strains associated with toxic shock syndrome. These mutants produced toxic shock syndrome toxin 1 in amounts varying from less than 0.05 to greater than 25 times that produced by the parents. The occurrence of nonpigmented variants may be overlooked if only one isolate from a patient with toxic shock syndrome is selected for analysis. PMID- 4031044 TI - Isolation of Yersinia enterocolitica biotype 4 serotype O3 from canine sources in Italy. AB - Seventeen strains of Yersinia enterocolitica biotype 4 serotype O3 were isolated from 63 apparently healthy puppies. Of these strains, 76.4% showed both multiple resistance to antimicrobial agents and lack of sorbose fermentation. PMID- 4031046 TI - How common is meningitis caused by anaerobic bacteria? PMID- 4031045 TI - Leptotrichia buccalis bacteremia in neutropenic children. AB - Two new cases of Leptotrichia buccalis bacteremia in seriously ill patients were described. The anaerobic, gram-negative microorganism L. buccalis was isolated from blood cultures of two children with severe leukopenia. Anaerobic organisms should be taken into account when a standard protective antibiotic chemotherapy is considered in the immunosuppressed host. PMID- 4031047 TI - Biotyping schemes for Campylobacter jejuni. PMID- 4031048 TI - Dissociation between mechanical performance and the cost of isometric tension maintenance in Lethocerus flight muscle. AB - A method for the continuous measurement of ATP hydrolysis (ATPase) by demembranated muscle fibres has been applied to isometrically held, glycerol extracted flight muscle fibres from the water-bug Lethocerus, under conditions of high MgATP, neutral pH, and varying ionic strength, Ca2+ and extension. These variables caused parallel changes in isometric tension and ATPase. The slope of ATPase upon tension (delta ATPase/delta Tension; incremental tension cost) remained the same upon extension at either different Ca2+ concentrations or different ionic strength. Isometric activation by Ca2+ gave a higher incremental tension cost. The calculated mechanical rate constant of the work-producing process, measured by the small-amplitude behaviour, was increased by either Ca2+ or ionic strength, and little changed by extension; there was therefore a dissociation between its value and that of the incremental tension cost. The results appear to exclude a two-state crossbridge model for fibrillar insect flight muscle. PMID- 4031049 TI - Effect of quercetin on tension development by skinned fibres from frog skeletal muscle. AB - For proper interpretation of the results of drug-induced calcium release experiments with skinned fibres, it is necessary to know the direct effects of the drug on the contractile system. We examined the action of quercetin and its various solvents on mechanically skinned skeletal muscle fibre which is deprived of functioning sarcoplasmic reticulum by Triton X-100. Dimethyl sulphoxide (DMSO) at 1%, a solvent for quercetin, decreased reversibly Ca2+ sensitivity for the contractile system of frog skeletal muscle. Alcohol was similar to dimethyl sulphoxide. Polyethylene glycol was used as a solvent for quercetin, because the solvent at 1% was found to be inert to the pCa-tension relationship. Quercetin increased reversibly Ca2+ sensitivity of the contractile system with the unchanged maximum tension, the pCa-tension relationship being less steep. Since quercetin did not change calcium binding to troponin C from rabbit skeletal muscle, the effect may be due to modified molecular interactions which follow calcium binding to troponin C. The drug might also affect the interaction between troponin subunits. Because DMSO did not affect calcium binding to troponin C, either DMSO also modulates the interaction between troponin subunits and/or it modulates molecular interactions after calcium binding which lead to tension development. PMID- 4031050 TI - Hysteresis of the mammalian pCa/tension relation is small and muscle specific. AB - Small but statistically significant shifts (hysteresis) between the up (increasing tension direction) and down (decreasing tension) pCa/tension relation for several muscle types of the rabbit and rat were found. The largest shift is, at most, 0.093 p units or 60% of that reported for the barnacle muscle. The direction of shift for psoas is opposite to that for the soleus and tibialis. PMID- 4031052 TI - Health promotion in the workplace. PMID- 4031051 TI - Excitation-contraction coupling and contractile properties in denervated rat EDL and soleus muscles. AB - The long-term (up to ten weeks) effects of denervation on isometric tension and potassium (K) contractures were studied in isolated bundles of fibres from rat extensor digitorum longus (EDL) and soleus muscles, at 21 degrees C, bathed in solutions with low concentrations of chloride ions (to reduce the effects of high membrane chloride conductance). The usual increases in twitch time course and twitch for tetanus ratio were attributed to changes in excitation-contraction coupling because both developed between one to three weeks after denervation. Transient changes during the first week in the time course of the twitch and twitch to tetanus ratio in EDL, and post-tetanic twitch size and specific tension in both muscles, were attributed to the surface membrane electrical properties which are maximally altered within three days after denervation. In contrast to results obtained in solutions of normal chloride concentration, the resting membrane potentials of chronically denervated fibres were hyperpolarized and spontaneous action potentials and fibrillations were seen. The time to the peak of the K-contracture was faster than normal and very slow inactivation kinetics appeared in the decay phase. Mechanical repriming was normally slower in EDL than in soleus but similar rates were seen in the two muscles after denervation. These changes in the K-contracture were not due to a change in the relationship between membrane potential and potassium ion concentration. It is concluded that denervation caused changes in the kinetics of mechanical activation, inactivation and repriming and that these aspects of excitation-contraction coupling are normally controlled by an influence of the motor nerve. PMID- 4031053 TI - The neglect of injury prevention. PMID- 4031054 TI - Epidemiological research, interest groups, and the review process. PMID- 4031055 TI - Non-smoking policies in hospitals. PMID- 4031056 TI - A comparison of dental treatment plans under different reimbursement systems. PMID- 4031057 TI - Apolipoprotein B-100 deficiency. Intestinal steatosis despite apolipoprotein B-48 synthesis. AB - We describe a child, the issue of phenotypically normal parents, who had fat malabsorption, both intestinal and hepatic steatosis, and serum cholesterol and triglyceride concentrations of 38 and 63 mg/dl, respectively. Lipoprotein electrophoresis, Ouchterlony double diffusion, and electron microscopy demonstrated that normal low density lipoproteins (LDL: 1.006 less than rho less than 1.063 g/ml) were absent. Lipoprotein particles in the rho less than 1.006 g/ml fraction were triglyceride rich, very large (93.2 +/- 35.1 nm), and contained the B-48 but not the B-100 apoprotein; both species of apolipoprotein (apo) B were found in the parents' lipoproteins. These chylomicrons and chylomicron remnants were present even in the patient's fasting plasma, which suggested prolonged dietary fat absorption. Plasma levels of high density lipoprotein lipids and proteins were low, and the phosphatidylcholine/sphingomyelin ratio was reduced as in typical abetalipoproteinemia. The monosialylated form of apo C-III was not identified on polyacrylamide gel electrophoresis, which suggested that this protein was elaborated only with very low density lipoproteins (VLDL). A radioimmunoassay for apo B employing a polyclonal antisera to plasma LDL gave apparent plasma apo B levels of 0.6, 66, and 57 mg/dl in the patient and his father and mother, respectively. The displacement curve generated by the parents' VLDL and LDL did not did not differ from control lipoproteins. The patient's chylomicron chylomicron remnant fraction displaced normal LDL over the entire radioimmunoassay range, but the efficiency of displacement was strikingly less than with B-100 containing lipoproteins. If the patient's B-48 protein is not qualitatively abnormal, these results confirm very limited immunochemical cross reactivity between at least one major epitope on B-100 and the epitopes expressed on B-48. The apo B defect in this patient appears to be recessive. It abolishes B 100 production and may additionally limit the formation of B-48. PMID- 4031058 TI - Activation of factor XII-dependent pathways in human plasma by hematin and protoporphyrin. AB - Intravenous administration of hematin is effective in the treatment of acute exacerbations of the inducible porphyrias. In the course of such treatment, coagulopathies have occurred that are characterized by prolongation of prothrombin time, partial thromboplastin time, and formation of fibrin split products. In experiments in vitro with normal human plasma, we observed that hematin and protoporphyrin activated Factor XII-dependent pathways of coagulation and fibrinolysis, and that they generated kallikrein activity. Incubation of protoporphyrin with purified Factor XII resulted in activation as measured by amidolysis of a chromogenic substrate. Neither coproporphyrin, uroporphyrin, delta-aminolevulinic acid, porphobilinogen, or bilirubin activated Factor XII dependent pathways. Exposure of serum containing added uroporphyrin, coproporphyrin, and protoporphyrin, but not hematin, to ultraviolet light (405 nm) resulted in activation of the classical pathway of the complement system. On the other hand, exposure of plasma containing uroporphyrin or coproporphyrin to ultraviolet light did not result in activation of Factor XII-dependent pathways. PMID- 4031059 TI - Identification of gallbladder mucin-bilirubin complex in human cholesterol gallstone matrix. Effects of reducing agents on in vitro dissolution of matrix and intact gallstones. AB - The goals of this study were to isolate and characterize the nonlipid matrix of human cholesterol gallstones. The lipid portion of gallstones was dissolved in ethanol/ether, leaving an insoluble, granular, brown-black matrix that constituted 12.5% of solitary large stones and 3.5% of multiple small stones. The matrix was partially solubilized by sonication and studied by exclusion gel chromatography and density gradient ultracentrifugation. On Sepharose 2B column chromatography, bile pigment eluted with glycoprotein in the void volume, suggesting the presence of a high molecular weight complex (Mr greater than 2 X 10(6)). The identity of mucin in this complex was confirmed by its typical buoyant density during ultracentrifugation. The major bile pigments in the matrix were identified as bilirubin (84%) and bilirubin monoglucuronide (15%) by thin layer chromatography. Because of their ability to solubilize mucin-type glycoproteins, we tested the ability of the reducing agents 2-mercaptoethanol (2ME) and N-acetylcysteine (NAcCys) to solubilize gallstone matrix. Both reducing agents caused a two- to threefold enhancement of matrix dissolution after 4 d compared to aqueous buffer alone (P less than 0.01). Sepharose 2B chromatography revealed that 2ME released a high molecular weight mucin-bilirubin complex as well as unbound pigment from the insoluble matrix. We also tested the effect of reducing agents on dissolution of matched cholesterol gallstones by monooctanoin, a cholesterol solvent. Both 2ME and NAcCys significantly accelerated gallstone dissolution in monooctanoin. Matched human cholesterol stones (n = 10) incubated for 4 d in monooctanoin plus either 2ME or NAcCys (1 M final concentration) weighed approximately half as much (P less than 0.01 for each) as stones incubated in monooctanoin alone. This study describes, for the first time, the isolation of a bilirubin-mucin complex in the insoluble matrix of human cholesterol gallstones. The ability of reducing agents to dissolve the matrix and thereby accelerate gallstone dissolution by monooctanoin in vitro may be relevant to gallstone dissolution in humans. PMID- 4031060 TI - Systemic complement activation, lung injury, and products of lipid peroxidation. AB - Previously we have demonstrated that systemic activation of the complement system after intravenous injection of cobra venom factor (CVF) results in acute lung injury as reflected by increases in the vascular permeability of the lung as well as by morphologic evidence of damage to lung vascular endothelial cells. In using the vascular permeability of the lung as the reference, the current studies show a quantitative correlation between lung injury and the appearance in plasma of lipid peroxidation products (conjugated dienes) as well as increased concentrations of lactic dehydrogenase (LDH) and one of its isoenzymes (LDH-4). After injection of CVF, extracts of lungs also showed elevated levels of conjugated dienes, whereas no elevations were found in extracts of liver, kidney, and spleen. There was no evidence in CVF-injected rats of renal or hepatic injury as reflected by the lack of development of proteinuria and the failure to detect increased serum levels of liver-related enzymes. Other peroxidation products identified in plasma of CVF-injected rats involved hydroperoxides and fluorescent compounds with features of Schiff bases. Not surprisingly, malondialdehyde was not found to be a reliable plasma indicator of lipid peroxidation associated with oxygen radical-mediated lung vascular injury. In using a model of oxygen radical independent lung injury induced by oleic acid, although large amounts of LDH and LDH-4 were found in the plasma, no increases in plasma levels of conjugated dienes were detected. In CVF-injected animals treated with interventions protective against lung injury (neutrophil depletion, catalase, hydroxyl radical scavengers, or iron chelators), there were striking reductions in the plasma levels of conjugated dienes, hydroperoxides, and fluorochromic products. Morphometric analysis of lung sections revealed that the protective interventions did not interfere with the accumulation of neutrophils in lung interstitial capillaries after systemic activation of complement. In vitro studies with phorbol-stimulated neutrophils failed to demonstrate appearance of conjugated dienes, suggesting that the dienes appearing in plasma of CVF-injected animals are not the result of autotoxic changes in neutrophils. The data presented in this paper suggest that acute lung injury mediated by oxygen radicals derived from phagocytic cells can be monitored by the appearance in plasma of products of lipid peroxidation. PMID- 4031061 TI - Antiadhesive properties of biological surfaces are protective against stimulated granulocytes. AB - Despite the fact that a series of endogenous and exogenous inflammatory mediators are potent activators of circulating granulocytes, damage of vascular endothelium, a primary target tissue, is a rather unusual event in systemic inflammatory states. Since mediator-induced neutrophil hyperadhesiveness on plastic tissue culture dishes is invariably accompanied by intense release of lysosomal granule constituents and respiratory burst activation, thus representing a powerful model to investigate neutrophil cytotoxic states, comparative studies with neutrophils suspended in autologous plasma in the presence or absence of N-formyl-Met-Leu-Phe (2.5 microM), the most potent adhesion inducer, were performed on different biologic surfaces. On optimally adherent closed monolayers of cultured endothelial cells or fibroblasts we observed poor stimulation of adhesion as well as minimal granule release and hexose monophosphate pathway activation. Functional behavior of neutrophils on single molecular components of basal laminas such as fibronectin and collagen (type IV) coats was intermediate, with positive adhesion promotion but markedly reduced metabolic activation. When tested on endothelial cell-derived extracellular matrices, neutrophils again showed functional nonresponsiveness to N-formyl-Met-Leu-Phe. Scanning electron microscopy revealed an impressive congruency between the degree of cellular spreading and metabolic activation in the presence of N-formyl-Met-Leu-Phe, with maximally flattened neutrophils on plastic vs. nonspread, polarized cells on monolayers. Identical results were obtained by using other adhesion inducers such as complement-activated plasma or endotoxin. Lack of cell injury by N-formyl-Met-Leu-Phe-exposed neutrophils was corroborated by the absence of tracer release from [111In]tropolonate-labeled endothelium. These results indicate that biologic surfaces possess antiadhesive properties that protect them from cytotoxic damage by stimulated angry phagocytes. PMID- 4031062 TI - Paradoxical effects of pyrazinoate and nicotinate on urate transport in dog renal microvillus membranes. AB - The effects of pyrazinoate and nicotinate on urate transport in microvillus membrane vesicles isolated from canine renal cortex were evaluated. An outwardly directed gradient of pyrazinoate stimulated uphill urate accumulation, suggesting urate-pyrazinoate exchange. An inside-alkaline pH gradient stimulated uphill pyrazinoate accumulation, which suggested pyrazinoate-OH- exchange. Pyrazinoate OH- exchange and urate-OH- exchange were similarly sensitive to inhibitors, implying that both processes occur via the same transport system. In addition, an inward Na+ gradient stimulated uphill pyrazinoate accumulation, suggesting Na+ pyrazinoate cotransport. Inhibitor studies demonstrated that Na+-pyrazinoate cotransport takes place via the same pathway that mediates Na+-lactate cotransport in these membrane vesicles. Previously we found that urate does not share this Na+-dependent cotransport pathway. Nicotinate inhibited transport of pyrazinoate by the anion exchange pathway and the Na+ cotransport pathway, suggesting that it is a substrate for both transport systems. Finally, in the presence of an inward Na+ gradient, low doses of pyrazinoate or nicotinate stimulated urate uptake, and higher doses of pyrazinoate or nicotinate inhibited urate accumulation, thereby mimicking in vitro the paradoxical effects of drugs on renal urate excretion that have been observed in vivo. These findings indicate that the paradoxical effect of uricosuric drugs at low doses to cause urate retention may result at least in part from stimulation of urate reabsorption across the luminal membrane of the proximal tubular cell. PMID- 4031063 TI - Development of an integrated model for analysis of the kinetics of apolipoprotein B in plasma very low density lipoproteins, intermediate density lipoproteins, and low density lipoproteins. AB - To quantify more precisely the metabolism of apolipoprotein B (apo B) in human beings, an integrated model was developed for the analysis of the isotope kinetics of apo B in very low density lipoproteins (VLDL), intermediate density lipoproteins (IDL), and low density lipoproteins (LDL). The experimental basis for model development was a series of 30 triple-isotope studies in which patients received autologous 131I-VLDL, 125I-IDL, and [3H]glycerol as a precursor of VLDL triglycerides. The currently proposed model contains the following components: (a) a VLDL delipidation cascade that has a variable number of subcompartments, (b) a slowly catabolized pool of VLDL, (c) an IDL compartment consisting of two closely connected subcompartments, one of which is outside the immediate circulation, and (d) a two-compartment subsystem for LDL. Because mass data indicate that not all VLDL were converted to LDL, the model allows for irreversible removal of apo B from VLDL (or IDL) subsystems. It accounts for apparent "direct" input of LDL by postulating an early, rapidly metabolized compartment of VLDL that is converted directly to IDL. The model appears to be consistent with specific activity curves from the current triple-isotope studies and with present concepts of lipoprotein physiology; it also can be used to quantify pathways of lipoprotein apo B transport in normal and abnormal states. PMID- 4031064 TI - Influence of obesity on the metabolism of apolipoprotein B in humans. AB - The influence of obesity on the metabolism of apolipoprotein B (apo B) in very low density lipoprotein (VLDL), intermediate density lipoprotein (IDL), and low density lipoprotein (LDL) was investigated in nine obese and seven nonobese Pima Indian men. Kinetics of VLDL-apo B (VLDL-B), VLDL-triglycerides, IDL-B and LDL-B were studied after injection of autologous 131I-VLDL, [3H]glycerol, and autologous 125I-LDL. Specific activities were measured in apo B isolated from all lipoprotein fractions and in triglyceride isolated from VLDL. Transport rates and fractional catabolic rates for apo B in VLDL, IDL, and LDL and triglyceride in VLDL were determined by multicompartmental analysis. This method also allowed the estimation of rates of interconversions of the lipoproteins. The two groups had similar mean ages and heights, but the obese group had a higher total body weight (131 +/- 14 vs. 66 +/- 3 kg +/- SEM) and fat free mass (81 +/- 5 vs. 54 +/- 2 kg) than lean controls. Plasma total lipids were similar for the two groups, and apo B concentrations in VLDL, IDL, and LDL were similar in obese and lean subjects. In spite of similarity in concentrations, obese subjects compared to lean subjects had higher synthetic rates of VLDL-triglyceride (62.6 +/- 15 vs. 26.2 +/ 7 g/d, P less than 0.01), VLDL-B (2,241 +/- 215 vs. 1,113 +/- 72 mg/d, P less than 0.001), and LDL-B (1,234 +/- 87 vs. 802 +/- 83 mg/d, P less than 0.01). Furthermore, in obese subjects, significantly higher amounts of VLDL-B were removed from the circulation without conversion to LDL-B (1,078 +/- 159 vs. 460 +/- 34 mg/d, P less than 0.05), and obese subjects had a higher fractional catabolic rate for LDL than the lean controls (0.48 +/- 0.02 vs. 0.41 +/- 0.02 d 1, P less than 0.05). The rapid catabolism of LDL and increased metabolism of VLDL without conversion to LDL in obese individuals may be mechanisms for maintenance of LDL at normal levels despite the overproduction of its precursor. PMID- 4031065 TI - Diminished type I collagen synthesis and reduced alpha 1(I) collagen messenger RNA in cultured fibroblasts from patients with dominantly inherited (type I) osteogenesis imperfecta. AB - Type I osteogenesis imperfecta (OI) is characterized clinically by a moderate fracture frequency with minimal bone deformity and dominant inheritance. Previous studies of the collagenous proteins synthesized by dermal fibroblasts obtained from unrelated patients with this form of OI suggested that the biochemical basis of the disease was reduced production of type I collagen. This study was designed to determine if this biochemical finding segregated with the disease within an individual family. Dermal fibroblast strains were established from three generations of a family having the typical features of type I OI. Analysis of the collagenous proteins made in culture revealed an elevated alpha 1(III) to alpha 1(I) collagen type ratio and an elevated alpha 1(I) to alpha 2(I) collagen chain ratio. The procollagen that accumulated in the medium reflected these ratios to the same degree. Total collagen synthesis was significantly reduced in affected family members. Therefore, the most striking abnormality in affected members was a 50-75% reduction of type I collagen production. Furthermore, the ratio of the alpha 1(I)/alpha 2(I) collagen messenger RNA (mRNA), measured by dot hybridization, was one-half of the value of uninvolved family members and unrelated controls. Since the reduction in the production of type I collagen and the altered alpha 1(I)/alpha 2(I) mRNA ratio clearly segregated with affected individuals within this family, these biochemical measurements may be a useful genetic marker for type I OI. PMID- 4031066 TI - Regional alveolar pressure during periodic flow. Dual manifestations of gas inertia. AB - We measured pressure excursions at the airway opening and at the alveoli (PA) as well as measured the regional distribution of PA during forced oscillations of six excised dog lungs while frequency (f[2-32 Hz]), tidal volume (VT [5-80 ml]), and mean transpulmonary pressure (PL [25, 10, and 6 cm H2O]) were varied. PA's were measured in four alveolar capsules glued to the pleura of different lobes. The apex-to-base ratio of PA's was used as an index of the distribution of dynamic lung distension. At low f, there was slight preferential distension of the lung base which was independent of VT, but at higher f, preferential distension of the lung apex was found when VT's were small, whereas preferential distension of the lung base was found when VT's approached or exceeded dead space. These VT-related changes in distribution at high frequencies seem to depend upon the branching geometry of the central airways and the relative importance of convective momentum flux vs. unsteady inertia of gas residing therein, which, in this study, we showed to be proportional to the ratio VT/VD*, where VD* is an index of dead space. Furthermore, they imply substantial alteration in the distribution of ventilation during high frequency ventilation as f, VT, and PL vary. The data also indicate that alveolar and airway opening pressure costs per unit flow delivered at the airway opening exhibit weakly nonlinear behavior and that resonant amplification of PA's, which has been described previously for the case of very small VT's, persists but is damped as VT's approach dead space values. PMID- 4031067 TI - Modulation of phosphate absorption by calcium in the rabbit proximal convoluted tubule. AB - Proximal convoluted (S2) and straight (S3) renal tubule segments were studied to determine the effect of Ca on lumen-to-bath phosphate flux (JlbPO4). Increasing bath and perfusate Ca from 1.8 to 3.6 mM enhanced JlbPO4 from 3.3 +/- 0.7 to 6.6 +/- 0.6 pmol/mm per min in S2 segments (P less than 0.001) but had no effect in S3 segments. Decreasing bath and perfusate Ca from 1.8 to 0.2 mM reduced JlbPO4 from 3.7 +/- 0.6 to 2.2 +/- 0.6 in S2 segments. These effects were unrelated to changes in fluid absorption and transepithelial potential difference. Increasing cytosolic Ca with a Ca ionophore, inhibiting the Ca-calmodulin complex with trifluoperazine, or applying the Ca channel blocker nifedipine had no effect on JlBPO4 in S2 segments. Increasing only bath Ca from 1.8 to 3.6 mM did not significantly affect JlbPO4. However, increasing only perfusate Ca enhanced JlbPO4 from 3.4 +/- 0.7 to 6.1 +/- 0.7 pmol/mm per min (P less than 0.005). Inhibition of hydrogen ion secretion, by using a low bicarbonate, low pH perfusate, both depressed base-line JlbPO4 and abolished the stimulatory effect of raising perfusate Ca. Net phosphate efflux (JnetPO4) also increased after ambient calcium levels were raised, ruling out a significant increase in PO4 backflux. When net sodium transport was abolished by reducing the bath temperature to 24 degrees C, JnetPO4 at normal ambient calcium was reduced and increasing ambient calcium failed to increase it, ruling out a simple physicochemical reaction wherein phosphate precipitates out of solution with calcium. The present studies provide direct evidence for a stimulatory effect of Ca on sodium-dependent PO4 absorption in the proximal convoluted tubule, exerted at the luminal membrane. It is postulated that Ca modulates the affinity of the PO4 transporter for the anion. PMID- 4031068 TI - Induction of the insulin proreceptor by hydrocortisone in cultured lymphocytes (IM-9 line). AB - Hydrocortisone increases the number of insulin receptors at the surface of human cultured lymphocytes (IM-9 line) without altering the degradation of the mature receptor subunits. To elucidate the effect of glucocorticoids on the biosynthesis of the insulin receptor of IM-9 cells, we preincubated cells in the presence or absence of hydrocortisone (1.4 X 10(-6) M) and measured the incorporation of radiolabeled sugars into the insulin receptor components. From 6 to 22 h, there was a progressive increase in the incorporation of [3H]mannose into the insulin proreceptor (190,000 mol wt) and the mature subunits (210,000, 135,000, and 95,000 mol wt). The amount incorporated into hydrocortisone-treated cells was always three to four times higher than in control cells, despite no change in cell number, viability, or radioactive sugar pool. To test directly the earliest effect of hydrocortisone, we undertook pulse-chase studies. The incorporation of [3H]mannose into the insulin receptor precursor and the mature subunits was detectable as early as 30 min of chase and was two to three times higher in hydrocortisone-treated cells at any time point of incubation. In both groups, the increase into the proreceptor (190,000 mol wt) peaked by 60 min and decreased rapidly thereafter (half disappearance rate, 45 min); there was a sustained increase of incorporation into the two major mature subunits (135,000 and 95,000 mol wt) throughout the 4-h chase. Hydrocortisone represents the first pharmacologic agent shown to induce the synthesis of the insulin proreceptor. Further, we present a model system designed to study other agents that may act at a very early step in insulin receptor biosynthesis. PMID- 4031069 TI - Biosynthesis of bile acids in cerebrotendinous xanthomatosis. Relationship of bile acid pool sizes and synthesis rates to hydroxylations at C-12, C-25, and C 26. AB - To examine the defect in side-chain oxidation during the formation of bile acids in cerebrotendinous xanthomatosis, we measured in vitro hepatic microsomal hydroxylations at C-12 and C-25 and mitochondrial hydroxylation at C-26 and related them to the pool size and synthesis rates of cholic acid and chenodeoxycholic acid as determined by the isotope dilution technique. Hepatic microsomes and mitochondria were prepared from seven subjects with cerebrotendinous xanthomatosis and five controls. Primary bile acid synthesis was markedly reduced in cerebrotendinous xanthomatosis as follows: cholic acid, 133 +/- 30 vs. 260 +/- 60 mg/d in controls; and chenodeoxycholic acid, 22 +/- 10 vs. 150 +/- 30 mg/d in controls. As postulated for chenodeoxycholic acid synthesis, mitochondrial 26-hydroxylation of 5 beta-cholestane-3 alpha, 7 alpha-diol was present in all specimens and was 30-fold more active than the corresponding microsomal 25-hydroxylation. However, mean mitochondrial 26-hydroxylation of 5 beta-cholestane-3 alpha,7 alpha-diol was less active in cerebrotendinous xanthomatosis than in controls: 59 +/- 17 compared with 126 +/- 21 pmol/mg protein per min. As for cholic acid synthesis, microsomal 25-hydroxylation of 5 beta-cholestane-3 alpha,7 alpha,12 alpha-triol was substantially higher in cerebrotendinous xanthomatosis and control preparations (620 +/- 103 and 515 +/- 64 pmol/mg protein per min, respectively) than the corresponding control mitochondrial 26-hydroxylation of the same substrate (165 +/- 25 pmol/mg protein per min). Moreover in cerebrotendinous xanthomatosis, mitochondrial 5 beta cholestane-3 alpha,7 alpha,12 alpha-triol-26-hydroxylase activity was one-seventh as great as in controls. Hepatic microsomal 12 alpha-hydroxylation, which may be rate-controlling for the cholic acid pathway, was three times more active in cerebrotendinous xanthomatosis than in controls: 1,600 vs. 500 pmol/mg protein per min. These results demonstrate severely depressed primary bile acid synthesis in cerebrotendinous xanthomatosis with a reduction in chenodeoxycholic acid formation and pool size disproportionately greater than that for cholic acid. The deficiency of chenodeoxycholic acid can be accounted for by hyperactive microsomal 12 alpha-hydroxylation that diverts precursors into the cholic acid pathway combined with decreased side-chain oxidation (mitochondrial 26 hydroxylation). However, side-chain oxidation in cholic acid biosynthesis may be initiated via microsomal 25-hydroxylation of 5beta-cholestane 3alpha,7alpha,12alpha-triol was substantially lower in control and cerebrotendinous xanthomatosis liver. Thus, separate mechanisms may exist for the cleavage of the cholesterol side chain in cholic acid and chenodeoxycholic acid biosynthesis. PMID- 4031070 TI - Markedly increased circulating pyridoxal-5'-phosphate levels in hypophosphatasia. Alkaline phosphatase acts in vitamin B6 metabolism. AB - Markedly increased circulating concentrations of pyridoxal-5'-phosphate (PLP) were found in each of 14 patients representing all clinical forms of hypophosphatasia, an inborn error characterized by deficient activity of the tissue nonspecific (bone/liver/kidney) isoenzyme of alkaline phosphatase (AP). The mean PLP concentration in plasma was 1174 nM (range, 214-3839 nM) in the patients and 57 +/- 26 nM (mean +/- SD) in 38 control subjects. In four affected children, urinary excretion of the PLP degradation product, 4-pyridoxic acid, was unremarkable during consumption of normal quantities of dietary vitamin B6. Our findings identify increased circulating PLP concentration as a marker for hypophosphatasia and provide further evidence that tissue nonspecific AP acts in vitamin B6 metabolism. Tissue nonspecific AP appears to function as an ectoenzyme to regulate extracellular but not intracellular levels of PLP substrate. Performing assays of circulating PLP concentration alone to assess vitamin B6 nutrition may be misleading in disorders associated with altered AP activity. PMID- 4031071 TI - Substrate cycling between gluconeogenesis and glycolysis in euthyroid, hypothyroid, and hyperthyroid man. AB - Substrate, or futile cycles, have been hypothesized to be under hormonal control, and important in metabolic regulation and thermogenesis. To define the role of thyroid hormones in the regulation of substrate cycling in glycolysis and gluconeogenesis, we measured rates of cycling in normal (n = 4), hypothyroid (n = 5), and hyperthyroid (n = 5) subjects employing a stable isotope turnover technique. Glucose labeled with deuterium at different positions (2-D1-, 3-D1-, and 6,6-D2-glucose) was given as a primed-constant infusion in tracer doses, and arterialized plasma samples were obtained and analyzed by gas-chromatography mass spectrometry for the steady state enrichment of glucose that was labeled at the various positions. The rate of appearance (Ra) was then calculated for each isotopic tracer. The difference between the Ra determined by 2-D1-glucose (Ra2) and the Ra determined by 3-D1-glucose (Ra3) represents the substrate cycling rate (SCR) between glucose and glucose-6-phosphate. The difference between the Ra determined by 3-D1-glucose (Ra3) and the Ra determined by 6,6-D2-glucose (Ra6) represents the SCR between fructose-6-phosphate and fructose-1,6-diphosphate. The difference between Ra2 and Ra6 represents the combined SCR of both cycles. In normal subjects (serum thyroxine [T4] = 8.4 +/- 1.2 microgram/dl (all expressions, mean +/- SD), n = 4), the rates of appearance for Ra2, Ra3, and Ra6 were 3.23 +/- 0.56, 2.64 +/- 0.50, and 2.00 +/- 0.27 mg/kg X min, respectively, whereas those in the hypothyroid subjects (T4 = 1.0 +/- 0.8 microgram/dl; n = 5) were 1.77 +/- 0.56 (P less than 0.01), 1.52, 1.57 +/- 0.31 (P less than 0.05) mg/kg X min, respectively. Conversely, the rates of appearance for Ra2 and Ra6 in the hyperthyroid subjects (T4 = 23.9 +/- 3.6 micrograms/dl) were 3.94 +/- 0.43 (P less than 0.05) and 2.54 +/- 0.22 (P less than 0.02), respectively, compared with the normal subjects. On the basis of these data, we noted that the normal subjects had a combined SCR of 1.23 +/- 0.35 mg/kg X min. In contrast, the hypothyroid patients had a significantly decreased combined SCR, 0.20 +/- 0.54 mg/kg X min (P less than 0.02). The hyperthyroid patients had a combined SCR of 1.39 +/- 0.23 mg/kg X min (P less than NS). To determine whether these cycles responded to thyroid hormone treatment, these same hypothyroid subjects were acutely treated for 1 wk with parenteral 50 micrograms/d sodium L triiodothyronine and chronically with 100-150 micrograms/d L-thyroxine. After 7 d, their mean oxygen consumption rate and carbon dioxide production rate increased significantly from 102+/-13 micromol/kg.min, to 147+/-34 micromol/kg.min (P<0.05), and from 76+/-13 micromol/kg.min to 111+/-19 micromol/kg.min (P<0.05), respectively. The combined SCR (Ra(2)--Ra(6) remained unchanged at 0.07+/-0.37 mg/kg.min. However, after 6 mo of oral L-thyroxine therapy (T(4)=9.5+/-1.4 microgram/kl) the treated hypothyroid patients had increased their combined SCR (Ra(2)--Ra(6)) to 0.86 +/-0.23 mg/kg.min (P<0.02), a value not significantly different from the combined SCR of normal subjects. We conclude that substrate cycling between glucose and glucose-6-phosphate and between fructose-6-phosphate and fructose-1,6-diphosphate occurs in man and is affected by thyroid hormone. Substrate cycles may represent a mechanism by which thyroid hormone alters the sensitivity of certain reactions to metabolic signals. PMID- 4031072 TI - Effect of arginine vasopressin on renal medullary blood flow. A videomicroscopic study in the rat. AB - The role of arginine vasopressin (AVP) in the regulation of renal medullary blood flow is uncertain. To determine if AVP has a direct vasoconstrictive action on vasa recta, the effect of AVP on erythrocyte velocity (VRBC), diameter, and blood flow (QVR) in descending vasa recta (DVR) and ascending vasa recta (AVR) was studied in the exposed renal papilla of four groups of chronically water diuretic rats using fluorescence videomicroscopy. There were three periods: control (period 1), experimental (period 2), and recovery (period 3). In periods 1 and 3, all groups received hypotonic saline. In period 2, group I rats (AVP) received AVP (45 ng/h per kg body wt); group II (time) received hypotonic saline alone; group III (AVP plus V1-inhibitor) received AVP plus its vascular antagonist, d(CH2)5Tyr(Me)AVP; and group IV (V1-inhibitor) received the vascular antagonist alone. Another group of rats (group V) was employed to demonstrate that the rise in blood pressure induced by a 3- or 10-ng/kg injection of AVP was virtually abolished by the prior infusion of the V1-inhibitor. The urine of group III as well as group I rats was concentrated (Uosm = 721 +/- 62 H2O vs. 670 +/- 39 mosM/kg), while urine remained dilute in groups II and IV. In period 2, VRBC and QVR in DVR and AVR decreased in group I, did not decrease in group III, and increased in groups II and IV. The vascular antagonist thus completely abolished the AVP-induced decrease in QVR in group III. These findings unequivocally establish that AVP in physiological amounts reduces medullary blood flow, at least in part, by a direct vasoconstrictive action on the medullary microcirculation. They also show that an effect of AVP on medullary blood flow is not necessary for its antidiuretic effect. PMID- 4031073 TI - Effect of Reye's syndrome serum on isolated chinchilla liver mitochondria. AB - A general impairment of liver mitochondrial enzymes is central to Reye's syndrome (RS). The respiration of isolated liver mitochondria was measured after the addition of concentrated normal serum or RS serum derived from 12 patients. RS serum stimulates oxygen consumption in isolated rat liver mitochondria. This effect is due to the oxidation of uric acid by peroxisomes contaminating the preparation and a stimulation of mitochondrial respiration (1.05 +/- 0.14 nmol of O2/min X mg of protein; control 0.30 +/- 0.08 nmol O2/min X mg). The stimulation of respiration occurs in the presence of all respiratory substrates, is dependent on the amount of serum added, and represents an uncoupling of oxidative phosphorylation. RS serum reduces ATP formation by 15-76%. The uncoupling effect correlates with the amount of free fatty acid in the serum sample and resembles the effect induced by the addition of a dicarboxylic fatty acid. Dicarboxylic fatty acids, especially long-chain dicarboxylic acids, impair ATP formation. Dicarboxylic acids were found in the serum of all RS patients and comprised as much as 54% of the total serum free fatty acids. 90% of the serum dicarboxylic acids were of 16-18 carbon lengths. The amount of dicarboxylic acids in the RS serum corresponded directly with the reduction in ATP formation by the RS serum. This demonstrates that dicarboxylic acids occur in RS and may be important in the general impairment of mitochondrial function in RS and other disorders where they are present. PMID- 4031074 TI - Contribution of individual superficial nephron segments to ammonium handling in chronic metabolic acidosis in the rat. Evidence for ammonia disequilibrium in the renal cortex. AB - Ammonia entry along surface nephron segments of rats was studied with micropuncture techniques under control and chronic metabolic acidosis conditions. Tubule fluid was collected successively from sites at the end and beginning of the distal tubule and at the end of the proximal tubule of the same nephron. During chronic metabolic acidosis, ammonium excretion doubled. As anticipated, the ammonium concentration (TFNH+4) was significantly higher in proximal tubule fluid during acidosis, and ammonium delivery to end proximal sites increased from 19.4 +/- 2.3 to 34.0 +/- 3.2 pmol/min (P less than 0.001). Although chronic acidosis did not affect TFNH+4 at the beginning of the distal tubule, ammonium delivery to the end of the distal tubule increased from 5.72 +/- 0.97 to 9.88 +/- 0.97 pmol/min. In both control and acidotic groups ammonium delivery was lower (P less than 0.001) to end distal sites than to end proximal sites, indicating net loss in the intervening segment. This loss was greater during chronic metabolic acidosis (23.9 +/- 3.3 vs. 13.6 +/- 2.0 pmol/min in controls, P less than 0.025). In both groups net entry of ammonia, in similar amounts, occurred along the distal tubule (P less than 0.05). In situ pH averaged 6.80 +/- 0.05 at end proximal tubule sites and fell to 6.54 +/- 0.08 at the beginning of the distal tubule (P less than 0.005). Chronic metabolic acidosis did not affect these measurements. The calculated free ammonia at the end of the proximal tubule rose from 9.3 +/- 2.2 to 21 +/- 9 microM (P less than 0.005) during chronic metabolic acidosis, and was also higher at beginning distal sites during acidosis (8.8 +/- 2.4 vs. 2.7 +/- 0.7 microM in controls, P less than 0.05). In both groups ammonia values for the beginning distal tubule fluid were lower than for end proximal tubule fluid. Thus, loss of ammonium in the loop segment is enhanced by chronic metabolic acidosis. Distal entry of ammonia is markedly less than along the proximal tubule and does not change in chronic metabolic acidosis, and ammonia permeabilities for the proximal and distal segments of surface nephrons seem different. PMID- 4031076 TI - Coming of age: developmental pediatrics in the late twentieth century. PMID- 4031075 TI - Metabolic effect of 3,3',5'-triiodothyronine in cultured growth hormone-producing rat pituitary tumor cells. Evidence for a unique mechanism of thyroid hormone action. AB - Physiologic levels of 3,3',5'-triiodothyronine (rT3) are generally believed to have minimal metabolic effects in the pituitary gland and other tissues. In the present studies, the regulatory role of rT3 and other thyroid hormones on iodothyronine 5'-deiodinase (I5'D) activity was studied in a growth hormone producing rat pituitary tumor cell line (GH3 cells). I5'D activity was thiol dependent and displayed nonlinear reaction kinetics suggesting the presence of two enzymatic processes, one having a low Michaelis constant (Km for thyroxine [T4] of 2 nM) and a second with a high Km value (0.9 microM). Growth of cells in hormone-depleted medium resulted in a two- to 3.5-fold increase in low Km I5'D activity (P less than 0.001). The addition of thyroid hormones to the culture medium resulted in a rapid, dose-dependent inhibition of low Km I5'D activity with the following order of analogue potency: rT3 greater than or equal to T4 greater than 3,5,3'-triiodothyronine (T3). Using serum-free culture conditions, rT3 was approximately 50 times more active than T3. These inhibitory effects were noted within 15 min of hormone addition and could not be attributed to substrate competition with T4. These findings suggest that the control of T4 to T3 conversion by thyroid hormones in the anterior pituitary gland is mediated by a unique cellular mechanism that is independent of the nuclear T3 receptor; and under some circumstances, rT3 may play a regulatory role in controlling this enzymatic process. PMID- 4031077 TI - What is the science base for behavioral pediatrics? PMID- 4031078 TI - The role of the pediatrician in the delivery of behavioral services. PMID- 4031080 TI - Critical issues in behavioral pediatric training. PMID- 4031079 TI - Behavioral pediatrics: interaction with other disciplines. PMID- 4031081 TI - Comments on teaching developmental pediatrics and behavioral pediatrics. PMID- 4031082 TI - Behavioral pediatrics in the examinations of the American Board of Pediatrics. PMID- 4031083 TI - Blood-injury-illness phobia: a review. AB - The empirical literature that pertains to phobias of blood, injury, or illness (BII) is surveyed. BII phobia is selectively associated with a vasovagal fainting response upon exposure to phobic stimuli, and the clinical entity may represent an exaggeration of a response that is relatively prevalent in the general population. Clinical, demographic and etiological information obtained from a series of 15 BII phobics is presented, and the suggestion is made that this disorder warrants a diagnostic category separate from simple phobia. PMID- 4031084 TI - Ethnicity and life event cognitive appraisals and experiences. AB - This study compared the cognitive appraisals and incident ratings of urban American Indians (N = 50), Anglo-Americans (N = 50), and Hispanics (N = 47) on a revised version of the Social Readjustment Rating Scale (SRRS). Results indicated no overall significant differences among the three ethnic groups. However, on comparison of individual life events items, the groups differed significantly on the cognitive appraisal of 8 items and on the incidence of 10 items. Of these items, only 2 overlapped between cognitive appraisals and actual incidence. Results are discussed in terms of potential use of the revised SRRS with these ethnic groups in future research on the relationship between life events and physical and psychological disorders. PMID- 4031085 TI - Affective disorders and depression as measured by the Diagnostic Interview Schedule and the Beck Depression Inventory in an unselected adult population. AB - Rates, demographic correlates, and differential symptomatic expression as a function of gender of affective disorders and depression as measured by the Diagnostic Interview Schedule (DIS) and the Beck Depression Inventory (BDI) were examined in 298 paid adult volunteers selected by the random digit dialing method. According to the DIS, 7.7% were diagnosed as current affective disorder, 6% as current primary unipolar depression, 23.5% as lifetime affective disorder, and 19.5% as lifetime primary unipolar depression. According to the BDI, 19.8% scored depressed: 10.7% as mildly, 5.0% moderately, and 4.0% severely depressed, respectively. Of 11 demographic variables whose relation to DIS diagnoses were examined in a multivariate context, only occupation was correlated significantly with current primary unipolar depression. Of the same variables whose relation to BDI score was examined, education and race were correlated significantly with BDI score. There was no evidence of differential symptomatic expression as a function of gender as measured by lifetime diagnosis of primary unipolar depression on the DIS. PMID- 4031086 TI - The Unpleasant Events Schedule: a scale for the measurement of aversive events. AB - This paper reports reliability and validity data on the Unpleasant Events Schedule (UES), a 320-item scale that assesses stressful life events. The UES assesses both the frequency and aversiveness of events within a 1-month time frame. Rational, empirical, and factorial scales were derived from the UES. Of these, nine scales were retained that were mutually independent, demonstrated good internal reliability, and tapped various dimensions of clinical interest. A short 53-item form of the UES also was developed. The UES correlated moderately (r = .37) with depression. A discriminant analysis revealed that the UES contributed significantly above and beyond scores on the PES (MacPhillamy & Lewinsohn, 1982) to the proportion of variance in discriminating depressed from nondepressed subjects. PMID- 4031087 TI - Psychological assessment in chronic pain. AB - Assessment of psychological status in chronic pain patients is an important aspect of evaluation and treatment in pain management programs. Unfortunately, most of the psychological tests used in common practice have not been used extensively with chronic pain patients. Normative and comparative data must be generated to allow for valid and efficient psychometric assessment. The present paper is a preliminary comparison of several instruments of potential usefulness in the assessment of anxiety and depression among pain patients (N = 34). The SCL 90-R appeared to offer the best combination of relevant data and efficient assessment. However, it was noted that there were significant intercorrelations among the SCL-90-R subscales, which suggests a unitary factor structure. PMID- 4031088 TI - Interrelationships of locus of control content dimensions and hopelessness. AB - Items from three locus of control (LOC) tests and the Beck Hopelessness Scale were administered to 197 college students. Factor analyses produced multiple factors for each LOC test, but the Beck scale proved to be unidimensional. Factor scales were constructed for each test, and scores were factor analyzed to discover common content. Each LOC test contained a salient dimension that described belief in luck, chance, or fate, and corresponding scales were well correlated. Internal control was the second common theme, with variations according to whether control was attributed to oneself or to people in general. The third common component expressed a personal helplessness or powerlessness. Each common factor was loaded by the Hopelessness Scale, which also correlated with all but one LOC factor scale. PMID- 4031089 TI - Memory span and long-term memory deficits in brain-impaired patients. AB - Measures of verbal and visuospatial memory span and long-term memory were obtained from 21 brain-impaired and 21 neurologically unimpaired Veterans Administration medical patients. Significant deficits in both memory span and long-term memory were observed in the brain-impaired patients. Contrary to predictions from the experimental literature, memory span tests that require more processing of item content and location were not superior in detecting the memory span deficits. Discriminant function analyses revealed that measures of verbal and visuospatial long-term memory provided unique discrimination between the brain-impaired and unimpaired patients. However, when memory span measures were analyzed alone, inclusion of more than one measure of memory span did not provide additional unique discrimination. Implications for the clinical assessment of memory functioning are discussed. PMID- 4031090 TI - The relationship of age to performance on the Luria-Nebraska Neuropsychological Battery. AB - The effect of age upon the Luria-Nebraska Neuropsychological Battery (LNNB) was studied by administering the LNNB and the Wechsler Adult Intelligence Scale to three groups of subjects: A group aged 17-30, a group aged 50-55, and a group aged 65 and older. No subject had any history of brain pathology or psychotic emotional disturbance. Two of the Luria-Nebraska subtests, the Motor and Visual, showed a significant sex-effect in that males performed better than females. Age was related significantly to performance on 11 of 16 Luria Nebraska subscales; older subjects rather consistently showed poorer performance than younger subjects. When intelligence (i.e., Wechsler IQs) and education were controlled statistically, partial correlations still revealed that age had significant effects upon 13 of 16 Luria-Nebraska subscales. These results closely parallel earlier data that concern age-effects on the Luria-Nebraska Battery. PMID- 4031091 TI - Test-retest stability of the WAIS-R in a clinical sample. AB - This study assessed WAIS-R test-retest stability for a sample of 21 psychiatric and neurological patients. The test-retest interval ranged from 2 weeks to 144 weeks, with a mean of 38 weeks. Subtest stability coefficients were highly significant; only Similarities, r(19) = .45, p less than .05, fell below a correlation of .74. The Verbal, Performance, and Full Scale IQs yielded highly significant stability coefficients (.79, .88, and .86). Nevertheless, the range of gain or loss for any single individual was comparatively large. On the Full Scale IQ, 18 of 21 (86%) subjects showed changes of 3 points or more, and 8 of 21 (38%) actually changed IQ classifications. Gain or loss in total score was unrelated to initial level of brightness on the Full Scale, age at initial testing, or days between examinations. Conversely, gain or loss on the Full Scale was associated strongly with years of education, r(19) = .55, p less than .01. When the sample was divided into brain-damaged and psychiatric subgroups, the difference in retest gain on the Full Scale IQ was nonsignificant. PMID- 4031092 TI - The specificity of childhood problem behavior for adolescent and young adult maladjustment. AB - A longitudinal sample of 1130 low peer choice grade school children were followed through record sources into young adulthood. Specific childhood problem behavior clusters were examined in relationship to delinquency, adult criminality, and mental health treatment contact. Childhood aggression, in the context of peer rejection, was related significantly to delinquency for males, an antisocial diagnosis for both sexes, and differentiated subjects in the judicial system from those in the mental health system. A childhood "neurological" scale differentiated subjects with a schizophrenic spectrum diagnosis from other subjects with mental health treatment. PMID- 4031093 TI - Diagnosis and childhood firesetting. AB - This paper presents findings on the relationship of childhood firesetting and DSM III diagnosis in a representative sample of child psychiatric outpatients (N = 204). Childhood firesetting and the DSM-III diagnosis of conduct disorder are strongly related; they show a significant interaction effect with lessened competence as measured by activities and increased externalizing (undercontrolled) behavior. PMID- 4031094 TI - Smoking cessation in chronically ill medical patients. AB - Eight male smokers with chronic pulmonary and/or cardiac disease participated in a 9-week treatment program that consisted of gradual nicotine withdrawal, self management techniques, and relapse prevention strategies. At 1-year follow-up, 50% remained abstinent, while those who relapsed were smoking substantially less than prior to treatment. Reductions in CO and thiocyanate levels were both statistically significant and clinically meaningful. Nonspecific factors of group influence and support, as well as weekly feedback of CO levels, were judged as particularly important components of treatment. The availability of non-aversive strategies for smoking cessation in persons with chronic illness is important. These promising though preliminary findings indicate the need for additional applications of multi-component behavioral approaches with this population. PMID- 4031095 TI - Comment on "Religiosity and United States suicide rates, 1972-1978". AB - This article comments on the Martin article on religiosity and suicide rates in the United States. Specifically, it is pointed out by the present author that Martin's data do not allow him to draw the conclusions that he offered in his article. A correlational study does not allow for cause and effect conclusions, and the use of group data precludes conclusions about individual cases. PMID- 4031096 TI - Role of immunohistochemistry in diagnosis of nasopharyngeal tumours. AB - To evaluate the usefulness of immunocytochemistry in the differential diagnosis of nasopharyngeal tumours, 35 undifferentiated nasal carcinomas were examined with a panel of monoclonal antibodies against a wide variety of epithelial and non-epithelial antigens. The results were compared with those obtained from a series of nasopharyngeal tumours comprising three squamous cell carcinomas, six lymphomas, one rhabdomyosarcoma, and one yolk sac tumour. All of the carcinomas were positive with at least one of the antiepithelial markers and negative for the leucocyte common antigen and were clearly distinguishable from the nasopharyngeal lymphomas, which gave the opposite staining pattern. It was concluded that such a panel of monoclonal antibodies would be extremely useful for the differential diagnosis of nasopharyngeal tumours, particularly with small or technically inadequate biopsies. PMID- 4031097 TI - Acquired cystic disease of kidney with multiple renal and urothelial neoplasms. AB - Acquired polycystic disease with concurrent development of renal cell tumours is a well documented complication of long term haemodialysis. We present a case of acquired polycystic disease with renal cell tumours and multifocal urothelial tumours. Only two similar cases have been recorded. PMID- 4031098 TI - Clinicopathological importance of deposits of amyloid in the femoral head. AB - The pattern of amyloid deposits in the femoral head is described in four cases, two of which had deposits of amyloid related to age and two of which had generalised systemic amyloidosis (one of primary amyloidosis, one of multiple myeloma). The deposition of amyloid in the articular cartilage of the femoral head was similar in all four cases. Heavy deposits of synovial amyloid were identified in the case with primary amyloidosis and in one of the cases with amyloidosis related to age. Both cases of generalised systemic amyloidosis showed abundant deposits of amyloid in the bone marrow. Amyloid was not present in the bone marrow of either case with amyloidosis related to age. The importance of these findings is discussed in relation to the pathogenesis of the arthropathy syndrome of a rheumatoid type described in cases of primary amyloidosis and multiple myeloma. PMID- 4031099 TI - Aortic valvular tophus: identification by X-ray diffraction of urate and calcium phosphates. AB - A typical gouty tophus with birefringent, dichroic, needle shaped crystals was found in a resected calcified aortic valve on routine histological examination. The patient, an elderly man, had a long history of gout. X-ray diffraction confirmed the presence of sodium acid urate monohydrate and identified hydroxyapatite and whitlockite in the accompanying dystrophic calcification of the aortic valves. Previous reports indicate that gouty tophi of the cardiac valves are rare: of the nine cases reported, eight occurred in the mitral valve. PMID- 4031100 TI - Hepatic pseudolipoma. AB - Pseudolipoma of the liver is a rare condition which may be confused with metastatic tumours, primary tumours, or other lesions of the liver. This study presents three hepatic pseudolipomas that occurred in men aged 33, 38, and 42 years. The prevalence of hepatic pseudolipomas was 0.2% in a series of 1300 consecutive necropsies. The histological elements of pseudolipoma are identical with those of twisted peritoneal fat nodules (epiploic appendix) or peritoneal loose bodies, four cases of which were also found in the same material. The size of the migrating loose body may be the critical factor for entry into the space between the diaphragm and the liver. The nutrition of one pseudolipoma seemed to have been obtained from the liver capsule. There was no significant correlation with previous abdominal surgery or obesity. PMID- 4031101 TI - Clear cell carcinoma of the lung. AB - Six tumours of the lung initially classified as clear cell carcinoma, were studied. Examination of further material by light and electron microscopy showed adenocarcinomatous differentiation in three cases and squamous differentiation in two. One case showed the features of a large cell anaplastic carcinoma. The clear appearance of the cytoplasm in paraffin sections was due to accumulations of glycogen that were partially removed during processing. It is concluded that clear cell carcinoma is not a single and separate entity. PMID- 4031102 TI - Morphometry of blood monocytes in malignant lymphoma. AB - Morphometric methods were used to study the ultrastructure of blood monocytes in 23 patients with Hodgkin's disease, 12 patients with non-Hodgkin's lymphoma, and 20 normal subjects. The results were analysed using both univariate and multivariate methods. Both analyses supported the interpretation that the total mitochondrial contribution to the cellular ultrastructure was less in Hodgkin's disease than in the other two groups, with smaller mitochondrial volume fractions, volumes, and surface areas being found. In the patients with non Hodgkin's lymphoma univariate analysis suggested that monocyte nuclei were larger, with more euchromatin and a relatively smaller heterochromatin euchromatin interface; the cell profile area was larger and the surface to volume ratio was smaller compared with normal subjects. Morphological changes have not previously been described in blood monocytes in malignant lymphoma, but they may be the counterpart of the known mononuclear phagocyte dysfunction. PMID- 4031103 TI - Enzyme linked direct antiglobulin tests in patients with autoimmune haemolysis. AB - Enzyme linked and agglutination direct antiglobulin tests were carried out on blood samples from 219 patients suspected of having autoimmune haemolysis. The enzyme linked tests were more sensitive: they could detect the small amounts of IgG, IgA, and IgM which are normally present on red cells and showed increased amounts of cell bound immunoglobulins in patients with Coombs test negative autoimmune haemolysis. Many patients had immunoglobulins of more than one class bound to their red cells; considering the degree of haemolysis in individual patients, it appeared that the different immunoglobulin classes acted synergistically in effecting red cell destruction, even in amounts too small to be detected by the agglutination tests. In patients with cold reacting autoantibodies and complement coating of the red cells active haemolysis was found (with one exception) where IgM was detected on the cells by the enzyme linked method. Elution studies indicated that immunoglobulins detected just by the enzyme linked techniques were red cell antibodies. Both enzyme linked and agglutination tests were negative in 66 patients: 61 of these had no evidence of haemolysis, and in the other five the haemolysis was not autoimmune in origin. PMID- 4031104 TI - Electron microscopic studies of human haemosiderin and ferritin. AB - Ferritin and haemosiderin were isolated from fresh frozen human spleens that had been removed from patients with secondary iron overload due to multiple transfusions. Haemosiderin was solubilised by a novel technique that maintains its integrity. Unstained preparations of haemosiderin and ferritin were visualised and quantitative measurements made of the volumes of iron core. The mean diameter of the ferritin core (6.4 nm) was larger than that of haemosiderin (5.7 nm). In addition, haemosiderin, in contrast to ferritin, showed a large number of cores of less than 5 nm in diameter. Negatively stained preparations of haemosiderin and ferritin were visualised, confirming the small core size of the haemosiderin. The protein shell of haemosiderin, unlike that of ferritin, was thinner and irregular. These findings are consistent with the suggestion that haemosiderin is derived from ferritin by partial proteolysis and partial solubilisation of the iron core, presumably by lysosomal action. PMID- 4031105 TI - Indifferent streptococci in normal and purulent eyes of neonates. AB - The incidence of indifferent streptococci in the eyes of neonates less than 6 days old was investigated. The isolation of indifferent streptococci was significantly higher in infants with sticky eyes. Speciation using a shortened identification scheme was carried out on isolates; Streptococcus mitior and Streptococcus sanguis were the most common species in both purulent and non infected eyes. Streptococcus mutans, a species not normally found in edentulous infants, comprised 14% of indifferent streptoccoi from neonates with sticky eyes but only 1% of those from infants with non-purulent eyes. It is suggested that the role of indifferent streptococci in neonatal conjunctivitis will be resolved only if speciation is performed. PMID- 4031107 TI - Growth of staphylococci on nutrient agar at low temperature. PMID- 4031106 TI - Microbial and metabolic profile of achlorhydric stomach: comparison of pernicious anaemia and hypogammaglobulinaemia. AB - The microbial flora and some of its metabolites and enzymes in the stomach were compared in patients with achlorhydria, pernicious anaemia, and primary hypogammaglobulinaemia and in patients with dyspepsia with normal gastric acidity. Detailed analysis of the flora of the gastric juice and of the mucosa from the antrum, body, and fundus in six patients with hypogammaglobulinaemia (mean pH 8.2), seven patients with pernicious anaemia (mean pH 7.3), and five patients with dyspepsia (mean pH 1.9) yielded 22 different genera of bacteria, mainly from the patients with achlorhydria, the most common being streptococci, micrococci, staphylococci, veillonella, and lactobacilli. A similar flora was found associated with the mucosa at all three sites. Various metabolites were also looked for. beta Glucoronidase and C14 lipase were found in patients with hypogammaglobulinaemia but not in those with pernicious anaemia or dyspepsia. Volatile fatty acids were not found. Relatively high concentrations of ethanol were found in the patients with hypogammaglobulinaemia compared with those with pernicious anaemia (p = 0.02). Similar concentrations of dimethylamine were found in all three groups, but the concentrations of trimethylamine were much higher in patients with pernicious anaemia and hypogammaglobulinaemia. The high concentrations of some microbial enzymes and ethanol differentiated the group with hypogammaglobulinaemia from the rest, and these may bear some relation to the high incidence of gastric cancer in patients with hypogammaglobulinaemia. PMID- 4031108 TI - Is the ratio of total cholesterol to albumin useful as a predictor for the risk of coronary heart disease? PMID- 4031109 TI - Indenolol: a new antihypertensive agent: efficacy, toxicity, and hemodynamic effects in a crossover double-blind study with metoprolol. AB - The antihypertensive efficacy of a new agent, indenolol, was compared with that of the well-established antihypertensive drug, metoprolol, and its hemodynamic effects were investigated using echocardiography. Eighteen hypertensives completed a double-blind, crossover, randomized study using indenolol and metoprolol. Two four-week courses with indenolol or metoprolol were preceded and followed by a two-week placebo period; the total duration of the study was 14 weeks. Indenolol proved to be significantly more effective than metoprolol in decreasing blood pressure values at rest (P less than .05). Furthermore, three patients that failed with metoprolol were successfully treated with indenolol. Both drugs induced a significant decrease in cardiac output that was mediated mainly through a reduction in heart rate, because stroke volume, left ventricle circumferential fiber shortening velocity, and ejection fraction were not significantly reduced by either drug. However, after indenolol, a significant direct relationship was found between the basal values of both cardiac output (r = .809) and total peripheral resistance (r = .800), and the reduction of these parameters. On the contrary, after metoprolol only, the correlation between the basal value of cardiac output and its reduction was significant (r = .790). PMID- 4031110 TI - Indenolol pharmacokinetics and pharmacodynamics after single and repeated daily doses. AB - The relationship between indenolol (an investigational agent) plasma levels and the drug's effect on blood pressure and heart rate was investigated after single and repeated once daily administration at two dosage levels (60 mg and 120 mg) in two different groups of patients with first or second stage hypertension, according to the World Health Organization classification. The pharmacokinetic data were indicative of a first order absorption-elimination curve; time of maximum plasma levels was 1.5 to two hours, and elimination half-life was four hours. The drug did not accumulate in the central compartment after repeated administrations. A long-lasting decrease of both resting and isometric exercise systolic pressure values was recorded after acute indenolol administration. Diastolic pressure was affected only by repeated administrations. The lower dose (60 mg daily) of indenolol did not affect heart rate, whereas the higher dose (120 mg daily) decreased this parameter. A steady state of pressure values and heart rate was reached after 14 days of once daily treatment. PMID- 4031111 TI - A dose-titration trial of guanadrel as step-two therapy in essential hypertension. AB - The efficacy and safety of low-dose guanadrel sulfate were evaluated in 20 patients with essential hypertension based on seated diastolic blood pressures (SDBP) ranging from 95 to 115 mm Hg despite a trial dosage of hydrochlorothiazide 50 mg/d for up to five weeks. These patients had been resistant to, or intolerant of, one or more step-two antihypertensive drugs in the past (i.e., methyldopa, beta-adrenergic blocking agents, clonidine, or prazosin). The majority of patients demonstrated a satisfactory response (SDBP 95 mm Hg or reduction in SDBP of 10 mm Hg) to guanadrel. Nine patients responded at a low dosage, 10 to 20 mg/d and remained free from adverse effects throughout the study (up to 12 weeks of treatment). Of the remaining 11 patients titrated to higher dosages of guanadrel (30 to 60 mg/d), three had no discernible response while six developed adverse effects. The results of the study suggest that guanadrel has an acceptable benefit-to-risk ratio only when used in low dosages (10 to 30 mg/d) and may be successfully employed as step-two antihypertensive therapy in patients resistant to, or intolerant of, other step-two agents. PMID- 4031112 TI - A steady-state evaluation of the effects of propantheline bromide and cholestyramine on the bioavailability of digoxin when administered as tablets or capsules. AB - Drug interactions can profoundly alter the absorption of digoxin in tablet form. This study evaluated whether digoxin solution in capsules, a new dosage form with 90% to 100% bioavailability, would reduce such alterations, specifically those caused by cholestyramine and propantheline bromide. The investigation used a six treatment, steady-state, balanced, incomplete block design with 18 healthy adults studied for four continuous two-week treatment periods. Treatments were either two 0.25 mg digoxin tablets or two 0.20 mg digoxin capsules administered alone, with propantheline, 15 mg qid, or with cholestyramine, 8 g qd. Bioavailability was determined from steady-state, 24-hour area under the serum concentration-time curve (AUC, ng X h/mL) and from 0- and 24-hour trough serum digoxin concentrations (ng/mL). The AUCs for tablets alone, with cholestyramine, and with propantheline were 32.8 +/- 13.3 (+/- SD), 22.4 +/- 12.1, and 40.6 +/- 13.9, respectively, while corresponding values for capsules were 31.7 +/- 9.3, 24.7 +/- 7.9, and 35.9 +/- 12.8. The trough concentrations for tablets alone, with cholestyramine, and with propantheline were 0.88 +/- 0.47, 0.61 +/- 0.38, and 1.09 +/- 0.35, respectively; trough concentrations for capsules were 0.77 +/- 0.28, 0.74 +/- 0.28, and 0.96 +/- 0.48, respectively. The only significant differences in AUC were seen when comparing tablets alone versus tablets with cholestyramine (P less than .0005) and tablets with propantheline (P less than .01). A significant finding was also observed when comparing trough concentrations for tablets alone versus tablets with cholestyramine (P less than .005).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4031113 TI - Excretion of triamterene and its metabolite in triamterene stone patients. AB - As triamterene users may form kidney stones containing deposits of triamterene and its metabolites, we studied urinary excretion to detect any altered metabolism of triamterene in these patients. We found no significant differences between patients and matched control subjects in total recovery, hourly excretion patterns, and concentrations of triamterene and its sulfate metabolite. Approximately half of all subjects tested revealed urine concentrations of the sulfate metabolite that exceeded the observed solubility limit. PMID- 4031114 TI - Combined effect of bumetanide and metolazone in normal volunteers. AB - Bumetanide 1 to 2 mg or metolazone 2.5 mg were administered by mouth separately and then in combination to eight normal men and women in order to determine whether a sequential blockade of sodium reabsorption with diuretic agents that act at different sites within the nephron leads to a supra-additive diuretic effect. All three treatment regimens resulted in a significant weight loss and increased urine volume and the excretion of sodium, potassium, and chloride. A prolonged diuretic effect lasting up to 48 hours after administration occurred with metolazone alone. Although absolute and fractional chloride and potassium excretion and urine volume were higher after combined therapy (P less than .05 or better) than after either drug alone, absolute sodium excretion after combination therapy was higher than excretion after bumetanide (P less than .05) but not after metolazone. The percent of fractional sodium excretion after both drugs was greater than after either drug alone (P less than .05). However, excretion of chloride, sodium, potassium, and fluid on the combined therapy day was less than the sum of excretion on each single drug therapy day. Thus, the combination of bumetanide and metolazone did not have a supra-additive effect in normal subjects. PMID- 4031115 TI - Reliability of theophylline clearance in determining maintenance intravenous aminophylline therapy. PMID- 4031116 TI - The effect of rapid digitalization on ventricular function in patients with congestive heart failure. PMID- 4031117 TI - Lack of effects of diltiazem on digoxin pharmacokinetics. PMID- 4031118 TI - Pharmacokinetics of atenolol in patients treated with chronic hemodialysis or peritoneal dialysis. PMID- 4031119 TI - Spectral sensitivities of seven morphological types of photoreceptors in the retina of the turtle, Geoclemys reevesii. AB - Spectral sensitivities of photoreceptors in the turtle (Geoclemys) retina were studied by intracellular recording, and each cell was filled with Lucifer yellow (LY). Photoreceptors were classified into seven morphological types: rod, four types of single cones, and two members of a double cone. Single cones contained one of four different oil droplets: red, pale-green, orange, and clear. Double cones consisted of two apposed cones; principal members contained yellow oil droplets, while accessory members contained no oil droplet. Spectral sensitivities recorded from these seven types of photoreceptors were classified into one type of rod and three chromatic types of cones. Rods (n = 19) showed peak sensitivity at 520 nm. Single cones containing either a red (n = 51) or a pale-green (n = 9) oil droplet were red-sensitive (lambda max at 620 nm). Single cones containing an orange oil droplet (n = 14) were green-sensitive (lambda max at 540 nm). Single cones containing a clear oil droplet (n = 3) were blue sensitive (lambda max at 460 nm). Both members of the double cone, principal (n = 22) and accessory (n = 15), were red-sensitive (lambda max at 620 nm). No diffusion of LY was detected between the apposed members of double cones. Red sensitive cones, therefore, consisted of four different morphological types of cones, and they occupy about 70% of the photoreceptor mosaic in the turtle retina. PMID- 4031120 TI - Trigeminocerebellar, trigeminotectal, and trigeminothalamic projections: a double retrograde axonal tracing study in the mouse. AB - Double retrograde axonal tracing experiments were carried out in order to reveal potential patterns of divergence in axonal projections from the two major sensory nuclei of the mouse brainstem trigeminal complex: the principal sensory and spinal trigeminal nuclei (oralis, interpolaris, and caudalis divisions). The tracers wheat germ agglutinin, N-[acetyl-3H] and horseradish peroxidase were used in paired injection strategies within portions of the cerebellum, superior colliculus, and thalamic ventrobasal complex and/or posterior group of adult ICR white mice. Trigeminal neurons with projections to tactile areas of the cerebellar cortex or underlying deep cerebellar nuclei were found scattered throughout the principal sensory nucleus and interpolaris division, and mainly in dorsal regions of the oralis division of the spinal trigeminal nucleus. Injections of either tracer which involved lateral portions of the rostral half of the superior colliculus labeled trigeminotectal neurons mainly in the contralateral interpolaris division, ventral half of the oralis division, and a ventral region of the principal sensory nucleus near the oralis border. Fewer trigeminotectal neurons were found scattered throughout the principal sensory nucleus and the magnocellular layer of the caudalis divisions, although an occasional labeled neuron wa also found in the marginal layer. Contralaterally projecting trigeminothalamic neurons were observed throughout the principal sensory nucleus, interpolaris division, and within the marginal and magnocellular layers of caudalis. Double-labeled neurons were observed only after paired injections of the tracers in the thalamus and ipsilateral superior colliculus, and they were found within the caudoventral portion of the principal sensory nucleus near the oralis border, throughout the interpolaris division, within the magnocellular layer of caudalis, and only a few double-labeled neurons were also found within the marginal layer. After such injections, 50% of the labeled tectum projecting neurons in the principal sensory nucleus, 64% in the interpolaris division, and 57% in the caudalis division are branched neurons which have collateralized projections to both the superior colliculus and thalamus. These projections, which have not been described before, appear to arise from more than one class of projection neuron which is differentially distributed within different regions of the trigeminus. PMID- 4031121 TI - Patterns of muscarinic cholinergic binding in the striatum and their relation to dopamine islands and striosomes. AB - The distribution of muscarinic cholinergic binding sites in the striatum was studied in relation to the locations of other neurochemical markers in the developing rat, cat, ferret, and human. In addition, patterns of striatal muscarinic binding were studied in the adult cat. Receptor binding autoradiography was carried out with tritiated propylbenzilylcholine mustard [( 3H]-PrBCM), an irreversible muscarinic antagonist, and subsequent serial section analyses involved comparisons among patterns of muscarinic binding, catecholamine histofluorescence, acetylcholinesterase (AChE) staining, Nissl staining, and cell labeling with [3H]-thymidine. Muscarinic binding in the immature striatum was characterized by local patchiness as well as regional density gradients in all species, with the most complex patterns appearing in the human. Patches of dense muscarinic binding were shown to lie in register with fluorescent dopamine islands (rat, cat, ferret), with AChE-positive patches (all species), and with clusters of neurons pulse-labeled by exposure to [3H]-thymidine on embryonic day 27 (ferret). At the developmental stages examined, the [3H]-PrBCM-positive patches were roughly aligned with regions of weak Nissl staining (cat, human). Striatal [3H]-PrBCM binding in the adult cat was dense, and though it usually appeared nearly homogeneous, in some sections patches of elevated binding were present. These had as counterparts, in neighboring sections, AChE-poor striosomes. We conclude that during development muscarinic cholinergic function is compartmentalized in the striatum in association with dopamine-containing afferents, and that this compartmentalization may persist to some degree in the adult. PMID- 4031122 TI - Central projections of cat retinal ganglion cells. AB - The central projections of different groups of cat retinal ganglion cells were studied following small iontophoretic injections of horseradish peroxidase (HRP) into physiologically characterized sites. Analysis was restricted to labeled cells in the upper periphery of the nasal retina, contralateral to the injection site. Injections were made to the A lamina and C lamina of the dorsal lateral geniculate nucleus (LGNd-A,C), the geniculate wing (LGNd-W), the ventral lateral geniculate nucleus (LGNv), the pretectum (PT), and the superior colliculus (SC). The dendritic fields of alpha, beta, and epsilon cells were well labeled by the procedures we employed. A group, termed "g1," had somal sizes within the range of the smaller beta and epsilon cells, but dendritic morphologies distinct from either class. The g1 group may consist of a number of types, but our material provided no basis for further distinguishing them. Many cells were observed that had smaller somas; all had thin axons, and few had dendritic fields that labeled to any significant extent. We were not able to further distinguish these cells, and refer to this group, which may include a number of types, as "g2" cells. From the peripheral nasal retina, alpha cells project to LGNd-A, LGNd-C, PT, and SC. Beta cells project to LGNd-A, LGNd-C, and PT. Epsilon and g1 cells project to the LGNd-C, LGNd-W, LGNv, PT, and SC. We determined the total spatial density of cells in the region of the retina analyzed, using a Nissl-stained preparation. We then estimated the relative fraction of cells in each of the above groupings by injecting HRP throughout a cross section of the optic tract. Multiplying this relative fraction by the total spatial density gave an estimate of the spatial density of each of these groupings. From the spatial density of cells labeled from the injection site, we were able to estimate the fraction of cells of each retinal grouping that project to each of the zones investigated. By these calculations, almost all alpha cells from the upper nasal retina project to LGNd A and LGNd-C; most project to SC, and about a third to PT. Beta cells, by contrast, project almost exclusively to LGNd-A, with about 10% going to LGNd-C, and about 1% to the PT. The great majority of epsilon cells, if not all, project to LGNd-W, and up to half of this population also project to the other zones noted above.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 4031123 TI - Topography of the retinal projection to the superficial pretectal parvicellular nucleus of goldfish: a cobaltous-lysine study. AB - The retinal projection to the superficial pretectal parvicellular nucleus (SPp) of goldfish was examined by filling select groups of optic axons with cobaltous lysine. The tracer was applied intraocularly to peripheral retinal slits in some fish. In other fish, it was applied to optic axons from an intact hemiretina after one-half of the retina was ablated and the corresponding optic axons had degenerated. The results indicated that SPp is a folded structure, having a dorsal surface innervated by axons from temporal retinal ganglion cells and a ventral surface innervated by axons from nasal retinal ganglion cells. Peripheral retina innervates the anterodorsal and anteroventral edges of SPp, while central retina innervates the posterior genu. Dorsal retina innervates lateral SPp and ventral retina innervates medial SPp. Thus, although SPp is a folded nucleus, the topography of the retino-SPp projection is similar to the topography of the retinotectal projection. That is, the relative position of optic axons within SPp mirrors the retinal location of the ganglion cells that project to SPp. Retino SPp axons occupy the center of the main optic tract before it divides into the two optic brachia. These axons are topographically arranged, with temporal retino SPp axons being flanked on both sides by nasal retino-SPp axons. Retino-SPp axons arborize within SPp and then continue to enter the superficial tectal retino recipient lamina. Thus, these axons innervate both SPp and the optic tectum. These findings are discussed with respect to chemospecific and morphogenetic views of visual system topography. PMID- 4031124 TI - Projections to the basilar pontine nuclei from face sensory and motor regions of the cerebral cortex in the rat. AB - Orthograde axonal transport tracing methods were used to describe the projections to the basilar pontine nuclei (BPN) which arise within the face representation of motor or somatosensory cerebral cortex. Injections centered in motor face (MF) cortex resulted in the labeling of several corticopontine terminal fields which exhibit a rostrocaudal columnar arrangement within the ipsilateral BPN. The location of such terminal zones is consistent with the somatotopic pattern of termination previously described for limb sensorimotor cortices. In contrast, the projections from somatosensory face (SF) cortical regions largely terminate in BPN areas separate from those receiving either limb sensorimotor or MF inputs. Both MF and SF cortices also give rise to projections to the contralateral BPN; those from SF cortex are less extensive than those of MF origin. In addition to their relationship with limb sensorimotor corticopontine terminations, the MF projections to the BPN also seem to partially overlap the projection zones of the cerebellopontine system, particularly the regions projected upon by the lateral cerebellar nucleus. The SF projections, on the other hand, appear to terminate in BPN areas that also receive input from either the dorsal column nuclei or the spinal trigeminal complex. There is only minimal potential overlap between MF and SF projections in the BPN. With regard to the pontocerebellar system, the projections from MF cortex terminate among BPN neurons which project to the cerebellar hemispheres, particularly lobus simplex, crus I and crus II. The SF projections also overlap BPN neurons which project to the lateral hemispheres in addition to the paraflocculus and vermal lobules VII and IXa,b. Taken together these observations suggest that subsets of BPN neurons might exist such that some receive convergent inputs from systems whose function can generally be regarded as motor (sensorimotor cortex, cerebellopontine) while another population of BPN neurons might integrate signals from systems which transmit somatosensory information (dorsal column nuclei, spinal trigeminal). PMID- 4031125 TI - Ontogeny of tonotopic organization of brain stem auditory nuclei in the chicken: implications for development of the place principle. AB - The morphological development of the cochlea begins in the base or midbasal region and spreads toward the apex. In adults, the base responds maximally to high-frequency sounds and lower frequencies are represented progressively toward the apex. This predicts that responses to sound should occur initially to high frequencies and gradually change to include lower frequencies. Paradoxically, animals respond first to relatively low frequencies and last to high frequencies. We have previously proposed that this discrepancy results from an ontogenetic change in spatial coding of frequency along the cochlea (Rubel et al., '76). According to this model, only the basal end of the cochlea transduces sound early in development but it responds to low frequencies. During maturation the representation of low and midrange frequencies shifts apically and the base becomes responsive to high frequencies. This hypothesis predicts that the tonotopic organization within the central nervous system should change during development; neurons at any given location within an auditory nucleus should become maximally responsive to successively higher frequency sounds during development. In the present study this prediction was tested by using microelectrode recording procedures to map the tonotopic organization of nucleus magnocellullaris (NM) and nucleus laminaris (NL), first- and second-order auditory nuclei, in chickens at three ages: embryonic day 17, 1 day posthatch, and 2-4 weeks posthatch. The characteristic frequencies of neurons having the same anatomical location were quantitatively compared across ages. The tonotopic order in NM and NL was similar at all ages; responses to high-frequency sounds were recorded anteromedially and lower frequencies were located progressively more caudolaterally. However, there was a striking quantitative change in tonotopic organization. Neurons at a given location in both nuclei became maximally responsive to progressively higher frequencies during development. The characteristic frequencies of neurons in embryos and newly hatched chicks averaged, respectively, 1.00 (+/- 0.06, S.E.M.) and 0.34 (+/- 0.04) octaves lower than their predicted adult values. All regions in both nuclei showed a statistically significant increase in characteristic frequency during development except the most posterolateral (low-frequency) sector. Too few neurons were recorded from this region to be able to reliably estimate characteristic frequency. These results support the hypothesis that the spatial coding of frequency along the cochlea shifts during development.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 4031126 TI - The pathogenicity of some ovine or caprine mycoplasmas in the lactating mammary gland of sheep and goats. AB - Mycoplasma ovipneumoniae, M. arginini and M. conjunctivae were each inoculated into the lactating mammary gland of goats and sheep. M. ovipneumoniae was mastitogenic in both species, causing persistent colonization, raised lacteal cell numbers, decreased milk output and separation of milk into 3 layers throughout the periods of observation in virtually all animals. Its effects in sheep were variable, however, and appeared to depend less on the strain and titre of inoculum than on individual variation in response. M. arginini and M. conjunctivae were not mastitogenic for goats, but one of each pair of sheep injected with these agents showed organism persistence at high titres and lacteal neutrophilia over 9 days of observation. Effects on milk production were obscured by the apparent poor ability of the ovine udder to regain previous yield after a fall in output, but milk consistency and appearance were only temporarily or mildly affected in these animals. A. laidlawii, injected into sheep only, produced transient effects but with poor recovery of milk production after elimination of the organism. Goats were superior to sheep in consistency of reaction and milk output, and equally if not more susceptible to intra-mammary challenge with M. ovipneumoniae. The goat was therefore concluded to be the better experimental animal in a potentially useful method for screening strains of M. ovipneumoniae for virulence. PMID- 4031127 TI - Systemic arterial calcinosis in a grey tree kangaroo Dendrolagus inustus, resembling Monckeberg type arteriosclerosis in man. AB - A female grey kangaroo (Dendrolagus inustus) died from a severe systemic arterial calcinosis resembling arteriosclerosis of the Monckeberg type in man. Post-mortem findings, including scanning electron microscopy, are described and discussed with special reference to data in the literature. PMID- 4031128 TI - Border disease of sheep: spinal cord morphometry. AB - Semi-automated planimetry was used to determine cross-sectional areas of spinal grey and white matter by direct microscopy of paraffin sections of spinal cord from Border disease (BD) and normal lambs at segments C4, C8, T6 and L4. Spinal cord cross-sectional area was significantly reduced in cases of BD produced by either intramuscular or intranasal inoculation of ewes in the first half of pregnancy with Weybridge strains of BD virus. The reduction was apparent at all 4 levels and in both grey and white matter, though the white matter was the more severely affected. Spinal cord areas tended to be smaller in the progeny of ewes exposed earlier in gestation or to larger doses of virus, but these differences were not statistically significant. PMID- 4031129 TI - Electron microscopic observations concerning the in vivo uptake and release of the agent of guinea-pig inclusion conjunctivitis (Chlamydia psittaci) in guinea pig exocervix. AB - This report details electron-microscopical observations concerning C. psittaci infection in vivo. The model employed was that of the guinea-pig infected at the exocervical region with the agent of guinea-pig inclusion conjunctivitis (GPIC). Our observations indicate that chlamydial particles gain access to their target cells by the mechanism of endocytosis. Single GPIC elementary bodies were seen to be positioned within individual endosomes. The observations reported here provide evidence that chlamydial particles that had undergone their developmental cycle within the exocervical epithelial cells may leave the epithelium in 2 ways; within entire infected cells that had been shed into the lumen of the cervix and by means of the liberation of chlamydial particles from disrupted cells. The mechanism of cell disruption and shedding is thought to involve the large number of PMNs observed to be present within the enlarged intercellular spaces of the infected epithelium. PMID- 4031130 TI - Onchocerca raillieti: prevalence and pathology in Sudanese donkeys. AB - Onchocerca raillieti was found to be prevalent in Sudanese donkeys. The parasite was reported from Central, Northern, Western and Eastern Sudan and was most predominant in the last locality. The pathological changes produced by adult worms in the ligamentum nuchae are mostly chronic and do not seem to cause any clinical manifestations. Likewise, the microfilariae, though found in high densities in the skin with a "spill over" into the eyes, produce no pathological changes in either the skin or eyes. PMID- 4031131 TI - Dyschondroplasia/osteochondrosis of the femoral trochanter in the fowl. AB - Of 104 lame broilers, 12 birds with femoral trochanteric abnormalities were identified by post-mortem and radiographic examination. Defects occurred in ossification of either the trochanteric zenith or its medial aspect. Lesions were identified as dyschondroplasia, osteochondrosis or osteochondrosis dissecans affecting the articular surface of the femoral trochanter. In the absence of concomitant musculoskeletal disease, degrees of lameness can be attributed to trochanteric lesions. Breaches in the medial trochanteric bone plate permit granulation tissue repair of the articular surface. This repair process, however, did not compensate for the loss of articular surface contour and the junction of reparative and normal tissue may be prone to subsequent degeneration. PMID- 4031132 TI - Hip instability in young adult, broiler fowls. AB - In a study of spontaneous orthopaedic disease in 104 broiler-type birds fed ad lib, 14 cases of hip instability were detected. Female birds were commonly affected and all were aged between 20 and 30 weeks. Although hip luxation was not identified, in most cases the gait abnormality could be attributed to capital femoral ligament failure. There were two main patterns of capital femoral ligament disruption; either the ligament was avulsed, together with a cartilage fragment, from its foveal attachment, or the ligament itself was partially or totally ruptured. Histological evidence suggests that repetitive trauma or acute trauma of sufficient magnitude may be necessary for ligament disruption. It is likely that the excessive weight gain of ad-lib fed birds predisposes to ligament damage. PMID- 4031133 TI - Avulsion of muscles from the femoral trochanter in the fowl. AB - Post-mortem examination revealed lateral femoral trochanteric defects in 14 out of 104 broiler type chickens. All birds were severely lame, and in the absence of concomitant musculoskeletal disease trochanteric lesions were implicated in their clinical signs. Trochanteric muscle insertions had avulsed and the lateral metaphyseal defect was usually lined with granulation tissue. Examination of normal trochanteric development identified endochondral ossification at sites of muscle attachment. In some skeletally immature, proximal femurs evidence of osteochondrosis was detected at sites of trochanteric muscle attachment. It is deduced that broiler femoral trochanters are susceptible to muscle avulsion by virtue of their known predisposition to osteochondrosis and the pattern of muscle insertion. PMID- 4031134 TI - Congenital cystic disease of the liver in seven dogs. AB - Seven canine cases of cystic disease of the liver are described. They included 3 cases with solitary cysts, 3 with the adult type of polycystic disease of the liver and one with congenital dilatation of the bile ducts type V, i.e. fusiform dilatation of the intrahepatic and extrahepatic bile ducts. These findings are discussed with respect to the morphology and classification of human cases of cystic liver disease. PMID- 4031135 TI - Exposure of bovine cornea to different strains of Moraxella bovis and to other bacterial species in vitro. AB - A collection of strains of Moraxella bovis, some pathogenic and some non pathogenic in cattle, together with other M. bovis preparations, Neisseria ovis, Staphylococcus aureus and Moraxella non-liquefaciens were studied by scanning electron microscopy for their affinity to bovine corneal preparations in vitro. The in vitro procedure provides a convenient method for studies on host-pathogen interactions at the early stage of pathogenesis. The results corresponded well with the pathogenicity of the respective strains and species in cattle. It is considered that the pathogenicity of M. bovis is associated with at least two factors, piliation and the ability to produce pit-like depressions in corneal epithelial cells. The other bacterial species, which are not thought to play an important role in infectious bovine keratoconjunctivitis, had the ability to adhere to the bovine cornea but did not produce pits. The pitting factor of M. bovis is of interest in relation to studies on vaccination against infectious bovine keratoconjunctivitis. PMID- 4031136 TI - Syncytia formation: an aid in the diagnosis of canine distemper encephalomyelitis. AB - Syncytia formation has been observed in response to experimental Canine Distemper Virus (CDV) infection in specific-pathogen-free Beagle dogs. Multinucleated giant cells are most frequently found in white matter lesions of the brain and in the anterior uvea of the eye. Lymph nodes and the lung are occasionally positive, while the leptomeninges will also rarely harbour syncytia. The mechanism of syncytia formation and their possible importance in the pathogenesis of the disease are briefly discussed. Widespread tissue syncytia formation is a feature of CDV infection which should assist in identifying cases of non-suppurative encephalitis in the dog caused by this agent. PMID- 4031137 TI - Histological measurement of fat content of liver of dairy cows. AB - A total of 275 liver biopsies were performed on dairy cows in 6 Friesian and one Guernsey herd during the first 2 weeks after calving. Liver samples were processed by 2 independent histological procedures: (a) formalin-fixed frozen sections were stained with oil-red O (ORO), or (b) samples fixed in glutaraldehyde-osmium tetroxide were embedded in plastic and sections stained with toluidine blue (TOLB). The sections were then subjected to stereological point-counting procedures to assess the quantities of stainable fat present within the liver cells. Estimates of liver cell fat by the 2 techniques were highly correlated, although those obtained by the TOLB method were consistently lower than those obtained by the ORO method. The analytical sampling error was slightly lower in the TOLB method. The simpler ORO method should prove an acceptable alternative in the routine histology laboratory to the tedious and technically demanding TOLB method. PMID- 4031138 TI - Ultrastructural changes of the liver in spontaneously ketotic cows. AB - The ultrastructure of the liver in normal, mildly ketotic and severely ketotic cows was studied using stereological methods. In the liver of severely ketotic cows there is: (1) a significant increase in the volume fraction of hepatocytes and a decrease in the volume fraction of sinusoids, and (2) an increase in the volume fraction of lipid and smooth endoplasmic reticulum and a decrease in the volume fraction of glycogen and Golgi in parenchyma. A decrease in the profile density of mitochondria per 1 mm2 field and an increase of the volume occupied by mitochondria were not significant nor was the decrease in the volume density of rough endoplasmic reticulum. The degree and duration of negative energy balance obviously affect the morphological changes of the fatty liver. However, additional work is needed to determine the significance of ultrastructural changes in liver function. PMID- 4031139 TI - Calcium and phosphorus absorption in lambs exposed to Trichostrongylus colubriformis. AB - Ten lambs (29 +/- 1.2 kg) reared parasite-free and prepared with rumen, duodenal and ileal cannulae were paired and one of each pair was given a daily oral dose of 2500 Trichostrongylus colubriformis larvae for 14 weeks. Untreated animals received the amount of ration consumed by their infected pair-mates the previous day. During weeks 6 and 12 of infection, all lambs underwent a 7 day calcium (Ca) and phosphorus (P) balance. During weeks 7 and 13, duodenal and ileal samples were collected to determine the amounts of Ca and P entering and leaving the small intestine. The infection caused varying degrees of feed refusal in all infected animals. As a result, the data on Ca and P in excreta and the amounts of Ca and P entering and leaving the small intestine were regressed against dry matter (DM) intake for each group at each period. There were no between-period differences in these relationships. Calcium absorption and retention were unaffected by the stress of infection. Infection affected several aspects of P metabolism. Blood P concentrations were markedly reduced. Absorption of P from the small intestine was greater (P less than 0.01) in control lambs (at 1 kg DM intake 6.6 g per day) than in infected animals (2.2 g P per day), but there was a greater (P less than 0.05) duodenal flow rate of P in control lambs which suggested much higher rates of salivary secretion of P than in infected animals. Phosphorus flow rates at the ileum were greater (P less than 0.01) in infected lambs, despite the lower duodenal flow rates, which indicated a major abnormality (P less than 0.01) in small intestine absorption of P in infected animals; this may have contributed to the growth check experienced by these lambs. PMID- 4031140 TI - Nasal bacterial flora of clinically normal goats. AB - An enclosed swab assembly was employed to collect nasal mucus from 45 clinically normal goats. Eleven bacterial species were isolated from their nasal cavities. Pasteurella haemolytica and Pasteurella multocida were the most important isolates. PMID- 4031141 TI - Craniopharyngioma in a dog. AB - Craniopharyngiomas are rare in dogs. A 3 cm suprasellar craniopharyngioma in a 13 month-old male mongrel dog is described. The mass consisted of multiple microcysts and solid areas with mesenchymal proliferation in areas of transition. Tumour cells were arranged in solid sheets or separated into islands by thick bands of collagen. Squamous differentiation of tumour cells with keratin formation and a focus of osseous metaplasia were present. Occasionally, tumour cells were arranged in rosettes. Cysts were lined by a single layer of cuboidal to low columnar epithelium and contained proteinaceous fluid with numerous cholesterol clefts. The diagnosis was based on age of occurrence, location and histological appearance. PMID- 4031142 TI - Xanthomas and hyperlipidemias. AB - The ability to recognize diverse clinical forms of xanthomas, such as tuberous, planar, eruptive and tendinous, is important in the detection of underlying systemic disease. A variety of primary genetic disorders, as well as numerous secondary conditions such as diabetes, obstructive liver disease, thyroid disease, renal disease, and pancreatitis, can lead to hyperlipoproteinemia that results in the formation not only of xanthomas but also of life-threatening vascular atherosclerosis. An understanding of the pathogenesis of the underlying lipoprotein alterations provides a rational approach to therapy utilizing dietary manipulations and drugs. Such treatment is capable of correcting most disorders of lipid metabolism, and, if appropriate therapy is initiated at the first sign of xanthoma evolution, it may prevent progression of atherosclerosis, provide resolution of xanthomas, and in some instances prevent serious pancreatitis. PMID- 4031143 TI - Activation of herpes simplex following dermabrasion. Report of a patient successfully treated with intravenous acyclovir and brief review of the literature. AB - Herpes simplex labialis developed in a patient immediately following dermabrasion. The patient was hospitalized because the infection had spread rapidly over the dermabraded face and was complicated by secondary impetiginization. Herpesvirus hominis type I and Enterobacter aerogenes were isolated from cultures. Intravenous acyclovir and oral antibiotics were administered. On this regimen, new vesicle formation ceased in 36 hours. Complete resolution of the infection occurred within 6 days, with an excellent cosmetic result. Observation at 1 month confirmed no sequelae (in particular, scarring). The "at risk" patient with a history of recurrent herpes labialis should be identified prospectively in an attempt to prevent possible reactivation; should this complication ensue, appropriate treatment should be immediately administered because a state of local immunocompromise exists. We believe our patient benefited greatly from vigorous treatment, with significant shortening of time to healing. Prophylaxis with oral acyclovir of "at risk" patients prior to dermabrasion is proposed. PMID- 4031144 TI - Acute allergic contact dermatitis from diazolidinyl urea (Germall II) in a hair gel. AB - Diazolidinyl urea (Germall II) is a preservative recently used in cosmetics. It is effective against most contaminating microorganisms, especially Pseudomonas. We report the first case of an acute allergic contact dermatitis from diazolidinyl urea that was contained in a hair gel. PMID- 4031145 TI - Incontinentia pigmenti: a failure of immune tolerance? PMID- 4031147 TI - Lichen planus and chronic active hepatitis. PMID- 4031146 TI - Trazodone-induced hepatotoxicity and leukonychia. PMID- 4031148 TI - Crucial importance of the complete skin examination. PMID- 4031149 TI - Photochemotherapy (PUVA) and skin cancer. PMID- 4031150 TI - Idiopathic leukonychia totalis and partialis. PMID- 4031151 TI - Source of circulating testosterone and hirsutism. PMID- 4031152 TI - Response of the cutaneous lesions of Reiter's syndrome to ketoconazole. PMID- 4031153 TI - Familial lichen planus. More frequent than previously suggested? AB - In a follow-up study of 140 patients with lichen planus we found fifteen patients with a clinically and/or histologically verified family history of the disease, which gives a percentage much higher than that found in previous studies. The reason for this discrepancy might be caused by difficulties in the detection of the disease in family members. Familial lichen planus was found to be different from nonfamilial lichen planus, especially in its effect on young persons and in being a more widespread type with a tendency to result in relapse. The high incidence of familial lichen planus supports the hypothesis that genetic factors are of etiologic importance in lichen planus. PMID- 4031154 TI - Sclerodermoid changes of porphyria cutanea tarda: possible relationship to urinary uroporphyrin levels. AB - From 1950 to 1982, fifteen patients were seen at the Mayo Clinic with a diagnosis of sclerodermoid changes of porphyria cutanea tarda. Fourteen patients had changes similar to scleroderma limited to the skin, and one patient had scleroderma-like skin changes accompanied by visceral abnormalities. Both light exposed and unexposed areas of the body were affected. Areas of involvement included the chest, the V-shaped area of the neck, and the back, face, and shoulders. In six patients, morpheaform changes represented the presenting cutaneous sign of porphyria cutanea tarda. Follow-up examination, after treatment that included abstinence from alcohol and phlebotomy, revealed that the sclerodermoid skin changes had disappeared in six patients and improved in four. Generally, the degree of improvement of the sclerodermoid changes was proportional to the reduction of the urinary uroporphyrin levels toward normal (p = 0.02). PMID- 4031155 TI - Complex aphthosis: a forme fruste of Behcet's syndrome? AB - The evaluation of the rare patient who presents with oral and genital aphthae or almost constant, multiple (greater than 3) oral aphthae, but no systemic signs or symptoms (i.e., complex aphthosis), is difficult because no laboratory test is available to exclude Behcet's syndrome. Six patients with complex aphthosis were evaluated. In addition, patients with simple aphthosis, those with seronegative arthritis, and normal controls were assessed for circulating immune complexes (CIC) by in vitro and in vivo assays and for neutrophil migration by subagarose methods, since these tests have given significant results in patients with Behcet's syndrome. Patient 1, with complex aphthosis, had Raji cell evidence for CIC (51.2 mg aggregated human gamma globulin Eq/ml), C1q, and C3 in dermal blood vessels 4 hours post intradermal histamine injection and had a Sweet's syndrome like vasculitis 24 hours post histamine injection. In addition, her serum enhanced the migration of patient neutrophils (3.6 +/- 0.6 to 4.6 +/- 0.5; N = 6, p less than or equal to 0.01). All other test and control patients had negative or normal CIC and neutrophil migration determinations. Sixteen-month clinical follow-up has confirmed that Patient 1, but not Patients 2 to 6, has developed overt manifestations of Behcet's syndrome. PMID- 4031156 TI - Uncombable hair syndrome: observations on response to biotin and occurrence in siblings with ectodermal dysplasia. AB - Three children are reported with uncombable hair syndrome, consisting of slow growing, straw-colored scalp hair that could not be combed flat. The hairs appeared normal on light microscopy but on scanning electron microscopy were triangular in cross section, with canal-like longitudinal depressions. Oral biotin, 0.3 mg three times a day, produced significant improvement after 4 months in one patient, with increased growth rate and with strength and combability of the hair, although the triangular shape remained. The other two patients were unique in having associated ectodermal dysplasia. Their hair slowly improved in appearance and combability over 5 years without biotin therapy. PMID- 4031157 TI - Netherton's syndrome. Report of a case and review of the literature. AB - A patient with Netherton's syndrome who was followed since birth had previously been diagnosed as having Leiner's disease and acrodermatitis enteropathica; the disorder was recognized clinically when the patient was 20 years of age. Therapy with 13-cis-retinoic acid significantly aggravated the ichthyosis and induced increased fragility of the skin. This patient also had an intermittent aminoaciduria with clinical investigations that showed normal renal function. Furthermore, the aminoaciduria resolved spontaneously after the discontinuance of topically applied corticosteroids. The normal results of clinical studies and a review of the literature suggest that the aminoaciduria may have been artifactual because excess absorption of topically applied corticosteroids directly affects the renal tubules and impairs renal reabsorption or enhances the free excretion of amino acids. We review forty-two other cases of Netherton's syndrome in the literature and reaffirm the significance of associated ichthyosis, atopy, trichorrhexis invaginata, and other findings in this unique syndrome. PMID- 4031158 TI - Chediak-Higashi syndrome in a Venezuelan black child. AB - One case of Chediak-Higashi syndrome (CHS) in a black male child, born to a consanguineous couple from a rural village in the State of Falcon, is described. At birth the child had marked skin depigmentation and ash-gray hair. A few months later he developed an almost normal black skin color. The diagnosis of CHS was established by the presence of large peroxidase-positive granules in his leukocytes. Neutrophils showed decreased chemotaxis and lack of digestive capacity against Candida albicans. Unusual features included extreme rarity of CHS in blacks, progressive repigmentation of the skin, and an early benign evolution. A high consanguinity index in the village from which this patient originated raised the possibility of the presence of a new cluster of this disease in Venezuela. PMID- 4031159 TI - Balloon cell malignant melanoma. AB - A patient was seen with a pigmented plaque of malignant melanoma and multiple surrounding skin-colored dermal and subcutaneous nodules. Histologic examination showed that the pigmented lesion represented the balloon cell variant of malignant melanoma and that the adjacent nodules were local metastatic lesions. This case, along with a review of the literature, illustrates that many balloon cell melanomas show only mild cellular atypia and minimal mitotic figures, although the tumor has a malignant course, with local or distant metastasis. A careful examination of all the sections of the balloon cell tumor is important. PMID- 4031160 TI - Basal cell tumor with apocrine differentiation: apocrine epithelioma. AB - A locally invasive tumor developed in a 71-year-old woman on the right retroauricular skin, involving cartilage and parotid glands. Histologically, the tumor displayed characteristic features of basal cell epithelioma accompanied by stromal fibrosis. Histochemically, an apocrine pattern in enzyme reactions was detected in tumor cells. Ultrastructurally, the tumor cells showed the features of apocrine-type secretory cells and ductlike structures, and the peripheral cells revealed the characteristics of myoepithelial cells. A large number of myofibroblasts was observed in the connective tissue surrounding the tumor nests. From these findings, the woman's tumor was considered to represent a basal cell tumor with apocrine differentiation. PMID- 4031161 TI - Polymyositis presenting with panniculitis. AB - Although microscopic areas of panniculitis may frequently occur in patients with dermatomyositis and polymyositis, large, clinically obvious plaques are unusual. We report a patient with polymyositis who initially had panniculitis of the thigh. Histologically, a lobular lymphoplasmacytic infiltrate was present in the subcutis. PMID- 4031162 TI - Cutaneous horns of the penis: an approach to management. Case report and review of the literature. AB - Cutaneous horns of the penis are rare lesions, only seventeen previous cases having been reported in the English literature. The lesions usually appear following adult circumcision for long-standing phimosis. Frequently they are unusual presentations for squamous cell carcinoma of the penis. One third of the cases of penile horns were associated with underlying malignancies; therefore prompt surgical intervention is warranted. PMID- 4031164 TI - Computed tomography of spondylolisthesis: patterns of associated pathology. AB - Spondylolisthesis was observed in 165 of 2,500 patients with back pain evaluated by CT. In more than two-thirds of these patients a second structural abnormality was found in association with the spondylolisthesis. The nature and location of this second abnormality varied with the type of spondylolisthesis: spondylolytic or degenerative. Spondylolytic spondylolisthesis, caused by a defect in the pars interarticularis, was associated with foraminal stenosis at the level of the defect in the pars and disk protrusion at the interspace immediately above this level. Degenerative spondylolisthesis, caused by facet joint disease, was associated with disk protrusion and spinal stenosis at the same level as the spondylolisthesis. The advantages and limitations of CT in the evaluation of symptomatic patients with spondylolisthesis are discussed. PMID- 4031163 TI - Effects of dexamethasone treatment on acoustic neuromas: evaluation by computed tomography. AB - Five patients with unilateral acoustic neuromas were studied with CT before and after treatment with dexamethasone. Rather small effects, in the order of 10-20%, were observed on the parameters evaluated, including the size of the tumor, size of the peritumoral edema, and the contrast enhancement. Hence, the acoustic neuromas, which ultrastructurally and with their extraaxial location bear great resemblances to meningiomas, also show a similarity in their minimal response to steroid treatment. PMID- 4031165 TI - Menstrual variation of normal breast NMR relaxation parameters. AB - Nuclear magnetic resonance (NMR) offers great promise in noninvasively distinguishing normal, benign, and malignant tissues in the breast. However, well documented changes that occur in breast tissues during the normal menstrual cycle suggest that lesion detectability will depend on knowledge of the variations in NMR parameters that occur as a consequence of these changes. Correct selection of optimal NMR pulse sequences and interpulse times, based on spin density and T1 and T2 values, to maximize tissue contrast and lesion detectability, will likewise depend on our understanding of variations in NMR parameters of normal breast tissues. The purpose of this study is to determine the range and variability of NMR parameters (spin density, T1 and T2) associated with changes in normal breast tissues during the menstrual cycle, as measured by NMR imaging. Initial findings suggest that there are measurable differences between breast tissues as a function of time in the menstrual cycle. PMID- 4031166 TI - Distinction between adrenal adenomas and metastases using MR imaging. AB - Magnetic resonance imaging was performed on 12 patients with known neoplastic disease and adrenal masses shown by CT. Three patients with metastases had high signal intensity in the adrenals on T2 weighted spin echo scans (SE 2,500/80) and nine patients with nonfunctioning adenomas had low signal intensity on T2 weighted images. The ability to distinguish metastases from nonhyperfunctioning adrenal adenomas may be of use in the pre-operative evaluation in patients with known carcinoma and incidental adrenal masses. PMID- 4031167 TI - MR imaging of uterine leiomyomas and their complications. AB - Magnetic resonance (MR) imaging in eight patients with uterine leiomyomas and in eight normal female volunteers clearly depicted the size, shape, and position of the corpus uteri and demonstrated adjacent anatomic structures to good advantage in transaxial, coronal, and sagittal planes. Spin echo (SE) with short repetition time (TR) and short echo time (TE) values was judged best for overall delineation of anatomic structures. Longer TR and TE times were used to differentiate myometrium from endometrium. Detection and characterization of complications of uterine myomas were facilitated by the use of multislice/multiecho SE techniques, but in general TE values greater than 60 ms were not needed to differentiate endometrium from myometrium and in most cases did not improve the MR depiction of abnormalities. Calculated T1 and T2 relaxation times from this preliminary study do not demonstrate a clear advantage in further characterizing uterine abnormalities. PMID- 4031168 TI - MR imaging of intramuscular hemorrhage. AB - This retrospective study was performed to (a) analyze the appearance of normal striated muscle using the spin echo (SE) technique and (b) evaluate the potential of magnetic resonance (MR) imaging for demonstrating intramuscular bleeding. Magnetic resonance examinations of 30 patients imaged for reasons other than muscular disorders were reviewed. Normal striated muscle was always imaged with a lower intensity than fat because muscle had a longer T1 and a shorter T2 than fat. Furthermore, the spin density of muscle was less than that of fat. The best contrast between the two tissues was obtained with a short repetition time (TR) of 0.5 s and a long echo time (TE) of 56 ms. In addition, five MR examinations from three patients with intramuscular bleeding were assessed. In one case the CT examination was also available for comparison. In every case MR permitted the diagnosis and demonstrated the precise extent of intramuscular bleeding and its regression after therapy. The MR diagnosis of intramuscular bleeding was readily performed because of the excellent contrast resolution of the technique. These lesions were always brighter than the surrounding normal muscle. The optimum SE technique, which enhanced contrast between the muscle and the site of bleeding, was a long TR of 2.0 s and a long TE of 56 ms. The T1 and T2 relaxation times of intramuscular bleeding were always longer than those of normal striated muscle. Preliminary results indicate that MR is very sensitive for the demonstration of intramuscular bleeding. PMID- 4031169 TI - Hemiatrophy of the tongue and floor of the mouth demonstrated by computed tomography. AB - Computed tomography can show hemiatrophy of the tongue and the floor of the mouth. The normal neuroanatomy of this region with regard to its motor supply is reviewed. In theory six variants of motor nerve lesions with hemiatrophy can be encountered, three of which are illustrated in this report. Knowledge of the muscular anatomy and the motor nerve supply to the tongue and floor of the mouth is helpful when evaluating lesions of the base of the skull with CT. This is particularly true for the lesions involving the trigeminal and hypoglossal nerves. PMID- 4031170 TI - MR imaging of the normal larynx. AB - Magnetic resonance imaging of the larynx was performed on 15 volunteers. Searching for optimal images in the sagittal, frontal, and transverse planes, we compared images made with a special surface coil and the standard head coil, images with different slice thicknesses, images with different repetition times (TR) and images with different matrices. The field of view and the scan times were kept as small as possible. Using a surface coil, we obtained high resolution images in all three planes. These images provide clinically relevant information, not shown by current radiological techniques: hyoepiglottic ligament, thyrohyoid ligament, thyroepiglottic ligament and cricothyroid ligament, the borders between the preepiglottic space and both paraglottic spaces (PGS), the borders between both PGS and thyroid cartilage, and the vocalis and thyroarytenoid muscles. Short TR is preferred because, with shorter scan time, more measurements could be made. Images with a 128 X 128 matrix size had a much better signal-to-noise ratio than images with a 256 X 256 matrix size. Magnetic resonance has great potential in imaging normal and pathological anatomy of the larynx. PMID- 4031171 TI - Scatter radiation from abdominal CT examinations. AB - Several water phantoms were scanned under a number of conditions and radiation exposure due to scatter was measured at the center of one end. The decrease of the scatter radiation exposure is nearly exponential with distance from the slice plane. The half-value distance is a function of the slice cross-sectional area. An empirical equation is presented to relate exposure to the pertinent variables. PMID- 4031172 TI - CT demonstration of tethering of the lung by the pulmonary ligament. AB - An unusual form of atelectasis has been detected on CT of a patient with large pleural effusions. It has been interpreted to be the result of tethering of the lungs to the mediastinum by the pulmonary ligaments, which may have lacked normal elasticity in this case because of prior irradiation. This appearance may simulate a collection of dense material on the surface of an effusion when there is no obvious air bronchogram present. PMID- 4031173 TI - Preoperative evaluation of bronchiectasis by computed tomography. AB - A patient with known lingular bronchiectasis is presented for whom CT was used as the sole preoperative radiographic method to exclude disease in the remainder of the bronchial tree. The patient has remained symptom free for 12 months following lingulectomy. The potential of CT to obviate the need for bronchography in the preoperative staging of bronchiectasis is discussed. PMID- 4031174 TI - Bronchogenic cyst causing superior vena cava obstruction: CT appearance. AB - The CT appearance of bronchogenic cysts is well known. In addition, CT is useful in evaluating cases of suspected superior vena cava (SVC) syndrome. Although most cases of SVC syndrome are caused by malignant diseases, certain benign disorders such as granulomatous infections may be the underlying cause. A case of a bronchogenic cyst causing SVC occlusion is presented here. PMID- 4031175 TI - CT diagnosis of closed loop obstruction. AB - A case of closed loop obstruction presenting with unremarkable plain abdominal films and diagnosed by CT is reported. The presence of (a) fluid filled distended small bowel loops; (b) abrupt transition with collapsed distal intestinal loops; and (c) grossly distended fluid filled "U" shaped loop are diagnostic of this entity. Prompt CT recognition, before signs of intestinal gangrene develop, will lead to immediate surgical decompression and a significant decrease in the morbidity and mortality of this potential abdominal catastrophe. PMID- 4031176 TI - CT diagnosis of fluid in lesser sac mimicking thrombosis of inferior vena cava. AB - A patient with ascites and fluid in the lesser sac mimicking the appearance of a clot in the inferior vena cava is described. A knowledge of liver anatomy, particularly the lesser sac in the region of porta hepatis, aids in avoiding this CT pitfall. PMID- 4031178 TI - CT findings of metastatic breast carcinoma involving muscle. AB - Hematogenous metastatic disease to skeletal muscle is a very unusual occurrence and is seldom diagnosed clinically. This case report demonstrates the CT findings of metastatic breast cancer to skeletal muscle of the neck. PMID- 4031177 TI - Adrenal myelolipoma associated with Conn syndrome: CT evaluation. AB - A case of myelolipoma and Conn syndrome due to an ipsilateral aldosteronoma is documented, and CT findings are presented. PMID- 4031179 TI - MR imaging of iliopsoas bursitis and concurrent avascular necrosis of the femoral head. AB - The magnetic resonance (MR) features of iliopsoas bursitis secondary to an inflammatory arthropathy of the hip are described in a patient with concurrent avascular necrosis of the femoral heads. The MR findings of avascular necrosis were demonstrated on one side where radiography, bone scan, and CT were negative. PMID- 4031180 TI - High-field MR imaging of superficial siderosis of the central nervous system. AB - A case of superficial siderosis of the central nervous system secondary to bleeding from an ependymoma is presented. High-field magnetic resonance imaging showed marginal hypointensity of the cervical cord, medulla oblongata, pons, mesencephalon, anterior cerebellar and basal cerebral surfaces, and cranial nerves (II, V, VIII). These findings were evident in the T2 weighted images. PMID- 4031181 TI - Actinomycotic brain abscess: CT findings. AB - An unusual case of actinomycotic brain abscess with histologic documentation is reported. Commonly, a primary focus of actinomycosis in the cervicofacial, thoracic, or abdominal areas is found. In our particular case such a primary source of infection was not evident. Cranial CT showed a thick-walled ring enhancing lesion deeply located in the left parietal region. This CT finding was useful but not diagnostically pathognomonic. Correct diagnosis was made based on histologic findings. Sulfur granules and Gram-positive branching organisms were seen in the purulent material. PMID- 4031182 TI - Postmyelographic CT evaluation of multiple blocks due to metastases. AB - A case of intraspinal metastatic carcinoma that presented on combined cervical and lumbar puncture metrizamide myelography as complete blocks at T2 and T12 is described. The extent of disease in the long segment of the spinal canal was inaccessible to conventional myelography. This case illustrates the importance of postmyelogram CT for accurate assessment of disease and for treatment planning. PMID- 4031183 TI - Traumatic perforation of the pyriform sinus: CT demonstration. AB - Hypopharyngeal perforation secondary to tracheal intubation is a rare and serious complication. Radiographic evaluation is helpful when the clinical diagnosis is not obvious. In one such case CT demonstrated the site of perforation and its extension into the superior mediastinum, facilitating the subsequent surgical approach. PMID- 4031184 TI - Vertebral hemangioma with compression myelopathy: metrizamide CT demonstration. PMID- 4031185 TI - Movement and absorption of major minerals and water in ovine gastrointestinal tract. AB - Movement of calcium, chloride, magnesium, potassium, sodium, and water in the intestine of sheep was determined with cerium-141 as an unabsorbed reference substance. Net secretion of phosphorus and sodium, but not of potassium and calcium, was observed to the rumen. Water disappeared from the omasum and was secreted in the abomasum. Chloride secretion occurred in the omasum and more in the abomasum. Extensive secretion in the duodenum increased flows of sodium and potassium 8 to 9 times; of calcium, chloride, and phosphorus 3 to 6 times; of magnesium 1.3 times; and of water 12 times. Reabsorption was rapid in the small intestine, the major site of disappearance of all ions. Rates of disappearance decreased with increasing distance from the pylorus. Little further net disappearance of calcium, phosphorus, magnesium, or potassium was found in the large intestine, whereas water, sodium, and chloride disappearance continued. Overall absorption of sodium, potassium, and chloride was approximately 90%, of phosphorus 63%, of calcium 38%, and of magnesium 71%. This study highlights the importance of endogenous secretions in mineral absorption in the sheep. PMID- 4031186 TI - Digestion and absorption of lipids and bile acids in sheep fed stearic acid, oleic acid, or tristearin. AB - Sheep were fed diets containing 7.5% added stearic acid, oleic acid, or tristearin for 21 days. In addition, 50 microCi/kg cerium-141 was included for the last 10 days on experimental diets as an unabsorbed reference substance. In the rumen dietary triglycerides were approximately 50% hydrolyzed, and hydrogenation resulted in saturation of the free fatty acid fraction. Some net synthesis of phospholipids, presumably microbial phospholipids, occurred in the rumen. In the intestine immediately distal to the pylorus, extensive secretion of bile acids, cholesterol, phospholipids, triglycerides, free fatty acids, and lipase occurred. This resulted in doubling of fatty acid fluxes through the duodenum. These endogenous secretions were reabsorbed rapidly however, with the major site of lipid and bile acid absorption in the region .6 to 4 m distal to the pylorus. Additional but less absorption occurred in the more distal segments of the small intestine. Overall absorption of stearic acid, oleic acid, and tristearin supplements was in the range 60 to 70%, and no differences were apparent between fats. Unsaturated fatty acids were over 90% absorbed as compared with 55 to 65% for saturated fatty acids. No significant effect of any of the supplements was observed on ruminal total volatile fatty acids, ratios of volatile fatty acids, or on overall cellulose or caloric digestion. PMID- 4031187 TI - Digestion and absorption of protein along ovine gastrointestinal tract. AB - Digestion and absorption of protein were determined in ovine gastrointestinal tract with cerium-141 as an unabsorbed reference substance. Nitrogen flows changed little in rumen and reticulum, but in the proximal small intestine flows increased because of secretion of .9 g nitrogen per day per kg body weight. This secretion included trypsin, chymotrypsin, elastase, and carboxypeptidases A and B; maximal activity was in proximal segments of the small intestine and decreased with distance from the pylorus. Activity of chymotrypsin decreased more rapidly than that of trypsin. Amino acid flows reflected the influx of protein in the duodenum; absorption was approximately 55% in the terminal ileum. No major changes of proportions of individual amino acids were observed. Overall nitrogen absorption was 72.6% of which 6% was in the large intestine. The major soluble protein fraction in the gastrointestinal tract consisted of peptides with molecular weight 7,000 to 14,000 daltons. Soluble high molecular weight protein was observed only in rumen and duodenum. Low molecular weight peptides and amino acids accumulated only in the proximal small intestine. Solubilization of protein and breakdown of peptides of 7,000 to 14,000 molecular weight appear to be rate limiting for protein absorption in sheep. PMID- 4031188 TI - Effects of adding beta-carotene to rations of lactating cows consuming different forages. AB - Thirty-six Holstein cows fed a corn silage-based ration and 34 fed an alfalfa grass silage-based ration were assigned according to calving date to receive either 300 mg/head per day of synthetic beta-carotene in a gelatin capsule or an empty gelatin capsule daily for the first 100 days postpartum. Supplemental vitamin A was provided at 3919 IU/kg of ration dry matter. Cervix diameters for cows supplemented with beta-carotene were smaller at 21 days and 28 days postpartum. Days from parturition to first observed estrus were less when beta carotene was added and less when corn silage was fed. Means of other reproductive traits were more favorable for cows treated with beta-carotene (fewer services per conception and shorter intervals between parturition and conception). Milk progesterone at 21 and 28 days postpartum was not affected by either roughage or beta-carotene treatment. Milk from cows receiving alfalfa-grass silage contained lower somatic cell concentrations than that produced by cows fed corn silage. Milk somatic cell concentrations were lower in both roughage treatment groups for cows supplemented with beta-carotene. No effects of roughage or beta-carotene on milk production or milk fat percentages were significant. PMID- 4031189 TI - Evaluation of potato meal as a feedstuff for lactating dairy cows. AB - Potato meal was ensiled with a grass-legume forage at 7.5% of fresh weight and substituted for ground corn in concentrate mixtures at 0, 15, and 30% fresh weight. Production, digestion, and nitrogen balance trials were conducted on 12 lactating Holstein cows fed individually for ad libitum intake. Potato meal was consumed readily in the quantities offered. Mean daily milk production for cows receiving the hay-crop silage ensiled with potato meal was 28.6 compared with 26.3 kg for cows consuming untreated silage. Molar percentages of acetate in rumen were lower and propionate higher for cows receiving hay-crop silage ensiled with potato meal. Digestibility coefficients for dry matter, organic matter, acid detergent fiber, neutral detergent fiber, crude protein, and gross energy all tended to be lower for the silage with added potato meal. Nitrogen balance was higher for cows consuming silage with potato meal. When potato meal was added to concentrate mixes replacing corn at 0, 15, and 30%, milk production was 27.5, 26.8, and 28.0 kg/day. Potato meal can be used advantageously as a silage additive and can be included in concentrate mixtures up to 30% of the fresh weight. PMID- 4031190 TI - Effect of dry matter intake from whole goat milk and calf milk replacer on performance of Nubian goat kids. AB - The dry matter in calf milk replacer was compared with dry matter in goat milk for Nubian goat kids. Kids were fed the following diets from 4 days of age for 6 wk: 1) whole goat milk (14.0% dry matter), 2) calf milk replacer (13.5% dry matter), and 3) calf milk replacer (18.0% dry matter). Body weight of kids fed whole milk and 18.0% dry matter milk replacer increased each week. Kids fed the 13.5% dry matter milk replacer increased in weight to the 3rd wk but steadily declined thereafter. Total weight gain was more for kids fed whole milk (3.89 kg) than for kids fed milk replacer diets with 13.5 or 18.0% dry matter (.79 and 3.06 kg, respectively). For the first 3 wk, average daily gain was lowest for kids fed 18.0% milk replacer diet, but highest for wk 4 to 6. These data indicate that 3 week-old goat kids can utilize large amounts of dry matter from milk replacer to sustain a rate of growth similar to that of kids fed whole milk; however, high amounts of dry matter from milk replacer are poorly utilized by kids during the first 3 wk of life. PMID- 4031191 TI - Components of variance and covariance between direct and fetal effects in production traits. AB - The correlation between sire of fetus effect and sire of cow effect on three production traits - milk yield, fat yield, and protein yield - in first lactation cows was investigated. Restricted maximum likelihood techniques were used. There was a small sire of fetus variance for milk yield, h2 .23%, while the sire of fetus variances for fat and protein were very small and negative. For milk yield the genetic correlation between sire of fetus effect and sire of cow effect was .82. The negative sire of fetus variances for fat and protein precluded calculation of genetic correlations, both with sire of cow effects for fat and protein, and with each other and with milk yield for sire of fetus effects. PMID- 4031192 TI - Estimation of genetic parameters for stayability in Canadian Holsteins. AB - Hazard functions were plotted and troughs were used to define stayability traits that best coincided with the time of culling decisions. Traits evaluated were stayability to 17, 30, 43, and 55 mo of productive life and stayability to 42, 54, 66, and 78 mo of total life. Holstein data from Record of Performance and supervised Dairy Herd Improvement and Dairy Herd Analysis Service testing programs formed two data sets with 243,348 and 118,362 daughters of 10,723 and 4,583 sires, respectively, and were used to estimate stayability heritabilities and correlations. Variance components were estimated by Henderson's new method using a model that included a fixed herd-year-season of first calving effect and random sire and error effects. Heritabilities for stayability to 17, 30, 43, and 55 mo of productive life were .025, .040, .039, and .033, respectively, for the Record of Performance data and .010, .017, .023, and .033, respectively, for the Dairy Herd Improvement-Dairy Herd Analysis Service supervised data. Heritability estimates for stayability to 42, 54, 66, and 78 mo of total life were .051, .040, .045, and .059, respectively, for the Dairy Herd Improvement-Dairy Herd Analysis Service supervised data. Genetic correlations among productive life traits were usually very high and approached unity. Genetic correlations among total life traits were lower and more variable. Most phenotypic correlations were moderately high but some were low. Stayability to 17 mo of productive life was concluded to be the best trait for incorporation into a selection program if evaluation of sires for longevity is desired. PMID- 4031193 TI - Relationships between herd type and genetic and environmental variances in Holsteins. AB - Type classification data from the Holstein Association of Canada on 354,308 daughters of 13,694 sires were subdivided into 20 groups of approximately equal size according to herd average final score. Genetic and environmental variances were estimated for each group by Henderson's new method. Traits considered and their heritabilities averaged over groups were: final score .13; final class .11; dairy character .17; capacity .24; rump .16; feet and legs .10; mammary system .12; fore udder .12; rear udder .12; size .31. Regressions of genetic variances on group number ordered according to herd final score indicated significant trends only for rump and feet and legs for which higher genetic variances were found for higher type scores. Regressions of environmental variances on group number were significant for all traits. Higher environmental variances were found for lower final scores, final class, dairy character, and capacity, but the opposite was observed for size. The distribution of environmental variances across groups was U-shaped for rump, feet and legs, for udder, and rear udder; lowest variances were associated with intermediate scores for overall type. PMID- 4031194 TI - Differences in modified contemporary comparison sire evaluations from first and later lactations by breed. AB - Sire evaluations from three sets of daughter records, first records only (first), later records after firsts (later), and all records (all) by Modified Contemporary Comparison procedures were used to examine differences in first and later lactation evaluations by breed. January 1984 evaluations for milk for 767 Ayrshires, 3,175 Guernsey, 29,498 Holstein, 3,530 Jersey, and 984 Brown Swiss bulls with 10 or more daughters in each set were used. Average differences between evaluations (later minus first) were 36, 0, 6, 35, and 35 kg milk for Ayrshire, Guernsey, Holstein, Jersey, and Brown Swiss bulls. Standard deviations of the difference were 114, 94, 142, 91, and 134 kg, showing considerable sire-to sire variation in difference. Correlations between evaluations based on first and later records were .84 to .86 for all breeds except .92 for Jerseys. Percent of first lactations culled was correlated .20, .18, .16, .16, and .19 with difference for Ayrshire, Guernsey, Holstein, Jersey, and Brown Swiss, indicating that culling produced larger differences between evaluations for first and later lactations in favor of later evaluations. Prediction of sire evaluation from later records was enhanced by knowledge of sire's age in addition to first evaluation for Guernsey, Holstein and Jersey sires. In these breeds, for a constant first evaluation, and percent culled in first lactation, younger bulls had higher evaluations from later records. This study showed important differences between evaluations from first and later records for all breeds. PMID- 4031195 TI - Factors affecting reproductive performance of dairy cows. AB - We conducted two studies to determine how herd management practices and traits of individual cows affect performance of the herd and of the cow within a herd. Management practices, reproductive performance of the herd, and relationships between management and reproductive performance were characterized on 83 dairy farms with 7596 cows. Data included 21 management variables (e.g., facilities, herd health program, estrous detection program) and 8 performance variables obtained from Dairy Herd Improvement or unofficial records (e.g., size of herd, production, days open). Although varying among herds, annual average herd incidences of reproductive disorders and reproductive performance were similar to those reported. Managerial practices influenced incidences of retained placenta and uterine infection, days open of cows not bred and of all cows, services per conception, and percentages of herd open more than 100 days and culled for low production. Veterinarian was the most consistent variable influencing herd reproductive performance. Data also were collected from production and lifetime records of 2532 cows in 19 herds. Reproductive performance was affected by season of calving, production, maturity, and reproductive disorders. Several cows with extremely poor reproductive records were maintained. PMID- 4031196 TI - Interrelationships of milk yield, body weight, and reproductive performance. AB - Records (2263) from a single north Florida herd for 3 yr were evaluated in a series of analyses. Environment was subtropical. Data set included only cows that had normal milk records and became pregnant. Holsteins and Jerseys averaged 6799 and 4504 kg milk, 587 and 418 kg postpartum body weight, 164 and 141 days open, and 2.3 and 2.1 services per subsequent pregnancy. Pooled within breed, repeatabilities and heritabilities of these performance measures were .37, .15; .53, .25; .20, .06; and .30, 0. Estimable genetic correlations were milk yield and body weight -.09, milk yield and services per conception .38, and services per conception and body weight .37; range of standard errors was .22 to .39. Substantial genetic antagonism may exist between milk yield and body weight, and efficient reproduction. If results of this research are verified elsewhere, breeders should be aware that selection for increased weight could lead to decreased reproductive efficiency. PMID- 4031197 TI - Comparison of total and free cortisol in bovine serum and milk or colostrum. AB - Total (free plus protein-bound) and free cortisol concentrations in paired samples of serum and skim milk or colostrum were determined by specific radioimmunoassay after extraction or ultrafiltration. For 11 cows in established lactation mean total cortisol concentrations +/- SE in serum and milk were 4.5 +/ .7 ng/ml and .35 +/- .06 ng/ml, respectively. Concentrations of free cortisol in serum and milk were about .3 ng/ml, which is at the lower limit of the present assay. Following 200 IU Synacthen injection to 5 cows, total cortisol in serum and milk rose to 67 +/- 6.0 ng/ml and 11.4 +/- 1.5 ng/ml by 8 h postinjection, while free concentrations increased to 4.3 +/- .7 ng/ml and 6.5 +/- .8 ng/ml in serum and milk, respectively. Eight additional cows were sampled at 1 to 2 d after parturition, and total cortisol in serum and colostrum was 16.6 +/- 1.6 ng/ml and 4.4 +/- 1.3 ng/ml, and free cortisol was 2.4 +/- .4 ng/ml and 1.8 +/- .5 ng/ml, respectively. Free cortisol concentrations in colostrum or in milk from cows in established lactation, before or after adrenal stimulation, are directly related to free cortisol concentrations in the blood, while the bound cortisol in milk is more related to these two stages of lactation rather than the bound hormone in the blood. Measurement of free cortisol in milk should allow the monitoring of changes in plasma free cortisol in studies of stress in dairy cows. PMID- 4031198 TI - Stress and activity management: group treatment for cancer patients and spouses. PMID- 4031199 TI - Development of anticipatory nausea: a prospective analysis. PMID- 4031200 TI - Partner support and other determinants of smoking cessation maintenance among women. PMID- 4031201 TI - Longitudinal follow-up of unipolar depressives: an investigation of predictors of relapse. PMID- 4031202 TI - Personality test correlates of psychiatric case history data. PMID- 4031203 TI - Factor structure and correlates of ratings of inattention, hyperactivity, and antisocial behavior in a large sample of 9-year-old children from the general population. PMID- 4031204 TI - Depression Self-Rating Scale: utility with child psychiatric inpatients. PMID- 4031205 TI - Children's loneliness: a comparison of rejected and neglected peer status. PMID- 4031206 TI - Scale for the assessment of reality testing: reliability, validity, and factorial invariance. PMID- 4031208 TI - Comparison of external correlates of MMPI substance abuse scales across sex and race. PMID- 4031207 TI - Do alcohol expectancies mediate drinking patterns of adults? PMID- 4031209 TI - On the meaning of the WISC-R third factor: relations to selected neuropsychological measures. PMID- 4031210 TI - Cognitive bias and depression in psychiatrically disturbed children and adolescents. PMID- 4031211 TI - Peer-led program for the treatment and prevention of obesity in the schools. PMID- 4031212 TI - Effects of marital role problems and the self-concept on wives' depressed mood. PMID- 4031213 TI - Temperament characteristics of suicide attempters. PMID- 4031214 TI - Personality factors and change with multiple sclerosis. PMID- 4031215 TI - Contracting for treatment termination to reduce illicit drug use among methadone maintenance treatment failures. PMID- 4031216 TI - Solicitation of elderly depressives for treatment outcome research: a comparison of referral sources. PMID- 4031217 TI - Cognitive rehabilitation of memory functioning in amnesiac alcoholics. PMID- 4031218 TI - Faking good and faking bad on the Personality Inventory for Children-Revised, shortened format. PMID- 4031219 TI - Cautions in interpretation of comparisons between the WAIS-R and the Wechsler Memory Scale. PMID- 4031220 TI - The dissociation of an experience: the hidden observer observed. PMID- 4031222 TI - Behavioral compliance with direct and indirect body movement suggestions. PMID- 4031221 TI - Hypnotic hallucination alters evoked potentials. PMID- 4031223 TI - Hypnosis as a retrieval cue in posthypnotic amnesia. PMID- 4031224 TI - Social networks and developmental psychopathology: a comparison of adolescent children of a depressed, arthritic, or normal parent. PMID- 4031225 TI - Mania and low self-esteem. PMID- 4031226 TI - Obsessional personality traits and risk for bipolar affective disorder: an offspring study. PMID- 4031227 TI - Depressive symptoms among physically abused and psychiatrically disturbed children. PMID- 4031228 TI - Depressive self-schemas, life stress, and vulnerability to depression. PMID- 4031229 TI - The phenomenon of panic. PMID- 4031230 TI - Vietnam combat veterans with posttraumatic stress disorder: analysis of marital and cohabitating adjustment. PMID- 4031231 TI - Responses of psychophysiologic and subjective insomniacs to auditory stimuli during sleep: a replication and extension. PMID- 4031232 TI - A PIC profile typology of children and adolescents: 1. Empirically derived alternative to traditional diagnosis. PMID- 4031233 TI - Multiple personality: a social psychological perspective. PMID- 4031234 TI - Susceptibility to type A backward pattern masking among hypothetically psychosis prone college students. PMID- 4031235 TI - Social anhedonia in the prediction of psychosis proneness. PMID- 4031236 TI - Interpersonal competence among college men hypothesized to be at risk for schizophrenia. PMID- 4031237 TI - Low birth weight and ventricular enlargement in a high-risk sample. PMID- 4031238 TI - Span of apprehension deficits in children vulnerable to psychopathology: a failure to replicate. PMID- 4031239 TI - Applications of neuronal labeling techniques to the study of the peripheral auditory system. AB - Horseradish peroxidase (HRP) techniques have recently been applied to the study of the peripheral auditory system. These techniques make it possible to trace single, auditory-nerve fibers from their peripheral terminals on sensory cells to their central terminations within the cochlear nucleus. For the large, myelinated axons of type-I neurons contacting inner hair cells, HRP can be injected intracellularly through the same electrode used to record neural activity, allowing correlations to be made between structure and function on a single-cell basis. From these data, a cochlear frequency map has been constructed, and morphological correlates of differences in spontaneous discharge have been identified. For the small, unmyelinated axons of type-II neurons contacting outer hair cells, single-unit recordings have not yet been made; however, these neurons have been labeled by gross extracellular injections of HRP. Extracellular injections have also been used to study the peripheral terminations of single efferent neurons projecting to the outer hair cell region. The afferent fibers to the outer hair cell (OHC) region contact primarily OHCs from the third row, while efferent fibers primarily contact cells from the first row. Single efferent fibers innervate OHCs over a significantly larger cochlear length than single afferent fibers of either type. Possible functional interpretations of these morphological differences are discussed. PMID- 4031241 TI - Mathematical modeling of cochlear mechanics. AB - The recent discovery of oto-acoustic emissions [see Zurek, J. Acoust. Soc. Am. 78, 340-344 (1985)] and the newer measures of the micromechanics of the inner ear have generated renewed interest in quantitative descriptions of the biomechanics of the cochlea. Active elements (mechanical force generators) are thought to be essential for producing the high sensitivity and sharp tuning typically associated with normal cochlear function. A mechanical model with active elements is described which can simulate basilar membrane displacements with neural-like tuning and peak amplitudes of about 1 nm at the threshold of hearing. In addition, such models might help explain the source of oto-acoustic emissions. The paper describes the power of the recent attempts at providing quantitative descriptions and predictions of the mechanics of the cochlea. PMID- 4031240 TI - Acoustic emissions from the ear: a summary of results from humans and animals. AB - As mentioned in Saunders et al. [J. Acoust. Soc. Am. 78, 299-311 (1985)] an understanding of the transduction of sound into the auditory neural code is a major goal of the hearing scientist. A variety of tools has been and is being used to achieve that goal. The recent discovery of physical acoustic emissions from the ear provides both new insight into possible transduction mechanisms and a useful new tool for research. The existence of narrow-band spontaneous acoustic emissions from the ear suggests the possibility of active cochlear processes that were not seriously considered a decade ago. Acoustic emissions, both spontaneous and evoked, also provide a simple and noninvasive means of monitoring a by product of cochlear-mechanical activity. In the present paper, results of studies of acoustic emissions from human ears are briefly summarized and compared to results obtained with animals. Differences between human and animal emissions are noted and the implications of these differences and hypotheses to explain them are discussed. PMID- 4031242 TI - Patterns of organization in auditory cortex. AB - Previous work has described recently developed techniques that are contributing to advances in the study of the auditory system; some of these techniques have been used to make significant progress in this field. This paper includes a discussion of the tonotopic and binaural organizations of the auditory cortex (especially area AI), the neuronal connections between auditory cortical fields, the relationships between the functional maps and the connectivity patterns, the nature of binaural processing within AI, and the techniques used to assess the structural and functional properties of this portion of the central auditory pathway. PMID- 4031243 TI - The owl's cochlear nuclei process different sound localization cues. AB - This paper discusses how the barn owl's brain stem auditory pathway is divided into two physiologically and anatomically segregated channels for separate processing of interaural phase and intensity cues for sound localization. The paper also points out the power of the "downstream" approach by which the emergence of a higher-order neuron's stimulus selectivity can be traced through lower-order stations. PMID- 4031244 TI - Central factors in the discrimination and identification of complex sounds. AB - The paper by Jesteadt and Norton [J. Acoust. Soc. Am. 78, 365-374 (1985)] described certain similarities between psychophysical and physiological measures of frequency selectivity. Although the hearing of naturally occurring sounds is dependent upon these peripherally based relationships, recent research has shown that other, more central, processes are also strongly involved in the perception of complex acoustic events. The present paper describes research on the discrimination of complex sounds other than those of speech or music. In contrast to the more peripherally determined limits on the listener's sensitivity for single tones and other simple stimuli, the processing of complex sounds requires the interaction of peripheral and central mechanisms. These issues are discussed in relation to recent studies of the responses of the cochlea to speech stimuli. It is suggested that the peripheral processor may be relatively transparent to the essential spectral-temporal properties of speech, whereas more central processing severely limits the rates and amount of information that can be extracted from complex sounds. PMID- 4031245 TI - Speech perception: some new directions in research and theory. AB - The perception of speech is one of the most fascinating attributes of human behavior; both the auditory periphery and higher centers help define the parameters of sound perception. In this paper some of the fundamental perceptual problems facing speech sciences are described. The paper focuses on several of the new directions speech perception research is taking to solve these problems. Recent developments suggest that major breakthroughs in research and theory will soon be possible. The current study of segmentation, invariance, and normalization are described. The paper summarizes some of the new techniques used to understand auditory perception of speech signals and their linguistic significance to the human listener. PMID- 4031246 TI - Influence of following context on perception of the voiced-voiceless distinction in syllable-final stop consonants. AB - This paper reports acoustic measurements and results from a series of perceptual experiments on the voiced-voiceless distinction for syllable-final stop consonants in absolute final position and in the context of a following syllable beginning with a different stop consonant. The focus is on temporal cues to the distinction, with vowel duration and silent closure duration as the primary and secondary dimensions, respectively. The main results are that adding a second syllable to a monosyllable increases the number of voiced stop consonant responses, as does shortening of the closure duration in disyllables. Both of these effects are consistent with temporal regularities in speech production: Vowel durations are shorter in the first syllable of disyllables than in monosyllables, and closure durations are shorter for voiced than for voiceless stops in disyllabic utterances of this type. While the perceptual effects thus may derive from two separate sources of tacit phonetic knowledge available to listeners, the data are also consistent with an interpretation in terms of a single effect; one of temporal proximity of following context. PMID- 4031247 TI - Masking-period patterns: presentation of a model compatible with an enlarged set of psychophysical and physiological results. AB - Masking-period patterns (MPP) have been regarded by Zwicker [J. Acoust. Soc. Am. 59, 166-175 (1976)] as psychoacoustic equivalents of period histograms (PH) measured in auditory neurons. Various models have been proposed in the literature to account for his results. We present here a set of results on the MPP produced by a 40-Hz triangular masker that cannot be reproduced by any of these models. This leads to the elaboration of a new model for predicting MPP assuming the existence of nonlinearities in the basilar membrane, and based on neural fast adaptation and rectification, and a simple detection device. This model is shown to be able to account for the whole set of available results, and thus to provide a good basis for the use of MPP as a psychoacoustic tool for the study of PH. PMID- 4031248 TI - Additivity of simultaneous masking, revisited. AB - Lutfi [J. Acoust. Soc. Am. 73, 262-267 (1983)] compared simultaneous masking functions (signal threshold versus masker level) for individual sinusoidal and narrow-band noise maskers, and for those maskers presented in pairs. Lutfi found that the pairs of maskers produced 10-17 dB "excess" masking over that predicted from the linear sum of their individual masking and explained the results in terms of a model in which the effects of the maskers are summed after undergoing independent compressive transformations. This paper describes experiments similar to those of Lutfi, and presents evidence suggesting that Lutfi's results may have been influenced by two factors: (1) combination-product detection, and (2) the use of different detection cues for single maskers and for pairs of maskers. Experiment I showed that when the stimulus conditions were chosen so as to minimize the likelihood of combination-product detection, "excess" masking was only 3-5 dB. Experiment II supported the idea that for a single narrow-band noise masker, subjects make use of the relatively slow envelope fluctuations to enhance performance. When two independent narrow-band noise maskers are added, the effectiveness of this cue is reduced, and between 3 and 9 dB of "excess" masking occurs. When the two noises are derived from the same source, and have correlated envelope fluctuations, no "excess" masking occurs. The results indicate that Lufti's compressive-nonlinearity model clearly fails in some situations. PMID- 4031249 TI - Intensity difference limens at high frequencies. AB - Thresholds for amplitude modulation detection were obtained from four subjects at frequencies of 2, 4, 6, 8, and 10 kHz for sensation levels of 15, 30, 45, and 60 dB and modulation rates of 2, 4, and 8 Hz. High-frequency difference limens calculated from amplitude modulation thresholds were found to change nonmonotonically as a function of sensation level, independent of modulation rate. This nonmonotonic relation stemmed mainly from a gradual reduction of the difference limen at the lowest sensation level with increasing frequency. Difference limens for pulsed tone discrimination were also measured in two of the subjects at 2, 6, and 10 kHz and sensation levels of 15, 30, 45, and 60 dB. The relation between intensity discrimination and sensation level was similar to that found for amplitude modulation detection. These findings are interpreted as indicating that the nonmonotonic relation between sensation level and intensity resolution is a general characteristic of stimulus processing at higher frequencies. PMID- 4031250 TI - Lateralization of sinusoidally amplitude-modulated tones: effects of spectral locus and temporal variation. AB - It has long been recognized that listeners are sensitive to interaural temporal disparities (ITDs) of low-frequency (i.e., below 1600 Hz) stimuli. Within the last three decades, it has often been demonstrated that listeners are also sensitive to ITDs within the envelope of high-frequency, complex stimuli. Because these studies, for the most part, employed discrimination tasks, few data exist concerning the extent of laterality produced by ITDs as a function of the spectral locus of the stimulus. To this end, we employed an acoustic "pointing" task in which listeners varied the interaural intensity difference of a 500-Hz narrow-band noise (the pointer) so that it matched the intracranial position of a second, experimenter-controlled stimulus (the target). Targets were sinusoidally amplitude-modulated tones centered on 500 Hz, 1, 2, 3, or 4 kHz and modulated at rates ranging from 50 to 800 Hz. Targets were presented with either the entire waveform delayed or with only the envelope delayed. Our results suggest that: (1) for low-frequency targets, lateralization is influenced by ITDs in the envelope but is dominated by ITDs in the fine structure; (2) for high-frequency targets, envelope-based delays produce displacements of the acoustic images which are affected greatly by the rate of modulation; rather large extents of laterality could be produced with high rates of modulation; these data are consistent with those obtained previously in discrimination experiments; (3) for low rates of modulation (e.g., 100 Hz), delays of the entire waveform (both envelope and fine structure) produce much greater displacements of the acoustic image for low frequency than for high-frequency targets (where fine-structure-based cues are not utilizable); (4) there appear to be no consistent relations among extent of laterality, rate of modulation, and the frequency of the carrier within and across listeners. PMID- 4031251 TI - Localization of sound in rooms, II: The effects of a single reflecting surface. AB - Auditory localization was studied in a room bounded by a single acoustically reflective surface. The position of that surface was varied so as to stimulate a floor, a ceiling, and left and right side walls. The surface was eliminated in one condition so that we could examine localization in free field for purposes of comparison. Using a source identification method we assessed the influences of these various room configurations on the localization of both slow-onset and impulsive sine tones of low frequency (500 Hz). We also measured the steady-state interaural-time-difference (ITD) and interaural-intensity-difference (IID) cues available to subjects in the different room configurations and compared these data with the perceptual judgments. Our results indicate the following: (1) A sound must include transients if the precedence effect is to operate as an aid to its localization in rooms. (2) Even if transients are present the precedence effect does not eliminate all influences of room reflections. (3) Due to the interference of reflections large interaural intensity differences may occur in a room and these have a considerable influence on localization; this is true even at low frequencies for which IID cues do not exist in a free field. (4) Listeners appear to have certain expectations about the reliability and plausibility of various directional cues and perceptually weight the cues accordingly; we suggest that this may explain, in part, the large variation in time-intensity trading ratios reported in the literature and also the differing reports regarding the importance of onsets for localization. (5) In this study we find that onset cues are of some importance to localization even in free field. PMID- 4031252 TI - Vibrotactile forward masking: psychophysical evidence for a triplex theory of cutaneous mechanoreception. AB - Threshold shifts for the detection of vibrotactile test stimuli were determined as a function of the intensity of a masker. A 50-ms sinusoidal test stimulus was applied to the thenar eminence of the hand 25 ms after the termination of a 700 ms sinusoidal masker applied to the same site. The frequency of the test stimulus and the frequency of the masker were varied. To eliminate the influence of the Pacinian receptor system, stimuli were delivered through a 0.01-cm2 contactor. The results support the hypothesis that the detection of vibration delivered through a small contactor is determined by two separate populations of non Pacinian receptors. The study constitutes a psychophysical demonstration of the existence of three receptor systems responsible for the detection of vibration. PMID- 4031253 TI - Postnatal development of physiological responses in auditory nerve fibers. AB - The discharges of auditory nerve fibers in kittens 4-37 days of age were recorded from micropipette electrodes. Tuning curves, thresholds, and the degree of tuning (Q 10) are compared over this age range. The tuning curves for fibers during the first postnatal week are relatively flat, with thresholds above 100 dB SPL. The response areas of VIII-nerve fibers during this period are restricted to low-to middle frequencies. With increasing age there is a reduction in threshold and an increase in the sharpness of tuning which is dependent on fiber CF. Response characteristics similar to adult VIII-nerve fibers were observed first for fibers with CFs near 5 kHz. For the response measures used here, VIII-nerve fibers in kittens are adultlike by the third to fourth postnatal week. The results are discussed in relation to the morphological development of the cochlea reported by other investigators. PMID- 4031254 TI - Auditory brain stem responses from human infants: pure-tone masking profiles for clicks and filtered clicks. AB - The effects of simultaneous pure-tone maskers on ABR wave V latency and amplitude were examined in three-month-old infants as a means of delineating the frequency specificity of these responses in the immature auditory system. Masking profiles at two intensities (60 and 40 dBn HL) were obtained for click, as well as 4000- and 1000-Hz filtered-click stimuli. Infant profiles, obtained by measuring both latency and amplitude shifts as a result of the discrete-frequency maskers, were compared to adult data obtained under an identical masking paradigm. Both latency and amplitude analyses showed masking profiles for infants which reveal greater low-frequency contribution to responses than found in adult profiles. Additionally, the infant profiles reveal clear differences in the degree of high frequency spread of masking when comparisons are made to the adult data. PMID- 4031255 TI - Critique of "Measures of the sentence intonation of read and spontaneous speech in American English". PMID- 4031256 TI - Perceptual learning in frequency discrimination. AB - This study was concerned with the effects of training on the frequency discrimination ability of human listeners. Frequency discrimination at 200 Hz was tested before and after training. Four groups of listeners received training in four different frequency regions, 200, 360, 2500, and 6000 Hz. It was found that training at 200, 360, and 2500 Hz all provided comparable improvement in discrimination performance at 200 Hz whereas training at 6000 Hz provided less improvement. This result is consistent with the idea that frequency discrimination and pitch perception are mediated by different processes at high (greater than 5000 Hz) and low (less than 5000 Hz) frequencies. PMID- 4031257 TI - Transformation of sound-pressure level from the free field to the eardrum presented in numerical form. AB - In an earlier work [E. A. G. Shaw, J. Acoust. Soc. Am. 56, 1848-1861 (1974)], self-consistent families of curves which best fitted the experimental data from 12 studies were presented to show the average sound-pressure transformation from the free field to the human eardrum in the horizontal plane. Tabulated values of azimuthal dependence at 15-deg intervals in azimuth and transformation to the eardrum at 0 degree azimuth are given at 43 selected frequencies between 0.2 and 12 kHz. These values are self-consistent within 0.1 dB. PMID- 4031258 TI - The effect of segmental and suprasegmental corrections on the intelligibility of deaf speech. AB - Three experiments were conducted to study the effect of segmental and suprasegmental corrections on the intelligibility and judged quality of deaf speech. By means of digital signal processing techniques, including LPC analysis, transformations of separate speech sounds, temporal structure, and intonation were carried out on 30 Dutch sentences spoken by ten deaf children. The transformed sentences were tested for intelligibility and acceptability by presenting them to inexperienced listeners. In experiment 1, LPC based reflection coefficients describing segmental characteristics of deaf speakers were replaced by those of hearing speakers. A complete segmental correction caused a dramatic increase in intelligibility from 24% to 72%, which, for a major part, was due to correction of vowels. Experiment 2 revealed that correction of temporal structure and intonation caused only a small improvement from 24% to about 34%. Combination of segmental and suprasegmental corrections yielded almost perfectly understandable sentences, due to a more than additive effect of the two corrections. Quality judgments, collected in experiment 3, were in close agreement with the intelligibility measures. The results show that, in order for these speakers to become more intelligible, improving their articulation is more important than improving their production of temporal structure and intonation. PMID- 4031259 TI - Speech recognition in noise by individuals with mild hearing impairments. AB - The study was designed to test the validity of the American Academy of Ophthalmology and Otolaryngology's (AAOO) 26-dB average hearing threshold level at 500, 1000, and 2000 Hz as a predictor of hearing handicap. To investigate this criterion the performance of a normal-hearing group was compared with that of two groups, categorized according to the AAOO [Trans. Am. Acad. Ophthal. Otolaryng. 63, 236-238 (1959)] guidelines as having no handicap. The latter groups, however, had significant hearing losses in the frequencies above 2000 Hz. Mean hearing threshold levels for 3000, 4000, and 6000 Hz were 54 dB for group II and 63 dB for group III. Two kinds of speech stimuli were presented at an A-weighted sound level of 60 dB in quiet and in three different levels of noise. The resulting speech recognition scores were significantly lower for the hearing-impaired groups than for the normal-hearing group on both kinds of speech materials and in all three noise conditions. Mean scores for group III were significantly lower than those of the normal-hearing group, even in the quiet condition. Speech recognition scores showed significantly better correlation with hearing levels for frequency combinations including frequencies above 2000 Hz than for the 500-, 1000-, and 2000-Hz combination. On the basis of these results the author recommends that the 26-dB fence should be somewhat lower, and that frequencies above 2000 Hz should be included in any scheme for evaluating hearing handicap. PMID- 4031260 TI - Prior stimulation and the masking-level difference. AB - Signal detection in diotic (NoSo) and dichotic (NoS pi) conditions was measured as a function of the stimulus parameters of the noise that preceded the signal plus-masker. When the signal and masker were both pulsed, dichotic signal detection was worse than when the masker was continuous or when the onset of the masker preceded the signal-plus-masker by at least 500 ms. The dichotic detection thresholds decreased as the duration of the pulsed signal plus pulsed masker was increased. The level, spectrum, interaural configuration, duration, and temporal proximity of the prior noise (forward fringe) relative to the masker and/or signal and masker were all investigated. Almost any difference between the parameters of the fringe and the masker resulted in poorer signal detection in the dichotic conditions. These same stimulus conditions produced small (less than 2.2 dB) changes in the diotic detection thresholds. The various models of the Masking-Level Difference (MLD) may be modified to qualitatively describe some of these results. PMID- 4031261 TI - The comparative effects of signal sensation level and sound-pressure level on interaural time discrimination. AB - A series of experiments was performed to examine the extent to which precision of interaural time discrimination depends on the sound-pressure level (SPL) and/or sensation level (SL) of the signal. All experiments used a tone burst signal and a continuous white noise masker, which was either diotic or interaurally phase reversed. Results of the first experiment indicate that (1) at equal signal SLs, interaural time and intensity discrimination is more precise when measured with the added diotic noise, and (2) addition of the phase reversed noise, previously shown to cause less precise interaural time discrimination, has a similar effect on interaural intensity discrimination. In the second experiment, interaural time JNDs for a signal of constant SPL were measured as a function of noise level. Results show that a low-level diotic noise can benefit interaural time discrimination, particularly at 500 Hz. The third and fourth experiments were performed to measure interaural time discrimination as a function of increasing signal SPL but constant signal-to-noise ratio. The data show the JND decreasing with increasing signal SPL at nearly the same rate with or without the added noise, indicating that an increase in signal-to-noise ratio is not necessary for improved discrimination. PMID- 4031262 TI - Effects of frequency modulation on absolute, masked, and reflex thresholds. AB - Behavioral and acoustic reflex thresholds were determined for five normal-hearing subjects in response to carrier signals of 500 and 2000 Hz which were unmodulated or modulated sinusoidally at rates of 2, 20, and 200 times per second with frequency deviations (delta f) of 30, 100, and 300 Hz. Behavioral (absolute and masked) thresholds were determined using an adaptive two-alternative forced choice procedure. Acoustic reflex thresholds were determined by visual inspection of stored reflex waveforms. Frequency modulation was not found to exert a systematic effect at absolute threshold. Frequency modulation did affect threshold estimates systematically, but differentially, at masked threshold and acoustic reflex threshold. Increasing the frequency deviation of the modulation was associated with an increase in masked threshold and with a decrease in acoustic reflex threshold at both test frequencies. The findings are discussed in terms of critical band phenomena. PMID- 4031263 TI - Incidence of spontaneous otoacoustic emissions in children and infants. AB - Whereas some evidence indicates that spontaneous otoacoustic emissions (SOAEs) may be a manifestation of the normal functioning of an active feedback mechanism in the cochlea, other evidence suggests that emissions may be the result of the interaction of such a feedback mechanism with localized outer-hair-cell damage. The present study surveyed the incidence of SOAEs in children and infants. If SOAEs are correlated with outer-hair-cell damage, the incidence of SOAEs might be expected to be lower in these two groups than in adults. The results showed no difference in the incidence of SOAEs with age. They also showed a significant tendency for a higher incidence of SOAEs in females than in males. PMID- 4031264 TI - Derivation and implementation of air criteria during hazardous waste site cleanups. PMID- 4031265 TI - Time from onset of symptoms to thrombolytic therapy: a major determinant of myocardial salvage in patients with acute transmural infarction. AB - To determine whether myocardial salvage after successful intracoronary or intravenous thrombolysis is time dependent, the relation between left ventricular wall motion and the time to treatment was studied in 69 patients admitted less than 3 hours after onset of acute transmural myocardial infarction (42 patients with reperfusion by intracoronary streptokinase, 27 by intravenous urokinase). A similar significant relation between the time to treatment and the severity of regional hypokinesia at follow-up was found in the intracoronary and intravenous groups. To better define this relation, particularly during the early phase of infarction, the groups were combined. In patients in whom thrombolytic treatment was initiated within 2 hours after symptom onset, wall motion at follow-up was within 2 standard deviations of the normal mean in 82% (14 of 17 patients). If treatment was started 2 to 5 hours after symptom onset, the probability of improved wall motion decreased to 46% (24 of 52 patients, p less than 0.025). The time/wall motion relation appeared to be independent of infarct location, angiographically visible collateral vessels and the presence of subtotal coronary artery occlusion. The severity of hypokinesia at follow-up study correlated with the magnitude of peak serum creatine kinase (r = -0.71), indicating that thrombolytic therapy initiated within 2 hours after the onset of symptoms improves regional left ventricular function and reduces infarct size more than later therapy does. PMID- 4031266 TI - Systemic embolism in chronic left ventricular aneurysm: incidence and the role of anticoagulation. AB - The incidence and prevention of systemic embolism in patients with chronic left ventricular aneurysm have been controversial. This retrospective study investigated the incidence of clinically evident embolic events and the effect of oral anticoagulation in patients with unequivocal angiographically defined left ventricular aneurysm. Between 1971 and 1979, 76 patients met the ventriculographic criteria and received initial medical management. The median interval from myocardial infarction to ventriculography was 11 months (range 1 month to 16 years) and subsequent median follow-up time was 5 years. Twenty patients receiving anticoagulant therapy were followed up for a total of 40 patient-years and 69 patients not on anticoagulant therapy were followed up for a total of 288 patient-years; 13 patients were included in both subsets. Twenty eight patients died during follow-up and the 3 and 5 year survival rates were 75 and 61%, respectively. Only one patient not receiving anticoagulant therapy had a clinical embolic event, resulting in an incidence of 0.35 per 100 patient-years. Therefore, in the absence of other predisposing conditions, the extremely low incidence of systemic emboli in these patients with chronic (first documented at least 1 month after myocardial infarction) left ventricular aneurysm does not justify the use of long-term oral anticoagulant therapy. PMID- 4031267 TI - Comparison of high pulse repetition frequency and continuous wave Doppler echocardiography in the assessment of high flow velocity in patients with valvular stenosis and regurgitation. AB - Continuous wave Doppler echocardiography has proved useful in detecting and quantitating the high velocity flow disturbances that characterize many stenotic and regurgitant valvular lesions. Pulsed Doppler echocardiography, in contrast, is limited in its ability to quantitate the high velocities that are detected. Recently, new pulsed Doppler systems have been developed that employ high pulse repetition frequencies and can theoretically measure higher flow velocities than those measured by the standard pulsed Doppler systems. To determine the ability of high pulse repetition frequency Doppler echocardiography to accurately measure high velocity flow signals in comparison with the continuous wave method, 80 patients undergoing routine echocardiographic examination for the assessment of valvular heart disease were studied using both techniques. A total of 113 high velocity flow disturbances were detected in 68 patients. In 41 instances, the maximal velocities by the two methods were within 0.5 m/s of each other. In 68 of the 113 high velocity lesions, however, the high pulse repetition frequency technique underestimated the peak velocity found with continuous wave Doppler echocardiography by more than 0.5 m/s. Comparison of the peak velocities recorded by the two methods for the total group showed no significant correlation (r = 0.04, p = NS). Comparison of the difference in peak velocities obtained by the two techniques with the maximal continuous wave velocity (n = 94, r = 0.70, slope = 0.71) suggested that the underestimation becomes greater as the peak velocity increases. Fifteen of the study patients with aortic stenosis subsequently underwent catheterization.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4031268 TI - Interaction of "supplementary" scintigraphic indicators of ischemia and stress electrocardiography in the diagnosis of multivessel coronary disease. AB - Lung uptake, ventricular cavitary dilation and basal myocardial uptake represent abnormalities that have been associated with myocardial ischemia on stress thallium-201 images, but that are supplementary to the conventional assessment of perfusion distribution. These "supplementary" indicators of ischemia were related to the coronary distribution of perfusion abnormalities, the results of electrocardiographic stress testing and to the findings on coronary angiography in 73 patients. Forty patients had multivessel coronary disease; 19 of these had three vessel disease. Perfusion abnormalities were seen in 39 of these 40 patients but were indicative of multivessel coronary disease in only 28 and of three vessel disease in only 6. However, supplementary indicators were present in 33 of 40 patients with multivessel disease and in 15 of 19 with three vessel disease. Furthermore, they were seen in 16 of 22 patients with multivessel disease in whom conventional perfusion abnormalities underestimated the extent of disease, but in only 4 of 12 patients in whom the extent of disease was overestimated. The presence of either perfusion abnormalities in a multivessel distribution or supplementary indicators identified 38 (95%) of 40 patients with multivessel disease. A markedly positive electrocardiographic treadmill test was a less sensitive indicator of multivessel disease, appearing in only 15 of 40 patients. However, it was present in only 4 of 33 patients without multivessel coronary disease and was more specific for that diagnosis than were supplementary scintigraphic indicators (88 versus 67%, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4031269 TI - Peak regional acceleration: a method to identify subtle regional ventricular dysfunction from gated blood pool scans at rest in patients with coronary artery disease. AB - Peak regional acceleration images were obtained from gated blood pool scans at rest in 10 normal subjects, 16 patients who underwent cardiac catheterization for unstable angina or nontransmural infarction and were found to have normal ejection fraction and wall motion and 10 patients with prior infarction and regional dyssynergy. The second derivative of the time-activity curve of each pixel was generated and the maximal systolic value of the derivative for each pixel was displayed as a functional image (peak regional acceleration). Anterior and left anterior oblique views were evaluated for abnormalities and the presence and location of defects were correlated with the coronary anatomy. The scans from the 10 normal subjects were used to establish the normal range for regional second derivative values. Both gated blood pool scans and second derivative images showed regional abnormalities in all 10 patients with prior transmural infarction. Regional abnormalities were present in the second derivative images in the distribution of 17 of the 20 coronary arteries with greater than 50% stenosis; there were no regional abnormalities in the distribution of 7 of the 8 arteries with less than 50% stenosis. In addition, regional second derivative image abnormalities were present in 15 of the 16 patients with unstable angina and normal wall motion and global ejection fraction. These 16 patients showed regional abnormalities on second derivative images in the distribution of 19 of the 23 coronary arteries with significant stenosis and no regional abnormalities in the distribution of 21 of the 23 coronary arteries without significant stenosis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4031270 TI - Effects of left ventricular asynchrony on time constant and extrapolated pressure of left ventricular pressure decay in coronary artery disease. AB - To elucidate the effects of ventricular asynchrony with or without myocardial ischemia on the time constant of left ventricular pressure decay and asymptote, that is, the level to which pressure would decrease if isovolumic pressure decrease continued infinitely, left ventriculography and pressure measurements were investigated in 14 normal subjects and 25 patients with coronary artery disease. Ventricular asynchrony was quantitated by the segmental area-time curve. This study consisted of two parts. 1) After a right atrial pacing stress test, the time constant and asymptote remained unchanged in eight normal subjects. In 18 patients with coronary artery disease and pacing-induced angina, asynchrony increased, the time constant was prolonged (64 +/- 13 to 94 +/- 17 ms, p less than 0.01) and the asymptote decreased (-22 +/- 10 to -46 +/- 20 mm Hg, p less than 0.01) after the pacing. 2) During right ventricular pacing at 80, 100 and 120 beats/min in the patients, asynchrony increased and the time constant was prolonged (55 +/- 7 versus 70 +/- 10, 47 +/- 11 versus 66 +/- 19, 36 +/- 7 versus 53 +/- 13 ms, respectively, p less than 0.01 versus right atrial pacing), whereas the asymptote was unchanged in six normal subjects compared with the value during right atrial pacing at each pacing rate. In seven patients with coronary artery disease, right ventricular pacing at 80, 100 and 120 beats/min also produced an increase in the time constant, while the asymptote was unchanged. Thus, prolongation of the time constant of left ventricular pressure decay may result from ventricular asynchrony even in the absence of myocardial ischemia.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4031271 TI - Spatial R wave amplitude changes during exercise: relation with left ventricular ischemia and function. AB - Thirty patients who exhibited increased and 65 patients decreased spatial R wave amplitude during exercise testing were compared for left ventricular function and ischemic variables. Spatial R wave amplitude was derived from the three dimensional Frank X, Y, Z leads using computerized methods. All patients had stable coronary artery disease and they were classified into two groups: one that attained a higher (n = 48) and one a lower (n = 47) median value of maximal heart rate during exercise (161 beats/min). Within these two groups, patients with increasing or decreasing spatial R wave amplitude during exercise were analyzed for differences in oxygen consumption, exercise-induced changes in spatial R wave amplitude, ST segment depression laterally (ST60, lead X), ST displacement spatially, left ventricular ejection fraction at rest, change in left ventricular ejection fraction with exercise and thallium-201 ischemia during exercise. Significant differences were demonstrated only in exercise-induced spatial R wave amplitude changes (p less than 0.0001). There was no significant correlation between exercise-induced change in heart rate and change in spatial R wave amplitude in either the group with increasing or the group with decreasing spatial R wave amplitude. It is concluded that changes in spatial R wave amplitude during exercise are not related to ischemic electrocardiographic or thallium-201 imaging changes or to left ventricular ejection fraction determined at rest or during exercise. PMID- 4031272 TI - Myocardial perfusion imaging in humans by contrast echocardiography using polygelin colloid solution. AB - This study evaluated the myocardial contrast effect and safety of polygelin colloid solution selectively injected into the coronary arteries in 25 patients during two-dimensional echocardiography. Six patients (group I) had selective intracoronary injections of nonagitated and 19 (group II) of hand-agitated polygelin colloid solution. Myocardial contrast was seen on two-dimensional echocardiographic cross sections in three patients of group I and in all patients of group II; in 16 patients it was also seen on M-mode echocardiograms. The contrast effect lasted for 15 to 60 seconds. The intensity of myocardial opacification was not significantly influenced by the amount of polygelin colloid solution injected, heart rate or cardiac size. The total number of contrast enhanced segments after right and left coronary artery injections delineated the entire cross-sectional area in any given view. None of the patients developed symptoms during or immediately after the injections. One patient had transient second degree atrioventricular block after a right coronary wedge injection, one patient showed a QRS axis shift and two others had transient T wave changes. There were no aortic blood pressure changes and no significant serum enzyme (creatine kinase [CK], CK-MB fraction, glutamic oxaloacetic transaminase) elevation or alterations of left ventricular function assessed echocardiographically. It is concluded that hand-agitated polygelin colloid solution is a useful and safe intracoronary contrast agent for delineating myocardial perfusion areas on two-dimensional echocardiography in humans. PMID- 4031273 TI - Myocardial perfusion imaging by contrast echocardiography: where are we going? PMID- 4031274 TI - The newborn transitional circulation: a two-dimensional Doppler echocardiographic study. AB - To characterize changes in circulation after birth, 11 normal full-term infants were examined with two-dimensional and pulsed Doppler echocardiography. The initial examination was performed within 10 hours after delivery and serially for 3 days. Retrograde diastolic pulmonary artery velocities, which are evidence for a patent ductus arteriosus, were detected in 10 infants (91%) on day 1, in 2 (18%) on day 2 and in none on day 3. Retrograde systolic descending aortic velocities, which are evidence of flow from the aorta into the ductus arteriosus, were observed in 10 infants (91%) on day 1, 9 (81%) on day 2 and 7 (64%) on day 3. Persistence of the retrograde systolic velocity in the descending aorta in the absence of retrograde diastolic velocity in the pulmonary artery is consistent with physiologic ductal closure beginning near the pulmonary artery end of the ductus arteriosus. Localized turbulent retrograde systolic flow, proximal to the septal leaflet of the tricuspid valve and consistent with tricuspid insufficiency, was detected in six patients (55%) on day 1, in eight (73%) on day 2 and in seven (64%) on day 3. Thus, tricuspid insufficiency appears to be a frequent observation in healthy newborns. Normal Doppler velocities in the great arteries and across the tricuspid and mitral valves of newborns up to 3 days of age are presented. These normal measures of intracardiac flow velocities may be used for comparison to identify abnormal flow profiles in newborns with congenital heart defects. PMID- 4031275 TI - Functional aortic valve atresia in transposition of the great arteries. AB - The criterion for the diagnosis of functional atresia of a patient semilunar valve is met when the pressure in a ventricle remains lower than that in the related great artery throughout systole so that no forward flow can occur. Functional pulmonary valve atresia has been well recognized in infants with normally related great arteries and massive tricuspid valve incompetence. The cardiac physiology and anatomy of an infant with transposed great arteries and functional aortic valve atresia is reported for the first time. The peak systolic pressure in the right ventricle was 30 mm Hg and in the aorta 64 mm Hg. The causes for right ventricular incompetence were abnormalities of the tricuspid valve and hypoplasia of the ventricular free wall. Three other cases with similar ventricular anatomy and physiology but with anatomic atresia of the aortic valve are reviewed. The possibility that under these physiologic circumstances during fetal life functional atresia develops first, and that anatomic fusion of idle semilunar cusps develops as a secondary phenomenon, is discussed. PMID- 4031276 TI - Respiration-dependent ventricular pacing compared with fixed ventricular and atrial-ventricular synchronous pacing: aerobic and hemodynamic variables. AB - A pacemaker that adapts heart rate in response to the patient's metabolic requirements has been developed. The pacemaker uses breathing frequency and tidal volume as the indicators of physiologic demand. Maximal physical work capacity, anaerobic threshold, oxygen uptake (16 patients) and hemodynamic variables (9 patients) were assessed with fixed rate (VVI), atrial synchronous (VDT/I) and respiration-dependent ventricular (VVI-RD) pacing. All subjects attained their anaerobic threshold in stress tests with VVI pacing. The maximal physical capacity (p less than 0.001), work time to attain the anaerobic threshold (p less than 0.01) and oxygen uptake (p less than 0.001) were significantly greater with VVI-RD than with VVI pacing. The transition from the supine to the standing position was characterized by a significant increase of cardiac index at rest with both VDT/I and VVI-RD pacing as compared with VVI pacing. Progressive increments in the cardiac index and average left ventricular stroke work index were significantly different at submaximal and maximal exercise when VVI and VVI RD were compared. At maximal exercise, mean cardiac output was also significantly different: 10.21 +/- 2.5 (SD) liters/min with VVI, 11.2 +/- 0.8 liters/min with VDT/I (p less than 0.05) and 12.65 +/- 3.1 liters/min with VVI-RD (p less than 0.05) pacing. Maximal oxygen extraction values were greater with VVI and VVI-RD pacing than with VDT/I pacing. Pulmonary artery end-diastolic pressures at maximal exercise were within the normal range with the three different modes of pacing. In conclusion, there is a significant (25%) improvement in exercise performance with VVI-RD pacing as compared with VVI pacing.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4031277 TI - Variable effects of changes in flow rate through the aortic, pulmonary and mitral valves on valve area and flow velocity: impact on quantitative Doppler flow calculations. AB - Doppler echocardiographic methods for measuring volumetric flow through the aortic, pulmonary and mitral valves provide the cardiologist with several potentially interchangeable noninvasive methods for determining cardiac output. In addition, comparison of flow differences through individual valves offers the potential to quantitate shunt flow and regurgitant volumes. To date, however, no study has compared the relative accuracies of each of these flow measurements in a controlled experimental setting. Therefore, in this study, Doppler echocardiography was used to measure aortic, pulmonary and mitral valve flows in seven open chest dogs on right atrial bypass where forward cardiac output was precisely controlled with a roller pump. Correlations with roller pump output were better for Doppler measurements of aortic (r = 0.98, SD = 0.3) and mitral (r = 0.97, SD = 0.3) than for pulmonary (r = 0.93, SD = 0.5) valve flow. Interobserver reproducibility was also better for aortic (r = 0.94) and mitral (r = 0.97) than for pulmonary (r = 0.88) valve flow measurements. All valves showed flow-related increases in cross-sectional area, but the slope of this response was variable: 0.05, 0.16 and 0.21 for the aortic, the pulmonary and the mitral valve, respectively. Increased forward flow through the aortic valve, therefore, was manifested primarily by an increase in velocity, whereas increasing flow through the pulmonary and mitral valves produced more significant area changes with correspondingly smaller increases in the velocity component. Recalculation of Doppler-determined outputs, assuming a fixed valve area for the entire range of flows, resulted in a decreased correlation with roller pump output. Both velocity and valve area should be measured at each flow rate for greatest accuracy in volumetric flow calculations. PMID- 4031278 TI - Determination of cardiac output by echocardiographic Doppler methods: relative accuracy of various sites for measurement. PMID- 4031279 TI - Effects of experimental myocardial infarction on the ST segment response to tachycardia. AB - Prior studies have shown that tachycardia results in ST segment depression in dogs with chronic, gradual coronary occlusion. This response was compared with that produced by acute, total occlusion of the left anterior descending artery. Ten dogs served as controls; in another 10 dogs, an ameroid constrictor was implanted about the left anterior descending artery. This artery was acutely ligated in a third set of 10 animals, and in a final set of 10, the distal left anterior descending coronary vasculature was embolized by latex injection. Tachycardia was produced by atrial pacing from rates of 90 to 250 beats/min using implanted atrial electrodes. Electrocardiographic signals registered from 84 torso electrodes were used to construct body surface isopotential maps during the ST segment. In normal dogs, pacing increased repolarization potentials without shifts in spatial features. New and abnormal anterior negativity, correlating with significant ST depression, appeared at rates of 170 beats/min or faster in dogs with ameroid constriction. However, in both groups with acute occlusion that produced transmural myocardial infarction, tachycardia resulted in increases in anterior ST elevation and reciprocal ST depression. Specific findings demonstrated the lead dependency of the response to tachycardia and the greater than normal increase in potential magnitudes after infarction than in control cases. The similarity of the response with acute occlusion and with embolization suggested that the response to tachycardia after infarction was not dependent on coronary collateral function but may represent a direct electrophysiologic effect of rate. Thus, these acute occlusion models simulate exercise-induced ST segment elevation as it may be seen clinically. PMID- 4031280 TI - Effects of verapamil and lidocaine in a canine model of sudden coronary death. AB - The efficacy of verapamil and lidocaine for treating ischemia-induced arrhythmias was determined in a conscious canine model with a previous myocardial infarction remote from the ischemic area. Temporary (up to 5.5 minutes) occlusion of the circumflex coronary artery was made in eight conscious dogs that had sustained an anterior myocardial infarction 13 to 35 days previously. Each dog served as its own control. Ventricular arrhythmias were observed in 100% of control experiments but in only 25% of experiments after verapamil pretreatment at 0.4 mg/kg body weight. Repetitive ventricular complexes, defined as two or more consecutive ventricular complexes terminating spontaneously in sinus rhythm, were seen in 88% of control experiments and 13% of verapamil experiments, whereas ventricular fibrillation was seen in 6% of control experiments but in no verapamil experiment. Thus, verapamil abolished arrhythmias or reduced the grade of arrhythmias in all dogs. Six of the eight dogs were also tested with lidocaine pretreatment at one or two doses resulting in mean plasma levels of 3.8 +/- 2.0 micrograms/ml. Ventricular arrhythmias were seen in 92% of control experiments and 100% of lidocaine experiments. The incidence of ventricular fibrillation increased from 8% in control to 60% in lidocaine experiments. It is concluded that verapamil may prevent severe ischemia-induced arrhythmias after a recent myocardial infarction, whereas lidocaine may in some cases aggravate arrhythmias. PMID- 4031281 TI - Defibrillator electrode-chest wall coupling agents: influence on transthoracic impedance and shock success. AB - The purpose of this study was to determine if the difference in transthoracic impedance produced by different coupling agents affects the success of shocks for defibrillation. Three different coupling agents, Harco pads (Hewlett-Packard), Littman pads (3M) and Redux paste (Hewlett-Packard), were assessed in 10 anesthetized dogs in which ventricular fibrillation was induced by electrical stimulation of the right ventricle. Defibrillation was attempted 15 seconds later, using 50, 100 and 150 joules (selected energy). Actual delivered energy, current, impedance and the percent of the shocks that achieved defibrillation were determined for the three coupling agents. Redux paste gave significantly lower impedance and higher current than the two disposable performed coupling pads tested. Despite this, there were no significant differences in shock success among the three coupling agents. Thus, in this experimental model, over a three fold energy range, disposable coupling pads were as effective as electrode paste for defibrillation despite the slightly higher impedance of the disposable pads. PMID- 4031282 TI - Functional and pathologic effects of multiple echocardiographic contrast injections on the myocardium, brain and kidney. AB - Myocardial contrast echocardiography can define in vivo the area at risk for necrosis after coronary occlusion. However, if this technique is to be used, it cannot be intrinsically toxic to the heart or other critical organs. To determine the functional and pathologic effects of contrast echocardiography, six intracoronary, six intrarenal and six intracarotid artery injections of 2 to 6 cc of a commonly employed contrast agent (agitated Renografin-saline solution) were performed in five dogs. A sixth dog served as a sham to assess any deleterious effects of the model preparation. Two-dimensional echocardiographic images and electrocardiograms were recorded during intracoronary injections, and heart rate, blood pressure, left ventricular end-diastolic pressure and rate of rise of left ventricular pressure (dP/dt) were continuously monitored. At 24 hours, echocardiographic and hemodynamic measurements were repeated, the dogs were killed and the heart, brain and kidneys were removed and prepared for light microscopic examination. Quantitative analysis of left ventricular wall motion was performed on control, peak contrast, post-contrast and 24 hour studies. With each intracoronary injection, there were transient decreases in blood pressure (p = 0.05 versus control) and increases in left ventricular end-diastolic pressure (p = 0.04 versus control). These were associated with depression of wall motion in contrast-enhanced regions (p = 0.01 versus control) and ST-T segment changes on the electrocardiogram. No significant change in heart rate or left ventricular dP/dt was noted. All variables normalized with the clearance of the contrast effect and remained normal to 24 hours. Light microscopic examination revealed no myocardial or cerebral changes attributable to the contrast agent injections.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4031283 TI - Cardiac function in patients with cystic fibrosis: evaluation by two-dimensional and Doppler echocardiography. AB - Two-dimensional and Doppler echocardiography were performed in 17 consecutive hospitalized patients with cystic fibrosis aged 6 to 38 years (mean 21 +/- 9) and in 10 normal subjects aged 24 +/- 7 years. Left ventricular and right ventricular ejection fraction were measured by a computerized light pen system and Simpson's rule from two-dimensional echocardiographic apical four and two chamber views. Right ventricular wall thickness, inferior vena cava size and the presence of tricuspid regurgitation by Doppler recording were also assessed. National Institutes of Health (NIH) score of clinical severity ranged from 22 to 72 (mean 51 +/- 15) (100 = excellent, 0 = poor). Four patients, all with an NIH score of 40 or less, died of respiratory failure within 1 year of the echocardiographic study. There was no significant difference between patients with cystic fibrosis and normal subjects with regard to right ventricular ejection fraction (59 +/- 11 versus 61 +/- 10%), left ventricular ejection fraction (67 +/- 8 versus 70 +/- 8%) and right ventricular systolic (5 +/- 1 versus 5 +/- 0.5 mm) and diastolic (2.4 +/- 0.5 versus 2.5 +/- 0.5 mm) wall thicknesses. A dilated inferior vena cava and mild tricuspid regurgitation by Doppler recording were detected in only one patient. A poor correlation was found between right ventricular ejection fraction and NIH clinical score (r = 0.26), chest X-ray score (r = 0.29) and pulmonary function tests. It is concluded that right and left ventricular systolic function is preserved in patients with moderately severe cystic fibrosis; clinical status in these patients is probably determined by the pulmonary rather than cardiac involvement. PMID- 4031284 TI - Lactate production during maximal and submaximal exercise in patients with chronic heart failure. AB - In patients with chronic heart failure whose cardiac output response to exercise is impaired, determination of anaerobic threshold may provide a useful and objective approach to grade the severity of heart failure. In such patients performing upright treadmill exercise to exhaustion, this study examined the reproducibility of the response of cardiac output and mixed venous lactate concentration when the exercise test was repeated the same or next day, the nature of this response after rest and exercise cardiac output levels were augmented by the cardiotonic agent amrinone and the response of lactate during symptom-limited submaximal exercise performed at either aerobic or anaerobic levels of work for each patient. Findings were: 1) the response of cardiac output and mixed venous lactate was reproducible (p less than 0.05) when assessed either the same or the next day; 2) when exercise cardiac output was increased (p less than 0.05) by oral amrinone therapy, the increase in lactate was delayed (p less than 0.05) to higher levels of muscular work and this was not true when cardiac output was unchanged; and 3) only submaximal anaerobic exercise was symptom limited and associated with an increase in lactate concentration. Thus, the lactate response and anaerobic threshold determination should prove useful to assess the severity of chronic stable heart failure and its response to pharmacologic intervention. The submaximal anaerobic exercise test may provide additional insights into the effort intolerance these patients experience. PMID- 4031285 TI - Methionine intolerance: a possible risk factor for coronary artery disease. AB - Homocystinuria, an inherited disorder associated with premature atherosclerosis, represents a severe form of methionine intolerance. To analyze the importance of milder forms of methionine intolerance in the genesis of vascular disease, the relation between provokable methionine intolerance and coronary artery disease was investigated. In a group of 138 men, aged 31 to 65 years (mean 53), referred for cardiac catheterization, plasma homocystine was measured before and 6 hours after an oral l-methionine load (0.1 g/kg). Thirty-nine subjects found to have normal coronary arteries had a mean post-load plasma homocystine level of 0.59 +/ 0.37 mumol/liter. A criterion at the 95th percentile (1.64 SD above the mean) was selected and applied to the remaining 99 subjects with coronary artery disease (0.70 +/- 0.68 mumol/liter). Sixteen (16%) of 99 subjects with coronary artery disease exceeded this level as compared with 1 (2%) of 39 subjects without coronary artery disease (p less than 0.04). The risk of coronary artery disease in men with provokable methionine intolerance was increased sevenfold as estimated by the odds ratio. By correlation matrix and multivariate regression analyses, provokable homocystinemia was predictive of coronary artery disease and was independent of tobacco smoking, hypertension, diabetes mellitus, serum cholesterol and age. It is proposed that men with mild methionine intolerance exposed to the high methionine content of the Western diet may develop intermittent homocystinemia and thus may be at greater risk for the development of coronary artery disease. PMID- 4031286 TI - Survival after hospital discharge in matched populations with inferior or anterior myocardial infarction. AB - Prognostic differences between patients with anterior or inferior myocardial infarction are often related to such variables as previous infarction or the size of the myocardial infarct. We examined the determinants of mortality in 997 hospital survivors of acute Q wave infarction (anterior in 449, inferior in 548) who, although not preselected, were well matched with respect to age, sex and prior infarction or congestive heart failure. Additionally, there was no significant difference in peak serum creatine kinase (CK) between the groups with anterior and inferior infarction (1,459 +/- 1,004 versus 1,357 +/- 1,036). Among the patients with anterior infarction who died during the 1 year follow-up period, 56% died in the first 60 days after hospital discharge compared with 18% of those without inferior infarction (p less than 0.01). Survival curves then became nearly identical at 3 months, and remained so until 1 year when the total mortality rate was 10% for the anterior and 7% for the inferior infarction group (p = NS). Variables associated with heart failure during the hospital phase were more prevalent in anterior infarction, but rales above the scapulae during the hospital stay (p less than 0.0001) and ventricular gallop at the time of discharge (p less than 0.0001) were the top two predictors of 1 year mortality by both univariate and multivariate analysis in inferior infarction. Age (p less than 0.0001) and peripheral edema (p less than 0.0001) were the strongest predictors of mortality in anterior infarction. Previous infarction, although just as common in the group with anterior infarction, was present at 1 year in 48% of nonsurvivors of the group with inferior infarction compared with only 19% of survivors (p less than 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4031287 TI - Echocardiographic findings in systemic amyloidosis: spectrum of cardiac involvement and relation to survival. AB - One hundred thirty-two patients with biopsy-proven systemic amyloidosis underwent echocardiographic examination to define the spectrum of cardiac involvement. Echocardiographic abnormalities were then correlated with clinical variables and survival at follow-up. Patients were subgrouped by left ventricular wall thickness: Group I, mean wall thickness 12 mm or less; Group II, mean wall thickness greater than 12 mm but less than 15 mm; Group III, mean wall thickness 15 mm or greater; or Group IV, atypical features such as wall motion abnormalities or left ventricular dilation. Patients with greater wall thickness had a higher frequency of associated echocardiographic abnormalities such as left atrial enlargement or granular sparkling appearance on two-dimensional examination and, more commonly, reduced systolic function. The occurrence of clinical congestive heart failure was strongly correlated with greater wall thickness and multiple other echocardiographic abnormalities. Survival was negatively influenced both by greater wall thickness and reduced systolic function. The median survival of the entire group was 1.1 years. Echocardiographic examination is an important tool for establishing the presence of cardiac amyloid involvement and may be useful in estimating prognosis in such patients. PMID- 4031288 TI - Smoke-like echo in the left atrial cavity in mitral valve disease: its features and significance. AB - In some patients with mitral stenosis, a smoke-like echo is observed in the left atrial cavity. The present study in 116 consecutive patients with rheumatic mitral valve disease investigated the echocardiographic features and clinical significance of this echo. The smoke-like echo is characterized by the following echocardiographic features: 1) it is composed of numerous microechoes; 2) it curls up slowly in the enlarged left atrial cavity; and 3) it vanishes as soon as it pours into the ventricular cavity. Hemostasis in the left atrial cavity was considered to be an important underlying condition for development of the echo. Hemorheologic conditions indicated that the shear rate of blood flow in the left atrial cavity was calculated to be low enough for the development of red blood cell aggregation. These conditions suggest that the source of the smoke-like echo might be aggregated cells due to hemostasis in the left atrial cavity. Left atrial thrombi were detected in many patients who had this echo in the left atrial cavity. Although it has not been conclusively determined that the presence of the smoke-like echo is a necessary condition for thrombus formation, this echo appears to be closely related to thrombus formation in the left atrial cavity. It is concluded that the presence of this echo indicates severe left atrial hemostasis and is a warning for thrombus formation. PMID- 4031289 TI - Continuous wave Doppler determination of right ventricular pressure: a simultaneous Doppler-catheterization study in 127 patients. AB - Simultaneous continuous wave Doppler echocardiography and right-sided cardiac pressure measurements were performed during cardiac catheterization in 127 patients. Tricuspid regurgitation was detected by the Doppler method in 117 patients and was of adequate quality to analyze in 111 patients. Maximal systolic pressure gradient between the right ventricle and right atrium was 11 to 136 mm Hg (mean 53 +/- 29) and simultaneously measured Doppler gradient was 9 to 127 mm Hg (mean 49 +/- 26); for these two measurements, r = 0.96 and SEE = 7 mm Hg. Right ventricular systolic pressure was estimated by three methods from the Doppler gradient. These were 1) Doppler gradient + mean jugular venous pressure; 2) using a regression equation derived from the first 63 patients (Group 1); and 3) Doppler gradient + 10. These methods were tested on the remaining 48 patients with Doppler-analyzable tricuspid regurgitation (Group 2). The correlation between Doppler-estimated and catheter-measured right ventricular systolic pressure was similar using all three methods; however, the regression equation produced a significantly better estimate (p less than 0.05). Use of continuous wave Doppler blood flow velocity of tricuspid regurgitation permitted determination of the systolic pressure gradient across the tricuspid valve and the right ventricular systolic pressure. This noninvasive technique yielded information comparable with that obtained at catheterization. Approximately 80% of patients with increased and 57% with normal right ventricular pressure had analyzable Doppler tricuspid regurgitant velocities that could be used to accurately predict right ventricular systolic pressure. PMID- 4031290 TI - Sustained ventricular tachyarrhythmias within 2 months of acute myocardial infarction: results of medical and surgical therapy in patients resuscitated from the initial episode. AB - Sustained ventricular tachycardia or fibrillation that develops during the early recovery period after acute myocardial infarction is a common clinical problem whose management remains controversial. Fifty-three patients who survived an initial episode of sustained ventricular tachycardia or fibrillation occurring between 3 and 60 days (mean +/- SD 21 +/- 16) after myocardial infarction were evaluated. Most of these patients had had a large (peak creatine kinase = 1,729 +/- 882 IU) complicated infarction. Forty-two (79%) of the 53 patients had had repetitive sustained ventricular arrhythmias and the condition of 19 of these could not be stabilized with drug therapy. Twenty-eight patients received medical therapy only. Twenty-four survived and were discharged from the hospital. Twenty five patients underwent infarctectomy or aneurysmectomy either on an emergency basis (16 patients) or electively because of coexistent heart failure or angina (9 patients). Intraoperative mapping was attempted in these patients but was completely successful in only 13 (52%). Operative mortality was 16% with all deaths occurring in patients who were in shock before surgery. Five of 21 surgically treated survivors required long-term antiarrhythmic therapy. Twenty one of 24 patients medically treated remain alive and well after 15 +/- 10 months of follow-up. Nineteen of 21 surgically treated patients remain alive and well after 17.9 +/- 11 months. One of these patients required reoperation for severe mitral regurgitation. These results confirm the poor medical prognosis of sustained ventricular tachyarrhythmias that present during the first 2 months after myocardial infarction but demonstrate that an acceptable rate of survival can be achieved with a combined medical and surgical approach to therapy. PMID- 4031291 TI - Malignant ventricular arrhythmias early after myocardial infarction: brighter prospects. PMID- 4031292 TI - Clinical evaluation of oral mexiletine therapy in the treatment of ventricular arrhythmias. AB - The effect of oral mexiletine therapy on ventricular arrhythmias was evaluated in 58 patients in whom conventional drugs had been unsuccessful. Mean daily dose of mexiletine was 652 mg (range 250 to 1,500) and mean duration of therapy was 14.4 months (range 0.1 to 34.4). Mexiletine was associated with a decrease of 52% in total premature ventricular complexes in 24 hours compared with control (6,841 +/ 1,053 [SEM] versus 3,248 +/- 734, p less than 0.005) and 19 patients (36.5%) had a greater than 83% decrease in ventricular ectopic rhythm. The drug was discontinued in 6 of these 19 patients because 5 of them (26%) experienced side effects after a mean period of 29.6 weeks (range 0.83 to 63.2) and sudden death occurred in 1 patient (5%); this indicates effective suppression of ventricular ectopic rhythm without significant side effects in 13 (25%) of 52 patients during long-term therapy. Adjustment of drug dosage to achieve therapeutic blood levels resulted in an efficacy on ventricular ectopic rhythm similar to that obtained with the maximal tolerated dose. There was no correlation between drug dose and therapeutic effectiveness. Mexiletine was associated with a 48% decrease in episodes of ventricular tachycardia (345.5 versus 179.3/24 h) and 5 of 10 patients with a history of cardiac arrest remained free of symptomatic ventricular tachyarrhythmias for 14.8 months (range 3.7 to 24.3).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4031293 TI - Potentiation by nifedipine and diltiazem of the hypotensive response after contrast angiography. AB - Arterial hypotension has been demonstrated after left ventriculography using currently available ionic contrast agents. This adverse hemodynamic response is significantly decreased with the newer nonionic contrast agents. Calcium channel antagonists also produce a hypotensive response. The potentially accentuated hypotensive response after bolus contrast angiography in patients receiving the calcium antagonists nifedipine and diltiazem was evaluated. Three contrast agents were compared: two ionic agents (Renografin-76 and Hypaque-76) and a nonionic agent (iopamidol). The hemodynamic response after left ventriculography was assessed in 125 patients, 65 receiving nifedipine or diltiazem and 60 not receiving these drugs. Baseline clinical characteristics were similar in all patient groups. The hypotensive response was significantly greater after left ventriculography with the ionic agents than with the nonionic agent. In those patients receiving nifedipine or diltiazem, the hypotensive response after bolus contrast angiography using the ionic agents occurred earlier after contrast injection (4.2 +/- 3.1 versus 12.9 +/- 6.0 seconds, p less than 0.0001), was more profound (maximal decrease in systolic arterial pressure, 48.5 +/- 13.9 versus 36.9 +/- 13.1 mm Hg, p less than 0.001) and was more prolonged (62.3 +/- 11.0 versus 36.4 +/- 12.0 seconds, p less than 0.0001) than in patients not receiving these drugs. A comparison of the two ionic contrast agents showed no significant difference in the hypotensive response. There was no difference in the hemodynamic response after angiography among patients receiving iopamidol alone and those receiving iopamidol and calcium antagonists. Thus, patients receiving the calcium antagonists diltiazem and nifedipine and undergoing left ventriculography with ionic contrast agents are at added risk for accentuation and prolongation of the hypotensive response. PMID- 4031294 TI - Lack of objective improvement in ventricular systolic function in patients with myocarditis treated with azathioprine and prednisone. AB - Six patients with myocarditis documented by biopsy, after a baseline right heart catheterization and echocardiogram, underwent treatment with azathioprine and prednisone. After 3 months of treatment, biopsy, right heart catheterization and echocardiogram were repeated. In addition to the immunosuppressive therapy, most patients received additional conventional medications for heart failure between evaluation periods (mean number of cardiac drugs increased from 1.7 +/- 1.0 to 2.7 +/- 0.05, p = 0.041). Mean heart rate decreased (105 +/- 14 to 84 +/- 13 beats/min, p = 0.016), as did pulmonary wedge pressure (23 +/- 8 to 12 +/- 4 mm Hg, p = 0.012). There were no significant changes in cardiac index (3.1 +/- 0.8 to 2.9 +/- 1.0 liters/min), end-diastolic dimension (62 +/- 13 to 62 +/- 12 mm) or fractional shortening (11 +/- 6 to 12 +/- 3%) with treatment. Complications from immunosuppressive therapy included severe soft tissue infection, acute psychosis and adrenal insufficiency in one patient each. The benefits from prednisone and azathioprine in this group of patients have not been demonstrated. Although heart rate and pulmonary wedge pressure decreased, these changes could be ascribed to increases in the conventional therapy for heart failure. Finally, there is a high incidence of side effects from prednisone and azathioprine therapy. These findings suggest that this unproven therapy for myocarditis should be limited to experimental protocols. PMID- 4031295 TI - Amiodarone pulmonary toxicity: early changes in pulmonary function tests during amiodarone rechallenge. AB - Amiodarone is an investigational antiarrhythmic agent known to cause pulmonary toxicity. This report describes two patients with previous amiodarone pulmonary toxicity and complete resolution who at rechallenge 5 to 6 months later developed within 2 weeks of therapy a significant reduction in lung diffusion capacity before overt clinical toxicity occurred. This suggests that toxicity may present early with reduction in diffusion capacity and that such changes may warrant the need to alter treatment. PMID- 4031296 TI - Amiodarone and the American Way. PMID- 4031298 TI - Early infarct expansion: structural or functional? AB - With the onset of ischemia, the length of myocardial segments increases rapidly, distorting ventricular geometry. Permanent stretching and thinning of infarcted zones have been termed infarct expansion. Although these changes are noted within minutes in vivo, infarct expansion may not be seen for days in postmortem preparations. The apparent postmortem reversal of early infarct expansion suggests that early expansion may be a functional phenomenon, reversible in the early hours of infarction. Alternatively, reversal of expansion may be a postmortem artifact, concealing the importance of underlying structural abnormalities. Myocardial infarction was produced in five dogs by occluding the left anterior descending coronary artery. Ultrasound sonomicrometers were used to measure myocardial segment end-diastolic length in the infarct and normal zones. After 3 hours of ischemia, the heart was arrested in diastole and biopsy specimens were taken from the normal and infarct zones. Sarcomere length was measured from electron photomicrographs, and myofiber width was measured from light photomicrographs. After 3 hours of ischemia, infarct zone segment length had increased significantly more than normal zone length (116 +/- 11 [SD] versus 103 +/- 4% of control length, p less than 0.05), whereas 2 minutes after cardiac arrest, both the infarct and normal zones returned to preischemic segment length, demonstrating apparent reversibility of early infarct expansion. However, histologic study revealed that the infarct zone myofibers were significantly thinner than normal zone myofibers (7.9 +/- 0.3 versus 9.4 +/- 0.3 micron, p less than 0.001) and sarcomere length in the infarct zone was significantly longer than that in the normal zone (1.9 +/- 0.2 versus 1.5 +/- 0.2 micron, p less than 0.005).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4031297 TI - Artifactual regional gray level variability in contrast-enhanced two-dimensional echocardiographic images: effect on measurement of the coronary perfusion bed. AB - The purpose of this study was to determine the extent of regional variability of image echocardiographic amplitude (expressed as gray level variability) in contrast-enhanced two-dimensional echocardiographic images, and to assess the effect of such baseline gray level variability on quantitation of the coronary perfusion bed. In 10 anesthetized closed chest dogs, short-axis papillary muscle echocardiographic images were obtained during control preinjection conditions and during injection of three contrast agents into the left main coronary artery with and without circumflex artery occlusion. Regional echocardiographic amplitude variation was measured by computer-based videodensitometric analysis of mean gray levels in four myocardial regions after cavity (background) gray level subtraction. To determine the effect of regional gray level variability on quantitation of the coronary perfusion bed, the contrast-enhanced left anterior descending artery perfusion bed was measured by two methods. The circumferential method ignored myocardial contrast inhomogeneity by measuring the circumferential extent of contrast enhancement, whether or not the enhancement by contrast medium extended transmurally. The exact method measured only the area of myocardium actually enhanced by contrast medium, which often did not extend transmurally. The perfusion beds determined by the two echocardiographic methods were compared with the anatomic perfusion bed determined by postmortem barium-gelatin coronary arteriography. Regional gray levels varied qualitatively and quantitatively in the control state (before contrast injection), with lateral regions being less bright than axial regions. After injection of contrast medium, brightness increased in all regions, the axial regions brightening most.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4031299 TI - Effects of a new nonionic and a conventional ionic contrast agent on coronary sinus ionized calcium and left ventricular hemodynamics in dogs. AB - Transient myocardial depression associated with intracoronary injections of contrast medium has been attributed to hypertonicity and to calcium binding. To further assess the importance of calcium binding, a new technique for continuous monitoring of coronary sinus ionized calcium with an intravascular calcium selective electrode was used. With this calcium-selective electrode the effects of intracoronary injection in dogs of a conventional ionic contrast agent, sodium meglumine diatrizoate (Renografin-76), and a new nonionic agent, iohexol, were assessed and compared. Left ventricular pressure was measured with a micromanometer catheter. After bolus injection of 0.2 ml/kg body weight of Renografin-76 (n = 10), coronary sinus pCa increased by 0.27 from 2.98 +/- 0.02 to 3.25 +/- 0.03, indicating a decrease in ionized calcium from 2.0 to 1.1 mEq/liter. With iohexol (n = 9), pCa increased by only 0.05 +/- 0.01 (p less than 0.001), indicating a decrease in ionized calcium from 2.0 to 1.8 mEq/liter. Peak changes occurred approximately 6 seconds after injection. Renografin-76 caused a marked decrease in left ventricular systolic pressure (140 +/- 7 to 106 +/- 8 mm Hg) and in heart rate (122 +/- 7 to 101 +/- 5 beats/min) with an increase in end diastolic pressure (5 +/- 1 to 12 +/- 1 mm Hg), whereas iohexol did not significantly alter these variables. Using Renografin-76 with calcium added to achieve an ionized calcium level of 2 (n = 4), 4 (n = 4) or 6 (n = 4) mEq/liter, the changes in coronary sinus pCa were abolished and the hemodynamic changes attenuated. These findings indicate that Renografin-76 results in greater myocardial depression than the new nonionic agent iohexol.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4031300 TI - Mechanism of cardiovascular effects of contrast media: evidence for transient myocardial calcium ion imbalance. PMID- 4031301 TI - Energy metabolism in reperfused heart muscle: metabolic correlates to return of function. AB - An important question in energy metabolism of the reperfused, previously ischemic myocardium is whether the return of a normal tissue adenosine triphosphate (ATP) content is a prerequisite for normal rates of oxygen consumption (that is, ATP turnover) and cardiac function. To study this problem, isolated working rat hearts were perfused with bicarbonate saline solution containing glucose (10 mM) at near physiologic work load. After 20 minutes, hearts were made totally ischemic by clamping the aortic and atrial lines for 5, 10 or 20 minutes and then were reperfused for another 10 minutes. Heart rate, aortic pressure, cardiac output and myocardial oxygen consumption were measured continuously. Adenine nucleotides, phosphocreatine, glycogen and the products of glycolysis were determined in freeze-clamped tissue extracts. Functional recovery was assessed by return of aortic pressure and oxygen consumption to preischemic values. Time required for return of function after reperfusion was 90 seconds after 5 minutes and 124 seconds after 10 minutes of ischemia. No recovery was observed after 20 minutes of ischemia. Tissue ATP content decreased significantly at the end of 5 ( 38%) and 10 (-56%) minutes of ischemia and did not increase significantly at return of aortic pressure and oxygen consumption to preischemic values. Glycogen stores decreased by more than 50% at the end of 10 minutes of ischemia and did not normalize on recovery. In contrast to ATP or glycogen, the phosphocreatine content decreased to even lower levels at the end of ischemia, but returned to levels higher than the control level after recovery from 5 to 10 minutes of ischemia in association with return of function.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4031302 TI - Atrial flutter in the young: a collaborative study of 380 cases. AB - As children with cardiac disease grow older, atrial flutter becomes more prevalent. A collaborative study was performed in 19 institutions to determine the clinical characteristics of these children and the factors affecting prognosis. There were 380 patients with one or more electrocardiographically documented episodes of atrial flutter that first occurred between ages 1 and 25 years (mean age at onset 10.3). Episodes of flutter continued to occur for a mean of 2.5 years after the onset. Of the 380 patients, 60% had repaired congenital heart disease, 13% palliated congenital heart disease, 8% unoperated congenital heart disease, 8% an otherwise normal heart, 6% cardiomyopathy, 4% rheumatic heart disease and 2% other lesions. Overall, drugs were effective in eliminating atrial flutter in 58% of patients; specifically, amiodarone and digoxin plus quinidine were effective in 53%, digoxin alone in 44% and propranolol in 21%. Amiodarone was effective in seven (78%) of nine patients. Corrective surgery was performed after the onset of atrial flutter in 66 patients; in 52% the atrial flutter was easier to control or it resolved and in only 4% it was worse. At follow-up (mean 6.5 years), 83% of the patients were alive (49% without atrial flutter and 34% with atrial flutter) and 17% died (10% suddenly, 6% of nonsudden cardiac cause and 1% of noncardiac cause). Cardiac death occurred in 20% of those for whom an effective drug could not be found to eliminate atrial flutter compared with 5% of those who were treated with an effective drug (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4031303 TI - Left ventricular hyperkinesia at rest and during exercise in normotensive patients 2 to 27 years after coarctation repair. AB - The short- and long-term results of effective surgical repair of coarctation of the aorta on left ventricular mass and function in 48 patients were evaluated using echocardiography and stress-gated radionuclide angiography. Thirty-two of the 48 patients who had no additional cardiac problems and had technically adequate radionuclide angiograms form the basis for this report. Among these, three had mild systolic hypertension and none had significant aortic valve dysfunction. Age at the time of study ranged from 6.5 to 59 years (mean 27). Age at the time of surgery ranged from 3 months to 34 years (mean 12 years). Duration from surgery to the time of noninvasive study ranged from 2 to 29 years (mean 15). In the 32 patients, left ventricular mass was 120 +/- 20 g/m2, compared with a control value of 87 +/- 10 g/m2. Mean left ventricular ejection fraction was elevated to 69.2 +/- 1.6% at rest (control 60 +/- 1.3%) and 78.8 +/- 1.3% during exercise (control 70 +/- 1.7%) (p less than 0.01). The systolic ejection rate was significantly increased (p less than 0.01) and end-systolic volume significantly decreased (p less than 0.01) compared with values in control patients. There was no correlation between ejection fraction and either age at the time of surgery or years since surgery. These findings of hyperdynamic left ventricular function and increased left ventricular mass without apparent cause many years after coarctation repair raise important questions as to mechanisms, extension to other forms of afterload stress that have been surgically or medically relieved and long-term outcome. PMID- 4031304 TI - Intelligence and hypoxemia in children with congenital heart disease: fact or artifact? AB - Previous studies have reported lower intelligence for cyanotic than for acyanotic children with congenital heart disorders, a finding attributed to the degree of hypoxemia present. Several important variables have not been examined consistently, however, including coexisting neurologic or genetic disorders, definitive surgery, degree of sickness, age at testing sex and social class. The present study examined the relation of these variables to obtained intelligence measures for 82 consecutively admitted children, excluding children with abnormal neurologic examinations and those having received definitive surgery. Consistent with earlier reports, intelligence quotients for the acyanotic children (112.81 +/- 14.52 mean +/- SD) were significantly higher (t = 2.60; p = 0.006) than for the cyanotic group (103.50 +/- 15.81). Although sex, race and social class were not significantly different between the 28 cyanotic and the 54 acyanotic children, the cyanotic children were significantly sicker (x2 = 9.12; p = 0.005) and younger (t = 4.10; p = 0.001). However, when young and old children and the degree of sickness within cyanotic and acyanotic groups were compared, no significant differences were found. These findings demonstrate that intelligence differences between cyanotic and acyanotic children persist when the effect of neurologic abnormalities and definitive surgery is removed and remain despite the severity of sickness or child's age at testing. PMID- 4031305 TI - The Starr-Edwards valve. AB - This report reviews the results obtained with the current models of the Silastic ball valve, classifying the experience with the mitral and aortic models into the periods (formula: see text) before and after 1973. Valve failure is defined according to the Stanford method and includes any valve-related death or complication necessitating valve removal (there have been no mechanical failures). Comparison of the valve model used today with the same model used in the late 1960s shows that the results have improved dramatically, especially with regard to thromboembolism. The results obtained with valves implanted after 1973 compare favorably with those of other contemporary valves introduced in the early 1970s. PMID- 4031306 TI - A 6 year experience with the St. Jude medical valve: hemodynamic performance, surgical results, biocompatibility and follow-up. AB - After in vitro testing (confirmed in vivo) of three contemporary valve designs (St. Jude, Bjork-Shiley and Carpentier-Edwards) demonstrated that the St. Jude valve possessed the most favorable hydrodynamic performance characteristics, a limited clinical trial was begun in high risk patients who might benefit from a prosthesis with improved hemodynamics. Between March 1978 and March 1984, 419 St. Jude prostheses (157 aortic, 156 mitral and 53 double aortic-mitral) were implanted in 366 patients. Ninety-six percent were in New York Heart Association functional class III or IV preoperatively. Early (30 day) mortality was 10.4% overall, and was lower after aortic (5.7%) or double (7.5%) than after isolated mitral valve replacement (16.0%). Forty-four prosthetic mitral valve recipients with severe ischemic mitral regurgitation experienced a 32% early mortality rate; without this group, mitral valve replacement carried a 10% early mortality rate (p less than 0.01). Multivariate logistic regression analysis confirmed that early death was strongly associated with three preoperative patient characteristics (p less than 0.05): ischemic mitral valve disease, depressed left ventricular function (ejection fraction less than 0.55) and advanced functional class (class IV). Late follow-up (7,055 patient-months, mean 22) was 99.7% complete (1 patient lost). Actuarial survival at 4 years was 80, 80 and 79% after aortic, mitral (nonischemic) and double valve replacement, respectively; in the subset with ischemic mitral regurgitation, actuarial survival was 34% (p less than 0.01). Eighty-six percent of survivors were in functional class I or II.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4031307 TI - Echocardiographic recognition of paraseptal structures. AB - Improved echocardiographic equipment provides detailed images of the heart and shows anatomic paraseptal structures previously not well defined. Echocardiograms were analyzed from 33 patients who later underwent cardiac transplantation, and the paraseptal structures noted were correlated with the pathologic specimens. Patterns associated with right ventricular chordae tendineae, the moderator band and the posterior papillary muscle are illustrated. Hypertrophic and fibrotic right ventricular trabeculae and left ventricular paraseptal bands are noted. These structures can be specifically sought and identified using the current generation of echocardiographs, thereby avoiding potential problems of septal definition and measurement. PMID- 4031309 TI - Pseudosimultaneous fast and slow pathway conduction: a common electrophysiologic finding in patients with dual atrioventricular nodal pathways. AB - Two ventricular responses following termination of rapid atrial pacing were noted in 24 of 87 patients with dual atrioventricular (AV) nodal pathways and supraventricular tachycardia. In all 24 patients, the AH intervals of the first and second ventricular responses were comparable with those of the fast and slow pathways, respectively. Careful analysis of the whole pacing sequence revealed that, in 21 patients, this phenomenon resulted from sustained slow pathway conduction with long AH intervals. In these patients, as the AH interval of each paced beat was progressively lengthened during pacing, the corresponding His bundle and ventricular responses were pushed one cycle behind the current atrial paced beat, so that the last paced beat was followed by two His bundle and ventricular responses. In only three patients did double ventricular responses result from simultaneous fast and slow pathway conduction. One of these three patients also showed two ventricular responses resulting from sustained slow pathway conduction. Several factors predispose to the occurrence of this phenomenon in patients with dual AV nodal pathways. These include an ability to sustain slow pathway conduction, a longer slow pathway AH interval, a shorter sinus AH interval (fast pathway) and a shorter atrial paced cycle length that sustains slow pathway conduction. In conclusion, sustained slow pathway conduction with resultant long AH intervals is the mechanism of two ventricular responses following termination of atrial pacing in most patients with dual AV nodal pathways. This phenomenon should be distinguished from the rare occurrence of double ventricular responses to an atrial impulse due to simultaneous fast and slow pathway conduction. PMID- 4031308 TI - Recognition of left coronary artery fistula to the left and right ventricles by contrast echocardiography. AB - A coronary-cameral fistula was inspected clinically by two-dimensional and pulsed Doppler ultrasound. At cardiac catheterization a fistulous connection between the left coronary artery and the right ventricle was observed. Contrast echocardiography using agitated saline solution injected into the aortic catheter clearly showed the passage of microcavitations into the left and the right ventricles confirming the connection of the fistula to both chambers. Contrast echocardiography is a valuable technique that can help define the site of drainage of coronary artery fistulas. PMID- 4031310 TI - Right coronary artery-pulmonary artery arteriovenous fistula secondary to open heart surgery. AB - A patient is described who underwent atrial septal defect repair at age 12 and presented 16 years later with angina. Coronary angiography revealed a right coronary artery to pulmonary artery fistula that had developed at the site of the previous thoracotomy. This is the first report of an acquired fistula of this type developing secondary to trauma associated with open heart surgery. Diagnosis, shunt quantification and treatment are discussed. PMID- 4031311 TI - Intractable heart failure, conduction disturbances and myocardial infarction by massive myocardial invasion of malignant lymphoma. AB - A patient with malignant lymphoma who developed congestive heart failure, conduction disturbances and myocardial infarction is presented. Two-dimensional echocardiography revealed marked thickening of the left ventricular wall, where the gallium scan correspondingly showed an abnormal accumulation. Irradiation to the mediastinum resulted in a dramatic decrease in ventricular wall thickness and disappearance of the gallium accumulation. Postmortem examination confirmed previous lymphomatous involvement of the myocardium. Combined techniques, including echocardiography and gallium scan, can be valuable for noninvasive detection and follow-up of myocardial involvement in patients with malignant lymphoma. PMID- 4031312 TI - Aneurysm of the interatrial septum. PMID- 4031313 TI - Ioxaglate, iopamidol and diatrizoate in coronary arteriography. PMID- 4031314 TI - Abstracts presented at the American College of Nutrition 26th annual meeting and the Fourth International Symposium on Magnesium. Blacksburg, Virginia, July 21 28, 1985. PMID- 4031315 TI - Steroid myopathy. PMID- 4031316 TI - Hypersensitivity reactions to ingested crustacea: clinical evaluation and diagnostic studies in shrimp-sensitive individuals. AB - Adverse reactions to ingested crustacea are common and may be life-threatening. We studied 14 individuals with histories of such reactions to shrimp by immediate skin tests and RAST with extracts of shrimp, crab, crayfish, and lobster. Nine of these subjects (8/8 atopics and 1/6 nonatopics) had positive immediate skin tests (wheal greater than or equal to 2 mm) and RAST (ratios greater than 3.0) to shrimp. Their skin tests and RAST ratios to the other crustacea were also frequently positive even, in several cases, in the absence of prior exposure. In contrast, only 1/10 volunteers with no history of intolerance to crustacea had a weak positive skin test to raw shrimp. These studies suggest that both skin tests and RAST are useful in the confirmation of hypersensitivity to shrimp in atopic individuals and that cross-reactivity among crustacea may exist. PMID- 4031317 TI - Cholinergic nasal hyperreactivity in atopic subjects. AB - Increased nasal secretions are a fundamental component of allergic rhinitis. In order to analyze various parameters of nasal secretions, a relatively nontraumatic method for collecting nasal secretions was required. A small, flexible rubber catheter connected to a vacuum and inserted 4 cm into the nose proved to be an efficient method for recovering secretions produced from a series of nasal washes. An average of 67% of the washings were recovered and analyzed for protein content. Topical methacholine (5 to 100 mg) stimulated a dose-related increase in the amount of protein secreted with atopic patients demonstrating significantly more responsiveness than nonatopic patients (29.9 times the prechallenge production of protein for atopic patients and 4.8 times for nonatopic patients). Pretreatment with atropine (10 micrograms) reduced the effects of methacholine in atopic subjects, indicating that the secretory activity was in response to muscarinic receptor stimulation. Therefore, in addition to the array of autonomic abnormalities already recognized in atopic patients, these subjects are also hyperresponsive to nasal cholinergic stimulation. PMID- 4031318 TI - Increased numbers of circulating basophil progenitors in atopic patients. AB - Recruitment of basophils to sites of homocytotropic antibody-mediated hypersensitivity reactions has been well documented in both experimental and clinical situations. Mechanisms underlying tissue basophil accumulation, however, remain unclear and may involve chemotaxis, cell proliferation, or both. We have recently reported the presence in human blood of circulating basophil/mast cell progenitors on the basis of histamine content of granulocyte colonies grown in methylcellulose. In the current studies we have analyzed the peripheral blood of 30 patients with atopy and 25 comparable control subjects for frequency of basophil/mast cell progenitors by analysis of the histamine content of individual granulocyte colonies. Forty percent of granulocyte colonies in cultures of atopic patients contained histamine in comparison to only 11% in cultures of control subjects (p less than 0.001). Histamine content per colony as well as mean histamine per cell in each colony was higher in granulocyte colonies of atopic subjects and could not be related to colony size or culture conditions. Granulocyte colony growth was enhanced by antigen-stimulated, peripheral blood lymphomononuclear cell--conditioned media of atopic patients. Histamine-positive colonies were found more frequently in active versus quiescent atopic disease (p less than 0.05). These results are consistent with the hypothesis that basophils accumulate at sites of allergic reactions at least in part by recruitment of progenitors from circulation and subsequent differentiation in situ in response to lymphokines. Further studies by use of hemopoietic assays could elucidate the contribution of basophil production to the development of allergic conditions. PMID- 4031319 TI - Skin testing with an aqueous extract of cotton bract. AB - Airway challenge with cotton bract extract (CBE) causes reversible bronchospasm in most volunteers never before exposed to CBE or the textile industry. Lung function abnormalities develop slowly after inhalation with a maximum effect reached within 2 hours and lung function slowly improving thereafter. When CBE was injected intradermally in three naive subjects with negligible airway response to CBE, we observed an initial wheal-and-flare reaction within minutes followed by erythema and subsequent induration that persisted for 24 to 48 hours. Microscopic examination of skin biopsy specimens obtained during the course of these reactions revealed edema in the early phase followed by perivascular infiltration of a mixed cellular nature in the subsequent stages of the reaction. Degranulation of mast cells was noted throughout the course of the reaction. These findings indirectly suggest that a nonspecific inflammatory reaction initiated by mast cell-derived mediators and sustained by the presence of infiltrating cells may be responsible for some of the airway effects observed in byssinosis. PMID- 4031320 TI - Where does cat allergen 1 come from? AB - Cat allergen 1, the major allergen from cats, has been demonstrated to be present in surface washing and in saliva. With the use of an immunohistologic technique with monospecific anti-CA 1, we demonstrated two different sources of the protein, mucous salivary glands and hair roots, where it originates from sebaceous glands. PMID- 4031321 TI - Congenital X-linked hypogammaglobulinemia and asymptomatic hepatitis B antigen carrier state. AB - Hepatitis occurring in patients with congenital X-linked or common variable hypogammaglobulinemia has been reported to follow a usual pattern of rapid progression from acute hepatitis to either chronic active hepatitis or death. This article describes a 21-year-old black man with congenital X-linked hypogammaglobulinemia who has been known to be a hepatitis B-associated antigen carrier during a 9-year follow up period. Liver enzyme studies are normal. His immunologic studies demonstrate no impairment of cellular immunity. His brother, who has the same disease and lives in the same household, has remained negative for hepatitis B-associated antigen. This patient demonstrates that not all hypogammaglobulinemia patients invariably have a severe clinical course with hepatitis. PMID- 4031322 TI - IgE against ethylene oxide-altered human serum albumin in patients with anaphylactic reactions to dialysis. AB - We have measured total antibody and IgE directed against ethylene oxide-altered human serum albumin (ETO-HSA) in the sera of 24 patients who have experienced anaphylaxis during hemodialysis and of 41 patients who have not had such episodes during hemodialysis. ETO is used to sterilize dialyzers and other medical equipment. The geometric mean level of IgE to ETO-HSA in patients with reactions (0.9 ng ETO-HSA bound to IgE per milliliter of serum) is significantly higher than in nonreacting patients (0.1 ng/ml, p less than 0.0001). Sixteen of 24 patients with reactions had detectable levels of IgE to ETO-HSA, whereas only three of 41 nonreacting patients had detectable levels (p less than 0.0001 chi square). The geometric mean level of total antibody to ETO-HSA is also significantly higher in patients with reactions (270 ng ETO-HSA bound per milliliter) than in nonreacting patients (31 ng/ml, p less than 0.0001). Fourteen of 24 patients with reactions but only four of 39 nonreacting patients had total antibody binding of ETO-HSA (p less than 0.0001 chi-square). These data extend our previous observations on a small group of 13 patients receiving hemodialysis (seven patients with reactions, and six nonreacting patients) and clearly demonstrate an association between the presence of IgE or total antibody to ETO HSA and immediate anaphylactic reactions in this group of 65 patients receiving hemodialysis. PMID- 4031323 TI - Allergic Aspergillus sinusitis. PMID- 4031324 TI - Approval by the Food and Drug Administration of polymerized ragweed extract for treatment of ragweed-sensitive individuals. PMID- 4031325 TI - Nutrition intervention: panacea or Pandora's box? AB - Past intervention efforts have not been effective in solving the nutrition problems in either industrialized or developing nations. While it may be intellectually stimulating, arguing over the subtleties of various strategies does not serve to improve the nutritional well-being of populations and may actually be detrimental. Whether we are concerned about an excess of calories or an inadequate supply of calories, the issue of calories is critical worldwide. A nutrient density approach provides a unified, scientifically justifiable, comprehensive approach to improving the nutritional status of populations in both developed and developing countries. PMID- 4031326 TI - Appalachian adolescents' eating patterns and nutrient intakes. AB - Meal and snack patterns of 114 male and 111 female adolescents in a southern Appalachian state were examined from 24-hour food records kept on a school day. Breakfast was skipped by 34% of the respondents, and 27% either skipped lunch or ate a snack-type lunch. The evening meal and snacks, each of which contributed about one-third of the daily energy intake, were eaten by 94% and 89%, respectively. Girls' mean intakes of vitamin A, calcium, and iron were low at all eating occasions throughout the day. Boys' mean intakes of iron were low at breakfast, lunch, and snacks; their vitamin A intakes were low at lunch and snacks. Adolescents who prepared their own breakfasts consumed less energy, protein, fat, and niacin at that meal than did adolescents who ate breakfasts prepared by their mothers. However, adolescent-prepared breakfasts were higher in nutrient density for calcium, riboflavin, and thiamin. Evening meals prepared by adolescents were similar in total nutrient content to meals prepared by their mothers but lower in nutrient density for iron and thiamin. Evening meals prepared by adolescents were more likely to include a sandwich and less likely to include a vegetable than were meals prepared by mothers. PMID- 4031328 TI - Health implications of obesity: an NIH Consensus Development Conference. AB - In February 1985, in Bethesda, MD, the National Institutes of Health held a Consensus Development Conference on the Health Implications of Obesity. Nineteen experts in pertinent subject areas presented the current state of the art to a panel of 15 senior-level professionals. On the basis of the scientific evidence presented and its discussion by the audience, the panel formulated a "consensus statement" of findings and recommendations in the form of a narrative reply to six key questions focused on the health implications of obesity. This article summarizes the results of the consensus conference and discusses the conclusions and recommendations of the panel and their implications for the dietetic profession. Also provided, as a practical tool for the dietitian, are two nomograms indicating body mass index and desirable weight and 20% and 40% overweight levels for men and women of different heights and weights. PMID- 4031327 TI - Prediction of total urinary nitrogen from urea nitrogen for burned patients. AB - Although many of the current nutrition assessment techniques are inappropriate for burned patients, we have found nitrogen balance to be a helpful measure of the effectiveness of nutrition therapy if it is used in conjunction with other measures of nutritional status. Many clinicians suggest that a 24-hour urinary urea nitrogen (UUN) measurement, in addition to a correction term of 2 to 4 gm nitrogen, will accurately represent all nitrogen losses (urinary non-urea nitrogen, fecal, integumental). However, since no burned patients were used in the development of that method, its use may not be appropriate for burned patients. As an alternative to total urinary nitrogen (TUN), which is costly and time consuming, we have developed a simple way to predict TUN from UUN, percent initial total body surface area burn, and age for pediatric and adult burned patients. We propose that nitrogen balance may then be determined from the predicted TUN by an equation showing that nitrogen balance equals daily nitrogen intake minus predicted TUN plus fecal and normal nitrogen loss. PMID- 4031329 TI - Assessing the cancer risk from foods. AB - Assessing the carcinogenicity of a compound and then determining what dosage is appropriate for human beings is a complex process. Carcinogens act either by altering deoxyribonucleic acid (DNA) or by promoting the growth of already altered cells. Carcinogenicity is evaluated with the use of structural analysis, in vitro mutagenesis assays, epidemiological findings, and dose-response studies in laboratory animals. In the animal studies, high doses are administered. Once a compound is found to be carcinogenic, the dose that will pose an acceptable cancer risk to human beings--one in a million--must be extrapolated from the high dose data. This virtually safe dose (VSD) will be the allowable dosage for human contact. The extrapolation from high-dose animal studies to a VSD for human beings is based on the models for carcinogenic mechanisms. Debate exists as to how many interactions with DNA the carcinogen must have to initiate neoplastic growth and whether there exists a threshold for carcinogenic action below which there is no risk of cancer. The extrapolation model that is chosen greatly affects the VSD. Knowing how this extrapolation to a VSD is done will help dietitians better understand how allowable levels for carcinogens in foods are determined. PMID- 4031330 TI - Food composition tables: recommended method for deriving nutrient values in their preparation. PMID- 4031331 TI - Energy and nutrient values from different computerized data bases. AB - Twenty-four dietary records were analyzed using three computerized nutrient data bases. Differences in mean values were found for 9 of 19 variables evaluated. No one data base consistently yielded highest or lowest values for all nutrients. Mean values appeared to be most consistent among the data bases for energy and the energy-yielding nutrients, calcium, phosphorus, and magnesium. Even when mean values did not differ significantly, values for some individual diets were widely discrepant. Whether comparisons of calculated energy and nutrient values are within or between studies and based on a few or many days of dietary information, values should be recognized as estimates and their limitations and strengths respected. PMID- 4031332 TI - Typical serving sizes: implications for food guidance. PMID- 4031333 TI - Acceptability of aspartame- and saccharin-sweetened fruits to users and nonusers of artificial sweeteners. PMID- 4031334 TI - Imaging the centenarian brain. A computed tomographic study. AB - Ten healthy and mentally alert centenarians underwent cranial computed tomography (CT) using a fourth-generation CT scanner. The subjects ranged in age from 100 to 102 years, and included six women and four men. Two of them used alcohol on a daily basis and five had systolic blood pressures of at least 160 mmHg. The CT scans demonstrated considerable variation in the degree of cerebral atrophy, which had no relation to either sex, alcohol use, or hypertension. Three of the centenarians had evidence of mild periventricular white matter lucency. Although progressive cerebral atrophy is an integral aspect of the normal aging process in the very elderly, its exact relationship to cognitive function remains unclear. PMID- 4031335 TI - Relationship between age at diagnosis and treatments received by cancer patients. AB - Increases in cancer incidence and mortality reflect the larger numbers of elderly in the population. Using a mortality sample of 1891 biopsy-confirmed cancer patients, analyses reveal older breast, prostate, and cervical-uterine cancer victims were more likely to be diagnosed with metastases. Logistic regression analyses of subsamples of breast (N = 224), lung (N = 513), and colorectal (N = 299) cancer patients indicate that age is significantly inversely related to receipt of both subsequent chemotherapy and radiation therapy, controlling for stage of disease and presence of co-morbid disease. Exceptions to this relationship are the use of radiation therapy among nonmetastatic lung cancer patients and all breast cancer patients. The implications of these findings for current cancer control programs are discussed. PMID- 4031336 TI - A 12-month fever surveillance study in a veterans' long-stay institution. AB - This report describes a 12-month fever surveillance survey in a 258-bed veterans long-term care institution. There were 128 episodes of fever (one episode per 24 patient-months); 114 were studied. Lower respiratory tract infections were most frequent, 36 (32%), with 26 (23%) urinary tract infections. Streptococcus pneumoniae was the most common pathogen in the chest infections and Proteus mirabilis the most common of the urinary tract infections. In 40 (35%) there was no evidence of a lower respiratory tract, urinary tract, or other bacterial infection. Most recovered rapidly, many with no specific treatment. There was a 16% mortality associated with the febrile episodes. PMID- 4031337 TI - Hospital readmissions among the elderly. AB - This paper investigates the six-month hospital readmission rates among 444 patients 65 years of age or older admitted to a large metropolitan teaching hospital who had a primary discharge diagnosis of cerebrovascular disease, hip fracture, or congestive heart failure. Twenty-four percent were readmitted to the same institution one or more times during the six-month follow-up. Striking variability was observed in use of hospitals across these diagnostic groups. Patients with a primary diagnosis of congestive heart failure were at highest risk of hospital readmission (36%). Multiple readmissions among the congestive heart failure group were prevalent. These preliminary data suggest that hospital readmission among the aged is a complex multifaceted phenomena. PMID- 4031339 TI - OARS methodology. A decade of experience in geriatric assessment. AB - The Older Americans Resources and Services (OARS) methodology was designed to assess functional capacity in five dimensions (social resources, economic resources, mental health, physical health, and activities of daily living) and to measure use of and need for 24 types of generic services. The OARS questionnaire now has been used in more than 150 research and practice settings. Recent refinements in the OARS methodology include new information about validity and reliability, computerized summary ratings for the five dimensions of functional status, and eleven scales that measure specific aspects of functioning within the five dimensions. This paper describes the conceptual foundation, appropriate uses, psychometric properties, and recent refinements in the OARS methodology. Empirical data from a geriatric clinic population are used for purposes of illustration. The paper presents an assessment of the strengths and limitations of the OARS methodology based on more than a decade of experience. Particular attention is paid to the degree to which the measures of functional status can be related to health service use measures to inform geriatric research and practice. PMID- 4031338 TI - Community-based geriatric assessment. AB - A comprehensive review of the multidisciplinary functional assessment and treatment of 800 patients seen at a community-based geriatric assessment center was performed to profile clinical characteristics of patients attending such a program and to evaluate possible predictors of institutionalization. The most common problems addressed were senile dementia (46%), hypertension (31%), clinically significant depression (30%), and burdened caregiver (24%). More than 90% of patients were able to remain in the community after multidisciplinary treatment of their problems and marshalling of support services. The most potent predictors of institutionalization in rank order of predictive value were: falls or unstable gait, senile dementia, caregiver strain, lack of support services, and moderate to severe impairment of ability to perform activities of daily living (multiple R = 0.45; P = .001). Advantages and impediments to community based assessment are discussed. PMID- 4031340 TI - Physicians' knowledge of prescribing for the elderly. A study of primary care physicians in Pennsylvania. AB - The 143 physicians who returned to Temple University Medical School a questionnaire on knowledge of prescribing for the elderly constituted 25% of a stratified random sample of general practitioners (GPs), family practitioners (FPs), and practitioners in internal medicine (IMs) reimbursed under Medicare in Pennsylvania in 1979. The mean score on the 23-item drug questionnaire was significantly lower (P less than .05) than the score deemed adequate by a panel of six experts in the field. Five variables, identified by survey questions, were positively associated with physicians' test scores: importance of professional meetings, perception of need for continuing medical education, board eligibility/certification, group practice, and a practice in which the elderly constitute 25 to 49% of all patients. Two variables were negatively associated: number of years since date of licensure and the importance of drug advertisements. Respondents and nonrespondents were compared on nine variables for which American Medical Association (AMA), American Osteopathic Association (AOA), or Blue Shield data were available. Pennsylvania graduates were significantly overrepresented in the respondent group. The only other significant difference found was in field of practice, where findings differed by source of information. There was no significant difference in mean scores of early and late respondents. The research findings support those of three previous studies, not limited to the elderly, which found prescribing knowledge inadequate. They suggest the need for examining/improving the opportunities for medical students and physicians to increase their knowledge of geriatric pharmacology. PMID- 4031341 TI - Sex, age, and values. PMID- 4031343 TI - OARS methodology and the "medical model". PMID- 4031342 TI - Geriatric assessment programs. Their time has come. PMID- 4031344 TI - Supporting each other. PMID- 4031345 TI - Career satisfaction and role harmony in Afro-American women physicians. PMID- 4031346 TI - Health care workers who breastfeed: implications for patient management. PMID- 4031347 TI - Women and science performance in a six-year medical program. PMID- 4031348 TI - Adolescent suicide: the tragic end of childhood. PMID- 4031349 TI - Pharmacology in optometry. PMID- 4031350 TI - Replacement of soft contact lenses. PMID- 4031351 TI - Trends in the change of clinical refractive error in myopes. AB - Longitudinal records of 559 myopes were obtained from five optometric practices. A linear regression model was used to describe various parameters of myopia progression, including onset age, rates, and cessation age of childhood progression. Typical rates of childhood myopia increases are around 0.4 D/yr, although there is considerable individual variability. An earlier onset is correlated with the development of a higher final amount of myopia. The earlier cessation age of childhood myopia progression in females than in males is hypothesized to be related to growth factors. PMID- 4031352 TI - Saccades and small-field optokinetic nystagmus in infants. AB - Developmental studies of infant eye movements may be a useful tool in the early diagnosis of visual abnormalities. We have measured saccades made by infants during the free scanning of stimuli differing in attentional value. When viewing stimuli with high attentional value, infants made saccades that had adult-like peak velocity/amplitude (main sequence) relationships, while for less interesting stimuli, their saccades were slower; saccadic oscillations were also more frequent for these stimuli. In studies of small-field horizontal and vertical optokinetic nystagmus, with binocular viewing, infants' horizontal OKN was of higher frequency and lower amplitude than their vertical OKN. Within vertical OKN, there was a clear asymmetry with reduced responsiveness to downward moving stimuli. This asymmetry declined for older infants; possible interpretations for this change are discussed. PMID- 4031353 TI - Development of stereopsis depends upon contrast sensitivity and spatial tuning. AB - Various binocular functions such as disparity vergence, and stereopsis develop rapidly during the third to fifth month of life. This time frame coincides with the rapid postnatal development of visual acuity, contrast sensitivity and possibly the tuning of spatial channels. Recent studies of adult stereopsis reveal that small disparities near the stereo threshold are processed within spatial channels tuned above 2.5 cycles/deg. Sensitivity to these higher spatial frequencies develops during the 3-5 months of life. Adult studies also reveal that larger disparities are processed by spatial channels tuned to lower spatial frequencies. Tuning of these low spatial frequency channels may not be present until 3 months of age. Lack of spatial tuning prior to 3 months is predicted to be associated with a lack of disparity tuning as well as an inability to ignore false disparities in ambiguous or redundant stimuli such as random dot stereograms. These observations suggest that refractive anomalies such as anisometropia that limit high frequency spatial resolution and binocular integration can present a major obstacle to the postnatal development of binocular vision. PMID- 4031355 TI - Hiring staff can be as serious as getting married. PMID- 4031354 TI - Forced-choice preferential looking acuity in very young kittens: a model for human development. AB - The development of visual acuity was studied longitudinally in young kittens, using a modification of the forced-choice preferential looking method (FPL). Acuity, defined as the spatial frequency which yields 70% correct responses by a naive observer, shows a 16-fold increase between 2 and 10 weeks of age. Acuity evaluated this way falls short of the acuity values obtained with the jumping stand or with electrophysiological methods. Acuity estimated with a criterion just above chance comes close to the resolution of the highest-resolving single cells in the striate cortex. PMID- 4031356 TI - Determination of reducing sugars in the nanomole range with tetrazolium blue. AB - Addition of sodium potassium tartrate to basic solutions of tetrazolium blue [(2,2',5,5'-tetraphenyl-3,3'-dimethoxy 4,4'-biphenylene) ditetrazolium chloride] greatly improved their efficacy as colorimetric reagents for reducing sugar determination. This modification increased sensitivity and decreased reaction time. The modified reagent can determine as little as 1 nmol of neutral sugars as well as 2-amino and N-acetyl amino sugars. PMID- 4031357 TI - Measurement of biophysical properties of red blood cells by resistive pulse spectroscopy: volume, shape, surface area, and deformability. AB - This paper presents a simple, new approach to the determination of size, shape, surface area, and deformability information for cells, notably red blood cells. The results are obtained by combining experimental measurements from resistive pulse spectroscopy (an extension of electronic cell-sizing methodology) with theoretical calculations for model cell systems. Assuming constancy of surface area and approximating red cell shapes by both prolate and oblate ellipsoids of revolution, values are determined for cell shape factor and volume under a variety of conditions. For red blood cells under low-stress conditions, shape factor, volume, and surface area results are found to be consistent with those available from the literature, when the oblate model is used. The applicability of this approach for determination of red cell properties under altered conditions is demonstrated by results for cell volume, at varying osmotic pressure and mechanical shear (tensile) stress. By quantitating the change in cell shape with stress, a new numerical scale for measuring cell deformability is also obtained, and data are presented on its variation for red cells at different osmolalities, over the range of 140 to 500 mOsm. PMID- 4031358 TI - Free fatty acid microdetermination by gas-liquid chromatography without transmethylating effects of methylation procedure. AB - A fast and practicable gas-liquid chromatographic method for the quantitation of non-esterified fatty acids (C14:0-C18:2) from 100 microliter plasma is described. This technique includes extraction, purification using the solvents n-heptane and 0.5 M Na2CO3, and methylation by 0.1 M HCl-methanol. Extraction, quantification and optimal methylation conditions without transmethylation have been investigated. Reproducibility is good and results agree with values found in the literature. PMID- 4031359 TI - A versatile technique for drying polyacrylamide slab gels. AB - Slab gels of different thickness, and of various homogeneous or gradient concentrations of acrylamide, can be dried rapidly and consistently using a newly developed drying procedure. After drying, stained gels retain excellent resolution of electrophoretic patterns, and unstained gels are suitable for use in autoradiography and fluorography. PMID- 4031360 TI - A polyvinylchloride-membrane based anion selective electrode for continuous registration of delta pH (interior alkaline) with salicylate as the indicator probe. AB - An anion sensitive electrode has been constructed with the use of the lipid soluble cation benzyl-dimethyl-hexadecylammonium analogous to the procedure described for tetraphenylphosphonium-sensitive electrodes [Shinbo, T., Kamo, N., Kurihara, K. and Kobatake, Y. (1978) Arch. Biochem. Biophys. 187, 414-422]. The anion electrode responds to salicylate concentrations above 400 microM with a Nernstian sensitivity. Less lipid soluble anions like chloride and phosphate do not interfere. Below 400 microM salicylate the response of the electrode decreases gradually so that the sensitivity of the electrode is less than 10 mV per decade change at concentrations of the anion of 50 microM. A computer program has been developed to fit the electrode response curve with a polynomal function of the fourth power. Additional software-allows calculation of changes in the concentration of the salicylate anion, also under conditions where the sensitivity of the electrode for the anion is not constant. In this way the electrode can be used to measure changes in salicylate concentration that occur in a suspension of bacteria when, upon energization, a pH gradient is generated. 31P nuclear magnetic resonance measurements demonstrated that the pH gradient measured with the salicylate-sensitive electrode in the phototrophic bacterium Rhodopseudomonas sphaeroides is quantitatively correct. The response time of the electrode decreases from 1 min at 20 microM salicylate to 10 s at concentrations greater than or equal to 200 microM. PMID- 4031361 TI - Horseradish peroxidase localization of the sympathetic postganglionic neurons innervating the cat heart. AB - The localization of the sympathetic postganglionic neurons innervating the cat heart has been investigated by using retrograde axonal transport of horseradish peroxidase (HRP). HRP was injected into the subepicardial layers of 4 different cardiac regions. The animals were sacrificed 72-96 h later and fixed by perfusion via the left ventricle. The paravertebral sympathetic ganglia from the superior cervical, middle cervical and stellate ganglia to T10 ganglia were removed and processed for HRP identification. Following injections of HRP into the apex of the heart, the sinoatrial (SA) nodal region and the ventral wall of the right ventricle, we observed that HRP-labeled sympathetic neurons were localized predominantly in the right stellate ganglia, and to a lesser extent, in the right superior and middle cervical ganglia, and left stellate ganglia. Fewer labeled cells were found in the right T4-T6. T8 and T9. After HRP injection into the dorsal wall of the left ventricle, HRP-labeled cells were present mainly in the left stellate ganglia. PMID- 4031363 TI - Selective hepatic vagotomy eliminates the hypophagic effect of different metabolites. AB - To test the hypothesis that vagally mediated metabolic signals from the liver affect feeding, we investigated the influence of selective hepatic vagotomy on the anorectic effect of different metabolites in rats. Subcutaneous injection of glycerol (GLY), D-3 hydroxybutyrate (DHB), L-malate (MAL), L-lactate (LAC), or pyruvate (PYR) (5.7 mmol/kg metabolic body weight = b.wt.0.75, each) reduced food intake in sham-vagotomized rats. Selective hepatic vagotomy eliminated the hypophagic effect of all metabolites. In an additional experiment, LAC retained its potency to inhibit feeding in sham-vagotomized rats after an intraperitoneal injection of atropine methylnitrate (5 mg/kg b.wt.0.75). The results demonstrate that the hypophagic effect of GLY, DHB, MAL, LAC and PYR originates in the liver and is mediated by hepatic vagal afferents. This implicates the existence of adequate hepatic receptors which might contribute to the control of food intake. PMID- 4031362 TI - Vagal afferent stimulation-evoked gastric secretion suppressed by paraventricular nucleus lesion. AB - Studies were performed to evaluate the possibility that the paraventricular nucleus (PVN) of the hypothalamus modulates gastric acid secretion by changing the sensitivity of the gastric secretory control mechanism to vagal afferent input. Under pentobarbital anesthesia, 17 rats were prepared with esophageal and pyloric catheters such that the stomach could be perfused continuously on a flow through basis. Thus, acid secretion could be monitored throughout the experiment. Stimulating electrodes were attached to the central cut end of the cervical vagus nerve. Unilateral stimulation of cervical vagal afferents resulted in a substantial increase in gastric acid secretion. This vagal afferent-mediated increase in acid outflow was suppressed following a single PVN lesion ipsilateral to the side of afferent stimulated output. Given the nature of PVN connections with brainstem regions responsible for the elaboration of vago-vagal reflexes, our results suggest that the PVN may control gastric acid outflow by changing the gain of gastric vago-vagal reflexes. PMID- 4031364 TI - The effect of cardiac autonomic blockade on ventricular response to changes in preload. AB - Echocardiographic (E) assessment of left ventricular response to increases (I) and decreases (D) in preload of 9 volunteer male subjects (mean age 25 +/- 2.0 years) was made during both control (C) and cardiac blocked (B) conditions. Cardiac autonomic blockade was produced by intravenous administration of atropine (0.04 mg/kg) and propranolol (0.2 mg/kg), while I was produced by 5 degrees head down tilt (T) for 90 min and D by lower body negative pressure to -40 Torr. Increases in resting heart rate of 44% and diastolic blood pressure of 13% occurred after B, (P less than 0.05). During C, the alterations in preload produced mean changes in end-diastolic volume (EDV) ranging from 135 +/- 10 cm3 for I to 96 +/- 9.1 cm3 for D. Changes in stroke volume during condition C were significantly related to changes in EDV during preload alterations and conformed to a normal LV function curve and were described by SV = 0.6 EDV + 4.5 cm3 (r = 0.85; P less than 0.001). Similarly during B, SV = 0.43 EDV + 5.8 cm3 (r = 0.75; P less than 0.001). Comparison of the LV function curves produced during C and B showed that both slope of regression and r were significantly different (P less than 0.01). These data indicate that cardiac autonomic blockade produces a downward shift in the LV function curve indicating a depression in myocardial contractility. In addition, the data indicate that changes observed in LV function during wide variations in preload are independent of autonomic nervous system influences and are independent of the intrinsic heart rate. PMID- 4031365 TI - Characterization of muscarinic cholinergic receptors in the submandibular gland of the rat. AB - The specific muscarinic ligand [3H]quinuclidinyl benzilate ([3H]QNB) was used to label acetylcholine receptors in the submandibular gland of the rat. Specific binding of [3H]QNB increased linearly with tissue concentration in the range of 0.02-0.3 mg of protein/ml. Kinetic analysis of [3H]QNB binding revealed the presence of a single population of high affinity binding sites, with a dissociation constant of 87.2 pM and a Hill coefficient of 0.95. The binding was saturable and the receptor density was 214 fmol/mg of protein. The rate constants at 37 degrees C for association and dissociation of the [3H]QNB-receptor complex were 5.98 X 10(-8) M-1 X min-1 and 6.6 X 10(-3) X min-1, respectively. The ratio k-1/k+1 gave a Kd value of 11.1 pM, similar to the Kd value (13.1 pM) determined by kinetic parameters when extrapolated at infinitely low receptor concentration. Muscarinic antagonists displaced [3H]QNB from muscarinic receptors with a Hill coefficient near to 1.0. Displacement curves for muscarinic agonists and for the atypical antagonist pirenzepine had Hill values significantly less than one. In the presence of 0.1 mM GPP(NH)P, the potency of agonists but not antagonists in displacing [3H]QNB binding decreased 2 to 3-fold. The [3H]QNB binding site was sensitive to the inhibitory effect of various sulfhydryl reagents. Repeated treatments of rats with an acetylcholinesterase inhibitor led to a decreased density of muscarinic receptors in the submandibular gland. This alteration was specific for the muscarinic recognition site and was paralleled by a reduced sensitivity to carbachol. PMID- 4031366 TI - Cardiac sympathetic nerve activity and progressive vasoconstriction distal to coronary stenoses: feed-back aggravation of myocardial ischemia. AB - This study tested the hypothesis that the relative ischemia distal to a severe coronary stenosis increases the activity of cardiac sympathetic nerves which in turn results in poststenotic vasoconstriction and an aggravation of ischemia. An acute severe stenosis which reduced coronary blood flow to 50% of control was produced in 23 anesthetized, vagotomized dogs and maintained for 20 min. The activity of postganglionic cardiac sympathetic nerves increased by 23 +/- 4% within 20 min. In parallel, poststenotic coronary resistance increased from 0.48 +/- 0.03 to 0.61 +/- 0.03 mm Hg X min X 100 g/ml resulting in a net lactate production after 15 min. Pretreatment with aspirin (6 mg/kg i.v.; n = 5) was without any influence on these reactions. The selective alpha 2-adrenoceptor antagonist rauwolscine (0.2 mg/kg i.v.; n = 6) and the calcium antagonist nifedipine (10 micrograms/kg i.v.; n = 6) prevented the progressive increase in poststenotic resistance and lactate production, but still permitted an increase in sympathetic activity. Segmental anesthesia of cardiac sympathetic nerves by epidural infiltration of procaine at segments C7-T6 (n = 6) prevented the sympathetic activation, the progressive increase in poststenotic resistance and the resulting myocardial ischemia. Sympathetic activation and a concomitant increase in poststenotic resistance resulting in myocardial ischemia were also found in 6 dogs with intact vagus nerves. These data support the hypothesis of a vicious cycle between poststenotic coronary vasoconstriction and sympathetic activation resulting in severe myocardial ischemia. PMID- 4031367 TI - The components of the hypogastric nerve in male and female guinea pigs. AB - A quantitative study has been made of the neural components of the hypogastric nerves of male and female guinea pigs using retrograde transport of horseradish peroxidase (HRP) to identify the population of neurones projecting in the nerve trunk, and electronmicroscopic analysis of the myelinated and unmyelinated axons present. Application of HRP to the transected axons of the hypogastric nerve labelled the cell bodies of sensory neurones in lumbar and sacral dorsal root ganglia, preganglionic neurones in the lumbar and sacral spinal cord, and postganglionic neurones in the inferior mesenteric ganglion and in the lumbar paravertebral chain; some ganglion cells of the pelvic plexus were also labelled. The number and distribution of each type of neurone with axons in the hypogastric nerve differed between the sexes: in particular, about twice as many preganglionic axons were present in the male as in the female. PMID- 4031368 TI - Tropic interactions between sympathetic nerves and vascular smooth muscle. AB - Explants of sympathetic ganglia from 3-9 day old rats were grown on collagen coated coverslips in modified Rose chambers for 5 days, either alone or 2 mm away from explants of 6 week old rat caudal artery and aorta. Nerve fibre growth was stimulated on the side of the ganglion explant near the caudal artery explants but was not stimulated near the aorta. To determine the source of the nerve growth stimulation, explants of whole intact wall of the caudal artery, separated adventitia and medial layers, enzyme-dispersed cells, homogenized cells and medium pre-conditioned by caudal artery explants, were combined with ganglia. Explants of whole caudal artery and dispersed cells were also precultured prior to combination with ganglia. These combinations allowed analysis of the role of smooth muscle cells, existing nerve fibres, necrotic cells and connective tissue. Results suggested that degenerating nerve fibres within the blood vessels caused the increase in the number and the 'attraction' of the nerve fibres growing from the sympathetic ganglia. In contrast, both caudal artery and aorta from 3-9 day old rats caused stimulation of nerve fibre growth. Since these vessels were not yet innervated, the effect cannot be due to degenerating nerve terminals and a different mechanism must be involved. PMID- 4031369 TI - Computer/video analysis of movement disorders. PMID- 4031371 TI - Enter the barefoot microscopist. PMID- 4031370 TI - Infection control and medical photography. PMID- 4031372 TI - The computing system in the Audio Visual Centre University of Newcastle upon Tyne. PMID- 4031373 TI - Videotapes for teaching clinical methods: medial students' response to a pilot project. PMID- 4031374 TI - Proper storage of photographic images. PMID- 4031375 TI - Interference from diathermy equipment during television recording of surgery. PMID- 4031376 TI - Effect of chronic bromocriptine administration on tumor size in patients with "nonsecreting" pituitary adenomas. AB - The effect of chronic bromocriptine administration (7.5-20 mg/day for 1-32 months) on the size of "nonsecreting" pituitary adenomas (NPA) was studied in 20 patients. Brain computed tomography showed a marked reduction of the adenoma in one patient after 1 month of treatment (7.5 mg/day); further scans taken 2 and 15 months later, under the same bromocriptine dose, did not show any other variations in the tumoral mass. In the remaining 19 patients, no changes in tumor size were documented by CT during the treatment. Four patients had a worsening of visual fields during bromocriptine administration and they were referred for neurosurgery. In conclusion, bromocriptine was ineffective in reducing tumor size in all but one patient with NPA and, in some cases, it did not prevent tumor growth as is suggested by the worsening of visual fields. Thus, bromocriptine treatment, at least at the doses capable of shrinking macroprolactinomas, seems to be of limited value in patients with NPA. PMID- 4031377 TI - Estradiol and progesterone receptors in normal and pathologic colonic mucosa in humans. AB - The presence of estradiol (E) and progesterone (Pg) receptors (R) has been demonstrated also in normal and neoplastic tissues known to be hormone independent and in particular in primitive colonic cancer, and, possibly, in healthy colonic mucosa. In this study endoscopic and surgical colonic mucosa specimens from 55 subjects were analyzed and divided as follows: 21 samples from healthy subjects, 12 normal mucosa samples from subjects affected with colonic cancer, 8 adenomatous polyps specimens, 5 samples from ulcerative colitis drawn on areas showing macroscopic lesions and 9 colonic cancer specimens. In the control group we have observed 6 cases positive for ER (28.6%) and 2 positive for PgR (14.3%). Six normal mucosa specimens from subjects affected with colonic cancer were found to be positive for ER (50%) and 2 for PgR (16.7%). Five colonic cancers resulted ER positive (55.5%) and 4 PgR positive (44.4%). Four polyps were ER positive (50%) and 3 PgR positive (37.5%); in this group only one subject showed positive binding in the surrounding normal tissue. These data confirm the presence of ER and PgR in colonic cancer and colonic adenomas (so-called precancerous disease); in these subjects the finding of steroid receptors also in normal mucosa suggests that the presence of steroid binding could be considered as a marker of a precancerous condition. PMID- 4031378 TI - Effects of growth hormone and triiodothyronine administration of the localization of 14C-D-glucose on regenerating sciatic nerve in rabbits. AB - In the present study the effect of the administration of GH and T3 on glucose distribution in the regenerating nerve was studied. The right sciatic nerve of 40 male rabbits was crushed at a specific site so that axonotmesis ensued. The animals were divided into two equal groups: one for the study of the effects of human growth hormone (hGH) and the other of triiodothyronine (T3). In all animals 14C-D-glucose a([14C]D-G) was injected iv as a tracer. The sciatic nerves from both sides were removed from all animals, divided into four equal segments and checked for radioactivity. In all cases an increased concentration of [14C]D-G appeared in the crushed nerve as compared with the intact one. GH administration caused a decrease in [14C]D-G uptake in both intact and injured nerves. T3 administration caused a significant decrease in [14C]D-G levels in the blood but did not substantially change [14C]D-G uptake in the crushed nerves as a whole. T3 administration appeared also to cause a peripheral displacement of the site of maximum [14C]D-G concentration in the injured nerve, indicating possibly an increased regeneration rate. PMID- 4031379 TI - Plasmatic arginine vasopressin levels in total and partial diabetes insipidus. AB - Plasma arginine vasopressin (AVP) was measured in 24 patients with polyuria exceeding 3.5 l/day diagnosed as severe or partial diabetes insipidus according to the dehydration test. All patients with severe diabetes insipidus diagnosed by the dehydration test had very low or undetectable basal AVP values and always subnormal plasma osmolality. Patients with partial diabetes insipidus diagnosed by the dehydration test had a wide range of AVP and osmolality values. The stimulation test performed on these patients was able to differentiate patients with primary polydipsia from patients with partial diabetes insipidus. The measurement of basal plasma AVP is capable of diagnosing all patients with severe diabetes insipidus; when we combine the stimulation test with the measurement of AVP, we can differentiate partial diabetes insipidus from other forms of polyuria. PMID- 4031380 TI - Estrogen and progesterone receptors in the human vagina. AB - Estrogen (E) and progesterone (Pg) receptor (R) levels were determined in the human vagina in relation to menopausal status, day of ovarian cycle and pregnancy. The results obtained confirmed that the human vagina contains ER and, in addition, demonstrated for the first time the presence of PgR in this organ in humans. In cycling women, ER and PgR did not vary significantly during the ovarian cycle; however low (less than or equal to 10 fmoles/mg cytosol protein) concentrations of PgR were more frequently (6 out of 8 cases) detected during the secretory phase. No substantial difference was seen in ER and PgR values between anterior and posterior wall of the vagina. In postmenopausal patients the levels of ER (range: 10-83 fmoles/mg) were similar to those found in premenopause (range: 12-78 fmoles/mg). As regards PgR, the majority (14 out of 20) of vaginae were devoid of PgR, 4 had a very low (less than or equal to 6 fmoles/mg) PgR content and only 2 cases had a PgR level higher than 10 fmol/mg cytosol protein. In pregnant patients (6th to 8th week) ER were found in all vaginae, while PgR were present only in some cases (3 out of 8). It was concluded that the behavior of ER in the human vagina seems different from that in the human endometrium, since ER levels do not vary in relation to changes in the concentrations of sexual hormones in the circulation. On the contrary, PgR levels appear to depend on blood estradiol and progesterone concentration, as in other target tissues. PMID- 4031381 TI - Effect of the new ergot derivative terguride on plasma PRL and GH levels in patients with pathological hyperprolactinemia or acromegaly. AB - Terguride, a derivative of lisuride, has been shown to possess a mixed dopaminergic-antidopaminergic activity in experimental models. We have studied the effects on PRL and GH levels of 0.2 mg po of terguride in 8 normal subjects, in 15 patients with pathological hyperprolactinemia (PHP) and in 17 patients with active acromegaly. In PHP, PRL levels were significantly reduced up to 300 min after terguride with a nadir (45 +/- 4.0% SE) significantly lower (p less than 0.05) than the one observed in the 8 normal subjects (72 +/- 3.5%). There was no significant difference in plasma PRL levels after 0.2 mg terguride or lisuride in 7 out of 15 patients tested with both drugs. Terguride did not significantly modify GH levels in PHP and in normals but when considering basal and peak (occurring between 60 and 150 min) GH values, a significant difference was found (p less than 0.01). Mean peak of GH did not differ significantly between PHP (5.0 +/- 1.1 ng/ml) and normals (6.8 +/- 1.7 ng/ml). Plasma GH levels of 17 acromegalics were not modified by 0.2 mg of terguride but were significantly reduced by 2.5 mg of bromocriptine. Terguride and bromocriptine reduced PRL levels in acromegalics (p less than 0.01) without any significant difference between the two drug. 0.2 mg terguride bid given for 15 days to 7 healthy volunteers significantly reduced both basal and sulpiride (25 mg im)-stimulated PRL levels. Side effects were observed only in 4 out of 47 subjects tested with terguride and in 8 out of 34 tested with bromocriptine. PMID- 4031382 TI - Clonidine-suppression test in epinephrine secreting pheochromocytoma: report of a case. AB - A patient is described in whom the diagnosis of pheochromocytoma was suspected on clinical grounds. He had normal urinary and plasma norepinephrine levels, with normal suppression of plasma norepinephrine by clonidine. However, plasma and urinary epinephrine levels were above normal, and plasma epinephrine was not suppressed but increased by clonidine. Selective venous sampling showed marked unilateral adrenal epinephrine excess. A large epinephrine secreting pheochromocytoma was surgically removed. This case suggests that, in pheochromocytomas releasing predominantly epinephrine, normal norepinephrine release from axon terminals of sympathetic postganglionic neurons is maintained and is suppressed by clonidine administration. It further reaffirms the value of plasma epinephrine estimations in the diagnosis of pheochromocytoma and indicates that normal suppression of plasma norepinephrine by clonidine does not preclude the presence of a predominantly epinephrine secreting tumor. PMID- 4031383 TI - Differential effects of acute DA receptor blockade with domperidone on LH and TSH release in patients with hyperprolactinemia. AB - Since dopamine (DA) has been implicated in the inhibitory control of both TSH and LH, we have compared TSH and LH levels following dopamine (DA) receptor blockade with domperidone in patients with hyperprolactinemia due to presumed prolactinomas. Eight euthyroid patients (aged 19-37 yr) with presumed prolactinomas each received domperidone (10 mg iv) at 11:00 and 23:00 h and tests were separated by at least one week. Basal TSH levels were significantly greater at 23:00 than at 11:00 h (2.7 +/- 0.5 vs 1.7 +/- 0.4 mU/l, mean +/- SE, p less than 0.01) whereas basal LH levels did not differ. All subjects showed clear rises in basal TSH levels following drug administration and these were significantly greater at 23:00 than at 11:00 h (p less than 0.02 at each time point). In contrast there was no alteration in LH levels following drug administration at either time of day. These data suggest that the mechanisms underlying the dopaminergic control of TSH and LH are different in these patients. Furthermore the data argue against an anterior pituitary or median eminence site of action of DA in the inhibition of LH release in hyperprolactinemia since domperidone does not penetrate the blood brain barrier to any appreciable extent. PMID- 4031384 TI - Lack of effect of im diazepam administration on hGH and hPRL secretion in normal and acromegalic subjects. AB - The usefulness of diazepam as a provocative stimulus for hGH secretion has been suggested as a simple, reliable test in clinical hGH assessment of pituitary disorders. We have investigated the effects of diazepam (10 mg im) on plasma hGH and hPRL in 5 normal and 7 acromegalic subjects. No significant variations in hGH and hPRL levels have been observed in any of the studied subjects. These findings indicate that the drug is ineffective on hGH and hPRL release and that it cannot be considered a valid provocative test either in normal or acromegalic subjects. PMID- 4031386 TI - More on nomifensine. PMID- 4031385 TI - Calcium metabolism of intact and thyroparathyroidectomized rats fed a bicarbonate enriched diet. AB - Rats fed a bicarbonate-enriched diet become alkalotic during their feeding period (ca. 10 h/day). Alkalosis produced a significant reduction in the plasmatic concentration of ionized calcium and increased parathyroid hormone secretion confirmed by concurrent hypophosphatemia and increased urinary excretion of cAMP. Three weeks of treatment produced, however, a significant reduction of bone Ca resorption. The increased endogenous fecal excretion of calcium counteracted the enhancement of true calcium absorption. No significant change in the skeletal calcium mass was observed. Thyroparathyroidectomized rats fed the alkaline diet reduced further their rate of bone Ca resorption and increased significantly their skeletal calcium mass. PMID- 4031387 TI - Role of blood osmolality in the regulation of vasopressin secretion in man: application of a new radioimmunoassay method for vasopressin. AB - A radioimmunoassay for plasma arginine vasopressin (AVP) has been developed based on R2 antibody of Thomas and Lee, synthetic standard (Ferring) and extraction on Sep-Pak column. High recovery of AVP (approximately 79%) was achieved with a detection limit of 0.25 pg/ml. By improving the technique of measurement of plasma osmolality an intraassay coefficient of variation less than 1% was obtained. Physiological studies performed with this method demonstrated that AVP becomes undetectable after water loading 20 ml per Kg of water po; (N = 6) and increases in response to hypertonic saline infusion (0.05 ml/kg/min; N = 15) with a linear relationship between plasma osmolality and AVP in individual subjects; this relationship is maintained when the test is repeated in the same subjects. However when pooling all data together, the relationship between plasma osmolality and AVP is best expressed by an exponential relationship. This implies that after AVP release is initiated, the concentration of the hormone increases more rapidly than plasma osmolality and the release is continuous possibly due to recruitment of increasing number of neuronal units whose osmotic threshold varies from individual to individual. PMID- 4031388 TI - Effects of relaxin on the mouse mammary gland. I. The myoepithelial cells. AB - Myoepithelial cells (MEC) were studied in the mammary gland of ovariectomized virgin mice without any hormonal treatment and following the administration of either estrogen or estrogen plus relaxin (either purified porcine relaxin standard or partially purified human relaxin extracted from decidua). Changes in MEC lineage were observed at both the light and electron microscopic levels in the hormonally treated animals as compared with the untreated controls. After 7 days of estrogen administration, there was a moderate elongation and branching of ducts. At the growing tips and buds undifferentiated precursors and promyoepithelial cells at various stages of their differentiation were seen with some frequency. After relaxin administration (18-20 hrs) to mice pre-treated with estrogen, branching and elongation of ducts were greatly increased as compared to mice treated with estrogen alone. At the growing points the ducts showed multi layered walls and undifferentiated precursors were quite frequently found with some mitotic figures. Moreover several promyoepithelial cells at various stages of differentiation were observed. These findings, which were similar after administration of the two different relaxin preparations, indicate a high rate of proliferation and differentiation of MEC in these experimental conditions and hence suggest that relaxin greatly enhances the de novo formation of MEC. A stimulatory effect of relaxin on MEC growth is discussed in terms of a possible role of this hormone in the genesis of benign and malignant neoplasms of the mammary gland, in which MEC proliferation can be recognized. PMID- 4031389 TI - Association of peroxidase enzyme defect and low thyroglobulin content in a case of endemic cretinism. AB - Neurological endemic cretinism is highly prevalent in severe endemic goiter areas. Often associated to euthyroid goiter, it is probably related to iodine deficiency. However the exact pathogenetic mechanism is yet unclear. We report the biochemical study of thyroid tissue obtained from a 26 year-old female cretin with a grade III multinodular goiter, neurological signs and euthyroidism. After surgery, thyroid tissue was analysed: iodoproteins where characterized by gel filtration, electrophoresis, sedimentation coefficient and antigenicity. Iodoalbumin was predominant while thyroglobulin was quantitatively reduced and poorly iodinated. In vitro, iodination with hog thyroid peroxidase was normal. There was no difference in peroxidase affinity for iodide in the oxidation reaction but a significantly reduced ability to iodinate in vitro thyroglobulin and free tyrosine. Oxidation of acetyltyrosilamide into bityrosine was also markedly reduced. These abnormal findings are known to occur in sporadic cases with or without hypothyroidism. The neurological defects could be linked to transient hypothyroidism during the critical period of nervous system maturation, however a role of iodine deficiency per se cannot be ruled out. PMID- 4031390 TI - Seasonal plasma profiles of testosterone and androstenedione in the Gentile di Puglia ram in southern Italy. AB - Seasonal plasma testosterone and androstenedione levels were determined by radioimmunoassay in the Gentile di Puglia ram. Androstenedione remains steady throughout the years, while testosterone shows seasonal changes. Testosterone is at high levels in winter, spring and summer and drops to a low concentration in autumn. PMID- 4031391 TI - Urinary 5 alpha-androstane-3 alpha, 17 beta-diol (5-Ad) determination in healthy children and adults. AB - The authors suggest a method for the evaluation of the urinary 5 alpha-androstane 3 alpha, 17 beta-diol (5 Ad) carried out by gas-liquid chromatography. 5-Ad is separated from its isomers, first by means of an adsorption chromatography on alumina and then by means of a high performance liquid chromatography on porous silica. The reliability criteria of the method have been studied according to the advice of the French Society of Clinical Biology. This method, applied to 175 healthy individuals of both sexes, grouped according to age starting from three years, allowed to determine the usual values of urinary excretion of 5-Ad in relation to age. PMID- 4031392 TI - International Symposium on "The Aging Process". Neuroendocrine and sexual aspects. Cosenza, 1981. PMID- 4031393 TI - Sexuality in aging: a study of a group of 300 elderly men and women. PMID- 4031394 TI - Sexuological problems in nursing-homes: a methodology for investigation. PMID- 4031395 TI - Prolactin influences sexual behavior during aging. PMID- 4031396 TI - Disappearance of opioid control of LH secretion in short term ovariectomized women. PMID- 4031397 TI - Adrenal-testicular interrelationships in the aging male. PMID- 4031398 TI - Fertility in elderly men. PMID- 4031399 TI - Gonadal senescence in the male. PMID- 4031400 TI - The physical fitness of elderly Nepalese farmers residing in rugged mountain and flat terrain. AB - This paper reports the results of a natural experimental test of the hypothesis that elderly residents of rugged terrains are more physically fit than their counterparts in flat terrains due to the additional lifelong daily exertion occasioned by the inescapable need to walk up and down steep slopes. Cycle ergometer tests of physiological response to work were undertaken by two groups of high caste Hindu male farmers, aged 50 to 79, living in Central Nepal. One comprised an experimental group resident in rugged terrain and the other a control group resident in flat terrain. No differences in heart rate and blood pressure measured at submaximal workloads, at peak effort, or during recovery from exercise were demonstrated. Measurements of physical exertion revealed that few people in either terrain engaged in activity sufficiently strenuous to raise heart rates to a level where training could occur. Despite a rural agricultural lifestyle, these men were not especially physically fit. PMID- 4031401 TI - Diagnostic evaluation of 200 elderly outpatients with suspected dementia. AB - A standardized diagnostic evaluation was performed on 200 consecutive patients over age 60 with suspected dementia. Diagnoses were confirmed by consensus and subsequently by follow up. Over 70% had Alzheimer's type dementia; 31% had more than one illness contributing to the dementia state, with overlap between the two groups. The most common so-called "treatable" illnesses were drug toxicity, hypothyroidism, and other metabolic diseases; 248 other medical diseases were recognized in 124 patients. Improvement occurred in 55 patients (27.5%) and persisted in 28 (14%) for at least a year during follow up, but only 2 patients recovered normal mental function. Our results emphasize the importance of recognizing and treating the multiple illnesses that contribute to dementia in elderly adults. The distribution of illnesses in demented elderly outpatients is different from that reported in younger patients with dementia. Diagnostic strategies and expectations need to be based on data obtained from studies of elderly patients with suspected dementia. PMID- 4031402 TI - Relevance of personality traits to adjustment in group living situations. AB - The study replicates and extends recent work on personality determinants of adjustment. Personality traits and adjustment criteria were selected for relevance to one type of real-life setting (public housing for the elderly that includes a senior center). Personality traits were measured by observer ratings; criteria, by self-report of respondents and perceptions of them by other residents and staff. In concurrent and longitudinal analyses controlling effects of competence and social status, personality traits accounted for significant and meaningful variance in all criteria, and the salience of particular traits varied across criteria. The results are consistent with earlier studies regarding the importance of extraversion and neuroticism to subjective well-being and suggest that they are relevant also to adjustment as perceived by others. The additional traits of congeniality, culture, and nosiness/gossip were related to both inner and outer adjustment measures in the type of situations studied. PMID- 4031403 TI - A structural integration of the Affect Balance Scale and the Life Satisfaction Index A. AB - This study integrates two popular measures of subjective well-being: the Affect Balance Scale (ABS) and the Life Satisfaction Index A (LSIA). Eight ABS items and seven LSIA items are hypothesized to measure four dimensions including congruence, happiness, positive affect, and negative affect. In addition, a second-order factor identified as subjective well-being is postulated to account for the correlations among these four dimensions. This model is examined empirically by using data from the Harris 1974 National Council on Aging survey, Myths and Realities of Aging in America. The proposed formulation is supported and consistently replicated across four randomly divided subsamples. PMID- 4031404 TI - Memory-skills training, memory complaints, and depression in older adults. AB - This study examined the effectiveness of a self-taught program of memory-skills training for older adults complaining of memory difficulties in an immediate treatment/waiting-list design. Analyses of covariance of measures of memory performance, memory evaluation (complaints), and a self-rating depression scale revealed a significant impact of training on memory performance but not on memory complaints or symptoms of depression. Subsequent evaluation of the waiting-list group, which was provided training after participation in the initial portion of the study, provided a partial replication of the design. The pattern of results was remarkably consistent with that obtained in the controlled evaluation of the training program. Finally, those complaining of memory problems were compared with a group of noncomplaining older adults. The two groups were comparable in memory performance and depression scores. Thus, memory complaints do not appear to reflect, systematically, memory problems or depression. PMID- 4031405 TI - Health practices and illness cognition in young, middle aged, and elderly adults. AB - The present paper examines reported frequencies of 21 health practices, beliefs that these health practices can prevent six different illnesses, and beliefs about those illnesses in a community sample of 396 people: 173 young (20 to 39 years), 111 middle-aged (40 to 59 years), and 112 elderly adults (60 to 89 years). Elderly respondents report higher frequencies of health-promoting actions (e.g., regular medical check-ups, avoidance of salt, regular sleep, and eating a balanced diet) than younger respondents. Health practices aimed at reinterpreting stress and controlling emotions (e.g., avoiding emotional stress, staying mentally alert and active) also increased with age. Belief that these 21 practices prevent specific illnesses was consistent across the three age groups. Beliefs about the six illnesses were consistent across age with three exceptions: Elderly people considered themselves more vulnerable to disease, saw it as more serious for them, and were less likely to use chronic mild symptoms, like weakness and aches, as illness warnings. PMID- 4031406 TI - Speed of processing in normal aging: effects of speech rate, linguistic structure, and processing time. AB - Young and elderly adults heard three types of speech materials varying in both length and degree of semantic and syntactic constraints. Time compression was used to vary speech rates systematically to test a speed of processing hypothesis as one explanation of performance deficits associated with normal aging. In addition to segment length effects, the elderly participants showed significantly steeper rates of performance decline with increasing speech rate, with slope constants dependent on the structural constraints of the speech materials. The results are discussed in terms of processing rate hypotheses and context utilization. PMID- 4031407 TI - Aging and similarity grouping in visual search. AB - It has been argued that principles of perceptual organization play an important role in the representation of a visual stimulus and that elderly adults may be deficient in perceptual unit formation. The present study examined the extent to which the Gestalt principles of grouping by proximity and similarity predicted the formation of large perceptual units that could affect performance in a visual search task. The verbal reaction time to determine the presence or absence of a target letter in arrays of 1, 5, or 9 elements was determined for young (20 years) and elderly (69 years) adults. Both age groups could take advantage of the organization implied by Gestalt principles in finding a target in the context of a small implied group. The elderly adults, however, were not able to organize a single perceptual unit composed of eight elements. Thus, although the visual search performance of the age groups was similar, the elderly adults did yield evidence of a perceptual organization deficit. PMID- 4031408 TI - Automatic and controlled semantic priming: accuracy, response bias, and aging. AB - Adult age differences in automatic and controlled semantic priming were investigated by varying the probability of valid primes in a lexical decision task. Tachistoscopic parafoveal stimulus presentation was used to assess age differences in accuracy and response bias as well as latency. Both age groups showed the expected findings of benefits without costs under automatic priming and benefits and costs under controlled priming. Errors for young adults were distributed equally among word and nonword stimuli, whereas older adults displayed a strong tendency to commit errors on nonword trials. PMID- 4031409 TI - Aging and delay effects on recognition of words and designs. AB - Based on a model of inter- and intraitem processes in recognition, this study examined age differences in word recognition (emphasizing interitem elaborative rehearsal) and in design recognition (emphasizing intraitem perceptual processes) over delays of 2, 20, and 200 min. Because repeated exposures should increase intraitem integration, targets were repeated from first to second test halves. Young and old adults showed equivalent accuracy in design recognition and equivalent increases from first to second test halves; the predicted lack of intraitem age differences was supported. Young adults, however, were more accurate than old adults in word recognition, supporting the prediction of age differences in interitem processing. The decline across delays was different for words and designs but was parallel for both age groups. Young and old adults also had equivalent decision criteria and decision speeds. PMID- 4031410 TI - Religion, age, life satisfaction, and perceived sources of religiousness: a study of older persons. AB - Eighty-five persons aged 65 to 88 years participated in this interview study of three issues. The present study supported previous findings of a tendency toward increased religiosity in older age. This was tempered, however, by the finding that, although highly religious older persons tended to report an increase in religiousness over the course of their lives, respondents who were low in religiosity tended to report a decrease. These two groups reported that before the age of 20 a relatively small difference in religiosity existed but by old age this difference had become substantial. Second, there was evidence of a low to moderate positive relationship between religiosity and life satisfaction. Finally, mothers were reported to have had the strongest proreligious influence, although both parents were generally perceived to be important influences in religious development. PMID- 4031411 TI - Adolescents' relationships with grandparents: an empirical contribution to conceptual clarification. AB - Findings from research in which a sample of 132 late adolescents completed questionnaires about their relationships with each of their living grandparents are reported. The grandchildren were most likely to describe their relationships with their maternal grandmothers as close and least likely to describe their bonds with the paternal grandparents in this way. Grandchildren's current evaluations of relationships with their grandparents were affected by access to the particular grandparent in childhood and their perceptions of each of their parents' relationships with the specific grandparent. The findings demonstrate empirically the importance for future research of conceptualizing the grandparent grandchild tie as both particularistic and mediated through a biological and an in-law-child. PMID- 4031412 TI - Assessing interviewer effects in a longitudinal study of bereaved elderly adults. AB - In a 2-year study, bereaved elders who were personally interviewed were compared with those who completed a mailed questionnaire on measures of depression, life satisfaction, and five global measures constructed from a series of bereavement related feelings and behaviors. Data were gathered at six separate measurement periods. Multiple analyses of variance with repeated measures revealed no effect due to group assignment. Although significant changes over time were observed on most measures, these changes were statistically independent of whether the respondents were interviewed or not. The presence of interviewers was, however, associated with higher and more consistent completion rates at each measurement period. PMID- 4031413 TI - Survey of sampling techniques in widowhood research, 1973-1983. AB - This study focused on the use and reporting of sampling procedures found in research on widowhood. The population of all empirical studies on widowhood listed in the Psychological Abstracts and the Sociological Abstracts from 1973 through 1983 was examined with regard to the nature of the sampling procedures used. The results suggest a less-than-desirable state of affairs in such research. Thirty-three percent of the studies did not even contain information on the sampling procedures used. Most investigators who did specify the sampling procedure did not acknowledge awareness of the limitations of generalizations of the results in concordance with the sampling procedures used. Such lack of attention to matters of scientific methodology does not bode well for the advancement of knowledge in this area. PMID- 4031414 TI - The Birren hypothesis of generalized slowing of the central nervous system with age. PMID- 4031415 TI - [Reproduction and immune factors in women. Pregnancy, habitual abortion and HLA histocompatibility]. AB - Immune tolerance of the mother towards the fetus, which is like an allograft, may be explained partially by the presence of immunosupressor factors produced by the placenta. The maternal production of antibodies against trophoblastic antigens would seem equally necessary to prevent the fetus being rejected by cytotoxic maternal lymphocytes. Where there is marked histocompatibility between partners the protecting antibodies are absent and that gives rise to repeated abortions. This hypothesis is discussed as well as the rationale of treatments that are aimed at increasing maternal production of protective antibodies in cases of habitual abortion. PMID- 4031416 TI - [Amniotic fibronectin in normal pregnancy and pregnancy with fetal anencephaly]. AB - Fibronectin, which is an important protein in plasma and in surface cells was calculated in amniotic fluid using a laser ray nephelemetric technique. In normal pregnancies (in 72 samples studied) this protein which rises towards the 18th week of amenorrhoea (mean +/- S.D.: 60.8 +/- 16.0 mg/l), decreases steadily to term (mean 14.8 +/- 8.9 mg/l). In fetal anencephaly (10 samples tested) high levels were also found but the difference as compared with normal levels was not significant. This measurement does not therefore constitute an extra way of screening for closure of the neural tube. PMID- 4031417 TI - [Fetal cardiac biometry. Evaluation of the growth of the right and left ventricles using bidimensional echocardiography in normal pregnancies]. AB - Two-dimensional echography makes it possible to study the fetal heart in a routine obstetrical setting. It is easy to see the four cavities of the heart from the long axis. The speed of growth of the internal diameters of the right and left ventricles have been studied at different stages of normal pregnancy. In this way it has been possible to show the morphometric equilibrium between the right and the left side at different stages of the pregnancy by cardiac ventricular biometry. These measurement are the first step in screening for intra uterine cardiac abnormalities. PMID- 4031418 TI - [Asymmetric uterine malformations with menstrual retention. Apropos of a malformation associating atresia of the cervical isthmus and a pseudo-unicornous uterus]. AB - There is now more or less general agreement how to classify and how to work out the development of symmetrical malformations of the female genital tract. On the other hand, asymmetrical malformations, as well as abnormalities of the development of the cervix and the isthmus are only rarely written about in the literature. It has not yet been possible to draw up a system to display the physiopathology and the embryology of these malformations. We here report a rare case of atresia of the cervix and isthmus as well as a pseudo unicornous uterus. This case should take its place as a piece in the embryological puzzle helping to fill in the details which might one day solve this puzzle. PMID- 4031419 TI - [Puerperal urinary tract infections: role of epidural analgesia, a scheme for prevention]. AB - Epidural analgesia often leads to an increase in the number of catheterisations because of the modifications that result in the physiology of the urinary tract. These catheterisations lead to lower urinary tract infections. Our study on 312 patients shows that: under epidural analgesia it is necessary to carry out catheterisation 3.6 times more frequently; urinary tract infections are 2.6 times more frequent under epidural analgesia; the incidence of urinary tract infection multiplies in accordance with the number of catheterisations whether there has been epidural analgesia or not; a single prophylactic dose of 3 g of amoxycillin can avoid three-quarters of these infections. PMID- 4031420 TI - [Characteristics of pregnancies obtained by in vitro fertilization]. AB - 193 patients had 212 cycles induced for in vitro fertilisation between May 1983 and May 1984. 20 pregnancies of which 10 are still in progress were obtained with 6 spontaneous abortions. There were 2 so-called biochemical pregnancies and 3 extra-uterine pregnancies. The figure of 17% pregnancies where embryos were replaced totals less than 10% if one considers those pregnancies that really carry on. The number of extra-uterine pregnancies is disturbing. Finally, 2 multiple pregnancies continued, one of them being a quadruple pregnancy. The authors have made a special study to see the parameters of the conditions under which the pregnancies were obtained and the prognosis for such pregnancies. PMID- 4031421 TI - [Maternal death of obstetrical origin. Medicolegal aspects]. AB - The authors have become interested in maternal mortality. This study has been carried out solely to look at the medico-legal aspect. Increasingly good health is seen as a right and the doctor the dispenser of this service. The rights of the mother (and of the infant) become of increasing importance. The improvement in obstetrical techniques, which are much better known to the public, have made families far more confident of the results of delivery. This is now seen as something without any danger. But delivering a baby still has lots of risks. Because of this, if an accident happens the obstetrician more than any other doctor perhaps can find himself in the courts. To avoid this he has to know very well the causes of maternal mortality in order to avoid them as far as possible. Furthermore, he must not undertake stupid emergency measures often initiated as measures of desperation caused by his emotional involvement for a patient who is approaching death. Finally, the expert should look for all the causes of death so that he does no wrongly blame the doctor for a maternal death. PMID- 4031422 TI - [Epilepsy and teratogenesis]. PMID- 4031424 TI - [Etiologic factors of fetal hypotrophy. Apropos of 600 cases]. AB - The authors have studied 600 cases histories of fetal growth retardation over a period of 11 years from 1970 to 1981. The incidence of growth retardation was 600 cases in 24,906 deliveries from October 1970 to the end of 1981. This gives an incidence of 2.41%. This figure tends to get less progressively, going from 2.5% at the beginning of our study to a little more than 2% in the last years. 1,498 babies were born weighing less than 2,500 g: 600 of them were really true intra uterine growth retardations (40%) and 898 were babies born prematurely with normal weight for their gestational age. 227 of the 600 small for date babies were born before the 38th week of pregnancy (37.8%). Girls represented 55% of the cases of growth retardation. There was no significant difference in the distribution of age groups of the mothers of small for date babies and the control population. 57% of the women were primiparas whereas only 38% were primiparas in the control population. There is a close relationship between primiparity and young maternal age. 80% of mothers who were under 25 years of age were primiparas. The height of the mother, less than 1,50 m, in our study was significantly less than in the control population (11.9% as against 2.5%). 24% of the mothers weighed less than 45 kg as compared with 7.1% in the general population. The weight gain was not significantly different from that in the control population, if it is not taken in account of mothers who had toxaemia of pregnancy. 158 cases out of the 600, which represents 26% of the mothers, had toxaemia of pregnancy and this confirms how important this aetiological factor is in intra-uterine growth retardation. 113 placentas (18.8%) were studied. They showed histological abnormalities such as infarcts (47 cases) and ischaemic necrosis (18 cases). These features are often associated with toxaemia of pregnancy and/or heavy maternal smoking in 58% of cases. There were abnormalities of the umbilical cords. These were variable so that one could not say that any one was an important cause of intra-uterine growth retardation. A single umbilical artery was found in 8 cases (1.33%). We only speak of recurrent fetal growth retardation, excluding cases of toxaemia, when three or more small for date babies have been born without any particular aetiological reason.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 4031423 TI - [The role of gestational factors in the formation of irreversible neurologic handicaps]. AB - A review of the literature shows that intensive neonatal care has reduced the incidence of neurological handicaps in children. Babies born before term and small for date are, however, more exposed to these handicaps. The pregnancy and socio-economical factors which are now known to play a role in the occurrence of prematurity and small-for-date babies bring about acute fetal distress which results in a demand for more intensive care. However, long-term neurological defects also result from these factors. Prospective studies can be used to assign a predictive score for these predisposing factors. The Maternity Hospital in Liege University has been using a score of these factors for more than 10 years to set up "a risk of premature birth coefficient." This could help towards a more scientific prognosis of the neurological state of the infant. PMID- 4031425 TI - [Cytogenic chorionic nodule of the uterus]. AB - The authors report five observations of endometrial stromal nodules. These nodules are composed of cells identical to those of the endometrial stroma. They constitute the benign form of endometrial stromal tumors. From the macroscopic point of view, they present as nodular formations, most often single, well defined, non-fasciculated, whitish or yellowish sometimes cystisized. From the microscopic point of view, these nodules contain areas of plexiform or glandular arrangement with, occasionally, pseudo-rosettes. Small collagenous zones can often be observed. E.S.N. should be distinguished on the one hand from endolymphatic stromal myosis, and on the other hand from sarcoma of the endometrial stroma. Histogenesis of the lesion is also discussed. PMID- 4031426 TI - [Epiphyseal points of the fetal knee. The impact of growth disorders on bone maturation]. AB - The radiological appearance of bone maturity can be used as a criterion for fetal maturity. This examination with limited irradiation to the fetus is an alternative to amniocentesis. The practice of the latter is not without risk. The authors carried out 194 examinations of the contents of the uterus to look at the epiphyses of the knee between the 34th and 40th week of amenorrhoea. The found three groups: 1) those with normal development; 2) those with delayed development and 3) those with more advanced development. They did not find significant correlation between small-for-dates growth and bony maturity. On the other hand, where there was increased growth of the fetus in cases where maternal diabetes was excluded there was demonstrated that bony maturity accelerated with the presence of Beclard's point from the 34th week onwards. With such great variation in the dates of the appearance of points of ossification the presence of epiphyseal points in the knee cannot be taken as a criterion to establish fetal maturity nor the minimum duration of the pregnancy. PMID- 4031427 TI - [Fibromyolipoma of the uterus. Apropos of a case with a review of the medical literature]. AB - A case of uterine fibromyolipoma in a 75 year old woman suffering from an uterine prolapse is reported. The clinical course, the macroscopic and microscopic characteristics are presented and compared with those in the medical literature. The possible histogenesis is discussed. Our case seems to results from metamorphosis of uterine smooth muscle cells in a leiomyoma. PMID- 4031429 TI - [Non-surgically corrected congenital cardiac malformations in pregnant women]. AB - The authors have studied 787 women with cardiac disease out of 78,594 pregnant women between 1971 and 1980. They found 133 women who had congenital heart disease who were delivered in their service, and they compared these with 260 pregnant women who were normal. They used the classification of the Cardiological Society of New York to grade the functional state of the patients. Five pregnancies had to be terminated before the 16th week because of a worsening of the cardiovascular state of the patient. The majority (79%) of the patients delivered vaginally and 21% had caesarean operations. 20.5% babies were born prematurely (p less than 0.005). 13.4% of the infants weighed less than 2,000 g at birth. Perinatal mortality was 62.9 per 1,000. Maternal mortality was 23.6 per 1,000. The authors conclude that these pregnancies are high-risk pregnancies where the prognosis is only favourable if the heart disease is moderate. This becomes worse when there is cardiac decompensation or cyanosis due to heart disease. PMID- 4031430 TI - [Evaluation of the clinical and biologic means of assessing fetal prognosis in pregnancy toxemias. Apropos of 223 cases]. AB - Two hundred and twenty-three cases notes of patients with toxaemia of pregnancy were analysed in order to try to establish the ability to predict through clinical and biological assessments of the mother the prognosis for the fetus. Statistical analysis methods were chosen to work out the classification of the parameters and to lead to an index of severity that could be established by a multifactorial discriminating analysis. This study confirms that there is an inversion in the circadian rhythm of arterial blood pressure, with an increase in the evening and at night. It shows how bad prognostically blood pressure instability is. On the other hand oedema of the legs is of no significance. Contrary to the view that has been held for a long time, an increase in weight is directly proportional to fetal parameters. As far as parameters are concerned as a whole (both clinical and biological) a rise in blood urea is more discriminating at every stage of the illness and precedes an increase in the platelet count, the changes in creatinine clearance and night blood pressure. Maternal changes are better correlated with fetal variability before the 35th week of the pregnancy whereas after that date the prognostic value of these readings is of little importance. PMID- 4031428 TI - [Necrotizing fasciitis following abdominal hysterectomy]. AB - Necrotizing fasciitis is a rare disease with a high mortality and morbidity rate. The authors report the case of a 52 year old woman with necrotizing fasciitis following abdominal hysterectomy. The early diagnosis and the radical surgery saved her life from this serious type of infection. By describing this case, the authors wish to emphasize their opinion that early diagnosis is essential to survival and the most important aspect of management is early aggressive surgical intervention. PMID- 4031431 TI - [O'Gilvie's syndrome in obstetrics. Review of the literature, apropos of a case]. AB - The authors report one case of idiopathic dilatation of the colon (O'Gilvie's syndrome) which was complicated by perforation of the caecum following a caesarean operation. They study the cases associated with pregnancy from 1913 to 1984. They discuss pathogenesis, diagnosis and therapy. They insist on the usefulness of colonoscopy. PMID- 4031432 TI - [Post-coital contraception using a combination of d-norgestrel and ethinyloestradiol]. AB - This study was conducted to assess the efficacy of d-Norgestrel associated with Ethinylestradiol (Neogynon 21) as postcoital contraception and to report on the clinical experience obtained with this type of contraception. 323 women were treated during 72 h. period following unprotected intercourse. All subjects received 0,2 mg Ethinylestradiol and 1 mg d-Norgestrel (Levonorgestrel) in 2 equally divided doses 12 hours apart. - 1 mg Levonorgestrel was observed to be as effective as 2 mg of the racemic Norgestrel. PCC given during the first part of the cycle, shortened the latter in 80% of relevant cases. Nausea occurred in 30.3% of all patients; among these 14.2% also mentioned vomiting. Three pregnancies occurred of which only one could be attributed to method failure. The corrected failure rate is thus estimated at 0.3%. PMID- 4031433 TI - Nurses' perceptions of mental confusion in the elderly: influence of resident and setting characteristics. PMID- 4031434 TI - Medicine use among the rural elderly. PMID- 4031435 TI - Coping with a community stressor: the threat of a hazardous waste facility. PMID- 4031436 TI - Information giving in medical care. PMID- 4031437 TI - Integrated management of urban mosquito vectors of human diseases. PMID- 4031438 TI - Study on the pathogenecity of Bacillus thuringiensis var. israelensis H-14 strain against silkworm, Bombyx mori under laboratory conditions. PMID- 4031440 TI - A preliminary report on some entomological observations in malaria endemic areas of Kamrup district, Assam. PMID- 4031439 TI - Fleas from erstwhile plague endemic areas of south India and their susceptibility to organochlorine insecticides. PMID- 4031441 TI - Experience in using diethylcarbamazine (DEC) in the control of lymphatic filariasis in India. PMID- 4031442 TI - Immunoprophylaxis against kala-azar: effect of immunization with different doses of EH, and HS strains of L. donovani on challenge with the homologous HS and mouse adopted MS strains. PMID- 4031443 TI - Laboratory studies on cowpox virus. PMID- 4031444 TI - A clinico-mycological study of dermatomycoses in Delhi. PMID- 4031445 TI - Sensitivity of antibrucella antibody to 2-mercaptoethanol and heat. PMID- 4031446 TI - Evaluation of pirimiphos methyl WDP for control of malaria in Tirap district of Arunachal Pradesh. A preliminary report. PMID- 4031448 TI - Status of lymphatic filariasis transmission in Srinagar and Baramulla towns- Jammu and Kashmir state. PMID- 4031447 TI - Human diploid cell strain vaccine for post-exposure rabies treatment. PMID- 4031449 TI - Characterization of mitochondrial monoamine oxidase of Ascaridia galli. AB - Oxidative deamination of various biogenic monoamines by Ascaridia galli monoamine oxidase (MAO) was blocked by different mammalian MAO inhibitors, namely, iproniazid, trans-PcP, nialamide and pargyline and the blockade was observed to be time as well as concentration dependent. The binding of inhibitors with chick ascarid MAO was of the irreversible type and the nature of the inhibition was competitive. Pargyline showed lowest I50 (8 microM) and Ki (12 microM) values. Chlorgyline and deprenyl at 100 microM concentration inhibited MAO by about 60 and 40% respectively, indicating the presence of both type A and type B MAO in A. galli. PMID- 4031450 TI - Reaginic and homocytotropic IgG antibodies in Schistosoma mansoni infected Mastomys natalensis: time courses in untreated infections and after chemoprophylactic and chemotherapeutic treatment. AB - Mastomys natalensis were infected percutaneously with 250 cercariae of Schistosoma mansoni and treated effectively with 5 X 50 mg amoscanate/kg body weight 12-16 (I), 28-32 (II), 56-60 (III) and 101-105 days p.i. (IV) respectively. Levels of reaginic antibodies (RAb) and homocytotropic IgG antibodies (GAb) were assessed by passive cutaneous anaphylaxis tests (PCA) and compared with those in infected, untreated animals. In untreated animals RAb were first detected in the 6th week p.i. Maximum titres around 1:80 were reached after 100 days. High levels persisted until the end of the experiment 185 days p.i. RAb did not develop after treatment I. After treatment II only low PCA titres occurred. After treatment III the time course was similar to the controls but levels were reduced. Treatment IV did not interfere with the occurrence of specific RAb. In the case of GAb, independent of any treatment, after a first peak of PCA titres in the 5th week either a negative pattern or only very low titres were found in week 7. In untreated infected Mastomys GAb levels increased thereafter to maximum titres of about 1:80 at day 70. Later than 100 days p.i. relatively constant titres were observed. The second rise of antibody levels did not occur after early treatment. After treatment II only low transient titres developed. Animals treated in the early patency (III) showed reduced PCA titres and were negative at the end of the observation period. Treatment given 101 to 105 days p.i. rather enhanced the development of GAb. PMID- 4031452 TI - Growth and form of the fourth-stage larvae and early adults of Ascaris suum Goeze, 1782 (Nematoda: Ascaridoidea) developing in pigs. AB - The fourth-stage larvae and adults of Ascaris suum were studied as they developed in the pig intestine from 11 to 22 days after infection. This is a period of rapid growth, in which both sexes increase approximately ten-fold in body length. Further examination of females showed the length increase to be positively allometric with respect to body diameter. The genital primordium in early fourth stage is at the same relative position along the length of the body as it is in the newly hatched larva. During development from fourth stage to adulthood the greater growth of the posterior part of the worm causes the relative position of the developing vulva to shift anteriad. PMID- 4031451 TI - The distribution of the infective larvae of sheep gastro-intestinal nematodes in soil and on herbage and the vertical migration of Trichostrongylus vitrinus larvae through the soil. AB - From May 1982 until September 1983 samples of soil and herbage were collected from a paddock grazed from May to October 1982, and for two short periods between May and July 1983, by sheep infected with gastro-intestinal nematodes. Few infective larvae were recovered from the soil although appreciable numbers of larvae were recovered from the herbage. Infective larvae of Trichostrongylus vitrinus in faeces buried in the soil of grass plots, at a depth of 10 cm, each month from April 1982 until March 1983, migrated on to the herbage at all times of the year, few remaining in the soil. The significance of the soil as a reservoir of infective larvae is discussed. PMID- 4031453 TI - Ancylostoma ceylanicum (Looss, 1911) in golden hamsters (Mesocricetus auratus): pathogenicity and humoral immune response to a primary infection. AB - The response of hamsters to Ancylostoma ceylanicum was studied between days 13 and 200 after infection. The infected hamsters showed signs of anaemia, particularly between the 13th and 60th days. A significant loss in body-weight in the infected animals was also observed during this period. Serological studies with agar gel-diffusion, counterimmunoelectrophoresis and indirect haemagglutination tests revealed positive reactions between the 20th and 60th days followed by a negative response in the latent period between the 60th and 200th days of infection, counterimmunoelectrophoresis test remained positive for a period of 150 days in this experimental model. PMID- 4031454 TI - Biosynthetic labelling of the excretory and secretory antigens of Toxocara canis larvae. AB - Toxocara canis larvae were cultured in vitro in medium containing [35S ]methionine for six days. The medium and the larval tissues were analysed for biosynthetically labelled polypeptides by sodium dodecyl sulphate polyacrylamide gel electrophoresis and autoradiography. Immunoprecipitates with positive and negative human antiserum were similarly analysed, using Staphylococcus aureus to absorb immunocomplexes. The larvae secrete biosynthetically labelled polypeptides into the medium, with three major polypeptides of molecular weights between 99 and 110 X 10(3) the major constituents. Both of these react strongly with human IgG in human positive sera. Many polypeptides become labelled in the larval tissue, but only one polypeptide with similar molecular weight to the ES antigens, strongly reacted with human IgG. PMID- 4031455 TI - Bulinus tropicus, a natural intermediate host for Schistosoma margrebowiei in Lochinvar National Park, Zambia. AB - Snails, provisionally identified as Bulinus tropicus, on the basis of chromosome number, egg protein profile, AcP and HBDH enzymes of the digestive gland, and radular morphology, from Lochinvar National Park, Zambia have been demonstrated to transmit Schistosoma margrebowiei naturally. The identification of the unpaired male schistosomes was confirmed by PGM and AcP analyses. The observations confirm earlier epidemiological predictions, and add another species of mollusc to the two, B. forskalii and B. scalaris, known to be natural intermediate hosts of S. margrebowiei. PMID- 4031456 TI - Regulation of toxocariasis in mice selectively reared for high and low immune responses to Nematospiroides dubius. AB - Test mice have been selectively reared for high (H) or low (L) immune responses to Nematospiroides dubius. After secondary infection with N. dubius, the L mice voided ten times as many eggs in their faeces as the H mice, and at necropsy, 71% versus 20% of the inoculum of N. dubius were recovered as adult worms from the L and H mice respectively. Furthermore, N. dubius were more fecund in the L than in H mice. High or low immune responsiveness was not restricted to N. dubius infection in these mice but was also observed during Toxocara canis infection. The migration of T. canis larvae from gut via the liver to skeletal muscle and CNS was inhibited in H versus L mice. Many more larvae were recovered from the livers of H compared with L mice which was indicative of greater immunity in the H mice. The protective immune response in H compared with L mice to both N. dubius and T. canis included pronounced eosinophilia and elevated antiparasite antibody titres. PMID- 4031457 TI - Observations on the gross changes in the secondary lymphoid organs of mice infected with Nematospiroides dubius. AB - Gross changes in the size of the secondary lymphoid organs were studied during infection with the nematode parasite Nematospiroides dubius. In the strong responder NIH strain, the wet weight of the mesenteric lymph nodes (MLN) increased rapidly following infection with 400 larvae to peak on day 28 at approximately three times the resting weight. Enlargement of the spleens was also marked but regression to normal size took place when the MLN had achieved maximum size. In contrast in C57BL/10 mice, a slow responder strain, the enlargement of the MLN following infection was relatively slow, and there was no evidence of the regression of the spleen, once maximum enlargement had been achieved. When adult worms were removed by anthelmintic, the enlarged MLN and spleens returned rapidly to normal size. However, in mice infected with irradiated larvae (25 krad) the MLN stayed enlarged, despite the absence of adult worms but the spleens of these mice returned to normal size fairly rapidly. It was suggested that irradiated worms survive, perhaps as arrested larvae in the intestinal tissue, for a fairly long time, thereby providing a continual stimulus for the MLN. PMID- 4031458 TI - Attempts to manipulate specific responses to induce resistance to Schistosoma mansoni in Kenyan baboons (Papio anubis). AB - Attempts were made to manipulate specific responses of baboons to protect them from infection with Schistosoma mansoni. In Experiment 1, eosinophilia was induced in naive baboons with Trichinella spiralis larvae given intravenously before intraperitoneal injection of globulin fractions from S. mansoni-infected baboon sera and subsequent percutaneous exposure to S. mansoni cercariae. In Experiment 2, baboons with 8- or 32-week-old primary S. mansoni infections received T. spiralis i.v. before an S. mansoni challenge. In experiments 3 to 5 respectively, naive baboons received intramuscularly before challenge: formalin fixed S. mansoni schistosomula, with Bordetella pertussis as an adjuvant; a preparation of S. mansoni adult worm teguments; and a preparation of IgE-immune complexes obtained from S. mansoni-infected rat sera, with Freunds Complete Adjuvant. Minor, but statistically insignificant, protection was obtained in Experiments 2 (32-week infections) and 3, but was far less than that given by intact, irradiated living vaccines. There are signs on the horizon of non-living vaccines protecting rodents against S. mansoni infection and it would be prudent, as with drugs, to test these in primates before proceeding to man. The results of our experiments, though essentially negative, should help the design of any future vaccine trials in primates. PMID- 4031459 TI - Differentiation of Onchocerca gutturosa and O. lienalis microfilariae by analysis of their GPI isoenzymes. PMID- 4031460 TI - Linkage of loci affecting a murine liver protein and arylsulfatase B to chromosome 13. AB - As-1 is the putative structural locus for murine arylsulfatase B, and Lth-1 determines the presence or absence of a 35 000 dalton acidic liver protein. As-1 and Lth-1 were found to be closely linked using recombinant inbred (RI) strains. Both loci were found to have been cotransferred with the pearl (pe) coat color mutation (chromosome 13) in the B6.C3H pe/pe congenic strain. The linkage relationships between pe, Lth-1, and As-1 were further defined in a backcross. On the basis of the RI data, the congenic strain result, and the backcross data, the following genetic distances were estimated: pe--As-1, 7.1 +/- 4.0 cM; As-1--Lth 1, 2.5 +/- 1.0 cM; and pe--Lth-1, less than 6.9 cM. As-1 and Lth-1 are the first biochemically defined loci to be added to the chromosome 13 linkage map. PMID- 4031461 TI - Genetic analysis of crossfostering data with sire and dam records. AB - A method is presented for the analysis of data from crossfostering experiments in which parts of litters are reciprocally interchanged at birth. Observed variances and covariances of differently related individuals are expressed as functions of theoretical causal components of phenotypic variance (additive direct, dominance direct, additive maternal, dominance maternal, direct-maternal covariance, and environmental). Causal components are estimated by weighted least squares analysis of this system of equations, including a ridge-regression procedure to examine consequences of correlation between observed components. Ridge regression suggests that dominance direct genetic variance is generally underestimated, but that narrow-sense heritability estimates are reliable. PMID- 4031463 TI - Congenital quiver, an inherited neurological defect in the chicken. AB - A new neurological defect in the chicken, congenital quiver (CQ), is characterized by a continuous tremor. At hatching, affected chicks show a rapid tremor, while adult expression varies from a slight quiver to pronounced shaking. Genetic analysis showed the defect to be inherited as an autosomal recessive gene (cq) with complete penetrance. Livability of CQ birds is equivalent to that of their normal sibs. Affected females lay eggs and produce chicks; however, males are essentially sterile. Histologically, their testes show considerable cellular disorganization and a marked reduction in spermatogenic elements. Semen quality evaluations showed CQ males to be significantly inferior in respect to semen volume, sperm concentration, initial motility, and percent normal sperm. Histological examination of CQ brains revealed a number of pathological changes, including extensive degeneration of fiber tracts and neurons across the neuroaxis. There also is a diffuse loss of Purkinje cells in the cerebellar cortex with the remaining cell somas becoming extremely eosinophilic. In addition, many of the blood vessels throughout the white matter showed perivascular cuffing. PMID- 4031462 TI - Chromosomal and behavioral studies of Mexican Drosophila. III. Inversion polymorphism of D. pseudoobscura. AB - Four new gene arrangements of chromosome 3 of Drosophila pseudoobscura are reported, as well as an updated phylogenetic sequence of the inversion polymorphism in this species. Evidence that the Tree Line gene arrangement of chromosome 3 was the original form in D. pseudoobscura, and that Central Mexico is the center of distribution of this species is discussed. PMID- 4031464 TI - An inherited agent of mutation with chromosome damage in wild mice. AB - A population of wild mice in Peru was sampled three times over a period of 20 years. Inbreeding from each sample has shown the population to carry an unusually high frequency of visible mutants and nestling lethals. Preliminary evidence of chromosomal damage suggests an inherited tendency to some form of genetic instability. PMID- 4031465 TI - Leukocyte cell populations in hereditary muscular dystrophic chickens. AB - Adult hereditary muscular dystrophic (MD) chickens were compared with normal chickens for properties of the reticuloendothelial and lymphoid systems. Storrs strain MD chickens exhibited elevated levels of blood heterophils with reduced lymphocytes compared with normal Hyline SC strain chickens. Of the lymphocytes, MD chickens possessed a greater incidence of E-rosette forming cells than were present in SC adults. Similarly, MD spleens possessed more adherent cells with a greater incidence of heterophils than were found in SC chickens. This difference also extended to the peritoneal cavity. Recruitment of peritoneal exudate cells into the cavity with Sephadex stimulation led to a greater incidence of heterophils at the expense of macrophages in MD compared with SC chickens. These findings are discussed in light of the recent detection of a specialized adherent suppressor cell population in MD chickens, and with reference to the muscle disease. PMID- 4031466 TI - Argentophilic structures of spermatogenesis in the yellow fever mosquito. AB - Application of the silver-staining technique to air-dried chromosome preparations of the yellow fever mosquito, Aedes aegypti, revealed the following: 1) intensely stained pericentromeric regions in all chromosomes including the Y chromosome in spermatogonia, and during the primary and secondary spermatocytes; 2) the presence of prepachytene that were not reported earlier; 3) a nucleolus organizing region that persisted up to the late pachytene stage; and 4) rod or ring-like centrioles in pachytene and diplotene stages. In addition, varying numbers (1-4) of silver-stained, ring-like structures were observed during spermiogenesis. The exact nature and function of these ring-like structures is not understood. PMID- 4031467 TI - Inheritance of tweed, a modification of merle, in Australian shepherd dogs. AB - An autosomal mutation is responsible for the modification of merle coat color (previously indicated to be due to a transposable DNA element) to the tweed merle pattern in the Australian shepherd dog. The tweed merle pattern consists of color patches that have a greater range in the intensity of the dilute patches and tend to be larger than the patches of nontweed merle. It has no action on nonmerle dogs. The symbol Tw is proposed for this gene. PMID- 4031468 TI - Chi-square and Mendel's experiments: where's the bias? AB - Mendel has been accused of "cooking" his data to meet a particular hypothesis. The earliest time he could have formulated an hypothesis in the course of his experiments was at the end of the second year of experiments 1 and 2. If he knew what to expect as the result of his first two pea-seed experiments, one might expect the chi-square values of subsequent experiments to exhibit a trend toward smaller values. However, when the individual experiments are, each in turn, subjected to a chi-square test, there is no evidence of the expected trend. With few exceptions, the data show no systematic variation in a particular direction. In our view, the suggestion of bias is not supported. PMID- 4031469 TI - Significance of a diploid number of 20 in the peccary Catagonus wagneri. PMID- 4031470 TI - Lysosomal mutations inhibit lipofuscinosis of the spleen in C57BL mice. AB - Beige, bg, and reduced pigmentation, rp, are recessive mutations affecting lysosomal function. Homozygosity for beige prevented lipofuscinosis of the spleen in C57BL mice and its incidence was greatly reduced by homozygosity for rp. Dilute (d) homozygotes, with normal lysosomes, were susceptible to lipofuscinosis even though their melanosomes were more severely affected than those of beige mice. PMID- 4031471 TI - Prolonged apnea in infancy: evaluation and management. PMID- 4031472 TI - Pediatric near-drowning. PMID- 4031473 TI - Giardiasis: a community problem. PMID- 4031474 TI - Alcoholism. A diagnostic and therapeutic challenge. PMID- 4031476 TI - Popliteal artery aneurysm: case report. PMID- 4031475 TI - Limb salvage surgery for severe leg ischemia. PMID- 4031477 TI - Scoring for senior citizens. The Sandock system: safe, sane and supremely satisfying. PMID- 4031478 TI - Alcoholism research: recent developments. PMID- 4031479 TI - Acute renal failure: contemporary management. PMID- 4031480 TI - Blunt chest trauma. An assessment of chest X-ray findings in the diagnosis and exclusion of aortic rupture. PMID- 4031481 TI - Skin diseases: current concepts, therapy. 3. Inflammation. PMID- 4031482 TI - Alternative delivery systems: an update on HMOs. A message from the Executive Director. PMID- 4031483 TI - Medical malpractice--1985. Reflections of a health care provider. PMID- 4031484 TI - Karyometric changes in the development of the medial and lateral preoptic area of the mouse after gonadectomy. AB - A karyometric study of the medial and the lateral preoptic area of the male albino mouse has been carried out with the aid of a Leitz Image Analysis System (ASM). We have measured nuclear sizes of a control group of sixty mice, aged from the 5th to the 190th day of life. Another group of prepuberally castrated male mice, has been studied at the 25th, 35th, 45th, 55th and 85th postnatal day. The medial and the lateral preoptic area show different development patterns in the control group, and differential effects of castration in these zones were observed. The medial preoptic area, which has frequently been related to changes of sex hormone levels, experiments more important and statistically significant variations than the lateral preoptic area. PMID- 4031485 TI - The fine structure of the subthalamic nucleus in the cat. I. Neuronal perikarya. AB - The fine structure of the neurons in the subthalamic nucleus (Sth) of the cat has been studied. On the basis of the following criteria: the size and the shape of the neuronal perikarya, the ultrastructural characteristics of their organelles, the presence and quantity of somatic spines and their afferentation, three categories of neuronal perikarya were discriminated: large, medium and small neurons. The large neurons have a diameter above 18 microns and nucleocytoplasmic ratio above 1:1,8. These neurons are the richest in organelles, possess the most numerous spines, and are most afferented. According to their shape, the large neurons were subdivided in multipolar, fusiform, and irregular types. The medium sized neurons have a mean diameter between 16 and 13 microns and nucleocytoplasmic ratio 1:1,5-1:1,3. Their cytoplasm contains a lesser number of organelles that are more loosely distributed. The medium neurons possess a small number of somatic spines and are less afferented. The small neurons have a mean diameter below 12 microns and their nucleocytoplasmic ratio is below 1:1,2. Their cytoplasm is poor in organelles and they usually lack spines. The small neurons are remarkably oligoafferented. The large neurons constitute approximately 25%, the medium sized - about 50%, and the small neurons - less than 5% of the neuronal population. The remaining neuronal perikarya do not offer reliable electron microscopical criteria that could allow an unequivocal discrimination. PMID- 4031486 TI - Transplantation of dissociated embryonic brain cells in the brain of adult normal rats and rats subjected to hypoxia. AB - 3H-thymidine-labelled dissociated brain cells of rat embryos were implanted in the brain of adult normal and hypoxia-subjected rats. In both cases these cells survived successfully, differentiated into neurons and glial cells and remained viable throughout the whole experimental period (60 days). These cells were able to synthesize DNA and divide. Dissociated cells of rat embryo brains tended to aggregate after transplantation and were present not only as single neurons but also as large neuronal assemblies having the shape of islets and columns. These cells promoted considerable normalization of degenerated rat cortical neurons after hypoxia. PMID- 4031487 TI - Morphological, biochemical and physiological changes in brain nervous tissue of adult intact and hypoxia-subjected rats after transplantation of embryonic nervous tissue. AB - Data of morphological, biochemical and physiological investigations of brain nervous tissue in adult intact and hypoxia-subjected rats after transplantation of rat embryonic nervous tissue are presented. It has been established that transplants survive and develop successfully in the brain of both intact and hypoxia-subjected rats. The Golgi technique reveals that transplanted neurons form dendrites and axons. They also establish afferent and efferent connections with neurons in different brain regions of the recipient, as has been demonstrated by the horseradish peroxidase (HRP) tract tracing technique. Hypoxia induces reversible as well as irreversible dystrophy of host brain neurons, and transplantation of embryonic brain tissue leads to considerable normalization of the state of reversibly dystrophic neurons. Biochemical investigations have revealed that the spectrum of cytoplasmic proteins of neurons and proteins of the whole brain cortex tissue changed after hypoxia are significantly normalized after subsequent transplantation. It should be also pointed out that there is a considerable increase in the number of proteins in certain fractions which is correlated with regeneration of reversibly dystrophic neurons and other cortical cells. Electrophysiological experiments revealed distinct but short-term EEG changes induced by hypoxia. 1-2 days after hypoxia all EEG parameters were back to normal and displayed no changes during the 2-3-month registration period. PMID- 4031488 TI - [Correlation of a neuropsychologic syndrome with computer-tomographically defined focal lesions of the left brain hemisphere]. AB - The intention was to examine critically, which new possibilities, limitations and possible faultiness are to be expected in connexion with applying computerized tomography in the field of brain localization. The examinations concern the correlation of neuropsychological symptoms with focal cerebral lesions. From july 1980 until september 1982 52 persons out of all patients examined in our CT department during this time, were chosen if they had computertomographically defined focal lesions of one brain hemisphere. They were further examined neurologically, neuropsychologically and by psychological tests using a well connected plan. The results of 33 cases with circumscribed lesions of the left hemisphere are presented in details. The classification of psychological syndromes followed the most important features. A simple procedure for lesion mapping of CT informations, described by MAZZOCCHI and VIGNOLO (1978) was used for documentation and proof of inclusion of the cortical speech region in the examined brain lesions. Thus it was possible to compare the different patterns of lesions and to form groups of patients with a certain localization of the lesions. The correlations of these lesions with the neuropsychological findings were examined in each group. A high degree of correlation in the sense of the classic conception of brain localization of neuropsychological syndromes was found. The ideocinetic motor aphasia was confirmed as a frequent, well-defined syndrome in cases with lesions of the left lower parietal lobulus. PMID- 4031489 TI - [Follow-up observation of correlations between computer-tomographically defined cortical lesions and neuropsychologic findings. A pilot study]. AB - In connexion with the valuation of own results of examinations concerning correlations of computer-tomographically defined focal lesions of the left cerebral hemisphere, which were reported in an antecedent paper, possibilities of correlative follow-up studies are indicated by describing a single case. Besides fundamental advantages, which result from this procedure, it is adequate to the necessary consideration of the space of time between the actual beginning of the disease and the computertomographic and neuropsychologic examinations. PMID- 4031490 TI - Fine structure and vascular supply of the median eminence (ME) in Acipenser ruthenus (Chondrostei). AB - The fine structure and vascular supply of the median eminence (ME) was studied in 57 specimens of Acipenser ruthenus (Chondrostei) by means of light microscopy (normal histology, horseradish-peroxidase (HRP), formaldehyde induced fluorescence (FIF), scanning electron microscopy (SEM) and transmission electron microscopy (TEM) as well as by SEM of vascular corrosion casts. Light microscopy revealed that the ME increases in thickness from caudal to rostral with capillaries invading the subependymal layers only at the rostral median eminence (rME). At the middle (mME) and caudal median eminence (cME) capillaries are limited to the ME outer surface. Short term HRP-application (systemically as well as intraventricularly) resulted in reaction product in the intercellular space throughout the ME after a survival time of 2 hours. The ME tanycytes were distinctly marked after 7 days survival. FIF revealed aminergic cerebrospinal fluid (CSF-) contacting neurons; also the apical part of tanycytes showed specific fluorescence. SEM of vascular corrosion casts showed that the arterial supply of the whole ME results from branches of the hypothalamic artery and/or from those arteries supplying the saccus vasculosus. The whole 2-dimensional primary capillary plexus of the ME drains via portal vessels into the adenohypophysis. As demonstrated by SEM, the ME ependymal surface is made up by oligociliated tanycytes, abundant crown cells and intraventricular protrusions of CSF-contacting neurons. Supraependymal cells are lacking, supraependymal fibres are very sparse. TEM revealed the ME tanycytes with long ciliary rootlets. Their basal processes split into numerous delicate branches forming many end-feet, which end at the basal lamina opposite the fenestrated capillaries of the primary plexus. Like tanycytes, also the crown cells possess branching processes which may contribute to the outer glial membrane. CSF-contacting neurons of the type I (with dense core vesicles ranging in diameter from 100-120 nm and of presumed aminergic nature) and type II (with dense core vesicles ranging in diameter from 160-180 nm and of presumed peptidergic nature) were found. Both types are most abundant in the cME. Small astrocytes reveal delicate processes which cover parts of the CSF-contacting neurons and of tanycytes. Another glial cell type is situated near the basal lamina and forms processes parallel the latter. There are few axo-somal and axo-axonal synapses pointing rather to a humoral regulation of the ME with signals from the ME blood vascular bed or from the CSF acting on CSF contacting neurons. PMID- 4031491 TI - Somatodendritic synapses in the central nucleus of colliculus inferior (CI) in the cat. AB - During the ultrastructural investigation of the central nucleus of cat's colliculus inferior (CI) neurons containing synaptic vesicles were encountered. Their perikarya form somatodendritic synapses and occupy presynaptic positions. These neurons were located in the dorsomedial portion of the central nucleus of the CI. On the basis of their electron microscopical appearance and synaptic relationships they might be discriminated as putative interneurons. PMID- 4031492 TI - Human monocyte adherence to cultured vascular endothelium: monoclonal antibody defined mechanisms. AB - We have evaluated the binding of human peripheral blood monocytes to cultured vascular endothelium as an in vitro model of monocyte interaction with the vessel wall. Monocytes were purified (91% +/- 4 SE esterase positive) by elutriation to avoid contact with surfaces before assay. Adherence of 51Cr-labeled monocytes after 45 min (36% +/- 11 SE) was significantly higher than that observed with autologous radiolabeled neutrophils (9% +/- 5 SE) and was greater on monolayers of human umbilical vein endothelium than on bovine aortic endothelium. Peripheral blood mononuclear cells treated with monoclonal antibody (MoAb) 60.3, a reagent that binds leukocyte membrane complex CDw18, implicated in multiple adherence dependent functions, failed to adhere and flatten on artificial surfaces. Mononuclear cells treated with MoAb 60.3 simulated cells from a patient with recurrent infections whose phagocytes failed to react with MoAb 60.3 and failed to emigrate to extravascular sites in vivo. Incubation of monocytes with MoAb 60.3 inhibited (by 32 to 61%) monocyte adherence to endothelium in a dose dependent manner for periods up to 24 hr, but had negligible effects on basal (unstimulated) neutrophil adherence. Basal monocyte adherence in the presence of MoAb 60.3 remained significantly greater than basal neutrophil adherence. Augmentation of phagocyte adherence to endothelial monolayers by autologous plasma or phorbol ester (PMA) was abrogated by incubation with MoAb 60.3. Studies with immunofluorescence flow cytometry indicated that PMA stimulation of monocytes resulted in a specific 40% increase in monocyte surface expression of the epitope recognized by MoAb 60.3. These in vitro findings, in conjunction with observations from two patients, support the hypothesis that monocyte adherence to endothelium and emigration to tissues is mediated by mechanisms both dependent upon and independent of the CDw18 complex and the epitope recognized by MoAb 60.3. PMID- 4031493 TI - Competition between antigen and anti-idiotypes for rheumatoid factors. AB - Many idiotypic determinants on antibody molecules are thought to be located at the antigen binding site, and therefore the interaction between idiotype (Id) and anti-idiotype (anti-Id) is expected to be inhibited by the antigen. We describe two IgG and one IgM rheumatoid factors whose interactions with their respective anti-Id could only be partially inhibited by very large amounts of antigen, i.e., normal IgG. The anti-Id, however, readily inhibited the binding of their respective rheumatoid factors to IgG. The differences in interaction energies resulted in failure of antigen to readily block the Id-anti-Id interaction, and did not mean that the Id was not at the antigen combining site. The association constants for the Id-anti-Id interactions varied from 1.3 to 14.8 X 10(7) M-1, whereas the strength of the rheumatoid factor antigen bond is on the order of 10(5) M-1 for interaction with monomeric IgG. In addition, the anti-Id were able to remove rheumatoid factors that were bound to solid phase IgG, indicating that anti-Id have the potential for disrupting the immune complexes formed by antigen and antibody. PMID- 4031494 TI - Cutaneous mast cell depletion results from topical corticosteroid usage. AB - The effect of long-term topical application of corticosteroids on human cutaneous mast cells was examined. Two potent corticosteroids, clobetasol-17-propionate and fluocinonide, produced a greater than 85% decrease in histamine content over a 6 wk treatment period, whereas betamethasone valerate, a less potent corticosteroid, produced a 66% decrease. Electron microscopic examination of the biopsies taken from sites after 6 wk of treatment indicate that the reduced levels of histamine were caused by the depletion of mast cells, as evidenced by: the inability to identify any cells representative of mast cells by detailed electron microscopy of the biopsies; and the marked acellularity around the vasculature where mast cells are certain to be detected. Histamine levels did not begin to decline until after 3 wk of corticosteroid treatment, indicating that corticosteroids are not immediately harmful to mast cells. Electron microscopic examination of biopsies taken at the beginning of treatment and 1 wk later showed normal-appearing mast cells, whereas at 3 wk, a small population of mast cells was detected with features usually associated with degenerating or dying cells. These observations suggest that protracted application of corticosteroids to skin is toxic to mast cells. After discontinuation of treatment, the drug-related atrophy associated with chronic application of potent corticosteroids to skin is rapidly reversed, and skin structure returns to near normal by 14 days. Over this time period, however, histamine levels did not increase and mature mast cells could not be observed by electron microscopy. At 14 days post-steroid treatment, the first signs of cells containing sparse amounts of granules having the characteristics of mast cell granules were seen. We interpret this to represent new mast cells beginning to mature in the skin. By 3 mo, histamine levels returned to normal, demonstrating the reversibility of the steroid-induced mast cell depletion. The studies presented here establish the deleterious effects of long-term topical corticosteroid treatment on cutaneous mast cells, and begin to establish a system in which the development of mast cells in tissue can be investigated. PMID- 4031495 TI - Modulation of c-myb transcription in autoimmune disease by cyclophosphamide. AB - This study explores the relationship between autoimmunity and the myb proto oncogene, a gene important for T cell development. The lpr/lpr mice had very large amounts of myb RNA in the lymph node (LN) cells; but unexpectedly, they had abnormally low levels of myb RNA in the thymus, an organ normally rich in myb RNA. Mice with the gld/gld genotype had high myb RNA levels in peripheral LN, similar to lpr/lpr mice, but had normal thymic myb RNA levels. Both lpr/lpr and gld/gld mice and an AILD patient with lymphadenopathy and high myb RNA in peripheral blood cells were treated with cyclophosphamide (CY). In all cases, the CY eliminated the lymphadenopathy and corrected the abnormal myb expression. However, there were significant differences in the clinical and cellular responses to this drug. A single large dose of CY led to marked regression of the lymphadenopathy of gld/gld mice and long-term amelioration of their autoimmune syndrome. In contrast, similar treatment of lpr/lpr mice failed to alter either the lymphadenopathy or the disease process. Consistent with these clinical findings, LN myb was normalized in gld/gld mice by a single injection of CY, whereas there was no effect on myb expression in lpr/lpr mice. The AILD patient reacted much like the gld/gld mice in that myb RNA levels in the peripheral blood, and bone marrow returned to normal after only three doses of CY. The lymphadenopathy and high levels of LN myb mRNA of the lpr/lpr mice could be normalized; this occurred only after long-term treatment with CY. These events were accompanied by an increase in thymic myb mRNA from low levels. These studies have combined a molecular probe with CY therapy to provide insights into the cellular bases for lymphoproliferative autoimmune diseases. PMID- 4031496 TI - Protein G: a powerful tool for binding and detection of monoclonal and polyclonal antibodies. AB - Protein G is an immunoglobulin (IgG)-binding bacterial cell wall protein recently isolated from group G streptococci. We have investigated the avidity of protein G for various monoclonal and polyclonal Ig of the IgG class, and compared it with the binding properties of protein A, the staphylococcal Fc-binding protein. Radiolabeled Ig were mixed with Sepharose-coupled protein G or protein A, and the amounts of radioactivity bound to the matrix-coupled bacterial proteins were determined. The avidity was found to be greater for protein G than for protein A for all examined Ig. Protein G bound all tested monoclonal IgG from mouse IgG1, IgG2a, and IgG3, and rat IgG2a, IgG2b, and IgG2c. In addition, polyclonal IgG from man, cow, rabbit, goat, rat, and mouse bound to protein G, whereas chicken IgG did not. The binding property of protein G was additionally exploited in the Western blot assay, in which iodine-labeled protein G was used successfully for the detection of a rat monoclonal antibody against ovalbumin, and for the detection of rabbit and goat polyclonal whole antisera against human urinary proteins. In these experimental situations, protein G was found to be a powerful reagent for the detection of IgG, and consequently the antigen against which these antibodies are directed. PMID- 4031497 TI - Antibody-independent activation of C1, the first component of complement, by cardiolipin. AB - Lipid vesicles containing phospholipids known to be present in substantial amounts in mitochondrial membranes were tested for their capacity to activate C1. Among them, only cardiolipin (CL) was highly efficient in C1 activation; no such effect was observed with phosphatidylcholine, phosphatidylethanolamine, or phosphatidylinositol. CL was shown to bind specifically C1q, because only unlabeled C1q competed with 125I-C1q for binding to CL. The requirement for C1q was confirmed by the finding that only fully reconstituted macromolecular C1, containing C1q, was activated by CL. The specificity of CL-induced activation of C1 was also demonstrated by introducing adriamycin, an agent known to interact with CL. Whereas adriamycin did not decrease C1 activation induced by immune complexes, it abrogated C1 activation by CL. The latter was shown to be a strong nonimmune activator of C1, because C1-INH did not inhibit CL-induced activation. When the concentration of CL in vesicles was decreased in the presence of phosphatidylcholine, C1 activation was detected only above a critical level of 35 mol% CL, compatible with a minimal density or clustering of CL molecules in the plane of the membrane. Moreover, C1 activation by CL was modulated by the addition of cholesterol. The threshold of CL required for C1 activation was lowered by the incorporation of more than 35 mol% cholesterol into the vesicles. These results show that CL incorporated into liposomes can be a potent nonimmune activator of C1. The negatively charged phosphate groups in CL are likely candidates for Clq-binding. PMID- 4031499 TI - Production of the lymphokine soluble immune response suppressor (SIRS) during chronic experimental schistosomiasis mansoni. AB - Chronic schistosomiasis mansoni is a helminthic infection characterized by cell mediated anti-egg granulomatous reactions and a variety of associated immunoregulatory phenomena. Soluble immune response suppressor (SIRS) is a lymphokine produced by activated suppressor T lymphocytes in various experimental settings. This report demonstrates the presence of SIRS in the sera of mice with chronic schistosomiasis mansoni (at least 20 wk of infection), but not in the sera of mice with earlier infections. Also, cultures of isolated, intact, hepatic, egg-focused granulomas from chronically infected mice released detectable levels of SIRS. These are the immunomodulated lesions characteristic of this infection. Large, intense, unmodulated granulomas obtained from acutely infected mice did not release SIRS. There is, therefore, a strong association between the presence of SIRS in the serum, the production of SIRS by intact lesions, and the chronic, immunomodulated stage of schistosomiasis mansoni. PMID- 4031498 TI - The role of glutathione in lymphocyte activation. I. Comparison of inhibitory effects of buthionine sulfoximine and 2-cyclohexene-1-one by nuclear size transformation. AB - The role of glutathione (GSH) in lectin-induced lymphocyte activation can be studied by quantitating lectin-induced nuclear size transformation in the presence of variable degrees of GSH depletion. Buthionine sulfoximine (BSO) inhibits intracellular GSH synthesis by inhibition of the enzyme gamma-glutamyl cysteine synthetase. By combining endogenous GSH depletion in cell cultures with BSO-induced inhibition of GSH synthesis, lectin-induced lymphocyte activation can be studied at various concentrations of soluble intracellular GSH. With this approach, the percentage of lymphocytes undergoing a nuclear size transformation is minimally affected despite depletion of soluble intracellular GSH to 0.27 nmol/10(7) cells (PBL), which represents approximately 95% depletion of intracellular GSH. When soluble intracellular GSH is depleted to undetectable levels (less than 0.10 nmol/10(7) cells) there is a 10 to 12% reduction in the number of cell nuclei transformed. However, in all BSO-pretreated cultures the lectin-induced nuclear size transformation is intermediate between resting and blast-transformed lymphocytes, suggesting only partial (or aborted) activation. The partial activation response observed in BSO-pretreated cultures may be due to mobilization of the protein-bound pool of GSH, which is relatively resistant to depletion by BSO. That the inhibition of full blast transformation is truly due to GSH depletion was proven by experiments in which GSH was repleted exogenously and a full blast transformation was restored. The results of previous work in our laboratory had shown that the sulfhydryl-reactive agent 2-cyclohexene-1-one (2 CHX) was a potent inhibitor of activation at soluble intracellular GSH concentrations well above 0.27 nmol/10(7) PBL. In the present study, the dose dependent inhibition of activation by 2-CHX was confirmed, but it was shown that the degree of inhibition caused by 2-CHX could be at least partially dissociated from the level of intracellular GSH present at the time of lectin addition and that the inhibitory potential of 2-CHX exceeded that of BSO at comparable levels of soluble intracellular GSH. Thus, the inhibitory properties of 2-CHX cannot be accounted for solely on the basis of GSH depletion. PMID- 4031500 TI - Protective monoclonal antibody against Schistosoma mansoni: antigen isolation, characterization, and suitability for active immunization. AB - Monoclonal antibodies that bind to the surface of developing schistosomula were generated from the spleens of chronically infected mice that were boosted with cercarial glycoproteins. The two most reactive monoclonal antibodies, denoted 152 66-9B and 152-66-1C, were used for identification of surface antigens. The antigen detected by these monoclonal antibodies persisted on the surface of the developing larva for 72 hr posttransformation. This monoclonal antibody effected complement-mediated killing of schistosomula in vitro as efficiently as infected mouse sera. It was also very efficient in inhibiting the infectivity of both cercariae and schistosomula. The antigen reactive with the 152-66-9B monoclonal antibody contains two major polypeptides (45 and 30 KD). These polypeptide chains might have originated from the same protein, because they have the same isoelectric point in two-dimensional gel electrophoresis. Moreover, the affinity purified antigen migrated as only one protein band of approximately 200 KD in SDS PAGE in nonreducing conditions. The 9B antigen was isolated, purified, and used for immunization, resulting in an antigen dose-dependent partial protection against S. mansoni infection. PMID- 4031501 TI - Protection against 17D yellow fever encephalitis in mice by passive transfer of monoclonal antibodies to the nonstructural glycoprotein gp48 and by active immunization with gp48. AB - The protective capacity of antiviral antibodies has generally been considered to depend on their interactions with structural components of the virion. Here we report protection against lethal 17D yellow fever virus (YF) encephalitis of mice by passive administration of nonneutralizing monoclonal antibodies to a 17D YF specified nonstructural glycoprotein, gp48, and by active immunization with purified gp48. Among five anti-gp48 monoclonal antibodies tested, two with high titer complement-fixing (CF) activity were protective, whereas three antibodies with little or no CF activity were not. The ability of antibodies to protect correlated with their ability to promote complement-mediated cytolysis (CMC) of 51Cr-labeled 17D YF-infected mouse neuroblastoma (Neuro 2a) cells. Purified gp48, prepared from lysates of 17D YF-infected Vero cells by immunoaffinity chromatography, was shown to bear both YF type-specific and flavivirus group reactive determinants in a solid phase radioimmunoassay. Immunization of mice with purified gp48 resulted in solid protection in the absence of detectable anti virion antibody, measured by neutralization and radioimmunoprecipitation assays. The results are consistent with plasma membrane expression of gp48 and susceptibility of 17D YF-infected neural cells to CMC, a possible mechanism of host defense in 17D YF encephalitis. Protection provided by immunization with gp48, which bears a group-reactive determinant and is highly conserved among flaviviruses, may have implications in regard to flavivirus vaccine design. PMID- 4031502 TI - A rapid and sensitive method allowing photometric determination of erythrophagocytosis by mononuclear phagocytes. AB - A spectrometric assay for assessing erythrophagocytosis by mononuclear phagocytes is described. It is based on the haemoglobin-catalyzed conversion of a benzidine derivative into a coloured product in the presence of H2O2 (pseudoperoxidase activity). The assay is set up in microtitre plates, and following an uptake phase and removal of non-ingested erythrocytes, pseudoperoxidase activity is measured in detergent lysates of phagocytes, using an ELISA reader photometer. Various detergents and substrates were evaluated. SDS was found to be the most suitable detergent. Diaminobenzidine (in PBS, pH 7.4) was the substrate of choice for enumerating ingested erythrocytes in a range from 10(4) to 5-8X10(5) sheep erythrocytes. Ortho-tolidine (in acetate buffer, pH 5.5) could be used in a range from 2X10(3) to 2X10(5) sheep erythrocytes. The results obtained with human peripheral blood monocytes or monocyte-derived macrophages and IgG-sensitized sheep erythrocytes correlated well with those obtained using 51Cr-labelled, IgG sensitized erythrocytes. PMID- 4031503 TI - Soluble IgG aggregates produced by heating remain stable on freeze-drying. AB - IgG aggregates produced by heating gamma globulin solutions were freeze-dried, kept at 4 degrees C and reconstituted up to 4 months later. By comparison with frozen (-20 degrees C) preparations, only minimal changes in biological reactivity and in physical integrity occurred during this period. These results demonstrate that freeze-dried preparations of heat-aggregated IgG are potentially useful as a reference reagent for the comparative evaluation and standardisation of immune complex assays. PMID- 4031504 TI - Blotting methods applied to investigations of the mitogenic activity of phytohaemagglutinin (PHA). AB - PHA polypeptides were separated by SDS-polyacrylamide gel electrophoresis and transferred to nitrocellulose filters which were then cut into identical discs and used to perform blastogenic stimulation on cultured human peripheral blood lymphocytes. This method offers the following advantages: the high resolution of SDS-polyacrylamide gel electrophoresis, the sensitive immunochemical identification of the polypeptides involved in the mitogenic responses of lymphocytes, the determination in the same experiment of the molecular weight, antigenicity and biological activities of the proteins. PMID- 4031505 TI - A simple microplate assay for the determination of cellular protein. AB - In assays of leukocyte function it is desirable to correlate a specific measurement, e.g., the release of enzymes, the production of metabolites or the secretion of cytokines with the amount of cellular material. Many authors use either the protein or the DNA content of the cells as a reference. Specific measurements of cellular activity are often expressed as a ratio of activity/protein or activity/DNA. This communication describes a dye-binding assay which allows the determination of total protein of the same cell sample which was first used for the quantitation of a specific cellular function. The microplate assay described is an adaptation of the Coomassie blue dye-binding assay without the need of a separate step to lyse the cells. The test is useful for both adherent and non-adherent cells and has a detection limit of less than 500 ng BSA or 5000 leukocytes. PMID- 4031506 TI - A sensitive assay of cytotoxicity applicable to mixed cell populations. AB - The fluorescent vital dye, Hoechst 33342, was used to stain cultured cells prior to assay of antibody dependent complement mediated cytotoxicity. The fluorescence of nonviable dye stained cells is quenched by cellular uptake of trypan blue, but trypan blue excluding cells remain intensely fluorescent. Detection by fluorescence microscopy of one viable prestained cell per 10(5) unstained cells was accurate and reliable. The technique was found to have sensitivity equal to a clonogenic assay for measuring cytotoxicity. The dye stained cell assay may be used to measure depletion of a selected cell type, when those cells are stained prior to mixing with another cell population. This technique may prove useful to study model systems for depletion of tumor cells or T-cells from bone marrow. PMID- 4031507 TI - Use of whole Streptococcus pneumoniae cells as a solid phase sorbent for C reactive protein measurement by ELISA. AB - Monolayers of pneumococcus (serotype 27) on flat bottom polystyrene microtiter plates were used as a solid phase sorbent for the determination of C-reactive protein (CRP) by ELISA. After binding to the monolayer, CRP was quantified with peroxidase conjugated rabbit anti-human CRP immunoglobulin. The method is sensitive (5 micrograms/ml), rapid (less than 2 h) and correlates well with a laser nephelometric assay (r = 0.95, P less than 0.001), and with a classical sandwich ELISA (r = 0.95, P less than 0.001). PMID- 4031508 TI - Miconazole influence on both cellular immune response and hepatic drug metabolism in mice. AB - Miconazole was found to exert a biphasic influence on both cellular immune response and hepatic drug metabolism in adult Swiss mice. Indeed, at the dose of 2.5 or 12.5 mg/kg/twice daily via intraperitoneal route, miconazole depressed delayed-type hypersensitivity (DTH) to sheep red blood cells and hepatic drug metabolism as determined from barbiturate sleeping time, following one-day treatment. By contrast, at the same dose level, miconazole enhanced DTH and hepatic drug metabolism after a five-day administration schedule. Primary humoral response and colloidal carbon clearance were not affected. Although the underlying mechanism remains to be fully elucidated, these findings clearly suggest a close relation between modulation of the cellular immune response and activity of liver drug metabolizing enzymes. PMID- 4031509 TI - The influence on the formation of unstable haemoglobin by the immunomodulating 2 cyanaziridines azimexone and BM 41.332 in mice. AB - Azimexone causes in mice the formation of unstable haemoglobins after a single dose of 20 mg/kg. BM 41.332, another immunomodulating drug of the 2-cyanaziridine class, induces these unstable haemoglobins only after a single oral administration of 500 mg/kg. Subsequently to the formation of unstable haemoglobins we observed a development of Heinz bodies. These effects of the 2 cyanaziridines were elicited neither by methaemoglobin formation nor by an impairment of the components protecting haemoglobin against oxidation (G6PD, catalase, glutathione). The elimination of the altered haemoglobin in the spleen could be followed by measurement of the rise in the iron content of the spleen. PMID- 4031511 TI - Quills, ballpoints, and now computers. PMID- 4031510 TI - The effect of methotrexate on in vitro immunoglobulin production. AB - The effect of Methotrexate (MTX) on pokeweed mitogen (PWM) induced immunoglobulin (Ig) production in vitro was studied over a range of 10(-4) - 10(-12)M MTX, using an enzyme-linked-immunosorbent assay (ELISA). MTX, at a concentration of 5 X 10( 9)M profoundly decreased all classes of Ig production, IgM greater than IgG greater than IgA. Plasma cell numbers, identified using polyclonal antihuman immunoglobulin, demonstrated a similar sensitivity to MTX. There was a paradoxical increase in IgM and IgG production at 5 X 10(-11)M MTX. Clinical implications of these findings are discussed. PMID- 4031512 TI - Aetiology and outcome of severe community-acquired pneumonia. AB - Between January 1972 and December 1981, 50 patients with severe community acquired pneumonia were admitted to the intensive care unit of a district general hospital. A causal pathogen was identified in 41 cases (82%). Streptococcus pneumoniae (16 cases), Legionella pneumophila (15 cases) and Staphylococcus aureus (5 cases) were the commonest. Assisted ventilation was required in 44 patients, of whom 25 died (57%). All 5 patients with staphylococcal pneumonia and 12(75%) with pneumococcal pneumonia died. Only 5 (33%) with Legionnaires' disease died. Mortality was significantly associated with age. Recommendations for the management of severe pneumonia are made. PMID- 4031513 TI - Typhoid fever among Swedish visitors to Kos in 1983. AB - Seven cases of confirmed typhoid fever were discovered among 26 Swedish visitors to the Greek island of Kos in 1983. They had all stayed at the same hotel during the last week of June and the first week of July. During the same period 32 British visitors and 16 visitors from other Scandinavian countries who stayed at the implicated hotel also developed typhoid fever. By analysing questionnaires and by personally interviewing the Swedish visitors, a close association with the eating of salad at dinner on the 4th of July was found. As soon as the first Swedish case was discovered, a carrier among the hotel staff was suspected because it was known that one Swedish and one Finnish case of typhoid fever had been reported in 1981 and 1982 respectively, both patients having stayed at the implicated hotel. PMID- 4031515 TI - Antibiotic advice based on an intra-operative Gram-stain during cholecystectomy. AB - Intra-operative microscopy of the bile was performed during cholecystectomy in 335 patients. Based on the results, individual antibiotic advice was given. Bacteria were seen in the Gram-stained smear from 96 patients of whom 86 had a positive culture. In five patients a negative Gram-stain correlated with a positive culture (sensitivity 94.5%, specificity 95%, positive predictive value 89.5% and negative predictive value 97.5%). In only four patients (1.2%) did the antibiotic advice turn out to be wrong. Eight patients (2.4%) had signs of postoperative infection: one after wrong antibiotic advice, one who did not have prophylaxis because of false negative microscopy, four who did not have prophylaxis for clinical reasons but who had positive Gram-stains, and two despite apparently appropriate antimicrobial prophylaxis. An intra-operative Gram stain as a guide to individual antibiotic advice given by a medical microbiologist during cholecystectomy is recommended. PMID- 4031514 TI - Staphylococcal bacteraemia in Zimbabwe 1983. AB - We have reviewed 107 cases of staphylococcal bacteraemia in order to assess the current clinical spectrum of serious staphylococcal sepsis in Zimbabwe, where staphylococcal bacteraemia is common. Infection was hospital-acquired in 35 cases and community-acquired in 72 cases. The mortality rate was 28%. Most patients were young, with predisposing conditions such as prematurity, protein-caloric malnutrition and measles. The length of the prodromal illness tended to be short and a primary site of infection, usually the lungs or skin, was obvious in 66% of patients. In 30% there was evidence of metastatic spread, usually to meninges, bone, joint and muscle, but endocarditis was uncommon. Metastatic infection was rare when infection was acquired in hospital. Death appeared to be associated with measles, protein-caloric malnutrition, acquisition of infection in hospital, absence of an obvious focus of infection and with inappropriate antibiotic therapy. Aggressive treatment with antibiotics intravenously was the rule. A combination of penicillin and an aminoglycoside was favoured until the nature of the infecting organism was established. Of those patients who died, 38% had received less than 72 h antibiotic therapy. Multiple antibiotic resistance is now widespread in Zimbabwe. PMID- 4031516 TI - Campylobacter fetus peritonitis followed by septicaemia in a patient on continuous ambulatory peritoneal dialysis. AB - A 62-year-old man being treated by continuous ambulatory peritoneal dialysis (CAPD) developed peritonitis due to Campylobacter fetus subspecies fetus (intestinalis), an organism seldom isolated in such circumstances. After appropriate and apparently effective antibiotic therapy, the patient relapsed 6 weeks later with septicaemia. Blood cultures yielded a similar organism, thereby suggesting a clinically silent metastatic infection during the episode of peritonitis, probably at an old arteriovenous fistula. Parenteral tobramycin followed by oral erythromycin achieved a complete cure of this unusual complication. PMID- 4031518 TI - Pneumococcal meningitis in a husband and wife. PMID- 4031517 TI - Spontaneous pseudomembranous colitis not associated with Clostridium difficile. AB - This paper describes two patients who developed macroscopically and microscopically typical pseudomembranous colitis without prior exposure to antimicrobial agents and without detectable Clostridium difficile or its toxin in the faeces. PMID- 4031519 TI - Bacteroides fragilis isolated post mortem from an abscess in a myocardial infarct. AB - An unusual case of an abscess complicating a myocardial infarct is described. Similar cases reported so far are reviewed, with special attention to modes of presentation, possible sources of infection and complications. PMID- 4031520 TI - Biotypes and serotypes of Campylobacter jejuni and Campylobacter coli strains isolated from patients, pigs and chickens in the region of Rotterdam. AB - A comparison was made of the distribution of the bio-and serotypes of Campylobacter jejuni and Campylobacter coli isolated from human patients (205 isolates), intestinal contents of pigs (163 isolates) and intestinal contents and livers of chickens (147 isolates). All strains were isolated in the region of Rotterdam. Campylobacter jejuni biotype 1 accounted for 86%, 1% and 82% of the human, pig and chicken isolates respectively; C. coli was present in 7%, 98% and 14% respectively. Serotyping was possible for 84% of the human isolates, 77% of the pig and 82% of the chicken isolates. Among the human isolates 33 bio-and serotypes were found, of which 22 were similar to those in chickens and only five to those in pigs. Bio-and serotypes from human beings and chickens, ranked in order of decreasing frequency, showed a positive correlation, whereas those from human beings and pigs showed a negative correlation. PMID- 4031521 TI - Failure of erythromycin/rifampicin treatment of legionella pneumonia. PMID- 4031522 TI - Virulence of Toxoplasma gondii. PMID- 4031523 TI - Infections--a new awakening? PMID- 4031524 TI - Coxiella burnetii infection in immunocompromised patients. PMID- 4031525 TI - Ceftriaxone--clinical experience in the treatment of neonates. AB - A group of 104 neonates with clinical signs of infection sufficient to justify treatment with penicillin plus gentamicin received instead monotherapy with ceftriaxone (50 mg/kg once daily). Bacteriological cultures from 20 babies before treatment yielded significant isolates (9 had bacteraemia). Following treatment, infecting bacteria were eradicated from 15/20 babies. Ten of the 104 babies died; all were examined post mortem. Only one death was attributed to bacterial infection. The remaining babies responded well to treatment. No adverse alteration in biochemical or haematological values was associated with ceftriaxone therapy. The incidence of diarrhoea, blood in the stools, necrotising enterocolitis or anti-coagulation problems was the same as in the babies not receiving ceftriaxone. Pharmacokinetic values were determined on 40 babies. Elimination half life (T1/2 beta) and minimum serum concentration (Cmin.) decreased and clearance increased with increasing postnatal age. Postnatal age was the single most significant factor affecting pharmacokinetics. Ceftriaxone is a safe and effective alternative to conventional therapy for infected neonates. Prolonged therapy is associated with superficial colonisation with inherently resistant bacteria. PMID- 4031526 TI - Role of granulocytes and monocytes in the prevention and therapy of experimental Staphylococcus epidermidis endocarditis in rabbits. AB - Rabbits with endocarditis caused by Staphylococcus epidermidis were studied to determine the parts played by granulocytes and monocytes in the prevention or outcome of therapy with cloxacillin. Both monocytes and granulocytes influenced prophylaxis with cloxacillin. The amount of cloxacillin needed to prevent infection in 50% of the rabbits was significantly less in control rabbits than in those selectively depleted of monocytes, as it was also in rabbits selectively depleted of monocytes compared with those that had both granulocytopenia and monocytopenia. Granulocytes strongly potentiated the effect of cloxacillin during prophylaxis, whereas the contribution of monocytes was merely additive. Monocytes also contributed to the effect of therapy with cloxacillin, partially via a cloxacillin-independent mechanism and partially by potentiation of the effect of cloxacillin. Granulocytes did not appear to affect cloxacillin therapy. Results of this study suggest that currently used regimens for prophylaxis and treatment of S. epidermidis endocarditis may need to be adjusted for neutropenic patients. PMID- 4031527 TI - Pneumonia and meningo-encephalitis due to Coxiella burnetii. AB - We describe the case of a 35-year-old man who presented with pneumonia and encephalitis due to Coxiella burnetii. The neurological manifestations of Q fever are discussed and we suggest that C. burnetii be included in the differential diagnosis of patients with pneumonia and encephalitis. PMID- 4031528 TI - A study of the factors influencing tetanus immunity in Israeli male adults. AB - In Israel the immune status of the adult population is largely unknown, because many adults have immigrated from various countries and have no reliable record of immunisation. The Israel Defence Force has implemented a preventive booster immunisation schedule for all its members. The immunity of the adult male population as well as the factors contributing to it were measured and 77.3% found to have sufficient tetanus antibody for protection. The antibody titres in the 3241 subjects studied were found to depend on age. In the older age groups (45-54 years) over one-third had less than 0.01 IU/ml, but even among those of 21 30 years 14% were 'unprotected', if 0.01 IU/ml is taken as the threshold value. Apart from age, the only other contributing factors identified were the occupation as a civilian, education and the number of years since the last immunisation. In our view, the findings call for an immunisation schedule based in each individual country on population serosurveys. PMID- 4031530 TI - Group G streptococcal septicaemia. PMID- 4031529 TI - Pregnant women in contact with rubella. PMID- 4031531 TI - Pneumococcal vaccination. PMID- 4031532 TI - Vaginal disinfectants. PMID- 4031533 TI - Source of Vibrio spp. found in the hemolymph of the blue crab, Callinectes sapidus. PMID- 4031534 TI - Sunlight-induced pathogenesis in systemic lupus erythematosus. PMID- 4031535 TI - Isolation and preliminary biochemical characterization of the human epidermal Langerhans cell. AB - A method is described for the isolation of human epidermal Langerhans cells (LC). Following the disaggregation of the epidermis by gentle trypsinization, the cell suspension is incubated with the fluorescein-conjugated monoclonal antibody OKT6. Using a fluorescence-activated cell sorter, a subpopulation is selected on the basis of positive fluorescence and low forward-scatter, the latter parameter reducing contamination by LC-keratinocyte clusters. The LC averaged 1.7% of the original epidermal preparation. The purity averages 83% as judged either by OKT6 binding or by ATPase activity. Biochemical measurements indicated that the activity of lysosomal enzymes was low with the exception of alpha-mannosidase, which was about 12-fold higher than that of the keratinocyte. The activities of 3 enzymes of intermediary metabolism suggest that the utilization of glucose by the LC is considerably greater than that of the keratinocyte. PMID- 4031536 TI - Experimental photoallergy to systemic drugs. AB - We have induced photoallergy in mice to systemically administered drugs, specifically sulfanilamide and chlorpromazine. Mice were photosensitized to systemic sulfanilamide or chlorpromazine by i.p. administration of drug followed by UVB and UVA irradiation of shaved flank skin, on two consecutive days. Control mice received i.p. drug with no irradiation. In some experiments cyclophosphamide pretreatment, or intradermal Corynebacterium parvum (Propionibacterium acnes), was administered as an immunoadjuvant. All animals were photochallenged on day 5 with i.p. drug followed by UVA irradiation of one ear. Mice that had been previously immunized with drug and UV radiation developed ear swelling and erythema, evident 24 h after photochallenge, but not at 4 h. Control animals showed no reactions. In a typical experiment of photosensitization to systemic sulfanilamide, the experimental group had a mean increase in ear thickness of 6.0 X 10(-2) mm 24 h after photochallenge, while unsensitized control animals showed a mean change of -0.8 X 10(-2) mm. The histopathology of the positive challenge reaction was characteristic of a delayed type hypersensitivity. Adoptive transfer of photoallergy to systemic sulfanilamide to naive recipients was accomplished by i.v. injection of lymph node cells (5 X 10(7) harvested from actively photosensitized donors. Clinical reports have suggested that exposure to systemic medications followed by sunlight can induce an eruption having a photoallergic basis. We now report the first experimental proof of that hypothesis. The murine model should facilitate exploration of photoallergic mechanisms and, in addition, it provides the basis for a prospective test of systemic drugs for their photoallergenicity. PMID- 4031537 TI - Effect of dicarboxylic acids on Harding-Passey and Cloudman S91 melanoma cells in tissue culture. AB - Clinically, dicarboxylic acids have a cytotoxic effect on the abnormally hyperactive and malignant epidermal melanocyte, and diacids from C8 to C13 have been shown to inhibit mitochondrial oxidoreductases. Here, their effect on the growth kinetics and ultrastructure of murine melanoma cells in culture is examined. Cultures of Harding-Passey and Cloudman S91 melanoma cells were exposed to single doses of the disodium salts of C12, C9, and C6 (which does not significantly inhibit mitochondrial enzymes) dicarboxylic acids at concentrations of 10(-3) M to 10(-1) M. With C12 and C9, viability and cell proliferation over 3 days were significantly affected by concentrations greater than 10(-2) M. With exposure to C6 at 10(-1) M and to medium to which NaCl was added to produce equal osmolarity, the effect was much less. Electron microscopy of cells exposed to C9 at 10(-1) M for 1 h and 6 h revealed massive swelling of mitochondria with destruction of cristae, but plasma and nuclear membranes and membranes of endoplasmic reticulum were intact. Similar damage was not seen with C6 at 10(-1) M nor with equiosomolar NaCl. The results confirm (1) the cytotoxicity of dicarboxylic acids for malignant melanocytes, and (2) that the mitochondrion is a prime target for their action. PMID- 4031538 TI - An evaluation of the effectiveness of azelaic acid as a depigmenting and chemotherapeutic agent. AB - In the past five years, it has been reported that certain dicarboxylic acids (C8 C13) and azelaic acid (C9) (AZA), in particular, have a remarkable effect in the management of lentigo maligna, human malignant melanoma, and certain disorders of hyperpigmentation. Preclinical trials, therefore, were undertaken in order to evaluate the effectiveness of AZA as a depigmenting agent and as a chemotherapeutic agent. Twenty-seven uniformly black pigmented guinea pigs were given topical applications of various concentrations (3, 5, 10, 15, and 20%) of AZA preparations for 8 weeks, and their effects on the melanocytes of epilated skin of the backs and the nonepilated ears of guinea pigs were compared to the effects of well-known depigmenting agents. Whereas 4-isopropylcatechol, monobenzylether of hydroquinone, monoethylether of hydroquinone, hydroquinone, and 4-hydroxyanisole were found to be selectively cytotoxic to melanocytes in black-skinned guinea pigs, AZA has little or no visually recognizable effect on melanocytes in these animals. The therapeutic effect of local s.c. injections of various concentrations of AZA preparations on the development of s.c. implanted B 16 melanoma tumor was evaluated in 96 C57BL/6J mice. In addition, 31 BDF1 mice, implanted i.p. with B-16 melanoma tumor, were used to assess the effect of 100 500 mg/kg concentrations of AZA administered i.p. In both studies, AZA revealed no significant tumoristatic or tumoricidal effect on the size, color, and growth of melanoma. The effect of AZA was also evaluated on S-91A (melanotic or pigmented) and S-91B (amelanotic) human melanoma cells in culture. Low concentrations (10(-5) and 10(-3) M) of AZA had no inhibitory effect on the growth of these cells. Only at higher concentrations (greater than 10(-3) M) was a cytotoxic effect on cell viability observed. These observations indicate AZA is not selectively cytotoxic to normal and proliferative melanocytes and has no apparent inhibitory effect on the formative process of melanin pigmentation. PMID- 4031539 TI - Synthesis in vitro of 5,6-dihydroxyindole-2-carboxylic acid by dopachrome conversion factor from Cloudman S91 melanoma cells. AB - The oxidation of dopachrome to melanin occurs spontaneously in vitro but has been shown to be under enzymatic control in vivo. Dopachrome conversion factor, purified from Cloudman S91 melanoma cells, converts dopachrome, which is orange, to a colorless compound. We have purified this colorless compound and identified it as 5,6-dihydroxyindole-2-carboxylic acid. This compound is generated enzymatically from a solution containing dopa and dopachrome and, under these conditions, is not readily oxidized to melanin in solution at pH 6.8. The synthesis in vitro of 5,6-dihydroxyindole-2-carboxylic acid suggests that this compound may be an intermediate in the synthesis of melanin. PMID- 4031540 TI - Glycoprotein metabolism in skin cancer: synthesis, pool size, and partial characterization of glycoproteins in the rat basosquamous cell carcinoma. AB - Uptake of fucose, glucosamine, galactose, and mannose and the incorporation of these sugars into glycoconjugates have been quantified in a model epithelial tumor, the basosquamous cell carcinoma of the rat. Following isolation of glycoprotein and papain digestion, the fucosylated glycopeptides were fractionated according to molecular weight (Mr) and by affinity chromatography. Analysis of cellular material revealed a 2- to 3-fold reduction in the proportion of high-Mr fucopeptides synthesized by the tumor compared with normal epidermis, accompanied by a profound block in the incorporation of galactose into glycoconjugates. Parallel investigation of carbohydrate removed from the cell surface with trypsin or spontaneously shed into the medium indicated a striking decrease in the total release of fucopeptides from the tumor; the Mr was (respectively) normal or increased. Thus the fucopeptide abnormality appears to be accounted for almost entirely by a shift toward accumulation of low-Mr material at internal locations within the cell. PMID- 4031541 TI - Vasoactive intestinal polypeptide (VIP)-like immunoreactivity in the nerves of human axillary sweat glands. AB - The cholinergic innervation of the human axillary sweat glands of hyperhidrotic patients was demonstrated by using the specific Karnovsky-Roots thiocholine method. The cholinergic innervation pattern was compared with the immunohistochemically demonstrated vasoactive intestinal polypeptide (VIP)-like activity at light and electron microscopic levels. The innervation patterns were identical in the light microscopic serial sections. In the electron microscope sections, VIP-like immunoreactivity was localized to the nerve terminals containing large, dense-cored vesicles 100-140 nm in size. No synapses were found, however positively stained nerve terminals were located immediately outside the basement membrane but close to the glandular secretory and myoepithelial cells, blood vessels, and occasionally the mast cells. Our results suggest the coexistence of the two neurotransmitters, acetylcholine and VIP, in the same nerves innervating both eccrine and apocrine sweat glands in human axillae. PMID- 4031542 TI - Ocular findings in patients treated with PUVA. AB - This 5-year prospective study of ophthalmologic findings in 1299 patients treated with oral 8-methoxypsoralen photochemotherapy (PUVA) for psoriasis failed to demonstrate a significant dose-dependent increase in the risk of developing symptomatic cataracts. These patients were instructed to wear UVA-blocking eyeglasses when exposed to sunlight and during treatment for a 12-h period beginning from the time of 8-methoxypsoralen ingestion. However, we did observe a small increase in the risk for development of nuclear sclerosis and posterior subcapsular opacities among patients who received at least 100 PUVA treatments, compared to patients with fewer than 100 treatments (relative risk = 2.3 and 3.0, respectively; p less than .05 both comparisons). We compared our results to those of a large, population-based study and found, after adjusting for differences in methods, that the prevalence of cataracts in our study patients, aged 52-75 years, was not significantly different. Since the latency period for development of symptomatic ocular abnormalities may be longer than 5 years, continued surveillance of our cohort and continued use of appropriate ocular protection by all patients treated with PUVA is indicated. PMID- 4031543 TI - A mild form of xeroderma pigmentosum assigned to complementation group G and its repair heterogeneity. AB - The specific heterodikaryon complementation results allowed us to allocate a 37 year-old female patient with xeroderma pigmentosum (XP31KO) to complementation group G of rare incidence. A mild form of XP31KO as the third group G patient manifested normal skin reaction to phototest, no physical or neuromental abnormalities, and a basal cell epithelioma, in contrast to the reference group G XP2BI. XP31KO cells showed 25% unscheduled DNA synthesis (UDS) after 10 J/m2 UV compared to less than 5% UDS in XP2BI cells and less hypersensitive responses to UV radiation and 4-nitroquinoline-1-oxide killings than did XP2BI cells. Such a repair phenotype of XP31KO presents an intragroup-G heterogeneity. PMID- 4031544 TI - A new serological assay for Staphylococcus aureus infections: detection of IgG antibodies to S. aureus lipase with an enzyme-linked immunosorbent assay. AB - Purified Staphylococcus aureus lipase was used as antigen in an enzyme-linked immunosorbent assay (ELISA) that detected IgG antibodies in 169 patients with infections due to S. aureus, in 122 patients with infections not due to S. aureus, and in 167 healthy controls. Eighty-eight percent (21 of 24) of the patients with endocarditis due to S. aureus showed a positive level of antibody to lipase or a significant change in antibody titer during the first month, as did 89% (17 of 19) and 28% (5 of 18) of the patients with complicated and uncomplicated septicemia due to S. aureus, respectively. The specificity for S. aureus infections was high; only one patient in the non-S. aureus endocarditis and septicemia groups showed a significant rise in antibody titer, and this rise did not reach a positive antibody level. Patients with recurrent furunculosis or chronic osteomyelitis due to S. aureus responded in only 15% and 23% of cases, respectively. We suggest that the antibody-to-lipase ELISA could be used as a valuable complement to other serological assays in diagnosing serious S. aureus infections because of its high sensitivity and specificity. PMID- 4031545 TI - Detection of fever with infrared thermometry: a feasibility study. AB - Fever is a remarkably sensitive indicator of infectious disease. The thermometer in clinical use today is basically that developed over a century ago, measuring heat conducted from skin or mucous membranes to an adjacent probe. In dealing with immunosuppressed granulocytopenic patients, the need was realized for an instrument by which temperature might be determined without a probe contact. Infrared pyrometers have been used in industry to record the temperature of mechanical objects at a distance. We tested the feasibility of using such an instrument to detect fever in humans. In a controlled and blinded fashion, infrared measurements from the eyes, axillae, and areas below the ear lobes (E spot) of 140 febrile and afebrile patients were compared with rectal temperatures recorded by a standard thermometer. The eye and E spot provided the most accurate readings. Infrared measurements of the right eye identified 57 (95%) of 60 febrile and 72 (90%) of 80 afebrile patients correctly. Overall, 92% of all patients were correctly categorized by use of the infrared thermometer at this site. We conclude that this approach is feasible and, with further technical developments, may be applicable for routine clinical use. PMID- 4031546 TI - Acute myocardial effects of chloramphenicol in newborn pigs: a possible insight into the gray baby syndrome. AB - Mechanical function and mitochondrial respiration were observed in newborn pig hearts in the presence of chloramphenicol. Isolated perfused hearts exposed to chloramphenicol (25, 50, or 100 micrograms/ml) demonstrated acute reductions in pressure development and cardiac output accompanied by elevated left atrial filling pressure. The effects of chloramphenicol and chloramphenicol succinate (25, 50, 100, or 200 micrograms/ml) on oxidative activity of isolated mitochondria were also investigated. With unesterified chloramphenicol, inhibition of state 3 respiration was most apparent when glutamate and palmitylcarnitine were supplied as substrates. Inhibition of mitochondrial oxidation of succinate or glutamate was only detectable at 200 micrograms/ml. Inhibition of alpha-ketoglutarate oxidation was not seen at any concentration of antibiotic studied. Chloramphenicol succinate most strongly inhibited state 3 oxidation of succinate and alpha-ketoglutarate and had relatively mild effects on oxidation of glutamate and palmitylcarnitine. Succinate oxidation by submitochondrial particles was unaffected by chloramphenicol succinate, a result suggesting interference with succinate transport. PMID- 4031547 TI - Water-related nosocomial pneumonia caused by Legionella pneumophila serogroups 1 and 10. AB - Between August 1978 and November 1983, 21 cases of pneumonia caused by Legionella pneumophila occurred in the Leiden University Hospital, mainly among immunocompromised patients. A new serogroup of L. pneumophila, designated serogroup 10 (prototype strain Leiden 1), was isolated from bronchial secretions of four patients, and five patients had serological evidence of infection with this organism. Nine patients had a culture-confirmed infection with L. pneumophila serogroup 1. L. pneumophila serogroups 1 and 10 were also isolated from the hot potable water supply in the building to which 19 of the 21 patients had been admitted. The isolates of L. pneumophila serogroup 1 from patients and the hot potable water were identical in studies with monoclonal antibodies and had the same plasmid profiles. These findings provide further evidence that in our hospital potable water contaminated with L. pneumophila is a source of infection, mainly in immunocompromised patients. PMID- 4031548 TI - Vaginal redox potential in bacterial vaginosis (nonspecific vaginitis). AB - To explore of the association of bacterial vaginosis with anaerobic bacterial growth in the vagina, we measured the redox potential (Eh) at the vaginal epithelial surface of women with this syndrome. Among normal women, the value for Eh in the vagina ranged from +322 mV to +137 mV (mean, +170 mV); whereas among women with bacterial vaginosis, the Eh ranged from +71 mV to as low as -257 mV (mean, -92 mV). Following successful treatment of the vaginosis with metronidazole, the vaginal Eh increased to a mean of +208 mV. Thus, the low redox potential in the vagina during bacterial vaginosis appears to be due to microbial metabolism in the vagina and does not represent a persistent host factor responsible for the anaerobic vaginal flora. Any host factors responsible for bacterial vaginosis remain to be elucidated. PMID- 4031549 TI - The effect of placebo and virucidal paper handkerchiefs on viral contamination of the hand and transmission of experimental rhinoviral infection. PMID- 4031550 TI - Defective reticuloendothelial system Fc-receptor function in patients with acquired immunodeficiency syndrome. PMID- 4031551 TI - Serum antibodies to heat-labile enterotoxin of Campylobacter jejuni. PMID- 4031552 TI - A case of melioidosis in West Africa. PMID- 4031553 TI - The role of C5 in experimental murine paracoccidioidomycosis. PMID- 4031554 TI - White blood cell counts in patients with Campylobacter-induced diarrhea and in controls. PMID- 4031555 TI - Serological evidence for simultaneous occurrences of Lyme disease and babesiosis. AB - Babesia microti and Borrelia burgdorferi, the spirochetal agent of Lyme disease, are both transmitted by the tick Ixodes dammini. Serological evidence has shown that 54% of the patients with babesiosis tested have IgG and IgM antibodies to the spirochete causing Lyme disease. Likewise, 66% of randomly selected patients with Lyme disease from geographic areas endemic for both diseases, but not from areas where babesiosis does not occur, also have IgM and IgG antibodies to B. microti. Antigenic cross-reactivity is not the reason for these findings, as laboratory animals experimentally infected with B. microti do not develop antibodies to B. burgdorferi, and laboratory animals immunized with organisms derived from pure cultures of spirochetes do not develop antibodies to B. microti. We suggest that these patients are concurrently exposed to both organisms by doubly infected tick vectors. PMID- 4031556 TI - Interaction between human monocytes and penicillin G in relation to the antibacterial effect on Staphylococcus aureus. AB - The influence of the presence of monocytes on the effect of penicillin G on Staphylococcus aureus was studied. Conditions were varied in such a way that phagocytosis and intracellular killing of S. aureus by monocytes did not occur, was short lasting and limited, or long lasting and extensive. Synergism between penicillin G and monocytes was observed in the absence of and during limited phagocytosis and intracellular killing by the monocytes. When phagocytosis and intracellular killing were optimal, addition or antagonism between penicillin G and monocytes was observed. Enhancement of the antibacterial effect of penicillin G was also obtained in the presence of monocyte supernatant (the cell-free medium in which monocytes had been incubated for 3 hr). This indicates that monocytes secrete a factor that enhances the antibacterial activity of penicillin G. Serum inhibits the activity of this factor. PMID- 4031557 TI - A point-source outbreak of campylobacteriosis associated with consumption of raw milk. AB - After a one-day field trip to a Minnesota farm, 22 (45%) of 49 third-grade students and three (14%) of 21 adult chaperones developed campylobacteriosis. Campylobacter jejuni was isolated from specimens of 13 children and one asymptomatic adult. Illness was associated with the consumption of raw milk during a picnic lunch (odds ratio = 41.0, P less than .0001) and participation in hand milking of cows (odds ratio = 37.5, less than .0001). Two additional findings implicated consumption of raw milk as the vehicle for transmission. First, the odds ratio for illness among those who drank raw milk and did not milk cows was 11.8 (P less than .01), whereas the odds ratio for illness among those who milked cows but did not drink raw milk was only 1.2 (P greater than .02). Second, there was a dose-response relation between the occurrence of illness and the quantity of raw milk consumed (P less than .0001). Neither the median incubation period nor duration of illness was related to the amount of milk consumed. All persons with a stool culture positive for C. jejuni excreted the organism for at least two weeks, but less than six weeks. No secondary cases of illness were documented. PMID- 4031559 TI - Effect of magnesium on production of toxic-shock-syndrome toxin-1 by Staphylococcus aureus. PMID- 4031558 TI - Postpartum rubella immunization: association with development of prolonged arthritis, neurological sequelae, and chronic rubella viremia. AB - Six women developed chronic long-term arthropathy after postpartum immunization against rubella. All individuals developed acute polyarticular arthritis within 12 days to three weeks postimmunization and have had continuing chronic or recurrent arthralgia or arthritis for two to seven years after vaccination. Acute neurological manifestations, consisting of carpal tunnel syndrome or multiple paresthesiae, developed postvaccination in three women. Two have developed continuing active or chronic recurrent episodes of blurred vision, paresthesiae, and painful limb syndromes together with recurrent joint symptoms. Chronic rubella viremia has been detected in peripheral blood mononuclear cell (MNC) populations in five of the six women up to six years after vaccination. In addition rubella virus was isolated from breast milk MNCs in one individual at nine months postvaccination and from peripheral blood MNCs in two of four breast fed infants studied at 12-18 months of age. Immune responses to rubella virus studied at sequential intervals after vaccination correlated with development of rheumatologic and neurological manifestations. PMID- 4031560 TI - Electron microscopy of the bacillus causing cat-scratch disease. PMID- 4031561 TI - Probit analysis of data for infection with echovirus-12 should generate a straight line. PMID- 4031562 TI - Subclinical infections with Boutonneuse fever in western Sicily. PMID- 4031563 TI - Reduced uromucoid excretion in the elderly. PMID- 4031564 TI - [Studies on the alteration of the unconjugated estriol level of the maternal vein after the onset of labor]. AB - We measured maternal venous unconjugated estriol (UE3) levels in 244 cases (218 cases with labor and 26 without labor). We investigated the relationships between several obstetrical factors and UE3 levels. There was no significant difference between the group with labor and the group without labor. However, in multipara, the UE3 level fell gradually with prolonged duration of labor. There were significant positive correlations between the UE3 levels and birth weights (n = 82, r = 0.375, p less than 0.001), and placental weights (n = 82, r = 0.381, p less than 0.001) in multipara with labor. There was no significant difference according to sex between the UE3 levels of a mother carrying a male or female fetus. The UE3 levels of fetal distress cases (n = 30, mean +/- S.E. 20.0 +/- 8.6 ng/ml) were significantly (p less than 0.02) lower than those without fetal distress (n = 188, 24.5 +/- 9.7 ng/ml). These data suggest that after the onset of labor, maternal venous UE3 has some relationship to feto-placental function. PMID- 4031566 TI - [Cytogenetic, morphological and clinical studies on partial hydatidiform moles]. AB - To establish the clinical management of partial moles, cytogenetic, morphological and clinical studies of 57 partial moles, including three twin cases, were performed. The karyotypes of the 54 singletons were 46 triploid and eight diploid. By examining the genetic markers, two of the diploid moles were proved to be derived from normally fertilized conceptuses. Molar tissues from two twin cases had a 46,XX karyotype of androgenetic origin, while the normal placenta and fetus were derived from normal conceptuses. An embryo (or fetus) (26.9%) or only an umbilical cord (9.6%) was found in some triploid and diploid moles. Vessels with erythroblasts were also recognized in most cases. In addition, there was a positive correlation between cyst formation and gestational length in triploid conceptuses. These findings suggest that triploid partial moles are an altered form of missed abortion. The mole became invasive in one twin case with an androgenetic mole, but the remaining cases had uneventful courses. These results indicate that partial moles can be divided into three groups: Triploid, Diploid derived from normally fertilized conceptus, Binovular twins with androgenetic mole, and that, except for those in group 3, partial moles have no malignant potential and require no intensive follow-up. PMID- 4031565 TI - [Studies on the management of CIN accompanied by infertility]. AB - We performed cytological examinations on 863 of the 969 patients (89.3%). In the final diagnosis, 4 patients had carcinoma in situ (0.5%) and 1 patient had microinvasive carcinoma (0.1%). Therefore, it is important to perform cytological examinations on infertility out-patient s, and conduct routine cytological examinations when infertility treatment is being continued over long periods. The detection rate for the 18 patients who required detailed examination did not differ between primary and secondary infertility, or with the period of infertility or the factor causing infertility. The follow up after conization should be done carefully, and the patient should be encouraged to become pregnant as early as possible. Unlike fertile women, in infertile women, conization should be performed, even in the case of carcinoma in situ, provided: There is a specialist well-experienced in cytology, colposcopy, and histology; the patient and family are fully satisfied with the physician's explanation; the physician can maintain good contact with the patient and family and continue to provide adequate follow up treatment, and the lesion is in the ectocervix, and the whole lesion can be removed by conization without leaving intact foci. PMID- 4031567 TI - [Studies on the tocogram with bearing-down efforts during labor--analysis of the waveform and its clinical significance]. AB - Together with a recording of external tocogram (Ex. toc.), intra-uterine pressure (IUP) and pressure between fetus and birth canal (PFB) were measured simultaneously and continuously, in 77 women during labor who were showing uterine contraction (UC) with bearing-down efforts (BDE). UC curves with BDE were analyzed to detect characteristic features and the sequence of their change in the second stage of labor. The following results were obtained. IUP curves were able to be classified into three types (Type A, B and C) according to the characteristics of the BDE waveform. This means of categorization was also able to be applied to the waveforms of PFB and Ex. toc., because those two pressure curves were essentially the same as that of IUP. Most of the type A contractions were observed early in the second stage of labor, and type B and C made their appearance successively. During the period of labor, from the first appearance of BDE on UC until the termination of the delivery, the mean frequency of UC with BDE was estimated to be 43 times in premiparae (Type A 5.8, Type B 19.7 and Type C 15.5 times) and 13 times in multiparae (Type A 2.0, Type B 2.7 and Type C 7.6 times). 3) Clinical significance from the point of view of parameters was as follows. The peak pressure of IUP increased slightly as labor progressed and the mean levels were 14.4kPa in Type A, 17.7kPa in Type B and 23.5kPa in Type C, respectively. PFB peak pressure, however, remained close to 50kPa in all cases irrespective of the type of curve. The mean BDE pressure was about a half the mean peak pressure for IUP and PFB respectively. The ratio of the levels of peak pressure of PFB and IUP (PFB/IUP ratio) were found to be approximately from 2.04 to 3.12. By a power spectrum analysis, the maximum levels of power in Type B curves were found at both 0.01 Hz and 0.2 Hz. The differential calculus curves estimated from IUP with BDE were able to be divided into three types, and the maximum value in Type B curves of IUP was 12.8kPa/sec. The IUP levels were plotted against those of PFB estimated from UC curves and the curve obtained indicated a straight line relationship. The levels of PFB were consistently two or three times higher than those of IUP.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 4031568 TI - [Establishment of a new human endometrial adenocarcinoma cell line, Ishikawa cells, containing estrogen and progesterone receptors]. AB - A new human endometrial adenocarcinoma cell line, Ishikawa cells, was established from an endometrial adenocarcinoma from a 39-year-old woman and has been maintained in vitro for more than 3 years. The cells were found to form a monolayer in a mosaic fashion and to tend to pile up. Population doubling time was calculated to be about 36, 29 and 27 hours at the 9th, 40th and 50th generations, respectively. The modal chromosomal number of the cells fell in a diploid range. Histology of the tumor induced in athymic nude mice showed it to be a well differentiated adenocarcinoma which closely resembled the original human tumor. Estrogen receptor and progesterone receptor were demonstrated to occur not only in the induced tumor in athymic nude mice but also in in vitro culture cells. From the fact that the cell growth was maintained in an estrogen free medium, it appeared that the cells had no estrogen dependency. PMID- 4031569 TI - [Studies on a cell sampling method in mass screening for uterine cervical cancer- comparison of data obtained with a cotton tipped applicator, wooden spatula and cotton tipped applicator plus colposcopy]. AB - In mass screening tests for uterine cancer carried out Shimane Prefecture, we used three different scraping methods. This summary is a report of a comparison of the findings with each method. Results are as follows: From 1973-1982, 214, 798 Japanese women were examined in mass screening tests. Among the 42, 443 examined using a cotton tipped applicator, there were 15 (0.035%) with mild dysplasia, 8 (0.019%) with severe dysplasia, 6 (0.014%) with carcinoma in situ and 8 (0.019%) with invasive carcinoma. In 38,106 women examined using the spatula, 25 (0.066%) had a mild dysplasia, 10 (0.026%) a severe dysplasia, 18 (0.047%) a carcinoma in situ and 26 (0.068%) an invasive carcinoma. In 134,249 examined using a cotton tipped applicator plus colposcopy, 283 (0.211%) had a mild dysplasia 108 (0.080%) a severe dysplasia, 57 (0.042%) a carcinoma in situ and 78 (0.058%) an invasive carcinoma. Thus, the use of a cotton tipped applicator plus colposcopy leads to higher rates of detection of mild and severe dysplasia. In the group with a negative Papanicolaou smear and for whom the cotton tipped applicator plus colposcopy was used, there were 214 with a mild dysplasia, 65 with a severe dysplasia, 11 with a carcinoma in situ and 7 with an invasive carcinoma. The combination of cotton tipped applicator and colposcopy proved to be the most effective for mass screenings for uterine cancer, as the detection rates for severe dysplasia and carcinoma in situ were higher and there were fewer incidences of false negative results. PMID- 4031570 TI - [Studies on hyperthermia and radiation treatment of uterine cancer using multicellular tumor spheroid]. AB - Anticancer effects of hyperthermia and radiation on uterine cancer cells were studied using multicellular tumor spheroids and monolayer cultured cells. Cell lines used were SKG-3a(uterine cervical epidermoid carcinoma), HeLa-S3 (uterine cervical adenocarcinoma) and HEC-59 (uterine corpus adenocarcinoma). All cell lines grown in monolayer culture have similar growth rates, but as spheroids, their growth rate are HeLa-S3 greater than HEC-59 greater than SKG-3a cells. The radiosensitivity of all cell lines in monolayer are as follows according to dose survival relationships. :HEC-59 greater than HeLa-S3 greater than SKG-3a cells. Survival assay to hyperthermia on SKG-3a and HEC-59 cells resulted in no response from 37 degrees to 41 degrees C and in cytotoxicity over 42 degrees C. There is no difference in sensitivity to hyperthermia between the two types of cells. The responses of three cell lines grown as spheroids in hyperthermia and radiation demonstrated that the combination therapy is not effective on the SKG-3a cell, but induced a 1.3-fold effectiveness ratio in HEC-59 and 1.6-fold in HeLa-S3 cells, i.e. more cytotoxicity than with radiation alone. These results suggests that hyperthermia and radiation employed together may be more effective on radioresistant adenocarcinoma cells than on radiosensitive epidermoid carcinoma cells. PMID- 4031571 TI - [Studies on a handheld computer system for perinatal care]. AB - The present paper demonstrates a handheld computer system for use in perinatal care. The features of the system are as follows: The gestational age and fetal body weight were determined by analyzing the data from ultrasonography with the high-order regressive equation. The combined use of the linear regressive equation and Ott's equation was more useful in precisely calculating the fetal abdominal circumference. In order to decrease input error, attempts were made to minimize key-operations for data-entry. The use of the screen edition system also made it easier to correct input error. It was concluded that this system was practical and easy to handle, and would be a useful aid in clinical care. PMID- 4031572 TI - [On the effect of an oocyte factor on the formation of cumulus oophorus in human antral follicles]. AB - The possible existence of a granulosa cell growth factor (GGF) in the oocyte was investigated by using the mitotic index (%) of granulosa cells (GC) in human antral follicles. 50 follicles (0.4-13 mm in diameter) in 35 ovaries obtained from 35 women were used for the experiments. In each follicle, GC were divided into two groups, cumulus and mural GC, according to the distance from the oocyte. The following results were obtained: The Mitotic Index (MI) of cumulus GC was 8.2 +/- 0.5 (M +/- SE) and was two fold higher than that of mural GC, 4.7 +/- 0.4 (p less than 0.001). As follicles developed, MI of mural GC increased until their diameter reached 3mm but beyond 3mm, MI decreased. On the other hand, there was little relationship between MI of cumulus GC and the follicular size, and MI was constantly high in value. MI of both cumulus and mural GC was higher in the late follicular phase than in other phases of the cycle. These results suggest that the proliferation of GC in growing follicle might be regulated by some unknown substance (GGF) secreted from the oocyte as well as the endocrinological environment. It is also suggested that the presence of the oocyte plays a crucial role in the cumulus oophorus formation in the antral follicles. PMID- 4031573 TI - [A study on factors influencing survival in stage I ovarian cancer]. AB - Early diagnosis is difficult in ovarian cancer and the prognosis is unfavorable even in stage I case. A total of 131 cases with stage I ovarian carcinoma were treated at our institution, 73 were stage Ia, 13 were stage Ib, 45 were stage Ic and 39 were LPM. To define the criteria for selection of therapy, we retrospectively reviewed the stage I ovarian cancer. The results were as follows: The best survival rate was demonstrated in 96% of LPM cases followed by 73% of endometrioid adeno-carcinoma. Cases with rupture of capsule and with ascites at surgery influenced the 5 year survival rate. We observed no difference in survival rate between the conservative operation (unilateral salpingo oophorectomy) group and the complete operation (bilateral salpingo-oophorectomy and total hysterectomy) group. Those who had received postoperative chemotherapy showed the longest survival rate of 86%. Evaluation of deaths; 9 of 21 with stage Ic died within 12 months after surgery, and 4 of 7 with stage Iai between 1 and 3 years. The analysis has shown the importance of adequate postoperative treatment and of strict follow-up to guard against recurrence of malignancy in patients with ruptured tumor capsules as well as in those with ascites. PMID- 4031574 TI - [The morphology of sensory corpuscles in the joint capsule--ultrastructural and histochemical study]. AB - Sensory corpuscles in the cat elbow joint were observed by light and electron microscopy. Two types of corpuscles were identified, i.e. Pacini-type and Ruffini type corpuscles. Silver impregnation revealed a single straight axon terminal in Pacini-type and highly-ramified fine axons in Ruffini-type corpuscles. Pacini type corpuscles, 100-200 microns long and 30 microns wide, consisted of dense lamellae of lamellar cells and thick capsule. The lamellar portion contained a centrally-located axon terminal, and was similar in organization to the inner core of the typical Pacini corpuscle. The capsule was the continuation of perineurial sheath. This corpuscle was devoid of outer core structure as seen in a typical Pacini corpuscle. Ruffini-type corpuscles, 50-150 microns long and 25 50 microns wide, had the branched axon terminals with varicosities under the incomplete capsule. Axons, which were surrounded by thin Schwann cell processes, were embedded in the dense layers of collagen fibrils. The interior of the corpuscle was separated into small compartments by cell processes extended from the capsule. The axon varicosities contained numerous mitochondria. These fine structures of the corpuscles were similar to those of Ruffini corpuscles reported so far in other regions. Both Pacini-type and Ruffini-type corpuscles were clearly demonstrated by histochemistry for ChE. Inasmuch as the staining feature of corpuscles was different from each other, the distribution pattern of corpuscles in the joint capsules could be obtained by examining semi-serial sections. Pacini-type corpuscles were mainly found in the synovial layer, while Ruffini-type corpuscles were mainly located in the fibrous layer of the joint capsule. Both types of corpuscles were located near the median nerve on the flexor side of the joint. The reaction products of ChE activity were located in the peri-axonal as well as inter-lamellar spaces of Pacini-type corpuscles, and in the peri-axonal region as well as around Schwann cell processes of Ruffini type corpuscles. No definite reaction product was found within axon terminals. Some reaction products were also found in the rough endoplasmic reticulum and/or nuclear envelope, suggesting that ChE is synthesized by Schwann cells. The significance of these sensory corpuscles with regard to the deep sensation in the joint capsule was discussed from the point of view of the electro-physiological characteristics of the corpuscles. PMID- 4031575 TI - [Bone changes with long term administration of low dose 1-34 human PTH on adult beagles]. AB - It has been suggested that prolonged administration of low dose PTH could exert an anabolic effect on the bone. The effects of near-physiological dose of PTH injection on trabecular and cortical bones were studied in normal young adult beagles. Twelve 18 month-old male beagle dogs were equally divided into 4 groups by body weight. The 1st group serving as the control was subcutaneously injected with 1 ml of normal saline, and the 2nd, the 3rd and the 4th groups were also subcutaneously injected with 1.25, 5.0, 20.0 unit/kg/day of synthetic 1-34 human PTH respectively everyday for 15 weeks. Then, over the following 8 weeks, administration of all vehicle and drugs was withdrawn. After double bone labeling, iliac bone and rib biopsies were taken before and after the drug administration and after the withdrawal. The effects were evaluated with blood chemical and hormonal analysis and bone histomorphometry. No significant changes were noted in serum Ca, P, PTH, calcitonin and 1,25 (OH)2 vit.D levels and A1-P activities with some exceptions. Bone histomorphometry on trabecular bone showed remarkable and statistically significant elevation of formation surface, active formation surface, mineral appositional rate, labeled surface and bone formation rate. On the other hand, bone resorption rate and some other resorption parameters showed a significant elevation but trabecular bone volume showed no significant increase. In cortical bone, the bone dynamics were essentially equal to trabecular bone. But by the increase of bone turnover rate, cortical porosity rate increased. After withdrawal of drug administration, the bone turnover rate went down and a rate of cortical porosity returned to normal level. From these results it was postulated that PTH was effective in activating low remodeling of the skeleton. PMID- 4031576 TI - [Experimental study of hypertrophy of the femoral head--with special reference to the effects of the surgical procedure on the hip joint]. AB - This experimental study was performed to clarify how a surgical procedure to the hip joint causes hypertrophy of the femoral head. Young rabbits were used for this experiment. The following results were obtained. In the rabbits with sectioned ligamentum teres, some cases showed complete dislocation on X-ray. The incidence of the hypertrophy of the femoral head was very low in this group. Except in these rabbits with dislocation, the hypertrophy of the femoral head appeared in any group subjected to surgical procedure, and at especially high rates in those subjected to the section of ligamentum teres and/or edge resection of acetabular cartilage. In the cases in which the edge of the acetabular cartilage was resected, and in other cases of surgical procedure as well, acetabular dysplasia often resulted. In these cases the hypertrophy of the femoral head was observed more frequently than in others. In summary, surgical procedure to the hip joint and postoperative abnormal stress to the femoral head contribute to the development of the hypertrophy of the femoral head especially in the cases in which acetabular factors are not negligible. PMID- 4031577 TI - [The sagittal curvature of spine in idiopathic scoliosis--its morphological features and the correlation among sagittal and frontal curvatures and rotation of apical vertebra]. AB - The change in sagittal curvature especially in thoracic kyphosis of idiopathic scoliosis patients, was analyzed and discussed. Those patients who had scoliotic deformity with typical vertebral rotation only in thoracic spine (ST group), showed significant decrease compared to normal person in thoracic kyphosis, but no difference in lumbar lordosis. Those suffering from scoliotic deformities with typical vertebral rotation in thoracic and lumbar spine showed a significant decrease in thoracic kyphosis and an increase in lumbar lordosis. However those changes in sagittal curvature were not found in FT group patients, who had scoliotic deformity without vertebral rotation. In conclusion, it is not the frontal curvature but the vertebral rotation which influenced the sagittal curvature of spine in patients with idiopathic scoliosis. PMID- 4031578 TI - [A roentgenographical study on the aging process of alignment of the lower extremities in children--with special reference to pain in the lower extremity]. AB - To date, detailed reports are not available in large number concerning the alignment of lower extremities of children. Moreover, those already published are primarily concerned only with normal children, failing to make a sound comparison of lower extremity alignment between normal children and children with complaints about lower extremity alignment. Following is the summary of extensive research the author has done by comparing statistical data obtained--such as measurements of condylar distance, malleolar distance, and alignments of lower extremities- from 269 cases of normal children (538 lower extremities), from 2 years to 15 years, and 173 cases of children with pain (215 lower extremities), from 3 years to 15 years. Most of the children aged five years and older, whose main complaint is pain in their lower extremities, were found to show significant variations in the alignment of their lower extremities and were compared to normal children. When the intercondylar distance is greater than 10 mm, it is imperative to carefully investigate the alignment of the patient's lower extremities, because the pain is almost always found due to the malalignment. Bow legs and knock knees are not only deformity but also frequently accompanied by pain. Therefore, Lanz's method is most useful to evaluate bow legs and knock knees. PMID- 4031579 TI - [Biomechanical studies of the lateral collateral ligaments of the ankle using amputated limbs]. AB - In order to study the biomechanical behavior of the lateral ligaments around the ankle joint, strains on the anterior talofibular and the calcaneofibular ligaments were measured under adduction and supination loads. The amount of anterior shift of the talus was also examined under anterior "drawer" force. Specially designed omega-shaped transducers and jig sets to hold a leg and to give various loads to the foot were used for the experiments. Twenty human cadaver specimens of various ages were subjected for the study. The results showed the importance of not only the anterior talofibular ligament but also the calcaneofibular ligament as the stabilizer of the ankle joint and that the calcaneofibular ligament plays an important role in adduction, and the anterior talofibular ligament in both adduction and supination. Transection studies of the ligaments revealed that the calcaneofibular ligament is responsible to some extent for producing positive anterior drawer sign for which, as hitherto considered, the anterior talofibular ligament is the main factor. PMID- 4031580 TI - [The role of protein and hyaluronic acid in the synovial fluid in animal joint lubrication]. AB - The purpose of this investigation was to study the role of protein and hyaluronic acid of synovial fluid in the animal joint lubrication. The D-fraction (0.2 micron up to 0.8 micron) from the bovine synovial fluid showed the lowest friction coefficient and contained about 20% protein and 70% hyaluronic acid of the synovial fluid. Protein but not hyaluronic acid of this fraction had lubricating ability, and the protein but not hyaluronic acid could support the lubricating film thickness. By electron microscopic observation hyaluronic acid was 2,000A-5,000A formless mass and the protein complex that had lubricating ability was 200A-300A spherical particle. Through these results I presume that hyaluronic acid enclose the spherical protein particles in its network like a cage of the roller-bearing and the particles can rotate freely like rolling elements of the roller-bearing. It was suggested that the roller-bearing mechanism was performed along with elastohydrodynamic lubrication in animal joint. PMID- 4031581 TI - [Influence of intraarticular continuous perfusion of physiological saline on chondrocytes]. AB - Physiological saline, which is generally used in arthroscopic examination and operation, is not physiological in the synovial joints. This paper discusses metabolic changes in the articular cartilage following continuous intraarticular perfusion with physiological saline, in comparison with in vitro findings. Fourty rabbits weighing approximately 3 kg were intraarticularly and continuously perfused with saline at a rate of 250 ml/hour. Articular cartilage of the femoral condyle was collected for measurement of 35SO4 radioactivity by liquid scintillation spectrometry. Incorporation of 35SO4 showed increment in perfused articular cartilage as compared with the controls after one hour. Namely, glycosaminoglycan synthesis of chondrocytes was accelerated temporarily by continuous perfusion of saline, and it was recovered twenty-four hours after perfusion. In addition, histological and biomechanical test showed no remarkable changes. But, these effects will be expanded by the presence of degenerated articular cartilage. Continuous perfusion of physiological saline changes the physiological circumstance for articular cartilage, and influences on the chondrocytes' metabolism temporarily. PMID- 4031582 TI - [The effect of aging on blood pressure and hemodynamic parameters in 1650 cases of systolic and diastolic hypertension]. PMID- 4031583 TI - [Echocardiographic study on morphological abnormalities of the tricuspid valve in relation to the development of tricuspid regurgitation]. PMID- 4031584 TI - [Effects of sublingual nifedipine on hemodynamic responses to exercise in patients with myocardial infarction]. PMID- 4031585 TI - [Three cases of immunoblastic lymphadenopathy associated with marked hypocomplementemia]. PMID- 4031587 TI - [Kearns-Shy syndrome associated with choreic movement, primary hypogonadism, and brain CT abnormalities]. PMID- 4031586 TI - [A case of adenocarcinoma complicating Barrett's esophagus]. PMID- 4031588 TI - [A case of paragonimiasis miyazakii appearing with bilateral pneumothorax, effusion and alternating chest pain--a review of 82 cases reported in Japan]. PMID- 4031589 TI - [A case of Cushing's disease associated with glucocorticoid resistance]. PMID- 4031590 TI - Tourniquet pressure: the effect of limb circumference and systolic blood pressure. AB - Complications attributable to direct pressure may result from the use of pneumatic tourniquets during surgical procedures. Traditional estimates have determined the pressures employed rather than the minimal pressure necessary to produce a bloodless field. To determine this pressure, pre-operative and post operative systolic blood pressures and the tourniquet pressure at which capillary bleeding occurred were measured in a group of patients undergoing elective surgery of the upper and lower limbs. From these results two equations were derived, one for each of the upper and lower limbs, which give the minimum tourniquet pressures to produce bloodless fields. In an average sized, normotensive patient, 200mm Hg was found to be adequate for the upper limb and 250mm Hg for the lower limb. PMID- 4031591 TI - Effects of regional intravenous guanethidine block in posttraumatic cold intolerance in hand amputees. AB - In twenty-four patients with intolerance to cold after partial or complete finger amputations, lower skin temperature together with cold and vibration allodynia (allodynia = pain due to a non-noxious stimulus to neural skin) were found in the cold intolerant area compared with the corresponding area in the uninjured hand. When treated with regional intravenous guanethidine block nine patients became free from symptoms for up to twelve weeks, which is longer than would be expected from the duration of the known pharmacological effects of guanethidine. The patients had several features in common with reflex sympathetic dystrophies, and we suggest that neurogenic rather than vascular disturbances are mainly involved in the post-traumatic cold intolerance syndrome. PMID- 4031592 TI - Venous occlusion plethysmography in patients with cold related symptoms after digital salvage procedures. AB - Fourteen patients who had undergone microsurgical salvage of one or more digits were interviewed and examined. An assessment of sensitivity to cold is defined as cold intolerance and correlated with nerve function and arterial inflow measured by venous occlusion plethysmography. No relationship between arterial inflow and cold intolerance nor nerve function was found. There was, however a tendency for worsening cold intolerance to be associated with poorer nerve function. Half the salvaged digits had arterial inflow greater than the contralateral control digit. PMID- 4031593 TI - Pattern of contracture and recovery following ischaemia of the upper limb. AB - 196 cases of Volkmann's Ischaemic Contracture of the upper limb with well established ischaemia are presented. In all cases tight external circumferential splintage was the primary factor. 59.2% of these patients had been initially treated by "bone setters". 54.6% had fractures of the forearm; supracondylar fracture of the humerus was seen in 10.7% and 17.9% had no evidence of bone or joint injury. Different patterns of ischaemic contractures are recognised and the severity of the contracture is found to be related to the extent of paralysis. Sensory recovery occurs in a proximodistal direction even following total ischaemia and degeneration of the nerve. Motor recovery, however, does not seem to take place. Sensory recovery in the forearm proceeds rapidly in the first six months; thereafter it is less significant. However, the sensory recovery in the hand is significant only after more than twelve months. Since sensory recovery occurs even after total ischaemic degeneration of the nerve it is postulated that such nerves recover and regenerate in course of time. PMID- 4031595 TI - Anatomical study of the ulnar nerve in the hand. AB - This anatomical study is based on the dissection of fifty adult hands. The classic configuration of the ulnar nerve was found in thirty-nine cases out of fifty, and in eleven cases there were variations with respect to division. The levels of division of the different branches were precisely determined by an analysis of variations in the areas of muscular innervation. PMID- 4031594 TI - Intersynovial communication between the tendon sheaths of the extensor pollicis longus and extensor carpi radialis brevis muscles. AB - A communication was found between the synovial sheaths of the extensor pollicis longus and the extensor carpi radialis brevis tendons. The opening was at the level of the proximal row of carpal bones and permits passage of synovial fluid between the sheaths of these muscles. PMID- 4031596 TI - Subtotal reconstruction of the thumb by transposition of index finger. AB - A case of subtotal reconstruction of the thumb is described. The reconstruction was carried out as a staged procedure with an intact index finger transposition, followed by opposition transfer using the abductor digiti quinti muscle after three weeks. Twenty-eight months postoperatively, power grip and precision grip were restored despite destruction of the thenar muscles. PMID- 4031597 TI - The osteocutaneous pedicle forearm flap. AB - Two patients treated by an osteocutaneous radial island flap with retrograde blood flow are described. Rotation of the flap and its distal vascular pedicle by nearly 180 degrees caused no impairment of the arterial flow, but it may interfere with the venous return through the radial veins, as observed in one of our cases. Therefore, it is safer to include in the skin flap an additional vein, suturing it to a superficial vein in the recipient zone, thus ensuring normal venous flow to the flap as well. The purpose of this paper is to present two patients treated by the use of an osteocutaneous radial artery forearm flap. PMID- 4031598 TI - Sensitivity following volar V-Y plasty for fingertip amputations. AB - The volar V-Y plasty is a well accepted method of management for transverse fingertip amputations. It has been suggested by some authors and assumed by some surgeons that fingertip sensation is nearly normal following the procedure. Sixteen patients with twenty fingertip injuries in our series reported an average estimate of sensitivity of 73% of normal. There was diminished sensation to testing by two-point discrimination and/or von Frey monofilament testing in all fingertips when compared to the contralateral digit. Eight patients (twelve fingertips) reported hypersensitivity, particularly cryalgia. We conclude that sensation is not normal in almost all fingertips treated by V-Y plasty for transverse amputations. PMID- 4031599 TI - The triradiate incision. PMID- 4031600 TI - Closed rupture of flexor profundus tendon in the palm. AB - Closed ruptures of flexor tendons are rare. Most of them are associated with some underlying pathology. This is a case report of closed rupture of FDP tendon to the little finger in the palm at the level of the lumbrical origin. After extensive search of literature we could not find a similar case. PMID- 4031601 TI - Rheumatoid arthritis at the base of the thumb treated by trapezium resection or implant arthroplasty. AB - A clinical review is presented of patients with disabling rheumatoid arthritis at the base of the thumb treated by resection of the trapezium or by implant arthroplasty. Both methods resulted in good relief of pain, and the patients experienced better hand function. There were no great differences in results between the two methods. PMID- 4031602 TI - Salvage of the destroyed wrist. AB - Two cases of complex limb threatening destruction of the wrist region and their reconstruction are described. The role of external fixation and composite vascular grafts in controlling infection and achieving bony union is outlined. PMID- 4031603 TI - Swanson silastic wrist arthroplasty. A retrospective study of fifteen cases. AB - A retrospective study of fifteen Swanson silastic wrist replacements for rheumatoid arthritis (fourteen cases) and osteoarthritis (one case), with a mean follow up period of 28.3 months showed an increase in function in fourteen cases and no change in one case. An increase in range of movement was present in six cases, with no change in seven. Pain was improved in fourteen cases and unchanged in one case. Grip strength was improved or unchanged in twelve cases. There were two cases of prosthesis fracture. PMID- 4031604 TI - The relationship of the double crush to carpal tunnel syndrome (an analysis of 1,000 cases of carpal tunnel syndrome). AB - In this series of 1,000 cases of carpal tunnel syndrome (888 patients) there is a statistically significant incidence of bilaterality in patients with cervical arthritis. There is also a statistically significant increase in the incidence of diabetes mellitus over the general population. These findings lend further support to Upton's Double Crush hypothesis. Further, the double crush syndrome predisposes to bilateral carpal tunnel syndrome and may be an important prognostic factor. It may also be an explanation for some of the failures following carpal tunnel surgery and lead surgeons to look for other associated systemic diseases or mechanical blocks, when attempting to alleviate recalcitrant symptoms. PMID- 4031606 TI - An experimental study of instability during supination and pronation of the fractured scaphoid. AB - Rotatory instability of scaphoid fractures was studied by a method not used previously. On two fresh specimens the scaphoid bone was fractured by osteotomy, and the fracture was fixed by a Hoffmann apparatus extending from the distal radius to the 1st, 2nd and 3rd metacarpals. This permits free rotation in the forearm. The scaphoid fragments were marked by Kirschner wires. No movement occurred between the fragments when supination/pronation was kept within the normal range of movement. PMID- 4031605 TI - Fractures of the hook of the hamate. AB - Fractures of the hook of the hamate are rare injuries. Six new cases are presented; the most usual mechanism is probably a direct blow to the area of the hook. The diagnosis, which can only be made by special roentgenographic techniques is usually missed at the acute phase. Most of the cases are diagnosed when painful non-union, fraying tendinitis of the flexor tendons to the ulnar fingers, ulnar or median nerve deficits appear. The adequate treatment is usually excision of the hook fragment. PMID- 4031607 TI - Treatment of scaphoid nonunion by volar inlay distal radius bone graft. AB - Volar inlay corticocancellous bone grafting is an accepted method of treatment for symptomatic nonunion of the carpal scaphoid. Performance of this procedure with a radial graft without styloidectomy yields results comparable to those obtained with iliac grafting. This permits the operation to be performed through a single incision. The elimination of the need for iliac dissection avoids morbidity associated with the iliac exposure. PMID- 4031609 TI - Fractures of the trapezium. A report on three cases. PMID- 4031608 TI - Replacement of the proximal portion of the scaphoid with spherical implant for post-traumatic carporadial arthritis. AB - Nineteen spherical prosthetic replacements have been performed in eighteen non service patients for osteonecrosis of the proximal scaphoid--with carporadial arthritis. One period of observation postoperative was for seven weeks only. Two procedures failed in the same patient. The patient with Preiser's disease is too recent to permit definitive conclusions on follow-up. Each of the other fifteen patients followed for an acceptable period are considered to have a good or satisfactory result. PMID- 4031610 TI - Irreducible dislocation of the distal interphalangeal joint. PMID- 4031611 TI - Compound dislocations of four metacarpophalangeal joints. AB - A case of compound dorsal dislocation of four metacarpophalangeal joints is presented. The use of early joint motion and extension block splinting resulted in an excellent range of motion in this uncommon injury. PMID- 4031612 TI - Nerve tumours in the upper limb. A clinical review. AB - Tumours arising from the peripheral nerves in the upper limb are rare. This paper reviews eighteen such cases and the clinical outcome. Problems of pre-operative diagnosis are emphasized. PMID- 4031613 TI - Lymphangiosarcoma of the hand arising in a pre-existing non-irradiated lymphangioma. AB - Lymphangioma is an uncommon lesion which is widely believed not to undergo malignant change. Lymphangiosarcoma is even rarer and most of the cases reported in the literature were encountered in the setting of chronic lymphoedema, although occasional cases have been reported in irradiated lymphangiomata. This brief communication describes a case of multifocal lymphangiosarcoma arising in a non-irradiated, long standing lymphangioma of the hand. To our knowledge no similar case has been reported previously in the English literature, which is briefly reviewed. PMID- 4031614 TI - Congenital anomalies of the little finger. AB - Clinical features of congenital hypoplastic and extension contractures of the little finger were studied. There are eight groups. Characteristic features of each group are described. Each type has distinguishable clinical features in typical cases, but in some cases the condition of shortening of the phalanges and narrowing of the joint space is not clear. PMID- 4031615 TI - Dysplasia epiphysialis hemimelica an unusual case of macrodactyly of the thumb. PMID- 4031616 TI - Congenital absence of the scaphoid in the "VATER" association. AB - A rare carpal anomaly is reported in a patient with multiple congenital abnormalities. A literature search reveals few such cases, but a characteristic clinical picture emerges. Patients with this deformity should be carefully examined to exclude other congenital abnormalities. PMID- 4031617 TI - Problems in rheumatoid wrist fusion. PMID- 4031618 TI - The occult dorsal carpal ganglion. AB - Chronic wrist pain has many causes, the diagnosis of which is often difficult. Clinical and anatomical research in this area has replaced the diagnosis of "wrist sprain" with a differential diagnosis including carpal chondromalacia, dynamic carpal instability, positive and negative ulnar variance, triangular fibrocartilage complex injuries, and early carpal avascular necrosis. The ubiquitous dorsal ganglion can also cause chronic wrist discomfort and the diagnosis of "occult dorsal carpal ganglion" should be included in the differential diagnosis. Nine patients with chronic wrist pain were diagnosed clinically as having an occult dorsal carpal ganglion despite the absence of a palpable mass. Each was treated by limited dorsal capsulectomy with excision of a small portion of the dorsal scapho-lunate ligament, and small intracapsular ganglia and/or cystic mucinous degeneration of the capsule were found in all nine patients. Of the eight patients available for follow-up examination, the preoperative pain was relieved in seven of the eight and no recurrences were noted at follow-up averaging six months. PMID- 4031619 TI - Pseudogout of the wrist presenting as acute median nerve compression. AB - Two cases are reported of acute median nerve compression due to calcium pyrophosphate deposition in the wrist, masquerading as a septic condition. There have been recent reports in the literature of the effects of calcium pyrophosphate in joints of the upper limb (Resnick 1983 and Hensley, 1983) These conditions are uncommon and the presentation and initial symptomatology of our case led in the first patient to misdiagnosis and an unnecessary operation, which was avoided in the second case. PMID- 4031620 TI - Acute calcification in the fingers. AB - A patient with acute calcification of the proximal interphalangeal joint is presented to emphasize its importance in the differential diagnosis of acute infection in the finger. The diagnosis is made both clinically and by x-ray. The calcification may not be seen on standard views and oblique views may be necessary. Treatment is conservative by immobilisation and the injection of local anaesthetic. PMID- 4031621 TI - An unusual hand infection in a child--remember herpes! PMID- 4031622 TI - Preliminary report on a new technique to aid diagnosis of some disorders found in hands. AB - This preliminary report proposes to show that an objective auscultatory method exists as an aid to diagnosis of some hand conditions. The signals so produced are both distinctive and reproducible. The conditions investigated were:- Cavitation finger clicks; Trigger finger; normal crepitus and the crepitus of de Quervain's tenosynovitis. PMID- 4031623 TI - An arm elevating dressing. AB - An essential aspect of management of upper limb trauma (including burns), infection, and surgery, is elevation to reduce tissue swelling and to rest the injured part. Surgeons dealing with upper limb pathology each have their own method of elevating the arm. I wish to describe a type of arm elevating support which is used primarily for elevation of the upper limb postoperatively, but can be used as a sling in the ambulant patient. PMID- 4031624 TI - Skin hook: the Brown-Burr modification of the Gillies single hook skin retractor. PMID- 4031626 TI - Ulnar tunnel syndrome. PMID- 4031625 TI - Severe mincer injuries. PMID- 4031627 TI - Dupuytren's contracture which resolved following a traumatic incident. PMID- 4031628 TI - Exercise-induced hypercalcemia and the calciotropic hormones. AB - Sixteen healthy male volunteers exercised on a bicycle ergometer starting at 40% Vo2max and progressing at 5-minute intervals up to 75% Vo2max over a 20-minute period. Blood was drawn from an indwelling venous catheter at baseline, at 5 minutes through 20 minutes, and at 10 and 20 minutes after the exercise was ended. Significant increases (which returned toward baseline in the rest period) were observed during the exercise period in total calcium and calcium ion activity, phosphate, potassium, magnesium, albumin, and lactic acid levels. Plasma volume (based on hematocrit value) decreased during the exercise period. Serum parathyroid hormone levels decreased and calcitonin levels increased at the early period of the short-term exercise. Although hemoconcentration was of sufficient magnitude to explain the change in calcium ion activity, the increase in potassium and phosphate were caused in part by additional factors. PMID- 4031629 TI - Activated charcoal in theophylline intoxication. AB - To test the hypothesis that orally administered activated charcoal alters the elimination kinetics of intravenously administered theophylline, six dogs were twice infused with theophylline, 28 mg/kg, over 20 minutes 1 week apart. In a random sequence separated by 1 week, they received either activated charcoal, 30 gm in a water suspension or water only through a nasogastric tube every 2 hours after theophylline infusion, for a total of four doses. The time needed for plasma levels to fall below 20 mg/L was approximately 5 hours regardless of charcoal treatment. However, activated charcoal decreased theophylline halflife from 4.02 to 2.76 hours and volume of distribution from 0.72 to 0.61 L/kg. We conclude that although activated charcoal hastened the elimination of theophylline in dogs, the usefulness of orally administered activated charcoal in the treatment of theophylline overdose may be limited by the inability to shorten the time during which plasma levels are toxic. PMID- 4031630 TI - Parallel induction of IgE-mediated Ascaris antigen airway responses and increased carbachol airway reactivity in rhesus monkeys by infection with Ascaris suum. AB - In continuation of studies of four rhesus monkeys infected with Ascaris suum (J Lab Clin Med 101:864-872, 1983), we report the duration of IgE-mediated skin reactivity and airway responses to Ascaris antigen from 15 weeks to longer than 2.8 years. A second group of four rhesus monkeys was infected with A. suum ova after determination of the threshold of airway reactivity to carbachol. Evaluation of these animals confirmed the initial results of the first group of animals studied in relation to induction of skin and airway reactivity to Ascaris antigen. In addition, all animals developed increased airway reactivity, demonstrated by increased reactivity to lower concentrations of carbachol. We report this as a demonstration of induced IgE-mediated antigen airway responsiveness accompanied by induction of increased airway reactivity in a primate model. The increased airway reactivity does not appear related to the induction of IgE antibody. PMID- 4031631 TI - Pneumococcus-induced thrombocytopenia in rabbits. AB - Thrombocytopenia without other hemostatic changes is the most common coagulopathy associated with sepsis. We studied pneumococcus (PNC)-induced hemostatic changes, including thrombocytopenia, in rabbits. Nonviable PNC or saline solution was injected into rabbits preinfused with chromium 51-labeled platelets or iodine 125 fibrinogen. Blood was serially obtained for determination of platelet counts, 51Cr activity or 125I activity, and fibrinogen and fibrin degradation products. Lung, liver, and spleen tissues were counted for 51Cr or 125I activities per gram of wet tissue. PNC-challenged animals displayed profound thrombocytopenia from 0.5 to 48 hours with the mean nadir (-80% relative to the baseline) at 3 hours and a significantly (P less than 0.025) shortened 51Cr-platelet survival of 1.45 +/- 0.71 days vs. 2.72 +/- 1.09 days for saline-injected controls. Circulating fibrinogen level increased, whereas 125I-fibrinogen survival was unchanged (2.6 +/- 0.5 days in PNC-challenged vs. 2.8 +/- 1.0 days in saline-injected). No increased tissue deposition of either 51Cr-labeled platelets or 125I-fibrinogen was found. Rabbits infused with either serum, plasma, or saline solution after each was incubated with PNC all developed significant thrombocytopenia of less than 1 hour duration with maximal mean decreases relative to the baseline of -76% (P less than 0.001), -65% (P less than 0.0005), and -84% (P less than 0.0005), respectively. Inactivation of serum or plasma complement before PNC incubation or heat treatment after PNC incubation in serum or saline solution did not alter the thrombocytopenia. The thrombocytopenia-promoting activity was also trypsin resistant, did not require the presence of serum, plasma, or PNC capsular polysaccharide for its in vitro generation, and had a mol wt of 100,000 to 300,000. Therefore, PNC-induced thrombocytopenia, in the absence of other hemostatic changes, may be explained on the basis of the direct action of a PNC derived substance(s) on circulating platelets. PMID- 4031632 TI - Age is a determinant of the glomerular morphologic and functional responses to chronic nephron loss. AB - Loss of renal mass results in a compensatory increase in growth and function of remaining nephrons. Renal ablation also accelerates the expansion of mesangial matrix and the development of focal glomerulosclerosis (FGS) associated with aging. To determine whether age at the time of nephron loss influences the compensatory changes in function and the severity of subsequent glomerular lesions, immature rats (group I) and adult rats (group II) underwent right unilateral nephrectomy (Nx). Four weeks after Nx, compensatory renal growth and single nephron function showed a similar pattern in both groups. Five months after Nx, however, group I displayed significantly greater compensatory growth than group II, although both groups exhibited similar single nephron function. Moreover, group II demonstrated a significant increase in mean transcapillary hydraulic pressure difference (delta P) of approximately 5 mm Hg. Although both groups experienced accelerated expansion of mesangial matrix, significant FGS was detectable only in group I. Thus glomerular injury after Nx may result from factors other than alterations in glomerular hemodynamics. PMID- 4031633 TI - Platelet size and shape in hereditary giant platelet syndromes on blood smear and in suspension: evidence for two types of abnormalities. AB - Platelet size on blood smear is compared with platelet size and shape in suspension (i.e., whole blood and citrated platelet-rich plasma [PRP]) for normal donors and 16 patients with hereditary "giant" platelet syndromes (HGPS), including Bernard-Soulier syndrome (BSS) (seven patients), Montreal platelet syndrome (MPS) (three patients), May-Hegglin anomaly (one patient) and Rafael platelet defect (one patient). In whole blood platelet shape is normal for HGPS, but in PRP for 10 of 16 patients with HGPS there is a decrease in the proportion of smooth, discoid-shaped platelets (discocytes [D]). The platelets of all patients with HGPS had abnormally large mean volume (VT) and increased size on peripheral blood smear. Furthermore, 12 of 16 patients with HGPS, including six of seven donors with BSS, had abnormally large discocytes. The measured size of HGPS shape-changed platelets was compared with the size predicted from the size of the D by assuming that the relationship between the size of shape-changed platelets and D was the same as observed for normal donors. In this manner it was shown that for all donors with BSS and MPS, the shape-changed platelets are disproportionately larger than the D. In contrast, in the remaining patients with HGPS the size of the shape-changed platelets was consistent with the size predicted from the D. Examination of VT for MPS as a function of time after addition of 10 mumol/L adenosine diphosphate to PRP revealed an abnormal time course, thereby pointing to an abnormality in the mechanisms that regulate platelet size during shape change. With the lone exceptions of BSS and MPS, the size of platelets on blood smear was well correlated with the total platelet plasma membrane surface area as measured by the osmotic spherocyte method. Our observations point to two distinct abnormalities in platelet size in HGPS: a disproportion between the size of D and "shape-changed" platelets, which may be related to an abnormal shape change and which is observed only for MPS and BSS, and an abnormal increase in platelet size on blood smear, which appears to reflect the increased amount of platelet plasma membrane in other HGPS platelets. PMID- 4031634 TI - Comparison of the Koppitz and Watkins scoring systems for the Bender Gestalt Test. PMID- 4031635 TI - WAIS-R performance patterns of 565 incarcerated adults characterized as underachieving readers and adequate readers. PMID- 4031636 TI - The use of self-monitoring procedures with low IQ learning disabled students. PMID- 4031637 TI - Teaching poor readers to cope with maladaptive cognitive styles: a training program. PMID- 4031638 TI - Theoretical support for and use of original drawings and associative cues in vocabulary acquisition by children with severe reading disorders. PMID- 4031639 TI - The nonverbal dilemma. PMID- 4031640 TI - Spectral analysis of EEG differences between children with and without learning disabilities. PMID- 4031641 TI - Learning disabled readers' recall as a function of distinctive encoding, hemisphere processing and selective attention. PMID- 4031642 TI - Family history as an indicator of risk for reading disability. PMID- 4031643 TI - The future of the LD field. PMID- 4031644 TI - The future of the LD field: a survey of fundamental concerns. PMID- 4031645 TI - Characterization and catabolism of rat very high density lipoproteins. AB - A previously unrecognized lipoprotein of very high density was isolated from rat serum. During zonal ultracentrifugation of whole serum or of fractions from Sepharose 4B chromatography, a peak comigrating with a peak of cholesterol was found between the typical high density lipoproteins and the residual serum proteins. Centrifugation of chylomicrons, very low density lipoproteins, and high density lipoproteins, radio-iodinated in their lipid and protein moieties and mixed with serum, did not yield this peak. The pooled fractions contained about 85% protein. The remainder was lipid comprising cholesteryl esters, free cholesterol, triglycerides, phosphatidylcholine, and sphingomyelin. Polyacrylamide gel electrophoresis revealed bands in the region of apolipoproteins E and C as the major components. The composition suggested a lipoprotein, and this was substantiated by electron microscopy which showed particles with a mean diameter of 150 A. Their average hydrated density was 1.23 g/ml and the apparent molecular weight was 1.35 X 10(6). These very high density lipoproteins are characterized by a rapid catabolism as compared to high density lipoproteins. Within 10 min, 84% and 70% of intravenously injected 125I-labeled very high density lipoproteins were removed from plasma of male and female rats, respectively, and did not appear to be converted to lipoproteins of a different density class. Ninety-five percent of the removed 125I was recovered in the liver and the radioactivity per gram of tissue was also highest for the liver. Accordingly, the rate of clearance of 125I-labeled very high density lipoproteins was markedly reduced in functionally eviscerated rats. Radioautography revealed that most of the silver grains representing very high density lipoproteins were associated with hepatocytes and only about 1% was found over v. Kupffer cells. Uptake and degradation by freshly isolated rat hepatocytes were mediated by a saturable and specific binding site. Composition and metabolic pathway are compatible with a function of very high density lipoproteins in the transport of protein and lipids to the liver. PMID- 4031646 TI - Reduction in plasma cholesterol and increase in biliary cholesterol by a diet rich in n-3 fatty acids in the rat. AB - Cholesterol and lipoprotein metabolism were investigated in a group of rats fed a fish oil-supplemented diet, a rich source of n-3 fatty acids. For comparison purposes, other groups of rats were fed either safflower oil (n-6 fatty acids) or coconut oil (saturated fatty acids). Diets were isocaloric and contained identical amounts of cholesterol. Rats fed fish oils for 2 weeks showed a 35% lower plasma cholesterol level than rats fed safflower oil, who in turn showed a 14% lower plasma cholesterol level than those fed coconut oil. The fall in plasma cholesterol level with fish oils was associated with significant falls in low density and high density lipoprotein cholesterol levels, but with no significant change in the ratio of low density to high density lipoprotein cholesterol. The fatty acid compositions of plasma, hepatic, and biliary lipids showed relative enrichment with n-3 fatty acids, reflecting the composition of the diet. The fish oil diet increased the basal secretion rate of cholesterol into bile, but the bile acid secretion rate remained unchanged. It is suggested that n-3 fatty acids reduce the plasma cholesterol level in rats by increasing the transfer of cholesterol into bile. PMID- 4031647 TI - Effect of chenodeoxycholic acid on biliary and urinary bile acids and bile alcohols in cerebrotendinous xanthomatosis; monitoring by high performance liquid chromatography. AB - Biliary and urinary bile alcohol and bile acid composition has been determined by high performance liquid chromatography in patients with cerebrotendinous xanthomatosis before and after treatment with chenodeoxycholic acid. Most of the bile acids and bile alcohols in the bile and urine were separated in less than 30 min using a radial pack C18 muBondapak 5 micron particle size column with a mobile phase of acetonitrile-water-methanol-acetic acid 70:70:20:1 (v/v/v/v) at a flow rate of 2 ml/min, and a refractive index detector. Before treatment, cholic acid (49%) and 5 beta-cholestane-3 alpha, 7 alpha, 12 alpha, 25-tetrol (27%) were the major biliary bile acid and bile alcohol, respectively, but were not detected in the urine of five patients. 5 beta-Cholestane-pentols were, instead, the major urinary bile alcohols with 5 beta-cholestane-3 alpha, 7 alpha, 12 alpha, 23 xi, 25-pentol (56%) predominating. Whereas 5 beta-cholestane-3 alpha, 7 alpha, 12 alpha, 24S,25-pentol was not detected in the bile, it was isolated in the urine of all patients (27%). The only urinary bile acid isolated by high performance liquid chromatography was nor-cholic acid. After 1 month of treatment with chenodeoxycholic acid, 0.75 g/day, chenodeoxycholic acid became the major bile acid in the bile of all patients (71%) along with its metabolite, ursodeoxycholic acid (21%). Cholic acid and 5 beta-cholestane-3 alpha, 7 alpha, 12 alpha, 25 tetrol were drastically reduced and were only 3% each. The excretion of 5 beta cholestane-pentols in the urine was also drastically reduced from 130 mg/day to 15 mg/day. PMID- 4031648 TI - Contribution of vesicular and micellar carriers to cholesterol transport in human bile. AB - A nonmicellar, bile salt-independent mode of cholesterol transport in human bile involving phospholipid vesicles was recently reported by our group. In the present study, we have investigated the relative contribution of the phospholipid vesicles and mixed bile salt-phospholipid micelles to cholesterol transport in human hepatic and gallbladder biles. The vesicles (ca 800 A diameter) were demonstrated by quasi-elastic light scattering (QELS) in fresh bile and after chromatography. Gel filtration under conditions that preserved micellar integrity demonstrated that biliary cholesterol was associated with both vesicles and micelles. At low bile salt concentration, the vesicular phase was predominant and most of the cholesterol was transported by it. With increasing bile salt concentrations, a progressive solubilization of the vesicles occurred with a concomitant increase in the amount of cholesterol transported by micelles. The vesicular carrier may be of particular biological significance for cholesterol solubilization in supersaturated biles. PMID- 4031649 TI - Solubilization of the 17 alpha-ethinyl estradiol-stimulated low density lipoprotein receptor of male rat liver. AB - Pharmacological doses of 17 alpha-ethinyl estradiol induce a low density lipoprotein (LDL) receptor in the liver of male rats. Our aim was to solubilize this receptor. Isolated liver membranes (8,000-100,000 g fraction) from male rats treated with 17 alpha-ethinyl estradiol and from control rats were solubilized in 1% (w/v) Triton X-100. Using Amberlite XAD-2, more than 90% of the detergent was then removed. Liposomes were prepared by precipitating the solubilized proteins with acetone in the presence of phosphatidylcholine. The receptor activity of these liposomes was assayed using human 125I-labeled LDL. Filtration was used to separate bound from free 125I-labeled LDL. The assay was optimized; 0.25 mM CaCl2, 25 mM NaCl, pH 8.0, were chosen as the standard conditions. Binding of 125I-labeled LDL was dependent on Ca2+. Liposomes containing solubilized membrane proteins from treated rats displayed Ca2+-dependent binding which was 11 times higher than for control rats. The specific binding of 125I-labeled LDL was saturable with a Kd = 18 micrograms/ml. 125I-Labeled LDL was displaced by unlabeled lipoproteins containing apolipoproteins B and E and by dimyristoylphosphatidylcholine liposomes containing purified apolipoprotein E, but not by HDL3. The binding was abolished by pronase and was inhibited by suramin. Ligand blotting with 125I-labeled LDL revealed one band of protein with an apparent molecular weight of 133,000 daltons. These properties are characteristic of the low density lipoprotein receptor. PMID- 4031650 TI - Purification and characterization of bovine lipoproteins: resolution of high density and low density lipoproteins using heparin-Sepharose chromatography. AB - The selective and reversible adsorption of bovine low density lipoproteins (LDL) by heparin-Sepharose has been exploited as the critical step in a procedure for the preparative isolation of very low density lipoproteins (VLDL)/chylomicrons, LDL, and high density lipoproteins (HDL) from bovine plasma. Molecular size exclusion chromatography and isopycnic density gradient separation steps are also involved in the method described. The resulting HDL and LDL fractions are free from contamination by one another as judged by electrophoretic mobility in agarose gels. The major lipid and apolipoprotein compositions of the three resolved lipoprotein classes have been determined. PMID- 4031652 TI - Fluorescence studies of the binding of amphiphilic amines with phospholipids. AB - The binding characteristics of several amine drugs with dispersed phospholipids (phosphatidylcholine, phosphatidylserine, and phosphatidylglycerol) have been studied using the fluorometric method and 1-anilino-8-naphthalene sulfonate and 1,6 diphenyl-1,3,5-hexatriene as fluorescence probes. The results show that amphiphilic amines, such as chlorphentermine, interact with phospholipids via both ionic and hydrophobic forces. The ionic interaction, which occurs between the protonated amine group of the drug and the phosphate oxygen of the lipid, changes the amphiphilic characteristics of the lipid by reducing the number of negative charges on the lipid vesicles, and inhibits the Ca2+-dependent lipid hydrolysis by blocking the Ca2+ binding sites on the lipid vesicles. The hydrophobic interaction, which involves the nonpolar moieties of the drug and the lipid, is of primary importance to the overall drug-lipid binding stability. Drugs without a strong hydrophobic moiety, such as dopamine, do not interact with phospholipids. PMID- 4031651 TI - Alterations in the metabolism of lipids in ischemia of the liver and kidney. AB - The metabolism of lipids in the ischemic liver has been examined in the attempt to define the cause of the previously described loss of phospholipid and to determine whether additional alterations occur that may be related to the disturbances in membrane function. With 3 hr of ischemia, 30% of the cellular phospholipid was lost when measured either as phosphate in a lipid extract of the whole liver or as fatty acyl esters after separation by thin-layer chromatography of the major lipid classes in the same extracts. All phospholipid species were equally affected, and there was no accumulation of lysophospholipids. The loss of phospholipid acyl chains was not accompanied by an increased number of acyl esters as mono-, di-, or triglycerides. There was no increase in the size of the free fatty acid pool, and the content of long chain acyl CoA esters decreased by 50%. The acyl chain composition of the free fatty acid and neutral lipid pools changed, however, to resemble more closely that of the phospholipids. There was no change in the fatty acid composition of the phospholipids. The incorporation of intraportally injected [3H]arachidonic acid into total phospholipids was decreased upon reperfusion of liver that had been ischemic for only 20 min. These data are consistent with a loss of fatty acyl chains from the phospholipids into the free fatty acid pool. A few of these chains are incorporated into neutral lipids, but most are lost from the liver.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4031653 TI - Elevated levels of apolipoprotein E in the high density lipoproteins of human cord blood plasma. AB - The concentrations and lipoprotein distributions of apolipoprotein E (apoE) in normal human umbilical cord blood plasma were determined. The mean plasma apoE level of 95 neonates was considerably higher than that of 49 normal adults (58.1 vs 35.8 micrograms/ml). This elevation of apoE levels was in striking contrast to the lower than adult levels of cholesterol (72 mg/dl vs 185 mg/dl), triglyceride (37.8 mg/dl vs 97.6 mg/dl), and LDL cholesterol (25 mg/dl vs 110 mg/dl) in neonatal plasma. For the group of 95 neonates, the plasma apoE concentration correlated significantly with total plasma cholesterol concentration (r = 0.60), with LDL cholesterol concentration (r = 0.27) and with HDL cholesterol concentration (r = 0.50). Among the neonates, 87% of plasma apoE was associated with a less dense subfraction of high density lipoprotein compared to a mean of 58% for 30 normal adults. Thus, for neonates, despite hypolipidemia, the absolute concentration of apoE in HDL (50 micrograms/ml) was 2.5 times that of adults (20 micrograms/ml). We speculate that the very low level of neonatal VLDL, providing limited substrate for lipolysis, may result in retarded removal of apoE from plasma and the observed high level of apoE in neonatal HDL. We hypothesize that in the fetus and neonate, as has been demonstrated in abetalipoproteinemia, apoE rich HDL may functionally substitute for LDL in delivering cholesterol to cells. PMID- 4031654 TI - Linoleate-rich acylglucosylceramides of pig epidermis: structure determination by proton magnetic resonance. AB - The structure of the linoleate-rich acylglycosylceramides isolated from pig epidermis has been reinvestigated. Gas-liquid chromatographic analysis of the alditol acetates produced from the sugar component indicated that 90% of the hexose is glucose while the remaining 10% is galactose. The predominance of the beta-D-glucosyl group was confirmed by 360 MHz proton magnetic resonance spectroscopy. The magnetic resonance method was also used to prove that the ester linked linoleic acid is actually attached to the omega-hydroxyl group of the long chain hydroxyacid, not to the sugar as had been reported previously. A key spectral feature supporting this new structural assignment was a triplet at 3.82 ppm, which indicates methylene protons between another methylene and an ester linkage. After saponification, this signal moved to 3.33 ppm, a chemical shift expected for a methylene bearing a free hydroxyl group. Furthermore, all of the sugar ring protons could be accounted for both before and after acetylation. No evidence was found to suggest that an ester is attached to the sugar ring in the native material. It is concluded that the principal porcine epidermal acylglycosylceramide is 1-beta-D-glucosyl-N-(omega-O-linoleoyl) triacontanoylsphingosine. PMID- 4031655 TI - Synthesis and characterization of a highly fluorescent peptidyl phosphatidylethanolamine. AB - The synthesis of a fluorescent lipid for use in studies of immune recognition of model membranes is described. The molecule has the basic structure HAPTEN-SPACER LIPID, where fluorescein is the hapten, an oligopeptide (triglycine) is the spacer, and dipalmitoylphosphatidylethanolamine (DPPE) is the lipid. The spacer, which is necessary for immunological reactivity, is first linked via a peptide bond to DPPE. The free N-terminus of the peptidyl-DPPE is then reacted with 5 dichlorotriazinylaminofluorescein (DCTAF) to yield fluoresceinchlorotriazinyltriglycyl-DPPE (FG3P). The structure is confirmed by mass spectrometry and Fourier transform NMR. When FG3P is incorporated into phospholipid vesicles it retains the brilliant fluorescence and high-affinity immunological reactivity of fluorescein. The general synthesis scheme may prove useful in other membrane and lipoprotein applications. PMID- 4031656 TI - Synthesis of C-22, C-23-3H-labeled 3 alpha,7 alpha,12 alpha-trihydroxy-5 beta cholestane. AB - This report describes an efficient synthesis of C-22, C-23-(3)H-labeled 3alpha,7alpha,12alpha-trihydroxy-5beta-cholestane. - Somanathan, R., and S. Krisans. Synthesis of C-22, C-23-(3)H-labeled 3alpha,7alpha,12alpha-trihydroxy 5beta-cholestane. PMID- 4031657 TI - Notes on the breeding of the WHHL rabbit: an animal model of familial hypercholesterolemia. AB - We describe in this study a reliable method for the breeding of the Watanabe heritable hyperlipidemic (WHHL) rabbit. Placing a male and a female WHHL rabbit in the same cage for the purpose of mating resulted in only two pregnancies out of a total of 227 mating attempts (0.9%). After manually assisting the rabbits, 15% of the matings resulted in pregnancies. When the female rabbits were injected with 40 I.U. of human chorionic gonadotropin within 1 hr of this procedure, 56% of the matings resulting in pregnancies. We feel that the inherent difficulty in breeding the WHHL rabbit, a model for the disease familial hypercholesterolemia, can be significantly overcome by the methods discussed in this report. PMID- 4031658 TI - Spectrofluorometric studies of the lipid probe, nile red. AB - We found that the dye nile red, 9-diethylamino-5H-benzo[alpha]phenoxazine-5-one, can be applied as a fluorescent vital stain for the detection of intracellular lipid droplets by fluorescence microscopy and flow cytofluorometry (J. Cell. Biol. 1985. 100: 965-973). To understand the selectivity of the staining, we examined the fluorescence properties of nile red in the presence of organic solvents and model lipid systems. Nile red was found to be both very soluble and strongly fluorescent in organic solvents. The excitation and emission spectra of nile red shifted to shorter wavelengths with decreasing solvent polarity. However, the fluorescence of nile red was quenched in aqueous medium. Nile red was observed to fluoresce intensely in the presence of aqueous suspensions of phosphatidylcholine vesicles (excitation maximum: 549 nm; emission maximum: 628 nm). When neutral lipids such as triacylglycerols or cholesteryl esters were incorporated with phosphatidylcholine to form microemulsions, nile red fluorescence emission maxima shifted to shorter wavelengths. Serum lipoproteins also induced nile red fluorescence and produced spectral blue shifts. Nile red fluorescence was not observed in the presence of either immunoglobulin G or gelatin. These results demonstrate that nile red fluorescence accompanied by a spectral blue shift reflects the presence of nile red in a hydrophobic lipid environment and account for the selective detection of neutral lipid by the dye. Nile red thus serves as an excellent fluorescent lipid probe. PMID- 4031659 TI - Postnatal development of intestinal bile salt transport. Relationship to membrane physico-chemical changes. AB - The postnatal development of intestinal bile salt transport in the rat was examined using the villus technique. Jejunal uptake of taurocholate was linear with respect to incubation concentration at all study ages. Ileal uptake was linear with taurocholate concentration during the first 2 postnatal weeks; a curvilinear relationship indicating the presence of saturable transport appeared during the third week. With the appearance of ileal active transport at age 3 weeks, the Km (app) was constant at 0.49 mM, 0.59 mM, and 0.50 mM in 3-week, 4 week, and adult animals, respectively. The V(app) was 14.65 nmol X mg-1 (dry wt) X min-1 at 3 weeks and declined with age to 11.40 and 10.51 nmol X mg-1 (dry wt) X min-1 in 4-week and adult animals, respectively. The role of physico-chemical changes in the microvillus membrane in the development of ileal active transport was examined. With increasing postnatal age, microvillus membrane cholesterol content rose while the phospholipid content remained unchanged in both ileum and jejunum. Corresponding rises in the cholesterol/phospholipid ratio were observed in both sites. Simultaneously, the microvillus membrane fatty acid composition was changing from predominantly saturated to unsaturated species in both ileum and jejunum. The microvillus membrane fluorescence anisotropy (r) increased with postnatal age in jejunum when measured at 25 degrees C and 37 degrees C and ileum when measured at 25 degrees C; however, no change was noted in ileum when measured at 37 degrees C. Ileal active bile salt transport develops during the third postnatal week, and is associated with concurrent changes in membrane lipid composition and fluidity when measured at 25 degrees C.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4031660 TI - Stimulation by unsaturated fatty acid of squalene uptake in rat liver microsomes. AB - Supernatant protein factor (SPF) and anionic phospholipids such as phosphatidylglycerol (PG) stimulate squalene epoxidase activity in rat liver microsomes by promoting [3H]squalene uptake as well as substrate translocation (Chin, J., and K. Bloch. 1984. J. Biol. Chem. 259: 11735-11738). This process is postulated to be membrane-mediated and not carrier-mediated. Here we show that treatment of PG with phospholipase A2 in the presence of bovine serum albumin abolishes the stimulatory effect of SPF on epoxidase activity. Disaturated fatty acyl-PGs are not as effective as egg yolk lecithin PG in the SPF effect. These findings suggest an important role for the unsaturated fatty acid moiety of PG. We also show that at submicellar concentrations, cis-unsaturated fatty acids stimulate microsomal epoxidase activity whereas saturated fatty acids do not. This effect is due to an increase in substrate uptake which in turn may facilitate substrate availability to the enzyme. PMID- 4031661 TI - Kinetic properties of human milk bile salt-activated lipase: studies using long chain triacylglycerol as substrate. AB - Studies on the hydrodynamic properties of human milk bile salt-activated lipase (BAL) indicated that it is a monomer with molecular weight of 107,000. The presence of taurocholate (1 mM) did not lead to an association of the enzyme. The enzyme had a basal activity with trioctanoylglycerol and with shorter chain, but not with longer chain, monoacid triacylglycerols. Based on kinetic analyses, we suggest that the BAL-catalyzed lipolysis of long-chain triacylglycerol can be described to follow a compulsory sequential mechanism. The initial interaction of BAL with the activator (taurocholate) leads to a conformational change of the enzyme which facilitates the further interaction with the long chain triacylglycerol substrate in forming the enzyme-bile salt-substrate ternary complex. We also suggest that the binding of BAL with substrate involves direct interaction of the active site with the fatty acyl-chain of the triacylglycerol rather than with nonspecific hydrophobic interactions at the emulsion interface. PMID- 4031662 TI - Plasma phospholipid transfer protein enhances transfer and exchange of phospholipids between very low density lipoproteins and high density lipoproteins during lipolysis. AB - In order to determine the effects of a plasma phospholipid transfer protein on the transfer of phospholipids from very low density lipoproteins (VLDL) to high density lipoproteins (HDL) during lipolysis, biosynthetically labeled rat 32P labeled VLDL was incubated with human HDL3 and bovine milk lipoprotein lipase (LPL) in the presence of the plasma d greater than 1.21 g/ml fraction or a partially purified human plasma phospholipid transfer protein (PTP). The addition of either the PTP or the d greater than 1.21 g/ml fraction resulted in a 2- to 3 fold stimulation of the transfer of phospholipid radioactivity from VLDL into HDL during lipolysis. In the absence of LPL, the PTP caused a less marked stimulation of transfer of phospholipid radioactivity. Both the d greater than 1.21 g/ml fraction and the PTP enhanced the transfer of VLDL phospholipid mass into HDL, but the percentage transfer of phospholipid radioactivity was greater than that of phospholipid mass, suggesting stimulation of both transfer and exchange processes. Stimulation of phospholipid exchange was confirmed in experiments where PTP was found to augment transfer of [14C]phosphatidylcholine radioactivity from HDL to VLDL during lipolysis. In experiments performed with human VLDL and human HDL3, both the d greater than 1.21 g/ml fraction and the PTP were found to stimulate phospholipid mass transfer from VLDL into HDL during lipolysis. Analysis of HDL by non-denaturing polyacrylamide gradient gel electrophoresis showed that enhanced lipid transfer was associated with only a slight increase in particle size, suggesting incorporation of lipid by formation of new HDL particles. In conclusion, the plasma d greater than 1.21 g/ml fraction and a plasma PTP enhance the net transfer of VLDL phospholipids into HDL and also exchange of the phospholipids of VLDL and HDL. Both the transfer and exchange activities of PTP are stimulated by lipolysis. PMID- 4031663 TI - Plasma decay of chylomicron remnants is not affected by heparin-stimulated plasma lipolytic activity in normal fasting man. AB - In an earlier study it was shown that retinyl palmitate appeared to be a satisfactory label for the core of chylomicrons and their remnants. When chylomicrons were endogenously labeled with retinyl palmitate and pulse-injected into healthy donors, retinyl palmitate was cleared from plasma by a first order process. Its fractional decay constant was very similar to the fractional catabolic rate of VLDL triglycerides, a lipoprotein lipase-dependent process, and 2-3 times slower than hepatic chylomicron remnant uptake in experimental animals. We, therefore, investigated whether plasma clearance of retinyl palmitate-labeled chylomicrons is accelerated by enhanced plasma triglyceride hydrolysis produced by heparin administration. Five healthy subjects took retinyl palmitate by mouth and 5-6 hr later two units of plasma were obtained by plasma-pheresis. After storage for 42 hr, the units were pooled and separated into two equal volumes. The first half was injected into the donor and plasma retinyl palmitate and chylomicron triglyceride were measured for 3.5 hr (control study). Heparin was then given intravenously as a bolus followed by an infusion for 7 hr. A second retinyl palmitate clearance (postheparin study) was performed during the heparin infusion. Plasma lipolytic activity and retinyl palmitate and chylomicron triglyceride concentrations were measured serially. Total plasma lipolytic activity and hepatic triglyceride lipase activity were increased approximately 500-fold during postheparin studies, enhancing triglyceride decay 2.5- to 3-fold. Retinyl palmitate plasma decay, however, was unaffected. Retinyl palmitate plasma decay was a biexponential concentration-dependent function in eighty of ten pre- and postheparin studies with the first, rapid exponential accounting for 90 +/- 4% of total plasma retinyl palmitate decay.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4031665 TI - Potential bile acid metabolites. 9. 3,12-Dihydroxy- and 12 beta-hydroxy-5 alpha cholanoic acids. AB - Syntheses of the heretofore unreported 3 alpha, 12 beta-, 3 beta, 12 beta dihydroxy-, and 12 beta-hydroxy-5 alpha-cholanic acids of the 5 alpha-series, their methyl esters, and some related derivatives are described. In addition, allodeoxycholic (3 alpha, 12 alpha-dihydroxy) acid was prepared by a new route. The principal reactions involved were the stereoselective reduction of C-12 ketones with an amino-borane reagent and of a C-3 ketone with K-Selectride, and inversion of a 3 beta-tosylate derivative with N,N-dimethylformamide. PMID- 4031664 TI - Alkyl dihydroxyacetone phosphate synthase in human fibroblasts and its deficiency in Zellweger syndrome. AB - The cerebro-hepato-renal (Zellweger) syndrome is an autosomal recessive disorder biochemically characterized by the absence of morphologically distinguishable peroxisomes. Key enzymes involved in the biosynthesis of ether phospholipids, i.e., dihydroxyacetone phosphate acyltransferase and alkyl dihydroxyacetone phosphate synthase, are located in mammalian (micro)peroxisomes. We have previously shown a strikingly reduced activity of dihydroxyacetone phosphate acyltransferase in liver, brain, and cultured skin fibroblasts from Zellweger patients (Schutgens et al. 1984. Biochim. Biophys. Res. Commun. 120: 179-184). We have now extended these investigations by studying alkyl dihydroxyacetone phosphate synthase in cultured human skin fibroblasts. Enzymatic activity was determined by measuring the formation of radioactive alkyl dihydroxyacetone phosphate from palmitoyl dihydroxyacetone phosphate and [1-14C]hexadecanol as substrates. The enzyme was optimally active at pH 8.5 and was stimulated (about 2 3-fold) by the presence of 0.05% (v/v) Triton X-100. The apparent KM values for the enzyme in control fibroblasts amounted to 35 microM for palmitoyl dihydroxyacetone phosphate and 90 microM for hexadecanol. The reaction became inhibited at higher concentrations of both Triton X-100 and palmitoyl dihydroxyacetone phosphate. Control skin fibroblasts showed alkyl dihydroxyacetone phosphate synthase activity of 69 +/- 28 pmol X min-1 X mg-1 (n = 7), while fibroblasts from patients had an activity of only 6.3 +/- 1.7 pmol X min-1 X mg-1 (n = 7). Alkyl dihydroxyacetone phosphate synthase was also found to be deficient in tissue homogenates of Zellweger patients. The specific activity of this enzyme in liver, kidney, and brain homogenates from Zellweger patients was less than 15% of that in the corresponding tissues from controls. PMID- 4031666 TI - Fractionation of fecal neutral steroids by high performance liquid chromatography. AB - Fecal neutral steroids were fractionated by high performance liquid chromatography (HPLC) into three major fractions: 5 beta-H, 3-keto steroids; 5 beta-H, 3 beta-hydroxy steroids; and 5 alpha-H and delta 5-3 beta-hydroxy steroids. This separation was achieved in about 10 minutes, with greater than 97% recovery of standards in each fraction. Gas-liquid chromatographic quantitation of fecal steroids fractionated by either HPLC or thin-layer chromatography gave nearly identical results. A method using both C18 reverse phase and silica HPLC to purify radiolabeled sterols is also described. PMID- 4031667 TI - [Vascular function studies and management of lower-limb arteriopathy]. PMID- 4031668 TI - [Current status of the surgery of carotid stenoses]. AB - In a series of 472 operations performed in 420 patients between 1981 and 1982, the mortality rate was 1.1% in asymptomatic patients (stage 0) and 2.1% in patients with transient ischaemic attacks (stage I) or with minor neurological sequelae (stage III). The morbidity rate of serious sequelae was 1.05%. The long term mortality is 30% at 5 years and 50% at 10 years, in most of the major statistical studies. The major cause of death (more than 50%) is myocardial infarction. The study of the local evolution of the operated artery reveals that about 10% of the patients who survived between 5 to 10 years had a recurrent carotid artery stenosis. Comparative studies of the course of the atherosclerotic disease operated patients and in patients treated medically are difficult to evaluate. However, most authors agree with Fields that an operation is justified in asymptomatic patients and in those presenting transient ischaemic attacks, provided the mortality and morbidity rate is less than 3%. Finally, recent studies stress the value of non-invasive investigations for determining the prognosis of tight stenoses: in asymptomatic patients with tight stenoses, the risk of a cerebrovascular accident is 5 times greater than in patients with a minor stenosis. PMID- 4031669 TI - [Value of plethysmographic methods as a means of monitoring arteriopathies]. AB - Plethysmography provides an original solution to the study of arteriopathy, complementing other non-invasive investigational methods. The different fields of application are discussed, and the diagnostic and prognostic value of each of them outlined. Methods used include: pulsed plethysmography, measurement of segmental pressures, hyperemia test, irrigraphy and measurement of segmental blood flow. Principal advantages of the technique are undoubtedly the evaluation of global function, monitoring of therapy and, to some degree, prediction of course. PMID- 4031670 TI - [A few reflections on the practice of urban medical angiology. Activity, role, future]. AB - The author attempts to evaluate the practice of private medical angiologists. He presents the results of a survey conducted amongst his colleagues in the South of France and the Pyrenees and analyses the principal reasons for consultation from 6,900 cases seen in angiology practices. It seems that although vascular functional investigations take an increasingly large place in angiology practice, phlebology remains the predominant activity and the clinician is still very involved in therapy. Although the angiologist has defined his specificity, it is essential that he works within a team, in cooperation with the vascular radiologist and the vascular surgeon. PMID- 4031671 TI - [Hyperbaric oxygenation and arteriopathies]. AB - Hyperbaric oxygen (O.H.B.) in arteriopathies of the limbs was tested in 2 021 patients over a period of time extending from 1966 to 1983. Therapeutic pressure varied from 2 to 2.4 absolute atmospheres (A.T.A.) as it is specified using plethysmography. The therapeutic periods at a frequency of 1 or 2 per day according to clinical characteristics have 1 hour duration for a total of 30 therapeutic periods. No complication was observed using this technique. O.H.B. increased the oxygen debt by enriching the blood in O2. The plethysmographic controls showed in 40% of cases a transport of circulating masses from healthy territories in vasoconstriction to the non responding hypoxic territories. An over-oxygenation of the additional blood resulted in ischaemic zones. This study suggests that O.H.B. may be an important method of treatment of patients with asymptomatic arteriopathy. PMID- 4031672 TI - [Preliminary results of a prospective study of microcirculatory disorders in alcoholic fibro-cirrhosis. Relation to hyperestrogenism]. AB - In the course of alcoholic cirrhosis, the low incidence of occlusive arterial diseases in the lower limbs, as well as the analogy in skin lesions between cirrhosis and pregnant women, lead to believe that hyperestrogenism may be common origin of these skin lesions. Research of abnormal microcirculation in the nailfold and oestrogen's receptors have been performed in a cirrhotic (20) and hyperestrogenic (12) population. The capillaroscopic abnormalities have been as follows: fine and short capillaries, oedema slacked circulation, the underlying structure was pale with peripheral halo. These have been observed both in the cirrhotic and hyperestrogenic patients. These oestrogenic receptor in both populations seem mainly localised in the granulosa structure and are more numerous than normal. Capillaroscopic features on the cirrhotic patients were similar to those on hyperestrogenic patients. The presence of oestrogenic receptors in the skin bears no particular significance at the present time. PMID- 4031673 TI - [Does conjunctival biomicroscopy enable one to assess the microcirculatory activity of buflomedil?]. PMID- 4031674 TI - [Manual lymphatic drainage]. AB - Manual lymphatic drainage is non-invasive physiological method. Its real effectiveness still has to be demonstrated by means of a comparative quantitative experiment against other techniques. It is still difficult to apply for material reasons such as the small number of physiotherapists and the lack of inscription in the Social Security nomenclature. These two problems can only be resolved by a further development of the technique. PMID- 4031675 TI - [Management of severe hypertension in a patient with arteriopathy]. PMID- 4031676 TI - [Microvascular consequences of low distal blood perfusion rates]. AB - It is classical, in obstructive arterial disease, to be most concerned with the truncal arteries, although nutrition and exchanges occur at the level of the terminal vessels. The most important events occur in the muscles and in the skin, at the extremity of the limb and one wonders whether "ischaemic disease" could perhaps be summarized as the result of low perfusion rates. The laws of hydraulics are unusual in this situation, the microcirculation is autonomous and autoregulated. The architectonics are also unusual: the distribution into asymmetrical parallel networks explains the heterogeneity of the distribution in which stasis, conglutination and red cell rigidity, interstitial flooding and the rheological consequences play a major though unequal role in the skin and the muscle. The problems of the haematocrit, viscosity, surface tension or interface and the electrostatic potentials are more important at this level and they determine the therapeutic decisions. PMID- 4031677 TI - [The nail in vascular pathology]. AB - The nail is part of the ungual unit; it is affected indirectly and late in vascular disease. The authors recall the anatomy and the blood supply of the ungual unit and describe the alterations in terms of the level of the lesion. They describe the changes seen in systemic diseases such as the collagen disease, in vascular disease, venous, arterial and lymphatic disease and in vascular acrosyndromes. These alterations are often a result of several diseases, but may, nevertheless, help orient the diagnosis. PMID- 4031678 TI - [Compression in vascular pathology. Practical applications]. AB - A better use of the methods of compression in vascular disease would be based on a progression of the available techniques: fixed compression, elastic bandages, elastic stockings, so that one can pass from one degree to another, but only in the direction indicated, except in the case of regression of the disease, when treatment of the previous stage would be required. One should never replace elastic stockings by elastic bandages except in the case of regression, nor the bandage by the boot, except when the bandage fails. On the other hand, a favourable clinical evolution means that the boot can be replaced by the bandage, the bandage by the stocking, or directly from the boot to the stocking. The optimal choice of the method of compression is made from this progressive range on the basis of the evaluation of the severity of the vascular disorders. PMID- 4031679 TI - [Possible role of a cardiac factor in limiting the walking perimeter in the treadmill test in the arteritis patient]. AB - Electrocardiographic modifications appearing during a treadmill test undergone by 145 patients with arterio-sclerosis obliterans at stage II without coronary antecedents and with normal resting electrocardiograms were studied. Twenty per cent of the patients had to discontinue the test (slope 12%, 3,8 km/h). A repolarization anomaly of ischemia type appeared in 13% of the cases (19 patients) and a rhythm disorder in 1%. Hence systematic monitoring of the electrocardiogram during walking test can enable subjects with high coronary risk to be singled out. PMID- 4031680 TI - [Vascular functional exploratory methods enabling the assessment of the evolution of lower-limb arteriopathies in the critical phase. Pulpal pulsed signal, digital pressure, transcutaneous PO2 of the front of the foot. Preliminary notes]. AB - Various situations are defined in which viability of a lower limb is compromised and for which clinical data may be insufficient to assess any very short-term progressive tendency during medical or surgical therapy. Among techniques for exploration of vascular function, parameters of pressure and digital pulsatility and measurement of front of foot transcutaneous PO2 can be considered to be reliable means of determination of the degree of permanent ischemia. Their application to assessment of changes in course during therapy is proposed as a supplement to clinical data. PMID- 4031681 TI - [Evolution of vasomotor tone in chronic obstructive arteriopathy of the lower limbs]. AB - Progressive degradation in the appearance of digital plethysmogram tracings occurs during acute episodes of occlusive arteriopathies, and is of importance for establishing the diagnosis and the choice of therapy. The distal microvasculotissular score is of major interest during the stages defined by R. Fontaine in 1966. Changes are in fact those of rheologic factors in the terminal network. It is logical to incriminate variations in "tone" and of vasomotor response, the final relay being at the site distal to the circulatory units and their endothelial receptors. The problem should be envisaged at each stage in the course of the disease. Vasoplasticity is a function of the severity of the arteriopathy. PMID- 4031682 TI - [What key zones should be monitored as a function of the assessment of the initial lesion? Collateral pathways?]. AB - Key zones to be kept under surveillance are defined as a function of initial lesion features of operated or unoperated arteriopathy of lower limbs. Knowledge of these key zones resides in the anatomical knowledge of the supply network and of the physiopathology involved and its coming into play. Collateral circulations of infrarenal aortic obstructions are studied in detail, and then those that develop after femoral and tibial artery occlusions. Valid prediction of the ischemic risk can only be made after obtaining precise data on the re-entry effectiveness through this collateral circulation, allowing a prognosis to be established and a reasoned choice of therapy to be made. PMID- 4031683 TI - [Pulsatility, flow and metabolic diseases]. AB - Metabolic diseases, and particularly diabetes mellitus have a well-established vascular determinism. Diabetic arteriopathy is associated from its onset with elevated tissue blood flow at rest and blood and plasma hyperviscosity. These anomalies are corrected by the perfect equilibration of the glycemia with the artificial pancreas. In 8 to 28% of cases, according to the author, there is an original hemodynamic picture; the enhanced flow hyperpulsatile diabetic arteriopathy observed in a caricatural manner in ulcerated mutilating acropathies. The vasomotor inertia of the diabetic artery and the metabolic neuropathy suggest that surgery to increase blood flow might be of interest in diabetic patients, as a function of results of previous function tests. PMID- 4031684 TI - [The venous-arteriolar reflex]. AB - Cutaneous blood flow (Xenon clearance) and transcutaneous pO2 were simultaneously measured on the foot of normal subjects and patients suffering from severe arterial insufficiency of the lower limbs. When the subject is sitting, cutaneous blood flow decreases, as well in normal subjects than in most patients with arterial insufficiency. However, tc pO2 increases in sitting position, probably because local vasoregulation is abolished by local heating. Increase in tc pO2 in sitting position is higher in patients in whom tc pO2 was very low in lying position. In normal subjects, there is a positive correlation between cutaneous blood flow and tc pO2. This correlation do not exist in patients suffering from severe ischemia; it is likely that Xenon clearance actually measures total cutaneous blood flow, while tc pO2 constitutes an index of nutritional circulation. It is also possible that Xenon clearance is modified by changes in partition coefficient in ischemia areas. PMID- 4031685 TI - [The amplification factor of the Hillestad reactional hyperemia test as a function of glucose status, clinical status and ankle pressure index]. AB - Principles of the reactive hyperemia test are summarized, the method used defined and the amplification factor f described as the ratio of the post-ischemia amplitude of pulsed plethysmographic signal to its baseline amplitude before arterial occlusion. Values for this factor were determined in patients free from occlusive arterial lesions with or without glucose metabolism disorders, in cases after sympathectomy and in patients with lower limb arterial disease stage I-II and extensive occlusive lesions and in stage III-IV. The factor f is either the reflection of the state of vasodilation or vasoconstriction of the lower limbs studied, or the sign of a diabetic neuroangiopathy. Its study requires comparison of values in both limbs of the same subject. PMID- 4031686 TI - [Sympathectomy and microcirculation: physiopathologic reflections]. AB - Sympathectomy provokes vascular motor denervation, and drastically modifies the vasomotor equilibrium of the limbs which is also dependent on metabolic, humoral and myogenic factors. Therapeutic efficacy of sympathectomy is related to the state of activity and reactivity of these other factors. The fall in peripheral resistance resulting from the opening up of cutaneous arteriovenous anastomoses increases flow through a stenosis or bypass, with the tendency for development of the collateral circulation. Positive effects may be obtained also when trophic disorders exist, but there is the risk of a nutritional circulation steal in the presence of blood hyperviscosity, with the need for associated rheologic treatment. Indications are few in Raynaud's disease, except for digital arterial disease. PMID- 4031687 TI - [The irrigraphic profile, an orienting element in the indications for lumbar sympathectomy]. AB - A retrospective study of 108 case-reports of patients treated by lumbar sympathectomy was conducted to determine irrigraphic parameters possessing possible predictive value for the indication of sympathectomy. The value of the Index 6 (distal irrigation index) must be certainly taken into account; the Index 1 (proximal index) appears to be of interest when analyzing data with a view to sympathectomy in diffuse forms of arteritis. Three profile-types were distinguished; statistical analysis showed no significant difference in these profiles, with respect to the sympathectomy, in relation to the clinical results obtained. Irrigraphic modifications after sympathectomy were analyzed in 72 cases; results confirmed the improved efficacy of sympathectomy at Stage 2 than at Stages 3 and 4, but also showed that at Stage 2 the profile II appeared to react more favorably and that at Stages 3 and 4 the profile I appears to react less well than the other profiles. Also studied were patients with diabetes, who react less favorably to sympathectomy, patients who fail-to respond to sympathectomy, and those with worsening of irrigraphic profiles after sympathectomy, mainly in diabetics with profile I. These findings show that it is not possible to define a precise irrigraphic profile more favorable to sympathectomy, but that they provide interesting elements to be confronted with clinical and arteriographic data when deciding on the need for sympathectomy. PMID- 4031688 TI - [Predictive value of the reactive hyperemia test as an indicator for lumbar sympathectomy]. AB - Seventy-five patients had a lumbar sympathectomy for chronic arteritis of the lower limbs. This study was done to assess the predictive value of Hillestad's test (potential of vasodilatation) and that of the deep breath test (sympathic stimulation), realised by digital strain gauge plethysmography. Were considered a success the patients with claudication who doubled their walking distance and those with rest pain or gangrene who suffered no more or healed. Globally speaking, 49% were a success. A positive response to Hillestad's test was followed by an 83% overall success rate. For claudicants with femoropopliteal lesions the predictive success rate was 95% with a positive Hillestad's test, against 60% globally; for patients with rest pain or gangrene or with distal lesions the success probability was around 60% if Hillestad's test was positive. A negative response to Hillestad's test was always followed by a failure in diabetics. A better predictability ought to be obtained with the adjunction of a deep breath test. PMID- 4031689 TI - [Clinical results of lumbar sympathectomy as a function of the amplification factor of Hillestad's reactive hyperemia test. Apropos of a series of 72 cases of isolated lumbar sympathectomies]. AB - The efficacy of isolated lumbar sympathectomy was studied in 72 patients (36 with claudication, 36 with permanent ischemia) as a function of results of Hillestad's reactive hyperemia test (R.H.T.). Results were also assessed as a function of glucose tolerance, of the stage in Leriche and Fontaine's classification, of angiographic data, of certain pre-operative vascular function exploratory test parameters: systolic index at the ankle, digital pulsatility, segmental impedance plethysmography (irrigraphy), the tibial artery score and particularly the value for R.H.T. in the lower limb contralateral to the one for which sympathectomy was performed. Good results are very probable when the R.H.T. is positive or indifferent only in the lower limb for which sympathectomy is performed. Results were in fact better as the R.H.T. became more positive. Failure of treatment is very probable when the R.H.T. is indifferent in both lower limbs, particularly when the limb involved has an ankle systolic pressure lower than 0.25, an irrigraphic index lower than 0.10, the digital pulsatility has disappeared and the tibial artery score is 2/6 or less. PMID- 4031690 TI - [Study of the muscular perfusion of the lower limbs using thallium 201 scintigraphy before and after lumbar sympathectomy in 13 patients]. AB - Scintigraphy with 201-Thallium is a useful method for exploring muscle circulation in lower limbs of patients with arteritis. Comparative values with time can be obtained by studying respective isotopic activity ratios of the thigh, calf and foot. Unilateral isolated lumbar sympathectomy was performed in 13 patients for arteriopathy of the lower limbs (7 claudications, 4 isolated trophic disorders, 1 thrash-foot and 1 juvenile arteriopathy). Investigations included clinical and arteriographic explorations and functional tests (Doppler, distal pressure, digital plethysmography and 201-Thallium muscle scintigraphy) before and after operation. Pathology of the sympathetic chain was determined in each case. Short-term (2 weeks) follow up examinations gave data showing absence of correlation between the operative procedure and scintigraphy results. Muscle perfusion was improved in only 3 cases: one presented paradoxical improvement contralateral to the sympathectomy, while no change from the pre-operative values was recorded in 9 patients. The findings raise questions concerning the reproducibility of the scintigraphic method, and also confirm the pathogenic hypothesis by which lumbar sympathectomy has only a limited effect on muscle circulation. PMID- 4031691 TI - [The indications for lumbar sympathectomy as a function of clinical findings and of the results of the angiographic test]. AB - Indications for lumbar sympathectomy are presented as a function of the clinical findings and results of angiography, voluntarily ignoring data from non-invasive vascular function tests, in an attempt to answer two questions. Firstly, can the decision to perform lumbar sympathectomy depend on clinical findings only in 1983? Secondly, is angiography essential in all cases before sympathectomy? The positive response to both questions is based on a study of approximately 2,300 case reports. PMID- 4031692 TI - Biased intrachromosomal gene conversion in a chromosome lineage. AB - A model for the evolution of a family of tandemly repeated genes in a single chromosome lineage under intrachromosomal gene conversion [43] is analyzed further and extended. Direct and diffusion approximations are derived for the exact fixation probabilities, mean time to fixation or loss, and mean conditional fixation time of Nagylaki and Petes [43]. The distribution of the number of variant repeats under the joint action of gene conversion and reversible mutation is investigated; exact and approximate expressions are derived for the stationary distribution. It is shown that conversional bias greatly increases the amount of sequence homogeneity at equilibrium. The diffusion processes studied here also apply to selection and mutation in a finite population, and some new results are established for that classical problem. PMID- 4031693 TI - Carrier facilitated diffusion. AB - The concept of a mobile carrier combining reversibly with a substrate is considered as a possible mechanism for facilitated transport across biological membranes. The mathematical model is a system of three reaction diffusion equations with certain boundary conditions. Two limiting cases are discussed in detail: The case of a "thin" membrane where the diffusion of bound and unbound carrier from one surface to the other may be simulated by a single jump. If the diffusion rate of the substance to be transported is small, then an approximate stationary solution is derived using singular perturbation theory. Finally, the results of numerical simulations are presented for a wide range of parameters. PMID- 4031694 TI - Eye movements and the enhancement of edges. AB - A mathematical examination of retinal photochemistry leads to a hypothesis for Mach band phenomena based on eye movements. This retinal model suggests why minimally distinct borders fade under eye fixation and agrees qualitatively with subjective measures of border contrast as a function of overall field luminance. PMID- 4031695 TI - Permanent coexistence in general models of three interacting species. AB - We address the question of the long term coexistence of three interacting species whose dynamics are governed by the ordinary differential equations xi = xifi(i = 1,2,3). In order for any theory in this area to be useful in practice, it must utilize as little information as possible concerning the forms of the fi, in view of the great difficulty of determining these experimentally. Here we obtain, under rather general conditions on the equations, a criterion for judging whether the species will coexist in a biologically realistic manner. This criterion depends only on the behaviour near the one or two species equilibria of the two dimensional subsystems, the behaviour there being relatively easy to examine experimentally. We show that with the exception of one class of cases, which is a generalization of a classical example of May and Leonard [21], invasibility at each such equilibrium suitably interpreted is both necessary and sufficient for a strong form of coexistence to hold. In the exceptional case, a single additional condition at the equilibria is enough to ensure coexistence. PMID- 4031696 TI - Dimension reduction projection and our perception of evolution. AB - The evolution of a species can be viewed as a trajectory in multidimensional space. What we perceive is only a low dimensional projection from the total dimensionality necessary to fully describe a species. Motivated by the phenomenon of punctuated equilibria, it is shown that there are projections of gradualistic evolution which will have a punctuated character. However, whether our eyes and minds would choose such a projection of the total phenotype is not resolved. PMID- 4031697 TI - The early growth of cancer. AB - In this paper, we compare two types of stochastic models for the initial growth of cancerous tumors. In one type, the random element enters via the initial time of growth or via the initial size of the growth clone. In the other type, tumors differ from one another essentially via their growth rates. We present a simple test to distinguish between the two types when tumor size distributions are available from several time points. Size distributions are the key elements of such kinetic analysis given the limitation that an individual tumor can be measured only once, at the time of sacrifice of an experimental animal. We discuss these concepts in connection with data from particular experiments on carcinogenic growth in the livers of mice. PMID- 4031698 TI - Multiple stable recurrent outbreaks and predictability in seasonally forced nonlinear epidemic models. AB - A seasonally forced nonlinear SEIR epidemic model is used to simulate small and large amplitude periodic outbreaks. The model is shown to exhibit bistable behavior for a fixed set of parameters. Basins of attraction for each recurrent outbreak are computed, and it is shown that the basins of two coexisting stable outbreaks are intertwined in a complicated manner. The effect of such a basin structure is shown to result in an obstruction in predicting asymptotically the type of outbreak given an uncertainty in the initial population of susceptibles and infectives. PMID- 4031699 TI - Generalized stable population theory. AB - In generalizing stable population theory we give sufficient, then necessary conditions under which a population subject to time dependent vital rates reaches an asymptotic stable exponential equilibrium (as if mortality and fertility were constant). If chi 0 (t) is the positive solution of the characteristic equation associated with the linear birth process at time t, then rapid convergence of chi 0 (t) to chi 0 and convergence of mortality rates produce a stable exponential equilibrium with asymptotic growth rate chi 0-1. Convergence of chi 0 (t) to chi 0 and convergence of mortality rates are necessary. Therefore the two sets of conditions are very close. Various implications of these results are discussed and a conjecture is made in the continuous case. PMID- 4031700 TI - Heat stress in athletes. PMID- 4031701 TI - Screening high school athletes. PMID- 4031703 TI - Diagnosis of subarachnoid hemorrhage. PMID- 4031702 TI - Pruritic urticarial papules and plaques of pregnancy. PMID- 4031704 TI - Post-polio syndrome. PMID- 4031706 TI - Time for rewording "annual". PMID- 4031705 TI - A sense of the future. PMID- 4031707 TI - Influenza surveillance at Siriraj Hospital: 1979-1983. PMID- 4031708 TI - Asbestos bodies in randomised autopsy lungs in Thailand. PMID- 4031709 TI - Mullerian duct anomalies and unilateral renal agenesis: report of 21 cases from Ramathibodi Hospital. PMID- 4031711 TI - Smoking among medical students. PMID- 4031710 TI - Acute myocardial infarction in the young. PMID- 4031712 TI - Tuberculin reaction in Thai infants after BCG vaccination at birth. PMID- 4031713 TI - Erythropoietic protoporphyria: a first case report in Thailand and family study. PMID- 4031714 TI - Hamartoma of the tongue. PMID- 4031715 TI - Bacterial tracheitis, a case report. PMID- 4031716 TI - Prospective study of adverse drug reactions of antihypertensive drugs in Thai outpatients. PMID- 4031717 TI - The reversal of female sterilization by microsurgery: experiences with first 50 cases. PMID- 4031718 TI - Pharyngeal colonization by gram-negative bacilli in ambulatory diabetics. PMID- 4031719 TI - The hemoglobinopathies in iron deficiency patients. PMID- 4031720 TI - False reactive nonstress tests in postterm pregnancies. PMID- 4031721 TI - Calcified uriniferous perirenal pseudocyst: a case report. PMID- 4031722 TI - Papillary and glandular meningiomas: report of two cases. PMID- 4031723 TI - Electrocardiographic estimate of peak systolic pressure gradient in children with aortic stenosis. AB - In children with congenital aortic stenosis a modified mapping system was created to explore the electrocardiographic potentials on the chest surface from the left sternal edge (direct anterior), left axillary line (direct lateral) and midchest (45 degrees anterior to the lateral lead) in the third through the seventh intercostal spaces. Potentials were normalized according to chest size based on elliptical and cylindrical models of the chest with the heart at the center. The unadjusted and adjusted potentials were correlated with the peak systolic gradients across the left ventricular outflow tract and equations to predict the gradients were derived by stepwise multiple regression analysis. The best equation was: Gradient = -15.0 +(3.845 X MCT 4) +(0.474 X CD X LSS 3) + (0.138 X CD X MCS 3) where MCT 4 = T wave amplitude in the lead in the fourth interspace in the midclavicular line CD = AP chest diameter in cm LSS 3 = S wave amplitude in the lead in the third interspace at the left sternal border MCS 3 = S wave amplitude in the lead in the third interspace in the midclavicular line (R = 0.84, SEE = 24.3) There are areas on the chest surface that are unexplored by standard electrocardiography. The electrocardiographic potentials from these areas, when normalized for chest size, yield better estimates of transaortic gradients than previous estimates from the routine electrocardiogram. PMID- 4031724 TI - Localization of cardiac ectopic activity in man by a single moving dipole. Comparison of different computation techniques. AB - The accuracy of different computation techniques for the non-invasive localization of cardiac ectopic activity was evaluated. Body surface potentials were recorded from 63 leads in 14 patients with implanted pacemakers. The location, orientation and magnitude of a single moving dipole (SMD) were computed from the first eight terms of a truncated multipole expansion estimated from the body surface potentials. The SMD trajectories obtained during the QRS complex were plotted along with the heart outlines and pacing leads obtained independently from chest x-rays. The origin of the SMD trajectories was compared to the position of the pacing lead to evaluate the accuracy of the SMD. The optimum computation technique used a least-squares (LS) estimation of the multipole expansion truncated at 15 multipoles, in conjunction with a torso model that included regions of lower conductivity representing the lungs. With this method, the SMD trajectories originated near the pacing lead (25 +/- 12 mm) and adequately represented the progression of the ectopic wavefront across the entire heart silhouette. With the LS techniques using 8 or 24 multipoles, the spans of the trajectories were respectively too short, or too long to cover the heart, and the average distance between the SMD at QRS onset and the pacing lead was larger. With a surface integration technique, the SMD-pacing lead distances were similar, both for a finite homogeneous torso model with a fixed geometry, as well as for torso models adapted to the torso geometry of each patient. The SMD was found adequate to represent the progression of an ectopic wavefront, and to localize its origin in man. PMID- 4031725 TI - Effects of tachycardia with normal and ectopic ventricular activation on S-T segment potential and patterns in the dog. AB - Tachycardia induced by atrial pacing in the dog increases the intensity of potentials recorded on the body surface during the ST-T interval. The effects of tachycardia caused by ectopic right or left ventricular stimulation on ventricular recovery potentials were studied in 30 dogs. Rate was increased in a stopwise manner from 90 to 250 beats per minute by atrial pacing (ten dogs), or by left atrial-right ventricular sequential pacing (ten dogs), or by left atrial left ventricular sequential pacing (ten dogs). ECG effects were determined by construction of body surface isopotential maps from voltages registered from 84 torso electrodes using a P-R segment baseline. Ectopic stimulation intensified the repolarization maximum and shifted its location to correspond with sites of epicardial stimulation. These findings reflect a reduced cancellation of transventricular differences in recovery times, with earliest recovery occurring at earliest activated sites. Increasing rate with any one activation pattern linearly increased potential extrema magnitudes without further changes of spatial features. This singular response to tachycardia regardless of activation sequence is consistent with an increase in the apparent moment of a repolarization dipole without alteration of its orientation. PMID- 4031726 TI - P-wave changes in obstructive and restrictive lung diseases. AB - To evaluate the P wave changes in the electrocardiogram (ECG) in chronic lung diseases, we examined ECGs from twenty patients with interstitial pulmonary fibrosis (the FLD group) and twenty patients with chronic obstructive lung disease (fifteen with pulmonary emphysema and five with bronchial asthma, the COLD group). In the COLD group, the amplitude of P waves in leads II and III increased and the axis of the P wave shifted rightward. In the FLD group, however, these changes were not observed. Furthermore, the axis of the P wave exceeded +70 degrees in all the patients in the COLD group, and was less than +70 degrees for all the patients in the FLD group. The increased P wave terminal force in lead V1 was found in nine patients (45%) of the FLD group and in ten patients (50%) in the COLD group. We concluded that the rightward shift of the axis of the P wave was a characteristic of obstructive lung disease and that it was mainly caused by the overinflation of the lung. This P wave change was not observed in interstitial pulmonary fibrosis. PMID- 4031727 TI - Normal variations in body surface electrocardiographic potential distributions during QRS: effects of exercise and exercise training. AB - Total body surface electrocardiographic potential distributions, oxygen uptake (VO2), blood pressure and heart rate were monitored during maximal exercise procedures performed by 26 normal adult subjects (male and female) covering a range from sedentary to fit. Normal variations in the exercise response of the ECG during QRS were found not to be related to variations in the level of cardiovascular fitness as quantified by maximal VO2 or to variations in maximal heart rate and blood pressure. In a second experiment, seven sedentary adult female subjects underwent an exercise training protocol for ten weeks. Maximal exercise tests were performed before and after the training period. Exercise induced changes in the ECG during QRS were not affected by the physical training. We conclude that normal variations in the exercise response of the ECG during QRS are not related to the level of cardiovascular fitness of the subject. PMID- 4031728 TI - Evaluation of transthoracic countershock with initial energy levels up to 200 J in a coronary care unit. AB - In a five year prospective study, transthoracic countershock of patients in the coronary care unit was evaluated with respect to efficacy, transthoracic resistance and arrhythmias. Those patients dying within 12 hours of the recorded event are referred to as agonal patients. Atrial arrhythmias were generally first treated with quinidine or disopyramide and/or a digitalis preparation. Patients with coronary heart disease were treated with lidocaine, disopyramide, or verapamil when there was time for appropriate diagnosis. The efficacy of the first shock with an energy level between 50 J and 200 J in non-agonal patients was: for atrial fibrillation, 44% (N = 34), and between 83% and 93% for tachycardias and ventricular fibrillation. The cumulative efficacy of two shocks with energy levels between 50 J and 200 J was: in atrial fibrillation 53% and others between 90% and 96%. In agonal patients with ventricular fibrillation and acute myocardial infarction the efficacy of one shock of 100-150 J was 39% and two shocks of 100-200 J, 69% (N = 13). No correlation was found between the transthoracic resistance and parameters such as body-weight, length or thorax circumference, indicating that these should not be taken into account in the choice of the energy level for countershock. In non-agonal patients without coronary heart disease arrhythmias due to countershock increased in duration when the energy of the countershock increased (p less than 0.01, N = 39). It is concluded that the initial stored energy for defibrillation and cardioversion of nonagonal patients in a coronary care unit may be limited to 200 J (160 J delivered energy), even with atrial fibrillation after drug therapy in which case an initial energy level of 200 J seems more appropriate. PMID- 4031730 TI - Holter ECG study of the electrocardiographic phenomena in Prinzmetal angina attacks with emphasis on the study of ventricular arrhythmias. AB - The ECG phenomena in 20 outpatients (121 episodes) suffering from variant angina with transient ST segment elevation greater than 1.5 mm. (Prinzmetal angina) were studied by Holter monitoring. The most important changes in the ECG morphology were: a) increased height of the R wave in all cases, b) the S wave decreased or disappeared, c) the ST segment elevation varied from 1.5 to 38 mm, d) the TQ interval was ascending in 78 episodes, e) there was a double alternance of ST-TQ in 20 episodes and f) the first modification of the ECG was an increase of the T wave height. Arrhythmias were seen in 19 patients (44 episodes). The most frequent were premature ventricular contractions. The prevalence and importance of the ventricular arrhythmias were statistically related to the duration of the episodes (p less than 0.005), the degree of the ST segment elevation (p less than 0.005), the presence of ST-TQ alternance (p less than 0.005) and the presence of increased R wave greater than 25% (p less than 0.025). PMID- 4031729 TI - Sinus node echoes and concealed concealed conduction: additional sinus node phenomena confirmed in man by direct sinus node electrography. AB - Direct sinus node electrography has been previously used to assess several aspects of sinus node physiology: sinus node pauses, overdrive suppression, sinoatrial entrance block. This report presents data in which sinus node electrograms confirm two additional physiologic phenomena in man: concealed conduction in the sinoatrial junction and sinus node reentry. These findings verify the presence of previously suspected phenomena by careful deductive analysis of electrocardiographic and electrographic tracings. PMID- 4031731 TI - Epicardial isopotential mapping from body surface isopotential mapping in myocardial infarction. AB - It is useful to construct the epicardial isopotential mapping (the Ep Map) from the body surface isopotential mapping (the Body Map) for clinical diagnosis of cardiac disease, even though there are many unsolved problems in using the inverse solution. Yamashita et al. carried out this solution by using the finite element technique. In the present study, the clinical value of that method has been investigated in cases of myocardial infarction. The Ep Maps at 20, 25 and 30 msec. from the beginning of the QRS complex were obtained from the Body Map at the same time by using that method; the infarcted areas on the Ep Map were determined by using Toyama's method which was reported in a previous study. The infarcted area at 30 msec. on the Ep Map was located at the anterior wall along the ventricular septum in anterior infarction and at the posterior wall of the left ventricle in inferoposterior infarction. Patients were independently examined with the scintigram with thallium-201 and the infarcted area was coincident to the location of the abnormal findings of the scintigram. Moreover, the size of the infarcted area on the Ep Map and the size of the abnormal findings of the scintigram were parallel in most cases except one. PMID- 4031732 TI - Effect of perfusion rate of cholinergic agonist on sinus node automaticity. AB - Recent evidence supports a complex relationship between pressure in the sinus node artery and heart rate. In addition, it has been suggested that acetylcholine effects vary depending upon the pressure at which the drug is injected. We examined the cardiac chronotropic responses to acetylcholine, delivered via the sinus node artery using a constant flow perfusion technique. Dogs were anesthetized with chloralose and prepared to record ECG, arterial pressure and bipolar electrograms from the sinus node, sulcus terminalis, right atrium, right ventricle and His bundle. The sinus node artery was catheterized, distribution verified and autologously perfused via the femoral artery. Both vagi and both stellate ganglia were transected. Analog data were processed by computer for each cycle length during perfusion with normal Tyrode solution or Tyrode solution containing acetylcholine. Perfusion of normal Tyrode solution (1-4ml/min) resulted in prolongation in cycle length which was greater at higher flow rates but rapidly dissipated at all flow rates. Beyond mechanically-induced bradycardia, acetylcholine initially prolonged cycle length but cycle length prolongation faded with time. Delivery of acetylcholine at higher flow rates resulted in significantly greater prolongation of cycle length. Cycle length always returned back toward control although perfusion of acetylcholine continued. Thus, responses to acetylcholine are influenced not only by drug concentration but also by the flow rate at which the drug is delivered. This suggests a coupling of mechanical and pharmacologic components of chronotropic influences at the sinus node. PMID- 4031733 TI - Amitriptyline-induced Torsade de Pointes. Successful therapy with atrial pacing. AB - The author reports a case of Torsade de Pointes secondary to Amitriptyline overdose in an attempted suicide. Mechanism of tachycardia and guidelines for treatment are reviewed. PMID- 4031734 TI - Formation of the notochord in living ascidian embryos. AB - The dynamic behaviour of cells during formation of the notochord in the ascidian, Ciona intestinalis, was examined by means of Differential Interference Contrast (DIC) microscopy and time-lapse videorecording. The initial rudiment is formed in part as a consequence of the pattern of mitotic divisions as the blastopore shifts posteriorly. Vertical and horizontal rearrangements produce an elongate rod of disc-shaped cells stacked end to end. Further elongation is accompanied by a cell shape change. Some cell growth or swelling is indicated to occur later in development, but this growth appears to contribute mostly to an increase in the diameter, and only insignificantly to the length of the notochord. Intracellular vacuoles that appear around 13 h after fertilization increase in size and fuse at about 16 h form intercellular ones. These in turn merge to form the central matrix core of the notochord at around 18 to 20 h. As the notochord elongates and cells change in shape, the basal surfaces bleb actively. This surface activity may be related to formation of the perinotochordal sheath. PMID- 4031735 TI - Paths taken sensory nerve fibres in aneural chick wing buds. AB - What constrains growing nerves to follow the paths they take during the development of peripheral nerve patterns? This paper examines two, related, topics concerning the pathways taken by sensory nerve fibres in the embryo chick wing: the constraints imposed on the nerves by limb tissues; and the timing of axon outgrowth. Sensory ganglia from 7-day-old chick embryos were grafted into younger host embryo wing buds which had been previously denervated. The resultant nerve patterns revealed that, first, nerve fibres could grow almost anywhere within the wing bud, with the exceptions of cartilage and a region just beneath the growing tip. Secondly, the younger the host wing bud at the time of grafting, the more likely the neurites were to form a thick fascicle which followed the limb's normal nerve pathways. The wing apparently does not impose a rigid restraint on nerves to grow only along certain routes; however, if a nerve fibre reaches a normal nerve pathway, it prefers to follow it. PMID- 4031736 TI - Trophectodermal carcinoma: mouse teratocarcinoma-derived tumour stem cells differentiating into trophoblastic and yolk sac elements. AB - The transplantable tumour line derived from a spontaneous ovarian murine teratocarcinoma (Fekete & Ferigno, 1952) was cloned and characterized using light and electron microscopic and immunohistochemical techniques. Grown in ascites, the tumour consisted predominantly of stem cells and a small number of differentiated derivatives. The stem cells expressed surface reactivity with antibody to SSEA-3 and Forssman antigen, alkaline phosphatase, focal cytoplasmic reactivity with antibody to SSEA-1, and varying amounts of cytoplasmic glycogen and 3 beta-hydroxysteroid dehydrogenase. Their cytoskeleton reacted with antibodies to keratin and vimentin. The differentiated derivatives formed approximately 5-15% of the total cell population in ascites and appeared either as giant cells or were characterized by their reactivity with antibodies to H-2 or alpha-foetoprotein or intracellular and pericellular laminin or high levels of 3 beta-hydroxysteroid dehydrogenase activity. Solid tumours produced from subcutaneously injected cells had a variegated appearance suggesting, that like the limited differentiation in the ascites, the stem cells can give rise to trophoblastic, as well as parietal and visceral yolk sac elements. On the basis of the presented data the tumour stem cells were considered as representing malignant equivalents of the common precursor of trophoblastic, visceral and parietal yolk sac cells most likely corresponding to trophectoderm. Accordingly, the tumour was designated as trophectodermal carcinoma. PMID- 4031737 TI - Pioneering and pathfinding by an identified neuron in the embryonic leech. AB - Numerous investigations of pathfinding by embryonic neurons, including many leech neurons, have demonstrated that pathfinding is precise. Neurons project the correct number of growth cones which grow to their target areas by making specific choices along the way. However, one leech mechanosensory neuron, the dorsal P (PD) neuron, is unusual in the sense that it initially projects an excessive number of growth cones. One of the growth cones will form the peripheral axon while the others are eliminated. This suggests that PD is one of the earliest neurons to project a peripheral axon, i.e., it may pioneer a peripheral nerve, and that it searches with its multiple growth cones for an external cue which can guide it to its target area. Examination of the early PD axon with light and electron microscopy reveals that it indeed is the first growth cone in its nerve and that it grows in contact with a large non-neuronal (DV) cell until it reaches its target area. The DV cell has a unique morphology and location: a large cell body with thin flat processes extending from the edge of the ganglion to the target area of the PD. It is also present with its unique morphology prior to axonal outgrowth by the PD neuron. These features suggest that the DV cell may be an attractive substrate and/or axonal guidance cue for the PD peripheral axon and therefore for the entire peripheral nerve. PMID- 4031738 TI - The distribution of the polarizing zone (ZPA) in the legbud of the chick embryo. AB - The stage-21 to 22 legbud polarizing zone (ZPA) was mapped by transplanting small blocks of posterior marginal mesenchyme preaxially into stage-20 to -22 chick wing buds and assessing the degree of duplication of the wing digital skeleton produced in the host. Blocks taken from the posterior flank, from the angle between posterior flank and the proximal base of the limb bud, and from the most anterior distal position chosen (under the AER), all had very low activity. Blocks taken from the posterior margin of the legbud, plus the next distal block under the posterior part of the AER, all had high activity. We consider that barrier and amputation results on wing and legbud, when interpreted in the light of maps of the ZPA in both limb buds, are consistent with the hypothesis that both leg and wing have their growth and anteroposterior axis of pattern formation controlled by the ZPA. PMID- 4031739 TI - Genetic identification of tissue of origin of cellular populations within the mouse placenta. AB - The mouse haemochorial placenta is a complex mixture of maternal cells and foetal trophectoderm and inner cell mass (ICM)-derived cells. The majority of the placental tissue is assumed to be trophoblast in origin but the exact extent and localization of the ICM and maternal contribution has not previously been determined. Using embryo transfer and reconstituted blastocyst techniques, combined with isozymal and in situ genetic markers, we have established that about 70% of the 13 to 15-day placenta is trophectoderm-derived, 30% is maternal in origin, and 4% develops from the ICM. Nearly all of the maternal contribution was confined to the spongiotrophoblast region and all of the ICM contribution was confined to the labyrinthine trophoblast region, where it formed the foetal blood capillaries and the endodermal sinuses. Using the same genetic markers, we showed that cell suspension techniques commonly used to produce 'trophoblast' cell preparations from placenta do not enrich for trophoblast, and, indeed, that collagenase, the preferred dissociation technique for cell viability, produced cell suspensions in which ICM and maternal cells were preferentially dissociated. No method for producing pure trophoblast populations has yet been found. Some unusually high ICM contributions to the placenta were found in reconstituted blastocyst experiments using ICMs isolated from early 3.5-day blastocysts, suggesting that these ICMs may have contributed to the trophectoderm layer of the blastocyst. These and other experiments suggest that the inner cell mass lineage may not be closed until some time after formation of the blastocyst. PMID- 4031740 TI - Cautery-induced colour patterns in Precis coenia (Lepidoptera: Nymphalidae). AB - Cautery of the dorsal hindwing in the butterfly, Precis coenia, induces the formation of a concentric colour pattern around the site of injury. The induced pattern is identical in pigmentation to the eyespots that normally develop on this wing surface. This response to cautery also occurs, though much less dramatically, on the ventral forewing. In addition to the peculiar response to cautery, the dorsal hindwing of Precis also develops a series of unique pattern aberrations in response to coldshock. These consist of irregular elongation of the anterior eyespot along the proximodistal axis of the wing. In the most dramatic aberrations the eyespot field covers the entire anterior half of the wing surface. An analysis is presented that attempts to reconcile the effects of cautery on the Precis hindwing with the very different morphological effects of cautery on the colour pattern of Ephestia kuhniella, described by Kuhn & Von Engelhardt. Computer simulations reveal that the finding presented in this paper, as well as the classical work on Ephestia, can both be explained by assuming that the site of cautery becomes a sink for one of the morphogens involved in colour pattern determination. The experimental findings furthermore indicate that minor perturbations of the wing epidermis can evoke the physiological conditions that attend normal eyespot determination. It is shown that this interpretation also helps to explain the unusual pattern modifications following coldshock. PMID- 4031741 TI - Transferrin in foetal and adult mouse tissues: synthesis, storage and secretion. AB - Transferrin is an important growth-promoting serum glycoprotein synthesized chiefly in the liver in adults. The transferrin found in the mouse foetus is thought to be wholly a product of the foetus itself and its synthesis starts at lest as early as the 7th day of gestation. The major sites of synthesis in mouse foetuses are the visceral yolk sac (VYS) and liver (Adamson, 1982). We now report that other murine foetal tissues synthesize readily detectable amounts, namely lung, spleen, spinal cord and rib cage. Very low levels are also synthesized by the brain, muscle and pancreas. We can detect no synthesis of transferrin in late foetal thymus, heart or skin although mid-gestation foetal skin may make a very small amount. No synthesis of transferrin can be detected in adult brain, lung and spleen, but approximately equal rates of synthesis are detected in adult liver and adult ear pinna. Transferrin is accumulated by foetal and adult tissues in widely varying amounts and these have been measured by enzyme-linked immunosorbent assays of extracts. In addition to VYS and liver, high levels of transferrin are found in foetal skin, lung and rib cage with lower amounts in spinal cord, spleen and muscle tissues. Tissues of the 15th day foetus accumulate the highest concentrations of transferrin. A role for the mediation of transferrin in the stimulation of growth and differentiation by interaction tissues is discussed. PMID- 4031742 TI - Stimulation of division in mouse 3T3 cells by coculture with embryonic chick limb tissue. AB - Two regions of the chick limb bud--the apical ectodermal ridge and the zone of polarizing activity--have been shown to influence cell division and pattern formation during normal development and following surgical manipulation. In this study, using a simple coculture system, together with autoradiography, we have shown that these morphogenetically active regions of the limb bud can stimulate quiescent 3T3 cells to initiate DNA synthesis to a significantly greater degree than comparable but morphogenetically inactive regions of the limb bud. PMID- 4031743 TI - Development of synapses between identified sensory neurones and giant interneurones in the cockroach Periplaneta americana. AB - The cercal afferent, giant interneurone pathway in Periplaneta americana was used as a model for synapse formation. The morphology of the two identified filiform hair sensory neurones (FHSNs) and of two giant interneurones (GI2 and GI3) was followed throughout embryogenesis by cobalt injection. The FHSN axons enter the CNS at the 45% stage of embryogenesis, branch at 50% and form complete arborizations by 70%. The giant interneurones send out a primary dendrite at 45%. Secondary branches form between 50% and 60% and elaboration of the branching pattern takes place until 80% embryogenesis. At early stages the FHSN axons are within filopodial range of GI dendrites which may use these sensory processes as guidance cues. Synapse formation between the main FHSN axon shafts and GI dendrites was investigated by injection of the latter with HRP. From 55% to 65% the process is initiated by desmosome-like filopodial contacts, with subsequent vesicle clustering and formation of a small synaptic density. Numbers of contacts did not significantly increase after about 70%, but the number of synapses doubled between 65% and 75%, with each GI process becoming postsynaptic to two FHSN synapses and the presynaptic densities lengthening to become bars. From 75% embryogenesis to hatching there is a further small increase in synaptic bar length. In the first instar GI3 is postsynaptic to both FHSN axons, whereas GI2 forms very few synapses with the axon of the lateral FHSN (LFHSN). This imbalance of contacts is present throughout synaptogenesis, apart from some early filopodial contacts. GI3 forms synapses with the lateral side of the LFHSN axon from 60% embryogenesis but these are totally absent at hatching. The growth of glia along this side of the axon during the last 30% of development appears to be associated with degeneration of synapses in this region. Thus, as the dendrites of the GIs grow to form a miniature version of the adult without loss of branches, there is little evidence of an initial overproduction of FHSN-GI synapses. Similarly there is no evidence that GI2 forms 'incorrect' synapses with the axon of LFHSN. However, GI3 contacts are removed from an inappropriate region of a correct synaptic partner, LFHSN. PMID- 4031744 TI - Comparative effects of cathepsin inhibitors on rat embryonic development in vitro. Evidence that cathepsin D is unimportant in the proteolytic function of yolk sac. AB - The effects of two proteinase inhibitors, leupeptin and pepstatin on the development of 9.5-day rat conceptuses in vitro has been studied. All cultures were of 48 h duration and the inhibitors were present throughout the entire period. When pepstatin was added to the culture medium (5-25 micrograms/ml) conceptuses developed and grew to an extent that did not differ from untreated controls. However, leupeptin (1-4 micrograms/ml) caused severe growth retardation and abnormal development of conceptuses. The effects of the two inhibitors on the hydrolysis of 125I-labelled BSA and haemoglobin by homogenates of 10.5-day yolk sac indicated the biochemical basis for the differential toxic effects of the two inhibitors on development. Leupeptin was highly inhibitory of the degration of both substrates whereas pepstatin caused no inhibition of 125I-labelled BSA hydrolysis, and only a slight inhibition of haemoglobin hydrolysis. These observations demonstrate that cathepsin D, a lysosomal aspartic proteinase that is specifically inhibited by pepstatin is not involved in yolk-sac-mediated protein utilization by early organogenesis-phase conceptuses and that lysosomal cysteine proteinases, specifically inhibited by leupeptin, are of paramount importance in this yolk sac function. PMID- 4031745 TI - Regeneration of axolotl hindlimbs bearing surgically created discontinuities in the anterior-posterior axis. AB - The pattern regulation process in amphibian limbs has been examined with respect to the presence of discontinuities in the anterior-posterior (a-p) axis. Limbs bearing such discontinuities were surgically created by contralateral exchange of either dorsal or ventral half thighs and these limbs were then amputated immediately after surgery. The results demonstrate that a-p discontinuities lead to the formation of extra limb structures during distal outgrowth in contrast to the mosaic behaviour of comparable limb stumps which contain dorsal-ventral (d-v) discontinuities (Holder & Weekes, 1984). It is evident, therefore, that pattern regulation in the transverse limb axes is accomplished by basically different mechanisms. The structure of the limbs in the present study was examined in Victoria-blue-stained wholemounts and serial sections. The results allow some discussion of the basic mechanisms for pattern regulation in the two transverse limb axes and the relationship between them. PMID- 4031746 TI - Developmental variability within and between mouse expanding blastocysts and their ICMs. AB - We have attempted to reduce the developmental heterogeneity amongst populations of mouse blastocysts by synchronizing embryos to the first visible signs of blastocoel formation. Using embryos timed in this way, we have examined the extent of variation of inside and outside cell number and of inside cell size, nuclear DNA content and developmental potential, between and within embryos of a similar age postcavitation. The overall impression gained is one of wide heterogeneity in inside:outside cell number ratios and in cell cycling and its relation to cavitation among embryos of similar age postcavitation. However, the simplest explanation of our results suggests that cavitation generally begins at a time when most outside cells are in their sixth developmental cell cycle and that outside cells, as a population, are a little ahead of inside cells in their cell cycling. Additionally we present evidence that, within at least some individual inner cell masses (ICM), there is intraembryo variation in the time at which inside cell developmental potential becomes restricted. PMID- 4031747 TI - In vitro analysis of interactions between sensory neurons and skin: evidence for selective innervation of dermis and epidermis. AB - Axons from dorsal root ganglion cells cultured in a serum-free medium on poly-L lysine or collagen substrates interact differently with dermis and epidermis. The orientation of neurite growth is not changed by encountering mesenchymal cells migrating from the outgrowth zone of a dermal explant, and neurites form close membrane associations with some dermal cells; in contrast, neurites strongly avoid epidermis and deviate around the edge of an epidermal explant. When cultures are grown on polylysine this avoidance behaviour occurs at a distance from the epidermis. It is suppressed in the presence of necrotic epidermal cells. We suggest that this avoidance is due to epidermal diffusible factor(s) which bind preferentially to polylysine. The possibility of an absence of specific recognition cues between neurites and epidermal cells is discussed. PMID- 4031749 TI - Polyneuronal innervation of an adult and embryonic lobster muscle. AB - Motor innervation of the deep extensor muscle in the abdomen of lobsters (Homarus americanus) was compared in adults and embryos using electrophysiological techniques. There is widespread innervation of the adult muscle by the common excitor and inhibitor axons and regionally restricted or private innervation by three more excitor axons. In the embryo the earliest sign of functional innervation revealed a single inhibitory and two to three excitatory axons thus denoting simultaneous innervation by the full complement of axons. In corroboration, serial-section electron microscopy revealed several axon profiles invading the embryonic deep extensor muscles and giving rise to well-defined neuromuscular synapses with presynaptic dense bars. Innervation patterns to homologous regions of the embryonic and adult muscles were similar, consisting of a few large inhibitory synapses and many small excitatory ones. Consequently the adult pattern of polyneuronal innervation occurs simultaneously and in toto during embryonic development. PMID- 4031748 TI - Acetylcholinesterase (AChE) and pseudocholinesterase (BuChE) activity distribution pattern in early developing chick limbs. AB - The distribution of acetylcholinesterase (AChE) and pseudocholinesterase (BuChE) activities was studied by histochemical, quantitative and electrophoretical methods during the early development of chick limbs, from stage 16 to stage 32 H.H. (Hamburger & Hamilton, 1951). By quantitative methods, true AChE activity was found, and increased about threefold during the developmental period, together with a smaller amount of BuChE which increased more rapidly in comparison with the AChE activity from stage 25 to 32 H.H. Cholinesterase activity was histochemically localized mainly in interacting tissues, such as the ectoderm (including the apical ectodermal ridge) and the underlying mesenchyme. True AChE was histochemically localized around the nuclei and on the plasma membrane of ectodermal (including AER) and mesenchymal cells, and at the plasma membrane of mesenchymal cell processes reaching the basal lamina between the ectoderm and the mesenchyme. AChE together with BuChE activity was found in the basal lamina between the ectoderm and the mesenchyme, in underlying mesenchymal cells and in deeper mesenchymal cells, especially during their transformation into unexpressed chondrocytes. During limb morphogenesis, the cellular and regional localization of the enzyme activities showed variations depending on the stage of development and on the occurrence of interactions. The possibility of morphogenetic functions of the enzyme id discussed. PMID- 4031750 TI - Modulation of epidermal cell shaping and extracellular matrix during caudal fin morphogenesis in the zebra fish Brachydanio rerio. AB - Distinct changes in epidermal cell shaping largely define the overall pattern of growth and form during generation of the ectodermal ridge and early stages of fin fold morphogenesis. The epidermal portion of the ridge and early fin fold are formed from a strip of epidermal cells that is only six to nine cells wide. There is apparently no increase in the number of these cells during initial formation of the ridge and its subsequent conversion into a fin fold which contains extracellular matrix fibres. Epidermal cells adopt a wedge-shaped morphology during ridge production. Distinct changes in the shaping and contact relationships between basal portions of these cells generate intercellular spaces at several discrete loci within the ridge. These spaces become continuous with each other to form a subepidermal space. Hence, the subepidermal space is not produced by straight-forward folding of an epidermal sheet. Cells flanking the sides of the ridge start to flatten as it is converted into a fin fold. A continuous row of distinctive cells is positioned along the apex of the developing fold. The term 'cleft cells' is suggested for these apical cells. Each cleft cell retains a wedge-shaped form during fold formation and develops a basal cleft-shaped invagination. Invaginations are aligned in neighbouring cleft cells so that these cells cap the distal boundary of the subepidermal space where collagenous extracellular fibres called actinotrichia run anteroposteriorly along the length of the fin fold. This orientation is in direct contrast to the proximodistal orientation of actinotrichia within the remainder of the subepidermal space. During early stages of fold production a temporary set of previously unreported extracellular cross fibres spans the subepidermal space at right angles to actinotrichia. These configurations of extracellular fibres could be advantageous for maintaining the structural integrity of the early fin fold. PMID- 4031751 TI - Maps of strength of positional signalling activity in the developing chick wing bud. AB - Tissue from the posterior margin of the developing limb bud, when grafted to the anterior margin, evokes the formation of a mirror-image limb duplication from the host tissue. We present maps of the spatial and temporal distribution of this signalling activity in the chick wing bud based on a bioassay that provides a quantitative measure of the completeness of the additional structures (the strength of activity index). Activity is first detected prior to the initial appearance of the limb primordium as early as Hamburger & Hamilton stage 14. It reaches a maximum during early outgrowth of the bud at stages 19 to 25. It then declines as the limb starts to differentiate into its final morphological pattern. The design of the experiment provides serendipitous data showing that two operators can consistently perform grafts with high reproducibility between them while variability between embryos is somewhat higher. The maps of activity are of particular practical value in precisely defining for the experimental embryologist and molecular biologist those positions and stages at which peak signalling activity resides. PMID- 4031752 TI - Sequence and regulation of morphological and molecular events during the first cell cycle of mouse embryogenesis. AB - Mouse oocytes were fertilized in vitro and the precise timing and sequence of morphological and molecular events occurring during the first cell cycle were investigated. The timing of development through the first cell cycle was found to be initiated by an event associated with sperm penetration rather than with germinal vesicle breakdown. DNA replication is initiated randomly in either pronucleus of a given egg, beginning approximately 11 h post insemination (hpi), and S phase lasting 6-7 h in both. Careful study of polypeptide synthetic profiles revealed three classes of changes in polypeptide synthesis during the first few hours of development: fertilization-independent, fertilization accelerated, and fertilization-dependent. Pulse-chase experiments and in vitro translation of extracted mRNA showed that the changes in polypeptide synthetic profile result from differential mRNA activation, differential polypeptide turnover and post-translational modifications. These results support the notion that following ovulation, development is controlled at two levels. An endogenous (oocyte) programme, set in train by the terminal events of oocyte maturation, may regulate the 'housekeeping' functions of the egg, while sperm penetration activates a further endogenous (fertilization) programme, which may serve to initiate subsequent embryogenesis. PMID- 4031753 TI - pH affects fruiting and slug orientation in Dictyostelium discoideum. AB - We have demonstrated two interesting facts about the transition from the migration stage to the final fruiting stage of Dictyostelium discoideum. One is that fruiting is favoured on acid substrata, and secondly, migrating slugs tend to migrate towards the acid side of a pH gradient. The suggestion is offered that these results can be interpreted in terms of the effects of NH3. It appears to be an additional mechanism (besides phototaxis and thermotaxis) to assure that the final fruiting takes place in a favourable environment. PMID- 4031754 TI - The ontogenesis of cranial neuromeres in the rat embryo. I. A scanning electron microscope and kinetic study. AB - The development of the cranial neuromeres, rostral to the level of the first somite, in rat embryos during neurulation is described. Examination of scanning electron micrographs of 4-, 8-, 12- and 16-somite-stage embryos has shown that the neuromeres develop in a strictly ordered pattern but the sequence is not ordered in either a rostrocaudal or caudorostral direction. The two mesomeres are shown to develop by subdivision of a previously formed mesomere, whilst the rhombomeres develop independently of each other. At the completion of cranial neurulation two mesomeres and nine rhombomeres (including the preotic sulcus) but no prosomeres are identifiable. A direct correlation of the position of peaks in mitotic index along the embryonic axis with the position of sulci on the surface of the neural epithelium, was not possible. However, it is suggested that the mitotic index peak is the initial means of identifying a neuromere, and once the neuromere is expressed morphologically as a surface sulcus the mitotic index returns to its basal level. PMID- 4031755 TI - An allelic difference determines reciprocal patterns of expression of binding sites for Dolichos biflorus lectin in inbred strains of mice. AB - We used staining of tissue sections by lectin conjugates to screen inbred strains of mice for polymorphisms which could be used as histological markers of chimaerism. We found one polymorphism, which involves reciprocal patterns of expression of binding sites for the N-acetyl-galactosamine-binding lectins from Dolichos biflorus (DBA), Helix pomatia (HPA) and Wisteria floribunda (WFA) on intestinal epithelium and vascular endothelium. The polymorphism is due to alleles at a single locus, designated D1b-1 (for Dolichos lectin binding). Of 29 inbred strains examined, 3 are D1b-1a (type strain RIII-ro; gut epithelium-ve, vascular endothelium + ve), and 26 are D1b-1b (type strain C57BL/6J; gut epithelium + ve, vascular endothelium-ve). In RIII-ro and C57BL/6J embryos, the polymorphic difference is not clearly present until day 11 of gestation. Before then, embryos of both strains express binding sites on gut epithelium and on endothelium. The temporal and tissue-specific patterns of expression of lectin binding sites may result from differences in expression of an N-acetyl galactosaminosyl transferase. If so, elucidation of the genetic basis of the polymorphism might provide an insight into the mechanisms of developmental regulation of glycosyltransferase activity. PMID- 4031756 TI - Adhesiveness of mouse primordial germ cells to follicular and Sertoli cell monolayers. AB - The adhesiveness of female and male mouse primordial germ cells (PGCs) to somatic cell monolayers of various origin has been studied in the definite conditions of an in vitro system. PGCs were isolated from the gonads of embryos of various post coital ages according to the method of De Felici & McLaren (1982), and seeded on the cell monolayers. PGCs from 12.5 to 15.5 days post coitum (dpc) embryos specifically adhered to Sertoli and follicular cells obtained from adult gonads. The percentage of female PGCs which adhered to follicular cell monolayers was significantly higher than that of male PGCs. No significant adhesion was seen between PGCs and somatic cell monolayers obtained from various embryonic and adult tissues. The results obtained indicate that the simple in vitro assay described in the present paper might help to characterize the cellular interactions between somatic and germ cells during gonadal development. PMID- 4031758 TI - Design and performance of muscular systems. Based on papers presented at the Seventh International Conference on Comparative Physiology. Crans-sur-Sierre, June 1984. PMID- 4031757 TI - Muscle function: a personal view. PMID- 4031759 TI - Matching of muscle properties and motoneurone firing patterns during early stages of development. AB - In adults, muscle fibres match the functional requirements of the motoneurone that supplies them. During early stages of postnatal development of the rat neither muscle fibre properties, nor activity patterns of motoneurones supplying fast and slow muscles have completed their differentiation. Nevertheless, even at this early stage of development the muscles have characteristic properties that are well matched to the activity patterns of immature motoneurones. With further development differentiation of motoneurone activity and muscle fibre properties goes hand in hand. If during this period of linked differentiation, connections between the motoneurones and muscle fibres are disrupted, the development of fast muscles is permanently impaired. PMID- 4031760 TI - Control properties of motor units. AB - This review will deal with two evolving concepts which describe and attempt to unify various observations concerning the behaviour of motor units that have been reported during the past decade. The two concepts are: The common drive which describes the behaviour of the firing rates of motor units, and appears to provide a simple schema for controlling motor units; and the firing rate/recruitment interaction which appears to enhance the smoothness of the force output of a muscle. The evolution of these concepts has been expedited by the development of recent techniques such as our decomposition technique which enables us accurately to decompose the myoelectric signal into the constituent motor unit action potential trains. For details refer to LeFever & De Luca (1982), Mambrito & De Luca (1983) and Mambrito & De Luca (1984). PMID- 4031761 TI - Fuels and pathways as designed systems for support of muscle work. AB - Muscle in all animals relies upon four potential sources of energy: ATP hydrolysis, phosphagen hydrolysis, fermentations or oxidative metabolism. Although the relative contributions of different fuels varies greatly in different organisms, in none is there a simple reliance on stored ATP. Muscle work therefore requires a balance between rates of utilization and formation of ATP, a provision supplied by one of the three remaining fuels and metabolic pathways. Useful endogenous fuels must be storable at high level, and rapidly mobilizable with minimal perturbation of [ATP] and with minimal end-product effects on pH, charge or osmotic balance. In addition to displaying these properties, good exogenous fuels must be transferable at high rates between depot sites and muscle; actual flux rates of exogenous fuels depend upon respective ATP yields and are lowest for fuels which most amplify the yield of ATP per mol substrate oxidized. Substrate flux rates must be matched with O2 flux rates and with rates of endogenous substrate mobilization in order that the right energy yielding pathways are activated at the right times. Of various control possibilities, an effective competition for ADP (and possibly Pi) seems at this time to be the dominant strategy for assuring integration of aerobic and anaerobic ATP-yielding pathways. PMID- 4031762 TI - Patterns in mammalian muscle energetics. AB - A description of cellular energetics of muscular contraction is given in terms of the rates and extents of high-energy phosphate splitting during contractile activity, in terms of high-energy phosphate resynthesis by respiration and net anaerobic glycolysis, and in terms of the associated uptake and/or release of H+. These chemical changes have been studied quantitatively by rapid freeze-clamping methods and by 31P-NMR methods. The pattern of chemical changes in a fast-twitch glycolytic muscle is rapid depletion of phosphocreatine and later ATP levels, cellular acidification, and a much slower rate of resynthesis of high-energy phosphate compounds during the recovery period afterwards than occurs in the slow twitch oxidative muscles. In steady-state contractile activity below the maximal, graded levels of high-energy phosphates and of cellular respiration are achieved in both fast-twitch and slow-twitch muscles. Within the metabolic range up to the maximal aerobic capacity, which differs several-fold for different fibre types, this gradation is mediated by the creatine kinase reaction and phosphocreatine stores. Thus while the amount of enzyme present and the content of phosphocreatine differs among muscles of different types, the same general energetic function is seen to occur in all muscle cells. The creatine kinase reaction is both an energy reservoir and a buffer preventing large swings in the ATP/ADP ratios. PMID- 4031763 TI - Metabolic heterogeneity of muscle fibres. AB - Mammalian skeletal muscle is an extremely heterogeneous tissue. Its diversity results from a spectrum of fibres which are metabolically suited to a wide range of functional demands. As judged from enzyme activity analyses of single fibres, the metabolic properties of fibres belonging to the same motor unit are similar or identical. It is likely, therefore, that the phenotype expression of muscle fibres is primarily under neural control. Differences in recruitment patterns of various motor units explain the wide range of metabolic properties as evidenced by pronounced variations in enzyme activities and enzyme activity ratios. There exist large overlaps between the activity spectra of various enzymes of anaerobic and aerobic metabolism in slow- and fast-twitch fibres. Nevertheless, these two major fibre classes can be distinguished by discriminative enzyme activity ratios (e.g. phosphofructokinase/malate dehydrogenase, phosphofructokinase/3-hydroxyacyl CoA dehydrogenase, fructose-1,6-diphosphatase/phosphofructokinase). Moreover, slow-twitch fibres display an H-type isozyme pattern of lactate dehydrogenase, whereas fast-twitch fibres are characterized by a predominance of LDH-5. No clear cut differences exist between enzyme activity profiles and LDH isozyme patterns of the IIA and IIB subgroups of fast-twitch fibres. Comparative studies indicate that the metabolic properties of IIA and IIB fibres vary in different animal species. This observation supports the notion that metabolic and myosin-related properties of muscle fibres may be regulated independently. Due to relatively high turnover rates of enzymes of energy metabolism in muscle, changes in functional demands may be met by relatively rapid changes in metabolic properties. In view of these findings it is not surprising that muscle fibres display a spectrum of metabolic properties and represent stages within a dynamic equilibrium. PMID- 4031764 TI - Differences in metabolic potential of skeletal muscle fibres and their significance for metabolic control. AB - The role of an increase in oxidative potential of skeletal muscle in the enhanced work capacity and greater use of fat as a fuel after endurance training is discussed. Evidence is presented to illustrate that this adaptive response is probably expressed at the cellular level by a more rapid translocation into the mitochondria of the ADP generated during contractile activity. The consequence of this is a tighter control over the glycolytic process thereby creating more favourable conditions for the entry of acetyl units derived from beta-oxidation of fatty acids into the citric acid cycle. PMID- 4031765 TI - Metabolic indicators of fibre recruitment in mammalian muscles during locomotion. AB - Fast-twitch-oxidative-glycolytic (FOG), fast-twitch-glycolytic (FG) and slow twitch-oxidative (SO) fibres are distributed within and among physiological extensor muscles in mammals in predictable patterns. Deep muscles and the deep portions of extensor muscles are primarily composed of SO and FOG fibres, and the more peripheral portions of the muscles have higher concentrations of FG fibres. During terrestrial locomotion, the fibres are recruited in this same general order from postural standing through high speed running to jumping (i.e. during standing deep SO fibres are active and during locomotion there is a progressive peripheral recruitment of fibres from SO to FOG to FG). Several metabolic indicators may be used to map these fibre recruitment patterns, including glycogen loss in fibres, metabolic enzyme changes during training at different speeds, and distribution of blood flow within and among the muscles. Concerning the latter, during standing in rats blood flows in the hindlimb muscles are directly proportional to the SO fibre populations in the muscles. However, during locomotion the elevations in blood flow over pre-exercise are a function of the populations of FOG fibres in the muscles. Blood flows in the peripheral white portions (FG fibres) of extensor muscles are not significantly elevated until the rats run at high speeds, when the FG fibres presumably are recruited. During swimming, when flexor muscles are relatively more active than extensor muscles (as compared with terrestrial locomotion), blood flows in the flexors are correspondingly higher. Thus, there exists a clear 'biological economy' in the matching of blood flow to the specific fibres that are active within and among muscles during exercise. PMID- 4031766 TI - The maximum forces exerted by animals. AB - This paper reviews the maximum forces exerted by animals in a wide range of activities including running, jumping, swimming and biting. Most of the data refer to vertebrates and arthropods, ranging in size from 0.5-mg fleas to 3-tonne elephants. Maximum forces exerted on the environment give values of (force/body weight) which lie, in most cases, between 0.5 body mass-1/3 (kg) and 20 body mass 1/3. Maximum forces exerted by major muscle groups give values of (force/body weight) in most cases between 10 body mass-1/3 and 50 body mass-1/3. PMID- 4031767 TI - Sustained force development: specializations and variation among the vertebrates. AB - The kinds of muscle fibre that are recruited for sustained force production by different vertebrates are described. Although aerobic metabolism always accounts for a significant proportion of their ATP turnover, no single characteristic such as colour, number and form of motor endplates, membrane properties, myosin isotype or contraction speed is diagnostic of such muscles. As mechanical power output increases, there is a tendency for a decrease in fatigue resistance with repetitive usage and an increase in both aerobic capacity and the fraction of energy requirements derived from glycolysis. PMID- 4031768 TI - Force development during sustained locomotion: a determinant of gait, speed and metabolic power. AB - This paper develops three simple ideas about force development during sustained locomotion which provide some insights into the mechanisms that determine why animals change gait, how fast they can run, and how much metabolic energy they consume. The first idea is that the alternate stretch-shorten pattern of activity of the muscles involved in locomotion allows muscle-tendon units to function as springs, affecting the amount of force a given cross-sectional area of muscle develops, and the metabolic requirements of the muscles for force development. Animals select speeds and stride frequencies which optimize the performance of these springs. The second idea is that muscle stress (force/cross-sectional area) determines when animals change gait, how fast they run and their peak accelerations and decelerations. It is proposed that terrestrial birds and mammals develop similar muscle stresses under equivalent conditions (i.e. preferred speed within a gait) and that animals change gaits in order to reduce peak stresses as they increase speed. Finally, evidence is presented to support the idea that it is the time course of force development during locomotion, rather than the mechanical work that the muscles perform, that determines the metabolic cost of locomotion. PMID- 4031769 TI - The role of compliance in mammalian running gaits. AB - The running gaits used by both bipedal and quadrupedal animals are reviewed and contrasted. At high speeds, bipeds use both ordinary running, in which the legs move opposite one another, and hopping. Quadrupeds generally use the trot or its variations at moderate speeds, and first the canter and then the gallop as speed increases. Running in both bipeds and quadrupeds generally involves at least one aerial phase per stride cycle, but certain perturbations to running including running in circles, running under enhanced gravity, running on compliant surfaces and running with increased knee flexion (Groucho running) can reduce the aerial phase, even to zero. A conceptual model of running based on the idea that an animal rebounds from the ground like a resonant mass-spring system may be used to compare the various gaits. The model makes specific predictions which show that galloping is generally faster than cantering, pronking or trotting, and requires lower peak vertical forces on the legs while also giving a smoother ride. Even so, trotting might be preferred to galloping at low and moderate speeds for the same reason that normal running is preferred to Groucho running-the more compliant gait offers a smoother ride and lower vertical ground-reaction forces on the feet, but this can only be obtained at a high cost of increased metabolic power. PMID- 4031770 TI - Efficiency of vertebrate locomotory muscles. AB - We have examined the efficiency of vertebrate striated muscle at two different organizational levels: whole animals and isolated muscles. Terrestrial locomotion is used as a model of 'normal' muscular contraction; animal size and running speed are used as independent variables in order to change either the metabolic requirements of the muscles or the mechanical power production by the muscles over a wide range of values. The weight-specific metabolic power input to an animal increases nearly linearly with speed and increases with decreasing body size, while the weight-specific mechanical power output increases curvilinearly with speed and is independent of size. Consequently, the efficiency of the muscles in producing positive work increases with speed and the peak efficiency increases with increasing body size, attaining values of over 70% in large animals, but only 7% in small ones. The isolated muscle experiments were performed on frog muscle, and rat 'fast' and 'slow' muscles. We measured the work done, the oxygen consumed during recovery from the stimulation, and calculated the efficiency and the 'economy' (the cost of maintaining tension). The muscles were made to: (i) emulate the contractions seen during locomotion, i.e. shorten after a pre-stretch; or (ii) shorten at the same velocity and from the same muscle length as in (i), but without the pre-stretch. It was found that in mammalian muscles the peak efficiency with a pre-stretch attained high values, approaching the peak efficiencies in large animals. The maximum efficiency (attained at 1 length s-1 in fast muscle and at 0.5 lengths s-1 in slow muscle) did not differ much in the two muscles, whereas economy was greater in the slow muscle than in the fast muscle. PMID- 4031771 TI - Power and efficiency of insect flight muscle. AB - The efficiency and mechanical power output of insect flight muscle have been estimated from a study of hovering flight. The maximum power output, calculated from the muscle properties, is adequate for the aerodynamic power requirements. However, the power output is insufficient to oscillate the wing mass as well unless there is good elastic storage of the inertial energy, and this is consistent with reports of elastic components in the flight system. A comparison of the mechanical power output with the metabolic power input to the flight muscles suggests that the muscle efficiency is quite low: less than 10%. PMID- 4031773 TI - Metabolic and circulatory limitations to VO2 max at the whole animal level. AB - The O2 path from environment to mitochondria can be viewed as a cascade of resistances in series, each being overcome by a specific pressure gradient (O2 conductance equation). To assess the relative importance of the different factors that can set a limit to VO2 max, three sets of resistances will be identified, RQ, Rc and Rm, inversely proportional to: O2 transport (Qmax X [Hb]), RQ; capillary cross section, Rc; and succinic dehydrogenase (SDH) activity, Rm. Published data show that changes of VO2 max can be induced by altering the blood O2 capacity, or by training, and that these changes are accompanied by measured changes of the above identified resistances. From these data, the ratio of each resistance to the overall resistance can be calculated by algebraic manipulation of the O2 conductance equation, expressed in relative form. It can thus be shown that: in two-legged exercise, about 75% of VO2 max is set by O2 transport, the remaining fraction being about equally partitioned between the two peripheral factors indicated above, and that in one-legged exercise, the limits to VO2 max are about equally set by central and peripheral factors. PMID- 4031774 TI - Malleability of the system in overcoming limitations: functional elements. AB - Three different views can be found in the literature concerning the classical question in exercise physiology: what limits maximal oxygen uptake in man? Some authors believe that the limitation is the maximal rate of oxygen delivery by the cardiovascular system. Others argue that oxygen uptake is limited by the capillary bed or metabolic capacity of skeletal muscle, and the third line of thought is that no single factor can be found to be directly limiting as all links in the oxygen transport are so closely matched. The stand taken in this paper is that the skeletal muscle of man can be excluded as a limiting factor for maximal oxygen uptake in whole body exercise. It can be shown, by direct measurements, that in sedentary and in trained man maximal perfusion and oxygen utilization of skeletal muscle is so high that if all muscles in the body were engaged in intense exercise, the cardiac pump function would have to be 2-3 fold larger than it is. What happens in whole body exercise is that each muscle group receives only a fraction of the blood it can accommodate. The primary role for a larger capillary network observed in trained muscles is to keep or extend mean transit time. Elevated mitochondrial enzyme activities affect the metabolic response (i.e. lipid oxidation is elevated in trained muscles). However, these adaptations are not necessary for increasing the maximal oxygen uptake of man, as the capacity of the heart is limiting. Improved training techniques (which induce even larger improvements in cardiac pump function) may reveal that pulmonary diffusion capacity is the limiting factor. PMID- 4031772 TI - Metabolic and circulatory limitations to muscular performance at the organ level. AB - Within working muscle, development of conditions that directly influence exercise performance is dependent on many factors, including: intensity and duration of exercise, type of skeletal muscle fibres recruited, cardiovascular support to the working fibres and the inherent metabolic characteristics of the contracting fibres. In general, it is possible to identify factors that seem to alter exercise performance only at relatively intense exercise conditions. During prolonged moderately intense exercise (e.g. 70-80% maximal oxygen consumption for at least 60-90 min) decline in performance is related to the depletion of glycogen within the working muscle. Although the cause of muscle performance decline during very intense exercise is not known, an extreme acidosis is found, especially in fast-twitch muscle, which could significantly disrupt normal metabolic and contractile processes. During fatigue caused by intense contraction conditions, ATP content decreases (by approx. 50%) and there is a stoichiometric production of IMP and ammonia in fast-twitch muscle. This loss in adenine nucleotide content is dependent on the severity of the contraction conditions relative to the functional aerobic capacity of the muscle fibre, since fast twitch red (high mitochondria, high blood flow) and fast-twitch white (low mitochondria, low blood flow) muscles respond differently. In contrast, during similarly intense contraction conditions, rat slow-twitch muscle fibres maintain their ATP content and do not produce significant amounts of IMP. Indirect evidence suggests that a similar contrast between fibres occurs in humans during maximal exercise. Thus, there seems to be a fundamental difference between fast- and slow-twitch muscles in the management of their adenine nucleotide contents during intense contraction conditions. Whether this is related to the known differences in the fatigue process between these fibre types is not known. PMID- 4031775 TI - Malleability of skeletal muscle in overcoming limitations: structural elements. AB - The quantitative structural composition of skeletal muscle tissue shows a wide range of variability among different species of animals and in any one species among muscles with a different function. Moreover, experimental manipulations such as exercise training or chronic electrical stimulation can dramatically change the ultrastructural appearance of the muscles involved. Both in endurance exercise and in chronic electrical stimulation the volume density of mitochondria can be increased greatly (by more than three-fold in the stimulation experiments). This happens without an apparent change of the internal architecture of the mitochondria, since the surface density of the inner mitochondrial membranes remains constant. In situations where both the mitochondrial volume and the maximal rate of oxygen consumption of the muscle tissue are known, these two variables are found to be linearly related. It can be calculated that the 'maximal' oxygen consumption of a unit volume of mitochondria in muscle is close to 5 ml O2 min-1 cm-3 under comparable conditions in man, mouse and a series of African mammals. It is hypothesized that there is a constant volume of oxygen metabolized per unit volume of mitochondria and unit time under limiting conditions in working skeletal muscle tissue. Given the efficiency of muscular energy conversion, this would allow an estimate of the potential for aerobic power production of a muscle from measurement of its volume density of mitochondria. PMID- 4031776 TI - Malleability of the motor system: training for maximizing power output. AB - The training programmes used to improve the strength and/or endurance capacities of athletes are described. Specific stimuli are either high tension in contracting myofibrils or high turnover rates in the oxidative metabolism of the muscle cell. Structural adaptations consist of the synthesis of additional myofibrillar material or increased volume density of both interfibrillar and subsarcolemmal mitochondria. Transformation of fibre types at the level of the molecular structure of myosin seems possible with high-intensity training of long duration. Functional adaptations consist of higher activities of important enzymes in either anaerobic or aerobic energy metabolism and of larger intracellular stores of the respective substrates. All adaptations are highly specific and reversible through detraining or immobilization of the muscle. PMID- 4031777 TI - Malleability of the motor system: a comparative approach. AB - The various ways in which the power output of muscles can be changed are described. As a result of exercise and growth, force production is increased by an increase in the cross-sectional area of the fibres. This is associated with changes in the rate of synthesis and degradation of muscle proteins which lead to build up of the myofibrils. These then split longitudinally when they reach a critical size. This process is repeated so that the number of myofibrils increases very considerably. Also, during growth, the displacement is increased by increasing the length of the muscles. To do this more sarcomeres are produced in series along the length of the fibres. This is induced by stretch which also encourages fibre growth in girth as well as in length. Yet another way of changing the power output of a muscle is to change the types of muscle fibres (motor units) within the muscle. Fibre type transformation has been fibres (motor units) within the muscle. Fibre type transformation has been shown to occur with cross innervation and stimulation but it does not usually occur with exercise training. It has been possible, however, to change the fibre type proportions in young animals. Also, by combining stretch with stimulation, it has been possible for instance to make the fast glycolytic fibres add on fast oxidative type sarcomeres or even slow oxidation type sarcomeres. Interestingly, fibre transformation also occurs in some species of fish during acclimation to low temperatures in that the specific myofibrillar ATPase activity is increased. This means that the reduction in power output due to decreased temperature is to some extent compensated for by an increase in the intrinsic rate of shortening. EMG studies of fish swimming at different temperatures have shown that the acclimated fish can swim faster and can derive more aerobic sustainable power as a result of this change. PMID- 4031778 TI - How flexible is the neural control of muscle properties? AB - The issue addressed in this paper is to what extent are selected physiological properties and associated protein systems of muscle fibres controlled or regulated by neuronal systems. One extreme position would be that all muscle proteins are controlled completely by the neural system that innervates the muscle. The opposite position would be that none of the muscle proteins are under neural influence. Although the concept that there is complete neural control of all proteins has generally received more support, it is more likely that there is only partial neural control of some proteins. Identical physiological, morphological and metabolic properties of all muscle fibres within a motor unit would suggest a complete neural control of all protein systems in muscle fibres. However, evidence against this idea is provided by the marked heterogeneity in the activities of two enzymes, alpha glycerophosphate dehydrogenase and succinic dehydrogenase (SDH), and in the wide variations in muscle fibre cross-sectional areas among fibres of the same motor unit in the cat soleus and tibialis anterior. PMID- 4031779 TI - Design and performance of muscular systems: an overview. PMID- 4031780 TI - Adaptability of ultrastructure in the mammalian muscle. AB - All the skeletal muscle fibres taken from an adult mammal do not look alike. The structural differences are a result of adaptations which allow gradations in mechanical output to be achieved. The anatomy is described and the amounts of the subcellular components are measured by stereological techniques from electron micrographs. A population of normal, adult fibres is classified by the Z-line width, by the amounts of the mitochondria, T-system and terminal cisternae (TC), and by the isoforms of contractile proteins present. Classification of fibres by some of these ultrastructural components gives clusters named fast-twitch and slow-twitch types, but classification by other components gives a continuum of overlapping properties. Transformation from the fast- to the slow-twitch type or vice versa follows a specific alteration in the use of the fibre. The mechanical demand on the fibre is modified by changing the frequency of stimulation in the nerve with an implanted electrode. The time course of the changes in subcellular composition in the fibre during adaptation is followed for many weeks. Changes in the membrane systems begin within hours and are complete in days. Changes in the contractile proteins and metabolic systems begin in days and are complete in weeks. During these transitional phases of adaptation the fibres have an unusual complement of components never seen in a normal adult fibre. Extreme alterations, such as myofibril disassembly or supranormal amounts of mitochondria also result during some adaptive transitions. The aberrant appearance in the transitional fibres may be a result of doing the required mechanical work with a less than optimal set of proteins. At the end of the fibre type transformation, the fibre ultrastructure is indistinguishable from normal. PMID- 4031781 TI - From sarcomeres to whole muscles. AB - The series connection of sarcomeres in a muscle raises the possibility of instabilities due to some sarcomeres being capable of greater isometric tension than others, due to non-uniform activation, cross-sectional area or sarcomere length. Such instabilities are heavily damped by the force-velocity curve and stabilized by passive tension. The variation of active tension with sarcomere length may act to stabilize or destabilize the situation. Such instabilities can affect tension in a complex manner, causing both increases and decreases in different situations. Some examples of situations where sarcomere nonuniformities have been observed or inferred are given, and their mode of action explained. PMID- 4031782 TI - Storage and release of mechanical energy by active muscle: a non-elastic mechanism? AB - In frog muscle fibres, tetanically stimulated at a sarcomere length of about 2 micron, stretched at a velocity of 1 lengths-1 and released against a force equal to the maximum isometric, P0, a phase of rapid isotonic shortening takes place after release. As the amplitude of the stretch is increased from 1.5 to 9% of the initial length: (1) the amount of rapid isotonic shortening increases up to 9-10 nm per half sarcomere and (2) the stiffness of the fibre (an indication of the number of bridges attached) decreases to a value about equal to that measured during an isometric contraction. If a 5-10 ms delay is left between the end of stretch and release, the amount of rapid isotonic shortening increases to about 12 nm hs-1. A 300-500 ms delay, however, results in a decrease in rapid isotonic shortening to about 5 nm hs-1 and also results in a velocity transients against P0 that are similar to those described during release from a state of isometric contraction. It is concluded that the force attained after large, fast stretches is due to a greater force developed by each bridge and not to a greater number of bridges. After the elastic recoil (when the force is suddenly reduced to P0), these strained bridges are able to shorten by about 12 nm hs-1, suggesting that, during and immediately after stretching, they are charged to levels of potential energy greater than those attained in an isometric contraction. PMID- 4031783 TI - Excitation-contraction coupling: the link between the surface and the interior of a muscle cell. AB - The control of the contractile state of a muscle cell, a process called excitation-contraction coupling, involves a sequence of steps and is passed along through a series of cellular structures. The excitation of the fibre, initiated at the motor end-plate, spreads rapidly over the surface of the fibre and into the fibre along the T-system networks as an action potential. This excitation is coupled to the sarcoplasmic reticulum (SR) by a mechanism not yet identified with certainty. The SR then responds by releasing stored calcium from its interior compartment into the myoplasm. The diffusion and binding of this calcium to regulatory proteins initiates the mechanical events of contraction, which subsequently are turned off when calcium is removed from these regulatory binding sites. Some of this calcium may temporarily bind to proteins in the myoplasm, but eventually it gets pumped back into the internal compartment of the SR by a calcium-ATPase in the SR membrane. The system then is poised for a repeat performance. PMID- 4031784 TI - The influence of inactivity on membrane resting conductances of rat skeletal muscle fibres undergoing reinnervation. AB - The role of activity in the maintenance of the normal component resting conductances of skeletal muscle fibres has been evaluated in vitro in rat extensor digitorum longus muscle during reinnervation from 2 to 40 days (a) after crushing of the peroneus nerve and (b) after local application of tetrodotoxin (TTX) to the crushed nerve. Whereas membrane conductances were regained after crushing alone, they were not completely restored when impulse propagation was blocked with TTX. It is concluded that nerve trophic factors are of primary importance in the control of muscular membrane conductances, and that transmission at the endplate and the muscle usage triggered by it have a minor but significant effect. PMID- 4031785 TI - A cross-sequential analysis of developmental differences in speed of visual information processing. AB - Development of processing speed was examined in three backward masking studies. The first verified the central nature of backward masking for children aged 8 and 11 years and for adults. The second suggested that task requirements were equivalent for children similar to those in Study 1, and that age differences in performance were not attributable to nonprocessing variables. The main cross sequential study estimated speed of processing in 80 children (approximately 6 years to 13 years) and young adults using an inspection time task. Target exposure duration was varied to establish the time required to achieve a high level of discriminative accuracy. Estimates of processing speed increased until about 11-13 years of age; beyond this, the trend was less obvious, and it is possible that inspection time asymptotes at around the onset of adolescence. Performance improvement after 1 year could not be explained as resulting from practice since improvement among controls over a period of 2 weeks was significantly less. Correlations between estimates of inspection time made up to 2 years apart found the measure to be reliable. PMID- 4031786 TI - Attention to eye contact opportunity and facial motion by three-month-old infants. AB - Thirty-two 3-month-old infants participated in two experiments showing color videotapes of facial stimuli in a paired comparison format. In Experiment 1, the experimenter, serving as the stimulus, looked either directly at the infant or averted his gaze to the side; the face was presented either still or in motion. Eye contact opportunity had no effect while motion of the head was an effective attractor of visual fixation. In Experiment 2, the amount of available eye contact opportunity was parametrically varied by occluding the eyes with different patterns of blinking, each at the same rate. The no-motion 100% eye contact available condition received less attention than the three blinking stimuli, which were all equally attended to, though they varied with respect to the amount of eye contact opportunity they afforded. The contrast in effect of eye contact availability and rather subtle stimulus motion would imply that 3 month-old infants are comparatively insensitive to being the object of another's visual regard. PMID- 4031787 TI - More and more and more about more. AB - Three experiments explored the development of three linguistic aspects of more in children's speech. Subjects were 56 children between the ages of 2;6 and 6;0. Experiment 1 addressed the nature of the early semantic content of more. Experiment 2 examined the child's differentiation of mass more from count more. Experiment 3 explored the child's use of more as a comparative marker on adjectives. The results suggest, first, that the child initially stores the meaning of more with a prototype, rather than with some more systematic, featural representation. In addition, children's linguistic understanding of the dual use of more as a quantifier of mass amounts and count amounts does not appear to develop until long after they have been using more appropriately in unambiguous contexts. Finally, children learn to use more as a marker on comparatives only after they have acquired -er as a comparative marker, and some time after they have been using more successfully in nonadjectival constructions. PMID- 4031788 TI - A common major surface antigen on amastigotes and promastigotes of Leishmania species. AB - Enzymatic surface iodination and biosynthetic labeling with [35S]methionine, combined with immunoprecipitation by sera from patients with different forms of Leishmaniasis revealed a 65,000 Mr glycoprotein as the immunodominant moiety in promastigotes and amastigotes of the nine Leishmania species and isolates examined. Sera from patients with one form of Leishmaniasis recognized this component strongly, not only in the homologous, but also in the heterologous species. In addition to the crossreactivity displayed by immune sera, the 65,000 Mr glycoprotein (gp) common to all Leishmania species presented a characteristic shift to Mr 50,000 when samples were run in sodium dodecyl sulfate-polyacrylamide gel electrophoresis under nonreducing conditions. These results are in agreement with our previous studies (7), where a simple and similar profile was obtained for several geographic isolates of L. donovani, with a major surface glycoprotein of 65,000 Mr displaying the same characteristics described here. The structural similarity of the major 65,000 Mr gp of the six Leishmania species was demonstrated by Cleveland mapping. It is suggested that immunological specificities may be contributed by minor differences in glycosylation of this molecule. In keeping with recent data (13-15), where strong cross protection among different Leishmania species has been obtained by prophylactic immunization with irradiated whole promastigotes, this glycoprotein may be a good candidate for an antigen to be used for immunoprophylaxis of all forms of Leishmaniasis. PMID- 4031790 TI - Infantile colic. PMID- 4031791 TI - Routine screening for gestational diabetes reconsidered. PMID- 4031789 TI - Isolation and characterization of resident stromal macrophages and hematopoietic cell clusters from mouse bone marrow. AB - In situ studies with the mouse macrophage (M phi)-specific antibody, F4/80, have shown that resident M phi in femoral bone marrow (RBMM) form hematopoietic islands with immature myelomonocytic and erythroid cells (Hume, D. A., et al. 1983. J. Exp. Med. 158: 1522). We have isolated these islands (clusters) by collagenase digestion, purified them from single cells by velocity sedimentation, and analyzed their cellular content. The clusters, ranging from 5- to 100 cells, constituted approximately 7% of the total nucleated cells, and greater than 70% contained at least one strongly staining, F4/80+ central M phi. In comparison, less than 26% showed reactivity for alkaline phosphatase, a marker of fibroblastoid reticulum cells. Compared with the nonclustering population, clusters were enriched with RBMM, fibroblastoid cells, and immature hematopoietic cells, but depleted of mature granulocytes and erythrocytes. The RBMM population was purified from other cells in clusters by selective adherence to glass and was compared with resident peritoneal M phi (RPM) for morphology and the presence of antigens, receptors, and enzymes. RBMM spread more extensively than RPM and frequently extended delicate plasma membrane processes. These and subsequent differences were not attributable to the collagenase treatment. Both M phi populations stained positively with antibodies F4/80 and 2.4G2 (Fc receptor IgG1/2b), bore mannosyl/fucosyl receptors, and showed reactivity for acid phosphatase and nonspecific esterase I. In contrast to RPM, RBMM had no detectable Mac-1 antigen (CR3) or complement receptors, but bore higher levels of Fc receptors (IgG2a and IgG2b) and Ia antigens. In addition, RBMM possessed a novel hemagglutinin activity for unopsonized sheep erythrocytes, which was not present on RPM. RBMM showed no respiratory burst activity in response to zymosan particles, but ingested them avidly. The growth properties of clustering and nonclustered populations were compared by measurement of [3H]thymidine incorporation and progenitor assays. Cells in clusters incorporated three- to fourfold more thymidine than nonclustered cells even in the absence of exogenous growth factors, and autoradiography demonstrated that RBMM made contact with proliferating cells. In contrast, the clusters contained over threefold fewer granulocyte/M phi progenitors compared with nonclustering cells. When clusters were cultivated for up to 3 d, there was rapid outgrowth of monocytes and fibroblastoid cells. These studies demonstrate that RBMM bear a distinct morphology and phenotype.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 4031792 TI - Blood glucose monitoring in a type II diabetic. PMID- 4031793 TI - Nutritional rickets in breast-fed infants. AB - A ten-year literature review was prompted by the fortuitous discovery of nutritional rickets in a "well child." Sixty-three cases were identified, suggesting that this disease is not so rare as thought. Rickets should be considered in the differential diagnosis of nonspecific musculoskeletal complaints and poor growth. Vitamin D supplementation in breast-fed children should be prescribed more often. PMID- 4031794 TI - Why women choose trial of labor or repeat cesarean section. AB - Despite growing interest in vaginal birth after previous delivery by cesarean section, virtually no studies have examined patient decision making in any depth. This paper examines the social content and cognitive structure of pregnant women's decisions to attempt delivery by trial of labor or for elective repeat cesarean section. Three features of childbirth care strategies are discussed. First, social goals are as central to women's decisions as are medical risks. Second, women reinforce their decisions by defining multiple benefits for the preferred alternative and multiple hazards for the rejected alternative. Third, women do not attempt to assess the probabilities of particular outcomes, but instead construct mental images of anticipated events based upon past childbirth experience and expected consequences of the preferred course of action. PMID- 4031795 TI - Ethics of clinical trials in family medicine. AB - In this paper several issues are examined that arise from conducting randomized clinical trials in a family practice setting. The distinctive research tradition in family practice involves a patient's primary care physician performing an experimental investigation that usually, though not invariably, is focused on common health problems. Representative clinical trials are presented as examples that illustrate two ethical difficulties evoked by such research: a potential violation of the primary care physician's therapeutic imperative to provide the best possible treatment for his or her patient, and the likelihood that the type of physician-patient relationship fostered in family practice significantly diminishes the capacity of the patient to give true informed consent. In an attempt to resolve these ethical difficulties, a model of moral reasoning is presented that is based on easily understood ethical principles and is applicable to actual clinical decision making. Using that model, a tentative set of rules or guidelines is offered for implementing clinical trials in family medicine. PMID- 4031796 TI - Geriatric teaching in family practice residencies. PMID- 4031797 TI - A contractual model for accountability and financial stability in a community based family practice residency. AB - A contractual model is described that defines the relationship between the hospital and the Department of Family Practice. The model provides institutions supporting graduate training in family practice with a method that is accountable and cost effective. Application of this model at a community hospital over a five year period is presented. The model resulted in expansion of the family practice residency, increased faculty numbers, increased income for the faculty, and control of the institution's cost of graduate medical education. PMID- 4031798 TI - The role of the family physician in critical care. PMID- 4031799 TI - Discussion of "Photographic techniques of concern in metric bite mark analysis". PMID- 4031800 TI - Discussion of "Fiber evidence: laboratory methods and observations from casework". PMID- 4031801 TI - Evaluation of antisera for bloodstain grouping. II. Ss, Kell, Duffy, Kidd, and Gm/Km. AB - Thirty-one different examples of commercially available blood grouping antisera specific for the S, s, K, k, Fya, Fyb, Jka, and Jkb antigens and anti-human globulin sera were serologically evaluated with red cells and in absorption elution tests to determine their applicability to bloodstain antigen determinations. Nineteen examples of commercially available antisera specific for various Gm and Km antigens and their corresponding anti-D reagents were likewise evaluated in inhibition tests with sera and bloodstains. Elution tests with the blood grouping antisera and inhibition tests with the Gm/Km antisera on a series of aging bloodstains on cotton cloth, and on bloodstains on a number of different substrata, demonstrated that properly evaluated commercial antisera are useful reagents for bloodstain grouping in forensic serology. PMID- 4031802 TI - Determination of cross-reactant drugs with a new morphine radioimmunoassay procedure. AB - A study to determine the specificity of a new morphine radioimmunoassay (RIA) procedure was performed on 23 drugs of forensic science interest. Spiked whole blood and urine specimens were analyzed and the apparent morphine concentrations determined. All compounds analyzed showed low cross-reactivity, indicating a high specificity for morphine. PMID- 4031803 TI - Illicitly imported heroin products: some physical and chemical features indicative of their origin. Part II. AB - Samples taken from seizures of imported illicit heroin preparations of known geographical origin have been examined. The typology developed in a previous survey of illicit heroin products is applicable to virtually all the samples studied in this work. On the basis of these observations it is possible to give an opinion as to the origin of some samples of illicit heroin of unknown provenance. The observation in the previous survey that unrelated samples of illicit heroin possess unique chemical profiles has been confirmed by the present results. PMID- 4031804 TI - Toxicological analysis of amobarbital and glutethimide from bone tissue. AB - Author examined cadaver organs and bone samples (sternum, rib) of drug poisoning cases. Following suitable procedures, active drug components (amobarbital, glutethimide, and so forth) were identified by gas chromatography/mass spectrometry (GC/MS). Based on results of quantitative GC analysis, relationships were sought between the active agent concentrations measured in the organs and the bone samples. PMID- 4031805 TI - Psychiatric evaluations of sexual offenders. AB - Ninety-five defendants charged with sexual offenses were evaluated in a forensic psychiatry clinic. Their psychiatric diagnoses, as well as social, demographic, and criminal characteristics, were studied. Almost half were found to have personality disorders, while one-fifth were given a diagnosis of schizophrenia, affective disorder, or an atypical psychosis. Surprisingly few were diagnosed as having a paraphilia. PMID- 4031806 TI - Forensic psychiatric evaluations of women accused of felonies: a three-year descriptive study. AB - Descriptive statistics are presented for 95 female offenders evaluated in the Forensic Psychiatry Clinic for the New York Criminal and Supreme Court (First Judicial District). Demographic data, criminal charges, psychiatric diagnoses, prior mental health treatment, and victims of offenses are examined. PMID- 4031807 TI - Geriatric felons examined at a forensic psychiatry clinic. AB - Descriptive statistics are presented on 25 defendants in the geriatric age range (aged 62 to 78 years old). Demographic variables, criminal charges, medical, neurological and psychiatric illnesses, prior criminal offenses, and final dispositions of the cases are tabulated, and implications for the criminal justice system and social services are discussed. PMID- 4031808 TI - Collection of trace evidence from bombing victims at autopsy. AB - The body recovered from the scene of a bombing may contain important trace evidence that links the suspect to the crime. Recognizing the lack of guidelines for evidence removal from the body, we have prepared a protocol to guide the pathologist in the collection of trace evidence from the bombing victim. Case material used in the development of the protocol included 13 bombing fatalities reported to the St. Louis Medical Examiner's Office since 1975. PMID- 4031809 TI - A procedure for the investigation of anesthetic/surgical deaths. AB - A procedure for the investigation of surgical/anesthetic deaths is presented which allows for clearly defined jurisdictional assessment and correlates the autopsy and toxicological findings with the pathophysiology of the anesthetic/surgical event. This procedure facilitates an accurate certification of the cause of death in patients who die during surgery and anesthesia. PMID- 4031810 TI - Variations in vitreous humor chemical values as a result of instrumentation. AB - Urea nitrogen, glucose, sodium, potassium, and chloride were measured in common vitreous humor samples using a variety of instruments. There was found to be variation in values obtained by the different procedures for each of these constituents. The variation in electrolyte values between the different procedures can pose real problems in attempting to determine the presence of an antemortem dehydration or low salt condition. Possible reasons for these variations are discussed, and the normal range of values of both sodium and chloride for the different instrumentalities is provided. However, variations in values for both urea nitrogen and glucose would not pose any problems of interpretation for forensic science evaluations. PMID- 4031811 TI - Decomposition of buried bodies and methods that may aid in their location. AB - This is the second report on an ongoing study conducted to collect data on the decompositional rates of human cadavers and the first on buried cadavers. Six unembalmed human cadavers were buried separately in unlined trenches of various depths and allowed to naturally decompose for a time period ranging from a month to a year. During the period of burial, data were collected daily on the air, soil, and cadaver temperature at each burial site. At the end of each specified burial period the cadavers were exhumed and examined for the degree of decomposition which had taken place as well as changes in the soil pH, surface vegetation, and carrion insect activity. Analysis of the data shows that the decomposition rate of buried cadavers is highly dependent on the depth of burial and environmental temperatures. The depth at which the cadaver was buried also directly affected the degree of soil and vegetational changes as well as access by carrion insects. Application of this information can contribute to a more accurate estimation of time since death of a buried corpse and may aid in the location of such corpses. PMID- 4031812 TI - Age estimation from the rib by phase analysis: white females. AB - Metamorphosis at the sternal extremity of the rib has already been established as a reliable indicator of age at death. Using a sample of white males, it was shown that an accurate estimation of age can be made by direct examination of the bone itself. However, because of sexual differences in hormonal production and dimorphism in the skeleton, the present study was carried out to develop an appropriate standard for age determination from the sternal rib in white females. The sample consisted of 86 ribs of known age, sex, and race. Observations were made at the costochondral junction with special attention to pit formation (its shape and depth), changes in the walls and rim surrounding it, and overall bone density and texture. Based on changes in these areas, the ribs were separated into nine phases (0 through 8). The most rapid metamorphosis occurred in Phases 1 through 4 (mean ages 14-28) with changes noticeable at 3 to 4 year intervals. After mean age 28, this process slowed, considerably expanding the interval between phases to 10 to 15 years. The female ribs showed both earlier initial pit formation and a different morphologic pattern of aging as compared with males. Statistical analysis revealed that the features chosen to delineate the phases are valid predictors of age. This study has shown that the sternal rib can provide an accurate estimation of age in females spanning a mean age of 14 to 76 years. PMID- 4031813 TI - Cocaine-induced psychosis and sudden death in recreational cocaine users. AB - Fatal cocaine intoxication presenting as an excited delirium is described in seven recreational cocaine users. Symptoms began with the acute onset of an intense paranoia, followed by bizarre and violent behavior necessitating forcible restraint. The symptoms were frequently accompanied by unexpected strength and hyperthermia. Fatal respiratory collapse occurred suddenly and without warning, generally within a few minutes to an hour after the victim was restrained. Five of the seven died while in police custody. Blood concentration of cocaine averaged 0.6 mg/L, about ten times lower than that seen in fatal cocaine overdoses. Police, rescue personnel, and emergency room physicians should be aware that excited delirium may be the result of a potentially fatal cocaine intoxication; its appearance should prompt immediate transport of the victim to a medical facility. Continuous monitoring, administration of appropriate cocaine antagonists, and respiratory support will hopefully avert a fatal outcome. PMID- 4031814 TI - Discontinuous polyacrylamide gel electrophoresis for typing haptoglobin in bloodstains. AB - A routine method is described for obtaining reproducible haptoglobin patterns from bloodstains by discontinuous polyacrylamide gel electrophoresis. By employing a stacking gel, proteins from bloodstain extracts are concentrated into narrow zones, before entering the resolving gel. This effect yields highly resolved haptoglobin patterns. Therefore, laboratories without the specialized equipment and expertise for polyacrylamide gradient gel preparation can still obtain highly resolved haptoglobin patterns from bloodstains. PMID- 4031815 TI - Determination of ABH secretor status by an electronic quantitation method. AB - Blood Group A and B substances in secretor (Se) and nonsecretor (se) salivas were tested by means of an electronic data processing-hemagglutinin-inhibition test (EDP-HAIT) with immunoglobulin M (IgM) isohemagglutinins. Besides a difference in quantity, the blood group substances in Se saliva showed high binding efficiencies compared with those in se saliva. EDP-HAIT with IgG isohemagglutinins proved no difference in the binding efficiencies of Se and se salivas. The determination of secretor status by EDP-HAIT with IgM isohemagglutinin was accurate because the conclusion was obtained based on two different quantitative results. Secretor status of some salivas in gargled water could be determined by comparing the binding efficiencies. PMID- 4031816 TI - 1H nuclear magnetic resonance of heroin's D ring. AB - The 1H nuclear magnetic resonance (NMR) chemical shifts and coupling constants of heroin's D ring H-15 alpha, H-15 beta, and H-16 alpha, and H-16 beta are presented. These assignments were accessible through the introduction of a double bond (delta 15,16) in heroin. The resulting compound, delta 15,16 didehydroheroin, was subjected to deuterium exchange or stereoselective reduction or both. Reduced products d1-16 alpha heroin d2-15 alpha, 15 beta-heroin, and d3 15 alpha, 15 beta, 16 alpha-heroin are presented. Heroin with deuterated acetyls is also presented for 1H NMR spectral clarity in the D ring area. PMID- 4031817 TI - Analytical characterization of isoheroin. AB - The synthesis of isoheroin is presented with the analytical data (mass spectroscopy [MS], nuclear magnetic resonance [NMR], infrared spectroscopy [IR], and gas liquid chromatography [GLC]) for this compound. Comparison between analytical results for heroin and isoheroin shows differentiation is possible. PMID- 4031818 TI - Isotachophoretic analysis of bloodstains: differentiation of human, menstrual, bovine, and ovine bloods. AB - Isotachophoresis, a technique to separate components by constant current electrophoresis, was used to differentiate between bloodstains of male, female, menstrual, bovine, and ovine bloods on cotton cloth and filter paper. Bloodstain analysis by isotachophoresis of stains from male and female subjects showed identical cationic patterns, but gave different profiles in the anionic system. Plasma had one extra peak in the anionic system when compared to the profile of serum. This extra peak is due to the presence of fibrinogen in plasma. Some hemoglobin peaks overlapped with serum protein peaks, but these could be identified by comparisons at lower concentrations. Menstrual blood had a much different pattern than normal human blood as was expected since many more compounds are found in menstrual blood than in normally circulating blood. Human, bovine, and ovine bloodstains showed different profiles both in the cationic and anionic systems. These results indicate that isotachophoresis can be used for the rapid and simple analysis of bloodstains to differentiate reliably human male, female, and menstrual blood and also to distinguish human bloodstains from those of cattle or sheep. PMID- 4031819 TI - Fatal in utero salicylism. AB - An aspirin overdose by an eight-month primigravida proved to be the mechanism of death for the fetus. Clinical progress of the mother and postmortem concentrations of salicylate in the fetus are listed exhibiting the fetal survival time of about 18 to 20 h post ingestion by the mother. PMID- 4031820 TI - The asymmetrical remodelling of two neurosurgical burr holes: a case study. AB - A human skull identified as that of a 16-year-old female who had been reported missing about 3 years before the discovery of the specimen displayed evidence for the asymmetrical remodelling of bilateral neurosurgical burr holes. While one of the holes retained its original size and shape, gross evidence for the contralateral lesion had virtually disappeared. Initially, the open lesion was mistakenly suspected to be a recent bullet hole. PMID- 4031821 TI - Two bite mark cases with inadequate scale references. AB - Most literature addressing comparisons between epidermal bite marks and the perpetrator's bite pattern mandates fastidious coordination between the size of the compared reproductions. While ideal, this is not possible in every case and inability to control this variable in selected cases may not necessarily invalidate the comparison. The first case involves a known perpetrator. All photographic measurements were recorded with acceptable techniques to discover a serious discrepancy in arch size. The second case was degraded by the absence of a ruler in a tangentially made photograph of a bite mark. In both cases, the weight of the conclusions were lessened by these problems but the impartial handling of the evidence and explanation of discrepancies offered credibility to the analyses. Both cases illustrate that a technical infraction in processing and recording bite marks, though serious, need not automatically preempt the analysis. PMID- 4031822 TI - Childhood suicide: a report of four cases. AB - A study of childhood suicide in individuals aged twelve years or less was performed on the case files of the Office of the Medical Examiner of Metropolitan Dade County in Miami, FL, over the eight-year period from 1977 to the present. Four cases were collected; these are presented in some detail. A discussion then ensues along with a review of pertinent literature concerning this phenomenon. PMID- 4031823 TI - Reappraisal of diffusion, solubility, and consumption of oxygen in frog skeletal muscle, with applications to muscle energy balance. AB - Previously we tested the validity of the one-dimensional diffusion equation for O2 in the excised frog sartorius muscle and used it to measure the diffusion coefficient (D) for O2 in this muscle and the time course of its rate of O2 consumption (Qo2) after a tetanus (Mahler, 1978, 1979, J. Gen. Physiol., 71:533 557, 559-580, 73:159-174). A transverse section of the frog sartorius is in fact well fit by a hemi-ellipse with width divided by maximum thickness averaging 5.1 +/- 0.2. Using the previous techniques with the two-dimensional diffusion equation and this hemi-elliptical boundary yields a value for D that is 30% smaller than reported previously; the revised values at 0, 10, and 22.8 degrees C are 6.2, 7.9, and 10.8 X 10(-6) cm2/s, respectively. After a tetanus at 20 degrees C, Qo2 rose quickly to a peak and then declined exponentially, with a time constant (tau) approximately 15% faster than that reported previously; tau averaged 2.1 min in Rana temporaria and 2.6 min in Rana pipiens. A technique was devised to measure the solubility (alpha) of O2 in intact, respiring muscles, and yielded alpha (muscle)/alpha (H2O) = 1.26 +/- 0.04. With these modifications, the values for O2 consumption obtained with the diffusion method were in agreement with those measured by the direct method of Kushmerick and Paul (1976, J. Physiol. [Lond.]., 254:693-709). Using results from both methods, at 20 degrees C the ratio of phosphorylcreatine split during a tetanus to O2 consumption during recovery ranged from 5.2 to 6.2 mumol/mumol, and postcontractile ATP hydrolysis was estimated to be 13.6 +/- 4.1 (n = 3) nmol/mumol total creatine. PMID- 4031825 TI - Flavivirus infection enhancement in macrophages: an electron microscopic study of viral cellular entry. AB - The mode of entry of West Nile virus (WNV) into the macrophage-like cell line P388D1 was investigated at the electron microscopical level using synchronized infections. The presence of the antiviral monoclonal antibody F6/16A at a concentration that enhanced viral attachment to P388D1 cells ninefold made no difference to the entry pathway of WNV. In both the absence and presence of F6/16A the initial uptake of single viral particles was mediated by coated pits, and started within 30 s of warming the cells to 37 degrees C. Viral particles later appeared in fully or partially coated vesicles and later in uncoated prelysosomal endocytic vacuoles before degradation in lysosomes. However, aggregates of viral particles (five or more virus particles in cross-section), appeared to be phagocytosed whole by cells in a process which involved aggregates being engulfed by extensions of the plasma membrane. This process exhibited a slower time course than the uptake of single viral particles, becoming prominent 15 to 30 min after warming the cells to 37 degrees C. The involvement of a prelysosomal vacuolar compartment in the entry process was shown by a failure to stain for acid phosphatase. This compartment could be specifically loaded with viral particles when viral internalization occurred at 20 degrees C in the presence of 50 mM-ammonium chloride. PMID- 4031824 TI - First-order kinetics of muscle oxygen consumption, and an equivalent proportionality between QO2 and phosphorylcreatine level. Implications for the control of respiration. AB - In frog sartorius muscle, after a tetanus at 20 degrees C, during which an impulse-like increase occurs in the rate of ATP hydrolysis, the rate of O2 consumption (QO2) reaches a peak relatively quickly and then declines monoexponentially, with a time constant not dependent on the tetanus duration (tau = 2.6 min in Rana pipiens and 2.1 min in Rana temporaria). To a good approximation, these kinetics are those of a first-order impulse response, and the scheme of reactions that couple O2 consumption to extramitochondrial ATP hydrolysis thus behaves as a first-order system. It is first deduced and then demonstrated directly that while QO2(t) is monoexponential, it changes in parallel with the levels of creatine and phosphorylcreatine, with proportionality constants +/- 1/tau p, where p is the P/O2 ratio in vivo. From this, it is further deduced that the mitochondrial creatine kinase (CK) reaction is pseudo first order in vivo. The relationship between [creatine] and QO2 predicted by published models of the control of respiration is markedly different from that actually observed. As shown here, the first-order kinetics of QO2 are consistent with the hypothesis that respiration is rate-limited by the mitochondrial CK reaction; this has as a corollary the "creatine shuttle" hypothesis. PMID- 4031826 TI - Kinetics of synthesis of respiratory syncytial virus glycoproteins. AB - The synthesis of the two respiratory syncytial (RS) virus glycoproteins (VP66 and VP84) was examined under standard conditions and after treatment with tunicamycin and monensin. The protein backbone for VP66, the fusion protein (F1,2) is cotranslationally glycosylated to form F0, which is cleaved to form F1,2 by 20 min of chase. Monensin treatment inhibited the cleavage of F0 over an 80 min chase period, indicating that this occurred late in the transit of F0 through the Golgi apparatus or after exit from the Golgi apparatus. Tunicamycin treatment resulted in the synthesis of a 50K to 55K unglycosylated F0 which is cleaved to a 40K protein. VP84, the large glycoprotein, contains a protein backbone of only 26K to 30K which is modified by N-linked and probable O-linked glycosylation. Tunicamycin treatment results in the synthesis of a 70K protein (p70) which incorporates [3H]glucosamine and [3H]fucose but not [3H]mannose. Glycosylated precursors varying in mol. wt. from 29K to 45K (p45) are found in infected cells at regular 2K to 3K intervals, producing a 'ladder' effect. The step from p45 to VP84 is severely delayed by monensin treatment thereby enhancing the 'ladder' effect of the precursors. PMID- 4031827 TI - Characterization of the endogenous retroviral envelope glycoproteins found in the sera of ev3 and ev6 chickens. AB - Chicken sera may contain components that immunologically crossreact with avian retroviral glycoprotein. Sera from chickens carrying the endogenous viral loci ev3 and ev6 contain glycoproteins with molecular weights of approx. 85 000, which on the basis of tryptic peptide analysis are related to exogenous viral glycoprotein. Such endogenous viral glycoproteins are present in a free form, lacking disulphide-bonded gp35. PMID- 4031828 TI - Inadequacy of immunoglobulin M hepatitis B core antibody in detecting acute hepatitis B virus infection in infants of HBsAg carrier mothers. AB - To study the usefulness of IgM hepatitis B core antibody (anti-HBc IgM) for detecting hepatitis B virus infections in infants of hepatitis B surface antigen (HBsAg) carrier mothers, serial serum samples from 86 infants of carrier mothers were tested for anti-HBc IgM with a highly specific enzyme immunoassay. Asymptomatic hepatitis B infection occurred frequently in infants under 12 mo of age. Anti-HBc IgM never became positive in 25 infants infected under 9 mo old. It was positive in only 1 of 6 infected at 9 mo and 4 of 13 infected at 12 mo of age. The IgM antibody lasted for less than 6 mo. Although the infection was delayed in 28 infants receiving hepatitis B immune globulin, the poor anti-HBc IgM response did not seem to be due to the immune prophylaxis. Our study clearly indicates the limitation of anti-HBc IgM for detecting acute hepatitis B infection in infants born to HBsAg carrier mothers. PMID- 4031829 TI - Detection of RS-virus IgG-subclass-specific antibodies: variation according to age in infants and small children and diagnostic value in RS-virus-infected small infants. AB - The variation according to age of RS-virus IgG-subclass specific antibodies was investigated by ELISA in 140 acute phase sera from 140 infants and children 1-47 mo of age who were hospitalized with acute respiratory disease. Sixty-nine of these serum samples were obtained from patients with RS-virus infections. Mean OD values of IgG-1 antibodies decreased corresponding to the decrease in maternal antibodies. In patients with RS-virus infections, the mean IgG-1 OD values increased in children who were 3 yr old, but in patients without RS-virus infections this increase was observed in children at 1 yr of age. RS-virus IgG-3 antibodies were detected only in children 1-3 yrs of age, and only in 18% of samples from children without RS-virus infections. The concept of the transient nature of RS-virus IgG-3 antibodies as compared with RS-virus IgG-1 antibodies is supported by these results. RS-virus subclass specific antibodies were studied in paired serum samples from 12 infants 1-5 mo of age with acute lower RS-virus disease. IgG-1 antibodies developed in six infants, but only in one of six infants aged 1-3 mo. IgG-3 antibodies developed in nine infants, including four of six infants who were 1-3 mo old. These results suggest that in small infants with RS-virus infections the detection of IgG-3 antibodies is of higher diagnostic value than the detection of IgG-1 antibodies. PMID- 4031830 TI - Rising ranks of homeless seen as health care problem. PMID- 4031831 TI - The specialty of physicians in relation to longevity and mortality. PMID- 4031832 TI - A method of plastic foreign body removal. PMID- 4031833 TI - Treatment of male infertility. PMID- 4031834 TI - Surgical management of occlusive disease of the aortic arch. PMID- 4031835 TI - Treatments for glaucoma today. PMID- 4031836 TI - Metastasis to leiomyoma. PMID- 4031837 TI - Coping and depression. The relative contribution of internal and external resources during a life cycle transition. AB - This study addresses two questions relevant to psychiatric epidemiological models of the stress-distress relationship: Are personality and social support resources independent phenomena or highly correlated? and What are the relative contributions of these two types of resources in protecting against the development of depressive symptomatology? A cohort of beginning medical students was administered self-report questionnaires measuring social supports, locus of control, interpersonal dependency, and depressive symptomatology. On the basis of correlation and regression analysis, the data show that the personality characteristics more strongly predict depressive symptomatology than do social supports, and that social supports are unrelated to locus of control but directly correlated with interpersonal dependency. The authors discuss these findings in the context of a life cycle transition. PMID- 4031838 TI - Psychiatric manifestations of right hemisphere infarctions. AB - Five right-handed patients (aged 45 to 78 years) developed acute psychotic disturbances in conjunction with infarcts in the right hemisphere. Their presentation was marked by agitation, inattention, suspiciousness, paranoid delusions, hallucinations, and lack of appropriate concern. Several of these patients initially received primary psychiatric diagnoses. Although neurological findings indicative of right hemisphere involvement could also be elicited, these were generally overshadowed by the more dramatic behavioral alterations. The electroencephalogram and computerized axial tomography were positive in most cases. These cases demonstrate that the possibility of a right hemisphere lesion needs to be entertained in patients who present with an atypical psychotic episode. PMID- 4031839 TI - Psychosocial childbearing stress and metabolic control in pregnant diabetics. AB - The authors tested the relationship between psychosocial childbearing stress factors and metabolic control in a research sample of 39 pregnant insulin dependent diabetic women. Subjects were selected using rigorous exclusion criteria from a population of more than 200 pregnant diabetic patients assessed in a University National Institutes of Health Center. Metabolic control was determined by plasma levels of preprandial day, night, and early morning fasting glucose, urinary ketones, and glycosylation of hemoglobin. Differences in plasma glucose concentrations and urinary ketone levels at several times during the day and night were associated with psychosocial stress factors. A similar relationship between stress and levels of diabetic control could not be demonstrated by hemoglobin A1 assay, a result contradicting most prior studies of adolescent populations. These findings are compatible with a biopsychosocial model of diabetes mellitus and emphasize the importance of using several different measures of diabetic control to determine stress-control relationships. PMID- 4031840 TI - MMPI critical item characteristics of the DSM-III borderline personality disorder. AB - This study attempted to distinguish the borderline personality disorder (BPD) from other personality disorders (OPD) on the basis of the Lachar and Wrobel critical item list. Seventy-five male psychiatric inpatients with diagnoses fitting DSM-III criteria for BPD and OPD and ranging in age from 24 to 47 years completed the MMPI. Lachar's critical item set, composed of 111 items taken from the MMPI, was then selected from each of the 75 subjects' response items. BPD and OPD patients significantly differed on only the Lachar Substance Abuse subscale. Implications of this study are discussed with regard to the concept that personality structure involves a continuum of psychopathology. The Lachar critical item list provided support for drug abuse as part of the diagnostic criteria for BPD and displayed promise for identifying areas of psychopathology on which treatment may be focused. PMID- 4031841 TI - Effect of L-tryptophan on electroconvulsive therapy seizure time. AB - L-Tryptophan, the amino acid precursor of serotonin and several other monoamines, has frequently been employed as an adjunct with tricyclic antidepressants and monoamine oxidase inhibitors to increase their effectiveness in treating affective disorders. Combined use of L-tryptophan with electroconvulsive therapy (ECT) has generally not been successful and, in fact, may actually have a deleterious effect upon treatment. A case of decreased seizure duration due to an L-tryptophan-ECT interaction is presented and its implications discussed. PMID- 4031842 TI - Modifications of sleep parameters in the rat by (+)- and (-)-3-PPP. AB - The effects of subcutaneous administration of the two enantiomers of 3-(3 hydroxyphenyl)-N-n-propylpiperidine (3-PPP), a new dopamine analogue, were studied with regard to their effects on sleep parameters in the rat. The studies with both enantiomers were carried out taking into account their different effects on central dopaminergic receptors. At low doses they act preferentially as autoreceptor agonists; at higher doses the (+)-form is also an agonist while the (-)-form acts as an antagonist at postsynaptic dopamine receptors. The results showed the following: (1) with the high dose of (+)-3-PPP there was no change in REM sleep, but a marked increase in wakefulness; (2) with the high dose of (-)-3-PPP there was a significant increase in REM sleep and in the mean duration of REM episodes; (3) with the low dose of (+)-3-PPP similar results to those described for high-dose (-)-3-PPP were obtained; (4) there was no significant alteration of sleep parameters with the low dose of (-)-3-PPP. The data are discussed in terms of an active role for dopamine in the regulation of REM sleep. PMID- 4031843 TI - The relationship of free and conjugated catecholamines in plasma and cerebrospinal fluid in cerebral and meningeal disease. AB - The concentration of free and conjugated norepinephrine (NE), epinephrine (E) and dopamine (DA) were measured by a modified radio-enzymatic assay in the plasma and in the cerebrospinal fluid (CSF) of 45 patients with normal and in 21 patients with disturbed blood-CSF barriers. In patients with an undisturbed blood-CSF barrier the free NE and E in CSF were 128 +/- 45 ng/l and 27 +/- 20 ng/l (mean values +/- S.E.), respectively, and represented about 50% of the average plasma values. Mean DA was not different in plasma (47 +/- 22 ng/l) and in CSF (41 +/- 19 ng/l). Both in plasma and in CSF, considerable higher free catecholamine (CA) levels were measured in patients with dysfunction of the blood-CSF barrier. In one patient with bacterial meningitis twofold higher concentrations of free NE and DA in CSF as compared with plasma were detectable. Sulfate conjugates of catecholamines are predominant in plasma and CSF. The contribution of conjugated CA to total CA in plasma from patients with normal blood-CSF barrier averaged 69.7%, 63.1% and 98.1% for NE, E and DA, respectively and was significantly lower in the CSF (p less than 0.001). In patients with disturbed blood-CSF barrier, the increases of conjugated CA were more pronounced in CSF than in plasma. Further, the contribution of conjugated NE and E to total NE and E in CSF was not only increased in patients with bacterial meningitis, but also in patients with renal insufficiency compared to the "control" patients (p less than 0.02 and p less than 0.001 resp.). Free and conjugated NE, E and DA in the plasma and CSF were related significantly (p less than 0.01 resp.) with stronger correlation for conjugated CA (p less than 0.001 resp.). These results together with findings in the literature, suggest that there is little or no rostral-caudal gradient in CSF CA conjugate concentrations and that even in patients with intact blood-CSF barrier plasma conjugated CA concentrations influence those in CSF. Thus only free CA levels in CSF may reflect the central adrenergic activity. PMID- 4031844 TI - Effects of rolipram, a novel antidepressant, on monoamine metabolism in rat brain. AB - The phosphodiesterase inhibitor and putative antidepressant rolipram (0.3-30 mg/kg i.p.) stimulated the accumulation of dopa following inhibition of the aromatic amino acid decarboxylase with 3-hydroxybenzylhydrazine HCl dose dependently in all brain regions investigated, suggesting that both dopamine and noradrenaline synthesis was enhanced. The stimulatory effect of rolipram on dopa accumulation in dopamine rich regions persisted even after pretreatment with gamma-butyrolactone which by itself increased dopa accumulation three fold. Following inhibition of catecholamine synthesis with alpha-amethyl-p-tyrosine rolipram accelerated the disappearance of noradrenaline and slowed the disappearance of dopamine. At low doses rolipram tended to reduce the pargyline induced accumulation of 3-methoxytyramine. Rolipram attenuated the accumulation of 5-hydroxytryptophan in the neocortex and the diencephalon of 3 hydroxybenzylhydrazine HCl pretreated rats. The data suggest that rolipram enhances noradrenergic transmission by direct stimulation of tyrosine hydroxylase and by an increase of neuronal activity. Despite a stimulatory effect on tyrosine hydroxylase rolipram does not appear to alter dopamine release and metabolism to a large extent. In view of the occurrence of head-twitches the rolipram-induced reduction of 5-hydroxytryptamine metabolism may be due to feedback inhibition. PMID- 4031845 TI - Monoamine distribution on the ventral surface of the rat medulla oblongata. AB - The distribution of monoamine transmitters in the area near the ventral surface of the rat medulla oblongata was studied using the Falck-Hillarp histofluorescence method. Histological examination and scanning electron microscopy of these regions were also performed. It was found that there is a wide area dense with catecholamine terminals in the external layer of the ventral medulla oblongata. 5-Hydroxytryptamine-containing terminals and nerve cell bodies on and near the surface were also found. Due to their superficial localization these monoamines may influence the content of cerebrospinal fluid and in this way have effects on cardiovascular and other physiological functions. PMID- 4031846 TI - Specific in vivo binding of 3H-spiperone to individual lobes of the pituitary gland of the rat. Evidence for the labelling of dopamine receptors. AB - The in vivo binding of 3H-spiperone to individual lobes of the pituitary gland was studied after intravenous injections in unanesthetized male rats. The binding was found to be saturable and reversible. The percentage of total binding of 3H spiperone that was specific binding was highest in the intermediate (approximately equal to 75%) and lowest in the posterior (approximately equal to 35%) lobes. The regional distribution of 3H-spiperone binding 1 hour after injections was the following: intermediate greater than anterior greater than posterior. Pharmacological analysis of the in vivo 3H-spiperone binding showed that dopamine agonists (e.g. bromocriptine, N-n-propylnorapomorphine) and antagonists could prevent the in vivo binding of 3H-spiperone in all three parts of the gland. The substituted benzamide drugs remoxipride and raclopride blocked the in vivo 3H-spiperone binding in the anterior and intermediate lobes but did not reduce the 3H-spiperone binding in the posterior part, except when given in very high doses. Taken together, the present study has shown that 3H-spiperone can be used in studies of the dopamine receptors in the anterior, intermediate and posterior lobes of the pituitary gland, but the proportion of non-specific binding is higher than in the striatum. The use of in vivo 3H-spiperone binding may thus be a useful method to study the regulation and pharmacology of these receptors in situ. PMID- 4031847 TI - The central morphology of the giant interneurons and their spatial relationship with the thoracic motorneurons in the cockroach, Periplaneta americana (Insecta). AB - Three groups of giant fibers are found in the cockroach ventral nerve cord. A latero-dorsal group (dorsal GIs), a latero-ventral group (ventral GIs) and a medio-ventral group. The morphology of all three groups of fibers within the thoracic ganglia is described. The morphology of the dorsal and ventral GI pathways in the abdominal and suboesophageal ganglia is also described. The projection patterns of the neurons in each ganglion are remarkably similar which suggests a common function. When motorneurons 5rl (depressor) and 6Br4 (levator) are stained simultaneously with the dorsal and ventral GI groups, some branches from both motor and giant neurons converge. The branching of the remaining medio ventral group of fibers and their proximity to areas receiving motorneuronal input suggests that these are the small diameter axons described by Dagan and Parnas (1970). PMID- 4031848 TI - The central morphology of mechanoreceptor afferents in the metathoracic leg of the cockroach, Periplaneta americana (Insecta). AB - The sensory arborizations of the femoral chordotonal organ (FECO), trochanteral campaniform sensilla (CS) and the trochanteral hairplate (THP) are restricted to the ipsilateral hemiganglion and possess large dendritic fields in the dorsal and ventral neuropiles. The efferent projections of the fast (Df) and the slow (Ds) depressor motoneurons project into the same areas. Three groups of trichoid sensilla located on the coxal and trochanteral cuticular walls have central contralateral projections and in one case intersegmental projections. All sensory projections terminate either just lateral of or in the Ventral Association Centre (VAC). Comparisons with the mechanoreceptors of other insects reveal similar projection patterns for some proprioceptors and non-homologous central configurations for others. PMID- 4031849 TI - Donor-recipient interconnections between giant nerve fibers in transplanted ventral nerve cords of earthworms. AB - Twelve segments of ventral nerve cord (VNC) from donor earthworms, Eisenia foetida, were transplanted into recipient worms from which a comparable length of VNC had been removed. Within the first few days after transplantation, bud-like formations, containing outgrowths of the giant nerve fibers, were evident at the ends of transplanted and recipient VNC. Morphological and electrophysiological evidence indicated that by 4-10 days after transplantation, medial (MGF) and lateral (LGF) giant fibers within the transplanted VNC formed cell-specific connections with their counterparts in the recipient VNC. Although the diameters of the giant fiber connections in the transplant-recipient junctions were often larger than normal, spike conduction across the junction was initially slow (approximately 1.0 m/s) but gradually increased over the next 2-3 weeks. Within the transplant, giant fibers were initially normal in appearance, but spike conduction was slow (1-2 m/s). During the next few weeks velocities increased by as much as fourfold and then stabilized for the next several months. However, by 4-5 weeks after transplantation, giant fiber morphology within the transplant was altered significantly, as indicated by the formation of numerous branch-like extensions along the length of each giant fiber. By 9-10 months there were further morphological changes in the transplant, as indicated by decreased branching of the giant fibers and altered neuropile. Despite these morphological changes, through-conduction of giant fiber spikes remained reliable. PMID- 4031850 TI - Restoration of sensory and motor function in earthworm escape reflex pathways following ventral nerve cord transplantation. AB - Twelve segments of earthworm ventral nerve cord (VNC) were excised from either segments 10-22 (i.e., within the MGF sensory field) or segments 75-87 (i.e., within the LGF sensory field) in donor worms and heterotopically, or homotopically, transplanted into recipient animals. Morphological evidence indicated that by four days after transplantation, peripheral connections were formed between the transplanted VNC and the body wall of the recipient, many of these connections involving novel pathways projecting ventrally from the transplant. Restoration of giant fiber touch sensitivity in the transplant occurred from 4-14 days after transplantation. Regardless of the site of transplantation, the restored sensitivity (i.e., MGF versus LGF sensory field) always reflected the origin of the donor VNC. Restoration of MGF-mediated motor activity in the transplant occurred approximately 17-22 days after transplantation. In the case of heterotopic transplants (i.e., anterior VNC into posterior segments), the restored MGF-mediated muscle potentials were facilitating, indicating at least some tendency for persistence of this feature after transplantation. Behavioral observations suggested that reconnections involving other reflex pathways (e.g., those controlling setal movements and peristaltic locomotion) were made within the transplant region and that properties of the restored reflexes reflected those of the donor VNC. The rapid restoration of sensory and motor connections, despite heterotopic placement, indicates a significant capacity for peripheral regeneration by the transplanted VNC. On the other hand, the maintenance of various properties of reflex function, despite heterotopic transplantation, suggests a limited capacity for rearrangement of established central connections in the transplanted VNC. PMID- 4031851 TI - Innervation of the limb accessory flexor muscle in several decapod crustaceans. I. Anatomy. AB - The innervation of the accessory flexor muscle of the limbs of several decapod crustaceans was studied by means of vital staining, with methylene blue and electron microscopy. Three patterns of innervation were found. In the first pattern, the distal (DAFM) and proximal (PAFM) heads of the accessory flexor muscle were supplied by two axons (a thick and a thin) which travel in a private nerve along the length of the merus. This pattern was found in the crab (Cancer) and the lobster (Homarus), and conforms to the classical pattern established in the literature. In the second pattern, the nerve to the DAFM is made up of conjoined branches of the flexor and accessory flexor nerves. Consequently, the DAFM receives at least five axons in the portunid crabs, Carcinus, Callinectes, and Ovalipes, and occasionally six axons in Ovalipes. The PAFM in those portunids receives the usual two axons. In the third pattern, based on preliminary observations on the grapsid crab, Pachygrapsus, "super-innervation" of the accessory flexor muscle appears to include not only five axons to the DAFM but also at least three to the PAFM. In all species, methylene blue staining of the axon terminations revealed a regular pattern of blebs which are thought to correspond to synaptic terminals as revealed by electron microscopy. PMID- 4031852 TI - Central and peripheral neurosecretory pathways to an insect flight motor nerve. AB - Ultrastructural examination of the IIN1b nerve to the dorsal longitudinal flight muscle of Manduca sexta L. verified the presence of neurosecretory processes. Subspherical and irregular vesicles were found where the nerve enters the muscle, while spherical vesicles were found in the proximal region only. A dorsal unpaired median (DUM) cell, the median nervous system, and two or more peripheral cells are the sources of these neurosecretory inclusions. Light the electron microscopy CoCl2 backfills of the transverse nerve produced intensification of a peripheral neuron (#1) and processes in nerves IIN1a and IIN1b. Similar backfills of nerve IIN1b produced intensification of a DUM cell, a second peripheral neuron (#2), and processes in the transverse nerve and nerve IIN1a. Neuron #1 contained large spherical electron-dense vesicles while neuron #2 contained smaller subspherical vesicles. These cells were situated upon the link and/or transverse nerves. Based on these results, we suspect central and peripheral neurosecretory processes reach nerve IIN1b as follows: the link nerve projects prothoracic median nervous system and neuron #2 processes, nerve IIN1a projects neuron #1 processes, and nerve IIN1 projects mesothoracic DUM cell processes, although this latter pathway was less clear. PMID- 4031853 TI - Neurological mutation characterized by dysmyelination in NCTR-Balb/C mouse with lysosomal lipid storage disease. AB - Morphological and biochemical studies were performed on the CNS of neurologically affected NCTR-Balb/C mouse. Histological and electron microscopic techniques demonstrated severe myelin deficiency in the affected brains. Neither the presence of lipid-containing macrophages nor reactive gliosis was apparent. Analysis of myelin-associated lipids and proteins revealed prominent depletion of galactocerebroside, sulfatide, and proteolipid proteins. In contrast to the scarcity of myelin-specific constituents a marked accumulation of GM2 and GM3 gangliosides and several neutral glycolipids, i.e., glucocerebroside, lactosylceramide, gangliotriaosylceramide, and gangliotetraosylceramide were found in affected CNS. These abnormalities were already apparent in 12-day-old pups as well as in 65-day-old mice. A significant deficit in the proportion of long-chain fatty acids (C24), notable in both normal and alpha-hydroxy acids of cerebrosides from affected white matter, was measured. The lack of reactive gliosis, the observed depletion of galactocerebroside and sulfatide at the early age of 12 days, and the relative decrease in long-chain fatty acids in affected CNS strongly suggest a defect in myelinogenesis in this mutant rather than a secondary process of myelin breakdown. PMID- 4031854 TI - Characterization of human brain S100 protein fraction: amino acid sequence of S100 beta. AB - Two major components of human brain S100 fraction were purified by HPLC and an amino acid sequence was elucidated for the S100 beta component. Human S100 proteins showed absorption spectra and amino acid compositions similar to S100 alpha and S100 beta from bovine brain. However, the relative amounts of the human proteins were 4% S100 alpha and 96% S100 beta by weight, while the bovine protein distribution was 47% S100 alpha and 53% S100 beta by weight. An amino acid sequence of human S100 beta was established by analysis of overlapping fragments generated by cyanogen bromide and trypsin cleavage. Three amino acid sequence differences between the human and bovine S100 beta were found at residues 7, 62, and 80. These differences were chemically conservative and compatible with minimum single base changes in the codon structures. These results document that S100 beta is a conserved protein among mammals and provide the necessary foundation for current clinical studies. PMID- 4031855 TI - Norepinephrine turnover in the hypothalamus of adult male rats: alteration of circadian patterns by semistarvation. AB - Norepinephrine (NE) turnover, as estimated by 3-methoxy-4 hydroxyphenylethyleneglycol concentration, was studied in the mediobasal hypothalamus of control and semistarved adult male rats at eight time points of a 24-h period. The marked circadian periodicity of NE turnover with a peak in the dark phase in control rats is completely suppressed in semistarved rats. The average 24-h concentration of the NE precursor tyrosine in brain and of tyrosine flow into brain (calculated from plasma amino acid concentrations) is reduced in semistarved rats, but both brain tyrosine and tyrosine flow show continuing circadian fluctuations. PMID- 4031856 TI - Reduction of muscarinic acetylcholine receptor number and affinity by an endogenous substance. AB - We examined the soluble fraction from homogenates of 12-day embryonic chick heart for the presence of an endogenous modulator of muscarinic acetylcholine receptors (mAChR). Homogenates were separated into 100,000 g soluble and crude membrane fractions by differential centrifugation. Aliquots of membranes were incubated in the presence or absence of the soluble fraction and the muscarinic antagonist, [3H]quinuclidinyl benzilate ( [3H]QNB), and the data subjected to Scatchard analysis. In the presence of the soluble fraction, mAChR number decreased up to 70% and the affinity for [3H]QNB decreased six- to eightfold. These results suggested that an endogenous soluble factor (ESF) affected cholinergic ligand binding to the receptor. The amount of ESF extracted from less than 10 mg of brain was sufficient to reduce by 50% [3H]QNB binding to 50 fmol mAChR. ESF activity was partially purified by heat and acid treatment. The loss of receptors was dependent upon the amount of ESF added and was time dependent. QNB protected some receptors from loss due to ESF. The change in mAChR affinity for [3H]QNB was observed only if ESF was present continuously during the [3H]QNB binding assay. Ultrafiltration and gel filtration showed that ESF was less than 10,000 daltons and probably less than 700 daltons. ESF activity was blocked by EDTA. However, ESF was not a divalent cation since it was base labile, and removal of divalent cations with Chelex-100 did not inhibit ESF activity. ESF activity was also blocked by catechol, catecholamines, ascorbate, and dithiothreitol. ESF was present in embryonic but not in adult heart. PMID- 4031857 TI - Morphine-induced changes in histamine dynamics in mouse brain. AB - The effect of the acute morphine treatment on histamine (HA) pools in the brain and the spinal cord was examined in mice. Morphine (1-50 mg/kg, s.c.) administered alone caused no significant change in the steady-state levels of HA and its major metabolite, tele-methylhistamine (t-MH), in the brain. However, depending on the doses tested, morphine significantly enhanced the pargyline (65 mg/kg, i.p.)-induced accumulation of t-MH and this effect was antagonized by naloxone. A specific inhibitor of histidine decarboxylase, alpha fluoromethylhistidine (alpha-FMH) (50 mg/kg, i.p.), decreased the brain HA level in consequence of the almost complete depletion of the HA pool with a rapid turnover. Morphine further decreased the brain HA level in alpha-FMH-pretreated mice. Morphine administered alone significantly reduced the HA level in the spinal cord, an area where the turnover of HA is very slow. These results suggest that the acute morphine treatment increases the turnover of neuronal HA via opioid receptors, and this opiate also releases HA from a slowly turning over pool(s). PMID- 4031858 TI - Glutamate decarboxylase activities in single vertebrate neurons. AB - An enzymatic microassay method for glutamate decarboxylase (GAD) and gamma aminobutyric acid (GABA) was improved to a degree yielding high sensitivity and low blank. Single cell bodies of anterior horn cells and dorsal root ganglion cells were dissected out from the freeze-dried sections of rabbit and chicken spinal cords and Purkinje cell bodies from those of rabbit cerebellum. A minute amount of GABA, present in single neurons or synthesized by GAD in single neurons, was enzymatically converted to NADPH. The NADPH was amplified 10,000 350,000-fold and measured, using an enzymatic amplification reaction (NADP cycling). GAD was contained in all Purkinje cell bodies and its average activity was four- to fivefold higher than those of the molecular and granular layers of rabbit cerebellum. The GABA concentration was threefold higher in Purkinje cell bodies than in these layers. GAD activity, at a level similar to that in the cerebellar layers, was found in almost all the cell bodies of anterior horn cells from rabbit and chicken. GABA was detected in 40% of rabbit neurons and not in chicken neurons. Dorsal root ganglion cells from both species contained no measurable GAD or GABA. PMID- 4031859 TI - gamma-Aminobutyric acid metabolism and behavioral effects after intraventricular injection of spermine in chicks. AB - Effects of intraventricularly injected spermine on behavior and electrocortical activity and gamma-aminobutyric acid (GABA) metabolism after a single dose of 1.13 mumol/animal were studied. Decrease in locomotor activity, sedation or sleep, and electrocortical synchronization that lasted approximately 2 h were observed. In addition spermine caused a significant increase in GABA content in diencephalon and brainstem, 30 min after administration. Concomitantly a significant increase of glutamate decarboxylase (GAD) activity was observed in cerebral hemispheres, diencephalon, and brainstem. Reduction in gamma aminobutyrate: alpha-oxoglutarate amino-transferase (GABA-T) levels occurred in the diencephalon along with a significant increase of GABA-T in the brainstem. The present results demonstrate that spermine has the capacity to affect GABA metabolism and are in favor of the suggestion that endogenous polyamines may modulate GABAergic mechanisms. PMID- 4031860 TI - Biogenic aldehydes in brain: characteristics of a reaction between rat brain tissue and indole-3-acetaldehyde. AB - When indole-3-acetaldehyde was incubated with rat brain tissue, an aldehyde dehydrogenase-independent irreversible disappearance of the aldehyde was found. This was accompanied by an increase in absorbance at 240-400 nm, with a peak at 310 nm. The results suggested that this change in absorbance was caused by a membrane-bound nonenzymatic reaction between indole-3-acetaldehyde and phospholipids. A similar reaction occurred between indole-3-acetaldehyde and pure preparations of phosphatidylethanolamine and phosphatidylserine, but not phosphatidylcholine. Indole-3-acetaldehyde levels also decreased slightly when incubated with albumin but absorbance at 310 nm was unaltered. It is suggested that nonenzymatic reactions between indole-3-acetaldehyde (or other biogenic aldehydes) and membrane components might occur in vivo, and could be involved in the effects of drugs such as ethanol and barbiturates. PMID- 4031861 TI - Purification and characterization of a neuropeptide-degrading aminopeptidase from human brain. AB - The major aminopeptidase from human post-mortem brain (occipital cortex) was purified to homogeneity (as judged by polyacrylamide gel electrophoresis) by anion-exchange chromatography (two steps) and gel filtration (two steps). The molecular weight of the enzyme was estimated as 105,000 from gel filtration. Maximum activity was obtained in the presence of 0.5 mM Ca2+ and 1 mM 2 mercaptoethanol at pH 7.3. Enzyme activity was lost on freezing and thawing or on lyophilization. The enzyme was inhibited by metal-ion chelating agents, sulphydryl blocking agents, bestatin, and puromycin. A series of amino acyl-7 amido-4-methylcoumarins was hydrolysed by the enzyme, with the alanyl derivative being hydrolysed most rapidly (Km 170 microM). Specificity studies with a series of alanine dipeptides suggested that a hydrophobic second residue favoured hydrolysis. Several naturally occurring neuropeptides, including Leu5-enkephalin (Km 180 microM), cholecystokinin octapeptide, and Arg8-vasopressin, were hydrolysed by the aminopeptidase. In a series of opioid peptides, increasing chain length led to decreased susceptibility to hydrolysis. Sulphation of the Tyr1 residue of Leu5-enkephalin and the Tyr2 residue of cholecystokinin octapeptide made the peptides more resistant to hydrolysis. PMID- 4031862 TI - Rat brain phosphatidyl-N,N-dimethylethanolamine is rich in polyunsaturated fatty acids. AB - Phosphatidyl-N,N-dimethylethanolamine (PDME), an intermediate in the formation of phosphatidylcholine (PC) by the sequential methylation of phosphatidylethanolamine (PE), was purified from rat brain and its fatty acid (FA) composition compared with those of brain PC and PE. The proportion of polyunsaturated fatty acids (PUFAs) in the PDME (29.8%) was similar to that of PE (27.7%) and much greater than in PC (2.8%). Like the PUFAs of PE, the major PUFAs found in PDME were arachidonic acid (20:4) and docosahexaenoic acid (22:6). An isotopic method was developed to quantify the PDME purified from brain; a tritiated methyl group from CH3I was transferred to the PDME in the presence of cyclohexylamine to form [3H]PC, and the radioactivity of the PC was then counted. The concentration of rat brain PDME obtained using this method (33.0 +/- 1.8 micrograms/g brain) was very similar to that obtained using quantitative GLC analysis of its FAs (36.9 +/- 1.8 micrograms/g). The FAs in the PE and PC of rat brain synaptosomes were also analyzed; too little PDME was present in synaptosomes to permit similar analysis. The percentage of unsaturated FAs insynaptosomal PE was even higher (43.4 vs. 27.7) than that in PE prepared from whole brain. Since synaptosomes have a very high activity of phosphatidyl-N methyltransferase, the enzyme complex that methylates PE to form PC, this enzyme may serve, in nerve endings, to produce a particular pool of PC, rich in PUFAs, which may have a distinct physiological function. PMID- 4031863 TI - Decreased cerebrospinal fluid glutamine levels in patients with benign brain tumors. AB - CSF glutamine concentrations were studied in 12 patients with benign brain tumors (meningioma, craniopharyngioma, or osteofibroma), 12 patients with malignant brain tumors (astrocytoma, medulloblastoma, pinealoblastoma, or chondrosarcoma), 9 patients with noncerebral tumors, and a reference group of 24 patients. The mean +/- SD levels in the benign tumor group (424 +/- 124 microM) were significantly lower (p less than 0.0004) than those in the reference group (642 +/- 195 microM). There was no significant difference between the CSF glutamine concentrations in the malignant cerebral tumor group (643 +/- 210 microM) or noncerebral tumor group (599 +/- 127 microM) and those in the reference group. In patients with benign brain tumors there was indication of an inverse linear relationship between the logarithm of CSF glutamine concentration and tumor diameter. PMID- 4031864 TI - Binding of [3H]serotonin to skeletal muscle actin. AB - We previously observed that the neurotransmitter 5-hydroxytryptamine (5-HT, serotonin) binds with high- and low-affinity interactions to an actin-like protein prepared from rat brain synaptosomes. In this study, we examined its binding to highly purified actin obtained from rabbit skeletal muscle. Monomeric G-actin bound serotonin with high and low affinities, exhibiting equilibrium dissociation constants (KD values) of 5 X 10(-5) M and 4 X 10(-3) M, respectively. The serotonin binding site on actin was distinct from those sites previously characterized for divalent cations, nucleotides, and cytochalasin alkaloids. The binding of serotonin (1 microM) to G-actin was increased as much as 26-fold by divalent cations. Potassium iodine (KI) increased the affinity of G actin for serotonin, KD values for this binding being 3 X 10(-7) M and X 10(-5) M. Serotonin bound with even higher affinity to polymerized F-actin, with KD values of 2 X 10(-8) M and 2 X 10(-5) M. However, the total number of binding sites on F-actin was only about 4% of the number of G-actin. The binding of serotonin (0.1 microM) to G-actin could be inhibited by phenothiazines (1 microM) or reserpine (10 microM), but not by classical antagonists of serotonin receptors or by drugs that release serotonin or inhibit its uptake. The binding of serotonin to actin in vivo may participate in a contractile process related to neurotransmitter release. PMID- 4031865 TI - Association of serotonin, dopamine, or noradrenaline with an actin-like component in pheochromocytoma (PC12) cells. AB - A rat pheochromocytoma (PC12) cell line was used to examine the possibility that 5-hydroxytryptamine (serotonin), 3,4-dihydroxyphenylethylamine (dopamine), or noradrenaline may be associated with cytoplasmic actin, as was suggested by previous in vitro binding studies on an actin-like protein from rat brain synaptosomes. When PC12 cells were incubated with [3H]serotonin. [3H]dopamine, or [3H]noradrenaline for 30 min at 37 degrees C, approximately 2-4% of the radioactivity present in the cells was found to be associated with a high molecular-weight (actin-like) component in supernatant fractions. Evidence relating this monoamine binding component to actin filaments includes: (a) its strong absorption by myosin filaments at low ionic strength: (b) a decrease in its affinity for myosin in the presence of 1 mM ATP, which lowers the affinity of authentic actin for myosin: (c) displacement of bound [3H]serotonin from it by DNase I, which binds strongly to actin and which inhibits [3H]serotonin binding to actin in vitro; (d) an increase in its binding of each monoamine (by 25-40%) after PC12 cells were preincubated with 10 microM cytochalasin B (a drug that induces depolymerization of F-actin). These findings suggest that serotonin, dopamine, or noradrenaline may associate with actin filaments in vivo. PMID- 4031866 TI - Does phospholipid methylation play a role in the primary mechanism of action of nerve growth factor? AB - Nerve growth factor (NGF)-untreated (naive) and neurite-bearing NGF-treated ("primed") PC12 rat pheochromocytoma cells were used as model system to study the role of phospholipid methylation in the NGF mechanism of action. The neurite bearing cultures were deprived of NGF for 3 h before experimentation. Under both experimental conditions, the cells were labelled with [methyl-3H]methionine and then challenged with NGF for time periods ranging from 5 s to 30 min. Methylated phospholipids were extracted and then resolved and identified by TLC as phosphatidyl mono-, di-, and trimethyl ethanolamine. Quantification of the amount of radioactivity incorporated into each of the phospholipids indicated that NGF does not significantly alter phospholipid methylation either in naive or in neurite-bearing cells. Furthermore, using a methyltransferase inhibitor, it was found that neurite outgrowth still occurs when phospholipid methylation is almost completely blocked. These results indicate that phospholipid methylation does not play a primary role in the mechanism of action of NGF. PMID- 4031867 TI - Circadian rhythm in pineal N-acetyltransferase activity: phase shifting by dark pulses (III). AB - N-Acetyltransferase (NAT) is an enzyme whose rhythmic activity in the pineal gland and retina is thought to be responsible for melatonin circadian rhythms. The enzyme has circadian properties--its rhythm persists in constant conditions, and it is precisely controlled by light and dark. Experiments are reported in which 4-h light or dark pulses were imposed on chicks (Gallus domesticus) over a 24-h period. Pineal NAT profiles were measured during and subsequent to the pulses. The phase of the NAT cycle following pulses was plotted to obtain phase response curves. Light pulses produced a maximum phase shift (advance of 5 h) 8 h after the expected time of lights-out; dark pulses produced a maximum phase shift (advance of 4 h) 3 h after the expected time of lights-out. Maximum phase delays (-2 h) occurred 1-2 h after the expected lights-out for light pulses and 8 h after expected lights-on for dark pulses. PMID- 4031868 TI - Specific replacements of pyruvate for trophic support of central and peripheral nervous system neurons. AB - When embryonic central nervous system neurons are seeded at low densities with Eagle's basal medium supplemented with the serum substitute N1, glucose, and glutamine, neuronal survival for even 24 h requires the additional supply of exogenous pyruvate--and so does the survival of many peripheral nervous system neurons. Pyruvate can be replaced by alpha-ketoglutarate or oxaloacetate, but not by Krebs cycle substrates that are not keto acids. Most other alpha-keto acids tested (though not beta- or gamma-keto acids) also mimic pyruvate. The apparent equivalence to pyruvate of all these compounds includes identical ED50 values (300 microM for embryonic avian fore-brain neurons, 30-40 microM for rat hippocampal neurons), and also identical susceptibilities to the pyruvate-sparing effects of other low-molecular-weight agents present in Dulbecco's modified Eagle's medium or in astroglia conditioned medium. The substitute alpha-keto acids, however--unlike pyruvate, alpha-ketoglutarate, or oxaloacetate--support cell survival only in the presence of alpha-amino acids that transaminate to alpha-ketoglutarate, oxaloacetate, or pyruvate. The alpha-keto acids, therefore, operate as acceptors of amino groups from appropriate donors to generate Krebs cycle-relevant substrates. Consistent with this view, [14C]glutamate did not generate appreciable 14CO2 unless accompanied by a suitable alpha-keto acid.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4031869 TI - Inhibition of monoamine oxidase by phenyl azides. AB - We had previously shown that 4-fluoro-3-nitrophenyl azide (FNPA) is a competitive inhibitor of both types of monoamine oxidase (MAO) in the dark, but it is a preferential photoaffinity label for only the type B MAO (MAO-B). Recently we synthesized a number of arylazido compounds with structures related to FNPA and determined the effects of these compounds on the two types of MAO in rat brain cortex. We found that the fluoro group of FNPA was not required for the inhibition of MAO activities because neither the presence nor the position of the fluoro group affected its inhibition of MAO. On the other hand, both the nitro and the azido groups of FNPA were shown to be important for FNPA inactivation of two types of MAO. The inhibitory potency was significantly lower for compounds without either group. Furthermore, we found that all nitrophenyl azide isomers except 2-nitrophenyl azide were photodependent inhibitors of MAO-B. Under the same experimental conditions none of the compounds photoinactivated MAO-A. On the basis of these findings, mechanisms for FNPA inhibition of the two types of MAO are discussed. PMID- 4031870 TI - 1-Piperideine as an in vivo precursor of the gamma-aminobutyric acid homologue 5 aminopentanoic acid. AB - Intraperitoneal injection of the cyclic imine 1-piperideine in mice resulted in measurable quantities of 5-aminopentanoic acid in brain. 5-Aminopentanoic acid is a methylene homologue of gamma-aminobutyric acid (GABA) that is a weak GABA agonist. 5-Aminopentanoic acid formed in the periphery was ruled out as the source of brain 5-aminopentanoic acid based on the absence of detection in brain following injection of 100 mg/kg of 5-aminopentanoic acid. Deuterium-labeled 1 piperideine was prepared by exchange in deuterated phosphate buffer. Injection of [3.3-2H2]1-piperideine yielded [2.2-2H2]5-aminopentanoic acid in brain. The results are consistent with uptake of 1-piperideine into brain and oxidation of the precursor to 5-aminopentanoic acid. Inhibition of GABA catabolism by pretreatment with aminooxyacetic acid increased brain concentrations of 5 aminopentanoic acid formed from 1-piperideine, suggesting that 5-aminopentanoic acid is an in vivo substrate of 4-aminobutyrate:2-oxoglutarate aminotransferase. PMID- 4031871 TI - Facilitated transport of glucose from blood into peripheral nerve. AB - D-Glucose is the major substrate for energy metabolism in peripheral nerve. The mechanism of transfer of glucose across the blood-nerve barrier is unclarified. In this study an in situ perfusion technique was utilized, in anesthetized rats, to examine monosaccharide transport from blood into peripheral nerve. Unidirectional influxes of D-[14C]glucose, L-[14C]glucose, and [14C]3-O-methyl-D glucose across capillaries of the tibial nerve were measured at different perfusate concentrations of unlabelled D-glucose. The permeability-surface area product (PA) for D-[14C]glucose and [14C]3-O-methyl-D-glucose decreased, whereas the PA for L-[14C]glucose remained constant, as the perfusate concentration of D glucose was increased. In the presence of no added unlabelled D-glucose in the perfusate, the PA for L-[14C]glucose equaled one-fifth the PA for D-[14C]glucose. These results demonstrate self-saturation, competitive inhibition, and stereospecificity of glucose transfer, and for the first time show a unidirectional facilitated transport mechanism for D-monosaccharides at capillaries of mammalian peripheral nerve. The data were fit to a model for facilitated transport and passive diffusion. The half-saturation constant and maximal rate of transport for the saturable component of D-glucose influx equaled 23 +/- 11 mumol X ml-1 and 6.6 +/- 3.2 X 10(-3) mumol X s-1 X g-1, respectively. The constant of nonsaturable glucose influx equaled 0.5 +/- 0.1 X 10(-4) s-1. At normal plasma glucose concentrations, the saturable component comprises about 80% of total D-glucose influx into nerve.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4031872 TI - Alteration in the postnatal ontogeny of cerebellar norepinephrine content following chronic prenatal carbon monoxide. AB - The postnatal ontogeny of norepinephrine content in the cortex and cerebellum was determined in rats exposed prenatally to a chronic low level of carbon monoxide (150 parts per million). In the cerebellum, norepinephrine concentration and total norepinephrine content among carbon monoxide-exposed rats were consistently elevated over that of control rats from the second through the sixth postnatal weeks. In the cortex, norepinephrine concentration and total norepinephrine content among carbon monoxide-exposed rats did not differ from that of control rats over the same period. These results identify the cerebellum as a region whose postnatal development is altered by prenatal exposure to low levels of carbon monoxide-induced hypoxia. PMID- 4031873 TI - Synthesis of the novel dipeptide beta-aspartylglycine by Aplysia ganglia. AB - Isolated ganglia from Aplysia californica rapidly took up [14C]glycine or [14C]aspartate from a sea-water medium. Approximately 20% of the tissue radioactivity was recovered in the peptides beta-aspartylglycine and glutathione after incubation with [14C]glycine. Compared with other individual cells isolated from the abdominal ganglion, the glycine-containing white cells (R3-R14) incorporated less [14C]glycine into beta-aspartylglycine, but similar amounts into glutathione. In contrast, [14C]aspartate was metabolized primarily to nonamino dicarboxylic acids and relatively little radioactivity was incorporated into beta-aspartylglycine. PMID- 4031874 TI - Kinetic analysis of cerebrovascular isoleucine transport from saline and plasma. AB - The concentration dependence of regional isoleucine transport across the blood brain barrier was determined in anesthetized rats with the in situ brain perfusion technique of Takasato et al. [Am. J. Physiol. 247, H484-493 (1984)]. This technique allows, for the first time, accurate measurements of cerebrovascular amino acid transport in the absence of competing amino acids using saline perfusate, and in the presence of physiological concentrations of amino acids using plasma perfusate. Cerebrovascular isoleucine transport from saline perfusate followed Michaelis-Menten saturation kinetics where Vmax = 9 - 11 X 10(-4) mumol X s-1 X g-1 and Km = 0.054-0.068 mumol X ml-1 in six brain regions. A component of nonsaturable transport was not detected in any brain region even though perfusate isoleucine concentration was increased to greater than or equal to 150 times the normal plasma concentration. Isoleucine influx during plasma perfusion was only 8% of that predicted from the saline perfusion data due to transport inhibition by competing amino acids in plasma. Competitive inhibition increased the apparent Km for isoleucine transport from plasma by greater than or equal to 24-fold to 1.5-1.7 mumol X ml-1. These data provide accurate new estimates of the kinetic constants that describe amino acid transport across the blood-brain barrier. In addition, they indicate that the cerebrovascular transfer-site affinity (1/Km) for isoleucine is approximately fivefold greater than previously reported with the brain uptake index technique. PMID- 4031875 TI - Effect of unilateral decortication on choline acetyltransferase activity in the nucleus basalis and other areas of the rat brain. AB - Acetyl-coenzyme A: choline O-acetyltransferase (EC 2.3.1.6) (ChAT) enzyme activity was measured in the nucleus basalis and other microscopically identified brain areas at various times after unilateral cortical lesions were made in the rat. Initially, a significant decrease in ChAT activity was detected in the nucleus basalis ipsilateral to the lesion. However, after 120 days ChAT activity had apparently recovered, as levels of the enzyme at that time were not significantly different from control values. No changes in ChAT activity could be detected in any of the other brain areas similarly studied. The significance of these findings and their relationship to the morphological changes seen in neurones of the nucleus basalis after cortical lesions are discussed. PMID- 4031876 TI - Choline acetyltransferase activity in the rat trigeminal system. AB - Choline acetyltransferase activity was investigated in the superior cervical ganglia and in six microdissected regions of the medulla oblongata of the rat ipsilateral and contralateral to electrolytic lesions of the trigeminal sensory ganglia (Gasserian). Electrolytic lesions of the Gasserian ganglia failed to modify levels of enzymatic activity in all structures studied. This result would be an argument against the existence of a major cholinergic population of sensory neurones in the trigeminal system. PMID- 4031877 TI - Circannual rhythm of free fatty acids and diacylglycerols in 5-day-old rat cerebrum during pentylenetetrazol-induced convulsions. AB - Free fatty acids (FFA) and diacylglycerol (DG) content and composition in the cerebrum of 5-day-old rats were studied after pentylenetetrazol (PTZ)-induced convulsions. A threefold increase in brain FFA was observed 30 min after PTZ injection in experiments carried out in spring. In contrast, a 50% decrease in FFA content was observed during summer. These changes were accounted for by saturated and monoenoic fatty acids, whereas arachidonic and docosahexaenoic acids were not affected during the convulsive episode in either season. The effect of PTZ on brain DG was much smaller than it was on FFA, and less sensitive to seasonal influence. However, DG released in the summer was significantly less enriched in arachidonic acid than in the spring. Levels of FFA and DG in untreated animals were found to be subject to a circannual rhythm. Both the levels of FFA and their degree of unsaturation (unsaturated fatty acids/total FFA) were highest in summer and lowest in winter, whereas the opposite was true for DG. Circannual variations in these metabolites may be the manifestation of a programmed biological calendar regulating enzymes of brain lipid metabolism in homeotherms that under natural conditions must adapt to changing environmental temperatures. PMID- 4031878 TI - [3H]Threo-(+/-)-methylphenidate binding to 3,4-dihydroxyphenylethylamine uptake sites in corpus striatum: correlation with the stimulant properties of ritalinic acid esters. AB - Saturable and stereoselective binding sites for [3H]threo-(+/-)-methylphenidate were characterized in rat brain membranes. The highest density of [3H]threo-(+/-) methylphenidate binding sites was found in the synaptosomal fraction of corpus striatum. Scatchard analysis revealed a single class of noninteracting binding sites with an apparent dissociation constant (KD) of 235 nM and a maximum number of binding sites (Bmax) of 13.4 pmol/mg protein. Saturable, high-affinity binding of [3H]threo-(+/-)-methylphenidate to striatal synaptosomal membranes was dependent on the presence of sodium ions. A good correlation (r = 0.88; p less than 0.001) was observed between the potencies of various psychotropic drugs in displacing [3H]threo-(+/-)-methylphenidate from these sites and their potencies as inhibitors of [3H]3,4-dihydroxyphenylethylamine ( [3H]dopamine) uptake into striatal synaptosomes. A good correlation (r = 0.85; p less than 0.001) was also observed between the potencies of a series of ritalinic acid esters in inhibiting [3H]threo-(+/-)-methylphenidate binding to striatal synaptosomal membranes and their potencies as motor stimulants in mice. These observations suggest that the binding sites for [3H]threo-(+/-)-methylphenidate described here are associated with a dopamine uptake or transport complex, and that these sites may mediate the motor stimulant properties of ritalinic acid esters such as methylphenidate. PMID- 4031879 TI - Cholinergic- and adrenergic-stimulated inositide hydrolysis in brain: interaction, regional distribution, and coupling mechanisms. AB - Carbachol and norepinephrine were used as agonists to compare and contrast cholinergic and adrenergic stimulation of inositide breakdown in rat brain slices. Carbachol acts through a muscarinic (possibly M1) receptor and norepinephrine acts through an alpha 1 adrenoceptor. Studies in cerebral cortical slices indicated that both agonists stimulated the production of inositol-1 phosphate and glycerophosphoinositol. Although the initial rates for the stimulation of inositol phosphate release were similar for the two ligands, the response to norepinephrine continued for 60 min and was larger compared with carbachol which plateaued at 30 min. The presence of carbachol did not affect the ED50 for norepinephrine. Concentrations of carbachol near the ED50 in combination with norepinephrine resulted in an additive response whereas maximal concentrations of carbachol and norepinephrine resulted in a less than additive response in the cortex. This negative interaction was also seen in the hippocampus and hypothalamus but not in the striatum, brainstem, spinal cord, olfactory bulb, or cerebellum. Norepinephrine had a larger response than carbachol in the hippocampus, striatum, and spinal cord, but the reverse was true in the olfactory bulb. Manganese (1 mM) stimulated the incorporation of [3H]inositol into phosphatidylinositol (PtdIns) four- to fivefold but not into polyphosphoinositides. The stimulation by manganese of PtdIns labelling increased the nonstimulated release of inositol phosphates but did not affect the stimulated release of inositol phosphates by carbachol or norepinephrine.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4031880 TI - Effect of reactive oxygen species on myelin membrane proteins. AB - Fresh myelin, isolated from brainstems of adult rats, was incubated in the presence of Cu2+ and H2O2. Electrophoretic analysis of the reisolated myelin membrane revealed a gradual loss of the protein moiety from the characteristic pattern and an increase in aggregated material appearing at the origin of the gel. The aggregation of proteins was time-dependent and was concomitant with the accumulation of lipid peroxidation products reactive with thiobarbituric acid. Furthermore, during the course of incubation, there was a gradual decrease in the amount of recovered light myelin and a quantitatively similar increase in heavier myelin subfractions. The aggregation of proteins seems not to be directly related to the buoyant densities of myelin fragments. The peroxidative damage to the myelin proteins may be an important contributor to pathochemistry of myelin sheath, in particular, and in general it implies the susceptibility of the protein moiety of cell membranes to oxygen-induced deterioration. PMID- 4031881 TI - Identification and topography of substrates for protein carboxyl methyltransferase in synaptic membrane and myelin-enriched fractions of bovine and rat brain. AB - The major components of crude brain synaptosomes (synaptic membranes, mitochondria, and myelin) have been separated and analyzed by polyacrylamide gel electrophoresis for the presence of proteins that serve as substrates for protein carboxyl methyltransferase. Of the three fractions, synaptic membranes contain the largest number of individual methyl acceptors (at least seven), while mitochondria contain no well-defined methyl acceptors. Undisrupted myelin contains a single major methyl acceptor with a very low apparent molecular weight. The patterns of protein methylation in synaptic membranes prepared from cerebral cortex, hippocampus, striatum, thalamus, and tectum showed marked differences; however, these differences could largely be explained by differential degrees of myelin contamination in synaptic membranes from the different regions. The effect of trypsin pretreatment on the carboxyl methylation of intact and lysed synaptosomes was studied to estimate the sidedness of the major methylation sites on synaptic membranes. One of the methyl acceptors (Mr 48K) appears to be facing the intracellular surface of the synaptosome, but most sites appear to be outward facing. PMID- 4031882 TI - In vivo phosphorylation of the postsynaptic density glycoprotein gp180. AB - Rats received intraventricular injections of [32P]PO4 and were killed after 30 min for the preparation of postsynaptic densities (PSDs). Gel electrophoretic analysis identified a number of PSD proteins that incorporated 32P under these conditions. Major proteins that were labelled with 32P had Mr of 185,000, 165,000, 140,000, 92,000, and 51,000. Of these p185, p165, and p140 were also labelled when PSDs were incubated with [gamma-32P]ATP in vitro. In contrast p92 and p51 were relatively poorly labelled under in vitro conditions. Analysis of glycoproteins isolated by chromatography on concanavalin A (Con A)-agarose demonstrated that greater than 70-80% of the 32P present in the glycoproteins eluted from Con A-agarose with alpha-methyl-D-mannopyranoside (Con A+ glycoproteins) was associated with the PSD specific glycoprotein gp180 following both in vivo and in vitro labelling. Phosphopeptide maps and phosphoamino acid analysis of gp180 indicated that similar sites were labelled in vitro and in vivo. Analysis of the subcellular distribution of glycoproteins that incorporated 32P during in vivo labelling demonstrated that gp180 was highly concentrated in PSDs, in accord with the previously suggested exclusive association of this glycoprotein with postsynaptic structures. PMID- 4031883 TI - Is propionylcholine present in or synthesized by electric organ? AB - When small blocks comprising four columns of electrocytes were excised from electric organs of Torpedo marmorata after stimulation in vivo via the electric lobe at 1 Hz for 1 h and allowed to recover at 20-22 degrees C for several hours in medium containing 100 microM d4 choline and 500 microM propionate, small quantities of propionylcholine amounting to no more than 1% of the endogenous acetylcholine of the tissue could be detected in tissue extracts by gas chromatography-mass spectrometry (GCMS). Kinetic studies demonstrated that there was no nonexchangeable propionylcholine in the tissue and in the absence of added propionate, propionylcholine levels were less than 0.2% of tissue acetylcholine. Vesicular propionylcholine amounted to less than 0.5% of vesicular acetylcholine and the distribution of d0 and d4 propionylcholine suggested that an appreciable proportion (up to one-third) of this could be an artifact of preparation for GCMS determinations. Propionylcholine formation during extraction and demethylation of an artificial mixture of acetylcholine, choline, and propionate was indeed detected. It is concluded that propionylcholine has no significance as an endogenous or as a false transmitter at this terminal, in conformity with the work of Sheridan et al. [Z. Zellforsch. 74, 281-307 (1966)] but in contrast to the report of O'Regan [J. Neurochem. 39, 764-772 (1982)]. PMID- 4031884 TI - Effects of monovalent ions on the transport of noradrenaline across the plasma membrane of neuronal cells (PC-12 cells). AB - The dependence on Na+, K+, and Cl- of uptake and accumulation of [3H]noradrenaline was studied in plasma membrane vesicles isolated from PC-12 pheochromocytoma cells. Plasma membrane vesicles accumulated [3H]noradrenaline when an inward-directed gradient for Na+ and an outward-directed gradient for K+ were imposed across the vesicle membrane. Under these conditions, initial rates of uptake of [3H]noradrenaline were saturable (Km = 0.14 microM) and inhibited by a series of substrates and inhibitors of "uptake". The IC50 values were positively correlated with those for inhibition of uptake into intact PC-12 cells. Uptake and accumulation of [3H]noradrenaline in plasma membrane vesicles were absolutely dependent on external Na+ and Cl-; they were dependent on an inwardly directed gradient for Na+ but less dependent on an inwardly directed gradient for Cl-. Internal K+ strongly enhanced uptake and accumulation of [3H]noradrenaline. Rb+, but not Li+, had the capacity to replace internal K+. Two explanations are proposed for this effect of internal K+: (a) creation of a K+ diffusion potential (inside negative) provides a driving force for inward transport, and/or (b) K+ increases the turnover rate by formation of a highly mobile potassium-carrier complex. A hypothetical scheme for the transport of noradrenaline is presented. PMID- 4031885 TI - Glycerol phosphate dehydrogenase activity of oligodendrocytes isolated from adult pig brain: its inducibility by hydrocortisone. AB - Developing oligodendrocytes cultured in vitro express glycerol phosphate dehydrogenase (GPDH; EC 1.1.1.8) and are known to respond to glucocorticoid treatment by increased activity of GPDH. We present evidence that GPDH is enriched in white matter and oligodendrocytes of adult pig brain. Bulk-isolated oligodendrocytes maintained in culture for several weeks exhibit an almost constant level of GPDH activity. Furthermore, a 4-day stimulation with hydrocortisone induces GPDH specific activity of long-term cultured oligodendrocytes from adult pig brain. PMID- 4031886 TI - Enzymatic regulation of glycoprotein synthesis in peripheral nervous system myelin. AB - The enzyme UDP-N-acetylglucosamine: dolichyl phosphate, N-acetylglucosamine-1 phosphate transferase initiates the synthesis of the oligosaccharide chain of complex-type glycoproteins. In view of the high content of glycoprotein in peripheral nerve myelin, the properties of this enzyme, its changes with age, and the effect of the specific inhibitor tunicamycin were investigated. The enzyme activity in rat peripheral nerve homogenate was completely dependent on the presence of exogenous dolichyl phosphate as well as Mg2+ and a detergent (Triton X-100) and was also greatly stimulated by a high salt concentration (0.4 M KCl) and AMP. The highest specific activity was present in the postmitochondrial membranes. The specific activity in postmitochondrial membranes in the presence of exogenous dolichyl phosphate reached a maximum at 17 days and remained relatively high throughout development, up to 2 years of age, but the activity was much lower when dolichyl phosphate was not added. This indicates that the enzyme level does not decrease with age, but that the content of the lipid cofactor may limit glycoprotein synthesis in vivo. Tunicamycin (5 micrograms) was injected intraneurally into 24-day-old rat sciatic nerve, and the enzyme was assayed from 1 to 24 days after injection. The specific activity of the transferase remained at low levels (5-40% of the level in control nerve) in most injected nerves assayed throughout this postinjection period. A protein previously identified as the unglycosylated P0 protein was synthesized in vitro by the tunicamycin-injected nerve and could be demonstrated to be incorporated into myelin in large amounts at 2 days and in small amounts at 6 days after injection.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4031887 TI - Electrophoretic analysis of myelin proteolipid protein and its deacylated form. AB - Myelin proteolipid protein is known to contain covalently bound fatty acid. To determine the contribution of the fatty acid to the multiple bands observed on sodium dodecyl sulfate-polyacrylamide gel electrophoresis, the electrophoretic parameters of the proteolipid protein were compared with those of the deacylated form. The relative mobility and proportion of each band, as well as the retardation coefficient and free electrophoretic mobility, were not altered by removal of the fatty acid moiety. Furthermore, the acylated and deacylated forms bound the same amounts of sodium dodecyl sulfate. These data demonstrate that the presence of covalently bound fatty acids does not account for the electrophoretic heterogeneity of the proteolipid. PMID- 4031888 TI - Structure of catecholamine secretory vesicles from PC12 cells. AB - Catecholamine secretory organelles were partially purified from PC12 cells. Measurement of the sedimentation coefficient (540S in 0.32 M sucrose), density in an isoosmotic gradient (1.139 g/cm), and density in an isoosmotic gradient using D2O as a solvent (1.205 g/cm3) have allowed us to calculate the molecular weight (1.17 X 10(9) daltons), radius (74 nm), and water content (62% vol/vol) of the secretory vesicle. The vesicle appears to contain ATP, but the molar ratio of 3,4 dihydroxyphenylethylamine (dopamine) to ATP in the particles is high (16.5) and the ATP was frequently asymmetrically distributed in the vesicle fraction. The particle behaves like a true secretory particle in that the dopamine content of the particle is increased by pargyline, diminished by depolarization, and abolished by reserpine. Sequential purification of PC12 lysates on controlled pore glass columns and isoosmotic Ficoll gradients produced a 20-30-fold purification, but this enrichment is not sufficient to produce a homogeneous population of vesicles. An 82,000-dalton protein copurifies with secretory granules and appears to be the major secreted protein. At this stage of purification this single protein makes up about 30% of the protein in the vesicle containing fractions and so the vesicles must be approaching homogeneity. PMID- 4031889 TI - Acetylcholine synthesis by adult bovine adrenal chromaffin cell cultures. AB - Adrenal chromaffin cells normally synthesize and release catecholamines. In the present study, [3H]acetylcholine synthesis and another characteristic of cholinergic neurons, [3H]choline uptake, were studied in cultures of adult bovine adrenal chromaffin cells. Chromaffin cell cultures took up [3H]choline from the medium and acetylated the [3H]choline to form [3H]acetylcholine. The rate of [3H]acetylcholine synthesis increased after 19 days in culture and continued to increase up to 28 days in culture. [3H]Acetylcholine synthesis could be increased by stimulating the cells with a depolarizing concentration of K+. The ability for K+ to stimulate synthesis of [3H]acetylcholine developed only after 28 days in culture. [3H]Choline was taken up by the cultures through a single mechanism with a high (to intermediate) affinity for choline. [3H]Choline uptake was enhanced by Na+ omission in day-14 cultures, but was at least partially Na+-dependent in day 29 cultures. Hemicholinium-3 (IC50 less than 10 muM) inhibited [3H]choline uptake into chromaffin cell cultures. It is concluded that bovine adrenal chromaffin cells, maintained in culture, are able to exhibit cholinergic properties and this capacity is retained even by the mature adult cell. PMID- 4031890 TI - Distribution of Nsp100 and Nsp100 kinase, a nerve growth factor-sensitive phosphorylation system, in rat tissues. AB - Previous work from this laboratory has shown that in PC12 cells the phosphorylation of a specific soluble protein is decreased by nerve growth factor treatment. The protein, designated Nsp100, and its kinase have been separated and partially purified from PC12 cells. In the present work, the tissue distribution of Nsp100 phosphorylation in 5-day-old and adult rats was studied. In adult rats, phosphorylation of an Nsp100-like protein was observed in brain, adrenal gland, testis, and muscle, but not in liver or kidney. In 5-day-old rats, a similar phosphorylation was observed in brain, adrenal gland, superior cervical ganglia, liver, spleen, kidney, and muscle. In PC12 cells, Nsp100 phosphorylation is completely inhibited by 5 X 10(-5) M Zn2+ and is completely inactivated by treatment at 50 degrees C for 2 min. The phosphorylation of the Nsp100-like protein in both adult and 5-day-old rats showed the same characteristics. Partial purification of Nsp100 and Nsp100 kinase from the brains of 5-day-old rats was carried out using the procedures developed for PC12 cells. Nsp100 and Nsp100 kinase were separated on diethylaminoethyl-Sephacel, and the kinase was eluted with 0.3 M NaCl; the same results have previously been obtained with PC12 cells. Phosphorylated Nsp100 from brain and from PC12 cells was compared by proteolysis on sodium dodecyl sulfate gels; similar peptide patterns were generated from the two samples.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4031891 TI - Isolation of eukaryotic initiation factor 2 from rat brain. AB - Eukaryotic initiation factor 2 (eIF-2) was isolated from salt-washed microsomes of 4-day-old rat brain which show a high rate of protein synthesis. A three-step purification scheme was employed, including heparin-Sepharose, phosphocellulose, and DEAE-cellulose column chromatography. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the isolated factor revealed three polypeptides with molecular weights of 43,000, 54,000, and 59,000 and 90% purity. The rat brain eIF 2 forms ternary complexes with [3H]methionyl-tRNAi and GTP. In terms of specific activity, the purification does not correspond to that revealed by electrophoretic analysis. During purification there is an apparent loss of additional factors that modulates the activity of eIF-2 and explains the high rate of activity of the crude fraction. PMID- 4031892 TI - Involvement of an "antizyme" in the inactivation of ornithine decarboxylase. AB - DL-Allylglycine causes a marked increase in mouse brain ornithine decarboxylase (ODC) activity. The amount of immunoreactive enzyme protein increases concomitantly with the activity, but the enzyme protein decreases more slowly than that of the activity. The amount of immunoreactive ODC in brain is many hundred times that of the catalytically active enzyme. The fact that mouse brain cytosol contains high amounts of dissociable antizyme (an inactivating protein) indicates the existence of an inactive, immunoreactive ODC-antizyme pool. The total antizyme content does not change markedly, but instead there are significant changes in different antizyme pools. Putrescine concentrations start to increase 8 h after treatment with allylglycine and concomitantly with this increase, antizyme is released to inhibit enzyme activity. These results indicate the involvement of antizyme in the inactivation process of ODC. PMID- 4031893 TI - Multiple [35S]t-butylbicyclophosphorothionate binding sites in rat and chicken cerebral hemispheres. AB - Specific binding of [35S]t-butylbicyclophosphorothionate (TBPS) to membranes from cerebral hemispheres of adult rat and chicken was determined over a range of radioligand concentrations from 0.25 to 500 nM. Scatchard plots of these data were curvilinear and nonlinear regression analysis indicated binding to two sites that differ in affinity. For rat cerebrum, KD(1) = 1.15 nM, Bmax(1) = 0.085 pmol/mg; KD(2) = 232 nM, Bmax(2) = 16.9 pmol/mg. For chicken cerebrum, KD(1) = 1.39 nM, Bmax(1) = 0.111 pmol/mg; KD(2) = 166 nM, Bmax(2) = 17.6 pmol/mg. This multiplicity of [35S]TBPS binding was further confirmed when unlabeled TBPS or picrotoxinin displaced radioligand. The displacement curves were biphasic and yielded Hill coefficients from 0.65 to 0.70. These displacement curves were also resolved into two components with distinct IC50 values for unlabeled TBPS (rat, 1.55 and 271 nM; chicken, 2.40 and 224 nM). The IC50 values were similar to the dissociation constants obtained from equilibrium binding measurements. PMID- 4031894 TI - Cell survival characteristics and choline acetyltransferase activity in motor neurone-enriched cultures from chick embryo spinal cord. AB - The effect of muscle extract on cell survival and choline acetyltransferase (ChAT) activity in cultures of enriched cholinergic neurones from 7-day chick embryo spinal cord was examined. When neurones were grown on hydrated collagen gels, considerable cell survival and ChAT activity were obtained even in the absence of tissue extract. These parameters were stimulated twofold in the presence of skeletal muscle extract but not liver or skin extracts. The cholinergic neurotrophic activity was found to be heat- and trypsin-sensitive, nondialysable, and to act in the virtual absence of glial cells. These data are consistent with a retrogradely acting motor neurone trophic activity. PMID- 4031895 TI - [Preparation, stereochemical study and evaluation of the antileukemic activity of glucoside derivatives of (-)-steganol]. AB - The optically active lignan (-)-steganol was prepared from natural (-)-steganacin by selective deacetylation and was transformed, via a three-step sequence, into the corresponding 4', 6'-O-ethylidene- and thenylidene-beta-D-glucopyranosides, 3b and 3c, respectively, which are the analogues, in the steganol series, of the podophyllotoxin derived, and clinically useful, anticancer drugs, VP16-213 and VM26. Formation of the dimeric compound distegyl ether as a minor by-product was established. Complete elucidation of all the asymmetric centres was performed with the help of high resolution 1H-nmr studies at 400 MHz, COSY experiment at 500 MHz and X-ray analysis. Contrary to the podophyllotoxin series, the glycosylation of (-)-steganol occurred with retention of configuration, and all the synthesized compounds, including distegyl ether, exhibited the starting natural R configuration at C-5. PMID- 4031896 TI - Preparation of glucosidic derivatives of steganol. AB - Glucoside derivatives of steganol analogous to the semisynthetic podophyllotoxin derivative, VP 16-213, were prepared. Glucosidation of steganol with 2, 3, 4, 6 tetra-O-benzylglucopyranose gave the alpha-anomer of the glucoside as the major product. Subsequent removal of the benzyl groups and reaction with acetaldehyde dimethyl acetal gave the ethylidene derivative 10. The beta-anomer of the glucoside was similarly converted to 12. All derivatives prepared were screened for activity in the DNA breakage assay. PMID- 4031897 TI - [The effect of modification of the intracellular distribution of polyamines on the proliferation of hepatocytes treated with 2-methyl-9-hydroxyellipticine]. AB - 2-Methyl-9-hydroxyellipticine (MHE) added to tumoral hepatocyte cultures (400 ng MHE/ml medium) is responsible for a cytostatic effect. This decrease of cellular proliferation and of DNA synthesis is accompanied by an increase of intracellular free spermidine levels. We could not attribute this result to a deviation of this polyamine metabolism. These increased concentrations of free spermidine are connected to a decrease of the amount of nuclear bound polyamines, mainly joined with the RNA fraction. Thus, the cytostatic effect observed with this drug might be related to a decrease in the amount of spermidine connected to RNA; therefore, its intercalating effect is only indirectly responsible for the cellular proliferation decrease. PMID- 4031898 TI - Antimicrobially active alkaloids from Tabernaemontana chippii. AB - From Tabernaemontana chippii root bark, forty-five alkaloids were isolated; thirty-four were fully characterized by means of their spectral data and/or co tlc; eight alkaloids were new, four of them being 3-hydroxy derivatives of known dimeric voacamine type alkaloids. Most of the twenty-six known alkaloids belonged to the corynanthean, ibogan, or bisindole classes. The structures of eleven other alkaloids--all minor--were only partially elucidated, most of them being new alkaloids. All the dimeric alkaloids were shown to possess strong antimicrobial activity against gram-positive bacteria and moderate to weak activity against gram-negative bacteria. PMID- 4031899 TI - Constituents of Erysimum inconspicuum. Two sulfur-containing lactone compounds. AB - The alcohol extract of Erysimum inconspicuum fruits, which exhibited cytotoxic activity against the KB cell line and some activity against the P-388 lymphocytic leukemia in vivo, was studied. Strophanthidin, uzarigenin, and two sulfur containing lactones, erysulfone[6-methylsulfonyl-4-hydroxyhexanoic acid lactone] and erysulfoxide[6-methylsulfinyl-4-hydroxyhexanoic acid lactone], were isolated and characterized by spectral data. PMID- 4031900 TI - Antineoplastic and piscicidal 1-alkyldaphnane orthoesters from Pimelea species. AB - Five biologically active daphnane orthoesters have been isolated from Pimelea species (Thymelaeaceae). Four of these possessing antineoplastic activity against in vivo murine P-388 lymphocytic leukemia are gnidimacrin from P. ligustrina, simpleximacrin from P. simplex, linimacrin d and Pimelea factor P3 from P. linifolia. Linimacrin c from P. linifolia and the other four compounds showed piscicidal activity. Gnidimacrin and Pimelea factor P3 have previously been isolated from other members of the Thymelaeaceae. Simpleximacrin and linimacrins c and d are new compounds. PMID- 4031901 TI - On the distribution of ribosome-inactivating proteins amongst plants. AB - The extracts from various parts (mostly seeds) of 56 different plants were examined for inhibition of protein synthesis by a rabbit reticulocyte lysate. Most extracts inhibited protein synthesis with an ID50 (concentration giving 50% inhibition) of 100 micrograms extract protein per ml, or less. The extracts with high activity were partially purified by CM cellulose chromatography. Protein containing fractions were separated which inhibited protein synthesis and resembled the ribosome-inactivating proteins from plants previously described. Thus, ribosome-inactivating proteins appear to be virtually ubiquitous in plants. PMID- 4031902 TI - Cell growth inhibitory glycosides from Asclepias amplexicaulis. PMID- 4031903 TI - Terpenoids from Viguiera potosina. PMID- 4031904 TI - Cucurbitacin B and isocucurbitacin B: cytotoxic components of Helicteres isora. PMID- 4031905 TI - Rehabilitation after severe brain injury: a follow-up study of a behaviour modification approach. AB - Twenty four patients with severe brain injury who had disturbed behaviours preventing rehabilitation or care in ordinary settings were treated in a token economy. This long-term follow-up study indicates that post-traumatic behaviour disorders can be lastingly improved, and that lengthy rehabilitation can have surprisingly good effects. PMID- 4031906 TI - Syringoperitoneal shunt for treatment of cord cavitation. AB - A series of twenty-nine patients with cord cavitation were treated by syringoperitoneal shunt. Twenty-two of them showed improvement after operation, five were unchanged and two worsened. Operation was performed in patients with post-traumatic cystic myelopathy, idiopathic syringomyelia, intramedullary tumours associated with cysts, and patients who had developed cystic myelopathy in association with spinal arachnoiditis. Pain improved in twenty patients, sensory symptoms and signs in eleven and weakness in ten. PMID- 4031907 TI - Pellagra encephalopathy among tuberculous patients: its relation to isoniazid therapy. AB - Eight cases of pellagra, diagnosed on the grounds of neuropathological findings and retrospective study of clinical data, were found among 106 necropsy cases of tuberculosis. Although these eight patients had shown various mental, neurological and gastrointestinal symptoms, as well as skin lesions, the diagnosis of pellagra had not been made clinically. In all the patients, pellagra symptoms appeared during isoniazid therapy. Death occurred 4 to 16 weeks later. Isoniazid inhibits the conversion of tryptophan to niacin and may induce pellagra, particularly in poorly nourished patients. Pellagra should be suspected whenever tuberculous patients under treatment with isoniazid develop mental, neurological or gastrointestinal symptoms, even in the absence of typical pellagra dermatitis. PMID- 4031908 TI - Absence of enhanced physiological tremor in patients without muscle or cutaneous afferents. AB - Patients with proprioceptive loss due to a neuropathy affecting large myelinated sensory nerve fibres were studied to determine the role of somaesthetic sensory inputs in enhanced physiological tremor. Involuntary movements in patients and controls attempting to hold the outstretched arm immobile were recorded during prolonged arm extension. Fatigue led to increased movements in both controls and patients but only the controls developed a rhythmic tremor. These data indicate that enhanced physiological tremor is dependent on somaesthetic afferent input. PMID- 4031909 TI - Hemidystonia: a report of 22 patients and a review of the literature. AB - Hemidystonia defined as involuntary, sustained posturing of the unilateral arm, leg, and face was studied in 12 male and 10 female patients. Hemidystonia was caused by cerebrovascular disease in eight patients, perinatal trauma or childhood injury in four, head trauma and its sequelae in three, neuronal storage disorders in two, neurodegenerative disease in two, lesions after thalamotomy in two, and presumed encephalitis in one. Sixteen patients (73%) had CT evidence of contralateral basal ganglia damage, history of hemiparesis, or both. Brain damage before 7 years of age produced contralateral hemidystonia with a mean delay of 9 7 years. In older patients hemidystonia appeared within 6 months after injury. Hemidystonia may result from a disconnection between the striatum and the thalamus with relative preservation of the corticospinal pathways. PMID- 4031910 TI - Pontine haemorrhage: a clinical analysis of 26 cases. AB - Correlation with the size of the haematoma, neurological findings and prognosis was studied in 26 cases of hypertensive pontine haemorrhage, using CT. A good prognosis was found with no or mild disturbance of consciousness, normal pupils, and transverse diameter of the haematoma 20 mm or less. Most of the patients with poor prognosis became comatose within two hours of onset. Their pupils were dilated bilaterally, pin-point or anisocoric and the transverse diameter of the haematoma was over 20 mm. PMID- 4031911 TI - The effects of hyperglycaemia on changes during reperfusion following focal cerebral ischaemia in the cat. AB - The effects of isosmolar loads of glucose and saline after onset of focal cerebral ischaemia (middle cerebral artery occlusion) were compared in cats. In cats given saline cerebral blood flow (CBF) fell and then rose slightly on the marginal gyrus (infarct penumbra). There was a sustained fall in CBF on the suprasylvian and ectosylvian gyri (infarct core). Reperfusion restored blood flow to preocclusion levels with no overall postischaemic hypoperfusion. Below ischaemic flows of 14 ml/100 g/min brain specific gravity was reduced in a smaller proportion of gyri by contrast with non reperfused cortex, suggesting that in some gyri resolution of cerebral oedema had taken place. GABA uptake was normal in the infarct core, but was reduced within the ischaemic penumbra. In animals given glucose after occlusion, CBF fell on the marginal gyrus during reperfusion. The degree of resolution of cerebral oedema was less than in saline infused cats. GABA uptake showed a pattern of abnormality similar to that seen in saline infused cats, except that uptake values were lower in the infarct core. Pial surface potassium activity remained elevated in the penumbra following reperfusion in glucose infused cats, but returned to normal in saline infused cats. Implications for the management of cerebral ischaemia in man are discussed. PMID- 4031912 TI - Chronic transformation of muscle in spasticity: a peripheral contribution to increased tone. AB - Mechanical properties of relaxed lower leg muscles were assessed by torque measurements during imposed constant velocity dorsiflexion-plantarflexion cycles. At low angular velocities, they exhibited an elastic and an energy-consuming, velocity-independent (plastic) resistance. In most patients with long-standing spasticity, both of these were enhanced. The results support the hypothesis of secondary structural changes of muscles in spasticity. PMID- 4031913 TI - Thermal discrimination thresholds in normal subjects and in patients with diabetic neuropathy. AB - Using two identical thermostimulators which operated on the Peltier principle, thermal cutaneous sensation of the hand and the foot was investigated in 36 normal subjects and in 20 patients with diabetic neuropathy. Using a two alternative forced-choice testing procedure, thermal discrimination thresholds were determined twice. The values found in normal subjects are comparable with data from the literature. It was confirmed that thermal discrimination of the foot decreased with increasing age. In patients with diabetic neuropathy the increased thresholds for the foot could be correlated with length-dependent degeneration of small nerve fibres. PMID- 4031914 TI - Cerebellar ataxia in enteric fever. AB - In a study of enteric fever, cerebellar ataxia was found to be the commonest neurological manifestation, second only to toxic delirium. Excluding toxic delirium (found in 25-30% of cases) neurologic deficit was noted in 5.0% of a series of 718 consecutive cases; 2.3% showed cerebellar ataxia, either as an isolated feature or in association with other lesions. The ataxia usually appeared in the second week, and lasted a mean of 9.4 days. In 90% of cases it had cleared completely within a month. PMID- 4031915 TI - The relationship of peripheral trauma and pain to dystonia. AB - Four patients are described who sustained comparatively minor peripheral injury, the affected area soon becoming the site of segmental dystonia. The movement disorder developed as the symptoms from the injury subsided, and except for the recent trauma, no cause for the dystonia was apparent; litigation was not an issue for any patient. It is suggested that on rare occasions peripheral trauma results in the development of dystonia. Since injury never involved the head, the role of the spinal dopaminergic system and the relevance of pain from the injury are discussed in considering possible underlying mechanisms. PMID- 4031916 TI - Reaction time of patients with Parkinson's disease, with reference to asymmetry of neurological signs. AB - Electromyographic reaction times of the left and the right finger extensor muscles in extension movement of the wrist were examined in 42 patients with Parkinson's disease, and 20 normal subjects. Compared to the normal subjects and the patients with neurological signs confined to the right side, the patients with neurological signs on the left side or on both sides showed slowing of reaction times regardless of the side of responding hand. The patients with asymmetry of bilateral neurological signs showed slower RTs on the more affected side. PMID- 4031917 TI - The value of the measurement of cerebrospinal fluid levels of lysozyme in the diagnosis of neurological disease. AB - A turbidimetric technique has been adapted to yield maximum sensitivity for the measurement of lysozyme in cerebrospinal fluid. One hundred and ninety-eight patients were studied over a total period of 9 months using this technique. In addition to the considerably elevated levels known to occur in cases of bacterial and fungal meningitis, increased activity was also demonstrated in cases of subarachnoid haemorrhage and in certain inflammatory conditions. Normal or marginally increased levels were seen in cases of viral meningitis and encephalitis. PMID- 4031918 TI - Neuropsychological functions in the follow-up of transient global amnesia. PMID- 4031919 TI - Acute acquired toxoplasmosis causing neuroptico-meningoencephalitis in an immunocompetent boy. PMID- 4031920 TI - "True" cystic meningioma. PMID- 4031921 TI - Stroke due to atrial myxoma in a young woman with co-existing acoustic neuroma and pituitary adenoma. PMID- 4031922 TI - Multiple adverse reactions following metrizamide myelography. PMID- 4031923 TI - Paraspinal myoclonus due to spinal root lesion. PMID- 4031924 TI - Failure to promote spinal cord regeneration in rats with immunosuppressive treatment. PMID- 4031925 TI - Reflex path length and clonus frequency. PMID- 4031927 TI - Myasthenia gravis: long-term prognostic value of thymus lactate dehydrogenase isoenzyme pattern of hyperplastic thymus and thymoma. AB - Lactate dehydrogenase (LDH) isoenzyme pattern and the percent of H-subunit content were determined in the thymus of 62 patients (55 with hyperplasia, 7 with tumours) after thymectomy. An increase in LDH1 relative activity indicates that in the thymus of patients with myasthenia gravis the ratio of mature differentiated thymocytes was higher than in the thymus of control subjects. LDH isoenzyme profiles of thymus tumours were similar to those described in other neoplasms, except that thymomas with apparent predominance of epithelial cells and with minimal lymphocytic reaction exhibited a marked elevation only in LDH2 relative activity, presumably associated with the specific (secretory) function of epithelial cells. The elevation of H-subunit content, a parameter characteristic of both thymic components (lymphoid and epithelial), correlated closely with a poor clinical condition in patients several years after surgery. PMID- 4031926 TI - Combined scatter diagrams of sheath thickness and fibre calibre in human sural nerves: changes with age and neuropathy. AB - A computer-assisted method permits collection of large numbers of measurements of fibre profiles in electron micrographs of human sural nerve biopsies. The method is based on simultaneous demonstration of fibre calibre and of sheath thickness in terms of the g-ratio (quotient axon diameter/fibre diameter), and on the recalculation of all parameters for circular fibre profiles. The fibres of small and large diameters of human sural nerves were found to form separate populations with distinctly different trends for sheath thickness and also different patterns of maturation. Preliminary data in neuropathy show that this method gives a better distinction of the extent of damage to either of the two populations; it also permits assessment of the number of regenerating or remyelinating fibres. PMID- 4031928 TI - Bladder dysfunction in distal autonomic neuropathy of acute onset. AB - A patient with cholinergic dysautonomia and a patient with pandysautonomia have each been investigated for disturbances of bladder and urethral function. Both patients suffered from an inability to develop or sustain a detrusor contraction, while retaining normal bladder sensation. Biopsy specimens of bladder muscle stained for acetylcholinesterase revealed a significant reduction in cholinergic nerves compared with controls; however, the prominent cholinergic subepithelial plexus was strikingly preserved. These findings lend support to the view that acetylcholinesterase-containing nerves in the bladder muscle are motor fibres responsible for detrusor contraction, while those located in the subepithelium are sensory in function. Urethral sphincter electromyography revealed no abnormality of individual motor units, confirming that motor unit integrity in this muscle is dependent upon somatic rather than autonomic innervation. In the patient with pandysautonomia the proximal urethra was incompetent, while in the patient with cholinergic dysautonomia the bladder neck remained closed, as in controls. This suggests that sympathetic rather than parasympathetic efferent activity is necessary for the maintenance of proximal urethral competence. PMID- 4031929 TI - Effects of chronic low frequency electrical stimulation on normal human tibialis anterior muscle. AB - The loss of force that occurred during intermittent electrically evoked tetanic contractions was determined for the tibialis anterior muscle of normal subjects. Adult muscles showed a characteristic reduction of tension over the first two to three minutes until a steady plateau was reached. Muscles of young children showed no comparable decrease of the initial tension in response to this method of fatigue testing. After fatigue the muscles of both groups of subjects produced a higher proportion of tension at lower rates of stimulation. Following prolonged chronic low frequency stimulation at 8-10 Hz, adult muscles showed a significant increase (p less than 0.01) in fatigue resistance compared to unstimulated control: the muscles of the normal child showed no measured change. It is concluded that it is possible to alter the properties of adult human muscle by superimposed low frequency electrical stimulation. PMID- 4031930 TI - Increased co-activation of the upper limb muscles in writer's cramp. AB - Eleven patients with writer's cramp were studied during the performance of a series of writing and non-writing tasks. Their performance in the tasks and the intensity of contraction in the flexor and extensor muscles of the fingers and elbow (recorded electromyographically) were compared with the results from a group of matched normal controls. The patients showed highly significant increases in muscle activation especially in the triceps muscle which was overactive in all but one of the tasks undertaken. Psychometric testing showed no difference between patients and controls. The results support the view that writer's cramp is a form of focal dystonia in which the disorder of motor control is not confined to writing activities. PMID- 4031931 TI - The variation of finger tremor with age in man. AB - The variation of the amplitude and frequency of finger tremor was studied in 190 subjects ranging in age from 7 to 77 years. Tremor was measured in various postures with an accelerometer and a transduced signal was analysed by Fourier analysis. The variation of tremor frequency and amplitude with age depended upon the posture adopted for measurement and in certain postures some of the variation was related to changes in stature with age. PMID- 4031933 TI - Cerebellar calcification and lead. AB - In elderly subjects who were brought up in a known high lead environment in Queensland, Australia, childhood residence and occupational status provide circumstantial evidence of a relationship between excessive lead intake and cerebellar calcification as seen on computed tomography. This supports experimental and neuropathological studies demonstrating an association between exposure to lead and perivascular cerebellar calcification. PMID- 4031932 TI - Neurological and neuropsychological effects of cerebral spinal fluid shunting in children with assumed arrested ("normal pressure") hydrocephalus. AB - Normocephalic children found to have ventriculomegaly during evaluation of long standing (4.5-8.5 years) neurological disorder were tested for academic achievement, intellectual quotient and neuropsychological functioning. Radioactive iodinated serum cisternography, pre and post-shunt electrophysiological studies (visual evoked responses, brainstem auditory evoked potentials, sleep electroencephalograms) and radiological studies (skull radiographs computed tomography) were recorded. Four children who have been followed more than one year after insertion of ventricular-peritoneal shunts are presented. All demonstrated improvement in psychometric findings along with some improvement in CT scan and EEG studies. The most marked initial changes were noted on measures of neuropsychological performance, accompanied later by improvement in measures of intelligence. Achievement test scores showed no consistent pattern of change. This sample suggests that there is a group of asymptomatic children with apparent clinically stable (arrested) hydrocephalus in whom abnormal neuropsychological testing indicates the need for cerebrospinal fluid shunting, with subsequent improvement. PMID- 4031934 TI - Usefulness of intraoperative cortical blood flow measurement by heat clearance method for monitoring cerebral ischaemia during therapeutic carotid ligation. AB - Changes of regional cortical blood flow (rCBF) was monitored by the heat clearance method during the operation of cervical carotid ligation combined with superficial temporal artery and middle cerebral artery anastomosis for the treatment of inaccessible aneurysms of the internal carotid artery in eight patients. There were three types of rCBF responses upon closure of the internal carotid artery, with or without bypass blood flow. Based on the responses, the internal carotid artery was ligated abruptly or occluded gradually. The usefulness of the method for monitoring cerebral ischaemia for therapeutic carotid ligation is discussed. PMID- 4031935 TI - Simulated paraplegia: an occasional problem for the neurosurgeon. AB - Fourteen cases of simulated paraplegia and tetraplegia encountered amongst 4,800 neurosurgical admissions are described. The classification of such cases is difficult. Use of the term "hysteria" depends on whether the behaviour is judged to be conscious or not, but this can rarely be decided. In most of the patients the paralysis was of relatively short duration and recovered rapidly with simple methods of treatment which permitted this to occur without loss of face, but such cases presenting as acute neurological emergencies represent only one relatively simple form of pretended or "hysterical" illness. Many of these patients are probably never seen by psychiatrists. PMID- 4031936 TI - Pain in motor neuron disease. AB - Twenty-seven of 42 patients with motor neuron disease had significant pain. The nature and duration of the pain are described along with an illustrative case report. The aetiology and most effective treatment of this common complication of motor neuron disease remain unclear. PMID- 4031937 TI - CT brain scan in acute water intoxication. PMID- 4031938 TI - Cortical vasoactive intestinal peptide in relation to dementia in Parkinson's disease. PMID- 4031939 TI - Acute myelopathy in a drug abuser following an attempted neck vein injection. PMID- 4031940 TI - Solitary neurofibroma of the lumbosacral plexus. PMID- 4031941 TI - Behavioral manifestations of third ventricular colloid cysts. PMID- 4031942 TI - Neuropsychological evaluation of mild head injury. PMID- 4031943 TI - Ambulatory EEG monitoring. PMID- 4031944 TI - Olfaction in dementia. PMID- 4031945 TI - Millipore diffusion chambers allow dissociation of myelin phagocytosis by non resident cells and of allogenic nerve graft rejection. AB - Allogenic graft rejection leads to rapid tissue destruction of nerves transplanted directly into a muscle lodge. If the nerves are enclosed in 5.0 micron pore chambers and transplanted into the peritoneal cavity, there is no allogenic graft rejection. The phagocytosis of myelin by invading cells is, however, not disturbed, showing that these cells can distinguish the degenerating myelin from the Schwann cell without being responsive to the Schwann cell's allotype. If the allografts are allowed to predegenerate for 4 wk in 0.22 micron pore chambers which do not admit any cells, there is a striking mitigation of the allogenic graft rejection if the nerves are subsequently released from the chamber. Myelin phagocytosis in such nerves is also reduced. These observations indicate the existence of a hierarchy of cellular recognition mechanisms involved in nerve tissue degradation. Phagocytosis of the myelin sheath by macrophages involves recognition mechanisms which differ from those of the allogenic rejection of the Schwann cell, presumably mediated by T lymphocytes. PMID- 4031946 TI - Fine structure of astrocytic processes during serum-induced demyelination in vitro. AB - Astrocytic changes were examined ultrastructurally during serum-induced demyelination in organotypic cultures of mouse spinal cord tissue. The myelin sheaths of most myelinated fibers showed myelin breakdown. Sheet-like astrocytic processes completely and closely surrounded the demyelinating fibers and frequently engulfed myelin fragments. These processes were virtually devoid of glial filaments or microtubules and contained flocculogranular material, round and elongated cisterns and glycogen granules. Penetration of the myelin sheath by astrocytic processes was only rarely found. The cell body of the astrocyte was never insinuated between the myelin sheath and the axon. No endocytosis of myelin droplets via coated pits on the surface of astrocytes was observed. In comparison with phagocytic mononuclear cells in vivo, astrocytes in vitro dispose of myelin debris less actively. Astrocytes in serum-induced demyelination probably play a nonspecific but fundamental role during degeneration in segregating damaged nerve fibers from surrounding neuronal elements. PMID- 4031947 TI - Inflammatory vasculitis in multiple sclerosis. AB - Fifty-two plaque or lesion areas were examined from 25 cases of multiple sclerosis. Twenty-four of these showed acute features, whereas the rest were more chronic in nature. The acute lesions showed lymphocytic infiltration (79%), fibrinous exudation (63%), lymphocytic meningitis (50%) and venulitis (58%). Of the chronic lesions, there were only 21% with lymphocytic infiltration, 11% with fibrinous exudates, none with meningitis, 29% with organising endovenulitis, 36% with fibrosed vein walls. The finding of a fibrinous inflammatory exudate in the acute lesion is a new observation in multiple sclerosis. Likewise, the observation of an inflammatory infiltrate confined to the vein wall (and often present at a distance from the plaque) has not been previously recorded in the disease. The chronic lesion, by contrast, showed relatively little fibrin, but there was considerable reparative thickening of the walls of the involved veins. The evidence provides new humoral and cellular evidence of an inflammatory process in multiple sclerosis which precedes or is not directly associated with the demyelinating process. PMID- 4031948 TI - Anti-acetylcholine receptor antibodies in myasthenia gravis. Part 3. The effect of thymectomy. AB - The clinical condition and the serum levels of antibodies to acetylcholine receptor protein were followed in 30 patients with myasthenia gravis before and in a period varying from 2 to 4 (mean 3) yr after thymectomy. Twenty-five patients improved in the 2 yr following thymectomy. A highly significant correlation was found between the change in clinical condition and the change in antibody levels. Only 3 patients improved without a fall of antibody level. Prethymectomy antibody levels were positively correlated with the severity of the clinical condition and with the degree of thymus hypertrophy. PMID- 4031949 TI - Agyria (lissencephaly) with anomalous pyramidal crossing. Case report and review of literature. AB - A case of agyria (lissencephaly) with a highly unusual course of the corticospinal tract at the crossing and in the spinal cord is described. Published cases of agyria (lissencephaly) are reviewed with special attention to the cortical fiber system and organization of the necortex, and their implications for possible pathogenetic mechanisms. The problem of nomenclature is discussed. PMID- 4031950 TI - Monoclonal antibodies and the biological approach to cancer. PMID- 4031951 TI - Activation of tumoricidal properties in macrophages and inhibition of experimentally-induced murine metastases by a new synthetic acyltripeptide, FK 565. AB - The effect of FK-565, a novel low molecular weight (MW) acyltripeptide, on tumoricidal properties of murine macrophages is reported here. Peritoneal macrophages (PMs) harvested from C57BL/6 mice and beige mice were rendered cytotoxic to syngeneic B16 melanoma cells following their interaction in vitro with FK-565. Maximal and reproducible activation of tumoricidal properties in PM were obtained by interaction in vitro with 25 micrograms/ml of FK-565 for a 24 h period, and as little as 0.5 microgram/ml of FK-565 was sufficient to induce significant cytotoxicity. Murine PMs activated by FK-565 in vitro were cytotoxic to syngeneic and xenogeneic tumor cells, but did not affect allogeneic nontumor cells. The PMs were also activated to kill B16 melanoma cells by intraperitoneal injections of FK-565 (10 mg/kg). Multiple injections of FK-565 into mice also slightly but significantly inhibited lung metastases. These results suggest that FK-565 has potential as an effective immunopotentiator in immunotherapy. PMID- 4031952 TI - Evaluation of effects of levamisole and surgery on canine mammary cancer. AB - Three hundred and forty-five dogs with mammary tumors were initially evaluated for study. One hundred and forty-four dogs with untreated malignant mammary tumors (136 adenocarcinomas, 5 malignant mixed, 3 sarcomas) were selected for study. All dogs were clinically staged and stratified on the basis of tumor volume and body weight. Dogs were randomized to either a radical mastectomy or simple mastectomy group, and then further randomized to a levamisole or placebo group. There was no significant difference in either survival time or cancer-free survival time between the surgery groups or between the levamisole and placebo groups. The most significant prognostic factor was tumor volume; dogs with tumors less than 41 cc had significantly enhanced survival time (p = 0.0007) and cancer free survival time (p = 0.0005). PMID- 4031953 TI - Cockayne syndrome: clinicopathologic and tissue culture studies of affected siblings. AB - Two siblings with Cockayne syndrome (CS) had extremely severe and early onset cachectic dwarfism, developmental delay, cataracts, microcephaly, peripheral neuropathy, and spastic quadriplegia. In order to study the inherited DNA-repair defect known to be present in cultured CS cells, a lymphoblastoid line was established from the younger sibling. Tissue culture studies revealed the line to have a hypersensitivity to the lethal effects of 254-nm ultraviolet radiation (UV) equivalent to that of lymphoblastoid lines from CS patients who had either the usual severity or a very mild form of CS. Autopsy of the older sibling at six years of age showed the brain to be severely atrophic, with particularly severe cerebellar atrophy. There was a marked reduction in the number of granule cells in the cerebellum and irregular patchy myelination throughout the brain. Many astrocytes contained either a large, bizarre-shaped nucleus or multiple nuclei. Some Purkinje cells of the cerebellum and pyramidal neurons of the hippocampus were binucleated. It is suggested that the DNA-repair defect of CS causes abnormalities in nuclear DNA replication and cell division which result in cell death and in the observed nuclear abnormalities. PMID- 4031954 TI - Remarks on the follow-up of cerebellar astrocytomas. AB - A retrograde study was performed in 105 patients operated upon between 1950 and 1972 for a cerebellar astrocytoma. Complete histories were available for 89 patients. Forty-five patients died within the first 3 months after operation. Of the 32 patients who were still alive, 14 patients had been operated upon 20-30 years previously and 18 patients 10-19 years previously. Twelve patients died over 3 months after the operation; in 6 cases, recurrence of tumour was the cause of death. Of the 7 patients who were irradiated post-operatively, 5 died. In 26 patients the tumor had infiltrated the brain-stem and only 7 patients survived the operation. However, 2 patients are still alive after 25 and 10 years, respectively. The findings indicate that patients operated upon for a localized cerebellar astrocytoms can be considered cured and irradiation and chemotherapy are not warranted. When the tumour has infiltrated the brain-stem, a survival period of more than 20 years is possible after partial resection. PMID- 4031955 TI - The causes of stroke in the young. AB - In a group of 75 patients under the age of 45 years with stroke, ischaemic cerebral infarction was diagnosed in 60 patients and primary intracerebral haemorrhage in 15. Trauma was found to be the commonest identifiable predisposing factor to cerebral infarction, being present in 13 cases (22%). Migraine was the second most commonly identified predisposing factor while atheroma and hypertension were infrequent. Such a high frequency of preceding trauma has not previously been described, perhaps because it is not generally appreciated that the delay between the traumatic event and subsequent stroke may be considerable. The diagnostic management of young stroke patients is considered with particular reference to the indications for specialized cardiac and neuroradiological investigations. PMID- 4031957 TI - Chronic neurogenic quadriceps amyotrophies. AB - Two cases of quadriceps amyotrophy, probably of chronic neurogenic origin are reported. Only the knee jerks were diminished, the calves hypertrophic, and the serum creatine kinase level very high in one case, and there were neurogenic electromyographic abnormalities in the quadriceps. In the first case, biopsy of the quadriceps muscle revealed a neurogenic origin with hyalinized hypertrophic fibres. CT scan showed abnormalities not only in the quadriceps but also in the sartorius, gracilis and gastrocnemius muscles. A second biopsy specimen from the gastrocnemius muscle showed histological findings similar to those of the quadriceps. In the second case, the EMG and biopsy findings suggested a myogenic origin, but 6 years later they were compatible with neurogenic atrophy. Differentiation from Becker dystrophy is very difficult in the first case and the second case is more a focal spinal amyotrophy. Further, in spite of their localization, the extension of the affected muscles changes the diagnosis. The same applies to chronic quadriceps amyotrophy in general, which cannot be regarded as an entity, but which suggests muscular dystrophy, spinal atrophy, polymyositis or a metabolic disorder. These cases can be compared with the four cases reported in the literature, which were regarded as a "forme fruste" of chronic spinal amyotrophy. PMID- 4031956 TI - Ischaemic oculomotor nerve palsy. Clinical features and vascular risk factors in 23 patients. AB - Of 61 patients with isolated third nerve palsy, 23 (38%) had the characteristic clinical features of an ischaemic oculomotor nerve palsy. The essential sign of this usually painful disorder of acute onset was a marked discrepancy between complete or severe paresis of the extraocular muscles innervated by the third nerve, and sparing of the pupillary sphincter. All patients had completely recovered within 3 months. Fourteen had a history or on follow-up had other cranial mononeuropathies. Except for two patients, all were above the age of 60 years. Of the 23 cases, 11 had diabetes mellitus and 8 an abnormal glucose tolerance test, while in 4 the latter was normal. Almost all had hypertension and were overweight, and half were smokers. In 18 patients, four or five vascular risk factors were present. PMID- 4031958 TI - Acid phosphatase activity of cerebrospinal fluid cells in leptomeningeal haemorrhage. AB - One hundred and twenty samples of haemorrhagic spinal fluid were examined by acid phosphatase staining. This enzyme activity starts to appear in mono-histiocytic cells 2 days after bleeding and increases up to the 5th day. After 1 week the activity decreases rapidly. Similar results are found in mixtures of incubated clear spinal fluid, to which blood is added. Acid phosphatase staining is a useful additional method for determination of the age of a leptomeningeal bleed. PMID- 4031959 TI - Apurulent bacterial meningitis (compartmental leucopenia in purulent meningitis). AB - Meningococci and Haemophilus influenzae may invade the subarachnoid space during the bacteriaemic phase without impairment of the blood-CSF barrier and in the absence of any leucocyte reaction. In pneumococcal meningitis the CSF may also contain less than 100 cells/microliter despite the presence of "pure bacterial cultures", but the barrier is completely broken when the serum/CSF concentration ratio is below 10. A clinical analysis of eight patients with fewer than 100 cells/microliter revealed that the first symptoms of meningitis appeared at least 3 days prior to the diagnostic lumbar puncture. There was a strong neutrophilic reaction in the blood with a prevalence of juvenile forms in most cases, indicating intact antibacterial defence mechanisms. Within 24 h after the start of antibiotic therapy the cell number rose above 2000/microliter accompanied by disappearance of pneumococci. Six of the eight patients died. In three cases autopsy revealed thick layers of pus over the convexities, indicating a compartmental separation of the ventricles and the spinal subarachnoid space. In one case of late diagnosed bacterial meningitis with a pleocytosis of 430/microliter the CSF lysozyme level was seven times higher than compatible with this cell number. Hyperphagocytosis and cellular disintegration is thought to cause the leucopenia within the spinal CSF compartment. "Apurulent bacterial meningitis" can be seen as a disease entity that is a diagnostic pitfall and also a prognostic sign. PMID- 4031960 TI - Chorea and polycythaemia. AB - Two patients with chorea and polycythaemia vera are described. The literature on this rare association is reviewed and its pathophysiology discussed. PMID- 4031961 TI - Visual evoked potentials in ataxia telangiectasia. AB - Pattern reversal visual evoked potentials (VEPs) elicited in four patients with ataxia telangiectasia revealed normal results in two and absent responses in two. The pathogenesis of the VEP abnormalities is discussed. It is surmised that the VEP changes reflect progressive degeneration of the nerve fibres in the anterior visual pathway, as in Friedreich's ataxia. PMID- 4031962 TI - High single-dose alternate-day corticosteroid regimens in treatment of polymyositis. AB - High single-dose alternate-day prednisolone therapy (ADT) was compared with daily dose prednisolone therapy (DDT) for treatment of polymyositis. Thirty patients with polymyositis were treated with ADT for an average of 33.9 months. The combined number of improvements was 21 out of 30, a response rate of 70%. Side effects were very rare and mild. On the other hand, 9 of 17 patients treated with DDT for an average 18.5 months improved, a response rate of 53%. The incidence of side-effects was strikingly higher than with ADT. ADT is therefore strongly advocated for treatment of polymyositis to avoid infectious complications and lessen cushingoid side-effects. PMID- 4031963 TI - Improvement of atactic syndrome after longer periods of alcohol abstinence. PMID- 4031964 TI - Unilateral true hypertrophy of the calf muscle. PMID- 4031965 TI - Abstracts. IIIrd International Brain Heart Conference. A satellite symposium of the XIIIth World Congress of Neurology. Trier, Federal Republic of Germany, September 7-9, 1985. PMID- 4031966 TI - Randomized trials in rare tumors. PMID- 4031967 TI - A systemic lymphoproliferative disorder with morphologic features of Castleman's disease: clinical findings and clinicopathologic correlations in 15 patients. AB - Fifteen patients (11 males, four females; median age 57) manifested a disease characterized by (1) the histopathologic features of Castleman's disease, plasma cell type, in lymph node biopsies; (2) predominantly lymphadenopathic disease, involving multiple, preferentially peripheral nodal groups; (3) varied manifestations of multisystemic involvement (such as constitutional symptoms; splenomegaly and hypergammaglobulinemia; elevated ESR, anemia, and thrombocytopenia; hepatomegaly and altered liver function tests (LFTs); signs of renal disease); and (4) idiopathic nature. Two main patterns of evolution were recognized: persistent, with sustained clinical manifestations, and episodic, with recurrent exacerbations and remissions. Seventy-three percent of patients had infectious complications, and 27% developed malignancies. Complete remissions were obtained occasionally with antineoplastic agents and with splenectomy but not with glucocorticosteroids alone. The median survival time is 30 months; 60% of patients have died. Median follow-up in the six surviving patients is 97+ months. A review of 50 cases in the literature revealed similar clinical and laboratory features. Despite some similarities with autoimmune diseases, the main features of this process seem to best fit a hyperplastic-dysplastic lymphoid disorder in a setting of immunoregulatory deficit. PMID- 4031968 TI - Blood glucose levels in Hodgkin's disease. PMID- 4031969 TI - Histologic and non-histologic factors correlated with survival time in supratentorial astrocytic tumors. AB - One hundred and ninety-two cases of supratentorial astrocytic tumors are classified in 4 groups according to the presence or absence in the pathological material of simple morphological criteria: abnormal cellular density, nuclear pleomorphism, neovascularization, necrosis. Each one of these criteria is strongly correlated with prognosis. Nevertheless only a simple classification in low and high grade lesions has a definite predictive value. A multivariate analysis utilizing Cox's hazard function confronts these histological findings with a number of clinical and etiological possible factors of prognosis. Age and performance status at the time of diagnosis are the best predictors of survival time. The clinical use of a predictive model derived from Cox's function analysis is discussed. PMID- 4031970 TI - Central nervous system pharmacokinetics of high-dose cytosine arabinoside. AB - The cerebrospinal fluid (CSF) pharmacokinetics of cytosine arabinoside (Ara-C) was determined in 8 patients with metastatic cancer in the central nervous system. High dose (3 gm/M2) one-hour intravenous infusions of Ara-C were given with serial CSF sampling obtained from indwelling Ommaya reservoirs. CSF was analyzed by high pressure liquid chromatography. Mean Ara-C elimination half life of 140 minutes in CSF was eight times longer than that in plasma. The peak mean CSF concentration of Ara-C (2.1 micrograms /ml) was about 7% of the plasma concentration (30 micrograms/ml). A total of 28 treatment courses were administered with minimal hematopoietic, gastrointestinal and neurological toxicities. A schedule of administration of 2 high-dose treatments 12 hours apart repeated every two weeks should maintain cytotoxic CSF concentrations which could prove useful in the management of CNS leukemia and lymphoma. PMID- 4031971 TI - Interferon-beta in patients with low-grade astrocytomas--a phase I study. AB - In 3 patients with low-grade astrocytomas clinical pharmacology of interferon beta (10(7) U/mg protein) was investigated. Interferon-beta with escalating dosage (2.3, 6.9, 23, 69 X 10(6) U/patient) was given to each patient in 4 infusions at weekly time intervals. In these patients dose-dependent plasma levels of interferon-beta of up to 5800 IU/ml were achieved. Plasma concentrations showed a biphasic decline (T1 1/2:0.095-0.49 hrs and T2 1/2: 5 14.5 hrs). Side effects were: mild fatigue, myalgia, tachycardia, hypertension, and fever; the latter was well controlled by pretreatment application of paracetamol. Hematological changes included lymphopenia (2-6 hrs after infusion) and granulocytosis (3-6 hrs after infusion). Natural Killer cell activity was also monitored: 6 hours after infusion a drop of activity - not clearly dose dependent - was observed to a minimum of 1% pretreatment activity; 24 hrs after infusion activity increased up to a maximum of 400%. In this phase I study high biological activity of interferon-beta could be detected in plasma of astrocytoma patients - clinical tolerance was good and only mild toxicity was observed. PMID- 4031973 TI - Apparent glucose utilization in Walker 256 metastatic brain tumors. AB - Regional rates of apparent glucose utilization (GU) in metastatic Walker 256 (WL 256) brain tumors produced by the intracarotid injection of WL-256 tumor cells in rats were measured using 14C-deoxyglucose and quantitative autoradiography. Apparent glucose utilization was uniform within individual small and medium size tumors without necrosis, varied considerably among different tumors within this group, and did not correlate with tumor size or location. High values of GU in medium and large-size tumors correlated with viable-appearing tissue in contrast to necrotic tissue and were always 1.3 to 3 times higher than that of adjacent and contralateral nontumorous brain. The apparent net extraction of glucose (En*) in viable tumor regions was estimated to be several fold higher than that in remote brain tissue; analysis of this data for medium and large tumors indicates that the calculated values of GU and En* overestimate the actual rates of utilization and net extraction of glucose. Local cerebral glucose utilization (LCGU) was higher than normal adjacent to small tumors and lower than normal adjacent to larger tumors. The LCGU in many gray-matter structures remote from the intracerebral tumors was reduced and roughly proportional to the metastatic tumor burden. The comparatively high uptake of 2-deoxyglucose by viable tumor cells has diagnostic value and suggests that appropriate glucose analogues could be developed to produce a tumor-selective inhibition of glycolysis and tumoricidal effect. PMID- 4031974 TI - The role of monoclonal antibodies in brain tumour diagnosis and cerebrospinal fluid (CSF) cytology. AB - This paper reviews the diagnostic role of monoclonal antibody immunohistochemistry in a series of 189 brain tumour biopsies and 22 cases of neoplastic meningitis. The diagnostic monoclonal antibody panel, which includes markers for glial, neural, epithelial and lymphoid differentiation antigens, was used to test a wide variety of cerebral and spinal tumours by indirect immunofluorescence and immunoperoxidase techniques on unfixed frozen sections. Gliomas, meningiomas, schwannomas, medulloblastomas, choroid plexus tumours, cerebral lymphomas and metastatic carcinomas could all be reliably differentiated by means of their characteristic antigenics profiles, as defined by their patterns of reactivity with the antibody panel. Confident diagnosis was possible even in very poorly differentiated tumours and in biopsies distorted by surgical squeeze artefact, where paucity of morphological clues made diagnosis by conventional histological methods difficult or impossible. It was estimated that use of the antibody panel was responsible for, or made a significant contribution towards the final diagnosis in approximately 20% of cases. The monoclonal reagents were also found to be of great value in the detection and characterisation of neoplastic cells in CSF specimens from patients with malignant meningitis. Malignant cells were detected in 73% of cases and characterised in 16% of cases by routine cytological techniques. Employing monoclonal immunocytology however, these figures were improved to 95% and 95% respectively. Our findings suggest that patients with neoplastic meningitis can be spared prolonged investigation and inappropriate management by the early detection and characterisation of malignant cells in CSF using panels of monoclonal antibodies. PMID- 4031972 TI - Differentiation markers (S-100, GFAP, NSE and D2) in fetal rat brain cells during malignant transformation in cell culture. AB - Malignant cell lines obtained by ethylnitrosourea (EtNU)-induced transformation of fetal rat brain cells in culture express protein markers of different types of neural cells. These are the nervous system-characteristic S-100 protein; glial fibrillary acidic protein (GFAP); neuron-specific-enolase (NSE), and the D2-cell adhesion molecule. S-100 protein was absent in fetal brain cells in culture, but gradually appeared in the later stages of malignant transformation and further increased at onset of rapid growth of atypical cells (stage IV). GFAP and D2 were weakly expressed in primary fetal brain cells and did not change throughout malignant transformation. NSE was present in both normal and carcinogen-treated fetal brain cells, and increased at later stages of malignant transformation. From stage III (40-100 days) some cultures were strongly positive and some negative, and the same was seen in the resulting tumorigenic cells about 100 days later. In conclusion the stepwise process of malignant transformation of brain cells in culture ended with a stable phenotype of cells capable of expressing varying types of differentiation markers. The presence of these markers in rat brain cells undergoing malignant transformation may indicate that EtNU given at 18th days of gestation is acting on multipotent neuroectodermal cells. PMID- 4031975 TI - Immunolocalization of monoclonal antibody-defined extracellular matrix antigens in human brain tumors. AB - The extracellular matrix is involved in many aspects of tumor cell biology, including tumor invasion and metastasis. 2A6 and 81C6 are murine monoclonal antibodies that identify glioma-mesenchymal extracellular matrix antigens. The 81C6 antigen is a high molecular weight glycoprotein composed of Mr 230,000 subunits. The expression of 2A6 antigen, 81C6 glycoprotein, fibronectin (FN), and laminin (LN) was examined immunohistochemically in ten malignant gliomas (MG) and four medulloblastomas (MBT). 2A6 and 81C6 were expressed in similar patterns by the neoplastic neuroepithelial cells in 9/10 MG and 1/4 MBT. The staining was typically diffuse and amorphous, without visualization of distinct cell bodies or processes. Less frequently, antigen was detected within tumor cell cytoplasm. In most tumors the staining was greatest in the perivascular regions. In two MG, 2A6 and 81C6 were expressed only by a subpopulation of neoplastic cells. Although intense staining was also associated with hyperplastic vascular and mesenchymal cells, many small and medium size blood vessels stained weakly or not at all. In contrast, FN and LN were expressed uniformly and intensely in the tumor vasculature, but were not expressed by neoplastic neuroepithelial cells. The 2A6 antigen and 81C6 glycoprotein are immunohistochemically distinct from FN and LN. These monoclonal antibody-defined antigens are heterogeneously expressed by neoplastic neuroepithelial cells and hyperplastic vascular-mesenchymal elements in MG and MBT. The 2A6 and 81C6 monoclonal antibodies will be useful reagents in the investigation of the extracellular matrix of malignant neuroepithelial neoplasms. PMID- 4031976 TI - Delayed adverse effects after irradiation of gliomas: clinicopathological analysis. AB - Out of 107 pts. treated with radio- and chemotherapy for low and high grade gliomas (TD: 45-65Gy), 3 cases developed pathologically documented radionecrosis (coagulative necrosis with minimal or no persistent tumor). Clinico-therapeutic modalities were analyzed for all cases and biologically equivalent doses were calculated according to NSD, ED and btu formulas. All cases of radionecrosis fell into the group of doses close to 60Gy/30fx./42d. and NSD = 1758, ED = 1340 and btu = 1161. Isodose curve reconstruction on planes corresponding to histological sections of brains with radionecrosis demonstrated that doses received by areas of necrosis were higher than the calculated mid-plane doses in two cases. Clinical and autoptic incidence of radionecrosis were 2.8% and 10% respectively. High doses of steroids during RT seemed to offer some protection against radionecrosis, while number of chemotherapy cycles did not influence the risk of radionecrosis. A higher autoptic rate of irradiated gliomas is needed in order to obtain a better understanding of a number of unresolved problems. PMID- 4031977 TI - Survival and prognosis of patients with astrocytoma with atypical or anaplastic features. AB - This study confirms the importance of histologic tumor necrosis as a major prognostic variable in malignant glioma. Necrosis is present in glioblastoma multiforme (GBM), and absent in astrocytoma with atypical or anaplastic features (AAF). This paper evaluates 94 patients with AAF and 462 patients with GBM treated with radiation therapy with or without BCNU on 3 consecutive randomized protocols of the Radiation Therapy Oncology Group (RTOG) between 1974 and 1983. Multivariate analyses of the 556 patients confirmed histology as a significant independent variable that is prognostically relatively more important than Karnofsky performance status (KPS) and extent of surgery, and somewhat less important than age. The median survival for AAF was 36.2 months and for GBM was 8.6 months. In addition, separate multivariate analyses of AAf cases determined that the extent of surgery is a significant independent variable that is relatively more important than KPS, but less important than age. The median survival of AAF patients who underwent surgical excision was 46.8 months compared with 15.2 months for those biopsied (p less than .001). PMID- 4031978 TI - Human eye movements associated with blinks and prolonged eyelid closure. AB - Eye movements associated with eyelid closure were recorded in human subjects with search coils, embedded in self-adhering scleral annuli, in a magnetic field. In contrast to classical notions, voluntary as well as reflex blinks were consistently accompanied by transient downward and nasalward movements of both eyes with amplitudes 1-5 degrees. These eye movements had a shorter duration than the upper lid movements, and the shapes of the spatial trajectories of eye and lid movements were not similar. The trajectory of the eye movements was only modestly affected by gaze eccentricities up to 15 degrees; there was a tendency for the downward component to be enhanced by looking upward, and vice versa. Restraining of the lids of one eye in the open or closed position did not significantly alter the eye movements during (attempted) blinks. Velocity amplitude-duration relations of the down- and upward components were similar for the same eye before and after closure and for the closed eye and the contralateral unrestrained eye. The velocity-amplitude-duration characteristics of saccades were also unaffected by prolonged closure of the lids of one eye. Prolonged, voluntary closure of the lids was followed by a slow, tonic ocular deviation, which was consistently upward in half of the subjects and consistently downward in the other half. Additional horizontal components were highly variable even within subjects. In one subject the downward deviation was converted into upward deviation when lid closure was mechanically impeded. We conclude that elevation of the eye ball (Bell's phenomenon) does not occur during short blinks and only in about half of the subjects during voluntary unrestrained prolonged lid closure. Our evidence does not support the possibility that the transient eye movements during blinks are caused primarily by a mechanical interaction between the lids and the eye (or the scleral annulus). More likely, they are a secondary effect of an active cocontraction of extraocular muscles that primarily results in retraction of the eye. PMID- 4031979 TI - Adaptive response to ocular muscle weakness in human pursuit and saccadic eye movements. AB - Eye movement deficits caused by ocular muscle weakness vary according to the position of the eye in the orbit and the direction of eye movement. We studied the ability of both the saccadic and pursuit eye-movement systems to compensate for these anisotropic deficits in four patients with ocular muscle weakness. The eye-position dependence of each patient's motor deficit was characterized by plotting the position of the weak eye against that of the normal eye (in various orbital positions) when fusion was prevented, thus giving a static eye-position curve from which relative muscle strength could be inferred. Movements of the weak eye were smaller and slower than those made by the normal eye, so that the weak eye required more time to acquire a visual target. When patients were forced to view monocularly with their weak eye for several days, both the saccadic and pursuit systems showed changes in the movements of the normal eye consistent with an increased central innervation designed to decrease the time it takes to bring the target's image onto the fovea of the weak eye and to keep it there. These adaptive changes varied with eye position and movement direction and compensated for the weak muscle in both its agonistic and antagonistic actions. Saccadic adaptation consisted of a change in the relationship between saccadic amplitude and retinal error (distance between the target's image and the fovea) to compensate for hypometria (undershoot) and a readjustment of the ratio of the phasic (pulse) and tonic (step) components of the saccadic innervation to suppress postsaccadic ocular drift. Pursuit adaptation consisted of an increase in the relationship between eye acceleration and the rate of motion of the image of the target on the retina during the initial phase of tracking as well as an increase in the velocity during tracking of a target moving at a constant velocity. These changes reflect an increase in pursuit innervation that would cause the weak eye's velocity to approach target velocity sooner. The average acceleration of the normal eye during the initial period of tracking (130 ms) increased by as much as threefold. The corresponding maximum smooth eye velocity increased so that, for example, the pursuit response to a 15 degree/s target movement could be over 50 degree/s in the normal eye. PMID- 4031980 TI - Development of somatosensory responsiveness in the basal ganglia in awake cats. AB - Single-unit activity was recorded from the caudate nucleus (CD), globus pallidus, and entopeduncular nucleus (GP-ENTO) in awake, partially restrained kittens. The purpose of this experiment was to assess the ability of developing basal ganglia structures to process natural facial somatosensory information and compare this function to that observed in the adult. Somatosensory responsiveness in the CD and GP-ENTO developed slowly during the first three postnatal months. Somatosensory responsiveness had three major developmental trends in these nuclei: 1) The proportion of neurons responding to facial sensory stimulation increased with age; 2) proportionally, the area of face encompassing a receptive field of a neuron was smaller in adults than in young kittens; 3) qualitatively, adultlike responses to sensory stimulation did not appear until approximately three months of age. Units responsive to facial somatosensory stimulation in kittens under three months of age were very limited in the types of information they received. No specific stimuli parameters were encoded by these neurons. At approximately three months of age, units began to respond to varied stimuli (i.e., indentation of the skin as well as to brushing stimuli) and began to encode specific stimulus parameters such as direction of movement and relative location on the face. Kitten units responsive to skin indentation showed no evidence of encoding stimulus magnitude information. This was also true for the majority of adult basal ganglia neurons tested. The present findings suggest that the functions of the basal ganglia may be altered significantly during development. With increasing age, the basal ganglia may change from primarily a relay area for relatively nonspecific sensory information to an active processor of complex afferent information. PMID- 4031981 TI - Inferior olivary neurons in the awake cat: detection of contact and passive body displacement. AB - We have recorded from 306 neurons in the inferior olive of six alert cats. Most of the cats were trained to perform a simple task with the forelimb. We observed the neural responses to a wide variety of cutaneous and proprioceptive stimuli, as well as responses during spontaneous and learned active movements. Neurons responsive to somatosensory stimulation were found in all parts of the inferior olive, and they were roughly evenly divided between those responsive to cutaneous stimulation and those responsive to proprioceptive stimulation. In the dorsal accessory olive all neurons were responsive to somatosensory stimulation. In the medial accessory nucleus 88% and in the principal olive 74% of cells were responsive to somatosensory stimulation. Cells responsive to cutaneous stimulation usually had small receptive fields, commonly on the paw. These cells had low-threshold responses to one or more forms of cutaneous stimulation and typically fired one spike at the onset of the stimulus on 80% or more of stimulus applications. Cells responsive to proprioceptive stimulation most commonly responded to passive displacements of a limb. These cells were often very sensitive, responding to linear displacements of less than 1 cm in one specific direction. No cells in our sample responded reliably during active movement by the animal. Only 21% of cells responding to passive proprioceptive stimulation showed any modulation during active movement, and the modulation was weak. Likewise, cells responsive to cutaneous stimulation generally failed to respond when a similar stimulus was produced by an active movement by the animal. Exceptions to this were stimuli produced during exploratory movements or when the receptive field unexpectedly made contact with an object during active movement. Electrical stimulation applied in the inferior olive failed to evoke movements or to modify ongoing movement. Our results are consistent with the hypothesis that inferior olivary neurons function as somatic event detectors responding particularly reliably to unexpected stimuli. PMID- 4031982 TI - Comparison of response properties of cells in the cat's visual cortex at high and low luminance levels. AB - Receptive-field organization of cells in the cat's striate cortex and lateral geniculate nucleus (LGN) was investigated by using bars of light as stimuli. The aim was to determine if differences occur between conditions of high and low luminance levels. Of 72 cortical cells studied, the receptive fields of 63 were clearly different at high compared with low luminances. Units that gave on-off responses to flashed bars, for example, typically displayed on-only responses at low luminance. By far the most frequent change was that off responses were reduced or absent at low luminance levels. Of 63 cells that showed clear changes, 54 were of this type. This altered receptive-field organization appears to remain for extended periods (we have monitored the steady-state case for up to 2 h). Additional tests allow us to rule out the possible influence of overall changes in response strength and scattered light. To see if similar changes in receptive field organization are present at the level of the LGN, we recorded from a small number of cells in the LGN (n = 10) and from an additional five afferent fibers in the cortex. In each case, there was a change in center-surround organization between high and low luminance levels similar to that previously reported for retinal ganglion cells. The excitatory responses from the surround for both on center and off-center cells were absent at low luminance. Taken together, the results suggest that surround responses that can be elicited from ganglion cells and LGN cells make an important contribution to the receptive-field organization of cortical neurons. Changes in receptive-field organization of cortical cells are apparently not accompanied by alterations of other basic response properties. Orientation (7 cells) and spatial frequency (53 cells) selectivity remain relatively unchanged when measured at different luminances. Although optimal spatial frequency is slightly lower at low luminance levels, the low spatial frequency attenuation remains unaltered. Since receptive-field changes between high and low luminance levels suggest that a unit's classification may also vary, we examined simple and complex cell characteristics using sinusoidal gratings (65 cells). Contrary to what we had anticipated, the degree of modulation of responses was relatively independent of luminance, indicating that cell classification does not vary with stimulus luminance. PMID- 4031983 TI - T2-T5 spinothalamic neurons projecting to medial thalamus with viscerosomatic input. AB - Spinothalamic tract neurons projecting to medial thalamus (M-STT cells), ventral posterior lateral nucleus (VPL) of the thalamus (L-STT cells), or both thalamic regions (LM-STT cells) were studied in 19 monkeys anesthetized with alpha chloralose. Twenty-seven M-STT cells were antidromically activated from nucleus centralis lateralis, nucleus centrum medianum, or the medial dorsal nucleus. Stimulation of VPL elicited antidromic responses from 22 cells and 13 cells were activated from both VPL and medial thalamus. Antidromic conduction velocities of M-STT cells were significantly slower than those of L-STT or LM-STT cells. M-STT cells were located in laminae I, IV, V, and VII with greater numbers found in the deepest laminae. L-STT cells were located mostly in lamina IV, whereas most LM STT cells were found in lamina V. Twenty-four of 27 M-STT cells, all L-STT cells, and all LM-STT cells received input from both cardiopulmonary sympathetic and somatic afferent fibers. WDR cells were most common among the L-STT and LM-STT groups, whereas HT cells were the most common class in the M-STT cell group. Excitatory receptive fields of M-STT cells were large, and often bilateral. Receptive fields of L-STT cells were simple and never bilateral. Receptive fields of LM-STT cells could be similar to M-STT or L-STT cells. Thirty-three percent of the M-STT cells, 37% of the L-STT cells, and 62% of the LM-STT cells had inhibitory receptive fields. Inhibition was elicited most often by a noxious pinch of the hindlimbs. Sixteen of 23 (70%) M-STT cells received C-fiber cardiopulmonary sympathetic input in addition to A-delta-fiber input. The other 7 cells received only A-delta-fiber input. Only 45% of the L-STT cells and 38% of the LM-STT cells received both A-delta- and C-fiber inputs. The maximum number of spikes elicited by A-delta-input was related to segmental locations for L-STT cells with greatest responses in T2 and lesser responses in more caudal segments; however, no such trend was apparent for M-STT cells or for responses to C-fiber input for either group. Electrical stimulation of the left thoracic vagus nerve inhibited 7 of 18 M-STT cells, 10 of 16 L-STT cells, and 6 of 12 LM-STT cells. These results are the first description of visceral input to cells projecting to medial thalamus.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 4031984 TI - Topographic organization of interaural intensity difference sensitivity in deep layers of cat superior colliculus: implications for auditory spatial representation. AB - Sensitivity to interaural intensity difference (IID) was examined for 103 neurons in the deep layers of superior colliculus (SC) in ketamine barbiturate anesthetized cats. Noise stimuli were presented dichotically, and IID sensitivity functions were generated while keeping the average binaural intensity (ABI) of stimulation constant. Neurons of three binaural classes were found to be IID sensitive. Neurons receiving excitatory contralateral input and inhibitory ipsilateral input (EO/I cells, 55% of sample) had steplike IID functions, with maximum response at IIDs corresponding to contralateral azimuths (positive IIDs), total suppression at IIDs corresponding to ipsilateral azimuths (negative IIDs), and cutoffs at different positions along the IID axis for different neurons. Neurons responsive only to binaural stimulation (OO/F cells, 15% of sample) had IID functions with a sharp peak in the range of 0 to 10 dB IID. Cells receiving excitatory input contralaterally and a facilitatory ipsilateral input (EO/F cells, 7% of sample) had IID functions of intermediate shape, with a peak in the range of 10 to 20 dB IID and a sharper cutoff near zero IID than at larger positive IIDs. The sharpness of IID cutoff for EO/I cells was quantified by measuring an 80% IID dynamic range. Neurons with 80% IID dynamic ranges of less than 26 dB were judged to have sharp cutoffs. The position along the IID axis of the IID cutoff for these cells was quantified by recording the IID at which the response was at 50% of maximum (half-maximal IID). A topographic organization of EO/I cells with sharp IID cutoffs was found along the rostrocaudal axis of SC, such that rostral EO/I cells had IID functions with half-maximal IIDs near zero, while increasingly caudal EO/I cells had progressively larger (positive) half maximal IIDs. Although detailed maps could not be obtained in individual animals, the topography was observed in each of nine experiments in which EO/I cells were located in two or more rostrocaudal locations (P = 0.00002). The effect of stimulus level on the stability of IID cutoff was examined for 13 EO/I cells. The majority (85%) showed less than 10 dB variation in half-maximal IID across a range of suprathreshold ABIs, indicating that EO/I cells in SC generally exhibit stability in cutoff with changes in intensity of broadband stimuli.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 4031985 TI - Convergence of hepatic osmoreceptive inputs on sodium-responsive units within the nucleus of the solitary tract of the rat. AB - Single-shock electrical stimulation of the hepatic branch of the vagus induced both facilitation and suppression in units within the nucleus of the solitary tract (NTS). Some units that were facilitated by electrical stimulation also increased their discharge rates during topical iontophoretic application of Na+, as well as portal infusion of hypertonic saline. Other facilitatory units produced opposite responses; their discharge rates decreased during topical iontophoretic application of Na+ and portal infusion of hypertonic saline. Some units that were suppressed by electrical stimulation also responded to the topical application of Na+ and portal infusion of hypertonic saline. The responses to these two different stimuli were positively correlated in some units but not in others. The evidence suggests that the units within the NTS that are responsive to hepatic osmosensitive primary afferents may serve a Na+-responsive function and may be important in integration within the NTS for isosmotic or isovolemic homeostasis. PMID- 4031986 TI - Properties of visceral primary afferent neurons in the nodose ganglion of the rabbit. AB - The active and passive membrane properties of rabbit nodose ganglion cells and their responsiveness to depolarizing agents have been examined in vitro. Neurons with an axonal conduction velocity of less than 3 m/s were classified as C-cells and the remainder as A-cells. Mean axonal conduction velocities of A- and C-cells were 16.4 m/s and 0.99 m/s, respectively. A-cells had action potentials of brief duration (1.16 ms), high rate of rise (385 V/s), an overshoot of 23 mV, and relatively high spike following frequency (SFF). C-cells typically had action potentials with a "humped" configuration (duration 2.51 ms), lower rate of rise (255 V/s), an overshoot of 28.6 mV, an after potential of longer duration than A cells, and relatively low SFF. Eight of 15 A-cells whose axons conducted at less than 10 m/s had action potentials of longer duration with a humped configuration; these were termed Ah-cells. They formed about 10% of cells whose axons conducted above 2.5 m/s. The soma action potential of A-cells was blocked by tetrodotoxin (TTX), but that of 6/11 C-cells was unaffected by TTX. Typically, A-cells showed strong delayed (outward) rectification on passage of depolarizing current through the soma membrane and time-dependent (inward) rectification on inward current passage. Input resistance was thus highly sensitive to membrane potential close to rest. In C-cells, delayed rectification was not marked, and slight time dependent rectification occurred in only 3 of 25 cells; I/V curves were normally linear over the range: resting potential to 40 mV more negative. Data on Ah-cells were incomplete, but in our sample of eight cells time-dependent rectification was absent or mild. C-cells had a higher input resistance and a higher neuronal capacitance than A-cells. In a proportion of A-cells, RN was low at resting potential (5 M omega) but increased as the membrane was hyperpolarized by a few millivolts. A-cells were depolarized by GABA but were normally unaffected by 5-HT or DMPP. C-cells were depolarized by GABA in a similar manner to A-cells but also responded strongly to 5-HT; 53/66 gave a depolarizing response, and 3/66, a hyperpolarizing response. Of C-cells, 75% gave a depolarizing response to DMPP.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 4031987 TI - Activation of dorsal horn cells by ventral root stimulation in the cat. AB - Responses of dorsal horn cells to ventral root stimulation were determined for the L7 and S1 levels of the spinal cord of 14 anesthetized cats. Forty-six dorsal horn cells were found that were excited by stimulation of the distal stump of the cut ventral root. For maximum excitation it was necessary to use a train of stimuli. For the 34 dorsal horn cells whose peripheral receptive-field properties could be characterized, 14 were wide dynamic range cells and 19 were high threshold cells. The other cell responded exclusively to stimulation of deep tissue. None of the cells responded exclusively to innocuous stimuli, and all responded more vigorously to noxious than to innocuous stimuli. Some cells also responded to noxious heat applied to the skin of the receptive field. Locations of 10 of the activated dorsal horn cells were identified. They were distributed throughout the dorsal horn, but most were found in laminae V and VI. In four animals, both the proximal and distal stumps of the cut S1 ventral root were stimulated while searching for dorsal horn cells. Ten dorsal horn cells were found that were excited by stimulation of the distal stump of the ventral root. No cells were found that responded to proximal stump stimulation. To prevent current spread by stimulation of the ventral root, an extra ground electrode was placed distal to the stimulating electrodes. When the ground electrode was removed, distinctive signs of current spread appeared in that a cord dorsum potential could be recorded and the dorsal horn neuronal responses changed. Dorsal horn neurons could also be excited by nonelectrical stimuli such as crushing the ventral root. If the ventral root was crushed distal to the stimulating electrodes, however, the initially excited cell could no longer be activated by ventral root stimulation. Activation of dorsal horn cells by stimulation of the distal stump of a cut ventral root was abolished when the dorsal root of the same segment was sectioned. Conduction velocities of the fibers in the ventral root that excited dorsal horn cells ranged between 0.25 and 1.78 m/s with a mean of 0.91 +/- 0.47 (SD) m/s. These results show that there are unmyelinated afferent fibers in the ventral root that enter the spinal cord through the dorsal root and excite dorsal horn cells.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 4031988 TI - Color cell groups in foveal striate cortex of the behaving macaque. AB - Color-tuning curves were obtained for 218 cells in the foveal striate cortex of behaving macaques. Each cell was tested with its optimal spatial stimulus. Test colors (14 interference filters, 4 Wratten filters, and white) were matched for human photopic luminosity and presented at luminance levels sufficient to induce vigorous responding from most cells. One hundred eighty-four cells were selected for further analysis on the basis of a color-tuning index. Of these, 130 with tuning curves that correlated well (0.9 or better) with other tuning curves were studied in detail. Individual cells were found with peak responses to every color tested. Sixty-three tuning curves fell into the six largest cross-correlation groups, containing 15, 14, 12, 9, 7, and 6 cells, with mean tuning-curve peaks at 450, 656, 656, 506, 577, and 506 nm, respectively. Cross-correlation groups having the same peak location (656 nm, 506 nm) were distinguishable on the basis of tuning-curve width. Response patterns, cone input estimates, and comparison with human psychophysics suggest that two of these cell groups function as an opponent pair processing the colors red and green. Two other cell groups process the colors blue and yellow but show less well-developed opponency. Microdrive depth readings, correlated with histological lesion sites, show these "red," "green," "blue," and "yellow" cells to be most common in layer 4 of the striate cortex. PMID- 4031989 TI - Mixing of color signals by turtle cone photoreceptors. AB - The direct mixing of red and green cone signals in the outer plexiform layer of the turtle retina was studied by using intracellular recordings from red cone photoreceptors. Cone photoresponses were a function of the wavelength of the photons that stimulated them, even when small-diameter stimuli were used. The intensity response curves measured with red and green test flashes had different shapes. The kinetics of approximately equal amplitude red and green responses also differed. To quantify the short wavelength input onto red cones, differential chromatic adaptation was used. The relative sensitivity of the red cone to red and green test flashes was a function of the color and intensity of the background illumination; red backgrounds decreased relative red sensitivity, and green backgrounds increased relative red sensitivity. The spectral sensitivity of the additional short wavelength input onto red cones was determined by using differential chromatic adaptation, and was found to peak approximately 550 nm. We conclude that red cones receive an additional excitatory input from green cones (and possibly blue cones). A model of the cone mosaic suggests that approximately 50% of the red cone response (linear range) to a dim green test flash arises from neighboring green cones. PMID- 4031990 TI - Electron microscopy of Golgi-impregnated photoreceptors reveals connections between red and green cones in the turtle retina. AB - Red and green cones of two turtle species (Pseudemys scripta elegans and Chelydra serpentina) retina have been stained with Golgi procedures and examined by light microscopy of whole-mount tissue and by electron microscopy of serial thin sections. By light microscopy, red and green single cones appear indistinguishable, but double cones can be readily identified. All Golgi-stained photoreceptors in turtle retina have a spray of telodendria radiating from their synaptic pedicles. The telodendria of single cones are 10-20 micron long and end in clusters of terminals, whereas double cones have 30- to 50-micron long telodendria in addition to a very short bush of telodendria arising from one side of the pedicle. Electron microscopy of the Golgi-stained cones allows them to be distinguished into red or green spectral types by the appearance of their oil droplets. Furthermore, the spectral identity of cones contacted by the telodendria of identified Golgi-stained cones can similarly be determined. Red single cones make telodendrial contacts with other red singles, both members of the double cones, and with green single cones. Green single cones likewise connect to many surrounding red cones, both single and double types, and a few other green singles. Both members of the double cone connect to neighboring red and green singles and occasionally to double cones. The telodendria of stained cones end on spectrally homologous or heterologous cone types at basal junctions, central elements of ribbon synapses or, sometimes, as lateral elements of ribbon synapses. However, all these synaptic contacts appear to be of the same type, i.e., narrow-cleft basal junctions. Small gap junctions occur between neighboring cone pedicles, regardless of spectral type, in the visual streak area of the retina. Large gap junctions occur between unidentified cone telodendria in the neuropil of the outer plexiform layer. The telodendrial connections between red and green cones in the turtle retina have the appearance of chemical synapses and suggest an anatomical pathway responsible for the mixing of red and green signals in red or green cones of the turtle retina as reported in the accompanying physiological paper by Normann, Perlman, and Daly (27). PMID- 4031991 TI - Interactions between rostral pontine and ventral medullary respiratory neurons. AB - Lesioning studies have demonstrated that the respiratory rhythm is generated within the brain stem and that connections between the pons and the medulla must be intact for the generation of eupneic breathing in the decerebrate or anesthetized vagotomized cat. However, the nature of proposed functional connections between pontine and medullary respiratory neurons is not well understood. The possibility of interactions between respiratory neurons of the rostral pons (n. parabrachialis medialis, Kolliker-Fuse nucleus) and the ipsilateral ventral respiratory group (VRG; n. retroambigualis, n. ambiguus, retrofacial nucleus) was investigated because of neuroanatomical and electrophysiological evidence for such connections. Phrenic nerve activity and pontine and medullary single-unit respiratory related activities were recorded extracellularly in 44 decerebrate, vagotomized, paralyzed, and artificially ventilated cats. Cross-correlation analysis was employed to detect and evaluate functional associations of pairs of cells. Eighteen (7%) of the 255 pairs of respiratory neurons analyzed showed evidence of short time scale correlations indicative of a functional interaction. The interpretations of the detected correlations suggest that some cell pairs were correlated due to mono- or paucisynaptic connections, while others were correlated due to the influence of an unobserved shared input. The interpretations for 11 of the 15 cell pairs for which a monosynaptic connection may be postulated involve a projection from a tonically active respiratory neuron. Twelve of the 18 positive correlations involved neurons whose maximum rates of discharge occurred during different parts of the respiratory cycle. The results of this study provide the first evidence of functional connections among pontine and medullary respiratory neurons based on the evaluation of simultaneously recorded spike trains and suggest that the role of the rostral pontine respiratory neurons in the control of the respiratory rhythm may be mediated by various types of interactions. When considered with the results of other studies, our data suggest that monosynaptic interactions between VRG and rostral pontine respiratory neurons play a limited role in the control of the respiratory cycle in the decerebrate vagotomized cat. It is likely that the influence of the pons on ventral medullary neurons (and vice-versa) is also exerted via polysynaptic pathways and/or via brain stem neurons not sampled in this study. PMID- 4031992 TI - Spontaneous and driven responses of semicircular canal primary afferents in the unanesthetized pigeon. AB - Spontaneous activity from 120 vestibular semicircular canal (SC) primary afferents and driven responses from 20 SC primary afferents to 2.3-decade bandwidth (0.029-6.152 Hz) sum of sinusoidal angular rotations were characterized in 10 unanesthetized pigeons. The results were compared with those previously gathered from barbiturate anesthetized pigeons. The average spontaneous mean firing rate (MFR) of SC primary afferents in unanesthetized pigeons was found to be 168 impulses per second (I/s), n = 120, and is approximately 80% higher than that for SC primary afferents in anesthetized pigeons [93 I/s, n = 149 (Ref. 9) and 92 I/s, n = 124 (Ref. 22)]. The spontaneous discharge of SC primary afferents from unanesthetized pigeons was classified according to the coefficient of variation (CV) of 512-1,024 interspike intervals (ISIs) into regular (CV less than 0.1), intermediate (0.1 less than or equal to CV less 0.4), and irregular (0.4 less than or equal to CV) categories. The percentages of SC primary afferents falling within each CV category were similar for unanesthetized and anesthetized pigeons (22). The relation between the spontaneous mean ISI and its standard deviation (SD) for SC primary afferents in the unanesthetized pigeon is best described by a power function model, which provides a significantly better fit than does a linear model. The parameters of this power function model are similar for SC primary afferents in unanesthetized and anesthetized pigeons (10). The spontaneous ISIs of individual SC primary afferents in the unanesthetized pigeon were found to be distributed either normally, log-normally, or according to the first passage time of the Wiener-Levy (WL) process. The gain of anterior SC primary afferents at 0.25 Hz is similar for anesthetized (2.93 I X s-1 X deg-1 X s-1, n = 14) (11) and for unanesthetized (3.01 I X s-1 X deg-1 X s-1, n = 14) pigeons. Bode plots constructed from the responses to sum sinusoidal angular accelerations reveal that SC primary afferents in unanesthetized pigeons display a phase lead and gain enhancement at frequencies between 0.6 and 6 Hz.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 4031993 TI - Action of the efferent vestibular system on primary afferents in the toadfish, Opsanus tau. AB - Spinalized toadfish were held in a lucite chamber and perfused through the mouth with running seawater. Primary vestibular afferents and vestibular efferent axons and somas were studied with glass microelectrodes. Vestibular semicircular canal afferent and efferent axons were visually identified and penetrated with glass microelectrodes. Afferents responded to pulses of injected current with trains of action potentials, whereas efferents responded with only a single spike. This differential response to injected current served to further distinguish these two classes of nerve fibers that share the same canal nerve for part of their course. When current pulses were injected into efferent somadendritic recording sites, cells responded with trains of action potentials similar to those seen in other central nervous system neurons. Semicircular canal afferents were spontaneously active and occupied the same spectrum of regularity as vestibular afferents recorded in other species. Behavioral arousal evoked by lightly touching the fish on the snout or over the eye resembled spontaneous arousal observed in the field and consisted of eye withdrawal, fin erection, and attempted swimming. Efferent vestibular neurons were spontaneously active and increased their frequency of discharge when the fish was behaviorally aroused. Most efferents were briskly activated by behavioral arousal, but the time constant of the decay of their responses was variable ranging from 100 to 600 ms. Not only touch, but multimodal stimuli were capable of increasing the level of spontaneous activity of efferent vestibular neurons. The shortest latency to behavioral activation was 160 ms. Vestibular primary afferents also manifested increase in neuronal activity with behavioral activation. Irregularly discharging afferents were much more responsive than regularly discharging afferents. One rare case of transient inhibition in a regularly discharging afferent is illustrated. Severing the efferent vestibular nerve blocked behavioral activation in vestibular primary afferents. Electrical stimulation of the efferent vestibular nerve produced excitatory postsynaptic potentials (EPSPs) at latencies within the monosynaptic range in vestibular primary afferents. These monosynaptic EPSPs could produce action potentials in primary afferents or could sum with subthreshold depolarizations produced by current passed through the microelectrode to initiate impulses.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 4031994 TI - Reflex control of dynamic muscle stiffness in a slow crustacean muscle. AB - The properties of a stretch reflex in the ventral superficial muscle of the hermit crab abdomen were studied in an isolated abdominal preparation to determine how the reflex affects the mechanical properties of the muscle and whether the reflex is controlling length, force, or stiffness. The reflex was elicited by stretch of hypodermal mechanoreceptors in the cuticle and resulted in the activation of excitor motoneurons to both circular and longitudinal layers of the muscle, thus stiffening the abdomen. The medial motoneuron of the longitudinal layer of the right fourth segment was selected for detailed analysis. It was tonically active and responded to stretch with a phasic burst having a latency of 100 ms. Reflex muscle tension began to increase at 130 ms and reached a peak at 300 ms. Reflex-burst frequency increased slightly with stretch amplitude. Peak force was an approximately linear function of stretch amplitude. No tonic component to the reflex was found in the medial motoneuron, in the central motoneuron (the smallest excitor to the muscle), or in the medial motoneuron studied in intact animals. The reflex-burst frequency was a function of stretch velocity, increasing between two and one-half to four times for a 10 fold increase in stretch velocity. Peak force was essentially independent of stretch velocity over this range. The reflex-burst frequency was not a function of the initial length of the muscle on the ascending limb of the length-tension relation. Active peak force (between two and three times passive peak force) was relatively constant over this range. The dynamic active stiffness (the resistance to stretch of the muscle when the nervous system was intact) was separated into two components. One component is that due to the tonic frequency of the motoneurons, the other to the reflex burst. The reflex component makes up a substantial part of the total active stiffness. Dynamic active stiffness is relatively constant under the conditions of these experiments and, when normalized, is similar to that observed in mammalian myotatic reflexes. This constancy, however, cannot be due to negative feedback control of stiffness, as in mammals. It is suggested that constant reflex stiffness arises from the combination of the low-pass filter characteristics of the muscle and the high pass filter characteristics of the reflex over a restricted range of velocities.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 4031995 TI - Dynamic control of the perioral system during speech: kinematic analyses of autogenic and nonautogenic sensorimotor processes. AB - Afferent contributions to the motor control of speech were evaluated by applying unanticipated loads to the lower lip during the combined upper lip-lower lip gesture associated with the oral closing movements for a "b" sound. Loads were introduced randomly in approximately 15% of the trials to minimize subject anticipation or adaptation. A total of 490 load trials (in five naive subjects) were distributed within a restricted interval (100 ms) centered on the initiation of agonist muscle contraction associated with the lip-closing movements. Kinematic adjustments of the upper and lower lips to these perturbations were examined in detail. In all subjects, load-induced changes in upper and lower lip displacement, movement time, and closing velocity were statistically significant and observed the first time a perturbation was introduced. Load timing variations within the target interval resulted in systematic changes in the site of the compensatory adjustments (upper versus lower lip) and in the magnitude of the kinematic responses. These kinematic changes appeared to reflect the dynamic nature of underlying control processes and clearly contrasted the different response characteristics of autogenic (lower lip) and nonautogenic (upper lip) compensatory actions. Although both upper and lower lip adjustments contributed to perturbation compensations, autogenic responses were found to predominate when loads occurred 20-55 ms before muscle activation. For these early loads, autogenic responses provided approximately 75% of the total compensation. For later loads, when the evolving speech motor action was more time constrained, nonautogenic (open-loop) compensations predominated, providing approximately 65% of the total compensation. The variations in upper and lower lip compensatory response magnitude did not parallel the time course of facial muscle activation. Lower lip kinematic adjustments were reduced 10-15 ms prior to the onset of agonist muscle activation, whereas upper lip adjustments increased in magnitude 10-20 ms after agonist onset. Apparently the dynamic modulation of these responses is controlled independently from facial motoneuron excitation, possibly involving sensorimotor processing via supranuclear centers. Overall the compensatory movement displacements were highly related to the magnitude of the perturbation displacement, especially for loads introduced prior to agonist muscle onset, reflecting a well-calibrated readjustment.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 4031996 TI - Influence of the globus pallidus on arm movements in monkeys. III. Timing of movement-related information. AB - Monkeys were trained to make a visually triggered arm-reaching movement to a lighted button in a simple reaction-time paradigm, during which the reaction time (RT) and movement time (MT) were measured. Stimulus trains of varying duration were applied at various times before and during the movement at locations in the globus pallidus where application of long stimulus trains caused increased MTs. A critical stimulus period was identified during which stimulus application effectively prolonged MTs. The activity of pallidal neurons was examined during performance of the same behavioral task. More than 60% of the neurons examined showed task-related changes in activity that began before or during the reaching movement. For 45% of these cells, the initial change in firing occurred during the critical stimulus period, 50-150 ms before mechanically detected movement. Comparison of the critical stimulus period, the time of task-related changes in the discharge of pallidal neurons, and the time of EMG activity in muscles acting at the back, shoulder, elbow, and wrist revealed that both the critical stimulus period and changes in neuronal discharge occurred at or after initial muscle activation and during the buildup of EMG activity. These data are consistent with a model in which the globus pallidus plays a role in scaling the magnitude of muscle activity that determines movement velocity without affecting the initiation or sequential organization of the programmed motor output. PMID- 4031997 TI - FMRF-amide-like substances in the leech. II. Bioactivity on the heartbeat system. AB - In the preceding paper (Kuhlman, J. R., C. Li, and R. L. Calabrese (1985) J. Neurosci. 5: 2301-2309) FMRF-amide-like immunoreactivity was localized to a specific set of neurons in the leech. Three types of these neurons are involved in controlling the animal's heartbeat: HE motor neurons and HA modulatory neurons which directly innervate the hearts, and the swim-initiating interneurons (cells 204) which can accelerate the heartbeat central pattern generator. Application of synthetic FMRF-amide had effects on the hearts and the heartbeat central pattern generator that mimicked the actions of the HA and cell 204 neurons. Bath application of FMRF-amide (10(-7) to 10(-6) M) to the hearts activated their myogenic rhythm and increased their beat tension, thus mimicking the effects of activity in HA cells. Bath application of lower concentrations of FMRF-amide (10( 9) to 10(-8) M) to the isolated central nervous system dramatically accelerated the central motor program for heartbeat, thus mimicking the effects of activity in cell 204. These observations suggest that an FMRF-amide-like substance may be used as a chemical signal by HA and cell 204 neurons. The role of the FMRF-amide like substance contained in HE motor neurons remains unclear, but it may be released along with the HE cell's neuromuscular transmitter, acetylcholine. PMID- 4031998 TI - Kinematic features of unrestrained vertical arm movements. AB - Unrestrained human arm trajectories between point targets have been investigated using a three-dimensional tracking apparatus, the Selspot system. Movements were executed between different points in a vertical plane under varying conditions of speed and hand-held load. In contrast to past results which emphasized the straightness of hand paths, movement regions were discovered in which the hand paths were curved. All movements, whether curved or straight, showed an invariant tangential velocity profile when normalized for speed and distance. The velocity profile invariance with speed and load is interpreted in terms of simplification of the underlying arm dynamics, extending the results of Hollerbach and Flash (Hollerbach, J. M., and T. Flash (1982) Biol. Cybern. 44: 67-77). PMID- 4031999 TI - Is a nicotinic influence involved in denervation-induced depolarization of muscle? AB - The neurotrophic role of acetylcholine (ACh) in the denervation-dependent decline of muscle resting membrane potential (RMP) was evaluated. Freshly dissected rat hemidiaphragms with short or long (2 cm) nerve stumps attached ("-N" and "+N" preparations, respectively) were incubated in organ culture in the presence or absence of the nicotinic blockers, alpha-bungarotoxin (alpha-BTX) or d tubocurarine (curare). Subsequently, RMPs and miniature endplate potentials (MEPPs) of the junctional region were measured. Spontaneous MEPPs disappeared with a half-life of 12 and 20 hr in -N and +N preparations, respectively. A 10- to 15-mV depolarization of RMP was observed between 15 and 20 hr in -N muscles and between 24 and 28 hr in +N muscles. This time course of disappearance of spontaneous potentials and of membrane depolarization agrees well with that observed in vivo. Although nicotinic transmission was blocked from the initiation of the incubation period in alpha-BTX- or curare-treated muscles, no acceleration of RMP decline in -N muscles in vitro was observed. Moreover, in +N preparations the effect of the nerve stump in delaying RMP depolarization persisted despite the continuous presence of alpha-BTX or curare. Since excess ACh triggers a lysosomal proteolytic response at the nerve-muscle junction and since this may occur early in denervation, the possible role of a nicotinic-induced proteolytic mechanism was tested in vitro with the potent protease inhibitor leupeptin. This inhibitor did not delay or prevent the denervation-dependent alterations.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4032000 TI - Growth cone morphology and trajectory in the lumbosacral region of the chick embryo. AB - We quantitatively analyzed several features of orthogradely labeled peripheral growth cones in the lumbosacral region of the chick embryo. We compared motoneuron growth cones in regions where they appear to express specific directional preferences (the plexus region and regions where muscle nerves diverge from main nerve trunks), which we operationally defined as "decision regions," to motoneuron growth cones in other pathway regions (the spinal nerve, nerve trunk, and muscle nerve pathways) which we termed, for contrast, "non decision region." We found that motoneuron growth cones are larger, more lamellepodial, and have more complex trajectories in decision regions. Sensory growth cone populations, which are thought to be dependent upon motoneurons for outgrowth (Landmesser, L., and M. Honig (1982) Soc. Neurosci. Abstr. 8: 929), do not enlarge or become more lamellepodial in motoneuron decision regions, suggesting that this local environment does not affect all species of growth cones equally and that the alterations in motoneuron growth cones in these regions may be relevant to their specific guidance. In addition, the resemblance between the sensory population and other closely fasciculating growth cones lends support to the suggestion that sensory neurons utilize motoneuron neurites as a substratum. We suggest that the convoluted trajectories, enlarged size, and more lamellepodial morphology of motoneuron growth cones in decision regions is either related directly to the presence of specific cues that guide motoneurons or to some aspect of this environment that allows them to respond to specific cues. PMID- 4032001 TI - Estrogen and progestin receptors appear in transplanted fetal hypothalamus preoptic area independently of the steroid environment. AB - Sexual maturation and differentiation of the rat brain are believed to result from the interaction of gonadal steroids with specific neural receptors during late fetal and early postnatal life. A variety of evidence indicates that the first appearance of estrogen receptors in the hypothalamus-preoptic area (HPOA) during the perinatal period is a crucial evident underlying these processes. However, it is unknown to what extent the ontogeny of estrogen receptors is itself influenced by gonadal steroids present in the fetal environment. In order to address this question, estrogen receptors were assayed in HPOA 8 weeks after transplantation of the tissue from embryonic day 15 to 18 fetuses to either the choroidal pia overlying the superior colliculus or to the anterior chamber of the eye of adult female hosts. Host animals were either intact or ovariectomized and adrenalectomized, with or without estrogen replacement. The saturable binding of estradiol to cytosol of HPOA transplants exhibited the steroid specificity and high affinity characteristic of authentic estrogen receptors. No differences in the level of cytosol estrogen receptors in transplanted HPOA grown in the presence or absence of gonadal steroids were found. Receptor concentrations were also similar in HPOA taken from male or female fetuses. Autoradiography with [3H]estradiol revealed clusters of estrophilic cells in the transplants similar to those of the adult host hypothalamus, again regardless of whether the transplant developed in the presence of gonadal steroids. Estrogen receptors from both groups were also found to be biochemically functional as indicated by the ability of acute estrogen treatment to induce progestin receptors in the transplants.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4032002 TI - Monoclonal antibodies reveal novel aspects of the biochemistry and organization of olfactory neurons following unilateral olfactory bulbectomy. AB - Following unilateral olfactory bulbectomy in rats the ipsilateral olfactory neuroepithelium undergoes degeneration. Subsequently, the receptor neuron complement of the tissue is restored by the proliferation and differentiation of immature neuroblasts. However, as noted by other workers, in the absence of a target organ the dynamics of neuron regeneration is altered such that there is an overall reduction in the number of cells positive for the olfactory marker protein when cellular equilibrium is re-established. Immunocytochemical staining of the olfactory epithelium of unilaterally bulbectomized rats with a series of anti-neuronal monoclonal antibodies reveals an attenuation of binding of some antibodies to the neurons of the ipsilateral epithelium. In contrast, other anti neuronal monoclonal antibodies show no difference in staining intensity when ipsilateral and control contralateral epithelia are compared. These data suggest that the expression of some neuronal antigens is subject to control by the target olfactory bulb, whereas others are independent of such putative regulation. Besides altering the expression of some antigenic determinants, olfactory bulbectomy also results in certain organizational changes in epithelium. First, bulbectomy produces an increase in the incidence of a cell type that appears to span the neuroepithelium. Although the morphology of these cells is more akin to a sustentacular cell than to a receptor neuron, they are not immunoreactive with antibodies to sustentacular cells. The cells are stained, however, by an anti neuronal antibody, NEU-9. The second aspect of altered organization is the appearance of novel olfactory marker protein-positive structures in the olfactory mucosa.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4032003 TI - Quantitative in vivo receptor binding. II. Autoradiographic imaging of muscarinic cholinergic receptors. AB - The in vivo distribution of [3H]scopolamine in rat brain following establishment of constant, saturating arterial tracer concentrations was examined with the use of quantitative autoradiography. The equilibrium drug distribution, studied 240 min after initiation of tracer infusion, was highly correlated with the regional density of muscarinic receptor sites determined in vitro in the same animals by autoradiographic analysis of [3H]quinuclidinyl benzilate binding. Brain regions of highest receptor density were generally correlated with known terminal fields of cholinergic neurons, and they demonstrated a protracted time course of in vivo labeling. An exception was noted in the basal pons, where a receptor population of high density without documented cholinergic innervation was rapidly labeled. It is suggested that synaptic muscarinic receptors are labeled slowly, as a consequence of either restricted tracer accessibility or competition between tracer and endogenous acetylcholine for available binding sites, and that the pontine receptors may be functionally distinct from those in other brain regions. The in vivo equilibrium binding technique used in the present study results in regional tissue radioligand concentrations directly proportional to receptor density and may, thus, provide a basis for receptor imaging in the human brain by means of positron emission tomography. PMID- 4032004 TI - Dissociated neurons regenerate into sciatic but not optic nerve explants in culture irrespective of neurotrophic factors. AB - Explants of adult or 10-day-old rat sciatic and optic nerves were implanted as "bridges" through a silicon grease seal in a three-compartment chamber culture system, leading from a narrow center chamber to two adjacent side chambers. Dissociated newborn rat sympathetic or sensory neurons were plated into the center chamber and grown in the presence of optimal concentrations of nerve growth factor (NGF). By light microscopy, nerve fibers were seen to grow out of the sciatic nerve explants in the side chambers after 2 to 3 weeks. Electron microscopy showed large numbers of axons present inside the sciatic nerves, irrespective of the presence and number of living Schwann cells. Besides their tendency to fasciculate, axons grew with high preference on Schwann cell membranes and the Schwann cell side of the basal lamina, a situation identical to in vivo regeneration. In contrast to the sciatic nerves, no axons could be found under any condition in the optic nerves. This result points to the existence of extremely poor, non-permissive substrate conditions in the differentiated optic nerves which cannot be overcome by the strong fiber outgrowth-promoting effects of NGF. PMID- 4032005 TI - gamma-Aminobutyric acid- and benzodiazepine-induced modulation of [35S]-t butylbicyclophosphorothionate binding to cerebellar granule cells. AB - t-Butylbicyclophosphorothionate (TBPS) is a bicyclophosphate derivative with potent picrotoxin-like convulsant activity that binds with high affinity and specificity to a Cl- channel-modulatory site of the gamma-aminobutyric acid (GABA)/benzodiazepine receptor complex. Using intact cerebellar granule cells maintained in primary culture, we have studied the modifications induced by GABA and diazepam on the ion channel-modulatory binding site labeled by [35S]TBPS. At 25 degrees C, and in a modified Locke solution, the [35S]TBPS specific binding, determined by displacing the radioligand with an excess (10(-4) M) of picrotoxin, was approximately 70% of the total radioactivity bound to the cells. [35S]TBPS specific binding was saturable with a Kd of approximately 100 nM, a Bmax of approximately 440 fmol/mg of protein, and a Hill coefficient of 1.18. Neither cerebellar astrocytes maintained in culture for 2 weeks nor a neuroblastoma cell line (NB-2A) exhibited any specific [35S]TBPS binding. Muscimol (0.3 to 5 microM) enhanced and bicuculline (0.1 to 5 microM) inhibited [35S]TBPS specific binding to intact cerebellar granule cells. The effect of muscimol and bicuculline on [35S]TBPS binding was noncompetitive. Muscimol (0.1 to 5 microM) reversed bicuculline inhibition in a dose-dependent fashion but failed to reverse picrotoxin-induced inhibition. [35S]TBPS binding was also modulated by benzodiazepine receptor ligands. The binding was increased by diazepam and decreased by 6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylic acid methylester. Muscimol (0.05 microM) failed to reverse bicuculline inhibition in the absence of diazepam, but it became effective in the presence of 0.1 to 1 microM diazepam.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4032006 TI - Effects of body weight, adrenal status, and estrogen priming on hypothalamic progestin receptors in male and female rats. AB - Some laboratories have reported sex differences in the effect of estrogen priming on neural progestin receptor concentration, whereas others find no such differences. The present studies sought to identify experimental variables which might differentially influence the measurable level of hypothalamic cytosol progestin receptors in adult male and female rats. The influence of three variables, body weight, adrenal status, and estrogen priming regimen, was evaluated. Treatment with low doses of estrogen (2 or 8 micrograms of estradiol benzoate (EB) 48 hr before sacrifice) was slightly but not significantly more effective in elevating hypothalamic progestin receptor content in age-matched females than in males despite the 40% greater body weights of males. When the same doses of EB were administered per 200 gm of body weight to animals with and without adrenal glands, both basal and estrogen-induced levels of hypothalamic progestin receptor were significantly higher in adrenalectomized/gonadectomized rats than in rats which were gonadectomized only, regardless of sex. There was no significant effect of sex or any interaction between sex, adrenal status, or estrogen priming dose. The only significant sex difference in brain progestin receptors occurred when weight-matched males and females received multiple injections of higher priming doses of estrogen (three daily injections of 10 micrograms of EB). Under these conditions, females showed up to 2-fold higher levels of hypothalamic progestin receptors than males, regardless of adrenal status. These data suggest that sex differences may exist in the neural progestin receptor systems of male and female rats, but the relationship of these differences to sex differences in neuroendocrine function or behavior is not clear. PMID- 4032007 TI - The electrical circuitry of an olfactory sensillum in Antheraea polyphemus. AB - The aim of this study was to obtain a better insight into the distribution of active and passive electrical properties of the membranes of al olfactory sensillum. Such a sensillum is composed of three accessory cells which envelope the somata of two receptor neurons which have long (300 micron) dendrites that are incorporated in cuticular protuberances (hairs). An electrical equivalent circuit of this organ is reconstructed which is based upon the response of sensilla to current transients, the shape of extracellularly recorded spikes, and the effects of lesions on these signals. A strong influence of membrane capacitances on the overall response and on the shape of spikes becomes apparent. From the combination of electrical and morphometric data it follows that the resistance of the apical membranes of the accessory cells in much higher than the resistance of their basolateral membranes. Neither in simultaneous tip and sidewall recordings nor in the hair (dendrite) amputation experiments could antidromic propagation of action potentials into the dendrite be demonstrated. The commonly accepted retrograde propagation explanation for the biphasic waveform of the spike is, therefore, rejected. Dendrite amputation experiments showed that the impedance of the dendrite does not limit the spike amplitude and that the dendrite contributes slightly to the duration of the positive phases of spikes. Both of these observations indicate that the dendrite is also involved in the generation of the leading phase of the spike. Consequently the proposition is made that action potentials are initiated at a dendritic location. PMID- 4032008 TI - Local order among the dendrites of an amacrine cell population. AB - The cholinergic amacrine cells of the rabbit retina branch within a narrow stratum of the retina's inner synaptic layer, and their dendritic fields overlap as much as 70-fold. Because each cell's dendrites have many branches, the overlap must create a dense meshwork of cholinergic dendrites. To learn how the overlapping dendrites are positioned with respect to each other, we filled the dendrites of groups of neighboring cells with Lucifer Yellow CH. The cholinergic amacrine cells were selectively stained by intraocular injection of the fluorescent molecule 4,6-diamidino-2-phenylindole. The retinas were then fixed with 2% paraformaldehyde and 0.01% glutaraldehyde. The stained cells were penetrated under visual control by Lucifer Yellow-filled micropipettes. A systematic arrangement of the dendrites was observed. When a pair of cells was injected, their dendrites were often seen to lie alongside each other. In the terminal dendritic region, there are virtually no dendrites that do not end in apposition to a dendrite of a neighboring cholinergic amacrine cell. When small clusters of nearby cells were injected, an ordered microstructure appeared. The dendrites of the cells join together to form curving bundles, which enclose spaces that rarely contain any cholinergic dendrites: the appearance of the dendritic mosaic is that of a lattice with a repeating unit roughly 10 microns in diameter. The significance of this ordering is not certain, but it is possible that the repeating structural unit participates in a modular functional arrangement. PMID- 4032009 TI - The regional distribution and the chemical, chromatographic, and immunologic characterization of motilin brain peptides: the evidence for a difference between brain and intestinal motilin-immunoreactive peptides. AB - Motilin-like immunoreactive peptides (MLIPs) have been detected in the brain by radioimmunoassay (RIA), (Yanaihara, C., H. Sato, N. Yanaihara, S. Naruse, W. G. Forssman, V. Helmstaedter, T. Fujita, K. Yamaguchi, and K. Abe (1977) Adv. Exp. Biol. Med. 106: 269-283; Chey, W. Y., R. Escoffery, F. Roth, T. M. Chang, and H. Yajima (1980) Regul. Pept. Suppl. 1: 519; O'Donohue, T. L., M. C. Beinfeld, W. Y. Chey, T. M. Chang, G. Nilaver, E. A. Zimmerman, H. Yajima, H. Adachi, M. Roth, R. P. McDevitt, and D. M. Jacobowitz (1981) Peptides 2: 467-477). Previous studies (O'Donohue et al., 1981) demonstrated that MLIPs in rat brain probably differ chemically from porcine intestinal motilin (PIM), the first motilin peptide isolated. The possibility that this rat-pig difference represents a species difference was not examined in the previous study (O'Donohue et al., 1981), neither was the question of the cross-species distribution of MLIP. This study was initiated to examine brain MLIP distribution by RIA in three additional species: cow, pig, and guinea pig. The question of rat-pig species differences was addressed by characterizing MLIP in the brains of these species in comparison to PIM. By RIA, MLIPs were widely distributed in the brains of all species examined. MLIP concentration was highest in rat brain and lowest in pig brain. Some motilin antisera consistently detected less or no MLIPs in some brain regions of all species. Rat pituitary, pineal gland, and retina had substantially higher MLIP concentrations than did brain. MLIPs were abundant throughout the rat gastrointestinal tract and in some other peripheral organs.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4032010 TI - Two different mechanisms of calcium spike modulation by dopamine. AB - Dopamine (10 to 50 microM) modulates in two different ways the duration of the Ca2+-dependent action potential recorded in the cell body of identified neurons of the snail Helix aspersa. In some neurons (cells E13 and F1) dopamine increases the amplitude of their Ca2+-dependent spike plateau by decreasing the S-current (Klein, M., J.S. Camardo, and E. R. Kandel (1982) Proc. Natl. Acad. Sci. U.S.A. 79: 5713-5717), a K+ current controlled by cyclic AMP. In another neuron (cell D2), dopamine decreases the Ca2+-dependent plateau of the somatic action potential by evoking a decrease in Ca2+-current resulting from a decrease in Ca2+ conductance. Both modulatory effects could be observed in the same single neuron in which dopamine induces decreases of both the Ca2+ conductance and cyclic AMP dependent K+ conductance. Nevertheless, in these cells (such as cell F5) dopamine only evokes a decrease of the amplitude of the Ca2+ spike plateau. Since the modulation of the duration of the Ca2+ action potential recorded in the neuronal soma has been shown to constitute a good model of events taking place at synaptic endings, it is suggested that these modulatory mechanisms evoked by dopamine may be involved in processes of presynaptic facilitation and inhibition. PMID- 4032012 TI - Radical resection of intramedullary spinal cord tumors in adults. Recent experience in 29 patients. AB - The management of patients with intramedullary spinal cord tumors is controversial. In the past, these tumors have often been treated with biopsy or subtotal removal followed by irradiation--a therapy that is usually associated with early tumor recurrence and progressive neurological impairment. In an attempt to improve on the outcome of patients with intramedullary tumors, the authors performed radical resection in most of the 29 adult patients who had surgery for these tumors within the past 30 months. The mean duration of symptoms was 9 1/2 years, and all patients presented because of progressive neurological deficit. Patients were evaluated with metrizamide myelography-computerized tomography scanning and intraoperative ultrasound imaging to define the site of the tumor and cystic components. There were 14 ependymomas, 11 astrocytomas, two lipomas, and one case each of intramedullary fibrosis and astrogliosis. Solid tumor spanned a mean of five spinal cord segments and 16 tumors were associated with cysts. Twenty tumors were in the cervical and/or cervicothoracic regions. Total removal was achieved in 14 patients and "99% removal" in seven others. In 21 of 29 patients (72%), the neurological condition was stabilized or improved as a result of the operation. Postoperative deterioration occurred for the most part in patients who could not walk or who had minimal motor function at the time of operation, and these patients are no longer considered as operative candidates. Radical resection of intramedullary tumors can be achieved, with stabilization or improvement of neurological deficit in the majority of patients. PMID- 4032011 TI - Muscle denervation increases the levels of two mRNAs coding for the acetylcholine receptor alpha-subunit. AB - The mRNA coding for the alpha-subunit of the acetylcholine receptor was studied in mouse leg and rat diaphragm muscle. We find that denervation of rat diaphragm results in a 7-fold increase in mRNA coding for the alpha-subunit, whereas denervation of mouse leg muscle results in approximately a 50-fold increase in alpha-subunit-specific mRNA. The relationship of the mRNAs purified from innervated and denervated muscle was investigated by SI nuclease mapping. Two mRNA species were found in both innervated and denervated muscle which differ in their 3'-untranslated region. The levels of both these mRNA species increase upon denervation of mouse leg muscle. PMID- 4032013 TI - Odontoid upward migration in rheumatoid arthritis. An analysis of 45 patients with "cranial settling". AB - Lack of correlation between the severity of rheumatoid subluxation of the upper cervical vertebrae and supposed absence of neurological damage has led to the erroneous supposition that this finding is innocuous. Incomplete autopsy studies in rheumatoid arthritis have failed to recognize the cause of death, despite previously proven dramatic occipito-atlanto-axial dislocations. The most feared entity of rheumatoid basilar invagination, namely "cranial settling," is poorly understood. Between 1978 and 1984, the authors treated 45 rheumatoid arthritis patients who were symptomatic with "cranial settling." This consisted of vertical odontoid penetration through the foramen magnum (9 to 33 mm), occipito-atlanto axial dislocation, lateral atlantal mass erosion, downward telescoping of the anterior arch of C-1 on the axis, and rostral rotation of the posterior arch of C 1 producing ventral and dorsal cervicomedullary junction compromise. Cervicomedullary junction dysfunction has mistakenly been called "entrapment neuropathy," "progression of disease," or "vasculitis." Occipital pain occurred in all 45 patients, myelopathy in 36, blackout spells in 24, brain-stem signs in 17, and lower cranial nerve palsies in 10. Four patients had prior tracheostomies. Four previously asymptomatic patients with "cranial settling" presented acutely quadriplegic. The factors governing treatment were reducibility and direction of encroachment determined by skeletal traction and myelotomography. Transoral odontoidectomy was performed in seven patients with irreducible pathology. All patients underwent occipitocervical bone fusion (with C-1 decompression if needed) and acrylic fixation. Improvement occurred during traction, implying that compression might be the etiology for the neurological signs. There were no complications. Thus, "cranial settling" is a frequent complication of rheumatoid arthritis; although it is poorly recognized, it has serious implications and is treatable. PMID- 4032014 TI - Evaluation of acute nonpenetrating cervical spinal cord injuries with CT metrizamide myelography. AB - Computerized tomography metrizamide myelography was performed in 46 patients with acute, nonpenetrating cervical spinal cord injuries. By visualizing the spinal canal, spinal cord, and any compressive lesion, the study proved valuable in the decision as to whether surgical decompression was indicated and what approach should be used. Eleven patients were found to have significant spinal cord compression, 10 of whom were treated surgically. The technique, results, and complications resulting from the study are discussed. PMID- 4032015 TI - Results of extracranial-intracranial arterial bypass for bilateral carotid occlusion. AB - The results of superficial temporal to middle cerebral artery bypass surgery for bilateral internal carotid artery occlusion were reviewed in 39 patients. Preoperative symptoms included recurrent transient ischemic attacks (TIA's) in 31 patients (80%) and mild or moderate stroke in 15 (29%). Deficits were unilateral in 23 cases and bilateral in 14. Dementia or personality changes were observed in 19 patients (49%). Operative morbidity occurred in six of 39 cases and was neurological in one; the surgical mortality rate was 8% (three of 39 patients), including two cases of cerebral hemorrhage. The outcome was good or excellent (relief of TIA's and reduction of neurological deficit) in 82% of patients over a follow-up period of 3 to 139 months. Five patients had a late postoperative stroke, which occurred in the unoperated hemisphere in each case; one patient had an ipsilateral TIA 6 years after the bypass procedure. These results suggest that an extracranial-intracranial arterial bypass procedure to augment collateral cerebral blood flow can be performed safely in patients with bilateral internal carotid artery occlusion and may be associated with relief of ischemic symptoms. Future studies may document a role for this procedure in the prevention of stroke. PMID- 4032016 TI - Skull metastasis of thyroid carcinoma. Study of 12 cases. AB - Over the past 33 years the authors have treated 12 cases of skull metastasis from thyroid carcinoma, accounting for 2.5% of a total of 473 cases of thyroid cancer. A study of these 12 cases revealed the following characteristics. The mean age of the patients was 60.4 years and the predominant incidence was in the seventh decade of life. The incidence of skull metastasis from thyroid cancer was higher among women than among men. The primary sign was a soft hemispheric tumor resting on the skull. The tumors were rich in vascularity with osteolytic changes in the skull. The average period from diagnosis of the thyroid tumor until thyroidectomy was 14.3 years, and until discovery of the skull metastasis was 23.3 years. The clinical course was thus very long. The most frequent histopathological presentation was follicular adenocarcinoma. Such lesions were morphologically well differentiated, with little pleomorphism and atypism, but detailed examination showed infiltration into the vascular lumen or capsule. The mean survival time in these patients was 4.5 years from the time of diagnosis. The prognosis in this lesion was relatively poor, considering its long clinical course. PMID- 4032017 TI - Pneumocephalus in patients with CSF shunts. AB - The authors present two cases of pneumocephalus occurring in patients with permanent shunts and review nine previously reported cases. Mental status changes and headache are the most common presenting symptoms. Six of the 11 cases of pneumocephalus occurred in patients with shunt placement for hydrocephalus secondary to aqueductal stenosis. In these patients, thinned cerebrospinal fluid barriers secondary to long-standing increased intracranial pressure may predispose them to pneumocephalus. Temporary extraventricular drainage is an effective method of treatment in this group of patients. Two other etiologies are identified with significance to treatment, and the role of craniotomy is discussed. PMID- 4032018 TI - Survival times and case fatality rates of brain-injured persons. AB - Survival time after injury (the time from injury to death) imposes an important constraint on the timing of the delivery of postinjury medical care. From a population-based study of brain-injured people, the survival times in 542 cases with fatal outcomes were studied. Prehospital deaths as well as hospital deaths were included. Survival times were considerably shorter for 95 people with untreatable injuries (Abbreviated Injury Scale level 6) than for the remaining 447 whose injuries were potentially treatable. For the former group, the median survival time was 10 minutes; for the latter, it was 2 hours. For those with potentially treatable injuries, the median time from injury to receiving medical assistance was approximately 30 minutes and 82% received medical assistance within 1 hour of injury. Short survival time was associated with prehospital death, young age, high Injury Severity Score, and having a nonbrain injury as the most severe injury. For patients who arrived alive at a hospital, intracranial surgery was associated with increased survival time. PMID- 4032019 TI - Somatosensory evoked potentials evaluated in normal subjects and spinal cord injured patients. AB - Somatosensory evoked cortical potentials (SSEP's) were recorded in 27 healthy subjects using tibial and peroneal nerve stimulation with cephalic and non cephalic references. Four major peaks were present in all recordings. Analysis of these components showed that SSEP's collected after tibial nerve stimulation with non-cephalic reference (linked earlobes) produced the most consistent clearly defined component peaks. Average latency, amplitude, and interpeak latency differences are presented for these SSEP's. Significant correlations were obtained between the height of the individual and the P1, N2, P2, and N3 latencies, and the N3-P1 interpeak latency. These results suggest that reproducible SSEP's can be obtained from tibial nerve stimulation in normal subjects using minimal numbers of stimulus presentations (28 to 64). The SSEP's from 34 patients with varying degrees of spinal cord trauma were compared with the SSEP's from normal subjects. These comparisons involved the P1, N2, P2, and N3 latencies and the interpeak latency values, as well as the amplitude values. Patients with normal sensory and motor neurological examinations could be distinguished from patients showing decreased sensory and motor findings or clinically complete lesions on the basis of peak latency and interpeak latency values. The latter two groups could not be distinguished from one another. In general, all patient groups had SSEP's of lower amplitude than did normal individuals, but the groups could not be distinguished from one another. These results indicate that SSEP's can be a useful clinical tool for differentiation of complete from incomplete spinal cord lesions, but do not invariably predict recovery of function. PMID- 4032020 TI - Brain blood volume and blood flow in patients with plateau waves. AB - Plateau waves, characterized by acute transient rises of the intracranial pressure (ICP), are accompanied by a marked decrease of the cerebral perfusion pressure. Patients with plateau waves, however, often show no clinical symptoms of ischemia of the brain stem, such as vasopressor response or impairment of consciousness during the waves. The authors studied brain blood volume and blood flow with dynamic computerized tomography using rapid-sequence scanning in patients with plateau waves identified during continuous ICP recording. Following an intravenous bolus injection of contrast medium, density-versus-time curves were obtained for the regions of interest; that is, the frontal lobe, the temporal lobe, the caudate nucleus, the putamen, and the pons. The dynamic studies were undertaken when the ICP was high during a plateau-wave phase and when it was low during an interval phase between two plateau waves. The results indicate that, in the cerebral hemisphere (frontal lobe, temporal lobe, caudate nucleus, and putamen), plateau waves were accompanied by an increase in blood volume and, at the same time, a decrease in blood flow. In the pons, however, both the blood volume and blood flow showed little change during plateau waves as compared with the intervals between two plateau waves. These observations may explain why there is no rise in the systemic blood pressure and why patients are often alert during plateau waves. PMID- 4032021 TI - Thymidine kinase in brain-tumor cysts. AB - A recently developed method for deoxythymidine kinase (TK) determination was applied to brain-tumor cyst fluid and fluid from a non-neoplastic intracerebral cyst. The fluid from all tumors tested positive for TK whereas the non-neoplastic cyst lacked TK. Cyst fluid was also analyzed for TK before and after intracystic instillation of BCNU. It is suggested that TK activity in the fluid in cystic brain lesions could prove useful in deciding whether an intracerebral lesion is neoplastic. Also, TK activity can be used to evaluate the effect of topical therapy. PMID- 4032022 TI - Clinical evaluation of two methods of subdural pressure monitoring. AB - Recordings from two different types of subdural pressure monitor with simultaneous intraventricular pressure (IVP) tracings are compared in 20 head injured patients. In the first 10 patients a fluid-filled catheter was placed subdurally and connected to an external transducer, and in the second 10 the Gaeltec model ICT/b solid state miniature transducer was used. The latter system has the advantage that both zero and calibration checks can be carried out after insertion. Only 44% of the fluid-filled catheter readings corresponded with IVP in series of 10-mm Hg ranges, while 53% of readings were lower; this tendency was more marked at higher pressures. With the Gaeltec transducer, 72% of subdural pressure readings corresponded with IVP, while only 9% were lower and 19% were higher than IVP. The differences may have been due to technical causes or to true pressure differentials. The subdural catheter appears too unreliable for routine clinical use, but the Gaeltec transducer may be a satisfactory alternative to ventricular pressure monitoring. PMID- 4032023 TI - Nimodipine levels in gerbil brain following parenteral drug administration. AB - Nimodipine binding to the particulate fraction of gerbil brain homogenate was characterized using tritiated (3H)-nimodipine as the radioactive ligand. Binding was monophasic and saturable, with the apparent affinity constant (KD) = 0.4 nM and the maximum number of binding sites (Bmax) = 12 nmol/kg wet wt. A competitive binding assay was validated for the measurement of nimodipine using gerbil brain as the source of receptors for the drug. Binding characteristics were sufficiently similar in specimens from different animals to allow the use of homogenates from individual animals as the source of both membrane-binding sites and competing ligand. Nimodipine could be detected in the brains of animals sacrificed soon after drug injection, and reached a peak level within 15 minutes. Brain drug level at a given time was a linear function of dose administered. One hour after a 1-mg/kg dose, the level of drug measured in brain was approximately 100 nmol/kg wet wt, more that 200 times the KD. Sufficient drug to mediate a maximal pharmacological effect accumulated in brain even after a dose of only 0.25 mg/kg. Thus, in this species, effective tissue nimodipine levels may be achieved at doses which minimize the risk of systemic hypotension. PMID- 4032024 TI - Choroid plexus as a barrier to immunoglobulin delivery into cerebrospinal fluid. AB - The concentration of gamma globulins is greatly increased in the cerebrospinal fluid (CSF) during inflammatory and degenerative disorders of the central nervous system (CNS). The mechanism by which immunoglobulins enter the CSF under normal conditions is unknown. The extent of participation of the blood-brain barrier in protein delivery to the CSF is unclear, although the choroid plexus is known to have primary responsibility for the formation and movement of certain proteins into the CSF. To investigate the role of the choroid plexus in immunoglobulin delivery to the CSF, the authors evaluated rat brain tissue by light and electron microscopic immunohistochemical technique using the peroxidase technique of immunoglobulin (Ig)G and IgA detection. Peanut agglutinin was used to identify macrophages, cells known to have important immune functions and which have been reported as a normal component of the choroid plexus. Antisera to IgG' and IgA demonstrated diffuse surface staining of the choroidal epithelial cells with light and electron microscopy; the cytoplasm and nuclei did not contain immunoglobulins. Macrophages were not present in the choroid plexus, in contrast to previous reports. The results demonstrate that immunoglobulins do not enter the CSF via the choroid plexus, unlike other proteins in similar concentrations in the CSF. In addition, macrophages are shown to be an insignificant component of the plexus, thereby further diminishing the likelihood of participation-of the choroid plexus in the regulation of immunoglobulin entry into the CNS under normal conditions. PMID- 4032025 TI - The risk of cerebral damage during graded brain retractor pressure in the rat. AB - A considerable reduction in regional cerebral blood flow has been demonstrated with brain retraction at a pressure of 30 mm Hg. The authors undertook a neuropathological study to assess the effect on brain tissue of brain retractors applied at varying pressures for 15 minutes. The following changes were found: after 20 mm Hg of brain retractor pressure (BRP) only one of six brains revealed infarction involving all cortical layers; after 30 mm Hg of BRP cortical infarction, partly hemorrhagic, was found in five of six brains; after 40 mm Hg of BRP all six animals showed cortical damage. There were no signs of cerebral damage outside the retractor application area or in deeper brain structures. It was concluded that only if BRP did not exceed 20 mm Hg for 15 minutes could damage be avoided in this model. PMID- 4032026 TI - Regional brain metabolite levels following mild experimental head injury in the cat. AB - Glucose, adenosine triphosphate, phosphocreatine, and lactate levels in the cortex, striatum, diencephalon, hippocampus, cerebellum, and brain stem were measured in cats 1 hour after they were subjected to low-level (2 atm) fluid percussion injury. Following injury, there was a mild but significant increase in lactate levels in the majority of regions studied. The hippocampus exhibited the highest percentage increase in lactate (fourfold). The cortical area directly under the trauma device showed a threefold lactate increase, while there was a twofold increase in other brain regions studied. Although there were consistent decreases in phosphocreatine levels, these decreases were significant only in the hippocampus (p less than 0.05). Glucose levels in all brain regions studied were no different from control levels at the time of study. The unchanged glucose levels, together with previous studies of identically injured cats showing that cerebral blood flow was unimpaired, suggest that excess lactate was not a consequence of cerebral ischemia. Rather, the increase in lactate levels may indicate that concussive injury can produce a mild derangement of brain energy metabolism in the absence of substrate limitations. This derangement may reflect altered mitochondrial function. PMID- 4032027 TI - Occipital artery to extradural vertebral artery bypass procedure. Case report. AB - A 17-year-old boy suffered blunt trauma to the posterior cervical spine and later developed vertebrobasilar transient ischemic attacks refractory to medical management. At angiography, a pseudoaneurysm of the distal left vertebral artery was found. By means of a posterior midline approach, an extradural occipital artery to vertebral artery anastomosis was performed and the affected vertebral artery was clipped distal to the pseudoaneurysm. The indications for this procedure, the operative approach, and the clinical outcome are described. PMID- 4032028 TI - Accessory nerve palsy following carotid endarterectomy. Report of two cases. AB - Two patients who had an accessory nerve palsy following carotid endarterectomy are presented. Both patients had high carotid bifurcations necessitating unusually high retraction and dissection. The ipsilateral accessory nerve was injured in the anterior cervical triangle in both cases. It is believed that vigorous lateral retraction of the superior aspect of the sternocleidomastoid muscle led to a stretch injury of the nerve. The symptoms completely resolved in both patients within 6 months. PMID- 4032029 TI - Symptomatic root compression by a free fat transplant after hemilaminectomy. Case report. AB - The authors report a case in which a free fat graft, placed at the operative site after hemilaminectomy for lumbar disc herniation, was forced into the spinal canal by action of the paraspinal muscles and behaved as a symptomatic space occupying lesion. The patient recovered satisfactorily after the graft was removed. The pathogenetic mechanism is discussed and guidelines to avoid this complication are outlined. PMID- 4032030 TI - Chronic spinal subdural hematomas. Report of two cases. AB - Two patients with chronic spinal subdural hematomas are described. Both had a fluctuating clinical course, not previously documented in the literature. Surgical evacuation resulted in almost complete recovery. The pathogenesis of spinal subdural hematoma is discussed and the pertinent literature is reviewed. PMID- 4032031 TI - Temporary bypass for AVM surgery. PMID- 4032032 TI - Cognitive impairment after early aneurysm surgery. PMID- 4032033 TI - Medical consequences of nuclear weapons today: "final epidemic"? PMID- 4032034 TI - Gold-195m: a steady-state imaging agent for venography that gives blood velocity measurement. AB - Gold-195m has found applications in first-pass studies for investigating both right and left ventricular activity as well as lung transit. Owing to its reasonably short half-life of 30 sec we have found it particularly useful for imaging leg veins up to and including the inferior vena cava. Its short half-life prevents recirculation activity from appearing, so continuous perfusion into a superficial foot vein and application of ankle tourniquets yield a steady-state image of the deep veins, with particularly good resolution. Its decay pattern along a vessel is very sensitive to blood velocity, so measurement of activity at various points on a vein in a computer static image can give velocity values that reveal abnormalities due to partial or complete thrombosis. The radiation dosimetry of 195mAu used in this way is lower than contrast and technetium-99m macroaggregated albumin [( 99mTc]MAA) venography, making it particularly useful for investigating deep vein thrombosis (DVT) in pregnancy. PMID- 4032035 TI - Radionuclide hysterosalpingography for evaluation of fallopian tube patency. AB - A prospective study was undertaken to evaluate the efficacy of radionuclide hysterosalpingography (RNHSG) using a technique with some modifications, that was described by Iturralde and Ventner (1). As these investigators demonstrated, technetium-labeled human albumin microspheres (HAM) will normally migrate spontaneously from the vagina to the ovaries. This study confirms that in the presence of fallopian tube obstruction, fibrosis and/or lack of motility, this migration does not take place, and that the presence or absence of migration of HAM can be imaged with a gamma camera. In the evaluation of 52 tubes we found that the efficiency of RNHSG for evaluation of fallopian tube patency when compared with contrast hysterosalpingography and/or direct observation of surgical pathology was over 94%. RNHSG is an essentially innocuous technique for assessing functional and mechanical fallopian tube obstruction that can be performed with conventional nuclear imaging equipment. PMID- 4032036 TI - Effect of a delay in commencing imaging on the ability to detect transient thallium defects. AB - Sixty patients, 42 with coronary disease and 18 normals, were studied to assess the impact of a delay following exercise in commencing thallium imaging on the sensitivity for detecting ischemic transient defects. Three sets of images were obtained beginning 2 min, 18 min, and 2 hr after exercise. Each patient's images were separated into two pairs of studies for analysis: 2 min-2 hr and 18 min-2 hr. Of the 42 patients with coronary disease, a greater number had transient defects detected on the 2 min-2 hr compared with the 18 min-2 hr study (22 compared with 14, p less than 0.05). False positives were not increased by earlier imaging. We conclude that a modest (18 min) delay obtaining the first set of images causes a significant reduction in the ability to detect transient thallium defects, and that imaging should begin several minutes after exercise. PMID- 4032037 TI - A simple method to quantitate iodine-124 contamination in iodine-123 radiopharmaceuticals. AB - Iodine-123 (123I) produced by the 124Te(p,2n)123I reaction contains several percent 124I radionuclidic contamination at the time of imaging. Since 124I degrades the quality of the images and causes unnecessary radiation absorbed dose to the patient, it is important to know the amount present in radiopharmaceuticals at the time of administration. A simple approach is described which uses a radionuclide dose calibrator and lead shield. The sample is assayed both shielded and unshielded and the ratio of readings depends uniquely upon the percent 124I present. The technique can be adopted for any type of dose calibrator, sample container, and Pb shield, but use of the numeric constants reported here should be restricted to the specified equipment. PMID- 4032038 TI - The relationship of nuclear magnetic resonance to nuclear medicine: friend or foe? PMID- 4032039 TI - Enterogastric reflux mimicking gallbladder visualization in acute cholecystitis. PMID- 4032041 TI - Imaging in patients with heterotopic bone formation. PMID- 4032040 TI - Depletion regimens for radioiodine therapy of thyroid carcinoma. PMID- 4032042 TI - Receiver operating characteristic analysis of regional cerebral blood flow in Alzheimer's disease. AB - Receiver operating characteristic (ROC) curves were used to quantitatively assess the ability of individual detectors in a 32-detector 133Xe inhalation system to discriminate between two populations over the range of regional cerebral blood flow (rCBF) values. These populations were clinically evaluated as normal (age 63.1 +/- 13.1, n = 23) and presumed Alzheimer's disease (age 72.7 +/- 7.0, n = 82). Summary statistics showed that for homologous detectors the average value of blood flow in the normal group was greater than the flow value in the group of subjects with Alzheimer's disease. Conclusions drawn from single values of flow or mean hemispheric flow can lead to erroneous conclusions about hemisphere asymmetries. However, the dynamic relationship between the correct identifications (true positives) compared with incorrect identifications (false positives) of Alzheimer's disease at each detector varies over the range of blood flow values, and quantitative characterization of this relationship in terms of an ROC curve provides more insight into the structure of the data. Detectors approximating the speech, auditory and association cortex were most effective in discriminating between groups. Frontal detectors were marginally useful diagnostically. PMID- 4032043 TI - Unsuccessful lung scan due to major right-to-left shunt through a sinus venosus septal defect. AB - In a patient with a prior history of cerebral abscess and cerebral ischemia, an unsuccessful perfusion lung scan led to a radionuclide angiocardiogram using an arm vein injection. This showed a total right-to-left (R-L) shunt from the superior vena cava (SVC) to the left atrium. Repeat radionuclide study, through a leg vein, demonstrated a moderate R-L shunt and an interpretable lung scan could be obtained. Catheterization and contrast cineangiogram did not provide the exact diagnosis, the preoperative conclusion being anomalous drainage of the SVC into the left atrium, with atrial septal defect (ASD) and partial anomalous pulmonary venous connection to the SVC. The operative diagnosis was high atrial (sinus venosus) septal defect. This example of major but clinically unsuspected R-L shunt emphasizes the value of performing a perfusion lung scan, preferably in conjunction with radionuclide angiocardiography in patients with a prior history of unexplained cerebral abscess or systemic ischemia. Implications of the site of an ASD on quantitation of L-R shunts by radionuclide methods are also discussed. PMID- 4032044 TI - Radionuclide angiography in pulmonary sequestration. AB - We report a case diagnosed as pulmonary sequestration by radionuclide angiography prior to operation which showed anomalous arteries. Radionuclide angiography clearly revealed the condition of both the pulmonary artery and aorta, and is considered to be extremely useful in the diagnosis of pulmonary sequestration. It will probably be applied to more patients in the future. PMID- 4032045 TI - Hemoptysis as the sole presentation of thyroid carcinoma. AB - A 23-year-old man experienced hemoptysis in 1968, secondary to papillary carcinoma of the thyroid with metastasis to the lungs. The patient was treated initially with thyroidectomy and Iodine- 131 (131I), and subsequently with radical neck dissection. Following a period of fifteen years in which the patient was well clinically, he experienced recurrent hemoptysis. No other source of bleeding was identified, and the hemoptysis was attributed to the lung metastases of the thyroid carcinoma. PMID- 4032046 TI - Technetium-99m low density lipoproteins: preparation and biodistribution. AB - The focal uptake by human atherosclerotic lesions of 125I bound to low density lipoproteins (LDL) can be demonstrated by external imaging. However, 125I has poor imaging characteristics. Therefore, we have developed a technique for labeling LDL with technetium. To facilitate analysis, LDL was first labeled with 99mTc, by reduction of TcO4- with dithionite in the presence of the protein. The labeled LDL was stable to electrophoresis, ultracentrifugation, and passage in vivo. This technique was repeated with minor modification with 99mTc to prepare [99mTc] LDL for use as an imaging agent. Its biodistribution in 16 rabbits was similar to that of [125I] LDL and it allowed high resolution external imaging of LDL uptake by tissues, including the injured, healing, arterial wall, and the adrenal cortex. PMID- 4032047 TI - Radiation dosimetry of radioiodinated thyroid hormones. AB - A physiologically based compartmental model for T4 and T3 metabolism in man was used to generate time-activity curves for residence of radioiodine in key organs. T4 and T3 labeled with 123I, 124I, 125I, and 131I were studied. Conditions modeled included radioactive iodine uptake (RAIU) values of 0%, 1%, 5%, 15% and 25%, and RAIU of 15% combined with various degrees of pharmacologic block of thyroidal RAIU. Using the MIRD "S" tables, rad doses were generated for each condition. While the shapes of the time-activity curves varied widely with alterations in physical and biological turnover and with changes in steady-state due to iodine administration, it was possible to calculate overall effective half lives for each organ of interest from the integral of the time-activity curve projected by solution of the model. This overall effective half-life of the hormone for the body's exchangeable hormone compartments correlated well with calculated radiation dose to the thyroid in the unblocked state. With progressive degrees of iodine block, this correlation persisted, though with proportionately reduced thyroid radiation doses. Use and manipulation of a compartmental model, rather than the usual multiexponential model, for radiation dosimetry facilitates conceptualization and the projection of the effects of interventions such as iodide block. PMID- 4032048 TI - A simple filtering routine for radionuclide bone images. AB - The evaluation is carried out of a simple filtering routine for improving the detectability of low contrast lesions in bone scans. With this routine, the unprocessed image is displayed together with three filtered versions, the final decision on the presence of abnormalities being made by comparing the four images. Emphasis is placed on producing a routine which is quick in implementation and, therefore, only small filter arrays are used. Using a routine consisting of a low-pass, a median, and a differential filter, 73% more lesions are detected when the filtered images are also used. The whole routine takes less than 1 min to run. PMID- 4032049 TI - Excretion of radionuclides in human breast milk after the administration of radiopharmaceuticals. AB - The fraction of injected activity that was excreted through the breast milk of nursing mothers at different times after the injection of various radiopharmaceuticals has been measured in 21 patients. For 99mTc-labeled radiopharmaceuticals the total excreted fraction was 10% for pertechnetate and 1.5-3% for MAA, plasmin, diethylenetriaminepentaacetic acid (DTPA), and methylene diphosphonate (MDP). For [125I]hippuran and [131I]hippuran the corresponding value was 3%. For the above mentioned radiopharmaceuticals the activity concentration in the milk decreased exponentially with an effective half-life of approximately 4 hr. For chromium-51 ethylenediaminetetraacetic acid ([51Cr]EDTA) and [99mTc]RBC, much smaller amounts were excreted in the breast milk. The absorbed dose to various organs of the baby has been calculated. We conclude that when [99mTc]pertechnetate, [99mTc]MAA, [99mTc]plasmin, [125I]hippuran, or [131I]hippuran are used the child should be fed just before the administration of the radionuclide to the mother and the next three milk fractions should not be used. For [99mTc]DTPA and [99mTc]MDP as well as [51Cr]EDTA, only the first fraction should not be used. According to our earlier investigations breast feeding has to be stopped for at least 3 wk after investigations with [125I]fibrinogen. PMID- 4032050 TI - Excretion of radioactivity in breast milk after an indium-111 leukocyte scan. PMID- 4032051 TI - Thyroid carcinoma metastatic to pituitary. PMID- 4032052 TI - Use of a cardiac phantom for intersystem survey. PMID- 4032053 TI - Schilling evaluation of pernicious anemia. PMID- 4032054 TI - Misplaced hydroxyl group in figure: the synthesis of 2-[F-18] fluoro-2-deoxy-D glucose using glycals. PMID- 4032055 TI - Effect of soft-tissue pathology on detection of pedal osteomyelitis in diabetics. AB - Three-phase bone scans were performed on 30 diabetic patients suspected of having acute pedal osteomyelitis; 23 also had a pedal ulcer, seven had coexisting cellulitis, and 14 had diminished pedal pulses. Fifteen patients were receiving antibiotics at the time of the scan. A tissue diagnosis was available in 18 patients and 12 had no clinical evidence of infection on follow-up. Focal arterial hyperemia combined with focally increased activity on blood-pool and delayed (2-3 hr) scans were interpreted as acute osteomyelitis. Scans showing venous hyperemia were interpreted as soft-tissue pathology without acute osteomyelitis. Companion radiographs were reviewed independently. The sensitivity and specificity of the scans for osteomyelitis were 0.94 and 0.79, respectively, while radiographic sensitivity was 0.93 and specificity was 0.50. The presence of soft-tissue ulcers or cellulitis, peripheral vascular disease, or recent antibiotic therapy had no significant adverse effect on the accuracy of the three phase scan in diagnosing osteomyelitis. PMID- 4032056 TI - First-third ejection fraction: is the first-pass radionuclide method accurate? AB - Previous reports have suggested that left ventricular first-third ejection fraction (EF) can be obtained from the left ventricular time-activity curve derived from first-pass radionuclide angiography based on Anger camera data. The validity of this technique was assessed by: a study of beat-to-beat variations in data from 15 patients in which electrocardiographic data were simultaneously recorded, and a computer simulation incorporating the application of Poisson statistics to appropriate count rate data. The results of patients studies showed no consistent trend in any first-third parameter obtained from consecutive beats in individual subjects, and unacceptably high statistical uncertainty in the calculation of the first-third ejection fraction. The weighted standard deviation of the first-third ejection fraction in each of 15 patients studied averaged 7.5 EF units, while first-third ejection fraction averaged 22.9 EF units. The relative error averaged 32%. The computer simulation indicated a high relative error of 47% associated with the first-third ejection fraction at typical end diastolic count rates of 200 per frame from 1,000 computer Poisson randomizations of an appropriate analog volume curve. The results render the first-pass radiocardiographic method invalid for determining first-third ejection fraction. PMID- 4032058 TI - The XXI National Congress of the Italian Society for Nuclear Biology and Medicine held in association with the VII annual meeting of the Nuclear Medicine Section of the Italian Association for Radiology and Nuclear Medicine. Genoa, Italy, May 29-June 1, 1985. Abstracts of the communications. PMID- 4032057 TI - Do radioisotope techniques fulfil their role in the diagnosis of pulmonary embolism? PMID- 4032059 TI - Evaluation of the erythrocyte aspartate aminotransferase activity coefficient as an indicator of the vitamin B-6 status of postpubertal gilts. AB - In two experiments, postpubertal gilts, individually housed in gestation stalls, were fed daily 1.9 kg of a purified diet providing 0.45, 1.5, 2.1 or 83 mg of vitamin B-6/d. The erythrocyte aspartate aminotransferase (more commonly known as glutamic-oxaloacetic transaminase) activity coefficient (EGOT-Ac) of gilts fed the low vitamin B-6 diet (0.45 mg vitamin B-6/d) for 121 d increased 200%, while the EGOT-Ac of gilts fed the high vitamin B-6 diet (83 mg vitamin B-6/d) remained unchanged. Two gilts were fed the low vitamin B-6 diet for 241 d at which time hair loss was observed. Muscle glutamic-oxaloacetic transaminase activity was reduced 75% in vitamin B-6-deficient gilts. The EGOT-Ac of gilts consuming 2.1 mg vitamin B-6/d was 100% greater than that of control animals (83 mg vitamin B 6/d). These findings indicate that the current NRC estimated vitamin B-6 requirement for mature swine (1.8 mg vitamin B-6/d) is inadequate. Prior intake of excess vitamin B-6 did not prevent the subsequent development of a vitamin B-6 deficiency. PMID- 4032060 TI - Effect of deficient and excess dietary vitamin B-6 on amino transaminase and glycogen phosphorylase activity and pyridoxal phosphate content in two muscles from postpubertal gilts. AB - Postpubertal gilts averaging 111 kg and gaining 2.7 kg/wk were fed daily 1.9 kg/d of a diet providing 0.45, 2.1 or 83 mg of vitamin B-6/d. An additional group of animals were fed the high vitamin B-6 diet providing 83 mg of vitamin B-6/d for the initial 57 d of the experiment and then switched to 0.45 mg of vitamin B-6/d for the remainder of the 121-d experiment (61 gilts total). On d 0, 57 and 121, animals from each treatment were killed, and samples of the semitendinosus (ST) and semimembranosus (SM) were removed. Glutamic-oxaloacetic transaminase (GOT), glutamic-pyruvic transaminase (GPT), glycogen phosphorylase and pyridoxal phosphate (PLP) were measured in muscle tissues. The erythrocyte GOT activity coefficient indicated that gilts consuming 0.45 or 2.1 mg of vitamin B-6/d developed a vitamin B-6 deficiency. A vitamin B-6 deficiency resulted in the loss of whole-muscle transaminase activity (enzyme activity X muscle weight) with little effect on whole-muscle total phosphorylase or total PLP content. Excess dietary vitamin B-6 increased whole-muscle total PLP and total phosphorylase content with small decreases in whole-muscle transaminase. Under these conditions, muscle tissue acts as a nonmobile reservoir of PLP. Sixty to 95% of muscle PLP was bound to muscle glycogen phosphorylase. PMID- 4032061 TI - A comparison of the response of woodchucks and rats to variations in dietary lipotrope and lipid content. AB - A soy protein-based experimental diet for woodchucks (Marmota monax) is described. The diet supported growth of juvenile woodchucks for 12 wk. With this diet, the effects on both woodchucks and rats of increasing dietary corn oil from 5 to 15% and of deleting supplemental lipotropic factors (choline, methionine, folic acid and vitamin B-12) were studied in a 2 X 2 factorial experiment. Both increased lipid and lipotrope deletion resulted in decreased growth in rats, but only increased lipid caused growth depression in woodchucks. Lipotrope depletion resulted in elevated serum markers of hepatic injury and hepatic lipid accumulation in rats but not in woodchucks. Hematological changes induced by the low lipotrope diets included decreased packed cell volume, total hemoglobin and mean corpuscular volume (MCV) in rats but increased MCV in woodchucks. The woodchuck appears to be more resistant than the rat to induction of hepatic injury by lipotrope deficiency. PMID- 4032062 TI - Dietary induction of hypercholesterolemia and atherosclerosis in Japanese quail of strain SEA. AB - Groups of 12 male Japanese quail (Coturnix coturnix japonica) of a strain susceptible to experimental atherosclerosis (SEA) were fed one of three purified diets (one basal and two atherogenic) for 8 wk. The basal diet contained: glucose (46%), soy protein (35%) and beef tallow (10%). Atherogenic diets were prepared by replacing glucose with either 1% cholesterol or 1% cholesterol plus 0.5% cholic acid. Both atherogenic diets induced hypercholesterolemia, with serum cholesterol increased 202 and 336% above basal values for birds fed the cholesterol and cholesterol/cholic acid diets, respectively. The hypercholesterolemia was characterized by an increase in serum levels of very low density and low density lipoprotein cholesterol. No atherosclerotic lesions were found in birds fed the basal diet, but lesion incidence in the dorsal aorta and brachiocephalic arteries was 75 and 100% for birds fed the cholesterol and cholesterol/cholic acid diets, respectively. Arterial scores (percentage of arterial surface area covered by lesions), arterial cholesterol concentration and total liver cholesterol were significantly higher (P less than 0.05) for birds fed the cholic acid containing diet than for those fed the diet having cholesterol only. Severity of atherosclerotic score and arterial cholesterol concentration were positively correlated (P less than 0.01 in both cases) with serum cholesterol concentration. The two indices of the severity of atherosclerosis (arterial score and arterial cholesterol concentration) were highly and linearly correlated (r = 0.88, P less than 0.01). The SEA strain of quail appears to be a promising model for the study of atherosclerosis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4032063 TI - Influence of zinc and iron on dietary fluoride utilization in the rat. AB - Two experiments were conducted with the weanling rat fed a purified diet to determine the influence of dietary zinc (6, 30, 150 ppm) and iron (7, 35, 175 ppm) on fluoride bioavailability. Dietary fluoride in each case was 2 or 10 ppm as sodium fluoride. During a 6-wk trial, neither divalent zinc nor divalent iron affected fluoride bioavailability based on skeletal uptake of fluoride. Our studies were specifically designed to provide concepts about the effects of dietary trace element supplementation practices on dietary fluoride bioavailability especially in terms of fluoride originating from foods prepared in fluoridated water. Our results suggest that either iron or zinc can be added to foods to improve nutritional value without compromising the availability of food fluoride. PMID- 4032064 TI - Effect of lactose on phosphate transport into rat intestinal brush border membrane vesicles. AB - Brush border membrane vesicles (BBMV) were used to evaluate the influence of lactose on phosphate (Pi) transport in the intestine of the rat. BBMV were prepared from duodenum, jejunum and ileum of 3-, 4- and 7-wk-old rats. Na+ dependent active transport of Pi was investigated in the presence of an Na+ gradient; Na+-independent, diffusional transport was investigated by substitution of choline chloride for NaCl. In 3-wk-old rats active Pi transport dominated, whereas in 4-wk-old rats a decrease in active transport and an increase of the diffusional component of total Pi transport were observed. Furthermore, in 7-wk old rats, Pi was transported by simple diffusion alone. Addition of lactose to the preincubation medium had no effect on Pi transport in duodenal and jejunal BBMV isolated from 3-wk-old rats. In the remaining BBMV preparations, lactose caused a twofold enhancement of diffusional Pi uptake. Glucose and galactose had no effect on diffusional Pi uptake into BBMV. These results indicate that lactose may directly interact with luminal membranes, thus leading to increased diffusional transport. The membranes with a decreased Na+-dependent Pi transport activity are most susceptible to the influence of lactose. PMID- 4032065 TI - Isolation and characterization of brush border membrane vesicles from bovine small intestine. AB - Intestinal brush border membrane vesicles were prepared from 21-wk-old Holstein bulls. The method of preparation included magnesium precipitation, differential centrifugation and sucrose density gradient centrifugation. Purification of brush border membranes was indicated by sevenfold enrichment of alkaline phosphatase activity. Uptake of D-[U-14C]glucose was sodium-stimulated and exhibited characteristic "overshoot" phenomenon. Sodium-dependent and sodium-independent D glucose uptake was into an osmotically active space. Phloridzin (100 mM) completely inhibited sodium-dependent, but did not affect sodium-independent transport. Sodium-dependent D-glucose transport was inhibited more by D-glucose than by D-galactose, which inhibited more than D-xylose did. The sodium-dependent D-glucose transport was not inhibited by D-fructose, D-ribose or D-arabinose. Sodium-independent D-glucose transport was unaffected by the sugars tested. Glucose transport in bovine intestinal brush border is similar to that in monogastric species and is composed of two pathways: a sodium-dependent inhibitable system and a diffusional system. PMID- 4032066 TI - Food intake, growth and tissue amino acids in rats fed acid analogues. AB - The objective of this study was to examine the effects of dietary additions of analogues of large neutral amino acids (LNAA), previously shown to inhibit entry of natural LNAA into brain, on food intake, growth and tissue concentrations of specific amino acids in young rats. A mixture of norleucine, norvaline, alpha aminophenylacetate and alpha-aminooctanote (atypical amino acids, AAA) markedly depressed food intake and growth of rats fed a 6% protein diet (LP) for 10 d but not of rats fed a 50% protein diet (HP). Except in rats fed HP, dietary AAA usually decreased concentrations of LNAA more than of small neutral amino acids (SNAA) or lysine, especially in brain. Concentrations of LNAA, especially in brain and muscle of rats adapted to LP or HP meals and fed one LP-AAA meal were lower than in similar rats fed one LP meal without AAA; feeding an HP-AAA meal to such rats generally prevented or lessened these changes. AAA-induced changes in SNAA and lysine were usually small in meal-fed rats. When AAA induced decreases in LNAA, the branched-chain amino acids were usually most affected; valine and isoleucine sometimes were undetected in brain and muscle. Serotonin and dopamine concentrations were not low in brain despite low levels of tryptophan and tyrosine. Changes in tissue LNAA concentrations would appear to reflect in part competition by large neutral AAA for transport of natural LNAA from the blood. PMID- 4032067 TI - Effect of dietary selenium deficiency on incidence and size of 1,2 dimethylhydrazine-induced colon tumors in rats. AB - Torula yeast diets deficient (less than or equal to 0.02 ppm) in selenium (Se) and a control diet supplemented with sodium selenite (0.1 ppm Se), were fed to 52 male Sprague-Dawley rats per diet for 23 wk following weaning. 1,2 dimethylhydrazine (DMH) was administered (20 mg/kg body weight) in 20 weekly i.p. injections after 3 wk of feeding. After 23 wk, 67% of the rats fed the Se deficient diet had intestinal adenocarcinomas versus 63% on the 0.1 ppm Se diets. Diet also had no effect on the number or size of tumors per tumor-bearing animal or on the location of the tumors within the colon. The effects of Se deficiency on the hematological variables of white blood cell count, hematocrit, serum urea nitrogen and cholesterol concentrations were examined. Serum urea nitrogen levels were lower in Se-deficient DMH-treated rats (9.6 +/- 0.7 vs. 13.7 +/- 0.9 mg/dl, P less than 0.01) and serum cholesterol was higher in Se-deficient DMH-treated animals (69.0 +/- 5.5 vs. 50.7 +/- 3.9 mg/dl, P less than 0.05). Body weights of the Se-depleted group were lower in the DMH-treated animals (P less than 0.01) although food consumption did not differ. Controls without DMH did not show differences due to Se status for any variable examined. Se deficiency appears to affect DMH toxicity but nutritional adequacy (0.1 ppm Se) does not inhibit tumor development. The results of this study do not support the belief that Se deficiency enhances colon carcinogenesis. PMID- 4032068 TI - Active absorption of selenate by rat ileum. AB - Intestinal absorption of selenate and selenite in rats was investigated in vitro by using everted sacs of the duodenum, jejunum and ileum. Only the ileal sacs incubated with selenate accumulated selenium in the serosal fluid during the incubation. Selenium transport across the ileum did not occur against a concentration gradient when selenite instead of selenate was present in the incubation medium. Sulfate and thiosulfate significantly inhibited ileal selenate transport. Decreasing the activity of the Na+,K+-ATPase, by the addition of ouabain, resulted in a significant reduction of concentrative selenate transport by the ileum. Furthermore L-leucine, but not D-glucose and D-galactose, significantly reduced selenium absorption by ileal sacs incubated with selenate. It is concluded from these results that selenate is transported actively by the ileal mucosa and that a common transport mechanism for selenate and sulfate exists. The Na+-gradient across the intestinal brush border membrane seems to be capable of energizing active ileal selenate transport. PMID- 4032069 TI - Feeding time differentially affects fattening and growth of channel catfish. AB - Channel catfish (Ictalurus punctatus) were held on a 12-h light, 12-h dark photoperiod (light onset 0600 h) and fed a nonpurified diet daily at either 0730 or 1600 h or a half ration at both of these times of day. The feeding time conducive to total growth (0730 h) differed from that conducive to fattening (1600 h). Fish fed a half ration at both times of day had body weights similar to those fed a single early meal but also had high abdominal fat weights similar to those fed a single late meal. Feeding schedule appears to be an important factor in determining the metabolic fate of nutrients. PMID- 4032070 TI - Effects of vitamins on lipid peroxidation and suppression of DNA synthesis induced by adriamycin in Ehrlich cells. AB - The effects of various vitamins on lipid peroxidation and the suppression of DNA synthesis induced by adriamycin (ADR) in vitro using Ehrlich ascites carcinoma (EAC) cells were studied. ADR produced a concentration-dependent stimulation of lipid peroxidation in EAC cells. alpha-Tocopherol and coenzyme Q10 inhibited ADR induced lipid peroxidation to about the same extent and these effects were the greatest for all antioxidants added. The inhibitory effect of riboflavin 2',3',4',5'-tetrabutyrate was greater than that of riboflavin 5'-phosphate. On measuring incorporation of [3H]thymidine into EAC cells, these vitamins did not alter appreciably the magnitude of the ADR-induced suppression of DNA synthesis in EAC cells. PMID- 4032071 TI - Effect of riboflavin-butyrate on cardiac glutathione reductase affected by adriamycin. AB - Male Wistar rats received intraperitoneal injections of adriamycin (4 mg/kg body weight/day) and/or riboflavin-butyrate (20 mg/kg body weight/day) for 6 consecutive days. Cardiac mitochondria were then prepared for our present experiment. The combined use of riboflavin-butyrate with adriamycin was evaluated for reduction of lipid peroxide formation in rat cardiac mitochondria. In order to find the mechanism of the effect of riboflavin-butyrate, the glutathione peroxidase-glutathione reductase system was examined. Adriamycin reduced the glutathione reductase activity in rat cardiac mitochondria, but did not affect the glutathione peroxidase activity. The mitochondrial content of flavin adenine dinucleotide, a prosthetic group of glutathione reductase, was greatly reduced and apoprotein of glutathione reductase also decreased. The administration of riboflavin-butyrate with adriamycin increased flavin adenine dinucleotide and glutathione reductase activity. These results suggest that exogenous administration of riboflavin-butyrate is capable of reducing lipid peroxide by both enzymatic detoxification through glutathione reductase and non-enzymatic detoxification due to direct reaction with lipid peroxide. PMID- 4032072 TI - Isolation and identification of N1-methylnicotinic acid (trigonelline) from rat urine. AB - A urinary metabolite of nicotinic acid, single- and double-labeled N1 methylnicotinic acid (trigonelline: Tg) were isolated as urinary excretion products of rats following portal vein injection of [carboxyl-14C]nicotinic acid (14C-NiA) and/or S-adenosyl-L-[methyl-3H]methionine (3H-SAM). The labeled compounds produced were identified as Tg by comparison of ultraviolet absorption pattern and chromatographic behavior with those of the authentic compound, and by cocrystallization with the authentic carrier. It was demonstrated that enzymatic synthesis of double-labeled Tg is accomplished by reaction between 14C-NiA and 3H SAM, and the enzymatic product was identified using the above methods. Approximately 1.5% respectively of the radioactivity of 14C-NiA and 3H-SAM was incorporated into Tg by enzymatic reaction. Furthermore, Tg from normal rat urine was isolated by ion-exchange chromatographic procedures and was crystallized from ethyl alcohol. The isolated compound was identified as Tg by comparison of ultraviolet spectra, infrared spectra, gas-mass spectra, elemental analysis, melting point and thin layer chromatogram behavior with those of the authentic compound. From these results, it was clearly demonstrated that Tg was one of the metabolites of nicotinic acid in the rat. PMID- 4032073 TI - Comparative changes in plasma and RBC alpha-tocopherol after administration of dl alpha-tocopheryl acetate and d-alpha-tocopherol. AB - Changes in plasma and RBC alpha-tocopherol after intravenous and oral administration of dl-alpha-tocopheryl acetate were investigated using vitamin E deficient rats and were compared with those following the administration of d alpha-tocopherol, which is the most active and natural form of tocopherol. Intravenous administration: By the administration of dl-tocopheryl acetate, the elevated plasma tocopherol levels were higher at 6 h than those elevated by d tocopherol, but the RBC tocopherol was lower 6 h after the infusion of dl tocopheryl acetate than after d-tocopherol infusion. The tocopheryl acetate incorporated into the RBCs remained for 24 h after the administration of tocopheryl acetate, the acetate then becoming undetectable in plasma. Oral administration: The tocopherol elevated in plasma and RBC was only the alpha-form and not tocopheryl acetate. In both plasma and RBCs, tocopherol levels were higher after the administration of d-tocopherol than after dl-tocopheryl acetate administration, and more was found in RBCs. PMID- 4032074 TI - Blood status and serum free amino acids in Papua New Guinea highlanders. AB - Hematological values and serum amino-acid concentrations were measured in 17 healthy male adult Papua New Guinea highlanders who live on a sweet-potato staple diet. Hematological values were within the normal range, except for a low serum urea concentration. The concentrations of serum threonine, valine, isoleucine, leucine and tyrosine were significantly lower, and those of arginine, glutamate, glycine and alanine were significantly higher, than in Japanese controls. These amino acid patterns in the serum of Papua New Guinea highlanders are an indication of low protein nutrition and adequate energy supply. Some essential amino acid and urea concentrations in the serum of nine Papua New Guinea subjects fed on an adequate protein diet (1.3 g/kg body weight, about twice their habitual diet) for 13 days were significantly increased but were still significantly lower than those of Japanese subjects. Serum alanine decreased on an adequate protein diet. These results show that amino acid uptake and utilization by peripheral tissues may be accelerated on an adequate protein diet. Blood status and serum amino acid concentrations did not show any change except for urea and some amino acids, when five Papua New Guinea highlanders were fed on a low protein diet (0.6 g/kg) consecutively for 13 days. PMID- 4032075 TI - Nutritional significance of cyclodextrins: indigestibility and hypolipemic effect of alpha-cyclodextrin. AB - Digestibility of alpha- and beta-cyclodextrin (CD) and nutritional consequences of alpha-CD and a CD mixture (n-dextrin, alpha-, beta-and gamma-CDs = 50, 30, 15 and 5% by weight) were investigated in rats. In contrast with beta-CD, alpha-CD was revealed to be indigestible. Growing rats were fed on diets supplemented with the CD mixture at 19.5, 39, 58.5 and 78% levels for 110 days, resulting in smaller weight gain and body fat deposition when they were fed on a higher CD diet. Rates of weight loss during the restricted feeding were faster in rats fed on a higher CD diet. These were due to food efficiency lowered by CD. Reduced serum and liver triacylglycerol (TG) levels were noted during a 110-day period of feeding of the CD diets, and the former was revealed due to a reduced hepatic intestinal TG secretion rate. Rats fed on a 78% CD diet, which contained alpha-CD at the 24% level, showed abnormal symptoms such as poor appetite and constipation with gas accumulation in the large intestine, and some of them died during the first 2-week feeding period. However, the surviving animals showed adaptation to the diet in the later period of the 110-day feeding. These results suggest that alpha-CD may be classified as dietary fiber which can modulate lipid metabolism in rats. Furthermore, the CD mixture may be available as a calorie substitute for weight control, which may owe mostly to alpha-CD. PMID- 4032076 TI - Effect of dietary taurine on cholesterol gallstone formation and tissue cholesterol contents in mice. AB - The inhibitory effect of dietary taurine on cholesterol gallstone formation was studied using male mice of Jcl:ICR strain. Mice were provided three kinds of semi purified diet; a cholesterol-free diet (standard), a lithogenic diet containing 0.5% cholesterol and 0.25% sodium cholate (C-CA), and a lithogenic diet supplemented with 5% taurine. The changes of total cholesterol in serum, cholesterol mass in the liver and the gall bladder, and gallstone incidence were studied as a function of time. Gallstone formation was observed only in the mice fed on the C-CA diet for more than 3 weeks. The changes of serum cholesterol concentration were not consistent with gallstone formation. The cholesterol mass of the liver in taurine-supplemented mice decreased after the 3rd week. Cholesterol content of the gall bladder increased with cholesterol gallstone formation. Therefore, the inhibitory effect of dietary taurine on cholesterol gallstone formation may be related to the decrease in cholesterol content of the liver. PMID- 4032077 TI - Comparative study of the atherogenecity of dietary trans, saturated and unsaturated fatty acids on swine coronary arteries. AB - Three groups of two-month-old swine were fed on basal diets supplemented with either oleic acid-rich safflower oil, lard or hydrogenated soybean oil in order to monitor the atherogenecity of various dietary fatty acids. The level of plasma triglyceride was highest in the safflower oil group and the level of plasma cholesterol was highest in the lard group. The degree of intimal thickening of the coronary arteries was most severe in the safflower oil group and lease severe in the hydrogenated fat group. Both the lard- and safflower oil-supplemented groups displayed lipid-rich coronary arterial lesions. The thickened intima of these two groups contained numerous activated smooth muscle cells, degenerated cells with or without stainable lipid and abundant cell debris. Cellular changes were less conspicuous in the coronary arteries from the hydrogenated fat group than in those from the other two groups. PMID- 4032078 TI - Some properties of luminal sucrase and sucrase-isomaltase complex in rat small intestine. AB - Some properties of luminal sucrase-isomaltase complex and the effect of luminal fluid on their complex were studied in rat small intestine. Luminal contents were collected by flushing the small intestine with the buffered solution. The enzyme activity was observed in luminal contents and intestinal mucosa. Sucrase and isomaltase activities were located mainly in the intestinal mucosa. However, approximately 20% of sucrase and 10% of isomaltase activities of total small intestine were found in the luminal contents. A significant amount of sucrase without isomaltase activity, the molecular weight of which was estimated at about 140,000 daltons, was found in the luminal supernatant of the distal intestine in addition to the complexed form of sucrase and isomaltase. The luminal sucrase and sucrase-isomaltase complex had similar properties such as Km values, optimal pH, molecular weights and antigenicity against anti sucrase-isomaltase antibody compared with brush border membrane-bound sucrase-isomaltase complex. Furthermore, the supernatant of the luminal contents of the ileum had a degradative effect on the isomaltase moiety of the purified sucrase-isomaltase complex and a free sucrase without isomaltase also appeared in vitro as observed in vivo. These results suggest that the sucrase-isomaltase complex is released into the intestinal lumen from the brush border membrane and that a luminal factor affects the degradation step of this enzyme as well as the biosynthesis of sucrase-isomaltase complex. PMID- 4032079 TI - Erroneous comparisons in oil refinery workers' mortality studies? PMID- 4032080 TI - Statistical validation for synthetic pyrethroid analysis. PMID- 4032081 TI - Long-term health effects following isocyanate exposure. PMID- 4032082 TI - Reactive airways dysfunction syndrome. Case reports of persistent airways hyperreactivity following high-level irritant exposures. AB - Two individuals developed an asthma-like illness after a single exposure to high levels of an irritating aerosol, vapor, fume, or smoke. Symptoms developed within a few hours. A consistent physiologic accompaniment was airways hyperreactivity, with the two subjects showing positive methacholine challenge tests. No documented preexisting respiratory illness was identified, nor did subjects relate past respiratory complaints. Respiratory symptoms and airways hyperreactivity persisted for at least four years after the incident. The incriminated etiologic agents all shared a common characteristic of being irritant in nature. Bronchial biopsy specimens showed an airways inflammatory response. This report suggests that acute high-level irritant exposures may produce an asthma-like syndrome in some individuals, with long-term sequelae and chronic airways disease. Nonimmunologic mechanisms seems to be operative in the pathogenesis of this syndrome. PMID- 4032083 TI - The 'healthy worker effect' on morbidity rates. AB - Studies relating mortality and occupation are difficult to interpret because of the "healthy worker effect." That effect is primarily due to the fact that individuals entering the labor force are in reasonably good health. A similar phenomenon might be expected in a comparison of morbidity among members of an occupational group with that of the general population. A comparison of morbidity among different population and occupation groups is made possible through the Household Interview Survey (HIS) of the National Center for Health Statistics. Data from the HIS for the years 1969 through 1974 were combined to form a sample classified according to race, sex, age, occupation, and occurrence of various health conditions. Among subjects between 25 and 59 years of age, age-specific morbidity ratios and standardized morbidity ratios were computed for blue-collar and professional/managerial employees and for unemployed who were either seeking or not seeking employment. There appears to be a "healthy worker morbidity effect" for chronic, but not for acute, conditions just as there is for mortality. The healthy worker effect for chronic morbidity maintains itself and, in fact, appears to increase throughout the 35-year period of stable employment. The age-specific morbidity ratio may have considerable theoretical importance for evaluating the related mortality experience of employed populations. PMID- 4032084 TI - Respiratory illness in the construction trades. I. The significance of asbestos associated pleural disease among sheet metal workers. AB - To assess the rate of roentgenographic and lung function abnormalities in asbestos-exposed construction workers, the authors studied 314 white male members of a local sheet metal workers union. Health outcomes were assessed by questionnaire, simple spirometry, and chest roentgenography; data were collected and interpreted following guidelines of the American Thoracic Society and the International Labor Office. Analyses of union records showed the tested population to be representative of all those eligible for testing. Pleural abnormalities were common, increasing to a prevalence of approximately 70% in workers with more than 30 years employment. Roentgenographic evidence of pleural disease was significantly correlated with decreased forced vital capacity (p = 0.027) after controlling for the potential confounding effects of age, height, cigarette consumption history, and employment duration. In contrast, forced expiratory volume in 1 s showed a stronger association with amount smoked (p = 0.022) than with pleural abnormality (p = 0.316). Logistic regression analyses showed that cigarettes act to increase the effect of asbestos in causing pleural disease among exposed workers. Cigarettes, in the absence of significant asbestos exposure, do not appear to cause pleural disease. The authors conclude that construction workers, such as those described herein, have a considerably increased rate of pleural disease, which has functional significance in view of the correlations noted with forced vital capacity measurements. Therefore, pleural disease in asbestos-exposed workers is not only an indicator of exposure but also an indicator of early impairment of pulmonary function. PMID- 4032085 TI - Reproductive outcomes in women exposed to solvents in 36 reinforced plastics companies. I. Menstrual dysfunction. AB - Recent studies have suggested that exposure to styrene monomer and other solvents is associated with menstrual disturbances. This is the first U.S. study to evaluate the effects of exposure to styrene on dysmenorrhea, intermenstrual bleeding, secondary amenorrhea, menstrual blood clots, and hypermenorrhea. A comprehensive questionnaire was administered to 1,535 blue-collar workers. Multiple logistic regression analyses did not reveal a positive association between styrene exposure and any menstrual abnormality. Risk factors associated with menstrual disturbances included chronic illness with secondary amenorrhea (p less than or equal to .005), nulliparity with both decreased blood clots (p less than or equal to .005) and hypermenorrhea (p less than or equal to .001), smoking with blood clots (p less than or equal to .005), and age with hypermenorrhea (p less than or equal to .001). The overall prevalences of menstrual disorders were 14% for dysmenorrhea, 16% for intermenstrual bleeding, 7% for secondary amenorrhea, 40% for menstrual blood clots, and 31% for hypermenorrhea. PMID- 4032086 TI - Notification and risk assessment for bladder cancer of a cohort exposed to aromatic amines. III. Mortality among workers exposed to aromatic amines in the last beta-naphthylamine manufacturing facility in the United States. AB - A retrospective cohort mortality study was conducted among workers employed at the last facility in the United States that manufactured beta-naphthylamine (BNA), a recognized human bladder carcinogen. This study was conducted in conjunction with a pilot project in which workers were notified of the health risks associated with exposures to carcinogenic amines. Cause-specific mortality for 1,312 male workers employed between 1940 and 1972, and followed through 1979, was compared with the mortality of the general population in the United States. Two deaths from bladder cancer were observed while 0.7 such deaths were expected. Due to the use of these potent carcinogenic amines, it had been anticipated that more bladder cancer deaths would be found in this population. The reasons for the small number of bladder cancer deaths could have been the low percentage of the work force exposed, an inadequate latency period, and/or the high survival rate for bladder cancer. In fact, a notification and medical screening project recently conducted in this same population found an additional 11 bladder cancer cases. This suggests that mortality may not always be an adequate indicator of disease risk. PMID- 4032087 TI - Respiratory function and exposure-effect relationships in wood dust-exposed and control workers. AB - The effect of wood dust exposure on 50 cabinet makers was examined. Woodworkers reported more nasal and eye symptoms and more cough, sputum and wheezing than did 49 control workers. More irritated cells were present in the woodworkers' nasal cytological smears. In contrast to the control workers, the woodworkers had a significant decline in lung function over the workshift. An inverse correlation between baseline lung function and an exposure index (mean area dust level multiplied by length of exposure) was demonstrated in the woodworkers. Greater dust exposure was not associated with larger falls in lung function over the work shift. PMID- 4032089 TI - Psychology in health risk messages for workers. AB - The content, style, and mode of company communications directed to workers regarding job hazards and health risks are frequently based only on concerns for technical accuracy and legal liability. These considerations as shaping factors in informational messages do not ensure worker understanding and responsiveness. Moreover, the uncertainty of health threats posed by many workplace chemical and physical agents, and the delayed, insidious disorders they may portend, present formidable obstacles in this regard. This report describes guidelines that attempt to overcome these difficulties, with specific reference to printed forms of informational material. The guidelines are based on concepts from the cognitive and social psychology literature, with additional input from experts in those fields as well as representatives from management and labor who have responsibilities for worker health education in their respective organizations. Selected guidelines are presented and critiques are offered of samples of hazard information materials directed to workers in light of the guidelines' prescriptions. Field trials are planned as a follow-up. PMID- 4032088 TI - A retrospective cohort mortality study of iron ore (hematite) miners in Minnesota. AB - In a retrospective cohort mortality study of 10,403 Minnesota iron-ore (hematite) miners no excesses of lung cancer mortality were found among either underground (Standardized mortality ratio [SMR] = 100) or above ground (SMR = 88) miners. Yugoslav-born miners incurred a two-fold significant excess mortality for lung cancer that did not appear to be associated with their mining exposures. Significant excesses in mortality due to stomach cancer were found for both underground (SMR = 167) and aboveground (SMR = 181) miners as compared with U.S. white males. However, except among Finnish-born miners, these excesses disappeared when comparisons were made with the appropriate county rate. The apparent absence of significant radon exposure, a strict smoking prohibition underground, an aggressive silicosis control program, and the absence of underground diesel fuel use may explain why these underground miners did not appear to incur the lung cancer risk reported in other studies. PMID- 4032090 TI - Effect of shiftwork on canteen food purchase. AB - Shiftwork has the potential for altering food intake patterns in ways that may be unfavorable to health. In two industrial plants in the Australian state of Victoria where food had to be brought from home or purchased on the job, the effect of shiftwork on food sources as well as the energy density of food items was assessed. In the steel plant, employees on the afternoon shift had relatively more principal eating occasions on the job than did day or night shift workers. The canteen did not cater adequately for the meal needs of employees, who used the vending machines to a greater extent when on the afternoon shift than on other shifts. In the aluminum plant, workers who depended on food from home alone ate relatively less energy-dense foods than did workers who included canteen foods in their diets. Use of lower-energy density items was greater on the day shift than on the afternoon shift, and in turn was greater on that shift than for the night shift. After a one-year nutrition education program, the use of lower energy density items increased on the day and night shifts. Thus, it was found that food usage could be influenced not only by shiftwork, but also by the food facility available on site and by a nutrition education program. PMID- 4032091 TI - Fitting relationships between exposure and standardized mortality ratios. AB - Practical methods are described for formal fitting of simple (linear) relationships between exposures in several subgroups and standardized mortality (or morbidity) ratios (SMRs) for these groups, whether derived from a cohort study by the person-years method or otherwise. The observed events are assumed to have Poisson variation about the fitted relationships. Procedures are outlined for obtaining parameter estimates by iterative weighted least squares regression, which is not only equivalent to, but also the simplest form of maximum likelihood estimation. A test of fit is available in a chi 2 statistic for deviations of observed data from "fitted" values. A further test allows one to examine whether the SMR at zero exposure is different from unity. The concept of relative slopes is discussed, and methods are given for obtaining estimates and confidence intervals. Generalizations to more than one exposure, and to quadratic and other relationships, are explained. Steps for computing the basic fits are detailed, and instructions for adapting packaged computer programs given. Illustrations are provided from data of lung cancer SMRs in relation to exposure to asbestos and to smoking. PMID- 4032092 TI - Risk of encephalopathia among retired solvent-exposed workers. A case-control study among males applying for nursing home accommodation or other types of social support facilities. PMID- 4032093 TI - Occupational and psychosocial stress among commercial aviation pilots. AB - The sources of occupational and domestic stress, together with life events and coping strategies, were assessed in terms of their influence on job dissatisfaction, mental health, and performance among a group of 442 commercial airline pilots. It was found that self-perceived poor performance was associated with job-related factors such as fatigue and anxiety about required courses, performance checks, and insufficient flying time, particularly among older pilots. Job dissatisfaction was predicted by lack of career opportunities, poor organizational climate and morale, and lack of autonomy at work, together with some domestic stressors (e.g., family health). Overall mental ill-health was found to be associated with lack of autonomy at work, fatigue, and flying patterns, together with an inability to relax and a lack of social support. PMID- 4032094 TI - A cohort study of employees of a manufacturing plant using trichlorethylene. AB - A prospective study was conducted of 2,646 employees who worked three months or more during the period January, 1957, through July, 1983, in a manufacturing plant that used trichlorethylene as a degreasing agent throughout the study period. Ninety-eight percent of the study cohort were traced; they accounted for 16,388 person-years of employment and 38,052 person-years of follow-up. Mortality experience was found to be generally more favorable than that of the comparable segment of the U.S. population over the same period of time. For the white male cohort there were fewer deaths than expected from heart disease, cancer, and trauma (standard mortality rate for all causes = 0.79, p less than .01). Reports by current and former employees of health problems requiring medical treatment showed that there were only one third as many persons with heart disease or hypertension as were reported in a comparable reference population studied over the past five years. PMID- 4032095 TI - Temporal properties of visual channels measured by masking. AB - Threshold elevations for spatially localized test stimuli were measured as a function of the temporal frequency of a sinusoidal mask grating. Ten of these temporal-masking curves were determined, each using a test stimulus of different temporal frequency. It was found that these data could be accounted for by four temporal-tuning curves: one low-pass curve with a corner frequency of 8.0 Hz and three bandpass curves with bandwidths of 2.0-2.5 octaves and peaks all within the region 4.0-8.0 Hz. In another set of experiments, a series of 1 spatial-masking curves was determined, each using a test stimulus of different spatial frequency. Measurement of the entire series was repeated using 1.0- and 8.0-Hz mask temporal modulations. Spatial-masking data collected under the two temporal conditions could both be accounted for by a single set of seven spatial-tuning curves, without changing the shape of any of these curves. The data are therefore compatible with spatiotemporal separability. Finally, a large set of contrast response curves (threshold elevation as a function of mask contrast) was collected. These curves were found to follow a power law whose exponent varied with the spatiotemporal conditions of the experiment. PMID- 4032096 TI - Accommodation-dependent model of the human eye with aspherics. AB - We consider a schematic human eye with four centered aspheric surfaces. We show that by introducing recent experimental average measurements of cornea and lens into the Gullstrand-Le Grand model, the average spherical aberration of the actual eye is predicted without any shape fitting. The chromatic dispersions are adjusted to fit the experimentally observed chromatic aberration of the eye. The polychromatic point-spread function and modulation transfer function are calculated for several pupil diameters and show good agreement with previous experimental results. Finally, from this schematic eye an accommodation-dependent model is proposed that reproduces the increment of refractive power of the eye during accommodation. The variation of asphericity with accommodation is also introduced in the model and the resulting optical performance studied. PMID- 4032097 TI - Continuous subcutaneous insulin infusion (CSII). PMID- 4032098 TI - Eliminating pharmacists' calls. PMID- 4032099 TI - Production and utilization of physicians in Oklahoma. PMID- 4032100 TI - Age-related changes in articular cartilage proteoglycans: electron microscopic studies. AB - Biochemical and biophysical studies have demonstrated that proteoglycan monomers from immature and adult articular cartilage differ in composition and size. To investigate the structural basis of age-related differences in articular cartilage proteoglycan monomers and aggregates, we isolated and purified high buoyant density proteoglycans from the articular cartilages of 2- to 3-month-old calves and 18-month-old steers. The molecular architecture and dimensions of the proteoglycans were examined using the electron microscope monolayer method. Aggregated and nonaggregated monomers from calf cartilage were longer and less variable in length than the corresponding monomers from steer articular cartilage. Calf monomer lengths had unimodal frequency distributions whereas nonaggregated steer monomer lengths had a bimodal distribution. These observations were confirmed by acrylamide-agarose electrophoresis, which demonstrated that the samples contained only one species of proteoglycan monomer in calf but two species in steer. In addition, calf aggregated monomers had longer thin segments indicating that calf and steer monomers differed in structure as well as in size. Steer proteoglycan aggregates were shorter and had fewer monomers than those from calf. These observations demonstrate the existence of significant age-related structural differences in articular cartilage proteoglycans and form the basis for future study of the mechanisms responsible for these differences. PMID- 4032101 TI - Effects of spinal fusion on the proteoglycans of the canine intervertebral disc. AB - Posterior lumbar two-level spinal fusion was undertaken in 10 mature beagles. The animals were sacrificed 6 and 12 months later. Two months before sacrifice control and experimental animals received intravenously Na2(35)SO4 (1 mCi/kg). Discs encompassed by the fusion and those adjacent to it were dissected into the nucleus pulposus and annulus fibrosus (AF), which were analysed separately. Proteoglycans (PGs) were extracted with 4.0 M guanidine HCl and purified by CsCl density gradient ultracentrifugation. The hydrodynamic size and ability of the PG subunits to aggregate in the presence of hyaluronic acid were investigated by Sepharose CL-2B chromatography. The PG subunits were analysed for their galactosamine (galN), glucosamine (glcN), hexuronic acid, and protein content or were subjected to digestion with papain or chondroitin-ABC-lyase to establish the size of the chondroitin (CS) and keratan (KS) sulphate chains and the KS-PG core protein complex. Decreased ability to aggregate of PGs isolated from discs 6 and 12 months after surgery was demonstrated. While their hydrodynamic size after 6 months was generally the same or smaller than those in control tissues, the PG population present after 12 months was larger, particularly in the AF. Analysis of PG subunits from fusion discs afforded galN/glcN, galN/protein, and hexuronic acid/protein ratios that were compatible with the presence in these tissues of PGs in which the proportion of CS attached to core protein was greater than in control tissues. These studies provide the first experimental evidence that a metabolic response of discs in a fused segment may be accompanied by the biosynthesis of a new PG population whose structure is similar to that present in immature tissues. PMID- 4032102 TI - Biomechanical time-tolerance of fresh cadaveric human spine specimens. AB - Changes in the biomechanical properties of fresh cadaveric spinal specimens due to long-term freeze storage and long test periods have been investigated. Fresh cadaveric specimens were divided into three groups: Group A specimens were tested fresh on the 1st day and 13 subsequent days; Group B specimens were tested on the 1st day, frozen in sealed bags at -18 degrees C for 21 days, and tested for 13 consecutive days after thawing; and Group C specimens were frozen for up to 232 days and tested for 14 consecutive days after thawing. We could not find any significant differences between the behavior of the three test groups. This implies that freezing and storage, even for long periods, do not significantly alter the physical properties of cadaveric spinal specimens. Concerning the differences observed on a daily basis, the mean value of the maximum displacement for the 1st day did not differ significantly from the corresponding mean value for the 13 consecutive days. This was true for all three groups, although there was some indication that the fresh group specimens showed greater variation than the two frozen groups. PMID- 4032103 TI - Evidence for different sources of stress-generated potentials in wet and dry bone. AB - Physiologically moist bone and dry bone behave differently when tested for electrical response to cantilever bending. To characterize this difference more precisely, voltages were generated in the same specimen in each of the two states via the same testing procedure--changing the electrode-to-force distance by moving the electrodes and holding the force position constant. In the dry state, a non-systematic pattern of voltages versus electrode position was generated. In the wet state, a linear relationship was found. Furthermore, the sign of the concave positive regions reversed to concave negative on wetting the specimen. The implication is that different electromechanical transduction mechanisms are involved in the wet and dry cases. The dominant mechanism in the wet case is taken to be the streaming potential rather than piezoelectricity. PMID- 4032104 TI - Monitoring the healing of a tibial osteotomy in the rabbit treated with external fixation. AB - Fracture site axial rigidity was monitored non-destructively at weekly intervals during healing of tibial osteotomies in adult rabbits. Two groups of 20 rabbits each were treated with external fixators of two different rigidities. Four animals from each group were killed at 3, 5, 6, 7, and 8 weeks to determine the bending moments at failure of the healing fractures. Normal fracture healing was accompanied by characteristic phases in the development of fracture site axial rigidity. From 0 to 3 weeks there was a period of low and approximately constant rigidity, followed by a linear increase during 3 to 5 weeks to an approximately three to four times greater rigidity. The maximum average normalized axial rigidities were reached at 6 weeks and were 57% (high rigidity group) and 77% (low rigidity group) of the untreated contralateral controls. The maximum average normalized failure moments occurred at 8 weeks and were 48% (high rigidity) and 44% (low rigidity) of controls. The differences due to fixator rigidity were not statistically significant except for a large increase in failure moments at 3 weeks for the low rigidity group. Axial rigidities were correlated (r2 = 0.74 and 0.53, respectively) with failure moments, but only during the first 6 weeks. The monitoring technique provides a nondestructive means for following the biomechanical progress of fracture healing in an animal model. The occurrence of the characteristic increase in fracture site axial rigidity at 3 to 5 weeks can also be used to distinguish between normal and abnormal healing. PMID- 4032105 TI - Parametric analyses of pin-bone stresses in external fracture fixation devices. AB - Problems occurring in the use of external fixators for bone fractures include pin bone interface necrosis, infection, and loosening. These may be initiated and enhanced by pin-bone interface stress levels. Based on stress data from finite element method (FEM) models, an analytical "closed-form" model of the local pin bone configuration in long-bone fracture fixation is developed. This model is relatively simple and useful for routine applications in combination with clinical studies and animal experiments. Although approximate, the most significant stress predictions in the pin-bone structure compare well with more sophisticated FEM analysis results. The analytical model is used for extensive parametric analyses, investigating the effects on the pin-bone interface stress distribution of frame configuration parameters, pin diameter and modulus, bone dimensions, and elastic characteristics. The results indicate that these stresses may reach very high levels under unfavorable circumstances but can be drastically reduced by increasing the bending rigidity of the pin, reducing the side-bar separation and applying full-pin configuration in favor of half-pins. PMID- 4032106 TI - Repeatability of phasic muscle activity: performance of surface and intramuscular wire electrodes in gait analysis. AB - Repeatability is an important consideration for gait analysis data that are being used as an adjunct to clinical decision making. An index of repeatability may be based on a statistical criterion (variance ratio) that reflects similarity of wave forms over a number of identical cycles. The purpose of this study was to use the variance ratio to assess the repeatability of phasic muscle activity recorded with surface and bipolar intramuscular wire electrodes during gait on 10 normal subjects. Variance ratios were calculated using rectified and smoothed electromyographic data recorded simultaneously from the two types of electrodes. Three measures of repeatability (reproducibility, reliability, and constancy- defined as the cycle-to-cycle, run-to-run, and day-to-day repeatability of phasic muscle activity) were used to compare the performance of the two electrode techniques. Results show that the reproducibility and reliability were better for surface electrodes than for intramuscular wire electrodes, and constancy was good for surface electrodes and poor for intramuscular wire electrodes. Repeatability improved with increasing smoothing window lengths but was better for surface electrodes than wire electrodes, irrespective of the smoothing window. This study indicates that surface electrode data represent a more consistent measure of activity of superficial muscles, if comparisons are to be made between gait data from different test days. PMID- 4032107 TI - Stress analyses of joint arthroplasty in the proximal humerus. AB - Finite element stress analyses were performed on the proximal humerus before and after the simulated implantation of stemmed, metallic prosthetic components with porous sintered surfaces for direct bony attachment. Design geometries with surfaces at the prosthetic head/bone interface that were (a) convex, (b) flat, and (c) concave were studied. Analyses for each of the three geometries were conducted to reflect (a) bone ingrowth on all the prosthesis/bone surfaces and (b) bone ingrowth only along the underside of the prosthetic humeral head (assuming the stem was not coated with a porous material). Three loading conditions were used to model various degrees of abduction of the arm. Results indicated that in the normal humerus the compressive joint forces are transmitted from the articular surface through cancellous bone to the inferior cortical shell. Contraction of the rotator cuff muscles created tensile stresses in the superolateral cancellous bone and the superior cortical shell of the humerus. Results of the implanted humeral component models indicated that the use of a prosthesis with bone ingrowth along the stem would cause marked stress shielding proximally whereas the use of implants with porous ingrowth only on the underside of the humeral head replacement produced stress fields more similar to the normal humerus. The convex, flat, and concave surfaces provided similar load transfer from the component to the underlying bone in all loading cases. Other prosthetic head designs that may offer better initial stability produced stress fields similar to those of existing prostheses. PMID- 4032108 TI - Effects of prosthetic acetabular replacement on strains in the pelvis. AB - The effects of cemented acetabular components on the strains in the pelvis were determined experimentally. Four components were tested: A plain metal hemisphere; a metal hemisphere with a triflange; a hemisphere with an iliac peg; and a hemisphere with a complete flange and a peg. Loading was carried out in neutral, flexion, and extension directions. The subchondral bone was only slightly reamed, and components were cemented and tested successively. For the intact hip joint, the strains on the superior acetabular rim were much lower than those on the posterior rim. After placement of the components, the tensile strains on the rim decreased by 22-54% while the compressive strains increased by 0-25%. The bone on the medial inferior surface was subjected to 65% less tensile strain and 48% more compressive strain in neutral and extension loading. There were no great differences between the four styles of acetabular component. PMID- 4032109 TI - Workshop on the bone-joint implant interface. AB - A workshop on the bone-implant interface, as related to loosening of total joint implants, was held in Chicago on September 14-16, 1983. More than 60 orthopaedic clinicians and researchers and basic connective tissue biologists met to review problems and potential solutions to joint implant loosening. The following is a synopsis of the presentations and discussions. PMID- 4032110 TI - [Clinical significance of the subsets of lymphocyte in the peripheral blood of the head and neck cancer patients]. PMID- 4032111 TI - [Histochemical study of the glycoconjugates in human upper airway mucosa]. PMID- 4032112 TI - [A case of malignant melanoma in the external auditory canal followed by systemic vasculitis]. PMID- 4032113 TI - [Nasal respiratory resistance in healthy adults using oscillation method]. PMID- 4032114 TI - [Infectious mononucleosis in otorhinolaryngology]. PMID- 4032116 TI - [Experimental study of the vibration analysis of the receivers of the bone conduction hearing aids by holographic interferometry]. PMID- 4032115 TI - [Sensori-neural hearing loss due to mumps--non-severe cases]. PMID- 4032117 TI - [The study of host defense mechanisms of the nose. Third report: absorption of an antigen from the nasal mucosa]. PMID- 4032118 TI - [A Basic study of the deglutition reflex mechanism]. PMID- 4032119 TI - [Phasic components of isolated frog utricle and the effect of ototoxic drugs]. PMID- 4032120 TI - [Carcinoma of the tonsil. Analysis of 54 cases]. PMID- 4032121 TI - [Analysis of the stabilogram using the rolling platform]. PMID- 4032123 TI - [Effects of infrasound on the human body]. PMID- 4032122 TI - [Analysis of gaze stabilization during stepping and running]. PMID- 4032124 TI - The response of small blood vessels in rat skin and skeletal muscle to repeated application of histamine: a chemical, topographical and electron microscopic study. AB - Quantitative studies of increased vascular permeability, employing vascular labelling with colloidal carbon and measurement of the rate of escape of intravascular 99Tc labelled antimony sulphide (Sb2S3) colloid, show that local injection of histamine into the skin or cremaster muscle of rats reduces for a period of 6-8 h the leakage induced by a second injection of histamine into the same site. Electron microscope studies employing multiple marker particles show that individual blood vessels are able to respond to two successive applications of histamine, and that the diminished leakage seen after the second injection is due to a reduced response of individual vessels and not to leakage from vessels unaffected by the first injection. Prior administration of bradykinin does not reduce the response to local injection of histamine into rat skin. The result suggest that sustained release of histamine is unlikely to be important in the production of prolonged increase in vascular permeability in acute inflammation. Bradykinin may be involved in such response but the findings provide no evidence for its participation. PMID- 4032125 TI - The histopathology of the larynx in the neonate following endotracheal intubation. AB - Subglottic stenosis is the most common serious complication of endotracheal intubation in the neonate with an incidence of between 1-8 per cent. While considered a complication of traumatic injury to the larynx and possibly associated with prolonged intubation, the pathogenesis is poorly understood and the pathology has not been described in detail. The nature of intubation induced injury has been investigated by examining step-sections of 43 larynges removed from neonates post-mortem who had been intubated for periods ranging from 10 min to 12 weeks. Focal ulceration was identified in the supraglottis and the anterior glottis. Similar injury was seen in the posterior glottis and subglottis but with more prolonged intubation there was full thickness mucosal necrosis, perichondritis and partial destruction of the arytenoid and cricoid cartilages. Although the severity of the injury progressed with time and many of the most severe injuries occurred early, in the second and third weeks of intubation, the larynx usually healed despite the continued presence of the endotracheal tube. Prolonged intubation on its own does not appear to be an important factor in the production of severe laryngeal injury nor, therefore, the subsequent complications such as subglottic stenosis. PMID- 4032126 TI - Quantitative and ultrastructural study of Leydig cells in Klinefelter's syndrome. AB - This ultrastructural and quantitative study of Leydig cells in Klinefelter's syndrome has been performed using the entire testes obtained from four autopsies plus testicular biopsies from 20 patients. The total Leydig cell volume per testis in Klinefelter's syndrome was similar to that of control testes. However, the total number of Leydig cells per testis was significantly lower in the patients with Klinefelter's syndrome than in the controls. This may be attributed to the Leydig cell hypertrophy that these patients underwent. In patients with Klinefelter's syndrome the average volume of each Leydig cell was significantly higher than that of the controls. Electron microscopic findings revealed that besides ultrastructurally normal Leydig cells there were three other morphologically abnormal Leydig cell types: abnormally differentiated cells; multivacuolated cells; and immature Leydig cells. The ultrastructurally normal Leydig cells were probably the cells principally responsible for testosterone biosynthesis in these patients, whereas the other Leydig cell types were probably barely or not at all functional. The hypertrophy showed by the ultrastructurally normal Leydig cells may be interpreted as an attempt to increase testosterone production. PMID- 4032127 TI - Lipid in the human gallbladder mucosa. A histochemical study by light and electron microscopy. AB - The distribution of lipids in the epithelium of 70 gallbladders removed for cholecystitis was investigated histochemically. Lipid was demonstrated in 68 gallbladders--cholesterol and its esters, triglycerides, free fatty acids and phospholipids. Neutral lipid was found at the bases of epithelial cells in 90 per cent and at the apex in 10 per cent of the gallbladders. Phospholipid was shown at the apex of epithelial cells in 64 per cent of the gallbladders. Electron microscopy in 12 specimens revealed cholesterol in and between the epithelial cells and in the underlying connective tissue. PMID- 4032128 TI - The gastro-duodenal epithelium in peptic ulceration. AB - Mucosa-related bacteria, intra-epithelial lymphocytes and intra-epithelial polymorphonuclear leucocytes have been studied in 35 patients with duodenal ulceration, 27 patients with gastric ulceration and eight control subjects with normal gastro-duodenal mucosa. Mucosa-related bacteria were found in approximately 80 per cent of peptic ulcer patients and rarely in controls. The bacteria were most numerous at the sites of active chronic gastritis. There was a positive correlation between the number of bacteria and the number of intra epithelial polymorphonuclear leucocytes. There was no correlation between the peripheral blood white cell count and the number of intra-epithelial polymorphonuclear leucocytes. The number of intra-epithelial lymphocytes was increased in peptic ulceration. PMID- 4032129 TI - Defective humoral immunity in pediatric acquired immune deficiency syndrome. AB - Specific antibody production was assessed in six young children with the acquired immune deficiency syndrome (AIDS). All patients were immunized with bacteriophage phi X 174, a T cell-dependent neoantigen. In addition, antibody responses to pneumococcal vaccine and tetanus toxoid, lymphocyte responses to mitogens, and serum immunoglobulin levels were determined. Polyclonal hypergammaglobulinemia was documented in three patients. Responses to bacteriophage phi X 174 were abnormal in all patients: primary responses were blunted, secondary responses were markedly decreased, and the class switch (IgM-IgG) was absent in five of six patients. Antibody formation to pneumococcal vaccine and tetanus toxoid was also diminished. Lymphocyte mitogenic responses to phytohemagglutinin, concanavalin A, pokeweed mitogen, and staphylococcal Cowan A were generally decreased. These findings confirm that pediatric patients with AIDS have significant abnormalities in humoral immunity. Dysfunction of both T cells and B cells plays a role in the resultant poor specific antibody production. PMID- 4032131 TI - Pulse oximetry in pediatric intensive care: comparison with measured saturations and transcutaneous oxygen tension. AB - We evaluated a new pulse oximeter designed to monitor beat-to-beat arterial oxygen saturation (SaO2) and compared the monitored SaO2 with arterial samples measured by co-oximetry. In 40 critically ill children (112 data sets) with a mean age of 3.9 years (range 1 day to 19 years), SaO2 ranged from 57% to 100%, and PaO2 from 27 to 128 mm Hg, heart rates from 85 to 210 beats per minute, hematocrit from 20% to 67%, and fetal hemoglobin levels from 1.3% to 60%; peripheral temperatures varied between 26.5 degrees and 36.5 degrees C. Linear correlation analysis revealed a good agreement between simultaneous pulse oximeter values and both directly measured SaO2 (r = 0.95) and that calculated from measured arterial PaO2 (r = 0.95). The device detected several otherwise unrecognized drops in SaO2 but failed to function in four patients with poor peripheral perfusion secondary to low cardiac output. Simultaneous measurements with a tcPO2 electrode showed a similarly good correlation with PaO22 (r = 0.91), but the differences between the two measurements were much wider (mean 7.1 +/- 10.3 mm Hg, range -14 to +49 mm Hg) than the differences between pulse oximeter SaO2 and measured SaO2 (1.5% +/- 3.5%, range -7.5% to -9%) and were not predictable. We conclude that pulse oximetry is a reliable and accurate noninvasive device for measuring saturation, which because of its rapid response time may be an important advance in monitoring changes in oxygenation and guiding oxygen therapy. PMID- 4032130 TI - Effect of diet and controlled exercise on weight loss in obese children. AB - The effects of adding exercise to diet for weight control in obese children were evaluated by randomizing obese girls to one of two groups: diet and diet plus exercise. During the first 6 weeks of the treatment, children exercised in a supervised three times a week exercise program, in which they walked or ran 3 miles. Significant decreases from baseline weight and in percent overweight were observed for both groups during the year of treatment. Significant decreases in percent overweight were observed at 0 to 2 months and then at 2 to 6 months for the children who were exercising, whereas percent overweight in children in the diet-alone group decreased only from 0 to 2 months. In addition, a significant improvement in fitness was observed only for children in the diet plus exercise group. PMID- 4032132 TI - Discontinuation of bee venom immunotherapy in children and adolescents. AB - Sixty-six patients with a history of systemic allergy reactions to bee stings, positive skin prick test to less than or equal to 100 micrograms/ml bee venom, and positive radioallergosorbent test (RAST) results were given venom immunotherapy. IgE and IgG antibodies to bee venom were measured by RAST and enzyme-linked immunosorbent test (ELISA), respectively. IgE and IgG anti-bee venom levels rose initially, but subsequently fell during immunotherapy. In 31 patients in whom specific IgE fell to low (less than 6% counts bound) or unmeasurable levels, immunotherapy was discontinued, and sting challenge was carried out 1 to 3 years later. All patients tolerated sting challenge well. The specific IgE and IgG antibody levels did not change significantly after treatment was stopped. Our data suggest that hyposensitization treatment can be stopped when specific IgE serum concentrations have fallen to low or unmeasurable levels and specific IgG antibody values are maintained, and that in a considerable number of patients venom immunotherapy has a lasting therapeutic and immunologic effect. PMID- 4032133 TI - Age-related alterations in immunoreactive pancreatic lipase and cationic trypsinogen in young children with cystic fibrosis. AB - Serum immunoreactive pancreatic lipase and cationic trypsinogen are elevated in young infants with cystic fibrosis (CF) and may be useful neonatal screening tests for CF. We compared lipase measured by a recently developed ELISA immunoassay with trypsinogen measured by radioimmunoassay in 70 children (ages 0.1 to 9.9 years) with CF who had various degrees of pancreatic dysfunction and in 79 similarly aged children without CF (controls). In the control children, lipase activity increased with advancing age, whereas trypsinogen showed no age related trend. Lipase and trypsinogen were significantly elevated in the infants with CF who were younger than 1 year, irrespective of pancreatic function (trypsinogen, P less than 0.001; lipase, P less than 0.05). Sensitivities in detecting CF were 76% and 90% for lipase and trypsinogen, respectively. After the first year of life, lipase and trypsinogen values declined toward normal, the rate of decline of lipase being greater than that of trypsinogen; 67% of lipase values were within or below the normal range by 3 years, whereas 67% of trypsinogen values continued to be elevated. We conclude that trypsinogen is an excellent screening test for CF in young infants regardless of pancreatic function, and that the addition of a serum pancreatic lipase determination does not improve the accuracy of trypsinogen as a screening test for cystic fibrosis. PMID- 4032134 TI - Pseudomonas cepacia colonization in patients with cystic fibrosis: risk factors and clinical outcome. AB - During the period of 1979 to 1983, 38 patients with cystic fibrosis (CF) at the CF center of St. Christopher's Hospital for Children in Pennsylvania developed respiratory tract colonization with Pseudomonas cepacia. Seventeen (45%) of the patients with colonization died. Yearly incidence rates of P. cepacia colonization fluctuated between 1.3% and 6.1%, suggesting an endemic phenomenon. Case-control studies showed that severe underlying CF, use of aminoglycosides, and having a sibling with CF and P. cepacia colonization were significant risk factors for P. cepacia colonization. Once colonized with P. cepacia, patients with CF were likely to be hospitalized longer (P = 0.008) and to die sooner (P = 0.0001) than control patients with CF. Environmental and microbiologic studies did not identify a common source or mode of transmission of P. cepacia among patients. The results of this investigation suggest that P. cepacia colonization of patients with CF was endemic in the hospital, occurred more frequently in those with severe disease, and was associated with adverse clinical outcome. PMID- 4032135 TI - Octanoic acidemia and octanoylcarnitine excretion with dicarboxylic aciduria due to defective oxidation of medium-chain fatty acids. AB - Five patients aged 7 to 21 months are described who developed attacks of coma after a short prodromal illness with diarrhea or vomiting or both. Four had concomitant hypoglycemia, and all had hypoketonemia, with excessive urinary excretion of medium-chain dicarboxylic acids, medium-chain (omega-1) hydroxyacids, suberylglycine, hexanoylglycine, and octanoylcarnitine. All patients accumulated octanoic acid, decanoic acid, and cis-4-decenoic acid in plasma. Fibroblasts from three patients showed a decreased rate of octanoate oxidation (10%, 12%, and 29% of control values, respectively). These findings suggest a deficiency of medium-chain acyl-CoA dehydrogenase, most probably an autosomal recessive inherited metabolic disorder. Two of the patients died during an acute attack, and a third had severe neurologic sequelae; the two remaining patients recovered. Plasma free carnitine levels were low, but total carnitine was normal. The three surviving patients underwent a fasting test, which did not lead to hypoglycemia, although hypoketonemia, dicarboxylic aciduria, and excessive mobilization of fatty acids did occur. The surviving patients were maintained on frequent carbohydrate-enriched meals. PMID- 4032136 TI - Symptomatic hypomagnesemia in cystic fibrosis. PMID- 4032137 TI - Fortified mothers' milk for very low birth weight infants: results of growth and nutrient balance studies. AB - Mothers' milk, fortified daily with skim and cream components derived from mature donor human milk, was fed fresh during the first 2 postnatal months to 18 (group FMM) healthy, very low birth weight (VLBW) infants. Following the same feeding protocol, 16 additional VLBW infants were fed commercial formula that had a similar range of energy and nitrogen. Infants were evaluated for growth, metabolizable energy, balances of nitrogen and fat, and biochemical markers of nutritional status. Growth measurements from birth to 1800 gm were similar in the two groups. Nutritional balance was performed at approximately 2.5 (first study period) and 6 (second study period) weeks. Metabolizable energy (average 109 kcal/kg/day) was similar in both groups and met theoretical needs of the growing VLBW infant. Apparent nitrogen retention was similar and equivalent to estimates of intrauterine nitrogen accretion (approximately 325 mg/kg/day). Fat absorption increased from the first (70% of intake) to the second study (80% of intake) and was similar in both groups. Serum values for albumin, total protein, prealbumin, hemoglobin, and creatinine were also similar, and declined with increases in postnatal age. Significant differences were observed between feeding groups for serum phosphorus and calcium. These results indicate that healthy VLBW infants maintain adequate growth and macronutrient balance for the first 2 months postnatally when fed mothers' milk fortified with additional skim and cream components. PMID- 4032138 TI - Congenital diaphragmatic hernia: arterial structural changes and persistent pulmonary hypertension after surgical repair. AB - Some infants with congenital diaphragmatic hernia who die after surgical correction have a transient postoperative period during which systemic oxygenation is adequate (honeymoon period), whereas others have persistent hypoxemia. Using morphometric techniques, we analyzed lung structure, especially the arterial bed, in seven infants who died within 1 week of surgical repair. Three infants comprised the honeymoon group, the PaO2 transiently being greater than 150 mm Hg in the descending aorta (FiO2 1.0); four infants comprised the no honeymoon group and never had PaO2 greater than 85 mm Hg. All lungs were hypoplastic for age; with one exception, infants in the no-honeymoon group had smaller lungs. Arterial structure in the no-honeymoon group contributed to a greater reduction in pulmonary arterial cross-sectional area. Each infant in the no-honeymoon group had muscularization of intra-acinar arteries and failure of perinatal increase in compliance of small preacinar arteries, features not seen in the honeymoon group or in the normal newborn infant. In addition, compared with the honeymoon group, luminal area of preacinar and intra-acinar arteries in the no-honeymoon group was decreased by reduced external diameter or increased medial thickness. Clinical deterioration in the honeymoon group is based on a vasoconstrictive response of the hypoplastic vascular bed. Persistent hypoxemia in the no-honeymoon group is based on both severity of pulmonary hypoplasia and structural remodeling of the pulmonary arteries. PMID- 4032139 TI - Oral breathing in newborn infants. AB - Newborn infants are considered obligate nasal breathers, hence dependent on a patent nasal airway for ventilation. The conditions under which oral breathing could occur and the contribution of oral ventilation to total ventilation were studied in 30 healthy term infants (aged 1 to 3 days). Nasal and oral airflow were measured using two resistance-matched pneumotachometers, and heart rate, tcPO2, etCO2, and sleep state were continuously recorded. In three of 10 infants studied in undisturbed sleep, spontaneous oronasal breathing was noted during both active and quiet sleep (mean duration 19 +/- 25 minutes), the distribution of tidal volume being 70% +/- 12% nasal and 30% +/- 12% oral. Episodes of oronasal breathing were also observed after crying in six infants (mean duration 21 +/- 19 seconds). In an additional 20 infants, multiple 15-second end expiratory nasal occlusions were performed; eight (40%) of these infants initiated and sustained oral breathing in response to nasal occlusion. Respiratory rate, tidal volume, heart rate, and tcPO2 did not change when oral breathing occurred in response to nasal occlusion, although minute ventilation decreased from 265 to 199 ml/min/kg (P less than 0.05). These results demonstrate that newborn infants may use the oral airway for ventilation, both spontaneously and in response to complete nasal occlusion. PMID- 4032140 TI - Mineral balance during nutritional supplementation in adolescents with Crohn disease and growth failure. AB - The adaptive response of whole body mineral metabolism and collagen turnover to nutritional supplementation was determined in adolescent males with Crohn disease and growth failure. Body calcium, magnesium, phosphorus, and nitrogen status was characterized in six patients before and after 3 weeks of nutritional supplementation and in five healthy age- and sex-matched controls by the metabolic balance technique; collagen turnover was assessed by urinary hydroxyproline excretion. Fecal calcium (P less than 0.05), magnesium (P less than 0.01), and nitrogen (P less than 0.01) losses were significantly greater in the Crohn disease patients compared with the controls; after dietary supplementation, only fecal magnesium excretion increased further (P less than 0.001). Approximately twofold increases in phosphorus (P less than 0.001), nitrogen (P less than 0.02), and calcium (P less than 0.05) retention occurred with nutritional supplementation, whereas the marked renal conservation of phosphorus (P less than 0.001) suggested that this mineral was a limiting nutrient. Urinary hydroxyproline excretion was reduced (P less than 0.05) compared with the control values; however, with nutritional supplementation, urinary hydroxyproline excretion increased significantly (P less than 0.02), suggesting that the soluble fraction of tissue collagen was rapidly turning over during nutritional rehabilitation. These findings suggest that the mineral deficiencies present in adolescents with Crohn disease and growth failure can be reversed with nutritional supplementation. Furthermore, the improvement in nutritional status is reflected in the restoration of collagen-containing tissues of the body. However, nutrient imbalances may be present during nutritional therapy, thereby preventing optimal recovery from malnutrition. PMID- 4032141 TI - Are adolescents able and willing to pay the fee for confidential health care? AB - We studied the ability and willingness of adolescents attending a suburban-based Adolescent Health Service to pay a fee for health care. Self-administered, anonymous questionnaires were distributed to 180 predominantly middle-class adolescent patients prior to the establishment of a fee-for-service payment plan. One hundred sixty-five respondents planned to continue as patients of the Adolescent Health Service; of these, 155 (94%) indicated that they would be able and willing to pay a fee. All of the 155 respondents indicated they could pay $5 per visit, two thirds could pay as much as $10, half could pay $15, and one fifth could pay $20 or more. Sources of fee money would be job earnings, a friend, allowance, and savings; 75% of respondents planned to pay without any help from parents. Analysis revealed few significant correlates of ability and willingness to pay with demographic, socioeconomic, and attitudinal factors. These data demonstrate that, although few of these middle-class adolescent patients indicated that they were able and willing to pay a full fee of $20 or more, most were able and willing to pay more than a token amount for health care. PMID- 4032142 TI - Bloody nipple discharge in infants. PMID- 4032143 TI - Spasmus nutans as a presenting sign of diencephalic syndrome. PMID- 4032144 TI - Lymphoid interstitial pneumonia and rheumatoid arthritis. PMID- 4032145 TI - Hepatic encephalopathy after portacaval shunt. PMID- 4032146 TI - Serotonin and distribution of radiocarbon from D-[14C-U]-glucose in Schistosoma mansoni. AB - Following a 60 min in vitro incubation of Schistosoma mansoni with D-[14C-U] glucose 76% of the radiocarbon was incorporated into metabolic end products and excreted back into the medium. In the presence of 5-HT uptake of glucose increased 61%; excreted end products accounted for 87% of the radiocarbon, indicating increased levels of energy utilization. Substantial amounts of radiolabelled carbon from D-[14C-U-]-glucose were incorporated into glycogen, lipids, amino acids and proteins, suggesting the utilization of glucose carbon in the biosynthetic processes of the parasite. Incorporation of glucose carbon was diminished in the presence of 5-HT, indicating the priority of energy generation over biosynthesis to meet the demands of increased muscular activity. PMID- 4032147 TI - Trypanosoma (Herpetosoma) rangeli Tejera, 1920: mouse model for high, sustained parasitemia. AB - The Neotropical mammalian parasite Trypanosoma (Herpetosoma) rangeli Tejera, 1920 is difficult to study due to the scarcity of blood forms in the vertebrate host. High and persistent parasitemias (up to 7 times the original inoculum at the peak, and persisting for up to 2 wk) were obtained by i.p. inoculation of infant (6.0 g) male white mice (NMRI strain) with 15 X 10(3) trypomastigotes/g body weight from 12-day-old cultures of the "Dog-82" strain of T. rangeli. This strain was cultured 15 mo at ambient temperature in LIT medium, modified by substituting defibrinated adult rabbit blood for fetal calf serum. These results underlined the importance of host age and time of culture of the parasite as factors influencing levels of parasitemia. The abrupt decline in the parasitemias may be due to an early development of a strong immunological response. Negative xenodiagnoses with Rhodnius prolixus may be due either to sterile immunity in the host mice, or to the low susceptibility of the strain of Rhodnius used. Concurrent experiments established that the T. rangeli strain was not naturally contaminated with T. cruzi. PMID- 4032149 TI - Completion of Schistosoma mansoni life cycle in thyroidectomized rats and effects of thyroid hormone replacement therapy. AB - The survival and maturation of Schistosoma mansoni worms was analyzed in normal, thyroidectomized (Thyrox), and hormone-restored Thyrox rats. Restoration therapy was conducted with both T3 and T4; weight gain of treated rats was monitored to assess hormone-replacement efficacy. Worm yields, lengths, and sex-ratios were compared. Egg yields and the capacity of miracidia to hatch from eggs were also analyzed. The results of these studies support the conclusion that the sequence of steps leading to completion of the S. mansoni life cycle are operational in Thyrox rats. Hormone-treated Thyrox rats are restored to the nonpermissive status, although the worms isolated from these rats still differ in certain respects when compared to worms isolated from normal rats. PMID- 4032148 TI - Subcellular fractionation of Hymenolepis diminuta with special reference to the localization of marker enzymes. AB - A method for subcellular fractionation of Hymenolepis diminuta using whole worm homogenization and differential centrifugation is presented. Different fractions obtained in this study were screened for the presence of enzymes that serve as markers for plasma membrane, brush border, mitochondria, Golgi complex, endoplasmic reticulum, peroxisomes, lysosomes and cytosol. The purity of fractions was also monitored by transmission electron microscopy. The purity of fractions, particularly the brush border membranes, are compared to those obtained by previous methods for H. diminuta or other tissues. PMID- 4032150 TI - Taxonomy and distribution of a Crassicauda species (Nematoda: Spirurida) infecting the kidney of the common fin whale (Balaenoptera physalus Linne, 1758). AB - Nematode parasites were found in the kidney of common fin whales (Balaenoptera physalus Linne, 1758) captured in the North Atlantic Ocean (Denmark Strait area). These were identified as Crassicauda boopis Baylis, 1920, on the basis of morphologic and morphometric descriptions of this species' posterior end. The cephalic end of this parasite was described for the first time, however, and was indistinguishable from that of Crassicauda pacifica Margolis and Pike, 1955, a species whose posterior portion is unknown. It was also found that the eggs, size, host, and site of infection of both C. boopis and C. pacifica are indistinguishable. This established the synonymy of C. boopis with the more recently named taxon, C. pacifica. In light of previous descriptions of Crassicauda infections in balaenopterids, this implied that C. boopis should at present be considered a renal parasite of fin whales, and perhaps other rorquals, throughout the world's oceans. PMID- 4032151 TI - In vitro development of Strongylus edentatus to the fourth larval stage with notes on Strongylus vulgaris and Strongylus equinus. AB - Strongylus edentatus was successfully cultured in vitro to the fourth larval stage (L4). Some growth continued for periods of 40-50 days at which time reductions in viability were observed in some of the culture systems tested. Various combinations of media, sera, buffers and organ explant cultures were tested. All cultures were incubated at 37 C in an atmosphere of 95% air and 5% CO2. Larvae underwent growth and differentiation to the L4 in all medium-serum combinations with and without organ explant cultures. Development and growth did occur but viability was reduced to insignificant levels in media without serum or cells. Optimal growth, differentiation, and longevity were observed in bicarbonate buffered RPMI-1640 containing 10% fetal calf serum and gerbil (Meriones unguiculatus) cecum explant cultures. Observations indicated that Strongylus vulgaris and Strongylus equinus also developed to the L4 stage using similar techniques. However, viability of S. vulgaris L4 was markedly limited. Specific morphological changes marked phases of development of S. edentatus, categorized as early, middle and late third stage, third molt and early fourth stage. Strongylus equinus appeared to follow the same developmental pattern in vitro as S. edentatus. Distinct differences in morphological features during differentiation were observed between S. edentatus and S. vulgaris. PMID- 4032152 TI - The spermatogenesis of Dictyocaulus filaria (Nematoda, Trichostrongyloidea). AB - A cytological study was carried out, using male Dictyocaulus filaria, that revealed the diploid number of chromosomes was 2n = 11 and the sex determining mechanism was XO. The behaviour of the chromosomes in the different stages of meiosis was also investigated. Cross, open ring and rod bivalents were observed in diakinesis. The chromosomes appeared to be acrocentric since they acquired a radial disposition in Metaphase-II. The chiasma frequency was 1 and the nucleolus organizing region was located at the ends of the chromosomes. PMID- 4032153 TI - Prevalence of Setaria equina (Nematode: Onchocercidae) in southeastern Louisiana horses. PMID- 4032154 TI - Relationship between skin-sensitizing antibody production in the snowshoe hare, Lepus americanus, and infestations by the rabbit tick, Haemaphysalis leporispalustris (Acari: Ixodidae). PMID- 4032155 TI - Immunization with purified antigens protects mice from lethal infection with Trichinella spiralis. PMID- 4032156 TI - The life cycle of Schistosoma mansoni under germ free conditions. PMID- 4032157 TI - Compliance issues in 1985. PMID- 4032158 TI - Structure of products prepared by freeze-drying solutions containing organic solvents. PMID- 4032159 TI - Vertical transmission of HBV hepatitis to fetuses and infants: current advances in prevention. PMID- 4032160 TI - Specificity of human milk bile salt-stimulated lipase. PMID- 4032161 TI - Intestinal permeability. PMID- 4032162 TI - Prevention of perinatally transmitted hepatitis B virus infection by hepatitis B immunoglobulin immunoprophylaxis: an account of 201 newborn babies of hepatitis Bs antigen carrier mothers. AB - Of 5,327 pregnant women who were screened between July 1981 and July 1983, 5.2% were found to be hepatitis Bs antigen (HBsAg) carriers. This high percentage of carriers accentuates the importance of vertical transmission of hepatitis B virus in our area. In view of this we sought to verify the effectiveness of hyperimmune immunoglobulins in the prevention of infection. We studied 201 babies born to HBsAg-positive mothers. These babies had regular checkups until 12 months of age. One hundred forty-nine received prophylactic hyperimmune globulin (two to seven doses according to risk ranking), while 52 did not. A higher percentage of infection was found in the babies who had no prophylaxis (25%) than in the babies who had prophylaxis (7.4%). Furthermore, hepatitis appeared earlier (from the 2nd to the 6th month) in the babies who had no prophylaxis than in the babies who had prophylaxis (from the 9th to the 12th month). No infection was observed during prophylaxis or up to 6 months. PMID- 4032163 TI - Elevated serum gamma-aminobutyric acid levels in children with Reye's syndrome. AB - Elevated serum levels of gamma-aminobutyric acid (GABA), a potent inhibitory neurotransmitter, have recently been implicated in the pathogenesis of hepatic encephalopathy. In this study, serum GABA levels were measured in five children with severe Reye's syndrome, 10 children with acute viral hepatitis, and seven healthy volunteers. Serum GABA levels were highest in the five Reye's syndrome patients. The mean serum GABA level for the Reye's syndrome group (3.0 +/- 1.3 microM, mean +/- SEM) was significantly elevated as compared to the mean of the viral hepatitis group (0.72 +/- 0.07 microM, p less than 0.05) and the healthy volunteers (0.38 +/- 0.04 microM, p less than 0.05). These results provide preliminary evidence to suggest that elevated serum GABA levels may in part be responsible for the encephalopathic state observed in children with Reye's syndrome. PMID- 4032164 TI - Platelet-monoamine oxidase activity in Reye's syndrome. AB - Platelet and liver monoamine oxidase (MAO) activity (mean +/- SD) was evaluated in patients with liver-biopsy-proven Reye's syndrome. MAO was measured by a radioenzymatic technique with [3H]tyramine as a substrate. A marked decrease in MAO activity [3.3 +/- 2.4 nmol of [3H]4-hydroxyphenylacetic acid formed X (mg protein)-1 X h-1] was observed in platelets on admission in all patients (n = 13) with Reye's syndrome when compared with hospitalized patients without liver disease (n = 8) [9.8 +/- 2.5 nmol of [3H]4-hydroxyphenylacetic acid formed X (mg protein)-1 X h-1] and with liver disease (n = 10) [9.1 +/- 2.0 nmol of [3H]4 hydroxyphenylacetic acid formed X (mg protein)-1 X h-1]. Following recovery from the disease, platelet MAO approached levels that were not significantly different from those of controls. Contrastingly, reduction of hepatic MAO in Reye's syndrome was similar to that seen in patients with liver disease of different etiologies. These studies suggest that reduced platelet MAO activity is a specific abnormality in Reye's syndrome, and it may be representative of generalized impairment of mitochondrial function in these patients. Furthermore, the pattern of liver and platelet MAO activity in Reye's syndrome may allow for the differentiation of this disease from other hepatopathologic conditions. PMID- 4032165 TI - Intrahepatic biliary tract abnormalities in children with corrected extrahepatic biliary atresia. AB - Three children with surgically corrected extrahepatic biliary atresia developed recurrent cholangitis associated with bile lakes that failed to drain via the hepatoportoenterostomy. Surgical or percutaneous drainage of these cysts was followed by both resolution of the infection and spontaneous internal drainage. We postulate that the ongoing inflammatory process resulted in intrahepatic biliary obstruction, which caused cholangitis and bile cysts. Successful treatment required not only antibiotics but drainage of the bile lakes. Development of bile cysts is a new cause of recurrent cholangitis seen in extrahepatic biliary atresia. PMID- 4032167 TI - Rumination syndrome in children treated by increased holding. AB - Rumination syndrome--the frequent regurgitation of previously ingested food into the mouth where it is chewed--is a common, life-threatening disorder of retarded individuals. Four cases are described in which holding a retarded, ruminating child for 10-15 min before, during, and after meals, was associated with remission of rumination. Simple holding was effective in three; in the fourth, it was necessary to punish the child by putting her into a separate room for 3 min immediately after regurgitation. A within-subject reversal experimental design suggested that holding and not simple distraction was the effective component of the treatment. Treatment benefits were well maintained when the child returned to a home environment in which he or she continued to be held periodically. It is proposed that there are two behavioral etiologies for idiopathic rumination syndrome--social deprivation and reward learning through increased attention for regurgitation. Holding is the treatment of choice for the first type, and punishment with time out may be necessary to suppress regurgitation in the second type. PMID- 4032166 TI - Erythrocyte lipid alterations in pediatric cholestatic liver disease: spur cell anemia of infancy. AB - Spur cell anemia of liver disease is a hemolytic process characterized by spiculated erythrocytes and an elevated red cell membrane cholesterol/phospholipid (C/PL) molar ratio. This form of anemia is associated almost exclusively with adults in the advanced stages of alcoholic cirrhosis. We were therefore surprised to identify two unrelated infants with cholestatic liver disease and hemolytic anemia who had spiculated erythrocytes as the major abnormal cell form on peripheral smear. Erythrocyte membrane cholesterol and phospholipid determinations from these patients were compared with six infants with extrahepatic biliary atresia and target-shaped erythrocytes and with five normal adults. Erythrocyte C/PL molar ratio distinguished target cells from normal erythrocytes (p less than 0.01). The spur cell patients' erythrocyte C/PL molar ratios were clearly greater than either target cell patients or normal controls (1.30 vs. 1.02 vs. 0.84). Both patients' spur cell anemia resolved and target cells became the major abnormal erythrocyte form. These studies identify a transient form of spur cell anemia associated with infantile cholestatic liver disease. The factors leading to the formation of spur cell anemia in infancy require further investigation. PMID- 4032168 TI - Esophageal stricture dilatation in awake children. AB - Dilatation of esophageal strictures in children has generally been performed in the hospital under general anesthesia, or under deep sedation. We report here a series of 211 dilatations in 13 pediatric patients who had these procedures performed in the outpatient department, 72% of them without any sedation, during a 4-year period. This report characterizes the children, the method of outpatient dilatation, and our results. At the end of the study period, six of the patients no longer required dilatation after five to 14 procedures; four patients still required dilatation at twice-yearly intervals; and three patients remained on an active schedule of dilatations at intervals less than 5 months. Esophageal lumen diameter increased and symptoms improved in all of the children. Catch-up weight gain occurred in one-half of those initially below the 10th percentile. Dilatation without anesthesia or sedation was preferred by all of the parents, and by those children old enough to express a preference. Estimated reduction of medical costs by more than $100,000 was realized, compared with bouginage using general anesthesia. No episode of perforation, significant hemorrhage, documentable aspiration, or neurologic complication occurred. Outpatient dilatation without anesthesia is an effective method of treating esophageal strictures in children. PMID- 4032169 TI - Differential effect of botulinal toxin on esophageal motor function in infants. AB - The effect of Clostridium botulinum toxin on esophageal motor function was studied in four infants (ages 5-9 months) with confirmed infant botulism. Esophageal motility studies using a perfused catheter assembly were performed during the acute phase in all patients, and during the recovery phase in one patient. Motor function of the proximal esophagus and upper esophageal sphincter was abnormal in each, while motor function of the distal esophagus and lower esophageal sphincter was normal. Mean lower esophageal sphincter pressure was 24 mm Hg for the group (normal: 15-30 mm Hg). Sequential studies of proximal esophageal motility in one infant revealed a return of normal motor function which correlated with recovery of peripheral muscle strength and gag reflexes. C. botulinum toxin impairs proximal, but not distal, esophageal motor function in the infant botulism model. This effect appears to be consistent with the known action of the toxin on synaptic acetylcholine release and current concepts regarding distribution of cholinergic and noncholinergic neurotransmitter receptors in the esophagus. PMID- 4032170 TI - Intestinal sugar permeability: relationship to diarrhoeal disease and small bowel morphology. AB - The permeability of the intestine was studied in 39 children (1 month to 3 years of age) with diarrhoea and in 28 children (6 months to 15 years of age) undergoing duodenal biopsy. Permeability was measured by differential absorption from an isotonic oral load containing 3.5 g lactulose, 0.5 g L-rhamnose, 0.5 g D xylose, and 5 g lactose. Urinary sugar excretion was determined by quantitative thin-layer chromatography. Children with acute gastroenteritis had a greatly increased permeability, with a mean lactulose/L-rhamnose excretion ratio of 0.43 +/- 0.31 (normal less than 0.07). Children retested 3-16 weeks after complete recovery of their gastroenteritis had normal permeability (0.045 +/- 0.018). Children with chronic diarrhoea also had an increased permeability (0.12 +/- 0.074), but significantly less than the acute gastroenteritis group (p less than 0.01). Abnormal proximal small bowel morphology was associated with increased permeability, and a strong correlation between crypt depth and permeability was observed (r = 0.66, p less than 0.001). Abnormal intestinal permeability was associated with diarrhoeal disease and with mucosal damage. It appears to be a reliable and useful index of mucosal integrity. PMID- 4032171 TI - The development of methane production in childhood and adolescence. AB - Methane concentration in the expired air was analyzed in 393 infants, children, and adolescents. There was no methane production below the age of 3 years. In the age group 3-4 years, 6.4% of the children produced methane. The percentages were 14.3-18.2% in children aged 7-14. A rise in methane production to 39.4-45.9% was recorded from age 14 to 18, as compared with 49.4% in adults in Israel. The reasons for these changes in methane production with age are not known. Alterations in the colonic flora or the production of a specific substrate(s) are the main possibilities. In our opinion, the latter possibility deserves further investigation. PMID- 4032172 TI - Specificity of human milk bile salt-stimulated lipase. AB - A crude preparation of the bile salt-stimulated lipase in human milk did not differentiate between the primary and secondary esters of several synthetic triacylglycerols. The dioleoyl ester of 2,3-butanediol was also digested, unequivocal confirmation of the absence of positional specificity. Preferential release of 18:2 relative to 16:0 and 18:1 as compared to 18:1t (trans) was observed. The lipase did not differentiate between 16:0 and 18:1 or 16:0 and 18:0. PMID- 4032173 TI - Relationships between lysozyme concentration of human milk, bacteriologic content, and weight gain of premature infants. AB - Lysozyme concentrations and bacterial colony counts were determined in 399 human milk samples obtained from 42 mothers (18 mothers of term infants, 24 mothers of preterm or small-for-date neonates). The average lysozyme concentration was 21.39 +/- 13.19 mg/L. Lysozyme concentrations were significantly greater in preterm (24.99 +/- 15.05 mg/L) than in term milk (14.89 +/- 9.83 mg/L) (p less than 0.05). Bacterial colony counts did not decline with increasing lysozyme concentration, i.e., no correlation between lysozyme concentration and bacterial count was found. Despite this lack of correlation, a significant correlation between lysozyme concentration and rate of weight gain was observed: the higher the lysozyme concentration, the better the weight gain. The mechanism of this observation remains to be elucidated; a trophic effect of lysozyme is suggested as a possible mechanism. PMID- 4032174 TI - Human milk lipase substrates: electronic role. AB - The hydrolysis of a series of 4'-nitrophenyl 4-substituted benzoates, catalyzed by human milk lipase in the absence and presence of cholate stimulation, has been measured at pH 7.3, 37.5 degrees C. There is no evidence for an acyl site electronic interaction in the rate determining step of the esterolytic reaction. Substrate inhibition, arising from restricted rotation of the aryl residues about the ester linkage in the esterolytic site, is exhibited by these substrates. PMID- 4032175 TI - Anorectal manometry for the exclusion of Hirschsprung's disease in neonates. AB - We studied the usefulness of anorectal manometry in excluding Hirschsprung's disease in 25 neonates with signs and symptoms of intestinal obstruction. An intraluminal pressure transducer or perfused side-opening catheters were used to evaluate anal tone, anal rhythmicity, and internal sphincter relaxation during rectal distention. Hirschsprung's disease was diagnosed by rectal biopsy in 16% of the neonates. Studies using anorectal manometry gave one false positive and one false negative diagnosis of Hirschsprung's disease, which resulted in 75% sensitivity, 95% specificity, and a kappa coefficient of 0.7. We found that anorectal manometry, a rapid and atraumatic test, is a reliable screening test for exclusion of neonatal Hirschsprung's disease. By using the combination of manometry and contrast enema, it is possible to eliminate the need for a confirmatory rectal biopsy in many neonates suspected of having Hirschsprung's disease. PMID- 4032176 TI - Early intravenous correction of vitamin E deficiency in premature infants. AB - We undertook to determine the efficacy of intravenous alpha-tocopheryl acetate in rapidly correcting the vitamin E deficiency of the premature infant. Twenty-nine infants were assigned to either a control or treatment group. The latter group received a median intravenous dose of 3 IU/kg/day alpha-tocopheryl acetate as MVI 12 (USV Pharmaceuticals, Inc.). On days 1, 2, 3, 7, 14, and 21, plasma tocopherol isomers and peroxide-induced hemolysis were analyzed. While all but one control infant with initial tocopherol deficiency were still deficient on day 3, all but two of the treatment infants were normal. Rapid, safe correction is possible with an intravenous multivitamin preparation. PMID- 4032177 TI - Zinc, copper, manganese, and selenium metabolism in patients with human growth hormone deficiency or acromegaly. AB - This study was designed to evaluate trace metal metabolism in patients with known abnormalities of human growth hormone (hGH). The mean concentration of zinc in plasma and urine decreased in patients with hGH deficiency after hGH injection, whereas, after adenomectomy, in patients with acromegaly, zinc increased in plasma, remained the same in erythrocytes, and decreased in urine. There was a negative correlation between plasma zinc and serum hGH levels and a positive correlation between urinary zinc excretion and serum hGH levels in acromegaly. In hGH deficiency, the copper content remained unchanged in plasma and erythrocytes and rose in urine after treatment; however, in acromegaly, the copper content increased in plasma and remained unchanged in erythrocytes and urine after surgery. The mean concentration of erythrocyte manganese did not change significantly after treatment in patients with hGH deficiency or acromegaly, but the pre-hGH treatment level of erythrocyte manganese in hGH deficiency was lower than in the controls. Plasma selenium concentrations were decreased in hGH deficiency and increased in acromegaly patients after therapy. These results suggest that hGH affects the metabolism of zinc, copper, manganese, and selenium. PMID- 4032178 TI - Consequences of complete bile-duct ligation on the pubertal process in the male rat. AB - Prepubertal male rats underwent bile-duct ligation or a sham operation. Sham operated animals were divided into two groups: isocalorically-fed (matched to the bile-duct-ligated animals) and ad-libitum-fed animals. At 60 days of age (after puberty in a male rat) all animals were killed. Bile-duct-ligated animals had larger livers, greater bilirubin, greater bile acid, greater aspartate transaminase, and greater alkaline phosphatase levels and lower testosterone and luteinizing hormone levels in their serum than did the controls. Moreover, the testes and seminal vesicles were smaller in the bile-duct-ligated animals than in the controls. These data suggest that chronic cholestasis contributes, at least in part, to the pubertal and maturational failure that occurs with the chronic cholestatic diseases of childhood. PMID- 4032179 TI - Precocious increase of sucrase activity by carbohydrates in the small intestine of suckling rats. II. Role of digestibility of sugars, osmolality, and stomach evacuation in producing diarrhea. AB - The mechanisms of carbohydrate-induced diarrhea in suckling rats were investigated with respect to osmolality and type of sugar in the milk. Groups of 12-day-old rats were gavage fed either a basic low carbohydrate milk formula [10.8% fat; 8% protein; 1.4% carbohydrate (weight/volume)] or basic formula with added sucrose, fructose, lactose, or glucose polymers, all as 13% (weight/ volume). All formulas were isocaloric. Their corresponding osmolalities were 278, 645, 1,130, 617, and 349 mOsmol/kg, respectively. Gastric evacuation of water soluble materials from formulas containing sucrose, fructose, or glucose polymers was significantly slower than the gastric evacuation of the basic formula and the formula that contained lactose. The net fluid absorption from the small intestine was significantly greater from the basic and lactose-containing formulas when compared with sucrose, fructose, or glucose polymer-containing formulas. When the synthetic milk formulas were placed directly into the isolated jejunoileum in vivo, the formulas of higher osmolality (fructose, sucrose, and lactose) caused water flux into the intestine at 60 min, while digestion of the lactose formula reversed the water flux within 120 min. We conclude that the type of added sugar is a decisive factor in gastric evacuation, and that water flux into and out of the intestine is significantly affected by the osmolality and rate of digestion and absorption of the carbohydrate in the formula; these differences among sugars may play a significant role in the etiology of diarrhea. PMID- 4032180 TI - Life-saving immunosuppressive treatment in severe autoimmune chronic active hepatitis. AB - A 13-year-old girl with a 1-year history of elevated serum alanine transferase was hospitalized because of liver failure. Low prothrombin time (12%) prevented needle liver biopsy. Because of a high titer of antismooth-muscle antibodies (1:500), a tentative diagnosis of "autoimmune" chronic active hepatitis was made and immunosuppressive therapy was started. Despite the severity of the liver disease, of her poor general condition, and of spontaneous bacterial peritonitis, she dramatically responded to treatment, prothrombin time returning to normal within 5 months. Diagnosis of chronic active hepatitis was later confirmed by liver biopsy. This report indicates that immuno-suppressive therapy can be life saving in children with severe chronic active hepatitis even when major signs of liver failure are present. PMID- 4032181 TI - Thrombosis as a complication of inflammatory bowel disease in children: a report of four cases. AB - Thrombosis and thromboembolism have rarely been reported in inflammatory bowel disease (IBD) in children. Four cases of thrombosis, two with apparently serious thromboembolism, are reported in three patients with ulcerative colitis and one with Crohn's disease. Two patients were on steroid treatment at the time of the initial thromboembolic event. Thrombosis may result from a "hypercoagulable state" that occurs in IBD, brought about by a combination of altered clotting factors and the presence of a thrombogenic gastrointestinal mucosa, the risk of which is increased by steroid medications. Children and adolescents with IBD are at risk for serious thromboembolic complications. PMID- 4032182 TI - Long-term monitoring of D-lactic acidosis in a child. AB - A case of D-lactic acidosis in a 2 1/2-year-old child followed for 11 months is reported. The infant had previously undergone extensive small intestinal resection for midgut volvulus. Diagnosis was confirmed by measurement of plasma D lactate. Metabolic acidosis, increased anion gap, ataxia, and lethargy in patients with small intestinal resection warrant investigation for D-lactic acidosis. The presumed etiology is absorption of D-lactic acid produced by bacterial fermentation of carbohydrate in the colon. Antibiotic treatment resulted in prompt resolution of symptoms in this case. Prospective and prolonged monitoring of acidosis in patients with small bowel resection is encouraged. PMID- 4032184 TI - Bacterial overgrowth. PMID- 4032183 TI - Copper deficiency in infants with active celiac disease. AB - Celiac disease was diagnosed in two unrelated infants aged 7 and 7.5 months with severe malnutrition. They showed typical clinical, biological, and histological signs of the disease. Moreover, accompanying copper deficiency was suggested by severe hypocupremia and persistent neutropenia; bone radiographs were also compatible with this diagnosis. Rapid and complete correction of these anomalies could only be obtained after addition of oral copper sulfate to the gluten-free diet. Mechanisms possibly involved in the development of copper deficiency in young infants with celiac disease are: chronic malabsorption; high copper needs in rapidly growing infants; and possibly increased biliary and digestive losses. It is therefore suggested that young children with severe celiac disease should be monitored for their copper status. PMID- 4032185 TI - Ultrastructural study of alterations in the small intestinal epithelium of children with acute diarrhoea. PMID- 4032186 TI - Congenital eyelid eversion with orbicularis spasm. AB - Eversion of the lids at birth is a rare condition of debated etiology. It has been attributed most frequently to birth trauma or to congenital lid hypotonia. Most reported cases have been treated by immediate taping of the lids or by surgery (tarsorraphy, intermarginal sutures, and/or plastic procedures). A prominent association with Down's syndrome has been noted. We report a normal infant, born by Caesarean section, with bilateral upper eyelid eversion which subsided spontaneously after treatment only with lubricants. A prominent spastic ectropion component was observed. Lid laxity appeared to be an effect rather than a cause of the eversion, and disappeared as the condition improved. Management should take into account the duration of total occlusion caused by this abnormality. PMID- 4032188 TI - Unilateral traumatic aphakia in children: role of corneal contact lenses. AB - Twenty-eight children below ten years of age with unilateral traumatic aphakia were fitted with hard corneal contact lenses. Visual acuity of 6/12 or better was achieved in 68% of the cases. Patients who were above seven years of age at the time of injury, and those fitted with contact lenses within eight months of trauma, were found to have better chances of recovering normal binocular functions. PMID- 4032187 TI - Weill-Marchesani syndrome with bilateral angle-closure glaucoma. AB - To our knowledge this is the first reported case of cyclopentolate induced bilateral acute angle-closure glaucoma associated with the Weill-Marchesani syndrome without lens subluxation. The diagnosis of Weill-Marchesani syndrome was not initially suspected, and Pilocarpine was used in an attempt to break the acute attack. Treatment with Pilocarpine-induced myosis only worsened the glaucoma by causing a severe pupillary block. This case is important because it demonstrates that mid-dilatation and cycloplegia can induce acute glaucoma in patients with the Weill-Marchesani syndrome and points out the importance for considering the diagnosis of Weill-Marchesani syndrome in any case of acute glaucoma in childhood. PMID- 4032189 TI - Normal saccadic velocity study. PMID- 4032190 TI - Traumatic inferior oblique muscle paresis. PMID- 4032191 TI - Combined congenital glaucoma, pigmentary glaucoma, and high myopia in an infant. AB - A case of congenital glaucoma combined with pigmentary glaucoma and high myopia in a three-month-old infant is described. The pathophysiology, medical treatment, and review of the literature is discussed. PMID- 4032192 TI - Glycoconjugates, cellular differentiation, and congenital glaucoma. AB - Studies of congenital glaucoma have described and debated the disease process in cellular and structural terms, yet the functional aspects of the disease remain poorly understood. This paper presents an attempt to look at the disease from a different perspective: the role of glycoconjugates and their influence on morphogenesis of the corneoscleral angle. Extracellular and cell-surface complex carbohydrates and trabecular meshwork development were observed in normal C-57 BL/6J mice with light and electron microscopy. Lectin-stained fixed tissues were evaluated by fluorescein light microscopy and with computer-controlled scanning microspectrophotometry. The appearance and type of specific glycoconjugates was related to morphogenesis and differentiation, with specific reference to the development of the trabecular meshwork. Our results suggest that glycoconjugates are: (1) important in the morphogenesis of the corneoscleral angle, and (2) provide some of the required signals for the differentiation of the cells of the trabecular meshwork. These findings emphasize the possibility that a complex series of morphological and biological events in the normal development of the trabecular meshwork ultimately leads to a functionally competent trabecular meshwork, that is, capacitation. PMID- 4032193 TI - Modern strategy for the term breech delivery--a study with a 4-year follow-up of the infants. AB - In a comprehensive 4-year follow-up study the long-term outcomes in 709 singleton term breech born infants were evaluated. The outcome has been related to different management protocols during two consecutive study periods. In the first period (A, 1971-1974) the rate of cesarean section was 16.1% and in the second period (B, 1974-1977) 37.1%. The neonatal mortality rate was the same in both study periods (0.3%). The incidence of long-term neurodevelopmental handicaps was in period A 5.3% and in period B 2.4% at 4 years of age. Sequelae among infants in period A were in most cases labor-related, i.e. footling, extended arms or difficulty in descent of the fetal head. An antero-posterior diameter of less than 12 cm at the brim was common in these cases. In both study periods there was an increased risk of neurodevelopmental handicaps for infants with hyperextension of the head in the breech position delivered by the vaginal route. In period B the incidence of neurodevelopmental sequelae at the 4-year follow-up did not differ from that found in a group of infants born vaginally in vertex presentation. The rates of visual and auditory disorders, behaviour problems, enuresis and late speech development were not increased in the breeches neither in period A nor in period B. PMID- 4032194 TI - Assessment of gestational age: a simplified scoring system. AB - Because of the disadvantages of the Dubowitz score in very ill preterms, an alternative score based on 7 morphological items was designed, and the results are compared to those of the Dubowitz score in 229 newborns. This scoring system proved to be reliable and easy to perform; standard deviation was +/- 10.2 days versus 9.7 days for the Dubowitz score. PMID- 4032195 TI - Plasma creatinine in neonates with atresia of the upper gastrointestinal tract. AB - The human fetus swallows a considerable amount of amniotic fluid which appears to be in balance with the urine output. Since amniotic fluid intake is considered to be compromised in fetuses with atresia of the upper gastrointestinal tract, glomerular function development in such infants may be delayed. Plasma creatinine level determined in 6 neonates with atresia of the upper gastrointestinal tract was similar to the level measured in neonates with lower obstruction, and both groups were within the range of values obtained during other studies in normal newborns. Glomerular functional development is probably not affected in neonates with atresia of the upper gastrointestinal tract. PMID- 4032196 TI - Cholesterol synthesizing enzymes in term human fetal amnion. AB - Based on the observations that human fetal membranes possess the ability to synthesize steroid hormones, we sought to investigate the precursor role of 2 - 14C acetate in cholesterol formation by term human fetal amnion. Concentrations of derivatized 14C cholesterol was measured by reverse-isotope dilution technique in incubations of 2 - 14C acetate with homogenates of term fetal amnion dissected from 5 human placentae (37-40 weeks gestation) delivered vaginally from uncomplicated pregnancies (age 22-29 years). Controls consisted of homogenates heated in a boiling water bath for 10 min. The data presented demonstrate incorporation of 2-14C acetate into 14C cholesterol by the viable tissue. The extent of enzymic conversion varied from 0.002% to 0.076%. The small but definite conversion indicates that the homogenates of term human fetal amnion contain the full complement of enzymes necessary to catalyse the transformation of acetate to cholesterol. The metabolic need for cholesterol supply during labor is discussed. PMID- 4032197 TI - Nonimmunologic hydrops fetalis: a review of 11 cases. AB - Eleven cases of nonimmunologic hydrops fetalis occurring during a six year period were reviewed. The etiology of hydrops fetalis was established only in four cases. It included one case of endocardial fibrosis, two cases of non-immunologic hemolysis and one case of tachycardia. The pregnancies were complicated by polyhydramnios in 9 cases, preterm delivery in 10 cases, twins in 3 cases and pre eclampsia in one case. Four of 11 fetuses died in utero, on one of them, intrauterine blood transfusion and administration of digoxin and furosemide was carried out. Five fetuses died neonatally and two survived. In one of the later cases, intravenous administration of digoxin with quinidine to the mother was without effect, nor did such treatment cause any effect on the neonate after delivery. Electric cardioversion supplemented with digoxin slowed the neonatal cardiac rhythm to normal range with later successful outcome. Earlier diagnosis by ultrasonography especially in cases of hydramnios and appropriate treatment are likely to improve this outcome. PMID- 4032198 TI - MCMI characteristics of DSM-III posttraumatic stress disorder in Vietnam veterans. AB - Compared the MCMI profiles of 25 veterans with a diagnosis of Posttraumatic Stress Disorder (PTSD) with those of 25 veterans carrying psychiatric disorders which typically cause problems in the differential diagnosis of PTSD. The PTSD group had higher elevations on nine of the 20 MCMI scales (all ps less than .05). Profiles were also significantly different in shape and scatter. A discriminant analysis accounted for 100% of the variance and correctly classified 88% of the patients. Resulting MCMI profiles appear to be consistent with DSM-III criteria for PTSD. PMID- 4032199 TI - Stability of the personality and symptom scales of the Millon Clinical Multiaxial Inventory. AB - This study examines the stability of the basic and pathological personality and symptom scales of the Millon Clinical Multiaxial Inventory (MCMI) in three clinical samples. Consistent with the theory upon which the MCMI is based, higher stability estimates were found among basic personality scales in comparison with symptom scales. However, stability estimates which included initial MCMI administrations at intake into treatment were generally lower than those based upon administrations which occurred later in the treatment process. This later finding suggests the need to consider timing of administration when interpreting the MCMI. PMID- 4032200 TI - Aggressive response sets and subtle-obvious MMPI scale distinctions in male offenders. AB - The effects of aggressive and nonaggressive response sets on the MMPI subtle and obvious clinical subscales were investigated. Fifty-eight male prison inmates answered the MMPI as if they were either highly aggressive or highly nonaggressive. The clinical scales with sufficient items in each category were scored for subtle, neutral, and obvious subscales. Inmates successfully feigned aggressiveness on several of the obvious subscales (p = .0056) and one neutral scale; the subtle subscales were not significantly different across groups, consistent with previous research on this population in terms of the resistance of subtle items to these response sets. PMID- 4032201 TI - The development and cross-validation of an MMPI typology of murderers. AB - A sample of 80 male offenders charged with premeditated murder were divided into five personality types using MMPI scores. A hierarchical clustering procedure was used with a subsequent internal cross-validation analysis using a second sample of 80 premeditated murderers. A Discriminant Analysis resulted in a 96.25% correct classification of subjects from the second sample into the five types. Clinical data from a mental status interview schedule supported the external validity of these types. There were significant differences among the five types in hallucinations, disorientation, hostility, depression, and paranoid thinking. Both similarities and differences of the present typology with prior research was discussed. Additional research questions were suggested. PMID- 4032202 TI - MMPI scales for DSM-III personality disorders: their derivation and correlates. AB - Scales tapping the dimensions of personality disorder as represented in the DSM III were derived using a combined rational/empirical strategy. The final version of the scales demonstrated both content validity as well as internal consistency. Correlations between the derived scales and between these scales and the original MMPI clinical scales were generally found to be in the expected direction providing preliminary evidence of criterion related validity. It is suggested that the derived scales may represent an advance toward the reliable assessment of DSM-III personality constructs. PMID- 4032203 TI - Clinical correlates of high lie scale elevations among forensic patients. AB - The MMPI Lie scale serves as an indicator of test validity, primarily intended to detect efforts by psychologically unsophisticated subjects to present themselves in an unrealistically positive fashion. The unexpected occurrence of Lie scale elevations among paranoid patients not considered to be unsophisticated or naive prompted previous researchers to speculate that the measure might have other interpretive utility. The current study examined the potential relationship between high Lie scores and paranoid psychopathology in a forensic population. All subjects who met the inclusion criteria, Lie greater than raw score of six and no clinical scale elevations, were found to have some type of psychotic disorder with prominent paranoid features. The possible implications of the findings for clinicians responsible for determinations of dangerousness resulting from mental illness were discussed. PMID- 4032204 TI - The Mezzich MMPI regression formula revisited. AB - In a sample of depressed psychiatric inpatients, the Mezzich regression formula, based on five MMPI scales, correlated moderately with clinicians' judgments and yielded few false negative diagnoses in identifying patients with unipolar Major Depressive Disorder, but was less effective in eliminating false positives. PMID- 4032206 TI - Renal failure adjustment and coping style. AB - The role of coping style in renal failure adjustment was investigated in a sample of 62 patient volunteers. Two descriptive questions were considered. Is psychosocial adjustment related to coping style? Do patients receiving differing treatments rely on distinctive coping styles? Aggressive coping style was inversely related to psychological adjustment. Patients receiving staff supervised treatment had significantly higher scores on a scale measuring more passive defense. PMID- 4032205 TI - Ego development and intelligence in a psychiatric population: Wechsler subtest scores. AB - The relationship between Loevinger's measure of ego development and the Wechsler Intelligence Scales subtest scores was investigated in 91 adolescent and young adult psychiatric inpatients. Correlations with Verbal IQ and verbal subtests in general were positive and significant. The correlation with the Comprehension subtest was the highest and remained significant when Full Scale IQ was partialled. Post-conformists obtained the highest mean scores on Picture Arrangement; however, there was no difference among the lower stages on this subtest. The results lend support to a social reasoning component of ego development. PMID- 4032207 TI - Understanding multiple personality with the Comprehensive Rorschach system. AB - Exner's Comprehensive Rorschach system is utilized in studying a unique sample of patients--three multiple personalities. Each patient and a number of secondary personalities are tested. Several interpretative and technical aspects of Exner's system are clarified. All of the main personalities are ambient, extending Exner's conclusions regarding the implications of this style. The secondary personalities have personality structures which are remarkably different from those of the main personalities. Differences from previous studies are attributed to unique administrative features of the Comprehensive system. PMID- 4032208 TI - Schizophrenic, depressive, and nonpatient personality organizations described by Rorschach factor structures. AB - Rorschachs of 155 schizophrenics, 102 depressives, and 186 nonpatients were collected and scored using the Comprehensive System. Twenty-seven Rorschach variables considered central to interpretation were selected for study. Factor analyses and partial correlations controlling for number of responses, R, were generated in order to investigate the personality organization of each of the three groups. A three factor solution was found to be optimal for each group. Patterns of personality organization were discussed within the three groups and factor structures were compared and contrasted. While similarities occur between the three groups, each group also manifests a unique personality organization. These findings support the hypothesis that schizophrenics and depressives differ from nonpatients in kind, rather than degree of disorder. PMID- 4032209 TI - Content analysis scales measuring psychosocial maturity in the elderly. AB - Content analysis scales measuring the constructs used to deal with the tasks of Erikson's eight stages of psychosocial development have been devised. The scoring categories for these 16 Content Analysis Scales of Psychosocial Maturity (CASPM) are summarized. Percentile norms are provided. Evidence for the reliability and validity of the scales is examined. The CASPM percentile profiles of two elderly people are considered, as are the practical advantages of employing the scales with elderly clients. PMID- 4032210 TI - [Analytic study of piroxicam]. PMID- 4032211 TI - [Furocoumarins in essential oils. Identification and determination of 5 methoxypsoralen in sun products]. PMID- 4032212 TI - [Clometacin. 5. Pharmacokinetic study of a fast-acting form in man]. PMID- 4032213 TI - [Study of the desorption of ethylene oxide from different plastic materials sterilized by the gas]. PMID- 4032214 TI - Determination by high performance liquid chromatography of the stability of alcoholic solutions for topical use containing tetracycline and 4 epitetracycline. PMID- 4032215 TI - Spectrophotometric determination of catecholamines. PMID- 4032216 TI - Effect of water immersion stress on the biosynthesis of rat gastric glycoproteins with or without sulfate. AB - The biosynthesis of rat gastric glycoproteins with or without sulfate was investigated in rats subjected to restraint and water immersion stress. Studies were carried out in vitro in rat glandular stomach using 3H-glucosamine and 35S sulfate. Labeled glycoproteins were extracted with 2% Triton X-100 and fractionated on Bio Gel A-1.5 m. Radioactivity incorporated into glycoproteins was estimated in the tissue as well as in the medium. The incorporation of 3H glucosamine into the tissue was unchanged during the experimental period, while the release of 3H-labeled glycoproteins into the medium was markedly increased at 12 h after the onset of stress. The incorporation of 35S-sulfate into the tissue was decreased at 6 h and increased at 12 h. The release of 35S-labeled glycoproteins into the medium was not changed significantly. However, the change in the total radioactivity (tissue plus medium) of 3H was similar to that of 35S. These results suggest that the remarkable increase in the biosynthesis of glycoproteins and sulfated glycoproteins was closely related to reinforcement of defensive response. Furthermore, we investigated the effect of anti-ulcer agents on the biosynthesis of mucus glycoproteins. Cimetidine and atropine decreased the incorporation of radioactive precursors and the release of labeled glycoproteins into the incubation medium in vitro. AAHA (N-(N-acetyl-beta-alanyl)-L-histidine aluminum complex) and sofalcone (SU-88; 2-carboxymethoxy-4,4'-bis (3-methyl-2 butenyloxy) chalcone) increased the incorporation of radioactive precursors and the release of labeled glycoproteins into the medium. These observations indicate that anti-ulcer agents having different modes of action show different effects on the glycoprotein biosynthesis. PMID- 4032217 TI - Anti-tumor activity of 1-acetyl-3-o-toluyl-5-fluorouracil against murine hepatoma MH134 and its effects on tissue weights following subcutaneous and oral administration. AB - Anti-tumor activity of 1-acetyl-3-o-toluyl-5-fluorouracil (A-OT) against MH134 solid tumors in mice was studied following subcutaneous and oral administration and compared with that of 5-fluorouracil (5-FU) administered subcutaneously at doses of 0.2, 0.4 and 0.6 mmol/kg/d. Oral administration of A-OT demonstrated a remarkable effect on MH134 solid tumors, the effect being more marked than that of subcutaneous administration of A-OT. Anti-tumor activity of oral administration of A-OT at a dose of 0.2 mmol/kg/d was comparable to that of subcutaneous administration of 5-FU at the same dose. The level of decrease in thymus weight and the magnitude of increase of spleen weight following oral administration of A-OT at any dose were smaller than those by subcutaneous administration of 5-FU (0.2 mmol/kg/d). PMID- 4032218 TI - Preparation and biopharmaceutical evaluation of microcapsules of ampicillin. AB - Microencapsulation of ampicillin, an orally administered antibiotic, with different viscosity grades of ethyl cellulose was studied. The preparation of microcapsules was done as follows; the mixture of ethyl cellulose-CH2Cl2 ampicillin was dispersed in purified water containing 0.5% (w/w) sodium lauryl benzenesulfonate, and then CH2Cl2 was dried out by elevating the temperature. The dissolution curves for the release of ampicillin from microcapsules prepared using the four different viscosity grades of ethyl cellulose were quite different. The release of ampicillin increased with decreasing ethyl cellulose viscosity. The evaluation of prepared microcapsules was made using gastric emptying-controlled rabbits. The plasma concentration of ampicillin obtained by the administration of microcapsules showed a significant sustained-release pattern. The area under the plasma concentration curve (AUC) of ampicillin obtained after a single oral administration of microcapsules prepared using 10 cps ethyl cellulose was 1.8 times greater than that obtained after double oral administration of powder. This fact will be caused by the delaying of gastric emptying, intestinal-transit and dissolution of ampicillin there. It was confirmed that a large number of microcapsules still remained in the stomach and each microcapsules still contained ampicillin at 24 h after dosing from the experiment using gastric-emptying-controlled rabbits. PMID- 4032219 TI - Intestinal absorption of salicylamide and effect of atropine on it. AB - The effect of atropine (ATR), a parasynpatholytic agent, on the intestinal absorption of salicylamide (SAM) was studied using the absorption kinetic model proposed by Winne et al. The disappearance of SAM from perfusate and the appearance in intestinal blood were determined using perfused intestinal loop of the rat in vivo. The results showed that the absorption of SAM was simulated by the four compartment model consisting of luminal, interstitial, blood and serosal compartments. The model was assumed to have three rate determining factors, namely mucosal membrane permeability, clearance by blood flow and serosal membrane permeability. ATR decreased the absorption of SAM by decreasing the clearance factor relating to intestinal blood flow and increased the fraction of the transported amount of SAM from interstitial space to serosal compartment. PMID- 4032220 TI - Reversible suppression of growth and differentiation of cultured chick myogenic cells with very low concentrations of dibucaine. AB - Dibucaine, a local anaesthetic, reversibly suppressed growth and differentiation of cultured chick myogenic cells. In the presence of 10 microM dibucaine, chick myoblasts multiplied and fused to form myotubes. However, myotubes did not increase their size. Accumulation of creatine kinase (CK) activity per culture dish was also suppressed, showing that myotube growth was suppressed. Concomitantly, myofibril formation and developmental transition of CK isozymes were retarded. The myotubes remained immature. When dibucaine was removed from the culture medium and cells were further incubated, the accumulation of CK activity, especially of muscle type isoform, and formation of myofibrils took place; eventually the myofibrils were organized similarly to those in the control culture. The concentration of dibucaine enough to exert these effects was about one-hundredth of the concentration used in clinical anaesthesia. PMID- 4032221 TI - Promotion of the selective lymphatic delivery of cyclosporin A by lipid surfactant mixed micelles. AB - The absorption of an immunosuppressive drug, cyclosporin A (CsA), with the aid of lipid-surfactant mixed micelles from the rat gastrointestinal (GI) tract and lymphatic delivery were studied. The administration of CsA in oily solution, sesame oil or linolic acid, into the rat duodenum indicated a small amount of CsA both in the plasma and lymph for about 6 h. The administration of CsA in the mixed micellar solution composing of linolic acid and HCO-60, polyoxyethylated (60 mol) hydrogenated castor oil, accelerated the absorption of CsA from the GI tract, and CsA was delivered into the lymphatics with an extremely high selectivity. PMID- 4032222 TI - Transport of theophylline from blood to the intestinal lumen following i.v. administration to rats. AB - The exsorption of theophylline into the small intestinal lumen after intravenous administration of aminophylline was studied by in situ single-pass perfusion technique. As the concentrations of the drug in the serum and the bile juice were decreased, the exsorption rate of the drug into the perfusate decreased obeying the apparent first-order kinetics. The half-lives of the drug concentrations in the serum and the bile juice were 2.13 and 2.58 h for pH 6.0 isotonic phosphate buffer, and were 2.71 and 2.32 h for pH 8.0 isotonic phosphate buffer, respectively. The amounts of theophylline excreted in the perfusate and the bile juice were 12.08% and 0.17% of dose for pH 6.0 isotonic phosphate buffer, and were 13.81% and 0.20% of dose for pH 8.0 isotonic phosphate buffer. These results demonstrated that a considerable amount of theophylline was exsorbed into the intestinal lumen. The mechanism by which oral activated charcoal enhanced clearance of theophylline administered intravenously may be adsorption of the drug transported into the gastrointestinal tract by the charcoal. PMID- 4032223 TI - Event memory: the effects of processing objectives and time delay on memory for action sequences. AB - The memorial representations of events that result from different types of goal directed cognition are conceptualized on the basis of the general model of information processing proposed by Wyer and Srull (1980, 1984). In a test of this conceptualization, subjects read a passage describing the events that took place at a cocktail party. They were told either (a) to form an impression of the party and the events that occurred, (b) to empathize with the person from whose perspective the passage was written, or (c) to remember the information presented in a way that would allow them to reproduce it. The stimulus passage contained two target events, each consisting of actions that were either described chronologically or in reverse order, and were either presented together or were separated by other unrelated material. After either a short or a long delay, subjects recalled the information they read in the order it came to mind. Finally, subjects were given the individual event actions and told to place them in the order they were presented. The actions comprising target events were generally more likely to be recalled together and in chronological order when subjects had learned about them with either an impression formation or an empathy objective than when they had read about them with the goal of remembering them. However, orderings of these actions were affected by task objectives only after a long delay. The effect of task objectives on the order of recalling the events themselves showed a quite different pattern; for example, subjects with an empathy objective were most likely to recall the last target event presented before the first one after a long delay, whereas subjects with an impression objective were least likely to do so. The proposed model provided a reasonable account of these and other effects of task objectives on memory for events and the actions comprising them. PMID- 4032224 TI - Another look at sex stereotypes and social judgments: an analysis of the social perceiver's use of subjective probabilities. AB - Locksley, Borgida, Brekke, and Hepburn (1980) assert that subjects fall prey to the base-rate fallacy when they make stereotype-related trait judgments. They found that subjects ignored their stereotypes when trait judgments were made in the presence of trait-related behavioral information. The present article reexamines those findings with respect to two issues: (a) the use of a normative criterion in comparison with subjects' judgments and (b) the level of analysis (group vs. individual) of subjects' judgments. We conducted a replication of the Locksley et al. (1980) Study 2, and the results were examined with respect to these two issues. We found no support for the base-rate fallacy. When a Bayesian normative criterion was constructed for each subject based on the subject's own stereotype judgments and was compared with assertiveness judgments made in the presence of individuating information, there was no evidence that subjects ignored or underused their stereotypes as the base-rate fallacy predicts. PMID- 4032225 TI - Bystander response to arterial bleeding: helping skills, the decision-making process, and differentiating the helping response. AB - Using a mock injury involving arterial bleeding, we explored the impact of variables on two different decisions in the decision-making process leading to help. Expertise (Red Cross Training), ambiguity, and number of bystanders were manipulated in a 2 X 2 X 2 design. We observed the following responses: (a) nonhelp, (b) ineffective direct help, (c) indirect help, and (d) direct help. The decision to help or not was affected by ambiguity, sex, and the presence or absence of other bystanders. Greater ambiguity led to less help; women helped less than men; and fewer people helped when other bystanders were present. Expertise affected the decision leading to the type of help used but not the decision to help. Although training did not raise the intervention rate, it did dramatically change the effectiveness of the help used and could yield as many as 28 more saved lives out of 80 such incidents. The number of bystanders affected both the decision to help and the type of help used. Ineffective direct help occurred most frequently when the bystander was alone. The presence of other bystanders also affected the type of indirect help that was used. PMID- 4032226 TI - A thematic analysis of the experience of time. AB - A category system describing the human experience of time was developed in efforts to put existing theoretical notions about time ("future time perspective," "time urgency," "object constancy," etc.) into a broader theoretical context. Twenty mature, articulate, well-educated subjects were interviewed about their "experience of time." A thematic analysis of these interviews produced three major categories: (1) Change and Continuity ("becoming in time"), (2) Limits and Choices ("doing in time"), and (3) Tempo ("pacing in time"). The experience of time in various diagnostic groups was discussed in terms of the category system. PMID- 4032227 TI - Race and vulnerability to stress: an examination of differential vulnerability. AB - In this article the possibility of race differences in vulnerability to stress is considered. Structural models linking socioeconomic status, age, and life-change events to psychological distress are fit to blacks' and whites' data, which were obtained in a community survey of 829 Florida residents to evaluate differences in vulnerability. Life-change-distress paths were slightly larger among blacks than among whites, though not significantly so. The possible adaptive or coping resources provided by supportive social ties and by fatalistic responses to chronic stress are suggested as topics for further research with regard to psychological well-being among disadvantaged groups. PMID- 4032228 TI - Preference for control and the coronary-prone behavior pattern: "I'd rather do it myself". AB - We explored differential preference for control among Type A and Type B individuals. Forty-six subjects were threatened with an aversive event (loud noise) and were allowed to choose whether to turn off the noise themselves or to yield control to another (more competent) individual. The results showed that Type B subjects (regardless of sex) tended to relinquish control to their more competent confederates and thus reduce the aversive stimulus, whereas the choice behavior of Type As was less clear. In addition, although female subjects tended to yield control, male subjects were more inclined to retain it. Because the willingness to yield control in general appears to be stronger in women than in men, the behavior observed in Type As may be partly moderated by the subject's sex. Although there were suggestive trends in the data, the central psychological features of the Type A pattern remain ambiguous and await studies in which researchers explore these effects, using a variety of situations and larger sample sizes. PMID- 4032229 TI - Attributional style and the type A coronary-prone behavior pattern. AB - The present two studies examined the attributional styles of Type A and B individuals. Past research suggests that Type A's exhibit greater performance deficits than Type B's following exposure to extended, salient uncontrollable stimuli. The reformulated learned helplessness model suggests that individuals most prone to such performance deficits should exhibit an attributional style characterized by internal, stable, and global attributions for negative outcomes, but external, unstable, and specific attributions for positive outcomes. However, a self-esteem protection explanation of learned helplessness findings predicts an opposite, self-serving attributional style. Results from both studies indicated that Type A's are more self-serving than Type B's in their attributions for positive and negative outcomes. PMID- 4032230 TI - Type A behavior pattern and the judgment of noncontingency: mediating roles of mood and perspective. AB - Past research indicates that Type A's and B's differ in their behavioral responses to lack of control. The present study examined perceptual judgments of noncontingency in an attempt to clarify further the role of a control dynamic in Type A-B differences. Type A's and B's assumed the role of either an actor or an observer on a standard contingency judgment task. Consistent with previous research, both Type A's and B's exhibited an illusion of control when in the role of actor. Only Type B's exhibited an illusion of control when observing another person perform the task. Additional analyses indicated that the absence of an illusion of control by Type A observers reflected accuracy rather than a motivational distortion. Mood was also found to mediate control judgments, but only for actors. The plausibility of a memory-based interpretation for the mood effects is discussed. PMID- 4032231 TI - Personal efficacy, external locus of control, and perceived contingency of parental reinforcement among depressed, paranoid, and normal subjects. AB - Bandura (1982) suggested that judgments of personal efficacy and outcome expectancies (i.e., locus of control) jointly affect behavior. We hypothesized that different combinations of these two sets of beliefs would characterize the thought structures of normal subjects and of psychiatric patients suffering from distinctly different disorders. Normal subjects, depressed subjects, and paranoid subjects completed scales with which we measured beliefs in personal efficacy and beliefs that outcomes are controlled either by chance or by powerful others, as well as a scale with which we assessed perceived contingency of parental reinforcement. The major findings were as follows: Normals judged themselves to be more efficacious than did psychiatric subjects; whereas depressives expected outcomes to be controlled by chance, paranoids expected outcomes to be under the control of powerful others; among the normals, outcome expectancies were strongly associated with personal efficacy, but among the psychiatric patients, these beliefs were unrelated; depressives and paranoids equally reported more noncontingent parental reinforcement than did normals; and perceived contingency of parental reinforcement was predictive of outcome expectancies but not of personal efficacy. The data suggest that low personal efficacy may be a distinguishing characteristic of all psychiatric patients, whereas outcome expectancies may determine the specific nature of the psychiatric disorder. PMID- 4032232 TI - [Pharmaceutical evaluation of a hollow type suppository. II. Indomethacin added form and release characteristics of the hollow type suppository]. PMID- 4032233 TI - [Pharmaceutical evaluation of a hollow type suppository. III. Effect of macrogol 300 on the bioavailability of indomethacin in rabbits]. PMID- 4032234 TI - [Screening test for calcium antagonists in natural products and the active principles of Cnidii monnieri]. PMID- 4032235 TI - [The determination of carteolol in human plasma and urine by high performance liquid chromatography]. PMID- 4032236 TI - [Stability studies on nafamstat mesilate in aqueous solution. II. Studies on the photostability of nafamstat mesilate]. PMID- 4032237 TI - [The variability of plasma protein binding of phenytoin in epileptic patients with hypoalbuminemia]. PMID- 4032238 TI - [Study of crystalline drugs by means of polarizing microscope. VII. Polarizing microscopy of crystalline drugs listed in the Japanese Pharmacopoeia X (3)]. PMID- 4032239 TI - [Stability studies on nafamstat mesilate in aqueous solution. I. Kinetic studies in various pH and temperature conditions]. PMID- 4032240 TI - Integrated pharmacokinetics and pharmacodynamics of atropine in healthy humans. I: Pharmacokinetics. AB - The pharmacokinetics of atropine in three healthy male volunteers after intravenous administration of 1.35 and 2.15 mg of the drug was determined. Pharmacodynamic effects of atropine were measured simultaneously. All the data were fitted to a novel integrated kinetic-dynamic model. Plasma concentrations of atropine and the amounts of atropine and its primary metabolite, tropine, excreted in the urine were measured by a sensitive gas chromatographic-mass spectrometric assay. The kinetics of elimination of atropine was first order. There was evidence that the kinetics of distribution of the drug was dose dependent. Two phases with apparent half-lives of 1 and 140 min were distinguishable in accordance with a linear two-compartment disposition model for atropine. The urinary excretion of unchanged drug was 57% of the dose. The steady state volume of distribution was 210 L, implying extensive tissue binding and/or partitioning. Renal plasma clearance was 660 mL/min, suggesting significant tubular secretion. The renal clearance of atropine depended on urine flow. Urinary excretion of tropine amounted to 29% of the dose. The kinetics of the metabolite was first order. PMID- 4032241 TI - Integrated pharmacokinetics and pharmacodynamics of atropine in healthy humans. II: Pharmacodynamics. AB - This study determined the kinetics of the effects of atropine on heart rate and saliva flow in three healthy male volunteers after intravenous administration of 1.35 and 2.15 mg of the drug. The pharmacokinetics of atropine and its primary metabolite, tropine, were determined simultaneously. Both the pharmacokinetic and effect data were fitted to an integrated kinetic-dynamic model. The maximum heart rate and minimum saliva flow occurred with a significant delay of 7-8 min after drug administration. Both effects were nonlinearly related to the amount of drug in the peripheral compartment. Maximum heart rates of 192 and 217% of the control values were observed at the lower and higher dose levels, respectively. Minimum saliva flows of 8 and 3% of the control values were measured after the lower and higher doses of atropine, respectively. The time durations of the positive chronotropic effect of the drug were 170 and 250 min at the lower and higher dose levels, respectively; the corresponding values for the length of the antisialogogue effect of the drug were 230 and 340 min, respectively. PMID- 4032242 TI - General method for evaluating the fraction of the irreversible organ clearance due to conversion of drug to a primary metabolite. AB - An expression for the fractional metabolic clearance of a drug across an organ has been developed. The expression is a function of areas under the temporal profiles of the drug and metabolite concentrations in the sampling compartment. Formation of the metabolite of interest is permitted throughout the linear systems analyzed. The expression is shown to be applicable to any linear system provided there is only a single direct feed from the organ of interest (compartment where formation of the particular metabolite is being investigated) to the drug-sampling compartment. PMID- 4032243 TI - Binedaline binding to plasma proteins and red blood cells in humans. AB - Serum binding of binedaline, a new antidepressant drug, was studied in vitro by equilibrium dialysis. The percent of binding in serum is high, 99.2%, and remains constant within the range of therapeutic concentrations; no saturation to the binding sites was seen. Investigations performed on isolated proteins with a wide range of concentrations showed one site with a high affinity constant (Ka = 2 X 10(6) M-1) for alpha 1-acid glycoprotein and two sites with a low affinity constant (Ka = 3 X 10(4) M-1) for human serum albumin. Binding to lipoproteins was nonsaturable, with a total affinity constant of 1.25 X 10(5) less than nKa less than 2.79 X 10(6) M-1. Over the range of therapeutic concentrations, the ratio of binedaline concentrations in serum and red blood cells remained constant (1%) and was shown to be dependent on the free fraction of binedaline in serum. PMID- 4032244 TI - Aminopeptidase activity in albino rabbit extraocular tissues relative to the small intestine. AB - Aminopeptidase activity in the corneal epithelium and the conjunctiva of the albino rabbit eye was determined using L-leucine-, L-alanine-, and L-arginine-4 methoxy-beta-naphthylamide as substrates. This was compared with the aminopeptidase activity in the duodenum, jejunum, and ileum. The two ocular tissues were found to be 5-15% as active as the ileum in aminopeptidase activity. There was indirect evidence that the dominant aminopeptidase in the corneal epithelium is different from that in the conjunctiva, suggesting that further studies are warranted to investigate the possibility of delivering certain peptides systemically via the conjunctiva without simultaneously exposing the intraocular tissues to these peptides. PMID- 4032245 TI - Effect of food and tablet age on relative bioavailability and pharmacodynamics of two tolbutamide products. AB - Relative bioavailability and pharmacodynamics of tolbutamide from two different commercially available tablet products have been evaluated in healthy subjects in a single-dose crossover study. "Fresh" tablets and tablets aged by exposure to 98% relative humidity for 3 d at ambient temperature were studied. Aging was found to differentially affect both the rate and extent of absorption for the two products. Differences were reflected by log AUC (generic product AUC 10% lower than the product of the innovator, p = 0.047), peak concentration (generic product 27% lower than the product of the innovator, p = 0.0001), mean absorption time (generic product 119% longer than the product of the innovator, p = 0.0008), and mean residence time (generic product 17% longer than the product of the innovator, p = 0.011). Aged product from the innovator produced statistically significantly higher serum tolbutamide concentrations for the first 8 h postdose and a greater glucose depression than aged generic product. Administration of unaged tablets with food produced differences in the rate of absorption, manifested in time-to-peak (generic product 69% later than the product of the innovator, p = 0.006), peak concentration (generic product 18% lower than the product of the innovator, p = 0.001), and mean absorption time (generic product 104% greater than the product of the innovator, p = 0.007), which resulted in statistically significantly higher tolbutamide concentrations for the product of the innovator than for the generic product for the first 3 h postdose.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4032246 TI - Decomposition of aspirin in the solid state in the presence of limited amounts of moisture. AB - When limited amounts of moisture are added to aspirin in a closed system, the model for decomposition differs from that experienced in an open system, i.e., a system at constant relative humidity. The composition of the liquid decomposition layer on the surface of the aspirin crystals will constantly change, and a model for accounting for both the change in volume and composition of the decomposition layer as a function of time has been developed. Solid-state decomposition data, when plotted as a function of time, exhibit a profile similar to the one predicted, but the position of the decomposition curve observed differs from that of the predicted. The predicted curve indicates better stability than the observed data. PMID- 4032247 TI - Tack behavior of coating solutions III. AB - The effect of finely divided solids on the tackiness of coating solutions was determined using a parallel-plate technique. Results demonstrated that the tackiness of coating solutions containing relatively low concentration of polymers augments with the increase in concentration and diminishes with the increasing particle size of finely divided solids. In contrast, the tackiness of coating solutions containing high concentrations of polymers is suppressed upon increasing the concentration and decreasing the size of finely divided solids. PMID- 4032248 TI - Pharmacologically active conformation of disopyramide: evidence from apparent pKa measurements. AB - We have found evidence that an intramolecular hydrogen bond exists between the amido and pyridine groups of disopyramide in aqueous solutions. This conclusion was reached by a comparison of the pKa values for the basic nitrogen atoms of certain analogues of disopyramide. By comparing the pharmacological actions of disopyramide with those of pheniramine, which lacks an amido group, we have concluded that the constraint on the rotation of the pyridine ring which is imposed by the hydrogen bond is a major determinant of the antiarrhythmic activity. That constraint is, at the same time, a suppressor of the anticholinergic activity. We then concluded that a covalent link would hold the pyridine ring, and the amido group, in the desirable conformation permanently, which would lead to better antiarrhythmic activity and a lower degree of anticholinergic activity. Pharmacological studies on such new molecules are in general agreement with these concepts. PMID- 4032249 TI - Antineoplastic activity of a series of boron analogues of alpha-amino acids. AB - A series of amine cyanoboranes, amine carboxyboranes, and boron analogues of alpha-amino acids have been investigated for antineoplastic activity against the growth of Ehrlich ascites cells. Additional studies demonstrated that the boron analogues inhibited DNA and RNA synthesis at 300 microM. The suppression of DNA synthesis of Ehrlich ascites cells correlated with the reduction of DNA polymerase, 5-phosphoribosyl-1-pyrophosphate amidotransferase, and dihydrofolate reductase activities afforded by the boron compounds. These derivatives did not suppress protein synthesis, thymidylate synthetase, or thymidine monophosphate kinase activities as previously reported for some boron antineoplastic agents. PMID- 4032250 TI - Hypolipidemic activity of 6-amino-2-mercapto-5-methyl-pyrimidine-4-carboxylic acid and related derivatives in rodents. AB - 6-Amino-2-mercapto-5-methylpyrimidine-4-carboxylic acid proved to be a potent hypolipidemic agent in rodents at the low dose of 20 mg/kg/d. The agent effectively reduced the liver enzyme activities required for the synthesis of triglycerides and cholesterol. Lower lipid levels in tissue were observed in mice but not in rats. Preliminary studies indicate that the agent accelerated the excretion of cholesterol and its metabolites from the body. The agents lowered the low-density lipoprotein (LDL) cholesterol content and raised the high-density lipoprotein (HDL) cholesterol content. These changes in lipoprotein cholesterol content suggest that the agent may be helpful in protecting against coronary disease. The agent is more effective than the commercially available agent, i.e., clofibrate at 150 mg/kg/d. PMID- 4032251 TI - Kinetics of hydrochlorothiazide absorption in humans. AB - The kinetics of absorption of hydrochlorothiazide was studied in four adult male volunteers. Plasma levels were monitored for 48 h after a 100-mg dose. Food, electrolyte, and water intake were regulated as far as possible. The plasma level data were fitted to a two-compartment open model with either first-order or zero order absorption, using the pharmacokinetic computer program AUTOAN. A better fit of the data, both graphically and statistically, was obtained with zero-order absorption kinetics. Additional confirmation of absorption kinetics was obtained by treating the plasma level results by the Loo-Riegelman method. Cartesian graphs of the amount absorbed verus time afforded linear plots, which indicate a zero-order process. PMID- 4032252 TI - Dispersion forces and plastic deformation in tablet bond. AB - A model for tablet bond formation is developed. It assumes that attraction forces arise from dispersion forces between surfaces with spherical curvature. The radius of these surfaces depends on the amount of plastic deformation produced during compression. The radius of curvature is calculated by using Hertz's equation for elastic deformation, which is assumed to hold during decompression. The number of contact points per unit cross section is taken as a simple multiple of a number deduced from the particle size, the indentation hardness values, and the solid fraction. A similar approach is used to replace the area per contact point produced when under compression. The resulting equation is used to estimate the bonding index. Values corresponding to the lower range of experimentally determined bonding indices are obtained. Arguments are presented to suggest that large values of the bonding index (tensile strength/indentation hardness) probably result principally from plastic (including viscoelastic) deformation during decompression. Nondispersion forces may contribute but are not believed to be of sufficient magnitude to account for the total bond for materials that exhibit a large value of the bonding index. PMID- 4032253 TI - The influence of solvent on nonaqueous lyotropic liquid crystalline phase formed by triethanolammonium oleate. AB - The geometry of a lyotropic lamellar liquid crystalline phase formed by triethanolamine (TEA) and oleic acid (OLA) with solubilized oligomers of polyethylene glycols and different types of oils was determined from small angle X-ray diffraction patterns. The region of stability of the lamellar liquid crystalline phase on addition of soluble glycols or oils was found to depend on the molar ratio of triethanolamine to oleic acid. A series of ethylene glycol oligomers, which were solubilized in the polar part of the structure, showed maximum solubilization at the OLA-TEA mole ratio of 1.6. The organic oils, on the other hand, which are solubilized into the hydrophobic part of the structure, exhibited maximum solubilization at the OLA-TEA mole ratio of 0.8. PMID- 4032254 TI - Uptake of inhaled n-butyl nitrite and in vivo transformation in rats. AB - The uptake of butyl nitrite by rats (500 g, one rat/chamber) was determined over a 5-min exposure period. About 44% of the starting amount (771-3855 ppm) of n butyl nitrite was consumed in 5 min. Three rats per exposure concentration were individually studied for 0-150 min after exposure. Concentrations of blood methemoglobin and plasma nitrate, nitrite, butyl nitrite, and butyl alcohol were examined. No free nitrite ion or butyl nitrite was detectable in the plasma at any time (6.5-150 min) following the exposure. Concentrations at 6.5 min of butyl alcohol, nitrate ion, and methemoglobin increased with increasing exposure concentrations. Plasma concentrations of butyl alcohol were detectable only briefly at 6.5 and 20 min. Methemoglobin levels decreased linearly at higher concentrations and as an approximate first-order process at lower concentrations (less than 15 g/L of whole blood). By 20 min after the inhalation period, plasma nitrate concentrations had decreased from peak levels to higher than baseline steady-state nitrate concentrations. Nitrosothiols were not detectable in the plasma protein fraction. PMID- 4032255 TI - Amiodarone partitioning with phospholipid bilayers and erythrocyte membranes. AB - The apparent partition coefficient (P) of amiodarone between aqueous buffer and lipid vesicles or erythrocyte ghosts was determined by equilibrium distribution using [125I]amiodarone as a tracer. The lipid vesicles consisted of total lipids extracted from erythrocyte or of egg phosphatidylcholine alone or mixed with a varying amount of stearic acid, phosphatidylethanolamine, sphingomyelin, phosphatidylserine, or cholesterol. All the conditions yielded a similar value of P (P approximately equal to 17,000). The log value of the partition coefficient of the neutral form of the drug is log PN = 5.95. The value of the extrapolated 1 octanol-buffer partition coefficient is log PN,oct = 6.66. Partition coefficient measurements on erythrocyte ghosts suggested that amiodarone partitioned to a similar extent in the protein and lipid content of the membrane. PMID- 4032256 TI - Spirosuccinimides as potential anticonvulsants. AB - A series of spirosuccinimides was synthesized and evaluated for anticonvulsant activity. The study was designed to apply the Topliss approach to structure activity correlations in this novel series of 2-substituted-2-azaspiro[4.4]nonane 1,3-diones and 2,4-disubstituted-2-azaspiro[4.4]nonane-1,3-diones. While no correlation was noted with the 2-substituted derivatives, a good correlation was obtained in the 2,4-disubstituted series, indicating that anticonvulsant activity was related to increasing tau values. The results of these anticonvulsant tests are presented and a rational approach to the structure-activity relationships of spirosuccinimides is provided. PMID- 4032257 TI - Leaching of zinc compound from rubber stoppers into the contents of automatic atropine injectors. AB - This report describes how a material within the cartridge of an automatic injector contaminated its contents. On prolonged storage, a formulation that contained atropine produced lethality in mice. The toxic material originated from zinc compounds that were present in the rubber stopper and plunger of the container and that subsequently leached into the formulation. The contents of cartridges that contained greater than or equal to 0.75 mg/mL of solubilized zinc were lethal to at least 20% of the mice tested; those that contained 0.42 mg/mL showed no lethality. The problem resulted from the physicochemical properties of the rubber, not the concentration of zinc used in the vulcanization process. PMID- 4032258 TI - The mean residence time of drugs in the systemic circulation. PMID- 4032259 TI - Wagner's exact Loo-Riegelman equation: the need for a criterion to choose between the linear and logarithmic trapezoidal rule. PMID- 4032260 TI - Balanced incomplete-block design: its use and misuse. PMID- 4032261 TI - Solubility properties in polymers and biological media 5: an analysis of the physicochemical properties which influence octanol-water partition coefficients of aliphatic and aromatic solutes. AB - Octanol-water partition coefficients of 102 aliphatic, polychloro aliphatic, and aromatic non-hydrogen-bond donor and hydrogen-bond donor solutes are well correlated (r = 0.989, SD = 0.175) by the equation: log Kow = 0.20 + 2.74 V/100 - 0.92 pi - 3.49 beta, where V is the molar volume (taken as the molecular weight divided by the liquid density) and pi and beta are the solvatochromic parameters that measure solute dipolarity/polarizability and hydrogen-bond acceptor basicity. A set of "ground rules" (modifications of the input parameters) are described which allow the inclusion of both aliphatic and aromatic solutes in the same correlation equation. Monomer beta values (betam) are used for alcohol solutes. PMID- 4032262 TI - Predictive relationships in the water solubility of salts of a nonsteroidal anti inflammatory drug. AB - A number of metal and amine salts of the nonsteroidal anti-inflammatory drug 2-(2 fluoro-4-biphenylyl)propionic acid (flurbiprofen) (1) were synthesized, and the water solubilities of these materials were investigated. The solubility of flurbiprofen versus pH is in excellent agreement with the theoretical profile which assumes an intrinsic solubility of 5.0 X 10(-5) M for the free acid and a pKa of 4.22. The solubility determination of 1:1 amine salts of slightly soluble carboxylic acids is complicated by possible precipitation of the free acid when the salt is dissolved in water. The lower than expected apparent salt solubility seen when this phenomenon occurs is referred to as the "stoichiometric solubility." A theoretical treatment delineating three distinct regions in the phase solubility diagram for the tromethamine salt of flurbiprofen illustrates the care which must be taken in characterizing the system for salt solubility determinations. A multiple linear regression analysis was carried out to determine the relationship between the log Ksp of six amine salts and their melting points and cation hydrophilicities. While a strong dependence of Ksp on melting point was found, there was not a significant correlation between Ksp and amine cation hydrophilicity. PMID- 4032263 TI - Analgesic potencies of morphine 3- and 6-sulfates after intracerebroventricular administration in mice: relationship to structural characteristics defined by mass spectrometry and nuclear magnetic resonance. AB - Morphine 3-sulfate, which carries a polar, acidic group at the 3-position much like morphine, does not differ greatly in analgesic potency from morphine following intracerebroventricular administration. This differs from the non ionizable 3-methyl and 3-ethyl ethers, which are less potent analgesics than morphine. Morphine 6-sulfate, which differs from morphine by having an ionizable group at carbon-6 at physiological pH, is a more potent analgesic than morphine following intracerebroventricular administration. Variations in analgesic potency following modifications at the hydroxyl groups appear only to reflect alterations in point charges rather than structural alterations. PMID- 4032264 TI - Hydrolysis and solvent-dependent 2'----5'and 3'----5' acyl migration in prodrugs of 9-beta-D-arabinofuranosyladenine. AB - As a prerequisite to quantitative in vivo studies to further explore the promising topical activity of the 2',3'-di-O-acetyl derivative of 9-beta-D arabinofuranosyladenine (ara-A) against herpes virus infections, the kinetics of solution degradation of the 2',3'-di-O-acetyl derivative and the 2'-,3'-, and 5' monoacetates were investigated. The rates of aqueous solution hydrolysis were found to be consistent with rank order predictions based on a consideration of substituent effects. Preliminary in vivo hydrolysis data, however, do not correlate with such predictions, indicating a need for more systemic studies of the effect of molecular structure on enzyme-catalyzed hydrolysis. An important reaction of the 2'-3'-diester and the 3'-monoester in aqueous solution, in addition to ester hydrolysis, is 3'----5' acyl migration. 2'----5' Acyl migration does not occur in water but is the predominant migration pathway in organic solvents, as verified by studies in acetonitrile. 1H NMR spectroscopy was employed to study the dependence of the conformation of the sugar ring on the solvent environment. Although a change in the equilibrium between the C(2')endo and C(3')endo conformational states does occur, it is not a dramatic change and cannot explain the solvent selectivity observed in the acyl migration kinetics. PMID- 4032265 TI - Computer-assisted structure--anticancer activity correlations of carbamates and thiocarbamates. AB - With the aid of the computer, approximately 8000 compounds that incorporate a carbamate or thiocarbamate moiety, which have been tested as potential anticancer agents at the National Cancer Institute (NCI), were classified and their structure-activity correlations against the in vivo P-388 and L-1210 leukemias were evaluated. Aromatic carbamates and thiocarbamates have shown good activity against P-388 and poor activity against L-1210. The majority of active compounds in this series of aromatic carbamates possess a 2- or 4-heteroatom-substituted phenyl attached to the carbamate oxygen atom or the thiocarbamate sulfur atom with the carbamate nitrogen atom as NHMe. The N-phenyl carbamates were much less active against P-388 than the phenyl carbamates; only bis-N-phenyl carbamates with a methylene bridge between the two phenyl groups showed good activity against both P-388 and L-1210 leukemias. Except for the mycophenolic acid carbamates, the fused phenyl carbamates showed poor activity against both P-388 and L-1210 leukemias. Certain nitrogen-heterocyclic carbamates and carbamates with heteroatom substituents have been selected by the NCI for development toward clinical trials. The nature of the heterocyclic carrier and the position of attachment to the carbamate moiety have a major role on the mode of action of the antitumor activity of these compounds. PMID- 4032266 TI - Altered drug-serum protein binding in the genetically obese Zucker rat. AB - Drug-serum protein binding was evaluated in genetically obese Zucker rats, their lean littermates, and lean Sprague-Dawley rats. The free fraction (fp) of phenytoin was significantly higher in the obese rat (fp = 0.177) compared to its lean littermate (fp = 0.136), apparently due to displacement by free fatty acids. Conversely, diazepam and propranolol fp values were decreased in the obese Zucker rat (fp = 0.107 and fp = 0.122, respectively) compared to the lean Zucker rat (fp = 0.140 and fp = 0.174, respectively). Evidence strongly suggests that the increased binding of propranolol was not due to elevations in the serum concentrations of alpha1-acid glycoprotein (as is the case in the human obese population). Rather, the decreased fp for both diazepam and propranolol was a result of increased lipoprotein partitioning. Strain differences between the lean Zucker rat and lean Sprague-Dawley rat were also evident, with serum binding of the Sprague-Dawley rat more closely resembling the obese Zucker rat. PMID- 4032267 TI - Improvement of dissolution and suppository release characteristics of flurbiprofen by inclusion complexation with heptakis(2,6-di-O-methyl)-beta cyclodextrin. AB - The inclusion behavior of methylated beta-cyclodextrins, heptakis(2,6-di-O methyl)-beta-cyclodextrin and heptakis-(2,3,6-tri-O-methyl)-beta-cyclodextrin in solution and the solid state was compared with that of natural beta-cyclodextrin using an anti-inflammatory drug, flurbiprofen, as a guest molecule. Stability constants were determined by the solubility method at various temperatures, and the thermodynamic parameters were calculated for inclusion complex formation in aqueous solution. The solid complexes were obtained in a molar ratio of 1:1, and their dissolution behavior and release from suppository bases were examined. The data suggest that the inclusion mode of the complex with 3 is somewhat different from that of the complexes with 1 and 2. From a practical point of view, 2 seems to be particularly useful for improving the pharmaceutical properties of flurbiprofen in various dosage forms. PMID- 4032268 TI - Liquid chromatographic analysis of enviradene, a new antiviral agent, in plasma and its application in bioavailability studies in the dog. AB - A rapid and specific high-performance liquid chromatographic (HPLC) assay has been developed for the determination of enviradene, 1, at concentrations of 2-5 ng/mL in plasma. The drug was extracted from the samples using benzene. The benzene extract was evaporated and the residue dissolved in the mobile phase. The HPLC system consisted of a reversed-phase column and a 75% methanol:25% 0.2 M sodium acetate mobile phase. Either a UV detector set at 268 nm or an electrochemical (EC) detector set at a potential of +0.9 V (versus Ag/AgCl/3 M NaCl) was used to monitor the drug. A column-switching system was used to remove late-eluting plasma constituents that interfered in subsequent chromatograms. The limit of sensitivity was 2 ng/mL for the HPLC-EC procedure and 5 ng/mL for the HPLC-UV procedure. Recovery from plasma was approximately 97%; the procedure had a relative error of approximately 3% and a relative standard deviation of 4.5% over the range of 20-200 ng of 1/mL of plasma. Following intravenous administration of 1 or 2 mg/kg of 1 to dogs, the parent drug was quantitated in plasma for 24 h using this procedure. The terminal phase half-life in plasma was calculated to be 10 h. Oral administration to dogs of single 8 mg/kg doses of 1, formulated with povidone-30 or polysorbate 80 and microcrystalline cellulose, produced high and persistent plasma concentrations of drug. At doses below 2 mg/kg, plasma concentrations were found to be nonlinearly related to the amount of the dose administered. The bioavailability of the drug in dogs was found to be increased by the concomitant administration of food. PMID- 4032269 TI - Chlorthalidone pharmacodynamics in beagle dogs. AB - A pharmacodynamic approach was employed to examine the diuretic effect of chlorthalidone in beagle dogs and to identify parameters necessary for optimization of an oral dosage formulation of this drug. The extensive partitioning of chlorthalidone into erythrocytes was shown to be noninstantaneous, with an in vitro partitioning half-life of 18 min. In vivo studies using oral and intravenous solutions confirmed this finding. Additionally, the diuretic effect was demonstrated to be related to the drug concentration in the plasma fraction. These studies led to the development of a relevant pharmacokinetic model which highlighted the importance of the oral absorption rate on the diuretic efficacy of chlorthalidone. A novel, rapidly dissolving, stabilized, amorphous chlorthalidone tablet formulation was compared to various oral solution and tablet formulations. Pharmacokinetic analysis by classical compartmental models and by moment techniques demonstrated that the rapidly dissolving tablet formulation was bioequivalent to an oral solution of chlorthalidone. Preparations containing crystalline chlorthalidone are shown to be incompletely absorbed, and the rates of absorption favor partitioning into the erythrocyte fraction. It is projected from the pharmacodynamic model that the novel chlorthalidone preparation optimizes plasma levels necessary to invoke a diuretic response. PMID- 4032270 TI - Degradation of chlorthalidone in methanol: kinetics and stabilization. AB - The reaction of chlorthalidone with methanol to give the corresponding methyl ether was investigated. The kinetics are pseudo-first-order in chlorthalidone, but the observed pseudo-first-order rate constants show an unexpected dependence on the initial chlorthalidone concentration, attributable to the presence of trace catalytic impurities in commercial chlorthalidone. Evidence is presented to show that trace heavy metals are probably responsible for the primary catalytic effect. Trace quantities of acetic acid are also present and show a smaller secondary catalytic effect. Kinetics in the presence of added heavy metals and acetic acid were examined. EDTA and povidone reduce the degradation rate. Stabilization by EDTA is due to its ability to chelate heavy metals. Stabilization by povidone is also primarily due to its ability to complex heavy metals; complexation data of ferric and nickel ions with povidone and with 1 methyl-2-pyrrolidinone as a monomer model are presented. In addition, complexation constants were calculated for the interaction of povidone with chlorthalidone, which may also play a role in stabilization. PMID- 4032271 TI - Effects of magnesium oxide on trichlormethiazide bioavailability. AB - The effect of an antacid, magnesium oxide (MgO), on the bioavailability of a thiazide diuretic, trichlormethiazide, was studied in 10 healthy subjects who fasted overnight. A single oral dose of 4 mg of 1 alone or in combination with 0.5 g of MgO was given in a two-way Latin-square crossover design. Urine concentrations of 1 during the 24 h after each dose were determined by an HPLC method. There were no significant differences for drug alone versus drug with MgO in the mean percentage recovery (60 versus 62%) and the cumulative amount excreted unchanged in urine over 24 h (2408 versus 2463 micrograms). However, coadministration of MgO increased the mean excretion rate of 1 at 0.75 h and 1.5 h (p less than 0.05), the cumulative amount excreted unchanged in urine over 2 h (p less than 0.05), and the absorption rate constant (p less than 0.05). Therefore, the extent of bioavailability was not influenced by MgO, but the rate of absorption was enhanced. The solubility of 1 increased remarkably by changing from pH 1.2 to 8.0 (141 to 1365 micrograms/mL). The dissolution rate of 4 mg of 1 in 500 mL of medium was not affected by an increase in pH. However, a 1.5-fold increase of the dissolution rate in 20 mL of medium was observed by changing from pH 1.2 to 7.3.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4032272 TI - Bioequivalence of carbamazepine chewable and conventional tablets: single-dose and steady-state studies. AB - Single-dose and steady-state studies were carried out on separate occasions to examine the bioequivalence of the newly formulated carbamazepine chewable tablet. In the single-dose study, the plasma levels resulting from 2 X 200-mg conventional tablets (CT), 4 X 100-mg chewable tablets swallowed whole (SW), and 4 X 100-mg chewable tablets chewed before swallowing (CHEW) were compared. A randomized 3 X 3 Latin-square design balanced for residual effects, with a 3-week washout period, was used (n = 6). Plasma samples were analyzed by a specific GC method for carbamazepine. The following parameters were used for evaluation: AUC, Cmax, tmax, and t1/2. None of the parameters were significantly different except Cmax and t1/2 values for CHEW and CT. The Cmax was 25% higher and t1/2 was 11% shorter for CHEW than CT. The impact of differences in the peak plasma levels at steady state were examined by pharmacokinetic projection (400 mg b.i.d.) based on the single-dose data and with simulated induction equal to a 50% reduction in t1/2. The projected steady-state CT and CHEW plasma concentrations were similar, with a difference of only 4%. The results demonstrate the bioequivalence of the dosage forms with respect to the extent of absorption, and similar steady-state concentrations of carbamazepine in plasma can be expected. To test the conclusion from the projected study, a separate bioequivalence study to compare CHEW relative to CT was performed at steady state in normal volunteers (200 mg b.i.d.).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4032273 TI - Bioanalysis and disposition of alpha-fluoromethylhistidine, a new histidine decarboxylase inhibitor. AB - A sensitive, selective, and rapid high-performance liquid chromatographic procedure was developed for the determination of alpha-fluoromethylhistidine (alpha-FMH) in human biological samples. The plasma assay required isolation of the drug using a weak cation-exchange resin prior to HPLC analysis with UV detection. The urine assay employed postcolumn derivatization with o phthalaldehyde (without a thiol) and fluorescence detection. The extent of metabolism of alpha-FMH in humans was studied in four healthy volunteers using tritium-labeled material. No significant differences in the plasma and urine concentrations of radioactivity and unchanged drug were detected. In addition, the radiochromatograms of selected urine samples revealed a single peak with a retention time corresponding to the unchanged drug. The evidence presented suggests negligible biotransformation of alpha-FMH in humans. PMID- 4032274 TI - Pharmacokinetics of propylene glycol in humans during multiple dosing regimens. AB - The pharmacokinetics of propylene glycol has been examined during multiple oral dosing regimens. The glycol is rapidly absorbed, with Cpmax observed within 1 h following administration. The terminal elimination half-life is approximately 4 h. After a minimum of 10 half-lives of maintenance dosing on a fixed regimen, the accumulation of propylene glycol differed significantly among individuals because of variability in apparent clearance. The average apparent total body clearance is approximately 0.1 L/kg X h and may be concentration dependent. The apparent volume of distribution is approximately 0.5 L/kg, approximating total body water. PMID- 4032275 TI - Serum-catalyzed hydrolysis of metronidazole amino acid esters. AB - Glycine (Gly), alanine (Ala), valine (Val), leucine (Leu), isoleucine (Ile), phenylalanine (Phe), and lysine (Lys) esters of metronidazole were synthesized using dicyclohexylcarbodiimide (DCC) coupling or a mixed-anhydride route, using tert-butyloxycarbonyl (tert-Boc) amino acids. Human serum-catalyzed hydrolysis of these esters at 37 degrees C give half-lives varying from 4.5 min for the Phe ester to 96 h for the Ile ester. Also determined was the pH-rate profile for hydrolysis in aqueous buffers at 25 degrees C. A linear relationship was observed between the logarithmic value of the hydrolysis rate constant in serum and that of the OH- -catalyzed hydrolysis of cationic esters. This finding may indicate that the esters studied are "equally" poor substrates for binding to the enzymes in serum and, thus, the difference observed in the serum-catalyzed hydrolysis rate is solely derived from the chemical lability of an ester bond. Interestingly, the extent of chemical activation observed in the buffer system appears to be amplified in the serum-catalyzed hydrolysis. PMID- 4032276 TI - Automated flow-injection pseudotitration of boric acid. AB - An automated flow-injection pseudotitrimetric determination of boric acid, using a flow-injection photometric analyzer controlled by a microcomputer, is described. The method is based on the injection of 200 microL of sample in a flowing stream of mannitol-bromothymol blue "titrant" and measuring the peak width in time units. Equivalent times of 10-70 s are measured with CV values of 0.1-0.4% (n = 5) and the analytical range is 1.5-309 mg/100 mL (2.5 X 10(-4)-5 X 10(-2 M) of boric acid. The method was evaluated by performing recovery studies in mixtures (mean 99.8%) and assays of commercial preparations which were compared with the official classical titrimetric method. PMID- 4032277 TI - 4-Methylpyrazole disposition in the dog: evidence for saturable elimination. PMID- 4032278 TI - Impact of liposomal drug carriers on drug pharmacokinetics. PMID- 4032279 TI - Alternate interpretation of the role of water in the erythromycin structure. PMID- 4032280 TI - Commercial aluminum hydroxide. PMID- 4032281 TI - Additive protection of cimetidine and N-acetylcysteine treatment against acetaminophen-induced hepatic necrosis in the rat. AB - Cimetidine protects against acetaminophen hepatotoxicity in the rat as evidenced by improved survival, lower serum aminotransferases, improved liver histology, decreased in vivo and in vitro covalent binding of acetaminophen to liver protein and decreased rate of glutathione depletion. This protection is best explained by inhibition of acetaminophen oxidation by cimetidine. N-acetylcysteine, the accepted antidote, protects against acetaminophen hepatotoxicity primarily by enhancing glutathione synthesis. Inhibition of acetaminophen oxidation by cimetidine has been demonstrated directly in vitro with both rat and human liver microsomes. The aim of the present study was to determine whether cimetidine and N-acetylcysteine might be additive in their protection against acetaminophen hepatotoxicity as cimetidine and N-acetylcysteine have different mechanisms of protective action. Treatment with either cimetidine or N-acetylcysteine improved survival and serum transaminases in a dose-related manner but protection by the combination was additive when compared to each agent alone. Cimetidine decreased the rate of hepatic glutathione depletion and acetaminophen covalent binding in vivo in a dose-dependent manner whereas only a high dose of N-acetylcysteine decreased covalent binding. However, the combination of cimetidine and N acetylcysteine more effectively prevented glutathione depletion and covalent binding in vivo than either agent used alone. We conclude that protection against acetaminophen hepatotoxicity using a combination of cimetidine and N acetylcysteine is better than that found with either agent alone. Inasmuch as cimetidine does not increase hepatic glutathione per se, or does N-acetylcysteine inhibit acetaminophen oxidation, the additive protection against acetaminophen hepatotoxicity is best explained by the above mentioned mechanisms of action for each agent. PMID- 4032282 TI - Effect of gossypol on erythrocyte membrane function: specific inhibition of inorganic anion exchange and interaction with band 3. AB - The effects of gossypol on membrane functions of the human erythrocyte were studied. Gossypol (10 microM) had no effect on spontaneous hemolysis, osmotic fragility, cell volume, cholinesterase activity, hexose transport, ouabain sensitive inorganic cation transport, ouabain-insensitive inorganic cation transport and nucleoside transport. Conversely, 10 microM gossypol inhibited inorganic anion transport by approximately 90% for three different substrates, i.e., phosphate, sulfate and chloride. Inhibition of inorganic anion transport was specific as 10 microM gossypol had no effect on the eight aforementioned membrane-related functions of the human erythrocyte. Inhibition inorganic anion transport was characterized using sulfate as the substrate and had the following features: it was potent, with a Ki of approximately 3 microM; it was rapid, with onset occurring in less than 1 min; it was potently blocked by physiological concentrations of albumin and plasma with 50% blocking achieved at 0.03% (w/v) albumin; it occurred by a noncompetitive kinetic mechanism; it was independent of medium Ca++, Mg++ or pH. Gossypol was bound to human erythrocytes and cell membranes isolated from erythrocytes. 4,4'-Diisothiocyanostilbene-2,2'-disulfonic acid is a potent inhibitor of anion transport and can be covalently bound to band 3. Covalently bound 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid blocked a fraction of gossypol binding to erythrocyte membranes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4032283 TI - Effect of hypoxia and pregnancy on antipyrine metabolism in isolated perfused rat livers. AB - The effect of hypoxia on antipyrine metabolism was studied in isolated perfused livers from pregnant (19-21 days gestation) and nonpregnant female Wistar rats. Hypoxia was induced by altering the blood content and/or flow rate of the recirculating perfusion medium. Inflow and outflow pO2 values, in themselves, were not valid indicators of oxygen delivery and consumption when the liver was perfused with a blood containing medium. At a given oxygen delivery rate, oxygen consumption per gram of liver was the same in nonpregnant and pregnant rat livers. The absolute clearance of antipyrine (milliliters per hour) was significantly greater in livers from pregnant compared to nonpregnant rats, whereas antipyrine clearance, corrected for liver weight (milliliters per hour gram of liver), was significantly lower in pregnant rat livers. Antipyrine clearance (milliliters per hour) was linearly related to oxygen consumption (milliliters per minute or micromoles per minute per gram of liver) in both the nonpregnant and pregnant rat livers. As oxygen consumption decreased, livers from pregnant rats maintained a greater ability to clear antipyrine than livers from nonpregnant rats. This study emphasizes the importance of maintaining adequate oxygen delivery to isolated perfused livers during drug metabolism studies to ensure constant oxygen consumption. Otherwise, alterations in the flow rate or hematocrit of the perfusion medium may directly alter the elimination rate of the substrate. PMID- 4032284 TI - Effects of albumin and alpha-1 acid glycoprotein on elimination of prazosin and antipyrine in the isolated perfused rat liver. AB - This study was undertaken to investigate the effect of albumin and alpha-1 acid glycoprotein on the elimination of drugs with a low extraction ratio in the isolated perfused rat liver. The unbound clearance of prazosin increased 69% after the addition of 14 mg/ml of albumin to the perfusate whereas the unbound clearance decreased by 51% after the addition of 0.85 mg/ml of alpha-1 acid glycoprotein. The clearance of antipyrine, a compound not bound to albumin or alpha-1 acid glycoprotein, increased 28% in the presence of albumin but was not altered in the presence of alpha-1 acid glycoprotein. These results suggest that albumin has the ability to enhance the elimination of drugs both bound and not bound to albumin. This effect was found not to be related to pH changes across the liver or to the oncotic pressure effect of albumin. Alpha-1 acid glycoprotein, on the other hand, seems to be able to decrease the elimination of drugs which bind to it, but has no effect on drugs that are not bound. PMID- 4032285 TI - Phencyclidine (PCP) disposition kinetics in dogs as a function of dose and route of administration. AB - Phencyclidine (PCP) disposition kinetics has been examined in dogs as a function of dose and after i.v. and p.o. administration. Intravenous doses ranged from a tracer quantity of [3H]PCP to 5 mg/kg of unlabeled PCP. The elimination half-life of intact PCP was relatively short with harmonic mean values of 2.7, 5.4 and 3.9 hr for the tracer, 1- and 5-mg/kg doses, respectively. In contrast, measurement of total radioactivity gave a much longer half-life (35-52 hr) suggesting slower metabolite elimination. The drug has a large apparent volume of distribution (weighted mean of 20 liters/kg) and a systemic clearance (which is primarily metabolic) that approaches estimates of liver blood flow in the dog. Renal clearance of intact PCP represents a small fraction of total clearance. Percentage of the [3H]PCP dose recovered as total radioactivity was 49% in urine and 12% in feces. Several metabolites of PCP were determined in urine and they account for about 30% of the dose with the aminopentanoic acid derivative being present in the greatest amount. One of the hydroxylated metabolites is present in cis- and trans-forms, with the latter predominating. Three animals received an i.v. dose of [3H] PCP and a p.o. dose of unlabeled PCP at the same time to determine absolute bioavailability. Approximately 25% of the dose is absorbed intact. The p.o. (intrinsic) clearance of PCP is about four times greater than systemic clearance suggesting a blood flow-dependence in clearance and substantial first-pass hepatic metabolism. PMID- 4032286 TI - Phenotypic differences in mephenytoin pharmacokinetics in normal subjects. AB - The urinary metabolic profile of mephenytoin and its oxidative metabolites indicates significant stereoselective metabolism of its two enantiomers. Also, polymorphic oxidation, which is present in about 2 to 5% of the Caucasian population, has been demonstrated by an impaired ability to 4-hydroxylate this anticonvulsant. In order to determine the consequences of such metabolism, the plasma concentration/time profiles of the enantiomers of mephenytoin and its N demethylated metabolite, phenylethylhydantoin (PEH), were investigated after a single p.o. dose of racemic mephenytoin in normal subjects with different metabolizing ability for mephenytoin [extensive metabolizer (EM) vs. poor metabolizer (PM) phenotypes]. In the EM subjects, the disposition of S- and R mephenytoin was markedly different with a 100- to 200-fold difference in mean oral clearance (4.7 vs. 0.027 liters/min) and a 30- to 40-fold difference in elimination half-life (2.1 vs. 76 hr). In these same subjects, R-PEH concentrations significantly accumulated over several days and then very slowly declined with an apparent half-life of about 200 hr. Plasma levels of S-PEH were essentially negligible. In contrast, the stereoselective elimination of mephenytoin was reduced markedly in subjects of the PM phenotype, with the disposition of the S-enantiomer being the same as that for R-mephenytoin, which in turn was similar to that observed for this enantiomer in EMs. Almost comparable plasma levels of S- and R-PEH were also present in PMs. Only a small amount (less than 5%) of unchanged mephenytoin was excreted in the urine regardless of phenotype.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4032287 TI - Alteration of transit time and direction of flow to probe the heterogeneous distribution of conjugating activities for harmol in the perfused rat liver preparation. AB - Previous studies in the once-through perfused rat liver preparation have shown that the techniques of normal and retrograde delivery of substrate and computer simulation of enzyme distributions along the sinusoidal flow path in liver were useful in delineating the relative distributions of sulfation and glucuronidation activities for harmol metabolism (Pang et al., J. Pharmacol. Exp. Ther. 224: 647 653, 1983). The observed steady-state hepatic extraction ratios of harmol and the steady-state formation rates of harmol sulfate and harmol glucuronide were consistent with three enzyme-distribution models which described a proximal localization of sulfation activity and a more distal distribution of glucuronidation activities. The present study was a further refinement on the definition of the distribution of these activities. The experimental approach used included the perturbation of delivery of harmol (10 microM) at 8, 12 and 16 ml/min by normal flow, and the alternation of normal and retrograde directional flows for delivery of harmol (10 microM) at constant hepatic blood flows (8, 12 or 16 ml/min) in the single-pass perfused rat liver preparation. The observed steady-state sulfation and glucuronidation rates were compared against predicted values afforded by models previously shown to be adequate and additional enzyme distributed models. The observed and predicted data point to a periportal distribution of sulfation activity and an even distribution of glucuronidation activity for the metabolism of harmol. PMID- 4032288 TI - Binding of drugs with a quaternary ammonium group to alpha-1 acid glycoprotein and asialo alpha-1 acid glycoprotein. AB - The interaction of eight mono- and four bisquaternary ammonium compounds with alpha-1 acid glycoprotein and its desialylated derivative was investigated. Protein binding was performed in vitro by equilibrium dialysis at 37 degrees C. The simple monoquaternary ammonium compounds tributylmethylammonium, tripropylmethylammonium, triethylmethylammonium and procainethobromide were not appreciably bound (unbound fraction greater than 0.99). Excellent negative correlations of unbound fraction and the log of the octanol/Krebs' partition coefficient were obtained for thiazinamium, N-methylimipramine, N methyldeptropine and d-tubocurarine, both for alpha-1 acid glycoprotein (r = 0.99) and asialo alpha-1 acid glycoprotein (r = -0.94). Bisquaternary ammonium compounds, with the exception of hexafluorenium, were only poorly bound. Our binding data on N-methyl-deptropine, N-methylimipramine and thiazinamium reveal that these compounds are more avidly bound to alpha-1 acid glycoprotein than to albumin, in spite of their polar character. The interaction of N-methyldeptropine with alpha-1 acid glycoprotein was studied in more detail. Scatchard plots revealed the presence of two classes of binding sites. N-Methyldeptropine could effectively be displaced by imipramine from its high-affinity binding site. This points to the presence of a common high-affinity binding site for tertiary and quaternary ammonium compounds on alpha-1 acid glycoprotein. PMID- 4032289 TI - Peroral treatment of diabetes insipidus with a polypeptide hormone analog, desmopressin. AB - In the present study nine diabetes insipidus patients were treated with desmopressin (DDAVP) tablets. All patients had a significant reduction of their polyuria after a peroral dose of 50 micrograms DDAVP. During a 6-day trial, a peroral treatment with two or three daily peroral doses of DDAVP controlled their polyuria. A dose-response study in five of the patients indicated that peroral DDAVP doses as small as 10 micrograms have effects on renal concentrating ability. A log-linear relationship was found between DDAVP doses and maximal urine osmolalities and duration of antidiuresis. Measurements of plasma DDAVP concentrations after peroral DDAVP revealed a linear relationship between amounts of DDAVP absorbed and dose, but with great interindividual differences. The results indicate that graded renal response occur at plasma concentrations of DDAVP between 1 and 5 pg/ml. The results of this study and the assessment by the patients of the treatment indicate that peroral therapy with DDAVP may be an attractive alternative to traditional intranasal administration of the drug. PMID- 4032290 TI - Hypernoradrenergic innervation of the caudal artery of the spontaneously hypertensive rat: an influence upon neuroeffector mechanisms. AB - In the present studies we have established that the perfused caudal artery from spontaneously hypertensive (SH) rats responds to pharmacological and physiological stimuli in a manner similar to that described for other blood vessels from the SH rat. In addition, the responses of caudal arteries from SH rats to exogenous norepinephrine were similar to those of arteries removed from normotensive Kyoto Wistar rats. However, responses to sympathetic nerve stimulation at high, but not low, frequencies of stimulation were increased in arteries from the SH rat. In addition, impairment of neuronal uptake with cocaine unmasked a greater responsiveness of arteries from SH rats to sympathetic nerve stimulation. Consistent with the latter finding the neuronal uptake and neuronal deamination of norepinephrine was larger in caudal arteries from SH rats. A histofluorescent and electron microscopic analysis of the sympathetic innervation of caudal arteries from SH and Kyoto Wistar rats demonstrated that the vessels from SH animals had a greater number of nerve axon bundles and a greater area of adventitia occupied by nerve bundles. It is concluded that the ability of high rates of nerve stimulation and cocaine to unmask an enhanced responsiveness of caudal arteries from SH rats is related to an enhanced innervation of the artery. It is suggested that in the SH rat model of hypertension future research into the causes of the augmented blood pressure should be directed toward factors regulating the density of the sympathetic innervation of the vasculature. PMID- 4032291 TI - Barbiturate-induced alterations in the kinetic parameters of slow outward current in Aplysia giant neurons. AB - Regulation of spike frequency adaptation has been postulated to be a neuronal mechanism of action of the barbiturates (Zbicz and Wilson, 1981). A barbiturate sensitive slow outward current is present in Aplysia giant neurons, and this current is very effective at regulating adaptation. In the current study a quantitative method of determining the effect of barbiturates was developed using a single-electrode voltage clamp. This method, tail current analysis, involved measuring the exponential decay of the slow outward current at the end of a depolarizing voltage-clamp command. The tail currents were made up of two decay phases with average half-times of 7 and 70 sec, and the tail current amplitude accurately reflected the magnitude of slow outward current. Barbiturates were found to cause a concentration-related, saturable and stereospecific increase in one component of the tail currents, the amplitude of the slow phase. With moderate concentrations of barbiturates there were no changes in the other parameters describing the exponential decay current. The rank order of potency of barbiturates for the enhancement of slow outward current was not well correlated with the lipid solubility of these drugs, indicating that slow outward current enhancement is not due to a nonspecific mechanism, but rather may be receptor mediated. PMID- 4032292 TI - Influence of the blood-brain pH gradient on brain phenobarbital uptake during status epilepticus. AB - Brain uptake and blood concentrations of phenobarbital were determined in rats during pentylenetetrazol-induced status epilepticus and compared to nonconvulsing controls. Brain phenobarbital concentrations and the brain-to-blood phenobarbital ratio were increased 2-fold in freely convulsing animals as compared to controls. The degree of systemic acidosis during motor convulsions was greater than the degree of brain acidosis. Because phenobarbital is a weak acid, this pH gradient favors movement of phenobarbital into the brain during status epilepticus. Motor paralysis prevented the development of systemic acidosis and the brain-blood partition of phenobarbital was similar to that of nonconvulsing controls. Blood phenobarbital concentrations were slightly higher in animals paralyzed during status as compared to controls, presumably due to hemodynamic effects of convulsions. These studies, as well as our previous studies with lidocaine, support the idea that the brain-blood pH gradient is an important determinant of drug uptake by the brain during seizures. PMID- 4032293 TI - The post-natal development of cutaneous afferent fibre input and receptive field organization in the rat dorsal horn. AB - The responses evoked in lumbar dorsal horn cells by both natural and electrical hind-limb skin stimulation were recorded in the spinal cord of rat pups aged 0-15 days under urethane anaesthesia. The input volley was recorded on the L4 dorsal root and consisted of two separate waves from birth. Latency and threshold measurements were consistent with these two waves being immature A (myelinated fibre) waves and C (non-myelinated fibre) waves. On the first 3 days of life background activity of cells in the dorsal horn was low and evoked discharges were sluggish. On electrical stimulation of the skin, neonatal dorsal horn cells frequently responded with only 1 or 2 impulses per input volley with long central delays of up to 20 ms. Synaptic linkage appeared weak and many cells failed to follow stimulation rates of 5 Hz. Natural skin stimulation showed that the majority of cells at days 0-3 responded to pinching the skin only. The development of responses evoked by C fibres in the dorsal horn was delayed compared to that of responses evoked by A fibres. Short and long latency responses corresponding to the early A and late C afferent input volleys could be recorded in the superficial laminae (I, II and III) of the dorsal horn from day 0, but in the deeper laminae only early short latency A responses were evoked until the age of day 7-8. After this time, a long latency C response also appeared and increased in strength with age. Convergence of low and high threshold inputs onto dorsal horn cells was rare at birth but increased gradually over the following two weeks. Receptive field areas, mapped by natural mechanical stimulation of skin, were large at birth and decreased in size with age. At birth the mean receptive field area was 14.2% of the total hind-limb area whereas at day 15 it was 3.6%. This fall in size was particularly marked in cells of the deep dorsal horn. Pinching or brushing the receptive field of many neonatal dorsal horn cells resulted in long-lasting after-discharges (30-90 s) which on days 0-3 could be more pronounced than the initial evoked response. The duration and amplitude of these responses decreased with age. Repetitive electrical skin stimulation of the receptive fields of these cells produced 'wind-up' and prolonged after-discharge. Ipsilateral, contralateral and distant inhibitory components to receptive fields were observed from day 0.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 4032294 TI - The relationship between intracellular calcium and contraction in calcium overloaded ferret papillary muscles. AB - The photoprotein aequorin was microinjected into cells on the surface of ferret papillary muscles. Tension and aequorin light, a function of intracellular Ca concentration ([Ca2+]i), were monitored. The preparations were exposed to increased concentrations of extracellular Ca ([Ca2+]o). Small increases in [Ca2+]o led to the usual increase in both the systolic light signal and the developed tension. However, high [Ca2+]o led to a fall in developed tension known as Ca overload. This fall of tension was seen at lower [Ca2+]o if the experiment was performed in the presence of strophanthidin. In conditions of Ca overload, the systolic light signal was either similar in amplitude or larger than the systolic light observed under conditions which did not lead to Ca overload. Oscillations of diastolic light were invariably present under conditions of Ca overload. These oscillations were accompanied by after-contractions which were small in relation to the magnitude of the aequorin light oscillations. During Ca overload, the variance of the amplitude of the systolic light signal was greater than could be accounted for by the random nature of the arrival of photons. Small systolic light signals occurred when there had been an oscillation of light in the diastolic period immediately preceding the systolic light signal. Large systolic light signals occurred when the preceding period (approximately 1 s) was free of oscillations of light. These observations suggest that if the sarcoplasmic reticulum (s.r.) has spontaneously released its contents of Ca as shown by a diastolic [Ca2+]i oscillation, then a stimulated systolic Ca signal occurring within about the next second is smaller, possibly because it takes longer than this period for the s.r. to reload with Ca. If this process occurs randomly in the various cells of the preparation, developed tension will be reduced because those cells which have a small Ca release will act as a compliance in series with cells which have a large Ca release. PMID- 4032295 TI - Properties of a sympatho-inhibitory and vasodilator reflex evoked by superior laryngeal nerve afferents in the cat. AB - The background discharge of sympathetic preganglionic neurones shows a marked inspiration-synchronous component which is known to originate from within the central nervous system. The contribution of this component to total neurogenic vasoconstrictor tone is unknown. In order to estimate its extent we have exploited the inspiration-suppressing effect of a group of low threshold afferent fibres in the superior laryngeal nerve. The electrical activities of the cervical sympathetic trunk and of the phrenic nerve were recorded in pentobarbitone anaesthetized, paralysed, artificially ventilated, sino-aortic denervated and vagotomized cats, together with the perfusion pressure of an innervated hind limb perfused at a constant flow rate. Repetitive stimulation of the superior laryngeal nerve at an intensity just sufficient to suppress phrenic nerve activity inhibited the inspiration-synchronous sympathetic discharge and caused hind limb vasodilatation. This vasodilatation was abolished by hexamethonium or phentolamine, but was not affected by atropine or propranolol. Following the elimination of phrenic nerve activity and inspiration-synchronous sympathetic discharge by systemic hypocapnia, repetitive stimulation of the superior laryngeal nerve either failed to affect the residual sympathetic activity and hind limb perfusion pressure, or caused an increase of both. Stimulation of the superior laryngeal nerve with short (0.2 s) trains of stimuli, delivered at selected times of the respiratory cycle for several consecutive cycles, had similar effects on phrenic nerve bursts, inspiration-synchronous sympathetic discharge and hind limb perfusion pressure. Stimulation at progressively earlier times during inspiration produced a graded reduction in all three variables, while stimulation during late inspiration or early expiration had no effect on any of them. The results suggest that the vasodilator reflex, elicited by inspiration-suppressing afferents in the superior laryngeal nerve, results from selective abolition of the excitatory input which causes the inspiration synchronous discharge of sympathetic neurones. The magnitude of the hind limb vasodilatation can therefore be taken as an indication of the extent of control of hind limb vasoconstrictor tone exerted by this particular input. By comparing the magnitude of the reflexly evoked vasodilatation with that of the vasodilatation resulting from ganglionic blockade, it was estimated that 24.2% of the neurogenic vasoconstrictor tone of the hind limb was attributable to the inspiration-synchronous component of sympathetic discharge. PMID- 4032296 TI - The possible relation between mastication and parotid secretion in the rabbit. AB - Salivary flow has been recorded from conscious rabbits during 1 min periods whilst continuously chewing standard laboratory dry pellets or pieces of carrot and, in some animals, a mash of pellets with water. Flow was measured using contact drop recorders or a continuous flow recorder via Polythene tubes permanently inserted into one or both parotid ducts. Large variations in flow were obtained with unilateral recordings particularly during dry pellet chewing. Bilateral recordings showed that the flow was always greater on one side than on the other and that dominant secretion alternated from side to side in an apparently random manner. Rabbits chew unilaterally. Videotaped recordings of chewing movements showed that the greater secretion was always produced on the chewing side. To test the possibility that drying of the oral mucosa, or the prolonged hardness of the pellets may result in higher flow rates in animals with cannulated ducts than would normally be seen in intact animals, water was injected downstream into the mouth through a third cannula. This was inserted in an anterograde direction in the parotid duct on one side. Significant reductions in flow were recorded during dry pellet eating, but not during carrot eating. When animals were fed a soft pellet mash, salivary flow was significantly lower than with dry pellets. Recordings have been made from strain gauges attached to the ascending ramus of the mandible. Previous findings that dry pellets produce greater strain than carrots have been confirmed. It has also been shown that less strain is produced with soft pellet mash. The strain gauge data suggested that a relation exists between masticatory force and parotid salivary flow. The results are compatible with the hypothesis that intra-oral mechanoreceptors may be involved in a masticatory-salivary reflex. PMID- 4032297 TI - Interactions between motor units and Golgi tendon organs in the tibialis posterior muscle of the cat. AB - The responses of Golgi tendon organs to single motor unit contractions were studied to determine whether receptors located in the same muscle region respond to a common set of motor units. In each of five experiments we isolated a large fraction (25-65%) of the motor units of the cat tibialis posterior muscle and determined to which of the units each of several tendon organs was responsive. Each tendon organ was excited by from two to fifteen of the isolated motor units, including units which produced very small forces. However, there was a much greater probability for large force units to excite a given receptor than for small force units to do so. The number of motor units which produced either an 'unloading' or an 'off response' exceeded, on average, the number of motor units which excited the same tendon organ. The extent to which single motor units excited both of a pair of tendon organs was examined statistically in relation to the mutual proximity of the receptors within the muscle. It was found, on average, that the closer were two receptors, the greater was the number of motor units that excited both of them. These results suggest that despite the extensive territories of individual motor units, the spike trains of tendon organs may still encode information about localized muscle activity. PMID- 4032298 TI - Secretion of p-aminohippurate by the rat epididymis. AB - Secretion of p-aminohippurate (PAH) from blood into the sperm-free lumen of the rat cauda epididymidis was studied by a stop-flow luminal perfusion technique. After an intravenous injection of [3H]PAH, radioactive material with chromatographic properties similar to those of free PAH appeared in perfusates. The highest concentration of PAH reached in the lumen was about 3 times that of the free PAH in blood. This was achieved after equilibration of the epididymis with perfusate for 20 min. Luminal accumulation of PAH by the epididymis was inhibited by intravenous injection of probenecid (32 mg/kg). However, deprivation of androgens by castration for 21 days had no effect on secretion. The rate of secretion (from blood to lumen) of PAH altered in a non-linear fashion with the concentration of free PAH in the blood and showed saturation at a free blood concentration of about 4 mumol/l. The apparent Km and Vmax values were 2 mumol PAH/l blood and 0.2 mumol PAH/h. 20 cm tubule, respectively. Based on the concentration profile of PAH across epididymal cells, a model was proposed for the secretion of PAH. It is concluded that the secretory mechanism is similar to that of the renal tubule. The significance of these results was discussed in relation to the functions of spermatozoa in the male reproductive tract. PMID- 4032299 TI - Cutaneous receptive field and morphological properties of hamstring flexor alpha motoneurones in the rat. AB - Intracellular recordings have been made from twenty antidromically identified posterior biceps femoris/semitendinosus (p.b.s.t.) hamstring flexor alpha motoneurones in the decerebrate-spinal rat. The hamstring motoneurones had either low or no spontaneous background activity. In nineteen of the twenty cells high frequency phasic responses could be elicited by stimulation of the ipsilateral hind paw with firm pressure or pinch. There was no response to light touch or brush. Contralateral cutaneous mechanoreceptive fields with higher thresholds and weaker responses were present in 70% of the motoneurones. Noxious heating of the ipsilateral hind paw produced excitatory responses in six of eight cells tested and two of these cells also responded to heating of the contralateral hind paw. Stimulation of the ipsilateral sural nerve at graded strengths that successively activated A beta, A delta and C afferents produced excitatory post-synaptic potentials (e.p.s.p.s) at progressively longer latencies in the motoneurones. The C-fibre induced e.p.s.p. lasted up to 200 ms. Horseradish peroxidase was injected into ten motoneurones and in seven cases full reconstructions of dendritic field, cell body and axon could be made. In agreement with previous reports from studies in the cat, the dendritic fields of rat motoneurones are very extensive in the rostrocaudal, mediolateral and dorsoventral planes. The general pattern of dendritic branching for each motoneurone in this functionally homogeneous population was uniformly organized. Three major spatial orientations were always present: a rostrocaudally restricted series of dendrites emerging from the cell body and directed dorsolaterally towards the dorsolateral funiculus with branches in the lateral dorsal horn, a laterally, and a ventromedially directed series of branches arranged obliquely in the ventral horn, both of which were distributed rostrocaudally for equal distances from the cell body. Many of these dendritic branches terminated within the lateral and ventral white columns. Although the sizes of the rat flexor motoneurones' somas (51 +/- 4.9 micron, S.E., n = 10) were similar to those of cat lumbosacral alpha-motoneurones, the tip-to-tip rostrocaudal extent of their dendritic fields (1130 +/- 34 micron, S.E., n = 7) was half that reported in the cat. These results are discussed in terms of the organization of the cutaneous flexor withdrawal reflex in the rat. PMID- 4032300 TI - Measurement of net transplacental transfer of fluid to the fetal sheep. AB - If fetal drinking activity is prevented and it is assumed that in the latter third of gestation the fetus is capable of maintaining itself in fluid balance, then the net amount of fluid gained across the placenta by the fetus is equal to the amount of fluid lost from the fetus, by routes other than the placenta, plus fluid deposited in growing tissues minus the amount of water produced as a result of oxidative metabolism. Net transplacental transfer of fluid to the fetus over a 3 h period was measured in eight chronically catheterized fetal sheep in which drinking activity was prevented by ligating the oesophagus. Urine and lung liquid flow rates were measured. In the latter third of gestation, these are the only significant sources of fluid loss from these fetuses during the 3 h experimental period. Water produced as a result of oxidative metabolism was calculated, as was the amount of fluid deposited in growing tissues during the course of the experiment. The weight of the fetus at the beginning of the experiment and the change in weight that occurred during the experiment was calculated by measuring the weight of the fetus at death (within 30 h) and applying an equation which describes the body weight-gestation age relationship for merino sheep. Net transplacental fluid transfer was 0.40 +/- 0.09 ml min-1 kg-1 (range 0.30-0.54 ml min-1 kg-1). Fetal urine flow rate averaged 0.30 +/- 0.11 ml min-1 kg-1. It was 72.8 +/- 10.0% of the volumes used to calculate net transplacental fluid transfer to the fetus. Lung liquid flow rate was 0.079 +/- 0.039 ml min-1 kg-1. It was 20.2 +/- 9.2% of the volumes used to calculate net fluid intake. The amount of fluid deposited as a result of tissue growth was 0.023 +/- 0.001 ml min-1 kg-1; it was 5.94 +/- 1.1% of the volumes used in the equation, while the production of water as a result of metabolism was 3.9 X 10(-3) ml min-1 kg-1 (Conrad & Faber, 1977) and constituted 1.01 +/- 0.22% of the volumes used in the equation. This method of measuring net transplacental fluid transfer to the fetus can be used to measure fetal fluid intake over relatively short periods of time. It also means that the effects of disturbances in maternal fluid and electrolyte balance on fluid transfer to the fetus can be studied and quantitated. PMID- 4032301 TI - Activation of enteric nerve pathways in the guinea-pig duodenum by cholecystokinin octapeptide and pentagastrin. AB - The action and mechanism of action of cholecystokinin octapeptide (CCK-8) and pentagastrin on isolated segments of guinea-pig duodenum were examined using contractility studies and by intracellular recordings made from smooth muscle cells. Both CCK-8 and pentagastrin caused an excitatory contractile response. The threshold concentration ranged from 5 X 10(-11) to 10(-9) M for CCK-8 and 5 X 10( 10) to 10(-8) M for pentagastrin. The excitatory response was abolished by tetrodotoxin (3.1 X 10(-6) M) and atropine (1.5 X 10(-6) M) and inhibited by d tubocurarine (up to 2.9 X 10(-5) M). In the presence of atropine a proportion of preparations relaxed in response to CCK-8 (nineteen of thirty-one) and pentagastrin (thirteen of seventeen). This response was only seen at high concentrations of the peptides (10(-8)-10(-7) M) and was abolished by tetrodotoxin (3 X 10(-6) M). Intracellular recordings from duodenal smooth muscle revealed multiple excitatory junction potentials (e.j.p.s) in response to CCK-8 and to pentagastrin. These e.j.p.s were identical to those evoked by transmural nerve stimulation and were abolished by atropine (1.5 X 10(-7) M) and by tetrodotoxin (3 X 10(-6) M). Inhibitory junction potentials (i.j.p.s) were not recorded in response to the peptides except on one occasion. It is suggested that CCK-8 and pentagastrin cause an increase in duodenal motility by the selective activation of excitatory pathways in the enteric nervous system. PMID- 4032302 TI - The mechanism of the increase of tonic tension produced by caffeine in sheep cardiac Purkinje fibres. AB - The effects of caffeine were examined on contraction and membrane current in voltage-clamped sheep cardiac Purkinje fibres. The photoprotein aequorin was injected into several cells in order to measure the intracellular ionized Ca concentration [( Ca2+]i). When the Na-K pump was inhibited, depolarization produced a twitch followed by a tonic component of tension. Repolarization produced an after-contraction. These components of tension were accompanied by corresponding increases of aequorin light. Caffeine (10 mM) decreased both the twitch and the after-contraction while increasing the tonic component. The application of caffeine also produced a transient increase of aequorin light, both during depolarization and at rest, which was followed by a maintained decrease in all three components of the light signal. In particular, although caffeine decreased the rise of aequorin light during prolonged depolarization it increased the tonic tension. The possibility that the effects of caffeine on tonic tension could be due to suppression of spontaneous Ca oscillations was rejected for the following reasons. (i) Ryanodine (which also abolishes Ca oscillations) decreased the magnitude of the tonic tension. (ii) Caffeine still increased tonic tension when it was added to a fibre exposed to ryanodine (1-10 microM). In the presence of ryanodine it was possible to measure [Ca2+]i and tonic tension without interference from Ca oscillations. The increase of tonic tension produced by caffeine could not be accounted for by a rise of [Ca2+]i. The results showed that, at a given level of Ca, caffeine increased tension. The results show that a large part of the increase of tonic tension produced by caffeine is due to an increase of the Ca sensitivity of the contractile apparatus rather than to changes of [Ca2+]i. The consequence of this observation for the experimental use of caffeine is discussed. PMID- 4032303 TI - A dual mechanism for intracellular pH regulation by leech neurones. AB - Neutral-carrier pH-sensitive micro-electrodes were used to investigate intracellular pH (pHi) in leech neurones. When used in snail neurones such electrodes gave very similar pHi values to those recorded simultaneously by recessed-tip glass micro-electrodes. Leech Retzius neurones superfused with a pH 7.4 HCO3--free physiological saline were found to have a pHi of 7.3, too high to be explained by a passive distribution of H+ or OH-. To investigate pHi regulation the pHi was decreased by one of three methods: by exposure to propionate, by adding and then removing NH4Cl or by exposure to CO2. Acidification by any method was followed by a recovery to normal pHi values within 15-20 min. In HCO3--free solutions, pHi recovery from acidification was blocked by removing external Na or by amiloride (2 mM). In solutions buffered with 2% CO2 and 11 mM-HCO3-, amiloride slowed but did not block pHi recovery. The anion exchange inhibitor SITS (4-acetamido-4'-isothiocyanato-stilbene-2,2' disulphonic acid) also slowed pHi recovery in the presence of HCO3-. In CO2/HCO3- solution the removal of external Na either slowed or blocked pHi recovery, and blocked it completely in the presence of amiloride. We conclude that in HCO3- free solutions pHi regulation is by a Na-H exchange system; but in the presence of HCO3- there is an additional mechanism which is probably a Na-dependent Cl HCO3 exchanger. PMID- 4032304 TI - The mechanical properties of ciliary bundles of turtle cochlear hair cells. AB - The mechanical behaviour of the ciliary bundles of hair cells in the turtle cochlea was examined by deflecting them with flexible glass fibres of known compliance during simultaneous intracellular recording of the cell's membrane potential. Bundle motion was monitored through the attached fibre partially occluding a light beam incident on a photodiode array. The change in photocurrent was assumed to be proportional to bundle displacement. For deflexions of 1-100 nm towards the kinocilium, the stiffness of the ciliary bundles was estimated as about 6 X 10(-4) N/m, with the fibre attached to the top of the bundle. When the fibre was placed at different positions up the bundle, the stiffness decreased approximately as the inverse square of the distance from the ciliary base. This suggests that the bundles rotate about an axis close to the apical pole of the cell and have a rotational stiffness of about 2 X 10(-14) N. m/rad. Step displacements of the fixed end of the flexible fibre caused the hair cell's membrane potential to execute damped oscillations; the frequency of the oscillations in different cells ranged from 20 to 320 Hz. Displacements towards the kinocilium always produced membrane depolarization. The amplitude of the initial oscillation increased with displacements up to 100 nm and then saturated. For small displacements of a few nanometres, the hair cell's mechanoelectrical sensitivity was estimated as about 0.2 mV/nm. Force steps delivered by the flexible fibre caused the bundle position to undergo damped oscillations in synchrony with the receptor potential. The mechanical oscillations could be abolished with large depolarizing currents that attenuated the receptor potential. When placed against a bundle, a fibre's spontaneous motion increased and became quasi-sinusoidal with an amplitude several times that expected from the compliance of the system. It is suggested that the hair bundle drives the fibre. We conclude that turtle cochlear hair cells contain an active force generating mechanism. PMID- 4032305 TI - Development of synaptic currents in immobilized muscle of Xenopus laevis. AB - The effect of chronic immobilization on the development of synaptic currents was studied in myotomal muscle of Xenopus laevis. Embryos and tadpoles were immobilized by rearing them in the presence of tetrodotoxin (TTX) after removal of the egg membranes. Immobilization did not affect the developmental change in duration of miniature end-plate currents (m.e.p.c.s). Rise times decreased from about 3 to 0.6 ms in both immobilized and control muscle, and decay constants decreased from about 7 to 1 - 2 ms in both conditions. M.e.p.c.s with double exponential decays were recorded in both immobilized and control muscle at intermediate and late developmental stages. The fast and slow decay constants were 0.7 ms and slightly less than 3 ms in older muscle of both groups. These values are comparable to the apparent open times of fast and slow ACh receptors present on Xenopus muscle. Application of an anticholinesterase (methanesulphonyl fluoride) lengthened the duration of m.e.p.c.s comparably in immobilized and control muscle. These data indicate that the deposition of junctional acetylcholinesterase and the reduction in open time of acetylcholine receptor channels in developing Xenopus myotomal muscle are independent of contractile activity of muscle and TTX-blockable action potentials in muscle or motoneurones. PMID- 4032306 TI - Mucosal responses evoked by stimulation of ganglion cell somas in the submucosal plexus of the guinea-pig ileum. AB - The effects of electrical field stimulation and tetrodotoxin on the mucosal secretory response were compared in guinea-pig ileal mucosa with and without the submucosal plexus. Short-circuit currents and transmural electrical potential differences were similar in ganglionated and aganglionated tissues. Total tissue conductance was greater after removal of the submucosal ganglia. Electrical field stimulation evoked a tetrodotoxin-sensitive increase in short-circuit current in ganglionated tissues, and little or no response in aganglionated tissues. Both ganglionated and aganglionated tissues responded similarly to carbachol, vasoactive intestinal polypeptide, scorpion venom and alanine. These results suggest that electrical field stimulation of guinea-pig ileum evokes an increase in short-circuit current that reflects chloride secretion by exciting ganglion cell bodies whose axons project to the transporting cells and/or endocrine cells. Direct electrical activation of enteroendocrine cells is not a factor in the stimulus-evoked secretory response. PMID- 4032307 TI - Selective block of Y optic nerve fibres in the cat and the occurrence of inhibition in the lateral geniculate nucleus. AB - A method of selectively blocking the larger nerve fibres in the optic nerve of the cat is described. The optic nerve is compressed between a small balloon and the inside of a small metal cylinder. The block is monitored by stimulating and recording on opposite sides of the blocked region. The t1 (Y) response can be eliminated usually with some loss of the t2 (X) response. Stimulation of the blocked optic nerve initially excites certain cells (r2 or X) in the dorsal lateral geniculate nucleus (d.l.g.n.) but this is followed by an inhibition of both r1 (Y) and r2 (X) cells. This inhibition is similar in time course to that produced by stimulation of t1 fibres, suggesting that the effect may be mediated via a similar mechanism. The effect is present in a preparation in which all t1 fibres have degenerated, removing the possibility that it might have been due to inadvertent stimulation of t1 fibres. Experiments on a small number of r2 (X) d.l.g.n. cells have confirmed the inhibitory effect of stimulation of the smaller optic nerve fibres on X cells. PMID- 4032309 TI - Electromyographic activity in the cross-reinnervated soleus muscle of unrestrained cats. AB - Electromyographic (e.m.g.) activity was recorded from cross- and self reinnervated soleus and extensor digitorum longus (e.d.l.) muscles of the cat during normal activity, including standing, walking and jumping. Activity patterns of normal soleus, e.d.l., and lateral gastrocnemius (l.g.) were essentially similar to those shown by other investigators. The self-reinnervated soleus fired phasically and synchronously with l.g. during walking but the activity was not trimmed to the extent that is seen in normal soleus. This is attributed to the relatively limited amount of proprioceptive information arising from such muscles. The activity pattern of the cross-reinnervated soleus muscles was variable. During walking, the phase of activity was sometimes coincident with that of a normal e.d.l., at other times (even in the same animal) it would be approximately coincident with l.g. The phase of activity usually consisted of an initial burst which was not sustained. Reflex activity elicited from the cross reinnervated soleus was very similar to that of normal e.d.l., indicating the rigidity of connexions for reflex responses. reinnervated e.d.l. muscles; the activity attributable to the cross-reinnervated portion was similar to that seen in a self-reinnervated soleus. The activity pattern of soleus, reinnervated by the nerve to e.d.l. (an effective antagonist) is unlike that of either a normal soleus or e.d.l. muscle. This is attributed to a combination of lack of proprioceptive information and/or some degree of central remodelling. PMID- 4032308 TI - Differentiation of vasodilator and sudomotor responses in the cat paw pad to preganglionic sympathetic stimulation. AB - We monitored sweat secretion (using skin potential) and blood flow (using skin temperature) in the hind-paw skin of chloralose-anaesthetized cats pre-treated with guanethidine, and studied the responses to electrical stimulation of the ipsilateral lumbar sympathetic trunk. Stimulation caused sweat secretion and an increase in skin blood flow which was almost entirely restricted to the paw pads and was completely ipsilateral. Stimulation of the tibial nerve trunk produced similar effects, except that the increase in blood flow was more prolonged. The vasodilator effect of sympathetic trunk stimulation was not affected by chronic deafferentation of the paw. Atropine methonitrate (0.5-1 mg/kg I.V.) abolished the sudomotor response to sympathetic stimulation, but did not attenuate the blood flow response. Hexamethonium (1-2 mg/kg I.V.) abolished the vasodilator response to sympathetic stimulation, but did not affect the sudomotor response. Larger doses of hexamethonium (10-20 mg/kg) abolished both responses. The data suggest that the lumbar post-ganglionic neurones mediating vasodilatation in the skin of the cat paw pad are distinct from those that mediate sudomotor secretion. PMID- 4032310 TI - Respiratory modulation of muscle sympathetic and vagal cardiac outflow in man. AB - We studied the influence of respiration on muscle sympathetic and cardiac vagal activities in twenty conscious, healthy young adult subjects. Efferent post ganglionic muscle sympathetic activity was measured directly with electrodes inserted percutaneously into a peroneal nerve, and vagal cardiac activity was measured indirectly from electrocardiographic changes of heart period. Muscle sympathetic activity waxed and waned with respiration; maximum activity occurred at end-expiration and minimum activity occurred at end-inspiration. Voluntary control of breathing did not alter the time course or magnitude of muscle sympathetic outflow. Spectral analyses showed that respiratory periodicities were present in sympathetic and vagal records. Average power at frequencies below respiratory frequencies exceeded or equalled that at respiratory frequencies in both muscle sympathetic and vagal cardiac records. A cardiac periodicity was present and conspicuous in muscle sympathetic recordings in all but one subject. Diastolic arterial pressure increased during inspiration and decreased during expiration. Heart period and muscle sympathetic activity paralleled each other and were related reciprocally to changes of diastolic pressure. Brief reductions of carotid baroreceptor afferent traffic provoked by neck pressure were more effective in increasing sympathetic activity in expiration than inspiration. We conclude that quiet respiration is associated with parallel phasic changes in activity of medullary vagal cardiac and spinal muscle sympathetic motonuclei in man; spontaneous activity and susceptibility to excitation or inhibition by autonomic inputs are greater in expiration than inspiration. Substantial power is present in both muscle sympathetic and cardiac vagal recordings at frequencies below respiratory frequencies. PMID- 4032311 TI - Spinothalamic lumbosacral lamina I cells responsive to skin and muscle stimulation in the cat. AB - The response characteristics of lamina I neurones recorded extracellularly in the lumbosacral enlargement of chloralose-anaesthetized cats were examined with peripheral nerve electrical stimulation, adequate mechanical and thermal stimulation of hind-limb skin, and algesic mechanical and chemical stimulation of musculotendinous structures, particularly the gastrocnemius-soleus (g.s.) muscle. Antidromic activation from an electrode array that spanned the contralateral thalamus was used to identify lamina I spinothalamic tract (lam.I-s.t.t.) neurones. Recordings were made from a total of 218 lumbosacral lam.I-s.t.t. neurones. Their mean central conduction latency was 90.1 ms (range 20-300 ms), corresponding to a mean conduction velocity of 3.7 m/s (range 1.1-16.7). Neurones responsive only to peripheral A delta fibre stimulation had significantly shorter central conduction latencies (mean = 62.8 ms) than those with both A delta and C fibre input (mean = 81.9 ms) and those with only C fibre input (mean = 134.6 ms). Of these 218 neurones, 103 (47%) projected only to medial thalamus, 41 (19%) only to lateral thalamus, and 56 (26%) to both; 18 (8%) were classified as mid thalamic projecting cells. About 10% of all cells had ongoing activity when first isolated. Ninety-three lam.I-s.t.t. neurones responded to stimulation of the sciatic nerve. The response characteristics of forty-seven of these were examined with the complete set of stimuli used. Twenty-four non-s.t.t. lamina I neurones were also characterized for comparison. Twenty-eight of the lam.I-s.t.t. neurones tested with the complete set of stimuli responded specifically to either cutaneous noxious (n = 19), cutaneous innocuous cold (n = 6) or algesic musculo tendinous (n = 3) stimulation. Thirteen neurones responded to cutaneous noxious stimulation, and, in addition, to cold stimulation (n = 6), to deep stimulation (n = 4), or to both (n = 3). Six cells did not respond to any of the natural stimuli employed. All of the cold-specific and many of the multireceptive cold sensitive neurones had ongoing discharge. The average central conduction latencies of cold-sensitive neurones (65.5 ms) and unresponsive neurones (48.7 ms) were shorter than that of nociceptive neurones (91.2 ms). Two response categories had distinct thalamic projection patterns. The majority of cold specific neurones projected only to medial thalamus. Almost all multireceptive cold-sensitive neurones projected to both medial and lateral thalamus.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 4032312 TI - C-fibre excitation and tonic descending inhibition of dorsal horn neurones in adult rats treated at birth with capsaicin. AB - Single unit electrical activity has been recorded from dorsal horn neurones in the lumbar cord of rats anaesthetized with sodium pentobarbitone. Three groups of animals were used: normal adult rats, adult rats that had been treated at birth with capsaicin (50 mg kg-1 s.c.) and adult rats that had been injected at birth with the drug vehicle only. Rats treated at birth with capsaicin showed a substantial reduction in the number of afferent C fibres as indicated by the virtual absence of C waves in the compound action potentials evoked in the sural nerve by antidromic stimulation of the L4-L6 dorsal roots. No significant differences were found in any of the parameters measured between the vehicle treated and the untreated animals. Therefore, rats from these two groups are referred to as control animals. All dorsal horn neurones studied were driven by electrical stimulation of the A fibres in the ipsilateral sural nerve and had cutaneous receptive fields in the ipsilateral hind limb. Two groups of neurone were distinguished: those receiving an input from A fibres only (A only) and those neurones that could also be driven by sural C fibres (A + C). In the control group, 56% of the neurones were A only and 44% were A + C. In capsaicin treated rats these proportions were significantly different: 78% and 22% respectively. No differences were found in receptive field sizes of A-only neurones between those recorded in control rats and those from capsaicin-treated animals. However, a large and significant increase in receptive field size of A + C neurones was observed in capsaicin-treated rats compared to their counterparts in normal animals. In control rats 80% of the A + C neurones showed tonic descending inhibition of their C-fibre-evoked responses as assessed by reversible spinalization. In capsaicin-treated rats this proportion fell to 47% of the A + C neurones. The magnitude of the tonic descending inhibition was also reduced in the fewer A + C neurones of capsaicin-treated rats that were subjected to it. Only 4% of A + C neurones with tonic descending inhibition in capsaicin-treated rats were powerfully inhibited compared to 26% in control animals. The mean number of spikes evoked by C-fibre stimulation of the sural nerve in A + C neurones of control and of capsaicin-treated rats was not significantly different between these two groups of animals in the intact and in the spinalized states.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 4032313 TI - Activity-dependent excitability changes in normal and demyelinated rat spinal root axons. AB - Myelinated nerve fibres with a reduced safety factor for conduction due to demyelination are easily blocked by trains of impulses. To find out why, in vivo recordings from rat ventral root fibres demyelinated with diphtheria toxin have been supplemented with in vivo and in vitro recordings from normal fibres. Despite a small rise in extracellular potassium activity, normal fibres were invariably hyperpolarized by intermittent trains of impulses. This hyperpolarization resulted in an increase in threshold and also in an enhancement of the depolarizing after-potential and the superexcitable period. Replacement of NaCl in the extracellular solution by LiCl completely blocked both the membrane hyperpolarization and the threshold increase which were normally observed during intermittent trains of impulses. At demyelinated nodes which were blocked by trains of impulses (10-50 Hz), conduction block was preceded by a rise in threshold current and in an increase in internodal conduction time, but by no detectable reduction in the outward current generated by the preceding node. It was found possible to prevent the threshold from changing during a train by automatic adjustment of a d.c. polarizing current. This 'threshold clamp' prevented the conduction failure and virtually abolished the changes in internodal conduction time. The threshold changes were attributed to hyperpolarization, as in normal fibres, since (a) the polarizing current required to prevent them was always a depolarizing current, and (b) they were accompanied by an increase in superexcitability. The post-tetanic depression that can follow continuous trains of impulses was attributed to the combination of increased threshold and enhanced superexcitable period due to hyperpolarization. It is concluded that the susceptibility of these demyelinated fibres to impulse trains is not due to a membrane depolarization induced by extracellular potassium accumulation but to a membrane hyperpolarization as a consequence of electrogenic sodium pumping. PMID- 4032314 TI - Adaptation of mechanical properties of muscle to high force training in man. AB - The first dorsal interosseus muscle of the hand was trained for 8 weeks using eighty maximal 10 s voluntary isometric contractions per day. As a result of this training the maximal voluntary force increased by 33%, but electrically evoked tetanic tension increased by only 11%. In other subjects the muscle was trained using electrical stimulation at 60 Hz to evoke eighty maximal 10 s tetani per day for 8 weeks. This training produced no increase in maximum voluntary force. Our results show that the increase in maximal voluntary force under these conditions may be due to a change in the voluntary neural drive to the muscle. PMID- 4032315 TI - Effects of prior instruction and anaesthesia on long-latency responses to stretch in the long flexor of the human thumb. AB - Long-latency (40-80 ms) electromyographic (e.m.g.) responses of the contracting flexor pollicis longus to stretches applied at the thumb-tip, were studied in normal human subjects. Stretches were applied during four classes of contraction: (i) isometric 'hold', in which the subject held a steady isometric contraction; (ii) isometric tracking, in which the subject tracked a steadily rising force target; (iii) isotonic tracking, in which the subject flexed against a constant torque to track a position target; (iv) weight-lifting, in which the subject lifted a weight hung at one end of a lever by pressing the thumb-tip on the other end of the lever. The effects on the responses of prior instructions to 'resist' or to 'let go', and of local anaesthesia of the thumb, were studied. The ability to modify the size of the long-latency e.m.g. response in accordance with prior instruction was variable. All subjects tested could do so during isometric holding contractions, but many could not do so during the other forms of contraction. Local anaesthesia of the thumb significantly reduced the long latency e.m.g. response in only some subjects, and abolished it in none. The reduction was most reliably seen for isometric force tracking contractions. During thumb anaesthesia in different subjects, there was a significant correlation between the proportional increase in apparent heaviness of an object lifted by thumb flexion and the proportional reduction in the size of the long latency e.m.g. response to muscle stretch. PMID- 4032316 TI - Flow through the foramen ovale of the fetal and new-born lamb. AB - Right and left atrial pressures were measured in eight chronically instrumented fetal and neonatal lambs. Flows were measured with a combination of electromagnetic flow sensor and microsphere techniques. Three of the fetuses were ventilated in utero during the measurements. Four fetuses were studied as neonates immediately after spontaneous term delivery and one was studied as a normal fetus in utero. Data from these preparations were augmented with seven sets of previously reported data from normal fetuses in utero for analysis. Linear least-squares regression analysis demonstrated that inferior caval vein flow into the right atrium was inversely related to right atrial pressure. This flow could not be demonstrated to depend on the velocity of blood in the inferior caval vein. Non-linear least-squares regression analysis of foramen ovale flow as a function of a power of the flow in the inferior caval vein revealed that the square of the velocity of blood in the inferior caval vein predicted foramen ovale flow. Of the two forces that determine foramen ovale flow in the fetus, pressure difference and kinetic energy, the latter was far larger than the former. These results support the theory that the fetal foramen ovale is maintained in an open position by the kinetic energy of the blood in the inferior caval vein. PMID- 4032317 TI - Nervous control of mucin secretion into human bronchi. AB - Pieces of ferret trachea and human bronchi were mounted in Ussing chambers and given [35S]sulphate as a radiolabelled precursor of mucous glycoproteins (mucins). The output of 35S bound to macromolecules was studied as an index of mucin secretion. In the ferret trachea, electrical field stimulation increased the rate of mucin secretion. Tetrodotoxin (10(-7) M or 10(-6) M) abolished this effect. Pilocarpine (25 microM) stimulated the output of mucins from human bronchus. Atropine (10(-5) M) abolished this effect. Electrical field stimulation of human bronchus stimulated mucin secretion. Tetrodotoxin (10(-6) M) abolished this effect. Field stimulation in the presence of either atropine (10(-5) M) or atropine with l-propranolol (10(-5) M) and phentolamine (10(-5) M) caused no stimulation of mucin secretion rate. Some bronchi were treated with noradrenaline (10(-5) M) for 1 h to allow the adrenergic nerves to take up transmitter. Even in these, atropine prevented the effect of field stimulation. We conclude that activity in cholinergic nerves can stimulate mucin secretion in the bronchi in man. Our results provide no evidence that the adrenergic nerves or non adrenergic, non-cholinergic nerves have a direct action on bronchial secretory cells in man. PMID- 4032319 TI - [How does endogenous and exogenous cholesterol influence the lipoprotein metabolism. Effects of long-term endurance exercise, and accumulation of cholesterol ester on the aortic wall]. AB - We first supplied the rats with sucrose which accelerates the synthesis of the very low density lipoprotein (VLDL). After 5 weeks ingestion, we investigated the effects of the long-term endurance exercise on the concentration of the endogenous cholesterol and on the accumulation of the cholesterol ester on the arterial wall, with the emphasis on lipid metabolism, especially on lipoprotein metabolism. The concentrations of triglyceride and VLDL in sucrose-ingested group were significantly higher than control. As to the aortic wall, the total amount of cholesterol ester was increased (almost twice). Regular endurance exercise over long period after serum and hepatic lipids had already reached a high level did not reduced the triglyceride in the liver but in serum. It showed be emphasized that the exercise reduces triglyceride and VLDL-cholesterol, and to this extent does contribute to alleviation of hyperlipidemia and to prevention or moderation of arteriosclerosis. PMID- 4032318 TI - Spatial and temporal frequency selectivity of neurones in visual cortical areas V1 and V2 of the macaque monkey. AB - The spatial and temporal frequency selectivity of 148 neurones in the striate cortex, V1, and of 122 neurones in the second visual cortical area, V2, of the macaque monkey were studied using sine-wave gratings of suprathreshold contrast drifting over the receptive field at the preferred orientation and direction. Neurones in V1 and V2 were selective for different but partially overlapping ranges of the spatial frequency spectrum. At retinal eccentricities of 2-5 deg from the fovea, the spatial frequency preferences for neurones ranged from 0.5 to 8.0 cycles/deg in V1 and from 0.2 to 2.1 cycles/deg in V2 and were on average almost 2 octaves lower in V2 than in V1. Spatial frequency full band widths in the two cortical areas were in the range 0.8-3.0 octaves, with a mean value of 1.8 octaves, in the parafoveal representation of both V1 and V2, and 1.4 and 1.6 octaves respectively in the foveal representation of V1 and V2. Most neurones in V1 and some in V2 responded well at temporal frequencies up to 5.6-8.0 Hz before their responses dropped off at still higher frequencies. In V1, 68% of the neurones exhibited low-pass temporal tuning characteristics and 32% were very broadly tuned, with a mean temporal frequency full band width of 2.9 octaves. However, in V2 only 30% of the neurones showed low-pass temporal selectivity and 70% of the cells had bandpass temporal characteristics, with a mean full band width of 2.1 octaves. In V2 the minimal overlap of bandpass tuning curves across the temporal frequency spectrum suggests that there are at least two distinct bandpass temporal frequency mechanisms as well as neurones with low-pass temporal frequency tuning at each spatial frequency. A matrix of spatial and temporal frequency combinations was employed as stimuli for neurones with bandpass temporal frequency selectivity in both V1 and V2. The resultant spatio-temporal surfaces provided evidence that a neurone's preference for spatial frequency is essentially independent of the test temporal frequency; however, in V2 there was some tendency for temporal frequency peaks to shift slightly towards lower frequencies when non-optimum values of spatial frequency either above or below the preferred value were tested. Neurones with pronounced directional selectivity were encountered over a wide range of spatial frequencies, although in both cortical areas there was a tendency for an increased incidence of directional selectivity among neurones which were selective for lower spatial frequencies and higher temporal frequencies. PMID- 4032320 TI - [Correlation of subjective assessments with somatosensory evoked potentials to electrical stimulation of the finger in man]. AB - The relationship between 5 positive components of somatosensory evoked potentials (EPs) and subjective response to electrical stimuli, which were recorded in the same human subjects, was assessed in the present study. Five levels of tactile stimuli and 6 levels of noxious stimuli were applied to the tip of the right index finger. The relationship between the magnitude of subjective response and stimulus intensity was well expressed by a power function. Of 5 major positive components in an EP, P30 and P50 were localized at contralateral primary somatic projection area, while P90, P190 and P270 were at the vertex area. The amplitude of the 5 components systematically increased as increasing stimulus intensity, and also increased with the magnitude of subjective response. A significant correlation between the amplitude of P30 or P50 and stimulus intensity was found when the effect of subjective response was partially out. By contrast, the amplitudes of P190 and P270 were associated with subjective response when the effect of stimulus intensity was partially out. These results suggest that the earlier EP components reflect sensory signal processing, while the latter ones concern the subjective evaluating system. PMID- 4032321 TI - [Somatosensory evoked potentials and pain discrimination in man]. AB - The relationship between 10 components of somatosensory evoked potentials (EPs) and pain discrimination in man was studied using Signal Detection Theory (SDT) psychophysics. Two painful electrical stimuli were delivered to the right index finger in random order over all trials. EPs were recorded from the scalp at the contralateral primary somatic projection area while subjects performed SDT discrimination. The stimulus-response combination was classified into 4 categories according to SDT response: hits, misses, false alarms (FAs) and correct rejections (CRs). The amplitudes and peak latencies of EPs in 4 categories were compared with each other. EPs associated with hits and FAs had significantly greater amplitude at P 190, N 220 and P 270 than those associated with misses and CRs, while there was no change in the amplitude of other components. The amplitude of these 3 components systematically increased with an increase in the magnitude of subjective response. Peak latencies of all components were not related to the response categories. These results indicate that the amplitude of the 3 last components may be concerned with the pain evaluating system in the brain. PMID- 4032322 TI - Vocal cues to deception: a comparative channel approach. AB - The study investigated the leakage potential of different voice and speech cues using a cue isolation and masking design. Speech samples taken from an earlier experiment were used in which 15 female students of nursing dissimulated negative affect produced by an unpleasant movie or told the truth about positive affect following a pleasant movie. Several groups of judges rated these speech samples in five conditions: (1) forward or clear, (2) electronic filtering, (3) random splicing, (4) backwards, (5) pitch inversion, (6) tone-silence sequences. The results show that vocal cues do indeed carry leakage information and that, as reflected in the differences among the conditions masking different types of cues respectively, voice quality cues may be centrally implicated. In addition, gender differences in decoding ability are discussed. PMID- 4032323 TI - Cardiovascular and electrodermal adjustments during a vigilance task in patients with borderline and established hypertension. AB - We studied cardiovascular and noncardiovascular sympathetic nervous system (SNS) responses to a vigilance task in patients with borderline (BT) or established hypertension (HT). Twelve patients in each group and twelve normotensive controls (NT) were subjected to a signalled reaction-time (RT) task which included the presentation of a noxious 110 dB white noise contingent upon RT-performance at the end of a 30 sec foreperiod. During this foreperiod recordings were made of: systolic and diastolic blood pressures, heart rate, skin- and muscle-blood flows. Skin and muscle vascular resistances were calculated from mean blood pressure and regional blood flows. Skin conductance level, fluctuations and responses were recorded as noncardiovascular SNS-responses. Compared to NT both HT and BT had higher resting blood pressures, heart rate, skin- and muscle-vascular resistances. BT showed higher resting skin conductance levels than HT and NT who were not different from one another. During stimulation HT and BT evidenced pressor hyperreactivity compared to NT. The electrodermal effects did not parallel the cardiovascular ones. Skin conductance and cardiovascular variables were more closely related in NT than HT or BT. The presence of cardiovascular hyperreactivity together with the absence of noncardiovascular hyperreactivity in HT indicates heightened SNS-activity specific to the cardiovascular system and not part of generalized SNS-arousal. The similarity between HT and BT is consistent with the notion that the differences between BT and HT are quantitative rather than qualitative. PMID- 4032324 TI - A study of brief psychotherapy for chronic pain. AB - Twenty-six patients attending the pain clinic of a large metropolitan general hospital were randomly assigned to receive either twelve sessions of psychodynamic psychotherapy or six sessions of cognitively orientated supportive psychotherapy. Questionnaires measuring aspects of illness behaviour, depression and anxiety were administered before and after treatment, but did not reveal any significant differences between the treatment groups at any time. Global subjective estimates of outcome reported to an independent observer were made after completion of therapy and showed no significant differences. All measures were repeated six and twelve months after completion of therapy and revealed significant improvement in the dynamic therapy group only with respect to levels of activity. These findings suggest that brief psychodynamically oriented psychotherapy may have a role in the management of chronic pain but further evaluation of this approach is clearly necessary, involving larger numbers of patients, before a more definitive conclusion can be reached. PMID- 4032325 TI - Development of a brief self-report measure of the type A (coronary prone) behavior pattern. AB - This study reports the development of a brief self-report measure of the Type A behavior pattern based upon a set of adjectives derived from the Gough Adjective Checklist (ACL). Previous work from our laboratory established a set of adjectives identified by experts as being relevant to the Type A construct that subsequently was found to successfully distinguish Type A individuals from their Type B counterparts. In the present study, a Type A self-rating scale based on these adjectives was found to be significantly related to an established Type A self-report instrument, the Jenkins Activity Survey (JAS), and to an independent behavioral rating based upon a standard structured interview (SI). However, no measure of Type A was related to the severity of coronary artery disease (CAD) as documented by coronary angiography. The advantages and disadvantages of the various Type A measures are discussed in the context of their ability to identify individuals at risk for the development of CAD. PMID- 4032326 TI - Effects of general and thematically relevant stressors in Raynaud's disease. AB - Emotional stress has been reported to cause vasospastic attacks in some patients with idiopathic Raynaud's disease. In the present study, the physiological and subjective responses of 32 Raynaud's disease patients and 22 normal subjects to three imagined scenes were compared. Both groups responded similarly to a neutral and a generally stressful scene. However, a scene having content thematically relevant to Raynaud's disease produced decreased finger temperature in these patients but not in normal controls. These findings are discussed in terms of stimulus specificity and social learning theories. PMID- 4032327 TI - Somatic illness in manic-depressive and schizophrenic patients. AB - The study compared the presence of somatic illnesses in manic-depressive (n = 100) and schizophrenic patients (n = 156) in the out-patient psychiatric clinics of three general hospitals. The average age of manic-depressive and schizophrenic patients was 40.7 yr and 39.8 yr respectively and did not differ significantly. The sample consisted of both sexes. Among the manic-depressive patients there were 46 males and 54 females. The schizophrenic sample consisted of 84 (54%) males and 72 (46%) females. The result showed that there was a greater rate of the occurrence of physical illnesses in manic-depressive patients as compared to the schizophrenic patients in respect to all the surveyed systemic disorders except for the gastrointestinal diseases. The cardiovascular, neurological and endocrinological diseases were more frequent in the manic-depressives than in the schizophrenic patients. PMID- 4032328 TI - Psychophysiological evidence for a state theory of hypnosis and susceptibility. AB - Psychophysiological evidence is presented of altered cerebral organisation under hypnosis. Bilateral electrodermal activity was examined to tones presented simultaneously with the induction of hypnosis. Susceptibility was monitored throughout. Two control conditions were devised, one for division of attention and another for relaxation. In addition there was a familiarisation session which permitted groups to be equated for rates of habituation. Both faster and slower habituation were found under hypnosis but the direction of change related to susceptibility; Susceptible subjects showed a reduction in orienting responses and Unsusceptible subjects an increase in responses. Susceptible subjects also had lower tonic levels of activity and fewer nonspecific responses during the induction prior to the tones. Neither relaxation nor listening to a story altered habituation systematically. Under hypnosis there was a reversal in lateral asymmetries in orienting response amplitudes in Susceptible subjects suggesting a shift in hemispheric influences from left to right. PMID- 4032329 TI - Simultaneous recording of penile diameter and penile arterial pulse during laboratory-based erotic stimulation in normal subjects. AB - We have assessed erectile responses of normal male subjects to short periods of fantasy and to short erotic films, using simultaneous measurement of penile diameter and penile dorsal arterial pulse amplitude, together with systemic arterial blood pressure, heart rate and skin blood flow. By a variety of criteria, we have satisfied ourselves that penile pulse amplitude reflected local vascular changes in the penis rather than changes in systemic blood pressure, although it is uncertain whether it was primarily determined by the magnitude of arterial flow or that of arterial volume. Penile pulse amplitude usually increased markedly during the stimulation period, and was correlated with penile erection. The temporal relationship between these two parameters was variable. Typically pulse amplitude increase started later than diameter increase but thereafter changed in parallel. In a proportion of responses, however, these two changes were markedly dissociated in time and these responses tended to be slower in reaching their maximum diameter. This variable association suggests that two separate processes involved in erection are being measured. Simultaneous monitoring of penile diameter and penile pulse may therefore provide further information about the basic physiological processes involved in penile erection as well as diagnostic information in patients with erectile dysfunction of uncertain aetiology. PMID- 4032330 TI - Assessment of erectile function in diabetic and non-diabetic impotence by simultaneous recording of penile diameter and penile arterial pulse. AB - Simultaneous monitoring of penile diameter and penile arterial pulse during laboratory-based erotic stimulation with film and fantasy, has been used to compare diabetic and non-diabetic impotent men with non-impotent controls. The degree of erection to erotic film distinguished between organic and psychogenic aetiologies. The diabetic group showed smaller penile pulse amplitude changes than the other two groups. Amongst the diabetics, severe autonomic neuropathy was associated with impaired erectile and penile pulse amplitude responses. Severe retinopathy was associated with smaller baseline penile pulse amplitude as well as smaller amplitude response. Blood pressure response to erotic stimuli did not differ between the three groups. An analysis of the temporal relationship between penile diameter change and pulse amplitude change revealed differences between the groups that may prove to have diagnostic as well as theoretical implications. PMID- 4032331 TI - Psychometric ante-natal predictors of post-natal depressed mood. AB - One hundred and nine women were studied during the course of pregnancy in an attempt to predict which of them would later rate themselves as suffering from depressed mood up to twelve months post-natally. The psychometric measures used comprised the Zung Self-Rating Scale to measure depression, the DSSI/SAD sub scale to measure anxiety and the Hostility and Direction of Hostility Questionnaire. Post-natal depression observed up to twelve months post-partum was positively associated with first trimester ante-natal scores on all three measures. The HDHQ and the DSSI/SAD measures were good predictors of depression at six weeks post-partum and both correlated significantly at six and nine months post-partum, whereas the Zung measure predicted depression at nine and twelve months as well as at six weeks post-partum. Parity was significantly associated with severe depression at six months post-partum. PMID- 4032332 TI - San Carlos to Port Stanley or one way to spend Christmas down-under. PMID- 4032333 TI - Tirich Mir 1984. PMID- 4032334 TI - The British Association for Immediate Care (BASICS). PMID- 4032335 TI - Medical contingent, Diego Garcia. PMID- 4032336 TI - The Society for Nautical Research. PMID- 4032337 TI - Routine Pulheem assessments. PMID- 4032338 TI - Arctic Survival Training--Norway 1985. PMID- 4032339 TI - Excessive lateral pressure as a cause of patello-femoral pain syndrome. PMID- 4032340 TI - Primary (non-carcinoid) adenocarcinoma of the vermiform appendix--an unexpected finding following appendicectomy. PMID- 4032341 TI - Torsion of the testis occurring during a Polaris patrol. PMID- 4032342 TI - Four cases of spinal cord compression: the need for early diagnosis. PMID- 4032343 TI - [Disk calcifications in children]. AB - It is not unusual for intervertebral disk calcifications to be detected in pediatric practice, the 150 or so cases reported in the literature probably representing only a small proportion of lesions actually diagnosed. Case reports of 33 children with intervertebral disk calcifications were analyzed. In the majority of these patients (31 of 33) a diagnosis of "idiopathic" calcifications had been made, the cervical localization of the lesions being related to repeated ORL infections and/or trauma. A pre-existing pathologic factor was found in two cases (one child with juvenile rheumatoid arthritis treated by corticoids and one child with Williams and Van Beuren's syndrome). An uncomplicated course was noted in 31 cases, the symptomatology (pain, spinal stiffness and febricula) improving after several days. Complications developed in two cases: one child had very disabling dysphagia due to an anteriorly protruding cervical herniated disc and surgery was necessary; the other child developed cervicobrachial neuralgia due to herniated disc protrusion into the cervical spinal canal, but symptoms regressed within several days although calcifications persisted unaltered. These findings and the course of the rare complications documented in the literature suggest the need for the most conservative treatment possible in cases of disc calcifications in children. PMID- 4032344 TI - [X-ray computed tomography in fractures of the acetabulum]. AB - Radiographic assessment of these fractures remains difficult. Conventional techniques according to Letournel show the lesions but not to the best advantage, for instance the "congruency" of femoral head with acetabulum. 54 CT scan were performed (1982-1984) every time a doubt was persisting. Incarcerations of fragments, impactions of the acetabulum, sacro-iliac joint disjunctions, congruency and lesions of femoral head are much better seen with scanner. In planing the surgical therapy (or orthopedic), CT scan add a great deal to the information and dramatically improves the results. PMID- 4032345 TI - [Lateral radiculography in the vertical position for the diagnosis of narrow lumbar canal]. AB - Results obtained in 66 cases emphasize the value of lateral imaging to increase sensibility of radiculography in the diagnosis of narrow lumbar canal. In all cases, in fact, the anteroposterior diameter of the opacified canal diminished in the standing position in proportions varying from 20 to 50%, and furthermore, in 20% of patients diagnosis was only possible from this image. Narrowing of the canal was considered as being present in patients with an anteroposterior canal diameter in the standing position that was less than 11 mm in corrected values. This image appears therefore to be an essential one, particularly as clinical symptomatology of narrow lumbar canal is very often atypical (62% of cases). Moreover, contrary to widespread opinions, computed tomography is sometimes less sensitive than radiculography in this type of disorder. PMID- 4032346 TI - [Plate thermography in the evaluation of idiopathic carpal canal syndrome. Apropos of 32 cases]. AB - During a period of eight months thirty-two cases (twenty-two unilateral and five bilateral) of idiopathic carpal tunnel syndrome were studied at the Saint-Louis Hospital, Paris, France. The patients were found to benefit from the use of the preoperative technique, thermography in addition to routine clinical exams and complementary exams such as radiographs and E.M.G. The period of intervention was from the fifteenth day through the second and thirds months. By comparing the clinical and functional results before and after surgical treatment through the use of images from patients in the same condition, it can be concluded that the use of this simple technique can provide valuable information and is harmless in the care of idiopathic carpal tunnel syndrome. It is demonstrated that thermography permits: the ability to foresee the action of treatment; the ability to survey the effects of treatment and therefore obtain a valuable prognosis; and finally, a method of deciding on other acrosyndromes. PMID- 4032347 TI - [Primary esophageal localization of non-Hodgkin's lymphoma. Apropos of a case]. AB - Authors present a case of primary oesophageal lymphoma, in view of the great rarity of the neoplasm in this place. PMID- 4032348 TI - [Hemangioma of the pancreas]. AB - A 62 year old woman lacking any alteration in her general condition and without digestive disorders was found fortuitously to have a large mass in the epigastric region. Complementary investigations localized the lesion to the peritoneal cavity, either in the gastrocolic omentum or the mesentery, close to the pancreas. Imaging showed a multicystic heterogeneous structure. A large hemangioma of pancreatic origin was removed at operation. PMID- 4032349 TI - [Results of in situ arterial thrombolysis by the combination of urokinase and lysyl plasminogen in acute arterial occlusive diseases of the lower limbs]. AB - 35 patients with acute arterial occlusions [27] and graft thromboses [8], responsible for severe and recent ischemia, were treated by fibrinolytic therapy (Urokinase: 1 000 units/kg/hour, and Lys Plasminogen). These drugs were delivered at the site of occlusions using a 5 French catheter. Angiographically, initial success was obtained in 30 patients (85%) and a significant clinical benefit persisted 5 months later, in 20 patients (57%). 4 distal embolisms during the treatment were noted, and one woman died a few hours after the withdrawal of an axillary catheter of a cerebellar infarction. Only two minor (6%) and one severe (3%) groin hematoma were encountered. No patient had at any moment a fibrinogen concentration lower than 1 g/l. Thus, the thrombolytic treatment used in the study appears as effective as locally administered Streptokinase but better tolerated. PMID- 4032350 TI - [Contrast agents in magnetic resonance imaging]. AB - The origin of nuclear magnetic resonance signal is reminded in this paper. Different ways of increasing the contrast in magnetic resonance imaging are presented, especially modifications of tissues relaxation times by the use of paramagnetic ions or nitroxides. The potential of these substances is illustrated by several examples of application in the animal. PMID- 4032352 TI - Clinical judgement. PMID- 4032351 TI - The spread of type A influenza. PMID- 4032353 TI - Interpretation of diagnostic data: an unexplored field in general practice. AB - In interpreting diagnostic information the differences between morbidity patterns in general practice and those in hospitals must be taken into consideration. This article demonstrates the importance of prevalence for predictive values of complaints, symptoms and test results. When the general practitioner refers patients to the specialist, these values may change, and it is also possible that associations between symptoms and diagnoses are distorted by selection bias. Moreover, attention must be paid to the differences in clinical stages encountered in general practice and specialist practice. It is concluded that a large part of the ;diagnostic field' of general practice has still to be discovered and developed. PMID- 4032354 TI - Audit of the drug treatment of Parkinson's disease in general practice. AB - In a general practice population of 57 000, 32 patients suffering from Parkinson's disease were identified from repeat prescription indexes and direct questioning of all members of the primary health care team. Of these patients 26 were receiving an L-dopa preparation and 10 an anticholinergic drug. The only newer drug found to be in use was bromocriptine and three patients were receiving this treatment.Of the 26 patients receiving an L-dopa preparation one received L dopa alone, six L-dopa with benserazide (Madopar, Roche) and 19 L-dopa with carbidopa (Sinemet, Merck, Sharp and Dohme). The patients treated with Sinemet were receiving inadequate doses of carbidopa - three quarters received less than 75 mg per day which was in part a reflection of the low doses of L-dopa the patients received, the average dose being 468 mg per day. The L-dopa preparations were given in adequately spaced doses.The general practitioner made the diagnosis in 20 of the 32 cases and was in control of the drug therapy in 15 cases, however 25 cases were referred for specialist advice. PMID- 4032355 TI - Myocardial infarction: hospital and home management in Northern Ireland. AB - Some 262 general practitioners in the Belfast area were asked to complete a questionnaire about their attitudes and practice regarding the management of myocardial infarction at home. Of the 211 responders, only nine per cent would sometimes consider home care for patients under 65 years of age, although 55 per cent would sometimes consider home care for those over 65 years and three per cent preferred home management for this age group. In the year preceding this study, seven per cent of these general practitioners treated only 22 myocardial infarction patients under 65 years of age at home (two per cent of all cases in the area). Home care for myocardial infarction patients appears to be less popular in Belfast than in other parts of the United Kingdom. The views of the general practitioners concerning home care are discussed. PMID- 4032356 TI - Prescribing--a case for prolonged treatment. AB - In an earlier study it was shown that general practitioners changed some of their prescribing habits when they were given detailed analyses of their prescriptions every six months for two years and provided with opportunities to discuss the information with participating colleagues. A follow-up study of the same doctors two years later revealed that most of the effects of the intervention had disappeared, though the increase in generic prescribing persisted. It is concluded that a more sustained intervention is needed to bring about more lasting change. PMID- 4032357 TI - Geriatric screening: a reappraisal of preventive strategies in the care of the elderly. PMID- 4032358 TI - What use is generic prescribing? AB - The dispensing of generic preparations at four dispensing chemist shops was investigated by means of a questionnaire. Certain generic prescriptions result in the dispensing of proprietary products despite the existence of generic preparations, and the pharmacist may be reimbursed for the cost of the proprietary drug which has been dispensed. Not all generic prescriptions result in the dispensing of cheaper drugs because of the methods of payment to chemists. If doctors write more generic prescriptions there will ultimately be more dispensing of generic products. Even in the case of drugs still under patent, prescribing by generic name should be encouraged. The savings achieved by generic prescribing are to some extent at the cost of the dispensing chemists. The method and scale of payments for dispensing requires urgent review. PMID- 4032359 TI - Familial hypercholesterolaemia. PMID- 4032360 TI - The general practitioner and the alcoholic. PMID- 4032361 TI - Continuing medical education. PMID- 4032362 TI - William Pickles lecture 1985. Change and continuity. PMID- 4032363 TI - Care of malignant disease in an urban practice. AB - The prevalence, incidence and care of malignant disease in an urban general practice were studied over a one-year period. Prevalence of malignant disease was 13.1 per 1000 patients, with an incidence of 1.9 per 1000 patients per year. The mortality rate over the year was 2.6 per 1000 patients per year.Patients with malignant disease generated twice as many primary care consultations as the average practice patient and home visiting was increased fourfold. This increased visiting was most apparent for terminal-care patients. Nevertheless, the increase in consultations did not fully reflect the amount of time, energy and emotional support given by the primary care team. PMID- 4032364 TI - Comparison of standards in training and non-training practices. AB - The in-practice component of vocational training should take place in practices working to high clinical and teaching standards. By means of a survey of its members, the Severn Faculty of the Royal College of General Practitioners was able to compare training practices with the criteria of the Joint Committee on Postgraduate Training for General Practice, and with non-training practices. The training practices fell short of the criteria in a few areas, but the differences between the training and non-training practices were extensive. Progress towards achieving the standards set by the criteria should be monitored, and the criteria themselves should be made more precise. PMID- 4032365 TI - Frequent attenders in general practice: medical, psychological and social characteristics. AB - A group of frequent attenders at a general practice surgery have been studied by comparison with a group of age-and sex-matched controls. Frequent attenders are distinguished by a high predisposition to neurotic illness (as measured by the ;N' score of the Eysenck personality questionnaire) and a high prevalence of affective neurosis. Poor past physical health was commonly found among the frequent attenders and comprised for the most part the common chronic physical illnesses. Of the social characteristics studied only marital breakdown was found significantly more often in frequent attenders than controls. PMID- 4032366 TI - Maternity care: a duplication of resources. PMID- 4032367 TI - Characterization of low density lipoprotein receptors in freshly isolated leukemic guinea pig lymphocytes (L2C). AB - The present study shows that L2C leukemic guinea pig lymphocytes have 10 times as many low density lipoprotein (LDL) receptors per cell as normal lymphocytes. The affinity of these receptors is higher for guinea pig LDL than for human LDL. In contrast to normal cells, in which the degradation of the receptor-bound LDL is quite efficient, the leukemic cells only degraded a small fraction of these same receptor-bound LDL. Thus, the internalization index was nearly 4 times higher in the normal cells than in the leukemic cells. In L2C cells, cholesterol homeostasis derived 38% of its cholesterol input from receptor-mediated degradation of LDL and 62% from cholesterol synthesis, whereas in normal cells, these fractions were 97% and 3% respectively. PMID- 4032368 TI - Effect of rapid warming of boar semen on sperm morphology and physiology. AB - The effect of rapid dilution (1:8 with BTS or 1:6.5 with KRP) and temperature change on sperm morphology and physiology were studied using boar spermatozoa pre diluted in BF5 diluent. Rapid dilution of cold semen (5 degrees C) with a warm solution (37 degrees C) caused marked acrosomal changes which were most prominent in the anterior region. The acrosomal damage appeared to be caused mainly by rapid warming. In contrast to rapid cooling, rapid warming had little effect upon motility, glutamic-oxaloacetic transaminase release and respiration. PMID- 4032369 TI - On mammalian sperm dimensions. AB - Data on linear sperm dimensions in mammals are presented. There is information on a total of 284 species, representing 6.2% of all species; 17.2% of all genera and 49.2% of all families have some representation, with quantitative information missing only from the orders Dermoptera, Pholidota, Sirenia and Tubulidentata. In general, sperm size is inverse to body mass (except for the Chiroptera), so that the smallest known spermatozoa are amongst those of artiodactyls and the largest are amongst those of marsupials. Most variations are due to differences in the lengths of midpiece and principal piece, with head lengths relatively uniform throughout the mammals. PMID- 4032370 TI - Photoperiodic control of meiosis in the male Syrian hamster (Mesocricetus auratus). AB - Male Syrian hamsters exposed to short photoperiods of 6 h light/day (6L:18D) show regression of the testes within 12 weeks. Chromosome preparations of the meiotic stages (pachytene, metaphase I (MI) and metaphase II (MII)), testicular weights relative to body weights, sperm counts, seminiferous tubule diameter and histological appearance were examined at intervals during regression and subsequent recovery in a long photoperiod (14L:10D). The fall of testicular weight was associated with the decrease in tubule diameter. Spermatogenesis and sperm count were reduced rapidly and finally ceased after 10 weeks in short days. The numbers of MI and MII cells relative to 100 pachytene cells progressively decreased during the short-day treatment, although the ratio of MI:MII stayed constant whenever there was meiotic activity (except in the first week of the recovery phase). This suggests that an increasing proportion of pachytene cells did not progress to MI with increased time in short days, but cells which did reach MI progressed to MII in the same proportions as in the control testes. Meiosis ceased after 10 weeks in short days. Recovery in the long days was marked by a peak in the number of MI and MII cells/100 pachytene cells soon after the return to long days. This preceded the return (to control values) of the sperm count by 10 weeks. Initial recovery in the first 3 weeks was very rapid in all the determined values. PMID- 4032371 TI - Functional arterio-venous anastomoses between the testicular artery and the pampiniform plexus in the spermatic cord of rams. AB - Blood flow to the testis, haemoglobin oxygen saturation and testosterone concentration in arterial and venous testicular blood vessels were studied in Texel rams in the breeding and non-breeding season. Blood flow in the proximal and distal testicular artery was measured electromagnetically. The mean flow in the proximal testicular artery was 18.5 ml/min and in the distal testicular artery 7.5 ml/min, and there was no detectable seasonal influence. Haemoglobin oxygen saturation and testosterone concentration were measured in the saphenous artery and vein, the distal testicular artery and vein, and in the proximal testicular vein. The haemoglobin oxygen saturation in the proximal testicular vein was significantly higher than in the distal testicular vein in both seasons. The mean testosterone concentration was significantly lower in the proximal testicular vein than in the distal testicular vein in both seasons. Based on haemoglobin oxygen saturation and testosterone data, it was calculated that between 28 and 46% of the testicular arterial blood was bypassing the testis and was directly flowing through arterio-venous anastomoses towards the pampiniform plexus in the spermatic cord of conscious rams. In anaesthetized rams 55 and 64% of the blood was flowing directly from the testicular artery to the pampiniform plexus based on blood flow data. Transfer of testosterone and oxygen by passive diffusion from the testicular artery to the pampiniform plexus and vice versa in the spermatic cord was not detected. PMID- 4032372 TI - Photoperiodic time measurement is maintained in undernourished lambs with delayed puberty. AB - Beginning at 42 weeks of age undernourished females that had been maintained outdoors were exposed to long days (15L:9D) or short days (9L:15D). After 6 weeks, both groups were placed on short days, and ad-libitum feeding was begun. Rapid 'catch-up' growth occurred similarly in both groups. However, the response to oestradiol negative feedback regulation of LH secretion differed greatly. Short-day lambs remained hyperresponsive to oestradiol inhibition, and circulating LH remained low, a condition that typifies immaturity of the system governing LH secretion. In the females exposed to the long-day-short-day sequence, circulating LH began to increase 10 weeks after the end of long days; this change is characteristic of the neuroendocrine alteration that occurs during puberty. These findings indicate that the growth-retarded lamb can differentiate long days from short days, and can therefore continue to accumulate photoperiod information during prolonged periods of undernutrition. PMID- 4032373 TI - Metabolic clearance and production rates of oestradiol and progesterone during pubertal and postpubertal development in gilts. AB - The crossbred gilts studied were aged 80 days (prepubertal), 180 days (prepubertal or postpubertal) and 260 days (postpubertal or pregnant). Estimates of metabolic clearance rate (MCR) of oestradiol and progesterone were consistently less (21 and 27%) in plasma than in blood, and these differences were not influenced by age of gilt. The MCR (1/day per kg body weight) for oestradiol and progesterone in plasma was greater (P less than 0.05) for 80-day old prepubertal gilts than for older gilts. The MCR values of oestradiol and progesterone were similar in 180-day-old and 260-day-old gilts independent of reproductive state. Production rate (PR) of oestradiol and progesterone increased with age (80-180 days), and age and reproductive state differences were much more pronounced for PR of progesterone than of oestradiol. These results support the hypothesis that a reduction in the MCR and an increase in PR of oestradiol and progesterone in the gilt are associated with the process of pubertal development, and changes in gonadal steroid concentrations appear not to alter the MCR of oestradiol and progesterone. PMID- 4032374 TI - Ultrastructural localization of calcium ions in ram spermatozoa before and after cold shock as demonstrated by a pyroantimonate technique. AB - Ram spermatozoa were subjected to cold shock before fixation in pyroantimonate osmium. Ultrathin sections revealed an electron-dense particulate precipitate in association with the cells. The precipitate was shown to be related to the presence of calcium by exposure of the material to EGTA which reduced or completely eliminated the deposits. In the acrosome region, very little precipitate was evident when the plasma membrane was intact. Cold shock resulted in the disruption of the plasma membrane. When the acrosome remained intact, precipitate was concentrated just anterior to the equatorial segment, but many cells also had acrosomal disruption and then a more even distribution of precipitate was seen on the outer acrosomal membrane. Precipitate was rarely visible within or beneath the acrosome. Post-acrosomally, calcium pyroantimonate deposits were frequently present in the dense lamina beneath the plasma membrane and these became more intense after cold shock. Midpiece sections revealed a few large granules beneath the plasma membrane and a fine particulate precipitate within mitochondria. Similarly, the fine precipitate was also associated with the outer dense fibres in midpieces and tails. Cold shock did not apparently increase the extent or intensity of precipitates in these sites. PMID- 4032375 TI - Sodium, potassium, calcium, magnesium, zinc, citrate and chloride content of human prostatic and seminal fluid. AB - The ionic composition of human prostatic fluid varied greatly between individuals, reflecting the secretory activity of the gland and the presence or absence of prostatic inflammatory disease. In normal prostatic fluid the major anion was citrate, while chloride concentrations were lower. Their counterions were mainly sodium and potassium, together with calcium, magnesium and zinc. Prostatic secretions from men with prostatitis comprised mainly sodium and chloride. The electrolytes were closely correlated to each other (except for sodium, which was essentially invariant at about 145 nm). The molar changes per mole of citrate were about 0.52, potassium; -0.53, chloride; 0.17, calcium; 0.14, magnesium; and 0.09, zinc. The pH was also associated with citrate, decreasing from 8.0 to 6.2 as the citrate increased. These various ionic changes can be explained as responses to citrate secretion, without the need to propose specific transport mechanisms for the other ions measured. The marked effect of prostatic inflammation on the composition of prostatic fluid can be seen as being due mainly to decreased secretion rather than active modification. PMID- 4032376 TI - Disruption of pair bonding induces pregnancy failure in newly mated mongolian gerbils (Meriones unguiculatus). AB - The efficacy of several exteroceptive factors including exposure to a 'strange' male, were tested to induce pregnancy failure in newly mated Mongolian gerbils. Only physical separation of monogamous pairs consistently induced pregnancy failure. This phenomenon was restricted to the immediate period after mating and is believed to be due to disruption of pair bonding, with associated luteal and implantation failure. Concurrent lactation annulled this effect. PMID- 4032377 TI - Steroid metabolism by endometrial and conceptus tissues during early pregnancy and pseudopregnancy in gilts. AB - Endometrial and conceptus tissues were obtained on Days 10.5, 11, 12, 16 and 25 of pregnancy and Day 25 of pseudopregnancy of gilts and incubated for 6 h in Minimal Essential Medium (5 ml) containing 35 ng [3H]progesterone. Metabolism of [3H]progesterone to oestrone, oestradiol and oestriol was determined by gas and high-pressure liquid chromatography and successive recrystallizations with unlabelled standards. Conceptuses collected between Days 10.5 and 12 were spherical, tubular or filamentous and incubated with 500 mg endometrium and [3H]progesterone. Production of oestrone by spherical conceptuses was not detected, but was 44-47 pg/tubular conceptus and 21 pg/filamentous conceptus. A similar trend was observed for oestradiol. Conceptus tissues from Days 16 and 25 (chorion) were most active in producing oestrone (123 and 520 pg/mg tissue, respectively) and oestradiol (277 and 876 pg/mg tissue, respectively). Endometrial oestrogen production was less than that for conceptus tissue for oestrone and oestradiol on Days 16 and 25 of gestation. Coincubations of endometrium and conceptus tissues had lower oestrogen production than conceptus alone. Endometrium from Day 25 of pseudopregnancy metabolized [3H]progesterone to several non-polar metabolites, but no oestrogens were detected. An unidentified phenolic metabolite of [3H]progesterone was detected in higher quantities than either oestrone or oestradiol; 445 to 461 pg/conceptus at the tubular stage. These results indicate temporal changes in the conversion of [3H]progesterone to oestrogens by conceptus and endometrial tissue from pregnant gilts, but not endometrium from pseudopregnant gilts. PMID- 4032378 TI - Relationship between corpora lutea or fetal number and plasma concentrations of progesterone and testosterone in mice. AB - Blastocysts (1-14) were transferred unilaterally into 63 pseudopregnant mice which were killed on Day 17. Plasma progesterone concentrations were significantly (P less than 0.05) lower in animals with one fetus than in those with 2-5 or 9-14 fetuses. Plasma testosterone concentrations were correlated with fetal number in mice with 1-13 fetuses (P less than 0.001). The total placental content of chorionic gonadotrophin in 13 litters varied directly with the number in the litter (1-6), and was 1.67 +/- 0.15 ng/placenta. The number of corpora lutea per mouse was negatively correlated with mean CL volume per mouse (P less than 0.001), and the number of conceptuses was positively correlated with mean CL volume per mouse (P less than 0.001). The effect of conceptuses on the ovary was systemic. The relationship between plasma testosterone concentration and conceptus number may be due to gonadotrophins acting on the ovary, or androgens produced by the placenta or fetus. PMID- 4032379 TI - Corpora lutea with a short life-span induced by rams in seasonally anovulatory ewes are prevented by progesterone delaying the preovulatory surge of LH. AB - Seasonally anovulatory Merino ewes isolated from rams were allocated to three treatments before the re-introduction of rams. Ten ewes received a single injection of progesterone (20 mg), 18 ewes received the injection of progesterone but had the ram-induced preovulatory surge of LH replaced by a series of injections of GnRH 24 h after the introduction of the rams, and 20 control ewes had no hormone treatment. Of the 48 ewes, 44 ovulated within 5 days of the introduction of rams and the treatments had no significant effect on the incidence of ovulation. The frequency of corpora lutea with a short life span (the interval between successive preovulatory surges of LH being 5.1 +/- 0.9 days) was 72% for control ewes and 58% for ewes treated with progesterone and GnRH, but such CL were prevented completely after the injection of progesterone alone (P less than 0.001). The injection of progesterone also delayed the preovulatory surge of LH (P less than 0.001). These results suggest that progesterone assures normality of corpora lutea by lengthening the period of gonadotrophin priming of follicles before ovulation. PMID- 4032380 TI - Ability of mouse embryos to degranulate mast cells in vitro. AB - Mouse embryos flushed from the reproductive tract on Day 4 or 5 post coitum degranulated peritoneal mast cells in vitro. The degranulating activity of embryos developed with age of embryos: it was absent with Day-3 embryos, present with Day-4 embryos and was increased with Day-5 embryos. Day-4 embryos cultured for 24 h also exhibited degranulating activity. Such activity was even greater for embryos cultured for 48 h. As the degranulating activity of the incubated embryos increased, it was accompanied by an increase in the degranulating activity of the culture medium. PMID- 4032381 TI - Anti-trophoblast antibody responses during normal human pregnancy. AB - During the course of a normal uncomplicated human pregnancy the mother generates an antibody response directed against determinants present on the plasma membrane of the outer fetal layer of the term placenta, the syncytiotrophoblast. The response, measured by an ELISA that utilises syncytiotrophoblast plasma membrane as the antigenic target, is predominantly IgG in nature, but with a minor contribution from IgM molecules. Maximum responses were observed during the first trimester and the levels gradually declined as the pregnancy progressed. On a population basis, this antibody response profile was mainly restricted to first and second pregnancies, although anti-trophoblast antibody responses could be detected in multiparous women but with a greatly reduced incidence compared with primipara. Mechanisms to account for these observations are discussed. Throughout, the anti-trophoblast antibody levels detected in pregnancy sera were compared with the background levels which were observed in sera obtained from males and nulliparous non-pregnant females. PMID- 4032382 TI - Maturation and function of the hamster spermatozoon probed with monoclonal antibodies. AB - To investigate the surface of the mammalian spermatozoon during its maturation in the epididymis, seven monoclonal antibodies were raised in mice against intact spermatozoa (and isolated sperm heads) recovered from the cauda epididymis of the golden hamster. These antibodies, which with one exception were species specific, recognized various membrane components over restricted regions of the sperm head and tail. During epididymal transit the localisation of four antigens bound by these antibodies was considerably altered. In two cases, antigens were first detected on spermatozoa in the distal corpus epididymis where sperm fertilising capacity is initially acquired. A monoclonal antibody which bound to the acrosome and midpiece specifically blocked fertilisation of intact oocytes of the hamster in vitro. Preliminary characterisation of the antigens was undertaken. PMID- 4032383 TI - Detection of macrophages and the characterization of Fc receptor-bearing cells in the mouse decidua, placenta and yolk sac using the macrophage-specific monoclonal antibody F4/80. AB - A mouse macrophage-specific rat monoclonal antibody, F4/80, has been used to detect directly macrophages in short term cultures of mouse decidua, fetal placenta and yolk sac and to investigate the identity of Fc receptor (FcR) bearing cells in these tissues. We find that a significant proportion of FcR positive cells in decidual, placental and yolk sac tissues are macrophages as defined by the expression of the macrophage marker, F4/80 antigen. Macrophages may act as immunocompetent cells near to the maternal-fetal interface and play a significant role in the mechanism of the transfer of passive immunity from mother to fetus across the mouse yolk sac. PMID- 4032384 TI - The effect of estradiol on human myelomonocytic cells. 1. Enhancement of colony formation. AB - Cyclic changes were observed in the content of blood monocytes during the menstrual cycle of normal women. Elevated blood monocytes were found during the ovulation period as well as in other conditions which are associated with increased blood estradiol (E2). To understand the possible association between E2 and monocytosis, we analysed the in vitro effect of E2 on the development of myelomonocytic colonies in culture. E2 in physiological concentrations was found to increase the number of colonies developed from peripheral blood mononuclear cells (PBM) of both females and males. The optimal concentration for the augmenting effect on males' PBM was lower than that for females. Mononuclear cells derived from cord blood, which yielded much higher numbers of colonies than adult PBM, also responded to the stimulatory effect of E2. Estrone and estriol were less effective than E2 in adult PBM. In contrast, progesterone, diethylstilbestrol and testosterone did not affect the number of colonies at the range of physiological concentrations tested. The anti-estrogen Tamoxifen did not inhibit the stimulatory effect of E2. The augmenting effect of E2 on monomyelocytic colony formation may explain at least in part the increase in blood monocyte content of women with high E2 as well as other phenomena of macrophage and granulocyte changes associated with the menstrual cycle. PMID- 4032385 TI - Maternal--fetal immune interactions and the maintenance of major histocompatibility complex polymorphism in the rat. AB - In several different strain combinations of rats, an R2 backcross was used to assess the relative fitness of progeny MHC-incompatible with their mothers as compared to that of MHC-compatible progeny. None of the various treatments used to alter maternal immunoregulatory processes, namely splenectomy, active or adoptive immunization, or the induction of transplantation tolerance, was able to perturb consistently the population distribution of RT1 antigens. Though the extreme variability of RT1 heterozygote excess remains poorly understood, studies of parity-associated changes in the population distribution of RT1 heterozygotes: RT1 homozygotes nonetheless do support the hypothesis that the spleen is important to the immunoregulatory control of these phenomena. PMID- 4032386 TI - Antepartum heart rate testing in diabetic pregnancy. AB - Fetal death in utero remains a significant contributor to diabetics' perinatal mortality despite the reassuring results of antepartum heart rate testing. We retrospectively reviewed 48 pregnancies (one set of twins) of class B-F diabetic women with a reactive nonstress test (NST) or a negative contraction stress test (CST) within one week of delivery. Four fetal deaths occurred four to seven days after the test; no fetal deaths occurred within three days of it. We advocate initial screening with the NST, followed by a CST if the NST is nonreactive. Testing should be done more often than weekly. PMID- 4032387 TI - Observations on perinatal heart rate monitoring. II. Quantitative unreliability of Doppler fetal heart rate variability. AB - Fifty-three fetal heart rate (FHR) tracings obtained by direct ECG monitoring during labor and 24 simultaneous external Doppler FHR tracings were analyzed for the quantitative assessment of baseline FHR variability. The beat-to-beat difference in FHR subsumed by 90% of all beat-to-beat changes within a tracing was taken as the index of variability of that tracing. This index correlated well with the visual assessment of variability for both internal ECG records (Spearman rank correlation coefficient, rs, = 0.71) and external Doppler records (rs = 0.78). However, there was no correlation between the variability index of the Doppler FHR records and that of simultaneous ECG FHR records (r = 0.11, p greater than 0.6). This finding casts doubt on the use of the presence of "normal" FHR variability as a sign of fetal well-being during antepartum FHR monitoring with current Doppler equipment. PMID- 4032388 TI - Maternal-infant separation and breast-feeding. The return to work or school. AB - Breast feeding is now practiced by more than 50% of new mothers, many of whom return to work or school within six to eight weeks postpartum. Their breast feeding experience need not, and should not, be terminated because of this temporary, though regular, separation from their infants. The obstetrician has a role in facilitating continued breast-feeding after the return to work or school. Counseling these patients should include a discussion of hand expression and breast pumping, the means of storing human milk, infant changes related to regular maternal absences and avoiding exhaustion. PMID- 4032389 TI - Effect of intrauterine antibiotic lavage after cesarean birth on postoperative morbidity. AB - Intrauterine lavage using broad-spectrum antibiotics after cesarean section has been reported to reduce maternal morbidity, but many such patients are not at high risk for postoperative infection. This study tested intrauterine antibiotic lavage in patients at risk for infectious morbidity. The patients were randomly assigned to one of three groups based on the last digit of the hospital admission number. Group I received no lavage, group II received lavage with 800 ml of saline plus 2 gm of cefamandole nafate in the intrauterine incision, bladder flap and peritoneal cavity, and group III received a similar lavage using 800 ml of saline alone. There was a significant decrease in maternal hyperpyrexia (simple morbidity) as well as serious infection in both lavage groups as compared to the control group (p less than 0.01 and 0.05, respectively). Also, there was significantly reduced morbidity when the antibiotic lavage was compared to the saline technique (p less than 0.001). The use of intrauterine lavage with saline, with or without antibiotics, appears helpful in reducing postoperative morbidity in patients at high risk for infectious morbidity after cesarean section. PMID- 4032390 TI - Acupuncture for the induction of cervical dilatation in preparation for first trimester abortion and its influence on HCG. AB - Cervical dilatation in preparation for first-trimester abortion using acupuncture at loci SP6 and LI4 was studied in 20 patients, who were compared to a control group in whom no preparation was used. Ninety percent of the patients had successful acupuncture procedures. As judged by Hegar dilators, the increase in cervical dilatation in those 18 patients was significantly greater than in the controls. No significant side effects were observed. The effect of acupuncture on serum human chorionic gonadotropin (HCG) as a pregnancy marker was evaluated in 12 patients. No statistically significant difference in the change in HCG was noted in terms of the controls, indicating an absence of abortifacient activity with acupuncture. PMID- 4032391 TI - Artifacts seen commonly on ultrasonography of the fetal cranium. AB - Common artifacts seen during ultrasound examination of the fetal cranium and that may simulate pathology include hypoechoic parenchyma, noise in the near field, focal sonolucent areas, reverberation echoes and shadowing from portions of the skull base. Specific techniques can help one recognize, decrease or eliminate them. PMID- 4032392 TI - A vaginal delivery protocol for the term breech infant utilizing ball pelvimetry. AB - Ball pelvimetry has been utilized at the Medical Center Hospital of Vermont to evaluate infants with breech presentation for vaginal delivery. That technique provided measurements of both the fetal head volume and maternal pelvic capacity so that relative fetomaternal relationships could be established. Between January 1979 and December 1981, 107 patients in spontaneous labor with term pregnancy were evaluated with the protocol. Inadequate pelvimetry and hyperextension of the fetal head occurred in 21 patients (20%). Of the 86 patients who were allowed to labor, 51 (59%) had a vaginal delivery. The total cesarean section rate was 52%. Vaginal delivery in our highly selected patient population did not increase neonatal morbidity. There were no neonatal deaths. PMID- 4032393 TI - Chlamydial colonization of the cervix in pregnant adolescents. AB - We studied the incidence of Chlamydia trachomatis colonization of the cervix in pregnant adolescents and analyzed the effect of such colonization on pre-, intra and postpartum events. A significant increase in post-vaginal-delivery endometritis as well as an increase in other sexually transmitted diseases occurred in patients colonized by C. trachomatis. PMID- 4032394 TI - Interstitial pregnancy. A case report. AB - Interstitial pregnancy is uncommon, and the correct diagnosis requires awareness of this form of ectopic pregnancy. PMID- 4032395 TI - Puerperal inversion of a bicornuate, unicollis uterus. A case report. AB - The diagnosis and management of uterine inversion at term were complicated by an uninverted horn at the level of the contraction ring. PMID- 4032396 TI - Stenosis and fistulae with neglected vaginal foreign bodies. A case report. AB - Foreign bodies present in the vagina for long periods of time are infrequent but potentially serious findings in adult women. Significant injury can occur to bowel, bladder or other pelvic structures. Repair of fistulae is delayed following removal of the foreign bodies until the chronic inflammation produced by the objects has resolved. Coexisting psychiatric illness or physical abuse may complicate the evaluation and treatment of some women with long-standing vaginal foreign bodies. PMID- 4032398 TI - Combined intrauterine and ovarian pregnancy. A case report. AB - A case of combined ovarian and intrauterine pregnancy occurred. The ovarian pregnancy was an incidental finding during cesarean section. A literature survey revealed only 17 cases of combined ovarian and intrauterine gestation. PMID- 4032397 TI - Atrial myxoma as a complication of tocolytic therapy. A case report. AB - A 27-year-old woman who presented with premature labor was given ritodrine for tocolysis. During the administration of the beta-sympathomimetics she developed cardiac changes, including subendocardial ischemia on EKG and an intermittent early diastolic sound. Echocardiography revealed a large left atrial myxoma. It was removed during pregnancy, and the patient tolerated the procedure well. The mechanism of the ischemia was believed to result from the space-occupying mass of the myxoma, preventing adequate atrial filling and subsequent congestive failure. It is recommended that patients who develop cardiac symptoms during tocolysis with beta-sympathomimetics undergo further investigation to rule out under-lying pathology. PMID- 4032399 TI - Issues in the evaluation of rheumatology education in medical schools. PMID- 4032400 TI - Phospholipase A2 activity in sera and synovial fluids in rheumatoid arthritis and osteoarthritis. Its possible role as a proinflammatory enzyme. AB - Phospholipase A2 (PLA2) activity was found in the sera and synovial fluids (SF) in rheumatoid arthritis (RA) and osteoarthritis (OA). PLA2 activity in RA SF was 6158 +/- 549 (SEM) U/ml (n = 48) and in RA sera 554 +/- 175 U/ml (normal sera-115 +/- 12 U/ml). In OA SF PLA2 activity was 5069 +/- 542 U/ml (n = 28), and in OA sera 268 +/- 55 U/ml. There was no significant difference between SF PLA2 activity in RA and OA. PLA2 activity in SF did not correlate with muramidase (lysozyme), beta-glucuronidase, total protein or white cell count, which were all significantly higher in RA SF than OA. A positive correlation between PLA2 in SF and matched sera was found in both RA and OA. It may be concluded that significant elevation of extracellular PLA2 occurs in both RA and OA, especially in the SF. The fact that high PLA2 did not correlate with other enzymes such as lysozyme and beta-glucuronidase, which are usually high in RA and low in OA SF, may mean that the handling of PLA2 in the joint space is different from other enzymes. PMID- 4032401 TI - Remission in rheumatoid arthritis. AB - Four hundred and fifty-eight patients whose clinical data had been prospectively entered into a rheumatic disease databank were studied for remission utilizing remission criteria of the American Rheumatism Association and criteria modified for chart review. During the period of observation 86 of 458 or 18.8% had at least one remission by investigators' assessment on chart review and 18.1% by application of ARA criteria. Patients were followed for 1131 patient years and remission occupied 97 patient years. For patients achieving remission this period represented 34.5% of their followup duration. The median length of remission was 10 months. Nineteen (18.6) percent of gold treatment courses and 16.7% of penicillamine courses resulted in remission. Fourteen (13.6) percent of patients who never received remittive therapy also had remissions. The ARA Preliminary Criteria for Clinical Remission in Rheumatoid Arthritis displayed a sensitivity of 80.2% and a specificity of 96.2% in this population. In patients receiving remittive therapy, female sex, disease onset before age 60, and early development of erosions were associated with decreased proportion of remission. PMID- 4032402 TI - Relationship between nailfold capillary microscopy and salivary capillary basement membrane width in Raynaud's disease and progressive systemic sclerosis. AB - To assess the relationship between a nailfold scleroderma pattern and histopathological data, we compared the results of nailfold capillaroscopy with capillary basement membrane width of labial salivary glands in 25 patients with either a Raynaud's disease (RD: 12 patients) or a progressive systemic sclerosis (PSS: 13 patients). The sensitivity of a capillaroscopic scleroderma pattern for capillary basement membrane thickness is of 75%. These results confirm the usefulness of in vivo capillary examination for the early diagnosis of PSS. PMID- 4032403 TI - Abnormal bowel permeability in ankylosing spondylitis and rheumatoid arthritis. AB - Intestinal permeability was measured using a low molecular weight polyethylene glycol as a permeability marker in patients with osteoarthritis, ankylosing spondylitis (AS) and rheumatoid arthritis (RA). Patients with AS showed a significant increase in bowel permeability when compared to controls. Intestinal permeability was also increased in patients with active RA but was less than the control group in RA patients who did not have active joint disease. PMID- 4032404 TI - The epidemiology of joint complaints in patients with psoriasis. AB - Joint complaints of 1285 patients treated for cutaneous psoriasis were analyzed to better define the epidemiology of arthritis among psoriasis patients selected on the basis of cutaneous rather than rheumatologic disease. Nearly 40% of patients suffered from arthralgia, and 20% had been diagnosed as having psoriatic arthritis (PA). Patients with PA had more extensive cutaneous disease and more frequently had a family history of PA. PA patients frequently noted an association between the activity of their arthritis and the activity of their cutaneous disease. Antinuclear antibodies, uric acid, and white blood cell count had little predictive value in PA. PMID- 4032406 TI - An evaluation of rheumatology education at Canadian medical schools. AB - The present study uses data from a nationally administered multiple choice examination (MCE) to assess the performance of Canadian medical students in rheumatology. An average of 1722 medical students undertook to write the Medical Council of Canada (MCC) examination each year between 1978-82. Between 17 and 29 of the 516 MCE questions were of a rheumatological nature and the success rate of students from the 16 Canadian medical schools varied between 65.5 and 78.5% in any given year. No direct correlation was noted between the students' MCE performance and the amount of rheumatology education given at an individual university. Analysis of Arthritis Society Undergraduate Statistics indicated that the average medical student in Canada receives 17.5 h of didactic lectures, 10.4 h of clinical bedside demonstration and 8.9 h of direct supervision of rheumatologic patients by rheumatologists. PMID- 4032405 TI - Aspirin dosing using 15 grain enteric coated tablets. AB - A high unit dose (15 grain/975 mg) enteric coated aspirin preparation was studied in normal individuals and patients with arthritis to determine how readily well tolerated, therapeutic (150-300 micrograms/ml) salicylate (SA) levels could be achieved using a twice daily dosing regimen. Of 36 participants enrolled, 33 (92%) achieved this goal (mean SA = 224 micrograms/ml), while in the remaining 3 an initially toxic level fell below the therapeutic range after reducing the dose by one tablet/day. Although the relationship between dose (mg/kg) and steady state SA levels was roughly linear (r = 0.74), in some subjects there was a striking incremental change in the SA level when the dose was adjusted. Over 90% of subjects taking a starting dose between 45-60 mg/kg/day achieved a therapeutic level. Thus, antiinflammatory therapy using 15 grain/975 mg enteric coated aspirin given twice daily appears to be feasible. PMID- 4032407 TI - Methotrexate induced false photosensitivity reaction. AB - Methotrexate is now being used in the treatment of a variety of intractable rheumatologic conditions. We report a patient with polymyositis who developed mild erythroderma after sun exposure. Forty-eight h later he received his weekly dose of methotrexate. Within 24 h the resolving rash erupted into an intense dusky red dermatitis with eventual formation of confluent bullae. The patient had a methotrexate induced ultraviolet reactivation reaction also known as a "false photosensitivity" reaction. This reaction has been reported in dermatologic publications but not in the rheumatologic literature. PMID- 4032408 TI - Paracoccidioides brasiliensis arthritis. Report of a case and review of the literature. AB - A case of Paracoccidioides brasiliensis arthritis is presented. Emphasis on early diagnosis and treatment is made. Natives of endemic areas for paracoccidioides could present elsewhere with dissemination of this disease. PMID- 4032409 TI - Bursal fat necrosis as the presenting manifestation of pancreatic disease: light and electron microscopic studies. AB - Bursal swelling with inflammatory lipid laden creamy appearing bursal fluid is described in an alcoholic patient with pancreatitis. Joints swollen at the same time had clearer effusions. Morphologic and biochemical studies support the necrotic bursal membrane as the source for the synovial fluid lipids. PMID- 4032410 TI - Pulmonary hypertension in systemic lupus erythematosus. AB - The occurrence of pulmonary hypertension in systemic lupus erythematosus (SLE) has been rarely reported. To date only 18 well documented cases of SLE with pulmonary hypertension have been published. We review the literature on pulmonary hypertension in SLE, and add the case of a young woman with a recent onset of both SLE and pulmonary hypertension. Hemodynamic studies were carried out before and during treatment with nifedipine and hydralazine alone and in combination. Despite improvement in pulmonary vascular resistance, pulmonary pressures were unaffected by the drugs, although our patient had symptomatic relief. PMID- 4032411 TI - Chronic active hepatitis associated with polymyositis. Association with precipitating mitochondrial M-B antibody. AB - A 20-year-old black female presented with chronic active hepatitis and polymyositis. Interstitial lung disease and transient polyarticular arthritis were also observed, but other features of systemic lupus erythematosus, scleroderma and Sjogren's syndrome were absent. Both myositis and hepatitis responded to prednisone and azathioprine. The patient's serum contained an unusual autoantibody reacting with mitochondrial proteins (M-B) in immunodiffusion. PMID- 4032412 TI - Rapid development of gouty tophi after diuretic therapy. AB - Increasing attention has been drawn to the role played by diuretics in the pathogenesis of gout, particularly in the elderly. We describe an elderly woman presenting acutely with tophus formation mimicking infection, in whom diuretic therapy was responsible for her disease. Her presentation with acutely inflamed tophi without any history of joint involvement, only 3 months after starting treatment, was highly unusual. PMID- 4032414 TI - Oral chrysotherapy in a hemodialyzed rheumatoid patient. PMID- 4032413 TI - Hemorrhagic cystitis and sicca syndrome secondary to amyloidosis in rheumatoid arthritis. AB - Vesical bleeding and sicca complex proved to be due to unrecognized amyloidosis in a patient with chronic rheumatoid arthritis. The features of amyloidosis of the lower genitourinary tract are outlined. PMID- 4032416 TI - The importance of the lymphatic system. PMID- 4032415 TI - A once-daily antiinflammatory drug, oxaprozin, in the treatment of juvenile rheumatoid arthritis. The Pediatric Rheumatology Collaborative Study Group. PMID- 4032417 TI - Gold induced severe aplastic anemia: medullary autologous reconstitution after immunosuppression. PMID- 4032418 TI - Enteric coated aspirin circumventing gastric retention. PMID- 4032419 TI - Hydroxychloroquine provocation of psoriasis. PMID- 4032420 TI - Septic trochanteric bursitis caused by Fusobacterium gonidiaformans. PMID- 4032422 TI - Analogues of platelet activating factor (PAF). 2. Some modifications of the glycerine backbone. AB - Racemic analogues of platelet activating factor (PAF) that contain a methylene group between the C2 and C3 carbon atoms (39) or between the C1 and C2 carbon atoms (40) have been synthesized. These compounds show reduced platelet aggregation and hypotensive activity as measured against racemic C16 PAF. Compounds in which the C1 carbon atom of PAF is substituted with one or two methyl groups (41 and 42, respectively) or the C3 carbon is substituted with a single methyl group (43) have been synthesized. Platelet aggregation and hypotensive responses produced by these compounds are significantly less than those obtained with racemic C16 PAF. None of the above compounds exhibit a separation of the platelet aggregation and hypotensive activities. PMID- 4032421 TI - 5,6-Diaryl-2,3-dihydroimidazo[2,1-b]thiazoles: a new class of immunoregulatory antiinflammatory agents. AB - A series of substituted 5,6-diaryl-2,3-dihydroimidazo[2,1-b]thiazoles were synthesized and evaluated in the rat adjuvant-induced arthritis and mouse oxazolone-induced contact sensitivity assays to determine the potential of these compounds for use as immunoregulatory antiinflammatory agents. This class of compounds was derived by combining salient structural features of the antiinflammatory agent flumizole and the immunoregulatory drug levamisole. Unlike the latter two, a number of compounds in the target series were found to possess the desired combination of activities. Exploration of structure-activity relationships in the adjuvant-induced arthritic rat assay revealed that optimal potency was exhibited by symmetrically substituted 5,6-diaryl compounds having one of the following alkyl heteroatom or halogen functions at the para position: methoxy, ethoxy, methylthio, N-ethyl-N-methylamino, fluoro, or chloro. Scrambling of these two substituent classes to yield the asymmetrically substituted 5,6 diaryl compounds resulted in potent activity only with the 5-alkyl heteroatom, 6 halo-substituted regioisomers. However in the oxazolone-induced contact sensitivity assay, no consistent relationship of variation in activity with structural change was apparent. The initial target compound 5,6-bis(4 methoxyphenyl)-2,3-dihydroimidazo[2,1-b]thiazole (1) was compared with its progenitors in additional models of inflammation and immunoregulation. PMID- 4032423 TI - Synthesis and biological effects of novel thiocolchicines. 3. Evaluation of N acyldeacetylthiocolchicines, N-(alkoxycarbonyl) deacetylthiocolchicines, and O ethyldemethylthiocolchicines. New synthesis of thiodemecolcine and antileukemic effects of 2-demethyl- and 3-demethylthiocolchicine. AB - Novel and known analogues of thiocolchicine were evaluated in vitro in a tubulin binding assay and in vivo in mice for acute toxicity and in the P388 lymphocytic leukemia assay. This evaluation included N-acyldeacetylthiocolchicines, N (alkoxycarbonyl)deacetylthiocolchicines, thiodemecolcine and its methyl carbamate, and O-ethyl ethers of demethylthiocolchicines. Selective ether cleavage of thiodemecolcine with concentrated sulfuric acid at 50 degree C afforded the 2-demethyl congener, characterized as its N,O-diacetyl derivative. Several of the compounds showed high potency in the tubulin binding assay, matching the potency of colchicine. Several N-(alkoxycarbonyl)deacetylcolchicines (carbamates) exhibited strong binding affinity to tubulin but had only weak activities against the P388 tumor system, suggesting that other factors besides tubulin binding may be important for the biological effects. The compounds potent in the tubulin binding assay and in the P388 leukemia assay in mice were generally also toxic to mice in the acute toxicity test, showing thus a similar behavior of thiocolchicines to that observed earlier with colchicines. A considerable amount of data collected for 2-demethyl- and 3 demethylthiocolchicine suggests that the latter represents a broad-spectrum antitumor agent of considerable promise and possibly a less toxic substitute for colchicine. PMID- 4032424 TI - N-(Aminoalkyl)imide antineoplastic agents. Synthesis and biological activity. AB - The similarity of the side-chain characteristics of 1,4-dihydroxy-5,8-bis[[2-[(2 hydroxyethyl)amino]ethyl]amino]- anthraquinone (DHAQ), discovered by us in 1978, and those of the N-substituted imides of 3-nitro-1,8-naphthalic acid, discovered by other investigators recently, led us to conduct a systematic study on the N (aminoalkyl)-substituted derivatives of a variety of imides. Areas of study included (a) selection of the ring system, (b) modification of the side chain, (c) substitution on certain chosen ring systems, and (d) combinations of the aforementioned variants. Preliminary biological activity screening indicated that N-(dialkylaminoethyl)imides of the 3,6-dinitro- and 3,6-diamino-1,8-naphthalic acid system possessed prominent antileukemia and antimelanoma activity in both in vitro and in vivo experimental tumor systems. PMID- 4032425 TI - Synthesis and antimetastatic properties of stereoisomeric tricyclic bis(dioxopiperazines) in the Lewis lung carcinoma model. AB - Synthesis of trans- and cis-tetrahydrodipyrazino[1,2-a:1',2'-d] pyrazine 1,3,7,9(2H,4H,8H,10H)-tetrone analogues 10 and 11 belonging to the bis(dioxopiperazine) class of antitumor agents and their bis(morpholinomethyl) derivatives 12 and 13 are described with use of 2,5-dimethylpyrazine as the starting material. Synthetic studies utilizing 3,6-disubstituted 2,5 dioxopiperazine precursors are included. Evaluation of 10-13 in the Lewis Lung carcinoma model indicated the bis(morpholinomethyl) analogue cis-13 to be antimetastatic, whereas the trans isomer 12 was toxic at a similar dose effecting a decrease in the life span of treated mice. The parent bis(dioxopiperazines) 10 and 11 were ineffective as antitumor or antimetastatic drugs. PMID- 4032426 TI - Antiparasitic agents. 6. Synthesis and anthelmintic activities of novel isothiocyanatophenyl-1,2,4-oxadiazoles. AB - The syntheses and anthelmintic activities of 31 3- and 5-(isothiocyanatophenyl) 1,2,4-oxadiazoles are reported. In the primary anthelmintic screen, 3-(4 isothiocyanatophenyl)-1,2,4-oxadiazole (39) showed 100% nematocidal activity and 3-(2-furanyl)-5-(4-isothiocyanatophenyl)-1,2,4-oxadiazole (63), 3-(2-furanyl)-5 (2-chloro-4-isothiocyanatophenyl)-1,2,4-oxadiazole (64), and 3-(2-furanyl)-5-(4 chloro-3-isothiocyanatophenyl)-1,2,4-oxadiazole (66) showed 100% taeniacidal activity when administered orally to mice. The two most active members of this series, 39 and 63, were active against the gastrointestinal nematodes of sheep at 100 mg/kg. In addition, 39 was also found to be active against hookworms in dogs at a single, oral dose of 200 mg/kg. PMID- 4032427 TI - Structure-activity relationships of some pyridine, piperidine, and pyrrolidine analogues for enhancing and inhibiting the binding of (+/-)-[3H]nicotine to the rat brain P2 preparation. AB - Previous studies have shown that (+/-)-[3H]nicotine binds to multiple sites in the rat brain P2 preparation. Using a series of pyridine, piperidine and pyrrolidine analogues, the present studies identified drugs with specificity for a separate up-regulatory site that increases the density of nicotine binding at another site. Of these compounds, (+/-)-2-methylpiperidine was the most specific. Some compounds inhibited without enhancing (+/-)-[3H]nicotine binding, but none bound with the very high affinity exhibited by nicotine and none could be classified as specific in inhibiting binding at a specific site. Structural changes in the 1- and 2-positions of pyridine and piperidine appear to be important for conferring specificity for the up-regulatory site whereas 3 position changes may be important for binding specificity. PMID- 4032428 TI - Synthesis and LSD-like discriminative stimulus properties in a series of N(6) alkyl norlysergic acid N,N-diethylamide derivatives. AB - A convenient method for the synthesis of N(6)-alkyl norlysergic acid N,N diethylamide derivatives was developed. A series of these compounds was synthesized and tested for substitution in the two-lever drug discrimination assay, in rats trained to discriminate injections of d-LSD tartrate (185.5 nmol/kg, ip) from saline. A dose-response curve for each of the compounds in the series was generated. Structure-activity relationships were developed, based on comparison of the estimated ED50 values from these curves. Of the compounds that substituted for LSD, the N(6)-ethyl and -allyl were approximately 2-3 times more potent than LSD itself. The N(6)-propyl was equipotent to LSD, while the isopropyl derivative was half as active. The n-butyl compound was 1 order of magnitude less potent than LSD, suggesting a similarity to the SAR of certain serotonin and dopamine agonists. By contrast, no generalization occurred to norlysergic acid N,N-diethylamide and the N(6)-2-phenethyl derivative. PMID- 4032429 TI - Anticonvulsant activity of some 4-aminobenzanilides. AB - A series of 4-aminobenzanilides derived from ring-alkylated anilines were prepared and evaluated for anticonvulsant activity. These benzanilides were prepared in the course of studies designed to determine the relationship between the benzamide structure and anticonvulsant effects. The compounds were tested in mice against seizures induced by electroshock and metrazole (pentylenetetrazole) and in the rotorod assay for neurologic deficit. All of the 4-aminobenzanilides showed activity at doses of 300 mg/kg against maximal electroshock seizures (MES). The 4-aminobenzanilide derived from 2,6-dimethylaniline (8) was the most potent anti-MES compound with an ED50 of 2.60 mg/kg and a protective index of 5.77 (PI = TD50/ED50). The activity profile for 8 compares quite favorably with that for phenobarbital and phenytoin in the same assays. PMID- 4032430 TI - Molecular mechanism of action of 5,6-dihydroxytryptamine. Synthesis and biological evaluation of 4-methyl-, 7-methyl-, and 4,7-dimethyl-5,6 dihydroxytryptamines. AB - The major mechanism by which the serotonin neurotoxin 5,6-dihydroxytryptamine (5,6-DHT) expresses its neurodegenerative action may involve alkylation of biological nucleophiles by the electrophilic quinoid autoxidation products. To determine the relative importance of various sites on these autoxidation products toward alkylation we have rationally designed and synthesized 4-Me-5,6-DHT (16a), 7-Me-5,6-DHT (16b), and 4,7-Me2-5,6-DHT (16c). The indole nucleus of these analogues was constructed by the reductive cyclization of the corresponding 2, beta-dinitrostyrenes, and the aminoethyl side chain was introduced via gramine methiodides. Redox data showed that all the analogues are more readily oxidized compared to 5,6-DHT. The biological activity was evaluated in differentiated neuroblastoma N-2a cells in culture. The order of inhibitory potency, as determined by measuring the inhibition of incorporation of [3H]thymidine into DNA, was 16c much greater than 16a greater than 5,6-DHT approximately equal to 16b. The order of affinity (expressed as IC50 values in microM) for serotonergic uptake as determined by measuring their inhibition of [3H]-5-HT uptake was 5,6 DHT (4) greater than 16c (20) greater than 16a (23) greater than 16b (52). The results of these studies established that these rationally designed C-methylated analogues of 5,6-DHT are suitable probes for elucidating the molecular mechanism of action of 5,6-DHT. PMID- 4032431 TI - Synthesis and structure-activity relationships of a new series of antiarrhythmic agents: 4,4-disubstituted hexahydro-3H-pyrido[1,2-c]pyrimidin-3-ones and related compounds. AB - A series of 4,4-disubstituted tetrahydro- and 4,4-disubstituted hexahydro-3H pyrido[1,2-c]pyrimidin-3-ones (4 and 5, respectively) were prepared from 2-aryl-2 (2-piperidinyl)-4-[N,N-bis (1-methylethyl)amino] butanamides (2). Individual racemates of the piperidinyl amides 2 were converted to pure racemic diaza bicyclic compounds that were evaluated for antiarrhythmic activity in the Harris dog model and anticholinergic activity in a muscarinic receptor binding assay. Selected compounds were subsequently evaluated for hemodynamic effects in anesthetized dogs where blood pressure depression and negative inotropic activity were assessed. Of this group, 4a (R = CH3) and 5a (R = CH3) showed the most favorable pharmacological profiles; the former compound was chosen for toxicity testing over the latter due to its lack of noncompetitive inhibition of acetylcholine-induced contractions of guinea pig ileum segments. Clinical evaluation is now under way. PMID- 4032432 TI - Synthetic and conformational studies on anatoxin-a: a potent acetylcholine agonist. AB - Anatoxin-a is a powerful nicotinic acetylcholine receptor agonist. Its recently reported synthesis has been further optimized to provide anatoxin-a of greater than 99% optical purity in 10% overall yield. The geometry of solid anatoxin-a has been determined by X-ray crystallography of its hydrochloride. The solution conformation has been determined by 500-MHz 1H NMR spectroscopy, utilizing 2D NMR methods and homonuclear decouplings. For further comparisons, force field calculations have been employed to evaluate the differences in energy between the various conformations available for anatoxin-a. The molecule is seen to adopt the same ring conformation both in solution and in the crystal. Comparison of this conformation with the models proposed for acetylcholine receptor activation shows good agreement and allows for further inferences concerning the stereodiscrimination by the receptor. PMID- 4032434 TI - Synthesis of high specific activity [75Br]- and [77Br]bromperidol and tissue distribution studies in the rat. AB - A rapid synthesis of [75Br]- and [77Br]bromperidol with specific activity exceeding 10000 Ci/mmol is described in which a trimethylstannylated analogue of bromperidol is used as a substrate for regiospecific no-carrier-added radiobromination. 4-[4-[4-(Trimethylstannyl)phenyl]-4-hydroxypiperidino]-4'- fluorobutyrophenone was synthesized by the reaction of (trimethylstannyl)sodium with haloperidol and purified by preparative HPLC. Subsequent radiobromination with no-carrier-added 75Br- or 77Br- and in situ oxidation using H2O2/CH3COOH gave a corrected radiochemical yield of 35% with a 30-min preparation time. Tissue distribution studies in the rat show a rapid and prolonged uptake into the brain, liver, and kidneys and consistently low blood concentrations that differ quantitatively from previous studies using relatively low specific activity bromperidol. Potential clinical applications for this high specific activity radiobrominated neuroleptic are discussed. PMID- 4032433 TI - Effects of charge, volume, and surface on binding of inhibitor and substrate moieties to acetylcholinesterase. AB - Reversible inhibitors for acetylcholinesterase, AcChE, have been studied. Sterically similar alcohols with tetra-substituted uncharged beta groups, (CH3)3SiCH2CH2OH (I), (CH3)3CCH2CH2OH (IA), and CH3S(O2)CH2CH2OH (VII), bind similarly, KI = 3-9 mM, and each binds similarly to its acetate substrate; cationic analogues, (CH3)3N+CH2CH2OH (IB) and (CH3)2S+CH2CH2OH (II), bind similarly to each other, KI = 0.4 mM, similar to Km values of their acetate substrates, and more strongly than the uncharged alcohols by approximately 1.5 kcal/mol. In comparisons of VII with CH3SO2CH3, II with (CH3)3S+, and IB with (CH3)4N+, hydroxyethyl leads to more favorable binding than methyl by approximately 0.8 kcal/mol, despite lower hydrophobicity. Two hydrophobic methyl groups, in comparison of IA with butanol, and two hydrophilic sulfone O atoms, in comparison of VII with 2-(methylthio)ethanol, increase binding similarly, by 1.0 kcal/mol. Conversion of (CH3)3S+ to (CH3)3S+O also improves binding. However, (CH3)3N+O- does not bind to AcChE, and conversion of 1-(dimethylammonio)-4 pentanone and 2-(dimethylammonio)ethyl acetate to their N-oxides, changes of identical to N+H to identical to N+--O-, decreases binding by 1.5 kcal/mol. Although the -COCH3 group in esters with well-binding beta substituents makes essentially no contribution to binding over that of the alcohols, in esters with weakly bound beta substituents, (CH3)2N+(O-), CH3N+H2, CH3S(O), CH3CH2, and CH3S binding is dominated by the ester -COCH3 group, with values of Km approximately 16 mM. PMID- 4032435 TI - New cysteamine (2-chloroethyl)nitrosoureas. Synthesis and preliminary antitumor results. AB - Three chemical pathways were used for the synthesis of four new N'-(2 chloroethyl)-N-[2-(methylsulfinyl)ethyl]- and N'-(2-chloroethyl)-N-[2 (methylsulfonyl)ethyl]-N- or N'-nitrosoureas. These compounds are plasma metabolites of CNCC, a promising antineoplastic (2-chloroethyl)nitrosourea. Preliminary antitumor evaluation was performed against L1210 leukemia implanted intraperitoneally in mice. Among these compounds, two of them exhibited a greater antitumor activity compared to that of the parent mixture. PMID- 4032437 TI - Aminotetralone analogues of ketamine: synthesis and evaluation of hypnotic and locomotor properties in mice. AB - Ketamine and phencyclidine are structurally similar compounds that share many pharmacological actions, some of which are similar to the phenethylamines amphetamine and cathione. In order to integrate structural features of ketamine and cathinone, two groups of analogues, which are more conformationally restricted compared to the parent compounds, were synthesized for biological evaluation. These included 1-amino-1-methyl-2-tetralone and 2-amino-2-methyl-1 tetralone was well as several N-substituted derivatives of these molecules. Locomotor activity testing in mice revealed that 2-amino-2-methyl-1-tetralone caused an increase in locomotor activity while 1-amino-1-methyl-2-tetralone depressed spontaneous locomotor activity. None of the compounds produced hypnosis or profound ataxia. PMID- 4032436 TI - In the search for new anticancer drugs. 13. Phosphonic and phosphinic analogues of ornithine. AB - Phosphonic (4a,b) and phosphinic (5a-d) analogues of ornithine were synthesized and evaluated for their inhibitory activity against ornithine decarboxylase and against the lymphocytic leukemia P388. The title compounds possess a low degree of inhibition against rat liver ornithine decarboxylase as compared to alpha (difluoromethyl)ornithine. Thus, compounds 4a and 5a inhibit by 40% the ornithine decarboxylase activity at a 5 mM concentration. The other derivatives are less potent. Compounds 4a, 4b, 5b, and 5d are inactive against P388 tumor in CD2F1 mice at doses of 50 and 150 mg/kg. PMID- 4032438 TI - Analogues of platelet activating factor. 3. Replacement of the phosphate moiety with a sulfonylbismethylene group. AB - An analogue of platelet activating factor (PAF) in which the phosphate moiety has been replaced with a sulfonylbismethylene group has been prepared. A key step in the synthetic sequence is the preparation of 4-[[3-(dimethylamino)propyl]thio]-1 (hexadecyloxy)-2-butanol via a one-pot reaction involving a sequential Michael addition and reduction. In comparison to racemic C16-PAF, 8 showed no platelet aggregating activity and substantially reduced hypotensive activity. PMID- 4032440 TI - Impact on academic medical center of reduction in reimbursement of indirect research costs. AB - Debate over the level of indirect cost reimbursement associated with federally funded research projects continues to grow. With the increasing federal budget restraints, one recurring proposal arising from federal legislators, the executive branch, and the National Institutes of Health to cut costs and sustain direct project support has been to reduce indirect cost reimbursement. Using a system dynamics simulation model, the authors in this paper analyze the long-term economic impacts of such cutbacks on an academic medical center. The significant negative multiplier effects, due to the required diversion of institutional funds, are indicative of those that any research oriented university would experience. PMID- 4032439 TI - Preparation of biologically active ristocetin derivatives: replacements of the 1' amino group. AB - A series of ristocetin analogues with modifications (OH, C=O, C=NOH, NCOCH3) at the C-1' amino group was synthesized and found to possess antibacterial activity against gram-positive bacteria and to bind to Ac2-Lys-D-Ala-D-Ala, a model for the antibiotic's site of action. Due to the lack of a positively charged amino group, the active analogues could not form a salt bridge, indicating that an electrostatic interaction between the positively charged 1'-amino group of ristocetin and the carboxylate anion of the peptide is not required for complex formation. The only compound that did not exhibit good antibacterial activity was epiristocetin aglycone (an analogue with the 1'amino group in the opposite configuration (S) as ristocetin). On the basis of NMR studies of epiristocetin aglycone in solution, the 1'-amino group is located in the proposed carboxylate binding pocket and may sterically block complex formation. PMID- 4032441 TI - Course work and grades of premedical students at two liberal arts colleges. AB - Choices of courses and academic performances of premedical students were investigated at two liberal arts colleges. Four hypotheses tested related to the areas of science concentration in the students' overall academic programs, breadth of the programs, depth of study in subjects outside science, and the grades achieved in all areas. Altogether, 345 students from the classes of 1982 and 1983 were studied. Premedical students were compared with nonpremedical students studying biology and chemistry and with all other students. Premedical students and other students majoring in biology, chemistry, or other health related subjects had similar distributions of course credits by academic division and studied a greater breadth of subject matter than did other students. In contrast, the other students tended to study one subject outside their major in greater depth than the premedical students and other students majoring in biology and chemistry, and these subjects were usually in an academic division that did not include their major departments. The students from the two colleges who were admitted to medical schools achieved higher grades than either rejected applicants or nonapplicants from the colleges. PMID- 4032442 TI - Impact of medical school class ranking systems on applicants' ratings for residency positions. AB - The systems used by the medical schools for evaluation of 106 applicants for 1984 85 pediatric level 1 (PL-1) residency positions at the Duke University Medical Center were studied by the authors to determine the possible relationship between contents of the applications and the rankings of these applicants for the National Resident Matching Program (NRMP). In the 56 U.S. medical schools studied, the grading systems of 24 medical schools used three passing grades (usually A, B, C), 14 used two passing grades (usually honors and pass), six used one passing grade (pass) and seven used a mixed system or number grades. The grading systems of five schools could not be discerned. Ten schools provided the class distribution of the awarded grades, and 23 identified the relative class standing of the applicant. Twenty-seven schools disclosed the position of the applicant in the class through grade distribution data or class standing; the 29 other schools did not make such information known. Students whose schools had identified their class positions achieved higher rankings from the residency selection committee than did students from schools which did not, in spite of the fact that schools which did not disclose the student's comparative positions were categorized as being more "distinguished." PMID- 4032443 TI - Teaching the history of medicine to medical students. AB - The author in this article advocates the teaching of the history of medicine to medical students throughout their undergraduate medical education. The thesis is that teaching the history of medicine enhances the development of the student into a physician and supports his technical training. History acts as a unifying force connecting a variety of scientific and humanistic disciplines and, by providing a historical perspective, serves to promote the student as a professional. PMID- 4032445 TI - Substance-abuse education in medical school: past, present, and future. AB - In this article, the author presents an overview of substance-abuse education in U.S. medical schools. In the early 1970s, two nationwide conferences prompted an awareness of the need for improved medical education in substance abuse. The Council on Mental Health and the Committee on Alcohol and Drug Dependency, both of the American Medical Association, presented general guidelines for a curriculum in substance abuse. During the same era, the federal government sponsored a career teacher training program in drug abuse and alcoholism, and private foundation funding supported educational endeavors that resulted in long term materials for teaching in medical schools. Three current programs that are improving drug-abuse education are described. These developments are good examples of efforts that should be considered for any medical school curriculum. Goals for the future should include some attempt to modify the institutions, both medical schools and hospitals, where patterns leading to physician impairment may develop. PMID- 4032444 TI - Practice location preferences of Alabama medical students. AB - Factors that help determine physicians' practice locations and specialties were listed by 396 students and 103 medical school faculty members at the University of Alabama School of Medicine. The students preferred practice locations similar in size to their hometowns. Their specialty choices were closely related to both practice location preferences and hometown sizes. However, there was a tendency among the students to prefer a small city (20,000 to 100,000 population) practice location irrespective of their hometown sizes or specialty choices. Factors such as spouse's preference, proximity of relatives, and financial incentives were not related to the students' practice location preferences. Faculty members reported they believed that medical education biases students toward urban and nonprimary care practice, and one-third of them said that they were role models for the students' specialty choices. However, the students said faculty members had little influence on their specialty choices while acknowledging the importance of clinical experiences. In general, Alabama medical students are similar to medical students elsewhere with respect to determinants of practice location preference. PMID- 4032446 TI - Significant attitude changes among residents associated with a pediatric nurse practitioner. AB - In the study reported here, significant changes in attitudes occurred over a three-year period among pediatric residents who had close association with a pediatric nurse practitioner (PNP) in their residency program. Residents entering the training program had an overall uncertain attitude toward PNPs but did respond favorably to the PNP's participation in the care of well children, patient education, and follow-up care. The greatest number of attitude changes toward the PNP took place after the first year of interaction between the residents and the PNP. After the first year, the residents favored the PNP's participation in the care of minor illnesses and stable chronic illnesses and in management of telephone calls from parents with concerns. Second-year residents also felt that the PNP was accepted by patients and physicians, that the PNP contributed to the reduction of health care costs, and that the PNP should have an expanded role. Upper-level residents continued to express favorable attitudes. The findings support the authors' hypothesis that favorable attitudes on the part of physicians toward PNPs can be cultivated during residency training by exposing residents to a PNP role model. In addition, the findings suggest that subsequent years of exposure will reinforce these favorable opinions if favorable opinions are established early in residency training. PMID- 4032447 TI - Relationship between subject examination scores in clerkships and academic and demographic factors. PMID- 4032448 TI - The influence of noncognitive variables in student performance. PMID- 4032449 TI - Gaining knowledge of geriatric medicine in the medicine clerkship. PMID- 4032450 TI - A self-assessment questionnaire for patient educators. PMID- 4032452 TI - To rank or not to rank. PMID- 4032451 TI - Effect of a breast examination teaching unit in physical diagnosis on medical students' practices. PMID- 4032453 TI - Restoration of immunosuppression in lung cancer by normal sera. AB - The ConA and PWM responses of blood lymphocytes from lung cancer patients (LC) was found to be diminished in comparison to normal. LC sera inhibited the blastogenic response of normal human and rat lymphocytes, suggesting that there is a common inhibitory mechanism. Addition of normal serum to lung cancer blood lymphocytes allows a restoration of the diminished proliferative responses to normal or near normal levels, except to high ConA concentrations. Possible explanations for this finding are discussed. PMID- 4032454 TI - Preparation of antibodies against the fourth complement component (C4) and development of a direct electroimmunoassay for quantification of C4d. AB - The specificity of several preparations of antihuman C4 antibodies were examined by crossed immunoelectrophoresis. Two antibody preparations with anti-C4c and anti-"total" C4 reactivity respectively were prepared by immunoadsorption procedures and defined by comparison with reference antibodies of known specificity. These two antibody preparations were used in the development of a rocket immunoelectrophoresis with an intermediate gel for specific and direct quantification of C4d. This method permits the selective quantification of activation of the classical complement pathway as opposed to the alternative pathway activation. PMID- 4032455 TI - Apparent activation volumes of hydrophobic ions and carriers in planar lipid bilayers. AB - A gas-free high-pressure cell has been developed to measure planar bilayer conductances induced by hydrophobic ions and ionophores as a function of hydrostatic pressure. Plots of log conductance versus pressure for valinomycin and nonactin-mediated potassium transport in egg phosphatidyl cholinedecane membranes are essentially linear over a pressure range of 1 to 818 atm. Calculated activation volumes give similar results for both nonactin and valinomycin yielding values of + 48 and + 42 cc/mole, respectively. The valinomycin activation volume agrees reasonably well with the results obtained by Johnson and Miller (Biochim. Biophys. Acta 375:286-291, 1975) for K+-valinomycin transport in liposomes. In contrast to the activation volumes for nonactin and valinomycin, relaxation measurements of tetraphenyl boron (TPB) and dipicrylamine (DPA) give very small values of less than 5 cc/mole for the translocation rate constant, ki. Similarly, steady-state conductance measurements on tetraphenyl arsonium (TPA) and carbonylcyanide m-chlorophenylhydrazone (CCCP), give small values of 6 and 7 cc/mole, respectively. These low figures do not support transport theories based on the formation of bilayer holes or kinks (H. Trauble, J. Membrane Biol. 4:193-208, 1971). The low values for TPB and TPA are especially interesting because their cross-sectional areas are not much different than those of valinomycin and nonactin. Pressure-induced changes in membrane dielectric constant and thickness which lower the bilayer electrostatic barrier could explain the low values for the hydrophobic ions. Additionally, larger activation volumes might be expected for carriers such as nonactin and valinomycin that undergo significant rearrangement and change in hydration during surface complexation of cations. PMID- 4032456 TI - Cyanine dye fluorescence used to measure membrane potential changes due to the assembly of complement proteins C5b-9. AB - The fluorescent potentiometric indicator diS-C3-(5) has been used to investigate changes in membrane potential due to assembly of the C5b-9 membrane attack complex of the complement system. EAC1-7 human red blood cells and resealed erythrocyte ghosts--bearing membrane-assembled C5b67 complexes--were generated by immune activation in C8-deficient human serum. Studies performed with these cellular intermediates revealed that the membrane potential of EAC1-7 red cells and ghosts is unchanged from control red cells (-7 mV) and ghosts (O mV), respectively. Addition of complement proteins C8 and C9 to EAC1-7 red cells results in a dose-dependent depolarization of membrane potential which precedes hemolysis. This prelytic depolarization of membrane potential--and the consequent onset of hemolysis--is accelerated by raising external [K+], suggesting that the diffusional equilibration of transmembrane cation gradients is rate limiting to the cytolytic event. In the case of EAC1-7 resealed ghosts suspended at either high external [K+] or [Na+], no change in membrane potential (from O mV) could be detected after C8/C9 additions. When the membrane potential of the EAC1-7 ghost was displaced from O mV by selectively increasing the K+ conductance with valinomycin, a dose-dependent depolarization of the membrane was observed upon addition of C8 and C9. In these experiments, lytic breakdown of the ghost membranes was less than 5%. Conclusions derived from this study include: (i) measured prelytic depolarization of the red cell Donnan potential directly confirms the colloid-osmotic theory of immune cytolysis. (ii) The diffusional transmembrane equilibration of Na+ and K+ through the C5b-9 pore results in a dose-dependent depolarization of the membrane potential (Em) which appears to be rate-limiting to cytolytic rupture of the target erythrocyte. (iii) Enhanced immune hemolysis observed in high K+ media cannot be attributed to cation selective conductance across the C5b-9 pore, and is probably related to the near equilibrium condition of potassium-containing red cells when suspended at high external K+. These experiments demonstrate that carbocyanine dye fluorescent indicators can be used to monitor electrochemical changes arising from immune damage to the plasma membrane under both cytolytic and noncytolytic conditions. Potential application of this method to the detection of sublytic pathophysiological changes in the plasma membrane of complement-damaged cells are discussed. PMID- 4032458 TI - Measurement and stoichiometry of bumetanide-sensitive (2Na:1K:3Cl) cotransport in ferret red cells. AB - The bumetanide-sensitive uptake of Na+, K+(Rb+) and Cl- has been measured at 21 degrees C in ferret red cells treated with (SITS + DIDS) to minimize anion flux via capnophorin (Band 3). During the time course of the influx experiments tracer uptake was a first-order rate process. At normal levels of external Na+ (150 mM) the bumetanide-sensitive uptake of K+ was dependent on Cl- and represented almost all of the K+ uptake, the residual flux demonstrating linear concentration dependence. The uptake of Na+ and Cl- was only partially inhibited by bumetanide indicating that pathways other than (Na + K + Cl) cotransport participate in these fluxes. The diuretic-sensitive uptake of Na+ or Cl- was, however, abolished by the removal of K+ or the complementary ion indicating that bumetanide sensitive fluxes of Na+, K+ and Cl- are closely coupled. At very low levels of [Na]o (less than 5 mM) K+ influx demonstrated complex kinetics, and there was evidence of the unmasking of a bumetanide-sensitive Na+-independent K+ transport pathway. The stoichiometry of bumetanide-sensitive tracer uptake was 2Na:1K:3Cl both in cells suspended in a low and a high K+-containing medium. The bumetanide sensitive flux was markedly reduced by ATP depletion. We conclude that a bumetanide-sensitive cotransport of (2Na:1K:3Cl) occurs as an electroneutral complex across the ferret red cell membrane. PMID- 4032457 TI - Permeability properties of cell-to-cell channels: kinetics of fluorescent tracer diffusion through a cell junction. AB - We have analyzed the intracellular and cell-to-cell diffusion kinetics of fluorescent tracers in the Chironomus salivary gland. We use this analysis to investigate whether membrane potential-induced changes in junctional permeability are accompanied by changes in cell-to-cell channel selectivity. Tracers of different size and fluorescence wavelength were coinjected into a cell, and the fluorescence was monitored in this cell and an adjacent one. Rate constants, kj, for cell-to-cell diffusion were derived by compartment model analysis, taking into account (i) cell-to-cell diffusion of the tracers; (ii) their loss from the cells; (iii) their binding (sequestration) to cytoplasmic components; and (iv) their relative mobility to cytoplasm, as determined separately on isolated cells. In cell pairs, we compared a tracer's kj with the electrical cell-to-cell conductance, gj. At cell membrane resting potential, the kj's ranged 3.8-9.2 X 10(-3) sec-1 for the small carboxyfluorescein (mol wt 376) to about 0.4 X 10(-3) sec-1 for a large fluorescein-labeled sugar (mol wt 2327). Cell membrane depolarization reversibly reduced gj and kj for a large and a small tracer, all in the same proportion. This suggests that membrane potential controls the number of open channels, rather than their effective pore diameter or selectivity. From the inverse relation between tracer mean diameter and relative kj we calculate an effective, permeation-limiting diameter of approximately 29 A for the insect cell to-cell channel. Intracellular diffusion was faster than cell-to-cell diffusion, and it was not solely dependent on tracer size. Rate constants for intracellular sequestration and loss through nonjunctional membrane were large enough to become rate-limiting for cell-to-cell tracer diffusion at low junctional permeabilities. PMID- 4032459 TI - Calcium at the surface of cardiac plasma membrane vesicles: cation binding, surface charge screening, and Na-Ca exchange. AB - Calcium binding and Na-Ca exchange activity were measured in isolated cardiac plasma membrane vesicles under various ionic conditions. A model was developed to describe the Ca binding characteristics of cardiac sarcolemmal vesicles using the Gouy-Chapman theory of the diffuse double layer with specific cation binding to phospholipid carboxyl and phosphate groups. The surface association constants used for Ca, Na, K and H binding to both of these groups were 7,0.63, 0.3 and 3800 M-1, respectively. This model allows the estimation of surface [Ca] under any specific ionic conditions. The effects of the divalent screening cation, dimethonium, on Ca binding and Na-Ca exchange were compared. Dimethonium had no significant effect on Ca binding at high ionic strength (150 mM KCl), but strongly depressed Ca binding at low ionic strength. Dimethonium had no significant effect on Na-Ca exchange (Na-inside dependent Ca influx) at either high or low ionic strength. These results suggest that the Ca sites of the Na-Ca exchanger are in a physical environment where they are either not exposed to or not sensitive to surface [Ca]. PMID- 4032460 TI - Tight junction formation in cultured epithelial cells (MDCK). AB - Synthesis and assembly of tight junctions are studied in monolayers of MDCK cells plated at a density sufficient for confluence, allowed to attach for 1 hr, and transferred to fresh media without cells containing or not Ca2+. 20 hr later, while monolayers with Ca2+ have fully developed junctions that confer an electrical resistance across of 346 +/- 51 omega cm2, those without Ca2+ have a negligible resistance. If at this time Ca2+ is added, junctions assemble and seal with a fast kinetics, that can be followed through the development of electrical resistance, penetration of ruthenium red, and electron microscopy. Drugs that impair synthesis, maturation and transport of proteins (cycloheximide, tunicamycin, monensin) indicate that protein components are synthesized early upon plating, do not seem to require N-glycosylation, and are stored in the Golgi compartment. Upon addition of Ca2+ they are transferred to the membrane with the participation of microfilaments but not of microtubules. These components seem to insert directly in the position they occupy in the strands, and the cell circles its perimeter with one strand as early as 15 min, even if in some segments it only consists of a row of particles. New strands develop in association with previous ones, and the pattern completes in 4 to 6 hr. Ca2+ is required for the maintenance of the assembly and also for the sealing with neighboring cells. These processes cannot occur below 25 degrees C. Serum is not required. Polarized distribution of intramembrane particles (IMP) in apical and basolateral regions follows the same time course as junction formation, in spite of the fence constituted by those strands that are already assembled. This suggests that IMP do not redistribute by lateral displacements in the plane of the membrane, but by removal and insertion in the apical and basolateral domains. PMID- 4032461 TI - A minimum mechanism for Na+-Ca++ exchange: net and unidirectional Ca++ fluxes as functions of ion composition and membrane potential. AB - Both simultaneous and consecutive mechanisms for Na+-Ca++ exchange are formulated and the associated systems of steady-state equations are solved numerically, and the net and unidirectional Ca++ fluxes computed for a variety of ionic and electrical boundary conditions. A simultaneous mechanism is shown to be consistent with a broad range of experimental data from the squid giant axon, cardiac muscle and isolated sarcolemmal vesicles. In this mechanism, random binding of three Na+ ions and one Ca++ on apposing sides of a membrane are required before a conformational change can occur, translocating the binding sites to the opposite sides of the membranes. A similar (return) translocation step is also permitted if all the sites are empty. None of the other states of binding can undergo such translocating conformational changes. The resulting reaction scheme has 22 reaction steps involving 16 ion-binding intermediates. The voltage dependence of the equilibrium constant for the overall reaction, required by the 3:1 Na+: Ca++ stoichiometry was obtained by multiplying and dividing, respectively, the forward and reverse rate constants of one of the translocational steps by exp(-FV/2RT). With reasonable values for the membrane density of the enzyme (approximately 120 sites micron 2) and an upper limit for the rate constants of both translocational steps of 10(5) . sec-1, satisfactory behavior was obtainable with identical binding constants for Ca++ on the two sides of the membrane (10(6) M-1), similar symmetry also being assumed for the Na+ binding constant (12 to 60 M-1). Introduction of order into the ion-binding process eliminates behavior that is consistent with experimental findings. PMID- 4032463 TI - Developmental trends of jumping reaction time by means of EMG in mentally retarded children. AB - Developmental trends of jumping reaction time (RT) in mentally retarded children were studied cross-sectionally. Fifty-three boys, ranging in CA from 7 to 18 years, took part in the jumping RT task. RT measurements were obtained from EMG of an agonist muscle (rectus femoris). There was a significant decrease in RT with increasing CA. Correlation between RT and MA was highly significant, but discontinuity in the distribution was found between MA of 6 and 7 years. The subjects with a MA below 6 were characterized by large variability as well as slowness in RT. RT was not correlated with CA holding MA constant among the subjects with a MA below 6. The subjects with a MA above 7 showed relatively small variability within and between subjects. RT in subjects with a MA above 7 decreased with CA holding MA constant but RIV showed no change. RT in children with a very low MA is prolonged by inefficiency which reflects difficulty in maintaining attention or arousal level. The efficiency in information processing may change between the MAs of 6 and 7 years. PMID- 4032462 TI - Barium modifies the concentration dependence of active potassium transport by insect midgut. AB - The rate of active K+ transport by the isolated lepidopteran midgut shows a rectangular hyperbolic relation to [K+] over the range 20 to 70 mM K+ in the absence of any divalent cation. Addition of Ba++ to the hemolymph (K+ uptake) side introduces a linear component to the concentration dependence, such that active K+ transport is decreased at [K+] of 55 mM or less, but increased transiently at higher [K+]. As [Ba++] is increased over the range 2 to 8 mM the linear component increases and the saturating component decreases; in 8 mM Ba++ the concentration dependence is dominated by the linear component. The effect of Ba++ cannot easily be accounted for by simple competition with K+ for basal membrane uptake sites. Similar effects might be exercised by other alkali earth cations, since the concentration dependence of active K+ transport possesses a substantial linear component in solutions containing 5 mM Ca++ and 5 mM Mg++ (the alkali earth metal concentrations of standard lepidopteran saline). PMID- 4032464 TI - Verb usage by educable mentally retarded children. AB - The purpose of this study was to investigate the semantic and morphological nature of verb usage by educable mentally retarded (EMR) children. Three groups of children were studied in structured and non-structured situations in which the verb system was the core interest. There were 15 mentally retarded younger children (8.6-9.6 years), 19 mentally retarded older children (10.0-12.6 years) and a control group of 17 normal children (5.0-6.0 years). Results showed that EMR children use fewer conjugations than normal children of similar or lower mental age, and thus they can express fewer verb-case relations. In particularly EMR children show limited use of process-verb relations. It was further found that EMR children are restricted in the morphological processing of verbs in past and future tenses. PMID- 4032466 TI - X-ray microscopy: experimental results with the Gottingen X-ray microscope at the electron storage ring BESSY in Berlin. AB - An X-ray microscope and X-ray microscopy experiments with biological specimens are described. The experiments have been performed with a resolution of about 0.05 micron using the synchrotron radiation of the electron storage ring BESSY. PMID- 4032465 TI - Finnish type of sialic acid storage disease with sialuria (Salla disease): the occurrence and diagnostic significance of cytoplasmic vacuoles in blood lymphocytes. AB - In this study peripheral blood smears from 29 patients (17 males and 12 females; mean age 28 years, range 3-65 years) with a confirmed diagnosis of the Finnish type of sialic acid storage disease (FSASD) and 200 controls with mental retardation without any evidence of metabolic disease were examined for the presence of vacuolated lymphocytes. Urine samples were analysed by thin-layer chromatography for free sialic acid. Only 62% of the patients with FSASD had a clearly increased percentage of vacuolated lymphocytes (greater than normal mean + 2 s.d.). In thin-layer chromatography all the FSASD patients gave a positive test result. No false positive or negative results were obtained. Electronmicroscopical examination of peripheral blood lymphocytes demonstrated only non-specific changes in a few cells. Examination of peripheral lymphocytes for vacuoles is not a reliable screening test for FSASD. The screening method of choice is the analysis of free sialic acid by thin-layer chromatography. PMID- 4032467 TI - Synchrotron radiation applied to the microscopical examination of solid state and biological materials in the X-ray region. AB - The paper describes the properties of synchrotron radiation and makes some comparison with other X-ray sources. The use of synchrotron radiation for various types of X-ray imaging is discussed with reference to specific examples drawn from work carried out recently at the SERC Daresbury Laboratory. PMID- 4032468 TI - Developments in contact X-ray microscopy in biomedical research. AB - Contact X-ray microscopy (microradiography) is a method of studying the microstructure of biological tissue. These techniques have been used to study the historadiological details of human breast tissue and sections of human ear ossicles. X-ray microscopy can also be used to demonstrate variations in structural densities seen in histological specimens including the detection of microcalcification. A modification of existing apparatus is described which has resulted in improved image-contrast and detail. The ability of X-rays to penetrate relatively thick sections of tissue makes it an ideal method for studying the morphology of biological structures, particularly in calcified tissue. The tissues may be further examined by conventional histology, elemental analysis, etc. The technique has a complementary role to alternative methods of tissue microscopy. PMID- 4032469 TI - Absorption microanalysis with a scanning soft X-ray microscope: mapping the distribution of calcium in bone. AB - This article describes the scanning transmission X-ray microscope operated at the National Synchroton Light Source. The application of the instrument to elemental analysis is detailed. In particular, qualitative results on the calcium distribution in human skull tissue are presented. PMID- 4032470 TI - X-ray microscopy using computerized axial tomography. AB - Computerized axial tomography with MoK alpha X-radiation has been used to study a 0.8 X 0.8 mm column of human femoral bone at a resolution of 15 micron. This non destructive X-ray microscopic technique allowed 'sections' to be made with 25 micron separation and the distribution of linear absorption coefficient in each section to be determined. PMID- 4032471 TI - Assessment of coping efficacy: a comment. PMID- 4032472 TI - An empirical examination of the "pain-behavior" construct. AB - Observable means of communicating pain and suffering, "pain behaviors," have been postulated to comprise an important construct relevant in both the development and the maintenance of chronic pain [Fordyce, W.E. (1976). Behavioral Methods for Chronic Pain and Illness, C.V. Mosby, St. Louis, Mo.]. Two groups of professionals who have direct contact with chronic-pain patients (i.e., physicians and psychologists) participated in a study designed (a) to identify the latent or underlying characteristics of pain behaviors and (b) to assess the degree of agreement of these characteristics between health professionals with very different training. Multi-dimensional scaling and hierarchical clustering statistical techniques were employed to identify the latent structure of pain behaviors. Two primary pain behavior dimensions were identified, namely, audible visible and affective-behavioral. Four clusters of pain behaviors were identified and labeled distorted ambulation or posture, negative affect, facial/audible expressions of distress, and avoidance of activity. The two samples of health care providers identified virtually equivalent latent characteristics of pain behaviors. The data suggest that there is consistency in the pain-behavior construct and that the latent structure is generally congruent with Fordyce's original conceptualization. The results provide an empirically derived basis for the assessment of pain behaviors. PMID- 4032473 TI - Coping with a stressful medical procedure: further investigation with volunteer blood donors. AB - The coping strategies used by volunteer blood donors were studied in an attempt to replicate and extend the findings of Kaloupek et al. [(1984). J. Behav. Med. 7:35-60]. Specifically, coping was assessed by process, state, and trait measures that were then examined in terms of their relationships with subjective, physiological, and behavioral indices of anxiety. Ratings of anxiety made by the donors themselves and by attending nurses generally replicated the previous finding of lower distress associated with avoidant coping (e.g., distraction). Problem-focused coping was also associated with lower distress, including a lower heart rate for first-time donors. Other evidence suggests that for some individuals the expression of distress may be part of a coping strategy that is associated with reduced physiological responding. Discussion concerns links between coping and anxiety which may have relevance to stressful medical situations, including the possible need for anxiety reduction to allow successful application of avoidant coping. PMID- 4032475 TI - The continent ileal urinary reservoir: a significant advance in urinary diversion. PMID- 4032474 TI - Stress-induced muscular activity in mandibular dysfunction: effects of biofeedback training. AB - Surface electromyographic (EMG) recordings from the left and right masseteric areas during physical and psychological induced stress were obtained from 20 patients with mandibular dysfunction and 20 healthy controls. Integrated electromyographic activity was not significantly different for the two sides but was higher for patients than for controls during both stress and relaxation. Anxiety level, as measured with the Taylor Manifest Anxiety Scale, was higher for patients. Biofeedback treatment for the patients resulted in significantly reduced signs and symptoms of mandibular dysfunction. When the test procedures were repeated, the controls had not changed in their electromyographic responses during stress, whereas the patients showed a significant decrease in this respect. The results obtained are discussed in terms of a systems-oriented etiological concept. PMID- 4032476 TI - Refinement of a molecular model for lamprey hemoglobin from Petromyzon marinus. AB - A molecular model for the protein and ambient solvent of the complex of cyanide with methemoglobin V from the sea lamprey Petromyzon marinus yields an R-factor of 0.142 against X-ray diffraction data to 2.0 A resolution. The root-mean-square discrepancies from ideal bond length and angle are, respectively, 0.014 A and 1.5 degrees. Atoms that belong to planar groups deviate by 0.012 A from planes determined by a least-squares procedure. The average standard deviation for chiral volumes, peptide torsion angle and torsion angles of side-chains are 0.150 A3, 2.0 degrees and 19.4 degrees, respectively. The root-mean-square variation in the thermal parameters of bonded atoms of the polypeptide backbone is 1.21 A2; the variation in thermal parameters for side-chain atoms is 2.13 A2. The model includes multiple conformations for 11 side-chains of the 149 amino acid residues of the protein. We identify 231 locations as sites of water molecules in full or partial occupancy. The sum of occupancy factors for these sites is approximately 154, representing 28% of the 550 molecules of water within the crystallographic asymmetric unit. The environment of the heme in the cyanide complex of lamprey methemoglobin resembles the deoxy state of the mammalian tetramer. In particular, the bond between atom NE2 of the proximal histidine and the Fe lies 5.1 degrees from the normal of the heme plane. In deoxy- and carbonmonoxyhemoglobins, the deviations from the normal to the heme plane are 7 to 8 degrees and 1 degree, respectively. Furthermore, the inequality in the distance of atom CD2 of the proximal histidine from the pyrrole nitrogen of ring-C of the heme (distance = 3.29 A) and CE1 from the pyrrole nitrogen of ring-A (distance = 3.06 A) is characteristic of deoxyhemoglobin, not carbonmonoxyhemoglobin, where these distances are equal. Finally, a hydrogen bond exists between carbonyl 111 and the hydroxyl of tyrosine 149. The corresponding hydrogen link in the mammalian tetramer is central to the T to R state transition and is present in deoxyhemoglobin but absent in carbonmonoxyhemoglobin. We suggest that the low affinity of oxygen for lamprey hemoglobin may be a consequence of these T-state geometries. PMID- 4032477 TI - Preliminary crystallographic study of an L-asparaginase from Vibrio succinogenes. AB - Crystals of an L-asparaginase from Vibrio succinogenes were obtained with the hanging drop method from ammonium sulphate-containing solutions. The crystals belong to the orthorhombic space group P22(1)2(1) with unit cell dimensions of a = 71.3 A, b = 85.8 A, c = 114.0 A, and contain two tetrameric enzyme molecules per unit cell. There are two subunits in the asymmetric unit; a molecular dyad is coincident with the crystallographic dyad. The crystal lattice is similar to that reported for an Escherichia coli asparaginase. Rotation function calculations have revealed that the V. succinogenes enzyme has 222 point group symmetry in the crystal. The second and third molecular dyads differ, however, from the corresponding E. coli asparaginase dyads by approximately 40 degrees. The crystals diffract to at least 2.2 A resolution and are suitable for X-ray crystallographic structure determination. PMID- 4032478 TI - Signal sequences. The limits of variation. AB - Variations in length and composition of the charged N-terminal, central hydrophobic and polar C-terminal regions in a large sample of signal sequences have been mapped, both as a function of the overall length of the sequence, and in an absolute sense, i.e. various "extremes" have been sought. The results show subtle differences between eukaryotic and prokaryotic sequences, but the general impression of signal sequences as being highly variable is reinforced. Criteria for a "minimal" signal sequence are suggested and discussed. PMID- 4032479 TI - Triple rings: a new type of compact structure of circular DNA. AB - Complexes of circular superhelical pBR322 DNA with a synthetic tripeptide capable of beta-structure formation (dansylhydrazide trivaline) were studied at different peptide/DNA ratios by electron microscopy. It was shown on rotary-shadowed preparations that peptide binding induces intramolecular DNA condensation and compact ring-shaped particles are formed from fibres 120 A thick. The analysis of the morphology of the ring structures observed at various peptide/DNA ratios as well as contour length measurements enabled us to draw conclusions about the organization of the double-stranded DNA filaments in these structures. It was established that the fibres forming compact rings contain three double-stranded DNA segments closely associated due to DNA-peptide and peptide-peptide interactions. The mechanisms leading to the formation of the triple rings may be important in DNA condensation in vivo. PMID- 4032480 TI - Low resolution crystal structure of muconolactone isomerase. A decamer with a 5 fold symmetry axis. AB - Muconolactone isomerase from Pseudomonas putida crystallizes from sodium sulfate solution in space group P2(1) (a = 65.84 A, b = 105.70 A, c = 77.20 A, beta = 90.5 degrees) with ten 11,000 Mr subunits per asymmetric unit. The 7 A resolution crystal structure was solved by single isomorphous replacement followed by 10 fold symmetry averaging. The decameric enzyme has an uncommon non crystallographic 5-fold symmetry axis and a large cavity in its center. PMID- 4032481 TI - Statistical mechanics of DNA topoisomers. The helical worm-like chain. AB - Recent experimental data of Shore & Baldwin (1983b) and of Horowitz & Wang (1984) for the apparent twisting coefficient K, which determines the breadth of the Gaussian distribution of DNA topoisomers with different linking numbers N, show that the product of K and nbp (the number of base-pairs) is nearly a constant for nbp approximately greater than 2000, but that it increases sharply with decreasing nbp for nbp approximately less than 2000. The main purpose of the present paper is to explain theoretically such behavior of K as a function of nbp. Thus the statistical mechanics of DNA topoisomers in general is developed on the basis of a twisted worm-like chain, i.e. a special case of the helical worm like chain. The previous treatments of the N-dependent ring-closure probability, i.e. the distribution of N, which are valid only for small chain length L, are extended to the range of larger L. The variance of N is then shown to be exactly the sum of those of the writhe Wr and the twist Tw. For small values of L, the distribution of Wr is not Gaussian, and its variance or moment (Wr2) increases rather steeply with increasing L. With these and known Monte Carlo results for freely jointed chains, an empirical interpolation formula for (Wr2) is also constructed to be valid for all values of L. It predicts that (Wr2)/L increases monotonically, with increasing L to its coil-limiting value. On the other hand, the distribution of N is actually Gaussian in the practical range of N for all values of L. The conditional distribution of Wr with N fixed is also evaluated. Finally, K is expressed in terms of the torsional constant C, the stiffness parameter lambda-1 (which is equal to the Kuhn segment length and twice the persistence length for this special case), and (Wr2). The derived equation predicts that nbpK decreases monotonically to its coil-limiting value with increasing nbp. This decrease arises from the fluctuation in Wr and its neglect leads to an underestimate of C by 7 to 10%, even for short DNA with nbp approximately equal to 200. From an analysis of the experimental data of the two groups, the estimates of C = 3.1 to 3.2 X 10(-19) erg cm and lambda-1 = 1000 to 1200 A are obtained. PMID- 4032482 TI - Abstracts of the Sixth Meeting of the Australian and New Zealand Section of the International Society for Heart Research. Lorne, Victoria, Australia, 20-22 February 1985. PMID- 4032483 TI - Mitotic-cyclic and cycle-independent growth of cardiomyocytes. AB - The number of myocytes in mouse heart ventricles increased by 25% to 30%, on average, mainly for 3 days after birth. The mean myocyte number was 1.87 +/- 0.04 X 10(6) in 3-week-old and older mice, while the individual values varied up to 25% in any age group. In newborn mice, up to 90% of the myocytes were diploid cells, then polyploidization occurred. The stable ratio of ploidy classes was observed from 3 weeks to 1 year of age. The main class was always binucleate 2c X 2, comprising approximately 80% of the entire population. Nor were many mononucleate tetraploids (4c) and octaploids of different types (8c, 4c X 2, 2c X 4, 2c + 2c + 4c) observed. An insignificant number of hexadecaploids (16c and 8c X 2) could be found in some animals. The mean protein content in myocytes was not always directly proportional to the weight of the ventricles. These data and a certain discrepancy between calculated wet and measured dry weights allowed us to assume that the water content and the non-muscle component of myocardium varied from heart to heart. In growing myocytes of different ploidy, the ratio of the myocyte masses did not correspond to the genome ratio 2: 4: 8: 16 being equal to 2: 3.3: 5.0: 6.3. Thus the growth of the cells outside mitotic cycle differs from that during polyploidization. PMID- 4032484 TI - Reperfusion injury induced by augumented oxygen uptake in the initial reperfusion period. Possible efficacy of extreme hemodilution. AB - This study was designed to investigate the relationship between myocardial oxygen consumption and oxygen-induced myocardial injury. Dog hearts were exposed to 40 min normothermic ischemia and then reperfused for 10 min with three oxygenated perfusates containing different hemoglobin concentrations and with moderate hemodilution. The experimental groups consist of a moderate hemodilution group (Group M) receiving 8 g/dl of hemoglobin, an extreme hemodilution group (Group E) given 4 g/dl of hemoglobin, and a hemoglobin-free autologous plasma group (Group F). Hearts in the non-ischemic control group (Group C) were also perfused with moderate hemodilution throughout. In Group C, Group M and Group E, the O2 tension of perfusates was maintained at about 100 mmHg and in Group F, at over 300 mmHg. Oxygen extraction at 5 min after reperfusion in Group C was 14%, in Group M and Group E less than 10%, but in Group F 70%. Oxygen consumption in Group F was more than twice that in Group E and surpassed that in Group C. Group M also showed a significant increase in oxygen consumption compared with Group E at 5 min after reperfusion. Among the ischemic groups, Group E showed improvement of left ventricular function almost comparable to Group C accompanied by a rapid decrease in myocardial lactate, improved preservation of myocardial adenine nucleotides and prevention of myocardial lipid peroxidation. In contrast, Group F showed persistently higher values of lipid peroxides and lactate, the poorest recovery of adenine nucleotides, and impairment of left ventricular function.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4032485 TI - Effects of nickel ions on the transmembrane action potential of guinea-pig heart preparations. AB - Experiments in isolated left auricle and right ventricular papillary muscle from guinea-pig hearts were performed in order to study the effects of nickel ions (Ni2+) on the transmembrane action potential. On the electrically paced guinea pig left auricle NiCl2 in 10(-8)M concentration did not modify the action potential (AP). 10(-7)M Ni2+ caused a slight hyperpolarizing effect, markedly enhanced the maximum rate of rise of AP (Vmax) and shortened the duration of AP.10(-6) and 10(-5)M NiCl2 dose-dependently accelerated the repolarization, while 10(-5)M had a strong depolarizing effect, too. The stimulatory effect of 10(-7)M NiCl2 on Vmax could be observed under Ca-free condition too. Increase of Vmax caused by 10(-7)M Ni2+ was not prevented by cholinergic blockade (atropine, 3 X 10(-7)M) by beta-adrenergic blockade (pindolol, 4 X 10(-7)M) or by inhibition of prostaglandin synthesis (indomethacin, 10(-6)M). On the electrically paced guinea-pig papillary muscle both 10(-7)M and 10(-5)M NiCl2 increased the resting membrane potential (RP), the overshoot and Vmax but accelerated only slightly the initial repolarization phase. A concentration of 10(-4)M NiCl2, however, without causing any effect on the other parameters, shortened the whole repolarization phase. The h infinity-curve relating Vmax of the ventricular action potential to the membrane potential was increased by 10(-7)M Ni2+. The increase of Vmax was more pronounced at membrane potentials more negative than -75 mV and could not be observed at membrane potentials more positive than -70 mV. Steady state inactivation of Vmax was shifted by 5 mV to more negative potentials by 10(-7)M Ni2+.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4032486 TI - Influence of genetic composition of test-animal populations on chronic toxicity studies used for risk estimation. AB - A lifespan exposure of mice to benzidine dihydrochloride was conducted for 33 m using both sexes of two populations of mice with the same gene pool. One population was the genetically homogeneous F1 hybrid produced by crossing BALB/cStCrlC3Hf/Nctr males with C57BL/6jfC3Hf/Nctr females. The second population consisted of genetically heterogenous monohybrid cross (MC) offspring produced by mating the F1 hybrids inter se. Data comparisons were made to determine if gene distribution among members of a population affects the response to a toxic insult. Endpoints tested consisted of mortality, liver tumor incidence and time of tumor onset, mortality from reticulum-cell sarcoma, and body weights. In most instances it was noted that among animals not dosed (controls), the F1 population had lower background incidence of lesions and lived longer than the MC population. However, among the dosed animals, the F1 mice were generally more susceptible to the toxic agent and developed higher incidences of the chemically induced lesions than did the MC population. The F1 hybrid population gave a more conservative estimate of risk than did the MC population. The calculation of the liver tumor risk for these two populations showed that lifespan exposure to benzidine would be predicted to result in a larger number (higher risk) when using the F1 data. A 4.5-fold difference in the toxic response was observed between the F1 females and the MC males. This emphasizes the importance of gene distribution in risk estimation studies. PMID- 4032487 TI - The human body burden of mirex in the southeastern United States. AB - Mirex is an organochlorine chemical with pesticidal and other industrial usages. Biologically, mirex was used as an insecticide for the control of imported fire ants in large areas of the southeastern United States. Evidence of mirex exposure in a national survey of chemicals in adipose tissue led to a more intensive survey of the general population in treated counties of the southeastern United States. Forty sites were selected randomly from 8 southeastern states where mirex was used widescale to combat fire ants; a total of 624 adipose tissue specimens were collected from these 40 sites. Tissue specimens were prepared by a modified Mills-Onley-Gather procedure and analyzed for mirex and selected other organochlorine compounds by electron-capture gas chromatography. Positive residue findings were confirmed by combined gas chromatography and mass spectrometry. Weighted statistical analysis of the data was conducted to estimate the level of mirex in the study area. It was estimated that 10.2% of the population of southern United States had quantifiable levels of mirex in adipose tissue. The estimated geometric mean of the quantifiable residue amounts was 0.286 ppm (lipid basis). Statistical tests of association and regression were used to investigate possible relationships between the presence and levels of mirex, and the Census Division or state of tissue-specimen collection, by age, race, and sex. These analyses indicated that region or location of tissue specimen collection (assumed to be area of residence) strongly related to both the presence of mirex residue and the amount of mirex residue detected. This may be correlated with the amount of mirex applied for fire ant control or with some other exposure patterns in different regions. PMID- 4032488 TI - Uptake and disposition of mirex in hepatocytes and subcellular fractions in CD1 mouse liver. AB - In vivo uptake and disposition of [14C]mirex by CD1 mouse liver subcellular fractions and cells of different nuclear ploidy were examined following single or multiple doses of mirex injected intraperitoneally. Significant amounts of mirex were rapidly taken up by liver (21-29%), suggesting that liver is one of the primary sites of accumulation of the chemical. Among subcellular fractions, mirex was predominantly distributed in mitochondria and microsomes in the irreversibly bound form (about 20%), although its levels fluctuated considerably with time. Mirex was completely dissociated with trichloroacetic acid treatment from both nuclear and plasma membrane fractions, although the total uptake by these fractions was markedly high. The time course of uptake and concentration dependent disposition of mirex revealed that polyploid hepatocytes selectively accumulated higher amounts of the chemical (two to three times) compared to diploid hepatocytes. The increased affinity of polyploid cells to mirex may indicate a greater susceptibility of this cell type to the chemical insult and also may suggest a possible early involvement of polyploids in the tumorigenic process in rodent livers. PMID- 4032489 TI - Dietary selenium, glutathione peroxidase activity, and toxicity of 2,3,7,8 tetrachloro-dibenzo-p-dioxin. AB - TCDD has been shown to inhibit selenium-dependent glutathione peroxidase activity. The role of selenium in TCDD toxicity is not known. We have therefore examined the effect of TCDD administration on hepatic glutathione peroxidase, aryl hydrocarbon hydroxylase, glutathione reductase, and glutathione S transferase activities, glutathione content, and lipid peroxidation in rats fed 0, 0.10, and 2.0 ppm dietary selenium. TCDD treatment significantly inhibited selenium-dependent glutathione peroxidase in animals on diets containing 0.10 and 2.0 ppm selenium. The selenium-dependent glutathione peroxidase activities in rats on 0.10 and 2.0 ppm dietary selenium were 8.3-and 4.7-fold greater than in animals fed a diet containing 0 ppm selenium. TCDD administration enhanced hepatic microsomal lipid peroxidation by factors of 4.0, 4.9, and 9.8 in animals fed diets containing 0, 0.10, and 2.0 ppm selenium, respectively. The administration of a lethal dose of TCDD to rats fed diets containing 0, 0.10, and 2.0 ppm selenium resulted in 0, 46, and 7% survival, respectively, after 66 d. Aryl hydrocarbon hydroxylase, glutathione S-transferase, and glutathione reductase activities were induced by TCDD. The results indicate that optimum dietary selenium provides partial protection from the toxic effects of TCDD. PMID- 4032491 TI - Toxicity of fenvalerate to developing steelhead trout following continuous or intermittent exposure. AB - Environmental toxicant exposure commonly vary in terms of duration and concentration. However, laboratory toxicity tests usually entail continuous exposures to constant concentrations. We compared survival, growth, and toxicant accumulation in early life-stage steelhead trout intermittently or continuously exposed to fenvalerate (FV) for 70 d after fertilization. Acute lethality was assessed in ancillary 96-h LC50 determinations with juvenile fish. Intermittent exposures were daily 4.5-h introductions of toxicant, and continuous exposures were to constant concentrations. All tests were conducted in a flow-through dilution apparatus, and mean concentrations for the entire exposure period were calculated for comparisons between regimens. The respective 96-h LC50 values for intermittently and continuously exposed were 88 and 172 ng/l. In the subchronic study, marked lethality (32%) and reduced terminal weight (50%) were found following exposures to cyclic FV concentrations that yielded an average of 80 ng/l (peak of 461). Continuous exposure to 80 ng FV/l did not affect these parameters. At mean FV concentrations above 20 ng/l, bioaccumulation was greater following intermittent than continuous exposure. Interaction of partitioning and elimination processes may partially explain differences in FV accumulation and subsequent toxicity. PMID- 4032490 TI - Hexachlorobenzene-induced porphyria in Japanese quail: changes in microsomal enzymes. AB - Hexachlorobenzene (HCB) was administered orally (500 mg/kg d) for 1, 2, 5, or 10d) to sexually mature Japanese quail to compare altered hepatic porphyrin levels with changes that occur in hepatic xenobiotic metabolizing enzymes. Porphyrin levels rapidly increased following the administration of HCB (three times control levels after a single dose of HCB), and birds began to develop porphyria (i.e., porphyrin levels were at least 10 times higher than controls) following 5 d of treatment. Following 10 d of HCB treatment, 3 of 4 treated quail were porphyric. Coincident with the HCB-induced disruption of the heme biosynthetic pathway were increases in various hepatic constituents. Changes included elevation of microsomal protein concentrations and increases in the specific content of cytochrome P-450, in the activities of aryl hydrocarbon hydroxylase (AHH), biphenyl hydroxylase (BPH), ethoxyresorufin-O-deethylase (EROD), and ethoxycoumarin-O-deethylase (ECOD), and in cytosolic and microsomal glutathione S-transferase (GSH-t) levels. In addition, the lambda max of the CO versus CO-reduced absorption spectra of hepatic microsomes from HCB-dosed birds showed a hypsochromic shift of 450 to 448 nm. The activity of NADPH-cytochrome P 450 reductase was increased following 10 d of HCB, and the activity of epoxide hydrolase was increased following 5 d of HCB. Most of these changes occurred with a single HCB treatment, and no further alterations developed in the nature of the response with repetitive dosing. Only weight loss, increased cytochrome P-450 content, and increases in GSH-t activity occurred simultaneously with the induction of porphyria. PMID- 4032492 TI - Developmental changes in the conversion rates of di(2-ethylhexyl) phthalate to monoethylhexyl phthalate in rats. AB - The activities of liver, lung, and kidney of rats of various age groups and that of placenta in hydrolyzing di(2-ethylhexyl) phthalate to mono(2-ethylhexyl) phthalate have been measured. Male and female rats of 45 d of age, neonatal rats within 12 h of parturition, and fetuses and placenta on d 19 of gestation were used. The liver was most active in all age groups; however, the lung and the kidney also had considerable activity. The tissues of the fetuses and the neonate had significant activity. The Km values of the enzyme were 4 mM in the neonatal liver and 5.9 mM in the adult liver. PMID- 4032493 TI - Effects of diethylhydroxylamine on hepatic microsomal lipid peroxidation and glutathione S-transferases. AB - The effects of diethylhydroxylamine (DEHA), a potent free-radical scavenger, on lipid peroxidation of rat liver microsomes were investigated in vitro. DEHA strongly inhibited ascorbate-dependent nonenzymatic microsomal lipid peroxidation. DEHA also completely inhibited nonenzymatic lipid peroxidation of heat-denatured microsomes, indicating that inhibition is protein-independent. DEHA only moderately inhibited NADPH-dependent enzymatic microsomal lipid peroxidation. DEHA has been shown to exhibit antitumorogenic properties. However, it had no significant effect on hepatic glutathione S-transferase, selenium independent glutathione peroxidase, or selenium-dependent glutathione peroxidase activity in the DEHA-treated CD-1 (lCR) Br male mouse. This suggests that the mode of action of DEHA as an antitumorogenic agent may be different from that of butylated hydroxyanisole, whose antitumor function is attributed to induction of glutathione S-transferase activity. PMID- 4032494 TI - Failure of exogenous prostaglandin to afford complete protection against acetaminophen-induced hepatotoxicity in the rat. AB - The protective effect of 16, 16-dimethylprostaglandin E2 (dm-PGE2) against acetaminophen-induced hepatotoxicity was determined in the rat. The dm-PGE2 was administered at two dose levels both before and after acetaminophen administration. The hepatotoxicity was evaluated by a rise in serum transaminases 24 h after acetaminophen administration and by histological examination of liver preparations. The urinary acetaminophen and its metabolites were determined by high-pressure liquid chromatography. The results suggest that exogenous dm-PGE2 administration had a modest protection against acetaminophen-induced hepatotoxicity, in contrast to its well established cytoprotective effect against many noxious agents in the gastrointestinal tract. Prostaglandin treatment had little effect on acetaminophen metabolites excretion in the urine, suggesting that it did not affect the cytochrome P-450-dependent mixed-function oxidase drug metabolizing enzyme system. The livers from dm-PGE2-acetaminophen-treated rats showed less advanced necrosis compared to those from saline-acetaminophen-treated rats. Whereas only 2 of 13 rats died in the prostaglandin-treated group, 4 of 13 rats died in the saline-treated group. PMID- 4032495 TI - Thyroid, bradycardic and hypothermic effects of perfluoro-n-decanoic acid in rats. AB - A single ip injection of perfluoro-n-decanoic acid (PFDA) to male Wistar rats resulted in an initially rapid, then gradual decrease in food consumption and a parallel loss of body weight. Body temperatures and resting heart rates were significantly depressed by PFDA treatment. As early as 12 h following a single dose of PFDA, serum thyroxine (T4) levels were significantly reduced and remained depressed throughout the 8 day study. Serum triiodothyronine (T3) was reduced by 35% 12 h following PFDA treatment and remained at that level throughout the study. These preliminary data suggest that an action on the thyroid axis may be an early primary response to PFDA and that some of the observed subsequent effects may in part be secondary to the change in thyroid hormone levels. PMID- 4032496 TI - Testicular changes in rats after administration of organotin complex. AB - Intratesticular administration of di-n-butyltin (o-hydroxyacetophenone S methyldithiocarbazate) has been shown to induce marked degenerative changes in the testes of adult rats. The possible mechanism of its action is discussed. In particular, an atrophy of seminiferous tubules with complete arrest of spermatogenesis has been noted. PMID- 4032497 TI - Observations on the distribution and movement of cadmium in epithelial cells of rat small intestine by light- and electron-microscope radioautography. AB - The localization of cadmium in the absorptive cells of the small intestine has been studied by light- and electron-microscope radioautography at intervals in the first 27 h after intubation of radiocadmium into the stomach of rats. Light microscope autoradiographic studies showed that cadmium was taken up very quickly by the absorptive cells, and radioactivity in the absorptive layer was disseminated over the entire area of the absorptive cells. Electron-microscope autoradiography showed that there was no concentration of radioactive cadmium in any particular site in the epithelial cells or in the lamina propria. It suggests that the transport mechanism of cadmium through the intestine may be nonspecific. Radioautographic investigation using radiocadmium may provide useful information for cadmium distribution and movement in rat small intestine. PMID- 4032499 TI - The genetic effects of the photochemical reaction products of propylene plus NO2 on cultured Chinese hamster cells exposed in vitro. AB - A study was made on the genetic effects of the photochemical reaction products of propylene plus NO2 on cultured Chinese hamster V79 cells with the use of sister chromatid exchanges (SCE). The photochemical reaction products of propylene plus NO2 were produced by photochemical reaction of a propylene-NO2/dry air system in a photochemical smog chamber and then were exposed to cell cultures for 2 h. SCEs were induced at all concentrations of the photochemical reaction products employed in the present study, the frequency of SCEs being two or three times higher than that of the controls. The genetic effects of NO2 and ozone (O3) were also studied and compared with those of the photochemical reaction products of propylene plus NO2. NO2 and O3 both induced SCEs in V79 cells, but their effects were weaker than those induced by the photochemical reaction products of propylene plus NO2. It was ascertained that the photochemical reaction of the propylene-NO2/dry air system produced much stronger genotoxic factors than the reactants. PMID- 4032498 TI - Reversibility effects on renal and hepatic gluconeogenic enzymes in rats from chronic exposure of cadmium. AB - The reversibility of cadmium chloride (CdCl2) effects on renal and hepatic gluconeogenic enzymes in rats was studied by removal of CdCl2 from the diet. Adult, male Sprague-Dawley rats were continuously treated with 0, 25, 50, and 75 ppm CdCl2 mixed in powdered diet for 180 d. After this period of chronic exposure, all treated rats were kept on CdCl2-free diet for another period of 180 d. The CdCl2 induced serum glucose and activities of glucose 6-phosphatase, fructose 1, 6-bisphosphatase, and phosphoenolpyruvate carboxykinase reversed to the levels of control values 120 d after the rats were fed with CdCl2-free diet. There were no significant differences in measured enzyme activities either 120 or 180 d after the cessation of CdCl2 treatment. The data indicate that CdCl2 effects on gluconeogenesis will gradually recover with time when the metal is removed from the diet. PMID- 4032500 TI - Lack of carcinogenicity of 8-nitroquinoline on long-term in vivo test in hamsters. AB - Syrian golden hamsters were administered 8-nitroquinoline, at a concentration of 0.05%, in a 10% ethanol solution as drinking water for 104 weeks. The animals were kept under observation until 112 weeks of age when the experiment was terminated. Both control and treated groups developed tumors in a pattern indistinguishable from that usually observed in Syrian golden hamsters. Thus the result of this experiment indicates that 8-nitroquinoline given orally at a concentration of 0.05% is not carcinogenic in Syrian golden hamsters. PMID- 4032501 TI - [Chronic toxicity study on difluprednate in dogs]. AB - The chronic toxicity of a new topical glucocorticoid, difluprednate (DFBA) was studied in Beagle dogs. DFBA ointment (0.05%) was percutaneously treated to the back of dogs at daily doses of 125, 12.5 and 1.25 micrograms/kg for 6 months. The local effects of DFBA In the treated area, thinning of the skin and inhibition of the fur-growth were observed with scale and erythema. The skin showed histological atrophy of the epidermis, a decrease of the adipose tissue and atrophy of the adnexa. These changes returned to normal after the 2-month withdrawal period. The systemic effects of DFBA In the 125 micrograms/kg group, the following changes were observed, although neither death nor severe symptoms occurred: General observations were seen an increase of water intake and urinary volume. A decrease of lymphocytes and eosinophils, and an increase of neutrophils were observed in the hematological examination. There were high sodium and low potassium levels, and an increase of alkaline phosphatase and gamma glutamyltranspeptidase activities in the biochemical examination. The organ weights showed a decrease of the thymus, adrenals, prostate and ovaries, and an increase of the liver and kidney. An atrophy of the lymphatic tissues and adrenal cortex, retardation of the sexual maturation, glycogen deposit in the hepatic cells, slight degeneration of the renal tubuli, and slight thinning of the sternum and non-treated skin were noted in the pathological examination. These changes returned to normal after the 2-month withdrawal period. In the 12.5 micrograms/kg group, the atrophic changes in the thymus, adrenal and non-treated skin appeared slight. In the 1.25 micrograms/kg group, no changes were found. Conclusively, all the local and systemic changes observed by DFBA in this study were due to the already known pharmacological effects of glucocorticoids. It is considered that a 12.5 micrograms/kg dosage is similar to a non-effect dose. PMID- 4032502 TI - Histological studies on developing chick embryos treated with aminoguanidine sulfate. AB - Fertile eggs were injected 10 or 20 mg/egg of aminoguanidine sulfate (AGS) into the albumen on the 5th day of incubation and examined macroscopically and histopathologically. The marked abnormalities were observed in liver, gallbladder and spleen while other organs were not different from the control. The earliest change was an increase of mitotic cells in the liver which reached to the peak at 2 days after the AGS injection. The increase of the ratio of cells in metaphase was characteristic. Decrease of weight, retardation of the development, fatty degeneration, necrosis and increase of connective tissues in the liver were followed. The abnormality of gallbladder such as aplasia and hypoplasia was observed with high frequency. Spleens of the AGS-treated group were enlarged from the 16th day of incubation. The clearest change of spleen was fatty degeneration. PMID- 4032503 TI - [Studies on antigenicity of difluprednate--antigenicity of difluprednate, phototoxicity and photocontact sensitivity of difluprednate ointment and cream]. AB - The antigenicity of difluprednate, phototoxicity and photocontact sensitivity of difluprednate ointment and cream were studied in guinea pigs and mice. The results in this study were as follows. Guinea pigs immunized with difluprednate emulsified with Freund's complete adjuvant did not exhibit the systemic anaphylaxis and the delayed type hypersensitivity by the elicitation with either difluprednate alone or difluprednate-BSA conjugate. The antisera obtained from these guinea pigs did not show the positive response in the homologous 4-hour PCA reaction and the passive hemagglutination test against the challenge of the same antigens described above. In the maximization test, guinea pigs immunized with difluprednate did not show the contact sensitivity when elicited with difluprednate suspended in saline. Guinea pigs applied difluprednate ointment did not show positive contact sensitivity by the elicitation with difluprednate ointment and ointment base. The antisera obtained from mice immunized with difluprednate and difluprednate-OVA conjugate absorbed to Al (OH)3 gel did not give the positive response in the 72-hour PCA reaction against the challenge of either difluprednte alone or difluprednate-BSA conjugate. In the phototoxicity and photocontact sensitivity test, 0.05% difluprednate ointment and 0.05% difluprednate cream did not show positive reactions in guinea pigs, although very slight erythema was caused by the primary irritancy of cream base, with or without irradiation of ultraviolet ray (320-400 nm). PMID- 4032504 TI - Penetrating neck trauma: diagnostic studies in the asymptomatic patient. AB - The selective management of penetrating neck trauma implies an attempt to individualize care and minimize unnecessary surgical exploration. In asymptomatic patients, diagnostic studies are performed in an attempt to exclude clinically unrecognized injuries. This review of 100 consecutive cases of penetrating neck trauma assesses the role of ancillary diagnostic studies in 53 patients selectively managed. The diagnostic yield from a combination of angiography, fluoro-esophagography, and aerodigestive tract endoscopy was 22.6% (12 of 53). However, only five patients (9.4%) actually benefitted from ancillary diagnostic studies, in that angiography documented clinically unrecognized injury. In an effort to avoid the indiscriminate use of ancillary diagnostic studies, a selective management plan based on anatomic zones of injury is provided. PMID- 4032505 TI - Hemipelvectomy, a lifesaving operation in severe open pelvic injury in childhood. AB - Near-complete traumatic hemipelvectomy probably carries an extremely high mortality rate. The usual techniques which have been used to control major hemorrhage associated with pelvic fractures such as transperitoneal vascular ligation, intra-arterial embolization, and packing are not applicable (14). Successful management requires prompt recognition of the nature of this injury so that surgical efforts may be directed at resuscitation and expeditious operative completion of the traumatic amputation. When this decision is made appropriately, the dual goals of control of hemorrhage and prevention of sepsis can be achieved. We report the management of a 7-year-old boy who sustained this injury after being struck by a tractor-trailer. In spite of massive resuscitation, hemorrhage could not be controlled and the child remained in shock. When it was recognized that he had sustained an incomplete traumatic left hemipelvectomy, it was surgically completed, permitting prompt control of the hemorrhage and restoration of hemodynamic stability. Intestinal and urinary diversion allowed an uneventful postoperative recovery without significant infection. Although hemipelvectomy appears to be a radical procedure in children with major pelvic injuries, it may be lifesaving and should therefore be considered in those with severe unilateral pelvic injury and uncontrollable hemorrhage. The potential for physical rehabilitation in the group of young, mostly male patients who have survived this injury appears to be unexpectedly good. PMID- 4032506 TI - Prehospital advanced trauma life support for critical penetrating wounds to the thorax and abdomen. AB - The role of advanced trauma life support (ATLS) in the prehospital care of the critically injured is highly controversial. This study analyzes the efficacy of ATLS in the management of critical penetrating wounds of the thorax and abdomen. In the 2 1/2-year period ending July 1984, 203 consecutive patients underwent emergency laparotomy or thoracotomy for gunshot and stab wounds. All patients were treated in the field by advanced paramedics (EMT-P). For gunshot wounds the mean time (+/- S.E.M.) responding to the scene was 4.5 (+/- 0.29) minutes, on the scene 10.1 (+/- 0.41) minutes, and returning to the hospital 6.4 (+/- 0.32) minutes. For stab wounds the mean time responding to the scene was 4.8 (+/- 0.21) minutes, on the scene 9.5 (+/- 0.37) minutes, and returning to the hospital 5.7 (+ 0.30) minutes. The number of intravenous lines started averaged 1.8 per patient. Eighty-one patients had PASG applied and 28 patients underwent endotracheal intubation (21 orally, seven nasally). Thirty-three patients had no obtainable blood pressure, of whom six survived (18%). One hundred sixty (94%) of the remaining 170 patients who had any initial blood pressure survived. One hundred nine (55%) patients had an increase in BP greater than or equal to 10 mm Hg (average, 35.6 mm Hg), 64 (32%) had no significant change, and 25 (13%) had a fall greater than or equal to 10 mm Hg (average, 24.2 mm Hg) from the field to the emergency department. Twenty (80%) of the 25 patients with a fall in blood pressure survived.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4032507 TI - Extrahepatic biliary tract injury: operative management plan. AB - Trauma to the extrahepatic biliary tract is rare but, if overlooked or improperly managed, may be associated with significant morbidity. The following is our most recent 6-year experience with this unusual injury. Among 949 patients undergoing laparotomy for acute trauma, there were 32 (3%) injuries to the gallbladder and five (0.5%) to the common bile duct. All patients with gallbladder injury underwent abdominal exploration because of associated trauma. Cholecystectomy was preferred for 24 (96%) of the 25 with penetrating wounds and three (43%) of the seven with blunt trauma. Nine (28%) patients developed postoperative complications but none were related to the biliary injury. All common bile duct injuries (CBD) were penetrating. Associated intra-abdominal trauma was always present. Partial lacerations were closed primarily over a T-tube. An intrapancreatic CBD lesion was managed by sphincteroplasty and stented with a T tube. The one patient with complete transection underwent choledochoenterostomy. Postoperative complications were common (50%) but none were related to the biliary injury. PMID- 4032508 TI - Long-term followup after traumatic asphyxia. AB - Victims of traumatic asphyxia syndrome were studied to determine: mechanism of injury, severity of injury, characteristic physical stigmata, treatment, and long term disability. Consecutive patients who sustained severe crush injuries with traumatic asphyxia in the 5-year period ending November 1984 were reviewed. Followup was established by personal examination or questionnaire. Severity of injury and disability were assessed by Injury Severity Score and questionnaire, respectively. Six patients, ranging in age from 4 to 65 years, were hospitalized from 4 to 150 days for traumatic asphyxia. The mechanism of injury in each case was severe crush by an object weighing greater than 1,000 pounds. All patients had associated injuries, often involving the thorax, and the mean Injury Severity Score was 14.5. Severe craniocervical cyanosis with petechiae was present in all patients. Four patients had temporary neurologic impairment. Despite severity of injury, no long-term disability was detected at an average followup of 4.4 years. No long-term survivors demonstrated residual cyanosis, petechiae, swelling, or neurologic sequelae. All had returned to work or school. PMID- 4032509 TI - Nephrectomy following trauma--impact on patient outcome. AB - Nephrectomy for trauma is done infrequently due to the success of renal sparing procedures. The purpose of this review was to quantitate the effect of nephrectomy on patient outcome. Over a 5-year period 55 of 783 patients had renal injuries confirmed at trauma laparotomy. Nephrectomy was performed in 14 (25%) of these patients. Thirteen patients had penetrating injuries (12 gunshot wounds, one stab wound) and one patient was the victim of blunt trauma. The average number of associated injuries was 3.6. Three patients exsanguinated intraoperatively. Renal failure (serum creatinine greater than 2.5 mg%) developed in four patients; three required hemodialysis. The average time of onset of renal dysfunction was 3 weeks, and in every case it was preceded by intra-abdominal sepsis. Two patients died, both from multiple organ failure, on postoperative day 25 and 26, respectively. In the seven patients free of renal failure, one patient developed sepsis and subsequently died. Of the eight surviving patients, all had adequate renal function as evidenced by an average blood urea nitrogen of 14 mg%, serum creatinine of 1.3 mg%, and a creatinine clearance of 77 ml/min. Renal failure following nephrectomy for trauma occurs late in the hospital course and is invariably preceded by sepsis. Nephrectomy is a marker of severe intra abdominal injury, but in itself is not the major determinant of survival. PMID- 4032510 TI - Skeletal muscle insulin unresponsiveness during chronic hyperdynamic sepsis in the dog. AB - Recent reports from our laboratory and others have documented changes in insulin unresponsiveness and electrolyte and hormonal changes characteristic of hypodynamic shock states in anesthetized animals. Since most acute shock protocols do not adequately mimic the clinical profile of sepsis, the present study was undertaken to document the hemodynamic and metabolic changes associated with chronic hyperdynamic peritonitis in dogs. Mongrel dogs of either sex weighing 20 +/- 2 kg were surgically instrumented with an electromagnetic aortic flow probe for monitoring cardiac output determinations, and aortic and central venous catheters for withdrawing blood for blood pressure and chemical analyses. Following a recovery period (7-10 days) control hemodynamic and metabolic measurements were made. Sepsis was induced (peritoneal abscess) by implanting a 4" X 4" gauze sponge, previously inoculated with human fecal bacteria, amid the intestines. Experimental (N = 18) and pair-fed control (N = 6) animals were monitored daily for 21 days or until death. During the septic protocol, cardiac index increased from a control value of 3.4 L/min/m2 to 5.5 L/min/m2 by the end of the experimental period. Mean arterial blood pressure, total peripheral resistance index, body weight, and plasma Ca++ fell below control values during the experimental period. Body temperature, plasma glucose, insulin, glucagon, and Mg++ were all elevated with sepsis. At the end of the chronic experimental period, skeletal muscle insulin responsiveness was assessed in the isolated, innervated, constantly perfused gracilis muscle preparation. Pair-fed control animals responded to various concentrations of local insulin infusion by increasing glucose uptake by the gracilis muscle. However, septic animals had a blunted response to local insulin infusion resulting in a decrease in the maximum dose response effect. These data demonstrate that: chronic, hyperdynamic peritonitis in the dog more closely mimics the human clinical profile of sepsis; and hyperdynamic sepsis is associated with a state of skeletal muscle insulin unresponsiveness which results from a post-receptor defect. PMID- 4032511 TI - Trauma myths and magic: 1984 Fitts lecture. PMID- 4032512 TI - Cimetidine therapy for burn shock: a quantitative assessment. AB - Optimal cardiac output (CO) resuscitation for severely burned guinea pigs is obtained with intravenous volumes of lactated Ringer's (LR) calculated at 4 cc/kg/%burn/24 hr. When one half this volume of LR is given (2 cc/kg/%burn/24 hr) CO is significantly (p less than 0.05) reduced at 2, 4, and 8 hours after injury. When early postburn cimetidine therapy (0.5 hours after injury) is added to only 1 cc/kg/%burn/24 hr LR, CO is significantly elevated for the same time periods and is not significantly different from CO values of LR at 4 cc/kg/%burn/24 hr for the first 24 hours after injury. However, postburn cimetidine therapy delayed until 1 hour after burn injury did not improve CO compared to treatment with LR at 2 cc/kg/%burn/24 hr. These observations suggest that early postburn cimetidine therapy administered within 1/2-hour of severe scald injury will result in significant CO improvement while simultaneously reducing resuscitative fluid volume requirements by as much as 70% for the first 24 hours after injury. PMID- 4032513 TI - The management of arterial injuries caused by penetration of zone III of the neck. AB - Penetrating trauma of the neck has been divided into three anatomic locations. Zone III, the subject of this paper, is defined as the area between the base of the skull and the lower border of the mandible. Management of these injuries remains problematic. Clinical assessment may be misleading, exploration may damage surrounding neurovascular structures, and injuries may go undetected. This has led us and others to advocate mandatory angiography before any surgical exploration. This report reviews 46 patients with Zone III injuries with respect to types of injuries, therapy and outcome. Angiography was normal in 22 patients who were treated conservatively with no complications. The remaining 24 patients sustained 39 arterial injuries diagnosed by contrast studies. Eighteen internal carotid injuries were identified in 16 patients. At operation ligation was performed in four patients and revascularization in two patients. One of the repairs subsequently thrombosed. Ten patients were managed nonoperatively by observation (seven patients) or angiographic embolization (three patients). Catheter embolization of the external carotid or its branches was performed to control bleeding (eight vessels) or close arteriovenous fistulas (two patients). Seven nonbleeding external vessels were successfully managed by observation. Two vertebral artery injuries were diagnosed. One required proximal embolization and distal ligation via occipital craniectomy to control a fistula between the vertebral artery and the jugular vein. Overall mortality was 8.6%. Three of the four deaths were in patients with neurologic deficit on admission. Another died of respiratory arrest. An air embolism resulting in hemiparesis was the only complication of the angiographic studies. We conclude that angiography is essential in Zone III neck wounds. It facilitates triage decisions and, combined with transcatheter embolization, enables the majority of these injuries to be managed without surgical exploration. PMID- 4032514 TI - Catheter aspiration for simple pneumothorax (CASP) in the outpatient management of simple traumatic pneumothorax. AB - Catheter aspiration for simple pneumothorax (CASP) was evaluated prospectively in the outpatient management of simple traumatic pneumothorax in 17 patients and compared to conventional tube thoracostomy (CTT) in 17 matched control patients. In 16 of the 17 consecutive study patients CASP maintained lung reexpansion without complications. Pneumothorax was due to needle puncture for drug abuse in 11 patients, stab wounds in five patients, and blunt trauma in one patient. The CASP patients were not hospitalized, whereas the control CTT patients averaged 4.9 days' hospitalization. CTT was associated with complications in two patients versus none for CASP. Parenteral analgesics were utilized for greater than 48 hours in CTT patients but were not needed for CASP patients. Costs averaged +310 for CASP compared to +3,030 for CTT. This ongoing pilot study data indicates that CASP is a reasonable alternative to CTT in selected patients with simple traumatic pneumothorax. PMID- 4032515 TI - The value of hepatobiliary scanning in complex liver trauma. AB - To evaluate the use of biliary scintigraphy with 99m Tc-dimethyl analogs (HIDA) in traumatic liver injuries, a group of 26 patients with penetrating and blunt liver injuries were studied. The results indicate that HIDA scanning is an effective noninvasive method of evaluating the hepatobiliary tree in the post traumatic setting. The HIDA scan is a sensitive tool for studying the hepatic parenchyma and the presence or absence of bile leaks. Its evaluation of the extrahepatic biliary ductal system is not specific and should be assessed with further studies. Gallbladder nonvisualization by HIDA scans in this setting cannot be presumed to be secondary to acute cholecystitis and should be interpreted with extreme caution. PMID- 4032516 TI - Renal pedicle injury in patients with multiple injuries. AB - In a study of 41 patients seen over 24 years, renal pedicle injuries were associated with life-threatening multiple system injuries and the immediate surgical management of these associated injuries by general surgeons took precedence over that of the renal pedicle injury. The result was the delayed diagnosis of the renal pedicle injury with loss of function of the kidney. In an effort to improve the renal salvage rate aggressive management of renal pedicle injuries with immediate radiologic evaluation and early surgical treatment was instituted in 1969. The records of 41 renal pedicle injuries from 1959 to 1983 were evaluated. Blunt external trauma was the cause in 76%. All 41 patients had multiple system injuries, averaging 3.7 associated injuries per patient, with 35 (85%) having a laparotomy for intra-abdominal injuries and an overall mortality rate of 44%. Conservative management was followed in 13 patients, with injury to the renal artery in nine and a branch of the renal artery in four, with a renal loss/delayed nephrectomy rate of nine of nine (100%) renal artery injuries. Immediate surgical management was performed in 23 patients, with injury to the renal artery in nine, the renal artery and renal vein in four, a branch of the renal artery in two, and the renal vein in eight, with a renal salvage rate of seven of 21 (33%) renal artery and/or vein injuries. Five patients died on admission or on the operating room table. A significant renal salvage rate resulted from immediate radiologic evaluation and early surgical treatment of renal artery/vein injuries compared to zero salvage rate with conservative management. PMID- 4032517 TI - Microsurgical replantation of the scalp. AB - Our 7-year experience with seven patients who had suffered avulsion of 30% or more of the scalp is reviewed. Six of the seven, who were candidates for microsurgical replantation, underwent successful replantation with 100% survival in five, and 50% survival in one. All had luxuriant regrowth of hair. The mechanisms of injury, emergency management, indications, and operative techniques are discussed. The role of interpositional vein grafts, and choice of vessels in contributing to this success is emphasized. The superiority of replantation over other methods of reconstruction of major scalp defects is demonstrated. PMID- 4032518 TI - Impalement injuries. AB - Impalement injuries are unusual, complex surgical problems. We present a case of impalement through the spine and abdomen, describe a two-team approach to operative extraction utilizing simultaneous laminectomy and laparotomy incisions, and outline the management of an infectious complication caused by unusual bacterial and fungal pathogens. General principles of management include: the impaling object must be stabilized and manipulation avoided during extrication and transport. Operative removal requires careful preplanning, and should be tailored to the specific presenting injuries, with early multispecialty involvement as necessary. Extensive exposure is mandatory and may be achieved through a variety of standard or unconventional incisions so as to permit extraction of the impaled object under direct vision. Meticulous care of the traumatic wound is necessary, and careful followup is required for recognition and early management of infectious complications. PMID- 4032519 TI - Evaluation of a health education programme in Tayba Qurashi Village, Central Sudan during 1983. AB - Schistosomiasis, diarrhoeal disease and malaria are spread by improper use of water. The influence of health education on the behaviour of women, who spend their time in the houses and are responsible for their children, was studied in regard to the use of water in Tayba Village in central Sudan. Seventy per cent of the women were illiterate. The education campaign improved understanding of how bilharzia is acquired and how to protect against it. Understanding of how diarrhoea occurs and how to prevent diarrhoea and malaria also increased. Progress was made towards keeping food correctly, in cleanliness of water jars and houses, and in disposal of garbage. The need for cleanliness of latrines and removal of stagnant water was emphasized. PMID- 4032520 TI - Control of schistosomiasis in the new Rahad Irrigation Scheme of Central Sudan. AB - As the new Rahad Irrigation Scheme in Central Sudan began its first agricultural season in 1978, the Blue Nile Health Project was being developed to prevent schistosomiasis and other water-associated diseases in the Rahad and Gezira Managil schemes. Taken as an indication of overall transmission in the Rahad scheme, the prevalence of infection among children in the newly established schools was found initially to be 14% for Schistosoma mansoni and 1% for Schistosoma haematobium in 1980. In the older Gezira-Managil irrigation system nearby, where transmission had not been controlled there was also little S. haematobium but the prevalence of S. mansoni in school-aged children was rising above 70%. To avoid a similar future in the Rahad scheme an integrated control strategy was implemented in 1980 using chemotherapy and snail control, supported by safe water supplies in every village. Under this strategy the prevalence of S. mansoni in the schoolchildren was reduced below 10% by 1983 at an annual cost of less than $4 per capita, about $300 per square kilometer. S. haematobium remained at 1% in the schoolchildren in 1983. The major cost was for village water supplies with about 20% of the total going for snail control and 10% or less for chemotherapy. Over a third of the cost was for equipment and supplies purchased abroad, requiring hard currency. Economically feasible prevention of transmission in the long-term will require reduction of the annual cost to about $1 per capita. Cost reductions should be made primarily in operation and maintenance of the water supply systems and in snail control. PMID- 4032521 TI - Protection of Sudanese irrigation workers from schistosome infections by a shift to earlier working hours. AB - Although schistosomiasis is an important occupational hazard for irrigation workers in Central Sudan, few measures have been found to protect them, short of abandoning the work. In an attempt to reduce their exposure to the large numbers of schistosome cercariae encountered in the water at midday, a group of Gezira canal cleaners were shifted to early morning working hours after being cured of their infections. They left the water each day at 10.00 hours, working from the canal banks thereafter. At the end of 6 months the prevalence of infections with Schistosoma mansoni was much lower in this group than in a similarly treated group with normal working schedules, indicating a practical way to protect irrigation and agricultural labourers. PMID- 4032522 TI - The lungfish Protopterus annectans (Owen) as a biocontrol agent against schistosome vector snails. AB - Laboratory and small-scale field experiments have been carried out to study the malacophagous capabilities of the lungfish Protopterus annectans. When individual fish were offered a range of aquatic fauna in aquaria in the laboratory only snails and dragonfly larvae were consumed. When offered a choice, the fish appeared to prefer snails, with larger individuals (up to 300 mm) capable of consuming up to 200 snails per day. The introduction of five P. annectans into a small concrete pond (diameter 5 m) with an established fauna and flora resulted in a reduction in the snail population of over 90% within 2 weeks. This reduction was maintained over a 4-month observation period suggesting that in habitats in which the lungfish can survive, there is a possibility of significant snail control. PMID- 4032523 TI - Survival, growth and reproduction of the imported ampullarid snail Marisa cornuarietis in Central Sudan. AB - The ampullarid snail Marisa cornuarietis was imported to the Sudan in 1981 for evaluation as a biological control agent against the planorbid snails which transmit human schistosomes. In initial field studies in small protected ponds the generation time of M. cornuarietis was 4 months, as in Puerto Rico. The snails reached 4 cm in diameter after 1 year, compared to 3 cm in Puerto Rico. Their population density varied from 60 to 175 snails per metre of shore-line, compared to a similar pond in Puerto Rico where the stable density was about 115 snails per metre. The proportion surviving after 1 year was 0.03, less than the annual proportion surviving of 0.10 in Puerto Rico. Thus the preliminary results indicated that the ampullarid snails could establish strong populations in permanent habitats in central Sudan where there was adequate food, although it might take longer than it does in Puerto Rico. PMID- 4032524 TI - Estimated risks and benefits from introducing Marisa cornuarietis into the Sudan. AB - As it has been proposed that Marisa cornuarietis, the ampullarid snail from the tropical Americas be used in the Sudan as a biological control agent against schistosomiasis, an estimate was made of the potential ecological hazards which might result from its widespread distribution in the Nile River Valley, and also of the potential benefits. The only foreseeable hazard would result from colonization of rice fields by the ampullarid snail and subsequent crop damage. However calculations on population dynamics indicated that Marisa cornuarietis would not be able to establish significant populations in rice fields in the Nile Valley as the flooded periods are too short. Thus the expected benefits of schistosomiasis control far outweigh any expected risks, and the ampullarid should be used in expanded field trials in the Gezira Irrigated Area as a control method for schistosomiasis. PMID- 4032525 TI - Malaria control in the Gezira-Managil Irrigated Scheme of the Sudan. AB - The development of malaria control in the Gezira-Managil Irrigated Scheme of Central Sudan has gone through several phases. As a result of agricultural and irrigation practices in the Gezira, falciparum malaria transmission became perennial instead of seasonal and the mosquito vector developed resistance to several insecticides. Subsequent failure to maintain control led to serious epidemics after 1971. By 1975 malaria was again put under control through an annual round of house spraying with malathion from 1975 to 1980, and with fenitrothion since 1981. A proposal is outlined for a rational strategy for malaria control in the future. PMID- 4032526 TI - The impact of the exotic fish Gambusia affinis (Baird and Girard) on some natural predators of immature mosquitoes. AB - The effects of Gambusia affinis on some suspected predators of mosquitoes were studied for a period of 12 months. A list of such predators was given. The most abundant invertebrate predators were Odonata, followed by Hemiptera and Ephemeroptera and the least common were Coleoptera. The population density of mosquito predators, with exception of Notonectidae and the fish Oreochromis niloticus, was markedly reduced in the presence of G. affinis. Application of aerial pesticides reduced the population of both G. affinis and O. niloticus fish. However it had no effect on the numbers of all invertebrate predators. PMID- 4032527 TI - The Blue Nile Health Project. A comprehensive approach to the prevention and control of water-associated diseases in irrigated schemes of the Sudan. PMID- 4032528 TI - Health, disease and water resources development. PMID- 4032529 TI - The Blue Nile Health Project: a comprehensive approach to the prevention and control of water-associated diseases in irrigated schemes of the Sudan. AB - This is a general report on the Blue Nile Health Project in the Sudan. The project was initiated in 1979 to develop better strategies for controlling the major water-associated diseases in tropical irrigation schemes. The 10-year programme will cost about $154 million (1978 prices). The Gezira, Managil and Rahad irrigation systems, all irrigated from the Blue Nile River, were selected for the project area as typical of irrigation systems throughout Africa and the Middle East where malaria, diarrhoeal diseases and schistosomiasis are endemic, and as the areas most urgently in need of disease control in the Sudan. The methods used for control of the water-associated diseases emphasize permanent improvements in water supply and sanitation, in environmental and agricultural practices, in health education, community participation and primary health services, and a reduction in dependence on pesticides and drugs. PMID- 4032530 TI - Focality and seasonality of Schistosoma mansoni transmission in the Gezira Irrigated Area, Sudan. AB - In the Gezira Irrigated Area of Central Sudan, transmission of Schistosoma mansoni was shown to be geographically focal, being concentrated near villages and small settlements. In a study during 1981 and 1982 of the entire area around a typical Gezira village almost 90% of the Biomphalaria pfeifferi snails carrying schistosome infections were found in one minor canal near the village. Sites near smaller settlements some distance from the minor canals yielded few infected snails. The factors which influenced the prevalence of infection in the snails were temperature, turbidity and human contact with the snail habitat. A strategy was proposed for control of Schistosoma transmission through focal and seasonal mollusciciding, health education, chemotherapy, improved water supply and latrine distribution. PMID- 4032532 TI - Snails and aquatic vegetation in Gezira irrigation canals. AB - All 38 minor canals in a limited area of the Gezira Irrigated Area were surveyed four times over a 2-year period to determine the aquatic and semi-aquatic vegetation types found and their distribution. A more detailed 2-year study of the correlation between snail density and aquatic vegetation was carried out in 18 of these canals. A total of 22 different species of weed were recorded, with floating and submerged weeds being more widespread and dense in the clear, slow moving water at the end of the irrigation season in March/April, than in the turbid flood waters in October. The schistosome vector snails Biomphalaria pfeifferi and Bulinus truncatus were found in conjunction with aquatic weeds and B. pfeifferi in particular increased in numbers as weed growth continued. In the second season of the study when mechanical weed clearing and regular focal mollusciciding was being carried out there was a noticeable reduction in weed density but repopulation was rapid. Snail numbers were reduced by mollusciciding and/or weed clearance in four canals, but outside the focal target canal stretches the weed clearance alone did not substantially reduce the snail populations. PMID- 4032531 TI - Transmission of Schistosoma haematobium in North Gezira, Sudan. AB - During this 14-month study, 128 765 Bulinus truncatus snails were collected from canals located near four villages in the northern part of the Gezira Irrigated Area, and were examined for patent trematode infections, by exposure to light. In all, 903 shedded cercariae, of which 424 were identified as S. haematobium, and one village, Bashagra, was the source of 80% of these S. haematobium infections. The highest density of snails occurred from March to May and the peak of snail infections occurred from June through August. The residents of the four villages and any adjacent small camps were examined for infection with S. mansoni and/or S. haematobium by collecting and examining stool and urine samples. The overall prevalences were 50% for S. mansoni and 20% for S. haematobium. The age prevalence curves were very different, with the prevalence of S. haematobium falling off more sharply in the over-20 age groups than was the case with S. mansoni. Observations at the human water contact sites suggested that the transmission of S. haematobium was increased when the canals contained shallow stagnant water, when the temperature was above 26 degrees C, and when the site was frequented by small children (particularly boys aged 5-15), for swimming. Our data suggest that at any site the transmission period is short and seasonal. PMID- 4032533 TI - Domestic and wild animals naturally infected with Schistosoma mansoni in the Gezira Irrigated Scheme, Sudan. AB - Domestic and wild animals were examined for natural infection with human schistosomiasis in Northern Gezira, Sudan. Postmortem examination of animals in a number of slaughterhouses revealed no infections in either sheep or goats but Schistosoma mansoni worms were found in two of the 98 cattle examined. Nile rats (Arvicanthus niloticus) were trapped and stray dogs were shot and examined for evidence of schistosome infection. The infection rate in Nile rats was 4.9% (8/164) and in dogs 27.3% (15/55) but whereas viable eggs were found in the excreta and tissues of the rats no eggs could be found in dog faeces. In the laboratory nine puppies were each exposed to 10 000 cercariae but there was no evidence that the infection had taken. It is concluded that A. niloticus, present in large numbers and often found in or near the canals, may be involved in S. mansoni transmission and could act as reservoir hosts, but that dogs are probably infected only in exceptional situations and are unlikely to play a major role in S. mansoni transmission. PMID- 4032534 TI - Schistosoma mansoni (Gezira) infection in Biomphalaria pfeifferi snails from Gezira and Jebel Marra. AB - The comparative susceptibility of Biomphalaria snails from Gezira and Jebel Marra to S. mansoni (Gezira) was investigated. Groups of laboratory-bred snails from the two localities were exposed to 0, 1, 2, 3 and 4 miracidia. The growth rate of the snails was followed over the experimental period by measuring the snails' shell size. Sub-groups of infected snails were examined for daughter sporocyst counts by crushing of the snails. Other groups of exposed snails were maintained until cercariae were shed. The exposed snails grew faster than the controls and growth was not dependent on the number of infecting miracidia. Jebel Marra snails grew faster than the Gezira snails and development of the daughter sporocysts within the snails was temperature dependent. Daughter sporocysts were first found on day 19 after exposure when the laboratory temperature ranged between 18 and 25 degrees C and on day 10 at a range of between 28 and 30 degrees C. Daughter sporocysts and cercarial counts overlapped in numbers per snail exposed to 1, 2, 3 and 4 miracidia for both Gezira and Jebel Marra snails. Nine out of 78 Jebel Marra snails were negative for daughter sporocysts, while all of the Gezira snails were positive. This might indicate greater susceptibility of the Jebel Marra snails to the parasite. Our experiments showed that snails from Jebel Marra are capable of supporting an S. mansoni infection from the Gezira until cercariae are shed. The epidemiological significance of the migrant labourers to the Gezira area in the transmission and spread of intestinal schistosomiasis in Jebel Marra is discussed. PMID- 4032535 TI - Influenza C virus RNA 7 codes for a nonstructural protein. AB - The complete nucleotide sequence of RNA segment 7 of influenza C/California/78 virus was determined by using cloned cDNA derived from viral RNA. The gene is 934 nucleotides long and possesses a long open reading frame which can code for a protein of 286 amino acids. Hybrid arrest translation experiments with the cloned cDNA fragment and poly(A)-containing RNA isolated from virus-infected cells showed that a 28,500-molecular-weight protein is coded for by RNA 7. Comparison of the proteins induced in the cell-free system and in virus-infected cells with those found in purified virus suggests that the 28,500-molecular-weight protein is a nonstructural protein. PMID- 4032536 TI - Expression of Sindbis virus structural proteins via recombinant vaccinia virus: synthesis, processing, and incorporation into mature Sindbis virions. AB - We have obtained a vaccinia virus recombinant which contains a complete cDNA copy of the 26S RNA of Sindbis virus within the thymidine kinase gene of the vaccinia virus genome. This recombinant constitutively transcribed the Sindbis sequences throughout the infectious cycle, reflecting the dual early-late vaccinia promoter used in this construction. The Sindbis-derived transcripts were translationally active, giving rise to both precursor and mature structural proteins of Sindbis virus, including the capsid protein (C), the precursor of glycoprotein E2 (PE2), and the two mature envelope glycoproteins (E1 and E2). These are the same products translated from the 26S mRNA during Sindbis infection, and thus these proteins were apparently cleaved, glycosylated, and transported in a manner analogous to that seen during authentic Sindbis infections. By using epitope specific antibodies, it was possible to demonstrate that recombinant-derived proteins were incorporated into Sindbis virions during coinfections with monoclonal antibody-resistant Sindbis variants. These results suggest that all the information necessary to specify the proper biogenesis of Sindbis virus structural proteins resides within the 26S sequences and that vaccinia may provide an appropriate system for using DNA molecular genetic manipulations to unravel a variety of questions pertinent to RNA virus replication. PMID- 4032537 TI - Adenovirus early region 4 encodes functions required for efficient DNA replication, late gene expression, and host cell shutoff. AB - To delineate the function of adenovirus early region 4 (E4) gene products, we constructed a set of mutant viruses which carry defined lesions within this coding region. Deletion and insertion mutations within six of seven known E4 coding regions had no measurable effect on virus growth in cultured cells. A variant carrying a deletion within the last coding region (encoding a 34,000 molecular-weight polypeptide) was modestly defective, and a mutant lacking the majority of the E4 region was severely defective for growth. The phenotypes of the two defective mutants are similar and complex. Both display perturbations in DNA replication, translation of the E2A mRNA, accumulation of late viral mRNAs, and host cell shutoff. PMID- 4032538 TI - Genetic mapping of endogenous RD-114 retroviral sequences of domestic cats. AB - The RD-114 family of endogenous retroviral sequences in domestic cats has been shown to consist of approximately 20 copies of genetically divergent virogenes per haploid genome. The chromosomal localization for four endogenous sequences (RDV1-4) was accomplished by correlating the occurrence of specific feline chromosomes with diagnostic viral DNA fragments in a panel of cat X rodent somatic cell hybrids. Analysis of the hybrid panel revealed that endogenous RD 114 sequences are dispersed on multiple cat chromosomes, that certain proviral segments are polymorphic with respect to the presence or absence of virus, and that a restriction fragment characteristic of inducible RD-114 resides on a single feline chromosome (B3), probably at a single locus. PMID- 4032539 TI - Validation of the tumor, nodes and metastasis classification of renal cell carcinoma. AB - A retrospective analysis of 252 patients with renal cell carcinoma was performed with the tumor, nodes and metastasis system of cancer staging. Each patient received a clinical and a pathological classification. Patient survival was calculated for each pT stage. All patients with stage pT1 disease (100 per cent) were alive at 5 years, as were 91 per cent of those with stage pT2 tumors. Higher T stages showed poorer survival; 58 per cent of the patients with stage pT3 and only 25 per cent with stage pT4 tumors were alive at 5 years. Invasion into the inferior vena cava (pT3c) had an adverse effect on survival, which was statistically significant compared to patients in the pT3a and pT3b subgroups. The type of surgical procedure performed had no influence on ultimate survival, nor did the use of adjuvant radiation therapy. The tumor, nodes and metastasis system clearly documents that the survival of patients with renal cell carcinoma depends on the local extent of the primary tumor, determined at the time of surgical exploration. PMID- 4032540 TI - Sexual function and female radical cystectomy: a case series. AB - We interviewed 9 sexually active women about sexual function before and after radical cystectomy. Of the women 6 also had received preoperative irradiation. Seven women resumed sexual activity. All subjects experienced dyspareunia on initial attempts but 6 had overcome the pain at followup 6 to 37 months postoperatively. These women were coitally orgasmic and reported no decrease in pleasure or change in the type of sexual stimulation required to produce orgasm. The results provide knowledge about the physiology of female orgasm and a basis for counseling patients. PMID- 4032541 TI - The management of strictures of the membranous urethra. AB - We present 40 cases of posterior urethral stricture resulting from pelvic fracture injury or prostatectomy. The strictures were managed according to various factors but most important were stricture length and the absence of pathological conditions in the anterior urethra. Post-traumatic obliterative strictures less than 2 cm. long can be managed with excellent success via a 1 stage perineal bulboprostatic anastomotic repair. Combined abdominoperineal procedures are equally successful but are reserved for patients in whom the stricture is more than 2 cm. long or who have an associated bladder neck pathological condition. When associated anterior urethral disease mitigates against mobilization and extension of the urethra to accomplish an anastomotic repair, the vascularized island flap or 2-stage scrotal inlay procedure appears to be the optimal choice. Of 3 failures with full thickness skin grafts 2 may have been owing to suboptimal graft beds in the scarred pelvic floor and perineum. Direct vision urethrotomy is advocated for nonobliterative posttraumatic strictures, and the rationale for dilation rather than urethroplasty management of postprostatectomy strictures is presented. PMID- 4032542 TI - One-stage penile/preputial island flap urethroplasty for urethral stricture. AB - A 1-stage urethroplasty for urethral stricture with a vascularized island of distal penile or preputial skin, which is relatively hairless, is described. The results of 27 patients treated since August 1981 are reviewed. PMID- 4032543 TI - Management of urinary incontinence in women with the artificial urinary sphincter. AB - This study concerns 39 women who underwent implantation of the artificial urinary sphincter for severe, persistent urinary incontinence following surgical correction of the anatomical deformity. The cause of incontinence was poor or absent function of the urethral sphincteric mechanism. The success rate in this series with the artificial urinary sphincter was 92 per cent. The condition of the tissues in the cuff area is crucial for success of the procedure. Some technical considerations of the procedure are discussed. PMID- 4032544 TI - Testicular torsion: Nigerian experience. AB - The records of 80 patients at this institution diagnosed as having testicular torsion during a 5-year period were examined to establish the characteristics and peculiarities, if any, of the disease in Nigeria. There were 74 suitable cases. Similar symptoms and physical signs were identified in Nigeria as have occurred elsewhere. However, contrary to reports from Europe and America the majority (57 per cent) of the patients with testicular torsion in this study were 20 or more years old. Also, torsion occurred significantly more often (9 per cent) in men 30 or more years old than has been reported in other areas. Only 5 per cent of the patients were less than 10 years old. There is no ready explanation why testicular torsion becomes manifest during adulthood in Nigeria. The testes were explored in 73 cases. Of the testes 25 per cent could not be salvaged because of infarction with acute torsion. However, the immediate testicular salvage rate of 75 per cent does not necessarily ensure long-term normal exocrine and endocrine testicular function. PMID- 4032545 TI - A late post-vasectomy syndrome. AB - A group of 20 surgical specimens in 18 patients with a previously unappreciated syndrome of unremitting epididymal pain and induration 5 to 7 years after vasectomy was collected during a 2-year interval. These symptoms uniformly were unresponsive to conservative measures, including empiric antibiotics. Total unilateral or bilateral epididymectomy and partial vasectomy led to complete relief of symptoms, usually within 24 hours. Pathological examination of the specimens revealed features consistent with sequelae of long-standing obstruction. Recognition of this late post-vasectomy syndrome, which represents a major complication of vasectomy, might be expected to increase as cohorts of vasectomized individuals age. PMID- 4032546 TI - Endocrine therapy for bladder outlet obstruction from carcinoma of the prostate. AB - The optimum treatment of bladder outlet obstruction from prostatic cancer is controversial. Although transurethral resection of the prostate may provide immediate relief of the obstruction, there are attendant surgical and anesthetic risks, as well as accumulating clinical evidence to suggest that transurethral resection of the prostate may cause tumor dissemination and diminish patient survival. Orchiectomy, which can be performed safely with local anesthesia, provides definitive endocrine therapy and has been used at our institution in preference to transurethral resection to relieve bladder outlet obstruction from carcinoma of the prostate. There were 35 patients between 51 and 96 years old in urinary retention from carcinoma of the prostate. Patients were treated with orchiectomy and suprapubic or urethral catheter drainage, and subsequently were given voiding trials. If a patient failed to void satisfactorily within 60 days transurethral resection of the prostate was performed. Over-all, 24 of 35 patients (68.6 per cent) were relieved of bladder outlet obstruction by orchiectomy alone. Neither tumor stage nor grade correlated significantly with the response to orchiectomy. We conclude that transurethral resection of the prostate may be held in reserve for patients who do not respond to endocrine therapy or those who do not wish to risk sexual impotence. PMID- 4032547 TI - Urolithiasis and race: another viewpoint. AB - We describe 193 consecutive individuals with documented urolithiasis in a military population. In contrast to other reports, the prevalence of stone disease was nearly identical in white-and black patients. This unique black population refutes the concept that urinary calculi are rare in blacks. PMID- 4032548 TI - Matrix glycosaminoglycan in urinary stones. AB - At first, urinary stones were classified according to their inorganic components (apatite, struvite, calcium oxalate monohydrate, calcium oxalate dihydrate and uric acid). Then, matrix glycosaminoglycan was extracted from the stones in each group and was analyzed by 2-dimensional electrophoresis. There were differences in the glycosaminoglycan content of matrices among different groups of urinary stones. The principal matrix glycosaminoglycan content consisted of hyaluronic acid in apatite and struvite stones, heparan sulfate in calcium oxalate monohydrate and uric acid stones, and hyaluronic acid and heparan sulfate in calcium oxalate dihydrate stones. We conclude that hyaluronic acid and/or heparan sulfate has an important role in urinary stone formation. PMID- 4032549 TI - Short-term versus prolonged systemic antibiotic prophylaxis in patients treated with indwelling catheters. AB - Newly hospitalized patients with stroke treated by indwelling catheters were assigned randomly to 3 treatment groups. Group 1 (24 patients) received 3 gm. ampicillin intramuscularly in divided doses 1 hour before, at the time of and 6 hours after insertion of the catheter. Group 2 (28 patients) received daily 1 gm. ampicillin intramuscularly every 8 hours. Group 3 (26 patients) was not subjected to any antimicrobial prophylaxis. Within 1 week after catheter insertion significant bacteriuria developed in 12.5 per cent of the patients in group 1, 42.8 per cent in group 2 and 45.1 per cent in group 3. The difference in the incidence between group 1 and either group 2 or 3 was statistically significant (p less than 0.02 and p less than 0.01, respectively). The mean number of strains (plus or minus standard error of mean) isolated per case of bacteriuria in group 3 (1.25 plus or minus 0.18) was significantly lower (p less than 0.05) and antimicrobial resistant strains were fewer (4 of 15) than in group 2 (1.75 plus or minus 0.13 and 12 of 21, respectively). PMID- 4032550 TI - The new ALR long cystoresectoscope system. AB - A new long cystoresectoscope system recently has become available. This instrument has the distinct advantage of allowing cystoscopy and endoscopic surgery of the lower urinary tract in men with an unusually long urethra, or a semirigid or intracorporeal inflatable prosthesis. PMID- 4032551 TI - Long-term followup of renal function after spinal cord injury. AB - Effective renal plasma flow was measured in acute spinal cord injury patients for up to 10 years after injury to determine the extent of renal deterioration in these patients and to identify the factors associated with a loss of renal function. The over-all mean decrease in effective renal plasma flow for all patients as a whole was 4.5 ml. per year. Factors associated with a statistically significant reduction in effective renal plasma flow included age, gender, renal calculi, quadriplegia, and a history of chills and fever. Other factors examined but not found to be statistically significant included years since injury, presence of severe decubiti, bladder calculi, bacteriuria and extent of injury. This study suggests that renal function usually can be preserved in spinal cord injury patients if the treatable risk factors are managed properly. PMID- 4032552 TI - Cutaneous ureterostomy in children--long-term followup. AB - From 1963 to 1983, 45 children with benign disease underwent urinary diversion with cutaneous ureterostomy. Patient selection for cutaneous ureterostomy was predicted on the presence of at least 1 dilated ureter. Followup ranged from 4 months to 20 years, with a mean of 7.9 years. Of the patients 29 (64 per cent) had a minimum followup of 5 years and 18 (40 per cent) were followed for more than 10 years. Postoperative complications, results of followup excretory urography and the ultimate fate of these children were analyzed. The results demonstrate the usefulness of cutaneous ureterostomy as a permanent form of urinary diversion in selected children. PMID- 4032553 TI - Characteristics of the male genitalia in the newborn: penis. AB - During a 2-month period all male newborns were examined prospectively to determine the normal characteristics of the penis. Of the 274 neonates examined 3 were excluded because of hypospadias with chordee. The spontaneous direction of the shaft was in the midline in 76.8 per cent, to the left side in 15.5 per cent and to the right side in 7.7 per cent. Partial absence of the prepuce was observed in 10 per cent of the patients, while an unretractable foreskin was seen in 23.2 per cent. The mean meatal aperture was 2.6 plus or minus 0.8 mm. Deviation of the median raphe was present in 10 per cent of the newborns and was associated with deviation of the meatus in 2.2 per cent. Mild torsion of the penis was noted in 1.5 per cent, while isolated torsion of 90 degrees was seen in 0.7 per cent of the patients. Early diagnosis and followup of these newborns might be helpful in determining further treatment. PMID- 4032554 TI - Nephro-duodenal fistula: a complication of percutaneous nephrolithotomy. AB - We report a case of a nephro-duodenal fistula complicating percutaneous nephrolithotomy that was managed conservatively. The patient was discharged from the hospital 14 days postoperatively, free of stone and doing well. The etiology and treatment of this problem are discussed. PMID- 4032555 TI - Durable response of a carcinoma in situ of the renal pelvis to topical bacillus Calmette-Guerin. AB - The first long-term remission of high grade, flat carcinoma in situ of the renal pelvis treated with topical bacillus Calmette-Guerin is presented. PMID- 4032556 TI - Ureteral triplication, contralateral duplication and bilateral extravesical ectopic ureter. AB - A case of ureteral triplication associated with contralateral ureteral duplication and bilateral extravesical ectopic ureter is reported. The child presented with urinary incontinence. The incidence, classification and embryology of triplication are reviewed. PMID- 4032557 TI - Vesical endometriosis: a review and 2 case reports. AB - Vesical endometriosis is uncommon and can result in months or years of morbidity if undetected. We report 2 cases that demonstrate that increased awareness of this entity and expeditious use of appropriate diagnostic techniques can lead to earlier diagnosis and definitive treatment. PMID- 4032558 TI - Papillary adenocarcinoma in situ of bladder. AB - To the best of our knowledge papillary adenocarcinoma in situ of the bladder has not been reported previously. We describe a case of transitional cell carcinoma in situ of the bladder associated with papillary adenocarcinoma in situ. While it is believed that most nonurachal adenocarcinomas of the bladder originate within cystitis glandularis, such transition is difficult to document. We assume that severe dysplasia of a papillary adenomatous component adjacent to papillary adenocarcinoma in situ represents an intermediate morphological change between cystitis glandularis and adenocarcinoma. Electron microscopic evaluation of glandular epithelium indicates that it represents the process of aberrant differentiation rather than a metaplastic phenomenon. PMID- 4032559 TI - Mesenteric venous thrombosis associated with estrogen therapy for treatment of prostatic carcinoma. AB - We report 2 cases of mesenteric venous thrombosis in men taking estrogen for carcinoma of the prostate. The possible relationship between the estrogen therapy and mesenteric venous thromboses is stressed, as well as the potential danger of resumption of estrogen therapy without anticoagulation postoperatively. PMID- 4032560 TI - Lumbosacral plexus stretch injury following the use of the modified lithotomy position. AB - The modified lithotomy position is used to provide simultaneous operative exposure to the abdomen and perineum. We report 3 lumbosacral plexus complications following use of this position. A mechanism involving stretch secondary to hyperabduction seems most likely. Electromyography is helpful in the diagnosis and the prognosis seems to be good. PMID- 4032561 TI - Bladder mucosal grafts: experiments with allografts in repairing bladder wall defects. AB - Free patch grafts of bladder mucosa and underlying lamina propria have been used to cover large defects in canine bladder walls. Both autografts and allografts were successfully transferred. Sex chromatin studies showed the final urothelial covering was from the recipient and not the donor bladder. PMID- 4032562 TI - The architecture of the musculature of the guinea-pig ureter as examined by scanning electron microscopy. AB - The muscular architecture of the guinea-pig ureter at different levels was examined by scanning electron microscopy. In the middle portion of the ureter, bundles of smooth muscle fibers were rather randomly oriented with respect to each other and to the long axis of the ureter, forming an irregular network. The muscle fibers of the upper ureter were mostly circularly oriented with a few outermost longitudinal muscle bundles. In the lower portion, the muscle bundles were predominantly longitudinally oriented overlying a deeper circular muscle layer. At any level examined, individual muscle fibers were about 100 to 150 microns. long and about 5 microns. wide, exhibiting a generally smooth surface. The adjacent muscle fibers were frequently interconnected by small lateral projections. In the pelvic portion, thin and short longitudinal muscle bundles were scattered over the inner circular muscles. Individual muscle fibers were spindle-shaped, about 70 microns. long, and 5 microns. wide at their thickest central portion. They were characterized by a rugged surface with many irregular projections and depressions. These muscle fibers may represent pacemaker cells. The findings were discussed in relation to the peristaltic movement of the ureter. PMID- 4032563 TI - Age-dependent aminoglycoside nephrotoxicity. AB - Urinary N-acetyl-beta-D-glucosaminidase activity was examined in 41 patients who received a 5-day course of aminoglycoside. Both pretreatment N-acetyl-beta-D glucosaminidase values and the increase in N-acetyl-beta-D-glucosaminidase after treatment were high in elderly groups, suggesting the increased vulnerability of the kidney with aging. PMID- 4032564 TI - Experimental cytoxan cystitis and prevention by acetylcysteine. AB - Cytoxan (cyclophosphamide) given to rats intraperitoneally produced a severe cystitis within four hours with marked inflammatory edema and hemorrhagic ulcerations of the mucosa. An in vivo staining test with methylene blue showed deep staining of the urothelium as has been demonstrated with other types of urothelial injuries; uninjured urothelium does not stain. The cytoxan cystitis is probably not due to cytoxan itself, but to a breakdown product acrolein, an aldehyde appearing in the urine. Rat experiments demonstrated that acrolein instilled intravesically produced a cystitis similar to that found with cytoxan injected intraperitoneally. The cystitis due either to cytoxan or acrolein was prevented by simultaneous intravesical administration of an aldehyde inactivating agent, acetylcysteine (mucomyst). PMID- 4032565 TI - A histological study of the urethra of the male baboon--is it similar to man's? AB - A comparative morphologic study of the male urethra was performed in 5 humans and 11 baboons. The corpus spongiosum is essentially the same in both humans and baboons, forming a definite organ with a lumen lined chiefly by a pseudo stratified columnar epithelium, a lamina propria, vascular space and smooth muscle, and an investing collagenous layer. Although present in the same anatomical areas there are fewer submucosal and periurethral glands in the baboon. PMID- 4032567 TI - Percutaneous removal of renal and ureteral calculi: experience with 400 cases. AB - Percutaneous removal of renal and ureteral calculi was performed in 500 patients since 1979. Experience with our first 100 cases enabled us to accumulate a variety of techniques. We report our experience with the subsequent 400 cases. As judged by plain films of the kidneys, ureters and bladder, and renal tomograms without contrast medium we attained a status free of stones in 99 per cent of the patients with renal and 94.5 per cent with ureteral calculi. Intravenous-assisted local anesthesia was used in 94 per cent of the cases. There was no mortality and the incidence of complications was low. Most patients with renal and ureteral calculi can be managed successfully and safely by percutaneous methods with good patient tolerance and minimal convalescence. PMID- 4032566 TI - The assessment of catheter-induced urethritis using an experimental dog model. AB - A new experimental model for the assessment of urethral catheters is described. Fifty catheters, comprising brands of latex, silicone, teflon-coated latex and polyvinylchloride (PVC) were assessed. The silicone, teflon-coated latex and PVC catheters were shown to cause minimal inflammatory change of the urethral mucosa, whereas the latex catheters showed variable and more marked changes. The model was simple to establish, and gave reproducible results. PMID- 4032568 TI - New self-draining basket loop for the treatment of ureteral stones. AB - A new ureteral loop is introduced that, in contrast to other loops, allows the kidney to be drained continuously during stone retrieval. Thus, complications caused by blockage of the ureter by the stone, such as fever and colic pain, are avoided. The basket shape of the loop provides optimum grasping of the ureteral stone. PMID- 4032569 TI - The ureteral folding technique for megaureter surgery. AB - The folding technique for megaureter surgery achieved a success rate of 94.6 per cent in 74 megaureters. In this series failure to correct reflux was noted in only 3 ureters and only 1 obstruction resulted. This operation theoretically preserves lower ureteral blood supply, eliminates suture line leakage and prolonged stenting, and is a model of cost-effectiveness. PMID- 4032570 TI - Full-dose irradiation for patients with invasive bladder carcinoma: clinical and histological factors prognostic of improved survival. AB - We reviewed the outcome of 55 patients treated from 1974 to 1982 by full-dose radiation therapy (6,400 to 6,800 rad) to identify factors associated with tumor radioresponsiveness and patient cure. All patients had histological proof of muscle invasion by tumor. Of the patients 8 (14 per cent) had clinical stage T2, 29 (53 per cent) stage T3 and 18 (33 per cent) stage T4 disease. Thirteen patients are alive, all but 2 without evidence of cancer. Survivors include 1 of 9 patients who underwent salvage cystectomy for a local recurrence. The actuarial 5-year survival rate for the entire group was 28 per cent, with a corrected survival of 33 per cent. Median survival was 2.3 years. Corrected survival for patients with stages T2 and T3 disease was 45 per cent versus 9 per cent for those with stage T4 cancer (p equals 0.009). Within the group with stages T2 and T3 cancer (all with proof of muscle invasion) the most striking prognostic factor was papillary surface histological findings, with local control by radiation therapy alone of 63 per cent versus 20 per cent in the group with solid or flat tumors (p equals 0.01), and corrected 5-year survival of 62 per cent (papillary) versus 0 per cent (flat or solid) (p equals 0.002). Other significant prognostic factors for 5-year survival in this group were extent of transurethral resection (54 per cent complete versus 17 per cent incomplete, p equals 0.009) and ureteral obstruction on excretory urography (47 per cent without versus 14 per cent with, p equals 0.01). Our results suggest that full-dose radiation therapy can be offered to patients with muscle-invading bladder cancer, with a relatively higher probability of success in those with less advanced tumors by clinical stage, papillary surface histological findings and no ureteral obstruction, and in whom a complete transurethral resection is possible. PMID- 4032571 TI - Radiation therapy for Peyronie's disease: is there a place? AB - Peyronie's disease is a disabling condition, the treatment of which remains controversial. We evaluated 40 patients who underwent external beam radiation therapy for the treatment of chronic Peyronie's disease. While patients with penile plaque, penile curvature and impotence were treated little improvement was noted. Patients with penile pain or pain on erection responded well to radiation with rapid resolution of the pain. We conclude that external beam radiation therapy has only limited application in patients with Peyronie's disease. Patients with primary symptoms of penile pain or pain with erection may be improved through the use of external beam radiation therapy. PMID- 4032572 TI - Isolation of Chlamydia trachomatis from the prostatic cells in patients affected by nonacute abacterial prostatitis. AB - To assess the presence of Chlamydia trachomatis in nonacute abacterial prostatitis 30 patients with urethral cultures positive for Chlamydia trachomatis underwent microbiological studies, including cultures of transrectal aspiration biopsies of the prostate. Chlamydia trachomatis was isolated from 10 of the prostatic specimens (33 per cent). In 3 cases a nonspecific cytopathogenic effect caused the destruction of the tissue cultures. Our findings demonstrate that Chlamydia trachomatis may cause ascending infections of the prostate and that this microorganism may have an etiological role in the pathogenesis of nonacute abacterial prostatitis. PMID- 4032573 TI - Holding postures characteristic of unstable bladder. AB - Holding postures to resist uninhibited detrusor contractions are illustrated and discussed. These postures were observed in children with urodynamically proved unstable bladders. The majority of the holding postures involved compressing the urethral meatus or the perineum in girls, or contracting all of the skeletal muscles or squeezing the glans penis in boys. The holding posture required the child to remain still. Younger children used straightforward holding postures, while older children adopted more sophisticated and less recognizable positions. These clinical observations seem to suggest that a physician should probably suspect an unstable bladder in any child who often demonstrates any of these postures. PMID- 4032574 TI - Preoperative prediction of continence after enterocystoplasty or undiversion in children with neurogenic bladder. AB - Fifteen children and young adults with neurogenic bladder undergoing enterocystoplasty were evaluated preoperatively to determine subsequent urinary continence and to establish the need for bladder neck reconstruction. The proximal sphincter mechanism was studied with an erect cystogram under fluoroscopic monitoring and the distal sphincter mechanism was studied with direct electromyography. In 8 patients the distal and proximal sphincters were incompetent, and all underwent a Young-Dees bladder neck reconstruction. In 7 patients 1 or both sphincters were competent and none underwent bladder neck reconstruction during enterocystoplasty. Of the 14 patients followed 13 are continent on intermittent catheterization. PMID- 4032575 TI - Noncompliant bladder resulting from posterior urethral valves. AB - We report on 4 boys with abnormally functioning, poorly compliant bladders and residual urine associated with posterior urethral valves. All 4 boys have been managed with clean intermittent self-catheterization and have shown stabilization or improvement in renal function, and improvement in upper tract drainage and urinary continence. The pathophysiological findings of this type of bladder dysfunction are discussed. PMID- 4032576 TI - Is Chlamydia trachomatis a cause of prostatitis? PMID- 4032577 TI - Elevated prostaglandin and indomethacin-responsive hypercalcemia in a patient with malignant pheochromocytoma. PMID- 4032578 TI - Congenital megacalices in a black woman. AB - Congenital megacalices is an uncommon anatomical malformation of the kidney. It has been reported previously only in white patients with a strong male predominance. We report congenital megacalices in a black woman. PMID- 4032579 TI - Pyocystis, pyonephrosis and perinephric abscess in end stage renal disease. AB - We report 8 patients with end stage renal disease on maintenance hemodialysis who had pyocystis, pyonephrosis or a perinephric abscess. Delay in diagnosis was frequent because the urine-deprived bladder and kidneys were dismissed as potential sites of infection. Treatment of pyocystis with bladder irrigations often was successful and obviated cystectomy. Pyonephrosis or perinephric abscess was a more serious problem and required unilateral nephrectomy. PMID- 4032580 TI - Peritoneal extravasation during percutaneous lithotripsy. AB - Extravasation of irrigation fluid during percutaneous nephrostolithotomy is a major complication and can result in severe morbidity. We report 3 cases of peritoneal extravasation of irrigation fluid. Ventilatory difficulty and narrowed pulse pressure suggest intraperitoneal extravasation of irrigation fluid, which should be treated by rapid drainage of extravasated fluid and careful monitoring of electrolyte concentrations. PMID- 4032581 TI - Intraoperative use of ureterorenoscope. AB - A new intraoperative use of the ureterorenoscope is described for open stone surgery. A mid ureteral stone that had moved back into the kidney was retrieved successfully through a ureterotomy incision, avoiding further procedures. PMID- 4032582 TI - Endoscopic transvesical ureterotomy. AB - Endoscopic transvesical ureterotomy was used in 2 cases of lower ureteral stricture. Ureteral catheterization was performed after dilation. Then, with cutting diathermy a Colling's knife was directed so that an incision was made at the 12 o'clock position, cutting onto the catheter and, thus, completing the ureterotomy. In each case the incision extended outside the bladder through the strictured segment of the ureter and above to the dilated ureter proximal to the stenosis. Obstruction was relieved in both cases and, although vesicoureteral reflux was present during voiding, excretory urography at 12 months demonstrated acceptable tracts. PMID- 4032583 TI - The management of civilian ureteral gunshot wounds: a review of 8 patients. AB - Ureteral injury is a rare consequence of abdominal gunshot wounds. We recently treated 8 patients with ureteral injuries. Failure to diagnose ureteral injury at presentation led to postoperative complications, necessitating additional operative procedures in 4 patients. However, in all 8 patients renal salvage was achieved. PMID- 4032584 TI - The use of bowel interposed between proximal and distal ureter in urinary tract reconstruction. AB - The replacement of lost ureter with bowel interposition is a feasible alternative in the reconstruction of the urinary tract. When adequate ureteral length is not present, interposition of a portion of small bowel between the proximal and distal ureteral segments is an option that minimizes the amount of bowel in the urinary tract. This, in turn, reduces mucus production and electrolyte absorption in the reconstructed urinary tract, and allows for more bowel to remain as part of the functioning gastrointestinal tract. This procedure allows use of the antirefluxing function of the normal ureterovesical junction when present. We have used successfully interposition of the small bowel between the proximal and distal ureteral segments for undiversion in 5 children. Generally, we strive to join urothelium to urothelium without the use of bowel in urinary tract reconstruction but when this is not feasible, bowel interposition has been a useful option. PMID- 4032585 TI - Nonrefluxing ureteroileal cystoplasty for bladder augmentation or replacement of ureters: long-term results of own technique. AB - The technique of a nonrefluxing end-to-end ureteroileal anastomosis is described. The conjoined ends of both ureters are formed into a 4 to 5 cm. long ureteral tube that is placed loosely into the bowel lumen. Increased intraluminal pressure during micturition closes the valve by compressing the ureter wall from outside, thus, preventing reflux. An end-to-end enteroureteral anastomosis has been used in 32 ileal or colon conduits and in 6 patients with ureteroileal cystoplasty. The followup (range 1 to 15 years) of these 6 patients who underwent bladder augmentation or ureteral replacement is presented. Based on this experience, this type of anastomosis appears to be fast and safe, without urine leakage, stenosis or reflux. The nonrefluxing safety valve mechanism makes this anastomosis applicable for bladder augmentation, with no ill-effects and good long-term function. PMID- 4032586 TI - Xanthogranulomatous cystitis. AB - Xanthogranulomatous lesions have been reported in many anatomical sites but only 10 cases involving the bladder have been described, 7 of which were associated with urachal adenoma. To our knowledge, we report the first instance of xanthogranulomatous cystitis in the English literature. PMID- 4032587 TI - Peritonitis and abdominal free air due to intraperitoneal bladder perforation associated with indwelling urethral catheter drainage. AB - Perforation of the bladder related to long-term indwelling Foley catheter drainage is a rare and serious complication. We report 2 cases of bladder perforation leading to generalized peritonitis and free intraperitoneal air. These cases re-emphasize the importance of considering bladder perforation in the differential diagnosis of the acute abdomen and of performing a complete abdominal exploration when the site of perforation is not easily detectable. PMID- 4032588 TI - Carcinoma of the male urethra. AB - Between February 1965 and November 1981 we treated 10 men with transitional or squamous cell carcinoma of the urethra. Treatment consisted of radiation therapy alone in 5 patients, operation alone in 4 and a combination of irradiation plus operation in 1. Radiation therapy produced local-regional control in 4 of the 5 patients with carcinoma of the distal or prostatic urethra, and 3 were completely free of disease at 5 years. The only complication of irradiation was urethral stricture in 3 patients, which was treated successfully by periodic urethral dilation. None of the patients treated by an operation alone or with irradiation achieved local-regional control. PMID- 4032589 TI - Primary mesonephric carcinoma of the female urethra. AB - We report the sixth case of mesonephric carcinoma of the female urethra, which is a rare urethral tumor arising from embryonal remnants of the wolffian or mesonephric duct. The 5 cases previously reported are reviewed. Despite the over all high stage and entire urethral location of these tumors at presentation, their innate biological malignant potential appears to be much less than the usual variants of urethral cancer. Radical surgical procedures appear to offer an excellent prognosis with a 5-year survival rate without evidence of recurrent disease approaching 80 per cent. PMID- 4032590 TI - Overflow urinary incontinence due to carbamazepine. AB - We describe the first well documented case of overflow urinary incontinence owing to prolonged carbamazepine treatment for temporal lobe seizures. Carbamazepine increased the bladder capacity to 1,700 ml. and was accompanied by symptoms of urgency and frequency. After carbamazepine was discontinued and the patient was given primidone the voiding symptoms disappeared. Post-voiding catheterization of the bladder showed minimal residual urine volume. In a review of urological adverse reactions of anticonvulsant drugs that are effective in the management of temporal lobe seizures we found that only primidone and phenobarbital have not been convincingly associated with such side effects. However, phenytoin and clonazepam have been linked with urinary incontinence, and valproic acid with enuresis. PMID- 4032591 TI - Genitoperineal injury induced by orthopedic fracture table. AB - Reduction and fixation of lower extremity fractures commonly involve use of the orthopedic fracture table, with incorporation of the perineal post for positioning and countertraction. Prolonged application of perineal pressure thereby is possible, with vulnerability to genitoperineal injury. Four examples are described. PMID- 4032592 TI - Spermatic cord arteriovenous fistula: an unusual complication of vasectomy. AB - A case of a large, symptomatic spermatic cord arteriovenous fistula following routine vasectomy is reported. This unusual complication required surgical intervention and has not been noted previously. PMID- 4032593 TI - Endometrial carcinoma of the prostatic utricle: a tumor of prostatic origin. AB - Endometrial carcinoma of the prostatic utricle previously was believed to be of mullerian origin. We report 2 cases studied by ultrastructural and immunoperoxidase techniques. Our results, as well as those presented by others, demonstrate the prostatic origin of this tumor. PMID- 4032594 TI - Chylous ascites complicating genitourinary oncological surgery. AB - Chylous ascites is an uncommon complication of retroperitoneal surgery. We report 2 cases of intraperitoneal chyle fistulas, one following retroperitoneal lymphadenectomy for testis cancer and the other after radical nephrectomy with regional lymphadenectomy for renal cell carcinoma. Both patients were treated successfully with medium chain triglyceride diets. We believe that most patients with chylous ascites will respond to simple dietary manipulation, and do not require complex and potentially morbid treatment regimens. PMID- 4032595 TI - Sequential studies of rat urinary bladder epithelial lesions induced by ifosfamide (Z4942). AB - Urinary bladder damage caused by ifosfamide in male F344 rats was studied by light microscopy and scanning electron microscopy. Ifosfamide was injected intraperitoneally at doses of 30, 60 and 120 mg. per kg. body weight, and rats were killed at several intervals following treatment. The changes in the epithelium observed by light microscopy and scanning electron microscopy following ifosfamide injection were compared to those observed following cyclophosphamide injection. Necrosis and exfoliation of the urinary bladder epithelium occurred after day 1 of ifosfamide treatment and were followed by regenerative hyperplasia. This hyperplasia was reversible. A dose response was evident in the number and size of lesions induced and the time of regeneration and repair. Scanning electron microscopy disclosed short, uniform microvilli on the luminal surface of cells during the early phases of hyperplasia. These microvilli persisted for only 1 day, from days 1 to 7, and days 1 to 12 respectively, following injection of 30, 60 and 120 mg. per kg. of ifosfamide. The hyperplastic lesions also contained cells with pleomorphic microvilli and ropy or leafy microridges on their surfaces. These findings after ifosfamide administration were similar to those reported to be induced in the urinary bladder by cyclophosphamide. PMID- 4032596 TI - Cancer serum index and prostatic acid phosphatase for detection of progressive prostatic cancer. AB - The ratio of alpha 1 acid glycoprotein/prealbumin, referred to as a cancer serum index, has been proposed as a marker for neoplastic disease. In a series of 130 patients with prostate cancer, the cancer serum index was measured along with serum prostatic acid phosphatase. A significant difference for both the cancer serum index and serum prostatic acid phosphatase was detected between those patients with no evidence of active disease after treatment and those with progressive disease after treatment. PMID- 4032597 TI - Urinary undiversion using the existing ileal loop and distal right ureter. AB - Urinary undiversion is an accepted technique in a highly selective patient population. We reconstructed the urinary tract in six female mongrel dogs. A 15 cm. segment of ileum was isolated, both ends were closed and bowel continuity re established. The proximal two-thirds of each ureter were anastomosed to the proximal end of the ileal segment. The distal one-third right ureteral segment, in continuity with the bladder, was anastomosed end-to-side to the distal ileal segment. Information from the intravenous pyelograms, renal function tests, electrolytes and pathological studies showed normal upper tracts without dilatation or obstruction, preservation of renal function and normal electrolytes except for mild hyperchloremia in all 6 animals. There was chronic pyelonephritis in one animal and mild focal renal inflammation in two animals. The uretero-ileal anastomoses were patent and the ureters were not dilated. The interposed ileum functions well as a conduit and does not become a reservoir over time. We believe incorporating ileum into the urinary tract in this technique of undiversion is a safe and effective clinical alternative in selected patients. PMID- 4032598 TI - Estimation by infrared spectrophotometer of the calcium oxalate dihydrate to calcium oxalate monohydrate ratio. AB - According to the theoretical expression for calibration curve as a function of the optical absorption ratio of two peaks and with the analysis of the infrared spectra of the mixture samples of commercial calcium oxalate monohydrate and synthesized calcium oxalate dihydrate, the following quadratic equation was obtained; Y = 1.79 X2 - 30.90 X + 107.04 in which Y is the percentage of the purity of calcium oxalate dihydrate and X is the ratio of the relative optical absorption at 660 cm.-1 (the wave number at a characteristic absorption peak of calcium oxalate monohydrate) to that at 610 cm.-1 (that of calcium oxalate dihydrate) by regarding the line as a base-line that links the absorption valley at around 700 cm.-1 with that at 550 cm.-1 The linear correlation coefficient of the actual purity to the estimated purity obtained from this formula of calcium oxalate dihydrate is 0.995. When this formula is applied to the results derived from the infrared spectra of the mixture samples of commercial calcium oxalate monohydrate and calcium oxalate dihydrate obtained from urinary stones in duplicate in each percentage, the linear correlation coefficient is 0.991. This estimation method by infrared spectrophotometer of the calcium oxalate dihydrate to calcium oxalate monohydrate ratio gave a very close correlation between actual and estimated purity of calcium oxalate dihydrate and seems useful in the study of calcium oxalate urolithiasis. PMID- 4032599 TI - Dynamics of the ureterovesical junction; a qualitative analysis of the ureterovesical pressure profile in the pig. AB - In pigs, ureterovesical pressure profiles were analyzed by combined prevesical perfusion pressure measurement and microsensor pressure profilometry of the ureterovesical junction, which showed comparable and reproducible fast and slow pressure waves. Cystoscopy revealed that the fast pressure waves were associated with fluid spurts from the ureteral orifice and wrinkling of bladder mucosa over the ureterovesical junction. During slow pressure waves only initial decreases in outflow from the orifice may occur. After dissection of the detrusor muscle at the UVJ only fast pressure waves were recorded. At similar pressure measurements on an inactivated ureter segment which was obliquely passed through the bladder wall only slow pressure waves could be detected. It is concluded that the fast pressure waves of the ureterovesical pressure profile represent peristaltic activity which is generated at the ureterovesical junction and by which fluid may be discharged into the bladder. The slow pressure waves of the pressure profile reflect impairment of flow through the ureterovesical junction by detrusor activity. PMID- 4032600 TI - Dynamics of the ureterovesical junction; effectiveness of its ureteral peristalsis in high pressure pig bladders. AB - In pigs, the effectiveness of ureteral peristaltic fluid discharge from the ureterovesical junction at high intravesical pressures was evaluated by ureterovesical perfusion pressure (UVPP) measurements and continuous endoscopic observation of the ureteral orifice during cystometry. Basal UVPPs either remained low, or were elevated but then intermittently could be reduced to near pre-bladder-filling levels at the end of the peristaltic pressure waves during which fluid was discharged from the ureteral orifice. Reductions of elevated basal UVPP correlated with the volumes of the associated discharged fluid boluses and with the perfusion times until such decreased basal UVPP again reached the elevated level it had before the peristaltic pressure waves. Even an elevated juxtavesical basal ureteral pressure which was already well below high intravesical pressure could be further reduced to near normal level after a ureteral peristaltic contraction which was accompanied by fluid discharge from the ureteral orifice. The clinical implications of these findings are discussed. PMID- 4032602 TI - 1984: Newspeak, doublethink, and vascular surgery. PMID- 4032601 TI - A genetically determined murine model of infantile polycystic kidney disease. AB - We have evaluated a congenic strain of mice with congenital polycystic kidney disease in which the disease process appears to closely resemble human infantile polycystic kidney disease. Cysts formed first in the proximal tubules of the nephron and appeared, by light microscopy, to be preceded by vacuolization of the cells. These spaces, as seen by electron microscopy, occurred between adjacent cells. The pancreas was severely involved with reduction of both exocrine and endocrine elements. Cyst formation in the liver was minimal. Serum samples evaluated for urea nitrogen and creatinine were significantly elevated in affected mice. Serum glucose was within normal limits. PMID- 4032603 TI - Idiopathic ischemic syndromes of the retina and optic nerve and their carotid origin. AB - Most eye problems referred to vascular surgeons for workup of carotid disease are either transient (amaurosis fugax) or partial (retinal branch artery occlusion) visual loss. Patients with more severe total infarcts of the retina (central retinal artery occlusion) or of the head of the optic nerve ("ischemic optic neuropathy") are seldom suspected of carotid disease and, in the latter case, are generally labeled idiopathic. An explanation for the difference in attitude towards these conditions is suggested. A prescribed carotid etiology for these various ischemic syndromes of the eye and optic nerve was explored in a study of 20 consecutive patients who had acute ischemic eye/optic nerve problems. Special visualization of the neck, orbital, and retinal vasculature was obtained. Sixty percent had ipsilateral and 50% had contralateral carotid artery disease. The ophthalmic artery and the posterior ciliary arteries showed intrinsic lesions each in 25% of cases. Our pilot study concludes that there is strong evidence that most of these ischemic eye syndromes are related to carotid artery disease, which is found in the majority of patients. In a minority of them ischemic problems may be due to arteritis or to intrinsic disease of the ophthalmic artery. A more cohesive approach to the study and treatment of these different entities is supported by the suggestion of a common etiology for most of them. Close collaboration with ophthalmologists will be needed to improve the present management of these eye conditions. PMID- 4032604 TI - Cumulative stroke and survival ten years after carotid endarterectomy. AB - With the life-table method, late stroke and survival data were calculated for 329 patients (mean age 59 years) followed a minimum of 10 years after carotid endarterectomy. The cumulative incidence of stroke was 24% at 10 years after operation, but only 10% of patients sustained strokes that clearly involved the ipsilateral cerebral hemisphere. Late strokes were most common (p less than or equal to 0.05) among hypertensive patients (31%), those with preoperative strokes (31%), and patients with recognized contralateral carotid stenosis (42%). Contralateral hemispheric strokes occurred in 36% of patients with uncorrected contralateral stenosis compared with 8% of those who had elective bilateral reconstruction (p = 0.09). Myocardial infarctions caused more late deaths (37%) than did strokes (15%), and 10-year survival after incidental myocardial revascularization (55%) was superior (p = 0.0001) to survival for patients with suspected but undocumented coronary disease (32%). PMID- 4032605 TI - Infrapopliteal bypass for established gangrene of the forefoot or toes. AB - This study was undertaken to assess factors affecting limb salvage after femorodistal bypass in patients with established gangrene. From January 1977 through June 1983, 361 patients underwent infrapopliteal bypasses; 58 patients (59 limbs) had forefoot and/or toe gangrene. There were 33 men and 25 women (mean age 67.6 years), and 40 patients (69%) were diabetic. A total of 71 femorodistal bypass procedures were performed in these patients: a single bypass in 49, repeat procedure in eight, and multiple bypasses in two patients. Graft material was autogenous saphenous vein in 22 cases, polytetrafluoroethylene (PTFE) in 39 cases, and a composite graft in 10 procedures. After bypass 50 patients underwent limited toe or forefoot amputation with uncomplicated healing. Limb salvage by life-table analysis was 70% at 1 year, 60% at 3 years, and 28% at 5 years. The graft patency at 3 years was 65% for vein grafts and 30% for PTFE grafts. In the entire series the operative mortality rate was 1.7%. Age, sex, hypertension, or diabetes mellitus did not influence the result of surgery. Similarly, failure of a previous femoropopliteal or tibial graft did not reduce the likelihood of limb salvage. Graft patency, however, is prerequisite for limb salvage, and graft patency can be maintained by thrombectomy or repetitive bypass. The present study suggests that limb salvage is possible in as many as two thirds of limbs with established gangrene. Although saphenous vein remains the graft material of choice, its absence should not preclude attempts at limb salvage. Repetitive grafting did not jeopardize patient safety but contributed significantly to extended limb survival. PMID- 4032607 TI - Balloon embolectomy catheters in small arteries: a technique to prevent excessive shear forces. AB - Balloon embolectomy catheters were studied in canine common carotid arteries (2 to 3 mm) in vitro to evaluate a technique of preventing excessive shear forces and to examine the effect of blood within the lumen. Each balloon was studied at 25, 75, 125, or 150 mm Hg lateral wall pressure. Shear forces were recorded in 16 vessels when the balloons were distended before catheter withdrawal, and these data were compared with forces recorded when the balloons were distended during catheter withdrawal. Results showed that distention of the balloon during withdrawal reduced shear forces 43.8% to 55.8% (p less than 0.05). In other experiments shear forces were recorded when the lumen was lubricated with heparinized saline solution, and these were compared with forces recorded when the lumen was lubricated with heparinized whole blood. The presence of blood in the lumen reduced shear forces 23.4% to 52.9% (p less than 0.05). From these studies it is recommended that during embolectomy in patients the balloons be distended during the first half centimeter or centimeter of catheter withdrawal to prevent excessive shear forces and that residual blood in the vessel lumen proximal to the point of embolic obstruction be accepted without concern, provided adequate heparinization has been achieved. PMID- 4032606 TI - Reproducibility of noninvasive tests of peripheral occlusive arterial disease. AB - We studied the reproducibility of four tests of peripheral occlusive arterial disease in 54 subjects, 32 of whom had this disease. We found that the reproducibility of systolic blood pressures obtained at rest from the thighs, calves, and ankles approximated that of arm systolic and diastolic blood pressures, as did the ankle-to-arm systolic blood pressure ratios. The average of the tenth and ninetieth percentile ranges of the resting systolic blood pressure ankle-to-arm ratios was +/- 0.10. Systolic blood pressures from the fingers were somewhat less reproducible, and those from the toes were even more variable. Systolic blood pressure ankle-to-arm ratios measured after the patient had exercised were less reproducible than resting ratios. The average of the tenth and ninetieth percentile ranges of the 1-, 3-, 5-, and 10-minute ratios after exercise was -0.13 to +0.16. Skin temperatures from the fingers and toes were approximately as reproducible as systolic blood pressures from the arms and legs and as the resting ankle-to-arm blood pressure ratios. Pulse-volume recordings from the thighs, calves, ankles, feet, toes, and fingers were very poorly reproducible. We conclude that information on the reproducibility of these measurements is essential in the evaluation of noninvasive arterial tests that are used to determine the course of peripheral occlusive arterial disease. PMID- 4032608 TI - A new method for the prediction of peripheral vascular resistance from the preoperative angiogram. AB - The preoperative angiogram is widely used to estimate runoff prior to infrainguinal bypass grafting, but the traditional method of angiographic scoring (0, 1, 2, or 3 based on the number of patent tibial vessels) correlates poorly with measurements of peripheral vascular resistance. We assigned a score of 0, 1, or 2 to each of four parameters (anterior and posterior tibial arteries [AT and PT], peroneal artery [PER], and plantar arch [ARCH]) on the preoperative angiograms of 39 patients admitted for elective femoral bypass grafting. These scores were then examined for their ability to correlate with the peripheral vascular resistance measured in each patient at the time of surgery. Multiple linear regression suggested that the scores assigned to the AT, PT, and ARCH were significantly correlated with observed resistance, but the PER subscore was not. Multiple linear regression of the AT, PT, and ARCH subscores suggested that resistance could be predicted from the equation: In (Resistance [mm Hg/ml/min]) = 0.786 - 0.268(AT) - 0.25(PT) - 0.358(ARCH), for which r = 0.78 and p less than 0.001. The ability of this relationship to predict resistance was tested by a division of the patient population into two roughly equal groups based on their observed resistance at surgery. When tested in this fashion, this equation had a sensitivity of 88% and a specificity of 82%. These findings suggest that the preoperative angiogram can be graded in a simple, yet unambiguous way, which allows a reasonable prediction of peripheral vascular resistance. PMID- 4032609 TI - External carotid revascularization: review of a ten-year experience. AB - In the presence of ipsilateral internal carotid artery (ICA) occlusion, external carotid artery (ECA) revascularization can improve cerebral perfusion or eliminate an embolic source. From 1974 through 1984, 37 patients at The Cleveland Clinic underwent 42 ECA reconstructions; autologous patch angioplasty and intraluminal shunting were used when feasible. Thirty procedures were limited to primary ECA revascularization, whereas 12 extended procedures were performed as reoperations after previous ECA endarterectomy or required complementary subclavian or intracranial bypass. There were no early postoperative deaths nor neurologic morbidity in the limited group, but one death, four ipsilateral hemispheric strokes, and one retinal embolism occurred in the extended group. Ten patients have died during a follow-up interval of 1 to 72 months (mean 27 months). Five late deaths were caused by myocardial infarction, only one of which was complicated by a contralateral stroke. Two additional strokes have occurred; one involved the ipsilateral and one the contralateral cerebral hemisphere. Five other patients experienced recurrent cerebral or ocular ischemic symptoms. In conclusion, extended ECA reconstruction is associated with a higher operative risk than limited revascularization. Late follow-up is necessary to detect those patients who may eventually require additional management of recurrent cerebrovascular symptoms or incidental coronary artery disease. PMID- 4032610 TI - The fate of human umbilical vein grafts as an infrarenal aortic substitute in monkeys. AB - The literature contains conflicting reports about the potential value of the processed human umbilical vein graft as an arterial substitute. With a view to a better understanding of the ultimate fate of this device, a series of long-term implantation was undertaken with a nonhuman primate model. Dardik Biografts were implanted as an infrarenal aortic substitute in 13 monkeys. Nine were put to death following complications after post-operative periods ranging from 3 months to 3 years, while four animals remain alive. No calcification or lipid infiltration was found, presumably because the animals were healthy. The patency rate was poor because of complications associated with thrombotic deposits and thinning of the graft wall after implantation, which led to stenosis and fibrous hyperplasia along the anastomoses. The external polyester mesh was found to encourage external tissue proliferation, which could not prevent the graft from dilating since it contained neither elastin nor smooth muscle cells. Because the places where the graft had been damaged before or during processing were the sites of thrombotic accumulation and initial collagen degeneration, it is essential to use only defect-free material. As a consequence the long-term durability of this graft continues to be questioned. PMID- 4032611 TI - Coexistence of abdominal aortic aneurysm and carcinoma of the colon: a dilemma. AB - The incidence of colonic cancer coexisting with an aneurysm of the abdominal aorta is approximately 2%. Such a coexistence presents a true dilemma to the surgeon for it is often difficult to decide whether to treat the carcinoma or the aneurysm first. This report summarizes the opinions of 46 Professors of General Surgery and Vascular Surgery who gave their response as to which condition should receive priority of treatment. Approximately one third of the respondents favored excision of the carcinoma first; one third stated they would excise the aneurysm first; and the remaining third said they would withhold a decision until laparotomy was performed. Two surgeons replied that they would attempt to perform aneurysmectomy and colectomy simultaneously. PMID- 4032612 TI - Endothelium develops on seeded human arterial prosthesis: a brief clinical note. AB - Despite a considerable and growing body of evidence that endothelial cell seeding accelerates the healing of arterial prostheses in laboratory animals, there has been no histologic evidence thus far to indicate that a similar process occurs in human beings. A case is reported of histologically confirmed, extensive endothelial healing on a polytetrafluoroethylene femoropopliteal bypass graft 90 days after it was seeded and implanted. PMID- 4032613 TI - Spontaneous dissection of the superior mesenteric artery. AB - A patient presented with chronic visceral ischemia caused by spontaneous dissection of the superior mesenteric artery; this was treated successfully by "intimectomy" and patch angioplasty. Operative rather than expectant management is recommended for this rare but surgically accessible lesion. PMID- 4032614 TI - Femorotibial vein bypass in a child. AB - This report details the course and management of a 5-year-old girl with intermittent claudication, a chronic leg ulcer, and discrepancy in leg growth caused by unilateral femoropopliteal arterial occlusive lesions of obscure etiology. Angiographic evaluation, pathologic observations, and surgical management of this child are detailed. A 4-year follow-up has provided gratifying results that justify the surgical approach to this unique patient. PMID- 4032615 TI - The superficial femoral artery as a conduit: an alternative to prosthetic material. AB - The occluded superficial femoral artery is almost universally present in atherosclerosis obliterans and requires vascular reconstruction. As an alternative autogenous conduit, when a suitable saphenous vein is not available, the properly prepared superficial femoral artery can obviate the need for prosthetic material. The technique for preparing the artery for use as a graft is discussed. A case of the superficial femoral artery used as an autogenous conduit is presented. PMID- 4032616 TI - Medial approach to the anterior tibial artery. PMID- 4032617 TI - The supraclavicular approach to scalenectomy and first rib resection: description of technique. PMID- 4032618 TI - Patency in canine inferior vena cava grafting: effects of graft material, size, and endothelial seeding. PMID- 4032619 TI - Arterial wall microbiology and graft infections. PMID- 4032620 TI - Experimental plague in rock squirrels, Spermophilus variegatus (Erxleben). AB - Experimental infections with Yersinia pestis were followed in groups of rock squirrels. Development of coagulopathy and pneumonia were observed in 2-4% and 11 12% of the test animals, respectively. Susceptibility to experimental infection was heterogeneous with some animals surviving inoculation with large numbers of organisms and others succumbing after inoculation with small numbers. Production and longevity of serum antibody titers, as measured by passive hemagglutination tests, were variable as well, and apparently unrelated to dose. The data presented attest to the need for care in interpreting serologic tests results for individual animals. PMID- 4032621 TI - Experimental transfer of Trichomonas gallinae (Rivolta, 1878) from white-winged doves to mourning doves. AB - Isolates of Trichomonas gallinae (Rivolta, 1878) from white-winged doves, Zenaida asiatica (L.), were transferred experimentally to young mourning doves, Zenaida macroura (L.). Twenty-three of 25 mourning doves developed infections with isolates of T. gallinae from 25 white-winged doves. In addition, eight of eight rock doves (Columba livia Gmelin) were infected with duplicate isolates. All infected recipient birds harbored avirulent isolates except for one mourning dove which died from extensive oral lesions. However, repeated attempts using this isolate of T. gallinae to produce lesions in additional recipients were unsuccessful. Despite the findings of this study, it was suggested that future dove management strategies consider the possibility of disease outbreaks involving white-winged doves and susceptible populations of mourning doves. PMID- 4032622 TI - Prevalence of helminths in a cyclic snowshoe hare population. AB - Five species of helminths were monitored in a population of snowshoe hares (Lepus americanus) near Rochester, Alberta, during 1961-1977. Prevalence of both Obeliscoides cuniculi and Protostrongylus boughtoni among young hares averaged about 50% by age 2 mo, then tended to level off. Prevalence of Taenia pisiformis (cysticerci) and Dirofilaria scapiceps rose more slowly, but continued to increase steadily beyond their mean levels of 8% and 1% at age 2 mo. There were well defined seasonal (within-year) cycles in prevalence of O. cuniculi and P. boughtoni that were generated evidently to a major degree by arrested development of larvae in fall and renewed development in late winter. It was hypothesized that renewed larval development was triggered (in February) in O. cuniculi by the seasonal rise of circulating pituitary gonadotrophins, and (in April) in P. boughtoni by the seasonal rise of gonadal androgens and estrogens. Indices to gonadal hormone levels in hares indicated that these increased most rapidly among males, and may have accounted for the higher prevalences of P. boughtoni in males during April-May. Neither T. pisiformis nor D. scapiceps exhibited conspicuous seasonal changes in prevalence. Maximum prevalence of T. pisiformis was attained at about 1 yr of age, whereas D. scapiceps increased among adult snowshoes through age 2 yr before stabilizing. Long-term (between-year) changes in prevalence of O. cuniculi, T. pisiformis, and D. scapiceps were correlated significantly with the cyclic hare population which declined from a peak in fall 1961 to a low in 1965-1966, rose to another peak by fall 1970, and declined again to a low in 1975. There was no detectable time lage between this "10-yr" cycle in hare density and the cycles of parasite prevalence among juveniles (less than 1 yr of age). Among adult hares, the cycle of O. cuniculi prevalence was likewise synchronous with that of the hare population, but the cycles of D. scapiceps and T. pisiformis lagged by approximately 1 and 2 yr, respectively. This lag in T. pisiformis prevalence was largely inexplicable to us. Our data on P. boughtoni were not suitable for analyses of between-year trends; nor were those for the fifth helminth, Taenia serialis (coenuri), because mean prevalence was less than 1% among both juveniles and adults. An apparent decline in T. serialis after the early 1950's, and its continued scarcity thereafter, paralleled a major change in numbers of one important definitive host--the red fox (Vulpes vulpes).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 4032623 TI - Factors affecting the helminth community structure of adult collared peccaries in southern Texas. AB - Four species of nematodes (Gongylonema pulchrum, Parabronema pecariae, Texicospirura turki, and Physocephalus sexalatus) and one species of cestode (Moniezia sp.) comprised the helminth fauna of adult collared peccaries (Tayassu tajacu) from the plains in southern Texas. The community structure of the helminth fauna of peccaries from this region was basically dissimilar to that from the more humid Gulf coastal prairies of southern Texas in composition (by the conspicuous absence of certain species) and relative abundance of shared species. The distributions of each of the three common species of helminths (G. pulchrum, T. turki, and P. sexalatus) were overdispersed. The effects of selected habitat variables operating across host subpopulations (delineated by condition and sex) and of the extrinsic variable of season on the dispersion patterns of the three common species of helminths were examined. The hypothesis that heterogeneity within the host population, rather than across the collective host population, is the main factor generating overdispersion in natural parasite populations was not confirmed for the three common species of helminths. Overdispersion in P. sexalatus resulted from seasonal changes across the collective host population, with the greatest abundances occurring during the cool season. Aggregated abundances of G. pulchrum resulted from variation generated across host sex subpopulations, while the dispersion patterns of T. turki appeared to be unaffected by the habitat variables examined in this study. PMID- 4032624 TI - Effects of season and physical condition on the gastrointestinal helminth community of white-tailed deer from the Texas Edwards Plateau. AB - Eighty-six adult female white-tailed deer, Odocoileus virginianus (Zimmermann), collected over a 12-mo period in the Texas Edwards Plateau, harbored six species of nematodes (Haemonchus contortus, Gongylonema pulchrum, Oesophagostomum venulosum, Ostertagia ostertagi, Cooperia sp., and Apteragia odocoilei), and two cestodes (Moniezia sp. and Taenia hydatigena). The patterns of distribution of the three common species of gastrointestinal helminths (H. contortus, O. venulosum, and G. pulchrum) were overdispersed. When analyzed for the main and interactive effects of the extrinsic and intrinsic variables of season and physical condition, respectively, aggregated abundances in H. contortus and O. venulosum appeared to result from the main effect of seasonal changes operating over the collective populations of these two species rather than from the intrinsic factor of physical condition operating within selected subpopulations. Abomasal parasite counts do not appear to be a useful index for monitoring herd condition of white-tailed deer from this geographic region. PMID- 4032625 TI - Factors affecting transmission of larval winter ticks, Dermacentor albipictus (Packard), to moose, Alces alces L., in Alberta, Canada. AB - The larval stage of the winter tick, Dermacentor albipictus, was studied under field conditions in central Alberta, Canada. Larvae ascended vegetation in autumn, possibly in response to photoperiod. Numbers found by flagging increased from early September to early October and decreased gradually to zero by December. Larvae clumped on the tips of vegetation approximately 1-1.5 m off the ground, and did not exhibit a diurnal, vertical migration. Activity was temperature dependent and no obvious preference of vegetation species for ascension was detected. Transmission of larvae to moose was probably facilitated by synchrony of the larval activity period with the moose breeding season in autumn. PMID- 4032626 TI - Effects of fluoride ingestion on white-tailed deer (Odocoileus virginianus). AB - The effects of the addition of 25 or 50 ppm fluoride (F), as sodium fluoride (NaF), to the rations of 5-mo-old male white-tailed deer were similar to those observed in domestic cattle fed similar amounts of fluoride. The ingestion of 50 ppm F for 2 yr resulted in the accumulation of over 7,000 ppm F in bone ash. Accumulation of fluoride in antlers was extensive and occurred more rapidly than in skeletal tissue. Fluoride ingestion resulted in lesions on the developing incisors that were similar, but not identical to those seen in other species. Increased molar wear in the deer fed 50 ppm F was minimal, and no gross pathology of the mandible was observed. Only mild hyperostosis of the long bones was evident. PMID- 4032627 TI - Heavy metals in white-tailed deer living near a zinc smelter in Pennsylvania. AB - White-tailed deer (Odocoileus virginianus (Zimmermann) shot within 20 km of the zinc smelters in the Palmerton, Pennsylvania area contained extremely high renal concentrations of cadmium (372 ppm dry weight (dw] and zinc (600 ppm dw). The deer with the highest renal zinc concentration was shot 4 km from the smelters and had joint lesions similar to those seen in zinc-poisoned horses from the same area. The highest concentrations of lead in both hard and soft tissues were relatively low, 10.9 ppm dw in a sample of teeth, 17.4 ppm dw in a metacarpus, and 4.9 ppm dw in a kidney. PMID- 4032628 TI - Rabies virus in salivary glands of raccoons (Procyon lotor). PMID- 4032629 TI - Mycotic pneumonia and meningoencephalitis due to Aspergillus terreus in a neonatal snow leopard (Panthera uncia). PMID- 4032631 TI - Experimental coccidiosis (Isospora suis) in a litter of feral piglets. PMID- 4032630 TI - Coccidioidomycosis (Coccidioides immitis) in the collared peccary (Tayassu tajacu: Tayassuidae) in Texas. PMID- 4032632 TI - Larval cestodes (Mesocestoides sp.) in the liver of the island night lizard, Xantusia riversiana. PMID- 4032633 TI - Leeches on freshwater farmed fishes in Iraq. PMID- 4032634 TI - An evaluation of burning for control of winter ticks, Dermacentor albipictus, in central Alberta. PMID- 4032635 TI - Parasitic arthropods of wood ducks, Aix sponsa L., in the Atlantic Flyway. PMID- 4032636 TI - Famphur toxicosis in a bald eagle. PMID- 4032637 TI - Thyroid adenoma and ovarian luteinization in an aged fisher (Martes pennanti). PMID- 4032638 TI - Papillomatous lesions in wild juvenile Atlantic salmon, Salmo salar L., in New Brunswick, Canada. PMID- 4032639 TI - Fatal trauma caused by a deterrent device for bears. PMID- 4032640 TI - Hemoglobin interference in the direct determination of erythrocyte protoporphyrin concentrations for monitoring lead intoxication of waterfowl. PMID- 4032641 TI - Ethical considerations in research on wildlife diseases. PMID- 4032642 TI - Risk assessment, management addressed at "Prevention 85". PMID- 4032643 TI - "Heart at Work" campaign encourages healthier living. PMID- 4032644 TI - Leads from the MMWR. Education and foster care of children infected with human T lymphotropic virus type III/lymphadenopathy-associated virus. PMID- 4032645 TI - Re: Efficacy of influenza vaccine. PMID- 4032646 TI - Labetalol for hypertension. PMID- 4032647 TI - Tolerance to oxprenolol. PMID- 4032648 TI - President's address. Weathering the storm. PMID- 4032649 TI - Progress in the surgical treatment of cardiac arrhythmias. Initial experience of 90 patients. AB - Between 1981 and 1985, ninety patients were treated surgically for cardiac arrhythmias and have been followed for a mean interval of 21 months (range, one to 49 months). Follow-up is 100% complete. Fifty accessory pathways were divided in 35 patients (25 male and ten female; mean age, 35.2 years; range, 10 to 72 years), with no deaths. Five females, aged 10 to 35 years, were treated for focal atrial tachycardia, three for an atrial focus alone, and two with other arrhythmia procedures; four were cured and one was improved. Two patients (one man and one woman, both aged 33 years) had ablation of the atrioventricular node. Forty-one patients (32 male and nine female; average age, 56.9 years; range, 15 to 74 years) had ablation of ventricular tachycardia. Kent bundle division and focal atrial tachycardia ablation were also performed in two of these patients. More than 80% of patients had coronary disease. Mean preoperative ejection fraction was 33.9% with a range of 14% to 65%. Aneurysmectomy, endocardial resection, cryoablation, and coronary artery bypass were the procedures used. The perioperative mortality rate was 9.8% but there were no deaths in the last 23 patients. Ventricular tachycardia was abolished in all but three survivors in whom medical treatment is now effective. The automatic implantable defibrillator was implanted in 11 patients, with no surgical deaths. These results confirm the feasibility of relieving a variety of serious arrhythmias by surgical intervention. PMID- 4032650 TI - Predictors of low and very low birth weight and the relation of these to cerebral palsy. AB - In a large prospective study, we investigated predictors of moderately low (1,501 to 2,500 g) and very low (less than 1,501 g) birth weight. Maternal age, height, and socioeconomic status, related to moderately low birth weight on univariate analysis, were not on multivariate analysis significant predictors for either low birth-weight outcome. The leading predictors of very low birth weight were low weight (less than 2,000 g) of last live birth, fetal malformation, nonwhite race, early vaginal bleeding, cigarette smoking, and chorionitis. Some of these were also predictors of moderately low birth weight. About 20% of births under 1,501 g could be attributed to chorionitis, a characteristic of less than 3% of the births. Of the major predictors of low birth weight, only prolonged rupture of membranes, chorionitis, and congenital malformations contributed to the risk of cerebral palsy beyond their contribution to the risk of low birth weight. PMID- 4032651 TI - Screening procedures in the asymptomatic adult. Comparison of physicians' recommendations, patients' desires, published guidelines, and actual practice. AB - To assess attitudes and practices regarding screening tests and preventive procedures, we surveyed 83 physicians in a hospital-based ambulatory care practice and compared their recommendations with the recommendations in published guidelines, the desires of 188 of their own patients, and the physicians' actual practice patterns on the surveyed patients. The surveyed physicians recommended screening procedures more frequently than the published guidelines in 48 situations and less frequently in 18 situations. Physicians at earlier levels of training tended to recommend more procedures than those who had completed training. Patients desired far more frequent screening than recommended either by their physicians or by the published guidelines. Physicians did not live up to their own recommendations for four of 14 procedures or to published guidelines for five of 14 procedures, with such failure occurring principally in situations where the test or procedure would normally be done personally by the physician. PMID- 4032653 TI - Life-threatening complications of sickle cell disease in children. PMID- 4032652 TI - Nausea, vomiting, and epigastric pain in an elderly diabetic. PMID- 4032654 TI - Multiphasic screening: panacea or diagnostic nightmare? PMID- 4032655 TI - Medical education in the United States 1984-1985. PMID- 4032656 TI - 85th annual report on medical education in the United States. Executive summary. PMID- 4032657 TI - Recent events of special interest to medical education. PMID- 4032658 TI - Undergraduate medical education. AB - There were 35,944 applicants for the 1984-1985 year in US medical schools. Of this number, 17,194 were accepted by at least one school. First-year enrollment equaled 16,992. Be-accepted by at least one school. First-year enrollment equaled 16,992. Because some students were repeating the first year, the number of first time enrolled students was 16,459. This represents a decrease of 113 from the previous year. The number of students enrolled in 127 US medical schools in 1984 1985 was 67,090; of this number, 21,287 (31.7%) were women. The estimated number of graduates in 1984-1985 was 16,347. The total enrollment of students of minority groups was 10,552 (15.7%), of which 3,663 (5.5%) were black not of Hispanic origin. The number of full-time medical school faculty was 58,767, another 123,002 were part-time or volunteer faculty. Medical school faculties also have teaching responsibility for a variety of other students, in addition to patient care and research responsibility. The average time needed to complete the curriculum requirements leading to the MD degree is 153 weeks. Twenty-one medical schools offered a combined college-medical school program. The length of these combined programs averaged 262 weeks. Ninety-six percent of students entering medical school in 1984-1985 had completed at least four years of college. More than two fifths of students had a premedical GPA of 3.6 or higher. PMID- 4032659 TI - US medical school finances. PMID- 4032660 TI - Continuing medical education. PMID- 4032661 TI - Allied health education and accreditation. PMID- 4032663 TI - Medical schools in Canada. PMID- 4032662 TI - Medical schools in the United States. PMID- 4032664 TI - Allied health education. PMID- 4032665 TI - New U of I eye center becomes Lions' pride. PMID- 4032666 TI - Botulinum toxin may help blepharospasm sufferers. PMID- 4032667 TI - Registry pools reports on ocular side effects. PMID- 4032668 TI - Leads from the MMWR. Oral viral lesion (hairy leukoplakia) associated with acquired immunodeficiency syndrome. PMID- 4032669 TI - Leads from the MMWR. Status of the 1990 physical fitness and exercise objectives. PMID- 4032670 TI - Vitamin D and hypercalcemia. PMID- 4032671 TI - Differentiating cervical lipomas from thyroid nodules. PMID- 4032672 TI - Turtleneck turns. PMID- 4032673 TI - Anisocoria from scopolamine patches. PMID- 4032674 TI - Sniffing up trouble: inhalation of volatile substances. PMID- 4032675 TI - Syphilis in the elderly. PMID- 4032676 TI - Routine urinalysis: is the dipstick enough? PMID- 4032677 TI - False-positive hematuria. PMID- 4032678 TI - Cardiac complications following tricyclic antidepressant overdose. Issues for monitoring policy. AB - Thousands of people in the United States poison themselves with tricyclic antidepressants each year. While these patients often require cardiac monitoring for potential arrhythmias, clinical practice is highly variable in regard to the hours of monitoring required. Clarification of this issue is important because of the impact on resources. This study retrospectively reviews the monitoring practices and cardiac complications following tricyclic antidepressant overdose in 75 adults. The patients received an average of 61.7 hours of monitoring. The vast majority of electrocardiographic changes, including three cardiac arrests, appeared within the first 24 hours. No patient with a normal level of consciousness and a normal electrocardiogram for 24 hours went on to develop any significant arrhythmia. On the basis of these data and an extensive literature review, we propose that current guidelines for cardiac monitoring following tricyclic antidepressant overdose be reconsidered. PMID- 4032679 TI - Screening for hypothermia in the ambulatory elderly. The Maine experience. AB - This study investigated the prevalence of low body temperatures in 97 elderly and 20 nonelderly subjects. To the best of our knowledge, no earlier survey has been conducted with a North American population. To ensure comparability with the British National Survey performed in 1973, urine temperatures were collected as a proxy measure of core temperatures. The urine-collecting funnel was modified to minimize cooling artifact introduced by the device. Study subjects were selected from an internal medicine clinic that serves the poor, a federally subsidized housing project, and a subsidized housing project in northernmost Maine. A youthful population (mean age, 32.3 years) was chosen to provide a comparative population to elderly participants (mean age, 73.9 years). Based on the British National Survey, the expected prevalence of low body temperatures (less than 35.5 degrees C) was 10%. The present study detected no low body temperatures, and the average urine and mouth temperatures were 0.3 and 0.19 degree C warmer, respectively, than those in the British National Survey. Youthful subjects were not significantly different from elderly participants. There appears to be no evidence from this study that low early-morning basal body temperature (less than 35.5 degrees C) is a common geriatric occurrence in ambient room temperature. PMID- 4032680 TI - How many doctors do we need? The tenth annual Duke Private Sector Conference. PMID- 4032681 TI - Righting medical writing. PMID- 4032682 TI - Nitrogen versus muscle calcium in the genesis of abnormal muscle function in malnutrition. PMID- 4032683 TI - Elimination of lipofundin S during the intravenous fat tolerance test in patients with low, medium, and high fasting triglyceride concentrations. AB - The intravenous fat tolerance test with Lipofundin S (0.5 ml of 20% emulsion/kg body weight) was performed in 22 male nondiabetic patients. According to their fasting triglycerides (TG), the patients were arranged into three groups: low (less than 2.8 mmol/liter), medium (2.8-5.7 mmol/liter), and high (greater than 5.7 mmol/liter) concentrations. Fractional elimination rates of injected Lipofundin S decreased from 11.08 in low TG to 4.57%/min in high TG; they were positively correlated with fasting levels of high-density lipoprotein cholesterol but negatively with those of TG. The same pattern of correlations was observed with fractional catabolic rates of endogenous TG as measured after injection of tritium-labeled glycerol. The intravenous Lipofundin S load effected transient TG and free fatty acid elevations which were delayed in high TG. The elimination mechanisms of injected Lipofundin S and of endogenous TG are compared. PMID- 4032684 TI - A technique for tunneling central venous catheters. AB - Tunneling the central venous catheter from the venous insertion site in the subclavicular or cervical area to the exit site on the chest wall can be difficult, especially in small children with a very convex chest wall. We present a technique which avoids many of the problems encountered with previously described methods. PMID- 4032685 TI - Ventricular arrhythmias late after aortic and/or mitral valve replacement. AB - Since it is not yet known whether ventricular arrhythmias in patients with valve replacement are associated with an increased risk of sudden death, as in patients with coronary artery disease, a total of 46 patients who were long-term survivors of aortic and/or mitral valve replacement were examined with 24-hour ambulatory electrocardiographic monitoring, and the factors influencing the occurrence of ventricular arrhythmias were analyzed. The significance of ventricular arrhythmias in the prognosis of valve replacement is discussed. The occurrence of ventricular arrhythmias was significantly higher: 1) in patients with aortic stenosis than in those with aortic regurgitation, 2) in patients with multiple valve surgery than in those with single valve replacement and 3) in patients with larger heart size. Pre- and postoperative hemodynamics, including left ventricular function, were not significantly related to the incidence of ventricular arrhythmias. A review of the patients who died suddenly, late after valve replacement suggests that frequent ventricular arrhythmias and thromboembolism are the most important factors in the late mortality of these patients. The prognostic significance of postoperative ventricular arrhythmias in patients with valve replacement requires additional study. PMID- 4032686 TI - Macroscopic hemorrhagic infarction following selective coronary thrombolysis in acute myocardial infarction. AB - Macroscopic hemorrhagic infarction was studied in 14 autopsied hearts with selective coronary thrombolysis (SCT) after acute myocardial infarction (AMI). In all patients urokinase, 240,000 - 720,000 units, had been selectively injected into ischemia-related coronary artery at 2 - 7 hours after the onset of AMI. The degree of stenosis after SCT was 90 - 99% in 13 patients and 100% in one patient. According to the duration of illness at death, the 14 patients were classified into 3 stages; stage I: 4 - 9 hours; stage II: 15 hours to 11 days; stage III: 19 days to 12 months. Three hearts in stage I had no macroscopic hemorrhage. In stage II, marked and diffuse hemorrhage in the infarct area was macroscopically evident in 6 of 7 hearts. In a stage II patient, extravasation of contrast medium into the myocardium was found at 3 hours after the onset of AMI. In stage III, 4 hearts had massive fibrosis or granulation in the left ventricular wall without macroscopic hemorrhage. Cardiac rupture was seen in 4 of 10 patients from stages I and II. It is concluded that macroscopic bleeding appears in most patients with AMI treated with coronary thrombolysis. In the majority of cases, the hemorrhage increases gradually after SCT and becomes macroscopically definite approximately 15 hours after the onset of AMI. Rarely, massive bleeding appears earlier. Hemorrhagic infarction is replaced by massive fibrosis after approximately 2 weeks. PMID- 4032687 TI - [Effect of nicardipine on airway dynamics during general anesthesia]. PMID- 4032688 TI - [In vivo time lag and response time of transcutaneous oxygen monitoring]. PMID- 4032689 TI - [Hematological changes in open heart surgery, with special reference to hypothermic anesthesia]. PMID- 4032690 TI - [Changes in canine intrahepatic blood flow distribution under inhalational anesthetics]. PMID- 4032691 TI - [Metabolic and endocrine responses to anesthesia and surgery during trimetaphan infusion]. PMID- 4032692 TI - [Antihypertensive effect of nasal nifedipine and its plasma concentration during anesthesia and surgery]. PMID- 4032693 TI - [Hemodynamic response to infrarenal aortic clamping and declamping and graphical analysis of ventricular functions]. PMID- 4032694 TI - [Hormonal response to infrarenal aortic cross-clamping and declamping]. PMID- 4032695 TI - [Side effects of epidural morphine with special reference to age and sex]. PMID- 4032696 TI - [The maximum surgical blood order schedule (MSBOS) in oral surgery]. PMID- 4032697 TI - [Anesthesia for a patient with myotonic dystrophy]. PMID- 4032698 TI - [Anesthesia for a patient with Holt-Oram syndrome]. PMID- 4032699 TI - [Neuromuscular blocking action of trimethaphan camsylate and cholinesterase]. PMID- 4032700 TI - [The need for nitrous oxide anesthesia--a questionnaire]. PMID- 4032701 TI - [Isoflurane (Forane), a new inhalation anesthetic agent]. PMID- 4032703 TI - [Changes in acid-base balance in arterial blood and cerebrospinal fluid (CSF) during hypothermia anesthesia]. PMID- 4032702 TI - [Effect of increased intracranial pressure on coronary circulation]. PMID- 4032704 TI - [The decrease in cardiac output by the continuous administration of calcium chloride after hemorrhagic shock]. PMID- 4032705 TI - [The effects of preanesthetic intramuscular ranitidine on the volume of gastric aspirates and the pH in emergency patients]. PMID- 4032706 TI - [The information management of anaesthesia for patients with rheumatoid arthritis by using a microcomputer]. PMID- 4032707 TI - [A case of malignant hyperthermia; successful treatment with intravenous dantrolene sodium]. PMID- 4032708 TI - [Anesthetic management of a patient with Dejerine-Sottas disease]. PMID- 4032709 TI - [Anesthetic management of a patient with congenital bronchobiliary fistula]. PMID- 4032710 TI - [Usefulness of the Swan-Ganz pacing thermodilution catheter for patients with cardiac disease]. PMID- 4032711 TI - [Cryoanalgesia for postthoracotomy pain]. PMID- 4032712 TI - [The hematological and immunological effects of platelet concentrate transfusions on surgical patients in platelet depleted states]. PMID- 4032713 TI - [Postoperative blood coagulation disorders and their management]. PMID- 4032714 TI - [Phase I clinical studies of S6472 (sustained release preparations of cefaclor)]. AB - Current (regular) preparation of cefaclor (CCL) require the 3-time-a-day administration. S6472 (sustained release preparation) which can be used with the twice-a-day administration in the morning and the evening is capsule and granule preparations consisting of 40% of nonenteric and 60% of enteric coated granules of CCL. Phase I clinical studies of S6472 were conducted in 12 nonfasted healthy adult male volunteers with cross over method using a single dose of 375 mg in capsule and granule forms of S6472, and 250 mg in capsule form of regular CCL as a control drug. The volunteers received the 3 preparations at 1-week interval. The summary of the results from the above studies is as follows: Grouping of the volunteers. The 12 volunteers were divided into 3 groups (each group consists of 4 volunteers) and there were no significant differences between each group regarding background factors of the volunteers. Tolerance. None of the volunteers who received the 3 preparations at 1-week interval complained of subjective abnormalities. No abnormalities which are considered to be due to S6472 and regular CCL were found in the clinical laboratory tests carried out before the administration and 1 week after the completion of the studies. Plasma level. There were no significant differences between capsule and granule forms of S6472 regarding Cmax and AUC, and it was confirmed that bioavailability of both preparations was the same. It was also confirmed that plasma levels of the 2 preparations of S6472 were maintained for longer period of time than those of regular CCL. Urinary excretion. Mean urine levels of the 2 preparations of S6472 every 2 hours after the administration were confirmed to be maintained for longer period of time than those of regular CCL. There were no significant differences between the 2 preparations of S6472 regarding urinary recovery rate. However, the significant differences between the 2 preparations of S6472 and regular CCL were observed. Urinary recovery rate of the 2 preparations of S6472 was 87 approximately 88% of that of regular CCL. PMID- 4032715 TI - [Absorption and excretion studies of S6472 (sustained release preparations of cefaclor)]. AB - In order to see absorption and excretion of S6472 (sustained release preparations of cefaclor (CCL], 3 studies regarding, 1) influence of meals (single dose of 375 mg in capsule form), 2) dose response (single dose of 375 mg vs. 750 mg in granule form) and 3) continuous administration (twice-a-day administration of 750 mg in granule form for 8 days) were conducted in 15 healthy adult male volunteers using capsule and granule forms of S6472. The following is the summary of the results from the above studies: Tolerance. In the above 3 studies, none of the 15 volunteers complained of subjective abnormalities. In the clinical laboratory tests performed before the administration of S6472 and at the next day of the completion of the studies, the values from the laboratory tests were within normal range. Influence of meals. The average time for peak plasma level of CCL and decrease in the plasma level following the administration of S6472 were the fastest in the fasted volunteers, followed by the volunteers with light meals and usual meals. From this, it was confirmed that plasma levels of CCL were maintained for longer period of time in the non-fasted volunteers than in the fasted volunteers. In the volunteers who had light and usual meals, the peak plasma levels, AUC of the plasma levels and urinary recovery rate were almost the same. Influence by amount of meals was scarcely observed. Dose response. Mean serum levels and their AUC in the volunteers receiving 750 mg of S6472 were approximately twice as much as those in the volunteers receiving 375 mg of S6472, and dose response between the 2 doses was confirmed. Continuous administration. Mean serum levels and their AUC at the first dose and the 15th dose (final dose) were almost the same. In the continuous administration of S6472 for 8 days (15 doses), no accumulation of CCL in the body was observed. PMID- 4032716 TI - [Fundamental and clinical studies of cefpimizole in obstetrics and gynecology]. AB - The findings from recent fundamental and clinical studies of the efficacy of cefpimizole (AC-1370) in obstetrics and gynecology are reported in this paper. The AC-1370 concentrations in genital tissues sampled 30 to 56 minutes (a mean of 41.4 minutes) after intravenous injection of 1 g of the drug were 14 to 76 micrograms/g (a mean of 32.4 micrograms/g). The mean transfer ratios of the drug into the genital tissues to the concentration in the uterine arterial blood were such that the transfer ratio into the portio vaginalis was the highest, followed by the uterine cervix and the myometrium, and that into the oviduct was the lowest with about 1/2 that into the portio vaginalis. The concentration in the antecubital venous blood and that in the uterine arterial blood remained similar for all patients. The transfer of AC-1370 into the pelvic dead space exudate reached a peak (49.5 micrograms/ml) 1 hour, and also a peak (49.8 micrograms/ml) 2 hours after the intravenous injection. It then decreased gradually, but remained high, being higher than that in the antecubital venous blood about 50 minutes after the intravenous injection. Ten patients with infections in gynecology were treated with 1.0 to 4.0 g daily of AC-1370, to a total dose of 6 to 52 g, over a period of 3 to 13 days. One of them showed excellent response, 8 showed moderate response, and another showed poor response to the treatment: in other words, a response rate of 90% was achieved. Bacteriologically, pathogens were eradicated from 3 and decreased in 3, and microbial substitution occurred in another patient. No side effects of the drug were observed except for eruption in 1 patient. None of the 10 patients showed any abnormalities in laboratory findings. From the present fundamental and clinical studies of AC-1370, we have drawn the conclusion that the drug is one of extremely useful antibiotics in the treatment of infections in obstetrics and gynecology. PMID- 4032717 TI - [Fundamental and clinical studies on cefpimizole in the field of obstetrics and gynecology]. AB - Cefpimizole (AC-1370), a new cephem antibiotic, was studied in the field of obstetrics and gynecology, fundamentally and clinically. And the following results were obtained. The concentrations of the drug in uterine arterial and cubital venous blood, and internal genital organs following intravenous drip infusion were measured. The results demonstrated favourable transfer of the drug into the various internal genital organs. Four patients with obstetric and gynecological infections were treated with AC-1370. The therapeutic results were good in 3, and poor in 1 case, therefore the effective rate was 75%. No side effects were noted in any cases, but the severe eosinophilia (37%) was found in 1 patient. It is therefore presumed that AC-1370 is a useful drug for infectious diseases in the field of obstetrics and gynecology. PMID- 4032718 TI - Clinical study of cefpimizole in obstetric and gynecologic infections. AB - The use of cefpimizole (AC-1370) in 11 patients with a variety of obstetric and gynecologic infections was studied. Although the activity of AC-1370 was found in vitro less eminent than those of currently employed antibiotic regimens, the overall clinical response was 82%. No side effects were found. PMID- 4032719 TI - [Fundamental and clinical studies on cefoperazone in pediatrics, with special reference to renal toxicity]. AB - Fundamental, clinical studies on cefoperazone (CPZ), a new synthetic antibiotic of cephalosporins was conducted to obtain results as follows. This preparation, 11.4-50 mg/kg was administered to 11 cases of children by intravenous drip infusion for 30 minutes, and serum levels were studied. The highest serum level at the completion of infusion was 40.0-138.0 mcg/ml. A dose response was observed. The half-life in serum averaged 1.55 hours except 2.4 hours observed with 1 case of liver dysfunction. When the urinary excretion during 30 minutes drip infusion was examined, the urinary recovery rate at 0-6 hours in 2 cases of children averaged 17.2% and was low at 5.3% in 1 case of membranoproliferative glomerulonephritis. In terms of the clinical effect on bacterial infections in pediatric field, CPZ proved effective in all of the 21 cases in which it was used alone. And it showed an excellent antibacterial activity against all the bacteria isolated from cases used as the subjects. When side effects were studied, diarrhea and slight impairment of the liver were observed, but all were transient. As a result of a study on the renal toxicity of CPZ, CPZ was deemed as being a drug which hardly causes disturbance of renal tubules judging from the aspect of the beta-D-N-acetylglucosaminidase activity in urine and variations in the urine beta 2-microglobulin levels. PMID- 4032720 TI - [Clinical studies of intravenous drip infusion of micronomicin. 1. Pharmacokinetics (Part 2). Intravenous Micronomicin Research Group]. AB - Following the previous report on pharmacokinetics of micronomicin (MCR) in healthy volunteers, pharmacokinetic studies were made again in patients with different degree of renal impairment, and a nomogram was obtained. MCR at a dose of 60 mg/time was given by 1-hour drip infusion to 14 inpatients who consented to receive MCR (age: 35 to 84 years, Ccr: 17.96 to 104.35 ml/min). The blood collection was performed in accordance with the schedule made upon the degree of renal impairment, and the serum concentration was determined by HPLC method. The results were analyzed by MULT program using two- or one-compartment open model. The serum concentration (Cmax) just after administration of MCR was 5.8 +/- 0.9 microgram/ml (mean +/- S.D.). The biological half-life was 1.81 to 12.35 hours. Taking the above results into consideration together with the previous ones of healthy males, the following correlation was obtained between the elimination constant (Kel or beta) and Ccr calculated from S-Cr.: Kel or beta = 0.0038 X Ccr 0.0097. Further, no side effect was observed in these studies. Elimination of MCR from blood was dependent on renal function like other aminoglycosides, and so it was possible to estimate the elimination constant from Ccr. From these results, a nomogram for the optimum dosage regimen of MCR was obtained. PMID- 4032721 TI - [Absorption, distribution, metabolism and excretion of bacmecillinam. I. Absorption, distribution, metabolism and excretion of 14C-bacmecillinam following oral administration to rats]. AB - The pharmacokinetics of bacmecillinam (KW-1100), a new semisynthetic penicillin, was studied. Plasma levels, tissue distribution, metabolites and urinary and biliary excretion of mecillinam after oral administration of KW-1100 were studied in rats given a dose of 20 mg/kg (as mecillinam). The absorption of 14C-KW-1100 was so rapid that the level in blood was found to reach the peak 30 minutes after administration. 14C-KW-1100 was distributed widely into various tissues and relatively high distribution was noted in liver, kidney, adrenal gland and spleen. No accumulation of 14C-KW-1100 in any tissue was found. It was excreted rapidly from each tissue. Within 24 hours after administration of KW-1100, approximately 86% of the given dose was excreted. And within 72 hours, approximately 97% of the dose was excreted. Excretions in urine and feces within 72 hours after KW-1100 administration were 39.5 and 57.4% of the given dose, respectively. Biliary excretion was 2.0% of the given dose within 24 hours after administration of KW-1100. The major metabolite in the plasma at peak time (30 minutes) was mecillinam (50.5%). The major metabolite in the urine (0 approximately 8 hours) was mecillinam (52.2%), too. The minor metabolites were 5,5-dimethyl-2-(1'-formamidomethyl)-thiazolidine-1',4-dicarboxylat e(M-1), 6-beta [(hexahydro-1H-azepin-1-yl)-methyleneamino]-penicilloic acid (M-6) and M-4. PMID- 4032722 TI - [Absorption, distribution, metabolism and excretion of bacmecillinam. II. The placental transfer and transition into milk of 14C-bacmecillinam]. AB - The placental transfer and transition into milk of bacmecillinam (KW-1100), a new semisynthetic penicillin, have been studied with 14C-KW-1100 administered orally in the pregnant and lactating rats, respectively. The level of 14C-KW-1100 in the umbilical cord blood was 7.2% of the peak maternal blood level and the radioactivity was eliminated slowly. At the peak fetus level (4 hours after administration), the radioactivity transferred into the fetuses was found to be 0.01% of the dose. 14C-KW-1100 was distributed into the uterus, ovary, placenta and consistently into the fetal membrane. 14C-KW-1100 was excreted into milk slightly, and the concentration of radioactivity in milk did not exceed the maternal peak blood level. PMID- 4032723 TI - [Absorption, distribution, metabolism and excretion of bacmecillinam. III. Absorption, metabolism and excretion of 14C-bacmecillinam following oral administration to dogs]. AB - The pharmacokinetics (i.e., blood level, biological half-lives and excretion) of bacmecillinam (KW-1100) was investigated. KW-1100 was orally administered to dogs at the dose of 20 mg/kg (as mecillinam). Biological half-lives (radioactivity) of 14C-KW-1100 in plasma were 1.2 hours (T1/2 alpha) and 52 hours (T1/2 beta). The Cmax and Tmax were 8.4 micrograms/ml and 2 hours. The biological half-life (microbiological activity) of KW-1100 in plasma was 0.9 hour. The Cmax and Tmax were 5.6 micrograms/ml and 1 hour. The urinary and fecal excretion of 14C-KW-1100 were approximately 46% and 49% (0 approximately 72 hours), respectively. The major metabolites in the urine (0 approximately 8 hours) were mecillinam, 5,5 dimethyl-2-(1'-formamidomethyl)-thiazolidine-1',4-dicarboxy lat e (M-1) and 6 beta-[(hexahydro-1 H-azepin-1-yl)-methyleneamino]penicilloic acid (M-6), each distribution ratio of which was 57.2, 24.2 and 12.0% of the total radioactivity in the sample, respectively. The major metabolite in the plasma at peak time (2 hours) was mecillinam (56.2%). PMID- 4032724 TI - [Absorption, distribution, metabolism and excretion of bacmecillinam. IV. Metabolites of bacmecillinam in human urine]. AB - Bacmecillinam (KW-1100) metabolites and their excretion in human urine were investigated in the 3 male volunteers. After administration of KW-1100 capsules containing 80 mg (2 X 40 mg) as mecillinam to men, the urine samples up to 8 hours were collected for every 2 hours and analysed by high performance liquid chromatography and gas chromatography. The major metabolites in the human urine were mecillinam and 6-beta-[(hexahydro-1H-azepin-1-yl)-methyleneamino] penicilloic acid (M-6), and minor quantities of M-4 and M-1 were also detected as the metabolites. Total recoveries of administered dose for the 3 volunteers were approximately 62, 81 and 73%, respectively. And M-1 excretion rate was lower than that in the case of rats and dogs. Hexamethyleneimine (HMI) as metabolite from the side chain was detected. PMID- 4032725 TI - [Cefaclor dosage change with renal dysfunction]. AB - Serum and/or urine levels of cefaclor (CCL) were studied in 4 patients during the therapy with CCL. In patients with severely impaired renal function, moderately higher serum and urine levels of CCL persisted, serum half-lives of CCL were moderately prolonged and urinary excretion of CCL slightly decreased. Although dosage modification of CCL is necessary in patients with renal dysfunction, multiple doses of 250 mg every 8 hours may be safe and effective even in patients with impaired renal function. PMID- 4032726 TI - [Fundamental and clinical studies on cefpimizole in the field of obstetrics and gynecology]. AB - Fundamental and clinical studies on cefpimizole (AC-1370), a new cephalosporin derivative, in the field of obstetrics and gynecology have been investigated, and the following results were obtained. High concentrations of AC-1370 in internal genital organs were detected after intravenous administration of 1.0 g of AC 1370. In the treatment of 14 cases of infection, the therapeutic effects were excellent or good in 11 cases and overall efficiency rate excluding 1 case with side effects was 84.6% (11/13). No serious side effect was observed except 1 case of nausea and vomiting. PMID- 4032727 TI - [Clinical efficacy of cefpimizole in inflammatory diseases in the field of gynecology]. AB - Clinical study to evaluate the usefulness of cefpimizole (AC-1370) was made in the 6 patients with female genital organ infections. Two grams or 4 g of AC-1370 was administered a day by intravenous drip infusion ranging from 5 to 18 days. Responses were excellent in 2 cases, good in 3 cases and poor in 1 case, parametritis after hysterectomy. The efficacy rate was 83%. Neither general side effect nor abnormal laboratory finding was observed. AC-1370 showed a satisfactory clinical efficacy in treatment of the infections in the field of gynecology, and it has been concluded that AC-1370 will be an useful antibiotic for these infections. PMID- 4032728 TI - [Evaluation of the clinical effect and tissue distribution of cefpimizole in the field of gynecology]. AB - Cefpimizole (AC-1370) was administered to 5 cases with uterine myoma before hysterectomy, and tissue distribution was determined. AC-1370 was also administered to 5 cases with gynecological infections. The following results were obtained. One gram of AC-1370 was administered from 43 to 299 minutes before hysterectomy, tissue distribution of AC-1370, such as ovary, oviduct, myometrium, cervix uteri, and portio vaginalis was showed the highest level (30.0 approximately 49.5 micrograms/g) at 43 minutes after administration, and these were 39.0 approximately 64.4% of the concentration in uterine arterial blood. Tissue concentration of AC-1370 was then gradually decreased following with the decreasing of the concentration in uterine arterial blood. AC-1370 was administered to 3 cases with pyometra, 1 case with Bartholin abscess, 1 case with adnexitis. The clinical efficacy was good in all 5 cases. Bacteriological study revealed that A. faecalis and E. coli were eradicated, but B. fragilis was persisted. No side effect was observed in all cases. PMID- 4032729 TI - [Application of cefpimizole in obstetrics and gynecology]. AB - We made fundamental and clinical studies of a new cephalosporin derivative, cefpimizole (AC-1370). AC-1370 was relatively efficiently transferred into the uterine adnexa; in other words, it was as well transferred into the tissues as the other cephalosporin derivatives. There seemed to be no specific relation between its blood level and its level in any tissue. In 1 patient treated with AC 1370 for postoperative infection, clinical findings, WBC and CRP improved: the drug was evaluated as effective. Neither hepatic nor renal function was impaired in the patients treated with AC-1370 in the fundamental and clinical studies of the drug. PMID- 4032730 TI - [Pharmacokinetics and clinical studies on cefpimizole in the field of obstetrics and gynecology]. AB - Cefpimizole (AC-1370), a new cephem antibiotic, was studied in the field of obstetrics and gynecology, and the following results were obtained. The absorption and tissue penetration of AC-1370 into intrapelvic genital organs were good. The peak serum level in the uterine artery after an intravenous drip infusion for 30 minutes was 49.0 micrograms/ml. High concentrations were obtained also in genital organ tissues; the maximum concentrations were 24.4 approximately 39.0 micrograms/g after an intravenous drip infusion. The changing patterns of the tissue concentrations were similar to those in the serum. The penetration of AC-1370 into intrapelvic dead space exudate was good. The level reached a peak of 35 micrograms/ml at 2 approximately 4 hours after an intravenous drip infusion with 1 g and 3.7 micrograms/ml after 12 hours. AC-1370 was effective in 20 out of 21 cases (95.2%) with gynecoobstetrical infections such as intrauterine, intrapelvic infection and mammitis, administered with 1 approximately 2 g twice a day. Few side effects were observed. PMID- 4032731 TI - [Fundamental and clinical studies on cefpimizole in the field of obstetrics and gynecology]. AB - Cefpimizole (AC-1370) was studied for its transference into adnexa uteri and uterine tissues as well as for its effects and safety on gynecological infections. The results obtained are as follows: Peak levels of AC-1370 were obtained in the antecubital vein and uterine artery at 10 minutes, in the tissues of adnexa uteri and uteri about 30 minutes after one shot intravenous injection of AC-1370 1 g, and relatively high concentrations were maintained for several hours. In the treatment of 30 cases of gynecological infections, the clinical efficacy of AC-1370 was assessed as effective in all cases. As for the bacteriological effects of AC-1370, 77.6% of isolated organisms were eradicated and 90% of all cases were effective. Side effects and abnormal laboratory findings due to AC-1370 were not observed during and after administration. PMID- 4032732 TI - [Fundamental and clinical studies of cefpimizole in the field of obstetric and gynecologic infections]. AB - We made fundamental and clinical studies of a new cephalosporin derivative cefpimizole (AC-1370), and found the following. In 7 patients treated with AC 1370 for the fundamental study of the drug, the blood level of the drug in the uterine artery scarcely differed from that in the elbow vein, and it decreased steadily with time. It remained to be 6.5 approximately 7.0 micrograms/ml 5 hours after intravenous injection of 1 g of the drug. The tissue-serum concentration ratio of the drug was 122 approximately 58% in the portio vaginalis where the drug was transferred at the highest level, and 56 approximately 114% in the oviduct where it was transferred at the lowest level; the mean level was 61.5%. The responses to AC-1370 of 10 patients with genital infections were excellent in 1, good in 8 and poor in the other, with a response rate of 90%. Bacteriologically, pathogens were eradicated in 3, decreased in 2, and the response was unknown in the other 5. No side effects or abnormal laboratory findings were noted except for leukopenia in 1 patient. PMID- 4032733 TI - [Laboratory and clinical studies on cefpimizole in the field of gynecology]. AB - Cefpimizole (AC-1370), a new cephalosporin antibiotic, was evaluated for its distribution in uterine tissue, penetration into retroperitoneal exudate and therapeutical effects on some infections in gynecology. The following results were obtained; The levels of AC-1370 in the cubital vein were similar to those in the uterine artery and this remained in the course of examinations after an 1 g intravenous injection. Seven patients with gynecological infections received AC 1370 by intravenous injection. The overall efficacy rate was 85.7%. No adverse reaction was observed in any of the cases treated with AC-1370, nor was there any marked changes in the laboratory findings. PMID- 4032734 TI - [Fundamental and clinical studies of cefpimizole in obstetrics and gynecology]. AB - Cefpimizole (AC-1370) concentrations in the pelvic dead space exudate were determined in patients under-going curative resection of carcinoma of the uterine cervix to study the transfer of the drug into the female genital organs, and the results were statistically analyzed, using the two-compartment model. When 1 g of AC-1370 was administered by intravenous drip infusion over 1 hour, the AC-1370 concentration in the serum from the antecubital vein reached a level of 129.09 micrograms/ml at 1 hour of intravenous drip infusion, and the AC-1370 concentration in the pelvic dead space exudate reached a peak of 30.32 micrograms/ml at 2.51 hours of intravenous drip infusion, and remained at not less than 12 micrograms/ml 8 hours after the beginning of the drip infusion, with the area under the curve (AUC) for the AC-1370 concentration in the pelvic dead space exudate being 213.66 micrograms X hr/ml. Seven patients with obstetrical and gynecological infections were treated with 1 g of AC-1370 by intravenous drip infusion over 1 hour, 2 approximately 3 times daily. Although the patients all had rather mild infections, the treatment was effective in all of them. The findings in this study proved a dose of 1 g of AC-1370 at a time to be sufficiently effective in mild cases, but in view of the transfer of the drug into tissues, it seemed necessary to administer 2 g of the drug at a time in severe cases. PMID- 4032735 TI - [Fundamental and clinical studies on cefpimizole in the field of obstetrics and gynecology]. AB - Fundamental and clinical studies on cefpimizole (AC-1370), a new cephem antibiotic, were performed and the following results were obtained: Concentration of AC-1370 was examined in serum, internal genital organs and retroperitoneal fluid after single intravenous administration of 2.0 g dose. The venous serum level of AC-1370 was 243 micrograms/ml at 30 minutes after the administration. The sufficient transfer of AC-1370 to internal genital organs and retroperitoneal fluid was recognized. In clinical trial, AC-1370 was given to 10 cases with obstetrical and gynecological infections. The efficacy was evaluated as good in 8 cases and poor in 2 cases. No side effects were observed in any of the cases treated with AC-1370. PMID- 4032736 TI - [Fundamental and clinical studies on cefpimizole in the field of obstetrics and gynecology]. AB - The findings from fundamental and clinical studies on cefpimizole (AC-1370) in the treatment of infections in obstetrics and gynecology are reported. We investigated the transfer of AC-1370 into female genital tissues of 6 patients and the transfer of the drug into the pelvic dead space exudate in 9 patients by means of determining its concentrations in the tissues 90 to 210 minutes after the end of intravenous drip infusion of the drug over 1 hour. The mean concentration was 13.06 micrograms/g for the oviduct, 16.50 micrograms/g for the ovary, 16.50 micrograms/g for the endometrium, 14.92 micrograms/g for the myometrium, 16.58 micrograms/g for the uterine cervix, 17.75 micrograms/g for the portio vaginalis, 10.46 micrograms/ml for the uterine arterial serum and 9.91 micrograms/ml for the antecubital venous serum. The drug proved to be well transferred into the pelvic dead space exudate; it reached a peak of mean 2 hours after the end of the intravenous drip infusion of the drug over 1 hour, then decreased steadily, and was found to be a mean of 16.7 micrograms/ml even 8 hours after the end of the intravenous drip infusion. Four patients with infections in obstetrics and gynecology were then treated with AC-1370. Three out of the 4 patients responded to the treatment, while the response of another patient was unknown. None of the 4 patients showed any side effects of the drug or any abnormalities in laboratory findings. PMID- 4032737 TI - Normal vectorcardiographic parameters in infants and children. AB - Normal ranges of 32 parameters in vectorcardiography were determined in 200 healthy infants and children. The subjects were divided into 5 groups and results were compared in each group. Significant differences were found in 11 parameters. The differences were associated with a physiologically prominent right ventricular load in younger age groups. Therefore, age should be considered in evaluation of vectorcardiography. PMID- 4032738 TI - Dipolarity and dipole location during QRS and T waves in normal men estimated from body surface potential distribution. AB - The dipolarity of the body surface potential distribution and the locus of the main dipole were estimated mathematically at 2 msec intervals in 27 normal men. The nondipolar content showed time-dependent fluctuation during the QRS. It increased sharply at early and later phases of the QRS. The main dipole moved smoothly within the actual cardiac region and was inscribed in a clockwise direction in most cases. The nondipolar content during the ST-T period was smaller and with less fluctuation than that during the QRS. The main dipole during the T wave moved less than 2 cm near the center of the heart. These results indicated that although a fairly large percentage of the body surface potential could be represented by a single moving dipole, the nondipolar content was larger during initial and late phases of the QRS. It was also suggested that the ventricular repolarization process can be better approximated by a single fixed dipole in normal men. PMID- 4032739 TI - A new indirect method for measurement of sinoatrial conduction time and sinus node return cycle. AB - We developed a new indirect method for the measurement of sinoatrial conduction time (SACT) and the sinus node return cycle (SRC) with a transvenous catheter technique. Two early premature stimuli, at intervals 50 msec longer than the effective refractory period (ERP), were given to the right atrium. These early stimuli were followed by eight constant stimuli. The interval of the constant stimuli was a little shorter than the basic cycle length (BCL). The return cycle A1Ar was measured and plotted on the abscissa; the next interval ArA3, was measured and plotted on the ordinate. This was called the "base point". A new stimulus, A2, was then added to the train of stimulations, first at a point simultaneous with Ar. It was then shifted toward the last constant stimulus at 10 20 msec intervals until A2 met the ERP. The relationship between A1A2 and A2A3 was obtained by the repetition of the procedures with various A1A2 intervals. It had two zones, compensatory and non-compensatory. We postulate that the atriosinus conduction time of the last of the eight stimuli was equal to that of A2 when the stimulus A2 first captured and reset the sinus nodal pacemaker cells, as indicated by the transition point of the two zones. Based on this supposition, SACT and SRC could be measured as the intervals from the base point to the transition point and from the transition point to the eighth stimulus, respectively. PMID- 4032740 TI - Assessment of the contribution of atrial systole to ventricular filling by cardiac pacing. AB - Analysis of beat to beat changes in left ventricular (LV) ejection time during cardiac pacing was utilized to assess the atrial contribution to ventricular filling in 30 consecutive patients undergoing diagnostic cardiac catheterization. The group consisted of 9 normal subjects, 18 with coronary artery disease and 3 with congestive cardiomyopathy. The recordings of aortic pressure were made during atrial pacing and ventricular pacing at a rate 5 to 10 beats/min above each individual's sinus rhythm. During ventricular pacing, LV ejection time was the longest when an atrial contraction preceded a ventricularly paced beat by a physiologic interval and was approximately similar to that obtained during atrial pacing (maxET). When the atrial systole occurred with or followed the ventricularly paced contraction, LV ejection time was decreased (minET). Since maxET occurred in the presence of an effective atrial contraction to ventricular filling and minET in the absence of this contraction, the atrial contribution to ventricular filling was calculated as (maxET-minET)/maxET X 100 (%). LV volumes at end-systole (V1), before atrial contraction (V2) and at end-diastole (V3) were obtained according to the area-length method by tracing the silhouette of left ventriculograms using a computer system. The atrial contribution was calculated from LV volumes using the formula (V3-V2)/(V3-V1) X 100 (%). There was a good correlation (r = 0.88) between the atrial contributions calculated from LV ejection times and those calculated from LV volumes. In the patients with coronary artery disease and with congestive cardiomyopathy, the atrial contribution was significantly greater than in the normal subjects. The measurement of LV ejection time during ventricular pacing may be a clinically useful screening procedure to identify patients in whom physiologic pacing may be indicated. PMID- 4032741 TI - Two-dimensional echocardiographic method for the estimation of cardiac output independent of left ventricular geometry. Comparison with cardiac catheterization in mitral stenosis. AB - An hydraulic formula for the estimation of cardiac output independent of the geometric status of the left ventricle was studied by comparing the predictions based upon echographic and catheterization data with the results of the standard Fick principle method for cardiac output. The formula tested specifies cardiac output as Q = (1/21) RAT2, where Q is the cardiac output in ml, R is the heart rate, A is the mitral valve area in cm2 and T is the diastolic filling period in seconds per minute. Cardiac output estimated by this equation corresponds with cardiac output as determined by the Fick principle method at a level characterized by a correlation coefficient of r = 0.92 and a standard error of SE = 0.15 L/min for N = 26. The results suggest that the new expression may be useful for estimating cardiac output from echographic data. PMID- 4032743 TI - Evaluation of response to dopamine in idiopathic dilated cardiomyopathy by echocardiography and thallium-201 myocardial scintigraphy. AB - Twenty-six patients with idiopathic dilated cardiomyopathy (DCM) underwent thallium-201 myocardial scintigraphy. Nine patients (group A) showed a perfusion defect in the interventricular septum (IVS) and 7 patients (group B) showed a defect in the left ventricular posterior wall (LVPW). Hemodynamic responses and catecholamine levels were compared between 16 patients (DCM group) and 6 control subjects (control group) following dopamine infusion (6 micrograms/Kg/min). The end-diastolic thickness of the IVS and LVPW, and the percentage wall thickening were assessed by echocardiography. Plasma dopamine and norepinephrine concentrations in the DCM group were not different from those of the control group at rest. During the dopamine infusion, however, norepinephrine increased only in the control group. There were significant differences in the thickness of the IVS among the 3 groups [7.3 +/- 1.4 mm for group A (p less than 0.001 vs control and p less than 0.05 vs group B), 8.9 +/- 1.5 mm for group B (p less than 0.01 vs control), 10.2 +/- 1.5 mm for the control group]. The percentage thickening of the IVS increased during the dopamine infusion in group B only and the thickening of the LVPW increased in group A only. Thus, in the myocardium of DCM patients with thallium perfusion defects, the degree of thickening did not change during dopamine infusion, but in the myocardium of DCM patients with normal thallium uptake the percentage thickening increased more than in the control group. PMID- 4032742 TI - Dual-frame image-freezing unit for two-dimensional echocardiography. Preliminary clinical report. AB - We developed a "dual-frame image-freezing unit", which enables acquisition of two stop-frame images of the two-dimensional echocardiogram at different points within one cardiac cycle. We assessed the clinical usefulness of this unit by estimating the left ventricular ejection fraction with apical biplane two dimensional echocardiography in 25 patients who underwent left ventricular biplane cineangiography. The unit functioned successfully in all instances. It was much easier to obtain the left ventricular end-diastolic and end-systolic echocardiographic images than to obtain such images using conventional videotape play-back. The quality of the images obtained by this unit was better than those obtained from videotape play-back. The echocardiographic estimates of the left ventricular ejection fraction showed an excellent correlation with estimates obtained by contrast left ventricular cineangiography. We conclude that this dual frame image-freezing unit can be satisfactorily applied for the assessment of the left ventricular ejection fraction by two-dimensional echocardiography. PMID- 4032744 TI - Early postoperative echocardiographic studies of atrial septal defects. AB - Fifteen consecutive adult patients with uncomplicated atrial septal defects (ASD) underwent echocardiographic examinations both before and 3-8 days (mean 7 days) after surgery to study the early postoperative changes in cardiac dimensions and interventricular septal motion. Echocardiographic analyses included patterns of interventricular septal motion, right and left ventricular dimensions at end diastole (RVDd & LVDd), aortic root dimension at end-diastole (ARDd) and left atrial dimension at end-systole (LADs). The results showed that the septal motion was abnormal in 87% (13/15) before and 40% (6/15) after operation. RVDd decreased from 36 +/- 7 mm to 27 +/- 7 mm (p less than 0.01) while LVDd increased from 33 +/- 6 mm to 39 +/- 4 mm (p less than 0.01). There were no significant changes in LADs and ARDd after surgery. These observations suggest that in patients with ASD the ventricular dimensions and patterns of interventricular septal motion are changed significantly shortly after surgical repair. PMID- 4032745 TI - Radionuclide imaging for assessment of myocarditis and postmyocarditic state in infant and children. Thallium-201 myocardial imaging and technetium-99m-HSA gated equilibrium ventriculography. AB - T1-201 myocardial imaging and Tc-99m-HSA gated equilibrium ventriculography were performed in 1 infant and 11 children between 2 months old and 12 years old with myocarditis. The time of first evaluation was between 1 week and 13 months after the onset. Their clinical manifestations were congestive heart failure in 2 patients, pericardial effusion in 2 patients, syncope in 1 patient, convulsions in 1 patient and palpitations in 7 patients. Significant elevation of virus antibody titer was demonstrated in 6 patients. A perfusion defect was observed with T1-201 imaging in 9 of 12 patients with myocarditis. A right ventricular image was observed in 5 patients. A reduced LVEF was present in 4 patients and a reduced RVEF was found in 2 patients. Cardiac catheterization was performed in 8 patients and an endomyocardial biopsy was done in 7. The myocardial specimens revealed postmyocarditic pathological changes upon microscopic evaluation. No coronary artery obstructive or stenotic lesions were observed in these patients. T1-201 myocardial imaging is a useful non-invasive technique for evaluating the cardiac performance and myocardial damage in acute myocarditis and the postmyocarditic state. We conclude that T1-201 uptake of myocardium is dependent upon both regional coronary perfusion and the activity of myocardial cells in patients with myocarditis and in the postmyocarditic state. PMID- 4032746 TI - Right ventricular systolic and diastolic function at rest in patients with coronary artery disease. Assessment with equilibrium radionuclide ventriculography. AB - Right ventricular systolic and diastolic function was studied in patients with ischemic heart disease using equilibrium radionuclide ventriculography. In patients with inferior myocardial infarction and proximal right coronary lesions, the right ventricular ejection fraction (0.43 +/- 0.06, n = 10, mean +/- SD) and peak filling rate (1.7 +/- 0.4 EDV/sec) were lower than normals (0.57 +/- 0.07 and 2.7 +/- 0.4 EDV/sec, n = 10, p less than 0.001, respectively). In these patients, the right ventricular time to peak filling rate was longer than in normals (225 +/- 36 msec vs 136 +/- 45 msec, p less than 0.001), while the left ventricular ejection fraction remained normal. In patients with inferior myocardial infarction and distal right coronary lesions, the right ventricular ejection fraction, peak filling rate and time to peak filling rate were not different from those in normals. Even in patients with proximal right coronary lesions, the right ventricular ejection fraction was normal unless they had an inferior myocardial infarction. A decreased left ventricular ejection fraction and abnormal motion of the ventricular septum did not affect the right ventricular ejection fraction. The present results suggest that patients with an inferior myocardial infarction and proximal right coronary lesion often develop right ventricular systolic and diastolic dysfunction. PMID- 4032747 TI - Renal function in children after large dose contrast medium angiocardiography. AB - Serum creatinine and routine urinalysis were obtained and glomerular filtration rate estimated in 56 consecutive and hemodynamically stable children with congenital heart disease undergoing cardiac catheterization and angiocardiography, a day prior to, 1 and 7 days following the procedure. None had a history of renal disease. The patients were divided into 2 groups: Group I, 32 patients who received less than 3 ml/Kg of Renagrafin 60 and Group II, 24 patients who received greater than 3 ml/Kg. Despite a slight rise of creatinine on the first day, there were no statistically significant changes in serum creatinine or glomerular filtration rate for either group following the procedure. Occult blood was present in the urine of 2 in Group I and 1 in Group II prior to cardiac catheterization; this resolved in all cases after the procedure. Three patients in Group I and 1 in Group II developed transient trace proteinuria following the angiographic procedure. It is concluded that in children with congenital heart disease and normal kidney function, substantial doses of standard contrast medium administered during angiocardiography do not produce any apparent impairment of renal function. PMID- 4032748 TI - Intracardiac myxoma. AB - Six intracardiac myxomas and 2 thrombi were subjected to scanning electron microscopy (SEM). Surface morphology of myxomas was distinct from thrombi. The surface of myxoma was either smooth or thrown into projections which had a continuous endothelial lining. This was lacking in thrombi. Cut surface of myxoma revealed the presence of round to polyhedral cells having blunt villi and/or pit like depressions on their surface in a stroma of fibres, granular material and blood vessels. Thrombi were composed of blood elements enmeshed within fibres. No cells of the type encountered in myxomas were present. PMID- 4032749 TI - Long-term survival of cultured adult rat heart cells. AB - This paper reports several modifications of our previous culture method for adult rat heart cells. Mechanical separation of the cells at 12 rpm rather than 8 rpm doubled the number of beating cells in the final culture medium. A 60% Ficoll Paque solution was found to be optimal for exclusion of non-muscle cells such as endothelial cells and fibroblasts from the culture, followed by frequent medium exchange to eliminate traces of this reagent from culture medium. However, the presence of some non-muscle cells seemed to exert a positive effect on culture longevity. Eagle's MEM medium containing 20% FBS resulted in maximum (over 50 days) survival of cultures. PMID- 4032750 TI - Sequence of electrophysiological property and metabolic disorder in ischemic myocardium. AB - The relationships of electrical changes to the time course of reduction in adenosine triphosphate (ATP) content were examined in 41 dogs with coronary artery ligation and 14 control dogs. Twenty dogs with malignant ventricular arrhythmias within 10 min of ischemia (VA dogs) were characterized by widening of the composite electrogram duration (147 +/- 47 msec at 5 min). In contrast, the composite electrogram duration was narrower (71 +/- 12 msec at 5 min, p less than 0.001) in 21 dogs without malignant arrhythmias (non-VA dogs). The degree of ATP reduction in VA dogs was significantly less at 3 min (3.11 +/- 0.28 mumol X g-1, p less than 0.05) and at 5 min (2.93 +/- 0.28 mumol X g-1, p less than 0.05) than in non-VA dogs (2.76 +/- 0.22 mumol X g-1, 2.39 +/- 0.44 mumol X g-1, respectively). The width of the electrograms in VA dogs decreased gradually after 10 min of ischemia, and it was not significantly different from non-VA dogs by 13 min, which coincided with disappearance of a difference in ATP content (2.10 +/- 0.34 mumol X g-1 and 2.35 +/- 0.23 mumol X g-1 in VA dogs and non-VA dogs biopsied at 10-20 min of ischemia). It was concluded that the metabolic deterioration in VA dogs advanced more slowly than that in non-VA dogs within 5 min of ischemia and the decrease in the width of the electrogram after 10 min did not result from a partial recovery of ischemia. PMID- 4032751 TI - [Clinical value of SCC-antigen, a subfraction of tumor antigen TA-4, in the management of cervical cancer]. AB - The present study shows the clinical values of SCC-Antigen, a subfraction of TA 4, for the management of squamous cell carcinoma. Serum SCC-Antigen levels of 2.0 ng/ml was designated as the cut-off value. Serum antigen levels were positive in 53.5% of cervical squamous cell carcinoma, and the changes in serum antigen levels reflected the disease progress. The antigen was also positive in cancer of vagina, vulva, lung or esophagus. To detect the early cervical cancer, flow cytometric analysis of the exfoliative cells was conducted, using anti-TA-4 serum, which was found to be particularly useful for the detection of early disease. It was concluded that the use of SCC-Antigen would be promising in clinical care. PMID- 4032752 TI - [CO2 laser in treating head and neck cancer]. AB - CO2 laser is especially useful in treating cancer of tube- and cavity-organs. For carcinomas of the tongue, we have employed three types of laser usage. Carcinomas confined within the mucosa are treated by laser alone. For carcinomas invading the muscle to some extent, we make a mass reduction surgery by means of laser which is followed by (chemo)radiotherapy. Carcinomas with extensive muscular invasion are first treated with induction chemotherapy. If the chemotherapy is effective, we add laser surgery for the purpose of mass reduction and chemoradiotherapy follows. 26 patients were treated and none has developed local recurrence. For glottic carcinomas, we have applied laser in two ways: laser surgery alone and laser combined with (chemo)radiotherapy. We have treated 58 patients with glottic carcinoma. 14 developed local recurrence. Of these 14, 13 were successfully treated but the other died because he refused to have further treatment. PMID- 4032753 TI - [Treatment of neoplasms of the uterine cervix by CO2 laser]. AB - CO2 evaporation was undertaken on 241 patients with cervical intraepithelial neoplasia. The results obtained six weeks after the treatment revealed disappearance of 89.6% of the lesions, and the therapeutic results obtained one year after reirradiation were favorable; 97.5% of the lesions had disappeared. However, not a few patients have some neoplasms of the uterine cervix to which this therapy is not applicable. Therefore, conization was started for treatment combined with diagnosis by means of CO2 laser. The therapeutic effect has been studied in 64 patients to date. Five patients with carcinoma of stage Ia and four patients with endoepithelial carcinoma who had undergone hysterectomy after conization were examined for the presence or absence of residual lesions. The lesions had disappeared completely. The remaining 64 patients who had not undergone hysterectomy are now under follow-up study, and a residual lesion was observed in only one patient, suggesting the possibility of treating a large number of CIN patients by evaporation combined with conization. PMID- 4032754 TI - [Photodynamic therapy of superficial tumors and carcinoma in situ of the bladder]. AB - Photodynamic therapy (PDT), in which hematoporphyrin derivative is activated by an argon-dye laser, was performed on 36 superficial tumors using a 400 micron quartz fiber and cystoscope (spot PDT), and also carried out in 7 patients with primary or secondary CIS, 9 patients with secondary CIS associated with TaTl tumors and 2 patients with multiple small tumors, using a motor-driven laser light scattering optic automatically controlled by a computer (total PDT). In spot PDT, for tumors up to 2 cm in size the light intensity should be 300 mW/cm2 for 5 to 10 minutes or more. For the CIS therapy, the light dose used was 10 to 30 Joules/cm2. There has been no recurrence at present in 8 of the 18 patients at a mean follow-up period of 6.6 months. The techniques and problems associated with total PDT are reported. PMID- 4032755 TI - [590-S]. AB - 590-S (1-phthalidyl-5-fluorouracil) is a derivative of 5-fluorouracil and shows a several characteristics in experimental studies. That is, good absorption from the intestine, high blood levels of 5-fluorouracil, its rapid clearance, low toxicities, excellent tumor inhibition and broad anticancer spectrum, etc. From preliminary studies and phase I studies, MTD is thought to be 750-800 mg/m2 in daily administration. Mild G.I. toxicities was encountered in a few cases. However, CNS toxicities were not experienced in any of our cases. PMID- 4032756 TI - [SM-108]. AB - The purpose of this paper is to analyze the available data on SM-108 (4 carbamoylimidazolium 5-olate) with respect to its clinical usefulness, optimal method of administration, and side effects. Successful remission induction was achieved in atypical leukemia using low dose SM-108. To analyze the action of SM 108, freshly isolated leukemic cells and cells from human leukemic cell line were cultured in the presence of SM-108. Minimal evidence of differentiation induction was observed. SM-108 in a higher dose, alone or in combination with other drugs was advocated for the treatment of adult ALL. Side effect including myelotoxicity and gastrointestinal toxicity was minimal. PMID- 4032757 TI - [The role of radiation therapy of diffuse large cell lymphoma localized in the head and neck]. AB - Eighty-one patients with diffuse large cell lymphoma localized in the head and neck were treated with radiation between 1971 and 1981. Of these, 52 had Waldeyer's ring disease, 14 nodal, and 15 extranodal disease. Overall survival and relapse-free survival rates at five years after radiation therapy alone were 69% and 52%, respectively. Five-year disease-free rates of patients with Waldeyer's ring disease were 91% in stage I, and 71% in stage II, which are much better than those of other extranodal and nodal diseases. According to mass size, the five-year relapse-free rate for the small-mass less than 5 cm in diameter group was much better (72%) than that for the large-mass group (29%). PMID- 4032758 TI - [The f-factor (fat infiltration) in breast cancer as a new indicator for predicting the occurrence of bone metastasis]. AB - The correlation between tumor infiltration into extramammary fatty tissues (f factor) and bone metastasis was retrospectively analyzed in 117 patients with breast cancer. Five (10.6%) and 26 (37.1%) patients developed bone metastases among 47 f-negative and 70 f-positive subjects, respectively, and the frequency of bone metastasis was significantly higher in the f-positive than in the f negative group (p less than 0.005). Furthermore, bone metastasis was more frequent in the f-positive than in the f-negative group among patients of the same stages, lymph node involvements, or histological types. The f-factor was suggested to be a new indicator for predicting the occurrence of bone metastasis in breast cancer. PMID- 4032759 TI - [Clinicopathological study of a malignant lesion in the remnant stomach]. AB - Thirty-six cases of malignant lesion in the remnant stomach were studied clinicopathologically. Ten had been surgically managed as benign lesions and eight were suspected of being metachronous multiple gastric cancer. The pathological characteristics of the malignant lesions and the operation interval (mostly more than 10 years) were similar in these two groups. Although malignant lesion in the remnant stomach is difficult to differentiate clearly when there is no sufficient histological evidence, the operation interval of more than 10 years can be one of the criteria for differential diagnosis. PMID- 4032760 TI - [Histogenesis of metaplastic and cancerous changes in the gallbladder]. AB - Six hundred cases of resected gallbladder were histologically investigated by serial sections for intestinal (goblet cell) metaplasia and pseudopyloric gland metaplasia. Intestinal metaplasia was found at the rates of 4.8% and 30.0% in the stone-free cases and those with bile duct stone, respectively. It was found at rates of 52.0% in cases of gallbladder carcinoma. On the other hand, goblet cell like cells were found at the rates of 35.0% and 26.0% in the tissues of carcinoma and dysplasia, respectively. Although the normal epithelium of the gallbladder has sulfomucin, goblet cells contain sialomucin. The ratio of sialomucin containing cells increased in dysplasia and carcinoma. Pseudopyloric gland metaplasia was found at the rates of 46.0 and 70.0% in the stone-free cases and those with bile duct stone, respectively. However, it should be considered that this change has less of a relationship with the bases of carcinogenesis than with those of intestinal metaplasia. PMID- 4032761 TI - [Radioprotective effect of local hypothermia]. AB - We attempted local hypothermia to prevent radiation dermatitis and stomatitis. With regard to parasternal skin reactions postoperatively irradiated breast cancer, dry and moist desquamation, which occasionally occurred with conventional irradiation was not observed in combination with local cooling. As for head and neck tumors, patients who complained of stomatitis decreased with the local cooling, and no one wanted a pause in irradiation before 40 Gy. As local hypothermia is free from danger and does not require special equipment, it was considered to be widely applicable. PMID- 4032762 TI - [A case of polymorphous adenocarcinoma in the right parotid gland]. AB - The nature of adenocarcinomas of parotid gland origin seems to be still unclear because of the rarity of this lesion. A 65-year-old man with a "polymorphous adenocarcinoma" of the parotid gland is presented. This tumor is characterized by a marked diversity in the histologic manifestations, presenting dominantly solid, tubular, pseudoadenoid cystic sarcomatoid patterns. The tumor cells showed distinctive signs of high grade malignancy such as the occurrence of mitotic figures and involvements of lymphatic vessels and/or blood vessels. "Polymorphous adenocarcinoma" is a histologically distinctive neoplasm unlike other adenocarcinomas of parotid gland origin. PMID- 4032763 TI - [A case of focal carcinoma of the stomach found eight years after diagnosis of atypical epithelium]. AB - An 80-year-old man showed depressive change (IIc-like lesion) in the aggregated lesion of hemisphere nodules about eight years after diagnosis of atypical epithelium in the lesser curvature of the stomach. Carcinoma was strongly suspected by the biopsy specimen from the depressive lesion. In the resected specimen, carcinoma was present in the depressive lesion. It is sometimes difficult to distinguish atypical epithelium from carcinoma by endoscopic findings and biopsy specimens. So, in addition to being alert to gross changes of the lesion, it is very important to obtain biopsy specimens with a view to morphological changes of the lesion. PMID- 4032764 TI - [Solid and cystic tumor of the pancreas--report of a case in a 13-year-old girl]. AB - A case of adenocarcinoma of the body of the pancreas in a 13-year-old girl is reported. The gross appearance of the tumor revealed apparent encapsulation, cystic degeneration and hemorrhagic necrosis. Microscopically, the tumor resembled an islet cell tumor, but immunohistochemically there was no evidence of endocrinic activities. Ultrastructurally, tumor cells contain numerous mitochondria but no secretory or zymogen granules. This peculiar type of tumor usually arises in young women and shows a favorable prognosis. Diagnosis should be established immunohistochemically and ultrastructurally. PMID- 4032765 TI - [A case report of early rectal carcinoma, IIa + IIc type, with no invasion of the submucosa]. AB - A 66-year-old woman was admitted to the Hakodate Chuo Hospital because of abdominal discomfort. A barium enema study revealed a deformity of the middle Houston's valve of the rectum and granular lesions at the Rb region of the rectum. A colonoscopic examination showed the IIa + IIc type of early rectal carcinoma. A resected specimen also revealed IIa + IIc type early rectal carcinoma, 8 X 13 mm in diameter, and well-differentiated adenocarcinoma with no invasion of the submucosa. Infiltration into the lymphatic vessels and regional lymph node metastasis were not encountered. The deformity of the rectal Houston's valve was checked by a barium enema study. It should be emphasized that early detection of colorectal carcinoma with no invasion of the submucosa, requires careful barium enema studies and colonoscopic examination. PMID- 4032766 TI - [A case of multilocular renal cyst showing neoplastic features]. AB - A 45-year-old woman was hospitalized with complaint of upper right abdominal pain. By serial examination, it was difficult to distinguish renal cyst from renal cancer. But, because of the frequency of the attacks of upper abdominal pain, nephrectomy was undertaken. The tumor measured 5 X 5 X 3 cm, was distinct from normal renal tissue, and consisted of a small cyst. Histologically, we diagnosed a multilocular renal cyst, and its lining cells showed small atypia and adenomatous proliferation. We concluded that this multilocular renal cyst showed neoplastic features. PMID- 4032767 TI - [Two cases of paragangliomas of the cauda equina--case reports and review of the literature]. AB - Paragangliomas are tumors arising in the paraganglia and rarely occurring in the cauda equina. We report two cases of paraganglioma arising in this region. The tumors exhibited a typical "Zellballen" pattern, and immunohistochemical studies were positive for neuron-specific enolase, but negative for S-100 protein and glial fibrillary acidic protein. Electron microscopic studies confirmed electron dense neurosecretory types of granules in the tumor cells. Only 23 cases of paragangliomas in this region have been previously reported. A brief review of the literature is included. PMID- 4032768 TI - [Reconstruction of oral defects using free revascularized jejunum transfer]. AB - Reconstruction of the oral cavity after extended surgery poses many difficult problems. The vital functions of the oral cavity, especially swallowing, mastication and breathing, are seriously impaired by resection of the tongue, floor of the mouth, gingiva or jaw bone. We have used the free revascularized jejunal transfer for reconstruction of the oral cavity in 10 patients and have had good functional and cosmetic results. The advantages of this method are as follows: 1) it is a one-stage operation; 2) the flexibility of the graft preserves maximal tongue function; 3) the graft can be applied to difficult anatomic sites, and 4) the mucosal defect is covered with jejunal mucosa and induration is minimum. Our success rate with this procedure has been 90%. In our experience, this transfer is useful for reconstruction of a massive defect in the oral cavity. PMID- 4032769 TI - [The measurement of SCC antigen in squamous cell carcinoma of the lung]. AB - Serum squamous cell carcinoma (SCC) antigen levels were measured in 55 patients with lung cancer, 43 with benign diseases and 50 normal subjects. At the same time, carcinoembryonic antigen (CEA) was measured for comparison. The mean SCC antigen levels were 1.47 + 0.50 ng/ml in 50 normal subjects. The percentage of positive case for SCC antigen (higher than 2.6 ng/ml) was 27.8% in lung cancer as a whole, 17.6% in adenocarcinoma, 47.6% in squamous cell carcinoma, 6.7% in small cell carcinoma and none in large cell carcinoma. Fifty percent of the Stage II patients were positive for SCC antigen, and the assay might be a possibility for early diagnosis. Our study suggests that SCC antigen assay may be a useful test for the identification and evaluation of lung cancer patients. PMID- 4032770 TI - [Clinical study of the measurement of tissue polypeptide antigen in patients with breast cancer]. AB - Tissue polypeptide antigen (TPA) concentrations in patients with breast cancer were measured using a radioimmunoassay (RIA) kit. Although this RIA kit presented some problems in the dilution test of high-concentration samples, it was found to be adequate for clinical use. It was shown that the measurement of serum TPA concentration was useful in monitoring the local recurrence, for the early diagnosis of distant metastasis and for evaluating the therapeutical effect after surgery. TPA concentration showed no correlation with CEA concentration. Therefore, in order to raise the rate of diagnostic success, simultaneous measurement of both TPA and CEA was essential. PMID- 4032771 TI - [Pelvic lymph node metastasis of cervical adenocarcinoma and adenosquamous carcinoma]. AB - Thirty-one cervical cancers, comprised of 16 adenocarcinomas and 15 adenosquamous carcinomas, were clinicopathologically examined to demonstrate the characteristic features of pelvic lymph node metastasis. The average number of metastatic nodes in each case was 2.6. The most common loci of metastases were the nodi lymphatici obturatorii, iliaci externi and ligamenti cardinales. The histologic distributions in the metastatic nodes suggested that the adenocarcinoma element was more likely to metastasize to the nodes than its squamous counterpart. PMID- 4032772 TI - [Ultrastructural studies of central-type early squamous cell carcinoma of the lung]. AB - Characteristics of the nuclei in histopathologic preparations obtained from a patient with bronchial carcinoma and two patients with microinvasive bronchial carcinoma were studied by transmission electron microscopy. In carcinoma in situ, the nuclei showed slight or moderate irregularity in the nuclear outline. The number of perichromatin granules was usually one to 10 per nucleus section. Formation of fibrillar centers was not marked. In microinvasive carcinoma, the nuclei were more irregular in nuclear outline than in carcinoma in situ. The number of perichromatin granule was usually more than 11 per nucleus section. Formation of fibrillar centers was predominant. PMID- 4032773 TI - [An autopsy case of malignant mesenchymoma of the diaphragm]. AB - An autopsy case of a huge tumor in the right thorax is reported. A 71-year-old man complained of dyspnea and died after three months of hospitalization. The tumor, consisting of a circumscribed mass measuring 24 X 24 X 8 cm and weight 3.7 kg, originated from the right diaphragm and had no metastasis. Histologically, the tumor comprised multiple mesenchymal elements of fibrosarcoma, rhabdomyosarcoma, osteosarcoma and chondrosarcoma, and there was no distinct border between these different components. This tumor fulfills the criterion of malignant mesenchymoma (Stout). The histogenesis of the tumor is discussed with a survey of literature. PMID- 4032774 TI - [A case of breast cancer with lipid secretion]. AB - Lipid-secreting carcinoma of the mammary gland is a very rare disease entity. We have experienced a 59-year-old woman diagnosed as having cancer of the left breast and treated by mastectomy. The excised material was found to be afflicted with common duct carcinoma partially involved in lipid secretion. This patient had a relapse and died three and a half years after the mastectomy. The autopsy material consisted mostly of lipid-secreting carcinoma. The pathogenesis of this disease and changes of histological figures are also discussed. PMID- 4032775 TI - [Ganglioneuromatosis with carcinoid foci in the large bowel]. AB - A rare case of a 27-year-old man who suffered from ganglioneuromatosis with five carcinoid foci arising from the colon and underwent subtotal colectomy is reported. There was no malignancy. The tumors extended to the mucosa and/or submucosa, and in most parts, tumors created polypoid lesions protruding into the intestinal lumen. In the rectum the tumors showed circumscribed extension around the wall. In the sigmoid and descending colon, polypoid lesions were seen on the side opposite from the attachment line of the mesocolon. In one of five carcinoid foci, a transitional pattern between carcinoid and neuroma was investigated. PMID- 4032776 TI - [Correlation between lymphangiography and abdominal computed tomography in the diagnosis of malignant lymphoma of the retroperitoneal lymph nodes]. PMID- 4032777 TI - [Studies on platelet derived leukocyte activating substances. (1). Platelet derived granulocyte aggregating factor]. PMID- 4032778 TI - [Relationship between prognosis and CFU-C-derived colony formation in patients with aplastic anemia]. PMID- 4032779 TI - [Studies on anti-erythrocyte antibodies contained in heat-treated human plasma protein, albumin and immunoglobulin preparations--their possible influences on hemolysis in burn patients and in the pretransfusion cross match test]. PMID- 4032780 TI - [Recent trends of biomembranology]. PMID- 4032781 TI - [Application of cytological engineering to the field of membrane physiology]. PMID- 4032782 TI - [Study of biomembrane with electron microscopy]. PMID- 4032783 TI - [Application of NMR in the study of cell membrane]. PMID- 4032784 TI - [Thermodynamics of membrane transport]. PMID- 4032785 TI - [Receptor-mediated endocytosis and the structure of membrane receptors]. PMID- 4032786 TI - [Pathomembranology and concept of membrane diseases]. PMID- 4032787 TI - [Abnormal membrane transport in brush border disease. a. Re-absorption problem in the kidney tubules]. PMID- 4032788 TI - [Abnormal membrane transport in brush border disease. b. Intestinal absorption disorders]. PMID- 4032789 TI - [Abnormal LDL receptor, hyperlipemia and arteriosclerosis]. PMID- 4032790 TI - [Abnormal cell membrane and muscle cell differentiation disorder in muscular dystrophy]. PMID- 4032791 TI - [Blood cell membrane abnormality]. PMID- 4032792 TI - [Radionuclide imaging with labeled monoclonal antibody]. PMID- 4032793 TI - [Community care of hypertension]. PMID- 4032794 TI - [Problems in the management of mild hypertensive patients following MRFIT]. PMID- 4032795 TI - [Sodium and proteins in diet therapy of hypertension]. PMID- 4032796 TI - [Non-invasive evaluation of the viability of the myocardium in heart preservation. An experimental study]. PMID- 4032797 TI - [Pharmacology of calcium channel blockers]. PMID- 4032798 TI - [Antihypertensive diuretic agents]. PMID- 4032799 TI - [Arachidonic acids]. PMID- 4032800 TI - [Acinetobacter calcoaceticus infection--bacteriological and clinical studies of septicemia]. PMID- 4032802 TI - [Development of a new chromogenic Limulus test specific to endotoxin]. PMID- 4032801 TI - [Legionella pneumophila infection. Studies on the host defense mechanism to aerosol challenge with L. pneumophila]. PMID- 4032803 TI - [Determination of chymotrypsin in stools with a new kit]. PMID- 4032804 TI - [The levels of fibrinopeptide A and fibrinopeptide B beta in the urine from patients with chronic glomerulonephritis during urokinase therapy]. PMID- 4032805 TI - [Investigation of the aging phenomena in the eye (lens) by atomic absorption spectrophotometry--high performance aqueous gel permeation chromatography]. PMID- 4032807 TI - [Light microscopic characteristics of mucosal and connective tissue mast cells of the respiratory and gastro-intestinal tracts]. PMID- 4032806 TI - [Studies on the condition of human lymphocyte blast transformation by PHA]. PMID- 4032808 TI - [Adenosquamous cell carcinoma of the gastrointestinal tract--I. The stomach]. PMID- 4032810 TI - [Study of early gastric cancer less than 1 cm in diameter]. PMID- 4032809 TI - [Imaging diagnosis of biliary cystadenoma and cystadenocarcinoma]. PMID- 4032811 TI - [CT findings of Crohn's disease of the small intestine]. PMID- 4032812 TI - [Radiation therapy for metastatic brain tumors]. PMID- 4032813 TI - [Delineation of target volume on CT images with esophageal carcinoma]. PMID- 4032814 TI - [Recent radiobiological development for daily multiple fractionations]. PMID- 4032815 TI - [Aortic arch aneurysm]. PMID- 4032816 TI - [Bone scintigraphy of the maxillofacial fibro-osseous lesion]. PMID- 4032817 TI - [Multiple aneurysms on the horizontal portion of the anterior cerebral artery (A 1)]. PMID- 4032818 TI - [A case of multiple epidural metastases of neuroblastoma]. PMID- 4032819 TI - [A case of hypertrophic pachymeningitis]. PMID- 4032820 TI - [A case of cholecystocolic fistula demonstrated with 99mTc-PMT imaging]. PMID- 4032821 TI - [A case of cavernous lymphangioma of the spleen]. PMID- 4032822 TI - [Intra-arterial infusion of SNP for peripheral ischemia caused by acute ergotism]. PMID- 4032823 TI - [Evaluation of the influence of ambient temperature and humidity on the hydration level of the stratum corneum]. PMID- 4032824 TI - [A study on quick diagnosis during surgery of malignant melanoma with the touch fluorescence method]. PMID- 4032825 TI - [Histological and electron microscopic studies on cutaneous amyloid deposition in NC mice]. PMID- 4032826 TI - [Favre-Racouchot syndrome (elasteidose cutanee nodulaire a kystes et a comedons)- father and son and its hereditary pathogenesis]. PMID- 4032827 TI - [Report of siblings with xeroderma pigmentosum, genetic complementation group D]. PMID- 4032828 TI - Induction of macrophage growth by lipoprotein. AB - Cell-free tumorous ascitic fluid stimulated growth of variously induced mouse peritoneal macrophages and resident macrophages in vitro. This induction of macrophage growth by the tumorous ascitic fluid was confirmed by autoradiography. The macrophage growth-stimulating activity was stable on heating at 100 degrees C, in contrast to that of macrophage growth factor (colony stimulating factor) previously reported. This heat-stable macrophage growth-stimulating activity was recovered in the lipoprotein fraction of tumorous ascitic fluid. The lipoprotein from heat-treated normal mouse serum also induced growth of macrophages. These results indicate that lipoprotein can induce macrophage proliferation, at least in vitro. PMID- 4032829 TI - Compositional changes in brain lipids, especially cerebroside and gangliosides, of rats treated with methylmercury chloride. AB - Rats were orally given 4 mg of methylmercury chloride per kg per day up to 14 days, and killed at 4-day or arbitrary intervals. Parietal gray matter and cerebellum were taken for lipid analyses. The ganglioside content increased during the early stage before the manifestation of clinical symptoms. After the onset of clinical signs, the total lipid concentration was elevated, and especially the levels of phosphatidylethanolamine and cerebroside were increased. The ganglioside distribution patterns were also altered in the late stage, showing decreased proportion of GD1a and increased percentages of GD1b and GQ1b. PMID- 4032830 TI - [Sequential histochemical studies of the esophageal carcinoma in rats induced by N-methyl-N-amylnitrosamine]. PMID- 4032831 TI - [A study on reflux esophagitis in progressive systemic sclerosis (PSS): second report. Nocturnal gastroesophageal motility and esophageal pH in supine position]. PMID- 4032832 TI - [Quantitative study on macromolecular glycoprotein in gastric mucosa]. PMID- 4032833 TI - [The effects of gastrointestinal hormones on the growth and protein synthesis of human stomach and colon carcinomas]. PMID- 4032834 TI - [Clinical significance of the determination of serum bile acid and oral bile acid loading test in gastrointestinal diseases]. PMID- 4032835 TI - [A case of the long-term infection of Isospora belli]. PMID- 4032836 TI - [A case of primary biliary cirrhosis complicated with CRST syndrome]. PMID- 4032838 TI - [The changes in gangliosides in the liver and serum in hepatectomized rats]. PMID- 4032837 TI - [A case of idiopathic portal hypertension with a splenic arterial aneurysm and severe deposits of iron salts in the spleen]. PMID- 4032839 TI - [A case of nail-patella syndrome presenting a steroid-resistant nephrotic syndrome--in reference to clinical and morphologic study]. PMID- 4032840 TI - [An experimental pathological study on the ischemic kidney induced in rabbits by constriction of the homolateral renal artery]. PMID- 4032841 TI - [Clinicopathological study of idiopathic membranous nephropathy--long-term follow up study]. PMID- 4032842 TI - [Pregnancy in patients with minimal change nephrotic syndrome]. PMID- 4032844 TI - [The effect of antigenic charge on the glomerular deposition of immune complexes in acute serum sickness of rabbits]. PMID- 4032843 TI - [Immunopathological examinations in experimental interstitial nephritis in goats]. PMID- 4032845 TI - [Vanadium retention and its possible toxic effects on membrane transport in uremic patients]. PMID- 4032846 TI - [Erythrocyte Na/K flux ratio in hypertensive and renal failure patients]. PMID- 4032847 TI - [Arrhythmias in uremic patients on maintenance hemodialysis studied with 24-hour electrocardiographic recording]. PMID- 4032848 TI - [Pseudo-Bartter's syndrome and surreptitious abuse of furosemide in a woman complicated with masked idiopathic edema and defective character]. PMID- 4032850 TI - [Clinical studies on acute renal failure]. PMID- 4032849 TI - [A case of familial IgA nephropathy]. PMID- 4032851 TI - [Detection and evaluation of left atrial myxoma by gated radionuclide imaging]. PMID- 4032852 TI - [Clinical application of NMR-CT (report 6)--clinical utility of NMR-CT for uterine disease]. PMID- 4032853 TI - [Development of a new Xe-133 single dose multi-step method (SDMM) for muscle blood flow measurement using a gamma camera--methodology and basic evaluation]. PMID- 4032854 TI - Evidence for in vivo effect of lithium on p-aminohippurate transport in rat kidney, preliminary study. AB - We examined the effect of lithium on rat renal handling of p-aminohippurate (PAH) and accumulation of organic ions by rat kidney cortical slices. When infused intravenously with lithium at the rate of 0.13 mmoles/kg/min, decreased renal clearance of PAH as well as no significant changes in glomerular filtration rate and plasma PAH level was observed at the first clearance period during lithium infusion. As we expected, tubular secretion of PAH also was decreased significantly by the infusion of lithium. Therefore, it is suggested that the decrease in the clearance of PAH was due to the decrease in the tubular secretion of PAH. After four days of injections with lithium (4 mmoles/kg, i.p., once a day), a significant decrease in PAH accumulation in the slices was detected. No inhibition of tetraethylammonium accumulation was observed. Lithium pretreatment did not alter water content and extracellular space of the slices. The results suggest that lithium selectively inhibits the organic anion transport system in kidney with the in vivo treatment and follows our previous work in which we showed the in vitro effect of lithium on organic anion accumulation in the slices. PMID- 4032855 TI - Comparisons between discrete lever-press and shuttle avoidance responses in mice: acquisition processes and effects of psychoactive drugs. AB - Acquisition processes of discrete lever-press (L-type) and shuttle (S-type) avoidance responses as well as effects of psychoactive drugs thereon were investigated in dd strain mice. The mice showed a more rapid acquisition of S type avoidance than L-type. However, the mean avoidance rates and occurrences of good-performing mice (showing an avoidance rate of higher than 75%) were almost the same in both types when the training was carried out for more than 15 sessions of 1 hr each. The response rate of L-type avoidance was 2.5-3 times as high as that of S-type avoidance. Methamphetamine and cocaine increased the response rate in almost the same grade in both types of avoidance. Chlorpromazine, haloperidol, pilocarpine and physostigmine suppressed both L-type and S-type avoidance responses. However, the L-type showed a higher sensitivity than the S-type to the avoidance-suppressing effect of these drugs. Atropine, scopolamine and morphine suppressed L-type avoidance response, while they facilitated S-type avoidance. The drug-induced changes in the response rate of the S-type were well correlated with those in the ambulatory activity. The changes in the response rate of the L-type were also consistent with those in the ambulatory activity after administration of methamphetamine, cocaine, chlorpromazine, haloperidol, pilocarpine and physostigmine, but inconsistent after atropine, scopolamine and morphine. The present results suggest that L-type and S-type avoidance responses in mice sometimes show a different change after administration of psychoactive drugs. PMID- 4032857 TI - Sodium salicylate activates cathepsin B but not cathepsin H from rat spleen. AB - Effect of sodium salicylate (SA) and its analogues on lysosomal cysteine proteinases, cathepsins B and H, was investigated. Using a sensitive fluorometric assay, SA was shown to activate cathepsin B but not cathepsin H in the presence of cysteine. Kinetics data showed that the SA-stimulated reaction was due to a 4.5-fold decrease in Km. SA caused a decrease in the inactivation rate of cathepsin B by leupeptin and E-64. It was suggested that SA stimulates the activation process of the essential cysteine residue. PMID- 4032856 TI - Effects of prolonged treatment with compound 48/80 on the gastric mucosa and mast cells in the rat. AB - Effects of prolonged administration of compound 48/80 (48/80) on the gastric mucosa, serotonin and histamine levels in serum, and mast cells of rats were studied. Daily administration of 48/80 (0.75 mg/kg, i.p.) for 2 or 4 days produced widespread gastric lesions. Further administration of the agent for up to 12 days did not aggravate the lesions which had developed in the early period of administration of the drug. There were only a few visible lesions and numerous healed ones. Almost the same phenomenon was observed with the daily administration of serotonin plus histamine (10 mg/kg each, i.p.) for 2 to 12 days. While 48/80 given for 2 or 4 days increased serotonin and histamine levels in serum, it induced no appreciable increase of these amines after 8 or 12 days of treatment. Serotonin and histamine levels in peritoneal mast cells significantly decreased after the treatment with 48/80 over a 4 day period. The decrease in gastric lesions after prolonged treatment with 48/80 is due to both the depletion of serotonin and histamine from mast cells and an increased resistance of the gastric mucosa with healed lesions. PMID- 4032858 TI - Effects of various agents on prednisolone-induced gastric lesions in rats. AB - We studied the effects of various agents on prednisolone-induced gastric lesions in rats. Gastric lesions were produced by subcutaneous administration of 50 mg/kg of prednisolone once daily for 4 days to non-fasted rats. Daily oral administration of antipeptic, antisecretory agents and 16-dmPGE2 significantly inhibited the lesions. Antacids and PGI2 had little or not effect. These results suggest that the concomitant use of the above agents with steroid therapy to provide protection of the gastric mucosa warrants further attention. PMID- 4032860 TI - Effects of methamphetamine on dopamine cells in the substantia nigra pars compacta and the ventral tegmental area. AB - The ability of methamphetamine to inhibit the firing rate of dopamine cells in the substantia nigra pars compacta (SNC) and the ventral tegmental area (VTA) was studied. Methamphetamine reduced the firing rates of the dopamine cells in a dose dependent manner in the SNC and the VTA. The doses of methamphetamine required to produce a 50% inhibition of firing rate in the SNC and the VTA were 0.37 mg/kg and 0.28 mg/kg, respectively. PMID- 4032859 TI - Gastric antral ulcers induced by a combination of acid, indomethacin and ischemia in rats. AB - Gastric antral lesions were produced with hemorrhages by vascular ligation induced ischemia in the prepyloric regions in rats. Additional treatments with intraluminal acid application and indomethacin markedly aggravated the lesions. Histological examination showed that the incidence of ulcers which penetrated the muscularis mucosae was nearly 100% upon treatment with a combination of acid, indomethacin and ischemia. This model provides a useful tool for studying gastric ulcer etiology. PMID- 4032861 TI - Five-year clinical evaluation of the St. Jude Medical valve prosthesis in 136 patients. AB - One hundred and thirty-six patients (June 1979, through May 1984) underwent mitral, aortic or double valve replacement and apico-aortic bypass with the St. Jude Medical (SJM) prosthesis, at Ryukyu University Hospital, Okinawa. Operative mortality for the entire group was 4.4 per cent. Late mortality from 1979-1984 was 6.1 per cent. There were no deaths related to mechanical failure. Warfarin anticoagulation was recommended for all patients. The incidence of thromboembolism was 0.76/100 patient years. Post operative catheterization studies in 21 patients one year after operation showed a satisfactory recovery of cardiac function. The SJM valve seems to be the satisfactory artificial valve in present use. PMID- 4032863 TI - Improved results of surgery for esophageal carcinoma in 148 patients. AB - Since the late 1970's, there has been a remarkable decrease in the mortality of patients with esophageal cancer. Factors such as progress in pre- and post operative management, operative technique, and anesthesia all play a contributory role in this improvement. Among 251 Japanese patients with esophageal carcinoma who underwent esophageal resection and reconstruction in our department of surgery since 1965, those treated from 1965-74 and others treated from 1975-1984 were investigated in detail. It became clear that pulmonary complications and anastomotic leakage were the two major complications related to operative mortality. The former has decreased by intensive postoperative care with strong emphasis on cough dynamics, and the latter because of the long gastric tube we devised and which has a good blood supply. These positive events make feasible early postoperative irradiation and cancer chemotherapy. PMID- 4032862 TI - Aneurysms of the descending aorta: surgical experience with three methods of adjunct procedures. AB - Thirteen patients were surgically treated for the repair of aneurysms of the descending aorta, using three different types of adjunct procedures--an external temporary bypass with a vascular prosthesis, a tridodecylmethylammonium chloride (TDMAC) or a partial cardiopulmonary bypass. There was no operative death, though one patient died 73 days following surgery. Significant intraoperative morbidity occurred in 3 patients: one had ventricular fibrillation and the other two massive hemorrhages. There was no instance of paraplegia or renal failure. The only significant complication that developed was pulmonary insufficiency in two patients with a pump bypass. The mean operative time and the mean aortic occlusion time in patients with the TDMAC shunt were shorter than the times in patients with the vascular prosthetic shunt or the pump bypass. TDMAC shunt required no special equipment and cannulation was simpler and safer. PMID- 4032864 TI - Drill needle biopsy for breast cancer. AB - From 1977 to 1983 we have used electric drill needle biopsy of suspicious masses in the breast in 437 patients. In 104 patients with primary breast carcinoma 94 were diagnosed correctly by the initial biopsy, 9 were found on the second or third biopsy and one on the subsequent excisional biopsy. The rate of accuracy of the initial biopsy was 90.4 per cent. The diameters of the 104 carcinomas were less than 2 cm in 62 (59.6 per cent), 2-5 cm in 39 (37.5 per cent) and 5 cm or more in 3 (2.9 per cent). There were 17 patients (16.3 per cent) with a tumor 10 mm or less in diameter. Three hundred and thirty three patients had benign lesions. This drill needle biopsy method can be performed easily and accurately on nodules less than 2 cm, or even 10 mm or less nodules. For a diagnosis of early breast carcinoma made in the outpatient clinic or in screening examination programs, this method may be the most appropriate. PMID- 4032865 TI - Typhoid enteric perforations. AB - Forty-five cases of typhoid enteric perforation are presented. The disease was most common in young males. Half of the perforations occurred during the second week of fever. Diagnosis was mainly clinical, supplemented by radiological evidence of pneumoperitoneum and confirmed at laparotomy by the presence of perforations in the terminal ileum. Laboratory investigations including Widal perforations in the terminal ileum. Laboratory investigations including Widal test and blood culture were of little value. All the 45 were managed operatively by simple closure of the perforation(s) and drainage of the peritoneal cavity. Burst abdomen occurred in 9 per cent and fecal fistula in 20 per cent. Overall mortality was 11 per cent--much lower than that reported in the literature in case of management of typhoid enteric perforations. PMID- 4032866 TI - Basal cell carcinoma with lung metastasis. AB - A forty-seven year-old man had a small ulceration on his left cheek. The ulcer had a repeated crust formation following removal, for ten years. The patient found a hard tumor in the deep site of the ulcer and the tumor was resected. The pathological diagnosis was basal cell carcinoma. The metastases to the regional lymph nodes developed one year later and these lymph nodes were resected. The histological picture was the same as seen in the primary tumor. Lung metastasis occurred three years later. The tumor was resected and the pathological diagnosis was basal cell carcinoma. Multiple lung metastases developed one year later and massive hemoptysis led to a sudden death two years after the thoracotomy. Thirty seven cases of basal cell carcinoma with lung metastases were reported in the literature. This case is the thirty-eighth case and the third occurrence in a Japanese. PMID- 4032868 TI - Rectoanal pressures and rectal compliance in children with rectal prolapse. AB - The results of anorectal manometry in 11 children with complete rectal prolapse were evaluated. Abnormalities of sphincter control or bowel movements occurred in 8 out of these 11 patients. Anal canal pressure of the patients was lower than in the controls, but there was no significant difference of resting pressure profiles of the anorectum between the patients and the controls. Rectoanal reflex was present in all the patients and in the controls. Rectal compliance was significantly lower in the patients, but there was no correlation between rectal compliance and sphincter control of the patients. PMID- 4032869 TI - A lateral approach to below knee amputation. AB - A lateral approach for below knee amputation, with excision of a segment of the fibula and preliminary division of the tendocalcaneous led to a better exposure of all compartments of the leg. PMID- 4032867 TI - Benign mediastinal teratoma associated with Klinefelter's syndrome. AB - We treated a patient with a benign mediastinal teratoma associated with Klinefelter's syndrome which was first thought to be a malignant germ cell tumor because of an anterior mass shadow, gynecomastia, atrophic testis and a high level of HCG. Chromosomal analysis showed a total of 47 XXY. Median sternotomy revealed a tumor originating from the right lobe of thymus. The postoperative course and 2 year follow-up have been uneventful. PMID- 4032870 TI - [Effects of sex hormones on breathing during waking and sleep]. PMID- 4032871 TI - [Abnormal breathing during sleep in patients with chronic respiratory failure]. PMID- 4032872 TI - [Nocturnal desaturation in patients with chronic lung disease--with special reference to the effect on pulmonary circulation]. PMID- 4032873 TI - [Effects of oxygen administration in sleep-induced apneas]. PMID- 4032874 TI - [Immunotherapy by polyvalent bacterial antigen (broncasma berna) for chronic lower respiratory infectious disease]. PMID- 4032875 TI - [A histopathological study on vascular and interstitial changes in the lungs of collagen diseases and a comparison with interstitial pneumonia]. PMID- 4032876 TI - [Long-term oxygen therapy of primary pulmonary hypertension]. PMID- 4032877 TI - [Descent gradient of maximal expiratory flow-volume curve and uneven distribution of ventilation]. PMID- 4032878 TI - [Early clinical symptoms and signs of paragonimiasis westermani, time course when intradermal test with Paragonimus westermani antigen turns positive and effects of praziquantel on paragonimiasis]. PMID- 4032879 TI - [Anaphylactoid reaction to hydrocortisone succinate in three aspirin-sensitive asthmatic patients]. PMID- 4032880 TI - [A case of chronic necrotizing pulmonary aspergillosis]. PMID- 4032881 TI - [Alveolar microlithiasis--a case report]. PMID- 4032882 TI - [Twelve cases of congenital coronary artery fistulas--an experience of "the postoperative development of a new fistula"]. PMID- 4032883 TI - [Evaluation of acute intravascular hemolysis after prosthetic cardiac valve replacement]. PMID- 4032884 TI - [A new trial of a surgical procedure for funnel chest]. PMID- 4032885 TI - [Ascites trocars for Brock's operation]. PMID- 4032886 TI - [Usefulness of angled scalpels in mitral commissurotomy]. PMID- 4032887 TI - [Clinical study of the William Harvey H-1700 oxygenator for open heart surgery]. PMID- 4032888 TI - [Particularity of infundibular stenosis with VSD and right aortic arch--clinical experiences]. PMID- 4032889 TI - [A surgical case of a giant right coronary artery to a left ventricular fistula]. PMID- 4032890 TI - [A surgical case of simultaneous bilateral double primary lung cancers]. PMID- 4032891 TI - [Left atrial myxoma--report of a case having cardiac preoperative symptoms for twenty-six years]. PMID- 4032892 TI - [A case of congenital kinking of the aortic arch]. PMID- 4032893 TI - [Isolated discrete infundibular stenosis]. PMID- 4032894 TI - [A case of typical bronchial carcinoid secreting bradykinin]. PMID- 4032895 TI - [A case of pulmonary chondrohamartoma observed as a slight density on 67Ga scintigraphy]. PMID- 4032896 TI - [Dietary management of renal stone disease--with special reference to oxalate]. PMID- 4032897 TI - [Percutaneously recorded electrical activity of the fourth sacral nerve from sacral foramen (I). Percutaneous recording of the fourth sacral nerve activity in rabbits]. PMID- 4032898 TI - [Percutaneously recorded electrical activity of the fourth sacral nerve from sacral foramen (II). Percutaneous recording of the fourth sacral nerve activity in patients]. PMID- 4032899 TI - [Urinary oxalate excretion in the patients with upper urinary tract calculi]. PMID- 4032900 TI - [Thermal analysis of passed upper urinary tract stones]. PMID- 4032901 TI - [Paraneoplastic syndrome of renal cell carcinoma]. PMID- 4032903 TI - [Electron microscopic studies on the histogenesis of testicular tumor. 2. Fine structure of intratubular atypical germ cell]. PMID- 4032902 TI - [Intravesical recurrence and malignant progression in superficial bladder tumors]. PMID- 4032904 TI - [Clinicostatistical study of penile carcinoma]. PMID- 4032905 TI - [Carcinoid tumor of the kidney]. PMID- 4032906 TI - [The clinical study of renal cell carcinoma with tumorous caval thrombus]. PMID- 4032907 TI - [Studies of heterotransplantation of transplantable human urogenital malignant neoplasms. Part VI. Radiation therapy of human urinary bladder cancer and human prostatic cancer transplantable to nude mice]. PMID- 4032909 TI - [Studies on bladder cancer by flow cytometry. I. Evaluation of the malignant potential of bladder cancer based on flow cytometric DNA analysis]. PMID- 4032908 TI - [Studies of heterotransplantation of transplantable human urogenital malignant neoplasms. Part VII. Combined chemo-radiation therapy of human urinary bladder cancer and human prostatic cancer transplantable to nude mice]. PMID- 4032910 TI - [Congenital megaureter with a long narrow segment in children]. PMID- 4032911 TI - [The determination of urinary oxalate by gas-chromatography]. PMID- 4032912 TI - [Studies on contact-micro-cystoscopy. I. Observation of the bladder epithelium with the contact-micro-colpohysteroscope]. PMID- 4032913 TI - [Heterogeneity of renal cell carcinoma. II: Studies on tumorigenicity of cultured cell line KU-2]. PMID- 4032914 TI - [Evoked responses of the bulbocavernosus reflex: with special reference to its clinical usefulness and problems]. PMID- 4032915 TI - [Clinical studies on medullary sponge kidney]. PMID- 4032916 TI - [Studies of human lactate dehydrogenase-x (C4) [LDH-X(C4)]. 1. Purification of human LDH-X(C4)]. PMID- 4032917 TI - [Results of radiation therapy of bladder tumors: with special reference to the significance of preoperative irradiation]. PMID- 4032918 TI - [Statistical observations on our bladder tumor registry. I. Survival rates of 1120 patients]. PMID- 4032919 TI - [Experimental study of hydronephrosis. Urinary components and functional recovery of hydronephrosis]. PMID- 4032920 TI - A simple catheterization from the ear vein into the jugular vein for sequential blood sampling from unrestrained pigs. PMID- 4032922 TI - Analysis of tissue creatine phosphokinase isoenzymes by histoelectrophoresis. PMID- 4032921 TI - Relationship between serum total cholesterol levels before calving and occurrence rate of diseases after calving in Holstein heifers and cows. PMID- 4032923 TI - Variations of synlophe of Orientostrongylus ezoensis Tada, 1975 (Nematoda: Heligmonellidae) among different populations in Japan. PMID- 4032924 TI - Histochemical observations of lipid droplets in mouse embryos. PMID- 4032925 TI - Elevation in blood sialic acid and mucoprotein levels during hepatic abscess in cattle. PMID- 4032926 TI - Isolation of salmonellae from apparently healthy fattening male dairy calves and fattening pigs and stability of plasmids in the isolates. PMID- 4032927 TI - Morphogenesis of the subcommissural organ in the hamster. PMID- 4032928 TI - Concentrations of total and ionic calcium, inorganic phosphorus, magnesium, and protein in maternal and fetal blood and in amniotic fluid in parathyroidectomized pregnant rats. PMID- 4032929 TI - Therapeutic effects of vitamin K for hemorrhagic disease in pigs. PMID- 4032930 TI - The bacteriological safety of unpasteurized cured meat products in response to the manufacturing processes. PMID- 4032931 TI - Oligodendroglioma in an aged rat. PMID- 4032933 TI - Does the deep brachial artery exist in domestic animals? PMID- 4032932 TI - Developmental EEG of the beagle dog under xylazine sedation. PMID- 4032934 TI - Functional disorders in the peripheral neuromuscular system induced by gonyautoxins in rabbits. PMID- 4032935 TI - Distribution and incidence of calcified lesions in DBA/2NCrj and BALB/cAnNCrj mice. PMID- 4032936 TI - Isolation of a bacteriophage in Fusobacterium necrophorum. PMID- 4032937 TI - Caseous granulomas in bovine paratuberculosis. PMID- 4032939 TI - Duration of the complement-fixation antibodies induced in pigs and guinea pigs by Haemophilus pleuropneumoniae vaccine. PMID- 4032938 TI - The incidence of Rhodococcus (Corynebacterium) equi in domestic animals and soil. PMID- 4032940 TI - Lymphatic metastasis in a case of feline peritoneal mesothelioma. PMID- 4032941 TI - Pregnancy with IUD in situ. PMID- 4032942 TI - Prognostic factor analysis in adult acute leukemia during the period of 1973 to 1983. PMID- 4032943 TI - Effect of epidural morphine on urinary catecholamine excretion during postoperative period. PMID- 4032945 TI - [Numerical classification of Mycobacterium nonchromogenicum, Mycobacterium terrae and Mycobacterium triviale]. PMID- 4032944 TI - [Studies on tuberculosis patients staying in hospitals or sanatoriums for long periods (Part 1)]. PMID- 4032946 TI - [A case of intractable pulmonary infection due to Mycobacterium fortuitum resulting in respiratory failure]. PMID- 4032947 TI - [Efficacy of mass roentgenography in occupational groups]. PMID- 4032948 TI - [Studies on lung disease due to non-tuberculous mycobacteria in Japan (report of the year 1983 of the Mycobacteriosis Research Group of the Japanese National Chest Hospitals)]. PMID- 4032949 TI - [Studies on the factors of staying in hospital and sanatorium for long periods in tuberculosis patients (Part 2)]. PMID- 4032950 TI - [A case of pulmonary infection due to Mycobacterium intracellulare developing after pulmonary embolism]. PMID- 4032951 TI - [Our treatment experience with peacetime chest injuries]. PMID- 4032952 TI - [Late results of stratified plastic repair in the surgical treatment of inguinal hernias with reinforcement of the posterior wall of the inguinal canal]. PMID- 4032953 TI - [Neurogenic bladder--Boschammer's myoplasty]. PMID- 4032954 TI - [Case report on the relativity of the contraindications for duodenopancreatic resection]. PMID- 4032955 TI - [Case report of carcinoma of the small intestine]. PMID- 4032956 TI - [Secondary echinococcosis--asymptomatic course of echinococcosis of the left kidney and the 11th and 12th ribs]. PMID- 4032957 TI - [Acute appendicitis in the neonatal period]. PMID- 4032959 TI - [Case of chronic appendicitis in irreducible femoral hernia]. PMID- 4032960 TI - [Case report of synchronous multiple primary malignant tumors of the digestive tract]. PMID- 4032958 TI - [2 cases of nephrolithiasis and intraoperatively established malignant kidney tumor]. PMID- 4032961 TI - [2 cases of unavoidable abdominal operations in patients with severe heart damage]. PMID- 4032962 TI - [Wirsung's duct-jejunal anastomosis with simultaneous papilloplasty based on endoscopic retrograde cholangiopancreatography]. PMID- 4032963 TI - [Case of incarcerated spigelian hernia]. PMID- 4032964 TI - [Case of a favorable outcome in total biliary peritonitis of unknown origin]. PMID- 4032965 TI - [2 cases of an abscess formation in retroperitoneal hematoma]. PMID- 4032966 TI - [Modern development of anesthesia, resuscitation and intensive therapy in Bulgaria]. PMID- 4032967 TI - [Bilateral retinal detachment in children and adolescents]. PMID- 4032969 TI - [Complications observed after cerclage of the eyeball in the surgical treatment of retinal detachment]. PMID- 4032968 TI - [Problems of operations for retinal detachment after the age of 65]. PMID- 4032970 TI - [Intraocular hypertension as an intraoperative complication in retinal detachment]. PMID- 4032971 TI - [The fate of the eye after an operation for retinal detachment with non-reapposed retina]. PMID- 4032973 TI - [Complications after treatment of retinoblastoma with radioactive cobalt and xenon photocoagulation]. PMID- 4032972 TI - [Complications of surgical treatment of retinal detachment in forensic expert testimony]. PMID- 4032974 TI - [Surgical treatment of idiopathic retinal detachment by temporary balloon scleral buckling]. PMID- 4032975 TI - [Cerclage with a silicone band as the method of choice in the treatment of severe forms of retinal detachment]. PMID- 4032976 TI - [Correlation between the method of xenon photocoagulation and the state of the retina in patients with diabetic retinopathy]. PMID- 4032977 TI - [Vitreous body hemorrhage as a sign of retinal tear]. PMID- 4032978 TI - [The TO-01 ophthalmological thermometer for controlling the temperature of the sclera during diathermocoagulation]. PMID- 4032980 TI - Effect of diuresis on urinary erythrocyte morphology in glomerulonephritis. AB - The differentiation between glomerular and non-glomerular haematuria by phase contrast microscopy has proved to be a useful tool in the diagnosis of glomerulonephritis. In an attempt to evaluate the effect of marked diuresis on the altered red cell morphology in patients with biopsy proven glomerulonephritis, urinary sediments were examined following water or furosemide induced diuresis. In both diuretic states urine flow increased, urine osmolality decreased and the percentage of glomerular erythrocytes was significantly reduced in the urinary sediment. These data demonstrate that the alteration in urinary red cells in glomerulonephritis is mainly caused by tubular forces. The diagnostic significance is reduced during increased diuresis and the evaluation of urinary red cell morphology should not be performed. PMID- 4032979 TI - [Effect of physical training on blood flow properties in patients with intermittent claudication]. AB - Abnormal blood flow in patients with intermittent claudication can be normalized by physical training. We found a decrease in blood viscosity with a decrease in the erythrocyte-aggregation tendency and significant simultaneous improvement in erythrocyte filtrability. Improvement in these haemorheological properties led to a significant increase in physical performance after training. This positive result can be obtained by regular physical training; the application of rheologically effective medicaments is not necessary. PMID- 4032981 TI - The fatty acid composition of red cells deficient in glucose-6-phosphate dehydrogenase and their susceptibility to lipid peroxidation. AB - Oxidant damage to red cell membranes could play a part in the pathogenesis of acute and chronic haemolysis in glucose-6-phosphate dehydrogenase deficiency. Therefore, we studied the substrate for red cell membrane lipid peroxidation, i.e. the content of various polyunsaturated fatty acids in ghosts, and the susceptibility of red cells to lipid peroxidation in normal subjects and in subjects deficient in glucose-6-phosphate dehydrogenase. The fatty acid composition of red cell membranes and plasma was analysed by capillary column gas chromatography. The sensitivity of red cells to lipid peroxidation was evaluated after hydrogen-peroxide-induced oxidant stress. The degree of lipid peroxidation was monitored by measuring the release of pentane and ethane formed during the breakdown of n-6 and n-3 fatty acids. The red cell sensitivity to lipid peroxidation was found to be higher in subjects with glucose-6-phosphate dehydrogenase deficiency than in normal subjects. In the former, saturated fatty acids, in particular palmitic and stearic acid, were found to be decreased, whereas the proportion of arachidonic acid showed a clear increase. Fatty acid analysis of plasma did not reveal significant abnormalities in enzyme-deficient patients, which could explain the alteration of membrane fatty acids. Our results suggest that the increased content of substrate for lipid peroxidation, particularly arachidonic acid, in red cell membranes of subjects deficient in glucose-6-phosphate dehydrogenase, should be considered in an evaluation of an enhanced sensitivity to red cell lipid peroxidation. PMID- 4032982 TI - [Histiocytosis X. Follow-up for over 20 years in a patient with Hand-Schuller Christian disease]. AB - Since 1963 we have observed a patient with Hand-Schuller-Christian disease with involvement of the skeleton, skin and hypophysis/hypothalamus with diabetes insipidus. The diabetes insipidus was successfully treated initially with chlorpropamid and later with carbamazepin. Alterations of the lung parenchyma were seen radiologically in 1966, and two years later the patient complained of exertional dyspnea. The lung disease was progressive with the deterioration of lung function despite corticosteroid and D-penicillamine treatment. The patient now has marked dyspnea even at rest. The osteolytic lesions have not changed in recent years. PMID- 4032984 TI - Haemoglobin D-beta-thalassaemia in a German family. A double heterozygous haemoglobinopathy. AB - This report concerns a young woman, whose stained blood films revealed a hypochromic and microcytic red cell morphology. It could be shown by haemoglobin analysis that this atypical blood film was due to a double heterozygote disorder of haemoglobin D (Hb D) and beta-thalassaemia. The thalassaemia trait was inherited from her father and the Hb D from her mother. This is the first observation of this rare disorder in a German family. Comparable cases reported in the literature are mentioned. PMID- 4032983 TI - Aspects of splenic hypofunction in old age. AB - The weight of the human spleen decreases in old age. The percentage of erythrocytes with pits observed by interference contrast microscopy was significantly higher in 39 elderly subjects (median 4.2%, range 1.2%-14.6%) than in 34 younger controls (median 1.4%, range 0.6%-6.2%). Further evidence of splenic hypofunction was obtained from 7 elderly people with increased pit counts: the removal from circulation and accumulation into the spleen of heat damaged autologous erythrocytes was abnormally slow. However, no difference in the spleen area of the same subjects measured by scintillation scanning was observed in comparison with normals. Thus, the weight reduction of spleen in old age is accompanied by a decrease in splenic function. PMID- 4032985 TI - [Epidemiology of AIDS]. PMID- 4032987 TI - [DNA content of lymphocytes and mononuclear tumor cells in Hodgkin's disease]. AB - Thirteen lymph node biopsy specimens with Hodgkin's disease (six cases of the nodular sclerosis type; six cases of the mixed cellularity type; one case of the lymphocytic depletion type) were studied with scanning cytophotometric measurements. The DNA content of small lymphocytes, large lymphocytes, atypical mononuclear cells and Hodgkin cells was measured. The sizes of the nuclei and mitotic indices were also measured. There were no lymphocytes with aneuploid DNA stemlines. Large lymphocytes showed proliferative activity which is possibly reactive, although its neoplastic character cannot be excluded. Hodgkin cells exhibited aneuploid values in seven cases and atypical mononuclear cells in only four cases. The nuclear sizes and the DNA content of the atypical mononuclear cells ranged between the values of lymphocytes and Hodgkin cells. The mixed cellularity type showed higher DNA values, more frequently occurrence of aneuploid stemlines and a higher frequency of mitotic figures than did the nodular sclerosis type. The results confirm the different grades of malignancy of the various histopathological categories of Hodgkin's disease. PMID- 4032989 TI - Acute bilateral brachial plexus neuritis associated with hypersensitivity vasculitis. A case report and review of literature. AB - The occurrence of brachial plexus neuritis during the acute phase of vasculitis is uncommon. We describe a patient with a long history of rhinitis and a recent onset of asthma, who developed purpuric skin lesions, abdominal pain, eosinophilia and brachial neuritis along with evidence of sacral plexus neuropathy. High dose steroids and cyclophosphamide induced a remission. He stopped all medications after 3 years and after 6 years the patient has some fixed minimal residual neurological deficit. The importance of aggressive therapy in treating extensive polyneuropathy during the acute phase of hypersensitivity vasculitis is raised. A possible cytotoxic role of eosinophils in the pathological process is suggested. PMID- 4032988 TI - [Pharmacokinetic and cardiac efficacy of beta-acetyldigoxin and digitoxin in combination therapy with diltiazem]. AB - The effect of diltiazem (D) on the pharmacokinetics and pharmacodynamics of beta acetyldigoxin (AD; n = 12) and digitoxin (DGT; n = 10) was studied in 22 patients with cardiac insufficiency stages II-III by the New York Heart Association. Glycoside plasma concentration and renal excretion as well as electrocardiogram [heart rate, atrioventricular transconduction time (PQ), duration of electrical systole corrected for heart rate (QTc), mean amplitude of T-waves in leads V2 to V6 (TV2-6)] and systole time intervals [total electromechanical systole index (QS21), left ventricular ejection time index (LVETI), pre-ejection period index (PEPI), PEP/LVET ratio] were recorded repeatedly before and during co administration of 180 mg/day D. In eight patients digoxin plasma levels increased continuously during additional D administration. After reaching a new steady state at 0.93 +/- 0.35 ng/ml digoxin concentrations were at an average 43% higher than before D administration (0.65 +/- 0.27 ng/ml) with a simultaneous increase in renal glycoside excretion. The other four patients showed neither changes in digoxin concentrations in plasma nor in renal glycoside excretion. Only half the patients treated with DGT and D revealed an increase in DGT plasma levels of 21.4%. Daily renal glycoside excretion was not altered by D administration. In accordance to the increasing AD plasma concentration, PQ-interval was prolonged and T-wave flattening was intensified, whereas the systolic time intervals after concomitant treatment of AD and D did not differ from those after AD alone.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4032990 TI - [Renin-angiotensin-aldosterone system and water-electrolyte metabolism in salmonellosis]. PMID- 4032986 TI - Comparison of 131I-metaiodobenzylguanidine scintigraphy with urinary and plasma catecholamine determinations in the diagnosis of pheochromocytoma. AB - In a retrospective study of 31 patients with suspected pheochromocytoma we examined the preoperative results of 131I-metaiodobenzylguanidine (131-I-MIBG) scintigraphy and a fluorimetric urine catecholamine determination test. An additional radioenzymatic plasma catecholamine determination test was performed in 25 patients. In 14 of the 31 patients the diagnosis of pheochromocytoma was later histologically confirmed. In the remaining 17 patients the suspected diagnosis was finally rejected after a clinical decision had been made on the basis of clinical history, symptoms, laboratory and imaging tests. 131-I-MIBG scintigraphy apparently had a very high specificity (no false-positive results among the patients with rejected diagnosis), but showed the least sensitivity (3 of 14 tumours were not detected). Urine catecholamines showed two false-negative and three false-positive results. Plasma catecholamines had the highest sensitivity and gave only one false-positive result. Because of its high pathognomonic value 131-MIBG scintigraphy can be helpful not only for localization, but also for confirmation of diagnosis when catecholamine determination tests are contradictory. On the basis of our experience with false positive results after interfering medication therapy, urine and plasma catecholamine determination tests should only be carried out after purification with thin layer chromatography or high performance liquid chromatography. PMID- 4032991 TI - [Food toxinfections in chronic alcoholics]. PMID- 4032992 TI - [Hemosorption in the combined treatment of leptospirosis patients in the liver kidney failure stage]. PMID- 4032993 TI - [Spontaneous panniculitis (the Rothmann and Makai form)]. PMID- 4032994 TI - [Unusual neurological complication in chronic nonspecific ulcerative colitis]. PMID- 4032995 TI - [Case of malignant neurofibroma of the cervicobrachial plexus]. PMID- 4032996 TI - [Control of student knowledge in a clinical discipline]. PMID- 4032997 TI - [Hemodynamic variants of the crises in hypertension and the adequacy of the pharmacotherapy]. PMID- 4032998 TI - [N-acetyltransferase activity in persons with sclerotic vascular lesions]. PMID- 4033000 TI - [Clinical aspects of internal diseases in a period of the differentiation of clinical disciplines]. PMID- 4032999 TI - [Electrolyte balance characteristics of the myocardium in patients with paroxysmal supraventricular disorders of the the cardiac rhythm]. PMID- 4033001 TI - [Pathogenesis of ischemic disorders of the cerebral circulation in arterial hypertension]. PMID- 4033002 TI - [Analysis of the fatal outcomes during an attack of bronchial asthma]. PMID- 4033003 TI - [Formes frustes of bronchial asthma]. PMID- 4033004 TI - [Cellular and humoral immunity indices of bronchial asthma patients as affected by vaccinotherapy]. PMID- 4033005 TI - [Electromyographic control of hypnotherapy in bronchial asthma]. PMID- 4033006 TI - [Mechanisms of the development of the clinical picture of chronic obstructive bronchitis]. PMID- 4033007 TI - [Fibrosing variant of Wegener's granulomatosis simulating bronchogenic cancer]. PMID- 4033008 TI - [Differential diagnostic importance of determining lactate dehydrogenase in stomach biopsies]. PMID- 4033009 TI - [Clinical x-ray characteristics of primary isolated stomach lymphomas]. PMID- 4033010 TI - [Stomach function and morphology in eczema and neurodermatitis patients]. PMID- 4033011 TI - [Characteristics of the course of the glomerulonephritic form of gouty nephropathy]. PMID- 4033012 TI - [Chronic intravascular coagulation in diabetic microangiopathy patients]. PMID- 4033014 TI - [State of mucous membrane of the upper segments gastrointestinal tract in patients with chronic kidney diseases]. PMID- 4033015 TI - [Functional state of the kidneys after surgical treatment of acute cholecystitis]. PMID- 4033013 TI - [Clinical aspects and treatment of acute HBsAg-positive hepatitis]. PMID- 4033016 TI - [Tolerance to physical exertion and the state of microcirculation in patients with iron-deficiency anemia]. PMID- 4033018 TI - [Clinical course of familial hyperuricemic lesions of the kidneys]. PMID- 4033019 TI - [A case of congenital analbuminemia]. PMID- 4033017 TI - [Clinical forms of a protracted course of anaphylactic shock caused by pyrazole preparations]. PMID- 4033020 TI - [Use of hemosorption in the complex treatment of patients with Lyell's syndrome]. PMID- 4033021 TI - [Acute intermittent porphyria]. PMID- 4033022 TI - [Medullary cystic disease of the kidneys in an adult]. PMID- 4033023 TI - [Primary chronic tuberculosis with Poncet's rheumatoid syndrome resulting in Landouzy's typhobacillosis]. PMID- 4033024 TI - [General principles of management of patients with kidney diseases]. PMID- 4033025 TI - [Classification of chronic bronchitis]. PMID- 4033026 TI - [The problem of dermatomyositis in patients with primary multiple malignant tumors]. PMID- 4033027 TI - [Risk factors in the development of steroid-induced hypertension in patients with nephritis]. PMID- 4033028 TI - [Hypereosinophilic bronchial asthma]. PMID- 4033029 TI - [Drug-induced nephritis]. PMID- 4033030 TI - [Lesions of the spleen in sarcoidosis]. PMID- 4033031 TI - [Hormones regulating phosphorus-calcium metabolism in patients with systemic lupus erythematosus nephritis and Bright disease]. PMID- 4033032 TI - [Plasma thyrotropic hormone level in arterial hypertension of different origins]. PMID- 4033033 TI - [Role of the complement system in the pathogenesis and differential diagnosis of different variants of bronchial asthma]. PMID- 4033034 TI - [Serum parathyroid hormone and calcitonin levels in bronchial asthma in relation to glucocorticoid therapy]. PMID- 4033035 TI - [Objectives of the All-Union and Republics' scientific medical societies in the propagation of the achievements of medical science and their introduction to public health practice]. PMID- 4033036 TI - [Possible mechanisms of the asthmogenic effect of egg white in patients with bronchial asthma]. PMID- 4033037 TI - [Effect of long-term glucocorticoid therapy on thyroid function in patients with bronchial asthma]. PMID- 4033038 TI - [Proteinuria--a symptom or one of the pathogenetic factors of glomerulonephritis?]. PMID- 4033039 TI - [Clinical interpretation of morphological changes in the kidneys in patients with hypertension in its initial stages]. PMID- 4033040 TI - [Water-electrolyte balance and functional state of the kidneys in cosmonauts after a 185-day space flight]. AB - Fluid-electrolyte metabolism and renal function of the crewmembers of the 185-day space flight were examined. Various changes in fluid-electrolyte metabolism and its regulation were seen in the Commander and Flight-Engineer. As most other crewmembers who performed similar flights, Cr showed fluid and sodium retention, whereas FE displayed higher than preflight sodium excretion in the urine. These differences were associated with individual variations of regional hemodynamics which modified the renin-angiotensin-aldosterone system in a different manner. Postflight both crewmembers showed a higher excretion of bivalent ions. The higher excretion of calcium was accompanied by a lower concentration of total and ionized calcium in the serum as well as by a lower concentration of PTH and calcitonin. The loading KC1 test made it possible to assess variations in potassium metabolism that occurred during flight. They included the inability of tissues to retain potassium due to atrophic processes which developed in the weightless state and due to the unloading of the musculoskeletal system. PMID- 4033041 TI - [Resistance to +Gz and +Gx loads of subjects in older age groups, healthy and with initial signs of atherosclerosis]. AB - Tolerance to +Gz and +Gx acceleration of healthy and atherosclerotic subjects, aged 40-49, was investigated during 256 centrifugation tests in Bulgaria and the USSR. As compared to the healthy people, the atherosclerotic subjects showed a lower tolerance: when exposed to 7 +Gz the tolerance threshold decreased from 5.93 +/- 0.57 g to 5.7 +/- 0.44 g (i. e. by 0.23 g). Visual disorders in the healthy and atherosclerotic subjects were recorded in 29 and 50%, respectively, and loss of consciousness in 9.56 and 15.15%, respectively (Bulgarian data). When exposed to 5 +Gz and 6 +Gx no subjects displayed visual disorders or loss of consciousness (Soviet data). However, lower tolerance of 5 +Gz due to cardiac arrhythmias was observed in 4.8% atherosclerotic patients and in none healthy subjects. Lower tolerance to 6 +Gx associated with cardiac arrhythmias was recorder in 23.8% atherosclerotic versus 11.8% healthy subjects (i. e. 12% more). Nevertheless, in most subjects, both healthy and atherosclerotic, acceleration tolerance was good. These findings indicate that individual assessment of acceleration tolerance is of great importance for people older than 40 years with health abnormalities. PMID- 4033042 TI - [Effect of hypokinesia and +Gz loads on the transport function of blood in man]. AB - The results of 44 studies of circulation parameters and blood transport function of 14 test subjects exposed to 7-day bed rest (-10 degrees head-down tilt) and acceleration -4.5 Gz have demonstrated that the blood transport carriers and their actively binding centers form working structures in the adaptive reactions. As compared to the pretest level, the distribution ratio of 14C-adenine between two immiscible phases (plasma/oil, erythrocytes/oil) varies from -12 to 14% on bed rest day 3 to +32 to 40% on bed rest day 7; it increases by 145-150% after exposure to acceleration +4.5 Gz. The parameters of the blood transport function give a quantitative description of its adaptive reactions to environmental effects. PMID- 4033043 TI - [Oxygen status and regional blood flow in the gingival mucosa as affected by lower body negative pressure]. AB - Five test subjects were exposed to lower body negative pressure (LBNP). During exposure their regional circulation and oxygen balance of the gingival mucosa were measured and electrocardiography and kinetocardiography were performed to calculate parameters of the left heart function. The study showed a distinct correlation between LBNP tolerance and the level of compensatory reactions of the gingival mucosa blood flow and the cardiovascular system as a whole. The subjects with a high LBNP tolerance showed well pronounced regional compensatory reactions of the gingival mucosa that were not accompanied by significant changes in the left heart function. The subjects with a moderate tolerance exhibited either weak or no regional compensatory reactions of the gingival mucosa and significant changes in the left heart function. PMID- 4033044 TI - [Effect of water immersion on indices of central hemodynamics in subjects older than 45 years]. AB - The effect of 7-day dry immersion on central hemodynamics of four test subjects, aged 46, with boundary arterial hypertension was investigated. The controls were two healthy men, aged 24. Central hemodynamics was examined by integrated rheography. Variations in blood pressure, central venous pressure, stroke and cardiac indexes, heart rate and total peripheral resistance were measured. The control subjects showed a decrease of blood pressure during exposure (P less than 0.01). Two of the test subjects with a short history of boundary arterial hypertension displayed similar variations (P less than 0.01), whereas two others showed an increase of blood pressure during the immersion period (P less than 0.01). The test and control subjects did not exhibit significant differences in the stroke and cardiac indexes, heart rate, central venous pressure or total peripheral resistance: stroke and cardiac indexes decreased while central venous pressure and total peripheral resistance increased, and heart rate remained unchanged. PMID- 4033045 TI - [Lipid hydrolysis during antiorthostatic hypokinesia in man]. AB - Using present-day techniques, we measured the activity of pancreatic lipase in the serum and duodenal juice, the activity of monoglyceride lipase in the duodenal juice, the concentration of lipoproteins in the bile, the activity of intestinal enzymes (monoglyceride lipase and alkaline phosphatase) and the concentration of lipid fractions in the feces. These parameters were determined in six test subjects who were exposed to head-down tilt (-4.5 degrees) for 120 days. Our findings suggest that bed rest decreases lipolytic enzymes in the duodenal juice and increases pancreatic lipase in the serum. The exposure also leads to a decrease of the lipoproteins in the bile, rearrangement of the lipolytic enzymes in the intestine, and to an increase of mono-, di- and triglycerides in the feces. Our results are indicative of changes in the pancreatic function and in lipid hydrolysis and absorption. They can be interpreted as compensatory-adaptive processes of the digestive organs. PMID- 4033046 TI - [Parity principle and kinematic asymmetries in the otolith system]. AB - Using a mathematical model, otolith stimulation in response to man's movements in a system rotating with a constant angular velocity was examined. Man moved his head or body forward or sideward obeying the trapezoidal rule. The resulting accelerations that acted upon the left and right otoliths were determined. The existence of two otoliths that are symmetrical relative to the sagittal plane was found to be responsible for the left-right asymmetry that accompanied movements in the rotating system, the asymmetry being most distinct during tilts to the left or to the right. PMID- 4033047 TI - [Skeletal musculature of rats during modeling of the physiological effects of weightlessness (morphological study)]. AB - In the experiment rats were suspended in the head-down position (at -15 to -20 degrees) for 21 days. To study the effect of this exposure on skeletal muscles of their fore- and hindlimbs, morphological and histochemical methods were used. Changes in the hindlimbs were similar to those seen in real weightlessness of similar duration. The two antigravitational muscles - soleus and gastrocnemius muscles - showed greatest changes, i.e. atrophic and metabolic shifts. The biceps brachii muscle that changes insignificantly in the weightless state developed a destructive process (with degradation of myofibers) that was later replaced with a reparative process. The changes in this muscle are assumed to be associated with hemodynamic disorders. It is recognized that the method of rat suspension is adequate for a ground-based study of morphological effects of weightlessness on hindlimbs and is unacceptable for that of forelimbs where the exposure induces microcirculation disorders. PMID- 4033048 TI - [Effect of acute hypoxia on coronary and systemic hemodynamics]. AB - Variations in coronary circulation, cardiac output and heart rate were examined by dopplerography in 14 test subjects kept in an altitude chamber. It was found that during acute hypoxia the effective coronary blood flow decreased distinctly prior to general circulatory disorders. It is recommended to monitor coronary circulation during altitude exposures. PMID- 4033049 TI - [Effect of heavy charged particles in galactic cosmic radiation on seeds]. AB - The experiments were carried out on Lactuca sativa seeds exposed for 20, 66, 123 and 308 days in a biostack also containing physical detectors of heavy charged particles. The purpose of the experiments was to measure the yield of aberrant cells and its dependence on the exposure time and the site where particles hit the object. The cytogenetic examination demonstrated a significant difference between the seeds that were or were not hit by heavy charged particles. This is indicative of a significant contribution of galactic cosmic radiation to the radiobiological effect. The yield of aberrant cells as a function of the localization of heavy charged particles in the seed was established. The most sensitive target was the root meristem. PMID- 4033050 TI - [Monitoring volatile substances during conduct of studies in conditions of lowered barometric pressure]. PMID- 4033051 TI - [Determination of individual resistance to the action of hyperbaric oxygen]. PMID- 4033052 TI - [Development of an interactive data processing system for human engineering studies]. PMID- 4033053 TI - [Results of echocardiographic studies of Macaca mulatta monkeys at rest]. PMID- 4033054 TI - [Lipogenesis in the liver of rats following flight on Cosmos-1129 biosatellite]. PMID- 4033055 TI - [Means of resolving frustrating situations by flight and trainee personnel]. PMID- 4033056 TI - Glucose phosphate dehydrogenase polymorphism and the genetics of linkage group II in the Norway rat (Rattus norvegicus). AB - A new variant of glucose phosphate dehydrogenase was discovered in rat erythrocytes and shows autosomal dominant inheritance. The locus, provisionally denoted Gpd, is closely linked to catalase (Cs-1), and there is some evidence that these loci may be assignable to linkage group II. Also in linkage group II, Pgd (6-phosphogluconate dehydrogenase) was found to be linked to b (brown). The linkage between Pgd and b permits linkage group II to be assigned to chromosome 5. PMID- 4033057 TI - Intermittent sampling of portal venous blood and bile from guinea pigs. AB - A technique is described for intermittent collection of portal venous blood from guinea pigs through a catheter advanced from an ileal tributary of the cranio mesenteric vein into the portal vein and for the collection of bile from a catheter in the gallbladder after ligature obstruction of the common bile duct. PMID- 4033058 TI - Urethral plugs and urine retention in male mice. AB - Because MM male mice suffer from a high incidence of urinary tract infection, an assessment was made as to whether the urethral plugs, which occur in male rodents, might be involved in its aetiology. When killed, males more commonly retained urine in their bladders than females but there was no significant difference between strains or method of killing. Males also voided urine more often during stressful handling followed by abdominal pressure, but also retained some urine more often than females. The study of sexually immature mice demonstrated no sex differences and no urine was retained in any bladder. It was concluded that the high frequency of urine retention in mature males is attributable to the presence of urethral plugs but these could not be implicated in the cause of MM urinary tract infection because of comparable findings in the controls. However, the possibility was considered that the plugs might facilitate infection of the kidneys once a bladder infection had become established. PMID- 4033059 TI - A catheter system for long-term intravenous infusion in unrestrained rats. AB - An intravenous catheter system for long-term (at least 6-8 weeks) parenteral nutrition of unrestrained rats is described. The apparatus is inexpensive and can be constructed from commonly available materials. PMID- 4033060 TI - Haematology and pathology of captive southern grasshopper mice (Onychomys torridus). AB - A colony of Onychomys torridus was evaluated for the prevalence of infectious, parasitic and congenital diseases. Multiple limb defects including brachydactyly, syndactyly, and hemimelia were observed in offspring from the colony. The colony was parasitized by Ornithonyssus bacoti (tropical rat mites) on 2 occasions. No infectious diseases were detected. Normal haematologic values were determined in healthy adult animals. PMID- 4033061 TI - A new diabetic strain of rat (WBN/Kob). AB - A new, spontaneously occurring diabetic syndrome has been observed in the aged males of an inbred strain of Wistar rats, WBN/Kob. The main clinical sign, glycosuria, was first detected at about 60 weeks of age, and thereafter some animals developed hyperlipidaemia and gradual emaciation. Prior to the onset of glucosuria, male rats showed impaired glucose tolerance after a glucose load at 21 weeks of age. The histopathologic lesions of the pancreas in the diabetic males consisted of multifocal fibrosis, decreased in number and size of islets and atrophy of exocrine tissue. Multifocal inflammatory foci of varying stages were the main pancreatic lesion in prediabetic male rats. This inflammatory change was detected even in 12-week-old rats and tended to occur around the islets. Therefore focal fibrosis and the decrease in the number and size of islets were considered to result from post-inflammatory scarring. The maturity onset of this syndrome and the impaired glucose tolerance in younger animals suggested that diabetes mellitus of this rat strain is insulin-independent type II. However, the histological lesions of the pancreas were somewhat different from previous reports of both type I and II diabetes mellitus in man and animals. PMID- 4033063 TI - Non-neoplastic lesions of female virgin Han:NMRI mice, incidence and influence of food restriction throughout life span. II: Respiratory tract. AB - A life-span study with 900 female virgin Han:NMRI mice (300 outbred controls, 300 of a fat subline and 300 of a lean subline) was carried out to determine the occurrence of spontaneous diseases with ad libitum or restricted feeding. Rare non-neoplastic lesions of the lungs (1-8%) were secondary inflammations, focal ossification and subintimal arterial 'plaques'. More frequent were age-dependent pulmonary mineralizations similar to psammoma bodies (3-18%) and crystal formations (4-22%). Food restriction did not affect the incidence of these lesions directly. Crystals were observed furthermore within infoldings of the tracheobronchial mucosa and intra- as well as extracellularly in the nasal cavities. PMID- 4033062 TI - Non-neoplastic lesions of female virgin Han:NMRI mice, incidence and influence of food restriction throughout life span. I: Thyroid. AB - A life span study with 900 female virgin Han:NMRI mice (300 outbred controls, 300 of a fat subline and 300 of a lean subline) was carried out to determine the occurrence of spontaneous disease with ad libitum or restricted feeding. The major age-dependent non-neoplastic alteration of the thyroid was a cystic distension of the ultimobranchial bodies (up to 90% in the oldest age groups). Most of the severely cystic thyroids were found in animals of the fat sublines and development seemed to be slightly delayed by food restriction. The cyst walls were composed of ciliated and non-ciliated granular or highly attenuated cells. The cysts contained Alcian blue and periodic acid Schiff positive substances. PMID- 4033064 TI - Monocontamination of germ-free mice by a fastidious unidentified anaerobe. AB - Over a period of several months, 5 germ-free mouse isolators became monocontaminated with seemingly the same fastidious, anaerobic bacilli which defied identification. The organism originated in rodent diet which had been exposed to gamma-irradiation. However, it was discovered retrospectively that the irradiation doses had not been monitored, and subsequent monitoring showed the desired dose of 5 Mrad was not achieved in some parts of the load. Although inadequate sterilization was the likely cause of contamination it was not possible to explain why only this fastidious anaerobe survived the treatment, and not other more common bacterial contaminants. PMID- 4033065 TI - Experiences with standardized feeding of rats with an automatic food dispensing apparatus. AB - A simple automatic food dispensing machine can be used to train rats to a regime of meal-feeding during one hour at night. Apart from some 20% of the animals which fail to adapt but can be recognized early during training on the basis of weight curve, a population of animals is obtained which show a high degree of standardization of rhythmic changes related to food intake and apparently have an adequate supply of food as shown by the protein mass of liver cells. PMID- 4033066 TI - Coordination of the contractile activity of bile canaliculi. Evidence from spontaneous contractions in vitro. AB - Rat hepatocytes, when isolated and maintained in primary culture, are capable of producing forceful contractions of their bile canaliculi, with contractions occurring on a regular basis once every 5.5 minutes. To determine whether the contraction of one bile canaliculus affected the contraction of a neighboring canaliculus, cinephotomicrographic studies of pairs of contiguous canaliculi were undertaken. The activity of 10 pairs of contiguous canaliculi, and 10 pairs of noncontiguous canaliculi which served as a control group, was recorded for a period of 12.5 hours at the rate of 1 frame every 15 seconds. Using frame-by frame analysis of this period of observation, we determined the time of contraction of each of the canaliculi in the pairs. Cross-correlations were obtained for the contraction times of each of the 10 pairs of contiguous canaliculi and 10 control pairs. A peak in activity was found, with that peak occurring five frames or 75 seconds from the midline, whereas the noncontiguous controls showed no correlation in contractile activity. This finding indicates that, when one bile canaliculus contracts, a neighboring canaliculus is likely to contract after an interval of 1.25 minutes. That there is coordination of contractile activity of bile canaliculi suggests that, within the intact liver lobule, ordered motility function of the bile canaliculi may facilitate bile flow. PMID- 4033067 TI - Coordination of the contractile activity of bile canaliculi. Evidence from calcium microinjection of triplet hepatocytes. AB - The discovery that bile canaliculi are capable of spontaneous contractile activity has led to their use in the investigation of the physiology of the liver cell. The contraction of a bile canaliculus is dependent on the network of actin, which is found in the pericanalicular region of the hepatocyte, and agents that inhibit actin filaments interfere with canalicular contraction. Injection of calcium directly into the cytoplasm of one hepatocyte of a cell pair results in contraction. Injection of calcium directly into the cytoplasm of one hepatocyte of a cell pair results in contraction of the canaliculus. To determine whether the contractile activity of adjacent bile canaliculi was coordinated, calcium was injected into one cell of a group of three hepatocytes that formed two neighboring bile canaliculi. Calcium microinjection resulted in contraction of the bile canaliculus contiguous with the microinjected cell and was followed by a contraction of the second, adjacent canaliculus. These secondary contractions occurred after an interval of approximately 45 seconds. The finding that bile canalicular contractions are coordinated with contractions occurring in a sequential fashion supports the hypothesis that, within the liver lobule, transport of bile within the canalicular network results from the coordinated contractions of the canaliculi. PMID- 4033068 TI - Herpes simplex virus type 1 infection of endothelium reduces collagen and fibronectin synthesis. AB - Protein synthesis was assessed in virus-infected and -uninfected cultures of bovine aorta endothelial cells by following the incorporation of [14C]proline into nondialyzable protein and by use of an ELISA assay. Monolayers were infected at confluency by incubating with herpes simplex virus type I at a multiplicity of infection (ratio of virus to cells) of 1.0, 1 hour prior to the introduction of the [14C]proline. Samples were taken from infected and uninfected cultures at various time points postinfection from both medium and cell layer fractions and analyzed for total 14C-labeled protein, 14C-labeled collagen, and 14C-labeled fibronectin. Medium proteins were analyzed by polyacrylamide gel electrophoresis, gel filtration, and electroimmunoblotting. No change was detected in total [14C] incorporation into nondialyzable protein in infected compared with uninfected endothelial cells; however, there was a significant decrease in the synthesis of collagen and fibronectin in infected cultures. The hydroxy[14C]proline content of fractionated medium proteins showed no significant differences between infected and uninfected cultures; therefore, the decrease in collagen synthesis cannot be explained by increased collagen degradation. These data suggest that infection of bovine endothelial cells causes a reduction in the synthesis of collagen and fibronectin. PMID- 4033069 TI - Immunocytochemical identification of estrogen receptor in ovarian carcinomas. Localization with monoclonal estrophilin antibodies compared with biochemical assays. AB - Estrogen receptor (estrophilin) has been identified in ovarian carcinomas by a variety of physicochemical methods. Since these methods require disruption of the tissue, they do not provide any anatomic information about the cellular distribution and location of receptor. The authors have used monoclonal estrophilin antibodies and an indirect immunoperoxidase technique to study the immunocytochemical localization of estrogen receptor in 43 tissue samples of ovarian carcinoma from 27 patients. The immunocytochemical findings were compared with the results of conventional estrogen receptor assays of cytosolic and nuclear extracts prepared from adjacent pieces of ovarian carcinoma. Exclusively nuclear localization of estrogen receptor was observed with the immunocytochemical technique in all of the 25 tumor samples which had a cytosolic estrogen receptor content, determined by either the dextran-coated charcoal or hydroxylapatite techniques, greater than 700 fmoles/gm wet weight of tissue. Only 3 of 16 tumor samples with cytosolic estrophilin concentrations of less than 700 fmoles/gm wet weight displayed nuclear staining for estrogen receptor; two of these three were metastases from receptor-rich primaries. Specific cytoplasmic staining for estrogen receptor was not observed. These results indicate that many ovarian carcinomas have estrogen receptor, predominantly localized in the nucleus, which is similar to tissues of the female genital tract (vagina, cervix, endometrium, fallopian tube) and breast carcinoma. PMID- 4033070 TI - X-ray microanalysis of calcium, potassium, and phosphorus in liver mitochondria stressed by carbon tetrachloride. AB - Previous measurements of elemental concentrations in liver mitochondria have generally required homogenization and fractionation of liver tissue, a procedure in which it is difficult to rule out ion movement between subcellular units. New techniques involving cryoultramicrotomy of rapidly frozen tissue, high resolution scanning transmission electron microscopy, and X-ray microanalysis were used to measure those elements in rat liver mitochondria reported to have changed following oral administration of carbon tetrachloride (CCl4). Increases in liver mitochondrial calcium were found 24 hr following intoxication by CCl4. Significant early (2 hr) mitochondrial increases in potassium and phosphorus were found following administration of CCl4. The electron microscope technique using quick-frozen samples promises to allow measurement of intracellular ionic concentrations under virtually lifelike conditions. PMID- 4033071 TI - Detection and confirmation of urinary cannabinoids. AB - Both a thin layer chromatographic procedure (TOXI-LAB) and two homogeneous immunoassays with differing sensitivity limits (EMIT-st, and EMIT d.a.u.) were used to test 525 urine specimens for metabolites of tetrahydrocannabinol. Negative results were obtained by all techniques for 283 specimens. The EMIT-st was positive for 184 specimens, the EMIT-d.a.u. for 47 additional specimens. The TOXI-LAB results were positive for all these 231 specimens. An additional 11 specimens were positive by EMIT-d.a.u. and negative by TOXI-LAB. Gas chromatography/mass spectrometry analyses of five of these 11 indicated that their average 11-nor-delta 9-tetrahydrocannabinol-9-carboxylic acid concentration was 7.4 +/- 2.2 ng/mL, well below the lower detection limit of the TOXI-LAB procedure. Using both EMIT-d.a.u. and TOXI-LAB assures a reliable urinary cannabinoid analysis above a concentration of 25 ng/mL. PMID- 4033072 TI - Quantitation of cimetidine and cimetidine sulfoxide in serum by solid-phase extraction and solvent-recycled liquid chromatography. AB - A high performance liquid chromatographic method for the simultaneous determination of cimetidine and its major metabolite, cimetidine sulfoxide, was developed. These compounds and the internal standard, ornidazole, were extracted from 0.5 mL of serum using a solid phase Bond Elut C18 analytical column with detection at 229 nm. Absolute recoveries were 94 to 103%, 93 to 104%, and 95 to 105% for cimetidine, cimetidine sulfoxide, and ornidazole, respectively. The minimum detection limit for cimetidine was 0.1 mg/L and for cimetidine sulfoxide was 0.05 mg/L when the concentrating step was used. Cimetidine and cimetidine sulfoxide demonstrated linearity up to 10 mg/L and 7.5 mg/L respectively, with the between-run precision of less than a 5% coefficient of variation for both compounds. Interferences from other drugs tested or endogenous substances in serum were not detected. The mobile phase was recycled to maintain better long term column stability and to minimize solvent cost. The instability of the drugs in solution was circumvented with a reduced-pressure drying process that produced working standards possessing longterm stability. The problem of drug interconversion observed during sample storage and with concentrating steps was controlled also. In addition, a resolution test mixture was chromatographed daily to control chromatographic quality. PMID- 4033073 TI - Determination of triethylenetetramine dihydrochloride in aqueous solution by reversed-phase ion-pairing high performance liquid chromatography and conductivity detection. AB - Triethylenetetramine dihydrochloride (TETA) has been used for the treatment of Wilson's disease which is a metabolic disorder that prevents its victims from eliminating excess copper. TETA was scheduled for toxicological evaluation because of a deficiency of such information. Analytical chemical procedures to determine the purity of the drug as well as the proper concentration and stability of the drug in dosed water were prerequisites for the toxicological tests. A high performance liquid chromatography (HPLC) procedure employing ion pairing and conductivity detection has been developed for the analysis of TETA in dosed water at levels as low as 10 micrograms/mL and for the determination of drug purity. The conductivity detector response was linear over the concentration range of 10 to 100 micrograms/mL. Data are presented concerning the stability of the drug in water during ambient storage and after autoclaving. An ancillary colorimetric procedure for the analysis of aqueous TETA solutions is also presented which is based on measuring the absorbance of the colored TETA copper chelate at 599 nm. The HPLC procedure is applicable to the analysis of TETA and the chemically similar polyamines spermidine and spermine in admixture. PMID- 4033074 TI - Gas chromatographic analysis of metaldehyde in urine and plasma. AB - A gas chromatographic assay specific for the direct analysis of metaldehyde in plasma and urine is reported. This assay takes less than 30 min to perform, has good reproducibility, requires only routine equipment, and has a sensitivity of 1 ng/microL for urine and 2 ng/microL for plasma. PMID- 4033075 TI - Determination of polysorbate in ascites fluid from a premature infant. AB - A method is described for the determination of poly(oxy-1,2-ethanediyl)oligomers in body fluids using ammonium cobaltothiocyanate complexation in conjunction with high pressure liquid chromatography and visible spectrophotometry. Analysis of peritoneal fluid from a baby given E-ferol, a vitamin E supplement, revealed levels as high as 100 micrograms/mL polysorbate. PMID- 4033077 TI - A discussion of principal component analysis. PMID- 4033076 TI - A mescaline associated fatality. AB - The death of an individual under the influence of mescaline is presented. Concentrations of the drug were 9.7, 70.8, and 1163 micrograms/mL or micrograms/g in blood, liver, and urine respectively. PMID- 4033078 TI - A discussion of "unusually high cannabinoid concentrations in urine". PMID- 4033079 TI - Principles of infection, resistance of infection and chemotherapy. PMID- 4033080 TI - Aspects of newborn infection. PMID- 4033081 TI - Urinary tract infections in paediatric practice. PMID- 4033082 TI - Central nervous system infections. PMID- 4033083 TI - Cerebrospinal fluid glucose level, cerebrospinal fluid/blood glucose ratio in the diagnosis of septic meningitis. PMID- 4033084 TI - Aspects of male hypogonadism. PMID- 4033085 TI - An approach to abnormal sexual differentiation. PMID- 4033086 TI - Sex steroid therapy in children and adolescents. PMID- 4033087 TI - An approach to the diagnosis and treatment of Cushing's syndrome in children. PMID- 4033088 TI - The infant of a diabetic mother. PMID- 4033090 TI - Spinal decompression sickness at unusually shallow depth. PMID- 4033089 TI - Hospital mortality in a Singapore paediatric unit. A 20 year review (1964-1983). PMID- 4033091 TI - Absence from work following vasectomy. PMID- 4033092 TI - Cross-sectional study of respiratory effects of arc welding. PMID- 4033093 TI - Review of District Occupational Health Departments for National Health Service staff in the North Western Region of England. PMID- 4033094 TI - An unusual case of mercury contamination. PMID- 4033095 TI - NMR imaging--method and applications. PMID- 4033096 TI - An hypothesis for the role of the spine in human locomotion: a challenge to current thinking. AB - Locomotion was first achieved by the motion of the spine. The limbs came after, as an improvement, not as a substitute; and yet, analysis of bipedal gait concentrates almost exclusively on the motion of the limbs. The requirements for land locomotion are examined from a general point of view and the evolution of the vertebrate spine is presented as a mechanism designed to move the animal. The necessary spinal movements are also analysed; the role of the musculoskeletal system is discussed and it is shown that the lumbar spine is a key structure in land locomotion, the pelvis being driven by the spine. The optimum control of motion demands that the stress at all the intervertebral joints should be minimized and equalized. This theory of locomotion requires the central nervous system to control the torque at those intervertebral joints and suggests that a breakdown of the control system would result in torsional failure of the spine. The theory is supported by EMG, force and torque data collected from several sources. PMID- 4033097 TI - Transient interactions between blood pressure, respiration and heart rate in man. AB - Auto regressive spectral estimation techniques have been used to follow transient interactions between mean blood pressure, respiration and heart rate. This demonstrates that these inter-relationships are variable. It is concluded that while central modulation of heart rate is the major factor in the interactions, when the heart rate is fixed, peripheral modulation of the blood pressure by respiration is clearly demonstrated. PMID- 4033098 TI - Laser Doppler measurements of blood flow in skin tissue. AB - Measurements of blood flow in skin tissue have been made using a low power helium neon laser, with a pair of multi-modal plastic optic fibres to transmit the laser radiation to the skin, one similar fibre to collect the scattered laser radiation, and photodiode detection. Before transmission to the skin surface one of the laser beams is frequency shifted by reflection from a moving corner cube, enabling the experimenter to distinguish between low frequency blood flow dependent signals having a Doppler shift origin, and those low frequency signals generated by other sources of intensity fluctuation such as fibre movement, number fluctuations and laser amplitude modulation. PMID- 4033100 TI - Digital sampling rate and ECG analysis. AB - The influence of sampling rate on the accuracy of measurements of various ECG parameters has been studied. Statistical analysis showed no significant difference between results obtained at sampling rates of 500 and 250 samples s-1. Recordings made at 125 samples s-1, however, showed significant reductions in peak amplitude values. Some interval measurements also varied significantly to both larger and smaller values. Other intervals did not seem to be affected significantly. It is concluded that a sampling rate of 125 samples s-1 could be used in particular conditions when only the measurement of certain intervals is required. PMID- 4033099 TI - Resurfacing elbow prosthesis: shape and sizing of the humeral component. AB - The sizing and dimensioning of a new unconstrained elbow prosthesis makes use of a geometric axis for humeral articulating surface definition, an axis which is precisely positioned with respect to extra-articular anatomical landmarks. The geometry of the joint was determined by a slicing and digitization technique. It was found that for the humerus an axisymmetric surface is evident and that there exists a centroidal axis which is mostly linear except for a portion at the posterior lateral flange of the trochlea. Sizing studies were carried out on dry bone anatomical specimens and, using a standardized X-ray technique, on the elbows of volunteer subjects. Seven dimensions were chosen for statistical analysis of the joint. A multi-variate normal distribution model, using only the first principal component was found to account for 70% of the variance; components 2 and 3 explained a further 19%. From this analysis, one series of three and five sizes of prosthetic dimensions were established for 95% overall coverage of population. PMID- 4033101 TI - Torsional tests of long bones with computerized equipment. AB - An experimental method using a computerized torsion machine to study the mechanics of entire diaphyseal bones is described. Besides controlling continuous torsion to ultimate fracture of the bone, the computer is able to use non linearity of the torque-twist curve as a criterion for reversal of the direction of torsion and to control repeated loadings and unloadings with a graduated increase of deformation until final fracture. It permits determination of a small residual deformation, and several other parameters characterizing the load deformation curve. The linearity of the equipment is shown to be good and precision is high, with a method error of 2.3% when determining stiffness. Repeated loadings and unloadings of entire dog femora revealed a minor residual deformation before ultimate fracture. PMID- 4033102 TI - Tools for high tibial wedge osteotomy. AB - Surgical instruments are described which have been developed for use in high tibial wedge osteotomy. This operation is a treatment for degenerative arthritis of the knee in which one compartment of the joint is predominantly affected resulting in a deformity. Realignment of the bones alters the load distribution on the joint which can relieve pain. Tools have been designed to facilitate the removal of a wedge of bone cut at a precise angle calculated from load bearing radiographs. The tools are a marker pin guide and a saw guide; their use has resulted in accurate bone realignment confirmed by postoperative radiographs. PMID- 4033103 TI - Domiciliary medicine. PMID- 4033104 TI - Compliance, mass, and shape of the canine left ventricle after global ischemia analyzed with two-dimensional echocardiography. AB - End-diastolic pressure (EDP)-volume (EDV) curves were constructed for the left ventricle (LV) in 10 dogs on cardiopulmonary bypass before and after 45 min of normothermic ischemic arrest. LVEDV and mass were calculated from three perpendicular two-dimensional echocardiographic sections using a Simpson's rule algorithm. The echocardiographic method employed was specially developed in earlier work for physiologic studies in dogs. Postmortem pressure-volume curves were measured for comparison by direct saline infusion into sealed ventricles. LVEDV was plotted against LVEDP (0-20 mm Hg) and data were analyzed by two-way analysis of variance and also by exponential curve fitting to the relation EDP = alpha e beta EDV, where beta is the derived exponential constant reflecting slope and thereby ventricular stiffness. Postischemic EDP-EDV curves shifted to the left and the beta constant increased (beta = 0.02 +/- 0.005 (SE) vs 0.05 +/- 0.01, P less than 0.05). LV eccentricity, the ratio between long- and short-axis measurements, was unchanged (1.43 +/- 0.05 vs 1.46 +/- 0.06 postischemia, NS), but LV mass increased (105 +/- 7 vs 128 +/- 9 g postischemia, P less than 0.001). Postischemic LV mass by echo was not significantly different from measured postmortem LV mass (r = 0.87). The nonparallel alteration in the EDP-EDV curves, lack of change in LV shape (eccentricity), and increase in LV mass in the postischemic ventricle suggest that increased ventricular stiffness rather than direct encroachment by the edematous endocardium on chamber volume is responsible for postischemic changes in LV diastolic properties. PMID- 4033105 TI - Enhanced cardioplegic protection by a fluorocarbon-oxygenated reperfusate: a phosphorus-31 nuclear magnetic resonance study. AB - Prolonged global ischemia results in a defect in oxygen extraction during early reperfusion. This study was thus undertaken to assess the effects of maintaining cardioplegia at the onset of reoxygenation in view of channeling available energy toward reparative cell processes rather than mechanical activity. Twenty-four isolated perfused rat hearts were subjected to 120 min of 15 degrees C ischemia. Group I (control) was reperfused with the standard Krebs perfusion medium whereas in groups II and III the initial reperfusate consisted of an oxygenated alkaline cardioplegic solution prior to the resumption of Krebs perfusion. Oxygenation of the cardioplegic reperfusate was ensured by fluorocarbons at a concentration of 10% (O2 content: 5.5 vol %; group II) or 20% (O2 content: 9 vol %; group III). In addition to hemodynamical determinations, high-energy phosphates and intracellular pH were monitored serially by phosphorus-31 nuclear magnetic resonance spectroscopy. After 30 min of reperfusion postischemic recovery of aortic flow was better in group II (74.0 +/- 5.9% of control) than in group I (59.1 +/- 5.4% of control, P less than 0.05). This functional improvement correlated with a higher postischemic increase in phosphocreatine levels (103.21 +/- 11.21% vs 74.12 +/- 3.59%, at 3 min of reperfusion, P less than 0.05) without significant differences in total ATP content. Group III hearts exhibited a slow recovery as evidenced by a severe depression in aortic flow, coronary arteriovenous difference, and total phosphate content during the 15 initial minutes of reperfusion. These results show that the protection provided by cardioplegia can be improved by a fluorocarbon-oxygenated cardioplegic reperfusate.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4033106 TI - Determination of heat gain in the inferior vena cava during thermodilution measurements. AB - The measurement of blood flow in the inferior vena cava (IVC) by thermodilution may be useful in the determination of hepatic venous blood flow (HVBF), but is subject to major errors. The most serious error is gain of heat from the abdominal viscera by the cool thermodiluent bolus as it moves up the IVC. The determination or elimination of this heat gain is necessary for accurate IVC blood flow measurement. By comparison of the area under the curve (AUC) for cardiac output following femoral vein injection of the thermodiluent bolus to the AUC following right ventricular injection of the thermodiluent, it is possible to quantitatively determine the unidirectional heat gain by the bolus at it moves up the IVC. The heat gain varied from 0 to 40% of the thermodiluent injected. The factors that aggravated the heat gain were a low cardiac output (below 4000 ml/mn), a large thermodiluent calorie load (over -40 calories), and possibly a slow transit time. The error due to heat gain may be effectively eliminated by keeping the size of the thermodiluent bolus below 40 negative calories. PMID- 4033107 TI - Comparative hemodynamic effects of selective superior mesenteric arterial and peripheral intravenous glucagon infusions. AB - This experiment was designed to determine whether any hemodynamic benefits attend administration of equal pharmacologic doses of glucagon (1 micrograms/kg/m) by continuous intravenous infusion (Group I, n = 6) versus selective intraarterial infusion (Group II, n = 6) via the superior mesenteric artery (SMA) in dogs. Cardiac output, heart rate, mean arterial pressure, total peripheral resistance, pulmonary vascular resistance, superior mesenteric artery flow (SMAQ), SMA vascular resistance, and portal venous pressure were measured at baseline (BL) and at 5, 15, 30, and 45 min during glucagon infusion. SMAQ virtually doubled at 5 min from a baseline of 570 +/- 60 ml/min to 1158 +/- 146 ml/min in Group I (P less than 0.001), and from a baseline of 527 +/- 171 to 1018 +/- 331 ml/min in Group II (P less than 0.002). SMAQ was significantly higher in Group I at 30 and 45 min compared to Group II (P less than 0.03) despite similar peripheral plasma glucagon levels. SMA vascular resistance was significantly lowered in both groups, with a greater reduction occurring during intravenous glucagon administration at 45 min (P less than 0.05). Changes in systemic hemodynamic parameters, as well as glucagon and glucose levels were not statistically different between Groups I and II at any time period. Glucagon is a potent mesenteric vasodilator and the resultant profound splanchnic hemodynamic effects are as marked during intravenous administration as during selective SMA infusion. PMID- 4033108 TI - Optimal redox electrode potential for 24-hour rabbit kidney perfusion. AB - This study was conducted to determine whether an optimum redox electrode potential existed for 24-hr hypothermic perfusion of rabbit kidneys. The perfusate consisted of a Ringer's-albumin solution to which was added varying amounts of the reducing agents, glutathione and ascorbate, either individually or in equimolar amounts. Electrode potential was monitored with a vitreous carbon electrode in relation to a silver-silver chloride reference cell, and kidney function was measured after preservation by connection to the circulation of a perfusor animal via a shunt. The best results were obtained using equimolar amounts of the reducing agents. Under these circumstances a definite optimum range for perfusate electrode potential was identified (Es = 40-70 mV) within which renal function was indistinguishable from unpreserved controls. Higher and lower perfusate electrode potentials were associated with significantly lower creatinine clearances. However, the explanation for these results appeared to be more complex than redox control alone, since kidney function was dependent not only on the redox potential of the perfusate but also on the reducing agents with which the adjustment had been made. Ascorbate proved to be significantly better than glutathione within the optimum potential range. PMID- 4033109 TI - Evaluation of surgical tapes for wound closure. AB - The performance of four wound closure tapes was evaluated by a series of standardized tests. The tapes examined in this study were a nonwoven microporous tape, a nonwoven microporous reinforced tape, a gauze tape, and a polyurethane tape. The performance of these tapes was assessed by measuring their breaking strength, degree of elongation under loading, adhesion to skin, air and water vapor transmission, and bacterial growth under the tape. On the basis of these in vitro and in vivo studies, the nonwoven microporous tape is recommended for skin closure. This tape has a nonwoven microporous structure with an adhesive that aggressively adheres to the underlying skin. It is strong enough to resist breakage during clinical use and elongates sufficiently to prevent blister formation. Its microporous structure permits rapid air transmission in vitro and results in an environment that is antithetical to bacterial growth. PMID- 4033110 TI - Rupture of the liver in preeclampsia. A review and report of two cases. PMID- 4033111 TI - Management of subclavian vascular injuries. PMID- 4033112 TI - Psychotropic drug use in older people: a review. PMID- 4033113 TI - High risk registry update. PMID- 4033114 TI - Modulation of DNA binding of glucocorticoid receptor by aurintricarboxylic acid. AB - Effects of aurintricarboxylic acid (ATA) were examined on the DNA binding properties of rat liver glucocorticoid-receptor complex. The DNA-cellulose binding capacity of the glucocorticoid-receptor complex was completely abolished by a pretreatment of receptor preparation with 0.1-0.5 mM ATA at 4 degrees C. The half-maximal inhibition (i.d.50) in the DNA binding of [3H]triamcinolone acetonide-receptor complex [( 3H]TARc) was observed at 130- and 40 microM ATA depending upon whether the inhibitor was added prior to or following the receptor activation. The entire DNA-cellulose bound [3H]TARc could be extracted in a concentration-dependent manner by incubation with 2-100 microns ATA. The [3H]TARc remained intact under the above conditions, the receptor in both control and ATA treated preparations sedimented in the same region in salt-containing 5-20% sucrose gradients. The action of ATA appeared to be on the receptor and not on DNA-cellulose. The DNA-binding capacity of ATA-treated receptor preparations could be recovered upon exhaustive dialysis. The treatment with ATA did not appear to change the ionic behavior of heat activated GRc; the receptor in both control and the ATA-treated preparations showed similar elution profiles. Therefore, ATA appears to alter the binding to and dissociation of glucocorticoid receptor complex from DNA. The use of ATA should offer a good chemical probe for analysis of the DNA binding domain(s) of the glucocorticoid receptor. PMID- 4033115 TI - Physical-chemical properties of the estrogen receptor solubilized by micrococcal nuclease. AB - The physical-chemical properties of the nuclear estrogen receptor from MCF-7 cells were determined. The receptor was solubilized by micrococcal nuclease. Nuclei were isolated from cells previously exposed to 10 nM [3H]estradiol. The amount of receptor released was parallel to the extent of chromatin solubilized, which suggested that the receptor is homogeneously distributed on the chromatin. Following mild nuclease digestion the excised receptor sedimented as an abundant 6-7 S form and as a less abundant approximately 12 S species. The 6-7 S form represented the receptor excised in association with linker DNA, while the approximately 12 S may represent receptor bound to linker DNA which remained associated with the nucleosome. Increasing the extensiveness of digestion resulted in one receptor form sedimenting at 5.6 S. Additional digestion with DNase I did not affect the sedimentation coefficient of the receptor. Sedimentation of the micrococcal nuclease hydrolysate in a 0.4 M KCl sucrose gradient resulted in a 4.2 S receptor form. The same receptor form was extracted from undigested nuclei with 0.4 M KCl. Using Sephadex G-200 column chromatography we have determined the Stokes radii (Rs), molecular weight (Mr) and frictional ratio (f/fo) for the 5.6 S and 4.2 S receptor forms. For the 5.6 S form: Rs = 7.04 nm, Mr = 163,000 and (f/fo) = 1.80. For the 4.2 S receptor, Rs = 4.45 nm, Mr = 77,000 and (f/fo) = 1.46. The ability of the nuclease solubilized 5.6 S receptor to bind DNA was tested using DNA-cellulose column and highly polymerized DNA. About 40% of the applied receptor bound to the column and could be eluted by high salt concentrated buffer. The 5.6 S receptor form was sedimented on sucrose gradient by the highly polymerized DNA. These results suggested that the receptor is bound in chromatin as a dimer or as a monomer in association with other protein(s) which complexed it with DNA. PMID- 4033116 TI - Inhibition of fatty acid synthesis in rabbit mammary alveolar explants by progesterone and related steroids. AB - The possible inhibitory effect of steroids related to progesterone on prolactin stimulated fatty acid synthesis in mammary alveolar explants from 11-day pseudopregnant rabbits, after culture, was investigated. Like progesterone, 17 alpha-hydroxyprogesterone, 20 alpha-dihydroprogesterone, medroxyprogesterone acetate, ethinodiol diacetate, ORG 2058 were inhibitory whereas pregnenolone and 5 alpha-pregnan-3,20-dione were not. PMID- 4033117 TI - Circular dichroism study of the interaction between conformationally altered human serum albumin and testosterone. AB - Binding ability of testosterone (TEST) on conformationally altered human serum albumin (HSA) in the presence of several concentrations of NaSCN, urea and KCl at various pH was examined qualitatively on the basis of the rotational strength at 303, 273 and 208 nm by means of circular dichroism (CD). The values of the binding index expressed as a ratio of [theta]303/[theta]273 at each rotational strength in the presence of various concentrations of salt at pH 7.4 were inversely proportional, parallel, and independent of the alpha-helix content based on the peptide backbone alteration of HSA by urea, KCl and NaSCN, respectively. The values in the presence of a constant concentration of 1.0 M urea or KCl at various pH were dependent on the salt, showing a significant effect of these salts on the binding sites of the amino acid chain rather than the peptide backbone of the protein. It was generally observed that the decrease in alpha-helix content caused by pH changes tends to decrease the binding ability of TEST to HSA. The decreased binding index value observed in 40 mM NaSCN causing a low alpha-helix content, suggests that the secondary conformational changes caused by the salt might not be related to the binding ability, in contrast to the results of urea or KCl at different pH. It was clearly demonstrated that the binding ability of TEST to HSA is closely associated with skeletal conformational alterations as well as changes in the binding sites of the amino acid side chains of the protein. PMID- 4033118 TI - The effect of spironolactone on genital skin 5 alpha-reductase activity. AB - The effect of spironolactone (S) on genital skin 5 alpha-reductase activity (5 alpha-RA) of hirsute women (HW) in vivo as well as in normal genital skin in vitro was evaluated. Thirteen HW (Ferriman-Gallwey score of 23.3 +/- 2.8) received S 100 mg twice a day for a month. Twenty-three non-hirsute women were selected as controls for the assessment of genital skin 5 alpha-RA. S was added to incubations of genital skin from 9 additional controls in vitro in concentrations from 1.2 X 10(-8) to 10(-5) M. HW had significantly higher conversion ratios (CR) of T to DHT compared to controls (P less than 0.05). Post treatment values for the CR T to DHT were significantly lower than prior to S (17.5 +/- 1.7 and 8.05 +/- 1.2%, P less than 0.05) and the mass of DHT produced also decreased by 37 +/- 9% (P less than 0.05). The CR T to 3 alpha-diol decreased by 30 +/- 9% (P less than 0.05). In 11 of 13 women, a significant reduction of 5 alpha-RA was demonstrated while in 2 patients the activity remained unchanged. The maximum in vitro inhibitory effect of S on the CR T to DHT occurred with a concentration of 1.2 X 10(-5) M (P less than 0.01). In conclusion, S has a direct inhibitory effect on 5 alpha-RA. The beneficial effect of S treatment in HW may be related, in part, to this inhibition of 5 alpha-RA. PMID- 4033120 TI - Synthesis of 19-hydroxyaldosterone and the 3 beta-hydroxy-5-ene analog of aldosterone, active mineralocorticoids. AB - 19-Hydroxyaldosterone (20) and the 3 beta-hydroxy-5-ene analog of aldosterone (HAA) (8) were synthesized from 21-acetoxy-4-pregnene-3,20-dion-20-ethylene ketal 18, 11 beta-lactone (2) as follows: the double bond was transposed from the 4,5 to the 5,6-position by enol acetylation to 3, followed by sodium borohydride reduction. Further reduction of the resulting lactone 4a with diisobutylaluminum hydride (DIBAH) furnished the 20-ketal of HAA 6, from which free HAA (8) and the 18,21-anhydro compound 7 were obtained by acid treatment. The [1H]NMR spectrum of 8 in CDCl3 showed it to be a mixture of two isomeric forms. Correlation with the known aldosterone-gamma-etiolactone (10) was established by periodate oxidation of HAA to the corresponding etiolactone 9 followed by chromic acid oxidation. The preparation of 20 was next effected in the following manner: the diacetate 4b was converted into the 6 beta, 19-oxido compound 13b by addition of hypobromous acid followed by the hypoiodite reaction of the bromohydrin 11. Mild saponification of 13b lead to the corresponding diol 13a, and was followed by selective oxidation to the 3-one 14, readily dehydrobrominated to 15a. Reductive ring opening furnished a mixture of the 19,21-diol 16a and its 5-ene isomer 16b, which was directly converted to the diketal 17. Reduction with DIBAH gave the hemiacetal 18, and hydrolysis of the latter 19-hydroxyaldosterone (20) as a water-soluble solid, accompanied by the 18,21-anhydro compound 19. 19-Hydroxyaldosterone exists in CHCl3 and water as a mixture of mainly two isomers. Periodate oxidation furnished the etiolactone 21. Preliminary results indicate that HAA and 19 hydroxyaldosterone are active mineralocorticoids in the Kagawa bioassay and short circuit current measurements. PMID- 4033119 TI - Testosterone and dihydrotestosterone levels in epididymis, vas deferens, seminal vesicle and preputial gland of mice after hCG injection. AB - Temporal changes of testosterone (T) and dihydrotestosterone (DHT) levels were measured by RIA in epididymis, vas deferens, seminal vesicle and preputial gland of adult male mice after a single injection of hCG. The response of circulating T to hCG stimulation was rapid and persisted over a period of 48 h. The temporal changes of androgen content of target organs paralleled the modifications of circulating T. In all organs the high androgen levels attained at 1 or 4 h plateaued until 24 h, decreased thereafter and returned to basal values at 72 h. The concentration of T by sex accessory organs was more accelerated by hCG injection than its conversion into DHT. PMID- 4033121 TI - Isolation and identification of 25-hydroxydihydrotachysterol2 1 alpha,25 dihydroxydihydrotachysterol2 and 1 beta,25-dihydroxydihydrotachysterol2. AB - Three metabolites of orally administered dihydrotachysterol2 have been isolated in impure form from serum of rats. These metabolites have been identified as 25 hydroxydihydrotachysterol2 and two epimers of formula 1-ambo,25 dihydroxydihydrotachysterol2 by means of gas chromatography-mass spectrometry and ultraviolet absorption spectrometry. For the first time this provides evidence for 9,10-seco steroid hydroxylation at pseudo C3. The stereochemistry of the 1 hydroxyl group of the two epimers could be established tentatively by quantitative comparison of the mass spectra of their respective trimethylsilyl derivatives. Since purity requirements were not achieved, biological activities could not be determined. PMID- 4033122 TI - Binding of [3H]aldosterone to a single population of cells within the rat epididymis. AB - Using the dry-mount autoradiographic technique, a single population of cells within the rat epididymis, the clear cells, have been shown to bind [3H]aldosterone at a nuclear site. Competitive binding experiments demonstrated that aldosterone was more potent than desoxycorticosterone than testosterone in reducing the nuclear uptake of radioactive aldosterone. Furthermore, the other epididymal cells (principal and basal cells) in all regions of the epididymis were not significantly labelled; occasional labelling was noted in some endothelial and stromal cells. It is suggested that aldosterone may play a role in controlling the intracellular and transcellular movement of ions and water necessary for concentrating absorbed macromolecules in the clear cell. PMID- 4033123 TI - A simple in vitro approach to the estimation of the biopotency of drugs affecting adrenal steroidogenesis. AB - Dispersed guinea-pig adrenal cells can be maximally stimulated to secrete cortisol by adrenocorticotrophin (ACTH greater than 50 ng/l). Further, this stimulation appears to be specific to ACTH alone, with other naturally occurring chemicals (e.g. steroids, protein hormones) at supra-physiological concentrations being without effect on cortisol production. The effect of drugs of differing structure and therapeutic function (aminogluthethimide, metyrapone, trilostane, 17-ketotrilostane, danazol, epostane, megestrol acetate, stanozolol and etomidate) on ACTH-stimulated (50 ng/l) cortisol production has been tested in this system. All the drugs depressed steroid output in a similar dose-related fashion. The concentration of drug which inhibited cortisol output by 50% was (mumol/l, mean +/- SEM): etomidate 0.097 +/- 0.002: epostane 0.44 +/- 0.02: 17 ketotrilostane 0.55 +/- 0.04: trilostane 1.3 +/- 0.1: metyrapone 3.5 +/- 0.6: megestrol acetate, 11 +/- 2: danazol 22 +/- 2: aminogluthethimide 41 +/- 5: stanozolol 50 +/- 4. Thus, etomidate, an anaesthetic, is more potent than the established anti-steroidogenic drugs metyrapone, aminogluthethimide and trilostane. Further, direct anti-steroidogenic effects have been demonstrated for megestrol acetate and stanozolol for the first time. We conclude that this technique offers a promising new approach to the assessment of biological potency of drugs affecting endocrine tissues. PMID- 4033124 TI - The metabolism of estradiol 17-sulfate by pheochromocytoma tissue. AB - The metabolism of estradiol 17-sulfate by subcellular localization enzymes of pheochromocytoma tissue obtained from a 41-year old female was investigated. In any incubations under the presence of NADH and NADPH, metabolites hydroxylated at the C-2, C-4, C-6 beta, C-7 alpha and C-7 beta positions were produced. These hydroxylations are considered to occur without cleavage of the sulfate group. The 2-hydroxylation at the substrate concentration of 100 microM by mitochondria, microsomes and cytosol fractions occurred at rates of 141, 222 and 167 pmol/mg protein/30 min, respectively; the corresponding rates for the 4-hydroxylation were 24, 40 and 38 pmol/mg protein/30 min. Mitochondrial 2- and 4-hydroxylations were enhanced by addition of calcium ion (Ca2+) into the incubation medium. PMID- 4033125 TI - Reactivity to alcohol-related cues: physiological and subjective responses in alcoholics and nonproblem drinkers. AB - Physiological reactivity and self-reported desire to drink in nonproblem drinkers (N = 11 women and 15 men) and hospitalized alcoholics (N = 25 women and 34 men) were examined while subjects held and sniffed their preferred alcoholic beverage. Skin conductance level (SCL) and heart rate during alcohol exposure were significantly higher in the alcoholics than in the non-alcoholics. Self-reported desire to drink and SCL during alcohol exposure were correlated for alcoholics but not for nonalcoholics. Among alcoholics, SCL change was positively correlated with the number of heavy-drinking days in the month preceding admission to treatment. Consistent with conditioning models of relapse, alcoholics showed a distinctive response to alcohol cues, characterized by autonomic reactivity and concordance between this reactivity and self-reported desire for alcohol. PMID- 4033126 TI - A prospective study of young men at high risk for alcoholism: school behavior and achievement. AB - From a large consecutive birth cohort in Denmark, 134 sons of alcoholic fathers (high-risk group) and 70 matched controls were selected for a prospective longitudinal study of alcoholism. A premorbid multidisciplinary assessment was conducted at age 19-20. Data were derived from three sources: a social worker interview, a psychopathological interview that also collected information about current drinking pattern, and a questionnaire sent to teachers. The high-risk group reported having experienced a more disturbed school career, and were rated by their teachers as having been more impulsive and as having had poorer verbal proficiency. These factors may be predictive of future alcoholism. PMID- 4033127 TI - Patterns of alcohol use and physically aggressive behavior in men. AB - Research on the relationship between alcohol use and aggressive behavior has typically focused on arrested felons and has contained minimal data on alcohol use, the symptoms of alcoholism and potential explanatory variables. The present study examined this relationship in a community-based population of blue-collar workers (N = 484 men). Current alcohol consumption was not related to either the number of fights that subjects were involved in since age 18 or physical marital conflict. However, a pathological pattern of consumption and a recent diagnosis (within the previous 3 yr) of alcohol misuse or alcohol dependence were related to physical marital conflict. Furthermore, these relationships remained significant after sociodemographic factors, and hostility and marital satisfaction were controlled for. Thus, these results on aggressive behavior confirm previous findings from research on criminal violence. PMID- 4033128 TI - A cross-ethnic comparison of reasons given for using alcohol, not using alcohol or ceasing to use alcohol. AB - In a study that included six different racial-ethnic groups in Hawaii, the reasons given by drinkers for drinking, abstainers for not drinking and former drinkers for ceasing to drink were assessed. Although there were group differences in frequencies of endorsement of given reasons for drinking, for not drinking or for ceasing to drink, the findings of similarity were most impressive. Drinkers, abstainers and former drinkers were similar across racial ethnic groups in their proportions of endorsement of given reasons for drinking, abstaining or ceasing to use alcohol. Although reasons for drinking varied across racial-ethnic groups, they varied much more across groups that differed in alcohol consumption independent of ethnicity, with all reasons for drinking being more often endorsed as consumption increased. In addition, the citation of more pathological reasons for drinking was associated with a greater number of drinking problems. PMID- 4033129 TI - Effects of family drinking history and expectancies on responses to alcohol in men. AB - The effects of family drinking history and expectancies on responses to alcohol were studied in men nonproblem drinkers aged 19-30. A total of 24 subjects who reported a history of parental alcoholism (FH+) were compared with matched controls who did not have such a family history (FH-) on their responses to drinking either a placebo beverage, a low dose of alcohol or a high dose of alcohol. Despite comparable levels of tolerance and blood alcohol levels (BALs), FH- subjects reported higher levels of intoxication, behavioral impairment, anesthesia and central stimulation than FH+ subjects, regardless of the dose consumed. In contrast, FH+ subjects did more poorly on a timed motor task. There were no significant differences between the two groups on their self-reported beliefs about the effects of alcohol. However, multiple-regression analyses showed that BAL accounted for a greater percentage of the variance in the self report data of FH- subjects, whereas expectancies were more predictive for the FH+ subjects. The results suggest that FH+ subjects did not base their evaluations of the effects of alcohol as closely on the internal and external consequences of intoxication. This finding is discussed as being one component of their heightened risk for developing alcoholism. PMID- 4033130 TI - Employee drinking patterns and accidental injury: a study of four New England states. AB - The relationship between alcohol use and accidental injury was examined in an anonymous telephone survey of 1740 randomly sampled employed adults (49% men) residing in four New England states in 1982 and 1983. Respondents reported 383 accidents requiring medical attention during the year prior to the interview, 34 involving hospitalization. Of the accidents, 41% occurred at work, 32% during recreational and other activities, 19% at home and 8% in traffic incidents. Respondents were stratified by self-reported levels of alcohol consumption and were compared on accident rates. Drinking at work was also examined for an association with accident involvement. Logistic regression analyses controlled for variability associated with age, sex, marital status, occupation and drug use. Drinking at work was not significantly or independently associated with job accidents but an average daily intake of 5+ drinks elevated the relative risk, compared with abstainers, as follows: 1.7 for any accidental injury, 3.8 for injuries requiring hospitalization and 2.0 for job-based accidental injuries. The relative risks associated with the use of other psychoactive drugs were 1.7 for work accidents and 2.4 for accident-associated hospitalizations. Of the respondents, 13% reported having ever had a drug or alcohol problem and 2% reported a current problem. Fourteen percent reported that there were counselors at their jobs to help with such problems. Of those who had ever experienced a problem, 11% had sought help from outside programs and only 4% had sought help at work. PMID- 4033131 TI - Effect of age, sex, drinking history and antisocial personality on neuropsychology of alcoholics. AB - The effects of age, sex, drinking history and the presence of antisocial personality (ASP) on the Wechsler Adult Intelligence Scale (WAIS) and Halstead Reitan Neuropsychological Test Battery subtest scores of alcoholics were examined. Subjects (172 men and 72 women) were recruited from three inpatient alcoholism treatment facilities in the Hartford area and were evaluated approximately 1 week after admission. Brain Age Quotients (BAQ) were computed for each subject. The mean BAQ score for the total sample (84.1) was slightly more than one standard deviation below the normative value. Performance on the WAIS was within normal limits for both verbal and performance IQ. Scores on the Halstead-Reitan Battery showed evidence of moderate levels of impairment. Age was found to be the most significant factor affecting neuropsychological performance. It was observed that alcoholic subjects under 40 years of age performed at the lower end of the normal range of performance; older subjects showed mild to moderately severe levels of impairment. Significant interactional effects were observed between age, amount of alcohol consumed and sex for Tactual Performance Test total time. The presence of ASP interacted with sex to affect performance on Block Design and the Category Test such that ASP men performed at higher levels and ASP women at lower levels than their non-ASP counterparts. The ASP diagnosis also interacted with alcohol consumption to affect scores on Block Design. Possible explanations of these findings are discussed. PMID- 4033132 TI - Effects of alcohol on human aggressive behavior. AB - Eleven men were administered placebo and three doses (0.12, 0.23 and 0.46 g of absolute alcohol per kg of body weight) of 50% alcohol (vodka) in a laboratory situation that provided both aggressive and nonaggressive response options. Two aggressive responses were available to subjects: the ostensible subtraction of money from a fictitious other person and the ostensible presentation of a loud noise to a fictitious other person. A nonaggressive monetary reinforced response was also available. Aggressive responding was elicited by the subtraction of money from the subjects which was attributed to the fictitious other person. Relatively low doses of alcohol (0.23 and 0.46 g/kg) increased aggressive monetary subtraction responses, but had no effect on decreased nonaggressive monetary reinforced responses. Thus, the observed increase in aggressive responding cannot be attributed to a generalized stimulant action of low alcohol doses. The increased aggressive responding was observed at blood alcohol levels well below those usually defined as intoxicating. It is suggested that responses to aggression-provoking situations can be altered by the consumption of the equivalent of one or two alcoholic drinks. PMID- 4033133 TI - Vulnerability to alcoholism in men: a behavior-genetic perspective. AB - The psychological and biological characteristics associated with the vulnerability to alcoholism are reviewed. The predisposing features can be accounted for on the basis of deviations in empirically established temperament traits, thereby supporting the viability of a behavior-genetic perspective for elucidating the susceptibility to alcoholism. The temperament perspective also has heuristic value for improving our understanding of the neurobiological mechanisms that link the genetic predisposition to overt behavior. In addition, the temperament approach has ramifications for the prevention and treatment of alcoholism, as well as for clarifying the etiology and classification of certain other psychiatric disorders. The questions of what may be inherited in alcoholism and how this information can be usefully applied to enhance our knowledge of alcoholism etiology, prevention and clinical management are addressed. PMID- 4033134 TI - Blood platelet uptake of serotonin in men alcoholics. AB - Blood platelet uptake of 3H-serotonin (5HT uptake) was determined in a group of inpatient alcoholics who had just undergone detoxication (N = 19) and an age matched group of nonalcoholic controls (N = 19). Mean 5HT uptake was 18% lower in the alcoholics (p less than .01). A 3-min 5HT uptake of less than 6 pmoles/10(7) platelets identified 58% of the alcoholics, but only 15% of the controls had a 5HT uptake lower than this value. These results support the hypothesis that serotonergic dysfunction may exist in alcoholics. PMID- 4033135 TI - [Differential voltametry: a new method for studying the cerebral metabolism of monoamines]. AB - In vivo electrochemistry by differential pulse voltammetry represents an interesting option for functional neurochemistry or neuropharmacology. This paper successively presents the principle of the method and the technical bases of the measurement. The particular points of the specificity of the method and the necessary identification procedure of the different species detected in vivo are discussed (see fig. 1 to 7) with special reference to the detection of ascorbic acid and catechol compounds. Success for analysis of 5-hydroxy-indolic compounds are also referenced. In a second part of the paper an example of an in vivo metabolic exploration is presented. The detection of a catechol compound in the rat locus coeruleus, its identification as being extracellular DOPAC, its origin in noradrenergic cell bodies, its relationship with the activity of this group of noradrenaline containing perikarya are discussed (see fig. 8 to 15). PMID- 4033136 TI - An in vivo model for pharmacokinetic studies in the kidney. AB - In order to assess drug renal kinetics in vivo, the two kidneys of seven ewes were surgically placed under the skin. Through the use of renal function tests and a series of biopsies, we found that the kidneys remained normal in their subcutaneous location. Gentamicin renal kinetics were evaluated in conscious animals by a series of biopsies. Histological controls showed only slight lesions due to biopsy; based upon plasma hydrocortisone concentration, there was no indication of chronic stress affecting the renal pharmacokinetics. We suggest that this model has great potential as a method for studying in vivo the kinetics of drug disposition in the renal tissue and assessing the residue level of a drug. PMID- 4033137 TI - A rat model for the study of transplacental pharmacokinetics and its assessment with antipyrine and aminoisobutyric acid. AB - The suitability of a pregnant rat model for the study of transplacental pharmacokinetics was assessed by two test agents, antipyrine, which freely equilibrates in the maternal and fetal blood, and aminoisobutyric acid, which is actively transported from mother to fetus. In accordance with an ideal protocol for a two-compartment model solved for bolus injections, unlabeled antipyrine was injected into the mother (day 20 of gestation), and labeled antipyrine was injected into its fetuses following exteriorization under ether anesthesia. Maternal and fetal blood samples (2-3 fetuses removed at each time period) were collected sequentially under brief periods (2-3 min) of ether anesthesia up to 9 12 hr. In separate studies it was found that sequential removal of fetuses did not significantly alter maternal or fetal serum drug concentrations. As expected, placental clearances (ml/h-1/kg-1) of antipyrine from mother to fetus (392 +/- 86) and from fetus to mother (448 +/- 107) did not significantly differ. As an alternate approach, (3H)aminoisobutyric acid was either injected into the mother or into the fetuses, and maternal and fetal blood samples were sequentially collected in each case; the clearance of this agent from fetus to mother was 53 ml/h-1/kg-1, and, as expected, was much lower than that from mother to fetus (168 ml/h-1/kg-1). It is suggested that the pregnant rat model can be used as a substitute for the chronically catheterized pregnant sheep model for the study of pharmacokinetics in the maternal-fetal unit. PMID- 4033138 TI - Evaluation of microwave irradiation technique to quantitate acetylcholine in the diaphragm. AB - This report evaluates rapid enzyme inactivation prior to acetylcholine quantitation in the diaphragm. Methods of sacrifice were decapitation and microwave irradiation. Six-hundred millisecond exposure to microwave irradiation was sufficient to raise diaphragmatic temperature to 91 degrees C and inactivated 90% of the acetylcholinesterase enzyme. The acetylcholine content of the diaphragm was found to be 3.0 nmol/g, independent of the method of sacrifice. The postmortem changes observed in brain acetylcholine content following decapitation did not occur in the diaphragm. PMID- 4033139 TI - Measurement of human small airway smooth muscle function in vitro with the bronchiolar strip preparation. AB - The technique by which human bronchiolar strips are prepared is described in detail. The biological viability of the preparations after storage at 4 degrees C overnight and the reproducibility of contractile responses to KCl and methacholine were examined in lung tissue from six patients. Measurements were performed on the first and second day after surgical resection. On both days, most bronchioles showed an increase in contractility. The responses on the first day were not different from those on the second day. No significant changes in time were found for pD2 and slope of the methacholine dose-response curves. The variability of responses between patients was significantly larger than between strips within patients. The pD2 was the best reproducible parameter. PMID- 4033140 TI - An inexpensive apparatus for simultaneous automatic measurement of oxygen consumption in six small laboratory animals. AB - A closed-circuit system for the simultaneous measurement of oxygen consumption in six small laboratory animals is described. The system consisted of six glass chambers in a big water bath of constant temperature, an oxygen-supply unit, six pressure sensors, a microcomputer and a printer, or, optionally, a desk-top calculator. Ventilation within the chambers provided rapid equilibration of air temperature and humidity conditions. Easily sealing glass lids facilitated operation and maintenance of the system. Carbon dioxide was absorbed inside the chambers by soda lime. At 6-min intervals the consumed oxygen in each chamber was automatically replaced with oxygen from a low-pressure tank. The microcomputer, a self-constructed piece of equipment containing a Z 80 A central processing unit, received pressure data from the separately operating sensors, determined the decrements in chamber pressure due to oxygen consumption by the animal sitting in the chamber, and stored the calculated values in a 2 Kbyte RAM for outprint at the user's request. The apparatus proved to be sensitive, accurate, and easy to operate. PMID- 4033141 TI - An unanesthetized-gerbil model of cerebral ischemia-induced behavioral changes. AB - A surgical procedure has been developed to study the effects of cerebral ischemia in the unanesthetized Mongolian gerbil. The methodology is based upon the surgical isolation and instrumentation of both common carotid arteries. A loop of dental floss is placed around each carotid artery and passed through double lumen catheter material; this allows for later occlusion of the carotid arteries and their release in unanesthetized subjects. Functional changes following transient carotid artery occlusion are readily demonstrated by the occurrence of altered spontaneous locomotor activity at various times postischemia. This model should be useful in the evaluation of potential therapeutic agents in the treatment of cerebral ischemia. PMID- 4033142 TI - Calcium precipitation from mammalian physiological salines (Ringer solutions) and the preparation of high [Ca] media. AB - The maximum nonprecipitating concentration of calcium in a bicarbonate-buffered Krebs-Henseleit-type mammalian physiologic saline at 25 degrees C has been established as 10 mM in the presence of 1 mM phosphate, and as 18 mM when phosphate is absent. At 38 degrees C, the respective limits are 5.6 mM with the phosphate, and 16 mM in its absence. At its physiological concentration of 1.6 mM, calcium precipitation also appeared in solutions of pH greater than 9. When phosphate was present, the precipitate appeared immediately, but redissolved once pH was reduced below 7.8; in the absence of phosphate, precipitation of calcium carbonate became visible only after 3-4 min, but this precipitate would not redissolve even at pH 7.4. As carbonated stock bicarbonate solution gradually loses CO2 and becomes alkaline, a protocol for mixing physiologic salines using alkaline bicarbonate stock was developed. Calcium precipitation can be avoided if, before calcium is added, the bicarbonate-containing bulk solution is gassed with 5% CO2 for 15 min at a flow of 0.5 liter/min per liter of final solution. PMID- 4033143 TI - Method for quantitative operant response measurement during inhalation exposure. AB - A method for pharmacologic and toxicologic investigation of operant responses during inhalation exposure has been developed. The method was tested with rats. Toluene was utilized as a reference chemical. Toluene has been reported to cause significant increases in response rates of animals responding under operant schedules. A fixed interval schedule (F1-120 sec) was used. A significant increase in response rate was observed. Thus, the results indicated that the method was reliable and allowed operant schedule data to be obtained. The significance of this method lies in its versatility to allow an integrative study of operant response, inhalation kinetics, and pharmacologic action. Potential practical applications of the method include studies of the actions of drugs and chemicals administered via inhalation exposure. PMID- 4033144 TI - Data acquisition and analysis of hemodynamic signals using a standard microcomputer. AB - Hemodynamic drug-effect studies require repetitive measurements and time consuming calculations, particularly for the indices of left ventricular (LV) contractility and relaxation. To save time, we have created a system of acquisition, calculation, storage, and report of hemodynamic data processing E.K.G, peripheral arterial pressure, and LV pressure signals using a standard microcomputer (Apple II+) and simple accessory devices. The master program is written in BASIC Applesoft, with Mem/Dos as the disk operating system. A suite of utility routines, written in machine language, are used to program the A/D converter and to perform the vectorial calculations on the data. The software, written to process single-dose drug-effect studies, performs 1) data acquisition and storage as vectorial arrays accessible using BASIC, 2) monitor display, 3) calculations of the peripheral pressure and of the LV contractility and relaxation indices, 4) storage of the calculated indices, and 5) print-out of a report (curves and tables) at the end of each experiment and cumulated results of all the animals included in a protocol. The drawback of such a low-cost system is essentially the lack of available memory and the relatively slow speed of the microprocessor, which hinders simultaneous processing of indices needing nonlinear curve fitting and adequate print-out of protocols that are not single dose. PMID- 4033145 TI - Morphometric study of the interphase nucleus in some radiosensitive and radioresistant mammalian cells. AB - The radiosensitive cell populations, such as resting lymphocytes from thymus, spleen, lymph node and blood, have much smaller nuclei (Vn (nuclear volume) approximately 20 to 70 microns3) compared to radioresistant G0 cells from non lymphoid tissues (liver, kidney, brain, heart; Vn approximately 75 to 2700 microns3). It is suggested that radiation-induced disorganization of nuclear structures and cell pycnosis (interphase death) are promoted in G0 lymphocytes because in normal physiological conditions their nuclei assume a higher degree of chromatin condensation. In contrast, dispersion of chromatin into larger nuclear volumes, such as those of most non-lymphoid G0 cells, may hinder or delay radiation-induced cell death. PMID- 4033146 TI - Bio-informational equivalence. AB - Combined, the ideas of modern genetics and those of evolutionary process form the central explanatory concepts of biological science. Over the past 30 years or so, those concepts have merged with the idea that biological processes--at every level of organization--are equivalent to information transactions. The latter idea is here called the concept of bio-informational equivalence. It appears in one or other of three basic forms or else in some combination of them. According to the view adopted in this paper, bio-informational equivalence, in all its forms, has a deeply anthropocentric core which makes it unsuited for its present role as a quasi-theoretical perspective in biological science. PMID- 4033147 TI - Selection between multiple periodic regimes in a biochemical system: complex dynamic behaviour resolved by use of one-dimensional maps. AB - We analyse a model biochemical system in which two autocatalytic enzyme reactions are coupled in series, in conditions where multiple stable periodic regimes coexist for the same set of parameter values. We determine how the periodic regimes are reached from different initial conditions. The structure of the attraction basins is generally simple in the case of two coexisting limit cycles (birhythmicity). This structure and the associated behaviour may, however, become highly complex. In particular, the system exhibits enhanced sensitivity to initial conditions when the boundaries of the attraction basins are fractal. In the latter case, it becomes difficult to predict the evolution towards either one of two limit cycles, a phenomenon known as final state sensitivity. We show how these complex phenomena can be explained in a unified and simple manner by means of one-dimensional return maps derived from the time evolution of the model and from fifth degree polynomial equations. We suggest experimental tests of the sensitivity to initial conditions in chemical systems presenting birhythmicity. The physiological significance of the results is discussed with respect to the sensitivity of regulatory systems admitting multiple stable biological rhythms. PMID- 4033148 TI - Complementary spatial locations, width, and disparity. AB - An alternative analysis is offered for human depth perception in addition to the depth cue of disparity. The new analysis considers locations both proximal and distal to the fixation point and offers an explanation as to why a stimulus presented at one disparity sign may be mistakenly considered to possess the opposite sign. Three descriptions of applications, the Pulfrich phenomenon, an interpretation of the Hornbostel effect (the three-dimensional Necker cube), and the determination of the limits of stereoscopic vision, are discussed. In addition the new analysis discloses a particular advantage of binocular over monocular vision which had not been appreciated formerly. The new analysis offers a powerful analytical tool of simple mathematical form. The means of conversion from the new analysis to and from disparity is included. In addition the similarity between the new approach and the classical lens equation is examined. PMID- 4033149 TI - Investigation of protein refolding: a special feature of native structure responsible for refolding ability. AB - A possible origin of the refolding ability of globular proteins is discussed. It is shown that the structure of native proteins has a special feature, namely, that this is the only structure in which the short overlapping segments of the polypeptide chain are in one of the significantly stable conformations of the oligopeptides with the same amino acid sequences as segments themselves. It is shown that this special feature is responsible for the refolding ability of proteins. A simple formula is given for the estimation of the time, t, necessary for the spontaneous formation of a refolding nucleus by a certain segment and it is shown that the segment which has the smallest t value, will serve as a refolding nucleus. It is suggested that natural selection which ensures the maintenance of the native structure of globular proteins automatically results in the refolding ability of proteins regardless of the biological relevance of this ability. PMID- 4033150 TI - A diffusion Michaelis-Menten mechanism: continuous conformational change in enzymatic kinetics. AB - We present a simple model which extends the Michaelis-Menten mechanism by incorporating a continuous protein conformational change in enzymatic catalysis. This model can represent a quantitative version for "rack" or "induced fit" mechanisms. In the steady-state it leads to an equation of the Michaelis-Menten form, but with the catalytic step at the active site showing strong dependence on solvent viscosity. We suggest that a careful examination of solvent viscosity effects on enzymatic activity may serve as a test for the conformational change hypothesis. PMID- 4033151 TI - On the mathematics of digesta flow kinetics. AB - A unifying mathematical analysis of the use of compartmental models with and without time lags is given, with particular reference to the use of such models for digesta movement along the gastro-intestinal tract of the ruminant. First the generalized compartmental model without time lags is developed, and then it is shown how discrete time lags may be incorporated into this formalism. The important relationship between distributed lags, especially the gamma-distributed time lags, and the equivalent compartmental scheme, is emphasized. It is shown how distributed time lags can be included in a general compartmental model. The treatment covers, as special cases, some widely used models, and shows their relationship to each other and to other possible models. Finally a compartmental interpretation is outlined for a recently proposed double-exponential model. PMID- 4033153 TI - On the feeding strategy and the mechanics of blood sucking in insects. PMID- 4033152 TI - Neonatal heart rate variability and its relation to respiration. AB - The heart rate and respiration signals from nine healthy full term neonates were studied using autoregressive spectral analysis and cross-correlation techniques. The heart rate spectra could be divided into three regions of activity: a very low frequency (VLF) region from 0-0.04 Hz; a low frequency (LF) band from 0.04 0.20 Hz; and a high frequency (HF) region above 0.20 Hz. The newborns exhibited very little respiratory sinus arrhythmia in their heart rate variability in contrast to the situation for adults and older infants. However, variations in heart rate correlated strongly with changes in the breath amplitude, leading to what may be termed a breath amplitude sinus arrhythmia. The neonatal heart rate behaviour under stable conditions of oscillation could be simulated with a nonlinear control model provided the delay time in the baroreceptor loop of the model was taken to be approximately 2 seconds longer than in adults. This is consistent with the immature neurological status of neonates. PMID- 4033154 TI - Speculations on the origin of the ill-effects associated with the use of visual display terminals. AB - There are increasing reports of a wide variety of unexplained ill-effects associated with the occupational use of visual display terminals (VDTs); these include psychological complaints such as headache, irritability, and fatigue, musculoskeletal pains, dry or burning eyes, deteriorating eyesight, cataracts, facial dermatitis, and pregnancy abnormalities. Many VDTs emit near-ultraviolet (UV-A) radiation in amounts ranging from 200 to 1500 times less than the present U.S. safety standard of 1.0 X 10(-3) W/cm2. Although the possibility of a radiation hazard from VDTs is widely discounted, various points of circumstantial evidence are marshalled in this paper in support of the hypothesis that prolonged exposure to even these low amounts of UV-A radiation may result in progressive increases in sensitivity to UV-A and in cumulative biologic damage. It is further proposed that UV-A produces the ill-effects by catabolizing vitamin A in skin and plasma into highly active metabolites, the gradual accumulation of which results in an endogenous form of vitamin A intoxication. In addition to producing the skin and systemic effects of hypervitaminosis A, these metabolites presumably enter the fetal circulation, leading to pregnancy abnormalities similar to those associated with high doses of the vitamin for the treatment of skin disorders. PMID- 4033155 TI - The role of a reaction-diffusion system in the initiation of primary hair follicles. AB - A mechanism based on a reaction-diffusion system is proposed for the initiation of hair follicles in the epidermis during fetal development. It is demonstrated that initiation of primary follicles in a series of waves, within the proposed mechanism, is a consequence of the size and shape dependent properties of the reaction-diffusion system without the need for the propagation of signals through the skin. The observed trio grouping of follicles and variation of primary follicle density per unit skin area during development are also correctly predicted. An explanation, based on the reaction-diffusion system and the variation of its characteristic spatial wavelength with time during development, is suggested for the termination of both primary and secondary follicle initiation as well as follicle neogenesis. The proposed initiation mechanism is basically the same as that used to explain various spatial patterns observed in hair fibre formation (Nagorcka & Mooney, 1982). PMID- 4033156 TI - Autogenesis: the evolution of replicative systems. AB - Questions concerning the nature and origin of living systems and the hierarchy of their evolutionary processes are considered, and several problems which arise in connection with formerly developed theories--the autopoiesis of Maturana & Varela, the POL theory of Haukioja and the earlier developed evolutionary theory of Csanyi--are discussed. The organization of living systems, the use of informational terms and the question how reproduction can enter into their characterization, problems of autonomy and identity are included in the list. It is suggested that replication--a copying process achieved by a special network of interrelatedness of components and component-producing processes that produces the same network as that which produced them--characterizes the living organization. The information "used" in this copying process, whether it is stored by special means or distributed in the whole system, is called replicative information. A theoretical model is introduced for the spontaneous emergence of replicative organization, called autogenesis. Autogenesis commences in a system by an organized "small" subsystem, referred to as AutoGenetic System Precursor (AGSP), which conveys replicative information to the system. During autogenesis, replicative information increases in system and compartment(s) form. A compartment is the co-replicating totality of components. The end state of autogenesis is an invariantly self-replicating organization which is unable to undergo further intrinsic organizational changes. It is suggested that replicative unities--such as living organisms--evolve via autogenesis. Levels of evolution emerge as a consequence of the relative autonomy of the autogenetic unities. On the next level they can be considered as components endowed with functions and a new autogenetic process can commence. Thus evolution proceeds towards its end state through the parallel autogenesis of the various levels. In terms of applications, ontogenesis is dealt with in detail as an autogenetic process as is the autogenesis of the biosphere and the global system. PMID- 4033157 TI - Different modes of cell death and related phenomena: a proposal for a meaningful terminology in relation to tests of lethality. AB - The terms death (as an irreversible occurrence), necrosis and apoptosis are well defined and generally accepted in cell biology. Procedures and terminology related to estimation of different forms of cell mortality are, however, less clear and exact. Evaluation of the rate of mortality is important for numerous biological processes such as growth, atrophy, regeneration and neoplasia. Procedures used for assessing cell mortality include: 1. dye exclusion tests which were shown to be inadequate in apoptosis; 2. release of radioactive markers, also inadequate, as they occur also in life during shedding of membranes and cleavage of cell parts; 3. morphological and histochemical procedures which show only relatively late changes (autolysis) in cells which have not yet been completely obliterated; 4. absence of synthetic activities, which do not necessarily indicate death (e.g. mature erythrocytes); 5. colony forming capacity in cultures, which are considered by most authors as the most useful tests for assessing the effects of cytotoxic treatments. These tests do not, however, assess viability, but rather reproductive capacity. In all these tests, delayed changes in vitality can be determined by repeated or continuous testing. The following new terms are proposed and related to presently available tests. Aposchisis--for cleavage of cell parts not necessarily associated with cell death. N-mortality--for necrosis type of mortality estimated by the dye exclusion tests. A-mortality--for apoptosis type of mortality, which cannot be directly estimated at present. Acarpy--for loss of reproductive capacity of cells which is assessed by the colony forming tests. PMID- 4033158 TI - The coulombic hypothesis of mitochondrial energy transduction: a quantitative emendation. PMID- 4033159 TI - Sexual selection, handicaps and true fitness. PMID- 4033160 TI - Equilibrium energy analysis of freeze-fracture planes in membranes. AB - We have used equilibrium energy calculations to determine the most probable freeze-fracture planes in a lipid bilayer. Using a pairwise-summation computer method, we have generated numerical values for the Van der Waals potentials (electron shell repulsion, dispersion forces and electrostatic interactions) between molecules. We have compared our theoretical predictions with the experimental conclusion that the fracture planes occur normally between lipid molecules. These calculations also provide information about the composition of intramembranous particles, the potential for local clustering of single lipid types in the fluid membrane, and the importance of lipid molecules to the function of membrane proteins such as voltage-sensitive ion channels. PMID- 4033161 TI - Time-dependent interfacial charging effects of electrical fields applied to biological systems. AB - An important aspect of the interaction of a biological system with an externally produced electric field is that of charge separation and interfacial charging. This aspect has been ignored in some recent experimental and theoretical work. In the case of small regions of lower electrical resistivity imbedded in a higher resistivity medium, charge separation across the lower resistivity regions will result in charging of the interfaces between the lower and higher resistivity regions. The field produced by this charge separation will significantly affect the shape and the magnitude of the net electric field pulse within the lower resistivity regions. In particular, the field experienced by bone cells will be quite different from the externally produced field. The shape as well as the magnitude of the net electric field experienced by the cells depends on the time rate of change of the rising and falling phases of the externally produced electric field pulse. PMID- 4033162 TI - Evidence that lysolecithin is an important causal agent of atherosclerosis. AB - We examine the hypothesis of Portman et al. (1970) that lysolecithin is a causal agent of atherosclerosis. Four lines of argument support this hypothesis. (1) Lysolecithin is present, taken up and can act. Large amounts of lysolecithin are formed in plasma concomitant with triglyceride transport and it is readily taken up by arteries and retained for some time. Lysolecithin in aortic intima increases several-fold early in the induction of atherosclerosis in animals. From model system studies it is plausible that physiological doses of lysolecithin have physiologically significant effects. (2) At least one plausible mechanism of action can be formulated: stimulation of smooth muscle cell division due to lysolecithin-increased Ca2+ uptake. (3) The hypothesis is consistent with, and rationalizes, many literature observations in that inferred lysolecithin levels or production rates are appropriately correlated with a variety of positive and negative risk factors to a degree highly unlikely by chance. We found no data contradicting the hypothesis and only one piece weakening it. (4) A mechanism is outlined showing that low density lipoprotein receptor deficiency, the severest known risk factor, should cause the delivery of very high lysolecithin doses to artery walls. We conclude that the evidence, although indirect, is strong enough to give direct tests a high priority. PMID- 4033163 TI - Extracellular fields within the cortex. AB - A physically based theory of ionic currents associated with nervous activity is extended to provide a model of electrical activity in the cortex and its immediate neighbourhood. It is shown that the most significant variations of potential in the extracellular fluid are associated with fluctuations in density of calcium and potassium ions. Nervous activity may activate a calcium resonance at the external surface of a neural membrane, which in turn excites a potassium resonance. The resulting variations of electrical potential are sufficient to account for the event related potentials observed in the extracellular fluid. In addition, it is found that periodic variations of potential associated with the potassium resonance may be initiated by metabolic changes in ion concentrations and are in close correspondence with those identified experimentally with the alpha- and beta-rhythms. It is shown how to determine the effective conductance of the neural membrane from ionic theory, with a result comparable to that assumed by Hodgkin & Huxley, under the conditions of the voltage clamp. PMID- 4033164 TI - The uniqueness of protein sequences: molecular territoriality. AB - The number of tripeptides which do not occur and which occur only a small number of times in the existing data bank of protein sequences is much larger than that expected on the basis of random selection (from Monte Carlo analyses). Forty tripeptides are not found in the data bank of 289 500 amino acids while the value expected on the basis of random selection is 8.0 +/- 3.1. Seventy-one tripeptides occur only once with an expected value of 37.1 +/- 6.1. These results suggest that some peptides not found in certain species are reserved for use only in other species. The proposal is made that small peptides serve as species specific markers and function as signals in the recognition process for activation of the immune response. PMID- 4033165 TI - Optimization of error-correction processes with respect to time. Comparison to free energy aspects. AB - Time aspects of selection processes with the possibility of error correction through proofreading branches are studied by mathematical modelling of the kinetics of the reaction network. The methods are similar to those previously developed for free energy aspects. The minimum time delay that is necessary for achieving a certain accuracy level can then be calculated. The main difference to previous results lies in the initial association-dissociation step. In the free energy picture, this shall be essentially equilibrated, but that would yield a too large time delay in the time picture. Characteristic features that are indicative for the optimization strategy of the cell are discussed. PMID- 4033166 TI - A model for chromosome movement based on lateral interaction of spindle microtubules. AB - Quantitative morphological studies of meiotic spindles in the crane fly Pales ferruginea (Fuge, 1980, 1984, 1985) were the basis for the development of a model explaining anaphase chromosome transport in higher eukaryotes. Two main features of chromosome fibres were important for the model: (1) the existence of microtubules oriented obliquely with respect to kinetochore microtubules, and (2) a higher degree of disorder in fibres exerting a pulling force. It is postulated that microtubules of the same polarity being inclined to each other at a certain angle are able to slide past each other by means of mechano-chemically active side-arms working in alternate succession. Sliding is suggested to lead to a displacement of microtubules and chromosomes in direction towards the poles. Furthermore, it is suggested that the chromosome fibre in anaphase becomes progressively disintegrated by fragmentation and disassembly of microtubules. Fragmentation may be induced by bending stress within the dynamic system. PMID- 4033167 TI - Meso and racemic organisms and the transition to asymmetry. AB - In this paper we analyse extensive but previously unappreciated and scattered data on anomalous enzyme modulation by metabolite enantiomers for enzymes in the principle metabolic cycles and develop a coherent theory for their derivation from reciprocally coupled antipodal metabolisms in antecedent meso and racemic organisms. Structures for such chirally symmetric organisms are outlined, as is the gradual decoupling of their integrated antipodal metabolisms upon an evolutionary progression from meso organism to racemic organism to racemate of organisms. The driving forces and the dynamics for a transition to asymmetry are developed. PMID- 4033169 TI - Simple models do not eliminate complexity from the real world. PMID- 4033168 TI - Social selection in human populations: sufficient conditions for protection of deleterious alleles in a subdivided population. AB - Population dynamics of wild type (A1) and the deleterious genes (A2) under social selection have been studied by considering a subdivided population where the i-th subpopulation consists of Ni individuals with relative size ci (= Ni/sigma i Ni, i = 1,2, ..., n). A social selection model is constructed by assuming that the fitness of an individual is determined by its own as well as the parental phenotypes and that the number of migrants (M) from the ith subpopulation is divided equally into other subpopulations including the ith subpopulation itself. It has been shown that the gene frequency change depends on the loss of fitness of an individual due to the trait (gamma), an affected parent in the ith subpopulation (beta i), the probability that the heterozygote develops the trait (h), and the migration rates mi (= M/Ni). For 0 less than h less than or equal to 1, a sufficient condition for protection of the deleterious allele from extinction also depends on all of these parameters. However, when mi much less than 1 for all i, the condition is beta i less than gamma/(1 - gamma) for some i, whereas when mi much greater than h[gamma + beta i(1 - gamma)] for all i it is given by sigma i ci beta i less than -gamma/(1 - gamma). When h = 0, that condition is given by sigma ici beta i less than - gamma/(1 - gamma). Analyses also show that, when the deleterious alleles in a population are rare, the relative fitnesses of A1A1, A1A2, and A2A2 are given approximately by 1, 1-hS, and 1 - S, respectively, where S is the harmonic mean of Si = gamma + beta i(1 - gamma). Thus, under mutation-selection balance, the equilibrium frequency of deleterious alleles in the entire population is given by alpha/hS for 0 less than h less than or equal to 1 and square root alpha/S for h = 0, where alpha is the irreversible mutation rate from A1 to A2 in each generation. Population dynamics of rare deleterious genes under social selection can readily be studied by considering a finite population size. PMID- 4033170 TI - Heat shock proteins defend against intracellular pathogens: a non-immunological basis for self/non-self discrimination? PMID- 4033171 TI - A new view of pigmented neurons. PMID- 4033172 TI - Experiences with the Carpentier techniques of mitral valve reconstruction in 103 patients (1980-1985). AB - A total of 103 patients, age range 2 to 77 years, had some type of Carpentier reconstruction for mitral insufficiency. The mitral insufficiency resulted from ruptured chordae in 52, prolapse in 13, rheumatic fever in 16, coronary disease in eight, congenital disease in nine, and endocarditis in five. Multiple abnormalities were usually present. Four patients had severe calcification of the anulus. A reconstruction was accomplished in almost all patients. A ring annuloplasty was performed in all but two small children, but annuloplasty alone was adequate in only 17 patients. Fifty-eight had resection of 1 to 4 cm of diseased mitral leaflet. In 23 patients, chordal transposition or shortening was employed. Aortic leaflet repair was done in 28. Shortened, fused chordae (one to eight) were divided in 13 patients. Additional procedures performed in 28 patients included coronary bypass in 14. A successful repair was accomplished in all but one patient (moderate residual insufficiency). Two late hospital deaths were unrelated to the mitral repair. Following hospital discharge, ring dehiscence necessitated repeat operation in one patient. Thromboembolism produced a permanent minor neurological deficit in only one patient. There have been no late recurrences of insufficiency. Recurrent endocarditis necessitated valve replacement in three patients. A late Doppler evaluation of 95 patients for mitral insufficiency revealed none in 82, a trace in 12, and moderate insufficiency in one. Late catheterization in 16 patients revealed no insufficiency. The data suggest that reconstruction, rather than prosthetic valve replacement, can be successfully performed in over 90% of patients with nonrheumatic, noncalcified mitral valves. A much wider use of the technique seems strongly indicated. PMID- 4033173 TI - The use of muscle flaps in the repair of aortic defects. AB - The successful repair of an infected arterial anastomosis is often hampered by the need to leave prosthetic material at the site of infection. To determine whether an aortic defect could be repaired by direct closure with a muscle flap, thereby eliminating the need for prosthetic material, we subjected 33 young pigs weighing 17 to 19 kg to a left lateral thoracotomy under sterile conditions. An aortic defect 2 cm in diameter was created in the descending thoracic aorta just distal to the origin of the left subclavian artery. In one group (n = 11), this defect was patched with a freshly harvested but devascularized segment of chest wall muscle. In another group (n = 22), the aortic defect was patched with a vascularized chest wall muscle flap. Pigs were followed for up to 12 weeks and evaluated by arteriography and postmortem examination. There were no deaths or vascular complications attributable to the muscle flap repair in any pig. Pseudointimal formation began within 24 hours postoperatively and was of comparable thickness to the original arterial wall by 12 weeks. No aneurysmal changes were noted in any animal, and normal aortic luminal dimensions were preserved despite a tripling in mean body weight over the 12 week period. The loss of flap viability appeared to offer no threat to vascular integrity, as the free muscle patches, although undergoing cell necrosis and substantial remodeling, remained intact. These results demonstrate the short-term feasibility of using viable muscle flaps to patch aortic defects in situations wherein the use of prosthetic material would be undesirable. PMID- 4033174 TI - Chest wall tumors. Experience with 100 consecutive patients. AB - One hundred consecutive patients with chest wall tumors undergoing resection during the past 8 years were reviewed. There were 55 female and 45 male patients with ages ranging from 12 to 84 years (median 54.5 years). Fifty patients had primary malignant neoplasms, 32 had metastases, and 18 had benign tumors. The tumor was located in the ribs in 78 patients and in the sternum in 22. The number of ribs resected ranged from one to eight (median 3.4). Sternectomy was performed in 22 patients. Overlying soft tissue was resected en bloc in 47 patients. Reconstruction was with prosthetic material in 57 patients and autogenous ribs in 11. There were 100 muscle transpositions, including 45 pectoralis major, 33 latissimus dorsi, and 9 serratus anterior. Hospitalization ranged from 4 to 80 days (median 9.6 days). Complications occurred in nine patients. One patient required tracheostomy. There was one operative death. Median follow-up was 31.5 months. Recurrent tumor developed in seven patients. All patients with benign tumor and 95% of patients with primary tumor not previously treated were alive. However, only 41% of patients with metastatic tumor were alive. Metastases were responsible for 89% of late deaths. We conclude that aggressive resection for chest wall tumor with reliable reconstruction can be accomplished safely and that early wide resection is potentially curative treatment. PMID- 4033175 TI - Physiological rationale for a bidirectional cavopulmonary shunt. A versatile complement to the Fontan principle. AB - The original Fontan procedure included a classic superior vena cava-to-right pulmonary artery (Glenn) shunt. Subsequent experience demonstrated that this anastomosis was not essential and was an unnecessary commitment of the larger right pulmonary circulation to the smaller blood volume of the superior vena caval return. With application of the Fontan principle to more complex cardiac malformations, there has been a reconsideration of possible benefits of a cavopulmonary shunt in selected patients. A modified shunt from the divided end of the superior vena cava to the side of the undivided right pulmonary artery utilized in 21 patients is described. This shunt is designed to allow bidirectional pulmonary arterial distribution of both superior vena caval inflow and right atrial outflow after completion of the Fontan procedure. Twelve patients had the bidirectional shunt performed prior to a Fontan operation; five of these had a subsequent atriopulmonary connection and seven await operation. Eight patients had construction of this shunt at the time of their Fontan procedure. One patient had a bidirectional shunt constructed following atriopulmonary anastomosis to help relieve right atrial outflow obstruction. Two patients with univentricular heart undergoing simultaneous Fontan procedure and a bidirectional shunt died while in the hospital. The remaining 19 patients have been followed up for 2 months to 9 years with one late sudden death at 9 years. There have been no bidirectional cavopulmonary shunt failures, stenoses, kinks, or recognized pulmonary arteriovenous malformations. Postoperatively, eight patients had assessment of pulmonary distribution of shunt blood flow by angiography. Seven of these patients were also evaluated by radionuclide angiography. Superior vena caval blood flow via the bidirectional cavopulmonary shunt tended to be greater to the right lung, but bilateral pulmonary flow was documented in all but one patient. After Fontan operation, six of seven patients tested also demonstrated bilateral distribution of atriopulmonary flow. We concluded from our experience that this modified shunt provides excellent relief of cyanosis, allows bidirectional pulmonary distribution of both superior vena caval return and also the right atrial blood flow after atriopulmonary connection, and may be done before, with, or after a Fontan procedure and is compatible with all currently recommended modifications. Perioperative hemodynamic adjustments to the Fontan procedure may be improved by reducing atrial volume, and this may also be of potential benefit in the long-term adaptation to Fontan physiology by minimizing atrial distention. PMID- 4033176 TI - Modified Blalock-Taussig shunt following long-term administration of prostaglandin E1 for ductus-dependent neonates with cyanotic congenital heart disease. AB - In the treatment of cyanotic heart diseases in neonates who are ductus dependent, the small size of the pulmonary artery and/or subclavian artery often precludes construction of a sufficient Blalock-Taussig shunt. To avoid an emergency operation and to obtain pulmonary and subclavian arteries of adequate size (3 mm), a low dose of prostaglandin E1 was given to 16 neonates for a mean of 47 days (range 26 to 65 days), and a modified Blalock-Taussig shunt operation was performed in neonates whose mean age was 50 days. The pulmonary artery grew significantly (mean 4.5 mm) and the mean diameter of the subclavian artery was 3 mm, which was large enough for a good shunt at the time of operation. There were two late deaths and one operative death. All surviving patients shunts at the mean follow-up period of 22 months. The shunt was constructed on the same side as the ductus arteriosus so that the ductus could be ligated at the same operation in selected cases; the ductus may not close after discontinuation of prostaglandin E1 infusion and may cause uncontrollable congestive heart failure because of excessive pulmonary blood flow, particularly in patients with a univentricular heart. The ductus, dissected in nine patients, was enlarged and elongated in all and was ligated in four patients without complication. PMID- 4033177 TI - Acute control of pulmonary regurgitation with a balloon "valve". An experimental investigation. AB - Operations for certain congenital cardiac lesions can produce pulmonary regurgitation. Pulmonary regurgitation contributes to right ventricular dysfunction, which may cause early postoperative morbidity and mortality. To ameliorate the problems of pulmonary regurgitation during the early postoperative period, we evaluated a method for its acute control. Complete pulmonary valvectomy was performed utilizing inflow occlusion in eight sheep. A catheter with a 15 ml spherical balloon was positioned in the pulmonary arterial trunk; its inflation and deflation were regulated by an intra-aortic balloon pump unit. Blood flow from the pulmonary arterial trunk and forward and regurgitant fraction were determined from electromagnetic flow transducer recordings. The regurgitant fraction with uncontrolled pulmonary regurgitation was 38% +/- 3% (forward flow = 42 +/- 5 ml/beat and regurgitant flow = 16 +/- 2 ml/beat). Inflation of the balloon during diastole was timed to completely eliminate pulmonary regurgitation. This balloon control of pulmonary regurgitation increased pulmonary arterial diastolic pressure from 12 +/- 1 to 17 +/- 1 mm Hg (p less than 0.0001) and decreased pulmonary arterial systolic pressure from 31 +/- 3 to 27 +/- 1 mm Hg (p = 0.06). Pulmonary arterial pulse pressure decreased from 19 +/ 3 to 9 +/- 1 mm Hg (p less than 0.003). Elimination of pulmonary regurgitation decreased right ventricular stroke volume (25 +/- 3 versus 42 +/- 5 ml/beat, p less than 0.0002) and resulted in a 46% reduction in right ventricular stroke work (5.0 +/- 0.6 versus 9.4 +/- 1.0 gm-m/beat, p less than 0.001) with no change in net forward pulmonary artery flow. Thus, acute pulmonary regurgitation can be controlled and this control improves overall hemodynamic status and decreases right ventricular work. PMID- 4033178 TI - A surgical technique for correction of total anomalous pulmonary venous drainage. AB - A technique was employed successfully for correction of total anomalous pulmonary venous drainage into the upper right superior vena cava. A J-shaped right atriotomy was performed; the posterior flap was sutured to the anterior border of a previously enlarged atrial septal defect. The right superior vena cava was divided above the site of drainage of the pulmonary veins, and its proximal opening closed with a suture. The pulmonary venous return was directed to the left atrium in this way. The right atrial-right superior vena caval continuity was then reestablished by an anastomosis between the previously opened right atrial appendage and the distal end of the right superior vena cava. Finally the remaining atriotomy was closed. The azygos vein must be ligated to avoid systemic unsaturation. For correction of anomalous pulmonary venous drainage into the azygos vein with this technique, ligature of the azygos vein must be placed distally to the site of anomalous drainage. Three patients, aged 2 months, 7 years, and 16 years, respectively, with different anatomic types of the anomaly, were successfully operated on with this procedure. Findings displayed from the postoperative hemodynamic, echocardiographic, and clinical evaluation are encouraging, after a follow-up period that ranges from 4 months to 4 years. The advantages of the repair are discussed. PMID- 4033179 TI - Permanent cardiac pacing after the Fontan procedure. AB - Permanent cardiac pacing after a Fontan procedure is complicated by complex cardiovascular anatomy. Of 332 patients undergoing the Fontan procedure at the Mayo Clinic, we evaluated 15 who postoperatively required permanent pacing (mean age 16.5 years, range 4 to 31 years). Underlying congenital cardiac defects included univentricular heart in nine patients, double-outlet right ventricle in three, and tricuspid atresia in three. The indication for pacing was postoperative heart block in seven patients, congenital heart block in five, postoperative sick sinus syndrome in two, and heart block because of previous operation in one. Pacemakers were implanted immediately postoperatively in 11 patients and 12 to 57 months later in four patients. VVI systems were used in nine patients, DDD in four, AAI in one, and a Medtronic Activitrax VVI in one. All ventricular leads were epicardial. Four atrial leads were transvenous endocardial and one was epicardial. Three patients died 4, 9, and 69 months later of causes unrelated to pacing. Among the 12 survivors, mean follow-up was 34 months (range 1 to 107 months). Two patients had a total of three episodes of loss of ventricular capture because of increased chronic thresholds. Our current approach to pacing after a Fontan procedure includes (1) intraoperative placement of temporary atrial and ventricular electrodes, (2) intraoperative attachment of a permanent ventricular epicardial lead for congenital or surgically induced high grade atrioventricular block, (3) postoperative insertion of transvenous atrial leads if dual-chamber pacing is indicated, and (4) use of programmable pulse generators with high output capability. PMID- 4033180 TI - Two-dimensional echocardiography in dogs. Variation of left ventricular mass, geometry, volume, and ejection fraction on cardiopulmonary bypass. AB - Quantitative two-dimensional echocardiography was evaluated in 39 open-chest dogs placed on cardiopulmonary bypass. The correlation coefficient of left ventricular end-diastolic volume against postmortem pressure-volume curves was r = 0.89 to 0.93 (347 measurements in 15 dogs, 0 to 24 mm Hg). Ejection fraction was validated against roller pump flow and echo left ventricular end-diastolic volume (r = 0.83, n = 13). Left ventricular mass in vivo was compared with postmortem left ventricular mass (r = 0.81 in 21 early studies, r = 0.91 in 10 later studies with updated equipment) and was found to increase with ischemic injury as well as cardiopulmonary bypass with hemodilution. Left ventricular mass increased (p less than 0.001) from 119 +/- 5 (standard error of the mean) to 138 +/- 6 gm (n = 23) after 2 1/2 hours on cardiopulmonary bypass and moderate hemodilution. With the addition of ischemic arrest, left ventricular mass increased from 119 +/- 7 to 148 +/- 11 gm (p less than 0.01, n = 8), and myocardial water content increased by 2.0% +/- 0.4%, which accounted for at least 65% of the observed mass change. Mean left ventricular wall thickness increased from 13.8 to 15.5 mm (p = 0.02) after ischemia. Ventricular shape became more spherical with increasing left ventricular end-diastolic pressure. We conclude that two-dimensional echocardiography can be reliably used for accurate, serial measurements in physiological studies. The demonstrated variability in left ventricular mass is important, yet frequently ignored. Recognizing left ventricular mass changes may facilitate the detection of myocardial injury reflected as edema. PMID- 4033181 TI - Pulmonary artery thrombosis associated with anomalous pulmonary venous connection: an unusual complication following the modified Fontan procedure. AB - The presence of unrecognized partial anomalous pulmonary venous connection may cause complications of pulmonary infarction and right-to-left shunting in patients undergoing the modified Fontan procedure. These complications can be prevented by identification of any anomalous pulmonary venous connection at preoperative cardiac catheterization. PMID- 4033182 TI - Cor triatriatum and total anomalous pulmonary venous connection: a rare, surgically correctable anomaly. AB - Two cases of a very uncommon congenital association (cor triatriatum and total anomalous pulmonary venous connection) are presented. This association should be suspected in any infant with signs of pulmonary venous obstruction. PMID- 4033183 TI - Coarctation of the aorta: a new surgical technique. AB - We developed a new surgical technique to treat coarctation of the aorta. It consists of an aortoplasty in which the left subclavian artery is transected, opened longitudinally, and sutured to the coarctated segment so as to correct the narrowing and also maintain blood flow through the left upper limb. PMID- 4033184 TI - Treatment of chylothorax. PMID- 4033185 TI - Complications of left atrial catheter. PMID- 4033186 TI - Papaverine treatment of vein grafts. PMID- 4033187 TI - Further studies on the use of the fluorescent retrograde tracer True Blue in combination with monoamine histochemistry. AB - Some basic methodological aspects on the use of the retrograde fluorescent tracer True Blue (TB) was studied in freeze-dried material in the rat CNS. On the basis of fluorescence morphology and intensity at different filter settings it was possible to objectively delineate 3 distinct zones of the TB injection site, and define degrees of retrograde labelling from the different zones. Correlative studies of injection sites in subportions of the spinal cord and retrograde labelling in cell bodies of defined nuclei in the brainstem and cortex showed that effective uptake occurred only from the central area of the injection (zone I), while the uptake from the less intensely fluorescent zone II was variable and could only be documented for systems terminating within this zone. Time-course studies revealed that the size of the injection site and the resulting retrograde labelling is stable up to at least two months after injection and that relatively long survival times are often needed for optimal labelling. For practical purposes a bulk transport velocity of 20 mm/day can be used for estimating the survival time required for reasonable retrograde labelling. The accumulation of TB did not interfere with the visualization of monoamines in the same neurones, and the tracer was never seen to be anterogradely or transcellularly transported. PMID- 4033188 TI - A method for microscopic studies of cerebral angioarchitecture and vascular parenchymal relationships, based on the demonstration of 'paravascular' fluid pathways in the mammalian central nervous system. AB - A new method is described for morphological studies of blood vessels and related cellular elements in the mammalian central nervous system (CNS). The tracer protein, horseradish peroxidase (HRP), in solution, is infused intraventricularly or intracisternally in anesthetized animals over 5-10 min. During this period, HRP in the subarachnoid space enters the perivascular spaces around penetrating arterioles and rapidly permeates the gliovascular basal laminae surrounding capillaries. After fixation by intravascular perfusion of aldehydes, brain sections are incubated with the highly sensitive chromogen, tetramethylbenzidine. Intraparenchymal blood vessels throughout the CNS are vividly demonstrated for light microscopy by HRP reaction product in their perivascular spaces or basal laminae. Correlative ultrastructural investigations of specific blood vessels and related parenchymal elements can be conducted using adjacent sections. PMID- 4033189 TI - An oscilloscope spot intensifier, to improve photographic recordings of action potentials. AB - A circuit diagram is shown for a semiconductor device to intensify the brightness of an oscilloscope during the rapidly rising and falling phases of signals such as action potentials. Brightening pulses proportional in amplitude to the rate of change in the Y-axis are available for connection to an oscilloscope with an external intensity ('Z') modulation input. The circuit requires one transistor, one dual operational amplifier and two single fast operational amplifiers. PMID- 4033190 TI - Formalin test in mice, a useful technique for evaluating mild analgesics. AB - A modification of the formalin test appropriate for testing of mice is described. Formalin 1 or 5% was injected into the dorsal surface of a hindpaw, and the time the animal spent licking the paw was recorded. On the basis of the response pattern, two distinct periods of intensive licking activity were identified; an early (0-5 min after injection) and a late response (20-30 min after injection). The following analgesics were investigated (dose range): acetylsalicylic acid (100-400 mg/kg), paracetamol (100-400 mg/kg) and morphine (0.6-10 mg/kg). Acetylsalicylic acid (200-400 mg/kg early response, 300-400 mg/kg late response), paracetamol (200-400 mg/kg early response, 300-400 mg/kg late response) and morphine (2.5-10 mg/kg) inhibited the responses in a dose-dependent manner. The results indicate that the test is useful for evaluating mild analgesics. It may have advantages over some of the tests that are commonly used for testing analgesics. PMID- 4033191 TI - A baseline stabilizer for electrophysiology. AB - We describe a circuit that compensates for a slowly drifting baseline without distorting the signal of interest. Implementation of this non-linear filter is quite simple; total cost of components is less than $20.00. The baseline stabilizer should be especially useful for intracellular recording and for recording evoked surface potentials. PMID- 4033192 TI - A simple statistical test for the vertex ratio using Monte Carlo simulation. AB - The vertex ratio is the crucial quantity in vertex analysis, which is a method to characterize the mode of growth of neuronal tree structures (i.e. dendrites and axons). In this report we propose the use of the Monte Carlo test to calculate a level of significance for the vertex ratio. As a result the vertex ratio can be used to analyse neuronal trees with respect to a range of growth hypotheses, including terminal and segmental growth. PMID- 4033193 TI - Postmastectomy lymphedema. PMID- 4033194 TI - Effect of increased systemic venous pressure on thoracic duct and peripheral lymph flow in dogs. AB - In congestive heart failure, lymph flow from the cannulated thoracic duct is greatly increased. However, there has been scant data on lymph flow in the intact lymphatic system with systemic circulatory congestion. In the present study, thoracic duct and peripheral lymph flow were qualitatively determined using heated cross-thermocouples in seven mongrel dogs. Central venous pressure was raised artificially by infusing large volumes of crystalloid solution equivalent to a maximum of 30% of body weight. Although both thoracic duct and peripheral lymph flow increased with an intact (closed) lymphatic system, the increase was notably less than with a transected (opened) cervical thoracic duct. With systemic circulatory congestion, cannulated thoracic duct lymph flow circumvents a major lymph impediment to lymph flow (i.e. high central venous pressure) and therefore considerably overestimates in vivo central lymph flow in this condition. PMID- 4033195 TI - The mobile pneumatic arm sleeve: a new device for treatment of arm lymphedema. AB - A new simple and inexpensive device for treatment of upper limb lymphedema is described. Two days of application (approximately 12 hours) in 20 patients who otherwise maintained normal activities achieved a mean reduction of 21% of tissue swelling. PMID- 4033196 TI - Macromolecular transport. PMID- 4033197 TI - Effect of terbutaline on peripheral lymph flow, protein concentration and transport, and edema formation after thermal injury in rabbits. AB - In the rabbit, intraarterial infusion of 5 micrograms/min of terbutaline within the first two hours after moderate thermal injury prevents edema and reduces augmented lymph flow, lymphatic protein transport, and tissue fluid protein concentration. Terbutaline, however, fails to prevent edema 4 hours after thermal injury although the increase of leg volume (24%) is less than in the untreated, burned control leg (56%). A higher dose of terbutaline (15 micrograms/min) also fails to block edema 4 hours after burning and its effect on leg volume, lymph flow, and lymphatic protein concentration is similar to that of 5 micrograms/min infusion. Terbutaline does not alter the extent of tissue injury after burning as the increase in tissue fluid lactic dehydrogenase and potassium are similar with "treated" and "untreated" burns. PMID- 4033198 TI - Retinal edema in patients with generalized primary lymphedema. PMID- 4033199 TI - Primary lymphedema of the leg: relationship between subcutaneous tissue pressure, intramuscular pressure and venous function. AB - In eight patients with unilateral primary lymphedema, subcutaneous tissue and intramuscular pressure were measured in both legs using the slit-catheter technique. Venous function was assessed by venography, or Doppler or photoplethysmography. Both at rest and during exercise, subcutaneous tissue pressure was elevated in the lymphedematous leg (17.9 +/- 7.6 and 33.0 +/- 10.8 mmHg respectively) compared to healthy contralateral leg (0.4 +/- 2.6 and -0.6 +/ 3.6 mmHg; p less than 0.001). The intramuscular pressure in the anterior tibial compartment was also increased at rest and during exercise in the edematous leg (24.9 +/- 4.4 mmHg and 43.6 +/- 11.2 mmHg respectively) compared to control leg (9.6 +/- 5.6 and 25.8 +/- 10.00 mmHg). These findings suggest that derangements in both the superficial and deep lymphatic systems as well as venous dysfunction contribute to the clinical appearance of "primary lymphedema." PMID- 4033200 TI - Lymph vessels of the rabbit heart: distribution and fine structure in ventricles. AB - We examined the distribution and fine morphology of small lymph channels in the rabbit heart, and particularly in the ventricular myocardium. Light microscopy showed many small subendocardial lymphatics in both ventricles and especially in the subendocardium of papillary muscles and right side of the septum. Electron microscopy revealed that the endothelial ultrastructure of these lymphatics was similar at different sites. The cytoplasm exhibited frequent adluminal expansions and contained numerous micropinocytotic vesicles opening both into the lumen and surrounding interstitium. Bundles of microfilaments, commonly arranged in a parallel fashion, were also visible. Between laminations of the endothelial wall were relatively dense, finely granular material. Intercellular contacts were characterized by cell superimpositions and interlockings, specialized junctions and occasionally maculae adherentes. The basal membrane was discontinuous and often of variable thickness. In the surrounding connective tissue, thin filaments appeared adjacent to the abluminal surface of the endothelial wall. Although the fine structure of the walls of small lymphatics in the rabbit ventricular myocardium was similar to that of small lymphatics at other sites, their distribution varied from other mammalian species. PMID- 4033201 TI - Magnesium and liver cirrhosis: a hypothesis. AB - Low serum, cerebrospinal fluid, erythrocyte, muscle and bone Mg concentrations have been found in liver cirrhosis, indicating a Mg deficiency. Decreased intake, fat malabsorption, renal tubular acidosis and increased serum levels of aldosterone, growth hormone and glucagon could be the causative factors. PMID- 4033202 TI - Early radiation-induced proctosigmoiditis responds to magnesium therapy. AB - A group of 10 patients with cervical carcinoma with early radiation-induced proctosigmoiditis and low serum Mg levels was treated with low residue diet and antidiarrheals. The diarrhea cleared within a period of 2-6 weeks. A second group of 10 patients with hypomagnesemia was treated with intravenous infusion of Mg sulfate for 3 consecutive days. The diarrhea disappeared by the end of treatment, paralleling normalization of serum Mg levels. PMID- 4033203 TI - Electrolytes and ventricular arrhythmias. AB - Magnesium concentrations in the blood plasma of patients with ventricular arrhythmias were found to be significantly lower than in controls, whereas the sodium and calcium concentrations of the erythrocytes were significantly higher than in the controls. Intensive magnesium therapy resulted in an increase of the plasma magnesium concentration and in significant changes of Na, K, Ca and Mg in the erythrocytes. By means of long-term ECG recordings, it was shown that the therapy may result in a quantitative decrease of the ventricular arrhythmias. PMID- 4033205 TI - Magnesium level in drinking water and cardiovascular risk factor: a hypothesis. AB - Water hardness can no longer be considered as the most reliable "water factor' with regard to the cardiovascular risk observed in epidemiologic studies. Only two out of three studies have shown a reverse correlation between cardiovascular mortality and water hardness. But studies carried out on the water Mg level alone, as opposed to those on water hardness (Ca + Mg) have all shown a reverse correlation between cardiovascular mortality and the Mg level. In developed countries, the Mg intake is often marginal and the Mg intake coming from drinking water represents the critical factor through which the Mg intake is deficient or satisfactory. Thus, Mg deficiency, either experimental or in man facilitates cardiovascular pathology. The importance of the Mg intake in drinking water is both quantitative and qualitative. Water containing Mg is better and more quickly absorbed than dietary Mg. This particular availability might help to understand why an adequate water Mg level may determine a better state of health, even without any Mg deficiency. Epidemiological data in man and experimental data in rats have demonstrated that the intake of water containing a sufficient amount of Mg may prevent arterial hypertension and correlated ionic and nervous disturbances. Indirectly the water Mg level also interferes in the leakage of food-borne Mg during cooking. There is an inverse correlation between the Mg loss in the cooked food and the Mg level of the cooking water itself. Mg appears to be an antagonist of noxious polluting agents (e.g. in the human amnion, Mg is a competitive inhibitor of Pb and Cd). It is not advisable to enrich water in Mg in the course of the processing since its corrosivity index would also increase. The best pathway is probably to neutralize corrosive water by filtration on calibrated grains of earth-alkaline metals (Neutralite or Magno or Akdolit) to ensure the highest possible Mg/Ca ratio, with the best anticorrosive power. PMID- 4033204 TI - [Comparative effects of magnesium deficiency and overload on calcium and phosphorus metabolism in the growing pig]. AB - This study was designed to assess the influence of dietary magnesium on calcium and phosphorus metabolism in growing pigs. 18 4-month-old pigs received either an Mg-deficient (40 ppm), an Mg overload (5,600 ppm) or a control Mg diet (1,000 ppm) for 70 days. The following parameters were measured: kinetics of plasma concentrations of Ca, phosphates, Mg and alkaline phosphatase (AP), absorptions, urinary and fecal excretions, retentions of Ca, P and Mg, soft tissue and bone mineral contents (BMC), and intestinal mucosal CaBP (calcium-binding protein) and AP activities. Dietary Mg level had no effect on calcium and phosphorus metabolism as far as Ca and P absorptions and retentions, BMC, intestinal CaBP and plasma levels of Ca, P and AP are concerned. Mg overload significantly decreased urinary P excretion and increased kidney P content, but did not change fecal P excretion. Jejunal AP activity was slightly decreased in Mg-deficient pigs. The plasma, bone, urinary, fecal, absorbed and retained Mg varied linearly with Mg intake (r: 0,85-0.96). In Mg-deficient pigs, hypomagnesemia appeared after 1 week and its severity did not increase with time. In Mg-overloaded pigs, hypermagnesemia occurred very late and was limited. This suggests that, in the growing pig, dietary Mg has little or no effect on Ca-P metabolism. It may also be concluded that growing pigs are rather resistant to Mg deficiency since no clinical symptoms were observed. PMID- 4033206 TI - Observations on the article by Arsura et al.: Magnesium and zinc levels in ischemic heart disease, published in Magnesium 2: 105-112, 1983. PMID- 4033207 TI - [Synthetic progestational hormones and their principal indications in gynecology]. PMID- 4033208 TI - [Recto-sigmoidal complications of radiotherapy of cervical cancer (apropos of 92 cases)]. PMID- 4033209 TI - [Place of radiotherapy in the treatment of digestive lymphomas]. PMID- 4033210 TI - [Clinical and echocardiographic correlation in pure, severe and chronic aortic insufficiency]. PMID- 4033211 TI - [Viral hepatitis and pregnancy (apropos of 40 cases)]. PMID- 4033212 TI - [Neuropsychiatric forms of tuberculous meningoencephalitis]. PMID- 4033213 TI - [Epidural compression of the cervical spine and cauda equina by a malignant non Hodgkin's lymphoma]. PMID- 4033214 TI - [Management of fever during pregnancy]. PMID- 4033215 TI - [Carotid revascularization with a jugular graft in the rat]. PMID- 4033216 TI - O-acylated sialomucins in adenomatous and hyperplastic colonic polyps. PMID- 4033217 TI - Glucagon effect on the regeneration of ileal mucosa in rats after experimental desquamation of intestinal epithelium. PMID- 4033218 TI - The hepatotoxicity of mercury vapours in the light of biochemical, scintigraphic and morphological data. PMID- 4033219 TI - Non-thymic peptide complexes as immunobiologically active systems. Some properties of peptide complex system (PCS) of various origins. PMID- 4033220 TI - Production and evaluation of rabbit cholecystokinin (CCK). PMID- 4033221 TI - The effect of ethanol ingestion on plasma secretion and plasma cholecystokinin (CCK) in man. PMID- 4033222 TI - No release of GIP following intraaortic glucose infusion in anaesthetized rats. PMID- 4033223 TI - Pharmacokinetics of diazepam after intravenous, intramuscular and oral administration to humans. PMID- 4033224 TI - Rationale of garlic use in ischemic heart disease? PMID- 4033225 TI - Middle molecules. Myth or reality? PMID- 4033226 TI - Cytodiagnostics of pharyngeal tumours. PMID- 4033227 TI - Respect for sight and technological advances in ocular surgery. PMID- 4033228 TI - Human prostatic acid phosphatase. Molecular properties and clinical application. PMID- 4033229 TI - Treatment of renal cell carcinoma by in situ partial nephrectomy and extracorporeal operation with autotransplantation. AB - During a 10-year period, 33 patients underwent in situ enucleation, in situ partial nephrectomy, or an extracorporeal operation for low-grade (1 or 2), low stage (I or II), bilateral or solitary renal cell carcinoma. Only one patient (3%) (who had undergone in situ partial nephrectomy) had local recurrence; the projected 5-year rates of nonprogression of disease and survival from death due to cancer only were 76% and 87%, respectively. A group of patients who were closely matched for grade and stage of renal cell cancer underwent traditional transabdominal radical nephrectomy during the same time interval and had rates of nonprogression and survival similar to those of the conservative surgical group. Thus, in selected patients with low-grade, low-stage renal cell cancer, conservative surgical treatment (that is, renal parenchyma-saving procedures) can produce favorable results without the side effects (such as renal failure) associated with ablative renal operations. PMID- 4033230 TI - Myectomy for essential blepharospasm. AB - Essential blepharospasm is a progressive, bilateral, involuntary facial spasm. In this study, we conducted a prospective analysis of myectomy for the treatment of this condition in 21 patients. The procedure consisted of extirpation of the muscles that close the eyelids (protractors), which include the pretarsal, preseptal, and orbital components of the orbicularis oculi, as well as the procerus and corrugator supercilii muscles of the brow. In addition, the muscles that open the eyelids (retractors) were strengthened (by resection of the frontalis muscle and repair of disinsertion of the levator aponeuroses). The most common symptoms that necessitated myectomy were difficulty with driving (20 patients), watching television (17 patients), reading (15 patients), and eating (5 patients). Overall, the 21 patients had a 70% mean decrease in symptoms postoperatively. Five patients required an additional operation for management of residual blepharospasm. PMID- 4033231 TI - Sinus node dysfunction in pediatric and young adult patients: treatment by implantation of a permanent pacemaker in 39 cases. AB - To examine the clinical course of sinus node dysfunction that necessitates permanent pacing in the pediatric and young adult populations, we studied the records of the 39 patients 40 years of age or younger (mean age, 23 years) who underwent implantation of a permanent pacemaker for treatment of this disorder at our medical center between 1960 and 1983. The tachycardia-bradycardia syndrome was the most common rhythm disturbance, and syncope was the most frequent initial symptom. All symptomatic patients noted resolution of symptoms after pacemaker implantation. Twenty-five of the 39 patients (64%) had associated cardiovascular disease, most commonly transposition of the great arteries. In each of the 11 patients with this anomaly, sinus node dysfunction developed after a surgical procedure for correction of the defect. Of the total patient population, 20 patients (51%) had previously undergone a cardiac operation. The mean interval between pacemaker implantation and the previous operation was 105 months. After a mean follow-up of 50.5 months, the patients with no obvious underlying heart disease have done well. Each of the eight patients who have died had underlying cardiovascular disease. None of the deaths was thought to be pacemaker related. Sinus node dysfunction should be considered in the differential diagnosis of young patients with syncope or dizziness, especially if they have undergone a reparative cardiac surgical procedure. If symptomatic sinus node dysfunction is confirmed, permanent pacing is an effective therapeutic modality. In the absence of associated heart disease, the prognosis seems to be excellent. PMID- 4033232 TI - Age-dependent decline of natural killer and antibody-dependent cell mediated cytotoxicity activity of human lymphocytes is connected with decrease of their acid phosphatase activity. AB - Decline of cytotoxic potential of lymphocytes of aged persons in ADCC and NK cell mediated cytotoxic reaction was paralleled by a drop in the activity of acid phosphatase. Intensity of ADCC reaction and the level of acid phosphatase activity showed statistically significant correlation when these two parameters were measured in peripheral blood of the same persons. The role of acid phosphatase in cytotoxic function of lymphocytes is discussed. PMID- 4033233 TI - The relationship between sialic acid content and peanut agglutinin binding on senescent and enzyme treated human erythrocytes. AB - Young, old and neuraminidase treated human red blood cells (RBC) were investigated with peanut agglutinin (PNA), a lectin with a specificity similar to that of serum T-agglutinin. The effect of serum agglutinins on this interaction was also investigated. The density and distribution of PNA receptors were evaluated by agglutination with PNA and binding of ferritin-conjugated PNA (PNA F), or PNA labeled with radioactive iodine [( 131I] PNA). The results were correlated with the distribution of membrane bound sialic acids, as evaluated by chemical analysis and rate of agglutination with poly-L-lysine (PLL). Untreated RBC of all ages did not agglutinate with PNA and failed to bind PNA-F and [131I] PNA. Treatment of young RBC with neuraminidase, which resulted in reduction of membrane-bound sialic acids to an extent similar to that of physiologically aged RBC, resulted in the concomitant exposure of PNA binding sites and in the agglutination of these cells by autologous serum. Pretreatment of the neuraminidase treated RBC with autologous serum resulted in partial inhibition of the binding capacity of PNA on the RBC. The results indicate that the normal age related loss of sialic acids in circulating RBC is not identical with enzymatic removal of sialic acids by neuraminidase. The observations suggest that different mechanisms are functional in the recognition and sequestration of old RBC and of RBC treated with neuraminidase. PMID- 4033234 TI - Ontogenic variations in the interactions of lactate dehydrogenase isozymes with cellular structure. AB - The interactions of the LDH isozymes with cellular structure have been studied in the major tissues of the mouse during development. Overall, there is a clear indication that interactions between LDH and cellular structure are appreciable in all major tissues and at all stages of development, and an analysis of the isozyme status of the enzyme in both soluble and bound compartments has been effected. Information has been provided supporting the preferential binding of the A type activity to actin filaments. The data provided also support the concept of pelletable B type LDH in kidney and brain during the postnatal period. Binding was particularly extensive in the early embryonic stages, and the significance of this phenomenon, and the subcellular interactions observed to varying degrees in all the tissues throughout development, have been discussed in relation to the known metabolic characteristics of these separate tissue situations. PMID- 4033235 TI - A workplace health education program that reduces outpatient visits. AB - A workplace health education program aimed at reducing unnecessary outpatient visits was offered through 22 California employers. A total of 5,200 employees attended a presentation, received self-help books, and completed self administered questionnaires. All visits for their households were monitored for up to 15 months. The study utilized a quasi-experimental staggered intervention design involving eight different cohorts, before/after comparisons, with statistical adjustment for seasonality and other intervening variables. Visit rates for households insured only by Blue Cross of California were reduced by 17% (P = 0.001), or 2.0 visits per household per year. For all participants, the reduction was 7.2% (P = 0.06), or 0.8 visits. Reductions were seen for all age and educational strata. The program was most effective among households with first dollar fee-for-service insurance coverage. Households with insurance requiring co-payments had less reduction. No reduction was seen among health maintenance organization (HMO) members. The study concludes that a minimal cost, self-care workplace intervention can reduce outpatient visits by important magnitudes. PMID- 4033236 TI - Measuring clinical performance of individual internists in office and hospital practice. AB - No standardized methods exist for reliably measuring physicians' performance against clinically valid standards. In this study, statistically reliable peer review based on current national standards of internal medicine was used to evaluate the clinical performance of 66 internists in office and hospital practice. Evaluation was limited to the substantiation of diagnosis, prescribing indicated drug regimen, monitoring, and attaining expected patient response. Performance in substantiating diagnosis was better than in therapeutic management, and management in hospitalized patients was superior to office management. Superior performance by a physician was not consistent across diagnoses, but substandard office treatment in at least one diagnosis was associated with substandard office treatment in other conditions. Internists' performance was unrelated to their certification status but inversely related to the number of years since graduation from medical school. This method could be used to evaluate the effectiveness of continuing education in improving physicians' performance and to validate current examinations used in recertifying internists. PMID- 4033237 TI - Patient predictors of hospice choice. Hospital versus home care programs. AB - Research findings indicate cost savings associated with home care hospices, while hospital-based hospices can be as expensive as conventional care. Based on National Hospice Study data, this article identifies the characteristics of patients admitted to hospital-based and home care hospices in those areas of the country where a choice of hospice model was possible. Multivariate logistic regression indicates that the significant discriminating factors between the two patient populations relate to the availability of supportive care at home and the severity of nursing care problems at the time of hospice entry. Reinforcing selected pre-existing differences, an examination of prehospice had longer episodes of care than was the case for home care hospice patients. PMID- 4033238 TI - [Infectious endocarditis. 5 years' experience]. PMID- 4033239 TI - [Ultrastructural muscle study of chronic alcoholic patients with and without myopathy]. PMID- 4033240 TI - [Mycobacteriosis: presentation of 38 cases]. PMID- 4033241 TI - [Infectious endocarditis]. PMID- 4033242 TI - [Amanita phalloides poisoning. Diagnosis by radioimmunoassay and treatment with forced diuresis]. PMID- 4033243 TI - [Role of lipid changes as a risk factor in cerebrovascular ischemic accidents]. PMID- 4033244 TI - [Value of the electrophysiologic study of the diaphragm in the diagnosis of phrenic paralysis]. PMID- 4033245 TI - [Mediterranean lymphoma in a patient of advanced age]. PMID- 4033246 TI - [Lymphocyte subpopulations and the presence of abnormal proteins in plasma concentrates]. PMID- 4033247 TI - [The glioma-polyposis syndrome (Turcot's syndrome)]. PMID- 4033248 TI - [Sensitivity of the genus Streptococcus to 9 antibiotics]. PMID- 4033250 TI - [Arthrosis: a disease or aging?]. PMID- 4033249 TI - [Acute renal failure caused by iodinated contrast material]. PMID- 4033251 TI - [A classic problem: the diagnosis of pulmonary thromboembolism]. PMID- 4033252 TI - [Myocarditis in legionnaires' disease]. PMID- 4033253 TI - [Purpura fulminans in the adult. Presentation of 2 cases]. PMID- 4033254 TI - [Mammography and puncture biopsy in the diagnosis of breast cancer]. PMID- 4033255 TI - [Pulmonary oxalosis caused by Aspergillus niger]. PMID- 4033256 TI - [Pulmonary nocardiosis. Apropos of a case]. PMID- 4033257 TI - [Multifocal eosinophilic granuloma in an adult]. PMID- 4033258 TI - [Serum levels of amitriptyline and nortriptyline in a case of poisoning]. PMID- 4033259 TI - [Multiple cerebral infarctions as the 1st manifestation of systemic cancer]. PMID- 4033260 TI - [Cutaneous necrosis caused by vasopressin]. PMID- 4033262 TI - [Localized giant lymph node hyperplasia (Castleman's pseudotumor)]. PMID- 4033261 TI - [Pleural effusion of malignant etiology. Thoracoscopic use of talc as an effective method of pleurodesis]. PMID- 4033263 TI - [Tuberculin test: errors in injection and interpretation of the Mantoux test. Evaluation of a training course]. PMID- 4033264 TI - [Trapped lung syndrome. A rare cause of chronic pleural effusion]. PMID- 4033265 TI - [Useful data on parkinsonian syndromes]. PMID- 4033266 TI - [Agranulocytosis caused by glucantime (N-methylglucamine antimoniate) during treatment of kala-azar]. PMID- 4033267 TI - [Hepatitis caused by Q fever simulating acute cholecystitis]. PMID- 4033268 TI - [Association of allergic vasculitis and alcoholic liver cirrhosis]. PMID- 4033269 TI - [Leukocytoclastic vasculitis in liver cirrhosis]. PMID- 4033271 TI - [Visual evoked potentials in hepatic encephalopathy]. PMID- 4033270 TI - [Leukocytes labeled with 111In in the localization of abscesses]. PMID- 4033272 TI - [Intracellular calcium and renal function]. PMID- 4033273 TI - [Isotopic ventriculography (I). Global and segmental ventricular ejection fraction]. PMID- 4033274 TI - [Minimal blood levels of theophylline: circadian rhythm]. PMID- 4033275 TI - [Toxic megacolon in a patient with ulcerous proctitis]. PMID- 4033276 TI - [Enteroclysis or intestinal transit]. PMID- 4033277 TI - [Extrathoracic anthracosis]. PMID- 4033278 TI - [Bilateral partial convulsive crises associated with non-ketotic hyperglycemia]. PMID- 4033279 TI - [Haemophilus parainfluenzae endocarditis]. PMID- 4033280 TI - [Familial Mediterranean fever. Review of 16 cases]. PMID- 4033281 TI - [Neurologic manifestations in acute poisoning by organophosphorus insecticides]. PMID- 4033282 TI - [Calcitonin deficiency in postmenopausal osteoporosis]. PMID- 4033283 TI - [Usefulness of tiapamil, a new calcium antagonist, in the treatment of essential arterial hypertension]. PMID- 4033284 TI - [Usefulness of hepatic biopsy in fever of unknown origin]. PMID- 4033285 TI - [Non-Hodgkin's lymphoma with primary testicular manifestation. Presentation of 3 cases]. PMID- 4033286 TI - [A 34-year-old woman with metrorrhagia and abdominal pain (clinicopathologic conference)]. PMID- 4033287 TI - [Amiodarone and thyroid dysfunction]. PMID- 4033288 TI - [Primary hypothyroidism and secondary pituitary adenoma]. PMID- 4033289 TI - Use of quantitative ECG analysis for early detection and prediction of coronary heart disease. PMID- 4033290 TI - Precise reproduction of electrocardiograms by spline interpolation. PMID- 4033291 TI - Identification techniques applied to processing of signals from cardiovascular systems. PMID- 4033292 TI - Computerized system for isochronic epicardial mapping. PMID- 4033293 TI - Computer analysis of left ventricular pressure-volume relationships by echocardiography. AB - Programs were developed for the analysis of left ventricular pressure-volume relationships in clinical situations. Regression lines of end-systolic points on the pressure-volume plane were obtained from nine patients. Correlation coefficients between end-systolic pressure and volume were high. The indices calculated may be useful for diagnosis and research of left ventricular function. PMID- 4033294 TI - Computer-generated discharge letters in the coronary care unit. PMID- 4033296 TI - [Hemolytic activity of selected strains of the genus Yersinia]. PMID- 4033295 TI - Data systems in cardiological departments: an overview of the literature. PMID- 4033297 TI - [Hemolytic properties of strains of the genus Yersinia. II. Evaluation on liquid media]. PMID- 4033298 TI - [Hemolytic properties of strains of the genus Yersinia. III. Evaluation of bovine and horse blood]. PMID- 4033299 TI - [Capacity of strains of the genus Yersinia to produce enterotoxins evaluated by a test using suckling mice]. PMID- 4033300 TI - Effects of dantrolene sodium on occlusion and reperfusion arrhythmias in the canine heart. AB - The effects of dantrolene sodium on occlusion and reperfusion ventricular arrhythmias (VA) were studied in a canine model. Transient ischemia was induced by a 10 min occlusion period of the left anterior descending coronary artery in 27 control dogs and 32 dogs pretreated with dantrolene sodium (2.5 mg/kg). In the control group, 14 (52%) dogs experienced VA during occlusion. Five of these had ventricular fibrillation, 3 of which were fatal. Eight of 24 control dogs which reached reperfusion experienced ventricular fibrillation during the first 30 sec of reperfusion. Dantrolene sodium did not lower the frequency of VA during occlusion 22/32 (69%). Moreover, the incidence of fatal ventricular fibrillation during occlusion was significantly (p less than 0.025) higher in the drug treated group (12/32; 37.5%) than in the control group (3/27; 11%). Dantrolene sodium also significantly reduced the time that lasted from the commencement of occlusion to the appearance of ventricular fibrillation (240 +/- 1 sec versus 166 +/- 9 seconds, control and drug group, respectively p less than 0.05) without significantly altering either heart rate or blood pressure (169 +/- 4 b.p.m., and 170 +/- b.p.m.; 101 +/- 10 mmHg and 104 +/- 9 mmHg, before and after dantrolene sodium, respectively). These results indicate that dantrolene sodium might have an arrhythmogenic effect in the ischemic canine heart. PMID- 4033301 TI - Influence of urinary pH on pethidine kinetics in healthy volunteer subjects. AB - The kinetics of intravenous pethidine (150 micrograms kg-1) were determined in 10 healthy Caucasian subjects under uncontrolled and controlled (acidic and alkaline) urinary pH. Although large variations in the 48 hr urinary recovery of pethidine and norpethidine (26.9 +/- 5.9% & 23.4 +/- 4.6%, 0.6 +/- 0.3% & 3.6 +/- 1.6%, 6.9 +/- 3.2% & 17.4 +/- 6.6%, respectively, under acidic, alkaline and uncontrolled urinary pH were induced by change in urinary pH, the terminal t1/2 (7-8 hr), the AUC and the plasma concentration-time profiles were not affected. Under all these conditions, the disappearance of pethidine from the plasma was described by a triexponential function. A 3-compartment open model with input into the central compartment and elimination from both the central and the fast accessible (metabolising) compartment was proposed to interpret pethidine distribution in the body. This model explains the complimentary elimination of pethidine by renal excretion and metabolism. Under alkaline urinary pH, the hydrolytic route predominates as recovery of pethidine and norpethidine in the urine is significantly lower under this condition. Acidification of the urine may increase body clearance of the unchanged drug due mainly to greater renal clearance, and this may be useful clinically to treat acute pethidine poisoning and when the complimentary hepatic metabolism is impaired. PMID- 4033302 TI - Theophylline: a haemoperfusion modelisation. AB - A dynamic study of the kinetics of theophylline adsorption in aqueous medium by two adsorbent resins is proposed. The adsorption process involves Van der Walls pattern physical bonds. An in vitro haemoperfusion apparatus was schematized and data describing the adsorption-desorption process was obtained. A mathematical treatment led to the conclusion that first-order adsorption and desorption rates are involved, results which led to the consideration of a model of in vivo haemoperfusion in the case of first-order adsorption and desorption, with first order corporeal elimination. The results indicate that one of the resins used, Amberlite XAD4, already known as a haemocompatible resin, is useful in eliminating theophylline. PMID- 4033303 TI - Theoretical study of haemoperfusion: drugs obeying a one-compartment pharmacokinetics model. AB - A general theory of haemoperfusion for drugs obeying the one-compartment pharmacokinetics model is proposed. The following theoretical cases are investigated: First case Adsorption and desorption are first-order reactions without biotransformation, and elimination rate is first-order. Two particular cases are examined: no desorption and alpha = beta. Second case: Adsorption and desorption rates are first-order, without biotransformation, and elimination rate is zero-order. Third case: Adsorption rate is first-order and desorption rate is zero-order, without biotransformation, and elimination is either first-order or zero-order. Fourth case Adsorption rate is zero-order and desorption rate is first-order, without biotransformation, and elimination is either first-order or zero-order. Fifth case: Adsorption and desorption rates are first-order, with biotransformation. In all these pharmacokinetics models for haemoperfusion, theoretical computations lead to the values of adsorbed amount and plasma level, in relation to time. Clearances are also computed. In most cases, haemoperfusion must be performed quickly because of the desorption phenomenon. Parameters modulating the adsorption process are: surface area, blood flow, drug concentration in blood, adsorbent nature and adsorbent quantity. PMID- 4033304 TI - A method for determining the excretion of volatile substances through skin. AB - A method is described for determining the concentration of volatile substances that are excreted through the skin via insensible perspiration. The technique involves placing the hand into a polyethylene bag maintained at 37 degrees C and allowing the air around the hand to come to equilibrium with the vapors emanating from the skin. Gas samples were removed from the bag and the concentration of volatile substances was determined by gas chromatographic analysis. Using ethanol as a test substance, alcohol excretion from the skin was determined and compared to breath and blood concentration. The results indicate that the concentration of alcohol in insensible perspiration is not substantially different from that of breath or blood following complete absorption. However, during the period of active drug absorption, perspiration alcohol concentration lags behind the blood and breath concentration, and then later has a slightly higher concentration than blood and breath. PMID- 4033305 TI - [Emphysema as a leading symptom]. AB - Air may enter the tissue via injuries of the respiratory and alimentary tracts. The mechanisms governing the entrance of air are traumas, and surgical or anaesthesiological measures; spontaneous entry is also possible. Infections with aerogenic bacteria are very rare. Numerous possible aetiologies for the accumulation of air in the head and neck have been reported. Case reports are given to discuss the pathomechanism and therapy of emphysema as a result of injuries of cranium and larynx, dental treatment, whiplash injury, adenotonsillectomy and spontaneously in asthma. The otolaryngologist should have thorough knowledge of differential diagnosis and prophylactic measures, since therapy depends upon the aetiology. PMID- 4033306 TI - [Myocutaneous island flaps as a new principle in plastic and reconstructive head and neck surgery]. AB - After a brief introductory presentation of typical regional flaps for surgical repair of cervicofacial defects, the author describes the principle, the advantages, and the disadvantages of myocutaneous island flaps. The central position and the great value of the acromiopectoral myocutaneous island flap (pectoralis major-flap) for reconstructive practice are emphasised. This flap allows the total one-stage repair of the hypopharynx and cervical oesophagus. PMID- 4033307 TI - [Septal support made from aluminum oxide ceramics]. AB - Dislocation of the cartilage after surgery on the nasal septum is a common complication. To avoid this complication we developed a so-called septum holder made of biologically inert Al2O3 ceramic for implantation at the anterior nasal spine. PMID- 4033308 TI - [The cervico-cranial syndrome in the practice of the otorhinolaryngologist]. AB - The craniocervical syndrome is an entity whose symptoms: vertigo, cephalea, tinnitus, facial pain, otalgia, dysphagia, pain of the carotid artery are thought to be caused by cervical factors. In the majority of cases the cranio-cervical syndrome is caused by a spondylarthrogenic segmental dysfunction whose pathophysiology is explained. In the pathogenesis lesions of the joints of the skull which may be responsible for pain and dysfunction in the segmental areas are of great importance. The neurology of the joints of the skull, as well as the pathological mechanisms of spondylarthrogenic disturbances, responsible for the different kinds of dysfunction of the equilibrium and for cephalea are discussed. The pathophysiological basis of manual diagnosis is explained; also the radiological findings of the upper cervical vertebral column are principally discussed. A short review of therapeutic recommendations is given. PMID- 4033309 TI - [Importance of the general radiograph of the cervical spine in vertigo and pathologic proprioceptive cervical nystagmus]. AB - The general roentgenogram of the cervical spine often shows manifold pathological alterations by patients without any clinical complaints. On the other hand, there are cervical vertigo and different symptoms caused by the cervical spine, its joints, muscles and ligaments without any X-ray manifestation. Nevertheless, some connections are assumed to exist between vertigo and alterations of the cervical spine an assumption supported especially by the frequently successful elimination of cervical troubles by chirotherapy. We compared the X-ray manifestations in patients complaining of vertigo with any and without any pathological proprioceptive cervical nystagmus provoked by examination according to Moser and revealed by electronystagmography. The extended posture of the cervical spine seems to point to a possible cause of vertigo. Likewise, some degenerative alterations seem to exercise a pathological effect, provoking cervical vertigo additionally if both effects are combined. Uncovertebral arthroses seem to have the same effect without occurring in combination with other effects. The general roentgenogram of the cervical spine in the sloping, lateral and anterior posterior direction may consequently point to some possible causes of cervical vertigo. PMID- 4033310 TI - [Evidence for the validity of an extended theory of Barany]. AB - The results published in literature of caloric tests in face-up position are compared to these obtained in face-down position. The rates of convective flow and expansion of the endolymph are evaluated. The theory of Barany continues to be valid, because the rate of convection is greater than that of expansion. Together with the expansion effect the theory explains caloric nystagmus under terrestrial conditions and under conditions in space, i.e. in the absence of gravitation. PMID- 4033311 TI - [So-called laryngeal nystagmus. Progressive myoclonus as a symptom of a cerebellar and brain stem infarct]. AB - The present article describes a patient with ischemia in the vascular territory of the posterior inferior cerebellar artery, who developed in addition to other typical signs of the dorsolateral medulla oblongata, myoclonic movements of the ipsilateral vocal cord. Within a period of one year, the myoclonic movement progressed, leading to bilateral involvement of the velo-pharyngeal muscles. The essential neuropathological lesion is considered to be an impairment of the dentato-olivary System. In this respect there is a close relationship to other types of rhythmical myoclonus due to lesions of the brain-stem and cerebellum. PMID- 4033312 TI - [A smelling prosthesis for laryngectomized patients]. AB - An instrument is presented which helps the laryngectomee to smell. It consists of a tube placed between tracheostoma, mouth and nose. The laryngectomized person is able to ventilate his nose with the help of this aid. Moreover, it also aids in blowing the nose and inhaling in case of nasal catarrh. PMID- 4033313 TI - [Clinical aspects and therapy of esophageal candidiasis]. AB - In 14 patients with candida infection of the oesophagus, the clinical, radiologic and endoscopic findings are described. It is pointed out that candida mycosis of the oesophagus may occur primarily and without underlying disease. The authors report on the therapy of candidiasis. PMID- 4033314 TI - [Antibiotic therapy in patients with renal insufficiency]. AB - For the otolaryngologist (ENT specialist), too, antibiotics are among the most frequently prescribed drugs. This article gives the essential fundamentals for the antibiotic treatment of patients with restricted kidney functions, as well as advice for antibiotic therapy in clinics and in medical practice. PMID- 4033315 TI - [The use of antibiotics and chemotherapeutic agents during pregnancy]. AB - Physicians engaged in all general and specialist fields of medicine may at times be confronted with the necessity of prescribing an antibiotic or chemotherapy for pregnant patients. This article gives ample advice on the therapy with antibiotics and chemotherapeutic agents during pregnancy. PMID- 4033316 TI - [The execution of the modified Thornell operation]. PMID- 4033317 TI - [Submucous turbinate resection]. AB - This article describes the authors' experiences on submucous resection of the turbinate bone in chronic hypertrophic lower turbinates. Similar to the procedure in septoplasties, this surgery preserves the mucosa and its physiological properties. The technique is facilitated by an amazingly low tendency to bleeding. 70 patients were followed up post-operatively. More than 70% reported a marked improvement of nasal breathing. No serious complications were seen. PMID- 4033318 TI - [Dysontogenetic median maxillary cysts]. AB - Nasopalatine duct cysts, median palatine cysts and nasoalveolar cysts belong to the developmental cysts of the upper jaw. They are situated at the midline in the fusion areas of embryonic facial processes and for this reason are known as "fissural cysts". They are, therefore, not of odontogenic origin and, on account of their relationship to the mouth, the nose and the nasal cavities, are of practical relevance to the otolaryngologist. The various clinical symptoms and the histological findings are described, and a review of the literature is presented. PMID- 4033319 TI - [Computer or conventional tomography? Comparative studies in craniofacial fractures]. AB - Both conventional tomography and computed tomography are usefully employed in examinations of facial and frontal skull base fractures. Whereas computed tomography offers an excellent high-resolution image, conventional tomography yields a better spatial representation. The advantages and limitations of these techniques in the diagnosis of facial and frontal skull base fractures are presented and discussed. PMID- 4033320 TI - [Metastasizing mucoepidermoid carcinoma of the parotid gland. Case report]. AB - This article reports on a high-grade mucoepidermoid tumour with a wide lymphogen and haematogen spread. The patient's further malignomas, a carcinoma of the great bowel and the urinary bladder, remained without metastases. PMID- 4033321 TI - [Angiolymphoid hyperplasia with eosinophilia (Kimura disease)]. AB - A case of a rare disease, known as angiolymphoid hyperplasia with eosinophilia, or Kimura's disease, is described in order to discuss the histopathology, aetiology and differential diagnosis by means of literature. The clinical symptomatology consisting of the appearance of cutaneous or subcutaneous tumours is reported as well as the histological features. The therapy of choice is the surgical treatment of the tumour, whereas in most cases radiation or large-dosed therapy with corticosteroids leads to remissions only. PMID- 4033322 TI - [Treatment of tinnitus with iontophoresis and local anesthesia]. AB - 50 previously unsuccessfully treated patients suffering from tinnitus were given local-anaesthesia-iontophoresis. By iontophoresis it is possible to build up an electric field, in which a local anaesthetic (lidocaine hydrochloride) is able to penetrate through the tympanic membrane. Experimentally it has been proven that this local anaesthetic has a direct effect on the inner ear. In contrast to intravenous and intratympanal application there are no toxic side effects when applying local-anaesthesia-iontophoresis. Tinnitus was reduced completely or partly in 31 patients after repeated application to one or both ears. No connection was seen between the success of therapy and the origin of the tinnitus. Treatment was unsuccessful in 19 cases. No serious side effects were seen. Local-anaesthesia-iontophoresis can be recommended as an attempt to treat tinnitus, especially in those cases who have not yet responded to drugs. PMID- 4033323 TI - Fenestration of the horizontal semicircular canal in congenital conductive deafness. AB - Fenestration of the horizontal semicircular canal enables the otologic surgeon to restore hearing in those patients with congenital conductive deafness who are not candidates for stapedectomy, ossicular reconstruction, or tympanoplasty. Since the development of stapedectomy, much of the finesse technique of fenestration surgery has been lost, and many otologic surgeons today are unfamiliar with the fenestration operation. The surgical technique for creating a permanently patent fenestra in the horizontal semicircular canal is described. The causes of failure in fenestration surgery are reviewed. Thirty-three patients who have undergone fenestration for congenital conductive deafness over a 30-year period, and 100 patients who underwent fenestration for otosclerosis in 1950, are reviewed to demonstrate patient selection and the efficacy of this operation in establishing long-term hearing improvement. PMID- 4033324 TI - Open mastoid procedures: contemporary indications and surgical technique. AB - The history of the management of chronic ear disease with and without cholesteatoma is dominated by a canal wall down philosophy. The implication is that such an open procedure insures disease control and an uncomplicated future. In point of fact, problem canal wall down procedures can be fraught with as many serious complications as their more controversial canal wall up counterpart is alleged to propagate. Such problem cavities most commonly result from poor execution of basic technique. The objective of this paper is to identify what constitutes a problem cavity and to describe the authors' techniques to avoid such difficulties. A technique has evolved which not only eradicates disease, but which is self-cleansing and of minimal impact on the patient's lifestyle. The authors' experience with canal wall down procedures is reviewed. PMID- 4033325 TI - Velar closure and ear tubings as a primary procedure in the repair of cleft palates. AB - This ten-year study reviews 36 patients with complete clefts of the hard and soft palates treated with primary velar closure, bilateral myringotomies, and tubings performed when the infant was 12 to 15 months of age. The hard palate and prepalate were not closed until the child was at least 5 1/2 years of age. By early velar closure, a population with an almost 100% incidence of otitis media with effusion has been converted to a population with a 17% incidence of recurrent otitis media requiring repeat myringotomies and tubings. PMID- 4033326 TI - High-grade malignancies of the parotid gland: effective use of planned combined surgery and irradiation. AB - The trend toward treatment of parotid gland malignancies with planned combined surgery and postoperative radiation therapy is currently being followed by many centers, although prospective studies confirming the efficacy of this treatment regimen have only recently begun. We have reviewed only our "high-grade" histologic types: adenocarcinomas, malignant mixed tumors, high-grade mucoepidermoid carcinomas, squamous cell carcinomas, and undifferentiated carcinomas. Acinic cell carcinomas, adenoid cystic carcinomas, and low-grade mucoepidermoid carcinomas were excluded from study because of their different biologic behavior. Since 1974, we have employed the approach of surgical extirpation with preservation of the facial nerve when possible for all parotid tumors, combined with planned postoperative radiation therapy (50-70 Gy). We reviewed the 37 cases of "high-grade" parotid gland malignancies and compared the patients treated with the combined modality approach with our historical patients treated initially with surgery alone. Despite an apparent higher stage at presentation, our combined treatment group ultimately had significantly better local control (70% vs. 20%), and an equivalent survival rate at five years. Tumor was present at the margin of resection in 14 (74%) cases treated with combined surgery and irradiation. The facial nerve was preserved in six of these patients with positive margins, and only one of these patients developed a local or regional treatment failure. In conclusion, our data confirms the efficacy of surgical exploration to determine the extent of disease and surgical resection, preserving facial nerve function if possible, followed by postoperative radiation therapy at adequate doses. Control of local-regional disease was much improved by combined modality therapy as opposed to surgical resection alone, despite the prevalence of residual microscopic disease in the resection margins. Facial nerve function is optimally preserved by this approach of conservative surgery combined with postoperative radiation therapy. PMID- 4033327 TI - Newer technique of tracheoesophageal fistula for vocal rehabilitation after total laryngectomy. AB - In 1982, we published a new technique to create a tracheoesophageal (TE) fistula, using the combination of an endotracheal tube and a flexible fiberoptic nasopharyngolaryngoscope. An even more simple technique using a fenestrated metal Yankauer Tonsillar suction is now introduced. This technique allows for the TE fistula to be made by any level of the tracheo-esophageal junction. It is easily done with topical and local anesthesia with the patient sitting on the otolaryngology examination chair. The method described has been used in 25 consecutive cases with no complications. PMID- 4033328 TI - Pediatric nasal resistance. AB - Rhinometry has provided a quantitative and objective means of assessing nasal airway patency. Previous investigators have established normal nasal resistances for adults and newborn infants. Less material and no such normal references are available for the pediatric ages. In this study, nasal airway resistance is assessed by anterior rhinometric technique in 498 children ranging from four to 16 years of age. Collected nasal resistance data are found to vary inversely with age and fall in an almost linear fashion between already established normals of infancy and adulthood. As far as we can determine, pediatric age specific nasal resistance data with calculated standard deviations and 95% confidence levels have not been previously reported. Such data provides initial age specific reference points enabling the rhinologist to more objectively evaluate concerns regarding nasal obstructive problems in children. PMID- 4033329 TI - Obstructive sleep apnea: variations in surgical management. AB - Forty patients with obstructive sleep apnea (OSA) were either treated by submucous resection, alone or by palatopharyngoplasty (PPP). Before surgery, each patient underwent a thorough sleep evaluation for the diagnosis of OSA. Of the 23 patients treated by submucous resection alone, eight had more than a 50% reduction in their apnea index and were considered successfully treated. Of the remaining 15, ten received a supplemental tongue retaining device (TRD). Five of the ten were markedly improved. The overall success rate in this group was 57%. Of the 17 patients treated by submucous resection and PPP, ten were treated successfully. Six of the remaining seven patients were subsequently treated with a TRD, which was successful in four. The overall success rate in this group was 82%. PMID- 4033330 TI - Autologous fibrin tissue adhesive. AB - Various methods of making fibrin tissue adhesive from a patient's own blood were evaluated. The method using ammonium sulfate for fibrinogen preparation produced the greatest bonding strength. The average bonding strength of the commercially manufactured adhesive and of the autologous fibrin tissue adhesive were compared at 10 minutes and 30 minutes after glueing together 1 X 1 cm samples of fresh human dura. Results indicate the commercial glue holding 57 gms/cm2 at 10 minutes and 123 gms/cm2 at 30 minutes, while autologous glue prepared with the "ammonium sulfate method" has a bonding strength of 41 gms/cm2 at 10 minutes and 217 gms/cm2 at 30 minutes. PMID- 4033331 TI - Lymphoepithelioma (undifferentiated carcinoma) of the laryngohypopharynx. AB - Lymphoepithelioma (World Health Organization type 3, undifferentiated carcinoma of the nasopharyngeal type) is an extremely rare cancer in the laryngohypopharyngeal regions. We found reports of only 6 such tumors in the English language medical literature; 1 of the 6 was from our institution. We report four additional cases seen at the Mayo Clinic. Radiotherapy controlled disease at the primary site in three of the four cases. The neoplasm has a propensity for early, widespread dissemination. Three of our four patients died of extensive visceral and nodal metastases. One patient has survived eight years without a recurrence. PMID- 4033332 TI - Endolymphatic sac surgery for Meniere's disease: a composite study of 339 cases. AB - This paper analyzes 339 consecutively performed endolymphatic mastoid sac shunts. Regardless of the method used, vertigo was controlled and hearing either improved or stabilized in approximately 70% of the cases. Overall, vertigo was controlled in approximately 80% of the cases. Similar results were obtained in cases of Meniere's syndrome and vestibular Meniere's disease. It is suggested here that, regardless of the method employed, there remains a high likelihood that the symptoms will recur, and the question is raised as to whether sac surgery may merely induce a temporary remission of the disease process. Consequently, it is hereby proposed that there is a need to devise a method to permanently drain the endolymph in order to more effectively control the disease on a permanent basis. Until this is achieved, however, sac surgery would appear to be the most appropriate surgical treatment for Meniere's disease. PMID- 4033333 TI - Epidermoid cysts, sulci, and mucosal bridges of the true vocal cord: a report of 157 cases. AB - Presented is a summary of our experience with 157 patients having a diagnosis of epidermoid cyst, glottic sulcus, or mucosal bridge of the true vocal cord. Each patient in this group was diagnosed and treated jointly by a phoniatrist and microlaryngoscopist and then evaluated for results of surgical and phoniatric therapy. Included in the discussion are methods of examination and diagnosis, microanatomy and histopathology of the lesions, methods of treatment, and results of treatment. An argument for a common etiology for these lesions is advanced. PMID- 4033334 TI - Extended follow-up of total inferior turbinate resection for relief of chronic nasal obstruction. AB - Total inferior turbinectomy has been proposed as a treatment for chronic nasal airway obstruction refractory to other, more conservative, methods of treatment. Traditionally, it has been criticized because of its adverse effects on nasophysiology. In this study, patients who had previously undergone total inferior turbinectomy were evaluated with the use of an extensive questionnaire. It confirms that total inferior turbinectomy carries significant morbidity and should be condemned. PMID- 4033335 TI - The bifid uvula: is it a marker for an otitis prone child? AB - All children seen by a pediatrician in a suburban practice during an 18-month interval were examined carefully for the presence of an abnormal uvula. Isolated bifid uvula, without overt cleft palate, was detected among 44 children who had been followed in the practice during the first three years of life. A chart review was performed to determine the frequency of acute otitis media (AOM) and of insertion of tympanostomy tubes among these study patients and among age matched controls with normal uvulas. Compared to control children, a slightly higher proportion of children with bifid uvulas had experienced more than one episode of AOM (64% vs. 49%) and more than three episodes of AOM (16% vs. 8%) during the first year of life, but these differences were not statistically significant. By age 3 years, the incidences of AOM in the compared groups were more nearly equal. Insertion of tympanostomy tubes during the first three years of life for persistent middle ear effusion was slightly more common among the bifid uvula group than among the controls (14% vs. 10%), but this difference again was not statistically significant. Children with bifid uvula may be at slightly increased risk of middle ear problems during the first years of life, but the magnitude of this increase, if any, appears small. PMID- 4033336 TI - Rhinocerebral mucormycosis with internal carotid occlusion: report of two cases and review of the literature. AB - Two fatal cases of rhinocerebral mucormycosis with fungal invasion and occlusion of the internal carotid artery are described. Review of the literature reveals 35 similar cases of whom only 6 survived. Emphasis is placed on the need for early diagnosis and prompt therapy which consists of correction of the underlying disease, aggressive surgical debridement, and amphotericin B. PMID- 4033337 TI - Fourth pharyngeal pouch sinus. AB - This is the first description and documentation of an extremely rare developmental anomaly of the pharyngeal apparatus in a 15-year-old female. The clinical, radiological, histological, and anatomical findings indicated that the anomaly originated in the pharyngeal fourth pouch. It presented as a recurrent lateral neck abscess which was due to a paratracheal sinus. This sinus penetrated the larynx and after a translaryngeal course ended in the pyriform sinus. It was caudad to the superior laryngeal nerve and external to the recurrent laryngeal nerve. Its penetration into the larynx at the cricothyroid joint region could serve as a useful surgical landmark. PMID- 4033338 TI - High frequency needle dissection rhytidectomy. AB - Fifty consecutive rhytidectomies were performed utilizing high frequency needle dissection on one side and standard sharp dissection on the other for all incisions and flap elevation. The efficacy of this technique in hemostasis, prevention of hematoma, and wound healing is compared to the conventional technique of rhytidectomy. The advantages and disadvantages of the modality are discussed. PMID- 4033339 TI - Silastic sheet keel in laryngeal reconstruction. PMID- 4033340 TI - Comminuted fractures of the zygomatic arch: percutaneous circumzygomatic suspension. PMID- 4033341 TI - Flap protection in exostosis surgery. PMID- 4033342 TI - Furosemide ototoxicity: clinical and experimental aspects. AB - Furosemide is an ototoxic diuretic. Furosemide injection is followed by a rapid, but reversible decrease of the endocochlear potential and eighth nerve action potential with a more gradual decrease of the endolymph potassium concentration. In contrast to the reversible effects of furosemide alone on the cochlea, the combination of kanamycin with furosemide resulted in irreversible changes in cochlear function which were associated with elevated levels of kanamycin in the blood and perilymph of the experimental animals. There was a striking similarity between the blood level measured by high pressure liquid chromatography at the time of recovery of auditory function in experimental animals and the ototoxic blood levels proposed by others in clinical literature. These findings help to provide a pharmacologic basis for the clinical observation of furosemide-induced hearing loss. PMID- 4033343 TI - Microvascular anastomosis using the milliwatt CO2 laser. AB - The milliwatt CO2 laser was used to anastomose small vessels in a rat femoral artery model. The technique requires multiple brief applications of 60-70 mW after placement of three equidistant 10-0 nylon stay sutures. The vessel histology is described immediately and 1, 3, 7, and 21 days after the procedure. The laser effects tissue bonding through changes in the collagen of the adventitia and media. Subsequent healing consists of new collagen deposition in the adventitia and reendothelialization of the intima associated with neointimal proliferation at 3 weeks. PMID- 4033344 TI - CO2 laser and suture in splenic parenchyma: an experimental study. AB - Hemisplenectomy was performed with the scalpel in 12 mongrel dogs. The blood vessels of the splenic pedicle were temporarily clamped. In a six-dog group, hemostasis was obtained by CO2 laser and residual bleeding was controlled by sutures. In the other six dogs, group hemostasis was performed only by sutures. The surgical procedure was free of mortality. No hematological changes were observed in both groups. Histological studies revealed a better hemostatic effect and intensive necrosis of the splenic parenchyma in the lasered group compared with the sutured group. PMID- 4033345 TI - Evaluation of the carbon dioxide laser for performance of gastrointestinal myotomies. AB - Using a conventional carbon dioxide laser set at 8-W continuous-wave energy, a technique was developed in the animal laboratory to incise only the muscularis of the pylorus leaving the mucosa and submucosa intact. Similar esophageal myotomies were performed with less success, due to the rich submucosal venous plexus causing obscuring hemorrhage and to the reapproximation of the longitudinal esophageal muscle over a 3-week period. The technique for esophageal myotomy requires further refinement, but pyloromyotomy appears applicable for controlled human trials. PMID- 4033346 TI - Purification of dog VIP from a single animal. AB - VIP, a potent vasodilator peptide, is reported to be identical in pig, cow, human and rat but to differ in four amino acids in chicken. This report describes the purification of dog VIP from the small intestine of a single animal. The purification method is based on tissue extraction with a sequence of organic solvents. The extracted VIP is concentrated onto cation-exchange cellulose and brought to purity by three HPLC steps. A 30% final yield of pure VIP was obtained from the original extract. Dog VIP was found to have the following sequence: His Ser-Asp-Ala-Val-Phe-Thr-Asp-Asn-Tyr-Thr-Arg-Leu-Arg-Lys-Gln-Met-Ala -Val-Lys-Lys Tyr-Leu-Asn-Ser-Ile-Leu-Asn. Thus the amino acid sequence of dog VIP is identical with all the mammalian VIP's which have been reported. This suggests that a high degree of conservation throughout the molecule may be required for VIP bioactivity. PMID- 4033347 TI - Comparison of brown adipose tissue thermogenesis induced by congeners and isomers of phenylpropanolamine. AB - The present experiment compared the effects of intraperitoneal injection (.0223 mMol/kg) of several phenethylamine congeners and isomers including amphetamine (AMP), ephedrine (EPH), methoxyphenamine (MET), norpseudoephedrine (NOR), pseudoephedrine (PS) and phenylpropanolamine (PPA) on in vivo interscapular brown adipose tissue temperature in adult male rats. Comparisons of isomer potency revealed that the 1-isomer was more thermogenic than the d-isomer for EPH and PPA but not for AMP, NOR and PS. Congener potency order was: AMP greater than PPA greater than EPH greater than NOR = MET greater than PS. The implications of these data for the weight-reducing activity of these compounds is discussed. PMID- 4033348 TI - Ethanol increases plasma vasopressin shortly after intraperitoneal injection in rats. AB - In rats, ethanol has generally been thought to inhibit vasopressin (VP) release into the peripheral circulation; however, the primary evidence for this conclusion has been indirect. Radioimmunoassay was used to measure VP in the plasma of rats decapitated 5 or 60 min after intraperitoneal injection of ethanol (2.0 g/kg). Confirming the popular notion that ethanol inhibits VP release, VP levels were decreased 60 min after treatment. But radioimmunoassay techniques also revealed that VP release is markedly stimulated shortly after an injection of ethanol. PMID- 4033349 TI - Plasma dihydroxyphenylglycol (DHPG) in the in vivo assessment of human neuronal norepinephrine metabolism. AB - We investigated the utility of deaminated norepinephrine (NE) metabolites in the study of human sympathetic nervous pathophysiology. Plasma levels of the NE metabolite dihydroxyphenylglycol (DHPG) appear to be related to intraneuronal NE stores. Plasma DHPG increases when sympathetic nervous activity or circulating NE increase and decreases when neuronal NE is depleted or neuronal NE reuptake is blocked. Changes in plasma dihydroxymandelic acid (DOMA) related less closely to changes in plasma NE. The coupling of measurements of plasma NE with its deaminated metabolites and DHPG may improve understanding of human NE metabolism and neuronal NE reuptake. PMID- 4033350 TI - Effects of isomers of apomorphines on dopamine receptors in striatal and limbic tissue of rat brain. AB - The optical isomers of apomorphine (APO) and N-propylnorapomorphine (NPA) were interacted with three biochemical indices of dopamine (DA) receptors in extrapyramidal and limbic preparations of rat brain tissue. There were consistent isomeric preferences for the R(-) configuration of both DA analogs in stimulating adenylate cyclase (D-1 sites) and in competing for high affinity binding of 3H spiroperidol (D-2 sites) and of 3H-ADTN (DA agonist binding sites) in striatal tissue, with lesser isomeric differences in the limbic tissue. The S(+) apomorphines did not inhibit stimulation of adenylate cyclase by DA. The tendency for greater activity or higher apparent affinity of R(-) apomorphines in striatum may reflect the evidently greater abundance of receptor sites in that region. There were only small regional differences in interactions of the apomorphine isomers with all three receptor sites, except for a strong preference of (-)NPA for striatal D-2 sites. These results do not parallel our recent observations indicating potent and selective antidopaminergic actions of S(+) apomorphines in the rat limbic system. They suggest caution in assuming close parallels between current biochemical and functional, especially behavioral, methods of evaluating dopamine receptors of mammalian brain. PMID- 4033351 TI - Changes in LH and prolactin levels in diabetic male rats and the role of the opiate system in the control of their secretion. AB - Diabetic male rat has low serum levels of luteinizing hormone (LH) and testosterone (T), which are accompanied by atrophy of the testes and accessory glands. The present study investigated changes in the serum levels of LH, prolactin (PRL) and glucose, following diabetes induction by streptozotocin. In addition, involvement of the opiate system in the control of LH and PRL secretion was evaluated. There was no difference in PRL levels between diabetic and control animals, except at 8 hours after streptozotocin injection. In contrast, the diabetic animals had consistently lower levels of LH, starting on the second day of diabetes. Blockade of the opiate system by naltrexone caused a sharp increase of LH levels in normoglycemic rats, while only a gradual decrease was observed in hyperglycemic animals. PRL secretion was inhibited by naltrexone, both in diabetic and control groups. It is concluded that, unlike normoglycemic rats, inhibition of LH secretion in diabetes is not under the control of the opiate system, probably as a result of T deficiency. In contrast, PRL secretion in diabetic rats, as in the control group, is under the influence of endogenous opiates. PMID- 4033352 TI - Effect of neonatal thiamine and vitamin A deficiency on rat brain gangliosides. AB - Effects of neonatal thiamine deficiency and vitamin A deficiency on total and fractions of gangliosides (GT1, GD1a, GD1b and GM1) were studied in Charles Foster rat brain at 21 days of age. GT1, GD1b+GD1a and GM1 are being presented here as poly-, di- and mono-sialo gangliosides. Thiamine and vitamin A deficiencies were induced by feeding mothers essentially thiamine and vitamin A free diets respectively. A normal control (G+L+) and weight matched undernourished groups (G+L- for thiamine and LL for vitamin A experiments) were used for comparison. At 21 days, the concentration of total gangliosides in thiamine deficient and G+L- rat brains were 49.0% and 45.7%; in vitamin A deficient and LL group were 66.6% and 88.0% of the G+L+ group, respectively. The percent contribution of poly-, di- and mono-sialo gangliosides in G+L+/thiamine deficient/G+L- were; 17.2/46.8/73.5, 54.4/51.7/14.2, and 6.6/8.7/5.8, respectively. The percent contribution of poly-, di- and mono-sialo gangliosides in G+L+/vitamin A deficient/LL were; 19.3/39.9/43.7, 57.0/37.6/35.1, and 8.4/11.6/19.7 respectively. The changes observed in these experiments suggest an underlying possibility of metabolic defect in undernourished animals. PMID- 4033353 TI - Tolerance to morphine-induced analgesia in mice: magnetic fields function as environmental specific cues and reduce tolerance development. AB - Mice receiving daily injection of morphine (10 mg/kg) developed tolerance to morphine-induced analgesia, such that after 5-7 days of treatment their thermal response (paw licking) latencies in the hot plate test were indistinguishable from those of control animals. Exposure to a rotating magnetic field for thirty minutes before the daily morphine administrations significantly reduced the development of tolerance. These magnetic exposures also significantly increased over 7-10 days the basal nociceptive thresholds and paw licking response latencies of saline treated mice. Control and sham exposed mice that were fully tolerant to the analgesic effects of morphine failed to show any tolerance to morphine-induced analgesia when exposed to the magnetic stimuli prior to injection. Likewise, the partial tolerance to morphine shown by mice exposed to the rotating magnetic field pre-injection environmental cues was eliminated when control or sham pre-injection cues lacking the magnetic stimuli were provided. In all cases tolerance to morphine-induced analgesia was evident in the subsequent re-test with the original cues. These results indicate that magnetic field exposure can reduce the development of tolerance to the analgesic effects of morphine. They also show that magnetic stimuli function as significant environmental cues for the development of tolerance to morphine-induced analgesia. This suggests that magnetic stimuli affect both the associative (classical conditioning) and non-associative (physiological, pharmacological) mechanisms involved in the development of opiate tolerance. PMID- 4033354 TI - Ethanol, the choline requirement, methylation and liver injury. AB - The findings obtained in this laboratory and others over the past decade are discussed in order to formulate a thesis, indicating the adverse action of ethanol on a vital methylation process in the liver. Evidence is shown that the rat may have a means of compensating for this impairment in methylation whereas humans do not have this same ability to protect against this action of ethanol. These considerations may offer a basis of why rats are apparently more resistant to alcoholic liver injury than humans. PMID- 4033355 TI - Relationship between reversible acetylcholinesterase inhibition and efficacy against soman lethality. AB - Carbamate pretreatment (45% inhibition, reversible), combined with therapy, protected rats from soman-induced lethality [The Pharmacologist 23, 224 (1981)]. The present study was done to see if less than 45% inhibition protects and to see if reversible acetylcholinesterase (AChE) inhibition and efficacy against soman lethality are correlated. At 30 min pre-soman, guinea pigs and rats received (im) either pyridostigmine (Py) or physostigmine (Ph) to inhibit whole blood AChE from 10 to 70%; at 1 min post-soman (sc), they received (im) atropine (16 mg/kg)/2 PAMCl (50 mg/kg) and mecamylamine (0.8 mg/kg)/atropine (16 mg/kg), respectively. Protective ratios (PRs) were computed and they ranged from 3.1 to 7.7 for guinea pigs and from 1.8 to 2.4 for rats. In guinea pigs the PRs for Py + therapy were roughly similar to those of Ph + therapy. In both species at 30 min after im injection of Py and Ph, a linear relationship was found between percentage of whole blood AChE inhibition and ln dosage of carbamate. Positive correlation (p less than 0.05) was found between the degree of reversible AChE inhibition by pretreatment, coupled with therapy, and efficacy against soman lethality. The present data indicate that inhibition levels as low as 10% may provide some protection. PMID- 4033356 TI - Effects of tranylcypromine treatment on neuroendocrine, behavioral, and autonomic responses to tryptophan in depressed patients. AB - Effects of intravenous administration of the serotonin precursor tryptophan (TRP) on serum prolactin, neuromotor function, subjective mood, and blood pressure and pulse were determined in nine depressed patients before and during placebo controlled treatment with the monoamine oxidase inhibitor (MAOI) tranylcypromine. Tranylcypromine significantly increased the prolactin response to TRP. Four patients developed a distinctive neuromotor syndrome following TRP during tranylcypromine, but not placebo, treatment. Symptoms included hyperreflexia, ankle clonus, nystagmus, incoordination, tremor, myoclonic jerks, and nausea. There were no differences in peak prolactin, mood, or autonomic responses between patients with and without the syndrome, but those with the syndrome had received active tranylcypromine for a significantly shorter duration. Tranylcypromine had little effect on TRP-induced changes in mood or autonomic function, except for a modest enhancement of the TRP-induced rise in diastolic blood pressure. These results suggest that tranylcypromine treatment may enhance serotonin function in depression. PMID- 4033357 TI - Narcotic antagonist-induced hypotension in the spontaneously hypertensive rat. AB - Intravenous naloxone or naltrexone produced transient, dose-related reductions in the mean arterial pressure (MAP) and heart rate (HR) of urethane-anesthetized spontaneously hypertensive rats (SHRs). Yet these same doses of narcotic antagonists reduced HR but not MAP of normotensive Wistar-Kyoto rats (WKYs). Such effects were not observed upon administration to SHRs of increasing doses of methylnaltrexone, which possesses no central activity. (+)-Naloxone, which does not block opiate receptors, reduced HR but not MAP of both SHRs and WKYs. These findings indicate that SHRs and WKYs differ in their MAP and HR responses to narcotic antagonists. The high doses required for effect plus the brevity of the responses suggest that these drug effects are perhaps not mu-opiate receptor mediated; however, the methylnaltrexone and (+)-naloxone findings clearly implicate a central specificity of action. We conclude that narcotic antagonist induced changes in MAP and HR in SHRs are possibly specific and central in origin yet not mediated by mu-opiate receptors. PMID- 4033358 TI - Rubidium and sodium transport across erythrocyte membrane: alterations due to a circulating factor. AB - Essential hypertension patients can be divided into two groups on the basis of the presence or absence of a plasma factor able to inhibit rubidium uptake and sodium extrusion by the red blood cells. Nearly fifty percent of the patients studied present this factor. Preliminary results show that it is dialyzable, has a molecular weight around 500 daltons and cannot be extracted by chloroform. PMID- 4033359 TI - Differences between the tolerance characteristics of two anticonvulsant benzodiazepines. AB - Clobazam (10 mg/kg) and clonazepam (0.25 mg/kg) were administered to mice twice daily by the intraperitoneal route. The development of tolerance to their anticonvulsant effect was compared using a slow intravenous infusion of pentylenetetrazole as the convulsant stimulus. Tolerance to clonazepam developed gradually throughout a 72 h study and did not become significant until the fifth dose. In contrast, tolerance to clobazam occurred extremely rapidly, after only one dose; it was manifested as a single step and no further significant change in protection was observed. Recovery from benzodiazepine tolerance was also studied and seen to occur rapidly with both these compounds; following cessation of dosing, protection was restored to initial levels within 36-48 h. PMID- 4033360 TI - Decrease in alkaline triglyceride lipase in primary cultured hepatocytes from mice with sarcoma 180. AB - Primary cultured hepatocytes from normal mice and mice with Sarcoma 180 were characterized. The viability of freshly isolated hepatocytes from both sources was over 90% and the cells had a relatively stable population of DNA for a minimum of three days. After incubation with (3H)leucine, the syntheses and secretions of (3H)labeled trichloracetic acid-insoluble materials by hepatocytes from both normal and tumor-bearing mice increased similarly. However, the alkaline triglyceride lipase activity of a homogenate of freshly isolated hepatocytes from tumor-bearing mice was one-third that of cells from normal mice. The activity of hepatocytes from tumor-bearing mice increased less during culture than did the activity of cells isolated from normal mice. PMID- 4033361 TI - Uptake of secondary autoxidation products of linoleic acid by the rat. AB - Incorporation of secondary autoxidation products (SP) of linoleic acid into the rat body was investigated. Radioactive SP was administered orally to a group of 5 rats, and excretions of radioactive substances in feces, urine and respiration were measured and compared with excretions from rats fed linoleic acid and its hydroperoxides. The SP-fed group excreted 45% and the other groups about 10% of the administered radioactivity through feces. Urinary excretion accounted for 52% of activity ingested in the SP group and less than 30% in the other groups. The 14CO2 produced in each group was about 25% of the ingested activity. Incorporation of the radioactive substances of SP into tissues and organs was measured periodically after administration of a single dose. The radioactive substances accumulated in the liver between 12-24 hr after administration and accounted for 2.6% of the total amount given, the highest level of all tissues and organs. This accumulation led to an elevation of serum transaminase activities, an increase in hepatic lipid peroxide, as determined by thiobarbituric acid test, and a slight hypertrophy of liver (1.5-fold). Therefore, absorbed SP appeared to contribute to the deleterious condition of the liver. PMID- 4033362 TI - Effect of KCD-232, a new hypolipidemic agent, on serum lipoprotein changes in hepatoma-bearing rats. AB - Changes in serum lipoprotein profiles were characterized in Donryu rats subcutaneously implanted with an ascites hepatoma line of AH109A cells and the effect of a new hypolipidemic agent with a structure of 4-(4' chlorobenzyloxy)benzyl nicotinate (KCD-232) was estimated. With the growth of hepatoma for periods of up to three weeks, a striking decrease in the high density lipoprotein (HDL) fraction and an enormous increase in the VLDL + LDL (very low density lipoprotein + low density lipoprotein) fraction were found in hepatoma-bearing rats when either precipitation method or electrophoresis was used. These lipoprotein profiles were not influenced by sex. Judging from the electrophoretogram, the increase in VLDL + LDL fraction was due mainly to an increase in VLDL fraction. The oral administration of KCD-232 significantly suppressed the hepatoma-induced increase in VLDL + LDL with little or no influence on the hepatoma-induced decrease in HDL. There existed a positive correlation between the hepatoma weight and (VLDL + LDL)-cholesterol concentration and a negative one between hepatoma and HDL-cholesterol. PMID- 4033363 TI - Effect of brominated vegetable oils on heart lipid metabolism. AB - Normal rats fed for 105 days on an experimental diet made up of standard laboratory chow supplemented with 0.5% of a mixture of brominated sunflower-olive oil (BVO) developed a significant increase in the triacylglycerol content of the heart, liver and soleus muscle compared to controls. In addition, BVO-treated rats had a decrease in plasma levels of triacylglycerol and total and HDL cholesterol. Plasma fatty acid levels and plasma post-heparin lipolytic activities, such as H-TGL, LPL, T-TGL and MGH were similar to those of control animals fed the standard chow alone. Heart PDHa (active portion of pyruvate dehydrogenase) was dramatically decreased in the BVO-fed rats. A faster rate of spontaneous lipolysis was recorded in the isolated perfused preparation of hearts from the experimental animals. The addition of 10(-7) M of glucagon to the perfusate, however, revealed a lipolytic effect comparable to the one observed in the control rats. In summary, our findings of normal fatty acids and low triacylglycerol plasma levels associated with normal activities of the various PHLA (post-heparin lipolytic activity) enzymes suggest that accumulation of triacylglycerol in heart muscle may not be explained essentially in terms of an elevated uptake and/or increased delivery of plasma fatty acids or plasma triacylglycerol. A decreased in situ catabolism of tissue triacylglycerol also appears unlikely because the spontaneous as well as the glucagon induced lipolysis in the heart both were found to be unimpaired.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4033364 TI - Fatty acids of sphingomyelin from amniotic fluid of normal and diabetic pregnancies. AB - Amniotic fluid collected from 14 normal and 11 diabetic patients was analyzed for phospholipids, and separated sphingomyelin and lecithin fractions were further studied for their acid composition by gas liquid chromatography. Notable differences in percent fatty acid composition of sphingomyelin were observed for palmitic (16:0; diabetic less than normal), oleic (18:1; diabetic greater than normal), behenic (22:0; diabetic less than normal) and arachidic acid (20:0; absent in diabetics) in the specimens studied. Notable differences were not observed in fatty acids from lecithin fraction. Fatty acid composition of sphingomyelin from amniotic fluid is similar to fatty acid distribution in sphingomyelin from serum and erythrocyte and suggests maternal origin of the lipid. PMID- 4033365 TI - The di- and triesters of the lipids of steer and human meibomian glands. AB - Three groups of diesters have been isolated and identified in the lipids of steer meibomian glands. The first group, designated as alpha Type I, with the abbreviated formula FA-alpha OHFA-FAlc, consisted of alpha-hydroxy fatty acids esterified to fatty acids and fatty alcohols in the approximate molar ratio 1:1:1. The second group, designated as omega Type I-St, with the abbreviated formula FA-omega OHFA-St, consisted of omega-hydroxy fatty acids esterified to fatty acids and sterols in the approximate molar ratio 1:1:1. The third group, designated as alpha, omega Type II, with the abbreviated formula FA-alpha, omega diol-FA, consisted of alpha, omega-diols esterified to 2 moles of fatty acids. The sum of the different diesters comprised about 9% of total steer meibomian lipids. Capillary GLC of the fatty acids of alpha Type I diesters showed the fatty acids to be a family with a two-cluster profile, one at C12 to C20 and the other at C21 to C31, with anteiso chains predominating. Fatty acids from omega Type I-St and alpha, omega Type II diesters gave mainly a one-cluster profile in the short chain region with prominent anteiso and C18:1 peaks. Fatty alcohols of alpha Type I diesters were mainly long chain, C23 to C30, with anteiso chains predominating, while the alpha-hydroxy fatty acids were short chain C13 to C18 acids with C16 predominating. The sterols in diesters omega Type I-St were cholesterol (approximately 60%), delta 7 cholestenol (approximately 35%) and an unidentified compound (approximately 5%) with a GLC retention time slightly longer than delta 7 cholestenol on SE-30 phase. The omega-hydroxy fatty acids and alpha, omega-diols both were of exceedingly long chain lengths, C29-C38, and showed similar GLC profiles. Two types of triesters comprising approximately 1% of total steer meibomian lipids have been isolated but incompletely characterized. In terms of molar ratios, one group of triesters gave fatty acids:omega-hydroxy fatty acids:alpha-hydroxy fatty acids:sterols + fatty alcohols as approximately 1:1:1:1. The other contained fatty acids, alpha-hydroxy fatty acids and alpha, omega-diols in what appears to be a complex mixture of several triesters. Diesters omega Type I and alpha, omega Type II also were found in human meibum. Hitherto these two diesters have not been found in any animal tissue. PMID- 4033366 TI - Biosynthesis of lipids by bovine meibomian glands. AB - Isolated bovine meibomian glands incorporated exogenous [1-14C]acetate into lipids. Thin layer chromatographic analysis of the lipids showed that wax esters and sterol esters contained 61% of the total label. Radio gas liquid chromatographic analysis of the acid and alcohol moieties of both ester fractions showed the label was distributed equally between the two portions of the ester in both cases. Cholesterol and 5-alpha-cholest-7-en-3 beta-ol were the major labeled sterols, and anteiso-C25, anteiso-C27 and anteiso-C23 were the most highly labeled alcohols. The major labeled fatty acids in the wax esters were anteiso C15, n-C16, anteiso-C17 and n-C18:1, whereas anteiso-C25 and anteiso-C27 were the major labeled acids in the sterol esters. The diester region with 6% of the total label contained labeled fatty acids and fatty alcohols each with anteiso-C25 as the major component and omega-hydroxy acids in which n-C32:1 was the major labeled component. The triglyceride fraction which contained 8% of the total lipids was composed of labeled fatty acids similar to those found in both sterol and wax ester fractions. Chromatographic analyses of the labeled lipids derived from exogenous labeled isoleucine showed that anteiso-branched products were preferentially labeled. The labeled triglyceride fraction derived from [U-14C] isoleucine also contained esterified C15, C13, C11, C9, C7 and possibly shorter anteiso-branched acids. PMID- 4033367 TI - Red blood cell tocopherol and liver tocopherol in hyperlipemic rats as compared with plasma tocopherol. AB - In rats with hyperlipemia induced by Triton WR-1339, changes in tocopherol concentrations in plasma and RBC were compared with those in the liver and its subcellular fractions, microsomes and mitochondria. After daily injection with Triton, plasma total lipids at 3 days and 7 days, respectively, showed elevations 6.5 times and 15 times as high as those in the control rats, and triglycerides showed the most predominant elevation. With the hyperlipemia, the concentrations of tocopherol in RBC and the subcellular fractions decreased, as plasma lipids and plasma tocopherol increased, while no change occurred in tocopherol concentrations in liver homogenates. The changes in the ratio of tocopherol to total lipids in plasma coincided with changes in tocopherol concentrations in the RBC and subcellular fractions. PMID- 4033369 TI - Symposium. Papers from the symposium on Analyses by Iatroscan TLC/FID System presented at the 75th AOCS annual meeting in Dallas, Texas, April 1984. PMID- 4033368 TI - Decreased phosphatidylcholine in the lung fluid of patients with sarcoidosis. AB - Surfactant decreases the immune response of lymphocytes. Pulmonary sarcoidosis is a disease characterized by an increased number and activity of lymphocytes in the lung. We measured the lipids and lymphocytes retrieved from the lung by bronchoalveolar lavage. Thirteen patients with active pulmonary sarcoidosis had a significantly higher percentage of lymphocytes (18 +/- 21%, mean +/- standard error of the mean) than 10 control subjects (4 +/- 1.9%, p less than 0.01). Using an external marker, we found the absolute amount of disaturated phosphatidylcholine to be higher in the control group (174 +/- 17.4 micrograms/ml lung fluid) than in the sarcoid group (91 +/- 1.9 micrograms/ml of lung fluid, p less than 0.002). PMID- 4033370 TI - Determination of the phospholipid composition of trout gill by Iatroscan TLC/FID: effect of thermal acclimation. AB - The phospholipid composition of gill tissue from thermally acclimated rainbow trout, Salmo gairdneri, was determined by Iatroscan analysis following an initial development of the chromarods in a non-polar solvent to remove neutral lipids. Standard curves for all phospholipids, although linear through most of the concentration range tested (1-40 micrograms), extrapolated to negative intercepts on the ordinate, indicating a decline in sensitivity at low phospholipid levels. In addition, the concentration dependence of the Iatroscan response varied by nearly 6-fold among phospholipids. Of the major phospholipids, only lysophosphatidylcholine could not be quantitated accurately because of the presence of an interfering peak. Quantitation by Iatroscan yielded results which, in general, agreed well (within 5%) with results obtained by an independent phosphate analysis. Only in the case of phosphatidylinositol (PI) did the two analytical methods differ significantly; proportions of PI were 55% higher when determined by Iatroscan as opposed to phosphate analysis. Gill tissue from 5 C acclimated trout possessed higher proportions of phosphatidylethanolamine than tissue from 20 C-acclimated trout. The Iatroscan provided a rapid and reliable means of quantitating the proportions of all the major phospholipids of trout gill, although there are some limitations to the general applicability of the technique. PMID- 4033372 TI - Quantitating heart lipids: comparison of results obtained using the Iatroscan method with those from phosphorus and gas chromatographic techniques. AB - The precision and accuracy of the Iatroscan method was evaluated by comparing the results obtained with established phosphorus and gas chromatographic techniques. A complete lipid class analysis of rat heart lipids was chosen in order to evaluate the performance of the Iatroscan method for biological samples which contained both neutral lipids and phospholipids. A partial scan and repeat development with chloroform/methanol/water (68.5:29:2.5) was introduced to achieve consistently good separations of the phospholipids on the Chromarods in the Iatroscan method. The results showed that the precision of the Iatroscan method for some lipid classes was comparable to that of phosphorus or gas chromatographic techniques, while for other lipid classes it was lower. Compared to the data obtained using the phosphorus method, the Iatroscan data were generally similar, while the gas chromatographic method generally gave lower values. These findings, together with the advantages of time required for analysis, size of sample, and universality of detection, suggest that the Iatroscan is a valuable complementary method for complex lipid analyses. PMID- 4033371 TI - Comparison of the thin layer chromatography/flame ionization detection system with other methods for the quantitative analysis of liver lipid contents in alcohol-fed rats and controls. AB - In this study, we have examined the feasibility of using the Thin Layer Chromatography/Flame Ionization Detection (TLC/FID) system to evaluate the lipid content of alcohol-induced fatty liver by comparing the results with those from other methods. Various amounts of standards (tripalmitin, phosphatidylcholine and cholesterol) were spotted on Chromarods and scanned either with or without development in a solvent system. The detector responses were significantly greater when the spots were not developed. From the results with developed rods, conversion factors (amount/area) were calculated. These were used for the quantitative analysis of the liver lipids from rats fed a Lieber-DeCarli ethanol diet or a control diet for four weeks. The triglyceride (TG), phospholipid (PL), cholesterol (CH) and cholesterol ester (CE) contents (65.9, 25.4, 2.9 and 6.8 mg/g, respectively) obtained by the TLC/FID system were similar to those observed by other methods (67.9, 27.6, 3.0 and 8.3 mg/g, respectively). The liver lipid content in control rats also was similar to that obtained by other methods (TG, 19.0 vs 20.6; PL, 24.2 vs 21.8, CH, 2.1 vs 2.1 and CE, 1.8 vs 2.6 mg/g). Thus, the magnitude of changes in liver lipid levels due to chronic alcohol ingestion obtained by alternate methods also was found with TLC/FID. The TLC/FID system provides a convenient method for rapid analysis of the extent of fatty liver in alcohol-fed animals. PMID- 4033374 TI - Calculated T1 images derived from a partial saturation-inversion recovery pulse sequence with adiabatic fast passage. AB - Calculated T1 images of the head and abdomen have been obtained using an alternating partial saturation-inversion recovery pulse sequence. Timing parameters were adjusted to yield optimum T1 contrast-to-noise ratio for this sequence for the range of T1 studied. Adiabatic fast passage (AFP) was implemented for the nonselective inverting pulse, to reduce the sensitivity of the measurement to RF and static field inhomogeneity. A nonlinear frequency sweep was used to improve the efficiency of the AFP pulse. The effect on the T1 calculation of slice selection during the pi/2 pulses was also determined and corrected for in the image reconstruction algorithm. The T1's determined by this method show a standard deviation of less than 10%, and good agreement with the literature. PMID- 4033373 TI - The use of the Iatroscan TH-10 analyzer to quantify total lipids in a variety of sample types and lipid classes in human gallbladder bile. AB - Two methods for the measurement of total lipid weight in biological and geological samples and the major lipid classes in human gallbladder bile using the Iatroscan TH-10 analyzer are described. Total lipid determination involves the application of small (5 microliter) volumes to Chromarods, focusing of the sample into one band by partial development in chloroform-methanol (1:1), and quantification by flame ionization detection (FID). The response variation between different sample types did not affect the linearity of response, allowing a reproducibility of +/- 10% of the mean or better for samples ranging from 0.5 to 32 micrograms. Total lipid determinations in 10 samples could be performed in 30 min. The three major components of human gallbladder bile (cholesterol, phospholipids and bile acids) also were quantified with the Iatroscan. Samples focused on Chromarods were separated using a double development scheme in two solvent systems. All three components exhibited a linear response over the range of 0.25 to 8 micrograms. The repeated scanning of rods required at concentrations greater than 3 micrograms did not affect linearity of response. Samples from 10 patients could be processed in less than one hr. Several techniques are discussed to increase reproducibility when performing quantitative lipid analysis with the Iatroscan. PMID- 4033375 TI - Observations of energy metabolism in neuroectodermal tumors using in vivo 31P NMR. AB - The energy metabolism of living tumors in rats and hamsters were investigated by obtaining in vivo 31P-NMR spectra, and the effects of chemotherapy on tumors were evaluated by observing the changes of these spectra. Tumor cells of rat glioma, human glioblastoma and human neuroblastoma were inoculated subcutaneously in the lumbar region of the animals. After the tumor grew to over 1.5 cm in diameter, in vivo 31P-NMR spectrum data was obtained selectively from the tumor with a TMR-32 spectrometer (Oxford Research Systems, U.K.). Several peaks (ATP, inorganic phosphate (Pi), phosphodiesters and phosphomonoesters (PME) were observed in the tumors. The heights of these peaks varied widely corresponding to the tumor growth. However, the spectrum pattern of each tumor in an active stage was found to be essentially the same regardless of histological type or tumor origin. The phosphocreatine (PCr) peak was small, ATP and PME peaks were large and tissue pH calculated from the chemical shift of Pi was low in each tumor group. After intravenous injection of a large dose of a chemotherapeutic agent, ATP peaks decreased and the Pi peak increased gradually, resulting in a dominant Pi peak pattern after several hours in all groups. With lower drug doses, spectrum changes were temporarily seen in the tumors. These findings indicated that drugs with a high dose have a selective and a direct action on the energy metabolism of tumor tissues. In vivo 31P-NMR spectra measurement is very valuable not only to investigate the energy metabolism in tumor tissue but also to evaluate the effects of chemotherapy on the tumor. PMID- 4033376 TI - A study of the freezing of water in human uterine muscle by proton magnetic resonance. AB - Human uterine muscle and its nuclear fractions have been studied by means of nuclear magnetic resonance at temperatures from 300 degrees K to 143 degrees K. Different proton populations have been detected above and below the freezing point. On this basis it is suggested that the freezing of water in uterine muscle starts at the cell nuclei. PMID- 4033377 TI - Improvements in the clinical utility of calculated T2 images of the human brain. AB - Magnetic Resonance Imaging (MRI) affords a considerable improvement in image contrast over other methods by virtue of the intrinsic NMR parameters spin density, T1, and T2. However, the clinical utility of routine quantification of these parameters is currently unknown. Calculated T2 images might afford additional disease specific information provided the calculation algorithm generates accurate T2 values. In this study, calculated T2 images of a MnCl2 phantom (spanning a T2 range of interest of 45.7 ms to 346.6 ms at 6 MHz) were generated utilizing a variety of calculation algorithms based upon a data set of 32 sequential spin-echo (SE) images. In general, when utilizing only the earliest sequential SE after the 90 degree pulse for the T2 calculation, the greater the number of SE used in the calculation algorithm, regardless of how they were averaged, the more accurate and less noisy was the calculated image. When only limited numbers of SE were used in the calculation algorithm, accuracy and noise varied with the choice of TE suggesting that there may be optimal timings for TE for a particular T2 range of interest. Forty-two calculated T2 head images of normal subjects, based upon data sets of 16 sequential SE, were evaluated for the T2 values of normal brain. These were compared to T2 images calculated via 7 different algorithms based upon 16 SE data sets from two patients with CNS pathology. An optimal algorithm was identified in which 16 SE Carr-Purcell Meiboom-Gill (CPMG) were averaged into two images for the T2 calculation. With this algorithm, calculated images could be generated efficiently which were accurate and relatively noise free. The availability of such images maximized whatever disease specificity, and thus clinical utility, T2 information affords. PMID- 4033378 TI - Magnetic resonance of brain tumors: considerations of imaging contrast on the basis of relaxation measurements. AB - Proton spin-lattice and spin-spin relaxation times have been measured in surgically-removed normal CNS tissues and a variety of tumors of the brain. All measurements were made at 20 MHz and 37 degrees C. Between grey and white matter from autopsy human or canine specimens significant differences in T1 or T2 were observed, with greater differences seen in T1. Such discrimination was reduced in samples obtained from live brain-tumor patients due to lengthening in T1 and T2 of white matter near tumorous lesions. Edematous white matter showed T1 and T2 values higher than those of autopsy disease-free white matter. Compared to normal CNS tissues, most brain tumors examined in this study demonstrated elevated T1 and T2 values. Exceptions, however, did exist. No definitive correlation was indicated on a T1 or T2 basis which allowed a distinction to be made between benign and malignant states. Furthermore, considerable variation in relaxation times occurred from tumor to tumor of the same type, suggesting that within a tumor type there are important differences in physiology, biology, and/or pathologic state. Such variation caused partial overlap in relaxation times among certain tumor types and hence may limit the capability of magnetic resonance imaging (MR) alone for the diagnosis of specific disease. Nonetheless, this study predicts that on the basis of T1 or T2 differences most brain tumors are readily detectable by MR via saturation recovery or inversion recovery with appropriate selections of pulse-spacing parameters. In general, tumors can be discriminated against white matter better than grey matter and contrast between glioma and grey matter is usually superior to that between meningioma and grey matter. This work did not consider tissue-associated proton density which should be addressed together with T1 and T2 for a complete treatment of MR contrast. PMID- 4033379 TI - Nuclear magnetic resonance imaging of pulmonary infarction and oedema in excised cadaver lungs. PMID- 4033380 TI - A method for imaging of chemical shift or magnetic field distributions. AB - A phase encoding method for imaging of chemical shift or magnetic field distributions is described. The method utilizes the spin-echo principle and the time period between signal collection and excitation is constant but the time period between excitation and the 180 degrees pulse is varied by constant steps. The method is relatively easy to apply with the Fourier or projection reconstruction methods. PMID- 4033381 TI - Abstracts of papers presented at the third annual meeting, Society for Magnetic Resonance Imaging. March 22-26, 1985, San Diego, California. PMID- 4033382 TI - [Teleradiotherapy of laryngeal cancer using a gas hypoxic mixture (GHM-10)]. AB - A total of 96 laryngeal cancer patients were studied. A comparative analysis of short-term therapeutic results was performed in 2 similar groups: patients receiving radiotherapy without GHM-10 (50) and those receiving radiotherapy with the use of GHM-10 containing 10% of oxygen and 90% of nitrogen (46). Irradiation methods and general tactics of the patients management in both groups were identical. No differences in the short-term results were noted. Radiation reactions of the healthy tissues were less pronounced and noted less frequently in the patients on radiotherapy with the use of GHM-10. PMID- 4033383 TI - [Radiation and chemoradiation therapy of malignant laryngopharyngeal tumors]. AB - The paper is concerned with the results of open field gamma-beam therapy using grid filters. A group of patients with Stage III-IV tumors received chemoradiotherapy. A single focal radiotherapeutic dose varied from 1.6 to 2.5 Gy, a summary dose from 55 to 70 Gy depending on tumor stage and histological structure. A chemotherapeutic drug was prescribed within the limits of 1/2-2/3 of a standard dose. Intensive substitution and blood-stimulating therapy was provided. With the use of different radiotherapeutic and chemoradiotherapeutic methods the 3- and 5-year survival rates were 19.8% and 14.3%, respectively. PMID- 4033384 TI - [Radiation therapy with local UHF hyperthermia in the late stages of laryngeal cancer]. AB - Altogether 47 patients with advanced laryngeal and laryngopharyngeal tumors were treated. Twenty-six patients received multimodality therapy including local UHF hyperthermia and gamma-beam therapy; 21 patients receiving radiotherapy only were entered in the control group. Hyperthermia was induced by the electromagnetic field with the frequency of 2450 and 915 MHz. Parus and Plot units were used. External irradiation was provided. Clinically, complete primary tumor regression was achieved in 20 of 26 patients. A positive effect was absent in 3 cases when metastasis size was 10 X 12 X 8 cm. In the control group, clinically complete tumor regression was noted in 2 patients only. In 4 cases the effect was insignificant, in the rest of 15 cases various degrees of a decrease in tumor and metastasis sizes were revealed. PMID- 4033386 TI - [Use of nicotinic acid and midocalm for correcting blood coagulation in patients with radiation edema of the extremities]. AB - A study was made of the functional activity of platelets, plasmatic coagulation and fibrinolysis in patients with late radiation disorders of the blood and lymph flow during treatment with vasodilative drugs: nicotinic acid and midocalm. These drugs tend to decrease the functional activity of platelets and to raise the blood fibrinolytic activity. Their use is indicated to this group of patients to better their intravascular status. PMID- 4033385 TI - [Effectiveness of the radiation therapy of lung cancer with conventional and median dosage fractionation]. AB - A total of 202 patients were studied: 100 patients received radiotherapy of a primary tumor under conditions of mean fractionation and 102 under conditions of common fractionation. In common fractionation a single focal dose was 2 Gy, 5 times a week, a summary dose 50-60 Gy. In mean fractionation a single focal dose was 3 Gy, 3 times a week for 6 week up to a sum of 54 Gy which was equivalent to 60 Gy in common fractionation. In mean fraction 58 patients received radiotherapy only, 42 radiotherapy with adjuvant chemotherapy. In common fractionation the patients' 1,3 and 5-year survival rates for the control group were 52.8, 14.4 and 10.2% respectively. Under conditions of mean fractionation the 3-year survival rate was 14.2%, i. e. similar to that in the control group. In chemoradiotherapy the 3-year survival rate was 12.4% that might be due to the fact that in spite of Stage III these patients' condition was grave. Pulmonary radiation reaction established by x-ray within 4-6 mos. after the termination of therapy with mean fractionation were marked in 63 of 81 patients, whereas in common fractionation in 30 of 90 patients only. PMID- 4033387 TI - [Contraindications for large-fraction irradiation in malignant glial tumors]. PMID- 4033388 TI - [Basis for the use of enclosed 125I sources for interstitial radiation therapy]. AB - Experimental models of closed sources of 125I low energy photon radiation in the titanium capsules sealed by means of pulsed laser welding were designed. Doses in the tissue equivalent medium from a single 125I point source were calculated using ES-1022 computer, tables for calculating dose fields in different layouts of sources were drawn, and layout parameters in preset doses calculated. Using the 125I source in interstitial irradiation of murine breast tumors one managed to establish the local nature of tissues corresponding to the calculated dose distribution for photon radiation with the energy of 27-35 keV. PMID- 4033389 TI - [Prognosis of the postoperative external respiratory function based on radionuclide research data]. AB - A unified indicator was worked out to have an opportunity before pulmonary operation to predict external respiration function in patients in the postoperative period. The value of partial oxygen pressure in the arterialized blood was proposed as such an indicator. The model made it possible to associate external respiration function with sizes of the involved area and the area of future operation. The main allowance of the model was an assumption of the contribution of any segment to the general process of blood oxygenation. Altogether 11 lung cancer patients were examined. Functional examination of the lungs with 133Xe was performed before a supposed operation. The authors showed a close quantitative and qualitative interrelationship between predicted indicators of partial oxygen pressure in the arterialized blood and corresponding values determined by the methods of blood oxygen measurement in the postoperative period. PMID- 4033390 TI - [Radionuclide study of the joints in rheumatoid arthritis]. PMID- 4033391 TI - [Patient radiation loads during retrograde cholangiopancreatography]. PMID- 4033392 TI - [Optimization of the operating modes for short-focus x-ray therapy]. AB - Basing on experimentally measured energetic radiation spectra of the RUM-7 x-ray unit, absorbed dose distributions in the homogeneous tissue equivalent medium were calculated. An approach to the optimization of the x-ray procedure on the basis of the incident radiation spectrum was proposed. Integral absorbed doses in a pathological focus and in the healthy tissues are used as benefit-damage indicators. PMID- 4033394 TI - [Classification of systems for recording dosage fields]. PMID- 4033393 TI - [Combined (radiation and surgical) treatment of laryngeal cancer patients using metronidazole]. AB - The results of combined treatment of 98 laryngeal cancer patients followed up for 1.5-3 years were analysed. Of them 68 received a preoperative radiotherapy course combined with the electron acceptor compound metronidazole. The drug was given in the form of a sugar syrup suspension at a dose of 100-150 mg/kg bw 2.5-3 hours before each of the 4 fractions of irradiation, at 5 Gy twice a week reaching a summary focal dose of 20 Gy. Thirty patients received radiation therapy without metronidazole. Altogether 4 preoperative radiotherapy methods were used. An analysis of the results showed a significant improvement of the cure rates for laryngeal cancer patients using metronidazole, particularly for those with advanced stages. A better healing of postoperative wounds was noted. The author proved the appropriateness of preoperative irradiation by mean fractions up to a summary focal dose of 20 Gy combined with metronidazole and subsequent (on the last or next day of irradiation) radical operation. PMID- 4033395 TI - [Surgical treatment of a severe postradiation complication]. PMID- 4033396 TI - Cross-sectional thigh components: computerized tomographic assessment. AB - The purpose of this study was to examine the efficacy of the Picker Synerview Fourth Generation CT Scanner in assessing cross-sectional areas of muscle, bone, and subcutaneous fat of the thigh. A secondary purpose was to resolve individual muscle bellies using the CT scanner and to determine the effects of body composition in isolating those muscles. Both limbs of one cadaver were used to compare actual cross-sectional areas with the CT images. Each limb was dissected and photographed. Accuracy of repeated measurements was assessed using human volunteers. Absolute and percent error between the CT measurements and the measurements of the cross-sectional areas differed most at the bone. No differences were found between repeat scans. CT images and photographic measurements of individual muscles were generally quite similar, as assessed by absolute and percent error. The gracilis and sartorious were reasonably well defined in those individuals with more than 8% body fat. The results are discussed in terms of possible applications of the CT scanner in sports medicine research. PMID- 4033397 TI - The instantaneous torque-angular velocity relation in plantar flexion during jumping. AB - Torques, angular velocities, and power of the ankle joint during plantar flexion were measured in jumping experiments in order to achieve insight into shape and magnitude of the instantaneous torque-angular velocity relation in a complex movement. Twelve trained subjects performed maximal vertical jumps from a semi squatting position with 100 degrees of flexion in the knee joint. Ground reaction force measurements and film analyses were used to calculate instantaneous torques, angular velocities, and power outputs during plantar flexion. The shape of the instantaneous torque-angular velocity was different from the well-known hyperbolic force-velocity relation for isolated muscles. Maximal power output (2499 +/- 751 [SD] W) occurred at 60% of the mean maximal torque (301 +/- 62 N X m) and 80% of the mean maximal angular velocity (970 degrees/s). The maximal power output was six times larger than the power output reported in the literature for maximal isokinetic (monoarticular) plantar flexions. Influences like storage of energy in the series elastic component of Hill's muscle model and the role of polyarticular muscles in transporting energy from knee to ankle are discussed. It is concluded that many more selective studies will be necessary before it is possible to relate intrinsic muscle properties to the performance of muscles in poly-articular complex movements. PMID- 4033398 TI - Mechanical and physiological responses to lower extremity loading during running. AB - Fifteen highly trained men performed treadmill running at 12 km X h-1 to determine the effect of lower extremity loading on measures for seven temporal and kinematic descriptors of the running cycle, the mechanical work done on the lower extremity, oxygen consumption (VO2) and heart rate. Five load conditions (no added load and loads of 0.50 kg and 1.00 kg added to either the thighs or feet) were examined. The results demonstrated that VO2 and heart rate increased as load was increased on both the thighs and feet. All changes were statistically significant except for the heart rate changes due to thigh loading. The increases in VO2 due to foot loading--approximately 7.2% per kg of load--were nearly twice as great as those due to thigh loading. The results also demonstrated that 1.00 kg added to the feet produced small but significant increases in stride length (1.4 cm), swing time (9 ms), and flight time (6 ms) and a decrease in peak ankle velocity (0.23 m X s-1). No other load condition resulted in significant changes in any of the temporal and kinematic variables. The results for mechanical work demonstrated that significant increases in the work done on the leg were produced by the loading but that these increases were limited to the loaded segments. Consistent with the data for oxygen consumption and heart rate, mechanical work was increased to a greater extent by foot loading than by thigh loading. It was concluded from these results that the increased physiological demand was directly related to the mechanical work increases, which in turn were attributed to the increased inertia of the loaded segments rather than modifications in the kinematics of the lower extremity movements. PMID- 4033399 TI - Effect of attempted lifting speed on forces and torque exerted on the lumbar spine. AB - Factors affecting compressive and shear forces and torque at the L5/S1 vertebral joint were examined for nine different load/lifting-speed combinations during performances of a dynamic lifting task by 10 subjects. Loads were 40, 60, and 80% of each subject's maximum lifting capability. Target lifting times were 1.5, 3.5, and 7 s. A rigid link model of the human body was used to derive estimates of axial force, shear force, and torque acting at the L5/S1 vertebral joint from high-speed film data. Variables examined empirically were myoelectric activity at the fifth lumbar level of sacrospinalis and intra-abdominal pressure. The respective effects of load and attempted lifting time were assessed through two factor ANOVA's and subsequent Scheffe tests. Heavier loads were found to result in significantly higher (P less than .001) values of mean compressive force, mean shear force, and maximum myoelectric activity. Faster target lifting times resulted in significantly higher mean and maximum values of all the variables quantified except intra-abdominal pressure. PMID- 4033400 TI - Parasympathetic control of resting heart rate: relationship to aerobic power. AB - The degree of parasympathetic control of resting heart rate (PC) was assessed by measurement of variation in heart period (VHP) during cardiopulmonary synchronization of respiration. Respiratory period was arbitrarily preset and standardized at 7 heart beats (3 beats inspiration, 4 beats expiration). The mathematical and experimental evidence for this technique is elucidated. Twenty one healthy subjects were examined for the relationship of aerobic power (VO2max) to (1) VHP and (2) respiratory sinus arrhythmia (RSA) waveform amplitude and phase. Intraindividual variability in VHP was low (test-retest r = 0.97-0.98). VHP in msec was a logarithmic function of VO2max (ml X kg FFW-1 X min-1) according to the equation: 1n VHP = 0.27 + 0.082 X VO2max where r = 0.92, P less than 0.001). VHP was more closely related to VO2max than was resting HR (r = 0.75). In addition, a higher VO2max was associated with a leftward shift of the HR: respiratory cycle sinusoidal curve. These results illustrate the close relationship between aerobic power and vagal tone in control of resting heart rate. Individuals with a higher aerobic power maintain lower resting heart rates mainly via an increase in parasympathetic tone (as opposed to a decreased sympathetic tone). Previous correlations between RSA characteristics and age may be accounted for by age-related decreases in VO2max. PMID- 4033401 TI - Influence of diuretic-induced dehydration on competitive running performance. AB - A diuretic drug (40 mg of furosemide) was utilized to study the effects of dehydration (D) on competitive running performance, without prior thermal or exercise stress. Eight men competed in randomized races of 1,500, 5,000, and 10,000 m, while normally hydrated (H) and with mean plasma volume reductions of 9.9, 12.3, and 9.9%, respectively. As a result of the reduced body water (change in body weight = -1.9, -1.6, and -2.1%), mean outdoor performance times on a running track increased 0.16 min, 1.31 min (P less than 0.05), and 2.62 min (P less than 0.05) in the 1,500-m, 5,000-m, and 10,000-m trials. Running performance decrements due to dehydration were more strongly correlated with changes in body weight (r = -0.79, -0.65, and -0.40) than with urine volume or plasma volume differences. In addition, subjects were studied during submaximal and maximal treadmill exercise while H and D (mean change in plasma volume = -7.1%). Neither submaximal nor maximal oxygen uptake was significantly altered (P greater than 0.05) as a consequence of D. Mean treadmill run time to volitional exhaustion was reduced by 41.4 s (P less than 0.05) during the D treadmill trial. Therefore, it appears that competitive performance in trials of long duration (5,000 and 10,000 m) was affected to a greater extent by D than the shorter 1,500-m event, even though submaximal and maximal oxygen uptake was not altered. PMID- 4033402 TI - Androgens reduce HDL2-cholesterol and increase hepatic triglyceride lipase activity. AB - We quantified serum lipids and postheparin plasma lipolytic activities in 5 weightlifters presently self-administering androgenic steroids (users) and an equal number not currently using these drugs (non-users). Mean (+/- SD) age (23 +/- 2 vs 25 +/- 4 yr), body weight (102.7 +/- 11.4 vs 86.8 +/- 13.6 kg), and percent body fat (8.6 +/- 2.5 vs 7.8 +/- 6.0%) were not different in users and non-users, respectively. Similarly, there were no differences in total cholesterol (183 +/- 27 vs 176 +/- 32 mg.dl-1) low-density lipoprotein cholesterol (138 +/- 25 vs 108 +/- 32 mg.dl-1), or triglyceride (93 +/- 26 vs 93 +/- 41 mg.dl-1) levels in the two groups. High-density lipoprotein (HDL) cholesterol concentrations, however, were significantly lower in the users (26 +/ 10 vs 50 +/- 13 mg.dl-1; P less than 0.05), and most of the difference was due to lower HDL2-cholesterol concentrations (6 +/- 4 vs 22 +/- 9 mg.dl-1; P less than 0.05). Postheparin plasma lipoprotein lipase activity was only slightly lower in the users (3.49 +/- 2.23 vs 5.36 +/- 1.73 mumol FFA.ml-hr-1; P= NS). but hepatic triglyceride lipase activity was significantly higher in this group (27.99 +/- 6.89 vs 11.15 +/- 2.76, mumol FFA.ml-hr-1: P less than 0.001) and correlated inversely with HDL2-cholesterol concentrations (r = -0.81; P less than 0.01). We conclude that androgenic hormones reduce HDL-cholesterol concentrations and the HDL2-cholesterol subfraction, possibly by enhancing hepatic triglyceride lipase activity. PMID- 4033403 TI - Effects of dieting and exercise on lean body mass, oxygen uptake, and strength. AB - The effects of exercise on lean body mass (LBM), fat mass (FM), maximal oxygen uptake (VO2max), and quadriceps (QD) strength were studied in 72 male, mildly obese (X = 38% fat) subjects (X age, 43.5 yr) randomly assigned to one of eight treatments arranged in a 2 X 4 factorial plan with exercise (EX) and non-exercise (NE) and four diets as the two factors. Exercise consisted of a 3 d/wk, 8-wk aerobics program (70-85% maximum heart rate) accompanied by a calisthenics program. LBM was determined by whole body potassium (40K), FM by subtracting LBM from total body weight, VO2max using the Wilmore-Costill method, and QD strength with the Cybex II system. Weight loss of the combined EX (11.8 +/- 0.6 kg) (X +/- SE) and NE (9.2 +/- 0.3 kg) groups was not statistically different. LBM of the EX group was unchanged (from 63.1 +/- 1.9 to 62.5 +/- 2.1 kg), whereas in the NE group it was reduced from 62.6 +/- 1.1 to 59.3 +/- 1.2 kg (P less than 0.001) accounting for 36% of total weight loss. FM loss was greater for the EX group (11.2 +/- 1.5 kg) when compared to the NE (5.2 +/- 1.6 kg) group (P less than 0.001). The EX group exhibited an increase in VO2max from 2.9 +/- 0.3 to 3.4 +/- 0.2 1 X min-1 (P less than 0.001), whereas the NE group was unchanged (3.0 +/- 0.3 to 2.9 +/- 0.4 1 X min-1 (NS].(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4033404 TI - Effect of carbohydrate feeding frequencies and dosage on muscle glycogen use during exercise. AB - Nine men were studied during three 4-h cycling bouts to determine the effect of frequency and dosage of solid carbohydrate (CHO) feedings (86 g) on muscle glycogen utilization and exercise performance. In the frequency trial (F), the subjects ingested 10.75 g of CHO along with 200 ml of water at 30-min intervals; in the dosage trial (D), the subjects ingested 21.5 g of CHO with 400 ml of water at 60-min intervals. During the control trial (C), the subjects ingested 400 ml of an artificially sweetened placebo at 60-min intervals. Respiratory exchange ratios were significantly elevated in both trials D and F (P less than 0.05). Blood glucose was significantly elevated in trial D 20 min post-feeding but had returned to control levels by 50 min. In trial F, blood glucose was maintained at a constant level throughout the entire 4 h. In trial C, blood glucose declined steadily during the entire 4 h. Despite the differences in blood glucose levels between the three trials, there were no significant differences in the rate of muscle glycogen utilization in any of the trials (D = 82.9 +/- 6.6 [SE] mmol X kg 1 vs C = 80.9 +/- 6.9 mmol X kg-1 vs F = 74.4 +/- 12.2 mmol X kg-1). In a sprint ride (100% VO2max) to exhaustion at the end of each trial, the subjects performed significantly longer in trial F compared to C (120.97 +/- 9.6 vs 81.0 +/- 7.1 s).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4033405 TI - Aerobic requirements of overground versus treadmill running. AB - There is general agreement that the oxygen demand of level running is similar for both the treadmill (TM) and overground situations at speeds under 260 m X min-1. However, controversy exists with regard to inclined running. The prevailing view, represented by the ACSM prediction formulas, is that overground hill running is theoretically more costly than inclined treadmill running. This study was designed to investigate the problem from an empirical standpoint. Seven male subjects performed overground and TM running at two grades (0 and 5.7%) over a range of speeds between 136-286 m X min-1. For the outdoor trials, subjects covered a distance of 950 m at a constant pace, and expired gas was collected over the last 150 m. Matching trials were then performed on the treadmill at the same speed and % grade. Regression lines were calculated for speed vs oxygen consumption (VO2). For TM and overground level running, these were: VO2 (ml.kg 1.min-1)= 0.222 X speed (m.min-1) - 1.33 and VO2 (ml.kg-1.min-1) = 0.202 X speed (m.min-1) + 3.21 respectively. The regression lines from TM and overground inclined running were: VO2 (ml.kg-1.min-1) = 0.237 X speed (m.min-1) + 7.53. and VO2 (ml.kg-1.min-1) = 0.233 X speed (m.min-1) + 7.78 respectively. A 2 X 3 X 2 ANOVA revealed that the differences between mean values for VO2 for level TM running vs level overground running and grade TM running vs grade overground running were not statistically significant (0.10 less than P less than 0.25).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4033406 TI - Aerobic/calisthenic and aerobic/circuit weight training programs for Navy men: a comparative study. AB - Study I. Participants were 43 Navy men (mean age = 32.1 yr) assigned to one of three exercise training protocols: aerobic/circuit weight training performed at either 40 or 60% of determined one-repetition maximum strength or aerobic/calisthenic training. During the 10-wk study, each exercise group participated in three training sessions per week performed on alternate days. The results of this study indicate that dynamic strength (both upper and lower) increased for the aerobic/circuit weight training groups but not for the aerobic/calisthenic group. With the exception of bench press endurance for the aerobic/calisthenic group, all groups showed significant increases in muscular endurance and stamina. No significant changes were seen in static strength or flexibility in any of the groups. Study II. Subjects were 87 male Navy personnel (mean age = 19.8 yr) receiving basic training at the Recruit Training Command, San Diego, CA. One company of recruits (N = 41) participated in an experimental aerobic/circuit weight training program at 70% of determined one-repetition maximum. A second company (N = 46) received the standard Navy recruit physical training program (aerobic/calisthenic training). During the 8-wk study, both groups participated in an identical running program performed three times per wk on alternate days. Additionally, aerobic/circuit weight training participants completed two circuits (1 circuit = 15 exercises) three times per wk on alternate days to running. Study findings show the experimental aerobic/circuit weight training program produced significantly greater dynamic muscular strength and muscular endurance changes than the standard aerobic/calisthenic program.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4033407 TI - Movements and the flow of lymph. PMID- 4033408 TI - Angular velocities, linear velocities, and kinetic energies of a number of female rowers. PMID- 4033409 TI - Skeletal complications of Gaucher disease. AB - Gaucher disease is a collection of related disorders of sphingolipid catabolism caused by the deficiency of a specific beta-glucosidase. The inefficiency of this enzyme, glucocerebrosidase, to degrade its natural substrate leads to the accumulation of the complex lipid glucocerebroside in tissue macrophages. The pathogenesis of the disease is, as yet, poorly understood. The manifestations of the disease are protean with hepatosplenomegaly and bone deterioration frequently the predominating signs. The disease most frequently causes disability because of its effects on the skeleton. This review seeks to summarize the current clinical understanding of these complications. Experience with 327 patients reveals that the bone disease in this disorder is extremely variable. The severity of the problems range from asymptomatic persons with neither radiographic, scintigraphic, nor histologic evidence of bone involvement to those whose skeleton is completely devastated by a process of osteopenia, osteonecrosis, and osteosclerosis. These severely affected individuals show the most bizarre deformities in their bones and are subject to pathologic fracture. Most patients fortunately, are less profoundly affected, but many are plagued by bone pain of an arthritic nature or by an acute prostrating bone crisis probably best described as a bone infarction. The accepted etiology that these crises are a result of vascular compromise produced by occlusion of vessels by Gaucher cells is not supported by scintigraphic or histologic studies. Moreover, the vascular hypothesis does not explain the variety of lesions of the skeleton seen in this multifocal bone disease. Preliminary metabolic and endocrinologic studies suggest that this is not a systemic disorder of metabolism which affects bone uniformly. On the contrary, the lesions are multiple and localized, and sometimes much of the skeleton is preserved. These observations suggest that bone is affected because of collections of Gaucher cells scattered throughout its substance and may be the result of a toxic process around these foci. Alternatively, the storage of glucocerebroside in tissue macrophages may disturb the generation of competent osteoclasts and thus result in a failure to maintain a healthy skeleton. Further research is needed to delineate the pathogenesis of this disorder before any effective therapy can be developed. PMID- 4033410 TI - The Guillain-Barre syndrome: pulmonary-neurologic correlations. AB - In a retrospective analysis of 40 hospitalized patients with the Guillain-Barre syndrome (GBS), we related the use and outcome of assisted ventilation to specific quantitative details of the neurologic illness. Two patients had an unusually prolonged course: they were ventilated for 374 and 396 days before successful weaning. The other 38 patients were similar in most respects to those in previously reported series. Sixteen ventilated patients were hospitalized 56.6 +/- 10.6 (mean +/- S.E.M.) days, were ventilated 27.9 +/- 6.5 days, and had primarily pulmonary complications. There were 4 deaths during ventilation, and 9 of 13 survivors (69%) had a short-term excellent functional neurologic outcome. Attention to the neurologic details of the course of illness may spare some patients from tracheostomy. Twenty-two patients not requiring respirator support suffered distinctly less severe neuromuscular impairment with minimal cranial neuropathy, had no occurrence of pneumonia, and were discharged after 19.1 +/- 4.6 days. Eighty-one percent had an excellent functional outcome. The wide range of manifestations and severity of patients with GBS requires the attending physician to be flexible in dealing with each case and not make management decisions arbitrarily, by reference to a hypothetical "typical case." PMID- 4033411 TI - Pulmonary cavitation following pulmonary infarction. AB - Cavitation following bland pulmonary infarction is not commonly considered in the differential diagnosis of cavitary lung disease. In a 4-year period we have found 10 cases of cavitating pulmonary infarction (CPI) by reviewing serial chest radiographs from autopsies with pulmonary infarction and in all cases with positive ventilation-perfusion lung scans. We have compared these cases to 31 previously reported cases in the English literature that met our criteria for CPI. In our 10 patients, there were 12 radiographic cavities; 5 in the upper lobes, 5 in the lower lobes and 2 in the middle lobe. This distribution was consistent with a relative upper-lobe predominance in the literature review. In nine patients the cavitation appeared rapidly (mean, 5 days) and was associated with fever, purulent sputum, and leukocytosis. Sputum cultures were obtained in eight patients, revealing Pseudomonas aeruginosa and Escherichia coli in three each and Proteus species in two. In four patients, pulmonary infarction was not considered and the diagnosis was made at autopsy, a situation also common in previously reported cases. We have seen a high incidence of CPI in a retrospective review of patients with pulmonary infarction, and we believe that it is important to consider this diagnosis when evaluating cavitary lesions. PMID- 4033412 TI - Liver involvement in sickle cell disease. AB - In an effort to clarify the features of hepatic dysfunction in sickle cell disease, we obtained serial tests of liver function in 100 consecutive patients with sickle cell anemia and in 30 consecutive patients with hemoglobinopathy SC during a five-year period. There were 32 patients with chronic abnormalities in tests of liver function. These abnormal tests were explained by a variety of lesions in 30 cases, and the liver disease remained unexplained in only 2 patients who declined liver biopsy. The diagnoses in these 30 patients included hepatitis, chronic passive congestion, common duct obstruction, alcoholic liver disease, pregnancy, collagen-vascular disease, and sarcoidosis. Evidence for hepatitis B infection was present in 19 of those with sickle cell anemia and in 6 of those with hemoglobinopathy SC. The bilirubin levels in sickle cell anemia appeared to have a trimodal distribution, with six patients exhibiting markedly elevated levels of indirect bilirubin suggesting a difference in bilirubin metabolism. There was no evidence of liver disease in 72 patients with sickle cell anemia, nor in 24 patients with hemoglobinopathy SC, as these patients exhibited only mild elevation of their serum indirect bilirubin levels owing to chronic hemolysis. Intrasinusoidal sickling and Kupffer cell erythrophagocytosis were nearly universal findings at liver biopsy, irrespective of the clinical disorder, and were not related to the degree of liver test abnormalities. Liver and biliary tract dysfunction in sickle cell disease have been attributed to anoxia secondary to sinusoidal obstruction by sickled erythrocytes and Kupffer cell erythrophagocytosis. However, some causes of liver disease in sickle cell patients can be explained by clinical disorders other than the hemoglobinopathy alone.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4033413 TI - The effect of a prior presentation on temporal judgments in a perceptual identification task. PMID- 4033414 TI - Integration versus decomposition in the retention of complex ideas. PMID- 4033415 TI - Effects of constraint and validity of sentence contexts on lexical decisions. PMID- 4033416 TI - Script processing in a natural situation. PMID- 4033417 TI - Interaction of stimulus and contextual information during reading: identifying words within sentences. PMID- 4033418 TI - Continuous monitoring of human contingency judgment across trials. PMID- 4033419 TI - Scale effects in memory for the time of events. PMID- 4033420 TI - Representation in the mental lexicon: implications for theories of the generation effect. PMID- 4033421 TI - Diabetic osteopenia and circulating levels of vitamin D metabolites in type 2 (noninsulin-dependent) diabetes. AB - The degree of diabetic osteopenia and serum vitamin D metabolite levels were measured in 168 type 2 (noninsulin-dependent) diabetic patients. Based on six indices obtained by microdensitometry, we found the bone mass in 26.2% of diabetic patients to be clearly decreased and in 11.9% to be severely decreased. Our direct method of analysis of bone mass shows that diabetic osteopenia differs from typical osteoporosis in character. In addition, serum 24,25-dihydroxyvitamin D was significantly decreased (P less than 0.01), but 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D were similar to those of controls. PMID- 4033422 TI - Adipocyte precursor cells in obese and nonobese humans. AB - Adipose precursors isolated from the stromal-vascular fraction of omental and subcutaneous adipose tissue, from defined hyperplastic obese and nonobese human adults were cultured in order to measure and compare replication rates. After multiplication to confluence these cells were also cultured in an enriched viscous suspension medium to optimize the expression of these cells to adipocytes, allowing an estimation of the number of cells having the ability to express an adipocyte phenotype. No difference in replication rate was seen between obese and nonobese donors or when adipocyte precursors from different depots were compared. When cells were allowed to develop fully in the enriched medium, approximately 6.5% of the original inoculated cell population exhibited an adipocyte morphology. Thus, these results suggest that environmental rather than genetic factors may be responsible for the hyperplasia seen in certain massively obese humans. Furthermore, the results indicate that fat-free cells found within the stromal-vascular fraction of adipose tissue have the ability to develop into adipocytes. However, it is suggested that the relatively low yield in obtaining fully differentiated fat cells under these conditions may be due to the heterogeneity of adipose related cells within the original stromal-vascular fraction from which these cultures were initially derived. PMID- 4033423 TI - Leucine metabolism in thyrotoxicosis: plasma aminogram and 3-methylhistidine excretion before and after treatment. AB - Previous studies have suggested increased protein catabolism and altered muscle metabolism in hyperthyroid patients. In this experiment we investigated parameters of protein and leucine metabolism before and after treatment of hyperthyroidism. While confined in a metabolic ward, patients' daily caloric intake was based on the resting energy expenditure and an allowance for 16 hours of light physical activity. We found no significant difference in plasma aminogram and urinary 3-methylhistidine excretion (an index of protein catabolism) before and after treatment. On the other hand, hyperthyroidism appeared to increase the rates of oxidation, turnover, and plasma clearance of endogenous leucine. However, only the 60% increase in the rate of leucine oxidation was statistically significant. We conclude that in spite of increased catabolism, basal levels of branched-chain amino acids are well maintained in plasma of hyperthyroid patients consuming a diet that compensates for their hypermetabolic state. PMID- 4033424 TI - Plasma lipoprotein abnormalities associated with acquired hepatic triglyceride lipase deficiency. AB - Two enzymes, lipoprotein lipase (LPL) and hepatic triglyceride lipase (HTGL), are released into human plasma after intravenous injection of heparin. LPL is the major enzyme responsible for initiating catabolism of chylomicrons and very-low density lipoproteins (VLDL). The physiological role of HTGL is less certain. HTGL has been postulated to be an alternate enzyme to LPL in hydrolysis of triglyceride in VLDL and to be an important enzyme for removal of phospholipid from both low-density lipoproteins (LDL) and high-density lipoproteins (HDL). In this latter role, this enzyme would convert larger, lighter lipoprotein particles to smaller denser particles. HTGL deficiency has been found in severe liver disease and with a genetic deficiency of this enzyme. A unique patient is described with acquired hepatic triglyceride lipase deficiency and vitamin A intoxication. This patient developed hypercholesterolemia with an increase in both LDL and HDL. An increased proportion of lighter LDL (LDL1) and HDL (HDL2) was noted. In addition, after administration of heparin there was no shift in the distribution of apoE in plasma fractionated using a column containing 4% agarose. These findings are consistent with a postulated role of HTGL in metabolism of light LDL and HDL particles and some classes of apoE containing lipoproteins. PMID- 4033425 TI - Effect of increased physical activity on voluntary intake in lean women. AB - To determine the effect of exercise-related factors on food intake, five nonobese women (mean +/- SEM of the percent of desirable body weight, 97 +/- 5) were hospitalized as part of a metabolic experiment. Excess amounts of a mixed food diet were provided on platters to the subjects. They served themselves from these and ate freely. Intake was estimated covertly by weighing the platters before and after serving. Expenditure was monitored with daily activity diaries and indirect calorimetry determinations of all the activities recorded. After a five-day evaluation phase, each subject underwent three 19-day treatment periods in which physical activity was modified. Total daily expenditure was increased to 114 +/- 4% of the sedentary treatment for a mild exercise period and 129 +/- 3% for a moderate period. Corresponding voluntary intakes during exercise were 117 +/- 5% and 122 +/- 6% of sedentary treatment. Although moderate exercise (mean 772 +/- 40 kcal/d) was greater than mild (378 +/- 63 kcal/d), the increased intake levels of the two were comparable. However, the resulting energy balances of 10 +/- 71 kcal/d for sedentary, 64 +/- 43 kcal/d for mild and -116 +/- 92 kcal/d for moderate treatments were not different. Therefore, in a paradigm which permits maintenance of a voluntary balanced energy state during an inactive period, compensatory intake responses to exercise occur. Unlike obese women who do not match their intakes to energy expended as physical activity, nonobese women demonstrate hyperphagic responses. PMID- 4033427 TI - Normal plasma free amino acid values in adults: the influence of some common physiological variables. AB - We measured plasma free amino acids in ten healthy adults (five males, five females, ages 26 to 54 years), at four times of day, under two dietary protocols. The design allowed us to measure the effects of some common physiological variables on the metrical distributions (mean, SD, skewness, kurtosis) of 80 values (in most cases), for each of 20 amino acids. Analysis of variance indicates that individuals in a "public" population possess "private" phenotypes for 18 plasma amino acids under typical external experiences; the exceptions were aspartate and taurine. The collective infradiem variation rarely exceeded 50% of the nadir value for any amino acid. We conclude that genotype is an important determinant of plasma amino acid phenotype in normal persons, and that there is striking homeostasis of plasma amino acid values in human adults adapted to normal daily activity. PMID- 4033426 TI - Time course of changes in gluconeogenesis from various precursors in chronically endotoxemic rats. AB - Rates of gluconeogenesis (GNG) from lactate and triosephosphate precursors were measured in hepatocytes isolated from rats that have received endotoxin or physiological saline by continuous infusion from an implanted pump. Six hours after the onset of infusion (day 2 postsurgery) GNG from lactate was significantly elevated in hepatocytes of endotoxemic (ET) animals. By 24 hours later, the gluconeogenic rate was depressed, compared to cells of NaCl-infused controls. However, providing ET cells with lactate at concentrations found in the in vivo milieu resulted in glucose production at rates not different from those of control cells incubated at their respective in vivo (lower) substrate levels. On day 2 postsurgery, ET rats were hyperglycemic and hyperlactacidemic; on day 3 the elevated blood lactate concentration was maintained, but the plasma glucose values were not different from those of NaCl controls. The glucagon-induced increment in glucose synthesis was depressed in cells of ET rats both on day 2 and day 3 postsurgery, although the total amount of glucose released was significantly less only on day 3. The pattern of norepinephrine stimulation was similar to that of glucagon, except for the increase above the basal rate of GNG on day 3 being the same for control and ET cells. GNG was also assessed from oxidized substrates (fructose (F) and dihydroxyacetone (DHA] and reduced substrates (sorbitol and glycerol) entering the pathway at the triosephosphate level. On day 2 both cell populations produced glucose from each of the four precursors at comparable basal rates.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4033429 TI - Adipocyte precursor clones vary in capacity for differentiation. AB - Adipocyte precursor populations derived from rat perirenal or epididymal fat were found to be composed of clones varying in capacity for differentiation. Perirenal tissue contained a greater proportion of those clones that differentiated extensively. It is hypothesized that differences between regions and individuals in growth of adipose tissue may be due to differences in the frequency within adipocyte precursor pools of clones with unusual capacities for replication and differentiation. PMID- 4033428 TI - Prolactin and growth hormone responses to dermorphin in patients with prolactin secreting pituitary adenoma. AB - We have recently shown that dermorphin (D), a new potent opioid peptide (H-Tyr-D Ala-Phe-Gly-Tyr-Pro-Ser-NH2) stimulates prolactin (PRL) and growth hormone (GH) secretion in humans. In 11 patients with a PRL-secreting pituitary adenoma (eight microprolactinomas and three macroprolactinomas with suprasellar extension), diagnosed by pituitary dynamic function tests, and radiological evidence with confirmation at surgery, the PRL and GH responses to D were studied to evaluate the effect of pathological hyperprolactinemia on the opioid-induced secretion of GH and PRL. No PRL response to D was observed in all 11 patients. Plasma GH increased after D in all patients, except in three patients bearing a macroprolactinoma. This study shows that the effect of D on PRL and GH secretion can be dissociated in patients with PRL-secreting pituitary adenoma, perhaps for a different derangement in the hypothalamic-pituitary mechanism(s) underlying the opioidergic regulation of GH and PRL secretion. In addition our data indicate that D can be employed as a useful opioid probe in humans. PMID- 4033430 TI - General carotenoid methods. PMID- 4033431 TI - Gas chromatography of isoprenoids. PMID- 4033432 TI - High-performance liquid chromatography of carotenoids. PMID- 4033433 TI - Invertebrate carotenoproteins. PMID- 4033434 TI - Separation of mevalonate phosphates and isopentenyl pyrophosphate by thin-layer chromatography and of short-chain prenyl phosphates by ion-pair chromatography on a high-performance liquid chromatography column. PMID- 4033435 TI - Reversed-phase high-performance liquid chromatography of C5 to C20 isoprenoid benzoates and naphthoates. PMID- 4033436 TI - Lecithin-cholesterol acyltransferase and cholesterol transport. PMID- 4033437 TI - A comparison of methods for the identification of sterols. PMID- 4033438 TI - Side-chain cleavage of cholesterol by gas chromatography-mass spectrometry in a selected ion monitoring mode. PMID- 4033439 TI - Ecdysone conjugates: isolation and identification. PMID- 4033440 TI - High-performance liquid chromatography of bile acids. PMID- 4033441 TI - Mass spectrometry of bile acids. PMID- 4033442 TI - On the mathematical basis of Zelen's prerandomized designs. PMID- 4033443 TI - Comprehensive Cohort Study: an alternative to randomized consent design in a breast preservation trial. PMID- 4033445 TI - Morphologic analysis of compound words. PMID- 4033444 TI - On priming medical students in medical informatics. PMID- 4033446 TI - Mitochondrial membrane potential in lymphocytes as monitored by fluorescent cation diS-C3-(5). AB - A lipophilic fluorescent cation diS-C3-(5) and rotenone suppress the oxygen consumption rate of thymocytes in similar concentrations. Seventy percent inhibition corresponds to an inhibitor:cytochrome a molar ratio of about 1:1. Addition of uncouplers decreases the inhibition of respiration by diS-C3-(5) (but not rotenone). FCCP in similar concentrations increases O2 consumption in the absence of diS-C3-(5) and the diS-C3-(5) fluorescence intensity in the presence of TMPD in thymocyte suspensions. In most thymocyte preparations, oligomycin (0.05-0.1 microgram/mL) increases the fluorescence of diS-C3-(5) and further addition of TMPD (50-100 microM) decreases the fluorescence. Addition of NaCN (400 microM) after oligomycin leads to a fluorescence increase that is hardly affected by subsequent addition of 0.2 microM FCCP. Nigericin (10-50 nM) decreases the diS-C3-(5) fluorescence. The data indicate that the diS-C3-(5) fluorescence associated with mitochondrial transmembrane potential (delta psi m) may be an essential part of the diS-C3-(5) fluorescence in lymphocyte suspensions. The changes of the diS-C3-(5) fluorescence intensity in the presence of TMPD after FCCP addition reflect delta psi m. PMID- 4033447 TI - A preliminary evaluation of the effect of lofexidine on vasomotor flushes in post menopausal women. AB - This is a preliminary study of a new orally administered alpha-adrenergic agonist, lofexidine, to establish its effectiveness in the control of vasomotor flushes (VMF) in five post-menopausal women. The initial dose of lofexidine, 0.1 mg b.i.d., was increased by 0.1 mg b.i.d. every two weeks until VMF disappeared, until side-effects became intolerable, or until a maximum dose of 0.6 mg b.i.d. was reached. When the maximum dose for these criteria was reached, there was a patient-blinded crossover to placebo. Each patient recorded her VMF each day and was monitored by finger thermistor for three hours every two weeks to record VMF. At the maximum tolerated dose, the patients had an average 74% (P less than 0.001) decrease in subjectively noted VMF, and a 61% (P less than 0.05) decrease in VMF objectively measured by finger thermistor. The side-effects (dry mouth, fatigue, headache) became intolerable for one patient at 0.3 mg b.i.d. and for one patient at 0.5 mg b.i.d. Two patients tolerated 0.6 mg b.i.d. Four patients had a return to near baseline numbers of VMF with placebo. Preliminary evidence indicates that lofexidine is probably effective in the treatment of VMF; however, at doses which completely eliminate VMF, the side-effects may become intolerable. PMID- 4033448 TI - Post-menopausal estrogen replacement: the prevention of osteoporosis and systemic effects. AB - The long-term effects of estrogen replacements in post-menopausal women were assessed in 61 estrogen-treated and 63 control subjects followed prospectively for 3-16 yr (mean 8.6 yr). A loss of height of 1.3 cm (1/2") or more developed with twice the frequency among control as among estrogen-replaced subjects, with the major difference appearing after 65 yr of age. However, estrogen replacement was not an absolute protection against height loss, especially after 70 yr of age. Myocardial infarctions and abnormal electrocardiograms were significantly reduced among the estrogen-replaced compared to the control subjects, but further observations are needed. Long-term estrogen replacement in post-menopausal women reduces the development of spinal osteoporosis and may reduce the development of ischemic heart disease. PMID- 4033449 TI - The effects of naloxone infusion and stellate ganglion blockade on hot flushes in the human male. AB - A 77-yr-old man presented with severe episodes of hypotension, flushing and sweating starting immediately after infarcting his only remaining functioning testis. The attacks were shown to be mediated by the cervical sympathetic chain, the reaction on the face and neck being abolished by a stellate ganglion block. The severity and frequency of sweating was also considerably reduced with naloxone as may be seen in female climacteric flushing. Injection of testosterone significantly reduced the frequency and severity of the attacks, which were unaltered by oestrogen treatment. PMID- 4033450 TI - Temporal correlation of some endocrine circadian rhythms in elderly subjects. AB - The aim of this chronobiological study was to investigate temporal correlations in the circadian patterns of 6 hormones, namely somatotrophic hormone (STH), prolactin (PRL), cortisol (F), aldosterone (ALD), insulin (IRI) and C-peptide (CP), assayed in systemic blood serum drawn at 07:00, 10:00, 13:00, 16:00, 19:00 and 22:00 h from an antecubital vein in 19 young subjects (aged 20-29 yr, comprising 10 males and 9 females; and 20 elderly subjects (aged 70-81 yr, comprising 10 males and 10 females). All subjects were sampled on a normal dietary sodium intake (120-140 mEq/24h) while following a social routine of diurnal activity (07:00-23:00) and nocturnal rest (23:00-07:00). Time-qualified data were analyzed by lead-lag correlation and by cosinor analysis. According to the lead-lag correlation findings, it would appear that the correlation which exists between several time-qualified series in young subjects is no longer present in elderly subjects. The circadian rhythms which were found to have lost their temporal correlations with advancing age were those between STH and IRI, STH and ALD, PRL and IRI, PRL and CP, and ALD and CP. It should be noted that the correlation between hormonal rhythms breaks down mainly on account of a peculiar age-related change in the magnitude of the circadian fluctuation. This chronological decline in amplitude led to the conclusion that the senescence of endocrine rhythmic functions is a biological phenomenon characterized by altered circadian variability. PMID- 4033451 TI - High blood pressure and 'ischaemic' ECG patterns in climacteric women. AB - A study to evaluate the prevalence of high blood pressure (HBP) and resting 'ischaemic' electrocardiogram (ECG) patterns in the climacteric was carried out in 494 outpatients aged up to 65 yr. The study group was made up of 91 pre menopausal women, 235 natural post-menopausal women, 91 surgical post-menopausal women and 77 women of advanced reproductive age, who comprised the control group. High systolic and/or diastolic blood pressure values were seen in 26.6% of the overall climacteric group (C), i.e. in 23.1% of the pre-menopausal women (PM); 28.9% of the natural post-menopausal women (NMt); and 24.2% of the surgical post menopausal women (SMt), these frequencies being statistically significant compared to that in the control group (K) (6.5%). 'Ischaemic' ECG patterns (according to the Minnesota Code definition) were observed in 20.3% of the C group, in 22.0% of the PM group and in 27.5% of the SMt group, these rates being statistically significant compared to that in the control group (9.1%). Minnesota Code 4:1 and 5: 1-2 patterns were present in 5.7%, and 4:2 and 5:3 patterns in 14.6% of the C group. A significant correlation was found between HBP (systolic and diastolic) and 'ischaemic' ECG patterns. PMID- 4033452 TI - Gynaecology of middle-aged women--menstrual and reproductive histories. AB - The aim of this study was to investigate menstrual history, reproductive functions, fertility regulation and gynaecological operations is a representative sample of middle-aged women. A sample consisting of 1746 women aged 40-66 was randomly selected. Of those initially selected, a total of 1413 (81%) were investigated. Gynaecological data were acquired by means of questionnaires. Eighty-six percent of menstruating women reported a cycle length of 22-30 days and menstrual flows lasting 4-7 days. The median age at natural menopause was 50.9 yr. The oldest menstruating women were 57 yr old. Curettage had been performed in 53%, and 9% were hysterectomised. Every fourth woman had had three or more children, and 15% were nulliparous. Abortion (spontaneous or induced) was reported by 28% of the women. Of 714 menstruating women, 62% were utilising contraceptive methods, among which barrier or natural methods predominated. Nine percent of women aged 40-44 used combined oral contraceptives. Previous or current use of contraceptive pills was reported by 32% of all the women, and of these 20% had been on the pill for 10 or more yr. PMID- 4033453 TI - Calorimetric analysis of phagocytosis of staphylococcal protein-A/IgG complexes. AB - We have analyzed calorimetrically the phagocytosis of the pseudoimmunecomplexes formed by staphylococcal protein A in presence of serum. Strong thermal effects were recorded during phagocytosis. They appear to be the sum of two distinct heat contributions. We have previously shown that these are the expression of two different non-mitochondrial O2 reduction pathways operating during the metabolic "burst" (Eftimiadi and Rialdi, 1982). Experiments carried out at different protein A/IgG ratios produced quantitatively and qualitatively different power time curves. The data reported here indicate that although the immunoglobulins are essential for the triggering complex to form, the presence of complement is necessary to obtain maximal granulocytic metabolic activation. PMID- 4033454 TI - Interaction of papaverine with covalently closed DNA. AB - Cyclic nucleotides influence viral replication and papaverine, as an inhibitor of phosphodiesterase, also affects the replication of both DNA and RNA viruses through an increase in cAMP levels. Moreover in vitro papaverine affects neither protein synthesis nor several polymerases, while it inhibits DNA synthesis. Static fluorescence studies on the interaction of the drug with ColE1 plasmid covalently closed DNA indicate that the drug binds to the nucleic acid, probably by intercalation. A comparison between the binding characteristics of Papaverine and Actinomycin D is also reported. PMID- 4033455 TI - Hemolytic activity of isolates of Yersinia sp. AB - One hundred and thirty one strains of Yersinia sp. isolated in Italy from 1979 to 1982 were examined for their ability to produce hemolysis on blood agar. Hemolytic activity was shown by seventy four strains on chicken blood agar and rabbit blood agar with 0.5% lecithin at 28 degrees C. No hemolytic activity was shown at 37 degrees C. PMID- 4033456 TI - A new calorimetric technique to analyze bacteria-phagocyte interactions. AB - We have assessed the use of a batch calorimeter in the analysis of bacteria phagocyte interactions. Results obtained using different strains of staphylococci agree with our previously reported flow calorimetric data. Phagocytosis of Staphylococcus aureus produces a greater metabolic activation energy expenditure with respect to other "saprophytic" staphylococci. The results obtained indicate that the batch calorimeter better fulfills all the requirements for routine phagocytosis assay. PMID- 4033457 TI - Effect of saccharin on growth and acid production of glucose-grown pathogenic and oral bacteria. AB - Growth and acid production of glucose-grown Gram-positive and Gram-negative rods as well as cocci from the human oral cavity were studied in the presence of 0.02 to 20.00 mg/ml sodium saccharin. All Gram-positive rods, i.e. Actinomyces viscosus, Lactobacillus acidophilus, Bacillus subtilis and Corynebacterium diphtheriae, and Gram-positive cocci, i.e. Streptococcus spp, Staphylococcus aureus and Micrococcus luteus, were significantly inhibited by saccharin, especially at the higher concentrations. While Gram-negative cocci, i.e. Veillonella sp and Neisseria sicca were strongly inhibited by all tested saccharin concentrations, Gram-negative rods, i.e. the enterics and Acinetobacter sp, exhibited little if any inhibition. Saccharin caused a significant reduction in fermentative acid production congruent with observed growth. PMID- 4033458 TI - Change in the volatile fatty acids content of laboratory stored sterilized and non-sterilized swine wastes. AB - The influence of urine and microbial activity was studied as possible factors leading to the generation of volatile fatty acids in non-sterilized stored swine wastes. Urine was found to promote the generation of the volatile acids. The microbial origin of the volatile acids in the wastes was ascertained by the growth of an anaerobic bacterial strain (Peptostreptococcus anaerobius). Significant generation and transformation of these acids was observed in sterilized swine waste samples stored under conditions similar to the non sterilized samples. PMID- 4033459 TI - Antimicrobial activity of some heterocyclic derivatives of 1-methyl-1-nitroethyl sulphides. AB - The minimum inhibitory concentration values for a group of synthesized heterocyclic derivatives of 1-methyl-1-nitroethyl sulphide were determined for Gram-positive and Gram-negative bacteria, yeast, and fungi. The active compounds were further screened. The effect of these compounds on growth, morphology and incorporation of 3H-uridine was also tested. Comments on the possible model of action of such compounds is included. PMID- 4033460 TI - Eight suggestions toward easing the crisis. PMID- 4033461 TI - Tort system abuses at the heart of crisis. PMID- 4033462 TI - Insurance official explains carrier's rates and reserves. PMID- 4033463 TI - PICOM chief tells that carrier's story. PMID- 4033464 TI - Malpractice crisis threatens health care for Detroit's homeless. PMID- 4033465 TI - This crisis could worsen Detroit's infant mortality. PMID- 4033467 TI - Potentiality of artificial sea water salts for the production of carrageenase by a marine Cytophaga sp. AB - Production of an extracellular enzyme complex (carrageenase) was studied by examining cell-free fluids from cultures of a marine Cytophaga, 1k-C783, growing on different media. Among artificial sea water salts, only NaCl and MgCl2 were utilized by the organism to produce carrageenase. The minimal concentrations of suitable combinations of NaCl and MgCl2 were found to be 0.05 M NaCl plus 0.25 M MgCl2, and 0.15 M NaCl plus 0.15 M MgCl2. KCl and CaCl2 did not have any role in carrageenase production in ZoBell 2216 E broth medium. Carrageenase was synthesized continuously within the resting cells and was released from the cells as well as in the growing cells, when nutrient had been supplied. PMID- 4033466 TI - Fatty acid composition and Shwartzman activity of lipopolysaccharides from oral bacteria. AB - The composition and the nature of the linkage of fatty acids and the Shwartzman activity of lipopolysaccharide (LPS) preparations derived from oral gram-negative bacteria including Bacteroides gingivalis, Bacteroides loesheii, Eikenella corrodens, Fusobacterium nucleatum, and Actinobacillus actinomycetemcomitans were examined. 3-Hydroxylated and nonhydroxy fatty acids of various chain lengths were found in all of the LPS preparations. All nonhydroxy fatty acids were found to be ester-bound, and part of the 3-hydroxy fatty acids in the LPS of B. gingivalis, E. corrodens, F. nucleatum, and A. actinomycetemcomitans were shown to be involved in ester linkage. It was also suggested that the hydroxy group of the ester-bound 3-hydroxy fatty acid of the LPS of F. nucleatum and A. actinomycetemcomitans is at least partly substituted by another fatty acid, but in the LPS of B. gingivalis and E. corrodens it is not. The main amide-linked fatty acid of the LPS of B. gingivalis, E. corrodens, F. nucleatum, and A. actinomycetemcomitans was 3-hydroxyheptadecanoic, 3-hydroxydodecanoic, 3 hydroxyhexadecanoic, and 3-hydroxytetradecanoic acid, respectively. The results of the Shwartzman assay showed that the E. corrodens LPS was the most active among the preparations tested, and that the Shwartzman toxicity of Bacteroides LPS is extremely low. PMID- 4033468 TI - A staphylococcal coagglutination test for detecting and serogrouping Legionella pneumophila. AB - For detection of Legionella pneumophila and determination of its serogroup, the modified staphylococcal coagglutination test was studied in detail. Cross reactions in serum-agglutination tests were observed among serogroups, but immunoglobulin-coated staphylococcal cells could detect L. pneumophila with high sensitivity (a cell concentration with an absorbance of 0.008 at 660 nm could be detected) and serogroups could be determined without cross-reactions. Moreover the coexistence of other bacteria did not affect the results of the test. These results suggest that the staphylococcal coagglutination test is useful for detection and identification of Legionella, especially in environmental samples, and for serogrouping of isolates of L. pneumophila from clinical specimens. PMID- 4033469 TI - Mycobacterium thermoresistibile from dust of Japanese houses. PMID- 4033470 TI - [The fungal flora of the air in the villages around Carsamba, Northern Turkey]. AB - The fungal flora of the air was investigated in 13 villages of Samsun, Carsamba, Kizilot Health Center in December and February. In most of the villages, Penicillium and Alternaria were isolated most frequently. Scopulariopsis and Fusarium were also found at high quantity in the air. PMID- 4033471 TI - [Importance of vaccination and bacteriological studies in diphtheria epidemics]. AB - The Ouchterlony - Elek gel diffusion test was performed in twenty-nine patients having a positive culture result for diphtheria bacilli on Loeffler and tellurite agars in January and February, 1984 and toxin production was detected in 20 of them. Except one adult patient, the cases ranged in age 2 and 12 years. In 14 patients who have received at least one immunization with diphtheria vaccine had no complication, besides three patients without immunization in whom two received antibiotics plus antitoxin therapy had carditis and soft palate paralysis. Five patients in the non-immunized group and 6 patients in the group received at least one immunization had diphtheritic membrane. In spite of three patients with cardiac and neural complications, with early diagnosis and beginning therapy with antibiotics and antitoxin before the result of in vitro toxigenicity test, O% mortality rate was obtained. PMID- 4033473 TI - [Halophilic bacteria]. PMID- 4033472 TI - [A case of Cryptococcus neoformans meningitis]. AB - In this paper, a fatal Cryptococcus meningitis has been reported. This type of meningitis is quite rare in this country. PMID- 4033474 TI - [Salmonella serotypes isolated in Turkey to the end of 1984]. AB - 59 Salmonella serotypes which belong to A, B, C1, C2, C3, D1, E1, E4, F, G1, H, I, M, P, Q and U groups of Kauffmann - White schema were isolated in Turkey until the end of 1984. PMID- 4033475 TI - Neuroleptic malignant syndrome and the opioid system. AB - Neuroleptic malignant syndrome is a rare and potentially fatal condition occurring usually in patients on long-term neuroleptic medication. The pathogenesis of the syndrome is poorly understood, but appears to be related to central dopaminergic dysfunction. Recently, an opioid-dopamine link has been demonstrated. This paper discusses evidence supporting an opioid dysfunction in the pathogenesis of neuroleptic malignant syndrome. PMID- 4033476 TI - Simplicity--the key to fruitful medical research. AB - Medical research is here divided into two broad categories. The great majority of research is "complex" and includes all studies of intricate body mechanisms. A minority of research is "simple" and deals mainly with direct relationships between human environmental or life-style factors and disease incidence (or with analogous studies on animals). In addition, it includes studies of simple body mechanisms. Examples are provided to demonstrate that most of our medical knowledge of practical benefit derives from simple research. This is particularly the case in the area of prevention. PMID- 4033477 TI - Polyvinyl pyrrolidone-iodine as an intravenous antiseptic. PMID- 4033478 TI - Could supplementary dietary tryptophan prevent sudden infant death syndrome? AB - Rapid eye movement (REM) sleep seems to protect infants from developing the sudden infant death syndrome (SIDS). A biological rhythm involving the locus ceruleus and the dorsal raphe nucleus has been related to melatonin and REM sleep. The same rhythm is present in the medial parabrachial nucleus which is an oscilator for pneumotaxic activity. Tryptophan has been shown to be effective in some adult sleep apneas and to increase REM sleep in infants. Tryptophan - serotonin - melatonin deficiencies are suggested as a possible cause of SIDS. PMID- 4033479 TI - The impact of integrated and intelligent sensor systems on medical equipment and methods. PMID- 4033480 TI - Medical applications of fiberoptic sensors. AB - The key requirements of receptor biomolecules for use in affinity optodes are 1) totally reversible binding, 2) rapid equilibration (on the order of minutes or less), 3) no destruction of the analyte or competing analyte, 4) high differential selectivity (binding constants) for analytes of similar structures, and 5) long-term stability. An obvious first choice for sources of receptors for biosensors is antibodies; these immunoproteins are easily derived for drugs, metabolites, and hormones. However, most of the antibodies selected for immunoassay purposes have very high binding constants for their analytes, which may be the result of very slow dissociation rates. Thus, antibodies to be used in biosensors should be screened for high dissociation rates. Monoclonal antibodies appear to be the most suitable from this point of view. PMID- 4033481 TI - Chemical biosensors and on-line patient monitoring. PMID- 4033482 TI - Biosensors and the clinical laboratory. AB - Aside from the economic factors that make biosensors attractive, on-board signal conditioning and signal processing improve the limits of detection and simplify use of the devices. The present discussion summarizes the breadth of biosensor design and application, and the requirements of clinical assay detection. Current sensor research is aimed toward extending the lower limits of detection for nonradioactive immunoassays. The clinical laboratory is in a state of change; operating and instrumentation costs will affect the delivery of diagnostics. Technology will assume a major role in reshaping the clinical laboratory. Biosensors promise to deliver the diagnostic tools for the evolution that is now in progress. The clinical laboratory will no doubt continue to perform chemical profiling and the more specialized tests. The successful implementation of solid state sensor technology promises to simplify immunoassay procedures, as the autoanalyzer did some 20 years ago for the profiling of blood metabolites. It is likely that more tests will be performed in physicians' offices with the advent of highly automated and cost-effective biosensors. By the use of this technology, practitioners of critical care medicine will be able to assume greater responsibility for diagnostic testing. PMID- 4033483 TI - An inspiration-triggered delivery system for oxygen therapy via a nasal cannula. AB - Therapy for severe chronic lung disease currently includes the administration of supplemental oxygen to prevent breathlessness and tissue hypoxia. Although effective, this therapy is unnecessarily costly, because oxygen is administered to the patient during expiration as well as inspiration. To eliminate this inefficiency, a delivery system that senses the inspiratory effort and delivers oxygen to the patient only during inspiration was developed. The 11 X 5 X 8-cm flow control unit attaches easily to a portable oxygen supply. The components of the system have an expected life of five years, and the 9-V battery provides power for about one month of use. Manual controls permit accommodation to the respiratory pattern of the patient. Preliminary evaluation of the system showed that its effectiveness in producing tissue oxygenation is similar to that of continuous oxygen systems. The system has potential applications in ambulatory oxygen therapy and in other clinical settings to improve the cost/benefit ratio of oxygen treatment. PMID- 4033484 TI - Gastrointestinal endoscopy outside teaching hospitals. PMID- 4033485 TI - Mental and physical health consequences of disasters. PMID- 4033486 TI - Some health consequences of a natural disaster. AB - A survey of the health and psychosocial problems of all victims of the 1983 South Australian Ash Wednesday Bushfires was carried out 12 months after the disaster. A total of 1526 victims completed an extensive questionnaire that included the 28 item General Health Questionnaire and a self-reporting check-list of specific health problems. The data received indicated a significant increase in stress related conditions, including hypertension, gastrointestinal disorders, diabetes, and mental illness, while the prevalence of nonstress-related conditions such as cancer or urological disease were not increased significantly. Health problems increased during the 12 months following the bushfire and diminished toward the end of that period, but a large number of difficulties remained. Certain disaster experiences, particularly the type of loss suffered, were found to be significantly related to health. PMID- 4033487 TI - Trends in mortality from malignant mesothelioma of the pleura, and production and use of asbestos in Australia. AB - Annual mortality from malignant mesothelioma of the pleura (MMP) in Australia (as represented by ICD8 codes 163.0 and 212.4, and ICD9 codes 163 and 212.4) increased in men aged 30 years and older from about 0.5/100 000 in 1968-1970 to 2.1/100 000 in 1983. Corresponding rates in women varied from 0.1/100 000 to 0.2/100 000 between 1968 and 1980, then rose to 0.3/100 000 in 1983. The rise in MMP mortality in men probably corresponds to the increasing use of asbestos, particularly amosite, in Australia during and after World War II. That production and importation of amosite and crocidolite in Australia reached a peak in 1958 may mean that peak mortality from MMP will not be reached until the 1990s (allowing a 35-year lag period). Substantial increases in importation and later production, of chrysotile in the 1950s, 1960s and 1970s may lead to increases in the incidence of other asbestos-related cancers, not reflected in trends in the incidence of MMP. PMID- 4033488 TI - Nutritional profile of recruits to a fitness programme. AB - Examination of the dietary habits of a group of adults embarking on a two-year fitness programme (the "Adelaide 1000") showed that, although many of their dietary habits were more consistent with national dietary guidelines than those of a comparison community group, their overall intake of nutrients was similar. The major difference was a substantially higher rate of dietary supplementation with vitamin and mineral preparations in the fitness group. The implications of these findings are discussed in relation to public understanding of dietary principles and to the provision of practical nutritional guidance in conjunction with fitness programmes. PMID- 4033489 TI - Electroconvulsive therapy. PMID- 4033490 TI - The 1984 Hunter Oration. PMID- 4033491 TI - Cervical headache. PMID- 4033493 TI - Chorionic villus sampling. PMID- 4033492 TI - Endoscopic balloon dilatation of biliary strictures. AB - The case of a 67-year-old woman who had a long history of recurrent cholangitis after repeated biliary tract surgery, and whose clinical course was complicated by the development of multiple biliary strictures and secondary biliary cirrhosis, is reported. Nasobiliary drainage was used to successfully decompress the biliary system and to control infection during an acute episode of cholangitis. Subsequent endoscopic, hydrostatic balloon dilatation of the major bile-duct strictures resulted in an improvement in her clinical condition which was supported by the results of biochemical tests. PMID- 4033494 TI - Life-style diseases in aborigines. PMID- 4033495 TI - Oestrogen replacement therapy. PMID- 4033496 TI - Vaccination, one; maternal rubella, nil. PMID- 4033498 TI - Communicating with patients. PMID- 4033497 TI - Phenylbutazone. PMID- 4033499 TI - Transient childhood myositis. PMID- 4033500 TI - Facial muscle spasms and clonazepam. PMID- 4033501 TI - Haemophilus in genital tract specimens. PMID- 4033502 TI - C. difficile-associated diarrhoea. PMID- 4033503 TI - Cystic fibrosis. PMID- 4033504 TI - Disturbed behaviour in old age. PMID- 4033506 TI - Head injury predominance: pedal-cyclists vs motor-cyclists. AB - A study of the pattern of head injuries in pedal- and motor-cyclist casualties treated at four teaching hospitals in Melbourne was undertaken to determine whether significant differences occurred between the two groups. The injuries were coded according to the 1980 revision of the Abbreviated Injury Scale of the American Association for Automotive Medicine and the data subjected to statistical analysis. Although motor-cyclist casualties sustained more severe injuries to the body, the results show that pedal-cyclist casualties sustained more frequent and severe head injuries. It is considered that the differences are due, at least in part, to a far lower use of protective helmets among pedal cyclists. Education to increase community awareness of this safety measure followed by legislation for the compulsory wearing of approved safety helmets is urged. PMID- 4033505 TI - Survival of cystic fibrosis patients in South Australia. Evidence that cystic fibrosis centre care leads to better survival. AB - Life tables were calculated for 205 South Australians with cystic fibrosis. An improvement in survival was noted between 1948 and 1982. Ninety-three per cent of patients who were diagnosed as having cystic fibrosis after 1973 were alive at 14 years of age, compared with 40% of those who were diagnosed between 1948 and 1973. A Cystic Fibrosis Clinic was established in 1973 and much of this improvement is attributed to the care provided by this centre. Deaths from meconium ileus fell from 58% of infants with this complication between 1948 and 1973 to only 8% between 1973 and 1983, in spite of the increasing incidence of patients who were chronically colonized with Pseudomonas aeruginosa (currently 68% of patients). These figures are similar to those from Victoria and from other cystic fibrosis centres in North America. The improvement in survival means that adults now comprise a quarter of the patients with cystic fibrosis in South Australia, and that adult institutions need to be aware of these patients and their needs. PMID- 4033507 TI - An elimination diet for chronic urticaria of childhood. AB - Twenty-three children with chronic urticaria were treated with an elimination diet for two weeks. Eighteen completed the period of dietary elimination; in seven of the 18 children there was a marked remission of the urticaria during the second week of the diet. The administration of challenge capsules provoked an exacerbation of urticaria in five of the 14 (36%) children given aspirin. The incidence of reactions to tartrazine, sodium benzoate and yeast (7%) was not significantly different from those to the lactose placebo (9%). In selected cases, elimination diets with controlled reintroduction of foods have a role in the management of chronic urticaria in childhood. PMID- 4033509 TI - Periodontal diseases and smoking. PMID- 4033508 TI - A study of 100 consecutive admissions to a psychogeriatric unit. AB - A series of 100 consecutive admissions to a psychogeriatric unit in a large public psychiatric hospital is described. Fifty-four of these were readmissions. Most of the patients presented with moderate to severe acute psychiatric disorders, and many of these were admitted under detention orders. Their disorders were often readily treatable and most patients returned to their local communities in less than three weeks. Unexpectedly, only one-third of patients had a primary diagnosis of organic cerebral disorder, and few had received a diagnosis from the referring doctor. The principal reason for the referral of patients was that they were obviously severely disturbed and disturbing within their community. Patients who do not cause a disturbance may thus be underdiagnosed and their treatment unnecessarily compromised. The traditional system of health care seems to be working well and in the interests of these psychogeriatric patients and there is no evidence that radical changes are needed. PMID- 4033511 TI - The pain of pleasure. PMID- 4033510 TI - Peer review--a whiff of grapeshot. PMID- 4033512 TI - Abscess of the thyroid gland presenting as a pulsatile mass. AB - Thyroid abscess is a rare disorder, particularly since the advent of antibiotic agents. A case of thyroid abscess, which developed without systemic disturbance, and presented as a pulsatile mass in the neck, is reported. Excision with primary closure was followed by uncomplicated recovery, and is suggested as the preferred form of management. PMID- 4033513 TI - Better Health Commission. PMID- 4033514 TI - Ectopic pregnancy in Queensland. PMID- 4033515 TI - Cautions on correlation. PMID- 4033516 TI - Environmental factors in autoimmunity. PMID- 4033517 TI - Choreoathetosis and alcohol withdrawal. PMID- 4033518 TI - A simple cure for tennis elbow. PMID- 4033519 TI - RSI. PMID- 4033520 TI - Chiropractic revisited. PMID- 4033521 TI - Directional asymmetry. PMID- 4033522 TI - Counter-disaster manual. PMID- 4033523 TI - The cancer-related health check-up. A guide for medical practitioners. PMID- 4033524 TI - [Epidemiology of coronary disease in Italy: current status of the problem]. PMID- 4033525 TI - [State and organization of the prevention of cardiovascular diseases in Italy]. PMID- 4033526 TI - [Socio-occupational factors and coronary disease]. PMID- 4033527 TI - [Intensive coronary care units in Lombardy]. PMID- 4033528 TI - [Follow-up of patients with myocardial infarction]. PMID- 4033529 TI - [Proposal for a registry of cardiovascular diseases in the North Milan area]. PMID- 4033530 TI - [The value of work capacity evaluation in coronary disease patients and their return to work]. PMID- 4033531 TI - [Occupational exposure to styrenes in furniture industry]. PMID- 4033533 TI - [New trends in occupational medicine in relation to chronic degenerative diseases]. PMID- 4033532 TI - [Chronic tracheobronchitis caused by exposure to alabaster and polyester resin dust: 2 case reports]. PMID- 4033534 TI - [The rheologic properties of blood. New findings from circulatory research]. PMID- 4033535 TI - [Cataract surgery and lens implantation. Development, present stage and future perspectives]. PMID- 4033536 TI - [Drug allergy. 2. The clinical syndrome and pseudoallergic reactions]. PMID- 4033537 TI - Influenza prevention for 1985-1986. PMID- 4033538 TI - Isolation of polysomes from permissive and non-permissive invertebrate cell lines infected with chilo iridescent virus. AB - Chilo Iridescent virus (Iridovirus type 6 or CIV) infection results in a disaggregation of the heavy polyribosomes both in permissive and non-permissive invertebrate cell lines. The integrity of the viral genome is not involved in this event, as shown by the polysome absorbance profile on sucrose gradient, prepared from cells infected with UV treated virus. Heavy polysomes reappeared in permissive infected cells during the viral replication cycle. PMID- 4033539 TI - Response rate and survival in myeloma patients receiving prednisone alone. AB - Thirty-two evaluable good risk patients with multiple myeloma received a 70-day tapering course of prednisone beginning at a dose of 1.2 mg/kg/day. Forty-four percent of the patients demonstrated objective evidence of response to this treatment. Although the median time to disease progression for the prednisone treated group was shorter than for patients randomized to receive prednisone with alkylating agents or who were treated with alkylating agent alone, the results from this trial indicate that prednisone, by itself, may produce objective responses. Caution must be used interpreting trials of new agents in myeloma when such treatments are combined with corticosteroid administration. PMID- 4033541 TI - Tumors of unknown origin. AB - Tumors of unknown origin (TUOs) account for 3% of cancers and represent the eighth-most common cancer diagnosis. Although TUOs are commonly classified by their histological presentation, examination of the location of the metastases is equally important. When the histological type and location of metastases are both known, a finite number of common clinical syndromes emerge and one can predict the most common occult primaries. PMID- 4033540 TI - Comparison of stage IV and IV-S neuroblastoma in the first year of life. AB - Clinical staging and factors related to survival were evaluated in 44 stage IV-S and 44 stage IV patients with neuroblastoma, ages 0 to 12 months, seen at Children's Cancer Study Group (CCSG) institutions from 1972 to 1979. In 73 patients with complete surgical staging, the life-table projected survival at 3 years was 91% for stage IV-S and 44% for stage IV. The only deaths in stage IV-S disease occurred in three patients less than 2 months old at diagnosis. In stage IV-S, 3 to 12 months old at diagnosis, the disease-free survival was 97%. Chemotherapy or radiation therapy did not appear to improve the survival rate in stage IV-S. These studies further document a significant clinical and biologic difference between patients with stage IV and stage IV-S neuroblastoma and suggest that they require different therapeutic management. PMID- 4033542 TI - [Effect of biotic factors on the infectivity of ixodid ticks with Coxiella burnetii. 1. The significance of the period of tick feeding for the outcome of infection]. PMID- 4033544 TI - [Effectiveness of the multiyear use of traps in controlling gadflies (Diptera, Tabanidae) in pastures]. PMID- 4033543 TI - [Effect of the concentration and number of Anopheles stephensi larvae on their mortality as affected by Bacillus thuringiensis]. PMID- 4033545 TI - [Characteristics of the acaricidal action of cropotex--an inhibitor of tick development]. PMID- 4033546 TI - [History and status of the problem of the development of methods for formulating the prognosis of malaria, its vectors and other blood-sucking flies in areas of the construction and operation of large hydraulic engineering installations in the Ukraine]. PMID- 4033547 TI - [Fleas in human housing in natural plague foci of the Aral Sea region]. PMID- 4033548 TI - [Diagnosis and treatment of toxoplasmosis at an infectious disease clinic]. PMID- 4033549 TI - [Rheoencephalographic parameters during development]. PMID- 4033550 TI - [Secondary sex ratio in Kac and Kovilj over the past 100 years]. PMID- 4033551 TI - [Relation of the atherosclerosis index and fundus oculi findings in type II diabetics]. PMID- 4033553 TI - [Surgical therapy of carcinoma of the oropharynx]. PMID- 4033552 TI - [Hearing loss in the area of Senta 1978-82]. PMID- 4033554 TI - [Hyperbilirubinemia in recruits from the area of Titov Vrbas]. PMID- 4033555 TI - [Generalized varicelliform herpes zoster]. PMID- 4033556 TI - [Obscure epileptic states in early childhood]. PMID- 4033558 TI - [Case report of myoma of the broad ligament of the uterus]. PMID- 4033557 TI - [Partial pharyngo-laryngectomy in the treatment of isolated stenosis of the hypopharynx]. PMID- 4033559 TI - [The effect of dihydroergotoxin (Redergin tablets, 4.5 mg) on blood pressure and left ventricular function in patients with essential hypertension]. PMID- 4033560 TI - [The gynecologist in the planning of health education in schools]. PMID- 4033561 TI - [Tropical endemic parasitoses: yesterday, today and--probably tomorrow]. PMID- 4033562 TI - [HDL-cholesterol values in childhood]. PMID- 4033563 TI - [Results of Hemoccult screening of 45- to 65-year-old residents of the town of Ada with the goal of early detection of malignant neoplasms of the colon and rectum]. PMID- 4033564 TI - [The effect of emotional stress on diabetes mellitus]. PMID- 4033565 TI - [Prevention of injuries in children with a review of the approach used in Subotica]. PMID- 4033566 TI - [Health education as a continuous activity at all levels of health care]. PMID- 4033567 TI - [Effect of the use of alcohol and smoking on an increase in the number of recurrences during treatment for psoriasis]. PMID- 4033568 TI - [Tumors of the eyelid in the elderly]. PMID- 4033569 TI - [Primary multiple synchronous homologous malignant tumors of the endometrium]. PMID- 4033570 TI - [Artane psychoses]. PMID- 4033571 TI - [A domestic epidemic of botulism--diagnostic problems]. PMID- 4033572 TI - [Illusion and reality in gout]. PMID- 4033573 TI - [Skull fractures in children]. PMID- 4033574 TI - [Endocrinologically-induced changes in the oral cavity during pregnancy]. PMID- 4033576 TI - [Incidence of deviations in body posture in school-age children and young people of various ages]. PMID- 4033575 TI - [Results of a questionnaire method of early detection of breast cancer in the town of Ada in 1982]. PMID- 4033577 TI - [Modern approach to the therapy of depression]. PMID- 4033578 TI - [Ambulatory treatment of cervical polyps]. PMID- 4033579 TI - [Acute infections after cataract surgery]. PMID- 4033580 TI - [Postcoital contraception]. PMID- 4033581 TI - [Tumors of the parotid gland]. PMID- 4033582 TI - Characteristics of cobalt-60 penumbral regions. AB - Ionization chambers with wall materials of various electron densities have been employed to investigate the penumbral region of a cobalt-60 beam of side length 10 cm. Measurements were made in air with chambers of various inside diameters. The homogeneous walls of the ionization chambers were 0.5 g/cm2 in thickness. Extrapolation techniques to zero inside diameter and to infinite density were used, respectively, to eliminate the effect of the inside diameter of the chamber and to determine the penumbral photon-fluence distribution. The method also quantitates both the penumbral primary-dose profiles in water-equivalent media and the degradation of these profiles in media of low electron density. PMID- 4033583 TI - Spectral transmittance and contrast in breast diaphanography. AB - Diaphanography is an imaging technique using transillumination with visible and near-infrared radiation, and a video camera, to diagnose breast disease, including cancer. Originally based on luminance contrast only, there is now interest in false-color multispectral imaging in selected spectral bands to improve tissue differentiation. Some success has been achieved, but the scientific basis for the results was unknown. This research is concerned with measurements of the diffuse transmittance of breast tissues as a function of wavelength in the 600-1060 nm range (and calculations of contrast with a one dimensional diffusion theory model). Carcinoma and glandular tissues were found to have similar spectral transmittances with an increase in transmittance between 750 and 900 nm, and an absorption window around 960 nm. Adipose tissue showed a distinct transmittance minimum at 930 nm. In vivo measurement of an intact normal breast showed a minimum at about 825 nm, as yet unexplained. The transmittance data and reflectance data were used to derive the scattering and absorption coefficients. The diffusion length was also determined from radiance versus depth measurements. These coefficients were used for calculations of contrast in a one dimensional slab model, with and without a layer of cancerous tissue positioned between two slabs of normal tissue. PMID- 4033584 TI - Nuclear resonance scattering measurement of human iron stores. AB - Hepatic iron stores were measured noninvasively in 31 patients (thalassemia, hemodialysis, hemosiderosis, refractory anemia) with suspected iron overload, employing a nuclear resonance scattering (NRS) technique. The thalassemia patients were undergoing desferrioxamine chelation therapy during the NRS measurements. The hemodialysis patients were measured before chelation therapy. Iron levels measured by NRS were in general agreement with those determined in liver biopsies by atomic absorption spectroscopy. In addition, NRS measurements from the thorax of some of these patients suggest that this method may also prove useful for clinical assessment of cardiac iron. PMID- 4033585 TI - Calculation of radiation doses for nonuniformity distributed beta and gamma radionuclides in soft tissue. AB - In cancer radioimmunotherapy nonuniform distributions of radionuclides in geometrically irregular tumor volumes will be encountered. If the tumor is surrounded by a homogeneous layer of soft tissue, the radiation dose distribution in the tumor due to a beta-emitting nuclide can be calculated by convolution of the appropriate Loevinger's point source dose function, J, with the nuclide concentration distribution. Computer programs using fast Fourier transform techniques have been developed to evaluate the three-dimensional spatial convolution accurately and efficiently. Equivalent techniques have also been applied to gamma-emitting nuclides by replacing J in the convolution by the photon point isotropic specific absorbed fraction. Illustrative results are presented for the radiation dose distribution in a 1-ml target volume with activity distribution which is (i) uniform, (ii) limited by diffusion into the target volume, or (iii) limited by diffusion and shedding of radionuclide in the peripheral layers of the target volume. Calculations for the three cases are presented for 32P, 131I, and 15-, 30-, and 100-keV photon emitters. PMID- 4033586 TI - A multiple-pulse sequence for improved selective excitation in magnetic resonance imaging. AB - A new framework for selective excitation that offers simpler design and better performance than conventional excitation methods is introduced. The guidelines for choosing the appropriate radiofrequency (rf) pulse envelope in a conventional selective excitation sequence often rely on Fourier analysis, leading to less than desirable results. Although providing useful insight, Fourier analysis of the rf pulse envelope determines the resultant slice shape accurately only for small flip-angle excitations, and not for larger flip-angle excitations owing to the generally nonlinear behavior of the spin system. In the new excitation framework, additional excitation pulses (typically one) are applied in sequence with the conventional pulse to improve the performance (in phase characteristics and slice definition) over that achieved by the conventional pulse alone. Given a desired spatial spin distribution and an associated rf pulse (e.g., Fourier transform pairs), the Bloch equation is solved backwards to yield the starting distribution required for the conventional pulse to give exactly the desired output. If this residual distribution is a small flip angle away from the actual starting distribution, then Fourier analysis of the residual distribution leads to the necessary "setup" pulse. A gradient of opposite polarity during the setup obviates a refocusing interval after the setup pulse. Computer simulations have verified the efficacy of the multiple-pulse excitation sequence for both 90 degrees and 180 degrees excitations. PMID- 4033587 TI - A new digital tomosynthesis method with less artifacts for angiography. AB - A new nonlinear reconstruction method for tomosynthesis is described. This method is suited for "dilute" objects, i.e., objects in which most of the voxels have negligibly small absorption. Images of blood vessels filled with contrast material approximate this condition if the background is subtracted. The technique has been tested experimentally using a wire phantom and a prepared human heart. The results show significantly less artifacts than the well-known back projection. It is possible to get diagnostic image quality with a few projections. The reconstruction algorithm can be realized with dedicated real time hardware. PMID- 4033588 TI - A simplified approach for modulation transfer function determinations in computed tomography. AB - In order to determine the modulation transfer functions (MTF's) for x-ray computed tomography (CT) scanners, a measurement must be performed to obtain either the point spread function (PSF) or the line spread function (LSF). Thereafter, the usual procedure is to interpolate between the measured points and to determine the Fourier transforms numerically in order to obtain the MTF. Since this must usually be done many times to evaluate various reconstruction kernels and scan modalities, the process is tedious. Fortunately, it can be greatly simplified by utilizing a mathematical function to describe the PSF or LSF. Measured data for five CT scanners indicates that the PSF can usually be described by a Gaussian function. Hence, the MTF can be written in a generalized form eliminating the necessity of performing Fourier transformations each time. The MTF is determined directly from a single performance characteristic related to the full width at half maximum. The accuracy of the approach is compared with detailed MTF calculations for five CT scanners and it is shown to agree favorably with this data. PMID- 4033589 TI - The effect of anode curvature on radiographic heel effect. AB - Previous computer modeling of radiographic heel effect has shown that a simple model can give an accurate representation of heel effect for flat anode surfaces. This paper details the extension of this model to allow curved anode surfaces. A fixed-anode x-ray tube with a demountable anode was constructed and used to test the predictions of the computational model at 25 kVp using stainless-steel anodes. The computer model was also used to estimate the magnitude of the heel effect for a tungsten anode at 60 kVp. This work allows determination of the effect of anode curvature, which is an inherent feature of certain recently proposed tube designs for scanning slit radiography. PMID- 4033590 TI - Quantitative assessment of bone mineral by photon scattering: accuracy and precision considerations. AB - A method to determine the bone mineral density of the calcaneum has been reported earlier by our laboratory. In this method, the calcaneum is irradiated by a 60 keV photon beam from 241Am source and both the coherent and Compton scattered photons are detected by a high-purity Ge detector. The bone mineral density is determined by measuring the ratio of coherent-to-Compton scattered photons. The accuracy and the precision (in vitro) of the method are reported in this paper. The accuracy was determined to be 5%. This was obtained by comparing the bone mineral density values of cadaver calcanea measured directly by Archimedes' volume displacement method with the values measured by the scattering method. The precision was determined to be 3% by measuring the bone mineral density of a calibration phantom intermittently over a ten-month period by the scattering method. PMID- 4033591 TI - Performance of antiscatter grids in diagnostic radiology: experimental measurements and Monte Carlo simulation studies. AB - We have devised an experimental method with which one can accurately measure the transmission of primary radiation and the transmission of total radiation by an antiscatter grid in a setting similar to a practical radiographic examination. We measured the transmission values for 27 combinations of x-ray tube potentials, phantom thicknesses, screen-film systems, and grid parameters. The standard deviation of one measurement was estimated to be 2.9% and 1.5% for the total and primary transmissions, respectively. The measured grid transmission was compared with results predicted by our Monte Carlo calculations; 92% of the measured and calculated values agree within two standard deviations. This close agreement indicates that our Monte Carlo calculation can accurately predict the performance of antiscatter grids under diagnostic imaging conditions. PMID- 4033592 TI - Photodynamic and photohyperthermic response of malignant tumors. AB - This work presents an analytical dosimetry model for photodynamic therapy of malignant tumors. A hyperthermic contribution originating from the absorption of optical irradiation in the tissue may be equally taken into account. The model has been used to analyze tumor response during photodynamic therapy of an in vivo murine tumor. This tumor model was C3H/Tif mammary adenocarcinoma in C3D2F1/Bom mouse strain. PMID- 4033593 TI - Quantitative assessment of bone mineral by photon scattering: calibration considerations. AB - The ratio of the coherent-to-Compton photons scattered from bone can be used to measure its mineral density. Conversion of this ratio (R) to bone mineral density (BMD) requires calibration using bone simulating phantoms. The widely used aqueous solution of K2HPO4 proved unsatisfactory for calibration purposes when using the coherent-to-Compton technique. These solutions differ markedly in their scatter spectra and composition from trabecular bone. In this study a new and more realistic series of phantoms is proposed which simulates well the trabecular bone of the calcaneum. These phantoms are made of bone ash suspended in white petrolatum in varying concentrations. A calibration curve has been established using these phantoms with a range of BMD values of 0 to 347 mg/cm3. The scatter spectra, and range of R values and BMD of these phantoms are in very good agreement with those of real trabecular bone. A measuring device has been built for the determination of the BMD of the calcaneum by using the established calibration curve. PMID- 4033594 TI - Microdensitometry using a slide projector. AB - We have evaluated a simple microdensitometer concept by Stanton et al. for measurements of dose distributions with high spatial resolution. A magnified image of the film is created by a slide projector and its light intensity measured with a photomultiplier with a small aperture. The projector is placed on a movable stage to allow scanning of the film. A resolution of 17 micron (full width at half maximum of the line spread function) was achieved in the film plane. PMID- 4033595 TI - Diagnostic overkill. PMID- 4033596 TI - The statistical analysis of distribution of blood deposits in arterial prostheses after short-term exposure to reduced blood flow in dogs: a computerized study using radioisotopes. AB - This study was undertaken to analyse the distribution pattern of blood elements deposits in 15 cases of vascular prostheses submitted, ex vivo, to reduced blood flow in a canine model. Autologous blood platelets labeled with Indium-111 and human 125 Iodinated fibrinogen were injected into the animals. Ten minutes later, the blood flow in the aorta was reduced to 50 ml/min and the prostheses (Woven DeBakey, 30 cm long and 6 mm internal diameter), were implanted as substitutes for the infrarenal abdominal aorta. The blood flow was then reestablished to 50 ml/min and controlled throughout the entire experiment. When a thrombosis occurred, or after 4 hours of low blood circulation, the prosthesis was collected, weighted and chemically fixed, and the radioactivity was measured by means of a two-channel gamma scintillation counter. These data were then formatted and processed by a special computer program. Final values were processed for graphical representation and analysed statistically. Results show a lack of correlation between weight of thrombotic matrix, platelet accumulation, and fibrin deposits retained from one animal to the other. There is, though, an appearance of a complex interrelationship between the mean pattern of longitudinal distribution of these elements, which shall be qualified as contagious distal accumulation of the deposits. The influence of each animals' blood characteristics, as evaluated by means of regression analysis, account for 40 to 60% of the interindividual variance in blood deposits. Data corrections following evidence of undesirable influences due to uncontrolled parameters are presented. This experimental method permits simultaneous graphical representation of the distribution of several elements in the thrombotic matrix, and at the same time an elaborate numerical analysis of their longitudinal distribution and total accumulation. The method is easy to use, does not require sophisticated equipment, and is less expensive than scintigraphy. PMID- 4033597 TI - An electromagnetic distance measuring system. AB - A new accurate method to determine the myocardial deformation during the cardiac cycle in vivo is described. The system is based upon the mutual inductance principle, yet with transducers which consist of three perpendicular coils, yielding a spherical radiation and sensing characteristic. Thus the system is invariant with regard to rotational movements of the transducers. Residual angle dependences of the transducers can cause deviations of the recorded distance up to 4%. The output voltage is linear with the distance, with an accuracy better than 1%. The frequency response is set to 100 Hz (-3 dB). Zero drift doesn't exceed 0.5% after 24 hours. Measurements are not restricted to radiation propagating media, thus they can be performed in air, inside or outside of any biological object. For studies of regional myocardial performance in the left ventricle spherical transducers were designed with a diameter of 1.5 mm and a measuring range between 5 and 25 mm and flat surface transducers (5 mm diameter, 1.5 mm height) with a measuring range between 15 and 200 mm. PMID- 4033598 TI - The measurement of systolic time intervals. A microprocessor based system for long-term registration of the impedance cardiogram and the systolic time intervals. AB - The systolic time intervals (STI) are reliable parameters for the characterization of left ventricular heart function. The non-invasive methods for the determination of STI are here introduced and compared. The disadvantage of all these methods is their manual evaluation of time intervals which makes a continuous monitoring of STI impossible. Therefore, a microprocessor based system was developed for the automatic registration of STI, stroke time volume (SV) and heart rate from the impedance cardiogram (ICG) and the electrocardiogram (ECG). In this article the preliminary results are discussed of the long-term monitoring of these parameters with the help of this device. PMID- 4033599 TI - Flow resistance of endotracheal tubes during kinking and compression. An experimental study. AB - Kinking and compression of endotracheal tubes may lead to serious problems. Such complications are assumed to occur more often for smaller endotracheal tubes used in adult practise in order to reduce to trauma of intubation. The effect of kinking and compression on the air-flow through PVC endotracheal tubes of various dimensions (inner diameter 6, 7, 8 and 9 mm) and types (manufactured by National Catheters, Portex and Shiley) has been studied in an experimental model. All tubes could be kinked surprisingly much before a measurable flow hindrance occurred. Only small differences were measured between different dimensions and types. In contrast smaller endotracheal tubes were considerable less resistant to edge compression than larger dimensions. PMID- 4033600 TI - Active and passive components of NaCl absorption in the proximal convoluted tubule of the rat kidney. AB - The active and passive components of NaCl absorption were examined in doubly perfused proximal convoluted tubules (PCT) of the rat kidney. When anion concentration gradients were generated by perfusing the lumen with a high chloride, low bicarbonate solution and the peritubular capillaries with a complete solution resembling plasma ultrafiltrate, volume absorption (JV) was 1.79 nl/mm/min and estimated chloride absorption (JCl) was 270 pEq/mm/min. When anion gradients were eliminated by perfusing the peritubular capillaries with a high chloride solution, JV was reduced to 0.91 nl/mm/min and JCl to 140 pEq/mm/min. These residual rates of absorption were reduced to zero by removing potassium from the perfusates. In the presence of anion gradients, removal of potassium reduced JV from 1.79 to 0.60 nl/mm/min and JCl from 270 to 90 pEq/mm/min. It is concluded that: (1) when PCT lumen are perfused with high chloride solution and the peritubular capillaries perfused with an ultrafiltrate like solution, approximately 50% of NaCl and water absorption is passive, driven by the anion gradients, and 50% is active; (2) when PCT lumen and peritubular capillaries are both perfused with high chloride solution, anion gradients are absent and all NaCl absorption is active. PMID- 4033601 TI - Na to Cl permeability in newborn rabbit superficial and juxtamedullary proximal convoluted tubules. AB - It has been previously demonstrated that superficial (SF) versus juxtamedullary (JM) proximal convoluted tubules (PCT) of rabbit have different intrinsic transport characteristics: Na is less permeable than Cl in the latter portions of the SFPCT, while Cl is less permeable than Na throughout the JMPCT. These permeability differences have major influences on the mechanism of salt reabsorption across the proximal tubules. However, both populations of PCT have the same embryological origin. Studies therefore were designed to examine whether two distinct populations of PCT exist at birth or whether a second population of tubules develops with delivery as a result of some unidentified acute change in humoral factor affecting epithelial transport properties. Both morphological and electrophysiological studies were conducted on PCTs from rabbits within 36 h of birth. Both transmission and scanning electron microscopy studies clearly disclosed that SFPCT are less mature than the JMPCT. Also the SFPCT had a lower Na permeability than Cl (0.55 +/- 0.06) while the JMPCT had a higher Na permeability than Cl (1.37 +/- 0.11). Thus these studies demonstrate that intrinsic heterogeneity of PCT is present at birth. Since the SF Na to Cl permeability approximates that of free diffusion these studies suggest that epithelial discrimination in PCT is part of a maturation process. PMID- 4033602 TI - The role of complement in the pathogenesis of postischemic acute renal failure. AB - One hour occlusion of total renal blood flow results in oliguric acute renal failure as defined by an abrupt and severe diminution in glomerular filtration rate. In rats, after 1-2 h of such ischemia, the acute renal failure which follows is characterized by decreased renal blood flow and by intratubular obstruction with necrotic cellular debris. The present study has examined the possible role of the complement system in the development of this model of acute renal failure. Immunoreactive C3 was extensively localized within necrotic tubular epithelial cells and the walls of small muscular arteries in reperfused kidneys after 1 h of total renal ischemia. Depletion of complement by the administration of cobra venom factor 18 h prior to the induction of ischemia abrogated C3 localization and significantly attenuated the subsequent fall in renal blood flow following reperfusion but did not alter the oliguria or marked fall in glomerular filtration. PMID- 4033603 TI - Microinjection study of renal calcium absorption in the phosphate-depleted rat. AB - Tracer microinjection studies were performed in chronically phosphate-depleted (CPD) and phosphate-supplemented (PS) rats in order to determine the site of the defect in calcium absorption which developed in CPD. Calcium recovery in the final urine was significantly higher in CPD than in PS rats after microinjections into the early and the late proximal tubules. However, there was no significant difference in the urinary recovery between the two groups after injection into the early and late distal convoluted tubules. The difference in calcium recovery in late proximal studies persisted during PTH infusion. This indicates that there is a defect in calcium absorption in phosphate-depleted rats between late proximal and early distal tubules, which is not correctable with PTH infusion. PMID- 4033604 TI - Recurrence after a single renal stone in a community practice. AB - The natural history of recurrence of kidney stones was studied in a community urology practice, in which treatment with agents such as thiazide, allopurinol or oral phosphate has not been consistent or widespread. Using life-table analysis, the mean interval to first recurrence was 8.8 +/- 1.2 years and was not influenced by gender, age at first occurrence, or family history of stones. The tempo of recurrence justifies an individual approach to evaluation and treatment. PMID- 4033605 TI - [Statistical evaluation of neonatal mortality in the 20-year period between 1960 1980]. PMID- 4033606 TI - [Analysis of immunoglobulins and secretory components in the saliva of children, before and after adenotonsillectomy]. PMID- 4033607 TI - [Chronic cor pulmonale caused by hypertrophy of Waldeyer's lymphatic ring in an achondroplasic subject]. PMID- 4033608 TI - [A rare case of temporomandibular joint dysfunction syndrome in childhood]. PMID- 4033609 TI - [A rare case of cavernous hemangioma of the bladder]. PMID- 4033610 TI - [Congenital pulmonary cystic adenomatous malformation with onset in the neonatal period]. PMID- 4033611 TI - [Suspected case of malignant hyperthermia of sporadic onset]. PMID- 4033612 TI - Renal capsular leiomyoma causing painless microscopic hematuria. An unusual manifestation of a rare tumor. PMID- 4033613 TI - Retroperitoneal liposarcoma. PMID- 4033615 TI - Drug therapy for rheumatoid arthritis. PMID- 4033614 TI - Ammoniated mercury membranous nephropathy. PMID- 4033616 TI - Metastatic cancer of unknown primary. PMID- 4033617 TI - Commentary on the Minnesota Medical Association's do-not-resuscitate guidelines. PMID- 4033618 TI - Institutional ethics committee's roles, responsibilities, and benefits for physicians. Committee on Ethics and Medical-legal Affairs. PMID- 4033619 TI - Physicians contemplate the ethics and economics of health care. Report of the MMA Ad Hoc Work Group on "Price of Life" report. PMID- 4033620 TI - MMIE malpractice claim review. Oncology. MMIE Risk Management Committee. PMID- 4033621 TI - [Clinical significance of urinary N-acetyl-beta-D-glucosaminidase activities in surgery]. AB - Urinary N-acetyl-beta-D-glucosaminidase (U-NAG) activities were measured in 62 patients surgically treated in our clinic. The results obtained were as follows: The preoperative U-NAG activities were 9.53 +/- 8.63 IU/day in patients in elective operations, and 31.39 +/- 23.47 IU/day in cases in emergency surgery or exploratory laparotomies. The U-NAG activities were elevated slightly even in patients with no postoperative complications, suggesting there was significant damage to the renal tubular epithelium. In the patients with postoperative complications, the U-NAG activities were elevated markedly, especially in those with circulatory shock, suggesting severe damage to the renal tubular epithelium. Though the U-NAG showed abnormally high activities, the values of BUN, S-Cr, U protein, UUN/BUN, FENa, Ccr, CH2O remained within the normal range. On the contrary, when they were abnormal, the U-NAG activities were not elevated. All patients, who showed high U-NAG activities with abnormal values of Ccr and/or CH2O, developed acute renal failure (ARF). In order to detect ARF in an early stage, Ccr and CH2O should be measured when U-NAG activities rose to over 50 IU/day. PMID- 4033622 TI - [A histopathologic study of the disseminated peritoneal metastasis of gastric cancer]. AB - A total of 117 cases of gastric cancer with peritoneal metastasis was subjected to gross observation and histopathologic examination of metastatic lesion to clarify whether the metastases change in morphology along with time. When the patterns of gross morphology were classified by the time of ascertainment, the disseminated or scattered nodule type occupied 94% in the time of first surgery, which were reduced to 74% in relapse or recurrence. Postmortem examined cases showed very high incidences of the diffuse infiltration type. In 12 cases receiving laparotomy twice, the nodule type was outstanding in the first surgery and in recurrence, while the infiltration type was noted in relapse and at autopsy. These are indicative of chronologic transition of gross appearances of peritoneal metastases along with the development of cancer. Histopathologic observations suggested that when poorly differentiated adenocarcinoma (especially of the scirrhous and intermediate type) was metastasized intraperitoneally, the metastases were of the nodule type first, and then gradually proceeded into the infiltration type. When well differentiated adenocarcinoma or poorly differentiated adenocarcinoma of the medullary type were metastasized, they formed nodular type metastasis, however, poorly differentiated adenocarcinoma of the scirrhous type recognized as the morphologic subtype of carcinoma in the primary lesion proliferated later. These metastases might be infiltrate proliferated superiorly, which have presumably produced time changes in their gross appearance. PMID- 4033623 TI - [The significance of the measurement of a serum gonadotropin-like substance in gastric cancer]. AB - The serum concentration of hCG and CEA in 277 gastric cancers was extensively studied. 8.6% for hCG and 18% for CEA were regarded as positive. 9.4% of patients showed elevated serum level for both hCG and CEA, on the other hand 7% of the patients showed high hCG only. All of hCG positive patients had severe lymph nodal involvement. All cases of hCG positive and 85% of CEA positive cases were classified as stage 4. Macroscopically, 85% of hCG positive cases and 40% of CEA positive cases showed generalized type. Histological type was poorly differentiated adenocarcinoma in 72% of tumors with elevated serum hCG level, but in only 35% of tumors with elevated serum CEA level. The content of hCG subunits in serum and tumor showed different levels among patients. The hCG positive cases did not reveal endocrine symptom. The prognosis of these patients with elevated serum hCG and CEA level were poor. One year survival rates were 0% and 30%, respectively. These results showed that both hCG and CEA, especially when used in combination, was potentially useful marker for determination of staging, recurrence and prognosis in gastric cancer. PMID- 4033624 TI - [Influence of post-vagotomy duodenogastric reflux on gastric mucosal structure]. AB - There has not come to any definite conclusion on morphological changes in post vagotomy gastric mucosa. And, it was reported that duodenogastric reflux in consequence of pyloroplasty or gastroenterostomy could aggravate these gastric mucosal changes. To elucidate this problem, 34 Wistar male rats were subjected to either truncal vagotomy, duodenogastric reflux procedure (transection of the lower part of the duodenum and gastrojejunostomy), or truncal vagotomy with duodenogastric reflux procedure. After 12 weeks, rats were killed for histologic studies of gastric mucosa. Rats subjected to vagotomy with duodenogastric reflux procedure showed marked atrophy of gastric glands, reduction in number of parietal cells and gastrin cells, formation of small ulcer, and generation of heterotopic glands. Rats subjected to duodenogastric reflux also showed chronic ulceration in the prepyloric region on the lesser curvature and hyperplasia of gastric glands. However, no remarkable changes were observed in the stomach of rats with vagotomy. These results indicate that chronic influence of postvagotomy duodenogastric reflux can lead to severe gastritis as well as altered structure of gastric mucosa. PMID- 4033625 TI - [Significance of cross-circulation on obstructive jaundice in rats with special reference to the mitochondrial function of the liver and kidney]. AB - Cross-circulation was performed to investigate the mitochondrial respiratory function of the liver and kidney in rats after 1, 2 and 3 weeks of biliary obstruction. Serum bilirubin and total bile acids concentration in blood in rats with biliary obstruction markedly decreased with 3 hours cross-circulation. There demonstrated, however, no significant change in mitochondrial function in the liver after cross-circulation. In contrast, mitochondrial function in the kidney showed significant improvement after 3 hours cross-circulation. Mitochondrial respiratory function in normal partner rats cross-circulation with jaundiced rats demonstrated temporal deterioration in the kidney and prolonged deterioration in the liver. It can be concluded that cross-circulation or plasma exchange might be useful for the prevention of renal failure in obstructive jaundice, since cross circulation induced persistent improvement of the mitochondrial respiratory function in the kidney deteriorated by biliary obstruction. PMID- 4033626 TI - [Systemic hemodynamics and oxygen metabolism in acute portal vein occlusion and following restoration of portal vein flow in canines]. AB - This study was undertaken in order to clarify the influence of acute portal vein occlusion (PVO) and the following restoration of portal vein flow (R-PVF) in adult mongrel dogs. Acute abnormality was observed on systemic circulation and oxygen metabolism quickly after PVO, causing the shock to dogs. The hypovolemia causing by splanchnic sequestration was the leading cause at the early stage. As the occlusion time was extended, the cardiac function was lowered and the oxygen metabolism was destroyed. Using Anthron bypass catheter between portal and femoral veins during the PVO, the intestinal blood congestion was prevented and the influence on the oxygen metabolism was slight. After R-PVF, the cardiac functional deterioration and deficient compensation of oxygen metabolism were observed, which were more worsened as the occlusion time was longer. The simultaneous occlusion of the portal vein and superior mesenteric artery failed to improve the deterioration of systemic circulation and oxygen metabolism. No improvement of prognosis of dogs was found either. On the contrary, the systemic circulation was improved through the administration of dobutamine during PVO and after R-PVF, the improvement of systemic circulation and oxygen metabolism was also improved and the prognosis of dogs was improved. PMID- 4033627 TI - [The evaluation of the nutritional condition and the absorptive capacity in long term follow-up of infants with short bowel syndrome]. AB - The nutritional conditions and absorptive capacity of nine infants with short bowel syndrome were investigated during a long follow-up period from one and half years to 14 years and 7 months. The length of the residual small intestine ranged between 13 and 90cm. The nine infants had normal meals at home and did not suffer from persistent diarrhea. Most of the infants were thin. Nutritional conditions, for example, serum protein, triglycerides, vitamins, trace elements and plasma amino acids, were kept relatively well, and there were no symptoms of deficiency. The results of D-xylose absorption test had gradually improved but the absorptive capacity of sugars and amino acids observed by potential differences were within the normal limits or slightly subnormal except one infant. This indicated that the absorptive capacity of sugars and amino acids per a given area of the residual small intestine did not increase. From our examination the critical length of intestine might be in the neighborhood of 50cm. The infants left with less than 50cm of small intestine seem to have grown up normally but malabsorption of fat, sugars and bile acids have continued for many years. PMID- 4033628 TI - [Successful surgical management of extracranial high internal carotid aneurysm. A case report]. AB - A 76 year-old woman visited our university hospital with a complaints of dysphagia of 3 months duration and was discovered to have a right internal carotid aneurysm protruding to the right side of the larynx. A day prior to admission, dysarthria and left hemiparesis occurred with sudden onset. These ischemic attacks spontaneously remitted within 48 hours. A carotid arteriogram showed a saccular aneurysm located high in the right internal carotid artery. Four days after admission, aneurysmectomy with end-to-end anastomosis was carried out with the temporary internal shunt under the induced hypertension. There was no sign of ischemic brain damage after the operation. But she suffered from dysphagia due to the NO. 9, 10, and 12 cerebral nerve palsies, which took 5 months to recover completely. Despite several difficulties in the operation for a highly located internal carotid aneurysm, we emphasize in this report the necessity of aneurysmectomy and the establishment of vascular continuity with the aid of internal shunt to prevent the ischemic brain damage. PMID- 4033630 TI - High affinity binding of [3H]acetylcholine to muscarinic receptors. Regional distribution and modulation by guanine nucleotides. AB - The interaction of [3H]acetylcholine ([3H]AcCh) with the muscarinic receptor was studied in seven distinct rat brain regions and in heart atrium by employing 10 microM atropine to define specific binding. The specific binding exhibited by the labeled neurotransmitter was found to be sensitive to muscarinic but not to nicotinic drugs. The muscarinic high affinity agonist-binding sites were characterized with respect to their binding properties, regional distribution, pharmacology, and modulation by guanyl nucleotides and by transition metal ions. In all tissues examined, specific binding of [3H]AcCh was saturable over the range of 4-200 nM and occurred in a receptor population that was apparently homogeneous and had a dissociation constant of approximately 19-39 nM in most of the regions. The ratio of muscarinic receptors labeled by [3H]AcCh to those labeled by the potent antagonist [3H]N-methyl-4-piperidylbenzilate varied markedly among tissues, from 0.15 in the hippocampus to 0.71 in the atrium. This ratio was lower in brain regions rich in muscarinic receptors, where smaller sensitivity of [3H]AcCh binding to guanyl nucleotides was also observed. In the presence of the latter [3H]AcCh binding was decreased by 25 to 90% in different tissues, with the greatest decreases occurring in the atrium and brainstem. In the latter preparations, transition metal ions do not affect [3H] AcCh binding, while in the other preparations studied they induce an increase in the binding capacity for the labeled neurotransmitter, which is sensitive to guanine nucleotides. PMID- 4033629 TI - Isozyme selectivity of the inhibition of rat liver cytochromes P-450 by chloramphenicol in vivo. AB - The isozyme-selectivity of chloramphenicol as an inhibitor of rat liver cytochromes P-450 has been investigated. Untreated rats and rats treated with the inducers phenobarbital, beta-naphthoflavone, pregnenolone 16 alpha-carbonitrile, and clofibrate have been injected intraperitoneally with chloramphenicol, and inhibition of specific cytochrome P-450 isozymes has been assessed by monitoring the metabolism of warfarin, testosterone, isosafrole, or lauric acid in subsequently prepared hepatic microsomal preparations. Of eight major cytochrome P-450 isozymes which could be monitored in this fashion, three were inhibited by more than 50% by a dose of chloramphenicol of 300 mg/kg, whereas no evidence of inhibition of the remaining isozymes was obtained. P-450PB-C, an isozyme which is present in significant amounts in untreated rats and which is induced approximately 2-fold by phenobarbital, was the most susceptible cytochrome P-450 to inhibition by chloramphenicol both in vivo and in vitro. P-450PB-B, the major phenobarbital-inducible isozyme, and P-450UT-A, a male-specific testosterone 2 alpha- and 16 alpha-hydroxylase, were intermediate in their susceptibility to chloramphenicol. In contrast, the major isozymes induced by beta-naphthoflavone, pregnenolone 16 alpha-carbonitrile, and clofibrate, as well as a constitutive testosterone 7 alpha-hydroxylase, were not inhibited by chloramphenicol. PMID- 4033631 TI - Mechanisms of N-acetyl-p-benzoquinone imine cytotoxicity. AB - N-Acetyl-p-benzoquinone imine (NAPQI), a reactive metabolite of acetaminophen, rapidly reacts at physiological pH with glutathione (GSH) forming an acetaminophen-glutathione conjugate and stoichiometric amounts of acetaminophen and glutathione disulfide (GSSG). The same reaction products are formed in isolated hepatocytes incubated with NAPQI. In hepatocytes which have been treated with 1,3-bis-(2-chloroethyl)-1-nitrosourea (BCNU) in order to inhibit glutathione reductase, the initial rise in GSSG concentration in the presence of NAPQI is maintained, whereas GSSG is rapidly reduced back to GSH in untreated hepatocytes. Oxidation by NAPQI of GSH to GSSG and the reduction of GSSG back to GSH by the NADPH-dependent glutathione reductase appear to be responsible for the rapid oxidation of NADPH that occurs in hepatocytes incubated with NAPQI in that the effect is blocked by pretreatment of cells with BCNU. When added to hepatocytes, NAPQI not only reacts with GSH but also causes a loss in protein thiol groups. The loss in protein thiols occurs more rapidly in cells pretreated with BCNU or diethylmaleate. Whereas both of these treatments enhance cytotoxicity caused by NAPQI, BCNU pretreatment has no effect on the covalent binding of [14C-ring]NAPQI to cellular proteins. Furthermore, dithiothreitol added to isolated hepatocytes after maximal covalent binding of [14C-ring]NAPQI but preceding cell death protects cells from cytotoxicity and regenerates protein thiols. Thus, the toxicity of NAPQI to isolated hepatocytes may result primarily from its oxidative effects on cellular proteins. PMID- 4033632 TI - DNA synthesis inhibitory peptides in mammalian serum and insect hemolymph. AB - Similar inhibitory factors for DNA synthesis were found in fetal calf serum and a hemolymph of the moth, Bombyx mori. The factors were highly purified by gel filtration, ion exchange and thin layer chromatography and appeared to be heat stable. They showed the same effects on some bacteria and mammalian cells. The significance of these DNA synthesis inhibitory 1 Kd peptides is discussed. PMID- 4033633 TI - Interaction of histone H1 from sea urchin sperm with superhelical and relaxed DNA. AB - Complexes of histone H1 from sea urchin sperm (H1S) and calf thymus (H1T) with superhelical DNA I and relaxed circular DNA II have been analyzed by analytical sedimentation. Similar to H1T, the highly basic and relatively arginine-rich histone H1S preferentially interacts with DNA I compared to DNA II under competition conditions. However, H1S induces a stronger aggregation of both forms of DNA than H1T. Below 0.05 M NaCl, the soluble complexes formed by both histones have similar properties, but aggregation proceeds in a different manner: H1S induces a stronger aggregation of DNA II as compared to DNA I, whereas H1T fails to aggregate DNA I. The results are explained on the basis of differences in amino acid sequence and structure of the two histones and related to the special chromatin condensing ability of histone H1S. PMID- 4033634 TI - DNA cleavage in chromatin spacer segments by a non-enzymic probe, 1,10 phenanthroline-copper complex. AB - The action of 1,10-phenanthroline-copper complex under aerobic conditions in the presence of 2-mercaptoethanol on chromatin DNA in murine thymocyte nuclei was studied. At limited oxygen supply primarily multiple single-strand breaks of DNA in the spacer segments are observed while the core DNA segments in chromatin remain intact. After the single-strand breaks accumulate in both DNA strands (under conditions of improved oxygen supply), double-strand cleavage of DNA to fragments of nucleosomal size becomes apparent. This regular character of DNA degradation in chromatin is apparently due to the preferential binding of the 1,10-phenanthroline-copper complex to DNA of the spacer segments and to the localized generation of damaging radicals. PMID- 4033635 TI - An increase of the regulating factor for chromatin-dependent RNA polymerase II reactions in the tightly-bound chromatin fraction by glucocorticoid injection. AB - A sugar-containing factor for chromatin-dependent RNA polymerase II reactions exists in rat liver nuclei (1). In this communication the localization of this factor in cell nuclei was investigated. The major activity of the factor was observed in the nuclear soluble fraction whereas a minor activity was detected in the tightly-bound chromatin fraction, but not in the loosely bound chromatin fraction. The factor in the tightly-bound chromatin fraction was considerably increased by glucocorticoid injection, but not in other fractions. PMID- 4033636 TI - Hypomethylation of repair patches in HeLa cells. AB - In HeLa cells, under conditions where normal semiconservative synthesis is suppressed by hydroxyurea, the excision repair process after irradiation by UV results in a small amount of incorporation of nucleotides into nonreplicated DNA. By labelling the cytosine moieties of these repair patches, and measuring the ratio between cytosine and 5-methylcytosine, we have found that the level of methylation of cytosine in repair patches five hours after UV-irradiation of the cells is about half of that observed in normal semiconservatively synthesized DNA. PMID- 4033638 TI - [Characteristics of nuclear DNA of a Lepidoptera, the great wax moth Galleria mellonella, using reassociation kinetics]. AB - Reassociation kinetics of great wax moth--Galleria mellonella nuclear DNA short fragments was studied within the C0t values of 0.02 and 10(4). The least squares analysis of the experimental curve obtained revealed two components with C0t1/2 = 0.72 and C0t1/2 = 750 appropriately. The fraction of the component with C0t1/2 = 0.72 in the genome of great wax moth is 22% and that of the other one is 61%. There is also a rapid component which renatured at the C0t values less then 0,02. The fraction of this component in the genome is 17%. The great wax moth genome size determined kinetically is 4,83 X 10(8) base pairs. It was shown that the efficiency of DNA molecules network formation can qualify the genome studied as being a short or a long period of interspersion. On the basis that 80-90% of great wax moth DNA molecules participated in network formation which is inherent to the short period interspersion genomes, it was concluded that the great wax moth genome is of the Xenopus-like type. PMID- 4033637 TI - [Thermal denaturation of DNA in concentrated salt-free solutions: comparison of microcalorimetric and spectrophotometric data]. AB - Scanning microcalorimetry and spectrophotometry were used to study the dependence of melting enthalpy (delta Hm) and temperature (Tm) on DNA concentration in salt free solutions and on NaCl concentration in solutions with constant DNA concentration. This data is used to calculate the Manning's charge density parameter which is found to be equal 1.8. The linear dependence of Tm on the logarithm of DNA concentration in salt free solution was obtained. An approximate evaluation of dissociation degree in native DNA at different concentrations was made by comparison of straight lines in the Tm = f(lg CNaCl) and Tm = f(lg Cp) coordinates. PMID- 4033639 TI - [Synthesis of the tobacco mosaic virus in blocked spreading of infection]. AB - The possibility of infection of tobacco upper leaves with tobacco mosaic virus (TMV) was examined in experiments where the inoculum was imbibed through the cut stem. The inoculum used were: a) a preparation of a virus-specific informosome like ribonucleoproteins (vRNP) isolated from TMV-infected plants; b) a TMV preparation; or c) a mixture of TMV and vRNP. Multiplication of TMV in upper leaves was observed in neither of the variants; nevertheless in the vascular tissue and/or probably in adjoining parenchymal cells, two kinds of RNA were synthesized: of mol. w. (1.1--1.3) X 10(6) and (0.6--0.8) X 10(6). These RNA were not found in healthy plants in the presence of actinomycin D. The synthesis of genomic TMV RNA is suppressed under these conditions. Thus, some kind of abortive TMV infection takes place under the condition of experimental inoculation of plants through a cut stem. Molecular hybridization with the DNA of recombinant plasmid containing a nucleotide sequence complementary to the 3'-portion of genomic TMV RNA proves that short RNAs synthesized under the abortive infection conditions are TMV-specific. The experiments with differential temperature treatment of N-gene-containing plants under abortive infection conditions suggest that necrotization is not necessarily induced by genomic TMV RNA synthesis. PMID- 4033640 TI - [Effect of monovalent cations on the catalytic and spectral properties of tyrosine-phenol-lyase from Citrobacter intermedius]. AB - The action of monovalent cations Li+, Na+, K+, Rb+, Cs+, NH4+ on catalytic and physico-chemical properties of bacterial tyrosine--phenol-lyase was investigated. It was shown that K+, Rb+, Cs+, NH4+ were the noncompetitive activators of the enzyme, Na+ was an inhibitor, Li+ did not influence the catalytic activity. The values of KA and Vmax were determined for the activators in the reaction of alpha, beta-elimination of L-tyrosine. Monovalent cations affect the absorption and CD spectra of the enzyme and its complex with the quasi-substrate--L-alanine. It was suggested that an activation of tyrosine phenollyase by monovalent cations was connected with the increase of the active protonated form of the holoenzyme (lambda max 420 mm) induced by the cations-activators. PMID- 4033641 TI - [Formation of noncanonical structures in superhelical DNA. Mutual effects of various transitions]. AB - This is a theoretical study of the problem of formation of noncanonical structures, cruciforms in palindromic regions and the Z form in purine- pyrimidine sequences, in negatively supercoiled DNA. If two such regions, one palindromic and one purine--pyrimidine, are present in the same DNA molecule of a finite length, then transitions between the regular B form and noncanonical structures in these regions will experience a considerable mutual influence. This takes place because both noncanonical structures compete for the same superhelix energy. A special attention is paid to the case when the probability of the Z form formation nonmonotonously depends on the superhelix density. Such a situation is shown to be possible for some specific interrelation between the DNA length, the length of the palindromic region and the length of the purine- pyrimidine region. The calculations show that in this case the Z form is formed first with the increasing superhelix density, that the cruciform structure is formed whereas the purine--pyrimidine region returns into the B form, and finally, the Z form is formed again. The possibility of experimental observation of such unusual behaviour is discussed. PMID- 4033642 TI - [Interaction of formaldehyde with nucleic acids and their structural components in the presence of amines. II. Structure of adenine derivatives formed in the reaction with formaldehyde and primary amine]. AB - Two products of modified adenine have been isolated from reaction of adenine with a mixture of formaldehyde and methylamine; their structures have been demonstrated by UV, 1H NMR and mass spectra data. The formal scheme of reaction can be described as simultaneous or sequential cycloaddition of dimethylol derivatives of methylamine to two reaction's positions of the adenine residue. This results in the formation of a new partly or completely hydrogenated six membered 1,3,5-triazine cycle which has the atoms of adenine nitrogen in its 1,3 positions and nitrogen of methylamine in 5-position. This is used as a model for discussing the peculiarities of DNA-formaldehyde interaction in the presence of amine. PMID- 4033643 TI - [Structural characteristics and availability of DNA for solvent molecules in nuclei of Physarum polycephalum]. AB - The rate constants of 1H--3H exchange between water and C8H-groups of purinic residues of DNA in solution and in nuclei of synchronous Physarum polycephalum at different phases of the cell cycle were measured. The nuclear membranes and nonhistone proteins were shown not to create additional hindrances and not to diminish the availability of DNA in nuclei for solvent molecules. A small increase of the rate of the 1H--3H exchange between water and the DNA of nuclei upon transition from the S-phase to the late G2-phase seems to reflect the process of chromatin decondensation connected with activation of the transcription and local changes of the secondary structure of DNA at the late G2 phase of the cell cycle. PMID- 4033644 TI - [Conformation of glycopeptides with L- and D-stereoisomers of Ala and Glu amino acids]. AB - On the base of the semi-empirical method of conformational analysis low-energetic conformations have been found for the glycopeptides with the O-beta-N-acetyl-D muramic acid or the O-beta-N-acetyl--D-glucosaminyl-(1-4)-N-acetyl-D-muramic acid in the glycan part and L-Ala--D-GluNH2, L-Ala--L-GluNH2, D-Ala--D-GluNH2 in the peptide part. It was shown that for either molecule preferentiability of any conformation is determined mainly by interactions between dipeptide and muramic acid residue. PMID- 4033645 TI - [The theory of ligand migration in biomacromolecules]. AB - A model for the process of ligand migration in bio-macromolecules is proposed. We assume that migration occurs by means of fluctuating creation of cavities in bio macromolecules. A theory of particle migration through the fluctuating gap is created. The rate of migration is determined analytically for limiting cases. Theoretical results are applied to the migration of CO in myoglobin. PMID- 4033646 TI - [The role of H2B histones from the sea urchin sperm in the formation of supranucleosome structures]. AB - The structural role of histone H2B from sea urchin sperm (H2Bsp) has been examined in experiments on reconstitution of chromatin from DNA and core histones taken in three variants: (1) four core histones from sea urchin sperm; (2) four core histones from calf thymus; (3) (H3, H4, H2A) from calf thymus and H2Bsp. It is shown that H2Bsp when present in reconstituted chromatin induces its aggregation. Fidelity of the reconstitution of nucleosomes has been tested using DNase I probe, one- and two-dimensional electrophoresis and electron microscopy. The reconstitutes that contain H2Bsp appear under electron microscope mainly as regular closely spaced large granules, about 450 A in diameter, which are very similar to the granules found in "native" sea urchin sperm chromatin. The reconstitutes formed by four core histones from calf thymus appear as randomly arranged particles, about 100 A in diameter. We conclude that histone H2Bsp participates in interactions between nucleosomes and is involved in the formation of the condensed supranucleosomal structure in sea urchin sperm chromatin. PMID- 4033647 TI - [Study of specific interactions of amino acid esters with the synthetic polynucleotides poly(A) x 2 poly(U), poly(A) x poly(U) and poly(A) by thermal denaturation]. AB - The interactions of amino acid esters with poly(A)x2poly(U) and poly(A)xpoly(U) have been investigated by means of thermal denaturation of these polynucleotides. The esters under consideration raised the melting point, revealing the preferable binding to helical polynucleotide structures. The melting point shifts demonstrate the following sequence of the stabilities of these complexes: Arg greater than Lys much greater than His greater than Met greater than Ser greater than Gly. The same stability order is observed when studying the polynucleotide renaturation in the presence of esters. This order coincides with that previously obtained for the nucleotide base--amino acid ester complexes excepting basic amino acid esters. The ester interactions with poly(A) and poly(U) also reveal the specificity of monomer--monomer interactions. Some dynamic contributions into the studied specificity are also discussed. PMID- 4033648 TI - [The effect of the medium on the functional and structural properties of serum albumins. III. Relation between the N-F1-, F1-F2- and F2-E transitions of human serum albumin and temperature and ionic strength]. AB - Using fluorescence parameters of tryptophanyl and bound ANS, the acid-induced structural transitions of defatted monomeric human serum albumin were measured as pH-dependences from 6 to 2.5 in the wide range of temperature (10 to 45 degrees C) and ionic strength (from 0.001 to 0.2 M NaCl or 0.067 M Na2SO4). Temperature rise and decrease in ionic strength value result in the splitting of the N-F transition onto two stages, N-F1 and F1-F2. The N-F1-transition is accompanied by the blue shift of tryptophanyl and ANS fluorescence spectra and increase in the ANS emission yield. The F1-F2-stage is manifested in an additional blue spectral shift and a sharp drop of the ANS emission yield, which is shown to be due to the lowering of albumin affinity for the dye. In the acidic-extension stage (F2-E), the spectra undergo a red shift which means that the nanosecond dipole relaxation of protein groups and bound water becomes faster. In the F2 from, the albumin affinity for ANS is significantly lowered; the association constant of the primary binding site is lower by an order of quantity and two secondary sites are practically disappeared. The complex effect of temperature, ionic strength and pH changes on the properties of ANS-binding sites is considered as a model of possible control influences of these factors upon the albumin transport of amphiphilic anions in organism. PMID- 4033649 TI - Specific regions of beta-globin RNA are resistant to nuclease digestion in RNA protein complexes in chicken reticulocyte nuclei. AB - The interaction between beta-globin RNA and proteins in chicken reticulocyte nuclei was studied by determining the sequence of nuclease-resistant beta-globin RNA. Two types of nuclease-resistant RNAs were isolated for this study: endogenous nuclease-resistant RNA from 50S heterogeneous nuclear RNA-protein complexes and micrococcal nuclease-resistant nuclear RNA from whole nuclei. The nuclease-resistant regions were identified with the use of a RNA mapping method we recently developed (J.R. Patton and C.-B. Chae, J. Biol. Chem. 258:3991-3995, 1983). We found that beta-globin RNA is assembled into heterogeneous nuclear RNA protein complexes in a specific manner. There are several regions of nuclease resistance in the first and third exons interrupted at regular intervals by sensitive regions. The second exon has only one nuclease-resistant region. The resistant regions range in size from 20 to 50 nucleotides. This organization may reflect a specific mode of assembly for heterogeneous nuclear RNA-protein complexes. PMID- 4033650 TI - Rapid purification of mammalian 70,000-dalton stress proteins: affinity of the proteins for nucleotides. AB - A new and rapid purification procedure has been developed for the mammalian 70,000-dalton (70-kDa) heat-shock (or stress) proteins. Both the constitutive 73 kDa protein and the stress-induced 72-kDa protein have been purified by a two step procedure employing DE52 ion-exchange chromatography followed by affinity chromatography on ATP-agarose. The two proteins, present in approximately equal amounts in either the 12,000 X g supernatant or pellet of hypotonically lysed heat-shock-treated HeLa cells, were found to copurify in relatively homogenous form. The purified proteins were covalently labeled with the fluorescent dye tetramethylrhodamine isothiocyanate, and the fluorescently labeled proteins were introduced back into living rat embryo fibroblasts via microinjection. The microinjected cells maintained at 37 degrees C showed only diffuse nuclear and cytoplasmic fluorescence. After heat-shock treatment of the cells, fluorescence was observed throughout the nucleus and more prominently within the nucleolus. This result is consistent with our earlier indirect immunofluorescence studies which showed a nuclear and nucleolar distribution of the endogenous 72-kDa stress protein in heat-shock-treated mammalian cells. The result also indicates that, for at least the 72-kDa protein, (i) the protein has been purified in apparently "native" form and (ii) its nucleolar distribution is stress dependent. PMID- 4033651 TI - Gene amplification in Tetrahymena thermophila: formation of extrachromosomal palindromic genes coding for rRNA. AB - Tetrahymena thermophila contains in the macronucleus multiple copies of extrachromosomal palindromic genes coding for rRNA (rDNA) which are generated from a single chromosomal copy during development. In this study we isolated the chromosomal copy of rDNA and determined the structure and developmental fate of the sequence surrounding its 5' junction. The result indicates that specific chromosomal breakage occurs at or near the 5' junction of rDNA during development. The breakage event is associated with DNA elimination and telomeric sequence addition. Similar results were also found previously for the 3' junction of this gene. These results could explain how the extrachromosomal rDNA is first generated. Near both junctions of the chromosomal rDNA, a pair of 20-nucleotide repeats was found. These sequences might serve as signals for site-specific breakage. In addition, we found a pair of perfect inverted repeats at the 5' junction of this gene. The repeats are 42 nucleotides long and are separated by 28 nucleotides. The existence of this structure provides a simple explanation for the formation of the palindromic rDNA. PMID- 4033652 TI - Locus encoding a family of small heat shock genes in Caenorhabditis elegans: two genes duplicated to form a 3.8-kilobase inverted repeat. AB - The genes coding for hsp 16-48, previously identified by cDNA cloning, and for another 16-kilodalton heat shock protein designated hsp16-1 were characterized by DNA sequencing. The two genes were arranged in a head-to-head orientation. Both the coding and flanking regions were located within a 1.9-kilobase module which was duplicated exactly to form a 3.8-kilobase inverted repeat structure. The inverted repeat structure ended in an unusual guanine-plus-cytosine-rich sequence 24 nucleotides in length. The identity of the two modules at the nucleotide sequence level implies that the duplication event may have occurred recently. Alternatively, gene conversion between the two modules could also maintain homology of the two gene pairs. The small heat shock genes of Caenorhabditis elegans contained TATA boxes and heat-inducible promoters, the latter agreeing closely with the Drosophila melanogaster consensus sequence described by Pelham (Cell 30:517-528, 1982). Unlike the homologous D. melanogaster genes, each of these C. elegans genes contained a short intron, the position of which has been conserved in a related murine alpha-crystallin gene. The intron separated variable and conserved regions within the amino acid sequences of the encoded heat shock polypeptides. PMID- 4033653 TI - Interrelationships of protein and DNA syntheses during replication of mammalian cells. AB - During the replication of chromatin, the syntheses of the histone protein and DNA components are closely coordinated but not totally linked. The interrelationships of total protein synthesis, histone protein synthesis, DNA synthesis, and mRNA levels have been investigated in Chinese hamster ovary cells subjected to several different types of inhibitors in several different temporal combinations. The results from these studies and results reported elsewhere can be brought together into a consistent framework which combines the idea of autoregulation of histone biosynthesis as originally proposed by W. B. Butler and G. C. Mueller (Biochim. Biophys. Acta 294:481-496, 1973] with the presence of basal histone synthesis and the effects of protein synthesis on DNA synthesis. The proposed framework obviates the difficulties of Butler and Mueller's model and may have wider application in understanding the control of cell growth. PMID- 4033654 TI - Localization of specific rDNA spacer sequences to the mouse L-cell nucleolar matrix. AB - Mouse L-cell nucleoli were isolated from sonicated nuclei by centrifugation and extensively treated with pancreatic DNase or micrococcal nuclease to obtain "core nucleoli." Core nucleoli still contained the precursors to rRNA and about 1% of the total nuclear DNA, which remained tightly bound even after the removal of some chromatin proteins with 2 M NaCl. The core nucleolar DNA electrophoresed in a series of discrete bands, 20 to about 200 base pairs in length. Hybridization tests with specific DNA probes showed that the DNA was devoid of sequences complementary to mouse satellite, mouse Alu-like, and 5S RNA sequences. It also lacked sequences coding for cytoplasmic rRNA species, since it did not hybridize to the 18S to 28S portion of rDNA in Northern blot analyses and none of it was protected by hybridization to a 100-fold excess of total cytoplasmic RNA in S1 nuclease assays. However, the core nucleolar DNA did hybridize to nontranscribed and external transcribed spacer rDNA sequences. We infer that specific portions of rDNA are protected from DNase action by a tight association with nucleolar structural proteins. PMID- 4033655 TI - Stable transfer and restricted expression of a cloned class I gene encoding a secreted transplantation-like antigen. AB - The identification of a unique major histocompatibility complex class I gene, designated Q10, which encodes a secreted rather than a cell surface antigen has led to questions regarding its potential role in regulating immunological functions. Since the Q10 gene is specifically activated only in the liver, we sought to define the molecular mechanisms which control its expression in a tissue-specific fashion. Results obtained by transfection of the cloned Q10 gene, either in the absence or presence of a heterologous transcriptional enhancer, into a variety of cell types of different tissue derivations are consistent with the Q10 gene being regulated at two levels. The first is by a cis-dependent mechanism which appears to involve site-specific DNA methylation. The second is by a trans-acting mechanism which would include the possibility of an enhancer binding factor. The ability to efficiently express the Q10 gene in certain transfected cell lines offers an opportunity to obtain this secreted class I antigen in quantities sufficient for functional studies; this should also make it possible to define regulatory sequences which may be responsible for the tissue specific expression of Q10. PMID- 4033656 TI - Structure of a murine alpha interferon pseudogene with a repetitive R-type sequence in the 3' flanking region. AB - A murine alpha interferon pseudogene was identified in a mouse genomic library. The nucleotide sequence revealed several in-phase termination codons within the gene and repetitive oligonucleotides in the flanking regions. The nucleotide sequences and the amino acids of the peptide signal sequences were compared with known human alpha interferon genes and the pseudogene. PMID- 4033657 TI - Mutant strain of Chinese hamster ovary cells with no detectable ornithine decarboxylase activity. AB - We previously described an arginase-deficient, polyamine-dependent Chinese hamster ovary cell line which grows in serum-free medium. From this strain we isolated a new mutant strain that has no detectable catalytic ornithine decarboxylase activity. The mutant cells contain, however, immunoreactive ornithine decarboxylase-like protein roughly in the same quantity as the parent strain. The mutant and the parent cell line strains also contain similar amounts of ornithine decarboxylase-mRNA hybridizable to a specific cDNA. If polyamines are omitted from the medium, proliferation of the mutant cells is considerably retarded and ceases in 6 to 10 days. Addition of ornithine or alpha difluoromethylornithine, a specific inhibitor of ornithine decarboxylase, has no effect on these cells. Putrescine and spermidine decreased in the mutant cells to undetectable levels during polyamine starvation, whereas spermine was reduced to 1/5th of that found in the control cultures. Polyamines appear to be indispensable for the mutant strain, but this was obvious only after the amount of polyamines, found as impurities in bovine serum albumin used in the medium, was reduced by dialysis to 10(-12) M. Because sera contain polyamines, the ability of the mutant strain to grow in serum-free medium is a great advantage in elucidation of the mechanisms of polyamine function. PMID- 4033658 TI - Structural and evolutionary relationships among five members of the human gamma crystallin gene family. AB - We have characterized five human gamma-crystallin genes isolated from a genomic phage library. DNA sequencing of four of the genes revealed that two of them predict polypeptides of 174 residues showing 71% homology in their amino acid sequence; the other two correspond to closely related pseudogenes which contain the same in-frame termination codon at identical positions in the coding sequence. Two of the genes and one of the pseudogenes are oriented in a head-to tail fashion clustered within 22.5 kilobases. All three contain a TATA box 60 to 80 base pairs upstream of the initiation codon and a highly conserved segment of 44 base pairs in length immediately preceding the TATA box. The two genes and the two pseudogenes are similar in structure: each contains a small 5' exon encoding three amino acids followed by two larger exons that correspond exactly to the two similar structural domains of the polypeptide. The first intron varies from 100 to 110 base pairs, and the second intron ranges from 1 to several kilobases, rendering an overall gene size of 1.7 to 4.5 kilobases. At least one of the two pseudogenes appears to have been functional before inactivation, suggesting that their identical mutation was generated by gene conversion. PMID- 4033659 TI - Collagen expression in embryonic chicken chondrocytes treated with phorbol myristate acetate. AB - Growth of embryonic chicken sternal chondrocytes in the presence of phorbol-12 myristate-13-acetate (PMA), a potent tumor promoter, resulted in a dramatic morphological change from spherical floating cells to adherent fibroblastic cells. This morphological change was accompanied by a quantitative switch from synthesis of cartilage-specific type II procollagen to type I procollagen. Type II procollagen mRNA levels decreased 10-fold in PMA-treated cells. Activation of type I collagen genes led to the accumulation of type I procollagen mRNA levels comparable to those of type II mRNA in these cells. However, only type I procollagen mRNA was translated. In addition to gene activation, unprocessed pro alpha 1(I) transcripts present at low levels in control chondrocytes were processed to mature mRNA species. Redifferentiation of PMA-treated chondrocytes was possible if cells were removed from PMA after the morphological change and cessation of type II procollagen synthesis but before detectable amounts of type I procollagen were synthesized. Production of type I collagen thus marks a late phase of chondrocyte "dedifferentiation" from which reversion is no longer possible. Redifferentiated cell populations contained 24-fold more pro alpha 1(II) collagen mRNA than pro alpha 1(I) collagen mRNA, but the rates of procollagen synthesis were comparable. This suggests that the PMA-mediated dedifferentiation of chondrocytes as well as their redifferentiation is under both transcriptional and posttranscriptional regulation. PMID- 4033661 TI - Structure of the Dictyostelium discoideum prestalk D11 gene and protein. AB - The gene encoding the prestalk D11 mRNA of Dictyostelium discoideum has been isolated and characterized. Transcriptional mapping and sequence data indicated that the D11 message is unspliced and contains an 846-base open reading frame. The 273 base pairs upstream from the translation initiator codon are 88% A + T, typical of Dictyostelium upstream sequences, and contain no recognizable upstream activator sequence. The deduced D11 protein is exceptionally rich in cysteine residues and consists of a 25-amino acid hydrophobic leader sequence (L) followed by a series of repeats with the structure LA1B1A2B2C1B3C2B4C3B5C4B6, where A, B, and C, are, respectively, amino acid sequences of 39, 18, and 15 residues. The deduced D11 protein shares certain similarities with the Dictyostelium cyclic AMP phosphodiesterase inhibitor protein. PMID- 4033660 TI - Altered beta-actin gene expression in phorbol myristate acetate-treated chondrocytes and fibroblasts. AB - Phorbol-12-myristate-13-acetate (PMA), a potent tumor promoter, was shown to have opposite effects on the cellular morphology and steady-state levels of beta-actin mRNA in embryonic chicken muscle fibroblasts and sternal chondrocytes. When fibroblasts were treated with PMA, they formed foci of densely packed cells, ceased to adhere to culture plates, and had significantly reduced levels of beta actin mRNA and protein. Conversely, when treated with PMA, floating chondrocytes attached to culture dishes, spread out, and began to accumulate high levels of beta-actin mRNA and proteins. In the sternal chondrocytes the stimulation of the beta-actin mRNA production was accompanied by increased steady-state levels of fibronectin mRNAs and protein. These alterations were concomitant with a fivefold reduction in type II collagen mRNA and a cessation in its protein production. After fibronectin and actin mRNAs and proteins reached their maximal levels, type I collagen mRNA and protein synthesis were turned on. Removal of PMA resulted in reduced beta-actin mRNA levels in chondrocytes and in a further alteration in the cell morphology. These observed correlations between changes in cell adhesion and morphology and beta-actin expression suggest that the effect of PMA on cell shape and adhesion may result in changes in the microfilament organization of the cytoskeleton which ultimately lead to changes in the extracellular matrix produced by the cells. PMID- 4033662 TI - Rabbit-mouse hybridomas secreting intact rabbit immunoglobulin. AB - Rabbit-mouse hybridomas offer the potential for production of monoclonal rabbit antibodies by immortal cell lines. In previous studies, it was possible to produce and stabilize rabbit-mouse hybrid cells secreting either a rabbit heavy or light chain. These have been useful for structural characterization of the individual rabbit immunoglobulin polypeptides and for isolation of large amounts of immunoglobulin mRNA for molecular studies. For some studies, however, it would be useful to have intact rabbit immunoglobulin molecules comparable to the myeloma proteins available in the human and mouse. The availability of rapid, sensitive and specific assays for rabbit heavy and light chains and allotypes located on specific chains has now permitted the early identification of clones secreting intact rabbit immunoglobulin. Vigorous cloning efforts have resulted in isolation and partial stabilization of three such clones. The first, H105, secretes a product with a kappa light chain bearing the b6 allotype and a mu chain bearing the a1 allotype. Biochemical and serologic analyses of the product show that it is secreted as a fully assembled IgM pentamer and that the rabbit heavy and light chains are covalently associated. No rabbit J-chain gene was detected in H105 by Southern blot analysis. The second hydridoma, H134, secretes a product with a mol. wt of 150 K, consisting of a b4 light chain and an a1 heavy chain. The third, H171, secretes an alb4 IgG with antibody specificity for group C streptococcal carbohydrate. An additional rabbit-mouse hybridoma, H89, have been produced which secretes a rabbit heavy chain lacking group a allotypic activity. The rabbit heavy chain, which is associated with a mouse light chain, has an N-terminal amino acid sequence identical to a2-positive molecules although thorough serologic analysis revealed no group a allotypic activity. PMID- 4033663 TI - Hyaluronic acid-complement interactions--I. Reversible heat-induced anticomplementary activity. AB - The in vitro interaction of hyaluronic acid (HA) with complement (C) classical pathway activity has been investigated. It was found that native HA, even at a high concn (greater than 3 mg/ml), has a relatively weak anticomplementary activity. However, we report here that native HA can be reversibly altered by heat treatment such that C-inhibitory properties are manifested. We have determined in this study that a potent C-inhibitory activity can be obtained if HA solutions are thermally treated (100 degrees C), and stabilized by prompt freezing with prompt thawing just prior to the interaction with human serum complement. Several investigators have proposed that the intermolecular associated strands of HA undergo a reversible decoupling upon thermal treatment and this decoupled state of HA can be semi-stabilized by quickly cooling the sample. This heat-treated HA strongly inhibits C1 as well as classical-pathway mediated C3 conversion. However, if heat-treated HA samples are not stabilized but, rather, slowly cooled after heating or if heated HA samples are snapfrozen and then slowly thawed, the anticomplementary activity is gradually lost. Interestingly, the activity for this same sample can be regenerated by retreatment of the same sample with heat followed by low-temp stabilization, indicating the reversibility of the physical state of HA responsible for the anticomplementary effect. Since no detectable molecular degradation of thermally treated HA was found, it was assumed that a heat-induced physical transition of HA (decoupled state) was responsible for the C-inhibitory effect. PMID- 4033664 TI - Antigen-binding molecules of T-cells charge heterogeneity and structural lability. AB - T-cell products released by immune cells during culture and which bind specifically the nominal antigens, trinitrophenol (TNP) or oxazalone, were isolated from culture media by hapten-affinity chromatography and compared by isoelectric focusing and 2D-gel analysis. These proteins and an azobenzenearsonate-specific T-cell product synthesized in vitro by translation of mRNA from an azobenzenearsonate-specific T-cell hybrid were also compared for structural lability of the polypeptides. Polyclonal T-cell antigen-binding molecules (TABM) specific for TNP or oxazalone showed marked charge heterogeneity and distinctions in isoelectric focusing in an acidic pH gradient, while the azobenzenearsonate-specific, clonal T-cell product displayed restricted focusing. All TABM studied showed dissociation of Mr 70,000 polypeptides to Mr 45,000 and 25,000 polypeptides after treatment with guanidine. The results provide further evidence for distinctions and similarities between TABM. PMID- 4033665 TI - Effector functions of a monoclonal aglycosylated mouse IgG2a: binding and activation of complement component C1 and interaction with human monocyte Fc receptor. AB - Aglycosylated monoclonal anti-DNP mouse IgG2a produced in the presence of tunicamycin was compared with the native monoclonal IgG2a with respect to its ability to interact with the first component of complement, C1, and to compete with human IgG for binding to human monocyte Fc receptors. The aglycosylated IgG2a was found to bind subcomponent C1q with an equivalent capacity to the native IgG2a, but the dissociation constant was found to be increased three-fold. When activation of C1 by the glycosylated and aglycosylated IgG2a was compared, the rate of C1 activation by the aglycosylated IgG2a was reduced approximately three-fold. In contrast aglycosylation was accompanied by a large decrease (greater than or equal to 50-fold) in the apparent binding constant of monomeric IgG2a to human monocytes. The data suggest that the aglycosylated IgG2a has a structure which differs in the CH2 domain from the native IgG2a, and that the heterogeneous N-linked oligosaccharides of this monoclonal IgG2a which occur at a conserved position in the CH2 domain play a role in maintaining the integrity of its monocyte-binding site. This lack of monocyte binding may result either from a localized conformational change occurring in a single CH2 domain or from an alteration in the CH2-CH2 cross-domain architecture which is normally structured by a pair of opposing and interacting oligosaccharides. The minimal changes in C1q binding and C1 activation suggest that the oligosaccharides are, at most, indirectly involved in these events. PMID- 4033666 TI - Amino acid sequence studies of human C4b-binding protein: N-terminal sequence analysis and alignment of the fragments produced by limited proteolysis with chymotrypsin and the peptides produced by cyanogen bromide treatment. AB - Treatment of human C4b-binding protein (C4BP) with cyanogen bromide gave five major peptides and limited proteolysis with chymotrypsin yielded two fragments. The yields, apparent mol. wts and N-terminal amino acid sequences of these peptides and fragments indicates that in dissociating conditions, after reduction of disulphide bonds, C4BP is composed of only one type of polypeptide chain of approx. 70,000 mol. wt. The amino acid sequence data obtained, which accounts for over 55% of the total sequence, allows an alignment of the cyanogen bromide peptides. In addition the amino acid sequence data indicates that the 70,000 dalton polypeptide chain of C4BP contains nine internal homology regions, each 60 amino acids long, which would account for 540 of the expected 600 amino acids in C4BP. Similar internal homology regions are found within the Ba region of factor B [Morley and Campbell, EMBO J. 3, 153-157 (1984)] and it is of interest that the regions found in C4BP are homologous to those found in Ba. PMID- 4033667 TI - Binding and structural diversity among high-affinity monoclonal anti-digoxin antibodies. AB - High-affinity monoclonal antibodies specific for the cardiac glycoside digoxin provide a useful system for the study of structure-function relationships between antibody combining site and specific antigenic determinants. Fifteen high affinity monoclonal anti-digoxin antibodies were produced when spleen cells from A/J mice immunized with digoxin coupled to human serum albumin (Dig-HSA) were fused with the non-secreting murine myeloma Sp2/0 cell line. Each subcloned hybridoma antibody was analyzed for affinity and specificity for structurally related cardiac glycosides by a radioimmunoassay based on the adsorption of free [3H]digoxin to dextran-coated charcoal. All of the anti-digoxin hybridoma proteins demonstrated high affinity constants ranging from 10(9) to 10(12) M-1. Using seven different analogs of digoxin, binding specificities of the monoclonal antibodies were assessed by inhibition radioimmunoassay. The 15 hybridomas produced from fusions involving five mice could be divided into eight sets on the basis of these binding specificities. Certain antibodies exhibit a preference for the aglycone portion of digoxin, while others are more specific for the tridigitoxose sugar moiety of digoxin. Monoclonal antibody H- and L-chains were subjected to N-terminal amino acid sequence analysis. The antibodies may be divided into several sequence homology sets for both H- and L-chains. In most instances, homologous heavy chains are associated with a set of homologous light chains. Homologous partial sequences, however, do not correlate with similar antigenic specificities and affinities for digoxin. Thus the fine specificity for antigen is not dependent on VH- and VL-encoded sequences alone. These data illustrate the broad diversity of the elicited response to a single hapten, even in inbred mice. PMID- 4033668 TI - Residual complement activity after incubation with myelin isolated from both the central and peripheral nervous tissues. AB - The relative ability of isolated central and peripheral nervous system myelin to interact with the complement system of plasma proteins was studied. The myelin used was a highly pure form, devoid of contamination by any subcellular organelles or membranes. Residual complement activity was a linear function of increasing quantities of myelin from 10 to 40 micrograms of myelin protein. Central and peripheral nervous system myelin showed identical residual complement activity at various temperatures above 7 degrees C and also after various time periods of incubation. The results show that central and peripheral nervous system myelin show equal ability to interact with complement, in spite of their different origin and differences in morphology and protein composition. PMID- 4033669 TI - Macrophage-produced muramyl peptide contaminants as adjuvants in cell-transfer experiments. PMID- 4033670 TI - Preparation and biologic characterization of fragments containing dimeric and monomeric C gamma 2 domain of rabbit IgG. AB - A number of fragments derived from acid-treated rabbit IgG by digestion with plasmin have been separated by high-resolution gel filtration. Fragments isolated included a dimer and monomer Facb, named F(acb)2 and Facb, respectively and a heterodimer composed of Facb and Fab subunits, named F(acb)(ab). A C gamma 2 fragment was obtained by papain digestion of Facb. A heterodimer composed of Facb and Fab', named F(acb)(ab'), was also prepared by oxidizing a reduced mixture of these fragments. Fragments thus obtained are classified into two groups--those carrying paired C gamma 2 domains, i.e. F(acb)2, and the disulfide-linked dimeric C gamma 2 fragment; and those having a single C gamma 2 domain, i.e. reduced, alkylated Facb and C gamma 2 fragment, F(acb)(ab) and F(acb)(ab'). These fragments exhibited marked differences in their capacity to activate complement in assay systems of hemolysis and complement consumption by immune complexes or aggregates on polystyrene latex. Fragments of the former group could activate complement but with a definitely reduced efficiency (50%) compared to intact IgG, whereas fragments of the latter group were practically inactive. Although it was not determined whether the C1-binding capacity itself is changed by monomerization of the C gamma 2 domain, the results suggested that the intact paired C gamma 2 module is required at least for the activation process of complement. PMID- 4033671 TI - Human natural killer cytotoxic factor. Studies on its production, specificity, and mechanism of interaction with target cells. AB - Human peripheral blood lymphocytes cultured in vitro for 2 days in serum-free conditions produced a natural killer (NK) cytotoxic factor (NKCF) which selectively killed NK-susceptible targets. Optimal release of NKCF was achieved under serum-free conditions, while the presence of fetal calf serum inhibited both the production and activity of the factor. Mechanistic studies with NKCF demonstrated that the factor could be adsorbed by the target cells within 6 h, with no further exposure to NKCF required for maximal levels of lysis of the treated targets after additional 30-48 h of incubation, as assessed by a 111I release microcytotoxicity assay. NKCF adsorption to target cells and its cytotoxic activity were inhibited by some phosphorylated sugars (mannose-6PO4 and glucose-6PO4), but not by fructose-6PO4 or nonphosphorylated sugars (mannose, glucose, galactose). These results suggest a role of sugar-6PO4 at the level of interaction of NKCF with NK target cells. This was further supported by the finding that inhibition of target cell glycosylation by tunicamycin also inhibited absorption of NKCF to the target cells and direct killing by NKCF. Therefore, it appears that NKCF is a large granular lymphocyte produced factor which produces lysis as a result of the interaction with glycosylated structures on target cell membranes. Purification studies were performed to begin biochemical characterization of human NKCF. The results indicated that NKCF has an apparent molecular weight between 20,000 and 40,000 dalton. Such approaches with radiolabeled NKCF should be useful for the further study of the biochemical characteristics of human NKCF and of its mechanism of action. The ability to elicit NKCF under serum-free conditions should facilitate its testing, purification, and biochemical characterization. PMID- 4033672 TI - Effects of diethylstilboestrol-dipropionate on SCEs, micronuclei, cytotoxicity, aneuploidy and cell proliferation in maternal and foetal mouse cells treated in vivo. AB - The effect of diethylstilboestrol-dipropionate on the frequency of SCEs and micronuclei, cytotoxicity, aneuploidy and cell proliferation rates of foetal liver and maternal bone marrow cells following exposure of pregnant mice was measured. An increase in the number of aneuploid and polyploid cells was observed in both tissues. There was no effect on micronuclei frequency, SCE frequency, or cell proliferation rate. PMID- 4033673 TI - 3-Aminobenzamide sensitizes cultured Chinese hamster cells with bromodeoxyuridine substituted DNA to genetic damage induced by long-wave UV. AB - Chinese hamster cells, containing BrdUrd-substituted DNA, were irradiated in the presence of 3-aminobenzamide with short-wave UV, long-wave UV or X-rays and analyzed for induced SCEs or chromosomal aberrations. The data presented in this paper show that when BrdUrd-substituted cells are irradiated with lw-UV in the presence of 3-aminobenzamide, genetic damage is increased. Biochemical analysis shows that the molecular weight of BrdUrd-substituted DNA is reduced by this treatment. The sensitization is due to the combined action of lw-UV, incorporated BrdUrd and 3-aminobenzamide, without any involvement of inhibition of poly(ADP ribose) synthetase. No potentiation occurs when cells are irradiated with X-rays and genetic damage is decreased when cells are irradiated with UV light of 254 nm in the presence of 3AB. This decrease coincides with a reduction in the amount of induced pyrimidine dimers, detected as T4 endonuclease-sensitive sites in DNA. PMID- 4033674 TI - Characterization of DNA repair in a mutant cell line derived from ICR 2A frog cells that is hypersensitive to non-dimer DNA damages induced by solar ultraviolet radiation. AB - The level of excision repair and the inhibition and recovery of semiconservative DNA synthesis were examined following the induction of non-dimer DNA damages by solar ultraviolet radiation in a mutant cell line, DRP 36, derived from ICR 2A frog cells that is hypersensitive to these lesions. A relatively pure population of non-dimer photoproducts was produced by exposure of cells to the Mylar filtered solar UV wavelengths produced by a fluorescent sunlamp followed by treatment with photoreactivating light (PRL) which removes most of the small yield of dimers induced by the irradiation. Using a modification of the bromodeoxyuridine (BrdUrd) photolysis assay, that enhances the sensitivity of this assay, it was found that DRP 36 cells perform a significantly lower level of excision repair following the induction of non-dimer DNA damages compared with the ICR 2A cells. In contrast, the level of excision repair of 254-nm-induced dimers was similar in the two cell lines. In addition, the induction of non-dimer damages caused a greater inhibition of DNA synthesis that persisted for a longer period of time in the mutant compared with the parental cells. Hence, these results indicate that the DRP 36 cells are deficient in the repair of at least one type of solar UV-induced non-dimer lesion. PMID- 4033675 TI - Normal human bronchial epithelial cells do not show an adaptive response after treatment with N-methyl-N'-nitro-N-nitrosoguanidine. AB - Normal human bronchial epithelial cells cultured in serum-free medium were exposed to low doses o N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) to examine whether increased cellular resistance and increased activity of the DNA-repair enzyme O6-methylguanine-DNA methyltransferase could be induced. After treatment with single doses of MNNG a dose-dependent decrease in O6-methylguanine-DNA methyltransferase activity was observed, as expected for this unique repair system. The activity recovered to the starting level in about 24 h when a dose that consumed approximately 65% of the enzyme activity (0.2 micrograms/ml) was given, but did not exceed the activity in the untreated control. Furthermore, treatment every 6 h for 4-5 days with non-toxic concentrations of MNNG (0.04-0.12 micrograms/ml) did not increase O6-methylguanine-DNA methyltransferase activity. Neither was cell survival following a range of challenge doses significantly increased. Our data suggest that human bronchial epithelial cells do not adapt to MNNG. PMID- 4033676 TI - Rapid rejoining of X-ray-induced DNA single-strand breaks in tuberous sclerosis fibroblasts. AB - The formation and rejoining rates of X-ray-induced DNA single-strand breaks (SSBs) were examined in radiosensitive and non-radiosensitive fibroblast lines from patients with tuberous sclerosis (TS), and fibroblasts from normal individuals, using the sensitive and quantitative alkaline elution method. No difference was found between these cell lines in the frequency of DNA SSBs directly produced by X-irradiation at any dose up to 750 rad. Kinetic analysis of the rate of rejoining of DNA SSBs after X-irradiation at 500 rad indicated that the rate of rejoining involved at least two components, an initial fast component and a slower component. TS fibroblast lines, either radiosensitive or nonsensitive, were proficient as to DNA SSB repair, but they showed an increased rate of rejoining in the initial fast repair process, when compared to normal fibroblast lines. Although the molecular basis for the accelerated rejoining of DNA SSBs remains unknown, it is possible that the abnormality may be related to a basic defect in TS. PMID- 4033677 TI - DNA repair in lymphocytes from patients with secondary leukemia as measured by strand rejoining and unscheduled DNA synthesis. AB - The ability to repair damage to DNA was compared in 2 groups of patients having undergone treatment for leukemia, one of which developed secondary leukemia (SL), and the other without signs of secondary malignancy (treated controls). Both were related to normal controls. DNA repair was assessed in isolated peripheral lymphocytes from the patients by measuring the rejoining of strand breaks following alkylation damage to the lymphocytes or by measuring unscheduled DNA synthesis. Day-to-day variability in the assays was considerable, but findings were that 5 out of 7 SL patients had repair deficiencies as measured by their ability to rejoin strand breaks, and 5 out of 7 had increased unscheduled DNA synthesis compared to treated and normal controls. All patients with SL and 4 out of 8 treated controls had inherent strand breaks in their DNA as compared to the normal controls when measured by alkaline elution. PMID- 4033678 TI - Formation of a new mutagenic DiMeIQx compound in a model system by heating creatinine, alanine and fructose. AB - A mixture of creatinine, D-fructose and DL-alanine was heated in diethylene glycol containing 14% water for 2 h at ca. 128 degrees C. The mutagens formed were extracted with 1-butanol, and purified by cation-exchange column chromatography, C18 reversed-phase Sep-Pak treatment and reversed-phase HPLC. According to its UV absorption, mass and 1H NMR spectra, one isolated fraction was tentatively assigned the chemical name, 3,4,8-trimethyl-3H-imidazo[4,5 f]quinoxalin-2-amine (4,8-DiMeIQx). This finding is in agreement with the suggestion that sugars, amino acids and creatinine present in meat may be the precursors of the mutagenic imidazoquinolin- and imidazoquinoxalin-2-amines (IQ compounds). PMID- 4033679 TI - Induction of superoxide dismutase, chromosomal aberrations and sister-chromatid exchanges by paraquat in Chinese hamster fibroblasts. AB - We have recently shown that Bloom syndrome fibroblasts have elevated levels of superoxide dismutase activity compared to those of normal fibroblasts. Based on this observation we decided to test whether an increased rate of superoxide radical production could be responsible for the induction of superoxide dismutase and of chromosomal aberrations and sister-chromatid exchanges characteristic of Bloom syndrome. Utilizing the superoxide-generating herbicide paraquat in Chinese hamster fibroblasts, we assayed the cells for dismutase activity, chromosomal aberrations and sister-chromatid exchanges. All 3 parameters investigated demonstrated a dose-dependent increase with paraquat and, consequently, with the superoxide produced. Since the induction of the enzyme is mediated by its substrate, the superoxide anion radical, we concluded that the increased dismutase activity (in Bloom syndrome and paraquat-treated cells) may be a secondary manifestation of an overall imbalance in oxygen metabolism and that this elevated enzymatic activity is insufficient to detoxify the high superoxide levels, which results in elevated levels of chromosomal damage. PMID- 4033680 TI - Effects of pre-treatment with sodium butyrate on the frequencies of X-ray-induced chromosomal aberrations in human peripheral blood lymphocytes. AB - The effects of sodium butyrate-mediated alterations in chromatin structure on the yields of X-ray-induced chromosomal aberrations were studied in human peripheral blood lymphocytes. Unstimulated (G0) lymphocytes were pre-treated with sodium butyrate (5 mM) for 24 h, X-irradiated and then stimulated to pass through the cell cycle. Cells in their first post-radiation metaphase were scored for chromosomal aberrations. In parallel biochemical experiments nucleoid sedimentation technique was used to examine the induction and repair of DNA strand breaks. The results show that sodium butyrate pre-treatment leads to a significant increase in the frequencies of dicentrics and rings, but not of fragments. The data from biochemical studies suggest that the numbers and rates of repair of X-ray-induced DNA-strand breaks are the same in butyrate-treated and untreated cells. We therefore suggest that the observed effect is probably a consequence of butyrate-induced conformational changes in the chromatin of G0 lymphocytes. PMID- 4033681 TI - Studies on chromosome aberrations in the eggs of mice fertilized in vitro after irradiation. II. Chromosome aberrations induced in mature oocytes and fertilized eggs at the pronuclear stage following X-irradiation. AB - Cytological analysis of the first-cleavage metaphase of eggs exposed to X-rays at the mature oocyte stage or the pronuclear stage 4 h after fertilization was performed using the in vitro fertilization technique. The frequency of chromosome aberrations in irradiated mature oocytes increased exponentially with dose, the dose-response relationship being best fitted to the linear-quadratic model. On the other hand, in eggs irradiated at the early pronuclear stage, the frequency increased linearly with dose and the dose-response relationship was best fitted to the linear model. The aberrations were mainly chromosome-type (mature oocytes: 86.0% and pronuclear stage: 88.5%) and the majority were fragments in both cases. Eggs in the early pronuclear stage were markedly more radiation-sensitive than mature oocytes. A comparison of the present results with the previous ones (Matsuda et al., 1985b) showed that the sensitivities to induction of chromosome aberrations were in the order: egg at early pronuclear stage (highest) greater than mature oocyte greater than mature sperm. PMID- 4033682 TI - Genotoxic effects and DNA photoadducts induced in Chinese hamster V79 cells by 5 methoxypsoralen and 8-methoxypsoralen. AB - The induction of lethal effects and 6-thioguanine-resistant (6-TGr) mutants were studied in Chinese hamster V79 cells after treatment with the two bifunctional furocoumarins 5- and 8-methoxypsoralens (5-MOP, 8-MOP) in the presence of 365-nm radiation (UVA). The in vivo DNA-photobinding capacity of these two compounds was measured and in parallel the cross-linking capacities of 5-MOP and 8-MOP were determined using the alkaline elution technique. The results show that 5-MOP plus UVA was about 2.5 times more effective than 8-MOP plus UVA for inhibiting cell survival and for inducing the same frequency of 6-TGr mutants (10(-4]. The total number of photoinduced lesions by 5-MOP plus UVA was about 6 times higher than that induced by 8-MOP plus UVA. However, the cross-linking capacities of 5-MOP and 8-MOP were found to be within the same range at equal doses of UVA. At equal number of DNA photoadducts produced, the lesions induced by 5-MOP appeared to be less genetically active than those induced by 8-MOP. The apparently weaker genotoxicity of 5-MOP-induced lesions is likely to be due to the induction of a lower proportion of cross-links by 5-MOP at a given number of photoadducts. PMID- 4033683 TI - Tabulation and assessment of 113 human surveillance cytogenetic studies conducted between 1965 and 1984. AB - There is an increasing tendency to monitor human exposure to genotoxic chemicals by the assessment of chromosomal aberrations or sister-chromatid exchanges (SCEs) in peripheral blood lymphocytes. In order to assess the sensitivity of these techniques, and to discern minimal criteria for their conduct, a survey of 113 human lymphocyte cytogenetic surveillance studies conducted between 1965 and 1984 has been undertaken. The present survey indicates the urgent need for standardization of study protocols. It is suggested that a common method of reporting chromosomal aberrations should be adopted, and that this should be based on the system described by Scott et al. It is also suggested that a minimum acceptable size of control and exposed populations should be agreed, and that potentially important factors such as the gender, the period and extent of exposure and individual smoking habits be defined in advance of the commission of future surveillance studies. As general awareness of the possible hazard presented by exposure of man to genotoxic chemicals increases, so appropriate preventative industrial hygiene measures will be instituted. This implies that future human cytogenetic surveillance studies may yield either weakly positive or negative data. This emphasizes the current need for agreement on appropriate study protocols. The formation of a central repository for control databases, and its subsequent updating and use by those involved in human cytogenetic surveillance studies, is recommended. Minimal experimental criteria for the design of future studies are also outlined. PMID- 4033684 TI - Natural history of endemic dermatophytoses in Bosnia and Herzegovina, Yugoslavia. PMID- 4033685 TI - [Epidemiology of trichophytosis caused by Trichophyton mentagrophytes ver. gypseum]. PMID- 4033686 TI - The effect of ketoconazole on Candida albicans infection following depression of the reticuloendothelial activity with gadolinium chloride. PMID- 4033687 TI - Trichosporon beigelii: increased occurrence in homosexual men. PMID- 4033688 TI - Transport of ethanolamine and its incorporation into the variant surface glycoprotein of bloodstream forms of Trypanosoma brucei. AB - The membrane-attached form of the variant surface glycoprotein (mf-VSG) of bloodstream forms of Trypanosoma brucei is anchored to the plasma membrane by a hydrophobic C-terminal lipo-oligosaccharide containing ethanolamine. Analysis by polyacrylamide gel electrophoresis showed that several different cloned T. brucei strains (strain EATRO 110 and variants 117 and 118 of strain 427) incorporated [3H]ethanolamine into both mf-VSG and the soluble VSG derived from it, but not into other proteins. Other trypanosomatids, e.g. Leishmania mexicana promastigotes, T. cruzi epimastigotes, and T. brucei procyclic forms, did not incorporate ethanolamine into cellular proteins. Thus, [3H]ethanolamine can be used as a specific biosynthetic label for T. brucei VSG polypeptides. The time course of incorporation of [3H]ethanolamine into VSG showed a lag period of about 15 min. Double-labelling experiments using [3H]ethanolamine and H3[32P]O4 demonstrated that ethanolamine labelled only the C-terminal moiety and was not incorporated into other portions of the VSG molecule. Cellular uptake of ethanolamine occurred via a specific carrier-mediated transport system having a Vmax of 132 pmol min-1 mg-1 protein and a Km of 3.7 microM. The properties of this transport system are consistent with the possibility that ethanolamine is derived entirely from the host. PMID- 4033689 TI - Sterols of ketoconazole-inhibited Leishmania mexicana mexicana promastigotes. AB - Leishmania mexicana mexicana promastigotes grown with cholesterol, supplied in natural products as the free sterol and as cholesteryl esters, were exposed to [2 14C]mevalonate and to the antimycotic drug ketoconazole. Growth was inhibited and cholesterol and 14 alpha-methyl sterols accumulated in free and esterified forms (cholesterol much greater than 4 alpha,14 alpha-dimethylcholesta-8,24-dien-3 beta ol much greater than 14 alpha-methylcholesta-8,24-dien-3 beta-ol congruent to 14 alpha-methylergosta-8,24(28)-dien-3 beta-ol much greater than 4 alpha,14 alpha dimethylergosta-8,24(28)-dien-3 beta-ol; identified by capillary gas chromatography/mass spectrometry, and by 1H and 13C nuclear magnetic resonance spectrometry). The 14 alpha-methyl sterols were preferentially labelled with 14C. The cholesterol was unlabelled and substituted for a substantial fraction of the major product of sterol biosynthesis, ergosta-5,7, 24(28)-trien-3 beta-ol (5 dehydroepisterol), but did not replace it and did not offer remarkable protection against either growth inhibition or alteration of sterol biosynthesis. Promastigotes grown with [6-2H]cholesterol or [4-14C]cholesterol did not contain labelled forms of Leishmania sterols, or other sterols. The chromatographic and spectrometric sterol analyses and the isotopic tracer findings suggested that ketoconazole impaired the cytochrome P-450 dependent 14 alpha-demethylation of lanosterol, that cholesterol was neither biosynthesized nor metabolized, and that the physiological functions of 5-dehydroepisterol had sterol structural requirements not entirely met by cholesterol. In all these studies, L. mexicana mexicana demonstrated a sterol biochemistry remarkably similar to that of fungi. This recommends an increase in interest in antimycotic drugs as chemotherapeutic agents for leishmanial infections. PMID- 4033690 TI - An evaluation of different methods for labelling the surface of the filarial nematode Brugia pahangi with 125iodine. AB - The specificity of a range of 125I labelling techniques (Chloramine T, Iodogen, Bolton and Hunter reagent, lactoperoxidase and iodosulfanilic acid) to the surface of the filarial nematode Brugia pahangi was evaluated by autoradiography of sections of labelled worms and of dried SDS-polyacrylamide gels following electrophoresis of homogenised worm extracts. It was concluded that Bolton and Hunter reagent was not surface specific but labelled proteins throughout the body of the worm. At the light microscope level autoradiography of worms labelled using Chloramine T, Iodogen, lactoperoxidase and iodosulfanilic acid demonstrated that the 125I labelling was restricted to the worm surface. Electrophoresis and autoradiography showed that each method produced a different pattern of labelled polypeptide. A polypeptide of molecular weight 30 kDa was labelled using each method except Bolton and Hunter reagent, and appears to be a major surface component. PMID- 4033691 TI - Phosphatidylethanolamine methylation in intestinal brush border membranes from rats resistant to Trichinella spiralis. AB - Methylation of phospholipids is proposed as a mechanism to explain changes in properties of intestinal brush border membrane that coincide with development of immunity to the intraepithelial parasite, Trichinella spiralis. Methylation was measured by the incorporation of the [3H]methyl group from S-adenosyl-L [3H]methyl methionine into phospholipids. At least two enzymatic components were detected that converted phosphatidylethanolamine to phosphatidylcholine. The first, designated methyltransferase I, catalyzed the formation of phosphatidylmonomethylethanolamine from phosphatidylethanolamine and had a low Km for S-adenosyl-L-methyl-methionine (5 microM). The second, designated methyltransferase II, which catalyzed the methylation of phosphatidylmonomethylethanolamine to phosphatidyldimethylethanolamine and phosphatidyldimethylethanolamine to phosphatidylcholine, had a high Km for S adenosyl-L-methyl methionine (167 microM). Both enzymes had two pH optima, were most active at 37 degrees C and were Mg2+ dependent. A decrease in methylation activity was present in brush border membranes from rats immunized against T. spiralis. Although the synthesis of phosphatidylcholine was not significantly altered there was a substantial decrease in the formation of phosphatidylmonomethylethanolamine and phosphatidyldimethylethanolamine as compared with nonimmunized rats. Since phospholipid composition influences membrane fluidity and cell function, it is proposed that altered methylation activity may influence the characteristics of brush border membrane in the immune host. PMID- 4033692 TI - Schistosoma mansoni: effect of maintenance in vitro on the uptake and incorporation of leucine by adult worms. AB - The rates of leucine uptake and incorporation into protein by adult male and female Schistosoma mansoni were not affected by maintenance in vitro for up to 10 days' duration, despite the decline in the protein content of male and female worms of approximately 35 and 55%, respectively, during this period. The effect of maintenance in vitro was obscured in paired female schistosomes by the apparent shielding of the female tegument within the gynaecophoral canal of the male. Incorporation rates were reduced by 50% in the presence of 2 mM cycloheximide whereas uptake rates were unaffected. Adult schistosomes are unable to maintain their in vivo protein levels purely by recourse to exogenous amino acids absorbed across the tegument in vitro, and the rates of uptake and incorporation of leucine appear to reflect the changing somatic requirements of the worms and are probably not correlated with the reproductive activity of adult worms in vitro. The possible role of alimentary rather than tegumental nutrition in egg production in vivo is discussed. PMID- 4033693 TI - Inhibition of in vivo and in vitro infectivity of Leishmania donovani by tunicamycin. AB - Leishmania donovani 2S strain promastigotes were rendered non-infectious to mice and mouse peritoneal macrophages by treatment with tunicamycin, an inhibitor of N linked protein glycosylation. Concentrations of tunicamycin (1-10 micrograms ml 1) that reduced promastigote infectivity to 2% or less of control levels had little or no measurable effect on the in vitro growth of the promastigotes. Tunicamycin has no apparent effect on the entry of promastigotes into macrophages. These results indicate that the sugar residues of glycoproteins are important to the promastigote during the early stages of macrophage infection. PMID- 4033694 TI - Lectin binding to glycoproteins in the surface membrane of Schistosoma mansoni. AB - A number of lectins were assessed for their ability to bind to glycoproteins in the surface membrane of Schistosoma mansoni. The membrane polypeptides were separated by SDS-PAGE and the glycoproteins visualised by incubating the gel with radio-iodinated lectin followed by autoradiography. Most of the individual lectins bound to a variety of glycoproteins but peanut agglutinin and Dolichos biflorus agglutinin bound preferentially to a single glycoprotein of apparent molecular weight 170 000. This glycoprotein was subsequently shown to be exposed at the surface of the parasite and localised at the tubercles. PMID- 4033695 TI - Heterozygosity for homocystinuria in premature peripheral and cerebral occlusive arterial disease. AB - Premature arteriosclerosis and thromboembolic events are well-known complications of homozygous homocystinuria due to cystathionine synthase deficiency. It is unknown whether heterozygosity for homocystinuria predisposes to premature vascular disease. We explored the frequency of excessive homocysteine accumulation after standardized methionine loading in 75 patients presenting with clinical signs of ischemic disease before the age of 50:25 with occlusive peripheral arterial disease, 25 with occlusive cerebrovascular disease, and 25 with myocardial infarction. In seven patients in each of the first two groups but in none of the patients in the third group, heterozygosity for homocystinuria was established on the basis of pathological homocysteinemia after methionine loading and cystathionine synthase deficiency in skin fibroblast cultures. Because the frequency of heterozygosity for homocystinuria in the normal population is 1 in 70 at the most, we conclude that this condition predisposes to the development of premature occlusive arterial disease, causing intermittent claudication, renovascular hypertension, and ischemic cerebrovascular disease. PMID- 4033696 TI - Impaired lung function in patients with IgA deficiency and low levels of IgG2 or IgG3. AB - We examined the relation between serum levels of IgG subclasses and lung function, as determined by spirometry, lung volumes, the single-breath nitrogen test, and static recoil pressures, in 29 patients with IgA deficiency and repeated upper or lower respiratory tract infections. Four of the patients had decreased levels of IgG2, and two had decreased levels of IgG3. Two or more lung function values were abnormal in each of these six patients and also in three others with normal levels of IgG subclasses. Low levels of IgG2 and IgG3 were significantly related to abnormal lung function (P less than 0.01). The 20 patients with normal lung function all had IgG-subclass levels above the lower range. There may be a causal relation between low levels of IgG subclasses and deterioration in lung function, suggesting that patients with combined IgA and IgG-subclass deficiencies may benefit from immunoglobulin prophylaxis. PMID- 4033698 TI - Dealing with conflicts of interest. PMID- 4033697 TI - Reappraisal of temporary levodopa withdrawal ("drug holiday") in Parkinson's disease. AB - Transient withdrawal of therapy has been advocated as a method of dealing with the complications of long-term use of levodopa in the treatment of Parkinson's disease. We retrospectively examined the effect of a 10-day period of levodopa withdrawal, or "drug holiday," in 28 patients. We then compared the subsequent clinical course of these patients over one year with that of 30 other randomly selected, similar patients with Parkinson's disease. In both groups the disease progressed; there was no difference in disease severity, capacity for daily living activities, or total amounts of dopamine agonists eventually used. For some patients, it was possible to reduce dopamine agonists used immediately after the drug holiday without causing deterioration, but a pulmonary embolus and other complications occurred. Subsequent complications related to long-term dopamine agonist therapy during the follow-up period were similar in the two groups. this investigation indicates that a drug holiday carries some risk and does not improve the efficacy of levodopa therapy or prevent the problems that occur with long-term administration. PMID- 4033700 TI - Prophylactic cesarean section at term. PMID- 4033699 TI - Vascular disease and homocysteine metabolism. PMID- 4033701 TI - Therapeutic risks associated with substitution of pharmaceutical alternatives. PMID- 4033702 TI - "Red-neck syndrome" with slow infusion of vancomycin. PMID- 4033703 TI - Placental diagnosis of the "bare lymphocyte" syndrome. PMID- 4033704 TI - Hodgkin's disease in a patient with Castleman's disease. PMID- 4033705 TI - Life extension. PMID- 4033706 TI - The effect of dietary protein on the clearance of allopurinol and oxypurinol. AB - A decrease in dietary protein is known to depress renal plasma flow and creatinine clearance. Using a randomized crossover design, we investigated the pharmacokinetics of allopurinol and its principal metabolite, oxypurinol, after oral administration of 600 mg of allopurinol in six normal subjects receiving a high-protein (268 g per day) or low-protein (19 g per day) diet. For allopurinol, the area under the curve of plasma concentration versus time increased by a factor of 1.45 (P less than 0.02), the renal clearance decreased by 28 per cent (P less than 0.02), and the ratio of the clearance of allopurinol to that of creatinine (fractional excretion) was unchanged between the low-protein and high protein diets. For oxypurinol, the area under the curve increased nearly three fold (P less than 0.02), the renal clearance decreased by 64 per cent (P less than 0.02), the fractional excretion decreased by 49 per cent (P less than 0.02), and the plasma oxypurinol half-life increased nearly threefold from 17.3 +/- 1.5 (mean +/- S.E.M.) to 49.9 +/- 2.9 hours (P less than 0.02) during the low-protein diet, as compared with the high-protein diet. We conclude that with the low protein diet, the absorption, metabolism, and excretion of allopurinol were minimally altered but the total-body clearance of oxypurinol was greatly reduced because of a large increase in the net renal tubular reabsorption of oxypurinol. PMID- 4033707 TI - Sunlight exposure as risk factor for intraocular malignant melanoma. AB - In a case-control study, we compared 444 patients with intraocular malignant melanoma with matched controls to evaluate the role of exposure to ultraviolet radiation and other risk factors in the pathogenesis of this tumor. Persons born in the southern United States had a relative risk of 2.7 (95 per cent confidence interval, 1.3 to 5.9) as compared with those born in the North. Subjects with brown eyes were protected as compared with those with blue eyes (relative risk, 0.6; 95 per cent confidence interval, 0.4 to 0.8), but complexion and hair color were not important risk factors. Patients with intraocular malignant melanoma were also more likely to have spent time outdoors in their gardens, to have sunbathed, and to have used sunlamps. Rarely wearing hats, visors, or sunglasses while in the sun was a risk factor for the disease (relative risk, 1.9; 95 per cent confidence interval, 1.6 to 2.2). These data suggest that sunlight exposure is an important risk factor for intraocular melanoma. PMID- 4033709 TI - Kidney function and drug action. PMID- 4033708 TI - Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 39-1985. A six-year-old girl with diarrhea after exposure to animals. PMID- 4033710 TI - Sunlight and skin cancer. PMID- 4033711 TI - Fish consumption and mortality from coronary heart disease. PMID- 4033712 TI - Thrombolytic therapy for acute myocardial infarction. PMID- 4033713 TI - Exercise-induced menstrual disorders. PMID- 4033714 TI - Vacuolar myelopathy in patients with the acquired immunodeficiency syndrome. PMID- 4033715 TI - Public Health Service study on Reye's syndrome and medications. Report of the pilot phase. AB - Between February and May 1984, we conducted a pilot study to examine the methods for a larger study of a previously reported relation between Reye's syndrome and medications. Thirty patients with Reye's syndrome, whose diagnosis was confirmed by an expert panel, and 145 controls were matched for age, race (black or not black), and antecedent illness (respiratory infection, chickenpox, or diarrhea) and selected from the same hospital, emergency room, or school, or identified by random digit dialing. Significantly more cases (93 per cent, 28 of 30) than members of each of the four control groups or all controls combined (46 per cent, 66 of 145) had received salicylates during matched antecedent illnesses (odds ratio of all 30 cases vs. all controls = 16.1; lower 95 per cent confidence limit = 4.6). The prevalence and mean severity score of signs, symptoms, and selected events during the antecedent illness tended to be lower among cases than controls. Thus, differences in the severity of this illness between cases and controls did not explain differences in medication exposures. This pilot study suggests an association between Reye's syndrome and the use of salicylates during an antecedent illness. PMID- 4033716 TI - The incidence of adenocarcinoma in columnar-lined (Barrett's) esophagus. AB - We evaluated the risk of adenocarcinoma developing in Barrett's esophagus (esophagus lined with columnar epithelium). Mayo Clinic records were reviewed, and all cases that met predefined histologic criteria for the diagnosis of Barrett's esophagus in 1979 or earlier were included. In 18 of 122 such cases, adenocarcinoma of the esophagus and Barrett's esophagus were diagnosed simultaneously. The status of the remaining 104 cases was determined after a mean interval of 8.5 years. During this time, adenocarcinoma of the esophagus developed in 2 patients, and 24 died from other causes. We conclude that although the incidence of esophageal adenocarcinoma is increased in patients with symptomatic Barrett's esophagus, it does not occur in the majority of such patients. PMID- 4033717 TI - Antitrust law and the physician entrepreneur. PMID- 4033718 TI - How we subsidize "offshore" medical schools. PMID- 4033719 TI - Lactic acidosis associated with the therapy of acute bronchospasm. PMID- 4033720 TI - Selective antibody deficiency and recurrent pneumococcal bacteremia in a patient with Sjogren's syndrome, hyperimmunoglobulinemia G, and deficiencies of IgG2 and IgG4. PMID- 4033721 TI - Treatment of acute mountain sickness. PMID- 4033722 TI - Increased production and consumption of cane sugar in the Third World to prevent undernutrition and famine. PMID- 4033723 TI - No smoking at Group Health Cooperative of Puget Sound. PMID- 4033724 TI - Financing graduate medical education. PMID- 4033725 TI - Bottom-line health care? PMID- 4033726 TI - Antitrust enforcement in health care. Ten years after the AMA suit. PMID- 4033728 TI - The alcohol withdrawal syndrome. PMID- 4033727 TI - Detection of measles virus RNA in lymphocytes from peripheral-blood and brain perivascular infiltrates of patients with subacute sclerosing panencephalitis. AB - To clarify the relation between lymphocytes and measles virus in subacute sclerosing panencephalitis, we used in situ hybridization and a cloned measles virus DNA probe, specific for nucleocapsid protein, to detect measles virus RNA sequences in circulating lymphocytes and brain perivascular cuffs of patients with subacute sclerosing panencephalitis. Seventy to 90 per cent of peripheral mononuclear cells from three such patients were found to contain measles virus RNA sequences. In contrast, only a few infected cells were observed in four seropositive adults (0.1 to 5 per cent) and three age-matched children (10 to 15 per cent) used as controls. In one sample of brain tissue from a patient with subacute sclerosing panencephalitis, viral RNA sequences were also detected in nerve cells and in numerous cells from the perivascular infiltrates. In contrast, no hybridization was observed in brain tissue from a patient with herpetic encephalitis and from a patient with postlymphoma encephalitis. We conclude that measles virus has a strong tropism for lymphocytes and nerve cells in subacute sclerosing panencephalitis and that lymphocytes may be involved in the pathogenesis of the disease. PMID- 4033729 TI - Subacute sclerosing panencephalitis and lymphocytes. PMID- 4033730 TI - Lead as a cause of SIDS. PMID- 4033731 TI - Trends in the incidence of myocardial infarction in a large employed population. PMID- 4033732 TI - Effect of slight plasma glucose decrease on glycosylated hemoglobin in healthy subjects during caloric restriction. PMID- 4033733 TI - Failure of prednisolone to suppress carbamazepine hypersensitivity. PMID- 4033734 TI - Treatment of type I primary hyperoxaluria. PMID- 4033735 TI - Who needs more doctors. PMID- 4033736 TI - The NIH and numbers. PMID- 4033737 TI - Health policy report. Some further notes on congressional oversight of the NIH. PMID- 4033738 TI - Caffeine degradation and increased ochratoxin A production by toxigenic strains of Aspergillus ochraceus isolated from green coffee beans. AB - The growth and ochratoxin A production of Aspergillus ochraceus strains S-235-100 and IFM 0458, which were isolated from green coffee beans and glutinous rice, respectively, were examined in yeast extract-sucrose (YES) medium containing 0.1 to 1.0% caffeine. The mycelial growth and ochratoxin A formation of strain IFM 0458 was inhibited by caffeine at concentrations over 0.1%, and ochratoxin A was not produced at caffeine levels of 0.5% and 1.0%. Contrary to this, A. ochraceus strain S-235-100 produced a larger amount of ochratoxin A in the presence of 0.5% and 1.0% caffeine when grown on YES medium, reaching a maximum after 15 to 20 days of incubation. The formation of ochratoxin A by nine additional strains of A. ochraceus, three strains of A. elegans and one strain of A. sclerotiorum isolated from green coffee beans was determined on rice and ground green coffee media. A significant degree of degradation of caffeine in the green coffee medium was demonstrated with cultures of nine A. ochraceus isolates from green coffee beans. Most of these isolates showed the potential to grow on moist green coffee beans and to produce a significant amount of ochratoxins. PMID- 4033739 TI - Prototheca associated with banana. AB - Prototheca stagnora was found to be a habitant of older harvested banana (Musa sapientum) and plantain (M. paradisiaca) stumps while P. wickerhamii colonized fresh Musa sp. stumps and flower bract water of Heliconia sp. While Prototheca sp. were known to habituate woody plants, this is the first evidence that herbaceous plants also serve as habitats. PMID- 4033740 TI - Workshop: Physiological and biochemical characteristics of animal models of nutritional dependent diseases. 30 November-2 December 1983, Bad Saarow, GDR. PMID- 4033741 TI - Selection for different growth parameters in laboratory mice and its correlated effects on body composition and organ weights. AB - Body composition and organ weights were determined in male mice sampled from 4 different lines of a selection experiment: DU-6P (selected for high protein amount), DU-6 (selected for high body weight), DU-6 + LB (selected for an index combining body weight and endurance fitness) and DU-K (unselected control line). Selection was carried out under the conditions of ad libitum feeding and standardization of litter size at birth. In all 3 selection lines a significant direct selection response was shown. While fat in lines DU-6P and DU-6 + LB remained normal, it increased after selection for body weight (DU-6) significantly. Up to generation 13 the average increase of fat was 0.32% per generation. Investigations on 28 to 80 days old mice showed, that males of this line were fatter before, at and after the age of selection (42 days). After 9 generations the body weight of selected mice was significantly increased by 23 to 29%. The absolute organ weights of hearts, livers and kidneys were also significantly higher, while the relative weights of hearts and kidneys decreased. The relative liver weights were in the selected lines higher, but only the difference DU-6 vs. DU-K was significant. PMID- 4033742 TI - Some aspects of lipid metabolism in the liver of Wistar rats with fat diet induced obesity. AB - Diet-induced obesity in rats can be produced by high-fat feeding. Comparing high fat with low-fat feeding, the present study was designed to characterize the phases of development of obesity. In the dynamic phase, male rats were investigated at the age of 9-10 weeks after feeding the diets for 4-5 weeks. In the static phase, the animals at the age of 24-26 weeks were tested after 20-22 weeks of the nutritional regime. In this phase, the effects of switching high-fat to low-fat diet for 4 weeks were also examined. Fractionating lipid extracts by thin layer chromatography the concentrations of several lipids in epididymal adipose tissue, in serum, and in liver were determined. In liver, the enhancement of cholesteryl-ester (CE) concentration after high-fat feeding besides the accumulation of triglycerides (TG) is remarkable. Cell fractionation studies of the livers by differential ultracentrifugation showed the major part of the accumulated CE in the supernatant. In vitro incorporation of (1-14C)acetate and (2-14C)mevalonate into liver slices indicated that cholesterol synthesis in the liver of the obese rats was not increased. Although the offered fat diet with 0.1% of cholesterol can not be considered as high in cholesterol, the 2.5-fold higher amount of the high-fat diet in comparison with the low-fat diet (0.04% cholesterol) could be responsible for the enlargement of CE in the liver of the fat fed rats. This possibility was proved by measurement of the cholesterol absorption and transport to the liver after oral administration of (4 14C)cholesterol. Estimation of TG secretion rates of the liver using Triton WR 1339 pointed out higher rates in the obese rats in the dynamic phase. In the static phase, the rates were not different between both feeding groups, while fat restriction in the food produced a striking increase of TG secretion. It is assumed that only in the dynamic phase metabolism is able to compensate the liver TG accumulation by an enhanced transport to the adipose tissue. In the static phase this ability is diminished but not lost. PMID- 4033743 TI - Fatty acid composition of liver and adipose tissue lipids in Wistar rats with fat diet-induced obesity. AB - The influence of dietary fat on the fatty acid composition of liver and adipose tissue lipids was investigated after 4 and 19 weeks of high-fat feeding (50% fat) in comparison to low-fat feeding (3% fat), beginning in the sixth week of age. In rats fed the low-fat diet or an usual pellet diet the fatty pattern of liver triglycerides (TG) was equal to that of adipose tissue, while there were no similarities to the diet. In total liver lipids a constant fatty acid profile was observed, independently of the duration of feeding. High fat feeding results several changes in the fatty acid pattern of liver lipids. While after 4 weeks the fatty acids of liver TG more closely resembled the dietary fatty acids than those of adipose tissue, after 19 weeks of feeding the fatty acid composition of liver TG is comparable with that of adipose tissue. Not all rats fed the high fat diet rendered obese. It could be shown that in rats with higher lipid concentrations in the liver only the fatty acid pattern of liver phospholipids has been altered, while the composition of TG, which are the lipids primarily increased, was not changed. PMID- 4033744 TI - The experimental obesity by high-fat feeding--a model for evaluation of the biological value of fats. AB - The experimental obesity by high-fat feeding of rats, introduced after weaning, was found to be a suitable model for evaluation of the biological value of nutritional fats with different fatty acid composition: butter (group B), lard (L), partially hydrogenated oil (H), lard + sunflower oil 2:1 (LS). The differences in the fatty acid composition of these regimens affect: the efficiency in creating the model of obesity; the hormonal pattern of blood plasma; some metabolic pathways in liver and adipose tissue (especially in group H); the fatty acid composition of some structural, reserve and transport lipids; some biological tests indicative of membrane's phospholipid and fatty acid composition, i.e. the rate of platelets aggregation. A special attention should be paid to the striking differences in the cellularity and morphogenesis of adipose tissue in group B (hyperplastic obesity) in comparison with all other high-fat groups (hypertrophic obesity), irrespective of the identical energy and protein content of the diets. Thus, the early administration of a diet with butterfat (50% of energy) promoted a model of hyperplastic obesity, while the isocaloric diet with lard + sunflower oil caused a hypertrophic type of obesity. The authors have proved the regenerating capacity of the periepididymal fat pad in adult rats after partial lipectomy. The relative contribution of endogenic and exogenic (nutritional) factors in this process is discussed and the modifications in the cellularity of adipose tissue on these conditions are evaluated. PMID- 4033745 TI - [Cholesterol ester-composition of the adrenal glands of rats in various fat-rich diet regimes]. AB - Cells of adrenal cortex (AC) contain in about 80-90% cholesterol esters (CE), related to total cholesterol. It is assumed, that dietary fats can influence the composition of CE and hydrolytic activity of AC, leading to disorders in steroid biosynthesis. Results are presented about fatty acid composition of CE of AC from rats, fed with a fat rich diet containing different dietary fats. 5 groups and 2 subgroups of male rats at the age of 11 months were investigated: group K- control; group Oil--sunflower oil + lard; group Sch--lard; group Bu--butter; group Hy--hydrogenated oil: Every 5 animals from groups Oil and Bu were treated with dehydroepiandrosterone. Lipids of AC were extracted and analyzed chromatographically. The content of CE and other lipid classes did not differ among experimental groups and control. Differences in fatty acid composition of AC--CE, however, reflect the composition of dietary fats. Trans-isomers were detected by Ag+-thin layer chromatography. It can be assumed, that physiological barrier against trans-isomers is low. Possibly fat rich diets inhibits utilization of linoleic acid, leading to a deficit of arachidonic acid, which influences prostaglandin synthesis and causes disorders in steroid biosynthesis. Hormone treated animals showed minor differences in fatty acid composition of CE in AC in comparison to control. The results outline, that fat-rich diets with different dietary fats influence the composition of CE in AC. PMID- 4033746 TI - [Quantitative determination of ossification of fetal rat bones with graphic analysis]. PMID- 4033747 TI - Vaccine-damage damage. PMID- 4033748 TI - Statutory compensation urged. PMID- 4033749 TI - Progress on Theileria vaccine. PMID- 4033750 TI - More help required on T and B cells. PMID- 4033751 TI - Phorbol ester and sperm activate mouse oocytes by inducing sustained oscillations in cell Ca2+. AB - The parthenogenetic activation of mouse oocytes by several agents is accompanied by a large rise in the intracellular calcium concentration ( [Ca2+]i). The tumour promoting phorbol ester 12-O-tetradecanoyl phorbol acetate (TPA) activates some cellular processes which are also activated by raised [Ca2+] (ref. 2). We therefore tested TPA on mouse oocytes and found it to be a potent parthenogenetic activating agent. Recent reports suggest that TPA mimics endogenous diacylglycerol3 and can stimulate cells by activating protein kinase C without raising [Ca2+]i (refs 4, 5). We have now measured [Ca2+]i with aequorin in mouse oocytes treated with TPA. Sustained oscillations in [Ca2+]i appeared in those oocytes which were subsequently activated. We also measured [Ca2+]i during fertilization. The response began with [Ca2+]i transients as reported previously, but the transients continued in a regular pattern for 4 h. There was no rise in [Ca2+]i of the type induced by activating agents such as ethanol. One component of the fertilization response appears to be related to the TPA-induced oscillations. PMID- 4033753 TI - NIH/FDA dispute likely to delay research. PMID- 4033752 TI - Stimulated neutrophils from patients with autosomal recessive chronic granulomatous disease fail to phosphorylate a Mr-44,000 protein. AB - Phagocytosing neutrophils, monocytes, macrophages and eosinophils produce a burst of non-mitochondrial respiration that is important for the killing and digestion of microbes. Much of the information about the oxidase system involved comes from studies on patients with chronic granulomatous disease (CGD), a syndrome in which an undue predisposition to infection results from complete absence of this burst of stimulated respiratory activity. The basis of the oxidase activity is an electron transport chain, the only established component of which is a very unusual b-type cytochrome (b-245) (ref. 2). The molecular defect in the X-linked subgroup of CGD is the absence of this cytochrome b-245, which, however, appears to be normal in those subjects with the autosomal recessive mode of inheritance. In an attempt to identify an abnormality of activation, or an absence or malfunction of a proximal component of the electron transport chain in this latter group, we examined protein phosphorylation in neutrophils after activation of the oxidase with phorbol myristate acetate. All four of the patients studied demonstrated a selective lack of the enhanced phosphorylation of a protein of relative molecular mass (Mr) 44,000 (44K) that was observed in normal subjects and in two CGD patients with an X-linked inheritance. This molecule, therefore, could be an important functional component of the oxidase. PMID- 4033754 TI - Mounting pressure for reform. PMID- 4033755 TI - Water fleas as population model. PMID- 4033756 TI - False starts in translational control of gene expression. PMID- 4033757 TI - A phage repressor-operator complex at 7 A resolution. AB - The crystal structure of a complex between the DNA-binding domain of phage 434 repressor and a synthetic 434 operator shows that the protein, very similar in conformation to gamma repressor, binds to B-form DNA with the second alpha-helix of a helix-turn-helix motif lying in the major groove. PMID- 4033758 TI - Changing the binding specificity of a repressor by redesigning an alpha-helix. AB - We replaced amino acids on the 'outside', or solvent-exposed, surface of the DNA recognition alpha-helix of 434 repressor with the corresponding amino acids from the recognition helix of P22 repressor. The binding specificity of the resulting hybrid protein, as measured in vivo and in vitro, was that of P22 repressor. PMID- 4033759 TI - Reconstitution of an active surface T3/T-cell antigen receptor by DNA transfer. AB - We have introduced a full-length complementary DNA of the T-cell antigen receptor beta-chain into a mutant human T-cell line that lacked a complete beta-chain messenger RNA, had a diminished level of alpha-chain transcript and did not express surface T3- or antigen receptor. Expression of the transfected beta-chain led to a normal level of alpha-chain transcript and a structurally and functionally active T3 T-cell antigen receptor complex on the cell surface. PMID- 4033760 TI - Haemophilia B caused by a point mutation in a donor splice junction of the human factor IX gene. AB - Haemophilia B (Christmas disease) is an inherited, recessive, sex-linked, haemorrhagic condition caused by a defect in the intrinsic clotting factor IX. This disease occurs in males at a frequency of approximately 1 in 30,000. Patients differ in the severity of their clinical symptoms, and variation in the clotting activity and in the concentration of factor IX antigen in their plasma has been demonstrated. There is probably heterogeneity in the molecular defects of the factor IX gene causing the disease. Here we study a severely affected, antigen-negative patient, and show that the only significant sequence difference from the normal factor IX gene is a point mutation changing the obligatory GT to a TT within the donor splice junction of exon f. We infer that this change is the cause of the disease in this individual. In addition, we have used oligodeoxynucleotide probes specific for this mutation to demonstrate the feasibility of carrier detection and prenatal diagnosis for relatives of the patient. PMID- 4033761 TI - Attachment of transported vesicles to microtubules in axoplasm is facilitated by AMP-PNP. AB - Axoplasm extruded from the squid giant axon has been used to analyse the molecular mechanisms of intracellular vesicle transport. Using video-enhanced light microscopy, vesicle transport can be observed directly on individual microtubules at the edge of the axoplasm. Here we report that AMP-PNP (adenyl-5' yl imidodiphosphate), a non-hydrolysable analogue of ATP, reversibly inhibited vesicle transport. Moreover, vesicles in solution attach to the microtubules and form relatively stable complexes. AMP-PNP may produce this effect by binding to an ATP-binding site on the transport machinery, thereby stabilizing the motility complex that is normally formed by a transported vesicle, an ATPase and a microtubule. The effects of AMP-PNP on the vesicle transport system indicate that the enzymatic machinery of this system differs significantly from that of the actomyosin system or the dynein-microtubule system. PMID- 4033763 TI - What hope for AIDS? PMID- 4033764 TI - British nuclear workforce assessed for risks. PMID- 4033762 TI - Ethylation interference and X-ray crystallography identify similar interactions between 434 repressor and operator. AB - In the crystal structure of a repressor-operator complex (the 434 repressor DNA binding domain and its 14-base pair (bp) operator), Anderson et al. elsewhere in this issue identify six positions of likely contact between repressor protein and phosphates of the DNA backbone. At each of these positions, electron densities of protein and DNA merge. Experiments presented here indicate that intact 434 repressor approaches these phosphates very closely when it is bound to DNA in solution. Specifically, when any one of these phosphates is ethylated, repressor cannot bind to the modified operator. We also identify another position where ethylation has a significant but less dramatic effect on repressor binding, and note that in the structure, repressor closely approaches this phosphate. Our results strongly support the idea that the interactions between protein and the DNA phosphate backbone in the crystallized complex are the same as those made by intact repressor to operator DNA in solution. In addition, our results suggest that DNA is slightly bent by repressor binding. PMID- 4033765 TI - US troops and AIDS. PMID- 4033766 TI - Birthday present for digitalis. PMID- 4033767 TI - Yeast as the universal cell. PMID- 4033768 TI - Scavenger cell receptor shared. PMID- 4033769 TI - Ultrastructural localization of choline acetyltransferase in vascular endothelial cells in rat brain. AB - Furchgott and Zawadski have shown that acetylcholine (ACh) does not act directly on the smooth muscle of blood vessel walls, but rather via receptors on the endothelial cells lining the lumen, to release an endothelium-derived relaxing factor (EDRF). As it is very unlikely that neurotransmitter released from the periarterial nerves, which are confined to the adventitial-medial border, diffuses all the way through the medial muscle coat before acting on endothelial cells to release EDRF to produce vasodilatation, this discovery has been regarded as an indication of a pathophysiological mechanism, rather than a physiological one (see refs 2, 3). ACh is rapidly degraded in the blood by acetylcholinesterase, so that ACh must be released locally to be effective on endothelial cells. Here we demonstrate the immunocytochemical localization of choline acetyltransferase in endothelial cells of small brain vessels, which is consistent with the view that the ACh originates from endothelial cells that can synthesize and store it. We suggest that release of ACh following damage to endothelial cells during ischaemia contributes to a pathophysiological mechanism of vasodilation which protects that segment of vessel from further damage as well as brain cells from hypoxia. PMID- 4033770 TI - Differential inhibition of neurone-neurone, neurone-astrocyte and astrocyte astrocyte adhesion by L1, L2 and N-CAM antibodies. AB - The cell adhesion molecules L1, N-CAM and Ng-CAM have been implicated in cell cell interactions among developing neural cells. L1 and N-CAM are structurally and functionally distinct molecular entities and act synergistically in mediating Ca2+-independent adhesion between re-aggregating early postnatal cerebellar cells. N-CAM has been reported to be neurone-specific in the chicken and to mediate fasciculation of neurites and of nerve-muscle interactions. L1, which in the central nervous system has been found only on post-mitotic neurones, mediates migration of granule cell neurones in the mouse cerebellar cortex. In view of the molecules' distinct effects on cell interactions, we wondered whether different neural cell types are involved in the actions of each molecule. Here we report that L1 antigen promotes neurone-neurone adhesion. N-CAM, which is expressed on both neurones and glia, mediates neurone-neurone, neurone-astrocyte and astrocyte astrocyte adhesion. The L2 carbohydrate epitope shared between the two adhesion molecules seems to be involved in neurone-astrocyte and astrocyte-astrocyte adhesion and acts in a more than additive manner in N-CAM-mediated neurone neurone adhesion. PMID- 4033771 TI - Platelet secretory products inhibit lipoprotein metabolism in macrophages. AB - Macrophages possess a receptor that binds low-density lipoproteins (LDL) containing lysine residues modified by acetylation (Ac LDL), acetoacetylation (AcAc LDL) or malondialdehyde treatment. This receptor (referred to as the Ac LDL receptor or scavenger receptor) internalizes the bound lipoprotein. As a consequence, massive amounts of cholesteryl esters accumulate so that macrophages in culture resemble foam cells found in atherosclerotic lesions. In an effort to identify an unmodified mammalian macromolecule that binds to the Ac LDL receptor, we investigated whether platelet secretory products affect the receptor-mediated endocytosis of chemically modified lipoproteins. Platelets are a potential source of such activity because they exist in close association with foam cells in developing atherosclerotic lesions. Our study demonstrates that human blood platelets secrete a product that inhibits the binding and uptake of AcAc LDL by mouse peritoneal macrophages and the subsequent accumulation of cholesteryl esters. This is the first indication that an endogenous macromolecule interacts with Ac LDL receptor on macrophages. PMID- 4033772 TI - Cultured human endothelial cells express platelet-derived growth factor B chain: cDNA cloning and structural analysis. AB - Vascular endothelial cells have a central role in various pathophysiological responses such as acute inflammation, wound healing and atherogenesis. The anatomical position of endothelial cells between blood leukocytes and the surrounding vascular smooth muscle cells or stromal fibroblasts may intensify and focus the effects of released endothelial cell products. Endothelial cells in culture produce a platelet-derived growth factor (PDGF)-like mitogen. PDGF purified from platelets is a basic protein with an apparent relative molecular mass (Mr) of approximately 30,000 (reviewed in refs 2, 3) and is believed to comprise two polypeptide chains, PDGF-A and PDGF-B (also referred to as PDGF-1 and PDGF-2; refs 5, 6). Sequence analysis of PDGF B chain has revealed a striking homology with the predicted sequence of p28sis, the transforming protein of simian sarcoma virus. sis-Homologous transcripts have been detected by Northern blot analysis of RNA from cultured endothelial cells. However, there are no structural data available on either the protein product or the messenger RNA to establish the identity of the endothelial-derived mitogen with either chain of PDGF. Here we report the isolation and complete sequence analysis of a sis homologous complementary DNA clone from human endothelial cells, providing an opportunity to study the structure of sis as transcribed by a normal (untransformed) cell. Our results establish that normal human endothelial cells in culture express the B chain of PDGF, and that endothelial-derived PDGF B chain is synthesized as a predicted precursor polypeptide of Mr 27,281. PMID- 4033774 TI - Nuclear waste. EPA regulates at last. PMID- 4033773 TI - Light-regulated and organ-specific expression of a wheat Cab gene in transgenic tobacco. AB - Many of our most important crop plants are monocotyledons, including wheat, corn, rice and barley. No routine transformation system for monocotyledons has been reported, such as the Ti-mediated gene transfer system for dicotyledons facilitated by Agrobacterium tumefaciens. Indirect evidence suggests that Ti plasmid DNA is transferred into and expressed in A. tumefaciens-infected wound tissues of plants from Liliaceae and Amaryllidaceae, but these observations have not been extended to monocotyledons of greatest agricultural importance. Regeneration of monocotyledons is usually blocked at the callus-stage, further complicating the possibility of exploring the regulated expression of their genes, and thus preventing identification of the regulatory domains of monocotyledonous genes in a homologous nuclear background. To circumvent these difficulties, we investigated whether monocotyledonous genes can be expressed and correctly regulated in dicotyledons. We have introduced a wheat gene (whAB1.6) encoding the major chlorophyll a/b binding protein (Cab) of the light-harvesting complex into the genomes of tobacco (Nicotiana tabacum SR1) and petunia (Petunia hybrida) via a Ti-DNA-mediated gene transfer system which allows the transformed cells to regenerate into whole plants. Here we report for the first time the light-regulated and organ-specific expression of a monocotyledonous gene in transgenic dicotyledonous plants. PMID- 4033775 TI - Soviet alcoholism. Drunk driver stripped of degree. PMID- 4033776 TI - AIDS. US company rejects UK decision. PMID- 4033777 TI - Animal intelligence. PMID- 4033778 TI - Probe for muscular dystrophy. PMID- 4033779 TI - Are peptides good antigens? PMID- 4033780 TI - Susceptibility to murine lymphocytic choriomeningitis maps to class I MHC genes- a model for MHC/disease associations. AB - Susceptibility to some human diseases is linked, albeit weakly, to major transplantation antigens (HLA) encoded by the major histocompatibility gene complex (MHC). Here we have studied MHC/disease association in inbred strains of mice after intracerebral (i.c.) injection of lymphocytic choriomeningitis virus (LCMV). This route of infection leads to a lymphocytic choriomeningitis (LCM) which is not the result of direct cytopathic effects of the virus but is caused by the induced T-cell immune response: immunocompetent mice die whereas T-cell deficient mice survive. By using two plaque variants of LCMV strain UBC (refs 7,8), we found that susceptibility to LCM was dependent on the LCMV strain used ('aggressive' versus 'docile' UBC-LCMV) and on the various genes of the host mouse strains. In addition, susceptibility to LCM caused by docile UBC-LCMV was clearly linked to the murine major histocompatibility locus H-2D: in MHC congeneic C57BL/10 mice, susceptibility correlated with early onset and high activity of measurable LCMV-specific cytotoxic T cells in meninges and spleens and could be mapped to H-2D. This model shows that a severe immunopathologically mediated clinical disease in mice can be regulated directly by MHC genes of class I type and supports the notion that many MHC/disease associations directly reflect MHC-restricted and MHC-regulated T-cell reactivity. PMID- 4033781 TI - Smooth muscle alpha-action is a transformation-sensitive marker for mouse NIH 3T3 and Rat-2 cells. AB - Heteroploid mouse NIH 3T3 fibroblasts and several rat fibroblast strains (Rat-1, Rat-2 and REF-52) are cell lines of special interest in the field of carcinogenesis because of their extensive use as normal cells in transformation assays for putative cancer-causing genes. Exposure of these cells to carcinogenic chemicals or oncogenic DNA produces anchorage-independent cells with retracted cytoplasms that lack actin cables. All human fibroblast strains, normal and transformed, synthesize two electrophoretic forms of actin (beta- and gamma actin). In contrast, we discovered that early-passage mouse and rat strains synthesize abundant amounts of each of the three electrophoretic forms of actin (alpha-, beta- and gamma-actin) but mouse and rat cancer cells express only beta- and gamma-actins. We now show that in NIH 3T3 and Rat-2 fibroblasts a third actin, the smooth muscle alpha isoform, is abundantly co-expressed with beta- and gamma-actin. In every instance tested following transformation to tumorigenicity, the accumulation of alpha-actin messenger RNA and alpha-actin synthesis was greatly inhibited. Shutdown of alpha-actin expression thus appears to be a reproducible transformation-sensitive marker in rodent fibroblasts. PMID- 4033783 TI - Pain in animals. PMID- 4033782 TI - Local cytoplasmic calcium gradients in living mitotic cells. AB - Cytoplasmic free calcium has been proposed as a regulator of many microtubule mediated processes, including mitosis. It has been difficult to test this hypothesis because methods for local measurement of free Ca2+ in the living cell have not been available. We have used the fluorescent calcium indicator dye Quin 2 (methoxyquinoline-1bis(o-aminophenoxy)ethane-N,N,N',N' -tetra acetic acid), which allows such observations to be made by digital processing of fluorescent images from the light microscope. Here we report the application of this technique to the study of local Ca2+ concentrations in mitotic endosperm cells of Haemanthus sp., and show that there is transient increase in free Ca2+ at the mitotic spindle poles during anaphase. This locally high Ca2+ may provide a mechanism for the regional control of microtubules and other cytoskeletal elements during anaphase. PMID- 4033784 TI - Sahel famine. An ecological perspective. PMID- 4033785 TI - Organelle transport. A third front for cell motility. PMID- 4033786 TI - X chromosomes and dosage compensation. PMID- 4033787 TI - NSF. Change of direction afoot. PMID- 4033789 TI - FDA division to close. PMID- 4033788 TI - US textbooks. Californian setback for evolutionists. PMID- 4033790 TI - Technostress. Another Japanese discovery. PMID- 4033791 TI - Subcellular distribution of oestrogen receptors. PMID- 4033792 TI - Animals in research. US rules to be made tighter. PMID- 4033793 TI - Pain and laboratory animals. PMID- 4033794 TI - Quick-frozen crossbridges. PMID- 4033795 TI - A molecular solution to the riddle of the giant panda's phylogeny. AB - Although it is generally agreed that the giant panda (Ailuropoda melanoleuca) is a member of the order Carnivora, there has long been disagreement over whether it should be classified with bears, raccoons or as a single member of its own family. Four independent molecular and genetic measures lead to a consensus phylogeny for the giant and lesser pandas. The lesser panda diverged from New World procyonids at approximately the same time as their departure from ursids, while ancestors of the giant panda split from the ursid lineage much later, just before the radiation which led to modern bears. The giant panda's divergence was accompanied by a chromosomal reorganization which can be partially reconstructed from the ursid karyotype, but not from that of procyonids or the lesser panda. The apparently dramatic, but actually limited, distinctions between the giant panda and the bears in chromosomal and anatomical morphology provide a graphic mammalian example of the discordance of molecular and morphological (and chromosomal) evolutionary change. PMID- 4033796 TI - Induction of functional retinal projections to the somatosensory system. AB - Optic axons can be induced to form permanent, retinotopic connections in the auditory (medial geniculate, MG) and somatosensory (ventrobasal, VB) nuclei of the Syrian hamster thalamus; this occurs when the principal targets of retinofugal axons are ablated in newborn hamsters and alternative terminal space is created by partial deafferentation of MG or VB. The experimentally induced retinal projection to the somatosensory nucleus occurs by the stabilization of an early, normally transient projection. The present study was undertaken to determine whether the anomalous, stabilized retino-VB projection is functional. Newborn hamsters were operated on to produce permanent retino-VB projections and when the animals were mature, neurophysiological recordings were made in the cortical targets of VB, the first and second somatosensory cortices (SI and SII, respectively). Visual stimulation within well-defined receptive fields reliably evoked multi-unit responses in SI and SII of operated, but not normal hamsters. The representations of the visual field in SI and SII showed a partially retinotopic organization. These results demonstrate that optic tract axons can form functional synapses in the thalamic somatosensory nucleus, and suggest that neural structures which normally process information specific to one sensory modality have the potential to mediate function for other modalities. PMID- 4033797 TI - Monoclonal antibodies demonstrate protection of polymorphonuclear leukocytes against complement attack. AB - Studies on erythrocytes have shown that the formation of the membrane attack complex on a cell surface inevitably results in lysis. However, it is known that nucleated cells are much more difficult to kill with complement, although the molecular basis of this resistance has never been established. We have shown that a very early intracellular event, occurring within seconds of formation of the attack complex in the membrane, is a rise in cytoplasmic Ca2+, which can activate cell responses without cell death 5,6. Here we report the use of a monoclonal antibody to the terminal complement component C9, quantified by 125I and visualized by fluorescein, to demonstrate a protection mechanism in polymorphonuclear leukocytes (PMNs) attacked by complement, involving removal of the attack complex by vesiculation. Concomitantly, there is a Ca2+-dependent activation of reactive oxygen metabolite production without cell lysis. These findings have important implications in the evolutionary and pathological significance of the terminal components of the complement pathway. PMID- 4033798 TI - Actomyosin structure in contracting muscle detected by rapid freezing. AB - It is now widely accepted that the ATP-induced active sliding of adjacent thin and thick filaments mediated by myosin heads (cross-bridges) is responsible for muscle contraction. Despite intensive studies, the behaviour of the myosin heads during muscle contraction is still unclear. Recent progress in the rapid freezing electron microscope technique has greatly improved the temporal resolution of the images that can be obtained. Here, we report a new type of actomyosin structure captured by rapid freezing. We have analysed images from thin sections of freeze substituted rabbit skeletal muscle rapidly frozen during isometric contraction. For comparison, we also studied relaxed and rigor muscles. Our results show that, during isometric contraction, most myosin heads are regularly arrayed along the helix of the actin filaments and that this actomyosin structure appears to be distinct from that observed in rigor muscle. PMID- 4033799 TI - [Pattern and process: complementarity in biological thinking]. AB - Evolutionary theory is said to explain order in nature by a historical process. An analysis of the writings of E. Geoffroy-Saint-Hilaire shows, however, that pattern and process in nature are not based on simple, i.e. unreflected observation, but rather constitute alternative and incompatible ways of interpretation of observations according to certain methodological rules. It is concluded that pattern and process are complementary views of nature, pattern providing process with a direction, process giving an explanation for pattern. PMID- 4033800 TI - [The university between general education and professional training]. AB - The harmony of research, general education and professional training, which was an essential element of the classical German university, has been deeply disturbed by the enormous increase of student numbers. We discuss, whether the demands for a transfer of technology and for a training of an elite of specialists can be combined with the task of a helpful education for the majority of our students. As an example for a flexible solution we present the program of summer-schools ("Ferienakademieprogramm") of the Technical University of Munich. PMID- 4033801 TI - 1-Monolinolenoylglycerol specifically potentiates antitumour activity of daphnane orthoesters. PMID- 4033802 TI - Importance of contaminated food for the uptake of heavy metals in the rainbow trout, Salmo gairdneri. PMID- 4033803 TI - Mate competition between female rhesus monkeys. PMID- 4033804 TI - An electrophysiological analysis of the actions of the 3-PPP enantiomers on the nigrostriatal dopamine system. AB - Extracellular single unit recording and microiontophoretic studies were carried out in chloral hydrate-anesthetized gallamine-paralyzed rats to investigate the actions of the enantiomers of the dopamine (DA) analogue 3-(3-hydroxyphenyl)-N-n propylpiperidine, 3-PPP, on the nigrostriatal DA system. Intravenously administered (+)- or (-)-3-PPP consistently inhibited nigral DA neuronal activity; these actions were readily antagonized by haloperidol but were not affected by a pretreatment of reserpine plus alpha-methyltyrosine. In contrast to (+)-3-PPP, the (-)-enantiomer produced only partial inhibition of the majority of cells studied and was also capable of partially reversing the inhibitory action of apomorphine. A prior hemitransection of the brain did not alter the inhibitory action of either enantiomer. Whereas iontophoretically ejected (+)-3-PPP consistently reduced DA cell firing rate, similarly applied (-)-3-PPP reduced the activity of only some DA cells, while the majority were not influenced. In addition, iontophoresis of (-)-3-PPP could reduce the inhibitory effect of similarly applied DA or (+)-3-PPP. The (+)-enantiomer reduced caudate neuronal activity both after intravenous administration and iontophoresis. Intravenously administered (-)-3-PPP failed to influence or increased the activity of these neurons and reversed the inhibitory action of apomorphine. However, iontophoretically ejected drug reduced caudate cell activity and did not influence the inhibitory action of DA. The activity of non-DA zona reticulata neurons was inconsistently influenced by the 3-PPP enantiomers. It is concluded that (+)-3-PPP is a directly acting DA agonist, stimulating both DA autoreceptors and postsynaptic DA receptors. In contrast, (-)-3-PPP appears to be a partial agonist at nigral DA autoreceptors, whereas the action of the drug at putative postsynaptic DA receptors in the caudate remains to clarified. PMID- 4033805 TI - Efflux of 3H-5-hydroxytryptamine from rat hypothalamic slices by continuous electrical stimulation: frequency-dependent responses to serotonergic antagonists and 5-hydroxytryptamine. AB - Rat hypothalamic slices were incubated with 3H-5-hydroxytryptamine and superfused in the presence of paroxetine to inhibit 5-hydroxytryptamine (5-HT) reuptake. The slices were continuously stimulated electrically with rectangular pulses at varying frequencies. Continuous stimulation for up to 42 min at 1 Hz or at 3 Hz evoked a steady efflux of tritium that slowly decayed with time. The efflux produced by continuous stimulation at 5 Hz declined more rapidly with time. Continuous stimulation at 1 Hz in the presence of increasing concentrations of unlabelled 5-HT produced a concentration-dependent decrease in tritium efflux. The presence of methiothepin (0.5 mumol/l), quipazine (10 mumol/l) and (-)- but not (+)-propranolol (1 mumol/l) attenuated this response to 5-HT. From these data, the apparent pA2 values were calculated and found to be in agreement with published values. Frequency-dependent responses were determined using a "cumulative stimulation" protocol whereby the slices were subjected to three consecutive 14 min periods of stimulation at increasing frequencies (1, 3 and then 5 Hz). Unlabelled 5-HT (1 mumol/l) inhibited electrically-evoked tritium efflux more at 1 than at 5 Hz. Methiothepin (0.5 mumol/l) and quipazine (10 mumol/l) enhanced the stimulated efflux in a manner inversely related to the frequency of stimulation. Neither (+)- nor (-)-propranolol enhanced stimulated tritium efflux at any of the three frequencies tested. It is concluded that continuous electrical stimulation of rat hypothalamic slices at a low frequency provides a rapid means of obtaining apparent affinities and intrinsic activities of drugs that modify the serotonergic autoreceptor.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4033806 TI - Comparison of the anticonvulsant effects of two novel GABA uptake inhibitors and diazepam in amygdaloid kindled rats. AB - Two novel, specific inhibitors of GABA uptake, namely SKF 89976-A (N-[4,4 diphenyl-3-butenyl]-nipecotic acid) and SKF 100330-A (N-[4,4-diphenyl-3-butenyl] guvacine) were tested for anticonvulsant effects in amygdaloid kindled female rats. The anticonvulsant effectiveness of the compounds was compared with that of diazepam. SKF 89976-A and SKF 100330-A produced dose-dependent anticonvulsant effects on all seizure parameters measured in fully kindled rats, i.e. they inhibited seizure severity, increased seizure latency, and decreased the duration of motor seizures and EEG after discharges. ED 50s for inhibition of seizure severity were 4.6 and 15.1 mg/kg (0.014 and 0.045 mmol/kg) i.p. for SKF 100330-A and SKF 89976-A, respectively. For comparison, the ED 50 of diazepam was 1.9 mg/kg (0.0067 mmol/kg) i.p. Observation of behaviour indicated that the novel GABA uptake blockers exerted no side-effects in anticonvulsant doses, whereas diazepam produced sedative effects at all active dosage levels. The data demonstrate that SKF 100330-A and SKF 89976-A are potent, non-sedative anticonvulsant drugs in the kindling model of epilepsy, and these compounds thus may deserve interest as potential antiepileptic drugs with a very selective mechanism of action. PMID- 4033807 TI - The lead structure in cardiac glycosides is 5 beta, 14 beta-androstane-3 beta 14 diol. AB - The purpose of the present study was to determine the lead structure in cardiac glycosides at the receptor level, i.e. the minimal structural requirement for specific and powerful receptor recognition. Accordingly 73 digitalis-like acting steroids were characterized as to the concentration effecting half-maximum inhibition of Na,K-ATPase from human cardiac muscle under standardized turnover conditions. Since the Ki value equaled the apparent KD value, K'D was expressed in terms of the apparent standard Gibbs energy change delta G degrees' of steroid interaction with Na,K-ATPase. This allowed the use of the extrathermodynamic approach as a rational way of correlating in a quantitative manner, the potency and structure of the various steroidal compounds. The results of the present analysis taken in conjunction with relevant findings reported in the literature, favour the following conclusions. Cassaine, canrenone, prednisolone- and progesterone-3,20-bisguanylhydrazone, and chlormadinol acetate are compounds that are not congeneric with digitalis. The butenolide ring of cardenolides or the analogous side-chains at C17 beta of 5 beta, 14 beta-androstane-3 beta, 14-diol are not pharmacophoric substructures, but merely amplifiers of the interaction energy of the steroid lead. All modifications of the structure, geometry and spatial relationship between the steroid nucleus and butenolide side chain of digitoxigenin all at once weaken the close fit interaction with the steroid and butenolide binding subsites of the enzyme in such way that the cardenolide derivatives interact with the receptor binding site area in whatever orientation that will minimize the Gibbs energy of the steroid-receptor-solvent system. The "butenolide carbonyl oxygen distance model" (Ahmed et al. 1983) for the interpretation of the differences in potency of the cardenolide derivatives describes the change in interaction energy through structural modification as a function of the entire molecule. 5 beta, 14 beta-androstane-3 beta, 14-diol, the steroid nucleus of cardiac glycosides of the digitalis type, is the minimum structure for specific receptor recognition and the key structure for inducing protein conformational change and thus Na,K-ATPase inhibition. It is also the structural requirement for maximum contributions of the butenolide substituent at C17 beta and the sugar substituent at C3 beta-OH to the overall interaction energy, i.e. this steroid nucleus is the lead structure.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 4033809 TI - Effect of gallopamil on energy metabolism of the isolated perfused rat brain in the postischemic period. AB - The isolated perfused rat brain was used to demonstrate an effect of gallopamil on energy metabolism affected by ischemia. After a perfusion period of 30 min and 10 min of ischemia the isolated brain preparation was reperfused. From the onset of perfusion onwards, gallopamil (1 or 10 mumol/l) was present in the medium. The higher concentration of gallopamil accelerated significantly the restoration of the high-energy phosphates in the recovery stage: after 2 min of recirculation the ATP and the creatine-P levels were higher and the AMP level was lower in cortical tissue of drug-treated brains than in untreated controls. These results suggest that gallopamil protected brain energy metabolism against ischemic damage. PMID- 4033810 TI - [Proctectomy with preservation of continence]. PMID- 4033811 TI - [Partial softening of drinking water]. PMID- 4033808 TI - Thyroid-dependent alterations of myocardial adrenoceptors and adrenoceptor mediated responses in the rat. AB - Cardiovascular alterations in hypo- and hyperthyroidism have been ascribed to changes of noradrenergic neurotransmission. In the present study the influence of thyroid hormones on adrenoceptors in the rat heart was further characterized. The effect of artificial hypothyroidism (induced by feeding 6-propyl-2-thiouracil, PTU) and hyperthyroidism (induced by daily injections of triiodothyronine, T3) on myocardial adrenoceptor binding, catecholamines, some physiological responses, and their interdependence was examined. The density of myocardial beta-adrenergic binding sites (3H-dihydroalprenolol, 3H-DHA) was reduced after PTU (by 38%) and enhanced after T3 treatment (by up to 82%). The increase was dose- and time dependent and reversible within 4 days. No changes of the affinity of 3H-DHA to its binding sites were observed. Only L-T3 and L-T4 proved to be active, D-T3 and reverse T3 had no effect. The rise in beta-adrenoceptor density caused by T3 was prevented by concomitant administration of cycloheximide, indicating its dependence on protein synthesis. The density of myocardial alpha 1-adrenergic binding sites (3H-prazosin) was significantly reduced in the PTU group (by up to 28%) and even more distinctly by T3 treatment (by up to 50%). KD values remained unaltered. The noradrenaline content and turnover of rat hearts was significantly reduced by T3-induced hyperthyroidism. PTU treatment had no influence on content and turnover of noradrenaline. Plasma noradrenaline as well as adrenaline levels in freely moving rats were increased by PTU treatment 9- and 5-fold, respectively. In T3-injected animals no significant changes were measured. The density of adrenoceptors is known to be inversely correlated with catecholamine levels in several organs. Neither alpha- nor beta-adrenoceptor changes in the myocardium of dysthyroid rats could be attributed to such a homologous regulation, since they still occurred after chemical sympathectomy with 6 hydroxydopamine and adrenalectomy.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 4033812 TI - [Polymyalgia rheumatica: definition of a disease picture]. PMID- 4033813 TI - [Consensus conference prevention of decubitus]. PMID- 4033814 TI - [Microscopic hematuria following blunt abdominal injury]. PMID- 4033815 TI - [Traumatic diaphragmatic rupture]. PMID- 4033816 TI - [Acute suppurative thyroiditis]. PMID- 4033817 TI - [A house stands in Holland]. PMID- 4033818 TI - [Irregular erythrocyte antibodies during pregnancy]. PMID- 4033819 TI - [Pain control during childbirth, especially epidural analgesia]. PMID- 4033820 TI - [Consensus "policy regarding thrombocyte transfusions"]. PMID- 4033821 TI - [Cardiovascular risk factors in men (49 years old or younger) one year following the initial myocardial infarct]. PMID- 4033822 TI - [Restoration of facial function following intratemporal surgery]. PMID- 4033823 TI - [Poisoning caused by Datura fastuosa (ketjubung)]. PMID- 4033824 TI - [Pacemaker behavior during therapeutic irradiation]. PMID- 4033825 TI - Unusual complication of central venous catheter: a case report. PMID- 4033826 TI - The efficacy of androgen deprivation in the management of stage D-2 adenocarcinoma of the prostate. PMID- 4033827 TI - Pulmonary infarct incorrectly diagnosed as lung cancer. PMID- 4033828 TI - [Scientific evaluation of psychiatric health systems: principles and research strategies]. PMID- 4033829 TI - [Rehabilitation of psychiatrically handicapped patients in residential communities and its effect on duration of hospitalization. A controlled retrospective study]. PMID- 4033830 TI - [Perverse symptom formation as clues in the diagnostic process]. PMID- 4033831 TI - Clinical features of sporadic Legionella pneumophila pneumonia. PMID- 4033832 TI - Non-secreting extramedullary plasmacytoma with late involvement of the pancreas causing obstructive jaundice. PMID- 4033833 TI - Medical therapy of acromegaly. PMID- 4033834 TI - The use of formaldehyde as a preservative in the microscopic examination of urine sediment. PMID- 4033835 TI - Haemolysis, acute renal failure and haemolytic-uraemic syndrome. PMID- 4033837 TI - Continuous arteriovenous hemofiltration with low-molecular-weight heparin. PMID- 4033836 TI - Effects of furosemide administration on ionized calcium in normal subjects. PMID- 4033838 TI - Red cell volume and plasma sodium. PMID- 4033839 TI - Appearance of systemic amyloidosis in a chronic hemodialysis patient. PMID- 4033840 TI - Impaired intestinal absorption of riboflavin in experimental uremia. AB - Increased plasma and red blood cell concentrations of riboflavin have been reported in uremia. The possible role of altered intestinal absorption of riboflavin in the genesis of this abnormality is not known. For this reason we examined the intestinal absorption of riboflavin in rats made uremic by subtotal nephrectomy and sham-operated (control) rats in vivo using the recycling perfusion technique and in vitro using the everted-sac technique. Paradoxically, the results showed a significant impairment of intestinal absorption of riboflavin in vivo in uremic rats compared to the control group. However, no significant difference was observed in riboflavin transport in vitro. We conclude that the intestinal absorption of riboflavin is decreased in experimental uremia and cannot account for the reported increase in its plasma and red blood cell concentrations. PMID- 4033841 TI - Effect of hyperparathyroidism on cardiac function in patients with end-stage renal disease. AB - Heart studies were carried out in 7 patients with end-stage renal disease (ESRD) who underwent parathyroidectomy for secondary hyperparathyroidism. The studies, which included echocardiography and equilibrium radionuclide angiography (ERNA), were performed prior to parathyroidectomy and 2 weeks, 3 months, and 6 months following it, on a nondialytic day. Heart rate decreased from 89.3 +/- 1.3 to 81.4 +/- 1.5 min-1 (p less than 0.001) following parathyroidectomy and returned to the initial level at 3- and 6-month examination. Cardiac output decreased from 3170 +/- 68 to 2943 +/- 57 ml/min (p less than 0.01) following parathyroidectomy and returned to basal level on 3 and 6-month determinations. End-diastolic dimension (EDD), end-systolic dimension (ESD), septal and posterior wall thickness and shortening fraction (SF) as measured by echocardiography were normal prior to parathyroidectomy and remained unchanged following it. Left ventricular ejection fraction (LVEF), end-diastolic and end-systolic volumes measured by ERNA did not change following parathyroidectomy. This study suggests that hyperparathyroidism has little effect on cardiac performance and, except for a short-lived decrease in heart rate and cardiac output, parathyroidectomy does not affect cardiac performance when performed in patients with preoperatively normal cardiac output. PMID- 4033842 TI - Autonomic neuropathy in chronic renal insufficiency. Comparative analysis of diabetic and nondiabetic patients. AB - Disturbances of peripheral and autonomic nervous system function were evaluated in 37 normal subjects, in 52 patients with non diabetic chronic renal insufficiency (25 predialysis patients, 27 dialysis patients), and in 21 patients with diabetic chronic renal failure (10 predialysis patients, 11 dialysis patients). In nondiabetic patients, the predialysis group showed abnormal test results indicating parasympathetic lesions, in dialysis patients these derangements were nearly normalized. In predialysis diabetic patients, the autonomic alterations were much more extensive, corresponding to alterations of electroneurographical findings; in addition to parasympathetic lesions, sympathetic disturbances were seen. In contrast to the nondiabetic groups, in dialysis patients a deterioration of autonomic lesions was observed. In conclusion, these data indicate that deranged autonomic functions are common in uremia; they improve in dialysis patients with nondiabetic renal failure in contrast to diabetic patients; in this group the autonomic functions worsen in dialysis patients as a function of duration of diabetes and hemodialysis. PMID- 4033843 TI - Effects of high sodium dialysate during maintenance hemodialysis. AB - The effects of high sodium 144 mmol/l (mEq/l) dialysate were studied in normotensive, hypertensive and anephric chronic hemodialysis patients. Comparisons of blood pressures, weights and side effects associated with the hemodialysis procedure were made between two 6-month periods using dialysate sodium concentration of 133 mmol/l (mEq/l), followed by a high dialysate sodium of 144 mmol/l (mEq/l), each patient acting as his own control. No difference was found in the frequency of cramps or 'disequilibrium' side effects (nausea, vomiting, headache, restlessness). High sodium dialysate is beneficial for normotensive and anephric patients in reducing dialysis-induced hypotension and was not associated with any deleterious effects on long-term blood pressure control. In hypertensive patients, the benefit is less clear, and hypertension may increase. PMID- 4033844 TI - Hemodialysis-associated carpal tunnel syndrome. A clinical review. AB - The clinical features of 88 patients who developed carpal tunnel syndrome (CTS) in association with end stage renal failure and chronic hemodialysis were studied (11 original cases and 77 collected from the literature). Hemodialysis-associated CTS was found to have a 2 to 1 male predominance, to occur more often in angioaccess-bearing (86%) than in unoperated arms (48%) (p = 0.005), and to require surgical release of the median nerve in most of the cases (86%). The analysis of 48 of these patients revealed two patterns of presentation. Patients with the 'early pattern' (41.6%) developed CTS within 1 year of commencing hemodialysis; diabetes mellitus and/or severe polyneuropathy were present in at least 40%. In contrast, patients with the 'late pattern' (58.4%) developed symptoms after at least 1 year on hemodialysis; diabetes mellitus and/or polyneuropathy were present in less than 10%. CTS should be considered in any hemodialysis patient with upper extremity neurological symptoms; early diagnosis and treatment will prevent loss of hand function. PMID- 4033845 TI - Fractional oxalate clearance in subjects with normal and impaired renal function. AB - The 14C-oxalate clearance was determined in 13 healthy subjects and 22 patients with various diseases and varying degrees of renal function impairment, including 5 patients with primary hyperoxaluria (PH). The clearances of oxalate (Cox) and creatinine (Ccr) were correlated (r = 0.95). The regression line intersects the ordinate at the origin, while the regression coefficient is 2.0. This implies that the fractional Cox is constant, irrespective of the underlying disease and the degree of renal failure. Plasma oxalate (Pox), as calculated from the urinary oxalate excretion (Uox) and Cox, was elevated in patients with severely impaired kidney function and those with PH. Plasma creatinine (Pcr) and Pox were correlated as well (r = 0.83). Pox values of patients with PH were above the 95% confidence limits of the regression line. It is of practical importance that Pox can be estimated from Uox and Ccr when a 14C-oxalate clearance test cannot be performed. The reasons for the constancy of the Cox/Ccr ratio are discussed, and it is suggested that the effective renal plasma flow (ERPF) is the regulating factor for the tubular secretion of oxalate. PMID- 4033846 TI - Renal mercury content in HgCl2-induced acute renal failure in furosemide/saline protected and nonprotected rats. AB - Renal mercury content, urinary mercury excretion and renal function were studied in rats with acute renal failure (ARF) induced by subcutaneous injection of 2, 3, 6, or 10 mg/kg HgCl2. Similarly poisoned rats were protected against ARF by continuous intravenous infusion of furosemide and saline. Excellent protection was obtained in rats receiving 2,3, and 6 mg/kg HgCl2, whilst some animals developed moderate azotemia after 10 mg/kg HgCl2. Renal mercury content 48 h after HgCl2 injection did not differ appreciably between protected and nonprotected groups of rats and showed no relation to the dose of HgCl2 injected or to the degree of renal failure. Urinary Hg excretion was variable during the first 24 h after HgCl2 injection and tended to be higher with higher dosage unless the animals became anuric early on. Hg excretion during the second 24 h was independent of dosage, but was comparatively high in functionally well protected rats and low in oliguric animals with severe renal failure. Attempts at detoxication with the potent chelating agent complexon I after 6 mg/kg HgCl2 failed completely: Renal mercury content was similar to that in the other groups of rats and every single rat so treated developed severe anuric renal failure. Although dose-dependent functional injury after HgCl2 may be related to the amount of Hg reaching the kidney during the initial phase, we have to conclude that HgCl2 toxicity is unrelated to the amount of Hg found in renal tissue at 48 h. Furthermore, furosemide/saline protection does not act through increasing urinary Hg excretion or decreasing the amount of toxin accumulating in renal tissue. PMID- 4033847 TI - [Intracisternal length of cranial nerves 7-12]. AB - The course of the seventh to twelfth cranial nerves in the posterior fossa is described. The relation between the nerves and the cranial vessels, as well as their importance in practical medicine are discussed. PMID- 4033848 TI - [Experimental-morphologic study of depressed fracture of the skull. Experimental model]. AB - Experimental skull bone models were made and depressed fractures were created. The morphological reactions of the skull bone models were observed to be the same as in human skulls, that is, that the fractures of the inner side were always larger than those of the outer side as a result of the direction of the impacting forces (a so-called classical type of reversed "V" form). The reason for the reversed "V" form of the depressed human skull fractures was discovered by means of these model studies. The reversed "V" form is due to the "HSH" morphological structure. It will be now be necessary to correct the error in textbooks regarding the depressed fractures, especially morphological illustrations. PMID- 4033849 TI - [Are there sport-specific craniocerebral traumas?]. AB - The incidence of sports accidents is on the increase. The authors examined the question whether this is also true of craniocerebral injuries during sports activities. For this purpose they studied and assessed all grade I and II craniocerebral injuries treated during 1982 at the departments of Surgery and Neurosurgery at the University of Gottingen. The craniocerebral injuries had a share of 13.5% in the total incidence of Sports accidents. This figure is markedly above the comparative figures quoted so far. The incidence of craniocerebral trauma varies from one sports discipline to another, depending on the popularity of the particular sport. However, a comparison with data published in the literature shows that craniocerebral trauma is the most frequent sports injury in all disciplines in which the head is particularly exposed. PMID- 4033850 TI - [Intracranial pressure measurement in large skull defects]. AB - We measured the intracranial pressure continuously for a period of four days before and after cranioplasty in 12 patients with skull defects larger than 100 cm2. The results were obtained by epidural monitoring. The device used was the "Hellige" pressure measuring device (modified according to Gobiet). We found an increased cranial pressure in more than half of the patients (7). In addition the same patients showed the most marked neurologic and psychic changes. A significant return to normal of the intracranial pressure was noticed in all these patients after the closure of the skull defect. Progressive improvement in the clinical symptoms was also seen. The pathogenesis of this phenomenon has not been completely explained. Several authors consider that an important factor is the difference between the intracranial and the atmospheric pressure, However, we suggest that another important factor is the cicatricial changes ("scar plate") occurring between the cortex, dura and the skin, which exerts pressure on the skull contents. Previously, the neurological symptoms which appeared after a period of time in patients with large skull defects were attributed to other causes. It is only during the past decades--thanks to progress in neuroradiologic diagnostics--that a pathoanatomical correlate been found for these changes. PMID- 4033851 TI - An improved method for stainless steel wire mesh cranioplasty. AB - A method for stainless steel wire mesh cranioplasty is described. The method has proved simple and quick. Cosmetic results have been very good and no complications have been observed so far. This method seems particularly suitable in very large skull defects. It seems to reduce the incidence of the major complications of the wire mesh cranioplasties, viz. lifting of the margins, depression of the prosthetic vault and electrolytic interference with the circulating fluids. PMID- 4033852 TI - Acute bilateral extradural haematomas in an adult. AB - A case of acute bilateral extradural haematomas in an adult head-injured patient is presented. The literature concerning such an extremely rare condition is reviewed. PMID- 4033853 TI - Acute extradural haematoma following trivial trauma in a case of osteogenesis imperfecta. AB - A case of an extensive extradural haematoma as a complication in a patient with osteogenesis imperfecta is reported. The significance of careful appraisal and post-traumatic, neurosurgical observation of patients with osteogenesis imperfecta and a history of recent, albeit seemingly trivial, head injury is discussed. PMID- 4033854 TI - [Evaluation of 138 fractures of the cervical spine during a recent 5-year period (1979 to 1983). Therapeutic approaches]. AB - 138 cervical spine fractures are reviewed during a recent period of 5 years (1979 1983). Their frequency stay high. The serial concern 67% of men and 33% of women. We observe a peak age between 20 and 30 (23%). 65% of lesions are caused by a traffic injury, 27% by a falling down, 10% by a diving. 45% of cases interest the upper cervical spine (C1-C2) with a high proportion of odontoid process fractures (60%) and Hangman's fractures (30%); 54% of cases concern the lower cervical spine (C3-C7) with an important part of fracture-luxation (72%), specially C5-C6 (35%). Clinically, we note almost a same part of fractures without neurological disturbances (54%) and with neurological abnormalities (46%). In this situation, the sensitive and motor loss are often severe (78%). In 40%, the injuries are polytraumatism and association spine lesion, cranio-cerebral lesion is the most frequent (61%). In upper cervical spine fractures, after Crutchfield or Gardner traction, posterior fixation was performed (62%). The treatment was conservative in 30%. In lower cervical spine lesions, a secondary surgical approach by an antero-lateral way was made (53%). The treatment was initially surgical in 13% and conservative in 28%. The mortality rate of this pathology is important (22%; i.e. 30 deaths on 138 cases). PMID- 4033855 TI - [X-ray computed tomographic and angiographic aspects of venous angiomas of the brain. Apropos of 15 cases]. AB - Clinical, computed tomography and angiography investigations were conducted in 15 cases of venous angioma of brain. These rare malformations (70 cases reported) are often asymptomatic or are revealed by the onset of epileptic seizures. The scanner produced images suggestive of a vascular malformation in 80% of cases. However, the purely venous character of the angioma and its exact site require confirmation supplied by angiography only, the lesion provoking characteristic images from the latter examination. PMID- 4033856 TI - [Effects of cranioplasty on neurological function and cerebral blood flow]. AB - The authors present a review of their experience of cranioplasty in cases showing of skull defects. Forty recent case reports were retained out of a total of 125 cases and of these, 15 showed neurological deficiency prior to cranioplasty. In 7 out of these 15 cases cranioplasty appeared to have no effect, but in the 8 remaining cases, an improvement in the neurological condition was observed. In connection with these clinical observations, a recent study of a small group of patients with skull defects used the Xenon 133 inhalation method to investigate cerebral blood flow. In all cases these was a significant postoperative improvement in cerebral blood flow. The rate varying from 15 to 30% and this improvement was even observable in the case of small skull defects of the order of 10 cm2. The mechanism giving rise to such improvements is discussed; it may be related to cerebral hemodynamic normalization after skull restoration. The improvement in cerebral blood flow brought about by cranioplasty in all the cases studied suggests that this technique may be important not only for simple skull repair but also to improve neurological function. PMID- 4033857 TI - [Treatment of spastic foot by selective neurotomy of the tibial nerve. Results of a series of 31 cases]. AB - A large number of patients suffering from various neurological diseases remain disabled because of spastic disorders in their foot. These disorders--which are responsible for abnormal postures and painful disturbances for walking and standing--can be corrected by an effective procedure: the so-called Selective Neurotomy of the Tibial Nerve (T.N.), developed in its modern form by Gros in 1972. The procedure aims at sectioning the T.N. branches corresponding to the muscles, the spasticity of which is considered harmful, i.e. the soleus (and/or gastrocnemius) nerves for equinus and ankle clonus, the posterior tibialis branch for varus, and the flexor fascicles for tonic flexion of the toes. After dissection of each T.N. branches at the lower part of the popliteal region and their identification with bipolar electro-stimulation, the selected nerves are sectioned partially (about two-third of their caliber) under the operative microscope. The present series consists of 37 operations--performed 25 times unilaterally and 6 bilaterally--in 31 patients, 17 to 68 year old (39 on average). In 11 patients spasticity was from spinal cord origin and in the 20 others from vascular or traumatic cerebral damages. The spastic disorders- installed for 2 to 17 years (4 on average)--were due to one, several or all the following components: equinus, ankle clonus, varus, flexion of the toes. Surgery obtained complete suppression of the disabling spastic components, total pain relief and consequently improvement of the residual voluntary movements by achieving balance between agonist and antagonist muscles, in 33 out of the 37 cases, i.e. in 91% of the patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4033858 TI - [Spontaneous dissection of the extracranial internal carotid artery. Apropos of 3 cases. Usefulness of preventive occlusion-anastomosis]. AB - Authors point out three observations of spontaneous dissection of cervical internal carotid artery (I.C.A.) with various evolution. They emphasize on evolutivity of residual aneurysms and necessity to purpose a preventive treatment of secondary projections. PMID- 4033859 TI - [Temporary bypass in carotid surgery; peroperative study of various metabolic parameters and the EEG]. AB - Out of a whole of patients of nearly 1000 reconstructive operations of the extracranial carotid artery, which were carried out by a systematic application of the intraluminal shunt, 32 selected patients with extracranial stenosis of the internal carotid artery were examined intraoperatively as to the following parameters of the internal carotid artery and the internal jugular vein: pH, pCO2, pO2, B.E. and the lactate were determined as well. Statistic analysis shows a significant increase of the arteriovenous difference of the lactate from the first to the second and from the first to the third sample. PMID- 4033860 TI - [Use of a universal plate in osteosynthesis of the cervical spine by the anterior approach]. PMID- 4033861 TI - Effects of neonatal toluene exposure on the development of evoked and spontaneous cortical activity in the rat. AB - The effects of neonatal toluene exposure on the development of cortical evoked responses to sciatic nerve and light stimulation, as well as the spontaneous Electrocorticogram (ECoG) of frontal and occipital regions, were studied in rats at different developmental ages. The major findings following the solvent exposure were a significant prolongation in the mean peak latencies of both primary and secondary cortical evoked responses the effects being more severe in the sensorimotor area than in the visual cortical region. Additionally the experimental animals did not show significant differences in the average frequencies histograms of the ECoG in both neocortical areas when compared with control littermates. The data suggest that early toluene exposure was primarily affecting those brain structures underlying locomotor abilities than those related with the functionality of the CNS visual centers. PMID- 4033862 TI - The effects of prenatal methylazoxymethanol acetate (MAM) on holeboard exploration and shuttle avoidance performance in rats. AB - Forty pregnant rats were given an IP injection of either 0, 14, 22, or 30 mg/kg of MAM on day 15 of gestation. One animal of each sex from each litter was tested between 80 and 90 days of age in a holeboard mounted on a stabilimeter. An additional animal of each sex from each litter was tested between 110 and 120 days of age in a two-way shuttle avoidance task. In the holeboard task, prenatal treatment with MAM resulted in an increased frequency of dipping which was accompanied by an increased number of transitions between holes, rather than stereotypy. Altered patterns of exploratory behavior over the course of the test session were also evident in MAM treated offspring as compared to controls. The 22 mg/kg group tended to show less of a decrease in their activity levels over the course of the session than the other groups. In the shuttle avoidance task, prenatal treatment with MAM resulted in a facilitation of avoidance performance as compared to controls. In addition, increased activity (as measured by intertrial interval crossings) was evident in MAM treated offspring, while escape latencies were equivalent across the groups. However, the pattern of results suggest that the facilitated avoidance performance cannot be accounted for by the increased activity. These results are discussed in terms of various hypothesis which may account for the behavioral deficits shown by MAM treated offspring. PMID- 4033863 TI - Behavioral and neuropathological effects of prenatal methylmercury exposure in mice. AB - Pregnant C3H/HeN mice were orally administered a single dose of 20 mg/kg methylmercuric chloride on one of days 13 through 17 of pregnancy. They were allowed to give birth and the newborn mice were foster mothered, but the weaning rate was low. Long-term behavioral impairment was manifest in mice of every treated group. The righting movement was mildly disturbed when animals were dropped from about 40 cm high. The tail position was low during walking. Some animals showed strong flexion of the hind limbs when held by the tail. Spontaneous locomotor activity was reduced. At 10-12 weeks of age, the animals were sacrificed and the brain was histologically examined. The brain weight was reduced. The nucleus caudatus putamen was slightly reduced in size leaving the lateral ventricles dilated. Cerebellar folial patterns were slightly simplified. These neurobehavioral symptoms and pathological changes tended to be comparatively more severe in animals treated on days 13 and 14 of pregnancy than those of the other groups, but the differences were small. PMID- 4033864 TI - Effects of triethyltin and its interaction with d-amphetamine and chlorpromazine on responding under a multiple schedule of food presentation in rats. AB - Effects of triethyltin (TET) were studied in rats performing under a multiple fixed-ratio 30 fixed-interval 5-min schedule of food presentation. A dose of 1.0 mg/kg TET produced only marginal effects on responding. A dose of 3.0 mg/kg suppressed responding 3 hours after administration, but responding returned to control levels by the next day. During a period 2 to 6 weeks after the 3.0 mg/kg dose, small rate increases were observed for fixed-interval responding. The 5.6 mg/kg dose eliminated responding under both schedule components and all the animals died on the fourth day. Rats were also given d-amphetamine and chlorpromazine before and beginning six weeks after 1.0 and 3.0 mg/kg TET treatment. Both doses of TET attenuated the rate-increasing effect of d amphetamine on fixed-interval responding, but d-amphetamine dose-effect curves determined before and after TET administration differed significantly only for 3.0 mg/kg dose of TET. Chlorpromazine dose-effect curves did not differ significantly before and after TET treatment. PMID- 4033865 TI - A comparison of physostigmine and soman using taste aversion and nociception. AB - The effects of a reversible (physostigmine) and an irreversible (soman) acetylcholinesterase inhibitor were compared in terms of nociception using the rat tail flick (TF), and hot plate (HP) tests. The conditioned taste aversion (CTA) procedure was employed to evaluate the stimulus properties of these drugs. In all procedures physostigmine salicylate was administered at doses of 0.20, 0.32, 0.45, or 0.65 mg/kg, IM. Soman was administered at doses ranging from 40 to 80 microgram/kg, IM. Using either TF or HP, physostigmine and soman were evaluated at 40 min following injection. Both physostigmine and soman produced dose-related effects on each measure of nociception. The median effective dose of physostigmine was 0.27 mg/kg on TF and 0.55 mg/kg on HP. For soman, the median effective dose was 54 micrograms/kg on TF and 52 micrograms/kg on HP. In the CTA procedure, a novel, saccharin sweetened solution was paired with either physostigmine or soman. Three days later rats were offered a choice of saccharin or tap water. Both soman and physostigmine produced dose-related CTAs over the range of doses studied. Whereas the ED50 for soman was 59 micrograms/kg with significant effects at doses of 60 micrograms/kg or more, physostigmine produced effects at doses of 0.45 mg/kg or greater (ED50 = 0.05 mg/kg) with no additional changes in saccharin preference beyond 0.45 mg/kg. The data suggest that these experimental procedures, TF, HP, and conditioned taste aversion may be employed to evaluate the behavioral toxicity of physostigmine and soman. PMID- 4033866 TI - Validation of human behavioral tests using ethanol as a CNS depressant model. AB - This study evaluated the sensitivity of a battery of tests proposed for use in determining the depressant effects of chemicals on human central nervous system (CNS) function. The first step in the development of such tests was to determine if the tests could detect the effects produced by a known CNS depressant, ethanol. Five behavioral tests, digit span memory, simple reaction time, tachistoscopic perception, flicker fusion and anticipation timing (velocity estimation) were evaluated to determine their sensitivity to the effects of ethanol at blood levels between 0.05-0.06%. Thirty-one adult male volunteers received 0 and 1.4 ml 100 proof vodka/kg body weight according to a double-blind crossover design. Tests were conducted before treatment and between 30 and 70 minutes after an ethanol or control drink was ingested. Multivariate analysis of variance (MANOVA), using composite scores representing the individual tests, indicated that the battery as a whole detected statistically significant ethanol effects. Repeated measures analysis of variance (ANOVA) comparing performance after drinking ethanol to control performance on each of the individual tests indicated a significant decrement in reaction time, tachistoscopic perception and anticipation timing. PMID- 4033867 TI - Factors affecting the outcome of maternal alcohol exposure: II. Maternal age. AB - Despite relatively comparable amounts of alcohol ingestion, not all women who drink excessively give birth to children with fetal alcohol effects. The present study evaluated how maternal age affects the outcome of pregnancy in maternal rats of different ages. All dams were nulliparous and were 66, 121 or 156 days at time of treatment. Alcohol was administered at a dose of 3.5 g/kg, twice daily on gestation days 11-21. Alcohol had a greater impact on offspring born to older- and middle-age dams than to younger dams on a number of attributes including neonatal mortality and birth weight. PMID- 4033868 TI - Effects of acrylamide on multiple behavioral endpoints in the pigeon. AB - Little is known about acrylamide's effects on cognitive function in animals. Twelve pigeons were trained to stable levels of performance. We then determined the effects of subchronic exposure (p.o.) of 0, 20, and 60 mg/kg/day of acrylamide monomer on (1) duration discrimination responding; (2) fixed-interval performance; and (3) shape discrimination responding. Sixty mg/kg/day caused rapid impairment on all tests; recovery of various endpoints varied from 2 or 3 days to more than 4 weeks. Response latency recovered much more rapidly than the accuracy of duration discrimination. Measures of responding and discrimination recovered at approximately the same time for the FI and shape discrimination. FI response rate remained elevated post-acrylamide. Administration of 20 mg/kg/day for 90 days produced a consistent, but not significant, decrease in the accuracy of duration discrimination. Acrylamide affects a variety of behavioral processes involving sensory, motor and associative functions. PMID- 4033869 TI - Immunoblot identification of glial fibrillary acidic protein in rat sciatic nerve, brain, and spinal cord during development. AB - The appearance of the glial fibrillary acidic protein (GFAP) during embryonic and postnatal development of the rat brain and spinal cord and in rat sciatic nerve during postnatal development was examined by the immunoblot technique. Cytoskeletal proteins were isolated from the central and peripheral nervous system and separated by SDS slab gel electrophoresis or two-dimensional gel electrophoresis. Proteins from the acrylamide gels were transferred to nitrocellulose sheets which were treated with anti-bovine GFAP serum and GFAP was identified by the immunoblot technique. GFAP was present in the embryonic rat brain and spinal cord at 14 and 16 days of gestation respectively. The appearance of GFAP at this stage of neural development suggests that the synthesis of GFAP may be related to the proliferation of radial glial cells from which astrocytes are derived. It is also feasible that GFAP provides structural support for the radial glial cell processes analogous to its role in differentiated astrocytes. GFAP was found to be present in rat sciatic nerves at birth and at all subsequent stages of development. These results indicate that some cellular elements in the rat sciatic nerve, such as Schwann cells, are capable of synthesizing GFAP which is immunochemically indistinguishable from its counterpart in the central nervous system. Thus it appears that GFAP is present both in the central and peripheral nervous system of the rat when the glial cells synthesizing GFAP are still undergoing differentiation. PMID- 4033872 TI - Isolation and purification of myelin proteolipid protein using high speed gel filtration in sodium dodecyl sulfate. AB - Small and preparative gel filtration columns were studied for high pressure liquid chromatography of myelin proteins in sodium dodecyl sulfate. The preparative column proved useful for isolating and purifying proteolipid protein almost free (0.3-0.5%) of myelin basic protein as demonstrated by SDS-PAGE, MBP RIA, and immunoblotting. The small columns were not as useful as SDS-PAGE for analytical purposes. PMID- 4033870 TI - Properties of acetylcholinesterase and non-specific cholinesterase in rat superior cervical ganglion and plasma. AB - Amphiphile dependency, solubility in aqueous solutions, and sensitivity to proteolysis of acetylcholinesterase (AChE) and nonspecific cholinesterase (nsChE) in the rat superior cervical ganglion were studied and compared to properties of soluble plasma cholinesterases. Ganglion AChE shows strong amphiphile dependency: an amphyphilic substance must be present in the homogenizing medium in order to obtain maximal apparent enzyme activity. Apparent activity of AChE solubilized in Ringer's solution was also increased after subsequent addition of a detergent. The 4 S molecular form, predominant in this extract (corresponding to the fastest electrophoretic band), is very sensitive to papain proteolysis but can be protected by a detergent. This molecular form therefore carries an important hydrophobic domain and is probably membrane bound in situ. The 10 S form of ganglionic AChE, extracted in Ringer's solution, is probably a soluble enzyme since, like soluble plasma enzymes, it is not amphiphile dependent and is rather resistant to proteolysis. Ganglion nsChE is more water soluble, less amphiphile dependent and more protease resistant than AChE. PMID- 4033871 TI - Neurite-promoting factors from a sympathetically innervated target tissue. AB - Previous studies have demonstrated that various cell types can produce and secrete polyornithine-attachable neurite promoting factors when cultured. This study describes an endogenous source of polyornithine-attachable neurite promoting factors. The active material extracted from an avian smooth muscle, the expansor secundariorum, is able to enhance neurite outgrowth from embryonic chick sympathetic neurons when applied to a polyornithine substrate. Unlike other polyornithine attachable factors, the material is also able to support the neurons for at least 72 hr in the absence of any added survival factors. Partial purification of the active material was achieved by affinity chromatography on polyornithine-Sepharose. The findings support the proposal that neurite promoting factors may have a definite physiological role in addition to their well established in vitro activity. PMID- 4033873 TI - 2,5-Hexanedione and acrylamide produce reorganization of motoneuron perikarya. AB - During acrylamide and hexacarbon exposure few changes have been reported in motoneuron perikarya. In the present study, light microscopic examination of lumbar motoneurons from rats intoxicated with either 2,5-hexanedione (2,5-HD) or acrylamide showed relatively few nonspecific changes compared to controls. However, ultrastructural study of 2,5-HD-intoxicated perikarya revealed a range of cytological reorganization: nuclear eccentricity and capping, reduced numbers of large Nissl bodies, and mitochondrial hypertrophy and hyperplasia. In 2,5-HD intoxicated perikarya, computer-assisted stereologic analysis demonstrated a significant increase in the volume density of mitochondria. Ultrastructurally, acrylamide-intoxicated perikarya showed a marked reduction in the size of Nissl bodies. Stereologic analysis showed reductions in Nissl bodies, granular endoplasmic reticulum and Golgi complexes, and an increase in mitochondria. Taken together, these qualitative and morphometric changes, which were not obvious on light microscopic examination, imply significant reorganization of perikaryal metabolism. PMID- 4033874 TI - Irradiation and BCNU effects in the stroma in a rat transplanted glioma model: analysis of cerebral tumor bed effect. AB - F-344 rats were treated with whole-brain fractionated or unfractionated 137Cs at several time intervals up to 6 weeks before they received intracerebral grafts of an ethylnitrosourea-induced rat astrocytoma (36B-10). Rats treated with a single dose of 18 Gy at 3- and 2 week intervals prior to tumor implantation died earlier than unirradiated control tumor recipients (P less than 0.05, log rank sum test). Delivered 2 weeks prior to tumor grafting single doses of 10, 15, and 20, but not 5 Gy also reduced animal life span (P less than 0.05). Similarly, a total dose of 38 but not 28.5, 19, or 9.5 Gy, each delivered in five daily fractions 2 1/2 weeks before tumor grafting, shortened survival (P less than 0.05). Chemotherapy with 1,3-bis(2-chloroethyl)-1-nitrosourea (13.3 mg/kg) alone or in combination with a single-dose of irradiation of 18 Gy 3 weeks preceding transplantation showed no effect on animal survival. Unirradiated control tumors demonstrated sheets of densely-packed isomorphic astrocytes, perivascular brain parenchymal invasion, sparse, thin-walled vasculature, frequent mitoses, but little necrosis or hemorrhage. The tumors of rats irradiated before transplantation showed large areas of confluent necrosis associated with microvascular thrombosis, edema, and multifocal acute hemorrhages. These survival results and morphological changes indicate that the cerebral tumor bed effect involves early animal death and extensive morphological changes in the tumors; and they suggest that tumor cell death in irradiated brain tumors may, in part, result from radiation-induced vascular injury. PMID- 4033875 TI - Intracranial malignant teratoma. AB - A case of malignant teratoma arising near the third ventricle in an adult is reported. It represented a true teratoma containing elements of all three germ layers of which two, namely the mesenchymal and endodermal elements have undergone malignant change. It was characterized by rapid recurrences after two operations with death occurring shortly after the second operation. PMID- 4033876 TI - Magnetic resonance imaging in syringomyelia. AB - Myelography and myelography assisted with computed tomography have been the most commonly used radiographic methods in the study of syringomyelia. These studies have never been entirely reliable in demonstrating the syrinx cavity and its relationship to other intracranial structures. During the 1st year of operation of the magnetic resonance imaging facility, the syringomyelic cavity was demonstrated in 15 patients who all had typical clinical signs and symptoms associated with syringomyelia. Nine cases were syringomyelia with Chiari malformation. One case showed additional hydrocephalus. Four cases were idiopathic, and 1 case was remotely posttraumatic. Magnetic resonance imaging, although it is in its infancy, already promises to be the most important radiographic technique for syringomyelia because it provides an anatomically truthful visualization of the sagittal plane of the cervical cord and can demonstrate the syrinx cavity and its relationship with the cerebellar tonsils, the 4th ventricle, and other related structures. PMID- 4033877 TI - Complications of cerebral revascularization with autogenous vein grafts. AB - Autogenous veins were used for cerebral revascularization 29 times. There were 17 long grafts to the cortex and 12 shorter grafts for reconstruction of cervical vessels. Of the long cortical grafts, 5 occluded and 3 patients developed intracerebral hemorrhage. With the shorter grafts, all remained patent and there were no hemorrhagic complications. A combination of a relatively low flow rate and endothelial damage in the graft was thought to be largely responsible for early graft failure. Revascularization of an infarct and hypertension were implicated in cases with intracerebral hemorrhage. PMID- 4033878 TI - Myxomatous degeneration of the lumbar intervertebral disc. AB - Sixteen patients were operated on for lumbar pain and pain radiating into the sciatic nerve distribution. In all 16, when the anulus fibrosus was incised, soft, gray disc material extruded under pressure like toothpaste being squeezed from a tube. This syndrome of myxomatous degeneration is a distinct entity, different from classical fibrotic disc degeneration or herniated nucleus pulposus. Surgical removal associated with partial facetectomy produced excellent results. The concept of incompetence of the anulus fibrosis is discussed. PMID- 4033879 TI - Axis fractures: a comprehensive review of management and treatment in 107 cases. AB - The combination of movement, location, and anatomy of the axis predisposes it to multiple and varied fracture/dislocations distinct from other vertebrae. We examine all forms of axis fractures and address the appropriate treatment for each specific fracture type. In a retrospective review of 625 cervical spine fractures during an 8-year period, we found 107 axis fractures. There were 25 hangman's fractures (23%), 59 odontoid fractures (55%), and 23 miscellaneous fractures (22%). Each case was characterized by age, sex, the presence of associated injuries, presenting symptoms and findings, initial treatment, and results of that treatment. Excluding 6 early deaths, 90 of 101 patients were located for a median follow-up of 3.2 years. We found that 17% of cervical fractures involve the axis. Axis fractures have a high association with head and other cervical spine injuries, 40% and 18%, respectively. Few neurological deficits result from a fracture of the 2nd cervical vertebra. Hangman's fractures are effectively treated with external stabilization, preferably with a halo vest. We noted a shorter period of treatment using the halo vest as compared to the SOMI brace. Nonunion occurred in 26% of odontoid Type II fractures, but occurred in 67% of those with dens displacement of 6 mm or greater, regardless of age or direction of dislocation. We recommend early surgical therapy for this subgroup. There is no correlation between age and the rate of nonunion. In patients with odontoid Type II fractures with dens displacement of 0 to 5 mm, fusion occurs with external stabilization alone. Odontoid Type III fractures are one-half as common as Type II fractures, and all heal well with external stabilization. Twenty-two per cent of acute axis fractures are not hangman's or odontoid fractures. Miscellaneous fractures of the axis generally do well with external stabilization and immobilization. PMID- 4033880 TI - A mathematical model for the mechanics of saccular aneurysms. AB - We constructed and discussed a mathematical model of intracranial saccular aneurysms based on the static mechanics of hollow vessels and were able to focus on three variables that are fundamental to the process of enlargement and rupture of these lesions. They are blood pressure (P), wall strength (sigma), and total wall substance (VT), which, if assigned values of 150 mm Hg, 10 MPa, and 1.0 mm3, lead to model-predicted values of 8 mm for the diameter and 40 micron for the wall thickness for the critical geometry of aneurysmal rupture. These are quantitatively similar to published measurements. The model is based on the assumption of a uniform thin spherical shell for the saccular aneurysm. The interrelationship of the variables, expressed in the equation for critical size at rupture (dc) (i.e., dc = [4 sigma VT/(pi P)]1/3), draws attention to the need for quantitative studies on aneurysmal geometry and on the stereology of the structural fraction of the aneurysmal wall. We concluded that tissue recruitment from around the initial site or hypertrophy of the wall tissue is commonly involved in the aneurysmal process. We identify the paradox of elastic stiffness and stability, which are characteristic of autopsy specimens in the laboratory, in contrast to plastic behavior and irreversible strain, which are essential to the natural process of enlargement of saccular aneurysms. PMID- 4033881 TI - Paranasal sinusitis: a common complication of nasotracheal intubation in neurosurgical patients. AB - Sinusitis secondary to nasotracheal intubation has not been reported to occur in neurosurgical patients. Over a 1-year period, 11 patients admitted to the Intensive Care/Trauma Unit at St. Paul Ramsey Medical Center developed this entity. The mean age of these patients was 36 +/- 4 years; 7 were trauma victims, 3 had each had a subarachnoid hemorrhage, and 1 had suffered hypertensive hemorrhage. The patients presented with fever of unknown origin (FUO) and evidence of persistent hypermetabolism without an obvious cause. In 8 cases, the diagnosis was not suspected until mucopurulent nasal discharge was noted. Three additional cases were evaluated for suspected sinusitis before the occurrence of discharge. The mean duration of intubation before the diagnosis of sinusitis was 7.8 +/- 1.5 days. The diagnosis was confirmed by sinus films with a Waters view in 7 cases or by computed tomographic scanning in 4 cases and by bacteriological cultures. Two cases involved only the maxillary sinus on the side of intubation; the rest were polysinusites. The organisms involved included gram-positive and gram-negative species; all were polymicrobial with a single organism predominant. Secondary pulmonary involvement was common, and 4 patients revealed a bacteremia consistent with the major sinus organism. One patient developed septic shock. Treatment involved either orotracheal intubation or tracheostomy. This was curative in all cases. It is concluded that neurosurgical patients nasally intubated are at risk for sinusitis, which can have untoward effects such as septicemia or pulmonary infection. A high degree of suspicion will permit early diagnosis and treatment. PMID- 4033882 TI - An unusual spinal meningioma in a child: case report. AB - Meningiomas seldom occur in children, and spinal meningioma in a child is rare. We report the case of a boy, 3 years and 5 months of age, who had an unusual atypical meningioma involving the subarachnoid space from T-2 to the cauda equina. To our knowledge, no similar case has been reported previously. PMID- 4033883 TI - Spinal cord compression due to postoperative cervical pseudomeningocele. AB - A case of spinal cord compression due to postoperative cervical pseudomeningocele is reported. A 63-year-old man had undergone osteoplastic laminectomy of the C-3 through C-6 laminae for quadriplegia after a traffic accident 1 year and 4 months earlier. Computer-assisted tomography with metrizamide injection showed a pseudomeningocele in the paraspinous area at the C-3 through C-6 level. PMID- 4033884 TI - High altitude: an unusual cause of neurological deterioration in a patient with an arteriovenous malformation. AB - High altitude associated with neurological deterioration is an unusual presentation for an arteriovenous malformation (AVM). A case report of a man with a left temporal occipital AVM who developed symptoms that were markedly intensified by exposure to high altitude is presented. The AVM was removed surgically, and all symptoms resolved. The pathogenesis of this unusual AVM symptom complex is discussed in this report. PMID- 4033885 TI - Operative normalization of skull shape in sagittal synostosis. AB - The skull shape of most infants with sagittal synostosis can be normalized intraoperatively by combining sagittal strip, occipital circular, and parietal wedge craniectomies. The technique is associated with minimal morbidity. PMID- 4033886 TI - Subarachnoid hemorrhage due to a cerebral aneurysm at the anastomotic site between the frontoorbital artery and the anterior ethmoidal artery: a case report. PMID- 4033887 TI - Myelomeningocele occurring within a lumbosacral teratoma: case report. AB - The occurrence of a myelomeningocele completely embodied within a lumbosacral teratoma is extremely rare. We report on the clinical presentation, radiological appearance, surgical treatment, and histological make up of such a lesion. PMID- 4033888 TI - Giant aneurysm of an azygos anterior cerebral artery: report of two cases and review of the literature. AB - The authors present two cases of a largely thrombosed giant aneurysm of an azygos anterior cerebral artery. An aneurysm of an azygos artery is rare, and a giant aneurysm in this location is extremely rare. PMID- 4033889 TI - Lateral atlantooccipital dislocation: case report. AB - A case of lateral atlantooccipital dislocation is presented, and its successful management is outlined, demonstrating the importance of the physical examination and the utilization of computed tomography. Open reduction and stabilization with direct visualization of the spinal axis is the preferred method of treatment. PMID- 4033890 TI - Epidural hematoma and diffuse axonal injury. PMID- 4033891 TI - Microprolactinoma and large prolactinoma: are they two different diseases. PMID- 4033892 TI - Tension pneumocephalus. PMID- 4033894 TI - Recurrent course of primary affective disorders: explanation by the theory of biorhythms. AB - The authors present the classification of biorhythms from the cybernetic aspects. They utilize this approach in describing and explaining the clinical course of periodic diseases in general, and of primary affective disorders in particular. In more complex organisms there exists a great number of single subsystems and their interactions, and therefore more possibilities arise for the development of natural biorhythms. If the number of single subsystems is 'n', the number of possible interactions may reach the maximum value of 'n!'. In more simple organisms the pseudobiorhythms may develop. This study focuses on the relationship of proper biorhythms to the recurrent course of illness, especially to that of primary affective disorders (PAD). Based on Fourier's decomposition of the periodical course into single ones, the authors hypothetically explain the peculiarity of the periodic course of PAD. In addition to sine form courses, the recurrences may originate from superimpositions of courses which originate from nonlinearity of single subsystems and are not harmonic. In real biosystems, such courses are undoubtedly more frequent than purely harmonic courses. This observation does not contradict the applied mathematical model, because each of these nonharmonic periodical courses may be decomposed into the harmonic ones. The proposed hypothesis presents an alternative or a supplementary model to the prevailing hypothesis which explains the course of PAD by the desynchronization of circadian rhythms controlled by special biooscillators. PMID- 4033893 TI - Biochemical, physical and psychological findings in patients suffering from cardiac neurosis. AB - In 10 patients suffering from cardiac neurosis changes in plasma norepinephrine (NE) and epinephrine (E) were studied by an upright bicycle exercise and during psychological stress. Psychometric tests were also performed. 6 healthy subjects served as a control group. At exercise, no relevant differences in blood pressure and heart rate regulation between patients and controls were present. The NE and E increase was normal and similar in both groups. During psychological stress an equal plasma NE increase was seen in both groups. During recovery, however, a sustained release of NE was present in patients. It is concluded that patients with cardiac neurosis respond to psychological stress by an inappropriate sustained activation of the sympathetic nervous system. PMID- 4033895 TI - Clinical efficacy of drugs predicted from drug effects after short-term administration in animals, normal subjects and patients. PMID- 4033896 TI - Electroencephalographic Cartography. I. By means of mini- or microcomputers. Reliability and interest of this electrical non-invasive brain imagery. AB - We have recorded control subjects, neurological and psychiatric patients (n = 217 sequences recorded over both hemispheres). Minicomputers (HP Fourier analyzer, HP 1000) for spectral analysis provided 10 spectral parameters over 5 spectral frequency bands (delta, theta, alpha, beta 1, beta 2, raw EEG). For each recorded sequence, 90 EEG maps could be computed over both hemispheres. Topo-EEGs were stored in an EEG image data bank. An EEG mapping microcomputer system linked with a digital polygraph (Alvar Electronic, REEGA 2000) has been used simultaneously. White noises have been fed into both computers for testing spatial resolution. Ten topo-EEGs have been recorded in control subjects and patients. The microcomputer system has provided very reliable topographical results when compared to similar maps generated by the minicomputer. A common average reference has been used. First clinical applications have been studied (brain strokes, brain tumors). The method appears very reliable in comparison with CT scans. PMID- 4033897 TI - Psychiatric disorder in the parents of adopted children with aggressive conduct disorder. AB - The authors found that adoptive fathers of children with aggressive conduct disorder less often had alcoholism and antisocial personality than the natural fathers of nonadopted children with the same disorder. This evidence suggests that social factors which are widely held to produce the disorder are not necessary causes. PMID- 4033898 TI - Tobacco effects on cortical evoked potentials to distracting stimuli. AB - In a group of female smokers, cortical evoked potentials (EP) were averaged to low and high intensity auditory stimuli which were presented during both task and non-task conditions and in separate smoking and non-smoking sessions. Four individual EP peaks, P1,N1,P2,N2 and 3 peak-to-peak measures, P1-N2, N1-P2, N2 P2, were involved in amplitude analysis. Tobacco significantly interacted with intensity and task condition to produce both increases (P1, N1) and decreases (P2, P2-N2) in amplitudes of EP peaks. The results are discussed in relation to arousal and information processing. PMID- 4033899 TI - Delineation of pharmacopsychological effects by means of endogenous event-related brain potentials: an exemplification with flupentixol. AB - A new experimental paradigm for studying cognitive functions by means of endogenous event-related brain potentials is presented. The paradigm has the following characteristics: (1) subcomponents of 'P300' (P3a, P3b, positive slow wave) and subcomponents of 'CNV' (early and late wave) are separated in time; (2) probability effects known to work on P300 subcomponents are completely under experimental control; and (3) psychologically defined antecedent conditions which affect particular endogenous components can be manipulated precisely and independently of each other. The usefulness of the paradigm for monitoring pharmacopsychological effects on cognitive functions is exemplified by means of flupentixol (Fluanxol 0.5). Reliable drug effects were observed with a dosage of 2 mg/day after 4 days of treatment. The results can be taken as evidence that flupentixol has an impairing effect on human information processing resources; in particular functions related to motor preparation, perceptual analysis, and memory retrieval are affected. PMID- 4033900 TI - Sleep patterns of sober chronic alcoholics. AB - The somnopolygraphs of 26 sober chronic alcoholics were compared with those of an age-matched control group, after approximately 25 days of sobriety. The sleep efficiency index and latency to sleep onset were significantly disturbed in alcoholic subjects. There was a decrease in the number of REM episodes. Slow-wave sleep was unaffected except for an increase in the latency to stge 4 sleep. These findings are discussed in the light of previous research. PMID- 4033901 TI - Prefrontal cortex and the sequencing of movement in monkeys (Macaca mulatta). AB - There have been suggestions that the prefrontal cortex may play a role in the regulation of higher-order sequences of behaviour. In this experiment monkeys were taught a sequence of three movements. After removal of either sulcus principalis or the superior prefrontal convexity monkeys were able to perform the sequence normally. After removal of arcuate cortex (areas 8 and 6) monkeys were slow to learn the task; but it is argued that their impairment may not be one of sequencing per se. PMID- 4033902 TI - Gesture fluency after focal cortical lesions. AB - Patients with unilateral cortical excisions and normal control subjects were given two 'gesture fluency' tasks: one assessed their ability to generate novel finger positions, and the other their ability to produce meaningful gestures. Patients with left-frontal lesions were impaired on both tasks, and patients with right-frontal lesions were impaired on the latter. The deficit after right frontal lesions appeared to be associated with involvement of ventro-lateral or orbital cortex, whereas there was no evidence for localization within the left frontal lobe. The results extend previous findings of deficits after frontal lesions on tests of word and design fluency. PMID- 4033903 TI - Manual sequence learning after focal cortical lesions. AB - Patients with unilateral frontal or temporal excisions and normal control subjects learned sequences of hand positions. Left-frontal and left-temporal lesions impaired learning these sequences. No group had particular trouble when order of response was restricted to the original order, compared to when it was not restricted; nor were group differences seen when subjects learned new orders of already-familiar positions. Delayed recall of the positions (which had been learned to a common criterion), was not impaired in any group. Results suggested a role of the left-frontal and left-temporal lobes in learning series of manual responses. PMID- 4033904 TI - The effect of lesions of the corpus callosum on finger localization. AB - Finger localization was studied in 10 cases of cerebral commissurotomy (four complete, six partial) and 24 normal subjects. Stimulation of one finger with the same hand responding produced ceiling performance in all subjects. Responses with the other hand (cross-localization) were 82% worse with full commissurotomy, 28% worse with the trunk of the corpus callosum sectioned, and 7% worse in the controls. The trunk of the corpus callosum normally transfers tactile information, but the splenium can subsume 50% of this function and tactile transfer with complete commissurotomy exceeded chance levels. The partially sectioned and normal male subjects showed a right-hand stimulation advantage for sequences. In both normals and partially sectioned subjects, cross-localization was poorest when mirror-image transfer of finger sequences was required, while spatial alignment of the fingers facilitated transfer. With complete commissurotomy, response hand orientation did not affect cross-localization. Thus the corpus callosum transmits the position of each hand between the hemispheres. PMID- 4033905 TI - Hand and hemispace effects in tactual tasks in children. AB - In Experiment I, 3-and 5-yr-old dextrals matched textures better by either hand when it operated in left hemispace. Girls and 3-yr olds were the more disadvantaged by non-alignment of hand and hemispace. In Experiment II, 8-yr-olds reproduced finger sequences; dextrals demonstrated a right-hand and sinistrals a right-hemispace superiority. In Experiment III, both a left-hand and a left hemispace superiority appeared when 5-yr-old dextrals reproduced a static configuration of finger spacing. Asymmetries were generally stronger for the side of presentation than for the side of response. Our findings are consistent with the operation of two semi-independent systems, one involving hand-hemisphere connections, and the other mapping of extracorporeal space by the hemispheres. PMID- 4033906 TI - Early stages in the acquisition of a bimanual motor skill. AB - Children and adults were trained and tested on a coordinated bimanual task that required them to rotate both hands either at the same or at different angular velocities in order to move the pen of an X-Y recorder along three angles of slant (45, 67 and 22 degrees), and to rotate both hands in the same clockwise direction rather than as mirror image movements. Initially both groups exhibited a tendency to rotate both hands at the same angular velocity even when the task required differential motor output from the two hands. With visual feedback, the tendency toward synchronization, such that both hands moved at the same angular velocity, was asymmetrically distributed, but under blindfolded conditions such asymmetries disappeared. Accuracy of performance increased with practice; and visual feedback enhanced accuracy of performance. The findings suggest that during early stages in the acquisition of a bimanual skill, unintended bilateral coactivation occurs at multiple levels of motor organization; mirror associated movements are only one simple subset of unintentional intermanual synergies. PMID- 4033907 TI - Dichotic listening tests in studying brain-behavior relationships. AB - The magnitude of perceptual asymmetry (PA) on a CVC fused dichotic words test and on VCV and CV fused nonsense syllables tests were compared. In each test the set of distinguishing phonemic cues was the same; the six English stop consonants, b,p,d,t,g,k. Although test-retest reliability was very high on all three tests there was no correlation across individuals between the degrees of PA on different tests. Moreover, the magnitude of PA on the VCV nonsense test increased as field dependence (FD) increased on the field dependence index (FDI) of the WAIS while there was no relationship between FD and the magnitude of PA on the CVC words test. In addition, concurrent visual tasks increased PA on the VCV nonsense test and decreased it on the words test. In order to facilitate the use of such data, Kimura's classical model of the physiological basis of PA is modified by including components of primary receptive and secondary and tertiary associative function. Comparison of highly similar PA measures, that differ in specific ways, is discussed as a means of collecting data for mapping cerebral functional space and exploring brain-behavior relationships. PMID- 4033908 TI - Styles of mental imagery in blind adults. AB - Two tests of mental imagery were administered to six blind and four sighted subjects. One test, involving pictorial imagery, required subjects to imagine a checkerboard of which only certain squares, specified by the experimenter, were filled in; the other test was similar but emphasized nonpictorial imagery, requiring subjects to imagine a three-dimensional assemblage of small cubes. In both cases, the subject's task was to name a common object which the imaged pattern resembled. It was found that the greater the proportion of life for which each of the blind subjects had been without sight, the less was his or her pictorial score, expressed as a proportion of total imagery score. This suggests that the nature of mental imagery slowly changes following the loss of sight. Relative facility with the two types of imagery also varied from one subject to another within the sighted group; hand movements used by some of them as an aid to imagery may have been a factor in producing this variation. PMID- 4033909 TI - Visual laterality effects and cerebral speech dominance determined by the carotid Amytal test. AB - Epileptic patients whose speech dominance had been ascertained using the carotid Amytal test were given a verbal-visual half-field task. Patients with left hemisphere speech dominance, like normal controls, tended to show a RVF effect whereas patients with atypical speech patterns showed a bias in favor of the LVF. PMID- 4033910 TI - Paralexic errors in Broca's and Wernicke's aphasia. AB - Paralexic speech errors were examined during the oral reading of sentences for 12 right-handed adults, including four Broca's aphasics, four Wernicke's aphasics and four patients with unilateral right-hemisphere lesions. A category system of error types was developed, and 129 errors were analyzed in terms of identifiable linguistic components, operating in isolation as well as interactively. The two aphasic groups produced a variety of errors, whereas the right-hemisphere group produced very few in number and type. Broca's aphasics committed more morphological errors than did Wernicke's aphasics, whereas Wernicke's aphasics committed more graphophonemic-neologistic errors than did Broca's. PMID- 4033911 TI - Functional inhibition and release: unilateral tachistoscopic performance and stereoelectroencephalographic activity in a case with left limbic status epilepticus. AB - During prolonged nonconvulsive unilateral left limbic status epilepticus, a natural model of functional hemispheric inhibition, we performed two tachistoscopic experiments, a lexical decision task associated with a RVF (left hemisphere) superiority and a facial matching task associated with a LVF (right hemisphere) superiority. We found that epileptic activity in the left hemisphere, especially rhythmic high-frequency "tonic" discharges, inhibited performance on the lexical task but not on the facial matching task. This suggests that only cognitive activity in the discharging hemisphere is inhibited. Strikingly, the best performance of the right hemisphere was obtained while the left hemisphere was most inhibited, suggesting a functional balance of inhibition and release. PMID- 4033912 TI - Projections of the amygdala to striopallidal formations in cats. PMID- 4033913 TI - Changes in structural heterogeneity of surviving nerve cells. PMID- 4033914 TI - Changes in dendrites in chronic morphine intoxication. PMID- 4033915 TI - Participation of the lateral geniculate body in mechanisms of brain activation. AB - The significance of the lateral geniculate body for nonspecific activation of the brain was elucidated in experiments on cats. It was established that when the connections of the lateral geniculate body remain intact, its stimulation elicits the usual activation of the EEG, but at higher threshold values of the current (120-190 microA) than when the mesencephalic reticular formation of the medial center of the thalamus is stimulated (50-80 microA). If only direct connections with the cortex remain, however, and the others are disrupted, the threshold for activation increases to 220-400 microA. When the lateral geniculate body is coagulated, cortical activity occurs only in response to very bright light flashes (250-1000 1x). All of this indicates that, in addition to carrying out its principal function of processing and sending the basic flow of visual impulsation to higher optical centers, the lateral geniculate body may be the source of activating transmissions sent to the cortex. Nonspecific stimulation that develops in the cortex is subsequently regulated by the cortex itself; the cortex plays a leading role in these processes. PMID- 4033916 TI - Convergence and interaction of somatic and visceral impulsation on neurons of the ventral posterolateral thalamic nucleus. AB - Acute experiments on anesthetized and immobilized cats using extracellular derivation of neuronal responses and field potentials demonstrated the predominant localization of somatic (radial nerve) responses in the mediocentral and of visceral (splanchnic nerve) responses in the centrolateral regions of the ventral posterolateral thalamic nucleus. Both similarities and differences were found in patterns of neuronal responses to peripheral stimuli of different types. A quite high degree of convergence of somato-visceral impulsation was found in the central part of the nucleus compared with its medial and lateral regions. Predominance of comparatively long-latency convergent neurons over short-latency was observed. The inhibitory character of somatovisceral interaction and the more effective inhibitory influence of conditioning stimulation of the radial nerve on test-response of splanchnic origin were demonstrated. PMID- 4033917 TI - Changes in neocortical function in response to the direct action of optical radiation. AB - The action of optical radiation on neocortical bioelectrical activity and on a penicillin-induced epileptic focus was investigated. The direct action of ultraviolet (UV) radiation with wavelengths 280, 310, and 365 nm was shown to increase the amplitude of the spontaneous EEG and to potentiate epileptiform activity, whereas the action of subthreshold radiation with wavelengths of 580 and 630 nm caused a reduction of EEG amplitude and inhibition of epileptiform activity. On the basis of the writers' own results and data in the literature it is postulated that the mechanism of action of UV radiation on neocortical electrical activity is based on changes in permeability of neuronal membranes to Na and K ions and subsequent membrane depolarization, whereas the action of visible radiation leads to thermal injury to the neurons in the irradiated zone, inducing irreversible suppression of their activity and a decrease in amplitude of the EEG. PMID- 4033918 TI - Effects of intracortical microstimulation on the activity of limb muscles in alert rabbits. AB - Motor and EMG responses of the limbs to intracortical microstimulation (IM) were studied in 14 rabbits. The motor representations (MR) of contralateral limbs are separately located in the neocortex. The zone of wrist control lies in the center the MR of the forepaw, surrounded by the zones of the forearm and shoulder. Efforts to obtain isolated responses of the digits to IM were not successful. We did not observe a geometrical pattern of organization in the more caudally placed MR of the hindleg, where IM elicited isolated responses in the muscles of the lower leg and the haunch. Minimal thresholds of IM reached 3-10 microA for the MR of the shoulder and forearm, but were as high as 30-200 microA in the MR of the haunch and lower leg. The latent periods of the EMG responses lasted 25-52 msec for the shoulder, 24-73 msec for the forearm, 32-54 msec for the haunch, and 36 71 msec for the lower leg. We conclude that the organization involved in the cortical regulation of limb movement in rabbits is primitive, especially where movement of the hindlimb is involved. PMID- 4033919 TI - Intracentral connections of the brain structures participating in the regulation of blood flow. AB - In this study, we conducted an investigation into the characteristics of hemodynamic reactions during electrical stimulation of the structures of the hypothalamus and during simultaneous stimulation of the sinus nerve and the hypothalamus in anesthetized cats. We also investigated the monosynaptic connections of the hypothalamus with the structures of the brain stem and spinal cord. The possible influence of the hypothalamus, following the activation of various descending pathways (both through the bulbar level of regulation and by passing it), upon the efferent component of the regulation of blood circulation is discussed; a scheme of intracentral connections of the brain structures participating in the regulation of blood circulation is presented. PMID- 4033920 TI - Spectral analysis of the EEG in neuronally isolated cortex of the rabbit brain. PMID- 4033921 TI - Impulse activity of medulla oblongata in rats in response to stimulation of taste receptors and visceral chemoreceptors. AB - We have recorded extracellularly the impulse activity of the rat medulla oblongata during stimulation of taste receptors of the tongue and visceral chemoreceptors with solutions of hydrochloric acid and sodium chloride. We have detected in the caudal region of the nucleus of the solitary tract, neurons that react to the chemical stimulation of either one or both the receptive zones mentioned. The response reactions of the isolated groups of units (taste, viscerochemical, and convergent neurons) are tonic and are characterized by a high level of impulse activity. We have established that the neurons of each of the groups isolated are capable of discriminating between salt and acid solutions. Using the example of sodium chloride solutions we have shown that an increase in the number of viscerochemical neurons which inhibit their own background activity on increase in the concentration of any substance in the intestine is an important index of the satiation of an animal and can serve as a starting link in the mechanism of food rejection. PMID- 4033922 TI - Influence of stimulation of the head of the caudate nucleus on the activity of postural muscles during realization of an instrumental defensive reflex. AB - A model of instrumental defensive reflexes associated with the maintenance of a specific posture was used in chronic experiments with four dogs to demonstrate the preferential inhibitory influence of preliminary low-frequency stimulation (2 impulses/sec) of the head of the caudate nucleus in the right and left hemispheres on the electromyographic and mechanographic components of the instrumental defensive reflex effecting the reflex motor program. Subjected to the greatest changes were the postural components of the electromyogram, which permits the postulate as to the importance of the caudate head in the organization of posture. It was shown that the caudate head is bilaterally involved in the prerelease processes preceeding the instrumental response. At the same time, the difficulty of inhibiting the performance of the actual instrumental task - the avoidance of an electric current - was noted during stimulation of the caudate head in a system of instrumental defensive reflexes. PMID- 4033924 TI - Alterations of regional cerebral blood flow and oxygen metabolism in Parkinson's disease. AB - Regional cerebral blood flow (rCBF) and oxygen metabolism (rCMRO2) were determined in six normals, six unilateral Parkinson's disease (PD) patients, and eight bilateral PD patients. In the unilateral patients, rCBF and rCMRO2 in the basal ganglia contralateral to the symptomatic limbs was 13% higher than on the other side (p less than 0.01); in the frontal cortex it was 8% lower than the other side, suggesting abnormal neuronal function in both regions. The bilateral PD patients had a widespread decrease (20%) in rCBF unaccompanied by comparable changes in rCMRO2, suggesting vasoconstriction due to loss of dopaminergic innervation of blood vessels in more advanced PD patients. PMID- 4033923 TI - Electrical phenomena in the telencephalon of the pigeon during pecking. AB - So-called motor potentials and changes in the neuronal activity of various regions of the striatum during pecking were studied in 50 unrestrained pigeons. The motor potentials which appeared during pecking were recorded from all regions of the striatum. Neurons of the striatum changed their level of activity during pecking (they became more active for the most part). The temporal characteristics of the motor potentials and the neuronal activity suggest a rostro-caudal activation of the striatum. The amplitude of the evoked potential of the tectum in response to a flash of a light changed during pecking movements. PMID- 4033925 TI - Laminar organization of cholinergic circuits in human frontal cortex in Alzheimer's disease and aging. AB - Cholinergic enzyme activity (choline acetyltransferase, CAT; acetylcholinesterase, AChE) and muscarinic cholinergic receptor density were measured in frontal cortex (Brodmann's area 9) of normal patients over the life span and in brains of patients with Alzheimer's disease (AD). CAT, but not AChE activity, declined with normal aging. Significant loss of CAT and AChE activity occurred in the AD brains, but later onset AD was associated with less severe loss of frontal cortex CAT activity. The majority of normal CAT activity resided in lamina I, II, and upper lamina III; CAT loss in AD resulted in large losses from all depths, most notably the upper cortical layers. AChE did not precisely correspond to the localization of CAT; loss of AChE in AD was consistent across all six laminae. No differences were seen in muscarinic cholinergic receptor binding between AD and age-matched controls; the distribution of binding was equal in all layers of normal frontal cortex, and no laminar differences were detected in distribution of cholinergic receptors between normal and AD samples. PMID- 4033926 TI - Optic nerve demyelination induced by human serum: patients with multiple sclerosis or optic neuritis and normal subjects. AB - We injected guinea pig optic nerves with serum from patients with MS or acute optic neuritis (ON), or normal subjects. Serum from 12 of 17 MS patients, 3 of 3 patients with ON, and 5 of 11 normal age- and sex-matched controls produced myelin vesiculation and demyelination 24 hours after injection. Nerves injected with demyelinating serum contained oligodendrocytes with pyknotic nuclei and edematous, rarefied cytoplasm. Nerves injected with serum that did not cause demyelination did not have these oligodendrocyte changes. Serum from normal subjects or patients with MS may induce in vivo demyelination in mammalian CNS. PMID- 4033927 TI - Visual evoked potentials by different check sizes in patients with multiple sclerosis. AB - Visual evoked potentials (VEPs) were obtained using three checks of different size (25', 50', and 100' of arc) in 20 normal controls and 1,006 patients. The test was abnormal in 270 patients regardless of the check size, whereas in 53 patients, a prolongation of P100 latency occurred only with checks of a certain size. The procedure was most sensitive in detecting abnormalities with combined application of 25' and 100' checks and least sensitive with the 50' checks alone. In occasional subjects showing W-shaped responses, the use of another check size often elicited the usual V-shaped pattern, alleviating the problem of selecting the peak for latency determination. PMID- 4033928 TI - Chronic encephalitis possibly due to herpes simplex virus: two cases. AB - Two patients had clinical findings of encephalopathy that progressed in 4 to 5 months. One patient had headache, fatigue, lethargy, hemiparesis, and a seizure. The second patient had only forgetfulness, confusion, and lethargy without focal signs. Herpes simplex virus was grown from brain biopsy in the first patient and from CSF in the second patient. These cases suggest that herpes simplex virus caused the encephalitis and that it should be considered in the differential diagnosis of chronic encephalopathy. PMID- 4033929 TI - Central nervous system toxicity with high-dose Ara-C. AB - We evaluated the CNS complications in 118 adults with acute leukemia who received IV high-dose Ara-C therapy. Fourteen (12%) had cerebellar signs, encephalopathy, seizures, or leukoencephalopathy. Symptoms usually occurred within 24 hours after the last treatment. Patients receiving a cumulative dose in excess of 24 g/m2 had more severe or irreversible symptoms. After lower cumulative doses, symptoms often resolved even though treatment was continued. The incidence of CNS complications of high-dose Ara-C is acceptable and is potentially reversible if appropriate precautions are taken. PMID- 4033930 TI - Respiratory epithelial cells masquerading as agents of primary amebic meningoencephalitis: distinguishing features. AB - CSF does not normally contain motile cells within flagella or cilia. When motile cells are seen in the CSF, they may be incorrectly assumed to be amebae. We studied a patient with a traumatic mucocele, in whom motile ciliated respiratory epithelial cells were seen in the CSF and within a frontal lobe brain abscess. PMID- 4033931 TI - Time course of a single oral dose of propranolol in essential tremor. AB - We studied the effects of a single oral dose (120 mg) of propranolol on essential tremor in 12 patients. Postural hand tremor was recorded by an accelerometer, and its amplitude and frequency determined by spectral analysis. Variable patterns of individual responses gave a mean reduction of tremor amplitude of 50% at 2 hours. Tremor was suppressed as long as 8 hours in some patients. Similar tremor reduction was found on chronic therapy. Even without treatment, tremor amplitude varied from 30 to 50%. A single oral dose of propranolol produces a rapid and sustained reduction of essential tremor, but there are diurnal fluctuations of tremor intensity regardless of treatment. PMID- 4033932 TI - Blepharospasm, Meige syndrome, and hemifacial spasm: treatment with botulinum toxin. AB - In 34 patients with idiopathic blepharospasm, 5 with Meige syndrome, and 11 with hemifacial spasm, local injection of botulinum toxin gave temporary relief from the involuntary movements of the eyelids. Local ophthalmologic side effects were minimal. There are no known systemic side effects. The procedure had to be repeated every 12 weeks. Tolerance to the toxin did not appear. PMID- 4033933 TI - Cerebral infarct in apparent transient ischemic attack. AB - Fifty-seven patients with transient ischemic attacks in the carotid territory had CTs 3 to 28 days after the last episode. Sixteen (28%) showed an infarct appropriate to the symptoms. Infarcts were more likely with longer mean duration of attacks, longer duration of the longest attack, longer total duration of symptoms, and smaller number of attacks. Age, sex, type and extent of hemisphere symptoms, and vascular risk factors had no influence. If attacks lasted more than 45 to 60 minutes, the risk of infarction was more than 80%; most were actually infarcts. So-called TIAs included two subgroups, true TIA and CITS (cerebral infarction with transient signs), which corresponded respectively to a short (mean, 21 minutes) or long (mean, 6 hours) duration of attack. PMID- 4033934 TI - Arrhythmogenic seizures: diagnosis by simultaneous EEG/ECG recording. AB - We studied a young man with presumably idiopathic seizures that were refractory to phenytoin therapy. Sick sinus syndrome was found after an episode of unconsciousness, but seizures continued despite the insertion of a demand ventricular pacemaker. Evaluation revealed a left temporal seizure focus, and combined EEG and ECG monitoring during a seizure revealed a left temporal paroxysmal discharge and an ictal cardiac arrhythmia. Detailed EEG and cardiac evaluation is necessary for all patients with "idiopathic" seizures. PMID- 4033935 TI - Neurologic symptoms of biotinidase deficiency: possible explanation. AB - We found that the activity of biotinidase is much lower in human and rat brain or human CSF than in serum or other tissues that have biotin-dependent carboxylase activity. The brain seems to be unable to recycle biotin and depends on biotin transferred across the blood-brain barrier. The biotin-deficient state that results from an inherited lack of biotinidase results in a moderate decrease in brain pyruvate carboxylase activity. This is followed by more severe accumulation of lactate in brain than in other organs, which may explain why affected children have neurologic symptoms before many peripheral features. PMID- 4033936 TI - Adrenoleukodystrophy: abnormality of "tightly bound" fatty acids in the erythrocyte membrane proteins. AB - "Tightly bound" and "loosely bound" fatty acids in erythrocyte membranes were analyzed in three patients with adrenoleukodystrophy, three probable carriers, and eight controls. The ratios of C28:0 or C26:0 to C22:0 or C20:0 in the tightly bound fatty acids of three patients were significantly higher than those of controls, and the ratios in two of three probable carriers were higher than those in controls. The ratios of C26:0 to C22:0 or C20:0 in the loosely bound fatty acids of three patients and three probable carriers were also significantly higher than those of controls. Since tightly bound fatty acids in membrane proteins are found not only in erythrocyte membranes but also in myelin proteins, the abnormality of tightly bound fatty acids may be related to the demyelination in adrenoleukodystrophy. PMID- 4033938 TI - Syndrome of diffuse encephalopathy due to nondominant thalamic infarction. AB - A 69-year-old woman suddenly became comatose. Within 24 hours, she became lethargic, with a diffuse encephalopathy and no focal neurologic abnormalities. CT revealed a large, nondominant thalamic infarct. PMID- 4033937 TI - Duchenne muscular dystrophy: normal ATP turnover in cultured cells. AB - We examined ATP metabolism in cultured muscle cells and fibroblasts from patients with Duchenne dystrophy. ATP and ADP levels were the same in cultured cells from normal subjects and patients, and there was no difference in ATP synthesis or degradation. Although there was a significant decrease in radioactively labeled ATP after incubation with deoxyglucose in Duchenne muscle cells, there was no difference in ATP concentration or ADP metabolism. PMID- 4033939 TI - Manifestations of pontine hemorrhage. PMID- 4033940 TI - Epidemiological studies on multiple sclerosis. PMID- 4033941 TI - Estimating physician requirements for neurology. PMID- 4033942 TI - Head injury and Alzheimer's disease. PMID- 4033943 TI - Head trauma and seizures as risk factors in tumors of the glioma group. PMID- 4033944 TI - Oligoclonal bands in multiple sclerosis: an index of disease activity? PMID- 4033945 TI - Bilateral cerebellar infarction in the distribution of the superior cerebellar artery. PMID- 4033947 TI - Erythromycin intravenous management in neurosyphilis. PMID- 4033946 TI - Hypothyroidism with a "normal thyroid panel". PMID- 4033948 TI - Myotonic dystrophy and normal-pressure hydrocephalus. PMID- 4033949 TI - Effect of fatty acid-enriched diet on the composition of fatty acids in lipids of cerebral myelin during development. PMID- 4033950 TI - Influence of inappropriate diet during development on the susceptibility to experimental allergic encephalomyelitis. PMID- 4033951 TI - [Identification of dopaminergic vesicles in the electron-microscopic picture of the compact layer of the substantia nigra in the rat]. PMID- 4033952 TI - Diagnostic value of demonstrating glial fibrillary acidic protein in human astrocytomas. PMID- 4033953 TI - [Diagnostic value of demonstrating glial fibrillary acidic protein in ependymomas]. PMID- 4033954 TI - [A case of carcinomatosis of the pia mater]. PMID- 4033955 TI - Effect of high ambient temperature on the hypothalamo-neurohypophysial system of the rabbit. I. The supraoptic and paraventricular nuclei. PMID- 4033956 TI - Effect of high ambient temperature on the hypothalamo-neurohypophysial system of the rabbit. II. The neurohypophysial axons. PMID- 4033957 TI - [Morphological changes and acid phosphatase and thiamine pyrophosphatase activities of the nuclei of the reticular formation and neurosecretory nuclei of the hypothalamus in rabbits exposed to increased environmental temperature]. PMID- 4033959 TI - Trends in pituitary surgery. PMID- 4033960 TI - Role of cell and explant culture in the diagnosis and characterization of human pituitary tumours. AB - The pattern of hormone secretion by human pituitary tumours in cell or explant culture has been shown to be of value in establishing the nature of the tissue. There was complete agreement between the diagnosis reached by conventional immunocytochemical techniques and by examining the secretion of hormones in culture. Culture techniques, however, have some advantages over immunocytochemical analysis. In particular, immunocytochemical techniques can only be used to examine a small, possibly unrepresentative, portion of the pituitary tissue, whereas the in vitro culture systems make use of the whole tissue. In addition, in vitro culture is simpler to employ and can be carried out relatively rapidly. Cell and explant culture was therefore used to examine the nature of human pituitary tumours. To determine the incidence of mixed GH-PRL secreting pituitary tumours in acromegaly, the pattern of hormone secretion in vitro by 98 somatotrophic tumours was examined. Thirty-seven per cent were found to be pure somatotrophic tumours and 59.2% secreted both GH and PRL, but no other hormone, indicating that these tumours were of mixed nature. This latter group could be divided into those removed from patients with hyperprolactinaemia (35.7% of all tumours) and those from patients with normal pre-operative serum PRL levels (23.5%). A further small group (3.1%) of tumours secreted only GH in culture, despite elevated pre-operative serum PRL levels, indicating that the hyperprolactinaemia in these patients was due to pituitary stalk compression by the somatotrophic tumour, thereby preventing prolactin release inhibiting factor reaching the lactotrophs and allowing uncontrolled PRL secretion.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4033961 TI - Nuclear magnetic resonance imaging of the region of the sella turcica. AB - Nuclear magnetic resonance (NMR) imaging is a versatile technique which has proved more sensitive in the detection of perisellar lesions than CT. A multiplanar facility, the demonstration of blood flow, and the lack of bone artefacts are its main advantages in this respect. Limitations are seen in its inability to identify small calcifications and to distinguish clearly perifocal oedema and tumour especially in malignant lesions. Relatively thick slices of 5 10 mm make the detection of microadenomas very difficult, mainly because of partial volume effects. T1 and T2 values alone are not sufficient to provide specific diagnosis. No reliable criteria have been determined yet, which would indicate the quality of pathological involvement of peritumorous structures by tumours of the sella region. At present NMR still plays a more complementary role to CT in the evaluation of this complex anatomical area. We are confident that with future technical refinements NMR will be able to replace ionizing radiation for the diagnostic imaging of the sella. PMID- 4033958 TI - Hypophyseal region--anatomy of the operative approaches. AB - Landmarks and measurements for the transnasal approach (apertura piriformis, distance to the apertura sinus sphenoidalis) in children and adults are given. Included is the anatomy of the nasal septum, its vessels and nerves. The ostium of the sphenoid sinus, its development, types and dimensions are described. Also shown are the hypophyseal capsule, the hypophyseal vessels and the hypophyseal fossa with its variations and the sella turcica region with its adjacent dural structures (petroclinoid fold, diaphragma sellae, aperture for the internal carotid artery and pituitary cistern). For the intracranial approaches the arterial circle and its branches are important for neurosurgeons. The location, number, width and course of these branches are described. Distances and the most important vessels, which are seen by frontal, frontolateral and pterional approaches, are described. PMID- 4033962 TI - Recurrent pituitary adenomas. AB - Based on 880 pituitary adenomas operated upon between 1972 and 1982 the diagnostic and therapeutical strategy in recurrences is discussed. The incidence of reoperations was 7.75%, 3.7% in hormonally inactive and 4.1% in hormonally active recurrences. The rate was 30% after transcranial surgery--due to the extension of the tumours--and 5% after the trans-sphenoidal approach. In hormone inactive adenomas visual impairment in 29 out of 50 recurrences caused a second operation combined with radiotherapy in 13 cases. Radiotherapy alone was used in 17 cases. In hormonally active adenomas the treatment of persistent hormonal excess represents the main therapeutical problem. With HGH-producing adenomas a return to normal was achieved in 22 cases mainly by a combination of reoperation and radiotherapy (12) or radiotherapy (8) alone. Radiotherapy should be avoided in young patients whenever possible. The procedure of choice in PRL-producing adenomas (14 cases) seems to be treatment with dopamine-agonists (9). An additional reoperation was necessary in five cases. PMID- 4033963 TI - [The electrocardiogram in the diagnosis of infarct of the right ventricle]. PMID- 4033964 TI - [Neurovegetative manifestations: duodenal ulcer and myocardial infarct]. PMID- 4033965 TI - [A case of atrial disassociation caused by complete intra-atrial block with problems in the differential diagnosis in relation to atrial parasystole]. PMID- 4033966 TI - [Monitoring of anti-arrhythmia drugs with the Holter system and the determination of their blood levels (mexiletine (mexitil) and amiodarone)]. PMID- 4033967 TI - [Pacemaker implants in patients with pathology of the carotid axis]. PMID- 4033968 TI - [Ventricular fibrillation in the course of Sheehan's syndrome. Description of a case]. PMID- 4033969 TI - [Platelet activation in thrombotic and prethrombotic venous pathology]. PMID- 4033970 TI - [Non-invasive evaluation of myocardial function in patients undergoing aorto bifemoral bypass]. PMID- 4033971 TI - [Preclinical changes of left ventricular function in chronic alcoholics. Study with non-invasive methods]. PMID- 4033972 TI - [2 cases of combined aorto-femoral and femoral-popliteal arterial reconstruction]. PMID- 4033973 TI - [Reliability of thromboendoarteriectomy in aorto-iliac obstructions]. PMID- 4033974 TI - [A case of retroperitoneal fibrosis simulating ruptured abdominal aorta aneurysm in computed axial tomography]. PMID- 4033975 TI - [A technic of ascending-descending aorta bypass in the treatment of aortic coarctation in the adult. Description of 7 cases]. PMID- 4033976 TI - [Total gastrectomy in the surgical therapy of neoplasms of the stomach]. PMID- 4033977 TI - [Surgical treatment of gastro-esophageal reflux caused by hiatal hernia. II: Results and discussion]. PMID- 4033978 TI - [Preoperative preparation in elective recto-colonic surgery. Our experience]. PMID- 4033979 TI - [Indications for internal, lateral and posterior sphincterotomy in proctologic surgery]. PMID- 4033980 TI - [Our experience in the diagnosis and surgical therapy of calculi of the choledochus]. PMID- 4033981 TI - [Review of 50 cases of choledochoduodenostomy]. PMID- 4033982 TI - [Results of clinical examinations in cholecystectomized patients]. PMID- 4033983 TI - [Role of hepato-biliary scintigraphy (99mTc-IDA) in the diagnosis of obstructive jaundice]. PMID- 4033984 TI - [Popliteal entrapment syndrome]. PMID- 4033985 TI - [Acute traumatic arterial lesions]. PMID- 4033986 TI - [Palliative operations in the post-thrombotic syndrome]. PMID- 4033987 TI - [Intra-operative cholangiography: systematic or selective?]. PMID- 4033988 TI - [A useful semiologic sign as evidence of free air in the abdomen]. PMID- 4033989 TI - [5 years results of surgery of stage I and II cancer of the lung]. PMID- 4033991 TI - [Potentials and limitations of surgical therapy of complete obstruction of the internal carotid]. PMID- 4033990 TI - [Significance and limitations of intensive follow-up after radical intervention for colorectal cancer]. PMID- 4033992 TI - [A case of a complicated arteriovenous fistula]. PMID- 4033993 TI - [A new membrane oxygenator: Capiox II. Comparative evaluation with a bubble oxygenator]. PMID- 4033994 TI - [Leiomyosarcoma of the esophagus. Description of a case and review of the literature]. PMID- 4033995 TI - [Malignant neoplasms of the small intestine]. PMID- 4033996 TI - [Traumatic injuries of the caudate lobe. Notes on embryology, anatomy and physiopathology, Presentation of a clinical case]. PMID- 4033997 TI - [Carcinoma of the gallbladder]. PMID- 4033998 TI - [Surgical treatment of gastro-esophageal reflux in hiatal hernia. I. Proposal for a technical modification of the Lortat-Jacob intervention]. PMID- 4033999 TI - [Tumors of the small intestine]. PMID- 4034000 TI - [Neoplasms of the colon. Presentation of 122 cases observed between 1975 and 1983]. PMID- 4034001 TI - [Intrathoracic malignant schwannoma. Apropos of a case]. PMID- 4034002 TI - [Mastectomy and breast reconstruction: surgical therapy of cancer of the breast as a function of current reconstructive demands]. PMID- 4034003 TI - [Mastectomy and breast reconstruction: selection criteria of candidates for breast reconstruction]. PMID- 4034004 TI - [Mastectomy and breast reconstruction: possibilities and limitations of post mastectomy reconstructive surgery]. PMID- 4034005 TI - [Round table on: Melanoma: problems of therapy]. PMID- 4034006 TI - [Diagnostic validity of needle aspiration cytology in breast nodules]. PMID- 4034007 TI - [Blood gastrin in childhood]. PMID- 4034009 TI - [Value of laser treatment in tracheal stenosis of surgical significance]. PMID- 4034008 TI - [Papillary carcinoma of the thyroid. Analysis of survival in 186 cases]. PMID- 4034010 TI - [Treatment of the perineal wound after abdomino-perineal amputation of the rectum]. PMID- 4034011 TI - [Acute celiac-mesenteric insufficiency]. PMID- 4034012 TI - [Hiatal hernia as a complication of Heller's operation]. PMID- 4034013 TI - [Traumatic lesions of the rectum. Apropos of 6 cases]. PMID- 4034014 TI - [Bilirubin conjugates in the bile obtained by ERCP and the effect of glucagon on their composition]. PMID- 4034015 TI - [Gastric emptying in patients with duodenal peptic ulcer before and after H2 blockader therapy]. PMID- 4034016 TI - [Gastrointestinal hormones in chronic atrophic gastritis]. PMID- 4034017 TI - [Gastroesophageal reflux after gastric resection]. PMID- 4034019 TI - [Role and indications of manometry and Ph-metry in the pathology of the esophagus and esophagogastric junction]. PMID- 4034018 TI - [Follow-up in erosive hemorrhagic duodenum. Evaluation of the risk of duodenal ulcer]. PMID- 4034020 TI - [Relations between endoscopic and histological aspects of superficial gastritis, atrophic gastritis and gastric atrophy in aged patients]. PMID- 4034021 TI - [Precancerous conditions of the stomach and gastric cancer: search for a correlation]. PMID- 4034022 TI - [Ulcerative colitis and Crohn disease. Clinical and developmental aspects]. PMID- 4034023 TI - [Hepatic encephalopathy after portacaval anastomosis. Retrospective analysis of its occurrence at the clinical and subclinical level]. PMID- 4034024 TI - [Comparison of radiography and endoscopy in the diagnosis of neoplasms of the large intestine]. PMID- 4034025 TI - [Gastric polyps. Diagnostic and therapeutic considerations]. PMID- 4034026 TI - [Role of esophageal manometry in the diagnosis and developmental control of scleroderma]. PMID- 4034028 TI - [Endoscopy in ulcerated carcinoma of the stomach and differential diagnostic and prognostic considerations]. PMID- 4034027 TI - [Endoscopy in the differential diagnosis of peptic and neoplastic ulcer of the stomach]. PMID- 4034029 TI - [Statistical evaluation of polyps of the large intestine]. PMID- 4034030 TI - [Gastric cancer and duodenal ulcer. Our observations]. PMID- 4034031 TI - [Treatment of perforated duodenal ulcer in post-cimetidine era]. PMID- 4034032 TI - [Ranitidine and cimetidine in the treatment of duodenal ulcer. Comparison after 3 and 6 weeks]. PMID- 4034033 TI - [Comparison of cimetidine and antacids in short-term and long-term therapy of duodenal ulcer]. PMID- 4034034 TI - [Behavior modification in the treatment of chronic constipation]. PMID- 4034035 TI - [New trends in the treatment of gastrinoma]. PMID- 4034036 TI - [Hemorrhagic colitis caused by antibiotic therapy]. PMID- 4034037 TI - [Nylon-thread drainage and slow section with elastic band in the treatment of perianal fistulas with sphincter involvement]. PMID- 4034038 TI - [Drainage in abdominal surgery]. PMID- 4034039 TI - [Turcot's syndrome. Report of a case of familial diffuse polyposis associated with cerebral tumor]. PMID- 4034040 TI - [A rare complication of esophagogastroduodenoscopy]. PMID- 4034041 TI - [Pseudomembranous colitis induced by clindamycin-lincomycin combination. Description of a clinical case]. PMID- 4034042 TI - [Dietary factors and breast carcinoma. Epidemiological aspects]. PMID- 4034043 TI - [Ischemic heart disease. Value, in the diagnosis, prognosis and selection for therapy, of angiocardioscintigraphy and myocardial scintigraphy]. AB - Prevailing must be referred to the radioisotopic methods in the diagnosis of the ischemic heart disease. Alterations of coronary artery disease with first pass and multiple gated equilibrium cardiac blood pool scintigraphy and myocardial scintigraphy are described. The importance of such data--particularly if obtained under stress--are noticed and also its usefulness at the prognostic aims, for the decision between medical or surgical therapy. PMID- 4034044 TI - [Arteriosclerosis and aneurysms of the abdominal aorta]. AB - To substantiate the hypothesis of a non atherosclerotic origin of abdominal aortic aneurysms, the author compares 40 patients operated on for abdominal aneurysm vs 50 patients operated on for atherosclerotic aorto-iliac occlusive disease at the 1st Surgical Clinic of the University of Cagliari. The mean age of the aneurysm patients was greater than that of the patients with occlusive disease and symptoms of arterial insufficiency of the lower limbs were uncommon. The more statistically significant feature was the difference in the site of lesions: in the aneurysm group, in fact, iliac arteries were uninvolved in 30% of patients, while in the occlusive group lesion involved the iliac tree in all but one case. Furthermore the majority of aneurysm patients showed an undamaged distal vascular bed, in sharp contrast with the occlusive group. Despite of these differences, however, the present series is too small to allow firm conclusions: in consideration of the equality of associate diseases and of lipoprotein patterns between the two groups of patients, abdominal aortic aneurysm and aortoiliac occlusive disease seem to be rather different manifestations of atherosclerosis than really dissimilar diseases. PMID- 4034045 TI - [Renal tolerance of an incremental dosage regimen of anturan in the aged with altered renal function]]. AB - The aim of the study was to investigate renal tolerability of a flexible increasing dose-schedule of anturan (E), dependent on basal serum creatinine values. 12 male cardiovascular elderly patients (mean age: 75 years; SD: 5.5 years) suffering from mild chronic renal failure (serum creatinine between 2.00 and 4.00 mg/100 ml) entered an open study of 2-month duration. Starting dosage was 200 mg per day; daily dosage was then increased every 4 days of 200 mg, or kept constant for another 4 days, according to each patient's renal function, up to 800 mg per day. All the patients reached the maintenance dosage of 800 mg/day in 12 days, because renal function didn't worsen. Two patients were withdrawn: one at the end of the 1st month of E therapy because of exitus due to myeloma, the other one at the 24th day of E therapy for serum creatinine increase, possibly related to ongoing therapy. Creatinine clearance significantly increased, serum creatinine and uric acid significantly decreased at the end of E therapy. The other biochemical examinations didn't change and no patient complained of any undesired effect during the whole study. The obtained results seem to prove that anturan, if an incremental dose-schedule is followed at the beginning of therapy is well tolerated even in elderly azotemic patients. PMID- 4034046 TI - [Various parameters of hemostasis in patients with chronic liver diseases]. AB - The aim of the study was to investigate the nature and the possible correlations between abnormalities of platelet function and haemostatic and fibrinolytic activity in a group of 33 patients with biopsy-proven chronic liver disease. A slight decrease in prothrombin activity, AT III and plasminogen levels was noticed in the patients studied. Significantly enhanced levels of intraplatelet 5HT was also found in patients with cirrhosis and in those with chronic active hepatitis. Changes in these parameters were generally independent from each other, the only correlation being found between prothrombin activity and AT III levels in patients with cirrhosis. PMID- 4034047 TI - [Control of nosocomial infections]. AB - Different factors involved in nosocomial infection and high risk hospital departments are examined. Methods of surveillance of infection in patients, in staff, and monitoring of environment and equipment are settled. The results obtained in environment monitoring and in some kinds of surgical operation are reported. A policy of epidemiological surveillance is proposed. PMID- 4034048 TI - [Infantile papular acrodermatitis. Description of a clinical case]. PMID- 4034049 TI - [Myelofibrosis caused by cancer: presentation of a clinical case with a very difficult diagnosis]. AB - Fibrosis of the bone marrow or myelofibrosis, is a connective tissue response of the bone marrow, giving rise to alterations of various nature. From an etiological point of view, it may be divided into primitive or secondary forms. Since the therapeutic implications differ, it is important to make a correct differential diagnosis between the 2 forms. With this in mind, particular importance must be given to myelofibrosis secondary to neoplastic metastasis since it frequently presents with a clinical and hematological picture and bone marrow morphology typical of acute or chronic idiopathic myelofibrosis. In such a situation the particular course of the disease and the description fibrosis sclerosis of the bone marrow are highly suggestive of myelofibrosis secondary to neoplastic metastasis. On the basis of these considerations, we found it interesting to report a case which came under our observations. The patient in this case presented a complex differential diagnosis which offered us the occasion to review and highlight the clinical and histological criteria fundamental to the 2 forms. The patient, a 40 year old woman, presented with a clinical picture typical of myelofibrosis following surgery for a cystic ovary. For 3 years she had felt violent bone pains and had progressively declined in her physical state to the point of cachexia. A careful histological exam of the bone marrow revealed metastasis from the gastric tumor thus giving a clear diagnosis of secondary myelofibrosis. PMID- 4034050 TI - [Prognosis of breast cancer (T1-4 No Mo) with reference to anatomo-pathological and clinical factors]. AB - Using methods of multivariate statistical analysis, the Authors analyse the prognosis of 135 patients affected by No Mo breast cancer treated with radical mastectomy alone. Among eight risk factors examined, "vascular invasion" and "peritumoral infiltration" seemed to have the greatest influence on prognosis. Therefore, more aggressive treatment may be considered for the patients affected by breast cancer with the two factors former quoted. PMID- 4034051 TI - [Risk factors in acute myocardial infarct and cerebral ischemic disease]. AB - Ten risk factors (RF) were sought and compared in 100 patients with acute myocardial infarct (MI) and 50 with cerebrovascular disease (CVD) on their first admission. No other diseases were present. Only 3 subjects were free of the RF. At least three RF were noted in 71 MI (71%) and 32 CVD (64%), and four or more in 51 (51%) and 22 (44%) respectively. The most commonly observed in both groups were: high total: HDL cholesterol ratio, cigarette smoking, hypertriglyceridaemia, arterial hypertension, hyperuricaemia Total blood cholesterol was more frequently above normal in MI (52%) than CVD (28%). The difference between the means was significant (p less than 0.01). No significant differences, on the other hand, were noted for the other RF. These findings suggest that the definition of RF for MI and CVD patients is both practicable and important in the secondary prevention of these two diseases. They also show that their atherosclerotic risk profile is substantially the same. PMID- 4034052 TI - [Ferritin, CEA and TPA as tumor markers in breast neoplasms]. AB - In order to assess the sensitivity and specificity of Ferritin, CEA and TPA as neoplastic markers in breast carcinomas, 91 patients all classified according to the TNM-UICC system were studied in a cancer clinic. The results of the analyses indicate that ferritin is apparently only influenced by the presence of metastatic neoplasias and that greater sensitivity is obtained if all three markers are employed simultaneously. PMID- 4034053 TI - [Verapamil inhibits the in vitro synthesis of DNA. I. Study of human lymphocyte cultures]. AB - Verapamil in vitro reduced 3H-TdR incorporation into lymphocytes. High doses of Verapamil were lethal for cells; low doses inhibit DNA synthesis, but cell viability by the Trypan blue exclusion method is preserved. Increasing the concentration of Ca++ in the medium partially improved lymphocyte viability and 3H-TdR incorporation. Modification of the Na+ and K+ content in the medium did not interfere with Verapamil action. The inhibitory action was not completely reversible even when the cells were exposed to the drug for a short time (15'). Our results confirm the dependency of lymphocyte blast transformation on Ca++ during the first 20 h. Nifedipine did not inhibit cell replication, which suggests a different mechanism of action. Our investigation suggests that there is more than one model for calcium-antagonism and that the action of Verapamil can not be explained only by its influence on transmembrane Ca++ flux. We believe that Verapamil has a negative action on cell metabolism directly through an interaction on transmembrane Ca++ flux and on intracellular Ca++. PMID- 4034054 TI - [Verapamil inhibits DNA synthesis in vitro. II. Study of the MCF7 and Jurkat neoplastic cell lines]. AB - Verapamil in cultures of mammary carcinoma MCF7 cells and Jurkat A.L.L. cells decreased the 3H-TdR incorporation. The action of Verapamil is dose-dependent. The inhibition percentage of 3H-TdR incorporation into Jurkat cells by Verapamil was lower than into MCF7 cells. No change of the mitotic inhibition was observed with higher Ca++ concentration in the medium. Modification of the Na++ and K++ content in the medium did not change action of Verapamil; this is in agreement with the independence of neoplastic cells from the culture medium. Our investigation suggests that Verapamil does not work through a block of transmembrane Ca++ flux, but rather through an intracellular interaction. PMID- 4034055 TI - [The behavior of various muscle enzymes in hypothyroidism]. AB - The behaviour in hypothyroidism of certain muscular enzymes (CK, TOE, LDH, AST) was studied. A significant increase in these enzymes occurs in basal conditions and is gradually normalised by substitution therapy. This response might serve to distinguish hypothyroidism from other conditions causing an increase in muscular enzyme levels. PMID- 4034056 TI - [First quantitative data obtained by HPLC of sugars present in hydrolysed placental acids]. PMID- 4034057 TI - [Quantitative determination of several types of collagen in the placenta as a function of its maturation]. PMID- 4034058 TI - [Quantification of fetal cardiac time intervals by mono-bidimensional echocardiography. Methodology]. PMID- 4034059 TI - [A case of renal angiomyolipoma in pregnancy]. PMID- 4034060 TI - [SLE and pregnancy. Presentation of a clinical case with diagnostic and therapeutic considerations]. PMID- 4034061 TI - [Efficacy of allylestrenol in the prevention of habitual abortion]. PMID- 4034062 TI - [Colpocytologic study in Siena and the province in the decade from 1973 to 1982]. PMID- 4034063 TI - [Total laparohysterectomy]. PMID- 4034064 TI - [Usefulness of a correct monitoring of prolonged pregnancies]. PMID- 4034065 TI - [Neonatal pathology and method of delivery in small-for-gestational-age neonates]. PMID- 4034066 TI - [Uterine leiomyomas with unusual histopathologic aspects. Presentation of 4 cases]. PMID- 4034067 TI - [Volvulus of the sigmoid in pregnancy]. PMID- 4034068 TI - [Presentation of a clinical case of rupture of the uterus in the 21st week of gestation, caused by interstitial pregnancy]. PMID- 4034069 TI - [Microsurgery and tubal sterility]. PMID- 4034070 TI - [Prenatal diagnosis of cardiovascular pathology using mono- and bidimensional echocardiography]. PMID- 4034071 TI - [Cervico-vaginal bacterial changes in women using an IUD]. PMID- 4034072 TI - [Elective appendectomy as a routine complementary intervention in cesarean section]. PMID- 4034074 TI - [Conservative therapy of breast carcinoma]. PMID- 4034073 TI - [Theoretical bases of preventive medical therapy]. PMID- 4034075 TI - [Therapy of carcinoma in situ]. PMID- 4034076 TI - [Follow-up in a patient treated for carcinoma of the breast]. PMID- 4034077 TI - [Hormonal receptors: methods and prognostic significance]. PMID- 4034078 TI - [Correlation between positivity of hormonal receptors and the finding of metastases in regional lymph nodes]. PMID- 4034079 TI - [Precautionary ovariectomy in the therapy of initial carcinoma of the breast. Our experience]. PMID- 4034080 TI - [Applicability to clinical practice of prospective studies of adjuvant medical therapy in surgically treated breast carcinoma. Clinical contribution]. PMID- 4034081 TI - [Bone marrow toxicity of chemotherapy combinations in operable carcinoma of the breast]. PMID- 4034082 TI - Changes in thalamic projection to the barrelfield of rat after neonatal lesions sparing one whisker. AB - The thalamic input to the barrelfield of rats with a solitary mystacial vibrissa (C3) intact was examined using succinic dehydrogenase techniques. Rats were lesioned on postnatal day (PD) 1 and brains examined at either 7, 12, 21 or 28 days later. The resultant segmentation in the hemisphere contralateral to the lesioned muzzle consisted of fused rows (A to E). At all ages row C differed from the other rows in that the center of the row was enlarged and separated from the row on either side of it. Thus the presence of a single vibrissa is sufficient to organize the thalamic input to its barrel. PMID- 4034083 TI - Transplantation of cultured fetal human adrenal chromaffin cells to rat brain. AB - Adrenal chromaffin cells, obtained from a therapeutically aborted human fetus of about 11 weeks gestation, were cultured for 3 weeks in vitro and then transplanted to the striatum of rats. Transplanted cells became established through strands of tissue growing into the host striatum. No signs of inflammation or rejection were observed up to the time of sacrifice one month post-transplantation. Histofluorescence examination of the implanted areas showed many clusters of cells having an intensely positive catecholamine fluorescence with some of the cells developing conspicuous processes. This study, showing survival of cultured human adrenal chromaffin cells transplanted into rat brain tissue, might indicate the feasibility of using cultured human material for future human neuronal transplantation studies as a therapeutic measure. PMID- 4034084 TI - Secondary transneuronal degeneration: cortical changes induced by peripheral nerve section in neonatal rats. AB - Secondary transneuronal degeneration of the cortico-spinal tract (CST) has been induced after sciatic nerve section in newborn rats. Observations made 21-60 days after the lesion showed a considerable decrease in number of myelinated and unmyelinated fibres of the CST ipsilateral to the lesion and of horseradish peroxidase-labelled nerve cells in the somato-sensorimotor cortex of the contralateral cerebral hemisphere. This phenomenon which has never been observed in spite of the frequent studies of experimental peripheral nerve lesions, may be significant in normal and pathological development. PMID- 4034085 TI - Electrical stimulation of the ventral noradrenergic tract (VNAT) releases hypothalamic noradrenaline and stimulates prolactin secretion in ovariectomized female rats treated with oestrogen. AB - Electrical stimulation of the ventral noradrenergic tract (VNAT) caused a significant fall in the hypothalamic content of noradrenaline in ovariectomized female rats which had been treated with oestrogen. No similar effect was observed in the cerebral cortex, which implies that the stimulation did not affect the dorsal noradrenergic tract. In parallel experiments with groups of similarly treated rats, VNAT stimulation was found to increase release of prolactin from the pituitary gland, and this increase was significantly enhanced in animals which had been stressed by fasting for 3 days. PMID- 4034086 TI - Cardiovascular responses and the sense of effort during attempts to contract paralysed muscles: role of the spinal cord. AB - To determine whether spinal transection affects the cardiovascular response and the sense of effort which accompany attempts to contract paralysed muscles in normal subjects, paraplegic patients tried to contract paralysed leg muscles. During attempted contractions, paraplegic subjects reported a sense of effort but did not change heart rate or blood pressure. However, these subjects had a normal cardiovascular response to handgrip contractions. These data suggest that pathways descending to and arising from the spinal cord below the lesion are required to generate a cardiovascular response but are not necessary for the sense of effort. PMID- 4034087 TI - Phylogenetic examination of vertebrate central nervous system myelin proteins by electro-immunoblotting. AB - Central nervous system (CNS) myelin proteins from vertebrate classes were examined by immunoblotting with antisera against mammalian CNS myelin proteins. Higher vertebrates possessed proteolipid (PLP), DM-20 and Wolfgram (WP) proteins, except that DM-20 was missing in amphibia. Fish CNS myelins contained neither PLP nor WP; instead they bound antisera to mammalian peripheral nervous system P0 protein. All classes carried myelin basic protein, but only mammals exhibited a component equivalent to rat 21.5K (21,500 dalton). These phylogenetic data are consistent with major changes in CNS myelin protein composition at the transition from fishes to higher vertebrates. PMID- 4034088 TI - Non-cholinergic globus pallidus cells that project to the cortex but not to the subthalamic nucleus in rat. AB - A substantial population of small globus pallidus neurons was demonstrated to have axonal projections to the cerebral cortex using fluorescent retrograde transport techniques. This population was separate from the more numerous population of medium size globus pallidus cells projecting to the subthalamic nucleus and was also separate from the pallidal and especially peripallidal population of large cholinergic cells projecting to the cortex. Some of the small, non-cholinergic cells projecting to the cortex also gave off axonal collaterals to the paraventricular thalamic nucleus. PMID- 4034089 TI - Inhibitory periphery effect in geniculate neurons after elimination of specific retinogeniculate excitation. AB - Stimulation of the outer periphery of a cell's receptive field with phase reversing gratings leads to mainly excitatory phasic or tonic responses in the dorsal lateral geniculate nucleus (dLGN) of the cat. This lateral excitation is of retinal origin. Following destruction of the retinal receptive field area by localized photocoagulation, pure inhibitory periphery effects are observed in the majority of deafferented cells. This inhibition acts beyond the boundaries of the antagonistic receptive field and is based on neuronal mechanisms on the geniculate level. PMID- 4034090 TI - The pattern of cortical projections from the intermediate parts of the magnocellular nucleus basalis in the rat demonstrated by tracing with Phaseolus vulgaris-leucoagglutinin. AB - The pattern and distribution of the cortical projections from intermediate parts of the cholinergic basal magnocellular nucleus were studied by anterogradely transported Phaseolus vulgaris-leucoagglutinin. This immunocytochemical tracing technique reveals the detailed morphology and distribution of efferents from this intermediate area in the nucleus basalis to the various areas and layers of cortex and amygdala. Major projections with a relatively high density of terminal boutons were found in layers I, II and VI of the frontal cortex, in layers V and VI of parietal and temporal areas, in the entire perirhinal and entorhinal cortices, and in the basolateral nucleus of the amygdaloid body. From the nucleus basalis area studied, few if any projections could be demonstrated to cingulate and occipital cortical regions. PMID- 4034091 TI - Visual deficits following intraocular treatment of chicks with glutamate or kainic acid. AB - After intraocular treatment with kainate or glutamate, chicks were tested for visual discrimination performance, pecking aim, bead detection, optokinetic response and pupillary response. Kainate at an amount of 6 nmol per eye impaired performance in all of the tests except pupillary response. No effects were seen after 0.6 nmol of kainic acid. Glutamate at 6000 nmol impaired performance on all tests but the optokinetic and pupillary response. Although glutamate caused less severe deficits in visual behaviour than the high dose of kainate, cellular organization of the retina, at least in some regions, was more disrupted in these animals. Glutamate at 600 nmol caused a late onset defect in visual discrimination performance but no effects on optokinetic response. PMID- 4034092 TI - On the binding of gamma-[3H]aminobutyric acid to the rat oviduct. PMID- 4034093 TI - A thalamic component of the cervical evoked potential in man. AB - Somatosensory evoked potentials (SEPs) were recorded simultaneously from scalp and neck locations following median nerve stimulation. By subtracting the latency of the major negative peak of the cervical SEP (N13) from that of the primary cortical response (N20), the central somatosensory conduction time was calculated (5.9 ms). On the descending slope of the cervical SEP was superimposed a positive potential of probable thalamic origin (P17). By subtracting the latency of N13 from that of P17 and P17 from that of N20 respectively, the transit time for the afferent volley both within the brainstem (3.9 ms) and the thalamo-cortical radiation (2.0 ms) was obtained. PMID- 4034094 TI - Demonstration of regional blood-brain barrier permeability in human brain. AB - The brain of a 78-year-old woman with argyria was examined at autopsy. Silver nitrate deposition was observed in circumventricular organs (CVO) and in the paraventricular and supraoptic nuclei of the hypothalamus. These findings parallel animal experiments of other investigators and are the best demonstration so far of regional absence of the blood-brain barrier in humans. These observations demonstrate similarities between humans and other mammals of CVO anatomy, permeability to blood-borne agents, and perhaps neural connections between CVOs and magnocellular nuclei. PMID- 4034095 TI - Neutral carrier sodium ion-selective microelectrode for extracellular studies. AB - A Na+-selective microelectrode based on a synthetic neutral carrier (ETH 157) is described. The selectivities in respect to K+, Ca2+ and Mg2+ are adequate for extracellular measurements of Na+ activities. Microelectrodes with tip diameters of about 0.7 micron have an electrical resistance of 3 X 10(10) omega and a 90% response time of less than or equal to 3 s. The drift of the potential difference of the Na+-microelectrode cell assembly in aqueous extracellular electrolyte solutions is less than or equal to 0.2 m V/3 h. PMID- 4034096 TI - Reciprocal connections between the caudal vermis and the vestibular nuclei in the rabbit. AB - The termination of secondary vestibulocerebellar mossy fibers and the localization of Purkinje cells giving rise to corticovestibular projections were visualized simultaneously in lobules IX and X after injections of wheat germ agglutinin-horseradish peroxidase in the vestibular nuclei of the rabbit. Vestibulocerebellar mossy fibers from the medial, descending and superior vestibular nuclei terminate in longitudinal strips in the granular layer, which coincide exactly with the localization of the labeled Purkinje cells. PMID- 4034097 TI - Direct projections of the hypothalamic nuclei to the thalamic mediodorsal nucleus in the cat. AB - Direct projections of the hypothalamic nuclei to the thalamic mediodorsal nucleus (MD) were studied using retrograde and anterograde transport of horseradish peroxidase (HRP) and wheat germ agglutinin (WGA)-HRP. HRP and WGA-HRP were injected into the MD, thalamic paraventricular, lateral habenular and hypothalamic nuclei. The results indicate that the MD, particularly its medial part, receives a moderate amount of hypothalamic afferents, and that most of these afferents originate in the medial part of the lateral hypothalamic nucleus at anterior levels, while a limited number are derived from the dorsal, dorsomedial, ventromedial and anterior hypothalamic and lateral preoptic nuclei. PMID- 4034098 TI - Immunohistochemical studies on mouse cerebral cortex grafted into the third ventricle of rats treated with cyclosporin A. AB - Newborn mouse cerebral cortex was transplanted into the third ventricle of an adult rat brain. After the operation, the immunosuppressant cyclosporin A was administered daily for two weeks, and the grafted tissue was examined immunohistochemically at the 4th week. Neurons, astroglias and oligodendroglias were positively stained by antibodies against neurofilament, glial fibrillary acid protein and 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNPase), respectively. The CNPase staining indicated that myelination had occurred in the grafted tissue. Thus both neuronal and glial elements in the grafted tissue could survive and mature in the third ventricle of the different species upon administration of cyclosporin A. PMID- 4034099 TI - Divergent action of verapamil perfused in two hypothalamic areas on body temperature of the cat. AB - Guide cannulae for push-pull perfusion were bilaterally implanted stereotaxically within the anterior hypothalamic, preoptic area (AH/POA) and posterior hypothalamus (PH) of the cat. Catecholamine-reactive sites were identified within AH/POA in which a microinjection of norepinephrine (NE) (5.0 micrograms) evoked a characteristic, transient hypothermia. Similarly the cation-reactive region within the PH was identified in which excess Ca2+ (25 mM) also evoked a hypothermic response. When verapamil was perfused at a rate of 25.0 microliters/min in a concentration of 0.4 or 2.0 micrograms/microliter within AH/POA at a NE-sensitive site, a concentration-dependent decline in the core temperature of the cat occurred. Conversely, verapamil perfused in the same manner with a Ca2+-reactive site caused an intense rise in the cat's body temperature which also was concentration dependent. These results show that the localized blockade of slow Ca2+ channels exerts direct, differential physiological effects within central nervous system tissue. In this case, verapamil mimics noradrenergic effects within the AH/POA; however, the hyperthermic response following Ca2+ channel blockade within tissue of the PH resembled that produced by ethyleneglycoltetraacetic acid or Na ions. PMID- 4034100 TI - Retinal ganglion cell survival is mediated by cell contact with immature rat astroglia. AB - The survival of identified retinal ganglion cells (RGGs) in vitro increased when they were plated over subcultured monolayers of astrocytes. Immunofluorescence labelling of these monolayers showed that over 85% of the cells were glial fibrillary acidic protein (GFAP) positive and consisted of large, flat immature astrocytes. Less than 7% of the total cell population in the monolayers were fibroblasts, leptomeningeal or endothelial cells. Coculturing of RGCs with subcultured astrocytes revealed that the trophic interaction between astrocytes and RGCs is mediated through cell contact. PMID- 4034101 TI - Organization of afferent connections to the lateral and interpositus cerebellar nuclei from the brainstem relay nuclei: a horseradish peroxidase study in the cat. AB - Afferent projections to the lateral (dentate) and interpositus cerebellar nuclei from the brainstem relay nuclei were studied in cats using the horseradish peroxidase (HRP) method. In the first series of experiments, HRP was injected into the brachium pontis. Mossy fiber terminals were anterogradely labeled, predominantly in the lateral (hemispherical) part, moderately in the intermediate part, and slightly in the vermal part of the cerebellum. Besides these terminals in the cerebellar cortex, axon terminals labeled anterogradely were also found in the cerebellar nuclei. The labeled terminals appeared almost exclusively in the lateral nucleus and rarely in the interpositus nucleus. Cells labeled retrogradely were found both in the pontine nuclei and the tegmental reticular nucleus, but not in other brainstem nuclei. In the second series of experiments, HRP was injected into the lateral and interpositus nuclei, and retrograde labeling was examined in the brainstem relay nuclei. After HRP injection into the lateral nucleus, the number of labeled cells was significantly large in the pontine nuclei, but fairly small in the reticular or vestibular nuclei. The number of labeled cells was generally large in the inferior olive, mainly in the principal olive. After HRP injection into the interpositus nucleus, the number of labeled cells was moderate in the reticular or vestibular nuclei, but small in the pontine nuclei. The number of labeled cells in the inferior olive was also large, being distributed mainly in the accessory olives. These results indicate that the pontine nuclei and the principal olive provide major afferent inputs to the lateral nucleus, whereas the reticular nuclei, the vestibular nuclei and the accessory olives are the major afferent sources to the interpositus nucleus. PMID- 4034102 TI - Cytoarchitectonic coincidence with the discontinuous connectional pattern in the deep layers of the superior colliculus in the rat. AB - The aims of the present study are to demonstrate cytoarchitectonically columnar structures in the deep layers of the rat's superior colliculus, and to show experimentally the existence of a clear correlation between the cytoarchitectonically defined columnar structures and the discontinuous patterns of the tectal connections in the deep layers. Injections of horseradish peroxidase conjugated to wheat germ agglutinin (HRP-WGA) into the prefrontal cortex produced orthograde labeling in the columnar structures in the deep layers of the superior colliculus, while HRP-WGA injections into the somatic sensory cortex resulted in orthograde labeling in the areas outside the columnar structures, so that the distribution patterns of terminals from these two different cortical areas are complementary in the deep layers. Cells of origin of the tectal efferents are also differentiated in terms of the columnar structures; HRP-WGA injections into the dorsal medial nucleus of the thalamus yielded retrograde labeling of spindle-cells within the columns, whereas the injections into the trigeminal sensory nuclei produced retrograde labeling of polygonal cells in the areas outside of the columns. These results suggest that as in the dorsoventral laminar coincidence with the tectal connections, there is a well organized mediolateral registration of the tectal connections with the cytoarchitectonically defined cell arrangement in the deep layers of the superior colliculus. PMID- 4034103 TI - [3H]Nicotine binding sites in developing fetal brains in rats. AB - [3H]Nicotine binding sites were examined in developing fetal brains in rats. The fetal brain membranes bound [3H]nicotine with a similar affinity to that of adult brain membranes. This binding was displaced by unlabelled nicotine or carbamylcholine, the inhibition concentrations being approximately the same for fetal and adult brain preparations. alpha-Bungarotoxin had no effect on [3H]nicotine binding to fetal brain membranes as well as to adult brain preparations. The specific [3H]nicotine binding was first detectable on day 16 of gestation and it increased several folds until birth. PMID- 4034104 TI - Responses of cerebellar Purkinje cells to mechanical perturbations during locomotion of decerebrate cats. AB - During the locomotion of cats which had been decerebrated at the precollicular and premammillary level, mechanical perturbations (taps of 50-550 g wt.) were applied to the paw dorsum of the left forelimb. Purkinje cells were recorded from the vermis of the cerebellar anterior lobe, and those connected to Deiters' neurons controlling the right forelimb were identified by antidromic and orthodromic stimuli. Taps on the left forelimb induced in these Purkinje cells two types of responses; I-type is a depression of simple spike discharge, often preceded by a brief phase of facilitation, and E-type is entirely a facilitation of simple spike discharge. Complex spikes, representing activation through climbing fiber afferents, were frequently evoked by the taps in both I- and E types. The I-type depression in Purkinje cells closely corresponds to the previously reported facilitation in Deiters' neurons and forelimb extensor muscles, suggesting that the interlimb coordination during cat's locomotion is effected by linked activity of vermal Purkinje cells and Deiters' neurons. PMID- 4034105 TI - Promotion of sprouting and synaptogenesis of cerebrofugal fibers by ganglioside application in the red nucleus. AB - The effect of gangliosides on sprouting of cerebrorubral synapses from the contralateral cerebral cortex was investigated following lesions of normal ipsilateral cerebrorubral synapses. It was found that, in cats in which ipsilateral cerebral ablations were performed at more than 2 months of age, the mean probability of occurrence of EPSPs induced in red nucleus neurons by stimulation of fibers from the contralateral cerebral cortex in the ganglioside treated group was significantly higher than in the untreated group. Therefore, ganglioside application appears to promote sprouting and formation of functional synapses in the red nucleus. PMID- 4034106 TI - Estrogen stimulates neuronal plasticity in the deafferented hypothalamic arcuate nucleus in aged female rats. AB - The hypothalamic arcuate nucleus (ARCN) was examined ultrastructurally 3 weeks after the complete deafferentation of the medial basal hypothalamus (MBH) with the island isolation technique in ovariectomized aged female rats (720-930 days of age). The mean numbers of axodendritic and axosomatic synapses in the ARCN decreased to about one-third of those in the intact controls. However, the treatment with estradiol benzoate (2 micrograms/day) during the 3 weeks following the day of brain surgery brought about a marked increase in the numbers of these synapses. The data suggest that the ARCN neurons of aged female rats still retain plasticity to react to deafferentation under influences of estrogen. PMID- 4034107 TI - Copper deficiency induced by megadoses of zinc. PMID- 4034108 TI - Neosugar--a fructooligosaccharide nonnutritive sweetener. PMID- 4034109 TI - Regulation of iron assimilation in microorganisms. PMID- 4034110 TI - Hypomagnesemia associated with other electrolyte imbalances. PMID- 4034111 TI - Glucose polymers enhance the intestinal absorption of calcium. PMID- 4034112 TI - Infant feeding practices in India. PMID- 4034113 TI - Iron overload associated with Hemoglobin Olympia. PMID- 4034114 TI - Regulation of mucosal enzymes by their dietary substrates. PMID- 4034115 TI - Aortal abnormalities in marginal copper deficit. PMID- 4034116 TI - A new pathway for conversion of glucose to glycogen is confirmed. PMID- 4034117 TI - Role of pyridoxal-5'-phosphate in vitamin K-dependent carboxylation. PMID- 4034118 TI - Maternal iron deficiency affects carnitine metabolism in rat pups. PMID- 4034119 TI - An overview of adult allergic disorders. AB - Stuffy nose, itchy and watery eyes, shortness of breath with wheezing, hives and stomach upsets often translate into allergic rhinitis, allergic asthma, urticaria and food allergies. These symptoms present a diagnostic dilemma to practitioners, even when sophisticated immunologic tests are available. Given a good history, however, the most common allergic disorders can be diagnosed and managed by nurse practitioners. In this article, an overview is presented which includes a discussion of four chronic adult allergic problems: rhinitis, asthma, urticaria and food allergies. A review of basic immunological principles is provided. Each condition is described in terms of data collection and assessment criteria. General client education guidelines follow. PMID- 4034121 TI - Malicious prosecution. PMID- 4034120 TI - Tetanus and the aged. AB - Tetanus is primarily a disease of the aged. Even though the overall number of cases of tetanus has decreased since 1955, the number of cases of tetanus in people 50 years of age and older has remained constant. The national Center for Disease Control attributes the cases of tetanus in the aged to inadequate immunization levels. Tetanus is preventable and, theoretically, could be eradicated if the population was at an adequate immunization level. There are many reasons why older people are not adequately immunized. These reasons may include the inability to get to a health care facility due to physical disability or lack of transportation, ignorance of the importance of seeking health care for minor injuries, financial constraints and a knowledge deficit on the part of health care providers regarding the immunization needs of the aged. Health care providers can prevent tetanus in the aged through vigilance. All aged clients should be routinely assessed and immunizations updated as necessary. Tetanus will never be eliminated until universal active immunization has been achieved. PMID- 4034122 TI - Oesophageal transit of liquid: effects of single or multiple swallows. AB - The effects of single and multiple swallowing on oesophageal transit have been evaluated in healthy subjects. It was shown that the transit patterns observed after multiple swallowing were different from that observed after a single swallow. It was concluded that for the detection of oesophageal transit abnormalities, the test should be performed using a single swallowed bolus. PMID- 4034123 TI - Overestimation of splenic size and underestimation of hepatic size by radiocolloid scintigraphy in advanced cirrhosis of the liver: an autopsy correlation. AB - The radiocolloid liver-spleen scintigrams of seven patients with advanced cirrhosis of the liver were correlated with autopsy results. The data showed scintigraphic overestimation of splenic size and underestimation of hepatic size. The causes of underestimation of the liver size were: rotation of the liver due to ascites; photon attenuation by ascitic fluid; and/or decreased and in homogeneous distribution of radiocolloid in the diseased liver. The splenic size/weight was overestimated because of lack of the effects of ascites and the usually marked increase in splenic radioactivity. Awareness of the underestimation of the liver weight/size and overestimation of the splenic weight/size occurring on the radiocolloid liver-spleen scan of patient with advanced alcoholic cirrhosis of the liver may help avoid misinterpretation. PMID- 4034124 TI - Hyperacute complete common bile duct obstruction demonstrated with 99Tcm-IDA cholescintigraphy. PMID- 4034125 TI - Right ventricular ejection fraction determined in three projections. AB - The right ventricular ejection fraction (RVEF) was successively determined in three projections in ten healthy volunteers aged 28-53, mean 37 years, with a first-pass technique using 99Tcm-labelled red blood cells and a gamma camera coupled to a computer. In the anterior-posterior projection (AP) the mean RVEF was 39.3%, range 26-49%, in the left anterior oblique (LAO) 43.7% (36-58), and in the right anterior oblique (RAO) 44.5% (36-54). These mean values do not differ significantly (P = 10%). The results from one of the subjects were withdrawn, as they deviated markedly from the general pattern, and the data were reanalysed from the remaining 9 subjects. Now the mean RVEF in the AP projection was 38.2%, which is significantly lower (P = 1%) than the corresponding RVEF of 44.3% in the LAO projection and of 45.2% in the RAO projection. Our results suggest that when using the classic first-pass technique, the right ventricle histograms will in any projection be influenced by the activity in the right atrium and the large vessels. PMID- 4034126 TI - The synthesis and evaluation of radioiodinated 14-(iodophenyl)-3 (R,S)methyltetradecanoic acid. AB - Radiohalogenated fatty acids (FA) labelled with gamma-emitting isotopes have a potentially important application in studies of impaired myocardial perfusion and metabolism. Evaluation of straight-chain fatty acids radiolabelled in different positions on the FA chain has been reported by many groups. In this paper we extended our recent studies using the betamethyl branched-chain fatty acid. The synthesis, labelling and preliminary evaluation of 131I- and 123I-14-(iodophenyl) 3-(R,S)methyltetradecanoic acid (I-PBMTA) are reported. This radiolabel concentrates in the mouse myocardium with 16% injected dose g-1 and 11% injected dose g-1 at 15 and 30 min, respectively. The images of the canine heart postinjection indicate a high myocardial extraction of the label with activity retained over an hour. The rate of washout of the activity from the heart was very low. This analogue is a potential agent for myocardial imaging studies. PMID- 4034127 TI - Combination of tissue polypeptide antigen (TPA) and carcino embryonic antigen (CEA) in different types of cancer. AB - Tissue polypeptide antigen (TPA) and carcino embryonic antigen (CEA) were measured in 55 patients with cancer in different locations (21 lung cancer, 133 breast cancer, 9 stomach cancer, 5 colorectal cancer, 7 cancer of unknown origin). TPA gives elevated values in all types of cancer. The statistical analysis shows that TPA is about equally sensitive for all cancer types, while CEA has a particularly high sensitivity for colorectal carcinoma. The TPA values in the group of cancer patients is significantly different from those in a group of healthy controls. TPA gives higher sensitivity than CEA in all tumour locations. By the use of combined determination of TPA and CEA the sensitivity can be further increased, to 64% for the whole patient population and 89% for the gastric tumour patients, even when the cut-off values are chosen so high that no false positives are obtained in either reference group (150 Ul-1 for TPA, 10 ng ml-1 for CEA). A limited correlation exists between the markers in tumour patients. PMID- 4034128 TI - Region of interest, ROI, analysis--confidence in derived parameters? PMID- 4034130 TI - Health and safety needs detailed in new asbestos abatement survey. PMID- 4034129 TI - Disseminated intravascular coagulation--the clinician's dilemma. AB - Disseminated intravascular coagulation is a complex syndrome involving inappropriate activation of the coagulation and subsequently fibrinolytic systems. It may occur in conjunction with a variety of disease states. The diagnosis must be based on a series of laboratory tests which provide indirect evidence of the process. Treatment consists of general supportive measures and elimination of the activating source of the coagulopathy. Additional therapy is dictated by individual circumstances. PMID- 4034131 TI - Chemical protective clothing: certification of performance. PMID- 4034132 TI - Universities can interest students in benefits of occupational medicine. PMID- 4034133 TI - Eye safety and health programs can improve productivity and profits. PMID- 4034134 TI - Accident/illness statistics are not effective if they are confusing. PMID- 4034135 TI - ABCs of safe driving. PMID- 4034136 TI - Clearing up the public's misconceptions about health care. PMID- 4034137 TI - The dangerous patient: how to assess them, how to manage them. PMID- 4034139 TI - Recognizing and treating the victims of violence. PMID- 4034138 TI - The doctor as victim: it can happen to you. PMID- 4034140 TI - Physicians liability in child abuse reporting cases. PMID- 4034141 TI - Cries of the children: are physicians listening? PMID- 4034142 TI - The current role of suction assisted lipolysis. PMID- 4034143 TI - High-dose 1-beta-D-arabinofuranosylcytosine in advanced breast cancer. AB - Twenty-two patients with metastatic breast cancer refractory to conventional chemotherapeutic agents were treated with 1-beta-D-arabinofuranosylcytosine (Ara C) at a dose of 2 g/m2 over 2 h every 12 h for 3 doses at 21-day intervals. Two patients achieved partial remission, 3 patients had less than partial response. PMID- 4034144 TI - Determination of tissue polypeptide antigen (TPA) levels in different cancer types and controls. AB - The clinical significance of the radioimmunological determination of tissue polypeptide antigen (TPA) was studied in 1980 and 1981 in patients with different cancer types (cancer of the gastrointestinal tract, cancer of the genitourinary tract, cancer of the lung and other malignancies) as well as in patients with acute inflammatory diseases, other benign diseases and healthy controls. TPA levels were elevated in about 70% of patients with acute inflammatory diseases and in 50-80% of patients with malignancies having evidence of disease (ED). In all other groups, as healthy controls, benign diseases except inflammatory diseases and cancer patients who had no evidence of disease (NED) or partial remission (PR), TPA was above the normal range in 4-17%. Comparisons between cancer patients with ED and cancer patients with NED/PR, healthy controls and patients with benign diseases (without acute inflammatory diseases) have shown a significant difference (p less than 0.01). Data from a follow-up program from the years 1982 to 1984, including TPA determinations, are shown. TPA can be regarded as an additional 'marker' for proliferative processes. The test seems to be useful for monitoring cancer growth in advanced cancer patients who received chemo- or radiotherapy. Limitations result from the lack of tumor specificity of the marker TPA. PMID- 4034145 TI - 12-O-Tetradecanoylphorbol-13-acetate promotion of carcinogen-treated rat liver endothelial cells. AB - Established RLC-1 adult rat liver endothelial cells were utilized to assess promotional requirements of hepatic endothelial elements to malignant transformation following in vitro exposure to carcinogens requiring metabolic activation. Diethylnitrosamine failed to transform RLC-1 cells with or without tetradecanoylphorbol acetate (TPA) promotion. Benzo (a) pyrene was previously shown to initiate certain growth changes in the RLC-1 line; these cells, however, required TPA promotion prior to expression of the fully transformed phenotype. PMID- 4034146 TI - Pathological analysis of the carcinogenicity of sodium o-phenylphenate and o phenylphenol. AB - Potential carcinogenicity and promoting effects of sodium o-phenylphenate (OPP Na) in two-stage urinary bladder carcinogenesis were shown in male F344 rats pretreated with 0.01% N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN). However, o phenylphenol (OPP) did not enhance the occurrence of urinary bladder lesions in rats pretreated with BBN. Scanning electron microscopy of OPP-Na-treated animals demonstrated a dose-dependent production of pleomorphic microvilli on the luminal surface of bladder superficial cells, whereas these were not observed with OPP. These results give some support to the conclusion that OPP-Na may be carcinogenic in the urinary bladder of male rats. PMID- 4034148 TI - Electrical resistivity of a tumor. AB - The resistivities of a Swarm murine basement membrane sarcoma and also surrounding tissue in BALB/c mice were determined. The circuit used allowed resistivity to be measured independently of the electrode geometry and capacitance. The tumor exhibited a resistivity of 310 +/- 52 omega X cm and the tissue 653 +/- 142 omega X cm. PMID- 4034147 TI - Cell surface alterations in murine leukaemia P388 adriamycin-resistant cells: studies on lectin-induced agglutination and rearrangement of lectin receptors. AB - Cell surface alteration was studied in a subline of murine lymphocytic leukaemia resistant to the broad-spectrum anticancer agent adriamycin (P388/ADR) employing concanavalin A(Con A)-induced agglutination and rearrangement of lectin receptors. Con A induced more agglutination of P388/ADR when compared to the drug sensitive parental cell line (P388/S). Studies on the redistribution of Con A and Ricinus communis agglutinin-I revealed a high percentage of P388/ADR showing internalized fluorescence, while a majority of P388/S displayed a uniform distribution of fluorescence on the cell surface. PMID- 4034149 TI - Scanning electron microscopy of the lingual dorsal surface of the beagle dog. PMID- 4034150 TI - Scanning electron microscopy of the lingual dorsal surface of the Japanese lizard, Takydromus tachydromoides. PMID- 4034151 TI - The branching site of the posterior adrenal artery in pigs. PMID- 4034152 TI - The anterior meningeal artery and other meningeal branches of the rabbit. PMID- 4034153 TI - A case study of radial artery absence. PMID- 4034154 TI - Abstracts of the 25th meeting of the Association for Eye Research. Lund, Sweden, August 28-31, 1984. PMID- 4034155 TI - Intercellular junctions in the developing rat corneal endothelium. AB - The surface events which occur during the morphogenesis of the corneal endothelium were studied in the rat with special attention to intercellular contacts, using scanning and transmission electron microscopy, and freeze fracture technique. Confluency was reached at the 16th-17th day of fetal development. As soon as adjacent cells make contact, marginal interdigitated finger-like processes developed and apical cell junctions appeared, namely tight and gap junctions. Tight junction networks progressively developed, girdling the apical side of lateral membranes, nevertheless, they remained very irregular in their apicobasal thicknesses. At every stage studied, neutralized lanthanum used as an ultrastructural tracer was seen filling the intercellular clefts and junction domains. Hence, the apical junctions do not constitute an impermeable barrier to this tracer in the developing corneal endothelium. PMID- 4034156 TI - Fine structure of the retinal pigment epithelial region of the archerfish (Toxotes jaculatrix). AB - The structure of the retinal pigment epithelium, choriocapillaris and Bruch's membrane has been studied by electron microscopy in the archerfish Toxotes jaculatrix. The pigment epithelium is composed of a single layer of large columnar cells. Each epithelial cell displays numerous small mitochondria, smooth endoplasmic reticulum, myeloid bodies, phagosomes and melanosomes. Rough endoplasmic reticulum and ribosomes while present are not abundant. The scleral or basal border of the epithelial cells is but minimally infolded whereas the vitreal or apical surface displays many elongated processes which surround the inner and outer segments of the photoreceptors. Laterally the epithelial cells are joined by a series of basally located cell junctions. Unattached phagocytic cells are a constant feature both between the retinal epithelial cells and within Bruch's membrane. The endothelium of the choriocapillaris bordering Bruch's membrane is typically very thin with a few fenestrations. Bruch's membrane lacks a central elastic layer and is composed of only three layers. Although only light adapted specimens were examined, it is felt that the melanosomes are capable of retinomotor movements. PMID- 4034157 TI - Effects of ocular blood flow changes on the efferent activity of cat ciliary nerves. AB - The efferent activity of the short ciliary nerves was studied in 23 anesthetized cats. Spontaneous activity was recorded in all preparations, and 33% showed a rhythmic discharge. Ipsilateral common carotid occlusion (ICCO) at constant intraocular and arterial pressures changed the discharge frequency in 14 of 33 filaments. Of these, 13 filaments showed a decrease in their firing frequency whereas in only one the discharge increased. Contralateral common carotid occlusion (CCCO), at constant intraocular pressure, changed the firing frequency in 8 of 20 filaments: 5 of them showed a decrease in their discharge frequency, whereas in 3 of them the discharge increased. This occurred when systemic arterial pressure was allowed to increase. These results suggest the presence of an efferent pathway involved in the nervous modulation or control of intraocular blood flow, aqueous humor dynamics, and/or intraocular pressure. PMID- 4034158 TI - Vasoactive intestinal polypeptide (VIP)-immunoreactive nerve fibers in the anterior uvea of the guinea pig. AB - The presence of vasoactive intestinal polypeptide (VIP)-like immunoreactivity, especially in the anterior part of the guinea pig uvea, was studied using an indirect immunofluorescence technique. In the ciliary body, thin varicose VIP fibers displaying VIP immunoreactivity were observed in the ciliary muscle and in the ciliary processes. The iris was virtually free of VIP fibers. In the choroid, VIP-immunoreactive fibers were seen mainly in close association with the choroidal blood vessels. The histochemical localization of VIP-immunoreactive fibers in the anterior uvea suggests that the physiological role of neuronal VIP in the uvea is not only associated with the regulation of the blood flow of the choroid but also with the functions of ciliary muscle and ciliary epithelium. PMID- 4034159 TI - Binocular disparity in visual evoked responses. Clinical evidence in normal and stereoblind subjects. AB - The authors have utilized a binocular flat or stereoscopic pattern (grating) to record visual evoked responses (VER) in normal and strabismic subjects. The aim was to find an electrophysiological correlate with the degree of binocular interaction in these subjects. The perception of the grating as tridimensional or flat derived from the disparity obtained with Polaroid filters placed in front of the eyes. In normal subjects, the results demonstrated a significant increase of VER amplitude during tridimensional perception of the pattern. In strabismic subjects the electrophysiological response was not correlated with the binocular conditions. PMID- 4034160 TI - Low temperature and acrylamide inhibit lens opacification caused by calcium. AB - We studied lens opacification of rabbit lenses in culture. Opacification was produced by maintaining rabbit lenses in medium containing calcium concentrations as high as 10 mmol/l and the opacity was measured using LASER spectroscopy. Increasing calcium caused significant opacification in lens cortex while the transparency in lens nucleus was unchanged by these concentrations. The cortical opacity was inhibited by low temperature and acrylamide. The maximum inhibition of opacity occurred at a concentration of 1% acrylamide and a temperature of 4 degrees C. The opacification due to a phase separation in nuclear cells was unaffected by these concentrations of calcium. PMID- 4034161 TI - Malignant teratoid medulloepithelioma in an adult. AB - A 50-year-old man presented with a reddish, well-vascularized mass in the region of a nasal iridodialysis of his left eye, pushing the whole iris in this sector forwards; the mass had a pinkish, partly cystic appearance in the pupil. The tumour was transparent on diaphanoscopy. A-scan sonography revealed a solid tumour of the ciliary body with partial retinal detachment suggesting a malignant melanoma. Fluorescein biomicroscopy did not confirm this suspicion. The enucleated eye demonstrated a malignant teratoid medulloepithelioma of the whole nasal and lower ciliary body, infiltrating the deep iris stroma, the anterior choroid, the neighbouring vitreous body and spreading along the inner retinal surface back to the equator of the eye. The occurrence of medulloepithelioma in adult and senior persons is rather exceptional and this is the reason for this publication. PMID- 4034162 TI - Some ultrastructural aspects of the vitreoretinal juncture. AB - The ultrastructural study of the vitreoretinal juncture was carried out by comparing two groups of patients: 6 young subjects under 25 years and 6 older subjects over 70. Retinal samples were taken from the posterior pole, the equator and the extreme periphery. Our work shows that the morphological modifications of the vitreoretinal juncture during the aging process vary following location. The most original alteration, never observed before, appears in the equatorial region: it consists of a widening of the intercell space filled with fibrils adhering to Muller's cells. It builds up an adhesion zone between the vitreous and the retina which is not visible during clinical investigations; it can create a tear during the posterior vitreous detachment. PMID- 4034163 TI - Pupil increment thresholds are influenced by color opponent mechanisms. AB - Pupillomotor and sensory spectral sensitivity curves of light-adapted eyes were compared. Experimental conditions were designed to favor (despite the threshold criterion) opponent processing of signals: long (500-ms) stimuli of large diameter (60 degrees) were presented centrally on an intense (16 cd/m2) white background. Narrow spacing of monochromatic stimuli permitted the recording of peaks and troughs in the increment spectral sensitivity curve which neither coincided with the characteristics of receptor pigment absorption spectra nor with the V-lambda curve. They are considered as showing influences of opponency mechanisms. Pupillomotor spectral sensitivity paralleled the sensory one, exhibiting the influence of opponency mechanisms on the pupil. Using more physiological conditions, human photopic spectral sensitivity was revealed as a three-peaked function, in sensory as well as in pupillomotor terms. PMID- 4034164 TI - Oscillatory potentials of the electroretinogram in patients with unilateral optic atrophy. AB - The oscillatory potentials (OP) of the electroretinogram (ERG) of 26 patients with unilateral optic atrophy were studied. The severity of optic atrophy was graded according to clinical findings. Three groups of increasing interocular difference in contrast sensitivity and changes of the visual evoked cortical potentials were obtained. No significant difference between the amplitudes or peak latencies of the individual oscillatory peaks or summed amplitudes of the OPs between the affected and control fellows eyes in any group was found. Neither was there any significant interocular differences regarding the a- and b-waves. These findings show that there does not seem to be any major contribution of ganglion cell activity in the generation of the OPs. Secondly, the results do not support the existence of centrifugal optic nerve innervation of the human retina. PMID- 4034165 TI - Epidemiology of acute angle-closure glaucoma: incidence and seasonal variations. AB - 126 cases of acute angle-closure glaucoma were encountered in the total population of the Israel Negev region during 12 years. This constitutes an incidence of 4.2/100,000/year in the total population and 11.1/100,000 in the over-30 population. The female:male ratio was 2.1:1 and the most frequently affected age-group was the 51-60 one; when age adjustment was made for the total population, the risk was equally high for all ages above 50. The ethnic origin had no effect on the incidence. A statistically significant preponderance of attacks occurring during summer and winter was found. PMID- 4034166 TI - [Changes in retinal hemodynamics in old age]. AB - The influence of increasing age on the haemodynamics of the retina was examined in a prospective study using 377 consecutive videoangiograms. A significant alteration of the arm-to-retina time and the arterial, capillary and venous phases of the retinal circulation is not detectable before the 60th year of life. After the age of 60 all circulation times change in a negative sense. A further, pronounced slowing of retinal circulation appears after the 75th year of life. This shows that the well-known morphological alterations in the retinal vessels in old age are accompanied by haemodynamic changes. PMID- 4034167 TI - [Unusual ocular anomaly in 9 p trisomy: retinal depigmentation]. AB - A new case of 9 p trisomy is reported in a 7-month-girl having typical morphological abnormalities and a mental retardation. During the examination, unusual ocular abnormalities were observed: pigmented linear dots of the mid peripheral retinal. Strabismus and hypertelorism were present. However, the other ocular features, blepharophimosis, correctopia, ptosis, microphthalmia, iris coloboma, unusual position of the eyelashes were not observed. PMID- 4034168 TI - Delayed corneal wound healing following radial keratotomy. AB - Four human corneal specimens obtained 5 to 47 months following radial keratotomy were evaluated by correlative microscopy. Repeat radial keratotomies had been performed in two cases. We documented gaping keratotomy incisions, epithelial plugs, and epithelial-lined incisions. In all cases, Bowman's layer was malapposed with slight to moderate fibroblastic activity at the incision sites. Epithelial and endothelial radial ridges were seen in two cases. No endothelial damage was seen under the radial incisions. The morphological evaluation of these specimens show the potential for a poor wound-healing response when corneas with previous corneal surgery and/or pathologic states undergo radial keratotomy. PMID- 4034169 TI - Excimer laser ablation of the cornea and lens. Experimental studies. AB - The pulsed ultraviolet excimer laser has been used to produce tissue ablation with a high degree of precision and with minimal thermal damage to adjacent structures. In comparative studies of excimer laser ablation of the cornea and crystalline lens using 193 nm and 248 nm radiation, threshold fluence for corneal and lens ablation was higher at 248 nm than at 193 nm. Ablation of corneal stroma at 193 nm produced the most precise cuts. When examined by transmission electron microscopy, a narrow zone of damaged tissue (0.1 to 0.3 micron) was seen immediately adjacent to the tissue removed by the laser. Ablation with 248 nm radiation produced incisions with ragged edges and with a wider and more severe zone of damage in adjacent stroma. Ultraviolet spectral transmission studies of the corneal stroma showed that absorption is 10 times greater at 193 nm than at 248 nm. The excimer laser was effective in producing well controlled ablation of the crystalline lens in vitro, with effects parallel to those seen in the cornea. PMID- 4034170 TI - An ultrastructural study of corneal incisions induced by an excimer laser at 193 nm. AB - Far ultraviolet light (193 nm) produced by an excimer laser has been used to produce a variety of incisions in the corneas of anaesthetised rabbits. Tissue was lost from the site of irradiation but the nature of the underlying molecular interactions responsible for such tissue erosion remain obscure. Ultrastructural analysis of the walls of the ablated areas show damage to the adjacent structures to be confined to a zone 60 to 200 nm in width. These dimensions could either be attributed to photochemical processes in which high energy photons directly break organic molecular bond, or to thermal reactions which result in limited heat flow and damage confined to the absorption depth at 193 nm of less than 1 micron. In non-penetrating incisions that reached within 40 micron of Descemet's membrane, endothelial cells were lost beneath the line of the irradiation. This spalling of cells seemed to be generated by shock or acoustic waves. PMID- 4034171 TI - Retinal acuity evaluation with the potential acuity meter in glaucoma patients. AB - The potential acuity meter (PAM) is designed to evaluate retinal acuity in the presence of media opacities. We looked at patients with glaucoma but with clear media, and compared best corrected visual acuity with PAM results to see if they produced comparable results. Sixty eyes in 38 glaucoma patients and 20 eyes in 10 normal ocular patients were evaluated. Our results indicate that PAM visual acuity is a reliable indicator of Snellen visual acuity in normal eyes, in eyes with mild to moderate glaucomatous damage, and when PAM visual acuity measurements were better than 20/60. However, when visual field loss is severe and when PAM visual acuity readings were worse than 20/60, the correspondence between these and Snellen visual acuity was erratic. Poor PAM results will not correlate with postoperative visual acuity in patients with advanced glaucoma and cataracts. PMID- 4034172 TI - Color contrast perimetry. The spatial distribution of color defects in optic nerve and retinal diseases. AB - Color contrast perimetry was used to evaluate central visual field defects in a group of 28 patients with visual loss resulting from optic nerve or retinal diseases. Kinetic perimetry was performed using colored test objects of constant luminance, equated to a white surround of 10 ft lamberts. Colored test objects were varied in size and in extent of color saturation. Test object color saturation was varied from a white that matched the color and luminance of the adapting background toward either the blue or the red color maxima of a video tangent screen. All central visual field defects that were demonstrable by luminance contrast perimetry were also detected by color contrast testing, and no defects were found for color contrast detection that could not also be demonstrated by conventional luminance increment perimetry. Retinal diseases usually produced scotomas for both color and luminance contrast detection, while optic nerve disorders tended to produce global depressions of both color and luminance contrast sensitivity across the entire visual field in addition to scotomas. There was no systematic difference in visual field defects for either class of disease when comparing color contrast in the blue (tritan) versus the red (protan) axes of color space. The apparent tritan or protan/deutan axes of color confusion found by hue discrimination testing in acquired dyschromatopsias may be determined by the relative spatial distribution of defects in the central visual field rather than by selective impairment of neural mechanisms for color or luminance information processing. PMID- 4034173 TI - Superior division paresis of the oculomotor nerve. AB - Five patients with isolated ptosis and a paresis of ocular elevation in abduction consistent with an isolated superior division III nerve palsy are reported. In all instances the III nerve appeared to be involved before its reported anatomic bifurcation into a superior and an inferior division, in the anterior cavernous sinus. PMID- 4034174 TI - Drusen of the optic nerve head. An important model. AB - It is proposed that drusen of the optic nerve head (ONH) may provide a useful model for the study of diseases which affect the vicinity of the optic disc. Several sensitive and revealing tests of inner retinal/optic nerve function have been applied in this investigation. Fundus Photo Perimetry has confirmed that little correlation exists between visual field defects and the location of ophthalmoscopically visible ONH drusen. The Flashing Repeat Static Test (FRST) was found to be abnormal in half of our patients, indicating probable ascending dysfunction in optic nerve fibers beyond the lamina cribrosa. Alterations in transient-like and/or sustained-like functions, found in several cases, are thought to represent effects of dysfunction descending to the retinal plexiform layers. PMID- 4034175 TI - Mapping X-linked ophthalmic diseases. Provisional assignment of the locus for choroideremia to Xq13-q24. AB - Choroideremia (McK 30310), an X-linked hereditary retinal dystrophy, causes nyctalopia, progressive visual field loss, and ultimately central blindness in affected males in early adulthood. We have used restriction fragment length polymorphisms from the X-chromosome to localize the region of the mutation for choroideremia in three families with this disorder. One polymorphic marker, DXYS1, located within Xq13-q21, shows no recombination with choroideremia at a LOD score of 5.78. Thus choroideremia maps within 9 centiMorgans of DXYS1 at 90% probability. Another marker, DXS11, located at Xq24-q26, shows no recombination with choroideremia but at a smaller LOD score of 1.54. These results suggest that the locus for choroideremia is distal to DXYS1 and between the two markers in the region Xq13-q24. This information may be useful for antenatal diagnosis, isolation of the mutant gene, and development of a rational therapy for the disorder. PMID- 4034176 TI - Cataract surgery following cobalt-60 plaque radiotherapy for posterior uveal malignant melanoma. AB - We reviewed the records of thirteen patients with posterior uveal malignant melanoma who had developed a mature radiation cataract following cobalt-60 plaque radiotherapy. Cataract extraction had been performed in seven of these patients as of the survey date of this investigation. We attempted to determine if cataract extraction increased the risk of metastatic melanoma, improved or worsened visual function, or resulted in any consistent intraoperative or postoperative complications that did not occur if the cataract was retained. Our analysis showed that removing the cataract did not appear to increase the risk of death from metastatic melanoma, but it also indicated that cataract extraction did not seem to improve the visual function of the irradiated eye. On the basis of our experience to date, we offer suggested guidelines for the management of patients who develop a mature cataract following cobalt-60 plaque radiotherapy of a posterior uveal malignant melanoma. PMID- 4034177 TI - Cataract surgery and intraocular lenses in patients with unsuspected malignant melanoma of the ciliary body and choroid. AB - During a recent four-year period, 21 patients were referred to the Oncology Service at Wills Eye Hospital with previously unsuspected posterior uveal melanomas in an eye that had been operated upon for a unilateral cataract. Twelve of the 21 patients had undergone standard cataract extraction and nine had had implantation of an intraocular lens, which was often in juxtaposition to the unsuspected melanoma. Preoperative ultrasonography in these patients had apparently been performed only to obtain an axial length of the globe and the eye was not scanned for pathologic processes in the posterior segment. Management of the melanoma included a cobalt plaque in eleven cases, enucleation in five, periodic observation in three, iridocyclochorioretinectomy in one, and orbital exenteration in one. It is stressed that a thorough external and slit-lamp examination, transillumination, carefully performed ultrasonography and, if necessary, a radioactive phosphorus uptake test can establish the diagnosis of uveal melanoma and prevent diagnostic delay and misdirected therapy in such cases. PMID- 4034178 TI - Projection-simulated ametropia. A model for teaching subjective refraction. AB - Teaching subjective refraction techniques ("refractometry") is enhanced by having the student experience the effect of each lens change "through the eyes of the patient." A projector, positioned behind the phoropter, projects a visual acuity chart through the phoropter onto the far wall. "Unknown" refractive errors are simulated by attaching trial lenses to the lens barrel of the projector, and the student progressively clears the projected image as he learns the standard steps of subjective refractometry. The focus sensitivity of each lens change can be varied, if desired, by stopping down the projection system. This simulation, which uses equipment readily available in most ophthalmology offices, has proven useful for both demonstration and practice. PMID- 4034179 TI - A case of pulmonary tuberculosis presenting with a choroidal tuberculoma. AB - A 17-year-old woman was referred because of a choroidal mass, with marked decrease in vision, in her left eye. Her medical history was negative. However, preliminary examination revealed a positive skin tuberculin test (PPD) and a chest x-ray picture of pulmonary tuberculosis. Bronchoscopy documented the diagnosis. Findings of other systemic investigations were negative. Fluorescein angiographic findings were compatible with the clinical diagnosis of a choroidal tuberculoma. A regimen of antituberculous medications was started, and both the choroidal and the pulmonary lesions gradually subsided. To our knowledge this is the first reported case of nonmiliary tuberculosis that presented solely with a choroidal lesion. PMID- 4034181 TI - [Incidence of diarrhea caused by toxin-producing Clostridium difficile in Hungary]. PMID- 4034180 TI - [Possibilities of exercise radioisotope ventriculography in the detection of ischemic heart disease]. PMID- 4034182 TI - [Endoscopic retrograde cholangiopancreatography in childhood]. PMID- 4034183 TI - [Characteristics of certain types of limb reduction abnormalities]. PMID- 4034184 TI - [Lymphoid follicular hyperplasia of the small intestine]. PMID- 4034185 TI - [Differential diagnostic difficulties in sporadic Q fever]. PMID- 4034186 TI - [Cortical erosion of the bare area of the femoral neck in irritable hip joints of alcoholics]. PMID- 4034187 TI - [Traumatic rupture of the uterus associated with pelvic fracture]. PMID- 4034188 TI - [Immunotoxicology. Its field of research, clinical significance, practical results]. PMID- 4034189 TI - [Follow-up examination of the growth of high birth-weight infants at one year of age]. PMID- 4034190 TI - [Experience with the implantation of a LeVeen shunt]. PMID- 4034191 TI - [Low serum HDL cholesterol levels in progeria]. PMID- 4034192 TI - [Pseudoresistance to DDAVP in diabetes insipidus]. PMID- 4034193 TI - [Viral hepatitis vaccination and related problems]. PMID- 4034194 TI - [Attempt at estimating the incidence of juvenile non-insulin-dependent diabetes mellitus]. PMID- 4034195 TI - [Incidence of Mycoplasma hominis in men examined for infertility]. PMID- 4034196 TI - [The so-called one-and-a-half syndrome. Significance of horizontal ocular movement disorders in the diagnosis of pontine processes]. PMID- 4034197 TI - [In what respect is Duhring's dermatitis a skin disease?]. PMID- 4034198 TI - [Significance of brain scintigraphy in the diagnosis of chronic subdural hematoma]. PMID- 4034199 TI - [Intraabdominal hemorrhage as an unusual complication of liver cirrhosis]. PMID- 4034200 TI - [Roentgen-morphometry and photon absorptiometry studies in normal subjects and patients with metabolic bone diseases]. PMID- 4034201 TI - [Changes in the exocrine function of the pancreas following surgical management of biliary diseases]. PMID- 4034202 TI - [Pulmonary manifestations of extrathoracic sarcoidosis without pulmonary roentgenologic signs]. PMID- 4034203 TI - In liability insurance, complexities abound. Interview by Mary Uehlein. PMID- 4034205 TI - Public principles, private lives. PMID- 4034204 TI - Erosion of confidence. PMID- 4034206 TI - Should you invest in convertible securities? PMID- 4034207 TI - Hypogammaglobulinemia arthritis--case report. PMID- 4034208 TI - [Prognosis of birth injury-induced paralysis of the brachial plexus]. PMID- 4034209 TI - [Esophageal pressure measurements in newborn infants within the scope of respiratory mechanical studies]. PMID- 4034210 TI - [Possibilities of organ preservation in splenic rupture]. PMID- 4034211 TI - [Immunological and clinical studies on the detection of immune reactivity in childhood with special reference to selected disease groups. 3. Immunologic studies in patients with kidney diseases]. PMID- 4034212 TI - [Kinetic determination of exocrine arginine esterase enzyme activity in mixed saliva and serum of heterozygous in mucoviscidosis in comparison to controls]. PMID- 4034213 TI - Abnormal electrophoretic mobility of erythrocytes in cystic fibrosis: evidence for a membrane defect. PMID- 4034214 TI - [Mechanism of a genetically conditioned failure to thrive shown in a patient with ring chromosome 18]. AB - The influence of genetic factors on growth is only partially understood. The assumed regulatory mechanism is an interplay of multiple genes, which are localized on various chromosomes. Numerical and unbalanced structural chromosome anomalies cause abundance or lack of genes and gene products. As a consequence the subtle, in their complexity hardly fully conceivable regulatory mechanisms for metabolism and growth of the single cells appear to be disturbed. This kind of model is supported by the occurrence of growth failure in most numerical and structural chromosome anomalies. Further evidence is the variability of the phenotype in cases of ringchromosome 18, which depends on the localization and degree of loss of chromosome material preceding ring formation: depending on the participation of one or several growth-regulating genes normal or impaired growth follows. Consequently we find some normally thrived proponents within the group of predominantly mal grown people with ringchromosome 18. Besides growth the phenotypical variability is concerned with a whole lot of body-functions and systems and virtually every case reported in the literature shows individual signs. This is also true for the patient reported in this paper, in whom we additionally describe the following hitherto not mentioned signs: rudimentary pair of first ribs, apical pulmonary hernias, submammilary dermal groove, hemangioma, meatal stenosis of the urethra, unilateral kidney aplasia, 6 lumber vertebral bodies, umbilical-, abdominal- and inguinal hernias. PMID- 4034215 TI - [The Schwartz-Bartter syndrome]. AB - Nine children with Schwartz-Bartter-syndrome are described. Seven suffered from severe diseases of the CNS, 2 developed the syndrome during treatment with vincristine, the damaging action of which on the CNS is known. The main symptoms of the syndrome are: hyponatremia with consecutive hypotonia of the extracellular space caused by excessive urinary sodium loss. The plasma volume is not diminished. Therapeutically administered NaCl appears in the urine which is hyperosmolar in spite of the hypoosmolarity of the plasma. The increased secretion of ADH which Schwartz et al. postulated to be the cause of the syndrome has been confirmed in recent years. The organism attempts to excrete the increased fluid volume which is retained by ADH, probably by means of a natriuretic hormone, so-called third factor. Enhanced activity of such a factor was assessed in one of our cases. PMID- 4034216 TI - [Determination of chymotrypsin in the feces by a new photometric method]. AB - Fecal chymotrypsin (FCT) was determined in stool specimens of healthy children and those with gastro-intestinal disease, by a new photometric method. The values are comparable with chymotrypsin concentrations found by pH-stat method. The new test is cheap, reliable and easy to perform. For this reasons and for the sensitivity of all tubeless pancreatic function tests (NBT-PABA, FDL, FCT) is rather low (60-70%), the FCT-test may be preferred as diagnostic marker for differential diagnosis of exocrine pancreatic insufficiency. PMID- 4034217 TI - [Pyruvate kinase deficiency in the newborn infant]. AB - 4 cases with haemolytic anemia associated with pyruvate kinase deficiency from 3 different families are presented. Different clinical development during the first year of life is demonstrated and discussed. PMID- 4034218 TI - [High intracranial pressure with the spreading of the cranial sutures as a leading symptom of herpes simplex meningitis]. AB - A four-year old girl developed signs of increased intracranial pressure (head ache, vomiting, ataxia, tremor, papilledema, cranial suture spread). Abacterial meningoencephalitis due to herpes virus was diagnosed, while the initially suspected brain tumor was ruled out. Without specific therapy the patient recovered completely; even the cranial suture spread disappeared. This case report demonstrates an unusual and more benign course of central nervous herpes virus infection. PMID- 4034219 TI - [Glycine encephalopathy: a non-ketotic disorder of glycine catabolism]. AB - We report on a newborn with peracute glycine encephalopathy. The child exhibited poor feeding, incipient respiratory failure and increasing muscular hypotonia from the first few days of life onwards and was admitted to hospital at six weeks due to regression of the symptoms. Following respiratory arrest the child had to be placed on controlled ventilation and died at the age of four months in spite of therapeutic measures. Previous papers on this rare disease have described elevated CSF glycine levels, EEG patterns, CT scan and acoustic and visual evoked potentials. We have supplemented these for the first time by somatosensory evoked potentials. The following is an account of the clinical course and the therapy given. PMID- 4034220 TI - [Cefaclor in the treatment of respiratory tract infections in children]. AB - 61 children up to the age of 14 years with respiratory tract infections underwent therapy with Cefaclor. 52 patients (89%) had satisfactory results. 4 patients (7%) experienced prolonged signs of infection. Cefaclor was very well tolerated. Because of its wide spectrum of activity particularly against ampicillin resistant strains of H. influenzae and because of its good tolerance Cefaclor is very useful in treatment of respiratory tract infections in children. PMID- 4034221 TI - [Current therapeutic problems in the treatment of infectious diarrheal diseases in children]. AB - 82 children, not older than 2 years, with enteritis are divided in two groups. Fluid- and electrolyte therapy is the same in both groups. In one group the usual antibiotic treatment was given, the other group get a combination drug: metabolic substances of physiologic enteric bacteria and a sulfonamide with very low absorption rate. The efficiency is nearly the same in both groups. In regard to the side effects of antibiotic therapy, it seems necessary to give preference to this compound drug. PMID- 4034222 TI - Tooth pulp-evoked potentials in the monkey: cortical surface and intracortical distribution. AB - The distribution of tooth pulp-evoked potentials (TPEPs) was characterized in the primary motor (MI), primary somatosensory (SI) and secondary somatosensory (SII) cortices of the monkey. Bipolar electrical tooth pulp stimulation elicited TPEP components P23 and N44 over SI, P26 and N72 over MI, and P72, N161, P280, N420, P561 and N662 over SII. Muscular artifacts and extradental input did not affect the TPEP as demonstrated by experiments using a neuromuscular blocking agent and removal of the pulp, respectively. The short latency TPEPs recorded over SI and MI were evoked by low stimulus intensities and activation of A beta nerve fibers, whereas the long latency TPEPs recorded over SII required higher stimulus intensities and the additional recruitment of A delta nerve fibers. Intracortical recordings revealed polarity reversals of components P23 and N44 in area 3b, P26 and N72 in area 4, and P72, N161, P280, N420, P561 and N662 in the upper bank of the lateral sulcus (SII). Evidence presented in this study suggests that TPEPs recorded from SI and MI relate to non-nociceptive mechanisms while TPEPs recorded from SII relate to nociceptive mechanisms. PMID- 4034223 TI - Psychosocial predictors of labor pain. AB - The relationship between labor pain and concomitant psychological state, in terms of prenatal anxiety levels and post-partum mood, has been studied. A consecutive series of primiparae (n = 129) was assessed at intervals over the course of their pregnancy and after delivery. State anxiety was measured at recruitment (10-14 weeks of pregnancy), 10 weeks, 32 weeks and at labor. Labor pain was assessed on the McGill Pain Questionnaire (MPQ) and visual analog rating scales. Pain ratings on the MPQ were found to be high when compared to other clinical pain groups. Drug use in labor emerged as the strongest predictor of pain ratings on the MPQ total, sensory and affective scales, accounting for 11, 9 and 7% of the variance respectively. Anxiety scores at 32 weeks accounted for a further 5% of the variance and emerged as the best predictor of MPQ evaluative scores and visual analog ratings. A significant association was found between pain ratings and ratings of post-partum mood. Neither attendance at preparatory classes nor initial attitudes towards the neonate were related to pain scores. PMID- 4034224 TI - Success in surgery may not require cutting the tracts. AB - Two patients are described in whom surgical intervention was terminated prior to the lesioning of any pathways relevant to pain and yet the surgery relieved the chronic severe pain. PMID- 4034225 TI - Use of extraanatomical procedures in vascular surgery. PMID- 4034226 TI - Vascular impotence: therapeutic procedures of penile revascularization. PMID- 4034227 TI - Extracellular and muscle electrolytes and acid-base status in urinary diversion. PMID- 4034228 TI - Prolactin and TSH response to alpha-methyl-l-tyrosine in normal subjects and in women with pathological hyperprolactinemia. PMID- 4034229 TI - Vectorcardiographic abnormalities in severe obesity. PMID- 4034230 TI - Serum ferritin concentration in malignant lymphomas. PMID- 4034231 TI - Infrared and ELC thermography in the assessment of the digital rewarming curve after a Finger-Cooling test. A preliminary report. PMID- 4034232 TI - The treatment of postoperative pain with the use of semipermanent auricular needles. PMID- 4034234 TI - Effect of pre-anesthetic medications on serum lipid levels. PMID- 4034233 TI - Ascites with suprahepatic portal hypertension in a case of Behcet's disease. PMID- 4034235 TI - Haemostatic balance and thrombotic tendency after extracorporeal circulation. PMID- 4034236 TI - The serum antibody response of infected rats, rabbits, lambs and calves to Fasciola hepatica adult antigen fractions separated by preparative flatbed iso electrofocusing. AB - Electrofocusing of F. hepatica adult antigen in granulated gels separated the material into 22 arbitrary fractions. Polyacrylamide gel analysis demonstrated groups of proteins with similar iso-electric points in 19 of the fractions. A microplate ELISA detected antigens in all 22 fractions and was used to test the serum antibody response in infected rats, rabbits, lambs and calves to these antigen fractions. The results indicated that rat and calf sera gave a much stronger response than rabbit and lamb sera to the antigens which separated above pH 7.0. It is possible that the greater efficiency of the rat and bovine immune systems in combating re-infection with F. hepatica may be related to this response. PMID- 4034237 TI - Immunopathology of Schistosoma japonicum infection in athymic mice. AB - Athymic (nu/nu) mice and heterozygous littermate controls (nu/+) were examined 7 and 10 weeks after infection with 10 cercariae of Schistosoma japonicum. Schistosome infection developed normally in both groups of mice and eggs were produced in normal numbers. Nu/nu mice developed small circumoval granulomas with minimal fibrosis while nu/+ mice developed large fibrotic granulomas. Unlike the mononuclear responses to S. mansoni eggs at 7 weeks, those to S. japonicum often were abscess like with narrow rims of liver cell necrosis or microvesicular fatty change. However, evolving granulomas in nu/+ mice were enriched with eosinophils, epithelioid macrophages, immature granulocytes and plasma cells, all scarce in the corresponding nu/nu lesions as were fibroblasts and collagen fibres, thus accounting for their smaller mean size and better healing. Our aggregate evidence shows that normal granuloma formation and cellularity in S. japonicum infection is controlled by T-cells as is the case for S. mansoni, and not by antibodies or immune complexes. PMID- 4034238 TI - Immunosuppression associated with visceral leishmaniasis of hamsters. AB - Immunosuppression was demonstrated during the course of Leishmania donovani infection of outbred and inbred hamsters. Proliferative responses of splenic lymphocytes to the mitogen concanavalin A (Con A) and to promastigote antigens were used as indicators of immune responsiveness. Although splenic lymphocyte proliferative responses to parasite antigens were demonstrable 3 weeks after challenge, antigen specific lymphocyte responses diminished as the infection progressed. Two types of immunosuppression were demonstrable. The first was a non specific anergy of splenic lymphocytes to Con A stimulation. Thus, spleen cells from infected animals did not actively suppress the Con A responses of normal lymphocytes in mixed cultures A second immunosuppression mechanism, specific for leishmania antigens was mediated by a nylon wool non-adherent cell population. The suppressor, tentatively identified as a T cell population, inhibited the proliferation of parasite antigen sensitized responder lymphocytes in mixed culture. Elimination of the parasite burden by glucantime therapy restored responsiveness of lymphocytes to parasite antigens. Con A responses, however, remained suppressed 1 week after drug cure. PMID- 4034239 TI - A rapid chromatographic method for elimination of fungal contamination in in vitro cultures of Leishmania spp. AB - It was demonstrated that antimycotic agents are unsuitable for elimination of mycotic contamination in in vitro cultures of Leishmania spp. Ion-exchange chromatography was designed to separate the protozoan parasites from the contaminating yeast or fungal cells based on their surface net charges. The method was found to be efficient and rapid, and would also reduce bacterial contamination in cultures which have been exposed to both contaminants. Viability of the cells has been shown to be unaltered by this treatment as demonstrated by their ability to multiply rapidly in culture medium, as was seen in the controls. PMID- 4034240 TI - An ultrastructural examination of irradiated, immunizing schistosomula of Schistosoma mansoni during their extended stay in the lungs. AB - An ultrastructural study has been performed on radiation-attenuated parasites fixed in situ during their extended stay in the lungs. At day 7 post-infection all parasites were located within blood vessels. In contrast to normally migrating parasites, at days 13 and 21 post-infection the majority of radiation attenuated parasites were lying free within alveoli. As far as could be seen, radiation-attenuated parasites had undergone the normal developmental changes associated with the lung stage of migration. These included elongation of the body and loss of mid-body spines and the fibrous layer beneath the tegument. No ultrastructural evidence was found to suggest why schistosomula failed to migrate further and instead burst into alveoli. No parasites observed on day 7 post infection were associated with a host inflammatory reaction. At day 13, inflammation was noticeable but could have been a response as much to pulmonary tissue damage as to the presence of parasites. At day 21 post-infection some parasites were internally disrupted but were not associated with host inflammatory reactions and had intact tegumental surfaces - all facts consistent with death by autophagy. One parasite was observed at day 21 with an adherent neutrophil infiltrate and extensive tegumental damage. The relevance of persisting lung-stage parasites to the induction of resistance to challenge is discussed. PMID- 4034241 TI - Schistosoma mansoni: an ultrastructural examination of skin migration in the hamster cheek pouch. AB - The hamster cheek pouch has been used to investigate the skin migration of schistosomula at the ultrastructural level. Parasites have been observed up to 72 h post-infection. Despite rapidly reaching the epidermal basement membrane schistosomula remain in an epidermal location for at least 40 h post-infection, by which time the acetabular glands and their ducts have been lost and the transformation from cercaria to schistosomulum completed. Entry into the dermis and exit from the skin via the blood vessels is therefore by mechanical means or by lytic secretions emanating from a source other than the acetabular glands. The head gland which persists in the dermal schistosomula is a probable source of such secretions. The observations suggest that the apical area and musculature of the head capsule are important in gaining access to the lumen of blood vessels. PMID- 4034242 TI - The metabolism of xenobiotic compounds by Hymenolepis diminuta (Cestoda: Cyclophyllidea). AB - The hydrolytic, reductive and oxidative enzyme systems involved in the phase I biotransformation of xenobiotic compounds have been investigated in Hymenolepis diminuta. Adult H. diminuta are able to carry out a range of hydrolytic and reductive reactions, but in common with other helminths oxidative detoxification reactions were absent (oxidative demethylation, aniline hydroxylation, nitrobenzene hydroxylation, biphenyl hydroxylation). These oxidative reactions were readily demonstrated in rat liver. Extracts of H. diminuta hydrolysed nitrophenylphosphates and inorganic pyrophosphate, but not arylsulphates, nor could epoxide hydratase activity be detected. N-Deacetylase activity was present. However, O-deacetylase activity could not be demonstrated, although butyrate and palmitate, but not benzoate, esters were hydrolysed. H. diminuta was capable of hydrolysing a range of alpha-and beta-glycosides, but not beta-glucuronides. Extracts of H. diminuta reduced azo-compounds, aldehydes and disulphides, but ketones and aromatic nitro-compounds were not reduced. The phase I detoxification systems of H. diminuta differ considerably from those of its rat host; the results also suggest that, within the cestodes, there may be considerable species variation in detoxification reactions. PMID- 4034243 TI - Dose-dependent relationships between Nippostrongylus brasiliensis populations and rat food intake. AB - The pattern of daily food intake of well-nourished rats infected with Nippostrongylus brasiliensis included 2 distinct phases when food intake was much less than that of uninfected controls (days 0-4 and days 6-10 p.i.). These phases were separated by a period (days 4-6) of still reduced but relatively constant food intake. From day 10 p.i. food intake increased so that between days 12 and 17 infected rats ate more than uninfected controls. In each of the phases of reduced food intake there was a threshold dose above which food intake was further decreased as dose increased. In contrast to the obvious relationship between food intake and dose, food intake could not easily be related to the size of the adult Nippostrongylus population, as judged by egg and worm counts. The relationship appears to be complicated by host variability in susceptibility to infection and to the pathological effects of infection. Effects of N. brasiliensis on the daily pattern of food intake can be explained with respect to stages in the development of the parasite and host responses directed against the adult worms. PMID- 4034244 TI - The effect of host density on the establishment and fecundity of Heligmosomoides polygyrus. AB - The effect of mouse population density on the establishment, survival and fecundity of single cohorts of Heligmosomoides polygyrus was investigated. No significant relationship was found between host population density and the worm burden at post mortem. But, lower host population densities were associated with higher parasite fecundities and with higher overall mean daily faecal output. The results might be explained by a decrease in male hormone secretion or digestive disturbances associated with lower ingesta in the higher host population densities. Effects resulting from changes in immunological responses might also exist. PMID- 4034245 TI - Morphological effects of arprinocid on developmental stages of Eimeria tenella and E. brunetti. AB - Medication of chicks with 70 p.p.m. arprinocid in the food, starting 2 days prior to inoculation with Eimeria tenella, resulted in decreased oocyst production and oocyst sporulation. The main morphological alteration seen during the development of the second-generation schizont was a reduction in the number of second generation merozoites due to incomplete merogony, resulting in large masses of vacuolated residual cytoplasm. In places around the developing macrogamete the integrity of the parasitophorous vacuole was lost by either the host cell limiting membrane making contact with the parasite pellicle, or the disruption of one or both of these surfaces apparently brought about by the intervention of the host cell mitochondria. Thirty p.p.m. arprinocid reduced sporulation of the oocysts of E. brunetti and caused enlargement of the perinuclear space in the late merozoites and swelling of the endoplasmic reticulum around wall-forming bodies II. PMID- 4034246 TI - Pathogenicity of the coccidium Eimeria crandallis in laboratory lambs. AB - Ten colostrum-deprived, coccidia-free lambs were reared artificially in indoor cages. At 4 weeks of age they were allocated to 5 groups of 2: Groups 1-3 received 10(4), 10(5) and 10(6) sporulated oocysts of Eimeria crandallis/lamb respectively, each as a single inoculum. Group 4 lambs received daily doses increasing over a 4-week period. Groups 1-3 showed diarrhoea and weight loss from about day 14, followed by slow recovery from about day 30. The diarrhoea was accompanied by a wave of oocyst output and a reduction in serum albumin and plasma alkaline phosphatase activity. One lamb in group 4 died of an unrelated condition on day 15; the other showed no clinical effect of the oocyst inoculations and its oocyst output was related only to the first week or two of inoculation. Lambs in Group 1 showed no clinical effect or oocyst output following challenge with 10(6) oocysts on day 28. E. crandallis showed high pathogenicity and immunogenicity. Its pathogenicity was not closely related to infecting dose within the range 10(4)-10(6). PMID- 4034247 TI - Suppression of Trypanosoma congolense, T. vivax and T. brucei infection rates in tsetse flies maintained on goats immunized with uncoated forms of trypanosomes grown in vitro. AB - Significant suppression in the incidence of cyclical development of Trypanosoma congolense, T. vivax and T. brucei occurred in Glossina morsitans centralis maintained on goats immunized with in vitro-propagated uncoated forms of T. congolense, T. vivax and T. brucei, respectively. This was observed when tsetse given a T. congolense-infected feed were subsequently maintained on uninfected immunized goats and also when uninfected tsetse were fed on immunized goats infected with T. congolense, T. vivax and T. brucei. Suppression of infection rates in tsetse was trypanosome species specific, but was independent of the trypanosome stock used for immunization of goats. These findings were reflected in antibody responses to uncoated trypanosomes, as measured by immunofluorescence and the solid-phase immunoradiometric binding assay. Thus, antibody from goats immunized with uncoated trypanosomes of one species exhibited minimal reactivity with uncoated forms of other species of trypanosomes, but showed high levels of activity with uncoated forms of the same or unrelated stocks of the same species. However, in view of the range of hosts upon which tsetse feed, it is open to question whether the use of a vaccine which suppresses trypanosome infection rates in tsetse would have any significant effect in the field. PMID- 4034248 TI - Changes in the surface antigen profile of Schistosoma mansoni during maturation from cercaria to adult worm. AB - Antigenic proteins on the surfaces of different developmental stages of Schistosoma mansoni were radio-iodinated by the Iodogen-catalysed method and identified by immunoprecipitation with a panel of antisera. The sera comprised specific immune serum from mice harbouring a chronic schistosome infection or vaccinated with gamma-irradiated cercariae; serum from rabbits immunized with adult schistosome tegumental outer membranes or a partially purified Mr 32 K glycoprotein from adult worm membranes; and a monoclonal antibody recognizing an Mr 20 K antigen on the surface of schistosomula. The Mr 38-32 K glycoproteins were the major antigens identified in surface-labelled cercariae and their probable association with the glycocalyx is discussed. Schistosomula transformed from cercariae either mechanically or by penetration of host skin in vitro, expressed a similar pattern of surface antigens to that identified for cercariae, but low molecular weight antigens of Mr 20, 17 and 15 K were also detected. The Mr 38-32 K glycoproteins, although present on newly transformed schistosomula, were progressively replaced with time, by a single dominant glycoprotein (Mr 32 K) expressing identical epitopes to those on the Mr 38-32 K complex. Moreover, the data confirm that the Mr 32 K glycoprotein persists on the tegument after in vivo maturation and is conserved, together with Mr 20 and 15 K antigens, through to the adult stage. New antigens (Mr 97 and 25 K) were also detected during in vivo maturation and were present in late-stage schistosomes recovered from infected hosts. In addition, the enzyme alkaline phosphatase is expressed on the surfaces of 3-week-old liver worms as a dominant antigen (Mr 65 K); this feature may be related to nutritional and/or physiological processes in the tegument of this metabolically active stage of development. PMID- 4034249 TI - [Effect of hyperlipoproteinemia on the Ca2+ content in subcellular fractions of the myocardium]. PMID- 4034250 TI - [Effectiveness of the combined use of antioxidants and nucleic acid precursors in experimental myocardial infarct]. PMID- 4034251 TI - [Level of lipolysis and the contractile function of the intact myocardium]. PMID- 4034252 TI - [Myocardial metabolism in experimental uremia]. PMID- 4034253 TI - [The human problem in philosophy and medicine and the ideological struggle]. PMID- 4034254 TI - [Mechanism of different degrees of resistance of the heart and kidneys to the action of thermal ischemia]. PMID- 4034255 TI - [Functional importance of the right atrial terminal crest in damage to the sinoatrial node]. PMID- 4034256 TI - [Electrocardiographic changes during the modelling of Lutembacher's syndrome]. PMID- 4034257 TI - [Characteristics of the ventilatory function and x-ray picture of the lungs in progressive bronchial obstruction]. PMID- 4034258 TI - [Pathogenetic aspects of papain-induced pulmonary emphysema in rabbits]. PMID- 4034259 TI - [Effect of vagotomy on the epitheliocytes of the pyloric and duodenal glands]. PMID- 4034260 TI - [Role of intrauterine hypoxia in the occurrence of neurotic states in the developing rat]. PMID- 4034261 TI - [Effect of the separate and combined use of fentanyl and droperidol on animal sensitivity to hypoxia]. PMID- 4034262 TI - The borderline hypertensive rat (BHR): a new model for the study of environmental factors in the development of hypertension. AB - While many studies have attempted to produce hypertension through the use of various environmental stressors, few have succeeded in producing chronic elevations in blood pressure beyond levels considered to be borderline hypertensive (140-160 mm Hg systolic). The problem with most studies stems from the use of genetically normotensive animals and the selection of stressors to which animals readily adapt. A new approach is suggested, which recognizes the role of genetics in human essential hypertension. Animals with one hypertensive parent do not develop spontaneous hypertension but show a more sensitive cardiovascular response to environmental stressors than animals with normotensive parents. Preliminary studies revealed that animals with a mixed genetic history of hypertension develop spontaneous borderline hypertension. When subjected to shock-shock conflict, these borderline hypertensive rats (BHR) developed permanent hypertension that failed to abate even after a ten-week, shock-free recovery period. The hypertension was accompanied by elevated heart weight to body weight ratios and by significant cardiac pathology. Subsequent work has demonstrated that these animals also become hypertensive when fed a high-sodium diet. Finally, in a series of exercise studies, we found that BHRs subjected to a shock stressor were protected against stress-induced hypertension if they exercised daily. The potential of this model for studies of the mechanisms by which environmental variables produce permanent hypertension is discussed. PMID- 4034263 TI - Intracerebral scopolamine administration attenuates Pavlovian heart rate conditioning in the rabbit. AB - Scopolamine hydrobromide was injected into the septum, dorsal hippocampus, or lateral ventricles of conscious rabbits via bilateral chronic indwelling cannulas. The cardiac orienting reflex (OR) and heart rate (HR) classical conditioning were assessed. A fourth group of animals received injections of the vehicle solution into these same brain areas and were otherwise similarly trained. Scopolamine had no effect on the cardiac OR produced by unreinforced tone stimuli. The OR consisted of pronounced bradycardia that habituated over successive trials in all groups. The HR change during classical conditioning also consisted of bradycardia. However, these conditional HR changes were attenuated by scopolamine injected into the septum and lateral ventricles, but were not affected by injections into the dorsal hippocampus. These results suggest that centrally applied scopolamine may affect a central nervous system associative process, and not a mechanism directly involved in primary bradycardia. PMID- 4034264 TI - Contextual stimulus control of conditional vasomotor and electrodermal reactions to angry and friendly faces. Transswitching--yes! Preparedness--No! AB - An experiment with 42 human Ss used the transswitching procedure to examine tonic stimulus control of phasic and tonic conditioned vasomotor heart rate, and electrodermal reactions. The conditional stimulus (CSs) were photos of angry and friendly human faces, and the unconditional stimulus (US) was a human scream. In one tonic context (blue light), the CSs were paired with the US, in the other context (yellow light), the CSs were presented unpaired. Following acquisition, an extinction series was run with the US omitted during both tonic contexts. Phasic vasomotor and skin conductance reactions differed in the positive and negative tonic segments (stronger in positive). The skin conductance responses also differed during extinction, but the vasomotor responses did not. Tonic differences (following onset of the tonic stimuli) in unelicited skin conductance response frequency, finger pulse volume, and heart rate were also found, although these developed more slowly than the phasic differences. The finger pulse volume tonic difference was greater in extinction than the skin conductance response frequency. There was no effect of the angry-friendly facial expressions, either directly or in interaction with the transswitching effects. The results were interpreted to mean that the transswitching phenomenon is not limited to one another autonomic effector, but is more generalized across the ANS (sympathetic branch). The absence of influence of the facial expressions indicates the relative weakness of the "preparedness" hypothesis in comparison with more influential contextual factors. PMID- 4034265 TI - A functional analysis of social reinforcement in vicarious verbal conditioning. AB - This article reports the results of 629 subjects in three experiments designed to replicate and extend the phenomenon of vicarious verbal conditioning. Experiment I replicated the finding that subjects who responded most to vicarious verbal conditioning were aware of the contingency involved. Experiment II attempted to examine the effects of prior history with the verbal reinforcer on vicarious verbal conditioning by providing seven groups of subjects with varying classic conditioning histories prior to vicarious verbal conditioning. The null results associated with this experiment were hypothesized to be due to the fact that the vicarious verbal conditioning took place in a language laboratory where the subjects could hear but not see the model. Experiment III replicated Experiment II in a live group context as was done in Experiment I. The results showed that vicarious verbal conditioning was again found to take place, that associating the verbal reinforcer with a tone or tone plus money via forward classic conditioning potentiated the effects of the verbal reinforcer, that backward classic conditioning did not potentiate the reinforcer, d) nor did either of two sensitization procedures potentiate the effects of the verbal reinforcer. Both aware and unaware subjects evidenced vicarious verbal conditioning. PMID- 4034266 TI - Stress and child health: an overview. PMID- 4034268 TI - Social support and vulnerability to stress: a pediatric perspective. PMID- 4034267 TI - Stress, coping and children's health. PMID- 4034269 TI - Psychological distress and children's use of health services. PMID- 4034270 TI - Biological mechanisms in the relationship of stress to illness. PMID- 4034271 TI - Symposium on pediatric surgery. PMID- 4034272 TI - Trauma in infancy and childhood: initial evaluation and management. AB - Successful management of the critically injured multiple trauma patient frequently depends on the expertise of the first physician contracted. Thus, this article outlines a systematic approach to the assessment and resuscitation of pediatric trauma victims. PMID- 4034273 TI - Radiographic-endoscopic correlations in the examination of airway disease in children. AB - The results of radiographic examinations and flexible fiberoptic endoscopy (FFE) of the airways were correlated in 100 pediatric patients. For the diagnosis of laryngomalacia, tracheal stenosis and tracheal granulomas. FFE proved to be more accurate than radiography. In epiglottitis and croup, the two methods were comparable. In bronchial and resulting parenchymal disease, the chest films served as the endoscopist's guide because the consequences of bronchial obstruction manifested rapidly on chest roentgenograms. FFE was particularly useful when the chest films did not reveal or lateralize a clinically suspected foreign body. FFE was not error-free; in a small number of cases, radiologic methods provided critical diagnoses, which were not arrived at by endoscopy. PMID- 4034274 TI - Chest radiographs of near-drowned children. AB - From 1972 through 1983 there were 10 near-drowned children (7 boys and 3 girls) aged 1 to 4 years, treated as inpatients at the Children's Hospital of the Medical Academy Dresden. Three of them showed a severe aspiration pneumonia which in one case was complicated by bilateral pneumothoraces. In a further five children there were radiological signs of pulmonary oedema. Only in two children were the X-ray pictures of the chest normal. PMID- 4034275 TI - Derangement of swallowing in children with myelomeningocele. AB - Barium esophagrams performed in 13 children with myelomeningocele demonstrated a variety of swallowing disorders: difficulty in bolus formation, nasopharyngeal reflux, tracheobronchial aspiration. Cricopharyngeal spasm was not identified in this group. Antegrade peristalsis in the distal two-thirds of the esophagus was normal. Gastroesophageal reflux was demonstrated in 8 of the children. Vocal cord paralysis (8/13) and death in early children (7/13) occurred with greater frequency than in the general myelomeningocele population. Correct management of these children may require tracheostomy, gastrostomy, and fundoplication. PMID- 4034276 TI - The nuclear magnetic resonance appearances of neuroblastoma. AB - In addition to being a non-ionising method of imaging, nuclear magnetic resonance has the ability to demonstrate the body organ using different radio pulse sequences in order to highlight different tissues. Neuroblastomas are best demonstrated using proton spin lattice relaxation time (T1) weighted images such as inversion recovery or calculated T1, rather than proton density. The ability to produce sections in the sagittal and coronal as well as the axial plane allows for accurate tumour localisation and management planning. The appearances of primary neuroblastoma and metastatic spread to bone are described in three cases of neuroblastoma. PMID- 4034277 TI - Intracranial teratoma associated with agenesis of the corpus callosum. AB - Several intracranial tumors are known to occur in conjunction with agenesis of the corpus callosum. We report the occurrence of a teratoma with callosal agenesis, an association not previously described, and suggest that the tumor's ventral location may serve to differentiate it from other lesions. PMID- 4034279 TI - Dystrophic calcification in obliterated umbilical artery. AB - Evidence is presented that calcification may occur within the horizontal pelvic portion of the obliterated umbilical artery and that the finding may be visible on abdominal radiographs. PMID- 4034278 TI - Pulmonary sequestration with congenital gastroesophageal communication. Report of two cases. AB - Two children with pulmonary sequestration and gastroesophageal connections are described. Barium studies demonstrated the site of the connection and angiography showed the vascular connections enabling successful surgery to the performed. PMID- 4034280 TI - Premature sternal fusion in gonadal dysgenesis with coarctation. AB - Gonadal dysgenesis and coarctation of the aorta were found in four patients to be associated with premature sternal fusion but possible etiologic relationship to shield chest deformity in suggested. PMID- 4034281 TI - Uses of the case-control and cohort epidemiological approaches in pediatric practice and research. AB - Increasing reliance is being placed on the use of quantitative epidemiological methods in the conduct and evaluation of pediatric research. The basic design features of two common types of observational studies, the case-control study and the cohort study, are reviewed. Advantages and disadvantages of these two study designs are discussed with emphasis on aspects such as the selection of comparison groups, avoiding selection and recall bias, gathering exposure information, controlling for potentially confounding factors, and methods of analysis. Appreciation of the salient features of these study design approaches should aid the clinician/researcher in the conduct of research endeavors as well as in critically reviewing the medical literature. PMID- 4034282 TI - Effect of dietary calcium on metabolic balance of normal infants. AB - Metabolic balance studies were performed with six normal infants fed in a balanced cross-over design three formulas differing only in calcium concentration: 389, 659, and 1024 mg/liter. Absorption of phosphorus was significantly affected by increasing calcium intake decreasing from 68 to 63 to 52% of intake. However, since urinary excretion of phosphorus also decreased, there was no significant effect on retention of phosphorus. Absorption of fat was slightly (but significantly) depressed by calcium, decreasing from 97.5 to 95.5 to 92.1% as calcium intake increased. The level of dietary calcium had no significant effect on absorption or retention of nitrogen, magnesium, copper, and zinc. One of the subjects had consistently lower absorption of calcium and fat than the other subjects, suggesting an absorptive defect. The decrease in fractional absorption of calcium (57 to 47 to 39% of intake) with increasing intake of calcium is compatible with adaptive regulation. On the other hand, the observation that absorbed calcium (mg/kg/day) was linearly related to intake of calcium with a slope of 0.373 suggests an alternative explanation: constant passive, concentration-dependent (slope), and constant active (y-intercept) transport of calcium over the range of calcium intakes. Thus, the findings are explainable in more than one way and do not necessarily demonstrate regulatory changes. PMID- 4034283 TI - Electrodermal potential and conductance measurements clinically discriminate between cystic fibrosis and control patients. AB - To evaluate the adaptation of electrodermal techniques for cystic fibrosis screening, skin surface bioelectric measurements were recorded from 37 established cystic fibrosis patients, 45 asthmatic patients, and 10 normal controls, ranging in age from 6 to 22 yr. Six skin potential and six skin conductance measures of sweat gland activity without the collection of sweat distinguished between the cystic fibrosis, normal, and asthmatic groups (F ratios greater than 10.0; p less than 0.0001). Discriminant analysis using the two best electrodermal measures (the mean of five preresponse potential levels and the mean of five preresponse conductance levels for each subject) to assign experimental group membership matched actual group membership with 92.7% accuracy. We believe these results warrant further investigation of electrodermal procedures as a direct, simple, yet noninvasive means of screening for cystic fibrosis. PMID- 4034284 TI - The responses of glutathione and antioxidant enzymes to hyperoxia in developing lung. AB - Total glutathione levels and the activity of enzymes associated with antioxidant protection in neonatal lung are increased in response to hyperoxia. Glutathione levels in developing rat lung decreased from 24 nmol/mg protein on day 19 of gestation to approximately 12 nmol/mg protein at birth. The initial decrease in glutathione may be due to emergence of other antioxidant systems. Newborn rats placed in 100% oxygen showed a rapid and sustained increase in total glutathione levels which was primarily due to an increase in reduced glutathione. Explants obtained from 16-wk gestation human fetal lung or from 17- to 18-day fetal rat lung also showed increased total and reduced glutathione when cultured in 95% oxygen, 5% CO2 as compared with explants cultured in room air. Type II cells isolated from neonatal rats maintained in oxygen for 6 days also showed glutathione levels twice those found in cells isolated from animals in room air. The activity of antioxidant enzymes (glucose-6-phosphate dehydrogenase, glutathione peroxidase, glutathione reductase) was increased in lungs of newborn rats exposed to 100% oxygen either at birth or 2 days of age. Antioxidant enzyme activity of lung explants cultured in 95% oxygen, 5% CO2 was also higher than in explants maintained in room air. These results suggest that the increases in glutathione and of antioxidant enzymes in vivo and in vitro are a direct effect of oxygen exposure in lung and that the increase of both glutathione and antioxidant enzyme activity is intrinsic to the lung cell itself. It is likely that increases in glutathione in lung represent an important protective mechanism against oxidant injury. PMID- 4034285 TI - Effect of supernatants from nephrotic peripheral blood mononuclear cells on 35sulfate incorporation in rat glomerular basement membrane. AB - In previous research, we showed that when peripheral blood mononuclear cells (PBMC) from patients with idiopathic minimal lesion nephrotic syndrome (IMLNS) in relapse were cocultured with rat glomeruli, there was an increased glomerular basement membrane (GBM) uptake of 35sulfate. This study was done to determine whether the increased uptake was due to substances secreted into the nephrotic PBMC culture supernatants. 35sulfate uptake in rat GBM was significantly higher when glomeruli were cocultured with PBMC from 12 IMLNS patients in relapse (geometric mean [GM] = 513 cpm/mg) than when simultaneous assays were done using either PBMC from eight control subjects (GM = 158) (p less than 0.05) or glomeruli incubated without PBMC (GM = 275 cpm/mg) (p less than 0.01). 35sulfate uptake did not increase when glomeruli were cocultured with PBMCs from 11 MLNS patients in remission. Rat GBM 35sulfate uptake was significantly higher when glomeruli were incubated in the supernatants of the PBMC cultures from 16 IMLNS patients in relapse (GM = 234 cpm/mg) than it was when glomeruli were cultured in the supernatants from normal control PBMC (GM = 141 cpm/mg; p less than 0.002) or from glomeruli cultured alone (GM = 141 cpm/mg) (p less than 0.04). Supernatants from PBMC cultures of 11 IMLNS patients in remission did not increase rat GBM 35sulfate uptake. These data suggest that PBMC from IMLNS patients in relapse secrete a factor(s) released into supernatants that increases the 35sulfate rat GBM uptake. Since sulfated compounds in the GBM play a role in glomerular permeability, this finding may have pathogenic significance. PMID- 4034286 TI - Metabolic quotients of the gravid uterus of the chronically catheterized guinea pig. AB - The uptake of substrates by the pregnant uterus defines the "diet" of the uterus and conceptus. In order to determine the uterine substrate uptake, catheters were placed in the femoral artery and uterine veins of guinea pigs at 40-49 days gestation. After at least 2 days recovery from perioperative stress, systemic arterial and uterine venous concentrations of oxygen, glucose, lactate, acetoacetate, beta-hydroxybutyrate, acetate, and free fatty acids were measured and metabolic quotients were calculated. The glucose/O2 quotient was 1.22 +/- 0.07 (mean +/- SEM), the lactate/O2 quotient was -0.40 +/- 0.09, the acetoacetate/O2 quotient was 0.03 +/- 0.02, the beta-hydroxybutyrate/O2 quotient was 0.01 +/- 0.006, the acetate/O2 quotient was 0.03 +/- 0.01, and the free fatty acid/O2 quotient was 0.24 +/- 0.21. Among the substrates measured, glucose appears to be the major metabolic fuel of the pregnant guinea pig uterus, but does not account for all of the oxygen consumed by the uterus if adjusted for lactate production, since lactate is produced within the gravid uterus in large quantities. Acetoacetate and beta-hydroxybutyrate are utilized in negligible amounts. PMID- 4034287 TI - Relation of age, race, and allotype to immunoglobulin subclass concentrations. AB - Concentrations of IgG1, IgG2, and total IgG were measured by a solid phase radioimmunoassay in sera from 36 healthy adults and 114 healthy children. As expected, IgG2 and total IgG had a positive correlation with age in children. In addition to age, several other factors were associated with significant differences in serum subclass concentrations. Female children had higher concentrations of IgG1 than males, and black subjects had significantly higher concentrations of IgG1, IgG2, and total IgG than whites. Although Km(1) and Gm(23) immunoglobulin allotypes had no relation to subclass concentrations when tested as single factors, the Km(1) allotype interacted significantly with race so that Km(1)-positive black children had higher IgG2 concentrations than other subjects. Our findings may explain, in part, recent observations of an association of the Km(1) allotype with altered immune responses of blacks to certain vaccines containing bacterial polysaccharides. In addition, our data indicate the need to control factors such as sex, race, and allotype in studies of subclass concentrations or immune responses. PMID- 4034288 TI - Role of dietary protein adaptation at weaning in the development of the rat gastrointestinal tract. AB - To evaluate the role of the quantitative adaptation in dietary protein at weaning in the growth and maturation of the rat gastrointestinal tract, we studied parameters of tissue mass, DNA synthesis, and enzyme activities in suckling pups weaned by day 17 to a semipurified synthetic, isocaloric diet that contained either 8 or 27% casein (controls). Rats of both groups were studied on days 21, 28, and 35 postpartum. On day 21, protein restriction had little effect on mean body weight, wet stomach and liver weight, gut length and colonic, jejunal or ileal mucosal weights per centimeter, whereas on day 35, all these tissue mass parameters were significantly (p less than 0.01 versus controls) depressed in the 8% protein group. DNA and protein content expressed per intestinal segment or per total organ and the protein/DNA ratio paralleled the changes in tissue mass, except that total DNA of the small intestine was decreased by 33% (p less than 0.01 versus controls) in 21-day-old rats with protein restriction. In the same age group, DNA synthesis rate, measured by the incorporation rate of [3H] thymidine per milligram tissue DNA, was markedly depressed in the small intestine (4-fold decrease; p less than 0.001 versus controls) and in the liver (2-fold decrease; p less than 0.05 versus controls) while in the colon the effect of protein restriction occurred later (day 35).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4034289 TI - Differential toxicity of RCAII (ricin) on rabbit intestinal epithelium in relation to postnatal maturation. AB - The purpose of this work was to assess the toxic lectin ricin (RCAII) as a probe for the study of intestinal permeability in the developing small bowel. Jejunal explants from suckling and adult rabbits were exposed to varying dosages of RCAII for 30 min at 25 degrees C and then cultured in toxin-free medium. The RCAII dose required to inhibit protein synthesis during 6 h of culture increased from 0.1 microgram/ml in 4-day-old rabbits to 25 micrograms/ml in weanling rabbits. RCAII cytotoxicity was almost completely blocked by 0.1 M lactulose in all age groups. The kinetics of 125I-RCAII binding to purified microvillus membranes were determined by incubating a fixed concentration of membrane protein (30 micrograms) with increasing concentrations of labeled lectin (2-18 micrograms/ml). Binding attained saturation with adult but not with suckling animal membranes. The latter yielded a curvilinear relationship in Scatchard plots, suggesting either several classes of binding sites or negative cooperativity. RCAII binding was confined to the delipidated fraction of the membranes and decreased by 42% from 6 days old to adult age. The extreme sensitivity of colostral epithelium to RCAII is probably related to the high level of endocytosis exhibited by the immature membrane of suckling rabbits. The development of increasing resistance to the toxin, and associated decrease in binding, might be related to disappearance of saccharide sites in productive surface receptors occurring in the developmental course of intestinal glycosylation. PMID- 4034290 TI - The analysis of human sweat proteins by isoelectric focusing. I. Sweat collection utilizing the macroduct system demonstrates the presence of previously unrecognized sex-related proteins. AB - The presence of high concentrations of sodium in the sweat of patients with cystic fibrosis is widely accepted by all investigators as one of the most important manifestations of the genetic defect. However, the simple means of sweat collection utilized for diagnostic purposes has been extended to the biochemical and physical analysis of the macromolecular components of human sweat. The most popular technique for the attainment of sweat has been collection of sweat droplets from the skin surface following heat stimulation. In this report, it is demonstrated that a far superior means of sweat collection exists based on a new collection device called the MACRODUCT. Utilizing this device, in conjunction with thin-layer isoelectric focusing, demonstrated that human sweat contains sex-specific proteins expressed in adult males and absent or greatly decreased from females and prepubertal males. Additionally, results are presented which suggest that the presence of epidermal keratins are an excellent marker for sweat contaminated with nonsweat gland-derived macromolecules. PMID- 4034291 TI - [Participation of a physician in the cooperation between a sick child and his family during treatment of neoplastic blood disease]. PMID- 4034292 TI - [Acute autoimmune hemolytic anemia with warm antibodies in an infant]. PMID- 4034293 TI - [Chromosome aberrations in Fanconi's aplastic anemia]. PMID- 4034294 TI - Episodes of apnea and bradycardia in the preterm newborn: impact on cerebral circulation. AB - The effect of episodes of apnea with bradycardia on cerebral circulation was studied during 101 episodes in 15 premature infants. The objectives of the study were to determine whether important alterations occur in cerebral hemodynamics with apnea and bradycardia and whether such alterations relate to systemic hemodynamic events. The transcutaneous Doppler technique was used to measure blood flow velocity in the anterior cerebral arteries. With episodes of apnea complicated by mild-to-moderate bradycardia (heart rate less than 120 or greater than 80), a decrease in diastolic flow velocity was noted with little or no change in systolic flow velocity. With episodes complicated by severe bradycardia (heart rate less than 80), the diastolic flow velocity fell to the electronic base line, and a progressive decrease in systolic flow velocity also was observed. Accompanying the changes in cerebral blood flow velocity were similar changes in arterial blood pressure. These data suggest potential deleterious hypoxic-ischemic effects on brain from apnea with severe bradycardia in the preterm infant. PMID- 4034295 TI - Relationship of serum bilirubin levels to ototoxicity and deafness in high-risk low-birth-weight infants. AB - During a 4-year period, 12 premature infants, all less than 34 weeks of gestation and all with a bilirubin level above 240 mumol/L (14 mg/dL) were determined to have bilateral sensorineural deafness. In order to to investigate how far the hyperbilirubinemia or any a associated factor might have been a causative factor, all infants of 34 weeks of gestation or less who had a serum bilirubin level above 240 mumol/L were investigated. For a period of 4 years, 99 infants meeting these criteria were classified as high risk or low risk on the basis of perinatal risk factors. Eight of the 22 high-risk infants with birth weight less than 1,500 g, but only two of 43 high-risk infants with birth weight greater than 1,500 g were deaf (P less than .05). The deaf infants were also matched with infants of normal hearing who had similar bilirubin levels and the same number of adverse perinatal factors. The mean duration of hyperbilirubinemia was significantly longer in the deaf infants (P less than .02), and they appeared to have a greater number of acidotic episodes while they were hyperbilirubinemic. These findings suggest that in healthy preterm infants with birth weight greater than 1,500 g, high bilirubin levels carry little risk, whereas a serum bilirubin level greater than 240 mumol/L in high-risk preterm infants with birth weight of 1,500 g or less is associated with a high risk of deafness. PMID- 4034296 TI - Subcutaneous versus intramuscular growth hormone therapy: growth and acute somatomedin response. AB - To determine the optimal route of growth hormone administration, a comparison was made of the acute somatomedin response and chronic growth response to either intramuscular or subcutaneous growth hormone in 20 children with growth hormone deficiency. None of the children had received growth hormone for at least 2 weeks prior to their random selection to receive growth hormone by either the subcutaneous (N = 11) or intramuscular (N = 9) route. Plasma samples for determination of levels of insulin-like growth factors I and II (IGF-I and IGF II) were obtained prior to therapy and 20 hours after the first and fourth of four daily injections of growth hormone. Growth rate and growth hormone antibody levels were determined before and after 6 months of therapy. IGF-I levels tripled in both treatment groups after four days of growth hormone injections, whereas IGF-II levels nearly doubled, with no significant difference between the intramuscular or subcutaneous group. After 6 months of therapy, there was no significant difference in growth rate and only two patients had developed growth hormone antibodies. Both patients and parents expressed a preference for the subcutaneous method. The identical rises in the IGF-I and IGF-II levels following a brief course of either subcutaneous or intramuscular injections of growth hormone, the similar growth rates, the low incidence of antibody development, and the preference for the subcutaneous route all suggest that the subcutaneous route is the method of choice for chronic growth hormone therapy. PMID- 4034297 TI - Subsequent pregnancy in mothers of infants with congenital heart disease. AB - Pregnancy rates for mothers of infants with conotruncal cardiac malformations and mothers of healthy control infants were compared for a 3-year period. Mothers of infants who died of congenital heart disease had the highest pregnancy rates, followed by control mothers, and then by mothers of surviving infants with congenital heart disease. Comparison in relation to the number of living children showed similar subsequent pregnancy rates for mothers of deceased infants with congenital heart disease and mothers of control infants, but lower rates for mothers of surviving infants with congenital heart disease. "Replacement" of a deceased infant occurs frequently, apparently in order to achieve a desired family size, whereas decreased reproduction in families of living infants with congenital heart disease may reflect the psychosocial and economic impact of the continuing care of a child with severe heart disease. PMID- 4034298 TI - Demographic analysis of childhood pedestrian injuries. AB - Factors in a child's living environment and socioeconomic background that contribute to the risk of pedestrian injury were studied. In 1982, in the city of Memphis, there were 210 pedestrian injuries among children aged 0 to 14 years, a rate of 138/100,000 children. The injured child was most often male, with mean age of 7.3 years; the child was usually struck while crossing the street between intersections, most commonly during the hours from 2 to 7 PM. Pedestrian injuries occurred in 81 of the 142 census tracts in the city. Compared with census tracts without reported injuries, these tracts had twice the percentage of nonwhite population, lower household incomes, more children living in female-headed households, more families living below the poverty level, and greater household crowding (all differences significant at P less than .01). The single variable of crowded housing per acre best predicted the number of injuries per acre in multiple regression analysis. A group of children who are at high risk of pedestrian injury through increased exposure in the environment was identified. As with many other types of injuries, modification of external factors--in this case, traffic engineering modifications--seems to be the most practical solution. PMID- 4034299 TI - Motor vehicle accident trauma and restraint usage patterns in children less than 4 years of age. AB - In a sample of children less than 4 years of age, treated in an emergency room after a motor vehicle accident, 22% were restrained in a child safety seat (improper and proper), 12% were restrained by a vehicle seat belt, and 70% were unrestrained. Trauma and injury patterns related to the various restraint use patterns are described. Most children in safety seats and seat-belted children, if injured, sustained minor contusions, abrasions, or lacerations. Injury among properly restrained children in safety seats was primarily the result of unavoidable mechanisms (eg, flying glass, intrusion). Improper use contributed to injury among safety-seat-restrained children, primarily by allowing the child to hit against the vehicle interior. Seat-belted children also were injured, primarily by hitting against the vehicle interior. Although some of the restrained children were seriously injured, in general, restrained children tended to sustain less serious and fewer injuries than the unrestrained children. PMID- 4034300 TI - Increased risk of gastrointestinal perforations in neonates mechanically ventilated with either face mask or nasal prongs. AB - Twenty cases of gastrointestinal perforations not associated with necrotizing enterocolitis or a bowel obstruction (GPNN) were reviewed. Fifteen infants suffered perforations during cycle ventilation. Perforations were localized in the stomach, duodenum, ileum, and jejunum. To determine if the type of mechanical ventilation used (ie, face mask, nasal prongs, or endotracheal tube) was associated with GPNN, a matched case-control analysis was performed. Case and control infants were matched by means of Apgar scores, gestational age, and length of time on ventilatory support. The Mantel-Haenszel estimate for estimating odds-ratios was used to determine that infants ventilated with nasal prongs or face mask were more likely to develop a gastrointestinal perforation than control infants ventilated with endotracheal tubes (odds-ratio greater than or equal to 29.6). This risk was associated with both upper gastrointestinal perforations (odds-ratio greater than or equal to 21.0) and lower gastrointestinal perforations (odds-ratio greater than or equal to 15.3). Routine use of mechanical ventilation with either nasal prongs or face mask appears to be associated with an unacceptable risk of gastrointestinal perforations in sick neonates. PMID- 4034302 TI - Teaching car passenger safety to preschool children. AB - An educational curriculum entitled "Bucklebear" was designed to increase safety seat and seat belt use in young children enrolled in preschool programs (day care centers and nursery schools). Three basic concepts were emphasized: (1) "buckling up" is a good habit for everyone for every ride; (2) the back seat is the best seat; and (3) there are desirable passenger behaviors. The curriculum included training workshops with teachers, parent meetings, classroom lessons, sound filmstrip, puppet play, and many other activities. Six experimental programs and seven control programs with 402 and 427 enrolled children, respectively, participated. After their participation in the educational curriculum, children in the experimental program increased their use of a safety seat or seat belt from 21.9% to 44.3%. These children also increased their knowledge and simulated practice of car passenger safety. PMID- 4034301 TI - Atypical bacterial infections explained by a concomitant virus infection. AB - Because both viral and bacterial infections are common during early childhood, dual infections are not unexpected. However, the clinical manifestation of such combined infections may be, difficult to interpret, and they are often misdiagnosed as "atypical bacterial infection." Five patients with concomitant viral-bacterial infections are described. In all five cases, virus detection enabled the physicians to better understand an otherwise puzzling clinical presentation. In view of the recent progress in rapid viral diagnoses and the potential of antiviral drugs, the possibility of dual infection should be investigated more often. PMID- 4034303 TI - Congenital posterior choanal atresia. AB - Although described more than two centuries ago, congenital choanal atresia remains an entity for which optimum treatment is not yet established. In a study of 29 cases of cogenital choanal atresia during a 14-year period, 14 male and 15 female patients were diagnosed, in contrast with the 2:1 female-male ratio usually reported. Thirty-two operative procedures were performed on 16 surgically treated patients in the series. The two classes of surgical treatment, transpalatal and transnasal techniques, were marked by 66% and 73% recurrence rates, respectively, from 2 months to 6.5 years of follow-up. In previous studies, facial growth disturbances have been shown to result from transpalatal resection in the growing child, whereas transnasal techniques have been indicted as a cause of serious neurologic complications. Because no major morbidity resulted from 20 endonasal procedures in this series, early serial endonasal perforation is advocated as a means of establishing and maintaining a patent nasal airway until definitive transnasal repair can be performed when facial growth is more complete. PMID- 4034304 TI - Personnel in neonatal pediatrics: assessment of numbers and distribution. AB - There has not been an accurate assessment made of the number of practicing neonatologists, attrition rate of neonatologists, or geographic distribution of neonatologists; therefore, a telephone survey was conducted to assess these issues. The basic conclusion of this study is that numbers and distribution of neonatologists, as well as ratio to patient population, are not deficient or disproportionate when analyzed on a nationwide basis. PMID- 4034305 TI - National Institutes of Health report on causes of mental retardation and cerebral palsy. Task Force on Joint Assessment of Prenatal and Perinatal Factors Associated with Brain Disorders. PMID- 4034306 TI - Will there be a tomorrow without the children? PMID- 4034307 TI - Fifth versus fourth Korotkoff phase. PMID- 4034308 TI - American Academy of Pediatrics Committee on Pediatric Manpower: Pediatric manpower recommendations. PMID- 4034309 TI - American Academy of Pediatrics Committee on Hospital Care: Child life programs for hospitalized children. PMID- 4034310 TI - Hunger debate. PMID- 4034311 TI - Neonatologist versus general pediatrician. PMID- 4034312 TI - Pesticide residues in food. PMID- 4034313 TI - [Nonspecific protection factors in the pathogenesis of chronic gastroduodenitis in children]. PMID- 4034314 TI - [Biogenic amines in gastroduodenal pathology in children]. PMID- 4034315 TI - [Morphometry of the gastric and duodenal mucosa in the diagnosis of chronic gastroduodenitis in children]. PMID- 4034316 TI - [Intrajejunal bactericidal activity and jejunal microbial colonization in children with chronic gastroduodenitis]. PMID- 4034317 TI - [Neurophysiological mechanisms, serotonin metabolism and dysbacteriosis in the pathogenesis of chronic colitis in children]. PMID- 4034318 TI - [Clinical importance of determining lysozyme in secretions and blood serum in chronic liver diseases in children]. PMID- 4034319 TI - [Assessment of the degree of activity of chronic hepatitis in children by morphometry of liver biopsies]. PMID- 4034320 TI - [Current problems of pediatric gastroenterology]. PMID- 4034321 TI - [Endoscopic retrograde pancreatocholangiography in children]. PMID- 4034322 TI - [Simultaneous microscopic and bacterioscopic examination of children's urine in the polyclinic]. PMID- 4034323 TI - [Clinical characteristics of duodenal ulcer complications in children and the procedure for their treatment]. PMID- 4034324 TI - [Diagnosis of the chronic diarrhea syndrome in young infants and preschoolers]. PMID- 4034326 TI - [Diet therapy of celiac disease in children]. PMID- 4034325 TI - [Clinical aspects and treatment of functional fecal incontinence in children]. PMID- 4034327 TI - [Means of improving medical care for children with foreign bodies in the respiratory tract]. PMID- 4034328 TI - [Use of hemosorption in the resuscitation department of a pediatric infectious disease clinic]. PMID- 4034329 TI - [Experience with the use of anatomical reference points in catheterizing the subclavian veins of children]. PMID- 4034330 TI - [Differential diagnosis of nonspecific ulcerative colitis in children]. PMID- 4034331 TI - [Dyslipidemias in children]. PMID- 4034332 TI - [2 cases of duodenal peptic ulcer in preschool children]. PMID- 4034333 TI - [Immunoglobulins in the digestive secretions of healthy children]. PMID- 4034334 TI - [Functional evaluation of the complement system in children with digestive organ pathology]. PMID- 4034335 TI - Quantitative changes in steroid and peptide hormones in the maternal fetoplacental system between the 28th-40th weeks of pregnancy. AB - The role of steroid and peptide hormones in the maintenance of pregnancy and in the onset of labour was investigated in the maternal-fetoplacental system between the 28th-40th weeks of pregnancy. The data of 151 pregnant women and 108 newborns was processed, and a total of 2385 samples was studied by RIA. Results showed that between the 28th-40th week there is an increase in the prolactin level of the umbilical arterial and venous blood with a parallel increase in the cortisol level of umbilical arterial blood and a fall in the progesterone level of umbilical arterial and venous blood which between the 36th and 40th week results in a rise of the oestradiol/progesterone quotient. At the same time the oestradiol concentration rises in the maternal circulation and in case of premature labour the oestradiol/progesterone quotient attains values twice as high as those found in normal pregnancies. The alteration of the hormonal environment expedites the predominance of the mechanisms stimulating the activity of the myometrium. The hormone values in the umbilical artery and vein characteristically differ from those of the maternal serum. Thus, it may be assumed that the fetus, though being in close communication with the maternal organism, is capable of independently maintaining its hormonal environment. The results indicate that the fetus or more accurately the fetoplacental unit plays a significant part in the maintenance of pregnancy and in the initiation of labour than it has been assumed previously. PMID- 4034336 TI - Comparative study of intravenous anaesthetic techniques administered during short term gynecological operations. AB - The effects of nine intravenous anaesthetic techniques on serum cortisol level and circulatory parameters were studied in healthy patients undergoing termination of pregnancy. Considering the increased pre-operation values and those of the pregnant control group as well as diurnal variations, it was found that the serum cortisol value changed during and after the procedure depending on the type of anaesthesia used. This might mean that the optimal type of anaesthesia for interruption could be designed by measuring the serum cortisol level, assuming that this parameter was one of the indicators of stress. The rating the different types of anaesthetics, the circulatory parameters were also considered. According to these criteria the best results were observed using methohexital in combination with fentanyl or diazepam. PMID- 4034337 TI - The effect of sera of patients with systemic lupus erythematosus on artificial immune complexes. AB - The solubilization of artificial immune complexes mediated by complements has been well-known since 1975. It is known that the process is bound to the integrity of the alternative complement pathway. The phenomenon of solubilization can be used in the investigation of the function of the complement system. We have studied the solubilization of artificial complexes containing BSA and 125I labelled anti-BSA on the effect of sera of healthy subjects and those of patients suffering from SLE. We have observed that the solubilization capacity of SLE sera is significantly lower than that of healthy persons. The decrease is the most distinct at the time of the activity of the disease. PMID- 4034338 TI - Serum IgE level in systemic lupus erythematosus. AB - The serum total-IgE level has been studied in systemic lupus erythematosus (SLE), in order to obtain data concerning the significance of IgE antibodies in the appearance of SLE symptoms. In most patients the serum IgE content was significantly higher in the active stage of the disease than during remission. The findings indicated a specific statistical distribution due to the multiple factors influencing IgE production and so an augmented IgE level cannot be regarded as a reliable feature of SLE activation. PMID- 4034339 TI - The clinical value of the His-bundle electrogram in intraventricular conduction defects. AB - A study concerned with the clinical significance of the His-bundle ECG was carried out in association with upper atrial stimulation in 20 patients with intraventricular conduction defect. On the ground of the results the His-bundle ECG is regarded as a procedure of diagnostic value in intraventricular conduction defects by contributing to the accuracy of information on the severity and extent of the lesion. In the framework of published observations, including the present findings, questions relating to prognosis and to the necessity for pacing in bifascicular block are discussed. PMID- 4034340 TI - Production and properties of antiserum for radioimmunoassay of serum conjugated chenodeoxycholic acid and its preliminary application. AB - Sensitive tritiated radioimmunoassay was developed for conjugated chenodeoxycholic acid, using immunogen prepared by the mixed anhydride method. The obtained molar bile salt-BSA ratio in the immunogen was 19:1. The distinguishing features of the immunization procedure were a preliminary vaccination of the animal with antitubercular vaccine (VDS), and the administration of very small doses of immunogen (50 micrograms). Assay sensitivity for this bile salt fell in the picomole range with the standard curve extending from 1.5 to 150 pmol. Specificity of the antiserum was compared with that of the commercially available "Glycochenodeoxycholic acid RIA kit" (Nordiclab Oy, Oulu, Finland), and proved to be satisfactory. Fasting serum conjugated chenodeoxycholic acid concentration in 25 healthy subjects and 15 patients with cirrhosis was 0.63 mumol/l and 43.05 mumol/l, respectively. The assay was performed on unextracted sera. PMID- 4034341 TI - [Acquired immunodeficiency syndrome in older children]. AB - The authors report 3 cases of AIDS in children 10 and 11 years of age. These cases fulfill the definition of AIDS such as established by C.D.C. (Centers for Disease Control, Atlanta, Georgia U.S.A.) As opportunistic infections, the first case had oral moniliasis, the second case presented with ganglionic form of Kaposi Sarcoma and the third case had cryptococcal meningitis. The mode of transmission in this age group is unknown. Only one child had repeated transfusion. The parents of these children are in good health and were not at risk for AIDS. PMID- 4034342 TI - [The Vater association in a newborn infant of a diabetic mother]. AB - Concerning the case history of an infant of diabetic mother, the authors analyse the possible relationship between a VATER association and a poorly controlled diabetes mellitus in the early weeks of pregnancy. Caudal regression syndrome, the most frequently observed malformation noted in infants of diabetic mothers and VATER association are the results of an "AXIAL MESODERMAL DYSPLASIA". Furthermore, the factors causing VATER association occur before the seventh week of pregnancy like those responsible for the anomalies observed in infants of diabetic mothers. It is possible that a poorly controlled diabetes mellitus before conception and in the early weeks of pregnancy could favour the appearance of VATER association. PMID- 4034343 TI - [Salmonella panama responsible for meningitis secondary to febrile gastroenteritis in a 3-month-old infant]. AB - The authors report a case of meningitis following enteritis due to Salmonella Panama (group D). The severity of Salmonella infection is especially correlated with hematogenous dissemination, through a transitory lack of intestinal immunity. The limited efficacy of antibiotics in salmonellosis is responsible for an ambiguous preventive attitude towards salmonella meningitis. PMID- 4034344 TI - Scale, key, and contour in the discrimination of tuned and mistuned approximations to melody. PMID- 4034345 TI - Statistical properties of forced-choice psychometric functions: implications of probit analysis. PMID- 4034346 TI - Identifying objects by touch: an "expert system". PMID- 4034347 TI - Absence of relational determination in the rod-and-frame effect. PMID- 4034348 TI - Identification and discrimination of consonant-vowel syllables by younger and older adults. PMID- 4034349 TI - Lateral inhibition between spatially adjacent spatial-frequency channels? PMID- 4034350 TI - On size, distance, and visual angle perception. PMID- 4034351 TI - The dissociation of position and extent in Muller-Lyer figures. PMID- 4034352 TI - Acquisition and decision during target search of visual letter displays. PMID- 4034353 TI - Categorization and normalization of vowels by 3-year-old children. PMID- 4034354 TI - Binocular interaction in induced line rotation. PMID- 4034355 TI - Identification and discrimination of sweep tones. PMID- 4034356 TI - Does testing initiate decay of McCollough effects? PMID- 4034357 TI - Imagery effects on early visual processing. PMID- 4034358 TI - Letters are visual stimuli: a comment on the use of confusion matrices. PMID- 4034359 TI - Reflections on enjoyment. PMID- 4034360 TI - Evolution of the human mind and emergence of tribal culture: a mentalist approach. PMID- 4034361 TI - Gender chauvinism and the division of labor in humans. PMID- 4034362 TI - Biological and social evolution: another view. PMID- 4034363 TI - Quality of life: an ideological critique. PMID- 4034364 TI - Art for psych's sake. PMID- 4034365 TI - Fatness, menarche, and female fertility. PMID- 4034366 TI - Skin AVA and capillary dilatation and constriction induced by local skin heating. AB - In conscious sheep, total femoral blood flow and flow through arteriovenous anastomoses (AVAs) and capillaries (CAP) in skin of the hindleg were measured employing electromagnetic and radioactive microsphere techniques. Core temperature (Tc) was manipulated using intravascular heat exchangers and hindleg skin temperature (Tsk) was manipulated by immersion in temperature controlled water. With Tc set 1 degree C above normal, AVA flow was highest at the lowest Tsk tested (34 degrees C); AVAs progressively constricted as Tsk was increased from 34 to 40-41 degrees C, then dilated again as Tsk reached the highest levels tested (42-44 degrees C). Skin CAP flow was not altered by Tsk of 34 to 42 degrees C but was increased at a Tsk of 44 degrees C. Therefore total skin blood flow followed essentially the same pattern as AVA flow; total femoral flow also followed this pattern. When Tc was set 0.5 degrees C below normal, AVA flow was low at all levels of Tsk. It is concluded that Tc plays a dominant role in control of skin blood flow, however, once Tc is at a level requiring increased heat loss, Tsk exerts an extremely potent influence on the nature and magnitude of changes in skin blood flow. The pattern of flow changes appears to reflect principally a negative feedback mechanism aimed at maintaining Tsk at approximately 40 degrees C; this may contrast with mechanisms associated with sweating and/or active vasodilatation in other species. PMID- 4034367 TI - Effect of adenosine and its stabile analogue 2-chloroadenosine on cerebrocortical microcirculation and NAD/NADH redox state. AB - In the present study, the effects of topically applied adenosine (ADO) and its stabile analogue 2-chloroadenosine (CADO) on cerebrocortical microcirculation and NAD/NADH redox state (oxidized/reduced nicotinamide adenine dinucleotide) were investigated. Vascular volume (CVV), mean transit time of blood flow (tm), blood flow (CBF), and NADH fluorescence of the cat brain cortex were measured through a cranial window with a microscope fluororeflectometer. The reference values of CVV, tm, and CBF, measured in the artificial cerebrospinal fluid (mock CSF) which superfused brain cortex, were regarded as 100%. Adenosine and 2-chloroadenosine, in the concentration range of 10(-6) - 10(-3) M, resulted in concentration dependent increases in CBF and NAD reduction. 10(-5) M adenosine and 2 chloroadenosine increased CBF by 49.6 +/- 5.6% and 80.4 +/- 10.3%, respectively. At a pharmacologically high concentration (10(-3) M), ADO increased CBF by 164.6 +/- 13.5%, CADO by 333 +/- 44%. At the same time, 10(-3) M ADO and CADO shifted the cortical NAD/NADH redox state by 7.9 +/- 0.4% and 12.4 +/- 0.7%, respectively toward a more reduced state. Our results, concerning the vasodilator potency of adenosine and 2-chloroadenosine, accord with available data in the literature. However, the pronounced NAD reduction obtained with these adenosine nucleosides suggests that, besides an action on vascular adenosine receptors, some other changes, such as increased substrate mobilization and possibly cAMP production, may contribute to the vasodilator effect of adenosine and 2-chloroadenosine. PMID- 4034368 TI - Regional differences in the electrical activity of the rabbit sinus node. AB - In order to study regional differences in membrane properties within the sinus node, we have investigated the electrical activity of small specimens of tissue (approximately 0.3 mm in diameter) that have been prepared from the central, transitional and peripheral areas of the rabbit sinus node. The action potential upstroke velocity and overshoot as well as the maximum diastolic potential were significantly greater in tissue from the peripheral area. Paradoxically, the rate of spontaneous activity was slowest in tissue from the central area (normally the leading pacemaker site in the intact heart). Recovery of excitability was slowest in tissue from the central area and fastest in tissue from the peripheral area. The depression of electrical activity produced by rapid stimulation (overdrive) was most marked in the central region. Raising the bathing K concentration depresses spontaneous activity and this effect was again most marked in the central region. Tissue from the central area was the least sensitive to acetylcholine in five out of six hearts. Pacemaker shift can occur within the sinus node in response to various interventions, and differences in electrical activity as observed in this study may underlie such changes. PMID- 4034369 TI - Mechanism of rapid phosphate (Pi) transport adaptation to a single low Pi meal in rat renal brush border membrane. AB - Previous studies have shown that the adaptive response of tubular inorganic phosphate (Pi) transport to Pi deprivation is detectable in the whole kidney 24 h after switching rats from a high (HPD) to a low (LPD) Pi diet. In the present work we report on a more rapid adaptive response of the sodium (Na)-dependent Pi transport system located in the luminal membrane of the proximal tubule and its relation with changes in phosphatemia an parathyroid hormone status. Rats were fed HPD and trained to eat their daily ration within 1 h. After two weeks of equilibration half of the animals received a single LPD ration. 1, 2 and 4 h after the end of food consumption the animals were either sacrificed for renal cortical brush border membrane vesicle (BBMV) isolation or used for determining plasma Pi concentration, urinary excretion of Pi and cAMP. The results indicate that 2 and 4 h after the end of feeding, the Na-dependent Pi transport in BBMV was stimulated by 70 and 140% respectively in intact rats exposed for the first time to LPD. This response was preceded by a significant fall in plasma Pi concentration (HPD: 2.46 +/- 0.03, LPD: 2.04 +/- 0.05 mM), in the urinary excretion of Pi (HPD: 899.0 +/- 68.1; LPD: 6.5 +/- 3.3 mumol/ml GFR) and cAMP (HPD: 76.9 +/- 7.4, LPD: 48.2 +/- 1.4 pmol/ml GF). This last result suggested a rapid inhibition of PTH after one single LPD feeding.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4034370 TI - Uphill transport of pyrimidine nucleosides in renal brush border vesicles. AB - The uptake of cytidine, of thymidine and of uridine in brush border vesicles prepared from the cortex of rat kidney has been studied by the technique of rapid filtration. The nucleosides were not metabolized in the vesicles. The time courses of uptake in the presence of inwardly directed gradients of Na+ and of K+ showed an overshoot, indicating uphill transport. The overshoot was much more pronounced with Na+ than with K+; it was not observed when Na+ was at equilibrium across the membrane. The uptake of the nucleosides was stimulated by an inside negative potential in the presence of Na+. These results provide evidence for a cotransport of pyrimidine nucleosides with Na+. The apparent Km's for the uptake of cytidine, of thymidine and of uridine were 3.76 mumol X 1(-1), 4.18 mumol X 1( 1) and 7.21 mumol X 1(-1) respectively. The uptake of the pyrimidine nucleosides was insensitive to 6-nitrobenzylthioinosine. This insensitivity as well as the high affinity for the nucleosides and the capacity for uphill transport indicate that the nucleoside carrier(s) is renal brush border is (are) different from the carriers found in most other cell types. PMID- 4034371 TI - Calcium-dependent action potentials in guinea-pig olfactory cortex neurones. AB - Ca2+-dependent action potentials were recorded in guinea pig olfactory neurones in vitro (23 degrees--25 degrees C). In most cells (in the presence of tetrodotoxin: TTX) the current-voltage relationship displayed 'anomalous' rectification (apparent high slope resistance) at potentials approximately 20 mV depolarized to the resting membrane potential (approximately -80 mV) and strong outward rectification at more positive potentials. Intracellular Cs+-loading blocked outward rectification and increased action potential duration. Such spikes were TTX-insensitive and were further prolonged by external addition of tetraethylammonium (TEA) or Ba2+. Spikes recorded from Cs+-loaded, TTX/TEA treated neurones displayed a prolonged plateau and an after-depolarization. They persisted when Ba2+ or Sr2+ were substituted for external Ca2+, but not when Mg2+ was the sole extracellular divalent cation. The spikes were blocked in the presence of Cd2+ but persisted when 82% of the extracellular Na+ was substituted by choline. A TTX-insensitive, slowly inactivating inward current at depolarized potentials is believed to account for the subthreshold 'anomalous' rectification and prolonged spike plateau. PMID- 4034372 TI - The extrarenal effects of aldosterone on the distribution of extracellular fluid in conscious adrenalectomized-nephrectomized rats. AB - In order to examine the extrarenal roles of aldosterone in cardiovascular homeostasis, the present study compared blood pressure, extracellular fluid volume (ECFV) and plasma volume (PV) in the three following groups: 10 nephrectomized (NX) rats, 10 nephrectomized-adrenalectomized (NX-AX) rats, and 10 NX-AX and aldosterone-treated (NX-AX-A) rats. Two-hundred and fifty micrograms of aldosterone, mixed with sesame oil, was given subcutaneously in the NX-AX-A rats. Mean arterial pressure (MAP) was recorded through previously implanted carotid catheters. ECFV and PV were measured using 35S-Na2SO4 and 131I-RISA, respectively, 24 h after the operation. These measurements were performed in an unanesthetized and unrestricted condition. MAP gradually increased in the NX group, while a gradual decrease was observed in the other groups. However, MAP was significantly higher in the NX-AX-A group than in the NX-AX group 6 h after the operation and thereafter. Changes in body weight were comparable in the three groups 24 h after the operation. ECFV and PV were both reduced in the NX-AX and the NX-AX-A groups as compared to the NX group (P less than 0.001 NX-AX vs NX, and P less than 0.05 and P less than 0.025 NX-AX-A vs NX, respectively). Although ECFV was comparable in the NX-AX and the NX-AX-A groups, PV was significantly greater in the NX-AX-A group than in the NX-AX group (P less than 0.05). There was a significant positive correlation between MAP and PV in the rats as a whole (r = 0.68, P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4034373 TI - Localization and properties of NAD+-dependent 15-hydroxyprostaglandin dehydrogenase activity in the rat kidney. AB - Localization of NAD+-dependent (type I) 15-hydroxyprostaglandin dehydrogenase (15PGDH) in the rat kidney was examined using an ultramicro assay of the enzyme activity based on the enzymatic cycling method. The enzyme activities during first 3 weeks of age were 30- to 40-fold higher than the adult and rapidly decreased by 4th week. 15PGDH activities measured with either PGE2 or PGF2 alpha as a substrate were five times higher in slices from midcortical or juxtamedullary layers than in slices from the superficial cortex of 3 week-old rat kidney. Little activity was found in inner medulla and papilla. When the enzyme activity was assayed using isolated nephron segments dissected from collagenase treated slices of 3 week-old rat kidneys, the activity was localized only in the proximal convoluted and straight tubules with either PGs (PGE2: 1.75 +/- 0.25 in PCT, 7.70 +/- 1.19 in PST, and PGF2 alpha: 1.63 +/- 0.39, 6.18 +/- 1.52 pmoles NADH/mm/40 min). The kinetic analysis for renal 15PGDH of 3 week-old rats revealed that Km for PGE2 (8.4 microM) was lower than that for PGF2 alpha (22.6 microM) with constant NAD+, while Vmax for both was similar. In contrast, both Km and Vmax for NAD+ were identical with either PGs. These data suggest that the rate-limiting factor of type I 15PGDH is the concentration of prostaglandins in the kidney rather than the concentration of NAD+.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4034374 TI - [Echocardiography and angiocardiography in overriding and straddling of mitral valve in Taussig-Bing anomaly. A case report]. PMID- 4034375 TI - [Computed tomography of the pericardium--normal and abnormal appearances]. PMID- 4034376 TI - [Evaluation of thyroid carcinoma with invasion of adjacent organs by CT]. PMID- 4034377 TI - [Imaging diagnosis of gas exchange in patients with lung cancer. Evaluation of regional ventilation and perfusion with functional imaging]. PMID- 4034379 TI - [ROC analysis of computed tomography and renal scintigraphy for renal diseases]. PMID- 4034378 TI - [Cavernous hemangioma of the liver. Diagnostic value of 99mTc in vivo labelled RBCs angiography]. PMID- 4034380 TI - [Analysis of lymphocyte subsets infiltrated into mouse tumor tissue exposed to local irradiation--histological study using monoclonal antibodies]. PMID- 4034381 TI - [Diagnosis and localization of pheochromocytoma]. PMID- 4034382 TI - [Methodology research. Bias I: Definitions and occurrence in controlled tests]. PMID- 4034383 TI - [WHO and Scandinavian health policy]. PMID- 4034384 TI - [New findings on osteoporosis]. PMID- 4034385 TI - [Diagnosis and treatment of instable dorsal and sacral spinal fractures]. PMID- 4034386 TI - The relationship between serum IgG levels and age, leg injuries, infections and weight gains in dairy calves. AB - Serum IgG profiles for calves up to 50 days varied markedly depending on the level of passively acquired immunity. A relationship between serum IgG at 5 days of age and prevalence of leg injuries (skin lesions) was found, whereas no associations were seen regarding IgG and diarrhoea or liveweight gain. PMID- 4034387 TI - An epidemiological study of factors affecting serum IgG levels in dairy calves. AB - Serum IgG was used to evaluate the immune status of calves up to 180 days of age in 300 Norwegian dairy herds. Several factors were found to significantly affect the levels. Among these were geographical district, season, and factors related to housing and feeding. PMID- 4034388 TI - Osteochondritis dissecans in the tibio-tarsal joint. Results by surgical treatment. AB - Osteochondrosis is a rapidly growing problem in the horse population and reports are frequent. Osteochondritis dissecans can in most cases be treated surgically, but reports on results are lacking. This paper reports the results of surgery of the tibiotarsal joint in 43 cases. PMID- 4034389 TI - Isospora suis species in a Danish SPF-herd. AB - In two studies carried out in 1974-75 on 10 eight and 25 two week old piglets obtained from a SPF-herd the endoparasitic status was determined. Samples of faeces were examined by microscopy which revealed the presence of Isospora suis, a finding that was quite unexpected in a SPF-herd. During days 17-23 pp. the 25 piglets were not found to excrete oocysts, the earliest findings of oocysts being made 24-35 days p.p. The 10 piglets being kept isolated in individual pens excreted oocysts up until 88 days p.p. The epidemiology of Isospora suis is discussed. PMID- 4034391 TI - [Tibial dyschondroplasia in broiler chickens]. AB - After the general description of tibial dyschondroplasia (TD) an account is given on observations of the incidence of this leg abnormality in the Danish broiler production. Comparative investigations concerning the frequency of TD in three commercial strains of broiler chickens (A, B & C) is described. The possible effect of the diet, with reference to frequency--particularly calcium and phosphorus levels--is studied. Chickens from each strain were divided into two equal groups; one was fed an ordinary broiler chicken diet (X), and the other was given feed (Y) originally composed for replacement pullets. The frequency of TD was 22 percent in broiler chickens from the commercial production. Irrespective of composition of the feed, almost the same incidence was recorded in both groups of one of the strains (A), while the frequency of TD in strains B & C was significantly lower on both diets. In relation to available observations and results, influence on incidence of genetic factors and certain feed ingredients is discussed. It is concluded that the TD-frequency is relatively high in the strain which dominates the Danish broiler production. This seems to be primarily determined by genetic factors, whereas in this experiment the levels of calcium, phosphorous and other feed ingredients have minor influence. PMID- 4034390 TI - Isolation of dermatophytes from domestic animals in Norway. AB - The examination of 2066 skin scrapings from domestic animals in the period from July 1981 to June 1984, revealed dermatophytes in 439 samples. Dermatophytes isolated were: M. canis in dog, cat, cattle, horse, swine, goat, rabbit and hamster, M. equinum in dog and horse, M. gypseum in horse, T. equinum in horse and cattle, T. mentagrophytes in dog, cat, cattle, horse, guinea pig and rabbit, T. verrucosum in cattle and E. floccosum in dog. PMID- 4034392 TI - Efficacy of vaccination against ringworm in cattle. PMID- 4034393 TI - Fate of exogenous recombinant plasmids introduced into mouse and human cells. AB - We have constructed a number of plasmids selectable in both E. coli and mouse or human cells. Human DNA sequences were inserted and the recombinant plasmids were used to transfect either mouse or human cells by the Ca-phosphate precipitation technique. We have observed that: (i) competent cells uptake large amounts of plasmid DNA; (ii) input plasmids persist in transformed mammalian cells as free unreplicating circular molecules for up to 20 generations; such persistence does not depend on the presence of selective markers; (iii) plasmids incorporated into mouse L-cells undergo widespread rearrangements (in the absence of replication) entailing mostly deletions of both human and bacterial sequences which yield smaller products; the latter appear to be more stable in a subsequent transformation cycle. Surprisingly such rearrangements are almost totally absent in transformed human KB-cells. This property of human KB-cells may prove useful for the development of a vector apt at cloning and expressing human DNA sequences. Unlike what has been observed in yeast, no "autonomously replicating sequence" can be detected in mammalian cells by randomly cloning human DNA sequences into a selectable plasmid and screening for an increased transformation efficiency. PMID- 4034394 TI - Nucleic acid binding drugs. Part XIII. Molecular motion in a drug-nucleic acid model system: thermal motion analysis of a proflavine-dinucleoside crystal structure. AB - The high-resolution crystal structure of the intercalation complex between proflavine and cytidylyl-3',5'-guanosine (CpG) has been studied by thermalmotion analysis. This has provided information on the translational and librational motions of individual groups in the complex. Many of these motions are similar to, though of larger magnitude than in uncomplexed dinucleosides. Pronounced librational effects were observed along the base pairs and in the plane of the drug chromophore. PMID- 4034395 TI - Evidence for sequence-specific conformational changes in DNA from the melting temperatures of DNA phosphorothioate derivatives. AB - Analogs of alternating purine-pyrimidine DNA polymers such as poly(dA-dT)-poly(dA dT) can be made with phosphorothioate groups in the DNA backbone. A phosphorothioate diester at the 5'-purine-pyrimidine-3' step causes a significant lowering of the polymer's melting temperature compared to a phosphorothioate diester at the 5'-pyrimidine-purine-3' step. This may occur because sulfur substitution increases anionic charge density in the DNA minor groove and 5' purine-pyrimidine-3' steps narrow the minor groove. The ability to modulate charge density in the DNA backbone via sulfur substitution should prove useful in studies of sequence-dependent conformational changes in DNA. PMID- 4034396 TI - Macronuclear DNA of Tetrahymena thermophila exists as defined subchromosomal sized molecules. AB - Using the method of orthogonal-field-alternation gel electrophoresis, we have resolved the macronuclear DNA of Tetrahymena thermophila into a series of distinct bands. Using electrode switching intervals ranging from 10 to 70 seconds we have resolved DNA bands ranging in size from about 21 kb up to and beyond the size of yeast chromosomes VII and XV. Hybridization of Southern blots from these gels to both unique and repetitive DNA sequences shows that the macronuclear genome of T. thermophila has a precise organization. The unique sequences tested each hybridize to only one band of macronuclear DNA and the hybridization patterns seem to be identical in several inbred strains examined. PMID- 4034397 TI - Melting transition of covalently closed DNA with supercoil-induced cruciforms. AB - The melting curve for covalently closed supercoiled DNA has been studied by assuming the existence of cruciforms as significant structural perturbations in the pre-melting region. The statistical mechanical treatment used incorporates these cruciform structures through an appropriate sequence generating function. The variation of the effective hydrogen bond energy with temperature is taken into account by an empirical procedure. The results obtained are in close agreement with the corresponding experimental data in TEA solution where the effect of heterogeneity of the base pairs is minimized. PMID- 4034398 TI - N-acetoxy-2-acetylaminofluorene modification of a deoxyoligonucleotide duplex. AB - The carcinogen N-acetoxy-2-acetylaminofluorene was reacted with d (CCACGCACC) to form a covalent adduct with attachment at the single guanine. The sample was purified, mixed 1:1 with d (GGTGCGTGG) and studied by thermal denaturation experiments. The Tm for the mixture was 35 +/- 3 degrees C, consistent with duplex formation. The method of continuous variation shows that the modified oligomer, d (CCACGAAFCACC), forms a 1:1 duplex with d (GGTGCGTGG). Circular dichroism spectra also indicate the formation of a duplex and suggest that the modified duplex has a left-handed conformation. Addition of the intercalating drug ethidium alters the CD spectrum of the modified duplex, resulting in a CD spectrum similar to that of ethidium bound to right-handed DNA. PMID- 4034400 TI - [Role of cellular oncogenes in the development of neoplasms]. PMID- 4034399 TI - UV irradiation of nucleic acids: formation, purification and solution conformational analysis of the '6-4 lesion' of dTpdT. AB - Irradiation of dTpdT with 300 kJ/m2 of 254 nm produces numerous photo-products, one of which labeled dT6pd4T[1] was purified by HPLC. dT6pd4T has a UV spectrum (H20, pH 7) with lambda max = 326 nm and lambda min = 265 nm, and a P-31 NMR resonance at -3.46 ppm (normal dTpdT occurs at -4.01 ppm; TMP, 30 degrees C). 2-D COSY NMR spectra facilitated proton resonance assignments and 2-D NOESY spectra aided analysis of spatial orientation. Carbon-13 and proton-coupled P-31 NMR spectra of dT6pd4T were also obtained. These analyses indicate: C5=C6 of dT6p- is saturated and the -pd4T base is more aromatic; the dT6p- base possesses a configuration of 5R, 6S; dT6p- and -pd4T have anti-type glycosidic conformations; furanose conformation of dT6p- is mainly C3'-endo and that of -pd4T exists in a C3'-endo in equilibrium C3'-exo; exocyclic bonds gamma (C5'-C4'), beta (05'-C5') and epsilon (C3'-03') are non-classical rotamers; dihedral angle about epsilon (C3'-03') is smaller relative to dTpdT. PMID- 4034401 TI - [Monoclonal antibodies--new methods of diagnosing and treating cancers of the digestive tract]. PMID- 4034402 TI - [The kinetics of neoplastic tumors. II. Principles of determining various indicators of the growth of neoplastic tumors in clinical studies]. PMID- 4034403 TI - [Significance of the number of fractions and total time of treatment in the radiotherapy of neoplasms in the light of current opinions and our studies]. PMID- 4034405 TI - [Ultrastructural changes in neoplastic cells of the bone marrow of a patient with multiple myeloma]. PMID- 4034404 TI - [Evaluation of the effect of selected individual and environmental factors on the risk of development of cervical cancer]. PMID- 4034406 TI - [Primary cancers of kidney pelvis and ureter]. PMID- 4034407 TI - Alternating monotherapy is the preferred treatment. AB - The choice of initial therapy of hypertensive patients may be critical in the long-term efforts to reduce premature cardiovascular morbidity and mortality. In the 1984 report of the third Joint National Committee (JNC), significant changes in the usual approach to initial therapy were suggested, including a more conservative approach toward the institution of drug therapy, more liberal use of nondrug therapies and broader choices for the initial drug. I support these changes and believe that even a greater number of choices for initial therapy should be considered. I am increasingly concerned about the hazards of diuretic therapy and believe that for most patients, an adrenergic inhibitor is preferable for first drug. Rather than limit the type of adrenergic inhibitor to a beta blocker as suggested in the JNC report, either an alpha blocker or a centrally acting drug may be preferable. In the near future, calcium antagonists will likely also become logical choices. PMID- 4034409 TI - Pro-enkephalin peptides possessing Met-enkephalin-Arg6-Gly7-Leu8-immunoreactivity in rat CSF, striatum and adrenal gland. AB - Cerebrospinal fluid (CSF) taken from rats implanted with chronic cisternal cannulae and extracts prepared from rat adrenal gland and striatum were subjected to Sephadex G-50 chromatography and HPLC. Fractions were monitored using specific radioimmunoassays (RIA) for the pentapeptide methionine enkephalin (Met-Enk) and methionine enkephalin-Arg6-Gly7-Leu8 (Met-EnkRGL). In rat CSF, striatum and adrenal gland, three Met-EnkRGL-immunoreactive (IR) peaks of Mrs 8000, 5000 and 1000 daltons were detected. The same peaks were also found to possess Met-Enk immunoreactivity after enzyme digestion of Sephadex G-50 fractions with trypsin and carboxypeptidase B (CPB), suggesting their derivation from proenkephalin. HPLC of the 8K and 5K peaks on a column of Ultrapore RPSC showed them to elute discretely with similar retention times, indicative of hydrophobic peptides of large molecular weight. Their similar hydrophobicities yet significant separation during gel filtration would suggest that the 8K and 5K peptides are structurally closely related yet different with respect to their molecular weights. HPLC of the small molecular weight material from rat striatum and adrenal gland revealed the presence of Met-EnkRGL and Met-EnkRGL sulphoxide in both tissues. In rat striatum Met-Enk and its sulphoxide were also detected. The oxidised pentapeptide was found to be present in rat CSF, together with two unidentified small molecular weight Met-Enk-IR peaks detected without prior enzyme digestion of fractions. The small molecular weight Met-EnkRGL-IR material in rat CSF was found to be comprised of two unknown peptides which were less hydrophobic than Met EnkRGL and its sulphoxide derivative. PMID- 4034408 TI - Competitive antagonists of bradykinin. AB - The first sequence-related competitive inhibitors of the classic kinin in vitro (rat uterus guinea pig ileum) and in vivo (rat blood pressure) assays have been developed. Replacement of the proline residue at position 7 of bradykinin (BK) with a D-phenylalanine residue is the key modification which converts BK agonists into antagonists. [D-Phe7]-BK exhibits moderate (pA2 = 5.0) inhibition of BK activity on the guinea pig ileum but possesses weak BK-like myotropic activity on the isolated rat uterus and 2-4% of BK depressor potency in the rat blood pressure assay. The additional replacement of the phenylalanine residues at positions 5 and 8 of [D-Phe7]-BK with the isosteric beta-(2-thienyl)-alanine residue produces a potent antagonist of BK activity on the uterus (pA2 = 6.4), ileum (pA2 = 6.3), and in the rat blood pressure assay. The antagonism of BK action on smooth muscle is specific for kinins (BK, kallidin, Met-Lys-BK), but neither inhibitor antagonizes the smooth muscle activity of angiotensin or substance P. Inhibition is competitive and fully reversible. PMID- 4034410 TI - Presence of biologically and immunologically active secretin-like substance in the mammalian brain. AB - The present study involves the isolation and characterization of secretin-like immunoreactivity from the brains of pigs, rats and dogs. Secretin-like immunoreactivity was extracted with 0.1 N HCl and subjected to SP-Sephadex ion exchange chromatography and gel filtration on a Sephadex G-50 superfine column. The average amounts of secretin-like immunoreactivity in the extracts of 2 pigs, 7 rats and 6 dog brains were 0.25 ng/g, 2.4 +/- 0.2 ng/g and 0.34 +/- 0.07 ng/g fresh tissue weight, respectively. The secretin-like immunoreactivities in the brain extracts exhibited the same retention coefficient as natural porcine secretin on gel filtration and were eluted in the same salt gradient from the SP Sephadex column. A partially purified secretin-like immunoreactivity isolated from canine brain exhibited the same bioactivity as natural porcine secretin to stimulate pancreatic volume flow in anesthetized rats (n = 4). These results indicated that secretin-like immunoreactivities from brain extracts possess the same molecular size and charge as natural porcine secretin and the secretin-like immunoreactivity isolated from dog brain is active in stimulating pancreatic secretion in anesthetized rats. PMID- 4034411 TI - Presence of immunoreactive neurophysins of a higher molecular weight in addition to the 10.000 form in the ovine pineal gland. AB - Using an aqueous extraction followed by ultrafiltration through Amicon Diaflo membranes, two ovine pineal fractions were obtained, which contain immunoreactive neurophysin. The presence of neurophysin was monitored by radioimmunoassay, employing an antiserum raised against pituitary bovine neurophysin and selected because it reacts with neurophysins of many other mammals. From 50 g of wet ovine pineal glands 552 micrograms of immunoreactive neurophysins were obtained. About 5% of these immunoreactive neurophysins are eluted from three different Sephadex columns with an elution volume corresponding to Mr above 10,000 between bovine serum albumin and pituitary neurophysin. The remaining 95% of ovine immunoreactive pineal neurophysin (Mr 10,000) shares immunological and physico chemical properties with highly purified bovine pituitary neurophysin used as a reference. From the results of gel filtration and affinity chromatography on LVP Sepharose it was concluded that ovine pineal gland may contain a neurophysin precursor molecule in addition to the neurophysin Mr 10,000. PMID- 4034412 TI - Ileo-caecal resection induced pancreatic growth in rats. AB - The effect of ileo-caecal resection on pancreatic growth was studied in rats four weeks after the operation. The results were compared with an identical control group who had undergone laparotomy alone. Pancreatic wet weight in ileo-caecal resectioned rats was 1.4 times greater than that found in control rats. Protein, DNA, RNA contents in the pancreas, pancreatic wet weight per 100 micrograms DNA and RNA/DNA ratio were also found significantly elevated in experimental group as opposed to the control group. Basal plasma levels of cholecystokinin (CCK) and gastrin were measured to delineate the influence of hormonal response on the pancreatic growth in ileo-caecal resected rats and were found not significantly increased after ileo-caecal resection. The data suggest that the enlargement of pancreas in ileo-caecal resected rats may be due to hyperplasia and hypertrophy of pancreatic cells; alternatively, the pancreatic growth may have been influenced by the bile acid deficiency and the reduction or release of an inhibitory factor present in the ileum of rats. PMID- 4034413 TI - Enkephalin pseudopeptides: resistance to in vitro proteolytic degradation afforded by amide bond replacements extends to remote sites. AB - Five analogs of leucine enkephalin containing the CH2S group as an amide bond replacement were evaluated with respect to resistance toward degradation by human serum in an HPLC-based assay using both ultraviolet and electrochemical detection. Analogs with the modification at the 1-2, 2-3, 3-4, or 4-5 peptide linkages demonstrated half-lives of 118, 85, 134, and 318 min vs. 12 min for the parent peptide. A pseudopeptide analog with additional D-Ala2 protection had a half-life of greater than 1000 min, while the potent [D-Ala2]-leucine enkephalin analog showed approximately a 10-fold increase in stability. The significant increase in stability for a compound with protection only at the C-terminus suggests that serum enzymes may have greater specificity toward backbone changes than previously realized. PMID- 4034414 TI - Characterization of alpha-melanocyte-stimulating hormone in rat pancreas. AB - Reverse-phase high performance liquid chromatography and radioimmunoassay were used to characterize alpha-melanocyte-stimulating hormone (alpha-MSH)-like peptides in rat pancreas. Relative to synthetic alpha-MSH standards, serial dilutions of pancreas extracts showed parallel and concentration dependent displacement of (125I) alpha-MSH from alpha-MSH antibody. Chromatographic separation revealed immunoreactive material coeluting with synthetic N,O-diacetyl alpha-MSH, which accounted for 78% of total alpha-MSH materials in this tissue. The remainder of immunoreactive alpha-MSH coeluted with synthetic alpha-MSH, desacetyl alpha-MSH, or their methionine sulfoxides. In contrast with anterior pituitary, it appears that biosynthetic processing of alpha-MSH from pro opiomelanocortin (POMC) may be similar in rat pancreas and pituitary intermediate lobe, since their relative alpha-MSH immunoreactive elution profiles were similar. These findings support the hypothesis of tissue specific regulation of biosynthetic processing of POMC. PMID- 4034415 TI - Unique cholecystokinin peptides isolated from guinea pig intestine. AB - Fractionation on Sephadex G50 gel of methanol extracts of guinea pig intestine reveals two molecular forms of cholecystokinin (CCK) of about equal abundance. One elutes at the position of CCK8 while the other elutes at a position intermediate between CCK33 and CCK8. Purification and sequencing of these peptides identify them as CCK8 and CCK22, respectively. Guinea pig CCK8 differs from other mammalian CCK octapeptides isolated thus far in that there is a valine substituted for methionine at position 6 from the C-terminus. In addition to the substitution in CCK8, serine is substituted for asparagine in position 22, glycine for serine in position 19, and asparagine for serine in position 15 from the C-terminus compared to the pig sequence. HPLC separation on a C18 column yields two peaks each of CCK8 and of CCK22 in pig intestinal tissue obtained from a commercial supplier. The two CCK8 peptides have identical amino acid sequences as do the two CCK22 peptides. The CCK22 peptides are equally bioactive in the guinea pig pancreatic acinar cell assay but are about 10-fold less potent than synthetic CCK8(s). One of the guinea pig CCK8 peptides is fully bioactive whereas the other is about 50-fold less potent compared to synthetic CCK8(s). PMID- 4034416 TI - Treatment of mouse carcinomas with intratumoral injections of hematoporphyrin derivative and red light. AB - Hairless mice with subcutaneously transplanted Lewis Lung carcinomas were used to study the effects of treatments with hematoporphyrin derivative (HPD) administered by intratumoral injection, followed by exposure to red light. A tumor cure rate of 70-90% was obtained following a single treatment. The therapeutic response increased with increasing HPD doses and light fluences. At a certain dose a plateau seemed to be reached, where further dose increase only gave a limited gain in treatment response. A narrow range seems to exist between beginning therapeutic response and frank necrotic destruction. The number of mice that died after treatment increased with increase in tumor size, and there was a correspondence between the time of death and the severity of the phototoxic reactions. The best therapeutic response was obtained when the irradiation was performed 1/2-1 h after injection, and with tumors less than 6-8 mm in diameter. PMID- 4034417 TI - Lack of photorecovery of ultraviolet erythema in human skin. PMID- 4034418 TI - Phytophotodermatitis due to ficus carica. PMID- 4034419 TI - Occupational photosensitivity to dinitrotoluene. PMID- 4034420 TI - Multiform skin eruptions with photodistribution in patients with tularemia. PMID- 4034421 TI - A study of compositae plant extract reactions in photosensitivity dermatitis. AB - In subjects with chronic photosensitivity of the photosensitivity dermatitis/actinic reticuloid type the persistent reaction of the skin appears to be due to a number of factors, including those of contact allergic sensitivity and of photosensitivity (i.e., phototoxicity and/or photoallergy). The assessment of the relevant importance of these factors can be complicated by the reactivity of the skin resulting in false positive responses from skin patch and photopatch testing. Moreover, difficulties may also arise in the assessment of the results using commercially available patch test materials. However, the study described here indicated that, provided the reactivity of the skin is suppressed prior to investigation, reliable results are obtained from photopatch testing and that these results are similar whether the extract is from a commercial source or has been obtained from locally grown Compositae plants. Also, that although there may be a photoallergic component in the cutaneous photosensitivity, the results of the in vivo and in vitro studies reported here indicate the likely involvement of phototoxicity as well. PMID- 4034422 TI - How to avoid phototoxic reactions in photopatch testing with chlorpromazine. AB - The purpose of this study was to determine the concentration, vehicle, and UVA dose suitable for avoiding phototoxic reactions while revealing photoallergic reactions to chlorpormazine (CPZ) in photopatch testing. Photopatch tests were performed on 27 volunteers with CPZ concentrations between 0.05% and 1% in water or Plastibase with UVA doses of 4 or 7 J/cm2. Photopatch tests were also carried out on 1 patient with photoallergic contact dermatitis to CPZ and an increased UVA sensitivity. The same concentration of CPZ caused phototoxic reactions less frequently and less intensely in Plastibase than in water. The minimal phototoxic concentration of CPZ in Plastibase was 0.5% after irradiation with 4 J/cm2 and 0.1% after irradiation with 7 J/cm2. In the patient with photoallergy to CPZ, a photoallergic reaction was elicited after 0.1% CPZ in Plastibase and a UVA dose of 2 J/cm2. In testing photoallergic reactions to CPZ a concentration of 0.1% in Plastibase and a UVA dose of 4 J/cm2 or less should be used. PMID- 4034423 TI - [Late sequelae of cervical spine injuries]. PMID- 4034424 TI - [Locomotive capacity of patients with spinal cord injuries in the thoraco-lumbar segment]. PMID- 4034425 TI - [Pathomechanical analysis of body posture in 11-year-old girls]. PMID- 4034426 TI - [Post-traumatic myositis ossificans]. PMID- 4034427 TI - [First aid and transportation of patients with cranio-cerebral injuries]. PMID- 4034428 TI - Pathology at the crossroads. PMID- 4034429 TI - Ocular myopathies. AB - Ocular myopathies are manifested by primary and progressive involvement of extraocular muscles. In most cases of involvement of extra-ocular muscles a biopsy from somatic muscles studied by histochemistry and electron microscopy permits to make the diagnosis of the underlying condition. The two main clinico pathological types of ocular myopathies are the oculocraniosomatic syndrome (Kearns-Sayre syndrome) and oculopharyngeal muscular dystrophy. The oculocraniosomatic syndrome is a multisystemic disorder and its histopathological hallmark is the presence of ragged-red muscle fibres which contain aggregates of abnormal mitochondria, often with paracrystalline inclusions. In the oculopharyngeal muscular dystrophy are observed muscle fibres with rimmed vacuoles and intranuclear tubular filamentous inclusions about 8.5 nm in external diameter. The rimmed vacuoles may occur in other muscle diseases but the intranuclear inclusions appear to be specific for oculopharyngeal muscular dystrophy. Their nature is unknown. PMID- 4034430 TI - Histological and autoradiographic study on development of group III lesion (dysplasia grade III) in the stomach. AB - In order to elucidate the biological behaviour of the Group III lesion of the stomach, morphogenesis of the lesion was studied from cell kinetic point of view. In most Group III lesions, the proliferative cell zones were found at the upper third level of the mucosa, whereas they were confined to the middle third and to the lower third level in the normal pyloric and in the intestinalized mucosa, respectively. The smallest Group III lesion was a single gland dysplasia, in which the Group III cells were confined to the middle level of the mucosa. These findings suggested that the Group III lesion must be a change initiated in the neck stem cells of the pyloric mucosa as is the case in the intestinal metaplasia. The Group III cells arising at the neck region surge upwards and then accumulate in the upper part of the foveola to form an aberrant proliferative focus from which a lesion develops by budding. This morphogenesis manifests an adenomatous nature of the lesion. However, there was apparently a spectrum of cytological and histological abnormalities which varied from the lesions which might be considered to be a kind of intestinalized tubule, to the typical Group III lesion. Some Group III lesions imitating the intestinal metaplasia contained the proliferative cell zones at the middle level of the mucosa, indicating that a group of the dysplastic tubules arose zonally, not from a single gland. This morphogenesis reflects a metaplastic nature of the lesion. (ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4034431 TI - Morphology and histochemistry of the mucosa surrounding small oligotubular adenomas of the large bowel. AB - The transitional mucosa surrounding adenomas and carcinomas of the large bowel is characterized by a reversion of mucus secretion from sulphomucin to sialomucin and a hyperplasia of crypts and epithelial cells. The specificity of this phenomenon is still a controversial issue. Therefore we studied 72 oligotubular adenomas of the large bowel and the adjacent mucosa by means of histochemistry and morphometry. The peak of sialomucin production is found within the crypts immediately adjacent to the adenoma, whereas the more distant crypts secrete less. The cellular diameter and the depth of the crypts behave in a similar manner, they decrease with increasing distance from the adenoma, still being much higher than in the normal mucosa. The crypt depth correlates well to sialomucin production. The existence of the transitional mucosa around small oligotubular adenomas may indicate, that this mucosal change is not merely secondary to the presence of carcinoma but may be of importance as a precursor lesion of neoplastic changes of the colon and rectum. PMID- 4034432 TI - Association between mitochondria and rough endoplasmic reticulum (rer) in rat hepatocytes. AB - The relative contact area between rough endoplasmic reticulum and mitochondria of hepatocytes in newborn to 27 months old rats is described by morphometric methods. The contact area decreases from 52.62% to 27.46% of the mitochondrial surface between newborn and rats being 27 months old. However, there is an increase in the contact area per hepatocytic cytoplasm and in the fraction of rer in contact with mitochondria during the first days post partum. PMID- 4034433 TI - GFAP in brain tumor diagnosis: possibilities and limitations. AB - Investigation of GFAP (Glial Fibrillary Acidic Protein) in 175 brain tumours showed varying amounts of fibrillary acidic protein in every glioma. In ependymal and oligodendroglial tumours a high number of positive neoplastic elements were detected, GFAP positive were also the peri-vascular cells of a so-called astroblastoma. In pilocytic astrocytomas, Rosenthal fibers were in part GFAP positive, in part negative. In giant cells gliomas, giant cells were GFAP negative or weakly positive. Intraleptomeningeal growing tumour cells presented usually a very strong positivity. In 8 recurring oligodendrogliomas, the number of GFAP positive tumour cells was the same in the primary tumour and in its recurrence. These results demonstrate that GFAP is not a specific astrocytic, but a glial-specific protein. Although GFAP is usually present in greater concentration in differentiated, slow growing gliomas, absolute reliable predictions on biological behaviour of the individual tumour are not possible, because a high GFAP content can be detected also in malignant tumours. GFAP investigation does not seem reliable for solving the pathogenetic problems of undifferentiated tumours: the results obtained in 50 medulloblastomas showed that the investigation of small tumour samples or the positivity of a single cell are inadequate data for a correct evaluation of the findings, especially bearing in mind that GFAP of degenerated astrocytes can be phagocytised by other cells, these findings giving rise to misinterpretations. PMID- 4034435 TI - Tumor, abscess or encephalitis? PMID- 4034434 TI - What's new in Osmosin and intestinal perforation? AB - New formulations of drugs may have unexpected side effects. Osmosin is a new osmotic-pump controlled-release formulation of Indomethacin, designed to prevent gastrointestinal irritation. However, in a small number of cases the use of Osmosin has coincided with perforation of the small and large intestine, probably because passage of the tablet through the gastrointestinal tract was impeded. PMID- 4034436 TI - Collagenous colitis. AB - A clinical and morphological description of "collagenous colitis" with reference to own cases is given. The disease presents with watery diarrhoea and abdominal pain in middle aged subjects, mostly women. Clinical and laboratory findings are normal. In colo-rectal biopsies there is a severe thickening of the so called "collagen table" in the superficial inter-cryptal lamina propria. Ultrastructural examination shows bandlike subepithelial collagenous fibrils of types I and III. The etiology of this lesion in the large bowel is hitherto unknown. The clinical course seems to be rather benign, requiring only symptomatic treatment. PMID- 4034437 TI - A search for a model of experimental atherosclerosis: comparative studies in rabbits, guinea pigs and rats. AB - Rabbits, guinea pigs and rats received for 3 months a high lipid diet containing coconut oil and cholesterol, separately or in combination. The blood lipid content was assayed. Lipoproteins were separated into fractions by agarose electrophoresis. The aorta, heart and liver were investigated macro- and microscopically. The most pronounced changes in lipid metabolism appeared as a consequence of combined administration of coconut oil and cholesterol; they were most expressed in rabbits, less in guinea pigs, and most weakly in rats. Typical atherosclerotic lesions were observed only in rabbit's aorta. They were accompanied by a marked depression of the percentage content of alpha lipoproteins in blood serum. PMID- 4034438 TI - Synthesis of alpha-aminomethyl derivatives of beta-phenyltetrahydrofuran-2-one. AB - beta-Phenyltetrahydrofuran-2-one-alpha-carboxylic acid 1 was transformed in the Mannich reaction into alpha-aminomethyl derivatives of beta-phenyltetrahydrofuran 2-one 2-6. The obtained alpha-aminomethyllactones, in reaction of ammono- and hydrazinolysis yield alpha-aminomethyl-beta-phenyl gamma-hydroxybutyric acid derivatives 7-12. Compounds 4, 5, 8, 9, and 10 depress the central nervous system, and compound 12 shows analgesic properties. PMID- 4034439 TI - Benign isolated histiocytosis mimicking chicken pox in a neonate: report of two cases with ultrastructural study. AB - Two cases of benign isolated cutaneous histiocytosis X in newborn infants are reported. Clinically, the lesions mimicked chicken pox, and the histologic findings in skin biopsies were indistinguishable from those described in infantile Letterer-Siwe disease. Electron microscopy showed Langerhans' cells with the classical trilaminar, racket-shaped granules. Our cases a well as 10 of the 21 previously reported cases showed spontaneous resolution of the skin lesions. Since this is a benign spontaneous resolving histiocytosis, we recommend that no therapy be given provided that no other signs of systemic involvement are found. PMID- 4034440 TI - Familial hemophagocytic lymphohistiocytosis: report of four cases in two families and review of the literature. AB - Four cases of familial hemophagocytic lymphohistiocytosis (FHL) from two families with first cousins affected in family and siblings in another are presented. The pathological findings, including neuropathology, transmission (TEM), and scanning electron microscopy (SEM), are discussed. This is the first study of this condition to include TEM and SEM. One hundred and fifty-nine cases from the literature, including the author's four cases, are reviewed. The familial occurrence in 116 instances in sibships and consanguinity in 13 of the 73 families support autosomal-recessive inheritance. In five families there were affected first cousins--an observation not readily explained by autosomal recessive transmission. We suggest that the genetic aspects of FHL be more fully explored and that in future cases parents and other relatives be included in the hematologic, immunologic, and genetic evaluation. PMID- 4034441 TI - [The methods and possibilities of studying experimental radiation injuries of the digestive tract]. PMID- 4034442 TI - Otitis externa. A common, often self-inflicted condition. AB - Otitis externa can be caused by trauma to the ear canal, skin disorders, and viral and bacterial infections. Often the disease is self-inflicted; insertion of an object into the canal in an attempt to clean the ear interferes with the ear's own cleansing mechanism and causes inflammation and infection. Swimmers, persons who wear a hearing aid, and persons who have had an ear disorder are especially prone to infection and may need to take special precautions. Appropriate treatment, including instillation of drops, cleansing of the canal, and drug therapy, usually prevents recurrence. Surgical intervention may be necessary to enlarge a tiny canal or remove exostoses and osteomas. A rare form of otitis externa is "malignant" external otitis, which usually affects diabetic patients and has a high mortality. PMID- 4034444 TI - Mitral valve reconstruction. An underused alternative to replacement. PMID- 4034443 TI - Aspirin sensitivity in asthmatics. When may this drug be safe? PMID- 4034445 TI - Contraception for the adolescent. AB - The primary care physician is in an excellent position to counsel adolescents about contraception. However, an adequate understanding of the biologic and psychosocial development of this particular age-group is imperative. In addition, communication skills are necessary to advise adolescents on use of contraceptives. The goal in counseling the adolescent about sexuality is to instill a sense of sexual responsibility and to provide individualized instruction in selecting the appropriate birth control method. General factors to remember in selecting the proper method include motivation, moral-ethical responsibility, frequency of intercourse, side effects of the various contraceptive methods, and patient's preference. PMID- 4034447 TI - Space-age snake oil. Obesity and consumer fraud. PMID- 4034446 TI - Adult-onset muscle weakness. How to identify the underlying cause. AB - When adults present with muscle weakness as the predominant symptom and sign, the causes can usually be narrowed down to four disorders: amyotrophic lateral sclerosis, Guillain-Barre syndrome, myasthenia gravis, and inflammatory myopathy. Perhaps the most difficult task for the clinician is identifying which of these patients are actually weak and which are describing generalized fatigue. This task should be made easier by keeping in mind the definition of muscle weakness- a loss of power resulting in reduction of motor function--and by performing careful functional muscle testing. PMID- 4034448 TI - Don't overlook 'little' things. PMID- 4034449 TI - Flexible sigmoidoscopy for screening in primary practice. A key to improved survival in colon cancer. AB - Numerous recommendations have been made in recent years regarding periodic screening for colon disease, specifically cancer. Early detection and treatment are essential for improved survival rates, and patient education is the key to success. Important factors in a screening test are reasonable cost and ease of performance. Testing for fecal occult blood fulfills these requisites but lacks specificity. Digital rectal examination should be done regularly but has limitations. Because flexible fiberoptic sigmoidoscopy has a high acceptance rate, low complication rate, and high yield and is relatively easy to perform, this procedure should be in the diagnostic armamentarium of all primary care physicians. Results of 129 flexible sigmoidoscopies performed by primary care physicians at Scripps Clinic indicate the usefulness of this procedure as a screening test for colon cancer. PMID- 4034450 TI - Cancer surveillance. Who stands to benefit? AB - Currently, surveillance or risk-oriented follow-up of patients in the individual practice setting may be the most efficacious means of reducing the morbidity and mortality associated with selected types of cancer. Intervention into carcinogenesis or alteration of the natural history of cancer requires a clear understanding of the pathogenesis of the disease and patient acceptance of interval surveillance. Because etiologic information and patient compliance are frequently limited, careful scrutiny of recommendations for cancer screening or prevention is essential. It is through taking detailed family, occupational, and carcinogen-exposure histories and doing a thorough physical examination that the primary care physician can best utilize information regarding the risk of cancer and the benefits of available methods of prevention and treatment. PMID- 4034451 TI - Ocular and oral problems in arthritis. How to recognize, when to refer. AB - Recognition of oral and ocular problems is important in the management of arthritis. Although the focus of attention is usually on joint problems, patients with these chronic disorders require a comprehensive approach to their total medical care. Physicians need to watch for physical signs of significant inflammation and should alert their patients to watch for significant symptoms. PMID- 4034452 TI - Drug abuse in adolescents. When to intervene, how to help. AB - Abuse of alcohol and other drugs by adolescents is a major societal problem. For many adolescents, drug use signals departure from childhood and acceptance by peers. Diagnosis is often difficult and depends on a high index of suspicion and an understanding of the typical clinical and psychological course of drug use. Family involvement in treatment is vital and directly affects recovery rates of adolescent drug abusers. An effective treatment program insists on abstinence, and peer group involvement is extremely valuable. Careful follow-up is essential to prevent or detect relapse. PMID- 4034453 TI - Bureaucracy in medicine. Is there an alternative. PMID- 4034454 TI - Oncologic emergencies in primary care. Five malignancy-associated conditions to watch for. AB - Acute problems requiring emergency management may occur in association with malignancy. The most common are superior vena cava syndrome, compression of the spinal cord or cauda equina, hypercalcemia, tumor lysis syndrome, and fever in the neutropenic patient. Successful management requires that the physician be aware of the potential for such an emergency in a cancer patient and give priority to treatment, based on clinical evidence and a few essential studies, over definitive diagnosis. PMID- 4034455 TI - Nerve blocks and chronic pain states--an update. 1. Basic considerations. AB - Appreciation of the extremely complex nature of pain has resulted, regrettably, in diminished use of nerve blocking to manage chronic pain states. Nevertheless, clinical use of these time-honored techniques remains popular in clinical anesthesia for surgery, in obstetrics, and in the control of pathogenic pain resulting from injury or disease. Patients with chronic pain are best assessed by cross-matched analysis of medical, emotional, and social factors. PMID- 4034456 TI - Nerve blocks and chronic pain states--an update. 2. Clinical indications. AB - With the unfortunate exception of the differential spinal block, diagnostic nerve blocking has become somewhat obsolete with the development of newer, more sophisticated diagnostic technology. Therapeutic nerve blocks remain useful in treating patients with various terminal cancers, some forms of back pain, tic douloreux, causalgia, reflex sympathetic dystrophy, and many trigger point syndromes. For dysfunctional and pain-disabled patients (rated as class 1 or 3 on Emory Pain Estimate Model), block therapy must be structured in comprehensive pain rehabilitation programs. PMID- 4034457 TI - Non-invasive assessment of early cardiac involvement in systemic sclerosis. AB - Twenty-eight patients with wide spectrum organ involvement of progressive systemic sclerosis but without signs or symptoms suggestive of cardiac involvement were studied by non-invasive cardiac techniques. The 12-lead electrocardiogram showed abnormalities in 6 patients: one had abnormal T waves and 5 had complete or incomplete right bundle branch block. Twenty-four hour ambulatory electrocardiography demonstrated higher average heart rates than in similar aged controls (82 +/- 9 vs 74 +/- 9 beats/min, P less than 0.05). In one patient a short run of ventricular tachycardia was recorded. No other significant arrhythmia was documented. Echocardiographic measurements were within normal ranges but small pericardial effusions were observed in two patients (7%). Resting first pass radionuclide angiography, utilizing 12 mCi of technetium 99m were performed in 23 patients. Seven patients (30%) had abnormal wall motion (diffuse hypokinesia), with a significant decrease in ejection fraction in comparison to those with normal wall motion (44 +/- 6% vs 60 +/- 6% P less than 0.01). Those with abnormal wall motion had suffered the disease longer than those with normal wall motion (13 +/- 4 vs 9.5 +/- 7 y). In conclusion, the heart is involved in half of the patients in this series; non-invasive cardiac assessment is useful in disclosing the early cardiac involvement and may influence long-term management. PMID- 4034458 TI - Pyoderma gangrenosum in myelodysplasia and acute leukaemia. AB - Pyoderma gangrenosum is a rare occurrence in patients with haematological malignancy. This characteristic but nonspecific inflammatory process with skin destruction occurred in 4 patients with myelodysplasia, in one with acute leukaemic transformation of myelofibrosis, and in de novo acute myeloblastic leukaemia in another. Clinically, the cutaneous lesion in these patients differed from that associated with inflammatory bowel disease, arthritis, or the idiopathic type of pyoderma gangrenosum by having the vesiculo-bullous borders. Histopathological differences were also evident since more superficial layers of the skin were involved in the ulceration than typically encountered in patients with non-malignant systemic disease. Despite the less penetrating nature of this variant, treatment of the pyoderma gangrenosum is unsatisfactory and in the absence of effective therapy for the underlying disease, healing occurred only in the patient with acute leukaemia who achieved complete remission in response to chemotherapy. PMID- 4034459 TI - Benign gastric ulceration in a health district: incidence and presentation. AB - In a survey of benign gastric ulceration conducted in the Hounslow Health District from 1981 to 1982, there was an annual incidence for this condition of 43.6 per 100,000 of the population older than 14 y, with a male:female ratio of 0.9:1. This incidence is comparable to that found in other surveys over the last 30 y, but the male:female ratio is lower than in the past. This reduction is accounted for by a rise in the peak age incidence for gastric ulcer, particularly in women, and a greater proportion of the total population in this higher age group being women. In spite of a large local Asian population, no gastric ulcers occurred in this ethnic group. Thirty-eight per cent of the patients presented with acute bleeding, and 44% of these bleeders gave a history of previous ingestion of non-steroidal anti-inflammatory drugs compared with only 14% of the non-bleeding group (P less than 0.015). PMID- 4034460 TI - The clinical value of Haemoccult and Fecatwin in the detection of colorectal neoplasia in hospital and general practice patients. AB - Four hundred and fifty asymptomatic general practice patients and 330 hospital inpatients had their stools tested for occult blood with the Haemoccult and Fecatwin methods. In general practice, 9/64 (14%) of patients with a positive result had a colonic neoplasm (three carcinomas, one Dukes' Stage A, two Dukes' Stage C, six adenomas) and in hospital 12/142 patients (8%) were found to have colonic tumours, (nine carcinomas, two Dukes' Stage A, two Dukes' Stage B, five Dukes' Stage C and three adenomas). The overall detection rates for colonic neoplasia were 2% in general practice and 3.4% in hospital. In 2 years of follow up, none of the general practice patients have presented with colonic symptoms. Two hospital patients with colonic carcinomas produced negative tests with both methods. Out of the total of 21 colonic neoplasms, nine were detected by Fecatwin alone, but this trend in favour of the more sensitive test did not reach the 5% level of statistical significance. In contrast, the number of false positive results were significantly greater with Fecatwin than Haemoccult. From our data it would appear that the Fecatwin method warrants assessment in a full controlled trial of its value as a population screening test for colonic cancer. PMID- 4034461 TI - Clinical diagnosis: a post-mortem assessment of accuracy in the 1980s. AB - The clinical diagnoses of a series of 400 patients dying in hospital were compared with the pathological findings at autopsy. The clinical diagnoses were precisely confirmed in only 46.75% of cases (average age 65.3 y). Potentially treatable disease was missed in 13% of patients (average age 72.7 y). The most frequent errors, both of under-diagnosis and over-diagnosis, were for pulmonary embolus, pneumonia and myocardial infarction. Over-diagnosis increased with length of hospital stay. Peritonitis and other deep-seated sepsis were surprisingly frequently missed in life. The findings closely parallel those from other units both in Britain and overseas, and suggest that there is currently a high diagnostic error rate, which varies remarkably little from one institution to another. PMID- 4034462 TI - Pseudo-phaeochromocytoma due to alcohol withdrawal. AB - Alcohol withdrawal hypertension is a common clinical problem which often goes unrecognized. We report a case in which the symptoms and signs of withdrawal with a marked elevation in blood pressure mimicked the features of a phaeochromocytoma. Despite a positive phentolamine test no further evidence for phaeochromocytoma was found and both blood pressure and symptoms settled as the features of alcohol withdrawal abated. PMID- 4034463 TI - Diaphragmatic myasthenia in mother and child. AB - A 28 year old patient with ocular myasthenia for 2 y gave birth to a baby with diaphragmatic weakness. Following delivery the mother developed severe weakness of the diaphragm and required assisted ventilation. The baby recovered spontaneously and the mother responded to treatment with plasma exchange and immunosuppression. Neither mother nor baby responded to anticholinergic drugs and in neither serum were acetyl choline receptor antibodies detected. PMID- 4034465 TI - Anti-arthritic propionic acid derivatives and 17-oxosteroid measurements--a direct interference. AB - Many drugs interfere with the assay of urinary 17-oxo and oxogenic steroids. Some propionic acid derivatives, in particular, tiaprofenic acid, have now been shown to affect this assay. Care should be taken when interpreting results in patients on these drugs. PMID- 4034464 TI - Bilateral primary malignant lymphoma of the breast. AB - A rare case of bilateral primary malignant lymphoma of breast in a 76 year old woman is presented. The lesion was examined by electron microscopy and immunochemistry. The diagnosis of primary malignant lymphoma remains a diagnosis by exclusion and requires extensive work-up to exclude widespread malignant process. The behaviour of this malignancy tends to be an aggressive one and the prognosis is generally poor. PMID- 4034466 TI - Reversibility of acute renal failure in elderly patients with the nephrotic syndrome. AB - Acute renal failure may occur in the nephrotic syndrome due to minor glomerular changes, especially in the elderly. We describe five cases and review the literature. Previous renal damage due to ischaemia and drugs may be important in pathogenesis. We stress the importance of active management of these cases, as the renal lesions are reversible and recovery can be expected. PMID- 4034468 TI - Remission of life-long atopic dermatitis after hyposensitisation to house dust mite. PMID- 4034467 TI - Fetal heart rate variation with umbilical haematoma. AB - Umbilical cord haematoma is an infrequent condition associated with high perinatal and fetal mortality and morbidity. This report describes a rare case of umbilical cord haematoma associated with loss of fetal beat to beat variation during labour. The infant exhibited mild asphyxia only. Previous publications are reviewed and fetal heart rate changes associated with umbilical cord haematoma are discussed. PMID- 4034469 TI - Stroke patients successfully rehabilitated. PMID- 4034470 TI - Screening for thyroid disorders in general practice. PMID- 4034471 TI - Child consultation rates in service families. A comparison with civilians. PMID- 4034472 TI - Bronchodilator therapy in general practice--what are the problems? PMID- 4034473 TI - Treatment of psoriasis in general practice with short contact dithranol. PMID- 4034474 TI - Experience with microcomputers in general practice. PMID- 4034475 TI - Patient and doctor preferences in the treatment of vaginal candidosis. PMID- 4034476 TI - Normal pressure hydrocephalus. PMID- 4034477 TI - Occupational photodermatitis from parsley. PMID- 4034478 TI - Preparation for surgery: information tapes for the patient. PMID- 4034479 TI - Change of clinical attitude urged in hypertension. PMID- 4034480 TI - Practice nurses have important role in asthma. PMID- 4034481 TI - An unusual presentation of acute appendicitis. PMID- 4034482 TI - Preconception care. PMID- 4034483 TI - Computers in obstetrics. PMID- 4034484 TI - Antenatal diagnosis of genetic disease. PMID- 4034485 TI - The present position on in vitro fertilisation. PMID- 4034486 TI - A treatment of herpes zoster. PMID- 4034487 TI - [Cardiac therapy in acute pneumonia]. PMID- 4034488 TI - [Trainability of respiratory muscles in patients with obstructive respiratory tract diseases]. PMID- 4034489 TI - [Comparative study of the work of breathing and airway resistance]. PMID- 4034490 TI - [Clinico-pharmacologic aspects of prescribing theophylline-containing preparations]. PMID- 4034491 TI - [Occurrence of bronchial obstruction in asthma patients immediately following administration of timolol-containing eyedrops]. PMID- 4034492 TI - [Necrotizing sarcoid granulomatosis of the lung]. PMID- 4034493 TI - [Families with psychosomatically ill children. Study of family dynamics in bronchial asthma and ulcerative colitis]. PMID- 4034494 TI - [The colitis family in the Rorschach Test]. PMID- 4034495 TI - [Treatment of mother and child. The neurotic index group]. PMID- 4034496 TI - [Unresolved grief in colitis and asthma families. A contribution to a 3 generation perspective]. PMID- 4034497 TI - [Statements of parents about their children. Comparative study based on results of 2 questionnaires (Diagnostic Parent Questionnaire and Giessen Questionnaire for Parents in Clinical Complaints) on the development of the children and their current behavior]. PMID- 4034498 TI - [Psychoanalysis and family dynamics]. PMID- 4034499 TI - [Families with a child ill with colitis or asthma in the initial psychoanalytic consultation and the family Rorschach Test]. PMID- 4034500 TI - [Development of a family evaluation questionnaire]. PMID- 4034501 TI - [Children in family therapy. System theoretical and psychoanalytic reflections]. PMID- 4034502 TI - [Development of psychosomatic disease. Status of research and expectations of family psychosomatization]. PMID- 4034503 TI - [Significance of historical family research for family therapy]. PMID- 4034504 TI - [Family dynamics in a case of bronchial asthma]. PMID- 4034505 TI - [Introduction to inpatient child and adolescent psychiatric treatment by the initial family interview]. PMID- 4034506 TI - [Psychotherapy of puberal anorexia nervosa from the viewpoint of cognitive theories]. PMID- 4034507 TI - [Coping behavior in children with encopresis]. PMID- 4034508 TI - An apparatus for the concentration of large volumes of dilute protein solutions to a predetermined volume. AB - An apparatus was designed and manufactured that can be used for the concentration of large quantities of dilute protein solutions to a predetermined volume. The method is based on the osmotic transfer of water to a concentrated hydrophilic polymer (poly ethylene glycol, PEG) through a protein-stopping dialysis membrane and is a refinement of a method previously reported by van Oss. The apparatus is made of perspex. Concentration takes place through a commercially available dialysis tube and is aided by a 40% polyethylene glycol solution. Large volumes (5l) of dilute protein solution could be reduced to 50 ml at a rate of 30 ml per hour with no significant loss in biological activity. PMID- 4034509 TI - Biosynthetic incorporation of cis-parinaric acid into radioactive sn-3 phosphatidic acid. AB - Isolated guinea pig liver microsomal membranes catalyzed the incorporation of naturally occurring cis-parinaric acid into sn-3-[U-14C]glycerophosphate. This resulted in the formation of sn-3-[14C](parinaroyl)phosphatidic acid, which was isolated by Chelex-100 and DEAE-cellulose column chromatography and further purified by Sephadex-G 25. The sn-3-[14C](parinaroyl)phosphatidic acid thus obtained exhibited absorption and fluorescence spectra substantially different from the cis-parinaric acid. Distribution of the incorporated cis-parinaric acid between the hydroxyl groups of biosynthesized sn-3-[14C]phosphatidic acid was determined by degradation with Crotalus adamanteus venom. This established that the major portion of the incorporated cis-parinaric acid esterified the secondary hydroxyl group in the sn-3-[14C]phosphatidic acid, while the primary hydroxyl group was esterified to a significantly lesser degree. The similarity between the biochemical incorporation of isomeric doxyl stearic acids into lipids of biological membranes and that of cis-parinaric acid into sn-3-phosphatidic acid described in this communication are discussed in relation to the possible use of these probes in studies of intact biological membranes. PMID- 4034510 TI - Alcohol consumption and blood pressure: analysis of data from the Canada Health Survey. AB - Recent epidemiologic studies report a significant association between alcohol consumption and elevations in both systolic (SBP) and diastolic (DBP) blood pressures. To test this hypothesis, we conducted a multivariate analysis of physical examination and other data on 721 men and 697 women aged 20 or more collected during the Canada Health Survey in 1978-1979. SBP and DBP were considered as separate dependent variables in multiple regression models with the following independent variables: age, alcohol consumption (measured as a 7-day recall history and as an average frequency of consumption), serum cholesterol, plasma glucose, physical activity, Quetelet index, parental history of hypertension, cigarette consumption, income, education, and exogenous hormonal use in women. In both weighted and unweighted multiple regression analyses, we could not demonstrate for either sex, a significant association between alcohol consumption (as recorded and following quadratic and logarithmic transformations) and either SBP or DBP. For both sexes, only age and Quetelet index were highly significantly (P less than 0.0001) and consistently associated with both SBP and DBP. No other independent variables were consistently associated, for either sex, with SBP and DBP. Further, the dose-response patterns noted by other investigators suggesting either a positive and linear relationship or a curvilinear relationship were not found in either our univariate or multivariate analyses. Rather, the alcohol-blood pressure curves showed no consistent patterns of any kind in either sex. These findings do not support recent claims that alcohol consumption is a determinant of elevations in either SBP or DBP. PMID- 4034511 TI - A hypertension treatment program at the workplace to complement community care. AB - A worksite hypertension control program was established for employees of the state of Maryland. Employees were screened for hypertension, and individuals identified as hypertensive were encouraged to seek care from community physicians. For those choosing not to seek such community care, a treatment program was initiated at the worksite. Of the 417 hypertensives identified, 54 (13%) elected to have their blood pressure treated at the worksite. Comparisons between the group choosing worksite care and the group choosing community care revealed that the worksite group was generally a higher risk group by virtue of having less awareness of their hypertension, being less likely to be on antihypertensive treatment, and being less likely to have their hypertension controlled by medication. This group made relatively little use of community physicians. Increases in hypertension treatment and control were greater in the worksite group after a 2-year follow-up examination. The project suggests an important role for worksite treatment programs for hypertension as a complement to existing community care. PMID- 4034512 TI - Personality as a moderator of the effects of cigarette smoking on coronary risk. AB - This study pursues an earlier investigation by G. D. Friedman et al. [Prev. Med. 12, 533-540 (1983)] which reported that a group of psychological questions moderated the effects of cigarette smoking on myocardial infarction. In a group of 65 smokers drawn from a study of 278 middle-aged men it is shown that, among smokers, the personality dimension entitled dependence/independence appears to have a significant moderating effect on the relationship between the amount smoked and the elevations of diastolic blood pressure, cholesterol, triglycerides, and uric acid. It is suggested that the moderating effects of this personality dimension, which is sometimes called "Promethean Will," and which appears similar to the concept of hardiness introduced by S. C. Kobasa [J. Pers. Soc. Psychol. 37, 1-11 (1979)] may be attributable to either the differential effect of coincident dietary behavior or variation in sympathetic response. It is noted that this type of investigation may provide greater insight into how cigarette smoking affects coronary risk, and it is suggested that a potentially interesting future investigation would examine whether, among smokers, such personality dimensions have associated dietary effects or might moderate the relationship between the amount smoked and catecholamine response. PMID- 4034513 TI - Multivariate evaluation of health attitudes and behaviors: development and validation of a method for health promotion research. AB - Many self-reported measures of health status, attitudes, and knowledge used by clinicians and researchers suffer from a variety of shortcomings, including limited empirical justification, excessive complexity, assessments of nonmodifiable historic or hereditary factors, and limited utility for public health program planning. The Health Attitudes and Behavior Scale is an instrument designed to overcome many of these shortcomings and direct public health professionals toward more efficacious interventions. One hundred sixty-four subjects responded to true-false and Likert scale items related to health beliefs, attitudes, and behavioral practices. A principal component analysis of the Likert items yielded six components, tentatively labeled (a) Lack of Social Support, (b) Hurdles to Health, (c) Health Attitudes/Weight Concerns, (d) Positive Environment, (e) Disease Concerns, and (f) Time and Work Pressure. Analyses of these scales using coefficient alpha indicated adequate internal consistency for each of them. These scales were then related to demographic variables of age, educational level, sex, and marital status. Next, these scales were correlated with individual true-false items reflecting self-reported behavioral practices or health histories. A component analysis of the true-false items yielded four principal components labeled (a) Organizational Health Concerns, (b) Smoking and Exercise Concerns, (c) Coronary and Weight Concerns, and (d) Blood Pressure and Risk Factor Programs. Finally, a cluster analysis yielded six typical profiles reflecting different levels of the original six components. Of interest is the fact that the Lack of Social Support and Time and Work Pressure scales had a very limited integration into the overall patterns. The assumption that organizational and environmental factors can have an important impact on health was supported. The need for further research in this area is also discussed. PMID- 4034514 TI - Relative sensitivity of the fecal occult blood test and flexible sigmoidoscopy in detecting polyps. AB - A group of 1,002 male pattern and model makers, an occupational group at high risk for colorectal cancers, was screened for the presence of polyps and malignancies of the lower gastrointestinal tract. Flexible sigmoidoscopy and serial fecal occult blood testing were both performed on 988 of the participants, and 165 were found to have at least one colorectal polyp. Only 3% of all men with visualized polyps showed Hemoccult-positive stools. Only 2 (4%) of the 51 men with histologically proven adenomatous polyps were Hemoccult positive. Adenomatous polyps of 1 cm or greater in diameter are malignant 8% of the time. This study concludes that the fecal occult blood test sensitivity in detecting colorectal polyps is unacceptably low. It should be supplemented by more rigorous procedures, especially in populations at high risk for colorectal cancer. PMID- 4034515 TI - An epidemiologic study of the carpal tunnel syndrome in an adult female population. AB - The relationships between certain reproductive, demographic, and medical variables and the carpal tunnel syndrome were examined using data from a hospital based case-control study of women ages 45 to 74 years in the New Haven and Hartford, Connecticut, areas from 1977 to 1979. Characteristics of 40 carpal tunnel syndrome cases and 1,043 controls from hospital surgical services were compared. A history of diabetes was associated with an increased frequency of occurrence of the carpal tunnel syndrome, a finding consistent with clinical observation. Recent weight gain and use of estrogen replacement therapy were identified as possible risk factors; this provides some support for the theory that fluid retention in the soft tissues of the carpal tunnel is etiologically involved, although these results are preliminary and further research must be carried out to refute or support these findings. The negative association of the carpal tunnel syndrome with height and a history of varicose veins and the positive association with age at menopause cannot be explained and need verification. PMID- 4034516 TI - Attitudes and practices of physicians regarding hypertension and smoking: The Stanford Five City Project. AB - A survey was sent to 318 physicians in Monterey County, California, to assess their attitudes and practices regarding hypertension and cigarette smoking. After three mailings, 62% returned completed questionnaires. Eight percent of the respondents were smokers, 5% were women, and 34% were in primary care specialties. Older physicians and primary care specialists were less aggressive in their treatment of high blood pressure, but none of the assessed attitudes was significantly associated with treatment practice. Only half of the sample advised all patients to quit smoking. Physicians who doubted the effectiveness of their anti-smoking advice or who did not know what to say to smoking patients were less likely to provide advice. Most physicians felt that their smoking patients lacked sufficient motivation to quit. Programs to encourage physicians to increase smoking cessation activities should address these attitudes. PMID- 4034517 TI - Cigarette smoking, tumor recurrence, and survival from bladder cancer. AB - Results are presented from an investigation into the effects of cigarette smoking on tumor recurrence and survival in a group of 302 patients with bladder cancer. A regression analysis using Cox's proportional hazards model was done to evaluate the effect of cigarette smoking status, stage of disease at diagnosis, histology, race, sex, and the patient's age at diagnosis on length of survival. Results showed that younger patients, those with less extensive disease, and those with transitional cell tumors showed the best survival. Cigarette smoking was unrelated to survival. The effects of cigarette smoking on tumor recurrence were examined in patients with localized disease. Smoking status was not associated with either recurrence-free survival or the number of tumor recurrences. These findings suggest that cigarette smoking is not an important prognostic factor for patients with bladder cancer. PMID- 4034518 TI - Health promotion at the worksite. I. A process for establishing programs. AB - A 14-step process for establishing health promotion programs at the worksite is described. During a period of 3 years, it has been used to establish 58 such programs in 12 small industries that employ 4,200 persons in a rural county in Pennsylvania. Few problems have been encountered; the most serious is the very limited record-keeping system of industries. The process is flexible and can be readily generalized to different settings. The major strengths of the process are the sense of ownership it gives to employees, and the modesty of its costs and the costs of the resulting programs. PMID- 4034519 TI - Morphological variations on the dorsal surface of the human tongue. PMID- 4034520 TI - [Role of the mandibular condyle in facial growth]. PMID- 4034521 TI - [Flow rate, pH, and lactobacillus and yeast counts of stimulated whole saliva in adults]. PMID- 4034522 TI - Presence of primary teeth in a series of Finnish children. PMID- 4034523 TI - Cephalometric comparisons of the cranial base and face in children with the Pierre Robin anomalad and isolated cleft palate. PMID- 4034524 TI - Anomalies in the deciduous dentition outside the cleft region in children with oral clefts. PMID- 4034525 TI - Histomorphological findings in dentine in nonlethal Osteogenesis imperfecta. PMID- 4034526 TI - The effects of atrial fibrillation on myocardial blood flow and energetics. AB - The changes produced by atrial fibrillation on myocardial blood flow and energetics are unclear. Accordingly, the effects of atrial fibrillation on myocardial blood flow and oxygen consumption were studied in 18 anesthetized dogs. With atrial fibrillation cardiac output and mean aortic pressure declined. Although average myocardial blood flow and oxygen consumption did not change, the alterations in these variables correlated strongly (r = 0.95, P less than 0.01). Moreover, myocardial blood flow changes correlated with those of tension time index and peak dp/dt (r = 0.64, P less than 0.05). Distribution of left ventricular regional flow remained uniform irrespective of the directional changes in blood flow. However, average left ventricular inner to outer wall flow ratio declined and myocardial oxygen extraction increased. Thus, with atrial fibrillation, myocardial blood flow does not change in a consistent fashion, although myocardial blood flow still reflects myocardial oxygen demand. Relative hypoperfusion of subendocardium and an increase in myocardial oxygen extraction suggest that with atrial fibrillation the myocardial blood flow response is abnormal. PMID- 4034527 TI - The relationship between plasma fibronectin levels and autoimmune disease activity in MRL/l mice. AB - Plasma fibronectin levels increased significantly over time in MRL/l mice with progressive autoimmune disease. At 100 and 120 days of age both male and female MRL/l mice exhibited significantly higher fibronectin (Fn) levels than the more resistant MRL/l controls. Male mice at early time points had Fn levels no greater than controls due perhaps to the later onset of disease in MRL/l males. In contrast, female MRL/l mice, when compared with MRL/n controls, had higher Fn levels from 40 days of age. The proteinuria in these animals was also above MRL/n controls from the first time point taken (Day 40). In a temporal study with female MRL/l mice, Fn levels peaked at age 120 days and reflected the pattern of the survival curve, indicating that plasma Fn levels have an association with disease activity. PMID- 4034528 TI - Blood parameters and body composition in fetuses from reciprocal crosses of genetically lean and obese swine. AB - Lines of swine previously selected for either high backfat (obese) or low backfat (lean) were investigated to determine the effect of maternal obesity and the relationship between serum parameters and body composition. Fetal weight, percentage body protein, fat, fat-free organic matter and ash, and serum concentrations of albumin, growth hormone, triiodothyronine, and cortisol were compared in fetuses from straight line and reciprocal crosses at 110 days of gestation. Fetuses from the obese line weighed less but had a greater percentage body protein, fat, and fat-free organic matter than did fetuses from the lean line. Serum concentrations of albumin and triiodothyronine were less whereas those of growth hormone were greater in fetuses from the lean line compared to fetuses from the obese line. Values for these parameters in fetuses from the reciprocal crosses were generally intermediate to those of fetuses from the lean and obese lines. Comparisons of fetuses from the reciprocal and line crosses by linear contrast showed that the observed differences were mainly due to the average genetic effect of individual fetal genotypes and not due to maternal effects. Correlations computed from the residual variance showed a positive relationship between percentage body protein, serum albumin, and triiodothyronine while percentage body fat was not correlated with any of the other traits. Serum growth hormone was negatively correlated with fetal weight. We conclude that there is no apparent maternal effect of obesity or relationship of fetal fat content with any of the other variables measured in these lines of swine at the stage of fetal development at which these determinations were made. PMID- 4034529 TI - Unique effects of spindle inhibitors on mammalian oocyte meiosis. AB - The effects of Nocodazole, reported to be a rapidly reversible inhibitor of microtubules in somatic cells (1), and Colcemid, a classic microtubule inhibitor, were studied for their effects on mouse and cow oocyte in vitro meiotic resumption. When present throughout the maturation period to Metaphase II/Polar Body I, both compounds predictably inhibited progression at Metaphase I (MI). An unexpected effect was seen on mouse germinal vesicle breakdown (GVB) with both inhibitors, but not in cow oocytes tested with Nocodazole. Recovery from Nocodazole was notably retarded in mouse oocytes even with brief exposure times. Addition of 1 microgram/ml of Nocodazole 10 min after commencement of mouse and cow oocyte incubation was sufficient time to allow normal GVB, while inhibition at MI still took place suggesting that the critical events of GVB occur very quickly in vitro. PMID- 4034530 TI - Teratocarcinoma cells cultured on embryonic substrates show accelerated migrating behavior in vitro and increased metastatic activity in vivo. AB - Teratocarcinoma cells (402AX) were grown on feeder layers of whole mouse embryos (Day 4) or mouse embryonic fibroblasts and then were either examined in vitro or transplanted in vivo. After twenty-four hours of coculture, teratocarcinoma cells demonstrate accelerated cell migration in vitro. Furthermore, transplantation of teratocarcinoma cells with embryonic substrates into syngeneic hosts produces grossly detectable lymph node metastases. These effects appear to be due to soluble factor(s) produced by embryonic substrates which enhance tumor cell proliferative/migratory activity. This suggests that tumor cell invasion and metastasis may be stimulated by soluble factors produced by host tissues. PMID- 4034531 TI - Influence of selenium on the growth of N-nitrosomethylurea-induced mammary tumor cells in culture. AB - Selenium is an essential dietary trace element which has anticancer properties. Among its effects in rats, selenium has been shown to inhibit the development of carcinogen-induced mammary tumors by interfering with the postinitiation, promotion phase of carcinogenesis. We studied the effects of selenium on the growth of rat mammary tumor cells in primary culture. Our objective was to determine whether selenium had any direct influence on cell growth which might explain its influence on tumor development. Rat mammary tumors were induced by N nitrosomethylurea. Tumor epithelium was prepared by collagenase dispersion and the cells were separated by Ficoll gradient centrifugation. The tumor epithelium was grown in primary culture using a defined serum-free medium. The addition of low concentrations of sodium selenite, less than 1.0 micrograms/ml, stimulated tumor cell proliferation. Protein synthesis and the production of type IV collagen increased within the first hour of exposure, prior to any measurable increase in DNA synthesis. Concentrations of selenite greater than 1.0 micrograms/ml inhibited cell proliferation, the synthesis of protein, and the replication of DNA in a dose-related manner. These studies demonstrated that selenium has the potential to influence the postinitiation phase of rat mammary tumorigenesis by directly altering the growth of tumor cells, possibly through the regulation of protein synthesis. PMID- 4034532 TI - Stimulation of rat uterine collagen synthesis by relaxin. AB - Immature, ovariectomized, estrogen-primed rats respond to the administration of porcine relaxin by an increase in the incorporation of labeled amino acids ([14C]leucine, [14C]phenylalanine, [3H]proline) into uterine proteins in vitro. The maximum response occurs about 12 hr after a single injection of 0.1 mg relaxin in benzopurpurine 4B solution; subsequently, the relaxin effect declines but is still apparent after 24 hr. Smaller, but still significant increases in incorporation rates can be induced by relaxin in the absence of estrogen priming. Uterine collagen synthesis, as indicated by the incorporation of [3H]proline and its conversion to hydroxyproline, appears to be a primary target of the relaxin stimulus, since the effect of relaxin upon proline incorporation into uterine collagen is significantly greater than its effect upon labeling of noncollagen protein. PMID- 4034533 TI - Composition of glycosaminoglycans from aortas from deoxycorticosterone-induced hypertensive pigs. AB - Hypertension was induced in young male pigs by subcutaneous implantation of deoxycorticosterone acetate in a Silastic rubber carrier. Hemodynamic variables were periodically monitored. Six to eight weeks after implantation, the animals were necropsied and aortas were dissected. Glycosaminoglycans (GAG) were isolated from aortas from hypertensive pigs and from normotensive controls. Individual glycosaminoglycans in mixtures were fractionated and quantitated by chromatography on Dowex 1 Cl- column. No differences were noted in total glycosaminoglycan concentration between hypertensive and control animal aortas; the differences in individual GAG in aorta media-adventitia between the groups were not statistically significant. The relative proportions of heparan sulfate and dermatan sulfate in aorta intima were significantly greater (p less than 0.05) in hypertensive aortas than in normotensive intima. These two glycosaminoglycans increased in hypertensive animals at the expense of chondroitin 4-sulfate and hyaluronic acid. There was no difference in chondroitin 6-sulfate between the groups. A possible explanation of changes of glycosaminoglycans in hypertension because of altered lysosomal activity is suggested. PMID- 4034534 TI - Effect of thrombopoietin on in vitro production of megakaryocytes from fetal mouse liver cells. AB - Plasma clots containing fetal mouse liver cells (FMLC) were used to study the effects of a thrombocytopoiesis-stimulating factor (TSF) from kidney cell culture medium on the proliferation and maturation of megakarocytes. Cells in the megakaryocytic series were identified by the presence of acetylcholinesterase (AChE) and by their morphological and ultrastructural characteristics. For these experiments, 1 X 10(3) to 1 X 10(5) FMLC were cultured for 1-7 days with 0-5 micrograms of TSF; control cultures were treated with production medium (PMC) in which kidney cells had not been grown. The number of AChE+ cells that were observed depended upon the number of cells plated, i.e., after 6 days of culture with 5 micrograms of TSF, an average of 187 AChE+ cells was found after plating 1 X 10(4) cells and 1020 AChE+ cells were observed after plating 1 X 10(5) cells. In dose-response experiments, the number of AChE+ cells rose with increasing doses of TSF. Significantly elevated numbers of AChE+ cells were observed after the addition of 1-5 micrograms of TSF. The optimum time of culture, based upon the number of AChE+ cells found, was 3-5 days. Ultrastructural analysis of megakaryocytes in plasma clots showed evidence of platelet shedding on Day 5. After the culture of FMLC with TSF, a larger number of AChE+ cells was formed from a given number of cells plated than in previous studies that used adult bone marrow cells. Therefore, because of its greater sensitivity, FMLC may be useful for the assay of low levels of TSF, and may be a valuable tool for studying the effects of megakaryocytic regulatory factors on megakaryocytopoiesis. PMID- 4034535 TI - Antineoplastic activity of N-maleamide homocysteine thiolactone amide encapsulated within liposomes. AB - The antineoplastic activity of N-maleamide homocysteine thiolactone amide (MHTA) encapsulated within liposomes was studied in mice with transplanted tumors. Tumor weight was decreased by 4-5 biweekly intraperitoneal injections of MHTA in liposomes in DBA/2N females with MTG mammary adenocarcinoma (35% of control value, P less than 0.005) and in C57B1/6N males with MUO4 rhabdomyosarcoma (11% of control value, P less than 0.0000001). Tumor incidence was reduced from 84 to 63% (P less than 0.05) and from 100 to 32% (P less than 0.001) in the two systems, respectively. When the compound was administered in dimethyl sulfoxide to A/HeJ females with A10 mammary adenocarcinoma by daily intraperitoneal injection, tumor weight was reduced to 70% of control value (P less than 0.05), and there was no decrease in tumor incidence (100%). No toxicity was observed at the therapeutic dose utilized, 10 mg/kg/day. N-Maleamide homocysteine thiolactone amide is a derivative of the normal biochemical constituents, maleic acid and homocysteine thiolactone. The results show that the N-substituted maleamide derivative of homocysteine thiolactone decreases the growth of murine tumors of two different histological types, when administered encapsulated within liposomes. PMID- 4034536 TI - Arteriolar and systemic autoregulatory responses during the development of hypertension in the spontaneously hypertensive rat. AB - Pressure-flow curves were constructed to determine whether acute autoregulation in rat skeletal muscle was altered during the development of hypertension in the spontaneously hypertensive rat (SHR). Under chloralose:urethane anesthesia, hindlimb blood flow and pressure, plus diameter changes of gracilis muscle arterioles, were simultaneously measured in the 6- and 9-week Wistar-Kyoto (WKY) and SHR. Femoral blood flow was measured by electromagnetic flowmetry and hindlimb pressure controlled with an hydraulic occluder. Arteriolar diameters were measured using image shearing techniques. Acute autoregulatory capacity was assessed by comparing the closed-loop gain and the regression lines over the regulated and passive pressure ranges of the pressure-flow curves. The lower pressure limit of autoregulation (LPLAR) shifted upward as the blood pressure increased in the SHR with age; it did not shift in the WKY. Resting hindlimb flow, elevated in the SHR at 6 weeks, was also elevated at the LPLAR. At 9 weeks hindlimb blood flow was comparable in the WKY and SHR. As blood pressure was increased autoregulation was accompanied by vasoconstriction of gracilis arterioles. However, neither the gain of the autoregulatory system nor the regression lines describing the pressure-flow curves were different between the hypertensive and normotensive animals at either age. These results indicate that the acute autoregulatory response mechanism was not affected by the developing hypertension in the SHR, and is consistent with a structural basis for the chronic maintenance of the elevated peripheral vascular resistance. PMID- 4034537 TI - Cassava is not a goitrogen in mice. AB - To examine the effect of cassava on the thyroid function of mice, we fed fresh cassava root to mice and compared this diet with low iodine diet and Purina. Cassava provided a low iodine intake and increased urine thiocyanate excretion and serum thiocyanate levels. Mice on cassava lost weight. The thyroid glands of mice on cassava were not enlarged, even when normalized for body weight. The 4- and 24-hr thyroid uptakes of mice on cassava were similar to those of mice on low iodine diets. Protein-bound [125I]iodine at 24 hr was high in mice on either the cassava or low iodine diets. The thyroid iodide trap (T/M) was similar in mice on cassava and low iodine diets. When thiocyanate was added in vitro to the incubation medium, T/M was reduced in all groups of mice; under these conditions, thiocyanate caused a dose-related inhibition of T/M. The serum thyroxine (T4) and triiodothyronine (T3) concentrations of mice on cassava were reduced compared with mice on Purina diet. Thyroid T4 and T3 contents of mice on cassava were relatively low compared with mice on Purina diet. Hepatic T3 content and T4 5' monodeiodination in liver homogenates were reduced in mice on cassava compared with other groups. The data show that cassava does not cause goiter in mice. The thiocyanate formed from ingestation of cassava is insufficient to inhibit thyroid iodide transport or organification of iodide. The cassava diet leads to rapid turnover of hormonal iodine because it is a low iodine diet. It also impairs 5' monodeiodination of T4 which may be related to nutritional deficiency. These data in mice do not support the concept that cassava per se has goitrogenic action in man. PMID- 4034538 TI - The pH dependence of disobutamide-induced clear cytoplasmic vacuoles in cultured cells. AB - Cellular uptake of disobutamide (D), and clear cytoplasmic vacuoles (CCV) induction by D in cultured rat urinary bladder carcinoma cells were dependent on the culture medium pH. At pH 6.0-6.7, drug uptake was slow and no CCV formed in 24 hr. At pH 7.0-8.0, the rate of D uptake and early appearance of CCV were directly proportional to increased basicity. This was explained by the increasing fraction of un-ionized D molecules at increasing basicity of the culture medium. It is only these electrically neutral D molecules which can penetrate the lipoidal cell membrane to induce formation of CCV. Intracellular presence of D was demonstrated by mass spectrometry methods. The results indicate that D is incorporated intracellularly, that D and not its metabolite(s) is in cells, and suggest that CCV are a result of drug sequesteration. PMID- 4034539 TI - Effect of antilymphocyte serum and neonatal thymectomy upon onset of diabetes in the Chinese hamster. AB - Prediabetic Chinese hamsters were treated with antilymphocyte serum (ALS), or thymectomized in order to test the hypothesis that beta-cell loss leading to diabetes in this animal model was related to cell-mediated autoimmunity. In addition, passive transfer of diabetes from the Chinese hamster to the nude mouse was attempted by transplantation of lymphocytes. Treatment of prediabetic Chinese hamsters with ALS or thymectomy did not alter development or severity of diabetes in this animal model. Lymphocytes from newly diagnosed diabetic Chinese hamsters did not cause hyperglycemia in nude mice. These three lines of evidence suggest that cell-mediated autoimmunity does not contribute to the etiology of diabetes in the Chinese hamster. The Chinese hamster remains a good model for the study of those forms of diabetes not related to cell-mediated autoimmune phenomena. PMID- 4034540 TI - Intracellular protein catabolism. Proceedings of the Fifth International Symposium on Intracellular Protein Catabolism. May 29-June 2, 1984, Airlie, Virginia. PMID- 4034541 TI - Properties of human liver cathepsin L. PMID- 4034542 TI - A comparative study of cathepsins N and L and their distribution in different tissues. PMID- 4034543 TI - Proenkephalin and enkephalin metabolism by rat brain cathepsin B: conversion, inactivation, and suppression by an endogenous inhibitor. PMID- 4034545 TI - Leucine aminopeptidase activity is diminished in aged hog, beef, and human lens. PMID- 4034544 TI - Properties of a protein that is purified from bovine skeletal muscle that inhibits the Ca2+-dependent proteinase. PMID- 4034546 TI - Fragmentation of extracellular and intracellular polypeptides by free radicals. PMID- 4034547 TI - Relationship of the redox state to muscle protein degradation. AB - With increasing muscle size, incubated or fresh-frozen leg muscles showed a more reduced redox state and slower proteolysis. The ln of these data gave a linear correlation showing faster proteolysis under more oxidized conditions. In incubated diaphragms, the inhibitory effects of insulin and catecholamines on proteolysis were associated with a more reduced state. Fasting, trauma or cortisol treatment led to accelerated proteolysis and a more oxidized state. Long term fasting and refeeding supported this relationship, as did streptozotocin diabetes. Like the NAD+ and NADP+ redox couples, the glutathione couple seemed to fit this relationship. Use of proteinase inhibitors showed that the redox state probably mediated the effects of the various factors on proteolysis rather than vice versa. Muscle contains thioltransferase which catalyzes the formation of glutathione-protein mixed disulfides. We propose that increased formation of oxidized glutathione and its interaction with muscle proteins may act as a signal for the initiation of proteolysis. PMID- 4034548 TI - Regulation of catabolism of ribonuclease A microinjected into human fibroblasts. AB - We are using ribonuclease A (RNase A) as a model protein to study how the degradative rates of proteins are regulated within cells. RNase A and several derivatives can be microinjected into confluent cultures of human fibroblasts using red cell-mediated microinjection. The half-life of RNase A is 80-100 hrs in cells maintained in the presence of serum, and the degradative rate is enhanced approximately two-fold upon serum withdrawal. The ability of fibroblasts to regulate breakdown of this protein depends on a small peptide region within the amino terminal twenty amino acids. This amino terminal peptide from RNase A can be covalently attached to unrelated proteins and will cause their catabolism to become serum responsive. The mechanism of degradation of RNase A involves lysosomal pathways both in the presence and absence of serum, and the enhanced catabolism during serum deprivation results from a two-fold increase in the rate of uptake of the protein by lysosomes. These findings suggest that autophagy, or some other process occuring in serum-deprived cells, can be highly selective. PMID- 4034549 TI - Amino acid control of hepatic protein degradation: novel requirement for alanine. PMID- 4034550 TI - Pathways of intracellular sequestration and protein degradation in isolated rat hepatocytes. PMID- 4034551 TI - Microinjection of isolated lysosomes: a model for studying autophagic sequestration of cell organelles. PMID- 4034552 TI - Fate of exogenous proteins after internalization by endocytosis and microinjection in cultured myotubes. PMID- 4034553 TI - Degradation of microinjected ribonuclease A and ribonuclease S-protein by lysosomal pathways. PMID- 4034554 TI - Sequestration and hydrolysis of electroinjected [14C]lactose as a means of investigating autophagosome-lysosome fusion in isolated rat hepatocytes. PMID- 4034555 TI - Effect of serum deprivation and replacement on proteolysis in cultured human fibroblasts. PMID- 4034556 TI - Effects of denaturation and methylation on the degradation of proteins in cultured hepatoma cells and in reticulocyte cell-free systems. PMID- 4034557 TI - The stimulatory effect of glutathione on proteolysis in mouse kidney lysosome suspensions. PMID- 4034558 TI - Effect of protease inhibitors on short-term proteolysis in hepatocytes. PMID- 4034559 TI - Pyridoxal phosphate as a probe for the degradation products of skeletal muscle glycogen phosphorylase. PMID- 4034560 TI - Aortic perfusion pressure affects cardiac protein turnover. PMID- 4034561 TI - Intracellular degradation of newly synthesized collagen. PMID- 4034562 TI - Ascites hepatoma: a model system to investigate cell protein degradation in the animal as well as in vitro. PMID- 4034563 TI - Liver and skeletal muscle protein metabolism in Yoshida ascites hepatoma AH-130 bearing rats. PMID- 4034564 TI - Changes in urinary 3-methylhistidine/creatinine ratio in human subjects after strenuous exercise. PMID- 4034565 TI - Cathepsin L--a lysosomal cysteine proteinase. PMID- 4034566 TI - Relationships between protein degradation and glucose metabolism in skeletal muscle. PMID- 4034567 TI - Protein degradation and lysosomal proteinases in cultured fetal rabbit cardiac myocytes. PMID- 4034568 TI - Proteinase activities in normal and dystrophic chicken myoblasts in culture. PMID- 4034569 TI - Protein turnover in the rat uterus during and after pregnancy. PMID- 4034570 TI - Replacement perfusion of cultured eucaryotic cells: a method for the accurate measurement of the rates of growth, protein synthesis and protein turnover. PMID- 4034571 TI - Degradation of abnormal protein in rabbit reticulocytes: detection of intermediates. PMID- 4034572 TI - Inhibition of protein degradation and of cellular autophagy in growing as compared to density inhibited fibroblasts. PMID- 4034573 TI - Enhanced intracellular procollagen degradation in skins of streptozotocin-induced diabetic rats: a causal relationship to underhydroxylation. PMID- 4034574 TI - Infection, immunity, and blood transfusion. Proceedings of the XVIth Annual Scientific Symposium of the American Red Cross. Washington, DC, May 9-11, 1984. PMID- 4034575 TI - Rationale for suppression of adrenal steroidogenesis in advanced prostatic cancer. PMID- 4034576 TI - Ketoconazole an inhibitor of the cytochrome P-450 dependent testosterone biosynthesis. PMID- 4034577 TI - Human prostate cancer (PC-82) in nude mice: a model to study androgen regulated tumor growth. PMID- 4034578 TI - Clinical applications of ketoconazole in prostatic cancer. PMID- 4034579 TI - Orchidectomy and oestrogens as secondary forms of treatment for metastatic prostatic cancer. AB - When in a patient with metastatic prostatic cancer progression of tumour growth occurs during first-line endocrine therapy the prognosis appears to be poor. In the literature there are only a few reports about the efficacy of second-line treatment with castration or oestrogens indicating a mean response rate of 15 20%. The most effective sequence of endocrine therapy has not been determined. Therefore we have evaluated the data of 932 patients treated for prostatic cancer between 1970-1980 in our hospital. Of these 932 patients 516 (55%) had metastatic disease. In 275 patients (53% of the patients with metastatic disease) the metastases were already detected at time of diagnosis of the primary tumour. Adjuvant therapy appeared to cause a delay in the occurrence of overt metastases but (nearly) not an improvement of overall survival for patients who developed metastases. We found no relationship between survival from the time of presentation of metastases and age. The median survival after occurrence of metastases was 18 months with a 5-year survival of 10%. From start of second-line therapy the median survival appeared to be only 6 months with a death rate of 3 times as high as from start of first-line therapy. Looking into our data one could be tempted to express that 1) the combination of castration plus oestrogens as a first-line therapy seems to have a somewhat better effect on survival than other forms of endocrine therapy; 2) that as a second-line therapy castration appeared a suitable form of treatment after oestrogens, antiandrogens after castration and oestrogens when antiandrogens were used in the first line. PMID- 4034580 TI - Androgen depletion/repletion in combination with chemotherapy: strategy for secondary treatment of metastatic prostatic cancer. PMID- 4034581 TI - New principles in the management of metastatic prostatic cancer. PMID- 4034582 TI - Combination of hormonal and cytostatic treatment for advanced carcinoma of the prostate. PMID- 4034584 TI - EORTC Genitourinary Group Monograph 2, Part B. Superficial bladder tumors. Proceedings of a symposium held in York, England, November 16 and 17, 1984. PMID- 4034583 TI - Pharmacology and clinical studies with RU 23908 (Anandron). PMID- 4034585 TI - Methotrexate in superficial bladder cancer--what happens to the drug? PMID- 4034586 TI - Superficial bladder cancer--problems with selection. PMID- 4034587 TI - Intravesical and intradermal BCG-RIVM application: a toxicity study. PMID- 4034588 TI - The analysis of results in prophylactic superficial bladder cancer studies. PMID- 4034589 TI - The need for long-term follow-up studies after treatment of superficial bladder cancer (Tis/Ta/T1), especially after intravesical chemotherapy. PMID- 4034590 TI - The costs of intravesical chemotherapy. PMID- 4034591 TI - Intravesical chemoprophylaxis of superficial transitional cell carcinoma of the bladder. When should the drug be given? PMID- 4034592 TI - Carcinoma of the large bowel and its precursors. Proceedings of a conference. Detroit, September 27-28, 1984. PMID- 4034593 TI - Growth rates of benign and malignant neoplasms of the colon. AB - In summary, there is a wide, natural variance in rates of growth of benign and malignant neoplasms of the lower bowel. There is a crude correlation between growth rate and histopathology. The difference between DT(act) and DT(pot) is manifold. Primary surface desquamating cancers probably grow much slower than their metastases. These factors are of importance in understanding neoplastic behavior and in designing detection and treatment protocols. The gap in knowledge is for in vivo growth rates and mathematical patterns of growth in the period before a neoplasm reaches the threshold size permitting observation. The rates of growth are very relevant to screening and diagnostic strategies. PMID- 4034594 TI - Colonoscopy: its application and merit. AB - Much has been learned through the development of colonoscopy. This in turn has stimulated interest in roentgenographic studies and has provided a tool for conducting research studies that would not be possible without the ability to obtain tissue sequentially over a period of time. Despite these advances, questions still outnumber answers. As new technologies open doors for research that was not historically possible, commitment to research in endoscopy becomes increasingly important. The opportunities, importance and need for commitment to endoscopic research has recently been emphasized (Silverstein 1984). It is hoped that important research questions in endoscopy will be effectively addressed and this, in turn, will improve our knowledge about cancer of the large bowel and its precursors. PMID- 4034595 TI - The air contrast barium enema--indications and validity. AB - The double-contrast barium enema is a highly accurate and readily available procedure which is capable of diagnosing benign and malignant disease of the colon at an early state. The level of accuracy is a function of the radiologist's knowledge and willingness to assume complete responsibility for the patient. While reasonable results may be obtained with the high-kilovoltage single contrast method, it is our opinion that the double contrast examination is the more sensitive procedure and therefore the technique of choice. The double contrast examination ideally compliments the colonoscope and offers an alternative method for initial survey procedures or low cost follow-up examinations. PMID- 4034596 TI - Endoscopic laser surgery. PMID- 4034598 TI - A multistage model for human colon carcinoma development from tissue culture studies. PMID- 4034597 TI - Animal model for colorectal cancer. AB - The development of a satisfactory rodent model for cancer of the large intestine began with the discovery by Laqueur and associates in 1962 that the plant product, cycasin (methylazoxymethanol glycoside), is a potent carcinogen for rodents. Soon after that, DMH, AOM, and MAM were found to be even more efficient intestinal carcinogens in rats. These three compounds, plus two direct acting carcinogens (MNNG, MNU) are used almost exclusively in current animal investigations. Although all these chemicals have some degree of activity in all rodents, they are most effective in rats. Various rat strains differ somewhat in susceptibility, Sprague-Dawley being the most sensitive to these carcinogens. Cancers of the large intestine in the animal model resemble adenocarcinomas in humans, and they spread in a similar manner except that metastases to the liver and lung are very uncommon in animals. Animal studies support epidemiological and human experimental observations of dietary factors involved in colorectal cancer formation. Most physicians believe that the majority of colorectal cancers develop from preexisting adenomas. Morson has shown that large adenomas and villous adenomas have a greater risk of developing cancer than small adenomas. Hill has theorized that there are different factors responsible for the formation of small adenomas from normal mucosa, for the growth of small to large adenomas, and for the development of cancer from large adenomas. Animal studies provide some support for this concept. Weak intestinal carcinogens tend to induce more benign adenomas than carcinomas. Very small doses of strong carcinogens also induce some adenomas and a few early polypoid intestinal cancers after a long latent period. Moderate to large amounts of DHM, for example, induce only malignant lesions even when these lesions are as small as 1 mm. These observations suggest a relationship between adenomas and carcinomas. There is also biochemical evidence to support the staged progression of carcinogenesis. An example is the graded increases in ODC activity that occur in tissues undergoing tumorigenesis. PMID- 4034599 TI - Cell kinetic approaches to defining premalignant conditions. PMID- 4034600 TI - Comparative histogenesis and pathology of naturally-occurring human and experimentally induced large bowel cancer in the rat. PMID- 4034601 TI - The mode of formation and progression of chemically induced colonic carcinoma. PMID- 4034602 TI - Premalignant lesions of the colorectum. PMID- 4034603 TI - The carrageenan model for experimental ulcerative colitis. PMID- 4034604 TI - Biochemical approaches to the intervention of large bowel cancer. PMID- 4034605 TI - Hemoquant--an approach to screening for fecal occult blood. PMID- 4034606 TI - Vegetable peroxidase inhibitor--an improvement in the guaiac fecal occult blood test. PMID- 4034607 TI - Screening for colorectal cancer: the rationale and a recent advance in the detection of fecal occult blood. AB - For the very first time, an occult blood test has been designed to conform to convenient and natural bathroom habits. For the very first time, we therefore expect the general public to agree willingly to participate in occult blood testing. For the very first time, we expect Early Detector to successfully screen the general public, so that survival rates from colon and rectal cancer may show a significant improvement in the next decade. PMID- 4034608 TI - Cancer and dysplasia in ulcerative colitis: an insoluble problem? PMID- 4034609 TI - Colorectal cancer in Crohn's colitis and other large intestinal diseases: is there a dysplasia-carcinoma sequence? PMID- 4034610 TI - Effect of additives on the photostability of chloramphenicol in Clark Lubs borate buffer at pH 7.8. PMID- 4034611 TI - The permeation behavior of several membranes with potential use in the design of transdermal devices. PMID- 4034612 TI - Effect of the nature of the oil and electrolyte concentration on the type and stability of emulsions. PMID- 4034613 TI - [The effect of excipients on the rate of liberation of two non-steroidal anti inflammatory agents from gels]. PMID- 4034614 TI - [Sweet balm--still capable of surprises]. PMID- 4034615 TI - Scopolamine degrades spatial working memory but spares spatial reference memory: dissimilarity of anticholinergic effect and restriction of distal visual cues. AB - The influence of the centrally active anticholinergic, scopolamine hydrobromide, on working and reference memory was studied in rats tested in a 12-arm radial maze. Both 0.25 and 0.5 mg/kg doses of the drug increased the number of working memory (WM) errors but had no effect on reference memory (RM) errors. A lower dose (0.125 mg/kg) was ineffective, as was the peripherally active anticholinergic, scopolamine methylbromide (0.5 mg/kg). Some of the behavioral effects of anticholinergics on spatial memory are mimicked by blindness or eliminating distal visual cues. If distal visual cues were more important for maintaining accurate WM than for RM, the selective effect of scopolamine on WM could be easily explained. But surrounding the maze with a curtain to eliminate extramaze cues increased RM errors without significantly increasing WM errors. Thus, the selective effect of anticholinergies on spatial memory in the radial maze is qualitatively different from the effect of restricting distal visual cues and must arise from some other action of the drug. PMID- 4034616 TI - The role of trazodone metabolism in its inhibitory action on avoidance response. AB - To assess the role of trazodone metabolism in its depressant action on conditioned avoidance response we investigated whether in the mouse brain 3 chlorophenylpiperazine (CPP) is formed from trazodone, whether trazodone metabolism is affected by a drug metabolism inhibitor, proadifen, and how trazodone, CPP and their combinations act on avoidance responses in proadifen pretreated mice. It was found that CPP is formed from trazodone in mice, that proadifen inhibits trazodone metabolism, and that the moderate and transient inhibitory effect of trazodone on avoidance responses is dramatically potentiated and prolonged in proadifen-pretreated mice. This effect, and inhibition of unconditioned escape response observed in mice receiving lower doses of trazodone after proadifen pretreatment, were counteracted by CPP. The results indicate that the inhibitory action of trazodone on avoidance response is caused by the parent compound, and that it is brief and moderate because of the rapid metabolism of the drug with formation of CPP which counteracts the depressant effect of the parent compound. PMID- 4034617 TI - Erythrocyte differentiation of naturally occurring isotopic lithium abundances. AB - Lithium is effective in the treatment of mania. There are two naturally occurring stable lithium isotopes, Li-7 (92.6%) and Li-6 (7.4%). Usually there is little differentiation between isotopes of an element, but chemical and behavioural data suggest dissimilarities exist between lithium isotopes. Results are now reported indicating that a group of manic patients given lithium chloride were able to differentiate Li-6 from Li-7 at the membrane level. Blood samples were drawn, erythrocytes separated from plasma and the isotopic abundances of Li-6 and Li-7 determined by atomic absorption spectrophotometry. The ratio of abundances of Li 6 in the erythrocyte and plasma was 1.274 indicating the erythrocyte membrane had the in vivo capability of isotope fractionation. PMID- 4034618 TI - Effect of decapitation and stress on some plasma electrolyte levels in rats. AB - Male Sprague-Dawley rats carrying indwelling jugular catheters were used to compare two methods of blood collection, catheterization or decapitation, for obtaining the plasma levels of several electrolytes. Decapitation resulted in higher levels of Ca2+, Mg2+, and K+ (18%, 23%, and 35% respectively) compared to catheter values. In a second experiment, catheterized rats were used to examine the effect of immobilization and footshock on plasma electrolytes. Both forms of stress elevated Mg2+, whereas only immobilization elevated Ca2+. Post-stress K+ levels were significantly different than control values. These experiments demonstrate that catheterization must be used to obtain true plasma electrolyte levels, and that electrolytes may be selectively altered depending on the nature of the stressor. PMID- 4034619 TI - Disregulation of hypothalamic-pituitary-adrenal axis in the mentally retarded. AB - Previous reports of cognitive and social improvement in the mentally retarded after administration of MSH/ACTH fragments suggested disregulation of the hypothalamic-pituitary-adrenal (HPA) axis. The current study examined the integrity of this system with the Dexamethasone Suppression Test (DST). The DST is a biological index of HPA integrity and recently has been used as a diagnostic aid for endogenous depression. Thirty-five mentally retarded patients were administered 1 mg of dexamethasone just after a sample of blood was taken. Blood samples were analyzed for cortisol by RIA at 11:00 p.m. (basal), 8:00 a.m., 4:00 p.m., and 10:00 p.m. Between 40% and 48% (depending on sampling) of the patients failed to suppress cortisol (greater than 4 micrograms/dl), after the DST challenge. The results suggested that a significant proportion of mentally retarded patients have a DST index reflecting a disordered HPA axis and complements earlier studies of cognitive enhancement observed after treatment with MSH/ACTH fragments. The possibility that the stress of hospitalization was related to a disordered HPA was suggested. The possible co-existence of depression in the mentally retarded invites further study. PMID- 4034620 TI - Reproductive physiology and behavior in the male rat following acute and chronic peripheral adrenergic depletion by guanethidine. AB - The effect of guanethidine, an adrenergic neuron blocking agent, on sexual behavior, penile reflexes, and spontaneous seminal emission (SSE) in the rat was studied by acute (i.e., 4 hours prior to testing) and daily IP injection of a low (5 mg/kg) and moderately high (25 mg/kg) dose of the drug. Acute low dose treatment eliminated the expulsion of a seminal plug with behavioral ejaculation without affecting sexual behavior; while acute high dose administration significantly decreased the number of intromissions preceding ejaculation and eliminated emission in copula and SSE for 3 days, with no evidence of retrograde ejaculation. Acute high dose treatment also increased the number of long flips displayed in the penile reflex test, and resulted in significant depression in plasma testosterone (T) and luteinizing hormone (LH) levels. Daily injection with the low dose eliminated emission in and ex copula for 4 weeks, without altering sexual behavior or penile reflexes. Seminal emission in copula reappeared more rapidly after stopping injections than SSE. Chronic high dose treatment was also without effect on copulatory activity. There was a partial recovery of emission in copula by the fourth week of treatment, suggesting that a nonadrenergic mechanism had assumed this function. In penile reflex tests conducted after 4 and 8 weeks, significantly fewer erections were displayed by drug-treated animals. During the period of initial recovery of emission in copula, emission during the reflex test was markedly increased, but SSE was decreased. Plasma T was significantly suppressed after two and four weeks of daily injections, but not thereafter, while plasma LH levels were not affected by the drug. PMID- 4034621 TI - Effect of dopamine agonists and fenfluramine on discriminative behavior in obese and lean Zucker rats. AB - Dopamine agonists and fenfluramine were used as pharmacological probes to investigate the possible difference in sensitivity and time course of drug action in genetically obese Zucker rats and their lean littermates. All rats were trained to discriminate between the stimulus properties of 0.6 mg/kg d amphetamine and its vehicle in a two-lever, food-motivated operant task. Once trained, both groups of rats showed a dose-related decrease in discriminative performance with lower amphetamine doses. Analysis of the dose-response curves indicated an ED50 for the obese rats of 0.17 mg/kg and for the lean group of 0.14 mg/kg. Administration of 0.3-1.2 mg/kg l-amphetamine and 2.5-10.0 mg/kg cocaine produced a pattern of responding similar to that observed with d-amphetamine. In contrast, 0.08-mg/kg apomorphine produced saline-appropriate responding and 1.5 2.5 mg/kg fenfluramine produced intermediate results in both groups. Time-course experiments indicated that the lean rats maintain errorless discriminative performance through 90 min post-injection, whereas the obese rats discriminate d amphetamine significantly less at that post-administration time. The results suggest a similar sensitivity to d-amphetamine and other dopaminergic agonists in obese and lean rats with a difference in the time-course of d-amphetamine's action between these two groups. PMID- 4034622 TI - Rate-dependency and hyperactivity: methylphenidate effects on operant responding. AB - The two most common treatment for hyperactivity are psychopharmacological regimens and behavior therapy. Although the concurrent use of stimulant medication has been purported to enhance a child's rate of responding under a behavior management program, studies examining the interaction of the two treatments have been unable to confirm this hypothesis. The present investigation sought to examine the effects of differing levels of methylphenidate hydrochloride (Ritalin) upon operant responding with hyperactive children. After an initial drug-free training period, 10 first through fourth grade hyperactive males performed an operant key-pressing task under a mult VR 5 FI 30 sec reinforcement schedule across four randomly determined, double-blind drug conditions (placebo, 5, 10, 15 mg). Only VR responding changed significantly during medication conditions; however, rate-dependent psychostimulant effects were found within both reinforcement schedules. Discrepancies with animal rate dependency and implications for treatment and future research are discussed. Medication effects on operant responding appear to depend upon the reinforcement schedule and dose employed. PMID- 4034623 TI - Genetic differences in daily rhythms of pain sensitivity in mice. AB - A dark phase increase in pain sensitivity was evident in C57BL/6 inbred mice. On the contrary Swiss mice are characterized by decreased nocturnal pain sensitivity. The latter finding is in agreement with a number of previous studies based on albino mice. However, our findings indicate that (1) nocturnal decreased pain sensitivity is not the rule in the mouse and (2) large differences are evident when the onset in peak nocturnal analgesia is considered. PMID- 4034624 TI - Suppressant effect of REM sleep deprivation on neophobia in normal rats and in rats with selective DSP-4 induced damage of locus coeruleus neurons. AB - The influence of REM sleep deprivation (REMD) on open field behavior of normal and locus coeruleus (LC)-damaged animals was investigated under the assumption that REMD suppresses neophobia in rats. REMD (for 24 or 72 hr, water tank technique) produced marked changes in behavior of rats encountering a novel object (white cube) in the center of the open field. REMD induced an increase in activity of treated rats; latency to the object approach was shorter, the number of center entries, time spent in object exploration, frequency of ambulation and rearing were significantly higher than in controls, also defecation was nearly abolished. LC-damage (using DSP-4, a selective central noradrenergic neurotoxin) induced neophobic-like reactions manifested by significantly prolonged latency, tendency to decreased object exploration, center entries and reduction of ambulation and rearing. This "neophobic" behavior of DSP-4 rats was counteracted by REMD as well as by subchronic, but not acute treatment, with antidepressant oxaprotiline (2 X daily for 8 days, 10 mg/kg, IP). The results provide strong support for antineophobic activity of REMD. In addition, they indicate possible similarity of REMD and subchronic oxaprotiline action on neophobia-like behavior in rats with damaged LC-neurons. PMID- 4034625 TI - Failure of chronic haloperidol to affect prolactin secretion due to acute haloperidol administration. AB - Withdrawal from chronic haloperidol exposure was associated to unaltered circulating levels of prolactin (PRL), decreased 3H-spiperone binding sites in the anterior pituitary and increased 3H-spiperone binding sites in the striatum of male rats. Haloperidol (0.1 mg/kg ip) induced similar rises in plasma PRL in haloperidol-or saline-treated rats and the dose of 0.01 mg/kg was ineffective in both groups. These findings illustrate the poor relatedness existing at the pituitary D2 receptor between biochemical and functional indices. PMID- 4034626 TI - Tissue distribution, urinary, fecal and biliary excretion of 14C bendazac L lysine salt in rats. AB - The distribution of bendazac in the plasma and some rat tissues was studied after single oral administration of 14C bendazac L-lysine salt. The drug is distributed in varying amounts in the liver, kidneys, spleen, muscle, plasma and lens. In these tissues, the drug kinetics is similar, except for the lens where elimination of the drug is slower. More than 80% of the radioactivity administered is excreted through the urine and feces. Fecal excretion is due to the high biliary excretion. PMID- 4034627 TI - The effects of zinc sulphate on hypercholesterolaemia induced by cholesterol choleate in rats. AB - The effects of zinc sulphate on cholesterol-choleate-induced hypercholesterolaemia were studied in rats. Zinc sulphate (20 or 40 mg/kg, p.o. once daily for 5 days) administration, which raised serum zinc levels, significantly increased bile acid secretion and lowered high-density lipoprotein cholesterol (HDL-C) levels in the serum. Cholesterol-choleate, given by the same route and schedule, markedly elevated serum total cholesterol level, but decreased serum HDL-C concentration. Bile acid in serum and in bile was also increased, but these changes were inhibited by zinc sulphate pretreatment. Zinc sulphate also worsened the decrease in HDL-C and slightly prolonged the elevation in total cholesterol produced by cholesterol-choleate administration. It is concluded that the moderate increase in serum total cholesterol level by zinc sulphate could be due to inhibition of hepatic metabolism of cholesterol to bile acid. The specific action of zinc ions on HDL-C metabolism is discussed. PMID- 4034628 TI - The transition from a fixed ratio to a fixed interval schedule of reinforcement in hypo and hyperthyroid rats. AB - The modification of behavior caused by hypo and hyperthyroidism were studied when the schedule of reinforcement was changed from a fixed ratio to a fixed interval. The conditions of hypo and hyperthyroidism were obtained with a chronic administration of methimazole and of 1-thyroxine. The level of the modifications of thyroid activity was determined by evaluation of the basal metabolic rate and of the plasma levels of T4. Hyperthyroidism caused no modification of the rat behaviour. A difficulty in adapting to the new experimental situation (learning) was found in hypothyroidism. This effect is evident in high hypothyroidism. In low hypothyroidism a depression of the rat behaviour may interfere with the modification of the learning process. PMID- 4034629 TI - Increased erythrocyte glutathione peroxidase activity in psoriatics consuming high-selenium drinking water at the Dead-Sea Psoriasis Treatment Center. AB - Erythrocyte selenium-dependent glutathione peroxidase activity was measured in psoriatic Danes, before and after their four-week balneological therapy at the Ein-Bokek International Psoriasis Treatment Center, on the Dead-Sea shore in Israel. The drinking water in Ein-Bokek was found to be rich in selenium, a trace element with anticarcinogenic properties and of great importance in human nutrition and health. The most reliable biological parameter for increase in selenium bioavailability is the erythrocytes' glutathione-peroxidase activity. As psoriasis is a proliferative skin disease, the activity of this enzyme was assayed in 35 psoriatic Danes and in 25 long-term local hotel workers, as well as in 34 volunteers drinking low-selenium water. The glutathione peroxidase activity in the psoriatic patients increased significantly during their four-week stay in Ein-Bokek. Erythrocyte glutathione peroxidase activity in the hotel workers was 50% higher than that in the healthy volunteers consuming low-selenium water. A possible role of selenium in psoriasis is suggested. PMID- 4034631 TI - [Is there interaction between biotransformation products and sunlight?]. PMID- 4034630 TI - In vitro interaction of organic mercury compounds with soluble glutathione S transferases from rat liver. AB - The in vitro interaction of organic mercury compounds with rat liver glutathione S-transferases (GST) was studied, using reduced glutathione (GSH) and 1-chloro 2,4-dinitrobenzene (CDNB) as substrates. The inhibition of the GST activity was dose dependent, but not linear. The different GST isoenzymes were inhibited to different degrees. Kinetic studies never revealed competitive inhibition, with CDNB or with GSH as the variable substrate. Titration of remaining GSH in appropriate incubation mixtures with organomercurials revealed no GST catalyzed conjugation of these compounds with GSH. These experiments showed a spontaneous conjugation of the mercury compounds with GSH, explaining the parabolic inhibition observed in the kinetic studies with GSH as the variable substrate. Both organic and inorganic mercury are spontaneously conjugated with GSH, but interact with GST by direct binding to these proteins. This binding could have a protective function against mercury. No qualitative differences between organic and inorganic mercury were detected. PMID- 4034632 TI - [Selected procedures for the manufacture of containers for the production of drugs containing volatile elements. 90. Problems in the filling of plastic drug containers with fluid drug preparations]. PMID- 4034633 TI - [Synthesis of N-alpha-benzyloxycarbonyl-4-amidinophenylalanine amides as thrombin inhibitors]. AB - Based on 4-cyanophenylalanine, the title compounds had been obtained by benzyloxycarbonylation of the amino group, subsequent formation of the activated ester by 4-nitrophenol, its aminolysis and at least change of the cyano function to the amidine function via thiocarbamides and thioimid acid esters. The inhibitor effect against thrombin of the pyrrolidid 16 is analogous to those of the adequate N alpha-tosyl compound. PMID- 4034634 TI - 5-(2-Oxo-3-indolinylidene)thiazolidine-2,4-dione-1,3-di-Mannich base derivatives: synthesis and evaluation for antileukemic activity. AB - A novel series of 5-(2-oxo-3-indolinylidene)thiazolidine-2,4-dione, having the 1- and 3-positions of the isatin and thiazolidine rings respectively, substituted by various Mannich bases, was prepared. Five compounds were evaluated for antileukemic activity against P388 lymphocytic leukemia in the mouse. The di Mannich base with a dimethylamino component exhibited the highest activity of the tested compounds. Introduction of bromine into the aromatic moiety of isatin ring (position 5) increased the activity of the parent molecule to a smaller extent. PMID- 4034635 TI - [The purity testing of drugs and drug preparations according to flexible pharmacopoeia instructions]. AB - It is well known, that the quality standards of the various pharmacopoeias are based on certain procedures of synthesis or preparation concerning the drugs. Altering the manufacturing methods or importing these drugs from different producers, it may arise that the examined substance will formally come up to the quality directions of the pharmacopoeia agreed upon, but will contain possible, critical contaminations which are beyond the pharmacopoeia directions of examinations. PMID- 4034636 TI - [The structure of degradation products of neostigmine bromide]. AB - In aqueous temperature-stressed solutions of neostigmine bromide besides the known product of hydrolysis additional degradation products were discovered, detected by TLC and HPLC. By means of spectroscopic studies (1H-NMR, IR, UV, MS) and elemental analysis the isolated decomposition products were identified as 3 hydroxyphenyltrimethylammonium bromide (2), 3-dimethylaminophenol (3), 3 dimethylaminophenyl-dimethylcarbamate (4), 3-methylaminophenyl-dimethylcarbamate (5), 3-aminophenyl-dimethylcarbamate (6) and 4 (resp. 6)-bromo-3 dimethylaminophenyl-dimethylcarbamate (7). The structures of 2-7 were confirmed by comparison with synthesized authentic compounds. PMID- 4034637 TI - [Photochemical reactivity of methaqualone-1-oxide]. AB - The photoreactivity of methaqualone-1-oxide a main metabolite of the hypnotic methaqualone has been studied in polar and apolar solvents using UV- and daylight. Five photoproducts were isolated and identified by their analytical behaviour (TLC, UV, IR, high-resolution MS). The structure of the compounds 4, 6, 7, and 8 refer to unstable, reactive intermediates (oxaziridine, biradical) during the photolysis. PMID- 4034638 TI - [Determination of aminophylline and promethazine in suppositories]. AB - A method for the determination of theophylline and promethazine in suppositories is proposed which allows the determination of both components in a single suppositorium. The ingredients were extracted by hot water and addition of a little bit of sulfuric acid. Theophylline is determined potentiometrically without separation of promethazine by titrating the acid which is set free after addition of silver nitrate. Promethazine is separated by ether in alkaline medium, reextracted in HCl (0,1 mol/l) and determined colorimetrically. The precision of both methods is good. The results of the determination in the suppositories are given. PMID- 4034639 TI - [Dissolution processes and surface alteration. 4. Determination of the "effective" surface]. AB - A method is described for measuring the "effective" surface of a drug by means of dissolution parameters using the Paddle-model or a resorption-model respectively. The obtained values were compared with the specific surface which was determined by BET-technique. The "effective" surfaces obtained by means of the dissolution parameters are smaller than those determined BET-technique. PMID- 4034640 TI - Spectrophotometric and fluorimetric assay of prazosin hydrochloride in tablet form. PMID- 4034641 TI - [Determination of the limiting value of various analgesics in the blood and urine by means of thin layer chromatography using adsorbent resin Y29]. PMID- 4034642 TI - [A modified gas chromatographic method for the determination of propranolol in blood plasma]. PMID- 4034643 TI - [Molecular cavity filling and tabletting with beta-cyclodextrin]. PMID- 4034644 TI - [The enhancement of solubility of problem drugs. 5. Solubility of griseofulvin methylcellulose-PEG coprecipitates]. PMID- 4034645 TI - [The enhancement of solubility of problem drugs. 6. Antimycotic effectiveness of various griseofulvin preparations on Trichophyton mentagrophytes]. PMID- 4034646 TI - [The effect of propranolol on the pentetrazole-induced spindle activity in the EEG of the rat]. PMID- 4034647 TI - [The micelle catalysis of cetyltrimethyl ammonium bromide on phenylalanine arylation by 2,4-dinitrofluorobenzene]. AB - The reaction of phenylalanine with 2,4-dinitrofluorobenzene is increased by substances forming micells. As against the basic test, the increase is not dependent on conditions using solutions of 2.42 X 10(-3) mol phenylalanine and 1.62 X 10(-4) mol dinitrofluorobenzene the rate constant of the reaction proportionally increases by addition of 6.2 X 10(-4) to 4.4 X 10(-3) mol cetyltrimethyl ammonium bromide solution, then remains constant and finally decreases with further increase of the concentration. These curves could continuously be registered with varying pH values, although the basic and the catalytic reaction rate of both the reactions will increase according to the pH value with any buffer. A further increase of the basic and the catalyzed reactions can be enabled by increasing the temperature. The validity of the Arrhenius equation could be proved. PMID- 4034648 TI - [Preparation of soluble drug bead polymerisates as the basis of epoxide resins]. AB - It is reported about the embedding of good water soluble drugs in epoxides and it is demonstrated, that the selection of the tempers influences the liberation of drugs from the bead polymers. PMID- 4034649 TI - Suppositories containing cyclodextrin complexes. Part 2: Dissolution and absorption studies. AB - The dissolution and absorption of poorly water-soluble drugs from rectal suppositories can be enhanced by complexing these substances (e.g., essential oils, indomethacin) with beta-cyclodextrin. Preliminary in vivo studies showed, that the application of cyclodextrin complexes to suppositories, the same as to oral applications, resulted in an increased blood level. PMID- 4034650 TI - [Improvement of the solubility of problem drugs. 1. Production of iomeglamic acid fused and solidified products]. AB - The insoluble X-ray diagnostic iomeglamic acid could be converted to a more soluble modification by melting and solidifying it in liquid nitrogen. The amorphous state is proved by X-ray diffraction and differential thermal analysis. During storage, recristallisation of the product appears. By means of the proved amorphous state, it seems possible to determine the amount of the amorphous state, which makes the drug more soluble from solid dispersions. PMID- 4034651 TI - Pharmacokinetics of ethimizol in man. AB - The pharmacokinetics of ethimizol were studied in healthy volunteers given 1 mg/kg i.v. or 2 mg/kg orally. The serum concentrations of ethimizol were determined by HPLC. After i.v. infusion the kinetics of ethimizol could be described by a one-compartment model in 4 and by a two-compartment model in 1 subject. The elimination half-lives ranged from 34.1 to 79.2 min and the apparent volumes of distribution from 0.4 to 1.3 l/kg. After oral administration, the absorption half-lives ranged from 7.3 to 57.1 min. The absolute bioavailability varied between 3.6 and 22.2%. The binding of ethimizol to plasma proteins was less than 10%. PMID- 4034652 TI - Determination of some cardiac drugs using an ionselective chloride electrode and a silver electrode. AB - To determine hydrochlorides of butobendin, carbocromen, hexobendin, lidocaine, procainamide, todrazoline in pharmaceutical preparations, two analytical techniques were applied: the direct potentiometric method (from a standard curve) using an ion-selective chloride electrode and the method of potentiometric titration using a silver electrode as well as an ion-selective chloride electrode (indirect method). A statistical analysis has been carried out, and statistical tests were applied to compare the methods used. PMID- 4034653 TI - [Bioavailability of 2 piracetam preparations]. PMID- 4034654 TI - [Drug permeation through synthetic lipoid membranes. 18. The mechanism of ion pair permeation proton countertransport]. PMID- 4034655 TI - [The effect of water structure on the hydrogelling of polymethylmethacrylates. The ice theory of hydrogels]. PMID- 4034656 TI - Beta-casomorphin affects fast and slow action potentials in ventricular myocardium. PMID- 4034658 TI - Living, learning, and loopholes. PMID- 4034657 TI - [The anticonvulsant effect of propranolol in maximal electroshock in sub chronic applications]. PMID- 4034659 TI - "First-come first-served": analysis of an allocation principle. PMID- 4034660 TI - A physician's opportunity to contribute in the arts. PMID- 4034661 TI - No-fault compensation for human subjects injured in biomedical research: a public policy conflict. PMID- 4034663 TI - Patients: character-building teachers. PMID- 4034662 TI - Social censorship of medical and ethical decisions. PMID- 4034664 TI - Past and present. PMID- 4034665 TI - A woman doctor in Victorian fiction. PMID- 4034666 TI - Lower extremity weight bearing under various standing conditions in independently ambulatory patients with hemiparesis. AB - The purpose of this investigation was to determine if differences exist in weight bearing through the paretic and nonparetic lower extremities during various bilateral standing conditions. We used digital scales to measure weight bearing among 25 hemiparetic patients as they stood comfortably, as they alternately shifted as much weight as possible to each lower extremity, and as they alternately stood with each foot on a step. Patients bore significantly more weight (p less than .001) on their nonparetic than on their paretic lower limb during comfortable standing. They bore significantly more weight on their nonparetic extremity when shifting as much weight as possible to it than they did on their paretic extremity when shifting as much weight as possible to it (p less than .001). They bore significantly more weight (p less than .001) on the lower extremity that was not on the step during step standing. For patients comparable to those tested, standing with one lower limb on a 17-cm step should facilitate weight bearing through the contralateral lower limb. PMID- 4034667 TI - Effects of mental practice on balance in elderly women. AB - This experimental field study examined the potential usefulness of mental practice for improving physical performance in health care. Ideokinetic facilitation, which involves the use of idealized visual and kinesthetic mental images, was used as mental practice. Thirty-six women over the age of 70 were assigned to one of three intervention groups: Group A, nonsense; Group B, relaxation; or Group C, ideokinetic facilitation. Baseline and final measures of one-legged balance time were compared after a three-day intervention period. Results showed significant improvement between baseline and final measures within Group C only (t = 2.64, p less than or equal to .05). The improvement in Group C, however, was not significantly more than the improvement in Groups A and B. This study suggests that mental practice of a physical task can improve performance and may be of use to the physical therapy clinician. PMID- 4034668 TI - Reliability of goniometric measurements in patients with Duchenne muscular dystrophy. AB - Previous studies of reliability of goniometric measurements have produced varied findings suggesting the need to document further the reliability of measuring range of motion in different patient groups. The purpose of this study was to determine the intratester and intertester reliability of goniometric measurements of seven common upper and lower extremity joint limitations in children with Duchenne muscular dystrophy. Five physical therapists participated in the study. The procedure and order of measurements were standardized. Results showed that intratester reliability for all measurements was high (ICC = .81 to .94), but intertester reliability showed a wide variation (ICC = .25 to .91). The results of this study indicate the need to use the same examiner for long-term follow-up and for assessing results of specific treatment interventions. PMID- 4034669 TI - Lumbar traction: its effect on respiration. AB - The purpose of this study was to examine the effects of lumbar traction on inspiratory vital capacity (IVC), tidal volume (TV), and respiratory rate (fb). Using an 8-L recording spirometer, we measured the above values on 30 healthy volunteers during three conditions--lying supine, lying supine with a traction garment applied, and lying supine with the traction garment and a distractive force applied. The differences in IVC, TV, and fb among the three conditions were examined by using an analysis of variance for repeated measures followed by a Tukey test. Statistically significant differences were found for IVC, TV, and fb among the three conditions (p less than .001). The results indicated that IVC and TV were lowest and fb was highest when the distractive force was applied to the traction garment. We suggest that when lumbar traction is used for patients who have respiratory disease, the patients should be observed closely for signs of respiratory distress during the first few treatments. PMID- 4034671 TI - Physical therapy competencies in rheumatology. AB - Physical therapists and rheumatologists in the United States were surveyed to determine what they perceived as the necessary competencies in rheumatology for the entry-level physical therapist. Physical therapists in clinical education programs (n = 100), those who belonged to the Arthritis Health Professionals Association (n = 108), and rheumatologists belonging to the American Rheumatism Association (n = 80) responded to a questionnaire consisting of items related to educational variables of interest, professional experience, and 80 competencies. The respondents determined that 35 competencies were absolutely essential, 39 were frequently essential, and 6 were useful but not essential. Identification of these competencies should assist the faculty in physical therapy educational programs to prepare the entry-level physical therapist to be competent to treat arthritis patients. PMID- 4034670 TI - Effects of an inverted position on blood pressure, pulse rate, and deep tendon reflexes of healthy young adults. AB - This study reports the effects of an inverted position on pulse rate, blood pressure, and deep tendon reflexes of the biceps muscle, triceps muscle, and Achilles tendon. Twenty healthy adults were used as subjects. We collected data both before and after the subjects were in the inverted position for eight minutes on a specially designed tonic labyrinthine inverted table. A significant decrease in systolic blood pressure and all tendon reflexes was observed along with a significant increase in diastolic blood pressure (p less than .05). Pulse rate showed no change. The findings indicate that the inverted position is likely to be effective for decreasing muscle tone and systolic blood pressure. Although this study used healthy subjects, the inverted position may be used as a therapeutic technique, provided the clinician monitors closely the physiological effects on patients. PMID- 4034672 TI - Wedge maneuver message. PMID- 4034673 TI - New enzymatic changes of L-cystathionine catalyzed by bovine tissue extracts. AB - L-Cystathionine was used as substrate for enzyme systems prepared by heating bovine tissue extracts in the presence of pyruvate at 60 degrees C for 10 min. Analysis of the products indicated that the systems converted L-cystathionine into the cyclic ketimine form which was detected by its spectral properties and by chromatography on the amino acid analyzer. Alanine, alpha-aminobutyrate and cystine were also produced. Pyruvate and alpha-ketobutyrate enhance the production of the ketimine by liver, kidney and heart extracts, and are necessary for the brain extracts: alpha-Ketoglutarate is much less effective and its presence favors the production of homocystine by all the extracts. Homocystine was found in the brain incubates when any of the ketoacids assayed were added. The overall reaction is explained by the action of heat stable cystathionine gamma-lyase and beta-synthase which produce alpha-ketobutyrate and pyruvate used for the transamination of the remaining cystathionine to the monoketoacid. This last compound cyclizes spontaneously into the ketimine form thus avoiding the removal of the second amino group. This represents a new nontransulfurative path leading to the production of a seven membered etherocyclic product whose biochemical implications are yet unexplored. PMID- 4034674 TI - Contrast enhancement of spontaneous animal CNS tumors with gadolinium DTPA: a correlation of MRI with x-ray CT. AB - A visual comparison was made between both pre-contrast and post-contrast x-ray computerized tomographic images (X-CT) and magnetic resonance tomographic images (MRI) of spontaneous CNS tumors in three animals. The contrast agents, HypaqueR 76 (X-CT) and Gadolinium DTPA (MRI), were administered as an intravenous bolus injection. The parameters for comparison of pre- and post-contrast features included: lesion discrimination, demarcation, and intensity and pattern of enhancement. Necropsy specimens were included to correlate the anatomic fidelity of scan appearances for each modality and to establish a final diagnosis. There was good visual correlation of the lesion site with both X-CT and MRI. The intensity of lesion enhancement with the contrast reagents was similar for each modality but there were subtle differences in the pattern of enhancement. Overall, MRI in conjunction with the contrast agent Gadolinium DTPA, was as good or better at delineating the presence and extent of CNS tumors than contrast enhanced X-CT. Contrast agents may be necessary to provide increased lesion detectability and delineation when imaging with magnetic resonance. PMID- 4034675 TI - NMR in vitro measurements: a quality control study of the RADX table-top spectrometer. AB - A series of experiments was performed to evaluate the accuracy and reproducibility of relaxation values obtained by two RADX table-top spectrometers operating at 5 MHz (R5) and 10 MHz (R10) respectively. The output (T1, T2, and proton content) of each machine was compared (for tissue specimens and paramagnetic solutions) to reference spectrometers. In the range of tissue T1's, R5 overestimates T1 by approx. 10% and R10 underestimates by approx. 23%. For tissue specimens, the T2 output of both machines is within 3% of the reference facility. Proton content values correlate well with the % wet weight of tissues (y = .46x + 24, r = .85) but accuracy deteriorates badly if tissue T1 greater than 400 msec or T2 greater than 300 msec. The output of both machines is accurate and reproducible within 5% over the range of tissue relaxation values (biological fluids excluded). PMID- 4034676 TI - 31P-NMR studies on the energy metabolism of the living rat brain using a surface coil method. AB - We have examined the changes of the energetic metabolic state of rat and mouse brains under hypoxic hypoxia or ischemia using a 31P-NMR spectrometer with a surface coil. The NMR spectrometer has a super-conducting magnet providing a homogeneous magnetic field of 6.3 tesla. A probe was remodelled to accommodate an experimental animal in it. The animals were anesthetized with 1.0% or 1.5% halothane throughout the experiments. The optimal measurement conditions were a 90 degrees pulse width of 20 microsecond, and a 2 sec pulse repetition time. 200 acquisitions of FIDs was required for high spatially resolved signals. The Pcr/ATP ratio of the live, anesthetized rat brains was 1.76 +/- 0.46 (n = 8) for cerebra and 1.63 +/- 0.11 (n = 4) for cerebella. That of gerbil brains was 1.23 +/- 0.09 (n = 4). The Pcr/ATP ratio did not show any significant changes under both the conditions of hypoxic hypoxia or ischemia. The value of Pcr/Pi ratio decreased in the hypoxic conditions. The level of Pcr. of rat cerebrum decreased by 76.8 +/- 10.5% at 10% oxygen and by 57.3 +/- 15.7% at 5% oxygen compared with the value of 20% oxygen. The ATP level in the rat brain also decreased according to the degree of hypoxia. Cerebral ischemia was produced in the gerbil by ligation of the common carotid artery. The levels of Pcr. and ATP were severely depressed in the ischemic hemisphere but those of the intact side remained normal. PMID- 4034677 TI - Retardation of embryogenesis by extremely low frequency 60 Hz electromagnetic fields. AB - Fertilized Medaka fish eggs were used to determine if electromagnetic fields, designed to simulate those beneath a high voltage power line, have biological effects on vertebrate embryo development. The newly fertilized eggs were exposed to a 60 Hz electrical field of 300 mA/m2 current density, a 60 Hz magnetic field of 1.0 gauss RMS, or to the combined electric plus magnetic fields for 48 hours. No gross abnormalities were observed in any of the embryos as they developed, but significant development delays were seen in those embryos exposed to either the magnetic or to the combined electromagnetic fields; delays were not seen in the embryos exposed to the electrical field. Thus, a 60 Hz magnetic field like that encountered in a man made powerline environment was shown to retard development of fish embryos. PMID- 4034678 TI - Proton nuclear magnetic resonance spectra of excised rat brain. Assignment of resonances. AB - We have recorded 1H NMR spectra of excised rat brain at 361 MHz using two different water suppression pulse sequences. The assignment of the resonances has been carried out in perchloric acid extracts and subcellular fractions. Our results show that cytosolic proteins, membrane phospholipids and 16 different metabolites contribute to the observed spectra. The new resonances assigned allow the direct observation of myo-inositol and urea. Moreover, changes in the spectral pattern upon anesthesia, ischemic exposure of the brain and age of the rat have been recorded and correlated with the compounds producing the spectra. PMID- 4034679 TI - Influence of Mn(II) on NMR relaxation times of biological fluids. AB - The extent that various concentrations of the paramagnetic metal ion manganese [Mn(II)] affect nuclear magnetic resonance (NMR) relaxation times was studied in vitro. Serial dilutions of Mn(II) were prepared in distilled water, 4% human serum albumin, dog plasma, dog gallbladder bile, and dog hepatic bile. T1 and T2 of each were measured at 10.7 M Hz using magnetization recovery and spin-echo radiofrequency sequences, respectively. The results show that relaxation rates (1/T1 and 1/T2) increase in a linear manner with increasing concentration of Mn(II) in all of the solutions tested. Mn(II) dissolved in dog gallbladder and hepatic bile, dog plasma, and 4% human serum albumin reduced relaxation times to a greater extent than Mn(II) in water. T1 times were reduced to a greater extent than T2 values. Thus, in T1 weighted magnetic resonance images, the NMR signal used to produce images would be more sensitive to the presence of Mn(II) in these biological fluids than in water. Furthermore, the magnitude of this in vivo effect of Mn(II) on NMR relaxation parameters depends not only on the concentration of this paramagnetic ion, but also on the constituents comprising the biological fluids (intra- and extracellular water, bile, plasma) and the nature of the chemical molecular interactions between these constituents and Mn(II). PMID- 4034680 TI - Effects of protracted exposure to low intensity radio frequency fields on CHO cells in culture. AB - This study was performed in order to investigate the biological effects of chronic exposure to low intensity radio frequency fields. By using CHO cells in culture, it was possible to extend exposure to several cell generations. The RF field consisted of a 27 MHz magnetic field (6 A/m), which produces a specific absorption rate of 1 W/kg. Exposure was continued for two to five days. The cells were then studied with respect to certain cell biological parameters: vital staining, plating efficiency, growth rate, volume and physical properties of the intracellular water, as measured by NMR. Scanning electron microscopy studies were also performed. A significant difference between exposed and control cells was found only with respect to intracellular water. A 10% decrease in line width which may indicate a corresponding increase in the spin-spin relaxation time was noted after exposure. A change in the colony forming pattern was also observed in thin cultures after two days of exposure. PMID- 4034681 TI - The comparative influence of anesthetics on the in vitro proton NMR relaxation times in rat liver. AB - To determine the effect of anesthetics on liver relaxation times in rat, two experiments were performed. In the first experiment, normal and protein-depleted rats underwent total hepatectomy under ether anesthesia or following decapitation. In the second experiment, livers were excised from normal rats under ketamine or pentobarbital anesthesia, or following decapitation. Hepatic T1 and T2 were measured for all animals using a RADX 10 MHz spin analyzer. Ketamine produced T1 values significantly different from decapitation. Ketamine, pentobarbital, and ether in normal animals all produced T2 values significantly different from decapitation. It is apparent that anesthetization of rats prior to in vitro measurement of hepatic relaxation times is not equivalent to decapitation; nor are the anesthetics examined equivalent to one another. PMID- 4034682 TI - The effect of lateral mobility on the binding and reaction rate at membrane sites. AB - The rates of membrane processes like transport, hormone action and enzyme reaction depend on the prevailing temperature. Arrhenius plots of such rates show a break at the phase transition temperature. We have very little insight into the molecular mechanism of the effect of phase transition on the membrane phenomena. In general above this temperature there is an onset of two dimensional mobility of the surface sites. Here, we point out that the binding of ligands to these sites should then be described by an adsorption isotherm appropriate for mobile rather than fixed sites. This introduces an additional factor in the rate equation, which correlates well with the observed changes in the rates at membrane sites on gel to liquid crystalline transition. PMID- 4034684 TI - Physiology laboratories quantifying gas exchange in health and disease. PMID- 4034683 TI - Dependence of magnetic resonance image (MRI) intensity values on relaxation times, pulse intervals and other signal attenuation factors. AB - Magnetic resonance image (MRI) pixel intensities were investigated using a phantom containing several uniform size chambers filled with solutions of known relaxation times, as well as head scans of patients and volunteers. Intensities were measured with a variety of pulse intervals typically used for imaging with spin echo, (SE) and inversion recovery (IR) sequences at 0.15 Tesla using the back projection (R-THETA) method, and at 0.27 Tesla using the 2-dimensional Fourier transform (2DFT) technique. The results were compared with the calculated dependence of MRI signal intensity on relaxation times and pulse interval parameters using the well known functions containing exponential forms. The experimental and the calculated pixel intensity time dependence did not always agree. We infer that factors other than the conventional functions for T1 and T2 signal decay are important. These factors may include the attenuation of the radiofrequency (RF) signals through inhomogenious lossy dielectric materials (e.g., tissues and organs), the location (coordinate) of the portion of the sample to be imaged relative to the RF coils, and the timing and amplitude of gradient pulses relative to the RF input and the detected signals. The flow velocity and diffusions are also important determinants of the signal from blood vessels and body fluids. We point out the necessity for further investigation toward more comprehensive understanding of MRI intensities. PMID- 4034685 TI - Regulation of energy balance. PMID- 4034686 TI - Age effects on passive avoidance behavior of vasopressin-deficient Brattleboros. AB - Experiments in which vasopressin-deficient Brattleboros were tested in a passive avoidance procedure have yielded contradictory results. Some investigators observed the passive avoidance behavior of these subjects to be inferior to that of normal controls, while others failed to observe such differences. Inspection of the literature suggested that age differences between subjects which participated in these experiments might be responsible for the discrepancy. In the present experiment, HO-DI and HE Brattleboro rats of different ages were tested in the standard passive avoidance task. Passive avoidance performance of HO-DIs was, indeed, influenced by the age of the subject at the time of testing; HO-DIs reentered the shock compartment sooner than HE at 35 days, but later than HE at 120 days. There was no difference between the two groups of subjects at 60 days. The percentage of HO-DIs which reentered the shock compartment on the post shock trial decreased with increasing age. PMID- 4034687 TI - Schedule-induced wheel-running: effects of exposure to the schedule. AB - Rats were given access to a running wheel from a chamber where milk was delivered according to a fixed-time 1-min schedule. For most animals the effect of the schedule was to decrease wheel-running rate below that during massed reinforcement control sessions. With further exposure to the schedule wheel running rate tended to increase and a well-defined temporal pattern developed. Subsequent exposure to the control condition caused an initial increase and then, in most cases, a decline in wheel-running rate. Re-exposure to the schedule increased wheel-running rates in three out of four subjects and the temporal pattern developed more rapidly. Judgement as to whether a particular behavior pattern is schedule-induced or not can only be reliably made when there is strong evidence that the overall rate and temporal pattern of the behavior are stable. Wheel-running appears to be a schedule-induced behavior under some experimental conditions. PMID- 4034688 TI - Effects of oestradiol 17B, progesterone and testosterone upon proceptivity and receptivity in ovariectomized common marmosets (Callithrix jacchus). AB - The sexual behaviour of eight pairs of marmosets was observed during blocks of 30 minute tests after the ovariectomized female partners were treated with physiological doses of testosterone, oestradiol and progesterone. The effects of an intra-vaginal progesterone treatment were also investigated. Pre-ovulatory levels of oestradiol significantly increased the females' proceptive and receptive tongue-flicking displays and reduced the percentage of mounts refused. Mid-luteal levels of progesterone, by comparison, virtually abolished proceptive and receptive tongue-flicking and significantly increased mount refusals. Testosterone treatment was without effect. Vaginal application of progesterone unlike subcutaneous implantation of the hormone did not significantly alter the females' sexual behaviour. These results indicate that central actions of oestradiol and progesterone upon proceptivity and receptivity may occur in this primate, although further research using intra-cranial implants of these steroids is required to test this hypothesis. PMID- 4034689 TI - Avoidance and escape components of leg position learning in the prothoracic and mesothoracic ganglia of the cockroach, P. americana. AB - Prothoracic and mesothoracic legs of headless cockroaches with only a ventral nerve cord were trained to lift their legs when shock occurred. The prothoracic leg showed both avoidance learning (a decrease over time in the frequency of leg extension) and escape learning (a decrease in extension duration following shock receipt). The mesothoracic leg showed avoidance learning as fast and as well as the prothoracic leg but was unable to support escape learning. Furthermore, the avoidance component of prothoracic learning showed longer-term retention of several hours whereas the escape component showed only shorter-term retention which did not last 15 minutes. PMID- 4034690 TI - State-dependent learning following electrical stimulation of the hippocampus: intact and split-brain rats. AB - In experiment 1, electrical stimulation of the posterior hippocampus was shown to produce state-dependent learning (SDL) for a step-out inhibitory avoidance task in rats. Stimulation sites in either the right or left hippocampus were equally effective in producing this effect. Similarly, the presence or absence of afterdischarge (AD) following the stimulation did not differentially affect performance on the task. In experiment 2, forebrain bisection ameliorated the behavioral deficits in the animals receiving stimulation before testing but not before training (N/S group), while those stimulated before training but not before testing (S/N group) remained impaired; thus, providing a demonstration of asymmetrical SDL. Variations in extent of the commissurotomy differentially affected the laterality of the afterdischarge but not the performance in the SDL task. Speculation as to the mechanisms of this SDL effect was presented. PMID- 4034691 TI - Periodic water availability is not a potent zeitgeber for entrainment of circadian locomotor rhythms in rats. AB - Entrainment of tilt-cage measured circadian activity rhythms to a 2 hr daily period of water availability was assessed in rats fed either an oil-chow mash, which rats readily consume in the absence of water, or dry pellet chow, which rats less readily consume in the absence of water. Four of 6 pellet fed rats but only 2 of 14 mash fed rats exhibited entrainment to water access. Periodic water availability, unlike periodic food availability, thus does not appear to be a potent zeitgeber for circadian activity rhythms in the rat. The entrainment that does occur in some rats may result from shifting of food intake to coincide with the availability of water. PMID- 4034692 TI - Participation of cholinergic and adrenergic synapses of the medial septal area (MSA) in the natriuretic and kaliuretic responses to intraventricular hypertonic saline (NaCl). AB - The microinjection of hypertonic sodium chloride into the third ventricle elicits natriuresis and kaliuresis in rats following water loading. These responses were blocked by atropine or phentolamine microinjection into the MSA. The data suggest the interaction between periventricular areas sensible to changes of sodium concentration in the cerebrospinal fluid (CSF) and MSA. Cholinergic and alpha adrenergic synapses of MSA are involved in this interaction which regulates renal sodium excretion. PMID- 4034693 TI - Adipose tissue mobilization is unaffected by obesifying hypothalamic knife cuts. AB - Unilateral electrolytic lesions of the medial hypothalamus have previously been reported to spare starvation-induced lipid mobilization from the ipsilateral retroperitoneal fat pad. This suggests that deficient lipid mobilization contributes to the enhanced lipid deposition which results when such lesions are bilateral. In contrast, unilateral parasagittal hypothalamic knife cuts, which also obesify when bilateral, failed to prevent starvation-induced ipsilateral lipid mobilization. This finding indicates that impairment of neurally mediated lipid mobilization is probably neither a necessary nor a sufficient feature of hypothalamic obesity. PMID- 4034694 TI - Dehydration-induced sodium appetite in rats. AB - The effect of 24 hr water deprivation on Na balance was studied in rats. Under baseline conditions, the animals had free access to food and water. During water deprivation, Na excretion was increased, Na intake (i.e., food intake) was decreased and Na deficits of 0.8-1.0 mmol were incurred. During the 24 hr period immediately following the deprivation period when water was returned, Na excretion was decreased and Na balance was restored to baseline or pre deprivation level. In a second series of experiments, under baseline conditions, the animals had free access to food, water and 0.5 M NaCl. During water deprivation with NaCl solution withheld, Na excretion was not changed relative to baseline but Na deficits of 0.8-1.0 mmol were incurred due to decreased Na intake. During the 24 hr period immediately following deprivation when both water and NaCl solution were returned, intake of the hypertonic NaCl solution was increased and Na balance was restored. In a third series of experiments, under baseline conditions, the animals had free access to food, water, 0.5 M NaCl, 0.5 M KCl, 0.25 M of MgCl2 and 0.25 M CaCl2. During the 24 hr period following water deprivation and also the withholding of the electrolyte solutions, the appetite induced was predominantly for NaCl. The results suggest that the Na appetite observed subsequent to a period of water deprivation may be due to Na deficiency. PMID- 4034695 TI - Effects of size hierarchy on surfacing behaviour and conversion rate in an air breathing fish Channa striatus. AB - Effects of size hierachy on surfacing behaviour and food conversion rate in relation to density and feeding frequency were studied in Channa striatus. In general, crowding increased surfacing frequency in all the weight classes, but affected the food conversion rate of small individuals alone. At any tested density, conversion rate of smaller individual was depressed by the presence of larger individuals; increased feeding frequency did not compensate the negative effects of density. The possible reasons for growth inhibition are: (1) The smaller individuals spend much of their time and energy to escape from the aggressive larger ones than on feeding, and (2) the smaller individuals spend a considerable amount of assimilated food energy on increased surface activity. Unlike density, frequency of feeding improved the conversion rate of both the weight classes and it suggests that the larger individuals could compensate the negative effects of crowding by increased feeding. PMID- 4034696 TI - Role of the inferior colliculus in the inhibition of acoustic startle in the rat. AB - Fifteen rats were tested for amplitude reduction of the acoustic startle response using auditory and visual prestimuli. Eight subjects then received large lesions of the inferior colliculus, and the remaining subjects served as normal controls. All animals were reassessed on a post-test identical to the pre-test. In addition, all subjects were tested for latency reduction of startle using auditory prestimuli. There were no significant differences between groups on the pre-test for startle amplitude, visual amplitude reduction, or auditory amplitude reduction, nor did the control group differ significantly on these measures from pre-test to post-test. After surgery, the lesion group displayed a large, significant increase in startle amplitude. Auditory prestimuli were no longer effective in reducing startle amplitude in this group, but visual prestimuli still produced reliable amplitude reduction. Both groups displayed reliable latency reduction to auditory prestimuli; the groups were not significantly different from each other on this measure. These data support the proposition that the inferior colliculus is part of a neural circuit for startle amplitude reduction by auditory prestimuli. PMID- 4034697 TI - Involvement of the anterior insular gustatory neocortex in taste-potentiated odor aversion learning. AB - When an odor conditioned stimulus (CS) precedes illness (unconditioned stimulus; UCS), rats acquire relatively weak odor aversions. Conversely, when a compound odor-taste (flavor) CS precedes illness, rats acquire robust aversions both to the odor and to the taste components of a compound flavor CS. Thus, tastes potentiate odor-illness aversions during toxiphobic conditioning. Such conditioning effects have been referred to as taste-potentiated odor aversion learning (POA). Previous neurobehavioral experiments have shown that the anterior insular gustatory neocortex contributes to conditioned taste aversion (CTA) learning. The present experiment examined the involvement of the anterior insular gustatory neocortex in CTA learning and POA learning. To that end, four distinct groups of rats received bilateral electrolytic lesion placements in the orbitofrontal neocortex, the "somatic" gustatory neocortex, the anterior insular gustatory neocortex or the posterior insular neocortex. Control animals received anesthesia only. Subgroups of animals thereafter received aversion conditioning using either an odor (almond) CS or a compound odor-taste (almond-saccharin) CS. Aversions to the almond odorant and/or saccharin tastant were evaluated during extinction. Results indicated that animals lacking orbitofrontal neocortex or posterior insular neocortex acquired normal CTAs and POAs. Animals lacking somatic gustatory neocortex exhibited impaired CTA learning, yet those animals showed normal POA learning. Lesions centered in the anterior insular neocortex impaired both CTA learning and POA learning. These results demonstrate that the insular gustatory neocortex is uniquely involved in the higher-order integration of odors, tastes and illness. PMID- 4034698 TI - Hibernation "trigger" alters renal function in the primate. AB - Macaque monkeys acclimatized to a restraint chair were fitted with indwelling venous and urinary catheters. After basal rates of urine production and creatinine clearance were determined, a 50 mg dose of plasma dialysate albumin fraction obtained from the woodchuck was administered intravenously in a total volume of 2.5 ml. Plasma fractions were collected during the winter interval of hibernation (hibernation "trigger" or HT), or during the summer active (SAWA) period. Although the SAWA fraction exerted no effects on renal function, HT caused a significant reduction in creatinine clearance. In addition, a tendency toward reduced urine flow and creatinine production occurred following the HT infusion. These findings suggest that over and above the hypothermia, aphagia and opioid-like behavioral depression induced by HT, the albumin fraction (HT) present endogenously in the woodchuck during winter torpor, exerts a direct action on the kidney of the primate, possibly on the mechanisms underlying glomerular filtration and the tubular reabsorption process. PMID- 4034699 TI - Mapping of open-field behavior in rats and integration of various independent study results. AB - Open field behavior of four treatment groups was plotted on a map by factor scores which were derived from principal component analysis. The treatment consisted of electric shock, extensive stroking, testing under a very dim-light condition, or testing after habituation to the field. Five measures were used: ambulation, penetration into the inner square, rearing, defecation, and urination. The first two principal components accounted for 93% of the total variance in the data. By using the four treatment groups for reference, the manner in which results of independent studies can be plotted on a map, and how the interpretation of results can be facilitated, were demonstrated with some examples. A table composed of scores of eta squared for the four groups was also presented for reference and to facilitate integration of the results of various independent studies. PMID- 4034700 TI - An investigation of the factors affecting development of frontal cortex self stimulation. AB - Intracranial self-stimulation (ICSS) of the medial prefrontal cortex (MFC) is acquired gradually, taking 4 or more days to establish. One explanation for this finding is that the stimulation becomes more rewarding with repetition. Four experiments were conducted to test this hypotheses. In Experiment 1, the MFC ICSS frequency thresholds remained constant over the first 3 weeks of testing while the rate of lever pressing response increased. In Experiment 2, it was found that acquisition of MFC ICSS was much more rapid when a motorically simpler response (nose-poking) was employed. Similarly, Experiments 3 and 4 further demonstrated that response factors such as task complexity may ultimately determine the rate of development of frontal cortex ICSS. Overall, these data suggest that independent of the rewarding effects of MFC stimulation there are other effects that initially interfere with learning of complex operant responses. PMID- 4034701 TI - Response to NaCl taste in mixture with HCl by sodium deficient rats. AB - Sodium deficient, adrenalectomized rats and nondeficient control rats were offered, for 20 min, a mixture of 0.1 M NaCl and 0.02 N HCl. The sodium deficient rats drank substantial amounts whereas control animals were essentially indifferent to the mixture. Further tests on the sodium deficient rats with a stronger NaCl concentration in the mixture did not alter the amount drunk, which was about 1/3 the amount ingested of singly presented 0.1 NaCl. These results suggest that the sodium deficient rat can recognize the similarity of the mixture to NaCl but that the other mixture component influences the behavioral outcome in a way other than simple intensity suppression. PMID- 4034702 TI - Nutrient composition: effects on appetite in monkeys with oral factors held constant. AB - The effects of macronutrients on appetite and total caloric intake in monkeys (Macaca mulatta) was studied using a new feeding and infusion system which yoked intragastric infusion of various nutrients to oral ad lib intake and removed the confounding factor of palatability from the assessment of nutrient effects on feeding behavior. A suction-activated liquid diet feeding system provided free access to a nutritionally complete diet, with 1 ml of diet delivered orally by pump with each discrete suck by the monkey. A second pump was yoked to the oral feeding pump and delivered various nutrients directly into the stomach via an implanted intragastric cannula. Thus, while oral diet composition remained constant, the net diet reaching the stomach varied over ranges of 28 to 77% carbohydrate, 16 to 65% fat and 7 to 36% protein. No significant differences in total caloric intake were observed between intakes of diets with net composition of high carbohydrate or high fat. When protein was increased to 36%, total caloric intake was generally reduced, and this effect was sustained for at least 3 weeks. Therefore, protein appears to have an increased specific satiating effect beyond the caloric content, when compared to carbohydrate or fat. PMID- 4034703 TI - Further evidence that histamine in hippocampus affects the exploratory behavior in the rat. AB - The effect of histamine (HA) and 3-methyl-histamine (3-MHA) in the hippocampus on hole-board behavior was studied. Male rats were microinjected stereotaxically into the hippocampus with 1 microliter of saline solution containing 9, 45 or 90 nMol of HA or 3-MHA. Five min later, all rats were tested for 5 min in a hole board and locomotor, rearing, grooming and head-dipping activities were measured by direct observation. HA inhibited rearing and grooming at all the doses used but it affected locomotor activity only at 45 and 90 nMol doses. There was no effect on head-dipping behavior. 3-MHA instead increased locomotor and head dipping activities at all the doses used and it did not change rearing and grooming. The present results give a further support for a physiological participation of HA in the hippocampus. PMID- 4034704 TI - [Modulation of cutaneous evoked potentials during the period preparatory to a reaction time task in the cat]. AB - Evoked potentials (EP) were elicited in four cats either when they sat still or when they performed a reaction time (RT) task. The foreperiod (FP) of the RT situation started with the cat placing his paw on a platform and ended 1.5 sec later with the vibration of the platform, used as a signal to withdraw the paw. The paw was electrically stimulated, once per trial, during the last second of the FP. Evoked potentials were recorded in the medial lemniscus (ML), in the thalamic nucleus centrum medianum (CM), in the internal capsule (IC) and over the anterior suprasylvian gyrus (ASSG). On the average, the EPs recorded in the CM, in the IC and over the ASSG (early and late waves) were significantly reduced during the FP. The EPs recorded in the ML did not show any significant change. The reduction in the EPs amplitude decreases along the FP, being the less at the time of arrival of the response signal. Neither the amplitude nor the time course of the EPs are correlated with the RT duration. These results are discussed with reference to the concepts of preparation for movement and of anticipation of the response stimulus. PMID- 4034705 TI - Effects of thyroid hormones on the hippocampal glial cells of fasting rats. AB - The effects of the oral administration of thyroid hormones on the hippocampal glial cells in fasting or fed adult rats were studied. The hormone treatment and/or fasting were done during two periods of five days interpolated by ten days without any hormone treatment or fasting. Prominent histological changes and increased number of glial cells were observed in the hippocampus of rats when the thyroid hormone administration was associated with fasting. PMID- 4034706 TI - Relationship between autonomic and behavioral thermoregulation in the mouse. AB - Preferred ambient temperature (Ta) was measured in nine mice of the BALB/c strain using a temperature gradient. When tested over four consecutive days the mean preferred Ta was 30.9 degrees C. In another study using the same animals, metabolic rate, evaporative water loss, whole-body thermal conductance, and colonic temperature were measured at specific Ta's over a range of 18 to 34 degrees C. The preferred Ta of 30.9 degrees C was associated with the lower critical Ta (i.e., Ta below which metabolic rate increased) a 57% elevation in evaporative water loss when expressed in units of mg water evaporated per ml consumed oxygen, a thermal conductance that was 92% above baseline levels, and a normothermic colonic temperature of between 37.0 to 37.5 degrees C. The data indicate that mice will select an environmental temperature associated with a minimal energy expenditure but a higher than minimal rate of evaporation and higher thermal conductance. PMID- 4034707 TI - Stress-induced analgesia evoked by intraperitoneal injection of hypertonic saline: evidence for its occurrence in vasopressin deficient rats. AB - Experiments were carried out to investigate whether vasopressin is involved in stress-induced analgesia. Intraperitoneal injection of hypertonic saline caused a significant and dose-related increase in the latency to the tail-flick response of the rat to noxious heat and was used as a stimulus for stress-induced analgesia. Neither the pituitary nor opioid peptides appeared to be involved, since the response occurred in hypophysectomized rats and was not reduced by the opiate antagonist naloxone. Furthermore hypertonic-saline analgesia was clearly potentiated in hypophysectomized rats in comparison to sham-operated controls. Hypertonic-saline analgesia was also observed in vasopressin-deficient (homozygous Brattleboro) rats similar in both magnitude and duration to that in normal rats of the same strain (Long Evans). It was concluded that vasopressin was not involved in stress-induced analgesia evoked by hypertonic saline. PMID- 4034708 TI - A comparison of shock avoidance learning in headless cockroaches in leg-lifting and lowering task. AB - Headless cockroaches were trained either to lift or to lower the prothoracic leg to avoid electric shocks. The learning process in both cases was very distinct. However, the learning performance in the lifting was better than in the lowering task. The reason for this poorer learning in the lowering task is due to the unconditioned leg raising movement of the animals to electric shocks. This unconditioned response affects the headless cockroaches avoid shocks in the lifting task by escape learning, whereas they avoid shocks in the lowering task by true avoidance learning. Injection of 30 microliter of Ringer's solution has no significant effect on the learning process in the lifting task. In the lowering task, however, Ringer's solution impairs the learning ability considerably. Crude extract of corpora cardiaca strongly inhibits the learning of both tasks. PMID- 4034709 TI - Differential acquisition of a "working memory" task by the Roman strains of rats. AB - Twenty-eight male rats of the Roman strains-fourteen RHA (Roman High Avoidance) and fourteen RLA (Roman Low Avoidance)-were submitted to a positively reinforced task, the delayed reinforced alternation test (DRA), in a T-maze. Performances of RLA rats were significantly better than those of RHA; RLA rats also had higher VTE (vicarious trial and error) and spontaneous alternation (SA) scores. These data confirm the fact that RLA may acquire positively reinforced learning as rapidly, or even more rapidly, than RHA rats, and that the differences in active avoidance behavior between these strains depend more on differential freezing behavior than on learning and memory capacities. Since the delayed reinforced alternation is considered as a working memory test, our results suggest that the Roman strains could be used as a genetic model for the neurobiological study of this form of memory. PMID- 4034710 TI - Aversive consequences of jejunoileal bypass in the rat: a conditioned taste aversion analysis. AB - Jejunoileal bypass (JIB) surgery reduces food intake and body weight in obese humans and rats. Human bypass patients report visceral discomfort following surgery, and the present study assessed the aversive consequences of JIB in rats using a conditioned taste aversion paradigm. In Experiment 1 rats given a cherry flavored solution immediately after JIB surgery subsequently displayed a strong aversion to the cherry flavor compared to Bypass and Sham-Bypass control groups. Rats in Experiment 2 were familiarized with cherry solution prior to surgery and they did not display an aversion to the solution after receiving a JIB. In Experiment 3, Bypass rats who developed a cherry flavor aversion after JIB subsequently lost this aversion following reconnection of their intestinal tract. The rats in Experiment 4 displayed an aversion to a saccharin-flavored chow that was eaten shortly after JIB surgery, although the aversion was not as pronounced as that obtained with the cherry solution. The results suggest that JIB produces a persisting malaise in rats that may contribute to the feeding and weight inhibitory effects of the operation. PMID- 4034711 TI - Aversive effects of vagotomy in the rat: a conditioned taste aversion analysis. AB - Subdiaphragmatic vagotomy suppresses food intake and water intake in normal rats. Since human patients report some nausea and discomfort following vagotomy, the present study assessed the aversive consequences of vagotomy in rats using a conditioned taste aversion paradigm. Rats were given a total subdiaphragmatic vagotomy or sham vagotomy, and were then maintained on either plain water (Vag Water and Sham-Water groups) or a novel cherry solution (Vag-Cherry and Sham Cherry groups). When subsequently tested for their water vs. cherry preferences on postoperative days 6, 16, and 26, the Vag-Cherry group displayed a greater aversion to the cherry solution than did the remaining three groups. This result suggests that vagotomy produces visceral malaise in rats which may contribute to the feeding and drinking suppressive effects of the surgery. PMID- 4034712 TI - Behavioral perturbations in the vitamin K-deficient rat. AB - Anecdotal observations of the behavior of rats with a vitamin K-deficiency suggested that this deficiency was associated with hypoactivity, general malaise, and a lack of exploratory behavior. These observations were pursued by assessing locomotor activity in a circular photocell-monitored track, open-field activity, and radial-arm maze performance in rats rendered vitamin K-deficient by dietary depletion or by warfarin treatment. There was a significant reduction (approximately 25% at the median) in the locomotor activity of dietary vitamin K deficient rats compared with rats fed a control diet. In the open-field, warfarin administration was associated with a significant shift from more exploratory behaviors to less exploratory behaviors. Consistent with these findings, radial arm maze assessment showed a comparative reduction in locomotor activity in the dietary vitamin K-deficient rats with no alteration in performance, i.e., short term memory. These animal behavioral studies suggest that sub-clinical and clinical vitamin K-deficiency may contribute to physical and psychiatric symptomatology. PMID- 4034713 TI - Differential effects of perinatal androgen treatment on sexually dimorphic characteristics in rats. AB - Rats were treated with testosterone propionate (TP) or oil (O) beginning in midgestation (group TTT), late gestation (group OTT), neonatally (group OOT), or were left untreated until adulthood (group OOO). At 40 days of age all animals were gonadectomized, received implants of TP in silastic capsules, and were tested in subsequent weeks for masculine copulatory behavior and ex copula phallic responses. Postmortem measures were taken of genital structures and of sexually dimorphic spinal nuclei. Males treated perinatally with androgen were unaffected or exhibited reduced masculinization except on two measures, i.e., number of penile flips and number of cells in the dorsolateral motor nucleus of the lumbar spinal cord, which reflected virilization greater than in normal males. All perinatally androgenized females showed virilization on almost every measure taken of their morphology and behavior. Relative to OOO females, the greatest increases in masculinization were evident in OOT and OTT females. No additional masculinization was detected in TTT females. Only among the TTT rats were males not reliably more masculine than females, but that usually was due to the reduced masculinization of TTT males. Four broad classes of influence characterized the effects of perinatal androgen treatment; these classes may reflect differences in the developmental courses of the variables measured. PMID- 4034714 TI - Dietary self-selection and the regulation of protein and energy intake in chicks. AB - Studies were conducted to determine whether chicks could regulate their protein intake independent of total energy intake in self-selection feeding trials. Day old White Mountain cockerels were reared in electrically-heated battery brooders and given access to either a 23% protein control ration (no choice) or two diets containing 10% or 60% protein with or without supplemental amino acids. The latter were added to either improve the dietary amino acid balance or to alter plasma and brain levels of free large neutral amino acids (tryptophan, isoleucine, leucine, valine, phenylalanine, and tyrosine) which have been implicated in the neuroregulation of feed intake. Both feed and water were provided ad lib, and the location of the feed troughs within each pen were changed daily. Body weights and feed intakes were measured daily, and total calorie and protein intakes were calculated. Chicks offered 10% and 60% protein diets with no supplemental amino acids exhibited reduced weight gains and markedly higher protein intakes as compared to birds fed either the control ration or those given a choice between 10% and 60% protein diets supplemented with methionine. The higher protein consumption by chicks fed the unsupplemented diets most likely was a result of an attempt to compensate for a dietary methionine deficiency. Chicks fed the 10% and 60% protein diets supplemented with amino acids grew at a slower rate than those fed the 23% protein control diet. In general, plasma and brain data did not support a proposed relationship between certain large neutral amino acid ratios and protein or energy intake. PMID- 4034715 TI - Brachium conjuntivum and rubrobulbar tract: brain stem projections of red nucleus essential for the conditioned nictitating membrane response. AB - The trajectory of the rubrobulbar tract in rabbit to the level of the accessory abducens nucleus is described: orthograde labeling of fibers of the rubrobulbar tract following horseradish peroxidase implants into red nucleus of 8 animals permitted ad hoc analysis of the effects of brain stem lesions on the rabbit's conditioned nictitating membrane response. Twenty-four rabbits, trained to give conditioned NM responses from both eyes, received unilateral lesions of the right pontine brain stem. Six of the 7 cases of post-lesion disruption of ipsilateral conditioned responding involved either ipsilateral brachium conjunctivum or the rubrobulbar tract. This finding, together with a reexamination of data from two related studies from this laboratory strongly support the conclusion that an essential premotor component of the conditioned NM response is a doubly decussating circuit from the interpositus nucleus of the cerebellum to magnocellular red nucleus, via brachium conjunctivum and its decussation, and from red nucleus caudally, via the ventral tegmental bundle and the rubrobulbar tract, to the accessory abducens nucleus, where motoneurons involved in the NM response are located. These findings are consistent with published reports on the essential role of interpositus nucleus of the cerebellum in NM conditioning. The possible role of the supratrigeminal reticular formation in this learned behavior is also discussed. PMID- 4034716 TI - Behavioral and neural gustatory responses in rabbit. AB - To provide more information on a potentially valuable preparation for studies in taste and appetite, we have examined the taste preferences (and aversions) and chorda tympani sensitivity of the rabbit. Adult male New Zealand rabbits were given a two-bottle preference test between water and various molar concentrations of NaCl, KCl, sucrose, sodium saccharin, quinine hydrochloride and HCl. The rabbits exhibited the expected preferences for sucrose and aversions for quinine and HCl. Unexpectedly, however, the rabbits exhibited only a mild preference for NaCl, a stronger preference for KCl, and an aversion to sodium saccharin. Multiunit discharges of the chorda tympani nerve to the same taste stimuli indicated that the anterior tongue receptors are acutely sensitive to KCl, NaCl and quinine, but not to sucrose, HCl and saccharin. The chorda tympani was more responsive to KCl than to NaCl. Dilute concentrations of both NaCl and sodium saccharin elicited a two-component response consisting of an immediate excitatory phase followed by a tonic inhibitory phase. This complex response pattern of the whole nerve to NaCl and sodium saccharin is discussed in relation to the impulse frequencies in hypothesized water-sensitive and salt-sensitive fibers. Both the behavioral and neural data are discussed in relation to similar data obtained in rat and hamster. PMID- 4034717 TI - Effect of sleep on cerebral DNA synthesized during shuttle-box avoidance training. AB - Female Wistar rats weighing 200 g were implanted with cortical electrodes and two intraventricular cannulae. Five days later they were given 3H-thymidine and exposed to shuttle-box training for four hours. They were then left free to sleep in the following three hours during which their EEG activity was recorded. In comparison with control animals (C), learning (L) and non-learning (NL) rats exhibited an increase in SS. In comparison to the EEG recording made the previous day, all animal groups displayed an increase in SS, but only NL rats suffered a decrease in PS(%). The specific radioactivity of DNA measured in several brain regions was tendentially lower in NL rats, but significance was achieved only in the cerebellum in the comparison between NL rats and C rats. No change occurred in liver. More marked and significant decrements in the DNA specific radioactivity of all brain regions were observed in the subgroup of NL rats displaying relatively high values of PS time in comparison to the analogous subgroups of C and L animals. Comparable decrements were present with regard to the subgroup of NL rats endowed with relatively low PS time. Less widespread and more limited changes were observed in the concentration of acid-soluble radioactivity. In addition, several significant correlations were detected by Spearman's analysis among behavioral, biochemical and sleep parameters. The results are consistent with the interpretation that the selective decrease in brain radioactive DNA observed in NL rats reflects a loss of DNA synthesized during the training period. The loss is related to the amount of post-training PS and is associated to a lengthening of the mean duration of PS episodes. It may be concluded that the loss of newly-synthesized brain DNA reflects the elimination of molecules associated with neural information devoid of adaptive value. PMID- 4034718 TI - Effects of naloxone and chlordiazepoxide on lateral hypothalamic self-stimulation in rats. AB - Lateral hypothalamic self-stimulation behavior of rats in an operant chamber was investigated under the treatments of the first injection of naloxone (5 mg/kg) or saline followed by the second injection of chlordiazepoxide (4 mg/kg) or saline. Both inhibitory effect of naloxone and facilitatory effect of chlordiazepoxide on self-stimulation response were statistically significant, but the interaction between the two effects was not obtained. The results indicate that the facilitatory effect of chlordiazepoxide upon self-stimulation is independent of endogenous opioid system. Further, the obtained effect of naloxone was discussed in terms of interaction of the drug with aversive, rather than rewarding, component of self-stimulation. PMID- 4034719 TI - Role of the pineal gland in circadian organization of diurnal ground squirrels. AB - Golden-mantled ground squirrels, Spermophilus lateralis, pinealectomized (pinx) or sham-pinx at 70 days of age, were maintained in a LD 10:14 photoperiod; phase angles of activity onset were 1.6 +/- 0.3 and 1.9 +/- 0.3 hr in advance of light onset, respectively, and did not differ significantly between the groups. Rates of phase shifting of the activity rhythm after a 6 hr phase advance in the LD cycle also were comparable for the two groups and stable re-entrainment was achieved in 11 days. The period of the free-running activity rhythm in constant light did not differ between the groups. As demonstrated previously in nocturnal rodents, the pineal gland exerts little if any influence on generation or entrainment of the ground squirrel diurnal circadian activity rhythm. The rodent pineal is neither a master circadian oscillator nor a significant component of the transduction process by which light entrains the circadian activity rhythm. PMID- 4034721 TI - Targets of learned food aversions in humans. AB - In order to determine whether some nutrients are more salient targets than others for the development of learned taste aversions a large group of normal human subjects were surveyed about their experiences with such aversions. The targets of these spontaneously occurring food aversions were identified and classified into general food categories. A prominent category for human aversions proved to be foods which were protein sources. This finding was similar to our observations in the clinical setting as well as those we have obtained using an animal model. It suggests that taste and/or postingestive properties of protein foods may make them particularly salient targets for food aversion learning. PMID- 4034720 TI - Histamine plays no part in schedule-induced polydipsia in the rat. AB - Twelve Sprague-Dawley male albino rats were tested with or without combined antagonism of peripheral H1 (using 2 mg/kg dexbrompheniramine IP) and H2 (using 32 mg/kg cimetidine IP) receptors for histamine prior to (a) drinking after 2.5 mg/kg histamine SC, (b) drinking after 24-hr water deprivation, and (c) drinking during the acquisition and maintenance of schedule-induced polydipsia (SIP) with a 45 mg Noyes pellet delivered every 90 sec. Such antagonism of histamine receptors abolished drinking elicited by exogenous histamine without inhibiting drinking after water deprivation. Moreover, histaminergic antagonism failed to prevent the acquisition and maintenance of SIP and failed to alter the distribution of contacts with the drinking spout during interpellet intervals. These findings demonstrate no role for endogenous systemic histamine in SIP. PMID- 4034722 TI - An avian vocalization detector. AB - A simple circuit to detect avian vocalizations is described. Adjustments of five different controls (frequency, bandwidth, amplitude, duration and spacing) allow the circuit to accurately detect the vocalizations of different ages and species of birds. Analyses of over 4000 peeps and 500 inter-peep intervals from 40 chicks and 16 ducklings showed that the circuit and an experienced observer agreed closely in the timing and counting of vocalizations. PMID- 4034723 TI - A method to section the corpus callosum in the rat. AB - A simply constructed instrument and a surgical procedure are described for transecting the corpus callosum in the rat. The callosum can be cut in its entirety, or the cut can be limited to anterior or posterior halves. The procedure obviates lateralized incidental damage. PMID- 4034724 TI - The time-structure of the anorectic effect of satietin. AB - The influence of anorectic doses of satietin, calcitonin, fenfluramine and amphetamine on the amount of food eaten, on the time elapsed before taking the first tablet (latency) and on the time-structure of food intake during a one hour feeding session, divided into four 15-minute periods, was measured in rats after one day starvation with a pellet-detecting eatometer. In contrast to fenfluramine, amphetamine significantly increased the time elapsed before taking the first tablet, indicating the stimulation of a satiety mechanism by fenfluramine and the inhibition of a feeding mechanism by amphetamine. In this test satietin and calcitonin acted like fenfluramine. The time-course of food intake was significantly different in the amphetamine and fenfluramine-treated animals, the latter ate more during the first 15-minute period. Satietin and calcitonin acted like fenfluramine in this test, too. The results are consistent with the view that satietin acts by activating a satiety mechanism. PMID- 4034725 TI - Mutations affecting replication and copy number control in plasmid mini-F both reside in the gene for the 29-kDa protein. AB - We have isolated and characterized cop, copts, and repam mutants of plasmid mini F after in vitro mutagenesis with hydroxylamine. cop mutants exhibit a copy number of about 10 per cell. The copts mutants are cold-sensitive and have, at 25 degrees C, a copy number of about 30-40 copies per cell, which drops to 4 copies at 42 degrees C. The cop and repam mutations affect the 29-kDa E protein. The Copts phenotype results from the simultaneous occurrence of two mutations, a cop mutation in the E protein and a temperature-dependent mutation (termed ecp) enhancing the Cop phenotype at low temperature. The latter new type of mutation is located within the DNA region 44.1-44.85F. Complementation experiments with plasmid cointegrates show that the wild-type gene is dominant over the cop allele. The nucleotide sequences of the cop and the repam mutations have been determined. PMID- 4034726 TI - Isolation and hypoglycemic activity of anemarans A, B, C and D, glycans of Anemarrhena asphodeloides rhizomes. PMID- 4034727 TI - Isolation and hypoglycemic activity of atractans A, B and C, glycans of Atractylodes japonica rhizomes. PMID- 4034728 TI - Purification and chemical properties of anti-complementary polysaccharide from the leaves of Artemisia princeps. PMID- 4034729 TI - [In vitro phagocytosis stimulation by isolated plant materials in a chemoluminescence-phagocytosis model]. PMID- 4034730 TI - Aqueous extract of valerian reduces latency to fall asleep in man. PMID- 4034731 TI - Studies on the Taiwan folk medicine; III. A smooth muscle relaxant from Onychium siliculosum, onitin. PMID- 4034732 TI - Pharmacological studies of piperine; I. Effects of piperine on transmural nerve stimulation. PMID- 4034733 TI - Isolation and hypoglycemic activity of lithospermans A, B and C, glycans of Lithospermum erythrorhizon roots. PMID- 4034735 TI - Isolation and hypoglycemic activity of aconitans A, B, C and D, glycans of Aconitum carmichaeli roots. PMID- 4034734 TI - Isolation and hypoglycemic activity of moran A, a glycoprotein of Morus alba root barks. PMID- 4034736 TI - Isolation and hypoglycemic activity of ephedrans A, B, C, D and E, glycans of Ephedra distachya herbs. PMID- 4034737 TI - Search for adenylate cyclase activator in medicinal plants. PMID- 4034738 TI - Study of hypoglycaemic activity of Cuminum nigrum seeds in normal and alloxan diabetic rabbits. PMID- 4034739 TI - The effect of biological variables on the anti-ulcerogenic effect of vegetable plantain banana. PMID- 4034740 TI - [Pyrrolizidine alkaloids with chromosome-damaging effects on human lymphocytes in vitro]. PMID- 4034741 TI - Effect of Triticum vulgare extract on DNA synthesis of mammalian cells. PMID- 4034742 TI - Mechanism of antihepatotoxic activity of atractylon, I: Effect on free radical generation and lipid peroxidation. PMID- 4034743 TI - Diuretic action of paeonol. PMID- 4034744 TI - Extracts of the ivy plant, Hedera helix, and their anthelminthic activity on liver flukes. PMID- 4034745 TI - Alkaloids of Lolium temulentum: isolation, identification and pharmacological activity. PMID- 4034746 TI - Coumarins from Polygala paniculata. PMID- 4034748 TI - Specific immunoassays for quinine and quinidine: comparison of radioimmunoassay and enzyme-linked immunosorbent assay procedures. PMID- 4034747 TI - Antibiotic properties of thiarubrine A, a naturally occurring dithiacyclohexadiene polyine. PMID- 4034749 TI - [Isopimpinellin--a furocoumarin from Heracleum sphondylium with chromosome damaging activity]. PMID- 4034750 TI - Muscle relaxant properties of aqueous extract of Lippia multiflora. PMID- 4034751 TI - The vascular actions of aqueous extract of Lippia multiflora. PMID- 4034752 TI - Effect of Aloe extract on peripheral phagocytosis in adult bronchial asthma. PMID- 4034753 TI - Alteration of neuroma formation by manipulation of its microenvironment. AB - In a primate model a histologic assessment of neuroma formation is reported. Three experimental groups were defined. Transected sensory nerves left adjacent to the incisional wound in an area of movement (wrist) were considered the control group. In the "proximally cut" group the same sensory nerves were positioned well proximal to the incisional wound. In the "muscle-implantation" group these nerves were placed in adjacent muscles. At 6 months a histologic assessment of the neuroma formation in the three experimental groups was carried out. Implantation of the sensory nerve into muscle significantly altered the regenerative potential of that nerve. The muscle completely surrounded the sensory nerve. The minimal neuroma that formed had significantly less scar tissue and contained nerve fibers that were of a smaller diameter and decreased density than either the control or the proximally cut group. There were no histologic differences between these latter two groups. However, regeneration into the overlying skin that was noted in the control neuromas was not seen in those nerves which had been proximally cut. PMID- 4034754 TI - Effect of glucocorticoid treatment on skin capillary blood flow and viability in cutaneous and myocutaneous flaps in the pig. AB - The effect of methylprednisolone treatment on skin-flap viability and capillary blood flow was studied in a series of four experiments. Intramuscular methylprednisolone injections (30 mg/kg per day), given in single or divided doses preoperatively or postoperatively, had no effect in augmenting skin viability in arterialized cutaneous, myocutaneous, or random skin flaps compared with the control. Capillary blood flow was studied in arterial buttock flaps and latissimus dorsi myocutaneous flaps raised on animals treated preoperatively with methylprednisolone or saline (control), and no significant difference in capillary blood flow was noted between the treatment and control flaps. It was concluded that methylprednisolone has no significant therapeutic effect either in increasing flap viability or in increasing capillary blood flow in skin flaps in pigs. PMID- 4034755 TI - Reconstruction of the pharyngoesophagus following pharyngoesophagectomy and irradiation therapy. AB - During the 5-year period between 1978 and 1983, a total of 56 individuals have undergone pharyngoesophageal reconstruction at our hospitals. To restore the continuity of the upper enteric tract, conventional skin flaps with or without the underlying muscle were used in 27 and a segmental free intestinal graft by means of microvascular technique was used in 29. Two-thirds of both groups received irradiation therapy before surgery. Fistula formation was encountered in 8 individuals who received a skin flap. This incidence was found to increase with the use of preoperative irradiation. In contrast, no patient developed a fistula among the 29 patients who received the segmental free intestinal graft. PMID- 4034756 TI - Onlay cartilage graft of the alar lateral crus for cleft lip nasal deformities. AB - The onlay cartilage grafting technique is described for treatment of unilateral or bilateral cleft lip nasal deformities. The alar cartilage is exposed through rim and intercartilagenous incisions. The cephalic half of the alar cartilage is excised, similar to the technique of traditional tip rhinoplasty. The harvested cartilage is applied to the intact caudal cartilage in layered fashion and secured with absorbable sutures. If necessary, successive layers may be added. These grafts provide a sturdy, yet delicate framework for a more normal appearing alar rim. We have performed this procedure on 16 patients, ages 10 to 41. Follow up intervals range from 13 to 40 months, with a mean of 19 months. Results have been rated good-to-excellent by patients and surgeons. There has been no recurrence of the deformity. The only complication has been one nasal vestibule synechia. PMID- 4034757 TI - Aerodynamic assessment of the results of pharyngeal flap surgery: a preliminary investigation. AB - Voice-quality (i.e., nasality) judgments are commonly used to evaluate the results of pharyngeal flap surgery. However, these are subjective judgments of questionable validity and reliability. This project was designed to systematically evaluate the outcome of pharyngeal flap surgery utilizing objective, quantifiable physiologic (pressure-flow) information. Thirty-one patients who had undergone pharyngeal flap surgery were selected. Pressure-flow measurements and perceptual judgments of speech were obtained following surgery. Results indicated that using pressure-flow criteria, only 52 percent of the outcomes were considered successful. Results also indicated that 35 percent of the cases were characterized by substantial nasopharyngeal airway obstruction. In the present study, these findings, along with the related perceptual phenomenon of denasality, were considered unsuccessful. Finally, results suggest that aerodynamic measurements can be used to assess other surgical techniques designed to correct velopharyngeal insufficiency. PMID- 4034758 TI - Palatal grafts for eyelid reconstruction. AB - A full-thickness graft of hard palate mucosa was used as the lining tissue for eyelid reconstruction in 11 patients over a 7-year period. An orbicularis musculocutaneous flap supplied cover and support. In all cases the mucosal graft was easily removed, convenient to handle, and took completely. The palate donor site reepithelialized by about 3 weeks postoperative and has remained healed and asymptomatic in all cases. In follow-up averaging 3 years, all the reconstructed lids have retained a stable and comfortable lid margin, with no instance of entropion or irritation. The outstanding virtue of palate mucosa for eyelid reconstruction is that it appears to retain most of its original size and stiffness over the long term and thus in a single layer can serve to replace both tarsus and conjunctiva. PMID- 4034759 TI - Long-term clinical outcome of immediate reconstruction after mastectomy. AB - Immediate reconstruction of a breast removed for treatment of carcinoma can be accomplished without altering the cancer-ablative surgical procedure. The theoretical possibility that reconstruction might compromise the cure rate has tempered enthusiasm for this approach. To test this issue, the relapse-free survival of 101 patients who underwent breast reconstruction in the immediate postmastectomy period was compared with that of 377 patients with breast cancer who underwent mastectomy without immediate reconstruction. This comparison was accomplished using multivariable statistical techniques to correct for baseline inequalities between the patient groups. After adjustment for the relevant prognostic factors, no significant difference remained between the two groups. We conclude that immediate reconstruction has no discernible adverse influence on the natural history of surgically treated breast carcinoma. PMID- 4034760 TI - Transfer of vascularized extensor tendons from the foot to the hand with a dorsalis pedis flap. AB - The use of the dorsalis pedis flap with vascularized extensor tendons was presented. An anatomic study has been carried out that has shown that the vascularization of the foot extensor tendons can be exclusively dependent on the blood contribution coming from the dorsalis pedis artery. In two cases that are presented and followed up for over a year after the surgery, the functional results obtained are good in the hand and aesthetically acceptable in the foot. PMID- 4034761 TI - Improving the accuracy of burn-surface estimation. AB - A user-friendly computer-assisted method of calculating total body surface area burned (TBSAB) has been developed. This method is more accurate, faster, and subject to less error than conventional methods. For comparison, the ability of 30 physicians to estimate TBSAB was tested. Parameters studied included the effect of prior burn care experience, the influence of burn size, the ability to accurately sketch the size of burns on standard burn charts, and the ability to estimate percent TBSAB from the sketches. Despite the ability for physicians of all levels of training to accurately sketch TBSAB, significant burn size over estimation (p less than 0.01) and large interrater variability of potential consequence was noted. Direct benefits of a computerized system are many. These include the need for minimal user experience and the ability for wound-trend analysis, permanent record storage, calculation of fluid and caloric requirements, hemodynamic parameters, and the ability to compare meaningfully the different treatment protocols. PMID- 4034762 TI - Reconstruction of the eyebrow in the pediatric burn patient. AB - We have reviewed our experience with reconstruction of eyebrow alopecia secondary to thermal injury in the pediatric patient. Reconstruction was performed with free composite strip grafts or vascularized island pedicle flaps. The complication rates for eyebrows reconstructed with vascularized island pedicles with respect to loss of a significant portion of the flaps (30.8 percent) and malalignment of the grafts (23.1 percent) were significantly greater (p less than 0.001) than the significant tissue loss (10.6 percent) or graft malalignment (7.9 percent) observed for free composite grafts. Hair density was more predictably restored with the free composite graft technique (p = 0.0004). The patients reconstructed with composite grafts had 89.4 percent acceptable results in contrast to 38.5 percent acceptable results obtained with the island pedicle technique. Based on these findings, we reserve the use of the vascularized island pedicle technique for male patients with unilateral alopecia and heavy hair density in the remaining eyebrow and in cases where free composite grafts have failed. The remaining patients are initially treated with free composite grafts with acceptable results in the overwhelming majority of cases. PMID- 4034763 TI - The protruding premaxilla and minimal median alveolar cleft: an unusual problem with a 12-year follow-up. AB - This case of a bilateral complete cleft lip with minimal alveolar cleft illustrated that recession of the protruding premaxilla will occur following lip closure even if no cleft of the secondary palate or other void exists. PMID- 4034764 TI - Free tongue composite graft for correction of a vermilion defect. AB - A case report of hemangioma of the vermilion border treated with excision and free composite tongue graft is presented. A technique of lip reconstruction utilizing a composite tongue graft in one step has been described. It constitutes an improvement over the tongue pedicle flap technique, which has been hitherto used and requires two stages. The indications and limitations of the technique have been discussed. PMID- 4034765 TI - A new method utilizing the bipedicle flap for reconstruction of the external auditory canal in microtia. AB - A new technique using the bipedicle flap for reconstruction of microtia is described. This technique makes possible construction of a well-shaped new auricle in the presence of scar formation because of tympanoplasty in which the external auditory canal has been created posteriorly. PMID- 4034766 TI - How to make superb microangiograms at reasonable X-ray exposures. AB - The technical factors in microangiography were studied, and we found that the main limiting factor in resolution was film grain size. Ultrafine grain films exist, but they are very slow, necessitating exposures of several hours at conventional settings. Using a modern beryllium window x-ray unit, equally good images can be made in 2 to 5 minutes by using the minimum tube-to-film distance (32 cm) and the maximum kilovoltage (110 kV). PMID- 4034767 TI - Muscle-transfer surgery. PMID- 4034768 TI - Nerve fiber planimetry in acute and chronic nerve lesions and in nerve lesions in continuity. AB - The level of resection of damaged nerve tissue in acute and chronic nerve lesions was determined on the basis of the vascular structure, the consistency of the nerve during palpation, the amount of interfascicular connective tissue, and the mushroom formation of the fascicles. Intraoperative electrophysiologic recordings were performed on the cut nerve ends to determine the function of the axons. Postoperative planimetric analyses of cross sections made through the resected nerve stumps were performed to measure axonal and endoneural tube diameters and to correlate these results with the clinical criteria used through the operating microscope. Axons in the proximal nerve ends of acute and chronic nerve lesions displayed a similar mean diameter. Endoneural tubes in chronic nerve lesions shrunk significantly as nerve repair was delayed. In several nerve lesions in continuity, axons remained present across the injured site despite absence of electrical conduction. When comparing the results of axonal or endoneural tube diameters of chronic nerve lesions to the results of other studies or acute nerve lesions, we demonstrated that careful examination through the operating microscope provided valid information about the proper management and resection level of chronic nerve lesions. Electrophysiologic evaluation aided the surgical management but was not useful for the resection of the distal damaged nerve segment. The presence of an evoked potential in the proximal nerve ends guaranteed a nearly normal nerve fiber diameter distribution, while the absence of such a potential in the distal nerve ends indicated an abnormal, absent, or disturbed endoneural tube diameter histogram. PMID- 4034769 TI - The early revascularization of membranous bone. AB - The experimental finding that membranous onlay bone grafts maintain volume and viability to a greater extent than do endochondral grafts may be related to the more rapid vascularization of membranous bone. Microangiographic techniques were used to study the rates of vascularization of membranous and endochondral bone grafts in adult white New Zealand rabbits at 1, 3, 7, 14, and 21 days after bone grafting. Vascularization patterns were quantified microscopically using a modified point-counting technique. At 3 days, membranous bone grafts demonstrated vessel ingrowth from both soft tissue and host bone. Little ingrowth was seen in endochondral grafts. By day 7, 2.5 vessels per square were identified entering membranous grafts, while an average of 0.6 vessels per square were counted for endochondral bone grafts. At day 14, there was an average of greater than 20 vessels per square for membranous grafts versus 1.8 for their endochondral counterparts. At 21 days, the endochondral grafts demonstrated persistent avascular central areas not seen in membranous grafts. Membranous onlay bone grafts in the rabbit are more rapidly vascularized than endochondral grafts. This factor may affect the greater volume maintenance seen in experimental membranous grafts. PMID- 4034770 TI - The treatment of periorbital infantile hemangioma with intralesional corticosteroid. AB - A series of 25 patients with periorbital hemangiomas was treated with intralesional corticosteroid injection. This resulted in a marked involution of the tumor in 16 patients, a moderate involution in 5 patients, and a minimal response in 4. No local or systemic complications were noted. The overall incidence of ocular complications in the form of amblyopia or strabismus secondary to the hemangiomas was 16 percent. PMID- 4034771 TI - Retroauricular island flap for eye socket reconstruction. AB - This paper describes the use of a flap which is the random portion of an island flap based on superficial temporal vessels. The flap has three distinct anatomic portions: the cutaneous portion, which includes the postauricular skin, the triangular deepithelialized scalp and fascia above the ear, which augments random pattern blood circulation to the cutaneous portion, and the superficial temporal fascia encompassing the vascular pedicle, which is dissected down to the upper pole of the parotid gland and unfolded using a cutback incision between the vascular pedicle and the second portion of the flap in order to increase the reach of the cutaneous portion. The flap has been successfully used in eight patients for reconstruction of missing or contracted eye sockets. In two patients, inconsequential superficial loss of the distal portion of the distal flap was observed. This flap can also be used for reconstruction of the external face, eyelid, and palate as well as soft-tissue augmentation. PMID- 4034772 TI - Isolated naso-ocular cleft: a one-stage repair. AB - The naso-ocular cleft is a rare defect; however, isolated alar clefts with or without additional hamartomatous local tissue are an even rarer problem. The authors describe six unilateral and one bilateral cleft patients who were all initially repaired using the same operative procedure. The concept of this procedure is based on the principle that there is basically no soft-tissue deficiency but rather a malpositioning of the parts. The leading edge of the ala is re-created by a rotation advancement of both the medial and the lateral segments adjacent to the cleft. The created secondary defect is filled with a paranasal transposition flap. Three of our patients had hamartomatous excesses and were the most difficult to balance, and at the same time, two of these patients required subsequent bridging or augmentation using a free conchal cartilage graft. Examples of the operative procedures are outlined both schematically and clinically. PMID- 4034773 TI - Total reconstruction of the "end-stage" cleft lip and palate deformity. AB - The purpose of this paper is to present a 5-year experience using a comprehensive surgical approach to reconstruct what we have chosen to call the "end-stage cleft lip and palate deformity." The deformity consists of varying degrees of midface retrusion, malocclusion, nasal deformity, and lip deformity. Most of the patients afflicted had unacceptable upper lip anatomy characterized by tightness and lack of cupid's bow and bulk. All had severe palatal scarring with resulting arch collapse and severe malocclusion. Most had had multiple surgical attempts to improve nasal aesthetics using standard rhinoplasty techniques with little or no improvement. The procedure involves splitting the upper lip with incisions extending into the upper buccal sulcus and rim of the nose allowing wide skeletalization of the maxilla and osteocartilagenous nasal skeleton. LeFort I or II maxillary advancement, nasal reconstruction, and upper lip modification (with Abbe flap if indicated) are done. The jaws are placed in intermaxillary fixation for 6 to 8 weeks. This comprehensive approach has been used in 16 patients, aged 15 to 29 years, with follow-up of up to 5 years. Excellent functional and aesthetic improvement has occurred in all patients, and complications have been minimal. PMID- 4034774 TI - Thermography as a predictive tool for laser treatment of port-wine stains. AB - The argon laser, which has been proven both useful and safe for port-wine stain therapy, interacts with the hemoglobin of the vessels. In a percentage of cases, this treatment is still inefficient, and there is a lack of correlation between these bad results and clinical or histologic criteria. Thermography, which explores the vascularization of the port-wine stain, leads us to consider port wine stains from a physical point of view. This very simple test shows no correlation with the clinical parameters of port-wine stain but is closely related to the results obtained with laser therapy. It seems to be a good criterion to estimate the argon laser treatment prognosis. PMID- 4034775 TI - Use of pectoralis minor muscle in immediate reconstruction of the breast. AB - A technique is described in which the pectoralis minor muscle is rotated as a muscle pedicle flap to be used in immediate reconstruction of the breast. The advantages of this procedure are that it provides additional muscle coverage over the prosthesis as well as preventing lateral displacement. Seven patients have undergone this technique with excellent results. PMID- 4034776 TI - Functional properties of palmaris longus muscles of rhesus monkeys transplanted as index finger flexors. AB - This experiment with skeletal muscle autografts in monkeys was designed to retest previous findings that transplanted skeletal muscle can regenerate to a functional degree in primates without predenervation and to test a new hypothesis that increased functional demands on regenerated muscle grafts in monkeys may result in improved functional capacity of the grafts. Rhesus monkey index flexors were replaced with free palmaris longus muscle autografts with microneural anastomoses between the graft motor nerve and the severed profundus motor nerve. One monkey was taught selective index flexion before grafting and continued with this program after grafting to test the effect of training on the graft. Mature grafts were evaluated for in vivo contractile properties and by histology and histochemistry and were compared with a group of normal Rhesus palmaris longus muscles. The results reconfirm the capacity of nonpredenervated monkey skeletal muscle grafts to regenerate and to achieve some contractile ability and suggest that training of free muscle grafts may enhance recovery of their functional and structural properties. PMID- 4034777 TI - Conservative and operative treatment of mallet finger. AB - One-hundred and thirty-five patients with mallet finger were treated and followed up at least 1 year after injury. Ninety-two patients with tendon rupture or chip fracture were treated by splinting, and 42 percent of them had a decreased range of motion, mostly of a minor degree, but only 18 percent stated complaints at the follow-up examination. The results of treatment in 43 patients with fracture were evaluated separately. In this group, 26 patients were operated on and the postoperative results were excellent in 58 percent, improved in 36 percent, and 8 percent ended with failure due to complications. Radiographic study showed bony union in 41 of 43 patients and resorption of the small fragment in 2 patients. The indications for conservative and operative treatment in the five different types of mallet finger are discussed. PMID- 4034779 TI - Communication in improving the work of the head and neck cancer team. PMID- 4034778 TI - Reduction of postischemic edema with hyperbaric oxygen. AB - In recent years, reports have shown positive effects of hyperbaric oxygen (HBO) treatment in posttraumatic circulatory insufficiency of the extremities. A tourniquet model for temporary ischemia was used to examine such treatment in rats. The circulation of the rat hindlimb was interrupted for 3 hours, while the contralateral uninjured leg served as control. There was a significant (p less than 0.001) postischemic edema in the tourniquet leg up to 48 hours after restoration of circulation. One group of animals received treatment with hyperbaric oxygen at 2.5 atmospheres absolute (ATA) for 45 minutes after release of the tourniquet. This significantly reduced (p less than 0.001) the postischemic edema, and the reduction persisted for 40 hours after the last treatment. It is concluded that hyperbaric oxygen reduces postischemic edema. Hyperbaric oxygen may therefore be useful as an adjuvant in the treatment of acute ischemic conditions when surgical repair alone fails or is not sufficient to reverse the ischemic process. PMID- 4034780 TI - One-stage lip-switch operation. AB - A one-stage lip-switch operation was successfully performed on an 80-year-old woman with accompanying disorders. Postoperative venous congestion was controlled mainly by dressing changes with wet gauze. PMID- 4034781 TI - The use of a free flap in homozygous sickle cell disease. AB - This paper describes what is thought to be the first reported use of a free flap in a patient with homozygous sickle cell disease. The utilization of a free flap in homozygous sickle cell disease should be questioned because the obligate period of ischemia to which the flap must be subjected during the transfer from donor to recipient sites might lead to intravascular sickling in the flap and flap failure. Review of the literature suggests that by reducing the level of sickle hemoglobin to the range of 25 to 40 percent, the risk of failure of a free flap is not significantly increased in the homozygous sickle cell patient. Furthermore, there is good evidence to suggest that a well-vascularized muscle flap provides optimal coverage, reversing the pathophysiologic cycle of the sickle cell ulcer. Thus in cases of multiply recurrent sickle cell ulcers in areas devoid of a local well-vascularized muscle flap, a free muscle flap is indicated, may be the procedure of choice, and can be performed successfully. We report a patient with a 4-year history of multiple recurrent sickle cell ulcers of the left ankle treated with a gracilis free flap. This patient has been followed for 2 years and continues to be free of recurrent ulceration. PMID- 4034782 TI - Replantation of the testis by microsurgical technique. AB - Microsurgical replantation of amputated testes were performed in two patients. Both were caused by trauma to the genitoperineal regions. These reconstructed testes are viable and not atrophic grossly. The patients are satisfied with these operations. PMID- 4034783 TI - Massive scrotal edema as a complication of abdominoplasty. AB - Massive scrotal edema is an unreported complication of abdominoplasty. This patient's postoperative decompensation of medial thigh and scrotal lymphatic return may well have been due to an occult lymphedema tarda or previously compromised lymphatics from the fibrosis of venous stasis disease and obesity. PMID- 4034785 TI - The pixie earlobe: a method of correction. AB - A simple method for the correction of the pixie earlobe is documented. This technique preserves the natural free border of the earlobe. PMID- 4034784 TI - Care of pentamadine ulcers in AIDS patients. AB - Two cases of soft-tissue infection resulting from antibiotic therapy given AIDS patients are presented. Operative treatment resulted in a closed wound in one patient. In the other patient, who suffered from recurrent acute illnesses, nonoperative treatment resulted in slow wound contraction and epithelialization without secondary wound complications. Wound sepsis did not occur, despite the absence of normal immune function. Operation and additional hospitalization, with their attendant risks, were avoided. PMID- 4034786 TI - The harvesting of cranial bone grafts: a guided osteotome. AB - A technique for in situ harvesting of the outer table of the skull using a "guided" osteotome is presented. While guards have been placed to control the depth of the blade, additional steps are advised to ensure the highest level of safety in clinical use: Before harvesting the graft, a full set of anteroposterior and lateral x-rays should be examined to determine which areas of the skull are thin and should be avoided. All areas with cranial sutures should be avoided because here the dura is more firmly attached to the inner table making perforation more dangerous. Bone should not be harvested under the hairless forehead region because this results in a visible depression. The surgeon should use the guards as guides to visually monitor the depth of the blade. The surgeon should not attempt the procedure without having a set of three different depths (1 mm, 2 mm, and 3 mm) available. Different skulls have different thicknesses of the outer table, and the technique loses the advantage of safety if an inappropriate depth is used. PMID- 4034788 TI - Internal fixation of bone by screws. PMID- 4034787 TI - Gillies, or patiala combined needle holder? PMID- 4034789 TI - Rhabdomyosarcoma of the orbit. PMID- 4034790 TI - Pectoralis minor for facial palsy. PMID- 4034791 TI - Minimizing blood loss in reduction mammaplasty. PMID- 4034792 TI - Marjolin's ulcer was not Marjolin's. PMID- 4034793 TI - [3 autopsy cases of adult pigment type (Peiffer) of familial sudanophilic leukodystrophy]. PMID- 4034794 TI - [Symposium: psychiatric education]. PMID- 4034795 TI - A methodology for studying similarities and differences in educational priorities across national lines. PMID- 4034796 TI - [Effects of prolonged methamphetamine treatment and its withdrawal on behavior and brain monoamine metabolism in mice]. PMID- 4034797 TI - [A case of periodic lateralized epileptiform discharges]. PMID- 4034798 TI - [Clinicogenetic studies within the scope of Leonhard taxonomy]. AB - Using conventional genealogical methods and genetic correlation analysis, the author investigates Leonhard's classification of schizophrenias and cycloid psychoses. According to the second of these methods, the systematic schizophrenias and cycloid psychoses definitely diverge on account of the phenotypic correlations, whereas the unsystematic group presumably occupies a median genetic position between the two categories first mentioned. PMID- 4034799 TI - [Some ethical aspects of psychotherapeutic work]. AB - A few thoughts are presented regarding the current discussion concerning ethical aspects of psychotherapy in socialist society. The author states his opinion regarding such problems as the obligation to take maximum care, the obligation to be constantly on call, professional discretion, the obligation to give treatment, cooperation with colleagues and the necessity of self-experience for the psychotherapeutic on the basis of experience gained in psychotherapeutic practice. PMID- 4034800 TI - [Acrocephalosyndactylia--Vogt syndrome]. AB - A genetically remarkable case of the Vogt syndrome (combination of the Apert and Crouzon syndromes) associated with a dysraphia syndrome is described. Clinically, malformations corresponding to the Apert syndrome were prominent, and radiological examination of the skull revealed a prominent Crouzon syndrome. Investigation of the familial background revealed the presence of malformations in other members of the family, such as malformation of the extremities and acrocephalus. On the other hand, the father's age of 63 years was considerably higher than that of fathers in the average population, so that the possibility of a new mutation had to be considered. The fact that the mother suffered an attack of influenza during pregnancy, finally, brought the possibility of peristatic influences being involved in the complex malformations. PMID- 4034801 TI - [Frequency of the P3 component of the acoustic ERP in children with normal or diminished concentration ability]. AB - The occurrence of the P3 component of the acoustic vertex ERP after an appropriate stimulus was recorded for 27 male children (including 6 with early brain damage) with normal and 37 (including 33 with early brain damage) with below-normal concentration. Both groups had the same mean age and intelligence. A P3 component was found in the case of 18 subjects with normal and 9 with below normal concentration. The rearrangement of the subjects to give one group with, and one without, brain damage yielded smaller differences. The significant difference (p less than 1%) in the frequencies with which the P3 component occurred, taking the mean concentration into account, leads to the assumption that the internal processing of the stimulus is disturbed in boys with poor concentration. PMID- 4034802 TI - [Experiences with the combination of communication training and dynamic group psychotherapy]. AB - Three psychotherapy groups consisting of altogether 37 patients took part in communication training after L. Schabisch and M. Sieme in preparation for group centred dynamic psychotherapy. The results of pretherapy and post-therapy surveys with the MMPI were tested for quantitative changes using Posthoff and H. F. Bottcher's gnoseologically based test. The findings suggest that this combination of methods has a high standard of efficiency, which is finally discussed. PMID- 4034803 TI - [Receptive individual music therapy in the concept of ambulatory psychotherapy]. AB - Practical experience regarding the application of receptive individual music therapy after Schwabe is used as a basis to discuss its use at outpatient surgeries. The method is used for patient-centred psychodynamic counselling of neurotics and can, because it permits particularly an emotional access to the patient, accelerate the treatment. The author discusses the treatment itself, its indicants, the training of therapeutics, questions of medical competence and the constraints limiting its application for outpatient treatment. PMID- 4034804 TI - [Practice-relevant problems of psychodiagnostically oriented dispensary models]. AB - Dispensary care covers all efforts directed towards maintaining health in the sense of physical, mental and social well-being. In view of the purely organ related standpoint, which is still sometimes encountered, problems may arise in practice which obstruct endeavours towards this aim. Screening was used to identify, among groups with levels of psychoneurological stress higher than the mean yielded by epidemiological surveys and which increase with increasing length of vocational life, subjects whose neurotic symptoms predominated among the totality of pathological findings. Possible conclusions are drawn for the further implementation of an optimized dispensary strategy at the basis. PMID- 4034805 TI - [Forensic activity and scientific research]. PMID- 4034806 TI - [Psychiatric hospitals--an institutionalized defense system. I]. AB - In the early beginnings of the constructional phase of a "sociopsychiatric satellite" of a rural psychiatric hospital where classical treatment parameters had been abandoned, signs were seen of trends towards a severely pathological group process which threatened to draw--induced by the patients--even the psychiatric attendants, nurses, helpers and physicians into the maelstrom of a mad interlock. At first, the sequence of events leading to this fateful climax remained largely below the threshold of consciousness. It became manifest by counter-transference reactions on the part of the psychiatric coworkers and generated creative powers which went beyond the processes described in literature in so far as they aimed at encompassing and sweeping along the institution as a whole. This prompts the author to suspect that the part played by the patients in the creation, shaping and routine reproduction of the institution known as "psychiatric hospital", has been underestimated up to now. After supplementary descriptions of the mutual involvement process in Part II, an attempt is made, in analogy to the concept of Mentzos, to describe the defence moves against such a pathological symbiosis as an essential part of psychiatric treatment institutions, especially of psychiatric hospitals or "asylums". PMID- 4034807 TI - [The origin of violence in psychiatry--a contribution to double-bind rage]. AB - The discussion about Euthanasia newly has raised the question on the violent implications of interaction in psychiatry. Psychiatry is under obligation of the forces of order on one, of the wish to help on the other side. This double bind reflects an interactional feature of construction which the psychotic patient has to go through, but which he carries on too. The selfreduplicative construction of originally individual double bind-situations corresponds to the patient's conception of live, but evokes a specific, only perceptible at short notice, disintigrating "double-bind-Wut" in the involved therapist, which mainly is endangering the patient. The state of "double-bind-Wut" and the working up of this rage is determined by the primary process therefore directly unconscious. We investigate to what extent the "double-bind-Wut" is to make perceptible and thus to handle; by the means of casuistic microstructures we give reasons for the assumption that the desintrating power of "double-bind-Wut" might become a methodical paradigm of future research. PMID- 4034808 TI - [Liberal or controlled approach--the management of violent patients in psychiatric clinics]. AB - The traditional mental hospitals are said to hamper recovery and obstruct rehabilitation by an authoritarian therapeutic regimen. Nevertheless, the claim of community-oriented hospitals that a liberal therapeutic style improves prognosis and makes treatment more human requires scrutiny. The management of violent patients who call for controlling and disciplinary measures seems to be crucial. In the light of a case-history the article describes, how a misinterpretation of liberal principles complicates the treatment of dangerous patients and supports an attitude which does not admit the double character of psychiatric therapy in regard of the inevitable conflict between safety precautions and therapeutic engagement. PMID- 4034809 TI - [Italian psychiatry reform in the Piedmont region: Law no. 180 and its consequences]. AB - Psychiatric reform in the northern Italian region of Piedmont following Law No. 180 is described. From 1977 to 1981 the overall psychiatric hospital inmate population is reduced from 5.544 to 2.396, the majority of patients discharged is now living in outpatient therapeutic communities, private psychiatric hostels and nursing homes. 76 community mental health centres with an average catchment area of 59.000 inhabitants and a medium of 250 patients as well as 21 psychiatric wards in general hospitals with a total of 253 beds are set up to substitute psychiatric hospitals. Inpatient admission and discharge numbers are stable in the years preceding and following law no. 180, private psychiatric hospitals decrease their proportion of total admission numbers from 49% (1975) to 40% (1980). Percentage of compulsory inpatient treatments falls from 30% (1975) to 6% (1980), duration of hospital treatment is drastically reduced. There is an integration of psychiatric services in the general health care system, utopic reform objectives have not been reached. PMID- 4034810 TI - Brief psychotherapy with vulnerable patients: an outcome assessment. AB - The outcome of brief therapy with psychologically vulnerable patients is uncertain, and some clinicians, anticipating negative effects, recommend exclusion of such patients from time-limited treatment. We had the opportunity to explore the results of time-limited dynamic therapy with eight vulnerable patients, a subsample within a larger series of 35 persons treated for pathological grief reactions precipitated by parental death. These cases included three poor outcomes, four good outcomes, and one fair outcome. Examination of each case individually suggests that for the majority, brief therapy was useful in stemming a downhill course. In some cases, it also provided a bridge to an indicated longer-term psychotherapy. PMID- 4034811 TI - Splitting dynamics, self-representations and boundary phenomena in the group psychotherapy of borderline personality disorders. PMID- 4034812 TI - Pills as transitional objects: a dynamic understanding of the use of medication in psychotherapy. AB - Combining psychotherapy with psychopharmacology is a clinically challenging endeavor. In the psychopharmacology of the borderline patient, pills may function as transitional objects. This point is derived from a review of the literature, and illustrated by clinical material from three case studies. Recognition of the transitional properties of pills may aid therapists in making sense of many clinical phenomena and in developing effective treatment strategies. Other psychodynamic concepts may be useful in understanding the complex integration of psychotherapy and psychopharmacology. PMID- 4034813 TI - From conflict to collaboration: psychiatry and the hospital police. AB - Social control is one of the major tasks of the profession of psychiatry (Astrachan, Levinson, and Adler 1976; Adler, Astrachan, and Levinson 1981). The reduction and control of deviant behavior in the community, in the hospital, and on the psychiatric ward are essential, if underappreciated, responsibilities which psychiatrists must negotiate every day. In large urban general hospitals, an increasingly common site for psychiatric programs, deviant behavior derives both from the psychopathology of the patients and from the intrusion of criminal influences from the community. Many urban hospitals have an institutional police force that, like the psychiatry service, is charged with responsibility for managing deviant behavior, albeit through law enforcement methods rather than clinical ones. In recent years law enforcement officers and psychiatrists have increasingly become involved with each other in areas where their social control responsibilities overlap. This increased involvement has often been accompanied by tension, distrust, and, at times, overt antagonism between the two groups. This paper will describe and analyze fundamental sources of this tension and outline one approach to its reduction. PMID- 4034814 TI - Interpersonal behavior and therapeutic progress: therapists and clients rate themselves and each other. AB - To measure the extent to which progress in psychotherapy can be predicted from the interpersonal styles of therapists and clients, 42 outpatients and their 11 therapists rated themselves and each other on Benjamin's Structural Analysis of Social Behavior (SASB) scales. In addition, therapists rated amount of client change and therapy success-failure, based on the outcome section of the Rogers and Dymond (1954) scale, and clients used the Strupp, Fox, and Lessler (1969) questionnaire to evaluate progress-to-date. Clients also completed the Hopkins Symptom Checklist (HSCL) at the start of therapy and after they had completed at least 6 treatment sessions. Canonical analyses indicated that when optimally weighted, SASB scores can predict at least 65% of the reported progress variance, lending credence to claims that "reflexive social behavior" and "the relationship" are important determinants of certain aspects of therapeutic outcome. Consistent with previous literature, clients reported more satisfaction with therapy when they perceived their therapists as "warm and freeing," but such perceptions were not systematically related to reported symptom reduction. Unfavorable self-concept ratings by therapists and therapist ratings of clients as "helping or protecting," which suggest role reversal, were negatively associated with symptom amelioration. PMID- 4034815 TI - Failing to resist hypnotic test suggestions: a strategy for self-presenting as deeply hypnotized. AB - Traditionally, hypnosis has been associated with the idea that highly hypnotizable subjects lose voluntary control over their responses and become incapable of resisting suggestions. We contend instead that even excellent hypnotic subjects retain control over their responses. These subjects are invested in presenting themselves as "deeply hypnotized," and to this end employ relevant contextual information to guide their hypnotic enactments. Contextual demands in the hypnotic test situation usually reinforce the idea that hypnotic behavior is involuntary. Therefore, the enactments of highly hypnotizable subjects are typically designed to convey the impression that responses to suggestions are involuntary happenings that cannot be successfully resisted. This formulation implies that highly hypnotizable subjects will present themselves as unable to resist suggestions or, alternatively, as able to easily resist suggestions, depending upon which of these self-presentations they associate with "deep hypnosis." We tested this and related hypotheses by varying the demands associated with "deep hypnosis" and noting the effects on the tendencies of highly hypnotizable subjects to resist suggestions and to describe their responses as involuntary happenings over which they had lost control. PMID- 4034816 TI - Cigarette brand switching: relating assessment strategies to the critical issues. PMID- 4034817 TI - Detection theory analysis of group data: estimating sensitivity from average hit and false-alarm rates. PMID- 4034818 TI - Quantitative models of the genetic transmission of schizophrenia. PMID- 4034819 TI - Information processing rates in the elderly. PMID- 4034820 TI - Myths about male midlife crises. PMID- 4034821 TI - An empirical investigation of mood characteristics of highly apprehensive persons. PMID- 4034822 TI - Influence of age and body proportions on weight loss of obese women after treatment. PMID- 4034823 TI - Modification of pain through covert positive reinforcement. PMID- 4034824 TI - Criterion-related validity of the Kansas Marital Satisfaction Scale. PMID- 4034825 TI - Locus of control and perceived stress among student-teachers. PMID- 4034826 TI - Assessment measures that discriminate between levels of DUI clients. PMID- 4034827 TI - Reliability and discriminant validity of the children's drug-use survey. PMID- 4034828 TI - Reexamining the Beck Depression Inventory: the long and short of it. PMID- 4034829 TI - Comparisons of psychiatric outpatients with controls on Bipolar Profile of Mood States. PMID- 4034830 TI - WISC and WISC-R range and mean deviation: indices of scatter for a clinic referred population. PMID- 4034831 TI - Helping Beliefs Inventory: brief screening measure for training volunteer applicants in counseling. PMID- 4034832 TI - Rated clinical utility of the Psychological Inventory of Personality and Symptoms. PMID- 4034833 TI - Test-retest Wechsler Intelligence Scale for Children-Revised scores for 310 educable mentally retarded and specific learning disabled students. PMID- 4034834 TI - Efficiency points: total score versus subject area score--is there an association? PMID- 4034835 TI - Comment on Belden, Braukmann, and Wolf. PMID- 4034836 TI - Depression and fear of death in a normal population. PMID- 4034837 TI - Biases in betting: an application of laboratory findings. PMID- 4034838 TI - Perceptions of community carers about elderly people: a sentence completion approach. PMID- 4034839 TI - Unconscious content. PMID- 4034841 TI - General and physical self-esteem and altruistic behavior. PMID- 4034840 TI - Concordance ratings of community adjustment for older psychiatric inpatients. PMID- 4034842 TI - Adjustment of Vietnamese refugee youths: a self-report. PMID- 4034843 TI - Evaluation of a multimodal structured group approach in treatment of depression. PMID- 4034844 TI - The effects of noise on the processing of global shape and local detail. PMID- 4034845 TI - Continuous information processing in conceptual identifications. PMID- 4034847 TI - The Morinaga misalignment effect: reduction and reversal by modification of figural extremities. PMID- 4034848 TI - Social influences on conditioned cortisol secretion in the squirrel monkey. AB - 'Social buffering'--the apparent capacity of group membership to reduce the adrenocortical response to stress, was investigated in squirrel monkeys by means of a between-within experimental design. Adult males were assigned to two groups. Group paired (n = 6) received pairings of a conditional stimulus (CS) with footshock. Group control (n = 6) received CS presentations without shock. All animals were then tested with 10 presentations of the CS without shock under three social-housing conditions, in four successive phases of the experiment: individual, dyad, group, and individual housing. Neither group showed a cortisol response to the CS prior to training. Following training, CS-evoked elevations of cortisol were found only in group paired, and only in the individual housing conditions. These results replicate and extend our previous finding that the presence of conspecifics can ameliorate a neuroendocrine response to psychological stressors in squirrel monkeys. PMID- 4034849 TI - Vasopressin--oxytocin in cerebrospinal fluid of schizophrenic patients and normal controls. AB - Vasopressin and oxytocin seem to be involved in the processes of learning and memory in animals and probably in man. These peptides appear to have opposite effects in that vasopressin improves memory processes and oxytocin produces amnestic effects. We measured these neuropeptides in the cerebrospinal fluid of schizophrenic patients with and without neuroleptic treatment, psychiatrically healthy controls and drug-free patients before and after three weeks' neuroleptic treatment. There were no significant differences in vasopressin concentrations between schizophrenics and controls. No influence of neuroleptic treatment on vasopressin concentrations was detected. In contrast, concentrations of oxytocin were increased in all schizophrenic patients and were higher in those receiving neuroleptic treatment. In addition, oxytocin concentrations increased after three weeks' neuroleptic treatment. Drug-induced increase of oxytocin concentrations may be of significance in the clinically observed amnestic syndromes and debilitation in schizophrenics treated with neuroleptics. PMID- 4034850 TI - Differential responses in prolactin levels induced by naloxone in humans. AB - The plasma prolactin (PRL) response to the opiate antagonist naloxone was tested in drug-free healthy volunteers (10 men, 18 regularly menstruating women who were in the late follicular phase of their ovarian cycles, and seven post-menopausal women). Naloxone hydrochloride (2 mg intravenous bolus) and placebo (normal saline) were administered on two different days in a double-blind fashion. Blood samples were collected at -15, 0, 30, 60, 120, 180 and 240 min after the injection. In the women of reproductive age, naloxone reduced plasma PRL concentrations, whereas in the post-menopausal women and the men, naloxone resulted in no significant change. However, in the post-menopausal women treated with estrogen (intramuscular 17-beta-estradiol), the opiate antagonist was able to lower plasma PRL concentrations. Thus, it appears that opiate effects on PRL secretion are influenced by the gonadal steroid environment and that estrogens may play a modulating role. PMID- 4034846 TI - Conditioned taste aversion and traditional learning. PMID- 4034851 TI - Diagnostic performance of the thirty-four hour dexamethasone suppression test. AB - The performance of the dexamethasone suppression test (DST) in the diagnostic confirmation of endogenous depression was compared according to two times of blood collection--1600 hr on day 2 (usual sample) and 0800 hr on day 3 (34 hr after dexamethasone intake)--in 14 endogenous depressives and in a control group of 17 psychiatric inpatients with other diagnoses. For the day 2 (1600 hr) sample, a 5 micrograms/dl cortisol concentration represented the best cut-off score, with sensitivity of 57% specificity of 88%, and diagnostic confidence of 80%. For the day 3 (0800 hr) sample, the best cut-off score was 20 micrograms/dl, with the same sensitivity (57%) but there was a decrease of both specificity (to 76%) and diagnostic confidence (to 67%). The mean cortisol levels were much higher on day 3 than on day 2, suggesting that the inhibitory activity of dexamethasone was no longer present. PMID- 4034852 TI - Treating phase typed chronobiologic sleep and mood disorders using appropriately timed bright artificial light. PMID- 4034854 TI - CSF, plasma, and urine: what do concomitant measurements of norepinephrine and its metabolites mean? PMID- 4034853 TI - Serotonergic modulation of cortical rat noradrenergic system in the mechanism of action of antidepressant drugs. PMID- 4034855 TI - Neuropeptidergic regulation of feeding. PMID- 4034856 TI - Peptide-catecholamine interaction: feeding and satiety. PMID- 4034857 TI - Isoproterenol-induced anxiety states. PMID- 4034858 TI - The lactate infusion model. PMID- 4034859 TI - Serotonin-behavior interactions in vervet monkeys. PMID- 4034861 TI - Depression, hypothalamic-pituitary-adrenocortical activity, and lymphocyte function. PMID- 4034862 TI - Psychobiological markers for schizophrenia: state of the art and future perspectives. PMID- 4034860 TI - The alpha MSH-specific and arcuate pro-opiomelanocortin neuronal systems of the hypothalamus: observations on their connectivity and response to colchicine treatment. PMID- 4034863 TI - Are there state-dependent markers in schizophrenia? PMID- 4034864 TI - Vulnerability to schizophrenia: childhood indicators predict adult outcome. PMID- 4034865 TI - Distractibility as a marker of vulnerability to schizophrenia. PMID- 4034866 TI - Neurophysiological aspects of information processing in schizophrenia. PMID- 4034867 TI - Sensory and perceptual behavioral markers of schizophrenia. PMID- 4034868 TI - Cholecystokinin potentiates dopamine-mediated behaviors in the nucleus accumbens, a site of CCK-DA co-existence. PMID- 4034869 TI - Persistent effects of amphetamine, p-chloroamphetamine, and related compounds on central dopamine and serotonin neurons in rodents. PMID- 4034870 TI - The epidemiology of anxiety disorders: a highlight of recent evidence. PMID- 4034871 TI - Major depression and panic disorder: a family study perspective. PMID- 4034872 TI - Panic disorder and major depression: biological relationships. PMID- 4034873 TI - Lactate infusion in patients with depression and anxiety. PMID- 4034874 TI - Effect of panic attacks on the treatment of atypical depressives. PMID- 4034875 TI - Hormones and depression--conceptual transitions. PMID- 4034876 TI - Magnetic resonance imaging studies of schizophrenia. PMID- 4034877 TI - Dopamine receptor binding of C-11-3-N-methylspiperone in the caudate in schizophrenia and bipolar disorder: a preliminary report. PMID- 4034878 TI - Behavioral treatment of social phobia. PMID- 4034879 TI - Molecular basis of drug-resistance mutations in C. elegans. PMID- 4034880 TI - Biophysical alterations in cell membranes associated with psychotherapeutic drug exposure, psychopathology, and aging. PMID- 4034881 TI - Adrenergic agonist therapy in alcohol withdrawal states in man. PMID- 4034882 TI - Chemical approaches to drug delivery to the central nervous system. PMID- 4034883 TI - Implantable narcotic antagonists: a possible new treatment for narcotic addiction. PMID- 4034884 TI - Depression in adults with a history of prenatal DES exposure. PMID- 4034885 TI - Cortisol and prolactin responses to dexamethasone in major depression, chronic pain, and chronic pain with major depression. PMID- 4034886 TI - Evidence for a daily rhythm of plasma HVA in normal controls but not in schizophrenic patients. PMID- 4034887 TI - Addition of estrogen to imipramine in female-resistant depressives. PMID- 4034888 TI - The stress-alexithymia hypothesis: theorectical and empirical considerations. AB - An association has been noted between the presence of alexithymic characteristics and psychosomatic/stress-related illness. A hypothesis is presented here outlining the mechanisms through which stress and alexithymic characteristics contribute to the development of stress-related illness. This hypothesis, the stress-alexithymia hypothesis, is considered here in the context of stress research from both theoretical and empirical perspectives. From these considerations, it appears that the stress-alexithymia hypothesis does have a theoretical basis. Additionally, there is indirect empirical evidence supporting the proposed influence of alexithymic characteristics on the physiological stress response. It is suggested that future research should directly examine the influence of alexithymic characteristics on stress responding and use alexithymic characteristics heuristically to explore the role of affect in the illness process. PMID- 4034889 TI - The role of anger in hypertension. AB - We report a study about the administration of two Dutch questionnaires (the State Trait Anger Scale and the State-Trait Anxiety Inventory) to a sample of patients with essential hypertension and to a matched control group. Analyses of the test results demonstrated that some significant differences could be observed in the levels of anxiety and anger. Special attention was paid to certain test-item answers, showing that hypertensives, although feeling irritated and angry, retreat to some extent from showing their anger. PMID- 4034890 TI - The medical-psychiatric unit: a novel psychosomatic approach. AB - A retrospective chart review of 600 general hospital patients, of whom 200 had been admitted to a medical-psychiatric unit, 200 to a conventional psychiatric unit and 200 to medical-surgical units, and for whom psychiatric consultation had been requested, disclosed significant differences in the patient populations of these services. The data suggest that consultation psychiatry and medical psychiatric units serve two different subgroups of patients with combined physical and psychiatric illness. A comprehensive model of clinical psychosomatic medicine encompassing consultation psychiatry, liaison psychiatry, medical psychiatric units and after-care medical-psychiatric clinics, is proposed. PMID- 4034891 TI - Alexithymia and the split brain. I. Lexical-level content analysis. AB - 8 cerebral commissurotomy patients and 8 precision-matched normal control subjects were shown a 3-minute videotaped film symbolically depicting the deaths of a baby and of a boy. After each of 4 showings, all subjects were questioned about the symbolic and emotional contents of the film. Content analyses of the subjects' spoken and written responses were carried out on the lexical level. The commissurotomized patients, in comparison to their normal controls, used a lower percentage of affect-laden words, had a higher percentage of incomplete sentences, used a higher percentage of auxiliary verbs, and used a lower percentage of adjectives. Commissurotomy patients were significantly closer to the alexithymic pole of a factor derived from these 4 variables. PMID- 4034892 TI - Coping behaviors of severe diabetics. AB - In order to study the relationship between personality and the development of diabetic retinopathy in patients with diabetes mellitus, diabetics with retinopathy (severe group) and sex-, age-, and duration-matched diabetics without complications were tested by psychological tests, and interviewed. The result of the Yatabe-Guilford personality test (Y-G) and Spielberger's State and Trait Anxiety Inventory revealed that subjects were emotionally and socially stable and well-adjusted types and less anxious in the severe group than in the mild group. The interview findings reveal that the severe group had neglected the medical treatment and the diet therapy for significantly longer periods of time and the incidence of a childhood parental separation was significantly higher in the severe group than in the mild group. Discussion focuses on the severe diabetics' coping behavior which is characterized by the neglect of medical treatment and diet therapy for extended periods of time, which in turn resulted in diabetic retinopathy and other complications. Such coping behavior is shown to be equivalent to that found in the alexithymic behavioral syndrome. PMID- 4034893 TI - [Social psychology in depth psychology and analytic psychotherapy]. PMID- 4034894 TI - [Psychoanalytic interactional therapy]. PMID- 4034895 TI - [Psychosomatic consultation in a large clinic: problems of integration and patient compliance]. PMID- 4034896 TI - [Value concepts of psychotherapists, candidates and students]. PMID- 4034897 TI - [Competitive sports in psychoses]. PMID- 4034898 TI - [Psychosomatic day clinic: last experience?]. PMID- 4034899 TI - [Is the success of psychotherapeutic treatment predictable? Experiences from the Penn Psychotherapy Project]. PMID- 4034900 TI - [Reflections on the evaluation of psychotherapeutic treatments]. PMID- 4034901 TI - [Phobic organ neuroses]. PMID- 4034902 TI - [Behavior therapy with groups of normal-weight essential hypertension patients in general practice]. PMID- 4034903 TI - Recent developments in the classification of pain. PMID- 4034904 TI - Clarity of request for consultation: its relationship to psychiatric diagnosis. PMID- 4034905 TI - Patients' reactions to house staff work rounds. PMID- 4034906 TI - Barrett's syndrome presenting as globus hystericus. PMID- 4034907 TI - Behavioral instruction for a patient's relative to increase antihypertensive compliance. PMID- 4034908 TI - Vaccination against measles and other viral diseases. PMID- 4034909 TI - Sanatorium admissions in a boys' boarding school. PMID- 4034910 TI - Childhood accidents: a registration in public and private medical facilities of a French health care area. PMID- 4034911 TI - Measles outbreak in a day nursery. PMID- 4034912 TI - Comparison of occupations recorded at cancer registration and death. PMID- 4034913 TI - An audit of antibiotic prescribing in general practice using sore throats as a tracer for quality control. PMID- 4034914 TI - Undergraduate attitudes to exposure to an NHS resource allocation problem. PMID- 4034915 TI - Fluid compartmentation and articular mechanoreceptor discharge in the cat knee joint. AB - Experiments were performed to determine the effect of alteration of intra articular pressure in different areas of the cat knee joint on the discharge of slowly adapting mechanoreceptors in the posterior region of the joint. At physiological (subatmospheric) pressures the anterior and posterior regions of the knee joint are not hydraulically continuous. However, at supra-atmospheric pressures between 2.5 and 9 cmH2O there is free communication between these areas. The discharge of receptors in the posterior region of the joint is influenced by intra-articular pressure changes in the posterior region when these are supra-atmospheric. However, pressure changes in the anterior region of the joint have little effect on the discharge of these receptors until free communication occurs between anterior and posterior regions. It is suggested that articular mechanoreceptors detect tension changes in collagen fibrils rather than volume changes of the joint capsule. PMID- 4034916 TI - The response of slowly adapting mechanoreceptors in the cat knee joint to tetanic contraction of hind limb muscles. AB - The effect of tetanic contraction of muscles acting at the cat knee joint on the discharge of various types of slowly adapting knee joint receptors was investigated. Contraction of a particular muscle could either increase, decrease or produce no alteration in the discharge of a given receptor. Whatever effects were produced by muscle contraction, these effects were always maximal at extremes of the flexion/extension range, and enhanced by limb movement. However, these receptors could not be induced to discharge at intermediate positions either by the passive tension or active contraction of muscles around the knee joint. It is concluded that muscle contraction does not increase the proportion of joint receptors (approximately 18%) which are known to spontaneously discharge at intermediate positions in the absence of significant muscle tone (Ferrell, 1980). PMID- 4034917 TI - Milk accumulation and secretion in the rabbit. AB - Over the 24 h period after suckling, total mammary-gland weight increased linearly indicating no reduction in the rate of milk secretion during the relatively long interval between sucklings in the rabbit. Thus, storage capacity is matched to the long storage period. Beyond 24 h in the absence of suckling at 24 h, the rate of milk accumulation declined rapidly. This decline was not prevented by the administration of ovine prolactin or by permitting suckling of sealed teats at 24 h. During the decline in secretory rate after 24 h, milk [Na] and [Cl] increased while [K] and [lactose] decreased, as in other species. It is concluded that the decrease in secretory rate after cessation of suckling is not caused by lack of hormonal stimulation; it is suggested that mammary distension caused by accumulation of milk is responsible. PMID- 4034918 TI - Synaptic arrangements formed by serotonin-immunoreactive axons in the substantia gelatinosa of the rat spinal cord. AB - Ultrastructural properties of serotonin-immunoreactive axons in the rat's substantia gelatinosa were examined in order to determine the synaptic arrangements that they form in the neuropil. Some immunoreactive varicosities formed synaptic associations with somata or dendrites suggesting that serotoninergic systems are capable of influencing the activity of these structures post-synaptically. No examples of axo-axonic synapses were found. Most varicosities, however, did not form identifiable synaptic junctions, but were closely associated with somata, dendrites or axons. Some of these associations may be functional but morphological evidence for this is lacking. PMID- 4034919 TI - Effects of water availability on plasma protein and sodium concentration, haematocrit and plasma osmolality in the pig. AB - Eighteen young growing pigs of the Large White breed were housed in individual pens or metabolism stands and habituated to drinking their water from a bowl. Those housed in the metabolism stands were surgically fitted with a catheter placed in he jugular vein to allow collection of blood samples. The voluntary intake of water after periods of progressively increasing water deprivation was measured. The measurements were made by allowing the pigs to drink to satiety after either a 2, 4, 8, 12 or 18 h period of water deprivation. Voluntary water intake was a function of the duration of water withdrawal and the rate of intake increased with progressive deprivation. Changes in plasma concentration of sodium and protein, haematocrit and osmolality could be detected after 12 and 18 h of dehydration. The progressive changes in plasma sodium concentration ([Na+]), osmolality, protein concentration and haematocrit during adaptation to dehydration when water was withheld for 72 h were examined in six pigs. Using a technique of continuous blood sampling, the rapid changes in the same blood parameters during rehydration, when water was made freely available at the end of the 72 h period, were also monitored. The [Na+] and osmolality dropped precipitously following the onset of drinking. From the 15 min stage to the 4 h stage with water available ad libitum, the values of both parameters remained below their control levels. However, the plasma protein concentration and the haematocrit values remained significantly above their pre-dehydration control levels up to the 4 h stage, even with water freely available, thus showing that drinking stopped even though the extracellular fluid phase remained dehydrated. Only with food available did the blood measures return to normal. It is concluded that the cellular fluid phase forms an integral part of the mechanisms involved in the termination of drinking in the pig. PMID- 4034920 TI - Osmotic and ionic regulation during dehydration in a large bird, the emu (Dromaius novaehollandiae): an important role for the cloaca-rectum. AB - The emu, a large (40 kg) flightless bird, has low water requirements yet it has a limited ability to produce concentrated urine. To clarify the factors involved in excretion and water conservation by the emu the patterns of excretion during water restriction were examined. Additionally, kidney function was studied, as also was the role of the cloaca and rectum in the final modification of excreta. Following water restriction the osmolality of the excreta fluid increased to a maximum level at 6 d of 428 +/- 39(8) mosmol (mean +/- S.E.M. (n)), the urine to plasma ratio being 1.35 +/- 0.12(8). In normally hydrated birds almost all Na and Cl were excreted in the fluid fraction but a third of the K was associated with the solid fraction of the excreta. After water restriction for 9 d the pattern of excretion of K did not change but the majority of Na (79%) and Cl (73%) were excreted in the solid phase, possibly associated with urates. In ureteral urine most of the nitrogen was excreted as uric acid or urates; a large fraction, 36 +/ 4(4)%, was not identified. The glomerular filtration rate (G.F.R.) was 41.3 +/- 2.2(6) ml/kg.h. This value is low when compared with other birds and may be related to the large size of the emu. The G.F.R. decreased by 30% after 7 d water restriction. The cloaca-rectum appears to play a major role in the modification of excreta. In vivo perfusion studies showed transepithelial net transport rates of water and major electrolytes to be large. Transport of water from an isosmotic solution, 3.36 +/- 0.17 ml/kg.h, was approximately 10 times the maximum value reported for birds previously. The Na and Cl transport rates were also comparatively high. PMID- 4034921 TI - The dependence of the relaxation of tension of frog atrial-trabeculae on the sodium-calcium exchange: a voltage-clamp study. AB - The dependence of the relaxation of tension of isolated frog atrial trabeculae, upon membrane potential, [Na]0 and [Ca]0, has been studied under voltage-clamp conditions. The change in tension following the repolarization of the membrane potential can be resolved into two phases: an initial phase which opposes relaxation and has an exponential time constant of about 80 ms and is unaffected by changes in either membrane potential, [Na]o or [Ca]o; and a subsequent exponential fall in tension, the rate of which is slowed by depolarization, raised [Ca]o or lowered [Na]o. The dependence of the second phase of relaxation upon the membrane potential is consistent with Ca2+ being removed from the sarcoplasm by an Na-Ca exchange in the cell membrane which has a coupling ratio close to 3 Na+ for each Ca2+. To explain the full effects of changes in [Na]o and [Ca]o upon relaxation with the same Na-Ca exchange stoicheiometry it is necessary to assume that these changes in the bathing fluid affect [Na]i and that relaxation is dependent upon a single unbinding step, involving Ca2+ and the regulatory proteins. PMID- 4034922 TI - Secretion of parotid acinar granules in rats during reflex stimulation after chronic sympathectomy. AB - After chronic post-ganglionic sympathectomy the ultrastructure of 'resting' parotid acinar cells in rats remains relatively normal, despite the loss of nerve impulses normally causing secretion of acinar granules from this gland. The question whether eating hard chow still induces some acinar degranulation weeks after superior cervical ganglionectomy, has now been tested. It was found that scattered pockets of parotid acinar degranulation did occur. Some of these changes after unilateral denervation may have been attributable to intact sympathetic nerves arising from the contralateral superior cervical ganglion (Alm, Asking, Emmelin & Gjorstrup, 1984), but this cannot explain similar changes that occurred in glands after bilateral ganglionectomy. The possibility that some degranulation may be induced by circulating catecholamines was tested, 9-16 weeks after unilateral sympathectomy, by placing animals in the cold (0-4 degrees C) for 2 h before removal of tissues. Animals not given food during that time showed no evidence of parotid acinar degranulation, but those given hard chow showed extensive acinar degranulation in both parotid glands. On the sympathectomized side the degranulation was, however, less uniform and more patchy than on the side with an intact innervation. These findings agree with he belief that circulating catecholamines can, at times, induce degranulation of parotid acinar cells made supersensitive by chronic sympathetic denervation but, for it to occur, the cells must also be receiving parasympathetic stimulation at the same time. This interaction probably permits a sufficient turnover of granules to maintain a relative homoeostasis of the parotid acinar cells in rats. PMID- 4034923 TI - Fixation of radiation-induced potentially lethal damage by anisotonic treatment and its modification by DMSO or BrdUrd in V79 cells. AB - The effects of radiosensitization by bromodeoxyuridine (BrdUrd) substitution and radioprotection by dimethyl sulfoxide (DMSO) have been examined in relation to fixation and repair of radiation damage by anisotonic treatment. The fixation of radiation damage in cells exposed to 0.05 M or 1.5 M NaCl after irradiation was the same at equal survival levels irrespective of (BrdUrd) incorporation into the DNA. Also, during incubation between irradiation and a subsequent anisotonic treatment, cells containing BrdUrd repaired radiation damage to the same extents as cells without BrdUrd. DMSO treatment resulted in radioprotection. Fixation, by anisotonic salt treatment, of damage resulting from irradiation in the presence of DMSO was less extensive than from irradiation in the absence of DMSO, even though X-ray doses were adjusted to give equal survival levels. Recovery during incubation at 37 degrees C between irradiation and a subsequent salt treatment occurred for irradiation in the presence and absence of DMSO. These data show that the alteration of DNA radiosensitivity by BrdUrd had no effect on fixation or repair of radiation damage as assessed by salt treatment, while DMSO which is an OH scavenger caused the damage to be less susceptible to fixation and this damage was repaired during incubation at 37 degrees C. PMID- 4034924 TI - Evidence for the induction of two types of potentially lethal damage after exposure of plateau phase Chinese hamster V79 cells to gamma-rays. AB - The fixation of gamma-rays induced potentially damage (PLD) caused after treatment either with beta-araA or in medium made hypertonic by the addition of sodium chloride was studied in plateau phase Chinese hamster V79 cells. Treatment with beta-araA was found to affect a sector of PLD, the fixation of which specifically reduced the shoulder width of the survival curve. The effect was maximized when cell survival reached levels corresponding to an exponential line, with a slope similar to the final slope of the survival curve of untreated cells. This effect was achieved by a four hour treatment with beta-araA at concentrations above 150 microM. Longer treatment times or incubation at higher beta-araA concentrations did not significantly enhance the effect. Treatment in hypertonic medium, on the other hand, enhanced cell killing in a concentration dependent (NaCl-concentration) way and the survival reached values much lower than those corresponding to an exponential line. No indication for a plateau in the effect, indicating complete fixation of the sector of PLD that reacts sensitively to this treatment, was obtained. Both the slope and the shoulder width of the survival curve were affected, the slope first being increased after short treatment times (up to 10 min), followed by a decrease in the shoulder width after longer treatment times (longer than 10 min). Lesions fixed after treatment with beta-araA were repaired within four hours, whereas the repair of lesions fixed after treatment in hypertonic medium (460 mM NaCl, 30 min) appeared to be biphasic, with a fast component (completed in about one hour) correlated with a decrease in the slope and a slow component (completed in four hours) correlated with restoration of the shoulder width. Based on these results, we suggest that two types of PLD may be induced in plateau phase V79 cells after exposure to gamma-rays. One, the repair of which is completed within about one hour and which affects the slope of the survival curve, and a second, the repair of which takes place in a few hours and which specifically affects the survival curve shoulder width. The terms beta-PLD and alpha-PLD are suggested for the first and second component, respectively. Comparison of the repair rates of alpha PLD as measured with the help of beta-araA and of sublethal damage as measured in split-dose experiments indicated that these two cellular repair processes have very similar kinetics when measured under the same experimental conditions.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 4034925 TI - Self-renewal capacity of murine hemopoietic stem cells under internal contamination with 239Pu and 241Am. AB - The self-renewal capacity of murine pluripotent hemopoietic stem cells (CFU-S) of vertebral bone marrow was studied under conditions of short-term and long-term internal contamination with 239Pu or 241Am in female mice. Measurement of the CFU S self-renewal capacity was carried out using double transplantation assay. To evaluate the production of differentiated progeny of stem cells average erythroblast numbers/visible spleen colony and 59Fe-uptake/colony were computed. The marrow cellularity/vertebra and the number of CFU-S/vertebra were decreased and affected more by 239Pu than by 241Am. The production of erythroblasts per a single CFU-S and the 59Fe-uptake/colony were reduced, similarly the numbers of secondary spleen colonies and of secondary CFU-S in primary colonies. The above changes resulting from impaired functions of surviving CFU-S were more serious with 241Am than with 239Pu. The biological effects of plutonium and americium appeared independent of the phase of contamination. PMID- 4034926 TI - Lack of correlation between differentiation status and response to radiation of three murine squamous cell carcinomas. AB - The gross growth rate, histology, cellular kinetics, and in situ radiobiological response have been measured for three murine, keratinising squamous cell carcinomas that differed in their degree of differentiation. Growth rate was fastest in the least-differentiated tumour, slowest in the best-differentiated. However, the kinetics of the compartment of undifferentiated cells that are likely to be radiotherapeutically important, were the same for the three lines. There was no correlation between degree of differentiation and intrinsic or apparent radiosensitivity as measured by the growth delay assay. The radiobiologically best-oxygenated tumour was that which has the largest stromal component and this was not the best-differentiated tumour. PMID- 4034927 TI - Evaluation of radio- and chemotoxic effects of 125I-UdR on tumour growth and host survival. AB - The toxicity of 5-iodo-2'-deoxyuridine (I-UdR) was assayed in male C57 BL/6J mice bearing the syngeneic mammary adenocarcinoma EO 771 by injecting different doses of 'cold' I-UdR or 125-iodine labelled I-UdR. Host survival, tumour growth, DNA precursor incorporation, whole-body retention and tumour activity loss rates were chosen as biological end points. There was no measurable effect on host survival up to doses of 5 micrograms I-UdR or 50 microCi 125I-UdR per mouse during a mean life-span of 25 days. Adjusted to a constant amount of 0.55 micrograms I UdR/mouse, radiotoxicity of 125I-UdR on tumour growth (up to 17 days after implantation), tracer incorporation, whole-body and tumour retention (up to 12 days after 125I-UdR injection) could be excluded up to a dosage of 50 microCi 125I-UdR/mouse. It is concluded that in situ evaluation of tumour activity loss rates in carcinoma EO 771 is not disturbed by toxic effects of I-UdR or 125I-UdR within the dose limits mentioned. PMID- 4034928 TI - Clinical data for radiation embryology. Investigation programme 1967, report 1984. AB - In 1967 a prospective clinical study was started with the aim of providing optimum counselling for married couples who desire continuation of a pregnancy despite radiation exposure at an early stage as a result of X-ray diagnostics. Recommendations were devised as to whether an interruption of pregnancy should be applied for or not. These results were discussed repeatedly. Within the framework of the prospective study, embryological examinations were made in cases of interruption of pregnancy, and clinical and genetic examinations in cases of children who had been subject to radiation stress in utero. Up to July 1st 1984 nearly 200 cases of consultations have been or are being surveyed. The children were subjected to selected longterm examinations of up to 13 years. The results of cytogenetic, biochemical-genetic, clinical, and other examinations are considered and special characteristics of interesting cases are discussed. The conclusion was drawn that the recommendation to our patients to continue pregnancy in cases of exposure to radiation in utero below 0.1 Sv, was right. Furthermore the question arose of whether this dose limit could be increased. The study will be continued. PMID- 4034929 TI - On the microdosimetric definition of quality factors. AB - A formulation of the concept of quality factor based on the microdosimetric quantity lineal energy, y, is described. Toward this end, functions--denoted Specific Quality Functions (SQF)--are defined such that (a) they can be determined directly from observation and (b) a number of them can be used toward setting, by consensus, the values of a microdosimetrically-based quality factor. The determination of SQFs is exemplified by correlating data on the yields of dicentric aberrations in human lymphocytes with measured and calculated microdosimetric distributions. The implications of this approach to problems of radiation protection are discussed. PMID- 4034930 TI - Primary and secondary radiation doses from neon beam fragments. AB - The neon beam at 250 MeV/nucleon from the Bevalac at the Lawrence Berkeley Laboratory is bombarded in nuclear emulsion. The experimental interaction cross section of the neon beam in emulsion is 1078 +/- 35 mb, in agreement with the calculations from the modified Bradt and Peters formula. The secondary fragments were identified and their partial production cross sections were calculated. From the fluences of the primary and secondary fragments, we determine their radiation doses which are presented as a function of depth in the absorber. PMID- 4034931 TI - Effects of proliferation on the decay of thermotolerance in Chinese hamster cells. AB - Development and decay of thermotolerance were observed in Chinese hamster HA-1 cells. The thermotolerance kinetics of exponentially growing and fed plateau phase cells were compared. Following a 10-min heat exposure at 45 degrees C, cells in both growth states had similar rates of development of tolerance to a subsequent 45-min exposure at 45 degrees C. This thermotolerant state started to decay between 12 and 24 hr after the initial heat exposure. The decay appeared to initiate slightly sooner in the exponentially growing cells when compared to the fed plateau-phase cells. During the decay phase, the rate of thermotolerance decay was similar in the two growth conditions. In other experiments, cells were induced to divide at a slower rate by chronic growth (3 months) in a low concentration of fetal calf serum. Under these low serum conditions cells became more sensitive to heat and the rate of decay of thermotolerance remained the same for exponentially growing cells. Plateau-phase cells were also more sensitive, but thermotolerance decayed more rapidly in these cells. Although dramatic cell cycle perturbations were seen in the exponentially growing cells, these changes appeared not to be related to thermotolerance kinetics. PMID- 4034932 TI - Comparative study of the effects of hyperthermia and BCNU on BCNU-sensitive and BCNU-resistant 9L rat brain tumor cells. AB - 1,3-Bis(2-chloroethyl)-1-nitrosourea (BCNU)-sensitive and BCNU-resistant 9L rat brain tumor cells were treated with BCNU at graded temperatures between 37 and 44 degrees C. The cytotoxic effects of hyperthermia alone on both cell lines were the same. Treating both cell lines with BCNU at temperatures above 37 degrees C caused a progressive increase in cell kill. All survival curves for drug sensitive cells had shoulders followed by a region of exponential cell kill; dose enhancement ratios calculated at the 10% survival level ranged from 1.7 to 3.0. Survival curves for drug-resistant cells were exponential without a shoulder; dose enhancement ratios ranged from 3.3 to 8.4. For each cell line, a similar amount of the increased cell kill could be explained on the basis of the increases concentration of reactive species produced by hydrolysis of BCNU at elevated temperatures. The amount of cell kill that cannot be explained on this basis, however, suggests that factors other than an increase in the concentration of reactive species at higher temperatures are involved in the enhanced cell killing. Possible mechanisms include a heat-induced change in the structure of DNA chromatin and the effect of isocyanate deactivation of repair enzymes, both of which could lead to an increase in the number of crosslinks formed and therefore to an increase in cytotoxicity. PMID- 4034934 TI - Factors affecting the photokilling of cultured Chinese hamster cells by phthalocyanines. AB - Chloroaluminum phthalocyanine (CAPC) was recently shown to sensitize the inactivation of cultured Chinese hamster cells by visible light. Several factors affecting the photodynamic action of CAPC have been defined in the present study. Thus the photosensitized inactivation of Chinese hamster cells is not affected by superoxide dismutase, suggesting that O-2 radicals are not involved in the process. Postillumination treatments with D2O or heat (42 degrees C, 90 min) enhanced CAPC-induced photosensitivity, indicating the existence of a repair mechanism for photodamage. Preillumination treatments with sodium salicylate and 5-bromodeoxyuridine also enhanced photosensitivity. The later observation suggests that CAPC-induced DNA damage is potentially lethal. However, 3 aminobenzamide, a potent inhibitor of poly(ADP-ribose) synthesis which is involved in repair of DNA strand breakage, had no effect on the photosensitivity. Photosensitized inactivation by CAPC is dependent on the pH value of the medium during irradiation. Thus, in the range of pH values 6-8, the sensitivity was increased at the lower values. PMID- 4034933 TI - Effects of hyperthermia on DNA interstrand crosslinking after treatment with BCNU in 9L rat brain tumor cells. AB - The effects of hyperthermia (42 degrees C) on 1,3-bis(2-chloroethyl)-1 nitrosourea (BCNU)-mediated DNA interstrand crosslink formation were investigated in 9L rat brain tumor cells using the technique of alkaline elution. When cells were treated with 60 microM BCNU for 1 hr at 37 degrees C and incubated for 6 hr in drug-free medium at 42 degrees C, there was a 50% increase in crosslinking; and when cells were treated at 42 degrees C and incubated at 37 degrees C, there was a 45% increase in crosslinking compared with the results for cells treated and incubated at 37 degrees C. When cells were treated and incubated at 42 degrees C, there was a 129% increase in DNA crosslinking. The same relative order of results was found for cell survival. These results suggest that hyperthermia can increase DNA interstrand crosslink formation and the consequent cell death through two independent mechanisms: an increase in the amount of initial alkylation because of the increased rate of hydrolysis of BCNU at higher temperatures, and the effect of heat on DNA structure that leads to an increase in the number of crosslinks formed. PMID- 4034935 TI - Mortality of registered A-bomb survivors in Nagasaki, Japan, 1970-1984. AB - A follow-up study of A-bomb survivors registered in Nagasaki was conducted from 1970 to 1984 by the Scientific Data Center of A-Bomb Disaster at Nagasaki University, which has collected medical and administrative data on A-bomb survivors with the help of Nagasaki City Hall and other organizations. The purpose of this study was to investigate the following two points. (1) Has the health screening program for A-bomb survivors reduced the mortality rate? (2) If so, how much has it reduced it, and what would the life-shortening effect of radiation be without the health screening program? The results revealed that the effect of radiation on mortality would be underestimated if the health screening factor were ignored. The estimated effect of radiation dose was compared with that estimated by the Radiation Effects Research Foundation (RERF). PMID- 4034936 TI - X-ray and UV-radiation sensitivity of circulating lymphocytes in multiple epidermal cancer in relation to previous radiation exposure. AB - The cellular sensitivity to X rays (200 kV, 16 mA) and UV radiation (254 nm) was examined in lymphocytes from three groups of patients with multiple epidermal malignant tumors, selected by their clinical history of carcinogenesis. Eight patients previously exposed to low energy ionizing radiation (less than or equal to 12 kV) had an increased cellular sensitivity to UV radiation as well as X rays compared with 24 age and sex matched controls. This indicates the existence of a cellular cross-sensitivity to UV radiation and ionizing radiation not previously established for human cells. In contrast six patients previously exposed to high energy ionizing radiation (between 25 and 170 kV) had normal cellular response to both UV radiation and X rays, indicating a different biologic effect of low and high energy ionizing radiation. In the third group of patients, previously exposed to therapeutic UV radiation/excess sunlight, the lymphocytes had a normal response to X rays, but an increased sensitivity to UV radiation. The possibility of evaluating the individual risk at radiation exposure is suggested. PMID- 4034937 TI - Correlation of colony forming ability of mammalian cells with potassium content after hyperthermia under different experimental conditions. AB - When the potassium content of LM mouse fibroblasts was determined 16 hr after a heat treatment, a correlation was found between the concentration of potassium in the cell population and the level of cellular survival. When the cells were made thermotolerant, the degree of acquired heat resistance corresponded to a higher level of residual potassium. Also the degree of heat protection by erythritol corresponded to a higher level of residual potassium in the cells, while heat sensitization by procaine resulted in a lower level of potassium. It is concluded that the amount of residual potassium in these cells measured 16 hr after heat treatment may be considered as a suitable index for cell survival after hyperthermia treatment under different conditions. PMID- 4034938 TI - Ataxia telangiectasia cells exhibit the same radiosensitization response by incorporation of BrdUrd or IdUrd as do normal human cells. AB - Normal and ataxia telangiectasia (AT) human cells were exposed to 10(-5) mole/liter bromodeoxyuridine (BrdUrd) or iododeoxyuridine (IdUrd). High-pressure liquid chromatography (HPLC) measurements showed that up to 26 and 23% of the thymidine in DNA was substituted by BrdUrd in normal and AT cells, respectively. The incorporation of BrdUrd or IdUrd into DNA resulted in radiosensitization in normal and AT cells. When exposed to equal concentrations of BrdUrd and IdUrd, the BrdUrd caused greater radiosensitization than IdUrd in both normal and AT cells. PMID- 4034939 TI - [Long-term DNA damage and mammalian cell survival]. AB - On the basis of our own data and those reported in the literature we have made an attempt to follow the fate of the DNA lesions which remain unrepaired during a long period of time, and their possible role in the fate of irradiated cells. The presence of long-lived ("residual") damages is determined by the changes in survival of exposed cells treated, at different times after irradiation, with a mixture of arabinoside cytosine and hydroxyurea. It is shown that "residual" damages can probably exist in the exposed generation and be retained in that following the irradiated one, i.e. after the first mitosis. The nearest descendants of exposed cells (the 3d-5th generations) exhibit a 50% decrease in the rate of DNA synthesis and fall of their proliferative activity, as well as a decrease in the rate of reproduction of their remote descendants. The comparison of the results obtained with those reported by other authors enable us to assume that "residual" DNA lesions play an important role in the fate of exposed cells, that is, in reproductive death, radiation mutagenesis, and malignant transformations. PMID- 4034940 TI - [Mechanisms of radiation impairment of DNA biosynthesis. Separation, partial purification, characteristics of and changes in DNA polymerase alpha and beta activities of rat bone marrow at early stages after gamma irradiation and comparison with the status of repair and replication biosynthesis of DNA]. AB - Activity of alpha and beta DNA-polymerases in nuclei and cytosol and also replicative and repair biosynthesis of DNA in the bone marrow were determined during the first hours following whole-body gamma-irradiation of rats with a dose of 6 Gy. There was a pronounced and reliable correlation between postirradiation changes in activities of both DNA-polymerases in nuclei and also semiconservative and repair biosynthesis of DNA in bone marrow cells. The results were obtained by the method of separation and partial purification of alpha and beta polymerase the most important characteristics of which are presented. PMID- 4034941 TI - [Formal kinetic treatment of the possible role of proteins in DNA radiation tolerance, protection and sensitization]. AB - The formal-kinetic calculations have been made of the postirradiation behaviour of a "protein-DNA" water system with marked variations in protein and DNA concentrations. Protein is a strong competitive acceptor of active products of radiolysis of water and free radicals of DNA. The radioresistance of DNA in such a system and the influence of mercaptoethylamine, sensitizers and oxygen on DNA injury are discussed. The results of the calculations are compared with the data on the composition of cell nuclei and the data on the comparative radioresistance of cells, cell cycle, protective effects, and sensitization. In most cases, the results of the calculations do not contradict the experimental data. It is assumed that the protein protection may be the major factor in considering the endogenous radioresistance. PMID- 4034942 TI - [Formation of chromosome aberrations at different stages of the mitotic cycle in a culture of human lymphocytes irradiated with neutrons of average energy 0.35 and 0.85 MeV]. AB - Incidence of chromosome aberrations at different mitotic cycle stages of a human lymphocyte culture has been studied after exposure to 60Co-gamma-quanta (2 Gy) and neutrons of 0.85 Mev (1 Gy) and 0.35 MeV (0.5 Gy). The yield of chromosome aberrations with both gamma- and neutron-radiation depends on a stage of the mitotic cycle. The S stage is the most radioresistant one with both types of ionizing radiation. PMID- 4034943 TI - [Dynamics of changes in histomorphometric indices of skin following local irradiation]. AB - Recovery of the histomorphometric indices of rat skin at the period from 38 to 150 days following local X-irradiation with doses of 2.5-20 Gy has been studied. It is shown that the rate of restitution of the epidermis and dermis thickness is 0.0021 and 0.0037 days-1, respectively. However, the dermis thickness is less than in the control. The hair follicle density not only fails to restore after irradiation with a dose of above 10 Gy but continues decreasing in time. PMID- 4034944 TI - [Change in survival of cells in the first 2 generations after irradiation and exposure to inhibitors of repair synthesis]. AB - In experiments on asynchronous population of HeLa S3 cells a study was made of the possibility of assessing DNA lesions which remained unrepaired for a long period of time following gamma-irradiation: in generation "O" directly affected by radiation and in generation "I" following the irradiated one. The presence of DNA damages was estimated by the reduction in survival of exposed cells incubated with inhibitors of repair and replicative syntheses of DNA, namely, with arabinoside cytosine and hydroxyurea. A considerable enhancement of the radiation effect was noted with the inhibitors added 0-6 h after irradiation (generation "O"), and a marked increase in the cell death was registered with the preparations injected 24-30 h after exposure (generation "I"). It is assumed that minor residual lesions persist in the generation of cells, following the one directly affected by gamma-radiation, which have completed the first postirradiation mitosis. PMID- 4034945 TI - [Sensitivity of DNA synthesis to gamma-irradiation in Ehrlich ascites carcinoma cells in stationary and logarithmic growth phases]. AB - A study was made of the influence of gamma-radiation on DNA synthesis in cells of 3-day and 7-day Ehrlich ascites tumor cultures. DNA synthesis in cells of the 3 day culture was more sensitive to moderate radiation doses than those of the 7 day culture as was observed during the first 30 min after irradiation. After 3 hour postirradiation incubation, no appreciable difference was noted in radiosensitivity of DNA synthesis in the cells of the 3-day and 7-day cultures. PMID- 4034946 TI - [Radiosensitivity and postirradiation dynamics of granulocyte-macrophage precursors (CFU-DC) in the bone marrow of 2 lines of mice--CBA and BALB/c]. AB - CFU-DC in the bone marrow of CBA and BALB/c mice, which are contrast in total radiosensitivity, have close characteristics: D0 is 1.35 and 1.32 Gy, respectively. The proliferation rate of CFU-DC after single exposure to a non lethal dose of 4 Gy is higher in CBA than in BALB/c mice. The time of doubling the CFU-DC population during the period of exponential growth after irradiation is 40 and 72 h for CBA and BALB/c mice, respectively. PMID- 4034948 TI - [Morphofunctional state of vascular wall components in the rat brain following gamma-irradiation of the head]. AB - The histochemical methods were used to study alkaline phosphomonoesterase of capillaries, glycosaminoglycanes of vascular walls, and tissular basophils of rat brain after local gamma-irradiation of the head with doses of 51.6-645 mC/kg. During the first minutes and hours after irradiation, the actively functioning capillary network lengthened and secretion of indolylamines by tissular basophils increased. It is assumed that the changes observed are compensatory. PMID- 4034947 TI - [DNA content of rat organs damaged by strontium-90 during the development of delayed effects]. AB - In this report the results are submitted concerning the frequency of disorders in the nucleic acid metabolism in the bone marrow, peripheral blood, thymus and spleen of rats during a year after single injection of 90Sr. Irrespective of the time lapsed after the injection of the radionuclide 10-30% of animals did not exhibit any substantial changes in the nucleic acid metabolism in all the organs under study except the thymus. PMID- 4034949 TI - [Comparative assessment of the danger of inhaling 239Pu and 241Am based on the degree of leukopenia in dogs]. AB - From the analysis of the results of examination of 96 dogs it is concluded that the estimate of a relative danger of breathing transuranium radionuclides with different metabolism rates (polymeric 239Pu and monomeric 241Am), according to degree of leukopenia is more reliable when it is compared with a mean weighed dose per whole organism than the dose per individual "critical" organ. PMID- 4034950 TI - Generation of three dimensional images from CT scans: technological perspective. AB - Routine production of three dimensional (3-D) surface images from CT scans for clinical applications has been performed in 700 cases. These images have been found useful in craniofacial, orthopedic, and neurosurgical applications. Three dimensional images may be produced on the same CT scanner that collected the original slices. The emergence of 3-D imaging as a routine radiological procedure involves special technological requirements to avoid artifacts and to produce a useful result. Three dimensional surface reconstruction procedures are reviewed and examples of clinical application are presented. PMID- 4034951 TI - Magnetic resonance imaging: the basic physical and clinical concepts. Part I. AB - Noninvasive evaluation of the human body has become an essential tool in the diagnosis of disease processes. Recent developments in nuclear magnetic resonance imaging (MRI) have extended a powerful chemical analytic technique to the medical imaging field. This article presents the fundamental principles of MRI in terms of the concept of transmission and reception of energy. The physical principles of spin resonance are discussed in Part I. Spin relaxation and pulse sequences will be examined in Part II and III. A selected bibliography directs the reader to a more detailed discussion of the pertinent physics. PMID- 4034953 TI - The ECE trilogy. PMID- 4034954 TI - Brain tumors: detection and typing by use of CPMG sequences and in vivo T2 measurements. AB - A spin-echo sequence with 24 echoes (Carr-Purcell-Meiboom-Gill sequence) was evaluated to determine the usefulness of magnetic resonance (MR) in detecting and typing brain tumors. The TEs in these examinations were between 28 and 346 msec, and the TR was 860, 1260, or 1660 msec. The results of the MR examination of 32 histopathologically proved tumors are presented. All but one tumor could be detected by MR. Tumors generally were obvious on MR due to the higher contrast enhancement of these lesions, especially with a TE longer than 100 msec. T2 values calculated from an eight-point fit, however, did not allow discrimination of different tumors, nor did they allow differentiation between tumor, inflammatory tissue, and demyelination. PMID- 4034952 TI - Intraoperative radiotherapy: an overview. AB - At our institution, we plan to carry out intraoperative radiation therapy in a carefully selected group of patients with localized but unresectable cancers or resected cancers with a high probability of local recurrence. We believe that this innovative procedure will improve survival and quality of life in certain cancer patients. PMID- 4034955 TI - Cervical spinal fractures: CT detection. AB - Although computed tomography (CT) is commonly used in addition to plain radiographs to evaluate cervical spinal fractures, it may fail to detect some clinically significant fractures. Cervical spinal fractures were produced in cadavers, studied with CT, and documented by cryomicrotomy. The CT scans were interpreted independent of the anatomic sections. Pedicle and lateral mass fractures were regularly unrecognized on CT scans. In these cases, widening and hemarthrosis of the adjacent facet joints were evident. A widened facet joint is an indirect sign of an occult cervical spinal fracture. PMID- 4034956 TI - CT of thyroglossal duct cysts. AB - A retrospective analysis of surgically proved cases of thyroglossal duct cysts was performed in an attempt to determine the characteristics of these lesions using computed tomography (CT). We evaluated 12 preoperative cases and two cases with postoperative complications. Ten patients with lesions that could be confused either clinically or radiographically with these cysts were also evaluated to develop a systemized radiologic differential diagnostic approach for the evaluation of anterior triangle neck lesions. CT enables the differentiation of thyroglossal duct cysts from other anterior triangle lesions based on location, CT values, and alterations in the adjacent soft tissues. PMID- 4034957 TI - Esophageal speech: double-contrast evaluation of the pharyngo-esophageal segment. AB - Alaryngeal voice is usually accompanied by esophageal speech; however, about 40% of laryngectomy patients are unable to achieve adequate esophageal speech and must rely on mechanical devices for communication. A technique was developed for performing double-contrast studies of the hypopharynx, cervical esophagus, and pharyngo-esophageal segment using thick barium and the air normally injected for speech. Simultaneous audio and video recordings obtained during esophageal speech allowed correlation of the quality of speech with the motion of the pharyngo esophageal segment. In 35 patients with various degrees of fluency in esophageal speech, normal and abnormal function of the pharyngo-esophageal segment was documented. Inadequate esophageal speech can be related to abnormal motion of the pharyngo-esophageal segment. PMID- 4034958 TI - The temporomandibular joint: magnetic resonance imaging using surface coils. AB - A total of 115 temporomandibular joints (TMJ) in 67 patients were examined by high resolution magnetic resonance (MR) using a surface coil. Five millimeter sections were imaged using a two-dimensional multisection acquisition. Findings of MR examinations were correlated with findings of conventional radiographic and clinical examinations. Surgical confirmation was available in 15 patients. MR definition of soft-tissue structures including the meniscus is superior to that of conventional imaging methods. Bony detail is comparable. MR is an excellent method for the primary diagnostic evaluation of TMJ abnormalities. PMID- 4034959 TI - Wilson disease of the brain: MR imaging. AB - Twenty-three patients with biochemically proved Wilson disease underwent magnetic resonance (MR) imaging of the brain. Positive findings, believed secondary to this condition, were found in 15 subjects. Findings varied among patients, but there were striking similarities between certain groups of patients. Areas of abnormal signal were seen in the lenticular, thalamic, caudate, and dentate nuclei, as well as in the brain stem; in these areas, the abnormalities were bilaterally symmetric. A smaller number of patients had asymmetric focal white matter lesions. Correlation of the MR findings with clinical symptoms was generally good. Repeat imaging was performed on five patients at intervals ranging from 4 to 8 months; none showed significant interval change. PMID- 4034960 TI - Sellar and juxtasellar lesion detection with MR. AB - We compared the effectiveness of magnetic resonance (MR) imaging and computed tomography (CT) in evaluating sellar and juxtasellar lesions. Fifty-five lesions were imaged with a Technicare 0.5-T superconducting MR imager and GE 9800 and 8800 CT scanners: 26 pituitary adenomas (including six microadenomas), six craniopharyngiomas, two empty sellae, five meningiomas, four optic chiasmal gliomas, five hypothalamic gliomas, two giant aneurysms, and one each of teratoma, gasserian ganglion neuroma, histiocytoma, cholesteatoma, and metastases. Although CT scans showed the abnormalities in most cases, MR was superior in delineating distortions of the optic chiasma and other suprasellar structures, and in demonstrating the status of the carotid arteries. MR can reveal fat, hematoma, and cyst and can be used to differentiate the pathologic features of many lesions. Microadenomas that do not enlarge the sella were not demonstrated with current MR techniques. PMID- 4034961 TI - Supraacetabular insufficiency fractures. AB - Insufficiency fractures in the supraacetabular region were identified in five women, aged 55-83 years. Factors contributing to the diminished resistance of their bones included postmenopausal osteoporosis, steroid therapy, radiation therapy, and rheumatoid arthritis. The supraacetabular fractures were seen on routine radiographs as hazy bands of sclerosis located immediately above and parallel to the acetabular roof. All five patients had additional fractures in the spine or pelvis. Supraacetabular insufficiency fractures may be an unsuspected cause of hip pain, especially in older women. PMID- 4034962 TI - The uterus: in vitro MR-anatomic correlation of normal and abnormal specimens. AB - Magnetic resonance (MR) images of 12 fresh uterine specimens obtained with a high resolution surface coil were correlated with findings on gross and microscopic pathologic examination. The uterine wall can be differentiated into three distinct zones: a central high-intensity zone, a junctional low-intensity band, and a peripheral medium-intensity area. Whereas the endometrium (basale and functionale) corresponded to the high-intensity zone, the myometrium correlated best with the combined width of the areas of low and medium signal intensity. The signal intensity of a leiomyoma varied, depending on its cellularity. Primary endometrial and cervical carcinomas were clearly shown on MR images, as were other abnormalities such as adenomyosis and Nabothian cysts. The potential usefulness of MR imaging in detecting and staging uterine neoplasms is discussed. PMID- 4034963 TI - Diffuse peripheral lung disease: evaluation by high-resolution computed tomography. AB - High-resolution computed tomography (HRCT) was performed on 15 patients who had diffuse peripheral lung disease, and the findings were compared with those of conventional chest radiography and histologic examination. Bullae, interstitial fibrosis with honeycombing, and small granulomas were more clearly and specifically demonstrated on HRCT scans than on conventional chest radiographs in all patients. Histologically proved mild alveolar wall thickening due to alveolitis in cases of sarcoidosis and systemic lupus erythematosus was not detected. HRCT is useful for performing detailed morphological analyses of abnormalities of the peripheral portions of the lung. PMID- 4034964 TI - T1N0M0 bronchogenic carcinoma: assessment by CT. AB - We reviewed medical records and conventional chest radiographs that showed a solitary T1N0M0 nodule in 23 patients who had non-oat-cell bronchogenic carcinoma. No patient had evidence of metastases, either on the chest radiograph or clinically. All patients underwent computed tomography (CT) examination of the thorax, including the adrenal glands. Only one patient (4%) had mediastinal lymph nodes greater than 1 cm in diameter accessible to mediastinotomy; anterior mediastinotomy confirmed metastatic spread in this patient, which precluded curative resection. Three patients each had a mildly enlarged (2 cm or less) adrenal gland; however, follow-up study suggested that metastasis was not the cause of adrenal enlargement in these patients. This study reinforces concern over whether CT is warranted in the preoperative assessment of T1N0M0 bronchogenic carcinoma. PMID- 4034965 TI - Pleural and chest wall invasion in bronchogenic carcinoma: CT evaluation. AB - CT scans of 47 patients who had peripheral bronchogenic carcinoma contiguous to the pleural surface and who had undergone thoracotomy were retrospectively reviewed. The CT features of the primary neoplasm that were analyzed included the angle and amount of contact with the adjacent pleural surface, associated pleural thickening, fat plane between the tumor and chest wall, rib destruction, and chest wall mass. CT was of limited predictive value in separating those patients who had parietal pleural/chest wall involvement from those who did not. The combination of two or three CT findings (obtuse angle, greater than 3 cm contact with pleural surface, associated pleural thickening) resulted in a sensitivity of 87% and a specificity of 59%. The clinical symptom of focal chest pain, while not as sensitive (67%) as CT, was much more specific (94%) for parietal pleura/chest wall invasion. PMID- 4034966 TI - Thoracic wall involvement by Hodgkin disease and non-Hodgkin lymphoma: CT evaluation. AB - Thoracic computed tomographic (CT) scans of 250 patients with newly diagnosed or recurrent lymphoma revealed thoracic wall involvement in 24 patients (11 with Hodgkin disease, 13 with non-Hodgkin lymphoma). Thoracic wall involvement occurred without contiguous mediastinal or parenchymal involvement in 17 patients. Of these, 13 patients had masses beneath the pectoralis muscles or within the breast, and four had masses arising from the ribs. Five additional patients had mediastinal masses with thymic involvement and parasternal extension through the thoracic wall. Pulmonary parenchymal lymphoma with thoracic wall invasion was noted in the remaining two patients. In five of nine patients receiving radiation therapy, treatment plans were modified by CT demonstration of thoracic wall lymphoma. PMID- 4034968 TI - CT measurement of the diameter of spinal and other bony canals: effects of section angle and thickness. AB - The effects of section angle and thickness on the measurement of spinal canal diameter by computed tomography (CT) were tested. A phantom of three spinal canals was constructed of three Lucite rods of different diameters, each covered with 1.8-mm-thick Teflon. A second phantom was constructed of two Lucite rods of the same diameter covered with 1.8- and 8.8-mm-thick Teflon, respectively. CT sections 10, 5, and 1.5 mm thick were obtained at various angles relative to the transverse plane of each canal. Anteroposterior diameters were measured at bone window settings using a standard software package and a method that uses a CT number profile. Results show that sections obtained at an angle to the transverse plane of the canal do not always overestimate its diameter, as previously suggested, but can make it appear artifactually stenotic. The effect is from volume averaging and is most marked when thick, severely angled sections are used. PMID- 4034967 TI - Abdominal tuberculosis: CT evaluation. AB - The computed tomography (CT) scans of 27 patients with abdominal tuberculosis were reviewed retrospectively to determine the range of abdominal involvement. Most patients had been at increased risk because of intravenous drug abuse, alcoholism, acquired immunodeficiency syndrome (AIDS), cirrhosis, or steroid therapy. The etiologic agent was Mycobacterium tuberculosis in 23 patients and M. avium-intracellulare in four patients with AIDS. In five patients, tuberculosis was limited to the abdomen. CT findings included adenopathy, splenomegaly, hepatomegaly, ascites, bowel involvement, pleural effusion, intrasplenic masses, and intrahepatic masses. Characteristic features were a tendency for adenopathy to prominently involve peripancreatic and mesenteric compartments, low-density centers within enlarged nodes, complex nature of the ascites, and adenopathy adjacent to sites of gastrointestinal tract involvement. Recognition of these manifestations and maintenance of an index of suspicion, especially in patients at risk, should help optimize the correct diagnosis and management of intraabdominal tuberculosis. PMID- 4034969 TI - Nonpalpable breast lesion localization using a curved-end retractable wire. AB - A new needle-wire system has been developed for localization of nonpalpable breast lesions. The curved-end wire, which is made of a tough pseudoelastic alloy, eliminates many of the pitfalls of this procedure for both the radiologist and the surgeon. Advantages of this new system include the ability to anchor the needle during filming, the ability to easily reposition the needle if necessary, the option of injecting dye, the inability to transect the wire during surgery, and the option of leaving both the needle and wire in place in the subject to allow easier dissection during biopsy. PMID- 4034970 TI - Pulse selection chart for brain MR imaging sequences. AB - A chart for organizing, teaching, and recording the magnetic resonance (MR) pulse sequences used for brain and cervical spine imaging is described. The chart helps document workable sequences and facilitates comparisons between different sequences. It has also been helpful in instructing residents and fellows how to approach an MR examination logically. PMID- 4034971 TI - A doubly curved guide wire for use in the subclavian/vertebral artery system. PMID- 4034972 TI - Guide wire extension. AB - Any specialized guide wire can be converted to an exchange guide wire by the addition of an eyelet on its stiff end to which an extension guide wire may be hooked. PMID- 4034973 TI - Re: The quick aortic turn. PMID- 4034974 TI - Breast cancer: postoperative radiation therapy. AB - Postoperative radiation therapy reduces the proportion of regional recurrences following radical mastectomy for cancer of the breast. Only a small number of patients with tumor beyond surgical effectiveness and without distant metastases stand to benefit. Improvement of final results due to postoperative radiation therapy can only be shown in large series of cases. PMID- 4034975 TI - Diaphanography in the diagnosis of breast cancer. AB - In diaphanography, a light source is applied to the breast to visualize lesions through a television camera sensitive to infrared light. Diaphanography and mammography were performed on 1,476 patients in a screening population. Twenty six cancers in 24 patients were confirmed by biopsy; detection rates were 96% for mammography, 58% for diaphanography, and 62% for physical examination. Mammography was significantly more sensitive than either diaphanography or physical examination (p less than 0.005). Mammography detected 10 cancers that were missed at physical examination, whereas diaphanography detected five such lesions. It is concluded that diaphanography does not satisfy the criteria of a screening procedure, but because the examination is completely innocuous, it may serve as an adjunct to physical examination. In addition, the authors developed a breast model for diaphanography that appears to correlate with the human breast and demonstrates some of the physics and limitations of diaphanography. PMID- 4034976 TI - Fibrinolysis in chronic arteriosclerotic occlusions: intrathrombotic injections of streptokinase. Work in progress. AB - Forty-seven patients with chronic arteriosclerotic occlusions of iliac and femoropopliteal arteries were treated by intrathrombotic fibrinolysis. The occlusions were 10-65 cm (mean, 22 cm) long and 6 weeks to 2 years (mean, 4.5 months) old. By means of consistent intrathrombotic injections of 2,500 units of streptokinase every 5 minutes, the thrombi were recanalized within 1-7 hours (mean, 2.5 hours). The primary recanalization rate was 75% (35/47), the patency rate after 2 weeks, 68%. In 29 patients (62%), a residual stenosis had to be dilated by balloon angioplasty. Because of the low total dose of streptokinase (mean, 70,000 units), the thrombin time was elevated up to twice the normal value in only one patient. Bleeding that required transfusions was observed in only two patients (4%). Advantages of intrathrombotic fibrinolysis include higher recanalization rate, lower total dose of streptokinase, fewer bleeding complications, and shorter therapy time than previously reported with other treatments. PMID- 4034977 TI - Complications of percutaneous nephrostolithotomy. AB - In 224 patients, renal stones were removed from the urinary tract using either direct extraction with a basket or forceps (59 patients), ultrasonic lithotripsy (164 patients), or infusion chemotherapy (one patient). Residual stone fragments were present more frequently in patients treated with ultrasonic lithotripsy (27%) than with direct extraction (5%). Other complications included hemorrhage (eight patients), catheter dislodgement (four patients), large amounts of urine extravasation (three patients), glycine ascites (three patients), infection (two patients), pneumothorax (one patient), and a prolonged ileus (one patient). More complications occurred among the first 50 patients than the last 50 patients, even though more difficult cases, including patients with staghorn calculi, were accepted during the latter period. Although a learning curve exists, complications can be minimized by attempting to treat more favorable cases during the initial experience. PMID- 4034978 TI - Esophageal rupture: complication of balloon dilatation. AB - Recent studies have emphasized the safety of fluoroscopically guided balloon dilatation for treatment of severe esophageal strictures. A case of esophageal rupture that followed dilatation of a distal esophageal stricture with a 20-mm balloon catheter is reported. PMID- 4034979 TI - Impassable urethral strictures: percutaneous transvesical catheterization and balloon dilatation. AB - Urethral strictures that are impassable in retrograde fashion present a special problem to the urologist because they cannot be managed by standard dilatation techniques or direct-vision internal urethrotomy. Open urethroplasty is usually required. We describe a technique to catheterize the urethra in an antegrade fashion and dilate the strictures. Our study involved six patients with impassable urethral strictures that were successfully traversed and dilated. Percutaneous transvesical antegrade catheterization and balloon dilatation are beneficial for patients with bladder outlet obstruction. PMID- 4034980 TI - Adult respiratory distress syndrome in children. AB - Clinical, radiological, and pathologic data for nine children with adult respiratory distress syndrome (ARDS) were reviewed. The children ranged in age from 7 months to 15 years (mean age, 7.4 yrs). Underlying diseases and precipitating events included sepsis, pneumonia, near drowning, aspiration pneumonia, central nervous system trauma, and malignancy. All patients had the rapid onset of diffuse bilateral lung opacification, required assisted ventilation for periods of 5-86 days (mean, 25.2 days), and received high levels of inspired oxygen for 2-41 days (mean, 12.7 days). Eight patients manifested air leak complications; these problems persisted until the patients died or were weaned from the respirator. Five of the nine patients died. Autopsy in three patients demonstrated alveolar duct fibrosis characteristic of the late proliferative phase of ARDS and consistent with oxygen toxicity. Two survivors demonstrated mild restrictive changes on follow-up pulmonary function tests and showed persistent linear densities on chest radiographs. PMID- 4034981 TI - Chest radiographic findings in neonates on extracorporeal membrane oxygenation. AB - Eight full-term neonates with pulmonary failure were managed with extracorporeal membrane oxygenation (ECMO). Chest radiographs obtained before and during ECMO support were reviewed. During periods of increased flow requirements, the chest radiographs were difficult to evaluate because of increasing pulmonary opacity. During periods of the infants' clinical improvement, their chest radiographs tended to improve as well. A direct cause-and-effect relationship between the pulmonary density and the ECMO flow requirements has not yet been established. The chest radiographs were reliable in confirming correct catheter positions. Routine daily examinations did not demonstrate unsuspected abnormality. Chest radiography during periods of clinical instability, however, added confirmatory evidence to some clinical diagnoses and assisted us in making the diagnosis of an unexpected pneumothorax. PMID- 4034982 TI - Lung abscesses in children: diagnostic and therapeutic needle aspiration. AB - Three children aged 17 months to 17 years developed right-sided peripheral lung abscesses. Clinical signs were fever and cough. Laboratory cultures were negative, and the patients did not respond to appropriate antibiotic coverage. Under fluoroscopic guidance, purulent material was removed from the abscesses by needle aspiration. The patients became afebrile within 24 hours; none suffered complications of bleeding or pneumothorax. Cultures of the aspirate were positive for microorganisms sensitive to the prescribed treatments. A simple aspiration technique is described and proposed as useful for selected patients when surgical drainage is recommended. There was no morbidity in our cases, and recovery from a typically prolonged course was shortened by the procedure. PMID- 4034983 TI - Intracranial hematomas: imaging by high-field MR. AB - Twenty intracranial hematomas between 1 day and over 1 year old were imaged using magnetic resonance at 1.5 T, with T1- and T2-weighted spin-echo pulse sequences. Characteristic intensity patterns were observed in the evolution of the hematomas, which could be staged as acute (less than 1 week old), subacute (greater than 1 week and less than 1 month old), or chronic (greater than 1 month old). Acute hematomas were characterized by central hypointensity on T2-weighted images (WIs). Subacute hematomas had peripheral hyperintensity on T1-WIs and then on T2-WIs. This hyperintensity proceeded to fill in the hematoma in the chronic stage. In subacute and chronic hematomas, there was hypointensity on T2-WIs in the immediately adjacent part of the brain. On T2-WIs of acute and subacute hematomas, the nearby white matter was characterized by hyperintensity, consistent with edema. A different mechanism is proposed for each of the three characteristic intensity patterns. Two of these mechanisms increase in proportion to the square of the magnetic field magnitude. PMID- 4034984 TI - MR technology: effect of even-echo rephasing on calculated T2 values and T2 images. AB - In multiple spin-echo image sequences of blood flow, the "even-echo" phenomenon produces an absolute increase in signal magnitude from first- to second-echo images of normal vessels harboring slow flow. Distinguishing this from the apparent relatively high signal intensity seen on second-echo images in pathologic foci of stationary tissue is important to the diagnostician. Selected case material containing two tissue types was reviewed retrospectively: tissues known to harbor slow flow, such as normal veins and venous sinuses and vascular malformations, and tissues that have long transverse (T2) relaxation times and appear as intense structures on second-echo images, such as neoplasms, infarcts, and regions of demyelination. Calculations of T2 parameters were made by computer for defined regions of interest. T2 images were also generated. Visual inspection of the acquired images did not reliably distinguish increased intensity due to even-echo rephasing from the relative changes between adjacent tissues seen on second-echo images. More definitive differentiation of the even-echo phenomenon was provided by calculated values of T2 and computer-synthesized T2 images representing acquired intensity data of two-echo sequences. The synthesized images were especially useful when stationary tissue with lengthened T2 values was adjacent to or in proximity to vessels or vascular lesions. A five spin-echo image sequence was valuable for separating slow flow from stationary tissue by a technique of synthesizing T2-difference images using three consecutive echoes. PMID- 4034985 TI - Neurochemical and cognitive aspects of depression. PMID- 4034986 TI - Effects of trichothecenes (T-2 toxin) on protein synthesis in vitro by brain polysomes and messenger RNA. AB - The effects of T-2 toxin on protein synthesis were tested in two reticulocyte lysate in vitro systems pretreated with micrococcal nuclease. One of the test systems contained purified globin mRNA and was initiation dependent. The other contained rat brain polysomes and incorporated amino acids by an elongation dependent process. T-2 toxin inhibited the translation of globin mRNA at all concentrations tested, from 10(-8) M to 10(-4) M. Rat brain polysomes were much less sensitive to T-2 toxin than globin mRNA. While high concentrations of the toxin (10(-4) M) led to partial inhibition of protein synthesis by polysomes, low concentrations (10(-8) M and 10(-6) M) stimulated protein synthesis. Comparison of the above results with those obtained by other workers suggest that the T-2 toxin may inhibit not only the initiation step of translation, but also elongation and termination, depending upon the concentration of the toxin and the nature of the translation system. A similar mechanism may operate for all the trichothecene toxins that exert their effect through binding to ribosomal peptidyl transferase. PMID- 4034987 TI - Endogenous breath acetaldehyde levels among alcoholic and non-alcoholic probands: effect of alcohol use and smoking. AB - The effects of possible confounding factors on endogenous breath acetaldehyde levels were examined in alcoholic and non-alcoholic subjects. Demographic characteristics, family history for alcoholism, smoking and drinking history, and breath acetaldehyde levels were assessed. Differences in endogenous breath acetaldehyde levels could not be attributed to age, sex, or having a family history positive for alcoholism. Individuals who smoke or abuse alcohol had higher endogenous breath acetaldehyde levels than persons who did not. PMID- 4034988 TI - Elevated endogenous breath acetaldehyde levels among abusers of alcohol and cigarettes. AB - Endogenous (fasting) breath acetaldehyde levels were assessed as a discriminator between alcoholic and non-alcoholic subjects. The influence of smoking as a potential confounding variable on breath acetaldehyde was determined. Individuals with a history of smoking and/or drinking had higher endogenous breath acetaldehyde levels as compared to controls. Mean acetaldehyde levels revealed an additive (noninteractive) pattern associated with combined abuse of these substances. The similarity in acetaldehyde levels between alcoholic non-smokers and non-alcoholic smokers limits the usefulness of endogenous breath acetaldehyde for the purpose of early diagnosis of alcoholism. Results support hypotheses that elevations in acetaldehyde could be a common factor in disease associated with alcohol and cigarette abuse. PMID- 4034989 TI - Positive interaction between leukotriene C4 and histamine and other mediators on vascular tissues. AB - The interaction of leukotriene C4 (LTC4) with the contractile activity of histamine (H), serotonin (5HT) and norepinephrine (NE) has been investigated in isolated vascular preparations. Threshold concentration of LTC4 (5 X 10(-9) M) significantly potentiated the vasoconstricting effect of these compounds on guinea-pig pulmonary artery (GPPA). This phenomenon was long-lasting for H since it was still present 40 min after LTC4 had been washed. FPL-55712 (10(-5) M) counteracted the increased H response on GPPA induced by LTC4. Potentiation of H activity due to LTC4 was also observed on guinea-pig thoracic aorta (GPTA) indicating that LTC4-induced hyperreactivity is not a phenomenon restricted to the pulmonary vascular bed. In the experiments carried out in presence of indomethacin (3 X 10(-6) M), LTC4 still potentiated H-induced vasoconstriction on GPPA, however the time course of the phenomenon was significantly shorter than that observed in absence of the cyclooxygenase inhibitor. The contractile activity of H and NE on guinea-pig portal vein (GPPV) was not potentiated by LTC4. These results demonstrate that LTC4 induces hyperreactivity of the arterial vascular tissue to vasoactive compounds and suggest that cysteinyl-leukotrienes may have pathological significance in the hemodynamic changes occurring during anaphylactic reactions. Preliminary experiments carried out on human intralobar pulmonary artery strongly support this hypothesis. PMID- 4034990 TI - Identification of the hatching factor of the barnacle Balanus balanoides as the novel eicosanoid 10,11,12-trihydroxy-5,8,14,17-eicosatetraenoic acid. AB - Barnacle egg hatching factor which is released into the mantle cavity where the egg masses are brooded and stimulates embryonic musculature resulting in hatching and liberation of the larvae into the sea has been isolated in a purified form from a common barnacle Balanus balanoides. Derivatised hatching factor has been analysed by GC-MS and identified as 10,11,12-trihydroxy-5,8,14,12 eicosatetraenoic acid, a novel eicosanoid probably formed from endogenous eicosapentaenoic acid (20:5w3). Hatching factor activity is the first specific physiological function to be established for this type of compound. PMID- 4034991 TI - Study of diet and drug interactions on prostanoid metabolism. AB - To study the extent to which combinations of different dietary lipids stimulate or inhibit prostanoid synthesis groups of 12 rats were fed diets containing 10% (w/w) of either safflower oil, hydrogenated coconut oil/safflower oil, cod liver oil/safflower oil or cod liver oil/linseed oil for a period of four weeks. All diets, with the exception of the safflower oil feed, contained similar levels of linoleic acid. Two further groups of rats placed on the cod liver oil diets were injected with indomethacin (4 mg/kg, i.p.) every three days to establish the completeness of dietary prostaglandin (PG) inhibition. In spite of a 20 fold difference in dietary linoleic acid content, the safflower oil group had similar PG generating capacities to the saturated fat control group, suggesting tight metabolic control of PGs and their precursors. Although there were prostanoid variations in tissue responses, both of the cod liver oil diets substantially reduced generation of aortic, whole blood and renal prostanoids, and decreased urinary PG excretion. The degree of inhibition of renal PGs was substantially greater in the cod liver oil/linseed oil group, with prostaglandin levels being 35% lower than those observed in the cod liver oil/safflower oil fed animals suggesting that linolenic acid and the marine oil fatty acids act synergistically to inhibit formation of 2-series prostaglandins. Concurrent administration of omega-3 fatty acids and indomethacin reduced PG levels further than those obtainable by diet alone, demonstrating that the diets did not result in maximal inhibition. Awareness of these various effects is important for both physiological or clinical studies in which dietary manipulations are used as a means of modifying prostanoid synthesis. PMID- 4034992 TI - Antigen-induced leukotriene release from rat lung in vitro. AB - Chopped lung from inbred hyperreactive rats was challenged with antigen following active or passive sensitization and supernatants were assayed for the presence of leukotrienes (LTs) by radioimmunoassay. Dose-related increases in the release of LTC4- and LTB4-immunoreactive material were obtained with significantly more material being released following passive sensitization. Chromatographic analysis indicated the presence of LTB4, LTC4 and LTE4. When LT release in inbred rats was compared to Sprague-Dawley or Fischer rats, the amounts released were as follows: Inbred greater than Sprague-Dawley greater than Fischer. It was concluded that the release of LTs in the three strains correlated with the degree of non specific bronchial hyperreactivity. PMID- 4034993 TI - Prostaglandin F and E levels in the conceptus, uterus and plasma during early pregnancy in the ewe. AB - Concentrations of prostaglandins E and F (PGE and PGF) were measured in the embryo or fetus, extra embryonic or fetal membranes (membranes), intercaruncular and caruncular endometrium and plasma collected from uterine and ovarian arterial and venous vessels from separate groups of ewes laparotomized at 5 day intervals from day 10 to day 55 of pregnancy. Our purpose was to investigate the role of prostaglandins E and F in the maternal recognition of pregnancy, implantation and early placental function. Our data suggest that the initial maintenance of the corpus luteum in the pregnant ewe does not involve a reduction in PGF production, compared to pregnant ewes; but a change in the pattern of PGF secretion. This is accompanied by an elevation in PGE production of similar magnitude to that observed in non pregnant ewes. The extra embryonic/fetal membranes appear to be the major source of elevated PGF levels in the maternal circulation prior to day 30 of pregnancy. Between days 35 and 55 of gestation the rising PGF levels in maternal serum probably come from the fetus. Over the same period PGE levels rise in the fetus and intercaruncular endometrium, but PGE secretion into the maternal circulation is not enhanced. A role for PGF and PGE in fetal, placental and uterine growth is suggested; placental and uterine endocrine function may also be targets. PMID- 4034994 TI - [Construction of the self]. PMID- 4034996 TI - [Current problems of psychoanalytic psychosomatics]. PMID- 4034995 TI - [Integration of self psychology and psychoanalysis on developmental psychologic principles. Demonstrated by the case of Louisa A. by P. Tolpin]. PMID- 4034997 TI - [Homosexuality and psychoanalysis]. PMID- 4034998 TI - Concomitant boost radiotherapy for advanced squamous cell carcinoma of the head and neck. AB - The concomitant boost technique is a variant of accelerated fractionation whereby the boost is delivered as a second daily fraction during the basic treatment course to reduce the total duration of treatment. From April 1972 through June 1983, 53 patients with advanced squamous cell carcinoma of various sites in the head and neck region were treated for cure at U.T. M. D. Anderson Hospital with this technique. In 12 patients, the concomitant boost was used because of rapid recurrence following surgical resection either before or after initiation of planned postoperative radiotherapy; the remaining patients had rapidly growing untreated or recurrent disease in the primary site, neck, or both. In most cases, the concomitant boost was delivered in fractions of 120-150 cGy, separated by 3-6 h from the basic daily treatment of 180-200 cGy. The boost treatments were given 2-3 times a week for 3-5 weeks, delivering an average of about 17 Gy in 12 fractions. Two different treatment techniques were used. Patients with predominantly neck disease (30) were treated with glancing AP and PA fields or with appositional electron beam portals to spare the mucous membranes, while those with advanced or rapidly progressive primary lesions, with or without nodal disease (23), received their concomitant boost through lateral photon or high energy electron beams to include the primary tumor site. As expected, the acute mucosal reactions were most severe in the latter group, but only three patients required interruption of treatment because of severe mucositis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4034999 TI - Advanced carcinoma of the nasopharynx. 2. Pattern of failure in 256 patients. AB - Of 256 patients with advanced carcinoma of the nasopharynx, 82% presented with Stage IV disease. The 5-year survival was 15% with 83% failing within 2 years. Prognosis was related to stage (p less than 0.03), neck status (p less than 0.03), initial performance status (p less than 0.001) and radiation dose (p less than 0.003). With no pathological neck glands (N0), less than 5% failed radiotherapy. Overall, 36% had distant metastases, correlating with the N Stage (p less than 0.001) but not with the T Stage. The most frequent site of metastasis was lung, then bone and liver. Radical neck dissection failed to increase tumor control, contributing to three fatal complications. New radiotherapeutic regimens have so far failed to substantially improve the results. PMID- 4035000 TI - Results of radiotherapy in carcinoma of cervix stages I and II: the impact of involvement of endocervix. AB - The results of radiotherapy in carcinoma of the cervix stages I and II at the University of Missouri-Columbia (UMC) in the period between 1975 and 1980 were analyzed. The failure rate was 13/58 (22.4%). While the failure was 8% (3/36) in ectocervical cancer it was 45% (10/22) in endocervical cancer. The difference was statistically significant to a p value of 0.001. Ten of 13 failure cases (77%) had involvement of the endocervix. In endocervical carcinoma 7 of 10 (70%) of the failure cases had recurrence in para-aortic or supraclavicular nodes. The impact of age, differentiation and hemoglobin level was examined. PMID- 4035001 TI - Survival curves after X-ray and heat treatments for melanoma cells derived directly from surgical specimens of tumours in man. AB - X-ray and heat survival curves were established for melanoma cells derived directly from surgical specimens of tumours in man by using the Courtenay soft agar colony assay. The plating efficiency for 11 of the 14 melanomas studied was sufficiently high (PE = 0.3-58%) to measure cell survival over at least two decades. Experiments repeated with cells stored in liquid nitrogen showed that the survival assay gave highly reproducible results. The melanomas exhibited individual and characteristic survival curves whether exposed to radiation or heat (43.5 degrees C). The Do-values were in the ranges 0.63-1.66 Gy (X-rays) and 33-58 min (heat). The survival curves were similar to those reported previously for human melanoma xenografts. The radiation sensitivity of the cells was not correlated to the heat sensitivity. Since the melanomas appeared to be very heterogeneous in radiation response in vitro as melanomas are known to be clinically, it is suggested that melanomas may be suitable for prospective studies aimed at establishing whether clinical radioresponsiveness somehow is related to in vitro survival curve parameters. PMID- 4035002 TI - Testicular seminoma: analysis of treatment and failure for stage II disease. AB - Seventy-three patients with seminoma testis stage II have been retrospectively analyzed with regard to prognostic factors and value of prophylactic mediastinal irradiation and chemotherapy. Although survival differences were seen between stage IIa, IIb and IIc, these were not statistically significant. Neither was there a significant difference between IIc patients with tumors greater than 10 cm and less than 10 cm in diameter. The incidence of HCG-producing seminomas in the present series was 16%. No significant difference in survival nor relapse rate was found between HCG-producing and HCG-non-producing seminomas. Prophylactic mediastinal irradiation did not influence the survival nor the relapse rate and may therefore be omitted. In the present series there was no significant improvement neither in relapse rate nor survival in patients receiving pre-irradiation chemotherapy. However, the total number of patients is small and optimal pre-irradiation chemotherapy still have to be defined. PMID- 4035003 TI - Some aspects on validity of breast cancer, pancreatic cancer and lung cancer registration in Swedish official statistics. AB - From the Regional Cancer Register of Stockholm County and the Swedish Cause-of Death Register, a total of 1445 individuals were selected. The patients had died in 1978 and were recorded with cancer of breast, pancreas or lung in either (or both) register. Inter-register discordance in regard to diagnostic information was found in 411 cases. Clinical records were retrospectively studied in order to establish the correct diagnosis. In breast cancer, most of the discordance was explained by the numerous deaths from intercurrent causes, though some underestimation of breast cancer as cause of death was noted (5%). Several incorrect entries of pancreas and lung cancer were found in the Cause-of-Death Register, due to inclusion of metastatic disease as primary tumour or non alteration of the death certificate when a subsequent autopsy showed another diagnosis. In the Cancer Register, few diagnoses of pancreas and lung cancer were found to be incorrect. On the other hand, the register showed a slight undernotification of these tumour types. Routine alteration of death certificates when autopsy gives results differing from the clinical diagnosis and information to doctors concerning the aims, routines and coding procedures at the Cancer and Cause-of-Death Registries, presumably would enhance the accuracy of the registers' statistics. PMID- 4035005 TI - The influence of overall treatment time on renal injury after multifraction irradiation. AB - The influence of overall treatment time on the radiation response of the mouse kidney was studied in an experiment in which 16 fractions were administered either evenly distributed over 20, 40 or 80 days, or as a split course (8 F/3 days; 74 days rest; 8 F/3 days). Urine output and an isotope assay of glomerular filtration were used to test the mice sequentially. The data were used both to obtain dose-response curves and also to determine the latent period before a chosen level of injury was expressed functionally. Prolonging the overall time from 20 to 80 days increased the isoeffect dose by 2-5 Gy (4-9%) for the isotope assay, and by 4-9 Gy (7-18%) for the urine output assay. This additional recovery as the interval between fractions was prolonged from 1 to 5 days is consistent with slow repair and can be expressed as a small "T" exponent of 0.02-0.12. (One analysis gave a result consistent with negative repair, but the errors on this result were unusually wide.) When the radiation was given as a split course, at the rate of 2 fractions per day, with a large gap of 10.5 weeks between courses, there was no additional sparing compared with 16 fractions over 20 days. This indicates that any sparing that might have resulted from slow repair or stimulated repopulation in the gap has been counterbalanced by having less time for repair of sublethal injury when intervals of 6-12 h are used instead of 24-48 h. Clearly no great increase in the tolerance dose for mouse kidney resulted from the split course. PMID- 4035004 TI - Patterns of cell loss and repopulation in irradiated cultures of plateau phase C3H 10T 1/2 cells. AB - Patterns of cell loss and repopulation were studied in plateau phase cultures of slowly-cycling, contact-inhibited C3H 10T1/2 mouse fibroblasts following large single, and multiple small doses of 137Cs-gamma rays. A progressive, dose independent cell loss was apparent within days after irradiation with large single doses, and similar patterns of loss were observed following the start of multifraction irradiations. This progressive cell loss culminated in the loss of integrity of the monolayer of cells, a loss of contact-inhibition, and therefore, an increased rate of cell division. The time of onset of measurable repopulation, and the time required to completely repopulate a culture varied with the number of clonogenic cells present at the time of breakdown of the monolayer. For cultures receiving multiple irradiations over time periods greater than those required for breakdown of the monolayer, repopulation began to occur during treatment, and its rate varied with the average dose per fraction being delivered. Thus, repopulation did not start immediately after the start of irradiation, but needed a triggering event, in this case, a decrease to a critical level in the cell density. Once initiated, repopulation was able to decrease or even eliminate the effectiveness of subsequent doses in reducing the number of viable cells per culture. To the extent that the responses of slowly cycling, contact-inhibited cells in vitro can be applied to interpret the radiation responses of cell populations in vivo, these results further support the notion that it may be necessary, in some cases, to account for an increasing contribution from repopulation with increasing overall treatment time in dose fractionation isoeffect formulae used for predicting tissue tolerances or tumor control. PMID- 4035006 TI - Identification by specific radioimmunoassay of two novel peptides derived from the C-terminus of porcine preprogastrin. AB - A radioimmunoassay has been developed using antibodies to a synthetic analogue of the C-terminal hexapeptide sequence of the porcine gastrin precursor. Boiling water extracts of porcine antral mucosa contained immunoreactive material that diluted in parallel with standard peptide. Concentrations of immunoreactivity were 5.5 +/- 0.8 nmol X g-1 (mean +/- S.E.M.) in antral mucosa and were closely similar to those of C-terminal heptadecapeptide gastrin immunoreactivity (5.0 +/- 0.6 nmol X g-1). Approximately 30-fold lower concentrations were found in porcine duodenum. A similar distribution was found in ferret, but human, rat and chicken antrum did not contain significant quantities of immunoreactivity. Gel filtration of porcine antral extracts on Sephadex G-50 revealed a single peak of immunoreactivity eluting in a similar position to G17, but on anion-exchange chromatography two peaks of immunoreactive material were separated. These also differed in their retention time on reverse phase HPLC. Both peptides are probably derived by tryptic cleavage at the C-terminus of porcine preprogastrin. No evidence was found to suggest that there are significant quantities of unprocessed preprogastrin in hog antral mucosa. The precise chemical difference between the two immunoreactive peptides identified here remains to be established; together, however, they provide specific markers for progastrin synthesis. PMID- 4035007 TI - Rat immunoreactive cholecystokinin (CCK): characterization using two chromatographic techniques. AB - Acid and neutral extracts of rat cerebral cortex and upper small intestine were prepared and the endogenous concentrations of cholecystokinin-like immunoreactivity (CCK-LI) measured by three new CCK-specific radioimmunoassays. The characterization of the immunoreactive CCK molecular forms was undertaken using gel permeation chromatography in the presence of 6 M urea to minimise problems relating to peptide adsorption or aggregation. Reverse-phase high performance liquid chromatography (HPLC) was also performed on the rat tissue extracts. Rat cortex contained 268 +/- 12 pmol/g CCK-LI, and over 90% resembled the sulphated CCK-8, which was preferentially extracted at neutral pH. In contrast, the rat upper small intestine (97 +/- 8 pmol/g of CCK-LI) contained less than 20% CCK-8, the majority of immunoreactive CCK being of larger molecular size and being preferentially extracted at acid pH. In the small intestine the predominant molecular form(s) was intermediate in size between CCK-33 and CCK-8. Large amounts of CCK-33 and of a molecular form larger than CCK-33 were also detected. It is concluded that post-translational cleavage of CCK differs in rat brain and gut. PMID- 4035008 TI - Vasopressin pressor antagonist injected centrally reverses behavioral effects of peripheral injection of vasopressin, but only at doses that reverse increase in blood pressure. AB - Previous work in rats (Ader, R. and De Wied, D., Psychon. Sci., 29 (1972) 46-48) has established that subcutaneously (s.c.) injected arginine vasopressin (AVP) prolongs extinction of active avoidance and that this effect could be prevented by pretreatment with the vasopressin antagonist analog [1-deaminopenicillamine, 2 (O-methyl)tyrosine]-beta-arginine vasopressin (dPtyr(Me)AVP). The purpose of the present study was to determine if peripherally administered AVP acts via a peripheral blood pressure effect or by a direct action in the central nervous system. We therefore tested the effects of the antagonist injected intracerebroventricularly (i.c.v.) on the prolongation of active avoidance and on blood pressure effects of s.c. injected AVP. The antagonist (i.c.v.) blocked the behavioral effects of systemically injected AVP only at dose sufficient to block the peripherally mediated pressor response of systemically administered AVP. The results show that peripherally injected AVP acts on peripheral systems and support our hypothesis that the peripheral visceral action of AVP contributed significantly to its behavioral action. PMID- 4035009 TI - [Radioactive and stable cobalt concentrations in mussel in Kyushu islands, Japan]. AB - Two kinds of mussel, Septifer virgatus and Mytilus edulis, were collected from Kyushu island, Japan, in order to elucidate a background level of 60Co, which is one of the most significant radionuclide for environmental monitoring around a nuclear power plant. The mussels were collected from 7 locations in 1983 and classified 2 or 3 groups depending on their shell size at each location. Activities of 60Co were measured by a low-background beta counter after purified by means of chemical separation and electrodeposition. Stable cobalt concentrations were determined by colorimetric method. The concentrations of cobalt in Septifer virgatus are one order higher level than that in Mytilus edulis. There are not so large difference in cobalt content depending on shell size so long as comparing them at the same location. The radioactivities in mussels show the same trend as stable cobalt. It has become apparent that Septifer virgatus has a tendency to concentrate cobalt with growing but Mytilus edulis is opposite. The cobalt-60 introduced to sea from nuclear explosions seems to be relatively constant in coastal seawater since specific activities are distributed in a narrow range in spite of kind, shell size and location. PMID- 4035010 TI - [Measurement of neutrons from an electron accelerator by rem-counter]. AB - In the measurement of neutrons from the medical electron accelerator by a rem counter, two problems disturb accurate measurements. One is the pile-up of signals produced by X-rays during each X-ray burst and the other is the increased counting loss caused by bunched nature of yielded neutrons. The time spectrum of neutrons measured by the rem counter 2202 D (manufactured by Studsvik) rises up to a maximum value by about 20 microseconds and then falls down exponentially with a time constant of about 90 microseconds. On the other hand, that of X-rays is roughly rectangular with several microseconds width. A time discriminating system was prepared to be combined with the rem counter, which was triggered by leading edge of electron beam pulses, rejected pile-up signals due to X-ray bursts, and counted pulses of neutrons in a specified time window. The system discriminated the pile-up enough to measure neutrons at a X-ray dose rate of at least 30 mGy/h. Nonparalyzable counting loss correction was practicable upto about 10 mSv/h for the beam pulse rate of 85 Hz, in which the dead time of the rem counter was estimated as 4 microseconds. PMID- 4035011 TI - [Score judgment method of B type hepatitis associated antigen and antibody by radioimmunoassay kit--HBe antigen and anti-HBe antibody]. PMID- 4035012 TI - [Basic evaluation of a magnetic digoxin radioimmunoassay kit]. PMID- 4035013 TI - [White and black in nuclear magnetic resonance (NMR). Impulse sequences and their significance in the NMR image]. AB - In order to understand how pulse sequences affect what is black and what is white in Nuclear Magnetic Resonance (NMR) images, the tissue parameters (proton density; relaxation times T1 and T2) are related to the operator selectable controls (type of pulse sequence; repetition time TR; interpulse delay TI; echo delay TE). The pulse sequences "Saturation Recovery"; "Inversion Recovery"; "Spin Echo" are discussed. The authors also analyze the effect of flowing blood on NMR images. PMID- 4035014 TI - [The role of adrenal computerized tomography in endocrinopathies. Cushing's syndrome]. AB - A comparison was made between the adrenal or hypophyseal histology and the CT finding of adrenal glands in 18 Cushing patients in an assessment of CT as a preliminary screening measure prior to hormone studies for the detection of subjects with adrenal tumours, and hence candidates for adrenalectomy. The CT finding were: 8 tumours (7 adenomas and 1 carcinoma), 5 hyperplasia, 5 NAD. All the adrenal tumours (diameter 18-69 mm) were correctly identified. The only distinctive feature of the carcinoma was its size. A CT diagnosis of adrenal tumour can be regarded as conclusive. Pictures indicative of hyperplasia or absence of alterations, however, must be supplemented by hormone tests and (if necessary) CT of the hypophysis. PMID- 4035015 TI - [The role of adrenal computerized tomography in endocrinopathies. Primary hyperaldosteronism]. AB - A review was made of the CT findings in a series of 15 patients with a clinical diagnosis of primary hyperaldosteronism. An adrenal tumour (diameter 11-68 mm) was observed in 13 cases. No adrenal involvement was noted in the other two. The initial diagnosis was confirmed either histologically or by means of a thorough clinical and instrumental follow-up in all 15 cases. High-resolution CT may thus be proposed as an initial examination in the diagnosis of primary aldosteronism. Its efficiency is such that venous sampling can be restricted to doubtful or negative cases. PMID- 4035016 TI - [Computerized tomography in the staging of bronchogenic carcinoma. Critical evaluation of 91 cases]. AB - In reviewing 91 cases of bronchogenic carcinoma, traditional radiology (TR) and CT patterns were compared versus surgical/pathologic findings. CT always gave clearer assessment of the mediastinum and thoracic wall invasion. In the evaluation of metastatic spread to hilar and mediastinal lymph nodes the false negative rate was higher with TR than with CT; on the other hand, there was a higher false positive rate with CT. The advantage of CT in the staging of bronchogenic carcinoma is verified and a rationalized flow-chart which includes TR, endoscopy, CT and mediastinoscopy is suggested. PMID- 4035017 TI - [Crystalline calcium pyrophosphate dehydrate deposit disease]. AB - Radiographic features of calcium pyrophosphate dihydrate (CPPD) crystal deposition disease are outlined in an investigation of 32 patients, with definite or probable disease (according to the diagnostic criteria previously utilized by McCarty). The crystal deposits within fibro- and hyaline cartilage (chondrocalcinosis) may produce an acute synovitis (pseudogout syndrome), and in some patients a radiographically distinctive degenerative arthropathy (pyrophosphate arthropathy). These abnormalities are most frequent in the knee, wrist and symphysis pubis, but often other joints may be affected. Although the alterations superficially resemble osteoarthritis, they are more severe and progressive (Charcot-like joint). PMID- 4035019 TI - [A method for rapid and precise positioning of screens in the treatment using irregularly shaped fields]. PMID- 4035018 TI - [Experimental dosimetric comparison between single tomography and multiple simultaneous tomography with Synchroplan in clinical practice]. AB - Reference is made to a dosimetric comparison between single tomography and simultaneous multiple tomography with Synchroplan in 10 patients subjected to nefroangiotomography. Data from several thermoluminescence dosimeters placed on different parts of the body were used in a careful statistical analysis that showed the absence of significant differences in absorbed dose in function of constitutional habitus. It was also found that the dose absorbed for 6 tomograms of the renal cavities in single tomography was about 4 times higher than with the Synchroplan (using a previously experimented set of high-sensitivity intensifying screens), which provides 6 tomograms in the same dynamic phase at different levels for the same exposure. PMID- 4035020 TI - [Castelman's tumor of the mesentery]. PMID- 4035021 TI - [Catheter brachial plexus anesthesia for intra- and postoperative pain control. Plasma concentrations and analgesia interval in the use of bupivacaine]. AB - In 15 orthopedic patients, undergoing plastic surgery of the upper extremity (elbow, forearm, hand) we studied plasma levels and pain free intervals, when performing catheter axillary plexus block with 0.5% and 0.25% bupivacaine as postoperative analgetic agent respectively. 30 minutes after injection of 40 ml of 0.5% bupivacaine maximum plasma levels were reached (means = 1.46 micrograms/ml), followed by a constant but slow decrease to 1 microgram/ml approximately after 2 h. 11.5 h (mean) after brachial plexus block there was a need for reinjection of local anesthetic solution for postoperative pain control. The pain free interval after 30 ml of 0.25% bupivacaine lasted 10.5 hours on the average. The 'top-up-dose' of 75 mg approximately equal to 30 ml of 0.25% bupicavaine caused only a small rise in plasma levels up to 0.6 micrograms/ml. Catheter brachial plexus block with bupivacaine is an appropriate procedure for both intra- and postoperative pain relief, especially in re-implantation surgery of the upper limb. PMID- 4035022 TI - [Thoracic peridural opiate-analgesia]. AB - In patients with cancer pain caused by tumours in the upper thorax, shoulder or neck area the thoracic approach for peridural opiate analgesia is indicated. The thoracic puncture technique is more difficult and the possible complications are more serious than puncture in the lumbar area; it therefore belongs, as pain therapy generally, in the hands of an anaesthesiologist experienced in regional anaesthesia. In selecting the puncture level appropriate to the site of pain, it is necessary to take account of the fact that the vertebral interspace does not correspond with the spinal segment. Only thus can an optimal analgetic effect with a minimal dose b assured. PMID- 4035023 TI - [A case of transverse spinal cord syndrome following contamination of a peridural catheter]. AB - Two weeks after removal of a peridural catheter a transverse lesion of the cord with paraplegia developed. At operation a paravertebral abscess, osteomyelitis of the lamina L2 and L3, and epidural abscess, a phlegmonous duritis and myelitis of the conus-cauda region by transmigration was found. The catheter had been in position for four days. The infection was caused by staphylococcus epidermidis. After laminectomy L2 and L3 as well as local and systemic application of antibiotics, according to the results of sensitivity tests, neurological deficits disappeared nearly completely. PMID- 4035024 TI - [Treatment of septic or non-septic diaphyseal pseudoarthroses by Ilizarov's monofocal compression method]. AB - The treatment of non-union of long bones is one of the best indications for the use of Ilizarov external fixation. The method is somewhat expensive but without risk. In 20 patients, use of the technique achieved healing in cases in which traditional methods such as bone grafts, plates or other types of external fixator had failed. The main advantages are avoidance of further vascular disturbance, a stable and elastic fixation and the possibility of early weight bearing with consequent compression. PMID- 4035025 TI - [Postoperative infection of fractures of the femoral diaphysis treated by osteosynthesis. Long-term outcome]. AB - The authors have operated on 284 simple fractures, complicated by 12 post operative infections (4.2 per cent) and 43 compound fractures, complicated by four infections (9.3 per cent). All the fractures were treated by plating. Thirteen of the infected cases have received long-term follow-up - ten after simple fractures and three after compound fractures. Nine out of the ten cases following simple fractures have healed, eight retaining the plate until consolidation and two being considered as infected non-unions. One of these two healed secondarily after fresh fixation and the other is still draining after a second operation, but has united. Two out of the four cases following compound fractures have already healed. The two others were considered as infected non union and healed after fresh fixation. It is concluded that infection after fracture of the femoral shaft is a serious complication, but healing can be obtained in almost all cases. No amputation was needed. PMID- 4035026 TI - [Treatment of acute pyogenic arthritis of major joints of the limbs]. AB - The authors have treated 52 cases of septic arthritis of major joints. When aspiration contain an opaque fluid, conservative treatment with antibiotic therapy and immobilisation obtained healing in half of the patients. Surgical lavage of the joint was needed on 21 occasions with healing in 15. Synovectomy was performed in 8 cases and was indicated only at the stage of pyogenic synovitis before the development of pyogenic arthritis. When the latter stage was reached, arthrodesis was indicated. It was performed primarily on 6 occasions and secondarily once. Seven patients died. The average age was seventy years. The importance of early treatment is stressed. PMID- 4035027 TI - [Surgical treatment of flail chest by sliding staples]. AB - The authors have compared the results obtained in two series of patients with flail chests treated by internal fixation. In the first series of 36 patients, Judet rib staples were used. The average time of artificial ventilation was 5.8 days. In the second series of 43 patients, gliding staples were used. The average time of artificial ventilation was only 2.6 days, a significant reduction. Thanks to this new technique, the indications for artificial ventilation in the treatment of flail chests have been reduced from 47 per cent to 33 per cent. The technique of fixation has also been used in seven cases of operative treatment of funnel chests. In five other cases it has been used to reinforce plastic mesh inserted after extensive resection for malignant tumour. PMID- 4035028 TI - [Functional results of tibio-tarsal arthrodeses. Apropos of 52 reviewed cases]. AB - Fifty-two patients with ankle arthrodesis were reviewed after an average follow up of 7 years with a range between 2 and 22 years. Two-thirds of the patients had good results and 1 in 4 had fair results. In 4 cases there were bad results. Thirty-seven patients could walk without any limitation thanks to mobility of the mid-tarsal joint. Most of the patients developed radiological arthrosis of the subtalar joint with limited movement in 29 instances. In contrast, hypermobility of the mid-tarsal joint was present in almost half of the cases. Good functional results were related to the preservation of mobility in the subtalar and mid tarsal joints. The time required to obtain a good functional result was about one and-a-half years. After this the results were stable, provided that the ankle fusion was in a good position. Most of the poor results were related to arthrosis of the sub-talar joint or trophic changes. Secondary extension of fusion to other joints was deceptive. It is concluded that combined arthrodesis of the tibio talar and sub-talar joints should be done only in cases of severe arthrosis. In other cases, the mobility of the sub-talar and mid-tarsal joints should be preserved. PMID- 4035029 TI - [Bilateral luxation of L5-S1. Apropos of a case reduced and fixed at the 120th day]. AB - A case of pure anterior lumbosacral dislocation without fracture of the posterior arch has been seen by the authors. The patient was a woman who was six months pregnant at the time of injury. The dislocation was not recognised at first. Four months later, after delivery, function was poor. The displacement was reduced surgically and fixed by plates and screws using a posterior approach. PMID- 4035030 TI - [A case of bone lipoma of the femur head]. AB - A case of intra-osseous lipoma of the upper femur is reported. A review of the literature shows that this lesion is rare, only about 33 cases having been published. The radiological appearance is that of a fibroma. The diagnosis is made at the time of surgery which reveals the presence of fat in a large cavity. Curettage and bone graft resulted in healing. PMID- 4035031 TI - [Costal osteosynthesis by plating]. AB - The authors have utilised rib stabilization by plating in five patients. The sites at which such operations are indicated are discussed. The procedure is performed with the patient prone or in the lateral position. A solid fixation was always achieved. This surgical procedure was performed - not only on flail chests, but also on potentially unstable lesions. PMID- 4035032 TI - [Use of total conjugated bile acids in alcoholics without evidence of hepatopathy]. PMID- 4035033 TI - [Markers of hepatitis B virus in an oncology unit]. PMID- 4035034 TI - [2 cases of dysplastic gangliocytoma of the cerebellum]. PMID- 4035035 TI - [Motor disorders of the extremities in herpes zoster. Presentation of 4 cases]. PMID- 4035036 TI - [Acute liver failure and Wilson's disease]. PMID- 4035037 TI - [Hyperparathyroidism. Report of a case of primary hyperparathyroidism caused by an adenoma]. PMID- 4035038 TI - [Gardner syndrome: study of a case]. PMID- 4035039 TI - [Overdose of biguanides]. PMID- 4035040 TI - [Gammagraphic localization of pheochromocytoma using 131I-meta iodobenzoylguanidine (131I-MIBG)]. PMID- 4035041 TI - [Carpal tunnel syndrome caused by oral contraceptives]. PMID- 4035042 TI - [Capillary microscopy of the nail fold in Raynaud's phenomenon. Use in the early diagnosis of scleroderma]. PMID- 4035043 TI - [Ergometric validation of a questionnaire on the physical activity in 2 Swiss towns]. AB - A questionnaire concerning physical activity used in the National Research Program No. 1A (PNR 1A) was evaluated by using a physical fitness test on an ergometric bicycle. The values of maximum oxygen consumption correspond to different classes of physical activity set up according to the questionnaire (comparison of groups statistically significant). In addition, it appears that maximal oxygen consumption is in direct relation to the intensity of physical activity during leisure hours, whilst the degree of activity connected with professional or household duties is of very little importance. PMID- 4035044 TI - [Bacterial contamination of the air in different operating rooms]. AB - Bacteria air samples were taken in the operating rooms, with no people present, to specify the level of air contamination and suggest bacteriological standards for different operating rooms. In the first step of this study, for 5 months the air contamination mean value of operating rooms, ventilated at 15 changes/hour was 18.5 Cfu/m3 +/- 1.9. In the second part of the study, during two years, 1 381 air samples were taken in 8 different operating rooms. The mean values of air contamination range from 1.4 Cfu/m3 in a Charnley isolator system to 121 Cfu/m3 in an operating room ventilated at 7.5 changes per hour. As a general rule, the airborne contamination is more significant in the oldest operating rooms than in the new one with filtrated air. The variations observed between 1981 and 1982 are explained by technical modifications of the system or progress in control of operating room conditions. Measurements of the bacterial contamination of the air give useful informations, but it is however better to ensure that the specifications for volume air supply and positive air pressure in the operating theatres are being fulfilled. The airborne bacterial concentration in a modern ventilated operating room should not exceed 30 Cfu/m3. PMID- 4035045 TI - [The search for Yersinia enterocolitica in vegetables treated by a cold line in school cafeterias in Montpellier]. AB - From 134 samples of raw or cooked vegetables taken in two points of a cold line we isolated 19 strains of Yersinia enterocolitica, 3 of Y. intermedia 3 of Y. kristensenii. None of them belongs to serotypes usually pathogenic for man. The raw vegetables are most contaminated. Y. kristensenii and Y. intermedia were isolated especially from samples of green salad. The used method was a cold enrichment at 4 degrees C followed by a potassium hydroxyde treatment. The activity of 16 antimicrobial drugs was studied by the disk diffusion test at 28 degrees C. All strains were sensitive to aminoglycosides, minocycline, colistine and cotrimoxazole. The results obtained with chloramphenicol and beta-lactam antibiotics vary in terms of species and/or biotypes. PMID- 4035046 TI - [Seasonal anthropometric variations in adults of 2 different West African populations]. AB - Results of nutritional surveys carried out during the wet and dry seasons in the South of Mali and the North of Senegal (Ferlo) reveal that adults in both areas experience seasonal weight variations of about 4%. These variations are related to the regular occurrence of food shortages during the rainy season. The circumstances in which these food shortages occur are not the same in the two communities: while the nomadic herders of Ferlo can significantly reduce energy outlay by resting during the rainy period, the Malian farmers, on the contrary, must work harder because their agricultural tasks are most demanding in this season. In conclusion, we stress the need to take this phenomenon into account in agricultural development projects and to overcome shortages provoked by the shift in peasants' habits from subsistence agriculture to cash crops. PMID- 4035047 TI - Prevention of coronary heart disease: priorities for action and further research. PMID- 4035048 TI - [Evolution of tobacco consumption in 2 towns with intervention programs and 2 control towns in Switzerland]. AB - The National Research Program 1 A on "Primary Prevention of cardiovascular disease in Switzerland' was designed to determine whether community health education can reduce cardiovascular risk factors in the population. Two communities (12,000 inhabitants each) in the French speaking and two (16,000 inhabitants each) in the German speaking part of the country were selected either for intervention or comparison. Following baseline screening in 1977 (stratified random samples) and the community intervention program (1978-1980), a final assessment on the initial participants was performed at the end of 1980. Amongst the regular smokers, 26,2% stopped during this period in the intervention communities whereas 18,1% did so in the reference cities. 4,7% of non-smokers began to smoke during the same period in the intervention communities whereas 7,8% did so in the reference cities. Plasma thiocyanate measurement suggested reliable answers on smoking status. These results suggest that community health education may be effective in preventing harmful health consequence of smoking. PMID- 4035049 TI - [The influence of family environment on the evolution of tobacco consumption in 2 trial towns and 2 control towns in Switzerland]. AB - As part of a study on cardiovascular risk factor modification in four Swiss cities (National Research Program 1A, "Primary Prevention of Cardiovascular Disease in Switzerland") between 1977 and 1981, the influence of family members on changes in tobacco consumption was investigated. In this study there were two intervention cities, with a community health education program, and two reference cities. The net decrease of regular smokers was significantly more important in the intervention cities (-3.6%, p less than 0.05), however there was no significantly different pattern for family members. In contrast, there was a significant influence among adult family members both for the decrease (p = 0.0001) and the increase (p less than 0.005) in tobacco consumption. PMID- 4035050 TI - [The evolution of plasma cholesterol in 2 towns with intervention programs and 2 control towns in Switzerland]. AB - As part of the "National Research Program 1A" (PNR 1A) on the prevention of cardiovascular disease, a study was made of changes in blood cholesterol levels in the populations of two intervention cities (Nyon and Aarau) with a community health education program, and two reference cities (Vevey and Solothurn). A fall in cholesterol levels was noted in both the intervention and reference cities, with no difference in between the cities. However, a clear, statistically significant (p less than 0.05) fall was recorded in a group of women who participated in prevention activities concerned with nutrition, in comparison with a group of non-participating women, in the two intervention cities. PMID- 4035051 TI - Transport of calcium, magnesium and strontium by human serum proteins. AB - The association constant and the maximal binding capacity for calcium, magnesium and strontium to human serum proteins were determined using a wide concentration range by a dialysis technique. The association curves are similar for these elements. Each curve may be subdivided in three parts: the first would correspond to the subfraction tightly bound to protein, the second one shows a linear design implying the association of the element to different binding points which have the same association constant, and the third part shows the saturation of proteins, which is achieved by alkaline-earth concentration about 9 times higher than the physiological ones. PMID- 4035052 TI - [Effects of thyroidectomy and submaxillary sialoadenectomy on physiological parameters in the female rat]. AB - The effects of interaction of the thyroid function with the submaxillary glands on the female rat, on the body growth, weight evolution of adrenal glands, ovary and parotid glands, puberty onset, estrous cycle, fertility, gestation and offspring size, plasmatic levels of glucose, glucagon, Na+, K+ and total protein have been studied. The effects of sialadenectomy and thyroid function are both independent in all parameters, except in ovary growth, which is depressed by thyroid function when submaxillary glands are removed, and in circulating glucose, since sialadenectomy stabilizes to hypoglycemia which results from thyroidectomy. PMID- 4035053 TI - [Hypotension and diffusion of Rb-86 in the rat brain]. AB - Studies on the permeability of potassium at the blood-brain barrier of rats show that, under normal conditions, the concentration of this ion is kept constant although wide variations in plasma are present. 86Rb has been utilized as an analog of K+. The permeability constant for control animals (arterial blood pressure of 100 +/- 3 mmHg), has been determined in 0.926 +/- 0.02 ml X g-1 X h-1 (brain cortex), and 1.107 +/- 0.12 ml X g-1 X h-1 (cerebellum). The permeability constant for hypotensive animals (arterial blood pressure of 40 +/- 5 mmHg), has been determined in 0.473 +/- 0.03 ml X g-1 X h-1 (brain cortex), and 0.608 +/- 0.06 ml X g-1 X h-1 (cerebellum). During hypotension there is a marked decrease in the permeability constant of 86Rb at the blood-brain barrier of rats. PMID- 4035054 TI - Oil-stop method as an alternative to filtration for transport studies on plasma membrane vesicles. A preliminary report. AB - The oil-stop procedure applied in transport studies on whole cells was adapted for isolated plasma membrane vesicles. The advantages of the proposed technique with respect to the commonly used filtration method are the reduction of the period of the termination step, the increase in the allowed membrane content of the samples and the absence of the leakage of substrates from the intravesicular space. PMID- 4035055 TI - [Inhibition of macrophage phagocytic activity by selective sensitization to alloantigens of the H-2 system]. AB - The action exerted by selective sensitizations to alloantigens coded by the Major Histocompatibility System of the mouse, H-2, on the phagocytic ability of the mouse peritoneal macrophages has been studied. The results suggest that when immunizations are performed between completely incompatible animals for the H-2k haplotype, after the third immunization the total number of macrophages able to carry out phagocytosis decreases very significantly. When the incompatibilities, however, are due to the left half of the H-2 system or to minor histocompatibility antigens, such an inhibition does not appear. PMID- 4035056 TI - [Proliferative response of murine lymphocytes caused by the activity of amphiphilic molecules from Propionibacterium acnes]. AB - Splenic lymphocytes from mice treated with Propionibacterium acnes cells as well as with their cell walls were found to be variably active on the lymphoproliferative responsiveness. Furthermore, the effect of these bacterial agents on the ex vivo Con A response of the lymphocytes showed a certain stimulation that was higher with oral treatments. In the same conditions the influence of these agents on the LPS lymphocytes stimulation was almost without any statistical significance. In vitro blastogenesis experiments were undertaken in order to elucidate the influence of different amphiphilic molecules from peripheric bacterial structures on the lymphoproliferative response of murine splenocytes. Stimulation rates were also determined as a function of the (3H) thymidine incorporation. Combined effects of mitogens (Con A and LPS) with bacterial amphiphilic molecules were also evaluated as a function of the DNA synthesis variations. All cases resulted in a variable inhibition of the mitogenic response which appeared dose-dependent and more active for associations of Con A and amphiphilic molecules. The most effective intrinsic mitogenic activities were detected with teichoic acids and intracellular polysaccharides. These last molecules without purification, assayed as cytoplasmic fractions, appeared modified in the intensity of their action, depending on their carbohydrate/protein ratios. PMID- 4035057 TI - [Changes in the ovarian structure and fertility of the rat after various ovarian neurectomies]. AB - The changes undergone by the ovary 30 days after different unilateral neurectomies were investigated in 45 rats. Fertility modification was observed in a second group of 40 rats that, after the same neurectomies, were placed with a male for a period of 20 days. The only significant change in the ovarian sympathectomized rats was a decrease in the nuclear area of the luteal cells. In the rats with an additional ovariectomy a significant compensatory hypertrophy appeared in the luteal cells. Vagotomy provoked a significant nuclear hypertrophy in the interstitial and luteal cells, as well as in the corpora lutea. In the cases with contralateral ovariectomy this hypertrophy was considerably reduced. Section of the pelvic splanchnic nerve only produced a decrease of the nuclear size in the luteal cells. Subsequent contralateral ovariectomy was followed by an additional atrophy of the luteal cells and corpora lutea. These results indicate that the parasympathetic system, in normal conditions, plays an inhibitory role, while the sympathetic has a light stimulatory effect, principally on the luteal cells. In relation to fertility, 50% of the neurectomized rats, 75% of the control ones and 100% of the neurectomized and contralaterally ovariectomized rats were found pregnant. The average of the embryos implanted in the uterine horn of the neurectomized ovary was significantly smaller than in the control side. On the contrary, in the ovariectomized rats, especially in the case of sympathectomy, the average of the embryos implanted in the uterine horn of the ovariectomized side was significantly higher than in the control animals. PMID- 4035058 TI - Biochemical changes in testis and ovary of Chrysocoris stolli Wolf. after the application of juvenoid and ecdysterone. AB - The changes in the metabolic status of both testis and ovary of Chrysocoris stolli following the treatment with juvenile hormone analogue (JHa) and ecdysterone were studied. After the exogenous application of JHa in selective dose, total carbohydrate, glycogen, trehalose, cholesterol, ascorbic acid and inorganic phosphorus increased significantly whereas free fatty acid (FFA), phospholipid, total protein, RNA and DNA decreased significantly in comparison to control of both testis and ovary. Total lipid significantly decreased in testis and significantly increased in ovary after JHa injection. The activities of cellular enzymes like alkaline phosphatase, 5' nucleotidase, catalase and peroxidase significantly decreased while acid phosphatase and GPT significantly increased after the JHa application in comparison to control both in testis and ovary. Activities of GOT and general esterase significantly decreased in testis and increased in ovary after JHa application. The exogenous application of ecdysterone also brought about the similar kind of responses as was noticed in case of JHa treatment but these two treatments differed in some cases such as ecdysteroid that produced some results which were just the reverse of what was produced by JHa treatment. The results obtained here were explained in terms of mode of action of these two hormones. PMID- 4035059 TI - [Respiratory function changes in multiple myeloma]. PMID- 4035060 TI - [Plasma cell leukemia: clinical and morphocytochemical aspects in 5 cases]. PMID- 4035061 TI - [Fibrodysplasia of the renal artery. Clinical, histopathologic and angiographic aspects]. PMID- 4035062 TI - [Nuclear magnetic resonance in the morpho-functional study of the kidney]. PMID- 4035063 TI - [Update on the prevention of postoperative venous thromboembolic disease: mini dose heparin]. PMID- 4035064 TI - [The spectrum of myelomas and "senile" myeloma]. PMID- 4035065 TI - [Systemic changes in portal hypertension]. PMID- 4035066 TI - Rationale for perioperative anticancer treatment. PMID- 4035067 TI - Perioperative chemotherapy. Rationale, risk and results. Proceedings of an international symposium, 17/18 March, 1983, Zurich. PMID- 4035068 TI - Surgical intervention and metastasis. AB - Recent findings, briefly summarized here, show that the dissemination of neoplastic cells is an early and continuing process; that individual tumor cells in a malignant tumor possess differing metastatic capacities; and that metastases can arise from specific subpopulations of tumor cells. These findings have considerable implications for the understanding and treatment of systemic malignancies. The underlying cause for the finding that surgical removal of the primary local tumor is often followed by considerably enhanced outgrowth of established micrometastases is not yet understood. The trauma and stress associated with surgical intervention does not of itself seem to constitute a major tumor-promoting component. More likely candidates responsible for enhanced outgrowth of metastases after surgery are the removal of the growth-inhibitory restraint that the primary tumor exerts on disseminated neoplastic cells. PMID- 4035069 TI - The risks of perioperative chemotherapy in large-bowel cancer surgery. PMID- 4035070 TI - Combined-modality treatment with induction chemotherapy in locally advanced squamous cell carcinoma of the oral cavity and oropharynx. PMID- 4035071 TI - Drug selection for perioperative chemotherapy. AB - A wide variety of tumor types can be successfully grown with the clonogenic assay. However, few tumor types perform adequately for routine drug sensitivity testing, e.g., ovarian carcinoma and malignant melanoma. Because of insufficient in vitro growth, the cloning system cannot help substantially in indicating active substances for epidemiologically frequent tumors that usually have a poor prognosis, such as colorectal cancers and non-small cell lung and breast cancers. The degree of in vitro cell kill that would correspond to complete eradication of micrometastases is unknown. The identification of individual patients sensitive to a given antineoplastic agent becomes more difficult as the tumor becomes more refractory to treatment. At this moment, the clonogenic assay appears most promising for trials dealing with the treatment of ovarian adenocarcinoma. PMID- 4035072 TI - Methodological and statistical aspects in perioperative chemotherapy trials. AB - Cancer clinical trials designed to test the value of perioperative chemotherapy present special statistical problems for the investigator. Because chemotherapy must begin within hours of surgery, aspects of the design, conduct, and analysis of such trials are more complex than for many other types of clinical investigations. Special attention must be given to the logistics of patient entry. In some situations, patients may receive a treatment assignment prior to the determination of eligibility or even prior to histological diagnosis of cancer. Design problems may arise when important prognostic factors are not known at the time of randomization. A comparison of perioperative chemotherapy to other, conventionally timed adjuvant chemotherapy requires that adjuvant treatment be purposely delayed for some patients. Because patients enter a perioperative chemotherapy trial before or soon after surgery, the patient population is not the same as that treated in standard adjuvant trials. Thus it is not possible to compare results directly between perioperative and standard adjuvant trials. Analyses of toxicity will include surgical morbidity which would not be seen in conventional adjuvant trials. The analysis of perioperative chemotherapy trials requires care, as many case exclusion factors may make it difficult to determine the true effectiveness of the perioperative treatment plan. Analysis by intent to treat is recommended. These and other statistical and logistic aspects are discussed with reference to the current trial being conducted by the Ludwig Breast Cancer Study Group. PMID- 4035073 TI - Short perioperative versus long-term adjuvant chemotherapy. AB - A single course of cyclophosphamide IV 5 mg/kg daily for 6 days was given immediately after mastectomy to 507 patients (519 randomized controls). The relapse-free rates were significantly increased, and after 16 years the difference was 12%. In a parallel series the same adjuvant course was given 2-4 weeks after mastectomy to 52 patients (58 randomized controls). No effect of this delayed course was found. In a second study a short multidrug course was given to all patients immediately after mastectomy. One-half of the axillary node-positive cases were randomized to continue with IV CMF for 1 year. The preliminary observations show that the prolonged treatment improved the relapse-free rates significantly during the first few years. One year after mastectomy the difference was 10%; after 2 years, 9%; after 3 years, 11%; and after 4 years, 9%. The side-effects of the short course were negligible, but the side-effects of prolonged treatment were considerable and increased with increasing treatment duration. More trials are needed to find the optimum duration of adjuvant chemotherapy. PMID- 4035074 TI - Kinetics of microsomal metabolism of quinidine in rats. AB - Kinetics of in vitro metabolism of quinidine was investigated using rat liver microsomes. Quinidine elimination was capacity limited with apparent Michaelis constant (appKM) of 2.6 microM (about 1.2 mg/L) in liver microsomes from uninduced rats. Phenobarbital (PB) pretreatment caused induction of quinidine metabolism. Formation of all three metabolites important in man, 3 hydroxyquinidine, quinidine N-oxide and quinidine 10,11-dihydrodiol were PB inducible (Vmax increased). To study any direct interaction between PB and quinidine, PB was also added to the microsomal incubate and was found to decrease the rate constant for quinidine metabolism, suggesting inhibition of quinidine metabolism by PB. While, 3-hydroxyquinidine formation was inhibited (Vmax decreased and KM increased), the formation of quinidine N-oxide was activated (Vmax increased). The formation of quinidine 10,11-dihydrodiol, although a minor metabolite in rat, was also inhibited in presence of PB. It is apparent from this study that PB when administered in vivo would act as both inducer and inhibitor of quinidine metabolism. PMID- 4035075 TI - Antinociceptive effect of intracerebroventricularly administered histamine in rats. AB - Intracerebroventricularly (icv) administered histamine produced a dose-related antinociceptive effect in rats, using the rat tail-hot wire technique as the experimental parameter. The H1-receptor agonist, 2-methyl-histamine, given icv, also induced marked antinociception, whereas the H2-receptor agonist, 4 methylhistamine, produced relatively weaker and transient antinociception. Histamine-induced antinociception was significantly inhibited by mepyramine, a H1 receptor antagonist, but not by cimetidine, a H2-receptor antagonist. 5,6 Dihydroxytryptamine, a specific serotonin neuronolytic agent, and p chlorophenylalanine, which selectively inhibits serotonin synthesis, markedly inhibited the antinociceptive effect of histamine, which was also attenuated by naloxone, an antagonist for endogenous opioid receptors, and by dexamethasone, which is known to reduce central endorphin concentrations. On the contrary, the effect of histamine was potentiated by adrenalectomy and by metyrapone, an inhibitor of endogenous corticoid synthesis, which are known to enhance central endorphins. PMID- 4035076 TI - Effects of verapamil and taurine administration on heart taurine and calcium in BIO 14.6 cardiomyopathic hamsters. AB - Administration of either taurine or verapamil raised heart taurine and reduced heart calcium levels in BIO 14.6 hamsters. Combined administration of the two agents magnified both effects. It is suggested that the marked reduction of heart calcium produced by verapamil may be partially mediated through the membrane stabilizing, calcium-modulating actions of taurine at the sarcolemma. PMID- 4035077 TI - The ovarian enzyme catalyzing conversion of 13,14-dihydro-15-ketoprostaglandin F2 alpha to 13,14-dihydroprostaglandin F2 alpha in rats. AB - The preliminary experiments concerning enzymes involved in the production system of 13,14-dihydroprostaglandin F2 alpha (13,14H2-PGF2 alpha) in rat ovary were carried out. The enzyme which converted 13,14-dihydro-15-keto-prostaglandin F2 alpha (15KD-PGF2 alpha) to 13,14H2-PGF2 alpha required NADPH as a cofactor, and the enzyme activity was inhibited by sulfhydryl reagents as well as quercitrin. Thus, the enzyme studied here seems to be a carbonyl reductase possessing SH group(s) in the molecule. PMID- 4035078 TI - Modulation of symmetrical 1,2-dimethylhydrazine (DMH)-induced colon carcinogenesis by isoproterenol (IPR). AB - The modulatory effect of IPR on the initiation and promotion of DMH-induced colon carcinogenesis was investigated using CF-1 young adult female mice. IPR given soon after each of weekly DMH injections inhibited the initiation phase of colon carcinogenesis when the cumulative dose of DMH was small. However, such inhibition was not observed when the cumulative dose of DMH was doubled. Colon neoplasms that developed in spite of IPR treatments seemed to infiltrate the colon wall earlier as compared to those without IPR. On the other hand, IPR did not appear to affect the promotion phase of colon carcinogenesis. PMID- 4035079 TI - 12-O-Tetradecanoyl-phorbol-13-acetate (TPA) induced congenital kidney defects and embryomortality in the CD-1 mouse. AB - CD-1 Mice were treated with daily intraperitoneal injections of 10 or 100 micrograms/kg 12-O-tetradecanoyl-phorbol-13-acetate (TPA) on pregnancy days 8, 9 and 10 or 11, 12 and 13 (early and late organogenesis). By the same regimen, the LD50 for TPA was about 450 micrograms/kg. TPA treatment induced embryomortality, fetal malformation and reduced fetal weight, generally in a dose-related manner. TPA treatment (100 micrograms/kg) was markedly more embryolethal on days 11-15 (68%/litter) than in early organogenesis (18%/litter). Renal malformations were observed in all treatment groups at a low incidence (about 5% of live fetuses) and in no case was the total incidence of malformations greater than 10%. There was little correlation between indications of maternal toxicity and the adverse outcomes of pregnancy, suggesting that TPA has direct embryotoxic effects. The relatively low incidence of anomalies is considered a paradox in light of the potent effects of TPA on cellular processes critical to embryogenesis. PMID- 4035080 TI - Evaluation of topically applied (AET) 2-aminoethyl-iso-thiouronium for radiation protection of the skin. A preliminary study in pigs. AB - AET (Aminoethyl-iso-thiouronium) was applied topically on irradiated pig skin in different vehicles (emulsions and solutions) for testing a protective effect. A simple normal saline solution (200 mg/100 ml) proved to exert the best effect, both macroscopically and histologically. The solution was applied two hours and immediately before the irradiation which consisted of one 2000 rad fraction with a 20 MeV electron beam. A protective effect was noticed only in the superficial epithelial layers, the deeper radiobiological effect remained unaltered. PMID- 4035081 TI - Nonthrombogenic arterial reconstruction. AB - Carboxyl groups of heparin were activated by carbodiimide (EDC) to allow stable covalent binding of heparin to various arterial reconstructions. Ammonium hydroxide treated Human Umbilical Veins Grafts (HUVG) outperform carotid arteries of goat, porcine and canine origin in both heparin loading and stability. In vitro studies reveal that heparin bound HUVG retains its anticoagulative activity, showing promise towards the development of a nonthrombogenic small caliber vascular prosthesis. PMID- 4035082 TI - Effect of acute and chronic exposure to heat on pharmacokinetic parameters of digoxin in rats. AB - Digoxin pharmacokinetic parameters in acute heat-exposed male rats (AHE) maintained for 3 hours at 35 degrees C, and chronic heat-exposed rats (CHE) maintained at 35 degrees C for 4 weeks, were compared to control rats (C) maintained at 22 degrees C. Digoxin concentration in the plasma was measured by radioimmunoassay which gave values similar to thin layer chromatography method. The half life time of digoxin during the elimination phase of the drug (t 1/2 beta) was similar in all three experimental groups (2.8; 2.7; 3.0 hrs) while the values obtained by extrapolation of digoxin plasma concentration to zero time (CpO) was 40% higher in AHE rats and 375% higher in CHE rats than in C rats. The apparent distribution volume of the drug (Vapr) was 40% lower in AHE rats and 80% lower in CHE rats as compared to C rats. PMID- 4035083 TI - The pharmacokinetics of inhaled N2O in children. AB - A new approach is described for the calculation of elimination half-life of inhaled N2O. We generated the elimination rate constant (Ke) by measuring the cumulative fraction of exhaled N2O versus time during induction of anaesthesia with oxygen and nitrous oxide. The amount of N2O which remained in the body at 90% steady-state (X1 90%) was estimated by subtracting the cumulative exhaled N2O from the cumulative inhaled N2O. In young children (age range 4-36 mo, mean 19 mo) the elimination rate constant was significantly higher than in adolescents and young adults (age range 14-20 yr, mean 16.8 yr) (0.14 +/- 0.055/sec and 0.0646 +/- 0.019/sec, respectively) (P = 0.025). Elimination T1/2 was therefore shorter in the young children (6.1 +/- 3.3 vs 11.1 +/- 3 sec) (P less than 0.025). T1/2 was longer (14 +/- 2.6 sec) in children with left to right shunt despite being younger than the adolescents and young adults (age range 3.25-15 yr, mean 9.9). X1 90% was significantly larger in the young children (30 +/- 3% of the administered dose) than in the older children (26.7 +/- 2%) (P less than 0.05). Elimination T1/2 positively correlated with the amount of N2O which remained in the body at 90% steady-state (X1 90%) (r = 0.85, P less than 0.01), suggesting that the distribution of N2O and not its clearance is the main determinant of its elimination T1/2 in normal children. PMID- 4035084 TI - Intestinal uptake of intact maternal lymphocytes by neonatal rats and lambs. AB - Two experiments were conducted using neonatal rats and lambs. The intestinal lumen of neonatal rats was infused with radiolabelled syngeneic lymphocytes, whereas the intestine of lambs was infused with radiolabelled allogeneic maternal lymphocytes. The results of both experiments indicated that radiolabelled cells were absorbed by the intestine as judged by autoradiographic studies of intestinal tissue. Furthermore, in lambs it was possible to show that these cells were transported via the lacteal lymph ducts to the mesenteric lymph nodes. These findings suggest another mechanism by which the lactating ewe may confer immunity to its suckled young. PMID- 4035085 TI - Pharmacokinetics of flunixin meglumine in the cow. AB - Plasma levels of flunixin were measured in heifers after a single intravenous injection (1.1 mg kg-1), using high performance liquid chromatography. Plasma concentration versus time curves were best described by a two compartment model. The distribution phase (alpha) half-life was 0.294 hours, the elimination phase (beta) half-life was 8.12 hours and the volume of distribution was 1050 ml kg-1. PMID- 4035086 TI - Trichostrongyle larval populations on herbage from grazed and ungrazed cattle pastures in south west Scotland. AB - In the course of studies on the control of bovine parasitic gastroenteritis in south west Scotland using a morantel sustained release bolus the populations of trichostrongyle infective larvae on herbage were monitored over a two-year period. From the results of the herbage analysis and the worm burdens in parasite naive tracer calves introduced at the end of 18 months, it was clear that considerable numbers of infective larvae of Ostertagia ostertagi and Cooperia oncophora survived for at least 18 months on pastures not grazed at all. The results suggest that in south west Scotland after one, or even two, seasons with no further contamination of grazing, permanent cattle pastures cannot be assumed to be helminthologically 'safe' and that this should be taken into consideration when determining prophylactic strategies. PMID- 4035087 TI - Blood eosinophilia in adult bantams naturally infected with Trichostrongylus tenuis. AB - Blood eosinophilia was seen in 36 per cent of 115 adult bantams naturally infested with Trichostrongylus tenuis; the maximum individual count was 56 per cent eosinophils. There were no measurable levels of IgE in the plasma samples and no foci of eosinophils were found in the tissues. PMID- 4035088 TI - Viability and pattern of emergence of Dictyocaulus viviparus larvae in sporangia of the fungus Pilobolus kleinii. AB - Recoveries of third stage Dicytocaulus viviparus larvae (L3) from Pilobolus species sporangia ranged from 23 per cent at 21 days to 3 per cent after 90 days for sporangia attached to polythene discs positioned on pasture. There was a continuous release of L3 for up to 16 days from sporangia which were placed under conditions simulating those occurring on pasture. PMID- 4035089 TI - Propionate loading test for liver function in spontaneously ketotic dairy cows. AB - Propionate utilisation by the liver in spontaneously ketotic dairy cows was investigated by determining blood glucose levels after an intravenous sodium propionate load (2.5 mmol kg-1). In addition, blood ketone body concentrations were measured after propionate loading. Cows were divided into three groups (control, mildly ketotic and severely ketotic) by their blood acetoacetate concentrations. Plasma glucose concentrations increased significantly after sodium propionate injection in all three groups (P less than 0.05). The maximum glucose concentration occurred earlier in the control group than in the ketotic groups. Changes in glucose concentrations following propionate loading of control and ketotic cows differed significantly at 20 minutes and beyond. Differences in the change in glucose concentration between mildly ketotic and severely ketotic cows were not significant. Acetoacetate concentration was significantly decreased at five minutes and beyond after the injection in ketotic cows, whereas beta hydroxybutyrate concentration decreased more slowly. A decrease in beta hydroxybutyrate concentration was significant at 40 minutes and beyond in the severely ketotic group and at 10 minutes and beyond in the mildly ketotic group after loading. PMID- 4035090 TI - Experimental 3-nitro-4-hydroxyphenylarsonic acid toxicosis in pigs. AB - Five times the recommended dose of 3-nitro-4-hydroxyphenylarsonic acid (187.5 mg kg-1) induces a pathognomonic clinical syndrome in pigs. The main clinical features are not continually present but are inducible only by exercise. From day 11 on the experimental diet a nervous syndrome was inducible. This manifested as muscle tremors and clonic convulsive episodes. Paraparesis developed by day 22 and paraplegia by day 33. Liver arsenic levels plateaued at 5.4 +/- 1.3 mg kg-1. The experiment confirms field observations that 3-nitro produces a characteristic toxicological syndrome, which is distinct from that of arsanilic acid. It also confirms that 3-nitro has a higher absolute toxicity than arsanilic acid in pigs as well as a lower margin of safety. PMID- 4035091 TI - Gastrointestinal flora in iron-deficient piglets. AB - The pH and microflora of the contents of the stomach and small intestine were studied in iron-treated and iron-deficient piglets. Compared with their iron treated littermates, the gut contents at several sites in iron-deficient animals had a higher pH and contained greater numbers of coliforms, lactobacilli, total aerobes and total anaerobes. The possible relationship of these findings to previous findings in such animals and to their high incidence of diarrhoea is discussed. PMID- 4035093 TI - Hypersensitivity to dietary components in young farm animals: immunisation of calves for IgE antibody responses. AB - An immunisation schedule is described that reproducibly induces long latent period skin sensitising antibody (immunoglobulin) in calves by a combined oral/parenteral route. This response is only directed towards the protein component of the antigen and is boosted upon challenge injection. PMID- 4035092 TI - Immunophysiological activity of supramammary lymph nodes of the ewe during the very early phase of staphylococcal mastitis. AB - Efferent mammary lymph was collected from lactating ewes which were unimmunised (controls) or immunised during pregnancy with two doses of an attenuated live Staphylococcus aureus vaccine either in the hindlimb ("directly primed' supramammary nodes) or in the brisket ("indirectly primed' supramammary nodes). Mammary lymph was also collected from unimmunised animals in which the supramammary nodes had been extirpated several months before. Ewes in which the supramammary nodes had been directly primed by staphylococcal vaccination before challenge had a significantly greater output of IgM- and IgG2-containing cells in lymph and higher concentrations of IgG1 and IgG2 antibody against S aureus surface antigens than did other groups. Lymphadenectomised ewes had fewer leucocytes in mammary lymph but a much higher proportion of neutrophils than other ewes, indicating that afferent mammary lymph has an unusually high number of neutrophils and most of these cells are filtered out in the supramammary lymph nodes under normal circumstances. The results indicated that most of the leucocytes in efferent lymph were derived from the supramammary nodes. After induction of experimental staphylococcal mastitis there was a rapid drop in leucocyte output in lymph within one to four hours after infection; the data indicated that events within the supramammary nodes were responsible for this phenomenon. The output of immunoglobulin-containing cells was reduced during this phase. No significant increases in output of lymphoblasts, immunoglobulin containing cells or specific antibody occurred during the six hours immediately following infection. PMID- 4035094 TI - Formation of calcium complexes by borogluconate in vitro and during calcium borogluconate infusion in sheep. AB - The effect of borogluconate on plasma calcium fractions was studied in vitro and in vivo in sheep. In vitro calcium chloride was more effective in raising ionised plasma calcium than calcium borogluconate. Sodium borate or gluconate added to blood caused only small decreases in blood ionised calcium. However, together, a synergistic reduction in ionised calcium was observed. Following calcium borogluconate infusions into sheep, total plasma calcium rose primarily because of an increase in the unionised ultrafiltrable fraction. Other changes observed following the infusion were hypercalciuria, decreased glomerular filtration rate and acidosis. Sodium borogluconate administered subcutaneously lowered total plasma calcium. This probably resulted from enhanced calcium excretion. It is suggested that since the anionic component of calcium solutions alters the availability and retention of calcium, it is likely to affect clinical efficacy significantly. PMID- 4035095 TI - Safety and efficacy of clavulanate-potentiated amoxycillin in pigeons (Columba livia). AB - Pigeons treated orally with 125 mg clavulanate-potentiated amoxycillin for seven days showed no adverse reactions. The drug had a marked depressive effect on the faecal flora but this had returned to normal 10 days after cessation of treatment. When administered to pigeons with an experimental Staphylococcus aureus infection of the feet no clinical response was apparent and there was no evidence of a diminution in the inflammatory process. PMID- 4035097 TI - Spirochaetes in the equine caecum. AB - Two morphological types of spirochaete were found in the horse caecum measuring 4 to 6 micron by 0.3 to 0.4 micron and 6 to 8 micron by 0.1 to 0.2 micron. Attempts were made to culture the organisms but none survived subculture beyond the primary isolate. Electron microscopy revealed that many of the organisms were infected by bacteriophages. PMID- 4035096 TI - Trichostrongylus colubriformis: in vitro culture of parasitic stages and their use for the evaluation of anthelmintics. AB - Approximately 50 per cent of fourth stage larvae of Trichostrongylus colubriformis taken from the gerbil, Meriones unguiculatus, on day 8 after infection, moulted to the young adult stage when cultured in a complex medium over a seven day period in vitro. Larvae at the late fourth stage of development were highly susceptible to certain benzimidazole, prebenzimidazole, imidazothiazole, pyrimidine, quaternary ammonium, organophosphorus and macrocyclic lactone anthelmintics when any of these were included at very low concentrations in the culture medium. However, few anthelmintics lacking activity against T colubriformis in vivo affected these larvae. An assay employing these larvae in vitro should offer a means for assessing the intrinsic activity of new compounds against T colubriformis in the absence of any complicating host pharmacokinetic factors, and could also be adapted for use as a high capacity preliminary screen. Thus it should now be possible to employ a target parasite at the earliest stages of a lead discovery programme obviating the need to use less relevant free-living nematodes or ones that are natural parasites of rodents. PMID- 4035098 TI - Comparison of two techniques used for the recovery of nematode infective larvae from pasture. AB - The recovery of gastrointestinal nematode infective larvae from herbage collected manually was compared with the recovery from herbage ingested by sheep with oesophageal fistulae, on five occasions during the grazing season. At least three times more larvae were recovered from the oesophageal fistulates than by manual collection. There was no significant variation between the numbers of larvae collected at 09.00, 12.00 and 15.00, nor was there any difference in the distribution of genera recovered by the two methods. The worm burdens of tracer lambs and the larval counts from the fistulated sheep were used to estimate the rate of larval establishment. PMID- 4035099 TI - [Muscle training of the patients during mechanical ventilation]. PMID- 4035100 TI - [Mucociliary clearance mechanisms studied by radioisotopic methods--a quantitative analysis]. PMID- 4035101 TI - [The relationship between the extent of coronary artery disease and correlative risk factors in young men]. PMID- 4035102 TI - [Electrophysiological assessment of patients with recurrent ventricular tachycardia after myocardial infarction]. PMID- 4035103 TI - [Early non-invasive diagnosis of ventricular septal rupture following acute myocardial infarction: role of two-dimensional and pulsed Doppler echocardiography]. PMID- 4035104 TI - [Surgical anatomy of resected rheumatic mitral valves]. PMID- 4035105 TI - [Postextrasystolic potentiation after total or partial coronary occlusion in dogs]. PMID- 4035106 TI - The matching of ventilation and perfusion in the lung of the Tegu lizard, Tupinambis nigropunctatus. AB - Ventilation-perfusion (VA/Q) distribution was evaluated in the Tegu lizard, Tupinambis nigropunctatus, using the multiple inert gas elimination technique (MIGET) in order to define the limitations to gas exchange in the large chambered unicameral lung. The lizards (0.52-1.1 kg) were anesthetized with halothane and ventilated. Body temperature was maintained at 35 degrees C. Arterial and sinus venosus PO2 averaged 79.4 +/- 5.9 and 47.3 +/- 6.4 torr while breathing air and 232.1 +/- 31 and 64.8 +/- 11.5 torr while breathing oxygen. VA/Q distributions were broad and right-to-left shunt averaged 21% while breathing air and 27% while breathing oxygen. Gas exchange was significantly impaired due to the presence of both shunt and VA/Q heterogeneity. The walls of the lung enclose a large axial air chamber. Microscopic examination revealed approximately three generations of septa which subdivided the wall into tubular-shaped gas-exchange chambers. Wall thickness averages 2.8 mm at the anterior end of the lung, 2.1 mm in the middle portion of the lung and 1.4 mm at the posterior end. The thickness of the blood air barrier (epithelial-basal lamina-endothelial cell layer) ranged from 0.35 to 0.90 micron. Although this barrier is slightly thicker than in the mammalian lung (0.1-0.5 micron), it is unlikely to be a source of diffusion limitation in gas exchange at rest. PMID- 4035107 TI - Gas exchange in tidally ventilated and non-steadily perfused lung model. AB - We studied the effect of cyclic lung perfusion - fast cycle in synchrony with heart beats and slow cycle in synchrony with ventilation - on gas exchange in a lung model. There was almost no effect in the fast cycle. In a homogeneous single lung unit, arterial PO2 increased, and the (A - a)DO2 decreased (by approximately 0.5 Torr), as the amplitude of the slow cyclic lung perfusion (TIP) increased. The calculated (A - a)DO2 and (a - A)DCO2 were negative. Maximal PaO2 was found when peak lung perfusion was delayed with respect to ventilation by 0.2 of a cycle. In a non-homogeneous nine-unit lung, cyclic lung perfusion caused an increase in PaO2 and a decrease in (A - a)DO2 by 2 Torr as compared to steady perfusion. No apparent negative (A - a)DO2 was found, but apparent negative (a - A)DCO2 was calculated at no pulmonary shunt and also with 5% shunt. The correlation of cyclic lung perfusion to the reduced (A - a)DO2 in dense-gas breathing - where large swings of pleural pressure are expected - and its effect on the diffusion capacity of the lung are discussed. Non-steady perfusion of the lung as caused by ventilatory movements expanded our understanding of gas exchange and shed some light on a few controversial experimental findings, such as the negative (a - A)DCO2, the decreased (A - a)DO2 while breathing dense gas, and the effects of gas density on diffusion capacity of the lung. PMID- 4035108 TI - Reflex partitioning of inputs from stretch receptors of bronchi and thoracic trachea. AB - A selective block of slowly adapting stretch receptors in anesthetized rabbits was induced by exposing to SO2 all thoracic airways (T) or the carina and bronchi alone (B). Increment of inspiratory time (TI) relative to control was 61% greater under B than T. The reverse would have happened if input responsible for Breuer Hering inflation reflex originated from both bronchi and trachea. Hence, bronchial input activates inspiratory off-switch, while tracheal input delays its activation. During single inspiratory efforts with airways closed at end expiration diaphragm activity (Adi) decreased and TI0 increased relative to control equally under B and T. Hence, the input facilitating central inspiratory activity at end expiratory volume does not stem from trachea. At end of inspiratory ramp Adi stopped within 43 msec at control and 57 msec under B and T. Hence, bronchial input speeds up off-switching of inspiration. Postinspiratory Adi was greater under B than T, and nearly nil at control. Hence, bronchial input inhibits postinspiratory Adi, while tracheal input facilitates it. Inspiratory and expiratory flows were more damped under B than T, and under T than at control. PMID- 4035109 TI - Effective resistance of the respiratory system studied by a quick release technique. AB - A human subject with mouthpiece in place makes inspiratory or expiratory effort against a closed shutter which abruptly opens when a predetermined pressure (PO) is developed. Pressure at the mouth (Pao) and flow (V) are continuously recorded. When the shutter opens, Pao changes toward atmospheric - first abruptly and then gradually, while V rapidly rises to a peak value (Vpeak) and then gradually declines. In any series of trials PO is held constant, but resistance external to the subject (Rext) is changed with each trial. In different series PO is varied. In any series of trials at constant PO the relationship between Pao and V was linear. The slope (K) of the straight line fitted to the experimental points was interpreted as being equal in magnitude to the 'effective resistance' (Reff) of the respiratory system. Reff has two components - a true resistance (Rint) and a virtual one (Rfv) related to the force-velocity characteristic of the respiratory muscles. On the assumption that Rint is independent of PO but that Rfv varies linearly with it, Rint and Rfv can be evaluated. PMID- 4035110 TI - Comparison of phrenic motoneuron activity in eupnea and apneusis. AB - Our purpose was to characterize activities of phrenic motoneurons during apneusis. In decerebrate, cerebellectomized, vagotomized, paralyzed and ventilated cats, we recorded activities of phrenic nerve and single phrenic fibers during eupnea and apneusis. Reversible apneusis was obtained by cooling the rostral pons with a fork thermode. Phrenic motoneurons were defined as 'early' or 'late' during eupnea. Early units commenced activity before or during the first 20% of neural inspiration. The onset of discharge of late units extended throughout the rest of inspiration. In apneusis, some late units ceased activity entirely; others commenced activity at the end of the rising phase of phrenic activity or during the apneustic plateau. Early units commenced activities at the same time as in eupnea and generally maintained the same discharge frequency. Hence, the ramp phase of phrenic discharge in apneusis is generated largely by activities of early motoneurons. Our results imply that the level of bulbospinal activity impinging upon the phrenic nucleus is reduced in apneusis. The integration of efferent activity within the phrenic nucleus is discussed. PMID- 4035111 TI - Chemo- and baroreceptor innervation of the aortic trunk of the toad Bufo vulgaris. AB - In the toad Bufo vulgaris, afferent impulses were recorded from the fine branch of the vagus which terminates in the aortic trunk. Spontaneous single unit discharge was random. When the aorta was artificially perfused, units fired in response to flow change, hypoxia and hypoxia-hypercapnia of the perfusion fluid, and administration of NaCN or Ach. A few baroreceptor fibers fired synchronously with the blood pressure fluctuation. In anesthetized toads with other reflexogenic areas denervated, the intravenous administration of NaCN caused an increase in breathing and a slight elevation of blood pressure. When the nerve concerned was cut, these responses were abolished. Electrical stimulation of the nerve's central cut end brought about the same type of response as that to NaCN. Special cells closely resembling the glomus cells in the carotid labyrinth were found in the aortic wall. In amphibia, there is an aortic nerve corresponding to that of mammals, and the aorta is one of receptive areas predominantly contributing to respiratory control. PMID- 4035112 TI - The reliability of respiratory quotient measurements. AB - A graphical analysis is presented which allows the assessment of confidence in the measurement of the respiratory quotient in an open-circuit metabolic chamber as a function of an organism's metabolic rate, the chamber ventilation, the magnitude of the respiratory quotient and the sensitivity of the gas analyzers. PMID- 4035113 TI - Pores in avian eggshells: gas conductance, gas exchange and embryonic growth rate. AB - The number of pores (N) in eggshells of birds were counted in 161 species ranging in egg mass (W) from 0.9 to 500 g. In addition the water vapor conductance of the shell (G) mg X (d X Torr)-1, the water loss in the nest (M) mg X d-1, the incubation duration (I) d, and the shell thickness or pore length (L) micron are listed for each species when available. Allometric equations for all variables are given when regressed on egg mass. When log G is regressed on log N the slope is essentially 1.0 indicating that the G X N-1 for average pores in bird eggshells is 1.5 micrograms H2O X (d X Torr)-1 regardless of egg mass or incubation duration. According to Fick's law of diffusion such pores have a cross sectional area to pore length ratio of 0.67 micron 2 X micron-1. Further analysis show that N, G, M, and the rate of oxygen consumption at the pre-internal pipping stage, are all directly proportional to the absolute mean growth rate of embryos (defined as 0.67 [W/I], g X d-1). Thus, single pores of typical eggshells not only have a similar conductance G X N-1, but also the metabolic rate and rate of water loss are matched to the pore conductance so that O2, CO2 fluxes per pore at the pre-internal pipping stage and water vapor flux per pore are similar among species, namely 68, 49 and 50 microliters X d-1, respectively. The partial pressure differences across the shell at the same stage are 42, 40 and 27 Torr, respectively. Ecological as well as taxonomical variation may alter some of the relationships predicted for the 'typical' egg in order to conserve a typical overall diffusive water loss. PMID- 4035114 TI - The rectilinear pressure-flow relationship in the pulmonary vasculature: zones 2 and 3. AB - To elucidate the significance of the rectilinear pressure-flow relationship of the pulmonary vasculature under zone 2 and 3 conditions, isolated left lower lobes of dog lungs were perfused at different flow rates under the two zone conditions. The lobar arterial pressure (Pa) was measured directly, whereas the pressures in the peripheral end of the arteries (Pa') and veins (Pv') were measured with the arterial and venous occlusion (AVO). We thus obtained three pressure-flow relationships: Pa-Q, Pa'-Q and Pv'-Q. From these relationships the contribution of each of the three segments (defined by the arterial and venous occlusion) to the slope and intercept of the Pa-Q relationship was determined. To a first approximation, in zone 3 the ohmic resistance was mainly in the arterial and venous segments, whereas the Starling resistance, although small, was equal in the three segments. In zone 2 (Palv = 15 mm Hg) the Starling resistance increased markedly in the middle segment. Because zone 3 and 2 conditions can co exist within the lung, a simple three-segment model to represent the pulmonary vasculature was inadequate to explain all the pressure-flow data and therefore was modified to include two parallel channels one of which contains a critical closing pressure (Pc). Such a model implies that two different driving pressures determine the total flow: in vascular channels where Pc greater than Pv (outflow venous pressure) flow is determined by Pa-Pc gradient, and in channels were Pc less than Pv flow would be determined by the Pa-Pv gradient.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4035115 TI - High frequency oscillation of the lungs alone lengthens expiration in dogs. AB - High frequency (15 Hz), low volume (approximately 40 ml) oscillation of the respiratory system lengthens expiration in anesthetized dogs even in the absence of changes in mean expiratory lung volume or blood gases (Banzett et al., 1983). Although vagotomy abolishes this response, we felt it might mask the reflex rather than interrupt the afferent pathway. To ascertain whether pulmonary and airway afferents alone are capable of evoking this reflex, we confined the oscillatory stimulus to the lung by widely opening the chest. The dogs were paralyzed but breathed 'spontaneously' by means of a solenoid valve opened and closed by the phrenic neurogram. End-expiratory lung volume and PCO2 were held constant. All eight dogs that were tested after thoracotomy lengthened expiration during oscillation. Although quantitative comparisons of responses before and after thoracotomy are not entirely reliable, we could see no consistent change in the strength of response with paralysis or with thoracotomy. We conclude that the principal afferent limb of the ventilatory reflex response to oscillation arises in the lungs and intrathoracic airways. PMID- 4035116 TI - Responses of early and late onset phrenic motoneurons to lung inflation. AB - In anesthetized or decerebrate cats that were paralyzed and ventilated with a cycle-triggered pump, we produced changes in activity of the whole phrenic nerve and of individual phrenic motoneurons (fibers or cells in the spinal cord) by withholding lung inflation during the inspiratory (I) phase. The neurons were classified into early- and late-onset types (discharge onset less or greater than 80 msec, respectively, after whole phrenic onset). Both unit and whole phrenic activity exhibited a variety of responses to inflation (excitation, depression, or no effect); but there were no consistent differences between responses of early- and late-onset neurons. The distribution of responses was quite different from that of dorsal respiratory group (DRG) I neurons (Cohen and Feldman, 1984); in particular there was no group of phrenic neurons corresponding to the late onset I-beta neurons (I neurons excited by inflation). We conclude that the inputs to late-onset phrenic neurons are not predominantly or exclusively from late-onset DRG neurons. PMID- 4035117 TI - [Hormone determination and biopsy of the testicle in the sterile male]. PMID- 4035118 TI - [Testicular response to human chorionic gonadotropin in infertile patients according to the testicular histologic pattern]. PMID- 4035119 TI - [Generalized lupus erythematosus. Hormonal studies in patients with secondary amenorrhea]. PMID- 4035120 TI - [Treatment of acute demyelinating inflammatory polyradiculoneuritis with megadoses of methylprednisolone. Prospective study]. PMID- 4035122 TI - [What patients with cerebrovascular embolism of cardiac origin should be anticoagulated?]. PMID- 4035121 TI - [Parasitosis in the bile ducts: Fasciola hepatica]. PMID- 4035123 TI - [Non-steroidal anti-inflammatory agents. A practical review]. PMID- 4035124 TI - [Preparation of 99mTc radiopharmaceuticals; quality control. Detection of pyrogens by the Limulus amebocyte lysate test]. PMID- 4035125 TI - [Abnormalities of the esophageal hiatus in Sugiura's operation]. PMID- 4035126 TI - [Morbidity and mortality of central intravenous catheters. Prospective study at the Instituto Nacional de la Nutricion Salvador Zubiran]. PMID- 4035127 TI - [Aspergillus infection at the Instituto Nacional de la Nutricion Salvador Zubiran. Study of 17 autopsy cases]. PMID- 4035128 TI - [What can be expected from computers in the ORL practitioner's office?]. PMID- 4035129 TI - [Computerized and functional studies in ORL]. PMID- 4035130 TI - [Computer data processing of the signal]. PMID- 4035131 TI - [From automatic data processing to telematics]. PMID- 4035132 TI - [Cervicofacial hydatid cyst. Apropos of 9 cases]. PMID- 4035133 TI - [Kimmerle's anomaly and vertebrobasilar insufficiency]. PMID- 4035135 TI - Anatomical characteristics of the sinus epitympani anterior. PMID- 4035134 TI - [Innervation of the sternocleidomastoid muscle]. PMID- 4035136 TI - Vertigo in vertebral-basilar insufficiency. PMID- 4035137 TI - [Evaluation of the use of the combination sulfamethoxazole-trimethoprim ornidazole in the prevention of infections in major ORL surgery and otoneurosurgery (on 100 cases)]. PMID- 4035138 TI - [Standardization of Quick's time]. PMID- 4035139 TI - [The role of radiotherapy in the treatment of lung cancer]. PMID- 4035140 TI - [Sleep in school-age children]. PMID- 4035141 TI - [Thyroid pathology iatrogenically induced by iodinated products]. PMID- 4035142 TI - [Iatrogenic coagulopathies]. PMID- 4035143 TI - [Drug-induced impotence]. PMID- 4035144 TI - [The pitfalls of drop-attacks]. PMID- 4035145 TI - [Chronobiology and chronopharmacology: an urgent demonstration. General introduction to chronobiology]. PMID- 4035147 TI - [Chronopharmacology and chronotherapeutics]. PMID- 4035146 TI - [Chronobiology in endocrinology]. PMID- 4035148 TI - [Anterior transiliac bone biopsy and quantitative histomorphology of bone. Value in osteoarticular pathology]. PMID- 4035149 TI - Differential sensitivity to airpuffs on human hairy and glabrous skin. AB - To compare the relative sensitivities of glabrous and hairy skin, we measured reaction times (RTs) and detectability (d') of airpuffs delivered to the hairy dorsum and glabrous thenar eminence of the hand of six human subjects. In contrast to previous studies with mechanical contact stimuli, airpuffs applied to hairy skin were detected with equal or greater fidelity than airpuffs tested on glabrous skin. Mean RTs to three simultaneously applied airpuffs were significantly shorter (p less than .005) on hairy skin in five of six subjects, and in 74% of paired sessions; no significant difference in mean RTs was observed in 16% of the sessions. The superiority of hairy skin was less evident, however, when single airpuffs were tested, as significantly shorter responses were observed on only 45% of the paired sessions, and nearly identical responses on 38% of the sessions. Detectability of airpuffs (d'), which is independent of the value of RTs, was identical on hairy and glabrous skin at high airpuff intensities (1,600 dyn), and superior (n = 4) or equal (n = 2) on hairy skin with low airpuff intensities (800 dyn). Spatial summation was more pronounced on hairy than on glabrous skin. Three simultaneously presented airpuffs produced significantly shorter RTs than one airpuff in 85% of the paired sessions on hairy skin, but on only half of the sessions on glabrous skin. The spatial distribution of stimulus force was less important on hairy skin, as three low-intensity airpuffs produced the same or shorter RTs than one high-intensity airpuff. By contrast, on glabrous skin, detectability was significantly better when force was concentrated at a single point (1 X 1,600 dyn) than when diffused over a wide skin area (3 X 800 dyn). The enhanced sensitivity of hairy skin to airpuffs appears partially attributable to hair motion in the airstream. After hair removal by chemical depilation, detectability of airpuffs was reduced on hairy skin to a level equal to or below that on glabrous skin. Spatial summation on the depilated skin corresponded to that observed on the intact hairy skin, indicating that depilation did not abolish intensity discrimination, but rather lowered the overall sensitivity of hairy skin. These results show that hair follicle units form a very sensitive detection mechanism on hairy skin of the human hand, similar to that provided by Meissner's and Pacinian afferents in glabrous skin. These findings with airpuffs provide the first example of a tactile stimulus that is less effective for mechanoreceptors in glabrous skin than in hairy skin.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 4035150 TI - The primate as a model for the human temperature-sensing system: 1. Adapting temperature and intensity of thermal stimuli. AB - The thermal sensitivity of three humans and two rhesus monkeys was measured behaviorally, using the "yes-no" paradigm of the Theory of Signal Detection. The aim was to evaluate the monkey's thermal-sensing system as a model for that of humans. Three of the principal variables of human thermal sensations--rate of the temperature change, area of stimulation, and site of stimulation--were held constant. The other three variables--adapting skin temperature (AT), intensity, and direction of the temperature change--were varied systematically. Systematic differences between species were not evident for warming or cooling stimuli. Isodetectability curves (d'e = 1) for small cooling stimuli plotted as a function of the AT were isomorphic, and the points for the human and monkey subjects were frequently superimposed. Isodetectability curves for warming stimuli, on the other hand, had similar shapes for ATs between 33 degrees and 40 degrees C, but the points for the different subjects were not superimposed. At ATs below 30 degrees C, one of the two humans in the warming series and the two monkeys continued to show similarly shaped curves, but the other human was markedly different. Qualitative descriptions of the thermal sensations obtained during threshold measurements of human subjects, reported previously, suggest that this unusual subject probably adopted a criterion qualitatively different from that used by the other subjects. The data presented here and in combination with previously published work from this laboratory (Kenshalo, 1970) suggest that thermal stimuli produce similar sensations in rhesus monkeys and humans, and that the neural systems responsible for coding AT and temperature change in the two species are fundamentally similar. PMID- 4035151 TI - The primate as a model for the human temperature-sensing system: 2. Area of skin receiving thermal stimulation (spatial summation). AB - The thermal sensitivities of three humans and one monkey were measured using the "yes-no" paradigm based on the Theory of Signal Detection. The aim was to evaluate the monkey's thermal-sensing system as a model for that of humans. Three of the principal variables of human thermal sensations--the temperature to which the skin was adapted, the rate of temperature change, and the site of application of the thermal stimuli--were held constant. The other three variables--area of stimulation, intensity, and direction of the temperature change--were varied systematically. All four subjects displayed spatial summation for both warming and cooling. Isodetectability curves (d'e = 1) to small temperature changes, both for humans and for the monkey, could reasonably be fitted by the function I = kappa A-b, where I is stimulus intensity, A is the area of stimulation, and b is the rate at which spatial summation occurred. The rate of summation, b, to warming stimuli for the humans ranged from 0.60 to 1.14, while that for the monkey was 0.14. The rate of summation to cooling stimuli for the humans ranged from 0.50 to 0.87, while that for the monkey was 0.43. The main species difference was that summation on the monkey palm all but ceased for both warming and cooling stimuli applied to areas larger than 4 cm2. Data from the human subjects did not demonstrate an upper limit of spatial summation. However, there was an indication that the human subjects would show a ceiling for spatial summation near the largest area tested in this study. Thus, when considering the spatial extent of a thermal stimulus and its influence upon thermal sensations, it may be more appropriate to compare areas relative to body size, rather than absolute values. PMID- 4035152 TI - Response of ventrobasal thalamic neurons activated by dorsal and dorsolateral funiculi: an intracellular study. AB - Intracellular responses to stimulation of the dorsal column (DC) and dorsolateral funiculus (DLF) were recorded in cells of the thalamic ventrobasal complex (VB) in anesthetized cats, with the dorsal funiculi either intact or isolated. The responsiveness of VB neurons was tested using graded stimulation, paired-shock, and interaction techniques. Of the 60 VB neurons thoroughly studied, 50 responded to stimulation of the DC with excitatory postsynaptic potentials (EPSPs) followed by inhibitory postsynaptic potentials (IPSPs); half of these 50 neurons responded to stimulation of the DLF with the same pattern, whereas no IPSPs could be elicited in the remaining neurons. The majority of EPSPs could be fractionated into unitary components during graded electrical stimulation. The number of such components observed was greater after DLF than after DC stimulation. In most neurons, the DLF-evoked EPSPs were smaller in amplitude than the DC-evoked EPSPs. Paired-shock stimulation facilitated the DLF excitatory responses. The amplitude of IPSPs induced by DLF stimulation was significantly smaller than that evoked by DC stimulation, and DC stimulation reduced the excitatory response to subsequent DLF stimulation. The data support the known dominance of the DC pathway in the cat. PMID- 4035153 TI - [Indications and contraindications for anesthesia in ambulatory surgery]. PMID- 4035154 TI - [Orthopedics and ambulatory surgery]. PMID- 4035156 TI - [Ambulatory proctological surgery]. PMID- 4035155 TI - [Ambulatory surgery in hand surgery]. PMID- 4035157 TI - [Ambulatory surgery in urology]. PMID- 4035158 TI - [Ambulatory surgery in otorhinolaryngology]. PMID- 4035159 TI - [Ambulatory maxillofacial surgery]. PMID- 4035160 TI - [Dry chemistry in medical practice. Possibilities and problems]. PMID- 4035161 TI - [Collective psychoses]. PMID- 4035162 TI - [How do various occupational groups perceive epileptics?]. PMID- 4035163 TI - [Tenoxicam in the treatment of arthroses]. PMID- 4035164 TI - [Productive cough]. PMID- 4035165 TI - [Lesions of the upper ankle joint]. PMID- 4035166 TI - [Anatomy of the ankle joint]. PMID- 4035167 TI - [Circulation disorders in the ankle region]. PMID- 4035168 TI - [PNF--proprioceptive neuromuscular facilitation]. PMID- 4035169 TI - [Anatomic correlates of cerebral dominance]. PMID- 4035170 TI - [The role of the upper limb in the evolution of the species and in the human stakes]. PMID- 4035171 TI - [The blood pressure profile. A new method of confirmed value]. PMID- 4035172 TI - [Psychiatric problems in aeronautic medicine]. PMID- 4035173 TI - [Ethical problems in neonatology]. PMID- 4035174 TI - [Atypical manifestations of aneurysm of the abdominal aorta]. PMID- 4035175 TI - [The place of the dietary questionnaire in the patient's medical history]. PMID- 4035176 TI - The omentum in malignant diseases. AB - The technique and applications of omentoplasty are reviewed from the point of view of the surgical oncologist, with particular emphasis on the use of the omentum in gastrointestinal anastomoses, covering peritoneal defects or radical intra-abdominal operations for neoplastic disease, urological complications, breast cancer, abdominal and chest wall resections, the prevention of arterial graft erosions, and the treatment of lymphoedema and chemotherapeutic burns. Complications are discussed as well as future prospects. PMID- 4035178 TI - Radical hysterectomy for cancer of the uterine cervix. AB - A recent modification of radical hysterectomy for cancer of the uterine cervix is described in detail. This modification of the Okabayashi operation has shown improved reliability and safety. Because of the extensive resection of supporting ligaments and loose connective tissue, bleeding may be induced and a wide operation field is necessary to prevent injury to the pelvic viscera. PMID- 4035177 TI - Surgery of esophageal carcinoma. AB - The experience of surgical treatment in 1,874 patients with carcinoma of the esophagus seen at the Cancer Institute and Hospital of the Chinese Academy of Medical Sciences, Beijing, People's Republic of China, between 1958 and 1982, is reported. Despite the prevalence of this malignancy in this part of China, only 3% of the patients in this series had stage I disease, while 80% of the patients had either stage III or stage IV disease with extraesophageal tumor invasion and regional or distant metastases. Of the entire series there was an overall resectability rate of 83.9%, being 77.6% between 1958 and 1969 and 89.0% between 1970 and 1982. Among the 1,572 resections of the entire series, there were 66 deaths within 30 days of operation, for a resection mortality rate of 4.2%, being 4.9% between 1958 and 1969 and 3.7% between 1970 and 1982. Anastomotic leakage occurred in 67 cases of the 1,572 resections, for an incidence of 4.3%. Of the 67 cases with anastomotic leaks, 38 recovered after intensive treatment; the remaining 29 died eventually of the complication, giving a death rate of 43.3%. Pathologic studies of the 1,572 specimens showed lymph node metastasis in 46.1% of the cases. It is obvious that practically all the unresectable cases showed more extensive lymph node involvement at operation, although fixation of the tumor with severe invasion to the surrounding organs usually constituted the chief cause of unresectability. The postresection long-term survivals as calculated by the number of resections at 5, 10, and 15 years were 30.2% (390/1293), 22.4% (196/876), and 18.9% (112/594), respectively. Over one-third, or 36.8%, of the 1,874 patients in the present series were treated with a combination therapy of preoperative irradiation and surgery. The results in the group of 408 selective patients and those in the group of 83 randomized patients with midthoracic esophageal carcinomas were gratifying. In the latter group there was a resectability rate of 95.2%, a resection mortality rate of 3.8%, an incidence of intrathoracic anastomotic leakage of 0%, and a 5-year survival rate of 45.5%, as compared to 89.6%, 4.3%, 1.7%, and 25%, respectively, in the control group treated by surgery alone. From these findings it is concluded that preoperative irradiation as an adjunct can promote both the immediate and long term results of surgery for carcinoma of the esophagus. Recent advances in the surgical treatment of carcinoma of the esophagus may change the pessimistic philosophy for this malignancy.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 4035179 TI - Summary report of worldwide antibiotic resistance: international task forces on antibiotic use. PMID- 4035180 TI - Retrospective commentary on the bacterial endocarditis study. PMID- 4035181 TI - [Glucosephosphate dehydrogenase deficiency and hemotherapy in Brazil]. PMID- 4035182 TI - [Myectomy of the arytenoid in bilateral paralysis in adduction of the vocal cords: microsurgical technic by endoscopic approach]. PMID- 4035183 TI - [Evaluation of 100 radiographs in a medical department of a plant in Greater Sao Paulo]. PMID- 4035184 TI - [Actinic pneumonitis: not to be confused with tuberculosis]. PMID- 4035185 TI - [Dicephalus dipus dibrachius]. PMID- 4035187 TI - [Pruritus vulvae]. AB - Vulvogenital pruritus is due to infectious, dystrophic or dermatological causes. Diagnoses of "senile" or "psychogenic" pruritus do not obviate the need for regular surveillance. Treatment is easy if the cause is duly recognised. It is more difficult in essential forms and the authors describe the principles and methods of symptomatic treatment. PMID- 4035186 TI - [Thoracic trauma: a rare etiology of total atrioventricular block]. PMID- 4035188 TI - [Functional hyperprolactinemia]. AB - Treatment remains the same whether there is true idiopathic hyperprolactinemia or microadenomas too small to be detectable by methods of investigation. Bromocriptine has an antitumoral effect and treatment can often be stopped after the disappearance of a microadenoma or even of a larger adenoma. "Cure" of idiopathic hyperprolactinemia is rarer. PMID- 4035190 TI - [In vitro fertilization or surgery in the treatment of tubal sterility]. AB - Although it is very difficult to compare the results of the two methods, it would seem that those of tubal surgery remain more or less stationary whilst those of fertilisation in vitro improve and the technique becomes more simple. PMID- 4035189 TI - [Dynamic tests for monitoring fetal cardiac rhythm]. AB - The oxytocic test was compared in 354 cases of "high risk" pregnancy with the simple recording of fetal heart rate. When the tracing of the simple recording was normal, the oxytocic test revealed a frankly pathological tracing in only 2.5 p. cent of cases. By contrast, if there were abnormal signs in the simple record, the oxytocic test was pathological in only 18.8 p. cent of cases. The test has only a relative value, as indicated by analyses of modes of labor and of the state of the child at birth. PMID- 4035191 TI - [Treatment of dysplasias and cancers of the cervix. In defense of and illustration of the conization procedure using a cold scalpel under local anesthesia with hospitalization for a day]. AB - A series of 143 cone biopsies performed for carcinoma in situ between October 1st, 1981 and July 31st, 1984 is described. Complications were rare: reoperation in 1.5 per cent of cases. "Oncological" results were good. There were few failures: 3.5 per cent of cases. Examination of the operative specimen revealed occult invasive carcinomas: 12.3 per cent of cases. It was also used to identify patients with a "high risk of recurrence", those in whom the resection had not passed through "healthy" tissue: 28.0 per cent of cases. Performed under local anaesthetic using a cold scalpel and with day hospitalisation, the operation is easy and inexpensive (1 309.71 francs). PMID- 4035192 TI - [Hormonal dependence and hormonal therapy of cancers of the endometrium and breast]. AB - After briefly reviewing in outline the role and biochemistry of hormonal receptors, the author draws a number of logical conclusions concerning hormone treatment of carcinomas of the breast and of the endometrium. PMID- 4035193 TI - [Repeated spontaneous abortion]. AB - This review of the causes of recurrent spontaneous abortion is combined with a statistical evaluation of the frequency of abortion and of the probability of abortion according to the way in which previous pregnancies have ended. PMID- 4035194 TI - [Fate of infants weighting less than 1,500 grams]. AB - Between 1981 and 1983, 251 premature infants with a birth weight of less than 1 500 grams were admitted to the Neonatal Pathology Unit of the E. Herriot hospital (malformations excluded). Forty two (17%) died during the neonatal period. These premature births resulted essentially from pathological pregnancies: multiple pregnancies (1/5 cases), renal pathology (1/3 cases), placental abnormalities (10%) and fetoplacental infections (10%). In half of all cases delivery was by cesarian section, indicated in 85% of cases because of acute or chronic fetal distress. These premature infants suffered from respiratory (including 40% hyaline membrane disease), neurological (abnormal cerebral echotomography with dilatation or intracranial haemorrhage in 35% of cases), infectious (6%) and digestive (6% necrosing enterocolitis) pathology. Of the 208 surviving children, 12 (i.e. 6% of the survivors) had major sequelae (with follow-up of one year or more). PMID- 4035195 TI - [Management of molar pregnancy. Diagnosis of choriocarcinomas and invasive moles]. AB - The management of a molar pregnancy is envisaged on the basis of experience involving the evacuation and surveillance of a mole in 109 cases. A pathological and cytogenetic distinction is drawn between perivillous hyperplasia (102 cases) and embryonic mole or triploid syndrome (7 cases). The diagnosis of choriocarcinoma (20 cases) and of invasive moles (28 cases) is envisaged on the basis of a series including 59 cases of abnormal post-molar or post-partum course. The diagnosis may be approached by pelvic arteriography and the Ishizuka severity scale. A diagnosis is important in the selection of appropriate treatment: clinical surveillance for simple delayed involution, single drug chemotherapy for invasive moles and polychemotherapy after thorough radiological and echotomographic assessment for choriocarcinoma. PMID- 4035196 TI - [Round table: Adjuvant treatment in stage I and II cancers of the breast]. PMID- 4035197 TI - [Larger amounts of copper correspond to greater contraceptive effectiveness. Experiments with the ML Cu 375, the IUD with the highest copper content]. PMID- 4035198 TI - [Comparison of two skin antiseptics in blood transfusion. Comparison with the results of the bacteriologic control of labile blood products]. AB - The comparison of two skin antiseptics (70 degrees alcohol and 0,5% alcoholic chlorhexidine solution) was carried out by the method of in vivo impressions. The study used 45 healthy volonteers from whom a bacteriological sample was taken from both bends of the elbow, without use of an antiseptic, and after the application of one according to usual sample taking methods. The subjects were divided into two sets according to the antiseptic being tested. The results of the cultures after 24 and 48 hours are expressed in the number of germs per cm2, which thus permits us to calculate a reduction in percentage or log 10 form, and to appreciate the efficiency of the antiseptic studied. Routine bacteriological inspection of labile blood products was carried out on products picked at random every week during 18 months of exclusive use of 70 degrees alcohol by the sample taking services. The results show a comparable in vivo effectiveness of the two antiseptics on the superficial aerobic flora of the bend of the elbow, and the ease of use of 70 degrees alcohol has led to its choice. This choice is confronted with the results of the inspection of blood products: out of 1 293 inspections, only one slight contamination (cocci gram+) was found on a unit of whole blood. These data as a whole can be compared with the work of various authors. PMID- 4035200 TI - [Limulus test using a chromogenic method: application to the control of pyrogens in blood derivatives]. AB - We report here the application of the LAL Test to a chromogenic substrate to detect endotoxins in Human Blood Products. In order to reduce the cost, we used a microplate procedure with the Multiskan Reader. Quantitative results in the range of 0,01 to 0,1 ng/ml allowed for a good correlation with the Rabbit Pyrogen test. For 20% albumins and 4% albumins, the mean endotoxins levels of non pyrogenic lots were 0,38 +/- 0,18 and 0,09 +/- 0,03 ng/ml. All the lots which passed the Rabbit Pyrogen test had endotoxins levels lower than 1 ng/ml and 0,2 ng/ml, respectively. We can use this test for other plasma derivatives; Gammaglobulines and PPSB are easily tested. Dried Concentrated Antihemophilic Factor and Dried plasma contain citrate which inhibits the reaction. Dilution and Addition of Calcium Chloride overcome this inhibition. For dried plasma, we should destroy plasma inhibitors by heating at 75 degrees C. This sensitive and reproductible in vitro assay improves the control of pyrogenecity in Human Blood Products. PMID- 4035199 TI - [Prevalence of hepatitis B viral markers in Vietnamese blood donors]. AB - Serum samples were assayed using radioimmunoassay in 573 Vietnamese blood donors living in Hanoi (North Viet Nam). 66 (11.5%) subjects were HBsAg-positive. Of these 66 HBsAg carriers, 17 (25,8%) were positive for hepatitis B e antigen (HBeAg) and 43 (65.1%) for antibody to HBeAg (anti-HBe). 22 (3.8%) subjects were positive for antibody to hepatitis B core antigen (anti-HBc) alone. 402 (70.2%) subjects were positive for antibody to HBsAg (anti-HBs). This anti-HBs percentage increased with age. Only 83 (14.5%) subjects were negative for all hepatitis B viral (HBV) markers. This no HBV markers percentage decreased with age. The chi 2 test showed a non significant difference for frequencies of HBsAg, anti-HBc alone, anti-HBs but a significant one for frequencies of no HBV markers in men and women. PMID- 4035201 TI - [Automated maintenance of a central file of blood donors]. AB - Data processing of medical information gathered by the physician working in the mobile unit, has been optimized and automatized. Thanks to the simultaneous use of an optical mark reader and a lightpen it is possible to achieve a quick data entry without a manual keyboard as soon as the mobile blood units bring back the samples. The donnors' medical cards which accompany each blood sample are transmitted from the mobile unit to the laboratory for better test accuracy. This simple system, operating since October 1984, has proven its reliability and efficiency. PMID- 4035202 TI - Cell mediated immune response in canine antirabies vaccination. PMID- 4035203 TI - [Epidemiological study among Indian groups of Rondonia. I--Pyoderma and asymptomatic carriers of Staphylococcus sp. in the mouth and nose among Surui and Karitiana Indians]. PMID- 4035204 TI - [Natural infection of Ptychophallus tristani (Crustacea: Decapoda) by metacercariae of Paragonimus mexicanus (Trematoda) in Tabarcia de Mora, Costa Rica]. PMID- 4035205 TI - [An attempt to eradicate hymenolepiasis in a semi-closed community using praziquantel]. PMID- 4035206 TI - [Therapeutic efficacy of praziquantel and morphological changes in Hymenolepis nana eggs after its administration in 2 dosage schedules]. PMID- 4035208 TI - [Susceptibility of Biomphalaria tenagophila hybrids to the LE (BH) strain of Schistosoma mansoni]. PMID- 4035207 TI - [Fatal pulmonary infection caused by Lagochilascaris sp., probably Lagochilascaris minor Leiper, 1909]. PMID- 4035209 TI - [Blood viscosity: an original method for the study of low values of the shear rate]. AB - A method for studying blood viscosity at low shear rates (from 4 x 10(-2) to 7 x 10(1) sec-1), i.e. in the shear range in which higher is the influence of shear rate on viscosity, was developed. Blood viscosity is expressed by the two regression coefficients of a power regression, according to the function: eta = a . Db where eta is viscosity. D is the shear rate, a and b are the two regression coefficients, which are independent of the shear rate. We found that the regression power was highly significant in a wide hematocrit range. Practically, this work deals with the possibility of application to the blood of the Ostwald formula for pseudoplastic flow behavior. We found significant correlations between the two regression coefficients and hematocrit and plasma viscosity, so correcting by calculation the two regression coefficients for standard hematocrit and standard plasma viscosity. This method is simple and can easily be automatically driven by a computer. PMID- 4035210 TI - [Significance of the rheological properties of blood in peripheral vascular pathology]. AB - The rationale of the hemorheologic approach to the pathophysiological knowledge and to the treatment of obstructive arterial diseases of the limbs is discussed in this paper. Indeed, the hemodynamic concepts are the natural frame in which the hemorheologic phenomena have to be considered. Proceeding from this background, it seems evident that the viscosity of blood and its major determinants have a limited role in the regulation of blood flow and pressure gradient through a stenotic artery. On the contrary, viscosity factors are of outstanding significance in the regulation of blood flow in the microcirculation, especially in presence of a reduced perfusion pressure and of exhausted arteriolar vasodilation capacity. Consequently, therapeutic measures capable of modifying one or more viscosity determinants may improve blood flow in the microcirculation of territories related to a stenotic artery. Baseline alterations of viscosity or viscosity determinants may be found in patients with obstructive arterial disease, being classified as primary, associated or secondary to arterial obstruction and ischemic damage. However, the presence of such baseline changes is not relevant to the indication of hemorheologic treatments. PMID- 4035211 TI - [Hemorheological changes during exercise]. AB - It is now necessary to study the macro- and microcirculatory modifications of the organism following the stress. We have devoted our attention to the hemorheological parameters, which have been evaluated in a group of ten sedentary subjects, of fourteen athletes under twenty years of age, and of ten subjects whose age was over thirty, who carry on physical unbroken performance. We have evaluated the modifications of total blood viscosity and of red blood cell deformability after an ergometric test. Our results show that the hemorheological pattern gets worse after strenuous muscular exercise; moreover, the advancing age gets worse the hyperviscosity response. The pathophysiological mechanism which causes the hemorheological disorder is yet unknown, so it is clear the importance of studying the hemorheological balance in order to clarify the pathophysiology of stressed muscular function. PMID- 4035212 TI - [Changes in hemorheological parameters during physical exertion in coronary disease patients]. AB - Blood viscosity and filtrability have been studied in 7 patients with ischemic heart disease and in 9 control subjects before and after maximal stress test on cycloergometer. The diagnosis of ischemic heart disease has been previously established on the basis of the clinical history, abnormal stress test or coronary arteriography. No significant differences were observed, at rest, in the two groups. On the contrary, after stress test blood filtrability resulted significantly reduced in ischemic patients when compared to controls. Blood viscosity resulted substantially unchanged in both groups. Our data may suggest the existence of an alteration in blood filtrability during stress test with a possible pathogenetic role. PMID- 4035213 TI - [Evaluation of blood viscosity and erythrocyte filterability in chronic ischemic heart disease]. AB - In 40 patients suffering from chronic ischemic heart disease (16 with history of myocardial infarction, 10 with unstable angina and 14 with stable angina) and in an equal number of sex-and age-matched control subjects, we have determined plasma and blood viscosity according to RAND et al. using a Wells-Brookfield Micro-Viscometer, shear rate 230 sec-1, and red cell filterability according to REID et al. Significant differences were found in patients suffering from ischemic heart disease, in comparison with the control group, for blood viscosity (p less than 0.01), plasma viscosity (p less than 0.001) and red cell filterability (p less than 0.001). The changes of hemorheological parameters in ischemic heart disease, especially in patients suffering from unstable angina and in those with history of myocardial infarction, point to the opportunity of a pharmacological treatment aiming at improving the district microcirculation. PMID- 4035214 TI - [Effect of hemorheology in the post-operative period]. AB - Very important hemorheological changes characterize the early post-operative period. This research, performed on a group of 10 patients who underwent aorto ilio-femoral revascularization, enables us to observe that these changes are present also in vascular surgery. In fact, plasma fibrinogen, red cells aggregation and deformability, whole blood viscosity, already modified in the pre operative period in patients with peripheral arteriopathy, resulted significantly impaired on the 2nd and 6th day after the operation. Such changes must be considered in order to avoid ischemic consequences on microcirculation, the possible onset of deep vein thrombosis as well as an impairment of the prognosis of vascular operations (early and late reobliteration), and in order to perform an adequate and prophylactic corrective treatment. PMID- 4035215 TI - [Evaluation of principal risk factors, hemorheological and blood coagulation characteristics in arteriosclerosis obliterans in the elderly]. AB - The main risk factors, whole blood filterability, platelet function tests and blood coagulation tests have been evaluated in 68 non-diabetic patients with atherosclerosis obliterans of the lower limbs (stages II and III of Fontaine classification), 34 of geriatric age and 34 of middle age, and in 44 healthy controls of middle age. No different prevalence of risk factors has been found among vasculopathic patients of both ages; platelet function tests and blood coagulation tests are overlapping in the two groups of vasculopathic patients, but they are altered in comparison to healthy controls, whereas whole blood filterability is decreased in both groups of atherosclerotic patients, but mostly in elderly subjects, in whom a therapeutic approach with hemorheological drugs seems more suitable. PMID- 4035216 TI - [The role of erythrocyte deformability in the prolonged bleeding time in liver disease patients]. AB - Hematocrit (Ht), red cell deformability (RCD) determined using a filtration method and bleeding time (BT) have been studied in 28 patients with severe chronic liver disease. Our results show a decrease of Ht (p less than 0.001), RCD (p less than 0.05) and a prolongation of BT (p less than 0.001) not related to the platelet count. Moreover, inverse relationships between Ht and BT (r = -0.52; p less than 0.01) and between RCD and BT (r = -0.54; p less than 0.01) have been found. We conclude that hemorheological alterations, such as decreased Ht and RCD, play an important role in primary hemostasis of patients with chronic liver disease. PMID- 4035217 TI - [Potentials and limitations of viscometry in hemorheological studies]. AB - The problems of viscometric studies are discussed in depth on the basis of the most recent advances in hemorheology. We present here our contribution to the solution of numerous methodological problems. Particular emphasis was set on the problem of optimization and standardization of viscometric techniques for the study of erythrocyte deformation and aggregation. PMID- 4035218 TI - [The hemorheological laboratory in clinical medicine: the value and limitations of its methods]. AB - Hemorheology has been a part of clinical research since precise parameters were determined for the study of flow properties of the blood. A laboratory for clinical hemorheology is nowadays equipped with a variety of instruments, ranging from highly sophisticated to very simple ones, to be used for the measurement of blood viscosity and its main components. The extremely precise viscometers now available for this purpose allow us to take measurements at different shear-rates and can function with small volumes at controlled temperature. The study of blood viscosity goes along with that of its main determinants. Among these there are to be reckoned plasma and serum viscosity, with its main components, i.e. proteins and fibrinogen, and also corpuscular viscosity, i.e. hematocrit and leukocrit. Special consideration is deserved by the methods attempting to evaluate the deformability and the aggregability of the erythrocytes which are, at present, matters of great interest. As far as the deformability of the erythrocytes is concerned, it is to be pointed out how different is the concept of deformability from that of filterability, and how methods directed to the study of the whole blood differ in their significance from those concerning washed red cells. Furthermore, it is to be emphasized that every method has its own questionable points. This is the case also of the methods studying the aggregability of the erythrocytes, a very complex phenomenon which for the time being seems quite difficult to evaluate. PMID- 4035219 TI - [Effects of reduction of blood viscosity at constant hematocrit on the cerebral blood flow]. AB - It is well established that cerebral blood flow (CBF) is low in patients with high hematocrit and is high in anemic patients. An inverse relationship between CBF and hematocrit has been found. Furthermore, if hematocrit is reduced, CBF increases. There is some debate as to whether these observations are due to viscosity or to oxygen carrying capacity of the blood. In order to further elucidate this problem, CBF, blood viscosity and hematocrit were measured in 4 patients with paraproteinemias before and after paraproteins had been removed by plasmapheresis without changes in hematocrit. After plasmapheresis, blood viscosity significantly decreases and CBF increases by a mean of 24.4 ml/100 g/min. Mean arterial blood pressure and hematocrit were not influenced by plasmapheresis. These results indicate that blood viscosity is an important factor in determining CBF. This does not exclude the role of oxygen transport as an associated factor, but it is evident that oxygen transport and blood viscosity are independent variables in the control of CBF. PMID- 4035220 TI - [Significance of hemorheological parameters within the framework of chronic brain disease]. AB - Blood filtration and viscosity were investigated in 32 patients with severe mental deterioration classified on the basis of standard criteria. The group included 17 patients with 'vascular' and 15 with 'cellular' pathogenesis. The results of the study were compared with the data from a large series of 'normal' subjects. Reduced erythrocyte filtration was observed in 70.5% of the patients with vascular pathogenesis and in only 6.6% of those with degenerative conditions. The data on blood viscosity showed less connection between pathological conditions and hemorheological alterations. It is suggested that hemorheological alterations might contribute to the pathogenesis of certain clinical forms of chronic cerebropathy. It is therefore proposed that hemorheological tests should be included among the diagnostic procedures applied to such patients and might also be used in order to establish the appropriate treatment. PMID- 4035221 TI - [Hemorheological parameters in patients with ischemic cerebrovascular disease]. AB - Blood filtration, hematocrit and fibrinogenemia have been evaluated in 80 patients with cerebrovascular ischemic disease and in 60 control subjects. We compared the results between patients and controls and between patients with and without risk factors. The filtration time of all patients and that of patients without risk factors resulted significantly higher than that of controls. The possible pathogenetic implications of our results are discussed. PMID- 4035222 TI - [Hemorheological aspects of diabetic retinopathy]. AB - Among the various factors which contribute to the onset of diabetic retinopathy, modifications both in the retinal vessel walls and the circulating blood volume have been recognized. It cannot be excluded that the indicated hemorheologic alterations and the presence and severity of diabetic retinopathy are independent manifestations, both of them secondary to the metabolic imbalance and not correlated as cause and effect. Nevertheless, the possibility to modify through drugs and an appropriate metabolic control the probably altered hemorheologic situation in diabetes mellitus certainly represents the aim to pursue in order to reduce the severity of diabetic retinopathy. PMID- 4035223 TI - [Hemorheological changes in retinal vein occlusions]. AB - Some hemorheological factors were studied in 34 patients affected by retinal vein occlusion (RVO) and in 25 healthy control subjects. Whole blood viscosity, plasma viscosity, fibrinogen and hematocrit were increased in RVO patients compared with controls. Erythrocyte filterability was reduced in RVO patients compared with controls. However, when evaluating the type of capillaropathy at fluorescein angiography, blood viscosity and plasma viscosity were altered both in patients with and without evidence of capillary non-perfusion. Reduction of red cell filterability showed statistical significance only in patients with capillary non perfusion. This finding suggests that reduced erythrocyte filterability might be a causal factor in the development of capillary non-perfusion in RVO patients. PMID- 4035224 TI - [Lipid composition and fluidity of the erythrocyte membrane in the elderly]. AB - The authors, continuing their studies on hemorheological aspects (blood and plasma viscosity and erythrocyte filtration) and blood flow in the aged, have also studied lipids and fluidity in erythrocyte membrane in aged subjects compared to a group of young control subjects. Such studies underlined a significant rise in plasma and blood viscosity, a decrease of erythrocyte filtration and significant alterations in lipid components and membrane fluidity. The results suggest a correlation between the decreased erythrocyte deformability observed during human aging and the decreased fluidity of the erythrocyte membrane. PMID- 4035225 TI - [Hemorheological changes induced by uremia. Effects of hemodialysis]. AB - Fifteen patients affected by chronic uremia and treated with hemodialysis were studied. The main hemorheological parameters were evaluated in basal conditions and after hemodialytic therapy and were correlated with some hematochemical indices. Although some limitations to the purpose of this study derive from the heparinization of the blood during hemodialysis, the results of this study demonstrate that erythrocyte filtration does not significantly change during the hemodialytic therapy. The only hemorheological parameter altered in the uremic patient is represented by plasma viscosity; this is probably due to the increase of fibrinogenemia in these patients. PMID- 4035226 TI - [Hemodilution, defibrinogenation and plasmapheresis in hemorheology]. AB - Blood and plasma viscosity can be influenced by various therapeutic procedures: among these, that of hemodilution stands out. This can be hypovolemic, normovolemic or hypervolemic; it is hypovolemic if blood subtraction is not followed by a liquid reintroduction, it is normovolemic or hypervolemic if there is a liquid reintroduction of the same or higher quantity than the subtracted blood mass. This method has been considered very favorably by surgery in order to save blood for transfusions. Hypervolemic hemodilution can also be carried out without blood subtraction; a report on this method shows good clinical results and positive hematochemical and hemodynamic effects obtained on 93 peripheral vasculopathic patients at stages III and IV of the Fontaine classification. Plasmapheresis, which would be best called plasma-exchange, consists in the removal of that part of the patient's plasma containing abnormal proteins, immune complexes or toxins, and in its substitution by other colloids or crystalloids. Defibrinogenation is not much employed in Italy, as the most effective drugs, such as ancrod and batroxobin are not available in this country. The good results reported were transitory, due to the rapid appearance of antibodies which can inhibit the effects of these drugs. Nevertheless, there also exist minor fibrinogenolytic drugs. PMID- 4035227 TI - [Effect of sulodexide on hemorheological parameters in a group of patients with peripheral arteriosclerotic vascular disease]. AB - The aim of this study was the evaluation of some hemorheological and metabolic parameters in a group of patients affected by peripheral artery disease treated with sulodexide. A double-blind with cross-over treatment was used. The results demonstrate that sulodexide reduces blood viscosity and triglyceride levels. This action may have a role in order to modify clinical symptoms and evolution of atherosclerosis. PMID- 4035228 TI - [Flunarizine in the treatment of arteriopathies of the legs]. AB - Flunarizine, a long-acting calcium antagonist, was studied in patients with peripheral vascular disease in order to assess its effects on blood viscosity, erythrocyte deformability, platelet activity and some clinical parameters. A randomized double-blind study was performed; all patients were given a standard diet, invited to abstain from smoking and to carry out a regular daily exercise (walking). After a 2-month run-in period the patients were divided into two groups: one was treated with flunarizine 10 mg/day and the other with placebo. The group treated with flunarizine presented marked and significant reduction of erythrocyte filtration time and blood viscosity and an improvement of the treadmill-free interval with a correlation between the parameters considered. PMID- 4035229 TI - [LDL-apheresis in the treatment of familial hypercholesterolemia]. AB - Several non-pharmacological treatments have been tested for homozygous familial hypercholesterolemia and, among these, plasma-exchange has been the most safe and effective. A recent development of this procedure is LDL-apheresis, that is the selective removal of atherogenic LDL and the return to the patient of his own LDL depleted plasma. The method is based on the flowing of hypercholesterolemic plasma on sepharose columns with bound anti-LDL antibodies. PMID- 4035230 TI - [Assay of erythrocyte ATP by chemoluminescence. Protective action induced by pentoxifylline on the depletion of energy from stored erythrocytes]. AB - A new method to measure erythrocyte ATP levels is used. The authors have incubated 6 whole blood samples and 7 samples containing washed red blood cells for 6 h. They measured ATP levels and confirmed an important decrease of the values during the time. If the same samples were incubated with pentoxifylline (1.4 X 10(-4) M), the ATP decrease was less relevant. PMID- 4035231 TI - [Erythrocyte deformability: critical evaluation of the study methods]. AB - The rheological behavior of red cells in macrocirculation and in capillaries is briefly described. The following methods measuring red cell deformability are critically evaluated: a. degree of red cell 'packing' after centrifugation; b. single erythrocyte passage through microchannels (micropipette technique, rigidometer); c. filtration techniques of washed red cells; d. polymicroviscosimetry (paper filtration, filtrometer) and viscosimetry (ektacytometer). It is considered the adequacy of each method in assessing the different factors responsible for the variations of red cell deformability (internal viscosity, surface area/volume ratio, viscoelastic properties of the membrane. PMID- 4035233 TI - [A multicenter study on blood filterability in normal subjects and patients with ischemic vascular disease and diabetes mellitus (preliminary results). Italian Society of Hemorheology Clinical Study Groups]. PMID- 4035232 TI - [Pentoxifylline and arterial hypertension in diabetes mellitus: long-term results in randomized groups]. AB - This follow-up study concerns the use of pentoxifylline (PTX) as antihypertensive drug in randomized diabetic groups. A significant reduction of systolic and diastolic arterial blood pressure has been obtained in diabetic patients treated with PTX alone or with PTX associated to conventional antihypertensive therapy. The normalization of arterial blood pressure was associated to an improvement of erythrocyte filterability and to a reduction of proteinuria. Therefore, pentoxifylline can be considered a good pharmacological approach in the treatment of diabetic hypertension and in the prevention of diabetic renal disease. PMID- 4035234 TI - [Comparison of methods for determining erythrocyte deformability]. AB - We have studied the erythrocyte deformability by means of the filtration technique proposed by Reid et al. and with the new technique proposed by Schmid Schonbein et al. using a Filtrometer MF4. We have studied 50 healthy subjects (24 females and 26 males) aged 25-61 (mean age 34 years). Our results show that slope 80% (SL80) and minimal value (MV) represent the more reliable indexes given by Filtrometer MF4. This instrument gives an exhaustive and automated analysis of erythrocyte deformability. Its results allow us a more extensive knowledge of hemorheological behavior of red blood cells in very low flow conditions. PMID- 4035235 TI - [Blood filterability at various filtration pressures: a study conducted on normal and diabetic subjects]. AB - Using the Reid et al. technique we have evaluated the blood cellular volume (VBC: ml/min) obtained by changing the negative filtration pressure. From the obtained data it is evident that at the three different filtration pressure values (-20, 15 and -10 cm of H2O) the VBC does not distinguish normal from diabetic subjects. Only at the negative pressure of 20 cm of water did the VBC distinguish diabetics, who were subdivided by type and vascular complications. We have also evaluated the relationship between the values of VBC calculated at the pressures of -20 and -10 cm of water. From this study it emerged that the relationship between the two values present in normals is not different from that present in diabetics and in diabetics subdivided by type and vascular complications. PMID- 4035236 TI - Occupational nasal cancer caused by nickel and nickel compounds. PMID- 4035237 TI - Epidemiology of occupational nasal cancer and other occupational nasal problems caused by wood dust. PMID- 4035238 TI - Histopathology of the nasal mucosa in furniture workers. PMID- 4035239 TI - Effects of wood dust exposure and diethylnitrosamine in an animal experimental system. PMID- 4035240 TI - Nasal mucosa changes after exposure to dicumylperoxide. PMID- 4035241 TI - Influence of vapours on the nasal mucosa among industry workers. PMID- 4035242 TI - Formaldehyde. PMID- 4035243 TI - Human nasal mucosa reaction during chilling of the feet. AB - As rhinostereometry, an optical measurement method, allows meticulous studies of changes in nasal mucosa congestion, the mucosal reaction in eight healthy volunteers was studied with this technique before, during and after 20 minutes' chilling of the feet in cold water. In five volunteers there were no observable mucosal reactions. In three volunteers the mucosal congestion changed but not uniformly, and not in such a way that the change could be explained as an effect of chilling of the feet. In four volunteers there was a clearly observable increased nasal secretion. This gives a possible explanation of the increased nasal breathing resistance observed in similar studies using rhinomanometry as the measuring method. PMID- 4035245 TI - Comparison of different coefficients and units in rhinomanometry. AB - The total information of a rhinomanometric measurement is given by the simultaneous registration of flow and pressure during respiration. For characterization of such a measuring curve different methods and units are used. Since no normalized procedure exists up to now, it is difficult to compare measurements of different authors. In this work the relation between various procedures is discussed and methods are given for converting different quantities. The units of the International System are discussed. PMID- 4035244 TI - The mechanisms of systemic symptoms following nasal administration of allergens. AB - A nasal provocation test was performed by consecutively placing allergen discs on the nasal mucosa of patients with pollinosis. This brought easily the systemic symptoms such as cough, periorbital oedema, and urticaria. Similarly, the nasal administration of large doses of the allergen induced a change in the respiratory response in sensitized guinea pigs. These results indicate that nasal mucosa absorbs a high molecular substance such as allergens. PMID- 4035246 TI - Rhinitis leprosary. PMID- 4035247 TI - Occupational allergic rhinitis. PMID- 4035248 TI - Industrial nasal problems. PMID- 4035250 TI - Terminological confusion in evolutionary thought. PMID- 4035249 TI - Localizing genes on human chromosomes. Somatic cell genetics: 30 years later. PMID- 4035251 TI - The Year of Hunger. Cultural conditions and adaptation to famine. PMID- 4035252 TI - [The concept of law in biology. II. Scientific law and determinism]. PMID- 4035253 TI - Dithiocarbamate induced teratogenesis in frog embryo. PMID- 4035254 TI - [Sleep disorders in growing children. Cross-sectional study of 643 healthy subjects]. AB - The existence of sleep disorders was investigated in 643 healthy children of ages ranging from 3 to 14 years, resident in Latina, city of the central part of Italy. PMID- 4035255 TI - [Tolosa-Hunt syndrome. Observations in 11 cases]. AB - The authors report 11 cases of Tolosa-Hunt syndrome, a painful ophthalmoplegia due to an aspecific, benign, steroid-responsive inflammation of the cavernous sinus. Other causes of painful ophthalmoplegia, diagnostic findings and etiological hypothesis are discussed. PMID- 4035256 TI - [New proposals for the treatment of multiple sclerosis. Preliminary study]. AB - The authors carried out therapeutic preliminary trial on 8 Multiple Sclerosis patients traited by Azathioprine and corticosteroids in alternated administration during a period of 8-24 months. Treatment was efficacious in all examined subjects and tolerance was very good. The authors discuss upon the use of long term immunosoppressive therapy in the different clinic types of multiple sclerosis. PMID- 4035257 TI - [Post-traumatic hydrocephalus]. AB - Post-traumatic hydrocephalus is a complication of cranio-cerebral injuries and can manifest itself through different clinical syndromes. These include obtunding, a tetrad composed of psychomotory delay, memory loss, motility disturbances and sphincter incompetence, and unusual symptoms which comprehend emotional disturbances. Intracranial pressure monitoring, lombo-ventricular infusion test, in addition to neuroradiologic exams, are necessary in order to decide wether or not to derivate a post-traumatic hydrocephalus; neuropsychologic tests complete these investigational methods. The post-traumatic hydrocephalus bearer patient's recovery is always problematic when an important parenchimal damage exists. When a NPH (normal pressure hydrocephalus) is found the shunting operation is always indicated. However it is difficult to take a decision when the patient has a normal liquoral pressure but is too wounded to show a NPH or when he has an atypical clinical feature. PMID- 4035258 TI - [Epidemiology of the neurologic manifestations of alcoholism. Preliminary study in Lombardy]. AB - Epidemiologic data concerning frequency and distribution of alcoholism in widespread geographic areas in Italy as well as in other countries, are missing. The aim of this research is the evaluation, of global admissions in general public hospitals of Lombardy, during the year 1976, concerning all patients suffering neurologic complications from alcoholism. The neurologic annual ratio of alcoholic complications (N.A.I.A.C.) calculated for Lombardy is 247/100.000 people. The N.A.I.A.C. is a useful descriptive epidemiologic estimation for many statistical pourposes. The present study is introductive and is going to fulfilment and control in the next future. PMID- 4035259 TI - [Anatomo-functional organization of human movement]. AB - The authors analyze both anatomical and physiological aspects of human movement in the light of biological evolution of the nervous system. PMID- 4035260 TI - Early stages of nodular transformation of the B6C3F1 mouse liver induced by choline deficiency. AB - The B6C3F1 strain of mice is prone to develop liver nodules as animals grow older. This spontaneous tumor development is enhanced by dietary lipotrope deficiency. The present studies were performed to evaluate the liver of the B6C3F1 mice in early periods of lipotrope deficiency and before the nodules appear. Mice were fed high levels of dietary fat (cotton seed oil or beef fat) without choline or vitamin B12. The livers of these mice were compared with those of mice subjected to partial hepatectomy or dietary phenobarbital both of which enhance liver nodule formation. The ability of putative preneoplastic hepatocytes to exclude parenteral-administered iron was used to detect this eventual phenotype. A lipotrope-deficient condition was established which typically exhibited fatty liver and increased cell proliferation, the latter measured by autoradiography. In the time periods evaluated the lipotrope-devoid diets were not sufficient to induce nodular or putative preneoplastic lesions. An excessively high activity of p-nitroanisole-O-demethylase and a single small fatty nodule were obtained when phenobarbital was added to the lipotrope deficient diet. Scattered eosinophilic hepatocytes were seen in every experimental group when the histologic slides were stained for iron pigments, but their biologic significance in the present experiments could not be established. Under the conditions of this study, the liver of the B6C3F1 strain of mouse exhibited only minor indications of future tumor development. PMID- 4035261 TI - Morphologic changes in the gastric mucosa of rats and dogs treated with an analog of prostaglandin E1. AB - American Cyanamid compound CL 115,574, a synthetic analog of prostaglandin E1, is active orally in inhibiting gastric acid secretion and in protecting against gastric ulcers induced by stress, ethanol, and nonsteroidal anti-inflammatory drugs. CL 115,574 was administered to rats for 6 months and to dogs for 1 year. Diarrhea occurred in both species and transient hyperthermia was observed in dogs. In rats, the only gross finding related to treatment was limited to the gastric mucosa and consisted of a dose-related widening of the cuticular ridge in the mid (2 mg/kg/day) and high (20 mg/kg/day) dose groups. Microscopically, there was a proliferation of the cuticular ridge stratified squamous epithelium. Morphologic findings in the dogs showed a multifocal proliferation of the foveolar epithelium in the pyloric antrum. Neither species had atypical cellular changes associated with the proliferative process. Furthermore, the changes in the dog consisted of well differentiated cells and occurred without pseudostratification of cells and increased mitotic activity. The "pseudoproliferative" character of these changes may be the result of a prolonged life span of most cell types of the gastric mucosa. These tissue adaptations reflect a true manifestation of the cytoprotective effect of prostaglandin E1 on the gastric mucosa. PMID- 4035262 TI - Neoplasia induced in male rats fed lead acetate, ethyl urea, and sodium nitrite. AB - Sprague-Dawley rats were exposed to 0, 26, or 2600 ppm lead as lead acetate in drinking water for 76 weeks. At 28 weeks of lead exposure, a portion of each group was exposed simultaneously to 6.36 g/kg ethyl urea (EU) and 2.0 g/kg sodium nitrite (NaNO2) for a duration of 20 weeks, and then continued an additional 28 weeks on standard diet free of EU and NaNO2. The animals were observed for incidence, latency, and distribution of tumors. Rats exposed to 2600 ppm lead alone had 81% renal tumors, while rats given 2600 ppm lead in combination with EU/NaNO2 had a 50% incidence. Renal tumors did not occur in the EU/NaNO2 only or EU/NaNO2-26 ppm lead groups. The major tumor type found in EU/NaNO2-exposed rats was lymphosarcoma. Lead did not appear to be syncarcinogenic to the activity of ethylnitrosourea, the carcinogen formed by oral exposure to EU and NaNO2. The lead-induced renal neoplasms were histologically similar to those which occur spontaneously in man and, therefore, may serve as an animal model to study human disease. PMID- 4035263 TI - [Diagnostic possibilities of computer tomography in spinal and paraspinal space occupying lesions]. AB - Characteristic CT findings of intramedullary, intradural and epidural as well as of vertebragenic and paraspinal tumours are described, basing on literature and on the authors patient material. The value of CT is discussed and compared with that of other imaging modalities. Attention is also drawn to the value of i.v. application of contrast medium and of primary or secondary CT myelography. PMID- 4035264 TI - The clinical value of computerized axial tomography in patients without focal neurological features. AB - 74 randomly selected patients with non-focal cerebral symptoms and a normal neurologic examination were referred from neurologic departments to CT scan of the brain. 29 patients had generalised epilepsy of long duration. In 26 patients (90%) with epilepsy the CT scan was normal. 2 patients (7%) had cerebral atrophy, 1 (3%) showed porencephaly (?) 41 (91%) of the patients without epileptic features had a normal CT scan. 4 (9%) presented cerebral atrophy. In this survey, CT scanning did not contribute to a focal diagnosis in patients with diffuse cerebral features. PMID- 4035265 TI - [Bolus geometry in various central and peripheral contrast medium applications: study with serial CT using non-ionic contrast media]. AB - Measurements of concentration in 27 patients with a calibrated Serio-CT yielded for the intravasal contrast medium bolus maximum a value of approx. 23 mg I/ml for the a. carotis with central injection and approx. 14 mg I/ml for the a. iliaca with peripheral injection. 7 invasive measurements were performed at the bifurcation of the aorta, yielding a value of 12.5 mg I/ml with peripheral injection. In all these cases, 40 ml nonionic contrast medium (Iohexol) with an iodine content of 350 mg I/ml were applied. The average bolus half-life was 9.5 sec. measured at the carotid artery, 11.5 sec. at the a. iliaca, and 7 sec. at the bifurcation of the aorta. Differences in bolus geometry were not seen on comparing arterial injection with cava superior injection; likewise, there were no differences between peripheral injections at various speeds. Animal experiments reported in literature show that these observations can be mainly ascribed to vascular dilatation in the minor circulation produced by the contrast medium. PMID- 4035266 TI - [Reduction of patient dose with maximum assurance of image quality]. AB - Four methods of reducing the patient dose are reviewed. Without doubt, the patient dose can be considerably reduced by relatively simple means: With rare earth screens by a factor of 2-4 compared with a CaWO4 universal screen (1 mR) and in some cases by a factor of 1.5-2 with prefiltration. A more complicated and expensive method is the 100 mm spotfilm technique. This permits a dose rate reduction by a factor of 10 compared with a CaWO4 universal screen or by a factor of 5 compared with a universal system with rare-earth screens. In the wide ranging field of digital radiography, the possibilities of dose reductions by means of digital processing of conventional film screen exposures are investigated. PMID- 4035267 TI - [Diagnosis of a colonic lipoma with computer tomography]. AB - This report describes the case history of a woman with a large submucosal tumor in the ascending colon detected by barium enema radiography. Computed tomography (CT) identified the tumor as a submucosal lipoma characterised by its homogeneous fat-equivalent density with a CT number of -95 HU. This case proves that CT can be a definite diagnostic modality for differentiation between gastrointestinal lipomas and other solid or cystic tumors. PMID- 4035268 TI - Histopathological data on six cases of hypothyroidism accompanying muscular chronic disease. AB - This study was carried out on 6 patients with myxedema that showed major muscular alterations. Light and electron microscopic examinations of the striated muscle structure revealed myxedematous myopathy lesions. Considering the existence of several hypotheses regarding the pathogeny of muscular alterations, the authors discuss the likelihood of a myogenic syndrome induced by an immunity deficit in hypothyroidism. PMID- 4035269 TI - Investigation of thermic transition and renaturation of high polymerized DNA extracted from thyroid nodule. AB - The study was carried out on 16 cases of mixed thyroid hypertrophy in which total or partial thyroidectomy was performed. Fragments collected intraoperatively from the thyroid nodule were used for extraction of high polymerized DNA. At the same time with quantitative evaluation of DNA, RNA and proteins were also assayed. The thermic transition mean temperature of the DNA extracted from the thyroid nodule is compared to other standards (DNA-HP-standard, calf thymus DNA, normal leukocytic DNA) and the thermic transition curves are presented. Hyperchromicity after thermic denaturation and renaturation is analysed and expressed in per cent values. PMID- 4035270 TI - 47,XXX/48,XXXX in a retarded three year old girl with multiple somatic anomalies. AB - A 3-year old girl with 47,XXX/48,XXXX caryotype is presented. She suffers from psychomotor retardation, dolichocephaly, malformed ears, "a false air of trisomy 21", malformation of the legs, obesity. The authors discuss briefly the available data on the triplo and tetra X phenotype and syndromes. PMID- 4035271 TI - [Induction and transplantability of ferridextran tumors in inbred strains of Rattus norvegicus]. PMID- 4035273 TI - [The present status and perspectives in the diagnosis of tumors using microwaves]. PMID- 4035272 TI - [Properties and excretion of Bromsulfan labeled with 131I]. PMID- 4035274 TI - [The significance of determining the daily blood glucose profile for the evaluation of compensation in diabetes]. PMID- 4035275 TI - [Endoscopic retrograde cholangiopancreatography (ERCP) in the diagnosis of congenital cystic dilatations in the biliary system]. PMID- 4035276 TI - [Endoscopic retrograde cholangiopancreatography (ERCP) in the diagnosis of cystic duct stumps after cholecystectomy and concurrent bile duct lithiasis]. PMID- 4035277 TI - Analysis of vanillylmandelic and homovanillic acids in urine using solid phase sample preparation and high pressure liquid chromatography with electrochemical detection. AB - A rapid, simple and specific method for quantification of vanillylmandelic acid (VMA) and homovanillic acid (HVA) in urine is described. The method is suitable for routine use and may include other organic acids in human urine. PMID- 4035279 TI - A method for the quantification of cartilage proteoglycan structures liberated to the synovial fluid during developing degenerative joint disease. AB - An enzyme linked immunosorbent assay for the quantification of proteoglycans or proteoglycan fragments in biological fluids is presented. The assay has been used to determine concentrations of articular cartilage proteoglycans and/or fragments thereof in synovial fluid in early stages of osteoarthrosis. Osteoarthrosis was induced in one knee joint of nine German wire haired pointers by transection of the anterior cruciate ligament. All dogs developed osteoarthrosis in terms of macroscopic as well as microscopic criteria. Attempts were made to aspirate synovial fluid, prior to surgery and at various times in the postoperative period, from the joint operated on as well as from the contralateral joint. Concentrations of proteoglycans (fragments) of one type of aggregating proteoglycan were significantly higher in the synovial fluid samples from the joint operated on compared to the contralateral joint (p less than 0.001), while the difference observed when the other type of aggregating proteoglycan was used as the test antigen was less significant (p less than 0.05). The concentration of proteoglycans (fragments) in synovial fluid samples from joints operated on was significantly higher after the operation when compared with the preoperative concentration (p less than 0.001). No correction has been made for the increased dilution due to hydrops of the joints operated on. PMID- 4035278 TI - Abnormal conjugated dopamine levels in patients with normoprolactinaemic amenorrhoea and in insulin-dependent diabetic patients. AB - We determined the circulating dopamine levels in 17 patients with insulin dependent diabetes mellitus (IDDM), of whom eight had amenorrhoea (DM-AM) and nine were normally menstruating (DM). Seven non-diabetic women with normoprolactinaemic, normogonadotrophic secondary amenorrhoea (AM) and nine normally menstruating women (controls) were studied. In all subjects basal blood concentrations of free dopamine (f-DA), conjugated dopamine (c-DA), epinephrine (E), norepinephrine (NE), prolactin (PRL), luteinizing hormone (LH), thyroid stimulating hormone (TSH) and oestradiol-17 beta were determined and all subjects, except for three AM patients, had a Metoclopramide test performed for measurements of f-DA, c-DA, PRL, LH and TSH. Plasma c-DA was significantly (p less than 0.05) increased in patients with amenorrhoea compared to the respective control groups. In diabetic patients c-DA levels were significantly (p less than 0.05) lower compared to controls. The ratio between basal f-DA and c-DA concentrations was significantly (p less than 0.01) higher in diabetic patients compared with non-diabetic patients. After Metoclopramide stimulation DM-AM patients showed a significant (p less than 0.05) rise in c-DA, whereas this was not seen in other groups. DM-AM patients had significantly (p less than 0.05) lower basal PRL and LH levels than DM patients and controls. In addition DM-AM patients had a significantly (p less than 0.05) lower PRL response to Metoclopramide compared with DM patients. There were no significant correlations between catecholamines and basal as well as Metoclopramide stimulated pituitary hormones. This study suggests that the abnormal pituitary hormone secretion in patients with amenorrhoea may in part be caused by an increased dopaminergic activity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4035280 TI - Fast atom bombardment mass spectrometry in the diagnosis of cerebrotendinous xanthomatosis. AB - Urine from a patient with cerebrotendinous xanthomatosis (CTX) was extracted with a Sep-Pak C18 cartridge and the extract was analysed by fast atom bombardment mass spectrometry. The spectra indicated the presence of glucuronidated bile alcohols with four to seven hydroxyl groups. The method is simple and rapid and is suggested as an aid in the diagnosis of CTX with possible application to prenatal diagnosis. PMID- 4035281 TI - Plasma adrenaline and noradrenaline during mental stress and isometric exercise in man. The role of arterial sampling. AB - Plasma adrenaline and noradrenaline were measured in arterial blood and in forearm venous blood during isometric exercise and during a mental stress test. In both conditions arterial plasma adrenaline increased significantly, whereas arterial plasma noradrenaline remained unchanged. During isometric exercise the increase in plasma adrenaline was greater in venous blood from the exercising arm than from the resting arm. The extraction of adrenaline in the forearm was greater in the resting than in the exercising arm. Venous plasma noradrenaline showed a rebound phenomenon after isometric exercise and tended to decrease during the mental stress test. The results indicate that it is preferable to measure arterial concentrations of adrenaline as an indicator of sympathoadrenal activity rather than venous concentrations since the extraction of adrenaline in forearm might not be constant. It is suggested that a selective increase in arterial plasma adrenaline as opposed to an increase in both plasma adrenaline and noradrenaline may indicate a selective increase in sympathoadrenal activity in visceral organs. PMID- 4035282 TI - The predictive value of bronchial histamine challenge in the diagnosis of bronchial asthma. AB - A prospective survey aiming to study the predictive value of bronchial histamine challenge was performed on 151 patients with a forced expiratory volume1 (FEV1) above 60% of predicted. According to variations in peak expiratory flow rate (PEFR) and medical history the patients were classified as asthmatics (n = 97) or non-asthmatics (n = 54). The diagnostic properties of the challenge were calculated using the statement of Baye. Considering PC20 values below 4.00 mg/ml as positive, the predictive value of a positive test was about 0.80 and the predictive value of a negative about 0.76. When PC20 was below 0.125 mg/ml the predictive value of a positive test was 1.00, but an increase in PC20 in the range from 4.00 to 16 mg/ml did not increase the predictive value of a negative test. In this study the prevalence of asthma was about 0.6. We therefore conclude that bronchial histamine challenge is a valuable test for detection and exclusion of bronchial asthma, when the prevalence of the disease is high. In populations with a lower frequency of bronchial asthma the diagnostic value of a positive bronchial challenge will be negligible. PMID- 4035283 TI - An enzyme linked immunosorbent assay (ELISA) for measurement of human serum thyroglobulin. Evaluation of the influence of thyroglobulin auto-antibodies. AB - The aim of the study was to develop an enzyme linked immunosorbent assay (ELISA) for measuring thyroglobulin (Tg) in human serum and to evaluate the influence of serum thyroglobulin auto-antibodies (TgAb) on the ELISA. The sensitivity of the ELISA was 2.1 micrograms/l. Serum Tg levels in healthy controls were from less than 2.1 to 55.5 micrograms/l (n = 46) (95% reference range). With serum Tg concentrations between 19.6 to 90 micrograms/l the within-assay coefficient of variation (CV) was from 4.5 to 6.6% (n = 12) and the between-assay CV from 8.5 to 10.5% (n = 6). The recovery from 20 to 89 micrograms Tg/l serum was from 93 to 101%. There was significant correlation between serum Tg concentrations measured by the ELISA and a RIA method in healthy controls (r = 0.85, n = 46, p less than 0.001) and in patients with differentiated thyroid carcinoma (r = 0.97, n = 28, p less than 0.001). The TgAb interfered with the serum Tg determination both in the ELISA and in the RIA method. The assay is simple and easy to perform, and the equipment is inexpensive and useful for large-scale serum Tg measurements as an alternative to RIA. PMID- 4035284 TI - A simplified method for estimating mean values of multiple specimens. AB - Determination of the correct average content of a constituent in multiple specimens requires measurements of concentration and volume of each specimen. We have evaluated a simplified method by which the mean content is estimated from one concentration determination and the total volume of the specimens. The greatest possible deviation from the correct mean value can be estimated, and is shown in diagrams. It is demonstrated that a simplified method can often be used with little loss of accuracy. The method is exemplified by measurements of lipid and biliary acids in faeces from healthy subjects and from patients with Crohn's disease. PMID- 4035285 TI - Crohn's disease. Diagnostic procedures and problems. AB - Two hundred and fourteen patients with Crohn's disease (CD) were investigated by radiological methods, endoscopy, and histological examinations of multiple biopsy and surgical specimens. Radiological lesions suggestive of CD were found in all patients with small-bowel disease but in less than half of those with large-bowel CD. Endoscopic findings were conclusive in 36% of patients with small-bowel disease, in 91% of those with small- and large-bowel disease, and in 86% of those with CD of the large bowel. Histological examinations of biopsy specimens were conclusive in less than one third of the patients. Histological examination of operative specimens, however, was conclusive in 90-100% of all patients. In 43 patients initially diagnosed as having ulcerative colitis, abdominal pain was less frequent, but diarrhea and visible blood were more frequent as initial symptoms. Of these patients, 21 had combined small- and large-bowel disease at the end of the observation time. In intestinal CD, multiple biopsy specimens may disclose Crohn-specific lesions even in endoscopically normal mucosa at a distance from visible lesions. PMID- 4035286 TI - Crohn's disease. Clinical manifestations. AB - Two hundred and fourteen patients with Crohn's disease (CD) consecutively admitted during a 5-year period were observed for a mean of 9 years (range, 0-35 years). Sixty-five per cent had their initial symptoms between 10 and 30 years of age and 9.2% after the age of 50 years. The CD diagnosis was delayed for more than 10 years in 8% (mean, 4.5; range, 0-31 years). Large-bowel involvement was seen in 82.5% and was the only localization of the disease in a fourth of the patients. Recurrent abdominal pain occurred in two-thirds of patients with ileal or ileocolic disease. Acute abdominal pain was the cause of laparotomy in 14% of the patients with ileocolic CD. Diarrhea and rectal bleeding occurred significantly more often in colonic CD, whereas fistula complicated ileocolic disease more often than isolated involvement of small or large bowel. Associated extraintestinal diseases were seen in 117 patients (55%), most frequently related to colonic involvement (joint disease, 21%; eye, 12%, skin, 8%). Of 26 patients (12%) with liver pathology, 10 patients had amyloid deposits. Amyloidosis was diagnosed in altogether 12 patients (6%). PMID- 4035287 TI - Epidemiology of polyps in the rectum and sigmoid colon. Histological examination of resected polyps. AB - In an endoscopic screening study of rectosigmoidal polyps in a defined normal population aged 50-59 years, polyps 5 mm or larger in diameter were removed by diathermic snare resection for histological examination. Histological examination was possible in 50 of 55 polyps removed during colonoscopy from 27 men and 17 women. Of these polyps 41 (82%) were adenomas--12 with moderate dysplasia, 1 with severe dysplasia, and 2 with intramucosal carcinoma. In addition, a small ulcerating carcinoma, Dukes stage A, was found. A greater extent of dysplasia was found in rectosigmoidal adenomas in women, whereas more polyps were found in both distal and proximal parts of the colon among men. The size of adenomas and degree of dysplasia were unrelated to color of the lesions. PMID- 4035288 TI - The serum 14C-triolein/3H-oleic acid assimilation test for differential diagnosis of maldigestion and malabsorption. AB - In 125 consecutive patients the measurement of serum radioactivities after simultaneous ingestion of 14C-triolein and 3H-oleic acid was investigated as a test of lipid assimilation. The sum of the 2-h and 4-h concentrations of 14C in serum (se(2 + 4)14C) was most useful as an index of lipid assimilation, and the 2 h serum 3H/14C ratio (se-3H/14C) reflected lipid digestion. Normal values were se(2 + 4)14C greater than or equal to 1.0% of the dose ingested per litre serum and se-3H/14C less than 1.3. Se(2 + 4)14C correlated significantly with faecal fat (r = -0.56, P less than 0.001) and indicated malassimilation in 26 of the 50 patients with a faecal fat excretion greater than 7 g/day. False-negative values appeared mainly in the patients with moderate steatorrhoea and gastrointestinal anastomoses. Only one false-positive se(2 + 4)14C value was found. Se-3H/14C was abnormal in 24 of the 34 patients with maldigestion with 2 false-positive results. When the results of se(2 + 4)14C and se-3H/14C were combined, the predictive value of the test result 'normal lipid assimilation' was 0.75, that of the test result 'maldigestion' was 0.93, and that of 'malabsorption' was 0.71. It is concluded that the serum 14C-triolein/3H-oleic acid assimilation test is convenient and inexpensive and may be useful when quantitative faecal collections are not available. PMID- 4035289 TI - Liver retinoids and retinol esterification in fetal and pregnant rats at term. AB - Retinol esterification in fetal rats and their mothers at term was studied in liver microsomes. The esterification rate was 0.28 +/- 0.05 nmol ester formed per milligram protein per minute, a value somewhat lower than that found in their mothers (0.44 +/- 0.11). The fetuses had significant amounts of liver retinoids. Analysis by high-performance liquid chromatography showed that the retinoid store consisted mainly of retinyl ester both in fetal and adult rat livers, but the fetal livers had higher percentages of free retinol and retinyl oleate than the adult livers. The presence of retinol esterification and a retinyl ester store in fetal rat liver at term is in accordance with the view that retinol brought to liver on retinol-binding protein can be taken up and retained there. PMID- 4035290 TI - Studies of intestinal lymphoid tissue. IX. Dose-dependent, gluten-induced lymphoid infiltration of coeliac jejunal epithelium. AB - Jejunal biopsy specimens from coeliac patients who had received small, oral doses (100-1500 mg) of a peptic-tryptic gluten digest were analysed by morphometric methods. An increase in the total number of surface epithelial lymphocytes, maximal at 12 h after challenge, was dose-dependent, the mean percentage rise at this time being 53% (p less than 0.005), 44% (p = 0.01), and 25% (p greater than 0.05) with 1500, 1000, and 500 mg of gluten digest, respectively. This effect was not accompanied by any increased mitotic activity or blast transformation among the infiltrating lymphocytes, nor was there any demonstrable alteration in mucosal structure-that is, reduction in surface or increase in crypt epithelial volumes. The results of this controlled morphometric analysis indicate that oral gluten challenge causes an increase in the lymphocyte population of surface epithelium in coeliac disease but that this effect does not necessarily result in mucosal damage. PMID- 4035291 TI - Glycoprotein secretion from mouse gallbladder principal cells after chronic variation in parasympathetic activity. A morphometric study after vagotomy and cholinergic superstimulation. AB - Principal cells of mouse gallbladder epithelium were subjected to quantitative electron microscopic investigation either after superstimulation with pilocarpine for 12 days or 6 weeks after vagotomy at different levels. Cholinergic superstimulation caused a slight hypertrophy of the principal cells, whereas different types of vagotomy induced hypotrophic changes. In the superstimulated animals there was decreased sensitivity to single-dose stimulation with pilocarpine. In contrast, a supersensitivity was recorded in mice subjected to vagotomy. It is concluded that the parasympathetic nervous system is of importance for the regulation of glycoprotein secretion from mouse gallbladder principal cells. The demonstrated vagotomy-induced super-sensitivity may be responsible for an increased glycoprotein release, which in turn may be involved in the formation of gallstones occurring after truncal vagotomy in man. PMID- 4035292 TI - Pancreatic enzyme synthesis in pancreatic disease. AB - In a prospective evaluation of patients suspected of having chronic pancreatitis, synthesis of pancreatic enzymes was measured by means of the incorporation of selenium-75-labelled methionine into the proteins of duodenal aspirate during stimulation of pancreatic secretion with secretin (1 CU X kg-1 X h-1) plus cholecystokinin (CCK) (1 IDU X kg-1 X h-1). The rate of pancreatic enzyme synthesis was increased in patients with chronic pancreatitis. Measurement of pancreatic enzyme synthesis was more sensitive in the detection of chronic pancreatitis than either the bicarbonate or the trypsin secretory response to secretin plus CCK. A combination of the bicarbonate secretory response with measurement of the rate of enzyme synthesis provided a positive predictive power of 100% when both tests were abnormal and a negative predictive power of 100% when both tests were normal, so that the combined test can be recommended both for excluding and confirming the presence of chronic pancreatitis. PMID- 4035293 TI - Mineral-metabolic side effects of low-dose antacids. AB - Mineral-metabolic side effects of a low dose of a conventional Al-Mg antacid were examined in 10 healthy volunteers, who were given one antacid tablet after the 3 main meals and at bedtime (buffering capacity, 120 mmol/day) for 4 weeks. Compared with the pre-medication state, the following changes of statistical significance occurred during antacid ingestion: increase in urinary excretion of magnesium, calcium, and aluminum; decrease in urinary excretion of phosphate; increase in maximal renal phosphate reabsorption (Tm PO4/GFR); and increase in serum concentration of aluminum. Most of the changes were normalized 3-4 days after cessation of antacid medication. There was no change in intestinal absorption of calcium. The fact that even this low dose of antacids can provoke measurable changes in mineral metabolism, including aluminum absorption, is noteworthy, although we did not see any clinical symptoms from the biochemical changes. PMID- 4035294 TI - The effect of ranitidine on the absorption of food cobalamins. AB - The effect of the histamine H2-receptor antagonist ranitidine on the absorption of food cobalamins was investigated in 20 healthy volunteers randomized to treatment with ranitidine or placebo for 1 week. Liver homogenates containing cobalamins labelled in vivo with cobalt-57 was obtained by repeated injections of 57Co-labelled cyanocobalamin in rabbits. Test doses (0.37 nmol) of the 57Co labelled liver cobalamins were administered orally together with 51CrCl3 and carmine red, and the absorption of 57Co-labelled cobalamins was assessed from the ratio of the two isotopes in the stool collection that had been coloured by the carmine red. There was no significant difference in the mean absorption before (47.4%) and after (50.7%) the treatment. PMID- 4035295 TI - Mandibular osteomas in colorectal cancer. AB - Orthopantomography of the mandible was carried out on 50 patients with colorectal cancer without known familial disposition. Twelve patients (24%) had osteomas, as against 5% in the control group (P less than 0.001). Since an increased occurrence of mandibular osteomas has earlier been demonstrated in cases of familial polyposis coli and the family cancer syndrome, we must conclude that genetic factors are presumably of more importance in the development of colorectal cancer than previously assumed. PMID- 4035296 TI - Continuous computerized determination of gastric bicarbonate secretion in man. AB - A method for continuous determination of gastric bicarbonate secretion in man has been developed. A computer-based system calculated the total bicarbonate secretion every 30 sec throughout the experiment on the basis of the continuously recorded pH and Pco2 measurements. A high gastric perfusion rate facilitated the identification of duodenogastric reflux, which was observed as rather short-lived spikes on the curves. The contribution of alkaline saliva to the measured gastric bicarbonate secretion was minimized by continuous salivary suction and was corrected for after determining amylase in the gastric aspirate. Validation of the measuring system, by introducing bicarbonate in the range of 50-400 mumol into the stomach, demonstrated a correlation value of 0.91 (p less than 0.001) between added and recovered bicarbonate. Basal gastric bicarbonate output in seven healthy subjects was 379 +/- 105 mumol/h (mean +/- SEM). Intragastric instillation of 16,16-dimethyl prostaglandin E2 in five subjects resulted in a fourfold increase in gastric bicarbonate output. PMID- 4035298 TI - Monoclonal antibodies recognizing a neoantigen of poly(C9) detect the human terminal complement complex in tissue and plasma. AB - The terminal complement complex (TCC), consisting of C5b, C6, C7, C8, and C9, contains neoantigens that are absent from the individual native components. Neoantigens are present both in the membrane-bound (MAC) and the fluid-phase (SC5b-9) complex. The present study describes production of monoclonal antibodies against neoantigens of both forms of the TCC. A convenient screening and detection system, based mainly on enzyme-linked immunosorbent assays, crossed immunoelectrophoresis with autoradiography, and affinity chromatography with subsequent sodium dodecyl sulphate-polyacrylamide gel electrophoresis including immunoblotting, is described in detail. Two monoclonal antibodies were specific for a neoantigen located in the poly(C9) moiety of the TCC. One of these antibodies, MCaE11, was used for immunohistochemical detection of MAC in tissue and for quantification of the fluid-phase TCC in ethylenediaminetetraacetic acid plasma. PMID- 4035297 TI - Oral water causes emptying of the human gallbladder through actions of vagal stimuli rather than motilin. AB - A drink of water was found to cause partial emptying of the human gallbladder in parallel with the release of motilin. The water-induced effect on the gallbladder was abolished by atropine, whereas the release of motilin remained unchanged. Exogenous infusions of porcine motilin aimed at achieving either a physiological or a pharmacological plasma motilin increment were both without effect on gallbladder dynamics as compared with saline infusions. It is concluded that the water-induced gallbladder emptying is vagally dependent. Furthermore, the results suggest that motilin does not cause gallbladder emptying in man. PMID- 4035300 TI - Increased critical stimulus duration: vulnerability or episode indicator? AB - Increased critical stimulus duration among nonpsychotic subjects with Minnesota Multiphasic Personality Inventory 2-7-8 profiles in the Merritt and Balogh letter discrimination procedure is consistent with the view that this abnormality might be a vulnerability indicator for a poor prognosis, chronic type of schizophrenia. However, the procedure that Merritt and Balogh used to measure critical stimulus duration is likely to involve higher load on processing capacity than the procedure used by Braff and Saccuzzo with patients who showed schizotypal personality disorder. Thus, consistent with our hypothesis, the Merritt and Balogh procedure appears more likely to detect a deficit among persons at risk for schizophrenia than procedures that involve little or no demand on processing capacity. PMID- 4035299 TI - Critical stimulus duration: schizophrenic trait or state? AB - Recent evidence challenges the conclusion of Nuechterlein and Dawson (1984) that a critical stimulus duration (CSD) may be a likely candidate for a state marker of schizophrenia. We summarize the results of three different CSD investigations which used differing schizotypic detection criteria and report that the Minnesota Multiphasic Personality Inventory (MMPI) 2-7-8 schizotypic profile identified vulnerable college students with a CSD deficit. On the basis of these data, we suggest that the CSD task should not be considered a state marker of schizophrenia and may qualify as a trait marker of a specific subgroup of schizophrenia. PMID- 4035301 TI - "Negative symptoms": conceptual and methodological problems. AB - Research into the so-called negative symptoms of schizophrenia is plagued by often ignored problems in item identification, scale selection, quantification, clinical assessment process, and symptom (and, probably, causal) nonspecificity. Neither a negative symptom syndrome per se nor the recent rating scales designed to measure it have been validated, although some data useful in this regard have been presented for the scales. Since no criterion against which to validate these scales exists, construct validation is needed. The construct of negative symptoms, as defined by its hypothesized empirical relationships with other variables, and the procedures used to measure it must be validated simultaneously and gradually through a programmatic series of studies. In the meantime, research results pertaining to negative symptoms should be interpreted with considerable caution. PMID- 4035302 TI - An empirical test of a Kraepelinian vs. a Bleulerian view of negative symptoms. AB - Confirmatory factor analysis was used to test a Kraepelinian vs. a Bleulerian interpretation of negative symptoms. The former focuses on absolute loss of functioning, while the latter emphasizes the qualitative loss of organization. Contrary to expectation, neither theory was confirmed, but rather three independent factors emerged: apathy, psychomotor retardation, and loss of goal. The implications of these findings for subtyping schemes and the conceptualization of negative symptoms are discussed. PMID- 4035303 TI - Positive and negative schizophrenic symptoms, attention, and information processing. AB - This study was concerned with the relationship between attentional and information-processing deficits and positive vs. negative symptoms in schizophrenia. Sixteen schizophrenic patients, rated for extent of positive and negative symptomatology, 17 depressed patients, and 31 normal control subjects were tested on a measure of distractibility and ability to process under information overload. To establish the validity of our measures, schizophrenic patients were compared with depressed patients and with normal control subjects. Lowered processing capacity appeared to be specific to schizophrenia, although the specificity of differential distractibility was less clear. For schizophrenic patients, positive symptoms were related to distractibility, whereas negative symptoms were associated with lowered processing capacity. These findings were interpreted as supporting Crow's (1981) hypothesis that the two clinical syndromes reflect independent pathological processes. PMID- 4035304 TI - Symptomatic and neuropsychological components of defect states. AB - The distinction between positive and negative symptoms has gained prominence in schizophrenia research, but the construct has not been unequivocally validated. The authors report preliminary findings of investigations in which symptomatic and neuropsychological assessments were conducted in a sample of 32 chronic schizophrenic inpatients. Three distinct clusters of symptoms were identified in correlative analyses. One cluster of symptoms (alogia, attentional impairment, positive formal though disorder, and bizarre behavior) appeared to reflect primarily a disorganization of though independent of current definitions of the positive/negative symptom construct. A second cluster of symptoms (affective flattening, avolition/apathy, and anhedonia) appeared to reflect predominantly blunting of affect and volition. A third cluster (delusions, hallucinations, and "breadth of psychosis") seemed to represent only the florid psychotic features. The first and (to a lesser extent) second clusters of symptoms were selectively associated with neuropsychological impairment. The patterns of neuropsychological deficits correlated with the first cluster of symptoms appeared to be consistent with a process characterized by failure in the development of a normal repertoire of cognitive abilities. It is suggested that the "defect state" may not be a monothetic construct, and that within the domain of "type II" schizophrenia, disturbances of thought may be distinguished from those of affect and motivation. PMID- 4035305 TI - Multiple contributions to clinical presentation of flat affect in schizophrenia. AB - Flat affect has long been recognized as a central manifestation of schizophrenia, and has more recently been appreciated as a stable and prognostically important attribute of this disorder. Yet, because it is thought to be difficult to evaluate, flat affect has been deemphasized in criterion-based diagnostic systems. Results of this study suggest that the clinical evaluation of flat affect may be contaminated by a number of behaviorally similar processes. The components we identified included right hemisphere dysfunction, retardation and extrapyramidal effects, as well as the sequelae of hospitalization. Thus, in the clinical evaluation of flat affect, a multivariate approach in which these different components are considered separately might improve the reliability of evaluation and make this important sign more useful. PMID- 4035306 TI - Negative symptoms in schizophrenia: their longitudinal course and prognostic importance. AB - Negative and positive symptoms were investigated longitudinally in 39 young schizophrenic patients at two followup assessments approximately 2.5 and 5 years after hospital discharge. Negative symptoms, such as flat affect and poverty of speech, which were assessed at the first followup, were found to be effective prognostic signs in schizophrenic patients for predicting later poor role functioning at the second followup. The prognostic importance of negative symptoms was predominantly due to their tendency to occur in patients who were already functioning poorly in social and instrumental areas at the first followup, and who tended to continue doing poorly at the second followup. Contrary to some current hypotheses, positive symptoms, such as delusions and hallucinations, were also found to be prognostic of later deficits in role functioning at the second followup. Negative symptoms appeared to be generally persistent over time, although there was some tendency toward remission. Potential models of the etiology of negative symptoms and their role in schizophrenia are proposed. PMID- 4035307 TI - Negative symptoms: future developments of the concept. AB - The concept of negative symptoms has become increasingly important since it was reintroduced into psychiatric thinking several years ago. As the possible significance of negative symptoms has become clarified, the complexity of this concept has also become apparent. In dealing with this complexity, major progress has been made in describing negative symptoms more reliably and in taking steps toward identifying possible biological correlates. But two other particularly important directions also need to be pursued. First, psychosocial factors need to be explored further both in terms of their etiological contributions to negative symptoms and in the way these symptoms influence psychosocial aspects of the evolution of disorder and recovery. Secondly, more attention must be focused on the potential that negative symptoms have for providing an understanding of the interface between biological, psychological, and social processes in psychiatric disorder. In these ways the study of negative symptoms may contribute major clues to the nature of psychopathology, its etiologies, and its course. PMID- 4035308 TI - Negative symptoms: are they indigenous to schizophrenia? AB - The sudden popularity of positive and negative symptoms (PNS) has probably arisen as a result of the need for an instrument for clustering schizophrenic patients into subgroups that would respond similarly to the various treatments. The relation of PNS to the three major models for the etiology of schizophrenia (disease, socioenvironmental, and vulnerability) has been delineated. The question was raised regarding the indigenous nature of negative symptoms, their permanency, and whether they can be used to test the tenability of the three models. A strategy was suggested for determining whether the negative symptoms are permanent features of schizophrenia by providing techniques for attempting to eliminate them through therapeutic intervention. The need for developing operational criteria for the presence of each symptom was suggested to improve reliability of ratings, and construct validity designs were formulated for increasing their validity. The provision of a valid and reliable scale for negative symptoms and a scientific model for encompassing the various claims for negative symptoms is necessary before progress can be made. PMID- 4035309 TI - First person account: "freedom" means knowing you have a choice. AB - The following essay is my contribution to the First Person Accounts section of the Schizophrenia Bulletin. After a description of the development of my schizophrenic illness, I briefly address the issues of treatment noncompliance, institutionalization, and how they have affected my life. The main focus of my article is on personal control over the illness and on recognizing when medication is necessary. I give a personal example of how I have controlled some minor symptoms without medication, with the understanding that when symptoms become too disruptive, medication is helpful and certainly indicated. PMID- 4035310 TI - Chemical water and wastewater treatment. Practical experience and new concepts. Proceedings from the 1st Gothenburg Symposium, 1984. PMID- 4035311 TI - [Human ecology. Public health aspects of the environment, interiors and developments]. PMID- 4035312 TI - [Introduction to environmental health from the viewpoint of relevance to humans]. PMID- 4035313 TI - [International comparison of strategies for assurance of the quality of indoor air]. PMID- 4035314 TI - [Indoor climate components--significance and measurement]. PMID- 4035315 TI - [Appropriate formulation and application of air-polluting and other pest control agents. Experimental experiences within the framework of tests based on Paragraph 10 c of the Federal Communicable Disease Law]. PMID- 4035316 TI - [Radioactive materials in the environment--the need for minimizing their presence and standards for their limitation]. PMID- 4035317 TI - Reproductive and developmental toxicity of metals. AB - This paper discusses metal exposure in the male, the nonpregnant female, and the maternal-offspring unit. In the first two situations, the primary targets are the gonads. In the mother-offspring unit, consideration must be given to effects on the fertilized ovum, the growth of the embryo, and, finally, to the fetal and perinatal stages. The central nervous system may be especially vulnerable during development. The placenta also undergoes development, and either the placenta or the fetus may be the primary target. In humans, certain metals may cause abortion or other effects on the conceptus. Effects may also be produced by metal exposure both in utero and in the suckling infant. For example, methylmercury gives rise to a range of effects on the central nervous system at doses lower than those producing damage to the mature nervous system. Effects of lead and arsenic are associated mainly with postnatal exposures during infancy and early childhood, but there is reason to believe from animal experiments that some effects may occur from prenatal exposures to certain metal compounds. PMID- 4035318 TI - [Biological monitoring of exposure to industrial toxic substances. Present-day situation and prospects for development]. AB - Biological monitoring of exposure to an industrial chemical may be defined as the evaluation of the internal dose (internal exposure) by a biological method with the view of assessing the associated health risk. Depending on the biological parameter selected and on the time of sampling, internal dose may mean the amount of chemical recently absorbed, the amount stored in one or several compartments of the organism, or, under ideal conditions, the amount bound to the sites of action. The estimation of the internal dose has usually relied on two categories of tests: those based on the determination of the chemical and/or its metabolites in various biological media (eg, alveolar air, blood, urine) and those based on the quantification of a nonadverse biological effect, the intensity of which is related to the internal dose. Biological tests providing information on the amount of active chemical bound to the critical sites of action (target dose) and noninvasive analytical methods which measure the amount of cumulative toxins stored in certain body compartments (eg, bone, liver, kidney) are currently being developed. The main criteria to be considered in the selection of the most appropriate biological monitoring test of exposure are the specificity of the parameter and its sensitivity with respect to the exposure level, the analytical and biological applicability, the convenience for the workers, the possible risks associated with its application, and, of course, the accuracy of the exposure and/or health risk evaluation. Normally, the biological approach of exposure monitoring is reserved for chemicals which enter the organism and may exert systemic toxic effects. When a biological monitoring test of exposure is applicable, it offers several advantages over ambient air monitoring. A biological parameter reflecting the internal dose is necessarily more closely related to the systemic adverse effect(s) than any environmental measurement. Biological monitoring of exposure integrates the exposure by all routes (pulmonary, oral, and cutaneous) and sources. It may also take into account several factors which determine the uptake and the absorption of the chemical (individual variability, work load, hygiene habits, etc). However, contrary to ambient monitoring, biological monitoring is applicable only when sufficient information has been gathered on the metabolism of the chemical, its toxicity or that of its metabolites, and when some of the relationships between external exposure, internal dose and adverse effects have been assessed.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 4035319 TI - Strategies of air sampling. AB - Considerations relevant to preparation for air sampling are reviewed, including purpose, recognition of need, and the logistics of obtaining the samples (where, when, how, and for how long). Three strategies of sampling focused on how many samples to obtain are discussed in detail, ie, the zoning strategy and strategies of the National Institute for Occupational Safety and Health (NIOSH) and the Mining Safety and Health Administration (MSHA). The purpose of the zoning method is to locate groups of employees with high exposures, while the NIOSH method aims at determining compliance of individual sample results with a regulatory standard. Similarities and differences between the methods are highlighted. The MSHA strategy is completely regulatory and represents a scientifically indefensible strategy. Finally, the advantages of incorporating the assumption of a distribution of workplace contaminant-in-air concentrations are noted. PMID- 4035320 TI - Occupational cancer. Where now and where next? AB - For each kind of occupationally associated cancer, there are three distinct stages in the development of the problem: recognition of a possible problem, confirmation, and the introduction of preventive measures. In the past, recognition of a possible problem depended heavily on chance and on the powers and observation of dedicated physicians and surgeons. Confirmation consisted of the collection of further anecdotal evidence and the conduct of case-referent (case-control) or other studies. The introduction of preventive measures often lagged woefully behind confirmation that a problem existed. Recently, the power of epidemiology as a primary investigative tool has grown to the point where unsuspected associations between occupation and cancer risk may be the first hint that a problem exists. However, it is important to recognize that investigative epidemiology is capable of constructing misleading pictures. In the future there is bound to be continuing pressure to reduce maximal permissible exposure to proven carcinogens. For chemicals for which there is no more than suspicion based on laboratory tests, one must ensure that regulatory action is based on good science, sound judgement, and common sense, rather than on the machinations of those with vested interests, of ambitious lawyers, or of the lunatic fringe. Less than 10% of all cancers are likely to be due to occupational factors. Therefore, even turning the world upside down with safety precautions against actual and suspected carcinogens would only marginally affect the present human cancer burden. PMID- 4035321 TI - Pesticides. AB - The last 30 years have been marked by concern regarding the effects of pesticides on human health and on the environment. Unwanted and adverse effects on man and other nontarget organisms have been reported from many countries. The health effects recorded for thousands of people yearly are mainly caused by the inappropriate handling of pesticides or by accidents. The important task is to identify and evaluate the specific hazards of the handling and application of pesticides and the need to collaborate with the World Health Organization (WHO) and other organizations on promoting the health protection of exposed workers. The selectivity of chemical control methods can often be markedly improved by the proper choice of formulation and application techniques and, of course, by an appropriate choice and use of the pesticide itself. This work is an integral part of the international program on chemical safety based on and incorporating current WHO activities. The situation in the developing countries creates a new dimension for the work to be done. In these countries the working populations are affected by the general diseases prevailing in the community, as well as by many uncontrolled hazardous agents at work. PMID- 4035322 TI - Organic dusts and lung reactions--exposure characteristics and mechanisms for disease. AB - Exposure to organic dusts has been related to pulmonary occupational diseases in a variety of environments. These dusts contain several different agents, but the microbial contamination is always important, particularly regarding molds and Gram-negative bacteria. In the lung, organic dusts cause a series of reactions ranging from irritation with neutrophilic invasion to the initiation of cell mediator release and the development of antibodies. For certain diseases, such as byssinosis, the relation between the cell reactions and the disease is relatively well established; for others, such as allergic alveolitis (hypersensitivity pneumonitis) with fibrosis, more research is needed before the pathogenesis can be established. An understanding of the specific agents causing the disease and the cellular reactions behind its development is essential for its prevention. PMID- 4035323 TI - The case-referent study--some comments on its structure, merits and limitations. AB - Case-referent (case-control) studies have become increasingly important in occupational health epidemiology. The concept of study base [Miettinen, Scand J Work Environ Health 8 (1982):suppl 1, 7-14] as referring to the health experience of the study population over time, and a clear recognition of open and closed populations, ie, with or without turnover, make the structure of the case referent study clearer. The referents should represent the study base in terms of exposure and nonexposure and even with regard to other determinants of the disease under study. Case-referent studies refer to open populations unless nested in cohorts. Matching in cohort studies is straight-forward and creates a symmetrical situation among the exposed and unexposed with regard to the matching factor, but this symmetry is not achieved in case-referent studies, in which matching tends to distort the representativeness of the referents with regard to the study base. This circumstance suggests that matching on determinants of the disease should be maintained in the analysis. However, since the referents are a sample of the base, there might be confounding in the data, which does not exist in the base and vice versa, ie, full control of confounding in case-referent studies is not achievable either through matching or through any other procedure, but a large sample of referents would more properly reflect the distribution of confounders in the base. Using hospital referents, one has to consider possible relations between the referent diseases and the exposure under study, and therefore evaluation of multiple exposures may even require different sets of hospital referents.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4035324 TI - Man-made mineral fibers and health. Answered and unanswered questions. AB - An overall assessment of the epidemiologic evidence from 23 published studies on workers' health in the industry producing man made mineral fibers (MMMF) (21 studies) and in the user industry (2 studies) is presented. Three major studies recently published, one cross-sectional and two of the historical cohort type, conducted in the producer industry, have been singled out for closer examination and discussion. The combined evidence from the epidemiologic studies indicates that causal associations between MMMF occupational exposure, as it occurred in past decades, and lung cancer and chronic respiratory diseases cannot be excluded, neither does it offer clear support for such associations. Experimental data indicate clearly that a fibrogenic effect can be obtained by the intratracheal administration of MMMF and a carcinogenic effect by the intratracheal, intrapleural, and intraperitoneal administration of MMMF, while no appreciably fibrogenic nor carcinogenic effects have been detected in inhalation experiments. While it can be stated that no long-term pathological effects have been observed in MMMF workers in the first 20 years or so after first employment, the key scientific issue of whether MMMF are fibrogenic and/or carcinogenic in man when inhaled remains still open. PMID- 4035325 TI - Current problems of nonionizing radiation. AB - Electromagnetic radiation in the radiofrequency range is the most common type of nonionizing radiation. The accelerated development in telecommunications and the introduction of power transmission lines, as well as glue drying and plastic heating in the wood and plastic industries, cause both occupational and nonoccupational systematic exposure to electromagnetic radiation in the radiofrequency range. For the hygienic rating of radiowave exposure it is necessary to use biological models to evaluate, in depth, the mechanisms and effects of electromagnetic radiation. The ultra- and superhigh frequency range is the most active in causing biological responses. The high frequency range is less active. Physical characteristics (continuous and impulse) and the combined effect of the electromagnetic field with other factors, eg, elevated air temperature, etc, have an effect on biological responses. PMID- 4035326 TI - 1984 and occupational health in developing countries. AB - The developing countries constitute a large and important sector of the world. Their needs and aspirations require serious consideration by the international scientific community. When considering the countries of the developing world, it must be appreciated that they do not constitute a homogeneous entity but are a disparate group with different cultural backgrounds and at varying stages of economic and industrial development. But in spite of such diversity, it is possible to establish at least two issues of common interest to these nations. The first is in relation to the setting of environmental standards in the workplace. In the setting of such standards cultural, political, social, economic, and administrative factors must be taken into consideration. In some situations, for economic reasons, the standards may have to be less stringent than the prevailing standards in the industrialized world. On the other hand, because of administrative and health reasons, they may have to be more stringent. Finally, the issue of scientific research relevant to developing countries is considered in the paper. PMID- 4035327 TI - [Occupational medicine for small business. Realizations and perspectives]. AB - Occupational health for small enterprises includes more problems than rewards: scattered workforce, limited financial means, wide differences in sociological and technological status, few manifest results, etc. But it is probably the most necessary application of the concept, although it is generally less compulsory. What is to be recommended now? One must keep in mind that small workplaces have a special need for occupational health care (even if they fail to recognize it). Tactical priorities must be ranked according to needs and means. Incentives and regulations that are not too encroaching should be set. Occupational health units should be comprised of complementary technicians. Specific research with technical and sociological expertise should be implemented. Changes in conditions should not be made merely for change alone, but after careful evaluation and without passivity. The feeling of being health's missionary in the Kingdom of production should be retained. PMID- 4035329 TI - [Pathology of gastric mucosa polyps]. AB - More frequent use of the endoscope to remove gastric mucosal polyps has also led to better knowledge of the pathology of these polyps. Their classification is still a matter of debate, and hence, by way of introduction, the notions of hyperplastic, hyperplasiogenous and hyperplastic-adenomatous polyp, adenoma, borderline lesion protruded type, foveolar hyperplasia and cysts of the gastric glands are presented. The authors give preference to the WHO classification of 1977. Among 196 mucosal polyps examined between 1970 and 1982 84% were hyperplastic (hyperplasiogenous) polyps, 15.5% adenomas and there was a single specimen of hamartomatous polyp. One in every 6 adenomas showed malignant changes and 5 of the 165 hyperplastic polyps were associated with gastric carcinoma. Problems of diagnosis, classification and prognosis are briefly discussed. PMID- 4035328 TI - [Modification of serum lipids, lipoproteins and apoproteins AI and B in patients with hyperlipidemia Type IIa and IIb using polyenylphosphatidylcholine]. AB - In a double blind study 27 patients with type II hyperlipidemia (8 IIa and 19 IIb) were treated as follows: 13 received placebo and 14 sn polyenylphosphatidylcholin (PPC) (P 0206/1/01, Nattermann GmbH, Cologne) in a dose of three times 450 mg b.i.d. In all patients, and also in the two subclasses of patients with type IIa and type IIb hyperlipidemia, total cholesterol and LDL cholesterol were lowered significantly by PPC. The other parameters showed only minor variation. There was a downward trend in apoprotein B, triglycerides and VLDL cholesterol, and an upward trend in apoprotein AI, with virtually unchanged HDL cholesterol. None of these variations was significant compared with placebo. The fall in LDL cholesterol with unchanged HDL cholesterol caused a statistically significant decrease in the LDL cholesterol/HDL cholesterol ratio, thus supporting the hypothesis of an antiatherogenic property of PPC, as demonstrated experimentally in various animals. PMID- 4035330 TI - [The use of low-dose amitriptyline in psychogeriatrics. A clinical, pharmacokinetic and pharmacogenetic study]. AB - Two groups of six depressive psychogeriatric patients (age 69-93) have been treated for three weeks with either 25 mg or 50 mg of amitriptyline (AT) per day. Before the beginning of the treatment and after 8, 15 and 22 days of medication, the patients (7 outpatients and 5 hospitalized patients) underwent various psychopathological tests (Hamilton, Crichton) and biochemical investigations, i.e. clinical chemistry and hematology, analyses of AT and nortriptyline (NT), in the plasma. In some subjects the hydroxylated metabolites and the binding of these substances to plasma proteins were also measured. Except one patient, all responded favourably to the treatment. No difference between the two doses has been observed as regards their clinical efficacy and incidence of side effects. The plasma levels of AT and NT were below those generally recommended in the literature. The monitoring served to identify some cases of noncompliance and, in one patient, a deficiency of hydroxylation of AT, confirmed by the debrisoquine test. These results suggest that the "therapeutic window" needs redefinition and that low-dose medication with antidepressants is indicated in a psychogeriatric population. PMID- 4035331 TI - [Self-monitoring of airway obstruction using the peak flowmeter]. AB - Daily peak flow measurements provide an accurate and objective assessment of airway obstruction. The peak flow profile offers a rational basis for antiobstructive treatment. Success and failure of treatment are visualized, as are the asymptomatic beginning of an asthmatic attack, an allergen exposure or an exercise-induced obstruction. Compliance improves, and self-monitoring seems to increase patient comfort. A considerable amount of knowledge about the dynamics of airway obstruction is conveyed to the physician, and this works very much to the benefit of his patient. PMID- 4035332 TI - [Accidents in general anesthesia in cats and dogs. 1]. PMID- 4035333 TI - [Coccidiosis in sheep]. PMID- 4035334 TI - [Field studies of selenium status and placental retention in cattle]. PMID- 4035335 TI - [Maximal aerobic capacity ans anaerobic threshold in 16-km runners]. PMID- 4035336 TI - [Effect of a carbohydrate diet on the physical fitness and metabolism regulation in highly trained marathon runners]. PMID- 4035337 TI - [Echocardiography of endurance athletes as a function of VO2 max]. PMID- 4035338 TI - [Value and significance of serum myoglobin in sportsmen before and after various physical activities]. PMID- 4035339 TI - [Sport-Tester PE 3000 training system]. PMID- 4035340 TI - Aluminum: is it toxic to the human brain? PMID- 4035341 TI - The combined effect of tobacco and alcohol consumption on the level of lead and cadmium in blood. AB - This study deals with the person-to-person variation in the levels of lead and cadmium in the blood of 6437 subjects (2883 men and 3554 women). The lead level (Pb-B) is clearly higher in men than in women, and the cadmium level (Cd-B) is a little higher in men than in women. Only the Pb-B varies according to age for both sexes. The results reveal that the consumption of alcohol could play an important part in the variation of lead and cadmium levels in the blood; the consumption of alcohol is associated with an increase in Pb-B but a decrease in Cd-B. These variations involving alcohol consumption remain significant regardless of smoking habits. On the other hand, an increase in Pb-B and Cd-B has been noted among smokers and, to a lesser degree, among former smokers, compared with non-smokers. PMID- 4035342 TI - Lead in water, infant diet and blood: the Glasgow Duplicate Diet Study. AB - The Glasgow Duplicate Diet Study was carried out to investigate the effect of lead in drinking water on the blood-lead of infants. A stratified group of 131 mothers and babies were followed from antenatal registration until the children were 3 months of age. The infants' dietary intakes of lead were assessed by composite water sampling and by the "duplicate diet" technique. Blood-leads were measured from venous samples. Statistical analysis in this paper covers sampling variability, the dependence of diet-lead on water-lead, the relationship of blood lead in the baby's cord to that in the mother, and the contribution of water-lead to the blood-lead (at 13 weeks) of infants that were bottle-fed. The variation associated with sampling for lead in water was taken into account when estimating the relationship between water-lead and blood-lead and when discussing how standards for their respective concentrations should be linked. The conclusion is consistent with an upper guide value of 0.05 mgl-1 for the concentration of lead in drinking water. PMID- 4035343 TI - Medicinal plants. PMID- 4035345 TI - The generative grammar of the immune system. PMID- 4035344 TI - Defining lipid transport pathways in animal cells. AB - A new technique for studying the metabolism and intracellular transport of lipid molecules in living cells based on the use of fluorescent lipid analogs is described. The cellular processing of various intermediates (phosphatidic acid and ceramide) and end products (phosphatidylcholine and phosphatidylethanolamine) in lipid biosynthesis is reviewed and a working model for compartmentalization during lipid biosynthesis is presented. PMID- 4035346 TI - "Right-to-life" scores new victory at AID. PMID- 4035347 TI - Contraception research lagging. PMID- 4035348 TI - Guilty plea puts Oraflex case to rest. PMID- 4035349 TI - Attractive forces between uncharged hydrophobic surfaces: direct measurements in aqueous solution. AB - Long, double-chained alkylammonium acetate surfactants are soluble in water and, under suitable conditions, adsorb onto sheets of muscovite mica, forming an electrically neutral, hydrophobic surface. Attractive forces measured between such surfaces are 10 to 100 times stronger than expected from van der Waals theory over distances D up to about 10 nanometers. The forces decay exponentially [with a force proportional to exp(-D/1.4)] instead of following the power-law behavior of continuum theory. The results of these and earlier experiments indicate that the strength of these attractive forces depends critically on the degree of hydrophobicity of the surface and is due to the long-range influence of the surface on the structure of water. In addition, for very hydrophobic surfaces, the cavitation effects on pulling the surfaces apart are described. PMID- 4035350 TI - Enhanced metabolism of Leishmania donovani amastigotes at acid pH: an adaptation for intracellular growth. AB - Amastigotes (tissue forms) of Leishmania donovani isolated from infected hamster spleens carried out several physiological activities (respiration, catabolism of energy substrates, and incorporation of precursors into macromolecules) optimally at pH 4.0 to 5.5. All metabolic activities that were examined decreased sharply above the optimal pH. Promastigotes (culture forms), on the other hand, carried out the same metabolic activities optimally at or near neutral pH. This adaptation to an acid environment may account in part for the unusual ability of amastigotes to survive and multiply within the acidic environment of the phagolysosomes in vivo. PMID- 4035351 TI - Responsiveness and receptive field size of carp horizontal cells are reduced by prolonged darkness and dopamine. AB - In the fish retina the interplexiform cells contain dopamine and provide a centrifugal pathway from the inner plexiform layer to horizontal cells of the outer plexiform layer. Dopamine application reduced the responsiveness and receptive field size of cone horizontal cells, as did a prolonged period of complete darkness. Other results suggest that the interplexiform cells may release dopamine after a prolonged period in the dark. The interplexiform horizontal cell system may modify the strength of the antagonistic surrounds of retinal neurons as a function of time in the dark. PMID- 4035352 TI - Crystallographic structure of the octamer histone core of the nucleosome. PMID- 4035353 TI - Basic modular format in tRNA's and rRNA's. PMID- 4035354 TI - Superinduction of c-fos by nerve growth factor in the presence of peripherally active benzodiazepines. AB - Alterations in proto-oncogene expression after stimulation of rat pheochromocytoma (PC12) cells by nerve growth factor (NGF) have been investigated. A specific stimulation of c-fos messenger RNA and protein was detected 30 minutes after treatment. This induction was enhanced more than 100 fold in the presence of peripherally active benzodiazepines. The effect was specific as very little change was observed in the levels of c-rasHa, c-rasKi, c myc, and N-myc messenger RNA's. Under the conditions used here, NGF treatment ultimately results in neurite outgrowth, with a reduction or cessation of cell division. Thus, stimulation of the c-fos gene in this system appeared to be associated with differentiation and not with cellular proliferation. The effect of benzodiazepines was stereospecific and represents a novel action of these compounds at the level of gene expression. PMID- 4035355 TI - Migration and differentiation of cerebral cortical neurons after transplantation into the brains of ferrets. AB - Cells from the cerebral proliferative zones of newborn ferrets were labeled with tritiated thymidine and a fluorescent dye and were transplanted as a single-cell suspension into the occipital region of newborn ferrets. The transplanted cells became thoroughly integrated into the host environment: many cells migrated through the intermediate zone and into the cortical plate, where they developed as pyramidal neurons. Other transplanted cells came to resemble glial cells. After 1 to 2 months most transplanted neurons had taken up residence in layer 2 + 3, the normal destination of neurons generated on postnatal days 1 and 2. Thus the sequence of morphological differentiation and the eventual laminar position of the isochronically transplanted neurons closely paralleled that of their normal host counterparts. PMID- 4035356 TI - Glucocorticoids potentiate ischemic injury to neurons: therapeutic implications. AB - Sustained exposure to glucocorticoids, the adrenocortical stress hormones, is toxic to neurons, and such toxicity appears to play a role in neuron loss during aging. Previous work has shown that glucocorticoids compromise the capacity of neurons to survive a variety of metabolic insults. This report extends those observations by showing that ischemic injury to neurons in rat brain is also potentiated by exposure to high physiological titers of glucocorticoids and is attenuated by adrenalectomy. The synergy between ischemic and glucocorticoid brain injury was seen even when glucocorticoid levels were manipulated after the ischemic insult. Pharmacological interventions that diminish the adrenocortical stress response may improve neurological outcome from stroke or cardiac arrest. PMID- 4035357 TI - Deficient vasoactive intestinal peptide innervation in the sweat glands of cystic fibrosis patients. AB - The innervation of acini and ducts of eccrine sweat glands by immunoreactive, vasoactive intestinal peptide-containing nerve fibers was sharply reduced in seven patients with cystic fibrosis compared to eight normal subjects. The decrease in innervation by this neuropeptide, which has been shown to promote blood flow and the movement of water and chloride across epithelial surfaces in other systems, may be a basic mechanism for the decreased water content and relative impermeability of the epithelium to chloride and other ions that characterize cystic fibrosis. PMID- 4035358 TI - Spinal reflexes in microgravity: measuring H reflexes during space flight. PMID- 4035359 TI - Z-DNA forms without an alternating purine-pyrimidine sequence in solution. AB - Nuclear magnetic resonance spectra (proton and phosphorus-31) and ultraviolet absorption spectra of the DNA decamer d(br5CGbr5CGATbr5CGbr5CG), in which the central two adenine-thymine base pairs are out of order with the rest of the purine-pyrimidine alternation sequence, indicate that under appropriate solvent conditions (high salt and methanol) the molecule undergoes a structural transition from a right-handed B-DNA conformation to a left-handed Z-DNA conformation. Measurements of the two-dimensional nuclear Overhauser effect on the decamer indicate that all of the guanines as well as the two equivalent thymines adopt the syn conformation. PMID- 4035360 TI - The 23-million-dollar quest pays off. PMID- 4035361 TI - Amidolytic antifactor Xa assays in the laboratory evaluation of heparin and low molecular weight fractions. PMID- 4035362 TI - Practical considerations on the measurement of low molecular weight heparin anti Xa activity. PMID- 4035363 TI - Usefulness of fibrinopeptide A generation tests in experimental and clinical studies with low molecular weight heparin fractions. AB - FPA generation test provides a sensitive tool to study the events leading to the production of fibrin from fibrinogen. Drug modulation of pathways resulting in thrombin generation can be readily assessed utilizing the FPA generation test. In circumstances in which conventional clotting and amidolytic methods fail to detect any antiprotease effects, the FPA generation test provides the sensitivity to study these actions. The FPA generation test demonstrates the collective action of antithrombotic agents on inhibition of activation of the pathways leading to the generation of thrombin. The generation systems are easily modified by activators to provide identification of sites, components, and modulating interaction of various heparin derivatives on the hemostatic system. The FPA generation test assesses the overall inhibitory effects of heparin and thus provides insight into the pharmacokinetics of the biologically active components of these agents. Currently, the FPA generation test may be utilized to demonstrate pharmacokinetics and pharmacodynamics but has limited quantitative capacity in this regard. The FPA generation test performed on native plasma may provide insight into the great variation in individual hemostatic parameters important to dosage determinations. PMID- 4035364 TI - A primate model (Macaca mulatta) to study the pharmacokinetics of heparin and its fractions. AB - We have extensively studied the hemostatic parameters and the responses to the anticoagulant action of heparin and its fractions in the primate model (M. mulatta) and found these to be identical to those obtained in humans. The functional properties of antithrombin III, alpha 2-antiplasmin, and platelet factor 4 were also identical to humans in amidolytic and coagulant assays. Human antibodies against FPA, B beta 15-42 peptide, platelet factor 4, and thromboxane B2 reacted with the primate antigen, and assays were developed to measure these parameters in primates. Infusion of activated prothrombin complex concentrates (more than 100 U/kg/day) on a continual basis up to 3 days resulted in a hypercoagulable state manifested by an elevation of FPA, thromboxane B2, and changes in the thrombelastographic patterns. Similarly, infusion of homologous primate serum also resulted in a hypercoagulable state, as was evident by a sharp increase in the FPA levels. The antithrombotic effects of intravenous and subcutaneous administration of heparin, its low molecular fraction, and their constituents were studied after intravenous and subcutaneous injections. The low molecular weight fractions showed the most effective antithrombotic effects, whereas somewhat milder protection was observed with the starting material and highly anionic fraction. The prolongation of global tests, such as the APTT, TT, and changes in the thromboelastogram did not correlate with the reduction in the blood markers of hypercoagulable state. A modified simplate bleeding time method was used to study the effect of heparin and its fractions on the bleeding profile of heparin fractions. The components of fibrinolytic systems were also measurable in both the clot-based and amidolytic methods to predict the profibrinolytic actions of heparin fractions in its mode. These studies suggest that plasma markers, such as the platelet release proteins, products of thrombin activation, and prostaglandin metabolites, may provide better indices in the monitoring of the antithrombotic actions of newer heparins and antithrombotic drugs. Studies suggest that the pathophysiologic responses after a thrombogenic trigger in the primate model are close to humans, and drug modulation of these may provide relevant clinical information. This model provides the most similar preclinical model to study the actions of heparin fractions. PMID- 4035365 TI - Biochemical and pharmacologic studies on the protamine interactions with heparin, its fractions and fragments. PMID- 4035367 TI - Heparin and its derivatives. Part two: Applied aspects and future considerations. PMID- 4035366 TI - An objective assessment of the interaction of heparin and its fractions with human platelets. AB - We have shown that heparin and heparin fractions cause in vitro platelet aggregation in a large portion of a normal population. Furthermore, this aggregation occurs in a concentration-dependent manner and is not related to the anti-Xa activity of heparin or its fractions. In addition, it appears that at least part of the mechanism by which heparin induces aggregation is through the production of thromboxane. However, this is not the sole mechanism, since approximately 20% aggregation still occurs when thromboxane production is totally inhibited or the thromboxane receptor is completely blocked. Furthermore, although protamine (at the concentrations used) completely neutralizes the anticoagulant activity of heparin, it does not always completely inhibit the platelet aggregating activity of heparin. Finally, we have shown that heparin alone promotes thromboxane production and PF4 release in a whole blood system. Additional studies are needed to characterize further the mechanisms of heparin induced platelet aggregation. PMID- 4035368 TI - Biologic studies on chemically synthesized pentasaccharide and tetrasaccharide fragments. AB - We have synthesized the pentasaccharide representing the binding site of heparin to AT III. This pentasaccharide contains a 3-0-sulfate group on one of its glucosamine units. A pentasaccharide analogue lacking this 3-0-sulfate group and two different tetrasaccharides, each being part of the pentasaccharide sequence with AT III affinity, have also been synthesized. The pentasaccharide with high affinity for AT III also shows high antifactor Xa activity and, in vivo, antithrombotic activity. Removal of glucosamine at the nonreducing end maintains partial binding capacity as well as partial antifactor Xa activity. PMID- 4035369 TI - Oligosaccharides formed by treatment of heparin with nitrous acid. PMID- 4035370 TI - Preliminary biochemical and pharmacologic studies on a chemically synthesized pentasaccharide. PMID- 4035371 TI - Quinidine induced lupus syndrome. AB - Five patients with a lupus-like syndrome secondary to quinidine are described. Eleven other cases have previously been reported. The quinidine induced lupus syndrome is similar to that seen with procainamide and hydralazine treatment but occurs less frequently. The lower incidence may reflect a difference in the metabolism of quinidine. Quinidine should be considered as potentially responsible when multisystem disease appears in patients receiving this drug. PMID- 4035372 TI - [A new nail profile for an interlocking nail with high fatigue stability]. PMID- 4035373 TI - [Closing of an old post-traumatic diaphragmatic defect using homologous material under the circumstances of a second trauma]. PMID- 4035374 TI - [Conservative versus surgical therapy of abduction fractures of the femur neck. Results of a clinical follow-up]. PMID- 4035375 TI - [Separation of the distal femoral epiphysis]. PMID- 4035376 TI - [Healing of reimplanted osteochondral fragments. An experimental study]. PMID- 4035377 TI - [Ambulatory surgery of ruptured collateral ligaments of the fibulotalar joint]. PMID- 4035378 TI - [Histomorphology following plate osteosynthesis in the human. I: Fracture behavior, microfissures and reposition]. PMID- 4035379 TI - [Histomorphology following plate osteosynthesis in the human. II: Cortical plate screws and compression screws]. PMID- 4035380 TI - [Ender nailing with expanded indications]. PMID- 4035381 TI - Critical review of 153 operatively treated closed tibial shaft fractures. PMID- 4035382 TI - Mismanagement of acute hematogenous osteomyelitis by traditional medicine men (native doctors) in the eastern and northern regions of Nigeria. PMID- 4035383 TI - [Roentgen-negative retractors in osteosyntheses of the spine]. PMID- 4035384 TI - [Compression effect of the dynamic hip screw. Experimental study on cadaveric bone]. PMID- 4035385 TI - Radionuclide studies of the spleen in trauma and iatrogenic disorders. AB - The first task of radiocolloid spleen imaging, after trauma, is to determine if the organ is functioning. If this cannot be demonstrated, splenic avulsion must be considered. The second task is to document splenic injury (not to suggest splenectomy, but to serve as a baseline for following later healing). Failure to heal may be a risk factor for subsequent splenic rupture. The third task of spleen imaging is to determine if accessory splenic fragments are present and functional. The radiocolloid spleen scan facilitates the successful accomplishment of all of these tasks. PMID- 4035386 TI - In utero diagnosis and treatment of fetal supraventricular tachycardia. PMID- 4035387 TI - Ethical considerations in and beyond experimental fetal therapy. PMID- 4035388 TI - Legal issues in fetal therapy. PMID- 4035389 TI - Prenatal treatment of biochemical disorders. PMID- 4035391 TI - Gamut. Cardiac and great vessel calcifications in childhood. PMID- 4035390 TI - Ventriculomegaly: evaluation and management. PMID- 4035393 TI - Convocation address delivered on 18th Nov 1984 to medical, dental and law graduates. PMID- 4035392 TI - Case of the season. Inflammatory fibrous polyp of esophagus. PMID- 4035394 TI - Self-medication in Singapore. PMID- 4035395 TI - Anaesthetic management for the excision of carotid body tumours--a report of two cases. PMID- 4035397 TI - Some aspects of sexual knowledge and sexual behaviour of local women. Results of a survey. V. Sexual intercourse. PMID- 4035396 TI - The use of the HYPOCOUNT IIB in the diagnosis of hypoglycaemia in neonates. PMID- 4035398 TI - Parasuicides in Kuala Lumpur. A descriptive study. PMID- 4035399 TI - A five-year follow-up study of schizophrenia in Singapore. PMID- 4035400 TI - Correction of bimaxillary deformity--a surgical dilemma? Preliminary report of eight cases. PMID- 4035401 TI - The restoration of body weight in anorexia nervosa through operant conditioning: a case report. PMID- 4035402 TI - Midtrimester termination of pregnancy using intravaginal gemeprost (16, 16 dimethyl-trans delta 2 PGE1 methyl ester, cervagem). PMID- 4035404 TI - Health and social science in Latin America. PMID- 4035403 TI - Polytherapy in multibacillary leprosy patients in Nepal. PMID- 4035405 TI - Assessment of Venezuelan health services from a social development perspective. AB - This paper evaluates four health programs housed in the Venezuelan Ministry of Health and Social Assistance: malaria eradication, infant paralysis, highrisk pregnancy and child birth and community participation. For each of the programs the study (a) identifies key management features relating to structure and strategy; (b) examines program performance to assess its consistency with the declared objective of promoting social development; and (c) evaluates what structure and strategy features may have contributed to the social development of the target community. Also, the information mechanisms which link planners, executors and the 'clients', were examined. Lastly, the extent to which target population involved in the decisions made with respect to each program, was reviewed. PMID- 4035406 TI - Studies of diarrhoea in Quindio (Colombia): problems related to water treatment. AB - This paper studies the association between fluctuations in rates of diarrhoea among children less than 5 years old in Armenia (Quindio) and variations in the application of chlorine in the aqueduct of the city. The study shows that to a great extent diarrhoea morbidity can be explained by the application of chlorine which does not reach useful levels of concentration during the required time. The article concluded by recommending the improvement of existing treatment plants and investing the necessary resources in new plants to insure the quality of water. PMID- 4035407 TI - Ideological dimensions of community participation in Latin American health programs. AB - A comparative analysis of community participation in urban and agricultural programs, and health programs in Latin America suggests that the promotion of community participation was based in all cases on two false assumptions: the belief that the traditional values of the poor were the main obstacle for development and for health improvement; and the idea that the poor were incapable of organizing themselves. A country by country examination indicates that health participation programs in Latin America, in spite of promotional efforts by international agencies, have not succeeded. Then, the article discusses the political objectives behind international support for these programs. It is argued that, through symbolic participation, international agencies had two purposes in mind: the legitimization of low quality care for the poor, also known as primary health; and the generation of much needed support from the masses for the liberal democracies and authoritarian regimes of the region. PMID- 4035408 TI - Fifteen years of community organization for health in Panama: an assessment of current progress and problems. AB - Since the late 1970s the WHO and other international agencies have placed much emphasis on strategies of community organization in order to improve preventive health services and facilities in rural areas. Many countries have recently set out to reform their rural health systems by means of a community-based approach. Panama's 15 years of experience in 'community health' provide insight into the constraints to program continuity at the national level and to maintenance of participatory mechanisms (health committees) at the village level. This paper focuses on the present status of the Community Health Program and level of activity of the health committees. This study is based on in-depth interviewing of key program participants at three contexts: central ministry, district/regional health institutions and rural communities. It sought to discover how interactions among and within these contexts affected program services and community participation. Inconsistent outcomes are evident. In some areas the Community Health Program thrives and the health committees are active, while in most areas the program functions at a minimal level and most health committees are inactive. Several factors are identified which affect a 'successful' or 'unsuccessful' program environment. These include: degree of support from medical directors of district and regional health centers, existence of 'federations of health committees', the extent of political interference, the presence of a functional 'technical health team' and degree of community confidence in health committee officers. PMID- 4035409 TI - Difficulties involved in taking health services to the people: the example of a public health care center in a Caracas barrio. AB - This paper discusses the difficulties faced by a typical Ministry of Health and Social Welfare maternal and infant health care services center. These service modules are usually located in the lower income barrios of Venezuela's urban centers. Recent experiences as seen by supervisors of the regional and district offices of the Ministry and the center's staff were evaluated following in-depth interviews, direct observation and scanning of clinical records over a three month period. The study concludes that the major problem areas influence the Ministry's primary goal of extending coverage to a greater proportion of the needy population and maintain the quality of the services: inadequate administrative structure leading to logistics difficulties; and the clinic location and the characteristics of the barrio itself and of the client population. PMID- 4035410 TI - Coverage and patterns of ambulatory medical care use in Tlalpan, Mexico City. AB - Health officials planned a stepped care system (regionalized) for Tlalpan, in the Federal District of Mexico (D.F.), to address problems of duplicated services, inappropriate use of available resources, increasing costs of medical care, and unmet health needs in the population. Cross-sectional surveys were carried out in the community, in health centers and in hospital based ambulatory services (outpatient department and emergency department) to obtain current, specific and valid information about need and utilization patterns. Users of the various services differed from each other and from the community by age, educational level, occupation, rights to prepaid care and utilization patterns. Emergency department users came back for care repeatedly and sought preventive services from the emergency department. Major reasons for attending the emergency department included respiratory and gastrointestinal problems, plus poisonings, accidents, and complications of pregnancy. Outpatient department users arrived without referral from medical sources and continued to return frequently for care. Users were mostly adults, particularly older adults, with problems of a more chronic nature, e.g. nervous system problems, genitourinary problems, etc. The health centers attended clients from the designated area of influence who had referred themselves to the center for care. Children were the most frequent clients with acute, common problems, e.g. diarrhea and respiratory problems. Health maintenance activities were assessed for which children received the most complete coverage, but some women lacked the necessary care for perinatal health and family planning. In general, health centers seemed to be functioning appropriately, although the magnitude of unattended need in their areas of influence must be investigated further.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4035411 TI - Family medicine: a medical care alternative for Latin America. AB - This paper presents the experience of a residency in family medicine organized 7 years ago by the medical school of the Universidad Autonoma de Nuevo Leon, Mexico. The residency aims to prepare physicians to provide primary health care. In efforts to teach graduate students the social as well as the biological causes of diseases most commonly reported at the primary care level, graduate students take courses in clinical disciplines, social and behavioral sciences and public health. In its training methodology the program combines teaching, service and research. By now, the department of family medicine has graduated five classes of specialists, all of whom are working in the field of family medicine at the primary level. This fact is particularly worth noticing in a country where there are thousands of unemployed/underemployed physicians. It is suggested that family physicians are satisfying an unmet medical demand of many thousands of Mexicans, and that the care provided by them is less expensive and of better quality than the same care provided by other specialists. PMID- 4035412 TI - Mexican immigrants and the utilization of U.S. health services: the case of San Diego. AB - This paper examines survey data gathered from 2103 Mexican immigrants living or working in San Diego County, California, in order to explore four fundamental questions concerning the utilization of health services: (a) What type of health services do Mexican immigrants use? (b) When hospitals are used, do they tend to be emergency room services? (c) Do Mexican immigrants use preventive services? (d) To what extent do the utilization patterns of undocumented immigrants differ from their legally-immigrated counterparts? The socioeconomic profile of the sample is characterized through analysis of variables such as sex, age, length of residence in the U.S., occupation and income. Mexican immigrants, particularly the undocumented, are relatively young compared to the non-immigrant population, of short duration in the U.S. and earn low income. In addition, undocumented and legally-immigrated respondents are covered by medical insurance at rates far below the general population. Mexican immigrants, including the undocumented, use a variety of health services. Hospital services are not the primary source of care. However, when undocumented respondents did use hospital services, they were more likely to use emergency room care than their legally-immigrated counterparts, who were more likely to use out-patient services. Finally, undocumented respondents tended to neglect preventive services as evidenced by examination of the use of pre-natal care, general check-ups and dental services. PMID- 4035413 TI - Unsung questions of medical ethics. AB - Official doctrines of medical ethics have become increasingly 'patient-centered': physicians are exhorted to respect patients' autonomy and to encourage patient participation in decision making; physicians in general medicine and primary care, especially, are urged to develop psychosocial competence, cross-cultural sensitivity and communications skills. These official values are undermined and contradicted, however, by the routines and assumptions that physicians use to organize their everyday work. These routines are taken so for granted as natural and required for the smooth, orderly practice of medicine that they escape evaluation for the implicit values they contain. Yet, they reinforce a particular view of appropriate roles and responsibilities for both physician and patient in the medical system, including the agenda and purpose of the medical interview; the level and amount of information to share with patients; and the power structure of the physician-patient relationship. These values, hidden in the routines of daily practice, are unsung questions of medical ethics. A fallacy in calls for greater patient participation in medical care is that this participation can flourish by simple addition, without reform of the ordinary structures of everyday practice. It is unlikely that these structures will change unless their normally invisible value commitments are drawn out of the obscurity of routine, and made subjects for public scrutiny and choice. PMID- 4035414 TI - Health services and the political culture of Saudi Arabia. AB - Health services occupy a high priority in the development agenda of Saudi Arabia, Saudi culture--devotion to Islam, extended-family values, the segregated status of females and the Al Saud monarchic hegemony--is being formulated in an increasingly deliberate fashion, constituting a new 'political culture' which acts as a screen to insure that technological and human progress remain within acceptable bounds. There is a general disposition on the part of the Saudi populace to use modern health services as these become available, largely under governmental auspice. The role of the government in providing health care for pilgrims during the hajj to Mecca is of particular culture importance. Cultural sensitivities concerning male physicians and female patients will be minimized by the training of a substantial number of Saudi female physicians, whose efforts will be directed toward female patients. At present, most health care in the Kingdom is delivered by male expatriate physicians, as part of the general massive reliance upon expatriate workers: although the expatriates will eventually be replaced by Saudi physicians, this dependency, which is felt to threaten Saudi culture, will continue for a decade or more. Private medicine is rapidly increasing though not on the same scale as government medicine. The provision of government health services is a source of legitimation for the Al Saud regime. In general, health services appear to constitute a form of modernization which meets the test of cultural compatibility. PMID- 4035415 TI - The reinterpretation of Western pharmaceuticals among the Mende of Sierra Leone. AB - The inappropriate use of Western medicines among the Mende of Sierra Leone is addressed as a cultural issue. We show that traditional beliefs about diseases and treatments have provided the explanatory framework for the contemporary Mende in reinterpreting the function of many Western medicines that are available to them. People appear to base their treatment decisions largely on traditional notions of the efficacy of a medicine of a particular color, consistency, taste, size, and reputed success in treating analogous illnesses. This helps to explain why people's uses of these medicines are often at odds with Western manufacturers' assumptions about their appropriate uses. Implications of these uses for local as well as international health are drawn. PMID- 4035416 TI - Traditional infant feeding practices: right or wrong? AB - Infant feeding practices, breastmilk and food intake and post-natal growth in Madura, East Java, Indonesia and Machakos, Kenya are described. Breastfeeding is commonly practised. Additional foods are introduced the first week post-partum in Madura and at age 2-3 months in Machakos. Growth started to falter at 2-3 months in Madura but was acceptable during the first 6 months in Machakos. It was felt that apart from breastfeeding and morbidity, other factors pertaining to mother's perceptions about what infants should eat and her possibility to make suitable weaning foods, should be considered to understand the background of growth faltering. PMID- 4035417 TI - Decision to adopt new medical technology: a case study of thrombolytic therapy. AB - New medical technologies are adopted by practising physicians at varying rates. Thrombolytic therapy is an example of a technological advance that many physicians have seemed reluctant to employ. A random sample of board certified internists was surveyed by mail to study factors that influence decisions to use thrombolytic agents. Variables important in predicting use were identified by discriminant analysis. In general users and non-users had similar assumptions about the risks and benefits of this technology. Among the important predictor variables were a perception of having patients suitable for treatment, availability of the agents and self-rating of knowledge about this therapy. Among questions related to type of practice and education, only subspecialization and textbook reading were important discriminators. These results suggest that decisions to adopt new technologies do not follow simply from risk-benefit assessments. PMID- 4035418 TI - Preventive care attitudes of medical students. AB - Presently developing attitudes of future physicians towards preventive medicine will likely provide either a major impetus for or barriers to the inclusion of preventive medicine content in medical school curricula and in other formats of physician education. In turn, attitudes about preventive care and its role in medical practice will continue to have a large influence on how much disease prevention and health promotion emphasis physicians provide in their practices. Consequently, it becomes important to study how medical students' attitudes evolve during the process of medical education. Furthermore, to the extent that we can better understand how desired attitudes can be developed and nurtured, the practice of preventive medicine may become more purposeful. Beginning and third year medical students were surveyed with a 100-item questionnaire designed to assess their attitudes regarding: the relative importance of 20 specific preventive services to the practice of medicine and the adequacy of preclinical coursework for preparing them to offer preventive care in medical practice. The confidence of third year students' in the ability of primary care physicians to provide these specific services was also assessed. Preventive care service areas about which third-year students expressed high confidence in the ability of physicians to provide were: immunizations, health screening physicals, blood pressure control, cancer detection education, family planning, health counseling/education, and sexually transmitted disease prevention. Services that students had low confidence in the ability of physicians to provide were: smoking cessation, nutrition counseling/education and weight reduction.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4035419 TI - The relevance of the social sciences to health care delivery. PMID- 4035420 TI - Trust, talk and touch in Balkan folk healing. AB - Broadly based in long-term anthropological fieldwork in the Balkans (in Serbia, Macedonia and Bulgaria), this discussion of folk healing techniques illustrates how convergence in the patient/practitioner relationship is of prime importance in effecting a positive outcome. Sumadija in central Serbia is selected as an example, and treatment for erysipelas, a common health problem which villagers call 'the red wind', is described and analyzed. Against a sociocultural background in which the collective wisdom of the past is retained and transmitted orally to contemporary healers, especially to the bajalica, or conjurer who heals with words, it is shown how shared communicative modes of trust, talk and touch are essential to the ritual psychomancy by which the treatment 'works'. Also considered are the ritual roles of women in this patriarchal society and peasants' perceptions of folk pharmacology as being extraneous to the eventual cure. Connections between cultural responses and physiological responses as manifested in the villages are suggested as counterparts of Western symptomatic treatments related to behavior modification. PMID- 4035421 TI - Support networks developed by immigrant women. AB - Women with young children who were immigrants to Canada were interviewed to understand how they defined their needs and what resources they perceived to be available to meet their needs. All of the women described a need to feel as if they belonged in Canada and had people to turn to for personal support. The women identified general groups of people they perceived as able to provide them with differing forms of support. The three groups were labelled; kin, insider and outsider. The women also described how they used the sources of support and the feelings which resulted from their interactions with members of the support groups. The conceptualization which was developed from the data suggests women may follow a pathway in developing a support network. How this information might be used by health professionals in clinical practice is discussed. PMID- 4035422 TI - Social support and learning in preventive health care. AB - This paper analyzes social learning processes in mutual support groups that were developed to facilitate clients' understanding of cardiovascular diseases and their responsibilities for health maintenance. It is based upon a 3-year study of supportive health care in a community of low-income Black and Latino families in south-central Los Angeles, California. Participant-observation and small group research have been employed to understand the learning styles that help chronically ill clients to identity their roles and thereby reduce the anxiety and uncertainty that often accompany a therapeutic regimen. PMID- 4035423 TI - Influences on the antenatal clinic attendance of Central Province women in Port Moresby, PNG. AB - Public antenatal health care services in the National Capital District (NCD) of Papua New Guinea are provided at some of the nurse operated urban satellite clinics and at a large outpatient clinic at Port Moresby General Hospital (PMGH). The major functions of the antenatal clinics are screening for high risk cases and giving routine medications. In this they are following the policy of the National Health Plan and the recommendations of the Public Health Department reports on which it was partially based. The purpose of this study was to examine some of the characteristics of a particular segment of the clientele at the PMGH antenatal clinic and to explore their motivation for attendance, especially the timing of their first visit. After an initial survey of the clinic record cards of all women attending the PMGH clinic in September 1980, interviews were conducted with a stratified sample of women attending clinic sometime between February and June 1981. Only women indigenous to the NCD and the surrounding province were included in the study. From clinic record cards, information was obtained on each woman's residence, birthplace, parity, gestational stage at first clinic visit, place of previous deliveries, clinical/laboratory measures and obstetric history. The interviews were conducted in a private room near the clinic in a language preferred by the interviewee. Their responses clarified some of the background data on their clinic cards and provided additional information on why they came to the clinic when they did. In general, the sample group was highly oriented toward Western-based medical care. They came to have themselves and their babies examined for possible problems, to receive the right amounts of the right medicines, and to get information. This was consistent with both policy and services. They also came because of the perceived effectiveness of the clinic and sometimes because it was the 'proper thing to do'. Many factors influenced their choice of when and where to seek antenatal services, including advice from husbands as well as from traditional female sources. Their previous experiences with hospitals and clinics and with pregnancy in general were also important. PMID- 4035424 TI - The health belief model and preventive health behaviour in Singapore. AB - Every theoretical model in the social sciences confronts a common challenge: to maintain its explanatory power in different cultural contexts. This is, of course, only one of many challenges faced in theory building. But, this discussion shall focus only on the possibility of a cultural bias. More specifically, the aim of this paper is to discuss some of the findings from a test of the Health Belief Model (HBM) in a multi-ethnic society, Singapore. The HBM is a theoretical framework frequently used in the analysis of health-related behaviour. The discussion will be divided into four sections. The first section will present briefly the components of the HBM. The second section will summarize the procedure used to conduct the empirical test of the HBM. And the third and final sections shall deal with the comparison of preventive health behaviour among three ethnic subpopulations in Singapore, highlighting the main findings of the test of the HBM. PMID- 4035425 TI - Changing patterns of modern youth movements. PMID- 4035426 TI - Colonoscopy and the barium enema: a radiologic viewpoint. AB - Adherents of colonoscopy are recommending that it replace the radiologic examination as the initial diagnostic study of the colon. We present the radiologic view, supporting the barium enema as a more practical approach to initial diagnostic evaluation. The radiologic examination is an equally reliable, less costly, and much safer method for detecting colonic disease. PMID- 4035427 TI - Gastroplasty in morbid obesity: observations in 300 patients. AB - Morbid obesity is associated with a number of life-threatening complications. Medical treatment of morbid obesity is rarely successful. Gastric reduction has replaced intestinal bypass as the surgical treatment of choice. Indications for operation are fairly standardized, and complications and results are similar in most large series. In our series of 300 gastroplasties done during the past four years, weight loss compares favorably with that in other reported series. Our hospital complication rate has been low because of short operating time and early ambulation. Postoperative vomiting has been reduced by enlarging the stoma. Revision rate was between 1% and 2% per year. The surgical treatment of morbid obesity requires a great deal of personal contact between surgeon and patient in the preoperative and postoperative periods. Because these patients tend not to comply with the dietary restrictions of the operation, close follow-up care is required. PMID- 4035428 TI - Gallbladder disease related to use of oral contraceptives and nausea in pregnancy. AB - In our series of women with confirmed gallbladder disease, intolerance of oral contraceptives was remarkably high. Among women who did not tolerate oral contraceptives there was a remarkably high percentage of emesis gravidarum. The frequency of cholecystectomy declined substantially between 1971 and 1981. This decrement was especially pronounced in women younger than 40, which could be attributed to the reduced "hormonal load" from both fewer pregnancies and reduced intake of contraceptive steroids. PMID- 4035429 TI - Fine needle aspiration of the lung: a study of 53 consecutive cases. AB - We reviewed our fine needle aspirations of the lung and chest on 53 consecutive patients from January 1979 through June 1982. Almost all of the patients had been studied by sputum and bronchial cytology and many by bronchial or transbronchial biopsy, but none of the patients had a definitive diagnosis. All of the lung aspirates were done in the department of radiology, using a 22 gauge Chiba disposable needle and the Wright-Giemsa stain. Twenty-four cases (45%) were diagnosed as malignant and ten cases (19%) were considered suggestive. Nineteen cases (36%) were read as negative for malignant cells, but in six of these cases (11% of total) we were able to make the diagnosis of an infectious process based on characteristic cytologic findings. PMID- 4035430 TI - Pancreatic cancer: unreliability of frozen section in diagnosis. AB - Thirty-two patients with a resectable mass in the head of the pancreas had pancreaticoduodenectomy for suspected or proven cancer. Twenty-eight proved to have cancer (15 periampullary and 13 pancreatic), and four had pancreatitis. The five-year survival for periampullary and pancreatic cancer was 25% and 0%, respectively. The operative mortality was 19%. There were no false-positive frozen section diagnoses. Seventy-five percent with negative frozen section proved to have cancer, of which 17% were five-year survivors. Surgical judgment based on clinical findings may be more reliable than a negative frozen section in the diagnosis of suspected malignancy. Pancreaticoduodenectomy can be done on the basis of clinical judgment when no tumor is seen on frozen section of a mass in the head of the pancreas. PMID- 4035431 TI - Compensatory growth in infants with severe failure to thrive. AB - We studied compensatory growth and caloric intake during an accelerated growth period of ten infants with severe failure to thrive (FTT). The mean age at diagnosis was 7.1 months (range 1.5 to 16.0 months). The average percentage of normal weight for age in this group was 54.9%, mean length was 58 cm (86% normal for age), and the mean head circumference was 39.7 cm (92% normal for age). Compensatory growth rebound was completed after 6.2 months (range 3.5 to 9.0 months). Minimal calorie counts during peak rate of growth averaged 187 kcal/kg/day (range 147 to 213). The final group average percentage of normal weight for age was 95.5%, an increase of 40%. The group of rebounding infants gained 31 gm/day. The group's length increased to 94% of that expected for age and head circumference to 98% of that expected for age. Like malnourished infants, these with FTT had compensatory growth when managed with ad libitum caloric intake equal to twice the expected intake. PMID- 4035432 TI - Risk of tuberculous infection among house staff in an urban teaching hospital. AB - Physicians in training in our medical center were found to have a higher risk of tuberculous infection than other hospital employees. Their annual tuberculin conversion rate was 3.96%; in two of the 15 recent converters, active disease developed. There is a significant linear relationship between the acquisition of tuberculous infection and the duration of training in an urban teaching hospital. Their compliance rate to annual tuberculin testing and chemoprophylaxis is less than 50%. PMID- 4035433 TI - Descriptive epidemiology of night sweats upon admission to a university hospital. AB - Between March 1 and Sept 1, 1980, we interviewed a 25% random sample of patients admitted to medicine, surgery, and obstetric, and gynecology services to determine the frequency and descriptive characteristics of night sweats (NS). Seventy-two (41%) of 174 patients interviewed reported NS within three months before admission. Obstetric patients reported NS significantly more often than nonobstetric patients (60% vs 33%, P less than .02). The duration of NS ranged from one day to 27 years (mean 10.5 months; median two months). NS were mild in 36 (50%), moderate in 17 (24%), and severe in 19 (26%). Severe NS were reported significantly more often by nonobstetric patients, and most often by those on the medicine service. Among nonobstetric patients, NS were associated with metastatic adenocarcinoma of the prostate gland, and severe NS with the use of antipyretics. NS were not associated with elevated temperature measurements during hospitalization. PMID- 4035434 TI - Primary aldosteronism: computerized tomography in preoperative evaluation. AB - We reviewed the value of computerized tomography (CT) in the preoperative evaluation of 34 patients with primary aldosteronism. All 34 patients entered a standard protocol including saline suppression testing, abdominal CT scanning, and adrenal venous sampling. Surgical pathologic findings, biochemical determinations, and clinical response to adrenalectomy were the criteria used to evaluate 68 adrenals in 34 patients. Of 36 diseased glands 17 were correctly identified by CT (48%). Of the 32 normal glands, 29 were identified correctly by CT (91%). Thus, CT is not sensitive (0.48), but very specific (0.91) in Conn's syndrome. Our patients were divided into two groups: group 1 were those scanned between 1977 and 1980, group 2 were those scanned from 1981 to 1983 with a high resolution GE-8800 scanner. CT results in group 2 showed no significant improvement in specificity (0.92), but improvement in sensitivity (0.58) over group 1 (specificity 0.90, sensitivity 0.42). Furthermore, CT is less sensitive in patients with smaller tumors than in those with larger tumors. PMID- 4035435 TI - Failure of cimetidine as an immunomodulator in cancer patients and normal subjects. AB - Our pilot study of cimetidine as an immunomodulator in cancer patients showed no effect at clinically used doses on total blood, neutrophil, lymphocyte, or monocyte count, quantitative immunoglobulin, percentage of E-rosetting cells, phytohemagglutinin responses or delayed hypersensitivity responsiveness. We concluded that in clinically used doses, cimetidine produces no significant immunomodulation either in vivo or in vitro. PMID- 4035436 TI - Applanation pneumotonometry in screening for glaucoma. AB - Two pneumotonometers were compared to the Goldmann applanation tonometer for adequacy as intraocular pressure screening devices in terms of sensitivity and specificity. The Digilab Model 30D, with digital readout, produced fewer false negative results than the Model 30R, with graph readout, and was thus the more sensitive instrument. Although as a consequence some specificity was lost, this was not considered critical, since in a screening situation, sensitivity is the essential requirement. In addition, with the Model 30R, it was difficult to obtain a valid tracing in 17% of the eyes. PMID- 4035437 TI - Evaluation of the pancreas by endoscopic retrograde cholangiopancreatography and computerized tomography. PMID- 4035438 TI - Pain relief: for cancer victims only. PMID- 4035439 TI - Marrow cell uptake by megakaryocytes and naked megakaryocyte nuclei in routine bone marrow examination. PMID- 4035440 TI - Autoimmune hemolytic anemia associated with a hypernephroma. AB - This report describes a case of warm-antibody-mediated hemolytic anemia associated with a hypernephroma. Only four patients with renal cell carcinoma and Coombs'-positive hemolytic anemia have been reported previously. Although rare, the occurrence of autoimmune hemolytic anemia in association with a hypernephroma should be considered one of the possible hematologic complications of this tumor. PMID- 4035441 TI - Emergency management of tracheal rupture. AB - We have described a patient in whom tracheal rupture occurred during prolonged mechanical ventilation. Appropriate intensive respiratory care management, including the use of the minimal leak technique, was used. Our patient unfortunately had nearly every known predisposing factor for tracheal damage. PMID- 4035442 TI - Herpes simplex esophagitis in healthy adults. AB - Herpes simplex virus may cause esophagitis, usually in patients with malignant neoplasms or immunocompromise. We have reported three cases of herpes simplex esophagitis in healthy young men, all of whom had positive mucosal biopsy culture for herpes simplex virus. All three patients recovered quickly without specific therapy. PMID- 4035443 TI - Lactobacillemia in pregnancy. AB - A pregnant woman allergic to penicillin was successfully treated with erythromycin for pyelonephritis and bacteremia caused by Lactobacillus. PMID- 4035444 TI - Sarcoidosis: a cause of bilateral hilar lymphadenopathy after excision of malignant melanoma of the arm. AB - Bilateral hilar lymphadenopathy developed in a patient one year after excision of a malignant melanoma of the left arm. There were no signs of distant metastases. Hilar lymph node biopsy specimen obtained by mediastinoscopy showed multiple noncaseating granulomas consistent with sarcoidosis, without evidence of tumor cells. Sarcoidosis developing in the course of a preexisting neoplasm is rare, but must be considered in order to establish a proper diagnosis and withhold unnecessary treatment. PMID- 4035446 TI - Stubborn otitis externa. PMID- 4035445 TI - Pacemaker-associated sepsis: successful medical management. AB - We have presented a case of Staphylococcus aureus septicemia in a patient with a transvenous pacemaker who responded to conservative medical therapy. PMID- 4035447 TI - "Love Boat" hepatitis. PMID- 4035448 TI - Nonresolving Cushing's syndrome due to depot methylprednisolone verified by high performance liquid chromatography. PMID- 4035449 TI - The public image of psychiatry. PMID- 4035450 TI - Unemployment and male-female labor force participation as determinants of changing suicide rates of males and females in Quebec. PMID- 4035451 TI - The Social Interview Schedule (SIS)--content, structure and reliability. PMID- 4035452 TI - Housing type, housing location and mental health. PMID- 4035453 TI - [Sociological study and typological analysis of a population of drug addicts in outpatient care]. PMID- 4035454 TI - A cross-cultural study of confidentiality. PMID- 4035455 TI - Determination of treatment disposal for parasuicide patients in a German university hospital. PMID- 4035456 TI - [Long-term results of the surgical treatment of pancreatic pseudocyst]. PMID- 4035457 TI - [Therapeutic tactics in rectal cancer in advanced age]. PMID- 4035458 TI - [Reconstruction of a traumatic defect of the diaphragm using an artificial prosthesis in an experiment]. PMID- 4035459 TI - [Extra-anatomic bypasses in reconstructive arterial surgery]. PMID- 4035460 TI - [The effect of phenothiazines on reperfusion of the ischemic myocardium]. PMID- 4035461 TI - [The technic of phenolization of fistulae in pilonidal cysts]. PMID- 4035462 TI - [External fistulae of the digestive tract]. PMID- 4035463 TI - [Postcatheterization thrombosis of the femoro-iliac veins in children]. PMID- 4035465 TI - [Gout and urolithiasis]. PMID- 4035464 TI - [Possible errors in the diagnosis of Bochdalek's congenital diaphragmatic hernia]. PMID- 4035466 TI - [A study of amyloidogenesis in relation to SAA levels in inflammatory diseases]. PMID- 4035467 TI - [Basal ganglia calcification in two children with systemic lupus erythematosus and neuropsychiatric manifestations]. PMID- 4035468 TI - [Circulating immune complexes in rheumatoid arthritis--their association with IgM rheumatoid factor, anatomical stages and functional classes]. PMID- 4035470 TI - The undergraduate student and the study of ophthalmology. PMID- 4035469 TI - Antimicrobial prophylaxis in surgery. PMID- 4035471 TI - Pulmonary rupture caused a rapid decompression of a post-lobectomy pneumothorax. PMID- 4035472 TI - The adult tethered cord syndrome. PMID- 4035473 TI - Legal and ethical obligations and medical training. PMID- 4035474 TI - Changes in infant mortality rates among whites, coloureds and urban blacks in the RSA over the period 1970-1983. AB - Using national mortality statistics, we found that infant mortality rates (IMRs) declined among whites and coloureds in the RSA over the period 1970-1983, the decrease in coloured IMR being from 134,8 to 50,7/1 000 and that in white IMR from 21,6 to 12,6/1 000. The decrease in the IMR among coloureds was mainly due to the decline in post-neonatal mortality rates (PNMRs). Since post-neonatal deaths are generally due to gastro-enteritis, pneumonia, malnutrition and measles, the decline in mortality is probably due to a decrease in these causes. The decrease in early neonatal mortality made only a small contribution to the decline in the IMR among coloureds. In the case of whites the decrease in the IMR was largely due to the decline in the early neonatal mortality rate (ENMR); these deaths usually result from low birth weight, the respiratory distress syndrome, asphyxia and infections. The decline in the PNMR played a minor role. National IMRs for blacks are not reported annually, but IMRs can be calculated for the two census years 1970 and 1980 for blacks in 34 'selected' (urban) magisterial districts, and were 124,4 and 85,9/1 000 respectively. A valid IMR for 'rural' Transkei from a well-conducted epidemiological study was 130/1 000 in 1980. The components of the IMRs for blacks can only be determined for certain urban areas with large black populations such as Soweto (adjacent to Johannesburg), where the IMR fell from 81,4/1 000 in 1970 to 25,5/1 000 in 1983. The decline in the IMR was due to decreases in both the ENMR and the PNMR.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4035475 TI - The epidemiology of accidental poisoning in children. AB - During a 1-year period (1 March 1982-28 February 1983) 272 children were admitted to the Red Cross War Memorial Children's Hospital, Cape Town, after accidental poisoning. More boys than girls were admitted, and children between the ages of 12 months and 3 years were the most vulnerable. More than half the patients were coloured; blacks and whites represented minorities. Most cases appear to occur during the summer months (November, December and January). Medicines were responsible for most cases of accidental poisoning in whites and coloureds, but household preparations were responsible for most cases in blacks. The above findings are compared with previous yearly statistics. PMID- 4035476 TI - Hypertension in white South African miners. AB - A study was undertaken to determine the prevalence of hypertension among white South African miners, examine risk factors for hypertension, identify adverse outcomes of hypertension, and evaluate the extent and efficacy of treatment for hypertension. A total of 11686 miners was assessed. The prevalence of hypertension was comparable to that in three occupational groups in the USA and probably comparable to a group of urban males in Durban, although differences in methods did not allow precise comparison with this population. Obesity was an important risk factor. Electrocardiographic abnormalities, especially premature ventricular contractions, right and left bundle-branch block and myocardial infarction, were associated with elevated first recorded blood pressure. Of the 468 miners in the cross-sectional study who stated that they were taking antihypertensive medication, only 30% had diastolic blood pressures lower than 90 mmHg. PMID- 4035477 TI - The effect of cholecystectomy on bile reflux. An experimental study. AB - In an experimental study the effect of cholecystectomy on bile reflux into the stomach was investigated. Five dogs were used and a large number of bile reflux measurements carried out (115 tests). During each test, reflux was measured over a continuous period of 6 hours by estimating the concentration of bile phospholipids (lecithin and lysolecithin) in the gastric juice. The pre cholecystectomy phospholipid concentration in the stomach was 7,751 +/- 1,621 mg/dl (mean +/- SEM) and the post-cholecystectomy concentration 35,181 +/- 10,653 mg/dl (P less than 0,05). Two dogs developed gastric mucosal changes, mainly foveolar hyperplasia. The importance of measuring reflux repeatedly over long periods of time in order to get a more representative picture of reflux is stressed. PMID- 4035478 TI - The modified vital index in prehospital emergency care. AB - Many vital indices and scores have been proposed and used, particularly in relation to trauma. Most were primarily designed for and, within limits, are successful in hospital application. Attempts to use all or part of these in the prehospital context are misguided. There is a major difference between this phase of emergency care and hospital care, and that is the inability to provide a definitive end-point of treatment. A new score is proposed, the modified vital index (MVI) based on vital signs and other parameters important in the prehospital context. The value of the MVI lies in its adaptability to emergency medical care systems at all stages of development. The necessity for the MVI is outlined, as is the detailed working of the system. The hope is expressed that through adaptation of the MVI in different areas a consolidated prehospital scoring system may be achieved. PMID- 4035479 TI - A profile of 125 women requesting reversal of sterilization. AB - A series of 125 consecutive requests from patients in a private practice for reversal of sterilization has been analysed. Most of the women (65,6%) had changed their marital status since the sterilization, 93,9% of these having been divorced (most of whom remarried--73,1% of the new husbands being younger than their wives and 89,6% marrying for the first time) and 6,1% widowed. In the 34,4% in whom there had been no change in marital status, a reappraisal and the wish to have another baby, sometimes consequent upon the death of a child (16,3%) or an improvement in health (7,0%) led to the request for reversal of sterilization. At the time of sterilization 64,8% of the women had been under the age of 30 years, and 82 (65,6%) had not had a stable marriage. This indicates that very careful counselling should be carried out before sterilizing patients, and also before considering reversal of the operation. PMID- 4035480 TI - A consumer approach to a paediatric assessment clinic. AB - The past 20 years have witnessed a revolution in the treatment of mentally retarded children. Initially, parents received very little help after the diagnosis was made. Towards the end of the 1960s parents were trained in techniques devised by professionals. A new concept, called the 'consumer model', where parents form an important part of the caring team in selecting a programme best suited to their current needs, is at present developing. With this in mind a survey was carried out by the Assessment Clinic at the Transvaal Memorial Institute for Child Health and Development, Johannesburg, to ascertain parents' needs and their opinions of the service received at the clinic. Thirty-seven parents were interviewed using a structured questionnaire. The results are discussed and the subsequent changes made at the clinic presented. The need for an ongoing evaluation of such a service is emphasized. PMID- 4035481 TI - Cholera in children at Eshowe Hospital. AB - During a 2-week period in May 1983 Eshowe Hospital inpatients were screened for cholera and positive cases were found on all the wards that were investigated. The high incidence among paediatric patients suggested the possibility of an epidemic in the community and/or cross-infection within the ward. At this time 9 paediatric nurses were found to have cholera-positive stools and subsequently 8 children contracted cholera after admission to hospital. The possibility of cross infection by person-to-person transmission is suggested. In the second part of this study, our clinical experience of cholera among inpatients during the period January 1983 - March 1984 is reviewed. The number of children in hospital with cholera-positive stools decreased sharply during the winter months; this was possibly related to variations in both temperature and rainfall. The full range of symptomatology was seen and several children had repeated episodes of proven cholera. The mortality was highest in bottlefed babies who were malnourished or under 1 year of age. Between 30 May and 15 June 1983, 293 consecutive children attending the paediatric outpatients department were screened for cholera; 99 cases were confirmed. Thus cholera was shown to be present in the paediatric community outside Eshowe Hospital. Diagnosis based on the history and clinical findings proved unreliable and laboratory investigation was essential. Rivers were the most common and dangerous source of domestic water. The majority of accompanying adults questioned were using untreated water or failing to treat the water adequately.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4035482 TI - The present and future role of general practice surgery. AB - In the RSA a general practitioner may perform any operation he feels competent to do. This contention is discussed, the type and frequency of operations performed by GPs is described, and the changing role of general practice surgery, its medicolegal implications, and the experience and training needed are outlined. PMID- 4035483 TI - Aims and attitudes--teaching primary health care at UCT. AB - The objective of this study was to determine the attitude of student interns completing their exposure to primary health care (PHC) to: (i) the need for the teaching of PHC; (ii) whether or not the aims of the block had been realized in their case; (iii) the tutors as clinicians and as teachers; (iv) the structure of the exposure; and (v) the PHC emphasis they would have liked. Of a class of 188 student interns, 156 completed an attitude questionnaire (a statement is given and students indicate whether they agree, disagree, or are uncertain). It was found that 96% wanted teaching in PHC, 90% thought that they had improved their skill in assessing and managing PHC problems, 82% thought that they had improved their consultation technique, 88% thought that their tutors were competent clinically and 79% that they were competent as teachers, 61% wanted more exposure to Third World PHC, 47% wanted more exposure to Western family practice, and 41% were dissatisfied with sections of the exposure. An attitude survey can provide useful feedback from student interns on the relevance, aims, effectiveness, structure and teaching of PHC block. PMID- 4035484 TI - Mismatched blood transfusion. A case report. AB - Blood transfusion reactions due to mismatching are fortunately very rare. A case of a patient being given incompatible blood to correct postoperative anaemia is reported and the management discussed. PMID- 4035485 TI - Left atrial myxoma in a 13-month-old infant. AB - The presentation, diagnosis and management of a 13-month-old child with a left atrial myxoma is described. The value of echocardiography in confirming the diagnosis is emphasized. PMID- 4035486 TI - Beriberi heart disease. A case report describing the haemodynamic features. AB - Beriberi heart disease should be considered in all patients with cardiac failure and a history of alcohol abuse or dietary deficiency. We studied the haemodynamic changes which took place immediately after intravenous administration of thiamine to a patient with high-output beriberi. Cardiac output and stroke volume fell rapidly, but not below normal levels, and systemic vascular resistance rose. PMID- 4035487 TI - Hamartomas of the head and neck. A report of 4 cases. AB - Hamartomas in the head and neck region are unusual, and few reports of such lesions are found in the literature. Four cases of hamartoma are described. Two were lymphoid hamartomas (1 occurred in the neck and 1 in the parotid gland), the third was a vascular hamartoma of the ethmoid, and the fourth was found in the neck and was composed of cartilage and fibrofatty tissue. PMID- 4035488 TI - Teaching and practice dichotomies. PMID- 4035489 TI - Black mamba envenomation. PMID- 4035490 TI - Safer blood--supplementation of blood products with anti-HBs. AB - An enzyme-linked immunosorbent assay (ELISA) was developed for the detection and quantitation of antibodies (anti-HBs) to the surface antigen of the hepatitis B virus (HBsAg). The ELISA uses HBsAg as the solid phase, and, after conjugation to horseradish peroxidase, also as the conjugate. Conditions for this assay were optimized and a rapid (1.5 hours) ELISA has evolved which works very satisfactorily for the large-scale screening of donated blood. We have used this ELISA to examine donated blood in Natal and concluded that we cannot initiate a programme of anti-HBs supplementation of parenteral blood products without hyperimmunization and plasmapheresis of selected, voluntary donors. PMID- 4035491 TI - Value of glycosylated haemoglobin determination in diabetic pregnancy. AB - A single measurement of total maternal glycosylated haemoglobin (Hb A1) in the late third trimester of a diabetic pregnancy is of limited value in assessing diabetic control. There was no significant correlation between maternal Hb A1 values and neonatal C-peptide values or birth-weight ratios. An isolated Hb A1 measurement is not sufficiently sensitive to monitor the control of diabetes during pregnancy nor is it useful in predicting perinatal outcome. PMID- 4035492 TI - Cancer of the cervix. Some aspects of epidemiology, screening, risk factors and survival. AB - Early statistics on the occurrence of cancer of the cervix are unreliable. What is certain is that between 1950 and 1965 incidence rates (IRs) and mortality rates (MRs) fell considerably in most Western populations. Recently, however, rates in the 15-35-year age group of some populations have risen two- to threefold. In some developing populations, especially in South America and Africa, rates are very high--up to eight times those in most Western populations. Risk factors include early age at first intercourse, low socio-economic state, having multiple partners, smoking, being widowed or divorced, and having a husband who has had multiple partners. The modus operandi of carcinogenesis is not known. Screening, using the Papanicolaou test, has markedly reduced the IRs and MRs, particularly in certain Scandinavian populations. In Western populations 40-60% of patients attain 5-year survival. Understandably, in individual patients the crucial regulating factor is the stage of disease when diagnosed. Among those at stage I, 70-90% survive for 5 years or more, whereas only 0-25% of patients diagnosed at stage IV do. In Soweto, Johannesburg, length of survival in a series of black patients whose staging pattern did not markedly differ from that in Western series was less than half that in the latter. Undoubtedly, as repeatedly urged, appropriate selective screening and health education could effectively reduce the toll of mortality, especially in high-risk developing populations. PMID- 4035493 TI - [Abdominal aorta aneurysm in aged patients. Is an operation worthwhile?]. AB - Although abdominal aortic aneurysm (AAA) is an unpredictable and sometimes fatal condition, it can be cured, and studies have indicated that improved peri operative care has led to a lowering of the operative risk in the elderly. In this study mortality after AAA repair was 3,8% in patients over 60 years compared with 3,2% in those under 60 years. Eighty-seven per cent of the over-60s regained their physical capacities after the operation, and 92% considered the operation to have been worth while. A plea is made that all patients with AAA be referred to a hospital for objective evaluation of the operative risks with a view to elective surgery, since the mortality from ruptured aneurysms is still in the region of 50%. PMID- 4035494 TI - Blood lead levels in a remote, unpolluted rural area in South Africa. AB - The whole-blood lead levels of 14-16-year-olds in a remote, unpolluted rural area (Wupperthal, north-western Cape Province) were determined. Graphite-furnace atomic absorption spectrometry was used to analyse lead levels. The mean whole blood lead level was found to be 3,4 micrograms/dl. This value should also be considered to be representative of the natural 'background' whole-blood lead level of South Africans. PMID- 4035495 TI - AIDS--its implications for South African homosexuals and the mediating role of the medical practitioner. AB - The concerns of people affected by the current 'AIDS scare' are discussed from a holistic point of view, incorporating medical, psychological and social factors. Parameters of homosexual experience are described fully. The medical practitioner is encouraged to obtain an extensive psychosexual history from concerned patients on the guidelines presented. AIDS is a community health issue in which the medical practitioner plays a pivotal role in diagnosis, counselling, referral and patient education. PMID- 4035496 TI - Kaposi's sarcoma of the oral cavity. A case report. AB - A case of Kaposi's sarcoma of the oral cavity in a 54-year-old black man is reported. The possible association with acquired immune deficiency syndrome is emphasized and the diagnosis, treatment and prognosis of oral Kaposi's sarcoma are discussed. PMID- 4035497 TI - Painful muscle spasm reversed by magnesium sulphate. A case report. AB - A 25-year-old paraplegic man who had sustained a T3/T4 vertebral compression fracture 3 years previously presented with severe, painful spasm of the left hamstring muscle group of 2 hours' duration. This spasm produced extreme knee flexion of a degree which held the left foot posterior to the right buttock. An intravenous injection of 2 g magnesium sulphate produced immediate relief. Possible mechanisms of action of magnesium are discussed. PMID- 4035498 TI - Rectal spirochaetosis--symptomatic response to metronidazole and mebendazole. A case report. AB - A white homosexual man presented with a 6-week history of intermittent diarrhoea, abdominal pain, nausea and malaise. Threadworm infestation was present, but other gastro-intestinal infection was excluded. Rectal spirochaetosis was found on examination of a rectal biopsy specimen. The patient's symptoms disappeared and the rectal tissue returned to normal on biopsy after treatment with metronidazole and mebendazole. It is suggested that the symptoms were directly related to the presence of rectal spirochaetosis, which responded to the antibiotic. PMID- 4035499 TI - Systemic nodular panniculitis (Weber-Christian disease) in a black woman. A case report. AB - There are many causes of panniculitis and systemic nodular fat necrosis; Weber Christian disease is one of the rarer forms. A 47-year-old black woman with Weber Christian disease is described and the aetiology, pathology and clinical manifestations of the disease are discussed. PMID- 4035500 TI - Oxytocin-induced water intoxication. A case report. AB - Oxytocin-induced water intoxication is an uncommon iatrogenic condition with serious potential morbidity and mortality, which is preventable with a rational approach to therapy. Its pathogenesis, management and prevention are discussed. PMID- 4035501 TI - Clinical manifestations of Cape cobra (Naja nivea) bites. A report of 2 cases. AB - Two cases of proven bites by the Cape cobra (Naja nivea) are reported. Both patients developed areflexic flaccid paralysis and required ventilation from 2 1/4 and 2 1/2 hours after the bite for 4 1/2 and 7 days respectively. Antivenom is of value before the onset of paralysis but of no value once paralysis is established. Both patients developed a non-depolarizing neuromuscular block which was little affected by prostigmine. Early treatment in identified Cape cobra bites should be the immediate application of an arterial tourniquet, followed by intravenous administration of 80-100 ml polyvalent antivenom if signs of neurotoxicity develop. This may need to be repeated. Treatment once paralysis is established is largely supportive, prolonged ventilation frequently being required, following which recovery should be complete. PMID- 4035502 TI - Aspiration of oral contents in Parkinson's disease. A case report. AB - A patient with Parkinson's disease developed a non-ketotic hyperosmolar diabetic coma precipitated by chest infection. Initial improvement from treatment with intravenous insulin, ampicillin and fluid therapies was followed by severe deterioration and hypovolaemic shock. Further improvement occurred only when therapy directed against Gram-negative sepsis was added. A barium examination later demonstrated aspiration of oral contents with pulmonary soilage. The differences between the easily recognized early fulminating 'aspiration syndrome' caused by aspiration of gastric contents of low pH and the aspiration of oral contents, which may remain occult for many hours, is highlighted. Life threatening Gram-negative or anaerobic infection may then occur but remain undiagnosed because the original aspiration of foreign material is unsuspected. PMID- 4035503 TI - Lysis of a coronary embolus by intracoronary streptokinase. A case report. AB - A patient presenting with an acute myocardial infarction, probably caused by a coronary artery embolus after aortic valve replacement, was treated by intracoronary thrombolysis with streptokinase. Restoration of antegrade flow in the previously totally occluded vessel was followed by an uncomplicated recovery and evidence of good preservation of left ventricular function. PMID- 4035504 TI - Fatal thrombo-embolism after limb exsanguination. A case report. PMID- 4035505 TI - Inadvertant intrathecal administration of magnesium sulfate. PMID- 4035506 TI - Social class classification in the RSA--a comparison of four ethnic groups. PMID- 4035507 TI - Radiological diagnosis of traumatic hernia of the left diaphragm. PMID- 4035508 TI - Clinical effects of epidural block during labour. A prospective study. AB - The aim of this study was to evaluate the clinical effects of epidural block for pain relief during labour in an obstetric unit which manages mainly high-risk pregnancies. In the majority of the 62 patients studied only 5 ml of a 0,5% solution of bupivacaine was sufficient for effective pain relief. In 75% of patients total pain relief was obtained. Complications of the procedure were hypotension in 32% of patients and bladder atony needing catheterization in 19%. The mean fall in blood pressure was greater in patients with pre-existing hypertension. The incidence of instrumental delivery was 40%, inadequate bearing down effort being the indication in 54% of these cases. An abnormal fetal heart rate pattern on cardiotocography developed in 13 of 58 fetuses who were monitored internally, while in 3 cases an abnormal pattern because even more abnormal (in one-third of these cases this followed hypotension in the mother). The only statistically significant change in fetal heart rate patterns on cardiotocography was a decrease in the beat-to-beat variability. Epidural block is a very effective form of pain relief during labour but has potentially serious effects, especially in high-risk pregnancies. Precautions to minimize the risk of complications include the administration of intravenous fluid before the procedure and careful monitoring of the patient and her unborn baby. A cardiotocographic monitor is essential for the latter purpose. PMID- 4035509 TI - The pattern and frequency of congenital heart disease among blacks. AB - The types of cardiac malformations in 804 black patients of all ages in whom the diagnosis was confirmed by cardiac catheterization, surgery or autopsy are reported. The most frequent anomalies were ventricular septal defect, patent ductus arteriosus and tetralogy of Fallot. Among infants under 1 year of age, complete transposition of the great vessels accounted for the third-largest group of malformations. While pulmonary venous anomalies were extremely rare and hypoplastic left heart defects rare in the neonate, it is not considered that a racial predilection for differences in the frequency of various cardiac malformations exists. The frequency of coarctation of the aorta in the group as a whole was not lower than that found in studies among whites. Among black patients of all ages with heart disease (studied in a hospital environment) congenital cardiac malformations ranked as the second most common form of heart disease with a frequency of 26%. Among children aged 15 years or less, congenital heart disease ranked first with a frequency of 53%. It is suggested that a diagnosis of congenital heart disease is not made in the majority of blacks born with such malformations. PMID- 4035510 TI - The irritable bowel syndrome--a study from private practice. AB - The clinical features of 150 consecutive patients with irritable bowel syndrome are reported. All patients were referred to a private practice. There was a marked female preponderance and a wide range of ages. Diarrhoea was predominant in 61,3%. The common symptoms were altered bowel habit, abdominal pain, emotional disturbance, flatulence and distension. Fatigue, weight loss, upper gastrointestinal symptoms, backache and urinary symptoms were frequent. The rectum showed nonspecific loss of vascular pattern, oedema and congestion in 11,4% of patients, but this was readily distinguished from inflammatory bowel disease on histological examination. The incidence of non-smokers in the group was 78,1%. The overall appendicectomy rate was 34%, and 65% of the 92 women had had gynaecological operations. A positive diagnosis was made on a typical history and simple basic investigations. More extensive investigations were required for those patients with markers of organic disease, but these yielded few associated lesions. PMID- 4035512 TI - Intussusception in black children. AB - Seventy-six black patients with intussusception are reviewed. Infants (59%) presented with features similar to classic intussusception; ileocolic lesions were most common (80%) and a high resection rate (36%) was the sequel to delay in presentation. Children over 2 years of age (41%) presented with a pattern of 'tropical' intussusception in which primary colocolic lesions predominated (55%) and leading points were rare (3,5%). A high percentage of older children appears to characterize series from tropical areas. The relative proportions of these groups may vary between, and within, geographical regions and differing causes are likely. However, the management of both groups is similar. Hydrostatic reduction was not effective in those patients in whom it was attempted. PMID- 4035511 TI - Zinc and copper levels in the breast-milk of Cape Town mothers. AB - Zinc and copper levels were measured longitudinally in the breast-milk of 55 healthy South African women from the middle and upper socio-economic classes. The mean foremilk zinc levels showed a significant fall (P less than 0,05) from 652,9 +/- 240,7 micrograms/dl at 3 days after delivery to 413,3 +/- 143,0 micrograms/dl at 7 days and 228,1 +/- 136,1 micrograms/dl at 6 weeks. Lower foremilk zinc levels were obtained at 36 weeks (64,3 +/- 50,0 micrograms/dl). In contrast, foremilk copper levels were low at 3 days (57,0 +/- 74,8 micrograms/dl), with a gradual decline to very low levels (28,0 +/- 29,7 micrograms/dl) at 36 weeks. No differences were detected between the fore- and hindmilk zinc and copper levels at any stage of lactation studied (P greater than 0,05). PMID- 4035513 TI - Oesophageal lesions at autopsy in black children. AB - Oesophagi of black children dying from a variety of diseases examined at autopsy showed features of chronic oesophagitis and atypical basal cell hyperplasia in a significant percentage of cases. The possible significance of this finding in relation to carcinoma of the oesophagus is discussed. PMID- 4035514 TI - The value of X-ray pelvimetry in previous caesarean section pregnancies. AB - The results of erect lateral X-ray pelvimetry in a retrospective study of 100 randomly selected patients who had undergone previous caesarean section for a variety of indications were analysed. The indication for caesarean section was compared with subsequent pregnancy outcome. The inlet diameter and sacral shape were not found to be of great predictive value. Radiological engagement of the fetal head was associated with a 90% incidence of vaginal delivery. PMID- 4035515 TI - Non-accidental injuries among Indian children in Durban. AB - This first prospective study of child abuse among Indian children in the RSA reports 44 cases seen at the R.K. Khan Hospital in Chatsworth, Durban, over a 3 1/2-year period. Over a third of the patients were under 6 years of age. Most of the injuries were minor bruises involving the face, head and lumbar region, while there were 8 cases of sexual abuse. The victim's father was the abuser in 36,3% of cases, followed by the mother in 20,5%. The main environmental risk factors were marital discord, divorce, extramarital affairs, wife-battering, unemployment, receipt of disability or other grants, poor living conditions, and drug and/or alcohol abuse. PMID- 4035516 TI - Anaesthetic management of a difficult intubation. AB - Intubation management of a patient with polyostotic fibrous dysplasia is described. The principles in planning for a difficult intubation are discussed. PMID- 4035517 TI - Actinomadura pelletieri mycetoma from the Transvaal. A case report. AB - The osteophilic red grain mycetoma due to Actinomadura pelletieri is rare in southern Africa. This report describes an elderly patient with extensive bone involvement in which lymphatic spread to the inguinal lymph nodes had occurred. The diagnosis and management are discussed. PMID- 4035518 TI - Ependymal cyst of the ovary. A case report. AB - An unusual morphological variant of a mature cystic teratoma was found at caesarean section in a 23-year-old patient; it appeared as a thin-walled cyst containing clear fluid. Microscopy showed the cyst to be lined by ependyma and the wall to be composed of glial tissue with a small protuberance containing squamous epithelium, adipose tissue and bone. PMID- 4035519 TI - Spontaneous contained transmural oesophageal rupture clinically resembling intramural rupture. A case report. AB - Spontaneous rupture of the oesophagus may occur either transmurally or intramurally. The symptoms, signs, clinical course, treatment and prognosis differ in the two types. Transmural rupture is generally regarded as a serious condition, usually requiring operative treatment and having a high morbidity and mortality. Intramural rupture is a much more benign condition, is treated non operatively and has a good prognosis. A few cases have been documented in which a transmural rupture was contained within the mediastinum; an additional case is described. Under these circumstances the transmural rupture has the clinical features of an intramural rupture. It is suggested that transmural ruptures should be subdivided into those which are not contained (the vast majority) and those which are. PMID- 4035520 TI - Sarcoidosis in Ciskei. A report on 15 cases. AB - Since 1977 15 patients with sarcoidosis have been seen at the Cecilia Makiwane Hospital, Ciskei. Three patients were 13 years of age or less and 5 were under 20 years; 6 patients had phalangeal osteolytic lesions, 5 with concomitant skin involvement. Only 3 patients had respiratory symptoms. PMID- 4035521 TI - Gonococcal vulvovaginitis among female children in Malaysia. AB - In this retrospective review of 16 children with vulvovaginitis due to Neisseria gonorrhoeae, the authors attempt to estimate the incidence of this infection and to ascertain the routes of transmission. From January 1977 to December 1982, 422 cases of gonococcal vulvovaginitis in women of all age groups were encountered at the University Hospital, Kuala Lumpur, Malaysia. Of these, 406 cases (96.2%) occurred in adults, and 16 cases (3.8%) occurred in children younger than 12 years of age. Penicillinase-producing N. gonorrhoeae (PPNG) strains were isolated from five (31%) of the 16 girls; all five cases were subsequently treated with cefuroxime and probenecid. The rest responded to intramuscular procaine penicillin. Although all patients appeared to be cured, only ten of 11 (two with PPNG) had test-of-cure cultures performed after treatment. Although interviewing the parents revealed no history of sexual contact in these children, nine of the girls were linked to culture-positive adult(s). PMID- 4035522 TI - Absence of progesterone effects on chlamydial genital infection in female guinea pigs. AB - The effect of progesterone alone and in combination with estradiol was investigated in ovariectomized and gonadally intact female guinea pigs infected with the chlamydial agent of guinea pig inclusion conjunctivitis (GPIC). The course of the infection, as determined by the percentage of cells with GPIC (chlamydia) inclusions in Giemsa-stained vaginal scrapings, was not affected in animals receiving 5.0 mg of progesterone daily. Progesterone had no influence on the enhancement of infection by estradiol. In comparison with sesame oil-treated controls, infection was prolonged by four to six days (P less than .05) in animals receiving a combination of 5.0 mg of progesterone plus 1.0 microgram of estradiol or 1.0 microgram of estradiol alone each day. In ovariectomized animals, estradiol delayed the appearance of IgA antibody in genital secretions, whereas progesterone alone had no effect. Guinea pigs treated with estradiol or progesterone plus estradiol manifested an acute endometritis not observed in animals treated with progesterone alone or in controls receiving sesame oil. Although cervical ectopy, analogous to that seen in women with high levels of progesterone, was identified by histopathology in animals treated with progesterone, no enhancement of the chlamydial infection was observed. PMID- 4035523 TI - Contraceptive practices of women attending the Sexually Transmitted Disease Clinic in Nashville, Tennessee. AB - The decision to be sexually active involves two health risks for women: unwanted pregnancy and sexually transmitted diseases. Use of contraception affects both these risks. Data from the Metropolitan Health Department in Nashville, Tennessee, were examined to determine the effects of particular contraceptive methods on gonococcal infection in women. The results suggest that not only barrier methods but also other types of contraception were associated with protection against gonorrhea in females. The use of contraception was unusually high (87%) among the study population of 1,303 women. Five hundred eighteen (40%) of these clinic attendees were infected with Neisseria gonorrhoea. Infected women tended to be younger than those not infected and were significantly more likely to be black than white and somewhat more likely to be single. Contraceptors tended to be younger and were more likely to be black than were noncontraceptors. PMID- 4035524 TI - [In vitro culture of the pluripotent stem cell of human bone marrow (CFU-GEMML). Technical, morphological, conventional and cytochemical aspects]. PMID- 4035525 TI - [Trends in leukemia mortality for child and adolescent age groups in Spain (1951 1979)]. PMID- 4035526 TI - ["Benign" monoclonal gammopathy: prognostic value of initial bone marrow study]. PMID- 4035527 TI - [Haptoglobin: review and new perspectives]. PMID- 4035528 TI - [Bone marrow pseudoparasitization]. PMID- 4035529 TI - [Reversible reticulin myelofibrosis associated with pernicious anemia]. PMID- 4035530 TI - Assets of new retired-worker beneficiaries: findings from the New Beneficiary Survey. AB - Most new retired workers in 1982 owned some type of asset, usually a savings, checking, or credit union account, according to data obtained by the Social Security Administration (SSA) in its New Beneficiary Survey. Many recently retired workers also owned their home, often mortgage-free. Homeownership was their most significant asset in terms of its median value. Comparatively few retirees owned property other than a home, though for owners of such property, the median value was substantial. Married couples, whose assets included those of both partners, more frequently owned assets and their assets had higher median values than did unmarried individuals. A comparison of retired workers with persons aged 65 or older who were enrolled in the Medicare program but who had not yet received retired-worker benefits showed that these Medicare-only enrollees were much better off, both in the likelihood of owning assets and in having higher median values for their assets. Individuals who retired before reaching age 65 and therefore received a reduced social security benefit were not as well off as those whose first benefit was paid at age 65 or older. Overall, the asset situation of new retired workers in 1982 was better than that of men and unmarried women aged 58-63 in 1969, even when the 1969 assets were adjusted to constant 1982 dollars. PMID- 4035531 TI - Income of new retired workers by age at first benefit receipt: findings from the New Beneficiary Survey. AB - Using data from the New Beneficiary Survey (NBS) of the Social Security Administration (SSA), this article examines how income sources and total monthly income received by newly retired social security beneficiaries vary with the age at which the first benefit check was received. The NBS respondents who received a first benefit at age 65 or older were better off economically than were those who received a first benefit at ages 62-64. At the time of the interview, 18-30 months after receiving a first benefit, these older beneficiaries had higher levels of total income and were more likely to have income from earnings and assets. Pension receipt rates did not vary by the age at which the first social security benefit was received except for married women retired workers, for whom the rate was higher at the older ages. The largest proportion of aggregate income (slightly more than one-third) was derived from social security benefits. More than 90 percent of the NBS Medicare-only respondents--a sample of nonbeneficiaries who were eligible for monthly cash benefits but had established their entitlement only for the purpose of enrolling in the Medicare program- reported earnings income. They had lower rates of pension receipt and higher rates of asset income receipt than the retired workers. The Medicare-only respondents had substantially higher incomes than did retired workers, and most of their aggregate income was from earnings. The NBS retirees were generally in better financial condition than a group of social security beneficiaries aged 65 or older from all benefit categories in the Current Population Survey Income Supplement with whom they were compared. PMID- 4035532 TI - The patient has a family: reaffirming social work's domain. AB - Work with the family has traditionally been claimed as the domain of social work within the hospital setting. The difficulties of expanding the scope of clinical work to systematically include the family and its needs as integral to meeting the patients' psychosocial needs can be attributed in part to the absence of a conceptual model that encompasses the patient, the impact of the illness, the family and the hospital. The authors propose a paradigm to address these multiple variables with their attendant treatment implications. PMID- 4035533 TI - Families, transitions, and health: another look. AB - This paper critically reviews the Caroff-Mailick classification of families seen around health care crises, and of reciprocal roles suggested for health social workers depending on severity and trajectory of illness and on family's functioning levels. As balance, transitional crisis theory, holistic health concepts, and team approaches to the mobilized family as the unit of caregiver attention are discussed. Newer alternative family styles are reviewed which challenge middle class caregiver mores and practices. Family forces which may prejudice worker assessment are reviewed, and the need to mitigate unhealthy and constricting environmental conditions is stressed. PMID- 4035534 TI - Social work with cancer patients: stresses and coping patterns. AB - This article reports a study of the special stresses affecting the increasing number of social workers who work with cancer patients and their families. Related literature and research document the universally stressful effects of this chronic and life-threatening illness but offer little knowledge of the job stresses experienced by social workers providing services in hospitals. The nature of the stresses reported by social workers, the adequacy of supports to help them cope with the emotional impact of their work and the need for additional support programs are discussed. PMID- 4035535 TI - Surgical treatment of supraventricular tachyarrhythmias. AB - The surgical treatment of supraventricular tachyarrhythmias has undergone considerable evolution since its inception in 1968 with the treatment of a patient with Wolff-Parkinson-White syndrome. At present, Wolff-Parkinson-White syndrome, atrioventricular node re-entry, and ectopic atrial foci that can be localized are all amenable to surgical therapy. PMID- 4035536 TI - Thermal injury in the pregnant patient. AB - Thermal injury sustained during pregnancy presents special management problems for both the gravid woman and her unborn child. Of 6,573 admissions to this burn center during the period of 1950 through 1982, 1,157 (17.6 per cent) were female and 448 (6.8 per cent) were of reproductive age. Thirty of this latter group (6.7 per cent) of burned patients were pregnant at the time of injury. These 30 patients ranged in age from 16 to 37 years old (an average of 22.7 years) and the burned portion of the total body surface area ranged from 6 to 92 per cent (an average of 39.7 per cent). A review of the clinical courses of these 30 patients suggests several observations and conclusions. Pregnancy does not alter the maternal outcome after thermal injury and maternal survival is usually accompanied by fetal survival in the absence of significant complications. If the injury of the gravid patient is lethal, the pregnancy will usually terminate spontaneously prior to her death. Obstetric support and aggressive fetal monitoring is recommended for all moderately and severely burned pregnant patients. Obstetric intervention may be considered in the ill patient with a near term fetus in whom significant complications (such as, hypotension, hypoxemia or sepsis) jeopardize the life of the fetus. PMID- 4035537 TI - An anatomic investigation of radical resection of tumor in the hepatic duct confluence. AB - The fetal umbilical vein in the ligamentum teres can be reopened to provide a 10 centimeter long vein, as wide as the left portal vein or the central splenic vein, that gives access to the left portal vein in the umbilical fissure of the liver. By cutting the ligamentum teres, this potential autologous venous graft is lost and, therefore, the ligamentum teres should never be sacrificed without reason. The umbilical side of the reopened umbilical vein can be anastomosed with the splenic vein to form a portal vein bypassing conduit that enters the liver in the umbilical fissure and take over function of the portal vein. From the results of this postmortem investigation, it can be concluded that radical block resection of the area consisting of the hepatic duct confluence, classic right hepatic lobe and complete hepatoduodenal ligament, preceded by construction of a complete separate afferent blood supply of the classic left hepatic lobe, is possible both anatomically and technically. There is no indication denying the supposition that the result of such a procedure is functionally analogous to standard extended right lobectomy with bilioenteric reconstruction. PMID- 4035538 TI - Naloxone does not prevent death after rapid hemorrhage in swine. AB - Despite the array of hemorrhage models, animal species and experimental designs, it seems clear that naloxone with or without volume replacement has no place in the treatment of rapidly exsanguinating traumatized patients. In this situation, the adrenergic hemodynamic effects, indirectly due to naloxone, further decrease tissue perfusion leading to a deleterious outcome. We suggest that the membrane stabilizing effects rather than the hemodynamic effects of naloxone should be pursued in the treatment of low perfusion states with longer survival times than rapid hemorrhage, such as septic and cardiogenic shock. PMID- 4035539 TI - Cardiovascular alterations in severe pregnancy-induced hypertension seen with an intravenously given hydralazine bolus. AB - The acute cardiovascular effects of a 10 milligram bolus of hydralazine was found to cause a significant increase in heart rate and cardiac index while decreasing mean arterial pressure and systemic vascular resistance index. A wide spectrum of individual responses was seen in terms of peak effects and duration of effects. The role of hydralazine in patients with severe pregnancy-induced hypertension was discussed and possible alternative therapy is suggested. PMID- 4035541 TI - Appendicitis in children. AB - Six hundred and fifty-one patients with appendicitis were reviewed and an over all perforation rate of 36.5 per cent accompanied by a major complication rate of only 3.38 per cent and an over-all complication rate of 9.06 per cent was reported. This low complication rate despite a high level of perforation can be attributed to the use of antibiotic regimens effective against both aerobic and anaerobic organisms. A thorough irrigation and flushing of debris and exudate from the abdominal cavity of patients with ruptured appendicitis may improve these rates. PMID- 4035540 TI - Biologic considerations regarding the one and two step procedures in the management of patients with invasive carcinoma of the breast. AB - Investigation of the biologic significance of delay between biopsy and mastectomy was performed upon women with invasive carcinoma of the breast in protocol four of the NSABP. Since the period of delay was two weeks or less in approximately 75 per cent, no comment concerning the possible effects of longer periods can be made. Life table analyses failed to reveal any difference in ten year survival rates between patients undergoing radical mastectomy management by the one and two step procedures. Similarly, no difference in adjusted ten year survival rate was observed between women managed by the two step procedure who did or did not have residual tumor identified in the mastectomy specimen after the first step or biopsy. Importantly, the clinical or pathologic stages, sizes of tumor or histologic grades were similar in women managed by the one and two step procedures minimizing selection bias. The material used also allowed for study of the possible causative role of biopsy of the breast on the development of sinus histiocytosis in regional axillary lymph nodes. No difference in degree or types of this nodal reaction could be discerned in the lymph nodes of the mastectomy specimens obtained from patients who had undergone the one and two step procedures. This finding indicates that nodal sinus histiocytosis is indeed related to the neoplastic process, albeit in an undefined manner, rather than the trauma of biopsy per se as has been suggested. These results do not invalidate the use of the one step procedure in the management of patients with carcinoma of the breast. Indeed, it is highly likely that it will be commonly used now that breast-conserving operations appear to represent a viable alternative modality for the primary surgical treatment of carcinoma of the breast. Yet, it is apparent that the one step procedure will be performed for technical and practical rather than biologic reasons. PMID- 4035542 TI - Non-left sided diaphragmatic rupture due to blunt trauma. AB - An analysis of the clinical, diagnostic and therapeutic features of non-left sided diaphragmatic rupture due to blunt trauma to the torso was performed in ten patients. All patients had multiple systems involved. False-positive peritoneal lavage occurred in three patients (37.5 per cent). The correct diagnosis was made only once preoperatively; diaphragmatic rupture usually being an incidental finding at celiotomy or thoracotomy. Mortality is high and is a manifestation of associated injuries. PMID- 4035543 TI - A new method for securing oral esophageal tamponage tubes. PMID- 4035544 TI - Endoscopic guided intubation of long nasointestinal decompression tube. AB - Surgeons have long been faced with the problem of intubating long nasointestinal tubes through the pylorus of the stomach when intestinal obstructions are present. The procedure described herein provides a direct view of intubation, endoscopically, rather than a blind approach fluoroscopically. This is achieved in every instance through the use of a guided wire inserted through an endoscope with a sleeve type, long nasogastrointestinal decompression tube. The procedure has proved to be advantageous because of the time saved by providing for rapid passage and prompt decompression which also eliminates trips and calls to the radiology department. Also, the improved condition of the patient prior to operation and the decreased amount of radiation that the patient is exposed to are advantages. PMID- 4035545 TI - A method for replacement of the endotracheal tube with continuous control of the airway. AB - A technique has been described which allows replacement of endotracheal tubes, while maintaining control of the airway, using a fiberoptic bronchoscope. The technique was successful in 27 of 29 attempts. While this method does not replace elective tracheostomy, it is indicated for critically ill patients requiring urgent replacement of endotracheal tubes in whom anatomic considerations preclude conventional methods. PMID- 4035546 TI - A new technique for mesenteric catheter plication for recurrent advanced obstruction of the small intestine. AB - Various modifications of the Noble plication procedure have proved to be good techniques and each has its specific indications and complications. The mesenteric catheter plication technique was devised to provide a simple, safe and effective alternative to those previously described. Thus far, it has appeared to function as anticipated. PMID- 4035547 TI - Overall results in 304 consecutive patients with acute spontaneous subarachnoid hemorrhage. AB - The results obtained in 304 consecutive patients with spontaneous subarachnoid hemorrhage are described, the majority of whom (86%) were admitted while in acute condition. Only 46% of the patients in this series were in good condition at admission. The initial management was standardized for all patients, but the protocol of "delayed surgery" was applied to patients with subarachnoid hemorrhage from aneurysmal rupture. Two hundred and twenty-two patients (73%) had intracranial aneurysms. Of these, 20 (9%) were moribund and died shortly after admission; nine (4%) underwent emergency surgery due to the coexistence of a life threatening cerebral hematoma; seven (3%) were operated upon within 3 days of admission; 78 (35%) died after rebleeding or after steady deterioration of the patient's condition due to vasospasm while awaiting surgery. Of the remaining 108 patients ready for delayed surgery, 12 (11%) (operation refused, elderly patients in poor general condition, spontaneous thrombosis of the aneurysm) were treated conservatively, and 96 (89%), who were in various clinical conditions, were actually operated on. Of these 96 patients, 79 (82%) exhibited excellent or good results, 5 (5%) were disabled, and 12 (12%) died. In the authors' experience, the overall management of intracranial aneurysms in unselected patients according to the protocol of delayed surgery results in significant loss of patients awaiting surgery, and good surgical results in the survivors. PMID- 4035548 TI - Drill burrs for anterior decompression of the spinal cord--a new device. AB - We have devised a new drill burr that is particularly suitable for an anterior approach to the spinal cord. The drill burr is conical in shape, with a shaft attached to its top and fine diamond edges on the curved slope, but not on its tip. The bone is scraped off while the burr is being gently pulled up but not pressed down. This new drill burr has proved to be most useful in safely removing osteophytes and hypertrophied uncovertebral joints without damaging the already compromised spinal cord. PMID- 4035549 TI - Experimental model for internal repair of arteriovenous fistulas. AB - An artificial arteriovenous fistula was created by performing an end-to-side anastomosis between the anterior facial vein and carotid artery of the rat. An intraarterial venous graft was then used to seal the fistula. In 8 of 10 rats, carotid artery flow was found to be maintained as judged by angiography, carried out 14 days after the operation. The fistula remained closed in each case. The vessels were also examined with a scanning electron microscope. PMID- 4035550 TI - Transpetrosal-transtentorial approach and its application in the therapy of retrochiasmatic craniopharyngiomas. AB - Our experience with the transpetrosal-transtentorial approach to retrochiasmatic craniopharyngiomas is herein reviewed and an operative technique is described. Excellent exposure of the retrochiasmatic and suprasellar regions is gained with a minimal retraction of the temporal lobe and cerebellum. Eight cases of retrochiasmatic craniopharyngiomas that extended into the posterior hypothalamus were operated on utilizing this approach. The operative results were excellent in five patients, good in one, and poor in one. There was one death later. The principal advantage of this technique is that it allows the hypothalamus, even in cases in which the structure is remarkably displaced upwards, the third ventricular walls in cases of the intraventricular extension of the tumor, and the inferior surface of the optic chiasma and nerves to be visualized directly and thus safely preserved. PMID- 4035551 TI - Combined trigeminal and glossopharyngeal neuralgia. AB - A case of combined trigeminal and glossopharyngeal neuralgia is described. The superior cerebellar artery and normal choroid plexus compressed and indented the root entry zones of the trigeminal and glossopharyngeal nerves, respectively. Complete relief was obtained after microvascular decompression and resection of the choroid plexus. PMID- 4035552 TI - Extraaxial ependymoma of the posterior fossa. AB - A case of extraaxial ependymoma of the posterior fossa, arising along the inferolateral aspect of the left cerebellar hemisphere, is reported. The clinical, radiologic, and histologic features of this lesion are presented. The unusual location of the tumor and its possible origin are discussed in the light of previous experience with other extraaxial ependymomas of the neuraxis. PMID- 4035553 TI - Cerebral cladosporiosis. AB - A 49-year-old woman was admitted to Hacettepe Medical Faculty Hospital with the complaints of headache, nausea, vomiting, lethargy, and weakness on her right side. She revealed a history of pulmonary Cryptococcus infection 5 years before and she had been treated with amphotericin B. After clinical and laboratory investigation she was thought to have an intracranial mass, but her deteriorating situation did not allow any surgical intervention; she died within 7 days. On necropsy, hard, gray-white nodular pulmonary lesions, ranging 0.1-4 cm in diameter, basal meningitis, infarcts, and a nodular lesion 1.5 cm in diameter similar to those of the lung were present in the white matter of the right hemisphere of the brain. Microscopic examination revealed granulomatous inflammation caused by Cladosporium, which had brown pigment and septate hyphae. PMID- 4035554 TI - Extracorporeal circulation with deep hypothermia and circulatory arrest in the treatment of intracranial arterial aneurysms. AB - Extracorporeal circulation with circulatory arrest and deep hypothermia in surgery on certain giant intracranial arterial aneurysms or on aneurysms difficult to access is described. The series includes a giant left carotid aneurysm, an aneurysm of the basilar artery bifurcation, a patient with two aneurysms, one on the right middle cerebral artery and the other at the end of the basilar artery, and a fourth patient with two aneurysms, one on the right middle cerebral and the other on the right carotid. Closed-thorax extracorporeal circulation with femoral cannulation was performed on all the patients. Surgical procedure is described and the advantages and disadvantages discussed. Results are encouraging. The authors suggest that the technique be used during surgical treatment of certain intracranial aneurysms that are in awkward positions or are very large in size. They emphasize that the procedure should be confined to exceptional cases. PMID- 4035555 TI - Long-term growth hormone responses to nonspecific hypothalamic hormones in acromegalic patients. AB - Nonspecific hypothalamic hormones such as thyrotropin-releasing hormone or luteinizing hormone-releasing hormone, or both, elicited abnormal growth hormone responses in 73 of 108 (67.6%) acromegalic patients. After transsphenoidal adenomectomy, the provocative tests using these hormones were repeated in 26 patients with abnormal preoperative growth hormone responses to study variations in these responses during a 1-8-year observation period (average duration, 4 years). After surgery, 7 of the 26 patients regained normal basal growth hormone levels (less than 5 ng/mL) and manifested normal responses to the hypothalamic hormones. During the postoperative observation period, their basal growth hormone levels remained normal as did their responses to provocation with hypothalamic hormones, confirming that the adenoma had been completely resected. Eight other patients demonstrated normal growth hormone levels after surgery; however, they continued to have abnormal responses to provocation with hypothalamic hormones, suggesting the presence of residual adenomatous tissue in the gland. These patients manifested no marked increase in basal or peak growth hormone levels during the follow-up period (from less than 1 to less than 7.5 years) and they were all in clinical remission without any other treatment. Only one incompletely adenomectomized patient who had received no additional treatment experienced regrowth of the tumor. The main factor affecting the surgical results appears to be the preoperative basal growth hormone level, because abnormal growth hormone secretion ceased in all patients who had manifested preoperative levels below 45 ng/mL. Technical refinements of the operative procedure are another important factor in the postoperative outcome. Peritumoral tissue resection after simple selective adenomectomy is mandatory for better surgical results. Our studies indicate that fairly good results can be obtained without risk of the recurrence of the tumor or regrowth, when postoperative growth hormone levels are below 5 ng/mL and that the results are not affected by the postoperative growth hormone responses to provocation with hypothalamic hormones. PMID- 4035556 TI - Mixed colloid cyst-xanthogranuloma of the third ventricle. A light and electron microscopic study. AB - A mixed colloid cyst-xanthogranuloma of the third ventricle is described. The xanthogranuloma associated with the cyst completely occupied the third ventricle. On light microscopy, a single epithelial layer with a basal lamina was seen lining the cyst wall. Electron microscopic study revealed three different kinds of cells in the epithelial layer: ciliated, nonciliated, and basal cells. Many lipid droplets were present in the superficial epithelial cells, macrophages, pericytes, and endothelia. The pathogeneses of the cyst and of the xanthogranuloma are discussed. PMID- 4035557 TI - Ectasia of the basilar artery with special reference to possible pathogenesis. AB - The pattern of reticular fibers and some other microscopic features of all the major intracranial arteries were examined in two patients with ectatic basilar artery. In order to make a comparison possible the major cerebral arteries of 105 individuals with advanced atherosclerosis were also investigated. This series includes 40 patients with berry aneurysms. Defects in the elastic lamina and reticular fiber deficiency in the muscular layer were common pathologic features in patients with ectatic basilar artery and in those with berry aneurysm. In the ectatic basilar arteries these alterations were much more conspicuous. In the other atherosclerotic arteries sampled from patients having no malformations, the density of reticular fibers in the media was preserved. It is concluded that atherosclerosis may not have a basic role in the pathogenesis of arterial ectasias, but the severe reticular fiber deficiency in the media associated with extensive defects in the elastic lamina forms the morphologic basis of ectasias. Furthermore, the arterial ectasias and berry aneurysms are most probably different manifestations of the same underlying disorder. PMID- 4035558 TI - Intraocular tamponade and surface tension. AB - Surface tension is an important property of substances used as intraocular tamponades. The physical properties of currently available intraocular tamponades (gases, silicone oil and Healon) are compared with emphasis on surface tension. The gas/water interface surface tension is the greatest and therefore is the most effective in closing retinal breaks (70 erg/cm2). This is followed by silicone oil/water interface surface tension (50 erg/cm2). Healon is a 1% solution of water and therefore has no surface tension. Practical and theoretical considerations of various tamponades are described. Some properties of an ideal tamponade are suggested. PMID- 4035559 TI - Branch artery occlusion in a young woman. AB - A 31-year-old woman presented with signs and symptoms of anterior and posterior cerebral circulatory insufficiency. The differential diagnosis and therapeutic options are discussed. The most likely cause is a cardiogenic source of emboli. PMID- 4035560 TI - A pituitary adenoma with dilated ventricles. AB - It is generally accepted that postoperatively radiographic examinations be limited to the area of pathology. The patient presented here complained of visual difficulties two years after transphenoidal removal of a pituitary prolactinoma. His endocrinologist ordered what he believed to be the appropriate computed tomography study and the neuroradiologist did not correctly interpret the new finding of dilated ventricles. Subsequently, a second primary tumor was discovered, a pineal gland sarcoma. The patient had refused radiotherapy after removal of his prolactinoma. Had he not, his second tumor would probably have been attributed to radiation. It is interesting to speculate whether radiation scatter from treatment of the prolactinoma would have prevented the pineal gland sarcoma. PMID- 4035561 TI - Increased dependence of leucine in posttraumatic sepsis: leucine/tyrosine clearance ratio as an indicator of hepatic impairment in septic multiple organ failure syndrome. AB - The body clearance of 10 plasma amino acids (AA) was determined from the rate of compared muscle-released AA and AA administered by infusion of total parenteral nutrition (TPN) compared to their estimated extracellular (ECW) pool in patients with multiple trauma with (n = 10) or without (n = 16) sepsis at 8-hour intervals. In both nonseptic and septic trauma, increasing TPN increased the mean clearance rate of all infused AA. When the individual AA clearance rates were normalized by the total AA infusion rate, regression-covariance analysis revealed that patients with sepsis had relatively impaired clearances of alanine (p less than 0.01) and methionine, proline, phenylalanine, and tyrosine p less than 0.05 for all). In contrast, the clearances of branched-chain AA (BCAA) valine and isoleucine were maintained, and the clearance of leucine was higher (p less than 0.05) in trauma patients with sepsis than in those without. At any AA infusion rate, compared with surviving patients with sepsis (p less than 0.05), patients who developed fatal multiple organ failure syndrome (MOFS) showed increased clearances of all BCAA with further impaired clearance of tyrosine. The clearance ratio of leucine/tyrosine was increased in MOFS at any AA infusion rate (p less than 0.0001), was an indicator of severity, and, if persistent, was a manifestation of a fatal outcome. Because tyrosine metabolism occurs almost entirely in the liver while leucine can be utilized by viscera and muscle, these data suggest early and progressive septic impairment of the pattern of hepatic uptake and oxidation of AA with a greater body dependence on BCAA, especially leucine, as septic MOFS develops. PMID- 4035562 TI - Alterations in amino acid clearance during ischemia predict hepatocellular ATP changes. AB - Although decreases in hepatic adenosine triphosphate (ATP) levels during ischemia are thought to reflect loss of hepatic energy reserves and decreased viability, such changes have not been correlated with a clinically relevant index of hepatic function or viability. Ability to clear amino acids from plasma has been shown to correlate with function of the allograft in hepatic transplantation and survival after portal decompression in patients with hepatic cirrhosis. The effects of 60 minutes of warm ischemia in two groups of mongrel dogs were studied to assess the relationship between loss of ATP and amino acid clearance. One group (shunted) had portal decompression during the ischemic period and the other (portal stasis) did not. There was a significant correlation between loss of ATP and amino acid clearance after ischemia. Although the effects of ischemia on the liver were similar in both groups, the portal stasis group demonstrated significantly elevated SGOT levels during reperfusion that were related to impaired net adenine monophosphate synthesis and suggestive of ongoing injury. These data support the contention that loss of ATP during ischemia is associated with reduced functional capacity. In addition, they suggest that portal stasis produces toxic products that can impede hepatic recovery from ischemia. PMID- 4035563 TI - In vivo measurement of leucine metabolism with stable isotopes in normal subjects and in those with cirrhosis fed conventional and branched-chain amino acid enriched diets. AB - Low plasma levels of branched-chain amino acids, leucine, isoleucine, and valine are postulated to play an etiologic role in hepatic encephalopathy. Supplementation is advocated to reverse encephalopathy and improve nutritional status and survival. We measured in vivo leucine metabolism in normal individuals (n = 5) and in two groups of patients with cirrhosis (n = 8) with a primed continuous infusion of L-[15N, 1-13C] leucine to quantitate the following parameters of leucine metabolism: nitrogen and carbon fluxes, oxidation, contribution to protein synthesis, breakdown of endogenous protein to leucine, deamination and reamination to/from ketoisocaproate. Studies were performed in the fasting and fed states with a conventional enteral diet (Propac) and a branched chain-enriched diet (one third Propac plus two thirds Hepatic-Aid). In vivo leucine metabolism was similar in the fasting and fed states in normal individuals in patients with cirrhosis and with both diets when studied at a protein intake of 0.6 gm/kg ideal body weight/day. When fed these diets, oxidation increased (p less than 0.05) and breakdown decreased (p less than 0.05). The Hepatic-Aid diet increased (p less than 0.05) nitrogen and carbon fluxes significantly more than did the standard diet. Four additional patients with cirrhosis on a diet with more protein were studied (0.75 gm/kg ideal body weight/day). Carbon and nitrogen fluxes, oxidation, synthesis, and deamination were increased (p less than 0.05) when patients with cirrhosis were fed the Propac diet compared with those who fasted. The Hepatic-Aid diet further increased (p less than 0.05) all parameters except synthesis and did not decrease protein breakdown. These data show that patients with cirrhosis metabolize leucine in vivo in a manner identical to that of normal subjects and that leucine enriched formulas increase oxidation to CO2 without improving protein synthesis. PMID- 4035564 TI - Effect of aging on gallbladder contraction and release of cholecystokinin-33 in humans. AB - The objective of this study was to examine the effect of aging on gallbladder contraction and cholecystokinin (CCK) release, as well as on the correlation between the two in humans who are free of gallbladder disease. Twenty-nine human volunteers were divided into a young group of 14 individuals (ages 22 to 42 years, median age 32 years) and an older group of 15 individuals (ages 60 to 84 years, median age 66 years). In the study each person in both groups was given corn oil (Lipomul), 1.5 ml/kg, by mouth after an overnight fast. Blood was collected for measurement of CCK-33 by radioimmunoassay before and at intervals after ingestion of Lipomul. Simultaneous measurements of gallbladder volume were obtained by real-time varian ultrasonography. Both fasting and fat-stimulated concentrations of CCK in plasma were significantly higher in the older individuals than in the younger volunteers. The 60-minute integrated measurement of CCK release was significantly increased in the older people as compared with the young. Both fasting and maximally contracted gallbladder volumes were equal in the older and younger groups. The rate of emptying of the gallbladder was equal in both age groups, but the gallbladders of older people appeared to show an earlier initiation of contraction. The highly significant correlation of gallbladder contraction with levels of CCK was similar in both age groups, but the sensitivity of the gallbladder to CCK in the older people was significantly decreased. In conclusion, both fasting and fat-stimulated plasma levels of CCK increase with aging. The sensitivity of the gallbladder muscle to stimulation by CCK is diminished with age, but this appears, teleologically, to be matched by the increased release of CCK, so the kinetics of gallbladder emptying are little different in the aged. PMID- 4035565 TI - Can gastrointestinal hormones enhance intestinal absorption? AB - Recent studies have suggested that certain gastrointestinal peptides exert a trophic effect on the small intestine. We chose to evaluate the effect of glucagon and cholecystokinin-octapeptide (CCK-OP) on absorption of substrates in both developing and mature small intestine. Developing small intestine was evaluated in a rat fetal intestine transplant model, and mature rat small intestine was studied in in situ but isolated 10 cm segments of jejunum and ileum. Glucagon, 10 micrograms/kg/day, and CCK-OP, 45 micrograms/kg/day, were delivered continuously for 14 days through a subcutaneous osmotic pump. Intestinal absorption was determined with labeled substrates (14C-galactose and 14C-glycine) by a recirculation perfusion technique. Absorption results were expressed as percentage increase over control. The fetal intestine response to glucagon infusion was a 13% rise in galactose absorption and a 27% rise in glycine absorption. After CCK-OP infusion, fetal galactose absorption was 11% and glycine absorption rose 17%. Mature jejunal galactose absorption rose 53% and glycine absorption rose 55% after glucagon infusion. The ileal response to glucagon was a 271% rise in galactose absorption (p less than 0.05) and a 21% increase in glycine absorption. Infusion of CCK-OP decreased jejunal galactose absorption 3% but increased glycine absorption 41%. The ileal response was a 224% increase in galactose absorption (p less than 0.05) and a 19% increase in glycine absorption. Our data suggest that chronic administration of glucagon and CCK-OP can increase substrate absorption in developing and mature rat small intestine. Perhaps manipulation of the gastrointestinal hormone environment may result in increased absorption in man. PMID- 4035566 TI - Increases in gallbladder prostaglandin synthesis before the formation of cholesterol gallstones. AB - Increased synthesis of prostaglandins in the wall of the gallbladder may play a role in the pathogenesis of cholesterol gallstones by mediating mucus hypersecretion and thereby accelerating nucleation and the precipitation of cholesterol-supersaturated bile. We induced gallstones in prairie dogs and guinea pigs by feeding a cholesterol-supplemented diet for periods as long as 6 weeks. Gallbladder prostaglandin synthesis was quantitated by specific radioimmunoassays that measured the amount of various prostanoids released from the gallbladder during in vitro incubation. The gallbladders of cholesterol-fed prairie dogs showed increased synthesis of prostaglandin E2, prostaglandin F2a, and thromboxane and increased concentrations of glycoprotein in gallbladder bile. These changes were evident as early as 2 weeks after institution of the cholesterol diet, although cholesterol gallstones did not form until 4 or more weeks. In contrast, cholesterol feeding of the guinea pig did not induce cholesterol supersaturation. In this species pigment gallstones formed, probably as a result of a cholesterol-induced hemolytic anemia, and gallbladder mucus hypersecretion did not occur. Pigment gallstone formation in the guinea pig was associated with an increase in prostacyclin synthesis, but the synthesis of prostaglandin F2a and thromboxane was decreased. Increased prostaglandin synthesis may contribute to the formation of cholesterol gallstones but does not appear to participate in pigment gallstone formation. PMID- 4035567 TI - Gallbladder filling and response to cholecystokinin are not affected by vagotomy. AB - We studied the effects of vagotomy on gallbladder (GB) motility in prairie dogs and humans with infusion cholescintigraphy. Twelve male prairie dogs were anesthetized and given an intravenous infusion of 120 microCi of diethyl-HIDA for 150 minutes. Images were acquired every 10 minutes. Then cholecystokinin (CCK)-8, 1.5 micrograms/kg, was given as a bolus, and images were acquired for another 30 minutes. We repeated the studies giving 300 micrograms/kg of atropine 20 minutes before administration of CCK-8. All animals underwent truncal vagotomy, and the studies were repeated 1 and 3 months later. The GB filled in a stepwise fashion; partitioning of bile varied from one 10-minute period to the next and averaged 20% +/- 2%/80% +/- 3% during the 150-minute period. Episodic partial GB emptying (ejection fraction 19% +/- 2%; intervals of 70 +/- 5 minutes) occurred during this phase. GB filling and partitioning of bile were unchanged after vagotomy. GB ejection fraction in response to CCK-8 was 69% +/- 6% in controls, 74% +/- 5% after atropine, 78% +/- 8% 4 weeks after vagotomy, and 66% +/- 6% 3 months after vagotomy. Sixteen human subjects were studied after parietal cell vagotomy (six patients) or truncal vagotomy and drainage (10 patients). GB filling average 2.5% +/- 2% per minute in patients who underwent truncal vagotomy and 3% +/- 1% per minute in patients who underwent parietal cell vagotomy. GB emptying in response to CCK-33 (0.02 U/kg/min) was 74% +/- 7% in patients who underwent truncal vagotomy and 82% +/- 4% in patients who underwent parietal cell vagotomy. Thus neither GB filling nor GB emptying in response to CCK was altered by cholinergic blockade or vagotomy. PMID- 4035568 TI - Inhibition of bile flow by intravenous arginine hydrochloride. AB - One proposed mechanism for the cholestasis associated with total parenteral nutrition is infusion of amino acids. Arginine, 19 mumol/kg/min, was infused for a short time in healthy dogs with a biliary fistula to test the effect of endogenous hormone release on bile flow and composition. Both plasma glucagon and blood glucose levels increased. Despite the release of the choleretic hormone, glucagon, bile flow decreased 30%. The suppression of bile flow was attributed to a decrease in the bile acid-dependent fraction of bile flow. Bile acid, cholesterol, and phospholipid output were all depressed. PMID- 4035569 TI - Carotid endarterectomy in a metropolitan community: comparison of results from three institutions. AB - The hospitalizations of 300 patients who had carotid endarterectomies (CEA) in three different kinds of hospital were analyzed. 100 patients had CEA performed by experienced vascular surgeons in a university hospital (UH), 100 patients had CEA performed by experienced vascular surgeons in private community hospitals (PCH), and 100 patients had CEA performed by senior general surgery residents (GSR) assisted by experienced vascular surgeons in a university-affiliated Veterans Administration hospital (VA). Analysis of patient characteristics revealed that, compared with the other groups, VA patients were (1) younger (62 +/- 7 years; p less than 0.001); (2) had a higher frequency of peripheral vascular operations (51%; p less than 0.01; (3) were more often cigarette smokers (84%; p less than 0.001); and (4) had more contralateral carotid occlusions (19%) and ulcerated lesions (73%) (p less than 0.01). GSR had longer operating room times and cerebral ischemia times during shunt insertion and removal (6 +/- 2.8 minutes) and during the CEA (30 +/- 27 minutes) (p less than 0.001). Postoperative hypertension and neck hematomas were less common in PCH patients (p less than 0.001) than in the other groups. Although their duration of hospitalization (17 +/- 12 days) was longer, the VA patients experienced no increased morbidity. There was a high rate of cranial nerve injury in all groups (27%, 15%, 17%) but symptoms were not often permanent (9%, 6%, 6%). Our data indicate that results of vascular operations performed by well-supervised residents are comparable in all important respects to those performed by fully trained surgeons. PMID- 4035570 TI - In utero supplemental fetal feeding in an animal model: effects on fetal growth and development. AB - That the fetus swallows amniotic fluid and has the capability of intestinal absorption of protein and carbohydrate is known, but its significance in fetal nutrition is not clear. We have infused nutrient solutions of dextrose and amino acids intra-amniotically in a chronic third-trimester fetal rabbit model and examined the effects on fetal growth and development. Over a 5-day period, 26 fetal rabbits received graded doses of dextrose in water with or without amino acids infused continuously into the amniotic space. At the time of delivery, fetal body, liver, and brain weight, crown-rump length, and brain protein content were significantly higher in the infused rabbits than in noninfused controls. Amniotic fluid, serum, and gastric content glucose levels were significantly higher in infused fetuses. There was a linear relationship between nonprotein calories administered and fetal growth within the infused group. No toxicity of infusates in the fetus was noted, although technical complications relating to the infusion apparatus were common. We conclude that third-trimester intra amniotic infusion of nutrient solutions enhances fetal growth in this rabbit model. We speculate that this technique may be of value in the antenatal treatment of growth-retarded fetuses. PMID- 4035571 TI - Age, gender, lateral dominance, and prediction of operative skill among general surgery residents. AB - Ability patterns and surgical proficiency were examined in matched groups of general surgery residents selected on the basis of age, gender, or hand preference from a population of 141 residents who had completed neuropsychologic tests of visuospatial, psychomotor, and stress tolerance abilities and had been rated on 12 aspects of technical skill exhibited during 1480 operative procedures. Older residents (ages 28 to 42 years) exhibited less motor speed (p less than 0.05) and coordination (p less than 0.005) and more caution in avoiding psychomotor errors (p less than 0.05) than did their younger counterparts. No differences were found for visuospatial abilities, stress tolerance, or rated surgical skill. These findings indicate that although age does appear to adversely affect pure motor skills, these are not important components of operative proficiency. Female residents exhibited superior (p less than 0.05) academic achievement (MCAT, Verbal and National Boards Part II) as compared with their male counterparts. They also excelled on a signal detection task requiring identification of visual patterns. However, the women scored less well (p less than 0.05) than men on a visuomotor task demonstrated to be a significant predictor of operative skill. Greater cautiousness in avoiding errors may be a contributing factor to their reduced efficiency on this task. In comparison to male controls, female residents received consistently lower surgical skills ratings, particularly on items measuring confidence and task organization. Left handed residents were more reactive to stress (p less than 0.03), more cautious (p less than 0.04), and more proficient on a neuropsychologic test of tactile spatial abilities (p less than 0.03) than right-handed counterparts. Although these traits correlated positively (p less than 0.05) with rated operative skill within the left-handed group, the group received consistently lower ratings than did right-handed residents. The inconvenience of assisting left-handed residents may overshadow attending surgeons' perceptions of their innate abilities. These findings demonstrate significant, neuropsychologically based differences among surgery residents that pose unique challenges to persons responsible for their selection and training. PMID- 4035572 TI - Hemodynamic effects of surface cooling-induced hypothermia on immature pigs with ventricular septal defects. AB - Clinical interventions for repair of congenital heart defects, such as hypothermia and cardiopulmonary bypass, may cause changes in pulmonary vascular resistance (PVR) and systemic vascular resistance (SVR) leading to deleterious alterations in blood flow. Since the relationship between the pulmonary and systemic circulations in patients with ventricular septal defects (VSDs) is dynamic and susceptible to stimuli, we directly measured hemodynamic variables and blood flow distribution in infant pigs with VSDs during surface cooling. In 12 piglets (aged 4 weeks and weighing 4 kg), VSDs were created by caval occlusion, right ventriculotomy, and septal perforation, resulting in a 2.2 +/- 0.4:1 shunt. SVR and PVR were derived by both the flow probe (FP) and microsphere (microseconds) techniques. Systemic and pulmonary blood flow distribution were measured (microseconds). Qp/Qs ratios were derived by oximetry, FP, and microseconds techniques. Pigs were surface cooled in 28 degrees C while measurements were made at 37 degrees, 32 degrees, and 28 degrees C. SVR increased by FP (4034 +/- 55.4 to 10450 +/- 2132 dynes-sec/cm5 [p less than 0.05]) and by microseconds (3097 +/- 497 to 1022 +/- 2583 dynes-sec/cm5 [p less than 0.05]), while PVR remained unchanged. Qp/Qs ratios increased during hypothermia by FP (2.4 +/- 0.4:1 to 6.3 +/- 1.4:1 [p less than 0.05]), by microseconds (2.2 +/- 0.4:1 to 3.5 +/- 0.8:1 [p less than 0.05]), and by oximetry (1.4 +/- 0.1:1 to 2.6 +/- 0.3:1 [p less than 0.05]). Visceral flow (34.8 +/- 5 to 17.5 +/- 4 ml/100 gm/min [p less than 0.05]) and renal flow (127 +/- 21 to 53 +/- 11 ml/100 gm/min) [p less than 0.05]) both decreased during hypothermia. Systemic surface cooling induced hypothermia in pigs with VSD causes an increase in SVR but no change in PVR resulting in an increased left to right intracardiac shunt confirmed by three measurement techniques. Redistribution of blood flow favors the lungs while lowering renal and visceral flow. Surface cooling-induced hypothermia and circulatory arrest in infants with VSDs may cause circulatory alterations leading to increased left to right shunt and decreased renal and visceral flow even before cardiopulmonary bypass and intracardiac repair. PMID- 4035573 TI - Histopathologic factors conducive to experimental ventricular tachycardia. AB - Ventricular tachyarrhythmia is the leading cause of sudden cardiac death. Determination of the substrates conducive to the initiation of this arrhythmia remains an important clinical goal. The purpose of this study was to correlate histopathologic findings, specifically: pattern (heterogeneous versus homogeneous infarct morphology), distribution (viable epicardial and/or endocardial rim), and infarct size, with susceptibility to the initiation of sustained ventricular tachycardia employing programmed electrical stimulation in two canine models of experimental myocardial infarction. Twenty-one adult dogs were randomly divided into two groups: 12 dogs underwent two-stage, 2-hour occlusion of the proximal left anterior descending coronary artery and nine animals underwent permanent, complete occlusion of the left anterior descending coronary artery with latex embolization. With programmed ventricular pacing with two premature ventricular extrastimuli, initiation of ventricular tachycardia was attempted, open chest, two weeks after infarction. Electrophysiologic evaluation of the infarct type correlated significantly with the histologic morphology of the infarction (p less than 0.001). The presence of a viable epicardial rim was an extremely important variable for ability to induce sustained ventricular tachycardia (p = 0.04). The presence of an endocardial rim was not significant (p = 1.0). Infarct size alone was only marginally related to ventricular tachycardia inducibility (p = 0.08). Nonuniform infarcts were more conducive to the initiation of sustained ventricular tachycardia than were homogeneous infarcts (p = 0.025). The presence of a large, nonuniform infarct correlated best with inducibility (p = 0.0002). Thus in these experimental models, specific infarct morphologies correlate significantly with susceptibility to inducible sustained ventricular tachyarrhythmias. PMID- 4035574 TI - The role of adenosine in the regulation of coronary blood flow in newborn lambs. AB - Adenosine is a metabolic vasodilator of the coronary vessels in the adult. Whether it plays a similar role in the regulation of coronary blood flow (CBF) in the newborn is not known. We evaluated changes in adenosine release during periods of decreased oxygen supply (hypoxia) and increased oxygen demand (dobutamine infusions). In anesthetized open-chest lambs (age 1 to 8 days), aortic and coronary sinus adenosine concentrations, circumflex CBF, and myocardial oxygen consumption (MVO2) were measured. Adenosine was assayed by high performance liquid chromatography, and the release of adenosine was calculated as the product of the aortic-coronary sinus plasma level difference and CBF in milliliters per minute per 100 gm myocardial tissue. Control values were obtained when the lambs were ventilated with 60% oxygen. In the first series of experiments, hypoxemia resulted in an increase in CBF from 120 +/- 5 to 171 +/- 8 ml/min/100 gm (p less than 0.01). This was associated with sixfold increase in adenosine release. In a second set of experiments the intravenous infusion of dobutamine resulted in parallel increases in MVO2 and CBF. Concomitantly, adenosine release increased by fivefold. There were significant linear relationships between MVO2 and CBF (r = 0.96; p less than 0.01), MVO2 and adenosine release (r = 0.69; p less than 0.002), and adenosine release and CBF (r = 0.71; p less than 0.002). These data support the hypothesis that adenosine may play an important role in the regulation of CBF in the newborn lamb. PMID- 4035575 TI - Quantification of pulsatile flow during cardiopulmonary bypass to permit direct comparison of the effectiveness of various types of "pulsatile" and "nonpulsatile" flow. AB - The relative merits of adding a "pulsatile" component to flow during cardiopulmonary bypass (CPB) has long generated controversy, the resolution of which has been hampered by lack of quantification of the "pulsatility" delivered by different devices. The present experimental series had two goals: to quantify the "pulsatility" of blood flow during CPB in terms of pulse rate and pulsatility index (PI) and to examine which aspects of a "pulsed flow" provide clinical benefits. A flow waveform can be expressed in terms of its baseline rate and its PI, the sum of the square of its harmonics components divided by the square of the mean flow. We used PI to quantify the pulsatility of blood flow in the descending thoracic aorta and used changes in the serum lactate level as an indication of end organ flow. In one experimental series seven adult mongrel dogs were placed on roller pump CPB at a constant flow of 100 ml/kg/min. After a 20 minute stabilization period a roller pump wave and three different pulse shapes (generated by a computer-controlled hydraulic pump) were evaluated for 15 minutes each. The pulse wave shapes were graded, with C being the sharpest and A the least sharp. In a second series six other dogs were placed on CPB and were subjected to roller pump perfusion and three pulse waves of identical shape but at different rates. The results indicated that a combination of a minimum PI of 1.88 and a minimum rate of 80 bpm were necessary to significantly reduce lactate production as compared with roller pump perfusion. Thus the same mean flow can have very different physiologic effects depending on how it is delivered. This quantification method permits direct comparison of different "pulsatile waveforms" and provides a means for identification of optimal pulsatile flow. PMID- 4035576 TI - The pathophysiology of hyperchloremic metabolic acidosis after urinary diversion through intestinal segments. AB - The pathophysiology of hyperchloremic metabolic acidosis after urinary diversion through intestinal segments has not been defined. This study employs a canine model in which an ileal segment is interposed between one kidney and the urinary bladder. Comparison of urinary solute excretion rates between the normal and interposed renal units allows quantitation of solute reabsorption and secretion by the ileal segment. Ileal segments reabsorb urinary chloride, potassium, and ammonium. Ammonium is reabsorbed in part as its conjugate free base, ammonia, with the liberated hydrogen ion reabsorbed with chloride or excreted as titratable acid. Inability to excrete acid as ammonium results in depletion of body buffers and a diminished capacity to compensate an additional acid challenge. Bicarbonate is secreted by the ileal segments but not in amounts that are physiologically significant. Impaired renal function predisposes to the development of this syndrome but is not a primary pathophysiologic mechanism. PMID- 4035577 TI - Temporary banding of the gastroesophageal junction in the critically ill neonate with esophageal atresia and tracheoesophageal fistula. AB - Patients with esophageal atresia and a distal tracheoesophageal fistula with associated conditions contributing to decreased pulmonary compliance present special problems in management. In the face of positive pressure ventilation, the fistula acts as a vent preventing adequate ventilatory effort from reaching the lungs. A thoracic approach to ligate or divide the fistula carries with it a high mortality rate. A technique is described whereby a silicone rubber band is applied to the gastroesophageal junction to effectively occlude the esophagus. It is designed so that is can be adjusted or removed, without operative intervention, according to the patient's clinical course and growth. PMID- 4035578 TI - Angiographic demonstration of mesenteric arterial changes in postcoarctectomy syndrome. AB - A 32-year-old man developed abdominal pain and the paradoxical hypertension after aortic coarctation repair. Abdominal angiography revealed widespread changes of the branches of the superior mesenteric artery and the celiac axis. After the conservative treatment, both the abdominal pain and the angiographic changes disappeared. PMID- 4035579 TI - Aneurysm of persistent sciatic artery: report of a case treated by endovascular occlusion and femoropopliteal bypass. AB - Aneurysmal degeneration is the most serious complication of persistent sciatic artery. In the literature there have been only 16 surgically treated cases. We report one additional case to present an original and safe method of treatment: balloon endovascular occlusion and femoropopliteal bypass. Diagnosis and other methods of treatment are discussed. PMID- 4035580 TI - Varicose ulcer of the upper extremity. AB - Serious complications of local venous hypertension occur rarely in the upper extremity. These are most frequently the result of a dysfunctional arteriovenous fistula and may produce changes indistinguishable from those of chronic lower extremity venous insufficiency. A combination of arterial and venous contrast imaging is essential for identifying major venous outflow obstruction and for planning appropriate surgical therapy. PMID- 4035581 TI - Brain manganese, catecholamine turnover, and the development of startle in rats prenatally exposed to manganese. AB - Manganese (Mn) can be neurotoxic when present in high concentrations. Neonatal animals show differential absorption, accumulation, and excretion of Mn relative to adults. If similar kinetic differences exist during gestation, then fetal animals may be susceptible to Mn neurotoxicity. The objective of this study was to examine maternal-fetal Mn transfer and the susceptibility of prenatal animals to Mn neurotoxicity. This was approached by studying the ability of Mn to cross the placenta and reach the fetal central nervous system using radiotracer and atomic absorption spectroscopy techniques. Manganese is thought to disrupt catecholamine neurotransmission in the central nervous system. This was examined in newborn rats by alpha-methyl-para-tyrosine induced catecholamine turnover and the development of the acoustic startle response. The results suggest that there are limits on fetal Mn accumulation under conditions of both normal and excessive dietary Mn levels. Manganese accumulation in the fetal brain after exposure to increased dietary Mn does not alter either dopamine or norepinephrine turnover or the development of the acoustic startle response. Excess Mn does not appear to be neurotoxic to fetal rats in spite of its limited accumulation in nervous tissue after gestational exposure. PMID- 4035582 TI - Identification of the cellular retinoic acid binding protein (cRABP) within the embryonic mouse (CD-1) limb bud. AB - Retinoic acid, a physiologically active metabolite of vitamin A, is known animal teratogen. Among other malformations, limb abnormalities are produced and are attributed to a selective inhibition of differentiating prechondrogenic mesenchyme resulting in reduced or absent cartilage elements. Evidence is available that the cellular retinoic acid binding protein (cRABP) may be important in mediating the biological effects of retinoic acid. In this study, the cRABP has been identified by sucrose gradient sedimentation analysis in the gestation day 10 (Theiler stages 16-17) mouse forelimb bud, which contains retinoic-acid-sensitive prechondrogenic mesenchyme. Saturation analysis demonstrated values for the apparent dissociation constant (Kd) of 2.0 and 2.2 X 10(-9)M and for the total specific binding capacity for [3H]-trans-retinoic acid of 24.5 and 25.6 pmoles per mg cytosolic protein. The binding specificity of the forelimb bud cRABP for all-trans-retinoic acid was demonstrated in competition assays using all-trans-retinol, all-trans-retinal, and 13-cis-retinoic acid. In addition, 13-cis-retinoic acid was demonstrated to have a lower affinity for the cRABP than all-trans-retinoic acid, a result which may be related to the lower teratogenic potency of the 13-cis-retinoic acid. Thus, the cRABP was demonstrated in the mouse forelimb bud at a time of susceptibility for the production of limb malformations by retinoic acid. The role of the cRABP in the mechanism of retinoic acid teratogenicity remains to be delineated. PMID- 4035583 TI - Effect of ethinyl estradiol on the differentiation of mouse fetal testis. AB - In an evaluation of the effect of ethinyl estradiol (EE) on the differentiation of fetal mouse testes, the ratio of the seminiferous tubular region to the testicular tissue region, the ratio of Sertoli cells to gonocytes in tubule cross sections, and the size of Leydig cells were determined by the Texture Analyse System (T.A.S., Leitz) in histological preparations of the testes. The testes were those of fetuses taken from dams given orally 0, 0.02, 0.2 or 2.0 mg/kg of body weight of EE in olive oil from day 11 through day 17 of gestation and killed at term. From experimental and the control testes, five sections were taken at 40 micron intervals. The areas of the seminiferous tubular region and the testicular region were determined and the Sertoli cells and gonocytes in tubule cross section were counted in each of the five sections. The diameters of 100 Leydig cells selected at random were averaged. These data were analyzed by Student's t test. The seminiferous tubular region was significantly increased in the testes treated with 0.02 mg/kg of EE and significantly decreased in those treated with 0.2 mg/kg of EE. The number of gonocytes per tubule cross section was significantly increased in the testes treated with 0.02 or 2.0 mg/kg of EE. The number of Sertoli cells per tubule cross section and the number of Sertoli cells per gonocyte were significantly decreased in the experimental testes. The size of the Leydig cells was significantly decreased in the testes treated with 0.2 mg/kg of EE. These findings suggest that prenatal exposure to EE before testicular differentiation affects tubular formation, the proliferation of fetal Sertoli cells, and Leydig cell differentiation, resulting in disturbances of spermatogenesis. PMID- 4035584 TI - Effects of dexamethasone on phospholipase activities in palate mesenchyme cells in vitro. AB - Treatment of primary cultures of palate mesenchyme cells from AJAX strain embryos with dexamethasone inhibited only phospholipase activity expressed at pH 7.5. A similar treatment did not have such an effect on palate mesenchyme cells from C57BL/6J strain embryos. Since the AJAX strain embryo is sensitive to the induction of cleft palate by exogenous glucocorticoids and the C57BL/6J strain is less so, these data allow consideration of phospholipase activity as a site of regulation for development of the palate. PMID- 4035585 TI - Genetic analysis of spontaneous and induced palatal slit in C57BL/6 mice. AB - The results of experiments designed to elucidate the nature of the genetic factors underlying the palatal slit defect in C57BL/6 mice indicate that probably two loci in females and four in males determine the difference in susceptibility to the spontaneous defect between the C57BL/6 and SWV/BcTa strains of mice. Moreover, it appears that these are not the same genes determining the difference between these same strains in palatal slit response to maternal treatment with triamcinolone. Additional evidence is presented to support the view that in the C57BL/6 strain the triamcinolone-induced palatal slit and cleft palate responses are not correlated. PMID- 4035586 TI - Goldenhar syndrome, anterior encephalocele, and aqueductal stenosis following fetal primidone exposure. AB - Fetal exposure to primidone was associated with Goldenhar syndrome, hemifacial microsomia, tetralogy of Fallot, aqueductal stenosis, and anterior encephalocele in this male infant. No similar cases in anticonvulsant-exposed pregnancies were found on literature review, despite the increased incidence of other anomalies following such exposure. Goldenhar syndrome, especially related to rare central nervous system anomalies, is reviewed. Experimental production of hemifacial microsomia by a folic acid antagonist, triaxene, is mediated via hemorrhage in the fetus. Intraventricular hemorrhage was noted in this infant as were dilated lateral and third ventricles. The hemorrhagic diathesis and/or the folic acid depletion of newborns following fetal anticonvulsant exposure may have been the underlying mechanism. PMID- 4035587 TI - Teratogen update: clinical aspects of thalidomide embryopathy--a continuing preoccupation. AB - There is much misinformation in the medical community regarding the thalidomide syndrome. Some physicians and scientists are unaware of the fact that organs other than the limbs were frequently affected. Some believe that thalidomide could produce any type of limb reduction defect. Most were aware of the very narrow period of early organogenesis during which the thalidomide-type malformations could be produced. Important features include the fact that limb reduction defects were primarily preaxial, included concomitant girdle hypoplasia when limb reductions were severe, were almost universally bilateral and did not include distal transverse-type defects often called "hemimelia". While it can be said that some spontaneous (non-thalidomide) malformations can mimic the thalidomide syndrome, it can also be said that many limb reduction defects can be determined not to have been produced by thalidomide. The risks of the various defects can be estimated following exposure, with most certainty for limb defects, with less certainty for other defects. Many defects were not associated with exposure to thalidomide such as cleft lip and severe mental retardation. PMID- 4035588 TI - Sauna and birth defects. PMID- 4035589 TI - Teratogenicity of dimethoxyethyl phthalate and its metabolites methoxyethanol and methoxyacetic acid in the rat. AB - It is hypothesized that the known teratogen di(2-methoxyethyl) phthalate (DMEP) acts by in vivo hydrolysis to 2-methoxyethanol (2-ME), also a known teratogen, which in turn is metabolized to methoxyacetic acid (MAA), the proximate teratogen. Teratological studies were conducted with Wistar rats, with the administration of these three agents on day 12 of gestation. On an equimolar dosage basis, DMEP, 2-ME, and MAA were equally potent, which is consistent with the hypothesis. There was a striking similarity in the defects produced by these agents, mainly hydronephrosis, heart defects, and short limbs and tails. In particular all three agents produced unusual heart defects (dilated ductus arteriosus and dilated aortic arch) not seen with other agents, as well as ventral polydactyly, a rarely seen defect, suggesting teratogenic action by a common mechanism or component; 4-methylpyrazole, an alcohol dehydrogenase inhibitor, provided significant protection against 2-ME. This combination of effects strongly suggests that following the administration of DMEP, 2-ME, or MAA, MAA is the proximate teratogen. PMID- 4035590 TI - Electrocardiographic study of rat fetuses exposed to ethylene glycol monomethyl ether (EGME). AB - The widely used industrial solvent ethylene glycol monomethyl ether (EGME) is teratogenic to rats and mice, inducing a variety of heart and major vessel abnormalities. In the present study, electrocardiography was used to evaluate heart function in day 20 rat (Sprague-Dawley) fetuses from mothers treated on gestation days 7-13 (sperm = day 1) with 0, 25, or 50 mg/kg EGME by gavage in 10 ml/kg water. The increased incidence of fetuses with cardiovascular malformations (primarily right ductus arteriosus and ventricular septal defect) and abnormal electrocardiograms (EKG) was dose dependent. The most prevalent EKG abnormality was a prolonged QRS wave. Mean QRS intervals were not significantly increased by EGME exposure, but there were significantly more litters in the 50-mg/kg EGME group that had one or more fetuses with QRS complexes of 40 msec or longer. The enhanced duration and the appearance of the aberrant QRS's suggested the presence of an intraventricular conduction delay in these fetuses. Heart rate and other EKG characteristics such as the P wave or P-R and Q-T intervals were not significantly affected by exposure to EGME. There did not appear to be an association between abnormal EKG's and fetal heart dysmorphology. PMID- 4035591 TI - Maternal factors in congenital limb-reduction defects. AB - Various maternal characteristics were examined in case-control studies of limb reduction defects among live births in Upstate New York (i.e., New York State exclusive of New York City). In a study using birth records of 305 cases and 915 controls born in 1970-81, mean birth weight and gestation length were significantly lower in cases than in controls, and certain pregnancy complications (i.e., abnormal vaginal bleeding and diabetes mellitus) were reported more often in cases than in controls. Several subgroups of defects (i.e., isolated defects vs. multiple, long-bone defects vs. other) were also compared with their respective controls. The subgroup with multiple (including nonskeletal) defects had the lowest mean birth weight and length of gestation. In an interview study of 108 cases and 108 controls born in 1968-74, a history of maternal use of thyroid medication was a significant risk factor; possible explanations for this association are discussed. PMID- 4035592 TI - Induction of chick embryo feather malformations by an influenza C virus. AB - The effect of influenza C virus, strain JJ/50, on the development of chicken embryos infected at 10 or 12 days was documented by microscopic techniques, as well as by gross observations of embryos or chicks at hatching. The infected, newly hatched chicks displayed marked abnormalities in their feathering. Such abnormalities were observed neither in mock-infected embryos nor in embryos injected with virus which had been previously treated with specific influenza C virus antibody. At a microscopic level, the abnormalities apparently are a result of hypertrophy and/or hyperplasia of the developing barb and barbule cells. Further, the additional development of integumental necrotic foci was correlated with the development of relatively high viral titers (greater than 256) as measured by hemagglutination (HA). Embryos infected after 12 instead of 10 days incubation showed normal feathering at hatching. Infection at 12 days, however, was correlated with the development of relatively low viral titers (HA = 4) and limited degeneration of the respiratory epithelium. The relationship of teratogenic effects to the site of viral replication in rapidly differentiating tissue is discussed. PMID- 4035594 TI - Prevention of the eye closure defect in lgMl/lgMl fetal mice by thyroxine. AB - The open-eye birth defect of mice caused by the lgMl mutation was prevented by prenatal administration of thyroxine (T4) to the pregnant mother. Treatment on days 10 to 11 of gestation was most effective in preventing open-eyes. A contrasting worsening of the defect was seen after treatment on day 14 of gestation. A dose-response relationship for prevention appeared to be present up to a dose of 0.1 mg/mouse, after which 39% of fetuses had both eyes closed compared to 2% in controls. Higher doses appeared to give little or no further increase in beneficial effect. Scanning electron microscopy was used to compare thyroxine-treated and untreated lgMl/lgMl and normal CBA/J day 16 or 17 fetal eyes. Mutant eye closure after thyroxine differed from untreated mutant in the growth of both upper and lower eyelids across the eye and in increased numbers of rounded periderm cells on the advancing lid edges. The underlying epithelial tissue layer appeared to fuse closed. The induced eye closure in the mutant was not normal, however. The periderm cell layer had disorderly fusion at the outer canthus, premature flattening, and failure to fuse in the inner canthus. PMID- 4035593 TI - Teratogenicity and embryolethality of acrolein and structurally related compounds in rats. AB - Acrolein, a metabolite of the anticancer agent cyclophosphamide, is teratogenic to rats after intraamniotic administration. It is not known whether acrolein or a metabolite of acrolein is responsible for the teratogenicity of this compound. We assessed the teratogenicity and embryolethality of acrolein and five structurally related compounds: acrylic acid, allyl alcohol, glycidol, glyceraldehyde, and propionaldehyde by intraamniotic injections in Sprague-Dawley rats on day 13 of gestation. All compounds tested were significantly embryolethal with at least one concentration of the drug. Acrolein was the most embryolethal of the drugs, causing a significant increase in resorptions with as little as 0.1 micrograms/fetus; the other drugs were embryolethal at doses 100-10,000 times that of acrolein. Acrolein was also the most teratogenic of the drugs tested; a dose as low as 5 micrograms/fetus caused a significant increase in the incidence of fetal malformations. Of the other compounds tested, only glycidol at a dose of 1,000 micrograms/fetus induced a significant number of malformed fetuses compared to control. These results suggest that it is acrolein itself that is responsible for its teratogenicity. PMID- 4035595 TI - Granulomatous disease complicating hairy cell leukemia. PMID- 4035596 TI - Frequency of preparticipation sports examinations in secondary school athletes: are the University Interscholastic League guidelines appropriate? PMID- 4035597 TI - Predictors of nursing home placement of patients with Alzheimer's disease. PMID- 4035598 TI - Catheter size and rapid crystalloid infusion. PMID- 4035599 TI - Psychotic reactions to a natural disaster: Hurricane Alicia. PMID- 4035600 TI - Contractual arrangements between lay corporations and physicians--patient safeguards. PMID- 4035601 TI - Indications for bone marrow examination. PMID- 4035602 TI - Suicide by adolescents. PMID- 4035604 TI - Ten steps to the courthouse. PMID- 4035603 TI - Texas EMS--policies and people. PMID- 4035605 TI - Contractual arrangements between lay corporations and physicians--patient safeguards--Part II. PMID- 4035606 TI - Disease and the humanities. PMID- 4035607 TI - Cancer and the development of will. PMID- 4035609 TI - Health and life. PMID- 4035608 TI - Scepticism and public health: on the problem of disease for the collective. PMID- 4035610 TI - Remarks in praise of guilt. PMID- 4035611 TI - The language of pain. PMID- 4035612 TI - Disease and social theory: a problem of conversation. PMID- 4035613 TI - Construction of illness: deconstructing the social. PMID- 4035614 TI - Ultrastructural organisation of intraepithelial nerves in the human airway tract. AB - Intraepithelial nerves of human airway tract were studied by electron microscopy after conventional glutaraldehyde fixation. Specimens were obtained from five patients at three different airway levels--the trachea, the right upper lobe bronchus, and segmental bronchus. Intraepithelial axon profiles were located either near the basement membrane or close to the lumen but were rare in the intermediate area of the epithelium. Axon profiles close to the lumen were seen only in the central airways (levels 1 and 2), while profiles close to the basement membrane were seen in all three levels. PMID- 4035615 TI - Transepithelial potential difference in cystic fibrosis. AB - In cystic fibrosis the potential difference between interstitial fluid and the surface of respiratory and sweat duct epithelia is abnormally large. This study attempted to confirm this finding and investigate its value for a diagnostic test. With a subcutaneous reference electrode the mean potential difference of the inferior turbinate was -25 mv in 19 patients with cystic fibrosis, which was significantly greater than the difference of -13 mv in 22 normal subjects (p less than 0.02). Of the observations in the patients with cystic fibrosis, 67% were greater than the largest potential difference observed in normal individuals. Potential differences from the lip and forearm were also significantly greater in cystic fibrosis than in normal subjects, but there was considerable overlap. Changes in the electrical properties of nasal epithelium and skin have been confirmed in cystic fibrosis, but these have limited use for diagnosis. PMID- 4035616 TI - Chronic pulmonary sarcoidosis: relationship between lung lavage cell counts, chest radiograph, and results of standard lung function tests. AB - Thirty three consecutive untreated patients with pulmonary sarcoidosis, confirmed histologically or by Kveim test, were investigated to correlate cell counts in bronchoalveolar lavage fluid with clinical features, the chest radiograph, and results of lung function tests. A persistently abnormal radiograph had been observed for one year or more in 26 (79%) and for two years or more in 20 (61%), but only 24% had dyspnoea. Twenty (61%) of 33 patients showed an increased percentage of lymphocytes in bronchoalveolar lavage fluid, although only eight (24%) exceeded 28%. A moderate increase of neutrophils, up to 12%, was found in 14 (42%). Lymphocyte percentage counts were higher in the group of patients without evidence of radiographic contraction suggesting fibrosis, and this contrasted with higher percentage neutrophil counts in those with contraction. There was also a correlation between the percentages of neutrophils and increasing radiographic profusion scores (p less than 0.001), suggesting that neutrophils may reflect the severity of the parenchymal legions as well as fibrotic distortion, and an inverse correlation with vital capacity (p less than 0.001) and transfer factor (TLCO) (p less than 0.1 greater than 0.05). No significant correlation was found between the lymphocyte counts and radiographic profusion scores, vital capacity or TLCO; but it was noted that all eight patients with high lymphocyte counts (greater than 28%) had radiographic profusion scores less than 12. This study shows that, especially in sarcoidosis with more extensive radiographic shadows of long duration, bronchoalveolar lavage neutrophils may be important as well as lymphocytes in clinical assessment of "activity" of disease. These observations are important because they throw doubt on whether the lavage lymphocyte count alone can be used as an indicator of the need to start corticosteroid treatment. PMID- 4035617 TI - Asbestosis: assessment by bronchoalveolar lavage and measurement of pulmonary epithelial permeability. AB - Thirty two patients with asbestosis were assessed by means of bronchoalveolar lavage (27 patients) and the half time clearance from lungs to blood (T1/2LB) of an inhaled aerosol of diethylenetriamine pentacetate (DTPA) labelled with technetium 99m (32 patients). T1/2LB was also measured in 20 non-smoking normal individuals and 17 smokers without a history of exposure to asbestos. Thirteen patients (46%) showed an increase in the percentage of neutrophils with or without an increase in the percentage of eosinophils and eight (29%) showed an increased percentage of lymphocytes. The number of neutrophils plus eosinophils expressed as a percentage of the total count was positively correlated with the length of the history of disease (r = 0.53, p less than 0.025) and greater percentages were associated with more severe impairment of lung function. Smokers had lower percentages of lymphocytes than non-smokers (p less than 0.002) and showed increased proportions of neutrophils and eosinophils more often than non smokers (p less than 0.05). In 18 non-smokers with asbestosis the mean T1/2LB was 33.8 (range 10.0-62.0) minutes, significantly less than 57.2 (30.5-109) minutes in 20 non-smoking normal subjects (p less than 0.002). In non-smokers shorter T1/2LB correlated with a longer time since first exposure to asbestos (r = -0.65, p less than 0.005), longer duration of exposure (r = -0.70, p less than 0.001), and a shorter time since last exposure (r = 0.59, p less than 0.01). Shorter T1/2LB was also associated with increased inflammatory activity as shown by higher bronchoalveolar lavage cell counts (r = -0.53, p less than 0.025) and higher combined percentages of neutrophils, eosinophils, and lymphocytes (r = 0.47, p less than 0.05). The techniques of bronchoalveolar lavage and measurement of inhaled solute clearance may be useful in assessing inflammatory activity in asbestosis. PMID- 4035618 TI - Further experience of Corynebacterium parvum in malignant pleural effusion. AB - The outcome of drug induced pleurodesis has been evaluated in a non-randomised retrospective study of 67 patients with recurrent malignant pleural effusions treated during 1976-83. Fourteen died within 30 days of treatment. Of the remaining 53 patients, 26 studied during 1976-80 were treated with intrapleural mustine hydrochloride, while 27 studied during 1978-83 were treated with intrapleural Corynebacterium parvum. There was no significant difference between the groups in age, sex, or tumour type, most tumours being secondary to bronchial neoplasms. Corynebacterium parvum successfully prevented reaccumulation of the effusion in 24 (92%) patients, while mustine was effective in only 17 (65%) (p less than 0.05). Data on survival were obtained on 47 cases where a single agent was used to induce pleurodesis. In 25 patients treated with C parvum the mean survival was 251 (range 31-1143) days, compared with 119 (range 31-380) days for the 22 patients in whom mustine was used. Survival of the C parvum group was significantly greater (p less than 0.01). The difference was principally due to the greater number of long term survivors in the C parvum group, nine of this group living for more than 180 days (mean 574, range 180-1143 days) compared with only four such survivors in the mustine group (mean 263, range 193-380 days). This study confirms our initial impression that C parvum is highly effective in controlling recurrent malignant pleural effusions. The finding of unexpected long term survivors with C parvum treatment suggests that this treatment may have an additional effect on the progression of disease, a finding that merits further investigation. PMID- 4035619 TI - Relationship between saliva and free and total plasma theophylline concentrations in patients with chronic airflow obstruction. AB - Total plasma and mixed stimulated saliva theophylline concentrations (by high performance liquid chromatography) and free plasma theophylline concentrations (by equilibrium dialysis) were measured in simultaneously collected samples from 32 outpatients receiving chronic oral theophylline treatment, who had received the drug at least two hours before sampling. There was a close relationship between saliva and total plasma theophylline concentration and between total saliva and free plasma concentration. The mean saliva to total plasma drug concentration ratio was 0.69 (SE 0.09) and the mean difference between paired saliva and free plasma concentration was 0.65 (0.17) microgram/ml. It is concluded that stimulated mixed saliva provides a simple, non-invasive method of assessing total (and free) plasma theophylline concentrations during chronic oral treatment. The therapeutic range for saliva, corresponding to the generally accepted total plasma concentration range (10-20 micrograms/ml), is approximately 7-14 micrograms/ml. PMID- 4035620 TI - Clinical and radiographic features of psittacosis infection. AB - Forty three cases of psittacosis infection were identified retrospectively over a five year period. The commonest clinical presentation was of a bronchitic illness with a productive cough and features of systemic upset. In 12 (28%) cases no radiographic abnormality was detected on the chest film. Segmental shadowing was the commonest abnormality but lobar and more extensive consolidation occurred. There were no radiographic features that allowed confident differentiation from other causes of pneumonia. The total and differential white cell counts were usually normal and this feature may help to differentiate psittacosis from bacterial pneumonia. PMID- 4035622 TI - Amyloidosis of the respiratory tract treated by laser therapy. PMID- 4035621 TI - Ligation of patent ductus arteriosus in very low birthweight premature neonates. AB - The results of ligation of a patent ductus arteriosus in 30 premature neonates with a very low birth weight were analysed. The mean gestational age at birth was 27 weeks and the mean weight 811 g. Attempted closure of the ductus with indomethacin in 19 infants failed, though there was temporary closure in nine. Congestive heart failure was present in 29 and respiratory distress in 22 patients. Endotracheal intubation with assisted ventilation was necessary in all cases. The mean age at operation was 13.5 days and ductal ligation was performed in the intensive care unit under local anaesthesia supplemented with pancuronium and pethidine. There were no intraoperative deaths, but five infants died in hospital. There were seven late deaths. Eighteen survivors have been followed for a mean of 26.5 months. Early ligation of a patent ductus arteriosus in premature infants with a very low birth weight improved the cardiorespiratory state. Long term follow up showed good clinical progress in two thirds of the surviving group. PMID- 4035623 TI - Secondary bacterial infections in children with proved Mycoplasma pneumoniae. PMID- 4035624 TI - Primary pleural liposarcoma. PMID- 4035625 TI - Chest injury complicated by shock induced necrosis of the colon. PMID- 4035626 TI - Spontaneous intramural oesophageal dissection. PMID- 4035627 TI - Asthma due to contaminated humidifiers. PMID- 4035628 TI - Performance, ventilation, and oxygen consumption in three different types of exercise test in patients with chronic obstructive lung disease. AB - Seventeen patients (six men and 11 women, mean age 66 years) with severe chronic obstructive lung disease (mean FEV1 0.8 (SD 0.3)1) performed three different types of exercise test on four occasions within one week. Three daily doses of placebo tablets were given between the third and fourth attempt at each test. The tests were the 12 minute walking test, a fixed rate and height paced step test, and a cycle ergometer test in which the work rate was increased by 10 watts each minute. Performance increased significantly (p less than 0.01) between the first and fourth attempts in each type of test (12 min walking distance 16% (SD 20%); steps climbed 96% (74%); duration of cycling 29% (41%]. There was a trend for the increase in performance between successive attempts to become progressively smaller but this was not significant. No effect of placebo on exercise performance was detected. The greatest intersubject range of performance was seen in the step test (14-126 steps) and the least in the walking test (438-1014 m). Significant correlations (p less than 0.01) were observed between performance in all three types of exercise test, but the correlations found between the results of the various tests of exercise performance and the FEV1 and the FVC were either weak (p less than 0.05) or non-significant. Ventilation (VE) and oxygen consumption (VO2) were subsequently measured and compared in eight patients during all three types of exercise test. Both the VE and the VO2 that were achieved in the step test were significantly greater than in either the cycle or the walking test. No patient was able to reach and sustain steady state values of VE and VO2 in the step test, whereas a steady state for both VE and VO2 was reached and sustained by all eight patients in the walking test. It is suggested that at least three practice attempts at any exercise test should be made before the introduction of either placebo or specific pharmacological treatment and that even then it may be necessary to allow for the effects of further repeated testing in the assessment of the results of treatment. PMID- 4035629 TI - Gastro-oesophageal reflux and childhood asthma: the acid test. AB - The presence of gastro-oesophageal reflux was investigated in 18 children with moderate to severe asthma by overnight oesophageal pH monitoring. Appreciable reflux was found during sleep in eight; its relevance to nocturnal asthma was not clear. On another occasion the same children were challenged in a double blind fashion with a drink of dilute hydrochloric acid (0.001 N) and the response of the airways was monitored by peak flow measurements and by histamine challenge tests. There was a significant increase in mean histamine sensitivity (p = 0.001) 90 minutes after the acid drink without any associated change in baseline peak flow rate. Eight children had a significant response to the acid drink, and a further three reacted to a more concentrated solution (0.01 N). In those asthmatic children in whom reflux is associated with a positive response to an acid drink (five out of 18 in the present study) it seems likely that reflux exacerbates nocturnal symptoms. PMID- 4035630 TI - Bronchial hyperreactivity to histamine in aspirin sensitive asthmatics: relationship to aspirin threshold and effect of aspirin desensitisation. AB - Twenty seven aspirin sensitive asthmatic patients were studied to determine the relationship between non-specific bronchial responsiveness to inhaled histamine and the degree of sensitivity to aspirin (aspirin threshold dose). No correlation was found between provocative concentration of histamine (PC20H) and aspirin threshold dose. In 11 patients the influence of aspirin desensitisation on bronchial reactivity to inhaled histamine was examined. Mean PC20H measured the day after the patients were desensitised to 600 mg of aspirin did not change significantly from the values before desensitisation. These observations suggest that sensitivity to aspirin and non-specific bronchial hyperreactivity in asthmatic patients are independent phenomena. PMID- 4035631 TI - Effects of histamine on lung permeability in normal and asthmatic subjects. AB - The permeability of respiratory mucosa, as measured by clearance of diethylenetriamine penta-acetate (DTPA) labelled with technetium 99m, was similar in seven normal and nine asthmatic subjects. Histamine induced bronchoconstriction was associated with a 50% increase in permeability in both groups of subjects. In normal subjects inhaled salbutamol, given as 1 mg acutely or as 200 micrograms four times daily for two weeks, had no effect on pulmonary permeability. Salbutamol, given before histamine challenge, prevented bronchoconstriction, but did not affect the increase in permeability seen in normal subjects. Low doses of histamine, sufficient to cause bronchoconstriction in the asthmatic subjects, produced little bronchoconstriction in normal subjects but caused increases in lung permeability similar to those seen in asthmatic subjects. These studies suggest that these two effects of inhaled histamine, bronchoconstriction and increased permeability, are independent. PMID- 4035632 TI - Contribution of the rib cage to breathing in tetraplegia. AB - In tetraplegia there is often paradoxical inward motion of the rib cage during inspiration. The volume of this negative contribution is difficult to estimate but can be obtained by optical mapping. The partitioning of ventilation between the rib cage and abdomen in six normal subjects, 10 stable tetraplegic patients, and one tetraplegic patient at intervals during rehabilitation has been studied by this technique. In normal subjects the tidal volume and the vital capacity were the sum of positive contributions from the rib cage and abdomen. In stable tetraplegic subjects with similar neurological levels, the rib cage contribution varied widely but the total chest wall displacement could not be predicted from the vital capacity. In the patient studied sequentially rib cage paradox reversed with time after injury, and this was associated with an absolute increase in vital capacity and an improvement in the action of the diaphragm. PMID- 4035633 TI - Variable anatomy of the right coronary artery supply to the left ventricle. AB - The right coronary artery is "dominant" (contributing to the supply of the left ventricular muscle) in 90% of people. Although the most common pattern is for the right coronary artery to bifurcate at the crux giving the posterior descending (posterior interventricular) artery, a branch may arise before the crux, either as an aberrant acute marginal artery or as an early posterior descending artery, crossing the diaphragmatic surface of the right ventricle. Recognition of this possibility may be important if surgical revascularisation is to be complete. To establish the frequency of these different patterns of blood supply, 22 hearts were studied in the dissecting room, and 100 consecutive coronary angiograms and 100 consecutive operative drawings were reviewed. A vessel arising before the crux contributed to the supply of the left ventricle in one third of cases. PMID- 4035634 TI - Endocardectomy for the surgical treatment of endocardial fibrosis of the left ventricle. AB - Two patients with endomyocardial fibrosis of the left ventricle were treated by endocardectomy plus mitral valve replacement. In both cases the results of surgery were satisfactory. No consequences related to eosinophilia, which was present before operation in one of them, were noted. The poor prognosis of this progressive disease and the inefficiency of medical treatment compared with the good surgical results already reported from various centres encourage early operation for all patients with endomyocardial fibrosis who have symptoms. Because of the pathophysiology of the disease, endocardectomy should be attempted in all cases and anti-coagulant treatment continued for life. PMID- 4035635 TI - Streptococcus milleri as a cause of pleural empyema. AB - Review of an annual series of cases of empyema seen at a regional cardiothoracic unit showed that six out of 25 were due to Streptococcus milleri. The details of the cases are summarised. This organism is now an important cause of empyema, occurring much more commonly in men than in women; but since it is highly sensitive to penicillins permanent resolution can be achieved with antibiotic treatment combined with open or closed drainage. PMID- 4035636 TI - Monoclonal gammopathies in chest disease. PMID- 4035637 TI - Bilateral diaphragm weakness. PMID- 4035638 TI - Severe diaphragm weakness in multiple sclerosis. PMID- 4035639 TI - Neuralgic amyotrophy with bilateral diaphragmatic palsy. PMID- 4035640 TI - Intralobar pulmonary sequestration of ectopic pancreatic tissue with gastropancreatic duplication. PMID- 4035641 TI - Newly diagnosed cystic fibrosis in middle and later life. PMID- 4035642 TI - Serum concentrations of vitamin D metabolites in untreated tuberculosis. PMID- 4035644 TI - Fibrinolytic activity in thrombin-infused rabbits. PMID- 4035643 TI - Activation of fibrinolysis by apolipoproteins of high density lipoproteins in man. AB - The effects on fibrinolysis of purified normal human plasma lipoproteins and their apolipoproteins (apo) were assessed in an in vitro system containing urokinase, plasminogen, and fibrin. High and very low density lipoproteins (HDL and VLDL, respectively) but not low density lipoproteins (LDL) significantly increased lysis of radiolabeled fibrin or lysis area of plated fibrin compared to controls. Apo HDL, apo HDL2, apo HDL3, apo VLDL (buffer soluble apo), apo AI and AII activated fibrinolysis by 1.3-1.4 fold of control values, whereas apo B (as a narrow density cut of LDL) and non-lipoprotein control proteins (albumin and myoglobin) did not. Addition of HDL in the absence of urokinase failed to activate fibrin lysis. These data demonstrate that the major proteins of HDL - apo AI and apo AII - and possibly certain minor constituent(s) common to HDL and VLDL participate in the fibrinolytic process. PMID- 4035646 TI - The role of the carbohydrate moiety for the inhibitory activity of antithrombin III. PMID- 4035645 TI - In vivo recovery of antithrombin concentrates. PMID- 4035647 TI - Antithrombotic and thrombolytic effects of galactan polysulfate (DH 6322) in rats. AB - Anticoagulant, fibrinolytic and thrombolytic effects of galactan polysulfate (DH 6322), a new semi-synthetic polysaccharide sulfate of bacterial origin, were studied in the rat in vitro, ex vivo and in vivo. Addition of DH 6322 to citrated plasma gave a 50% reduction in euglobulin lysis time at around 50 micrograms/ml and a 2-fold prolongation in plasma recalcification time at 40 micrograms/ml. Intravenous injection of DH 6322 caused significant acceleration of euglobulin clot lysis and urokinase-induced plasma clot lysis at doses as low as 2 mg/kg, and also significant prolongation of plasma recalcification time. Oral application of the compound gave similar effects only at an extremely high dose of 3 g/kg. When injected intravenously before induction of pulmonary thrombosis by lactic acid infusion, DH 6322 was found to be effective in preventing thrombus formation. In progressive venous thrombosis induced by insertion of a steel coil into the inferior vena cava, DH 6322 treatment also caused a significant reduction of thrombus size together with increase in the serum levels of fibrin degradation products. The findings indicate that the antithrombotic effects of DH 6322 result from its enhancement of the fibrinolytic potential as well as its anticoagulative action. PMID- 4035648 TI - Platelet thrombospondin haemagglutinin activity is due to aggregate formation. AB - Thrombospondin released from human blood platelets by thrombin activation formed high molecular weight aggregates which co-eluted with haemagglutinin activity on Sepharose 4B gel filtration. Thrombospondin aggregation was mediated by intermolecular disulphide bridges. The aggregates consisted of a series of oligomers ranging from a dimer to polymeric forms with Mr congruent to 40 X 10(6). Native monomeric thrombospondin obtained by a modified procedure was deficient in haemagglutination activity but inhibited haemagglutination induced by aggregated thrombospondin. PMID- 4035649 TI - Coagulopoietin activity in rat plasma: influence of degree of hypoprothrombinemia and reproducibility of the response. AB - Injection of plasma from a vitamin K-deficient hypoprothrombinemic rat into a normal rat causes an increase in plasma prothrombin activity in the recipient rat. Maximum concentrations of the factor responsible for this response (coagulopoietin) are present in the plasma of rats fed a vitamin K-deficient diet for 7 days and do not increase as the period of deficiency is increased. The coagulopoietin activity of plasma from individual rats is variable, but similar activity was observed when multiple recipient rats received the same donor plasma. PMID- 4035650 TI - Substitution of antithrombin III in shock and DIC: a randomized study. AB - In 51 shock patients with DIC Antithrombin III (AT III) substitution, heparin or a combination of both substances respectively was administered. In the two groups which had been given AT III substitution the concentration of AT III rose considerably higher than the activity. There was a drop of the platelet count in both groups which had received heparin. C1 esterase inhibitor was diminished in the beginning but spontaneously increased in all groups. This increase was slowest in the group without substitution of AT III. The blood loss in cases of traumatic shock was considerably higher in the group which had received both substances. The consumption of AT III concentrates was slightly higher in the combined therapy group than in the AT III group. The duration of symptoms of DIC was considerably shorter in the two substituted groups than in the heparin group. It is concluded that additional administration of heparin does not improve the effect of AT III substitution in patients with DIC and that side effects such as thrombocytopenia and an increased blood loss are likely to develop when both substances are given simultaneously. PMID- 4035651 TI - Fibrinolytic action of a new semi-synthetic polysaccharide sulfate, galactan polysulfate (DH 6322), in the rat. AB - Galactan polysulfate, DH 6322, when added to rat plasma, shortened euglobulin clot lysis time through both increase in the recovery of plasminogen activator activity in euglobulin precipitates and direct acceleration of fibrinolysis. DH 6322 treatment also resulted in accelerating plasma clot lysis induced by urokinase. The effect of DH 6322 was further studied with a purified system composed of bovine fibrinogen and plasminogen. In this system, DH 6322 was found to be a potent stimulator of both fibrinolysis and fibrinogenolysis induced by urokinase. The activation process of plasminogen was not affected by DH 6322 even in the presence of fibrin or fibrinogen. The accelerating effect of DH 6322 on fibrinolysis in the purified system was scarcely affected by addition of plasma antifibrinolytic factors. DH 6322 also stimulated fibrin clot lysis induced by a low concentration of purified plasmin in place of plasminogen and urokinase, and its accelerating effect was not observed in the presence of tranexamic acid. Formation of fibrin clot susceptible to generated plasmin was observed at relatively high concentrations of DH 6322 above 80 micrograms/ml. Additional experiments indicated that DH 6322 increased the amount of plasminogen bound to fibrin. These results suggested that DH 6322 stimulated fibrinolysis through increasing the binding of plasminogen or plasmin to fibrin. PMID- 4035652 TI - Precipitation of fibrinogen, fibrinogen degradation products and fibrin monomer by histone H3. AB - Incubation of histone H3 with normal citrated plasma resulted in the formation of insoluble aggregates, as determined by turbidity measurements. The precipitate was subjected to sodium dodecyl sulfate polyacrylamide gel electrophoresis, confirming that fibrinogen was a major component. Purified fibrinogen precipitated rapidly as determined with turbidity experiments and experiments with radioiodinated protein. The amount of fibrinogen precipitation was strongly dependent on H3 concentration. Variation of ionic strength (0.2-0.84) and pH (5.3 7.4), however, had little or no effect on the reaction. Fibrinogen subjected to gelatin-Sepharose chromatography or dialysis against 3.3M urea reacted equivalently with H3. Precipitation of 125I-fibrinogen by H3 was strongly favored by increasing temperature (4 degrees-45 degrees C). Precipitation of fibrinogen by protamine was maximized by decreasing the temperature. In addition, formation of insoluble fibrinogen-protamine aggregates was highly dependent on ionic strength and pH, suggesting that different types of protein-interaction are involved in the two studied precipitation reactions. Of the fibrinogen degradation products, only fragment X precipitated significantly when incubated with H3. Radioiodinated fibrin monomer also precipitated when incubated with H3 in solutions of sufficient ionic strength to prevent spontaneous polymerization. The extent of precipitation was equivalent for fibrin monomer and fibrinogen. Fragment D inhibited the precipitation of fibrinogen by H3 or protamine. These studies indicate that the proteins termed "paracoagulants" are not all equivalent and that the hydrophobic domain of H3 plays a critical role in fibrinogen precipitation. PMID- 4035653 TI - [Zootechnical procedures for the prevention of paratuberculosis on cattle farms. I. Survey]. AB - A questionnaire which can be used in making an inventory of zootechnic procedures to prevent Johne's disease on infected farms was described in the present paper. The most important rule in prevention by zootechnical measures is to keep the animals from coming into oral contact with the faeces. The background to the various problems were discussed in greater detail. This questionnaire will make possible a systematic approach to and the uniform laying down of zootechnical measures to prevent the transmission of Johne's disease, and may serve as a guide to veterinarians in preventive herd health programmes. PMID- 4035654 TI - [Zootechnical procedures in the prevention of paratuberculosis on cattle farms. II. Analysis]. AB - The present paper is an analysis of the zootechnical procedures adopted to prevent further distribution of infection on twenty-seven farms on which the animals were affected with Johne's disease. This analysis was based on an extensive questionnaire. Housing was not such on any of these farms that spreading of the faeces among the various age groups was ruled out. The designers failed to take the veterinary aspects into account in construction and arrangement of the shelters. The transmission of Johne's disease was possibly promoted by furnishing the shelters with a scraper system to remove the dung, which system also reached the compartment housing young cattle. Preventive procedures in the field of management were not carried out consistently on any of these farms. This was promoted by inadequate advice to stock farmers. These facts should be taken into account in the control of Johne's disease, as part of the preventive measures cannot be directly influenced by livestock farmers in these conditions. PMID- 4035655 TI - [Inclusion hepatitis in 'young' pigeons]. PMID- 4035656 TI - [A case of aldicarb poisoning in cattle]. AB - Six cows fell ill and two died following the spilling of an amount of the pesticide Temik on a pasture. Chemical analyses for aldicarb, the active principle of Temik, in the rumen of a dead animal, showed that a lethal dose of aldicarb was present. Examination for residues resulted in the decision to regard meat and organs as unfit human consumption. From the point of view of prevention of general risks, the milk produced on the day on which the accident was recorded, as well as that produced during the following six days had to be destroyed. PMID- 4035657 TI - [Screening for hearing disorders. Current status and bottlenecks]. AB - In The Netherlands a nation-wide screening program on hearing for infants is available. This program started around the late sixties and is now incorporated in the Health Care System and added to the tasks of the Well Baby Clinics. A modification of the method as developed by the Ewings is used. This method is relatively easy to learn. It is, however, essential that it is executed accurately and with a maximum of care. Therefore the testing itself as well as the assessment of the results is strictly standardized and a lot of attention is given to the training program. The Dutch Foundation for the Deaf and Hearing Impaired Child co-ordinates the screening program. About 75% of the 9 months old babies are screened and some 5% of the children has to be referred. The Ewing test has proved to be effective. It detects both severe and moderate sensory neural hearing-losses as well as conductive hearing-losses. However, the program faces us with a few difficulties: the structure is effective, though time consuming; the referral-procedure is not always satisfactory. Due to different factors, some groups of children, sometimes at risk, are not covered by the screening program or any other program. PMID- 4035658 TI - [Early diagnosis of vision disorders]. AB - In recent years some pilot-studies were performed at health centres in Amsterdam, on infants of 8-9 months of age, concerning early detection of visual disorders. The method consisted of a programme of corneal light reflexes, cover test, monocular following movements and inspection of the cornea, the pupil and the pupillary reaction. The aim of the studies was: 1. Is this programme efficient for early detection of organic eye disorders and strabismus at this age? 2. Is the method reliable, if performed by doctors of the health centres? The results of the studies were positive. In at least 1,9% of the 1200 children of the pilot study a visual disorder was detected. The method can be incorporated in the regular working scheme of the health centres and can be performed on infants from the age of 6 1/2 months. PMID- 4035659 TI - [The medical record in Child Health Services]. AB - The main objective of youth health care is to promote health as well as development in interaction with environmental factors (material and immaterial). Therefore it has a longitudinal character; medical registration ought to be in accordance with this. In this paper a number of examples is given of how youth health care has given shape to a longitudinal design of medical records in the last ten years. PMID- 4035660 TI - [Preventive screening in Child Health Services]. AB - Early detection in the framework of secondary prevention is an important task, although not the only one, of youth health care, 'the preventive and socio medical complement of curative medicine'. The primary aim of youth health care is 'promoting and protecting health, growth and development of children and youths'. Periodic health examinations (PHE'S) are an effective and efficient mean to this end. Like all medical consultations PHE is characterised by the integration of its two components: the analysis which focuses on the individual child and its environment (history and physical examination) and the synthesis (general health education and specific counseling). Moreover PHE provides the basis for epidemiological research, collective health education and policy-planning. Complementary examination of a child, usually less extensive than PHE, is executed on the basis of an individual indication. For practical reasons groups of children may be examined in screening-programs. It is preferable to incorporate screening results in the total medical assessment, which is the result of a series of individual PHE'S. Fractionated and isolated screening programs are not in accordance with the intrinsic value of youth health care. Therefore an integral approach of the child and its environment demands the maximum incorporation into the PHE of systematic and standardized methods of examination. The concept of the 'group at risk' threatens to supplant the search for the 'child at risk'. Collective health education programs are supplementary to individual counseling and health education, but cannot replace the latter.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4035661 TI - [Screening for congenital hypothyroidism]. AB - In the Netherlands nation-wide screening for CH began in January 1981. The aim of the combined T4-TSH screening method is to detect all forms of CH, primary as well as secondary and tertiary. More than 99% of the newborns are screened. The rate of false-positives in premature infants was reduced in June 1982 by a change of the indications for follow-up. Further study is performed on T4 values of premature infants. The information, given to the parents in case of recall, is not optimal yet. Although there is still delay in screening and follow-up, the initiation of treatment is considerably advanced. The effect of earlier treatment on development will be assessed by Prof. Dr. A. F. Kalverboer. Very likely, the early treatment will lead to a considerable reduction of damage to the central nervous system. PMID- 4035662 TI - [Screening for congenital hip dysplasia in well-child clinics for infants. Current status]. AB - The importance of early detection of congenital dysplasia of the hip (CDH) as well as the examination procedure to be followed is described. In 1984 a retrospective study was carried out among 38 physicians at well-baby clinics in the city and province of Groningen to investigate their method of examination and reasons for referral to the general practitioner for further investigation. CDH was proven in 86 of the 597 referred children (14.4%); this represents 2.7% of the total group of children examined at the clinics. A survey carried out in 1976 showed this number to be 41 of 251 referrals (16.4%) and 3.9% of the total examined group. In 1976 as well as in 1984 proven CDH was most positively correlated with positive signs at physical examination. A positive family history was the most frequent reason for referral, but was poorly correlated with proven CDH. The physicians at the well-baby clinics encountered the following problems: 1. Delay of treatment resulting from referral to a specialist other than the orthopaedic surgeon. 2. Incomplete registration of the total number of infants in care at several well-baby clinics. 3. The decision whether or not to refer a baby in case of minor physical abnormalities and/or a weak positive family history. Finally, recommendations are given for CDH-examinations at well-baby clinics and a suggestion is given for a nation-wide incidence study. PMID- 4035663 TI - Microsomal cytochrome P-450 "handprints": five fractions from anion-exchange high pressure liquid chromatography provide a rapid preliminary screen for selectivity in the induction and destruction of rat hepatic cytochrome P-450 subpopulations. AB - Anion-exchange HPLC was used to monitor changes in rat hepatic cytochrome P-450 fractions resulting from animal exposure to several inducing and hepatotoxic agents. The column eluant was divided into five fractions and the cytochrome P 450 content in each was determined. Induction of hepatic cytochrome P-450 following 2,5-hexanedione and SKF 525-A pretreatment of animals showed an induction pattern in the five-fraction "handprint" similar to that produced by phenobarbital. The patterns of induction following beta-naphthoflavone, clofibrate, and isosafrole pretreatments were unique in comparison to each other and also compared to that of phenobarbital. The pattern of cytochrome P-450 loss after allyl alcohol was similar to that seen after cobalt chloride treatment, but differed from that seen following acetaminophen administration. Five-fraction quantitation of the eluant from anion-exchange HPLC of microsomes appears to be a useful technique to screen for and convey the effects of previously uncharacterized inducers and the effects of hepatotoxic agents or heme synthesis inhibitors on rat hepatic cytochrome P-450 subpopulations. PMID- 4035664 TI - Percutaneous absorption in man: a kinetic approach. AB - A biophysically based kinetic model of chemical absorption via human skin was developed and applied to the penetration kinetics of 12 chemicals: aspirin, benzoic acid, benzyl nicotinate, caffeine, chloramphenicol, colchicine, dinitrochlorobenzene, diethyltoluamide, malathion, methyl nicotinate, nitrobenzene, and salicylic acid. The pharmacokinetic model is linear and includes four first-order rate constants: (1) k1 describes penetrant diffusion through the stratum corneum; (2) k2 relates to further transport across the viable epidermal tissue to the cutaneous blood vessels; (3) k3 is a parameter which delays the partitioning of penetrant at the stratum corneum-viable tissue interface and, in conjunction with k2, reflects the penetrant's relative affinity for the stratum corneum over the viable tissue; and (4) k4 characterizes the elimination rate of chemical from blood to urine. Previously determined diffusion coefficients and molecular weight corrections were used to estimate k1 and k2; k4 values employed were those measured experimentally. Urinary excretion rate data following topical administration were simulated and k3 was estimated for each penetrant by optimizing the fit of the model to the data points. Ratios of k3/k2 should be related to the partition coefficients for the chemicals between stratum corneum and viable tissue and it was shown that these ratios agreed reasonably well with the corresponding octanol-water partition coefficients. This approach may have potential for predicting the general percutaneous absorption kinetics of chemicals based on recognized cutaneous biology and penetrant molecular weight and lipophilicity. PMID- 4035665 TI - Toxicity of carbon disulfide in developing rats: LD50 values and effects on the hepatic mixed-function oxidase enzyme system. AB - The 24-hr LD50 values of carbon disulfide (CS2) were estimated in 1-, 5-, 10-, 20 , 30-, and 40-day-old rats. CS2 was least toxic to 20-day-old rats (LD50 1545 mg/kg, ip) and most toxic to 1-day-old rats (LD50 583 mg/kg, ip). Twenty-four hours after administration of CS2 (375 mg/kg, ip) to 1-, 5-, 10-, 20-, 30-, and 40-day-old rats, significant inhibition of cytochrome P-450 and aniline hydroxylation was observed in rats of all ages studied except the 1-day-old rats. Following incubation of hepatic microsomes isolated from 1-, 5-, 10-, 20-, 30-, and 40-day-old rats with CS2, decreases in activity of the hepatic mixed-function oxidase enzyme system and/or concentration of cytochrome P-450 were observed when an NADPH-generating system was present during incubation. When hepatic microsomes isolated from rats of all ages studied were incubated with C35S2, 35S was covalently bound to microsomal protein in the presence of an NADPH-generating system. Also, more 35S than 14C was covalently bound to microsomal membranes after incubation of microsomes isolated from rats of all ages studied with C35S2 or 14CS2 in the presence of an NADPH-generating system. The results of this research demonstrated the LD50 of CS2, the effects of CS2 on the hepatic mixed function oxidase enzyme system, and that the conversion of CS2 to a covalently binding sulfur-containing biotransformation product varied with age in developing rats. PMID- 4035666 TI - Dose-related effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in C57BL/6J and DBA/2J mice. AB - The dose-related effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) were studied in B6D2F1/J (B6D), C57BL/6J (C57), and DBA/2J (DBA) mice. A 14-fold difference in lethality was observed in C57 and DBA mice, based upon 30-day LD50 values of 182 and 2570 micrograms TCDD/kg body wt, respectively. The 30-day LD50 for B6D mice was 296 micrograms TCDD/kg body wt. A progressive loss of body weight in all strains of mice was observed during the 30-day LD50 studies, with maximal weight losses of 24.7, 34.0, and 33.4% prior to death of C57, B6D, and DBA mice, respectively. In separate experiments, it was found that decreased feed consumption did not contribute to weight loss in C57 mice exposed to lethal or sublethal doses of TCDD until the animals were moribund. Time-course studies in C57 mice treated with 200 micrograms TCDD/kg body wt indicated that decreases in serum glucose and triglyceride concentrations and increases in hepatic triglyceride content occurred within 4 to 8 days of exposure, and were maximally altered within 17 to 21 days postexposure, concomitant with a 25% body weight loss. C57 mice fasted for 24 to 96 hr lost 18% of body weight and also exhibited alterations in glucose and lipid parameters; however, these changes were substantially different than the effects of TCDD exposure. In concert, these observations demonstrate that decreased feed consumption (hypophagia) does not account for weight loss and changes in carbohydrate and lipid metabolism in TCDD treated C57 mice. Dose-response experiments resulted in comparable changes in glucose and lipid parameters when DBA mice were exposed to 10-fold higher doses of TCDD than C57 mice. Parallel LD50 responses and parallel changes in carbohydrate and lipid metabolism, at 10- to 15-fold differences in dose range, are indicative of a common mechanism of toxicity in TCDD-treated C57 and DBA mice. PMID- 4035667 TI - Effects of various trace metals on the binding of cadmium to rat hepatic metallothionein determined by the Cd/hemoglobin affinity assay. AB - The Cd/hemoglobin affinity assay is finding increasing use as an indicator of metallothionein in a variety of biological tissues. Because the assay relies on the ability of heat-stable proteins to bind Cd, it is important to know the relative affinities of different trace metals to bind to such proteins, relative to Cd. This study examines the ability of 15 trace metals to prevent the binding of Cd to metallothionein using the Cd/hemoglobin affinity assay for metallothionein. Cd, Cu, Hg, and Ag were the only metals tested which significantly inhibited the binding of a fixed concentration (2 microM) of 109Cd to a crude preparation of rat hepatic metallothionein. As, Co, Cr, Fe, Mn, Mo, Ni, Pb, Sn, Th, and Zn had no inhibitory effect at the highest concentrations tested. However, As, Sn, Th, and Zn prevented the precipitation of hemoglobin at relatively low concentrations and, thus, could not be fully tested for inhibitory potency. Cu was the most potent inhibitor, producing more than 90% inhibition at 5 microM, followed by Ag, Hg, and Cd, which produced 76, 72, and 65% inhibition of cadmium binding at 5 microM, respectively. These results suggest that caution should be taken in interpreting metallothionein concentrations obtained by the Cd/hemoglobin affinity assay in tissues which contain relatively a high concentration of Cu, Ag, or Hg, relative to that of Cd. PMID- 4035668 TI - Teratological assessment of five oxidative hair dyes in the rat. AB - The oxidative dyes, 4,4'-diaminodiphenylene sulfate, N'-(2-hydroxyethyl)-4-nitro O-phenylenediamine, N,N-dimethyl-p-phenylenediamine, 2,3-dihydroxynaphthalene, and resorcinol, were evaluated for teratogenic potential. Dyes were administered by gavage to pregnant Sprague-Dawley rats on gestation Days 6 through 15 at doses ranging from 12.5 to 500 mg/kg. No overt signs of toxicity were observed during the treatment period. A significant reduction in mean maternal weight gain was noted during the treatment period at the high dose for 4,4'-diaminodiphenylene sulfate, N'-(2-hydroxyethyl)-4-nitro-O-phenylenediamine, and 2,3 dihydroxynaphthalene. The high dose for N,N-dimethyl-p-phenylenediamine and resorcinol, which exceeded a 100-fold exaggeration of human exposure, did not produce a significant reduction in maternal weight gain. An evaluation of fetal external, visceral, and skeletal anomalies revealed no statistically significant differences between dye-treated and vehicle control groups. Administration of 100,000 units of vitamin A, the positive control, on Day 9 of gestation resulted in a significant increase in abnormal fetuses. PMID- 4035669 TI - Effects of feeding stannous chloride on different parts of the gastrointestinal tract of the rat. AB - The effects of feeding inorganic tin on the gastrointestinal tract were examined in rats. Three groups of male weanling Wistar rats were fed a diet to which 0, 250, or 500 ppm Sn2+ had been added as SnCl2. A fourth group was subjected to feed restriction by pair feeding with the 500-ppm group. Comparison of the data from the tin-fed groups with both the control and the reduced diet groups allowed discrimination between effects of reduced feed intake and Sn2+ effects. Independent of the reduced feed intake, Sn2+ affected hemoglobin concentration in the blood and several small intestine parameters. Total length of the small intestine, as well as absolute and relative weights, was increased. An increase was also observed in the migration of epithelial cells along the villus, as revealed by [3H]thymidine incorporation and autoradiography in rats fed 900 ppm Sn2+ for 4 weeks. Stereo-light microscopy and scanning electron microscopy revealed the formation of ridge-like villi due to Sn2+ feeding and a decreased number of villi per unit surface. These data suggest that an increase in cell turnover in the small intestine, due to Sn2+, was responsible for these changes. PMID- 4035670 TI - Functional and morphologic changes in the lungs of guinea pigs exposed to freshly generated ultrafine zinc oxide. AB - Guinea pigs were exposed by nose only for 3 hr/day for 6 days to freshly formed zinc oxide (ZnO) particles (projected area diameter = 0.05 micron, sigma g = 2.0) at 5 mg/m3, the currently recommended threshold limit value (TLV). Ventilation, lung mechanics, lung volumes, and diffusing capacity for carbon monoxide (DLCO) in anesthetized, tracheostomized animals at 1, 24, 48, or 72 hr after the end of the last exposure were evaluated. At the same time intervals lung weight, lung fluid content, respiratory epithelial permeability to horseradish peroxidase, gross and microscopic appearance, and [3H]thymidine labeling of nuclei of bronchial and bronchiolar epithelial cells in other groups of animals were measured. Vital capacity, functional residual capacity, alveolar volume, and DLCO were all decreased following the last exposure and did not return to normal values by 72 hr. Increases in flow resistance and decreases in compliance and total lung capacity returned to normal by 72 hr. Lung weights were elevated due to inflammation involving the proximal portion of the alveolar ducts and adjacent alveoli. These changes were still present at 72 hr. [3H]Thymidine labeling of bronchiolar epithelial cell nuclei was increased for 48 hr. Respiratory epithelial permeability to horseradish peroxidase was not affected by the exposures. These results suggest that the current TLV for ZnO may not be adequate. PMID- 4035671 TI - Acetaminophen nephrotoxicity in the rat: quantitation of renal metabolic activation in vivo. AB - Renal cortical necrosis induced by acetaminophen (APAP) may be related to generation of reactive intermediates by two mechanisms of metabolic activation, direct P-450 dependent metabolic activation (P-450) or metabolic activation subsequent to deacetylation of APAP to p-aminophenol (PAP). Generation of arylating intermediates by both pathways of metabolic activation was quantified in cyclohexamide (HEX)-pretreated or naive rats in vivo with specifically labeled [14C]APAP. The association of each type of metabolic activation with APAP-induced nephrotoxicity was determined in Fischer 344 (F344) and Sprague-Dawley (SD) rats, strains that are susceptible and resistant to APAP-induced nephrotoxicity, respectively. Covalent binding of [ring-14C]APAP to renal cortex was approximately four times greater than [acetyl-14C]APAP in HEX-pretreated F344 rats. In contrast, in SD rats pretreated with HEX covalent binding of [ring 14C]APAP and [acetyl-14C]APAP in the renal cortex was not different. Furthermore, covalent binding of [ring-14C]APAP to renal cortical protein was approximately four times greater in F344 rats than in SD rats. Arylation of hepatic protein by either [ring-14C]APAP or [acetyl-14C]APAP was similar regardless of strain or pretreatment regimen. These studies demonstrated arylation of renal macromolecules in vivo by reactive intermediates resulting from PAP in F344 but not SD rats. Since F344, but not SD, rats are susceptible to APAP-induced nephrotoxicity, it appears the formation of arylating intermediates by PAP is a requisite step in APAP-induced nephrotoxicity. PMID- 4035672 TI - Disposition and metabolism of 2,3-[14C]dichloropropene in rats after inhalation. AB - 2,3-Dichloropropene (2,3-DCP) is a constituent of some commercially available preplant soil fumigants for the control of plant parasitic nematodes. Human exposure potential exists during manufacture of the chemicals or during bulk handling activities. The purpose of this investigation was to determine the disposition and metabolism of 2,3-[14C]DCP in rats after inhalation. Male Fischer 344 rats were exposed nose-only to a vapor concentration of 250 nmol 2,3 [14C]DCP/liter air (7.5 ppm; 25 degrees C, 620 Torr) for 6 hr. Blood samples were taken during exposure, and urine, feces, expired air, and tissues were collected for up to 65 hr after exposure. Urinary excretion was the major route of elimination of 14C (55% of estimated absorbed 2,3-DCP). Half-time for elimination of 14C in urine was 9.8 +/- 0.05 hr (means +/- SE). Half-time for elimination of 14C feces (17% of absorbed 2,3-DCP) was 12.9 +/- 0.14 hr (means +/- SE). Approximately 1 and 3% of the estimated absorbed 2,3-[14C]DCP were exhaled as either 2,3-[14C]DCP or 14CO2, respectively. Concentrations of 14C in blood increased during 240 min of exposure, after which no further increases in blood concentration of 14C were seen. 14C was widely distributed in tissues analyzed after a 6-hr exposure of rats to 2,3-[14C]DCP. Urinary bladder (150 nmol/g), nasal turbinates (125 nmol/g), kidneys (84 nmol/g), small intestine (61 nmol/g), and liver (35 nmol/g) were tissues with the highest concentrations of 14C immediately after exposure. Over 90% of the 14C in tissues analyzed was 2,3-DCP metabolites. Half-times for elimination of 14C from tissues examined ranged from 3 to 11 hr. The data from this study indicate that after inhalation 2,3-DCP is metabolized in tissues and readily excreted. PMID- 4035673 TI - The origin of metallothionein in red blood cells. AB - The origin of metallothionein (MT) in red blood cells (RBCs) from a mouse given cadmium was studied in connection with RBC kinetics. Plasma Cd concentration rapidly decreased 3 hr following 109CdCl2 (2 mg/kg, sc) administration, whereas RBC Cd increased from 2 to 4 days, followed by a gradual decrease. RBC Cd was found to be distributed more in the high-molecular-weight fraction than in the MT fraction 12 hr after administration. But, thereafter, Cd increased rapidly in the MT fraction to show changes with time similar to Cd level in RBCs. Hepatic damage induced in a mouse given 21 injections of Cd, with resultant marked elevation of plasma MT concentrations, did not cause any change in RBC Cd concentration. MT was hardly transferred to RBC when a mouse RBC suspension was incubated with mouse hepatic MT. To examine the relationship of Cd-MT and erythropoietic function, mice in the normal group, the phenylhydrazine-induced anemia group (PH), the transfusion-induced plethora group (TR), and the erythropoietin administered plethora group (TR + EP) were given 109CdCl2. Three days after administration, Cd concentration in its RBCs and its MT fraction remarkably increased in the PH group, and was greatly decreased in the TR group. A significant increase was noted in the TR + EP group as compared with the TR group. These results indicate that MT in the RBCs is formed in erythroblasts. PMID- 4035674 TI - Development of locomotor activity of rat pups exposed to heavy metals. AB - Cadmium (Cd), triethyltin (TET), and trimethyltin (TMT) are heavy metals which are neurotoxic to developing animals. In the present experiment, preweaning assessment of locomotor activity was used to detect and differentiate between the developmental toxicity of these metals. On postnatal day (PND) 5, rat pups received a single injection of either Cd, TET, or TMT. A within-litter design was used for dosing; 1 male and 1 female pup from each litter (N = 10 litters/compound) received either the vehicle, low, medium, or high dosage of the compound. Preweaning motor activity was assessed in 30-min sessions in figure eight mazes from PND 13 to 21. Motor activity of control animals progressively increased in the initial days of testing, and then both within-session and between-session habituation developed. A single exposure to Cd, TET, and TMT produced hyperactivity by the end of the preweaning period but these metals differed in the day of peak activity, the onset of hyperactivity, and the development of habituation. PMID- 4035675 TI - Functional and structural alterations of the rat kidney induced by the naturally occurring organonitrile 2S-1-cyano-2-hydroxy-3,4-epithiobutane. AB - The organonitriles, 2S-1-Cyano-2-hydroxy-3,4-epithiobutane (erythro and threo) (CHEB), isolated from the seed of Crambe abyssinica were administered by gavage to male Fischer-344 rats. Rats given 50 mg/kg/day were killed at 24, 48, and 72 hr. The rats given 100 mg/kg/day were killed at 48 and 72 hr. Serum urea nitrogen and creatinine were increased by 48 hr and further elevated by 72 hr. Glomerular filtration rate (GFR) of the 50 mg/kg CHEB rats was elevated at 24 hr but fell to subnormal values by 72 hr. The GFR of the 100-mg/kg group was decreased at 48 and 72 hr. Urine output of the 50-mg/kg group increased continuously through 72 hr, while urine output of the 100-mg/kg group was increased to a lesser degree. Urinary N-acetyl-beta-D-glucosaminidase (NAG) activity (nmol/hr/mg creatinine) was significantly elevated in both groups by 48 hr, and further increased by 72 hr. Twenty-four hours after administration of 50 mg/kg, renal proximal tubular epithelial cells of some rats had fine cytoplasmic vacuolation. At 48 and 72 hr, necrosis and coarse vacuolation of proximal tubular epithelial cells occurred in both dose groups. The necrosis was most severe at the apexes of the medullary rays and the coarse vacuolation extended deeply toward the outer stripe of the outer zone of the medulla. Higher doses and/or longer times of CHEB administration resulted in a more extensive lesion distribution. It is concluded that CHEB induces nephrotoxicity in rats characterized by nonoliguric, acute renal failure, and morphological lesions preferentially involving the pars recta of the proximal tubules. PMID- 4035676 TI - Comparison of the severity of the chronic cardiotoxicity produced by doxorubicin in normotensive and hypertensive rats. AB - A comparison was made of the severity of chronic doxorubicin cardiotoxicity in adult male spontaneously hypertensive rats (SHR) and in genetically related normotensive Wistar-Kyoto rats (WKY). Groups of SHR and WKY were given 12 weekly iv injections of doxorubicin at 0.25, 0.5, or 1.0 mg/kg. When the study was concluded, mean arterial pressure was 127 to 161 nm Hg in doxorubicin-treated SHR compared with 74 to 87 mm Hg in similarly treated WKY. Lesions, consisting mainly of cytoplasmic vacuolization and myofibrillar loss, were noted in the hearts from both types of rats given the 1.0-mg/kg dose and were considerably more severe in SHR than in WKY (average scores 3.8 and 2.0). Renal lesions (glomerular vacuolization and dilatation of tubules with accumulations of proteinaceous material) were of comparable severity in both types of rats at the 9- and 12 mg/kg cumulative doses; however, they were more severe in SHR at the 6-mg/kg cumulative dose. Moderate cardiac alterations were present in all SHR (average score 1.6) given 0.5 mg doxorubicin/kg; at the same dose, lesions were minimal in two and absent in three WKY. In a second study, groups of rats were killed 1 week after 3,6,9, or 12 weekly iv injections of doxorubicin (1.0 mg/kg). Myocardial lesions were noted initially in SHR after six doses and in WKY after nine doses. Three of five SHR were dead by the 12th dose. These results indicate that spontaneously hypertensive rats are much more sensitive than normotensive rats to the cardiotoxic effects of doxorubicin. PMID- 4035677 TI - Uptake and excretion of [14C]methyl bromide as influenced by exposure concentration. AB - Methyl bromide is a widely used soil fumigant and poses potential inhalation hazard to workers. Uptake of methyl bromide and pathways for excretion of 14C were investigated in male Fischer-344 rats after nose-only inhalation of 50, 300, 5700, or 10,400 nmol (1.6 to 310 ppm) of [14C]methyl bromide/liter of air for 6 hr. Fractional uptake of methyl bromide decreased at the highest concentrations, 5700 and 10400 nmol/liter, with 37 and 27% of the inhaled methyl bromide absorbed, respectively, compared to 48% at the lower levels. This resulted in the same total amount of methyl bromide being absorbed at the two higher exposure concentrations (650 mumol/kg body wt). Total methyl bromide adsorbed was 9 or 40 mumol/kg body wt after exposure to 50 or 300 nmol/liter, respectively. Elimination of 14C was linearly related to the amount of methyl bromide absorbed as determined from urine, feces, expired CO2, and parent compound collected for 66 hr after the end of exposure. Exhaled 14CO2 was the dominant route of excretion, with from 1.2 to 110 mumol (50% of amount absorbed) exhaled, and was described by a two-component negative exponential function; 85% was exhaled with a t 1/2 of 4 hr, and the remaining 15% was exhaled with a t 1/2 of 17 hr. The rate of exhalation of 14CO2 was not affected by the amount of [14C]methyl bromide absorbed. From 0.4 to 54 mumol was excreted in urine (20% of amount absorbed). The half-time for excretion of 14C in urine was approximately 10 hr, and the rate of excretion was not dependent on the amount of [14C]methyl bromide absorbed. Little 14C was exhaled as methyl bromide (less than 4% of the dose) or excreted in feces (less than 2%). At the end of 66 hr, 25% of the 14C absorbed remained in the rats. Liver, kidneys, adrenals, lungs, thymus, and turbinates (maxilloturbinates, ethmoturbinates, and nasal epithelial membrane) contained the highest concentrations of 14C. Results indicated that uptake of inhaled methyl bromide could be saturated. Any [14C]methyl bromide equivalents absorbed, however, would be excreted by concentration-independent mechanisms. PMID- 4035678 TI - In vitro modulation of bovine caudate muscarinic receptor number by organophosphates and carbamates. AB - In vitro binding assays to measure muscarinic receptor number and affinity were carried out with isolated synaptic plasma membranes from bovine caudate nuclei. Diethyl-p-nitrophenyl phosphate (paraoxon; PX), dichlorvos (DDVP), and tetraethyl pyrophosphate (TEPP) were demonstrated to be weak noncompetitive receptor inactivators. PX, DDVP, and TEPP decreased the number of [3H]quinuclidinyl benzilate (QNB) binding sites by 16 to 31% and exhibited no significant effect on the affinity of central muscarinic receptors for QNB (KD congruent to 0.3 nM). QNB binding was inhibited by PX at 5 nM, DDVP at 50 nM, and TEPP at 50 nM, concentrations with no effect on acetylcholinesterase activity. Similar measurements with two carbamates, physostigmine and neostigmine (1 nM), showed no effect of neostigmine on QNB binding, while physostigmine both decreased the number of receptors and enhanced their affinity for QNB. The modulation of muscarinic receptors by 5 nM PX was abolished by carbodiimide modification of the membrane preparation. It is suggested that a decrease in the number of muscarinic cholinergic receptors in the brain may underlie some of the neurological and affective disorders observed after chronic exposure of humans to organophosphate insecticides. PMID- 4035679 TI - The effects of triethyltin and trimethyltin in rats responding under a DRL schedule of reinforcement. AB - Rats were trained to respond under a schedule of reinforcement in which only those responses separated by a 10-to 14-sec period of no responding produced a feed pellet (DRL 10 to 14 sec). Each rat received a single dose of trimethyltin (TMT) (5.6, 7.5, or 10 mg/kg) or triethyltin (TET) 1, 3, 4.25, or 5.6 mg/kg). The lowest dose of TMT (5.6 mg/kg) and the lowest dose of TET (1 mg/kg) were without significant effect. At 7.5 mg/kg and 10 mg/kg TMT, the percentage of the total responses spaced 10 to 14 sec apart decreased over the first 8 to 12 days after TMT. Those rats receiving 7.5 mg/kg TMT gradually returned to control values over the next 2 to 3 weeks while those rats receiving 10 mg/kg never recovered. Rats receiving 3, 4.25, and 5.6 mg/kg TET showed a decrease in the percentage of reinforced responses immediately after receiving TET. The behavior of those rats receiving 3 mg/kg returned to control values in 24 hr. Following 4.25 mg/kg TET, the health of the rats deteriorated rapidly. They were kept alive through heroic measures, but then were killed after testing on the 12th day following TET due to their failing health. At 5.6 mg/kg, the rats were killed on the 4th day due to failing health. These results indicate that TMT and TET differ with respect to potency and time course. The behavioral deficits produced by TET parallel the time course of general toxicity while the behavioral effects of acute TMT administration can persist in time long after the general appearance of the rats has returned to normal. PMID- 4035680 TI - Disposition of [14C]methyl bromide in rats after inhalation. AB - Methyl bromide is used as a disinfectant to fumigate soil and a wide range of stored food commodities in warehouses and mills. Human exposure occurs during the manufacture and use of the chemical. The purpose of this investigation was to determine the disposition and metabolism of [14C]methyl bromide in rats after inhalation. Male Fischer-344 rats were exposed nose only to a vapor concentration of 337 nmol [14C]methyl bromide/liter air (9.0 ppm, 25 degrees C, 620 torr) for 6 hr. Urine, feces, expired air, and tissues were collected for up to 65 hr after exposure. Elimination of 14C as 14CO2 was the major route of excretion with about 47% (3900 nmol/rat) of the total [14C]methyl bromide absorbed excreted by this route. CO2 excretion exhibited a biphasic elimination pattern with 85% of the 14CO2 being excreted with a half-time of 3.9 +/- 0.1 hr (means +/- SE) and 15% excreted with a half-time of 11.4 +/- 0.2 hr. Half-times for elimination of 14C in urine and feces were 9.6 +/- 0.1 and 16.1 +/- 0.1 hr, respectively. By 65 hr after exposure, about 75% of the initial radioactivity had been excreted with 25% remaining in the body. Radioactivity was widely distributed in tissues immediately following exposure with lung (250 nmol equivalents/g), adrenal (240 nmol equivalents/g), kidney (180 nmol equivalents/g), liver (130 nmol equivalents/g), and nasal turbinates (110 nmol equivalents/g) containing the highest concentrations of 14C. Radioactivity in livers immediately after exposure accounted for about 17% of the absorbed methyl bromide. Radioactivity in all other tissues examined accounted for about 10% of the absorbed methyl bromide. Elimination half-times of 14C from tissues were on the order of 1.5 to 8 hr. In all tissues examined, over 90% of the 14C in the tissues was methyl bromide metabolites. The data from this study indicate that after inhalation methyl bromide is rapidly metabolized in tissues and readily excreted. PMID- 4035681 TI - Performance and exposure indices of rats exposed to low concentrations of lead. AB - To further characterize the lower end of the function relating lead exposure and biological exposure indices to behavior, male weanling rats were exposed chronically to drinking solutions containing 25 ppm sodium acetate (controls) or 25 ppm lead acetate. Behavioral training began when the animals reached 50 days of age, and performance on a fixed-interval 1-min schedule of food reinforcement was then assessed over 90 experimental sessions (136 days). This exposure produced overall response rate increases over the first 40 sessions that were similar to those observed previously with higher concentrations of lead. Response rates of the two groups tended to merge subsequently. The increased overall response rates in the treated group derived primarily from an increased frequency of shorter interresponse times (IRTs) and increased running rates (calculated without the postreinforcement interval). Blood lead (PbB) and zinc protoporphyrin (ZPP) values were determined following sessions 30, 60, and 90. PbB values of the lead-exposed group averaged 15 to 20 micrograms/dl throughout the study; ZPP did not differ. The mean brain lead value of the treated group was 0.07 micrograms Pb/g. Blood-brain ratios (1.38 to 4.06) were substantially greater than those previously observed at higher exposures. These data extend to even lower exposures, and lower blood lead concentrations, the effective concentration for behavioral effects, and further emphasize the importance of the sensitivity of the endpoint in assessing behavioral toxicity. PMID- 4035682 TI - Role of 3,5-dichlorophenyl methyl sulfone, a metabolite of m-dichlorobenzene, in the induction of hepatic microsomal drug-metabolizing enzymes by m dichlorobenzene in rats. AB - The increases in the hepatic microsomal aminopyrine N-demethylase activity and in the content of cytochrome P-450 produced by m-dichlorobenzene (m-DCB) occurred after increases in the hepatic concentration of 3,5-dichlorophenyl methyl sulfone, a minor metabolite. The extent of increases in aminopyrine N-demethylase activity and in the content of cytochrome P-450 at 48 hr after po administration of 200 mg/kg (1.36 mmol/kg) of m-DCB was almost equal to that 72 hr after the ip administration of 25 mumol/kg of the sulfone (Kimura et al., 1983). m-DCB in liver was not detectable at that time, and the concentration of sulfone was 63 to 70% of that 48 to 72 hr after the ip administration of 50 mumol/kg of sulfone. Administration of m-DCB (200 mg/kg) produced a significant reduction in hexobarbital sleeping time, but this reduction was less than that produced by administration of the sulfone (50 mumol/kg). The protein band patterns by sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the microsomes from rats treated with the sulfone and m-DCB were similar to those of phenobarbital-treated rats but were different from those of 3-methylcholanthrene-treated rats. The sulfone showed type I interaction with the cytochrome P-450 (Ks, 0.17 mM). The sulfone was formed from the sulfide but reduction of the sulfone was not observed when it was incubated in a hepatic microsomal preparation. The pattern of induction by the sulfone and m-DCB was similar to that by phenobarbital and differed from that by 3-methylcholanthrene. From these results, 3,5 dichlorophenyl methyl sulfone is considered to be a major contributing factor of the inducing activity of m-DCB and to be a potent phenobarbital-like inducer. PMID- 4035683 TI - The half-lives of alkylating intermediates from diethylnitrosamine and N nitrosopyrrolidine: a method for the measurement of metabolically generated reactive species. AB - The half-times of the alpha-hydroxylated intermediates formed during metabolism of diethylnitrosamine and N-nitrosopyrrolidine have been determined. The method for determining half-times involved in vitro enzymatic conversion of the nitrosamine to a hydroxylated intermediate followed by trapping of the alkylating species generated from the chemical decomposition of the intermediate as it flowed through a column containing bound nucleophile. Half-times of less than 1 min at pH 7.4, 37 degrees C, were calculated from the distribution of alkylation on the column and the known flow rate of metabolic intermediates through the column. The half-times may be short enough to significantly limit organ distribution. PMID- 4035684 TI - Biochemical, histological, and ultrastructural changes in rat and mouse liver following the administration of trichloroethylene: possible relevance to species differences in hepatocarcinogenicity. AB - Trichloroethylene (TRI), administered by gavage for 10 consecutive days, at doses of 500 to 1500 mg/kg body wt increased liver weight (175% of control), decreased hepatic DNA concentration (66% of control), and increased the synthesis of DNA (500% of control; as measured by [3H]dT incorporation) in B6C3F1 mice and Alderley Park mice. Similar treatment of Osborne-Mendel rats or Alderley Park rats resulted in smaller increases in liver weight (130% of control) and decreases in DNA concentration (83% of control). No effect of TRI on DNA synthesis was seen in rats. The increased DNA synthesis in the mouse was not apparently due to regenerative hyperplasia since no signs of necrosis were seen. Furthermore the increased [3H]dT incorporation probably represented semiconservative replication of DNA and not repair, since a parallel increase of mitotic figures was observed. Hence, the liver growth noted after TRI administration appears to be due to liver cell enlargement (hypertrophy) in the rat, but both hypertrophy and hyperplasia (cell proliferation) in the mouse. An important observation has been that TRI induced the peroxisomal enzyme activities, catalase, and cyanide-insensitive palmitoyl-CoA oxidation (147 and 786% of control, respectively), in mice but not in rats. Furthermore, increases in peroxisome volume density (up to 1110% of control) were observed in mice receiving TRI. These observations lead us to suggest that the species difference in hepatocarcinogenicity of TRI, seen between the rat and mouse, is possibly due to a species difference in peroxisome proliferation and cell proliferation, the peroxisome proliferation leading to increased reactive oxygen species and DNA damage, and the cell proliferation then acting to promote this lesion. PMID- 4035686 TI - Species differences in response to trichloroethylene. I. Pharmacokinetics in rats and mice. AB - The elimination of radioactivity in two strains of rats and mice following a single po dose of trichloro[14C]ethylene at dose levels from 10 to 2000 mg/kg has shown a marked dose dependence in rats but not in mice. The metabolism of trichloroethylene in the mouse was linear over the range of doses used, whereas in the rat it became constant and independent of dose at 1000 mg/kg and above. At the 10-mg/kg dosage, both species metabolized trichloroethylene almost completely, 60% of the dose being excreted in urine with only 1 to 4% being eliminated unchanged in expired air in the first 24 hr. At 2000 mg/kg, 78% of the dose was eliminated unchanged in the rat, but only 14% in the mouse. Consequently at high dosages, the mouse was exposed to significantly higher concentrations of trichloroethylene metabolites than the rat. Blood level kinetics of trichloroethylene and its metabolites confirmed a faster rate of metabolism in the mouse than in the rat. Peak concentrations of the metabolites were reached within 2 hr of dosing in the mouse compared to 10 to 12 hr in the rat. The concentrations of both trichloroethanol (4X) and trichloroacetic acid (7X) were significantly higher in the mouse than in the rat. Whereas trichloroethanol was rapidly eliminated from blood, the higher concentrations of trichloroacetic acid were maintained for over 30 hr. The high blood quantities of trichloroethylene derived trichloroacetic acid are known to induce hepatic peroxisome proliferation in mice but are insufficient to induce this response in rats. These data suggest that trichloroacetic acid blood amounts, peroxisome proliferation, and the link between peroxisomes and liver cancer are the basis of species difference in response to trichloroethylene. PMID- 4035685 TI - Cutaneous and auditory function in rats following methyl mercury poisoning. AB - Rats were given a total dose of 50 mg/kg (Exp. 1), 13.3 or 40 mg/kg (Exp. 2), or 40 mg/kg (Exp. 3) of methyl mercury chloride subcutaneously over a course of 5 days. At varying times after the toxic exposure, up to 1 year, their sensory functioning was assessed by reflex modulation methods: stimuli of interest were presented just before an intense tone which elicited the startle reflex, and stimulus reception was measured by the inhibitory control of the stimuli over the amplitude of the reflex. In Experiment 1 cutaneous prestimuli (electric shock to the tail) and brief acoustic transients (silent periods in noise) were less effective inhibitors of reflex activity in poisoned animals, compared to controls, indicating that the poisoned animals had impairments in cutaneous sensitivity and audition. In Experiment 2 the time course of sensory loss and subsequent recovery was studied. Impaired auditory function was shown further by a deficit in the effectiveness of weak noise pulses, and, in addition, the cutaneous deficit for weak tail shocks was accompanied by an exaggerated or hyperpathic response to more intense tail shocks. Experiment 3 confirmed the finding that the loss of sensitivity to weak shock was accompanied by an enhancement of the response to more intense shock. These data were related to peripheral neuropathy and shown to be analogous to certain clinical symptoms of Minamata disease reported in humans. PMID- 4035687 TI - Toxicologic and antitumor studies on 5-hydroxymethyldeoxyuridine. AB - Toxic effects of 5-hydroxymethyldeoxyuridine (HMUdR) were studied in white Swiss mice. Pathological, hematological, and clinical chemistry parameters were examined. Systemic toxicity was not observed in mice after ip administration of HMUdR in single doses up to 2000 mg/kg. Mice administered HMUdR daily for 15 days at 200 mg/kg, ip, manifested loss of weight, rough hair coat, diarrhea, swollen abdomens, weakness, lethargy, and a 20% mortality rate. Hematological and clinical chemistry parameters of all mice receiving HMUdR were within normal limits. At necropsy, all organs were grossly normal but microscopic examination of tissues of treated mice revealed the presence of shortened, thickened villi in the small intestine, nuclear vacuolation and necrosis of intestinal crypt epithelial cells, and some cytoplasmic vacuolation causing nuclear margination in hepatocytes. All histological lesions were reversible with cessation of treatment. HMUdR was active against murine L1210 and L5178Y leukemias in cell culture. The concentrations required to inhibit cell growth 50% compared to untreated cells was 2 and 4 microM, respectively. When HMUdR was administered ip at 50, 100, or 200 mg/kg in five daily doses to mice implanted with L1210 cells, life spans increased 20, 30, or 33% over placebo-treated controls. PMID- 4035688 TI - Membrane effects of various drugs on isolated rat hepatocytes and erythrocytes. AB - The relationship between hepatotoxicity and membrane effects of clinically used drugs on erythrocytes was investigated. The cytotoxicity of various drugs to isolated rat hepatocytes was determined by the leakage of glutamic oxalacetic transaminase (GOT) and ornithine carbamyl transferase (OCT) into the surrounding medium. Inhibition of hypotonic hemolysis of rat erythrocytes was measured as the hemoglobin concentration in the supernatant solution. Drugs such as tricyclic antidepressants, local anesthetics (dibucaine), and bile acids (chenodeoxycholic acid), which have both a membrane stabilizing effect on erythrocytes at low concentrations and a hemolytic effect at higher concentrations, induced enzyme leakage from hepatocytes. The concentration at which hemolysis occurred corresponded to the concentration which caused a marked enzyme leakage from hepatocytes. These phenomena were observed for alkyltrimethylammonium salts (C10 to C16), the order of cytotoxicity to hepatocytes and erythrocytes was C16 greater than C14 greater than C12 greater than C10. Marked enzyme leakage was observed for chenodeoxycholic acid at 1 X 10(-3) M but not for ursodeoxycholic acid. The order of membrane stabilizing and lytic potency of tricyclic antidepressants was chlorimipramine greater than amitriptyline greater than desipramine greater than imipramine. These results suggest that these membrane effects of various drugs on erythrocytes may be useful for screening for hepatocytotoxicity in vitro. PMID- 4035689 TI - The role of metabolism in 2-methoxyethanol-induced testicular toxicity. AB - The role of metabolism in 2-methoxyethanol (ME)-induced testicular toxicity has been investigated with Sprague-Dawley rats. Following administration of [14C]ME (250 mg/kg, ip) to a group of animals, there was evidence of testicular damage, identified as depletion of the spermatocyte population. Radioactivity detected in urine over 48 hr after treatment accounted for 55% of the dose. The major urinary metabolites were identified by HPLC and isotope dilution analysis, as methoxyacetic acid (MAA) and methoxyacetylglycine (accounting for 50 to 60% and 18 to 25%, respectively, of urinary radioactivity). Analysis of plasma revealed a rapid conversion of ME to MAA (t1/2 for disappearance of ME = 0.6 +/- 0.03 hr) and gradual clearance of radioactivity (t1/2 = 19.7 +/- 2.3 hr). Pretreatment of animals with pyrazole (400 mg/kg, ip) 1 hr prior to [14C]ME dosing gave complete protection against the testicular toxicity of ME. Radioactivity detected in the urine from the pyrazole-pretreated groups over 48 hr (18%) was significantly lower than in the ME-only group. The major radioactive peak co-chromatographed with ME (30 to 36% of the total urinary radioactivity). MAA and methoxyacetylglycine were not major metabolites. Analysis of plasma revealed almost complete inhibition of the conversion of ME to MAA (t1/2 for disappearance of ME = 42.6 +/- 5.6 hr, clearance of radioactivity t1/2 = 51.0 +/- 7.8 hr). The results demonstrate that metabolic activation is required for 2-methoxyethanol to exert toxicity to the male reproductive system. PMID- 4035690 TI - Studies on the toxicity of some glycol ethers and alkoxyacetic acids in primary testicular cell cultures. AB - Primary mixed cultures of Sertoli and germ cells were prepared from testes of immature rats and their response to the known testicular toxicants ethylene glycol monomethyl ether (EGM) and ethylene glycol monoethyl ether (EGE) was studied. Neither EGM nor EGE produced any morphological evidence of toxicity when added to the culture medium at up to 50 mM for 72 hr. In contrast, their metabolites methoxyacetic acid (MAA) and ethoxyacetic acid (EAA) at 2 to 10 mM for 24 to 72 hr caused degeneration of the pachytene and dividing spermatocytes, the target cells of the parent ethers in vivo. As in vivo, earlier spermatocytes, spermatogonia, and Sertoli cells appeared unaffected. EAA was less potent than MAA whereas n-propoxy- and n-butoxyacetic acid, and methoxyacetylglycine, a further metabolite of MAA, produced no morphological changes under these conditions. The same order of toxicity was observed in concurrent studies with the four acids in rats. In culture, the severity of the morphological changes was paralleled by decreases in the activity of carnitine acetyltransferase and lactate dehydrogenase-X in the attached germ cell fraction. Analysis of culture medium provided no evidence for the conversion of EGM to MAA or other metabolites or for the further metabolism of MAA. The close correspondence between the testicular toxicity of alkoxyacetic acids in culture and in vivo suggests a similar mode of action in both cases and points to the potential value of these cultures for mechanistic studies and for screening purposes. The results also emphasize the role of metabolism in the testicular toxicity of glycol ethers and indicate that MAA is an active metabolite of EGM. PMID- 4035691 TI - Relationship between the pharmacological effects and the biodisposition of [3H]diisopropylfluorophosphate in mice after inhalation. AB - The biodisposition of [3H]diisopropylfluorophosphate (DFP) and its metabolites was studied in mice after inhalation administration. In addition, the time course of DFP-induced cholinesterase inhibition in selected tissues, hypothermia, and motor coordination were studied to determine a possible correlation with [3H]DFP, or its metabolites. The time course of tissue concentrations of [3H]DFP showed that [3H]DFP rapidly penetrated all tissues and was quickly hydrolyzed to [3H]diisopropylphosphoric acid (free [3H]DIP) or was covalently bound to tissue (bound [3H]DIP). By 1 hr, the greater portion of the radioactivity was in the form of bound [3H]DIP. Cholinesterase inhibition in brain, lung, diaphragm, and plasma was temporally related to concentrations of bound [3H]DIP between 5 min and 1 day, except at early time points for the lung. Motor incoordination (rotarod test) produced by DFP exposure had a rapid onset, with complete recovery by 10 hr. DFP-induced hypothermia (rectal temperature) had a very similar time course profile to that of motor incoordination. The time course of hypothermia and motor incoordination was correlated with neither free [3H]DFP nor bound [3H]DIP concentrations in the brain, nor with cholinesterase inhibition in brain. These findings suggest that non-cholinesterase bound [3H]DIP may contribute to the depression of these centrally mediated effects. PMID- 4035692 TI - Resistance to cadmium-induced necrosis in testes of inbred mice: possible role of a metallothionein-like cadmium-binding protein. AB - Altered accumulation and subcellular disposition of testicular Cd were examined as possible explanations for the resistance to Cd-induced testicular damage observed in certain inbred strains of mice. Mouse strains susceptible (129/J) or resistant (A/J) to Cd-induced testicular necrosis were injected iv with 10 or 45 mumol CdCl2/kg, respectively. This dosing regimen compensated for decreased Cd accumulation by A/J testes and established similar concentrations of Cd in testes of both strains (approximately 4 nmol Cd/g tissue). Twenty-four hours later, 129/J testes showed marked interstitial hemorrhage and seminiferous tubule necrosis, while A/J testes showed no microscopic evidence of damage. Two hours postinjection, no histopathologic changes were detected in testes of either strain; however, A/J testes had 15% more Cd associated with the cystosol than 129/J testes, and three times more Cd bound to a 14,500 MW cytosolic protein which had gel filtration and ion-exchange chromatography properties in common with metallothionein (MT). Therefore, resistance of A/J testes to Cd does not appear to be determined solely by decreased Cd accumulation, but is associated with increased binding of testicular Cd to a MT-like protein. However, this increase is not accompanied by a proportional increase in the total Cd-binding capacity of the MT-like protein in A/J testes compared to 129/J testes. PMID- 4035693 TI - Comparison of methods of metallothionein quantification: cadmium radioassay, mercury radioassay, and radioimmunoassay. AB - A comparison of the Hg radioassay (i.e. "Piotrowski" assay), the Cd radioassay (i.e. "cadmium-hemolysate" assay), and the radioimmunoassay (RIA) for metallothionein (MT) was performed for livers from control, Cd-, and Zn pretreated rats. Results indicate that the Cd and Hg radioassays gave similar results in all cases. The RIA values compared very favorably to those obtained by the metal saturation assays for livers from control rats. The values obtained for livers from Cd- or Zn-treated animals were generally lower in the RIA than in the Hg or Cd radioassay, ranging from 36 to 75% of the metal saturation assays. The source of this discrepancy cannot be discerned from the present data. However, the various assay systems employed did yield MT concentrations that followed similar intraassay patterns, being lowest in control, elevated to an intermediate level with Cd treatment, and highest following Zn treatment. PMID- 4035694 TI - Effect of ozone on serum lipids and lipoproteins in the rat. AB - Exposure of male rats to 0 (air), 1, 1.75, and 3 ppm ozone (O3) 5 hr/day for a total of 10 days resulted in a positive linear relationship between ozone concentration and the concentrations of serum total lipoprotein free cholesterol (FCh) and high-density lipoprotein total cholesterol (HDL-Ch). The latter response was reflected in both its free (HDL-FCh) and esterified (HDL-ChE) components. On the other hand, serum triglycerides (TG) showed a marked decreasing linear trend with increasing ozone concentration. As judged by decreased body weights with no accompanying differences in feed consumption, apparent metabolic rate increased as ozone concentration increased. In another experiment, male rats were exposed 5 hr/day to either air or 1 ppm O3 for a total of 15 days. Groups of animals from each exposure were sampled at times ranging from immediately after to 44 hr postexposure. In agreement with the concentration response study, effects of O3 included increases in serum total cholesterol (Ch), HDL-Ch and HDL-FCh, and a decrease in TG. In addition, the degree of effects appeared to be maintained over the 44-hr period and to be greater than that observed at 1 ppm O3 in the concentration-response study. PMID- 4035695 TI - Fate and distribution of 3H-labeled T-2 mycotoxin in guinea pigs. AB - T-2 toxin is a potent cytotoxic metabolite produced by the Fusarium species. The fate and distribution of 3H-labeled T-2 toxin were examined in male guinea pigs. Radioactivity was detected in all body tissues within 30 min after an im injection of an LD50 dose (1.04 mg/kg) of T-2 toxin. The plasma concentration of trichothecene molar equivalents versus time was multiphasic, with an initial absorption half-life equal to or less than 30 min. Bile contained a large amount of radioactivity which was identified as HT-2, 4-deacetylneosolaniol, 3'-hydroxy HT-2, 3'-hydroxy T-2 triol, and several more-polar unknowns. These T-2 metabolites are excreted from liver via bile into the intestine. Within 5 days, 75% of the total radioactivity was excreted in urine and feces at a ratio of 4 to 1. The appearance of radioactivity in the excreta was biphasic. Metabolic derivatives of T-2 excreted in urine were T-2 tetraol, 4-deacetylneosolaniol, 3' hydroxy HT-2, and several unknowns. These studies showed a rapid appearance in and subsequent loss of radioactivity from tissues and body fluids. Only 0.01% of the total administered radioactivity was still detectable in tissues at 28 days. The distribution patterns and excretion rates suggest that liver and kidney are the principal organs of detoxication and excretion of T-2 toxin and its metabolites. PMID- 4035696 TI - Relationship between the biodisposition of [3H]soman and its pharmacological effects in mice. AB - The iv administration of soman (25 micrograms/kg) resulted in inhibition of cholinesterase activity in plasma, brain, and diaphragm, as well as depression of spontaneous activity and rectal temperature in mice. The motor activity and rectal temperature of these animals had returned to control levels within 24 hr, but cholinesterase activity was not fully recovered after 3 days. Following iv administration of [3H]soman (25 micrograms/kg), only trace quantities of [3H]soman were found in all tissues as early as 1 min after injection. Almost half of the injected material was present in the form of free [3H]pinacolylmethylphosphoric acid (PMPA) within 1 min of injection of [3H]soman. The concentrations of [3H]PMPA fell by more than 50% by 1 hr. High concentrations of covalently bound [3H]PMPA were present in all tissues immediately after [3H]soman treatment, particularly in lungs, heart, and kidneys. These concentrations declined slowly and after 8 hr, the quantities of bound [3H]PMPA in most tissues had fallen by less than 50%. The radioactivity in brain was identified as bound and free [3H]PMPA, nonextractable radioactivity (presumably [3H]methylphosphonic acid), and only traces of [3H]soman. It appears that phosphorylation of cholinesterase in the central nervous system is not solely responsible for depression of motor activity and rectal temperature. PMID- 4035697 TI - A method for generating toxic vapors of soman: toxicity of soman by inhalation in rats. AB - A method for administration of highly toxic chemicals by inhalation was developed. The model has three features of special interest: (1) a diffusion cell for producing a constant gas concentration, if necessary for several hours and days, (2) a small rapidly equilibrated inhalation chamber (1100 ml), and (3) complete isolation of the toxic chemicals from the atmosphere. The LCt50 of the anticholinesterase soman [o-(1,2,2 trimethylpropyl)-methyl-phosphonofluoridate] was 400 mg min/m3, registered 24 hr after the end of exposure. The lethal concentration X time of soman was 520 +/- 60 mg min/m3 when exposing the animals until death in the inhalation chamber. The exposure was less than 30 min and the concentration of soman was 21 mg/m3. The inhibition of acetylcholinesterase, cholinesterase, and carboxylesterase activities in different tissues was analyzed to study the possible barrier mechanisms that might exist in the body to soman. There was a large inhibition of the carboxylesterase and cholinesterase activities in bronchi and lungs as well as in blood. Carboxylesterases were important as detoxifying enzymes, as shown by 70% enhancement in toxicity of soman following sc pretreatment with TOCP (tri-ortho-cresyl-phosphate), a carboxylesterase inhibitor. PMID- 4035698 TI - Evaluation of host resistance and immune function in cadmium-exposed mice. AB - Adult female B6C3F1 mice received distilled water only or water containing 10, 50, or 250 ppm of cadmium chloride (CdCl2) for 90 days. Body weights were measured weekly. On selected days during exposure and on Day 91, Cd tissue concentrations were measured along with changes in primary antibody responses. On Day 91 mice also received a primary challenge with various infectious agents. T- and B-cell mitogenesis, natural killer (NK) cell function, delayed type hypersensitivity (DTH) as well as macrophage bactericidal activity, and phagocytosis were measured. There was no change in body weight gain, organ weights, or in humoral immunity during treatment even though cadmium had accumulated in significant quantities in the tissues. Compared with controls, exposure to cadmium had no statistically significant effect on mortality and mean survival time following primary or secondary challenge with any of the infectious agents. However, there was a dose-related, increased susceptibility to Herpes simplex type 2 virus. T- and B-lymphocyte proliferation was significantly reduced, and macrophage phagocytosis was significantly increased following cadmium exposure. NK cell activity was augmented, but not significantly. Macrophage bactericidal activity and DTH were not significantly altered. PMID- 4035699 TI - The effects of methyl mercury binding to microtubules. AB - The effects of methyl mercury hydroxide (MeHg) on the in vitro polymerization and depolymerization of microtubules were studied. Polymerization was totally inhibited at 3.0 X 10(-5) M MeHg and depolymerization occurred at concentrations above 1.0 X 10(-5) M MeHg, reaching a maximal rate of -0.33%/min at 5.0 X 10(-5) M MeHg. At or above 1.0 X 10(-4) M MeHg, a mercury-protein aggregate formed in both the polymerization and depolymerization systems. Fifteen free sulfhydryl groups per tubulin dimer were determined, and MeHg bound to all 15. When MeHg bound to only 2 free sulfhydryl groups per dimer, it inhibited polymerization. MeHg bound to free sulfhydryl groups exposed uniquely on the surface of microtubules, as well as those free sulfhydryl groups exposed on the ends. These results show MeHg in vitro to be a potent microtubule assembly inhibitor at ratios stoichiometric with the tubulin dimer. The effects of MeHg on microtubules are presumably mediated through MeHg binding to free sulfhydryl groups both on the ends and on the surface of microtubules. The presence of binding sites (free sulfhydryl groups) on the microtubule surface suggests multiple classes of binding sites for MeHg. PMID- 4035701 TI - Acrylamide preferentially affects slowly adapting cutaneous mechanoreceptors. AB - Acrylamide (ACR) is a vinyl monomer which produces a distal axonopathy. Several investigators have shown that ACR produces deficits in proprioception. This deficit appears to result in part from altered muscle spindle function. ACR also produces deficits in cutaneous sensory perception. The purpose of these experiments was to determine whether ACR alters cutaneous sensory receptors. Cats were administered ACR (30 mg/kg) for either 3, 5, or 10 days. Following the last injection, the tibial nerve was isolated and four different mechanoreceptor types were isolated. These were field, rapid adapting (RA), and slowly adapting type 1 and type 2. The frequency response of the slowly adapting receptors was normal. However, the number of slowly adapting receptors identified was significantly reduced in all three ACR-treated groups. There was also a decrease in the number of field receptors after 10 day ACR administration. The total number of receptors per tibial nerve was unchanged in the ACR 3- and ACR 5-day groups but was significantly reduced in the ACR 10-day group. These data show a preferential effect of ACR on slowly adapting receptors early in the neuropathy. However, the reduction in field receptors and the total number of receptors at 10 days suggests that ACR eventually affects all mechanoreceptors in the tibial nerve. PMID- 4035700 TI - Short-term toxicity of trans,trans-muconaldehyde. AB - Toxicological and biochemical effects of muconaldehyde, a six-carbon diene dialdehyde, were evaluated in 6- to 9-week-old CD-1 male mice. The LD50 of trans,trans-muconaldehyde was 6.7 and 7.1 mg/kg body wt when calculated by two different methods. Administration of trans,trans-muconaldehyde (2 mg/kg, ip) daily for 10 and 16 days resulted in a statistically significant decrease in red blood cell count, hematocrit, hemoglobin, bone marrow cellularity, and hepatic total and free sulfhydryl content. There was an increase in white blood cell count and spleen weight at 16 days. Similar effects, but of much lesser magnitude, were observed when the mice were given the same total dose of 2 mg/kg divided into three daily ip injections of 0.67 mg/kg trans,trans-muconaldehyde for 10 and 16 days. This alpha,beta-unsaturated aldehyde is a potent bone marrow toxin in mice. PMID- 4035702 TI - Alterations in alveolar clearance after 4-ipomeanol-induced necrosis of Clara and ciliated cells in the terminal bronchiole of the rat. AB - The administration of 4-ipomeanol, [0, 10 (LD), and 25 (HD) mg/kg, ip], to rats resulted in dose-dependent degeneration and necrosis of the nonciliated (Clara) and ciliated epithelial cells of the terminal bronchioles. More extensive necrosis of the terminal bronchiolar epithelium, with exposure of the basement membrane, was produced in the HD group. Repair of the terminal bronchiolar epithelium was complete within 10 days. Alveolar clearance of 51Cr labeled polystyrene latex microspheres was analyzed through 40 days postinstillation by nonlinear regression for a double exponential model. Alveolar clearance during phase 1 (Days 2 to 6) was delayed and significantly decreased in both the LD and HD groups. Alveolar clearance during phase 2 (Days 10 to 40) was significantly decreased only in the HD group. The decreased alveolar clearance in HD subjects was long term and did not correlate with the return of morphologically normal appearing Clara and ciliated cell structure. PMID- 4035703 TI - Methodologies for estimating LD50: the moving average method. PMID- 4035704 TI - Toxicology of indecainide hydrochloride after intravenous administration to rats and dogs. AB - Subchronic 1-month intravenous toxicity studies on indecainide, an antidysrhythmic agent, were conducted in rats and dogs. Rats (10 males, 10 females/group) were given daily intravenous (i.v.) doses of 0, 3, 6, or 9 mg/kg of indecainide for 1 month. 6 Of 10 males and 1 of 10 females given 9 mg/kg died during the test period. All but 2 animals from the other test groups survived. The high end of these daily doses was close to the acute single lethal dose, and the deaths were not unexpected. There were no treatment-related hematologic or serum chemistry changes in the surviving animals. No treatment-related histopathologic changes occurred in any of the animals. Groups of dogs (2 males, 2 females per group) were given daily i.v. injections of 0, 1.5, 3, or 4.5 mg/kg of indecainide for 1 month. 2 Of 4 dogs died after receiving multiple daily doses of 4.5 mg/kg. No treatment-related histopathologic changes were present in these animals. Dogs given doses of 1.5 or 3 mg/kg tolerated daily injections of the compound with no overt signs of toxicity and without hematologic, serum chemistry or histologic changes. Electrocardiograms revealed prolonged PR, QRS, and QT intervals in dogs from all three dose groups. Rats and dogs tolerated daily intravenous doses of indecainide as high as 6 and 3 mg/kg, respectively, with no evidence of any effect of treatment except the expected pharmacological action on the myocardium. PMID- 4035705 TI - Acrylamide alters oxidative enzyme activity in rat motoneurons. AB - Acrylamide (ACR) produces a central-peripheral distal axonopathy, via an unknown mechanism. We have investigated the effects of ACR on the activity of enzymes responsible for the oxidation of NADH (NADH-tetrazolium reductase activity, NADH TR) with quantitative histochemical techniques. Chronic (5- or 10-day) injection of ACR (50 mg/kg/day) resulted in a significant decrease in enzyme activity in soleus motoneurons, which normally have high NADH-TR activity. The NADH-TR activity in motoneurons with low oxidative metabolism was not significantly affected. Retrograde labeling of motoneurons with horseradish peroxidase was diminished by the acrylamide treatment. These data demonstrate an acrylamide induced change in the oxidative metabolism of certain motoneurons; further study will determine whether oxidative metabolism is the primary site of action of ACR in producing the distal axonopathy. PMID- 4035706 TI - Elevation of hepatic metallothionein in rats chronically exposed to dietary ethionine. AB - Following 30 weeks of exposure to 0.3% ethionine in the diet, male Fischer rats bearing liver cell tumors showed a marked increase (9.5 fold) in hepatic metallothionein (MT) concentrations relative to control, as assessed by the cadmium-hemoglobin assay. To confirm the presence of MT in the tumor-containing livers of ethionine-fed rats, biochemical analyses were performed. Spectral analysis of a purified protein from ethionine-treated livers revealed a UV absorption spectrum characteristic of MT. Gel filtration (Sephadex G-75) indicated a prominent copper (Cu) and zinc (Zn)-containing peak with a Mr (approx. 9 000) similar to that of MT. Concurrent with the elevation in hepatic MT in ethionine-fed rats there was an increase in the concentration of Cu and Zn in hepatic cytosol. PMID- 4035707 TI - Splenomegaly in mice following exposure to ambient levels of ozone. AB - Female strain A/J mice were exposed to 0.31 ppm (608 micrograms/m3) ozone continuously for 103 h every other week for 6 mth. Following an additional period of 5 mth in a filtered air environment, animals were killed and examined for evidence of altered spleen weight. It was observed that animals exposed to ozone had a greater spleen weight, and spleen to body weight ratio than air-breathing controls. In some of the ozone-exposed mice, pronounced splenomegaly was noted. Increased spleen weight appears to be another example of an extrapulmonary effect of ozone inhalation. PMID- 4035709 TI - Teratogenic potency of TCDD, TCDF and TCDD-TCDF combinations in C57BL/6N mice. AB - 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) and 2,3,7,8-tetrachlorodibenzofuran (TCDF) cause the same spectrum of fetal anomalies in C57BL/6N mice. Pregnant dams were treated with TCDD, TCDF and combinations of the 2 compounds on gestation day 10, and examined for maternal and fetal effects on day 18. The fetal kidneys were the most sensitive target for teratogenicity. The dose response for cleft palate induction fit the probit model for both compounds, suggesting that TCDD was approximately 30 times more potent than TCDF. The interaction between these 2 compounds was consistent with a model for additive toxicity. PMID- 4035708 TI - Effects of surfactants on the permeability of canine oral mucosa in vitro. AB - The effect of 3 cationic, 1 anionic, and 1 non-ionic surfactant on the permeability of oral frenulum removed from anesthetized dogs was determined in vitro. Permeability to 12 organic compounds was measured in the presence and absence of surfactant. Cetylpyridinium chloride, cetyltrimethylammonium bromide, benzalkonium chloride and sodium lauryl sulfate, at concentrations from 0.025 1.0% caused dose-related increases in permeability to each of the solutes tested, whereas polysorbate 80 caused an increase in permeability to only 3 solutes, and this occurred only at the highest surfactant concentration employed. PMID- 4035710 TI - The toxic and teratogenic effects of selected organophosphorus compounds on the embryos of three species of amphibians. AB - The toxic and teratogenic effects of 4 organophosphorus compounds (phenyl saliginen cyclic phosphate (PSCP), leptophos-oxon (LPTO), tri-o-tolyl phosphate (TOTP), and paraoxon (PXN] were investigated in the embryos of 3 species of frogs. Developmental abnormalities were observed in surviving embryos of each of the 3 species following exposure to PSCP at concentrations as low as 500 ppb for 24 h. LPTO, while being toxic to gray treefrog embryos at concentrations as low as 2.2 ppm, did not induce developmental abnormalities. TOTP and PXN were neither toxic nor teratogenic at concentrations of 10 ppm and 100 ppm respectively. PMID- 4035711 TI - Enzymatic denitrification of 2-nitropropane in uninduced mouse liver microsomes. AB - Hepatic microsomes from 5 strains of untreated mice were tested for the ability to enzymatically cleave the nitro group from 2-nitropropane (2NP). All strains showed significant NADPH-dependent nitrite release at pH 7.6 and pH 8.8. Statistical differences in nitrite-releasing activity between strains were found between BALB and PL/J and ATH strains at pH 7.6. At pH 8.8, BIO.M differed from CD-1 and BALB. These results are in contrast to a report of little or no denitrification activity in uninduced rats and suggest that the 2NP microsomal metabolism may be of greater importance than previously thought. PMID- 4035712 TI - Dimethyl sulfoxide: lack of suppression of the humoral immune response in mice. AB - Mice were injected intraperitoneally (i.p.) with 100% dimethyl sulfoxide (DMSO) or sterile saline (controls) for 36 days. The mice received 0.05 ml daily for one week, 0.025 ml every other day for the second week (because the DMSO-treated mice appeared weak), and 0.05 ml daily for 3 more weeks. All mice were immunized twice with sheep red blood cells (days 13 and 24), and bled twice by caudal incision (days 20 and 29). Hematocrits were significantly decreased (P less than or equal to 0.002) but still within the normal range. The primary and secondary antibody response to sheep red blood cells (SRBC), leukocyte counts, body weight, and the size of the heart, lungs, spleen, thymus, and kidneys were not affected. DMSO treatment resulted in significant liver enlargement (P = 0.02). It is concluded that this dose of DMSO is not deleterious to the humoral immune response in mice responding to a new antigen. PMID- 4035713 TI - Inhibition of 4-aminobutyric acid (GABA) turnover by chlordane. AB - 4-Aminobutyric acid (GABA) turnover was measured in mice 8 h after an acute injection of 1 g/kg of technical grade chlordane in corn oil. Significant decreases in GABA turnover were observed in the cortex, striatum, hippocampus and hypothalamus after chlordane treatment. A smaller, though significant, decrease was also observed in the cerebellum. These results may help to explain the hyperexcitability and convulsions observed after acute high-dose exposure to this compound. PMID- 4035714 TI - Inhibitory effect of various organophosphorus esters on rat liver malathion carboxylesterase in vitro: role of mixed-function oxidases. AB - 6 Structurally related trialkyl phosphorothioates were assessed for their inhibitory effects on rat liver malathion carboxylesterase in vitro. IC50 values indicate that all these compounds, except compound III, a phosphorodithioate, inhibited the activity of the enzyme progressively with increasing incubation time of the compounds with the enzyme preparation. Compounds with an ethyl substitution were more potent than the corresponding methyl-substituted inhibitors. There was cytochrome P-450-mediated oxidative deactivation of all compounds tested, this was especially profound with inhibitors containing an ethyl thiolate moiety. PMID- 4035716 TI - Detection of impervious tissue in tree bark with selective histochemistry and fluorescence microscopy. AB - Use of conventional histochemical tests in conjunction with fluorescence microscopy has validated the concept of impervious tissue in the bark of trees. Application of phloroglucinol + HCl or toluidine blue O selectively quenched lignin autofluorescence and allowed visualization of intracellular suberin lamellae previously undetected. Fluorescence of intracellular lamellae was quenched with Sudan black B and enhanced with Sudan IV thus providing evidence for the suberized nature of a tissue heretofore regarded as nonsuberized. PMID- 4035715 TI - Comparative disposition and elimination of chlordane in rats and mice. AB - The absorption, distribution and elimination of orally administered cis [14C]chlordane (1.0 mg/kg) was determined in male Sprague-Dawley rats and C57BL/6JX mice. Absorption appeared somewhat slower in mice, but total [14C]chlordane equivalents at peak blood concentration (113 ng/ml at 8 h) exceeded the maximum which occurred in rats (81 ng/ml at 2 h). Peak tissue residues in both species were observed within 4 h, suggesting that the radiocarbon responsible for the latent peak blood levels in mice was eliminated rather than sequestered by the tissues. This was supported by the findings that peak tissue residue levels were lower in mice, and that the initial fecal elimination rate was higher than in rats. At 12 h, 34% and 7% of the doses were excreted in mouse and rat feces, respectively; by 3 days, both species had voided 83% of the dose in the feces. Clearance rates of tissue residues were markedly faster in the rat, and consequently, the total body burden resulting from chronic exposure to chlordane will be far greater in mice than in rats. PMID- 4035717 TI - Microtome blade holders for cryostats. PMID- 4035718 TI - A glass knife tool for cutting 50-micron sections for electron microscopic cytochemistry. PMID- 4035719 TI - VIIth meeting of the European Society for Hyperthermic Oncology (ESHO). Paris, September 16-18, 1985. Abstracts. PMID- 4035720 TI - [The first linear electron accelerator Therac 15-Saturne in clinical service. 2. Measurement of electron radiation]. AB - Therac 15-Saturne is a linear accelerator for photon and electron radiation with a double scattering screen system. It has proved its worth during more than three years of clinical use. The dosimetric data of both kinds of radiation correspond to the international requirements for modern therapy units. The trimmer system for electron radiation is equipped with a continuous field size adjustment device for the whole range of field sizes. Thus a fast and precise adjustment is possible without any changing of tubes. PMID- 4035721 TI - The impact of development and population policies on fertility in India. AB - This article examines the impact of development and population policies on fertility decline and regional variations in India during the 1970s. Indicators of development at the household level include female literacy and education, infant mortality, and poverty; at the village level they include availability of such social services as schools, medical facilities, and transportation and communication facilities. Multiple regression analysis of data aggregated at the state level demonstrates that conditions conducive to fertility decline include high adult female literacy and low infant mortality as indicators of social development, and high contraceptive use and, to a lesser extent, high female age at marriage as proximate determinants of fertility. There are reasons to believe that India's national family planning program contributed to the decline in fertility observed since the 1960s. The pace of fertility decline in the future will depend upon the pace of infant mortality decline, enhancement in female education, and improvements in family planning programs. PMID- 4035722 TI - Family size intentions and socioeconomic status in Singapore, 1974-1981. AB - Singapore has in recent years undergone a tremendous fertility decline that has affected couples at all socioeconomic levels. Using representative biographical sketches, this article presents the results of a panel study on family planning intentions and behavior among 45 young Chinese Singaporean couples. The couples, ranked as average or affluent working-class, or middle-class, were first interviewed in 1974-76 and were followed up in 1981. The study compares early childbearing intentions with actual childbearing behavior, examining the motivation for childbearing by socioeconomic group and highlighting the differences found. The follow-up interviews reveal that, on average, all couples in the sample bore 0.4 fewer children than originally intended. The motivation for changed childbearing intentions, however, differed according to socioeconomic status and the perceived role that children play in the family economy. PMID- 4035723 TI - Sex education laws and policies. AB - Sex education laws and policies are important in facilitating or blocking efforts to provide adolescents with sexuality education and information. Legislation in developing and industrialized countries concerns both sexuality education in schools and adolescents' access to information on contraception and abortion. Although laws and policies vary, the trend is to remove laws restricting sex education and information and to promote the flow of reproductive health information for adolescents. The integration of sex education with programs that provide contraceptive services offers the promise of preventing unwanted pregnancy in adolescents, with its all too frequent tragic health and social consequences. PMID- 4035724 TI - The effect of previous child death on infant and child mortality in rural Nepal. AB - Data from the Nepal Fertility Survey 1976, which was carried out by the Nepal Family Planning and Maternal-Child Health Project in collaboration with the World Fertility Survey, is used to explore the interrelationships of sibling mortality. Even when demographic variables are considered, the risk of infant and child death is considerably higher among children of mothers whose previous child died than among those whose previous child survived. An attempt is also made to examine whether it is because of close birth spacing or because of the family environment that the previous child loss puts the subsequent children at an excessive risk of dying during infancy and childhood. PMID- 4035725 TI - Abnormal stem cells in autoimmune-prone mice are responsible for premature thymic involution. AB - Autoimmune-prone mice show premature thymic involution, including morphological and functional abnormalities. To determine why the thymic abnormalities develop in autoimmune-prone mice, transplantation of the thymus and/or bone marrow was performed. When thymuses of newborn MRL/1 (H-2k) mice were grafted into C3H/HeN nu/nu(H-2k) mice, the engrafted thymuses did not show the abnormalities which characterize the thymus in the autoimmune-prone MRL/1 mice. By contrast, when thymuses of newborn C3H/HeN or MRL/n mice were grafted into MRL/1 mice, the engrafted thymuses developed after an interval of 3 months the same morphological abnormalities as were seen in MRL/1 mice. Thus, we can conclude that premature involution of the thymus in autoimmune-prone mice may not be a genetically determined abnormality intrinsic to the thymus, but rather an abnormality secondary to other events occurring in these mice. When bone marrow of young C3H/HeN nu/nu mice was transplanted into irradiated (850 rad) MRL/1 mice, neither thymic abnormalities nor autoimmune diseases developed. Therefore, it seem likely that abnormal stem cells in autoimmune-prone mice induce thymic abnormalities, and these, in turn, are associated with the development of autoimmune diseases. PMID- 4035726 TI - Water related diarrhoeal diseases and infant mortality and morbidity. Symposium. PMID- 4035727 TI - Simultaneous determination of pyrimethamine and sulphadoxine in human plasma by high-performance liquid chromatography. AB - Pyrimethamine was extracted as a base, and sulphadoxine simultaneous as an ion pair with tetrabutyl-ammonium into methylene chloride. After re-extraction into an acidic aqueous phase separation of the drugs was performed by reversed-phase high performance liquid chromatography using Nucleosil C-18 as the support and acetonitrile-phosphate buffer pH 5.5 (28 + 72) as the mobile phase with tetrabutyl-ammonium as counter ion. Photometric detection at 240 nm was used for both substances. The within-day precision of the method was 5 to 10% for pyrimethamine within 50 to 1000 nmol/l (13 to 250 ng/ml) and for sulphadoxine 3 to 6% within 50 to 1000 mumol/l (16 to 310 micrograms/ml) in plasma. The method is suitable for simultaneous determination of plasma levels of pyrimethamine and sulphadoxine after therapeutic doses of Fansidar. PMID- 4035728 TI - Natural hosts of Leishmania mexicana amazonensis Lainson and Shaw, 1972 (Kinetoplastida: Trypanosomatidae) in French Guiana. PMID- 4035729 TI - Isotope renography and urinary schistosomiasis: a study in a Gambian community. AB - A transportable apparatus for isotope renography, which allowed deconvolution analysis, was used to study the prevalence and prognosis of abnormalities associated with urinary schistosomiasis. Before carrying out studies in a heavily infected community, observations were made in a non-endemic area to allow derivation of criteria for abnormality. Comparison of the findings in the two areas showed that changes suggesting urinary tract obstruction were more common in the endemic area in subjects between nine and 45 years but not in older subjects. Measurements of effective renal plasma flow showed renal function was impaired in the endemic area in subjects older than 17 years but not in younger subjects. In the endemic area the results of renography were unrelated to the urinary egg count of the subjects examined, but there was an improvement in the abnormal renograms in a group of subjects aged between nine and 20 years who were re-examined a year after treatment with metrifonate. Follow-up data about 316 subjects was obtained two years after renography. Nine subjects had died, including four of the five subjects with abnormalities suggesting both obstruction and over-all loss of renal function. These findings, which are comparable to the results of similar studies using radiological techniques, suggest urinary schistosomiasis may be a significant cause of mortality in adults in intensely infected communities. PMID- 4035730 TI - Fibroblast stimulating activity of extracts of hepatic granulomata of Schistosoma mansoni-infected rodents with marked or slight hepatic fibrosis. AB - Eight weeks following infection with Schistosoma mansoni ICR strain mice showed much more marked hepatic fibrosis than did C57BL/6 mice or hamsters. None the less, extracts of the hepatic granulomata of these animals had similar fibroblast stimulating activity when assayed in vitro. PMID- 4035731 TI - Post-infective malabsorption in the temperate zone. AB - A series of 37 adults normally resident in Britain have been investigated for persistent bowel symptoms following acute enteritis. 26 had intestinal malabsorption, of whom 12 had been travelling in the Mediterranean area, whereas 10 developed their illness at home. Mild jejunal mucosal abnormalities were found in cases with and without malabsorption, and the intraepithelial lymphocyte count correlated more closely with the degree of malabsorption than did the histological grading. Over 80% of severe cases were folate deficient. Enterobacteria were cultured from the jejunal fluid in 30% of cases. Our observations confirm that post-infective malabsorption occurs sporadically in adults in the temperate zone and is occasionally severe. The condition involves small bowel contamination with enterobacteria, and it differs from acute tropical sprue only in its greater tendency to spontaneous recovery. PMID- 4035732 TI - Studies on the biology of Simuliidae (Diptera) at the Santiago onchocerciasis focus in Ecuador, with special reference to the vectors and disease transmission. AB - A survey showed the presence of seven simuliid species in the onchocerciasis focus in Ecuador Simulium exiguum and S. quadrivittatum were the two most common anthropophilic species and were shown to be both experimental and natural vectors of Onchocerca volvulus. S. antillarum only occasionally bit man. Observations were made on the biology of the two vector species and it was evident that S. exiguum was the primary vector of onchocerciasis in the rainy season. The relevance of these findings to the epidemiology and control of onchocerciasis in Ecuador are discussed. PMID- 4035733 TI - Histopathology of hepatic amoebiasis in guinea-pigs infected through intracaecal and intramesenteric routes. AB - The comparative histopathological details of amoebic liver abscess were studied following intracaecal and intramesenteric inoculation of Entamoeba histolytica into guinea-pigs. The histological changes of amoebic liver abscess formed via the former route were similar to those seen in man. These consisted of a central necrotic area with few lymphomononuclear cells and E. histolytica trophozoites at the periphery of the lesion. The amoebic liver abscess formed via the intramesenteric route, however, differed from that formed by intracaecal inoculation in three ways: (i) in having an intense inflammatory reaction, (ii) healing of the abscess by fibrosis and (iii) exhibiting a giant cell reaction. PMID- 4035735 TI - Toxocara canis larvae in the brain of a British child. AB - The clinical and autopsy findings of a two and a half year-old infant with Toxocara sp. infection of the brain and granulomatous lesions in the liver are reported. The cause of death was non-accidental injury. The relationship between Toxocara infection and behavioural disorders is discussed. PMID- 4035734 TI - ELISA using intact promastigotes for immunodiagnosis of kala-azar. AB - The commonly used diagnostic methods for visceral leishmaniasis (kala-azar) have many disadvantages. ELISA appears to be a more easily applied test for diagnosis, follow-up of treatment and epidemiology. The preparation of the ELISA antigen has given rise to difficulties in standardization since these are usually soluble. Intact cultured promastigotes have been used to develop an ELISA which is sensitive and specific while avoiding the extra handling which is a source of variability and lack of reproducibility. When tested on sera from kala-azar patients and patients with other tropical diseases, this ELISA was able to detect specific antibodies at very high serum dilutions. It is thus promising as a screening method applicable in the field. PMID- 4035736 TI - Provocation of poliomyelitis by multiple injections. AB - Injections of vaccines provoked paralytic poliomyelitis in children in the UK and elsewhere. The effect of multiple injections has not been recognized previously but could be important in the tropics where children receive many injections. A number of epidemics of poliomyelitis between 1914 and 1962 are related to children with congenital syphilis or yaws under treatment with arsenicals or penicillin. Rates of 25% of children with paralysis occurred in epidemics while in non-epidemic periods the increase in susceptibility was about 25 fold. Other possible cases of provocation are discussed. Although in the tropics injections before paralysis may be causal, it will be difficult to prove that they are not coincident. The very high rate of paralysis following multiple injections is powerful evidence that injections in the tropics are often causal. PMID- 4035737 TI - The adherence of Giardia lamblia trophozoites to nylon fibre microcolumns: effect of temperature, fluoride, cyanide and metronidazole. AB - A simple rapid method for the measurement of adherence of Giardia lamblia trophozoites is described. Microcolumns are prepared from 10 mg amounts of nylon fibre packed into 100 microliter size disposable pipette tips. The kinetics show that 30 min is the optimum contact time for the experiments. Maximum adherence occurred at 37 degrees C, minimal at 4 degrees C, and intermediate at 25 degrees C, suggesting that adherence is an energy-dependent process. Adherence was fluoride-sensitive but cyanide-insensitive, suggesting that this parasite derives its energy from the glycolytic pathway, and not the oxidative pathway. Metronidazole, one of the mainstays for chemotherapy of giardiasis, produced significant inhibition of adherence at 10 micrograms/ml and 100 micrograms/ml concentrations after one hour pre-incubation. PMID- 4035738 TI - Fingers or spoons to make oral rehydration solution? AB - The accuracy and variability of the composition of oral rehydration solution (ORS) prepared by village health workers using (i) a finger measurement technique and (ii) a special ORS measuring spoon were compared. The sodium and sucrose concentrations were measured in 130 ORSs prepared by each technique. All the spoon-measured ORSs had acceptable levels of sodium and sucrose, compared with 93% of the finger-measured ORSs. Only 2.3% of finger-measured ORSs had hypertonic sodium levels. The variability of sodium and sucrose levels was significantly greater with the finger measurement technique. This comparison should assist programme managers to decide which technique to adopt. Both techniques require careful instruction to ensure accuracy. PMID- 4035739 TI - Egg count variability and sensitivity of a thin smear technique for the diagnosis of Schistosoma mansoni. AB - Variation in daily egg counts, and in counts for samples of the same stool, was investigated in children with Schistosoma mansoni and Ascaris lumbricoides infections, using a thin smear technique. The results indicated that counts vary according to the stool consistency; drier stools from the same person producing up to seven times greater counts than wet ones. The sensitivity of the technique was tested in schoolchildren living in an endemic S. mansoni area, and found to detect all infections with intensities of greater than 50 eggs per gram of stool, after examination of only one slide containing 40mg stool. The sensitivity varied with the intensity of infection. The relevance of these findings to diagnosis in field situations is discussed. PMID- 4035740 TI - Blood pressure patterns in relation to age, weight and urinary electrolytes in three Kenyan communities. AB - The blood pressure patterns of three Kenyan communities have been studied: 861 members of the Luo tribe in a rural community, 281 members of the Kamba tribe in a rural community and 310 "urban" Luo living in Nairobi. The slope of linear regression of blood pressure with age was significantly different in each population: rural Luo had the smallest rise with age and urban Luo had the largest rise with age, while the Kamba tribe were in between. The differences could not be accounted for by weight. Urinary electrolyte data showed rural Luo had the lowest sodium ratios (sodium/creatinine, sodium/potassium) and the highest potassium/creatinine ratio: urban Luo had the highest sodium and lowest potassium ratios and rural Kamba had values in between. The differences in blood pressures between the two groups of the same tribe in different environments (rural and urban Luo) were far greater than those between different genetic groups (Kamba and Luo) underlining the importance of environmental factor(s) in the determination of arterial pressure. Furthermore, these data support the theory that the dietary intake of sodium and potassium are the major influential environmental factors affecting blood pressure. PMID- 4035741 TI - Immunity after treatment of human schistosomiasis mansoni. II. Identification of resistant individuals, and analysis of their immune responses. AB - Intensities of re-infection were monitored at three-monthly intervals after treatment of Schistosoma mansoni infections in a group of 119 Kenyan schoolchildren, whose levels of water contact were also observed. 22 children showed high reinfection intensities (greater than 100 eggs per gram of faeces) by 12 months after treatment, and were considered to be susceptible. Out of 70 children who showed low reinfection intensities during the same period (less than 30 eggs per gram), 35 showed high levels both of total water contact and of contact with sites containing infected snails. In these children, the relative lack of reinfection could not be attributed to a lack of exposure, and they were classified as resistant to reinfection. Comparison of the two groups, resistant and susceptible, revealed no difference in pretreatment intensities of infection. However, there was a marked difference in age, the mean age of the resistant group being two years greater than that of the susceptible group, within a restricted starting age range. These findings indicated that resistance was an acquired and age-dependent phenomenon, not obviously related to previous egg induced pathology. Studies of immune responses revealed no clearcut correlate of resistance, but there were interesting differences between the two groups. Whereas anti-egg antigen responses declined after treatment to a greater extent in the resistant than in the susceptible group, antibodies mediating eosinophil dependent killing of schistosomula rose markedly in both groups, strongly suggesting that the resistant children were being exposed to cercariae. Anti adult worm antibodies rose sharply in both groups immediately after treatment, and thereafter declined to pretreatment levels. Although some individual children showed high levels of IgE anti-schistosomulum antibodies, there were no significant differences between the two groups. Since all children showed detectable levels of antibodies mediating eosinophil-dependent killing of schistosomula, the possibility was considered that such antibodies might be a necessary, but not a limiting, factor in immunity. Instead, the functional state of the effector cells mediating antibody-dependent killing might be limiting. Eosinophil levels, measured as an indirect estimate of eosinophil functional activity, did not differ between the two groups. There were, however, marked differences between different individuals in their capacity to produce eosinophil stimulating monocyte mediators, and although this cannot yet be related to resistance, this aspect is worth further study.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 4035742 TI - The portable Nabarro weight-height anthropometric nutrition assessment chart. A field trial in three countries in Africa. AB - A cluster sampling technique and a portable weight-for-height measuring chart were used to conduct nutrition surveys on children between 12 and 60 months of age in rural communities in Tanzania, Zambia and Zaire. Wasting was uncommon. Only four (0.6%) of 644 children who were weighed and measured had a weight-for height of less than 80% of the standard. The new chart classified all of these as wasted, along with five others whose weight-for-heights were close to 80% (80.2 to 83.3%). The portable weight-for-height chart works well, and the observer error was small. Compared with calculations from tables it did not fail to identify any of the significantly wasted children and gave five false positives, all in borderline cases. Simple modifications would make this chart easier to use. PMID- 4035743 TI - Blackfly bites, onchocerciasis and leopard skin. PMID- 4035744 TI - Isolation of Japanese encephalitis virus strains from sentinel pigs in northern Thailand, 1982. PMID- 4035745 TI - Leishmaniasis or AIDS? PMID- 4035746 TI - Cryptosporidium in stool specimens in Madrid. PMID- 4035748 TI - Depth of penetration of mammalian skin by sandflies. PMID- 4035747 TI - Experimental transmission of Trichuris ova from monkeys to man. PMID- 4035750 TI - Amoebiasis in Kashmir (India)--a laboratory study. PMID- 4035749 TI - Lone laryngeal leishmaniasis. PMID- 4035751 TI - Supernatant fluid inhibiting the incorporation of [3H]-thymidine by rabbit splenic lymphocytes stimulated in a variety of in vitro assays. PMID- 4035752 TI - Control values of lymphocyte subsets in healthy volunteers. PMID- 4035753 TI - Practising in the tropics. PMID- 4035755 TI - Simplified management of fluid and electrolyte problems. 2--Assessment of treatment, complications, and central venous pressure. PMID- 4035754 TI - Anal fissures, abscesses and fistulae. Alternatives in the management of common anorectal conditions--2. PMID- 4035756 TI - Cataract surgery. PMID- 4035757 TI - Management of rupture of the gravid uterus. PMID- 4035758 TI - Child health card. PMID- 4035759 TI - Immunization of sick children. PMID- 4035760 TI - Utilization of health personnel in dental health activities in Nigeria. PMID- 4035761 TI - Use of beans diet for control of diabetes. PMID- 4035762 TI - Successful continuous ambulatory peritoneal dialysis in tropical Africa. PMID- 4035763 TI - Are we missing cases of onchocerciasis? PMID- 4035764 TI - An inexpensive ophthalmoscope. PMID- 4035765 TI - Volvulus of sigmoid colon. PMID- 4035766 TI - Abdominal pregnancy. PMID- 4035767 TI - Successful abdominal pregnancy. PMID- 4035768 TI - Training programme for rural midwives in Mozambique. PMID- 4035770 TI - Physical restraint of the disturbed patient. PMID- 4035769 TI - Hepatitis B markers in patients with and without ascites in Haiti. PMID- 4035771 TI - Prospects of human malaria and Bancroftian filariasis infections in the Lower Rufiji Basin, Tanzania. I. Malaria. AB - Surveys for human malaria infections were conducted in the Lower Rufiji Basin in Tanzania, before and after the long rains in 1981. A multipurpose water resources development project has been planned in the area. Overall asexual malaria parasite, gametocyte and spleen rates of 38.6%, 3.8% and 21.1% respectively were observed before the long rains whilst respective parameters after the long rains were 44.5%, 2.8% and 17.3%. Malaria parasite species percentages of 95.5, 1.0, 0.2 and 3.4 were observed in respect of P. falciparum, P. malariae, P. ovale and mixed infections respectively for both periods. Malaria endemicity in the Lower Rufiji Basin ranges between mesoendemic to hyperendemic. Following implementation of the project, malaria is likely to become holoendemic. PMID- 4035772 TI - Schistosomiasis haematobium and the mortality occurring in an endemic community at Bujashi, Tanzania. AB - A population of 4516 inhabitants of an area endemic for schistosomiasis haematobium at Bujashi, Tanzania, was investigated in 1983 seven years after a baseline study for a pilot control project to determine the disease mortality risk. The distribution of the 238 deaths occurring in the population, when analysed by the Mantel Haenszel test, showed similar age and sex specific mortality rates among the 2309 non-cases and 2109 cases found excreting schistosome eggs at the baseline urine examinations. Furthermore, the respective follow up 36 and 57 cases with and without urological sequelae on the baseline excretion urograms, also showed similar age adjusted mortality rates as did the 1663 and 446 metrifonate treated and untreated cases respectively. The findings suggested, therefore, that neither the disease nor its treatment affected the mortality occurring in the population. PMID- 4035773 TI - Probable hybridization between S. intercalatum and S. haematobium in western Gabun. AB - Cases of intestinal schistosomiasis due to S. intercalatum were compared in an area of high prevalence of S. haematobium (Palmeveas) with those in an area of low prevalence of S. haematobium (Lambarene) in the Gabon. The patients with intestinal schistosomiasis in the area with high prevalence of S. haematobium excreted more eggs resembling S. intercalatum in the urine than those in the low S. haematobium prevalence area. It is suggested that the eggs resembling morphologically S. intercalatum might be hybrids between S. intercalatum and S. haematobium. PMID- 4035774 TI - Prevalence of latent iron deficiency in patients with chronic S. mansoni infection. AB - The iron status of 103 male patients aged 19 to 48 years with chronic S. mansoni infection was evaluated before treatment. Fasting blood samples were analyzed for serum ferritin and iron, percent transferrin saturation, hemoglobin and other hematological indices. Anemia based on hemoglobin level of less than 13 gm/dl was found in 52 patients. Of the remaining 51 nonanemic patients 10% would be classified as iron deficient by serum iron, 31% by percent transferrin saturation and 83% by serum ferritin. Schistosomal liver involvement in some of these patients did not cause any significant difference in the mean serum ferritin levels between this group of patients and those with no liver involvement. These findings suggest that serum ferritin is a valid and sensitive test for detecting iron deficiency in these patients and that chronic S. mansoni infection is associated with high incidence of latent iron deficiency. PMID- 4035775 TI - The prevalence of intestinal parasites in two suburbs of Kinshasa (Zaire) and their relation to domestic water supplies. AB - The prevalence of common intestinal nematodes (Ascaris, Trichuris and hookworms) and protozoa (Entamoeba coli, E. histolytica, Giardia, Trichomonas) was compared in two suburbs of Kinshasa, one provided with piped water and the other one with wells. Pit latrines were used in both places. No significant differences were observed for the worms, but the prevalence of the four common protozoa was approximately twice as high in the community without piped water supply. It is concluded that providing piped water has some impact on the transmission of potentially pathogenic intestinal protozoa, but no influence, at least on the short run, on intestinal worms. Infections with Giardia and Trichomonas were significantly associated. PMID- 4035776 TI - Mycetoma in northern Nigeria. AB - Fifteen cases of mycetoma were studied during a period of eight years (1976 to 1984) at Ahmadu Bello University Teaching Hospital, Zaria, Nigeria. The commonest aetiological agent seen was Nocardia; the actinomycotic mycetoma was more prevalent as compared to maduromycotic mycetoma. PMID- 4035777 TI - Dapsone resistant leprosy, the western Kenya experience. AB - 41 patients out of 804 registered lepromatous (LL) and borderline lepromatous (BL) patients were studied for possible dapsone resistance by series of biopsy specimens, skin smears and clinical examination. These patients were drawn from a pool of 4384 registered leprosy patients in the west Kenya Leprosy Control Project area. Six out of fourty one cases (14.6%) were confirmed as dapsone resistant by series of biopsy specimens taken when patients were on supervised dapsone therapy; 11 patients (26.8%) were suspected to be resistant and 24 patients (58.6%) responded well to dapsone therapy. All the confirmed cases were lepromatous leprosy cases. We therefore found that there is dapsone resistance here with a maximal prevalence rate of 7 per 1000 in all lepromatous cases and 14.6% in clinically suspicious cases. PMID- 4035778 TI - Non-invasive cardiac study in diabetic Nigerians using systolic time intervals. AB - Non-invasive cardiac studies using systolic time intervals were performed on 89 diabetic Nigerians and 45 non-diabetic controls, to investigate possible preclinical abnormality of left ventricular function. There was no significant difference in the pre-ejection period to left ventricular ejection time ratio (PEP/LVET) between the patients and controls: 0.373 +/- 0.011 vs 0.365 +/- 0.013 (P = 0.688). Patients at higher risk for developing significant vascular disease i.e. those with peripheral vascular insufficiency, those in higher socio-economic class and those with disease duration of 10 or more years had the highest mean values of PEP/LVET (0.403, 0.403 and 0.412 respectively). However, these values did not reach a level of significance. There was no correlation between PEP/LVET and age, body mass index, duration of diabetes, total or HDL cholesterol and the HDL to total cholesterol ratio. Because recent reports have related diabetic cardiomyopathy to angiopathic disease in diabetes, these results suggest that Nigerian patients, who like most other black African diabetics show little susceptibility to severe vascular complications of diabetes may enjoy some protection from a preclinical abnormality of left ventricular function as well. PMID- 4035779 TI - Peptic diseases in Ethiopia: a prospective analysis of 200 endoscopically proven cases. AB - The clinical features of 200 Ethiopian patients with endoscopically confirmed duodenal ulcer were studied according to a prospectively formulated protocol. The peak age incidence of duodenal ulcer is between 30 and 40, about 10 years younger than in the Western world. Unlike reports from other parts of Africa, the male to female ratio is 3:1 and the commonest complication is haemorrhage and not pyloric stenosis. Gastric ulcers and stomal ulcers are rare. Forty-eight per cent of 80 patients, whose blood groups were determined, are "O" positive and 30% "A" positive. The diagnostic value of aggregates of classical signs and symptoms, barium meal and the fibreoptic endoscopes are discussed in detail. PMID- 4035780 TI - Fractured hips in rural Melanesians: a nonepidemic. AB - Fractured hips are increasingly common in elderly citizens of many developed countries. Such fractures seem to be rare in less affluent people of some developing countries, even amongst the elderly. A four year review was done of all trauma patients admitted to a provincial hospital in hospital in Papua New Guinea which serves 135.000 people living mainly in remote hamlets. Only three fractures of the proximal femur were noted. One of these was in a bedridden plantation owner. Not a single fracture of the femoral neck was noted in the Melanesian population. Colles fractures of the distal radius were also rarely seen. Other fractures were common. Elderly Melanesian villagers are physically active, and it appears that this is an important factor in preventing bone weakness and associated fractures of the hip and distal radius. Modern cities and urban lifestyles need radical change to keep elderly people more physically active. PMID- 4035781 TI - Intestinal obstruction of infancy and childhood in Benin City, Nigeria. AB - The pattern of intestinal obstruction observed on 168 Nigerian infants and children is presented. The commonest causes of intestinal obstruction were intussusception (21%), anorectal anomalies (20%) and Hirschsprung's disease (14%). Strangulated hernia and adhesions occurring in 3.5% and 1.7% of cases respectively were notably uncommon in this age group. The role of radiology in the management of some cases is highlighted. PMID- 4035782 TI - Malignant bone tumours, experience at King Fahd University Hospital Al-Khobar, Saudi Arabia. AB - Reports show striking regional and ethnic variations in the incidence and pattern of certain malignancies in the Middle East. In view of this, a study of 19 cases of malignant tumours of the bone seen at King Fahd University Hospital during the period 1981-1983 was carried out. Of these eight were primary and eleven secondary tumours. Lymphoma and Ewing's sarcoma formed 50% of the primary tumours. Breast and lungs were the chief sources of secondary deposits in the bone. PMID- 4035783 TI - Renal amyloidosis in Jordan. AB - Twenty cases of renal amyloidosis were observed among 182 patients who underwent kidney biopsy at Jordan University Hospital (JUH) during the period 1979-1983. Eight cases were classified as primary amyloidosis while the remaining 12 were secondary to various underlying diseases, the most significant one was familial Mediterranean fever (FMF). Comparison of incidence of renal amyloidosis in kidney biopsy series from neighbouring countries is presented. PMID- 4035784 TI - Plasma vitamin E (alpha tocopherol) levels in normal children and in epileptic children with and without anticonvulsant drug therapy. AB - Plasma alpha tocopherol was assayed in 308 apparently normal children, epileptic children not on anticonvulsants, and anticonvulsant-treated epileptic children. The age range of the subjects was 5 to 12 years and both sexes were equally represented in each group. Plasma alpha tocopherol levels were significantly (p less than 0.001) lower in the anticonvulsant-treated epileptic children than either of the other groups. The values in all groups were lower than published values for adults. No difference in plasma alpha tocopherol values was attributable to sex. The lower plasma alpha tocopherol value in the anticonvulsant-treated epileptic children is probably related to the drug therapy. PMID- 4035785 TI - Serum calcium and protein levels in pregnant African and Caucasian women. AB - Serum calcium and protein concentrations were determined for 243 pregnant urban African and 150 Caucasian women covering the three trimesters of pregnancy. It was shown that the serum protein content of the pregnant African was consistently lower than that of her Caucasian counterpart, probably as a result of environmental and nutritional factors. On the other hand, there appeared to be little difference in the serum calcium concentration of both groups up to the end of the second trimester; thereafter, the serum calcium of the pregnant African began to increase significantly above that of the Caucasian up to term (without hypercalcaemia), whereas the Caucasian calcium concentration remained virtually unchanged. It is therefore concluded that this phenomenon is a compensatory mechanism through which the increasing need of the foetus for calcium was adequately satisfied by mobilization of calcium from its depot. PMID- 4035786 TI - The urban volunteer programme in Dhaka: a community based primary health care and research initiative. AB - In response to a recognition that existing health facilities could not adequately reach the poorer sections of Dhaka city, the International Centre for Diarrhoeal Disease Research, Bangladesh (ICDDR,B) established the Urban Volunteer Programme in 1981. This paper describes the primary health care and research activities of this program and suggests that such an approach can be and should be used in other urban areas of developing countries. PMID- 4035787 TI - Actinomycosis of the liver. AB - We present our first case of actinomycosis in Trinidad and we believe this is also the first reported case of hepatic actinomycosis in the West Indies. PMID- 4035788 TI - Mesenteric venous thrombosis and oral contraceptive use. AB - A case of mesenteric venous thrombosis in a young woman receiving oral contraceptives is reported. This is the first case encountered in the Caribbean region. PMID- 4035789 TI - Cavernous sinus thrombosis in two Papua New Guineans. AB - Bilateral cavernous sinus thrombosis developed following minor forehead abrasions in two adult Melanesians in Papua New Guinea. In both cases diagnosis and the institution of appropriate treatment were delayed. The first patient died but the second survived with residual 6th cranial nerve palsy. Whenever this condition is suspected, because of the high case fatality rate, high-dose, intravenous antibiotic treatment which should include an agent effective against penicillinresistant staphylococci should be commenced without delay pending further investigation. PMID- 4035790 TI - [Resistance of liposomes with different physico-chemical characteristics to the effect of plasma]. AB - The chemical composition, liquid content sign and value of charge as well as structure and size of lipid vesicles are studied for the effect they exert on the liposome permeability for 22Na+ in the presence of human blood plasma. The rate of the isotope outlet from the electroneutral lecithin liposomes is determined by the size of vesicles and the quantity of phospholipid bilayers in their membrane. The presence either of a negative or a positive charge on the surface of the liposome membrane has no essential effect on the outlet rate of the radioactive marker. Introduction of different amounts of cholesterol or sphingomyelin into the liposome composition decreases considerably the lipid vesicle permeability and an increase in the liquid content of their membranes due to the temperature elevation is accompanied by a sharp rise in the isotope outlet rate. A conclusion is drawn on the possibility to control the outlet rate of the liposome content in the presence of blood plasma. PMID- 4035791 TI - [Physico-chemical properties of lysyl-tRNA-synthetase from the rat liver]. AB - Two lysyl-tRNA-synthetase forms are obtained from the rat liver. Their molecular masses are determined by electrophoresis and gel-filtration on Sephadex G-150: form I-122, form II-64 kDalton. Gel-electrophoresis in the presence of 0.1% SDS indicates that form I of lysyl-tRNA-synthetase consists of two subunits with a molecular mass of 64 kDalton each, i. e. it is a dimer. Optimal conditions and kinetic parameters (Km and Vmax) of aminoacylation for the both enzyme forms are similar. Amino acid composition, fluorescence parameters and thermal inactivation conditions are determined. PMID- 4035792 TI - [Study of the subunit structure of catalase from Penicillium vitale]. AB - A molecule of Penicillium vitale catalase is shown to dissociate into subunits with the molecular weight 75-80 kDalton. When hemin is splitted off the molecule also disintegrates into subunits equalling 1/4 of the enzyme molecule. The amino acid composition and fingerprints of the catalase subunits were studied. It is supposed that N-terminal residue of the subunit is blocked. PMID- 4035793 TI - [Effect of blood components on the stability of liposomes]. AB - The human blood plasma is studied for its effect on the outlet of different substances from lecithin liposomes. It is shown that in the presence of the whole blood the permeability of liposomal membrane for the low-molecular weight compounds increases sharply. Blood plasma proteins play a key role in this process but the influence of albumin, gamma-globulins, fibrinogen as well as of serum lipases is rather insignificant. An increase in the rate of outlet of substances in the presence of blood plasma depends on their molecular weight and may be explained by the formation of dynamic defects or pores of definite size in the liposomal membrane. The formation of these defects (pores) is supposed to proceed due to insertion of blood plasma proteins into the phospholipid matrix of liposomes. PMID- 4035794 TI - [Effect of NADH on the catalytic function and reactivity of thiols from rabbit muscle aldolase]. AB - NADH has a corresponding binding site in aldolase, and can activate the reaction of the aldole cleavage of the substrate (fructose-1,6-bisphosphate). Unlike the considerable protection by the substrate, the similar effect of NADH on the sulphydryl enzyme groups is less pronounced, and may be attributed to single cysteine residue. The functionally related and spatially separated binding sites for NADH and substrate are suggested. PMID- 4035795 TI - [Combined effect of adenosine and papaverine on the metabolism of adenine nucleotides in rat thymocytes]. AB - It is shown that in [14C]adenine-labelled thymocytes adenosine increases the content of adenine nucleotides and simultaneously accelerates their catabolism. Papaverine induces acceleration of splitting and a decrease of the specific ATP radioactivity but increases the AMP content and its specific radioactivity. The both effectors intensify considerably the outlet of total radioactive label from cells. If the papaverine effect in the extracellular medium results in accumulation mainly of hypoxanthine in the extracellular medium then the adenosine presence causes accumulation of inosine and hypoxanthine approximately in equal amounts. The release of labelled adenosine from thymocytes in all cases is an insignificant part of extracellular radioactivity. A conclusion is drawn that under conditions of the combined action of the substances under study papaverine removes the adenosine effect caused by its under study papaverine removes the adenosine effect caused by its phosphorylation with the formation of ATP and exerts the dose-depended action on adenine nucleotide metabolism in thymocytes. PMID- 4035796 TI - [Alpha 2-antiplasmin in bovine plasma]. AB - Bovine and human blood plasma contains alpha 2-antiplasmin which possesses affinity to lysin-binding sites in plasmin and inhibits the human plasmin. Its isolation was conducted for two stages: separation of plasminogen on lysin cellulose, fractionation by ammonium sulphate, desalination on molselector G-25, chromatography on DEAE-Sephadex A-50 and affinity chromatography on plasmin sepharose with the blocked active site. PMID- 4035797 TI - [Incorporation of radioactive phosphorus into creatine phosphate of the rabbit myocardium in experimental coronary insufficiency]. AB - It is shown that under conditions of experimental limitation of coronary blood flow in rabbits the intensity of radioactive label (32P) incorporation into creatine phosphate lowers essentially. This evidences for inhibition of creatine phosphorylation in mitochondria under ischemia due to a decrease in the activity of a mitochondrial isoenzyme of creatine kinase. PMID- 4035798 TI - [Adenine nucleotide and creatine phosphate levels in rat skeletal muscles and myocardium in myorelaxation]. AB - The content of adenylic system components and creatine phosphate was determined in skeletal muscles and myocardium after intraperitoneal injection and short-term action of myorelaxin and arduan. The injected myorelaxin causes no significant changes in macroergic phosphates in skeletal muscles, whereas arduan lowers the ATP amount by 39%. The both myorelaxants have the same effect on the adenylic system components of the myocardium: they lower significantly the level of ATP and enhance that of ADP and AMP. Different variational tendences of variation in the content of creatine phosphate in skeletal muscles (a certain rise) and in the myocardium (a decrease more than by 30%) are observed. PMID- 4035799 TI - [Effect of lactate on the effectiveness of glucose and succinate oxidation by myocardium homogenates]. AB - Lactate (20 mM) was studied for its effect on the intensity of [1-6-14C] glucose and [1,4-14C] succinate oxidation by the rat myocardial homogenates. It is established that lactate induces specific suppression of aerobic glucose oxidation. A moderate reduction of the succinate and lactate oxidation in their combined incubation is of a non-specific character. PMID- 4035800 TI - [Effect of different doses of ethanol on the release of enzymes and lipids from the perfused rat liver]. AB - The perfusion in situ of the rat liver reveals appearance of enzymes of different subcellular localization, potassium ions and lipid components in the perfusate. Ethanol introduction at different doses induces the most expressed changes in the activity of catalase, lactate dehydrogenase, arginase and alanine aminotransferase and in the potassium removal from hepatocytes. A degree of the evoked changes depends on the dose. PMID- 4035801 TI - [Changes in the phospholipid composition of rat liver chromatin during treatment with hydrocortisone]. AB - When isolating protein components of chromatin from the rat liver phospholipids are found in the fraction of nonhistone proteins but not in that of histone. Administration of hydrocortisone to animals evokes a reliable increase of the phospholipids of hydrocortisone to animals evokes a reliable increase of the phospholipids amount in the preparations of chromatin and labile-bound nonhistone proteins. In this case the fraction of phosphatidylcholine lowers considerably with a simultaneous increase of sphingomyelin and phosphatidylethanolamine. It is supposed that phospholipid metabolism in chromatin is controlled by hormones, which may be significant for mechanisms of the genetic apparatus activation by steroid hormones. PMID- 4035802 TI - [Acid-base equilibrium of blood in chicken with gout]. AB - It is shown that visceral gout in chicken is accompanied by acute metabolic acidosis. The mentioned change in the acid-base equilibrium is supposed to aggravate the course of the disease. PMID- 4035803 TI - The effect of single or repeated applications of "therapeutic" ultrasound on plasma extravasation during silver nitrate induced inflammation of the rat hindpaw ankle joint in vivo. AB - The effect of "therapeutic" ultrasound upon plasma extravasation during the inflammatory process induced in the rat hindpaw ankle by intra-articular injection of silver nitrate was investigated in two series of experiments. Both series utilised three ultrasonic frequencies, 0.75, 1.5, and 3.0 MHz, and two pulse ratios, mark:space 1:4 and 1:1. Series 1 examined the effect of two durations of ultrasound, 1 or 2 min, administered once only, and series 2 examined the effect of single or repeated insonations of 1 min duration. It was found that ultrasound treatment increased plasma extravasation compared to controls during the first 24 hr, but later reduced it significantly compared to controls. This secondary effect of reduction in plasma extravasation was delayed in animals given three insonations, this number of insonations being found to prolong the plasma extravasation phase. PMID- 4035804 TI - Microstreaming shear as a mechanism of cell death in Elodea leaves exposed to ultrasound. AB - The hypothesis that ultrasonically induced membrane damage and cell death in Elodea leaves is caused by shear stress associated with microstreaming flow generated in the vicinity of oscillating gas-filled channels between the cells is investigated. Cell death thresholds as a function of frequency seem to follow a condition of constant shear stress, with minimum thresholds near the resonance frequency of a gas-filled channel. Theoretical estimates of the shear stress generated within the cells at the ultrasonic intensity of the cell death threshold are in order of magnitude agreement with measurements of the shear stress required for lysis of blood cells. Furthermore, the dependence of the cell death thresholds on exposure duration seems to correspond roughly with the dependence of critical shear stress for blood cells as a function of the duration of the stress. Membrane damage induced by microstreaming shear stress therefore appears to be a plausible mechanism of cell death in Elodea, and a valuable unifying concept for consideration of bioeffects of ultrasonic cavitation. PMID- 4035805 TI - Effect of gaseous inclusions on the frequency dependence of ultrasonic attenuation in liver. AB - The greatest variation in published data of the attenuation of ultrasound in mammalian liver in vitro occurs at the lower end of the 0.5 to 7 MHz frequency range and gives rise to some departure from a linear or simple power law dependence of attenuation on frequency. These effects do not appear to be highly dependent on the method of measurement. It is suggested that they are due to a varying presence of small gas bubbles distributed throughout the tissue--a suggestion based on calculated estimates of the attenuation due to microscopic bubbles and on the measured frequency dependence of attenuation in water loaded sponges containing varying amounts and distribution of gas. We now believe that preferred methods of tissue specimen preparation, for in vitro measurement of ultrasonic attenuation or scattering, should involve either pressurization as described elsewhere (Frizzell et al., 1979) or storage under refrigeration. PMID- 4035806 TI - The propagation of Gaussian modulated pulses in dissipative and/or dispersive media such as tissue. AB - The interrogating pulse used in most conventional medical ultrasonic imaging systems can be approximated as a band-limited Gaussian modulated pulse. In this paper we analyze the propagation of such a pulse in an attenuating media such as tissue. We show that an initially Gaussian pulse retains its Gaussian shape during propagation provided that the medium has attenuation with a power-law dependence on frequency of between zero and two. That is, if the attenuation factor is e- alpha x, where alpha is the attenuation coefficient and x is the distance over which the pulse has traveled, then the pulse will remain Gaussian provided alpha = afp, where a is a constant, f is the frequency, and 0 less than p less than or equal to 2. This condition is certainly valid for soft tissue (p approximately 1) as well as for all other attenuating materials with which we are familiar. Although a Gaussian pulse retains its Gaussian shape in an attenuating media, it does suffer a shift in its mean frequency as well as a broadening in its shape. Here we also obtain analytical expressions relating the mean frequency shift and the pulse broadening to the attenuating properties of the medium. In contrast to other studies recently published in the literature, we consider propagation in a medium which has velocity dispersion as well as frequency dependent loss. PMID- 4035807 TI - Determination of the nonlinearity parameter B/A of biological media. AB - The nonlinearity parameter B/A has been determined for various biological solutions and soft tissues using the thermodynamic and finite amplitude methods. Agreement between the two methods is better than 10% for the tissues and 1% for the solutions. Fat has a B/A value around 11, the highest among soft tissues studied. Other soft tissues including liver, muscle, brain, and heart muscle have B/A values close to 7. Based on the observed linear relation between the B/A value and solute concentration in protein solutions, and also the lack of dependence of the B/A value on solute molecular weight in dextran solutions, it is postulated that the nonlinearity in these solutions is due to solute-solvent interactions. The general trend of increasing B/A value with specimen structural hierarchy suggests that the nonlinearity of biological materials is related to this feature. These observations suggest the use of the nonlinearity parameter B/A in tissue characterization, particularly since structural alteration often attends the pathological state. PMID- 4035808 TI - [Modified Schanz screws for the external fixator]. AB - In order to make a comparison with conventional implants, our recently developed 5/8 mm screws of Schanz were put in the lateral clamp of an external fixation unit applied to the femur. By using the modified 5/8 mm screws of Schanz, an increased stability and a reduced number of implants can be achieved. The results are not only applicable for the external fixation of the femur investigated by us, but also for unilateral fixation of the tibia. PMID- 4035809 TI - Report on research in strength, elasticity and impact resistance of the cervical vertebrae. AB - The essential part of the research lay in ascertaining the sort of forces damaging in an injury of the cervical vertebral column and the circumstances under which this can also lead to spinal cord injury. Further study was devoted to the assessment of the force with which a certain part of the cervical vertebral column resists the injuring forces and in what manner it contributes to the final state of injury. The results of this research made it possible to lay down the principles of prevention from as well as treatment of the cervical vertebral column and spinal cord injury. PMID- 4035810 TI - [Fractures of the metacarpal bones II to V--conservative and surgical treatment]. AB - Fractures of the metacarpals II-V can normally be handled conservatively. After reposition under local anaesthetic plaster of Paris is applied for a duration of 3 to 4 weeks. Open fractures usually with accompanying injuries, should be stabilized operatively. The functional results of conservative treatment are very good. Slight sidewards deviation of up to 1/3 of the width of the shaft and shortening of up to 6 mm don't interfere with good hand function. Palmar deviation of the distal fragment of up to 35 degrees following subcapitular fractures does not reduce hand function. PMID- 4035811 TI - [Late results following the surgical treatment of proximal humerus fractures in adults]. AB - In this paper late results of 65 proximal humeral fractures, operated upon between 1970 and 1980 are reported. Fractures were classified according to Neer in two-part-(28), three-part-(15), four-part-fractures (21) and fractures of the articular surface (1). In 34 cases internal fixation was performed by a T-plate. In 15 cases either open reduction without internal fixation or open reduction and minimal internal fixation was done using screws and K-wires. Primary prosthetic replacement of the head was done in 8 patients with four-part-fractures. The follow-up period ranged from 2.5 years up to 13 years with an average of 7 years. The functional results were excellent in 25 patients, good in 14, fair in 10 and poor in 16 patients. Better results were obtained in young patients, isolated shoulder injuries and patients with two- or three-part-fractures. On the contrary the results in aged and polytraumatized patients or patients with four-part fractures and fracture dislocations were less favourable. Avascular necrosis of the humeral head was encountered in 4 cases of four-part-fractures and fracture dislocations, 3 of them fixed by T-plate and 1 by minimal internal fixation. No case of avascular necrosis of the humeral head was encountered in two- or three part-fractures, fixed by T-plate. We can conclude, that cases, having a high risk for developing avascular necrosis of the humeral head, i.e. four-part-fractures and fracture dislocations, are better treated with minimal internal fixation avoiding the use of T-plate, for it was found to increase the already present damage. PMID- 4035812 TI - [Fractures in the elbow joint area in childhood and adolescence]. AB - 73 cases of elbow joint fractures were treated in our Dep. of Paediatric surgery over a period of 10 years. Most of the fractures in the region of the distal humerus are localized at the ulnar epicondyle and the radial condyle. At the proximal forearm the radial head and the radial collum fractures are dominant in respect to olecranon fractures. Only two cases involved a comminuted fracture of the distal humerus. Due to the fact that only a small number of cases involving a fracture of the radial epicondyle after a luxation of the elbow were registered, it is possible that we paid no attention to this kind of fractures. An early functional therapy in the case of segmental fracture of the radial head must be emphasized among the 11 cases with a conservative treatment. Another 3 cases with a radial head fracture, type Judet III, should be mentioned, because they were treated without reposition but were spontaneously redressed. The operation procedure and the late results by 62 patients are discussed with the results of other examiners. As expected the comminuted fractures of the distal humerus and the radial head had a bad prognosis. Functional relevant dislocations were rare. Only in one case after a conservative treatment of a lateral condyle fracture a development of a valgus position with a pseudarthrosis after a secondary dislocation was observed. In more than 90% of our cases we could achieve a complete anatomical reposition with good to very good functional results. PMID- 4035813 TI - [The value of the Duopleet prosthesis for the treatment of femur neck fractures]. AB - The clinical course of 68 patients with femoral neck fractures is reported. Fracture management was chosen regarding age and accompanying health defects. Fracture management, operation time, complications, mobilization results and hospitalization time is described, compared to other authors and discussed. The results favor the implantation of a Duopleet prosthesis as the salvage operation of choice for femoral neck fractures of old patients beyond 75. Other methods are considered to remain valuable with differentiated indication. PMID- 4035814 TI - [Secondary interventions following injuries of the upper ankle joint]. AB - Fractures of the upper ankle joint require anatomic functional reposition and stabilisation in operative or conservative way. Prearthrotic alterations following inadequate treatment want secondary reconstructive measures in the early stages, whereas in manifest posttraumatic arthrosis you have to take arthrodesis as alternative treatment into consideration, which shows good results using nowadays reliable technics. PMID- 4035815 TI - [Complications in drug prevention of thromboembolism]. AB - The possibility of complications during the thrombembolic prophylaxis with heparin-dihydroergotamine requests the observance of the application and the contraindications. The information of the patients and the continuous clinical control are absolutely necessary. The thrombembolic prophylaxis with less risk is given in a sufficient medication with Heparin in connection with early active exercising and correct positioning of the patient. PMID- 4035816 TI - EEG and evoked potential changes during gas- and liquid-breathing dives to 1000 msw. AB - To test the hypothesis that compression in helium gas and compression without gas (hydrostatic compression) both produce the same neurological symptoms of high pressure nervous syndrome (HPNS), groups of 4 to 5 dogs were exposed to one of the following: (a) a 2-h surface control breathing He-O2 gas; (b) compression to 700-1000 msw breathing He-O2 gas; (c) a 2-h liquid-breathing control [ventilation with warmed (38 degrees C), oxygenated fluorocarbon liquid, FC-80]; and (d) "near hydrostatic" compression to 700-1000 msw while being ventilated with liquid from a sealed reservoir. Power spectra obtained from scalp-recorded EEG signals revealed a significant compression-related shift of power from the normally dominant 5-8 Hz band to the 8-11 Hz band. This effect was greatest at 600 msw and occurred equally in both dive groups. At very high pressures (greater than 900 msw) power in this 6-10 Hz range became reduced whereas 16-22 Hz activity increased as the EEG flattened. Somatosensory evoked potentials (SEPs) were elicited by subdermal electrical stimulation in the foreleg (n = 120). The latency of P1 (approximately 31 ms) did not change in any group; transmission time to cortex was unaltered by time or pressure. However, the "late-wave" P4 (approximately 250 ms) was slowed by 32-35 ms at 1000 msw in both groups (P less than 0.003 in He-O2). Since these main symptoms were provoked equally in both He O2 and FC-80 dive groups, helium pressure did not play a significant role in the etiology of HPNS in this animal model. It is concluded that the HPNS is primarily a result of excessive pressure per se or rate of change of pressure per se. PMID- 4035817 TI - Air and nitrox saturation decompression: a report of 4 schedules and 77 subjects. AB - Seventy-seven subjects were decompressed from air or nitrogen-oxygen (nitrox) saturation exposures at 18.3 to 40.2 meters sea water (msw) [60 to 132 feet sea water (fsw)] using four different decompression schedules. A h schedule for decompression from an air saturation-excursion profile at 18.3 msw (60 fsw) resulted in pain-only decompression sickness (DCS) symptoms in 2 of 23 subjects. A 32 and 35 h schedule from a different air saturation profile at 19.8 and 22.9 msw (65 and 75 fsw), respectively, resulted in DCS symptoms in 1 of 24 subjects. A third and fourth schedule for air or nitrox saturation at 40.2 msw (132 fsw) resulted in DCS symptoms in 3 of 12 and 1 of 18, respectively. No serious (type II) symptoms were observed as a result of any of the decompressions. All DCS cases consisted of knee pain occurring either in the last 3 msw of the decompression or shortly after surfacing. Doppler ultrasound monitoring revealed venous gas emboli (VGE) in several subjects, but generally only shallow to 6.1 msw (20 fsw). Results demonstrate an overall DCS incidence of 9%, and all cases were pain-only and localized to the knee. The third schedule (U.S. Navy heliox saturation decompression schedule) seems to produce a higher incidence of DCS than the other schedules when used in air or nitrox exposures. Differentiation between the schedules designed for nitrox was impossible due to the limited number of subjects in each and the variable nature of the exposures. PMID- 4035818 TI - Tissue distribution of penicillin during constant rate infusion in rats at 71 ATA. AB - Benzyl[14C]penicillin was infused at a constant rate of 100 mg X kg-1 X h-1 for 90 min in rats at 1 ATA air for the control group (n = 10) and at 71 ATA He-O2 for the pressure group (n = 11). The radioactivity was measured in the arterial blood, brain, liver, kidney, muscle, and fat. The mean brain penicillin concentration after 90 min infusion was approximately 20% increased at 71 ATA (P less than 0.05), but the brain: blood concentration ratio was not significantly affected. The mean blood, liver, and muscle penicillin content was slightly higher and the mean kidney content was slightly lower at pressure, but no statistically significant changes were observed. PMID- 4035819 TI - Evaluation of oral problems in divers performing electrical welding and cutting under water. AB - A study of 118 professional commercial divers, using an inquiry form, revealed that 55% of the divers complained about a metallic taste in the mouth when working with electrical equipment under water. A nationwide clinical examination of 40 divers was performed to see if the metallic taste during work reflected any alteration in the oral cavity. The clinical appearance of the dental amalgam restorations differed significantly between divers who had been working with electrical equipment and divers who had not. A number of other dental indexes were assessed and showed no differences between the two groups. These included salivary secretion rate, buffering capacity, secondary caries, plaque index, bleeding index, and cultures of S. mutans and Lactobacillus. Relatively high levels of the two organisms were noted, indicating that the group of divers examined should be considered as a caries risk groups. PMID- 4035820 TI - Damage to the middle ear and the inner ear in underwater divers. AB - Postmortem human tissue from recently deceased divers was processed histologically to assess any inner and middle ear damage that could have resulted from the effects of pressure during diving. The following new findings are particularly noteworthy. In one diver, ascent while breath holding resulted in the rupture of the ear drum and blood in the middle ear, in addition to pulmonary barotrauma. In a second diver, following inner ear decompression sickness, new bone growth, similar to that described earlier in experimental studies with the squirrel monkey, was observed in the arms of one of the semicircular canals. These observations are further confirmation that otologic disorders can be a serious threat to divers. PMID- 4035821 TI - Thermal environmental monitoring of divers using a twelve channel multiplexing instrument. AB - A 12-channel temperature monitoring instrument designed for use by divers while immersed or within pressure chambers is described. Data are multiplexed at the diver and transmitted to the surface, bell, submarine, or chamber exterior through a two-core electrical cable. In the case of the immersed diver the cable may be incorporated into the diver's umbilical cable. Details of the method and special construction techniques used in the design of the diver-borne multiplexer are given. At the dive control station the 12 individual temperatures may be displayed in either digital or analogue format. The temperature data may also be stored on one track of a battery-powered magnetic tape recorder for subsequent off-line analysis. PMID- 4035822 TI - [Clinical observations on 76 children exposed to urea-formaldehyde insulation foam]. PMID- 4035823 TI - [The influence of the lunar cycle on delivery]. PMID- 4035824 TI - [The full moon, cosmic panacea or prehistoric prostaglandin]. PMID- 4035825 TI - [Detection and scintigraphic evaluation of varicoceles using 99mTc-red blood cells: preliminary results]. PMID- 4035826 TI - [Rapid detection of septicemia using a laser nephelometer]. PMID- 4035827 TI - [Deinstitutionalization. 1]. PMID- 4035828 TI - [Causes and prevention of complications in transurethral interventions. Interventions in the urethra]. AB - The male urethra is extremely vulnerable because of the peculiar morphology. Many urethral lesions and their sequelae are due to the disproportion between the diameter of the urethra and the applied instrument. In order to adjust both calibers it is advisable to use an internal urethrotomy in stead of bougies. Complications which may be caused by catheterisation, and by the treatment of meatal stenosis or urethral strictures and how to avoid them are discussed. In spite of improvements in transurethral equipment and careful transurethral operative technique, perioperative prophylaxis with potent antibiotics, is recommended in order to prevent late complications due to infections. PMID- 4035829 TI - [Complication of ureterorenoscopy]. AB - We describe failures and complications of ureterorenoscopy based on our own experience and the literature. There is usually no consequence when perforating the ureter--which happens in 10 per cent of the cases--if a splint or a percutaneous nephrostomy is applied. Ureteral rupture makes an open intervention necessary, but happens rarely. Since complications of ureterorenoscopy are rare and the rate of success very high, open operations on the ureter should become less frequent. PMID- 4035830 TI - [Controversial aspects of the genesis of megaureter]. AB - The cause of congenital ureter dilatation as well as its nomenclature are controversial. The question arises as to whether there is a common denominator for this multiform syndrome. There are abundant possibilities of disturbance during the development of the ureter. The muscle coat of the developing fetal ureter reacts with an alteration of the wall structure. In view of the multiplicity of etiological factors which can affect the development of the ureter, a disturbance of intrauterine urinary drainage which is transient or permanent probably has a functional or mechanical basis. At any events, a subvesical obstruction, which may also be the cause, must be excluded. PMID- 4035831 TI - [Spermatogenesis in patients with traumatic transverse paralysis]. AB - Testicular biopsies from 22 paraplegic men were studied by light and electron microscopy. The investigations of semithin sections by a special standardized method revealed that normal spermatogenesis occurred in only one patient, whereas in 21 patients severe disturbance of spermatogenesis was found. The germinal epithelium displayed a decrease of spermatogenic cells, an increase of degenerating cells, especially of spermatids, and a release of large groups of premature germ cells. Cross sectioned tubules often showed no patent lumina. As revealed by electron microscopical investigations the spermatids show malformations in most cases of the head and acrosome, rarely of the tail. Decreased spermatogenic activity occurred in various degrees in each of the 21 men. There is no evidence that any specific form of spermatogenic disturbance exists typical of spinal cord injury. No obvious relationship was found between the degree of spermatogenic disturbance and duration or level of the spinal cord lesion or incidence of urinary tract infection. PMID- 4035832 TI - [Persistent microhematuria: localization of the source of bleeding by the evaluation of erythrocyte morphology]. AB - Evaluation of erythrocyte morphology enables differentiation between renal parenchymatous and postrenal microhematuria. In case of renal erythrocyturia, further examination is carried out with a nephrologist following abridged urologic examination. If the erythrocytes in the urinary sediment are established as being unchanged (postrenal cause of bleeding), a complete urological check is carried out. Today, renal-parenchymatous erythrocyturia can be established with great certainty without a kidney biopsy. PMID- 4035833 TI - [Adrenal myelolipoma. Case report]. AB - Adrenal myelolipomas (a. M.) are rarely occurring, benign, unilateral, hormonally inactive, mostly asymptomatic tumors of the adrenal cortex, consisting of fat cells and myeloid tissue. The pathogenesis is not clear. There is no connection with hematologic diseases, but a strikingly frequent coincidence with chronic systemic diseases and obesity. Myelolipomas of the presacral as well as in the mediastinal space are very rare. Case report of an adrenal myelolipoma removed by lumbotomy. PMID- 4035834 TI - [Fusion of an ectopic spleen with the left kidney. Preoperative diagnosis: adenocarcinoma of the kidney]. AB - We report on the case of a left retroperitoneal accessory spleen with splenorenal fusion. Computed tomography demonstrated a solid mass arising from the left kidney and angiography revealed no abnormality, leading to the preoperative diagnosis of a poorly vascularized carcinoma of the kidney. PMID- 4035835 TI - Urachal carcinoma. AB - The clinical and morphologic features in 14 cases of urachal adenocarcinoma are reviewed. The disease occurred more frequently in men than in women. Seven patients (50%) remain alive and currently free of disease at periods ranging from fifteen months to ten years (median: 6 years). Neither the histologic appearance nor the differentiation of the tumor appeared to affect prognosis. It is concluded that the criteria previously recommended to establish the diagnosis of this rare malignancy were too restrictive. PMID- 4035836 TI - Priapism: etiology, treatment, and results in series of 35 presentations. AB - Of 35 cases of priapism a successful outcome with detumescence of the erection and preservation of potency was achieved in only 6 instances. Patients with sickle cell disease enjoyed a more optimistic outcome, and early presentation appeared to be the key factor. The different therapeutic approaches did not have great impact on the outcome, and we advise an initial conservative approach progressing to glans-cavernosa fistula creation and subsequently to cavernosum spongiosum shunting for patients failing to respond. PMID- 4035837 TI - Priapism: review of 34 cases. AB - One hundred ninety-seven cases of priapism have been recorded in the medical files of Charity Hospital Louisiana in New Orleans from 1938-1982. One hundred seventy-two adults and 25 children were registered in this series. Ninety-three per cent of the patients with priapism were black, and 86 patients of this group underwent 93 surgical procedures. The cases of 34 patients treated between July 1, 1981, and December 31, 1982, were thoroughly reviewed. Sixteen patients had a previous history of priapism. Average delay between onset of symptoms and presentation to the hospital for treatment was thirty hours. Sickle cell screens were obtained in 28 patients and were positive in 17. Twenty-nine patients were initially treated conservatively, with 17 priapisms eventually resolving, but the remaining 12 patients required surgical intervention. Overall, 50 per cent of the 34 patients had surgery. All of the surgical cases resolved satisfactorily with the Winter procedure. Complications with this procedure were uncommon, but postoperative bandaging was the chief cause of morbidity. Follow-up for at least six months revealed comparable sexual potency (80-83%) in either conservatively or surgically managed patients. PMID- 4035838 TI - Testosterone receptors in corpora cavernosa of penis. AB - Despite existing information that most impotent patients have normal serum testosterone, testosterone is still used frequently in the treatment of impotence. In 11 patients who underwent penile implantation, we measured the presence of testosterone receptors in the corpora cavernosa. An average value of 1.82 fmol/mg of protein cytosol was found in this group of patients. This value is too low to obtain any significant improvement in erectile function following testosterone application. Testosterone hypogonadism will likely remain the only indication in which testosterone application might improve organically triggered impotence. PMID- 4035839 TI - Urolithiasis in acromegaly. AB - Hypercalcemia, hypercalciuria, and hyperphosphatemia are common findings in acromegaly, yet there are only a few reports on the occurrence of urinary stones in these patients. We reviewed the files of 64 patients with acromegaly. A total of 8 patients had evidence of renal calculi: 4 patients underwent nephrolithotomy, 3 had stones which were seen on intravenous pyelography, and 1 patient voided a stone. Moreover, 2 other patients suffered from recurrent typical episodes of renal colic. In view of the high incidence of urolithiasis in our series we believe that more attention should be paid to detection of urinary stones in acromegalics to avoid further complications and suffering. PMID- 4035840 TI - Results of radical cystectomy for primary bladder cancer. Retrospective study of more than 200 cases. AB - During a seven-year period 202 patients with primary bladder cancer had radical cystectomy with bilateral pelvic lymphadenectomy and urinary diversion. Lymph node metastases were found in 28.7 per cent. No significant differences in overall survival owing to age were apparent. Only extension and grade of histopathologic differentiation of the tumor proved to be an important prognostic factor. The five-year survival rates for pT1, pT2, pT3, and pT4 tumors were 76, 56, 19, and 0 per cent, respectively. In patients with deep invasive (T3 and T4) tumors no significant differences of survival rate depending on N and M categories were found. Nevertheless in pT3 tumors the probability of remaining alive was significantly decreased in those patients with histologic grade 3 compared with grade 2 tumors (P less than 0.01). The prognosis for patients submitted to radical cystectomy for bladder cancer has been classified as good: tumors confined to superficial muscle (pT1 and pT2); intermediate: tumors mildly differentiated infiltrating the deep muscle (pT3/G2); fairly poor: tumors undifferentiated infiltrating deep muscle (pT3/G3); and poor: adjacent invasive bladder tumors (pT4). PMID- 4035841 TI - Type of blunt renal injury rather than associated extravasation should determine treatment. AB - The significance of extravasation of dye during excretion urography in blunt renal injuries has been controversial, with some believing that extravasation, even if copious, is largely innocuous and characterized by spontaneous resolution, and others believing extravasation is an indication for surgical correction of the underlying blunt renal injury. Thirty-two patients with extravasation diagnosed on excretion urography after blunt external trauma were evaluated. Immediate surgical management of the renal injury was performed in 18 patients who had a contusion in 1, laceration in 13, rupture in 3, and pedicle injury in 1, and averaged 2.0 associated injuries per patient. Conservative management of the renal injury was performed in 14 patients who averaged 1.1 associated injuries per patient. Ten of the 14 patients had a large renal laceration splitting the kidney or disrupting a pole with extravasation and none settled to normal. The data showed that extravasation with a small laceration resolved spontaneously while extravasation with a major disruption of the kidney did not settle to normal. PMID- 4035842 TI - Epispadias: contending with continence. AB - Forty-seven patients with epispadias not associated with bladder exstrophy were treated at our institution over the last half decade. There were 8 female and 39 male patients, 37 of whom had retrosymphyseal epispadias. Of the 20 male patients with subsymphyseal epispadias and incontinence 13 had a fair to excellent result. Of the 7 females with retrosymphyseal epispadias and incontinence, all but 1 came to urinary diversion. An analysis of our data suggests that premature operative intervention precludes obtaining maximal functional and cosmetic results. In addition, the discrepancy in our overall success rate utilizing a one-stage technique versus a staged procedure favored by others may support the latter. PMID- 4035843 TI - The child with solitary hydronephrotic kidney. AB - The child with solitary hydronephrotic kidney has a prognosis different from that of the child with hydronephrosis and a normal contralateral kidney. We have reviewed a decade of experience with 31 children with solitary hydronephrotic kidney and have identified characteristics that point to either a favorable or unfavorable prognosis in these children. PMID- 4035844 TI - Nonpsychotic genital self-mutilation. AB - The case of a sixty-four-year-old man who progressively created a penoscrotal hypospadias on himself is presented. Although genital self-mutilation is normally considered symptomatic of deep psychotic disturbance, the details and evaluation of this case would classify it as nonpsychotic, though unusual behavior. PMID- 4035845 TI - Seminoma and sarcoidosis: an unusual association. AB - A case is reported of the concurrent presentation of anaplastic seminoma and mediastinal sarcoidosis. This is an exceedingly rare synchronous appearance of both entities and requires meticulous staging prior to initiating definitive therapy. PMID- 4035846 TI - Aldosterone-producing gigantic adrenocortical adenoma with calcifications and cysts. PMID- 4035847 TI - Epididymal metastasis from prostatic carcinoma. AB - A case of epididymal metastasis from carcinoma of the prostate with an unusual presentation is reported. A review of the literature disclosed only 10 reported cases of this rare finding. A mechanism for the method of metastasis in this patient is proposed. PMID- 4035848 TI - How to deflate refractory balloon of a bladder catheter. PMID- 4035849 TI - Metastatic extraosseous myxoid chondrosarcoma of spermatic cord. AB - A patient with extraosseous myxoid chondrosarcoma arising from the spermatic cord had nine local recurrences and ultimately two metastatic lung lesions over an eleven-year-period from the time of diagnosis. PMID- 4035850 TI - Primary intrascrotal nontesticular schwannoma. AB - A supratesticular intrascrotal mass clinically mimicking a spermatocele was found to be a scrotal neoplasm histologically identified as a schwannoma. We herein present the first case of intrascrotal schwannoma to our knowledge. PMID- 4035851 TI - Fibrosarcoma of epididymis. AB - We present a case of fibrosarcoma of the epididymis occurring in a sixty-year-old man. While review of the literature has failed to determine an exact number of such cases reported, we believe the number is small. We discuss the treatment options and prognosis for these patients. PMID- 4035852 TI - Case profile: massive bladder retention in a female. PMID- 4035853 TI - Emphysematous renal and perirenal infection in nondiabetic patient. AB - Emphysematous renal infection is a severe, rare complication of urinary tract infection associated with gas production, which frequently causes renal destruction and has a high mortality rate. It is termed emphysematous pyelitis when gas is confined to the collecting system, or emphysematous pyelonephritis if it also involves the parenchyma with or without the perirenal space. Only 7 cases of perirenal emphysema have been described previously; all were in diabetics. Here we present a rare case of gas-producing renal infection in the collecting system and perirenal tissues, in a nondiabetic patient, and discuss the management of the various types of emphysematous renal infections. PMID- 4035854 TI - Simultaneous registration of sleep-stages and bladder activity in enuresis. AB - A combined monitoring of sleep stages and bladder activity for the evaluation of enuresis is on trial. Polygraphic recordings in 7 patients, comprising the preliminary material, have shown single-event bladder contractions without forewarning or changes in sleep stages. A volume dependency of the enuresis episodes seems so far to be a major mechanism. PMID- 4035855 TI - Retrograde pyelography using resectoscope. PMID- 4035856 TI - Stress cause of prostatitis. PMID- 4035857 TI - Vacuum cleaner injury to penis. PMID- 4035858 TI - [Episcleral venous pressure in primary glaucoma, ocular hypertension and in patients with hypertension]. PMID- 4035859 TI - [Late results and outflow routes following the operation of iridocycloretraction]. PMID- 4035860 TI - [Effect of the nature of matching margins of cataract incisions on the formation of postoperative astigmatism]. PMID- 4035861 TI - [Microsurgery for extracapsular cataract extraction using an aspiration irrigation system]. PMID- 4035862 TI - [Device for aspiration and irrigation of the crystalline lens mass in extracapsular cataract extraction]. PMID- 4035863 TI - [State of the corneal endothelium in patients with cataracts of different etiology]. PMID- 4035864 TI - [Pathogenetic approach to the treatment of posttraumatic subatrophy of the eye]. PMID- 4035865 TI - [Theory of the pathogenetic relation of hydrophthalmia with open-angle glaucoma]. PMID- 4035866 TI - [Possibilities of using the CO2-laser in plastic surgery of the eyelids]. PMID- 4035867 TI - [Treatment of hypoxic conditions of the cornea]. PMID- 4035868 TI - [Selenium content and glutathione peroxidase activity in human eye tissues in diabetes]. PMID- 4035870 TI - [Genesis and evolution of amiodarone keratopathy]. PMID- 4035869 TI - [Reaction of the conjunctival and retinal vessels to the administration of vasodilators to patients with vascular disorders of the fundus oculi]. PMID- 4035871 TI - [Nonsurgical method of treating chalazion in pediatric ophthalmological practice]. PMID- 4035872 TI - [Experimental validation of the use of idoxuridine magnetophoresis in herpesvirus eye infections]. PMID- 4035873 TI - [Clinical characteristics of cataracts in children with hereditary metabolic disorders]. PMID- 4035874 TI - [Conjunctival smears in preparation for ophthalmologic operations]. PMID- 4035875 TI - [Device for demagnetizing microsurgical instruments]. PMID- 4035876 TI - [Effect of methodological aids for self instruction on the initial level of knowledge of students]. PMID- 4035877 TI - [Lens disorders in workers in electrolytic shops]. PMID- 4035878 TI - [Case of treatment of keratitis caused by Pseudomonas pyocyanea and complicated by candidiasis]. PMID- 4035879 TI - [Screening method for early detection of glaucoma]. PMID- 4035880 TI - [Case of penetrating wound to the eye from a fishhook]. PMID- 4035881 TI - [Comparative studies of the efficacy of laser therapy of common and pseudoexfoliative primary open-angle glaucoma]. PMID- 4035882 TI - [World physicians for prevention of nuclear war]. PMID- 4035883 TI - [Use of brain stem auditory evoked potentials in the diagnosis of retrocochlear pathology]. PMID- 4035884 TI - [State of the bulbar conjunctival vessels in patients with acute neurosensory hearing disorders]. PMID- 4035885 TI - [Subjective and objective tinnitus in brain diseases and their differentiation from peripheral tinnitus]. PMID- 4035886 TI - [Social rehabilitation of patients in the late period after surgery for an otogenic brain abscess]. PMID- 4035887 TI - [Topographic-anatomic interrelations of structures of the brain and the trepanation auricular cavity]. PMID- 4035888 TI - [Visual motor coordination test in the differential diagnosis of Meniere's disease]. PMID- 4035889 TI - [Role of biochemical, coagulative and rheologic changes in the blood in the pathogenesis of acute neurosensory hearing disorders]. PMID- 4035890 TI - [State of the mucociliary apparatus in chronic dust-induced bronchitis]. PMID- 4035891 TI - [Laser therapy of inflammatory diseases of the paranasal sinuses]. PMID- 4035892 TI - [Clinical characteristics of cancer of the laryngeal ventricles and efficacy of different methods of treatment]. PMID- 4035893 TI - [Surgical tactics in ENT diseases in patients with hemophilia]. PMID- 4035894 TI - [Relation of occupational diseases of the upper respiratory tract to changes in local immunity indices]. PMID- 4035896 TI - [Chronic purulent otitis media complicated by an extensive phlegmon of the neck]. PMID- 4035895 TI - [Evaluation of sensitization to staphylococcus by determining indices of neutrophil damage by new allergenic preparations]. PMID- 4035897 TI - [Rare case of otogenic sepsis]. PMID- 4035898 TI - [Traumatic cholesteatoma of the temporal region complicated by a brain abscess]. PMID- 4035899 TI - [Glioma of the nasal cavity]. PMID- 4035900 TI - [Gunshot wound of the neck complicated by mediastinitis and hemorrhage]. PMID- 4035901 TI - [Pneumosinus of the frontal sinus]. PMID- 4035903 TI - [Acute cerebrovascular disorder simulating a foreign body in the throat]. PMID- 4035902 TI - [Neurinoma of the root of the tongue]. PMID- 4035904 TI - [Course of otomycosis in the Republic of Bangladesh]. PMID- 4035905 TI - [Lymphangiomas of the omentum in children]. AB - The authors observed 40 patients with lymphangiomas, 8 cases with omentum lymphangioma included. The clinical course and treatment are described. Long-term results are good. PMID- 4035906 TI - [Causes of recurrence of congenital clubfoot in children and indications for surgical treatment]. AB - Unsatisfactory results of the conservative treatment of club foot deformity in 220 patients (346 feet) were analyzed. Data of roentgenograms in 86 patients enabled the authors to make a conclusion that an early cause of recurrent club foot is the delayed formation of nuclei of ossification of the navicular and I sphenoid bones, the later cause of the recurrent deformity is early synostosis of the epiphysis of the metatarsal bone. The importance of dispensary observation ad prophylactic measures after the treatment of congenital club foot is emphasized. PMID- 4035907 TI - [Allogeneic tendoplasty in surgery of the locomotor system]. AB - Allogenic tendotransplants were used in the treatment of different lesions and diseases of the locomotor apparatus in 410 patients. Good anatomical and functional results were obtained in 84% of the patients. Unsatisfactory results were noted in 7% of cases. The method of preservation of allogenic tendons had no influence upon the results. PMID- 4035908 TI - [Use of propolis in the treatment of local suppurative infection]. AB - Experience with the treatment of 460 patients with panaritium, abscesses, phlegmons, infectious wounds have shown that propolis is an expedient remedy (in additional to the the routine treatment). They have shown the stimulating, antiinflammatory and anti-microbial action of propolis. PMID- 4035909 TI - [Synovial cysts of the fingers and toes]. PMID- 4035910 TI - [Tactics in the surgical treatment of nodular euthyroid goiter]. AB - Based upon the experience with the treatment of 2759 patients the authors have established indications for surgery for nodular neoplasms of the thyroid since cancer can develop in the guise of or parallel with them. Such patients must be examined and operated upon under conditions of specialized hospitals. Grounds for indications for local and general anesthesia are given as well as for intrafascial resection of the thyroid as the operation of choice for nodular forms of euthyroid goiter. PMID- 4035911 TI - [Operative technic in nodular goiter and cancer of the thyroid]. AB - Based on the literature data and personal experience the author recommends the extrafascial technique of operation in cases with thyroid cancer. In nodular and polynodular goiters a subfascial operation is necessary since it prevents many complications. PMID- 4035913 TI - [A tendon conductor]. PMID- 4035912 TI - [Reinforcing a large intestine anastomosis with a flap from the gastric wall]. PMID- 4035914 TI - [Use of a metal ball in operative cholangiography]. PMID- 4035915 TI - [Errors in the diagnosis and treatment of patients with injuries of the major blood vessels]. PMID- 4035916 TI - [Catheterization of the subclavian vein complicated by thrombosis and thrombophlebitis]. PMID- 4035917 TI - [Rare complication after removal of the catheter from the subclavian vein]. PMID- 4035918 TI - [Methods of preoperative and operative prevention of thromboembolic complications of intra-atrial thrombosis]. AB - Methods of preoperative and operative prophylactics of thromboembolic complications in patients with mitral stenosis complicated by intraatrial thrombosis are described. In a group of patients given anticoagulants during a month as preoperative preparation there was a six times decreased amount of thromboembolic complications in the nearest postoperative period. The anticoagulant treatment is thought to be effective when applied continuously (no less than 3-4 weeks); no complications due to anticoagulant therapy were noted. PMID- 4035919 TI - [Thoracoscopy in nonspecific spontaneous and iatrogenic pneumothorax]. AB - Thoracoscopy was used in 92 patients. The etiology of pneumothorax was established in 76 patients. In most of them the treatment was effective. Suture of the pleura and lung defect, pleurodesis, pleurectomy, coagulation of tissues were performed under the control of thoracoscope. Thoracoscopy allowed to avoid extensive thoracotomy, to shorten the period of treatment at the hospital. PMID- 4035920 TI - [Transthoracic intrapulmonary administration of antibiotics with an injector in the treatment of acute pneumonia]. PMID- 4035921 TI - [Effectiveness of the conservative treatment of patients with cicatricial stricture of the esophagus of different durations]. AB - High efficiency and safety of bougieurage of the oesophagus with a metallic cord is shown. Conservative treatment of the postburn narrowing of the oesophagus associated with preventive bougieurage proved to be highly effective in patients admitted to the hospital with an early stage of the disease. There were no lethal outcomes. The continuous purposeful complex treatment of patients with cicatrical narrowing of the oesophagus is recommended during 1,5-2 years after burn. PMID- 4035922 TI - [Motor-emptying function of the stomach at different periods after truncal vagotomy with antrumectomy in complicated duodenal ulcer]. AB - The paper is devoted to analysis of results of the investigation of the motor evacuatory function of the stomach at different terms after truncal vagotomy with antrumectomy in patients with complicated duodenal ulcers. Postvagotomy gastrostasis was shown to be twice more frequent after antral resection with anastomosis by Billroth-I than by billroth-II. Truncal vagotomy with antrumectomy is not recommended for patients with duodenal ulcers complicated by decompensated stenosis. Gastric resection is thought to be the operation of choice in such cases. PMID- 4035923 TI - [Various aspects of preoperative diagnosis and treatment of patients with mechanical jaundice and hepatic insufficiency]. AB - Treatment of 265 patients with mechanical jaundice is analyzed. From the first day all the patients were given the intensive infusion treatment in order to reduce intoxication, hepatic insufficiency and to prepare for operation. In 88 patients the complex of diagnostic and curative measures included sorption methods (hemosorption and lymphosorption). It allowed to make the exact diagnosis within the first 2-3 days, to determine the level of biliary block, intoxication degree and severity of hepatic insufficiency. The patients were prepared for operation within 7 days which gave better results and made the treatment 10-12 days shorter. PMID- 4035924 TI - [Method of surgical treatment of patients with hyperlipoproteinemia]. AB - In 200 operations of partial shunts of the small intestine in patients with hyperlipoproteinemia the authors have used their modification of the technique of partial ileoshunts in patients with normal weight and jejuno-ileoshunts in patients with morbid obesity. The modification has considerably reduced the amount of postoperative complications. The authors recommend using the procedure at the hospitals dealing with problems of metabolic surgery. PMID- 4035925 TI - [Subtotal colectomy in the treatment of intestinal obstruction in cancer of the left half of the colon]. AB - Eleven cases of acute obstructing carcinoma of the left colon were treated by emergency subtotal colectomy with immediate ileocolorectal anastomosis. The procedure of on-table closed antegrade preparation of the small bowel has been developed by the authors preventing the anastomosis incompetence. In all cases during postoperative treatment the long-tube decompression, enteral tube feeding and HBO were used. Two patients died. In five cases non-fatal postoperative complications have developed. Further research is recommended for more careful selection of patients for the procedure. PMID- 4035926 TI - [Surgical treatment of diffuse polyposis of the large intestine]. AB - A technique of the operation developed by the authors for patients with diffuse polyposis of the colon is described. A new method of total colectomy is proposed including removal of the rectum mucosa and the endorectal loop ileoanal anastomosis and simultaneous creation of the small intestine reservoir (operations on 2 patients) and a new method of creation of the small intestine reservoir (operations on 7 patients). Good functional results were obtained. Six eight months after operation the patients had stools 1-6 times a day. In none of 5 men operated upon impotence has developed. PMID- 4035927 TI - [Treatment of gangrene of the lower limbs in diabetes mellitus]. AB - In 54 patients with diabetic gangrenes of lower extremities the complex treatment was used aimed at changing moist gangrene into dry one, decreased intoxication, normalization of carbohydrate metabolism and improvement of tissue trophicity. In 18 patients the complex of curative measures included the antiinflammatory roentgen therapy. The efficiency of the treatment used was noted, the percentage of amputation re-reduced to 25,9%. The level of immune complexes became normal in the favorable course of the disease. PMID- 4035928 TI - [Endovascular embolization of the hepatic artery in hemobilia complicated by acute stomach ulcers]. PMID- 4035929 TI - [Cystoid pneumatosis of the intestine]. PMID- 4035930 TI - [Ectopic tissue of the pancreas in the major duodenal papilla]. PMID- 4035931 TI - [Multiple aneurysms of the splenic artery]. PMID- 4035932 TI - [Hemostatic reactions during operations on brain tumors]. PMID- 4035933 TI - [Clinical course, diagnosis and treatment of thoraco-abdominal injuries]. AB - High incidence of diagnostic errors in thoracoabdominal wounds is due to the critical state of the patients, insufficient clinical examination and underestimation of localization of the wound hole. Errors in diagnosis result in the incorrect sequence of surgical procedures, time loss during the arrest of bleeding, use of traumatic operative accesses. PMID- 4035934 TI - [Clinico-lymphographic classification of post-traumatic edema]. AB - The article generalizes the experience with diagnosis of disturbances of the lymph flow in 133 patients with edema after extremity traumas. On the basis of clinico-lymphographic examinations a classification of posttraumatic edemas is proposed facilitating the selection of the method for treatment of such patients. PMID- 4035935 TI - [Late secondary hemorrhage complicated by cardial arrest]. PMID- 4035936 TI - [Plaster bandage in fracture of the clavicle]. PMID- 4035937 TI - [Incarcerated diaphragmatic hernias in children]. AB - Results of the treatment of 19 children aged from 1,5 months to 8 years with different forms of hiatal hernias are analyzed. Specific features of the clinico roentgenological picture of the disease is described with special reference to the child's age and type of hernia. Methods of the surgical treatment are proposed. PMID- 4035938 TI - [Surgical treatment of vasorenal hypertension in children and adolescents]. AB - Problems of the surgical treatment of vasorenal hypertension in children are elucidated as well as types of reconstruction of the renal arteries, indications and contra-indications for surgery. Results of 34 operations fulfilled for fibromuscular lesions of the renal arteries in 32 patients and causes of reoperations and resection of the organs are analyzed. PMID- 4035939 TI - Pathology of an ulcerative dermatitis in Belgian Landrace sows. AB - Chronic ulcers of the skin were observed in three Belgian Landrace sows. Lesions were located on ears, limbs, and in the mammary region and were resistant to treatment that included corticosteroid therapy. Major histologic changes were located at the dermo-epidermal junction. Ulcers were deep, and the adjacent epidermis had marked hyperkeratosis, acanthosis, and intracellular edema. Dermatitis was prominent, essentially located in the superficial dermis. By electron microscopy, basal lamina appeared disrupted. Dermo-epidermal separation occurred beneath the basal lamina. Collagen was morphologically normal. Desmosomes, hemidesmosomes, and anchorage fibers were present in areas adjacent to lesions. Ulcerative dermatitis of sows is morphologically similar to pemphigus, pemphigoid, systemic lupus erythematosus, epidermolysis bullosa simplex, erythema multiforme, toxic epidermal necrolysis, and drug eruption. However, significant differences exist between ulcerative dermatitis and these conditions. PMID- 4035940 TI - Microfilarial granulomas in the spleens of wild-caught cynomolgus monkeys (Macaca fascicularis). AB - Splenic nodules from 38 cynomolgus monkeys (Macaca fascicularis) which were captured in Malaysia and Indonesia were studied histologically. The lesions were characterized by well-circumscribed focal fibrosis, accumulation of eosinophils and histiocytes, hemorrhage or hemosiderosis, and loss of normal splenic architecture. Small arteries in the lesion frequently had intimal thickening and narrowing of the lumen in addition to the presence of microfilariae. Microfilariae were also seen in the extravascular area of the lesion, and were occasionally engulfed by multinucleated giant cells. The splenic lesion was thought to have been initiated by incomplete infarction caused by intimal thickening and microfilarial occupation of the small arteries. PMID- 4035941 TI - Pelger-Huet anomaly in cats. AB - Pelger-Huet anomaly was diagnosed in a young male cat on the basis of persistent nuclear hyposegmentation of blood granulocytes, absence of clinical disease or feline leukemia virus infection, and demonstration of genetic transmission of the anomaly. Neutrophils, eosinophils, basophils, and monocytes had significantly less nuclear segmentation when compared to similar leukocyte types from a control cat. On smears of bone marrow, megakaryocytes also appeared hyposegmented. A test mating with an unaffected queen produced a litter of five kittens (three males, two females). One male and one female kitten had the Pelger-Huet trait on examination of blood smears. Autosomal dominant transmission of this anomaly is suspected based on these findings. PMID- 4035943 TI - Experimental onion-induced hemolytic anemia in dogs. AB - Within one day following a single oral dose of dehydrated onions, dogs were found to have large numbers of Heinz bodies within erythrocytes. The percentage of erythrocytes that contained Heinz bodies increased slightly to a maximum on day 3 and then declined. The turbidity index increased more gradually with a maximal value on day 4. Erythrocytes with hemoglobin contracted to one side of the cell (eccentrocytes) also appeared after onion feeding. Eccentrocytes are believed to result from a direct injury to the erythrocyte membrane. As with Heinz body containing cells, the percentages of eccentrocytes present declined as anemia developed. The packed cell volume began to decrease one day after onion administration. A mean decrease of 19 percentage points was reached by day 5. The most anemic dogs had evidence of intravascular hemolysis. Reticulocytosis was first observed five days after onion administration. A slight increase in methemoglobin content was measured four hours after onion administration. No significant changes in erythrocyte reduced glutathione concentration were measured. Transient neutrophilia occurred concomitant with the peak reticulocyte response. PMID- 4035942 TI - Functional and biochemical characterization of immunologically derived equine platelet-activating factor. AB - Antigen-specific challenge of equine leukocytes induced the non-lytic release of a platelet-activating factor in vitro. The equine platelet-activating factor stimulated the release of serotonin from equine platelets in a dose-responsive manner, independent of the presence of cyclo-oxygenase pathway inhibitors such as indomethacin. Rabbit platelets were also responsive to equine platelet-activating factor. The release of equine platelet-activating factor was a rapid reaction with near maximal secretion taking place in 30 seconds. Addition of equine platelet-activating factor to washed equine platelets stimulated platelet aggregation which could not be inhibited by the presence of aspirin or indomethacin. Platelets pre-incubated with equine platelet-activating factor became specifically desensitized to equine platelet-activating factor while remaining responsive to other platelet stimuli such as collagen and epinephrine. The following biochemical properties of equine platelet-activating factor are identical to those properties of 1-0-alkyl-2-acetyl-sn-glyceryl-3 phosphorylcholine (AGEPC): stability upon exposure to air and acid; loss of functional activity after base-catalyzed methanolysis with subsequent acylation that returned all functional activity; and identical relative mobilities on silica gel G plates developed with chloroform:methanol:water (65:35:6, volume/volume). The combined functional and biochemical characteristics of equine platelet-activating factor strongly suggest identity between this naturally occurring, immunologically derived equine factor and AGEPC. PMID- 4035944 TI - Myelopoiesis and marrow adherent cells in estradiol-treated mice. AB - Myelopoiesis and marrow adherent cells were evaluated in C57Bl/6J mice at two and four weeks after treatment with 0.1 mg 17 beta-estradiol cyclopentylpropionate. Estradiol-treated mice were lymphopenic and eosinopenic at two and four weeks; in addition, neutropenia occurred at four weeks. Numbers of lymphoid, granulocytic, and erythroid cells were decreased in the marrow at two and four weeks. The numbers of granulocyte-macrophage and fibroblast colony-forming units in the humeral marrow were also decreased at two and four weeks. However, the hematopoietic ability of marrow adherent cells was unchanged in estradiol-treated mice. Thymic cortical atrophy, metaphyseal osteosclerosis, and neutrophilic infiltration of the uterus occurred in estradiol-treated mice. PMID- 4035945 TI - Enhanced myotoxicity and involvement of both type I and II fibers in monensin tiamulin toxicosis in pigs. AB - Simultaneous administration of monensin and tiamulin to pigs resulted in enhanced myotoxicity. Skeletal muscles of tongue, diaphragm and legs were preferentially affected, whereas the masseter, longissimus thoracis and cardiac muscles, including the left auricle, were spared. Histochemical examination revealed an involvement of both type I and II fibers of skeletal muscles. PMID- 4035946 TI - Meningeal hemangioma and renal hamartoma in a heifer. PMID- 4035947 TI - Renal fibroma in four dogs. PMID- 4035948 TI - Sodium in health and disease: a comparative review with emphasis on herbivores. AB - This review aims to illustrate the relationships between a number of basic and clinical aspects of sodium metabolism with special emphasis on herbivores, particularly ruminants. These animals provide a challenge to some traditional views based essentially on humans, dogs and laboratory rats reared on liberal sodium intakes. Detailed attention is focussed on two central issues; the magnitude of sodium requirement and the relative importance of the kidney and the gut in regulating body sodium. Both provide strong reasons to question accepted beliefs. PMID- 4035949 TI - Establishment of the tropical dog tick, Rhipicephalus sanguineus, in a house in London. PMID- 4035950 TI - Diffuse gangrene of the hindlimb associated with umbilicus infection in a calf. PMID- 4035951 TI - Employment of veterinary surgeons by local authorities in England and Wales. PMID- 4035952 TI - Dog destruction in Northern Ireland. PMID- 4035953 TI - Anal surgery. PMID- 4035954 TI - Stunting syndrome of broilers. PMID- 4035955 TI - Pediatric exposure to the houseplant Synadenium grantii. PMID- 4035956 TI - An indirect hemagglutination test for the detection of antibodies to Clostridium chauvoei. AB - An indirect hemagglutination (IHA) test using sonicated extract as the antigen was developed for the detection of antibodies to Clostridium chauvoei. This antigen can be adsorbed onto glutaraldehyde-fixed sheep red blood cells treated with tannic acid and can be destroyed by trypsin and heat treatment. It corresponded well with the flagella of the organism, when analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and the gel diffusion test. No serological cross-reactivity was found in the IHA test when the antigen was tested against 4 species of clostridial antibodies. Our results suggest that the IHA test mainly detects antibodies against the flagella of C. chauvoei. PMID- 4035957 TI - Properties of an Australian isolate of bovine parvovirus type 1. AB - An Australian bovine parvovirus isolate (BPV 267) was found to haemagglutinate human, guinea-pig, rat and dog erythrocytes, out of a range of 16 species of erythrocyte tested. The haemagglutinating activity was generally found to be both pH and temperature dependent. The virus was found to replicate best in intestinal epithelium, macrophage and lung cells, out of 9 bovine cell types tested. Highest yields of virus were obtained by the use of selected cell strains at low-passage levels which were maintained near neutral pH under conditions of high rates of cell growth. Studies of the rates of thermal inactivation with time showed the virus to be relatively stable at 37 degrees C, 56 degrees C and 70 degrees C, the incorporation of serum proteins, 1 M MgCl2 and 2 M NaCl in the medium having no influence on stability at 56 degrees C. The virus was resistant to the action of CHCl3, ether and 1% trypsin, and its replication was inhibited by BUDR, this effect being reversed by thymidine. Actinomycin D was found to inhibit virus replication, but only when applied during the first 8 h post-infection. Density gradient studies showed infective virus to have a density of 1.41 g cm-3; haemagglutinating non-infective virus with defective morphology having a density of 1.31 g cm-3. In addition, a proportion of morphologically-complete haemagglutinating, but non-infective virus particles was found at a density of 1.36 g cm-3. The virus proved to have a mean diameter of 22 nm. PMID- 4035959 TI - Detection of staphylo-coagulase using plasmas from various animals. AB - The effect of sources of Staphylococcus aureus and plasmas, concentration of plasma, temperature and duration of incubation on coagulase-test results was evaluated. Using S. aureus strains of food origin, the value of plasmas in coagulase tests was, in order of superiority, human and rabbit greater than pig greater than donkey greater than chicken greater than cattle greater than duck greater than goat greater than dog. However, with staphylococcal isolates of animal origin the order was cattle greater than pig greater than human greater than duck greater than goat greater than dog greater than rabbit greater than chicken greater than donkey. Regardless of the source of staphylococci, horse plasma was found unsuitable in coagulase tests as it clotted spontaneously. The temperature (25 and 37 degrees C), and duration of incubation and type of anticoagulant had no significant (P greater than 0.05, X2) effect on coagulase test results. It is concluded that in testing staphylococcal isolates from various sources for coagulase production, it is imperative to use plasmas from several animal species whenever practicable as staphylococcal biotypes display variable ability to coagulate different plasmas. PMID- 4035958 TI - Survival of Corynebacterium renale, Corynebacterium pilosum and Corynebacterium cystitidis in soil. AB - Survival of the causative agents of bovine pyelonephritis, Corynebacterium renale, C. pilosum and C. cystitidis, was examined at 30 degrees C in autoclaved soil. In the soil from a paddock, C. renale and C. cystitidis survived for 56 and 63 days, respectively, and C. pilosum for a longer period of at least 210 days. In soil from a pasture, sand from an athletic field and sea sand, the survival of these bacteria was of shorter duration. PMID- 4035960 TI - [Role of the medical school in military-patriotic education of the younger generation of Soviet physicians]. PMID- 4035961 TI - [Changes in the skeletal system in primary biliary liver cirrhosis]. PMID- 4035962 TI - [Myelography using amipaque in the diagnosis of diseases and injuries of the spinal cord and spine]. PMID- 4035963 TI - [X-ray diagnosis of spinal cord tumors]. PMID- 4035964 TI - [Roentgenometric and microroentgenographic evaluation of regional osteoporosis in a non-load-bearing extremity (experimental data)]. PMID- 4035965 TI - [Primary bone manifestations of lymphogranulomatosis]. PMID- 4035966 TI - [Intraosseous nodes (ganglia)]. PMID- 4035967 TI - [Role of skull x-rays in the differential diagnosis of small intrasellar pituitary tumors]. PMID- 4035968 TI - [Value of serial angiography in the differential diagnosis of pigmented villonodular synovitis]. PMID- 4035970 TI - [Training of medical school students in roentgenoradiology]. PMID- 4035969 TI - [Angiographic diagnosis of impotence]. PMID- 4035971 TI - [Shielding the head of children in x-ray studies]. PMID- 4035972 TI - [X-ray diagnosis of osteopoikilosis]. PMID- 4035973 TI - [Case of intrarenal aneurysm of a congenital solitary left kidney]. PMID- 4035974 TI - [Thyroid lymphography with water-soluble agents in the diagnosis of thyroiditis]. PMID- 4035976 TI - The effects of serum on the in vitro adherence and maturation of bovine monocytes. AB - Serum concentration was found to affect both the initial adherence and subsequent in vitro maturation of bovine monocytes. Bovine monocytes cultured in the absence of serum remained small and reduced in number, whereas monocytes cultured in an adequate concentration of either autologous adult bovine or fetal bovine serum developed into large macrophage-like cells. Heat inactivation (56 degrees C for 30 minutes) did not affect the ability of bovine sera to promote monocyte maturation in vitro. PMID- 4035975 TI - Mitogenic responses of baboon (Papio cynocephalus) peripheral blood mononuclear cells. A possible role for monocytes. AB - Removal of carbonyl iron-adherent/phagocytic cells from baboon peripheral blood mononuclear cells generally resulted in a depressed blastogenic response to both pokeweed mitogen and concanavalin A. In the majority of cases, no alteration in dose requirement nor shift in kinetics was apparent. Staining for peroxidase activity indicated a reduced proportion of monocytes in the population of cells treated with iron. Therefore, the results of this study strongly suggest a potentiating role for monocytes in lectin stimulation of baboon lymphocytes. PMID- 4035977 TI - Isolation of porcine, canine and feline IgG by affinity chromatography using protein A. AB - Isolation of porcine, canine and feline IgG has hitherto been achieved usually by DEAE-ion exchange chromatography and gel filtration. These procedures, however, are rather time-consuming, as they involve purification of IgG. Isolation of IgG by affinity chromatography on a column of protein A-Sepharose was attempted. IgG of all three animal species was very easily isolated with a high yield. In the absence of any other method that allows isolation of IgG of three animal species from a single column, the procedure proposed would be very useful. PMID- 4035978 TI - The role of antibody in protection against African swine fever virus. AB - Intraperitoneal immunization of pigs with anti-African swine fever virus (ASFV) antibody protected them against the effects of challenge with ASFV. This protection, which was exemplified by a reduction in pyrexia and viraemia plus an increased survival time, appeared to be mediated through the effects of complement-dependent antibody-mediated cytotoxicity (CDAC) or antibody dependent cell mediated cytotoxicity (ADCC). Experiments suggested that the reduction in viraemia was associated with complement lysis whereas protection was conferred by ADCC. PMID- 4035979 TI - Serum neutralization of cytotoxin from Pasteurella haemolytica, serotype 1 and resistance to experimental bovine pneumonic pasteurellosis. AB - Sera from several groups of experimental calves were tested for cytotoxin neutralizing capacity. The relationship between this capability and resistance of the animals to an experimental challenge was examined. All undiluted bovine sera tested, other than fetal bovine serum, neutralized cytotoxin. Preadsorption of selected sera with formalin-killed P. haemolytica did not reduce their neutralizing capacity. Crude IgG fractions extracted from bovine sera retained neutralizing capacity as well. Cytotoxin neutralization titers were determined by serial dilution of sera from cattle which were previously unexposed, naturally exposed, or exposed by vaccination to the organism. Both live and killed vaccines were used. Prior exposure to live organisms resulted in the production of antibodies to both cell surface antigens and cytotoxin, whereas exposure to the killed vaccine resulted in the production of antibodies primarily to cell surface antigens. Resistance to experimental challenge with the organism correlated directly with serum cytotoxin neutralizing titers. PMID- 4035980 TI - The immune reactivity of the regional and distant lymph nodes to autochthonous ovine squamous cell carcinomata. AB - Anti-tumor immune reactivity of lymphocytes derived from lymph nodes regional to and distant from tumor growth, as well as that of peripheral blood leucocytes, against autochthonous tumor cells, was investigated. Experiments were carried out in vitro using a 51Cr cytotoxic assay and in vivo by cannulating the afferent and efferent lymphatics of regional and distant lymph nodes and challenging via the afferent lymphatics with 10(7) cultivated autochthonous tumor cells. No anti tumor cytotoxic reactivity was detected in vitro using lymphocytes derived from any of the sources studied. In vivo, while challenge with autochthonous tumor cells produced no response in the regional lymph node, significant blast cell response was obtained in the distant node. The response at the distant node was associated with the production of antibodies that could bind to tumor cells without causing their demise. The anergy observed at the regional lymph node, and the possibility of a relation between the events occurring at that node and those observed at the distant node, are discussed. PMID- 4035981 TI - Phagocytosis of erythrocyte membranes (white ghosts) from different species by the isolated perfused rat liver. AB - Autologous and heterologous erythrocyte membranes (white ghosts) - suspended in a perfusion medium free of immunoglobulins, proteins and hemoglobin - were offered for phagocytosis to isolated perfused livers of different rat strains. The mononuclear phagocyte system of the liver was able to phagocytize these membranes without opsonization. An immunological reaction between Kupffer cells and red cell membranes cannot be excluded, since autologous cell membranes are phagocytized at a higher rate than heterologous cell membranes. PMID- 4035982 TI - A sequential broncho-alveolar washing in non-anaesthetized normal bovines: method and preliminary results. AB - The method of lung lavage under fiberoptic control allowed collection of alveolar cells in non-anaesthetized adult cows. The median section of the diaphragmatic lobe was lavaged with five consecutive aliquots of 30 ml each. Every one was analysed separately. A mean of 25.6% of instilled fluid was recovered and this is lower than amounts obtained on isolated lungs or in anaesthetized calves (about 50%). The cellular formula of 30 samples showed 83.5% of macrophages, 6.0% of lymphocytes, 9.4% of polymorphonuclear cells, 0.5% of monocytes. Cellular viability and total cell count were similar to previously published data. All results were found to be independent of the washing sequence. This simple and well tolerated technique appeared to be a useful tool for the study of defence mechanisms of deep lung. PMID- 4035983 TI - Preliminary study on the use of a silver oxide watch battery (1.5 V) for electrical enhancement of bone healing. AB - A totally implantable watch battery (1.5 V) having 2 cathodes connected with 2 cortical screws of an osteosynthesis plate and one anode in the adjacent tissues gave positive results when used for enhancement of healing in experimentally fractured model. PMID- 4035984 TI - [Use of a concentrated and purified vaccine against chlamydial abortion in sheep]. AB - Attempts were made to immunize sheep against chlamydial abortion with a purified, concentrated, and absorbed vaccine. The latter proved innocuous and unreactive, and was applied at rates of 0.5 to 1.00 cm3. It was found that at a single vaccination of the sheep with 0.5 cm3 as many as 91.42 per cent responded with the production of antichlamydial complement-fixing antibodies on the 45th day of 1:8 to 1:512 titers; 96.43 per cent of the animals responded on the 111th day, the titers ranging from 1:8 to 1:256. At twofold vaccination on the 1st and the 45th day with 0.5 and 1.00 cm3 vaccine, respectively, 100% of the sheep showed antibodies on the 111th day, the titers being within the 1:16 to 1:256 range 49.69 per cent showed antibodies on the 260th day within the 1:4 to 1:512 range. No abortions, stillbirths, and birth of underdeveloped lambs were seen. PMID- 4035985 TI - [Effect of levamisole on white mice and on the immunological reactivity of guinea pigs]. AB - Investigations were carried out on the protective action of therapeutic doses of levamisole (Pharmachim) on mice with a LD100 Salmonella gallinarum infection. Studied was also the effect of levamisole on the immunologic response of guinea pigs infected with Salmonella cholerae suis. It was found that therapeutic amounts of 3 mg/kg levamisole applied to mice following respective patterns protected them against a lethal dose of S. gallinarum. The animals showed enhanced resistance to the infection--20 to 50 per cent of them survived as against 100 per cent mortality with the controls. The guinea pigs showed upon treatment with levamisole certain changes with some of the factors of unspecific response--enhanced phagocytic and lysozyme activity as judged by the development of infection with a S. cholerae suis culture. At the same time the agglutinin titer that substantiated the immunologic response was negligibly changed as compared to the controls. On the base of the results obtained an attempt was made to elucidate the mechanism of the protective action of levamisole. PMID- 4035986 TI - [Microorganisms of the fam. Micrococcaceae in the production and storage of prepackaged veal]. AB - Studies were carried out on the numbers and composition of organisms belonging to family Micrococcaceae in the production and storing of calf meat on a dressing combine supplied with modern equipment. Investigated were a total of 60 samples taken from small cuts of veal of the various carcass parts. The samples were packed either under vacuum or without such, and were studied immediately after cutting in small parts or after storing for 48 and 72 hours at 4 to 6 degrees C. It was found that the amount of Micrococcaceae organisms on the surface of cut meat packed out or in vacuum was within the range of 10(3) up to 10(4)/g, and it was shown to be in close relation to the microbial contamination of the initial raw material. There was no rise of the numbers of micrococci and staphylococci of veal that was cut and packed out of vacuum and kept for 48 hours at 4 to 6 degrees C. At refrigerator storing of veal that was packed under vacuum there was no increase in the microbial numbers at the 72nd hour. This pointed to the advantage of using the introduced technology of packing the meat under vacuum. Micrococcus luteus (56.7%), Micrococcus varians (41.8%), and Staphylococcus saprophyticus (1.5%) were isolated from cuts of veal packed both in and out of vacuum. No pathogenic staphylococci were found. PMID- 4035987 TI - [Morphological changes in the genitalia of culled sheep]. AB - Morphologic studies were carried out on the genital organs of a total of 102 culled ewes in a postestrous season. In some 44.12 per cent there were clearly manifested gross lesions. Endometritis forms accounted for a highest percent- 13.7, followed by uterus pigmentation--12.75 per cent, and hypoplasia of the uterus--11.76 per cent. Histologically, the ovaries presented yellow body cysts- 13.00 per cent, follicular cysts--6 per cent, and chronic salpingitis with hydrosalpinx--19 per cent. PMID- 4035988 TI - [Effect of prolonged concentrate feeding on the digestibility and utilization of feed in weaned lambs]. AB - Two series of balance experiments were carried out by the end of the 2nd and 4th month with a total of 18 weaned lambs divided into three test groups. In the course of 150 days first group animals were offered daily 1200-1500 g of concentrate pellets for the first and second experiment. The lambs of the second group were given 1200-1500 g of concentrate pellets and 300 g chopped wheat straw, and those of the third group were given 800 and 1050 g each of concentrate pellets, and 540 g and 720 g of pellets of whole maize plant containing 40 per cent. Determined is the digestibility of feedstuffs at the end of the 2nd and 4th month. Studied were the values of pH and the content of ammonia gas and volatile fatty acids, the total acidity, and the count of Infusoria in the rumen content. It was found that continuous feeding of high amounts of concentrates produced a negative effect on the fermentative processes in the rumen, reliably lowering the values of pH, ammonia gas, and the total count of Infusoria and reliably raising the amount of volatile fatty acids and the total acidity of the rumen content. Affected was also the digestibility of crude fibers and mineral nutrients. Lowest digestibility of nutrient matter was shown by lambs fed on rations that included concentrate pellets of whole maize plants. It was demonstrated that the continuous intake of high-concentrate rations in which roughage was chopped to 2 mm particles and the amount of crude fibers was lowered to 5.29; 9.6; and 10.8 per cent of the dry matter led to latent metabolic acidosis. The latter could not prevented by the inclusion of 300 g chopped wheat straw and 540 and 720 g of pellets of whole maize plant. PMID- 4035989 TI - [Effect of feeding on fertility]. PMID- 4035990 TI - [Immunoprophylaxis of listeriosis in sheep with a killed vaccine]. AB - Experiments were carried out with 20 young ewes, 20 rabbits, 20 guinea pigs, and 10000 sheep and lambs, using a killed vaccine of Listeria 1 and 4c with heat under the protection of antidenaturation agents. Bacteriologic, histologic, and histochemical investigations and lung macrophage cultures were used to establish the changes in untreated, vaccinated, and challenged vaccinated animals. Listeria organisms from the challenged animals were isolated in sporadic cases from the barin and viscera, while from untreated and infected animals such organisms were isolated during the entire period of investigation. The use of cultures demonstrated the part played by cell immunity as early as the 3rd to 7th day following vaccination. It was found that the vaccine inhibited the development of pathologic lesions of intoxication in the body and led to the immunologic rebuild of animals. The vaccination of both sheep and lambs in herds with listeriosis suppressed the disease and the mortality thereof. PMID- 4035991 TI - [Changes in the blood indices of turkey poults experimentally infected with Eimeria adenoides]. AB - Studied were the changes in the values of sodium, potassium, chlorides, calcium, phosphorus, iron, and copper in the blood plasma as well as in that of hemoglobin, hematocrit, and the total count of blood cells in turkey poults experimentally infected with Eimeria adenoeides. The birds were divided into three groups of 40 each. The first and second were infected with various numbers of sporulated oocysts, while the third group was kept as a control one. It was found that Na, chlorides, Ca, P, and Fe were lowered, and K and Cu were increased over the same period. The total blood cell count and the hematocrit rose on the 4th and 5th day following infection, while they dropped on the 6th to the eighth day. The same was true of hemoglobin values. PMID- 4035992 TI - [Enterohepatic cycle of bile acids and erythrocyte survival]. AB - A comparative analysis is made of the correlation between the life of erythrocytes in various species of animals and some parameters of the gallbladder and its secretion. Due attention is paid to the presence of the bladder, its size, and the concentration and intensity of secretion as well as to the effect of the various bile components on the surface tension of water, the water solution of salts, and the erythrocyte membrane. It is believed that both the composition of bile and the structure of erythrocyte membrane are homeostatically determined. It has been found that the mechanism of aging, resp., the preparation of the phagocytosis of erythrocytes proceeds as acted upon by the bile secretion, and that this process runs its course through the enterohepatic cycle of bile acids in the portal circulation. PMID- 4035993 TI - [Pathogenic role of O. venulosum in lambs]. AB - Studied was the effect of an experimental infection of lambs with 1000 and 4000 larvae of Oesophagostomum venulosum on the activity of some more important serum enzymes, the level of sulfhydryl groups, and the level of sugar. It was found that the activity of glutamic acid oxal-acetate transaminase and lactic acid dehydrogenase rose, and that of alkaline phosphatase dropped. At 4000 larvae the level of glutamic acid pyruvate transaminase rose. The concentration of blood sugar dropped. There was also a drop of the SH groups. It was best manifested from the first to the third week following infection. In the fourth week the level of the total and residual SH groups showed a trend toward coming back to normal, however, the initial values were not reached. PMID- 4035994 TI - [Method of demonstrating and determining glyphosate in biological matter]. AB - A method was worked out for the extraction of glyphosate from plant and biologic material originating from experimentally treated terrains, animals, and birds. The 'sensitivity' of a number of developers was comparatively studied--used either alone or in combination, choosing the most effective one. It was found that the most proper mobile phase consisted of ethanol : ammonia gas : distilled water in a 1:1:1 ratio and a 0.3 per cent alcohol solution of ninhydrin with a following heating in a kiln at 105 degrees C in the course of 3 to 5 min, with a use of aluminium plaques (Merck production). It is concluded that the method could be employed in all labs as it is highly specific (0.0004 mg glyphosate) and does not require special apparatus. PMID- 4035995 TI - [Morphological and biochemical changes in the blood of lambs with experimental Erysipelothrix polyarthritis]. AB - Polyarthritis was induced in lambs via the i/v infection with 2 cm3 of 24-hour Erysipelothrix rhusiopathiae broth culture, which led to distinctive morphologic and biochemical changes in the peripheral blood. The hemoglobin content, the erythrocyte count, and the hematocrit value dropped, while ESR rose with the development of the infection process. The white blood picture presented transient and slight drop of the leukocyte count followed by leukocytosis with shifting to the left, aneosinophilia, lympho- and monopenia in the acute stage, and well manifested eosinophilia in the chronic stage of the infection. The changes in the total protein and the protein fractions consisted in hypoproteinemia in the first days following infection, hypoalbuminemia during the entire period, and hyperproteinemia and hypergammaglobulinemia in the chronic stage. The changes in the blood electrolites consisted in the rise of Ca and K, the drop of Na, and transient changes in the level of P, tending toward a rise in the chronic stage. It was also established that the values of sialic acid were raised in the entire period of polyarthritis development, while those of aspartate aminotransferase and alanine aminotransferase were higher in the first seven-day period only. PMID- 4035996 TI - [Changes in the ECG telemetry of lambs infected with Cysticercus ovis]. AB - Six lambs were experimentally infected with Cysticercus ovis. Some changes were followed up in the ECG by means of the radiotelemetric method. The infection process led to the following more important changes, such as sinus tachicardia and arhythmia, auricular fibrilation, sinoauricular block, atrial dissociation, the incidence of a pathologic Q deflection; lowering of the R deflection amplitude, and inversion of the T wave. It was found that the changes referred to persist for a longer period (in the case of infarction), and could be made use of in dispensary studies. PMID- 4035997 TI - [Production of enterotoxins A, B and C in staphylococcal strains isolated from animal food products and other sources]. AB - Studies were carried out on the production of enterotoxins A, B, and C by a total of 654 strains of Staphylococcus aureus. Of these, 326 were isolated from food products of animal origin (and had no connection with intoxications); 190 were isolated from personnel working in the food industry; and 138 were isolated from milk animals, containers, and equipment at productional enterprises. Thirty strains of S. epidermidis, isolated from food products and workers were likewise tested for the production of the same enterotoxins. The enterotoxins were obtained by the modified method of Hallander, and their demonstration was performed by a variant technique of the double gel diffusion test after Ouchterlony. It was found that the Staphylococcus aureus strains isolated from food products produced enterotoxins in 12.3 per cent of the cases; was found in 6.1% of the strains, C--in 3.1%, and B--in 2.5%. Types A and C were found simultaneously in 0.6% of the strains. Enterotoxins were found in 16.6% of the strains isolated from workers and in 1.7% of those isolated from the udder of cows. The incidence of toxin production and the relative share of the three types of enterotoxins depended on the origin of staphylococci and their capacity to produce them in amounts that could be demonstrated by the methods employed. Under optimal conditions the amounts varied: for strains that produced type A they ranged from 1 to 20 micrograms/cm3; for those that produced type B they were from 1 up to 100 micrograms/cm3; and for those that produced type C they were from 1 to 40 micrograms/cm3. No production of enterotoxins A, B, and C was established with S. epidermidis strains. PMID- 4035998 TI - [Microbiological research on the production and storage of fast-frozen semiproducts]. AB - Studies were carried out to find the sources of microbiologic contamination, and the quantitative and qualitative composition of microflora and its changes following various periods of storing of rapidly frozen meat-balls obtained under productional conditions. The investigations were performed with regard to the total count of aerobic organisms, coli forms, staphylococci, sulfite-reducing Clostridia, Salmonellae, and moulds. It was established that the machines, equipment, units, and package had no effect on the bacteriologic contamination of meat-balls. Storage at--18 degrees C in the course of six months had no effect whatever on the residual microflora and the organoleptic indices of this product. It is stated that the standard requirements concerning the total numbers of anaerobic mesophilic organisms should not exceed 5 X 10(3)/g at a coli titer of 1.0. PMID- 4035999 TI - [Amino acid composition of white poultry meat contaminated with psychrophilic microorganisms]. AB - Studied was the effect of psychrophilic organisms of the Acinetobacter, Aeromonas, Alcaligenes, and Flavobacter genera on the amino acid composition of white poultry meat stored at 0 degrees to 4 degrees C in the course of 48 hours, and at 18 degrees C in the course of 6 to 12 months. The quantitative determination of individual amino acids was carried out by means of an automatic amino acid analyzer, Hitachi type, after the method of Speckman, Stein, and Moore. No changes were established in the amino acid composition of white poultry meat that was treated with psychrophilic organisms as against the composition of untreated meat. Proteins preserved their biologic value. PMID- 4036000 TI - [Experimental deratization on a commercial swine-breeding farm]. AB - Continuous eighth-month deratization was carried out on an industrial swine breeding complex, having great numbers of the black rat (R. rattus). Anticoagulants were chiefly used, maintaining permanent sites of poisonous baits. The lowering of rat numbers was followed up at two-month intervals in the individual productional sectors. Some indices were determined, such as intensiveness, extensiveness, and effectiveness. It was found that each of these indices characterized particular aspects of the deratization process on the complex as a whole and in the various sectors. A suggestion is made to use all indices in combination in assessing the effect of deratization on such complexes, particularly when due attention is to be paid to the epizootic importance of deratization. With regard to the economic effect it has been established that even with uninterrupted process of deratization for a long period of time on the entire area of a swine breeding complex this measure is economically expedient. Great amounts of valuable feed are economized owing to the lower number of rodents. PMID- 4036001 TI - [Methodological problems in researching chemical substances for their embryotoxic, teratogenic, hypotrophic and gonadotoxic action on agricultural animals]. AB - The methodical problems in the study of chemicals with toxic, teratogenic, hypotrophic, and gonadotoxic effects on farm animals are tackled for the first time. With lab animals some new methodical interpretations are introduced in studying these chemical aftereffects with regard to farm animals. Determined has been the most sensitive animal species which can be used in such investigations. With sows it is suggested to perform cesarean section on the 50th or 80th day from the beginning of pregnancy, and not on the 1st or 2nd day prior to farrowing. With sheep the same is to be done on the 60th or 90th day. A method is also to be employed concerning a two-step successive castration with one and same animal. It makes it possible to follow up the dynamic of the effect of chemicals on the sexual function and the response of the germinative tissue in the processes of adaptation, compensation, and compensatory hyperfunction and hypertrophy. PMID- 4036002 TI - Immunological investigations in inbred mice chronically infected with cytopathogenic agents isolated from human cases of Balkan endemic nephropathy. AB - An experimental chronic infection was induced in inbred A2G and CBA mice by repeated administration of four cytopathogenic agents isolated from human cases of Balkan endemic nephropathy (BEN). The slight humoral and cell-mediated immune responses to the BEN agents recorded in A2G mice were associated with autoimmunity and hypersensitivity phenomena. In contrast, the normal, intense immune response observed in CBA mice was not accompanied by any immunopathological changes. In both mouse lines the chronic infection with human BEN agents led to a secondary immune deficiency against sheep red blood cells or tuberculin. PMID- 4036003 TI - Efficiency of the NIVGRIP inactivated influenza vaccine applied by oral route: evaluation in a community of pre-school children in the period 1981-84. AB - The NIVGRIP inactivated influenza vaccine prepared in the "Stefan S. Nicolau" Institute of Virology was administered by oral route to 3-6-year-old children of a preschool community in October 1981, 1982 and 1983. There were no cases of acute respiratory tract infection (ARTI) in the community in the winter seasons of 1981-82, 1982-83 and 1983-84, with the exception of 3 ARTI cases recorded in February 1982 in unvaccinated children. In a similar community where no vaccination had been performed morbidity by ARTI was of 20% in 1982-83 and 12.6% in 1983-84. The efficiency and the advantages of oral influenza vaccination are outlined. PMID- 4036004 TI - The effect of an aqueous horse-radish extract, applied as such or in association with caffeine, on experimental influenza in mice. AB - An aqueous horse-radish extract was repeatedly administered to mice by intranasal (i.n.) route prior to i.n. inoculation of influenza virus A/PR8/34 (H1N1). The antiviral effect of the extract--also demonstrated in vitro--was reflected by a significant decrease in the hemagglutination titers recorded in mouse lung homogenates and by a slight increase in the mean survival time of treated mice versus untreated controls. Association of horse-radish extract with caffeine led to a synergic effect only as regards the mortality rate. PMID- 4036005 TI - Evolution of the A/Chicken/Pennsylvania/83 (H5N2) influenza virus. AB - The epidemiological features of the H5N2 outbreak of influenza in poultry were studied by sequencing the HA genes of several viruses isolated during the epidemic. Comparison of the nucleotide sequences of the HA genes indicated there was a single introduction of virulent virus. The variation rate (silent mutations) in the HA gene of the virulent Ck/Penn virus was 9.0 or 14.4% per 10 years depending on the viruses compared and was similar to that in H3 HA gene of human influenza A virus. The virulent and avirulent viruses isolated after October 1983 were derived from a common ancestoral virus and the virulent virus did not supersede the avirulent virus, instead, the virulent and avirulent viruses coexisted and evolved separately during the course of the epidemic. The evolutionary changes in the HA of H5N2 viruses that occurred during the epidemic permitted us to establish that a virus (A/Chick/Washington/84) that was isolated 8 months after the last H5N2 virus had been isolated from poultry in Pennsylvania belonged to the family of potentially dangerous H5N2 viruses and was a direct descendent of the virus that spread to Maryland and Virginia. All of the virulent Ck/Penn viruses retained the amino acid changes at residues 13 and 69 in the HA. PMID- 4036006 TI - Thermal stability of cowpea mosaic virus components: differential scanning calorimetry studies. AB - Differential scanning calorimetry studies show that the thermal stability of cowpea mosaic virus (CPMV) is pH dependent in the pH range 5 to 8. The four different components of CPMV, top (protein shell devoid of RNA), middle (virus particle containing the smaller RNA), bottom upper and bottom lower (virus particle containing the larger RNA), are stable up to 64-70 degrees at pH 5.0 and up to 43-46 degrees at pH 8.25. These components did not exhibit any difference in their thermal stability between pH 6.0 and 8.0. PMID- 4036007 TI - Virulent mutants of bacteriophage phi80. AB - We have characterized a collection of 11 phi80 mutants that develop in wild-type lysogenic hosts ("virulent" phenotype). All these carry gross DNA rearrangements affecting the right arm of the phi80 chromosome. Our results are consistent with the notion that phi80 development is negatively controlled by the ineA gene product, encoded by one of a cluster of genes (phi80 immunity) located between the phi80 replication and recombination genes. We describe and assign positions for ineA and other genes within the immunity region. PMID- 4036008 TI - [Toxic effects of isoprenaline on embryonic heart muscle--the effect of beta blockers and calcium antagonists]. PMID- 4036009 TI - [Use of desmopressin (DDAVP) in the detection of decreased fibrinolytic capacity in persons with idiopathic venous thrombosis and myocardial infarct at a young age]. PMID- 4036010 TI - [Surgical treatment of post-infarct aneurysms of the left ventricle of the heart]. PMID- 4036011 TI - [Long-term experience with intra-aortic balloon counterpulsation]. PMID- 4036012 TI - [15-year study of the pre-hospital phase in acute myocardial infarct in the Most District]. PMID- 4036013 TI - [Angina pectoris in women of reproductive age]. PMID- 4036014 TI - [Treatment of resistant, recurrent paroxysmal tachycardias-- contribution of amiodarone]. PMID- 4036015 TI - [Reduction of the calcium level in bones in ischemic heart disease]. PMID- 4036016 TI - [Changes in renal excretion of amino acids in patients after portasystemic anastomoses]. PMID- 4036017 TI - [Deviations in cholesterol metabolism as a risk factor in patients with chronic glomerulonephritis and with polycystic kidney]. PMID- 4036018 TI - [Experimental chronic pulmonary hypertension in laboratory animals]. PMID- 4036019 TI - [Antimicrobial prophylaxis and therapy and microbiological findings]. PMID- 4036020 TI - [Relation of apolipoproteins, lipoproteins and lipids in a fat loading test]. PMID- 4036021 TI - [The dipyridamole test. Its place in the functional diagnosis of coronary insufficiency]. PMID- 4036022 TI - [Is the administration of nifedipine to asthmatics without danger?]. PMID- 4036023 TI - [Ketoconazole in the prevention of mycotic complications during cytostatic treatment of leukemias and lymphomas]. PMID- 4036024 TI - [Systemic amyloidosis associated with plasmacytoma. I. Present etiopathogenic findings]. PMID- 4036025 TI - [Medical and social problems in the care of diabetics--results of a study of 269 patients]. PMID- 4036026 TI - [Preparation of a prothrombin complex concentrate (use of DEAE-cellulose and DEAE sephadex)]. PMID- 4036027 TI - [Diagnosis of diabetes and evaluation of the oral glucose tolerance test according to the recommendations of the World Health Association, 1980]. PMID- 4036028 TI - [Congenital heart defects in adulthood]. PMID- 4036029 TI - [Post-exertional electromapping in the diagnosis of ischemic heart disease]. PMID- 4036030 TI - [The composition of skeletal muscle--an important factor in the pathogenesis of obesity in men]. PMID- 4036031 TI - [The HLA system and changes in thyroid hormones in patients]. PMID- 4036032 TI - [Use of the single-dimension echocardiographic examination (a scan) in the diagnosis of thyroid gland diseases. Comparison with scintigraphic and puncture findings]. PMID- 4036033 TI - [The relation of HLA to disease. What is the most reliable way to determine its significance?]. PMID- 4036034 TI - [At the present level of anticoagulation therapy with Pelentan, is it possible to expect effective prevention of thromboembolism?]. PMID- 4036035 TI - [Treatment of ulcer disease using H2 antihistaminics]. PMID- 4036036 TI - [Philosophical bases of the study of normal clinical values]. PMID- 4036037 TI - [Organization and methods of conducting a special medical tactical exercise with the regimental medical aid station]. PMID- 4036038 TI - [Characteristics of the medical support for small units in field exercises and operations in a mountainous desert area]. PMID- 4036039 TI - [Hospital infection]. PMID- 4036041 TI - [Hyperbaric oxygenation in combined therapy of viral hepatitis]. PMID- 4036040 TI - [Therapeutic effectiveness of correcting potassium metabolism in acute poisoning by organophosphorus compounds]. PMID- 4036042 TI - [Ethical norms and deontological principles in conducting a health inspection]. PMID- 4036043 TI - [Use of a method for self-evaluation of a pilot's psychophysiological status in prolonged flight]. PMID- 4036045 TI - [Let us improve preventive and therapeutic diagnostic work]. PMID- 4036044 TI - [Effect of a motor regimen on the physical work capacity of sailors during the postcruise rest period]. PMID- 4036046 TI - [Use of adaptation to the conditions of medium-height mountains as a means of secondary prevention of ischemic heart disease]. PMID- 4036047 TI - [Hemocoagulation status during the use of drug hydroaeroionization in the complex treatment of patients with transient cerebrovascular disorders]. PMID- 4036048 TI - [Use of the method of electromyographic feedback with an assessment of the pull of an individual muscle in the early rehabilitation of patients with flaccid paralysis]. PMID- 4036049 TI - [State of the neuromuscular system in patients with scoliosis during adaptation and complex sanatorium-health resort treatment]. PMID- 4036051 TI - [Efficacy of health resort treatment of secondary infertility following tubal pregnancy]. PMID- 4036050 TI - [Effect of balneotherapy on the functional state of the cardiopulmonary system in children with scoliosis]. PMID- 4036052 TI - [Experimental study of the activity of the myometrium as affected by mineral waters]. PMID- 4036053 TI - [Therapeutic gymnastics, massage and self-massage in dermatological practice]. PMID- 4036054 TI - [Composition and properties of mineral waters in storage]. PMID- 4036055 TI - [Theories of the reflex mechanism of action of physical factors and functional systems of the body]. PMID- 4036056 TI - [Evaluation of the anti-inflammatory action of lipids from therapeutic mud silts]. PMID- 4036057 TI - [Change in immunity indices in patients with nonspecific aorto-arteritis as affected by RF-therapy]. PMID- 4036058 TI - [Effect of vitamin E electrophoresis on lipid peroxidation and antioxidant system of the blood in patients with ischemic heart disease]. PMID- 4036060 TI - [Staged treatment of patients with rheumatoid arthritis at a health resort with sulfide waters]. PMID- 4036059 TI - [Use of dry-air radon baths at the sanatorium stage of rehabilitation of patients with rheumatoid arthritis]. PMID- 4036062 TI - [Methods for improving the process of teaching physiotherapy in the internal medicine department]. PMID- 4036061 TI - [Determination of the nature of vascular reactions to the action of helium-neon laser radiation using an otorheographic method]. PMID- 4036063 TI - [Use of physical factors in the late postoperative period after surgical treatment of ischemic heart disease]. PMID- 4036064 TI - [Work of the United Nations Scientific Committee on the Effects of Atomic Radiation]. PMID- 4036065 TI - [Neuroendocrine (Merkel cell) skin cancer. Electron microscopic study]. AB - The study is concerned with the results of light and electron microscopic examination of 2 cases of neuroendocrine (Merkel cell) carcinoma of the skin. Both patients developed multiple widely-distributed intra- and subcutaneous nodules. Histologically, tumors were mostly trabecular. Electron microscopic examination revealed neuroendocrine secretory granules, small bundles of intermediate fibers, a well-defined Golgi complex and a relatively high level of vesicular structures. There were some basal membrane fragments. It is suggested that they originate from polypotential epithelial stem cells. PMID- 4036066 TI - [Value of thyroid lymphography in diagnosing thyroid cancer]. AB - The results of thyroidlymphography carried out in 122 patients with thyroid cancer and 82 cases of benign tumor were analysed. Reliable thyroidlymphographic criteria of malignancy were established on the basis of a comparison of roentgenomorphologic and statistical findings. The significance of the said criteria for making timely diagnosis of cancer with concomitant adenomatosis and chronic thyroiditis is discussed. PMID- 4036067 TI - [Amplification of nucleotide sequences homologous to the viral myc oncogene in DNA of colonic mucosa in a patient with cancer of the same location]. AB - Genomic DNA of intact colonic mucosa obtained from a female patient suffering colonic cancer revealed amplified nucleotide sequences (multiple copies) related to viral myc oncogene. The study failed to detect amplification in tumor. Causation and pathways of the event are discussed. PMID- 4036068 TI - [Modifying effect of thyroid gland functional disorders on realization of transplacental carcinogenesis induced by N-nitrosomethylurea in rats]. AB - The paper discusses the influence of deranged function of the thyroid (in postnatal period) on the transplacental carcinogenic effect of N nitrosomethylurea (NMU) in albino noninbred rats. It was found that exogenous thyroxin-induced hyperthyroidism and thyroid function suppression either by long term treatment with a thyreostatic agent--methylthiouracil (MTU) or thyroidectomy are followed by a lower frequency of, chiefly, nervous system tumors which are typical of NMU-induced transplacental carcinogenesis in rats. Moreover, transplacental treatment with NMU potentiated the carcinogenic effect of MTU on the thyroid. The latter manifested itself in a higher frequency of malignancies of the thyroid in animals exposed to a combined treatment with NMU (transplacentally) and MTU (postnatally) as compared with those given MTU only (postnatally). PMID- 4036069 TI - [Age-related changes in adenylate cyclase activity, lipid composition and lipid peroxidation in rat intestinal mucosa: comparison with the frequency of spontaneous tumors]. AB - The study used 3, 7, 16 and 22 month-old male rats bred at the animal farm of the Institute. Identical age-related changes were established in the level of free cholesterol, its esters, free cholesterol/phospholipids and sphingomyelin/lecithin ratios in ascending and descending colon mucosa. Unlike descending colon mucosa, the basal and hormone-stimulating activity of adenylate cyclase and rate of lipid peroxidation in the mucosa of the ascending colon of 22 month-old animals were lower than in 16 month-old rats. The results are compared with the available data on the predominant localization of spontaneous tumors in the proximal (ascending) part of rat's intestine. PMID- 4036070 TI - [Long-term follow-up of a patient after resection and radiotherapy of a metastasizing testicular teratoblastoma (case report)]. PMID- 4036071 TI - [Liver exocrine function in patients after gastrectomy for peptic ulcer]. AB - Exosecretory liver function was studied in patients after gastric resection for peptic ulcer. Disorders of the biochemical composition of the bile were discovered; they were manifested by disproportional formation and secretion of the basic components of the bile: cholic acid, cholesterol and phospholipids, which led to the shift in the bile components ratio and could promote their precipitation. Moreover, the lowering of the content of the basic components of the bile is likely to bring about a substantial derangement of the processes of fat digestion. Dietetic management of these patients exerted a beneficial effect on cholic acid secretion. However, in some patients with grave postoperative syndromes and disturbances in the hepatobiliary system, no noticeable positive results were obtained. The latter circumstance allows the conclusion about the necessity of placing such patients on prolonged treatment including bile expelling agents. PMID- 4036072 TI - [Effectiveness of using Maliutka and Malysh adapted propionic-acidophilus mixtures in the combined treatment of congenital hypotrophy]. AB - The physical and psychomotor development, immune responsiveness, and intestinal microflora were studied in 82 infants with congenital hypotrophy depending on the nutrition pattern. It was shown that children who received the propionic acidophilic mixtures Malyutka and Malush manifested the highest daily weight gain, the most rapid disappearance on the manifestations of food allergy, an increase in immune responsiveness. A decrease in the cultivation rate of Proteus vulgaris and pathogenic staphylococcus, as well as an increase in the cultivation of bifidobacteria. The data obtained permit recommending the use of the propionic acidophilic mixtures Malyutka and Malysh in combined treatment of children with congenital hypotrophy. PMID- 4036073 TI - [Amino acid metabolism in liver tissue during the consumption of qualitatively different proteins]. AB - To evaluate changes in the liver ability to metabolize amino acids during intake of different proteins, the content of free amino acids was measured in the blood of the portal and liver veins of rats fed krill protein and casein. After 48 h of fasting the animals were given a suspension of krill protein and casein at a rate of 540 mg protein per 100 g bw. After 0.5, 1, 3 and 6 h the content of free amino acids was measured in the blood of the portal and liver veins by ion exchange chromatography with the use of an automatic amino acid analyzer. Administration of krill protein brought about a high enough (63%) absorption of amino acids by the liver during the 6-hour experiment. The degree of casein absorption was 31%. As compared to casein, intake of krill protein led to an earlier saturation of the body with amino acids having branched chains (P less than 0.05). The enzymatic systems of amino acid metabolism responded to the supply of the proteins under study in the same manner, however the rate of adaptation was different, amounting to 0.5 h for krill protein and to 3 h for casein. It is evident that the enzymatic systems involved in amino acid metabolism respond to the intake of krill protein to a larger extent than enzymes involved in metabolism of casein amino acids. PMID- 4036074 TI - [Effect of the quality of dietary protein on the degree of its metabolization in the body]. AB - The authors studied the effect of postponed enrichment of low-grade protein (gluten) by the limiting amino acids (lysine and threonine) on the intensity of the cellular protein synthesis and on the PER. It was established that the rate of incorporation of the labeled amino acid 14C-leucine into cellular proteins changes parallel with change in the PER. Low-grade protein nutrition has an adverse effect on the metabolism. If the diet containing low-grade protein is supplemented with amino acids, the intensity of metabolic processes rises almost to the level seen during adequate animal protein nutrition. A direct and statistically significant correlation was found between the biological value of the protein consumed and the intensity of protein biosynthesis in the cells. It is concluded that measurement of the intensity of the cellular protein synthesis in a good biological test for determination of the test protein quality. PMID- 4036075 TI - [Effect of amino acid deficiency on bone tissue growth and formation]. AB - Intake of the essential amino acids, threonine, lysine and methionine by Ukrainian children of different height was studied. The processes of osteogenesis and phosphorus-calcium metabolism in rats with the above amino acids deficiency in the diet were also subjected to study. A direct correlation was established between intake of the amino acids under study and the height of schoolchildren. The deficiency of the amino acids in the diet of experimental animals contributed to the retardation of the growth, destructive changes, an increase in the content of hydroxyproline, a reduction of phosphomonoesterase-I activity in bones, and alterations in phosphorus-calcium metabolism. PMID- 4036076 TI - [Vesicular transport of nutrients in the small intestine during natural feeding]. AB - Ultrastructural aspects of the absorption of nutrients by the rat small bowel under natural feeding and administration of a food mixture homogenate to a small bowel strip were studied. It is shown that as early as 25 min after the onset of feeding, nutrients get into the proximal part of the small bowel, run across the epithelial barrier and enter the stroma of the intestinal villi and the vascular bed. Active absorption of nutrients is also observed in situ under limited intracavitary hydrolysis. The identified nutrients penetrate the apical membrane of enterocytes by pinocytosis, are detectable but inside vesicular structures of the cell, and get into the intercellular space by exocytosis. The concept of the existence of the control systems preventing foreign substances from penetration in the body and eliminating the sequels of such a penetration has been worded. PMID- 4036077 TI - [Effect of pro- and antioxidant food factors on macrophage oxidative metabolism]. AB - The effects of vitamin E deficiency and excess polyunsaturated acids in the diet on luminol-dependent chemiluminescence were studied in Aug-Lac rats. It was chown that experimental prooxidant regiments led to the increase of oxidative metabolism in macrophages stimulated by opsonized zymozan. Vitamin E deficient regimens decreased superoxide dismutase activity of macrophages. In vitro DL alpha-tocopherol and the synthetic antioxidants BHT and BHA inhibited chemiluminescence of macrophages. Arachidonic acid activated macrophages and induced the formation of oxygen radicals. PMID- 4036078 TI - [Use of computers in studying the actual nutritional and health status of children]. AB - The authors have devised a pack of applied programs for statistic data treatment, which can be used for studying problems of nutrition and the health status of children, for design of rational diets by the research institutes and childhood establishments sponsored by the public health and education systems, as well as by trade unions. PMID- 4036079 TI - [Toxicological characteristics of acute and subacute T-2 mycotoxicosis in mice]. AB - Intragastric administration to mice of solutions of crystalline T-2 toxin in a dose aqual to the LD50 or in doses from the 1/5 to 1/50 of the LD50 brought about a stable decrease in alkaline phosphatase activity and lysozyme concentration in blood serum. In addition, acute and subacute T-2 mycotoxicoses were characterized by a marked lowering of hemoglobin concentration, the total red cell and leukocyte counts (doses 1/5-1/20 of the LD50) and lymphosytes (doses 1/5-1/50 of the LD50) in the peripheral blood toward the end of experiments. Variation of the hematological and biochemical characteristics after administering the toxin in low doses was detected despite the absence of the clinical symptoms of intoxication. These characteristics are the most sensitive to the toxic action of T-2 toxin. PMID- 4036080 TI - [Changes in the excretion of uric acid and urine pH as affected by the diet therapy of patients with gout and uric acid diathesis]. PMID- 4036081 TI - [Principles of organizing nutrition for miners in sanatoria and preventoria]. PMID- 4036082 TI - Immune function in blood donors following short-term lymphocytapheresis. AB - Lymphocyte losses occur during repeat plateletpheresis and/or leukapheresis procedures and are potentially harmful to normal host immune function. This concern prompted us to study the effect of repeat lymphocytapheresis (lymphapheresis) on the immune system of healthy blood donors. Following a total of six lymphapheresis procedures over a 12-day period with removal of a mean of 41.6 X 10(9) lymphocytes, there were no significant changes in donor (n = 5) absolute lymphocyte counts, quantitative immunoglobulin levels or immune response capability as assessed by the following in vitro assays: percent of E, EA, and EAC rosette-forming cells, the percent of surface membrane immunoglobulin bearing cells, and the blastogenic responses to stimulation with phytohemagglutinin, pokeweed mitogen and concanavalin A. The procedures were well-tolerated without complications. During a follow-up period of 18 months, significant increases in total white cell counts (but not absolute lymphocyte counts), and in quantitative immunoglobulin levels (IgG, IgM, and IgA) were observed. The median increases in immunoglobulin levels ranged from 27.5% for IgG to 44% for IgA. We conclude that lymphapheresis as described is relatively safe and our results are reassuring in relation to lymphocyte losses that may occur during repeat cytapheresis procedures of normal blood donors. PMID- 4036083 TI - The second example of anti-K22 and a family genetically informative for K and K22. AB - The second example of anti-K22 was found, like the first, in an Iranian Jew living in Israel. The consanguineous parents of the propositus were both K+k+, and investigation of the family suggested that K22 is controlled by the Kell locus; K travelling with K22 and k with K-22. PMID- 4036084 TI - Successful treatment of post-transfusion purpura with high dose immunoglobulins after lack of response to plasma exchange. AB - A 77-year-old woman with post-transfusion purpura failed to respond to two 2.5 litre plasma exchanges with albumin as a replacement fluid. However, intravenous infusion of high-dose human immunoglobulin produced a response within 4 h. It is suggested that plasma exchange and exchange transfusion are effective in this condition mainly because they have allowed large doses of immunoglobulin to be infused in the form of plasma or whole blood. PMID- 4036085 TI - ISBT Working Party on Terminology for Red Cell Surface Antigens: Munich report. PMID- 4036086 TI - Cell surface alterations during blood-storage characterized by artificial aggregation of washed red blood cells. AB - Aggregation measurement of washed human erythrocytes (RBC) were carried out in a NaCl-PBS solution under laminar shear conditions. Artificial aggregation of fresh and stored erythrocytes was caused by decreased pH and reduced ionic strength and characterized by collision efficiency alpha. Generally, the collision efficiency alpha of stored erythrocytes rises with the increased storage time. Such an aggregation technique might be useful to detect and quantify changes of the membrane and/or the surface structure due to aging and/or storage. PMID- 4036087 TI - [Diabetes mellitus with atrophy of the mm. interossei of the upper extremities]. AB - Two cases are described with atrophy of the interosseous muscles of the upper extremities as a manifestation of peripheral diabetic polyneuropathy with a main motor damage. In both cases, a long-term diabetes is concerned--insulin independent type, perorally treated. Retino- and nephropathy were present in the patients as well as macroangiopathy in one of the cases. The lesions were in the frame of generalized polyneuropathy of the four extremities, confirmed, in one of the cases, by electromyographic examination. No changes in muscular atrophy were observed by the treatment carried out. PMID- 4036088 TI - [Case of severe hypercalcemic crisis in primary hyperparathyroidism]. AB - A patient is described, admitted to the clinic with manifested picture of severe hypercalcemic crisis. The clinical, paraclinical and instrumental investigations established the presence of adenoma of parathyroid glands. In spite of the reduction of hypercalcemia, after the conservative treatment, the effect was but only transient and adenectomy was performed as a radical method, which led to permanent normocalcemia. PMID- 4036089 TI - [The somatotype and fatty body weight of medical students]. AB - The somatotype was determined of 247 healthy students of medicine, male Bulgarians, average age 22, according to the method of Heath and Carter. More than half of the examined subjects (55,9%) was established to belong to the group of mesomorphy with a predomination of the subgroup of endomorphic mesomorphy. The other morphological structures are presented in comparatively identical shares. The fatty body mass, being 16,29 per cent of the total body mass of the subjects studied was determined to the same subjects according to the method of Mohr and Milev. It was established that the fatty body mass was within the physiological limits among the students from the group of ectomorphy and from the group with balanced mesomorphy, non-manifested obesity had the subjects with ectomorphic endomorphy, endomorphic mesomorphy and with central somatotype and with manifested obesity--the students with balanced and mesomorphic endomorphy. PMID- 4036090 TI - [2,3-diphosphoglycerate level during the active and maintenance treatment of iron deficiency anemia patients]. AB - The objective of the present study was to obtain information about the duration of tissue hypoxia in patients with iron deficiency anemia. That fact is of importance for the determination of the duration of maintenance iron therapy. The level of 2,3-diphosphoglycerate was studied during the treatment, after the correction of anemic syndrome and after 60-day out-patient department treatment. The data obtained revealed that the level of 2,3-diphosphoglycerate was considerably elevated, as compared with the norm, before the treatment. After the active treatment and correction of anemic syndrome it was decreased, but remaining above the norm. By the 60th day of the out-patient department treatment the decrease continued and the level of 2,3-diphosphoglycerate approached the norm. PMID- 4036091 TI - [Cytochemical study of lymphocyte nucleoproteins in rheumatoid arthritis patients]. AB - The purpose of the study is to investigate and juxtapose the cytochemical characteristics of ribonucleoproteins (RNP) and deoxyribonucleoproteins (DNP) in the lymphocytes of patients with rheumatoid arthritis (RA), of healthy lymphocytes and lymphocytes blast-transformed by phytohemagglutinins. Significant differences in the staining of lymphocytes for nucleoproteins were established in all 54 patients with RA studied. The unidirectional changes in the morphological form of the staining for RNP and DNP in blast-transformed lymphocytes and lymphocytes in RA is, most likely, in connection with the transition of the latter into active functional state and their participation in the forming of the immune inflammation. No significant difference was established in the dependence on the RA form--sero-positive or sero-negative. Regardless of the negative serological samples in the second form, there were some changes in the lymphocytes--carriers of immune reactions in organism. PMID- 4036093 TI - [Lofgren's syndrome (a description of a case)]. AB - The authors present the modern concepts about the etiology, pathogenesis clinical, X-ray and laboratory characteristics of Lofgren's syndrome in a concise form and then--their own observation on that clinical X-ray variant of sarcoidosis. The diagnosis was objectivized on the base of the data from X-ray findings in lungs and the histological study on the material from the lungs and skin. The pathognomonic significance of the combination of the pulmonary and skin changes are stressed upon in the presence of negative tuberculin tests. A very good result was recorded from the long-term treatment with corticosteroids in combination with vitamins, calcium preparations and rimicide protection. PMID- 4036092 TI - [Electron microscopic study of the myocardium in 2 cases of primary systemic amyloidosis]. AB - The authors describe two cases with primary systemic amyloidosis advancing with the picture of progressing cardiac insufficiency, clinically not distinguished. Electron microscopic study of myocardium was performed. The ultrastructural data indicate that the most likely source for synthesis of amyloid in myocardium, in primary systemic amyloidosis, are the active fibroblasts, established in interstitium. PMID- 4036095 TI - Continuing medical education in Barbados. PMID- 4036094 TI - [Multiple gangrene of the digits in a female patient with liver cirrhosis, diabetes mellitus and cryoglobulinemia]. AB - A case is described with multiple gangrene of the fingers of a female, aged 55, with confirmed cirrhosis of liver and diabetes mellitus. Cryoglobulins were established in the serum. A disturbed immunological balance was present and the family loading with collagenosis raises the problem of genetic moments of the disturbed homeostasis. The existing diabetic microangiopathy, histologically confirmed by biopsy of skin and subcutaneous tissue, brings forward the question of the complex pathogenesis of gangrene. At the end of her stay in the clinic, the patient developed cerebral apoplexy. PMID- 4036096 TI - Thyroid-gonad relationship in bronchial asthma. PMID- 4036097 TI - Blood sugar levels, weights and heights of Tobagonians. PMID- 4036098 TI - Psychological dependency among students in a "cross-roads" culture. PMID- 4036099 TI - Treatment of infra-renal aorto-iliac aneurysms by total exclusion. PMID- 4036100 TI - Segmental dilatation of the colon and the Stilling-Turk-Duane retraction syndrome. PMID- 4036101 TI - Anti-hypertensive drug regimens for black West Indians. PMID- 4036102 TI - Cancer occurrence in the Cayman Islands over the past nine years. PMID- 4036103 TI - Peptic ulcer disease in Barbadian children and adolescents. PMID- 4036104 TI - Female adolescents with Chlamydia. Tomorrow's candidates for in vitro fertilization? PMID- 4036105 TI - Computed tomographic findings in orbital Mucor. PMID- 4036106 TI - Tuberculous peritonitis developing in a case of documented peritoneal carcinomatosis. PMID- 4036107 TI - Granuloma inguinale in a white teenager--a diagnosis easily forgotten, poorly pursued. PMID- 4036108 TI - Postoperative small bowel intussusception. PMID- 4036109 TI - Immunization for measles. PMID- 4036110 TI - A treatment for enuresis. PMID- 4036111 TI - How to help your patients function better. PMID- 4036112 TI - Epidemiologic and clinical factors of Chlamydia trachomatis in black, Hispanic and white female adolescents. AB - Rates of genital infection with Chlamydia trachomatis, Neisseria gonorrhoeae and Trichomonas vaginalis were determined prospectively in 396 sexually active female adolescents from three ethnically different urban teen clinics. The organisms were identified respectively in cultures of specimens from 21%, 7% and 6% of all adolescents; 28%, 16% and 20% of blacks; 23%, 4% and 2% of Hispanics, and 14%, 2% and 1% of whites. C trachomatis was identified in specimens from 27% of pregnant adolescents and from 42% of adolescents who had gonorrhea or trichomoniasis. Of 85 Chlamydia-positive adolescents, 47 (55%) were asymptomatic. Physical findings significantly associated (P <.001) with chlamydial infection were vaginal discharge, cervical inflammation and mucopurulent endocervical discharge. Not significantly associated (P >.05) with Chlamydia were the use of oral contraception or symptoms of lower abdominal pain, vaginal discharge or dysuria. Because in sexually active female adolescents C trachomatis is three times more common than N gonorrhoeae, care givers need to consider routine screening or epidemiologic treatment (or both) for both pathogens. PMID- 4036113 TI - Anaphylactoid reactions to tolmetin after interrupted dosage. AB - Seven patients had anaphylactoid reactions after ingesting tolmetin sodium. In each case the reaction followed readministration of the drug after an interrupted period of at least three days and within 90 minutes of taking a single 400-mg capsule. None of the patients had had prior anaphylaxis and none were judged atopic. Skin tests to an extract of the drug (0.02 mg) were uniformly negative, whereas a higher concentration produced a nonspecific irritant reaction. In vitro tests in one patient for IgE antibodies to tolmetin and for complement activation were negative. PMID- 4036115 TI - Nasopharyngeal carcinoma. PMID- 4036114 TI - Asbestos and gastrointestinal cancer. A review of the literature. AB - Exposure to asbestos is among several factors cited as possible causes of esophageal, gastric and colorectal cancer. More than 45 published studies have presented mortality data on asbestos-exposed workers. For each cohort, we listed the observed and expected rates of deaths from types of gastrointestinal cancer based on the latest published follow-up. Summary standardized mortality ratios (SMRs) were then derived. Finally, we calculated summary SMRs for total gastrointestinal tract cancer for three occupational groups: asbestos factory workers, insulators/shipyard workers and asbestos miners. Statistically significant elevations in summary SMRs were found for esophageal, stomach and total gastrointestinal tract cancer in all asbestos-exposed workers. Esophageal cancer summary SMRs remained significantly elevated when data were reanalyzed to include only those cohorts with death certificate diagnoses for cause of observed deaths. However, summary SMRs were not statistically significant for stomach and total gastrointestinal tract cancer after reanalysis. Summary SMRs by occupational group showed a significant elevation for total gastrointestinal cancer in insulators/shipyard workers. The elevation was not significant after reanalysis. Based on the results after reanalysis, the elevations in summary SMRs for stomach and total gastrointestinal tract cancer are of a magnitude that could result from diagnostic and investigator error. We conclude that more studies are required before stomach and colorectal cancers are documented as asbestos-related diseases. PMID- 4036116 TI - A cystic lesion in a 55-year-old man. PMID- 4036117 TI - Comparison of flow rates for standard and large-bore blood tubing. AB - One of the clinically significant rate-limiting components in even the fastest of intravenous (IV) fluid systems is the tubing connecting the IV catheter to the IV solution container. We evaluated the effect large-bore tubing has on reducing this limitation on fluid flow, measuring gravity and pressurized flow in standard and large-bore tubing alone and when each was connected to an 8 French and 12-,14 and two types of 16-gauge catheters. When combined with an 8 French catheter, large-bore tubing produces a 126% increase in flow under gravity and a 90% increase under pressure. The improvement with the large tubing was less significant as the catheter size decreased. Studies in normovolemic adult volunteers achieved similar results. Large-bore blood tubing and large-bore catheters should be used in all situations where the need for rapid fluid replacement is contemplated. PMID- 4036118 TI - Primary sclerosing cholangitis--an immunologically mediated disease? AB - Primary sclerosing cholangitis (PSC) is an uncommon, chronic disorder characterized by inflammatory fibrosis usually involving the entire biliary tree. The etiology has been unknown, but PSC is closely associated with ulcerative colitis, which coexists in more than two thirds of patients with PSC. In recent studies 3% to 5% of all patients with ulcerative colitis had PSC. We propose that PSC is, at least in part, an immunologically mediated disease; it is closely associated with human leckocyte antigens B8 and DR3, and circulating autoantibodies to colon and portal tract are frequently present. The anticolon antibody cross-reacts with enteric Escherichia coli. The disease may possibly be triggered in susceptible patients with ulcerative colitis by immunization with antigens shared between enteric microorganisms and the biliary system. PMID- 4036119 TI - Drownings of children and youth in a desert state. AB - Despite the fact that New Mexico is a desert state, the drowning rate (4.3) is 40% higher than that nationally (3.0). More than half of those who drown are younger than 25 years, toddlers and adolescents being at greater risk than other age groups. In an epidemiologic study of a six-year period, male drowning victims outnumbered female and American Indian and Hispanic victims outnumbered whites. Other major risk factors were epilepsy, mental retardation and alcohol abuse. In most drownings in the under-25 age group, the victim was involved in recreation near the water or swimming, although many were partially or fully clothed. Most drownings occurred in lakes, ditches or rivers. Because New Mexico is not a water oriented state, public awareness of drowning hazards needs to be increased and more intensive preventive efforts instituted. PMID- 4036120 TI - Evaluating and treating intractable cough. PMID- 4036121 TI - Pseudofractures in patients with low-turnover osteoporosis. PMID- 4036122 TI - Gastrointestinal histoplasmosis in suspected acquired immunodeficiency syndrome. PMID- 4036123 TI - Factitious hematuria and self-induced Candida albicans fungemia. PMID- 4036124 TI - Anticholinergic agents in cicutoxin poisoning. PMID- 4036125 TI - Dysthyroid ophthalmology. PMID- 4036126 TI - Familial hiatal hernia. PMID- 4036127 TI - Orthostatic hypotension. PMID- 4036128 TI - How do doctors discuss do-not-resuscitate orders? AB - Although patient preferences are important in decisions about "do not resuscitate" (DNR) orders, little is known about how physicians discuss these orders with patients. We asked 15 physicians to simulate discussing such orders with a patient. We found a striking variation in whether physicians explicitly asked for patient preferences, how they described cardiopulmonary resuscitation (CPR) and its possible outcomes and whether they made a recommendation to the patient about DNR orders. There was no pattern to the different amounts of information presented about CPR. Physicians gave conflicting reasons for how they individualized discussions with patients. Awareness of such different behaviors may stimulate physicians to examine what they say to patients about this sensitive and important topic and why they say it. PMID- 4036129 TI - Open-heart surgery--an American experience in Shanghai. PMID- 4036130 TI - Demographics and disease prevalence of two new refugee groups in San Francisco. The Ethiopian and Afghan refugees. AB - Of all the Ethiopian (N=110) and Afghan (N=59)refugees seen at the Refugee Screening Clinic at San Francisco General Hospital Medical Center between May 1982 and July 1983, most were young men and more than 80% of each group were unable to speak English. The most frequently noted medical conditions in both groups were pathogenic parasites, dental caries and skin disorders. Most had positive PPD tests, but only a few cases of class A or class B tuberculosis were found. Among the Ethiopians two active cases each of Plasmodium vivax malaria and trachoma were diagnosed. Although a wide range of diseases were seen, most were common rather than exotic. In addition to the need for translators, traditional beliefs and customs must be sensitively considered when providing health care to these groups. PMID- 4036131 TI - Allergy practice in California. Diagnostic and therapeutic methods used by allergists and otolaryngologists. PMID- 4036132 TI - [Psychosomatic problems in patients with acquired heart defects]. PMID- 4036133 TI - [Mezlocillin in abdominal surgery]. PMID- 4036134 TI - [Detection and therapeutic effects in cervical cancer in the light of preventive examinations of women]. PMID- 4036135 TI - [Case of Budd-Chiari syndrome]. PMID- 4036136 TI - [Jejunal lipoma complicated by triple intussusception]. PMID- 4036138 TI - [Polycythemia in a newborn infant]. PMID- 4036137 TI - [Atypical rapid growth of uterine myoma without evidence of malignant transformation in a 52-year-old multipara]. PMID- 4036139 TI - [Paranoid syndrome in Bourneville's disease]. PMID- 4036140 TI - [Lung separations in children]. AB - Problems in diagnosis and treatment of separation of the lung are shown on the basis of 12 cases. Primarily the atypical supply of the separation by an artery out of the general circulation may cause difficulties. A damaging of this artery may cause lethal bleeding especially when the aberrating vessel ascends from the abdominal region through the diaphragm into the thorax. Diagnosis always gives the indication to operation although sometimes only thoracotomy gives a definite diagnosis. Selective arteriography of the abnormal artery may be useful help. Separation of the lung should be taken into consideration if there is a suspect X ray plan of the thorax. The surgeon then may expect technical difficulties and can avoid complications. The prognosis is excellent. PMID- 4036141 TI - [Cystic fibrosis of the pancreas and lung]. AB - Cystic fibrosis is the most common genetic disease. The basic defect is still unknown. The success in the treatment of pulmonary disease and nutrition transposes this pediatric disease into adult medicine. PMID- 4036142 TI - [Risk factors in problem children]. AB - Results of a study on 2000 children an adolescents with behavioural and psychosomatic disorders, who were treated by the department of neuropsychiatry, Kinderspital Linz, are presented. After the formation of a new station for neuropsychiatry in child and adolescent age we constituted a interdisciplinary teamwork for ambulatory and stationary treatment. This team consists of psychologists, educators and specialized staff. All kinds of neuropsychiatric diseases are to treat, the catamnesis include their prenatal risk factors and all disturbances of development. We tried to correlate the preexistent risk factors with actual troubles and found that intervention would have been possible long before the disturbance in child was apparent (5, 3). PMID- 4036143 TI - [Obligation to render meticulous care in sports medicine]. PMID- 4036144 TI - [Energy yield during physical exertion]. AB - Every energy demanding process in the skeletal muscle is associated with the use of adenosinetriphosphate, the essential muscular high-energy phosphate. ATP is rephosphorylated by ADP (= adenosine diphosphate) and this process depends on the type, intensity and duration of the physical exercise. At the beginning of a vigorous physical exercise utilization of intramuscular ATP and phosphocreatine is predominant (= anaerobic-alactacide energy yielding). Then the ATP rephosphorylation based on the conversion of glycogen and glucose to lactate, especially by an exercise duration till 2 min (= anaerobic-alactacide energy yielding). Toward this duration or if the exertion intensity at start has been below 60 to 70% of maximal physical performance, ADP is rephosphorylated during oxidative phosphorylation by the skeletal muscle mitochondria using glycogen, glucose or free fatty acids as energy fuel. Training, age and sex may influence anaerobic and aerobic energy-yielding as well as metabolism and ultrastructure of skeletal muscle. PMID- 4036145 TI - [Relevance of lactate determination in sports medicine]. AB - In the last years increasing attention has been paid to specific changes of muscle metabolism during physical exertion in the diagnosis of physical performance. Lactate resp. lactic acid, being the terminal product of anaerobic glycolysis, has gained a central position in that field of sports medicine. Measuring lactate concentration level in arterialized capillary blood (drawn from the earlobe) one can investigate both the onset of anaerobic-lactic energy production during increasing work load (aerobic-anaerobic transition) and the maximal amount of anaerobic energy formation during short periods of exhausting work. In this way, using suitable work load protocols, the aerobic capacity (endurance capacity) on the one hand and the anaerobic capacity on the other hand can be determined. Therefore the most prominent components of energy production in working muscle and physical performance in general are accessible by measurement of blood lactate concentration level. PMID- 4036146 TI - [The importance of sports medicine field tests as a means of training control in northern endurance sports]. AB - In endurance sports heart frequency at the aerobic threshold (2 mmol/l lactate) is recommended for extensive training and heart rate at the anaerobic threshold (4 mmol/l lactate) for intensive training. Both values could be estimated by means of exercise tests in the laboratory as well as in the field. However for training-recommendations only data estimated on a specific exercise procedure should be used. PMID- 4036147 TI - Anomalies of pulmonary venous return. PMID- 4036148 TI - Coarctation of the aorta: current surgical management. PMID- 4036149 TI - Conduction tissue in congenital heart surgery. PMID- 4036151 TI - Surgical management of double inlet ventricle. PMID- 4036150 TI - Valve replacement in children. PMID- 4036152 TI - Functional assessment after colectomy, mucosal proctectomy, and endorectal ileoanal pull-through. PMID- 4036153 TI - Screening procedures for identifying patients after gastric operations at high risk of developing premalignant histological changes. PMID- 4036154 TI - Gastrointestinal myoelectric activity following abdominal operations in the opossum. PMID- 4036155 TI - Surgical technique for repair of benign stricture of the bile ducts, preserving the papilla of Vater. PMID- 4036156 TI - Prophylactic regimens in colorectal surgery: comparisons between metronidazole used alone or with ampicillin for one or three days. PMID- 4036158 TI - Lesser curve ischemia after proximal gastric vagotomy and splenectomy: conservative management with endoscopical surveillance. PMID- 4036157 TI - Surgical treatment for malignant lesions of the distal part of the esophagus and the esophagogastric junction. PMID- 4036159 TI - International trends in alcohol production and consumption: implications for public health. PMID- 4036160 TI - Recent trends in cardiovascular disease mortality in 27 industrialized countries. PMID- 4036161 TI - Cardiovascular diseases as a cause of death in the island of Mauritius, 1972 1980. PMID- 4036162 TI - Health development in Japan: determinants, implications and perspectives. PMID- 4036163 TI - The World Health Organization's expanded programme on immunization: a global overview. Expanded Programme on Immunization, World Health Organization, Geneva. PMID- 4036164 TI - Induction of rat-hepatic microsomal cytochrome P-450 and aryl hydrocarbon hydroxylase by 1,3-benzodioxole derivatives. AB - Several 1,3-benzodioxoles (BD) and related compounds were studied in relation to their ability to generate metabolite complexes with hepatic cytochrome P-450 following administration in vivo to rats. BD derivatives that formed stable metabolite complexes with cytochrome P-450 were considerably more effective inducers of cytochrome P-450 and aryl hydrocarbon (benzo[alpha]pyrene) hydroxylase (AHH) activity than derivatives that did not form stable complexes. Linear regression analysis showed that AHH activity was well correlated (r = 0.980) with total (i.e. complexed plus uncomplexed) cytochrome P-450 content and was not correlated with levels of uncomplexed cytochrome P-450. Aminopyrine N demethylase (APDM) activity in hepatic microsomes from rats treated with 1,3 benzodioxoles was moderately correlated in a linear relationship with uncomplexed levels of cytochrome P-450 and not with total cytochrome P-450. PMID- 4036165 TI - Selective inhibitory interactions of alkoxymethylenedioxybenzenes towards mono oxygenase activity in rat-hepatic microsomes. AB - A series of eight 4-n-alkoxymethylenedioxybenzene (AMDB) derivatives were evaluated for their inhibitory effects on several mono-oxygenase reactions and their capacity to form metabolite complexes with cytochrome P-450 in vitro in hepatic microsomes from phenobarbital (PB)-and Beta-naphthoflavone (Beta NF) induced rats. Ethoxyresorufin O-deethylase in Beta NF-induced microsomes and aminopyrine N-demethylase in PB-induced microsomes were most susceptible to inhibition by the test compounds. In contrast, aldrin epoxidation and arylhydrocarbon hydroxylase in PB-and Beta NF-induced microsomes, respectively, were not inhibited by derivatives of AMDB. All AMDB derivatives elicited spectral complexes with cytochrome P-450, the characteristics of which were influenced by the microsomes employed and by the length of the AMDB alkoxy side-chain. Derivatives containing short-chain alkoxy substituents (C1 to C3) formed unstable metabolite complexes and generated substantial quantities of carbon monoxide (CO), those with intermediate length alkoxy groups (C4 to C6) generated little CO and rapidly formed intense spectral complexes (large delta A max), and those with the largest alkoxy groups (C7 and C8) formed no CO and elicited complexes of high stability. Quantitative structure-activity analyses showed that the biological data could be described by parabolic equations in II, the hydrophobic constant of the alkoxy substituent, and suggested the importance to AMDB interactions of a lipophilic-binding region at the active centre of the cytochrome P-450. The alkoxy chain length for optimal mono-oxygenase inhibition and complex formation with cytochrome P-450 appeared to be about five or six carbon atoms. The data suggest that the capacity of AMDB compounds to form stable inhibitory complexes with cytochrome P-450 may not always be associated with their ability to inhibit mono-oxygenase activity. PMID- 4036166 TI - Association between progesterone binding and cytochrome P-450 content of hepatic microsomes in the rat treated with cobalt-haem. AB - The effect of cobalt protoporphyrin IX (Co-haem) given to male rats in single subcutaneous doses (25-100 mumol/kg body wt.) was studied. Co-haem decreased cytochrome P-450 content and aminopyrine N-demethylase activity, but increased progesterone content and 3H-progesterone binding in a dose-related manner. The effect of a single dose of 50 mumol/kg body wt. was reversible; cytochrome P-450 and progesterone content, and progesterone binding, returned to the normal level 24-40 d after injection but aminopyrine N-demethylase activity was only partially restored. The converse actions of Co-haem on microsomal progesterone and cytochrome P-450 content showed high correlation. PMID- 4036167 TI - Carpipramine metabolism in the rat, rabbit and dog and in man after oral administration. AB - Carpipramine administered orally is excreted via the urine and faeces in rat, rabbit, dog and man. Many metabolites are formed, including several conjugates in the urine. A total of 20-25 metabolites was detected by t.l.c. and h.p.l.c., 16 of which were isolated and identified. Three metabolic pathways were observed: hydroxylation of the iminodibenzyl ring to a phenol or alcohol without modification of the side-chain, hydroxylation of the terminal piperidine of the 2 piperidinol side-chain, and cyclization and dehydrogenation of the same 2 piperidinol group. PMID- 4036168 TI - Lack of congruence of S-carboxymethyl-L-cysteine sulphoxidation and debrisoquine 4-hydroxylation in a Caucasian population. AB - One-hundred-and-twenty volunteers and three families were investigated for possible association between the sulphoxidation of S-carboxymethyl-L-cysteine and the debrisoquine hydroxylation polymorphism. The observed individual variations in these two metabolic reactions were shown not to be concordant (rs = 0.068) and any heritable factors controlling the major aspects of these phenomena do not co segregate. PMID- 4036169 TI - Carnitine and glucuronic acid conjugates of pivalic acid. AB - The [1-14C]pivaloyloxyethyl ester of methyldopa administered to man and cynomolgus monkeys resulted in the elimination in the urine of 14C-pivalic acid metabolites. Pivaloyl glucuronide and pivaloyl carnitine were identified as the major radioactive urinary metabolites in monkey urine and human urine, respectively. N.m.r. analysis indicated that pivaloyl carnitine had a cyclic structure. Although the role of carnitine is in the transport of fatty acids across mitochondrial membranes, it may also function in the conjugation of carboxylic acid xenobiotics in humans. PMID- 4036170 TI - The metabolism of phenothiazine in the neonatal calf: identification of drug polypeptide conjugates from urine. AB - The presence of a polypeptide conjugate fraction in the urine of young calves after oral dosing with phenothiazine has been confirmed. Four different polypeptide conjugates, containing up to six amino acids attached to phenothiazine or leucophenothiazone via the carboxyl terminal of the chain, have been isolated, characterized and sequenced. In addition, several minor polypeptide conjugates have been observed. The literature pertaining to polypeptide conjugates of drugs has been reviewed and the importance of this metabolic route in neonatal animals discussed. PMID- 4036171 TI - Biotransformation of sultopride in man and several animal species. AB - The biotransformation of sultopride has been investigated in rat, rabbit, dog and man. In man sultopride was metabolically stable, and about 90% of an oral dose was excreted in urine unchanged and 4% as oxo-sultopride. Rat, rabbit and dog metabolized sultopride more extensively and excreted less than 40% of an oral dose of 14C-sultopride in urine. Four similar metabolites were excreted by the three animal species but the relative portions differed. The major radioactive component in rat urine was O-desmethyl sultopride, whereas oxo-sultopride and O desmethyl sultopride were the major urinary metabolites in rabbit. Dog formed N desethyl sultopride and oxo-sultopride as major urinary metabolites. The male rat excreted smaller amounts of unchanged sultopride in urine than did the female rat. The unchanged sultopride excreted in rat urine was increased slightly by repeated administration. PMID- 4036173 TI - Influence of cytochrome P-450 type on the pattern of conjugation of 4 hydroxybiphenyl generated from biphenyl or 4-methoxybiphenyl. AB - The rate of production of 4-hydroxybiphenyl from 4-methoxybiphenyl in hepatocytes isolated from untreated rats was essentially identical to that from biphenyl in hepatocytes isolated from rats pretreated with beta-naphthoflavone at 40 mg/kg. Similar results were obtained using liver microsomes isolated from untreated or treated rats. The selective inhibition of these reactions by metyrapone, alpha naphthoflavone and ethanol demonstrated that different forms of cytochrome P-450 are responsible for O-demethylation of 4-methoxybiphenyl in livers of untreated rats and 4-hydroxylation of biphenyl in livers of pretreated rats. The pattern of conjugation of 4-hydroxybiphenyl generated from biphenyl in hepatocytes isolated from pretreated rats was different from that for 4-hydroxybiphenyl generated from 4-methoxybiphenyl in hepatocytes isolated from untreated rats, there being a 60% decrease in sulphation measured after 60 min incubation with biphenyl. Glucuronidation of 4-hydroxybiphenyl was not affected. The sulphation of 4 hydroxybiphenyl added directly was significantly decreased in hepatocytes isolated from pretreated rats. The initial rate of glucuronidation of 4 hydroxybiphenyl added directly was not altered by the pretreatment, but there was a significant decrease in overall glucuronidation measured over a 60 min incubation. Similar results were obtained using liver slices. beta-Naphthoflavone added directly to liver slices significantly decreased the extent of sulphation of 4-hydroxybiphenyl but did not influence glucuronidation. There was evidence of a late decrease in biphenyl 4-hydroxylase activity in hepatocytes isolated from pretreated rats. It is concluded that the differences observed in the cellular metabolism of biphenyl and 4-methoxybiphenyl can be ascribed to competition between beta-naphthoflavone and/or its metabolites retained within the cells following pretreatment, and biphenyl and/or its metabolites for the pathways common to their metabolism. It is also concluded that the type of cytochrome P 450 involved in the generation of 4-hydroxybiphenyl does not, per se, influence the subsequent pattern of conjugation. PMID- 4036172 TI - The metabolism of 14C-cyclohexylamine in mice and two strains of rat. AB - After administration of 14C-cyclohexylamine (35-500 mg/kg) to male mice and rats, 80% of the dose of 14C was excreted in the urine, mostly within the first 24 h after dosing. In Wistar rats, 7-9% of the 14C in the 0-24 h urine was present as cis-4-aminocyclohexanol, with a similar amount as the corresponding 3-isomers. In the DA rat, only 1-2% of the 14C, and in mouse less than 1% of the 14C was present in the urine as aminocyclohexanols; unchanged cyclohexylamine accounted for about 95% of the activity. The extent of metabolism was not affected by either dose or route of administration. The species differences in metabolism may be implicated in the differences in toxicity during chronic high-dose administration. PMID- 4036174 TI - The interaction of representative members from two classes of antimycotics--the azoles and the allylamines--with cytochromes P-450 in steroidogenic tissues and liver. AB - Spectrophotometric studies with ketoconazole, clotrimazole and miconazole show strong type-II interactions with several cytochromes P-450, particularly (Ks greater than 10(7)M-1; pH7.4; 25 degrees C) with the 11 beta-hydroxylase of adrenal mitochondria, with the 17 alpha/20 lyase of testis microsomes and with some forms of cytochromes P-450 of liver. A tight binding of the azoles also occurs to the reduced cytochromes, giving rise to an impeded CO binding to the haem iron. The binding of the azoles to 11 beta-hydroxylase and 17 alpha/20 lyase is much tighter than the binding of endogenous substrates, and consequently inhibition of steroidogenesis will occur at these sites. The metabolism of xenobiotic substrates by the cytochromes P-450 of liver will also be severely impeded. In contrast, the allylamines naftifine and SF 86-327 are type-I substrates for a small portion of cytochromes P-450 of liver microsomes only and there is no spectral evidence for binding to the cytochromes P-450 involved in steroid biosynthesis. PMID- 4036175 TI - Enhanced killing of penicillin-treated gram-positive cocci by human granulocytes: role of bacterial autolysins, catalase, and granulocyte oxidative pathways. AB - Staphylococci pretreated with subminimal inhibitory concentrations (subMIC) of cell-wall active antibiotics exhibit increased susceptibility to killing by human polymorphonuclear leukocytes (PMNs), even when phagosome information is impaired by the mold metabolite, cytochalasin B. To investigate the role of specific bacterial factors in the process, studies were carried out with organisms lacking catalase (streptococci) or cell-wall autolytic enzymes and compared to findings with Staphylococcus aureus 502A. Neutrophil factors were studied using inhibitors, oxygen radical scavengers, myeloperoxidase (MPO)-deficient PMNs, or PMNs from a patient with chronic granulomatous disease (CGD). Documentation of the enhanced susceptibility of the streptococcal strains to killing by PMNs following subMIC penicillin pretreatment required the use of cytochalasin B. Enhancement of killing occurred independent of the presence or absence of bacterial autolysins or catalase. SubMIC penicillin pretreatment of S. pneumoniae R36A specifically promoted the susceptibility of these organisms to killing by myeloperoxidase (MPO)-mediated mechanisms (enhancement lost using MPO-deficient or azide-treated cells). Factors other than MPO or toxic oxygen products generated by the PMN respiratory burst are responsible for enhanced killing of penicillin-pretreated S. aureus 502A (enhancement preserved using MPO-deficient, azide-treated, or chronic granulomatous disease patient cells). These studies define methods to study the interaction of antimicrobial agents and PMNs in the killing of microorganisms. They also demonstrate that penicillin treatment can change the susceptibility of gram-positive cocci to the action of specific PMN microbicidal mechanisms. The mechanism of the enhancement appears to be bacterial strain-dependent and not predictable by bacterial autolysin or catalase activity. PMID- 4036177 TI - Alleged susceptibility of the elderly to infection. AB - The widely held notion, common in clinical medicine, that the elderly are more susceptible to infection is discussed critically. Implied but unstated in this sentiment is a premise that host defense mechanisms are less effective in the elderly, or that immune surveillance becomes defective with aging. No clear evidence exists to support these concepts; indeed, available information points to a normally functioning immune system in the elderly. An increased incidence of morbidity and mortality resulting from infection in the elderly does exist, however, and it is suggested that this stems from many of the functional and anatomical deficits which accompany the aging process and therefore predispose the elderly to infection. Examples of these degenerative problems are pulmonary hypoventilation, bronchopulmonary aspiration, immobility, and urinary retention. These conditions can predispose the elderly to infection by common extracellular microorganisms that are the normal flora of the mucosal and skin surfaces of the body. More precise information on the nature of injuries caused by these organisms in the elderly and on the causes of the resulting higher mortality rates in the elderly is required before an increased incidence of infection in the elderly can be attributed to an increase in their susceptibility to infection because of defective immune or host defense mechanisms. PMID- 4036176 TI - The effect of low ambient temperature on the febrile responses of rats to semi purified human endogenous pyrogen. AB - The febrile responses of Sprague-Dawley rats to semi-purified human endogenous pyrogen were studied at a thermoneutral ambient temperature (26 degrees C) and in the cold (3 degrees C). It was found that while rats developed typical monophasic febrile responses at thermoneutrality, febrile responses were absent in the cold exposed rats. Experiments were conducted to determine whether this lack of febrile responses in cold-exposed rats was due to an inability of these animals to generate or retain heat in the cold. Thermogenesis and vasoconstriction were stimulated in cold-exposed rats by selectively cooling the hypothalamus, using chronically implanted thermodes. It was shown that, using this stimulus, metabolic rate could be increased by more than 50 percent and body temperature could be driven up at a rate of 5 degrees C/hour in rats exposed to the cold. Therefore, it was concluded that the lack of febrile responses of cold-exposed rats to pyrogen is in no way due to a physical or physiological inability to retain heat. Instead, it appears that in some manner cold exposure suppresses the sensitivity or responsiveness of the rat to pyrogenic stimuli. PMID- 4036178 TI - [Remarks on toxoplasmosis therapy based on indications]. PMID- 4036179 TI - [Social law and the physician-nurse-patient relation in health care in East Germany]. PMID- 4036180 TI - [Significance of the analysis of birth rates for medicine. II: Social public health evaluation of changes in birth rate in East Germany 1968-1982]. PMID- 4036181 TI - [New knowledge and future tasks of research on growth in East Germany. II]. PMID- 4036183 TI - [Experiences of Soviet surgeons in the diagnosis and conservative treatment of acute pancreatitis]. PMID- 4036182 TI - [Survey on current status of home treatment of psoriasis patients with ultraviolet irradiation equipment]. PMID- 4036184 TI - [Indications for urgent operations in lumbar nucleus pulposus prolapse]. PMID- 4036185 TI - [Some practical questions of traditional care in medicine]. PMID- 4036186 TI - [Evaluation of automobile driving fitness in cardiovascular diseases]. PMID- 4036187 TI - [Accident severity--an attempt at a definition]. PMID- 4036188 TI - [Poisoning with detajmium bitartrate (tachmalcor)--a case report]. PMID- 4036189 TI - [Correlation between thrombolytic therapy and liver rupture?]. PMID- 4036190 TI - [Extent of duties and time structure of activities of district physicians]. PMID- 4036191 TI - [Use of the IUPAC style for chemical compounds in medical writing]. PMID- 4036192 TI - [Procedure in suspected iatrogenic damage of questionable civil rights relevance]. PMID- 4036193 TI - [Definition of concepts]. PMID- 4036194 TI - [Effect of the characteristics of a situation on the perception of its duration]. PMID- 4036195 TI - [Use of city planning hygiene parameters in housing construction with special reference to heating systems to be installed]. PMID- 4036196 TI - [Meteorological observations on extraordinary immission situations in the Erfurt region]. PMID- 4036197 TI - [Control of important noxious pests in the construction and reconstruction of residential and community buildings]. PMID- 4036198 TI - [Effects of ethanol on adrenal medulla]. PMID- 4036199 TI - [DNA distribution in transplanted tumors of the rat]. PMID- 4036200 TI - [Internal processing of iodate]. PMID- 4036202 TI - [Inhalation of carbon disulfide--studies of carbon disulfide intake under dynamic doses]. PMID- 4036201 TI - [Epidemiologic studies of the exposure to dimethylformamide]. PMID- 4036203 TI - [Measurement and control of the intensity of endurance training in patient groups]. AB - In 49 male patients at the age 34-62 years (means = 48.8) during the perseverance training in groups of patients the observation of the intensity aspired for was controlled by means of controls of the heart beat frequency with the help of long term ECG and self-controls of the pulse rate by the patients. As a result of the long-term ECG controls could be established that the intensity areas aspired for was reached by the preponderant number of the patients or even transgressed, that the judgment of the self-controls of the pulse rate must be performed very critically and in their valuation a subjective and methodically caused measuring error must be taken into consideration. References were given the consideration of which shall lead to an improved observation of the intensity given during the perseverance training in groups of patients. PMID- 4036204 TI - [Evaluation of the efficacy of concomitant special psychotherapeutic methods by patients in an internal medicine clinic]. AB - Patients of a medical clinic whose complaints are diagnosed above all as functional are suitably at once also treated by the clinical psychologists. For this purpose the authors created an effective combination of methods. It consists of a group and individual therapy and contains rational and emotional, in addition suggestive and behaviour-therapeutic elements which for each patient are united to an individual concept. For the purpose of the control of efficiency in a particular examination was inquired how the various methods have become effective in the individual patients and which were used preferably, respectively. The inquiry is performed at the earliest half a year after the discharge. Out of 149 answers the most important results are represented and conclusions for practice are derived. PMID- 4036205 TI - [Course of heart beat variability following acute alcohol intake]. AB - Blood pressure, heart rate and mean momentary arrhythmia were measured in 16 healthy test persons before and after acute alcohol ingestion. While the blood pressure remained unchanged, heart rate and mean momentary arrhythmia showed significant differences in comparison to the initial value, in which case the clearer change of the mean momentary arrhythmia in relation to the heart rate emphasizes the sensitivity of the parameter. The results are discussed as a sequel of the increase of sympathetic activity of alcohol/acetaldehyde. PMID- 4036206 TI - [Differential diagnosis of the malabsorption syndrome]. AB - The paper reports on a cachectic patient who hitherto was treated as a case of pernicious anaemia. After a 20-year course of the disease a malabsorption syndrome as a result of an atrophic duodenitis was diagnosed. PMID- 4036207 TI - [Behavior of late ventricular potentials in acute experimental myocardial ischemia]. AB - Locally retarded depolarizations of the ischaemic myocardium are regarded as frequent trigger mechanisms of dangerous ventricular arrhythmias. Up to now, however, there are scarcely systematic investigations concerning their concrete developmental conditions in man, since late potentials can be made evident only by means of expensive invasive methods or signal mediation techniques. Therefore, an animal model should be built, which is suitable for the control of new therapy conceptions with antiarrhythmic drugs. The investigations were performed on 22 pigs in whom under insufflation anaesthesia altogether 10 pressure, flow and contractility parameters as well as 6 epicardial ECG signals were continuously recorded. The episodes of ischaemia were caused by LAD occlusions of different duration and intensity. Typical late potentials could be registered in 5 animals who all had survived complete interruptions of the coronary blood flow of longer than 10 min. The mean duration of the late potentials was 20 +/- 9.2 ms, their amplitudes reached from 150 to 600 microV. Also with regard to time and cycle constancy, the delay of the late Q-potential and the morphology they corresponded to the homogeneous phenomenon, known from man. They always could be derived only from electrodes outside the immediate zone of ischaemia. Neither partial occlusions nor complete interruption of the coronary blood flow in intervals shorter than 10 minutes led to the development of a late potential. The animal model used altogether appears very suitable to investigate the medicamentous influencibility of arrhythmogenic areas of the myocardium under direct control of the dynamic behaviour of ventricular late potentials. PMID- 4036208 TI - [Pathophysiological investigations on the function of artificial hearts]. AB - The mode of action of artificial hearts is in a wide range variable and to be adapted to different conditions of the circulatory systems. The direct regulative function of the peripheral circulation is restricted by the rigid ability of artificial hearts bound to motor drive parameters. Their great dependence on pre- and afterload already in normal calves presumes a harmonized functional capacity of the right and left ventricle. As to the situation in potential recipients of artificial hearts with considerably disturbed macro- and microhaemodynamics there are problems for the choice of suitable conditions of motor drive, in order to favour a right-left balance and an adequate volume. The substitution of the natural regulators by suitable sensors and the regulation of the artificial hearts according to haemodynamic controls and pump parameters, respectively, is necessary to achieve a balanced adequate ventricular function. This complex is subject of an intensive research. PMID- 4036209 TI - [Results of long-term conditioning in patients with myocardial infarction during phase III rehabilitation]. AB - The active kinesitherapy is an essential constituent of the whole rehabilitation process of patients with infarction. Despite the decrease due to the physiology of ageing and the progression of the coronary disease the physical functional capacity can be kept relatively constant also over many years. Thus the quality of the patients' lives can be favourably influenced. Whether the life expectancy alone can be improved at long date by the active conditioning, further on remains unclarified. Aimed differentiated medication, psychosocial measures, the consideration of secondary bronchopulmonary diseases and the well-timed selection for the coronary-surgical intervention must be included into the process of complex rehabilitation of patients with myocardial infarction. In these cases diagnostics and therapy of the somatic risk factors must particularly be taken into consideration during the whole process of rehabilitation in order to decrease the progressing of the basic disease. PMID- 4036210 TI - [Long-term therapy with amiodarone in tachyarrhythmias--report on various experiences with special reference to its side effects]. AB - In 23 patients with symptomatic severe supraventricular and ventricular tachyarrhythmias the effectiveness and the side effects of a long-term therapy with the class III antiarrhythmic drug Amiodarone (Cordarone) in a dosage of 100 800 mg/die in monotherapy and combination therapy were investigated. In these cases it proved to be an excellently effecting antiarrhythmic drug in tachycardiac dysrhythmias at atrial and ventricular level with an altogether good tolerance. In 16 patients side effects appeared and above all concerned corneal micro-deposition without any clinical symptoms (10 patients). In 3 patients nuclear-medically insignificant changes of the function of the thyroid gland were found--also without clinical relevance. Three times a photosensitisation was conspicuous, only in one patient the therapy was finished on account of epigastric trouble after three months. Av-blockings of higher degree, particularly with bundle-branch block and severe sinus bradycardias as well as disturbances of the thyroid function are regarded as contraindications without preceding pacemaker implantation. PMID- 4036211 TI - [Incidence and clinical symptomatology of coronary heart disease in acquired valvular defects]. AB - 220 consecutive patients with acquired valvular defects were checked within the preoperative examination by means of heart catheter with regard to significant coronary stenoses. In these cases a relative frequency of typical and atypical angina pectoris troubles of 0.136 and 0.459, respectively, was the result. In contrast to this significant coronary stenoses could relatively infrequently made evident angiographically: 6/220 (= 0.027). In patients with valvular defects angina pectoris cannot be used as the leading symptom of an additionally existing coronary heart disease on account of bad sensitiveness. PMID- 4036212 TI - [Early and late results after conventional mitral valvulotomy]. AB - In comparison to the commissurotomy on the open heart the conventional cardiovalvulotomy even nowadays is a recommendable alternative. It is burdened by an insignificant early lethality (1.8%). After 10 years the calculated survival probability is 87.6%. Using the ultrasound cardiography, the image intensifier radioscopy and in exceptional cases the invasive ventriculography to a higher degree those patients can be comprehended preoperatively, in whom a more intensive calcification of the mitral valves or a shrinking of the subvalvular apparatus is present. In these cases primarily the valvulotomy and a substitute of the valve on the open heart, respectively, is to be aspired to. PMID- 4036213 TI - [Long-term oil therapy and lipid metabolism in peripheral arterial obstructive disease]. PMID- 4036214 TI - [Nuclear magnetic resonance tomography and its significance for internal medicine according to the current state of knowledge. Literature review]. AB - With nuclear magnetic resonance imaging the modern picture-producing techniques were enriched by a further non-invasive method giving tomograms of the interesting region free of overshadowing, which furthermore renders possible insights into certain metabolic processes taking place by means of enzymes containing phosphorus. With the help of a study of literature was elaborated which importance the method might obtain for the specialty of internal medicine according to the present state of knowledge in a greater clinical use to be expected, and which trends of application can be recognized according to the study of literature. PMID- 4036215 TI - [Clinical and functional studies of diabetic cardiopathy]. AB - In 30 diabetics and 30 patients with healthy metabolism who anamnestically, clinically and electrocardiographically did not show any references to a coronary heart disease the systolic time intervals and contractility indices of the carotid pulse curve were determined in lying position as well as under passive and active orthostasis load. Diabetics with a microangiopathy already under conditions of rest showed a tendency to pathological values. Unequivocal deviations were to be registered under conditions of the tilting table, particularly when the values obtained under orthostasis are related to the measuring data in rest. The restricted cardiac regulation breadth of diabetics with microangiopathy is particularly expressed in a compared with the control groups clearly reduced reaction of the presphygmic phase, the time of pressure increase as well as the quotients PEP/LVET, LVET/ICT and PEPstanding/PEPlying. PMID- 4036216 TI - [Changes in noninvasive cardiovascular parameters by inpatient weight reduction]. AB - 36 normotensive obese and 23 hypertensive obese were treated with an isokaloric reduction diet of 800 kcal/a day under clinical conditions over a 4-week span. Blood pressure and cardiac performance were investigated by means of non-invasive techniques such as systolic time intervals (STI) and calculated indices. A significant decrease was established in systolic time intervals such as left ventricular ejection time and total electromechanical systole, systolic and diastolic blood pressure, myocardial oxygen consumption and cardiac output. Heart rate, preejection index and stroke volume were not diminished under dietary treatment. No decrease of all parameters was found in obese normotensives with a weight reduction greater than 5% after dietary treatment. PMID- 4036217 TI - [Generalized primary amyloidosis with massive involvement of the gastrointestinal tract]. AB - On the basis of a generalized primary amyloidosis with massive affection of the gastro-intestinal tract in a 58-year-old male form and localization, methods of pathologo-morphological proof, complications of the gastrointestinal tract as well as therapy of the disease are discussed. PMID- 4036218 TI - [Manifest alcoholic cardiomyopathy]. AB - Report on a 40-year-old male with manifest alcoholic cardiomyopathy during massive chronic misuse of alcohol lasting many years. Discussion of the morphologic findings, clinical symptoms as well as of the results of animal experimental studies concerning this clinical picture. PMID- 4036219 TI - [Significance of cardiovascular research within the scope of the total development of medical sciences in East Germany]. PMID- 4036220 TI - [Comparative studies of contractile heart function using impedance, echo-, radio- and apex cardiography]. AB - 89 patients (31 healthy subjects, 31 hypertensives, and 27 patients with coronary heart disease) were examined simultaneously by means of impedance (ICG)-, ultrasonic (UCG)-, radio (RCG)-, and calib. and diff. apex cardiography (cACG). There were found significant correlations between the ICG-, UCG-, and RCG parameters, all describing the heart function in the auxotonic ejection phase. Whereas there were no significant correlations between the methods mentioned and the cACG. Of all investigated parameters in hypertensives only the quotient A/S of cACG is significantly increased compared with persons with healthy heart and circulation. In patients with coronary heart disease all the parameters of the auxotonic ejection phase are significantly decreased, the isometric contraction time and the quotient A/S are increased. PMID- 4036221 TI - [Bromocriptine treatment of hyperprolactinemia]. AB - In 36 female patients with microprolactinoma was carried out a primary therapy and in 19 patients (10 males, 9 females) with a postoperatively persisting hyperprolactinaemia a secondary therapy with bromocriptine. In close correlation between the PRL-levels and the bromocriptine dose we achieved a normalisation of the hormone levels in the microprolactinomas. A normalisation of the cycle was observed in 80%, a persisting of the galactorrhoea in about 90% and a conception in nearly two thirds of the women. Also in those patients who underwent a secondary therapy in nearly 80% a decrease of the PRL-levels into the normal region developed. In a longterm therapy with bromocriptine a reduction of the dose may become possible, so that controls of the hormone levels are necessary in larger intervals. Most side effects of a bromocriptine treatment are transitory. PMID- 4036222 TI - [The lipoprotein profile of hypertensive patients and its modification by 4 weeks of physical training during spa treatment]. AB - Investigations of the lipoprotein spectre on 47 male patients with hypertension (mean 49.6 years) achieved a higher proportion of vasoaggressive lipoproteins than in 26 male healthy controls. With the exception of the genetically determined and familial forms respectively, we class the hyperlipoproteinaemia and the dyslipoproteinaemia with the acquired metabolic influences for the manifestation and the further development of a hypertension. By general aerobic perseverance training the hypertension as well as the hyperlipoproteinaemia can be positively influenced. PMID- 4036223 TI - [Therapy of tuberculosis and other mycobacterial infections]. AB - At present every case of tuberculosis recognized in time is curable. The antituberculotic remedies have a causal effect, since they achieve a destruction of the germs. Decisive for the success are the observing of the treatment instructions and the cooperation with the patient in a period of 6-9 months. The action mode of the basic pharmaceutic agents, the dynamics of bacterial populations and the newest therapy recommendations are listed in tables. In the case of leprosy we look forward to similar results. Here the chemotherapy must, however, be performed for 2 years and longer. In the Buruli-ulcer (mycobacterial skin ulcer) after additional surgical interventions are still to be recommended. Mycobacterioses caused by other human-pathogenic atypical mycobacteria are also cured by a specific treatment of 1-2 years. In particular cases resection are still necessary. PMID- 4036224 TI - [Hemodynamics and morphologic changes following stroma-free hemoglobin solutions in animal experiments]. AB - Hemodynamics and pathomorphological signs after infusion of a stroma-free hemoglobin solution with defined stroma rest contend were registered in 24 minipigs. The small intravascular persistence and potential toxicity were the disadvantages of the solution. We noted a falling down of the central venous pressure and an ascent of the middle arterial pressure so the total peripheral resistance. PMID- 4036225 TI - [Changes in protein metabolism in cachexia and catabolism]. AB - Cachexia as a consequence of a catabolic state (stress metabolism) and cachexia as a consequence of too small food intake (inanition metabolism) have to be distinguished from each other fundamentally. A typical amino acid distribution in plasma, muscle, and liver can be observed in the protein catabolic patient. The glutamine metabolism seemed to be of special interest in the severe catabolic patient (e. g. sepsis). Glutamine is the amino acid with the biggest part of the free amino acid pool. This glutamine pool is reduced in the protein catabolic patient. A connexion seems to exist between the lower muscle glutamine concentration and the prognosis of the patient. The parenteral nutrition can stimulate the protein synthesis, but not suppress the protein hydrolysis. Perhaps catabolic factors as, for instance, interleucine I take part in that. These stimulate the protein hydrolysis over the prostaglandin metabolism. PMID- 4036226 TI - N tau-methylhistidine: inhibitor of hepatic protein synthesis? AB - Protein synthesis in isolated perfused rat livers has been studied. Aminoacids at physiological rat concentration (U-14C)-Leucine 0.065 muCi/ml and N Tau Methylhistidine His (Tau-Me) were added to the perfusion medium. His (Tau-Me) from 0.01 to 2.0 mM causes a reduction between 40-60% in the rate of secreted proteins, independently of the His (Tau-Me) concentration. PMID- 4036227 TI - [Acute mucosal damage of the stomach of the Wistar rat and its prevention with the drug combination droperidol/atropine--an animal experiment study]. AB - The employment of the alpha receptor blocking Droperidol with and without combination of atropine for prophylaxis of the acute mucosal damage of the stomach was investigated in the experimental animal Wistar rat. The immobilisation stress in the stress roll was chosen as stress model. The animals get an infusion programme by a central venous catheter. The stomachs were searched for macroscopic mucosal changes after an immobilisation period of 6 hours. The results were certained statistically. The acute mucosal damage in the rat stomach could be prevented in 100% (p 0.05) by means of the drug combination Droperidol/atropine (IV). PMID- 4036228 TI - [Determination of the chemical composition of gallstones by roentgen ultrastructural analysis]. AB - The definition of the chemical composition of human gallstones is shown by means of X-ray fine structure analysis. The simple method allowed a prompt distinction in stones poor and rich in cholesterol and of other ingredients. The method needs smallest test quantities (2 mg) in regard for a conservative medicamentous therapy. PMID- 4036229 TI - [Testing of polyurethane as an implant for its biological compatibility]. AB - A simple biological method is described for testing the biological compatibility of plastics without histological investigation. This is the implantation into the anterior chamber of the rabbit eye. The test material is polyurethane soft foam (SYSpur). It can be observed as biologically compatible. This result agreed with expert opinions on toxicity and histocompatibility. PMID- 4036230 TI - [Effect of halothane on polarographic pO2 measurement]. AB - The oxygen level is changed significantly in case of polarographic oxygen measurements in presence of halothane. This fact can cause a false estimation of the measuring result. PMID- 4036231 TI - [Use of vasectomy]. PMID- 4036232 TI - [Fertility of smokers and nonsmokers]. AB - The contradictory findings concerning the influence of smoking on spermatogenesis that have so far been presented in literature were derived from fertility patients in retrospective studies; our data, in contrast, are based on a blind study of 333 voluntary test persons. The data of 95 smokers and 83 non-smokers remained to be evaluated after application of the following exclusive criteria: comparatively high consumption of alcohol, taking of drugs, taking of medicine, radioactive exposure, and genital diseases. Significant differences between the two groups were only found with regard to behavior; smokers revealed a higher rate of divorces, they drank alcohol and took drugs more frequently, and had had the first sexual intercourse at an earlier age than non-smokers. On the other hand, all spermatological parameters as well as the outcome of cytophotometric examination of the spermatozoon DNA showed a close correlation between smokers and non-smokers. Although an individual (toxic?) reaction to tobacco smoking cannot be ruled out, our findings lead to the conclusion that cigarette smoking has no detrimental influence on the spermatogenesis of healthy men between the age of 20 and 40. PMID- 4036233 TI - [How does ketoconazole affect testosterone metabolism?]. AB - Inhibition of the testosterone synthesis caused by ketoconazole was studied in healthy young men. They received the drug for seven days at a dose of 200 mg daily. Neither the blood level of total plasma testosterone nor that of the free fraction showed any alteration during treatment. 24 hours after treatment, however, the response of plasma testosterone to hCG was diminished. These findings indicate a delayed effect of ketoconazole on the synthesis of testosterone, although its blood levels are decreased to nearly zero. The effects of ketoconazole are due to its binding to enzymatic proteins. Thus the link to other proteins binding androgens might be possible. Our experiments demonstrated that ketoconazole may inhibit the binding of testosterone to antibodies in a RIA system as well that to SHBG. PMID- 4036234 TI - [The diagnostic significance of short-time intravenous tests with human chorionic gonadotropin]. AB - The normal response of testosterone synthesis to hCG has a biphasic pattern. After a short peak within four hours, there is a decrease followed by a second peak within 24 to 48 hours. In an endocrine system without other disturbances, the short-term reaction is a good parameter for Leydig cell function. We analyzed the short-term tests of 266 patients. Clinically normal persons (181) showed an increase of testosterone from 8.3 to 10.1 ng/ml after 2 hours. Similar levels were found in patients with varicocele, while men suffering from testicular hypoplasia responded by lower values (6.2 and 7.8 ng/ml). Patients with psychogenic impotence reacted significantly less (9.5 basally and 7.6 ng/ml after 2 h), whereas normal response was observed in patients with impotence due to hypertonus (9.0 to 11.0 ng/ml - n = 7). The comparison of our test results with the outcome of hormonal stimulation of spermatogenesis in oligozoospermia (n = 73) shows that better results are obtained if hCG produces a higher quotient. There have been no side effects of the test observed. In 81 patients, blood was tested at least 4 weeks later for the occurrence of hCG-antibodies; they were not demonstrable in any case. The short-term test is a simple, time-sharing method for testing of Leydig cell function. PMID- 4036235 TI - [Trust-promoting variables in child-adult interaction]. AB - As interpersonal trust is recognized as a central variable in child psychotherapy, and as psychological research has not yet developed strategies to advance interpersonal trust, the question arose by which social behavior variables children's trust is determined in the interaction process between adults and children. After having developed a most concrete definition of trust in terms of social interaction behavior, everyday pedagogical interaction sequences involving adults and children were analyzed in order to identify behavioral elements or patterns of interaction conducive to trust. According to the hypotheses, the behavior classes "positive adult reaction", "adult trusting behavior" and the interaction pattern "positive adult response to child trusting behavior" were found as conducive to interpersonal trust in children. Furthermore the realisation of the pattern "alternation of trusting child behavior and positive adult behavior" for a longer period of interaction was identified as material to the foundation of interpersonal trust. The realisation of that pattern is encouraged by positive and permanent reinforcement of different child reactions by the adult and by the child's readiness to react trustfully to positive adult behavior. PMID- 4036236 TI - [Sense and sense relations in psychopathology]. AB - The pair of concepts "sensible/absurd" should be differentiated from the pair of contrasts "true/false". Whether the relation between a subject and its way of being may be evaluated as sensible can not be decided with regard to the presumedly transindividual standard form characteristics of the method of experience. Sensible or senseless is a statement on a relationship included in a perceived field of action, referring two partners within a common symbolic world of senses to one another, and thus obliging them to a particular conception of reality determining their own and their expected behaviour. PMID- 4036237 TI - [Time and anxiety]. AB - We haven't to speak about "experienced-time", but about the "time-lived". The past is experienced the present time is lived in the moment, the future is anticipated. To the type of man, leaning to schizophrenia, to melancholia, to epilepsy, one of these kinds of time-realisation becomes always specifically overwhelming. For the schizophrenics the anxiety is typical, to be not able to realise his "self", because the anticipation of future is disturbed. The melancholics are anxious, not be able to remain in the orders of the past. The anxiety of the epileptics is, to lose the individual beeing in the "momentaniness" of the present. All kinds of psychoses are in an immediate context with the manner "how the self in his fundament is living and is opening the time". PMID- 4036238 TI - [Development of a questionnaire for problem solving]. AB - Presented is the development of a measuring instrument in order to assess the problem solving ability (PLF). The PLF consists of 5 scales: a) experiencing problems, b) problem denial, c) tendency to solve problems in an unconventional way, d) dealing with the problem and e) tendency to conservative problem solving. Test-theoretical analyses are reported as well as, in greater detail, studies for test validation on various populations. High covariations can be shown especially for personality factors. PMID- 4036239 TI - [Case history and the "unlived life"]. AB - This article shows that case history cannot exclude that widely overlooked element of the past called "unlived life", which causes undoubted effects on the present state and on judgement of the future. Man separates each moment "unlived life" from lived historical reality by renouncing, rejecting, missing and letting slip. Tragedy as well as hope of human life are captured in the dialectic relation of renouncing and missing because man is permanently kept in the suspense, whether the reliefing renounce of today might change to a burdening sick-making missing of tomorrow. Parallels to the communication theory of D. Wyss, and the possibility to get down to the "unlived life" of a patient by using the TAT and the "Wurzburg questionnaire" are shown. PMID- 4036240 TI - [Compulsion in neurosis, psychosis and psychosomatic disease]. AB - Obsessive-compulsive phenomena are ubiquitous. Therefore onesided nosological categorization, e.g. viewing obsessive compulsive phenomena as variants of psychosis, seems inappropriate. After discussing these problems of definition, the clinical presentation and relative importance of obsessive-compulsive phenomena in neurosis, psychosis and psychosomatic disorders will be investigated. It will be shown, that the respective obsessive-compulsive syndromes share in common an auto-protective "function", i.e. obsessive compulsive phenomena can be regarded as a counterregulative attempt of the individual to stabilize unstable structures. That the obsessive-compulsive phenomena tend themselves to have a highly pathological quality, is the reverse of this coping behavior. PMID- 4036241 TI - [Configuration frequency analysis. XXIb. Analysis of type of bivariate curves of hyper- and normotensive patients]. AB - The paper entitled "Configural Frequency Analysis, XXI b. Type analysis of bivariate response curves in hypertensive and normotensive subjects" is concerned with plasma levels of epinephrine and norepinephrine recorded in the course of a mental strain experiment. Plasma level response curves allow to identify univariate and bivariate types of response patterns. "Discriminant" and "association" types of hyper- and normotensives are demonstrated as two alternative ways of interpretation. The types are seen as psycho-endocrinological correlates of psychosomatic induced hypertension. PMID- 4036242 TI - [Follow-up of patients with minor grades of dilated cardiomyopathy]. AB - It is not known whether dilated cardiomyopathy (DCM) with a slight reduction of left ventricular contractions represents an "early form" and is liable to deterioration. 29 patients (mean age 45 +/- 10 years; 66% women) with mild DCM (angiographic ejection fraction between 50 and 60%, mean 56 +/- 3%) were prospectively studied for 4.0 +/- 1.7 years. No patients died. Comparing the beginning of this study (I) with its end (II) the mean clinical class (I 2.0 +/- 0.4, II 2.0 +/- 0.4), cardio-thoracic ratio (I 0.48 +/- 0.05, II 0.47 +/- 0.04), the end-diastolic diameter of the left ventricle (I 52.2 +/- 6.2 mm, II 53.0 +/- 5.2 mm) and fractional shortening in M-Mode echocardiography (I 28.3 +/- 6.8%, II 29.4 +/- 7.1%) remained unchanged. Compared to the angiographic ejection fraction at the start of the study, this parameter was slightly reduced in the final examination by 2-dimensional echocardiography (46 +/- 7%). One patient with definite echocardiographic and clinical deterioration showed from the outset a distinct increase in end-diastolic size of the left ventricle. Four patients with improvement in M-Mode parameters did not fundamentally differ from the rest of the patients. Our results indicate that a slight reduction in contractions rarely deteriorates further, and should thus not always be considered as an early form of DCM. PMID- 4036243 TI - [Follow-up of familial idiopathic dilatation of the right atrium]. AB - In 1979 the diagnosis of idiopathic enlargment of the right atrium had been made in four members of a family, living in the northeastern part of Switzerland. A 5 year follow-up study of these four patients by ECG, chest X-ray, bicycle ergometry and echocardiography showed a variable evolution: One of the two patients with the originally largest atria, showed further massive enlargement of the right atrium, combined with tricuspid insufficiency. One presented unchanged echo findings. In the other two patients with originally smaller atria a discrepancy of the course was also observed: in one right atrial size increased considerably (with appearance of atrial flutter), in the other patient the size of the atrium remained unchanged. In both patients a pericardial effusion occurred. Subjective symptoms and physical working capacity did not change in the four patients. PMID- 4036244 TI - [Prognostic significance of programmed ventricular stimulation in the noninvasive registration of ventricular late potentials in the postinfarct period]. AB - The prognostic significance of programmed ventricular stimulation for assessing ventricular vulnerability and of signal averaging for detection of ventricular late potentials was assessed prospectively in 132 survivors of acute myocardial infarction. The median day of these studies was the 22nd. Programmed ventricular stimulation (PVS) included single and double premature stimuli during sinus rhythm and paced ventricular rhythms at rates of 120, 140, 160 and 180 bpm. The endpoint for stimulation was the induction of 4 or more consecutive echo beats. 59 of 132 patients (45%) had late potentials in their body surface signal averaged ECG. The prevalence was 35% in those with anterior wall infarction and 54% in those with inferior wall infarction (chi 2 = 3.9; p less than 0.05). In 61 patients (46%), 4 or more consecutive echo beats were induced. In 28 of these patients, sustained ventricular tachycardia or fibrillation were initiated. During follow-up (15 +/- 11 months; mean +/- S.D.), there were 4 sudden deaths. Neither PVS nor signal averaging were able to predict these events. Spontaneous symptomatic sustained ventricular tachycardia occurred in a total of 9 patients, all of whom had an abnormal PVS result (sensitivity 100%); 7 of these patients also had late potentials (sensitivity 78%). Stepwise analysis revealed that the combination of late potentials (duration greater than or equal to 40 ms), and of induction of sustained ventricular tachycardia at rates less than 270 bpm had the highest predictive value (50%). In contrast, the prevalence of sustained ventricular tachycardia was as low as 3% in those without late potentials.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4036245 TI - [Analysis of right atrium function in patients with chronic pressure overload of the right ventricle]. AB - Right atrial function was evaluated in 16 patients with and without chronic right ventricular pressure overload. A simultaneous right atrial pressure recording using a catheter-tip-micromanometer and right atrial volume determination using cross-sectional echocardiography were performed. The pressure-volume curve of the right atrium was composed of an a-loop and a v-loop. The ratio of active atrial emptying to right ventricular stroke volume in patients with right ventricular pressure overload was significantly larger than in the control group (36 +/- 6% vs. 23 +/- 5%, p less than 0.04). The right atrial work was also significantly greater in patients with right ventricular pressure overload (6.2 +/- 2.0 mWs) than in normal subjects (4.2 +/- 2.0 mWs, p less than 0.04). The ratio of active atrial emptying to ventricular stroke volume and right atrial work were significantly related in both control group and patients with right ventricular pressure overload (r = 0.83). Right atrial work also showed a significant linear correlation with right atrial work before active atrial emptying (r = 0.92). We conclude that in patients with right ventricular pressure overload the right atrium shows more pronounced active emptying and contributes to better diastolic filling of the right ventricle. PMID- 4036246 TI - [Estimation of pulmonary capillary mean pressure using TM-mode echocardiography]. AB - The feasibility of estimating the mean pulmonary capillary pressure by simultaneous noninvasive recording of the ECG, the aortic and mitral valve echocardiogram was tested in 50 patients with miscellaneous heart lesions. The Q MVC-/AVC-E ratio was measured from the onset of the QRS-complex in the ECG, the closure point of the aortic valve, the early diastolic opening of the anterior mitral valve (E-point) and the systolic closure of the mitral valve leaflets on the echocardiogram (C-point). A linear correlation exists between the mean pulmonary artery wedge pressure and the Q-MVC-/AVC-E ratio (n = 50, r = 0.75, p less than 0.001). The echocardiographic derivate index (Q-MVC-/AVC-E) is useful in assessing an elevated left ventricular filling pressure, but the individual data revealed variation in the predicted relation between Q-MVC-/AVC-E and left ventricular end-diastolic pressure. The Q-MVC-/AVC-E ratio is not a useful parameter in predicting left ventricular end-diastolic pressure in patients suffering from a left ventricular aneurysm or an acute transmural myocardial infarction with extensive regional abnormal wall motion. Many criteria such as mitral valve disease, atrial fibrillation, atrioventricular block and left bundle branch block suggest that the Q-MVC-/AVC-E ratio is of limited clinical value. The left atrial emptying index was measured by using the amplitude of the posterior aortic wall motion occurring in the first third of the passive emptying period.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4036247 TI - [Peripartum cardiomyopathy--a case report]. AB - Peripartum cardiomyopathy (PPCM), a disorder of heart muscle, presents with the onset of cardiac failure in the last month of pregnancy or in the first 5 postpartum months. A patient with foudroyant clinical course is presented. Despite detailed clinical investigations and postmortem examination no aetiological factor was found. Diagnostic and therapeutic possibilities are discussed. PMID- 4036248 TI - [Right atrial thrombus formation following transvenous catheter ablation of the AV conduction system]. AB - A case is reported in which the formation of a right atrial mass was detected by two-dimensional echocardiography 3 weeks after successful transvenous electrical ablation of the atrioventricular junction had been performed. The mass was attached to the atrial septum at the site where the electrode catheter used for the ablation had been located and it exhibited no mobility. It was interpreted as a right atrial thrombus induced by the ablation procedure. Although no pulmonary embolic events have been observed during a 7-month follow-up period, right atrial thrombus formation must be considered as a potentially dangerous complication of transvenous catheter ablation to control supraventricular arrhythmias. PMID- 4036249 TI - [Carcinoma in the elderly]. PMID- 4036250 TI - [Functional age of the cardiovascular system and its assessment by age equivalents]. AB - The method for biological (functional) age assessment of the blood circulation system has been developed from the age equivalent value estimated on the basis of a number of indices reflecting the function of a given system. For mathematical processing discriminant analysis was used. Formulae illustrating the biological (functional) age assessment of the human cardiovascular system are presented. PMID- 4036251 TI - [Aging of lens epithelial cells and their possible effect on lens opacity (senile cataract)]. AB - Proliferation capacity, synthesis of lens-specific proteins, DNA alterations after UV- and X-ray irradiation as well as their repair capacity have been investigated in tissue cultures with isolated lens epithelial cells of different species and different donor ages, respectively. The in-vitro life span of diploid lens epithelial cells is limited. It is correlated positively with the life expectancy and negatively correlated with the donor age of the investigated animals. The capacity to synthesize lens-specific proteins is lost in late cultures of lens epithelial cells. The capacity to repair UV- and X-ray-induced DNA alterations does not change during aging in vitro, however, it decreases to 75% in cultures derived from old donor animals (bovine). Together with the special growth pattern of the organ lens, the in-vitro results are discussed in order to point out a possible mechanism which might contribute to the development of age-dependent lens opacities. The system "lens epithelial cells in vitro" is considered as a well-suited model system to study age-dependent alterations in the organ lens. PMID- 4036253 TI - Toxic factors in shock. PMID- 4036252 TI - The situation of clinical gerontology in Europe. AB - A summary of education in gerontology/geriatrics, hospitals and institutes for the aged and organised courses for the elderly in Europe is presented. The report is based on a questionnaire sent to the members of the Council of the European Clinical Section of the International Association of Gerontology in 1984. PMID- 4036254 TI - [Circadian rhythm of parameters of lipid metabolism]. PMID- 4036255 TI - [Stress proteinuria under various training conditions of athletes]. PMID- 4036256 TI - [A kinetic method for determination of malate dehydrogenase isoenzyme activities in blood plasma and tissue samples]. PMID- 4036257 TI - [Interference of cephalosporins in creatinine determination]. PMID- 4036258 TI - [Elimination of foreign impulses in leukocyte counting with the Picoscale type PS 4]. PMID- 4036259 TI - [Experiences with the clarification of lipemic sera using Fri-dohna 113]. PMID- 4036260 TI - On the quality and magnitude of mechanical stresses in the locomotor system during rapid movements. PMID- 4036261 TI - Linear growth of the tibia in Chinese chinese. PMID- 4036262 TI - Age related tooth size variation in the Lengua Indians of Paraguay. PMID- 4036263 TI - [Functional morphologic mechanisms of lymph transport]. AB - The phenomenon of the lymph flow in the initial lymphatics and lymphangions of collecting vessels has been studied. Special attention was paid to the structural features and functional mechanisms of the lymphatic vascular system as well as the influence of extravascular factors on the lymphatic flow. In this context, a survey of the current knowledge of functional-morphological research in lymphology is given which may lead to a better understanding of a disturbed lymph flow under pathophysiological conditions. PMID- 4036264 TI - [Triple diagnosis]. PMID- 4036265 TI - [Myogeloses, their pathogenesis and their lymph drainage, heat and exercise therapy]. AB - Pathogenetically, myogeloses are nonspecific mesenchymal reactions with slight inflammatory symptoms which frequently arise due to capillary hypoxemia. The exudative muscle connective tissue inhibitions which arise in the form of high protein edema are an absolute indication for specific combination treatment, which mainly consists of the manual lymphatic drainage therapy of our school. The principles and the kinds of treatment in several stages, phases and combinations are explained and described. PMID- 4036266 TI - [Cases from edema consultations]. PMID- 4036267 TI - [Medicolegal findings in historic materials]. PMID- 4036268 TI - Clinical effectiveness of rubella vaccine in a college population. AB - An outbreak of rash-like illness compatible with rubella occurred among the student population of a large university in Los Angeles between November 1, 1981 and January 31, 1982. A case-control study was conducted in order to estimate the effectiveness of rubella vaccine in preventing clinical rubella in this university population. Immunization and disease histories were obtained from parents and physicians for 39 cases and 86 controls. For those students with a clear documentation of immunization history, only one of 16 cases (6%) had evidence of prior rubella immunization, compared with 40 of 56 controls (71%). This yielded an estimated vaccine effectiveness of 97% (95% confidence limits of 82% to 100%). The level of protection observed for students immunized with rubella vaccine in our study population was high and comparable to that reported in other recent studies. This supports the notion that the current large reservoir of young adult susceptibles is primarily attributable to past failures to vaccinate school-age children, rather than vaccine failures. PMID- 4036269 TI - Mass vaccination programme aimed at eradicating measles, mumps and rubella in Sweden: vaccination of schoolchildren. AB - In 1982-83, a unique, two-dose programme of immunization with a combined vaccine against measles, mumps and rubella was initiated in Sweden. The first dose was administered at 18 months and the second at 12 years of age. A vaccination study was carried out on 247 12 year old schoolchildren from four schools situated in two urban and two rural areas. In urban areas, 30% of children were found to be susceptible to rubella and 18% to mumps, compared with 55% susceptible to rubella and 31% to mumps in rural areas. The reverse was found for measles, to which 20% of children lacked immunity in urban areas but only 6% in rural areas. Seroconversion was seen in 82% against measles, in 80% against mumps and in 100% against rubella. Follow-up studies of the timing and the virus dosage are also to be carried out. PMID- 4036270 TI - A Rift Valley fever vaccine trial: 2. Serological response to booster doses with a comparison of intradermal versus subcutaneous injection. AB - A booster dose of a formalin-inactivated, cell culture-propagated Rift Valley fever vaccine (TSI-GSD-200) was administered without significant reactogenicity to 60 volunteers 18 months after they received a three dose primary series. Blood was drawn for serological testing prior to boosting and 10, 49, and 180 days thereafter. Neutralizing antibody response was prompt, being maximum on day 10 and considerably higher than the peak titres obtained on day 42 after the initial series. A marked decline in antibody titres was evident by day 180, as seen for the primary series, but residual titres were substantially higher. The initial series was given in doses of 1.0, 0.5, 0.3, or 0.1 ml and the immune status achieved with these injections was a major determinant of the response to boostering. Secondary responses were highly dependent in magnitude and duration on the prior immune status of the recipient. Evaluation of dose and route of recall inoculation showed 1.0 ml given subcutaneously (SC) to be equivalent to 0.1 ml administered intradermally (ID), though inference should be guarded due to the small sample size. Although 0.1 ml SC dose was inferior to either, it was modestly effective. Intradermal administration of vaccine may be useful for extending the small reserve of vaccine available for use in emergency. PMID- 4036271 TI - Rift Valley fever virus vaccine trial: study of neutralizing antibody response in humans. AB - The serological response to immunization with a formalin inactivated Rift Valley fever (RVF) vaccine was studied in 963 Swedish UN soldiers serving in the Sinai peninsula. Antibody titres were determined with a plaque reduction neutralization test (PRNT). Attempts were made to give all soldiers three injections (1 ml s.c. days 0, 7-10 and 28-30) but 128 soldiers received only two injections. In a group of 51 fully vaccinated individuals, repeated blood samples were collected. Fifty of the vaccinees seroconverted. Serum collected six weeks after the first vaccination revealed the highest antibody titres. The geometric mean titre then decreased rapidly during the following two weeks. Six months after vaccination sera were collected from 433 vaccinees who had received three injections and 379 had antibodies detectable by PRNT (88% PRNT greater than or equal to 10). The corresponding figures one and two years after vaccination were 223 seropositives out of 255 (91% PRNT greater than or equal to 10) and 91 out of 123 (74% PRNT greater than or equal to 10), respectively. Multiple stepwise regression showed that three injections gave a better antibody response than two injections. This analysis also showed that the magnitude of the antibody response was reduced with increasing age. Slight, local and general side effects were reported in 6% of the vaccinees and these reactions occurred in individuals with relatively higher antibody response. PMID- 4036272 TI - Stable oil-in-water emulsions: preparation and use as vaccine vehicles for lipophilic adjuvants. AB - Many of the most potent immunoadjuvants for inclusion in vaccines are extremely hydrophobic surfactants. Lipophilic vehicles are needed as carriers for these water-insoluble adjuvants and to provide the hydrophilic-hydrophobic interfacial surface at which they act. We used emulsifiers comprised of fatty acid esters of polyoxyethylene sorbitan (Tweens) or sorbitan (Spans) to prepare oil-in-water (O/W) emulsions of hexadecane. Emulsion stability could be predicted from a ratio of spectrophotometric absorbance readings at 800 and 400 nm but not from published hydrophilelipophile balance (HLB) values. Emulsions that were stable even after heating or freezing resulted when equal volumes of hexadecane and a 70:30 blend of Tween 80/Span 80(T80/S80) were mixed and then diluted with normal saline solution to the desired hexadecane concentration. This blend of monooleate esters has an HLB value of 11.8. Other Tween-Span formulations were mixed to yield emulsifiers with the same HLB value, but only those that contained either T80 or S80 were effective stabilizers. Instability resulted when both esters were derived from saturated fatty acids. Addition of bovine serum albumin (BSA) antigen to the oil phase of 5% hexadecane emulsions tended to destabilize the emulsions, especially at higher protein concentrations. The surface active adjuvant, hexadecylamine, increased emulsion stability. Highest antibody responses in mice were seen when BSA was added to the internal phase of emulsions, i.e., the oil phase of O/W emulsions and the aqueous phase of W/O (Freund's) emulsions. Addition of the hydrophilic T80 to the aqueous phase of O/W emulsions was detrimental to antibody production. In general, stability, oil concentration, and T80/S80 concentration of emulsions had little effect on IgG levels.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4036273 TI - The rising cost of recruiting interns. PMID- 4036274 TI - Polymyalgia rheumatica with normal sed rate and B-thalassemia: case report. PMID- 4036275 TI - [Elements in the construction of a universal theory of medicine]. PMID- 4036276 TI - [Methodological aspects of the problem of dispensary care]. PMID- 4036277 TI - [The concept of the self-movement of living nature as a methodological basis for the dialectics of biomedical knowledge]. PMID- 4036278 TI - [Logical methodological analysis of the categories of clinical thinking]. PMID- 4036279 TI - [Systems analysis of the state of mental disadaptation as a scientific and methodological basis for studying borderline forms of neuropsychic disorders]. PMID- 4036280 TI - [The medical experiment, its specific nature and essence]. PMID- 4036281 TI - [The problem of the ethos and professional ethics of medical workers in the Polish People's Republic]. PMID- 4036282 TI - [Achievements and tasks in the field of medical ethics in East Germany]. PMID- 4036283 TI - [Health and the environment]. PMID- 4036284 TI - [Epidemiological and clinico-genetic studies of arthropathic and typical forms of psoriasis]. PMID- 4036285 TI - [Quality of dispensarization of patients with dermatoses in relation to the forms of medical services]. PMID- 4036286 TI - [Multiple reticulohistiocytoma successfully treated with prospidin and prednisolone]. PMID- 4036287 TI - [Spontaneous rosette formation by neutrophils in patients with furunculosis]. PMID- 4036288 TI - [Skin manifestations in disseminated intravascular coagulation syndrome]. PMID- 4036289 TI - [Prevalence of psoriatic arthritis among the population]. PMID- 4036290 TI - [Current aspects of the pathogenesis and therapy of granuloma annulare and necrobiosis lipoidica]. PMID- 4036291 TI - [Hepatoerythropoietic porphyria]. PMID- 4036292 TI - [Scleroderma-like form of porphyria cutanea tarda]. PMID- 4036293 TI - [Linear pigmented hairy nevus verrucosus]. PMID- 4036294 TI - [Toxicoderma caused by sweet red pepper]. PMID- 4036295 TI - [Herpes zoster and chickenpox]. PMID- 4036296 TI - [Psychoneurological disorders in patients with severe forms of herpes of the skin and mucous membranes]. PMID- 4036298 TI - [Serum immunoglobulins in patients with chronic candidiasis]. PMID- 4036297 TI - [Treatment of chronic ulcerative-vegetative pyoderma with ericyclin and levamisole]. PMID- 4036299 TI - [Value of mycological tests for the prevention of secondary candidiasis in patients with various endocrine disorders]. PMID- 4036300 TI - [Unusual localization of glabrous skin microsporosis caused by Microsporum canis]. PMID- 4036301 TI - [Effect of photochemotherapy on the melanocyte function of normal skin in short term culture]. PMID- 4036302 TI - [Standard survival medium for performing the Treponema pallidum immobilization reaction in syphilis]. PMID- 4036303 TI - [Results of a discussion of seroresistance in syphilis]. PMID- 4036304 TI - [Humoral and cellular immunity factors in pyodermatitis patients during treatment with hyperimmune antistaphylococcal plasma]. PMID- 4036305 TI - [2 cases of thymoma in patients with the erosive-ulcerative form of lichen ruber planus]. PMID- 4036306 TI - [Congenital pachyonychia]. PMID- 4036307 TI - [Dopegit in the combined treatment of vitiligo patients]. PMID- 4036308 TI - [Acute mercury poisoning from its external use]. PMID- 4036309 TI - [A case of Norwegian scabies]. PMID- 4036310 TI - [Isolation of yeast-like fungi from patients with malignant neoplasms]. PMID- 4036311 TI - [Combined therapy of syphilis patients based on the characteristics of their immunological status]. PMID- 4036312 TI - [Sweet's syndrome (acute febrile neutrophilic dermatosis)]. PMID- 4036313 TI - [Sensitivity of serological reactions in the clinico-serological follow-up and discharge from dispensary observation]. PMID- 4036314 TI - [Errors in the diagnosis of syphilis]. PMID- 4036315 TI - Radioimmunoassay and characterization of woodchuck hepatitis virus core antigen and antibody. AB - Solid-phase radioimmunoassays for woodchuck hepatitis virus core antigen (WHcAg) and antibody (anti-WHc) were developed. WHcAg in woodchuck liver homogenates was characterized by ultracentrifugation in CsCl gradients; both heavy (1.35 g/cm3) and light (1.31 g/cm3) cores were obtained from the liver of an animal during acute WHV infection, which is consistent with observations in hepatitis B virus infection in man. Endpoint titers of anti-WHc were higher in chronic WHV carriers than in animals recovered from acute infections. Both IgM and IgG anti-WHc antibodies were produced by infected woodchucks. A survey of colony woodchucks demonstrated that 88/89 animals having one or more markers of past or ongoing WHV infection were positive for anti-WHc. Thus, serum anti-WHc appears to be a sensitive marker of WHV infection. PMID- 4036316 TI - The quantitative kinetic study of dengue viral antigen by flow cytometry. I. An in vitro study. AB - A system effective in the early diagnosis of Dengue virus infection was developed. The time course kinetics of Dengue virus type 2 (D-2) antigen in vitro were analyzed by Flow Cytometry. Early profiles of D-2 were also studied quantitatively through this method of analysis. The early events of host cell and virus interaction were investigated: attachment, internalization and replication. From these early profiles, the time at which new viral synthesis was detectable differed with each individual trial. These different times were found to be dependent of the phase of the cell cycle. From these results we could detect newly synthesized viral antigen within 10 h after infection. PMID- 4036317 TI - [Electric reactive potentials to events of a positive and negative emotional nature]. AB - The event-related potentials (ERP) in the frontal and posterior associative cortex in the right and left hemispheres were studied in two different outcomes of tennis television game. These outcomes were "win" and "loss" of the ball, the first serving as a model of positive, the second--of negative emotional reactions. The averaging procedure was synchronized with the moment of ball crossing the racket line. The ERP consisted of four waves: P300, N600, P800, N1000. The most characteristic interhemispheric difference for the win was an increase of N600 wave in the left posterior associative cortex and for the loss- a decrease of P800 wave in the right frontal area. Thus the positive and negative emotional reactions have specific spatiotemporal organization and are based on complicated interaction of cortical areas. PMID- 4036318 TI - [Asymmetry of the cerebral hemispheres during comparison of paired visual stimuli]. AB - In conditions of tachistoscopic presentation of visual stimuli, healthy (male and female) right-handed subjects carried out a paired comparison of the stimuli presented unilaterally and in the center of the visual field. In case of recognition of images of words and objects, the number of correct answers and motor reaction time usually did not significantly differ at two interstimuli intervals (1 and 10 s). In comparing images of faces, there also were no differences by the number of reactions, and the reaction time was less at the intervals of 1 s. The left hemisphere dominated at the identification of words and female faces, the right one--at the recognition of male faces. When the right visual field was stimulated images of various classes were recognized more differentially than at the stimulation of the left visual field. The male subjects had more prominent interhemispheric differences than the females. The increase of the interstimuli interval from 1 to 10 s brought to a weakening of the functional interhemispheric asymmetry and decreasing of the differences between the male and female subjects. The obtained data show that in the processes connected with short-time memory, functional interhemispheric asymmetry is basically formed at the initial stages of the information processing. PMID- 4036320 TI - [Role of the mediodorsal nucleus of the thalamus in the function of generalization in the cat]. AB - In chronic experiments on cats contribution of the thalamic mediodorsal nucleus to the organization of the processes of generalization and abstraction was studied by means of alternation method. Electrolytic ablation of the nucleus retarded the learning and impeded the initial stages of formation of the generalization function. Mechanisms of thalamic dementia are discussed. PMID- 4036319 TI - [Activity of 3-neuron cortical microsystems in the cat during conditioned reflex switchover]. AB - Multiunit activity in two projection cortical areas (visual and motor) was studied in cats at conditioned switch-over of defensive and alimentary responses to electrostimulation of the visual pathways. Interneuronal relations of three neuronal cortical microsystems (intra-analyzer connections) and relations between microsystems in the visual and motor cortical areas (inter-analyzers connections) were analysed by the method of crosscorrelation of action potential trains. Similar interneuronal relations were revealed in the motor microsystems and different relations were found in visual ones at elaboration of conditioned switch-over. This apparently indicates the leading role of the cortical projection of the signal stimulus in integration of adaptive behavioural act. On the other hand, the presence of common bonds for alimentary and defensive situations as well as of specific ones for each of them was shown in the distribution of interneuronal connections between the analyzers. The former apparently provide for the realization of the conditioned effector movement of the animal occurring in both situations with participation of the same effector organ (the tongue) The latter determine the character of the specific adaptive reaction. PMID- 4036321 TI - [Functional differentiation of the theta-rhythm of the hippocampus in the cat]. AB - On the model of discriminating alimentary conditioned reflex with spatial separation of the sources of conditioned (CR, light flashes) and unconditioned (feeding trough) stimuli the theta-rhythm of the dorsal hippocampus was evaluated in cats. Two types of the theta-rhythm were observed in the spectrum of the hippocampal electrical activity: low-amplitude, consisting of a slow growing theta-waves (type I) and high-amplitude consisting of rapidly increasing theta waves (type II). The type I theta-rhythm is sensitive to noradrenaline and correlates with behavioural forms directed immediately to the realization of alimentary motivation, while the type II is sensitive to serotonin and correlates with behavioural forms directed to the source of the conditioned stimulus. Enhancement of the type II theta-rhythm takes place during a delay of the expected conditioned stimulus. It is suggested that type I theta-rhythm reflects a level of activity of the brain structures connected with unconditioned mechanisms, with realization of biological motivations, while type II theta rhythm is connected with conditioned reinforcing stimuli; it correlates with various forms of conditioned orienting reflexes and reflects the work of the "nervous model of reinforcing stimulus". PMID- 4036322 TI - [Participation of peptides in processes involved in the development of alimentary motivation in the rabbit]. AB - On the base of behavioural and electrophysiological experiments it was suggested that in rabbits the realization of the dominant feeding motivation into the goal directed behaviour implied at the molecular-genetical level the operative synthesis of gastro-intestinal neuropeptide gastrin or its derivatives. It was supposed that the suppression of genetic information realization in CNS under blocking of peptide synthesis led to impossibility of goal-directed alimentary behaviour organization. This mechanism was found to be specific for alimentary behaviour; any its connection with defensive motivation realization was not observed. PMID- 4036323 TI - [Probability analysis of elements of rat behavior after sudden and signalled interruption of food reinforcement]. AB - Probability analysis was carried out of the appearance of single elements of rats behaviour in the process of extinction of a conditioned alimentary motor reflex. The dynamics of effector behavioural components at a sudden cessation of reinforcement (usual schedule of extinction) was compared with cessation of reinforcement signalled by a previously differentiated signal and with reinforcement cessation preceded by a stimulus initially unknown to the animal. If the reinforcement cessation is signalled by a previously differentiated (negative) stimulus, in response to its action the animals "loose the aim", what is revealed in a rapid complete reduction of all elements of the goal-directed alimentary behaviour. Obviously differentiation signal actualises the memory trace of "nonreinforcement" which was formed in the previous negative experience of the animal; this is revealed in accelerated inhibition of the alimentary motor reflex under extinction. PMID- 4036324 TI - [Effect of deafferentation of the lateral geniculate body on its background activity]. AB - Elimination of reticular inputs to the lateral geniculate body (LGB) by sectioning of one half of the midbrain operculum, did not affect significantly the characteristics of the LGB evoked potential to light stimulus. At the same time LGB response to stimulation of the reticular formation by a single current impulse, though did not disappear completely, but changed greatly: its latency became twice as long, the negative component of the response was no more recorded. In conditions of LGB deafferentation, the characteristics of all rhythms of its electrical activity, besides the alpha-like one, considerably changed. At the same time, exactly this last rhythm underwent the greatest changes on the EEG of the visual cortex. On the basis of the obtained data it is suggested that the reticular formation takes a considerable and multiple part in generation of LGB rhythmic activity and that changes in its characteristics are clearly reflected in the ECoG rhythms formation. Retention of the LGB visual evoked potential and of the response to stimulation of the reticular formation after the section of one half of the midbrain operculum testifies to the presence of several reticular inputs to LGB. PMID- 4036325 TI - [Features of corticofugal effects of the motor area of the cortex on processing of heterogeneous afferentation in the parafascicular complex of the thalamus in the cat]. AB - Evoked potentials to somatic and visual stimuli were recorded in the parafascicular complex (parafascicular nuclei--centrum medianum--Pf--CM) of the thalamus of cats anaesthetized by nembutal. Cooling of the motor cortex was also used. The influence of the motor cortex on processing of the visual and somatic afferent signals at the thalamic level was found to be direct but different by its character. The motor cortex exerted unidirectional facilitatory modulatory action of a tonic type on the processing of visual afferentation and general facilitatory influence against the background of which particular excitatory and inhibitory effects were seen which it exerted on the processing of somatic signals. Episodically the motor cortex completely controlled the afferent inputs activated by somatic impulses. The motor cortical area non-equally influenced afferentation of the same modality forming the different components of the evoked potentials in Pf--CM. On the base of our present and earlier obtained data an idea has been formed of existence of a general principle of differentiated influences of polysensory areas on heterogeneous afferentation on nonspecific and association thalamic nuclei, and of realization of these influences through separation of functionally isolated subsystems in descending pathways. Each of the subsystems by closing separate thalamo-cortical circuits might transmit signals of a single modality. PMID- 4036326 TI - [Formation of plastic connections of the visual system during ontogenesis of the rabbit]. AB - Analysis of evoked potentials and unit activity in the visual cortical projection area of rabbits revealed a definite succession of forming of interneuronal connections in ontogeny. In early postnatal period, the neuronal reactions were characterized by stable responses with one excitatory phase corresponding to initially negative surface evoked potential. Similarity of reactions of neurones situated in the same vertical column was observed and explained by functioning of a system of rigid connections of the thalamic relay nuclei afferents with cortical pyramidal neurones. Beginning from the third week of postnatal life of rabbits the neuronal reactions assumed a distinctly expressed phasic character, and variability of responses was seen along the vertical line. The changes revealed correlated with formation of a system of interneurones providing a possibility of plastic neuronal interaction. A study of the influence of preliminary cortical stimulation of the associative areas showed that intercentral cooperation mediated by cortical interneurones providing a systemic analysis of visual information began to form from the third week of postnatal life and reached the definitive level at later stages of development. PMID- 4036327 TI - [Callosal neurons: monosynaptic connection between them and their descending projections]. AB - Antidromic and monosynaptic unit responses to the stimulation of the corpus callosum and the symmetrical cortical area as well as antidromic responses to pyramidal tract and thalamic nuclei stimulation were recorded in the sensorimotor cortex of unanaesthetized rabbits. Out of 182 callosal neurones 13 exhibited transcallosal monosynaptic responses. 8 out of 56 callosal units responded antidromically to pyramidal tract or thalamic stimulation. Thus callosal neurones may be monosynaptically excited by callosal units via the corpus callosum and by the pyramidal tract units. It was also found that a pyramidal tract neurone may send a collateral through the corpus callosum and at the same time have a transcallosal monosynaptic input. The role of monosynaptic transcallosal excitation of callosal neurones is discussed. PMID- 4036328 TI - [2 types of neurons differing in their plastic properties: study of ionic mechanisms]. AB - Plasticity ionic mechanisms of 2 types of neurones identified in the brain of snail Helix pomatia: habituating and non-habituating to rhythmic intracellular stimulation by DC pulses were studied. It has been shown that the development of habituation is due to entering of Ca2+ into the cell and by its activation of Ca dependent K-conductivity of the membrane, leading to hyperpolarization, decrease of input resistance and elimination of spike response to stimulation. Depression of Ca-dependent K-conductivity by quinine totally blocks the ability of the neurons to habituate to stimulation. The data obtained on non-habituating neurons testify that their non-habituation to intracellular stimulation results from their absence or weak manifestation of Ca-dependent K-conductivity in their membrane. Ca2+ entering non-habituating cells during electrical stimulation may have depolarizing and facilitating effects. PMID- 4036329 TI - ["Fast" and "slow" habituation of auditory evoked potentials in the vertex area in response to repeated presentation of a stimulus]. PMID- 4036330 TI - [Participation of the amygdaloid complex in modulating electrocutaneous responses during extinction of the orientation reaction in the cat]. PMID- 4036331 TI - [Parity of the cerebral hemispheres in the mechanism of recovery of disordered movements after unilateral damage to the motor zone in the cat]. PMID- 4036332 TI - [Effect of shortening the interval between delayed reactions on short-term memory in the rat]. PMID- 4036333 TI - [Reproductive function in rats with different types of higher nervous activity during stress induced by electric stimulation]. PMID- 4036334 TI - [Active avoidance in mice with Robertsonian chromosome translocations]. PMID- 4036335 TI - [Automatic device for studying alimentary motor conditioned reflexes in small laboratory animals]. PMID- 4036336 TI - [Quantitative analysis of auto-oxidation products of cholesterol in food of animal origin]. AB - After extraction with methylene chloride, isolation of the unsaponifiable lipid fraction and enrichment by two-step column chromatography, the oxycholesterols were gas chromatographically separated in the form of their trimethylsilyl ethers on a thin film capillary and identified by mass spectrometry. The three major products of cholesterol autoxidation were cholest-5-en-3 beta, 7 alpha-diol(I) its 7 beta-epimer(II) and 5,6-epoxy-cholestan-3 beta-ol(III). In addition, traces of cholestan-3 beta, 5 alpha, 6 beta-triol and cholest-5-en-3 beta,25-diol were detected in some samples. Quantitative analysis was performed with cholest-5-en-3 beta,19-diol as internal standard. The highest concentrations of I-III were found in spray dried egg powders (total amount 15-60 micrograms/g). Parmesan cheese, butter oil and sausages contained significantly lower levels of I-III (total amount 0.1-2.6 micrograms/g). The concentrations of I-III increased strongly when butter oil and beef tallow were heated at 170 degrees C in the presence of air for a longer period. PMID- 4036337 TI - [Acids in coffee. XI. The proportion of individual acids in the total titratable acid]. AB - 22 acids in ground roast coffees and instant coffees were determined by GLC of their silyl derivatives (after preseparation by gel electrophoresis) or isotachophoresis. The contribution to the total acidity (which was estimated by titration to pH 8 after cation exchange of the coffee solutions) was calculated for each individual acid. The mentioned acids contribute with 67% (roast coffee) and 72% (instant coffee) to the total acidity. In the first place citric acid (12.2% in roast coffee/10.7% in instant coffee), acetic acid (11.2%/8.8%) and the high molecular weight acids (8%/9%) contribute to the total acidity. Also to be mentioned are the shares of chlorogenic acids (9%/4.8%), formic acid (5.3%/4.6%), quinic acid (4.7%/5.9%), malic acid (3.9%/3%) and phosphoric acid (2.5%/5.2%). A notable difference in the contribution to total acidity between roast and instant coffee was found for phosphoric acid and pyrrolidonecarboxylic acid (0.7%/1.9%). It can be concluded that those two acids are formed or released from e.g. their esters in higher amounts than other acids during the production of instant coffee. PMID- 4036338 TI - [High performance liquid chromatographic determination of organic acids, sugars, glycerin and alcohol in wine on a cation exchange resin]. AB - The main constituents of wine (ethanol, glycerol, glucose, fructose, tartrate, malate, lactate, succinate, acetate and citrate) were separated by HPLC in one run and determined quantitatively in a time of 25 min. The stationary phase was the cation exchange resin HPX 87H and the mobile phase was dilute sulfuric acid. The results of the HPLC analysis of several wines are presented. Good agreement is observed with the results obtained by conventional methods. PMID- 4036339 TI - Rapid thin-layer chromatographic screening method for the detection of five sulfonamides in swine tissues: collaborative study. AB - A rapid thin-layer chromatographic screening method for five sulfonamides in swine tissues was studied collaboratively in nine Dutch laboratories. All collaborators were sent fifteen swine muscle and fifteen swine kidney samples. These were obtained from treated swine or from swine tissues spiked with sulfonamides at levels ranging from 0 to 0.4 mg/kg. The study indicates that the method is suitable for the screening of animal tissues for these sulfonamides. False scores occasionally occur at the lowest levels. PMID- 4036340 TI - [Implementation of prevention: imperatives of multiple collaboration and action within the community]. PMID- 4036341 TI - [From prevention to health promotion]. AB - There has been much talk about prevention in recent years in industrialized countries, especially in view of the problems care systems encounter. Often however, one refers particularly to secondary prevention, which is in fact the first step of a treatment process. It is essential to take into account the risk factors acting upstream, which medical professions have not done enough in the past. One has not considered enough either the inequalities which are still a frequent occurrence in our populations, and the multiples traumas of various sorts which present living environments inflict on individuals. Sometimes, excessive emphasis has been put on "negative" aspects (blame, social control) of prevention. These facts have lead to the elaboration of the concept of health promotion (and positive health), which implies an action on the environment, as well as the growth of everyone's ability to manage this environment and his own development. In this framework the creation of an adequate community oriented information system is very important; sharing of knowledge, skills and attitudes is indispensable. Health promotion, including the just mentioned sharing, includes certain risks. One may even wonder what a life fully focussed on health, where any transgression will be linked to guilt feelings, would really be. What would be its ideological underpinnings? These problems are by no means neutral, they reflect the consistencies as well as the contradictions of our society. This is one reason why research is much needed on these subjects in the future. PMID- 4036343 TI - [Health and disease: concepts, values amd practices in everyday life]. AB - The article deals with the health and illness concepts and values of different social groups. The results are based on a survey of 443 persons, 20 to 65 years old, living in the German or French speaking part of Switzerland. The health and illness concepts and values are analyzed and their impact on the everyday health and illness practices is shown. Based on these results some conclusions concerning health education programs are drawn. PMID- 4036342 TI - Low birth weight and preterm birth: the emerging importance of prevention. AB - This article on LBW and preterm birth was prepared for this issue, "Interdisciplinary Strategies for Prevention", recognizing its US focus in relation to a European audience. Although the pregnancy and infant health magnitude of the problem is greater in North America, its multifactorial nature and serious impacts are experienced worldwide. Emphasis has been placed on its high costs vis-a-vis neonatal mortality, childhood morbidity, and medical care expenditures for tertiary level management. Three preventive health care strategies, linked to an attractive sociobehavioral model, are presented. The model displays multiple risk factors and their interrelationships, including the pathophysiologic events that lead to LBW and preterm birth. Acknowledging the primacy of basic societal level changes, the strategies nonetheless are based in the health care services. They call for interdisciplinary interventions as a part of preconceptual and prenatal health care. Such approaches as reduction of stress and other risk behaviors, improved nutrition, family planning and social services as well as strengthening family and community support systems are suggested. In addition a secondary prevention strategy dependent on identification of pregnant women at high risk of LBW and preterm birth is described. Early recognition by patients and providers of signs of uterine irritability may enable prevention of preterm birth by prompt treatment with tocolytic agents. Evidence relevant to the effectiveness of the preconceptual and prenatal care interventions, insofar as it is available, is cited. PMID- 4036344 TI - [Interdisciplinary advances in the area of prevention]. AB - In the field of prevention, there is a need for increased interdisciplinarity. This notion requires integration of scientific conceptions and methodology. But the social monopoly given to curative medicine and extended to preventive medicine doesn't make such an interdisciplinary opening easy. PMID- 4036345 TI - [Active teaching of health: conceptualization of intervention programs for children and adults]. AB - The programs described are based on a participant-centered pedagogical method, with the objective to make the individual autonomous and responsible for the management of his health. The underlying theory is interactionist and socio constructivist. The person is continuously changing. Through exchanges with his socio-relational environment, he evolves toward affective, cognitive and social maturity, provided that he be actively involved in the process. Our educational contexts are activities in which each one is involved and on which he later reflects. In such group situations, the individual expresses himself, interacts, confronts others, which allows him to clarify, readjust and enlarge his system of thought. He also is able to better analyze and master his behavior, and to react more adequately in front of conflict situations. Each one elaborates his own solutions. Such health education programs aim thus at the development of optimal capabilities in the person, in order to promote his physical, psychic and social wellbeing. PMID- 4036346 TI - [Health education in St. Gall schools: experiences from a 6-year project]. AB - In 1982 a general concept for comprehensive health education in schools worked out by an interdisciplinary project team was introduced by the Educational Council. Health education is postulated primarily as an educational principle, but in addition to this general principle 13 distinctive content areas are put forward. In a second phase special project teams for each type of school had to transform the general concept into their own specific needs for the age groups concerned. The most important experiences from this phase can be summarized as follows: Concepts for health education in schools have to be worked out by interdisciplinary teams coordinated by an expert belonging to the educational (not the medical) system. Planning and introduction of health education has to be accompanied by changes in attitudes on all levels; the need for time must therefore not be underestimated. The project team has to discuss its results repeatedly with local educational authorities and teachers in order to ensure practicability and acceptance of its proposals. The cross-curricular nature of health education has to be stressed and to be demonstrated by working out and applying practicable models. Teachers have to be carefully prepared for their task not only by providing them with adequate material but above all by including health education as a priority in the training period as well as in postgraduate courses. PMID- 4036347 TI - [Introduction of health education in Vaud schools]. AB - The traditional activities of screening are the prerogative of the school health professionals. Nonetheless health education should be approached in an interdisciplinary fashion and involve the form teachers as well as the specialized area teachers. This article describes a program of health education which is about to be organized in the canton of Vaud. This programs plans for the introduction of health education in the general curriculum and not limit it to a specific period or course. The themes are graded to the age of the pupils. Documents are being worked out by an ad hoc committee and will be available to teachers who desire them. The article also reviews the present activities in health education both at primary and secondary levels and reports on a number of experiences to make teachers aware of health problems. The article concludes on the advantages and difficulties that are linked, on the one hand, to the introduction of education for health in the basic curriculum and, on the other hand, to the use of teachers as promoters of health awareness. PMID- 4036348 TI - [Responding to health needs of apprentices and secondary-school students: current programs in 2 Swiss cantons]. AB - To meet the health needs of adolescents 16 to 19, two Swiss cantons have largely modified their school health systems: this paper describes two programs located in the French speaking part of Switzerland that include both screening and educational activities. These activities are run on an collective and individual basis by specially trained nurses and physicians. Three conditions appear essential for the effectiveness of such programs: priorities should be derived from the needs as expressed by the adolescents themselves. The system should be able to adapt constantly to new problems as soon as they are detected. All activities should be carefully evaluated. PMID- 4036349 TI - [School counselors: from the prevention of drug abuse to a larger role]. AB - Since 1977, a programme has been launched in the Canton of Vaud (pop. 530,000), Switzerland, for the training and use of teachers as mediators in the school setting at various levels, to help tackling problems related to the use of drugs and other risk situations. They follow and in service training (14 afternoons) and are granted, from their working time, about two hours per week to dedicate to this function. Their main role is to be available for reference and empathic listening to children and teacher colleagues, as well as to headmasters, parents, etc. Experience has shown that, in general, mediators are consulted more often for unspecific risk situations, such as difficulties at school and in the family, or "blues". A survey among 51 mediators in function was carried out in 1984 by interviews. It showed a general satisfaction of the ombudsmen with their role. At this time, the student population each deals with is around 600 children. Most of them say they have seen 10 to 20 new cases a year, and follow them up for two weeks to one year usually. Their relationships with various concerned partners are good. They have developed both case work type activities and health educational ones (but there is no systematic drug related information). Some other Swiss cantons and European countries have embarked on similar programs. Such mediators appear to make a useful contribution, complementary to efforts by other interested professionals and institutions. PMID- 4036350 TI - [Breast feeding: the natural means of health promotion]. AB - Breast-feeding has long been accepted as the best way of feeding young children. Promotion of breast-feeding in hospitals has increased the proportion of women beginning to breast feed. The maintenance of lactation however needs other support, which can be provided by self help groups. "La Leche Liga"'s activity centers around this problem. Breastfeeding circles take place in Switzerland too and provide an opportunity for sharing experience and learning to solve everyday problems. PMID- 4036351 TI - [Women and health]. AB - The author, active within a self help group in Neuchatel, Switzerland, describes the reasons for the emergence, first in the U.S.A., then in other countries, of the women's health movement and gives indications on the present situation in Switzerland. In the major cities groups exist or get presently organized. There is a great need for collegial information among women, for more time being dedicated to deal with physical, psychical and social aspects of health, and for fostering autonomy of the women in respect to their own body and care, including self examinations. Unfortunately, up to the present time, the medical profession has shown little interest in such endeavours, and plea is made for a more active participation on its part in the future. PMID- 4036352 TI - [Attitudes and practices of Vaud women concerning the self examination of breasts]. AB - A survey by personal interviews on this subject was carried out in 1984 with a representative sample of 499 women living in the Canton of Vaud. The response rate was 76.6%. Among the respondents, 61.3% practice BSE, but only 27% do so regularly. A complementary inquiry of a group of women who refused the interviews shows a lower practice rate. Women aged 40-49 years, who have benefited more than other groups from related information through their physicians, are those who do BSE most. Our results indicate that such personalized information from a doctor is strongly and positively associated with BSE practice (p less than .001), when compared with "extra-medical" information (mainly from the mass media). There are some negative reactions (fear, reluctance) when the question of BSE is taken up, but they are not major ones and do not influence the interest of the majority of the women (63.3%) in wanting to be better informed on the subject. PMID- 4036353 TI - [Alcoholism and society: secondary and tertiary prevention by directly concerned persons]. AB - Alcohol (especially wine) production and consumption is very much ingrained in the culture and behaviors in Switzerland, especially in the French speaking part. This makes the fate of people with an alcohol problem particularly difficult, as they have to face their addiction, and an attitude of society which is very tolerant for drinking but rather hostile to them. Giving up alcohol means tremendous loss for the drinker, in various ways. With objectives of secondary and especially tertiary prevention, a private association was created in the 1960's, offering to alcoholics opportunities for meeting, discussing their problems, playing. A country house is used for holding retreats. And a home, l'Esterelle, was opened in Vevey in 1966, to house abstinent alcoholics during the rehabilitation phase. Leadership role in these endeavours are assumed by former drinkers. PMID- 4036354 TI - [Cardiovascular prevention in the community: the plurisectorial program of the canton of Tessin]. AB - It describes the primary prevention of cardiovascular diseases carried out in Tessin (Italian-speaking Switzerland). Every single action is addressed to the entire population, actively involving professional associations (doctors, pharmacists, nurses, shop-keepers, etc.) and making use in particular of the collaboration of the mass-media (daily press, radio, television). The described actions concern the struggle against the cardiovascular risk factors through the daily diffusion of tv advertisements, free measurement of arterial pressure, and the possibility of disposing in the majority of regional restaurants of a "Health menu" with a low content of saturated fats and cholesterol. In 1984 every citizen of Tessin has been reached by an average of 24 "preventive messages". PMID- 4036355 TI - [Interdisciplinary strategies in prevention: contribution of nursing practitioners]. AB - This article gives an overview of concepts basic to the notion of prevention as it is understood in nursing today. Human being, disease and health are defined. Different examples of the possible role of nurses in primary, secondary and tertiary prevention are proposed. PMID- 4036356 TI - [Preventive action potential of the primary care physician]. AB - Until now, general practitioners have not integrated prevention as an important component of their work. There is a need to sensitize them to a preventive outlook. The family physician is in a privileged position for such activity, as he maintains a lasting relationship with his patients and knows their environment. He has a pedagogical role, to be accepted and fulfilled, especially in providing the necessary reference and support for the patient to envisage a behavior change. Examples are given of practical situations where such a role is important: overweight, smoking, gynecological screening and a community-wide health education campaign. The author proposes also a self evaluation questionnaire, which practitioners or sickness funds could periodically hand out. PMID- 4036357 TI - [Teaching social and preventive medicine to pharmacy students]. AB - The new Swiss reglementation for the final examination of students in pharmaceutics make social and preventive medicine a mandatory part of the curriculum. The number of hours attributed to the new subject differ markedly between the various schools of pharmacy. They are influenced by the attitude of the institutes and faculties (schools), professional societies but also by the students involved. The experiences of the first year are briefly discussed. Most important is to use the opportunity to improve the collaboration between the different partners in health care. PMID- 4036358 TI - [Role of the sanitary engineer in public health]. AB - This role is exemplified through four cases: the Zermatt typhoid epidemics of 1963, a sanitary survey in Ouagadougou, the bioaccumulation of pollutants in the burbots of Swiss waters and the damages of earthwork in developing countries (roads and dams). The dynamic feature of the concept of "environmental health" is underlined and justifies the inclusion of public health subjects in the training curricula of sanitary engineers. PMID- 4036359 TI - [The law, a possible factor in the promotion of preventive medicine?]. AB - The author observes first the uneven or even contradictory character of existing Swiss law, aggravated by a lack of coordination in terms of its application. He proposes several examples, though noting that the new Federal law on protection of the environment, for which a comprehensive approach has been adopted, might mark a new trend. In a second part, he describes the importance, in the field of prevention, of general constitutional principles the legislator has to take into account, above all in cases of envisaged limitations of fundamental rights. He proposes some legal guidelines which could influence the evolution of health law even in the absence of a direct restriction of individual freedom. An interdisciplinary approach is a necessary condition, especially a close collaboration between physician and lawyer. PMID- 4036360 TI - [Prevention in health and environmental policy]. AB - The article intends to show how important prevention is; not only in the politics of public health, but also in those of environmental protection. A few examples picked out of different fields make it evident that measures provided for environmental protection are at the same time useful to human health. One of the main points is the interpretation of the principle of prevention being one of the most eminent principles mentioned in the federal law on environmental protection, which was put into force on 1st January 1985. Particular importance is to be attributed to the environmental impact assessment as an instrument of prevention. A further main point shows the difficulties and limits that exist when due consideration to the principle of prevention is to be procured. In order to surmount these obstacles, information and enlightenment as well as motivation of each individual citizen are highly important. PMID- 4036362 TI - [1985 scientific meeting, Lausanne]. PMID- 4036361 TI - [Interdisciplinary prevention--a critical analysis of the situation]. AB - We witness a general trend towards increasing specialization and particularism. In Switzerland, this is determined in part by historical and political factors. This trend influences especially the fields of biomedical research, education, the functioning of the health system and the protection of the environment. Preventive medicine is confronted with several obstacles. It certainly is not simple to implement interdisciplinary strategies for prevention and health promotion. It is urgent to make additional resources available, through the creation of a Prevention Fund. Integration and interdisciplinarity are to be promoted in pre and postgraduate training, in research and in the administrations. For the Swiss Society for Social and Preventive Medicine, a consequence is that collaboration has to be strengthened with societies and organisations, medical or not, which have similar purposes. PMID- 4036363 TI - Can modern therapy influence the prognosis of brain injuries in childhood? AB - A standard therapy and the outcome following severe head injury in 51 children are presented. The Glasgow-Coma-Scale was used for classification. Initial therapy included intubation, hyperventilation, ICP monitoring, and barbiturate coma. 14 children had a normal ICP recording, 13 showed moderate (-35 mmHg) ICP elevations, and 23 had recurrent ICP elevations above 35 mmHg. Only one patient survived in a vegetative state. Overall mortality was 21%. All but one of the survivors were controlled one year after the accident. School performance, social integration and the Glasgow-Outcome-Scale were controlled for judging the results. 82% of the surviving children were able to visit a normal school. PMID- 4036364 TI - [Objectivization of psychosocial characteristics in chronic physical deformities. Example: Funnel chest--results of an integrative diagnosis]. AB - In a thorough investigation of 164 characteristics (sequelae) in 41 patients with funnel chest, the fundamentals of a method for "integrating diagnosis" are presented. The symptoms "funnel chest" can be of varied significance, according to the degree of deformity, ranging from a severe handicap to a cosmetic fault. This paper suggests a possible way of objectivating the symptoms, which are often only subjective or only indirectly correlated with the basic illness. Such (psychosocial) stress increases with increasing age, or rather with increasing self-reflection. In these patients, one finds, among other symptoms, reduced capacity for exertion, inhibition of autonomous tendencies, poor estimation of their appearance, subjective feelings of stigma, exaggerated suggestibility, orientation towards failure, fear, and specific shame reactions. The formation of these reactions has a concrete effect on all essential aspects of the patient's way of life. It is recommended that the term "cosmetic indication" be no longer used in diagnosis, and that specific psychotherapeutic measures, as well as operative correction, should as a rule be carried out. PMID- 4036365 TI - Soft-tissue sarcomas in childhood. A study of 262 cases including 169 cases of rhabdomyosarcoma. AB - Although numerous investigations of soft-tissue sarcomas of childhood have been done, there are still many unsolved problems in the diagnosis, histogenesis, and biological behaviour of such tumours. In the present study, the soft-tissue sarcomas collected at the Paediatric Tumour Registry in Kiel were investigated. There was a total of 262 cases, including 169 (64.5%) in which a definite diagnosis of rhabdomyosarcoma had been made. An analysis of the age distribution showed that rhabdomyosarcoma is more than three times as frequent as non rhabdomyosarcomatous soft-tissue tumours in the first quinquennium. Rhabdomyosarcoma exhibited male predominance (male-to-female ratio 1.45:1), whereas non-rhabdomyosarcomatous tumours showed an approximately equal sex distribution. Among the cases of rhabdomyosarcoma, the embryonal type clearly predominated (approx. 70%); the alveolar type was less common (approx. 20%). Correlation of histology with prognosis revealed that even tumours showing tiny foci with an alveolar pattern in otherwise solid, undifferentiated rhabdomyosarcoma, must be classified as alveolar rhabdomyosarcoma. Cases of alveolar rhabdomyosarcoma showed a higher incidence of local recurrence, lymph node metastasis, distant metastatic spread, and death, than did cases of embryonal rhabdomyosarcoma. It is concluded that "cytological differentiation" does not improve the prognosis of rhabdomyosarcoma. PMID- 4036366 TI - [Ultrashort segment Hirschsprung disease. An objective picture of the disease substantiated by biopsy]. AB - The enzyme histotopochemical characteristics of 18 cases with ultrashort Hirschsprung's disease - investigated during the past 20 years - are analysed. The aganglionic segment, having an extension of 1-3 cm, is characterised by an increase of acetylcholinesterase activity in parasympathetic nerve fibres of the muscularis mucosae. A similar increase of acetylcholinesterase in the nerve fibres of the lamina propria mucosae - as characteristic in Hirschsprung's disease - is usually absent. Strip biopsies which include mucosa of the linea dentata and the distal rectum often show the transition from the aganglionic to the innervated mucosa. To avoid a faulty diagnosis by overlooking an ultrashort Hirschsprung's disease, it is recommended to take the first biopsy from the linea dentata, and biopsies 1 cm, 2 cm and 4 cm above this level, or to conduct a strip biopsy of 1-2 cm length taken from this area. 2/3 of the cases investigated were diagnosed during the first year of life. In 1/3 of the cases the diagnosis was made in patients who were 4 to 21 years of age. The average incidence of the ultrashort Hirschsprung's disease is 10% in relation to all aganglionoses studied. In recent years, however, diagnosis of this particular rectum disease was made more often (14%) due to a better knowledge of the disease (6.8% of all investigated inborn innervation failures of the colon). Ultrashort Hirschsprung is a rare disease, although it is observed more often than total aganglionosis of the colon (Zuelzer-Wilson syndrome). The sex ratio, being 5 male male: 1 female, is within the range of Hirschsprung's disease. Hence, enzyme histotopochemical means enable substantiation of ultrashort Hirschsprung's disease as a special form of an aganglionosis of the distal rectum. PMID- 4036367 TI - Abdomino-extended sacroperineal approach in high-type anorectal malformation--and a new operative method. AB - From 1971 onwards we have been examining the anatomy and histology of sphincter components in patients with several anorectal malformation who died of associated anomalies. These histological studies demonstrated that not only puborectal muscle but also the superficial and deep external sphincters exist, even in the high type anomalies, and that the mass of external sphincter is located above the anal dimple. Moreover, the inner circular muscle of rectum is thickened at the level of the closest part of the fistula. Based on our histological studies, we devised our new operation to use all the sphincter musculature effectively for the newly reconstructed anal canal. Our new surgical procedure is clearly different from Kiesewetter-Rehbein's method in that the puborectal muscle is penetrated from the outside of rectal wall and might be damaged, since puborectal muscle is attached to the blind pouch of rectum. Moreover, the puborectal muscle and the external sphincters can be easily identified by electrical stimulation under direct vision from extended sacroperineal approach. And the colon can be pulled exactly through the centre of the external sphincters and puborectal muscle under direct vision without causing any damage to these important sphincters, unlike Pena's operation. PMID- 4036368 TI - Childhood urolithiasis in Iran: a comparative study on the calculi composition of 121 cases. AB - Within 12 years, 165 cases of urolithiasis were observed at the Children's University Hospital of Teheran. The incidence of urolithiasis amounts to 1 case in 300 paediatric hospitalizations. 160 calculi from 121 children were analysed by various methods: semiquantitative chemical analysis (Mercognost), x-ray diffraction, polarising microscopy on thin sections. In about 25% of the cases metabolic disorders or malformations were found responsible for urolithiasis. In 100 cases, stone formation was attributed to the upper and in 21 cases to the lower urinary tract. Calcium oxalates are the most frequent constituents, followed by ammonium acid urate. The core of the stones in the upper tract was mostly composed of calcium oxalate. Ammonium acid urate was the second important core component, but occurred especially enriched in the lower urinary tract. On the basis of these and literature data, the lack of ammonium acid urate in juvenile stones in Europe and the USA seems surprising. Thus, it must be assumed therefore, that ammonium acid urate is a key to understanding the formation of endemic calculi. The cases studied support that with increasing standard of living, the incidence of bladder stones decreases. PMID- 4036369 TI - Technique of covering the raw surface of the spleen after partial splenectomy. PMID- 4036370 TI - [Anemic infarct of the liver following blunt abdominal trauma]. AB - Particularly in childhood, ischaemias of the liver are very rare. This is due to numerous collateral vessels and a dual blood supply of the liver. We, therefore, report on a 2-year old boy who suffered from an anaemic infarction of the whole left lobe of the liver after a fall. The clinical course and findings, including histology, are described. After resection of the left lobe the boy was free of symptoms. PMID- 4036371 TI - Purpura fulminans in neonates and childhood. AB - Three cases of purpura fulminans are reported. A five-year-old boy was successfully treated for purpura fulminans but had autoamputation of both legs and autolysis of bladder and urethra. He did not show any sign of shock at the onset of the disease. However, before an irreversible change of the skin lesion and organ involvement occurred, prompt diagnosis was effected, and aggressive treatment was given. An eight-day-old girl suffered from purpura fulminans at her four extremities, skull, bladder, ovary and vagina. Interesting findings were obtained in case 2, who had a positive family history. Several black spots in the extremities had disappeared spontaneously before admission, whereas the other lesions got progressively worse, with subsequent severe attack. Her general condition was not parallel to the severity of the disease. A 20-day-old boy had purpura fulminans after severe aspiration pneumonia, and showed a typical clinical course of the disease. In all patients, sudden drop of Hb and leukocytosis occurred after the skin lesion appeared. The diagnosis was unequivocal in these cases. Clotting time and FDP were good indicators of the progress of the disease in conjunction with the clinical features. Prompt diagnosis and aggressive therapy are necessary, not according to the patient's condition, but according to the laboratory findings and the serious nature of the disease. Internal haemorrhage must be considered as well as the skin lesion, this being a fatal complication. PMID- 4036372 TI - Closed loop intestinal obstruction due to vitello-intestinal remnants. AB - Two young children presented with acute small bowel obstruction associated with closed loop ileal obstruction caused by Meckel's diverticulum and vitello intestinal duct remnant respectively. In each, resection of the vitelline remnant and ischaemic ileum with primary small bowel anastomosis resulted in good recovery. PMID- 4036373 TI - [Understanding the life history: diagnostic, therapeutic and methodologic viewpoints]. AB - The concept of "life history" is the theme of this discussion. Working from a selection of therapy models (Duhrssen, Cremerius, Loch, Kohut, Morgenthaler) it can be shown that in every therapeutic approach various segments from the problem area of life histories in general can be isolated, developed and made into the central point of therapeutic activity. The relevant consequences for diagnosis, therapy and research will be clarified with respect to present-day movements in therapeutic psychoanalysis (ego-psychology, the analysis of narcissism, hermeneutic psychoanalysis). PMID- 4036374 TI - [Psychosomatic reactions to the experience of near death. A state of affective dissociation]. AB - The feelings of persons who had encountered life-threatening danger were analysed and compared with the feelings of persons, who are in hypnosis or trained in autogenic training. The symptoms are widely alike. The result of the comparison is, that there exists a state of affective dissociation, which can be caused by conscious or unconscious actions. PMID- 4036375 TI - [Psychodiagnostic studies in dialysis patients of a center and a limited care facility]. AB - In order to find out how far center hemodialysis (ZD) and limited-care hemodialysis (LCD) influence adjustment and being of the afflicted persons, 21 ZD patients and 19 LCD-patients were examined psychodiagnostically with the following tests: Rosenzweig Picture-Frustration Study, Taylor's Manifest Anxiety Scale (adapted to German conditions), and Freiburger Personlichkeits-Inventar. By means of statistical analysis it could be shown that the hemodialysis patients do not present themselves to their fellow-men in accordance with their real thinking and feeling. This behaviour brings on the peril of deviating attitudes which can affect their vigour. The LDC-patients gave much more indications of autonomous self-responsibility than the ZD-patients did. Psychotherapeutic efforts primarily should counteract regressive tendencies. PMID- 4036376 TI - [Stress in the life of Nigerian diabetics]. AB - The authors set out to answer the question (a) whether there are stress conditions in the life histories of Nigerian diabetic patients and (b) whether diabetic patients have complaints which have psychiatric significance. With regard to the first question, important biographic data of 54 diabetics were elicited. A constellation of significant stressful life situations was found among the diabetics such as early loss of father, being first borns, born of polygamous parents, being themselves polygamous, being the children of the first wives, and producing many children without having the adequate professions to yield the necessary financial resources to train them. Loneliness was not seen as part of these stressful life situation since almost all of them were married. With regard to the second question, the Enugu Somatization Scale was administered to the above mentioned diabetics (n = 54). It was found that about 37% of the diabetics have somatic symptoms which are indicative of psychiatric disturbance. PMID- 4036377 TI - [Diagnosis of primary hyperparathyroidism by selective determination of parathyroid hormones]. AB - Due to a hypercalcaemia and changeably appearing hypercalciuria 13 patients with relapsing urolithiasis were under suspicion of a primary hyperparathyroidism. After selective sounding and withdrawal of blood from the cervical veins in all cases the determination of parathormones was performed and always an increased activity of parathormones was found. The exploration of the cervical region carried out could in 11 performed operations in 8 cases prove an adenoma and in 3 cases a hyperplasia as cause of hyperparathyroidism. A localization of the suspected adenoma was in 5 cases possible in combination with the angiography of the thyroid gland. By equally high activity in 3 cases no clear evidence was possible. An improvement of the diagnostics of localization might be achieved by supraselective sounding of the veins. On principle the authors recommend to perform a selective determination of parathormones before operation, which in case of need is to be supplemented by a selective angiography of the thyroid gland. PMID- 4036379 TI - [Operative treatment of vesicovaginal fistulas and defects]. AB - On the basis of 15 own cases the problems of the operative treatment of vesicovaginal fistulae and defects are explained. In particular it is referred to those criteria which are of importance for the success of the corrective operations. PMID- 4036378 TI - [Modification of the risk of urolithiasis by changes in magnesium and calcium concentrations in the urine as affected by stress conditions]. AB - Under defined stress conditions, a slight decrease in the calcium concentration in the urine of calcium oxalate stone patients on the first and second experimental days was observed. Taking simultaneously recorded calcium concentrations into consideration, Ca/Mg quotients, were calculated, which, at least in single cases, exceed the limiting range, thus signalling an increased risk of calculus formation. PMID- 4036380 TI - [Inflammatory diseases of the kidney and efferent urinary tract]. AB - On the basis of a specific definition a summarizing description of the inflammatory diseases of the kidney and the efferent urinary tract is given. Apart from the description of the bacteriology of the infections of the urinary tract the author particularly deals with the significance of the asymptomatic bacteriuria, the acute bacterial cystitis, the acute pyelonephritis as well as the reflux nephropathy. Besides proposals for therapy references are given to the conduction of the patients after treatment. In the description of the chronic interstitial nephritis the nephropathy by analgesics is emphasized as most common disease. PMID- 4036381 TI - [Dissecting aneurysm as a rare vascular disease and its significance in urologic differential diagnosis]. AB - On the basis of two casuistics reference is made to the diagnostic difficulties of an aneurysm of the abdominal aorta with urological symptoms. A frequently empty urological anamnesis, oligo-anuria, colic-like pains in the medium epigastrium with pulsating tumour and an increasing acrocyanosis in the region of the lower extremities are an imperative reason to think of an aneurysm of the abdominal aorta, including the two renal arteries. PMID- 4036382 TI - [Cancer of a renal cyst wall]. AB - It is reported on three cases of cyst wall carcinomata in altogether 202 patients (= 1.5%) in whom a resection of the cyst wall was clinically indicated. Only in one case there was preoperatively an angiographically proved suspicion of the presence of a cyst wall carcinoma. Since there do not exist any exact methods for proving cyst wall carcinomata and the slight size of the tumour does not evoke systemic, unspecific tumour signs, their evidence remains depending upon accidentally found, discrete changes in the picture-producing techniques. PMID- 4036383 TI - [Therapy of testicular tumors in childhood]. AB - Between 1954 and 1984 41 primary testicular tumours were treated in 40 children at the age of 0 to 9 years as well as 9 secondary testicular tumours in malignant systemic diseases or metastases. The histological reclassification of the number of cases revealed 15 yolk-sac-tumours, 10 differentiated teratomas of immature subtype, 1 intermediary malignant teratoma, 3 undifferentiated malignant teratomas, 2 Sertoli-cell-tumours (1 double-sided) and 5 rhabdomyosarcomas. 2 children each with undifferentiated malignant teratomas and rhabdomyosarcomas died, all before 1970. 5 children with yolk-sac-tumours and 2 with rhabdomyosarcomas who since 1974 have been treated with Ablatio testis and combination chemotherapy live without tumour. Histological classification and division into stages are proved and form the basis of a therapy conception which in all testicular tumours apart from the Ablatio testis contains the chemotherapy of different intensity (HTK-84), taking into consideration form of tumour, stage and age of the children. The retroperitoneal lymphadenectomy is recommended only in the proof of metastases. PMID- 4036384 TI - [Mature teratoma following chemotherapy in bilateral testicular tumors--a critical contribution]. AB - The histological treatment of preparations of the retroperitoneal lymphadenectomy (RLA) after chemotherapy of non-seminomatous testicular tumours results in about 25% of the cases in the evidence of the "mature teratoma". An own observation suggests that a prognostically favourable valuation of this diagnosis is justified not without restriction. PMID- 4036385 TI - [Possibilities for the use of exfoliative urine cytology in invasive and noninvasive bladder cancer]. AB - In invasively growing tumours of the urinary bladder specificity and sensitivity of the urine cytology are sufficiently high with 100 and 66%, respectively, it is, however, not successful. Endoscopy and histological ascertainment are now as ever prevailing (TUR). Cytology is indispensable to the diagnosis of the carcinoma in situ of the urinary bladder. In non-invasive urothelial carcinomas the classification of the WHO after Friedell stands the test. It is also shown a better correlation to the cytological findings which more frequently become positive with growing degree of malignity. High degree of malignity, multiple tumours and positive cytology are to be valuated as particular risk factors concerning frequent relapses and their appearance of invasively growing tumours. The domain of cytology is the control of the course with curative aim of patients who were operated on in order to sustain the organ. Relapses are frequently more dedifferentiated than the primary tumour so that the recidivation is often indicated cytologically. The endoscopic demonstration of the recidivation may still be absent at the beginning. Also for controls under local chemotherapy cytology stands the test, in which cases we may not sufficiently judge the value of this treatment method due to the small number of cases. PMID- 4036387 TI - [Difficult new beginning 40 years ago (1945/1985)]. PMID- 4036386 TI - UV-repair and mutagenesis in Azotobacter vinelandii. II. Repair and mutagenesis. AB - More numbers of mutants were isolated when UV-irradiated cells of Azotobacter vinelandii OP were treated with caffeine for a limited period of time after UV irradiation. This is encouraging, considering the difficulty in isolating Azotobacter mutants. Post-irradiation treatment with acriflavine, however, yielded comparatively lesser number of mutants. PMID- 4036388 TI - [Significance of fracture form and bone necrosis for the treatment of open tibial fracture]. AB - In a retrospective analysis the author deals with 370 open fractures of the tibia which were administered from 1961 to 1980. Treatment by plate osteosynthesis proved to be superior to conservative management (13% wound infections, 11,3% aseptic complications). Special importance is attached to the degree of soft tissue damage as a cause of osteonecrosis in certain types of fractures. By presenting a new classification scheme of fractures of the tibia the author is able to derive that kind of treatment which is required. PMID- 4036389 TI - [Femur shaft fractures in artificial hip joint replacement]. AB - In a total of 1980 patients who underwent total hip replacement 0.8% suffered from intra- and postoperative fractures of the femoral shaft. These spontaneous fractures were preconditioned by damage of the cortical layer due to rheumatoid arthritis, aseptic and septic looseening of the prosthesis as well as local trauma. In most cases stability could be restored by plate osteosynthesis, sometimes in combination with change of the prosthesis. PMID- 4036390 TI - [Space-occupying processes in the spine in tuberculous spondylitis]. PMID- 4036391 TI - [Replantation surgery--specific problems, organization and results]. PMID- 4036392 TI - [The new Charite building and the University Surgical Clinic]. AB - The new multi-storey hospital of the Humboldt-University in Berlin has a capacity of 1050 beds, encompasses a surgical clinic with 312 beds, 11 theatres and its own unit for intensive care. All kinds of modern surgery can be performed in its 7 specialised wards. PMID- 4036394 TI - [Catheter peridural anesthesia in serial rib fractures]. PMID- 4036393 TI - [Diagnosis and surgical therapy of lung sequestration]. PMID- 4036395 TI - [The histologically evaluated accuracy of lymphography in operative therapy of invasive cervix cancer stages Ib-IIb]. AB - 118 of 129 pre-operative patients with invasive cervical carcinoma of stage Ib to IIb from 1974 to 1978 were examined lymphographically. Abdominal radical hysterectomy according to Wertheim with obligatory lymphonodectomy followed in all cases. Results of the histologic examination of lymphnodes have been compared with the findings from lymphography, whereby a coincidence could be proved in 84 per cent of all cases. The correlation for the lumbar and iliac lymphonodi was listed separately in 75 per cent of the cases. Lymphography gives significantly better results within the lumbar region with an accuracy rate of 92 per cent, a sensitivity of 100 per cent and a specificity of 98.5 per cent. It may be concluded that a lumbar lymphonodectomy is not necessary in the event of a negative lymphography. PMID- 4036396 TI - [Clinical aspects and results of therapy in endometrial cancer at the Department of Medicine of the Friedrich Schiller University in Jena 1964-76. I: Evaluation of primarily surgically treated endometrium cancer]. AB - In this paper therapeutic results are reported obtained from 444 patients with endometrial cancer which were operated on. In 260 patients the primary operation was completed by a different radiation therapy. The 5-years-survival rates are 75,9% Surgical and radiological therapeutic measures are demonstrated with regard to their development and to side effects. PMID- 4036397 TI - [Unilateral Mayer-Rokitansky-Kuster-Hauser syndrome (unilateral Mullerian dysgenetic syndrome)]. AB - A case of unilateral Mayer-Rokitansky-Kuster-Hauser-Syndrome is reported. Anatomical and etiopathogenetical aspects of the syndrome and a review of the literature are presented. PMID- 4036398 TI - [Therapy and course of a malignant double melanoma]. AB - A report is given on the treatment and course of disease of a 38-year-old patient suffering from a malignant melanoma (m. m.) of the vagina and of the left lower eyelid. In view of the unfavourable prognosis the achieved survival time of 79 months may be attributed to radical surgical treatment and additional combined chemotherapy. PMID- 4036399 TI - [Prolapse of the small intestine through the vagina following repeated gynecologic operations]. AB - A case of prolapse of the small bowel through the vagina after gynaecologic operations is described. This is a very rare complication and up to date only eleven cases have been described. Measures to prevent this complication are discussed. PMID- 4036400 TI - [Consequences of family oriented obstetrics]. AB - Attitudes toward motherhood are defined as well by the individual life history and learning process as by the social situation of the pregnant women. The mother child-relationship can be supported by the hospital routine if there is offered: individual pregnancy care, to pay more attention to personal situation of the becoming mother, psychological childbirth classes for the becoming parents, early skin contact between mother and the newborn, rooming-in and hospital visits for the brothers and sisters. PMID- 4036401 TI - [Measurement of uteroplacental circulation with 113m indium in diabetic pregnancy]. AB - In 122 diabetic pregnancies the placental blood flow has been estimated determining the half life of the activity inflow (2 MBq 113 m In labelled transferrin) into the placental bed. We used a highly sensitive detector (modified pinhole collimator) and a computer supported evaluation, free from subjective influences. 259 flow measurements were compared to the risk of complication in the course of a diabetic pregnancy. - The half life values in the diabetic group, calculated by a gamma camera computer system by means of an iterative regression analysis, were significantly different compared to a control group (12 pregnancies without risk.) - Severe diabetic angiopathic complications (White classes D, F, and R) are accompanied by higher half life values (placental blood flow reductions) and perinatal complications. - Even in pregnant women with gestational diabetes or disturbances of the carbohydrate metabolism a disturbed placental hemodynamic is to be found. PMID- 4036402 TI - [Analysis of very underweight newborn infants (less than 1,500 g) 1972-1982. Epidemiologic aspects, labor presentation, position and adjustment, method of delivery and mortality]. AB - Infants with a very low birthweight (less than 1500 g) have a fundamental influence on perinatal mortality and mortality of babies up to one year also nowadays. The epidemiological role of different signs of risk in the context of the birth of these children is presented. The total mortality of the infants with a very low birthweight (less than 1500 g) was 64,4%. Usually there were combinations of factors, which caused the death of the infants. Complications of secundinae, immaturity and malformations were the substantial factors of lethality of the stillbirths. At the mortality of babies there were intracranial bleedings and immaturity (less than 1000 g, less than 28 completed weeks of pregnancy) in the foreground of the causes of death. PMID- 4036403 TI - [Thrombocytopenia in pregnancy]. AB - The rare occurrence of thrombocytopenia in pregnancy is reported. Our own procedure in pregnancy and delivery is described in detail. The differential diagnostic considerations are emphasized. The present situation with regard to therapy is discussed with reference to the available literature. PMID- 4036404 TI - [Effectiveness of postoperative spa treatment at Bad Elster in patients with tubal sterility]. AB - A survey of a gynecological therapy strategy is described. The results of postoperative cures at a spa (Bad Elster) in 69 women, suffering from tubar sterility, were investigated by means of physical examinations and questionnaires. It was found, that the number of pregnancies (8,7%) did not increase. - There was an improvement in state of health. PMID- 4036405 TI - [Is cryosurgery as alternative treatment procedure for recurrent hyperplasia of the endometrium in perimenopause to be considered?]. AB - Complex investigations were performed for the evaluation of the local biological effect of the total cryodestruction of endometrium in 7 perimenopausal women with relapsing hyperplasia of the endometrium before and after (in 3-4.5 months) surgery. The following methods were used: radiometry of uterus, cytomorphologic and cytomorphometric investigations, RIA of E2 in peripheral blood plasma, in cytosol and in a nuclear fraction, and an assay of the state of E2-receptor endometrial system. The results of the investigations showed the importance of these methods as the objective criteria for the treatment efficiency. It was established that the cryosurgery is an alternative method for the treatment of this pathology in perimenopausal women. PMID- 4036406 TI - [Value of the dexamethasone-mestranol-HCG test for the differential diagnosis of forms of hirsutism]. AB - 20 patients with hirsutism of different severity were examined to study the diagnostic assertion of the dexamethasone-HCG-test. The results show, that a well defined classification into the different types of hirsutism (adrenal, ovarian, idiopathic and mixed forms) is not possible using hormonal parameters. PMID- 4036408 TI - [Fertility and Turner syndrome]. AB - A case of Turner's syndrome (45,X/47,XXX) with one pregnancy is reported. Review of the literature revealed additional 31 cases of fertility in women with gonadal dysgenesis associated with a 45,X chromosomal line. Abortion and stillbirth are frequent and the rate of malformation is high. PMID- 4036407 TI - [Bromocriptine therapy of prolactinoma in pregnancy]. AB - A report is given about the course of pregnancy and delivery of two patients with prolactin-producing pituitary adenomas and therapy with bromocriptine. Different views about treatment of prolactinomas in pregnancy are discussed. Pregnancy care has to be in close cooperation between endocrinologists and obstetricians. PMID- 4036409 TI - [Automatic analysis of the spectra of extracellular proteins based on their autocorrelation characteristics]. AB - Hardware and software for the automatic comparison of densitograms, based on the evaluation of their autocorrelation characteristics, can be used for establishing the characteristics of circulating staphylococcal populations and for their epidemiological marking. PMID- 4036410 TI - [Epidemiological surveillance--the basis of the modern organization of epidemic control work]. PMID- 4036411 TI - [Frequency of detecting HBsAg among pregnant women living in different regions of the Soviet Union]. PMID- 4036412 TI - [Antibody avidity indices of the saliva and serum antibodies in salmonellosis patients]. AB - The avidity characteristics of salivary and serum antibodies have been determined in 179 salmonellosis patients by means of the indirect hemagglutination inhibition test. These investigation have shown that, in contrast to serum antibodies, no changes occur in the avidity of salivary antibodies in the course of the disease. This is due to the fact that secretory antibodies belong to IgA which have no tendency to ripening. The regularities thus established reflect the role of secretory and serum antibodies in the pathogenesis of Salmonella infections. PMID- 4036413 TI - [Assessment of peripheral blood monocyte function in pulmonary tuberculosis patients]. AB - As the result of the study of the peripheral blood monocyte function in patients with pulmonary tuberculosis, the ingestive capacity of monocytes has been found to be suppressed, which indicates the pathological state of oxygen-dependent mechanisms governing the bactericidal activity of cells, the most pronounced disturbances of monocyte functions being observed in patients with fibrous cavernous and disseminated tuberculosis. PMID- 4036414 TI - [Evaluation of the functional activity of peritoneal macrophages using the tetrazolium test]. AB - The redox activity of peritoneal macrophages has been evaluated in the modified NBT test using tetranitro blue tetrazolium. This method permits the calculation of the total amount of peritoneal macrophages and the determination of their glass adherence per cent and their cytochemical activity value. The advantages of this method over the study of the phagocytic activity by means of phage T2 is shown. PMID- 4036415 TI - [Detection of Mycoplasma arthritidis and Mycoplasma fermentans antibodies in rheumatoid arthritis patients by an immunoenzyme method]. AB - The optimum parameters of the immunoenzyme assay system for the identification of antibodies to M. arthritidis and M. fermentans in the sera of patients with rheumatoid arthritis have been established. The investigation has shown that the products obtained by the ultrasonic disintegration of the biomass of M. arthritidis and M. fermentans can be used as soluble antigens for adsorption on the polystyrene surface of plates. The use of the immunonenzyme assay, specially modified, has made it possible to establish that antibodies to M. arthritidis can be detected in 6.5% of cases, antibodies to M. fermentans, in 41.9% of cases and the association of antibodies to M. arthritidis and M. fermentans, in 41.9% of cases. At the same time antibodies to M. arthritidis have been found to belong mainly to IgM and antibodies to M. fermentans, to IgG or to IgG and IgM simultaneously. PMID- 4036416 TI - [Reserve potentials of immunity]. AB - The immunological examination of 350 top level sportsmen has been made at different stages of training and competitions. This examination has revealed that the reaction of the immune system to superextreme loading can be divided into 4 phases: activation, compensation, decompensation and restoration. In the process of adaptation to increasing muscular loading, characteristic of modern competitive sport, the reserves of the immune system are mobilized, and the immunological characteristics are thus maintained at the initial level. In some of healthy adults the action of superextreme physical and psychoemotional loading produces the exhaustion of immunity reserves, which is manifested by the disappearance of certain classes of immunoglobulin from the blood and biological secretions 1-2 hours after the cessation of this action. PMID- 4036417 TI - [Enzyme profile in the peripheral blood leukocytes in acute respiratory diseases]. AB - The character of changes in the enzymatic activity of peripheral blood leukocytes indicate the activity and severity of the process and may serve as data for the prognosis of the course of the disease and for the evaluation of the effectiveness of antibacterial and desensitizing therapy. PMID- 4036418 TI - [Changes in the cellular reactivity of guinea pigs sensitized with Bacillus thuringiensis]. AB - Changes in the cell-mediated responsiveness of the body under the action of different variants of B. thuringiensis have been studied in experiments on guinea pigs. The data thus obtained indicate that the development of sensitization occurs in the animals, which is manifested by the increase of the sensitivity of leukocytes to the specific allergen and by the increase of the phagocytic activity of peritoneal macrophages. The most pronounced changes in the immune responsiveness of guinea pigs have been observed after the parenteral administration of B. thuringiensis var. galleriae. PMID- 4036419 TI - [Erythrocyte reagents for detecting antibodies to species-specific staphylococcal antigens]. AB - Antigenic species-specifics (S. aureus and S. epidermidis) erythrocyte diagnosticums have been obtained with the use of different loading methods. The cross reaction of passive hemagglutination with homologous and heterologous sera have demonstrated that conjugation with amidole ensures the maximum effectiveness and species specificity of diagnosticums in comparison with other conjugation methods. PMID- 4036420 TI - [Histoautoradiographic study of synthesis of neuronal proteins of the brain in response to exposure to damaging factors during the prenatal period]. AB - The incorporation of 3H-leucine into the neuronal proteins of the hemispherical cortex and hyppocampus was studied in rats aged 1 and 3 months which were exposed to hypoxia and ethanol in the antenatal period. The test one-month-old animals showed activation of protein synthesis in neurons and in layers III and V of the cortex and hyppocampus. At the age of 3 months the rats showed inhibited incorporation of the label into neuronal proteins of the studied structures of the brain which was more expressed in animals which had suffered intrauterine hypoxia. PMID- 4036421 TI - [Effect of leponex on the ultrastructure of the brain]. AB - Electron microscopic examination of the black substance, olfactory tubercle and head of the rat caudate nucleus was made upon a single and a 3-week administration of the antipsychotic drug leponex in a dose of 10 mg/kg. It was shown that leponex induces hyperproduction of the mitochondria, changes in sizes and form of neuronal bodies and processes, and the formation of the membranous structures in presynaptic endings. These changes were attended by ultrastructural shifts in neurons and glia. The data are considered as compensatory processes of mediator receptors of the brain. PMID- 4036422 TI - [Morphologic changes in the nervous system in acute carbophos poisoning]. AB - The nervous system of 13 patients who died of an acute oral intoxication with carbophos was subjected to morphological examinations. Vascular changes were expressed as congestive plethora, perivascular edema and microfocal hemorrhages. Cellular abnormalities mainly included acute swelling, severe ischemic and hydropic alterations. Pathomorphology of the fibers was manifested in foci of secondary demyelinization in the internal capsule, lateral columns of the spinal cord and the peripheral nerves of the extremities. PMID- 4036423 TI - [Effect of hyperbaric oxygenation on the course of experimental brain edema]. AB - The authors studied experimental brain edema and morphological changes in the cerebral tissue in 2 groups of animals: the test group receiving hyperbaric oxygenation (HBO) and the control group. The test animals showed a more favourable course of brain injury. Microscopic examination revealed a lesser degree of brain edema and intensification of reparative processes in the cerebral tissues of animals receiving HBO. PMID- 4036424 TI - [Diagnostic significance of immunologic study of cerebrospinal fluid in neuroinfections]. AB - An increase in the antibody titre in the blood serum, previously considered sufficient for determining the etiology of neuroinfection can no longer be regarded as a satisfactory index in the light of the contemporary level of our knowledge. The literature and the authors' own data show the importance of a simultaneous examination of antibodies in the cerebrospinal fluid and the blood serum in some neuroinfections. For example, the determination in the cerebrospinal fluid of antibodies to herpes simplex virus in herpetic encephalitis is considered sufficient (in the presence of the characteristic clinical picture) to make the diagnosis of this severe disease. The examination of antibodies to herpes simplex virus in the cerebrospinal fluid of 35 patients with a suspected herpetic encephalitis revealed their presence in 34% of those studied. The data obtained suggest that immunoassay of the cerebrospinal fluid and blood sera should be used on a broader scale in patients with acute and chronic neuroinfections. The method plays an the early diagnosis of these diseases and early administration of the appropriate treatment. PMID- 4036425 TI - [Diagnosis of trigeminal neuralgia predominantly of central and predominantly of peripheral origin]. AB - The authors examined electrical conductivity of acupuncture points on the face of 60 patients with trigeminal neuralgia. The results permitted the development of differential diagnostic criteria of trigeminal neuralgia of predominantly central and predominantly peripheral genesis. PMID- 4036426 TI - [Tibiopedal reflex]. AB - The tibiopedal reflex is described in detail. The clinical significance of the reflex is specified, which is determined by its ability to differentiate nervous system lesions different in terms of their localization and nosology. PMID- 4036427 TI - [Has psychopharmacotherapy had any effect on the chronicity of mental patients? (apropos of the article by A.B. Smulevich and G.P. Panteleev)]. PMID- 4036428 TI - [Morphology of the epileptic neuron]. AB - Using electron microscopy, the authors studied neurons and their synapses in the cortical foci of the brain in patients (1) with brain tumours attended by epileptic seizures, (2) with tumours accompanied by no paroxysms, and (3) with epilepsy of unknown etiology. The material was obtained in the interparoxysmal period. Morphometric study of the ultrastructure showed that morphological changes characteristic of epileptization were determined only in axodendritic (AD) and axospinal synapses in the form of their massive activation whose degree was calculated by collating the area of the "active zones" with the area of the entire synaptic surface. In epilepsy this ratio was 10-12 times higher than in tumours unattended with seizures. Activation of AD synapses should be considered as an ultrastructural manifestation of epileptization of the neuron while its extension should be seen as a criterion of the morphological diagnosis of the disease itself. PMID- 4036429 TI - [Various patterns in structural changes in the cortex and subcortical structures of the human brain during the aging process]. AB - The authors examined the structural organization of cortical and subcortical formations (fields 4, 6, 8, 44, 47, 39, the head of the caudate nucleus and thalamic nuclei) of the right and left hemispheres of the brain of 6 mentally normal subjects aged 30 to 90 years. In sections 20 millimicron thick and stained by Nissl's method the authors measured the density of neurons in subcortical nuclei, in layers III and V of the cortical fields, as well as the number of neurons containing lipofuscin. The identified characteristics indicate heterochronicity of the process of ageing in different portions of the brain: motor and, particularly, cortical structures are involved in this process earlier and more intensively than others. PMID- 4036430 TI - [Various quantitative characteristics of the pathoarchitectonics of the cerebral cortex in Pick disease and Alzheimer disease]. AB - On the basis of the study of the pathological architectonics of 6 brain hemispheres in Pick's disease (PD) and 4 hemispheres in Alzheimer's disease (AD), the author presents data on changes in the size of the surface of the hemispheres on the whole and of individual areas and compares them with the mean figures. It is concluded that the degenerative, atrophic process in both groups of presenile dementia involves the entire brain cortex: the indices of the area of the entire hemisphere in all the cases studied were below the mean values. The surface of the cortex was shrinked in both phylogenetically new areas (inferior occipital, frontal and temporal) and phylogenetically older regions (pre- and postcentral, occipital), as well as in the limbic and insular regions. In all cases the general regularity was maintained: a decrease in the size of the entire hemispherical surface as well as individual regions was more expressed in AD than in PD. The exception to this rule was 1 case of PD in which all parameters were very low which may be associated with the duration of the disease (12 years). There was a certain asymmetry between the size of the hemisphere on the whole and of its individual regions. No correlation was found between the degree of macroscopic atrophy of the convolutions and the severity of pathological achitectonic changes in cortical formations. PMID- 4036431 TI - [Muli-infarct dementia]. AB - Two hundred and fifty-five cases of dementia of advanced age were studied. In 142 of them (56%) the clinical diagnosis was vascular dementia. In 55 the anatomical diagnosis was senile dementia or Alzheimer's disease and in only 40 cases with established multiple infarcts (in 38 cases they were localized in the area of the subcortical ganglia) the diagnosis was multiinfarction dementia. In 11 of these 40 cases, multiinfarction dementia was combined with senile dementia and Alzheimer's disease. In relation to all 255 studied dementias of advanced age multiinfarction dementia constituted 11% in its pure form and 18% in its mixed form. PMID- 4036432 TI - [Features of changes in vessels of the cortex and white matter of the cerebral hemispheres in arterial hypertension]. AB - The authors examined morphologically the arteries of the surface and intracerebral arteries of the cortex and white substance of different areas of the cerebral hemispheres in 11 necropsies of patients with arterial hypertension who died from hemorrhagic strokes. It was established that arteries of the cerebral surface 200-500 micron in diameter were characterized by compensatory adaptive processes reflecting structural adaptation of the vessels to a prolonged elevation of blood pressure. The intracerebral arteries were considerably more frequently characterized by changes induced by hypertonic crises expressed in the form of plasmorrhagias and isolated necrosis of the tunica media. The cortico medullary arteries 100-150 micron in diameter were predominantly affected which accounts for a more severe damage to the cerebral white substance in arterial hypertension. PMID- 4036433 TI - [Morphology of disorders of cerebral circulation in the white matter of the cerebral hemispheres in the newborn infant]. AB - The author examined histologically the white matter of the brain hemispheres in 29 mostly immature children who died within 3 days after birth. The newborns were grouped by the following kinds of damage to the white substance of hypoxic and ischemic nature associated with disorders of the cerebral hemodynamics: endemous hemorrhagic leukoencephalopathy (EHL), periventricular telencephalic gliosis (PTG), periventricular leukomalation (PL), periventricular hemorrhagic leukomalacia (PHL) and cerebral hematomas. Certain similarity in the topography of lesions in EHL, PHG, PL and PHL was established. The most considerable lesions were found in the periventricular white substance of the initial portions of the posterior corns. PMID- 4036434 TI - [Acetylcholinesterase activity in the brains of rats in a model of alcoholic embryopathy]. AB - Acetylcholinesterase (ACE) activity was studied by the Karnovsky-Ruts method from the 5th to the 30th day in the brain of young rats born to chronically alcoholized animals receiving ethanol for 3 to 5 months prior to conception as well as during pregnancy and breast feeding. Alcohol was found to induce deviations in the formation of the enzyme in the adjacents nucleus and Broca's diagonal strip on days 5 and 20 of the postnatal development, respectively. It is assumed that the above deviations are involved in manifestations of the alcoholic syndrome of the fetus. PMID- 4036435 TI - [Results of creating extra-intracranial arterial anastomoses in occlusive diseases of the vessels of the brain]. AB - The article analyses the results of operations for creating end-to-side extra intracranial anastomoses between the branches of the external carotid artery and cortical branches of the middle cerebral artery in 62 patients with occlusion of the cerebral vessels and in 3 patients with giant aneurysms of the supraclinoid part of the internal carotid arteries. PMID- 4036436 TI - [Hyperbaric oxygenation in ruptured cerebral aneurysms during the postoperative period]. AB - The OKA-MT pressure chamber was used. The course consisted of 6-15 sessions at a pressure of 1.6-2.0 at. abs. Hyperbaric oxygenation (HBO) was included in the complex of therapeutic measures applied in the postoperative period in patients with ruptured aneurysms of the cerebral vessels. From comparison of the course of the disease in 47 patients treated by HBO with that in 30 patients not subjected to HBO (control group) the authors conclude that the inclusion of HBO in the complex of measures applied after operations on the cerebral vessels for ruptured aneurysms has a positive effect on the course of the disease: the grave condition is less prolonged; the duration of the meningeal syndrome, headache, and temperature reaction is shorter by 6 days than in the control group; the number of patients with a good result of treatment increases by 18%; mental disorders in the absence of hematoma of the frontal area are prevented; the frequency of suppurations of the postoperative wound diminishes. PMID- 4036438 TI - [Computer tomography in the diagnosis of neurinomas of the acoustic nerve]. AB - Computer-aided tomography (CT) was used in the examination of 259 patients with neurinoma of the acoustic nerve. Characteristic direct and indirect signs of the tumor and the degree of their manifestation depending on the size and predominant direction of the growth of the neurinoma were determined. In 46 patients the size of the tumour established by computer-aided tomography was compared with that revealed on operation. It was established that computer-aided tomography demonstrates exactly the true size of tumors whose compactness is greater than that of the brain matter. It is difficult to determine by CT the true size of tumors of low density and particularly those possessing isodensity; in some cases they are much larger than conceived from analysis of the computer-aided tomograms. Tumors less than 10 mm in diameter which cannot be recognized by ordinary CT can be diagnosed by CT and cisternography with amipak. PMID- 4036437 TI - [Microcirculation in the brain during controlled arterial hypotension. Experimental study of the effect of nipruton]. AB - The effect of nipruton (sodium nitroprusside)-induced controlled arterial hypotension on the intracerebral microcirculatory channel was studied on 4 rabbits with transplanted induced tumors (anaplastic astrocytomas) and 7 intact rabbits under general anesthesia. It was found that nipruton injected in doses necessary for marked reduction of arterial pressure (35-45 mm Hg) for a sufficient duration (30-55 minutes) causes no circulatory disorders in the brain. In animals with tachyphylaxis to nitropruton, in which the amount of the injected agent must be increased to 9-10 mg/kg, controlled arterial hypotension even of lesser depth (60-65 mm Hg) and lesser duration (20-25 minutes) can lead to partial obstruction of the intracerebral microcirculatory channel. i. e. to the no-reflow phenomenon. PMID- 4036439 TI - [Waya and methods of treating malignant glial tumors of the cerebral hemispheres]. PMID- 4036440 TI - [Methodologic problems in studies of pressure in the venous sinuses of the brain]. AB - The adequacy of the indirect method for the liquorodynamic evaluation of intrasinusal pressure has been established. It was found that in patients with parasagittal meningiomas intrasinusal pressure does not depend on the size of the tumour and its relation to the superior sagittal sinus, or on intracranial hypertension (up to 28 mm Hg). In the phase of decompensation of intracranial hypertension the effective pressure of resorption increases. The quantitative characteristics of venous cerebral circulation and of liquorodynamics is of importance in evaluating the condition of compensatory mechanisms of the cerebrospinal system in various forms of neurosurgical pathology. PMID- 4036441 TI - [Periarterial alcoholization of the vertebral artery in vertebrogenic lesions]. AB - Periarterial alcohol-procaine blockade causes an effect similar to that of procaine blockade; it improves the supply of blood not only to the brain stem but also to the anterior parts of the brain through removal of the neuroreflex influences and improvement of collateral circulation. It causes stable improvement of the patient's condition, particularly in dystonic and dystonic ischemic stages of the vertebral artery syndrome. The results of clinical study allowed indications to be formulated and revealed the absence of contraindications for the method of treatment elaborated. PMID- 4036442 TI - [Short-latency somatosensory evoked potentials in injuries of the cervical division of the spinal cord]. AB - Short-latent cortical potentials and induced potentials (IP) recorded from the cervical spine in response to electrical stimulation of the median nerve on the wrist were studied in patients with injury to the cervical parts of the spine and spinal cord. The changes in the pronounced character of the somatosensory induced potentials (SSIP) proved to be more marked than those in the controls. A group of patients with considerable increase of peak N1 and corresponding increase of the time of conduction along the central nervous system (up to 20 msec) was distinguished. The latent period (LP) of IP recorded in the region of the cervical parts of the spinal cord was also prolonged in these patients. The pronounced character of the SSIP changes corresponded to that of the neurological disorders in these patients and the course of the subsequent restorative period. PMID- 4036443 TI - [Xenoplasty of the dura mater by means of formalinized grafts]. AB - The possibility of using as plastic material animal (neat cattle, pig) dura mater stored in 0.5% formaldehyde solution was studied. The structure of the dura mater tissue is maintained for a 3-year storage period, and it therefore can be used during this period. The results of experiments (on 30 dogs) and clinical observations (63 patients) show that dura mater grafts used to repair a defect ensure airtightness of the subdural space and separate the brain from the overlying tissues, thus preventing the development of an adhesive-cicatricial process. On resorption, the graft is replaced by an organ-typical regenerated material performing the function of the lost dura mater. PMID- 4036444 TI - [Experimental arterial microanastomoses]. AB - The morphological changes in the walls of 40 arterial microanastomoses were studied in experiments. The initial signs of endothelization appear in 3 days and the process ends by the 9th-12th day. The tissue reaction to the different suture material is of the same type and its degree is not linked with the type of synthetic thread used. Minimum injury inflicted to the intima and the other coats of the vascular wall and pre- and postoperative use of acetylsalicylic acid are measures preventing occlusion and stenosis of the anastomosis. PMID- 4036445 TI - Immunological analysis of histone H2A from the slime mold Physarum polycephalum. AB - Specific antibodies against the histone H2A from calf thymus were generated by injecting rabbits with complexes: histone H2A-RNA with a protein to RNA ratio of 3:1. In the microcomplement fixation assay the antibodies against the histone H2A from calf thymus immuno-reacted with the histone H2A from calf thymus but not with H2A from Physarum polycephalum. The histone H2A from calf thymus therefore appears to have an immunological determinant(s) which does not exist in H2A from Physarum polycephalum. PMID- 4036446 TI - Effect of thiol-reactive reagents on the permeability of fish erythrocyte membrane for spin-labelled non-electrolytes. AB - Carp erythrocytes were treated with p-chloromercuribenzoate or N-ethylmaleimide. It was observed that these thiol-group inhibitors decreased the transport of spin labelled hydrophilic compound, 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl, and increased the transport rate of more hydrophobic 2,2,6,6 tetramethylpiperidine-1-oxyl. PMID- 4036447 TI - 1-Amino-2-phenylethylphosphonic acid: an inhibitor of L-phenylalanine ammonia lyase in vitro. AB - L(-)-, and D(+)-enantiomers of 1-amino-2-phenylethylphosphonic acid (PheP), a phosphonic analogue of phenylalanine, inhibit the activity of L-phenylalanine ammonia-lyase (EC 4.3.1.5) of potato tuber tissue in vitro. The apparent type of inhibition depends on concentration of PheP; as the concentration of D-PheP is raised from 10(-5) M to 2.5 X 10(-3) M, the type of inhibition shifts from competitive through mixed and non-competitive to uncompetitive. L-PheP exerts either a competitive or mixed-type inhibition at low (10(-6)-10(-5) M) or moderate (5 X 10(-5)-2 X 10(-4) M) concentration. Ki for the concentration range of competitive inhibition were 6.5 X 10(-6) M, 5.3 X 10(-5)M and 1.6 X 10(-5) M for L-, D-, and D,L-PheP, respectively. These Ki values are valid for a relatively narrow range of L-Phe concentration (0.2-4 mM) as L-phenylalanine ammonia-lyase does not follow the Michaelis-Menten kinetics of the reaction. PMID- 4036448 TI - Terminal plasmin degradation products D and E of duck fibrinogen and their effect on polymerization of fibrin. AB - Duck fibrinogen (Mr 320 000) treated with streptokinase-activated human plasminogen in the presence of calcium ions was hydrolysed to terminal core fragments D and E. They were isolated from the digest by: (1) ion-exchange chromatography on DEAE-cellulose, (2) gel filtration on Sephadex G-100, and (3) affinity chromatography with the use of fibrin monomers coupled to CNBr-activated Sepharose. When the native D fragment, D1 was additionally digested by plasmin in the presence of EDTA, more degraded forms D2 and D3 appeared. Molecular weight of D1, D2, D3 and E estimated on SDS-polyacrylamide gel electrophoresis is 100 000, 89 000, 80 000 and 50 000, respectively. It was found that after reduction with 2 mercaptoethanol the fragments D1 and D3 consisted each of three polypeptide chains: alpha, beta, gamma: the gamma-chain of D3 remnant was more degraded (Mr 24 000) as compared with the gamma-chain of D1 remnant (Mr 42 000). Polymerization of both duck and pig fibrin monomers was inhibited by fragments D1 but not by D3. PMID- 4036449 TI - UV light-induced changes in washed pig platelets. AB - The effect of ultraviolet radiation (UV-A, 360 nm) on the thrombin-induced aggregation of washed pig platelets as well as on the release of adenine nucleotides and proteins was studied. The level in platelets of adenine nucleotides, mainly ADP and ATP, decreased rapidly following the exposure of platelets to a high dose of UV-A (0.5 W/cm2, 30 min). Through thrombin-induced aggregation of irradiated platelets was inhibited, the release reaction occurred. The amount of the released adenine nucleotides and proteins was, however, dependent on the dose of UV light. These findings suggest that UV-A light can stimulate the platelet release reaction. PMID- 4036450 TI - Methionine synthase assay based on coupling with thymidylate synthase reaction. AB - Methionine synthase reaction may be coupled with thymidylate synthase-catalysed tritium release from [5-3H]dUMP via non-enzymatic reaction of formaldehyde with tetrahydrofolate. A convenient and sensitive assay of methionine synthase activity, based on this principle, is described. PMID- 4036451 TI - High mobility group non-histone chromosomal proteins from chicken thrombocytes and erythrocytes. AB - The high mobility group non-histone chromosomal proteins (HMG) from chicken thrombocytes were compared with those from chicken erythrocytes. In terms of their extractability, electrophoretic behaviour in polyacrylamide gels containing 2.5 M-urea, and amino acid composition, the HMG proteins of these cells were indistinguishable. However, microcomplement fixation assay performed in the presence of antiserum against HMG-1 and HMG-2 revealed that these high molecular weight HMG proteins of chicken thrombocytes and erythrocytes are not cross reactive. Electrophoretic analysis of HMG-1 and HMG-2 from these two types of cells in polyacrylamide gels containing 6.25 M-urea suggested differences in the HMG-2 patterns. PMID- 4036452 TI - Comparison of non-histone proteins from hamster Kirkman-Robbins hepatoma and liver. AB - Three classes of non-histone proteins were obtained from hamster Kirkman-Robbins hepatoma and liver nuclei following separation of nucleic acids with the polyethylene glycol-dextran mixture and fractionation of nuclear proteins on hydroxylapatite in a salt-glycerol-phenylmethylsulphonyl fluoride system at increasing concentrations of Na+ and K+ phosphate buffer, pH 6.8. Two-dimensional polyacrylamide gel electrophoresis of these proteins documented their high heterogeneity; many spots were common but some spots specific only for neoplastic or normal tissue were also observed. PMID- 4036453 TI - Two pools of microsomal phosphatidylethanolamine detected by the use of fluorescamine. PMID- 4036454 TI - Parenchymal operations of the lower pole of the kidney with a double collecting system. AB - The authors present four cases of unilateral kidney with a double collecting system where calculous change has occurred in the lower collecting system. In one of them, marginopolar nephrotomy, while in three, heminephrectomies in the destructed lower segment of the kidney were performed. The remaining upper part functioned perfectly later on. The avoidance of unjustified nephrectomy is stressed. PMID- 4036455 TI - Experimental retroperitoneal infection. AB - A bacterial inoculum was positioned intraperitoneally and retroperitoneally in animals who had been treated with various antibiotic programs. The results indicate that the retroperitoneal tissue is more resistant to severe infectious complications than the general peritoneal cavity. PMID- 4036456 TI - Percutaneous aspiration biopsy in perineal recurrences after abdominoperineal extirpations. AB - The authors recommend the introduction of percutaneous aspiration biopsy--a new method used by them for demonstrating perineal recurrences after abdominoperineal extirpations. The method is fast and easy to perform, simple and can be used for screening. It may be an addition to the therapeutic and diagnostic arsenal. PMID- 4036457 TI - Correlation between the incrustation of intrauterine devices and the duration of their use. AB - The usefulness and side-effects of intrauterine contraceptive devices (IUDs) are evaluated on the basis of various aspects (e. g. effect of postabortal and post partal insertion, expulsion of device, frequency of pregnancies, bleeding and inflammation, etc.) [1, 2, 3, 4]. However, the incrustation of the device has been ignored although the coating on the major part of the surface is easy to study. The rough surface coating is very likely to be associated with some side effects [5]. In our report we have tried to find some links between the degree of incrustation and the duration of using the device. PMID- 4036458 TI - Bilateral urological tumours. AB - In the 5-year period between January 1, 1977 and December 31, 1981, 6 patients with bilateral urological tumours localized in various organs were treated at the Department of Urology, Debrecen University Medical School. As compared to earlier results, the survival of patients with bilateral adrenal renal and testicular tumours may be improved by the early diagnosis, immediate and adequate treatment, by a careful follow-up lasting for years and, when needed, by a delayed intermittent chemotherapy. PMID- 4036459 TI - [Esophageal and gastric fistulas following surgery of the esophagogastric junction]. AB - Seven cases of oesophageal and gastric fistulae after hiatal hernia surgery are reported: 4 fistulae occurred after an abdominal anti-reflux repair; 3 after an intrathoracic Nissen repair. The clinical symptomatology of these complications highly influences their therapeutical strategy. The fistulae with only an abdominal manifestation (subphrenic abscess or peritonitis) are opposed to those with mediastinal or pleural symptoms. The different modalities of treatment and their results are analysed. The authors prefer in case of a fistula with abdominal manifestation a directed fistulization associated with enteral alimentation; in case of a fistulae with thoracic manifestation an oesophageal exclusion with delayed restoration of G.I. tract continuity is indicated. PMID- 4036460 TI - [Colonothoracic fistulas: presentation of 2 cases]. AB - Two cases of colothoracic fistulae are reported. The first one is secondary to pulmonary actinomycosis, the second to complicated colic diverticulitis. The etiologies of colothoracic fistulae are multiple and can be divided in intrathoracic or intraabdominal origin. The treatment includes: effective intravenous antibiotherapy, colic resection of the concerned portion and thoracic drainage. PMID- 4036461 TI - [Digestive fistulas in Crohn's disease]. AB - From 1977 up to 1983, 29 patients were operated upon for Crohn's disease with digestive fistula (dead fistulae, ileocecal and contiguous ileoileal fistulae being excluded). The majority of the fistulae arose from the distal ileum (n = 22). After an average duration of the disease of 7 1/2 years, the patients were admitted for surgical treatment, either electively (group I, n = 19), or in urgency (group II, n = 10). Eleven patients exhibited some signs of malnutrition, 13 needed a total parenteral nutrition for an average of 10 days; one patient had to be operated upon in emergency (hemorrhage and sepsis); the others had a normal bowel preparation. The resection of the diseased bowel at the origin of the fistulae included right ileocolic resections (n = 25), left (n = 1) or total (n = 3) colectomies, with primary anastomosis in all but two cases. The "target bowel" was treated as conservatively as possible: limited small bowel resection, single suture of the gastric, duodenal or sigmoidal walls, and bladder drainage. A segmental resection of the sigmoid colon was realized in 5 cases where a single closure of the wall defect was impossible. There was no postoperative death, no septic complications, and no signs of anastomotic dehiscence. Fistula recurrence "in situ" occurred only once. A spectacular health improvement, with a significant weight gain, was observed in 85% of the cases. Further outcome of the disease remains out of control. PMID- 4036462 TI - [Vesico-intestinal fistulas]. AB - A review is given on frequency, etiology, anatomopathology and physiopathology of vesico-intestinal fistulas. Symptomatology and diagnosis with stress on adjuvant technical investigations are studied. In conclusion the principles for a surgical treatment are discussed. PMID- 4036463 TI - [Postoperative pancreatic fistulas: clinical study of a series of 114 consecutive cephalic duodeno-pancreatectomies]. AB - The present study explores the incidence, the predisposing factors and the consequences of pancreatic fistulae in a series of 114 consecutive, non selected, pancreatico-duodenal resections performed during the period January 1967-December 1982 for malignant and benign diseases of the (peri)ampullary region and the head of the pancreas. Overall hospital mortality reached 10.8% (12/114 pat.). The most common surgical complication was pancreatic fistula (17 pat.-14.9%) responsible for half of the postoperative fatal outcomes. The incidence of the pancreatic fistula is significantly influenced by a patient age of over 65 years, a preoperative serum bilirubin level exceeding 6 mg %, urgent degree of the intervention, presence of a renal insufficiency and last but not least by the poor quality of the pancreatic remnant. As surgical treatment of this complication is compromised by a high mortality (40% - 4/10 pat.), surgery should be reserved to hemorrhagic or persistent local or systemic, septic complications. Therefore more attention should be given to the prevention of this complication by a careful patient selection, based on evaluation of the different mentioned risk factors and by an adequate technique based on a separation of the different anastomoses by the greater omentum and the transverse mesocolon. PMID- 4036464 TI - Sensitive fasciocutaneous flaps with nervus cutaneous femoris lateralis and nervus saphenous. A preparatory study. PMID- 4036465 TI - Sensitive fasciocutaneous flap with nervus saphenous. Preliminary report. PMID- 4036466 TI - Sensitive fasciocutaneous flap with nervus cutaneous femoris lateralis. Preliminary report. PMID- 4036467 TI - Free-transfer omental flap follow-up. An experimental study. PMID- 4036468 TI - Reorganization of the blood circulation after revascularization of microsurgical free grafts. PMID- 4036469 TI - Oligosiloxans in reconstructive surgery of the face. PMID- 4036470 TI - Giant congenital nevus as a basis for the development of malignant melanoma. PMID- 4036471 TI - [The acromioclavicular joint]. PMID- 4036472 TI - [Surgical treatment of epicondylitis of the humeral radius using a modified method]. PMID- 4036474 TI - [Bernbeck's osteotomy in persistent anteversion and valgosity of the femoral neck in congenital hip dysplasia and certain types of Perthes disease]. PMID- 4036473 TI - [Initial experience with Steel's triple pelvic osteotomy]. PMID- 4036476 TI - [Early diagnosis of congenital hip dysplasia in Ostrava 1977-1983]. PMID- 4036475 TI - [Contrast arthrography of the hip joint in children (correlation of the contrast arthrogram with surgical findings in the hip)]. PMID- 4036477 TI - [12 years' experience in the examination of the hip joint in neonates]. PMID- 4036478 TI - [Early prevention of hip joint dysplasia. I. Present state of organization, diagnosis and therapy]. PMID- 4036479 TI - [Disorders of ossification and growth of the proximal end of the femur due to the incorrect use of abduction treatment of luxatio coxae congenita]. PMID- 4036480 TI - [Late results in the therapy of equinovarus deformities of the foot]. PMID- 4036481 TI - [Tuberculous arthritis of the elbow joint--results of resection treatment and arthroplasty after 10 years]. PMID- 4036482 TI - [New aspects of carpal injuries. III. Fractures of the scaphoid bone]. PMID- 4036483 TI - [Treatment of fractures of the femoral diaphysis in childhood]. PMID- 4036484 TI - Influence of acute alcohol intoxication on the outcome of severe non-neurologic trauma. AB - The influence of acute alcohol intoxication on the outcome of severe non neurologic trauma was investigated in a prospective study. Alcohol was found in the blood in 35 of the 69 patients, with mean level 136 +/- 13 mg/100 ml. The patients were admitted to hospital 29.5 +/- 2 min after the injury and had mean ISS 25 +/- 2. In the patients with alcohol in the blood, the blood pressure and PCO2 on arrival were lower than in the other patients. When the alcohol level exceeded 100 mg/100 ml, the blood pressure and PCO2 were lower than in the sober patients despite significantly shorter time between injury and admission to hospital. The hospital stay and mortality were similar in the alcohol and the control group. The greater hypovolemia in the patients with alcohol in the blood indicates that alcohol may be a negative factor for the traumatized patient if resuscitation is delayed, and it underlines the need for rapid and adequate fluid resuscitation of these patients. PMID- 4036485 TI - Painful scars after thoracic and abdominal surgery. AB - Painful scars after thoracic or abdominal surgery were treated in 37 patients with various methods, including analgesic block, transcutaneous nerve stimulation (TNS), neurotomy, scar resection, epidural spinal electrical stimulation and thermocoagulation. At follow-up, three patients were free from pain and three experienced significantly less pain as a result of the treatment. In two other patients the pain had spontaneously diminished. The results indicate that surgery on peripheral structures is not effective, which suggests that the source of the pain is to be found in central structures. The authors advocate conservative measures such as blockade, TNS and physiotherapy in combination with psychologic support. PMID- 4036486 TI - Pancreatic function in patients with hyperparathyroidism. A study with the Lundh test. AB - To elucidate the assumed relationship between hyperparathyroidism and pancreatitis, the pancreatic function was studied in 20 patients with hyperparathyroidism. In all cases removal of a parathyroid adenoma was followed by normalization of preoperative hypercalcemia. A modified Lundh's test with duodenal aspiration was performed before and after the operation. The volume of the aspirate and its content of electrolytes and pancreatic isoamylase were compared with findings in an age-matched control group. Preoperatively the volume of secretion was significantly less in the patients than in the controls. Carbonate levels were also decreased, but changes in enzymatic activity were slight. Postoperatively there was significant increase in aspirate volume and fall in the level of duodenal calcium. The results suggested an influence of hyperparathyroidism on exocrine pancreatic function, even when no symptoms of pancreatic disease are present. PMID- 4036487 TI - A neurophysiologic investigation of thoracic outlet syndrome. AB - Earlier reports have been conflicting as regards the value of neurophysiologic measurements in the diagnosis of thoracic outlet syndrome (TOS), presumably due to differences in selection of patients and in selection and standardization of neurophysiologic tests. The object of the present study was to assess the value of extensive conventional neurophysiologic measurements for the diagnosis of brachial plexus compression in patients with clinical TOS as determined from standardized criteria. The results are discussed in the light of expected neurophysiologic findings at different degrees of brachial plexus compression. PMID- 4036488 TI - Acute nontraumatic extremity ischaemia in Sweden. A one-year survey. AB - An attempt was made to evaluate the results of treatment for acute nontraumatic extremity ischaemia in Sweden during one year. A questionnaire was sent to all surgical units, and 61% replied. Of the total 586 evaluated cases, 497 were classified as embolism and 89 as acute thrombosis. Patient age strongly influenced results in both groups as regards limb salvage and mortality rates. The site of embolic occlusion also influenced mortality, with greatly heightened rate in aortic occlusion. Delay of operation for more than 12 hours after onset of symptoms was associated with increase in amputation rate and mortality. Adequate heparin therapy significantly improved results after embolectomy, but had no such effect after surgical treatment of thrombosis. The amputation rate was higher after acute thrombosis than after embolism. The authors conclude that patient age should be considered in comparisons between different case series of acute ischaemia, that embolus site and time of surgery are important determinants of mortality and amputation rate, and that heparin significantly improves results of embolectomy. PMID- 4036489 TI - Thromboendarterectomy vs. aortic bifurcation graft for unilateral iliac artery atherosclerosis. AB - Retrospective comparison was made of the results from 57 unilateral ilio-femoral thromboendarterectomies in 55 patients and 42 bifurcation grafts in 42 patients. There were three hospital deaths, one after thromboendarterectomy and two after insertion of bifurcation graft. No early or late graft infection occurred. The five-year cumulative patency rate was significantly higher in the bifurcation graft group than after thromboendarterectomy (85% vs. 61%). This higher patency rate supports the concept that local thromboendarterectomy has only limited indications. PMID- 4036490 TI - Intestinal intussusception valve for postgastrectomy bile reflux and/or dumping. AB - The short-term results of a new surgical procedure for prevention of duodenogastric reflux and rapid gastric emptying after partial gastric resection are reported. A jejunal segment provided with an intussusception valve was interposed between the gastric remnant and the duodenum in six patients with severe postgastrectomy symptoms. Duodenogastric reflux, determined with an isotope derivative method, was found to be completely eliminated after the remedial operation. Gastric emptying of a glucose solution showed no significant delay. Previous gastroscopic findings of "gastritis" could not be recognized at postoperative examination. The histologic mucosal changes showed no remission, however. No patient became completely free from gastric symptoms after the remedial operation. The residual symptoms possibly were caused by impaired emptying of the gastric remnant. Gastric mycosis was found occasionally in all the patients during follow-up. The jejunal intussusception valve effectively prevented bile reflux and seemed to have a beneficial effect on dumping symptoms. PMID- 4036491 TI - Neurotensin-like immunoreactivity in plasma after fat intake in normal and obese subjects and after jejunoileal bypass. AB - The plasma concentration of neurotensin-like immunoreactivity (p-NTLI) was measured after oral intake of fat in (a) healthy non-obese volunteers, (b) grossly obese but otherwise healthy persons, and (c) patients who had undergone jejunoileal bypass because of gross obesity. In addition, p-NTLI was measured after intravenous infusion of fat in healthy non-obese volunteers. Basal p-NTLI levels were significantly higher in the patients with bypass than in the obese group. After oral intake of fat, the increase in p-NTLI was much greater and more sustained in the bypass group than in the two other groups. The type of bypass (end-to-end, end-to-side or biliointestinal) and the time after the operation did not correlate with the p-NTLI response. Intravenous infusion of fat evoked no increase in p-NTLI. To produce a rise in p-NTLI level, therefore, the fat does not have to be absorbed and hematogenously distributed to the N-cells (neurotensin-storing cells). This observation may suggest that direct contact between chyme and the N-cells, or local neural or hormonal factors, are required to stimulate release of NTLI. The authors suggest that increase in the postprandial release of neurotensin may promote the diarrhoea after bypass operations, and possibly has other physiologic effects in such patients. PMID- 4036492 TI - Stomach distension in extremely obese and in normal subjects. AB - The maximal tolerable distension of the stomach was measured with a balloon system in 16 extremely obese and 11 normal-weight subjects. The mean maximal tolerated volume was significantly greater in the obese group (1763 +/- 70 vs. 1000 +/- 67 ml). The volume at which a satiety-simulating sensation appeared was likewise greater in the obese group (850 +/- 74 vs. 541 +/- 44 ml). The intragastric pressure originating from the stomach wall as such presumably was similar in both groups. The greater capacity for gastric distension in extremely obese persons may be an etiologic factor in the development of obesity or an adaptation to the eating pattern. PMID- 4036493 TI - Acute epididymitis with abscess formation in an infant. AB - A case of non-specific epididymitis with acute abscess formation in a 3-month-old infant is presented. Excision of the abscess was curative. The need of further examinations in the presence of urological symptoms is emphasized. PMID- 4036494 TI - Oedeme bleu involving the lower limb. AB - Oedeme bleu may masquerade as an acute vascular disorder of the limb. We present a case of this syndrome occurring in a young female with the physical signs involving the lower limb. PMID- 4036495 TI - Repair of ruptured oesophagus. A case report. AB - Oesophageal perforation or rupture is a serious condition. Delayed diagnosis is associated with high mortality rate. A method of repair is described, used to cover a lower oesophageal tear with high gastric fundoplication in three cases with delayed diagnosis (greater than 12 h), two of which survived. PMID- 4036496 TI - Lumbar hernia. AB - Even if it is more than 250 years since the first description of a lumbar hernia occurred in the literature the diagnosis is still rare. This disease is discussed in the light of a case history with a primary lumbar hernia from the Grunfelt Lesshaft triangle. The diagnosis is usually not difficult to establish although certain differential diagnosis has to be considered. The treatment is surgical either as in the present case with a simple closure or when larger defects in the transversalis fascia are present with more extensive surgery. PMID- 4036497 TI - Conservative surgical treatment of splenic cysts. AB - The common treatment of splenic cysts is splenectomy, but with today's knowledge of the important position of the spleen in the infection defense, it is advisable to preserve the spleen whenever this is possible, especially in younger individuals. A large non-parasitic, benign splenic cyst is excised. Postoperative ultrasound control presents a normal appearance of the spleen. PMID- 4036498 TI - Oxygen therapy for pneumatosis coli. Symptomatic and radiologic remission of colonic gas cysts after breathing high-concentration oxygen. AB - Pneumatosis coli in a 72-year-old woman caused severe incapacitation by diarrhoea and faecal incontinence. Treatment consisted of oxygen via a Venturi mask to give arterial oxygen tension c. 32.5 kPa. It was well tolerated and resulted in symptomatic and radiologic cure within 7 days. Knowledge of this treatment and correct diagnosis are important for avoidance of unnecessary surgery. PMID- 4036499 TI - Body temperature elevation, exercise and serum prolactin concentrations. AB - Ten young healthy normal-weight males were studied in four test situations designed to elucidate the relative role of body temperature increase vs that of exercise per se for pituitary hormone release. Tympanic temperature was recorded continuously during the tests. Elevation of body temperature at rest induced by external heating resulted in parallel changes in serum prolactin (Prl), also found when temperature spontaneously returned towards normal. In contrast, temperature elevation of the same magnitude through exercise (450 kpm/min for 40 min) induced no change in Prl secretion. It is concluded that increase in core temperature is a stimulus of Prl secretion and suggested that exercise apparently inhibits the stimulatory effect. PMID- 4036500 TI - Serum reduces the TSH content in rat pituitary cells in culture. AB - Euthyroid rat pituitary cells were plated on a natural extracellular matrix (ECM) and cultured in either a medium supplemented with hormones and growth factors (SM) or in an unsupplemented medium (USM). Hormone supplementation resulted in a marked increase in the number of cells and in a less pronounced increase in the TSH content. Addition of 10% dehormonized serum (DHS) to the medium caused a further increase in the cell number as well as a significant elevation in the GH content but, surprisingly, it caused also a dramatic decrease in the TSH content. Time course experiments revealed that the serum doubled the rate of suppression of the TSH. DHS prepared from rat serum was as effective as that prepared from foetal calf serum and heat-inactivation of the serum did not change its suppressive effect on the production of TSH. This effect was confined to the serum fraction which was precipitable with 45% ammonium sulphate but did not bind to Con-A. It is suggested that a high molecular weight protein fraction of serum reduces the number of thyrotrophs in the culture and/or decreases the rate of TSH production by these cells. PMID- 4036501 TI - Oxytocin determination in steroid producing tissues and in vitro production in ovarian follicles. AB - Immunoreactive oxytocin was measured in ovaries (corpus luteum and follicular fluid) and adrenals of cows, and in testes, seminal vesicles, prostate gland and adrenals of bulls. Secretion of oxytocin was further measured after culture of whole follicles, granulosa cells and theca tissue. Concentrations of oxytocin increased in corpora lutea of cycling cattle until mid-luteal phase (447 +/- 93 ng/g wet weight) and decreased afterwards. Low concentrations were found in corpora lutea of pregnant animals (6 +/- 3 ng/g wet weight). Follicular fluid contains some oxytocin (on average 42-108 pg/ml) but concentrations were significantly higher in the fluid of ovarian cysts (190 pg/ml). After culture of follicles the amount of oxytocin released into the medium increased indicating de novo synthesis. The granulosa cells were the main source of follicular oxytocin. Production increased during luteinization indicating that luteinization is an important step for the production of oxytocin in ovaries. Tissues of testes (65 +/- 10 pg/g wet weight) and adrenals from cows (122 +/- 39 pg/g wet weight) and bulls (111 +/- 2 pg/g wet weight) contained oxytocin but at much lower concentrations compared to corpus luteum tissue. About 10 times higher concentrations of oxytocin were measured in the adrenal medulla (717 +/- 96 pg/g wet weight) compared to the cortex (72 +/- 11 pg/g wet weight). Seminal vesicles and prostate gland contained no measurable amounts of oxytocin (less than 5 pg/g wet weight). PMID- 4036502 TI - Distribution of neurotensin-like immunoreactivity in the hypothalamus, pituitary gland, and gastro-intestinal tract of rats. AB - The distribution of neurotensin-like immunoreactivity (NTLI) in the pituitary gland, hypothalamus, and throughout the gastro-intestinal tract of adult rats was determined by radioimmunoassay (RIA). NTLI concentrations were higher in the hypothalamus than in the pituitary gland or gastro-intestinal tract. The anterior and posterior pituitary gland had almost the same concentration of NTLI. In the gastro-intestinal tract, the mucosal layer of the small intestine had abundant NTLI. The mucosal layer had higher NTLI levels than the muscular layer throughout the alimentary tract. PMID- 4036503 TI - Adaptation to phosphorus depletion: effect of streptozotocin-induced diabetes mellitus. AB - The effect of streptozotocin-induced diabetes mellitus (DM) on the adaptive response to phosphorus depletion (PD) was investigated in order to examine if DM has any influence on the adaptation to PD in rats. PD for 7 days caused a marked reduction in serum phosphate (Pi) levels and increase in serum calcium (Ca) concentrations in control rats. In contrast, the increase in serum Ca concentration caused by PD was almost entirely eliminated in DM rats. Similarly, while bone Ca and P content was decreased by 7 days of PD in control rats, no significant changes in bone mineral contents were observed in DM rats during PD. There was a marked reduction in fractional excretion of Pi and an increase in fractional excretion of Ca during PD in both control and DM rats. Serum somatomedin A levels measured by radioreceptor assay were lower in DM rats compared to those in control rats, but PD caused no significant changes in either group of animals. These results demonstrate that the development of hypercalcaemia and reduction in bone mineral content in response to PD were inhibited while the renal tubular responses to PD were not affected in DM rats. It is suggested that the inhibition of the hypercalcaemic response to PD in DM rats is mainly due to an inhibition of the resorptive response of bone to PD, and that insulin either directly or indirectly may play a permissive role in the development of the resorptive response of bone to PD. PMID- 4036504 TI - Antibodies against animal growth hormones appearing in patients treated with human growth hormone: their specificities and influence on growth velocity. AB - The appearance of anti-human growth hormone (hGH) and anti-non-hGHs antibodies in 27 patients with idiopathic hypopituitarism, treated for periods of 6-18 months with three different preparations of hGH, was investigated. The preparations induced antibodies to GH in 21 out of the 27 patients: 10 patients produced exclusively an anti-non-hGH response, whereas 11 generated both anti-non-hGH and anti-hGH antibodies. The levels of antibodies against hGH had low correlation with decreased growth velocity, whereas those for the antibodies against non-hGHs did not correlate with decreased growth velocity. PMID- 4036505 TI - Surgery depresses pulsatile growth hormone release in rats for up to 2 days. AB - In order to study the pulsatile release of rat growth hormone in a stress-free environment, many investigators obtain sequential blood samples from individual rats bearing an indwelling, right atrial cannula. There has been little systematic study of the stressful effects of the cannulation procedure on the pulsatile release of rat growth hormone. We examined the acute and chronic effects of right atrial cannulation on growth hormone release in male rats by monitoring plasma growth hormone concentration at every 2 min. Right atrial cannulation was performed under ether anaesthesia. Blood was collected from the rats for a 2 h period (11.00-13.00 h), either immediately following, or 2, 3 or 7 days following the surgery. When blood was collected 7 days after surgery, growth hormone was released in large bursts. The amplitude of these bursts however, did not differ significantly from the bursts of growth hormone in rats cannulated 3 days prior to blood collection. On the other hand, the bursts of hormone release in rats cannulated immediately or 2 days before blood collection were significantly smaller in amplitude than those in rats cannulated 3 days before collection, but were not significantly different from each other. In many of the rats cannulated immediately before or 2 days before blood collection, pulsatile growth hormone release was completely suppressed. The results of the study suggest that blood sampling from right atrial cannulae to measure the plasma concentration of rat growth hormone should not be carried out until at least 3 days after the cannulation procedure. PMID- 4036506 TI - Serum thyroglobulin (Tg) stimulation with bovine TSH: a useful test for diagnosis of congenital goitrous hypothyroidism due to defective Tg synthesis. AB - Sixteen patients with congenital goitre were submitted to a bovine TSH stimulation test (bTSH), and serum thyroid hormones (T3, T4), TSH and thyroglobulin (Tg) were measured before and after bTSH injection. In 9 patients with an organification defect basal levels of Tg were normal (19.4 +/- 3.1 micrograms/l) rising after bTSH to a mean level +/- SEM of 37.3 +/- 4.1 micrograms/l. Six patients with defective Tg synthesis or release had a mean basal level of serum Tg of 8.7 +/- 1.9 microgram/l (mean +/- SEM) and failed to raise serum Tg concentrations after bTSH (mean +/- SEM: 10.4 +/- 2.1 micrograms/l). In both groups a modest although significant (P less than 0.05) change in serum thyroid hormones after bTSH was noted. We conclude that the bTSH test may be used to distinguish the group with defective Tg synthesis or release from other types of congenital goitre. PMID- 4036507 TI - Prenatal diagnosis of a thyroglobulin synthesis defect in goats. AB - A strain of goats with congenital goitre due to a thyroglobulin (Tg) synthesis defect was studied. All goats excreted low molecular weight iodinated material (LOMWIOM) in their urine, but non-goitrous goats excreted in the LOMWIOM fraction less than 5 micrograms iodine per 24 h and the goitrous ones more than 15 micrograms iodine per 24 h. Prenatal diagnosis of the Tg synthesis defect in goats is possible since non-goitrous goats pregnant with goitrous kids excrete in the LOMWIOM fraction more than 10 micrograms iodine per 24 h while non-goitrous goats pregnant with non-goitrous kids excrete 10 micrograms or less iodine per 24 h as LOMWIOM. In 24 out of 25 cases a correct diagnosis could be made in the last 47 days of pregnancy. We argue that prenatal diagnosis of analogous defects in man may also be possible, using the excretion of LOMWIOM in maternal urine as yard-stick. By means of field desorption mass spectrometry (FOMS) and high performance liquid chromatography (HPLC) monoiodohistidine was identified as the major component of the LOMWIOM fraction in the urine of goitrous goats. PMID- 4036509 TI - Repercussion of mycoplasmas on male and female sterility. AB - The importance of genital mycoplasmas has been widely discussed since the beginning of 1970 and is still considered as controversial. This paper will attempt to evaluate critically the new information and try to outline current concepts concerning the role of this unique group of microorganisms in involuntary infertility and pregnancy losses. PMID- 4036508 TI - Ontogeny of thyrotrophin concentration in perinatal rats. AB - Negative feedback control by triiodothyronine (T3) of thyrotrophin (TSH) secretion from rat pituitary glands was studied during the perinatal period of rat development. Foetal serum TSH concentration declined significantly between 20 and 21 days of gestation, reached a low level at delivery, and remained low for several days after birth. T3 suppressed serum TSH concentration in a dose responsive manner when given to foetuses on day 20 of gestation at 0.13 to 2.0 micrograms/100 g body weight of the estimated body weight. The responses of serum TSH levels and thyroid weights to PTU treatments differed with gestational age. We conclude that negative feedback control by T3 of serum TSH concentration exists in rat foetuses as early as day 20 of gestation and differs from that found in adult rats. PMID- 4036510 TI - Some molecular features of human cervical mucus. AB - 1) The time preservation effect of the enzymatic activities present in human cervical mucus has been studied. 2) In order to protect the enzymatic activities of the mucus from bacterial impurities, the enzymes studied were assayed in presence of NaN3. 3) The effect of an acid pH likes present in the vagina was also studied: a low pH exerts a marked inhibition on mucus enzymes. 4) the use of nonionic detergents for mucus solubilization does not produce a marked increase of the enzymatic activities studied. 5) A NADP-dependent malate dehydrogenase in peri- and post-ovulatory period has been identified. 6) The presence in mucus of at least four lactate dehydrogenase isoenzymes has been demonstrated and their absolute values determined. PMID- 4036511 TI - In vitro fertilization and embryo transfer programme in Ljubljana. AB - Results of the IVF-ET programme from June 1983 to July 1984 are presented. The procedure was performed in 98 women in 127 cycles. Six normally ongoing clinical pregnancies, three early spontaneous abortions and six biochemical pregnancies were achieved. The laparoscopic techniques of oocyte retrieval were used. Ovulation was first stimulated by clomiphene citrate and later on by gonadotropins only. Comparison of these two regimens showed gonadotropin stimulation to be more effective than clomiphene stimulation, considering the respective transfer rate of 73.3% (gonadotropins) and 18.8% (clomiphene). PMID- 4036512 TI - Endoscopy of the tube (= tuboscopy): its prognostic value for tuboplasties. AB - A tuboscopy was performed during tuboplasties, in 131 cases; this method gives the surgeon a direct, panoramic view of the ampullary mucosa; the lesions observed differ in 50% of cases from what was expected according to the hysterosalpingography. A 2 year follow-up shows that normal uterine pregnancies occurred only in women with at least one tube with normal mucosa according to the tuboscopy, whichever the lesions or the results of the hysterosalpingography; the other cases only had ectopic pregnancies or spontaneous abortions. PMID- 4036513 TI - The value of the postcoital test according to etiology and outcome on infertility. AB - Post coital test (PCT) has been analysed in 150 women divided into 3 groups of 50 patients consulting for infertility. In group I, women achieved pregnancy whereas in group II, women were not pregnant during the same period of observation and had a sterility of non-tubal origin. Group II included women with infertility due to tubal factor. The results of the PCT were not significantly different in group I and in group III. More than 50% of the women had a good PCT (more than 7 motile sperms/hpf). In women of group II, 75% had an inconclusive test (less that 5 sperms/hpf) or negative tests, significantly different from the % observed in group I (44%). Inconclusive PCT in group II were due to anovulatory cycles in 50% of the cases and to cervical infection in 25% of the cases. Status post cauterization of the cervix, anatomical or immunological problems and sexual dysfunctions accounted for the remaining cases. Prognostic significance of the PCT is discussed according to these results. PMID- 4036514 TI - Corpus luteum function assessed by serial serum progesterone measurements after laparoscopic endotherm sterilization. AB - Estimation of serum progesterone as an indication of luteal insufficiency after endotherm sterilization operation in 14 patients is reported. There is a tendency to shortening of the length of the menstrual cycle. This could either be due to a luteal insufficiency or possibly to a shortening of the follicular phase, or both. PMID- 4036515 TI - A possible role of Chlamydia trachomatis as a causative agent in epidydimal infertility. AB - Chlamydia Trachomatis is the most important etiological agent of idiopathic epididymitis in men of 35 years or younger, whereas coliform bacteria are more frequent in older men. The Authors report their findings in a group of eighteen patients investigated in order to establish whether, years after the acute or subclinical infection, arguments could be found to hold Chlamydiae responsible for the origin of epidydimal infertility. PMID- 4036516 TI - Ovarian adhesions impair ovulation. AB - The concentration of progesterone in peritoneal fluid, aspirated from the pouch of Douglas by laparoscopy, 72 hours after the peak of the luteinizing hormone in serum is believed to indicate whether the ovarian follicle has ruptured or not. Twenty six patients were studied. The volume of peritoneal fluid 72 hours after the peak of the luteinizing hormone was markedly decreased when bilateral ovarian adhesions were present. Progesterone concentrations, assayed during the early luteal phase in peritoneal fluid of women with bilateral ovarian adhesions, were significantly lower than in women with a corpus luteum presenting an ovulation stigma and even significantly lower than in those without ovulation stigma (luteinized unruptured follicle syndrome). The assay of progesterone in peritoneal fluid during the early luteal phase may be of value in women with ovarian adhesions. PMID- 4036517 TI - An enzyme-linked immuno sorbent assay for salivary estriol during normal pregnancy. AB - It has been recently demonstrated that the concentration of Estriol in saliva increases in the course of pregnancy, similarly to the plasmatic concentration of unconjugated and total Estriol. As an alternative to RIA, which is an expensive method and requires a highly specialized laboratory, there is now available a competitive, sensitive and rapid enzyme-linked immuno sorbent assay (ELISA) for Estriol in saliva and plasma. Aim of this study is to compare the levels of Estriol concentration, measured by RIA and by ELISA in saliva and plasma in seven women tested every week from the 30th week to the term of pregnancy. PMID- 4036519 TI - [Estimation of prevalence of hematological diseases in Japan]. PMID- 4036518 TI - Antifertility efficacy of Catharanthus roseus Linn: a biochemical and histological study. AB - Oral administration of Catharanthus roseus Linn, leaf extract caused widespread testicular necrosis, hyalinization of tubules and Sertoli cell-only-Syndrome. Biochemical studies revealing notable reduction in glycogen and fructose levels in reproductive tissues support the histological observations and confirm the antifertility properties of C. roseus extract. PMID- 4036520 TI - [An anatomical study on the spleen of archaic fishes. 1. Coelacanthiformes and dipneusti]. PMID- 4036521 TI - [A morphological study of the peripheral and bone marrow lymphocytes in a case of graft-versus-host reaction following blood transfusions]. PMID- 4036522 TI - [Research on the immune status in patients with clonal hemopathy]. PMID- 4036523 TI - [An improved culture method without human plasma for megakaryocyte colony formation: megakaryocyte colony forming cells (CFU-M) in human umbilical cord blood]. PMID- 4036524 TI - [Appearance of monoclonal gammopathy and auto-immune hemolytic anemia following intake of drugs]. PMID- 4036525 TI - [Determination of the free thyroxine concentration (FT4) in serum using the FT4 fraction and total thyroxine concentration]. AB - A new equilibrium assay for the determination of serum free thyroxine was evaluated in 514 patients. The assay comprises a two-vial-procedure to measure total thyroxine and free thyroxine fraction by use of monoclonal antibodies. Free thyroxine concentrations are calculated from fT4-fraction and total thyroxine concentration readings. In euthyroidism the average free thyroxine fraction (%fT4) was 0.011%, in hyperthyroidism this fraction was elevated, in hypothyroidism it was below normal. In patients with TBG anomalies, TBG values were inversely correlated with fT4 fraction readings. The "euthyroid reference range" of FT4 (SPAC ET) was between 0.70 to 1.78 ng/dl. This euthyroid range of FT4 was determined from TT4 concentrations measured by T4-RIA (SPAC T4 MONO) which were 30% above TT4 values measured by conventional T4-RIA (SPAC T4 POLY; polyclonal antibodies). However, a different euthyroid range of FT4 between 0.55 to 1.30 ng/dl was observed as well as by other investigators when conventional T4 RIA measurements were used for calculation of FT4 values. Our results indicate that calculated FT4 concentration values are highly dependent on the methods used for determination of total thyroxine concentrations. Precision and reproducibility of this two vial equilibrium assay did not meet the requirements mandatory for the application as a clinical routine diagnostic procedure, and its general use for this purpose can as yet not be recommended. PMID- 4036526 TI - [Diastolic compression of the right atrium and right ventricle as an echocardiographic sign of pericardial tamponade. Case report]. AB - A 33 years old female patient requiring regular hemodialysis for chronic renal failure exhibited a severe hypotensive episode. 2-dimensional echocardiography enabled rapid recognition of the underlying cause. 2-dimensional echocardiography revealed a large pericardial effusion and from the apical window a marked diastolic compression of the right atrium and the right ventricle was noted. These findings have been previously described to be specific for cardiac tamponade. After removal of 400 ml of fluid by pericardiocentesis the clinical symptoms rapidly improved and in the 2-dimensional echocardiography diastolic compression of the right sided heart chambers was not longer evident, although a substantial amount of pericardial fluid was still present. This case report underlines the clinical usefulness of 2-dimensional echocardiography for the diagnosis of cardiac tamponade. PMID- 4036527 TI - Higher nervous activity. Abstracts. PMID- 4036528 TI - Psychometric analysis of behavior pattern A in the Spanish population and its relationship with personality variables. AB - As a first step in the epidemiological study for CHD prevention among the Spanish population, the authors have analyzed two of the instruments for the assessment of the behavior pattern A (JAS and Bortner questionnaires). From a student sample (n = 302), a factor analysis of items and scales was made, relating pattern A scores to Eysenck's personality variables (EPQ). The importance of an accurate psychometric study of pattern A was emphasized, in order to select A subjects as specifically as possible. PMID- 4036529 TI - EEG patterns suggestive of shifted levels of excitation effected by hathayogic exercises. AB - Concurrent with the performance of hathayogic exercises such as Nauli, Bhastrika and Suryabhedana, three characteristic EEG patterns were identified: a "wicket" rhythm at a frequency wave of 12 to 17 Hz, recordable from para-Rolandic areas, which we have called Xi rhythm; a 26-33 Hz sinusoidal activity, confined to the mid-sagittal parietooccipital region; and paroxysmal activity localized in the lateral boundaries of parieto-temporo-occipital regions, bilaterally. - The expectation that hathayogic exercises would affect the electrical activity of circumscribed, relatively well defined areas of the brain was based on the fact that these exercises imply a strong stimulation of somatic and splanchnic receptors, the afferent impulses of which are fed into specific cortical representation areas localized for the most part around central and anterior parietal areas. PMID- 4036530 TI - The Stroop effect on Slovak-Hungarian bilinguists. AB - We studied the processes of interference vs language automatisms in a group of Slovak-Hungarian bilinguists (N = 19, age 13 years) and compared their performance in the Stroop test with two control groups - Slovak (N = 24) and Hungarian (N = 31) monolinguists of the same age. - The Stroop effect, whose essence is an interfering effect of the meaning of the word on its physical characteristic - colour, proved to be a suitable method in the study of information processing in the semantic memory of bilinguists as well as in determining dominance of one language over the other. Slovak-Hungarian bilinguists showed, as a rule, shorter times in Hungarian and approximated in their performance Hungarian monolinguists. It can be assumed that reaction times in the Stroop test are conditioned not only by interference of the other language but also by language automatisms, whereby interference and speech automatisms are in an indirect correlation. - The results thus indicate that processes of interference and language automatisms cannot be separated. Dominance of one language structure over the other (Hungarian over Slovak) was confirmed not only in our experimental method but also in the subjective rating. PMID- 4036531 TI - Undiagnosed phaeochromocytoma in the perioperative period. Case reports. AB - Phaeochromocytomas appear as frequently as one in 1000-2000 patients. Release of catecholamines may be triggered by events in the perioperative period. Patients whose phaeochromocytomas are diagnosed in this period, have a mortality of about 80%. Three patients with perioperative debut of symptoms of a phaeochromocytoma are presented. A possible drug-induced release of catecholamines from the tumour is suggested for two of the patients. The first symptoms of a phaeochromocytoma may be arrhythmias and shock, which favours the use of adrenergic blockade prior to elective removal of phaeochromocytomas. Therapeutic approaches to the treatment of catecholamine-induced heart failure may be potassium and magnesium supplements and possibly drugs reducing circulating angiotensin II activities. Caution is advised in the use of digitalis. PMID- 4036532 TI - The pharmacokinetics of methohexital in young and elderly subjects. AB - The pharmacokinetics of methohexital were investigated in ten young adult volunteers and in seven young and seven elderly patients. The latter two groups underwent enflurane and nitrous oxide anesthesia and surgery. Each subject received a bolus dose of 2 mg/kg of methohexital intravenously. Plasma levels of the drug were measured for 8 h after injection by gas chromatography using a nitrogen detector. Anesthesia (combined with surgery) and increase in age did not separately affect the kinetics of the drug; however, the elimination half-life was longer in the elderly patients group than in the young non-anesthetized volunteers. PMID- 4036533 TI - Etomidate infusion and adrenocortical function. A study in elective surgery. AB - The adrenocortical response to a short tetracosactrin (Synacthen) test was studied in 11 patients receiving either etomidate infusion or thiopentone infusion used to maintain anaesthesia for abdominal hysterectomy. Pethidine was used as the narcotic component. The results showed that etomidate infusion (median 28.5 ug/kg/min) completely blocked the adrenocortical response to corticotropin stimulation for at least 24 h after surgery. No suppression was found in patients receiving thiopentone infusion. It is concluded that etomidate cannot be recommended for routine induction and maintenance of anaesthesia. PMID- 4036534 TI - Enflurane hepatitis. A report of a case with a previous history of halothane hepatitis. AB - "Enflurane hepatitis" has only recently been accepted as a disease entity. As far as the authors know, this paper is the first report on enflurane hepatitis in a patient with a previous history of halothane hepatitis. Our conclusion is that a potent halogenated inhalation agent should never be given to a patient if a prior administration of another such agent has led to the development of hepatic injury. PMID- 4036535 TI - Circulatory effects of haemorrhage during sodium nitroprusside induced hypotension. A study in the rat. AB - The haemodynamic changes induced by acute moderate blood loss were investigated in rats during normotensive halothane anaesthesia and during sodium-nitroprusside induced hypotensive anaesthesia, respectively. Following haemorrhage in the normotensive group, mean arterial blood pressure, heart rate and left cardiac work decreased. Cardiac output was reduced non-significantly. Blood flow was redistributed to favour cerebral, coronary, renal and hepatic circulation, mainly at the expense of blood flow to the carcass. Following haemorrhage in the hypotensive group, cardiac output increased significantly. Mean arterial pressure, heart rate and left cardiac work were unchanged. Absolute values for cerebral, coronary, renal and hepatic blood flow were maintained or even increased, while blood flow to the carcass was unchanged. PMID- 4036536 TI - Does dopamine suppress stress-induced intestinal and renal vasoconstriction? AB - Dopamine interference with intestinal and renal sympathetic reflex vasoconstrictor responses was studied in cats anaesthetized with diazepam, fentanyl and nitrous oxide. Vasoconstriction was induced by electric stimulation of the hypothalamic defence-alarm area and by stimulation of somatic and visceral afferents. In addition, intestinal vasoconstriction was elicited by direct stimulation of postganglionic sympathetic efferent nerves. In the intestine, dopamine administration (7.5 microgram X kg-1 X min-1) was not associated with an attenuation of the investigated sympathetic vasoconstrictor responses, although dopamine per se decreased intestinal vascular resistance by 36 +/- 4%. Due to this dopamine-induced background vasodilation, the intestinal blood flow level during stimulation procedures and concomitant dopamine infusion was higher than during similar stimulations prior to dopamine (for defence-alarm area stimulation 45 +/- 16%, for afferent nerve stimulation 79 +/- 22% and for efferent postganglionic nerve stimulation 66 +/- 16%). In the kidney, dopamine per se had only minor effects on vascular resistance and on changes in vascular tone elicited by the stimulation procedures. The renal blood flow level in response to the stimulation procedures was not significantly affected by dopamine. In conclusion, dopamine may contribute to a sustained intestinal blood flow level when administered during supervening stress-related sympathetic activation. PMID- 4036537 TI - Sciatic nerve block: a new lateral approach. AB - The currently available methods for local anaesthetic block of the sciatic nerve are difficult to perform. Here we describe a new and easier technique for the block. The sciatic nerve is approached from the lateral side of the thigh with the patient lying supine and is identified by simple anatomical landmarks with the help of a nerve stimulator. The technique was found to be safe and effective in over 100 cases. It can be learnt quickly and is easily remembered. PMID- 4036538 TI - Multiple intercostal blocks by a single injection? A clinical and radiological investigation. AB - Three different techniques for producing multiple intercostal nerve blocks using bupivacaine were compared in volunteers. The techniques used were multiple injections at intercostal nerves 7-11, or a single injection employing a needle or a catheter inserted in the 9th intercostal space. The injections were made at the costal angle. The anatomical spread of a mixture of a local anaesthetic and a radio-opaque fluid following the single injection technique at the ninth intercostal space or at the subcostal space was evaluated by computerized x-ray tomography (CT). The distribution of cutaneous analgesia/hypalgesia following all techniques was evaluated by pin prick. No spread of the local anaesthetic to adjacent intercostal spaces or to the paravertebral space could be shown by CT. The distribution of cutaneous analgesia was limited to three segments or less following a single injection. No difference in blood levels of bupivacaine could be found. It is concluded that the single injection technique of producing multiple intercostal nerve blocks is inferior to the multiple injection technique. PMID- 4036539 TI - Comparison of pharmacokinetic and pharmacodynamic parameters following oral or intramuscular atropine in children. Atropine overdose in two small children. AB - Pharmacokinetic and pharmacodynamic parameters of atropine 0.03 mg/kg p.o. or 0.02 mg/kg i.m. were compared in a double-blind study in 20 children with a mean age of 5.1 years undergoing otolaryngological surgery, mostly adenotomy. Outside the study protocol, two small children accidentally received an overdose of atropine 0.3 mg/kg p.o. In addition to atropine, all children received triclofos 70 mg/kg p.o. Following p.o. administration of atropine, the mean maximum serum concentration of 6.7 nmol/l occurred at 2 h. The corresponding result after i.m. administration was 5.7 nmol/l at 0.5 h. Serum concentrations of atropine were 3.5 and 1.3 nmol/l 8 h after p.o. and i.m. administration, respectively. At 70 min the anti-sialogogue effect was clinically satisfactory after both modes of administration. The heart rate increased statistically significantly only after i.m. administration. The mean maximum rise in the rectal temperature before the start of anaesthesia occurred at 1 h and was 0.5 degrees C in the p.o. group and 0.7 degrees C in the i.m. group. The flush phenomenon, mostly on the face and sometimes also on the chest, occurred in both groups, being more intense in the i.m. group than in the p.o. group. The children who developed flush had a statistically significantly higher rise in rectal temperature than the children without flush. There was a positive but weak correlation between the serum concentration of atropine and the heart rate, whereas the correlation between the serum concentration after i.m. atropine and the rectal temperature was weakly negative. On the basis of the present study, there were no decisive differences between the effects and side-effects of the two modes of administration of atropine.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4036540 TI - Hemodynamics and oxygen transport after partial and total blood exchange with pyridoxalated polyhemoglobin in dogs. AB - The effects of a pyridoxalated polyhemoglobin solution (SFH-PLP)n-solution) on cardiovascular hemodynamics and oxygen transport were investigated in a model of partial and total blood exchange in seven dogs. Cardiac output, mean arterial pressure and heart rate were essentially unchanged, even after total blood exchange, due to the long plasma half-disappearance time of (SFH-PLP)n (36 h) and due to the addition of albumin to the solution. The oxygen-binding capacity of (SFH-PLP)n was 1.1 to 1.2 ml O2/g hb. Oxygen availability was reduced to about 50%, resulting from the low hemoglobin concentration and the decreased oxygen binding capacity of (SFH-PLP)n. Since cardiac output did not increase, O2 consumption was maintained by an increase in O2-extraction from 21 to about 50%. However the decrease in mixed venous PO2 to values not below 30 mmHg (4.00 kPa) proves the sufficient unloading capacity of (SFH-PLP)n. The adequate tissue oxygenation of (SFH-PLP)n could be demonstrated by the lack of a metabolic acidosis, the essentially unchanged PO2-histograms of the skeletal muscle and the only moderate decrease in mixed venous PO2. Four dogs survived for more than 3 days; three of them were long-term survivors. This suggests that oxygen supply was maintained by (SFH-PLP)n until red blood cells were restored. PMID- 4036541 TI - Fistula formation following epidural catheter. A case report. AB - A case of fistula formation following epidural catheterisation is presented. The diagnosis and treatment of epidural abscesses are discussed. PMID- 4036542 TI - Ultrarapid induction. AB - We report 250 rapid induction anesthesias performed for the purpose of preventing regurgitation and vomiting in patients with full stomach. The anesthetic technique includes administration of morphine 20 mg and droperidol 5 mg intravenously 10-15 minutes before induction, a voluntary air hyperventilation at the anesthetist's command, during which induction drugs are introduced and an induction with a mixture containing suxamethonium 2 mg/kg and thiopentone 1.4 mg/kg, administered within 1-2 seconds. Eighteen seconds after the onset of injection the loss of lid reflex is observed followed 7 seconds later by masseter muscle relaxation. Within the following 5-10 seconds intubation is carried out in full fasciculation process, before cardia relaxation. With this technique, a mean intubation time of 35 seconds is achieved. The interval of maximum regurgitation risk is lowered to 15 seconds, so that ventilation by mask and cricoid pressure are no more necessary. The technique is indicated in the young and vigorous adult and contraindicated in the old and tainted patient, in coronary patients, in those with low heart output and slowing of circulation. PMID- 4036543 TI - Effect of nitrous oxide on serum vitamin-B12 levels under surgical anesthesia. AB - To evaluate the effect of nitrous oxide (66%) as used in surgical anesthesia on serum vitamin-B12 levels, 27 patients were studied undergoing operations longer than 2 hours. In addition a group of 10 patients was given oxygen/halothane for comparison. In patients receiving nitrous oxide, serum-B12 concentrations showed significant reductions during anesthesia, but increased at the 24th hour and recovered completely at the 72nd hour postoperatively. No significant changes were seen in vitamin levels during and after anesthesia in patients not receiving nitrous oxide. There was also no macrocytosis or hypersegmentation of neutrophils on blood slides taken concomitantly with blood samples in both groups. In view of the rapid recovery of vitamin levels and the fact that, in spite of the significant reductions caused by nitrous oxide none of the individual values decreased below normal, it is suggested that the effect of nitrous oxide as used in surgical anesthesia may be considered insignificant in patients with normal vitamin-B12 values. PMID- 4036544 TI - Photoreceptor nuclei outside of the limiting membrane in the chick retina. AB - The present work describes the presence of some photoreceptor nuclei in the embryonic and adult chick retina which are situated outside of the external limiting membrane. We also discuss their possible degenerative character. PMID- 4036545 TI - Effects of progesterone on nuclear ribonucleoprotein constituents of endometrial cells of the rat. AB - The effects of changes of progesterone concentration on 3H-uridine incorporation and on the volume or number of nuclear ribonucleoprotein particles of the rat endometrial epithelial cells are studied in vivo and in vitro. All progesterone treatments are carried out after estradiol priming and their results are compared with estradiol-treated controls sampled from the same uterus or the same pool of isolated cells. Progesterone induces the same changes, in the parameters studied, administered in vivo or in vitro. Nuclear volume undergoes small but significant increases between 1/2 and 8 h of treatment. The total number of extranucleolar ribonucleoprotein structures as well as the incorporation of 3H-uridine on non nucleolar areas are also increased by progesterone treatments. However, the numerical density of perichromatin granules does not change during these experiments. The nucleolar volume and the incorporation of 3H-uridine in this structure are increased after an early diminution. These results indicate that progesterone induces small increases in the rate of transcription in the nucleolus and in non-nucleolar genes. The constancy of the density of perichromatin granules suggests that progesterone, in contrast to estradiol, does not affect the ratio transcription/transportation of RNA to the cytoplasm. PMID- 4036546 TI - Effects of aminoglutethimide on ovarian histology in the rat. AB - Aminoglutethimide, a corticosteroid inhibitor, administered at a daily dose of 150 mg per kg body weight, showed a dramatic interference with ovarian histology in the rat. The drug caused thinning of the germinal epithelium and disruption of the layers of the follicular cells. It also resulted in the appearance of cytoplasmic vacuoles and distortion of follicle cell nuclei. In the corpus luteum, it caused shrinkage of the lutein cells, resulting in large spaces between the cords of cells. It also arrested immature follicles at various stages of their development. Our results indicate that aminoglutethimide, by modifying ovarian structure in the rat, interferes with the ovulation process. PMID- 4036547 TI - Comparative development of thoracic intervertebral discs and intra-articular ligaments in the human, monkey, mouse, and cat. AB - Developmental features of thoracic intervertrebral discs and their association in the adult with other vertebral structures were investigated in four species. The human anulus fibrosus, nucleus pulposus, and intra-articular ligaments were compared to those of the fetal rhesus monkey, mouse, and kitten. Photomicrographs of transverse sections of intervertebral discs document the presence of intra articular ligaments in fetuses of these four species. Both transverse and sagittal sections of kittens were used to identify the intercapital ligament as it differentiated from the dorsal part of the intra-articular ligament. Relatively frequent dorsal herniation of the thoracic nucleus pulposus in humans may be due to the vestigial nature of the human intra-articular ligament. Quadrupeds have well-developed intra-articular ligaments, which explains anatomically the paucity of dorsal protrusions of the nucleus pulposus into the vertebral canal in the thoracic region of the cat and mouse when compared to the human. The intra-articular ligament was closely associated with the developing prenatal mammalian intervertebral disc in the four species studied, and this relationship and its surgical importance are described. PMID- 4036548 TI - Vasculogenesis in the chick embryo optic tectum. AB - The initial formation and further development of the intraneural blood vessel network in the tectum opticum of the chick from the 4th to the 14th incubation day have been analyzed and some quantitative data morphometrically recorded. Vessels have been filled by intracardial injection of India ink in vivo. As inferred from our previous investigations on the vasculogenesis of several districts of the central and peripheral nervous system in the chick embryo, also in the developing optic tectum growth and distribution pattern of the vessels seem to unfold step by step under the local influence of earlier occurring morpho histogenetic processes of the corresponding neural substratum. PMID- 4036549 TI - A peculiar arteriovenous leptomeningeal complex in the guinea pig. AB - In most areas of the body, arteries and veins run close together, often sharing a common connective tissue sheath. One exception to this is observed in the brain, where arteries come in from the base and veins collect over the convexity. Classically the larger blood vessels are formed by three coats: intima, media, and adventitia. Leptomeningeal vessels are further reinforced by a monolayer of pial cells. In the guinea pig, however, above the corpus callosum we found a group of blood vessels (an artery and several veins) enclosed in a common leptomeningeal sheath. The artery arises at the confluence of the anterior cerebral arteries; the veins drain into the straight sinus. The epithelial nature of the sheath is evident by the close apposition of cell membranes, the presence of junctional devices, and the existence of a basal lamina. The ultrastructural features of this epithelium are similar to those of the arachnoid-dural membrane. Whether this peculiar vascular complex has any specific function needs to be investigated further. The presence of these vessels apparently 'isolated' within a leptomeningeal subcompartment may provide a suitable model to study vascular extravascular-cerebrospinal fluid substance exchange. PMID- 4036550 TI - Solid cell nests of the thyroid. An anatomical survey and immunohistochemical study for the presence of thyroglobulin. AB - A systematic anatomical study of 100 adult human thyroids from autopsies was undertaken for the presence of solid cell nests (SCN). SCN were mainly located in the middle third, with a slight tendency to the upper third, of the lateral thyroid lobes, and placed along a central to paracentral and slightly dorsal longitudinal axis. Immunohistochemical studies for thyroglobulin revealed positive staining in follicular cells connected to SCN and, occasionally, in isolated cells lying within solid clusters from SCN. The anatomical position SCN showed in the present survey is comparable to that shown by the ultimobranchial body (UB) vestiges of human fetuses. The presence of thyroglobulin-positive cells within solid clusters, together with the existence of follicular cells connected to SCN, suggest that SCN may also be a probable source of follicular epithelium as occurs with the UB of some mammals. PMID- 4036551 TI - Partial purification and some properties of tryptophan decarboxylase from a Bacillus strain. AB - Bacteria of different origin were screened for tryptophan decarboxylase activity. The best producer belonged to an unidentified taxonomic entity of the genus Bacillus. In complete medium it produced tryptamine from tryptophan. The decarboxylase could partially be purified from the cells by sonication and DEAE cellulose chromatography. The enzyme had an Mr of 150 000 and a pH optimum of about 7, was stable up to 37 degrees C, and its Km was about 0.3 mM for tryptophan. The enzyme needed pyridoxal phosphate for maximum activity. PMID- 4036552 TI - Early diagnosis of glaucoma. The value of successive stereophotography of the optic disc. AB - A group of 46 patients with ocular hypertension (initial pressure 22-30 mmHg) have been followed prospectively for 5-7.5 years, with special emphasis on optic disc changes. A stereophoto of the disc was taken at each consultation. So far, 24 patients have been put on anti-glaucoma therapy. A slight increase in disc cupping revealed by stereophoto was the first pathological finding in 19 patients. Only one patient developed a field defect without visible disc changes. Neither disc description, cup/disc ratio measurement nor disc drawing were accurate enough to disclose small changes in the cup size. Considerably more patients in the treatment group had a pressure rise of 5 mm or more and repeated intraocular pressures of 30 mm or more during the observation. Stereophotography of the optic disc was found to be a valuable method in the diagnosis of early glaucoma. PMID- 4036553 TI - Epithelial healing: quantitative monitoring of the cornea following alkali burn. AB - A micropolarographic system was used as a quantitative means of monitoring the healing course of corneal epithelium following a 10 second exposure to 0.20 N sodium hydroxide solution. Concentrations of less than that strength produced inconsistent flux baselines due to incomplete damage to the epithelium, while higher concentrations commonly involved the stroma as well. Virtually complete epithelial destruction (down to the basement membrane) and reproducible flux baselines were found, however, with the 0.20 N induced lesion studied in detail here. The healing course following those exposures consisted of two well defined phases: an initial period of hypoflux lasting some 48 h before rising back up to the pre-lesion baseline, followed then by a period of hyperflux lasting about 7 days before decreasing once again down to the pre-lesion baseline. This oxygen flux sequence closely parallels certain sliding and mitotic phases of epithelial healing already established in the literature. PMID- 4036554 TI - Photographic screening for strabismus among mentally retarded children. AB - The prevalence of squint among mentally retarded children is much higher than in the general population. A photographic screening method based on the positioning of the 1st and 4th Purkinje image was applied to 80 mentally retarded children. The method was validated against orthoptic examination of the children. Totally 320 exposures were taken. Fourth Purkinje image was visible on 73% of these. Five children were not evaluable from the 4th Purkinje image. The photographic technique was simple and easy to handle, but comparison between the clinical and photographic diagnoses were inconsistent in 12 out of 80 cases, which made the method unreliable. In some cases the clinical assessments also varied from time to time. A combination of clinical orthoptic assessment and the photographic method is suggested. PMID- 4036555 TI - Lens thickness in western Nigeria. A comparative ultrasonic study in Negros and Danes. AB - A comparative ultrasonic, oculometric study was performed in negroes, West Nigeria (151 persons) and in caucasians, Denmark (88 persons). The negros have thinner lenses than caucasians, and overall ethnic difference of 0.12 mm was found. Male negroes have longer vitreous and axial lengths than male caucasians (VB 0.56 mm, AxL 0.30 mm). PMID- 4036556 TI - Senile cataract and ascorbic acid loading. AB - Serum, aqueous humour, and lens ascorbic acid levels were determined by high performance liquid chromatography in cataract-, closed-angle glaucoma-, and aphakic patients. The total number of 108 patients were subdivided into different groups. In several groups the pre-operative serum and aqueous amounts were tested, whereafter patients in some groups were loaded with ascorbic acid orally. Finally, a second test was performed on samples taken during operation. It turned out that the ascorbic acid concentration mechanism in cataractous eyes needed more than 12 h for maximum reaction on the loading stimulus. The slow reaction is surprising compared to other species, and it may reflect an affection of the secretory process itself in this disease. PMID- 4036557 TI - Regional variation in indications for cataract surgery? An analysis of the pre IOL period. AB - A comparison of indications for cataract surgery in 3 major clinics was done. These clinics serve the population of 3 Danish counties for which the standard operation ratio previously has been shown to be below average, average and above average. Evaluated on basis of pre-operative visual acuity in both eyes, no differences in the indications were found between the 3 clinics. Other possible determinants of rate variation might be differences in doctors' and patients' attitude towards cataract treatment, variation in cataract prevalence and in ophthalmic service supply. PMID- 4036558 TI - Intraocular pressure in the first days after implantation of the semiflexible McGhan/3 M, style 70, anterior chamber lens. AB - Intracapsular cataract extraction employing a corneal incision and with implantation of the semiflexible McGhan/3 M, style 70, anterior chamber lens was performed in a group of 25 patients with senile cataract. Intraocular pressure (IOP) was measured prior to and daily in the first 4 days after the operation. IOP was slightly, but significantly (P less than or equal to 0.05) lower in the observed post-operative period as compared to the pre-operative measurement. Similar results have previously been found after cataract extraction with an identical technique, but without lens implantation. This probably means that early post-operative intraocular homeostasis with respect to IOP is unaffected by the implantation of this type of lens. The fine regulation of early post operative IOP is probably related to the fact that the described surgical technique usually is associated with only minor gonioscopically visible changes of the trabecular meshwork. PMID- 4036559 TI - Binocular interaction in the VEP to grating stimulation. II. Spatial frequency effects. AB - The size specificity of the binocular interaction in the VEP was investigated. VEPs elicited by sine wave gratings were recorded on 3 subjects, with the exception of one experiment where 6 subjects were tested. The recording technique made it possible to obtain responses from each eye, even during binocular stimulation. The VEP amplitude for each eye during monocular stimulation was compared with the response of the same eye during binocular stimulation. A low binocular/monocular ratio indicated a high binocular interaction. When each eye was stimulated by the same spatial frequency, the binocular interaction was highest in the spatial frequency band of 2-4 c/d. When each eye was stimulated by a different spatial frequency, the binocular interaction decreased as the frequencies were made progressively more unequal. The bandwidth at half amplitude was about 1 octave around the center frequency. PMID- 4036560 TI - Fluorescein angiography in homozygote and carrier state of progressive retinal atrophy of the poodle; comparative aspects with human retinitis pigmentosa. AB - Fluorescein angiographic findings in 7 carriers and 7 homozygotes of a recessively inherited disease, generalized progressive retinal atrophy of the poodle, are described in detail and comparisons with 24 healthy control poodles are presented. Two angiographic types of the disease could be distinguished. These are: Type 1, a diffuse, widespread choriocapillaris atrophy associated with retinal vascular and depigmentation changes and Type 2, a predominantly retinal involvement combined with focal choroidal atrophic patches lineating major vessels. These findings share similarities with the observations made of the human disease, retinitis pigmentosa. Unaffected carriers of the disease showed characteristic fundus changes in angiography: patchy, hyperfluorescent depigmentation changes and often minor narrowing and irregularities of the arterioles and poorly visible capillary bed. PMID- 4036561 TI - The normal fundus fluorescein angiogram. II. A longitudinal fluorescein angiographic study of the fundus in clinically healthy subjects without ophthalmoscopically abnormalities. AB - Three consecutive photographic fundus examinations using colour, interference filter photographs and fluorescein angiography showed no intraindividual variation within one year, but a considerable interindividual variation of the morphologic fundus elements was found in 48 eyes of 48 clinically healthy middle aged subjects. There were 20 eyes with distinctly outlined minute hyperfluorescent elements, 15 eyes with minute indistinctly outlined and 3 eyes with distinctly outlined hypofluorescent elements. These elements remained unchanged after one year. In 80% of the eyes with hypofluorescent elements there were characteristically no concomitant hyperfluorescent elements. Seventeen of 48 eyes had fundus elements exclusively visible in the colour and filter pictures. Most hyperfluorescent elements corresponded with elements in the green interference filter photographs (85% of the eyes). These findings indicate minute changes in the layers of Bruch's membrane and the retinal pigment epithelium in most of the eyes. The indistinctly outlined hypofluorescent elements might represent minute choroidal vascular filling defects or minute areas with blockage of the choroidal fluorescence. PMID- 4036562 TI - The normal fundus fluorescein angiogram. III. A longitudinal fluorescein angiographic study of the fundus in insulin dependent diabetics without ophthalmoscopically abnormalities. AB - In 17 insulin dependent diabetics with an apparently normal ophthalmoscopy at the entry of the study, there was a) an individual variation regarding observed fundus elements and b) an intraindividual variation during the observation time of one year, as evident from fundus fluorescein angiography, colour photography and red free filter photography. The examinations were performed on one eye in each subject three times within one year. Hyperfluorescent elements--varying in number from 1 to 5--were found totally in 14 eyes (= 82%). In 6 eyes (= 35%) the number of minute hyperfluorescent fundus elements varied during one year. Hypofluorescent elements were present in 14 eyes (12 eyes with indistinctly and and 2 with distinctly outlined elements) and showed no variation during one year. Eleven eyes (65%) had minute elements--varying in number from 1 to 7--in the colour and red free filter photographs not visualized in the angiograms. After one year 8 red elements were found in 5 eyes, 6 with and 2 without fluorescence. The remaining fluorescent and non-fluorescent elements, constantly present, appeared as minute yellowish spots (n = 37). PMID- 4036563 TI - Diabetic retinopathy after one year of improved metabolic control obtained by continuous subcutaneous insulin infusion (CSII). AB - Twenty-four insulin dependent juvenile diabetics, with no or minimal background retinopathy, were randomly allocated to conventional insulin therapy (CIT) or continuous subcutaneous insulin infusion (CSII) administrated by means of a portable pump. The metabolic control was significantly improved in the CSII group as compared to the CIT group. After one year, a progression of diabetic retinopathy (criterion: development of more than 2 microaneurysms) was observed in 3 of 12 patients in the CSII group and in 4 of 12 patients in the CIT group (P greater than 0.05). A tendency to more severe progression was observed in the CIT group. None developed soft exudates or retinal proliferations. Although no significant beneficial effect of pump treatment could be demonstrated, it seems safe to conclude that pump treatment does not accelerate progression of diabetic retinopathy in patients with no or minimal background retinopathy. PMID- 4036564 TI - Topography of scleral emissaries and sclera-perforating blood vessels. AB - One hundred persons have been subjected to slit-lamp examination for scleral emissaries. The number registered per subject averaged 12.2. Such were most frequent superiorly at 12 o'clock and inferiorly at 6 o'clock, rarer nasally and the rarest temporally. The courses of the perforating blood vessels were equally often radial (30%), incyclo-directed (28%), and excylodirected (29%), whereas rarely parallel with the limbus corneae (10%), and even more rarely irregularly winding (3%). Episcleral pigmentation in relation to emissaries was most frequently observed superiorly and where the vessels ran radial and limbus parallel courses, whereas rarely nasally and temporally and at excyclo-directed and winding courses. PMID- 4036565 TI - Ocular effects of oral lithium in humans. AB - Thirteen healthy adult subjects, 34.2 +/- 7.4 years of age received oral lithium carbonate, 900 or 1200 mg daily for 10 days. Refraction, visual acuity, visual fields, corneal sensation, basal tear secretion, ocular motility, convergence amplitude, near point of convergence, Hertel exophthalmometry, pupillary reflexes, intraocular pressure, voluntary and pilocarpine-induced accommodation, and biomicroscopy and ophthalmoscopy of the anterior and posterior ocular segments were determined 4 days prior to starting lithium, 10 days after commencing lithium, and 14 days after discontinuing lithium. Some subjective visual or ocular complaints were reported, but no clinically or statistically significant change occurred in any parameter studied. There were slight, non significant tendencies toward constriction of the measured visual field, reduction of voluntary and pilocarpine-induced accommodation, and reduction of near convergence amplitude while taking lithium; the former two were reversed when lithium was discontinued, the latter was not. PMID- 4036566 TI - Scanning electron microscopy of normal human corneal epithelium obtained by scraping-off in vivo. AB - The surface of normal human corneal epithelium was examined by scanning electron microscopy (SEM). The study was carried out on specimens obtained by scraping-off in vivo, and immediately fixed. Four different types of microprojections were observed on the epithelial surface: microridges, microvilli, tufted microvilli and knobs. Detailed high magnification of surface microprojections showed that they consist of subunits. Our data suggest a correlation between surface morphology and maturity of the corneal epithelial cell. An evolutive sequence is proposed, from the youngest cell, provided with microridges, to the oldest exfoliating one, with knobs. PMID- 4036567 TI - The femoral head--dead or alive! PMID- 4036568 TI - Hyperpressure in juvenile hip disease. AB - Intra-articular pressure was measured in 94 hips in 81 children with Perthes' disease and various forms of synovitis of the hip. The pressure was elevated in Perthes' disease (3.4 kPa), transient synovitis (17.3 kPa), septic arthritis (20.2 kPa), reactive arthritis (28.0 kPa) and arthritis with urticaria (32.3 kPa). In transient synovitis the mean pressure was only 2.3 kPa in flexion, while a mean of 26.6 kPa was seen in the neutral position and in internal rotation. In children with synovial effusion of the hip, the position of immobilisation should therefore be in flexion of 30-45 degrees with slight external rotation. The neutral position or extension, even with simultaneous traction, may endanger the circulation of the femoral head. PMID- 4036569 TI - Vitality of the slipped capital femoral epiphysis. Preoperative evaluation by tetracycline labeling. AB - In 25 cases with 29 slipped capital femoral epiphyses, treated with bilateral pinning, tetracycline was administrated preoperatively. Biopsies from the femoral head and the trochanteric region were analyzed by fluorescence microscopy. All had normal tetracycline labeling except the only patient with an acute severe slip. PMID- 4036570 TI - Incidence of hip fracture in Finland. A forecast for 1990. AB - From 1970 to 1980, cervical hip fractures in Finland increased by 55 per cent and trochanteric fractures by 46 per cent. The demographic pattern and increasing fracture risks in the elderly will cause twice as many hip fractures in 1990 as in 1970. PMID- 4036571 TI - Hip fracture in stroke patients. Epidemiology and rehabilitation. AB - With the purpose of identifying specific features in aged hemiplegic patients, 818 cases referred to a geriatric-rehabilitation hospital after hip fracture were studied. In 66 cases a cerebro-vascular accident had preceded the fracture, which was ipsilateral in 52 cases. No differences were found in incidence of concurrent disease, hospitalization time, mortality and functional recovery between hip fracture patients with and without a history of stroke, except that an interval of less than a week between stroke and fracture was associated with poor functional recovery. We conclude that rehabilitation of the stroke patient with hip fracture is worthwhile. PMID- 4036572 TI - Fracture healing in paraplegic rats. AB - In paraplegic rats, histomorphometric and chemical methods were used to evaluate callus production in tibial fractures stabilized by intramedullary nails. There were no differences in the mean sizes of fracture callus between paraplegic rats and their non-weight-bearing and weight-bearing controls. However, the variance of callus size was large in paraplegic rats. The concentration of nitrogen was high in calluses of paraplegic rats during the cartilaginous stage of healing. The hydroxyproline concentration did not differ between the groups. The rate of callus ossification was more rapid in paraplegic rats than in controls, but fracture calluses of paraplegic rats showed delayed accumulation of calcium and incomplete maturation of woven new bone. The results suggest that there are both mechanical and non-mechanical factors affecting callus formation in fractures below a spinal lesion. PMID- 4036573 TI - Effect of nerve injury on fracture healing. Callus formation studied in the rat. AB - In an attempt to determine the effects of peripheral nerve lesions on fracture healing, radiographic, histomorphometric and chemical methods were used to evaluate callus formation in tibial fractures of rats with sciatic denervation. Fracture union by bridging external callus was more rapid in denervated limbs than in controls. By contrast, external calluses of denervated fractures were smaller and less dense and contained less collagenous matrix (hydroxyproline) and minerals (calcium, phosphorus) than controls. The RNA/DNA ratio decreased more rapidly in denervated calluses than in controls. Mineralization of collagenous matrix (estimated from the calcium/hydroxyproline ratio) was not affected by denervation. PMID- 4036574 TI - Microsurgery in brachial plexus lesions. AB - Twenty-two patients with brachial plexus lesions were reviewed 3-6 years after microsurgical repair. Four patients underwent nerve transfer between intercostal nerves and the musculocutaneous nerve. None of these achieved useful elbow flexion. Nerve grafting mainly in the upper part of the plexus was performed in six patients of whom five recovered a useful motor function in at least one important area. Twelve patients underwent neurolysis; useful motor function in at least one important area was achieved in eight. We conclude that microsurgical treatment of brachial plexus lesions is useful in lesions of the upper part of the plexus, distal to the dorsal root ganglion. PMID- 4036575 TI - Shoulder function after deltoid muscle removal. AB - Postoperative function and muscular strength of the shoulder joint were studied in five patients who had undergone extirpation of the deltoid muscle because of a soft tissue tumor. No patient had significant functional impairment but all had a slightly limited range of active abduction and flexion. The strength reduction did not exceed 40 per cent in any position. PMID- 4036576 TI - Trapezium replacement arthroplasty. AB - Thirty-one patients (34 joints) with pain due to carpometacarpal joint derangement were reviewed 1/2 to 12 years after a trapezium replacement arthroplasty using a Swanson silicone prosthesis. At review, 25 hands were free from pain, and nine had some pain on exertion. Mobility and strength were generally well restored. The radiographic examination revealed 12 prosthesis fractures, three dislocations, and five cases of incongruity. However, all patients were satisfied with the results of the operation. PMID- 4036577 TI - Classification of distal radius fractures. AB - We analysed retrospectively a series of 269 distal radius fractures in adults in order to determine which of five different classification systems gave the best information about the radiographical prognosis of a fracture. The result after reduction in 195 cases was influenced mainly by the primary shortening, whereas dorsal angulation, radial displacement, and the age and sex of the patient were of minor importance. The system described by Older et al. in 1965, was superior to the others. In the analysis of the radiographical result after fracture union, the quality of the reduction, the Older classification system, and the age of the patient were the most important prognostic factors. We conclude that reduction of a distal radius fracture should primarily aim at correcting the shortening. PMID- 4036578 TI - The etiology of spondylolysis. A retrospective radiographic study. AB - One hundred and thirty-five patients with lysis in the fifth (lowest) lumbar vertebra and 24 patients with L4 lysis were compared retrospectively with respect to radiographic variables and the occurrence of trauma before symptom onset. Hypoplasia occurred only in the L5 lysis group, whereas trauma as a symptom precipitating factor was frequent in the L4 group. These observations suggest the possibility of different etiologies: trauma may contribute to lysis in a normal L4 vertebra, and inherited hypoplasia of the lumbosacral junction may lead to L5 lysis. PMID- 4036579 TI - Contribution of the cortex to epiphyseal strength. The upper tibia studied in cadavers. AB - Non-destructive measurements of compressive stiffness were carried out on 20 proximal tibial autopsy specimens. The tibial epiphyses were first loaded through a template covering all but the peripheral 2 mm of the subchondral resection surface, then through the whole resection surface, and finally, after removal of the peripheral shell. A slight increase of the stiffness coefficient resulted from peripheral contact. Stiffness increased significantly after removal of the shell, but several potential sources of systematic error in this part of the investigation raise questions as to the validity of this finding. The area corrected stiffness showed a decrease as a result of peripheral contact; this result indicates that the peripheral rim of bone has a lower area-corrected stiffness than the central bone, a finding which is incompatible with the concept of a true cortical shell at the epiphyseal level. PMID- 4036581 TI - Gentamicin-PMMA beads in the treatment of chronic osteomyelitis. AB - Fifty cases of chronic osteomyelitis, associated with septic arthritis in five cases, were treated with radical surgery, systemic antibiotics, and insertion of gentamicin-PMMA beads. Seven cases were lost to follow-up. The remaining 43 cases were followed up for an average of 14 months. All but four cases healed. PMID- 4036580 TI - Lack of effects of human calcitonin in osteogenesis imperfecta. AB - The effects of human calcitonin on bone mineral content and certain biochemical markers of bone metabolism were evaluated in a 2-12 month treatment period in seven patients with osteogenesis imperfecta. S-calcium, S-alkaline phosphatase, S immuno-reactive parathyroid hormone and the urinary excretion of calcium were found to be within the normal range before and during the treatment period. After 4-5 months of therapy, a slight increase in the urinary excretion of hydroxyproline was observed, but the values were still within the normal range. The bone mineral content, measured in the forearm, remained unchanged during the treatment period. Side effects were common, in two cases resulting in discontinuation of the treatment. We concluded that, with the dose of human calcitonin used, it was impossible to detect any beneficial effect in patients with osteogenesis imperfecta. PMID- 4036582 TI - Lumbar hernia in an iliac bone graft defect. A case report. AB - A hernia developed in the region of the inferior lumbar triangle of Petit 1.5 years after a full thickness bone graft had been taken from the part of the iliac crest that forms the base of the triangle. PMID- 4036583 TI - Femoral head necrosis following traumatic hip joint tamponade. A case report. AB - Necrosis of the left femoral head developed after a bicycle accident with undislocated acetabular fracture. 11/2 years later a Moore hemiarthroplasty was performed. The cause of the condition was probably hip joint tamponade. PMID- 4036584 TI - International Conference. The middle ear. Postoperative evaluation: anatomy, pathology, surgery and audiology. Antwerp, June 14-16, 1984. Part I. PMID- 4036585 TI - International conference. The middle ear. Postoperative evaluation: anatomy, pathology, surgery and audiology. Antwerp, June 14-16, 1984. Part II. PMID- 4036586 TI - [Hypopharyngeal carcinoma: analysis of oncological and functional results after surgery]. PMID- 4036587 TI - [Treatment of carcinomatous cervical lymph node metastases with the primary site unknown]. PMID- 4036588 TI - [Mass screening and early diagnosis of cancer of the upper aero-digestive tract]. PMID- 4036589 TI - [Correlations between bone conduction and speech audiometry in various functional states]. PMID- 4036590 TI - [Evaluation of stapedial reflex parameters in normal subjects]. PMID- 4036591 TI - [Evaluation of respiratory and cardiocirculatory function during adenotonsillectomy in relation to 3 different anesthesiological methods]. PMID- 4036593 TI - [Assessment of nasal patency by measurement of forced inspiratory flow]. PMID- 4036594 TI - [Clinical records of malignant tumors of the larynx]. PMID- 4036592 TI - [Evaluation of the immune response in patients with laryngeal cancer using specific and nonspecific tests: initial results of a follow-up in 80 cases]. PMID- 4036595 TI - Myofibroblasts in fibromatoses. An electron microscopic study. AB - Fifteen cases of fibromatoses were analyzed by electron microscopy, the objective being to compare the incidence and frequency of myofibroblasts in each category. Myofibroblasts were identified in all 15 cases and a considerably large number of these cells appeared in palmar fibromatosis, plantar fibromatosis, and nodular fasciitis. In keloid and cicatricial fibromatosis, however, only a small number of these cells were evident. In seven cases of extra-abdominal desmoid fibromatosis, the frequency of myofibroblasts in the component cells ranged from 10% to 64%, with a mean of 30%. The frequency was high in hypercellular lesions and low in hypocellular lesions, assuming that it would be roughly in parallel to the cellularity of the lesion in extra-abdominal desmoid fibromatosis and in other fibromatoses as well. There appeared to be no particular correlation between the number of myofibroblasts and recurrence of the lesion. PMID- 4036596 TI - Glomerular deposition of IgA in experimental hepatic cirrhosis. AB - Wistar rats rendered cirrhotic with carbon tetrachloride excreted significant proteinuria and hematuria. Serum levels of IgA and IgG were significantly elevated in cirrhotic animals. They showed mild mesangial proliferation and immunofluorescent studies revealed deposits of IgA and IgG predominantly in mesangial areas and along capillary walls. These findings were very similar to those seen in patients with hepatic cirrhosis or IgA nephropathy. The deposits of IgA were also found in hepatic tissue from cirrhotic animals. The intensity and distribution of glomerular IgA deposits were not diminished after treatment with acid buffer. These results suggest that glomerular IgA are IgA polymers and decreased hepatic clearance of hepatic IgA polymers may be responsible for the glomerular deposition of IgA. PMID- 4036598 TI - Nitrosamide-induced sarcomas in the gastric pylorus of hamsters. A histological and ultrastructural survey on the histogenesis. AB - A histological and ultrastructural survey on the histogenesis of N-methyl-N' nitro-N-nitrosoguanidine (MNNG)-induced gastric sarcomas in hamsters was attempted. Within 3 months after the beginning of oral administration of MNNG, simple spindle cell proliferation in the submucosal zone of the pyloric region of the glandular stomach was evident. By 5-6 months, the cells had acquired a sarcomatous appearance. Ultrastructurally, the spindle cells in the early stage, were divided into 3 types, i.e., angiogenic cells, fibroblastic cells, and primitive mesenchymal cells. Similarly, those in the late-appearing sarcomatous tumors were also classified into different types of angiogenic, fibroblastic, histiocytic and miscellaneous cells. Among the cell population of the 2 major groups, angiogenic cells were the most predominant cell type. Some morphological transition appeared to occur between the corresponding cell types at the early and late stages. DNA content of cell nuclei of the representative forms of the nitrosamide-induced sarcomas was higher than that of early appearing spindle cells. Thus, the evidence suggests that the early appearing spindle cells are precursors for the gastric sarcomas. PMID- 4036597 TI - pH-related differentiation in the epithelia of the gastric mucosa of postnatal rats. AB - The postnatal development of the gastric mucosa was observed in Long Evans rats. In both pyloric and fundic mucosae, the mitotic index peaked at 5 days of age and then gradually decreased to reach a constant level from 14 days of age onward (P less than 0.05), the germinal region shifted from the deeper area of the mucosae upward to the middle layer. The number of parietal cells increased gradually (P less than 0.05). Gastric pH on the mucosal surface decreased from 6 on the day of birth to about 4 at 7 days of age and to about 2 at 28 days of age. The inverse relationship between the number of parietal cells and pH value on gastric mucosa was found to be highly significant (P less than 0.01). Trehalase and sucrase activities were observed at 7 days of age and lactase and maltase activities from 0 to 14 days of age. In the pyloric mucosae, foveolae containing goblet cells which were positive for Alcian blue-PAS and HID were observed between 0 and 7 days of age. These cells disappeared by 14 days of age concurrently with the decrease in pH value and increase in the number of parietal cells. PMID- 4036599 TI - Intranuclear membranous profiles in germinoma cells--a variant of nuclear pockets and intranuclear annulate lamellae. AB - When ultrastructurally examining 24 germinomas comprising 12 seminomas, 4 dysgerminomas, 1 mediastinal germinoma, and 7 intracranial germinomas, intranuclear membranous profiles were noticed in 17 germinomas, ranging from 20 100 nm in width and 3 microns in length. With occasional connections to the nuclear envelope through a small hole, intranuclear membranous profiles in germinoma cells were considered as clefts of the nuclear envelope. While most frequently situated under the inner nuclear membrane, they varied in configuration as well as distribution. As sequestered round mass of nuclear material, they were a variant of nuclear pockets containing nucleoplasm. Intranuclear annulate lamellae were occasionally present apart from the nuclear envelope and connected with nuclear clefts. Eleven of the twelve seminomas and 6 of the twelve non-seminomatous germinomas showed intranuclear membranous profiles, and the incidence of such profiles was much higher in seminomas than in non-seminomatous germinomas. Intranuclear membranous profiles facing the inner nuclear membrane were also noted in spermatogonia in adolescents and adults. It was suggested that intranuclear membranous profiles in germinoma cells could be structures following ones occasionally seen in spermatogonia. PMID- 4036600 TI - Ultrastructural study of neuromuscular junctions in experimental autoimmune myasthenia gravis (EAMG) in rabbits. AB - Experimental autoimmune myasthenia gravis (EAMG) was produced in rabbits by the injection of acetylcholine receptor (AChR) protein from electric organ of Narkacion tokyonis with complete Freund's adjuvant, and the ultrastructural alterations of the neuromuscular junctions were studied. A lesion comparable to human myasthenia gravis could be observed in these animals. In acute EAMG, which showed a rapidly progressive severe paralysis 19 to 24 days after the first inoculation, distinct degeneration of the postsynaptic membrane was observed. Sometimes an irregular gap was found between the nerve terminal and postsynaptic sarcoplasm. In chronic EAMG with mild and prolonged muscle weakness, which appeared 23 to 54 days after the first inoculation, poorly developed junctional folds with little degenerative change were seen. By a morphometric analysis, some of the changes were detected even in a subclinical EAMG. In the presynaptic region, there was no ultrastructural alteration except that an increase of nerve terminal area was observed in chronic and subclinical EAMG. The pathogenesis of these alterations was discussed. PMID- 4036601 TI - Intravascular bronchioloalveolar tumor. Report of an autopsy case and review of literature. AB - An autopsy case with intravascular bronchioloalveolar tumor occurring in a 51 year-old Japanese woman is reported. The lungs contained multiple nodules which were characteristic features of this tumor. In addition, the tumor diffusely involved bilateral lower lobes associated with extensive pleural invasion. And the tumor tended to spread along vascular and bronchial trees. No extrathoracic metastasis was noted. Histologically, the nodules showed hypocellular hyaline or myxoid tissue surrounded by peripheral cellular layers. Diffuse consolidated areas were composed of collagenous connective tissue with scattered tumor cells. Factor VIII-related antigen could not be demonstrated in tumor cells, but the negative result was considered to be secondary to antigen deterioration by delayed fixation of the tissue. Electron microscopic examination did not support the alveolar epithelial cell origin, but revealed morphological characteristics of myofibroblasts and endothelial cells. The tumor is presumed to be derived from vascular stem cell with a tendency of endothelial differentiation. PMID- 4036602 TI - Chromium-induced pulmonary cancer. Report of a case and a review of the literature. AB - A 57-year-old man, whose occupational history was that of a chromate worker for about 35 years, suffered nasal perforation during and died due to pulmonary cancer. In the autopsy materials, the concentration of chromium in the lung tissues was very high, being about 90 times the amount found in normal lungs. The chromium particles in the lung tissues could not be detected by analytical electron microscope, but they could be found in the anthoracotic lesions of the lungs by means of an X-ray microanalyser. The present case was judged to be a case of chromium-induced pulmonary cancer since all the pathologic data obtained were similar to those found in similar cases reported in the literature. PMID- 4036603 TI - The nature of "blue nevus" in cystic teratomas of the ovary. An ultrastructural evidence for Schwann cell origin. AB - The ultrastructural findings of two cases of "blue nevus" in ovarian benign cystic teratomas are described. The bipolar or dendritic pigmented cells showed features of Schwann cells with melanin synthesis, but not of ordinary melanocytes. This study supports the neural origin of blue nevus. PMID- 4036604 TI - Vibrio vulnificus septicemia. AB - A 33-year-old Japanese male, who had a three year history of biopsy-proved liver cirrhosis, was admitted to the hospital on June, 24, 1983 with a sudden onset of fever (38.6 degrees C), chills, generalized pain, nausea, anorexia, weakness, and eruption over the entire body. The patient went into shock and died about 7 hours after admission. Blood cultures before death were positive for V. vulnificus. Postmortem microscopic examination revealed "necrotizing vasculitis" in the small and large intestines, stomach, and skin, and also showed marked toxic epidermal necrolysis. This case matches the primary septicemia caused by V. vulnificus described by Blake et al. In addition, this case suggests that the septicemia was acquired through the gastrointestinal tract, especially the small intestine, because the V. vulnificus was isolated from blood and numerous Gram-negative bacilli around the submucosal vessels were observed in the area with acute necrotizing vasculitis. PMID- 4036605 TI - Fibromuscular dysplasia of middle cerebral and renal arteries. Report of a case with autopsy verification. AB - A patient with fibromuscular dysplasia of both the left middle cerebral artery and the right renal artery is described. The patient, a 38-year-old Caucasian female, died of subarachnoid hemorrhage following rupture of a saccular aneurysm of the left middle cerebral artery one month after surgical intervention for renovascular hypertension. PMID- 4036606 TI - Internal carotid and vertebral arteries of spontaneously hypertensive and normotensive rats. A morphometric study on extracranial, intraosseous and intracranial arterial segments. AB - Arteries from spontaneously hypertensive rats (SHR) and Wistar Kyoto controls (WKY) were investigated. Specified cross-sections were collected from the extra- and intracranial parts of the internal carotid arteries, from the carotid segment situated in the skull bone and from intra- and extracranial segments of the vertebral arteries. The internal radius, media thickness and ratio between media thickness and internal radius (m/r ratio) were calculated for a standardized condition implying a smooth and circular internal elastic membrane. The m/r ratio was significantly increased in all arterial segments of 7-month-old SHR compared to WKY. This was caused mainly by decrease of radius in the vertebral arteries and in the intracranial carotid segment. In the extracranial and intraosseous carotid segments the increase of m/r ratio in SHR was mainly due to an increase of media. Whereas the radius was the same in the intra-osseous and intracranial carotid segments of WKY, the m/r ratio was greater intracranially. The results suggest that the physical properties of supporting tissues may influence the normal arterial development and modify the influence of an increased arterial pressure on the vessel wall. PMID- 4036607 TI - Simultaneous occurrence of a granulosa cell tumour and a serous papillary cystadenocarcinoma in the same ovary. A case report. AB - This report describes a previously unreported collision of a papillary serous cystadenocarcinoma and a granulosa cell tumour with a sarcomatoid growth pattern in the same ovary of a seventy-five year old woman with no endocrinological abnormality. The patient died from widespread dissemination of the adenocarcinoma. PMID- 4036608 TI - Chondromyxoid fibroma. A review of the literature and a report on our own experience. AB - The present paper comprises a review of the literature on chondromyxoid fibroma (CMF) and a report on nine cases originally classified as CMF, found in a review of all curetted bone lesions at our department from 1955 to 1978. At histologic revaluation only two cases fulfilled the criteria for true CMF, whereas six were classified as other benign bone lesions and one proved to be a chondrosarcoma. The chondrosarcoma case after recurrence was subjected to more mutilating surgery than would have been necessary if correct diagnosis had been established initially. The other six benign cases were all well and without signs of recurrence 5-11 years after curettage. In one of the two true CMF cases, i.e. in a young boy, there were for 2 years postoperatively radiological signs of a progressive recurrence, which was left without treatment, since the patient was well. Interestingly, radiograms 2 and 11 years postoperatively essentially showed the same picture, indicating spontaneous cessation of the process. Chondromyxoid fibroma is an extremely rare lesion. Histologic misinterpretation is not uncommon. In sporadic cases this may have serious implications. It may be questioned whether surgical treatment of CMF in young patients, known to have a high recurrence rate, is mandatory. PMID- 4036609 TI - Histochemistry of sacrococcygeal chordoma. AB - A characteristic feature of chordomas is the content of a great amount of mucinous material. A sacrococcygeal chordoma surgically removed from a 76-year old man was histochemically investigated in order to obtain some information about the composition of the mucopolysaccharides. From the results of the staining reactions, we concluded that they are of the acid category and probably a mixture of weakly sulphated and carboxylated glycoproteins. PMID- 4036610 TI - Effect of aerobic and anaerobic atmosphere on the detection of micro-organisms from blood cultures. AB - Blood from patients with suspected bacteraemia was simultaneously cultured in two Vacutainer blood culture bottles containing 45 ml of supplemented peptone broth (Becton Dickinson), five ml of blood in each bottle. The cultures were incubated at 37 degrees C for seven days. One of the bottles was vented and the other unvented. A total of 3958 blood culture sets were processed during the 20-month period of the study. Altogether 438 (11%) of the blood culture sets were positive. Of the 438 isolates, 317 (72%) were detected in both bottles, 61 (14%) in the vented bottle and 60 (14%) in the unvented bottle. A total of 60 (14%) isolates would not have been detected if only five ml of blood had been cultured. Only minor differences in the isolation rates of different bacterial and fungal species from the vented and unvented bottles were found. The results indicate that aerobic incubation of Vacutainer bottles with supplemented peptone broth is sufficient in routine diagnostic work. PMID- 4036611 TI - Effect of human leukocyte and other tissue dialysates on Listeria resistance and phagocytosis in mice. AB - The effect of dialyzable transfer factor (TFd) on Listeria resistance was measured by survival studies and by assessing phagocytic capacity of peritoneal macrophages. Unfractionated dialysates from human leukocytes (DLE), bovine liver, porcine spleen and kidney as well as saline were injected i.p. into NMRI mice 72 h before the i.p. injection of 1-3 x 10(6) Listeria organisms. The results show that DLE, porcine spleen and bovine liver dialysate increased the LD50 5-20 times. Porcine kidney dialysate had no effect on the survival of the mice. After the fractionation of porcine spleen dialysate on Sephadex G-10 column, a significant activity was found in two fractions, II and IX. When active fractions were given together (II + IX) i.p. three days prior to the infection with listeria organisms, the survival of mice increased significantly, whereas no effect was seen when the fractions were given i.v. and the bacteria i.p. Also the treatment with active fractions increased significantly the phagocytic capacity of peritoneal macrophages. Taken together, our results suggest that the Listeria protective substances seem to operate via monocyte activation. PMID- 4036612 TI - Cytotoxic factor(s) released from stimulated mouse peritoneal macrophages. AB - Mechanisms of macrophage-mediated cytotoxicity against a tumor-cell line (L-929 cells) were analyzed. Culture supernatants were harvested from mouse peritoneal macrophages cultivated for 3 days in the absence or presence of the stimulating agents Escherichia coli endotoxin or zymosan. The supernatants from stimulated cultures were cytotoxic for the tumor cells, evaluated by measuring release of radio-activity during subsequent 4 days' culture of 14C-thymidine-labelled tumor cells in the supernatants. Cytotoxicity was verified by counting cells per culture. Corresponding results were obtained from co cultures of stimulated macrophages and tumor cells, in accordance with a previous study. Selective release of af lysosomal enzyme (beta-glucuronidase) was shown in the supernatants from endotoxin- or zymosan-stimulated cultures, while reduced levels of glucose were seen in all supernatants from macrophage cultures. Dialysis of supernatants against fresh medium reduced the toxic activity somewhat. Dialysis restored the glucose content to optimal levels, while the enzyme activity was unchanged. Heating of supernatants to 56 degrees C for 30 min reduced the cytotoxicity along with a reduction in enzyme activity; 70 degrees C for 30 min removed both cytotoxic activity completely. Heating had no effect on the glucose content of the supernatants. The present data indicate that macrophage-mediated tumor cytotoxicity may be performed through release of heat-labile soluble factor(s) which co-variate with the secretion of a lysosomal enzyme from stimulated macrophages. PMID- 4036613 TI - Neutrophil recruitment in skin window chambers--activation by complement. AB - Complement was studied in skin window chambers, a human model of neutrophil recruitment in acute aseptic inflammation. Autologous plasma activated by the alternative pathway served as attractant; control chambers were filled with a balanced salt solution or with non-activated plasma samples. Neutrophil accumulation during a 24-hour period was consistently enhanced by activated complement in all of 15 healthy volunteers. Control chambers showed negligible cell counts. Reference assays revealed 1) consumption of the centrally placed complement component, C3, 2) generation of chemotactic activity as assessed in Boyden chambers by the standard complement activation procedure. Simultaneously obtained responses to activated complement in skin window chambers and in the Boyden assay of chemotaxis showed a highly significant, positive correlation. Our results demonstrate that the biological capacity of complement includes stimulation of neutrophil migration during simulated in vivo conditions and thus extends previous observations in animals. PMID- 4036614 TI - [Chemotherapeutic studies on schistosomiasis. XXXVI. Synthesis of derivatives of 4-phenyl-and 4-allyl-5-(pyrazinyl-2)-1, 2, 4-triazole-3-thio-ketone]. PMID- 4036615 TI - [Studies on the Chemical constituents of Menispermum dauricum DC]. PMID- 4036616 TI - [Application of orthogonal function spectrophotometry to the determination of the coenzyme Q10 content in the injection]. PMID- 4036617 TI - [Morphological and histological studies of the Chinese drug bai-jiang-cao: I. Drugs derived from Valerianaceae]. PMID- 4036618 TI - [Studies on antineoplastic action of indirubin derivatives and analogs and their structure-activity relationships]. PMID- 4036619 TI - [Synthesis of 16-(m-chlorophenoxy)-17, 18, 19, 20-tetranor-prostaglandin F2 alpha]. PMID- 4036620 TI - [Steroidal sapogenins from mildewed Dioscorea collettii Hook. f]. PMID- 4036621 TI - [The application of computer to volumetric analysis of drugs: the assay of weakly acidic water-soluble drugs]. PMID- 4036622 TI - [Studies on PVC membrane anisodamine selective electrodes]. PMID- 4036623 TI - [The antifertility action of anordrin and its effect on plasma levels of progesterone in rabbits]. PMID- 4036624 TI - [A comparative study on the photodynamic inactivation of tumor cells in the presence of several hematoporphyrin derivatives]. PMID- 4036625 TI - [A new type of peripheral vasodilator, the compound CH-141 in solution. III. Decomposition kinetics of CH-141]. PMID- 4036626 TI - [Preclinical and clinical pharmacokinetic study of orally administered effervescent acetylsalicylic acid tablets]. PMID- 4036627 TI - [Correlation between protonization coefficients measured in aqueous and water ethanol solutions]. PMID- 4036628 TI - [Reaction kinetics of the dissolution of acetylsalicylic acid and salicylic acid in aqueous solution. I. pH and temperature dependence of salicylic acid decomposition]. PMID- 4036629 TI - A simple reversed phase TLC method for stability-indicating assay of digoxin. PMID- 4036630 TI - Impaired maternal behaviour and altered central serotonergic activity in the adult offspring of chronically ethanol treated dams. AB - Female rats were given 16% ethanol solution as the sole liquid during the entire period of gestation. At birth the offspring was removed and reared by foster dams consuming normal tap water. At adult age the female offspring showed deficiencies in their maternal behaviour; they built nests of poor quality and they displayed prolonged times for retrieving pups placed outside the nest. In the whole brains of the prenatally ethanol-exposed females a decreased serotonin synthesis was observed. The offspring of the prenatally ethanol exposed mothers did not show any signs of disturbances in physical or behavioural development. PMID- 4036631 TI - Task-dependent development of cross-tolerance to psychomotor effects of lorazepam in man. AB - Development of cross-tolerance between lorazepam and four other benzodiazepines (BZ) was studied in two trials by measuring objective psychomotor performance and by subjective assessments. In trial I, nitrazepam 10 mg (NZ), temazepam 20 mg (TZ) or placebo were administered to 14 healthy students for 10 consecutive nights. After each pretreatment, psychomotor impairment by the challenge dose of lorazepam 3 mg (LZ) was measured. In trial II, responses to LZ after pretreatment with diazepam 5 mg (DZ) (8 subjects) or alprazolam 0.25 mg (AZ) (10 subjects), both t.i.d., were compared to LZ responses measured after one-month wash-out period. In trial I no cross-tolerance between BZs was found in objective tests, and LZ induced exophoria was even increased. However, the subjects rated LZ to cause less drowsiness after pretreatment with NZ in a situation where the manifestation of cross-tolerance was facilitated by ingestion of caffeine. In trial II a clear but task-dependent development of tolerance to the challenge dose of LZ was documented. One-week pretreatment with DZ reduced subjects responses to LZ. The total serum BZ activity bioassayed by radioreceptor method after intake of LZ was significantly (P less than 0.05) higher after pretreatment with DZ than in the end of wash-out period. Thus a functional cross-tolerance was documented on complex tasks after the subjects have been continuously working under DZ burden. PMID- 4036632 TI - Role of glutathione and hepatic glutathione S-transferase in the biliary excretion of methyl mercury, cadmium and zinc: a study with enzyme inducers and glutathione depletors. AB - The effect of hepatic glutathione (GSH) depletion and enzyme induction on hepatic glutathione S-transferase (GST) activity, biliary excretion of GSH, methyl mercury, cadmium and zinc was studied in rats. The GSH depletors, methyl iodide and diethyl maleate, did not influence hepatic GST activity but, depending on the substrate used, benzo(a)pyrene, phenobarbital, pregnenolone-16 alpha-carbonitrile (PCN) and trans-stilbene oxide (TSO) increased it by 16-33, 44-89, 53-97 and 208 279%, respectively. GSH depletors decreased (-88%), benzo(a)pyrene and TSO did not affect, phenobarbital and PCN increased (+113 and +149%) the transport of GSH into bile. The biliary excretion of methyl mercury, cadmium and zinc was reduced by GSH depletors (-97, -74 and -93%), and enhanced by phenobarbital (+139, +280 and +220%) and PCN (+150, +121 and +160%). Treatment with benzo(a)pyrene and TSO did not affect the excretion of methyl mercury and zinc into bile, but decreased that of cadmium. These results do not provide evidence for the role of hepatic GST but strongly support the importance of biliary GSH excretion in the hepatobiliary transport of methyl mercury, cadmium and zinc. It is assumed that phenobarbital and PCN enhance the biliary excretion of these metals by increasing the transport of GSH, the carrier molecule, from liver to bile. PMID- 4036633 TI - Local tissue damage after intramuscular injections in rabbits and pigs: quantitation by determination of creatine kinase activity at injection sites. AB - The creatine kinase (CK) method, which is based on difference in CK activity at injection sites and in control tissue, was used for quantitation of local tissue damage after intramuscular injection of varying volumes and preparations in rabbits and pigs. Injections were given in the central part of the longissimus dorsi muscle. Three days after the injections the animals were killed and the arbitrary amounts of tissue without CK were calculated from the CK activity in muscle tissue at the injection sites and in control tissue. Determination of tissue damage by the CK method was in good agreement with macroscopic and microscopic changes, whether a well demarcated necrotic area or little or no necrosis was found at the injection site. Tissue damage was proportional to injection volumes between 0.25 and 1 ml in rabbits and 0.5 and 3 ml in pigs. In rabbits tissue damage per injected ml was found to be more than twice the damage seen in pigs. It is concluded that the CK method is a reliable method for quantitation of local tissue damage after intramuscular injections and that injection of even small volumes of 0.25-0.5 ml in the longissimus dorsi muscle of rabbits is a sensitive test of the local toxicity of drugs. PMID- 4036634 TI - Effects of amiflamine and related compounds on the accumulation of biogenic monoamines in rat brain slices in vitro and ex vivo in relation to their behavioural effects. AB - The inhibition of the accumulation of serotonin, noradrenaline and dopamine in rat brain (occipital cortex and striatum) slices by amiflamine and its two major metabolites FLA 788(+) and FLA 668(+) was examined and compared with that of amine releasing compounds e.g. p-chloroamphetamine (PCA) and alpha ethyltryptamine and uptake inhibitors, e.g. alaproclate, citalopram, desipramine, fluoxetine and norzimeldine. It was found that amiflamine and FLA 788(+) inhibited the accumulation of serotonin and noradrenaline but only slightly that of dopamine in vitro and ex vivo with a mechanism similar to that of PCA and alpha-ethyltryptamine, i.e. with higher potency in reserpinized rats than in normal animals suggesting amine releasing mechanisms. Similar to alpha ethyltryptamine and PCA, amiflamine and FLA 788(+) caused behavioural changes (serotonin syndrome) which were particularly pronounced in reserpinized rats but also observed after a second administration of amiflamine in normal rats. Upon repeated administration of amiflamine the behavioural changes disappeared which indicates a functional down-regulation of the serotonin receptors responsible for this syndrome. FLA 668(+) inhibited the accumulation of noradrenaline in vitro and ex vivo but had less effect on the accumulation of dopamine and particularly that of serotonin. It is concluded that amiflamine and FLA 788(+) inhibit the accumulation of serotonin and noradrenaline by releasing mechanisms and that the released serotonin triggers the behavioural changes observed. PMID- 4036636 TI - Abstracts of the XVI Annual Nordic Meeting on Biological Alcohol Research. Stockholm, Sweden, May 12-15, 1985. PMID- 4036637 TI - Studies on absorption and distribution of ginsenoside Rg-1 by whole-body autoradiography and chromatography. PMID- 4036635 TI - Calcium uptake in rat brain synaptosomes after short-term exposure to organic solvents: a pilot study. PMID- 4036638 TI - Biotransformation of terodiline. II. Disposition in the male rat. Identification of metabolites in rat urine and rat liver microsomes by mass spectrometry. PMID- 4036639 TI - Influence of drug concentration and ageing on the release of salicylic acid from a Carbopol hydrogel. PMID- 4036640 TI - Studies on tabletting properties of lactose, Part I. The effect of initial particle size on binding properties and dehydration characteristics of lactose. PMID- 4036641 TI - Effects of physical training and detraining on resting cardiovascular parameters in albino rats. AB - The time course of shifts induced by physical training in the resting cardiovascular parameters was investigated in swim-trained albino rats. Measurements were performed weekly, both during a 14-weeks training period and 5 weeks after cessation of regular swimming. Cardiac output (dye dilution) blood pressure (electromanometry) and heart rate (ECG) were measured under intraperitoneal urethan anesthesia. In comparison with non-exercising controls, rats at the end of the training period displayed lower heart rate, smaller stroke volume and cardiac output, and a higher peripheral resistance. The early phase of regular training, however, was characterized by an elevated cardiac output, heart rate and stroke volume, and by a decreased peripheral resistance. After discontinuation of regular training, cardiac output was elevated as well, but this was brought about only by the increased stroke volume, because resting heart rate was still lower than in the controls. Blood pressure did not change during the whole experimental period. Considering that similar shifts have been reported in humans, the changes in the resting cardiovascular status may be responsible for the similar complaints and symptoms often observed in undertrained athletes or in athletes who had interrupted high intensity regular training. PMID- 4036642 TI - Establishment of modern examining procedures for diagnosis of porphyrias. AB - Reversed-phase high-performance liquid chromatography together with fluorescence detection is suitable for the determination of urinary porphyrin carboxylic acid isomers, and Copro I and III, as well as Uro I and III porphyrin isomers are separated simultaneously. PMID- 4036643 TI - Time course of denervation diuresis and natriuresis in the anaesthetized rat. AB - The effect of unilateral renal sympathectomy on renal excretion of water and sodium was studied in three groups of Inactin-anaesthetized rats: 1-3, 4-19, and 20-35 weeks after denervation. Increased sodium excretion from the denervated kidney in the absence of changes in GFR was observed up to 35 weeks following renal denervation. Thus, in a functional sense, renal reinnervation may have only been partial during the time interval studied. PMID- 4036644 TI - Recording of sinus node electrogram: its technique, electrophysiological and clinical importance. AB - The electric sign of sinus node activity, the sinus node electrogram, was recorded in animal experiments and in 22 patients. In humans the electric sign of the sinus node precedes the atrial activation by 60 msec on the average. Atrial impulse conduction time is somewhat longer than the sinoauricular one. Canine sinus node electrogram is very similar to that recorded in humans but sinoauricular impulse conduction is somewhat quicker in dogs. The pathological importance of the sinus node electrogram is discussed. PMID- 4036645 TI - Changes in the transaminase activities in the middle and posterior silk-gland tissues of eri-silkworm, Philosamia ricini, in relation to spinning process. AB - The middle silk gland tissue of eri-silkworm exhibits a higher glutamate oxaloacetate transaminase activity (about twice) than that of the glutamate pyruvate transaminase, while the posterior silk gland tissue exhibits a higher (three to four times) glutamate-pyruvate transaminase activity than that of the glutamate-oxaloacetate transaminase. PMID- 4036646 TI - Quantity of DNA in the organs of 19-day-old foetuses after AET, MEA, or 5-HT treatment of mice on the first day of gestation. AB - On the first day of gestation, Porton mice were injected intraperitoneally with AET (2-aminoethylisothiouronium bromide hydrobromide), MEA (cysteamine hydrochloride,) or 5-HT (serotonin-creatinine sulphate), in a dose of 40 mg/kg of bodyweight. On the nineteenth day of pregnancy, the fresh weight of both heart and kidneys of foetuses, as well as DNA content in 25 mg of fresh tissue and in these whole organs were analysed. DNA was extracted from the foetal organs by means of Burton's method, which is based on the estimation of deoxiribose content in the colour reaction with diphenylamine. As compared to controls, in the remaining groups of mice lower fresh weight of both heart and kidneys of foetuses, greater DNA content in 25 mg of fresh tissue and smaller total amounts of DNA in the whole organs were found. Among the experimental groups of mice, statistically significant differences in the analysed values were observed between the group of animals treated with 5-HT and the remaining groups, with the exception of statistically non-significant difference in the DNA content of the whole kidneys between those injected with 5-HT and MEA. PMID- 4036647 TI - Composition of amino acid phosphates in phosphorylated G-actin of rabbit skeletal muscle. AB - In our experiments the phosphorylation of actin was studied. Similar investigations have been published in the literature, however very long incubation time was applied in these studies and even so a low incorporation of phosphate concentration was found. The present phosphorylation experiments were performed using short incubation periods as usual in our myosin investigations and was characterized by an unexpectedly high phosphate saturation. We suggest that in suitable incubation medium the nucleotide- and phosphate-free actin prepared by using phosphate- and ATP-free solutions takes only 1 minute to become saturated, while in its peptide chain a N-P bond type acid labile phosphate is formed. On maximum saturation 9 M P-arginine, 0.4 M P-histidine and some minor phosphorylated derivatives can be observed. After a longer period of incubation, with a lower incorporation of phosphate (3 mol P) a more stable phosphorylated actin is formed. As a result of preparation and gel filtration a dimer and a monomer form of actin can be obtained. Both of them exhibit the basic properties of actin (polymerization, myosin-ATPase activation) and the phosphate incorporation described in this paper. PMID- 4036648 TI - Membrane symposium. Sumeg, May 15-18, 1984, Hungary. Abstracts. PMID- 4036649 TI - On some presynaptic effects of an aminotetraline derivative. AB - The article studies the effect of a newly-synthesized aminotetraline derivative with code 1b on some presynaptic mechanisms of nerve transmission. Compound 1b (1 X 10(-9) M) increases the contractions of electrically stimulated isolated rat anococcygeal muscle: on the background of cocaine (1 X 10(-7) M), the contractile response after 1b is potentiated, whereas after phentolamine (1 X 10(-9) M) compound 1b does not increase the contraction of the muscle. Compound 1b in concentration from 1 X 10(-8) M to 1 X 10(-7) M manifests a concentration dependent potentiating effect (EC50-3.95 X 10(-8) M) on the contractile response of electrically stimulated isolated rat vas deferens. The alpha-adrenergic blocker yohimbin (1 X 10(-7) M) and compound 1b (1 X 10(-6) M) increase the contractions of electrically stimulated mouse vas deferens. The potentiating effect of 1b is eliminated by clonodone (1 X 10(-19) M) and haloperidol (1 X 10( 5) M). On electrically stimulated guinea-pig ileum 1b (2 X 10(-6) M) and morphine (1 X 10(-6) M) inhibit the contractions of the isolated organ, while their combined administration potentiates the inhibitory effect of morphine. Both the combined and the independent effects of 1b and morphine are eliminated by naloxone (1 X 10(-6) M) and 4-aminopyridine (1 X 10(-7) M). Both compound 1b (2 X 10(-6) M) and morphine (1 X 10(-6) M) manifest potentiated inhibitory effect on the contractile response of guinea-pig ileum, administered on the background of dopamine (1 X 10(-5) M) and haloperidol (1 X 10(-6) M).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4036650 TI - Ontogenetic development of the monoamine oxidase activity and of the metabolism of biogenic monoamines in rat brain. AB - The article examines the ontogenetic development of the monoamine oxidase activity and of the metabolism of the dopamine, noradrenaline and serotonin in the brain of newborn, 10-day-, 20-day- and 2-month-old rats. Monoamine oxidase activity is determined using three substrates: tyramine, serotonin and beta phenylethylamine. Monoamine oxidase A (substrate serotonin) and the total monoamine oxidase activity (substrate tyramine) are found to manifest identical development, their activity increasing quickly after birth, to reach constant values after the 10th day. The general course of the development during the first ten postnatal days shows that the post partum increase in the total monoamine oxidase activity in rat brain is predominantly due to monoamine oxidase A. Monoamine oxidase B (substrate beta-phenylethylamine) develops after the 10th postnatal day. Evidently monoamine oxidase A plays a decisive role for controlling the level of the biogenic monoamines in the young organism during the first days of the ontogenesis. Investigation of the changes in the content of dopamine, noradrenaline and serotonin in the age groups of the experimental animals chosen reveals a rapid increase in the dopamine and noradrenaline levels even during the first ten days of the ontogenesis. The increased total monoamine oxidase activity and the increased dopamine content correspond to its increased turnover rate during ontogenesis. The turnover rate of noradrenaline remains unchanged between the 10th and 20th postnatal days. The increasing serotonin level between the 20th and 60th post partum days corresponds to its increased turnover rate. PMID- 4036651 TI - Interaction of the input atrial excitatory waves and conduction through the atrioventricular node. I. Changes in the cellular electrical activity. AB - Extrasystoles were applied only at the posterior input, only at the anterior input and jointly at both AVN-inputs in preparations from rabbit right atrium, after 10 basic beats. The effect of the interaction of the input excitatory waves was evaluated by the changes in the cellular electrical activity and in the output H1H2-interval. It has been demonstrated that both the summation effects (shortening of the H1H2-interval) and the inhibition effects (prolongation of the H1H2-interval) are accompanied by substantial changes in the spatial-temporal organization of conduction within the node. The summation of excitatory waves leads to higher velocity of AP increase (most frequently in the N-zone), to changes in the shape of AP as a result of electrotonic influences, to changes in the sequence of activation of cellular group forming different conduction pathways. The inhibition of the excitatory waves is related to the increase in the inhomogeneity of conduction, manifested in the formation of competitive conduction pathways. In addition to the changes in the AP-front, a typical characteristic is the hill-structure reflecting the effect of the excitatory fronts. The formation of conduction pathways under the effect of each of the input excitatory waves probably takes place on the background (spatial and temporal) of the disappearing refractoriness, related to another excitatory wave. The interaction between the input excitatory waves, taking places through the proposed model, could also be present in a normally functioning heart provided the phasic correlations between the moments of activation of the posterior and anterior inputs are optimal for such an interaction. PMID- 4036652 TI - Changes in the uterine epithelial cell size of white Leghorn hens under tropical summer stress. PMID- 4036653 TI - Coping with cancer: psychological dimensions. AB - Cancer has a profound psychological impact upon the patient and his family, and the psychological responses, primarily of the patient himself, the close family, physician and nursing personnel, but also of the extended family, and society in general, become a complex interrelationship. Some of the most important psychological aspects of cancer are reviewed. These include the psychological responses of the patient, such as denial, vulnerability, coping strategies, hope, depression, suicide, reaction to diagnosis, and the management of the family, and the psychological responses and attitudes of the physician and nursing personnel. Based on the above psychological analysis some guidelines are offered to help in coping with cancer. PMID- 4036654 TI - Contribution of adverse drug reaction to admission rates in an acute psychiatric ward. AB - The relative contribution of adverse drug reactions (ADR) to the admission rate of an acute psychiatric ward was examined prospectively. Among 321 patients hospitalized over a period of 17 months, adverse drug reactions were the main cause for hospitalization in 7.5%. Extrapyramidal side effects - mainly resistant akathisia - account for half of these patients. The population at high risk was that of the elderly and those suffering from organic brain syndromes. PMID- 4036655 TI - DST in healthy volunteers and after sleep deprivation. AB - The dexamethasone suppression test (DST) was performed in 46 healthy volunteers and repeated in nine of them following total sleep deprivation (TSD). While only 2 postdexamethasone cortisol values were insufficiently suppressed (greater than 5 micrograms %) in control DSTs, 5 postdexamethasone cortisol values were above 5 micrograms % following TSD. The mean postdexamethasone value was increased from 1.55 +/- 1.06 to 4.47 +/- 5.86 micrograms % following TSD at 8.00 h. The authors conclude that sleep deprivation as a therapeutic approach and prolonged sleeplessness may bias DST results. PMID- 4036656 TI - Home assessment and treatment in a community psychiatric service. AB - The work of a new community-based crisis intervention team is described. 326 psychiatric emergencies were seen over a period of 3 years. An increasing proportion of these were acutely psychotic at the time of assessment. Home treatment was effective for a significant number of patients, including those with a previous history of hospital admission. Some practical and theoretical aspects of the service are discussed. PMID- 4036657 TI - Reliability and validity of two tests for non-verbal memory. AB - Because of its lenient effects on memory, unilateral electroconvulsive therapy (ECT) on the non-dominant hemisphere is routinely used in most ECT units in the Scandinavian countries. Considering the neuropsychological peculiarities of the non-dominant hemisphere, two tests were constructed to evaluate the effect of ECT on non-verbal memory. The tests are characterized by visual mode of administration and complex figurative items. They can measure both immediate and delayed memory and exist in two parallel forms. Analysis of a number of studies on unilateral non-dominant and dominant ECT indicates that the two non-verbal memory tests have good reliability and validity. Convergent validity between the two non-verbal memory tests, discriminant validity against tests of verbal memory, and criterion-related validity in relation to the influence of different treatment modalities, indicate the tests as valid instruments for measuring non verbal memory. The two test forms show satisfactory parallelism. Together with tests of verbal memory, the total battery provides an all-round instrument for studying memory functions after ECT or other cerebral influences. PMID- 4036658 TI - Content of grandiose phenomenology across cultures. AB - The content of grandiose ideas and delusions in patients of various cultural groups admitted to a London psychiatric hospital were compared. There were no overall differences but certain trends were apparent. It was found that religion was the commonest content of grandiose symptoms in all the groups. Its frequency was higher in the African and Jamaican groups, an observation that can be understood from the cultural background of these groups. The other types of content, namely royals, identity and ability were less frequent in all groups. PMID- 4036659 TI - Platelet MAO activity as a biological marker in subgroups of alcoholism. AB - In the Stockholm Adoption Study, two types of alcoholism, "Type I" and "Type II", have been identified on the basis of genetic predisposition. In the present study, this classification has been applied to a clinical sample. The two types of alcoholism were clinically clearly identifiable. Type I alcoholism was characterized by late onset and few social complications. Type II alcoholism was characterized by early onset, use and abuse not only of alcohol, but also of glue, cannabis, amphetamine and opioids, together with several social complications. The subjects with Type II alcoholism had also more alcoholism and depression among their first-degree relatives than the subjects with Type I alcoholism. Furthermore, the two types of alcoholism were separable by means of the biological marker - platelet MAO activity. While platelet MAO activity was normal in Type I alcoholics, as compared with healthy controls, it was clearly low in the Type II alcoholics. This subclassification of alcoholism seems to be of value in future studies concerning the etiology, epidemiology and treatment of alcoholism. PMID- 4036660 TI - Cross-cultural study of religious phenomenology in psychiatric in-patients. AB - Case notes of patients from nine different cultural groups admitted to a London hospital were scrutinized for religious background and religious phenomenology. With the exception of preaching behaviour there were no statistically significant cultural differences, but certain trends were apparent. The pattern of religion in each cultural group could be understood in terms of the historical and geographical origins of these groups. Religious phenomenology was better explained in terms of deep-seated cultural factors rather than current religion. PMID- 4036661 TI - Post-partum mental illness in northern Nigeria. AB - All the major psychotic disorders observed following childbirth in the West also occur among patients in Northern Nigeria. The age at onset of post-partum mental disorder is observed to be lower among Northern than Southern Nigerian women; this, in the authors opinion, is probably because women in Northern Nigeria are generally "given out" to their spouses in early teenage. The study also comments on a probable entity of "pure puerperal psychosis." PMID- 4036662 TI - Development of a screening method for probable somatizing syndromes. AB - "Somatizing syndromes" is proposed to describe all conditions in which patients present with somatic complaints but without signs of organic disease. Fifty consecutive G.P. patients were given a Swedish version of the 52-item Illness Behaviour Questionnaire (IBQ) to test whether this questionnaire identifies those with signs of somatizing syndromes. The patients were also independently categorized by the G.P. into seven clinical groups reflecting the presence or absence of somatic disease, social/psychological problems and various combinations thereof. The test-retest reliability of the IBQ expressed as Pearson's r was 0.89. Patients presenting with concern over non-existing somatic disease and apparently unaware of any related psychological problem had significantly higher mean IBQ scores than did other patients. The IBQ was thus found to be a satisfactory instrument for primary identification of patients with probable somatizing syndromes. PMID- 4036663 TI - The development of an integrated psychiatric service in a Scottish community. AB - The deployment of a specialist psychiatric team and closer integration with primary health care practitioners has led to a greater proportion of first contacts as out-patients being seen compared with national data, and a relatively lower in-patient admission rate. The increase was in those patients seen in health centres rather than in additional out-patient clinics. Despite this there is evidence of a slow accumulation of patients with psychosis whose main requirements is suitable supported accommodation. Such a deployment into the community is a more economic use of resource and can, with advantage, assist the traditional hospital-based services in the transition from a custodial role. PMID- 4036664 TI - Memory for events occurring under anesthesia. PMID- 4036665 TI - Introduction of a new metric for the analysis of ear advantage in a dichotic single-response test. PMID- 4036666 TI - [Fragmentation characteristics of the polyether antibiotic complex isolated from Streptomyces hygroscopicus strains IM-110-81 and IM-111-81 (DIKLS) in mass spectrometry]. PMID- 4036667 TI - [Taxonomic studies of Streptomyces hygroscopicus strain IM-110-81 (DIKLS)- producer of a polyether antibiotic complex]. PMID- 4036668 TI - [Isolation, purification and separation of the antibiotics produced by Streptomyces hygroscopicus IM-110-81 (DIKLS)]. PMID- 4036669 TI - [Use of bacterial enzyme preparations in the production of Bulgarian cheeses. IV. Comparative studies of white brined cheese at different seasons of the year]. PMID- 4036670 TI - [Effect of ochratoxin A and other intracellular metabolites on the phosphogluconate metabolic pathway in Aspergillus ochraceus]. PMID- 4036671 TI - Extinction, reinstatement and spontaneous recovery of conditioned suppression in rats and the stability of conditioned inhibitor performance. AB - Acquisition of the suppressive properties of a conditioned stimulus (CS), terminating with shock, and of the attenuating properties of the conditioned inhibitor (CI), signaling that shock will not be given at the end of the CS, proceed at similar rates. The attenuation of suppression exerted by the CI and the decrement of the suppression due to extinction differed in both the time course and the distribution of barpresses within the CS duration. After extinction the CS still retained some suppressing properties, which were limited to the last 20-30 s, whereas the CI attenuated the suppression throughout the duration of the CS. Extinction of the suppressive properties of the CS did not change the attenuating properties of the CI. The recovery of the suppressive properties of the CS after presentations of unsignaled reinstating shocks or after a long pause in experimental sessions was incomplete and shortlasting. Both procedures did not change the properties of the CS presented in compound with the CI. PMID- 4036672 TI - Relationship between the release and uptake of noradrenaline by rat brain synaptosomes in the formation of defensive conditioned reflex. AB - The defensive conditioned reflex with two-way avoidance was developed in rats in a shuttle-box. Immediately and 30 min after learning the animals were decapitated and synaptosomes were isolated from the whole brain and brain cortex. Using [14C] and [3H]-noradrenaline (NA), the processes of uptake, spontaneous and potassium depolarization-induced (60 mM KCl) release of NA by brain synaptosomes of trained and control animals were studied in vitro. Immediately after learning the inhibition of NA uptake was observed, but 30 min following learning the ability of synaptosomes to take up NA was recovered to the initial level. Thirty minutes after learning the potassium depolarization-induced release of NA previously taken up by synaptosomes increased as compared to the control. NA spontaneous release did not change under these conditions. With the increase of Ca2+ concentration in the incubation medium from 1.2 mM to 2.4 mM, the induced NA release from brain synaptosomes of trained and control animals regularly increased. Changes in NA release and uptake are specific for the development of conditioned reflex PMID- 4036673 TI - The functional organization of the descending influences in the non-projection corticothalamic systems of the cat brain. AB - The local cooling of parietal, frontal or motor cortical areas; in cats under Nembutal anesthesia changed evoked potentials (EPs) in pulvinar, lateral posterior and medial dorsal thalamic nuclei. Parietal cortex, cooling led to rapid and significant changes of visual EP and delayed but strong changes of somatic EP in the pulvinar-lateral posterior complex. In contrast, frontal cortex cooling led to fast changes of somatic EP in medial dorsal nucleus and caused delayed weak changes: of visual EP. Motor cortex cooling resulted in rapid transformations of both potentials, though the changes of somatic EP were more pronounced in medial dorsal nucleus. The modifications of both EP primary-and secondary components were modal- and system-dependent. Results suggest that polysensory cortical areas exert modal-specific corticofugal influences on signals of different modality or on signals of the same modality but different subcortical genesis in the association nuclei. PMID- 4036674 TI - Changes in intracranial pressure and epidural pulse waveform following cold injury. AB - Using anaesthetized spontaneously breathing cats, intracranial pressure (ICP) was monitored for twenty hours following the insult of cold injury; simultaneous recordings were also made of cerebral blood flow (CBF), epidural pulse waveform (EDP-WF), and systemic arterial pressure (SAP). Results could be divided into two groups depending on whether or not ICP exceeded 30 mmHg. In group one, in which marked increase in ICP including occasional episodes of pressure waves were observed, an initial increase in CBF and the changes in EDP-WF from polyphasic to monotonous at about 20 mmHg were characteristic. On the other hand, in group two, ICP never exceeded 30 mmHg, CBF slightly and continuously decreased and EDP-WF was polyphasic throughout the course. There were no significant differences in trends in SAP, in the extent of spread of oedema and in water content of the white matter between both groups. Therefore, the amount of cerebral blood volume (CBV) due to cerebral vasodilatation was considered to account for the further increase in ICP. Moreover, changes in EDP-WF were regarded as a useful indicator in predicting the trends in ICP since these changes could be observed in a relatively lower pressure range prior to a marked increase in ICP. PMID- 4036675 TI - Long-term effects of partial callosal lesions. Preliminary report. AB - Ten patients with partial callosal lesions were investigated with a broad scale neuropsychological assessment. Nine patients with a variety of lesions affecting midline structures have been operated using a direct transcallosal approach, one patient with a callosal lipoma remained unoperated. Sophisticated studies of the interhemispheric transfer of somaesthetic and perceptual motor tasks, as well as psychometric testing related to parameters of memory and attention performance were applied. The results indicate that there is no clear correlation between the site of callosal lesion and clinical symptoms. Although special disconnecting symptoms due to callosal dissection could be found, they didn't reach clinical significance. The most severe symptoms of impairment were caused by the extracallosal pathology. The results indicate that the transcallosal approach is a safe and feasible alternative in the management of pathological lesions in the midline region. PMID- 4036676 TI - Intraoperative ultrasonography through a burr-hole. AB - Intraoperative ultrasound diagnosis through a burr-hole was performed in 22 cases using a 5 MHz electronic sector-scanning transducer. The pathology along with the landmarks, such as ventricles and the interhemispheric fissure, were visualized. In two cases, a second burr-hole was placed nearby, and aspiration of the fluid was accomplished under real-time ultrasonic monitoring using the first hole as an acoustic window. Our results suggest a possibility of ultrasound-guided stereotactic surgery of the brain through twin burr-holes. PMID- 4036677 TI - Cerebrospinal fluid and plasma vasopressin during short-time induced intracranial hypertension. AB - The response of plasma and ventricular cerebrospinal fluid vasopressin concentration to short-time induced intracranial hypertension was studied in 8 patients with hydrocephalus, defined as ventricular enlargement on computerized tomography. In connection with measurement of conductance to cerebrospinal fluid outflow, the concentration of vasopressin in plasma and cerebrospinal fluid was measured during perfusion at a low (less than 10 mmHg) and at a high (greater than 20 mmHg) intraventricular pressure level. Mean plasma vasopressin concentration was increased from 2.4 +/- 0.4 pg/ml (SEM) during perfusion at the low pressure level to 4.2 +/- 0.8 pg/ml (p less than 0.01) at the high pressure level. The cerebrospinal fluid concentrations of vasopressin at the low and high intraventricular pressure were 1.2 +/- 0.1 pg/ml and 1.7 +/- 0.2 pg/ml (p less than 0.05), respectively. However, only half of the patients responded to the increase in intraventricular pressure with an increase in cerebrospinal fluid vasopressin concentration exceeding 50%. The results of the present study suggest that an increase in the intracranial pressure might be a stimulus for vasopressin release in both the blood and the cerebrospinal fluid. PMID- 4036679 TI - Universal plate for anterior cervical spine osteosynthesis. Technical note. PMID- 4036678 TI - Increased concentration of hypoxanthine in human central cerebrospinal fluid after subarachnoid haemorrhage. AB - The adenine nucleotide metabolites hypoxanthine, xanthine and uric acid were determined by high performance liquid chromatography in cerebrospinal fluid (CSF) from 25 patients with subarachnoid haemorrhage (SAH) and from 26 control subjects. In addition, the haemoglobin and protein levels in the CSF of the patients were determined. In 13 subjects, from which lumbar CSF was collected three, six and nine days after SAH, there was a gradual increase in 8 patients for hypoxanthine and in 3 of the 13 patients for xanthine and uric acid. The mean concentrations were not significantly higher than the controls. In 12 SAH patients, consecutive CSF fractions of 10 ml were collected peroperatively during surgical clipping of aneurysms. The hypoxanthine concentrations increased continuously from lumbar to central CSF samples. Hypoxanthine levels were 6.5 +/- 1.0 microM in lumbar CSF compared to 11.8 +/- 2.3 microM in central CSF (p less than 0.001), while xanthine, uric acid, haemoglobin and protein levels were equally distributed. Furthermore, the SAH patients showed about 3 times higher concentrations of central CSF hypoxanthine (p less than 0.01) and xanthine (p less than 0.05) while that for uric acid was similar compared to all control subjects. Also, as in vitro study showed that the increased concentrations of the adenine nucleotide metabolites could not be caused by degradation of blood components in the subarachnoid space. It is presumed that the increased central CSF concentrations of hypoxanthine that were demonstrated in patients after SAH could be a sensitive marker for brain tissue ischaemia. However, since there was no correlation between the hypoxanthine levels, clinical condition or cerebral vascular diameter, other factors have to be excluded before ischaemia alone could explain the elevated central hypoxanthine levels in patients without major clinical dysfunction after SAH. PMID- 4036680 TI - Effects of needle shape on the integrity of the vascular endothelium. AB - Lesions generated by the passage of micro-needles through vessel walls are of concern because any lesion may significantly alter hemodynamics of an anastomosis. To study this problem, three different needles were tested on the exposed carotid arteries of 30 rats: the 100 mu taper point, the 100 mu cutting point, and the 75 mu taper point. Trauma generated by the penetration of needles was tested first as the needle and its attached suture was passed through the vessel, then the suture was left in place. One hour after penetration, the arteries were prepared for scanning electron microscopy. Differences between the 100 mu taper point and the 75 mu taper point were significant in terms of size and extent of lesions. An arc of endothelial cells surrounding the wounds showed flattening, tissue destruction and clotting. To minimize endothelial trauma, taper point needles are superior to cutting needles. The 100 mu cutting needle caused damage to the vessel wall in tissue cutting on needle penetration, causing a slit-like incision, and in aggregation of platelets at the puncture site. PMID- 4036681 TI - Polyacryl prosthesis for cranioplasty--their production in silicon rubber casts. AB - The frequently observed osteolysis after reimplantation of deep-frozen skullcap bone have led us to use polyacryl as the material of choice if a secondary covering of a skull bone defect becomes necessary. Polyacryl has an excellent biological compatibility but often yields unsatisfactory cosmetic results when the modelling is done at the site of the intervention, especially in the case of defects in the forehead region. A method is described that allows the preparation of a prosthesis before the actual operation identical with the original bone in every detail. The surgery is then confined to the anchoring of the prosthesis to the bone edges. PMID- 4036682 TI - Scanning electron microscopic findings on the rabbit meninges after local lavage with Polyvinylpyrrolidon-Jod-Komplex. AB - The microbicide Polyvinylpyrrolidon-Jod-Komplex (P.J.K.) was experimentally evaluated for its use in local lavage of the epidural space. In 20 rabbits a lumbar laminectomy was performed followed either by local lavage with P.J.K. or with NaCl. After one month the meningeal covering of the operated spinal cords revealed no signs of fibrosis or arachnoid adhesions when studied macroscopically or by scanning electron microscopy (SEM). PMID- 4036684 TI - [The apical meatus in the surgery of hypospadias]. PMID- 4036683 TI - Normal pressure hydrocephalus: correlation between CT and measurements of cerebrospinal fluid dynamics. AB - Twenty-nine patients consecutively admitted for consideration of CSF diversion surgery for suspected communicating ("normal pressure") hydrocephalus underwent cranial computerized tomography (CT) and study of cerebrospinal fluid (CSF) absorption, the latter determined as resistance to outflow of CSF (Ro). From the CT the size of the ventricular system was determined by various linear measurements and ratios and the presence of periventricular lucencies (PVL) and the size of cortical sulci was noted. Except for absence of cortical sulci greater than 3 mm no CT feature was suggestive of compromised CSF absorption. On the other hand, cortical atrophy did not rule out increased resistance to CSF outflow. Features thought of as characteristic for normal pressure hydrocephalus on CT: large ventricles as compared with the amount of cortical atrophy and presence of PVL, correlated poorly with measured high resistance values. There was no correlation between the size of the ventricular system and resistance to CSF outflow. In the diagnostic distinction between communicating ("normal pressure") hydrocephalus and cerebral atrophy (hydrocephalus ex vacuo) static CT cannot replace an actual determination of CSF outflow resistance. PMID- 4036685 TI - [Primary hyperthyroidism and lithiasis]. PMID- 4036686 TI - [Absence of precipitating effect of uric acid on calcium oxalate]. PMID- 4036687 TI - [Cutaneous uretero-ileostomy in bladder carcinoma]. PMID- 4036688 TI - [Hormonal treatment of disseminated cancer of the prostate: results and survival obtained in a series of 60 patients]. PMID- 4036689 TI - [Post-adenectomy urinary incontinence]. PMID- 4036690 TI - [Cyst of Skene's gland communicating with the urethra]. PMID- 4036691 TI - [Pyoderma gangrenosum of the penis]. PMID- 4036692 TI - [Leiomyoma of the prepuce. Presentation of a case]. PMID- 4036693 TI - [Effects of vasectomy on the rat testicle: ultrastructure study]. PMID- 4036694 TI - [Intraperitoneal bladder perforation by a permanent bladder catheter]. PMID- 4036695 TI - Biomechanics of the primate skull base. PMID- 4036696 TI - Drugs affecting lipid metabolism VIII. Proceedings of the Eighth International Symposium on Drugs Affecting Lipid Metabolism, July 27-30, 1983, Philadelphia, Pennsylvania. PMID- 4036697 TI - Proapolipoprotein A-I metabolism in the human and the rat. PMID- 4036698 TI - Apoprotein measurements. PMID- 4036699 TI - Apolipoprotein E mutants, hyperlipidemia and arteriosclerosis. PMID- 4036700 TI - Mechanisms of action of absorbable hypolipidemic drugs. PMID- 4036701 TI - Effects of nicotinic acid and its derivatives on lipid metabolism and other metabolic factors related to atherosclerosis. AB - Nicotinic acid treatment thus induces several beneficial effects on serum lipoproteins and on hemodynamic factors related to the risk for development of atherosclerosis. It effectively reduces the atherogenic lipoproteins VLDL and LDL and also increases the anti-atherogenic HDL, mainly the HDL2 fraction. The drug seems to be active not only in decreasing the synthesis of various lipoproteins but also to enhance the removal into peripheral tissues, thereby speeding up the catabolic events of serum lipoproteins. The mode of action of NAc in adipose and muscle tissue needs further evaluation to better understand the complex interplay between free fatty acid and glucose and insulin metabolism. The recent findings of a stimulation of prostacyclin formation as well as a reduction in platelet aggregation are newly discovered favorable effects of the drug that needs to be further examined. Although the drug seems to induce some undesirable side effects (reversible), its several favorable anti-atherosclerotic properties should stimulate both experimental and clinical research with this drug. Hopefully newer derivatives with even better tolerance may be developed. PMID- 4036702 TI - HMG-CoA reductase inhibitors. PMID- 4036703 TI - Fate of cholesteryl linoleyl ether injected into rats as chylomicrons, acetylated LDL and HDL. PMID- 4036704 TI - Hypertriglyceridemia: lipoprotein receptors and atherosclerosis. AB - We have shown first, that apoB mediates the binding of small VLDL Sf 20-60 and IDL, as well as LDL, to the LDL receptor. Second, apoE of an appropriate, accessible conformation is required for the binding of large VLDL to the LDL receptor; HTG-VLDL Sf greater than 60 but not normal VLDL Sf greater than 60 have this apoE population. Third, the same population of apoE that mediates binding of HTG-VLDL Sf greater than 60 to the LDL receptor modulates its binding to the beta VLDL receptor, but it is not required for the latter interaction. Fourth, a domain of processed apoB or apoB-48 in association with a domain of the inaccessible apoE is required for binding to and uptake by the beta-VLDL receptor. Fifth, our observations suggest that the abnormal catabolism of VLDL that occurs in hypertriglyceridemia may be explained by the abnormal uptake of HTG-VLDL by either the LDL or the beta-VLDL receptor pathway. Finally, we suggest that plasma proteases may route apoB/E-containing lipoproteins to macrophages for disposal, and this results in foam cell formation. PMID- 4036705 TI - Hypertriglyceridemia and atherosclerosis analysis of an abnormal lipoprotein system and potential beneficial effects of triglyceride lowering therapy. PMID- 4036706 TI - The role of hydrophobicity in the structure of the human plasma lipoproteins. PMID- 4036707 TI - Metabolism of apolipoproteins and the metabolic heterogeneity of apo B in the rat. PMID- 4036708 TI - Both NK sensitive and resistant mycoplasma free cell lines stimulate release of NKCF. PMID- 4036709 TI - Aberrant oxygen metabolism in neoplastic cells injured by cytotoxic macrophages. PMID- 4036710 TI - AIDS-associated syndromes. Proceedings of the International Conference on AIDS Associated Syndromes. December 8-9, 1984, Irvine, California. PMID- 4036711 TI - Comparison of type I and type II diabetes. Similarities and dissimilarities in etiology, pathogenesis, and complications. PMID- 4036712 TI - Immunological aspects of type 1 and 2 diabetes mellitus. AB - IDDM occurs predominantly among individuals being class II antigen HLA-DR 3 and/or 4 positive, while NIDDM is not associated with HLA-D. Although the HLA-DR 3 or 4 specificities are prerequisites for IDDM to develop, their high frequencies (about 60%) in the background population preclude tissue typing as a predictive test, underlined by the observation that less than 50% of monozygotic twins are concordant for IDDM. The presence of a number of immune abnormalities argues that the causes of IDDM may be sought in an altered immune reaction against antigens present in the pancreatic B cells and/or in the environment. The majority of IDDM patients of short duration show both cellular and humoral autoimmunity against the pancreatic B cells. Similar phenomena may be observed in patients initially diagnosed as NIDDM and treated with oral hypoglycemic agents. It has been speculated that these patients have a retarded form of IDDM. It is possible that the combination of specific Class II antigen molecule(s) and an invading antigen (virus, bacterium, chemical etc.) presented to the immune system triggers the formation of effector cells such as B lymphocytes and cytotoxic T lymphocytes which also cross-react with the pancreatic B cells. Multiple exposures to this or related antigens throughout several years may eventually lead a sufficient loss of pancreatic B cells to cause insulin dependence. PMID- 4036713 TI - Basis of the present classification of diabetes. AB - The present classification of diabetes most widely used is that recommended by the National Diabetes Data Group and subsequently endorsed by the World Health Organization. This classification is primarily a clinical classification of diabetes because in most instances the etiology is unknown. The need for a standardized classification arose out of the recognition that diabetes was a syndrome rather than a single disease and the different terminologies which emerged. While certain types of diabetes can be classified according to specific etiology or associations with specific syndromes, the vast majority cannot. Insulin-dependent and noninsulin-dependent diabetes usually represent syndromes whose etiopathology is believed to differ and their clinical characteristics are usually distinctive. As evidence of etiological heterogeneity has increased there has been a tendency to adopt the terms Type I and Type II diabetes to indicate different etiologies, although the original usage of these terms was as a clinical classification to differentiate between insulin dependent and non insulin-dependent disease. At present the use of the four terms to describe the common types of diabetes leads to confusion, which could readily be resolved by arriving at agreed definitions for each of these terms. While the NDDG-WHO classification has served to standardize terminology and stimulate research into the different causes of diabetes, some further refinement of the classification, together with some additional definition of terms, should be considered. The classification of diabetes most widely used at the present time is that suggested by the National Diabetes Data Group (NDDG) in the United States in 1979, which was subsequently recommended by the World Health Organization (WHO) Expert Committee on Diabetes Mellitus in 1980. It should be stressed that this classification was intended to be a uniform framework for clinical and epidemiological research, and that the classification would almost certainly have to be modified on the basis of new knowledge in the future. PMID- 4036715 TI - Atherosclerosis, the major complication of diabetes. PMID- 4036714 TI - Insulin-mediated and non-insulin-mediated metabolic effects of gastroenteropancreatic peptides in type I and type II diabetes. AB - In this brief review of regulatory function of gastroenteropancreatic peptides in control of intermediary metabolism in normal and diabetic states, with and without mediation by insulin and/or glucagon, a variety of possible mechanisms have been described. It is apparent that the pharmacologic actions of the peptides identified in various locations provide models for multiple routes of delivery and modes of action of effectors in this control system. Examples already exist of each of the hypothetical mechanisms illustrated in the scheme in Figure 4. It is clear that a great deal of study will be necessary in identification of the active agents and assessment of their importance in the physiology of intermediary metabolism. With respect to the possible pathophysiologic roles of regulatory peptides of the gastroenteropancreatic system other than insulin and glucagon, a number of considerations of Type I and Type II diabetes have been raised. The balance of the evidence suggests that Type I diabetes may be viewed as an insulin deficiency syndrome, so that physiological replacement with insulin may be expected to result in correction of the metabolic abnormalities. Nevertheless, the difficulty of physiologic replacement treatment, which may call for portal delivery of insulin, is well recognized, and abnormalities secondary to insulin deficiency even in "well-treated" Type I diabetes may be compounded by the effects of gastroenteropancreatic peptides other than insulin, exerted through the various mechanisms discussed. In Type II diabetes mellitus, current understanding of the pathophysiology is much less complete and no convincing description of the etiology exists. The various metabolic actions of the gastroenteropancreatic peptides, and their interactions with other endocrine, paracrine and nervous regulatory mechanisms, represent a dauntingly complex control system. The elucidation of this system can provide fertile ground for the development and testing of hypotheses for the pathophysiology of disordered metabolism in Type II diabetes mellitus. PMID- 4036716 TI - A comparison of kidney disease in type I and type II diabetes. AB - Diabetes is the most important cause of ESRD in the Western world. Type I and II diabetes appear to contribute importantly to ESRD although, obviously, the prevalence of ESRD is higher in Type I. Microalbuminuria may predict later development of overt clinical nephropathy in both Type I and Type II patients. In both diabetes subtypes current evidence favours the dysmetabolism of diabetes as causative. There are clinical observations in Type I and renal morphologic evidence in Type II indicating that risk of nephropathy is, in part, related to the magnitude of hyperglycemia. Institution of strict glycemic control fails to reverse established clinical nephropathy in Type I diabetes. Efforts to determine if precise regulation of blood sugar can prevent nephropathy in patients with Type I and Type II diabetes are currently incomplete. PMID- 4036717 TI - Diabetic neuropathy. AB - The incidence and prevalence of diabetic neuropathies in Insulin Dependent (IDDM) and Non-Insulin Dependent (NIDDM) Diabetes Mellitus is not known because in previous studies the heterogeneity of diabetes and of the neuropathies was not taken into account, criteria for diagnosis and surveillance for neuropathy were variable, and studies were not prospective or population based. We have begun such prospective epidemiologic studies using a uniform algorithm for the classification of the diabetic disorders and uniform and validated approaches for the assessment of symptoms, neurologic deficits and various quantitative end points of neural dysfunction. As regards cause, a key question which we are trying to answer is whether hyperglycemia and associated metabolic alterations affect neural tissue directly or whether there is an intervening tissue alteration between metabolic derangement and tissue change. Improved control of hyperglycemia does not appear to be associated with rapid neurologic improvement, possibly arguing for an intervening tissue alteration. The recently observed decrease in nerve oxygen tension and blood flow in streptozotocin diabetes suggests that an alteration of the nerve microenvironment may relate importantly to the cause of diabetic neuropathy. PMID- 4036718 TI - Limitations and problems of diabetes classification from an epidemiological point of view. AB - There are residual ambiguities between the two main current glycaemic definitions of the categories of DM, IGT and normal GT which should be resolved. IGT is clearly a highly heterogeneous category and could with advantage be resolved into its identifiable subsets though adequate data for this is not yet available. The concept of insulin dependency requires clearer definition for operational purposes. Biochemical parameters (e.g. C-peptide responses) may help. Attempts to combine clinical manifestations and pathogenic mechanisms in a single classification (e.g. IDDM/NIDD versus Type I/Type II) should be handled with care. If the term Type I is to be retained, it should be applied to a defined pathogenic process, not to a clinical type of DM. The term Type II is inadequately defined at present. IDDM and NIDDM, clinical descriptive terms, may be provoked by a variety of pathogenic mechanisms (i.e. they are 'heterogeneous'). They could be subclassified by mechanism (when known). More visibility should be given in classification to non-Europid forms of DM (e.g. 'Tropical or 'Nutritional' DM). A staging dimension should be recognised in classifications of DM. Future classifications will benefit from the incorporation of the presence or absence of susceptibility/resistance factors to diabetes itself or to its severe long term sequelae. There remain uncertainties about the definitions and clinical implications of gestational DM (and gestational IGT) not discussed above. It should be accepted that different user groups may need different subclassification of diabetes and glucose intolerance to meet their specific requirements and so long as this is made clear and definitions are adequate this should not be a problem. However, for the present, all groups should accept the proposed glycaemic definitions of DM or IGT for the purposes of comparability. PMID- 4036719 TI - The Wisconsin Epidemiologic Study of Diabetic Retinopathy. A comparison of retinopathy in younger and older onset diabetic persons. AB - In a population-based survey of diabetic persons, retinopathy was detected by stereoscopic color fundus photography in 70% of persons under 30 years of age at diagnosis and taking insulin (Group YO), in 62% of persons 30 years of age or older at diagnosis and taking insulin (Group OO-I) and in 36% of persons 30 years of age or older at diagnosis not taking insulin (Group OO-N). The mean duration of known diabetes was 14.6 years in Group YO, 11.0 years in Group OO-I and 6.9 years in Group OO-N. After 20 years of diabetes, proliferative retinopathy was present in about 50% of Group YO, about 25% of Group OO-I and about 5% of Group OO-N. After 15 years of diabetes, macular edema was present in about 18% of Group YO, about 20% of Group OO-I and about 12% of Group OO-N. When present, macular edema tended to be associated with more hard exudate in Group OO-N. PMID- 4036720 TI - [The possibility of improving the adaptability of preschool children to school]. PMID- 4036721 TI - [Pedagogic-psychologic aspects of the diagnosis and development of school ability in East Germany]. PMID- 4036722 TI - [Responsibilities of the adolescent physician in the evaluation of specific requirements and final examination of students of the 9th and 11th grade]. PMID- 4036723 TI - [Manifestations and expression of motor activity in normally intelligent, concentration disordered, restless students in teaching]. PMID- 4036724 TI - [Priorities of school health in relation to historical conditions and viewpoints]. PMID- 4036725 TI - [Responsibilities of commissions for lowering infant and child mortality- retrospective and prospective aspects exemplified by the Karl-Marx-Stadt district]. PMID- 4036726 TI - Haemodynamic response to postural stress in the elderly with and without postural hypotension. AB - The haemodynamic response to postural stress (60 degrees foot-down tilt) was measured by impedance cardiography in six elderly cardiovascular-normal patients and 39 with symptomatic postural hypotension (systolic blood pressure drop greater than or equal to 20 mmHg or more). In the normal elderly the mean increase in heart rate, fall in blood pressure and cardiac output, and rise in peripheral resistance was less than that described in younger subjects. The changes were at their maximum in 1 min, and there was little further change over the next 5 min. In those with postural hypotension, orthostatic reduction (or failure to rise) of the peripheral resistance was the mechanism in 83% of cases, whatever the cause, and the time course of the haemodynamic changes was the same in the majority as in the normals. Serial tests in patients whose postural hypotension was controlled (by cessation of causal drugs, often multiple, by fludrocortisone, or by dihydroergotamine) showed return to normal. PMID- 4036727 TI - Living conditions and health of a population aged 85 years or over: a five-year follow-up study. AB - The population aged 85 years or over (n = 674) living in Tampere, Finland was surveyed in 1977-78. Altogether 561 persons (83%), 99 men and 462 women, were examined. A re-examination of 170 persons, 23 men and 147 women, was carried out in 1982 by the same procedure as in 1977-78, The results were compared with those of the same people and with those of over-90s five years before. Of the group followed, in the initial survey 65% were living at home and 25% in old people's homes, 10% being hospitalized. The percentage of hospital in-patients had increased threefold during the five-year follow-up. The functional capacity of the subjects had deteriorated as regards mental function and ability to walk. The mean values of blood samples (apart from ESR) were still in normal ranges, although the levels of haemoglobin and haematocrit had fallen significantly. Dementia or confusion, anaemia, femoral-neck fracture and cataract were significantly increased. PMID- 4036728 TI - The Guillain-Barre syndrome in the elderly: clinical and electrophysiological features of five cases. AB - The Guillain-Barre syndrome is an important cause of polyneuropathy in the elderly. The clinical and electrophysiological features of five cases are presented. Electrophysiological investigation has a valuable role in the diagnosis of this condition in the elderly. PMID- 4036729 TI - CIGMA assessment of insulin resistance and pancreatic beta cell function in the elderly. AB - Ten elderly subjects aged 71-85 years and with no indication of diabetes had an oral glucose tolerance test (OGTT) and a one hour's continuous infusion of glucose with model assessment (CIGMA) to assess the pathophysiology of glucose intolerance. All had fasting plasma glucose less than 6 mmol/l and glycosylated haemoglobin levels less than 8.8%, but seven had impaired glucose tolerance during the OGTT. The CIGMA similarly assessed glucose tolerance (rs = 0.65, P less than 0.02), and in addition showed increased insulin resistance and low normal beta cell function. PMID- 4036730 TI - Duodenal ulcer disease in the elderly: a retrospective study. AB - A retrospective study was performed of 163 patients aged 65 years and over with a diagnosis of duodenal ulceration admitted to one Health District over a period of six years. Eighty per cent of the patients were admitted with acute complications, 50% bled and 30% were perforated. A large proportion of these patients were currently taking anti-inflammatory agents. Patients managed surgically for their complications had a high mortality rate but this was even higher for those managed conservatively. Giant ulcers were found to occur frequently in this age group which had a tendency to severe bleeding. It is concluded that early diagnosis and prompt surgical intervention is essential in the management of complications associated with duodenal ulceration in the elderly. PMID- 4036731 TI - The effects of age on muscle strength and anthropometric indices within a group of elderly men and women. AB - Within a group of 184 subjects (100 females) aged 65-90 years living independently, age was found to have a significant negative correlation with strength of triceps surae in the calf and biceps brachii in the arm. Muscle area in the limbs also declined significantly with age in males. Weight and strength per cross-sectional area in the calves declined significantly with age in females. Superficial fat did not change with age; height declined, perhaps due to kyphosis. The strength of the calf compared to body weight also declined significantly with age in both sexes. Multiple regression analysis has been used to describe the effects of sex, age and weight on muscle variables. PMID- 4036732 TI - Is the Amerlex free-thyroxine assay a useful screening test in the elderly? AB - The results of screening 1140 acutely-ill elderly patients with the Amersham Amerlex FT4 assay are presented. Nonthyroidal illness was the commonest cause of abnormal results and we stress the importance of performing confirmatory tests in this group of patients. PMID- 4036733 TI - Heatwave morbidity and mortality in old age. AB - Mortality in the elderly is affected by external temperature at both extremes. Admissions to a geriatric unit during the hot summer of 1983 were compared with those in the same period in 1982, a typically British summer. There were 382 admissions and 69 deaths in 1982, and 468 admissions and 90 deaths during the same 22-week period in 1983. The principal difference in the cause of admissions was in the group cerebrovascular accidents/transient ischaemic attacks/subarachnoid haemorrhages which rose from 10% in 1982 to 15% in 1983. There was also a small increase in the proportion of respiratory-tract infections in 1983. PMID- 4036734 TI - [Experimental and clinical studies on calcium urolithiasis: (I) Animal model for calcium oxalate urolithiasis using ethylene glycol and 1-alpha (OH) D3]. AB - As calcium oxalate stones are the most important component in urolithiasis, an experimental model has to be designed to clarify the pathogenesis and aid in their prevention. Hyperoxaluria as well as hypercalciuria were produced in rats by administering ethylene glycol (0.5%, in drinking water administered ad libitum) and 1-alpha (OH) D3 (0.5 micrograms/rat given every other day), respectively, for three to four weeks. Neither drug alone produced stones efficiently as did the combination regimen of these two compounds. The occurrence of stones was 77.3%, and with only a moderate degree of renal functional impairment. Biochemical and histological data were obtained using this model. PMID- 4036735 TI - [The residual calculi in conservative operation for renal calculi]. AB - One hundred and three kidneys with calculi in 100 patients, were treated by conservative renal surgery from Jan., 1980 to Dec., 1982. The operative technique consisted of pyelolithotomy, extended pyelolithotomy, dismembered pyelolithotomy, nephrolithotomy (bivalve or anatrophic nephrolithotomy) partial nephrectomy and pyelo-nephrolithotomy. Intraoperative X-ray and coagulum lithotomy were employed when pyelolithotomy was performed. Thirty-five residual calculi in 20 kidneys were observed on postoperative X-ray film. The rate of residual calculi was 19.4%. Factors causing residual calculi, were analysed on these 103 kidneys. The factors were as follows; the shape of calculi: staghorn calculus with multiple small calculi, the shape of the renal collecting system: narrow pelvis with narrow caliceal neck and dilatated calices, and the operative technique: nephrolithotomy. These results suggested that it would be necessary to minimize residual calculi when performing nephrolithotomy. PMID- 4036736 TI - [Lymphadenectomy for renal cell carcinoma]. AB - The techniques, results and problems of lymphadenectomy were assessed in 56 cases of renal cell carcinoma. As the approach to the retroperitoneum, the thoracoabdominal approach was used in 22 cases and transabdominal approach in 34 cases. Radical nephrectomy was performed, followed by lymphadenectomy. All of the regional lymph nodes were dissected. The mean time required for lymphadenectomy was 1 hour and 40 minutes and the mean volume of blood loss was 350 ml. As intraoperative complications, vascular injury occurred in 3 cases. In 1 of these cases the left second lumbar vein was injured. Therefore, in lymphadenectomy caution should be exercised not to give injury to this blood vessel. The postoperative complication observed included bleeding and chylous ascites in 1 case each. In performing operations one must ligate the lymphatic vessel carefully. The 5-year-survival rate for 6 cases associated with metastasis to lymph node was 33%. From this fact, it was postulated that lymphadenectomy is helpful to improve prognosis of these patients. PMID- 4036737 TI - [Total cystectomy for urinary bladder cancer: clinicopathological study of 95 cases]. AB - Total cystectomy was performed on 95 patients with primary urinary bladder cancer between 1973 and 1983. Histopathological and prognostic studies were reviewed according to the general rules for clinical and pathological studies on bladder cancer. The cancer histological type were transitional cell carcinoma in 87 cases, squamous cell carcinoma in 5 cases, adenocarcinoma in 2 cases, and undifferentiated carcinoma in 1 case. The overall 5-year actuarial survival rate was 36.0%. As for the growth pattern of the bladder cancer, the 5-year survival rates for the patients with papillary non-invasive type (PNT), papillary invasive type (PIT), and non-papillary invasive type (NIT) were 100%, 25.8% and 34.8% respectively. As for the stage, the 5-year survival rates for the patients with pTa, pT1, pT2, pT3a, pT3b, and pT4 were 81.8%, 64.7%, 40.1%, 30.5%, 22.6% and 6.7% respectively. Of 87 patients with transitional cell carcinoma, the 5-year survival rates for the patients with grade 1, grade 2 and grade 3 were 100%, 43.0% and 32.1% respectively. Intramural lymphatic invasion and vascular invasion and intramural histopathological mode of spread were significant indicators of prognosis. PMID- 4036738 TI - [The use of dimethyl sulfoxide in the treatment of intractable urinary frequency]. AB - Intravesical instillation of dimethyl sulfoxide (DMSO) was used in the treatment of patients with intractable urinary frequency due to chronic prostatitis, chronic cystitis, tuberculous contracted bladder and interstitial cystitis. Before the application of this therapy, all 4 patients were examined carefully to rule out cases of acute infectious diseases of the urinary tract, active urinary tuberculosis, neurogenic bladder and carcinoma in situ of the bladder. Three of the four patients achieved an excellent response both subjectively and objectively. In the United States, intravesical instillation of DMSO had already been established as the specific method in the treatment of interstitial cystitis and no side effects have been reported so far. Therefore, we recommend the use of intravesical instillation of DMSO more commonly in various forms of intractable urinary frequency. PMID- 4036739 TI - [Clinical statistics on outpatients, inpatients and operations in 1983]. AB - Statistical studies on 1,990 outpatients, 574 inpatients and 606 operative procedures at our department in 1983 revealed the following. The most frequent diseases among the outpatients were urogenital infections followed by anomalies, tumors and stones. The major diseases among the inpatients were hypospadias, vesicoureteral reflux, congenital urethral stenosis, benign prostatic hypertrophy and bladder tumor. A total of 606 operations were performed on 559 patients, and the five major operations were hypospadias repair (80), TUR-P (54), optic internal urethrotomy (51), ureterocystoneostomy (40) and orchidopexy (34). PMID- 4036740 TI - [Transitional cell carcinoma of the renal pelvis with various histological appearances: a case report]. AB - A large left renal mass was removed from an 85-year-old male. Histological examination revealed various features: Anaplastic transitional cell carcinoma and glandular formation scattered with portions resembling cancer pearls. Sarcomatoid like area at ureteral margin of the mass and carcinoma-in-situ at renal pelvic mucosa were also seen. Final interpretation was grade III, transitional cell carcinoma, with squamous and glandular differentiation, spindling, and pleomorphic areas. PMID- 4036741 TI - [Synchronous tumors in right renal pelvis and left ureter]. AB - Bilateral synchronous urothelial tumors in the upper urinary tract seem to be rare. To our knowledge, only 34 cases have been reported previously. A 77-year old-man with the chief complaint of macrohematuria was admitted. Clinical investigations showed left ureteral and right renal pelvic tumors. Resection of the wall of the right renal pelvis and partial ureterectomy and its reanastomosis in the left ureter were done. Pathologic examination revealed that the right renal pelvic tumor was transitional cell carcinoma (G.2, pTlb), and the left ureteral tumor was invasive metaplastic epidermoid carcinoma. The patient is alive with no recurrence or metastasis 1 year after the operation. We reviewed all the reports of bilateral synchronous tumors we could find and discussed the histological findings and treatments reported. PMID- 4036742 TI - [Ectopic ureter without urinary incontinence despite ureteric orifice in the vestibulum: report of one case]. AB - This is one case of ectopic ureter which lacked urinary incontinence despite ureteric orifice in the vestibulum. CASE: A 20-year-old woman complained of miction pain. On examination, we found a small orifice in the vestibulum. DIP revealed slight hydronephrosis in the left contracted kidney and normal pyelogram in the right kidney. On cystoscopy, the bilateral ureteral orifices were normal, but we found the head of a catheter placed in the orifice of the vestibulum was passing under the mucosa of the bladder. The abnormal lumen was recognized by introducing an opaque medium through a catheter placed into the orifice of the vestibulum. The diagnosis was an abnormal left ureteral ectopic opening into the vestibulum with left complete duplication of renal pelvis and ureter. Left heminephro-ureterectomy was performed. Some discussions about the ectopic ureteral orifice without incontinence were conducted. PMID- 4036743 TI - [Clinical study of ureteral polyp: three cases report and review]. AB - Three cases of ureteral polyp are reported. The first case was an adult fibrous polyp. The second was the first report as a single, lower ureteral polyp in a child in Japan. The third was a granulomatous polyp accompanied by ureteral stones. About 130 cases of ureteral polyp have been reported in Japan. Although it has been classified into 4 to 7 histological types, the concept of ureteral polyp itself is confusing as its origin remains controversial. PMID- 4036744 TI - [Two cases of spontaneous fistula between urinary tract and gastrointestinal tract]. AB - This is a report of two cases of a fistula between the urinary and gastrointestinal tracts. One case was a 56-year-old female patient with a right pyeloduodenal fistula, and the other was a 38-year-old female with a left ureterodescending colon fistula. The chief complaint was right lumbago in the first case, and fever and left lumbago in the second case. Both cases were diagnosed by retrograde pyelography. In both cases, the ailing kidney appeared to be non-functioning, and the former was operated by nephrectomy, fistulectomy, and duodenectomy in the cuneate form, while the latter was operated by nephrectomy and fistulectomy. The cause of the formation of the fistula was considered to be chronic pyelonephritis accompanied by renal stones in the first case, and rupture of the colon diverticulitis in the second case. Postoperative prognosis was satisfactory in both cases. PMID- 4036745 TI - [A case of ectopia testis transversa]. AB - A case of ectopia testis transversa was reported. A patient, 35-year-old male, was admitted to our hospital with swelling of left scrotal contents. At operation, two testes were situated in the left scrotal half, but the right half was empty. Including our case, 66 cases of ectopia testis transversa have been reported in Japan. PMID- 4036746 TI - [Long-term administration of ceftriaxone (Ro 13-9904) to complicated urinary tract infections]. AB - The efficacy and safety of ceftriaxone (Ro 13-9904, CTRX) a new broad-spectrum semisynthetic cephalosporin with an outstanding long serum half-life, was evaluated in 22 patients with chronic complicated urinary tract infections. Although the overall clinical efficacy evaluated on day 5 and 10 were similar, the rate of excellent effectiveness was higher on day 10 than on day 5. Eighteen bacterial strains were cultured from freshly voided urine. Eighty percent of the bacteria were eradicated on day 5 and 86.2% were eradicated on day 10. Bacterial replacement had occurred in 3 cases on day 5 and in 6 cases on day 10. PMID- 4036747 TI - Karyotypes and morphological and histological alterations of the genital tracts of repeat breeder heifers with known breeding history. PMID- 4036748 TI - Antibody-dependent cell-mediated cytotoxicity in sheep. PMID- 4036749 TI - Enterotoxin production at 4, 22, and 37 degrees C by Yersinia enterocolitica and Yersinia enterocolitica-like bacteria isolated from porcine tonsils and pork products. PMID- 4036750 TI - Coloboma of the optic nerve head in Bengal tiger kittens (Panthera tigris tigris). PMID- 4036751 TI - Ammonia-like taint and creatine, creatinine and dimethylamine contents in reindeer meat. PMID- 4036752 TI - Long term studies on bone mineral changes during different lactations in Swedish dairy cattle. PMID- 4036753 TI - Isolation of thermophilic Campylobacters from Norwegian dogs and cats. PMID- 4036754 TI - Identification of thiamine diphosphate-binding proteins from rat liver supernatant. AB - Transketolase (EC 2.2.1.1) was shown to be the sole enzyme protein bound to thiamine diphosphate (ThDP) as coenzyme in the soluble fraction of rat liver. No new ThDP-binding proteins with the molar ratio of ThDP to protein of 1.0 were detected in the rat liver supernatant under the purification and assay conditions employed. PMID- 4036755 TI - Effects of vitamin C intake on whole blood plasma, leucocyte and urine ascorbic acid and urine oxalic acid levels. AB - Fifty volunteers among the students of the Faculty of Pharmacy at Ankara and Gazi Universities were taken 2 grams of Vitamin C per day at regular time intervals for two months. Blood and urine samples were collected in the beginning, one month and 2 months after vitamin administration. The whole blood, plasma and leucocyte ascorbic acid levels were increased after one and 2 months treatment. The urine ascorbic acid were also increased significantly. Urine oxalic acid were not elevated after vitamin C intake. PMID- 4036756 TI - Ascorbic acid effect on some lipid fractions in human beings. AB - A group of 50 volunteers of our Faculty students have taken Vitamin C 2 g per day at regular time intervals for 2 months. Blood samples were taken in the beginning, one month and 2 months after vitamin administration. Cholesterol, HDL cholesterol, lipoprotein and triglyceride concentrations were determined. Cholesterol concentrations were decreased significantly at the end of treatment. Triglyceride concentrations were decreased also in first and second month. HDL cholesterol were rised significantly and alpha and beta fractions of lipoprotein were increased. PMID- 4036757 TI - Effectiveness and reliability of medium term treatment with a diet rich in olive oil of patients with vascular diseases. AB - In the present work we investigated the usefulness of olive oil in a standard hypolipidemic diet suitable for the secondary prevention of atherosclerosis. Some patients who had received a diet with a P/S value of 1.3 were turned to a diet, rich in olive oil, with a P/S ratio of 0.52; the same number of patients were fed on with the initial diet. The main differences we found were a decrease of LDL cholesterol parallel to an increase of HDL cholesterol in the patients fed on the diet rich in olive oil. No modifications were found in these patients as far as hemostatic function and liver functional tests are concerned. PMID- 4036758 TI - 1-Alpha-OH-cholecalciferol (1-alpha-OH-D3) and optimal calcium intake in calcium deficiency osteoporosis mediated by parathyroid activity morphologic and biochemical changes in adult male rats. AB - By feeding adult male rats a calcium deficient diet for a period of 6 weeks osteoporosis can be induced with respect to significant changes in mass, turnover, chemical composition, and morphology of bone and parathyroid glands. When subsequently treating the osteoporotic rats with a combination of 1-alpha-OH cholecalciferol (1-alpha-OH-D3) and optimal calcium intake osteoporosis as well as morphologic changes of parathyroids can be almost totally reversed as soon as after 2 weeks and completely after 4 and 6 weeks. Notwithstanding the change to an optimal calcium intake seems to be more important in normalizing the osteoporotic skeleton resulting from calcium deficiency than is the ingestion of 1-alpha-OH-D3, which may per se induce new bone formation. PMID- 4036759 TI - Does the non-absorbable fat, (sucrose polyester), interfere with the intestinal absorption of vitamin A? AB - Sucrose polyester (SPE) is a synthetic non-absorbable lipid. The effect of SPE on vitamin A absorption was determined by monitoring the disappearance rate of radio labeled vitamin A from the jejunal perfusate of the rat. The relative distribution of radio-labeled vitamin A between the micellar phase and the perfusate containing SPE was determined. With SPE concentrations of 5, 10 and 20 g/l, vitamin A was concentrated in the SPE phase over the micellar phase by a factor of 4.4, 9.4, 19.8 respectively. Thus, vitamin A favored the SPE phase over the micellar phase in the distribution analysis. In vivo absorption experiments with SPE and non-SPE perfusates showed decreased net vitamin A absorption rates in the presence of SPE by 8.7% Thus, dietary ingestion of SPE results in some impairment of intestinal absorption of vitamin A, and may require vitamin A supplementation. PMID- 4036760 TI - Biochemical and clinical effects of vitamin E administration in homozygous beta thalassemia. AB - In beta-thalassemic homozygotes, low plasma levels of tocopherols may induce a red blood cell (RBC) lipid peroxidation and consequent hemolysis. This is an indication to treat these patients with vitamin E. In this study 26 beta thalassemic homozygotes aged 2-14 years, were given vitamin E, 10 orally and 16 parenterally, 300 mg per day for 15 days. Prior to administration and blood transfusion, as compared to normal subjects of the same age, plasma and RBC tocopherols were significantly lower, whereas RBC malonyldialdehyde (MDA) was significantly increased. In both groups, after tocopherol administration, an increase in plasma and RBC tocopherols and a decrease in RBC MDA were found. The significance of these variations was greater in the parenterally treated group than in orally treated group. The treatment with vitamin E, appears to be effective to reduce the RBC oxidative damage in homozygous beta-thalassemia, principally when administered parenterally perhaps because of its poor intestinal absorption in these subjects. PMID- 4036761 TI - Role of free radical scavengers on phenylhydrazine induced hemolysis in rat. AB - The mechanism of the phenylhydrazine induced oxidative hemolysis was studied on the point of role of the free radical scavengers in rats. Phenylhydrazine resulted in the degradation of hemoglobin and the lipid peroxidation of the erythrocyte membrane. Otherwise, the elevation of coenzyme Q9, endogenous CoQ in rats, levels in plasma was observed against the phenylhydrazine induced oxidative stress. Supplementation of coenzyme Q10, exogenous CoQ in rats, inhibited the phenylhydrazine induced hemolysis according to the suppression of both the degradation of hemoglobin and the lipid peroxidation of the erythrocyte membrane. These results suggest that free radical scavengers such as coenzyme Q9 and coenzyme Q10 have important roles on the phenylhydrazine induced hemolysis in rats. PMID- 4036762 TI - Tryptophan metabolism in patients with breast cancer. AB - Plasma levels of total tryptophan were significantly lower in 51 patients with breast cancer than in 14 women with benign breast cancer following surgery and after 12 weeks. The urinary excretion of xanthurenic and 5-hydroxyindoleacetic acids were similar in patients with cancer and benign disease but the excretion of N'-methylnicotinamide (NMN) was significantly higher (P less than 0.001) in the cancer patients. It is suggested that the elevated urinary excretions of NMN is due to higher NAD activity reflecting elevated glycolysis through the Cori cycle. PMID- 4036763 TI - Cytologic and biochemical changes in pulmonary washings of guinea pigs exposed to kerosene. AB - Guinea pigs were exposed to kerosene aerosol and compared to controls exposed to atmospheric air. Kerosene exposure induced cytologic and biochemical changes in the pulmonary washings of guinea pigs. Our results suggest that in chronic exposure to kerosene lung washings can be used as a rapid screening tool to detect the inflammatory response in the lungs. PMID- 4036764 TI - [Immediate hypersensitivity to fruits and vegetables and pollenosis]. AB - Various works have been published, mainly by Scandinavian authors, in which a partial immunological identity has been found to exist between birch pollen and hazelnut and apple. However, our attention has been particularly drawn to the high proportion of people who are allergic to the apple and other fruits, which in some cases has been as much as 50 and 70%, and in whom an oral pruritus alone is considered sufficient a symptom of allergies to certain foodstuffs. However due to the fact that the incidence of allergies to fruit in patients who suffer from pollen-related allergies is much lower in this area, being in the order of 7%, and because of the absence of birch, we decided to carry out our investigation in the opposite direction to that chosen by the Scandinavian researchers. That is to say, from the point of view of patients suffering from allergies to fruits and vegetables (these being the foodstuffs which most frequently produce allergic reactions in our own particular environment) we decided to investigate: 1) which foodstuffs, according to clinical history, are most frequently responsible for producing allergies; 2) their possible co existence with pollen related allergies; 3) which pollens are responsible for producing a higher rate of positive results in patients; 4) and finally, by means of the RAST inhibition technique, to discover it a cross-reactivity might exist between these pollens and the peanut or the pea. We chose 40 patients (19 females and 21 males), between the ages of 5 and 49 years old, whose clinical history showed beyond a shadow of a doubt that they displayed symptoms of immediate hypersensitivity after the ingestion of certain fruits and/or vegetables. The technique employed in the skin tests was that of scratch of the skin from the backs of the patients (in a prone position), systematically using fresh natural foodstuffs, and at the same time trying to ensure that they were of the same type as those that had originally produced the above-mentioned symptoms in the patients. On 193 occasions we carried out passive transfers (the Prausnitz Kustner method or P.K.), and on 13 patients we carried out oral provocative tests (cases with positive scratch and uncertain clinical histories). With regard to the pollens, we used glycerine-based antigens of the type: Lolium perenne, Olea europeae, Artemisia vulgaris and Parietaria officinalis of Dome/Hollister-Stier, and the Bencard gramineae.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 4036765 TI - [The growth curve in asthmatic children]. AB - The growth of 209 children with moderate and severe bronchial asthma seen at two different Health Care Centers for Bronchial Asthma Patients: (ICr and USP) was studied. The two groups differ mainly in socioeconomic level. Age at the onset of the disease, as well as duration and severity of the illness were considered. The first manifestations of the disease occurred before two years of age in 68.4% of the children. There was a predominance of males over females, with an almost 2:1 ratio in severe cases. The relationship between socioeconomic level and severity of the disease was highly significant (p less than 0.002). Weight and height were predominantly in the 50 percentile or below. This predominance was more evident for height. The height percentiles were significantly lower for the ICr group (p less than 0.01). Only 5.7% of the population studied had been submitted to prolonged (more than 3 months) corticoid treatment. PMID- 4036766 TI - Effects of kerosene on airway sensitization to egg albumin in guinea pig. AB - We undertook a study to determine if pre-exposure to kerosene smoke enhances airway sensitization to egg albumin in the guinea pig. Kerosene vapor inhalation for 15 days, 1 hour daily, in similar conditions to which some housewives who use kerosene as cooking fuel are exposed elicited tracheal damage characterized by signs of dysplasia and inflammatory infiltrate. When these animals were exposed to egg albumin aerosol there was an increase in the antialbumin antibody blood titer and an increased response to egg albumin in the isolated tracheal preparation (Schultz-Dale reaction), We conclude that the airway damage elicited by inhalation of kerosene vapor increase antigen absorption and thereby antibody formation. PMID- 4036767 TI - Today's Alabama medical student. PMID- 4036768 TI - Health and illness as perceived by the Black Carib Indians of Central America. PMID- 4036769 TI - Bile peritonitis. PMID- 4036771 TI - Myositis ossificans. PMID- 4036770 TI - Propoxyphene dependence and withdrawal. AB - Despite the widespread use of propoxyphene products as analgesics, there is no profile of a typical abuser of propoxyphene. Propoxyphene is structurally related to methadone and has central nervous system effects similar to those of opioids. The patient with dependence needs professional help in withdrawing from propoxyphene, in finding an alternative regimen for management of pain and in connecting with self-help programs focusing on life without chemical dependence. PMID- 4036772 TI - Harmful effects of indoor tanning. AB - The new indoor tanning units use predominantly ultraviolet A radiation, which has less potential than ultraviolet B for causing acute sunburn but more potential for photosensitivity reactions. Effects of long-term exposure to ultraviolet A may include dermal degenerative changes and predisposition skin cancer. PMID- 4036774 TI - Vitamin A and alcoholism. PMID- 4036773 TI - Treatment of helminthic diseases. PMID- 4036775 TI - A perspective on corporatization. PMID- 4036776 TI - Smoking responsibly? PMID- 4036777 TI - Vaginal delivery after cesarean section. PMID- 4036779 TI - Asymptomatic transient ST changes during ambulatory ECG monitoring in diabetic patients. AB - The reported higher incidence of painless myocardial infarction in diabetic patients suggests that asymptomatic transient myocardial ischemia may also be frequent in diabetes. To explore this possibility 51 subjects with type II diabetes, aged 43 to 71 years (mean +/- SEM 56 +/- 8), 70 nondiabetic patients with coronary artery disease (mean age 55 +/- 5), and 40 nondiabetic patients without overt coronary disease (age 54 +/- 9) were studied. Thirty-eight of the 51 diabetic patients (74%) had evidence of associated coronary disease and 19 (37%) had evidence of previous myocardial infarction. All subjects underwent continuous 24-hour ambulatory ECG monitoring. In 18 of 51 diabetic patients 93 episodes (73% of the total number) of asymptomatic ST segment changes were recorded; the total number of symptomatic episodes was 36, and they were observed in seven patients (27%). Forty-eight (60%) asymptomatic and 32 symptomatic episodes of significant ST changes were found in nondiabetic patients with coronary artery disease. When patients with previous myocardial infarction were examined separately, asymptomatic episodes of significant ST changes were observed in 10 of 19 diabetic patients and in 5 of 25 nondiabetic patients with coronary artery disease (p less than 0.05). In an additional 28 diabetic patients who underwent exercise stress test, 15 exhibited an abnormal ECG response; however, only five of them (33%) were symptomatic. This study suggests that the incidence of transitory myocardial ischemia, as assessed by ambulatory ECG monitoring and exercise stress test, is higher in type II diabetic patients than in nondiabetic control subjects with coronary artery disease. PMID- 4036778 TI - Reduction in type A behavior in healthy middle-aged American military officers. AB - One hundred eighteen senior officer-students of the U.S. Army War College who were healthy but exhibited type A behavior volunteered to be randomly selected and enrolled into (1) a section of 62 officers who received group type A behavior counseling for 9 months and (2) a control section of 56 officers who received no counseling of any kind. Marked or profound reduction in type A behavior at the end of 9 months was observed in 41.9% of the 62 participants who initially were enrolled to receive type A counseling; marked or profound reduction in type A behavior, however, was observed in only 8.9% of the 56 initially enrolled control subjects. No adverse effects on the military leadership qualities of type A counseled participants were observed by their classmates. Serum total cholesterol and plasma high-density lipoprotein (HDL) cholesterol measurements were obtained monthly. The serum cholesterol of the total cohort of subjects rose significantly during a month of considerable emotional tension and stress. Those subjects who underwent a profound reduction in the intensity of their type A behavior pattern also exhibited a significantly lower serum cholesterol value as the study continued than those subjects who exhibited no change in their type A behavior. No significant changes in plasma HDL cholesterol concentrations were observed in the total cohort during the above-mentioned period of stress, nor were any differences in this particular measurement noted between the type A counseled and the control participants. PMID- 4036780 TI - Smoking status at the time of acute myocardial infarction and subsequent prognosis. AB - A population of 2955 patients admitted to the hospital with acute myocardial infarction (AMI) was followed for 1 year after AMI or until death. Smokers as compared to nonsmokers were over 10 years younger (p less than 0.001) and had a lower prevalence of hypertension (p less than 0.01), congestive heart failure (p less than 0.0001), angina pectoris (p less than 0.01), and diabetes (p less than 0.0001). They had less severe myocardial infarction evidenced, for example, by lower prevalence of pulmonary congestion on chest x-ray (p less than 0.01). Both early (1 month) and late (6 and 12 months) mortality rates were lower in the smoking population (p less than 0.0001 at 1 month, p less than 0.05 at 6 months, and p less than 0.01 at 1 year). Adjusting for age and other variables reduced but did not reverse the survival differential favoring smokers at 1 month, but adjusting for age alone eliminated the differences in mortality rates at 6 and 12 months. We conclude that while smoking is a risk factor for cardiovascular disease and may contribute to the occurrence of AMI at a younger age, smoking at the time of AMI does not appear to be an independent predictor of death during the first year after AMI. PMID- 4036781 TI - Quantitation of regional left ventricular function by two-dimensional echocardiography in normals and patients with coronary artery disease. AB - Regional endocardial motion and wall thickening of the left ventricle were quantitatively assessed in nine normal subjects and in 21 patients with coronary artery disease using two-dimensional echocardiography (2DE) and a computerized light pen system. Eight equal sectors of a cross-sectional image from parasternal short-axis, apical four-and two-chamber views were used for measuring sector area difference of endocardial motion and wall thickness between end diastole and end systole. In 13 patients with anterior wall motion abnormalities, area difference of wall thickening found by 2DE was abnormal in 12 of 13 (92%) patients, and only in 6 of 13 (46%) patients by endocardial motion. In 10 patients with dyskinetic regions in apex or anterior wall, dyskinesia by wall thickening was found in all patients, but only in 6 of 10 (60%) by endocardial motion. Thus, wall thickening assessed by 2DE is a more sensitive technique than analysis of endocardial motion in evaluating regional wall motion abnormalities in patients with coronary artery disease. PMID- 4036782 TI - Unidirectional retrograde atrioventricular nodal block in man: determinants of reversibility by vagal antagonism. AB - The mechanism of unidirectional retrograde atrioventricular (AV) nodal block remains largely unknown. In this study, factors determining the reversal of the unidirectional block by atropine were evaluated in 12 patients who had no demonstrable ventriculoatrial (VA) conduction during ventricular pacing. Six patients demonstrated 1:1 VA conduction after atropine (group I), while the remaining six patients continued to show VA block (group II). During the control study there was no significant difference in the sinus cycle length and AH interval between the two groups. The percent decrease in sinus cycle length after atropine was also similar in groups I and II (i.e., 23 +/- 12 and 26 +/- 6, respectively). The effect on antegrade AV nodal conduction (i.e., the percent decrease in AH interval), however, was significantly greater in group I (24 +/- 9) as compared to group II (9 +/- 5) (p less than 0.004). The onset of VA conduction appeared to correlate with the improvement of antegrade conduction. The ratio of these two effects of atropine (i.e., percent decrease in AH interval to percent decrease in sinus cycle length) was higher when VA conduction was first demonstrated in group I (2.3 +/- 1.1) than at the maximal effect of atropine (1.2 +/- 0.3), reflecting a relatively greater decrease in sinus cycle length. Three of six group I patients redeveloped VA block at maximal effect of atropine. The results suggest a functional and dynamic nature of the unidirectional AV nodal block, possibly caused by vagal influence exaggerating the well-known directional asymmetry of AV nodal conduction in man.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4036783 TI - Programmable extrastimulus pacing for long-term management of supraventricular and ventricular tachycardias: clinical experience in 16 patients. AB - Sixteen patients with recurrent, drug-resistant supraventricular (13 patients) or ventricular (3 patients) tachycardia were treated chronically by programmable extrastimulus pacing; either a fully automatic device (Telectronics PASAR 4151: eight patients with supraventricular tachycardia) or a patient--activated device (Medtronic Interactive Tachy System) was used. During a follow-up period of 5 to 30 months, five of the subjects treated with the fully automatic device showed successful results, one had recurrent tachycardia, and two had their units explanted for system-related problems. The patients treated with the externally activated device were, on the whole, very well controlled. This mode of treatment, if applied in well-selected cases, is promising; it seems safe and considerably reduces the number of hospital admissions. PMID- 4036784 TI - Alterations in the distribution of high-energy phosphates during ischemia in a canine model of reperfusion-induced ventricular fibrillation. AB - High-energy phosphate metabolites of the canine heart were analyzed before coronary artery occlusion and after 15 minutes of ischemia, and the results were then correlated with the occurrence of ventricular fibrillation upon reperfusion (RVF). Animals which developed VF upon reperfusion after 15 minutes of ischemia had lower levels of creatine phosphate and endocardial adenosine triphosphate (ATP), and increased accumulation of the catabolites of ATP metabolism, inosine and hypoxanthine. Animals which developed RVF also had lower levels of regional myocardial blood flow in the center of the ischemic zone during the period of coronary occlusion. Occluded bed size was the same in dogs which did and did not develop RVF. These data suggest that VF upon reflow is associated with more severe ischemia and an increase in high-energy phosphate catabolism during the period of ischemia. PMID- 4036785 TI - Ventricular function in transposition of the great arteries: evaluation by radionuclide angiocardiography. AB - Right ventricular ejection fraction and tricuspid regurgitation were estimated by radionuclide angiocardiography to quantitate systemic ventricular function in "simple" transposition of the great arteries. Mean right ventricular ejection fraction was 0.52 +/- 0.07 for 18 pre Mustard operation infants, 0.54 +/- 0.07 for 23 patients operated upon less than a 1 year before, and 0.57 +/- 0.08 for 14 patients operated upon more than 3 years earlier. Eight patients were evaluated before and following the Mustard operation; ejection fraction rose in three, fell in three, and remained constant in two. Mean right ventricular ejection fraction was not different between groups nor when compared to our "normal." The left ventricle:right ventricle stroke volume ratio of the postoperative patients was compatible with tricuspid regurgitation in four patients. This radionuclide study suggests that following surgery for transposition of the great arteries: mean right ventricular systolic ejection fraction remains at levels consistent with values usually found for the "normal" right ventricle; group right ventricular function does not deteriorate in the years following surgery; and tricuspid regurgitation may be detected in the early postoperative years. PMID- 4036786 TI - Absence of myocardial biochemical toxicity with a nonionic contrast agent (iopamidol). AB - To evaluate the myocardial metabolic effects of a new nonionic contrast agent, iopamidol, a randomized, double-blind study was performed comparing iopamidol with sodium meglumine diatrizoate (Renografin-76) in 23 patients with ischemic heart disease. Coronary sinus and arterial metabolic samples were obtained prior to and during the 20-minute period following the contrast left ventriculogram. Ten patients received iopamidol and 13 received Renografin-76. The chemical lactate extraction in the iopamidol group was 13 +/- 9% prior to left ventriculography and 17 +/- 12% following the contrast injection (p less than 0.005). In the Renografin-76 group, the lactate extraction was 23 +/- 13% and decreased significantly to 12 +/- 24% following the ventriculogram (p less than 0.01). In a subset of these patients (n = 10), [1-(14)C] lactate was infused as a tracer to quantitate the amount of lactate released by the myocardium. [1-(14)C] lactate analysis demonstrated that the fall in lactate extraction ratio following Renografin-76 was due to an increase in myocardial lactate release. In the Renografin-76 group there was a 53 +/- 37% increase in lactate release at 10 minutes after contrast agent injection (p less than 0.005), while in the iopamidol patients there was no significant change in lactate release following contrast ventriculography. The increase in lactate release in the Renografin-76 group suggests that myocardial ischemia is induced with this ionic contrast agent. In comparison, the nonionic contrast agent is less toxic to the myocardium and is not associated with the biochemical changes of cellular ischemia. PMID- 4036787 TI - Changes in left ventricular diastolic function after left ventriculography: a comparison with iopamidol and urografin. AB - Changes in left ventricular (LV) diastolic indices after left ventriculography (LVG) with iopamidol or urografin were studied in 42 subjects. Increase in heart rate and decrease in LV systolic pressure were more significant with urografin than with iopamidol (p less than 0.05 to 0.001). LV end-diastolic pressure was elevated more with urografin than with iopamidol (p less than 0.005 to 0.05) 1 to 3 minutes after LVG. LV peak negative dP/dt decreased significantly with urografin immediately (10 to 15 seconds, -511 and 30 seconds, -376 mm Hg/sec; p less than 0.0005 to 0.02), but with iopamidol it did not decrease significantly after LVG. Time constant, T, was elongated with iopamidol (10 to 15 seconds, +13 and 30 seconds, +6 msec; p less than 0.0005), but this elongation was significantly less than urografin (10 to 15 seconds, +34; 30 seconds, +25; 1 minute, +15; and 2 minutes, +10 msec; p less than 0.05 to 0.0005). We conclude that iopamidol disturbed LV diastolic function to a lesser degree than did urografin. PMID- 4036788 TI - Effect of acute standing and prolonged upright activity on left ventricular hemodynamics, systolic and diastolic intervals, and QT-QS2 relationship. AB - It is generally accepted that upright posture decreases preload and afterload, which could alter left ventricular (LV) performance. It is not known if changes occurring with acute standing persist after prolonged ambulatory activity (amb act). In seven normal subjects echocardiographic end-diastolic and end-systolic diameters, percent shortening of the internal diameter (% delta D) and end systolic wall stress (ES-WS), radionuclide diastolic volume and ejection fraction, preejection period over left ventricular ejection time (PEP/LVET), and diastolic time and QT-QS2 were measured supine, within 1 to 2 minutes after standing and after prolonged (60 minutes) amb-act. In addition, serial measurements were performed in PEP/LVET for 105 minutes at 15-minute intervals. With acute standing, end-diastolic diameter, diastolic volume, and ES-WS decreased (p less than 0.01); heart rate and PEP/LVET increased (p less than 0.01); while % delta D and ejection fraction remained unchanged. There was an inverse correlation between change in PEP/LVET and diastolic diameter (r = 0.59), but no correlation between PEP/LVET and ES-WS. The diastolic time per beat and per minute decreased (375 +/- 115 msec from 519 +/- 176 msec [p less than 0.01] and 31.3 +/- 4.2 sec/min from 33.7 +/- 4.5 sec/min [p less than 0.01]). The QT-QS2 increased when compared to supine (-7 +/- 7.6 msec from -22 +/- 7.7 msec [p less than 0.005]), but the QT-QS2 relationship remained normal (QT less than or equal to QS2). All the dynamic changes that occurred with acute standing tended to persist during prolonged amb-act. PMID- 4036789 TI - Risk factors and the incidence of hypertension in black physicians: the Meharry Cohort Study. AB - A prospective longitudinal study of black medical students was conducted to determine the predictive value of hypertension precursors. Follow-up examinations, averaging 22.5 years later, were performed on 341 subjects (78.8%); 25 (5.8%) additional subjects were identified as dead out of 433 original participants. Results are reported on 313 reexamined men. A remarkable 43.8% of the physicians had elevated blood pressure higher than 140/90 mm Hg or gave a history of hypertension and treatment. Correlation coefficients, quintile distributions, and regressions all confirmed the ability of baseline SBP and DBP to predict their respective pressures on follow-up examination. Discriminant function tests yielded baseline SBP, DBP, smoking, and parental history of stroke or hypertension to be the most significant precursors distinguishing hypertensive from normotensive groups, and the model correctly classified 69.7% of the subjects. Baseline cholesterol and Quetelet index levels did not reach statistical significance. The cold pressor test was not predictive but interim weight gain was highly significant. Results are discussed in relation to comparable studies on white populations. PMID- 4036790 TI - Mode of stimulation versus response: validation of a protocol for induction of ventricular tachycardia. AB - Electrophysiologic studies were prospectively performed in 91 consecutive patients referred for evaluation of sustained ventricular tachycardia or sudden cardiac death. Fifty-two patients had a history of sustained ventricular tachycardia and 39 patients had a history of sudden cardiac death. The identical stimulation protocol was used in all patients. The stepwise protocol involved atrial pacing, burst ventricular pacing, single, double, and triple extrastimuli during ventricular pacing. Stimulation was performed at the right ventricular apex at two and five times diastolic threshold. Using this protocol, ventricular tachycardia was inducible in 48 (92%) of the 52 patients with a history of sustained ventricular tachycardia and in 28 (72%) of 39 patients with a history of sudden cardiac death (p less than 0.02). The use of a third extrastimulus increased the yield of inducible ventricular tachycardia by 37% in patients with a history of sustained ventricular tachycardia and by 25% in patients with a history of sudden cardiac death. Stimulation at five times diastolic threshold and stimulation from the right ventricular outflow tract added a 15% increment in overall yield of inducible ventricular tachycardia in patients with a history of sustained ventricular tachycardia, and a 26% increment in yield in patients with a history of sudden cardiac death. Forty-four (92%) of the 48 inducible patients in the sustained ventricular tachycardia group had inducible monomorphic ventricular tachycardia as compared to 19 (68%) of 28 patients in the sudden cardiac death group (p less than 0.02).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4036791 TI - Rapid atrial pacing-induced infra-His conduction block in children. AB - High right atrial pacing (abrupt initiation and random coupling to the spontaneous rhythm) was performed in 285 pediatric cardiac patients for diagnostic purposes. Nine patients (3%) were found to have pacing-induced infra His conduction block. In two patients this occurred following a preceding long cycle as well as a preceding short-to-long sequence cycle length change. In five patients block occurred with an abrupt shortening of the coupling H-H interval (in three patients the infra-His block initiated a series of 2:1 infra-His block). In two patients with type II second-degree atrioventricular block the initiating events were not recorded. In one of them, when the rapid atrial pacing was incremented to the same cycle length with infra-His block, the atrioventricular response became 1:1 with normal conduction. These findings of pacing-induced infra-His conduction block can be explained by the normal response of the His-Purkinje system to changes in the preceding cycle lengths, and to the abrupt shortening of the coupling interval. PMID- 4036792 TI - Forward ejection fraction: a new index of left ventricular function in mitral regurgitation. AB - Previous studies have shown that a normal LVEF is not a reliable index of LV function in MR. We hypothesized that the forward EF, which is the forward stroke volume (measured by Fick or thermodilution) divided by end-diastolic volume (measured by contrast ventriculography) may be a useful index of LV function, since it represents LV emptying into the aorta. This index was examined in 54 patients with chronic MR who had normal EF (greater than or equal to 50%). There were significant correlations between the forward EF and the end-diastolic volume index (r = -0.69, p less than 0.001), end-systolic volume index (r = -0.64, p less than 0.001), cardiac index (r = 0.43, p less than 0.01), and the ratio of systolic pressure-to-end-systolic volume (r = 0.65, p less than 0.001). Patients were divided into two groups according to the forward EF: group I (n = 34) had forward EF less than or equal to 35%; and group II (n = 20) had forward EF greater than 35%. Of the 32 patients who subsequently underwent mitral valve replacement, 24 patients were in group I and eight patients were in group II. At a mean follow-up of 35 months, four patients died; all of them were in group I. Improvement in functional class occurred in 75% of surgical survivors (80% in group I and 63% in group II, p = NS). These preliminary data suggest that forward EF may be a useful index of LV performance in patients with MR who have normal EF. PMID- 4036793 TI - Clinically "silent" atrial septal defect: diagnosis by two-dimensional and Doppler echocardiography. PMID- 4036794 TI - Ventricular septal rupture following a clinically unrecognized myocardial infarction. PMID- 4036795 TI - Kawasaki disease complicated by acute myocardial infarction 9 years after onset. PMID- 4036796 TI - Angiographic diagnosis of inward flexion of porcine bioprosthetic valve stents. PMID- 4036797 TI - Aortic stenosis with linear calcification of ascending aorta. PMID- 4036798 TI - Esophageal electrocardiography using a balloon-tip electrode. PMID- 4036799 TI - Congenital isolated tricuspid regurgitation in an adult. PMID- 4036800 TI - The challenge of the future in pediatric cardiology. PMID- 4036801 TI - Cardiac cellular electrophysiologic actions of adenosine and adenosine triphosphate. PMID- 4036802 TI - Third party prescription programs: cost containment issues and strategies. PMID- 4036803 TI - A new way of thinking. PMID- 4036804 TI - Marketing your nonprescription drug department. PMID- 4036805 TI - Hydrocortisone. PMID- 4036806 TI - Job stress in pharmacy practice: implications for managers. PMID- 4036808 TI - Capital punishment and the responsible pharmacist. PMID- 4036807 TI - Pharmacists as speakers: getting started. PMID- 4036809 TI - NHBPEP updates statement on home blood pressure devices. PMID- 4036810 TI - Membership in the "new APhA': an investment in the future. PMID- 4036811 TI - Managing for change: mastering your environment. PMID- 4036812 TI - Inducing you to use generics: what third party programs are offering. PMID- 4036813 TI - Enhancing communication with elderly patients. PMID- 4036814 TI - Predictions on the future: what's ahead for pharmacy. PMID- 4036815 TI - Malignant arrhythmia in relation to serum potassium in acute myocardial infarction. AB - Several studies of patients with acute myocardial infarction have shown an association between hypokalemia, including mild hypokalemia, and increased occurrence of cardiac arrhythmia. Hypokalemia in acute myocardial infarction is significantly associated with diuretic therapy before or during the infarction. In a study of 1,074 patients with acute myocardial infarction, ventricular fibrillation occurred in 17.2% of 122 hypokalemic patients and in 7.5% of 952 normokalemic patients (p less than 0.01). The association of hypokalemia and ventricular fibrillation was not specifically related to poor left ventricular function. Recent studies indicate that hypokalemia is an independent risk factor of ventricular arrhythmia early in acute myocardial infarction, but a definite causal role of potassium remains to be shown. The importance of catecholamines versus serum potassium levels in occurrence of arrhythmia has not been clarified. PMID- 4036816 TI - Differentiation between acute and healed myocardial infarction by signal averaging and color encoding two-dimensional echocardiography. AB - To evaluate the ability of a system developed in our laboratory to differentiate between acute and healed myocardial infarction (MI), gated 2-dimensional echocardiography was performed in 10 patients with recent MI (within 48 hours) and 10 patients with healed MI (later than 4 weeks). The 2-dimensional echocardiographic images were digitized using a Datacube VG-120 videoframe digitizer and each digitized videoframe (320 X 240 matrix) was transmitted using a high-speed serial data link to a second computer and stored on floppy disc. Five gated video frames of each patient were time-averaged to give a smoothed digitized image. This image was displayed on high-resolution color monitor connected to a color graphic subsystem. Sixty-four colors indicated pixel intensity. The exact pixel value at any given location was determined using a high-resolution light pen. Color or pixel values were not significantly different between the area of acute MI (pixel intensity 23 +/- 3, mean +/- standard deviation) identified by a regional wall motion abnormality, and the adjacent normal muscle (23 +/- 4). In each patient with healed MI, an increase in color intensity and pixel value (43 +/- 6) was seen in the area of MI (i.e., area of regional wall motion abnormality) compared with adjacent normal muscle (23 +/- 2) (p less than 0.001). These preliminary data in selected patients indicate that this technique enables differentiation between acute and healed MI. It could be of value in management of patients with suspected MI. PMID- 4036817 TI - Effect of ventricular fibrillation complicating acute myocardial infarction on long-term prognosis: importance of the site of infarction. AB - Identification of high-risk subgroups of patients after acute myocardial infarction (AMI) is essential for evaluation of targeted preventive strategies. A case-control study was performed in 250 post-AMI patients to examine whether an episode of ventricular fibrillation (VF) during the in-hospital period modifies the long-term prognosis for patients with either an anterior or an inferior AMI. After identification of 70 patients with an anterior AMI and 55 patients with an inferior AMI, all complicated by VF and discharged alive, we selected 125 additional patients who had an AMI not complicated by VF (control subjects). To minimize the potential sources of differences in outcome, cases and controls were matched for the following variables: sex (all men), age (same +/- 2 years), coronary care unit (same), epoch of AMI (same +/- 3 months), and site of AMI (same). Left ventricular dysfunction and prior AMI were present in only a few patients. Patients receiving either acute or long-term treatment with beta adrenergic blocking agents were not included. The average follow up was 59 months (range 12 to 120). The cumulative mortality during the first 5 years for the patients with inferior AMI without VF (6%, 11%, 13%, 13% and 13%) was modest and not significantly different from that of inferior AMI complicated by VF (6%, 11%, 20%, 20%, and 26%). In contrast, a striking difference appeared when the cumulative mortality of patients with anterior AMI without VF (9%, 13%, 17%, 27%, and 29%) was compared with that of patients with anterior AMI complicated by VF (32%, 40%, 46%, 49% and 54%) (p less than 0.005).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4036818 TI - Coronary artery dilation and hemodynamic responses after isosorbide dinitrate therapy in patients with coronary artery disease. AB - The response to sublingual isosorbide dinitrate (ISDN) was studied in 10 men with suspected coronary artery disease undergoing coronary arteriography. A Swan-Ganz catheter was placed in the pulmonary artery to record hemodynamic response. Diseased coronary segments were identified during routine Judkins selective coronary angiograms. Sublingual isosorbide dinitrate (ISDN) (5 or 10 mg) was then given with the catheters in place. Multiple sequential single-view coronary angiograms and pulmonary and systemic hemodynamic responses were recorded over 30 minutes after drug administration. At 30 minutes, there was a 53% reduction (p less than 0.01) in pulmonary capillary wedge pressure and a 15% decrease (p less than 0.05) in systemic and pulmonary vascular resistance, with a net 13% decrease (p less than 0.01) in cardiac output and 20% decrease (p less than 0.01) in mean arterial pressure. Quantitative arteriography demonstrated substantial dilation of luminal cross-sectional area in both normal and diseased coronary arterial segments. Normal epicardial segments were grouped according to luminal area (1 to 4, 4 to 8 and more than 8 mm2) and demonstrated maximal area dilation at 10 minutes of 55% (p less than 0.01), 29% (p less than 0.01) and 16% (p less than 0.05), respectively. Diseased epicardial segments (stenosis 50% or greater) dilated 51% (p less than 0.01) at 10 minutes. Calculated stenosis resistance decreased 40% (p less than 0.01). Diseased segments in small and middle-sized arteries (1 to 8 mm2) are 4 times more reactive than those in larger arteries (more than 8 mm2), with peak dilation of 77 vs 21% (p less than 0.01) at 30 minutes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4036819 TI - Frequency of intracoronary filling defects by angiography in angina pectoris at rest. AB - Recent studies have shown that pain at rest in patients with unstable angina pectoris is often caused by transient reduction in regional myocardial perfusion. Coronary spasm has been implicated as a mechanism of this phenomenon. Recent reports have documented the occurrence of intracoronary thrombus in patients with unstable angina. Previous surveys have estimated a 6 to 12% frequency of intracoronary thrombus in this syndrome, but have not examined whether this incidence is related to how recent the angina at rest was. Angiograms of 119 patients with unstable angina who had rest pain within 14 days of angiography and 35 patients with stable angina were surveyed. Patients with unstable angina were subgrouped according to how recent angina at rest was at the time of angiography. Group I consisted of 44 patients in whom rest pain occurred within 24 hours before angiography. The 75 patients in group II had angina at rest between 1 and 14 days before angiography. Patients in group II had stable angina. The angiographic criterion for intracoronary thrombus was an intraluminal filling defect, surrounded by contrast medium on 3 sides, located just distal to or within a coronary stenosis, as assessed by each of 2 independent observers blinded to the nature of the anginal syndrome and its temporal proximity. Intracoronary thrombi were found in 44 of 119 patients with unstable angina (37%) and 0 of 35 patients with stable angina (p less than 0.00002). Intracoronary thrombi were found in 23 of 44 patients (52%) in group I and 21 of 75 (28%) in group II (p less than 0.008).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4036820 TI - Functional significance of transient collaterals during coronary artery spasm. AB - Coronary collateral vessels appear transiently during vasospasm. To examine the functional role of such collaterals in acute myocardial ischemia, regional coronary flow was determined in patients who showed isolated total spasm in the proximal left anterior descending coronary artery associated with (n = 7, group I) and without (n = 9, group II) collaterals, which were donated by the nonspastic right coronary artery during ergonovine provocative test. Aortic pressure and heart rate were not significantly different in the 2 groups before and during spasm. During vasospasm, the levels of pulmonary artery end-diastolic pressure were significantly higher in group II (19 +/- 2 mm Hg, mean +/- standard error) than in group I (15 +/- 1 mm Hg, p less than 0.05). Under these conditions, great cardiac vein flow (GCVF) measured by thermodilution was markedly reduced in group II (from 60 +/- 4 ml/min to 37 +/- 4 ml/min, p less than 0.01), whereas GCVF was slightly reduced in group I (from 56 +/- 4 ml/min to 51 +/- 4 ml/min), indicating that residual GCVF was greater in patients with than in those without collaterals (p less than 0.05). The calculated coronary collateral resistance index during vasospasm was significantly lower in group I (2.06 +/- 0.18 mm Hg min/ml) than in group II (2.91 +/- 0.30 mm Hg min/ml, p less than 0.05). Total left anterior descending coronary artery spasm with collaterals was less frequently associated with ST elevation in the precordial electrocardiogram recorded during spasm.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4036821 TI - Systemic, left ventricular and coronary hemodynamic effects of intravenous diltiazem in coronary artery disease. AB - Systemic and coronary hemodynamic effects of intravenous diltiazem, administered as a bolus of 250 micrograms/kg followed by an infusion of 1.4 micrograms/kg/min, were examined in 14 patients with effort angina. There was no change in heart rate despite significant decreases in systolic, diastolic and mean systemic pressures (13%, 10% and 11%, respectively, all p less than 0.01). The blood pressure decrease was closely correlated with the initial blood pressure (r = 0.81, p less than 0.05). Neither left ventricular end-diastolic pressure nor peak dP/dt changed significantly, but peripheral vascular resistance decreased 16% (p less than 0.001) and stroke volume index increased 10% (p less than 0.05). The pressure-rate product decreased 15% (p less than 0.005), but coronary blood flow was maintained as coronary resistance decreased 14% (p less than 0.025). Diltiazem increased regional coronary flow in some patients. Thus, intravenous diltiazem dilates coronary and systemic resistance vessels, without an increase in heart rate, favorably altering indexes of myocardial oxygen supply and demand. PMID- 4036822 TI - Correlation of the exercise ST/HR slope with anatomic and radionuclide cineangiographic findings in stable angina pectoris. AB - A rate-related change in ST-segment depression with exercise (ST/HR slope) of 6.0 microV/beat/min or more has been proposed as an accurate predictor of 3-vessel coronary artery disease (CAD). To further assess the accuracy and functional correlates of this method, exercise electrocardiograms were compared with radionuclide rest and exercise left ventricular (LV) ejection fraction (EF) and angiography in 35 patients with stable angina. The ST/HR slope was significantly increased in patients with 3-vessel CAD. An ST/HR slope of 6.0 or more identified 3-vessel CAD with a sensitivity of 89% and specificity of 88%. The predictive value for 3-vessel CAD was 73% owing to the presence of 3 false-positive slopes. The patients from whom these slopes were derived had functionally severe 2-vessel CAD, with an average decrease in exercise LVEF of 13%. Two of these 3 had additional left main CAD and the third has unsuspected additional aortic regurgitation. For the entire group, the exercise ST/HR slope was linearly related to the exercise change in LVEF (r = -0.55, p less than 0.001). Mean exercise change in LVEF for stable angina patients with ST/HR slopes of 4.5 or more was significantly different from that for patients with lower ST/HR slopes ( 12 +/- 1% vs + 2 +/- 2%, p less than 0.0001). Thus, the ST/HR slope is both sensitive and specific for the identification of 3-vessel CAD, and high ST/HR slopes in patients with less extensive anatomic disease may predict functionally severe ischemia. PMID- 4036823 TI - Left ventricular thrombi diagnosed by echocardiography in patients with acute myocardial infarction treated with intracoronary streptokinase followed by intravenous heparin. AB - Thirty patients with acute myocardial infarction (AMI) treated with intracoronary streptokinase (7 X 10(5) +/- 3 X 10(5) IU) followed by 10 days of intravenous heparin (800 to 1,500 IU/hour) therapy were prospectively studied by serial 2 dimensional echocardiography for left ventricular (LV) thrombus. Within the first 24 hours, evidence of a thrombolytic state appeared as indicated by fibrin and fibrinogen degradation products (123 +/- 45 mg/dl at 24 hours). Throughout the course of this study partial thromboplastin times were maintained within therapeutic range (40 to 100 seconds). Apical LV thrombus developed in 8 of 30 patients (27%). Apical thrombus developed within 24 hours in 3 patients with anterior AMI and persisted through day 10. By day 10, apical thrombus developed in 3 additional patients with anterior AMI and 2 patients with inferior AMI. In these patients, anterior AMI and apical dysfunction were significant (p less than 0.01 for both) determinants of LV thrombus formation. Hence, the incidence of LV thrombus in patients treated with streptokinase/heparin is similar to that reported earlier in comparable patients not receiving thrombolytic therapy. PMID- 4036824 TI - Relation of effectiveness of intracoronary thrombolysis in acute myocardial infarction to systemic thrombolytic state. AB - Twenty-nine patients received intracoronary thrombolytic therapy for acute myocardial infarction 3.5 +/- 1.4 hours (mean +/- standard deviation) after the onset of pain. Ten patients received urokinase (UK) and 19 patients received streptokinase (SK). Laboratory variables of the coagulation system were measured before and immediately after therapy. When comparing patients in whom coronary artery recanalization occurred vs those in whom the artery remained occluded, those in whom recanalization was achieved had greater alterations in fibrinogen, prothrombin time, activated partial thromboplastin time, fibrin/fibrinogen degradation products and plasminogen by thrombolytic therapy than did those in whom recanalization was not achieved (p less than 0.05 for all variables). Euglobulin lysis time showed a similar but nonsignificant trend (p = 0.114). Patients who received SK showed markedly greater alterations in coagulation parameters than did patients treated with UK (p less than 0.05 for 5 of 6 variables measured) and had a much higher incidence of successful thrombolysis (74% for SK, 20% for UK). These data indicate that the development of a systemic fibrinolytic state contributes to success when using intracoronary thrombolytic agents in acute myocardial infarction. Rather than being considered an adverse effect of therapy, a systemic lytic state may serve as a reasonable clinical goal in attempting to produce thrombolysis. PMID- 4036825 TI - Continuous determination of regional myocardial blood flow with intracoronary krypton-81m in coronary artery disease. AB - Pacing-induced changes in regional coronary flow were studied continuously with krypton-81m by intracoronary infusion in 25 patients: 21 with 50% or greater diameter narrowing of 1 or more left coronary arteries (group I) and 4 with less than 50% diameter reduction of a left coronary artery (group II). No changes occurred in group II. In group I, krypton-81m perfusion decreased progressively in all areas with more than 70% diameter narrowing, with a simultaneous increase in normal regions. At the end of pacing during angina, krypton-81m perfusion was reduced to 81 +/- 4% of control in areas with 71 to 90% diameter reduction (n = 8) and to 69 +/- 6% in areas with more than 90% diameter narrowing (n = 15). In contrast, in regions with 50 to 70% diameter reduction changes were variable (decrease in 4 regions, increase in 2 and an unchanged distribution in 1 region). Krypton-81m perfusion decreased early, before general signs of ischemia in areas with more than 90% diameter reduction, whereas this decrease occurred later in regions with 71 to 90% diameter narrowing, concurrently with ST-segment changes but before anginal pain. Although all signs of ischemia had disappeared between 2 and 5 minutes after pacing, changes in krypton-81m distribution persisted in most areas for 5 to 15 minutes after pacing. It is concluded that the functional significance of coronary arterial narrowing can be assessed with a continuous intracoronary infusion of krypton-81m. Changes in regional distribution persisted after cessation of pacing-induced ischemia, indicating an ongoing decrease in regional myocardial blood flow. PMID- 4036826 TI - Dipyridamole-echocardiography test in effort angina pectoris. AB - This study assesses the clinical feasibility and usefulness of dipyridamole infusion for the detection of coronary artery disease (CAD) by using 2 dimensional echocardiography (2-D echo) and 12-lead electrocardiographic monitoring. Dipyridamole infusion (0.14 mg/kg/min for 4 minutes) was performed in 66 consecutive patients with effort chest pain and in 9 control subjects. Among the 28 patients with positive dipyridamole-echocardiography test responses, 18 had diagnostic electrocardiographic changes (ST-segment depression on anterolateral leads), but these changes were unrelated to the site of asynergy. The dipyridamole-echocardiography test had an overall sensitivity of 56% and specificity of 100% for the presence of CAD. Exercise stress testing (EST) had an overall sensitivity of 62% and a specificity of 80%. Thus, the dipyridamole echocardiography test, which is feasible in essentially all patients with good basal echocardiograms, has a lower overall sensitivity in detecting CAD than EST but a higher specificity, detects the site of apparent ischemia as identified by regional asynergy more precisely than EST, and can unmask electrocardiographically silent effort ischemia. PMID- 4036827 TI - Coronary sinus occlusion pressure and its relation to intracardiac pressure. AB - The hemodynamic components of coronary sinus (CS) occlusion pressure in humans have not been well described. If no other outflow for venous blood were present, then after acute occlusion of the coronary sinus the pressure would increase and equal aortic pressure. However, if thebesian vein drainage between the left ventricle and the coronary veins has an important role in humans, then CS occlusion pressure might reflect left ventricular (LV) pressure through transmitted LV pressure or intramyocardial pressure. To study this relation, 27 patients who underwent routine diagnostic cardiac catheterization were evaluated. Occlusion was accomplished by sudden inflation of a No. 7Fr balloon-tipped catheter placed into the CS. LV end-diastolic pressure and end-diastolic CS occlusion pressure were simultaneously recorded at rest. LV end-diastolic pressure (16.7 +/- 5.6 mm Hg) was not significantly different from end-diastolic CS occlusion pressure (15.9 +/- 5.4 mm Hg). LV end-diastolic and end-diastolic CS occlusion pressures were positively correlated (p less than 0.001) over the entire range of pressures (9 to 27 mm Hg). In contrast, systolic CS occlusion pressure was significantly lower than LV systolic pressure and unrelated to right sided heart pressures. It is concluded that in humans, end-diastolic CS occlusion pressure closely parallels LV end-diastolic pressure, and measurement of CS occlusion pressure to assess LV end-diastolic pressure may have clinical use. These findings also suggest the existence of hemodynamically important thebesian vessel connections that may have implications for retroperfusion or pressure controlled intermittent CS occlusion in humans. PMID- 4036828 TI - Effects of repeated brief coronary occlusion on regional left ventricular function and dimension in dogs. AB - The cumulative effects of repeated, brief episodes of regional ischemia on myocardial function and dimension were examined in 14 open-chest dogs. The left anterior descending coronary artery was occluded for 5 minutes, followed by 10 minutes of reflow, repeated 16 times, and then 1 hour recovery. Systolic function decreased progressively in segments made repetitively ischemic and remained depressed even after 1 hour of recovery. Average systolic shortening decreased 20% from baseline after recovery from the first occlusion, 82% after the 8th, 91% after the 16th, and 104% after the 1 hour recovery (p less than 0.015, analysis of variance). End-diastolic segment length progressively increased in regions made repetitively ischemic, lengthening 4% after the first occlusion, 10% after the third occlusion, 19% after the sixteenth occlusion, and 16% after 1 hour of recovery (p less than 0.02). Nonischemic end-diastolic segment length also showed a smaller but parallel increase, while non-ischemic systolic function showed compensatory improvement. After the dogs were killed, myocardial staining with triphenyl tetrazolium chloride revealed no necrosis. Electron microscopy, performed in 5 dogs, showed scattered mitochondrial swelling in both postischemic and nonischemic regions, but no evidence of irreversible injury. The ratio of myocardial blood flow in the region made repetitively ischemic to nonischemic flow, as measured with microspheres, was 1.00 +/- 0.02 before the occlusions and 0.90 +/- 0.03 just before death (difference not significant). Thus, in the dog progressively abnormal regional systolic function and regional and global diastolic dilatation can be produced by repetitive, brief, coronary occlusions, which are not associated with histochemical or ultrastructural evidence of myocardial necrosis. PMID- 4036829 TI - Cardiac imaging with ultrasound: rightside up or upside down? PMID- 4036830 TI - Variant angina and spontaneous coronary artery dissection. PMID- 4036831 TI - Complete pulmonic valve opening during atrial contraction after right ventricular infarction. PMID- 4036832 TI - Simplified Doppler estimation of mitral valve area. PMID- 4036833 TI - Regurgitation of normal Bjork-Shiley prosthetic valves in the aortic valve position. PMID- 4036834 TI - Infusion of blood from pericardial sac into femoral vein: a technique for survival until operative closure of a cardiac perforation during balloon septostomy. PMID- 4036835 TI - Balloon occlusion angiography in infancy: methods, uses and limitations. PMID- 4036836 TI - Circulatory shock due to ascites and responsive to paracentesis. PMID- 4036837 TI - Influence of the two-stage anatomic correction of simple transposition of the great arteries on left ventricular function. AB - To evaluate the influence of the 2-stage anatomic correction of simple transposition of the great arteries on left ventricular (LV) function, pressure and angiocardiographic volume data were analyzed during resting conditions shortly before banding of the pulmonary trunk (n = 12) and before (n = 17) and after anatomic correction (n = 11), and compared with data from controls (n = 12). Age at banding and anatomic correction was between 1 and 44 months (mean 16 +/- 10) and between 13 and 47 months (mean 24 +/- 10), respectively. The interval between anatomic correction and the investigation ranged from 10 to 29 months (mean 20 +/- 7). After banding, LV ejection fraction decreased (p less than 0.01) and LV peak systolic pressure (p less than 0.01) as well as LV end-diastolic pressure (p less than 0.05) increased. After anatomic correction, these variables and LV end-systolic wall stress were not significantly different from control values. The LV end-systolic wall stress-ejection fraction relation in 7 of 11 patients after anatomic correction was within control range. The highest values were found in the youngest patients at banding and at anatomic correction. In contrast to measures of global myocardial function, such as LV ejection fraction and LV end-diastolic pressure data, the LV end-systolic stress-ejection fraction relation suggest that LV function may not be normal in some patients 20 months after anatomic correction. Young age at operation, however, appears to be advantageous in preserving LV function. Hemodynamic alterations after banding probably reflect LV adaptation to systemic pressures in a hypoxemic circulation. PMID- 4036839 TI - Anticoagulation therapy in children with mechanical prosthetic cardiac valves. AB - From 1980 through 1984, 28 children younger than 19 years (mean 7.9) underwent cardiac valve replacement with 30 mechanical prostheses. Patients were followed for a total of 471 months (mean 15.7) and received either warfarin (mean 0.16 mg/kg/day) or acetylsalicylic acid and dipyridamole (mean 6.1 and 1.9 mg/kg/day, respectively) as thromboembolism prophylaxis. The frequency and incidence of thromboembolism and hemorrhage were compared. Warfarin-treated patients were at increased risk of hemorrhage (5 of 20 [25%], or 22 per 100 patient-years, vs 0 of 10 [0%], or 0 per 100 patient-years, p less than 0.05). Three of the 5 hemorrhagic episodes were mild, and in no case was hemorrhage life-threatening. Patients who did not receive warfarin had a greater risk of thromboembolism (2 of 10 [20%], or 12 per 100 patient-years, vs 0 of 20 [0%], or 0 per 100 patient years, p less than 0.05). Both episodes of thromboembolism were life-threatening and necessitated emergency valve replacement. Although warfarin is associated with greater risk of hemorrhage than is acetylsalicylic acid and dipyridamole, warfarin is better than antiplatelet drugs in thromboembolism prophylaxis and is indicated for anticoagulation therapy in children with mechanical cardiac prostheses. PMID- 4036838 TI - Echocardiographic ventricular shape analysis in congenital heart disease with right ventricular volume or pressure overload. AB - In this 2-dimensional (2-D) echocardiographic study, a computerized Fourier analysis technique refined from one that allows quantification of changes in septal shapes in normal fetuses, newborns and infants allowed analysis of left ventricular (LV) shapes in 14 patients with right ventricular (RV) volume overload (atrial septal defects), 5 with volume and pressure overload (total anomalous pulmonary venous connection), and 10 with pressure overload (complete transposition of the great arteries [TGA] with intact ventricular septum). Diastolic shape factors in the 3 groups were significantly different from those of normal subjects (p less than 0.01). Highest diastolic values were found in patients with TGA (mean 4.59 +/- 1.28). Systolic shape factors were similar in patients with atrial septal defect and normal subjects. Significant differences existed between normal subjects and patients with total anomalous pulmonary venous connection, with the greatest differences in systolic shape factor being 5.61 for TGA vs 1.87 (p less than 0.005) for normal subjects. Shape factor correlated well with hemodynamic data for RV/LV systolic pressure ratios (r = 0.93, p less than 0.001) for normalized interventricular pressure differences (r = -0.95, p less than 0.001). The lower the normalized systolic pressure difference or the higher the RV/LV ratio, the more the septum encroached into the LV cavity. Significant but weaker correlations were noted for values during diastole. Quantitative application of Fourier shape factor analysis to LV shapes allows numerical expression of visually interpreted distortions over a wide range of geometric alterations. PMID- 4036840 TI - Extravascular lung water in children immediately after operative closure of either isolated atrial septal defect or ventricular septal defect. AB - Extravascular lung water (EVLW) was measured in 16 patients with congenital heart disease by the cold green dye, double indicator dilution technique. Five patients with optimally corrected tetralogy of Fallot served as controls, and EVLW in this group was 4.7 +/- 0.5 ml/kg (111 +/- 13 ml/m2) (mean +/- standard deviation). In 5 asymptomatic patients with atrial septal defect (ASD), normal pulmonary artery (PA) pressure and increased pulmonary blood flow, EVLW was 5.7 +/- 2.8 ml/kg (132 +/- 63 ml/m2), which was not significantly different from the value of control patients. However, in 6 patients with ventricular septal defect, PA hypertension, normal left atrial pressure and an equivalent left-to-right shunt to ASD patients, EVLW was 15.9 +/- 3.8 ml/kg (270 +/- 60 ml/m2). This was significantly different from values in both control and ASD patients (p less than 0.01). It is concluded that in the face of normal pulmonary vascular resistance, PA pressure is transmitted to the microvasculature, causing hydrostatic pulmonary edema. Other factors that may be implicated in the pathogenesis of pulmonary edema, such as increased pulmonary blood flow and relative lymphatic insufficiency in infants, cannot be excluded. PMID- 4036841 TI - Assessment of right ventricular outflow tract in children by two-dimensional echocardiography using a new subcostal view. Angiocardiographic and morphologic correlative study. AB - Evaluation of the right ventricular (RV) outflow tract in congenital heart disease is extremely important for surgical management. Therefore, the value of 2 dimensional echocardiography (2-D echo) to assess the RV outflow tract was studied using a new approach: the subcostal elongated right oblique view. Twenty normal children and 49 children with congenital heart disease, aged 1 day to 11 years, were studied. Significant pulmonary infundibular obstruction was present in 22 patients with conotruncal malformations. To obtain the subcostal elongated right oblique view from the short-axis view at the aortic valve level, the transducer was slightly rotated clockwise with an anterior angulation of about 30 degrees so that the ascending aorta was seen in its long axis, providing an image similar to that obtained by a right ventriculogram in the elongated right anterior oblique view. The deviation of infundibular septum was appreciated by measurement of the angle alpha, defined by the long axis of the infundibular septum and the plane of aortic cusps. This view could be obtained in 64 patients (92%). In correlation with angiographic or anatomic data, the subcostal elongated right oblique view permitted recognition of several types of RV outflow tract: type I--normally formed RV outflow tract; type II--disorganized RV outflow tract with obstruction (alpha less than 90 degrees); type III and IV--disorganized RV outflow tract with obstruction (alpha greater than 90 degrees). This view could visualize the crista supraventricularis in type I, but also the anatomic components of RV outflow tract that may contribute to obstruction in the other types: infundibular septum, septoparietal trabeculations and trabecula septomarginalis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4036842 TI - Echocardiographic assessment by computer-assisted analysis of diastolic left ventricular function and hypertrophy in borderline or mild systemic hypertension. AB - Systemic hypertension is a common cause of congestive heart failure. However, left ventricular (LV) systolic function remains normal for many years in patients with mild or moderate hypertension. In this study, high-quality M-mode echocardiograms were recorded in 7 patients with borderline hypertension, 14 patients with mild hypertension and 15 normal persons. Measures of systolic and diastolic LV function and the degree of LV hypertrophy were studied with the assistance of a tablet digitizer and dedicated microcomputer. Average blood pressure was 125 +/- 10/77 +/- 7 mm Hg in normal subjects, 146 +/- 18/92 +/- 2 mm Hg in patients with borderline hypertension and 150 +/- 11/102 +/- 4 in patients with mild hypertension. Indexes of systolic LV function were similar in all 3 groups. The peak rate of early relaxation of the LV posterior wall was significantly decreased in the group of patients with mild hypertension (4.7 vs 6.6 sec-1, p less than 0.01). The mitral valve closure rate was 150 +/- 32 mm/s in normal subjects, 119 +/- 35 mm/s in patients with borderline hypertension and 106 +/- 26 mm/s (p less than 0.001) in patients with mild hypertension. Mild LV hypertrophy was present in 6 of 7 patients with borderline and 13 of 14 patients with mild hypertension. The degree of hypertrophy and the level of blood pressure correlated poorly.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4036843 TI - Spectrum of acute hemodynamic effects of nifedipine in severe congestive heart failure. AB - The acute hemodynamic effects of 20 to 50 mg of orally administered nifedipine were evaluated in 31 patients with severe chronic congestive heart failure (CHF) and the results were analyzed according to the response of the cardiac index (CI). Although the group mean value of CI increased significantly after nifedipine treatment (from 2.1 +/- 0.5 to 2.4 +/- 0.8 liters/min/m2, p less than 0.001), the individual response was variable. Twenty of the patients had 15% or greater increase in CI (group A) and 11 patients had less than a 15% increase or a decrease in CI (group B). Marked differences were also noted in the effects of nifedipine on other hemodynamic variables. Stroke volume increased 29 +/- 14% in group A and decreased 11 +/- 18% in group B (p less than 0.001). Systemic vascular resistance decreased 34 +/- 11% in group A (p less than 0.001) and increased slightly, 2 +/- 28%, in group B. Left ventricular (LV) stroke work index increased 11 +/- 19% in group A (p less than 0.001) and decreased markedly in Group B (21 +/- 20%). Six group B patients had a substantial worsening (20% or more) of one or more hemodynamic measurements, including CI, stroke volume index, LV stroke work index and mean pulmonary artery wedge pressure. A comparison of control hemodynamic values at rest, LV ejection fraction, associated coronary artery disease, nifedipine dose, and concomitant diuretic therapy revealed no significant differences between the 2 groups. This study confirms, in a large group of patients with severe CHF, the variable hemodynamic effects of nifedipine therapy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4036844 TI - Mood and appetite during minimal-carbohydrate and carbohydrate-supplemented hypocaloric diets. AB - After a baseline period of free-feeding, 20 obese outpatients alternated between four 2-wk periods of minimal-carbohydrate diet (800 kcal; 58% protein and 42% fat by weight) and of a carbohydrate-supplemented diet (1,000 kcal; 42% protein, 30% fat, and 28% carbohydrate). In a comparison of psychological adjustment during the baseline and low-calorie diets, the initial 2 wk of dieting was associated with a decrease in appetite and elevation of psychological well-being, regardless of the composition of the diet. Thereafter, appetite and mood approached basal levels. Further changes in these psychological reactions to dieting did not vary with the type of diet. There was no support for the idea that a minimal carbohydrate, protein-supplemented fast decreases appetite and elevates mood more in comparison with a similar diet containing enough carbohydrate to minimize ketosis. PMID- 4036845 TI - The measurement of sodium and potassium intake. AB - Single- vs multiple-day food records were compared for estimates of intake for sodium, potassium, and calories; and the correspondence was assessed between sodium and potassium intake and 24-h urinary excretion. Fifty-five middle-aged adults, participating in a prerandomization assessment for a nutritional/behavioral intervention program on blood pressure completed a six-day food record and a 24-h urine collection. The group average for sodium, potassium, and calories obtained from one-day food records proved to be as good an estimate of the six-day average as did values from multiple day records. Similarly the one day food record proved a good estimate of the mean 24-h urinary values for sodium and potassium. If properly collected and analyzed, a one-day food record is a good estimate of a population's intake of sodium and potassium while multiple days of recording are necessary to characterize individual intake. PMID- 4036847 TI - Effect of dietary cholesterol on biliary lipids in patients with gallstones and normal subjects. AB - The purpose of this study was to determine the effect of dietary cholesterol on biliary lipids in subjects with and without gallstones. Twelve patients with asymptomatic gallstones (six men, six women) were assigned diets containing 500, 750, and 1000 mg cholesterol daily for 3-wk periods in random sequence. Seven healthy women similarly were assigned diets containing 500 and 1000 mg cholesterol daily. With increasing dietary cholesterol in patients with gallstones, biliary saturation indices and molar percents of cholesterol and phospholipids increased significantly while molar percent of biliary bile acids decreased significantly. With increasing dietary cholesterol in healthy women, the biliary saturation index and molar percent of cholesterol increased significantly; the mean saturation index exceeded unity on the diet containing 1000 mg cholesterol daily. In conclusion, augmented dietary cholesterol for brief periods increased biliary cholesterol saturation in subjects with and without gallstones. PMID- 4036846 TI - Effect of dietary cholesterol and degree of fat unsaturation on plasma lipid levels, lipoprotein composition, and fecal steroid excretion in normal young adult men. AB - Effect of four test diets differing in the ratio of polyunsaturated to saturated fats (P/S, 1.8 vs 0.28) and two cholesterol levels (1,000 vs 300 mg/day) for each level of the P/S ratio was determined on plasma lipid levels, lipoprotein compositions and concentrations, and fecal steroid excretion in a controlled diet study with 11 normal young men using a crossover design. Plasma cholesterol levels were significantly decreased by the diets high in P/S ratio regardless of the dietary cholesterol levels (14% decrease by high cholesterol and 20% in low cholesterol) while the diets low in P/S ratio increased cholesterol by an average of 24 and 22% in presence of high and low cholesterol, respectively. Lipids and apoproteins of lower-density lipoproteins were changed in accordance with those of plasma cholesterol but changes in high-density lipoprotein (HDL) appear to depend on both cholesterol content and P/S ratio. Dietary cholesterol level profoundly influenced the excretion of neutral sterols and diets high in P/S ratio significantly (p less than 0.05) increased fecal bile acid extraction. The present study demonstrated that dietary polyunsaturated fats, when a moderate amount was consumed, were effective and beneficial hypocholesterolemic nutrients without reducing HDL-cholesterol. PMID- 4036848 TI - Bioavailability of selenium to residents in a low-selenium area of China. AB - For 8 wk 5 groups of 10 men each were given 0.5 g/day DL-methionine, 150 micrograms Se/day as sodium selenite with or without methionine or 150 micrograms Se/day as selenomethionine with or without methionine. Twenty subjects received placebo as controls. Initially plasma Se rose more rapidly than RBC Se. Increases in Se levels were significantly greater with selenomethionine than with the selenite supplement. In the placebo and methionine supplemented groups neither plasma nor RBC Se varied significantly over the course of the study. Supplementation with selenium resulted in marked increases in plasma and RBC GSH Px within 2 and 4 wk, respectively. Plasma and RBC GSH-Px activity did not differ significantly between Se-supplemented groups. These studies suggest that selenomethionine-Se was more effective in raising plasma and RBC Se than was selenite-Se. Methionine supplements may increase the bioavailability of selenium in severely deficient subjects. PMID- 4036850 TI - Incidence and duration of breast-feeding in a health maintenance organization population. AB - A breast-feeding incidence and duration study in a heterogeneous population confirmed the increased incidence of breast-feeding reported among American women. Of 632 women delivering between May and August of 1980, 66% chose to breast-feed, a decision determined to be significantly related to race, age, marital status, and parity. Cesarean deliveries discouraged breast-feeding, whereas nursing immediately after delivery and keeping the infant in the room during the hospital stay encouraged breast-feeding. Of 417 women who were breast feeding, 58% had stopped by four months postpartum, a decision found to be related significantly to race, age, and receiving formula in the hospital. Formula supplementation in the hospital was associated with a shorter breast feeding period. The most rapid decline in breast-feeding occurred in the first two weeks postpartum. Because this is the period in which women are most likely to discontinue breast-feeding, it could be a productive target period for support and assistance by health professionals. PMID- 4036849 TI - A prospective trial of the effect of vitamin D supplementation on metacarpal bone loss in elderly women. AB - The effect on cortical bone loss of treating elderly women with 15,000 IU vitamin D2 weekly was evaluated by sequential radiographic morphometry of the metacarpals. One hundred nine randomly selected women aged 65-74 yr were studied for 2 yr. The women were randomly allocated to control or treated groups taking placebo or vitamin D2 capsules. Hand radiographs and blood samples were obtained at the beginning and end of the trial. Plasma 25-hydroxyvitamin D was measured by radio-competitive protein binding assay. Comparing the treated and control groups, vitamin D treatment significantly raised the plasma 25-hydroxyvitamin D levels (p less than 0.001) and reduced the rate of cortical bone loss (p less than 0.01). The placebo had no measurable effect on the plasma levels. PMID- 4036851 TI - Nutritional status of children in the health district of Cusco, Peru. AB - This study was conducted to obtain an accurate assessment of the nutritional status of the children in the Cusco, Peru Health District. It is a sample survey of anthropometric measures for 3,383 children under the age of 10 yr. The results showed a significant decline in nutritional status with age (96.88% normal range at ages 1-3 mo to only 37.43% normal at ages 12-24 mo) followed by a gradual improvement in the children above 2 yr (approximately 50% normal). The deficits at the older ages were principally due to low weights-for-age. Nutritional status was also dependent on sex, village altitude, remoteness, and population size (p less than 0.005). Of these, only sex interacted with age. The girls did significantly better at some ages and the boys better, but not significantly so, at other ages. PMID- 4036852 TI - Validity and reproducibility of a dietary history method estimating the usual food intake during one month. AB - The validity and reproducibility of a dietary history method with a time of reference of one month was assessed with 44 young adults (aged 19-32 yr). The concurrent validity of the method was assessed by means of the 24-h urine nitrogen excretion. The mean difference between N-intake and N-excretion (24-h urine N-excretion plus 2 g for extra renal nitrogen losses) was 0.0 g with 95% confidence limits of +/- 1.1 g. These limits for the mean difference between excretion and intake indicate a valid assessment of the protein intake of this group. The reproducibility was evaluated in the same group through a test-retest design. The intraclass correlation coefficients were high over a weighted average of weekdays and for an average workday with regard to the intakes of energy and selected nutrients. For the Saturday and Sunday intakes, the intraclass correlation coefficients were lower for the energy intakes and most of the nutrients (except alcohol), indicating a poorer reproducibility for weekend assessments. PMID- 4036853 TI - Why do polyunsaturated fatty acids lower serum cholesterol? AB - Replacement of saturated by polyunsaturated fatty acids in the diet may lower serum very low-density and low-density lipoprotein concentrations because the liver preferentially converts polyunsaturated fatty acids into ketone bodies instead of into very low-density lipoprotein triglycerides. Thus unlike saturated fatty acids, polyunsaturated fatty acids are transported to the tissues for oxidation without leaving a trail of lipoprotein remnants in the form of low density lipoproteins. PMID- 4036854 TI - RDA for vitamin E. PMID- 4036855 TI - Calcium intake and bone. PMID- 4036856 TI - Intramuscular myxoma--a clinicopathological study of twenty-three cases. AB - Twenty-three cases of intramuscular myxoma were analyzed clinically and histologically. The mean age of the patients was 54 years, and two-thirds were women. Clinical follow-up of 2 to 17 years' duration revealed no recurrences or metastases. Intramuscular myxoma thus appears to be a completely benign tumor. One patient simultaneously had a myxoma in the muscle of the thigh and a lesion of fibrous dysplasia in the femur. In addition, 14 of 16 patients studied with x ray had a significantly higher incidence of minor abnormalities in bones as compared with the normal population. The myxomas were characterized histologically by sparse cellularity, abundant intercellular material digestible with hyaluronidase, and lack of mitotic figures. At the ultrastructural level, the tumor cells showed characteristics of fibroblasts and myofibroblasts. Immunohistochemical analysis of intermediate filament proteins revealed vimentin- but no desmin-positivity in the tumor cells, and endothelial cell markers as well as S-100 protein were absent. This is compatible with fibroblastic myofibroblastic nature of the myxoma cells. PMID- 4036857 TI - Flow cytometric analysis of DNA in diagnostic cytology. AB - Flow cytometric analysis of nuclear DNA content and cell surface immunologic phenotyping were used in the evaluation of cytologic samples obtained from four patients. In each sample, a lymphoid cell population was present, which was difficult to evaluate by traditional cytopathologic methods. In two of the cases, the flow cytometric demonstration of monoclonal populations of lymphoid cells characterized by abnormal amounts of nuclear DNA gave support to the cytologic interpretation of malignancy. In a third sample, a lymphoid cell population that could not be cytologically distinguished from malignant lymphoma cells of small lymphoid cell type was shown to be composed of euploid, polyclonal cells. In the fourth case, the demonstration of euploidy in morphologically distinctive cell populations was helpful in interpreting the fine-needle aspirate of the thyroid gland. The authors conclude that flow cytometry can be used to great advantage in the evaluation of cytologic samples as well as in predicting biologic behavior. PMID- 4036858 TI - Plasmacytic differentiation in follicular center cell (FCC) lymphomas. AB - Although follicular centers are the sites of production of plasma cell precursors, plasmacytic differentiation in follicular center cell (FCC) lymphomas is rarely seen, presumably because of a "block" in differentiation of the large noncleaved FCC. The authors reviewed a large number of these cases to determine the frequency of plasmacytic differentiation in FCC lymphomas. In one hundred ninety-eight, consecutive FCC lymphomas with a follicular pattern from a two-year period, 17 (9%) cases were found in which there were large numbers of plasma cells. Immunoperoxidase studies of paraffin-embedded sections (PIP) for cytoplasmic immunoglobulin showed polytypic marking in ten of these and a monotypic plasma cell population in seven. In this latter group, isotypically identical marking of the plasma cell and FCC populations could be demonstrated in three cases with immunoperoxidase (where the FCCs showed cytoplasmic marking) and in one case (of one tested) with surface typing studies. In addition, three patients had serum paraproteins identical to the plasma cell cytoplasmic immunoglobulins. These findings indicate that a small minority of FCC lymphomas contain sufficient plasma cells to be a diagnostic problem, and that in some of these cases, plasma cells are a differentiated component of the FCC lymphomas. PMID- 4036859 TI - Evaluation of the Coulter Counter model S-Plus IV. AB - Evaluation of linearity, carry-over, precision, and accuracy of a Coulter Counter model S-Plus IV prototype showed that they meet the manufacturer's specifications. The instrument also was compared with an earlier model. Correlations of the lymphocyte and granulocyte values in the three-part differential count with manual eye-count and a Technicon Hemalog D90 results were very close to the correlation of eye-count to Hemalog D90 results. The percentage of mononuclear cells showed acceptable correlation to the manual eye-count when monocytes were combined with blasts, eosinophils, and basophils. The medical effectiveness of the three-part differential was determined by comparison with manual eye-counts in 1,084 samples. The false positive and false negative values were 7.38% and 7.84%, respectively. The instrument has acceptable limits of operation. When combined with analysis of histograms by trained personnel, the three-part differential count is capable of screening for abnormalities that require further analysis. PMID- 4036860 TI - Analysis of heparinization methods during hemodialysis. AB - The ideal method of heparinization should achieve therapeutic concentrations (0.2 0.5 IU/mL) in the artificial kidney and the least possible amount of heparin in the patient. Total heparinization using a bolus dose (8400 IU) followed by continuous infusion of heparin (20 IU/min), initially showed 1.4-2.4 IU/mL in the artificial kidney and the patient, but unpredictable slopes. High-dose regional heparinization (120-144 IU/min) and neutralization showed sustained heparin concentrations (0.4-0.6 IU/mL) in the artificial kidney, and less than 0.2 IU/mL in the patient. Low-dose regional heparinization (25 IU/min) initially showed 0.25-0.45 IU/mL in the artificial kidney, but unpredictable slopes in the patient. Low-dose regional heparinization (25 IU/min) and neutralization showed sustained heparin concentrations (0.15-0.35 IU/mL) in the artificial kidney and less than 0.15 IU/mL in the patient. PMID- 4036861 TI - Progressive disseminated penicilliosis caused by Penicillium marneffei. Report of eight cases and differentiation of the causative organism from Histoplasma capsulatum. AB - Eight patients with fatal penicilliosis caused by Penicillium marneffei are reported. All were natives of southern rural Guangxi, and none had a predisposing illness or evidence of altered immunity. The distinctive features of P. marneffei include proliferation of yeast-like cells within histiocytes, followed by the development of focal necrosis and, eventually, large abscesses. Outside the histiocytes, the fungi elongate, become slightly curved, and form septa. In vitro, P. marneffei produces a red pigment which diffuses into the culture medium. The differentiation between P. marneffei and Histoplasma capsulatum is described, and possible reservoirs for P. marneffei are discussed. PMID- 4036862 TI - Antimicrobial synergy testing based on antibiotic levels, minimal bactericidal concentration, and serum bactericidal activity. AB - The ratio between the concentrations of different antimicrobial agents varies widely during therapy and often bears no resemblance to the ratios assessed by in vitro methods to evaluate the effectiveness of multiple antimicrobial therapy. The authors examined an alternative method using patient serum that reflects the actual antibiotic levels achieved in the patient. Previous investigators have shown that the ratio of the concentration of free drug (drug-f) to the minimal bactericidal concentration (MBC) in broth approximates the serum bactericidal titer (SBT) when pooled normal human serum is used as the diluent. Theoretically, when two antimicrobial agents are administered, the SBT should be equivalent to (drug-f A/MBC drug A) + (drug-f B/MBC drug B). SBT and drug level determinations were performed on peak and trough serum specimens from ten patients with endocarditis or osteomyelitis who were receiving multiple antimicrobial therapy. The serum dilution synergy method predicted additive interactions twice as often as the checkerboard and kill curve, and predicted synergy less frequently than the kill curve. The checkerboard predicted antagonism four times more often than the other methods and provided equivocal results in four of ten cases. The suggested method may offer an alternative procedure to assess antimicrobial interactions, which is based on antibiotic levels actually achieved in vivo instead of the arbitrary concentrations often used in in vitro tests. PMID- 4036863 TI - Clinical utility of serum prostatic acid phosphatase measurements for detection (screening), diagnosis, and therapeutic monitoring of prostatic carcinoma; assessment of monoclonal and polyclonal enzymes and radioimmunoassays. AB - Serum prostatic acid phosphatase (PAP), measured by three different technics, was used to screen 560 men over 50 years of age for prostatic cancer. All three PAP procedures failed to detect the one subject found to have prostatic cancer on physical examination and confirmed by biopsy, and all assays had a significant number of "falsely" elevated PAP levels. Four PAP assays were assessed in 80 men undergoing prostatic biopsy/removal in whom histologic examination of prostatic tissue was made. Clinical sensitivity and specificity for detecting those patients with and without prostatic cancer ranged from 20-57% and 54-95%, respectively, with the monoclonal enzyme immunoassay being the most sensitive but the least specific, and the traditional enzyme assay being the most specific but insensitive. In men with diagnosed prostatic cancer undergoing radiation or chemotherapy, the assays were useful in distinguishing between those with active and inactive disease. The authors conclude that serum PAP assays, irrespective of the type of procedure used, has no place in screening for prostatic cancer, a minimal role in establishing a definitive diagnosis, but a useful role in monitoring therapy. PMID- 4036865 TI - Relationship between body weight and total leukocyte count in morbid obesity. AB - The authors studied the relationship between total leukocyte count and body weight in 42 morbidly obese patients (weight range, 101.5-206.8 kg). None of the patients had a recent history of infection, hematologic disorders, chronic respiratory disease, or were smoking more than 5 cigarettes/day. The range of total leukocyte count was 4.2-12.0 X 10(9) cells/L. Twelve of the 42 patients had a leukocyte count of 10 X 10(9) cells/L. There was a significant correlation between body weight (kg) and total leukocyte count (r = 0.68, P less than 0.001). Morbid obesity should be considered as one of the causes of physiologic leukocytosis. PMID- 4036864 TI - Statistical analysis of relationship between iron accumulation and hepatitis B surface antigen. AB - Statistical analysis was carried out to determine the relationships of iron deposition among hepatocytes, Kupffer cells, bile duct epithelial cells, portal tracts, and spleens using 68 autopsy cases obtained from Kenya, which included cases of Bantu siderosis. Of 68 cases, 33 (49%) showed siderosis. Cirrhosis was observed in 19 cases, of which 10 (53%) showed siderosis. However, there was no correlation between iron deposition and cirrhosis (Pearson chi 2 = 0.6734). The finding suggests that iron accumulation does not lead to cellular injury. On the other hand, there was a strong association between iron deposition in the livers and that in the spleens. There was also a strong correlation between the presence of hepatitis B surface antigen and iron deposition in the Kupffer cells and in the spleens. Therefore, it is suggested that the hepatitis B virus infection affects the iron metabolism of the reticuloendothelial system. PMID- 4036866 TI - A comparison of differential white blood cell counts using manual technic and the Coulter S-Plus IV. AB - The results of 100-cell and 500-cell manual differential white blood cell counts were compared with those obtained using a Coulter S-Plus IV electronic particle counter. Significant (P less than 0.001) correlations were observed between the manual and instrument-derived data for percentages of granulocytes and lymphocytes. PMID- 4036867 TI - Heparin monitoring by activated partial thromboplastin time. Comparison of ex vivo measurement and in vitro standardization. AB - Twenty patients were studied prospectively during heparin therapy. Three activated partial thromboplastin time (APTT) reagents were used to compare APTT values with plasma heparin levels during induction of heparin and transition of heparin to coumadin. A heparin in vitro dose APTT response curve and a heparin ex vivo curve were established. The in vitro sensitivity curves using different reagents were varied at therapeutic heparin levels. In contrast, the APTT reagents did not differ ex vivo. The in vitro curves demonstrated poor performance. Sixty percent of the patients did not adequately compare by APTT estimation of plasma heparin levels. An APTT ratio (1.5 to 2.5) using the patient's baseline APTT as the denominator demonstrated better representation of heparin levels. The in vitro APTT curves are inappropriate for heparin monitoring. PMID- 4036868 TI - The detection of penicillin-resistant pneumococci. The compliance of hospital laboratories with recommended methods. AB - Isolations of pneumococci with diminished susceptibility to penicillin have been reported with increasing frequency in recent years. The first reported isolations of such organisms in Tennessee occurred in December 1982, and prompted a survey of acute-care hospitals to determine the methods being used to test pneumococcal isolates for penicillin susceptibility. All 77 acute-care hospitals in Tennessee with 100 or more beds were surveyed. Eighteen (23%) did not test the penicillin susceptibility of any pneumococcal isolates obtained from blood or cerebrospinal fluid. Thirty-eight hospitals (49%) tested some or all such isolates, but did not perform the tests in accord with established standards; 21 (27%) properly tested all such isolates. There was no correlation between the proper testing of pneumococcal isolates for penicillin susceptibility and the mode of governance, numbers of beds, or medical school affiliations of the respondent hospitals. It is recommended that appropriate pneumococcal isolates be tested for penicillin susceptibility. Such testing is most reliably performed by the disk diffusion method, using a 1-microgram oxacillin disk. PMID- 4036869 TI - Colorimetric measurement of plasma lactate. AB - A rapid and simple enzymatic method for plasma lactate is proposed using stable reagents to produce the formazan color. This method agrees well with a reference kit method, r = 0.955 and the regression equation is y = 0.99x + 0.09. The over all recovery averages 100%, with a precision ranging from 0.6 to 3.3%. No interferences have been shown with the formazan reaction. The proposed method is inexpensive, ideal for batch analyses, and is an attractive method for the busy clinical laboratory. PMID- 4036870 TI - Immune hemolytic anemia associated with probenecid. AB - Upon hospital admission a patient was found to have severe anemia and a strongly positive direct antiglobulin test (DAT). The patient was taking probenecid periodically for gout. An antibody was detected in the patient's serum that only reacted with red blood cells (RBCs) when probenecid was added. Eluates from the patient's RBCs, with and without the presence of drug, were nonreactive. Upon the discontinuation of probenecid, the patient's hemoglobin level improved steadily. We believe this to be the first reported case of immune hemolytic anemia associated with probenecid. PMID- 4036872 TI - To replicate or not to replicate, that was the question. PMID- 4036871 TI - Spuriously high platelet counts. PMID- 4036873 TI - Specificity of Leu-M1 antibody for Reed-Sternberg cells. PMID- 4036874 TI - Endotoxinemia and neonatal necrotizing enterocolitis. PMID- 4036875 TI - The bone marrow in AIDS. A histologic, hematologic, and microbiologic study. AB - During one year, 55 bone marrow biopsies from 49 patients with CDC-defined acquired immune deficiency syndrome (AIDS) were studied. Eighty-three percent were normocellular or hypercellular; 17% were hypocellular. Marrow plasma cells were increased in 83% of patients, most showing polyclonal hypergammaglobulinemia. Forty percent of patients showed peripheral neutropenia, 29% thrombocytopenia, and 79% lymphopenia with markedly reduced T4+ lymphocytes. Eighty-five percent of patients were anemic, with iron studies showing a pattern consistent with the anemia of chronic disease. Mycobacterium avium-intracellulare (MAI) grew from ten (20%) biopsies, four with granuloma and six without granuloma (five of these six also showed marrow hypocellularity). Small poorly formed granuloma (70-150 micron) were seen in eight (16%) patients (four AFB-culture positive, 4 negative). Three of four granuloma-positive, culture-negative cases eventually grew MAI from autopsy material. Five (10%) patients had lymphoplasmacytic aggregates; later, one developed lymphoma, another, markedly atypical lymphoid hyperplasia. Two additional patients showed marrow B-cell lymphomas. Of these findings, only marrow MAI meets the CDC definition of AIDS. However, in this series, small ill-defined granulomas, lymphoplasmacytic aggregates, and B-cell lymphomas also were found. The authors conclude that these latter findings, when seen in high-risk patients, particularly those with lymphopenia, anemia, and/or hypergammaglobulinemia, also strongly suggest the diagnosis of AIDS. PMID- 4036877 TI - Cystic dysplastic kidneys associated with Dandy-Walker malformation and congenital hepatic fibrosis. Report of two cases. AB - The combined abnormalities of Dandy-Walker malformation, congenital hepatic fibrosis, and generalized cystic dysplastic kidneys were found in two sanguineously unrelated premature babies. This type of cerebrohepatorenal malformation is certainly unique and is generally diagnosed based on the characteristic renal lesion. Remarkably, similar renal lesions have been found in Meckel's syndrome, Goldston's syndrome, and Miranda's syndrome. The present cases can be distinguished from Meckel's syndrome on the basis of the presence of Dandy Walker malformation and the absence of polydactyly and occipital meningoencephalocele. Although the authors' cases resemble the latter two syndromes in terms of the presence of Dandy-Walker malformation, it is tentatively considered that the distinct triads found in the present cases could represent a new variant of a multiple malformation syndrome with generalized cystic dysplastic kidneys. The etiology of these cases remains unclear, but a genetic factor, which has been suggested as for other syndromes, might be involved. PMID- 4036876 TI - The significance of protein C antigen in acute and chronic liver biliary disease. AB - Protein C, a naturally occurring inhibitor of blood coagulation, was measured immunologically in 160 patients with acute and chronic liver and biliary disease. In 31 patients with acute viral hepatitis serially studied from admission to discharge from hospital, protein C antigen (PC:Ag) was low on admission in a high proportion of cases (61%) but became normal in 90% of them after two weeks at a time when the prothrombin time was still prolonged in 46% of the cases. PC:Ag was also low in 25 cirrhotic patients and in 20 patients with chronic active hepatitis. In chronic hepatitis and cirrhosis, PC:Ag levels significantly correlated with indexes of liver synthetic function. In primary biliary cirrhosis (n:40), PC:Ag was low in patients with advanced disease (stages III-IV) but high in the early phases, when cholestasis was not yet accompanied by impaired protein synthesis. PC:Ag was also very high in 20 patients with large bile duct obstruction and highly correlated with indexes of cholestasis. The authors' findings indicate that PC:Ag is reduced in liver disease proportionally to the impairment of the liver synthetic function and that its normalization after acute hepatitis might represent an early marker of recovery of this function. PMID- 4036878 TI - Evaluation of the Coulter three-part differential screen. AB - An evaluation of the Coulter Electronics, Inc. (Hialeah, FL) three-part differential screen (3PD) was undertaken to determine the performance characteristics of this system. The 3PD measures white blood cell (WBC) volumes and, by automatic analysis of the resultant WBC histogram, produces a determination of the number and percent of lymphocytes, mononuclear cells, and granulocytes. A group of 984 random patient blood samples was tested. The overall review rate (samples requiring some further analysis or review) was 42%. The main source of false negatives on the 3PD was eosinophilia: 5 out of 22 instances of eosinophilia greater than 750/microL were not flagged. The precision of the three parameters, measured as percent coefficient of variation, was 3.3% for lymphocytes, 14.2% for mononuclear cells, 3.1% for granulocytes, and 2.4% for the total WBC. The stability of blood samples was acceptable for up to eight hours at room temperature (less at 4 degrees C). PMID- 4036879 TI - Discrepant fibrinogen values during thrombolytic therapy. Comparison of aca and Data-Fi results using immunofixation. Electrophoresis as a reference. AB - The authors compared aca and Data-Fi fibrinogen values and used a combination of plasma protein electrophoresis and immunofixation with anti-fibrinogen anti-serum to observe changes in fibrinogen from four patients receiving streptokinase (STK) therapy. For three patients, aca and Data-Fi values pre-STK and greater than or equal to 24 hours post-STK correlated well (r = 0.96, slope = 0.92, y-intercept = 2.3; n = 13 pairs); aca and Data-Fi values during STK therapy correlated poorly (r = 0.67, slope = 0.36, y-intercept = 4.1; n = 20 pairs), with aca values up to sixfold higher than Data-Fi. Protein electrophoresis and immunofixation showed loss of the discrete fibrinogen band during STK therapy; instead there was a diffuse electrophoretic zone of anti-fibrinogen reactive material having a slightly different mobility than intact fibrinogen; aca fibrinogen values were inconsistent with fibrinogen band absence. The remaining patient showed no change in the fibrinogen band. Clinically he showed no response to STK therapy. In nonresistant patients, STK results in the degradation of fibrinogen into a mixture of products (FDP), all sharing antigenic determinants with fibrinogen and at least one being still clottable. Our results exemplify loss of intact fibrinogen with persisting anti-fibrinogen reactive FDP during STK therapy. Discrepancies in aca versus Data-Fi results may be due to ways in which FDP interact with different methods--fibrometer versus turbidimetric. PMID- 4036880 TI - Use of commercially prepared control sera as quality control materials for spectrophotometric bilirubin determinations in amniotic fluid. AB - The visible absorption spectra of dilutions of commercially prepared chemistry control sera closely mimic those of jaundiced amniotic fluids in cases of fetal rhesus isoimmunization. The authors have assessed the use of these materials for the quality control of net absorbance measurements at 450 nm on amniotic fluids. The authors conclude that they are excellent quality control materials because of their ready availability, low cost, long-term stability, wide range of bilirubin concentrations, and their close resemblance to jaundiced amniotic fluids with respect to light absorption and scattering, sensitivity to light, and pigment extractability into chloroform. Their spectra also contain a maximum at 410 nm, so these materials can also be used as controls for net absorbance measurements at 410 nm, a determination that indicates the extent of heme or meconium pigment interference with net absorbance measurements at 450 nm. These materials both supplement and complement the requisite spectrophotometric performance checks of wavelength calibration and photometric accuracy. PMID- 4036881 TI - The measurement of fractionated bilirubin by Ektachem film slides. Method validation and comparison of conjugated bilirubin measurements with direct bilirubin in obstructive and hepatocellular jaundice. AB - The authors evaluated the Kodak Ektachem Slides for total, "direct," conjugated, unconjugated, and albumin-bound ("delta") bilirubin. For various concentrations of control material, the precision (CV) within- and between-day ranged from 1.7 to 2.4% (2.8-6.6%) for total bilirubin, 0.8-4.2% (1.6-11.5%) for unconjugated bilirubin, and 1.6-9.5% (2.6-20.7%) for conjugated bilirubin. The Ektachem total and "direct" bilirubin assays demonstrated excellent correlation with the Jendrassik and Grof procedure; a 30% difference was observed, however, between absolute numbers with the two direct bilirubin methods. We found the measurement of true conjugated bilirubin by the Kodak Method to be superior to the measurement of "direct" bilirubin in following the response to treatment of various hepatic disorders manifested by extrahepatic and intrahepatic biliary obstruction. PMID- 4036882 TI - Penile glycogenated epithelial cells as an indicator of recent vaginal intercourse. AB - Occasionally, suspected male rape assailants are examined, in part to recover evidence of recent sexual intercourse. Glycogenated squamous epithelial cells are felt to be specific for the vagina, and if recovered from the penis, they are indicative of penile vaginal penetration. From the 45 periodic acid-Schiff (PAS) stained postcoital penile smears examined, 36 (81%) contained PAS-positive cells. Precoital penile smears were all negative. Both precoital and postcoital urethral meatus smears contained many PAS-positive cells. The authors conclude that recovery of PAS-positive cells from the penile shaft is strong presumptive, but not definitive, evidence of recent vaginal intercourse. PMID- 4036883 TI - The measurement of fibrinogen by the DuPont aca and Dade methods in patients receiving streptokinase infusions. AB - To assess the discrepancies noted in fibrinogen measurement by the DuPont aca and Dade methods, nine patients receiving streptokinase (SK) by either the intracoronary (IC) (240,000 IU/60 minutes) (two patients) or intravenous (IV) (1,500,000 IU/45 minutes) routes (seven patients) for acute myocardial infarctions were studied over 48-72 hours. All nine patients showed a rapid and profound fall in fibrinogen to unrecordable levels (30 mg/dL) by the Dade method. Three patients showed a similar response to unrecordable levels (less than 50 mg/dL) with the DuPont aca method. Six others had less of a decrease with the DuPont aca method compared with the Dade method. One patient showed a gradual fall by the DuPont aca method to reach 60% of the preinfusion level at 30 hours, whereas the minimal value by the Dade method, 81% of the preinfusion level, was reached within 12 hours. There was no difference in fibrinogen levels by the Dade method after absorption of heparin-like activity with triethylamino ethyl (TEAE) cellulose. Fibrinogen degradation products (FDPs) were elevated in all patients post-SK infusion. These studies show that fibrinogen estimation by DuPont aca and Dade methods may yield discrepant results in approximately 66% of patients treated with SK. This may have some clinical relevance to clinicians who rely on the DuPont aca fibrinogen estimation to monitor effectiveness of SK therapy. PMID- 4036884 TI - Adenomatous tumor of the middle ear. An ultrastructural and immunocytochemical study. AB - An adenomatous tumor of the middle ear was examined by light microscopy, ultrastructural and immunocytochemical technics. It demonstrated the typical histologic growth pattern and featured ultrastructural evidence of glandular differentiation with two distinct types of secretory granules, apically oriented mucus granules and basally located uniformly condensed neurosecretory granules. In support of its neuroendocrine differentiation was the detection of neuron specific enolase and positive reaction with monoclonal antibody to chromogranin. These findings are compared with previously reported cases and with middle ear mucosa. It is suggested that this bidirectional differentiation is analogous to that seen in other endodermally derived neuroendocrine tumors. PMID- 4036885 TI - Osseous pseudotumor. The sole manifestation of sinus histiocytosis with massive lymphadenopathy. AB - Sinus histiocytosis with massive lymphadenopathy may involve extra-nodal tissue sites. Skeletal involvement is uncommon and has always been associated with disease in other nonosseous locations. The present case is the first to document sinus histiocytosis with massive lymphadenopathy arising primarily within bone and unaccompanied by disease elsewhere. PMID- 4036886 TI - Nutrient intakes of American infants and children fed cow's milk or infant formula. AB - Between April 1984 and August 1984, a national survey, the Ross Laboratories Infant Nutrition Survey, was undertaken to assess patterns of food consumption of American infants ranging in age from 6.5 months to 13.4 months. Nutrient intakes of 865 infants were evaluated according to different foods (milk and milk products, non-iron-fortified formula, iron-fortified formula, infant cereal, commercial baby foods, and home-prepared table foods). Results indicated that most American infants consumed nutrients in appropriate amounts. However, a large proportion of infants who were fed a diet that included cow's milk received amounts of sodium, potassium, and chloride that exceeded the recommended safe and adequate ranges. The median intake of iron of infants fed either cow's milk or a non-iron-fortified formula was below the recommended dietary allowance; a low percentage of these infants received medicinal iron supplementation. The results also indicated that the median estimated renal solute load of the diet of infants fed cow's milk was approximately twice the amount of that of infants fed formula. These data may be useful in the development of nutritional programs for older infants. PMID- 4036887 TI - Arterialized capillary blood gases and acid-base studies in normal individuals from 29 days to 24 years of age. AB - Studies of arterialized capillary blood gases and acid-base values were performed on 712 normal persons who were between the ages of 29 days and 24 years. The results were divided for clinical use into six groups by age; linear regression lines were constructed for better understanding of the development of blood gas levels and the acid-base balance. The blood pH essentially remained unchanged throughout the study period. The oxygen and carbon dioxide pressures, base excess of extracellular fluid, and buffer base and bicarbonate levels are lower in infants than in children and adults; adult values are reached at approximately 7 to 12 years of age. The probable explanation for the lower values in infants is discussed. The effects of crying on the composition of blood gases are mentioned. PMID- 4036888 TI - The GPEP Report--a time for change in medical education. PMID- 4036889 TI - Congenital hypothyroidism. The effect of stopping treatment at 3 years of age. AB - Fifty-six children with congenital hypothyroidism diagnosed by neonatal screening were reviewed at 3 years of age or older. The presence or absence of the thyroid gland was determined by radionuclide scanning prior to treatment in the newborn period. Thyroxine therapy was discontinued in those children who did not have anatomic defects or a secondary rise in their thyrotropin (thyroid-stimulating hormone [TSH]) level once it was suppressed by thyroid hormones. Sixteen of 17 children developed a low thyroxine and an elevated TSH level within three to six weeks. One child was not receiving thyroxine for nine months and was clinically and biochemically euthyroid. We conclude that (1) newborn thyroid scans are useful to determine the cause of hypothyroidism, (2) a secondary rise in the TSH level indicates permanent hypothyroidism, (3) only about one third of infants whose condition is diagnosed by newborn screening will qualify for a trial off therapy at 3 years of age, (4) only 1% to 2% of infants whose condition is diagnosed by newborn screening have transient hypothyroidism, and (5) a three week period of hormone withdrawal after the age of 3 years seems adequate and safe to confirm permanent hypothyroidism. PMID- 4036890 TI - Antecedents of cerebral palsy. I. Univariate analysis of risks. AB - A large prospective study investigated prenatal and perinatal antecedents of chronic motor dysfunction (cerebral palsy [CP]), evaluating approximately 400 characteristics of the mothers, pregnancies, or deliveries. In addition to confirming some, but not all, of the classic risk factors for CP, this study observed relatively large increases in the CP rate in association with maternal mental retardation, seizure disorders, hyperthyroidism, or with the administration of thyroid hormone and estrogen in pregnancy. Some risk factors were predictive of CP only insofar as they were associated with low birth weight or low Apgar scores. Among factors not significantly related to CP rate were maternal age, parity, socioeconomic status, smoking history, maternal diabetes, first trimester vaginal bleeding, kidney or bladder infection, moderate hypertension, long cord, use of anesthetic agents, or use of oxytoxics for initiation or augmentation of labor. Duration of labor, whether precipitate or prolonged, was not a risk factor for CP. PMID- 4036891 TI - Radiological case of the month. Stridor due to double-aortic-arch anomaly. PMID- 4036892 TI - Tissue pH monitoring by a disposable sensor in critically ill neonates. AB - Using a new disposable polymer sensor, tissue pH was continuously monitored successfully in 33 critically ill neonates. Tissue pH correlated well with the arterial pH at wide pH ranges [n = 476; r = .84; y = 0.46 + (0.94)x]. Tissue pH changes accurately reflected the arterial pH during both respiratory and metabolic acidosis and alkalosis. During severe metabolic acidosis (arterial pH less than 7.10) tissue pH was lower than arterial pH. No complications were encountered during or after monitoring. Compared with earlier studies using a glass electrode, this electrode reflects a marked technologic improvement because of its ease of application, longevity of use, disposability, and decreased risk of complications in small preterm infants. Unlike transcutaneous oxygen and carbon dioxide sensors, this device is invasive but is not heated and does not require frequent site changes. PMID- 4036893 TI - Penicillin-intermediate pneumococci in a children's hospital. AB - During the three-year period from 1981 to 1984, all clinical isolates of Streptococcus pneumoniae were screened for resistance to penicillin in the clinical bacteriology laboratory at The Children's Hospital of Alabama, Birmingham. Twenty-eight of 828 isolates were presumed resistant by disk diffusion testing with 1-microgram oxacillin disks (zone diameter, less than 20 mm). Seventeen of the 28 (61%) were found to be intermediately sensitive to penicillin by a conventional agar dilution method. Penicillin-intermediate strains had a minimal inhibitory concentration of 0.125 to 0.5 mg/L; no penicillin-resistant (minimal inhibitory concentration, greater than 1 mg/L) strains were encountered. The prevalence of penicillin-intermediate strains was thus 17 of 828 isolates, or 2.1%. These strains were also examined for susceptibility to ampicillin, vancomycin, cefotaxime, and chloramphenicol. We present the clinical features of 17 patients with disease due to penicillin intermediate pneumococci. PMID- 4036894 TI - Prognostic variables in nearly drowned, comatose children. AB - Prognostic variables were evaluated in 51 nearly drowned, comatose children, and they included values for age, estimated submersion time, initial arterial pH and core temperature, mean intracranial pressure (ICP), and mean cerebral perfusion pressure (CPP); the latter two values were obtained during the first 24 hours. There were 33 survivors (19 with intact neurologic survival and 14 with brain damage) and 18 deaths. Estimated submersion time and mean ICP and mean CPP determined survival but could not predict the neurologic outcome (intact survival or brain damage). Age, arterial pH, and core temperature were not useful variables in predicting outcome. This study discourages the use of these unreliable variables in predicting survival in nearly drowned, comatose victims and, in addition, cautions against the use of mean ICP, mean CPP, and submersion time as predictors of neurologic outcome. Since mean ICP and mean CPP measurements are reliable in predicting survival but not neurologic outcome, major efforts should be undertaken to explore neurophysiologic and metabolic prognostic factors that may either discourage or mandate early institution of aggressive cerebral resuscitative measures in nearly drowned victims. PMID- 4036895 TI - Renal adaptation to extrauterine life in patients with respiratory distress syndrome. AB - A spontaneous diuresis that precedes the improvement of pulmonary function has been described in patients with respiratory distress syndrome (RDS). The developmental changes in renal physiology responsible for this spontaneous diuresis are not completely understood. To describe the mechanisms responsible for the spontaneous diuresis, serial renal function studies were performed during the first five days of life in nine premature neonates with RDS. Diuresis was defined as a urine output that was at least 80% of fluid intake; prediuretic, diuretic, and postdiuretic periods were observed in all study infants. Oxygenation did not improve until the postdiuretic period. Renal function studies disclosed a significant increase in free water clearance during the diuresis with the production of dilute urine and a reciprocal rise in serum sodium concentration and plasma osmolality. The glomerular filtration rate increased at the onset of diuresis and remained elevated after the diuresis ended; however, the proportion of filtrate excreted was significantly elevated during the diuresis compared with prediuretic and postdiuretic values. These data suggest that the diuresis in patients with RDS is a water diuresis secondary to an endogenous water load. PMID- 4036896 TI - On-line documentation of measles-mumps-rubella vaccine inoculation. PMID- 4036898 TI - Nuchal cord as a cause of neonatal anemia. PMID- 4036897 TI - Complications involving augmentin. PMID- 4036899 TI - The pediatrician's obligation in smoking education. PMID- 4036901 TI - The adolescent and young adult with heart disease. PMID- 4036900 TI - Primary care. Does it belong in pediatrics? PMID- 4036902 TI - Earlier maturation of pregnant black and white adolescents. AB - A survey was made of the menarcheal age and anthropometry of 1,844 lower income, nulliparous female patients receiving prenatal care. No differences were observed between black and white patients in height and maximum pregnant weight. A significantly earlier mean menarcheal age was observed in adolescents (12 to 16 years) compared with adults (17 to 31 years). Younger adolescents (12 to 14 years) of both races were taller and heavier (prepregnancy) than National Center for Health Statistics standards and had a significantly greater weight-for height. Menarcheal age and body habitus were consistent with other reports that younger pregnant adolescents tend to be earlier maturers than older pregnant adolescents and adults. Compared with their age-group cohorts (13 to 31 years) in the two-decades-old Collaborative Perinatal Study of the National Institute of Neurological Communicative Disorders and Stroke, these female patients were larger and had greater pregnancy weight gains. These anthropometric findings may reflect the two decades of improvements in social assistance and prenatal care for lower income women. PMID- 4036903 TI - QTc and R-R intervals in victims of the sudden infant death syndrome. AB - Electrocardiograms obtained during sleep within the first and/or fourth week postnatally were available on eight infants who subsequently died of the sudden infant death syndrome (SIDS). The corrected QT (QTc) and R-R intervals were compared with controls for the purpose of evaluating their relevance for SIDS. The QTc interval in controls increased with age and tended to be longer during sleep without rapid eye movements. The R-R interval decreased with age. None of the SIDS victims was found to have a prolonged QTc interval. However, the R-R interval during rapid eye movement epochs was significantly shorter in future SIDS victims compared with controls. These data were interpreted as being inconsistent with the congenital variants of the long-QT hypothesis but compatible with the growing conviction that infants who die of SIDS have a chronic underlying abnormality that has subtle manifestations within the immediate postnatal period. PMID- 4036904 TI - Physician-patient communication. Understanding congenital heart disease. AB - Mothers' descriptions of their childrens' congenital heart disease were compared with cardiologists' diagnoses. Maternal understanding was examined with respect to 21 factors using bivariate contingency tables and multiple regression analyses. Of 285 mothers, 36% demonstrated poor comprehension. Maternal understanding was associated with sociodemographic variables but not with factors related to stress. All variables taken in concert that were predictive of understanding explained less than 13% of the variability in maternal knowledge. Distorted perceptions of congenital heart disease may cause unnecessary anxieties, inappropriate restrictions, and impairment of the child's self perception. The bizarre nature of some of the mothers' incorrect descriptions and the accuracy of responses of mothers in biologic and health care occupations suggest that fundamental ignorance of the cardiovascular system may be of such importance as to minimize the impact of other variables. PMID- 4036905 TI - Effectiveness of pediatric and adult CPR. PMID- 4036906 TI - Measles reimmunization. PMID- 4036907 TI - Hearing loss and persistent pulmonary hypertension. PMID- 4036908 TI - Palatal groove formation and oral endotracheal intubation. PMID- 4036909 TI - Elevated transaminase levels and neuromuscular pathology. PMID- 4036911 TI - The rise of the academic clinician. PMID- 4036910 TI - Juvenile metabolic gout. PMID- 4036912 TI - Hepatitis B virus and Schonlein-Henoch purpura. PMID- 4036913 TI - Growth quotients, Z scores, and failure to thrive. PMID- 4036914 TI - Unfortunately, more on duplicate publication. PMID- 4036915 TI - Aspirin in juvenile rheumatoid arthritis. PMID- 4036916 TI - Where you stand depends on where you sit. The need for improved skills in evaluating children and families. PMID- 4036917 TI - Reye syndrome and juvenile rheumatoid arthritis in Michigan. AB - Reye syndrome (RS) is believed to occur infrequently among children receiving long-term aspirin therapy. We reviewed all cases of RS reported to the Michigan Department of Public Health during 1982 and 1983. Three of the 36 patients were receiving aspirin for the treatment of juvenile rheumatoid arthritis. All three patients had clinical courses characteristic of RS and two had supportive histologic findings on liver biopsy. The incidence of RS among children with juvenile rheumatoid arthritis is significantly greater than the incidence of RS among children who do not have juvenile rheumatoid arthritis. These findings support previous studies that showed that the use of aspirin during the antecedent illness may be a risk factor for the development of RS. Physicians should be aware of the potential for the development of RS among children who are receiving long-term aspirin therapy for the treatment of systemic inflammatory illnesses. PMID- 4036918 TI - The mistaken diagnosis of child abuse. A form of medical abuse? AB - The suspected diagnosis of child abuse may prove to be unfounded. Reports in the literature have focused on unusual diseases and folk medicine practices that may mimic abuse. We report ten cases where allegations of abuse were lodged against parents because the treating physicians in the emergency room mistook life threatening illness or postmortem artifacts for inflicted injury. In all cases the families were from the inner city, and with two exceptions the involved institutions were small hospitals without pediatric personnel present in the emergency department. Although the histories related by the parents were in all cases truthful and consistent with the results of physical examinations of the child, the involved physicians failed to make a correct diagnosis. Not only a lack of experience with severe childhood illness and death but also an attitude of suspicion and/or hostility probably contributed to these misdiagnoses. PMID- 4036919 TI - Should child abuse and neglect be considered when a child dies unexpectedly? AB - Deaths during two years at a pediatric teaching hospital were studied to develop guidelines for clinicians who must decide when to explore the possibility of child abuse or neglect when a child dies unexpectedly. Unexpected deaths were defined as deaths occurring before arrival at the hospital or within ten days of hospitalization in children past the first month of life and unrelated to any previously known congenital anomaly or medical condition. There were 43 such deaths during two years. The majority (27) were due to natural causes. However, nine deaths were related to suspected child abuse or neglect (SCAN) and in three of those cases evidence of injury was found only at autopsy. The SCAN cases were more often mistaken for medical illness than for uninflicted injury, indicating that autopsy and postmortem skeletal survey are warranted whenever a child dies unexpectedly. The two factors "dead on arrival" and "1 year of age or less" had a positive predictive value for SCAN of 89% and a negative predictive value of 94%. The two factors identify a high-risk group requiring at least hospital-based investigation into the possibility of abuse or neglect. Reporting for SCAN is warranted when unsuspected trauma is found post mortem, there is direct physical or social evidence of child abuse or neglect, or the child is in the high-risk group and hospital-based investigation falls to eliminate the possibility that maltreatment contributed to the child's death. PMID- 4036920 TI - Major impediments to measles elimination. The modern epidemiology of an ancient disease. AB - Great success has been achieved in controlling measles in the United States with a greater than 99% reduction in incidence rate from the prevaccine era. However, since 1981, the incidence rate of measles in the United States has been relatively stable at approximately 1,500 to 3,000 reported cases annually. We reviewed available information to determine the remaining impediments to elimination of measles. The potential impediments can be divided into two categories: (1) implementation of the current strategy and (2) whether the current strategy needs modification. The major reason for the failure to achieve elimination appears to be the fact that some persons for whom vaccine is indicated have not been vaccinated. While vaccine failures and importations play a role in transmission, sustained transmission in a totally vaccinated community has not been demonstrated. All chains of transmission have involved some unvaccinated persons. Measles elimination will require complete implementation of current strategies and careful monitoring of epidemiologic trends to determine whether future modifications in strategy are needed. PMID- 4036921 TI - Bacterial and viral pathogens causing fever in infants less than 3 months old. AB - We studied 182 sick, febrile (temperature greater than 38 degrees C) infants less than 3 months of age, who presented at our Tripler Army Medical Center, Honolulu, during a one-year period, to determine the relative causes of fever in this age group. Blood, cerebrospinal fluid, urine, nasopharyngeal secretions, and stool specimens were cultured for bacterial and viral pathogens. Paired acute and convalescent sera were collected to serologically confirm infection in infants from whom viral isolations were obtained only from the nasopharynx or stool. A viral pathogen was isolated in 75 infants (41%) and a bacterial pathogen was isolated in 27 infants (15%). Nonpolio enteroviruses were the most common pathogens demonstrated. They were isolated from 64 infants (35%), and 40 (62%) of these infants had aseptic meningitis, the most frequently made diagnosis. Urinary tract infection was the most common bacterial infection observed. It occurred in 20 infants (11%) and was most often seen without associated pyuria in uncircumcised male infants. Salmonellosis, the second most common bacterial infection, was observed in six infants (3%), and two of these did not have diarrhea or other gastrointestinal tract symptoms. No infant had septicemia and only one infant had bacterial (group B streptococcal) meningitis. PMID- 4036922 TI - Acalculous cholecystitis in the neonate. AB - Pediatric acalculous cholecystitis is a well-described though uncommon affliction. However, during the neonatal period nonlithogenic biliary disease is extremely unusual and only isolated reports of this problem exist. Nine previously reported cases are reviewed, and an additional case of a 6-day-old female neonate with a right-upper-quadrant mass is presented in detail. Inflammatory gallbladder disease in the neonate is often associated with concurrent systemic illness. An abdominal mass is palpable in almost all cases. Diagnosis may be confirmed in these patients by radionuclide scanning and ultrasonography. The treatment is cholecystectomy. PMID- 4036923 TI - A method for the teaching of interviewing skills. PMID- 4036924 TI - Transmission of neonatal listeriosis in a delivery room. AB - Two cases of neonatal listeriosis occurred in a hospital within a two-week period. Both infants were infected with the same organism, Listeria monocytogenes, type 1a, bacteriophage type 6 (lysotype 1652). Both infants were born in the same delivery room, 17 hours apart. The index patient became septic shortly after birth and died after 48 hours despite antibiotic therapy. The mother of the index patient was febrile and had chorioamnionitis. The second infant became ill with meningitis at 13 days of age. Neither infants nor mothers were attended by the same medical or nursing staff nor were they in the same labor or postpartum areas or nurseries. However, both infants were resuscitated in the same delivery room after birth by means of laryngoscope, suction catheter, and emergency resuscitation (Ambu) bag. Although it was hospital policy to clean and sterilize resuscitation equipment after use, the equipment had only been wiped with alcohol between patients in this instance, since sterile replacement equipment was not available during the early-morning hours when the index birth occurred. Therefore, we believe the contaminated resuscitation equipment was the source of infection in the second infant. This episode emphasizes the importance of appropriate disinfection of respiratory resuscitation equipment to prevent nosocomial infection due to L monocytogenes, an unusual but important pathogen in neonates. PMID- 4036925 TI - Effectiveness of mumps vaccine in a school outbreak. AB - An outbreak of mumps in a middle school (grades 6 through 8) in Ohio during 1981 was investigated to determine the effectiveness of mumps vaccine. Of the 481 middle school students on whom questionnaires were completed, 62 (12.4%) exhibited clinical mumps. The overall vaccine efficacy was 81.2% when children with a history of mumps disease are excluded from the analysis. Using a logistic regression model with the presence or absence of clinical mumps as the dependent variable, three factors were found to be significant: mumps vaccine, a history of mumps disease, and sex. Factors that did not significantly affect the rate of disease among vaccinated pupils included whether the mumps vaccine was administered singly or in combination with rubella and/or measles vaccine, age at vaccination, year of vaccination, and month of vaccination. PMID- 4036926 TI - Postnatal changes in calcium-regulating hormones in very-low-birth-weight infants. Effect of early neonatal hypocalcemia and intravenous calcium infusion on serum parathyroid hormone and calcitonin homeostasis. AB - In very-low-birth-weight (VLBW) infants, we studied the hypotheses that in early neonatal hypocalcemia the serum parathyroid hormone (PTH) concentration would rise; the serum calcitonin (CT) concentration would decline; and, in response to intravenous (IV) calcium (Ca) infusion, the serum PTH concentration would be lowered; and the serum CT concentration would rise. Fifteen infants appropriate for gestational age (age, less than 32 weeks; birth weight, less than 1,500 g) were enrolled in the study. In eight infants in whom the serum Ca level declined to less than 6.0 mg/dL, changes in serum magnesium, phosphorus, PTH, CT, and whole blood ionized calcium (iCa) were evaluated on entry into the study, when serum Ca declined to less than 6.0 mg/dL, immediately after infusion of 18 mg/kg of elemental calcium as calcium gluconate, and at eight hours post-Ca infusion (+ 8 hr). The serum Ca concentration declined from 7.9 +/- 0.6 baseline (mean +/- SE) to 5.2 +/- 0.2 mg/dL pre-Ca infusion and rose to 9.17 +/- 0.74 mg/dL post-Ca infusion and 7.1 +/- 0.5 mg/dL at +8 hr post-Ca infusion. Whole blood iCa declined from 4.82 +/- 0.24 to 3.72 +/- 0.19 mg/dL pre-Ca infusion, rose to 6.68 +/- 0.32 mg/dL post-Ca infusion, and was 4.12 +/- 0.21 mg/dL at + 8 hr post-Ca infusion. The serum P concentration did not change significantly. The serum PTH concentration rose from 116 +/- 17 to 204 +/- 34 pmole/L pre-Ca infusion, declined to 149 +/- 22 pmole/L post-Ca infusion, and was 187 +/- 28 pmole/L at + 8 hr post-Ca infusion. The serum CT concentration was elevated and did not change significantly. Thus, in infants less than 32 weeks' gestation, the serum PTH level rises in early neonatal hypocalcemia and is suppressed by IV Ca infusion; the serum CT level is markedly elevated and is not altered in early neonatal hypocalcemia and does not rise further in response to IV Ca infusion in VLBW infants. We suggest that hypercalcitoninemia occurs in VLBW infants and that serum CT concentrations are unresponsive to changes in serum Ca. PMID- 4036927 TI - Pulmonary and renal responses to furosemide in infants with stage III-IV bronchopulmonary dysplasia. AB - Pulmonary and renal responses to furosemide were evaluated in ten infants with stage III-IV bronchopulmonary dysplasia. Furosemide was given intravenously for two doses, 1 and 2 mg/kg, at approximately 24-hour intervals. The following indices were evaluated in series before and after entry into study: clinical respiratory distress syndrome score; blood pH; partial pressure of arterial carbon dioxide; alveolar-arterial oxygen gradient; urine output; glomerular filtration rate; fractional excretion of filtered sodium, chloride, potassium, and calcium; osmolar clearance; water clearance; and concentrations of serum electrolytes and calcium. A significant decrease in the respiratory distress syndrome score and in the partial pressure of arterial carbon dioxide was seen only transiently at two hours following each dose. There was no significant improvement in the alveolar-arterial oxygen gradient during the study. Furosemide induced diuresis and urinary excretion of sodium, chloride, potassium, and calcium. A significant decrease in serum chloride and potassium concentrations was seen at 48 hours after entry into study; serum sodium and calcium concentrations remained unchanged. This study has demonstrated that furosemide administration has only a short-term effect in the lung but has a potential for long-term complication on electrolytes and calcium balance in infants with well established stage III-IV bronchopulmonary dysplasia. PMID- 4036928 TI - Risk factors associated with nosocomial rotavirus infection. AB - A prospective study of hospital-acquired rotavirus infection was undertaken on an infant and young toddler floor to assess the incidence of infection and risk factors associated with nosocomial transmission. During the seven-month study period, gastroenteritis accounted for 60 of 663 admissions, 23 (38%) of which were due to rotavirus. In spite of enteric isolation of 21 (91%) of 23 patients with community-acquired cases, 36 infants developed nosocomial rotavirus infections. The attack rate of hospital-acquired infection was 12.8%, ranging each month from 2% to 21%. Approximately three fourths of both community-acquired cases (17/23) and nosocomial cases (27/36) occurred during the late winter and early spring. Prolonged stays in the hospital were associated with an increased attack rate of rotavirus infection. The risk of nosocomial rotavirus infection was not significantly enhanced by room contact with a rotavirus-infected patient or by the sharing of staff. However, only 47% (17/36) of patients with nosocomial infections were appropriately isolated, despite symptoms of gastroenteritis in all cases. These findings indicate that hospital acquisition of rotavirus is common, and indicate that failure to isolate patients with nosocomial rotavirus infections could be an important factor in hospital transmission. PMID- 4036929 TI - The motor quotient. A method for the early detection of motor delay. AB - A motor quotient was calculated by dividing the age of a child's best motor achievement by his or her chronologic age. A quotient less than 50 was said to predict gross motor delay (walking at or later than 24 months). Applying the quotient to 144 8- to 18-month-old children yielded a sensitivity of 87%, specificity of 89%, and overreferral and underreferral rates of 12%. By viewing motor development as a ratio, one is able to forecast motor delay. PMID- 4036930 TI - The phantom earache. Temporomandibular joint dysfunction in children. AB - Temporomandibular joint dysfunction is a benign, relatively uncommon childhood disorder and should be considered in children who have intermittent unilateral otalgia of three to four days' duration and whose audiographic, tympanometric, and clinical otologic examinations reveal normal findings. Most of the patients in our study had undergone orthodontic therapy during the year preceding the onset of temporomandibular joint dysfunction, and the vast majority of them had received orthodontic treatment within two weeks of each episode of otalgia. The diagnosis can be confirmed clinically by reproducing the pain associated with masticatory muscle spasm by palpation of the preauricular areas, intraotic manipulation, and palpation of the pterygoid muscles. Treatment consists of administering acetaminophen, applying hot compresses to the preauricular area, and opening and closing the mouth 30 to 40 times after each compress as an effort to interrupt the muscle spasm. PMID- 4036931 TI - Hematogenous pelvic osteomyelitis in children. Clinical correlates of newer scanning methods. AB - The records of 18 children with hematogenous pelvic osteomyelitis seen over a four-year period were reviewed. The mean age of the patients was 7.8 years and their most common presenting symptoms were gait disturbance (present in 94%) and pain about the hip (61%) with only mild limitation of motion; 11 (61%) of 18 patients were afebrile at presentation. Although leukocytosis was uncommon, the erythrocyte sedimentation rate was almost always elevated (greater than 40 mm/hr in 94% of the patients). While initial plain roentgenograms were usually normal, gallium citrate Ga 67 and technetium Tc 99m oxidronate scintigrams were abnormal in all patients who underwent these studies. Computed tomography proved to be a useful complementary study to radionuclide scintigraphy, yielding positive findings in nine of 11 cases. Patients presented for medical care a median of 2.5 days after the onset of symptoms, whereas a longer period of time (median, 7.5 days) was required to establish the correct diagnosis after presentation for care. The only observed complications occurred in two patients in whom there was significant delay in institution of therapy. Prevention of complications from pelvic osteomyelitis lies in early recognition and appropriate treatment of the disease. In our experience, newer imaging techniques facilitate prompt diagnosis. PMID- 4036932 TI - Increased urinary excretion of renal N-acetyl-beta-glucosaminidase in hypercalciuria. AB - Urinary excretion of N-acetyl-beta-glucosaminidase (NAG), a lysosomal enzyme, was examined in 33 children with hypercalciuria. Urinary NAG excretion in 13 healthy children was 5.84 +/- 9.35 nmole/hr/mg of creatinine (NAG/Cr) (mean +/- SD) compared with 35.61 +/- 42.04 nmole/hr/mg of creatinine in 23 children with renal hypercalciuria, and 28.99 +/- 13.69 nmole/hr/mg of creatinine in ten children with absorptive hypercalciuria. In children with renal hypercalciuria, NAG/Cr excretion was not statistically different between children with either urolithiasis or hematuria without calculi. In six children with renal hypercalciuria, no significant change in NAG/Cr excretion occurred after a mean duration of 25 weeks of hydrochlorothiazide therapy although urinary calcium to creatinine ratios (UCa/Cr) decreased from 0.24 +/- 0.11 to 0.16 +/- 0.11. We conclude that increased urinary calcium excretion produces renal tubular injury and that the renal injury may not be reversed by short-term alterations in urinary calcium excretion. PMID- 4036933 TI - Agenesis of the corpus callosum. Clinical features in 40 children. AB - Forty children with partial agenesis of the corpus callosum have been prospectively identified and followed up for up to 15 years. Additional physical anomalies and diagnoses were frequent. At the time of diagnosis, the majority of children were developmentally delayed or retarded. If callosal agenesis was diagnosed during infancy, most children had or subsequently developed seizures. Older patients had a more favorable outcome and were less likely to develop epilepsy. PMID- 4036934 TI - Pneumatosis cystoides intestinalis and trichloroethylene exposure. AB - A case-control study was carried out to assess the association between pneumatosis cystoides intestinalis (PCI) and working conditions, including occupational exposure to organic solvents. Thirteen patients with primary PCI were individually matched with controls by sex, age, and admission year. It was found that there was a close association between the development of primary PCI and occupational exposure to trichloroethylene (TCE). Twelve of 13 patients with PCI (92.3%) were found to have been exposed occupationally to TCE, and the healing and recurrence of PCI in these patients substantially paralleled the profile of their occupational exposure to TCE. Two pairs of patients with PCI had been working in the same factories, where they had degreased camera lenses with TCE. These results suggest that chronic exposure to TCE could be one of the etiological factors in PCI. PMID- 4036935 TI - Ethanol, aspirin, ibuprofen, and the gastroduodenal mucosa: an endoscopic assessment. AB - The effect on the gastroduodenal mucosa of alcohol combined either with aspirin or ibuprofen was studied in 60 normal volunteers. The volunteers were divided into six groups comprised of 10 subjects receiving ibuprofen, placebo, or aspirin with or without alcohol. Medications consisted of 1) three 325-mg aspirin tablets, or three identical placebo tablets, 2) one 600-mg ibuprofen tablet, and 3), three ounces of 100 proof vodka diluted in 6 ounces of orange juice, or alcohol placebo made by diluting 3 ounces of water in orange juice. All subjects received 4 doses over a 24-hr period and underwent endoscopic examination the following morning. The gastroduodenal mucosa was graded according to a 0 to 4 + scale. Aspirin caused considerably greater duodenal and gastric damage than did either ibuprofen or placebo. The addition of alcohol to all drugs increased the damage seen in the stomach but not to a significant degree; this effect was slightly more pronounced with ibuprofen than with placebo or aspirin and approached significance (0.1 greater than p greater than 0.05). These results are compatible with alcohol being a mild damaging agent or a potentiating agent for damage from other drugs. PMID- 4036936 TI - Amyloid tumors of the gastrointestinal tract: a report of two cases and review of the literature. AB - Amyloid tumors of the gastrointestinal tract are exceedingly rare. Two cases are presented, one in the stomach of a patient who appeared to have systemic amyloidosis and one in the colon which appears to be isolated. The treatment was surgical excision. Extensive diagnostic work-up is required to evaluate the many various possible causes of amyloidosis. PMID- 4036937 TI - Intestinal obstruction caused by ingestion of a Heidelberg capsule: report of a case. AB - A case is reported in which a Heidelberg pH capsule was administered to a patient with the stenosing form of Crohn disease. The capsule impacted in the stricture resulting in small bowel obstruction ultimately requiring surgical intervention. The authors wish to emphasize that a careful history of preexisting intestinal disease should be taken before the administration of any nonabsorbable diagnostic device. PMID- 4036938 TI - Role of delayed indium-111 labeled leukocyte scan in the management of Crohn's disease. AB - Comparison of nine patients with Crohn's disease who had a positive delayed (24 hr) 111indium leukocyte scan and 10 patients with negative scan showed no significant difference between the two groups for the Crohn's disease activity index, sedimentation rate, survival, complications, number of days in hospital, outpatient visits, or readmissions. Despite the apparent lack of statistical significance in Crohn's disease activity index, the scan was positive in nine of 16 patients with a Crohn's disease activity index more than 150, and none of three patients with Crohn's disease activity index less than 150. In the patients studied, there were no false-positive leukocyte scans. In nine of 10 patients with ileocolonic disease, scanning results correctly predicted the proper management. Six patients with positive scan and enteroclysis responded to medical treatment. Four patients had positive enteroclysis and negative scan; of these, three had radiographic features of chronic ileal stricture which was confirmed at operation. The results suggest that a negative delayed indium-111 leukocyte scan may be useful in diagnosis of chronic fibrotic ileal stricture. PMID- 4036939 TI - Pharmacokinetic study on the hepatic uptake of indocyanine green in cirrhotic patients. AB - The mechanism by which the mean blood clearance (CLtot,B) of indocyanine green (ICG) was reduced in cirrhotic patients was examined pharmacokinetically. It was demonstrated that the reduction in the CLtot,B of ICG in cirrhosis would be mainly due to the decrease in the hepatic uptake clearance and partly due to the increase in the efflux clearance from the liver to plasma. It is suggested that the decrease in the hepatic uptake clearance in cirrhosis mainly reflects the decrease in the intrinsic clearance of hepatic uptake rather than the decrease in hepatic blood flow. PMID- 4036940 TI - Spontaneous neuroma of the bile duct: a case report. AB - We report on a 65-year-old man with a stenosis of the bile duct which was caused by spontaneous neuroma, with no history of laparotomy. Although he had a gallstone and slightly abnormal parameters on liver function tests, he had no known history of abdominal pain or jaundice. This is a very rare case of a benign stenosis of the common bile duct. PMID- 4036941 TI - Hydatid cyst of the liver rupturing into the biliary tract--mimicking acute cholecystitis on hepatobiliary scanning. AB - Two patients presenting with right upper abdominal colicky pain, jaundice, and fever had a hepatobiliary scan using Tc 99m HIDA. The scan was suggestive of acute cholecystitis and a space occupying lesion in the liver. On operation, liver echinococcosis, located in the right lobe rupturing into the biliary ductal system, was found. Intraoperative cholangiography revealed filling defects in the main biliary ducts. Exploration of the common bile duct disclosed daughter cysts and cystic debris. Acute cholecystitis or stones were not found. We conclude that in patients with a clinical picture and HIDA scanning compatible with acute cholecystitis and a space occupying lesion in the liver, the diagnosis of hydatid cyst of the liver which has ruptured into the biliary tract should be considered. PMID- 4036942 TI - Mirizzi syndrome. AB - A 56-year-old woman was admitted to the hospital because of icterus and pruritus of 1 month duration. During her evaluation, endoscopic retrograde cholangiography revealed large cystic duct stones causing partial obstruction of the common hepatic duct. Successful management was accomplished with choledochojejunostomy and T-tube decompression. The case herein reported illustrates the typical clinical presentation and radiographic features of the Mirizzi syndrome. PMID- 4036943 TI - Abstracts submitted for 50th annual scientific meeting, American College of Gastroenterology. October 9-11, 1985. Miami Beach, Florida. PMID- 4036944 TI - The effects of swallowing frequency and transdermal scopolamine on esophageal acid clearance. AB - Fourteen volunteers were studied on two occasions to assess the effect of swallowing frequency on acid clearance time. The experimental protocol consisted of two trials of infusion of 15 ml of 0.1 N HCl into the distal esophagus. One trial required swallowing every 30 s for 10 min. The other trial involved an initial rapid swallowing rate (seven swallows in the 1st min) with a gradual predetermined decline in rate. This procedure was repeated 12 h after application of a transdermal scopolamine patch. Baseline clearance times for rapid and slow swallowing were not significantly different. The anticholinergic drug significantly prolonged the clearance times for both rapid and slow swallowing. Under baseline conditions, sequential swallows (after the first three to four swallows) produced a significant rise in pH until the clearance criterion of pH 4.0 was reached. This effect was abolished with the anticholinergic drug. These results support a two-stage model of acid clearance with initial volume clearance and subsequent salivary buffering of residual intraesophageal acid. PMID- 4036945 TI - Physiopathological heterogeneity of the duodenal mechanisms that inhibit gastric acid secretion in duodenal ulcer patients. AB - The effect of duodenal acidification on pentagastrin-stimulated gastric acid secretion was studied in 43 duodenal ulcer patients and in 17 normal controls. Three types of responses were observed: group A, no inhibition of gastric acid secretion occurred in 17 (40%) ulcer patients and in three (18%) controls (p less than 0.05); group B, inhibition of gastric acidity occurred in seven (16%) ulcer patients and in 12 (71%) controls (p less than 0.05), and group C, retarded gastric acid inhibition occurred in 19 (44%) duodenal ulcer patients and in 2 (12%) controls (p less than 0.05). Secretin levels did not increase after duodenal acidification, the higher percentages of failure being observed in groups A and C (p less than 0.05). The pH of the duodenal aspirate was 4.9 +/- 2 and 7.7 +/- 1.4 in ulcer patients and controls, respectively (p less than 0.05), with the low levels being detected in groups A and C (4.7 +/- 2 and 5.3 +/- 2.1) compared to group B (7.3 +/- 1.7; p less than 0.05). The results show that responses of duodenal ulcer patients to duodenal acidification are heterogeneous, and that failure of gastric secretion inhibition and defective intraduodenal acid neutralization are related. PMID- 4036946 TI - Sorbitol intolerance in adults. AB - Sorbitol is a commonly used sugar substitute in "sugar-free" food products. Although sorbitol intolerance manifested by abdominal pain, bloating, and diarrhea has been observed in children, it has not been well documented in adults. Forty-two healthy adults (23 whites, 19 nonwhites) participated in this study. After ingestion of 10 g of sorbitol solution, end expiratory breath samples were collected at 15-min intervals for 4 h and analyzed for H2 concentration. Clinical sorbitol intolerance was detected in 43% of the whites and 55% of the nonwhites, the difference not being statistically significant. However, severe clinical sorbitol intolerance was significantly more prevalent in nonwhites (32%) as compared to whites (4%). There was a good correlation between the severity of symptoms and the amount of hydrogen exhaled. Dietetic foods, many of them containing sorbitol, are very popular with diabetics and "weight watchers." Based on our observations, we believe that a large number of adults could be suffering from sorbitol-induced nonspecific abdominal symptoms and diarrhea. These symptoms could lead to an extensive diagnostic work-up and lifelong diagnosis of irritable bowel syndrome. PMID- 4036947 TI - Ventricular fibrillation during colonoscopy: case report and review of the literature. AB - We report a case of ventricular fibrillation during colonoscopy in a patient with stable anginal syndrome. Review of the literature and mechanisms of arrhythmia are discussed. PMID- 4036948 TI - Endoscopic laser symposium. PMID- 4036949 TI - Practical considerations of endoscopic laser therapy. AB - Endoscopic laser therapy in an institution requires commitment to ongoing education and service. Cooperation of physicians and hospital administration, along with acceptance by the public, is essential. Planning for equipment, personnel, space, operational procedures, safety, and cost is vital. Requirements for a functional laser unit are discussed. The case distribution for the initial 7 months of operation in the Greenwich Hospital Laser Center is presented. PMID- 4036950 TI - Endoscopic laboratory with laser: organization, safety, and equipment. AB - The purpose of this paper is to acquaint potential laser users with important practical and technical aspects involved in establishing laser programs in a community hospital. Included are considerations of equipment, space, safety, staffing, training, and organization. PMID- 4036951 TI - Tumor ablation by endoscopic Nd:YAG laser. AB - Nd:YAG laser ablation of tumors of the gastrointestinal tract is reviewed. Techniques used and problems encountered in the ablation of obstructive tumors is discussed and illustrative cases of esophageal and rectal tumor treatment with laser using a lumen guide are presented. The improvement in quality and dignity of life for patients receiving laser ablation therapy for obstructing tumors of the esophagus and colon is demonstrated. PMID- 4036952 TI - Laser treatment of esophageal cancer. PMID- 4036953 TI - Esophageal moniliasis: a new radiographic presentation. AB - A previously unreported manifestation of esophageal moniliasis is described. Two patients with acquired immunodeficiency syndrome and Kaposi's sarcoma presented with solitary esophageal ulcers. Endoscopic biopsy confirmed the clinical diagnosis of esophageal moniliasis. The clinical and radiographic features of esophageal moniliasis are described. PMID- 4036954 TI - Lessons from the Japanese. PMID- 4036955 TI - Enzyme activities of cultured erythroblasts. AB - The enzyme activities of cultured early erythroid progenitor cells (burst-forming unit erythroid, BFU-E) were measured and were compared with the activities of mature erythrocytes. The enzyme activity of acetylcholinesterase was not detectable in the erythroblasts. The ratios of phosphofructokinase and glutathione peroxidase were low due to low enzyme activities in both the erythroblasts and erythrocytes. The ratios of triose phosphate isomerase, phosphoglycerate kinase, and adenylate kinase were low due to high enzyme activities in both the erythroblasts and erythrocytes. The ratios of hexokinase, glucose phosphate isomerase, monophosphoglyceromutase, pyruvate kinase, and adenosine deaminase were high due to high enzyme activities in the erythroblasts. The isozyme of erythroblast hexokinase was of the prototype isozyme I, while pyruvate kinase was predominantly of the prototype M2, with two hybrid isozymes to the anodal side by electrophoresis. These facts suggest that there is a greatly different metabolic pattern during the maturation of the erythroid cells. PMID- 4036956 TI - The laboratory use of butylnitrite for the production of methemoglobin. AB - The use of volatile butylnitrite in place of sodium nitrite for the in vitro production of methemoglobin was explored in studies of G6PD-deficient red cells and for measurements of the red cell methemoglobin reductase activity. It was found that butylnitrite vapor caused a more rapid oxidation of intracellular hemoglobin than sodium nitrite and required fewer washes for removal. Hence a more rapid preparation of the cells was possible. Both cytochemical detection of G6PD-deficient cells in a female heterozygote for G6PD deficiency and the screening test for a methemoglobin reductase deficiency could be performed with butylnitrite as well as with sodium nitrite. This small modification of these standard procedures promises to save time and facilitate processing of many samples during genetic screening of relevant populations. PMID- 4036957 TI - Terminal deoxynucleotidyl transferase-positive acute leukemias evolving from a myelodysplastic syndrome. AB - We have analyzed the distribution of terminal deoxynucleotidyl transferase (TdT) in 30 patients with myelodysplastic syndromes (MDS), in connection with morphology, cytochemistry, and cytogenetics. All cases in preleukemic phase were strictly TdT-negative. At variance, 4 (19%) of 21 cases with subsequent leukemia were TdT-positive and showed a pure lymphoid (one case) or a mixed lymphoid myelomonocytic (three cases) morphology. The TdT enzymatic activity ranged from 2 to 21 U/10(8) cells and the percent of positive cells in the immunofluorescence test ranged from 10 to 80% of total. All cases were Philadelphia chromosome negative. The clonal origin of MDS from the pluripotent stem cell, capable of originating both a lymphoid and myeloid progeny, is further corroborated. PMID- 4036958 TI - Low-dose arabinosyl cytosine in acute leukemia after a myelodysplastic syndrome and in elderly leukemia. AB - Low-dose arabinosyl cytosine (ARA-C) was tested in 15 patients with acute leukemia after a myelodysplastic syndrome (MDS) and in six elderly patients with acute nonlymphoid leukemia (ANLL). The drug was given subcutaneously at 10 mg/m2, every 12 hr for 2 weeks, every 28 days. The overall response rate was 19% (one complete remission, three partial responses), and the median duration of response was 4 months. No particular features at diagnosis were predictive of response. Pancytopenia and marrow hypoplasia occurred after 44 (78%) of 56 courses of therapy and were more severe in nonresponders. Four patients died during the aplasia following ARA-C therapy. Subcutaneous low-dose ARA-C was of limited benefit and bore a noticeable hematologic toxicity. PMID- 4036959 TI - Long-term effect of uninephrectomy on serum creatinine concentration and arterial blood pressure. AB - Medical records of patients having unilateral nephrectomies done between 1953 and 1978 at a university hospital were reviewed after 5 to 30 years of follow-up to determine if this procedure causes insidious renal insufficiency. Forty patients (selected from 571) ranging in age from 20 to 72 years met the following criteria for inclusion in the study: subject over 20 years of age at nephrectomy; initial serum creatinine concentration less than 1.6 mg/dL; normal arterial blood pressure (less than 150/90 mm Hg); absence of risk factors for chronic renal disease, eg, systemic lupus erythematosis, diabetes mellitus, chronic glomerulonephritis; an initial and a follow-up serum creatinine level; at least 5 years of follow-up. After a mean follow-up of 11.8 years, paired analysis of changes in serum creatinine concentrations showed insignificant differences between pre- and post-nephrectomy levels (0.19 +/- 0.11 mg/dL +/- SEM). Only one patient had a post-nephrectomy serum creatinine level above 2.0 mg/dL. Six patients (four women, two men) developed hypertension (15%) after uninephrectomy, an incidence of hypertension not greater than that found in the population at large. We conclude that uninephrectomy at ages older than 20 years does not lead to renal insufficiency or hypertension in adult patients with normal prenephrectomy serum creatinine and blood pressure levels. PMID- 4036960 TI - Serum and dialysate concentrations of cephalexin following repeated dosing in CAPD patients. AB - Oral cephalexin, 1 to 2 g daily for 3 days, was given to six stable, noninfected patients receiving maintenance continuous ambulatory peritoneal dialysis (CAPD). The peak serum concentration after a 2 g initial dose was between 73 and 123 mg/L. On the second and third day in five patients who received a 2 g daily oral dose, the serum concentrations were between 35 and 118 mg/L in serum obtained 1 to 1.5 hours after the dosing. Similar serum concentrations were seen in one patient who only received a 1 g oral dose on the second and third day. Cephalexin concentrations in the peritoneal dialysate reached a peak on the first day between 4 to 14 hours after the dose and were between 31 to 78 mg/L. During the second and third day, the highest cephalexin concentration was 118 mg/L and the lowest was 12 mg/L. The data are consistent with the feasibility of oral cephalexin for treatment of CAPD-associated peritonitis with microorganisms that are sensitive to these levels of cephalexin. PMID- 4036961 TI - Cryoglobulinemia and immune-mediated glomerulonephritis in association with hairy cell leukemia. AB - The nephrotic syndrome in association with hairy cell leukemia is typically seen in the setting of amyloidosis. This report describes a patient with the nephrotic syndrome and hairy cell leukemia in whom cryoglobulinemia and an immune-mediated glomerulonephritis were seen. While hairy cells have the capacity for immunoglobulin production, we were unable to demonstrate a teleological link between these cells and the renal lesion. In contrast, there is speculative evidence to suggest that indolent infections may have played a causative role in cryoglobulin production and the subsequent immune-mediated glomerulonephritis. PMID- 4036962 TI - Peritoneo-venous shunting in patients with cirrhotic ascites and end-stage renal failure. AB - End-stage renal failure supervened in two cirrhotic patients with ascites, necessitating maintenance hemodialysis therapy. One patient had a functioning LeVeen peritoneo-jugular shunt (Becton-Dickinson, Rutherford, NJ) in place at the time that hemodialysis was initiated. In the other patient, a LeVeen shunt was inserted 8 months after beginning hemodialysis, after extracorporeal ultrafiltration had failed to resolve his ascites. Both patients achieved control of their ascites and enjoyed relatively long survival. Our results suggest that, in patients with cirrhotic ascites who develop end-stage renal failure, successful long-term management can be obtained using a combination of peritoneo venous shunting and maintenance hemodialysis. PMID- 4036963 TI - Development of a shared database for drug information in the United Kingdom. PMID- 4036964 TI - Personal letters to physicians about nonformulary drug orders. PMID- 4036965 TI - Industrial pharmacy residency. PMID- 4036967 TI - Ethics and integrity of the drug supply. PMID- 4036966 TI - Names for PEG-electrolyte lavage solutions. PMID- 4036968 TI - Research--the cornerstone of pharmacy practice. Harvey A.K. Whitney lecture. AB - Hospital pharmacy's need for a new commitment to research and the attendant sharing of responsibilities between pharmacy educators and pharmacy practitioners are described. Guided by the same philosophy of professional service that motivated early hospital pharmacists, individual pharmacists should work within their differentiated roles to advance the profession as a whole. For this advancement, research to acquire new knowledge and develop and evaluate new services is required. Research enhances the prestige and societal support of a profession. Pharmacists with differentiated skills and practice areas must support each other to advance the profession, particularly because of limited financial resources in both education and practice settings. Universities, including schools of pharmacy, have a responsibility for research as well as for the transmission of knowledge, and pharmacy faculty members should conduct research that supports the advancement of practice. To support research by faculty members, pharmacy practitioners can assume greater teaching responsibility. Schools of pharmacy and practicing pharmacists can work together to support research that will benefit the whole profession and society. Pharmacy practice faculty members who maintain a practice base and are involved in research have a critical role in this cooperative effort. PMID- 4036969 TI - An interdisciplinary method of classifying and monitoring medication errors. AB - A system is described for reporting medication errors according to practitioner and type and using these data as part of a departmental quality-assessment program. Types of errors committed in prescribing, in dispensing, and in administering drugs in a teaching hospital were listed. Prescribers' and pharmacists' reports of errors committed. Data on dispensing errors by 16 staff pharmacists were collected over a 12-month period in 1982-83, and data on prescribing by resident physicians were collected during three separate one-month periods. For each pharmacist, data on dispensing errors were compiled monthly. Pharmacists were counseled if they had a large number of errors in one category, a high total number of errors, or a substantial number of errors in a single category over several months. Likewise, physicians who committed more errors than their department's mean were counseled by the clinical chairman. After 12 months, each pharmacist's monthly error rate was compared with the departmental average. The number of dispensing errors reported during the study period (average 60.7 per month for the department) was lower than expected. Serious prescribing errors were minimal. In spite of probable underreporting of errors in this voluntary system, these methods of classifying medication errors by type and practitioner group and of recording error rates were useful tools for monitoring and improving performance of pharmacists and prescribers. PMID- 4036970 TI - Operation of an allergen-extract pharmacy. AB - The quality control (QC) and quality assurance (QA) systems for a military allergen-extract pharmacy are described. The United States Army Allergen Extract Laboratory (USAAEL) provides diagnostic and therapeutic allergen-extract materials to military personnel throughout the world. More than 40,000 individualized prescriptions are compounded annually. The staff is composed of one pharmacist, 16 medical technicians, and four clerical, two inventory, and three supervisory personnel. Each prescription takes about one man-hour to prepare. The technicians are trained in aseptic technique, allergen-extract compounding, and the diagnosis and treatment of allergies during an eight-week program. Following a physician-allergist's evaluation of a patient, a prescription is written with a formula itemizing the specific allergen components, their relative concentrations, and a treatment schedule. Patient profile cards are kept on every patient. A complete record of patient, prescriber, demographic data, allergen formula, treatment schedule, lots, and initials of personnel responsible at each step allow a thorough assessment for QC and QA. The identity and volume of each allergen in every prescription are checked twice. A multitiered QC system is used to identify problems and errors. A QA and QC assessment was conducted on more than 18,000 prescriptions received during a six-month period. More than 99% of all known errors were discovered before the prescriptions were dispensed. Allergen-extract prescriptions must be accurate, precise, and reproducible to be effective and to avoid adverse reactions. Pharmacists can play a vital role in ensuring the optimal quality of diagnostic and therapeutic allergen extracts. PMID- 4036971 TI - Osmolality of small-volume intravenous admixtures. AB - Osmolalities of commonly administered small-volume i.v. admixtures were determined, and use of diluents with lower osmolality to achieve osmolality values less than 400 mOsm/kg was studied. The theoretical osmolality of 218 hypothetical admixtures of various concentrations of 34 injectable drugs in 50- or 100-mL quantities of 5% dextrose injection or 0.9% sodium chloride injection was calculated using sodium chloride equivalents. If the calculated osmolality value was greater than 400 mOsm/kg, an actual admixture was prepared and osmolality and density were measured. To determine how admixtures with osmolality values less than 400 mOsm/kg could be prepared, theoretical osmolality was calculated using 0.45% sodium chloride injection or sterile water for injection as the diluent. The calculated osmolality value was greater than 400 mOsm/kg for 52 (23.9%) of the 218 admixtures tested. Of the 52 measured osmolality values, 47 were within 15% of the calculated value. Calculated osmolality values for all admixtures were less than 400 mOsm/kg when 0.45% sodium chloride injection or sterile water for injection was used as the diluent. Admixture osmolality should be considered when preparing drugs for i.v. injection. For drugs with high osmolalities, 0.45% sodium chloride injection or sterile water for injection may be used as the diluent. PMID- 4036972 TI - Cost savings associated with use of gentamicin versus tobramycin. AB - A hospital's use and costs of tobramycin sulfate versus gentamicin sulfate before and after a tobramycin use review were compared. Retrospective audits of 100 charts of adult patients in a 515-bed hospital were performed for two six-month periods in 1983-84. Tobramycin use was considered appropriate in patients with serum creatinine concentrations greater than 1.5 mg/dL or pre-existing renal disease, in any patient over 70 years of age, and in patients with neutropenia, documented pseudomonas infection, or infection with an organism shown to be resistant to gentamicin but sensitive to tobramycin. Tobramycin use was not justifiable in 37 (18.7%) of 198 patients whose charts were evaluable. Use of gentamicin in these 37 patients would have saved $14,300. The infection control committee was notified of the audit results; the audit results and recommendations for tobramycin use were included in a letter to all physicians; and the infectious disease service held educational conferences on tobramycin use. In the first six months after the corrective measures, mean monthly tobramycin use decreased by 38% and gentamicin use increased by 48.9%. Total aminoglycoside costs decreased 30.2% and total aminoglycoside use decreased 12.5%. In the second six months after intervention, mean monthly tobramycin use was 11% less than before intervention, and mean monthly gentamicin use was 13% greater than before intervention. Total aminoglycoside costs were 3.6% less and total aminoglycoside use was 4% less than before the audit. The tobramycin use audit and subsequent interventions with prescribers were effective in reducing tobramycin use and costs for approximately six months; decreases in tobramycin use and costs were smaller during the second six months after intervention. PMID- 4036973 TI - Stability of mitomycin admixtures. AB - The stability of mitomycin in admixtures for continuous intravenous infusion was studied. Mitomycin was reconstituted and diluted to 50 micrograms/mL in polyvinyl chloride minibags containing 5% dextrose injection 50 mL or 0.9% sodium chloride injection 50 mL. Additional mitomycin admixtures were reconstituted with a buffer solution containing monobasic and dibasic sodium phosphate; these were diluted with 5% dextrose injection only. Admixtures were stored at room temperature (27 30 degrees C) and refrigerated temperature (5 degrees C) for 120 days. Mitomycin concentrations in each admixture were tested by high-performance liquid chromatography (HPLC) immediately after admixture and at intervals during storage. Ultraviolet spectra were determined at the same time as HPLC analysis, and the admixtures were visually inspected and tested for pH. Mitomycin concentrations decreased rapidly in the unbuffered admixtures; after 12 hours at room temperature, less than 26% of the drug remained in the dextrose admixture. When the unbuffered admixtures were refrigerated for 12 hours, the mitomycin concentrations decreased 10% in the sodium chloride admixtures and 33% in the dextrose admixtures; after 24 hours, the percentages of drug loss were 23% and 42%, respectively. Mitomycin concentrations in the buffered admixtures showed no substantial decrease during 120 days at 5 degrees C. At room temperature, concentrations decreased 10% after 15 days. When the admixture is buffered to a pH of approximately 7.8, mitomycin is stable in 5% dextrose injection for up to 15 days at room temperature and at least 120 days at 5 degrees C. Unbuffered mitomycin admixtures should not be stored or administered by prolonged i.v. infusion. PMID- 4036974 TI - Diabetes dialogue: the spectrum of defects in non-insulin-dependent diabetes mellitus. PMID- 4036975 TI - Multicenter collaborative evaluation of a standardized serum bactericidal test as a prognostic indicator in infective endocarditis. PMID- 4036976 TI - Runner's macrocytosis: a clue to footstrike hemolysis. PMID- 4036977 TI - What is the art of medicine? PMID- 4036978 TI - Cost containment in an equilibrium state. PMID- 4036979 TI - Correction of hypocitraturia and prevention of stone formation by combined thiazide and potassium citrate therapy in thiazide-unresponsive hypercalciuric nephrolithiasis. AB - Thirteen patients with hypercalciuric calcium nephrolithiasis continued to form calcium stones when treated with thiazide (4.69 +/- 6.62 [mean +/- SD] stones per patient-year to 5.12 +/- 10.87 stones per patient-year), despite adequate hypocalciuric response (a reduction in urinary calcium levels from 303 +/- 119 mg per day to 193 +/- 88 mg per day, p less than 0.01). Because they had hypocitraturia (250 +/- 86 mg per day versus 643 +/- 236 mg per day in normal subjects, p less than 0.001), potassium citrate (10 to 20 meq three times per day) was added to the ongoing treatment program. During combined treatment with thiazide and potassium citrate, urinary pH significantly rose, and normal levels of urinary citrate were restored. Ten patients stopped forming new stones and all 13 had reduced stone formation rate. Thus, potassium citrate supplementation should be considered in patients requiring thiazide therapy for the control of hypercalciuric nephrolithiasis, especially if they have concurrent hypocitraturia or if it develops during thiazide therapy. PMID- 4036980 TI - Clinical significance of the elevated anion gap. AB - To determine the clinical significance of a high anion gap (more than 16 meq/liter), consecutive patients in whom electrolyte determinations were made in an emergency room and who had either a normal (8 to 16 meq/liter) (n = 571) or a high (n = 100) anion gap were contrasted. No differences were noted between the groups with regard to age or length of stay in the hospital, but in the group with a high anion gap, there was an increased severity and frequency of multiple electrolyte disorders, and higher general admission rates (66 percent with high anion gap versus 51 percent with normal anion gap, p less than 0.02), rates of admission to an intensive care unit (25 percent with high anion gap versus 14 percent with normal anion gap, p less than 0.03), and mortality within one week of admission (12 percent with high anion gap versus 0.5 percent with normal anion gap, p less than 0.001) as compared with the group with a normal anion gap. Notably, patients without severe electrolyte abnormalities and a high anion gap had higher admission rates and a 50-fold increased mortality rate as compared with the group without severe electrolyte disturbances and a normal anion gap. Thus, an elevated anion gap is associated with an increased severity of illness that is independent of concomitant severe electrolyte abnormalities. Patients with a normal or high anion gap that survived the first week of hospitalization were shown to have an extremely low risk for mortality. PMID- 4036981 TI - Plasma cell dyscrasia with marrow fibrosis. Clinicopathologic syndrome. AB - Five new cases of plasma cell dyscrasia with coexistent myelofibrosis are described and six previously reported cases are reviewed. Four of the new patients and two from the literature had features of a previously unrecognized syndrome. This syndrome was characterized by significant paraprotein levels, marked marrow fibrosis, and plasmacytosis, without features of extramedullary hematopoiesis (agnogenic myeloid metaplasia) and leukoerythroblastosis. These patients were generally severely anemic and commonly leukopenic and thrombocytopenic. In contrast, one of the new patients and four in the literature showed classic features of the myeloproliferative disease, myelofibrosis with agnogenic myeloid metaplasia, along with features of typical multiple myeloma. PMID- 4036982 TI - Polymyalgia rheumatica. Duration of therapy and long-term outcome. AB - The duration of therapy and outcome were examined in 76 patients with polymyalgia rheumatica without evidence of temporal arteritis at presentation. Seventy-five patients received corticosteroids, with a mean prednisone dosage of 22.8 mg per day initially. Duration of therapy was assessed using life-table methods. No significant difference could be ascertained between groups segregated on the basis of age, sex, or initial steroid dosage. The median duration of therapy was 37.3 months. It was estimated that 40 percent of patients will require therapy longer than four years. Corticosteroids were permanently discontinued in 31 patients after a mean of 23.7 months of therapy. The data support the concept of two patient populations--one with limited disease and another requiring long-term therapy. Relapses were frequent, occurring in 56 percent of patients. Evolution of arteritis during the course of therapy was infrequent, occurring in only one patient. Steroid-related adverse effects occurred in 22.7 percent of patients and were more common in females. The data suggest that, although corticosteroids may be discontinued in some patients with polymyalgia rheumatica, prolonged therapy is required in a significant number. PMID- 4036983 TI - Adverse effects due to morphine sulfate. Challenge to previous clinical doctrine. AB - Despite a lack of clinical data in this area, conventional wisdom holds that morphine sulfate induces vagally mediated conduction defects, especially in patients with inferior myocardial infarction. To assess the accuracy of this "clinical pearl," the records of 244 patients admitted to the Barnes Hospital Cardiac Care Unit with suspected acute myocardial infarction were reviewed to determine the frequency of deleterious cardiovascular effects related to the administration of morphine sulfate. Of 184 patients (156 subsequently documented to have infarction) who received morphine sulfate, four patients had symptomatic hypotension temporally associated with morphine sulfate administration. This represented a frequency of 2.2 percent for all patients treated with morphine sulfate and a frequency of 2.6 percent in those with proved infarction. In each instance, the heart rate response was inappropriate, i.e., decreased or less markedly accelerated than might be expected given the reduced blood pressure, suggesting a vagal mechanism for the adverse effects. Only one of the four patients had inferior infarction, and in three of four instances, the adverse effect occurred after the first dose. All patients subsequently received morphine sulfate without evidence of toxicity. No case of narcotic-induced conduction abnormality was identified. This series, which is the most extensive evaluation of the topic, documents that adverse cardiovascular effects due to morphine sulfate are rare and do not conform to preconceived clinical doctrine. They consist of inappropriate heart rate responses to hypotension rather than conduction defects and are not particularly associated with inferior myocardial infarction. PMID- 4036984 TI - Low-dose methotrexate treatment of rheumatoid arthritis. Long-term observations. AB - Of 21 patients with rheumatoid arthritis who began to receive low-dose weekly methotrexate up to five years ago, 15 (71 percent) have continued to take this drug for a mean of 42 months and have received a mean total dose of 2,021 mg (range: 915 to 3,075). The clinical improvement noted at the first follow-up (11 months) was sustained throughout this follow-up period (42 months). Three patients (14 percent) have had complete clinical remission and nine others (43 percent) have had an excellent response. Methotrexate was discontinued in four patients between the first and second follow-up because of planned pregnancy (one), gastrointestinal toxicity (two), and fear of toxicity (one). Liver toxicity assessed in these 21 patients and four others receiving long-term methotrexate therapy revealed acute hepatitis in one and elevated transaminase levels in 12 (48 percent). Liver biopsy specimens in 17 patients after a mean of 1,950 mg of methotrexate (range: 915 to 3,125) revealed mild fibrosis in six and no cirrhosis. Methotrexate can continue to suppress rheumatoid synovitis over a prolonged period of time with minimal toxicity in most patients. Hepatic fibrosis and cirrhosis due to methotrexate may be less common in rheumatoid arthritis than has been reported in psoriasis. PMID- 4036985 TI - The carcinoid syndrome: comparison of 21 necropsy subjects with carcinoid heart disease to 15 necropsy subjects without carcinoid heart disease. AB - Carcinoid heart disease is a morphologically specific type of cardiac disorder that involves the mural and valvular endocardium on the right side of the heart. Twenty-one subjects (57 percent) (Group I) with carcinoid heart disease and 15 subjects (43 percent) (Group II) without carcinoid heart disease were studied at necropsy. The two groups were similar in mean age (54 years versus 55 years), duration of clinical illness (4.7 years versus 6.3 years), body weight (50 kg versus 52 kg), systemic blood pressure (117/77 mm Hg versus 128/77 mm Hg), blood hematocrit levels (37 percent versus 36 percent), total serum protein levels (6.0 g/dl), and serum albumin levels (2.2 g/dl versus 2.6 g/dl). The two groups were different in the frequency of the presence of precordial murmurs consistent with tricuspid regurgitation and/or pulmonic stenosis (95 percent versus 13 percent), cardiomegaly by chest radiography (38 percent versus 0), low voltage on electrocardiography (47 percent versus 0), and location of the primary site of the carcinoid tumor. Total electrocardiographic 12-lead QRS voltage was similar in each group (105 mm versus 132 mm) (10 mm = 1 mV). Of Group I subjects, 43 percent died of cardiac causes; none of the Group II subjects died of cardiac causes. Of the 21 subjects with carcinoid heart disease, seven had left-sided cardiac involvement, but in none was it of functional significance. Thus, although carcinoid heart disease frequently is the cause of death in patients with the carcinoid syndrome, the development of carcinoid heart disease is not related to the duration of symptoms of the carcinoid syndrome. PMID- 4036986 TI - Inflammatory carcinoma of the breast. Clinical review and summary of the Vanderbilt experience with multi-modality therapy. AB - Inflammatory breast cancer is a distinct clinicopathologic entity that accounts for 1 percent of all cases of breast cancer. The diagnosis should be strongly suspected on the basis of the distinctive clinical findings, which include edema of the breast, inflammation, wheals, and a typical reddish-purple color of the overlying skin. Pathologic examination usually shows infiltration of the dermal lymphatics with carcinoma. Evidence of distant metastatic spread is more frequent than with other types of breast cancer and is seen in approximately 30 percent of patients. The five-year disease-free survival rate is less than 5 percent when local therapy alone (mastectomy and/or local radiotherapy) is used. The addition of combination chemotherapy to high-dose local radiotherapy has improved the five year survival rate to approximately 30 percent. The potential for long-term survival is limited to the subgroup of patients with only local-regional disease at the time of diagnosis. Patients with inflammatory breast cancer should be treated with combined-modality therapy using combination chemotherapy and high dose radiotherapy to the breast, since this approach is potentially curative. The fatalism formerly associated with this diagnosis is no longer warranted, particularly in patients with local-regional disease. Failure to employ intensive combined-modality treatment will deny some patients a chance for long-term survival. PMID- 4036987 TI - Fever of unknown origin in a 71-year-old woman. PMID- 4036988 TI - Pituitary apoplexy, the Houssay phenomenon, and accelerated proliferative retinopathy. AB - A 42-year-old man with diabetes mellitus and probably acromegaly had a pituitary apoplexy with left-sided oculomotor palsy. There was an immediate fall in blood glucose concentration. Pituitary insufficiency promptly developed. Blood glucose levels remained normal for the next two years. During the first year after the pituitary apoplexy, severe proliferative retinopathy developed in the left eye, which became almost blind. Only mild retinopathy was present on the right side. Plasma concentrations of growth hormone remained low after the apoplexy, and the acromegalic features subsided. The explanation of these findings may be that the proliferative retinal angiopathy was caused by compression of the cavernous sinus at the time of the apoplexy. This would lead to impaired venous drainage, thus resembling occlusion of the central retinal vein, which may cause retinopathy similar to that seen in diabetes mellitus. PMID- 4036989 TI - Constrictive pericarditis after myocardial infarction. Sequela of anticoagulant induced hemopericardium. AB - Hemopericardium developed following adequate (and not excessive) anticoagulation in a patient with acute transmural anterior myocardial infarction and an early pericardial friction rub. Drainage of a bloody effusion by pericardiocentesis did not prevent progression to constrictive pericarditis within one year. The clinical features of this case and of the only two other similar occurrences reported in the medical literature are described and lead to a discussion of therapeutic and preventive measures. PMID- 4036990 TI - Fibrinolysis and acquired alpha-2 plasmin inhibitor deficiency in amyloidosis. AB - A patient with plasma cell myeloma and amyloidosis presented with a severe bleeding disorder. There was laboratory evidence of fibrinolysis and severe deficiency of alpha-2 plasmin inhibitor. Treatment with epsilon aminocaproic acid was associated with diminished bleeding and marked increase in the plasmin inhibitor level. This is the first report of acquired alpha-2 plasmin inhibitor deficiency in the fibrinolytic state associated with amyloidosis. PMID- 4036991 TI - Listeriosis in patients with long-term hemodialysis and transfusional iron overload. AB - Over a four-year interval, four cases of Listeria monocytogenes bacteremia were observed among a population of 127 patients undergoing long-term hemodialysis. None had an underlying malignancy or were recently receiving immunosuppressive medications. A search for a predisposing factor suggested a relationship to transfusional iron overload. Although still a rare infection, the possibility of listeriosis must be kept in mind by physicians caring for patients undergoing hemodialysis, particularly those requiring blood transfusions. PMID- 4036993 TI - Family acceptance of home apnea monitors. AB - Home monitoring for apnea patients has been called a stressful situation for family members. A 28-item questionnaire was used to ascertain the impact of home monitoring on the families of children with infantile apnea. Forty of 71 families returned the questionnaire. The majority of respondents felt the stress of home monitoring to be minimal (42.5%) to moderate (37.5%). All respondents favored home monitoring with 80% of parents reporting that the monitor had alerted them to at least one significant apnea or bradycardia episode during the first month of use. Half of parents reported more than five significant alarms in the first month of use. Financial hardship on the family was reported to be minimal. A few parents related significant strain on marital and other sibling-parent relationships. Concerns most commonly voiced were mechanical problems (70%), difficulty in locating qualified and willing babysitters (62.5%), and desire for more concrete information from the physician regarding the child's medical problem (40.0%). These results confirm good acceptance of home monitors by the family and offer direction in dealing with the families' primary concerns. PMID- 4036992 TI - Stimulating effect of fructose 1-6 diphosphate on the phagocytic function of rat RES and on human leukocyte carbohydrate metabolism. AB - The phagocytic behavior of the reticuloendothelial system in the rat was assessed by a quantitative technique following fructose-1,6-diphosphate (FDP) administration. In addition, the effect of FDP on the carbohydrate metabolism of human leukocytes was investigated. The rate of colloidal carbon clearance from the blood was increased significantly in the FDP-treated rats as compared to dextrose and saline controls (p less than 0.001). FDP also attenuated the hepatic decrease of ATP (p less than 0.005) and creatine phosphate (p less than 0.005) that has been observed after intravenous administration of colloidal carbon. Carbohydrate metabolism in human leukocytes was enhanced by FDP, with a concomitant increase in ATP content (p less than 0.001). Experimental evidence suggests that FDP intervenes in the Embden-Meyerhof pathway both as a metabolic regulator and as a high energy substrate. These properties of FDP in stimulating the carbohydrate metabolism have recently been described in man. PMID- 4036994 TI - Repeated first-trimester pregnancy loss: evaluation and management. AB - The clinical management of repetitive first-trimester pregnancy loss is handicapped by inadequate answers to four fundamental questions. These questions center around understanding the true scope of the problem, differentiating between euploidic and aneuploidic loss, identifying the parental source of the gametogenic error, and clarifying the role of molecular developmental mutants in euploidic abortion. In spite of these limitations a diagnostic and therapeutic program is outlined for couples with repetitive early abortion. Informational gaps are identified and the future role of molecular biology in clarifying some of these issues is optimistically outlined. PMID- 4036995 TI - Receiver operating characteristic analysis of glycosylated hemoglobin and the standard test for carbohydrate intolerance in pregnancy. PMID- 4036996 TI - Preeclampsia and fetal heart rate decelerations. PMID- 4036997 TI - The risk of serious complications from induced abortion: do personal characteristics make a difference? AB - We examined the age, gestational age, parity, race, and number of previous spontaneous and induced abortions of 82,030 women who obtained abortions at less than or equal to 24 weeks' gestation. Among these women, 342 (0.4%) had serious complications, including 130 (0.2%) with fever greater than or equal to 38 degrees C for 3 or more days, 172 (0.2%) who required transfusions, 67 (0.1%) who required unintended surgery, and three who died. Factors significantly (p less than 0.05) associated with serious complications varied by period of gestation, including previous induced abortions (adjusted relative risk = 1.57, 95% confidence interval = 1.03 to 2.40) for procedures done at less than or equal to 12 weeks' gestation, advancing age (relative risk for a 5-year increment = 1.12, 95% confidence interval = 1.01 to 1.24), and advancing gestational age (relative risk for a 2-week increment = 1.50, 95% confidence interval = 1.43 to 1.57) for procedures done at greater than 12 weeks, and greater than or equal to 1 previous delivery (relative risk = 1.34, 95% confidence interval = 1.03 to 1.75) for all gestational ages. Although Hispanic women had higher rates of complications compared with white women, data were not available to control for socioeconomic status in comparing race groups. There was no significant association between previous spontaneous abortions and serious complications. Risk patterns were similar, but not identical, when fever, operation, and transfusion were considered separately. PMID- 4036998 TI - Associations between unfavorable outcomes in successive pregnancies. AB - Spontaneous abortions in preceding pregnancies were associated with a significantly increased risk of preterm births (less than 37 weeks) and intrauterine growth retardation in the index pregnancies that followed next, even when the effects of risk factors for the index pregnancy were controlled. The predictive effect of the earlier spontaneous abortion was independent of the effect of the risk factors, even though the latter's effect was over twice as great as indicated by odds ratios. The most serious types of severe intrauterine growth retardation occurred more frequently in high-risk than in low-risk pregnancies. Among mothers whose previous pregnancy resulted in low birth weight, the current pregnancy almost always had one or more risk factors. PMID- 4036999 TI - Effects of hypoxemic events on breathing, body movements, and heart rate variation: a study in growth-retarded human fetuses. AB - In 14 growth-retarded human fetuses, breathing and body movements were studied before, during, and after late heart rate decelerations. Heart rate variation was measured before and after the decelerations. Breathing and body movements were significantly reduced during and after the deceleration. Heart rate variation was reduced after the decelerative episode. Since late heart rate decelerations are presumably signs of acute fetal hypoxemia, there is evidence that these reductions are caused by hypoxemia. The results suggest, furthermore, that just as in fetal sheep, these changes might be mediated by a change in brain activity state. PMID- 4037000 TI - The effect of different human chorionic gonadotropin assay sensitivity on screening for ectopic pregnancy. AB - The distribution of human chorionic gonadotropin levels in 184 patients with ectopic pregnancy is examined. The impact of changing the sensitivity of human chorionic gonadotropin testing on the incidence of false negative results is discussed. Pregnancy blood tests with a detection threshold of 200 mIU/ml were associated with an 11.9% incidence of false negative results. PMID- 4037001 TI - Fetal distress secondary to vancomycin-induced maternal hypotension. PMID- 4037002 TI - Predictive value of roll-over test in women with mild preeclampsia. AB - Fifty women with mild preeclampsia underwent a roll-over test upon admission and again during treatment. The results of the second test showed significant correlation with the severity of the disease and the clinical course until delivery. PMID- 4037003 TI - Serous cystadenocarcinoma as incidental finding during a repeat cesarean section. AB - Primary ovarian carcinoma and pregnancy are rarely found to coexist. We report here a case of cystadenocarcinoma discovered as an incidental finding during an elective cesarean section in a 26-year-old woman. PMID- 4037004 TI - Intrauterine atrial fibrillation associated with fetomaternal hemorrhage. AB - Atrial fibrillation is an arrhythmia that is rarely diagnosed in utero. We report a case of fetal atrial fibrillation documented by antepartum echocardiography associated with a fetomaternal hemorrhage. PMID- 4037005 TI - Dipeptide transport in brush-border membrane vesicles isolated from normal term human placenta. AB - We studied the transport of glycylsarcosine by the brush-border membrane vesicles isolated from normal term human placentas. This dipeptide resisted hydrolysis by placental membrane vesicles and was transported intact into an osmotically responsive intravesicular space. The transport process was Na+-independent and probably occurred down a concentration gradient. Many peptides inhibited the transport of glycylsarcosine whereas amino acids had no effect. These results demonstrate, for the first time, the presence of a dipeptide transport system in the human placenta. PMID- 4037007 TI - Effect of parenteral magnesium sulfate on penicillin-induced seizure foci in anesthetized cats. AB - The use of magnesium sulfate as an anticonvulsant remains controversial. The effect of parenteral magnesium sulfate on established penicillin-induced seizure foci in anesthetized cats was studied. After induction of an epileptic focus by application of penicillin to the cerebral cortex, experimental animals were infused intravenously with magnesium sulfate, whereas control animals received normal saline solution at an equivalent rate. Experimental animals achieved a mean serum magnesium level of 11.73 +/- 2.00 mg/dl. Analysis of the electroencephalogram recordings demonstrated no significant difference in epileptic spike activity between the experimental and control groups. The critical importance of adequate controls in studies of this type is stressed. PMID- 4037006 TI - Content of the collagen and elastin cross-links pyridinoline and the desmosines in the human uterus in various reproductive states. AB - During pregnancy the collagen content of the human uterus increases sevenfold and the elastin content increases fourfold to fivefold. The stable pyridinoline cross link is found in uterine collagen at a level of 0.11 mol per mole of collagen. The same ratio, or a higher one, is found at the end of pregnancy, indicating that pyridinoline synthesis keeps pace with the rapid synthesis of collagen. This cross-link would participate in the maintenance of high mechanical strength of the uterus needed during parturition. Uterine elastin contains 2.4 residues of desmosine plus isodesmosine in 1000 residues of amino acids. This value falls to 0.95 at term, indicating that synthesis of desmosines does not keep pace with the synthesis of elastin. Therefore, desmosine measurements do not provide an accurate index of elastin changes in pregnancy. Collagen and elastin contents in nongravid uteri increase with successive pregnancies; the cross-links remain constant during this change. PMID- 4037008 TI - Autologous antibodies eluted from membrane fragments isolated from the effusions of human ovarian epithelial neoplasms. I. Quantitation of antibodies. AB - Cyst and ascites fluids from patients with ovarian epithelial neoplasms contain large amounts of soluble immunoglobulins without detectable antibody activity against human ovarian tumor cell lines by indirect immunofluorescence. Membrane fragments were prepared from 56 human ovarian effusions, and the presence of membrane-bound IgG, IgA, and IgM was demonstrated. The predominant membrane-bound immunoglobulin class was IgG, which ranged from 18 to 4275 ng/ml on samples tested, whereas IgA was present in the range of 5 to 52 ng/ml. The autologous membrane-bound antibodies strongly recognized cell-surface antigens on four human ovarian cell lines and four surgical specimens of human ovarian adenocarcinoma but did not react with normal human ovaries, non-ovarian normal and neoplastic tissues, or non-ovarian human cell lines by indirect immunofluorescence assay. These studies indicate that patients with ovarian cancer have the capability of recognizing and forming antibodies against autologous ovarian tumor-associated antigens. PMID- 4037009 TI - Preterm rupture of the membranes: combination therapy. AB - Preterm rupture of the membranes poses perhaps the greatest threat to perinatal survival. Unfortunately, the literature leaves us in a quandry as to the management of the problem. At the Medical University of South Carolina for the past 3 years, aspects of both active and passive management have been used. Vaginal pool phospholipid analysis, the use of corticosteroids whenever appropriate, and tocolysis (in an attempt to gain 48 hours) were used in 96 consecutive patients with premature rupture of the membranes between 26 and 36 weeks' gestation. Decisions about delivery were dictated by spontaneous onset of labor and/or evidence of chorioamnionitis. This regimen prolonged gestation an average of 4.6 days. Maternal and neonatal infectious morbidity was uncommon. Clinical chorioamnionitis was diagnosed in 5.2% of mothers, and only 8.5% of all neonates had evidence of serious infection. Respiratory distress syndrome was seen in 12.8% of neonates. There were only three perinatal deaths, and most babies (92.5%) were discharged without residual problems (average hospital stay, 18.1 days). A detailed analysis of the group by gestational age categories will be presented. PMID- 4037010 TI - Report of a successful delivery after nonsurgical management of a choriocarcinoma related pelvic arteriovenous fistula. AB - A case of a pelvic arteriovenous fistula is described 5 years after treatment of trophoblastic disease. Hypogastric embolization, rather than an operation, was used to obliterate the fistula. Pregnancy occurred 1 year later and a healthy infant was delivered. This is the first report of a delivery after angiographic management alone. PMID- 4037011 TI - Management of stage IA carcinoma of the cervix. AB - One hundred fourteen patients with Stage IA carcinoma of the cervix were retrospectively reviewed in regard to depth of invasion, capillary-like space involvement, stromal reaction, status of conization margins, and the incidence of lymph node metastasis. Type of treatment, recurrences, and deaths were also evaluated. Patients with less than 3 mm invasion can be treated conservatively, including conization, if fertility is desired. No lymph node metastasis or recurrence appeared in this group of patients irrespective of type of treatment. Patients with 3 to 5 mm invasion do appear to be at higher risk for recurrence, but conservative therapy may be used in individualized situations. Size of conization and status of surgical margins appear to be important determining factors in regard to conservative therapy. Data in the literature, as well as our experience, although limited, suggest that the status of capillary-like space involvement does not influence lymph node metastasis or recurrence. Invasion of 5 mm or more in depth should be treated as a Stage IB occult lesion. PMID- 4037012 TI - Systemic lupus erythematosus and reproductive function: a case-control study. AB - Systemic lupus erythematosus characteristically afflicts women of reproductive age, yet the explanation for this feature is unknown. This hospital-based, case control study of 109 incident cases of systemic lupus erythematosus and 109 randomly selected controls was conducted to search for risk factors related to reproduction. Women who were 34 years of age and younger had a crude risk of systemic lupus erythematosus 3.6 times that of older women, and women who were of minority races had a crude risk 4.8 times that of white women (P less than 0.001). Prior hysterectomy or tubal sterilization had a significant protective effect (odds ratio, 0.55; 95% confidence interval, 0.31 to 0.99). Endometriosis was associated with a twofold increased risk of systemic lupus erythematosus, although this was not statistically significant. The latter two findings are consistent with the hypothesis that retrograde menstruation may be an inciting factor for systemic lupus erythematosus in susceptible women. PMID- 4037013 TI - Intraperitoneal chromic phosphate P 32 suspension therapy of malignant peritoneal cytology in endometrial carcinoma. AB - Malignant peritoneal cytology in patients with endometrial carcinoma is a poor prognostic feature, identifying patients at high risk for early intra-abdominal recurrence. Between 1977 and January, 1983, 65 women with endometrial carcinoma who had malignant peritoneal cytology were treated with adjuvant intraperitoneal radioactive chromic phosphate P 32 suspension. Fifty-three patients (80%) were clinical Stage I, nine (14%) were Stage II, and three (7%) were clinical Stage III. Life-table estimates of disease-free survival were 89% for clinical Stage I patients and 94% for surgical Stage I patients beyond 24 months. One patient developed an intraperitoneal recurrence, four had simultaneous intraperitoneal and extraperitoneal recurrences, and six developed recurrences outside of the peritoneal cavity. Few significant acute complications occurred after therapy with radioactive chromic phosphate P 32 suspension. Chronic intestinal morbidity that required surgical correction was encountered in five of 17 patients (29%) who received adjuvant pelvic radiation, compared to none of the 48 patients (0%) who received only radioactive chromic phosphate P 32 suspension (p less than 0.001). Intraperitoneal instillation of radioactive chromic phosphate P 32 suspension is effective therapy for patients with malignant peritoneal cytology from endometrial carcinoma. Caution should be exercised when radioactive chromic phosphate P 32 suspension and external radiation therapy are combined. PMID- 4037014 TI - Homologous insemination--revisited. AB - Between July 1, 1969, and December 31, 1983, 1774 patients were evaluated in the private infertility clinic at the University of Virginia Hospital. Homologous artificial insemination was performed in 158 patients for the following indications: male factor (75.3%), cervical factor (16.7%), sperm deposition problem (3.7%), patient's request (2.5%), and immunologic factor (1.8%). Whole ejaculate insemination was performed in 68 patients; split ejaculates were used in 90 women. Additional fertility factors in 140 patients included endometriosis, anatomic abnormalities, and ovulatory difficulties. Of the 158 women, 23 (14.6%) had a total of 27 pregnancies (mean number of cycles, 5.7); 135 failed to conceive during treatment with homologous artificial insemination (mean number of cycles, 8.4). Most pregnancies (70.4%) occurred in those patients in whom homologous artificial insemination was used for a male factor. Among the 135 couples who failed to conceive with homologous artificial insemination, 20 (14.8%) patients subsequently had 25 pregnancies. Male factor had been the indication for homologous artificial insemination in 72% of the couples. Pregnancy outcomes were similar in all subgroups. Homologous artificial insemination may not be indicated for male factor-related infertility. PMID- 4037015 TI - Pregnant women with Munchausen syndrome. AB - Munchausen syndrome is relatively common in pregnant women. Ten cases are presented. The symptoms may be anything that will achieve hospital admission. Our experience suggests that the patients be allowed to consider themselves ill so that escalation of their illness can be avoided. PMID- 4037016 TI - Biologic and morphologic development of donated human ova recovered by nonsurgical uterine lavage. AB - Using uterine lavage performed 5 days after the luteinizing hormone peak, we collected 25 uterine ova from five fertile donors who had had a single, periovular artificial insemination. After examination, all recovered ova were transferred to recipient uteri and resulted in three intrauterine and one tubal pregnancy. Morphologic development ranged from degenerating single-cell ova to mature blastocysts. Ages of the ova at recovery ranged from 93.5 to 130.0 hours postovulation. Mean age of the five blastocysts, 109.1 hours, was not significantly different from the mean age of the 20 less mature ova, 108.1 hours. Neither the mean interval from insemination to recovery for blastocysts nor the mean interval from insemination to ovulation for blastocysts was significantly different from the mean intervals of the other ova. The five blastocysts resulted in intrauterine pregnancies in three recipients. There were no intrauterine pregnancies from the other 20 transfers (p less than 0.004). A transferred 12 cell ovum with degenerating blastomeres was associated with tubal pregnancy in the recipient. The large variability in the state of intrauterine ova observed in the relatively fixed postovulatory interval of this study appears to be due to differences in viability and maturation, not differences in ovum age. Maturational state of the ova at the time of transfer appears to be a significant determinant of the likelihood of ensuring pregnancy. PMID- 4037017 TI - Prolactin bioactivity following decidual synthesis and transport by amniochorion. AB - Current evidence suggests that high concentrations of prolactin in human amniotic fluid result from the transport of human decidual prolactin across reflected amniochorion. In this study, tritiated leucine placed on the isolated maternal side of amniochorion with adherent decidua was incorporated into newly synthesized tritiated human decidual prolactin. Identification of tritiated decidual prolactin on the fetal side of suspended membranes was confirmed within 4 hours of incubation. A heterologous species of human decidual prolactin identified on the maternal side of membranes was also detectable on the fetal side, and its bioactivity was found to be equivalent in both fetal and maternal chambers separated by amniochorion. These results confirm the de novo synthesis of human decidual prolactin and transport by amniochorion to the fetal side. Subsequent to transport, the biologic activity of human decidual prolactin is retained. Thus concentrations and biologic activity of amniotic-fluid prolactin can be accounted for by the transport of newly synthesized human decidual prolactin by the reflected amniochorion. PMID- 4037018 TI - Delayed hemolytic transfusion reaction: a cause of late postoperative fever. AB - Delayed hemolytic transfusion reaction, an uncommon complication of blood transfusion, can be the cause of late postoperative fever in the gynecologic patient. The triad of fever, anemia, and a history of recent blood transfusion is the hallmark of this diagnosis. PMID- 4037019 TI - Short-term tocolysis adjunctive to intrapartum term breech management. PMID- 4037020 TI - Do midforceps deliveries really impair subsequent intelligence quotient scores? PMID- 4037021 TI - Placentas of small-for-dates infants from Mexico City, Mexico. PMID- 4037022 TI - Effect of cataract surgery on intraocular pressure reduction obtained with laser trabeculoplasty. AB - Thirty-nine eyes of 34 patients with open-angle glaucoma who had been treated successfully with argon laser trabeculoplasty underwent either extracapsular cataract extraction with posterior chamber intraocular lens implantation or intracapsular cataract extraction without lens implantation. Cataract surgery did not have a significant effect on the magnitude of intraocular pressure reduction obtained with laser trabeculoplasty. This study supports the view that eyes with coexisting cataract and glaucoma may benefit from laser trabeculoplasty before cataract surgery. PMID- 4037023 TI - Comparison of the effects of Viscoat and Healon on postoperative intraocular pressure. AB - We compared the effects of Viscoat and Healon on postoperative increases in intraocular pressure in patients undergoing uncomplicated extracapsular cataract extraction with posterior chamber intraocular lens implantation in a prospective, randomized, single-masked study. Eleven eyes received Viscoat and 13 received Healon. The Viscoat or Healon was aspirated from the anterior chamber with the irrigation-aspiration tip of an automated irrigation-aspiration system at the end of the procedure. No prophylactic intraoperative or postoperative ocular hypotensive agents were used. Intraocular pressure was measured at three, six, 12, and 24 hours postoperatively. Compared with preoperative intraocular pressure, postoperative intraocular pressure was significantly increased in both the Viscoat group and the Healon group. Some postoperative intraocular pressures were as high as 50 to 60 mm Hg, despite removal of the viscoelastic substance at the end of surgery. There was no significant difference in the postoperative intraocular pressures of the Viscoat group and the Healon group. PMID- 4037024 TI - Pigmentary glaucoma associated with posterior chamber intraocular lenses. AB - Six cases of glaucoma associated with pigment dispersion syndrome occurred after the implantation of posterior chamber intraocular lenses. All six patients had iris transillumination defects associated with the intraocular lens haptics, increased intraocular pressure, and pigment deposition in the trabecular meshwork and the anterior chamber. Medication controlled the glaucoma and none of the patients required further surgery. PMID- 4037025 TI - Diagnosis and management of Acanthamoeba keratitis. AB - Diagnosis and management of Acanthamoeba chronic ulcerative keratitis is difficult. Two cases of Acanthamoeba keratitis at Wills Eye Hospital were diagnosed within several months of each other during 1983. Corneal transplantation was necessary for diagnosis and therapy in these cases. Another two cases were diagnosed when histopathologic specimens from penetrating keratoplasties done between 1974 and 1983 were reviewed retrospectively. There has been no evidence of recurrent disease in any of our cases during follow-up periods averaging two years (range, 12 to 40 months). The diagnosis of Acanthamoeba keratitis must be considered in cases of chronic progressive corneal ulceration unresponsive to medical therapy. PMID- 4037026 TI - Mycotic endophthalmitis caused by Penicillium sp. after parenteral drug abuse. AB - A 30-year-old man developed endophthalmitis three weeks after an intravenous injection of hydromorphone hydrochloride. Penicillium species was recovered from a vitreous aspirate. Treatment with amphotericin B and flucytosine resulted in documented sterilization of the vitreous. At a six-month follow-up examination, the visual acuity of the involved eye was still limited to light perception. PMID- 4037027 TI - Ocular findings in leprosy in the United States. AB - We examined 55 clinic patients with biopsy-proven Hansen's disease and catalogued the ocular findings. Forty patients had lepromatous disease and 15 had tuberculoid disease. Visual acuity was 20/40 or better in 52 patients. Examination of pupillary size in all cases and after dilation with cocaine and hydroxyamphetamine in 15 cases showed decreased sympathetic innervation to the iris dilator muscle in seven cases. Ocular inflammation was uncommon: there was one case of active interstitial keratitis, three of episcleritis, and four of iritis. Although 41 patients had ocular problems attributable to Hansen's disease, the severity of the ocular complications was much less than reported in similar studies from other countries. We believe that the differences were the result of effective antimicrobial and anti-inflammatory therapy. PMID- 4037028 TI - The correlation between optic disk topography measured by the video ophthalmograph (Rodenstock analyzer) and clinical measurement. AB - The video-ophthalmograph (Rodenstock analyzer) records the topography of the optic disk via simultaneous stereoscopic images, which are stored and analyzed with the help of a microcomputer. We performed a prospective study on 68 eyes of 68 patients to compare the vertical cup-disk ratio obtained with the video ophthalmograph to that obtained with manual analysis of black-and-white stereoscopic photographs. The correlation coefficient was 0.61, highly significant at P = .0000. PMID- 4037029 TI - Automated differential threshold perimetry for detecting glaucomatous visual field loss. AB - Because early glaucomatous visual field defects occur asymmetrically across the horizontal meridian, we analyzed data from automated perimetry by comparing sums of threshold values of corresponding groups of points in the superior and inferior hemispheres of the central 30 degrees tested by the Humphrey Field Analyzer. We developed patterns and criteria from 25 early glaucomatous and 36 normal control eyes to achieve optimal balance between sensitivity (96%) and specificity (86%). Application of these criteria to an independent group of 27 glaucomatous and 105 control eyes yielded a sensitivity of 88.9% and specificity of 85.7%. Minor modification of the criteria improved sensitivity and specificity to more than 90% for both patients and controls. PMID- 4037030 TI - Idiopathic inflammatory perioptic neuritis simulating optic nerve sheath meningioma. AB - Between 1976 and 1982, we examined 13 patients with clinical and radiographic findings consistent with optic nerve sheath meningioma. All patients had visual loss, evidence of optic nerve dysfunction, centrocecal visual field defects, and echographic and computed tomographic evidence of optic nerve or sheath enlargement. All underwent surgery for biopsy or excision of their presumed tumors. However, adequate histologic sampling of all lesions failed to demonstrate meningioma in four patients; two of these four showed inflammatory infiltration of the dural sheath, whereas the other two showed only edematous or dense fibrous tissue. There was no evidence of other systemic disease in any of these cases. We conclude that optic nerve or sheath enlargement, probably induced by an idiopathic inflammatory perioptic neuritis, may simulate a sheath meningioma. Proper diagnosis requires biopsy confirmation. PMID- 4037031 TI - Anemia and diabetic retinopathy. AB - Three patients (a 44-year-old woman, a 65-year-old man, and a 39-year-old woman) who had had diabetes mellitus for an average of 17 years had good vision and mild to moderate background diabetic retinopathy. These patients developed severe iron deficiency anemia from varying causes and their conditions rapidly progressed to a severe proliferative phase that necessitated panretinal photocoagulation and pars plana vitrectomy in two cases. PMID- 4037032 TI - Juvenile iridoschisis and microphthalmos. AB - Spontaneous iridoschisis and corneal edema developed in the microphthalmic eye of an 8-year-old. There was no history of trauma, inflammation, or congenital iris abnormality. PMID- 4037033 TI - Anterior retinal cryotherapy in diabetic vitreous hemorrhage. AB - Recurrent vitreous hemorrhage associated with proliferative retinopathy can occur in eyes that do not satisfactorily respond to argon laser pantretinal photocoagulation. To evaluate the effect of relatively low-risk surgical intervention, we performed peripheral retinal cryopexy on 24 eyes of 23 diabetic patients with proliferative diabetic retinopathy and vitreous hemorrhage. In most cases, cryopexy followed complete or nearly complete panretinal photocoagulation which did not prevent subsequent vitreous hemorrhage. Existing vitreous hemorrhage cleared postoperatively in 23 of 24 eyes. The best corrected visual acuity improved in 15 eyes, remained unchanged in five, and worsened in four. Four postoperative anterior segment complications resolved completely within a short time. One patient, a 68-year-old woman who had had diabetes for 18 years, postoperatively had a macular hole in one eye and macular edema with tractional retinal detachment in the other. PMID- 4037034 TI - The effect of a once-daily oral dose of nadolol on intraocular pressure in normal volunteers. AB - We compared the effects of once-daily oral administration of 20 mg and 40 mg of nadolol vs placebo in 40 normal volunteers in a randomized, double-masked trial. Each of 23 women and 17 men (ranging in age from 18 to 50 years) had intraocular pressure, pulse rate, blood pressure, pupil size, amplitude of accommodation, and near point measured immediately before treatment and then at 24 hours, day 8, and day 15 after treatment. Both dosages of nadolol produced significant decreases in intraocular pressure at three hours (P less than .001). Although both dosages decreased intraocular pressure at 24 hours compared with placebo, only the change with the 40-mg dose was significant (P less than .05). Although both dosages produced significant decreases in pulse rate and blood pressure, side effects were minimal. PMID- 4037036 TI - Gaze palsy associated with viral syndrome. AB - Four cases of gaze paresis occurred in association with viral disease. In three cases the viral prodrome preceded the oculomotor disturbance. In one, gaze palsy was followed several days later by a viral syndrome. One had isolated bilateral horizontal ophthalmoplegia; another patient had motility disturbance with blepharoptosis and peripheral areflexia. Two patients had clinical evidence of brain-stem involvement: unilateral gaze paresis and gaze-evoked nystagmus in one and Parinaud's syndrome in the other. No accompanying long-tract signs or changes in mental status were present in any case. Recovery was complete in all four patients. PMID- 4037035 TI - An investigation into the association between liver damage and metastatic uveal melanoma. AB - We examined the effect of liver damage induced by carbon tetrachloride on the incidence of hepatic metastasis in the Greene hamster melanoma. Nine of 17 animals with liver damage had melanoma growth in the liver after the intraportal vein injection of tumor cells, whereas tumor growth occurred in four of 27 control animals (P less than .01). These results suggest that, in this model, liver damage predisposes to metastatic involvement by melanoma. PMID- 4037037 TI - Fire risks with ophthalmic ointments. PMID- 4037038 TI - Aplastic anemia simulating central retinal vein occlusion. PMID- 4037039 TI - Procoagulant effects of intraocular sodium hyaluronate. PMID- 4037040 TI - Inversion of anterior chamber pigment as a possible prognostic sign in narrow angles. PMID- 4037041 TI - Conjunctival inclusion cyst simulating malignant melanoma. PMID- 4037042 TI - A new corneal protector for oculoplastic surgery. PMID- 4037043 TI - Eyelid ecchymosis and proptosis in lymphangioma. PMID- 4037044 TI - Intraocular ampicillin in the treatment of endophthalmitis. PMID- 4037045 TI - Tear of the retinal pigment epithelium and serous retinal detachment. PMID- 4037046 TI - Digoxin in the subretinal spaces of humans with rhegmatogenous retinal detachments. PMID- 4037047 TI - Effects of topical betaxolol, timolol, and placebo on pulmonary function in asthmatic bronchitis. PMID- 4037048 TI - Eleanor Clarke Slagle lecture, 1985: a monistic or a pluralistic approach to professional identity? AB - Occupational therapists have long been concerned with the process of articulating their identity. This paper describes in detail two approaches to that process: monistic and pluralistic. It demonstrates the advantages of a pluralistic professional identity. PMID- 4037049 TI - Occupational therapy's domain of concern: reconsidered. AB - This paper focuses on the domain of concern part of a professional model presented by Mosey in her book Occupational Therapy: Configuration of a Profession (Raven, 1981). Based on additional review of the literature, I suggest two principal alterations. A change in core versus parameter. "Human occupation" replaces "occupational performance" and is presented as the core of the domain of concern because this is the focus of occupational therapy practice; the "performance components" defined here as "competence components" actually serve as a parameter of practice. A reconceptualization of two parameters: "time" and "cultural environment." Time should be considered a separate parameter, including categories of time practice, balance of activities over time, and time perspective. Cultural environment is perceived as a parameter that is composed of four categories: the symbolic, social, physical, and natural environments. This paper emphasizes the interrelatedness of all parts of the model and points out the qualitative differences between the parameters. PMID- 4037050 TI - Performance of female adults on the Southern California Visual Figure-Ground Perception Test. AB - This study was conducted to assess adult female performance on the Southern California Visual Figure-Ground Perception Test (FGP) and to obtain an estimate of the test's reliability. Data were obtained for two scoring formats. The first format was the score for all items on the test (TOTAL), and the second format was the score through the fifth error (FIRST-FIVE). The mean scores were 38.24 (SD = 3.2) for TOTAL and 29.71 (SD = 10.14) for FIRST-FIVE. For each format, mean, standard deviation, kurtosis, and skewness values are presented (N = 124). Both formats were reliable over time (.90 and .71, respectively), and scores of the even-numbered items correlated moderately with the odd-numbered items, indicating split-half reliability (.70 and .87 for both administrations of the test). Although the sample was representative across the socioeconomic variable, moderate correlations were obtained between the performance scores and the age and education level variables. We concluded that the FGP is a reliable assessment tool for use with adults; however, a subject's age and education must be considered when interpreting the scores. PMID- 4037052 TI - A distal support sling for the hemiplegic patient. PMID- 4037051 TI - Pinch and grasp strength: standardization of terminology and protocol. AB - We implemented a tridirectional survey to begin the standardization process for grasp and pinch terminology and protocols for testing and to improve the communication between rehabilitation professionals who assess hand strength. We surveyed the literature, occupational therapy clinics across the country, and occupational therapy educational programs. Our results reveal the current use, teachings, and recommendations of pinch and grasp strength measurement. The results confirm that the standardization of grasp and pinch terminology and protocols for testing are vitally needed. Specific recommendations to continue this standardization process are recommended. PMID- 4037053 TI - Implications for occupational therapy of a competency-based orientation. PMID- 4037054 TI - The effects of wearing the Boston II gas-permeable contact lens on central corneal curvature. AB - Keratometric readings on 132 different eyes were examined from the patient records. Sixty eyes had previously worn polymethyl methacrylate (PMMA) lenses and then were refitted with the Boston II gas-permeable contact lens. The remaining 72 eyes had never worn contact lenses and these too were fitted with the Boston II lens. The Boston II contact lens is a nonhydrophilic contact lens composed of methylmethacrylate-dimethylitaconate-siloxanyl copolymer with a reported Dk value of 14.6 X 10(-11) ml O2 cm2/s ml mm Hg (35 degrees C). The mean and SD of the keratometric readings and the amount of corneal toricity found were calculated for each set of progress reports. The data in this study indicate that an alignment-fitting Boston II gas-permeable contact lens does not cause curvature changes in corneas during the first three months of wear. PMID- 4037055 TI - Differences in the perceptual skills development of young myopes and hyperopes. AB - The purpose of this study was to compare the visual perceptual skills of young myopes and hyperopes. The case records of over 700 young University of Houston College of Optometry clinic patients revealed significant differences between the two groups (p less than 0.001), suggesting that myopes are, indeed, more analytical than hyperopes. Comparisons are also made with emmetropes. Implications of these data are discussed. PMID- 4037056 TI - Stereoscopic threshold in children and adults. AB - The threshold of stereoacuity is reported as measured on 369 normal children aged 3 to 7 years, and on 51 normal adults. Four standard clinical stereotests were used and two different testing procedures adopted. The results show that both threshold and variability decrease with age, and performance becomes adult-like at different ages for different tests. Interest correlations are poor, and in cases where the correlation is significant, no identifiable pattern emerges between testing procedures, age, and stereotests. The procedures themselves gave no significant difference in stereoacuity values between all four tests. PMID- 4037057 TI - Single-subject research designs for optometry. AB - Single-subject research designs are used extensively in the fields of education and psychology. There are many advantages of these designs over traditional group designs and they appear particularly important for applied research in optometry. An overview of the basic designs is presented. For each type of design, examples are provided that illustrate the application of this methodology to applied optometric research. PMID- 4037058 TI - Ultrasound measures of vitreous chamber depth during ocular accommodation. AB - The vitreous chamber decreased in depth about 0.12 mm as accommodative demand increased from 0.2 to 7 D in nine accommodative steps. The depth decreases matched movement of the posterior lens surface toward the retina. Accommodation caused no significant increases in axial length compared to cyclopleged controls. These results do not favor the active role for the vitreous in accommodation proposed by Coleman in 1970. Computer analysis of A-scan interval counts demonstrated that multiple retinal complex peaks might erroneously point to vitreous or axial lengthening. About 30% of total lens thickening during accommodation was accounted for by posterior lens surface displacement. PMID- 4037059 TI - Does performance of tasks affect the resting focus of accommodation? AB - Measurements of the resting focus of accommodation were obtained with an infrared optometer while subjects engaged in four tasks: (1) passive viewing in darkness; (2) passive viewing of a laser speckle pattern; (3) active judgment of motion in a laser speckle pattern; and (4) mental arithmetic in darkness. The results showed resting focus measures to be comparable under all four conditions for some subjects. However, other subjects exhibited consistent increases or decreases in the resting focus position when asked to judge the direction of speckles within the laser test pattern or perform mental arithmetic. This finding suggests that "effort to see" may influence the resting focus of some subjects. Implications for measurement procedures and population estimates of the resting focus are discussed. PMID- 4037060 TI - Modeling the electrophysiology of the corneal epithelium and its response to cellular injury. AB - A two-membrane equivalent electrical model was applied to the rabbit corneal epithelium. Single parameters were varied (with the other parameters kept constant) to generate equations predicting the electrical behavior of the corneal epithelium. Due to electrical feedback through the epithelial shunt, each transmembrane voltage is not solely a function of its own membrane parameters. The equations were evaluated with published data and the model successfully approximated the known electrical characteristics of the rabbit corneal epithelium. The principal site of voltage variation in the corneal epithelium is inferred from the slopes calculated from voltage scattergrams. Reduced shunt resistance results from injury to the corneal epithelium in vitro, or from hard contact lens wear in vivo. PMID- 4037061 TI - Peripheral visual field is radially organized. AB - The visibility of vertical, horizontal, and 45 degrees oblique square wave gratings was measured at 10 to 45 degrees of eccentricity along the vertical, horizontal, and the 45 degrees oblique meridians. A forced-choice orientation identification response to the stimulus grating and a subjective rating of the confidence in response accuracy were the response measurements. The best seen grating orientation was always the one parallel to the meridian upon which it was presented. Along the vertical and horizontal meridians the most poorly seen orientation was the one perpendicular to the meridian. Along the 45 degrees oblique meridians the horizontal grating was as poorly seen as the meridian perpendicular to the grating orientation, except in the infranasal quadrant of the field. Pinhole experiments show these results unlikely to be due to off-axis optical aberrations. It is hypothesized that the radial organization of the peripheral visual field is due to underlying neural factors ontogenically determined, not due to environmental adaptations. PMID- 4037062 TI - Vergence adaptation maintains heterophoria in normal binocular vision. AB - This investigation sought to determine whether vergence adaptation serves to maintain orthophoria or heterophoria in normal binocular vision. While wearing prisms which neutralized their nearpoint (40 cm) heterophorias, 27 of 30 nonstrabismic subjects adapted from their prismatically created orthophoria toward their habitual heterophoria. Three subjects showed no adaptive response. A symptom questionnaire distributed to these subjects determined that the maintenance of heterophoria by vergence adaptation is: characteristic of normal and comfortable binocular vision, and neither an entirely necessary nor sufficient condition for normal and comfortable binocular vision. PMID- 4037063 TI - Comparison of refractive findings obtained by the Bausch and Lomb IVEX and by conventional clinical refraction. AB - The Bausch and Lomb IVEX (Integrated Vision Examination System) is a computerized refractor, designed for both subjective and objective refraction and binocular vision testing. Using a double-masked protocol, subjective refraction findings were obtained on 40 subjects by means of both IVEX and conventional clinical refraction. Although for most subjects IVEX spherical equivalent findings varied by no more than 0.25 or 0.50 D from conventional refractive findings, for some subjects IVEX findings yielded more minus or less plus than conventional refractive findings by as much as 1.00 or 1.25 D. PMID- 4037064 TI - Heparin-binding fragments of fibronectin are potent inhibitors of endothelial cell growth. AB - Two heparin-binding proteolytic fragments of fibronectin--an amino-terminal 29-kd segment and a carboxyl-terminal 40-kd segment-are apparently specific, potent inhibitors of the growth of cultured bovine aortic endothelial cells and inhibit growth in a reversible, dose-dependent manner. In contrast, native fibronectin at higher dosages neither inhibits nor interferes with the effects of the 29-kd fragment. The data, therefore, suggest that fibronectin fragments may participate in the regulation of vascular growth. PMID- 4037065 TI - Ultrastructure of the attack of eosinophils stimulated by blood mononuclear cell products on schistosomula of Schistosoma mansoni. AB - Purified human eosinophils were treated with peripheral blood mononuclear cell supernatants containing eosinophil cytotoxic enhancing activity (ECEA). Schistosomula of Schistosoma mansoni which had been coated either with antibody (Ab) from the sera of infected patients or with the lectin concanavalin A (Con A) were incubated with ECEA-treated and untreated cells for 2 minutes to 12 hours and examined ultrastructurally. Killing was assayed at 18 hours. ECEA caused an increase in the killing of Ab-coated worms, but Con-A-coated worms were not killed by either ECEA-treated or untreated cells. Eosinophils began to degranulate on Ab-coated worms within 2 minutes and continued to degranulate, so that by 12 hours about half of the parasites had greater than 50% of their surface covered by discharge material. The ECEA-treated cells degranulated more than the untreated cells. There was much less discharge material on Con-A-coated worms than on Ab-coated worms. Eosinophils adhered to discharge material on the surface of both Ab- and Con-A-coated parasites. At 3 and 12 hours, lysed cells and cell fragments were also seen adhering to discharge material. In the absence of discharge material the cells adhered to residual glycocalyx or to the tegumental outer membrane. These studies suggest that eosinophils kill schistosomula by progressively degranulating onto their surface over many hours and that the increased toxicity caused by ECEA is due to an increase in discharge. PMID- 4037067 TI - Hepatitis B virus DNA detected in formalin-fixed liver specimens and its relation to serologic markers and histopathologic features in chronic liver disease. AB - To examine the relationship of hepatitis B virus (HBV) DNA sequences in the liver with histopathologic features and antigenic markers, the authors determined the hepatocytic status of viral DNA by in situ hybridization in formalin-fixed liver sections using a biotinylated probe in 45 patients with various chronic liver diseases. The results were compared retrospectively with the HBV serologic markers and histopathologic features including the presence of ground-glass cells or Shikata staining positivity. The specificity of this in situ detection of HBV DNA has been proven excellent in a double-blind control study in 18 patients in whom liver HBV DNA was also determined by DNA extraction, gel electrophoresis, and the Southern blotting technique. In 41 patients, the findings of HBV DNA and serologic markers were concordant (17 positive and 24 negative). Twelve of the 20 HBV-DNA-positive patients were HBsAg-positive (6 with chronic hepatitis, 3 with cirrhosis, and 3 with hepatocellular carcinoma). Ground-glass cells or Shikata positivity were found in 10 of these 12 patients. HBV DNA sequences were found in the liver of all patients with chronic liver disease and serologic positivity for HBV infection. In liver with normal histologic features, HBV DNA was not demonstrable, despite the positive anti-HBc and anti-HBs. However, a positive HBV DNA was found in 3 serologically negative patients. In another patient the interpretation of findings was impossible because of severe hemosiderosis. From this study, it is concluded that in situ detection of HBV DNA in formalin-fixed liver sections has a clinical value and is suitable for routine use. PMID- 4037066 TI - Evolution of foam cells in subcutaneous rabbit carrageenan granulomas. II. Tissue and macrophage lipid composition. AB - This study describes the lipid composition of differentiating macrophage-derived foam cells in the inflammatory carrageenan granuloma. In this model, macrophages exposed in vivo to diet-induced hypercholesterolemia progressively accumulate electron-translucent lipid inclusions; and at 14 and 28 days, many assume the morphologic features of arterial plaque foam cells. Subcutaneous carrageenan granulomas were induced in 24 pellet-fed (NC) and 24 cholesterol-fed (HC) rabbits, and tissue was harvested at 4, 14, and 28 days. Total (TC) and free cholesterol (FC), cholesteryl esters (CEs), CE fatty acids, triglycerides (TGs), and phospholipids (PLs) were measured on lipid extracts from tissue. TC, FC, and CEs were also measured on isolated, cultured granuloma macrophages. Tissue TCs and FCs were significantly elevated in HC relative to NC rabbits at both 14 and 28 days (P less than 0.005 and P less than 0.01, respectively). CE accumulation in HC granuloma tissue was 80-fold greater at 14 days and 178-fold greater at 28 days (P less than 0.005), compared with NC granulomas. Oleic acid (18:1), the principal CE fatty acid in both NC and HC granulomas, accounted for significantly more (P less than 0.05) of the total CE fatty acids in HC (48%) relative to NC granulomas (37%). No net accumulation of TG was observed with time in NC or HC animals. Although diet did not influence tissue PL content, significant increases (P less than 0.05) were observed at 14 days in NC rabbits and at 14 and 28 days in HC rabbits relative to 4-day levels. CE accumulation was significantly greater in cultured macrophages isolated from HC granulomas at 14 days (P less than 0.001) and 28 days (P less than 0.01). These findings have demonstrated the significant accumulation of CEs in both HC granuloma tissue and in cultured HC macrophage/foam cells in vivo. The carrageenan granuloma model has, we believe, considerable potential for defining mechanisms responsible for CE accumulation in the differentiating macrophage-derived foam cell. PMID- 4037068 TI - Heparin and glomerular epithelial cell-secreted heparin-like species inhibit mesangial-cell proliferation. AB - The regulation of cell growth in the kidney glomerulus plays a key role in many physiologic and pathologic processes. In this communication, the authors examine the possible role of heparin-like species as inhibitors of mesangial-cell proliferation. Heparin profoundly inhibited the growth of cultured mesangial cells in a dose-dependent manner, with an ED50 = 5-10 micrograms/ml. The antiproliferative activity of heparin was reversible and specific for mesangial cells as the target cell in the glomerulus. Heparin was much more effective than other glycosaminoglycans. Cultured glomerular epithelial cells were found to secrete both stimulators and inhibitors of mesangial-cell growth. Approximately half of the inhibitory activity was destroyed by a highly purified heparinase; the other half was sensitive to trypsin. Approximately 80% of the mitogenic activity was protease-sensitive. These results suggest that heparin and glomerular epithelial cells may participate in mesangial-cell growth regulation. PMID- 4037069 TI - Animal model of human disease. Avian scleroderma. An inherited fibrotic disease of white Leghorn chickens resembling progressive systemic sclerosis. PMID- 4037070 TI - Passive sodium and potassium movements in sickle erythrocytes. AB - Deoxygenation causes an increase in passive Na and K movements across the membrane of the sickle erythrocyte. Some investigators find that these ion movements are accompanied by cell dehydration, while others find no evidence for cell water loss with sickling. Because gelation of hemoglobin S would be enhanced by cell water loss, we reinvestigated Na and K movements in sickle cells to define further the role that ion movements might play in the pathogenesis of sickling. With deoxygenation, we found that sickle cells gained Na and lost K without losing cell water. These net ion movements were not seen in control red blood cells. For sickle cells, deoxygenation also increased passive unidirectional influxes of Na and K, effects not observed when control red blood cells were deoxygenated. The deoxygenation-induced passive influxes of Na and K in sickle cells were not diminished by anion substitution or by the addition of the diuretic furosemide. We also found differences in passive Na and K fluxes between oxygenated sickle cells and normal red blood cells. The addition of furosemide or replacement of Cl with NO3 or SCN, maneuvers that largely reduced passive Na and K movements in oxygenated normal cells, had no effect on Na and K movements in oxygenated sickle cells. These findings militate against the idea that solute and water loss occur as a consequence of deoxygenation but do indicate that there are acquired membrane abnormalities in sickle red blood cells. PMID- 4037071 TI - Myosin phosphorylation, force, and maximal shortening velocity in neurally stimulated tracheal smooth muscle. AB - Field stimulation of intrinsic nerves in bovine tracheal smooth muscle strips elicited atropine-sensitive contractions that were more rapid than those obtained by addition of carbamylcholine to the bathing medium. These stimulus conditions were used to improve estimates of maximal rates of activation as indicated by myosin light chain phosphorylation, maximal shortening velocity (Vo), and isometric force. Maximal values of Vo [0.25 X optimal muscle length X s-1] and light chain phosphorylation (0.65 mol phosphate/mol light chain) were attained after 5 s of stimulation and preceded maximal force (60 s). Force gradually fell to 0.85 times maximal values during 30 min of stimulation, while both light chain phosphorylation and Vo declined to 0.3 times the maximal value. The temporal correlation between light chain phosphorylation and Vo supports the hypothesis that myosin phosphorylation in smooth muscle functions in regulating cross-bridge cycling rates. Myosin was dephosphorylated during relaxation with a half time of 2.7 s. Calculated maximal cellular rates of light chain phosphorylation were similar to measured values, indicating that most of the kinase was activated on stimulation. PMID- 4037072 TI - Effects of mucosal sodium removal on cell volume in Necturus gallbladder epithelium. AB - Necturus gallbladder epithelium transports sodium and chloride by a process that first involves the cellular entry of each ion across the apical membrane in an electrically silent process. In this paper we present results from cell volume and fluid flux measurements in the presence of different inhibitors and at normal and reduced sodium concentrations, which bear on the process by which ionic entry is effected. We find that reduction of mucosal sodium to a concentration of 10 mM has no effect on either cell volume or on the rate of transepithelial fluid transport, whereas the complete removal of sodium causes a significant decrease in cell volume in addition to its known inhibitory effect on fluid transport. Amiloride had no effect on cell volume at normal sodium concentrations but markedly reduced it when the sodium concentration was reduced to 10 mM. Amiloride, bumetanide, and dipyridamole markedly and reversibly inhibited fluid transport. Finally, the addition of ouabain to the serosal medium induced cell swelling, which was prevented by the removal of potassium from the mucosal medium. These results indicate that the process of sodium entry at the apical membrane is complicated and likely includes both cotransport (NaCl or Na-K-2Cl) and parallel exchange (Na-H and Cl-HCO3) transport mechanisms, and that the proportion of NaCl transported by the different mechanisms varies with the conditions. PMID- 4037073 TI - Control of enzyme activities in individual myotubes cultured without nerve. AB - The activities of lactate dehydrogenase, malate dehydrogenase, phosphorylase, and adenylate kinase were measured in single myotubes dissected from primary cultures of rat skeletal muscle. For a given enzyme, activities among the spontaneously contracting cells varied as much as eightfold. When the myotubes were paralyzed with tetrodotoxin, the variability in enzyme levels was markedly decreased. These and other findings suggest that differences in enzyme levels among individual myotubes may arise as a result of differences in their pattern of contractile activity. PMID- 4037074 TI - Potassium-chloride cotransport in cultured chick heart cells. AB - The polystrand preparation of cultured chick heart cells has a unidirectional transmembrane Cl- efflux that is twice K+ efflux. However, Cl- conductance of this heart cell membrane is low [regardless of extracellular K+ (K+o)], suggesting the existence of electroneutral Cl--dependent transport mechanisms. Furosemide (10(-3) M) decreases the 36Cl tracer efflux rate constant from a control value of 0.67 to 0.33 min-1. Extracellular Na+--free solution, which depletes intracellular Na+ within 1 min, has no significant effect on 36Cl efflux. K+o-free solution plus 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS; 10(-4) M) promotes the loss of Cl- against the Cl- electrochemical gradient; Cl- loss is furosemide sensitive in a dose-dependent manner. Incubating polystrands in 133 mM K+o, normal extracellular Cl- (Cl-o) solution causes net K+ and Cl- uptake in a 1:1 stoichiometry as well as a furosemide-sensitive volume increase; 130 mM extracellular choline or Li+ cannot mimic this high-K+o-induced volume increase. Removal of Cl-o from 133 mM K+o solution prevents K+ uptake and causes a Cl- loss as well as a furosemide-sensitive volume decrease. Adjusting Cl o concentrations in high-K+o solution plus DIDS, so that the Cl- chemical gradient equally opposes the K+ chemical gradient, prevents high-K+o-induced volume changes. These data suggest that the cardiac cell membrane contains a furosemide-sensitive K+-Cl- cotransport mechanism. PMID- 4037075 TI - A radioimmunoblotting method for measuring myosin light chain phosphorylation levels in smooth muscle. AB - A method for measuring the molar stoichiometry of myosin light chain phosphorylation in intact smooth muscle has been developed. Antiserum to the 20,000-Da light chains of bovine aortic smooth muscle was harvested from rabbits and used to label light chains by a radioimmunoblotting procedure. In the initial characterization it was found that the 20,000-Da light chains could be transferred by electroblotting from polyacrylamide gels to nitrocellulose paper with an efficiency of approximately 80% over a protein range of 0.1-5.0 micrograms. At a dilution of 1:500, the unpurified light chain antiserum required approximately 10-12 h at 22 degrees C to reach equilibrium binding to the transferred light chains. Moreover, equilibrium labeling of the light chain antibody complex with 125I-protein A required 4-6 h of incubation at 22 degrees C. By using these conditions, a radioimmunoassay for the 20,000-Da light chains was developed that was linear over a protein range of 0.1-5.0 micrograms (5-250 pmol). As little as 20 ng of light chains could be measured if a second antibody procedure (goat anti-rabbit immunoglobulin G Fab fragments) was used. Phosphorylated and unphosphorylated myosin light chains were separated by glycerol-urea polyacrylamide gel electrophoresis. This procedure, combined with radioimmunoblot, gave similar estimates of phosphorylation levels when compared with direct assay for phosphate or scanning of Coomassie blue-stained gels. Moreover, when applied to intact uterine smooth muscle, the glycerol-urea gel radioimmunoblot gave values of myosin light chain phosphorylation for relaxed and contracted muscles that were not statistically different from those obtained with a two-dimensional electrophoretic method.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4037076 TI - Changes in collagen synthesis and degradation during skeletal muscle growth. AB - The changes in collagen metabolism during skeletal muscle growth were investigated by measuring rates of synthesis and degradation during stretch induced hypertrophy of the anterior latissimus dorsi muscle of the adult chicken (Gallus domesticus). Synthesis rates were obtained from the uptake of tritiated proline injected intravenously with a flooding dose of unlabeled proline. Degradation of newly synthesized and "mature" collagen was estimated from the amount of hydroxyproline in the free pool as small molecular weight moieties. In normal muscle, the synthesis rate was 1.1 +/- 0.3%/day, with 49 +/- 7% of the newly produced collagen degraded rapidly after synthesis. During hypertrophy there was an increase of about fivefold in the rate of synthesis (P less than 0.01), a 60% decrease in the rate of degradation of newly synthesized collagen (P less than 0.02), and an increase of about fourfold in the amount of degradation of mature collagen (P less than 0.01). These results suggest an important role for degradative as well as synthetic processes in the regulation of collagen mass. They indicate that enhanced degradation of mature collagen is required for muscle growth and suggest a physiological role for the pathway whereby in normal muscle, a large proportion of newly produced collagen is rapidly degraded. PMID- 4037077 TI - Myosin phosphorylation in permeabilized rabbit psoas fibers. AB - The 18,000-Da myosin light chains in segments of rabbit psoas fibers were stably phosphorylated to assess the mechanical effects of this modification. Before and after phosphorylation of the same fiber, the maximal shortening velocity (Vmax) was measured at 12 degrees C by a quick-release slack test and by extrapolation to Vmax of hyperbolic force-velocity curves from isotonic releases. The experiments were performed at saturating concentrations of Ca2+, as determined from isometric force-pCa curves, under conditions in which the pH and ATP-ADP ratio were buffered. No effect of phosphorylation on isometric force, Vmax, or the shape of the force-velocity curve was detected under conditions of maximal calcium activation. Thus we find no mechanical evidence for a modulation by light chain phosphorylation of actomyosin interaction in these fiber segments. PMID- 4037078 TI - Premature weaning-induced changes of cholesterol metabolism in guinea pigs. AB - Premature weaning in animals causes higher serum cholesterol levels and a relative inability to handle cholesterol challenge in adult life. The mechanisms responsible for these delayed effects of premature weaning are not clear. The aims of this investigation were to 1) determine the effect of premature weaning on the activity of hepatic cholesterol 7 alpha-hydroxylase and plasma cholesterol changes and 2) determine whether addition of cholesterol to the diet will restore premature weaning-induced changes. Premature weaning did not prevent the phenomenon of neonatal hypercholesterolemia noted in day 5 of normally weaned guinea pigs. At day 10, prematurely weaned animals had lower serum cholesterol when compared with normally weaned animals. Premature weaning caused (without or with cholesterol in diet) a significant decrease in the hepatic activity of cholesterol 7 alpha-hydroxylase, and this difference persisted (after 1 mo) when fed the stock diet. These studies demonstrate 1) premature weaning on day 2 does not prevent neonatal hypercholesterolemia on day 5, 2) premature weaning causes a decrease in hepatic cholesterol 7 alpha-hydroxylase activity that persists into adult life, and 3) dietary cholesterol intake in early life is unable to negate premature weaning-induced changes. PMID- 4037079 TI - Effect of norepinephrine on gluconeogenesis in perfused livers of cold-exposed rats. AB - The effects of norepinephrine and glucagon on gluconeogenesis were studied in hemoglobin-free perfused liver from rats kept for 1-20 days at 4 degrees C. When rats were starved for 24 h at 4 degrees C, the plasma glucose level of rats exposed to cold for 5, 10, and 20 days was significantly higher than that of rats for 1 day, but hepatic glycogen decreased to the same level in all groups. In the isolated perfused liver, basal rates of oxygen consumption and glucose production increased slightly through 5 days of cold exposure and returned to control levels after 20 days of cold exposure. The rates of glucose production from lactate, pyruvate, sorbitol, and glycerol increased by 20-30% after 5 days of cold exposure. The stimulation of gluconeogenesis from these substrates by norepinephrine and phenylephrine increased markedly at all time periods from 1 to 20 days in the cold, with a maximum at 5 days. The stimulation of glycogenolysis by norepinephrine was not affected by cold exposure. The response to catecholamines decreased markedly in liver perfused with calcium-free medium and/or with phentolamine. The stimulation of gluconeogenesis by glucagon increased only in rats exposed to cold for 20 days. The results obtained suggest that the stimulation of hepatic gluconeogenesis by cold is due to an alpha adrenergic response, and the activation occurs beyond the interaction of norepinephrine with its receptor. PMID- 4037080 TI - Regulation of sympathetic activity in lean and obese Zucker (fa/fa) rats. AB - Norepinephrine concentration and turnover (measured by the time-dependent loss of tissue [3H]norepinephrine specific activity) were reduced in the brown adipose tissue (BAT) of obese Zucker rats but were normal in the heart. After acclimation to a 4 degrees C environment for 7 days, BAT norepinephrine turnover was increased to similar levels in lean and obese rats. After overfeeding with sucrose BAT norepinephrine turnover increased in lean rats but was unaffected in obese rats. Propranolol prevented the normalization of BAT mitochondrial GDP binding that followed adrenalectomy of obese rats. Adrenalectomy of obese rats restored BAT norepinephrine turnover to levels observed in lean rats. However, the increase in BAT GDP binding associated with sucrose overfeeding of adrenalectomized lean and obese rats was neither prevented by propranolol nor associated with a stimulation of norepinephrine turnover. The results suggest that the pituitary-adrenal endocrine axis may influence diet-related BAT thermogenesis and that this influence is only partially mediated by the sympathetic nervous system. PMID- 4037081 TI - Maternal fetal glucose exchange. PMID- 4037082 TI - Systemic and splanchnic hemodynamic disturbances in conscious rats with experimental liver cirrhosis without ascites. AB - Rats with CCl4-induced cirrhosis of the liver show histological and clinical features that closely resemble those of the disease in humans. Metabolic cages were used and hemodynamic studies (15-micrograms radioactive microspheres) were performed on 10 conscious, nonascitic, cirrhotic rats and in 10 control rats. Compared with control animals, cirrhotic rats showed lower sodium excretion (0.80 +/- 0.07 vs. 1.01 +/- 0.07 meq/day), total solute excretion (12.52 +/- 0.79 vs. 19.38 +/- 3.7 mosmol/day), and increased aldosterone excretion. No differences were observed in urinary epinephrine and norepinephrine excretion. Cirrhotic rats showed also slight hypotension, increased cardiac output (48.97 +/- 3.94 vs. 26.97 +/- 2.3 ml X min-1 X 100 g-1) without tachycardia, and decreased total peripheral resistance, which was mainly attributed to reduced renal and skeletal muscle resistances with increased blood flow throughout these areas. Cirrhotic rats showed increased hepatic vascular resistances by both portal and arterial inputs with portal hypertension (16.15 +/- 1.01 vs. 9.60 +/- 0.77 cmH2O) but without differences in total hepatic blood flow or portal-systemic shunt rate with respect to control rats. Plasma renin content was not significantly different between the groups of rats. From these data it can be concluded that nonascitic, cirrhotic rats show a hyperdynamic circulatory state, which seems to be caused by a peripheral vasodilation of unknown mechanism; portal-systemic shunting does not seem to be a necessary condition for the hyperdynamic status at this early stage of the hemodynamic disturbances. PMID- 4037083 TI - Methionine metabolism after portacaval shunt in the rat. AB - The effect of portacaval shunt (PCS) on methionine metabolism in the rat was investigated. Male Sprague-Dawley rats were subjected to PCS and maintained on an 18% casein diet. Growth curves of operated rats were similar to controls. PCS rats excreted more urinary 35SO4 and less [35S]taurine than controls after intraperitoneal injection of 0.3 mmol/100 g [35S]methionine or [35S]cysteine. Total urinary taurine excretion was similar in PCS and control rats after a methionine or cysteine load; however, under basal conditions PCS rats had higher urinary taurine levels than controls, indicating that PCS may cause the taurine pool to be expanded. Hepatic methionine, S-adenosylmethionine, and cysteine pools were significantly decreased in PCS rats, while S-adenosylhomocysteine levels were unchanged. Relative rates of transsulfuration in PCS and control rats were studied by following the decrease in the 3H-to-35S ratio in liver protein after injection of [methyl-3H]methionine and [35S]methionine, and no difference in flux of 35S from [35S]methionine to [35S]cysteine was found. Similarly, total hepatic activities of methionine adenosyltransferase, cystathionine synthase, and cystathionine gamma-lyase were unchanged in PCS rats. These results indicate that altered methionine metabolism in PCS rats is not explained by changes in conversion of methionine to cysteine via the transsulfuration pathway. PMID- 4037084 TI - Age-related changes in rat intestinal transport of D-glucose, sodium, and water. AB - Experiments were performed with everted sacs of jejunum and ileum and brush border membrane vesicles from four different age groups of rats: very young, young, adult, and old. The changes with age in several parameters, such as cell electrolyte and D-glucose concentrations, cell volume, net D-glucose, Na+ and water transport, and D-glucose uptake into vesicles, were studied. Differences in transport activities in the four age groups of animals were observed. In the jejunum the greatest transport was found in young rats and less in adult, very young, and old rats. In the ileum, the greatest transport activity was found in very young and young rats, while in adult and old animals transport activity was negligible. The cell volume of the enterocyte was significantly smaller in old rats. Changes in cell electrolytes (increased Na+ and decreased K+) were observed only in the jejunum of old rats. The overshoot of D-glucose in brush-border membrane vesicles varied considerably in the four different age groups of animals. In other words, the capacity for sugar uptake into vesicles is greater in young rats than in very young or adult animals. In old rats there was no overshoot, and a slow linear increase of sugar entry was observed. The results indicate that the changes in D-glucose transport with age might be explained in part by the changes in the amount of sugar that crosses the brush-border membrane of the enterocyte. PMID- 4037085 TI - Tone of canine ileocolonic junction: topography and response to phasic contractions. AB - We wished to define the physiology of the canine ileocolonic sphincter (ICS) and to examine function in relation to the region's anatomy. Prolonged recordings of tone at the ICS were made from seven dogs with isolated ileocolonic loops, and the effects of ileal and colonic distension on sphincteric tone were assessed. In acute experiments, pull-through pressures were measured at the ICS, and the location of the high-pressure zone was related to the region's anatomy. Basal tone at the ICS of approximately 30 cmH2O was confirmed; tone was augmented by colonic and ileal distension. The high-pressure zone was always centered on the anatomic ICS, but it extended into the adjacent ileum and colon for a total length of 2.0 cm (range 1.5-3.0 cm). Phasic contractions contributed to the maintenance of tone at the ICS, and a coordinated pattern of phasic contractions appears to contribute to the sphincteric properties of the region. PMID- 4037086 TI - Countercurrent exchange of water in canine jejunum. AB - The possibility of countercurrent exchange of water molecules in canine intestinal villi has been examined. Tritium-labeled water (3H2O) molecules were introduced either into the fluid lavaging the intestinal lumen or into the arterial blood supply for varying periods of time. Quickly frozen samples of intestinal tissue were sectioned such that isotopic concentrations at the villus tip, midvillus, villus base, and underlying submucosa and muscle could be determined. The villus concentration gradients observed were consistent with the existence of a countercurrent exchange but could also be explained by alternative arrangements. More convincing evidence of a countercurrent was obtained from experiments in which [14C]inulin was introduced simultaneously with 3H2O into the intestinal artery. The villus tip-to-base concentration ratio for 3H2O was less than one while the ratio for inulin was greater than one, thus vitiating the alternative explanations and leading to the conclusion that the labeled water molecules must have undergone a countercurrent exchange. PMID- 4037087 TI - Dietary fat assimilation and bile salt absorption in the killifish intestine. AB - Radiolabeled taurocholate (TC) and triolein were used to study fat assimilation and bile salt absorption in the stomachless saltwater killifish, Fundulus heteroclitus. Fat absorption occurred primarily in the proximal intestine with approximately 87% of a single dose (9 mg fat/8 g fish) absorbed in 2 h. Luminal triolein hydrolysis and enterocyte triolein resynthesis were tightly coupled. Killifish gallbladder bile contains taurocholate and cholate in an equal molar ratio at a combined concentration of 237 +/- 25 mM (n = 10) in 24-h-fasted fish. During fat assimilation luminal bile salt and fatty acid concentrations ranged between 10 and 30 mM. Between and during meals the total concentration of bile salts in the intestinal tissue remained roughly constant (4-6 mM) with the proximal one-third of the intestine containing 40% of the total and the remainder equally distributed between the mid and distal regions. All three regions of the intestine rapidly incorporated ingested TC in vivo, with the amount incorporated proportional to the pool size. In contrast, in vitro at low TC concentrations (60 nM), the distal one-third of the intestine incorporated 10 times as much TC in 2 min uptake experiments as the proximal and mid regions. Although there are many similarities between fat and bile salt assimilation in killifish and mammals, overall the processes are much simpler in killifish. PMID- 4037088 TI - Na+ gradient-dependent glycine uptake in basolateral membrane vesicles from the dog kidney. AB - The imposition of a Na+ gradient (extravesicular greater than intravesicular) stimulated the uptake of [3H]glycine measured over time in basolateral membrane vesicles from dog kidney over that measured in the presence of a choline+ gradient or measured under Na+-equilibrated conditions. Na+ gradient-dependent uptake of [3H]glycine was stimulated by an intravesicular-negative membrane potential. Efflux of [3H]glycine was enhanced by an intravesicular-positive membrane potential. Substrate velocity analysis of net Na+-dependent [3H]glycine uptake over the range of amino acid concentrations from 10 to 500 microM demonstrated a single saturable transport system with apparent Km = 84 microM and apparent Vmax = 143 pmol [3H]glycine X mg protein-1 X 15 s-1. Counterflow of [3H]glycine was demonstrated in the presence of Na+ when basolateral vesicles were preloaded with glycine but not with L-alanine or L-proline. These findings are consistent with carrier-mediated, electrogenic cotransport of Na+ and glycine in basolateral vesicles. Unlike the case for [3H]glycine, Na+ gradient-dependent uptake of neither L-[3H]alanine nor L-[3H]proline was observed in basolateral vesicles. Na+ gradient-dependent uptake of all three amino acids was demonstrated in brush border vesicles from the dog kidney. We conclude that variability exists between basolateral and brush border membranes in terms of the presence or absence of Na+-dependent transport systems for specific amino acids. This variability probably reflects differences between the functional significances of the Na+-dependent transport processes in the two membranes. PMID- 4037089 TI - Effect of pentobarbital and hemorrhage on renal autoregulation. AB - Renal blood flow and hemodynamic autoregulation were assessed in seven chronically instrumented canines studied in the conscious state and after pentobarbital anesthesia administration (30 mg/kg). The effects of acute arterial hemorrhage (10 and 15 ml/kg) were also studied. In the conscious state, no significant changes in autoregulation were observed following 10 mg/kg hemorrhage. With pentobarbital and 10 ml/kg hemorrhage, a significant change in the limits of autoregulation was noted (autoregulatory limit 78.5 +/- 16.6 vs. 88.4 +/- 25.3 mmHg, P less than 0.05). Four animals were also studied in the conscious state following 15 ml/kg acute arterial hemorrhage. In these animals, mean arterial pressure decreased (from 105.0 +/- 11.4 to 87.8 +/- 7.2 mmHg, P less than 0.025) but renal blood flow (from 293 +/- 38 to 272 +/- 65 ml/min) and autoregulatory limit did not change. We conclude that renal blood flow is unaffected by hemorrhage or pentobarbital alone. In the conscious state, renal pressure-flow autoregulation is maintained despite moderate hemorrhage and systemic hypotension. The lower limit of autoregulation is significantly changed by even minor hemorrhage in the pentobarbital-anesthetized state. PMID- 4037090 TI - Heteroporous model of glomerular size selectivity: application to normal and nephrotic humans. AB - A heteroporous model of the glomerular filtration barrier was developed and used to interpret dextransieving data in healthy volunteers (normal controls), in patients with nephrotic range proteinuria (grouped as grades I-III, according to severity), and in a group of previously nephrotic patients whose proteinuria was in remission ("resolved controls"). Several hypothetical pore-size distributions were compared in terms of their ability to describe the selective increases in the fractional clearance of large dextrans observed with increasing severity of proteinuria. The most successful model examined was based on the assumption that the major portion of the capillary wall functions as an isoporous membrane, but that a small fraction of the filtrate passes through pores that are unable to discriminate among dextrans of different sizes. The value of the membrane parameter that reflects the relative importance of the nonselective pores was found to increase in parallel with the fractional clearance of immunoglobulin G; it increased progressively in going from normal controls to resolved controls to grades I-III nephrotics. The observed patterns of protein excretion could not, however, be explained entirely by a loss of glomerular size selectivity. Variations in membrane selectivity on the basis of molecular charge and/or molecular configuration are also likely to have been important. PMID- 4037091 TI - Renal interstitial pressure in mineralocorticoid escape. AB - Studies were performed in normal and DOCA-treated rats to determine renal hydrostatic pressures within superficial peritubular capillaries, the vasa recta, and renal interstitium during mineralocorticoid escape to test the hypothesis that mineralocorticoid escape is associated with elevated renal interstitial hydrostatic pressure. Fractional sodium excretion was greater in the DOCA-treated rats (3.20 +/- 0.51%) compared with control rats (1.23 +/- 0.12%) with no difference in glomerular filtration rate and renal blood flow between the two groups. Superficial peritubular capillary hydrostatic pressure (13.4 +/- 0.6 vs. 8.3 +/- 0.3 mmHg), vasa recta hydrostatic pressure (13.8 +/- 0.5 vs. 9.0 +/- 0.4 mmHg), renal interstitial hydrostatic pressure (9.8 +/- 0.4 vs. 4.5 +/- 0.4 mmHg), and arterial pressure (145 +/- 6 vs. 120 +/- 7 mmHg) were greater in the DOCA-treated compared with the control rats. These studies establish that mineralocorticoid escape is characterized by high renal interstitial hydrostatic pressure. PMID- 4037092 TI - Sodium-pyrazinoate cotransport in rabbit renal brush border membrane vesicles. AB - Pyrazinoate (PZA) is an organic anion actively reabsorbed and secreted in the mammalian kidney. In experiments with rabbit renal brush border membrane vesicles, we characterized a sodium-PZA cotransport mechanism that could be involved in reabsorption. An inwardly directed sodium gradient stimulated the influx of PZA. The sodium-dependent transport was electroneutral, suggesting a 1:1 stoichiometry. The kinetic constants for sodium-PZA cotransport were measured under initial linear flux and zero trans conditions for both sodium and PZA. The apparent Km for sodium was about 60 mM. At 90 mM sodium the apparent Km for PZA was about 1.1 mM; increasing the sodium concentration augmented the apparent affinity for PZA. Cis inhibition of sodium-dependent PZA uptake was observed by the addition of nicotinate, lactate, probenecid, succinate, beta-hydroxybutyrate, and salicylate. Urate had no effect. [14C]PZA uptake was trans stimulated by PZA itself, lactate, and nicotinate. PZA shares a transport system(s) involved in the proximal tubular reabsorption of these two anions. PMID- 4037093 TI - Intracellular pH in the isolated perfused rabbit proximal straight tubule. AB - For the purpose of measuring the intracellular pH (pHi) of the mammalian renal proximal tubule, a liquid membrane pH microelectrode was made using a neutral hydrogen ion-selective carrier. The pHi of the rabbit proximal straight tubule perfused in vitro with a solution containing 25 mM HCO3- was 7.22 +/- 0.03. We noted a value significantly lower than the bath pH of 7.44 +/- 0.02 but significantly higher than the pHi of 6.62 +/- 0.03 predicted for passive H+ distribution. Replacement of luminal Na+ with choline quickly (within 1 min) decreased pHi from 7.25 +/- 0.05 to 7.10 +/- 0.05 (P less than 0.001). This change was reversible when Na+ was added again in the luminal solution. A reduction of luminal Na+ from 20 mM to 0 also reduced pHi from 7.15 +/- 0.06 to 7.04 +/- 0.08, and this pHi reduction was blocked by luminal addition of 1 mM amiloride. However, pHi reduction induced by luminal Na+ removal was not affected by luminal addition of 1 mM SITS. Replacement of bath Na+ with choline also reversibly reduced pHi from 7.27 +/- 0.02 to 7.15 +/- 0.02 (P less than 0.001), but this change was totally blocked by the presence of 1 mM SITS. Accordingly, these data suggest that a Na+-H+ exchanger exists in the luminal membrane of the intact rabbit proximal straight tubule. PMID- 4037094 TI - Hypotension 1.5 min after 10% hemorrhage permits evaluation of rabbit's baroreflex. AB - In seven chronically instrumented rabbits, we studied the influence of the vasopressin system on the evaluation of acute reflex compensation of arterial pressure for a mild hemorrhage. Rabbits were bled 10% of estimated blood volume in 1 min. The hemorrhage was repeated before and after administration of a vasopressin antagonist [d(CH2)5Tyr(Me)arginine vasopressin, 10 micrograms/kg] and in the conscious and anesthetized (pentobarbital sodium 20 mg/kg) state. The efficacy of the vasopressin antagonist was preliminarily tested in each rabbit by confirming its antagonism against the hemodynamic effects of infused vasopressin (50 ng X min-1 X kg-1). Mean arterial pressure (MAP), heart rate (HR), mean aortic flow (MAF), and total peripheral resistance (TPR) were measured before and at 1.5 min after completion of hemorrhage. The hemorrhage caused statistically significant decrease in MAP (84 +/- 6 to 78 +/- 6 mmHg) and MAF (195 +/- 28 to 158 +/- 26 ml X kg-1 X min-1) and increase in TRP (0.44 +/- 0.05 to 0.51 +/- 0.07 mmHg X kg X min X ml-1) and HR (271 +/- 21 to 284 +/- 22 beat/min). However, there was no statistically significant interaction in any variables between vasopressin and hemorrhage, i.e., whether vasopressin was blocked or intact did not affect the fall in MAP by hemorrhage. We conclude that in the rabbit vasopressin's role in the acute compensation of arterial pressure for a quick 10% hemorrhage is small enough to permit accurate estimation of the arterial baroreflex gain from the depressor responses to mild hemorrhage with and without the reflex function. PMID- 4037095 TI - Nicotine increases heart adenosine release, oxygen consumption, and contractility. AB - The effect of nicotine on adenosine release, oxygen consumption, and contractility was investigated in perfused rat hearts. Continuous infusion of nicotine into the perfusing physiological saline (PS) elicited a propranolol (10( 6) M) sensitive transient elevation of developed left ventricular pressure (LVP) and maximum rates of left ventricular pressure development and relaxation (+/- dP/dtmax) within 20 s, which subsequently declined to maintained elevated plateau levels by 1 min. The continuous infusions of nicotine to achieve PS concentrations of 5 X 10(-4), 1 X 10(-4), or 5 X 10(-5) M, respectively resulted in significant increases in the mean plateau levels of LVP (33.4, 10.1, or 6.3%), +dP/dtmax (26.3, 10.8, or 6.9%) and-dP/dtmax (35.0, 11.9, or 9.0%) at 1 min. The inclusion of propranolol (10(-6) M) with or without atropine (10(-6) M) did not alter these maintained plateau responses to nicotine. During the plateau phase of the contractile response oxygen consumption of the hearts was significantly elevated by 36, 19, or 11%, and mean levels for adenosine in the coronary effluent rose by 261, 76, or 74% in response to 5 X 10(-4), 1 X 10(-4), or 5 X 10(-5) M nicotine, respectively. Nicotine did not influence [14C]adenosine uptake by the hearts. These results suggest that nicotine is capable of 1) augmenting cardiac contractility and oxygen consumption independent of beta-adrenergic or muscarinic influence, and 2) elevating the appearance of adenosine in the coronary circulation presumably by enhancing myocardial production of the nucleoside. PMID- 4037096 TI - Measurement of calcium influx in tethered rings of rabbit aorta under tension. AB - Calcium (Ca) influx in vascular smooth muscle is routinely measured in untethered preparations not under passive stretch, and Ca influx data are correlated with data for steady-state isometric tension obtained under parallel conditions from tethered preparations under passive stretch. The validity of this method was tested by simultaneous measurement of Ca influx and tension in tethered rings of rabbit thoracic aorta. Ca influx (45Ca 3-min pulse) and tension were measured at 3 and 30 min after norepinephrine (NE) or KCl and under control (no agonist) conditions. Active tension was significantly altered by variations in passive tension. Ca influx was unaffected by passive tension under control, NE, or KCl conditions, and results were similar at 3 and 30 min. The results confirm the validity of correlating Ca influx data from untethered rings with steady-state contractile response data obtained from tethered rings under similar experimental conditions. PMID- 4037097 TI - Effects of peptide leukotrienes on cardiac dynamics in rat, cat, and guinea pig hearts. AB - The purpose of the present investigation was to examine potential inotropic effects of leukotrienes C4 (LTC4) and D4 (LTD4) in relation to their potent coronary constricting effects. The experiments were carried out in isolated Langendorff perfused hearts and isolated electrically driven isometrically contracting papillary muscle preparations. Tissues from cat, rat, and guinea pig were used in the study. Both LTC4 and LTD4 at 50 ng/ml had no effect on papillary muscles isolated from the rat, guinea pig, or cat. These papillary muscles responded to known negative inotropic agents including pentobarbital sodium and methanol. In isolated hearts perfused under constant flow, both LTC4 and LTD4 at 50 ng/ml increased coronary perfusion pressure and decreased contractile force of the heart in all three species. In hearts perfused under constant pressure perfusion, both LTC4 and LTD4 decreased coronary flow with concomitant decreases in contractile force. The leukotriene antagonist, FPL 55712, blocked both the coronary constrictor and the cardiodepressant effects of both leukotrienes. Pentobarbital (100 micrograms/ml) significantly decreased cardiac contractile force without inducing coronary vasoconstriction. These findings demonstrate that LTC4 and LTD4 do not possess direct negative inotropic activity in cardiac muscles of these three species. However, LTC4 and LTD4 are potent coronary constrictors that can secondarily decrease myocardial contractile force via their coronary constrictor action. PMID- 4037098 TI - Age-related changes in regional blood flow in the rat. AB - The purpose of this investigation was to characterize the changes in regional blood flow and central hemodynamic measures that occur in the rat as a result of the aging process. The isotope-labeled microsphere technique was used to measure cardiac output and regional blood flows in conscious and anesthetized adult (12 mo) and senescent (24 mo) Fischer 344 virgin female rats. No significant changes were observed in central hemodynamic measurements or regional blood flows in conscious rats with the exception of a 25% reduction in splenic blood flow. Pentobarbital anesthesia significantly reduced cardiac index and heart rate but elevated total peripheral resistance and mean arterial blood pressure. There was a decrease in blood flow to skeletal muscle, spleen, duodenum, stomach, and brain tissue samples and increased hepatic arterial blood flow in both age groups. The use of anesthesia caused a greater reduction in the cardiac index and brain blood flow in the senescent anesthetized rats than in the adult rats. Heart and kidney blood flows were decreased by anesthesia in the senescent rats but not in the adult rats. Skeletal muscle blood flow, however, was significantly greater in the senescent anesthetized rats than in the younger anesthetized animals. Although body weight and organ weights of the liver, spleen, kidneys, stomach, heart, and brain were significantly greater for the senescent rats, no differences could be demonstrated in tibial length or lean body mass. PMID- 4037099 TI - Recovery of ventricular function in reperfused ischemic rat hearts exposed to fatty acids. AB - The relationship between tissue levels of fatty acid metabolites in ischemic and reperfused hearts and recovery of mechanical function of these hearts on reperfusion was studied. Isolated rat hearts were exposed to global ischemia for periods up to 60 min under various conditions of coronary flow, O2 supply, and fatty acid concentrations and were then reperfused for either 15 or 30 min under aerobic conditions both with and without fatty acids present. Tissue levels of ATP, creatine phosphate, long-chain acyl CoA, and long-chain acyl carnitine were determined at the end of the ischemic and reperfusion periods. In some experiments K+ arrest during ischemia was used to prevent adenine nucleotide depletion both in the absence and presence of high fatty acids. Although the ability of these hearts to recover their preischemic mechanical function varied from 8 to 90% and tissue levels of acyl CoA and acyl carnitine during ischemia varied from 3- to 10-fold depending on the condition, no correlation was found between the recovery of function during reperfusion and either the presence of fatty acid or high levels of tissue long-chain acyl CoA and carnitine esters during ischemia. PMID- 4037100 TI - Microvascular pressure, surface area, and permeability in isolated hindquarters of SHR. AB - The transvascular escape rate (TER) of labeled albumin is reported to increase in essential hypertension. However, the mechanism for this augmented rate of protein efflux is uncertain and may be related to increased microvascular permeability, surface area, and/or pressure. To determine the possible contributions of these mechanisms to increased TER of protein, the osmotic reflection coefficient for total plasma protein, capillary filtration coefficient, and effective capillary pressure were estimated in isolated hindquarters of age-matched (12-13 wk) spontaneously hypertensive (SHR), Wistar-Kyoto (WKY), and Wistar (WR) rats. Estimates of the reflection and filtration coefficients were not significantly different in SHR, WKY, and WR. However, capillary pressure was significantly greater in SHR than in normotensive controls. These results indicate that 1) skeletal muscle microvascular permeability and surface area are similar in SHR, WKY, and WR; 2) effective capillary pressure is greater in SHR than WKY or WR; and 3) if TER for protein is elevated in hypertensive skeletal muscle, the primary mechanism for this process may be increased convective transport of protein secondary to elevated microvascular hydrostatic pressure. PMID- 4037102 TI - Myocardial perfusion in compensated and failing hypertrophied left ventricle. AB - This study examined blood flow in the hypertrophied left ventricle with and without failure. Left ventricular hypertrophy was produced in 20 dogs by banding the ascending aorta at 6-7 wk of age; studies were performed after animals reached adulthood. Sixteen dogs had compensated hypertrophy, while four dogs had cardiac failure manifested by left ventricular dilatation and end-diastolic pressures greater than 18 mmHg. The degree of hypertrophy, assessed by left ventricular-to-body weight ratio, was similar in animals with compensated hypertrophy (7.29 +/- 0.26 g/kg) and failure (8.45 +/- 0.15); both were greater than control (4.50 +/- 0.15, P less than 0.01). Left ventricular systolic pressure was similar in compensated hypertrophy (184 +/- 9 mmHg) and failure (226 +/- 29), as compared with control (130 +/- 4; P less than 0.01). Left ventricular blood flow measured with microspheres was 0.89 +/- 0.07 ml X min-1 X g-1 in control animals, was increased to 1.34 +/- 0.05 with compensated hypertrophy (P less than 0.001), and was further increased with failure to 1.86 +/- 0.40 (P less than 0.05). The left ventricular wall thickness-to-cavity diameter ratio was increased to 0.63 +/- 0.04 with compensated hypertrophy but was only 0.40 +/- 0.05 in dogs with failure (P less than 0.01), suggesting that wall stress was greater in hearts with failure. These data suggest that increased blood flow rates in dogs with failure resulted from increased myocardial O2 requirements due to increased systolic wall stress. Need for increased blood flow during resting conditions in dogs with failure would impair the ability for further coronary vasodilation during periods of cardiac stress. PMID- 4037101 TI - Relationship between caffeine effects and calcium in canine cardiac Purkinje fibers. AB - The actions of caffeine (1-9 mM) on electrical and mechanical events were studied under conditions known to change the intracellular calcium in canine cardiac Purkinje fibers perfused in vitro. It was found that caffeine in a dose-dependent manner 1) shifts the early repolarization to more positive values, 2) shifts the plateau to more negative values, 3) prolongs the terminal phase 3 (induction of a "tail"), 4) transiently increases and then decreases the force of contraction with respect to control values, 5) causes a smaller tail in the presence of agents (local anesthetics, tetrodotoxin, high potassium) that have been shown to diminish the force of contraction, presumably by decreasing cellular calcium, 6) causes the oscillatory potentials in high calcium to peak sooner after the action potential and eventually to disappear as the tail develops, 7) induces a tail at lower concentrations when cellular calcium is enhanced by lowering the external sodium concentration or in the presence of veratridine, and 8) fails to induce a marked tail in the presence of metabolic inhibitors. It is concluded that in Purkinje fibers caffeine induces a marked delay in the final repolarization through a process modulated by calcium. This process may be related to an electrogenic sodium-calcium exchange. PMID- 4037103 TI - Standardization of end-systolic pressure-volume relation in the dog. AB - Left ventricular (LV) volume elastance (Emax) and its volume intercept (Vo) are subject to considerable intersubject and interspecies variation. In humans, indexing with body surface area does not decrease variance. Because these are volume indexes, it was considered they would better standardize against body or LV weight. Fifteen open-chest mongrel dogs (mean wt 25.9 +/- 8.0 kg, range 15.6 42.5) were studied under 1% halothane anesthesia. Emax, derived by caval occlusion, averaged 9.0 +/- 4.4 mmHg X ml-1 (range 4.1-16.1) with a coefficient of variation (CV) of 48%. Average Vo was 19.6 +/- 10.5 ml (range 8.3-40.3) with a CV of 53%. LV weight was 110 +/- 21 g (range 78-147). Vo correlated best with LV weight: Y = 0.47 X - 31.78, r = 0.93, and adjustment of Vo by regression reduced CV to 20%. Emax was closely correlated with either 1/dog wt [Y = 313.02 (1/X) - 4.16, r = 0.88, CV = 23% after adjustment by regression] or 1/LV wt [Y = 2088.63 (1/X) - 10.72, r = 0.86, CV = 25% after adjustment]. Indexing of Emax by dog weight (CV = 29%) or LV weight (CV = 35%) reduced variation but by less than adjustment by regression. A subset of eight dogs had inotropic state varied, which had no effect on the relation between Vo and LV weight, but which resulted in an appropriate change (P less than 0.025) in the relation between Emax and 1/LV wt.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4037104 TI - Modeling of time-variant coupling between left ventricle and aorta in cardiac cycle. AB - An analytical model is developed to study the interaction between the left ventricle and vascular system. Ventricular pressure is expressed as a function of the chamber volume, volumetric strain rate, and the degree of activation. A three element Wind-kessel model is employed to represent the hydraulic properties of the vascular system. Conditions of interaction between the left ventricle and the vascular system are formulated in mathematical terms. Numerical solutions are obtained for the mechanical events occurring during a cardiac cycle as a function of time. The time variations of aortic pressure and ventricular volume predicted by the model compare well with the experimental results of Sunagawa and co workers [Am. J. Physiol. 243 (Heart Circ. Physiol. 12): H346-H350, 1982, and Am. J. Physiol. 245 (Heart Circ. Physiol. 14): H773-H780, 1983]. Furthermore, the application of the present model to the experimental data has allowed the derivation of the intrinsic contractility parameters in these experiments. The unique features of this analytical model are that 1) it provides the time-variant pressure and volume curves of the left ventricle in relation to the aorta, 2) it generates information on the effects of heart rate on these hemodynamic parameters, and 3) it allows the derivation of intrinsic contractility parameters from experimental data. PMID- 4037106 TI - Measurement of peak systolic elastance in intact canine circulation with servo pump. AB - Peak systolic elastance (Emax) was measured in the intact canine circulation by means of a new experimental technique. In this technique the heart is isolated from the circulation during a single systole and subjected to controlled ventricular loads. An electropneumatic aortic occluder is used to isolate the ventricle, and a servo-controlled syringe pump is used to control the ventricular load. Because the experimental load is applied for a single heartbeat only, ventricular function can be measured without the interference of regulatory feedback mechanisms. In eight dogs, weighing 17-42 kg, the relationship between changes in endsystolic pressure and volume was determined from the single-beat application of purely compliant loads. The end-systolic relations were linear, and their slope, Emax, was inversely related to weight. The observed relation between Emax and body weight allows comparisons to be made between different preparations in which Emax has been determined. Values of Emax obtained from the single-beat preparation were found to be 27-74% above those reported in isolated heart preparations and nearly identical to those reported for in vivo or denervated in situ preparations. PMID- 4037105 TI - Leukotriene end organ antagonists increase pulmonary blood flow in fetal lambs. AB - The factors responsible for maintaining the normally low pulmonary blood flow and high pulmonary vascular resistance in the fetus are not well understood. Since leukotrienes are potent pulmonary vasoconstrictors in many adult animal species, we determined whether leukotrienes were perhaps involved in the control of the fetal pulmonary circulation by studying the effects of putative leukotriene end organ antagonists in two groups of fetal lambs. In six fetal lambs studied at 130 134 days gestation, FPL 55712 increased pulmonary blood flow by 61% (P less than 0.05) and reduced pulmonary vascular resistance by 45% (P less than 0.05). There was a small increase in heart rate but no changes in pulmonary and systemic arterial pressures and systemic arterial blood gases. In six other fetal lambs studied at 130-140 days gestation, FPL 57231 increased pulmonary blood flow by 580% (P less than 0.05) and decreased pulmonary vascular resistance by 87% (P less than 0.05). Pulmonary and systemic arterial pressures decreased (P less than 0.05), and heart rate increased (P less than 0.05). Leukotriene end organ antagonism significantly increases fetal pulmonary blood flow and decreases pulmonary vascular resistance. Leukotrienes may play a role in the physiological control of the fetal pulmonary circulation. PMID- 4037107 TI - Electrophysiology of functional subsidiary pacemakers in canine right atrium. AB - Glass microelectrodes were used to study the electrical activity of the subsidiary atrial pacemaker (SAP) cells that maintain atrial excitation after suppression of the sinoatrial node. Tissues with documented SAP activity were isolated from the canine inferior right atrium and superfused in vitro with Tyrode solution containing norepinephrine (NE, 10(-8)-10(-7) M). SAP action potentials exhibited prominent diastolic depolarization and a significantly lower maximum diastolic potential, take-off potential, overshoot, rate of rise, and amplitude than typical atrial muscle. Withdrawal of NE completely blocked SAP propagation, although SAP automaticity continued at a slower rate. Acetylcholine (ACh, 5 X 10(-8) M) usually produced complete exit block and decreased spontaneous rate. Higher concentrations of ACh (10(-6) M) elicited a prominent hyperpolarization (19.2 +/- 6.6 mV), completely suppressing SAP automaticity. In quiescent preparations exposed to NE greater than or equal to 10(-7) M, external stimuli at short cycle lengths (less than 1,000 ms) elicited action potentials with delayed afterdepolarizations, which frequently caused nondriven repetitive activity. This triggered activity was inhibited by verapamil or withdrawal of NE. These studies identify and characterize the electrical activity of functional subsidiary pacemakers located in a specific region of the inferior right atrium. In addition, fibers within this region display triggered activity. Spontaneous activity generated by fibers within the SAP region may cause atrial dysrhythmias. PMID- 4037108 TI - Effects of anoxia and ischemia on thallium exchange in rabbit myocardium. AB - We investigated the effects of anoxia and ischemia on thallium (201Tl) exchange using isolated rabbit interventricular septa. Anoxia for 20 or 40 min caused a decrease in 201Tl tissue uptake due to an increased efflux of 201Tl with a smaller increase in 201Tl influx. Between 40 and 60 min of anoxia, the increased efflux of 201Tl was reversed and the increase in 201Tl influx was absent. After 60 min of reoxygenation, septa made anoxic for 20-60 min recovered at least 95% of the Tl lost. Mechanical recovery, however, was still significantly depressed. Reperfusion after total ischemia for 20-60 min was followed by resumption of 201Tl uptake despite continued mechanical dysfunction. Efflux rates during reperfusion after ischemia were significantly different from preischemic values but not in a predictable way. This unpredictability complicates interpretation of clinical 201Tl redistribution studies. These results represent important differences from those reported previously using 42K [Am. J. Physiol. 232 (Heart Circ. Physiol. 1): H85-H94 and H564-H570, 1977]. Anoxia did not increase the influx of 42K. Also, 60 min of ischemia resulted in progressive losses of 42K. This implies there are different sensitivities and/or mechanisms for Tl compared with K uptake. Our results are consistent with 201Tl uptake by severely damaged and nonviable cells. PMID- 4037109 TI - Incomplete coronary vasodilation during myocardial ischemia in swine. AB - To determine if endogenous (ENDG) vasodilation was maximum during myocardial ischemia, left anterior descending (LAD) mean pressure (P) was reduced for 20 min in 13 swine. At LAD P of 45 mmHg (LAD P45) flow fell during ENDG = 25 but rose to 44 ml/min during adenosine (AD) infusion (P less than 0.01). Flow increased to subendocardium (ENDG 0.65 vs. AD 1.04 ml X min-1 X g-1) and to subepicardium (ENDG 0.99 vs. AD 1.83 ml X min-1 X g-1; P less than 0.05). No significant change occurred in myocardial O2 consumption (MVO2; ENDG 2.91 vs. AD 3.18 ml X min-1 X g 1), lactate extraction (ENDG = -5 vs. AD-1%), and wall thickening (WTh; ENDG + 16 vs. AD + 17%). At LAD P35, flow during ENDG was 12 but rose to 19 ml/min during AD (P less than 0.01). Flow increased to subendocardium (ENDG 0.24 vs. AD 0.46 ml X min-1 X g-1; P less than 0.02) and subepicardium (ENDG 0.51 vs. AD 0.87 ml X min-1 X g-1; P less than 0.01). No significant change occurred in MVo2 (ENDG 1.38 vs. AD 1.59 ml/min), lactate extraction (ENDG -38 vs. AD -22%), WTh (ENDG -1 vs. AD + 1%). Thus endogenous vasodilation reserve was not used fully during ischemia. AD increased flow but did not improve abnormalities in myocardial function or metabolism. PMID- 4037110 TI - End-systolic pressure-volume, pressure-length, and stress-strain relations in canine hearts. AB - End-systolic pressure-volume relationship (ESPVR) of the in situ heart in the dog was measured during changes in contractile state and was compared with end systolic pressure-length (ESPLR) or stress-strain relationship (ESSSR). Circumferential segmental length and wall thickness at the equator and external long and short axis diameters of the left ventricle (LV) were determined sonomicrometrically, and LV volume was calculated by an ellipsoidal model. Circumferential wall stress at the equator was calculated by a very thin shell model. Contractile state was enhanced by an intravenous infusion of dobutamine and was suppressed by propranolol. ESPVR, ESPLR, and ESSSR were determined during a reduction of arterial pressure by occluding temporarily the inferior caval vein (IVC). ESPVR, ESPLR, and ESSSR during changes in end-systolic pressure from 108 +/- 3 to 71 +/- 2 mmHg were linear, irrespective of inotropic states (r greater than 0.92). Slopes of these relationships increased similarly in case of dobutamine and were reduced after propranolol, yet the extrapolated X-axis intercept of ESPVR, ESPLR, and ESSSR remained unchanged. Thus the slope of ESPVR is unique to the inotropic state, and both ESPLR and ESSSR are useful as a substitute for ESPVR when there is no regional wall motion abnormality. PMID- 4037112 TI - New implanted chronic catheter device for determining blood pressure and cardiac output in conscious dog. AB - The Vascular-Access-Port (VAP) is a subcutaneous implantable device designed for repeated venous blood sampling in humans. With slight modifications the device has been used in the arterial and venous systems of dogs. This device allows for chronic repeated arterial blood pressure monitoring, monitoring of cardiac outputs, and blood sampling in conscious dogs. Infection, vascular thrombosis, and catheter extraction have not occurred. This modified VAP has been used for 6 mo and in 25 dogs to date without any failure to determine arterial blood pressure and cardiac output. PMID- 4037111 TI - Influence of buffers on dV/dtmax recovery kinetics with lidocaine in myocardium. AB - Buffers are reported to modify electrical function of heart tissue. Since electrophysiological actions of antiarrhythmic drugs are examined in different buffer systems, we set out to examine the influence of buffers on lidocaine's electrophysiological actions by measuring recovery kinetics of maximum upstroke velocity (dV/dtmax) in lidocaine solutions buffered with HCO-3-CO2, N-2 hydroxyethylpiperazine-N'-2-ethanesulfonic acid (HEPES), and tris(hydroxymethyl)aminomethane (Tris) at extracellular pH 7.4. Transmembrane potential and dV/dtmax were recorded from guinea pig papillary muscle. Recovery kinetics were determined by introducing progressively earlier test stimuli during diastole. During lidocaine (1.5 X 10(-5) M) exposure, the time constant (Tr) of dV/dtmax recovery significantly increased when 21 mM HCO-3-5% CO2 was replaced by either 5 mM HEPES (38 +/- 8%, mean, +/- SED) or 5 mM Tris (41 +/- 6%). This potentiation of Tr was 1) reversed by increasing Tris to 20 mM, and 2) also abolished by restoring HCO-3-CO2 to HEPES or Tris solutions. Decreasing HCO-3 (21 4 mM) and CO2 (5-1%) increased Tr by 27 +/- 1%. We propose that the mechanism for the potentiation of Tr is therefore related to buffer concentration rather than to the lack of HCO-3-CO2. We speculate that, by reducing surface pH, lowered buffer capacity can slow the rate of dV/dtmax recovery. PMID- 4037113 TI - Prejunctional adrenergic inhibition by aggregating platelets in canine blood vessels. AB - Experiments were performed to determine the effect of aggregating platelets on adrenergic neurotransmission. Rings of canine saphenous veins and left circumflex coronary arteries were incubated with [3H]norepinephrine and suspended for superfusion. Aggregating platelets and exogenous 5-hydroxytryptamine decreased the overflow of [3H]norepinephrine evoked by electrical stimulation of the adrenergic nerve endings. The reduction of transmitter overflow caused by 5 hydroxytryptamine was prevented by the serotonergic antagonist methiothepin in a concentration that did not significantly affect the release of 5 hydroxytryptamine or thromboxane B2 from the aggregating platelets. Methiothepin decreased but did not abolish the inhibitory effect of aggregating platelets on neurotransmitter overflow. These experiments demonstrate that 5-hydroxytryptamine and other substances released from aggregating platelets can exert prejunctional inhibition of adrenergic neurotransmission in isolated blood vessels. PMID- 4037114 TI - Differences between cytoplasmic surfaces of deep-etched heart and liver gap junctions. AB - We have compared the ultrastructures of the cytoplasmic surfaces (CS) of isolated, glutaraldehyde-fixed gap junctional pellets from rat ventricles and liver by rapid freezing on a liquid helium-cooled surface, freeze fracture, deep etching, and double-axis rotary replication (J. Microsc. Oxford 137: 121-123, 1984). Deep-etched unproteolyzed cardiac junctions [protein subunit relative molecular wt (Mr) 44,000-47,000], isolated with phenylmethylsulfonylfluoride (PMSF) [Am. J. Physiol. 246 (Heart Circ. Physiol. 15): H865-H875, 1984; C.K. Manjunath, G.E. Goings, and E. Page. Proteolysis of cardiac gap junctions during their isolation from rat hearts. J. Membr. Biol. In press.] had particulate CS, while proteolyzed cardiac junctions (subunit Mr 29,500) made without PMSF and liver junctions (Mr 28,000) made with or without PMSF had nonparticulate CS. Taken together with our previous findings that electron micrographs of thin sectioned isolated unproteolyzed cardiac junctions have urea-resistant fuzzy CS coatings [Am. J. Physiol. 246 (Heart Circ. Physiol. 15): H865-H875, 1984], that proteolyzed cardiac junctions and isolated liver junctions lack this fuzzy layer, and that the CS of in situ cardiac junctions is fuzzy [J. Membr. Biol. 78: 147 155, 1984; Am. J. Physiol. 246 (Heart Circ. Physiol 15): H865-H875, 1984], and published data that in situ freeze-etched liver gap junctions are nonparticulate (Cell 30: 395-406, 1982), these new observations strongly indicate that CS components of heart and liver gap junction proteins are structurally different. PMID- 4037115 TI - Unique coronary vasodilator induction by leukotriene D4. AB - Coronary blood flow (CBF) and myocardial contractility decrease markedly in response to intracoronary administration of leukotriene D4 (LTD4). With steady infusion, however, both CBF and contractility escape, approaching preinfusion values despite ongoing LTD4 administration. To clarify the mechanism of this escape, we reinfused plasma from the coronary vein draining the myocardial area receiving LTD4. Introducing this plasma into a coronary artery caused a marked rise in coronary flow for the duration of the plasma infusion. Coronary flow reduction with vasopressin or mechanical occlusion matching that caused by LTD4 failed to elicit vasodilator production. Thus a unique coronary vasodilator factor is induced by LTD4. Whole blood or platelet-rich plasma incubated with LTD4 in vitro produced the same pattern of coronary dilation on intracoronary infusion; LTD4 incubation with platelet-poor plasma failed to elicit a vasodilation. The vasodilator factor is stable and is not potassium, a prostaglandin, catecholamine, histamine, serotonin, adenosine, adenosine diphosphate, or platelet-activating factor. Production of this leukotriene induced vasodilator factor may account for the escape from LTD4-induced coronary constriction. PMID- 4037116 TI - Area postrema mediates tumor effects on food intake, body weight, and learned aversions. AB - Growth of a Leydig cell [LTW (m)] tumor in rats is associated with the development of significant hypophagia and severe aversions to the available diet. Lesions of the area postrema and nearby caudal medial area of the solitary tract were found to block or greatly attenuate the anorexia and food aversions that typically accompany the growth of this tumor. Thus these tumor-induced symptoms may be associated with the detection of blood-borne chemicals by cells located in or near the area postrema. PMID- 4037117 TI - Roles of right versus left vagal sensory nerves in cardiopulmonary reflexes of conscious dogs. AB - This study examined the relative roles of the right vs. left vagi in mediating the inhibitory influence of vagal sensory input on sympathetic outflow to the cardiovascular system. This objective was pursued through examination of responses to 1) interruption of tonic vagal input and 2) intracoronary administration of veratridine (Bezold-Jarisch effect). Bilateral vagal cold block (BVB) (n = 16) increased arterial pressure 25 +/- 3 mmHg and heart rate 66 +/- 7 beat/min, whereas right vagal cold block (RVB) and left vagal cold block (LVB) increased arterial pressure 13 +/- 2 and 4 +/- 2 mmHg, respectively. The relative differences in the change in mean arterial pressure were independent of heart rate since similar changes in arterial pressure were observed with preelevation of heart rate with atropine. Sinoaortic baroreceptor denervation augmented the pressure responses approximately fourfold, with the relative pressure changes produced by BVB, RVB, or LVB remaining proportionally the same. Intracoronary administration of veratridine (0.1 g/kg) produced a hypotension action (-44 +/- 6 mmHg), bradycardia (-48 +/- 8 beat/min), and a negative intropic effect (-482 +/- 68 mmHg/s, left ventricular (LV) (dP/dt)max. During RVB the depressor effect of veratridine was reduced to -18 +/- 5 mmHg, and changes in heart rate or LV (dP/dt)max were abolished. Veratridine administration during LVB decreased arterial pressure (-39 +/- 6 mmHg), heart rate (-22 +/- 6 beat/min), and LV (dP/dt)max (-250 +/- 60 mmHg). We conclude that in the conscious dog the tonic inhibitory influence of vagal afferent nerves on vasomotor outflow is predominantly associated with the right vagus as in Bezold-Jarisch effect. PMID- 4037118 TI - Platelet and plasma vasopressin in dog during hydration and vasopressin infusion. AB - Dog platelets contain a substance immunologically similar to arginine vasopressin. In conscious and anesthetized dogs under basal conditions, platelet immunoreactive vasopressin accounts for approximately 40% of the total circulating immunoreactive vasopressin. When the plasma vasopressin concentration in the anesthetized dog was lowered 75% by intravenous infusion of isotonic dextrose solution for 2 h, the platelets failed to discharge a significant quantity of immunoreactive vasopressin. Subsequently, when the plasma vasopressin concentration was elevated to a level 10-fold greater than the initial levels by intravenous infusion of arginine vasopressin, there was no statistically significant increase in the estimated platelet vasopressin content measured 1 and 2 h after the start of the infusion, although there was the suggestion that the platelets had indeed taken up some vasopressin after 2 h of vasopressin infusion. Thus immunoreactive vasopressin in dog platelets does not appear to exchange readily with plasma vasopressin. The physiological role of platelet immunoreactive vasopressin remains to be determined. PMID- 4037119 TI - Propagation of pressure pulse in kangaroo arterial system. AB - The pressure pulse contour in the ascending aorta of kangaroos is markedly different from that seen in other species, but the changes undergone by the pulse propagating along the aorta are quite similar. Alteration of wave contour and progressive amplification of the pulse in the distal aorta and peripheral arteries of other mammals have been attributed to elastic nonuniformity of the aorta and to peripheral wave reflection. In kangaroos the aorta approximates a uniform tube with essentially constant viscoelastic properties, whereas wave reflection from the lower body appears to be unusually intense and to emanate from a single functionally discrete reflecting site; this appears to be the result of arterial terminations in the muscular lower body. Intense wave reflection from the lower body is the dominant mechanism responsible for changes in the pressure pulse of kangaroos between the ascending aorta and peripheral arteries. Contour of the pulse in the ascending aorta is attributable to this and to close proximity of reflecting sites in the upper body. PMID- 4037120 TI - Neurohumoral stimulation of lipogenesis during altered states of energy balance. AB - Acid extracts of bovine hypothalamus stimulate lipogenic activity in adipose tissue. We employed a rat fat cell bioassay system to determine whether tissue concentrations of the active material vary as a function of spontaneous alterations in energy balance in hibernators and/or the obesity resulting from bilateral electrolytic lesions of the ventromedial area of the hypothalamus in rats. When hypothalamic extracts and partially purified plasma were fractionated using reverse-phase high-pressure liquid chromatography, both the void volume and material eluting 17 min after the start of a 25-min linear methanol gradient enhanced glucose incorporation into total lipid. Activities eluting with these two fractions were positively correlated with one another and were independent of insulin. The results indicate that a hypothalamic lipogenic factor (LHF) is detectable in plasma, that hypothalamic and circulating LHF concentrations vary in a reciprocal manner, and that elevations in plasma LHF concentration are associated with insulin resistance. The data suggest that the central regulation of lipogenesis is at least partially mediated by a hypothalamic humoral factor reaching fat depots via the circulation. PMID- 4037121 TI - Afferent renal nerve stimulation excites supraoptic vasopressin neurons. AB - Single-unit recording experiments were performed in pentobarbital-anesthetized rats to investigate the effects of afferent renal nerve (ARN) stimulation on the activity of neurosecretory vasopressin cells of the supraoptic nucleus (SON). Neurosecretory SON cells were identified by antidromic invasion from the neurohypophysis and classified either as vasopressin (AVP) or oxytocin (OXY) secreting on the basis of their spontaneous activity patterns and response to activation of arterial baroreceptors. Fifty-three spontaneously active units were identified bilaterally in the SON: 40 putative AVP and 13 putative OXY neurons. Most putative AVP neurons (14/14 contralateral, 18/26 ipsilateral) were excited by ARN stimulation (mean onset latency 189 +/- 5 ms, mean response duration 237 +/- 17 ms). In contrast, ARN stimulation had no effect on the firing frequency of the 13 putative OXY neurons. These data indicate that sensory information originating in the kidney selectively alters the activity of SON AVP neurons and suggest that afferent information from the kidney is important in the coordination of neural and hormonal activity concerned with body fluid balance and the regulation of arterial pressure. PMID- 4037122 TI - gamma-Aminobutyric acid concentrations are maintained in anoxic turtle brain. AB - Changes in gamma-aminobutyric acid (GABA) concentrations in the turtle (Pseudemys scripta elegans) brain were studied in situ during prolonged anoxia. With the onset of anoxia, the well-documented rapid increases in GABA found in mammalian brains were not observed in the turtle brain. Although not statistically significant, mean GABA concentrations in the turtle brain were reduced from anesthetized control values during the first 30 min of anoxia. During this initial period brain glutamate content declined. Even after 2 h of nitrogen respiration, GABA in the turtle brain still did not rise above control levels. By the 4th h of anoxia, however, GABA had increased to 147% of control values. PMID- 4037123 TI - Nycthemeral rhythms and sodium chloride appetite in rats. AB - Adrenalectomized rats maintained on a 12:12 light-dark cycle drank large amounts of 0.3 M NaCl solution during the night. They showed virtually no NaCl appetite during the day. As a result of their high day natriuresis, the adrenalectomized rats sustained a negative Na+ balance during the day about three times that of controls. This was offset by a correspondingly higher positive Na+ balance at night. In a second experiment in intact rats, the latency to exhibit NaCl appetite during polyethylene glycol-induced hypovolemia was shorter when the treatment was administered in the evening than in the morning. This again demonstrates a relative facilitation of NaCl intake at night and suggests a major nycthemeral interaction with putative physiological stimuli of NaCl appetite. PMID- 4037124 TI - A screening test for somatization disorder (hysteria). AB - For the diagnosis of somatization disorder, DSM-III requires the assessment of 37 specific symptoms, a time-consuming and cumbersome task. The authors describe a procedure by which the clinician can assess the presence of somatization disorder by screening for only seven symptoms, three of which must be present for a preliminary diagnosis of somatization disorder. The test was developed on female psychiatric outpatients (N = 85) who had multiple unexplained physical complaints beginning before the age of 30 years; it was validated on an independent sample (N = 47). The accuracy of this screening procedure is 80%-90%. PMID- 4037125 TI - Linguistic dimensions of affect and thought in somatization disorder. AB - DSM-III has established diagnostic criteria that separate somatization disorder from other overlapping symptom configurations. Nevertheless, information regarding the experience of somatization disorder is far from complete. Terms such as "masked depression" or "alexithymia" imply that a disturbance of affect is a central but guarded issue for at least some somatizing patients. Through content analysis of speech, the authors investigated the self-experience of somatization disorder in relation to affective disorder. Rather than defended depression, a distinctive characteristic found in the language of patients with somatization disorder reflects a confused, negative self-identity. PMID- 4037126 TI - Chronic pain: lifetime psychiatric diagnoses and family history. AB - Thirty-seven patients with chronic pain admitted to a 3-week inpatient pain program were interviewed using the NIMH Diagnostic Interview Schedule and the family history method. The most frequent psychiatric diagnoses were major depressive disorder (current episode = 32.4%, past episode = 43.2%) and alcohol abuse (40.5%). More than half of the patients had a history of one or more episodes of major depression and/or alcohol abuse before the onset of their chronic pain. Family history revealed that 59.5% of the patients had at least one first-degree family member with chronic pain, 29.7% had a family member with affective illness, and 37.8% had a family member with alcohol abuse. PMID- 4037128 TI - Diagnostic criteria in childhood depression. AB - Comparison of diagnoses of childhood depression from four sets of criteria (i.e., Research Diagnostic Criteria, DSM-III, and those of Poznanski and Weinberg) used with 65 children referred to a psychiatric clinic showed complete agreement in 56 (86%) of the cases. The major disagreement resulted from differences between the clinician's rating of dysphoria based on the child's nonverbal behavior and the child's and parent's verbal report of no dysphoria. Analyses of the essential symptoms of depression among the four criteria sets indicated that the nonverbal rating was most strongly associated with a diagnosis of depression and the best predictor of the severity of depression. PMID- 4037127 TI - Biopsychosocial characteristics of children who later murder: a prospective study. AB - The authors document the childhood neuropsychiatric and family characteristics of nine male subjects who were clinically evaluated as adolescents and were later arrested for murder. Those subjects are compared with 24 incarcerated delinquents who did not go on to commit violent offenses. The future murderers displayed a constellation of biopsychosocial characteristics that included psychotic symptoms, major neurological impairment, a psychotic first-degree relative, violent acts during childhood, and severe physical abuse. The authors relate this combination of factors to prediction of violence and discuss ethical issues that are involved in intervention to prevent violence. PMID- 4037130 TI - Teaching psychiatry in the health maintenance organization. AB - Psychiatric residents training in a health maintenance organization (HMO) rapidly encounter the conflict between high demand for services and limited supply of time. In one HMO setting, the Harvard Community Health Plan, supervisors assist trainees in managing their practices to recognize their avoidances and conflicts and to respond therapeutically in keeping with the setting. PMID- 4037129 TI - Sex differences in the impact of work on physical and psychological health. AB - This study examines the different impact of work on the physical and psychological health of women and men: how men and women in business and managerial professions perceive the pressures of their work environments and what the consequences (e.g., depression, anxiety, somatic complaints, and drug and alcohol abuse) of these stresses are for the individual. The results indicate significant differences between the working men and women studied in job tension, coping strain, role conflict, and health status but not in styles of coping. PMID- 4037131 TI - Preadolescent alcohol abuse and dependence. AB - The authors document 10 cases of children who met the criteria for a DSM-III axis I diagnosis of alcohol abuse or dependence by the age of 13. They present one case report to demonstrate the family history of affective disorder, especially bipolar disorder, and alcoholism that characterized these 10 patients. Most of the children with bipolar disorder responded well to psychotropics. The authors suggest that there may be a relationship between early-onset alcohol abuse and the development of major affective disorders in adolescence. PMID- 4037132 TI - Urinary free cortisol levels and dexamethasone suppression testing in organic affective disorder associated with hyperthyroidism. AB - Eleven of 32 newly diagnosed untreated patients with hyperthyroidism met DSM-III criteria for organic affective syndrome. Thirty of these patients submitted 24 hour urine specimens for measurement of urinary free cortisol levels, and 31 were given a 1-mg dexamethasone suppression test (DST) before antihyperthyroidism therapy was started. There was no difference in the mean +/- SD urinary free cortisol excretion levels between depressed and nondepressed hyperthyroid patients. One nondepressed patient demonstrated nonsuppression (greater than 5 micrograms/dl) at 8:00 a.m. These results suggest that cortisol abnormalities as reflected by urinary free cortisol levels and DST findings are uncommon in patients with hyperthyroidism whether they are depressed or nondepressed. PMID- 4037133 TI - Hematological effects of carbamazepine in patients with affective illness. AB - The hematological effects of carbamazepine, a drug effective in the acute and prophylactic treatment of manic-depressive disorder, were assessed in 43 subjects with affective disorder. Carbamazepine was found to cause statistically significant, but clinically insubstantial, decreases in white blood cell indexes. The consistent decreases in white cell counts observed with carbamazepine should be differentiated from the extremely rare, idiosyncratic blood dyscrasias reported in the literature. PMID- 4037134 TI - Effect of cocaine dependence on plasma phenylalanine and tyrosine levels and on urinary MHPG excretion. AB - Eight cocaine-dependent subjects had significantly lower urinary 3-methoxy-4 hydroxyphenylglycol excretion than did eight normal control subjects. Cocaine dependent subjects also had lower plasma tyrosine levels but not to a statistically significant degree. PMID- 4037135 TI - Sex and ethnic distribution of borderline personality disorder in an inpatient sample. AB - Among 1,583 psychiatric inpatients, fewer men than women were diagnosed as having borderline personality disorders among whites and blacks but not among Hispanics. No significant differences in the prevalence of borderline personality disorder were found among whites, blacks, and Hispanics. PMID- 4037136 TI - Plasma GABA levels in chronic alcoholics. AB - Ethanol intoxication has been noted to cause marked changes in brain and CSF levels of gamma-aminobutyric acid (GABA). Using plasma GABA levels to assess brain GABA activity, the authors found that 85 chronic alcoholics had significantly lower levels than control subjects. PMID- 4037137 TI - Nortriptyline in the treatment of a monosymptomatic delusion. PMID- 4037138 TI - Atypical panic attacks in major depression. PMID- 4037140 TI - On understanding Alzheimer's disease. PMID- 4037139 TI - Adrenoleukodystrophy and psychiatric disorder. PMID- 4037141 TI - A high-risk suicide group: the anesthesiologist involved in litigation. PMID- 4037143 TI - The insanity defense: beyond exculpation. PMID- 4037142 TI - On sinistrality and sex differences in schizophrenia. PMID- 4037144 TI - Anorexia not the same as depression. PMID- 4037145 TI - Simultaneous panic and depressive disorders. PMID- 4037146 TI - How are psychotic syndromes related to personality disorders? PMID- 4037147 TI - Spatial location judgments as a function of intention to learn, and mood state: an evaluation of an alleged automatic encoding operation. AB - An assessment of the Hasher and Zacks (1979) conceptualization of the automatic nature of the acquisition of spatial location information was made in the context of manipulations of subjects' intention to learn and mood state. The Velten (1968) mood induction procedure was used to establish depressed and nondepressed subjects. Half of each group was then presented with a matrix of geometric forms under instructions to learn the location of the forms (intentional) or to evaluate the pleasantness of the array (incidental). Subsequent tests of spatial location performance found no differences as a function of subjects' mood state, but did find a strong effect for instructional condition. The superior performance of the intentional subjects raises questions about the automatic nature of the encoding of spatial location. PMID- 4037148 TI - Blocking but not conditioned inhibition results when an added stimulus is reinforced in compound with multiple pretrained stimuli. AB - Conditioned barpress suppression by rats was used to explore the associative status of an initially neutral stimulus that was reinforced in simultaneous compound with two independently pretrained conditioned excitors. In contrast to the Rescorla-Wagner model, which predicts that the target stimulus (X) will be inhibitory following such A+/B+/ABX+ training, the present study found no evidence that X acquired inhibitory associative strength. Rather, the pretrained stimuli merely served to block conditioned excitatory responding to the target stimulus. PMID- 4037149 TI - Effect of distance instructions on size judgments. AB - The proposition that in a reduced-cue setting subjects could use cognitive information about an object's distance to make accurate judgments of its size was tested. An improved paradigm was used to determine the effects of distance instructions per se. This paradigm also allowed independent tests of the effectiveness of cue reduction. The data indicated that cue reduction was successful and that the specific distance tendency governed size judgments when there were no distance instructions. When distance instructions were given, they produced size judgments in precisely the ratio predicted by the size-distance invariance hypothesis. However, there was a large constant error, which reflects a tendency of college students to overestimate the amount of distance signified by a verbal instruction. Hence, cognitive information in the form of verbal distance instructions has precise effects on size judgments, but the latter are not veridical, even in the absence of anchor effects from the specific distance tendency and residual perceptual cues. PMID- 4037150 TI - The negative therapeutic reaction: crisis of practice or crisis of theory? PMID- 4037151 TI - The use of psychoanalytic principles in the treatment of older people. AB - In evaluating the use of psychoanalytic principles in the treatment of older people it becomes clear that, at least in some cases, treatment using the methods and philosophy of psychoanalysis can be very helpful. However, any such treatment is not effective unless it is done in conjunction with the necessary other, especially physical, treatment modalities, in an atmosphere that promotes social interaction, emotional and intellectual stimulation, and an overall environment of security and acceptance, one where the patient feels understood in his needs, desires, hopes, and fears. If we see psychoanalytic principles as a natural, healthy way of interacting, namely, of listening to the other person with patience, respect, attention, understanding, and genuine interest, then its use cannot be anything but beneficial. If we use the psychoanalytic theory and experience to gain greater insight into our patients, then this knowledge cannot be anything but contributory to the deeper understanding of their needs, desires, hopes, and fears. If we use our psychoanalytic experience to be more available as human beings to our elderly patients, then this experience cannot be anything but beneficial in providing a more satisfying and therapeutic interaction. PMID- 4037152 TI - Recent sociohistorical trends and the ascent of Kohutian "self-psychology". PMID- 4037153 TI - Shylock in "The Merchant of Venice". PMID- 4037154 TI - Going public: historical perspectives on working women. PMID- 4037155 TI - Poet, friend, and poetry: the idealized image of love in Shakespeare's sonnets. PMID- 4037156 TI - The public and the pill: is the pill making a comeback? PMID- 4037157 TI - The oral health of older Americans. PMID- 4037158 TI - Should prisoners be immunized against hepatitis B? PMID- 4037159 TI - Prevalence and trends in oral contraceptive use in premenopausal females ages 12 54 years, United States, 1971-80. AB - Data from the second National Health and Nutrition Examination Survey (NHANES II) were analyzed to estimate the prevalence of oral contraceptive use in the United States, 1976-80. The overall unadjusted prevalence of oral contraceptive use was 16.7 per cent for premenopausal females ages 12-54 years (19.2 per cent for ages 15-44 years). Approximately 8.7 million females (95 per cent confidence interval, 6.9-10.5 million) were oral contraceptive users at the midpoint of NHANES II (March 1978). Comparison to the NHANES I, conducted in 1971-74, indicated a stable number of overall oral contraceptive users in the US population during the 1970s, with shifts in certain age groups: oral contraceptive use increased for females ages 12-19 years and decreased for females ages 20-49 years. The overall age-adjusted prevalences indicated a 2 per cent (95 per cent CI, 0.2-3.8 per cent) decline in oral contraceptive use from the early to the late 1970s. The NHANES provides comparative data and supports findings from another national survey showing a decrease in the per cent of females using oral contraceptives during 1973-82. Trends in oral contraceptive use are also presented by race, poverty level, rural-urban residence, marital status, and education level. PMID- 4037160 TI - Hepatitis B in Wisconsin male prisoners: considerations for serologic screening and vaccination. AB - To develop a protocol for prevention of hepatitis B virus (HBV) transmission in Wisconsin prisons, we interviewed 619 male prisoners at incarceration to obtain information on hepatitis B risk factors. We defined previous infections by the presence of hepatitis B surface antigen (HBsAg), antibody to hepatitis B surface antigen (anti-HBs), or antibody to hepatitis B core antigen (anti-HBc). Logistic regression was used to develop a model of relative risk (RR) of HBV infection. Use of illicit intravenous (IV) drugs was the most important risk factor because of a high prevalence of IV drug use and an RR which ranged from 2.93-7.47. Other important risk factors were: prior hepatitis or jaundice (RR = 6.28), race (RR = 2.54 for Blacks, RR = 3.28 for Latinos), transfusion (RR = 3.00), and age. Previous imprisonment was not an independent risk factor for HBV, hence selective serologic screening and vaccination of prisoners are justified rather than mass screening and vaccination. Based upon prevalence of hepatitis B markers in subgroups, it is necessary to screen prisoners with prior hepatitis or jaundice, prior transfusion, and users of IV drugs. The identification of HBsAg carriers by such screening could prevent infection of "household" contacts. Users of IV drugs who are susceptible to HBV infection should be vaccinated. The remaining prisoners constitute a low-risk group for HBV infection and do not require serologic screening or vaccination. PMID- 4037161 TI - Does participation in prenatal courses lead to heavier babies? AB - In a prospective epidemiologic survey of 1,676 primiparous women delivering in four Montreal hospitals during an eight-month period, we studied the impact of prenatal courses on birthweight, maternal weight gain, and cigarette smoking. Women who participated in prenatal courses were older and of higher socioeconomic status and were less likely to be smokers than non-participants. After adjustment for these differences, newborns of course participants had similar mean birthweights compared to those of non-participants (3286 grams vs 3271 grams), and the difference for maternal weight gain was substantially reduced. Most of the reduction in cigarette consumption occurred during the first three months of pregnancy, even among later participants, suggesting that something other than prenatal courses influenced cigarette smoking reduction in course participants. We conclude that as far as the birthweight objective is concerned, the format and content of prenatal courses (as currently constituted in the Montreal region) require re-examination, and new ideas and interventions need to be developed and tested. PMID- 4037163 TI - Coital and non-coital sexual behaviors of white and black adolescents. AB - As part of a longitudinal study of young adolescents, data were collected in 1980 on the non-coital and coital sexual experiences of male and female adolescents who ranged in age from 12 to 15 at the time of the initial contact. The follow-up data were collected two years later. Both a Guttman-scale analysis and a longitudinal analysis of these data indicate different sexual patterns between White and Black teens; Whites are more likely than Blacks to engage in a predictable series of non-coital behaviors for a period of time before their first intercourse experience. Of the sexual behaviors studied, the pre-coital experiences of Black teens were less predictable and often involved only necking. These differences in sexual norms offer a partial explanation for the different pregnancy rates between these two groups. They also suggest that sexual and contraceptive education and counseling need to be cognizant of these differences since pre-coital experience may function as both a mechanism to prolong abstinence and to promote a gradual acceptance of one's sexuality. PMID- 4037162 TI - Multidisciplinary treatment of obesity with a protein-sparing modified fast: results in 668 outpatients. AB - Six hundred sixty-eight obese outpatients, 71 per cent (+/- 34) in excess of ideal weight, were enrolled in a multidisciplinary weight control program. The major components of the program included nutrition, education, behavior modification, and exercise. Rapid weight loss was accomplished using a very low calorie (less than 800 kcal) ketogenic diet. Patients adhered to the protein sparing modified fast (PSMF) for 17 +/- 12 weeks and averaged 9 +/- 17 weeks in a refeeding/maintenance program. Mean weight loss was 47 +/- 29 lb (21 +/- 13 kg) at the point of minimum weight and 41 +/- 29 lb (19 +/- 13 kg) at the end of the maintenance period. Systolic and diastolic blood pressure and serum triglycerides fell significantly in men and women. Success in weight loss was greatest in the heaviest patients, those who adhered the longest to the PSMF, and those who stayed the longest in the maintenance program. PMID- 4037164 TI - Patterns of contraceptive method of use by California family planning clinic clients, 1976-84. AB - Trends in contraceptive method of use by California family planning clients, 1976 84, are reviewed. Although use of foam and condoms doubled from 1976 to 1980 and was sustained, interest peaked but markedly declined for the diaphragm. Oral contraceptive (OC) use declined overall and most notably for older women, but there are indications in 1983 and 1984 of a slight OC "come back". Older women were more likely to choose methods free from medical side effects than were younger women. PMID- 4037166 TI - Assessment of salt use at the table: comparison of observed and reported behavior. AB - Observations were made of salt added during meals. Nineteen per cent of 211 participants salted before tasting food, 18 per cent salted after tasting, and 2 per cent salted both before and after tasting. Of those who self-reported "never" to salt food before tasting, 6 per cent were observed to do so. Of those who reported never to salt after tasting, 3 per cent did so. Results support the conclusion that self-reported abstinence from use of table salt is strongly correlated with actual behavior. PMID- 4037165 TI - Incidence of hepatitis B in the penitentiary of New Mexico. AB - A study was conducted to determine the incidence of hepatitis B (HB) in a prison population. Forty-seven per cent of 455 male prisoners had evidence of past HB infection. HB seropositivity was most strongly correlated with: 1) a history of IV drug abuse; 2) age; 3) total time in any prison; and 4) race. During a one year study period there were no clinical cases of HB in the prison and the seroconversion rate was 0.8 per cent among prisoners still incarcerated. PMID- 4037167 TI - Self-reported pelvic inflammatory disease in the US: a common occurrence. AB - Based on a nationally representative sample of American women of reproductive age, in 1982, one in seven reported having had pelvic inflammatory disease (PID). One in ten had received ambulatory care, and one in 25 were hospitalized for PID. A two-fold race differential was observed in self-reported history of PID. One in four Blacks compared to one in eight Whites reported having received treatment for this condition sometime in the past. The previous history of PID, especially in the older age groups, reflects the combined effect of secular trends in PID incidence and temporal changes in diagnostic and treatment practices. PMID- 4037168 TI - Self-management education of children with asthma: AIR WISE. AB - This study was conducted to test the efficacy of AIR WISE, an individually administered asthma self-management program. Subjects were paired and randomly assigned to either an experimental group (N = 7) or a control group (N = 7). The frequency of experimental group emergency visits, analyzed over a 12-month posttreatment period, was substantially less than those of the control group, supporting the hypothesis that AIR WISE is effective in high-utilizer children through improved self-management. PMID- 4037169 TI - Correlates of depressive symptoms among a select population of black men. AB - This study was undertaken to provide information on the impact of demographic factors, stressful life events, and sociocultural patterns on depressive symptomatology among 142 noninstitutionalized Black men. The findings indicate that age, family income, household size, employment status, and conflict between the sexes were related to the presence of depressive symptoms. When controls were introduced, only family income and conflict between the sexes were correlates of depressive symptoms among Black men in this study. PMID- 4037170 TI - Dog and cat ownership among suicides and matched controls. AB - In Washington County, Maryland, ownership of cats and/or dogs was compared among 48 residents who committed suicide in the years 1975-83 and 96 living controls matched to the suicides by race, sex, and date of birth. Another comparison used as controls persons of same race, sex, and age who died of causes other than suicide in the same year as the suicide. No material association between pet ownership and suicide was observed. PMID- 4037171 TI - On risks, costs of sterilization. PMID- 4037172 TI - Biochemical studies of human placental microvillous plasma membrane proteins. AB - Isolated human syncytiotrophoblast microvillous plasma membranes (StMPM) have been examined by electron microscopy, SDS-polyacrylamide gel electrophoresis (SDS PAGE), two-dimensional PAGE (2D-PAGE), and immunoblots. Electron microscopy of StMPM pellets revealed populations of membrane-bounded vesicles that disrupted after treatment with the chaotrope 3M KCl for 16 hr; with increasing molarity of another chaotrope (NH4SCN), the vesicles became smaller and more homogeneous. NH4SCN treatment resulted in significant reduction on SDS and 2D-PAGE analysis of only one protein at 80kd, shown by immunoblotting to be transferrin; 3M KCl had little effect and appeared to be a poor chaotrope. Chromogenic silver staining of SDS-PAGE gels demonstrated over 50 StMPM-associated discrete protein components. Immunoblotting revealed transferrin (80kd), albumin (65kd), IgG heavy chain (56kd), and Gc protein (56kd). Alpha-2-macroglobulin (alpha 2M) was identified at 180kd and 95kd; the smaller component may be a proteolytic derivative indicating alpha 2M binding to a trophoblast surface protease. Numerous discrete protein dots, and groups of dots characteristic of charge heterogeneity of individual proteins, were observed on high resolution 2D-PAGE. The most intensely stained proteins were transferrin (80kd), albumin (65kd), placental-type alkaline phosphatase (66kd), and actin (46kd). This 2D-PAGE technique is a superior method for analyzing the trophoblast membrane proteins, and the system described will enable systematic mapping of these components. PMID- 4037173 TI - On the immunogenicity of the beta subunit of ovine luteinizing hormone (oLH beta) and equine chorionic gonadotropin (eCG) in the chimpanzee (Pan troglodytes): effect of antiserum on monkey cycle and early pregnancy. AB - Antibody to ovine LH beta (oLH beta) subunit and equine chorionic gonadotropin (eCG) were produced in adult male chimpanzees and evaluated for cross reactivity with oLH, human chorionic gonadotropin (hCG) and eCG by in vitro and in vivo methods. Chimpanzee antiserum to eCG failed to cross-react with hCG, but antibody raised against oLH beta subunit effectively neutralized not only exogenously administered hCG but also endogenous pituitary LH and monkey (Macaca radiata) chorionic gonadotropin. Chimpanzee antiserum to oLH beta when administered early in pregnancy reduced progesterone levels and terminated gestation in bonnet monkeys. Our data suggest that active immunization of chimpanzee, an ape that is very close to human, with oLH beta subunit leads to production of antibodies that are likely to affect both normal cycle as well as pregnancy. PMID- 4037174 TI - In vitro fertilization results for women with sperm antibodies in plasma and follicular fluid. AB - In vitro fertilization (IVF) and embryo transfer results were analyzed for three women with sperm antibodies in their plasma and follicular fluid. These preliminary results suggest that substitution of the patients' serum by replacement serum in the fertilization and embryo growth media may prove to be an effective means of improving IVF treatment for women with sperm immunity. PMID- 4037175 TI - A human sperm coating antigen isolated from sperm cell membrane. AB - A human sperm cell membrane antigen that is highly specific to sperm and seminal plasma was isolated from plasma membrane fraction of spermatozoa using rabbit antiserum against human seminal plasma. In addition to the high specificity to sperm and seminal plasma, the isolated antigen showed the following characteristics: (1) It is a glycoprotein of approximately 12,000 daltons that has an affinity to lentil lectin; (2) it is distributed in human milk other than in sperm and seminal plasma, but is not found in any other organs and tissues including testis; (3) seminal plasma contains the largest amount of the antigen activity, 60-fold greater than spermatozoa and 900-fold greater than milk, suggesting that this antigen could be a sperm-coating seminal plasma antigen. PMID- 4037176 TI - Effect of maternal parasitic disease on the neonate. AB - Parasitic disease is the most common infectious disease complication of pregnancy worldwide, resulting in maternal debilitation and fetal prematurity and low birth weight. The increasing incidence of these diseases in our population led to the present study of 125 patients, 34 of whom were found to be infected with at least one intestinal parasite. In contrast to studies in developing countries, no significant differences in either maternal anemia, or fetal birth weight, or prematurity were found between the infected and non-infected groups. However, there was a three-fold increase in the incidence of significant neonatal hyperbilirubinemia in the parasitized group. Parasitic disease complicating pregnancy in our population does not appear to exert the same adverse effect on mother and fetus as that described in other countries. In view of the limited pathology associated with parasitic disease, treatment, other than with iron and vitamin supplementation, is not routinely indicated in pregnancy in populations similar to ours. However, due to the increased incidence of neonatal jaundice and morbidity we would recommend close observation of the neonates in the immediate postpartum period. PMID- 4037177 TI - The interaction of Leishmania donovani promastigotes and human fibroblasts in vitro. AB - Leishmania donovani promastigotes derived from infected hamster spleens, in either log phase or stationary phase growth, associated with human foreskin fibroblasts in vitro and assumed the morphological characteristics of amastigotes. This apparent conversion was noted within hours at 26 degrees C, 32 degrees C or 37 degrees C; in the continued presence of promastigotes, increasing numbers of amastigote-like forms were seen for 2 weeks at 26 degrees C or 32 degrees C. At 37 degrees C amastigote-like forms declined sharply after 6 days. Multiplication of amastigote-like forms was not observed at any temperature, this was also true of freshly isolated amastigotes from hamster spleens which associated with fibroblasts but did not multiply. Approximately 0.1% of promastigotes appeared to convert per day. Amastigote-like forms were seen within fibroblasts by transmission electron microscopy, surrounded by a closely applied host membrane. Scanning electron microscopy showed promastigotes with their flagellae under or within fibroblasts, but phagocytosis was not observed. These experiments suggest that the conditions required for promastigote-to-amastigote conversion may be different than those required for amastigote multiplication, and the mammalian core body temperature may not be required for promastigote conversion. PMID- 4037179 TI - A Schistosoma mansoni surface glycoprotein cross-reactive with a T1 antigen of Fasciola hepatica. AB - An antigen recognized by monoclonal antibody 306B3/5 and present on the surface of S. mansoni was expressed by F. hepatica in the pattern typical of T1 antigens. A single polypeptide of molecular weight (Mr) 160,000 was precipitated from metabolically labeled concanavalin A-binding F. hepatica glycoproteins, whereas multiple polypeptides ranging from Mr greater than 200,000 to Mr 45,000 were precipitated from metabolically labeled glycoproteins of male S. mansoni. The polypeptides of both species were also precipitated by sera of infected hosts, and may account for some of the serological cross-reactivity between S. mansoni and F. hepatica in immunodiagnostic assays. These antigens may also represent potentially immunoprophylactic reagents. PMID- 4037178 TI - Identification and characterization of a major Schistosoma mansoni glycoprotein antigen cross-reactive with Fasciola hepatica. AB - A major surface antigen of Schistosoma mansoni has been identified and characterized as a glycoprotein of 66,000 molecular weight (Mr) and isoelectric point of 6.2-6.1 (SM66-GP) by use of a monoclonal antibody. The antigen was expressed by schistosome eggs, cercariae, larvae, and adults, and was recognized by sera of schistosome infected hosts. Direct immunofluorescence microscopy showed the antigen was distributed in a uniform pattern on the entire worm surface. Indirect immunofluorescence microscopy revealed that it was present in the parenchymal tissue of immature and mature Fasciola hepatica, in the gut of the mature fluke, and in embryonated fasciola eggs. The cross-reactive F. hepatica epitope recognized was expressed on a polypeptide of Mr 220,000. PMID- 4037180 TI - Vascular changes in cerebral schistosomiasis mansoni: a histopathological study of fifteen cases. AB - A histopathological study of 15 cases of cerebral schistosomiasis mansoni is presented. All patients had the hepatosplenic form, and except for two, the cardiopulmonary form of the disease. The most common lesions were periovular mononuclear inflammatory reaction, granulomas and focal astrocytosis. Arteritis and vascular lesions suggesting sequelae of arteritis or ova passage through the arterial wall were found in 26.7% and 20% of the cases, respectively. The clinical features and the possible mechanisms by which the S. mansoni ova produce the vascular changes are discussed. These findings indicate that vascular changes were common in our patients with cerebral schistosomiasis mansoni. PMID- 4037182 TI - Macracanthorhynchus ingens from a child in Texas. AB - Nine acanthocephala recovered over a two-month period from the stools of a 10 month-old child in Texas were identified as Macracanthorhynchus ingens, a common intestinal parasite of the raccoon, Procyon lotor. PMID- 4037181 TI - Incidence of endemic Opisthorchis viverrini infection in a village in northeast Thailand. AB - Incidence, measured as the proportion of persons whose stools become positive within one year, was studied in endemic Opisthorchis viverrini, the human liver fluke, in a northeastern Thai village over a two-year period. Incidence was higher in males than in females, especially in children under five years of age. It was at least 47% overall in the first year of the study, but declined to below 20% per year in the second. This is attributed to drying of a local water reservoir and decline in availability of infective stages in fish. The fluctuation of incidence is probably due to the large variations in rainfall from year to year. The rate of reversion from positive to negative varied from 2% to 6% per year. PMID- 4037183 TI - The childhood health effects of an improved water supply system on a remote Panamanian island. AB - The incidence of diarrhea, respiratory disease, and skin infections was prospectively determined after the introduction of a system which distributed unlimited quantities of high quality fresh water to each of the 150 housing units on Tupile, an island devoid of fresh water located off Panama's Caribbean coast and inhabited by 1,500 Cuna Indians. Tupile residents used 7.1 liters of water/person/day compared to the 2.3 usage rate of inhabitants on Achutupo, the control island. Despite ready availability of water in each household, Tupile residents continued to store water in contaminated vessels prior to use. Forty percent of stored water samples tested on Tupile and 45% on Achutupo were contaminated with E. coli organisms. There were 4.7 episodes/child year (E/Y) of acute diarrhea on Tupile compared with the 3.5 rate on Achutupo. The rotavirus infection rate on Tupile was 0.8 E/Y compared with 0.2 E/Y on Achutupo. Infection rates for Norwalk virus, respiratory syncytial virus and Coxsackie B 1-6 viruses were similar on both islands. Respiratory disease rates were high on both islands (2.2 E/Y on Tupile, 2.7 E/Y on Achutupo). Achutupo had much higher rates of impetigo and scabies (0.6 E/Y and 2.5 E/Y, respectively) than Tupile (0.2 E/Y and 1.4 E/Y). Provision of the water distribution system had a beneficial effect on the incidence of water-washed diseases (impetigo and scabies), but at best had no effect on diarrheal disease. PMID- 4037184 TI - Arbovirus investigations in Argentina, 1977-1980. I. Historical aspects and description of study sites. AB - This is the introductory paper to a series on the ecology of arboviruses in Argentina. Epizootics of equine encephalitis have occurred since at least 1908, principally in the Pampa and Espinal biogeographic zones, with significant economic losses; human cases of encephalitis have been rare or absent. Both western equine and eastern equine encephalitis viruses have been isolated from horses during these epizootics, but the mosquitoes responsible for transmission have not been identified. A number of isolations of Venezuelan equine encephalitis (VEE) virus were reported between 1936 and 1958 in Argentina, but the validity of these findings has been seriously questioned. Nevertheless, serological evidence exists for human infections with a member of the VEE virus complex. Serological surveys conducted in the 1960s indicate a high prevalence of infection of humans and domestic animals with St. Louis encephalitis (SLE), and 2 SLE virus strains have been isolated from rodents. Human disease, however, has rarely been associated with SLE infection. Only 7 isolations of other arboviruses have been described (3 of Maguari, 1 of Aura, 2 of Una, and 1 of an untyped Bunyamwera group virus). In 1977, we began longitudinal field studies in Santa Fe Province, the epicenter of previous equine epizootics, and in 1980 we extended these studies to Chaco and Corrientes provinces. The study sites are described in this paper. PMID- 4037185 TI - Homogeneity among Senegalese strains of yellow fever virus. AB - A series of 16 yellow fever (YF) viruses isolated from mosquitoes, monkeys and humans in different epidemiological contexts in Senegal and The Gambia between 1976 and 1983, was analyzed by T1 RNase oligonucleotide fingerprints of the genomic 32P-labeled RNA, by SDS-polyacrylamide gel electrophoresis of the intracellular virus-specified polypeptides, by peptide mapping of the envelope E glycoprotein and by immunological reactivities with monoclonal antibody fluids (MAF's) against the E glycoprotein. These strains had not been passed in suckling mice and were isolated in Aedes pseudoscutellaris Mos 61 cultured cells. These strains showed no virulence in three-week-old Swiss mice when injected intraperitoneally. Direct comparison of the large T1 RNase-resistant oligonucleotide maps indicated a relative genetic stability (92%-100%). A greater change was observed when these strains were compared with an epidemic YF strain isolated in 1965 with an oligonucleotide fingerprint map sharing 82%-88% similarity. The YF-specified proteins were identical in their molecular weight, and the fragments obtained after limited proteolysis of the envelope protein using protease V8 or alphachymotrypsine indicated that the strains were chemically similar. Only a few differences were observed when the strains were seroneutralized with MAF's, but no relation could be made with genetic or biological data. This suggested that the YF virus strains isolated from the same geographic area and during a short period of time had evolved slowly. Moreover, all the viruses were closely related and no correlation could be established with the apparent variations in virulence in nature. PMID- 4037186 TI - Oral infection and transmission of La Crosse virus by an enzootic strain of Aedes triseriatus feeding on chipmunks with a range of viremia levels. AB - The susceptibility of Aedes triseriatus to oral infection with La Crosse (LAC) virus resulting from feeding on chipmunks with viremia titers of 0.6 to 4.6 log10SMICLD50/0.025 ml was determined. Results indicated that viremia titers must exceed 3.2 log10SMICLD50/0.025 ml before a significant proportion (greater than or equal to 50%) of mosquitoes are infected and capable of transmitting LAC virus. Mosquitoes which fed on chipmunk blood-LAC virus mixtures through a membrane feeder had significantly lower infection rates at virus titers of 1.8 to 4.4 log10SMICLD50/0.025 ml and transmission was also significantly reduced. Application of these data to LAC viremia titers measured in chipmunks in an earlier study indicate that viremias sufficiently high to ensure transmission by the mosquitoes becoming orally infected average only about 1 day per infective bite delivered to the susceptible portion of the amplifier population. Oral infection and transmission rates were also determined for Ae. triseriatus feeding on chipmunk blood containing LAC virus neutralizing (N) antibodies and for Ae. triseriatus feeding on deer blood containing Jamestown Canyon (JC) virus N antibodies. Infection rates were similar to those observed in mosquitoes imbibing blood free of N antibody at the virus titers tested, but, oral transmission was reduced in females feeding on chipmunk blood-LAC virus mixtures containing LAC N antibodies and there was no transmission by females feeding on deer blood-LAC virus mixtures containing JC N antibodies. These data suggest that high LAC antibody prevalences in chipmunk populations and high LAC or JC antibody prevalences in deer populations may be antagonistic to horizontal LAC virus transmission. PMID- 4037188 TI - Selection of surgical chairmen. PMID- 4037187 TI - Kinetic study of platelets and fibrinogen in Lassa virus-infected monkeys and early pathologic events in Mopeia virus-infected monkeys. AB - The rhesus monkey, an established model of Lassa fever, was used to study hematologic and hemostatic aspects of Lassa fever and whether Mopeia (also known as Mozambique) virus induces any cellular damage in this model. Six days after subcutaneous injection of 10(3.48) plaque forming units (PFU) of Lassa virus (Josiah strain) one group of monkeys received an intravenous injection of 111In labeled allogeneic platelets and another group received 125I-labeled alogeneic fibrinogen. Lassa virus-infected monkeys developed a severe clinical illness with high viremia and typical pathology. Lassa antigen was found in most tissues using a Lassa nucleocapsid-specific monoclonal antibody. Platelet counts remained within normal limits. Platelet and fibrinogen kinetics were similar in infected and control animals. Hematologic and hemostatic changes indicate that disseminated intravascular coagulation plays no role in this model of Lassa fever. Levels of plasma fibronectin were reduced in Lassa-infected monkeys. Mopeia virus-infected monkeys were normothemic, aviremic, and there was no detection of Mopeia antigen in any tissues using polyclonal or monoclonal antibodies. Mopeia virus was recovered from the spleen of one monkey. Mopeia virus was associated with hepatocellular and renal tubular damage. PMID- 4037189 TI - Prognostic significance of the absolute lymphocyte count in acute pancreatitis. AB - The absolute lymphocyte count was calculated with 48 hours of admission in 154 patients with acute pancreatitis. Twenty-three patients had severe pancreatitis and 131 patients had mild pancreatitis. The mean absolute lymphocyte count for the severe group was 880 +/- 102 cells/mm3 and for the mild group, 1,115 +/- 116 cells/mm3. The absolute lymphocyte count accurately predicted 78 percent of the severe attacks and 86 percent of the mild attacks. PMID- 4037190 TI - Evaluation of possible patient survival in a mock airplane disaster. AB - A mock disaster at Orange County's John Wayne Airport provided a basis for examining correct triage of patients and their arrival time for definitive care. The ability to triage critically injured patients in a timely fashion was found to be only slightly better than chance routing. For most of the seriously and critically injured patients, it took more than 1.5 hours to reach the hospital. Advanced life support with intravenous fluid resuscitation available on the scene would probably reduce the mortality of possible disaster victims by 50 percent. These problems are presently being addressed. In future disaster exercises, the present type of evaluation could be used to judge improvement in possible patient triage and survival. PMID- 4037191 TI - Long-term disability associated with flail chest injury. AB - Twenty-two trauma victims who had sustained flail chest as their only significant injury were evaluated to determine the final outcome. Fourteen patients (63.9 percent) were found to have long-term sequelae. The most common long-term problems after flail chest injury were persistent chest wall pain, chest wall deformity, and dyspnea on exertion. Five patients (22 percent) remained disabled in varying degrees. PMID- 4037192 TI - Secretion of beta-lactam antibiotics in pure human pancreatic juice. AB - The secretion of cephalothin and cefoxitin in stimulated pure pancreatic juice was studied in 13 persons after intravenous administration of antibiotics. Of all these studied, three had acute relapsing pancreatitis, five chronic pancreatitis, and five were control subjects. Antibiotic levels were measured in paired pure pancreatic juice and serum samples at fixed time intervals after administration. Cephalothin was detected in very low levels (1 to 1.8 micrograms/ml) in the pure pancreatic juice of four of the six persons studied (3 micrograms/ml). Although therapeutic levels were not obtained in stimulated pure pancreatic juice with either antibiotic, additional studies evaluating antibiotic levels in unstimulated pure pancreatic juice and in pancreatic tissue would be helpful in assessing the role of antibiotic therapy in the treatment of pancreatitis. PMID- 4037193 TI - Recurrence after parietal cell vagotomy for peptic ulcer disease. AB - The value of parietal cell vagotomy as a safe surgical procedure in the treatment of chronic peptic ulcer disease has been seemingly limited by the high recurrence rate usually reported. In this 10 year experience of 405 consecutive parietal cell vagotomy operations, 57 patients with recurrent ulceration were evaluated to try to answer the questions of where and why recurrent ulceration appears and how to treat it. Patients with pyloric or prepyloric ulcer disease had recurrence of disease earlier than did patients with chronic duodenal ulcer disease. Consequently, pyloric or prepyloric ulcer patients had a higher recurrence rate in the early postoperative period than chronic duodenal ulcer patients, but this difference disappeared after the seventh postoperative year. Patients with recurrent chronic duodenal ulcer disease have high postoperative acid secretion levels, indicating incomplete vagotomy as a causative factor. Patients with recurrent pyloric or prepyloric ulcer disease have postoperative acid secretion similar to that of patients without recurrence, suggesting another etiologic factor. Thirty of 57 patients with recurrent ulcer had successful medical treatment. A conservative attitude towards recurrences is justified, particularly when symptoms are few and the postoperative acid secretion tests indicate complete or partial vagotomy. Surgical therapy consisting of truncal vagotomy and pyloroplasty in cases of incomplete vagotomy and antrectomy in cases of complete vagotomy should be reserved for patients with symptoms and a disease course that cannot be controlled by conservative treatment. PMID- 4037194 TI - The preoperative angiogram as a predictor of peripheral vascular runoff. AB - The preoperative angiogram is widely used as a means of assessing peripheral vascular runoff before bypass grafting, but the correlation between preoperative angiographic findings and actual measurements of peripheral vascular resistance has not been adequately examined. To test this correlation, we first devised a simple technique for measuring peripheral resistance and validated it in five dogs. Increases in peripheral resistance were artificially produced by temporarily occluding either the deep or superficial femoral artery or by intravenous administration of phenylephrine hydrochloride, a vasoconstrictor. In each instance, significant increases in resistance could be measured. We then used a similar technique to measure resistance in 23 patients undergoing peripheral bypass surgery. In addition, preoperative angiograms for these 23 patients were independently scored by four readers as 0, 1, 2, or 3 based on the number of patent vessels seen below the knee. Variations in scoring from reader to reader suggested that the present criteria for grading angiograms on this basis are unclear. Moreover, the correlation between angiographic score and measured resistance was poor for three of the four scorers (-0.21 to -0.29, p greater than 0.05). The angiographic scores of one reader, however, correlated reasonably well with the peripheral resistance measured at surgery (-0.59, p = 0.01). These findings demonstrate that current criteria for grading the preoperative angiogram are not sufficiently standardized to reliably predict runoff from a preoperative angiogram. However, these findings also suggest that it may be possible to identify angiographic findings that correlate well with changes in measured resistance. PMID- 4037195 TI - Femoral hernia. Review of 2,105 repairs in a 17 year period. AB - A series of 2,105 femoral hernia repairs performed in a 17 year period has been reviewed. Of these, 1,138 were primary and 967 were recurrent. In the majority of the primary repairs (730 in men and 408 in women), a low or subinguinal approach was used. There was often an ipsilateral inguinal hernia, particularly in men, that required a separate simultaneous routine repair. An overall recurrence rate of approximately 2 percent was achieved in the primary group. Of the recurrent repairs, 778 were in men and 189 in women. The subinguinal approach was favored in the majority of these patients also. The rerecurrence rate was approximately 10 percent in men and 7 percent in women. Despite this, the low approach has still often been considered the best. These recurrent repairs are frequently difficult to treat. A strategy for the treatment of the larger and the more difficult recurrent femoral hernias has been suggested herein. PMID- 4037196 TI - Abdominal wall and inguinal hernias in continuous ambulatory peritoneal dialysis patients. AB - This retrospective analysis of 140 continuous ambulatory peritoneal dialysis patients followed during a 4 year period revealed a 5 percent incidence of abdominal wall hernias. Inguinal hernias were frequently manifested as unilateral scrotal swelling. Hernias too small to be appreciated by physical examination were easily demonstrable with intraperitoneal instillation of technetium 99m sulfur colloid through the continuous ambulatory peritoneal dialysis catheter. This procedure was also useful when differentiating dialysate leaks from inguinal hernia in the early and late postoperative periods. Recurrences developed in 27 percent of the herniorrhaphies. Factors contributing to the development of abdominal wall hernias in continuous ambulatory peritoneal dialysis patients include uremia, obesity, anemia, and chronically elevated intraperitoneal pressures. PMID- 4037197 TI - Changes in bile salt composition after cholecystectomy and ileal resection. AB - The effect of ileal resection and cholecystectomy on bile salt metabolism was studied in female prairie dogs 4 weeks after either a sham laparotomy, cholecystectomy, ileal resection, or cholecystectomy and ileal resection. Bile was collected from a common bile duct cannula at hourly intervals for 12 hours. Pool sizes and synthetic rates of primary and secondary bile salts were determined from washout curves. Cholate, chenodeoxycholate, deoxycholate, and lithocholate levels were determined by gas chromatography from pooled collections of bile. After cholecystectomy and ileal resection, the pool sizes of primary and secondary bile salts were significantly reduced to amounts that were much less than the pool sizes after either procedure alone. Primary bile salt synthesis was significantly increased after combined cholecystectomy and ileal resection, to the same degree as cholecystectomy alone. After the combined procedures, there was a decrease in the proportion of cholate in hepatic bile associated with an increase in chenodeoxycholate, deoxycholate, and lithocholate levels. The data suggest that after the loss of both ileum and gallbladder the bile salt pool sizes are drastically reduced, the synthesis of primary bile salts is increased, and the proportion of secondary bile salts is increased. Cholecystectomy should be avoided, if possible, in patients with ileal resection in order to conserve the bile salt pool and prevent severe fat malabsorption. PMID- 4037198 TI - Adenocarcinoma in columnar-lined Barrett's esophagus. Analysis of 13 esophagectomies. AB - From 1977 to 1982, 13 patients with adenocarcinoma arising in the distal esophagus lined by columnar epithelium underwent esophagectomy with detailed analysis of the pathologic specimen. In three patients, microinvasive carcinoma was detected before dysplasia occurred. In five patients, the ectopic mucosa was discontinuous, prolonged cranially by islands of columnar epithelium scattered in the squamous mucosa. Variable degrees of dysplasia were found in the columnar epithelium in seven specimens in areas of intestinal metaplasia. In four patients with high-grade dysplasia, several foci of intramucosal carcinoma were identified. They were scattered over the whole length of the ectopic mucosa. These data strongly suggest that adenocarcinoma develops from dysplasia, the real premalignant lesion. Careful periodic screening must be carried out in patients identified as having Barrett's esophagus. Dysplasia may be detected and located by endoscopy with dye spraying with directed biopsies. Patients with high-grade dysplasia should undergo esophagectomy with resection of the whole ectopic mucosa because they are at high risk for development of carcinoma. PMID- 4037199 TI - Malignant tumors of the anus. A study of 106 cases. AB - This study of 106 cases of malignant tumors of the anus has shown that the diagnosis was often made late. In 15 percent of the patients the tumor was at the anal margin; in 61 percent, in the anal canal, and in 24 percent, the tumor was so extensive that its origin could not be determined clinically. In nearly half of the cases, the cancers were advanced and showed perirectal metastases. Surgical treatment was the rule, with local excision for carcinomas of the anal margin and abdominoperineal resection for tumors of the canal. The general prognosis over a period of several decades remains poor. We found a 20 percent 5 year survival rate for epidermoid carcinoma of the anal canal, excluding deaths from causes other than cancer during the follow-up period. PMID- 4037200 TI - Sacrococcygeal teratomas in infants and children. AB - From 1941 through 1983, a total of 66 patients with sacrococcygeal teratoma were seen, representing 41 percent of the total of 162 patients with teratomas from all anatomic sites seen over this period. Forty-six (70 percent) of the patients with sacrococcygeal teratomas were female and 34 (52 percent) were neonates. Younger patients had a significantly better prognosis. Approximately half (48 percent) of the patients had benign tumors. Of the other 34 patients, 19 (29 percent) had frank malignancy, being either a purely malignant tumor or a tumor with malignant mixed with benign elements, and 15 (23 percent) patients had tumors containing embryonic but no malignant components. Patients with tumors containing mature adult or embryonic tissues have a good prognosis. However, malignant sacrococcygeal teratoma portends a bleak prognosis irrespective of therapy (in this series only one patient survived among 19 patients with an average survival of 16 months after diagnosis). PMID- 4037201 TI - Management of retroperitoneal sarcomas and patient survival. AB - Sixty-eight patients with retroperitoneal sarcomas had an estimated 5 year survival rate of 34 percent after initial treatment. Patients with complete resection of the tumor had a 5 year rate of 64 percent and a 7 year rate of 56 percent. The respective survival rates for patients with partial excision were 33 percent and 0 and for those with only a biopsy the survival rates at 5 and 7 years were 10 percent. Radiotherapy with chemotherapy or chemotherapy alone was given to 47 patients. In the treatment of macroscopic tumor, radiotherapy or radiotherapy plus chemotherapy resulted in a 5 year survival rate of 10 percent and chemotherapy alone in a 5 year survival rate of 8 percent. Complete surgical resection is an important part of the management of retroperitoneal sarcomas and, with modern techniques of exposure, should be possible in the majority of patients. PMID- 4037202 TI - Lactomer copolymer absorbable staples in gastrointestinal surgery. AB - We performed a series of experimental studies to determine the clinical feasibility of using lactomer copolymer absorbable staples in gastrointestinal surgery. The stapling properties, reliability of suture and wound healing, and degree of inflammatory response were compared to similar properties of standard metal staples and polyglactin sutures. The absorbable staples were used in partial gastric transection, Billroth II gastrojejunostomy, and to close the ileum and ascending colon as part of an ileocecal resection. There were no deaths or complications in the nine experimental animals. At sacrifice 2 and 4 weeks after operation, the absorbable staples were intact with little or no macroscopic or microscopic evidence of absorption. The mucosal and submucosal layers were completely healed at 2 weeks, but muscular and serosal layers, although in excellent approximation, were incompletely joined. Inflammatory reactions around the lactomer staples and polyglactin sutures were comparable, but greater than that observed around metal staples. The studies suggest that staple techniques using absorbable materials are feasible and safe in gastrointestinal surgery. PMID- 4037203 TI - Gluteal thigh flap repair of chronic perineal wounds. AB - Since the introduction of the gluteal thigh flap in 1979, we have had the opportunity to study and modify this reconstructive technique in over 40 patients. Our successful experience with the gluteal thigh flap in six consecutive patients with difficult, nonhealing perineal pelvic sinuses has increased our confidence with this modality and led to a modified technique. Bilateral deepithelialized and well-vascularized flaps are harvested from the posterior thighs and transferred to the perineal wounds on pliable musculofascial pedicles through the ischiorectal space. Proper filling of the pelvic space requires adequate debridement, which may include release of a bottleneck narrowing of the sacral promontory. Donor site morbidity is minimal and temporary. Follow-up periods of 8 months to 5 years have revealed no wound recurrence. PMID- 4037204 TI - Gastropleural fistula. Report of three cases and review of the literature. AB - Three cases of gastropleural fistulas of different causes are presented. Patients with acute fistulas from ruptured intrathoracic portions of stomach appear to benefit from early surgery and repair. The management of more insidious gastropleural fistulas probably demands a more conservative approach. PMID- 4037205 TI - Effects of head gamma-irradiation and anesthesia on serum corticosterone and thyroid hormones in the rat. PMID- 4037206 TI - The effects of hypolipidaemic benzodiazepines on serum lipoproteins in hyperlipidaemic rats. PMID- 4037208 TI - [Elements of a reformation of living taxonomy]. PMID- 4037207 TI - [Hemodynamic effects of naloxone in brain death (preliminary results)]. PMID- 4037209 TI - Modification of urinary potassium secretion following lithium in rats of different ages. PMID- 4037210 TI - Changes in thyrotropic hormone, triiodothyronine and thyroxine level in endotoxin shock in rats. PMID- 4037211 TI - [Use of Gamma-OH by the oral route in children]. PMID- 4037212 TI - [Problems posed by anesthesia for surgery of the posterior fossa]. PMID- 4037213 TI - [Functional anatomy of the posterior fossa]. PMID- 4037214 TI - [Central control of respiration]. PMID- 4037215 TI - [Etiology and prevention of cardiovascular disorders in surgery of the posterior cerebral fossae in the sitting position]. PMID- 4037216 TI - [Effects of the ventral decubitus position on hemodynamic parameters]. PMID- 4037217 TI - [Surgery of the posterior cerebral fossa in a sitting position in children less than 1 year old: installation and anesthesia]. PMID- 4037218 TI - [Early postoperative period in surgery of the posterior cerebral fossa in infants and children, in the sitting position]. PMID- 4037219 TI - [Value of evoked brain stem potentials in hydrocephalus caused by tumor of the posterior fossa (preliminary study)]. PMID- 4037220 TI - [Per- and postoperative complications of surgery of acoustic neurinomas]. PMID- 4037221 TI - [Anomalies of the respiratory control system in surgery of acoustic neurinomas]. PMID- 4037222 TI - [Postoperative complications of acoustic neurinoma surgery by the posterior fossa: apropos of 60 cases]. PMID- 4037223 TI - [A case of paradoxical gas embolism]. PMID- 4037224 TI - [Elements of a reformation of living taxonomy. II. The great taxa]. PMID- 4037225 TI - Evaluation of the interrelations between muscular and cardiovascular responses using autoregressive models. PMID- 4037226 TI - Acute bilateral sequential vestibular neuritis. AB - Two cases of bilateral sequential vestibular neuritis demonstrate the significant persistent disequilibrium that follows involvement of the second ear. The etiology for the loss of vestibular function is postulated to be a viral neuritis. Vestibular suppressant drugs are helpful in relieving nausea and vomiting in the acute phase of the disease; however, they are of no therapeutic value for the protracted disequilibrium following involvement of the second ear. An awareness of this disorder as a disease entity will minimize diagnostic and therapeutic frustration on the part of the physician and provide a realistic prognosis for the patient. Unfortunately, the prognosis is for permanent but somewhat lessening disequilibrium with the passage of time and depends in great part on the subject's age. PMID- 4037227 TI - Behavioral conditioning and experimental motion-induced sickness. AB - Adult male squirrel monkeys were the subjects of experiments conducted to determine whether or not repeated exposures to sickness-inducing horizontal rotation would result in behavioral conditioning of emetic responses. The development of conditioned food aversion and feeding suppression as a consequence of pre- and postrotation eating was quantified. It was concluded that neither instrumental conditioning nor classical conditioning were valid alternative hypotheses for the occurrence of repeated vomiting episodes over a period of ten daily exposures to motion. Conditioned aversion to fresh banana and feeding suppression developed gradually if rotation, which induced multiple bouts of vomiting, was sustained for 1- or 2-hour sessions. If spinning was terminated immediately after the first emetic response, no aversion or suppression emerged. The occurrence of food aversion, by itself, is questioned as a valid index of the presence of subjective concomitants of motion sickness in animals. PMID- 4037228 TI - Quantitative effects of nasal surgery on olfaction. AB - A prospective study of 100 patients undergoing nasal surgery was done to quantitate the effects of nasal surgery on olfaction. Patients were evaluated pre and postoperatively with regard to their subjective olfaction, and pre- and postoperative olfactograms were obtained using a simple office olfactometer. Thirty-two patients had normal olfaction during the course of study. Forty-nine improved following surgery. Eight patients had a decrease in olfaction after surgery. Two of these were related to allergic rhinitis. One patient had a total loss of olfaction following a septorhinoplasty. The authors conclude that most patients undergoing nasal surgery will have either an improvement or no change in olfaction after surgery. PMID- 4037230 TI - Antibody activity of IgG subclasses against pneumococcal polysaccharides after vaccination. AB - The isotypic pattern of antipneumococcal polysaccharide antibodies with respect to IgG subclasses differs in adults and children. Adults show almost exclusively IgG2 activity, whereas children exhibit both IgG1 and IgG2 activity. The IgG subclass pattern of the antibody response after pneumococcal vaccination was evaluated in nine healthy children 1 to 2 years of age, eight healthy children 5 to 6 years old, and eight healthy adults. The number of individuals responding increased with age, and the response was mainly of the IgG1 subclass. The implications of this finding are discussed. PMID- 4037229 TI - Transepithelial cation movements in gerbil utricles. AB - The inner ear epithelium secretes potassium (K+) and absorbs sodium (Na+). The authors' experiments utilized, for the first time, isolation of the nonsensory from the sensory regions of the utricle in the vestibular labyrinth of the gerbil by means of injecting insulating seals. It was found that the isolated nonsensory region accumulated rubidium (Rb+) (as a marker for K+) in the endolymph to a level of eight times (41 mmol/l) that in the incubation medium (5 mmol/l) over a 90-minute period. However, Na+ rose during this period, suggesting that cells excluded from this preparation (sensory regions) may be involved in Na+ reabsorption. Further observations of the time course of changes in the luminal concentrations of cations suggested that the endpoints observed at 90 minutes represented a new steady state in which both Na+ and K+ concentrations were higher and lower, respectively, than under control conditions (by about 40 mmol/l each), but they were still each displaced from electrochemical equilibrium. This implies that the processes of Na+ absorption and/or K+ secretion may be shared in some way between the two regions. This finding is unexpected, based on previous models of endolymph production, in which ionic regulation has been assigned to nonsensory regions alone. PMID- 4037231 TI - Effect of atropine and carbachol on vestibular compensation in squirrel monkeys. AB - The central cholinergic system's involvement in vestibular compensation has been clearly demonstrated in the infra-human primate model. In the squirrel monkey, long after unilateral labyrinthectomy, atropine injection produced significant reduction of slow-phase eye velocity of the spontaneous nystagmus. The atropine effect was also depicted through the dynamic vestibular inputs, reducing the maximum slow-phase eye velocity of damped pendular rotation nystagmus. Contrary results (increased slow-phase eye velocities) were found after carbachol injection. After atropine injection, the locomotor deviation count increased significantly, more to the nonlesion side. Carbachol injection engendered the opposite result. After bilateral labyrinthectomy, no significant effect was found from drug injection. Thus, our findings suggest that atropine's major site of action after unilateral labyrinthectomy is the vestibular nuclei on the intact side. PMID- 4037232 TI - [The degree of endothelial desquamation in normal pregnancy and the puerperium]. PMID- 4037233 TI - [Quantitative drug exchange in the maternal-placental-fetal system. Studies of transplacental lidol transport]. PMID- 4037234 TI - [High annular constriction dystocia of the uterus during labor]. PMID- 4037235 TI - [Tying off the umbilical cord with a rubber ring]. PMID- 4037236 TI - [Comparative study of 2 new methods of anesthesia induction in cesarean section- their effect on maternal, fetal and neonatal parameters]. PMID- 4037237 TI - [Comparative study of epidural and general anesthesia in planned cesarean section]. PMID- 4037238 TI - [Anesthesia during labor via epidural analgesia. II. Its effect on the fetus and newborn infant]. PMID- 4037239 TI - [Orchiectomy in spermatic cord torsion--hormonal and spermatological research]. PMID- 4037240 TI - [Epithelial tumors of the ovary with a low malignant potential. I. Histogenesis, morphology and diagnosis]. PMID- 4037241 TI - [Does vaginal adenosis exist in Bulgaria?]. PMID- 4037242 TI - Antithrombin III concentrates for treatment of disseminated intravascular coagulation in children. AB - Six children (1 month to 5 years old) with DIC were treated with bolus injection of AT-III concentrates and/or continuous heparin infusion. In one case, when AT III concentrates were administered without heparin, the platelet count was normalized in accordance with a rise in the plasma AT-III level. In the other children, who were treated with both AT-III concentrates and heparin, most of the abnormalities in coagulation studies were normalized within 5 days in four of five cases. These findings suggest that the administration of AT-III concentrates may significantly enhance the therapeutic efficacy of heparin, and that the use of AT-III concentrates with heparin is a safe and effective regimen for the treatment of childhood DIC. PMID- 4037243 TI - Chronic transfusions in patients with sickle cell disease. Indications and problems. AB - The use of chronic transfusions in patients with sickle cell disease is now the common practice after a stroke has occurred, in order to prevent the highly probable recurrence. Clinical studies show that chronic transfusion prevents the recurrence of a stroke. Review of the natural history of sickle cell disease indicates, however, that the mortality and morbidity associated with hemoglobin SS disease are quite high. Use of chronic transfusion, given before the occurrence of stroke and other irreversible organ damage, can be considered as an alternative to the conservative management of sickle cell disease. Chronic transfusion has become practicable since the recent advances in chelation therapy have essentially eliminated the risk of secondary iron overload. PMID- 4037244 TI - Ethical issues in cooperative cancer therapy trials from a statistical viewpoint. I. A general overview. AB - In conducting collaborative cancer therapy trials, investigators have an obligation to answer relevant and realistic research questions, while providing the patient with quality treatment. They should participate only in well conceived, well-designed protocols. Their patients should follow the protocol as closely as possible. Protocol violations are admissible only in extreme cases, instances in which the patient's well-being is clearly best served by this violation. The participating clinicians have the obligation to submit quality and timely data. Finally, the results of each study must be written up in such a fashion that the reader has a clear understanding of the goals and outcomes of the trial. PMID- 4037245 TI - Ethical issues in cooperative cancer therapy trials from a statistical viewpoint. II. Specific issues. AB - Quality collaborative clinical trials cannot be run without the complete commitment of every investigator. The clinician must provide quality data and must submit the data on time. The statistical office and protocol coordinator are responsible for maintaining confidentiality and for keeping a watchful eye on the overall conduct of the study. Safety monitoring of experimental drugs or drug combinations is a central responsibility, since individual investigators generally only see the statistical reports on the study, rather than the raw data. It is critical that interim statistical reports be interpreted correctly so as not to affect accrual adversely. A separate issue discussed in this article is the answering of negative questions. Can therapy be reduced and still obtain equal efficacy? Such studies are based on sound ethical considerations, but they are hazardous since they could lead to serious worsening in cure rates. PMID- 4037246 TI - Transient myeloproliferative syndrome in a phenotypically normal infant. PMID- 4037247 TI - Transient granulocyte maturation arrest: discovery by flow cytometry of a variant form of agranulocytosis. AB - A 5-year-old child presented with pneumonia and agranulocytosis. A Wright-stained peripheral blood smear showed only cells which had the morphological appearance of lymphocytes, plus a few monocytes and eosinophils. A bone marrow aspirate smear showed a complete lack of recognizable granulocyte precursors. However, the admission CBC and differential performed by automated flow cytochemistry (Technicon Instruments Corporation H-6000) measured 32% granulocytes as determined by peroxidase activity. Cytochemical stains on the blood and marrow smears revealed that many of the cells that had the morphological appearance of lymphocytes were positive for myeloperoxidase activity. Special studies on these cells revealed them to be abnormal, intermediate granulocytes with azurophilic, peroxidase-containing primary granules, but with few secondary granules and limited lactoferrin activity. Over 28 days the child recovered, first with granulocytic hyperplasia in the marrow and then a return of the peripheral blood to normal. This is the first case report of an episode of transient "agranulocytosis" which in reality was a maturation arrest. PMID- 4037248 TI - Hematologic changes during acute chest syndrome in sickle cell disease. PMID- 4037249 TI - [Chronic urticaria: etiology and diagnosis]. PMID- 4037250 TI - [Bronchodilator effect of fenoterol in acute asthma and after 2 weeks]. PMID- 4037251 TI - [Bronchial asthma and ketotifen. Open clinical study of children]. PMID- 4037252 TI - Effects of Ca2+ antagonist, nicardipine, on experimental asthma with special reference to slow reacting substance of anaphylaxis. AB - Slow reacting substance of anaphylaxis (SRS-A) is an important chemical mediator of bronchial asthma. Leukotriene C4 is a component of SRS-A and is synthesized from arachidonic acid. Its synthesizing and releasing processes are found to be Ca2+-dependent. We developed an in vivo inhalation asthma model, mainly mediated by SRS-A, and elucidated the relationship between a Ca2+-antagonist, nicardipine, and SRS-A. In the asthmatic model, mediated by endogenous SRS-A induced by antigen inhalation, continuous intravenous infusion of nicardipine 7 micrograms/kg/min depressed the open airway pressure by about 60% compared with the saline-treated group. Inhibition of mean pulmonary resistance (RL) was about 50% and that of the inverted value of dynamic compliance (1/Cdyn) about 36%. However, the same concentration of nicardipine did not significantly effect the airway response in the asthmatic model induced by the inhalation of leukotriene C4. These results suggest that nicardipine, at the concentration used in the present study. did not block the direct effect of SRS-A on the smooth muscle, but blocked the Ca2+ influx required for the synthesis of SRS-A and its release. PMID- 4037253 TI - A study of serum antibody activity in workers with occupational exposure to diphenylmethane diisocyanate. AB - The prevalence of sensitization was studied in a group of 76 foundry workers with occupational exposure to diphenylmethane diisocyanate (MDI). Ten workers had clinical evidence of asthma, 40 had non-asthmatic respiratory symptoms, and 26 were asymptomatic. Specific IgE antibodies to MDI were found in two workers (2.6%) and specific IgG antibodies, in five workers (6.6%). The prevalence of IgE and IgG antibodies was higher in the 10 subjects with asthma than in the non asthmatic group. The prevalence of anti-paratolyl-monoisocyanate antibodies was not significantly different from that of anti-MDI antibodies, and both haptenic determinants displayed a high degree of cross-reactivity in the RAST inhibition test. The role of humoral immunological mechanisms in MDI-induced asthma is unclear in view of the rather low prevalence of these serum antibodies in this group of workers. PMID- 4037254 TI - Diagnostic tests in allergy to green coffee. AB - Twenty-two coffee roastery workers with work-related symptoms of various degree from the eyes, nose or bronchi were tested with partly purified water-soluble extract from dust of green coffee beans (GCB). Eighteen persons had a positive prick test, eight a positive bronchial provocation test and seven a positive nasal provocation test. Fourteen had a positive methacholine test, indicating unspecific bronchial hyperreactivity. Specific IgE antibodies to GCB extract were found in sera of 11 workers and to castor bean (CB) extract in 16. The workers measured their lung function with an air flow meter, three times a day for 1 week, and the values were lower in the second half of the week for the workers with IgE antibodies to GCB, but not for the others. It is concluded that the case history, prick test, RAST, and simple lung function tests for one or a few weeks are the best tools when investigating occupational allergy. When the allergen is unknown, but the occurrence of an IgE-mediated allergy is suspected, serial lung function measurements and determinations of total serum IgE, in addition to taking a careful case history, are valuable methods with which to start the investigation. PMID- 4037255 TI - Reproducibility of histamine skin prick test. Inter- and intravariation using histamine dihydrochloride 1, 5, and 10 mg/ml. AB - The reproducibility of skin prick test using histamine dihydrochloride 1, 5, and 10 mg/ml was tested by three nurses in five non-atopics in a double-blind trial. The variations day-to-day, within-day, between and for the same tester were calculated. Seventy-five percent of wheal reactions obtained by histamine 1 mg/ml were less than 15 mm2. With histamine 5 mg/ml there were only a few wheals less than 15 mm2 and none at all with histamine 10 mg/ml. The mean coefficient of variation of wheals greater than 15 mm2 was between 20-30%, in contrast to figures between 30-60% with wheals less than 15 mm2. No significant day-to-day or within-day variation was shown concerning histamine wheal areas. It is suggested that histamine dihydrochloride 10 mg/ml should replace histamine dihydrochloride 1 mg/ml as the positive reference in routine skin prick tests and biological standardization. PMID- 4037256 TI - Nasal challenge with serotonin and histamine in normal persons. AB - In order to study the nasal response to serotonin, 14 normal persons, in a double blind study, were provoked in the nose with serotonin and histamine. Itching and the number of sneezes were noted, the amount of secretion measured, and nasal airway resistance recorded by active posterior rhinomanometry. Serotonin induced significant nasal itching, sneezing and hypersecretion, similar to the effects of histamine. The effect of serotonin on nasal airway resistance, on the other hand, was slight (+ 10%) and insignificant in contrast to that of histamine in equipotent doses (+ 48%) (P less than 0.001). In conclusion, we have shown that serotonin provocation can induce a rhinitis response in the human nose. The nasal symptoms suggest an effect on sensory nerves with reflex-induced sneezing and hypersecretion, while there appears to be little direct effect on capacitance vessels. The possible role of serotonin as a mediator of rhinitis remains speculative. PMID- 4037257 TI - Persistent subcutaneous nodules in children hyposensitized with aluminium containing allergen extracts. AB - A follow-up study of 202 children who had received hyposensitization with aluminium-containing allergens showed that 1-3 years after cessation of hyposensitization 13 children still had severely pruiginous treatment-resistant subcutaneous nodules in their forearms. Because of their long persistence the nodules of six children were studied in detail. Histologically, the nodules showed infiltration with lymphocytes (forming germinal centres), macrophages, plasma cells, mast cells and a few eosinophils. In five patients aluminium crystals were found scattered between the cells and, in addition, the phagosomes of the macrophages contained aluminium. Patch tests for aluminium were positive in four of the six patients. It is concluded that persisting nodules during hyposensitization with aluminium-containing allergens may indicate development of aluminium hypersensitivity, and if this is confirmed hyposensitization should be discontinued. PMID- 4037258 TI - Clustered immunotherapy with Yellow Jacket venom. Evaluation of the influence of time interval on in vivo and in vitro parameters. AB - To evaluate difference in clinical efficacy, side effects, in vivo and in vitro parameters, 25 patients allergic to Yellow Jacket were treated with clustered immunotherapy using either 7 or 14 days interval between clusters. Twenty-one patients completed the 6 months' treatment period and four were withdrawn due to adverse reactions (2 cases of anaphylactic shock). Sixteen patients were challenged by in-hospital sting and the clinical efficacy was complete. Local side effects were observed in the majority of patients, but only rarely limited the course of immunotherapy. Skin sensitivity estimated as the venom concentration eliciting a wheal equal to histamine HCl 0.1 mg/ml using intradermal test was significantly reduced after 6 months of treatment. Specific IgE showed an initial increase, thereafter declining to pretreatment levels. IgG subclasses were determined by a triple antibody assay. Only subclasses 1 and 4 showed response. Subclass 4 showed a steady increase contrary to subclass 1 which decreased after reaching maintenance dose. No unambiguous relation between either the absolute value or the change of IgG1 and IgG4 at the time of challenge was observed in the patients who tolerated a sting. Furthermore, the IgG response was not correlated to the cumulative dose of venom administered. No simple regulatory function of IgG subclasses in the skin and IgE response was found, and the occurrence of local side effects did not seem to be determined by IgG antibodies. We conclude that clustered immunotherapy with Yellow Jacket venom is highly effective and that the frequency of side effects is acceptable.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4037259 TI - [Acid-base equilibrium in anesthesiology and operative intensive care medicine. Physiology, pathophysiology and clinical aspects of alkalosis and mixed disorders]. AB - This review details basic and clinical aspects of metabolic and respiratory alkalosis and mixed acid-base disturbances. New experimental results show that NH4Cl and arginine-HCl should no longer be used in antialkalotic therapy because they increase intracellular pH and have no effect on intracellular bicarbonate concentration. Appropriate HCl solutions should be employed in severe metabolic alkalosis because they reduce pH and the bicarbonate concentrations in both body compartments. PMID- 4037260 TI - [Anesthesia in craniofacial interventions in childhood]. AB - Nine children with severe craniofacial malformations underwent eleven major reconstructive craniofacial osteotomies; in two children, cranio-orbito-facial reconstructions were performed. Anaesthesia lasted from seven to eleven hours. The anaesthetic technique consisted of inhalation anaesthetics and supplementation with narcotics. Intraoperative problems were seen mainly regarding the protection of airways, the body temperature, and the extensive blood loss. At the end of anaesthesia all children were awake, three were extubated in the operating room. In children with mid-face advancement the nasotracheal tube was left in place for at least 48 hours. PMID- 4037261 TI - [Comparative studies on dose adjustment of intraoperative lidocaine therapy in heart failure patients]. AB - From 10 patients with myocardial insufficiency arterial blood samples were taken, in order to study lidocaine plasma concentrations following reduced iv. bolus administration (0.5 mg/kg body weight) and subsequent infusion (2 mg/min). Drug concentrations were monitored by means of gas chromatography. The results obtained from the reduced loading dose of lidocaine were nearly identical to those from patients without myocardial insufficiency and an iv. bolus injection of 1 mg lidocaine/kg body weight. The reduced hepatic metabolism of lidocaine caused by manifest myocardial insufficiency requires a significantly reduced loading dose not exceeding the therapeutic range, even in intraoperative short term use. PMID- 4037262 TI - [Relaxograph--an improved technic for measuring relaxation]. AB - The Relaxograph offers a facile measurement technique for relaxation. Electromyographic registration allows this technique to be used even in extreme positioning of the patient. Placement of the electrodes, calibration and measurement can be learned and applied in a very short time. Simple operation enables immediate and undisturbed working with this measurement system which is ideally suited for clinical routine. The problems encountered with the predecessors of this series in respect of calibration and measurement on the previously relaxed patient, have been largely done away with by this new concept. PMID- 4037263 TI - [Our experience with biocompatible ossicle prostheses]. PMID- 4037264 TI - [Brainstem potentials in the diagnosis of multiple sclerosis]. PMID- 4037266 TI - Science and anaesthesia. PMID- 4037265 TI - [External malignant otitis]. PMID- 4037267 TI - Epidural diamorphine and the metabolic response to upper abdominal surgery. AB - The effect of the administration of diamorphine 10 mg epidurally on the metabolic response to cholecystectomy was investigated and compared with a control group of patients given intravenous papaveretum. There were no significant differences in blood glucose, lactate and pyruvate, and plasma nonesterified fatty acid values between the epidural diamorphine group and the control group. Plasma cortisol concentrations were significantly lower in the epidural diamorphine group postoperatively and this was associated with a marked improvement in pain relief. We conclude that epidural opiates do not directly influence the metabolic response to surgery, but decrease the cortisol response postoperatively secondary to improved analgesia. PMID- 4037268 TI - Epidural meptazinol for pain relief after lower abdominal surgery. AB - A preliminary investigation is reported into the use of epidural meptazinol for pain relief in 20 patients after major lower abdominal (gynaecological) surgery. Analgesia was rapid in onset (15 minutes), had a median duration of 124 minutes (interquartile range 85-212 minutes) after a single dose of 30 mg and a median duration of 122.5 minutes (interquartile range 70-127 minutes) after a single dose of 60 mg. Overall pain relief, as judged by the patients themselves, was satisfactory in 19 out of the 20 cases. At 30 minutes and 45 minutes pain relief was significantly better with the 60 mg than the 30 mg dose (p less than 0.02). No drug-related adverse effects were observed during the study. PMID- 4037269 TI - Failed intubation. Six years' experience in a teaching maternity unit. AB - Between 1978 and 1983, the tracheas of eight patients could not be intubated in the maternity unit of St James' University Hospital, Leeds. The incidence of failed intubation on our labour ward is approximately one for every 300 general anaesthetics given. The results of postoperative investigation in the patients are reported. PMID- 4037270 TI - Extracranial surgery--intracerebral tumour. AB - A case is described in which localising neurological signs developed on the first day following general anaesthesia for insertion of a silastic implant over a frontal fracture. Despite prompt appropriate investigation seven weeks elapsed before the correct diagnosis was made. Aspects of the management of patients who develop a neurological deficit soon after general anaesthesia are discussed. PMID- 4037271 TI - Anaesthesia in dysautonomia: further complications. AB - A case is described of a patient, known to be suffering from idiopathic autonomic neuropathy, who underwent general anaesthesia for repair of a fractured neck of femur. In addition to profound hypotension, unexpected respiratory depression occurred which has not previously been described in this condition. Other unusual features of this patient's condition are also discussed. PMID- 4037272 TI - Severe hypertension during anaesthesia for dacryocystorhinostomy. AB - A healthy 82-year-old woman presented for dacryocystorhinostomy under general anaesthesia. Following the application of intranasal cocaine and subcutaneous injection of felypressin she developed severe hypertension, multiple ventricular ectopic beats and depression of the ST segment on the electrocardiogram. A drug interaction is suspected. PMID- 4037273 TI - The Penlon Bromsgrove high frequency jet ventilator for adult and paediatric use. A solution to the problem of humidification. AB - The Penlon Bromsgrove is a new high frequency jet ventilator, suitable for use in both adults and children. The jet stream is humidified by means of an integral in line Bernoulli nebuliser. The self-recharging nebuliser can also convey drugs directly to the airways in the form of an aerosol. Alarms and fail-safe systems are incorporated. A pressure gauge continuously displays the jet drive pressure. There are two digital LED displays; one shows jet frequency in breaths per minute; the other, the jet drive pressure, minimum, maximum and mean patient airway pressures. Two fail-safe systems ensure that these pressures do not become excessive. Both audible and visual alarms are provided. The prototype has proved to be quiet and completely reliable over more than 4000 hours use, with no bronchoscopic or histological evidence of ineffective humidification. PMID- 4037274 TI - Adverse anaesthetic reactions. An update from a proposed national reporting and advisory service. PMID- 4037275 TI - 'Allergic' drug reactions during anaesthesia. PMID- 4037276 TI - Pseudohypertension. PMID- 4037277 TI - Diazepam premedication in children. PMID- 4037278 TI - Assessment of the Dinamap 845. PMID- 4037279 TI - Naloxone in cardiorespiratory arrest. PMID- 4037280 TI - Oxygen therapy and minitracheostomy. PMID- 4037281 TI - Anaesthesia for the correction of scoliosis. PMID- 4037282 TI - Intra-articular bupivacaine for pain relief in arthroscopic surgery. PMID- 4037283 TI - Tissue expanders complicating intubation. PMID- 4037284 TI - [Comparative study of analgesia and plasma level following rectal, intramuscular and intravenous administration of ketamine]. AB - Ketamine 25 mg/kg was administered to five foxhounds by the intravenous, intramuscular or rectal route. Plasma concentrations were measured by gas chromatography and analgesia was tested by two techniques. Intravenous application gave reliable analgesia and well reproducible plasma levels in all subjects. Distribution and elimination half lives were found to be 6 min and 55 min, respectively. Intramuscular injection resulted in peak-plasma levels around the twentieth minute, elimination half life was fifty-two minutes, bioavailability 90%. Analgesia proved satisfactory in four out of the five subjects and lasted longer than after intravenous injection. The rectal route produced a wide range of peak-plasma levels, the average peak appearing after 40 min. We found an elimination halflife of 43 min and a bioavailability of 30%. Analgesia was poor in four out of the five subjects. The low plasma levels following rectal application are due to the poor bioavailability and this appears to be the reason for the unsatisfactory results with this route of administration. Bioavailability depends on the site of application (drainage mainly through the vena cava or portal vein) and the pH of the rectum. PMID- 4037285 TI - [The effect of rewarming of stored blood on plasma value and erythrocytes]. AB - 30 units of stored blood of different age were rewarmed from 4 degrees C to 32 degrees C by microwave blood-warmer Infusotherm 407. The resulting damage to blood components and change of function of erythrocytes were compared with those caused by storage of CPD-blood. Dependent on the age of stored blood we found considerable increases in the plasma-levels of potassium, lactate, and free haemoglobin. Compared with cold CPD-blood rewarming of stored blood produced a 7% increase in lactate and a 8% increase in free haemoglobin. There were no changes in platelet and erythrocyte counts, haematocrit, plasma-levels of haemoglobin, electrolytes, cholesterol, blood viscosity, osmotic resistance, and oxygen binding capacity. As damage of stored blood produced by warming is minimal compared with that produced by storage, the Infusotherm 407 is considered to be a clinically useful blood-warmer. PMID- 4037286 TI - [How safe is the rectal induction of narcosis with methohexital in pediatric anesthesia?]. AB - A 6 year old boy developed a rebound of anaesthesia with abolition of reflexes and spontaneous respiration 100 min after anorectal induction with methohexitone and 20 min after extubation. The role of reliable observation during postoperative period in this type of anaesthesia is emphasized. PMID- 4037287 TI - [Remarks on the work of F. Incze et al. Modified methods for carrying out non intubation anesthesia for laryngomicroscopic interventions]. PMID- 4037288 TI - [Experiences with Swan-Ganz-catheter placement in the external jugular vein]. AB - Clinical experience concerning the placement of Swan-Ganz catheters (SGC) via the external jugular vein is presented. After puncture of either the right or left external jugular vein, placement of SGC was possible in 90 per cent of patients. Compared to techniques involving puncture of the internal jugular vein this method has less complications. The placement of 167 SGC could be done without any problems, thus proving that the external jugular vein is a safe way of insertion. The external jugular vein as a primary route can be recommended if the vein is visible, especially in cases where puncture of the internal jugular vein may be difficult and could only be performed with an increased risk of complications. PMID- 4037289 TI - [A simple method for monitoring spontaneous respiration]. AB - For respiratory monitoring of spontaneously breathing patients in the operation theatre, recovery room and intensive care ward a gauze attached on the nose may be used successfully. This continuous optical and practically cost-free aid has proved to be valuable in such cases when electronic monitoring is not available. PMID- 4037290 TI - [Endotest--a simple method for the monitoring of internal pressure of the tube cuff]. AB - The Endotest is a simple device for monitoring the cuff pressure of an endotracheal tube. No complications could be observed during a 6 month period of usage in the daily routine. We found the handling very good and cuff pressure monitoring very useful. PMID- 4037291 TI - Application of the dual-cell coulometric detector: a method for assaying monoamines and their metabolites. AB - A new HPLC assay technique for monoamines and their metabolites, using a controlled potential coulometric detector equipped with a dual working electrode cell of fully porous graphite through which the samples flow, is described in comparison with a classical amperometric detector equipped with a glassy carbon electrode. Different potentials can be applied at each cell of the coulometric detector to improve sample resolution and detection sensitivity. The signal-to noise ratio (s/n) calculated in similar conditions was 10 times lower for the coulometric detector than for the amperometric one. The dual-coulometric detector does not undergo daily decay or variation, and needs no particular care or preparation. It is therefore possible to achieve stable routine sensitivity in a range of 10 fmol. This new technique has been applied for assaying monoamines and their precursors and metabolites by direct injection of clear supernatant after centrifugation and for determination of catecholamine turnover in rat pineal gland and neuro- and adenohypophysis in samples purified by Al2O3 adsorption. PMID- 4037292 TI - Subcellular fractionation of wheat leaf protoplasts by centrifugal elutriation. AB - A new method using centrifugal elutriation for subcellular fractionation of plant cells has been developed. This method takes advantage of the fact that particles sedimenting in a gravitational field can be eluted by flow against the field. A wheat protoplast homogenate was fed into an elutriation rotor spinning at high speed and the flow rate into the rotor was gradually increased. The smaller and less dense materials such as mitochondria, microbodies, endoplasmic reticulum, and cytoplasm were elutriated earlier than the larger and denser nuclei and chloroplasts. The intact chloroplasts, free of mitochondria, microbodies, endoplasmic reticulum, and cytoplasm, could be obtained within 40 min following the rupture of protoplasts. The chlorophyll-free mitochondria could be obtained within 80 min. PMID- 4037293 TI - The recovery of nitrocellulose-bound protein. AB - Conditions for the electroelution of protein from polyacrylamide gels to nitrocellulose and its subsequent recovery have been examined. A procedure is described whereby soluble material suitable for further analysis can be obtained. Nitrocellulose-bound protein is dissolved in acetone. It can be precipitated from solution in the presence of a carrier such as Polybrene in a form that can subsequently be solubilized in good yield. PMID- 4037294 TI - The identification of neotrypsinogens in samples of bovine trypsinogen. AB - Isoelectric focusing of commercial samples of bovine trypsinogen detected a component with a lower isoelectric pH than that of trypsinogen. The isoelectric pH was 8.75 compared to 9.3 for trypsinogen, and the amount of the component varied from 16 to 41% of the total protein. The protein (24,000 Da) was converted to fragments of 13,800 and 10,500 Da on reduction with dithioerythritol, showing that the component was a modified form of trypsinogen containing a cleaved peptide bond. The cleavage site was established from the study of four polypeptide fragments which were isolated from the fully reduced and S carboxymethylated trypsinogen. The molecular weights, amino acid compositions, and amino-terminal sequences of these fragments identified a cleavage of Lys 131 Ser 132, namely from a Ser-neotrypsinogen, or at Arg 105-Val 106, from a Val neotrypsinogen. Val-neotrypsinogen was the more abundant of the two and was approximately 71% of the total neotrypsinogen in the trypsinogen sample. Both neotrypsinogens were converted to active trypsin molecules in high yields, showing that the zymogens closely resembled the conformation of intact trypsinogen. Presumably, the neotrypsinogens were produced during the isolation of the zymogen when pancreatic tissue was partly autolyzed and active trypsin was present. PMID- 4037295 TI - Matrix modifiers in graphite furnace atomic absorption analysis of trace lithium in biological fluids. AB - The use of KH2PO4/NH4NO3 as matrix modifier eliminates severe interference effects on the atomic absorption analysis of lithium in biological fluids. This enables determination of trace lithium in microliter size samples with absolute sensitivity (0.0044 absorbance) of 2 pg. There is no requirement for standard additions experiments to correct for interferences in specific matrices such as serum and saliva. The biological half-life of trace lithium was 16.9 +/- 2.8 h. Saliva lithium is a good estimate of serum level; the two are highly correlated (r = 0.97) and saliva level is about three times serum. PMID- 4037297 TI - Flow-through pH-stat method for lipase activity. AB - A new method for lipase activity which combines the simplicity and rapidity of continuous pH-stat methods with the flexibility in choice of conditions (pH, temperature, etc.) of manual methods is described. The lipase-catalyzed hydrolysis of olive oil and titration of fatty acid products can be carried out separately in two small continuously stirred reactors in series. The response is linear with enzyme dilution. PMID- 4037296 TI - Computer analysis of double-labeled two-dimensional electrophoresis gels. AB - A computerized process for the automatic analysis of double-label autoradiography after two-dimensional polyacrylamide gel electrophoresis has been developed. Matching fluorographs and autoradiographs produced from gels containing 3H- and 14C-labeled proteins are digitized by a rotating drum densitometer and analyzed by the Man-computer Interactive Data Analysis System III. This system locates corresponding protein spots in the films with edge-detection algorithms, converts spot density readings to isotopic disintegrations by reference to standard curves, and computes a 3H:14C ratio for each spot in the gels. On the average, calculated ratios are accurate to approximately 9% for test strips of polyacrylamide gel containing uniform mixtures of 3H and 14C. Values obtained for two-dimensional gels containing n protein spots with a known 3H:14C ratio of 8.6 +/- 0.1 are as follows: 8.1 +/- 1.4 (n = 268), 8.8 +/- 2.1 (n = 278), 9.1 +/- 1.7 (n = 245), and 8.8 +/- 2.2 (n = 223). The computer process greatly reduces the time required to precisely compare two complex protein mixtures and has sufficient precision to detect a doubling in the biosynthesis of any individual protein. PMID- 4037298 TI - Quantitative identification of N-terminal amino acids in proteins by radiolabeled reductive methylation and amino acid analysis: application to human erythrocyte acetylcholinesterase. AB - A novel method of determining N-terminal amino acids in proteins is introduced. Reductive methylation of a protein with radiolabeled formaldehyde methylates both the alpha-amino group of the N-terminal amino acid and the epsilon-amino groups of Lys residues. The radiomethylated amino acids are stable to acid hydrolysis, and each of 16 possible hydrolysis-stable N-terminal amino acids can be identified by the unique elution positions of its N alpha-methyl and N alpha,N alpha-dimethyl derivatives with an appropriate amino acid analyzer elution schedule. The technique is at least as sensitive as other N-terminal amino acid determinations and, in addition, permits a quantitative evaluation of the number of N-terminal groups in a sample. Reductive methylation of bovine serum albumin revealed N-terminal Asp at a stoichiometry of 0.97 amino acid residue per polypeptide, while methylation of prolactin resulted in 0.86 residue of N terminal Thr per polypeptide. Human erythrocyte acetylcholinesterase contained two N-terminal amino acids with stoichiometries of 0.66 Glu and 0.34 Arg per 70 kDa subunit. Identification of Glu as the principal N-terminus of acetylcholinesterase was confirmed by Edman sequencing. PMID- 4037299 TI - Procedure for isolation of gangliosides in high yield and purity: simultaneous isolation of neutral glycosphingolipids. AB - While several methods for ganglioside extraction and isolation have been described, relatively little attention has been given to the effectiveness of separation from peptides, phospholipids, and various low-molecular-weight contaminants. A procedure is described for isolation of gangliosides in high purity and good yield from 1- to 400-mg samples (wet wt). A key step was mild acidification following homogenization, designed to dissociate gangliosides from lipophilic peptides which coextracted into organic solvents. This has proved particularly helpful for myelin and myelin-containing tissues (e.g., white matter, nerve) whose proteins have presented special problems in ganglioside isolation. In this study isolation was effected by consecutive chromatographies on Sephadex LH-20, DEAE-Sephadex, and silica gel following the initial acidification. The method applied to bovine white matter gave tissue concentrations (calculated from yields and radiolabeled tracer recoveries) that were similar to those obtained with three previously described procedures; however, peptide contaminants were an order of magnitude lower. Removal of low molecular-weight contaminants, including nucleotide sugars, was virtually complete. In addition to ganglioside isolation the method can be used to obtain neutral glycosphingolipids as well. It is believed to have broad applicability to a diversity of tissues. PMID- 4037300 TI - Enzymatic lactate-specific radioactivity determination in biological samples. AB - A method for the measurement of specific lactate radioactivity in biological samples is presented. It is based on the following steps: (a) enzymatic conversion of lactate to pyruvate, (b) pyruvate conversion to 2,4 dinitrophenylhydrazone, (c) concentration-separation of the latter in reusable Amberlite XAD-7 polymeric adsorbent columns, and finally (d) estimation of the radioactivity thus retained compared with that of enzymatically untreated aliquots of the same samples. Specificity was ensured by the use of lactate dehydrogenase as specific recognizing agent for lactic acid. No interference from glucose, lactate, or amino acids was observed. The method presented is simple and can be applied in routine multiple estimations of lactic acid radioactivity in conjunction with the enzymatic measurement of lactate in biological samples in tracer metabolic studies. PMID- 4037301 TI - Colorimetric micromethod for the determination of protein in solutions with silver ions and dithizone. AB - A method of determination of protein based on the measurement of complexed Ag+ and AgCl absorbed on the macromolecules is described. This reaction is carried out in the presence of chloride ions and detergents (Triton X-100 or SDS) in alkaline solution. The silver ions are detected with dithizone. With this method it is possible to estimate 0.1 microgram bovine serum albumin in 0.5 ml sample with a coefficient of variation of 16%, and 1.5 micrograms/sample with a coefficient of variation of 3.6%. The method is simple, rapid, inexpensive, and very sensitive. PMID- 4037302 TI - Preparative isolation of peroxisomes from liver and kidney using metrizamide density gradient centrifugation in a vertical rotor. AB - A method for the preparative isolation of peroxisomes from the livers of rat, guinea pig, and mouse, and also from rat kidney is described. The light mitochondrial fraction, i.e., particles sedimenting between 33,000 and 250,000g min, or the postnuclear supernatant of liver or kidney, is subjected to a 20-50% Metrizamide density gradient ultracentrifugation in a vertical rotor. After centrifugation, the peroxisomes (marker enzyme catalase and dihydroxyacetone phosphate acyltransferase) sedimented as a band near the bottom of the tube (rho = 1.22 g/ml). From the distribution of different marker enzymes and also from the morphometric examinations, it was demonstrated that the isolated peroxisomes are not contaminated with lysosomes, mitochondria, or microsomes. PMID- 4037303 TI - A method for isolation of cytoplasmic RNA from a slime mold, Physarum polycephalum. AB - A procedure for fast and simple preparation of cytoplasmic ribonucleic acid from Physarum polycephalum microplasmodia is described. Microplasmodia are homogenized in a high-magnesium-high-ethylene glycol bis(beta-aminoethyl ether) N,N' tetraacetic acid buffer and nuclei are pelleted. The supernatant is extracted with sodium dodecyl sulfate-phenol-chloroform and crude RNA is precipitated. This is further purified by selective ethanol precipitation from 6 M guanidinum hydrochloride. This RNA preparation is suitable for direct use in hybridization studies. PMID- 4037305 TI - Generating sucrose gradients in three minutes by tilted tube rotation. AB - A technique which permits rapid preparation of sucrose gradients with highly reproducible profiles is described. Tubes are filled with equal volumes of light and heavy sucrose solutions, sealed, and rotated for 3 min tilted 80 degrees from vertical. Linear 5-20% and 5-30% gradients and nonlinear but useful 5-45% gradients are obtained. PMID- 4037304 TI - Copper chelates as probes of biological systems: stable copper complexes with a macrocyclic bifunctional chelating agent. AB - Monoclonal antibodies tagged with chelated metal ions have numerous potential applications. Here we report the synthesis of a new "bifunctional" metal chelator, 6(p-bromoacetamidobenzyl)-1,4,8,11-tetraazacyclotetradecane- N,N',N",N"' -tetraacetic acid, which can be covalently attached to proteins and which binds copper stably in human serum under physiological conditions. In contrast, other reagents based on ethylenediaminetetraacetic acid or diethylenetriaminepentaacetic acid rapidly lose copper to serum albumin under the same conditions. PMID- 4037306 TI - The use of guanidinium chloride in the preparation of stable cellular homogenates containing ATP. AB - Rat eye lenses were prepared for ATP determination by homogenization in 8 M guanidinium chloride-0.01 M EDTA. Standards of ATP were made up in the same solution. ATP appears to be quite stable in this solution in both standards and lens homogenates whether storage is at room temperature, 4 degrees C, or -20 degrees C for up to several weeks. ATP was measured using a luciferin-luciferase preparation in Hepes buffer, pH 7.75. The photons of light produced were detected by a bioluminescence counter. PMID- 4037307 TI - A microtiter plate assay for N-acetyl-beta-D-glucosaminidase using a fluorogenic substrate. AB - We describe a simple endpoint method for the determination of N-acetyl-beta-D glucosaminidase (NAGase; EC 3.2.1.30). NAGase uses a fluorogenic substrate, 4 methylumbelliferyl-N-acetyl-beta-D-glucosaminide, at pH 4.6, liberating the fluorescent 4-methylumbelliferone. The method is reproducible and fast both at room temperature and at 37 degrees C. The procedure developed can be used, e.g., in the diagnosis of bovine subclinical mastitis, where elevated NAGase activities are found in raw milk samples. The assay procedure has a high capacity and high sensitivity and several hundred milk samples can be screened per hour using 96 well microtiter plates and an automated fluorescence reader. In addition to its use in mastitis diagnosis, the assay can be used in the diagnosis of some diseases of human origin. PMID- 4037308 TI - In situ immunological determination of basic carbohydrate structures of gangliosides on thin-layer plates. AB - An immunological method for the determination of the basic carbohydrate structure of gangliosides by using a thin-layer chromatographic immunostaining technique was developed. After high-performance thin-layer chromatography of gangliosides, the chromatogram is treated with a 0.4% polyisobutylmethacrylate solution. Arthrobacter ureafaciens neuraminidase is then applied to the separated gangliosides in situ on the chromatographic plate. This procedure will remove both external and internal sialic acid residues from the core oligosaccharide backbone. The resulting glycolipid products are then incubated with anti-Gg4 serum and 125I-staphylococcal protein A, successively, and exposed to an X-ray film. Through a highly specific binding, the anti-Gg4 antibody detects only those gangliosides having the oligosaccharide backbone of Gg4. PMID- 4037309 TI - Assay of human fibrinopeptides by high-performance liquid chromatography. AB - Fibrinopeptides A, AP, and B, desarginine fibrinopeptide B, and a previously unknown peptide corresponding to B beta 3-14 were resolved within 10 min by an HPLC technique using an isocratic solvent system (22% acetonitrile in 0.1% trifluoroacetic acid) and a 0.46 X 10-cm Spherisorb ODS-2 (3-micron) octadecylsilane column. Fibrinopeptides A and AY eluted in the same peptide peak. The method was used to evaluate a carboxypeptidase which converts fibrinopeptide B into its desarginine form. Fifty percent inhibition of this activity occurred at 1.7 mM epsilon-aminocaproic acid (EACA). At saturating substrate concentrations the rates of total fibrinopeptides A and B release were unaffected by 125 mM EACA, a concentration at which the carboxypeptidase activity is completely inhibited. PMID- 4037310 TI - Analysis of erythrocyte protein methyl esters by two-dimensional gel electrophoresis under acidic separating conditions. AB - A two-dimensional polyacrylamide gel electrophoresis system which is suitable for the analysis of protein methylation reactions in cells incubated with L-[methyl 3H]methionine is described. The procedure separates proteins under primarily acidic conditions by isoelectric focusing in the first dimension and by sodium dodecyl sulfate electrophoresis at pH 2.4 in the second dimension. The low pH is essential for preserving protein [3H]methyl esters, but it limits the effective separating range of this system to proteins with isoelectric points between 4 and 8. With this system, we have shown that most, if not all, erythrocyte membrane and cytosolic proteins can act as substoichiometric methyl acceptors for an intracellular S-adenosylmethionine-dependent carboxyl methyltransferase and that protein carboxyl methylation reactions may be the major methyl transfer reaction in erythrocytes. These results are most consistent with the generation of protein substrate sites for the carboxyl methyltransferase by spontaneous deamidation and racemization reactions. PMID- 4037311 TI - Preparative elution of proteins from nitrocellulose membranes after separation by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. AB - Various conditions were analyzed and optimized for the preparative elution of proteins from nitrocellulose membranes after transfer from sodium dodecyl sulfate (SDS)-polyacrylamide gels. The efficiency of elution was best using pyridine or acetonitrile elution solvents, intermediate for buffer containing a mixture of sodium dodecyl sulfate, Triton X-100, and sodium deoxycholate, and negligible for buffers containing any single detergent or chaotropic salt, such as urea or guanidine hydrochloride. The efficiency of elution with any solvent also depended on the molecular weight of the proteins, smaller proteins being more easily removed from membranes. As a general procedure, proteins may be eluted from nitrocellulose membranes by incubation with either 40% acetonitrile or 50% pyridine in 0.1 M ammonium acetate, pH 8.9, for 1-3 h at 5-37 degrees C. The recommended procedures for protein elution appear to offer a rapid, simple, and efficient means of recovering proteins from complex mixtures after separation by SDS-PAGE and transfer to nitrocellulose membranes. PMID- 4037313 TI - 1985-1986 LabGuide. PMID- 4037312 TI - Isolation of protein S6 from rat liver ribosomes by reversed-phase high performance liquid chromatography. AB - A rapid procedure for the isolation of ribosomal protein S6 from rat liver ribosomes has been developed in which proteins were separated by reversed-phase HPLC using wide-pore n-butyl-, n-octyl-, or diphenyl-bonded silica phases. Rapid processing of whole ribosomal material was achieved by the extraction of proteins in 6 M guanidinium hydrochloride and subsequent precipitation of RNA by acidification. Highly purified S6 was obtained in two chromatographic steps as shown by sodium dodecyl sulfate-gel electrophoresis, amino acid analysis, and automated microsequencing. The purification of S6 was monitored using 32P-labeled S6 as a marker which cochromatographed with unphosphorylated S6 under the low-pH elution conditions employed. Other ribosomal proteins were also purified using these reversed-phase supports, although in the case of more hydrophobic proteins such as S4 and S10 further optimization of the gradient conditions was required. PMID- 4037314 TI - Fast atom bombardment and laser desorption mass spectrometry for determination of alkyltriphenylphosphonium salts. PMID- 4037315 TI - Tandem mass spectrometry with fast atom bombardment ionization of cobalamins. PMID- 4037316 TI - Investigations of a new sample compartment assembly for low-temperature and room temperature solid substrate phosphorimetry. PMID- 4037317 TI - Effects of acid type and concentration on the determination of 34 elements by simultaneous inductively coupled plasma atomic emission spectrometry. PMID- 4037318 TI - Gas chromatography/multiphoton ionization Fourier transform mass spectrometry. PMID- 4037319 TI - Solid sorbent for sampling of sulfur dioxide in occupational hygiene. PMID- 4037320 TI - Analysis of triglycerides in oils and fats by liquid chromatography with the laser light scattering detector. PMID- 4037321 TI - Multielement determination in biological materials by differential pulse voltammetry. PMID- 4037322 TI - Evaluation of robot automated drug dissolution measurements. PMID- 4037323 TI - Spectrophotometric determination of mercury in zinc blende and pharmaceutical preparations with 1-salicylidene-5-(2-pyridylmethylidene)isothiocarbonohy drazide. PMID- 4037324 TI - Reverse-phase high-performance liquid chromatography/nuclear magnetic resonance spectrometry separations of biomolecules with 1-1 hard pulse solvent suppression. PMID- 4037325 TI - Determination of iodine-131 at low concentrations in formaldehyde-preserved milk. PMID- 4037326 TI - Vacuum-tight thin-layer spectroelectrochemical cell with a doublet platinum gauze working electrode. PMID- 4037327 TI - In vitro measurement of dopamine concentration with carbon fiber electrode. PMID- 4037328 TI - Thin-layer electrochemical detector with a glassy carbon electrode coated with a base-hydrolyzed cellulosic film. PMID- 4037329 TI - Direct serum injection with micellar liquid chromatography for therapeutic drug monitoring. PMID- 4037330 TI - Liquid chromatographic determination of penicillins by postcolumn alkaline degradation. PMID- 4037331 TI - Hierarchical tree based storage, retrieval, and interpretation of infrared spectra. PMID- 4037332 TI - Californium-252 plasma-desorption mass spectrometry of polymethylenediamine linked enkephalin peptides. PMID- 4037333 TI - Electron spectroscopic (ESCA) studies of platinum surfaces used for enzyme electrodes. PMID- 4037334 TI - Identification of polyaromatic hydrocarbon mixtures by low-temperature constant energy synchronous fluorescence spectrometry. PMID- 4037336 TI - Influence of laboratory environment on the precision and accuracy of trace element analysis. PMID- 4037335 TI - Least squares singular value decomposition for the resolution of pK's and spectra from organic acid/base mixtures. PMID- 4037337 TI - Photoelectroanalytical chemistry: electrochemical detection of a photochemically active species, tris(2,2'-bipyridine)ruthenium(II). PMID- 4037338 TI - Dehalogenation reactions in californium-252 plasma desorption mass spectrometry. PMID- 4037339 TI - Improved on-line stripping voltammetry using a large volume wall-jet detector. PMID- 4037340 TI - Fast in vivo monitoring of dopamine release in the rat brain with differential pulse amperometry. PMID- 4037341 TI - Chemical tests for intoxication: what do the numbers really mean? PMID- 4037342 TI - Sensitive detection of biacetyl in liquid chromatography using time-resolved sensitized phosphorescence. PMID- 4037343 TI - Particle counting by laser light scatter for capillary hydrodynamic chromatography. PMID- 4037344 TI - pH-based enzyme potentiometric sensors. Part 1. Theory. PMID- 4037345 TI - pH-based enzyme potentiometric sensors. Part 2. Glucose-sensitive field effect transistor. PMID- 4037346 TI - pH-based enzyme potentiometric sensors. Part 3. Penicillin-sensitive field effect transistor. PMID- 4037347 TI - Isolation and characterization of cysteine-containing regions of proteins using 4 (aminosulfonyl)-7-fluoro-2,1,3-benzoxadiazole and high-performance liquid chromatography. PMID- 4037348 TI - Determination of trimethylselenonium ion in urine by ion-exchange chromatography and molecular neutron activation analysis. PMID- 4037349 TI - Applications of a slotted quartz tube and flame atomic-absorption spectrometry to the analysis of biological samples. PMID- 4037350 TI - Optimisation of the analytical conditions for the determination of aluminium in human blood plasma or serum by graphite furnace atomic-absorption spectrometry. Part I. Examination of the various analytical conditions. PMID- 4037351 TI - Determination of lithium, rubidium and strontium in foodstuffs. PMID- 4037352 TI - Camera luminometer for use with luminescent assays. PMID- 4037353 TI - Fluorescence and chemiluminescence determination of steroid and bile acid sulphates with lucigenin by flow injection analysis based on ion-pair solvent extraction. PMID- 4037354 TI - Determination of albumin with bromocresol purple using controlled-dispersion flow analysis. PMID- 4037355 TI - Evaluation of methods for the determination of total molybdenum and vanadium in foodstuffs using spectrophotometric measurements. PMID- 4037356 TI - Determination of chlorine dioxide in potable waters using chlorophenol red. PMID- 4037357 TI - Spectrophotometric determination of zinc with biacetyl mono(2-pyridyl)hydrazone with application to its determination in tap waters and in alkali and alkaline earth metal chemicals. PMID- 4037358 TI - Titrimetric determination of dipyrone and paracetamol with potassium hexacyanoferrate(III) in an acidic medium. PMID- 4037359 TI - Spectrophotometric determination of salicylic acid in pharmaceutical formulations using copper(II) acetate as a colour developer. PMID- 4037360 TI - Determination of a range of organophosphorus pesticide residues in grain. Committee for Analytical Methods for Residues of Pesticides and Veterinary Products in Foodstuffs and the Working Party on Pesticide Residues of the Ministry of Agriculture, Fisheries and Food. PMID- 4037361 TI - Determination of cephalosporins utilising thin-layer chromatography with fluorescamine detection. PMID- 4037362 TI - Determination of griseofulvin, carvone and menthone through intermediate oxime formation. PMID- 4037363 TI - Spectrophotometric determination of ascorbic acid and thiamine hydrochloride in pharmaceutical products using derivative spectrophotometry. PMID- 4037364 TI - Determination of cardiac glycosides by adsorptive stripping voltammetry. PMID- 4037365 TI - Quantification of results for estimating elemental dietary intakes of lithium, rubidium, strontium, molybdenum, vanadium and silver. PMID- 4037366 TI - Fluorimetric determination of baclofen [gamma-amino-beta-(p-chlorophenyl)butyric acid]. PMID- 4037367 TI - From sensory periphery to cortex: the architecture of the barrelfield as modified by various early manipulations of the mouse whiskerpad. AB - The barrelfield is the cortical "map" of the ensemble of vibrissal follicles on the mouse whiskerpad. Earlier, we had shown that the skin of the embryonic whiskerpad, when put in culture before having received its innervation, is capable of producing vibrissal follicles arranged in a pattern similar to that formed in vivo; we had also demonstrated that the destruction of vibrissal follicles, and of the terminals that innervate them, leads to important modifications in the architecture of the barrelfield. Here we report on the architecture of barrelfields made to differ from normal as a consequence of radical modifications produced in the corresponding whiskerpad during gestation and at birth: transplantation of additional whiskerpads; rotations (of 90 degrees and 180 degrees) of one whiskerpad; removal and reimplantation of one whiskerpad; removal of one whiskerpad; and division of the infraorbital nerve. The results of these experiments, in which only the morphological correlates of a sensory cortical map have been studied, strengthen the hypothesis that the role played by the sensory periphery in the establishment of such an entity is, indeed, an important one. PMID- 4037368 TI - Embryonic development of the mouse mutant pupoid foetus (pf/pf). AB - The pupoid foetus mutation in the mouse is a recessive lethal mutation causing death of homozygous (pf/pf) embryos immediately after birth. From 11.3 days gestation onwards, these embryos are characterised externally by the development of a tail twist, followed by apparent stunting of the limbs and tail (when compared with the development of these structures in normal embryos), lack of digits, distortion of facial features, and possession of a smooth, mottled skin. Embryos ranging in age from 11.3 days gestation to full term have been examined using light microscopy and scanning and transmission electron microscopy. The skeletal structure and internal organs of the embryo are normal, but abnormalities occur in the external epidermis, the dermis, and the peripheral sensory nerves. Development of the palate and the eyes are affected by the behaviour of these tissues. The epidermis undergoes hypertrophy and fails to differentiate, and, on the basis of morphological criteria and theoretical considerations, it is suggested that the pf gene is activated in the epidermis during the keratinization pathway, preventing differentiation and altering the cell surface characteristics of the cells. Other abnormalities are explained in terms of interactions with the epidermis. This mutant is compared with other similar mutants. PMID- 4037369 TI - The pig mesonephros. III. Distal tubule, collecting tubule, and Wolffian duct: SEM- and TEM-studies. AB - The ultrastructure of the distal and collecting tubules of mature pig mesonephroi (41st gestational day) was studied in perfusion-fixed embryos. In the distal tubule, the three subsegments postulated on the basis of enzyme histochemistry show only minor differences of their luminal surfaces, mostly of cell size. TEM photographs reveal a single cell type with interdigitating basolateral processes, frequently flattened to 30-120 nm lamellae devoid of organelles. Larger interdigitating processes harbor vertically oriented mitochondria in the form of indented plates. The macula densa cells are small, do not interdigitate, and have distended intercellular spaces. The collecting tubule starts with a dorsal convolution, in which intercalated cells (with apical microfolds and numerous mitochondria) occur in addition to interdigitating cells. Further down this segment, the interdigitating cells are gradually replaced by principal cells characterized by interlocking lateral microvilli, basal infoldings, and relatively few organelles. Intercalated cells extend into the Wolffian duct. Although the pig mesonephros has the most differentiated nephron of the mammals studied so far, with metanephros-like cells, its intrinsic urinary concentrating capacity appears to be low in view of its vascularization pattern and nephron architecture. PMID- 4037370 TI - The ultrastructure of early cephalic neural crest cell migration in the mouse. AB - A study of the ultrastructural changes associated with the detachment of the presumptive neural crest cells from the neuroepithelium in the midbrain region in mouse embryos at 9 and 9 1/2 days of gestation was carried out. The first sign of neural crest cell formation occurred in this region before fusion of the neuroepithelium had occurred. Neural crest cells arose from both the neural plate and the adjoining surface ectoderm. Initially, the cells of the neural plate and the surface ectoderm were attached to each other by zonula occludens and zonula adherans at their apical surfaces however, these junctions disappeared just prior to the beginning of the migration of the crest cells. The first sign of migration of the crest cells was the disappearance of the basal lamina in the region of the presumptive crest cells. Once the basal lamina was lost, cell junctions were formed between the epithelial cells and the underlying mesenchymal cells. Once the crest cells had migrated into the underlying mesenchyme, they tended to form clumps of closely related, irregularly shaped cells. Phagosomes and accumulations of glycogen particles were found within some crest cells when they were still within 50 to 100 microns of the epithelium. PMID- 4037371 TI - On the ontogenetic development of the rat dorsal lateral geniculate nucleus. I. GCR-neurons at postnatal day 7--a Golgi-electron microscopic study. AB - The morphology and synaptic input of four geniculo-cortical relay neurons of albino rats of postnatal day (PD) 7 has been studied with light and electron microscopy, utilizing the combined Golgi-EM technique. Although the nerve cells investigated did show a characteristic relay-cell appearance of the adult, certain dendritic structures exhibited immature character. These were the dendritic swellings, or "growth buds" occurring throughout the whole length of the dendrites, but particularly along the segments and at bifurcations of thin distal dendritic portions. These dendritic thickenings together with the transient spine-like hairy processes were seen to receive many synaptic endings of various developmental stages. The majority of synaptic junctions both on the dendritic swellings and on dendritic shafts were of the asymmetric type. Contrary to our expectation, no proximo-distal gradient could be demonstrated in the maturation of axodendritic synapses, at least not during the first synaptogenetic period, i.e., at PD 7. Also, all axosomatic synapses in the PD7 rat LGNd were asymmetric, indicating that the replacement of asymmetric synapses by symmetric ones (characteristic for the adult stage) occurs only after the first synaptogenetic period. The rarity of Gray II type, symmetric contacts during the early synaptogenesis (i.e., at PD 7) explains the absence of triadic, or serial synapses which will develop only later, during the second synaptogenetic period. PMID- 4037372 TI - The influence of stress and strain in the early development of shaft bones. An experimental study on the chick embryo tibia. AB - In chick embryos from stage 23 to stage 27 the whole presumptive zeugopod - or its pre-axial (tibial) portion only - was proximodistally and dorsoventrally inverted by turning it 180 degrees round the anteroposterior axis of the limb bud. Development of the reoriented blastema of the tibia was consistently retarded and variously reduced: this skeletal piece appeared shorter and relatively thicker than the controlateral normal tibia. Chondrification, progress of differentiation of the cartilaginous model, onset and gradual spreading of the ossification processes were considerably delayed. Often the diminutive tibia underwent a degree of bending or angulation of up to 90 degrees - 100 degrees in the sagittal plane. In these bent tibiae - obviously developing under abnormal conditions of intrinsic and extrinsic mechanical stresses - cell hypertrophy appeared greatly retarded or hindered in sites of the diaphysial cartilaginous core which were presumably subjected to strong longitudinal compression. No rigorous temporal and topographical relationships were observed between chondrocyte hypertrophy and onset of perichondral osteogenesis. Apparently, a direct contact between hypertrophic cartilage and perichondrial cells was not strictly required to prompt osteogenesis; this process, in fact, often involved areas of the perichondrium enveloping parvicellular cartilage. Radial pressures exerted by the over-stretched outer layer of the perichondrium, or periosteum, on the subjacent prospective osteogenous layer reduced or prevented the deposition of bone. Conversely, radial stretching of the inner layer of the perichondrium, or periosteum, considerably enhanced cell proliferation, blood vessel formation, differentiation of osteoblasts and formation of bone matrix. PMID- 4037373 TI - The surface anatomy of the human aortic valve as revealed by scanning electron microscopy. AB - The anatomy of the human aortic valve was studied by SEM in 36 subjects without cardiac pathology who had died of various accidental causes. Villous and lamellar tissue excrescences were observed at the node of Arantius and at the limit between the lunules and the load-bearing portion of the leaflets. The morphology of these structures suggests that they represent areas in which valve tissue becomes detached into the bloodstream. Fenestrations were present in the lunules of 14 specimens, with a higher incidence in specimens from subjects who were middle-aged or older. Our observations suggest that fenestrations appear initially as small perforations which then coalesce to form larger apertures. Two main types of endothelial cells, elongated and polygonal were detected on the endothelial surface of the leaflets. Both types of cells display a constant mode of arrangement on the different segments of the leaflets (lunules, node of Arantius and load-bearing portion of the leaflet). The possible relationships between endothelial cell morphology and the pattern of mechanical stress to which the leaflets are subjected is discussed. PMID- 4037374 TI - Differentiation of extracellular matrix in the cellular cartilage ("Zellknorpel") of the mouse pinna. AB - Differentiation of cellular cartilage was studied in the mouse pinna with particular reference to matrix material. Fixation of glycosaminoglycans was performed by the use of acridine orange and elastin was identified by staining thin sections with tannic acid and uranyl acetate. Condensation of mesenchymal cells ("prechondroblasts") initiates the formation of a blastema of cartilaginous tissue at postnatal day 4. The synthesis of acidic glycosaminoglycans begins at postnatal day 8 when prechondroblasts transform to chondroblasts. Glycosaminoglycans can be detected within secretory vesicles of chondroblasts at postnatal day 8, in the extracellular space at postnatal day 13. Delicate collagen fibrils and elastic fiber microfibrils are seen between prechondroblasts and chondroblasts. Deposition of elastin begins at postnatal day 11. A network of elastic fibers and lamellae is formed, which replaces both collagen fibrils and elastic fiber microfibrils. In the interstice of mature cellular cartilage only elastin and proteoglycans are present (postnatal day 21). These findings indicate that cellular cartilage represents an independent kind of supporting tissue, which may serve as a progenitor of hyaline or elastic cartilage ("transitional cellular cartilage") but does not differentiate from hyalin cartilage. PMID- 4037375 TI - The vagina is formed by downgrowth of Wolffian and Mullerian ducts. Graphical reconstructions from normal and Tfm mouse embryos. AB - We use the Tfm (testicular feminization) mutation of the mouse to reexamine the role of Wolffian and Mullerian ducts during formation of the vagina. Three dimensional graphical reconstructions of the lower genital tract are prepared from serial sections of male, female, and Tfm embryos from day 15 p.c. until 8 days after birth. The reconstructions show that in female and Tfm animals the caudal segments of Wolffian and Mullerian ducts fuse and migrate caudally, whereas in the male they do not fuse and remain in their original position. Following down-growth, separate Wolffian and Mullerian ducts emerge from the fused caudal tips of the ducts. The Wolffian ducts degenerate, while the Mullerian ducts fuse with each other and form the vagina. Wolffian and Mullerian ducts are connected to the urogenital sinus by the sinus ridges which in later stages are separated from the sinus by lateral furrows. The sinus ridges are replaced by the Mullerian ducts. We conclude that the vagina develops by down growth of Wolffian and Mullerian ducts along the sinus ridges. Wolffian ducts and sinus ridges regress so that the definitive vagina is formed by the Mullerian ducts. In Tfm embryos the vagina forms as in the female but subsequently degenerates, probably due to the action of AMH. The vaginal pocket in the Tfm is the variable remainder of the vagina at the end of the degeneration process. PMID- 4037376 TI - Nonparenchymal liver cells in a vertebrate without bile ducts. AB - The nonparenchymal portion of the liver of parasitic adult lampreys (Petromyzon marinus L.) consists of endothelial, Kupffer, fibroblast-like, fat-storing, and granulated cells. The fenestrae of endothelial cells are not organized into sieve plates but are of highly variable size and distribution. The dimension of some fenestrae suggests the possible transport of substances of large molecular size. Small numbers of Kupffer cells possess many features of these cells observed in other vertebrates but they do not have worm-like bodies and endogenous peroxidase activity. They are involved in erythrophagocytosis and perhaps the ingestion of other foreign material but they do not store iron. Fat-storing and fibroblast like cells share many morphological features and may be different expressions of the same cell type. These perisinusoidal cells are rich in organelles suggesting protein synthesis but the fibroblast-like cells lack fat droplets. A cell with a large Golgi apparatus and associated cytoplasmic granules resembles the pit cell described in the liver of a few other vertebrates. The morphology of nonparenchymal cells of the liver in parasitic adult lampreys does not reflect the absence of bile ducts in this organism. PMID- 4037378 TI - Intracranial pressure during diltiazem-induced hypotension in anesthetized dogs. AB - The effect of diltiazem-induced hypotension on intracranial pressure (ICP) was studied in dogs with normal and elevated ICP. Eight dogs were anesthetized with intravenous pentobarbital, intubated, and ventilated with N2O:O2. Mean arterial pressure (MAP), heart rate (HR), pulmonary artery pressure (PAP), pulmonary capillary wedge pressure (PCWP), central venous pressure (CVP), and cardiac out put (CO) were recorded. A ventriculostomy was performed for measurement of ICP. Baselines were established, and diltiazem was infused to reduce MAP 40 +/- 1% for 10 min. After recording the effects of diltiazem-induced hypotension during normal ICP, ICP was elevated by infusion through a ventriculostomy cannula of pH adjusted Ringer's lactate, baselines were reestablished, and MAP was again reduced by 40 +/- 1% with diltiazem. When baseline ICP was normal, diltiazem induced hypotension produced a statistically significant increase in ICP (4.8 +/- 0.6 mm Hg) and a decrease in cerebral perfusion pressure (CPP). When baseline ICP was elevated, a smaller increase in ICP occurred (1.3 +/- 0.5 mm Hg). Although these increases in ICP were not clinically significant, the dose of diltiazem required to lower MAP 40% caused significant alterations in HR, systemic vascular resistance, CO, and PCWP. Serious cardiac rhythm disturbances occurred in five of eight dogs when baseline ICP was normal and in six of eight dogs when baseline ICP was elevated. The relatively long duration of diltiazem's hemodynamic effect and the high incidence of cardiac rhythm disturbances make it an unsuitable drug for inducing deliberate hypotension. PMID- 4037377 TI - Absence of filipin-sterol complexes from the ciliary necklace of ependymal cells. AB - The polyene antibiotic filipin reacts specifically with membrane cholesterol and produces membrane perturbations. Prefixed vibratome slices of cat ependymal cells were treated with a glutaraldehyde solution containing 300 microM filipin. Freeze fracture of these cells revealed numerous 25-30 nm protuberances on fracture faces (filipin-sterol complexes) in the ciliary membrane. In the ciliary necklace, however, these filipin-sterol complexes were absent. These results suggest that the ciliary necklace has a low cholesterol content. PMID- 4037379 TI - Comparative effects of halothane, enflurane, and methoxyflurane on the incidence of abnormal development using sea urchin gametes as an in vitro model system. AB - The incidence of sea urchin embryos developing abnormally after their exposure to equimolar concentrations of halothane, enflurane, and methoxyflurane has been determined. Halothane concentrations in the 0.6-1.25 mM range caused 18-96% of the embryos to undergo abnormal cleavage at the first cell division. This is important because embryos exhibiting atypical cleavage patterns at the first cell division eventually involute and die before reaching gastrulation. Over the same range of concentrations, enflurane and methoxyflurane have minimal effects on development. However, when exposed to 2.5 mM methoxyflurane, nearly 40% of the cells did not fertilize. These results show that volatile anesthetic agents have decidedly different effects on development and suggest that the incidence of abnormal development may not correlate directly with the anesthetic potency of inhalational agents. PMID- 4037380 TI - Inflation device to prevent aortocaval compression during pregnancy. PMID- 4037381 TI - A single-unit device for differential lung ventilation with only one anesthesia machine. PMID- 4037382 TI - Subdural migration of an epidural catheter. PMID- 4037383 TI - Much ado about nothing: trace gaseous metabolites in the closed circuit. PMID- 4037384 TI - Surgically induced hypertension in brain dead patients. PMID- 4037385 TI - Movement of the distal end of the endotracheal tube during flexion and extension of the neck. PMID- 4037386 TI - A simple method for improving the safety of percutaneous cannulation of the internal jugular vein. PMID- 4037387 TI - Thoughts on protamine toxicity. PMID- 4037388 TI - Ketamine for treatment of priapism. PMID- 4037389 TI - Aminophylline antagonism of the residual effects of fentanyl anesthesia. PMID- 4037390 TI - Myoclonus after etomidate anesthesia. PMID- 4037391 TI - Common sense in statistical analyses. PMID- 4037392 TI - Precautions in use of a new endotracheal tube for laser surgery. PMID- 4037393 TI - Anesthesia-related transient aphonia and quadriplegia. PMID- 4037394 TI - Halothane and isoflurane do not decrease PaO2 during one-lung ventilation in intravenously anesthetized patients. AB - We examined the effect of the inhalational anesthetics halothane (H) and isoflurane (IF) on arterial oxygenation during one-lung ventilation. Twenty consenting patients who required thoracotomy and one-lung ventilation were initially anesthetized only with the intravenous agents, diazepam, fentanyl, pancuronium, metocurine, and infusions of either ketamine or methohexital. A double lumen endotracheal tube was inserted, and each patient's lungs were mechanically ventilated (two-lung ventilation, step 1) with 100% O2 while the patient was in the lateral decubitus position. After the pleura was opened, the nondependent lung was collapsed while the dependent lung continued to be ventilated with 100% O2. After serial PaO2 measurements indicated achievement of stable one-lung ventilation conditions (step 2), intravenous anesthetic agents were discontinued, and either H (n = 10) or IF (n = 10) was administered (step 3) so that PETH = 7.70 +/- 0.61 mm Hg and PETIF = 9.89 +/- 1.08 mm Hg for more than 15 min; at the end of step 3, PaH/PETH = 0.82 (n = 5), PaIF/PETIF = 0.75 (n = 5), PvH/PETH = 0.64 (n = 3), and PvIF/PETIF = 0.68 (n = 3). The inhalational anesthetics were then discontinued, and intravenous agents were reinstituted, allowing PETH and PETIF to decrease below 0.50 mm Hg (step 4). Two-lung ventilation was resumed at the end of the surgical procedure (step 5). PaO2 decreased from 441 +/- 64 to 252 +/- 70 mm Hg when one-lung ventilation was achieved (steps 1-2), and PaO2 increased from 258 +/- 72 to 395 +/- 65 mm Hg when two-lung ventilation was resumed (steps 4-5).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4037395 TI - Comparison of the requirements for hepatic injury with halothane and enflurane in rats. AB - A rat model of enflurane-associated hepatotoxicity was compared with the halothane-hypoxia (HH) model (adult male rats, phenobarbital induction, 1% halothane, 14% O2, for 2 hr). The enflurane-hypoxia heating (EHH) model involved exposing phenobarbital-pretreated male adult rats to 1.5-1.8% enflurane at 10% O2 for 2 hr with external heating to help maintain body temperature. Exposure to either anesthetic without temperature support led to a decrease in body temperature of 7-9 degrees C, while heating the animals during anesthesia resulted in only a 0.5-2 degree decrease. Reducing the oxygen tension to 10% O2 combined with heating the animals during exposure produced significant decreases in the oxidative metabolism of both halothane and enflurane as compared to exposures of 14% O2. The same conditions also caused a significant increase in the reductive metabolism of halothane, indicating that a severe hepatic hypoxia or anoxia occurs during anesthesia at 10% O2 with external heating. The time course of lesion development in the HH model paralleled results obtained with an oral dose of CCl4: gradual progression of necrosis up to 24 hr. EHH resulted in a classic hypoxic/anoxic injury with elevated serum glutamate pyruvate transaminase values and a watery vacuolization of centrilobular hepatocytes immediately after exposure. The HH model required phenobarbital pretreatment of the rats for expression of hepatic injury; EHH did not. Heating of the animals during anesthesia exposure was necessary for enflurane-induced hepatoxicity but had little effect on the HH model. Exposure to 5% O2 without anesthetic mimicked EHH in both requirements for and type of hepatic injury. PMID- 4037396 TI - Hospitalization for miscarriage and delivery outcome among Swedish nurses working in operating rooms 1973-1978. AB - All infants born in 1973-1978 to nurses working in anesthesiology or as operating room nurses were identified from a nationwide registry of all births in Sweden, a registry of hospitalized spontaneous and legally induced abortions that covers 70% of Sweden, and a nurse registry (n = 1323). For comparison, a group was formed that consisted of nurses working in medical wards (n = 1382). Delivery outcome was also compared with the estimate expected from nationwide figures. No statistically significant differences were seen, but infants of the anesthesiology/operating room nurses had a slightly higher perinatal death rate and a slightly higher rate of preterm births and low birth weights than infants in the comparison group and the nationwide average. On the other hand, the malformation rate was lower in the infants of anesthesiology/operating room nurses than in the control group or nationwide average. A case-control study within the group of anesthesiology/operating room nurses was performed. Questionnaires were sent to 75 nurses (25 cases whose infants died or had serious malformations; 50 controls whose infants were normal); 74 responded. The only difference in working conditions for cases and controls was that the cases had worked after the twenty-eighth week of pregnancy more often than the controls. However, this finding was restricted to nurses whose infants were malformed, and work after the twenty-eighth week cannot affect malformation rate. Work in anesthesiology or operating rooms had no effect on the incidence of hospitalization for miscarriage, perinatal deaths, or malformations detected in the neonatal period. PMID- 4037397 TI - Control and accountability of controlled substance administration in the operating room. AB - Personnel working in the operating room complex may be at increased risk for chemical impairment. It has been proposed that this predisposition may be related to the frequency of use of controlled substances and the inadequate control over distribution of these medications, which frequently exists in the operating room. A system utilizing a pharmacy satellite in the operating room has increased the control and accountability of drug administration practices. Several other alternative systems are also reviewed. Emphasis is placed on the establishment of a quality assurance program to monitor compliance routinely. PMID- 4037398 TI - Comparison of the effects of general and regional anesthesia for cesarean section on neonatal neurologic and adaptive capacity scores. AB - Fifty-two neonates delivered by elective cesarean section were evaluated using the Neonatal Neurologic and Adaptive Capacity Scores. Twenty of the mothers received general anesthesia, 14 received epidural, and 18 received spinal anesthesia. All mothers receiving regional anesthesia were prehydrated with 1000 ml of lactated Ringer's solution and were given oxygen via a transparent face mask. All mothers undergoing general anesthesia received thiopental for induction followed by N2O-O2 (4 L:4 L) and 0.5% enflurane until delivery of the baby. All mothers were healthy, not in labor, and were scheduled for elective cesarean section. All neonates weighed 2500 g or more, had Apgar scores of 7 or more at 1 and 5 min, and had normal acid base and blood gas data. Neonates delivered with general anesthesia scored significantly lower on some of the test items for adaptive capacity, passive tone, active tone, primary reflexes, and total scores at both 15 min and 2 hr of age (P less than 0.05) than those delivered with either epidural or spinal anesthesia. Neonates delivered with epidural anesthesia scored lower than those delivered with spinal anesthesia on supporting reaction and motor activity at 2 hr of age (P less than 0.05). All neonates had high scores at 24 hr, at which time there were no significant differences between the three groups. PMID- 4037399 TI - Effect of halothane on renal hemodynamics during normovolemia and acute hemorrhagic hypovolemia. AB - The effects of halothane on renal hemodynamics under both normovolemic and hypovolemic conditions were investigated in chronically instrumented conscious dogs whose homeostatic mechanisms were not altered by the presence of preexisting drugs. Renal blood flow and aortic pressure were assessed by prior implantation of Doppler ultrasonic flow probes on the renal artery and a catheter in the descending aorta. Administration of halothane to conscious normovolemic dogs (Group HN) resulted in 11-26% decreases in renal vascular resistance with no significant changes occurring in renal blood flow. In a second group of animals made hypovolemic while awake (Group AH), 30% of the blood volume was removed over one-half hour. In response to hemorrhage, these conscious animals' renal blood flow did not significantly change from the normovolemic control, and renal vascular resistance significantly decreased. With no further intervention, renal vascular resistance and renal blood flow remained unchanged from the level achieved after the 30% hemorrhage. A third group of animals (Group HH) was hemorrhaged in a manner similar to that of Group AH. They also showed no significant changes in renal blood flow and a significant decrease in renal vascular resistance in response to hemorrhage. Thereafter, administration of halothane, as in Group HN, to this group produced 11-23% decreases in renal vascular resistance with no significant decline in renal blood flow from the hypovolemic control levels established after hemorrhage. The author concludes the following: administration of halothane to normovolemic conscious dogs does not decrease renal blood flow; a moderate degree of acute hemorrhagic hypovolemia does not decrease renal blood flow in conscious dogs; and administration of halothane to acutely hypovolemic conscious dogs does not impair renal perfusion. PMID- 4037400 TI - Bicitra (sodium citrate) and metoclopramide in outpatient anesthesia for prophylaxis against aspiration pneumonitis. AB - To evaluate the effect of Bicitra (Willen Drug Company, Baltimore, Maryland), a commercial preparation of sodium citrate and metoclopramide, on gastric contents 150 elective outpatients allocated into six groups with 25 patients in each group were studied. Patients in Group 1 served as controls. Patients in Groups 2, 3, 5, and 6 received Bicitra, po, either 15 ml (Groups 2 and 5) or 30 ml (Groups 3 and 6). In addition, patients in Groups 5 and 6 also received metoclopramide 10 mg, iv; Group 4 patients received metoclopramide 10 mg, iv. Eighty-eight per cent of patients in the control group had a gastric pH less than or equal to 2.5, while 36% had a gastric content volume greater than or equal to 25 ml with pH less than or equal to 2.5. Bicitra, 15 ml and 30 ml, po, increased mean gastric pH and decreased the proportion of patients with a gastric pH less than or equal to 2.5 to 32 and 16%, respectively, in Groups 2 and 3. However, Bicitra 15 ml and 30 ml, increased the mean gastric volume in Group 3 and also increased the proportion of patients with a gastric volume greater than or equal to 25 ml to 56% in Group 2 and 84% in Group 3. The addition of metoclopramide 10 mg, iv, to Bicitra reduced the proportion of patients with a gastric volume greater than or equal to 25 ml in Groups 5 and 6 to 28 and 36%, respectively. Metoclopramide (Group 6) independently reduced mean gastric volume (15.6 ml vs. 32.7 ml) and the proportion of patients with a gastric volume greater than or equal to 25 ml (20% vs. 36%). Bicitra and metoclopramide combination significantly reduced the proportion of patients with gastric contents greater than or equal to 25 ml with pH less than or equal to 2.5. PMID- 4037401 TI - Toxicity and resuscitation in lidocaine- or bupivacaine-infused cats. AB - Controversy persists surrounding the relative safety of bupivacaine compared with lidocaine especially with regard to its cardiovascular toxicity and the ability to resuscitate following such occurrences. The margin of safety between seizure onset and cardiovascular collapse was compared in lightly anesthetized and ventilated cats given an equipotent infusion of either lidocaine or bupivacaine (N = 10 for each group). The infusion rates were 4 mg X kg-1 X min-1 bupivacaine or 16 mg X kg-1 X min-1 lidocaine. Onset of electrical seizure activity occurred at about the same time in both groups and was defined as the central nervous system (CNS) toxic end point. The infusion continued until the mean arterial pressure reached 10 mmHg (cardiotoxic end point). Despite the early occurrence of electrocardiographic changes in the bupivacaine group, mean arterial pressure was greater and sustained significantly longer (4.9 +/- 1.3 min; mean +/- SD) with this drug compared with lidocaine (3.0 +/- 0.6 min) (P less than 0.005). Using the blood pressure criterion for defining cardiovascular (CV) collapse, the CV/CNS toxicity ratio for drug dosage was 4.0 with lidocaine and 4.8 with bupivacaine. The use of a standardized resuscitation protocol made it possible to compare the ability to resuscitate animals in each group. Despite very high plasma local anesthetic concentrations, all lidocaine-infused animals were quickly resuscitated (4.4 +/- 3.0 min; mean +/- SD). The resuscitation time for the bupivacaine group (5.4 +/- 2.4 min) was similar. Two cats in the bupivacaine group could not be brought to resuscitation criterion, a difference, however, that was not statistically significant. PMID- 4037402 TI - Local application of 133Xenon for measurement of regional cerebral blood flow (rCBF) during halothane, enflurane, and isoflurane anesthesia in humans. AB - It is well known that halothane causes an increase in cerebral blood flow (CBF). In this study the effects of halothane, enflurane, and isoflurane on regional cerebral blood flow (rCBF) in humans were determined in the presence of 70% N2O at a combined MAC concentration of 1.5. CBF was determined in 24 patients from the washout of locally applied 133Xenon with the use of an external scintillation. All 24 patients (control n = 6, halothane n = 6, enflurane n = 6, and isoflurane n = 6) were undergoing neurosurgical procedures. All patients were anesthetized with thiopental, fentanyl, droperidol, and 70% N2O in oxygen and paralyzed with pancuronium. The measurements were performed after the dura had been opened and before definitive surgery. The first measurement was done in the absence of any volatile agent, and the wash-out curve was registered for 6 min. The second measurement was done after one of the volatile agents had been added for at least 20 min and had reached a concentration of 0.58% for halothane, 1.14% for enflurane, or 1.0% for isoflurane in the expiratory gases in order to obtain about 1.5 MAC with each volatile anesthetic. The anesthetic concentrations were measured with the Engstrom multigas analyzer EMMA. The physiologic variables changed very little throughout the period of observation. Body temperature, heart rate, blood pressure, PaCO2, and PaO2 were stable. Ephedrine was used to maintain a stable arterial pressure. At approximately 1.5 MAC, halothane (plus N2O) increased rCBF to nearly three times (166%) the control value, while enflurane induced only a slight increase (35%) in rCBF.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4037403 TI - Responses of recurrent laryngeal, hypoglossal, and phrenic nerves to increasing depths of anesthesia with halothane or enflurane in vagotomized cats. AB - In order to compare the responses to increasing depths of anesthesia with inhalational anesthetic agents of the phrenic nerve and cranial nerves supplying upper airway muscles, the effects of acute administration of halothane (2.5%) or enflurane (5.0%) on the activities of the hypoglossal nerve (HN), the recurrent laryngeal nerve (RLN), and the phrenic nerve (PN) were investigated in artificially ventilated, vagotomized cats. Following administration of halothane or enflurane, rhythmic inspiratory activities of all three nerves decreased progressively, but the decrease in HN activity was more pronounced than the decreases in HN and RLN activities. During the course of respiratory depression due to increasing depth of anesthesia with halothane or enflurane, rhythmic inspiratory activities of PN and RLN decreased linearly and approximately at the same rate, indicating that the response of RLN more closely resembles that of PN. However, at a relatively deep level of anesthesia, rhythmic inspiratory RLN activity was replaced by strong tonic RLN activity, while PN activity was completely abolished, causing quantitatively and qualitatively different responses of RLN and PN. These peculiar responses of RLN activity to increasing depth of anesthesia were examined in more detail with the use of single- or few fiber preparations. Increasing depth of anesthesia depressed the inspiratory RLN units while recruiting other units, originally silent, indicating that there are two different groups of fibers in RLN whose response to increasing depth of anesthesia is exactly opposite to one another.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4037404 TI - Tactile and visual evaluation of the response to train-of-four nerve stimulation. PMID- 4037405 TI - Cricoid compression is effective in obliterating the esophageal lumen in the presence of a nasogastric tube. PMID- 4037406 TI - Bupivacaine in children: pharmacokinetics following caudal anesthesia. PMID- 4037407 TI - Chylothorax following celiac plexus block. PMID- 4037408 TI - Two-stage fiberoptic nasotracheal intubation in infants: a new approach to difficult pediatric intubation. PMID- 4037409 TI - Heel sores in association with prolonged epidural analgesia. PMID- 4037410 TI - An even simpler way to determine drug infusion rates. PMID- 4037411 TI - Concerning the acceptability of awareness during surgery. PMID- 4037412 TI - Health experiences of operating room personnel. PMID- 4037413 TI - Can traditional intubation be modified? PMID- 4037414 TI - Airway obstruction with esophageal monitors in a patient with double aortic arch. PMID- 4037415 TI - Reversibility of muscular ischemia: a histochemical quantification by the nitroblue tetrazolium (NBT) test. AB - The degree of muscular ischemia and its reversibility can be quantified in the early stages. This histochemical enzymatic study utilized Nitroblue tetrazolium (NBT) which when reduced by tissue dehydrogenase produces a blue pigment: "formazan." Seventy Wistar rats were subjected to transient hindlimb ischemia by means of a tourniquet for 3, 6, 9, 12, 15 and 18 hours, followed by reperfusion. Microsurgical muscle biopsies were obtained in each rat at 1 and 12 hours, and 3, 7, 14 days after reperfusion. Time increased in muscle staining demonstrated a succino-dehydrogenase deficit confirmed by clinical and histopathological follow up. NBT staining time was 2 minutes (+/- 8 sec.) in the control group, between 2 and 6 minutes in the reversible ischemia group (rats with 3 and 6 hours of tourniquet), and more than 9 minutes (+/- 14 sec.) in the irreversible ischemia group (animals with more than 9 hours of tourniquet). In vascular surgery and in limb reimplantation this protocol is a practical method of evaluating cytoplasmic enzymatic activity and the status of myofibrillar oxidation in the early phases of ischemic injury, before histologic changes are clearly delineated. PMID- 4037416 TI - Bone marrow status of anaemic pregnant women on supplemental iron and folic acid in a Nigerian community. AB - The bone marrow status of 31 consecutive pregnant women who had been on supplemental oral iron and folic acid since early pregnancy at the University of Benin Teaching Hospital was assessed later in pregnancy to test the efficacy of oral iron and folic acid in preventing iron deficiency and/or megaloblastic anaemia in our community. Only those pregnant patients with haemoglobin genotype AA or AS took part in the study. Nobody was excluded except those with CC or SC. 96.77% (30 out of 31 patients) had iron deficiency with no stainable iron in the bone marrow. 35.4% (11 out of 31 patients) had megaloblastic changes in the bone marrow. 32.2% (10 out of 31 patients) had a combined iron deficiency and megaloblastic anaemia while only one out of 31 patients (3.23%) had megaloblastic anaemia without concurrent iron deficiency. 60.4% (20 out of 31 patients) had iron deficiency alone without concomitant megaloblastic changes in marrow. The bone marrow in all the patients were normal in other respects except with regards to iron-deficiency and/or megaloblastic status. The significance of this high incidence of iron-deficiency and/or megaloblastic anaemia in patients already on routine pre-natal drugs is discussed. PMID- 4037417 TI - Serum copper in myocardial infarction--diagnostic and prognostic significance. AB - Serum copper estimations were carried out in 44 cases of acute myocardial infarction, 23 cases of angina and 40 age and sex matched healthy controls. A highly significant degree of rise in serum copper levels was observed in patients with acute myocardial infarction as compared to cases of angina and controls. The levels showed a gradual rise with peak on 7th day followed by a gradual decline returning to normal on 28th day. The pattern was the same both in complicated and uncomplicated cases except that values were still higher on the 28th day in complicated cases of acute myocardial infarction. Mean peak serum copper levels were significantly higher (p less than .001) in complicated cases of acute myocardial infarction as compared to uncomplicated cases. Significant correlation was found between serial serum copper changes and creatinine phosphokinase and lactic dehydrogenase levels. The prognostic and diagnostic significance of serum copper has been discussed. PMID- 4037418 TI - Pulse wave reflections at the aorto-iliac junction. AB - For pressure pulses to be transmitted to vital organ vascular beds, minimum loss through vascular branching junctions is necessary. Experimental measurements of pulse wave velocities and cross-sectional areas allowed branching reflections to be quantified. Wave reflections at normal aorto-iliac junction is minimal. Increased reflection occurs when the branch vessel is either narrowed or occluded. Also, geometric factors dominate over elastic factors in determining the amount of pulse wave reflections at the aorto-iliac junction. PMID- 4037419 TI - Viscerally induced cutaneous vasospasm. AB - Superficial vasomotor tone in the forearm has been thought to be dependent mostly on vasodilatation rather than vasoconstriction. Despite this view we report now that a mechanism for profound vasoconstriction exists in the forearm surface. This phenomenon was observed in normal subjects undergoing elective radial artery catheterization and the stimulus for the vasoconstriction consisted of the intra arterial infusion of normal saline (rate of 0.5 - 6.0 ml/min). Two components to this reaction were observed. A stable pericatheter zone of pallor varied in extent proportional to the rate of infusion. The second component consisted of distal patches of vasoconstriction over the whole anterior forearm surface which first appeared 5 to 10 seconds after the infusion rate was increased. These satellite areas tended to coalesce with sustained infusion but they were unstable over time. Local changes in vascular intrinsic regulation can account for the pericatheter vasoconstriction but this does not readily explain the observed distal changes. The time latency, distribution and evolution of the distal vasoconstriction suggests the operation of an autonomic vasomotor reflex arc. PMID- 4037420 TI - A non-invasive index of leg arterial perfusion pressure during walking, derived from cutaneous toe temperature. AB - This article describes and evaluates a non-invasive technique for continuous monitoring of hemodynamic changes in the legs during walking. The method involves monitoring of cutaneous toe temperature. In six normal subjects we have shown that, during exercise under carefully controlled conditions, a unique steady state toe temperature exists for any given leg arterial perfusion pressure, when perfusion pressure is varied by means of an external occluding ankle cuff. Further, we have demonstrated a strong correlation between this external ankle cuff pressure and the time rate of changes of toe temperature during the test period following occlusion. Correlation coefficients, r1, were between -1 and 0.88 (mean -0.95; standard deviation +/- 0.03) for big toe and between -1 and 0.87 (mean -0.94; standard deviation +/- 0.03) for third toe. We conclude that during walking the time profile of toe temperature changes is a useful index of changes in leg perfusion pressure. Therefore, toe temperature may be used to study the dynamics of leg arterial circulation in atherosclerotic occlusive diseases. PMID- 4037421 TI - Instead of "plethysmography": "kenoseography" and "plesmonegraphy". AB - The recording of volume changes in health and disease has from old been designated as "Plethysmography". This was supposed to be a correct term for the recording (graphein) of an increase in volume (plethysmos). The present paper shows that the choice of this term was not felicitous, and suggests an alternative. The first "plethysmographic" recordings are ascribed to Glisson (1622) and Swammerdam (1737). Since Glisson and Swammerdam did, in fact, record the volume of muscle to be constant on contraction, their measurements should probably have been referred to as "isography". This, however, is merely a historical matter. Presently venous outflow measurement is a common procedure to establish the diagnosis of deep vein thrombosis. Venous outflow is determined by recording the decrease in volume of a limb which occurs after release of a congestion cuff. As this is quite the opposite of what is meant by "Plethysmography", another indication is needed for this examination. It appears that a suitable alternative can be taken from ancient Greek medical literature. PMID- 4037422 TI - Iliac artery aneurysm in Behcet's disease: a case report. AB - Today, Behcet's disease is known as a multisystem disorder. Eye lesions, mouth and genital aphthous lesions, and skin lesions are accepted as major lesions. The disease also attacks the locomotor system, central nervous system, gastrointestinal system and also arteries and veins. According to available data, some 30% of the patients have vascular lesions; mostly thrombosis of the veins. Arterial thromboses have been rarely reported; and only a few number of arterial aneurysms are noted. Here we present an iliac artery aneurysm in a case of Behcet's disease. PMID- 4037423 TI - Nailfold capillary microscopy in essential mixed cryoglobulinemia: a report of several cases. AB - Nailfold capillaries were examined in eight patients with essential mixed cryoglobulinemia. Two patients disclosed marked abnormality. These patients had no Raynaud phenomenon. Four patients with Raynaud phenomenon disclosed normal capillary patterns. Thus, microvascular pathology in essential mixed cryoglobulinemia is not related to Raynaud phenomenon. PMID- 4037424 TI - The swine histocompatibility system SLA: serological studies in the common Swiss and Danish swine breeds. AB - Alloantisera were produced in common Swiss and Danish swine breeds by immunization with leucocytes or skin-grafts. Out of the 126 antisera, 66 were chosen for further study based on titrations employing lymphocytes from unrelated pigs typed with French SLA antisera (Vaiman, Chardon & Renard, 1979). The 66 selected antisera and the French reagents defining 26 SLA specificities were used to type lymphocytes from 595 unrelated pigs of the common Swiss and Danish breeds. The reaction-patterns of the French, Swiss and Danish antisera were adequately correlated for the French SLA specificities Nos FJ 2, 3, 6, 7, 8, 9, 11, 14, 19, 20 and 24 and for the haplotypes FJ 15.1.18 and FJ 5.4. In addition, a cluster of correlated Danish and Swiss antisera characterized a new specificity, provisionally designated CPH 31. This specificity was frequent in the Danish Landrace pigs. Using the reagents identified in this report, the segregation of SLA markers was studied. Back-cross families demonstrated segregation of 15 distinct SLA haplotypes of which 14 are common in French Landrace or Large White. Differences were found in haplotype frequencies in both the Swiss and the Danish Landrace and Large White breeds. PMID- 4037425 TI - Preliminary evidence of segregation distortion in the SLA system. AB - The segregation of 11 well-defined SLA haplotypes was investigated in 40 Land race and 48 Large White Danish and Swiss litters. Among the 11 haplotypes, the segregation of one (SLA 20-8.2.11) deviated significantly from the expected 1:1 segregation ratio in back-cross families. Tests indicated that these families were homogeneous with respect to segregation distortion, although the distortion was more pronounced in litters sired by heterozygous Danish boars than by heterozygous Swiss boars and Danish and Swiss sows. The data presented do not allow any definite conclusion about the cause of the segregation distortion. The possibility of the distortion being caused either by a complex similar to the T/t complex found in mouse and contemplated in man or directly by the SLA region is discussed. PMID- 4037426 TI - A comparison of bovine lymphocyte antigens. AB - In Canberra, 31 antigens have been described on the surface of bovine lymphocytes. Seven antigens are subgroups of other antigens. Eleven antigens are similar to the eleven antigens which have been described in Melbourne. Fourteen antigens are similar to twelve international-workshop antigens and two European workshop antigens. PMID- 4037427 TI - Expansion of the P blood group system of the horse. PMID- 4037428 TI - Studies on the bovine lymphocyte antigens and the production of lymphocytotoxic antibodies by parous cattle. AB - Studies were carried out to determine the time of appearance, frequency, titre and specificity of lymphocytotoxic antibodies in the plasma of parous Hereford cattle. Cytotoxic antibody was first detected in a small proportion (3/62 = 4.8%) of primigravid cattle during the last third of pregnancy. Titres were low (neat or 1 in 2) at this time and decreased in one animal so that antibodies were not detectable in samples obtained on the day of calving or 9 days beforehand. Following parturition, the proportion of primiparous cattle producing lymphocytotoxic antibodies increased markedly and reached a maximum value (8/19 = 42.1%) during the third month post partum. Antibody levels also rose over the same period. An increase in the parity of the dam also resulted in an increase in the proportion of cattle with lymphocytotoxic plasma. These antibodies appeared earlier in pregnancy, were at a higher titre and had a wider specificity than those found in primigravida. Non-foetally stimulated antibody was detected in 4 cattle. In one plasma sample, lymphocytotoxic activity was present prior to mating, and in the 3 others it was not directed against cells from either the bull to which the dam was mated or the calf produced by the sire and dam. PMID- 4037430 TI - Dust mite avoidance in the treatment of asthma. PMID- 4037429 TI - Blood group and protein polymorphism gene frequencies for seven breeds of horses in the United States. AB - Gene frequencies at 20 blood group and protein polymorphism loci (A, C, D, K, P, Q, U, Al, Tf, Pi, Xk, Es, Gc, PGD, CA, Cat, PGM, AP, Hb and PHI) are given for seven horse breeds in the United States (Thoroughbred, Arabian, Standardbred, Morgan, Quarter Horse, Paso Fino and Peruvian Paso). These data are used to calculate that the battery of tests is at least 96% effective for recognizing incorrect paternity in these breeds. In addition to paternity testing, these tests can be applied to studies of breed relationships. PMID- 4037431 TI - Use of Seralyzer system for theophylline level determination in an office setting. AB - Theophylline levels were measured on 63 plasma samples by both high pressure liquid chromatography and Seralyzer methods with excellent correlation. Seralyzer results were obtained quickly and easily in an office setting and offered the additional advantage of allowing accurate measurements on finger-stick samples. PMID- 4037432 TI - IgG is not the only inhibitor of IgE in the RAST test. AB - Blocking phenomenon of the RAST test was studied in the sera of 50 different patients. Specific levels of IgE and IgG against 11 common foods were evaluated by ELISA. Results showed that decreases in IgG levels by protein-A were not always followed by IgE increases. In this regard, we found three different combinations in the levels of IgE and IgG: (1) an IgG decrease followed by IgE increase (29%); (2) an IgG increase followed by IgE decrease (18%); and (3) both IgG and IgE decrease (28%). From these results we concluded that IgG is not the only inhibitor of the RAST test. PMID- 4037433 TI - The significance of the spores of the Basidiomycetes (mushrooms and their allies) in bronchial asthma and allergic rhinitis. AB - The role of Basidiospores in the allergic diathesis is poorly understood. Dialyzed extracts of Agaricus campestris, Coprinus micaceus, Fuligo septica, Lycoperdon perlatum, Scleroderma lycoperdoides, Ustilago maydis, and sooty mold were prepared from fresh spores. The study group consisted of 100 patients with asthma and 100 patients with allergic rhinitis. These 200 patients had symptoms occurring during October and November. All were intradermally skin tested with the seven extracts at concentrations of 1 microgram/mL or 10 micrograms/mL. No scratch or pressure puncture tests were performed. Skin tests were recorded at 15 minutes (pos = 5-mm wheal with 10-mm erythema or greater) and at six or 24 hours (pos = 6 mm or greater of induration and erythema). A total of 436 immediate reactions were observed in the asthmatic group (4.4/patient) compared with 129 in the rhinitic group (1.3/patient). The late phase reactions were just the opposite. The asthmatic group had 66 late phase reactions or 0.7/patient compared with 382 or 3.8/patient in the rhinitic group. This study demonstrates that patients with bronchial asthma have a higher incidence of immediate skin sensitivity by intradermal testing, whereas patients with allergic rhinitis have late phase sensitivity to these fungal spores. This study was performed in the eastern United States only; therefore, the clinical significance of the results will become more apparent once this study is repeated in other parts of the country by other investigators. PMID- 4037434 TI - Therapy of acute asthma: I. Evaluation of successive bronchodilator treatments. AB - Ninety-one children with acute asthma were studied to determine the extent of incremental improvement in pulmonary function afforded by successive doses of subcutaneous epinephrine, and by a bronchodilator aerosol in those patients refractory to epinephrine. A significant proportion of patients (69%), as expected, responded to the first injection. Among those who did not respond to the first injection a significant proportion (30%) responded to the second injection. Markedly fewer patients responded to subsequent bronchodilator treatments, including aerosols, if they did not improve significantly after the first two treatments. Patients with higher initial peak flow rates (PEFR) generally required fewer epinephrine injections, and achieved higher maximal PEFR than those with lower initial PEFR. Most asthmatic patients who required hospital admission had lower initial peak flow rates, were less responsive to epinephrine injections, and achieved lower maximal rates than those who could be discharged home. PMID- 4037435 TI - Tropical island asthma in Hawaii. AB - To better understand the increased morbidity and mortality of asthma in Hawaii, a profile was established from questionnaires completed by 76 asthmatics in a residential area and by 204 asthmatics attending emergency rooms. The general profile differed from profiles on other islands and mainland USA in that allergens were more important and exercise less. Variations occurred in the profile in association with ethnicity, time in Hawaii, and prescribing habits. The Chinese did not recognize infection as a trigger; the Filipinos had little familial asthma, less pollen sensitivity, and used few steroids; and the Japanese were sensitive to Kona weather but not to pollen. The newcomers (military) who were sensitive to pollen and less to emotion and exercise, rated their attacks more severe and used more nebulizers and steroids. Certain other relationships emerged such as house dust as a trigger and the increased use of steroids. Asthmatics of two civilian ERs used fewer nebulizers and steroids. In conclusion, Hawaii's increased morbidity and mortality of asthma should be examined further in terms of ethnicity, infection, house dust, and prescribing habits. PMID- 4037436 TI - House dust control and asthma: a placebo-control trial of cleaning air filtration. AB - Using a placebo-control single-blind crossover trial, we investigated the effects of dust control measures alone and combined with electrostatic and high efficiency particulate air filters in the bedrooms of patients with asthma. Of 12 young asthmatics allergic to house dust and dust mite who entered the trial, nine completed all four 2-week intervals. No statistically significant improvement in symptom scores or peak expiratory flow above that recorded during the placebo interval occurred during any treatment phase. We conclude that house dust suppression adds little to the management of otherwise well controlled young asthmatic patients. PMID- 4037437 TI - Associated cutaneous findings in nickel contact sensitivity. AB - A clinical survey of patients with nickel dermatitis has provided evidence of a significant association with one or more of the following reactions: contact reaction from adhesive tape, reaction from mosquito bites which lasts 1 week or longer, and a history of hives. The association of nickel contact dermatitis with at least one of the other reactions is termed contact sensitivity syndrome. PMID- 4037438 TI - Prevalence of occupational asthma in silk filatures. AB - A clinical survey in two silk filatures revealed that 36.2% of the persons engaged in the processing of natural silk were suffering from bronchial asthma, while 16.9% of the total subjects had asthma of occupational origin. Skin prick tests using crude silkworm cocoon and pupal allergen extracts revealed that 28.8% of the subjects were sensitive to the silkworm-derived allergens. IgE antibodies specific to both cocoon and pupal allergens were demonstrable by RAST in the sera of patients with positive skin reactions and occupational asthma. PMID- 4037439 TI - Measurement of serum IgE concentrations in cancer patients. PMID- 4037440 TI - [Is automatic oscillometric measurement of blood pressure reliable in hypotension?]. AB - The reliability of an automatic oscillometric device for measurement of blood pressure (BP) was assessed in a large range of BP values during intraoperative normotension and induced hypotension. Direct BP measurements were carried out with a radial catheter. Data were compared with those obtained with the oscillometric device placed on the opposite arm. Nine patients were studied, undergoing 234 measurements of BP ranging from 55 to 208 mmHg (7.3 to 27.7 kPa) for systolic blood pressure (Pasys), from 32 to 130 mmHg (4.3 to 17.3 kPa) for diastolic blood pressure (Padia) and from 36 to 154 mmHg (4.8 to 20.5 kPa) for mean blood pressure (Pa). Good correlation between the two techniques was found for Pasys measurements recorded during both normotension and hypotension (r = 0.93; p less than 0.01). 92% of the values recorded with the oscillometric device were lower than those measured invasively. In the other cases (8% of the data), the mean difference between the two techniques was 5.5 mmHg (0.7 kPa). When BP values lower than 90 mmHg (12 kPa) for Pasys, 60 mmHg (8 kPa) for Padia and 70 mmHg (9,3 kPa) for Pa were considered individually, the correlation coefficients were 0.83, 0.73 and 0.77 respectively. These findings suggested that the oscillometric method can be considered as relatively suitable for monitoring moderate hypotension induced by vasodilators. The invasive technique must however remain the method of choice during profound hypotension. PMID- 4037441 TI - [Peridural morphine in intractable cancer pains. Means and obstacles]. AB - Long-term analgesia with epidural morphine (EM) is a new tool in the management of intractable cancer pain. Twenty-six out of 160 cancer patients referred to the Pain Division for pain assessment were selected for analgesia with long-term epidural morphine, so aiming to define its place amongst more traditional methods of treatment, such as drugs, nerve-blocks, neurosurgery or radiotherapy. All 26 patients were cases of conventional analgesic failure, with very advanced cancer states. Thirteen patients became absolutely pain free throughout the treatment period: five of them were even allowed home. Another ten patients were satisfied with EM, though some residual pain of neurogenic and visceral type persisted. In three patients, epidural morphine was judged as a complete failure. The 134 other patients could be managed with either of the other above mentioned techniques. The most important selection criterion for patients requiring epidural morphine seemed to be continuous multiple site bilateral pain of deep somatic origin. The response was variable in continuous visceral pain, while neurogenic, cutaneous and intermittent pain due to intestinal obstruction responded only exceptionally. EM was most valuable in terminal situations when systemic opiates failed to give satisfactory analgesia, or in acute transitory situations, while waiting for a response to cancer-orientated therapy. Epidural morphine considerably improved the patients' quality of life, compared with conventional methods tried beforehand. Analgesic methods in cancer are palliative procedures. In terminal or temporary situations, other more invasive methods are not suited. The EM technique is simple, adjustable to advancing pain and has few side-effects, especially when compared with neurolytic and neurosurgical procedures. PMID- 4037442 TI - [Inhibition of postoperative muscular proteolysis by sodium alpha ketoisocaproate: does a dose-effect relation exist?]. AB - The inhibitory effect of branched chain amino acids on muscle protein breakdown has been attributed to the ketoanalogue of leucine, alpha-ketoisocaproic acid. In an attempt to demonstrate a possible dose-response relationship for ketoleucine, the postoperative protein breakdown (using urinary excretion of 3 methylhistidine, creatinine and nitrogen) was evaluated in 29 patients undergoing gynaecological surgery. They were randomly assigned to one of the following groups: group A (ten patients) received 3 g of glucose per kilo and per day, group B (ten patients) received glucose + 100 mg X kg-1 X d-1 of ketoleucine and group C (nine patients) glucose + 200 mg X kg-1 X d-1 of ketoleucine. The study was performed over a period of 72 h. The 3-methylhistidine/creatinine ratio was significantly lower in groups B and C than in group A (respectively 28.47, 28.07 and 32.08). These results confirmed the inhibitory effect of ketoleucine on muscle protein breakdown. However there was no difference between group B and group C. In conclusion, this study did not demonstrate a dose-response relationship for ketoleucine in moderate postoperative catabolism. PMID- 4037443 TI - [Changes in temperature during transurethral resection of the prostate under peridural anesthesia]. AB - Superficial and central body temperatures were measured during anaesthesia and recovery in eleven elderly patients undergoing transurethral resection under epidural anaesthesia. A significant decrease in central body temperature as measured on the tympanic membrane was found during surgery. After a significant increase during induction of anaesthesia, mean skin temperature remained stable throughout surgery. Mean body temperature calculated from central body temperature and mean skin temperature decreased significantly during surgery. During recovery, all temperatures increased significantly. But mean body temperature returned to normal faster than central body temperature. Routine monitoring of core temperature and the use of warmed irrigation fluids are recommended during transurethral resections in elderly patients. PMID- 4037444 TI - [Anesthesia with controlled hypotension for treatment of intracranial arterial aneurysm in an infant]. AB - A case is reported of a ruptured intracranial aneurysm of the posterior cerebral artery in a 21/2 month old infant. The clinical picture of subarachnoid haemorrhage included coma, seizures and left hemiparesis. The aneurysm was detected by two dimensional ultrasonography and CT scan. The carotid and vertebral arteriogram showed an aneurysm located on the posterior cerebral artery. Surgery was performed after neurological improvement, 25 days after admission. The operation was conducted under controlled systemic hypotension using sodium nitroprusside. The mean blood pressure was decreased from 70 mmHg to 40 mmHg during 20 min. This technique established good haemostatic conditions during removal of the aneurysm. Postoperative recovery was uneventful with full neurological recovery. The interest of sodium nitroprusside as a hypotensive agent is discussed. The difficulties of monitoring haemodynamic variables in infants are stressed. PMID- 4037445 TI - [Apparently severe arterial hypertension: limitations of sphygmomanometry]. AB - Monckeberg's sclerosis is characterized by medial arterial calcifications. This disease usually occurs in old people and the lesions are observed in distal lower limb arteries. The evolution is generally asymptomatic. The other arteries are uncommonly affected. This report concerns a patient with exceptionally extensive disease and simultaneous asymptomatic arterial hypertension. Blood pressure measured non invasively represents the force required to compress the brachial artery, and not the real blood pressure. In such patients, blood pressure should be monitored during anaesthesia through arterial cannulation. PMID- 4037446 TI - [Fatal poisoning by alcohol-free aniseed aperitif]. AB - A case of chronic poisoning with alcohol-free "pastis" leading to the death of a 32 year old alcoholic patient is reported. The mean daily amount of ingested glycyrrhizinic acid was 0.35 g. "Torsades de pointes" secondary to severe hypokalemia were observed and prolonged cardiac arrest occurred. There was evidence of chronic hypokalemic myopathy and of rhabdomyolysis with acute renal failure. Furthermore, the origin of an associated cardiomyopathy is discussed. PMID- 4037447 TI - [Congenital factor XII deficiency: a rare cause of increased activated cephalin time]. AB - The fortuitous detection of an increased activated cephalin clotting time is often dependent on defects of the blood-clotting factors synthesized by the liver, haemophilia or von Willebrand's disease, circulating anticoagulants or specific deficiencies of various factors necessary for blood-clotting mechanisms. Much more rarely, it may be due to an isolated Hageman factor defect. This deficiency does not lead to an increased bleeding tendency and surgery has proved surprisingly uneventful. On the other hand, thromboembolic events may appear. Being and inherited disease with autosomal recessive transmission, the discovery of Hageman factor deficiency must lead to a complete family investigation. PMID- 4037448 TI - [Serum assay of lidocaine after intrabronchial administration]. PMID- 4037449 TI - [Postoperative changes in plasma fibronectin. Influence of the type of anesthesia]. PMID- 4037450 TI - [Pulsed-gas ventilation]. PMID- 4037451 TI - [Postoperative analgesia by the continuous peridural administration of ketamine]. PMID- 4037452 TI - [Cardiogenic shock]. PMID- 4037453 TI - Biological control systems. Selected papers from the Biomedical Society 1984 Symposium. April 2-5, St. Louis, Missouri. PMID- 4037454 TI - Automatic control of blood pressures with multiple drug inputs. AB - Control of arterial blood pressure has been successfully achieved by infusing a single vasoactive drug. However, in clinical practice, blood pressures are frequently controlled using multiple drug infusions. This paper presents a computer based adaptive control algorithm for simultaneous infusions of both an inotropic agent and a vasoactive agent to maintain the blood pressures at desired levels. We present the dynamics of the system with a bilinear two-input, two output model. A least-squares parameter estimation algorithm has been employed using an output error method. Results of computer simulations of an electrical analog model of the heart and circulatory system are presented. PMID- 4037455 TI - Renal cortical perfusion--preliminary experience with the dynamic spatial reconstructor (DSR). AB - The three-dimensional image data generated by the Dynamic Spatial Reconstructor (DSR) enables measurement of the three-dimensional distribution of blood supply in organs. We have applied this imaging technique to evaluate renal cortical blood flow distribution and compare it with distribution of radiolabeled microspheres. The DSR, a high temporal resolution volumetric roentgenographic computed tomographic scanner, was used to scan the volume containing a kidney in 0.13-0.26 s and repeating this scan 8-4 times per s for six s during a renal arteriogram. Five anesthetized dogs were studied in the prone position with the left kidney exteriorized through a flank incision. An electromagnetic flowmeter was placed around the renal artery and a needle placed retrograde into the artery for injection of a 2 cc bolus of contrast agent. During the scan the contrast agent was injected over a four s period during which radioactively labelled microspheres were injected into the left atrium. The tomographic images of approximately 10 parallel, 5 mm thick sagittal slices corresponding to the slices of the kidney used for counting microspheres in the cortical layers were displayed and analyzed. The time point chosen for analysis was the one in which peak brightness (i.e., concentration of contrast agent) was detected in the cortex. The spatial distribution of peak brightness values was compared to the number of microspheres at the same sampling locations. The microsphere-based value of regional cortical blood flow fell below the regression line for the juxtamedullary cortex and above for the outer cortex. This result is consistent with the preferential distribution of microspheres to the outer cortex whereas the contrast agent distributed more uniformly throughout the cortex. PMID- 4037456 TI - Videomicroscopic method for direct determination of blood flow to the papilla of the kidney. AB - We adapted the technique of videomicroscopy for direct determination of blood flow in individual capillaries of the papilla of the kidney, the ascending vasa recta (AVR) and descending vasa recta (DVR). The papilla was exposed in anesthetized rats and positioned under a video-camera-microscope and viewed under epiillumination. The intravenous infusion of fluorescein-isothiocyanate (FITC) labeled gamma globulin was combined with fluorescence microscopy to enhance the contrast among plasma, red blood cells and capillary walls. On the television monitor, the walls were clearly outlined, enabling the measurement of capillary diameter. The velocity of red cells (Vrbc) in individual vasa recta was measured using the dual slit technique. From the videotape recorded microscopic image of a vas rectum, two photometric signals were obtained by integrating the light intensity from two electronic "windows" positioned closely together over the same capillary. Red cell velocity was calculated by dividing the distance between the two windows by the time delay between signals. The delay was determined using analog correlation tracking or digital cross correlation techniques. Single vasa recta blood flow was calculated from capillary diameter, Vrbc, and F (Fahraeus factor), which converts Vrbc to average whole blood velocity, Vblood. In quartz capillaries the same size as vasa recta, the ratio F = Vrbc/Vblood = 1.42 +/- 0.06. Total papillary blood inflow and outflow was calculated by multiplying the total number of DVR or AVR times the mean single capillary blood flow for DVR or AVR, respectively. PMID- 4037457 TI - Myogenic tone and cerebral vascular autoregulation: the role of a stretch dependent mechanism. PMID- 4037458 TI - Influence of transmural pressure of myogenic responses of isolated cerebral arteries of the rat. AB - We examined the diameter responses of isolated and pressurized posterior cerebral artery branches to various static and dynamic pressure alterations. These vessels, dissected from an anatomically identifiable location in the rat brain, developed tone when placed in a normal calcium physiological salt solution (1.6 mM Ca-PSS). Following a series of transmural pressure steps (delta p) of 25 or 50 mm Hg completed in 1-2 s and made every 5 min, they attained additional tone resulting in a mean luminal diameter of 139 micron at 100 mm Hg which was 35% less than their relaxed size measured in 1 mM EGTA-PSS. Continuous measurements of wall thickness and lumen diameter were obtained using a video electronic system in 1-2 mm long arterial segments, and autoregulatory gain factors calculated. Myogenic responses were obtained from each of 6 vessels taken from 6 WKY rats. Diameters following the step pressure changes were usually stable within 2-4 min. The data defined a myogenic regulatory pressure range from 49-145 mm Hg. Gain values averaged about 17% of that necessary for these arteries to maintain perfect flow autoregulation. Our results for myogenicity are comparable with the pressure range for blood flow autoregulation reported by others for the rat. We conclude that myogenic mechanisms, at least in this size artery, are partly responsible for flow autoregulation, and that they are supplemented by metabolic mechanisms operative in the intact rat brain. PMID- 4037459 TI - Vasopressin induced rhythmic activity in rat basilar artery. AB - The effects of vasopressin on membrane potential and tension were studied in isolated segments of basilar arteries from the University of Iowa colonies of normotensive inbred Kyoto-Wistar rats (WKY) and stroke-prone spontaneously hypertensive rats (SP-SHR). In the presence of vasopressin (0.01-0.3 IU/ml), basilar arteries from WKY, but not from SP-SHR, developed rhythmic contractions. These contractions were recorded in 13 of 14 WKY basilar arteries, were unaffected by pretreatment with 6-hydroxydopamine, and were characterized by 20 100 dyne oscillations in tension, occurring 1-3 cycles/min, and superimposed on the vasopressin-induced contraction (averaging 60 dynes at 0.01 IU/ml or 160 dynes at 0.3 IU/ml). However, resting membrane potentials were not different in SP-SHR vs. WKY at 37 degrees C, and both strains showed about the same (11 mV) depolarization by 0.1 IU/ml of vasopressin. The rhythmic contractions were enhanced by K+-free solution, and abolished in the presence of high K+ solution (30 mM), suggesting that active Na+-K+ transport may be involved in modulating the rhythmic activity. These findings are consistent with the hypothesis that the vasopressin-induced rhythmic contractions in WKY basilar arteries are at least partly dependent on a reduced activity of electrogenic Na+-K+ active transport in WKY as compared to SP-SHR. PMID- 4037460 TI - Cerebrovascular transmural pressure and autoregulation. AB - The cerebral blood flow (CBF) response to changes in perfusion pressure mediated through decreases in arterial pressure, increases in cerebrospinal fluid (CSF) pressure and increases in jugular venous pressure was studied in anesthetized dogs. A preparation was developed in which each of the three relevant pressures could be controlled and manipulated independently of each other. In this preparation, the superior vena cava and femoral vein were cannulated and drained into a reservoir. Blood was pumped from the reservoir into the right atrium. With this system, mean arterial pressure and jugular venous pressure could be independently controlled. CSF pressure (measured in the lateral ventricle) could be manipulated via a cisternal puncture. Total and regional CBF responses to alterations in perfusion pressure were studied with the radiolabelled microsphere technique. Each hemisphere was sectioned into 13 regions: spinal cord, cerebellum, medulla, pons, midbrain, diencephalon, caudate, hippocampus, parahippocampal gyrus, and occipital, temporal, parietal and frontal lobes. Despite 30 mm Hg reductions in arterial pressure or increases in jugular venous pressure or CSF pressure, little change in CBF was observed provided the perfusion pressure (arterial pressure minus jugular venous pressure or CSF pressure depending on which pressure was of greater magnitude) was greater than the lower limit for cerebral autoregulation (approximately 60 mm Hg). However, when the perfusion pressure was reduced by any of the three different methods to levels less than 60 mm Hg (average of 48 mm Hg), a comparable reduction (25-35%) in both total and regional CBF was obtained. Thus comparable changes in the perfusion pressure gradient established by decreasing arterial pressure, increasing jugular venous pressure and increasing CSF pressure resulted in similar total and regional blood flow responses. Independent alterations of arterial and CSF pressures, and jugular venous pressure produce opposite changes in vascular transmural pressure yet result in similar CBF responses. These results show that cerebral autoregulation is a function of the perfusion pressure gradient and cannot be accounted for predominantly by myogenic mechanisms. PMID- 4037461 TI - The role of adenosine in autoregulation of cerebral blood flow. AB - We have investigated the role of adenosine, a purine nucleoside and potent vasodilator of cerebral pial vessels, during both acute (0-60 sec) and sustained (2-5 min) changes in cerebral perfusion pressure. Brain adenosine concentrations are rapidly increased within 5 sec of the onset of systemic hypotension and parallel, in a temporal fashion, the changes in pial vessel diameter and alterations in cerebral vascular resistance. During sustained hypotension, brain levels of adenosine are increased even within the autoregulatory range. These data are constant with the hypothesis that adenosine is an important metabolic factor in cerebral autoregulation. PMID- 4037462 TI - Oxygen-dependent mechanisms in cerebral autoregulation. AB - Autoregulatory adjustments in the caliber of cerebral arterioles were studied in anesthetized cats equipped with cranial windows for the direct observation of the pial microcirculation. Increased venous pressure caused slight, but consistent, arteriolar dilation, at normal and at reduced arterial blood pressure and irrespective of whether or not intracranial pressure was kept constant or allowed to increase. Arterial hypotension caused arteriolar dilation which was inhibited partially by perfusion of the space under the cranial window with artificial CSF equilibrated with high concentrations of oxygen. This vasodilation was inhibited to a greater extent by perfusion of the space under the cranial window with fluorocarbon FC-80, equilibrated with high concentrations of oxygen. CSF or fluorocarbon equilibrated with nitrogen did not influence the vasodilation in response to arterial hypotension. The response to increased venous pressure was converted to vasoconstriction when fluorocarbon equilibrated with high concentrations of oxygen was flowing under the cranial window. The vasodilation in response to arterial hypotension was inhibited by topical application of adenosine deaminase. The results show that both metabolic and myogenic mechanisms play a role in cerebral arteriolar autoregulation. Under normal conditions, the metabolic mechanisms predominate. The presence of the myogenic mechanisms may be unmasked by preventing the operation of the metabolic mechanisms. The major metabolic mechanism seems to be dependent on changes in PO2 within the brain with secondary release of adenosine. PMID- 4037463 TI - A cellular mechanism for myogenic regulation of cat cerebral arteries. AB - Autoregulation of cerebral blood flow is accomplished through integration of metabolic, neurogenic and myogenic mechanisms. Myogenic mechanisms involve activation of cerebral arterial muscle cells as transmural pressure increases, providing a means through which vessel caliber can be regulated to maintain blood flow constant. The cellular mechanisms involved in this myogenic response may involve changes in the electrical potential across the plasma membrane. When isolated cat middle cerebral arteries are cannulated and prepared in a manner allowing manipulation of transmural pressure, the muscle cell membrane depolarizes as pressure increases. The degree of membrane depolarization in response to an elevated pressure is dependent upon extracellular Ca2+ [( Ca]o), increasing as [Ca]o is elevated and markedly decreasing as [Ca]o is reduced to low levels. When these arterial preparations are maintained at a physiological pressure of around 100 mm Hg, spontaneous action potentials can be recorded which increase in frequency upon further elevation in pressure. Vessels exhibiting such electrical activity can be observed to decrease in diameter as pressure is increased. Such finding suggest a membrane electrical mechanism for myogenic autoregulation of cerebral arteries. PMID- 4037464 TI - Yohimbine: a new street drug. AB - Following the ingestion of an alleged aphrodisiac known as "yo-yo," a 16-year-old girl experienced an acute dissociative reaction accompanied by weakness, paresthesias, and incoordination. Subsequent symptoms included anxiety, headache, nausea, palpitations, and chest pain. Hypertension, tachycardia, tachypnea, diaphoresis, pallor, tremors, and an erythematous rash were noted on physical examination. Serum epinephrine and norepinephrine levels were found to be elevated. Symptoms resolved spontaneously but lasted approximately 36 hours. The ingested substance was identified as yohimbine. The pharmacology of yohimbine and the treatment of yohimbine poisoning are discussed. PMID- 4037465 TI - Syncope and conduction disturbances following sublingual nifedipine for hypertension. AB - We present a case of a 79-year-old woman with periods of syncope, complete heart block (CHB), and ventricular standstill during periods of increased vagal tone following sublingual nifedipine for hypertension. The syncopal episodes were associated with periods of elevated vagal tone (micturition and vomiting) with one monitored episode showing a clear time course of emesis; CHB then ensued, progressing to ventricular standstill with loss of consciousness that resolved over several minutes. Although nifedipine is not thought to affect conduction at current clinical dosages, it seems likely that the additive effects of nifedipine and elevated vagal tone produced the observed conduction abnormalities. This is the first case report of nifedipine administration followed by syncope and conduction disturbances. PMID- 4037466 TI - Neurotoxicity of meperidine. AB - Meperidine neurotoxicity manifests as shakiness, tremors, myoclonus, and seizures. It is generally seen with repeated parenteral use. We report a case of meperidine neurotoxicity from oral use by an otherwise healthy woman. The pharmacology and clinical implications are discussed. PMID- 4037467 TI - An unusual presentation of spontaneous pneumomediastinum. AB - Spontaneous pneumomediastinum is an uncommon disease that often presents with subtle clinical and radiographic findings. During a two-week period, three patients presented with complaints of throat and neck pain. The first complained of difficulty swallowing and throat and chest discomfort; accurate diagnosis was delayed because of the unusual presenting symptoms. The second had severe throat pain. The third presented with unstable vital signs, throat and neck pain, and air in the pericardium and mediastinum. Review of the first case facilitated the correct diagnosis of spontaneous pneumomediastinum in the subsequent cases. All three patients were discharged free of symptoms. PMID- 4037468 TI - Calcific tendonitis of the longus colli muscle: a cause of atraumatic neck pain. AB - Retropharyngeal calcific tendonitis is a not-infrequent cause of atraumatic neck pain. Two patients presented with neck pain and stiffness, one with associated dysphagia. Cervical spine radiographs showed calcification anterior to the dens, establishing the diagnosis of calcific tendonitis of the longus colli muscle. Treatment with analgesics and antiinflammatory agents brought relief of symptoms within one week. A review of the literature shows that these patients had courses similar to those in previously reported cases. PMID- 4037469 TI - Disaster medical services. American College of Emergency Physicians. PMID- 4037470 TI - Moulage in a disaster simulation exercise. PMID- 4037471 TI - Use of a surgical glove when repairing finger injuries. PMID- 4037472 TI - Hypothermia therapy. PMID- 4037473 TI - Effect of timolol on the sympathetic nervous system in coronary occlusion in cats. AB - Clinical studies have shown that treatment with chronic timolol after a myocardial infarction decreases the incidence of reinfarction and mortality. It also limits the size of infarction when it is given IV during the acute phase of an infarction and followed by chronic oral dosing. It has been postulated that beta blockers work not only by a direct mechanism on the heart, but by altering neural discharge to the heart and depressing the sympathetic overactivity seen in 35% of patients immediately after an infarction. Our study examined the effect of timolol on sympathetic cardiac neural discharge, blood pressure, heart rate, and rhythm during acute coronary occlusion produced by ligation of the left anterior descending artery 10 to 14 mm below its origin in alpha-chloralose-anesthetized cats. Timolol or normal saline 5 mg/kg IV was given five minutes post coronary occlusion. The infusion of timolol significantly decreased the mean arterial blood pressure and heart rate. Sympathetic cardiac neural discharge in the group treated with timolol five minutes post coronary occlusion did not differ from that in the saline group. Thus there was a nonuniform (an increase, a decrease, or no change) sympathetic cardiac neural discharge associated with the production of occlusion-induced arrhythmia. These data suggest that the action of timolol on the sympathetic cardiac neural discharge is not its major mode of protection. PMID- 4037474 TI - The influence of verapamil on dopamine's ability to augment cardiac output. AB - Calcium channel blockers are used in the treatment of angina pectoris, cardiac arrhythmia, and hypertension. Sporadic reports of hypotensive reactions to verapamil have indicated that these reactions are not reversed readily by catecholamine administration. This study was conducted to test the hypothesis that verapamil pretreatment does not alter the ability of dopamine in conventional doses to augment cardiac output. Twelve mongrel dogs, weighing 19 to 25 kg, were anesthetized with pentobarbital and placed on a respirator. Heart rate, cardiac output, and the right atrial, pulmonary artery, pulmonary capillary wedge, and central aortic pressures were measured directly. Dopamine, 10 micrograms/kg/min, increased cardiac index by 52.4 mL/kg/min over baseline. The dopamine was stopped and the animals were allowed to return to baseline. Dopamine, 10 micrograms/kg/min, was administered again after pretreatment with 0.15 mg/kg verapamil, and it increased cardiac index by 47.9 mL/kg/min over the second baseline control. The results were not statistically different using the Student t test for paired data (P greater than .05). It is concluded that verapamil does not affect dopamine's ability to augment cardiac output in the dosages tested. PMID- 4037475 TI - Should the emergency IVP be used more selectively in blunt renal trauma? AB - A retrospective study was performed to determine if the emergency intravenous pyelogram (IVP) is being overused in the evaluation of blunt renal trauma. Medical records of 105 blunt renal trauma patients undergoing IVPs for suspected blunt renal trauma were analyzed. Eighty-eight patients (83.8%) had normal IVPs, and 17 patients (16.2%) had abnormal IVPs. Three of the 105 patients (2.9%) required urologic surgical intervention. The medical records of these patients were examined in detail because it was believed that this patient population needed to be identified by emergency IVP. All three patients requiring urologic surgery had gross hematuria. All three patients had one or more associated injuries. Two of the three patients had flank tenderness and/or flank mass. The third patient was obtunded. From this study and information from the literature an algorithm has been constructed as a guideline for a prospective study. Following this guideline no patients in the study requiring urologic surgical intervention would have been missed. Of patients requiring an emergency IVP, 7.3% would have required urologic surgery. This would have resulted in a savings of $10,432 at our institution. PMID- 4037476 TI - Effects of rapid infusion with high pressure and large-bore i.v. tubing on red blood cell lysis and warming. AB - A prototype large-bore intravenous tubing was developed and tested. Mean flow rates for blood (Hct 45%) and tap water were determined for several catheters at 600 mm Hg, 300 mm Hg, and gravity flow and were statistically analyzed by calculating the 95% confidence intervals. The degree of hemolysis during high pressure and flow was determined by measuring the plasma free hemoglobin using the spectrophotometric method. To determine if cold banked blood can be adequately warmed at high flow rates, thermocouples were used to measure the blood temperature before and after rapid infusion through a blood warmer. Results included maximum flow rates of 1,764 mL/min for tap water, and 1,714 mL/min for blood (Hct 45%) at 600 mm Hg through the large-bore tubing and an 8.5-F catheter. Flow rates for other pressure and catheter combinations were tabulated. The plasma-free hemoglobin increased slightly compared to controls with high pressure (less than or equal to 600 mm Hg) and flow rates. The increase correlated with less than 1% red blood cell lysis in all trials. When 13 C blood was infused through a warmer, blood temperature increased to 25.3 C at the maximum flow rate of 732 mL/min. Slightly higher heat gain resulted with slower infusion rates. We conclude that the prototype large-bore tubing and up to 600 mm Hg pressure provide rapid flow rates without significant hemolysis. Blood warming may be inadequate at higher flow rates. PMID- 4037477 TI - Emergency evaluation of cervical spine injuries: CT versus plain radiographs. AB - The recognition and appropriate initial management of the patient with an acute cervical spine injury in the ED is important because of the devastating and catastrophic effects of spinal cord injury. The use of computed tomography (CT) scan compared with initial plain radiographs in the detection of acute blunt traumatic cervical spine injury was evaluated in 20 patients. There was a disparity between the plain film and the CT scan as read by an attending radiologist in 12 patients (60%). In five patients (25%) the plain radiograph suggested a fracture or dislocation that was confirmed by CT scan. In eight patients (40%) the cervical spine film was read as a fracture, dislocation, or soft tissue widening between the cervical spine vertebrae. CT scan done later after admission was normal. In the remaining seven patients the plain film was read as "normal." CT scan, however, was normal in only three, and in four of these seven patients there was a discrepancy between the plain radiograph and the CT. Thus in four of 20 patients (20%) the plain film was read as "normal," while CT scan showed a fracture in our study. CT scan was superior to plain films in diagnosing cervical spine trauma, and it eliminated the false-positive (40%) and false-negative (20%) results obtained by relying on plain radiographs alone. PMID- 4037478 TI - The effect of telemetry on urban prehospital cardiac care. AB - A three-year, controlled trial of the use of telemetry in the prehospital care of cardiac patients was conducted in a major metropolitan area. Five of the ten paramedic squads in the city used telemetry; the other five squads did not. We studied the effect of telemetry on the following: paramedics' abilities to recognize ECGs in a written test; paramedics' abilities to identify ECG arrhythmias in the field; length of time spent by paramedics in the field; survival rates of patients with ventricular fibrillation (VF) cared for by paramedics; abilities of base station physicians to interpret telemetered ECGs; and attitudes of paramedics toward using telemetry. Telemetry was not found to affect the abilities of paramedics to read ECGs in either test or field situations. Paramedics who used telemetry spent more time in the field with their patients than did paramedics who did not use telemetry (P less than .02). We found no statistically significant effect of telemetry on survival rates of VF patients. Using matched ECGs, readings by base station physicians were found to be more accurate than were those by paramedics (P less than .01). Paramedics overwhelmingly reported that telemetry did not help them to save patients' lives, but that it did help them to treat patients with certain arrhythmias. The results suggest that telemetry may not improve either paramedics' abilities to identify arrhythmias or prehospital care for all cardiac patients. The implications for emergency services researchers are discussed. PMID- 4037479 TI - The ten-year malpractice experience of a large urban EMS system. AB - Malpractice is a recognized and growing problem for physicians and hospitals, but it is difficult to ascertain the risk of malpractice in the prehospital arena. Dade County, Florida (greater Miami), with a population of 1.7 million, currently is served by 339 certified paramedics. During the decade of 1972 to 1982, Dade County Fire Rescue handled 265,060 incidents; 16 claims were filed with the Risk Management Division of Dade County. The claims were produced by 11 incidents, which yields a rate of one per 24,096 incidents. The two greatest problems identified were inadequate record keeping and "gray zone" patients who do not fit any particular protocol. PMID- 4037480 TI - Methodology reporting in three acute care journals: replication and reliability. AB - As the sciences of emergency medicine and acute care medicine develop, it becomes imperative for researchers in these fields to accurately and completely report the methodology of their investigations. It is only through complete reporting that other investigators can critically examine, replicate, or expand on the results of an investigation. The purpose of our study was to compare the completeness of methodology reporting in three acute care journals, Annals of Emergency Medicine, Critical Care Medicine, and Journal of Trauma. Thirty-eight criteria characteristics necessary for the replication of a clinical trial were identified and grouped into ten categories. The categories were experimental design, recruitment and exclusion of subjects, selection of study sample, subject allocation, therapeutic regimen, blindness, outcome criteria, analysis of confounders, withdrawal of subjects, and statistical analysis. All prospective, interventional, controlled trials appearing in these journals from January 1980 to June 1983 were identified. A total of 45 trials were found. Each trial was read independently by two reviewers to determine whether each of the 38 criteria was clearly reported, not clearly reported, or not applicable. Disagreements were resolved by a third reader (adjudicator). The results are reported as the mean proportion of items clearly reported +/- standard deviation: Annals of Emergency Medicine (n = 16), 0.39 +/- 0.10; Journal of Trauma (n = 18), 0.33 +/- 0.14; and Critical Care Medicine (n = 11), 0.32 +/- 0.09. A one-way analysis of variance found no statistically significant difference between journals with respect to these proportions (P = .25).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4037481 TI - When less is more: Teflon and telemetry in the space age. PMID- 4037482 TI - Paramedic services--a true extension of emergency medicine. PMID- 4037483 TI - Emergency IVP in blunt renal trauma. PMID- 4037484 TI - Borderline personality disorder. PMID- 4037485 TI - Effect of diuresis on urinary excretion and creatinine clearance in the horse. AB - Endogenous creatinine clearance and renal excretion of phenylbutazone, osmotically active material, and compounds contributing to the urinary refractive index were studied in 12 Thoroughbred mares after no treatment, after water administration, or after furosemide administration. Urine was quantitatively collected, using urinary bladder catheters. On average, urine flow of the mares was 9 microliters/min/kg without treatment and increased to about 50 microliters/min/kg after water administration and to about 70 microliters/min/kg after furosemide administration. Water administration increased creatinine clearance values and excretion of phenylbutazone. Furosemide administration increased urinary excretion of osmotically active compounds and compounds contributing to urinary refractive index and decreased excretion of phenylbutazone. PMID- 4037486 TI - Pharmacokinetics of small doses of 3-methylindole given to horses. AB - The pharmacokinetics of 3-methylindole (3MI) given orally in 2 doses (10 mg/kg and 20 mg/kg) to horses were determined. The pharmacokinetic plasma-concentration profiles for 3MI (10- and 20-mg/kg dosages) in horses were represented by a 2 compartment open model with first-order absorption, as determined by nonlinear least-squares regression analysis. Absorption of 3MI at both dosages was rapid. Comparisons of the peak plasma concentrations, the postdistribution half lives, total clearances, and areas under the curve of the plasma-concentration profiles between the 10- and the 20-mg/kg dosages may indicate the presence of nonlinear or dose-dependent kinetics for 3MI in horses. PMID- 4037487 TI - Mechanism of renal excretion of creatinine by the pony. AB - Free-flow and stop-flow procedures conducted on 2 female and 2 testosterone treated castrated male ponies indicated that [14C]inulin and exogenous creatinine clearance values were the same. These results indicated that creatinine was neither reabsorbed nor secreted by the renal tubules and that exogenous creatinine clearance was an accurate method for determining glomerular filtration rate. As in other species which have been studied, endogenous creatinine clearance probably underestimated glomerular filtration rate because of the presence of noncreatinine chromogens in plasma. PMID- 4037488 TI - Pathophysiologic study of 3-methylindole-induced pulmonary toxicosis in immature cattle. AB - In 5 Friesian calves given 3-methylindole (3-MI) (100 mg/kg once a week for 8 weeks, except calf 4, given a 50 mg/kg dose on weeks 3 to 8), pulmonary function (PF) values and arterial blood gas tensions (PaO2 and PaCO2) were measured 24 hours after dosing was done and were correlated with clinical, biochemical, and pathologic changes. Three of the calves (No. 1, 2, and 3) showed acute respiratory distress syndrome 24 hours after the first 3-MI treatment, with a large increase in respiratory frequency, minute viscous work, and PaCO2 and a large decrease in tidal volume, dynamic lung compliance, and PaCO2. They died 36, 38, and 84 hours after dosing. Pulmonary function changes were compatible with the severe pulmonary edema and alveolar damage observed at necropsy. The 2 other calves, after they were given the 1st dose, showed only subacute respiratory distress syndrome with less severe changes in PF values recorded at 24 hours. Furthermore, they became progressively more tolerant to the 2nd, 3rd, and 4th weekly treatments, and showed base-line PF values after the 5th weekly treatment. Pathologic changes were not observed in lung biopsy material from these 2 animals at 2 and at 12 weeks after the 8th (or last) 3-MI treatment. PMID- 4037489 TI - Pathophysiologic effects of experimentally induced Fascioloides magna infection in sheep. AB - The pathophysiologic responses of 13 sheep inoculated orally with 100 metacercariae of Fascioloides magna were monitored for 4 months after inoculation. There were no differences in weight gains between these and a number of noninoculated control sheep throughout the experiment. Complete blood cell counts showed an increase only in the absolute number of eosinophils. Serum preparations (2 times a week) from 7 inoculated and 7 noninoculated sheep did not identify any significant changes in alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase, and gamma-glutamyl transferase activities. There were no changes in total bilirubin, BUN, creatinine, inorganic phosphorus, calcium, albumin, chloride, potassium, and sodium values. Four months after they were inoculated, all sheep were necropsied, and flukes were recovered. Gross lesions attributed to fluke migration were found in the liver and portal lymph nodes, diaphragm, lungs, kidneys, and spleen. Microscopically, liver lesions in inoculated sheep occurred in the portal areas, veins, and Glisson's capsule and were characterized by both active and chronic forms of inflammation. Abundant infiltrates of eosinophils and plasma cells often marked the portal areas. Endophlebitis, with or without thrombosis, was the predominate vascular lesion. The flukes recovered varied greatly in size (6.5 to 48.0-mm long) and demonstrated some sexual development, but none was sexually mature. PMID- 4037490 TI - Use of enzyme-linked immunosorbent assay for detection of antibodies to Brucella ovis in sheep: field trial. AB - An enzyme-linked immunosorbent assay (ELISA), using an autoclave-extracted soluble antigen, for the detection of serum antibodies to Brucella ovis in sheep was developed. The test seemed to be both sensitive and specific, on the basis of the control groups studied. The antigen showed no deterioration in prepared plates stored at -70 C for up to a year. The ELISA was used in conjunction with palpation of rams for epididymal lesions as a means to detect and control B ovis infection in a naturally infected flock. All rams were evaluated by the ELISA. At the time that the first blood sample was obtained, all positive and suspicious reactors were removed. With subsequent blood sample collections, only the positive reactors were removed. Brucella ovis was not isolated from any rams during the following year, and none of the mature breeding rams developed epididymal lesions. PMID- 4037491 TI - Effects of intraoperative irradiation on gastric and urinary bladder incisions in the dog. AB - Fourteen adult dogs of mixed breeding were given intraoperative irradiation (25 Gy) after surgical incisions were made into the greater curvature of the stomach and the ventral surface of the urinary bladder. Sequential biopsy samples were obtained 10 days to 180 days after surgical operation. All irradiated stomachs developed gastritis and persistent ulceration of the irradiated field. Microscopic changes induced by irradiation of both the bladder and stomach progressed from severe submucosal edema to severe submucosal fibrosis. A parallel progression of fibrinoid degeneration of the small blood vessels was seen in both organs. Severe gastric ulceration persisted up to 180 days after irradiation, although a degree of mucous neck cell and gastric gland regeneration did occur. Pathologic changes were less severe in the bladder than in the stomach. The bladder had greater resiliency and capability for healing and, in contrast to the stomach, showed a capability to reepithelialize the radiation-induced ulcers. Conclusions of this study are as follows: (a) the canine urinary bladder tolerated intraoperative radiation therapy after tissue resection better than did the canine stomach, (b) the combination of surgical operation and irradiation resulted in a more prolonged and complicated healing pattern than did either procedure alone, and (c) the introduction of a surgical procedure upon irradiated tissue within an undetermined time span relative to irradiation resulted in a similar pattern of disturbed healing. PMID- 4037492 TI - Echocardiographic and clinical effects of milrinone in dogs with myocardial failure. AB - Milrinone is a recently synthesized bypyridine compound with positive inotropic and arteriolar dilating properties in persons and experimental animals. To examine the efficacy and safety of milrinone to treat myocardial failure in dogs, dogs with myocardial failure were selected from the patient populations of 3 veterinary hospitals. Progressively increased dosages of milrinone, from 0.05 to 1.0 mg/kg of body weight, were administered over 14 days, and cardiac responses, as determined by M-mode echocardiography, and clinical responses were recorded. An effective dosage of milrinone was identified for each dog and administered for 4 weeks to evaluate the stability of the cardiac response. A randomized blinded study of drug vs nondrug capsule or nondrug elixer (designated placebo) was performed at the end of 4 weeks to eliminate possible effects of investigator bias or spontaneous regression of the disease. The duration of drug effect was determined by evaluating echocardiographic measurements of left ventricular function for 12 hours after drug administration. Echocardiographic evaluation of left ventricular function improved in dogs given milrinone. The effective dosage was between 0.5 and 1.0 mg/kg. Tolerance to milrinone did not develop during the 4-week study. In dogs given placebo during the randomized blinded study, echocardiographic values decreased significantly. Dogs that were given milrinone remained echocardiographically stable. During the study, 6 dogs improved clinically, 5 remained the same, 1 had a decrease in exercise tolerance, 1 died of severe heart failure, and 1 died of hypoadrenocorticism. Ventricular tachydysrhythmia was exacerbated in 2 dogs, but was not treated.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4037493 TI - Effect of collection time and exercise restriction on the prediction of urine protein excretion, using urine protein/creatinine ratio in dogs. AB - Nonproteinuric and proteinuric dogs were studied to determine whether the urine protein/creatinine ratio from a 24-hour urine sample could be used to predict urine protein excretion. Urine protein/creatinine ratios estimated from urine produced during daylight hours and from that produced during nighttime hours were compared to determine whether time of sample collection influenced the prediction of the urine protein excretion value. Urine protein/creatinine ratios in urine from male dogs were compared with those from female dogs to determine whether sex had an influence on the value. Hospitalized and nonhospitalized dogs were used to determine the effect of exercise restriction. The urine protein/creatinine ratio varied significantly between healthy and proteinuric dogs (P = 0.0001). It was not influenced by collection period or sex. Animals not confined to hospital cages had a significantly lower urine protein/creatinine ratio than did hospitalized animals confined to a cage (P = 0.003). PMID- 4037494 TI - Comparative pharmacokinetics and anesthetic effects of methohexital, pentobarbital, thiamylal, and thiopental in Greyhound dogs and non-Greyhound, mixed-breed dogs. AB - Pharmacokinetics and duration of anesthesia of methohexital, pentobarbital, thiamylal, and thiopental in Greyhound and non-Greyhound, mixed-breed dogs were compared. In all dogs evaluated, pentobarbital induced the longest duration of anesthesia and methohexital induced the shortest duration. Pharmacokinetics of pentobarbital and methohexital were similar in both groups of dogs. Thiobarbiturates induced longer anesthetic effects in Greyhound dogs than in mixed-breed dogs. Plasma thiobarbiturate concentrations remained above normal longer in Greyhound dogs than in mixed-breed dogs. Disposition of thiobarbiturates in Greyhound dogs was characterized by nonlinearity from 45 minutes to 8 hours after dosing. PMID- 4037496 TI - Plasma-glucose concentrations in dogs and cats before and after surgery: comparison of healthy animals and animals with sepsis. AB - Various surgical procedures were performed in healthy dogs and cats and in dogs and cats with sepsis. Plasma-glucose concentrations after surgery were usually increased over presurgical values. After surgery, cats had significantly higher plasma-glucose concentrations (P less than 0.05) than did dogs. Postsurgical concentrations for healthy dogs were between 100 to 200 mg/dl, whereas the concentrations for dogs with sepsis ranged from 66 to 356 mg/dl. Of 8 dogs with sepsis that developed postsurgical plasma-glucose concentrations of greater than 150 mg/dl, 4 (50%) died, whereas of 7 dogs with sepsis that developed postsurgical concentrations of less than 150 mg/dl, only 1 (14%) died; however, the difference between these 2 mortality percentages was not significant (P = 0.08). PMID- 4037495 TI - Effect of gastrin, histamine, serotonin, and adrenergic amines on gastroesophageal sphincter pressure in the dog. AB - In nonrestrained dogs that had not been given chemicals and that were in the fasted and fed state, gastroesophageal sphincter pressure (GESP) was measured; results were compared with GESP induced in the same dogs by drugs that modified activity at cholinergic, adrenergic, histaminic, and gastrin receptors. Atropine reduced GESP from 38.5 +/- 1.3 (mean +/- SE) and 55.5 +/- 2.0 mm of Hg to 11.3 +/ 2.0 and 14.5 +/- 2.4 mm of Hg in fasted and fed dogs, respectively. Histamine induced phasic contractions that were not affected by anticholinergics or cimetidine. Iphenhydramine eliminated the phasic contractions and reduced GESP to 18.2 +/- 3.9 mm of Hg. In fed dogs, diphenhydramine reduced GESP to 37.0 +/- 2.5 mm of Hg, but cimetidine did not. Pentagastrin induced increases in GESP that were inversely related to basal GESP. Pentagastrin given during histamine infusion eliminated histamine-induced phasic contractions. In fed dogs, metoclopramide increased GESP from 48.8 +/- 4.0 mm of Hg to 76.0 +/- 4.0 mm of Hg; this increment was eliminated by diphenhydramine. Administration of atropine after metoclopramide reduced GESP the same as for dogs given atropine alone. An adrenergic amine with only alpha-adrenergic effects induced phasic contractions, and an adrenergic amine with only beta-adrenergic effects reduced GESP. Blockers of alpha and beta effects did not change GESP in fed dogs. Domperidone induced phasic contractions that were eliminated by feeding. Serotonin increased GESP. Canine GESP may be maintained in fed dogs by chemicals interacting with cholinergic, histaminic, gastrin, and serotonin receptors, but not by chemicals interacting with adrenergic receptors. PMID- 4037497 TI - M-mode echocardiographic measurements in nonanesthetized healthy cats: effects of body weight, heart rate, and other variables. AB - Body weight, heart rate, and 19 M-mode echocardiographic variables were measured in 41 nonanesthetized healthy cats. Estimated limits were determined for the echocardiographic variables, and each variable was then correlated to body weight, heart rate, and the 18 other variables. A significant (P less than 0.05) positive correlation to body weight was found with aortic diameter, left atrial dimension, septal and left ventricular systolic and left ventricular diastolic wall thicknesses, and left and right ventricular diastolic and right ventricular systolic internal dimensions. Significant inverse correlation (P less than 0.05) to heart rate was found with body weight, left ventricular systolic and diastolic and right ventricular systolic internal dimensions, left atrial dimension, left atrial dimension to aortic ratio, mitral valve E point to ventricular septal separation, and left ventricular ejection time. Left ventricular shortening fraction in the short axis and velocity of circumferential fiber shortening were significantly correlated (P less than 0.05) to heart rate. Significant correlation (P less than 0.05) was also found between many echocardiographic variables. PMID- 4037498 TI - Change in M-mode echocardiographic values in cats given ketamine. AB - Determination was made of changes in heart rate and certain M-mode echocardiographic values in healthy cats given ketamine (3 to 5 mg/kg, IM). Heart rate and septal and left ventricular posterior wall thickness in diastole increased, and left ventricular internal diameter in diastole and shortening fraction decreased (P less than 0.02) after ketamine was given. With the adjustment for heart rate by analysis of covariance, left ventricular internal diameter in diastole, shortening fraction, and velocity of circumferential fiber shortening were significantly decreased (P less than 0.05) from base-line values. PMID- 4037499 TI - Fate of sodium pentobarbital in rendered products. AB - The fate of pentobarbital through rendering was evaluated by following a group of euthanatized animals through a commercial rendering facility. Samples of material were collected at various points in the rendering process, and assays for pentobarbital were conducted by an ultraviolet spectrophotometric method. The results indicated that the pentobarbital, or a closely related analogue, survived rendering without undergoing degradation. The pentobarbital was distributed approximately equally between the meat and bone meal and tallow fractions. If pentobarbital-euthanatized animals are processed along with other raw materials throughout a day's production, the likelihood of significant residues being present in rendered products is minimal. PMID- 4037500 TI - Mechanical properties of three orthopedic wire configurations. AB - An 18-gauge stainless steel wire was applied to a transverse fracture model to determine the antirotational effectiveness of cruciate, horizontal mattress, and simple interrupted interfragmentary wire configurations. The number of twists used to tighten the configuration and the distance from the fracture were compared in the cruciate and horizontal mattress patterns. In a 2nd experiment, the compressive forces generated at the fracture by cruciate and horizontal mattress configurations tightened with 1 and 2 twists were determined. The cruciate configuration was better than the horizontal mattress and simple interrupted configurations in preventing rotation (P less than 0.001). Increasing the distance from the fracture line to the wire holes decreased antirotational effectiveness. Tightening the cruciate and horizontal mattress configurations with 2 twists produced significantly greater compressions across the fracture line than did tightening with 1 twist (P less than 0.0001). PMID- 4037501 TI - Ultrastructural alterations of motor cortex synaptic junctions in Brown Swiss cattle with weaver syndrome. AB - An ultrastructural comparison was made between the motor cortex synapses of the brain of 4 adult Brown Swiss cattle with weaver syndrome and 2 healthy cattle (a Holstein steer and a Guernsey cow). Compared with the healthy cattle, the paramembranous densities at synaptic junctions of cattle with weaver syndrome had a decreased mean height of the presynaptic dense projections (P less than 0.001), had significantly smaller peak-to-peak distances (P less than 0.001), and had a significantly decreased mean thickness of the postsynaptic density (P less than 0.0001). These synaptic changes in cattle with weaver syndrome may be associated with clinical manifestations of the syndrome, such as impairment of transmitter release, instability of postsynaptic receptor sites, lesion-induced synaptic turnover from injury elsewhere in the CNS, or loss of a specific cell population of the motor cortex. PMID- 4037502 TI - Synergistic influence of Ostertagia ostertagi and Trichostrongylus axei on Ostertagia ostertagi larval inhibition and abomasal lesions in cattle. AB - Parasite-free 4-month-old calves were inoculated with Ostertagia ostertagi and/or Trichostrongylus axei followed 6 weeks later by increasing doses of O ostertagi for 8 weeks. Clinical signs of parasitism, fecal egg counts, and plasma pepsinogen concentrations were monitored, and gross lesions and parasite burdens were determined postmortem. Clinical signs of parasitism were not observed and weight gains were not affected in experimentally infected calves. In calves infected with O ostertagi, mean plasma pepsinogen concentrations were greater than for control calves and were diagnostically significant 4 weeks after inoculation and during the last 4 weeks of serial inoculations with O ostertagi. In calves that were given O ostertagi and T axei, abomasal pH was significantly increased, and abomasal lesions were more pronounced than in control calves or in calves inoculated with only O ostertagi or T axei. Abomasal lymph nodes were enlarged in all parasitized calves; other lymph nodes in the calves inoculated with both O ostertagi and T axei were usually smaller than in calves inoculated with only O ostertagi or T axei. Numbers of O ostertagi-inhibited larvae were small in all inoculated calves, but the percentage inhibition was significantly greater in calves inoculated with both O ostertagi and T axei. The percentage inhibition was 3.53% for the O ostertagi-inoculated calves and 7.07% for calves inoculated with both O ostertagi and T axei. These percentages indicated a synergistic effect of concurrent abomasal parasitism, whereas a synergistic effect on T axei worm burden was not observed. The low percentage of larval inhibition indicated that factors other than host resistance are involved in naturally occurring pretype II ostertagiosis. PMID- 4037503 TI - Persistence of encysted Toxoplasma gondii in tissues of equids fed oocysts. AB - Thirteen 6-month- to 13-year-old equids were each inoculated orally with 10,000 infective Toxoplasma gondii oocysts. The equids remained clinically normal. Equids were euthanatized on postinoculation days 33, 45, 90, 104, 120, 140, 162, 183, 197, 204, 211, 294, and 476. Their tissues were bioassayed for viable oocysts by feeding muscles to Toxoplasma-free cats and by inoculation of pepsin digests of 13 organs into mice. Using mouse inoculation, T gondii was recovered from tissues of the 9 equids euthanatized on each of postinoculation days 33, 45, 120, 140, 183, 197, 211, 294, and 476. Toxoplasma gondii was isolated from the tongue and intestines of 4 equids, from the heart of 3 equids, from thigh muscles, brain, and heart of 2 equids, and from the eye, lungs, and spinal cord of 1 equid. Muscles from 9 of 13 equids were infectious to cats, as evidenced by feline shedding of oocysts. Results indicate that T gondii can persist in edible tissues of living equids up to 476 days and that non-cooked horsemeat should not be fed to cats or eaten by human beings. PMID- 4037504 TI - Enzyme histochemical features of equine gluteus muscle fibers. AB - Gluteal muscle specimens were taken from 4 horses. From 1 of the 4 gluteal muscles, serial sections were prepared. Individual muscle fibers were identified and studied, using photomicrographs of sections stained by different enzyme histochemical methods. In specimens in which cytoplasmic soluble enzymes were studied, use was made of the semi-permeable membrane technique to hamper enzyme diffusion into reaction fluids. Enzymes involved in glycogenolysis, glycolysis, the tricarboxylic acid cycle, synthesis of reduced nicotinamide adenine dinucleotide phosphate, the pentose phosphate cycle, the alpha-glycerolphosphate shuttle, the respiratory chain, catabolism, and muscular contraction were studied. Some key enzymes of different metabolic pathways were also included. Each of 3 fiber types identified had distinct features. Type I fibers were characterized by a relatively strong aerobic capacity, compared with type IIA fibers, which were more glycolytic and had strong aerobic and moderate-to-strong anaerobic capacity. Type IIB fibers were characterized by a relatively low aerobic and a relatively high anaerobic capacity, and were glycolytic. Activities of phosphofructokinase, glyceraldehyde-3-phosphate dehydrogenase, lactate dehydrogenase, and alpha-naphtylesterase (nonspecific esterase) were so markedly different in the 3 fiber types that fiber typing was possible, aided by the demonstration of the activities of these enzymes. In type IIB fibers, the pentose phosphate cycle was more important than in the other fiber types. Except for the unexplained high alpha-naphtylesterase activity in type IIB fibers, catabolic enzymes were not active in healthy equine muscle fibers. PMID- 4037505 TI - Susceptibility of male white-tailed deer (Odocoileus virginianus) to Brucella ovis infection. AB - Infection with Brucella ovis was established by conjunctival instillation in 8 male white-tailed deer (Odocoileus virginianus). Infection was transient in young bucks, but persisted in bucks that were mature when inoculated. The deer were euthanatized and necropsied at various intervals after inoculation. Brucella ovis was recovered from a mature buck at necropsy on postinoculation day 429. Four deer had gross lesions and histopathologic changes of the epididymides. A mature noninfected buck confined for 7 months with an infected buck acquired infection and developed epididymal lesions. PMID- 4037506 TI - Relationship of serum concentrations of several enzymes to the porcine stress syndrome. AB - Serum enzyme concentrations were determined in 319 Hampshire pigs (approx 2 months of age). Significant positive correlations were found when creatine kinase (CK) concentrations were compared with lactate dehydrogenase and malate dehydrogenase values, but not when compared with aspartate aminotransferase or alanine aminotransferase values. In an additional study, a litter from a sow with high serum CK concentrations was observed at 2, 3, 4, and 5 months of age for serum CK concentrations. The CK concentration increased as the pigs aged, and soft exudative pork was found upon slaughter of the pigs at 5 months of age. It is believed that CK, lactate dehydrogenase, and malate dehydrogenase determinations in weanling pigs would have value for reducing the frequency of the porcine stress syndrome and soft exudative pork in breeding stock. If only a portion of the genetic carriers was removed, the effect would be considerable within a few generations. PMID- 4037507 TI - Attempted reactivation of contagious ecthyma in Dall sheep. AB - Dexamethasone was administered to 2 Dall ewes that had clinically recovered from contagious ecthyma in an attempt to reactivate contagious ecthyma in the sheep. Clinical signs of disease were not detected within 24 days after corticosteroid injection, and virus was not detected in tissues collected at necropsy. PMID- 4037508 TI - Effects of deficient and adequate dietary magnesium concentrations on body magnesium concentrations in wethers. AB - Effects of 2 dietary Mg concentrations (deficient and adequate: 0.04 and 0.12 g of Mg/100 g of dry matter, respectively) on body fluid and tissue Mg concentrations and performance of wether lambs were evaluated in a 28-day trial. Nine blood and 6 urine samples were collected from each wether. After 28 days, CSF and wool samples were collected, and diet, body fluids, and tissues were analyzed for mineral concentration. Diet effects on serum and urine Mg concentrations were noticed after day 3 (P less than 0.01; P less than 0.05, respectively). Mean serum and urine Mg concentrations for 6 sampling periods were correlated (r = 0.83, P less than 0.001; No. of samples = 12). The effect of dietary Mg on CSF Mg concentrations approached significance (P less than 0.10). Effects of diet on cardiac muscle, liver, and 3rd metatarsal bone Mg contents or hematologic criteria were not observed. Diet affected wool and kidney cortex Mg contents (P less than 0.02). Individual mean 28-day serum Mg concentration was correlated with wool Mg content (r = 0.73, P less than 0.05; n = 8) and with kidney cortex Mg content (r = 0.75, P less than 0.05; n = 8). Wethers fed low Mg diet excreted less urine Ca (P less than 0.001) and had slightly lower serum Ca and K values (P less than 0.10) than did wethers fed high Mg. Significant differences in cardiac muscle, liver, spleen, or kidney cortex Ca contents were not observed. Wethers fed low Mg diet consumed less dry matter and gained less weight (P less than 0.001) than did wethers fed high Mg diet. Body fluid and tissue macromineral concentrations of 1 wether with hypomagnesemic tetany are presented for prognostic and diagnostic purposes. PMID- 4037509 TI - Effects of canine distemper virus on natural killer cell activity in dogs. AB - An in vitro 51Cr-release assay was developed to detect the cytotoxicity of natural killer cells (NK) of canine peripheral blood mononuclear leukocytes to canine distemper virus (CDV) target cell membrane-bound antigens. Leukocytes from 23 young (greater than or equal to 1 week of age), CDV-naive gnotobiotic dogs could discriminate between noninfected control and CDV-infected Vero target cells. However, the amount of preinfection NK activity did not positively correlate with the ultimate outcome of the disease process when these same dogs were given virulent R252-CDV. Evaluation of preinfection and postinfection CDV specific NK activity indicated that infection-associated increases in cytolysis of CDV-infected or noninfected Vero targets did not occur. In vitro infection of peripheral blood leukocytes with CDV did not change the kinetics or magnitude of NK-mediated cytolysis of homologous virus-infected or other NK-susceptible target cells. PMID- 4037510 TI - Brain stem auditory-evoked responses in the dog. AB - Brain stem auditory-evoked responses (BAER) were recorded from 58 dogs that did not have a known history of hearing problems. The BAER wave forms had an overall mean amplitude approximately 3.0 microV and typically consisted of a series of 4 to 5 vertex-positive peaks (peaks I through V). When acoustic clicks having intensities of 60-dB hearing level (decibels relative to the subjective hearing threshold) were used as stimuli, peak I had a latency of 1.49 +/- 0.13 ms; peak II, 2.32 +/- 0.14 ms; peak III, 3.01 +/- 0.25 ms; peak IV, 4.22 +/- 0.27 ms; and peak V, 5.55 +/- 0.37 ms. Latency values were influenced by a number of nonpathologic factors, including stimulus intensity and the body temperature of the dog. As stimulus intensity was decreased, there was a lengthening of the latency of each peak coupled with a decrease in the overall amplitude of BAER. Decreases in rectal temperature caused a similar lengthening of peak latencies. Age may have an influence on BAER, but under the conditions of the present study, the effect was not significant. PMID- 4037511 TI - Clinical pharmacokinetics of amikacin in dogs. AB - After IV, IM, and subcutaneous injection of single dosages of amikacin (5, 10, and 20 mg/kg of body weight) in each of 4 dogs, the elimination kinetics of amikacin were determined. The pattern of urinary excretion and cumulative amount excreted unchanged in 24 hours were also determined. Amikacin had a short half life (approx 1 hour) that was independent of the dosage. Intravenous injection of 10 mg/kg gave apparent volume of distribution of 226 +/- 37 ml/kg and body clearance of 2.64 +/- 0.24 ml/min.kg (mean +/- SD, n = 4). Within 6 hours, greater than 90% of the antibiotic was excreted in the urine, regardless of the route of administration. For isolates of common bacterial species from the canine urinary tract, minimum inhibitory concentrations of amikacin, gentamicin, tobramycin, and kanamycin were determined in vitro. Cumulative percentages were approximately the same for urinary isolates of Escherichia coli, Proteus mirabilis, Pseudomonas aeruginosa, and coagulase-positive staphylococci that were susceptible (minimum inhibitory concentrations less than or equal to 32 micrograms/ml) to increasing concentrations of amikacin, gentamicin, and tobramycin, in vitro. Klebsiella pneumoniae was significantly more susceptible to amikacin than were the other bacteria evaluated. Widest variations in susceptibility to aminoglycosides were found with urinary isolates of streptococcal species. For dogs with normal renal function, an amikacin dosage of 10 mg/kg (IM or subcutaneously) is recommended every 8 hours for treatment of systemic infections, and every 12 hours for treatment of urinary tract infections caused by susceptible bacteria. PMID- 4037512 TI - Effect of povidone, povidone-iodine, and iodide on locomotion (in vitro) of neutrophils from people, rats, dogs, and rabbits. AB - The effect of the antiseptic povidone-iodine (P-I) on neutrophil locomotion was tested in vitro. Neutrophil migration into Micropore filters was significantly stimulated by P-I at concentrations between 0.03% and 0.005%. At higher concentrations (greater than or equal to 0.05%), a dose-dependent inhibition of neutrophil migration could be observed which was due to cytotoxic effects of P-I as shown by pyknosis and cell lysis. To analyze these effects, 2 components of P I (namely, povidone and iodide) were tested separately. In these tests, povidone induced a pronounced stimulation of neutrophil migration at concentrations similar to the stimulatory concentrations of P-I. Inhibition of neutrophil migration or cytotoxic effects of povidone was not observed, even when tested at high concentrations (5.0%). Iodide (as NaI or KI) was cytotoxic and strongly inhibited neutrophil migration when it was tested at concentrations greater than that likely to be present in the inhibitory concentrations of P-I. Stimulatory effects of iodide on neutrophil migration could not be observed when tested over a wide range of noncytotoxic concentrations. Free iodine was not tested, but was considered to be the toxic component by exclusion. The patterns of response were similar for neutrophils from the 4 species tested. Migration of rabbit neutrophils, however, was inconsistently and weakly stimulated by P-I or povidone. These data indicate that the widely used antiseptic P-I, depending on its concentration, can either stimulate or inhibit neutrophil migration. PMID- 4037513 TI - Stress and adaptational outcomes. The problem of confounded measures. PMID- 4037514 TI - Current NIH perspectives on misconduct in science. PMID- 4037515 TI - After the missiles. Sociopsychological effects of nuclear war. PMID- 4037516 TI - Biofeedback. Research, training, and clinical roles. PMID- 4037517 TI - Psychology and pediatrics: prospects for cooperative efforts to promote child health. Interview by Logan Wright. PMID- 4037518 TI - A room of their own. A proposal to renovate the Children's Bureau. PMID- 4037519 TI - Adult respiratory distress syndrome. Prognosis after onset. AB - In 88 patients with the adult respiratory distress syndrome, clinical, laboratory, cardiopulmonary, and demographic data collected on the day of onset of the syndrome were used to identify predictors of survivorship and mortality. Variables that individually were associated with mortality were then analyzed simultaneously by the Cox proportional hazards function and by multiple discriminant function using a step-up procedure. Four variables taken singly were significantly associated with mortality. These were the presence of less than 10% band forms on the initial peripheral blood smear, persistent acidemia with arterial pH less than 7.40, calculated HCO-3 less than 20 mg/dl, and blood urea nitrogen greater than 65 mg/dl. After eliminating those variables that did not contribute significantly to mortality in the presence of the others, only low band forms, low pH, and low HCO-3 were significantly associated with increased mortality. These findings illustrate the continued high mortality rate in the syndrome and indicate possible systemic aberrations that contribute to its severity. PMID- 4037520 TI - Pulmonary extraction of serotonin and propranolol in patients with adult respiratory distress syndrome. AB - Because injury to the pulmonary vascular endothelium is associated with the development of the adult respiratory distress syndrome (ARDS), we assessed the metabolic function of pulmonary endothelial cells by the measurements of the first-pass pulmonary extraction of [14C]serotonin and [3H]propranolol in 15 patients with ARDS and 15 patients at risk for developing ARDS. Serotonin extraction ratio was lower in patients with ARDS (0.85 +/- 0.10, mean +/- SD) than in patients at risk (0.91 +/- 0.04) (p less than 0.025), and both values were significantly reduced (p less than 0.005) when compared with a control group value (0.97 +/- 0.01). The decrease in serotonin extraction was correlated with the severity of ARDS (r = -0.67) (p less than 0.001) and with pulmonary function changes over time. Propranolol extraction ratio was decreased in patients at risk (0.66 +/- 0.11) (p less than 0.005) but not in patients with ARDS (0.75 +/- 0.11), when compared with those in the control group (0.81 +/- 0.03). Low values in patients at risk were restored to normal by continuous positive airway pressure breathing. We conclude that pulmonary extraction of serotonin, an index of pulmonary endothelial cell function, correlates with the severity of ARDS. PMID- 4037521 TI - Causes of mortality in patients with the adult respiratory distress syndrome. AB - This study analyzed the factors causing and contributing to death in patients with the adult respiratory distress syndrome (ARDS). Two hundred seven patients were prospectively identified as being at risk for development of ARDS. Forty seven patients developed ARDS, and the remaining 160 patients were used as a comparison control group. The severity of dysfunction in 8 organ systems and the presence of sepsis syndrome were determined by chart review after discharge or death. Sepsis syndrome was specifically defined by signs and laboratory tests reflecting infection or inflammation plus evidence of a deleterious systemic effect (hypotension, reduced systemic vascular resistance, or unexplained metabolic acidosis). Mortality was 68% in the ARDS group compared to 34% in the control group (p less than 0.005). Only 16% (5 of 32) of deaths in the ARDS group were from irreversible respiratory failure. Most deaths in the first 3 days after entry into the study could be attributed to the underlying illness or injury. The majority of late deaths were related to sepsis syndrome. Of the 22 patients with ARDS who died after 3 days, 16 (73%) met our criteria for sepsis syndrome. There was a sixfold increase in sepsis syndrome after ARDS compared with that in the control group (p less than 0.001). When sepsis syndrome preceded the ARDS, the abdomen was the predominant source, but when sepsis syndrome occurred after the onset of ARDS there was usually a pulmonary source. Our findings indicate that sepsis syndrome, rather than respiratory failure, is the leading cause of death in patients with ARDS. PMID- 4037522 TI - Chemotactic activity in bronchoalveolar lavage fluid from patients with adult respiratory distress syndrome. AB - Recent studies have shown that an influx of polymorphonuclear neutrophils into distal air spaces occurs early in the adult respiratory distress syndrome (ARDS). To study the mechanism of cell accumulation in this syndrome, we have evaluated the chemotactic activity in bronchoalveolar lavage fluid from patients with ARDS. Lavage fluid was obtained from 16 patients with ARDS within 24 h of endotracheal intubation and from 5 normal nonsmoking subjects. Lavage fluid from patients with ARDS had an average of 85% neutrophils on differential counts of cytologic preparations compared to less than 3% neutrophils for the control subjects. After removal of cells and lipids, lavage fractions of molecular weight greater than 10,000 daltons were chemotactic for human neutrophils in 14 of 16 patients, but no activity was seen with the normal lavages. Preliminary studies to identify the chemotactic factor were performed. PMID- 4037523 TI - Distribution of pulmonary blood flow in relation to atelectasis in premature ventilated lambs. AB - To investigate the ability of the preterm, ventilated lung to redirect blood flow away from atelectatic regions, we studied lambs with respiratory distress syndrome and spontaneous atelectasis or atelectasis caused by bronchial obstruction with a balloon catheter. Pulmonary blood flow distributions were measured by quantifying 15-mu, microsphere-associated radioactivity within multiple pieces of lung. Lambs with well aerated or very atelectatic lungs had relatively uniform blood flow/gram lung in all pieces of lung. Blood flow was much less uniform in lungs with both aerated and atelectatic regions. In 9 lambs with spontaneous atelectasis that included 25 +/- 5% (mean +/- SE) of the lungs by weight, blood flow was 29 +/- 4% less to atelectatic than to aerated lung volumes (p less than 0.01). In 5 lambs with well-aerated lungs, 18 +/- 3% of the lung by weight was made atelectatic by balloon occlusion of a major lower lobe bronchus. There was a 44 +/- 11% decrease in blood flow to the atelectatic lung segments. These studies document the ability of the lung of the premature, ventilated lamb to shunt pulmonary blood flow away from atelectatic lung volumes. PMID- 4037524 TI - The influence of hypoxemia on tritiated digoxin plasma kinetics and tissue distribution in the conscious dog. AB - The goals of this study were to document the effect of hypoxemia on the distribution of digoxin in conscious dogs. For this purpose, 6 beagles were exposed to air and 6 others to an atmosphere containing 10% O2, to generate a PaO2 equal to 46.3 +/- 0.3 mmHg (mean +/- SEM). The animals received 25 micrograms/kg of digoxin containing 2.17 micrograms/kg of 3H-digoxin, and then blood and urine samples were collected over the next 48 h, at which time they were killed to determine digoxin concentrations in several tissues. Five additional beagles were used to assess the influence of hypoxemia on the blood perfusion to these tissues using radioactive microspheres. The results, expressed as digoxin equivalents, indicated that hypoxemia increased the digoxin apparent volume of distribution (2.85 +/- 0.10 versus 2.01 +/- 0.11 L/kg; p less than 0.001) and the time required to achieve this distribution (9.7 +/- 1.4 versus 2.6 +/- 0.3 h; p less than 0.01). As digoxin clearance was not influenced by hypoxemia, the half-life was increased from 25.2 +/- 1.5 to 33.4 +/- 1.3 h (p less than 0.01). With hypoxemia, digoxin concentrations increased significantly in the brain and diaphragmatic muscle, but only marginally in other organs, including the heart, the latter despite a significant increase in blood flow. It is concluded that hypoxia does change digoxin disposition but does not increase digoxin heart concentrations. Therefore, factors other than changes in digoxin plasma kinetics and heart distribution may be responsible for the decrease in digitalis tolerance during hypoxemia. PMID- 4037525 TI - Pharmacokinetic studies on antituberculosis regimens in humans. I. Absorption and metabolism of the compounds used in the initial intensive phase of the short course regimens: single administration study. AB - The absorption and metabolism of streptomycin, isoniazid, rifampicin, and pyrazinamide were evaluated after administration of each drug alone and in combination. In the combination sessions, isoniazid, rifampicin, and pyrazinamide were administered orally, either individually or in a single fixed-ratio triple preparation. The results have shown that the pattern of absorption and metabolism (acetyl-isoniazid, desacetyl-rifampicin, and pyrazinoic acid) found after administration of each drug alone did not differ from that found after administration of the drugs in free and fixed combination. The 3 orally administered drugs given in a fixed combination resulted in a reduction of the order of 50% of the total number of tablets to be ingested. PMID- 4037526 TI - Tuberculin conversions in Indochinese refugees. An assessment of boosting and anergy. AB - Indochinese refugees entering the United States have a high rate of tuberculosis and tuberculin reactivity. In addition, several investigators have noted that a large number of refugees with initial tuberculin tests that are "not significant" change to "significant" reactions when retested within 8 wk. This "conversion" phenomenon has been reported in 21 to 43% of refugees and has been unexplained by antigen, testing, demographic, or exposure risk factors. A prospective evaluation of 218 refugees, conducted to assess the role of anergy and boosting, confirmed earlier findings, with 52% of 118 persons with initial tuberculin reactions that were "not significant" developing "significant" reactions on subsequent testing. Anergy, as measured by nonreactivity to mumps and candida skin tests, was not found to be a contributing factor, as few refugees were anergic and as rates of anergy did not differ significantly among refugees with different responses to tuberculin. Boosting, however, played a major role in explaining the "conversions," as 59% of persons who changed to "significant" tuberculin tests did so when retested with tuberculin at 1 to 3 wk. "Delayed" boosting rather than incubating disease or anergy appeared to be the most likely explanation for the remaining "conversions" that occurred on a third PPD test conducted at approximately 8 wk. If the "conversion" phenomenon is due to boosting, it remains to be seen whether the boosting is a result of previous exposure to Mycobacterium tuberculosis or to other, nontuberculous mycobacteria. PMID- 4037527 TI - Sleep-wake complaints in patients with sleep-related respiratory disturbances. AB - The relation of sleep complaint to sleep continuity and respiratory disturbance was studied by comparing 2 series of patients with sleep apnea, one group complaining of insomnia and the other of excessive daytime sleepiness. On polysomnographic evaluation, patients with insomnia complaints had fewer and shorter, primarily central, apneas that had little hypoxemic effects. Patients with excessive sleepiness complaints had more and longer, primarily obstructive, apneas that produced significant hypoxemia. Sleep of the excessively sleepy patients was lighter and longer, whereas that of the patients with insomnia was characterized by more wake time before and after sleep onset. The excessively sleepy patients were objectively sleepy on a test of daytime sleepiness, whereas patients with insomnia were alert. PMID- 4037528 TI - Patterns of accumulation of platelets and neutrophils in rat lungs during exposure to 100% and 85% oxygen. AB - The influx of leukocytes into the lung during hyperoxic exposures has been suggested as a significant contributor to alveolar injury because, when activated, they can cause damage by producing oxygen radicals and releasing hydrolytic enzymes. To better understand the relationship between hyperoxic injury and inflammatory responses, morphometric methods were used to quantitate changes in alveolar capillary blood components of rats exposed to 100% and 85% oxygen. After 40 h in 100% oxygen the absolute volume of platelets in the capillary bed increased 78% and there was a 111% increase in the total endothelial cell surface area covered by platelets. There were no significant changes in these parameters for neutrophils until 60 h of exposure of 100% O2. At this point, both the absolute volume and the endothelial surface area covered by neutrophils increased more than threefold. After 3 days in 85% oxygen absolute platelet volume was almost doubled and the surface area covered by platelets increased 79%. No neutrophil increases occurred until 5 days exposure to 85% oxygen, and both absolute volume and surface area dropped to less than control values after 7 days of exposure. The appearance of platelets prior to an influx of neutrophils during both hyperoxic exposures suggests that the initial endothelial cell injury results from an increased intracellular production of oxygen radicals rather than being due to oxygen radicals produced by leukocytes. Endothelial cell membrane changes were associated with the initiation of platelet accumulation in the capillary bed. Platelet components released during platelet activation may be important mediators for the subsequent neutrophil influxes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4037529 TI - An immunohistochemical characterization of rhesus monkey respiratory secretions using monoclonal antibodies. AB - A series of 12 monoclonal antibodies was made against mucous and serous components of rhesus monkey trachea. These antibodies were used to localize secretory products in the respiratory epithelium by immunohistochemical methods. Mucous cells of the tracheal surface epithelium and submucosal glands were shown by histochemical methods to be a homogeneous population containing periodate reactive sulfated glycoconjugates. Immunohistochemical staining using the monoclonal antibodies on glycol methacrylate sections serial to those stained histochemically revealed a more antigenically heterogeneous population of secretory cells. Four distinct staining patterns were observed with the 12 monoclonal antibodies. Eight antibodies reacted with most, but not all, mucous and serous cells. Two antibodies recognized subpopulations of secretory cells. One antibody stained tracheal mucous cells with a concentration of reaction product on the luminal border, and one antibody stained only serous cells within the glands. Ten of the 12 antibodies were shown to react in an ELISA with the high molecular weight void volume containing mucous glycoproteins separated on a Sepharose CL-4B gel filtration column. None of the antibodies recognized blood group antigens. We conclude: (1) that production of a large panel of monoclonal antibodies to respiratory tract mucins from primates is feasible, (2) that the monoclonal antibodies will recognize epitopes on biochemically identifiable glycoproteins, and (3) that the intracellular mucous products of tracheal secretory cells exhibit greater heterogeneity than is detectable by conventional histochemistry. PMID- 4037530 TI - The lipid-laden alveolar macrophage as a marker of aspiration in parenchymal lung disease. AB - We prospectively evaluated lower respiratory secretions obtained by bronchoalveolar lavage and stained with Oil-Red-O in patients with a variety of parenchymal diseases and in normal subjects. Our subjects included aspirators (n = 9), nonaspirators (n = 40), and normal subjects (n = 9). By grading the amount of intracellular Oil-Red-O per 100 alveolar macrophages, we computed a semiquantitative, lipid-laden alveolar macrophage index. The mean index for aspirators of 207 +/- 80 was significantly greater than the mean indexes of nonaspirators (121 +/- 97, p less than 0.02) and normal subjects (0.6 +/- 1.7, p less than 0.001). An index of greater than or equal to 100 had a sensitivity and negative predictive value of 100% each, a false negative rate of 0%, and a specificity of 57%. We conclude that (1) the mere presence of lipid-laden alveolar macrophages in lower respiratory secretions is a nonspecific marker of parenchymal lung disease; (2) the computation of a lipid-laden alveolar macrophage index may be helpful in excluding aspiration as a cause of parenchymal lung disease. PMID- 4037531 TI - Lung growth and development in anencephaly and hydranencephaly. AB - Significant qualitative and quantitative differences were observed in the lungs of 4 of 6 infants with anencephaly and hydranencephaly. In 3 of 4 of them, the findings were explicable on the basis of the presence of associated congenital anomalies, and in the fourth there was polyhydramnios. The infants with normal lungs did not have associated congenital abnormalities. The absence of the pituitary did not correlate with the degree of development of the lungs. Studies of lung growth in anencephaly and hydranencephaly must clearly note the presence of associated anomalies because anencephaly/hydranencephaly per se may not cause pulmonary hypoplasia in the majority of cases. The most satisfactory assessment in evaluation of lung growth and development was obtained by combining morphologic findings with more than one morphometric parameter. Radial count estimation alone was found to be a poor predictor of lung maturity (morphologic age) in hypoplastic lungs. Radial count and fixed lung volume together provide a better assessment of lung growth and development than does the ratio of lung weight to body weight, which is of use only if severely depressed. The terms immaturity and hypoplasia of the lungs are not necessarily synonymous. PMID- 4037532 TI - Amphotericin B causes aggregation of neutrophils and enhances pulmonary leukostasis. AB - The influence of amphotericin B (AmB) on the aggregation of polymorphonuclear leukocytes (PMN) was examined by means of in vitro aggregometry as well as in an in vivo model of pulmonary leukostasis (PL). The AmB caused a dose-dependent aggregation of PMN that was partially blocked by addition of serum to the drug prior to its reaction with the PMN. No aggregation of PMN was seen after the addition of nystatin, a similar polyene antibiotic. In vivo studies were conducted in rabbits, where PL was induced by an intravenous infusion of zymosan activated plasma (ZAP) or phorbol myristate acetate (PMA), and the degree of resulting leukostasis was expressed as the number of PMN per high power field (HPF). Animals in the control group had 6 +/- 3 PMN/HPF. This number increased to 12.4 +/- 5.6 when ZAP was infused and postmortem examination was performed 1 h later and to 17.4 +/- 4 if the examination was performed after 24 h. These numbers increased more than twice when AmB (1 mg/kg) was infused together with the ZAP. Increased PL after the infusion of ZAP and AmB was not attenuated by prior administration of methylprednisolone (30 mg/kg) to the animals. Infusions of AmB per se caused no significant PL but did cause increased pinocytosis in the pulmonary endothelium. Enhancement of PL by AmB was also examined in a model of PMA-induced PL.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4037533 TI - Short-term regional clearance of an inhaled submicrometric aerosol in pulmonary fibrosis. AB - Regional clearance of submicrometric aerosol during 5 days was studied in control hamsters and in those with diffuse interstitial pulmonary fibrosis. Fibrosis was induced by treatment with bleomycin (1.6 U/kg) and oxygen (70% for 72 h) 80 days earlier. Diseased and control animals were exposed for 30 min to an insoluble colloidal 198Au aerosol (AMAD, 0.62 micron; sigma g, 1.35). Five diseased and 6 control animals were killed immediately (Day 0); 6 diseased and 6 control animals were killed 5 days later (Day 5). All lungs were excised, dried at TLC, sliced into 1-mm sections, and dissected into pieces. When compared with deposition in Day 0 control lungs, 26.3% of the particles had been cleared 5 days after exposure from the control lungs. Diseased animals cleared 44.6% of the particles (p less than 0.05, compared with Day 0 diseased animals). Examination of regional clearance on the basis of lobar differences, apex to base levels, and presence of airways also reflected increased clearance in the fibrotic animals. The parenchymal distribution of particle retention at Day 0 was less uniform in the fibrotic animals than in the control animals and was not significantly altered after 5 days of clearance in either group. Particle clearance may be greater in diseased lungs because of accelerated alveolar-bronchiolar transport of particles or particle-containing macrophages. PMID- 4037534 TI - Lung function and exercise performance in smoking and nonsmoking asbestos-exposed workers. AB - Evaluation of impairment caused by exposure to an occupational toxin can be complicated by additional exposure to other injurious agents. Because cigarette smoking is common and cigarettes are implicated in obstructive lung disease and cardiovascular diseases, we assessed the contribution of smoking to functional abnormalities in a group of asbestos-exposed shipyard workers. Seventy-three workers who never smoked were paired with 73 current smokers by age and asbestos exposure. Pulmonary function and performance during cycle incremental exercise were compared between the 2 groups. Nonsmokers had significantly higher VC, FEV1, FEV1/VC, and diffusing capacity for carbon monoxide than did smokers. Only 3 of the 73 nonsmokers but 23 of the 73 smokers had a FEV1/VC below the 95% confidence limit of predicted value. The FEF25-75%, on the other hand, failed to identify additional subjects with obstruction not found by the FEV1/VC. During exercise, despite no difference in maximal heart rate, the maximal O2 uptake (VO2max) and oxygen-pulse were lower among smokers. In addition, smokers more frequently had abnormal AaPO2 at maximal exercise. Of 33 smokers who had a VO2max less than 80% of predicted, 16 were judged to have cardiac disease, whereas only 2 appeared to be limited by obstruction. Only 15 of the 73 nonsmokers had a VO2max less than 80%. We conclude that cigarette smoking was the major contributing factor to the obstructive lung disease observed in asbestos workers, and it also had a strong influence on the occurrence, nature, and magnitude of exercise limitation. The history of cigarette smoking has an important effect on the assessment of impairment from asbestos. PMID- 4037535 TI - Respiratory effects of photochemical oxidant air pollution in exercising adolescents. AB - Healthy volunteers 12 to 15 yr of age (46 boys, 13 girls) were exposed to purified air and to smoggy Los Angeles ambient air on different occasions. The studies were performed in random order approximately 2 wk apart. They included 1 h of continuous bicycle exercise (mean ventilation, 32 L/min) plus brief warm-up and cool-down periods. Symptoms and forced expiratory performance were recorded preexposure in purified air, immediately postexposure, and after 1 h recovery in purified air. Mean exposure temperature was 32 degrees C, and mean relative humidity was 45%. In ambient exposure, pollutant concentrations averaged 0.144 ppm for ozone and 153 micrograms/m3 for total suspended particulates. Group mean FEV1 decreased during ambient exposure (p less than 0.01) and only partially recovered during the following 1 h. Unlike adults studied previously, this subject group reported no significant increase in respiratory symptoms accompanying changes in FEV1. Adolescents may be less aware of early respiratory irritation by oxidants and thus more at risk from ambient exposures than are adults. PMID- 4037536 TI - Increases in intrathoracic pressure do not explain the rise in left ventricular end-diastolic pressure that occurs during exercise in patients with chronic obstructive pulmonary disease. AB - During exercise, patients with chronic obstructive pulmonary disease (COPD) increase their pulmonary arterial wedge (Ppaw) and left ventricular (LV) end diastolic pressures more than normal control subjects. The increase in pressure is commonly attributed to an increase in intrathoracic pressure (Pit). However, mean esophageal pressure (Pes) does not increase with supine exercise in patients with COPD. Because changes in Pes may not represent changes in Pit when recorded in the supine position, we measured Ppaw and Pes during upright exercise in 8 patients with severe air-flow limitation (mean +/- SD) FEV1, 0.88 +/- 0.27 L secondary to COPD and no history or electrocardiographic abnormalities suggesting a previous myocardial infarct, history of angina, evidence of systemic hypertension, or use of cardiac medications. In addition, all patients completed a progressive exercise test to exhaustion without angina or ST segment changes, and all had normal LV function at rest assessed by equilibrium radionuclide ventriculography. The Ppaw increased a mean of 7.2 +/- 4.3 mmHg, whereas Pes increased a mean of only 1.3 +/- 1.6 mmHg. By multiple linear regression analysis, Ppaw was significantly associated with the work level performed (p less than 0.01), but had no significant association with Pes (p greater than 0.1). The change in Ppaw could not be attributed to changes in Pes. If changes in Pes during upright exercise are representative of changes in Pit or juxtacardiac pressure, a rise in Pit does not explain the exercise-induced increase in Ppaw and LV end-diastolic pressure that occurs in patients with COPD. PMID- 4037537 TI - Pattern of inhalation of tobacco smoke in pipe, cigarette, and never smokers. AB - There is controversy on whether both primary and secondary pipe smokers do inhale tobacco smoke. We studied inhalation of tobacco smoke in 6 primary and 6 secondary pipe smokers and compared it with that in 20 cigarette smokers and 11 never smokers. Respiratory movements were assessed with inductive plethysmography, nasal flow through measurements of nasal pressure, oral flow with an oral thermistor, puffing through pressure measurements in the cigarette holder or the pipe, and upper airways by fluoroscopy. In all pipe smokers except 1, breathing and smoking appeared as independent activities. The former was exclusively nasal, whereas the latter was exclusively oral. Smoke was sucked and puffed by a to-and-fro movement of the tongue sliding along the soft palate. The oropharyngeal isthmus was closed (or only intermittently opened) by the apposition of the soft palate and the tongue, thus preventing overt inhalation of smoke. In most cigarette smokers, smoking interfered with the breathing route. Once smoke was sucked into the mouth, the oropharyngeal isthmus opened and inspiration proceeded through both mouth (with inhalation of smoke) and nose. Cigarette smoking interfered also with the evenness of ventilation. Never smokers avoided inhalation by oropharyngeal closure followed by oral expiration. We conclude that the oropharyngeal isthmus is the essential gate controlling smoke inhalation. Most secondary pipe smokers are able to change their smoking pattern and avoid overt inhalation when switching from cigarette to pipe smoking. The inhalation pattern appears to be acquired in the course of the smoking history. PMID- 4037538 TI - Acute effects of 0.12 ppm ozone or 0.12 ppm nitrogen dioxide on pulmonary function in healthy and asthmatic adolescents. AB - Adolescent asthmatic subjects have been shown to be much more sensitive than healthy adolescents to the inhaled effects of sulfur dioxide. To test whether similar adolescent asthmatics are more sensitive to other common ambient air pollutants, 10 healthy and 10 asthmatic adolescent subjects were exposed for 60 min to filtered air, 0.12 ppm ozone (O3), and 0.12 ppm nitrogen dioxide (NO2) on separate days at rest. The following pulmonary functional values were measured before, at 30 min, and after 60 min of exposure: peak flow, total pulmonary resistance (RT), thoracic gas volume at functional residual capacity (FRC), maximal flow at 50 and 75% of expired vital capacity (Vmax50 and Vmax75), and forced expiratory volume in one second (FEV1). Following 60 min of exposure at rest to low concentrations of O3 or NO2, there were no consistent significant functional changes in either healthy or asthmatic adolescent subjects. There also were no measurable differences between the 2 groups. PMID- 4037539 TI - Effect of chronic lung disease on the perception of added inspiratory loads. AB - The perceived magnitude of externally added loads to breathing was estimated in 10 normal subjects and 10 patients with chronic lung disease (5 obstructive, 5 interstitial disorders) to determine if chronic mechanical abnormalities of the respiratory system are accompanied by changes in the perception of dyspnea. Flow rates and tidal volumes were varied to assess the effect of altered patterns of breathing. With added resistive loads, the perceived magnitude increased as both resistance and the flow rate increased. With elastic loads the perceived magnitude increased as both elastance and tidal volume increased. In all subjects, perceived magnitude of added loads was most directly related to the inspiratory pressure used to overcome the load. Although the exponent for the power function relationship between perceived magnitude and the physical magnitude of the load was affected by the subject's age, there was no difference between the patients studied and the age-matched normal subjects. The results indicate that the sensation associated with added loads to breathing is the same in patients with chronic lung disease as in normal subjects. Also, they suggest that the altered pattern of breathing in patients with chronic lung disease is a behavioral adaptation to minimize respiratory distress. PMID- 4037540 TI - Differential inhibition of bronchoconstriction by the calcium channel blockers, verapamil and nifedipine. AB - Recent studies have demonstrated that the calcium channel blocking agents can inhibit experimentally induced bronchoconstriction in asthmatics, but their protective action has been variable. To clarify the influence of stimulus intensity and choice of calcium blocker on these reported differences in outcome, we performed noncumulative thermal stimulus-response curves using isocapnic hyperventilation of cold air in 8 asthmatics. Subjects received pretreatment with orally administered nifedipine (20 mg), intravenously administered verapamil (10 mg bolus followed by a continuous infusion), or appropriate placebos in a randomized, double-blind fashion. Verapamil afforded no consistent protection against the thermal challenges, whereas nifedipine significantly blunted the bronchoconstrictor response to stimuli of low (p less than 0.02) and middle (p less than 0.03) intensity. At the highest thermal burden, the effect of nifedipine was inconsistent and not significantly different from that of placebo. These results indicate that the protection from bronchoconstriction afforded by the calcium channel blockers depends on the choice of agent and the intensity of the bronchoconstricting stimulus, and they raise the possibility that the contribution of transmembrane calcium ion influx to the pathogenesis of bronchoconstriction may vary according to stimulus intensity. PMID- 4037541 TI - The contributions of rib cage and abdominal displacements to the hyperinflation of acute bronchospasm. AB - To quantitate the relative contributions of rib cage and abdomen to the hyperinflation of asthma, we examined chest wall movements during histamine induced bronchospasm in 7 male asthmatic subjects. A reduction in FEV1 of 28.1 +/ 4.5% (mean +/- 1 SE) was associated with an increase in functional residual capacity (FRC) of 0.99 +/- 0.19 L, as measured by spirometer. Similar increases in FRC (0.91 +/- 0.18 L) were obtained using a DC respiratory inductive plethysmograph (RIP). The absolute error of measurement of delta FRC by RIP, compared with that by the spirometer, was 23.0 +/- 1.9%. The delta FRC by RIP was slightly less than by spirometer, as indicated by a net positive error of 7.2 +/- 7.3%. Increase in the volume of the rib cage, measured by RIP, usually accounted for the major change in FRC (75%). Even though the contribution of rib cage displacement to delta FRC ranged from as little as 30% to as much as 100% of the change in individual subjects, it was correlated with the rib cage contribution to the tidal breath prior to bronchoconstriction. We conclude that the relative contributions of rib cage and abdominal displacements to the volume of hyperinflation during mild to moderate acute induced bronchoconstriction are quite variable, but they can be predicted from the relative contributions of these compartments to tidal breathing prior to bronchoconstriction. PMID- 4037542 TI - Accuracy of two ear oximeters at rest and during exercise in pulmonary patients. AB - The accuracy of 2 ear oximeters (Hewlett-Packard 47201A and Biox IIA) was evaluated at rest and during exercise in 116 pulmonary patients. Ear oximetry measurements were compared with arterial oxygen saturation (SaO2) measured from simultaneous arterial blood samples. When used according to the manufacturer's instructions for stabilization during exercise testing, both oximeters demonstrated comparable accuracy in estimating arterial blood SaO2 both at rest and during exercise in these patients (95% confidence limits, 2 SEE = +/- 4 to 5%). The oximeters were more accurate in measuring a change in SaO2 from a previous reading (95% confidence limits, 2 SEE = +/- 2.5 to 3.5%). COHgb levels greater than 4% and dark skin pigmentation appeared to decrease the accuracy of ear oximetry measurements. Within the limitations of accuracy, both ear oximeters may be useful for clinical exercise testing in pulmonary patients. PMID- 4037543 TI - Upper airway artifact in respiratory impedance measurements. AB - When studying respiratory impedance by forced oscillations, part of the flow measured at the mouth is lost in upper airway wall motion and does not enter the trachea. The corresponding error was studied in 10 normal subjects and 8 patients with chronic obstructive pulmonary disease (COPD) by measuring respiratory impedance with the cheeks unsupported, with the cheeks supported, and when upper airway wall motion was simultaneously measured with a head plethysmograph, and corrected for. In normal subjects, wall motion had little influence on respiratory resistance but, whether the cheeks were supported or not, increased the resonant frequency (p less than 0.05) and respiratory compliance (p less than 0.001) and decreased respiratory inertance (p less than 0.001). In patients with COPD, average resistance from 4 to 30 Hz was significantly lower when the cheeks were not supported (3.32 +/- 0.57 cm/H2O X L-1 X s; m +/- SD) than when they were (4.59 +/- 0.73, p less than 0.01) and when the data were corrected (5.41 +/- 1.14, p less than 0.001). Moreover, resistance increased with increasing frequency when wall motion was corrected for and decreased when it was not. Upper airway wall motion also tended to increase resonant frequency and decrease inertance in patients. The data show that supporting the cheeks does not prevent large errors on respiratory impedance and derived parameters, especially in obstructive patients; accurate measurements require that airway wall motion be evaluated and corrected for. PMID- 4037544 TI - The use of the pediatric fiberoptic bronchoscope in adults. AB - Standard fiberoptic bronchoscopes with external diameters of more than 4.5 mm are commonly used to diagnose pulmonary diseases in adults. A smaller bronchoscope with an external diameter of 3.5 mm has been in use to examine pediatric airway disorders. Three adult patients, 2 with hemoptysis and 1 with cough, when examined using the standard fiberoptic bronchoscope, had nondiagnostic findings. Subsequent examination using the pediatric fiberoptic bronchoscope revealed endobronchial lesions in all 3 patients. On the basis of the findings of pediatric bronchoscopic examination, it was possible to provide appropriate therapeutic decisions, which may not have resulted from the standard bronchoscopic examinations. The smaller external diameter of the pediatric bronchoscope will enable the bronchoscopist to detect endobronchial lesions in smaller airways that cannot be visualized by the standard fiberoptic bronchoscopes. PMID- 4037545 TI - Effects of acute bronchoconstriction on respiratory activity in patients with COPD. PMID- 4037546 TI - Learning style analysis in surgical training. AB - Learning style analysis is being used at many educational levels to individualize the instructional process. The Kolb Learning Style Inventory (LSI) in particular has been employed to determine the learning preferences of medical students and physicians in family practice, internal medicine, and anesthesiology. This investigation was undertaken to discover whether there exists a characteristic learning profile for surgery as a specialty. The Kolb LSI was administered to 39 surgical personnel. Kolb's Converger was the preferred learning style type of the study group (46%). Accommodator (26%) and Assimilator (20%) were next, followed by Diverger (8%). These results suggest that there is an identifiable surgical learning style that can provide a referential basis for teaching and counseling during residency training. PMID- 4037547 TI - Acute jejunogastric intussusception. AB - Acute jejunogastric intussusception is a rare complication following gastric surgery. Three patients were treated for this condition during the past 15 years. Common presenting manifestations are vomiting, hematemesis, upper abdominal pain, and palpable abdominal mass within the left hypogastrium. The diagnosis is established by gastroscopy or upper gastrointestinal radiographs. Four categories of classification are described. Optimal operative management consists of prompt laparotomy. Manual reduction of the intussusception is followed by resection of compromised bowel. Procedures to prevent recurrence are individualized. PMID- 4037548 TI - Sigmoid volvulus in children. AB - Volvulus of the sigmoid colon is rare in children. The authors have reviewed a total of 29 cases, including five from our institution. The most common clinical picture is crampy abdominal pain and abdominal distention. In contrast to adults, in children plain abdominal films will often not yield a diagnosis. Barium enema examination can be done to locate the obstruction. Nonoperative reduction was successful in 27 per cent of all reported cases, while operative treatment was necessary in 69 per cent of pediatric patients reported. Recurrence following derotation by any means was rare. However, adequate long-time follow-up is lacking. From available data, it seems that in most cases resection is not necessary. Primary resection may be indicated for recurrence or if the bowel is compromised. Mortality was 14 per cent, occurring in poor risk patients, the very young, and patients with associated anomalies. A redundant sigmoid may undergo intermittent torsion over a period of years, making diagnosis difficult. At laparotomy, these patients have scarred striae on the sigmoid mesocolon. PMID- 4037549 TI - Stercoral perforation of the colon. Concepts of operative management. AB - Stercoral perforation of the colon is a direct result of ischemic pressure necrosis by a stercoraceous mass. In over 90 per cent of cases, the perforation will involve either the sigmoid or rectosigmoid colon and is consistently centrally located within a region of mucosal ulceration of varying diameter and magnitude. A review of 33 surgically treated cases from the literature along with four cases presented here, support resection, end colostomy, and either mucous fistula or Hartmann's procedure as the operation of choice with the lowest operative mortality (23%) when compared to those patients treated by either loop colostomy or exteriorization (71%) or proximal colostomy with plication of the perforation (44%). Irrigation of the distal rectal segment as that for penetrating rectal injury is also recommended. PMID- 4037550 TI - A community experience with entericovesical fistulas. AB - A community experience with entericovesical fistulas is presented as well as a review of the literature. The series of 16 cases illustrates that this complication continues to present challenges in diagnosis and treatment. Diverticulitis is by far the most common primary disease process leading to the formation of entericovesical fistulas and the controversy involved in the surgical management of diverticulitis carries over to the management of this rare complication of the disease. It is felt that a one-stage procedure can often be accomplished and should be the procedure of choice in well-prepared, electively operated patients. When multiple stages are required, the two-stage approach is recommended. Familiarity with the proper treatment and a greater index of suspicion for this complication will lead to more acceptable management of patients with entericovesical fistulas. PMID- 4037551 TI - Primary carcinoma of the gallbladder. AB - Sixty-five Japanese patients with primary carcinoma of the gallbladder treated in the Department of Surgery I at Kyushu University from 1965 through 1982 were reviewed. Forty-one patients had histologically proven primary carcinoma and the other 24 patients were diagnosed by laparotomy and/or combination of several diagnostic procedures. The female to male ratio was 1.5 to 1. The peak incidence was at the ages of 60-69 years for both sexes. Gallstones were found in 53 per cent of resected patients and were demonstrated in 58 per cent of unresected patients by ultrasonography. Laparotomy was performed on 50 patients and the tumor could be removed in 15 patients. Resection could be done in only one of 18 patients correctly diagnosed. Fourteen of 15 patients who underwent resection had been diagnosed as cases of benign lesions. Curative resections were feasible in six of 15 patients. In curative resection cases, the longest survival time was 42 months; and in cases of non-curative resection, 26 months. Most of the nonresected patients died within 6 months with an operative mortality of 16.6 per cent. This report reinforces the difficulty in diagnosis and the poor prognosis for patients with primary carcinoma of the gallbladder. However, ultrasonography seems to be the best tool at present for detecting early cancer, especially cancer of the polypoid type. We hold the view that more radical approaches for relatively early cancer will enhance the operative results. PMID- 4037552 TI - Subclavian catheter changes every third day in high risk patients. AB - The subclavian catheter is commonly used in burn and trauma patients but remains a significant source of bacterial invasion in this group of seriously compromised individuals. The authors arbitrarily decided to change the catheter routinely every 3 days in consecutive patients to evaluate whether early detection of colonization and lowering of the infection rate was possible with this technique. At the time of change, catheter tips and central venous blood samples were sent for culture. Twenty-four venous blood samples were sent for culture. Twenty-four patients were studied in whom a total of 143 catheter changes over a wire introducer were performed. There were 20 men and four women with an average age of 34.5 years. Twenty patients with burns (average 48% body surface area involved), two patients with abdominal gunshot wounds, and two patients with complicated blunt trauma were studied. Five patients (three burns, two trauma) died, four because of sepsis, one of respiratory failure. Forty of the 143 catheter tips yielded positive cultures; however, 26 of these were not associated with overt sepsis. This 28 per cent incidence of positive catheter cultures was significantly less than the 47 per cent incidence reported previously in an identical patient population in whom the catheter was changed and cultured on clinical suspicion of sepsis (P value less than 0.001). There were 38 clinical episodes of sepsis, but the catheter could be implicated as the source in only five of these. Pseudomonas was the most common organism isolated from all sources. The authors conclude from this study that the incidence of positive catheters is significant in this high-risk group, but is decreased when the routine change protocol is implemented.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4037553 TI - The relationship between hepatic and cardiac function during hemorrhagic shocks in dogs. AB - The standard Wiggers' method was used to induce hemorrhagic shock in 13 anesthetized dogs by bleeding to a mean arterial pressure (MAP) of 50 mm Hg for 2 hours and then to 30 mm Hg for 1 hour, followed by reinfusion of the shed blood. The experimental protocol was designed to determine and relate hepatic function to cardiac function during hemorrhagic shock. Cardiac function parameters were recorded throughout the experiment on a multichannel polyoscillograph monitor, while liver function tests were done by using an automatic analyzer. Indices for cardiac performance, that is, left ventricular pressure (LVP), max dp/dt of LVP, left ventricular stroke work (LVSW), and right ventricular stroke work (RVSW) were all shown to be severely depressed at terminal stage. Transaminases (SGOT and SGPT) and lactate dehydrogenase (LDH), both being hepatic rich intracellular enzymes were very much elevated at terminal stage. This suggested that hepatic cell injury occurs in hemorrhagic shock as these enzymes seem to be leaking from damaged cells into bloodstream. Hepatic cell damage was confirmed to be present as the LDH isoenzyme electrophoresis showed a high frequency of liver fraction peak 5. Centrolobular hepatic necrosis was revealed by light microscopy. Cardiac function deterioration in hemorrhagic shock aggravates hepatic dysfunction. PMID- 4037554 TI - Management of aortoesophageal fistula. A case report. AB - A case of aortoesophageal fistula, secondary to a false aneurysm of the thoracic aorta is presented. Esophagoscopy and aortography are high-yield diagnostic procedures. The Sengstaken-Blakemore tube provides a satisfactory temporizing measure. Definitive repair should include aortic replacement with a Dacron graft through clean tissue planes. PMID- 4037555 TI - Weekly pulse methotrexate in rheumatoid arthritis. Clinical and immunologic effects in a randomized, double-blind study. AB - Twelve patients with refractory rheumatoid arthritis were treated with weekly pulse methotrexate in a double-blind, placebo-controlled, crossover study. After 13 weeks of therapy, patients receiving methotrexate showed greater improvement, judged by degree of joint swelling and tenderness, duration of morning stiffness, and subjective assessments of clinical condition, compared to those receiving placebo (p less than or equal to 0.002). This improvement was associated with a decrease in sedimentation rate and decreases in levels of IgG, IgM, and IgA; no changes were seen in serum rheumatoid factor titer or complement protein levels. Proportions of mononuclear cell subsets that were abnormal before treatment (decreased percentage of total T cells, increased percentage of monocytes) improved toward normal after therapy with methotrexate. However, no changes were seen in elevated pretreatment Leu-3/Leu-2 ratios, in in-vitro proliferative responses of lymphocytes to mitogens, or in immunoglobulin secretory responses to pokeweed mitogen. Weekly pulse methotrexate is effective in the short-term treatment of refractory rheumatoid arthritis. Little evidence for cellular immune suppression was associated with this clinical benefit. PMID- 4037556 TI - Pulmonic valve insufficiency: a common cause of transient diastolic murmurs in renal failure. AB - To study the transient diastolic murmur associated with renal failure, we used Doppler echocardiography to characterize flow across the semilunar valves in 10 patients on chronic hemodialysis with a diastolic murmur (group A), 26 patients on chronic hemodialysis without murmurs (group B), and 15 healthy persons (group C). Nine patients in group A had pulmonic valve insufficiency that encompassed 77 +/- 21% (SD) of diastole with peak regurgitant flow velocities of 1.7 +/- 0.3 m/s. Doppler-calculated mean pulmonary artery pressure in 8 of them was 43 +/- 7 mm Hg before dialysis and 20 +/- 12 mm Hg afterward (p less than 0.001). Dialysis reduced the duration of pulmonic insufficiency to 10 +/- 16% of diastole and lowered peak regurgitant flow velocities to 0.2 +/- 0.2 m/s (p less than 0.001 for each). Three patients in group B had aortic valve insufficiency and 3 had pulmonic valve insufficiency like that in group A. Three persons in group C had mild pulmonic valve insufficiency. Thus, transient diastolic murmurs associated with pulmonic valve insufficiency are not uncommon in patients with renal failure; they are related to fluid overload, are diminished by extracellular fluid removal, and reflect correctable pulmonary hypertension. PMID- 4037557 TI - Estimation of true calcium absorption. AB - Measurements of true calcium absorption fraction in women were evaluated to see how closely calculations based on a single measurement of serum specific activity after administration of an oral calcium tracer might approximate the absorption value derived from the full, double-isotope absorption procedure. True absorption, body size, and miscible pool turnover could together explain better than 93% of the variance in serum calcium specific activity values 5 hours after a tracer-labeled test meal. Because measurement of pool turnover is not available routinely, it was dropped from the model, and a predictor equation was developed that allowed estimation of true absorption from the 5-hour serum specific activity value, height, and weight. These variables explained 90.8% of the variance in the 5-hour values and gave estimates of true absorption with a 95% confidence interval of +/- 0.055. This small range of uncertainty makes the procedure useful in estimating absorption efficiency for calcium therapy in routine clinical practice. PMID- 4037558 TI - Thrombolytic therapy for inferior vena cava thrombosis in paroxysmal nocturnal hemoglobinuria. AB - Two patients with paroxysmal nocturnal hemoglobinuria had increasing abdominal girth and ascites. The Budd-Chiari syndrome or inferior vena cava thrombosis was shown by angiography. After thrombolytic therapy, both patients improved, and thrombolysis was shown by radiography. Neither patient had induction of hemolysis secondary to these agents. These studies suggest that both streptokinase and urokinase are safe and effective in the treatment of intra-abdominal venous thromboses associated with paroxysmal nocturnal hemoglobinuria. PMID- 4037559 TI - Information needs in office practice: are they being met? AB - We studied the self-reported information needs of 47 physicians during a half day of typical office practice. The physicians raised 269 questions about patient management. Questions related to all medical specialties and were highly specific to the individual patient's problem. Subspecialists most frequently asked questions related to other subspecialties. Only 30% of physicians' information needs were met during the patient visit, usually by another physician or other health professional. Reasons print sources were not used included the age of textbooks in the office, poor organization of journal articles, inadequate indexing of books and drug information sources, lack of knowledge of an appropriate source, and the time required to find the desired information. Better methods are needed to provide answers to questions that arise in office practice. PMID- 4037561 TI - An introduction to medical phenomenology: I can't hear you while I'm listening. AB - A great gulf exists between the way we think about disease as physicians and the way we experience it as people. Much of this separation derives directly from our basic assumptions about what illness is. Our medical world view is rooted in an anatomicopathologic view of disease that precludes a rigorous understanding of the experience of illness. What we need to remedy this problem is not just the admonition to remember that our patients are people, but a radical restructuring of what we take disease to be. The philosophic discipline of phenomenology is used to present a vision of disease that begins with an understanding of illness as it is lived. "Nonmedical" descriptions of illness show how we can reorient our thinking to encompass both our traditional paradigm and one that takes human experience as seriously as it takes anatomy. PMID- 4037560 TI - Consultation and referral between physicians in new medical practice environments. AB - The traditional exchange of medical expertise between physicians for patient benefit has been accomplished by referral. Physicians have traditionally decided when and to whom to refer patients. Health care "systems" now dominate medical practice, and their formats can alter spontaneous collegial interaction in referral. Institutional programs now pursue patient referrals as part of a marketing strategy to attract new patients who then become attached to the institution, rather than to a physician. Referral behavior can affect a physician's personal income in prepaid insurance programs where referrals are discouraged. The referring physician may bear legal liability for actions of the consultant. New practice arrangements and affiliations may place physicians in financial conflict-of-interest situations, challenge ethical commitments, and add new moral responsibility. PMID- 4037563 TI - Consultation and referral in new medical-practice environments: a gloomy outlook? PMID- 4037562 TI - Methotrexate treatment of rheumatoid arthritis. PMID- 4037564 TI - Lithotripsy. Health and Public Policy Committee, American College of Physicians. PMID- 4037565 TI - Ranitidine and hepatitis. PMID- 4037567 TI - Venous access ports. PMID- 4037566 TI - Sclerosing cholangitis. PMID- 4037569 TI - Sjogren's syndrome. PMID- 4037568 TI - Erythromelalgia without arteriolar changes. PMID- 4037571 TI - Preventive medicine and residency training. PMID- 4037570 TI - Mastocytosis and the hyperimmunoglobulin E syndrome. PMID- 4037572 TI - Psyllium hypersensitivity, nurses, and geriatric units. PMID- 4037573 TI - Intravenous amrinone. PMID- 4037574 TI - Immune thrombocytopenia in narcotics addicts. PMID- 4037575 TI - Incision and drainage of soft-tissue abscesses and bacteremia. PMID- 4037577 TI - Thyroxine bioequivalency. PMID- 4037576 TI - Gentamicin and hypokalemia. PMID- 4037578 TI - [Anatomical distribution of colorectal carcinomas in relation to age and sex. Our cases]. PMID- 4037579 TI - [Massive resections of the small intestine: methods and possibility of functional compensation]. PMID- 4037580 TI - [Stress ulcers. Clinical study of patients recovering in an intensive care center]. PMID- 4037582 TI - [Long-term results of subcutaneous bypass in aorto-iliac obstruction]. PMID- 4037581 TI - [A case of aneurysm of the splenic artery associated with a gastric neoplasm]. PMID- 4037583 TI - [Experimental study of anatomical or functional exclusion of the small intestine in swine]. PMID- 4037584 TI - [A new quantitative approach to cutaneous aging]. PMID- 4037585 TI - [Course of gonococcal arthritis: a retrospective study of 42 cases]. AB - The authors report a retrospective study of the evolution os gonococcal arthritis after antibiotic therapy. The prognosis i-good but the speed of recovery depends on early treatment. Post-septic arthritis is common (13/42) and requires local treatment. The diagnosis of post-infective and/or reactive gonococcal arthritis is discussed. PMID- 4037586 TI - [Pneumopathies caused by hypersensitivity to amiodarone and associated nephropathies. Study by alveolar lavage]. AB - Four cases of amiodarone-induced restrictive, hypoxaemic lung disease are described. The cumulative dosages of amiodarone were relatively low (30 to 100 g). Alveolar lavage studies showed a lymphocytosis and study of the lymphocytic sub-populations showed an increase in the OKT8 group, and an inversion of the OKT4/OKT8 ratio. The outcome was favourable on withdrawal of amiodarone and steroid therapy. The immunological origin of this form of lung disease was confirmed. Two patients had renal failure; in the first case, hypercalcaemia, hyperphosphoremia and renal calcification were observed. The second patient had endo- and extracapillary glomerulonephritis with C3 deposits and circulating immune complexes. Renal failure regressed in both cases on withdrawal of amiodarone and with steroid therapy. PMID- 4037587 TI - [Toxicity of Glucantime. A case]. AB - N-methylglucamine antimoniate (Glucantime) is used to treat visceral leishmaniasis but may give rise to serious and sometimes lethal complications: cardiac, hepatic, renal and haematological disease. These may be prevented by respecting the maximal suggested dosage of 6 cg/kg/day, regular clinical checks of pulse, blood pressure and temperature, biological follow-up of serum creatinin, transaminases and routine electrocardiography. PMID- 4037588 TI - [Anatomo-clinical conference. Hopital de la Pitie-Salpetriere. Case no. 3--1985. Anemia of recent onset in a 72-year-old woman]. PMID- 4037589 TI - [A case of spinal cord sarcoidosis]. PMID- 4037590 TI - [Blood hypereosinophilia with eosinophilic polyserositis and retroperitoneal fibrosis]. PMID- 4037591 TI - [Wegener's disease of urologic and neurologic onset]. PMID- 4037592 TI - [Alternative treatment for gastric stress ulcers: cimetidine or ranitidine?]. PMID- 4037593 TI - [Prolegomena to a new stage in psychiatry]. PMID- 4037594 TI - [Evaluation of anxiety and depression among patients hospitalized on an internal medicine service]. PMID- 4037595 TI - [Cases of despair in a sectoral psychiatric practice]. PMID- 4037596 TI - [Apropos of diagnostic difficulties in organic brain syndromes]. PMID- 4037597 TI - A revisit: ocular hypertension, glaucoma suspect, preglaucoma, or glaucoma? PMID- 4037598 TI - Visual prognosis in pituitary tumors. AB - In a study of 15 patients with pituitary adenoma, preoperative and postoperative evaluation of peripapillary nerve fibers by red-free fundus examination showed that a good correlation exists between preoperative loss of peripapillary nerve fibers and the final visual outcome. PMID- 4037599 TI - Optic disk findings in hypervitaminosis A. AB - Three cases of papilledema secondary to chronic excessive vitamin A intake are presented, and the optic disk changes are documented with intravenous fluorescein angiography. Two of the three patients reported in this study were symptomatic with blurred vision and systemic complaints. The symptoms of blurred vision and systemic complaints disappeared within one week, and papilledema resolved over several months after discontinuance of vitamin A. The fluorescein angiographic changes observed in the optic disk of patients with hypervitaminosis A are similar to those associated with other known causes of papilledema. Since vitamin A is a nonprescription drug, and its indiscriminate use is potentially great, any history of vitamin ingestion should be elicited during the evaluation of papilledema. PMID- 4037600 TI - Biomicroscopic study of the vitreous in eyes with macular pucker after retinal detachment surgery. AB - The posterior vitreous condition of 43 eyes with macular pucker following retinal detachment surgery was studied using the El Bayadi-Kajiura preset lens mounted on a slit lamp. The posterior vitreous was found to be attached in one eye (2%), completely detached in 29 eyes (68%), and partially detached with residual vitreoretinal adhesion to the macular area in 13 eyes (30%). Macular pucker with partial posterior vitreous detachment was significantly more frequent (P less than .05) in eyes with refractive errors of -4 diopters or less. That condition was also accompanied by a higher incidence of dye leakage in the macular area by fluorescein angiography, a shorter time lapse between retinal detachment surgery and development of macular pucker, and a worse visual outcome than was found in eyes with complete posterior vitreous detachment. PMID- 4037601 TI - A mimic of the "exact diagnostic sign" of Foster Kennedy. AB - We observed a patient with bilateral nonarteritic ischemic optic neuropathy presenting with gradual loss of vision in the right eye and initially asymptomatic disk swelling in the left. This atypical picture may create diagnostic difficulty, since sudden visual loss, the major distinguishing feature between Foster Kennedy's original syndrome and "pseudo-Foster Kennedy syndrome" of ischemic optic neuropathy, is lacking. PMID- 4037602 TI - Zinc and copper metabolism in patients with senile macular degeneration. AB - Abnormal zinc and copper metabolism has been described in some retinal disorders affecting the retinal pigment epithelium. Anatomic and functional studies in patients with senile macular degeneration show changes in this retinal layer. We examined the blood and urine of two groups of patients, one consisting of patients with senile macular degeneration and the other a control group, for zinc and copper in serum and urine. In the former group we found elevated values of serum zinc and serum copper that were highly significant when compared with the control group. The significance of these findings and their connection to the retinal pigment epithelium is discussed. PMID- 4037603 TI - Reversible monocular cataract simulating amaurosis fugax. AB - In a patient having brittle, juvenile-onset diabetes, transient monocular visual loss occurred repeatedly whenever there were wide fluctuations in serum glucose. Amaurosis fugax was suspected. The visual loss differed, however, in that it persisted over a period of hours to several days. Direct observation eventually revealed that the relatively sudden change in vision of one eye was associated with opacification of the lens and was not accompanied by an afferent pupillary defect. Presumably, a hyperosmotic gradient had developed with the accumulation of glucose and sorbitol within the lens. Water was drawn inward, altering the composition of the lens fibers and thereby lowering the refractive index, forming a reversible cataract. Hypoglycemia is also hypothesized to have played a role in the formation of a higher osmotic gradient. The unilaterality of the cataract is attributed to variation in the permeability of asymmetric posterior subcapsular cataracts. PMID- 4037604 TI - Prescribing spectacles for anophthalmic patients. AB - Clinical situations exist where socket reconstruction after enucleation is incomplete and additional surgery is contraindicated. The resultant cosmetic disfigurement may have a profound effect on the patient. An illustrative case is presented. Available methods of anophthalmic camouflage are reviewed, and a relatively inexpensive technique is described that relies on optical cosmesis to give the patient a natural and symmetric appearance. PMID- 4037605 TI - Surgical treatment of dislocated iris-plane intraocular lenses. AB - This report describes a patient with a Binkhorst four-loop intraocular lens dislocated in the vitreous. The implant was repositioned by means of a combination of the Barraquer-Chowdhury needle-fixation method with a McCannel suture. The pupil was maximally dilated, and the patient was placed in the prone position. When the implant drifted into the anterior chamber, it was anchored with a 25-gauge spinal needle through the limbus. It was then refixated to the iris with a 10-0 prolene suture. PMID- 4037606 TI - Minnesota Multiphasic Personality Inventory: comparison of patients accepting and rejecting myopia surgery. AB - The Minnesota Multiphasic Personality Inventory (MMPI) was administered to 36 consecutive patients presenting to one surgeon as candidates for myopia surgery. Twenty-one patients proceeded to surgery, and 15 did not. The patients in this series were mature, nonaggressive persons whose basic and clinical MMPI scale values were generally within normal limits. No significant differences were found between the group that underwent surgery and the group that did not. In the group that underwent surgery, no personality characteristics were found to be associated with either a good or a poor surgical result. To our knowledge, this is the first report of the use of the MMPI to objectively evaluate personality characteristics of candidates for myopia surgery. PMID- 4037607 TI - [Evaluation of public health services by 805 women who had delivered in a Brianza hospital]. PMID- 4037608 TI - [Experiences at the hospital on the occasion of childbirth. Analysis of subjective experiences of 846 puerperants in a hospital in Northwestern Lombardy]. PMID- 4037609 TI - [Diagnostic reliability of the endometrial swab in the detection of preneoplastic and neoplastic lesions of the endometrium]. PMID- 4037610 TI - [Epidermoid cysts of the ovary]. PMID- 4037611 TI - [Obstetric-gynecologic day hospital: analgesia for voluntary interruption of pregnancy]. PMID- 4037612 TI - [Intra-arterial chemotherapy of ORL tumors. 10 years' experience in the Antoine Lacassagne Center]. AB - One hundred and two patients with malpighian epithelioma of ORL origin were treated with intra-arterial chemotherapy (IAC) as initial therapy, followed by either surgery, radiotherapy or a combination of the two. Regression in tumor size of more than 50% was noted in 46% of cases, the introduction of cisplatin into the multiple system chemotherapy providing a response in 71% of the 42 patients treated in this way. A response to induction IAC is a factor of good prognosis as shown by the improvement in level of local and regional extensions and the probability rate of survival in responders. Technical and methodologic progress has made IAC a simple and effective procedure, and its place in the treatment of epitheliomas of head and neck should be established more precisely. PMID- 4037613 TI - [Retrospective study of the treatment of piriform sinus cancers. Apropos of 97 cases]. AB - Results of a retrospective analysis of case-reports of 97 patients treated for piriform sinus cancer showed a high frequency of large tumors and adenopathies providing an explanation for the very poor prognosis of these cancers. Therapy of choice for T1-T2 tumors is still radiotherapy. However, recently obtained results and data from the literature demonstrate the increased benefits of partial surgery with monoblock curettage followed by radiotherapy in cases with an ulcerous tumor, a mobile larynx and adenopathy of 3 cm or more. For T3-T4 cases the best treatment is by total pharyngolaryngectomy and postoperative radiotherapy. PMID- 4037614 TI - [Cervical adenopathies in relation to AIDS. Course of histological aspects. Diagnostic and prognostic value]. AB - Histopathologic appearances of lymph nodes during acquired immune deficiency syndrome (AIDS) and related conditions are analyzed, with emphasis on the diagnostic and prognostic value of cervical gland biopsy at the lymphadenopathic stage. Details are given of the characteristics of the follicular hyperplasia of the lymph nodes (type I), which appears to be the initial lesion and is possibly regressive, and emphasis placed on the poor prognostic significance of the hyperplasia simulating a Castleman syndrome and of the forms simulating an angioimmunoblastic lymphadenopathy (type II). Findings suggest that the appearance, in a still hyperplastic lymph nodes, of foci of pseudo angioimmunoblastic homogenization, of fibroedema with lymphoid depletion or conjunctival vascular proliferation may be the initial sign of a course towards the glandular atrophy (type III) or Kaposi's sarcoma which are the attribute of confirmed AIDS. PMID- 4037615 TI - [Translation esophageal flap in the repair of traumatic stenosis of the hypopharynx]. AB - A surgical technique is proposed which makes use of a cervical esophageal flap to repair a hypopharyngeal stenosis from traumatic intubation. The technique is also applicable for identical stenosis of caustic or traumatic origin, other procedures described in the literature being suitable only for more extensive or more limited lesions. This simply performed technique provides important mucosal gains in the piriform sinus region and a satisfactory hypopharyngeal line. PMID- 4037617 TI - [Total "pharyngoplastia vera" with the colon in caustic pharyngo-laryngeal stenoses]. AB - An original procedure for pharyngeal reconstruction with colon in pharyngolaryngeal stenosis due to chemical burns has been named "pharyngoplasty vera" by the authors, since the 3 walls of the pharynx are reconstituted by lining it with visceral material. This is in contradiction with previously used techniques in which the graft caps the pharyngostomy produced by resection of scar tissue (pharyngovisceral anastomosis). The procedure generally respects the principles of conventional cutaneous pharyngoplasty--similar approach, extirpation of scar tissue, epiglotto plasty, conservation of constrictor muscles and above all, solid attachment of visceral material to the latter, and finally suture of the colon at the base of tongue and closure of pharynx. The method was used in a patient who regained deglutition rapidly, but the insufficient glottic space did not allow reopening of the canal. PMID- 4037616 TI - [Partial pharyngo-laryngectomy with subtotal esophagectomy and 1-stage coloplasty]. AB - A patient with cancer of both the hypopharynx and esophagus was treated by partial pharyngolaryngectomy, subtotal esophagectomy and a reconstructive one stage coloplasty. Surgical and carcinologic problems raised by this technique are discussed. PMID- 4037618 TI - [Myringoplasty in children]. AB - An anatomical success rate of 81% was obtained in 150 children 2 to 15 years of age operated upon by myringoplasty in the hospital Bretonneau, Paris between 1977 and 1984. Results were unrelated to age the season or the condition of the mucosa. Adverse factors were a previous history of a transtympanic aerator, a velar cleft or bilateral perforations. Mean functional gain after 1 year was 14 dB. It was not related to age or the technique used. PMID- 4037619 TI - [Congenital esophagotracheal fistulas without esophageal atresia in children]. AB - Ten cases are reported of children presenting isolated, congenital esophagotracheal fistulae without esophageal atresia, or "H-type-fistula" of Anglo-Saxon authors. The malformation is rare, of difficult diagnosis and often associated with other malformations. Respiratory symptomatology is sometimes dramatic, but diagnosis is based on data from radiologic imaging of the esophagus and from esophageal and tracheobronchial endoscopy. Treatment is surgical by a cervicotomy approach due to the almost constant high localization of the lesion. PMID- 4037620 TI - [Audition and information theory: application to cochlear analysis]. AB - Application of the general theory of information and of communication to auditory function enables the internal ear to be assimilated to a digital-analog converter capable of coding the continuous acoustic signal into discontinuous, impulsional type nervous signals. In this model, the ear selects spatio temporal samples of membranous acoustic forms, discrimination of intensity devolving upon the external ciliated system and that of the height upon the internal ciliated system. It allows simple correlation of apparently paradoxical psycho-acoustic phenomena with objective acoustic or histopathological data. PMID- 4037621 TI - [Deafness and autoimmunity]. AB - The etiology of a perception deafness cannot be determined in most cases. The autoimmune origin of some of them appears now to be increasingly possible, particularly when they form part of a disease affecting multiple systems. Three cases of this type are presented in an attempt, by analogy, to define the pathogenicity and criteria of the isolated "dysimmune" audiovestibular manifestations. PMID- 4037622 TI - [Changes in IgA levels in nasal mucus after upper respiratory tract diseases in infants treated with carbocysteine]. AB - The authors have studied IgA level in nasal mucus of children, either not treated controls, or treated with carbocysteine. All had common rhinobronchial diseases. They have noted a significant increase in IgA level in the treated group, from the 7th day. PMID- 4037623 TI - [A case of primary melanoma of the nasal fossae]. AB - Primary malignant melanoma of upper respiratory and digestive pathways are rare rand reputedly more serious than those occurring on the skin. Treatment is usually by surgery with or without combined radiotherapy and/or chemotherapy. A case of primary malignant melanoma of the nasal fossae is reported and diagnostic and therapeutic difficulties discussed. PMID- 4037624 TI - [Traumatic deafness with a surprise. Apropos of a case]. PMID- 4037625 TI - [Decompression of the facial nerve for frigorific paralysis 25 years previously, with clinical and electrical recovery of the motor function of the nerve]. PMID- 4037626 TI - [Toton, a new total prosthesis for replacement of the ossicle chain]. AB - After 4 years of use a new total prosthesis is proposed for replacement of the auditory ossicles, that is perfectly biocompatible since it is composed partly of the fresh autologous cartilage, which will be in contact with the drum and partly of teflon, which will be in contact with the foot of stapes. Results of a study in 44 patients, with follow up of more than 4 years in some cases, have shown: recovery of from 50 to 91% of audition in 61% and from 30 to 49% in 25% of cases, and lack of recovery in 13%. The Toton should resolve the problem of biocompatibility, a very controversial subject, and provide a solution to functional rehabilitation of empty cavities. PMID- 4037627 TI - [Early congenital syphilis: apropos of 5 cases]. AB - Congenital syphilis has in large part disappeared in countries where antiveneral legislations and preventive measures are well developed. In France, although there is no declaration of congenital syphilis between 1971 and 1983 in the official statistics of the Paris region, congenital syphilis is nevertheless mentioned as sporadic cases. The authors report here five cases of precocious congenital syphilis collected from august 1981 to december 1982 by a department of antiveneral consultations in the Paris region. PMID- 4037628 TI - [Primary tuberculous chancre of the penis with cutaneous verrucous dissemination]. PMID- 4037630 TI - Parathyroid carcinoma: pointers to successful management. AB - Five patients with parathyroid carcinoma are reported. In the first case the clinical and histological features of malignancy at initial surgery were not recognised and recurrence of the tumour occurred within two years. Referring to previously published series this sequence appeared to be typical and underlined the likely reasons for the poor prognosis of this rare tumour. A review of the diagnostic criteria to improve early diagnosis was undertaken and a treatment protocol drawn up. It was based on a more radical surgical extirpation to include the tumour bed together with postoperative radiotherapy. Four further cases have subsequently been identified, treated according to the protocol and at 16 to 49 months' follow up, show no sign of recurrence and have a normal serum calcium. PMID- 4037629 TI - A quantitative assessment of results with the Angelchik prosthesis. AB - The Angelchik antireflux prosthesis was assessed in 15 unpromising patients, 12 of whom had peptic strictures of the oesophagus. Radiological techniques were used to show the effect of the device on gastro-oesophageal reflux, and on the bore and length of strictures. Twelve months later (range 6-24) most patients were well satisfied with the operation, and all considered it had been worthwhile; there was radiological evidence of reduction in reflux and remission of strictures. The device never surrounded the oesophageal sphincter; in all but 1 case it encircled a tube of stomach. PMID- 4037631 TI - Povidone-iodine bowel irrigation before resection of colorectal carcinoma. AB - Preoperative mechanical bowel preparation, peroperative topical antiseptic measures, and postoperative antibiotic therapy have all been shown to reduce infection after colorectal surgery. We report the results of a randomised trial of preoperative irrigation with a 10% aqueous solution of povidone-iodine (Betadine) versus water in patients undergoing major resection for large bowel carcinoma. All patients had mechanical bowel preparation, preoperative topical povidone-iodine and per and postoperative antibiotics. Of 22 study patients only one (4.6%) developed abdominal wound infection, whereas in 23 controls nine (39.1%) did so (P less than 0.01). In three of the study patients cultures of swabs taken at operation from the transected bowel ends showed no bacterial growth. Arguably the bacterial population would have been markedly reduced in other patients. These results suggest that povidone-iodine irrigation before large bowel resection reduces wound sepsis. PMID- 4037632 TI - Relief of dysphagia in motor neurone disease with cricopharyngeal myotomy. AB - The results of cricopharyngeal myotomy in 31 patients with dysphagia caused by motor neurone disease are reported. Two had an excellent result, 8 a good result, 11 moderate relief of dysphagia while 4 did not benefit at all. There were 6 postoperative deaths. It is suggested that the operation is of benefit to the majority of patients with motor neurone disease but should be performed early in the course of the disease in order to reduce mortality and morbidity. PMID- 4037634 TI - An anatomical curiosity. PMID- 4037633 TI - The association between lowest palpable pulse and wound healing in below knee amputations. AB - A retrospective study of 191 patients undergoing 203 Burgess type below knee amputations for end-stage peripheral vascular disease showed that the only clinical feature which associated significantly with wound healing was the lowest palpable pulse. The pulse level was noted preoperatively and was compared with the healing rates in the amputation stumps. When the femoral pulse was absent, 79% of below knee amputations failed. When the femoral pulse was palpable, only 29% wound breakdown occurred. When the popliteal or more distal pulses were palpable, only 10% failure was recorded. PMID- 4037635 TI - The behaviour of presternal scars in a fair-skinned population. AB - The incidence of keloid and hypertrophic change and of scar stretching in the presternal region were studied in a fair-skinned population following open heart surgery through a median sternotomy incision. No patient in this study developed keloid change although scar hypertrophy and stretching were frequent. These changes were unrelated to the material used in subcuticular suture of the skin in a comparison of catgut, prolene and polyglycolic acid. Hitherto, unrecognised differences of scar maturation between different areas of the presternal skin were noted to be statistically significant. Scar hypertrophy is most likely in that part of the scar overlying the body of the sternum and particularly in the female. Scar stretching occurs most frequently in the lower third of the scar overlying the xiphisternum and extending onto the abdomen. PMID- 4037636 TI - Girth measurement is not a reliable investigation for the detection of intra abdominal fluid. AB - Routine measurement of abdominal girth after suspected trauma is still recommended as a predictor of intraperitoneal bleeding but there is little evidence to support its accuracy. Girth measurements were taken on 12 recumbent adult patients by independent observers and repeated after infusion of 550 ml aliquots of dialysate to a maximum of 2000 ml. Girth increase per 500 ml infusion varied from -0.46 cm to 2.1 cm (mean 0.84 +/- 0.65 SD) giving a range in excess of 2.5 cm. In some cases the girth decreased after a further 500 ml infusion. A change in patient position altered the girth at a constant volume by 1.32 cm (+/- 0.75 SD). Observer error was low at 0.33 cm (+/- 0.35 SD). These results preclude girth as a reliable clinical indicator of intraperitoneal haemorrhage. PMID- 4037637 TI - Simple mastectomy under local anaesthesia. AB - Nine patients with locally advanced carcinoma of the breast underwent simple mastectomy under regional anaesthesia (1% lignocaine and 1:100,000 adrenaline). Preoperative sedation was provided by oral lorazepam. There were no technical problems, evidence of lignocaine toxicity or excessive operative blood loss and no wounds became infected. PMID- 4037638 TI - Use of the Limberg flap to close breast wounds after partial mastectomy. AB - Early experience using a rhomboid flap to reconstruct the breast after partial mastectomy and axillary clearance of glands is encouraging. This operation has been used in 7 cases to reconstruct breasts after partial mastectomy and axillary clearance of glands and has given a good cosmetic result. PMID- 4037639 TI - Caecal volvulus: a method of management. AB - A case of caecal volvulus treated by derotation and ileostomy-in-situ is described. This operation is commended for caecal volvulus in cases where the intestine remains viable. PMID- 4037640 TI - Femoral herniae in children. AB - A series of 12 femoral herniae in children is presented. Nine were misdiagnosed, eight as inguinal hernia. Nine were reducible. The sex incidence, M:F was 7:5 and nine presented between the ages of 8 and 10 years. One presented as intestinal obstruction due to a Richter's hernia and two had had a previous ipsilateral inguinal hernia repaired. All but one were repaired by herniorrhaphy. PMID- 4037641 TI - Pulmonary implications of resuscitative manoeuvres. PMID- 4037642 TI - Caudal morphine for pain relief following anal surgery. AB - A prospective randomised trial was conducted to evaluate caudal morphine for pain relief following anal surgery. Thirty-three male patients were divided into two groups. Group I (17 patients) were given morphine 10 mg in saline 25 ml injected into the caudal epidural space at the end of surgery. Group II (16 patients) were given intramuscular morphine 10 mg on request in the postoperative period. Pain was assessed at 2, 6, 12 and 24 hours after surgery using the linear analogue of pain score. There was significant pain relief in Group I compared with Group II. There was no instance of respiratory depression in patients of either group. In Group I, five patients suffered urinary retention and three patients transient pruritus. PMID- 4037643 TI - The use of a microcomputer for inpatient audit in an orthopaedic department. AB - A microcomputer has been used to assist in the inpatient audit of an orthopaedic unit in a district general hospital. The aims were to provide a more detailed, accurate audit, more rapidly than previous manual methods had allowed. The clinical details of 609 patients treated over a 9-month period were fed into the computer and various statistical analyses performed. The results of the audit are presented. The extent to which our aims have been achieved is discussed together with the specific problems encountered with computer hardware, software and organisation of the system. PMID- 4037644 TI - Long-term venous access using a subcutaneous implantable drug delivery system. AB - To facilitate long-term venous access in patients receiving chemotherapy, a subcutaneous totally implantable system (Port-a-Cath, Phamacia) has been used in 14 patients. The method of implantation and the advantages over conventional central venous catheters are discussed. The expense of the system necessitates careful patient selection. PMID- 4037645 TI - Comparison of early and late closure of transverse loop colostomies. PMID- 4037646 TI - The efficacy of agents employed to prevent anastomotic recurrence in colorectal carcinoma. PMID- 4037647 TI - Inguinal hernia repair using local anaesthesia. PMID- 4037648 TI - Primary suture of the perineal wound using constant suction and irrigation, following rectal excision for inflammatory bowel disease. PMID- 4037649 TI - Treatment of oesophageal perforation by intubation. PMID- 4037650 TI - A system for long term perfusion of arterial cannulae. PMID- 4037651 TI - Silastic foam dressing: an appraisal. PMID- 4037652 TI - The importance of the lymphatic system. PMID- 4037653 TI - [Current role of Latarjet's operation in the treatment of recurrent luxations and anterior instabilities of the shoulder]. PMID- 4037654 TI - [Peroperative peritoneal lavage in peritonitis of appendicular origin in children. Apropos of 50 cases]. PMID- 4037655 TI - [Intentional temporary duodenostomy in gastroduodenal surgery. Apropos of 16 cases]. PMID- 4037656 TI - [Treatment of inguinal hernia without opening the peritoneum in ascitic cirrhosis]. PMID- 4037657 TI - [Mucinous cystadenoma of the pancreas: an entity not to be underrated. Review of the literature apropos of a case]. PMID- 4037658 TI - [Total gastroduodenal necrosis caused by acute postoperative pancreatitis. Temporary choledochostomy. Recovery]. PMID- 4037659 TI - [Pseudotumoral form of hepatic tuberculosis. Review of the recent literature. Apropos of a case]. PMID- 4037660 TI - [Congenital dilatation of the liver and common bile duct. Apropos of a case in an adult]. PMID- 4037661 TI - [Complicated esophagectomy. Therapeutic possibilities]. PMID- 4037662 TI - [A case of retroperitoneal tumor (leiomyosarcoma) simulating a kidney tumor]. PMID- 4037663 TI - Determination of aluminium in serum: findings of an external quality assessment scheme. AB - The analytical performance of laboratories participating in the serum aluminium programme of the Guildford Trace Element Quality Assessment Scheme has been evaluated. The considerable disparity between reported results was not attributable to the nature of the samples distributed, nor to the standard aluminium solutions used in different laboratories. All laboratories used electrothermal atomic absorption spectrometry but sample preparation procedures and temperature programmes varied enormously. While some laboratories performed better than others in the scheme, and the standard of analysis appears to be improving with time, no laboratory showed consistent acceptable performance. PMID- 4037664 TI - The determination of glucose and glycosylated haemoglobin in a non-diabetic Zimbabwean African population. AB - Reference intervals for plasma glucose and glycosylated haemoglobin A1 (HbA1) have been established in a Zimbabwean population aged 19-65 years. The subjects were a volunteer group of 777 people (440 male and 337 female). There was no significant difference in the glucose levels between men and women and the range was 2.58-5.62 mmol/L. There was, however, a significant difference in the HbA1 levels between men and women (P less than 0.001); the ranges found were: men, 4.86-9.78%; women, 4.30-8.22%. On comparison between HbA1 in the Zimbabwean population and published results a statistically significant difference was observed (P greater than 0.002). This study highlights the importance of determining reference intervals for each sex and ethnic group. PMID- 4037665 TI - High electroendosmotic agarose electrophoresis and nitrocellulose immobilisation for the detection of oligoclonal bands in unconcentrated cerebrospinal fluid. AB - A sensitive (1 microL of unconcentrated sample), specific (IgG Fc) and economical (10 p/test) method for the detection of oligoclonal bands in cerebrospinal fluid is presented. Using commonly available technology (agarose gel electrophoresis) and giving results within 6 h, the approach used here is a powerful tool in the investigation of immunoglobulin abnormalities in many biological fluids. PMID- 4037666 TI - Changes of methodology and their potential effects on data banks for drug effects on clinical laboratory tests. AB - Some of the implications of method changes on data banks-for the effects of drugs on clinical laboratory tests are discussed. Using data from Wellcome Clinical Chemistry Quality Control Programmes, separated by a period of ten years, significant changes of methodology used by participants are illustrated. These changes are related to a recognised listing of drug effects in clinical chemistry tests available in 1975. It is suggested that information from external quality assessment schemes is used periodically to review the relevance of data in relation to major changes of methodology. PMID- 4037667 TI - Dried blood spot test estimation of urea. AB - The analysis of urea in serum and whole blood samples dried onto filter paper has been investigated. In both cases the sample volume is not critical nor is the volume of sample applied to the filter paper if sample discs of consistent dimensions can be punched from the dried paper. The method must be calibrated by a serum-based material not an aqueous standard, presumably because of a matrix effect. A coefficient of variation of approximately 6% has been achieved over a wide range of urea concentration and the method has been shown to correlate well with a standard laboratory procedure. The technique has a particular application to neonatal capillary samples. PMID- 4037669 TI - Cytidine deaminase--a marker for pre-eclampsia? AB - Cytidine deaminase (cytidine aminohydrolase, EC 3.5.4.5) was measured in blood collected for routine antenatal monitoring from 590 unselected pregnant women. The enzyme measurements were made without prior knowledge of the clinical condition of the patients. Increased activity of cytidine deaminase was found in 42.9% of patients with severe pre-eclampsia, 9.1% of patients with mild pre eclampsia and in 8.6% of normal pregnancies. These results show a poor correlation of elevated cytidine deaminase activity with pre-eclampsia and a significant false positive elevation of the enzyme activity in normal pregnancies. PMID- 4037668 TI - Continuous-flow assay for urinary oxalate using immobilised oxalate oxidase. AB - A continuous-flow assay for measuring oxalate in urine is described. Covalently attached oxalate oxidase (EC 1.2.3.4) is used to oxidize the oxalate anion to carbon dioxide and hydrogen peroxide. The formed hydrogen peroxide is measured colorimetrically (A580) with an established reaction using horseradish peroxidase (EC 1.11.17), 3-methyl-2-benzothiazolinone hydrazone (MBTH) and 3 dimethylaminobenzoic acid (DMAB). Ascorbate interference is eliminated by treating the urine sample with sodium nitrite prior to assaying. The assay is accurate (mean recovery of added oxalate in spiked urine sample is 93 +/- 11%), sensitive (detection limit 1.0 mumol/L), reproducible (within-batch CV 3.5%; between-batch CV 5%) and relatively rapid (15 samples/h). This assay correlates well (R = 0.99) with another established enzymatic method (using oxalate decarboxylase). PMID- 4037670 TI - Changes in erythrocyte transketolase activity and the thiamine pyrophosphate effect during storage of blood. AB - Whole blood and washed erythrocytes from nutritionally normal and abnormal elderly patients were stored at room temperature, 4 degrees C and -20 degrees C for up to 14 days. In both groups, and under all storage conditions, the erythrocyte transketolase (ETK) activity and the thiamine pyrophosphate (TPP) effect decreased with time of storage. The ETK activity for specimens stored at 20 degrees C decreased significantly by day 14 (P less than 0.05). The TPP effect in specimens stored at -20 degrees C decreased significantly in the nutritionally abnormal group at 4 days (P less than 0.05) and in the nutritionally normal group by day 14 (P less than 0.05). These significant changes in ETK activity and TPP effect with storage can lead to misleading interpretation of thiamine nutritional status. PMID- 4037671 TI - Deming's regression analysis in method comparison studies. PMID- 4037672 TI - The value of CEA measurement in clinical practice. PMID- 4037673 TI - Frequency, multiplicity and repertoire of intestinal protozoa in healthy homosexual men and in patients with gastrointestinal symptoms. AB - Various conventional parasitological methods were used to study three faecal samples from 153 homosexual men and 119 patients with abdominal symptoms. In 59.5% of the homosexual men 198 protozoa were identified, and in 31.9% of the patients the number of protozoa was 51. Cryptosporidium and Giardia lamblia were more frequent in the patients, while various amoebae were more frequent in the homosexual men. The frequency, multiplicity and repertoire of intestinal protozoa in the homosexual men were very similar to those reported from other parts of the world, but quite different from those associated with gastrointestinal illness in the local general population. PMID- 4037674 TI - A prospective study of Chlamydia trachomatis in first trimester abortion. AB - Chlamydia trachomatis was isolated from 34 (17.9%) of 190 unselected women applying for first trimester abortion and from 27 (15.9%) of the 170 women who actually had the operation. C. trachomatis was more common among the younger women. Neisseria gonorrhoeae was isolated from 3 (1.6%) of 190 women. Culture positive patients and partners were given antibiotic treatment for 10 days, usually postoperatively. Early postoperative genital infection developed in 2 (7.4%) of the 27 chlamydia-positive and in 3 (2.0%) of the 143 chlamydia-negative women. There were no late infections. The antibiotic treatment significantly reduced the rate of postoperative pelvic inflammatory disease. At examination after 4-7 weeks all cultures were negative. Significantly more women with chlamydia-positive cultures were sero-positive preoperatively: with a microimmunofluorescence method, IgG titres greater than or equal to 1:160 were found in 74.1% of culture positive and in 47.6% of culture negative patients (p = 0.01). However, serological IgG screening does not identify individual high risk patients and so is of little clinical use in this context. We recommend preoperative screening for C. trachomatis in all women requesting an abortion and 10 days antibiotic treatment for all carriers. PMID- 4037675 TI - Biological false positives to serological tests for syphilis in herpes genitalis. AB - A survey was made of 17 patients (4 females and 13 males) with herpes genitalis who, during period 1971-84, developed biological false positive serological tests for syphilis. Of 121 patients with herpes genitalis diagnosed by herpes culture in 1982-84, 4.1% developed biologically false positive reaction. Duration of symptoms before biologically false positive reaction was 12 days. Duration of false positive reaction was on average 32 days. Eight had borderline reactions, 7 uneven positive titers and 2 serological patterns simulating secondary syphilis. PMID- 4037677 TI - Diabetes and diabetology in Singapore. PMID- 4037676 TI - Diagnosis of reflux esophagitis. With special reference to double contrast radiography. AB - The correlation between radiography, endoscopy, and histology in the diagnosis of reflux esophagitis, as well as the effect of glucagon on double contrast radiography was studied. The material consisted of 220 out-patients sent to the Oulu University Central Hospital for upper gastrointestinal endoscopy. 109 of these were shown to have reflux esophagitis at endoscopy, the other 111 formed a control group with normal esophageal mucosa. Radiologic examinations were performed after endoscopy on the same day by a radiologist, who knew neither the clinical history of the patients nor the findings at endoscopy. Using endoscopy as a reference, 56% (28/50) of the patients with grade E I reflux esophagitis (erythema, oedema) were diagnosed correctly by double contrast radiography. The corresponding figures concerning grade E II (erosions), grade E III (localized deformity, ulcer), and grade E IV (stricture) reflux esophagitis were 84% (41/49), 100% (4/4), and 100% (6/6). False positive findings were found in 4.5% (5/111). The sensitivity of double contrast radiography as compared to endoscopy in all grades was 73%, its specificity was 96%, and accuracy 84%. The corresponding figures, when only grades E II, E III, and E IV are considered, were 86%, 96%, and 92%. In double contrast radiography, signs sometimes visible in grade E I reflux esophagitis were thick mucosal folds and mucosal granularity. Reliable signs of grade E II reflux esophagitis were streaks and dots of barium against the mucosa either alone or together with thick mucosal folds and mucosal granularity. Specific signs of grade E III and E IV reflux esophagitis were- along with the above--localized deformities, ulcers, and strictures. A hiatus hernia or wide hiatus was detected radiologically in 2/3 of the reflux esophagitis patients, and in 1/3 of the controls. Histologic findings correlated poorly with both endoscopic and radiologic findings. Single contrast radiography was less sensitive than double contrast radiography in detection of superficial mucosal lesions. Glucagon had no advantagous effect on esophageal double contrast radiography. Its use, however, in connection with double contrast radiography of the stomach is unlikely to have any disadvantagous effect on the evaluation of the hiatus and gastroesophageal reflux. PMID- 4037678 TI - A comparative study of three methods of glycosylated haemoglobin measurements. AB - This report summarizes our experience with 3 methods of glycosylated haemoglobin (HbA1) determinations. Glycosylated haemoglobin levels were determined using microcolumn chromatography (Boehringer Mannheim), agar gel electrophoresis (Corning GlytracTM) and colorimetry. The HbA1 values for 40 normal controls using chromatography, electrophoresis and colorimetry were 7.31 +/- 0.67 (+/- 1 S.D.), 7.98 +/- 0.81 and 8.54 +/- 1.09% respectively. The intra-assay coefficients of variation were 3.3, 4.5 and 2.0% respectively. There were also good correlations among the 3 methods of HbA1 measurements: electrophoresis vs chromatography, r = 0.91 (p less than 0.001) and electrophoresis vs colorimetry, r = 0.84 (p less than 0.001). Similarly, all 3 methods correlated well with the fasting and mean grouped blood glucose values (p less than 0.001). The chromatographic method is precise and well suited for small sample analysis. The colorimetric method, although the least expensive is labour intensive, suitable only for large batch analysis and in situations where results are not required immediately. The electrophoresis method is also precise, the least labour intensive and well suited for small and large volume laboratories. This study showed that since all 3 methods demonstrated similar precision and good correlation with fasting and grouped blood glucose values, the method of choice will depend on the requirements and support facilities of the individual laboratories. PMID- 4037680 TI - The variation of glucose tolerance in a multi racial population. AB - The pattern of plasma and urine sugar changes after 50g glucose load in 1900 Malaysians (522 males and 1378 females) consisting predominantly of Malays, Chinese and Indians were studied. The data were analysed using Statistical Package for Social Sciences (SPSS). The results show bimodal distribution of 120 min. plasma sugar values in the age groups 21 years and above and trimodal distribution in most groups above 40 years. The mean 120 minutes plasma sugar cut off values for nondiabetics (ND), impaired glucose tolerance (IGT), and diabetics (DM) of 8.4 and 11.1 mmol/l respectively were close to the values recommended by the National Diabetic Data Group (NDDG). Fifty two percent of all subjects showed peaked plasma sugar values at 60 minutes (14% of them had IGT, 12% DM), 25% peaked at 30 minutes (98% of them were ND). The rest showed peaked values at 90 minutes (17%), 120 minutes (4%) and 150 minutes (2%) and from this group forty two percent were DM and 23% had IGT. Reliance on urine sugar qualitative tests could misclassify 7.3% of subjects (predominantly elderly females) with hyperglycaemia of greater than 11 mmol/l. This study shows that in the 50 g glucose tolerance test, the NDDG criteria for ND, IGT, DM is still applicable to the Malaysian population. The sampling time could be reduced to four points at 0, 60, 90, and 120 minutes. Blood analysis is the preferred method for the diagnosis of hyperglycaemia in elderly females. PMID- 4037679 TI - Fast fraction haemoglobin (HbA1) in the assessment of diabetes control. AB - The degree of control of 132 diabetic patients was assessed using historical data, urine glucose and blood glucose measurements. These were then related to HbA1, taken as the final arbiter of glycaemic control. Symptoms of hyperglycaemia and glycosuria were found to be not sensitive or specific indices of control, though symptomatic glycosuric patients tended to have higher HbA1. Fasting blood glucose correlated modestly with HbA1 (r = 0.60, p less than 0.001) but if used alone to determine degree of control, 21% and 9% of patients could be expected to be over or under assessed respectively. The assessment value of timed post breakfast blood glucose applied only to 120 and 150 minutes post-breakfast blood glucose as they correlated well with HbA1 (r = 0.73, p less than 0.001 and r = 0.96, p less than 0.001 respectively). Clinically impression of degree of control based on a combination of historical data, urine glucose and blood glucose led to "undertreatment" in 41% and "overtreatment" in 27% of patients. The complementary value of a knowledge of HbA1 was thus highlighted. PMID- 4037681 TI - Epidemiology of diabetes mellitus in Singapore: comparison with other ASEAN countries. AB - Singapore is a tropical island city-state with a population of 2.4178 million consisting of Chinese (76.7%), Malays (14.7%), Indians (6.4%) and other races (2.2%). A diabetic survey of the adult population, aged 15 years and above, carried out in 1975, shows that the prevalence of diabetes is 1.99%; it is higher in males (2.36%) than in females (1.64%). It occurs mainly in the age group 40 years and above (5.08%) and is uncommon in the age group 15-39 years (0.40%). In males, the highest prevalence of diabetes (7.0%) is in the age group 45-49 years while in females the highest prevalence (7.2%) is in the age group 55-59 years. 43.3% of the diabetics are of normal weight while 44.3% are overweight and 12.4% are underweight. 59.6% of the diabetics are newly diagnosed while 40.4% are known diabetics; 64.3% of the newly diagnosed diabetics have no symptoms. The prevalence of diabetes among the Indians (6.07%) is significantly higher than that in Malays (2.43%) and Chinese (1.55%). Indian diabetics have a slightly higher positive family history of diabetes (12.7%) than Malays (10.9%) and Chinese (6.5%). Obesity is commoner in Malay diabetics (64.7%) than in Chinese (41.6%) and Indians (35.7%). The possible factors leading to the significantly higher prevalence of diabetes among the Indians compared to the other ethnic groups in Singapore are discussed. It is suggested that the Indian gene is susceptible to diabetes (diabetic genotype) and increased food consumption, altered lifestyle and greater obesity leads to the expression of diabetes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4037682 TI - Home blood glucose monitoring, glycaemic control and diabetic complications. AB - The aim of this study was to evaluate the effect of home blood glucose monitoring on diabetic complications and metabolic control. Forty Chinese and Indian patients participated in the Diabetic Society of Singapore National Home Blood Glucose Monitoring (HBGM) Programme. The clinical progress, the blood glucose and glycosylated haemoglobin concentrations, and the platelet aggregation of the aforementioned patients were studied over a 6-month period; the results were compared with those from a matched, albeit smaller, control group of 18 diabetic patients who were on treatment but not in the HBGM programme. At the end of the six month period, three patients in the control group showed clinical deterioration of peripheral neuropathy in contrast to one patient on HBGM. Due to the small number of patients, the difference in the findings was not statistically significant. Patients on HBGM demonstrated significant improvement in mean grouped blood glucose profile values, 135 +/- 8 to 118 +/- 5 mg/dl, p less than 0.01, and glycosylated haemoglobin levels, 10.3 +/- 0.4 to 9.3 +/- 0.3%, p less than 0.01. The platelet aggregability was unchanged. In contrast, patients in the control group developed a significant increase in platelet aggregation (30 +/- 4% to 37 +/- 5%, p less than 0.05), although the blood glucose and glycosylated haemoglobin concentrations were not significantly altered. This study demonstrated that patients on a six-month HBGM programme were able to achieve improved glycaemic control associated with a trend towards decreased deterioration of diabetic neuropathy and platelet aggregability. PMID- 4037683 TI - Pyogenic hepatic abscess and diabetes mellitus--a probable association. AB - Four patients with pyogenic hepatic abscesses are reported. There were three females and one male with an age range of 36-75 years. In all the cases, diabetes mellitus was associated. Confirmation of the abscesses was obtained by liver scanning or ultrasonography, or both. In one patient, the clinical course was complicated by sympathetic pericardial effusion with right heart failure. Two patients had percutaneous transhepatic drainage of the abscesses under fluoroscopy. All four patients eventually required laparotomy and open drainage of the abscesses. Diabetic control was achieved with insulin therapy. The common causative organism in all instances was the Klebsiella species. Three patients recovered. The remaining one developed hypotension post-operatively and died of brain-stem infarction and the hepato-renal syndrome. PMID- 4037684 TI - Assessment of complications in children with insulin-dependent diabetes mellitus. AB - Nineteen children with insulin-dependent diabetes mellitus in the University Department of Paediatrics were assessed for complications of diabetes. 36.8% showed marked growth stunting, and half of the patients who attained puberty had a delayed onset of puberty. 42% showed limited joint mobility. Almost all the patients developed hypertrophic lipodystrophy while only 5 patients developed reversible lipoatrophy. Abnormal nerve conduction velocities were found in all 17 patients tested, with more of sensory nerve involvement. A significant correlation was found between duration of disease and the extent of neuropathy. Evidence of nephropathy was found in 5 patients, 2 of whom showed impaired renal function. One patient had background retinopathy, another had proliferative retinopathy and 2 patients developed cataracts. The high prevalence of microangiopathic complications in these children is probably related to their previous poor diabetic control and it is hoped that with home blood glucose monitoring to improve their control, these complications may be arrested or minimized. PMID- 4037685 TI - Diabetes mellitus in peninsular Malaysia: ethnic differences in prevalence and complications. AB - Estimated prevalence of diabetes mellitus in Malaysia was about 2%. Diabetes was most common in Indians especially males and least common in Chinese. There was a slight male preponderance seen in Malays and Indians. Positive family history was obtained in 14% of cases most commonly in Malays, almost 1/3 of whom had more than one family member with diabetes. Familial association was uncommon in Chinese. Over 50% of patients were overweight. Obesity was noted in nearly 70% of female Malays and Indians while the majority of Chinese were not overweight. More than 80% of patients were non insulin requiring. Youth onset diabetes was considered rare; those 10 years and below were estimated to be only 0.4% and below 20 years of age between 2%-4% of the diabetic population. Females were twice as common than males in this type of diabetes and familial association was greater. Malnutrition-related diabetes and pancreatic calcification were not well documented but youth-onset non insulin requiring diabetics with mild symptoms but strong family history of diabetes were observed. More than half of hospital-based patients had evidence of complications, mainly amongst Malays and Indians. Hypertension was the most frequent associated disease followed by foot ulcers and ischaemic heart disease. Hypertension usually associated with chronic renal failure was most common amongst Malays while gangrenic ulcers and heart diseases were seen mainly in Indians. The major causes of death were chronic renal failure, myocardial infarction, ketoacidosis, stroke and septicaemia related to gangrene.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4037686 TI - Findings among 100 type 2 diabetics in a clinic in Penang, Malaysia, 1983-84. AB - A Specialist Clinic was commenced in August 1983, from the Medical School at Universiti Sains Malaysia, Penang, Malaysia to assess: 1) the present control and 2) the incidence of complications in a diabetic population already receiving primary health care at Penang General Hospital. The ethnic groups among the diabetics were Chinese (39%), Malays (26%) and Indian (35%). There was a greater percentage of Indians than would be expected from the ethnic distribution of the population of Penang. The results of the first 100 (43 males and 57 females) non insulin dependent diabetic patients are reviewed. The mean age was 54 years, 41% had relatives with diabetes, and all were taking oral agents. The diet comprehension and compliance were poor. 65% of the group, 54% of males and 75% of females were obese. The mean blood glucose was 11 m.mols/l (fasting) and 12.8 m.mols/1 (2 hours post prandial). The complications seen in the 100 diabetics were: albuminurea 41, skin infection 37, cataracts 35, hypertension 32, peripheral sensory neuropathy 32, retinopathy 22, ischaemic heart disease 19, autonomic neuropathy 10, impaired renal function 4 (urea or creatinine elevated), foot ulcer 2 and gangrene 1. Urinalysis for glucose at the Clinic showed very little correlation with blood glucose at the same time. Nine out of 43 males admitted to impotence on questioning. Comparisons of findings in Penang were made with recent studies in Singapore and Hong Kong. PMID- 4037687 TI - Hypoglycemia misdiagnosed as cerebrovascular accident. AB - Hypoglycemia can give rise to a variety of neurological signs and symptoms. This may occur in the absence of the well known signs of acute hypoglycemia taught to diabetics on insulin. In the past year, 6 patients with hypoglycemia were admitted with a diagnosis of cerebrovascular accident. They were all being treated with oral hypoglycemic drugs. The neurological signs all reversed immediately with the restoration of a normal blood glucose. Their circumstances of admission illustrate some of the difficulties in making the correct diagnosis in this group of patients. PMID- 4037688 TI - Blood glucose levels in non-diabetics on intravenous dextrose infusions. AB - Does a 5% dextrose infusion of up to 3 litres per 24 hours in a patient cause significant hyperglycemia if the patient is not a known diabetic? This small study showed that in 15 patients on such a drip not on steroids, the blood glucose level at least two hours postprandially did not rise above 140 mg%. On the other hand, another two patients on steroids had blood glucose levels above this value but below 180 mg%. PMID- 4037689 TI - Combined team management of diabetes mellitus in pregnancy. AB - 225 women with diabetes in pregnancy were managed by a team of obstetricians, physicians (endocrinologists) and paediatricians from the National University of Singapore. A protocol of management was formulated and followed. The incidence of 1.1% or 1 in 90 pregnancies was found, with significantly higher incidence in Indians and lower in Malays. There were 37 established diabetics and 188 diagnosed during pregnancy. Of these (188), 74 were gestational diabetics. All the women were treated with Insulin and Diet or Diet alone. 177 (79%) were treated with Insulin and Diet. Blood sugar profiles were done for monitoring diabetic control. 72.8% of the women were between para 0 and 1 and 85.2% between the ages of 20 and 34. 72.5% of the women delivered at 38 weeks gestation or later. 48.9% went into spontaneous labour, 32.4% were induced and 18.7% had elective caesarean section. 62.2% of the women had labour of less than 12 hours. The overall caesarean section rate was 41.7%. There were 3 stillbirths and 2 neonatal deaths. The perinatal mortality rate was 2.2%. Thirteen babies had congenital malformations (5.8%). 77.8% of the babies had Apgar score of 7 or more at 5 minutes after delivery. 79.1% of the babies weighed between 2.5 kgm and 3.9 kgm. Pre-eclamptic toxaemia was the commonest complication in pregnancy followed by Urinary Tract Infection and Polyhydramnios. Postpartum complications in the mother were confined to 14 women (6.2%), and wound infection or breakdown was the commonest cause. PMID- 4037690 TI - Extremes of foetal birthweight for gestation in infants of diabetic mothers. AB - 100 patients were registered at the Diabetic Clinic in 1981, where they were managed by a team of physician, obstetrician and paediatrician, based on a preset protocol. Only 92 patients were eventually analysed. The study showed a 1.3% incidence of pregnancies complicated by diabetes mellitus. The mean birthweights of infants of both gestational and established diabetics were heavier than that of the general population by race and gestation. 25% of the 92 infants of diabetic mothers have birthweight exceeding the 90th centile of population. Further division of the 92 patients into the "true gestational" diabetics, as shown by an oral glucose tolerance test performed 6 weeks post-natally, also showed a 25% incidence of macrosomia. Late antenatal booking, delayed detection of abnormal glucose tolerance and treatment attributed to the high incidence of macrosomia. Only one infant had birthweight below the tenth centile. There were no perinatal mortality in the 92 patients studied. Macrosomia is a common complication in infants of diabetic mothers despite a physician-obstetrician joint-care system. Also, the risk of having macrosomia amongst gestational diabetics is high. PMID- 4037691 TI - The role of the Diabetic Society of Singapore in promoting diabetes self care and education. PMID- 4037692 TI - Insulin dependent diabetes and goitre in a case of hypomelanosis of Ito (Incontinentia Pigmenti Achromians). AB - Incontinentia Pigmenti Achromians (IPA) or, more aptly, Hypomelanosis of Ito is now largely accepted as a Neurocutaneous Disorder. Studies, so far, have focussed on the ultrastructural abnormalities and to our knowledge, there have been no attempts to ascertain if there is a particular HLA pattern. We describe an interesting case where IPA occurred in association with Insulin Dependent Diabetes as well as a goitre, suggesting that HLA studies may well be worthwhile. The literature is also reviewed. PMID- 4037693 TI - Continuous subcutaneous insulin infusion therapy in Japan, 1984: a survey by questionnaires. AB - A country-wide survey of the continuous subcutaneous insulin infusion (CSII) therapy was carried out in the summer of 1984 in Japan. Questionnaires were mailed to doctors of 456 diabetes clinics and other questionnaires were distributed to patients taking CSII therapy by salesmen of the infusion pump makers. 275 doctors and 86 patients responded to the questionnaires. CSII therapy was conducted in 110 clinics (40%), but it was done mostly in inpatients. Decrease in blood glucose (91%) and improvement of general body condition (65%) were achieved by the therapy, but cutaneous complications, such as skin reaction to the tapes (33%), pigmentation (46%), induration (35%) and lipodystrophy, and hypoglycemic (83%) or ketoacidotic (16%) episodes were experienced in many cases. 211 doctors predicted bright prospects for the CSII therapy, 86 (41%) speculated a spread in the popularity of the therapy and 44 (21%) opined that the therapy was a passing phenomenon (only a fashion). PMID- 4037694 TI - Orthopaedic management of diabetic foot lesions. AB - Vascular disease and neuropathy play a major role in the pathogenesis of diabetic foot lesions. Trauma and infection are aggravating factors. With local aggressive treatment, many of these limbs can be salvaged. A classification of lesions of the diabetic foot is presented. Criteria for conservative as well as ablative surgery based on clinical studies are discussed. PMID- 4037695 TI - Insulin-dependent diabetes mellitus: strategy for prevention and management. AB - Insulin-dependent diabetes mellitus (IDDM) is inherited in a multifactorial manner with polygenes and environmental factors contributing to its emergence in a particular individual. The evidence for such a mode of inheritance is reviewed. One of the most important genetic roles is that played by the HLA genes on chromosome 6 and the different alleles which increase or decrease susceptibility in Caucasians, Japanese, Singapore Chinese and Shanghai Chinese are described. It is inferred that these alleles are different in different ethnic groups. The other genes which are important are unknown. The environmental influences are less well known although viral infections may act as triggers. Because the morbidity and mortality are still extremely serious in IDDM patients in spite of insulin therapy, it is proposed that preventive measures should be instituted in families prone to IDDM. The role of prenatal diagnosis is discussed especially in those families with multiple HLA susceptibility genes present. Great care paid to management of hyperglycemia from onset of the disease may reduce future morbidity and mortality. PMID- 4037696 TI - Genetic and environmental influence in the epidemiology of noninsulin-dependent diabetes mellitus: a global perspective. AB - Refinement of the classification of diabetes mellitus to include two major categories, insulin dependent (IDDM) and noninsulin-dependent (NIDDM) and the recent attention paid to the standardization of epidemiological techniques have led to much new information on the epidemiology of the disease. Support for the notion of genetic influence in the development of NIDDM has come from twin studies, but the search for specific genetic markers for NIDDM has been largely unproductive to date. There is increasing scepticism as to the utility of the chlorpropamide-alcohol flush as a genetic marker for NIDDM. The large disparity in the frequency of NIDDM between populations provides indirect support for the genetic hypothesis, as do recent studies of the association between NIDDM and ancestral genetic admixture. Obesity has long been considered a causal factor in the aetiology of NIDDM, though the strength and consistency of this relationship is now being questioned. The strength of the association between obesity and NIDDM has been shown to vary depending on the presence or absence of a family history of the disease. There is further preliminary evidence to suggest that association between obesity and NIDDM may vary in strength between populations, and between the sexes. Little evidence has so far emerged for a role of quantitative or qualitative aspects of diet in the aetiology of NIDDM. This may be due, in part, to the imprecision of current techniques for dietary estimation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4037697 TI - Endoscopic, histological and ultrastructural correlations in the diagnosis of colitis. AB - The accuracy of the endoscopic diagnosis, found at fiberoptic distal-colonoscopy, was assessed by correlation with the histological findings of multiple colo rectal biopsies. Of 25 subjects with normal colon at endoscopy, 18 (72%) had normal histology, while 7 (28%) had histological evidence of mild non-specific colitis (6 cases) or Crohn's colitis (one case). Of 15 cases with endoscopic appearance of mild colitis, histological sections showed mild non-specific colitis in 12 (80%), idiopathic ulcerative colitis in one and Crohn's colitis in another. In 12 patients with an endoscopic diagnosis of moderate-severe colitis, histology confirmed moderate to severe idiopathic ulcerative colitis in 9 (75%) and severe Crohn's colitis in 2. Pseudomembranous colitis was confirmed by histology in 2 out of 3 cases detected by endoscopy. Electron-microscopy, although amplifying the histological findings, did not provide any specific diagnostic information. It is concluded that histological studies of multiple colo-rectal biopsies can significantly improve the diagnostic accuracy of distal colonoscopy. Biopsies should therefore be obtained routinely in colonoscopy even if the appearances look normal. PMID- 4037698 TI - Opsite, a synthetic burns dressing. AB - Opsite, a sterile, occlusive, adherent, polyurethane film has been used in a prospective study involving 150 cases of partial thickness burns. All cases were admitted to the Department of Plastic Surgery, Singapore General Hospital. The patients' ages ranged from infants to the elderly. All sites of the body were tried on Opsite except the head and face and total burns areas applied with opsite varied from less than 5% to 25%. 80% of cases did well, 20% had to have the dressing discontinued for various reasons, the most common being infection. The advantages were in the ease of wound observation, patient comfort, early mobilisation and relative economy. Opsite is a suitable burns dressing for the partial thickness burns especially of the trunk and limbs and is very useful in children. The complications are relatively few and minor. PMID- 4037699 TI - Tumoral calcinosis--a case report. AB - Tumoral Calcinosis is a well established but rare clinical entity. It was first described in 1899, and since then, scattered reports have occurred in the literature from many parts of the world. The main controversy lies in the aetiology of the condition. One such case is presented in this paper, along with a review of the literature. PMID- 4037700 TI - Hyperglycemic macrocytosis in electronically determined mean corpuscular volume. Use of three different automatic cell counters. AB - Spurious macrocytosis in electronic cell counters has been associated with hyperglycemia. The increased mean corpuscular volume (MCV) is thought to be secondary to osmotic disequilibrium between the erythrocyte and the diluent used in the automatic cell counters. Employing three different hematology cell counters, the effects of increasing concentration of glucose (400 mg per dl to 2000 mg per dl), at different temperatures and after various incubation periods were studied. In addition to macrocytosis being temperature and glucose concentration dependent, the magnitude of cell size variation also depends on the type of instrument used. PMID- 4037702 TI - The occurrence and properties of a serum hepatic antigen in various liver diseases. AB - A liver antigen, LA-1, was detected by immunoelectrophoresis in the sera of 79 percent of patients with viral hepatitis A, 77 percent of patients with viral hepatitis B, and 62 percent of patients with alcoholic hepatitis. The occurrence of LA-1 was lower in liver cirrhosis (28 percent) and primary extra-hepatic disorders (18 percent) and absent in the sera of healthy subjects. Liver antigen, LA-1, is detectable in human kidney, lung, spleen, heart and skeletal muscle, and rhesus monkey liver; however, it is not found in the livers from dog, rat, cat, or pig. This antigen is characterized as a protein with beta-globulin electrophoretic mobility and a molecular weight in the range 67,000 to 80,000, which distinguishes it from liver ferritin and previously defined bile antigens and liver-specific antigens detected in sera from patients with liver diseases. The presence of LA-1 in serum appears to denote non-specific liver injury. PMID- 4037701 TI - Electrothermal atomic absorption spectrophotometry of nickel in tissue homogenates. AB - A method for analysis of Ni concentrations in tissues is described, which involves (a) tissue dissection with metal-free obsidian knives, (b) tissue homogenization in polyethylene bags by use of a "Stomacher" blender, (c) oxidative digestion with mixed nitric, sulfuric, and perchloric acids, and (d) quantitation of Ni by electrothermal atomic absorption spectrophotometry with Zeeman background correction. The detection limit for Ni in tissues is 10 ng per g, dry weight; the coefficient of variation ranges from 7 to 15 percent, depending on the tissue Ni concentration; the recovery of Ni added in concentration of 20 ng per g, dry weight, to kidney homogenates averages 101 +/- 8 percent (mean +/- SD). In control rats, Ni concentrations are highest in lung (102 +/- 39 ng per g, dry weight) and lowest in spleen (35 +/- 16 ng per g, dry wt.). In descending order of Ni concentrations, the tissues of control rats rank as follows: lung greater than heart greater than bone greater than kidney greater than brain greater than testis greater than fat greater than liver greater than spleen. In rats killed 24 h after sc injection of NiCl2 (0.125 mmol per kg, body weight) Ni concentrations are highest in kidney (17.7 +/- 2.5 micrograms per g, dry weight) and lowest in brain (0.38 +/- 0.14 micrograms per g, dry weight). In descending order of Ni concentrations, the tissues of NiCl2-treated rats rank as follows: kidney much greater than lung greater than spleen greater than testis greater than heart greater than fat greater than liver greater than bone greater than brain.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4037703 TI - [Effects of different acute and chronic stresses on general growth and adrenal cortex activity in rats]. AB - Stress due to ether, physical strain, and exhaust gas applied to pubescent male rats either acutely or chronically, (15 days or 2 months) always induce a similar increase of plasmatic corticosterone. However, they induce other different changes (food intake, body growth, protein yield, and the relative growth of the liver, the testis and the heart). Thus we define for each type of aggression a non-specific action, characterized by a more or less similar activation of the pituitary-adrenal axis and an other specific action. PMID- 4037704 TI - [Effects of septal lesions on the response of vasopressin to angiotensin II]. AB - Electrolytic lesion of the medio-ventral septal (MVS) area produces a sustained increase in daily water intake and urine output. This polyuria and hyperdipsia are associated with decreased levels of circulating radioimmunoassayable ADH. In addition, the usual ADH release to angiotensin II observed in normal controls and sham-lesioned rats was markedly blunted in MVS-lesioned animals. PMID- 4037705 TI - [Isolated gynecomastia disclosing limited androgen resistance]. PMID- 4037706 TI - [Primary empty sella turcica. Analysis of 14 cases and review of the literature]. AB - 14 patients (13 women, 1 man) presenting with primary empty sella had endocrinologic and radiological investigations. 8 women are obese, 5 multiparous. Initially, headaches have needed a radiological study of sella turcica in 8 cases (57%). Pneumoencephalography and/or CT scan have led to diagnosis; but in 3 cases, a suspected associated pituitary adenoma justified a surgical exploration. In one case, a GH-secreting microadenoma was found, in both other cases histologic studies revealed fibrous or normal pituitary. Endocrine findings were normal, regarding to gonadotrophs, corticotrophs and thyreotrophs. GH was blunted in four cases, below 5 ng/ml during insulin tolerance test. In 9 cases, GH rose to 19,51 +/- 10,03 ng/ml (mean +/- S.D.). In 13 patients, serum prolactin was normal: 7,1 +/- 3,9 ng/ml (normal values 2 -20 ng/ml), elevated in the last case: 112,5 ng/ml. One year later, two patients did not show any modification on clinical, radiological or endocrine data. Physiopathology of intrasellar arachnoidocele is discussed: intrasellar extension of subarachnoid space may be due to diaphragm insufficiency and disturbances of dynamics of cerebrospinal fluid, flattening the otherwise normal pituitary gland. PMID- 4037707 TI - [Changes in gastrointestinal motility in the diabetic]. AB - The frequency and pathophysiology of disorders of gastro-intestinal motility associated with diabetes are poorly understood. Gastroparesis is often misdiagnosed, although it can be responsible for diabetic instability. Constipation is the most frequent gastro-intestinal symptom, although the patient may present alternating episodes of diarrhoea and constipation. The pathophysiology of these disorders is still poorly understood. It could well be caused by diabetic neuropathy. PMID- 4037708 TI - [Primperan: recent pharmacological data on its gastromotor effect]. AB - Two types of pharmacological action explain the therapeutic effectiveness of Primperan in gastroenterology: an anti-emetic effect due to a central dopaminergic mechanism and a motor effect on the gastro-intestinal tract due to a cholinergic mechanism. Research is currently underway to explain the origin of the cholinergic potential of metoclopramide. PMID- 4037709 TI - [Primperan during pregnancy]. AB - The indications for Primperan during pregnancy are presented: vomiting and pyrosis, prevention of Mendelsohn's syndrome when general anaesthesia is required during pregnancy or labour. 20 years of pharmacovigilance confirm the good maternal and foetal tolerance of this drug. PMID- 4037710 TI - [Primperan and the dyspeptic syndrome]. AB - Primperan modifies the behaviour of the antro-pyloro-duodenal functional unit and is therefore a logical treatment for dyspeptic disorders. In a double blind study, the oral administration, before meals, of 30 mg of Primperan per day for 15 days was found to be significantly superior to a placebo in the correction of dyspeptic symptoms. PMID- 4037711 TI - [Primperan and digestive disorders in aged subjects]. AB - The consequences of aging on the oesophagus and stomach are described. The disorders induced by these physiological changes are accentuated by the life style and the socio-economic conditions. Based on three clinical studies conducted in elderly subjects, the authors discuss the diagnostic and therapeutic value of Primperan: facilitation of endoscopy, gastro-oesophageal reflux, dyspeptic disorders. PMID- 4037712 TI - [Value of oral primperan in the treatment of migraine]. AB - The association of Primperan with antimigrainous drugs, such as salicylates and paracetamol, can reduce the duration of the migraine. The mechanism of this action is studied: by accelerating the gastric emptying, which is delayed during the migraine attack, Primperan enables the analgesics to reach their site of absorption more rapidly and, consequently, to be more rapidly effective. The activity of the oral administration of Primperan is demonstrated. PMID- 4037713 TI - [Value of primperan in digestive studies]. AB - The majority of gastro-intestinal investigations cause disturbances of secretion or gastric tonicity and motility, which can interfere considerably with the examination. It is therefore essential for the doctor to prevent these disorders by equilibrating the gastro-intestinal function. Primperan is incontestably the molecule of choice in this field, because of the specificity and the constancy of its action in the gastro-intestinal tract and because of its excellent tolerance. PMID- 4037714 TI - [Application of an original technic in the evaluation of gastric emptying to the study of primperan]. AB - The ingestion of radio-opaque granules during a meal enables the radiological study of gastric emptying under physiological conditions. The evacuation of the granules is well correlated with that of solids. After the development of a pharmaco-clinical model of hyposthenic dyspepsia, this technique was used by the authors to evaluate the influence of Primperan on gastric emptying after a dyspeptogenic meal in 12 volunteers. Following the randomised intravenous injection of either 20 mg of Primperan or a placebo, 5 to 7 minutes before the dyspeptogenic meal, the number of granules remaining in the stomach over time was used to measure the rate of gastric emptying. Primperan significantly accelerated the gastric emptying of the dyspeptogenic meal in comparison with the placebo (p less than 0.01). PMID- 4037715 TI - [Highlights of the physiopathology of gastroesophageal reflux]. AB - Manometric studies have shown that the principal barrier against gastro oesophageal reflux is the inferior oesophageal sphincter. The factors capable of physiologically and pathologically modifying the sphincter pressure are analysed. Other factors may be involved as well as a decrease in the pressure of the inferior oesophageal sphincter: the length of the abdominal oesophagus, the oesophageal clearance, delayed gastric emptying, duodeno-gastric reflux. Thus, in many patients, gastro-oesophageal reflux reflects a disturbance of the motility of the upper gastrointestinal tract and not just the oesophagus. PMID- 4037716 TI - [Highlights of the dyspeptic syndrome in 1985]. AB - Many hypotheses have been proposed to explain the development of non-lesional dyspepsia: various authors suggest an excessively delayed gastric emptying, or excessive gastric secretions or an intestinal cause. The actual pathophysiology of these disorders is probably multifactorial. In the absence of more precise data, we nevertheless have a symptomatic treatment which is often effective. The most severe dyspeptic disorders respond very well, particularly to molecules which act on the tonicity and the motility of the gastro-intestinal tract. PMID- 4037717 TI - Regional and social analysis of height variation in a contemporary British sample. AB - The height distributions of 11-year-old boys and girls and their parents (N = 33 000) comprising the National Child Development Study are reported. The variance in height was found to differ significantly between social classes for all three family positions (father, mother and child). Analysis of variance and cluster analysis revealed that stature distributions in all three family positions is more socially rather than regionally differentiated. PMID- 4037719 TI - Alternative explanations for normal variability in antithrombin-III levels. AB - Data collected in a study of ATIII deficiency also suggested familial variability of blood clotting times amongst genotypically normal individuals. A study of this variability under a variety of models demonstrates a clear age effect and within sibship similarity. There is also a clear parental effect, which could be either environmental or genetic. Even when parental effects are taken into account there remains some excess similarity between sibs, but the increase in log-likelihood provided by this component is no longer highly significant. PMID- 4037718 TI - Chest dimensions of European and Aymara children at high altitude. AB - This study compares the chest dimensions of European children raised at high altitude with those of Andean natives. The samples consist of 216 children between 8 and 14 years who attend the private French School in La Paz, Bolivia and 253 Aymara children of the same age who reside in the rural country of Arncoraimes, Bolivia. Compared to the Aymara children, the European children have larger chest depths and chest widths, but have smaller chest dimensions relative to stature. There is no difference between the two groups in the ratio of chest width to chest depth. The small relative chest size of the European children further expands the range of variation in chest dimensions among high altitude populations. PMID- 4037720 TI - Serogenetic studies on the inhabitants of Tristan da Cunha. AB - The inhabitants of Tristan da Cunha, a remote island in the South Atlantic, number about 300 and are direct descendants of a small number of individuals who settled there in the first half of the nineteenth century. Some serogenetic studies were carried out on the islanders when they were evacuated to England in 1961 but 160 individuals have now been tested for a much wider range of gene markers. No variation was found at 15 loci while considerable variation was encountered at 12 loci. In particular, the high frequency of A1 and the complete absence of A2 in the ABO system was confirmed; the high frequency of Ro (cDe) in the Rhesus system and GdA, an allele at the G6PD locus, as well as the presence of three haplotypes in the Gm system (Gm1,5,6,14,17, Gm1,5,6,17 and Gm1,5,13,14,17) confirm the known historical origin of the women founders who came from St Helena. Although the degree of inbreeding is high there is no significant deficiency of heterozygotes in the eight informative systems. PMID- 4037721 TI - Android (centralized) obesity and somatotypes in men: association with mesomorphy. AB - The relationship between body fat distribution patterns and somatotype among 824 men was sought from Sheldon, Dupertuis and MacDermott's Atlas of Men (1954). The men were classified photoscopically into obese, overweight and normal weight classes and then into android (central), intermediate and gynoid (generalized) classes of body fat patterning independently and blindly by two observers. Android fat men were found by both observers to be older and more often classed as obese than gynoid fat men. The android obese were significantly more mesomorphic and less endomorphic than the gynoid obese (P less than 0.01). Results suggest that android obesity involves more than an upper body distribution of subcutaneous fat: it is a deep body obesity involving excess lean body mass as well. PMID- 4037723 TI - Origin and fate of cholesterol in rat plasma lipoproteins in vivo. I. Qualitative analysis. AB - Rats were conditioned to ingest a 15-gram dietary mixture, in a single daily meal, between 6:00 and 9:00 a.m. Labeled cholesterol was introduced into the organism through four different physiological routes: ingestion of 14C cholesterol, injection of 14C-acetate, injection of red cells or plasma whose cholesterol was tritium-labeled. The specific radioactivities of free and esterified cholesterol, in the different plasma lipoproteins and in the major organs, were measured at various time spans after the introduction. The results revealed a different source of cholesterol in chylomicrons and VLDL discharged by the intestine: the chylomicrons would principally carry esterified cholesterol coming from the intestinal contents, while esterified cholesterol coming from the intestinal wall was found mainly in VLDL. The free cholesterol of these lipoproteins would initially have the same origin as esterified cholesterol but rapid free cholesterol exchanges would introduce precociously cholesterol coming from other structures. The results demonstrated the significant role of the intestine in cholesterol synthesis and revealed that of VLDL in the internal secretion of cholesterol by the intestine. Chylomicrons also appeared to play a significant role in this secretion, by way of exchanges between intestinal cells and chylomicrons in the process of formation. Finally, the results suggested the existence of esterified cholesterol transfers from HDL to lower density lipoproteins (chylomicrons, VLDL and possibly LDL). PMID- 4037722 TI - [Effect of varying vitamin B6 intake levels on the vitamin B6 status of fetuses and reproductive organs]. AB - In order to study the influence of varying vitamin B6 intake levels on the reproductive performance and the vitamin B6 status of fetuses and reproductive organs, 30 pregnant rats (Sprague Dawley strain) were fed a semisynthetic casein diet supplemented with 1, 6, 12, 24 and 48 mg vitamin B6/kg throughout pregnancy. On days 19 of pregnancy the rats were killed. Fetuses, placenta, amniotic fluid, amnion, uterus and mammary gland were analysed microbiologically for their vitamin B6 content. Reproductive performance was not influenced by the dietary treatment. Vitamin B6 concentrations in fetuses, placenta and amniotic fluid of mothers treated with the low 1-ppm vitamin B6 diet were significantly decreased. At a vitamin B6 supply of 6 ppm, however, tissue saturation was already reached in these organs. Accordingly, the whole vitamin B6 retention in the reproductive product plateaued at an intake level of 6 ppm vitamin B6 at 37 micrograms vitamin B6 per animal. These results indicate therefore that a level of 6 ppm dietary vitamin B6 is sufficient to guarantee an optimum vitamin B6 status in the reproductive product, and higher vitamin B6 supplementations showed no further effect on the parameters investigated. PMID- 4037724 TI - Origin and fate of cholesterol in rat plasma lipoproteins in vivo. II. Modelling of cholesterol absorption and its release into plasma lipoproteins. AB - After a single ingestion of a diet containing 14C-cholesterol, cholesterol radioactivity in the stomachal and intestinal contents, in the different organs and in the very low density lipoproteins (VLDL) and chylomicrons was measured at different times during 2 days. Based on the results, a quantitative model of cholesterol absorption and of its release into the VLDL and chylomicrons has been elaborated. This model takes into account the different processes implied in the turnover of intestinal cholesterol and that of the entire organism. It constitutes a coherent whole (satisfactory simulations for the variables studied, suitable mass balances for each compartment and the absence of major contradictions with preexisting quantitative data). Once again the model demonstrates the important part played by the intestine in rat cholesterol system dynamics. It takes into account the existence of two related exogenous and endogenous cholesterol pools from which the cholesterol released by the intestine into the chylomicrons and VLDL originates. The results suggest the existence of an important esterified cholesterol uptake from other plasma lipoproteins by the chylomicrons. PMID- 4037725 TI - [Origin and fate of cholesterol in rat plasma lipoproteins in vivo. III. Demonstration and measurement of the flow rate of HDL esterified cholesterol to the chylomicrons]. AB - A study has been carried out to measure the transfer rate of esterified cholesterol from the HDL into the chylomicrons, as previously suggested. Rats were intravenously injected with cholesterol-labelled plasma or red cells. The specific activity of esterified cholesterol of HDL and chylomicrons was measured during 12 h following injection. Results were treated by compartmental analysis. The transfer rate was 0.21-0.22 h-1 with an uptake rate of chylomicrons by the liver of 8 h-1 (t1/2 5 min). This represents a 0.8 mg h-1 flux of esterified cholesterol from HDL into chylomicrons, i.e., in our conditions, 75% of the total input into the chylomicrons esterified cholesterol. This process could be the major way for the disappearance of HDL esterified cholesterol. PMID- 4037726 TI - Effect of spinning and additional cross-linking with dialdehyde starch or aluminum ions on the digestibility and quality of casein-Vicia faba protein isolate mixtures. AB - Studies were made in adult rats using an isotopic 15N method. Whole egg, wheat, casein and Vicia faba protein isolate served as reference proteins. The diets were isonitrogenous and feed intake was adjusted to the maintenance energy level. Variations in true N digestibility were small (91.8-96.1%). The amount of metabolic fecal nitrogen in animals receiving the diet containing wheat was 9.4 mg/100 g body weight compared with 4.9-5.8 mg in the other diets. The differences in nutritional quality for maintenance between proteins of plant and animal origin were small. However, spinning (alkaline treatment) and additional cross linking with aluminum ions or dialdehyde starch affected the nutritional quality for maintenance. PMID- 4037727 TI - Influence of different supplements of N-3 polyunsaturated fatty acids on blood and tissue lipids in rats receiving high intakes of linoleic acid. AB - The influence of a supplement of linseed oil (LO), rich in linoleic acid (C18:3,n 3), was compared with one of fish oil (MaxEPA) rich in eicosapentaenoic acid (C20:5,n-3) and docosahexaenoic acid (22:6,n-3) on blood and tissue lipids in weanling rats receiving a high intake of linoleic acid. Both the LO and the MaxEPA supplement decreased plasma cholesterol concentrations. The MaxEPA supplement but not the linseed oil supplement also decreased the concentrations of plasma triglycerides and HDL cholesterol. The proportion of C20:5,n-3 was markedly increased in the platelet and erythrocyte lipids by the MaxEPA supplement but not in tissue lipids. However, the increase in the proportion of C20:5,n-3 in the platelet was small compared with other studies. Both supplements led to an increase in the proportion of C22:6,n-3 in blood and tissue lipids but the MaxEPA supplement was more potent than the LO supplement. The most marked change was observed in the heart lipids. These changes were accompanied by reciprocal changes in the proportions of arachidonic, adrenic and docosapentaenoic acid. PMID- 4037728 TI - Eurofoods: towards compatibility of nutrient data banks in Europe. PMID- 4037729 TI - Enzyme-linked immunosorbent assay for measurement of penicilloyl groups. AB - An enzyme-linked immunosorbent assay for measuring penicillin groups is described. Alkaline phosphatase conjugated to penicilloyl residue was reacted with purified anti-penicilloyl antibodies coated upon polystyrene plates. The inhibition of this reaction allowed a specific determination of penicilloyl residues at the picomole level. This assay was applied to the study of the penicilloyl groups linked to human albumin and to the measurement of some of these groups after enzymatic degradation or physical modifications of the albumin molecule. PMID- 4037730 TI - Methodological aspects of the 6-day subrenal capsule assay for measuring the response of human tumors to anticancer agents. AB - Methodological aspects of testing chemosensitivity by the 6-day subrenal capsule (SRC) assay in immunocompetent mice were investigated. Human tumor xenografts, serially transplanted in athymic nude mice, were used as source of material. All drugs were given by the intravenous route. Administration of the drugs on days 1 and 2 gave the same results as when they were given daily for 5 days in equitoxic total doses, and a clear dose-response relationship was demonstrated. High reproducibility was found with different anti-cancer agents when 15 different tumors (4 melanomas, 7 soft tissue sarcomas, 2 colon carcinomas, and 2 lung carcinomas) were tested repeatedly over a period of several years. The tumors examined showed individual chemosensitivity profiles. The same ranking of drugs was found when the results in the SRC assay were compared with those obtained in the sc nude mouse model, using the same tumors (a colon carcinoma and a leiomyosarcoma), supporting the validity of the SRC assay. Altogether, the results strongly support the view that the 6-day SRC assay in immunocompetent mice is a useful method for assessing the response of human tumors to anticancer agents. PMID- 4037731 TI - A phase II study of alternating combination chemotherapy in 55 myeloma patients. A comparison with non-alternating combination chemotherapy and treatment with a single cytostatic. AB - Fifty-five consecutive patients with stage II and III myeloma were treated at 7 centers with alternating combinations of 7 cytostatics and prednisolone. 30/48 evaluable patients responded to the combination chemotherapy, 10/55 patients died within 15 months, and the median survival was 40 months. No advantage could be shown over a previous non-alternating combination of two cytostatics. However, stage III patients had a significantly better survival statistically (p less than 0.05) than earlier patients from the same center given only one cytostatic. PMID- 4037732 TI - Mitogen stimulation of blood lymphocytes from patients with primary intracranial tumors. Correlation to histological tumor type. AB - Blood lymphocytes from 125 patients with primary intracranial tumors were examined for proliferative responses to PHA and PPD in parallel with lymphocytes from sex- and age-matched controls. The tests were performed prior to surgery, radiotherapy, or chemotherapy and a histological diagnosis was obtained in all cases. Depending on tumor type, patients were divided into the following four histological groups: astrocytomas, oligodendrogliomas, malignant gliomas (anaplastic astrocytomas and glioblastomas), and miscellaneous tumors (mainly meningiomas). PHA-responses were approximately 10% lower in patients with malignant gliomas not receiving corticosteroids in comparison to corresponding controls. No significant differences were observed in the other groups of patients if not being treated with steroids. PPD-responses were largely similar in all groups of non-steroid treated patients. In the corticosteroid treated groups PHA-responses were significantly reduced in patients with oligodendrogliomas and malignant gliomas, but this was not true of those with astrocytomas or those in the group with miscellaneous tumors. The mean steroid doses given at the time of testing were similar in all four patient groups. The treatment period was longest in malignant gliomas but reasonably similar in the other three groups. It is speculated that PHA-responses of lymphocytes from patients with oligodendrogliomas may exhibit an increased steroid sensitivity. PMID- 4037733 TI - Capacity of sera from patients with primary intracranial tumors to support mitogen stimulation of blood lymphocytes. Correlation to histological tumor type. AB - Sera from 125 untreated patients with various histological types of primary intracranial tumors were examined for the capacity to support proliferative responses of lymphocytes to PHA and PPD in vitro. It was observed that sera obtained from groups of non-corticosteroid treated patients with astrocytomas, malignant gliomas (anaplastic astrocytomas and glioblastomas), and miscellaneous tumors (mainly meningiomas) did not differ significantly from sera obtained from a group of healthy subjects. However, sera from a group of patients with oligodendrogliomas exhibited a significantly reduced capacity to support PHA- and PPD-responses of both autologous and allogeneic lymphocytes. Corticosteroid treated patients seemed to have reduced serum activities regardless of histological tumor type. It is not known whether sera from patients with oligodendrogliomas contain increased amounts of factors which inhibit mitogen responses of lymphocytes, or whether they contain reduced amounts of factors which support stimulations in vitro. PMID- 4037734 TI - The synthesis of prostaglandins by the Nb rat prostate tumor. AB - Carcinomata of the prostate animal model systems have been used in the past to evaluate chemotherapy. The Nb rat model is an ideal model to study prostate cancer, as it has two separate tumor types, one that is androgen-insensitive and one that is androgen-sensitive. In this paper the results of the prostaglandin synthesis release assay on an antigen-insensitive tumor are presented. This is a means to further characterize this tumor. PMID- 4037735 TI - Interactions between estrogens, prolactin, and growth hormone on the growth of N nitrosomethylurea-induced rat mammary tumors. AB - Rats bearing N-nitrosomethylurea-induced mammary tumors regressing after ovariectomy were assigned to control or treatment groups. All control tumors continued to regress, while the serum prolactin levels were subnormal. Estrogen replacement stimulated tumor regrowth, and increased the serum prolactin. Pergolide further suppressed the postovariectomy serum prolactin, and all tumors continued to regress. When estrogen and pergolide were given together, 32% of tumors progressed despite low serum prolactins. Ovine prolactin, delivered to ovariectomized rats at a rate of 40 micrograms/hr, caused 3 of 10 tumors to progress, 3 to become static, and 4 to continue regression. Prolactin also maintained the growth of 4 of 8 tumors after hypophysectomy, and arrested regression of 3 others. Posthypophysectomy regression was also prevented and growth maintained by the simultaneous administration of estrogen and growth hormone. PMID- 4037736 TI - Phenotypic changes of Ab hamster melanoma during long-term culture. AB - Cells of the Ab hamster amelanotic melanoma in primary cell culture have previously been shown to melanize rapidly, detach from the glass substratum and lose the ability to proliferate in vitro. Recent work demonstrates that when the Ab cells are subcultured prior to a complete loss of proliferative ability, the above processes occur in the 1-3 passages. In about half of our attempts, long term cultures of Ab cells could be established from the few cells which remained attached to the glass during one of these first passages and resumed proliferation after a several-week period. The established long-term cultures showed a very low degree of melanization. Tumors which ensued from a reimplantation into hamsters of cells from one established long-term culture differed markedly from the original Ab melanoma in their phenotypic properties. PMID- 4037737 TI - Phase II trial of elliptinium in advanced renal cell carcinoma and carcinoma of the breast. AB - Elliptinium, 100 mg/m2 i.v. weekly, was administered to 14 patients with advanced renal cancer and 4 with breast cancer. There were no responses in 11 adequately treated patients. An unexpectedly high incidence of xerostomia, allergic, and hemolytic reactions were observed, which resulted in cessation of the trial. Recent data suggest polymer formation occurs with reconstituted elliptinium, and further trials are warranted when a new formulation is available. PMID- 4037738 TI - Variation of pH of mammary tumour cytosols: potential influence on steroid receptor assay. AB - Mammary tumour cytosols prepared for steroid receptor assay showed pH values above or below 7.3-7.5 in 50% of the samples. An increase of 0.6 pH units was observed after the addition of dextran coated charcoal. To test the sensitivity of the assay systems to pH changes, breast cancer cytosols were adjusted to pH between 6.0-9.0 before incubation with ligand at 0 degrees C. ER was then separated by isoelectric focusing in a pH gradient between 9.5-3.5 in a routine assay including a dextran coated charcoal step before focusing. PgR was assayed by electrofocusing as well as by a conventional DCC method and Scatchard plot. Unadjusted control cytosols were run in parallel. At pH above or below 7.0-8.0 recovery of receptor was reduced, the loss being most prominent at low pH. At low pH levels Scatchard plots appeared to be of curvo-linear shape. The effect of low intracellular tumour pH on receptor-ligand affinity in vitro may be of great importance as well in vivo, and should be taken into consideration in the therapeutic situation. PMID- 4037739 TI - On the role of aging in cancer incidence: analysis of the lung cancer data. AB - Age-specific lung cancer mortality rates for U.S. males and females from 1935 to 1978 were normalized to describe the percentage of total mortality in a given era which occurred at a given age interval. Correlation coefficients between age mortality patterns for various eras were calculated and found to be highly positive. We conclude that the shape of the lung cancer age-mortality pattern has remained remarkably constant despite dramatic changes in the carcinogenicity of the lung environment, and suggest that shape is determined by an invariant influence which is best attributed to some aspect of the aging process. PMID- 4037740 TI - Inhibition of protein synthesis by monoclonal anti-idiotypic antibody-ricin A chain conjugates in MOPC 315 myeloma cells. AB - Three monoclonal antiidiotypic antibodies (AIA) to MOPC 315 IgA, G3 (IgG2b), A2 (IgG1) and D10 (a hybrid molecule consisting of gamma 1 and gamma 2a heavy chains), were characterized with respect to their binding constants (Ka) to MOPC 315 mouse myeloma cells. The Ka of G3 and A2 was 10(8)/mole; and that of D10 was 3 X 10(7)/mole. The AIA did not bind to a non-immunoglobulin (Ig) producing subclone of MOPC 315 cells (MOPC 315.36). Immunotoxins derived by conjugating ricin A chain (RTA) to G3 and A2 but not to D10 preferentially inhibited protein synthesis in MOPC 315 over MOPC 315.36 cells. These results suggest that the effectiveness of these immunotoxins assessed on the basis of their targeted cytotoxicity against MOPC 315 cells was dependent on the Ka but not on the Ig subclass of the AIA component of the immunotoxin. PMID- 4037741 TI - Intestinal metaplasia of the stomach. I: Quantitative analysis in gastric peptic ulcer and in incipient adenocarcinoma in Japanese subjects. AB - A novel method of quantitation of the extent of intestinal metaplasia (IM) was applied to 50 resected stomachs from Japanese subjects; 25 with peptic gastric ulcer, 25 with incipient adenocarcinoma. The total length of the IM was significantly larger (p less than 0.05) in incipient adenocarcinomas than in peptic ulcers; the total length of the gastric mucosa analyzed being similar in the two groups. The intestinal metaplasia index (IMI; i.e. the ratio between IM and the length of the gastric mucosa analyzed) in incipient adenocarcinomas was significantly higher (p less than 0.05) than in gastric ulcers. In incipient adenocarcinomas, the IMI decreased significantly (p. less than 0.001) from lesser towards greater curvature. In peptic ulcers, the decrease was less abrupt. In 12 of the 25 specimens, the incipient adenocarcinoma was classified as intestinal type, and in the remaining 13 specimens as diffuse type. The total length of the IM was significantly larger (p less than 0.01) in specimens with intestinal type adenocarcinoma than in specimens with diffuse type; the total length of the gastric mucosa investigated being similar in the two groups. The IMI was significantly higher (p less than 0.01) in specimens containing intestinal type adenocarcinoma as compared to those with diffuse type adenocarcinoma. This was valid for the lesser curvature, for the mucosa adjacent to the lesser curvature, and for the mucosa by the greater curvature. From the results, it is apparent that intestinal metaplasia is a widely occurring phenomenon not only in specimens with intestinal type incipient adenocarcinoma or with diffuse type incipient adenocarcinoma, but also with benign peptic ulcer. The difference resides in that the metaplastic mucosa is more universally distributed in specimens with incipient intestinal adenocarcinomas (provided that longitudinal mucosal areas are considered in the comparison). The quantitative method herein reported will be applied in the future to compare the extent and distribution of intestinal metaplasia in gastric specimens from various geographical regions having disparate incidences of gastric ulcers and carcinomas. PMID- 4037743 TI - Activity of multiple sclerosis during pregnancy and puerperium. PMID- 4037742 TI - Enzymological and morphological changes in rat intestinal mucosa following treatment with alkylating sugar alcohol derivatives. AB - Wistar rats were treated with alkylating sugar alcohol derivatives, dianhydrogalactitol (DAG) and diacetyldyanhydrogalactitol (Diac-DAG), respectively. The drugs were intravenously administered as a single, bolus injection. The applied doses 2.5, 5, 10, 17 mg/kg DAG and 5, 10, 20, 40 mg/kg Diac-DAG were roughly equitoxic. The effect of these cytostatic agents was studied on the different marker enzymes (thymidine kinase, xanthine oxidase, alkaline phosphatase, sucrase, maltase) of the separated mucosa cells derived from the functional and proliferating zone of the small intestine. Both DAG and Diac-DAG inhibited the enzyme activities of the proliferating and mature enterocytes in a dose dependent fashion, primarily acting on the crypt specific thymidine kinase. The time dependent sequence in the biochemical alterations correlated well with the cytomorphological changes. The drug-induced damage was most pronounced 48 hours after a single treatment. The regeneration of the intestinal mucosa began on days 3 and 4 and was completed by day 7. Diac-DAG at equimolar concentration proved to be more toxic than DAG on the intestine as judged by the significantly higher decrease of protein content and xanthine oxidase activity. PMID- 4037744 TI - Sustained myoclonus in a woman with startle epilepsy. PMID- 4037745 TI - Marchiafava-Bignami disease: computed tomographic scan and magnetic resonance imaging. PMID- 4037746 TI - Alzheimer's disease: no alteration in the physical state of erythrocyte membrane glycoconjugates. PMID- 4037747 TI - 31P NMR study of cerebral metabolism during prolonged seizures in the neonatal dog. AB - The effects of prolonged bicuculline-induced seizures on cerebral blood flow and metabolism were determined in paralyzed, mechanically ventilated neonatal dogs. Transient changes occurring early in the course of status epilepticus included significant arterial hypertension, hypocarbia, elevation of plasma norepinephrine levels, and decline in brain glucose concentration. Cerebral blood flow remained elevated throughout the 45 minutes of seizure. Determination of cerebral metabolite values by in vivo phosphorus 31 nuclear magnetic resonance spectroscopy and by in vitro enzymatic analysis of frozen brain samples showed significant decreases in the level of phosphocreatine and relatively less change in ATP values. Progressive intracellular acidosis occurred, coincident with elevation of brain lactate concentrations. We conclude that the physiological and metabolic alterations that occur during prolonged seizures are not uniform, but change with time. Any hypothesis advanced to explain the mechanism of neuronal injury during prolonged seizures must take into account these temporally related changes. PMID- 4037748 TI - Evoked potential testing in relatives of multiple sclerosis patients. AB - Evoked potential (EP) tests were obtained in 110 neurologically normal first degree relatives of patients with multiple sclerosis. Visual EP tests were performed in all relatives; brainstem auditory and median nerve somatosensory EP tests were performed in 67 relatives. The relatives had a mean visual EP P100 latency that was significantly longer than that for normal subjects controlled for age and gender. Asymmetries were seen in results from individual MS relatives, including interocular visual EP P100 differences of up to 14 ms, and interarm somatosensory Erb-N18 differences of up to 3.0 ms. We identified 19 pairs of patients and relatives who were HLA identical and 18 other pairs who were HLA double nonmatched. EP asymmetries were seen more often in the HLA identical siblings than in the HLA double patients, especially if they share HLA types with the patients. Since less than 2% of siblings of MS patients would be expected to eventually develop clinical MS, these small subclinical electrophysiological changes are not expected to be a sign of the future appearance of clinical MS. Clinicians should be aware not to overinterpret small EP changes in relatives of MS patients. PMID- 4037749 TI - Pharmacokinetics of trihexyphenidyl after short-term and long-term administration to dystonic patients. AB - Although trihexyphenidyl has been used effectively for many years in the treatment of Parkinson's disease, little is known about its pharmacokinetics. Using a sensitive radioreceptor assay for anticholinergic drugs, we assayed trihexyphenidyl in human serum and studied its pharmacokinetics following short term and long-term administration to patients with dystonia. Previously untreated patients had a biphasic semilogarithmic plot of serum concentration-time consisting of an initial rapid distribution phase and a later slower elimination phase. Patients on long-term treatment showed only the slower elimination phase. Elimination followed first-order kinetics and was rapid, with a half-life of 3.7 +/- 0.4 (SEM) hours. There was no relationship between half-life and peak serum level, age, duration of therapy, or etiology or severity of dystonia. Although acute anticholinergic side effects paralleled the rise and fall of serum anticholinergic levels, the response of dystonia did not. PMID- 4037750 TI - Decreased sympathetic neuronal uptake in idiopathic orthostatic hypotension. AB - The disappearance rates from plasma of intravenously administered levo norepinephrine (l-NE), dextro-norepinephrine (d-NE), and isoproterenol (ISO) were measured in normal subjects and in patients with either multiple-system atrophy (MSA) or idiopathic orthostatic hypotension (IOH). The two isomers, l-NE and d NE, were removed at similar rates in all groups. In normal subjects, the d and l isomers of norepinephrine were cleared more rapidly than ISO. In patients with IOH, the initial rates of disappearance of the NE isomers from plasma were slower than normal and similar to the rate for ISO disappearance. Plasma NE levels, NE clearance, and the apparent release rate of NE into plasma from sympathetic neurons were significantly lower in patients with IOH than in normal subjects. Only the apparent NE secretion rate was related to the baseline plasma NE level. Sympathetic neuronal dysfunction in IOH is attended by a reduction in the clearance of NE. The very low plasma NE levels, in association with the striking reduction in NE clearance, suggest that in IOH there is a marked decrease in NE release. NE clearance and apparent NE secretion rate are normal in MSA, consistent with a central nervous system dysfunction in regulating the sympathetic nervous system. Neuronal uptake of NE in humans does not appear to be stereoselective. PMID- 4037751 TI - Leukoencephalopathy in diffuse hemorrhagic cerebral amyloid angiopathy. AB - We have studied 12 patients with diffuse hemorrhagic cerebral amyloid angiopathy clinically and at postmortem examination. The brains in 8 patients had diffuse bilateral loss of myelin in the hemispheric white matter sparing the U fibers, corpus callosum, and internal capsules. The periventricular areas were predominantly affected. Microscopic examination of the white matter showed an association with subacute or chronic edematous lesions: spongiosis, swollen oligodendroglia, widening of the perivascular spaces with edema fluid or siderophages, hyalinization of the blood vessel walls, incomplete myelin loss, and astrocytic gliosis. Three of 8 autopsied patients had undergone computed tomographic examination, which showed bilateral hypodensity of the hemispheric white matter. The brains of 4 patients with illnesses of shorter duration showed only discrete but similar lesions in the centrum semiovale. These white matter changes are similar to those observed in Binswanger's subcortical encephalopathy. We suggest that a common mechanism of hypoperfusion of the distal white matter causes the leukoencephalopathy. PMID- 4037752 TI - Ganglioside patterns in amyotrophic lateral sclerosis brain regions. AB - In a search for evidence of biochemical disorders in regions of postmortem brain other than the motor cortex in amyotrophic lateral sclerosis (ALS), ganglioside patterns were also examined in the frontal, temporal, and parahippocampal gyrus cortex. In 21 ALS brains studied (20 sporadic, 1 familial), abnormal patterns were found in the frontal cortex (81%), temporal cortex (75%), motor cortex (70%), and parahippocampal gyrus cortex (71%). Patterns were established by measuring the percentage distribution of 12 ganglioside species. Two abnormal patterns were detected. One was based on low proportions of GD1b, GT1b, and GQ1b associated with high proportions of GM2 and GD3 (GM1, GD1a, GD2, and GT1a values were normal). The second abnormality was the appearance of Gx. Neither abnormality was seen in the 13 non-ALS control brains. The first, and predominant, abnormality was found in the frontal cortex in 14 brains, and the second was observed in 13 brains; 10 brains showed both abnormalities. These findings thus constitute evidence that the disease process in ALS extends beyond the motor cortex and involves neurons in several brain areas. PMID- 4037753 TI - Acute traumatic midbrain hemorrhage. AB - A syndrome resulting from traumatic midbrain hemorrhage is described in 5 patients, 3 of whom had intracranial pressure measurements and 2 of whom had pathological examinations. The major clinical signs, evident immediately after injury, are coma, dilated (4 to 8 mm diameter) pupils that are fixed to light and dark, diminished limb tone, and impaired horizontal eye movements. The hemorrhages are single and linear or oval-shaped in the midsagittal rostral midbrain, extending several millimeters bilaterally. The appearance of the hematoma may be delayed on computed tomographic scanning, but early abnormalities of wave V of the brainstem auditory evoked potentials aid in diagnosis. Pathological features suggest that secondary brainstem distortion occurred soon after injury, perhaps resulting from a transiently raised intracranial pressure, but shearing injuries caused by acceleration-deceleration forces were also found. PMID- 4037754 TI - Serum prolactin and cortisol levels in evaluation of pseudoepileptic seizures. AB - In 6 patients with epilepsy, a twofold increase in serum prolactin levels followed true epileptic seizures, but no significant change followed pseudoepileptic attacks in 6 other patients. Serum prolactin concentration is a useful biochemical marker to distinguish between epileptic and pseudoepileptic seizures. Serum cortisol levels also increased after epileptic seizures, but diurnal and individual variations render the cortisol level a less reliable indicator of such attacks. PMID- 4037755 TI - The clinical value of free phenytoin levels. AB - The relationship between total and free phenytoin levels and drug toxicity was studied in 80 patients. Twenty-four were taking phenytoin alone. Drug toxicity was assessed by a "blind" rater using an eight-point standardized scoring system. The mean free phenytoin fraction was 0.076 in patients taking phenytoin alone or phenytoin and carbamazepine and 0.11 in patients taking valproic acid (p less than 0.001). The free fraction did not change with the total level over the range tested (6.7 to 39.9 micrograms/ml total phenytoin). There was a strong correlation between free and total levels (r = 0.84). Both free (r = 0.59) and total (r = 0.49) phenytoin levels were positively correlated with the toxicity score. Only total phenytoin levels showed a weak positive correlation with decreasing seizure frequency. Our results suggest that routine free phenytoin level monitoring is not necessary in most clinical situations. PMID- 4037756 TI - Metachromatic leukodystrophy manifesting as a schizophrenic disorder: computed tomographic correlation. AB - A 32-year-old woman with a 12-year history of schizophrenia demonstrated symmetrical bifrontal and biparietal periventricular hypodensities on computed tomographic scan. Sural nerve biopsy and urine and leukocyte enzyme assay confirmed the diagnosis of metachromatic leukodystrophy. The computed tomographic correlate in an adult with metachromatic leukodystrophy in whom the psychiatric manifestations were the predominant clinical feature is described. PMID- 4037757 TI - Hip flexion-abduction to elicit asterixis in unresponsive patients. AB - Asterixis at the hip joints can be elicited by a simple diagnostic maneuver in which the hips are passively flexed and abducted about 60 to 90 degrees between the thighs. The test evoked asterixis in 8 of 10 patients who were stuporous or semicomatose because of hepatic encephalopathy. The asterixis seems to be provoked by the involuntary contraction of hip adductors against gravity. PMID- 4037758 TI - Human cutaneous mechanoreceptors during regeneration: physiology and interpretation. AB - Percutaneous microneurography was used to record activity from single cutaneous afferents reinnervating the glabrous skin of the hand. Recordings were obtained from 6 months to 10 years after complete transsection of the median and/or ulnar nerves with subsequent repair. Transitional properties in the discharge behavior and receptive field characteristics of regenerating afferents were detected during the early stages of regeneration, when axonal maturation was still in progress; these may contribute to the slow time course of sensory recovery. Properties of reinnervated receptors long after nerve repair, when regeneration can be considered complete, indicated a correlation between electrophysiological findings and the final state of clinical recovery. The insights into the neural basis of sensory deficits provided by single-unit microneurography are not yielded by conventional study of the compound action potentials. This technique reveals new information about the pathophysiological nature of peripheral nerve injury and leads to a reinterpretation of clinical deficits. PMID- 4037759 TI - Investigation of human mitochondrial myopathies by phosphorus magnetic resonance spectroscopy. AB - Abnormal mitochondria are an increasingly recognized cause of neuromuscular disease. We have used phosphorus magnetic resonance spectroscopy to monitor noninvasively the metabolism of high-energy phosphates and the intracellular pH of human skeletal muscle in vivo in 12 patients with mitochondrial myopathy. At rest, an abnormality could be demonstrated in 11 of 12 patients. Ten patients had evidence of a reduced muscle energy state with at least one of the following abnormalities: low phosphorylation potential, low phosphocreatine concentration, high adenosine diphosphate concentration, or high inorganic phosphate concentration. Two patients had abnormal resting muscle intracellular pH. In some patients phosphocreatine concentration decreased to low values during exercise despite limited work output. This was not accompanied by particularly severe intracellular acidosis. Evidence of impaired rephosphorylation of adenosine diphosphate to adenosine triphosphate during recovery from exercise was found in approximately half the patients. Phosphorus magnetic resonance spectroscopy is useful in the noninvasive diagnosis of mitochondrial myopathies and in defining the pathophysiological basis of these disorders. PMID- 4037760 TI - Localization of lead in rat peripheral nerve by electron microscopy. AB - Lead intoxication in rats reliably produces segmental demyelination. Following a single intravenous injection of radioactive lead, localization of tracer was observed sequentially by quantitative electron microscopical autoradiography. The animals injected had been on a lead-containing diet for 70 days; as a result, the blood-nerve barrier was broken down and demyelination was proceeding. Six hours after a single dose, the lead was localized to the endoneurial space of the peroneal nerve, and 72 hours later, to the myelin membrane. Lead may exert a direct effect on the membrane and alter its stability both by altering the lipid content of the membrane and by directly interfering with the lamellar structure. PMID- 4037761 TI - Volume depletion and natriuresis in patients with a ruptured intracranial aneurysm. AB - We studied the sodium balance and changes in plasma volume by an isotope dilution technique in the first week after an aneurysmal subarachnoid hemorrhage in 21 patients. In 11 of the patients, the plasma volume decreased by more than 10%. This was accompanied by a negative sodium balance and hyponatremia in 6 patients, a negative sodium balance without hyponatremia in 4 patients, and a positive sodium balance in 1 patient. Together with a decrease in plasma volume, blood urea nitrogen content increased and body weight decreased. Three patients developed hyponatremia without a decrease in plasma volume. Serum vasopressin was measured in 14 of the 21 patients. The values were elevated on admission and declined in the first week, regardless of the presence of hyponatremia. These findings indicate that natriuresis and hyponatremia in aneurysmal subarachnoid hemorrhage reflect salt wasting and not inappropriate secretion of antidiuretic hormone and that these changes should be corrected by fluid replacement rather than by fluid restriction. PMID- 4037762 TI - Leptomeningeal dissemination of primary central nervous system tumors of childhood. AB - Presymptomatic craniospinal radiation therapy improves the rate of survival for children with brain tumors, which frequently metastasize to the leptomeninges. Radiotherapy may cause neurological damage and should be used only in patients considered to be at highest risk for leptomeningeal dissemination (LMS) at either the time of initial diagnosis or onset of disease relapse. We reviewed 314 consecutive patients with brain tumors to determine the incidence, timing, and importance of LMS. LMS occurred in 60 (19%) children. LMS occurred before diagnosis in 30 patients, as the only site of relapse or simultaneously with local first disease recurrence in 17 patients, and after local disease recurrence in 13 patients. Children with primitive neuroectodermal tumors, anaplastic gliomas, and ependymomas most frequently had LMS. Patients with primitive neuroectodermal tumors and posterior fossa anaplastic gliomas frequently had LMS before diagnosis or at the onset of relapse, whereas patients with ependymomas had LMS after local disease relapse. Both myelography and cerebrospinal fluid cytological examination are required to diagnose LMS. PMID- 4037763 TI - Developmental dyslexia: four consecutive patients with cortical anomalies. AB - We report the neuroanatomical findings in 4 consecutively studied brains of men with developmental dyslexia. The patients, who ranged in age between 14 and 32 years, were diagnosed as dyslexic during life. Nonrighthandedness and several autoimmune and atopic illnesses were present in the personal and family histories. All brains showed developmental anomalies of the cerebral cortex. These consisted of neuronal ectopias and architectonic dysplasias located mainly in perisylvian regions and affecting predominantly the left hemisphere. Furthermore, all brains showed a deviation from the standard pattern of cerebral asymmetry characterized by symmetry of the planum temporale. The neuroanatomical findings in these 4 patients are discussed with reference to developmental cortical anomalies, cerebral asymmetries, reorganization of the brain after early lesions, and the association between learning disorders, left handedness, and diseases of the immune system. PMID- 4037764 TI - The clinical spectrum of necrotizing angiopathy of the peripheral nervous system. AB - The peripheral neuropathy seen with necrotizing angiopathy is said to begin classically as a mononeuritis multiplex, usually associated with polyarteritis nodosa, rheumatoid arthritis, or systemic lupus erythematosus. Our experience, however, suggests that a large number of these patients do not have a well defined collagen vascular disease or the typical clinical pattern. In 350 consecutive nerve biopsies (sural or superficial radial), 16 patients showed a necrotizing angiopathy in the epineurial blood vessels. Six of these 16 patients had a distal symmetrical sensorimotor polyneuropathy. The remaining 10 had a mononeuritis multiplex, although in 8 overlapping nerve involvement somewhat obscured the picture of mononeuritis. In 12 patients, no specific underlying collagen vascular disease could be diagnosed by accepted criteria despite extensive clinical, radiological, and serological evaluations. The peripheral neuropathy was the only objective evidence of vasculitis in 7 of these 12 patients. Our findings suggest that patients with a peripheral neuropathy secondary to necrotizing angiopathy often do not have a definable collagen vascular disease. In fact, peripheral neuropathy may be the sole manifestation of vasculitis. Furthermore, the neuropathy was found to be a distal symmetrical sensorimotor neuropathy in a higher proportion of cases than has been documented previously. PMID- 4037765 TI - Treatment of central nervous system sarcoidosis with radiotherapy. AB - This report documents the twelve-year follow-up of a patient with neurosarcoidosis with multiple progressive central nervous system manifestations. Increased somnolence and seizure activity were associated with proliferation of nodular enhancing brain lesions, as seen on serial computed tomographic (CT) scans. Initially he responded to corticosteroid treatment, but gradually this response became unsatisfactory. After whole-brain irradiation with a total dose of 3,000 rads, his clinical symptoms improved with disappearance of the enhancing brain lesions seen on CT scan. PMID- 4037766 TI - Isolated angiitis of the central nervous system. AB - Angiitis confined to the central nervous system is a rare disorder in which inflammation and consequent irregular narrowings of medium-sized cerebral arteries are prominent. Clinical and radiological features in 3 patients with this condition are described. All patients responded to either steroid or steroid plus azathioprine therapy. PMID- 4037767 TI - Self-abatement of complex partial seizures. AB - Seven of 71 patients with complex partial seizures claimed they were able to abate their seizures, while none of 18 with simple partial seizures were able to do so. Self-abatement exercises included highly stereotyped cognitive and physical components unique to the individual. Those who could abate their seizures had attained higher educational status, better social and vocational adjustment, and better psychological adjustment than did the control group of patients with epilepsy. The self-abatement group was also more likely to have right hemispheric electroencephalographic abnormalities. Characterization of the self-abatement group may be relevant to the selection of candidates for behavioral therapy for epilepsy. PMID- 4037768 TI - Hypertensive encephalopathy: diffuse reversible white matter CT abnormalities. PMID- 4037769 TI - Synergistic activity of combinations of recombinant human alpha interferon and acyclovir, administered concomitantly and in sequence, against a lethal herpes simplex virus type 1 infection in mice. AB - The nucleoside analog acyclovir [9-(2-hydroxyethoxymethyl)guanine] and the hybrid recombinant human alpha interferon (rHuIFN-alpha A/D) were evaluated in weanling mice for their efficacy alone and in combination against a lethal systemic infection with herpes simplex virus type 1. Simultaneous parenteral treatment with combinations of both agents at various doses resulted in a higher percentage of survival than when either agent was administered alone, with a synergistic interaction demonstrated at certain dose combinations. Sequential administration of parenteral rHuIFN-alpha A/D and oral acyclovir, administered by gavage or supplied ad libitum in drinking water, resulted in a synergistic interaction at all dose combinations tested. These results suggest that combinations of interferon and acyclovir may be useful in treating primary herpes simplex virus infections in humans. PMID- 4037770 TI - Comparison of topically applied 5-ethyl-2'-deoxyuridine and acyclovir in the treatment of cutaneous herpes simplex virus infection in guinea pigs. AB - Three percent 5-ethyl-2'-deoxyuridine (EdU) in an aqueous cream base was compared with 5% acyclovir (ACV) in polyethylene glycol ointment and 3% EdU in 95% dimethyl sulfoxide (DMSO) for efficacy in the topical treatment of an experimental dorsal cutaneous herpes simplex virus type 1 infection in guinea pigs. Topical ACV treatment reduced the mean lesion number by 15%, the lesion area by 32%, and the lesion virus titer by 60% when compared with measurements at contralateral sites treated with the vehicle alone. Application of 3% EdU cream was more beneficial, effecting reductions of 29, 44, and 68% in the same measurements. EdU in DMSO was even more effective, reducing the lesion measurements by 39, 60, and 90%, respectively. The penetration of EdU and ACV through guinea pig skin was compared in single-chamber diffusion cells. In the aqueous cream, EdU readily penetrated excised skin and exhibited rates of flux 10 fold greater than those shown by ACV in ointment formulation (0.56 versus 0.05 microgram/cm2 per h; P = 0.05). The flux of EdU in DMSO was 3.39 micrograms/cm2 per h, six times higher than the flux in the cream vehicle. EdU was more effective than ACV in this experimental animal model, most likely due to better percutaneous drug delivery of EdU from the cream and DMSO vehicles. PMID- 4037772 TI - Cefotaxime diffusion into cerebrospinal fluid of children with meningitis. AB - Cefotaxime diffused consistently and in therapeutic levels into the cerebrospinal fluid (CSF) of 13 children successfully treated for bacterial meningitis. CSF cefotaxime levels early (6.0 micrograms/ml) and late (1.2 micrograms/ml) in treatment were severalfold the MBCs for the infecting organisms. After a single 40-mg/kg dose to each of five infants with ventriculostomies, mean CSF levels of cefotaxime were 6.4, 5.7, and 4.5 micrograms/ml at 2, 4, and 6 h, respectively. PMID- 4037771 TI - Difference in blister fluid penetration after single and multiple doses of ceftriaxone. AB - Plasma and suction skin blister fluid concentrations of ceftriaxone were studied in 12 subjects after intravenous administration of 1 g of ceftriaxone every 12 h (q12h) and 2 g every 24 h (q24h) after single and multiple doses. Ceftriaxone concentrations were determined by high-pressure liquid chromatography. Mean peak plasma concentrations (at the end of the 5-min infusion) were 254.0 and 374.8 micrograms/ml after administration of 1 g q12h after single and multiple doses, respectively. Similarly, with 2 g q24h, maximum levels were 409.6 and 443.5 micrograms/ml. Forty-eight hours after the last dose of ceftriaxone, plasma concentrations were still detectable: 1.2 micrograms/ml after 1 g q12h and 3.0 micrograms/ml after 2 g q24h. Higher ceftriaxone concentrations were observed in blister fluid after multiple doses than after a single dose. Peak concentrations almost doubled in the blister fluid after multiple doses: 36.0 versus 67.0 micrograms/ml and 38.6 versus 68.9 micrograms/ml for 1 g q12h and 2 g q24h, respectively. Elimination half-life of ceftriaxone in the blister (8.3 and 11.5 h) was longer than plasma half-life (6.3 h). With the area under the concentration-time curve ratio, a 113% increase in tissue penetration was observed after multiple doses for the 1 g q12h regimen. The free plasma and blister fluid ceftriaxone concentrations observed at the end of the dosing interval of the 2 g q24h regimen were higher than the MIC for 90% of the susceptible microorganisms and justified the once-a-day use of ceftriaxone. PMID- 4037773 TI - Effects of elevation of serum cholesterol and administration of amphotericin B complexed to lipoproteins on amphotericin B-induced toxicity in rabbits. AB - Amphotericin B was infused into normal rabbits or rabbits made hypercholesterolemic by diet. There was no difference in amphotericin B-induced toxicity between these two groups. Amphotericin B given in a mixture with human low-density lipoproteins was more toxic than when given without lipoproteins. PMID- 4037774 TI - Pharmacokinetic evaluation of cefoperazone in infants. AB - The pharmacokinetics of cefoperazone were evaluated in 25 infants (mean age, 26 days) after intramuscular and intravenous routes of administration. The levels in blood that were achieved were severalfold higher than those required to inhibit common pathogens. The mean half-life of 240 min was one-half of that observed in 1- to 2-day-old infants but about twice that seen in adults. Further evaluation is needed to study the efficacy of the drug in infants and children. PMID- 4037775 TI - In vitro susceptibilities of Aeromonas hydrophila, Aeromonas sobria, and Aeromonas caviae to 22 antimicrobial agents. AB - MICs of 22 antimicrobial agents for 60 strains of three Aeromonas species were determined by a microdilution method. The newer cephalosporins such as moxalactam, cefotaxime, and cefoperazone, the aminoglycosides, and chloramphenicol, tetracycline, nitrofurantoin, and trimethoprim-sulfamethoxazole inhibited most of the strains studied. Within the genus, A. hydrophila was more resistant than either A. caviae or A. sobria to the antibiotics tested. PMID- 4037776 TI - Specific inhibition of spermidine synthesis in Mycobacteria spp. by the dextro isomer of ethambutol. AB - Only the dextro isomer of ethambutol inhibited mycobacterial spermidine synthase and spermidine biosynthesis. Inhibition of mycobacterial spermidine synthase appeared to be specific. Spermidine synthase from Mycobacterium fortuitum, which was resistant to ethambutol in vitro, required a higher concentration of ethambutol for its inhibition than the enzyme of susceptible Mycobacterium bovis. PMID- 4037777 TI - Pharmacokinetics of intravenous amdinocillin in healthy subjects and patients with renal insufficiency. AB - Five healthy volunteers and 31 patients with various degrees of renal impairment received a 10-mg/kg intravenous dose of amdinocillin by infusion over 15 min to establish the disposition profile of the drug in plasma and urine. Both clearance from plasma and elimination rate constant showed a linear relationship with creatinine clearance. It was noted that in subjects with creatinine clearances of greater than 50 ml/min, the elimination half-life remained relatively constant; however, as the creatinine clearance decreased from 50 to 5 ml/min, there was a progressive rise in the elimination half-life. Despite the removal of the drug by hemodialysis (32 to 72% of the dose), concentrations of amdinocillin in plasma remained in the therapeutic range. In patients undergoing peritoneal dialysis, less than 4.0% of the infused dose was removed by dialysis during the hourly exchanges over a 14- to 18-h period. Although the clearance from plasma and the half-life of amdinocillin were altered up to fourfold in patients with creatinine clearances of less than 15 ml/min, the amdinocillin dosage per se may not need to be reduced for these patients if the frequency of dosing is reduced from six to three or four times daily. This is based on drug accumulation estimates of 56% from a regimen of 10 mg/kg every 8 h in these patients as compared with less than 10% from a regimen of 10 mg/kg every 4 h in subjects with normal renal function. In addition, supplemental doses may not be necessary during or at the end of hemodialysis for patients undergoing hemodialysis. PMID- 4037778 TI - Reisolation of Ruminobacter parvum. AB - A cellulolytic gram-negative ovoid motile rod (strain GS III) was isolated from an in vitro incubation of ground barley straw in rumen fluid. The anaerobic, non sporulating, mesophilic organism strongly answered the original description of Ruminobacter parvum (Kaars Sijpesteijn, 1948). The strain GS III fermented pyruvate, D-arabinose, D-xylose, cellobiose, sucrose, maltose, cellulose, dextrin, xylan and pectin. Products from cellobiose were D-lactate, ethanol, acetate, hydrogen and carbon dioxide. A heat-resistant factor in yeast extract that was not a B-vitamin, a metal or one of the volatile fatty acids was required for growth. The mol % G + C was 51.9. The organism was lost after prolonged subculture. PMID- 4037779 TI - Production, purification and partial characterization of an endo polygalacturonase from Cryptococcus albidus var. albidus. AB - Cryptococcus albidus var. albidus produced an extracellular endo polygalacturonase (poly (1,4-alpha-D-galacturonide) glycanohydrolase EC 3.2.1.15) when grown in a synthetic medium containing one of a variety of pectic substances or galacturonic acid. The highest level of enzyme activity (15.5 VU X ml-1) was obtained after 72 h of growth on 1.0% low-methoxyl pectin. The enzyme, purified by gel filtration (Sephadex G-100) after repeated ammonium sulphate precipitation and dialysis, showed only one band by polyacrylamide gel electrophoresis and had the following properties: mol wt (MWr) 41000 dal; isoelectric point (pI) = 8.10 +/- 0.10; optimum temperature and pH for activity around 37 degrees C and pH 3.75, respectively; pH stability in the pH range 4.0 to 8.0; complete heat inactivation after 10 min at 55 degrees C; Km and Vmax values 5.7 X 10(-1) mg X ml-1 and 5.1 X 10(-1) mmoles X min-1, respectively. PMID- 4037780 TI - Conspecificity of Hanseniaspora nodinigri and Hanseniaspora vineae: comparison by DNA reassociation. AB - Hanseniaspora nodinigri Lachance 1981, found in black knots (caused by Dibotryon morbosum) of Prunus virginiana, was described as a new species, some time after publication of the extensive study by Meyer et al. (1978) on the systematics of Hanseniaspora Zikes and its imperfect counterpart Kloeckera Janke. Lachance delimited the species from other members of the genus because of absence of growth on glucono-delta-lactone. He also stated that this species, although evidently similar in many ways to H. vineae van der Walt et Tscheuschner and H. osmophila (Niehaus) Phaff et al., has 'diverged from them, possibly in its adaptation to growth in association with black knots'. PMID- 4037781 TI - Temperature-dependent lipid content and fatty acid composition of three thermophilic bacteria. AB - The lipid content and fatty acid composition of a strain of Bacillus caldolyticus and of two facultative thermophiles (B. flavothermus and strain NZ-2) were analysed after growth at different temperatures. In all three strains the amount of membrane, as a fraction of total cellular dry mass, was found to increase with temperature, however, in varying degrees. Changes of lipid content and protein/lipid ratio in B. caldolyticus between 60 degrees C and 100 degrees C and in strain NZ-2 between 45 degrees C and 70 degrees C were minor; in B. flavothermus the alterations in the 50 degrees C-70 degrees C range were more pronounced. The same was found for changes observed in the phospholipid/total lipid and phospholipid/membrane ratios, and also in the amounts of individual phospholipids. The alterations of the fatty acid composition were most significant in B. caldolyticus, especially between 80 degrees C and 95 degrees C. In contrast, the main changes in B. flavothermus and NZ-2 were found to occur between 30 degrees C and 50 degrees C, and between 45 degrees C and 60 degrees C, respectively. Based on these data, strain NZ-2 could be characterized as the least and B. flavothermus as the most versatile of the three organisms. PMID- 4037782 TI - Improvement of sporulation in the yeast Yarrowia lipolytica. AB - Strains of Yarrowia lipolytica forming exclusively spherical ascospores were developed through inbreeding. These strains are more suitable for micromanipulation than other inbred strains forming helm-shaped ascospores. External factors affecting sporulation frequency and tetrad formation in this yeast were investigated. Optimal formation of complete tetrads occurred at a narrow range of pH values around 6.0. Citrate was found to stimulate sporulation strongly. A synthetic medium containing citrate was developed to obtain standard conditions for maximum sporulation. PMID- 4037783 TI - Thermostability of enzymes of the tricarboxylic acid cycle of Bacillus coagulans. AB - The thermostability of four enzymes of the tricarboxylic acid cycle has been studied in the facultative thermophile, Bacillus coagulans. Although isocitrate dehydrogenase appeared to be more temperature-sensitive in whole-cell extracts of cultures grown at 30 degrees C compared with that in cultures grown at 55 degrees C, this difference could be largely eliminated by the removal of cell-wall material. The specific activity of each of the enzymes examined was approximately threefold higher in cultures grown at 55 degrees C than in those grown at 30 degrees C. The maximum temperature, Arrhenius plot and effect of stabilizing agents for each enzyme were examined and found to be independent of growth temperature. Sodium chloride (10% w/v) was an effective protective agent for fumarase, aconitase and malate dehydrogenase. Protection from thermal denaturation of isocitrate dehydrogenase, aconitase and fumarase but not malate dehydrogenase was also given when the enzymes were heated in the presence of their substrates. These results are discussed in light of the generalized theories of facultative thermophily which have been proposed. PMID- 4037784 TI - Plasmid-determined cloacin DF13-susceptibility in Enterobacter cloacae and Klebsiella edwardsii; identification of the cloacin DF13/aerobactin outer membrane receptor proteins. AB - Both Enterobacter cloacae H478 and Klebsiella edwardsii S15 were shown to harbour a relatively large conjugative plasmid that coded for cloacin DF13-susceptibility and the production and uptake of a hydroxamate iron chelator, most probably aerobactin. Protein-blotting experiments with antiserum raised against the purified cloacin DF13/aerobactin receptor protein from Escherichia coli (Co1V K30) revealed that the corresponding outer membrane receptor proteins of Ent. cloacae H478 and K. edwardsii S15 had apparent mol wts of 85 000 and 76 000, respectively. E. coli transconjugants harbouring either the plasmid from Ent. cloacae H478 or K. edwardsii S15 expressed a cloacin DF13/aerobactin outer membrane receptor protein with a mol wt of 74 000. The receptor protein encoded by the Ent. cloacae and K. edwardsii plasmids were immunologically more related to each other than to the pCo1V-K30-encoded receptor protein. PMID- 4037785 TI - Fish flesh agar medium--a suitable experimental medium for the detection of spoilage bacteria. AB - The spoilage characteristics of bacterial strains were studied by growing them at 28 +/- 2 degrees C in agar and broth media prepared with sterile fish and prawn flesh homogenates. The percentage of spoilers found among the bacterial isolates tested, as shown by odour production and halo zone formation, was independent of the source of flesh used. Indole and fluorescent pigment production were also observed in the broth. Pseudomonas, Vibrio and Acinetobacter exhibited faster growth in flesh media than in the usual artificial media. Decrease of protein and lipid concentration in the clear zone of agar media suggests the utilization of the available substrate by spoilage bacteria. PMID- 4037786 TI - Influence of self-monitoring on heterosexual conversational behaviors of head trauma youth. AB - This study evaluates the impact of self-monitoring on three heterosexual conversational behaviors of head trauma youths. Two 5-minute audiotaped conversations occurred daily between the youths and unfamiliar female confederates. Two conversations occurring on alternate days in clinical and natural conversational settings were scored for the frequency of compliments, questions, and self-disclosures. A multiple baseline analysis with alternating treatments for "instructions to self-monitor" and "no instructions to self monitor" revealed (a) self-monitoring had an accelerative effect on compliments and questions and a decelerative effect on self-disclosure; (b) self-monitoring effects were maintained despite transferring from a mechanical counter to an unspecified covert monitoring procedure; (c) self-monitoring had a comparable effect whether employed in a clinical or functional communication setting; (d) performance of the target behavior was most strongly influenced under the "instructions to self-monitor condition;" (e) once intervention was directed to another response, the rate under the instructions and no instruction conditions became equivalent; and (f) the results maintained over a 1-month follow-up for one youth available for observation. Finally, social comparison and subjective evaluation data supported the importance of intervention. PMID- 4037787 TI - Effects of delayed versus immediate attention to oral reading errors on the reading proficiency of mentally retarded children. AB - The impact of two variations of teacher attention to oral reading errors and a no treatment control condition were compared in an alternating treatments design. For four moderately mentally retarded children, each uncorrected oral reading error was followed by: (a) immediate teacher attention, with the teacher correcting the error word as soon as it occurred, (b) delayed teacher attention, with the teacher correcting the error word at the end of the sentence in which it occurred or within 10 to 15 seconds if the subject paused following an error, or (c) no teacher attention. Both immediate and delayed teacher attention were effective in reducing the number of uncorrected oral reading errors and increasing the number of self-corrections when compared to the no-treatment control. However, the delayed condition had greater effect than the immediate condition on both measures. In a later remediation phase, when only the delayed treatment was given, uncorrected errors remained at low levels whereas self corrections generally increased. Total errors, whether subsequently self corrected or not, with one exception, decreased during the study. PMID- 4037788 TI - Depression and learned helplessness in mentally retarded and nonmentally retarded adolescents: an initial investigation. AB - Depression and learned helplessness were examined in a sample of 26 educably mentally retarded (EMR) adolescents and a matched (on age, sex, and race) group of 26 nonmentally retarded adolescents. Depression and learned helplessness were assessed using the Reynolds Adolescent Depression Scale (RADS) and Mastery Orientation Inventory (MOI), respectively. Results indicated that EMR adolescents manifested significantly (p less than .001) greater depressive symptomatology than their nonmentally retarded peers. Sex differences were also found, with females demonstrating greater depression scores in both groups. Analysis of severity of symptom endorsement showed significant group differences on items reflecting somatic, self-evaluative, and behavioral components of depression, with mentally retarded subjects demonstrating higher scores. Mentally retarded adolescents were found to score higher (p less than .001) on the learned helplessness measure than nonmentally retarded adolescents. Given the problematic nature of depression noted in large sample epidemiological studies of nonmentally retarded adolescents, the results of this investigation indicate that depression in EMR adolescents is an affective characteristic in need of further study. PMID- 4037789 TI - Systematic assessment and training of sex education for a mentally retarded woman. AB - A systematic sex education program was implemented to provide the instruction necessary for a mentally retarded woman to be able to label basic reproductive body parts and describe and demonstrate a breast examination, Pap test, and pelvic examination. The training program permitted documentation of informed consent for a reproductive health examination. Training was implemented in a multiple probe design across skill areas and consisted of providing factual information, requiring the subject to repeat factual information, using concrete teaching aids, demonstrating examination procedures, requiring the subject to demonstrate the specified examinations, and providing praise for correct responses. Results showed dramatic increases in sexual knowledge with the implementation of the program. Follow-up data indicated that the increase in sexual knowledge was maintained over a period of 3 weeks. PMID- 4037790 TI - Attention to multiple cues by severely mentally retarded adults: effects of single-component pretraining. AB - The present investigation examined whether the amount of compatible single element training affected response accuracy for conditional-discrimination tasks requiring attention to multiple cues. Four severely mentally retarded adults participated, and a multiple baseline across subjects and reversal design was employed. Following acquisition of conditional discriminations by individually training each stimulus element, transfer tests were provided. In the first transfer condition, two intermixed conditional-discrimination tasks were presented containing identical stimuli to those individually trained. The second transfer condition consisted of two intermixed conditional-discrimination tasks composed of novel S- stimuli and pretrained S+ stimuli. Finally, a control procedure was administered in which conditional-discrimination tasks contained all untrained cues. The severely mentally retarded subjects did learn to respond to multiple cues. Establishing separate control by each component produced attention to two aspects of compound stimuli with few errors occurring. In addition, these broadened attentional skills generalized to multistimulus tasks containing all or some of the original pretrained stimuli. If single-element training was omitted, performance on conditional-discrimination tasks was greatly impaired. PMID- 4037791 TI - Self-management training of mentally retarded adults presenting severe conduct difficulties. AB - Chronic and clinically significant conduct difficulties of mildly and moderately mentally retarded adults in a vocational setting were reduced with a multicomponent self-management package. Skills of self-monitoring, self evaluation, self-consequation, and self-instruction were trained and practiced in vivo. Positive effects on behaviors not specifically treated also were noted for some subjects. A combined treatment withdrawal and multiple baseline design was used to assess changes. Nine-month follow-up under different work conditions revealed continued maintenance of treatment gains. PMID- 4037792 TI - Functions of haptic perceptual activity in persons with visual and developmental disabilities. AB - The paper reviews the author's research on the effects of perceptual experience and cognitive-developmental factors on haptic scanning behavior of blind and/or mentally retarded children and adults. The results indicate that haptic information may be gathered more efficiently by one scanning style over another, and differences in efficient style usage may vary positively with haptic perceptual experience. However, accurate processing of haptic information may depend on the availability of cognitive structures that in turn influence scanning style selection and utilization, rather than directly on scanning styles themselves. PMID- 4037793 TI - The impact of deinstitutionalization on activities and skills of severely/profoundly mentally retarded multiply-handicapped adults. AB - This study evaluated the change in activity patterns and skills of severely/profoundly mentally retarded, multiply-handicapped residents as they moved from large total care institutions to community living. Twenty-seven individuals were evaluated just before leaving the institution, 3 months post exit, and 9 months post-exit. In comparison to a nondisabled reference group, residents were less active, mobile, social, and independent both in the institution and community. Residents did show, however, significant changes toward the nondisabled pattern of daily living after moving to the community. Clients improved in 4 of 16 skill areas within 3 months after entering the community: expressive communication, eating, serving meals and washing dishes, and meal preparation. PMID- 4037794 TI - Modulation of platelet-activating factor (PAF) synthesis and release from human polymorphonuclear leukocytes (PMN): role of extracellular albumin. AB - Human neutrophilic polymorphonuclear leukocytes (PMN) stimulated with N'-formyl methionyl-leucyl-phenylalanine (FMLP) in the presence of cytochalasin B but in the absence of human serum albumin (HSA) synthesized only small amounts of platelet-activating factor (PAF) that attained maximum levels within 60-120 s after stimulation; in addition, no release of PAF occurred. However, in the presence of 2.5 mg HSA/ml, there was a threefold increase in PAF synthesis, 30 40% of which was released within 5 min after FMLP stimulation. In the presence of 50 mg HSA/ml there was at least a fourfold increase in PAF synthesis and release, with maximal synthesis occurring 10-20 min after stimulation. Thus, the presence of HSA during PMN stimulation not only induced an albumin dose-dependent increase in PAF release but significantly augmented the synthesis of PAF. In contrast to PAF synthesis and release, the presence or absence of HSA had no effect upon lysosomal enzyme secretion from FMLP-stimulated PMN, which was maximal within 30 60s after stimulation. These results demonstrate that HSA plays an essential role in vitro in the synthesis and release of PAF from human PMN, and support the hypothesis that there is a cyclic PAF synthesis-release coupling mechanism in the stimulated human PMN. PMID- 4037795 TI - Purification and partial sequencing of bovine liver alkaline phosphatase. AB - Bovine liver alkaline phosphatase has been purified to homogeneity by procedures that include reverse-phase HPLC. The pure enzyme has an apparent Mr of 160,000 and is composed of what appears to be two identical monomers of Mr 82,000. About 80% of the material yielded the amino-terminal sequence Leu-Val-Pro-Glu-Lys-Glu Lys-Asp-Pro-?-Tyr-?-Arg-Asp-Gln-Ala-Gln. The minor component was extended at the amino terminus by two residues that have not yet been identified, i.e., ?-?-Leu Val-Pro-Glu-Lys-Glu-Lys-Asp-Pro-?-Tyr-?-Arg-Asp-Gln-Ala-Gln. PMID- 4037796 TI - Cytochrome P-450 ligands: metyrapone revisited. AB - Expressing metyrapone interactions with ferrous cytochrome P-450 as ligand saturation by cytochrome, rather than the more conventional cytochrome saturation by ligand, an extinction coefficient of 68.5 +/- 1.8 mM-1 cm-1 for the metyrapone complex of dithionite-reduced rat hepatic microsomal cytochrome P-450 was derived. Utilizing this new extinction coefficient, the increased cytochrome P 450 present after phenobarbital induction was almost exclusively that which is able to both bind to metyrapone and form a metabolic-intermediate complex from norbenzphetamine. However, it was not the only subpopulation present in microsomes that was able to bind metyrapone, nor the only one capable of forming a metabolic intermediate complex from norbenzphetamine. Thus, neither technique alone can be used to quantitate the "phenobarbital-induced form" of cytochrome P 450. PMID- 4037797 TI - Purification and partial characterization of ceruloplasmin from chicken serum. AB - The preparation and properties of ceruloplasmin from chicken serum are described. Ethanol-CHCl3 was used to precipitate the crude protein, followed by adsorption and elution from DEAE-Sephadex. Further treatment with Sephadex G-200 and CM Sephadex yielded an intensely blue protein judged 1572-fold purer than starting serum. epsilon-Aminocaproic acid (0.02 M) was present in all buffers and starting sera. Chicken ceruloplasmin appears to be a single polypeptide, apparent Mr 124,000, with an A610/A280 ratio of 0.07 and an absorption maximum at 602 nm. Hexose, hexosamine, and sialic acid accounted for 7.2% of the weight; copper represented 0.20%, which suggested four or five copper atoms per molecule. Chicken ceruloplasmin catalyzed the azide-sensitive oxidation of p phenylenediamine (PPD) and N,N'-dimethyl-p-phenylenediamine (DPD), and showed ferroxidase activity similar to that of human ceruloplasmin. Its amino acid composition, although similar in many residues to human ceruloplasmin, was decidedly lower in methionine and tyrosine. The chicken protein had one-third the sialic acid content of human ceruloplasmin and showed immunochemical nonidentity with human ceruloplasmin. PMID- 4037798 TI - Elicitor induction of a microsomal 5-O-(4-coumaroyl)shikimate 3'-hydroxylase in parsley cell suspension cultures. AB - Microsomal preparations from parsley cell suspension cultures challenged with an elicitor from Phytophthora megasperma f.sp. glycinea (Pmg) catalyze the formation of trans-5-O-caffeoylshikimate from trans-5-O-(4-coumaroyl)shikimate. Neither the cis isomer nor free 4-coumarate, 4-coumaroyl-CoA, or 5-O-(4-coumaroyl)quinate are substrates for this enzyme. The reaction is strictly dependent on NADPH as a reducing cofactor and on molecular oxygen. NADH, ascorbic acid, and 6,7-dimethyl 5,6,7,8-tetrahydropterine cannot substitute for NADPH. However, NADH enhances enzyme activity observed in the presence of NADPH. Cytochrome c and carbon monoxide inhibit the hydroxylation reaction, suggesting a cytochrome P-450 dependent mixed-function monooxygenase. PMID- 4037799 TI - A comparison of the effects of cyanide, hydrogen peroxide, and phenylglyoxal on eucaryotic and procaryotic Cu,Zn superoxide dismutases. AB - The Cu,Zn superoxide dismutases from bovine liver, yeast, Caulobacter crescentus, and Photobacter leiognathi were compared for their susceptibilities to inhibition by cyanide and to inactivation by hydrogen peroxide and phenylglyoxal. All of these enzymes were affected by these reagents, albeit with some differences in sensitivity. The yeast and the bacterial enzymes were thus more sensitive to cyanide than was the bovine enzyme, while the bovine and the yeast enzymes were inactivated more rapidly by hydrogen peroxide and less rapidly by phenylglyoxal than were their bacterial counterparts. The qualitative similarities in the behavior of all of these enzymes suggest overriding similarities in their active site regions. However, a quantitative comparison of the data suggests that the bacterial enzymes are more like each other than they are like the eucaryotic enzymes, and furthermore, are more like the yeast enzyme than the bovine enzyme. PMID- 4037800 TI - Study of bilirubin metabolism by high-performance liquid chromatography: stability of bilirubin glucuronides. AB - The stabilities of bilirubin (BR) glucuronide, monoglucuronide (BMG), and diglucuronide (BDG) were studied under various conditions by HPLC. In aqueous media, BMG showed a pronounced lability and was easily transformed into equimolar BDG and BR. It was proved by direct analysis of tetrapyrrole isomers that BDG and BR were formed from dipyrrole exchange of BMG molecules. All reducing agents examined (sodium ascorbate, cysteine, GSH, dithiothreitol, NADH, and NADPH) suppressed the transformation of BMG into BDG and BR. Bovine serum albumin and rat liver cytosol fractions also stabilized BMG strongly. BDG was fairly stable in aqueous media as compared with BMG. When BMG was incubated both with and without liver plasma membranes (N2 fraction) from Wistar rats, the formation rates of BDG and BR in both incubation mixtures were exactly the same. The composition of BDG and BR isomers was the same in both mixtures. Also, heat denaturation of the plasma membranes did not affect formation rates. Moreover, the reaction was completely inhibited by sodium ascorbate. These findings indicate that rat liver plasma membranes have no enzyme activity for BDG formation from BMG. PMID- 4037801 TI - Synthesis and degradation of 3-methylcholanthrene-inducible cytochromes P-450 and their mRNAs in primary monolayer cultures of adult rat hepatocytes. AB - We used primary nonproliferating cultures of adult rat hepatocytes to investigate the regulation of P-450c and P-450d, immunochemically related protein products of separate cytochromes P-450 genes that are coinduced by 3-methylcholanthrene and related compounds. In cultures of hepatocytes prepared from untreated rats and incubated in media containing 3-methylcholanthrene, beta-naphthoflavone, 3,4,3',4'-tetrachlorobiphenyl, and Aroclor 1254 (a mixture of chlorinated biphenyls) there was a 5- to 15-fold accumulation of P-450c protein (quantitated by immunoblotting), accompanied by an increased rate of P-450c synthesis (measured as incorporation of [3H]leucine into immunoprecipitable protein) and an increased amount of P-450c mRNA hybridizable to a specific cloned cDNA (p210). In contrast, there were no increases in the concentration of P-450d protein, its rate of synthesis, or the amount of P-450d mRNA hybridizable to its specific cDNA (p72). Similarly, when "preinduced" hepatocytes (isolated from rats treated with Aroclor 1254) were incubated for 4 days in culture medium, the amount of P-450c, its rate of synthesis, and the amount of P-450c mRNA remained elevated, whereas synthesis of P-450d and the amount of P-450d mRNA fell precipitously to less than 10% of the initial values despite the presence or absence of Aroclor 1254 or of isosafrole in the medium. However, the loss of P-450d protein in these cultures was almost completely prevented when isosafrole was added to the culture medium and was partially prevented when safrole, Aroclor 1254, and 3,4,5,2',4',5' hexachlorobiphenyl, but not 3-methylcholanthrene, beta-naphthoflavone, or 3,4,3'4'-tetrachlorobiphenyl, were in the culture medium. Moreover, in similar cultures of "preinduced" hepatocytes that were pulse-labeled with [3H]leucine, the presence of isosafrole in the culture medium extended the apparent half-life for loss of radioactivity in immunoprecipitable P-450d to a value of 72 h (3-fold longer than in standard medium) but was without effect on the rate of disappearance of radiolabeled P-450c. We conclude that control of P-450d degradation is an important factor in the regulation of this hemoprotein and that induction of P-450c and P-450d proceed by separate pathways that are spontaneously divorced under standard conditions for primary culture of adult rat hepatocytes. PMID- 4037803 TI - Reconciliation of the absorption change at 325 nm and other flash-yield determinations of concentrations of active photosystem II centers. AB - The concentration of photosystem II was determined in thylakoids of dwarf peas by the use of the following methods: absorption change at 325 nm; atrazine binding; and flash yields of oxygen evolution (Emerson-Arnold method), of protons from oxidation of water, and of reduction of DCIP. For the first time all of the flash yield measurements have been done on the same sample and give equivalent values for the concentration of photosystem II. Agreement of the absorption change measurement at 325 nm with the other measurements was accomplished by the introduction of important improvements to the methods of Melis and co-workers [Proc. Natl. Acad. Sci. USA (1980) 77, 4712-4716]. The atrazine-binding method gave photosystem II values that were twice as large as any of the other photosystem II measurements. Possible reasons are discussed for this discrepancy in terms of the secondary acceptor (Q400) of Ikegami and Katoh [Plant Cell Physiol. (1973) 14, 829-836]. The concentration of photosystem I was measured by absorption change at 705 nm. From the concentration values of photosystem II and I the system II/I stoichiometry was calculated. PMID- 4037802 TI - Electron microscopy of seed-storage globulins. AB - The quaternary structures of a range of seed globulins, including examples of both the so-called 7 S and 11 S types, have been examined by electron microscopy. The legume 7 S proteins, phaseolin (bean), beta-conglycinin (soybean), and vicilin (pea), appear as flat discs of diameter ca. 8.5 nm and thickness ca. 3.5 nm formed by association of three subunit domains. Phaseolin converts to an 18 S tetramer at acid pH, and images recorded under these conditions suggest that four of the 7 S protomer discs associate to form the faces of a regular tetrahedron. The classical 11 S seed globulins, cucurbitin (pumpkin) and legumin (pea), are approximately spherical molecules of diameter ca. 8.8 nm composed of six subunits. In contrast, the hexameric 10 S storage protein from lupin seed, conglutin gamma, appears toroidal in shape with outer diameter ca. 10.3 nm and thickness ca. 2.2 nm. These results indicate that constraints imposed on seed proteins by their role in sustaining the germinating plant may have allowed a variety of different globulin structures to accumulate in the protein-storage bodies of seeds. PMID- 4037804 TI - Developmental regulation of the hepatocyte receptor for galactose-terminated glycoproteins. AB - The receptor which recognizes glycoproteins that have had their terminal sialic acids removed, thus exposing penultimate galactose residues (asialoglycoproteins), was examined for expression in rat liver during development. The level of asialoglycoprotein receptor binding activity in fetal rat livers was present in very low amounts but rose dramatically at the time of birth and reached adult levels by the second day after birth. Using immunoquantitation methods, it was found that the increased binding capacity of rat liver for asialoglycoproteins during development reflected accumulation of receptor molecules rather than activation of previously existing ones. The relative rates of synthesis of the predominant polypeptide of Mr 42,000 and the lesser abundant polypeptides of Mr 50,000 and 58,000 which comprise asialoglycoprotein receptor were found to increase in livers of fetuses near term and attain adult synthesis rates around birth. Thus, the accumulation of receptor protein molecules during development reflected increased synthesis of receptor polypeptides. These results suggest that the different gene products which code for the three forms of the receptor are coordinately expressed during development. Copurifying with asialoglycoprotein receptor during ligand affinity chromatography were polypeptides of Mr 25,000 and 27,000. These polypeptides display several characteristics similar to hepatic mannose binding lectin described by others. Onset of synthesis of the mannose binding lectin during development was analogous to asialoglycoprotein receptor but, in contrast, did not reach adult synthesis rates immediately after birth. PMID- 4037805 TI - Ganglioside sialidase distribution in mucolipidosis type IV cultured fibroblasts. AB - The subcellular distribution of ganglioside sialidase in Mucolipidosis IV (ML IV) cells was characterized by a series of Percoll gradients. Similar to normal cells, the enzyme cosedimented with plasma membrane markers, although this activity was reduced and exhibited decreased solubility in ML IV cells. Only trace amounts of ganglioside sialidase (less than 5%) was found in the lysosomes of normal cells. This activity was apparently reduced in ML IV cells but its minute activity in controls excluded further characterization of these differences. Plasma membranes on 6.7 and 5.6% Percoll gradients were biomodally distributed. Ganglioside sialidase in normal cells was found to be in both the heavier and the lighter membrane fractions, whereas the enzyme in ML IV cells was associated mainly with the denser membrane fraction. These data indicate that the enzyme in ML IV cells is characteristically different from normal in that it exhibits reduced activity and solubility and a different plasma membrane distribution. PMID- 4037806 TI - Calcium-dependent changes in properties of human prothrombin: a study using high performance size-exclusion chromatography and gel-permeation chromatography. AB - High-performance size-exclusion chromatography using a TSK 3000 SW column and aqueous gel filtration with Sephacryl S-200 SF have been used to characterize the effects of calcium ions on the hydrodynamic properties of human prothrombin and prethrombin 1. The results suggest that the effective hydrodynamic radius of prothrombin is less in the presence than in the absence of calcium ions. In addition, when using the TSK-3000 SW column, Ca2+-dependent formation of a hydrophobic site in the fragment 1 region of prothrombin results in an apparent further decrease in hydrodynamic radius. PMID- 4037807 TI - Amino acid sequence of high-redox-potential ferredoxin (HiPIP) isozymes from the extremely halophilic purple phototrophic bacterium, Ectothiorhodospira halophila. AB - The amino acid sequences of high-redox-potential ferredoxin (HiPIP) isozymes from Ectothiorhodospira halophila have been determined. These are: isozyme I, EPRAEDGHAHDYVNEAADPSHGRYQEGQLCENCAFWGEAVQDGWGRCTHPDFDEVLVKAEGWCSVYAPA S, and isozyme II, GLPDGVEDLPKAEDDHAHDYVNDAADTDHARFQEGQLCENCQFWVDYVNGWGYCQHPDFTDVLVRGEGW CSVYAPA. Isozyme II is the major form of HiPIP produced by the bacterium (65-80%) and is the most acidic of the known HiPIPs. The two isozymes are 72% identical to one another and require only a single residue deletion for alignment. Comparison of these HiPIPs with seven previously determined sequences revealed only 27% average identity. Both E. halophila HiPIP isozymes are likely to be functional since their sequences are equally distant from those of other species. The E. halophila HiPIP sequences show that H-bonding patterns recognized in Chromatium vinosum HiPIP are likely to be conserved and therefore cannot explain the unusually low redox potentials which have been reported. PMID- 4037808 TI - Involvement of the histidine residues in the pH-induced conformational change of histone H5. AB - Comparative studies on the conformational stability of histones H1 and H5 have been carried out by monitoring the pH-induced conformational transitions of the proteins by CD and 1H NMR spectroscopies. The transition point of H1 agrees with the pKa of the carboxyl groups of the acidic residues. In contrast, the transition of H5 is associated with the ionization of the histidine residues which exist exclusively in H5, as well as the deionization of the acidic residues. These observations, combined with the result of the deuterium exchange rates of the histidine C-2 protons, led us to conclude that His-25 and His-62, which are buried in the globular domain, play an important role in the conformational stability of histone H5. PMID- 4037809 TI - [A clinical trial of a new mitomycin C derivative, KW-2083 (7-N-(p-hydroxyphenyl) mitomycin C)]. AB - KW-2083 [7-n-(p-hydroxyphenyl)-mitomycin C] is a new mitomycin C (MMC) derivative. Its myelotoxicity was compared with that of MMC by using colony forming unit-spleen (CFU-S) from the femurs of C57BL/6 mice. As a result, it was estimated that the intensity of myelotoxicity of MMC was four times greater than that of KW-2083. Based on this data, a clinical trial of KW-2083 was conducted in 24 cases with various types of advanced solid tumors. KW-2083 was administered by i.v. injection at a dose of 40 mg/body every week. Out of 15 evaluable cases, a case of ovarian cancer showed a partial response. One case of each of ovarian cancer and gastric cancer showed minor response. However, as with mitomycin C, the dose-limiting toxicity of KW-2083 was leukopenia and thrombocytopenia. Other toxicities encountered were nausea, vomiting, anorexia, phlebitis and hepatic dysfunction. There were no cases with renal toxicity. Plasma concentration of KW 2083 was bioassayed in 3 cases who received 40 mg/body as an i.v. bolus injection. Plasma concentration-time curves fitted to a one-compartment model and half-life values averaged 27.6 min. The effective and low toxic dose schedules of KW-2083 should be investigated further. PMID- 4037810 TI - [Phase II study on MCNU in patients with advanced or recurrent gastrointestinal cancer]. AB - A phase II study on MCNU (Methyl 6-[3-(2-chloroethyl)-3-nitrosoureido]-6-deoxy alpha-D-glucopyranoside) was performed in 33 patients with advanced or recurrent gastrointestinal cancer under the cooperation of eight institutions in Hiroshima Prefecture. MCNU was given by means of intravenous drip infusion and the 33 cases were divided into three groups according to the method of administration; (A) 50mg/m2 every 1 or 2 weeks, (B) 70mg/m2 every 2 weeks or (C) 90mg/m2 every 6-8 weeks. Among 28 evaluable cases, 1 complete response (CR) and 1 partial response (PR) were observed and these two cases were gastric cancer patients. Platelet nadir occurred at the 3rd or fifth week after MCNU administration, but the leukocyte count was not so decreased. Subjective side effects were nausea, general fatigue and vomiting, but these were observed to be only mild. PMID- 4037811 TI - [Clinician-oriented and cytology-oriented autopsy. III. The pancreas]. AB - The autopsy is performed with multiple purposes such as medical education, searching direct cause of the death and researches. The first purpose of the autopsy is, however, a service for clinicians. The dissection technic should be determined to present the best clinical-pathological correlation of the lesions. In addition to the careful evaluation of the gross lesions of the pancreas, Smears (Imprints) of the lesions are most useful to make initial pathological diagnoses during autopsy examination. Multiple photographs illustrate both the gross pathological lesions and cytological data of the pancreas. PMID- 4037812 TI - Safety of over-the-counter hydroquinone bleaching creams. PMID- 4037813 TI - Ochronosislike pigmentation from hydroquinone bleaching creams. PMID- 4037814 TI - Painful palmar-plantar erythema in myeloproliferative disease. PMID- 4037815 TI - Cytarabine-induced palmar-plantar erythema. PMID- 4037816 TI - Thrombocytosis in a patient with secondary syphilis. PMID- 4037817 TI - Blistering distal dactylitis in an adult. PMID- 4037818 TI - The blind men and the elephant. Different views of small congenital nevi. PMID- 4037819 TI - A histologic comparison of congenital and acquired nevomelanocytic nevi. AB - A reliable microscopic differentiation of nevomelanocytic nevi (NMNs) as congenital or acquired would be useful in defining a histogenic relationship between cutaneous melanoma and congenital NMN. In order to delineate histologic differences between congenital NMN and acquired NMN, a standardized assessment was conducted blindly, using a sample of consecutive surgical specimens of NMN submitted to a children's hospital pathology file. Despite significant histologic differences between congenital NMN and acquired NMN, the lack of a reliable prevalence rate for the proportion of congenital NMNs among all NMN specimens submitted for pathologic examination precludes a precise estimate of predictive value for diagnosing a given NMN as congenital or acquired based on histologic features alone. The results of this study can be used neither to support nor to refute a histologic association between cutaneous melanoma and congenital NMN. PMID- 4037820 TI - Congenital nevi less than or equal to 10 cm as precursors to melanoma. 52 cases, a review, and a new conception. AB - Fifty-two congenital melanocytic nevi (CMN) as precursors to melanoma or severe melanocytic dysplasia were reviewed macroscopically and microscopically. Forty eight "small" CMN measured less than 10 cm in diameter. Histologically, only five reached to the lower third of the dermis or subcutis ("deep type"); the remaining 47 were limited to the upper two thirds of the corium ("superficial type"). There were 47 invasive melanomas, two in situ melanomas, and three severe focal melanocytic dysplasias. All melanomas were of "epidermal" origin and primarily of the superficial spreading type. The age at diagnosis ranged from 18 to 79 years. Prepubertal melanomas were not observed. Melanoma may also arise on small CMN. The most frequent origin of the melanomas in small CMN and the preferred age at manifestation seem to be different from that for giant nevi. PMID- 4037821 TI - Estrogen and progesterone receptors in melanocytic lesions. Occurrence in patients with dysplastic nevus syndrome. AB - Estrogen and progesterone binding studies in a series of 22 melanocytic lesions from 14 patients with the dysplastic nevus syndrome were done using a fluorescent estrogen and progesterone binding technique. Melanocytic lesions from these patients, including primary cutaneous melanomas, dysplastic nevi, and benign nevi, contained large numbers of estrogen and progesterone binding cells. Comparison is made to a series of control intradermal nevi that had little or no detectable estrogen or progesterone binding. Increased hormonal binding, and possibly responsiveness, is seen in melanomas, melanoma precursor lesions such as dysplastic nevi and congenital nevi, as well as benign nevi from patients with the dysplastic nevus syndrome. PMID- 4037822 TI - Papulovesicular light eruption. A defined subset of polymorphous light eruption. AB - A distinctive photodermatitis is seen commonly in tourists visiting Hawaii. Analysis of 150 cases revealed that the eruption is acute in onset following exposure to sunlight, is confined to exposed areas, and mainly affects young to middle-aged white women. The clinical presentation is remarkably uniform, consisting of papules, papulovesicles, or vesicles. These findings are consistent with a diagnosis of polymorphous light eruption (PMLE) and the histologic picture supports this diagnosis. Other clinical variants of PMLE were not seen in our patients, however, which suggests that this condition is more monomorphous than polymorphous. We suggest papulovesicular light eruption as a suitable name for this common and distinctive subset of PMLE. PMID- 4037824 TI - Neurosarcomatous malignant melanoma arising in a neuroid giant congenital melanocytic nevus. AB - We report a case of neuroid giant congenital melanocytic nevus (GCMN) in which a malignant schwannomalike tumor developed. Literature review reveals that neurosarcomatous differentiation occurs among malignant tumors arising in GCMNs, apparently with greater incidence in those GCMNs showing benign neuroid differentiation. Although the differences between neuroid melanocytes and Schwann's cells may be more conceptual than real, we believe that the current tumor arising within a melanocytic nevus is likely of neuroid melanocytic origin and best designated as neurosarcomatous malignant melanoma. PMID- 4037823 TI - Correlation of serum and urinary porphyrin levels in porphyria cutanea tarda. AB - A significant linear correlation was found between serum total porphyrin concentration and 24-hour total urinary porphyrin excretion in 18 patients with porphyria cutanea tarda sampled at diagnosis and during and after treatment on 73 occasions. This confirms that the serum porphyrin level parallels urinary porphyrin excretion and is an appropriate indicator of disease activity useful for monitoring patients in clinical practice. PMID- 4037825 TI - Lenticular psoralen photoproducts and cataracts of a PUVA-treated psoriatic patient. AB - Psoralen photoproducts were identified in association with cataracts in a psoriatic patient several years after oral methoxsalen plus ultraviolet A light (PUVA) therapy. Patients should be required to wear adequate optical protection not only during PUVA therapy but 24 hours following ingestion of methoxsalen. PMID- 4037826 TI - Late-onset erythropoietic protoporphyria with unusual cutaneous features. AB - A 68-year-old man with apparently light-exacerbated erythematous cutaneous plaques on his face and on the dorsa of his hands was found to have late-onset erythropoietic protoporphyria, diabetes mellitus, and hyperlipidemia. Extensive deposits of material that stained with periodic acid-Schiff were present in the lesional dermis. Monospecific antibody studies showed this material to be mainly type IV collagen. These findings strongly suggest that the lesions are a manifestation of erythropoietic protoporphyria. The late onset and asymptomatic unusual cutaneous lesions appear to be a new presentation of the disease. PMID- 4037827 TI - Bone lesions in xanthoma disseminatum. AB - A case of xanthoma disseminatum occurred in association with progressive bone lesions. This association has not been previously emphasized. PMID- 4037828 TI - Perforating pseudoxanthoma elasticum associated with chronic renal failure and hemodialysis. AB - A patient with hypertension and chronic renal failure of an undetermined cause who was undergoing hemodialysis developed bilateral crusted, focally eroded plaques on her breasts. A biopsy specimen of the lesional skin revealed typical histologic changes of pseudoxanthoma elasticum, with epidermal perforation. A biopsy specimen of lesion-free skin revealed characteristics typical of pseudoxanthoma elasticum. Perforating pseudoxanthoma elasticum should be added to the growing list of cutaneous disorders that occur in patients with chronic renal failure who are undergoing hemodialysis. PMID- 4037829 TI - Successful treatment of generalized discoid skin lesions with azathioprine. Its use in a patient with systemic lupus erythematosus. AB - A 20-year-old patient had systemic lupus erythematosus and extensive generalized discoid disease that failed to respond to conventional treatment with topical steroids and high doses of hydroxychloroquine sulfate (Plaquenil). The skin lesions responded dramatically to 100 mg of azathioprine sodium daily, flared when the drug treatment was discontinued, and again responded on reinstatement of the same dosage of azathioprine. The case report suggests that extensive discoid skin lesions can be successfully treated with oral azathioprine. PMID- 4037830 TI - Macroglossia. An unusual presentation of pemphigus vulgaris. AB - A 19-year-old woman presented with macroglossia of five months' duration and without bullae or erosions. A biopsy revealed a picture consistent with pemphigus vulgaris. The patient subsequently developed typical oral erosions. Her tongue enlargement and oral ulcerations improved dramatically with topical and systemic steroid therapy. Pemphigus vulgaris should be considered in the differential diagnosis of macroglossia. PMID- 4037831 TI - Actinomycetoma caused by Nocardiopsis dassonvillei. AB - We report a case of mycetoma caused by Nocardiopsis dassonvillei in a 39-year-old man. He had multiple nodules and draining sinuses on the anterior aspect of his right leg just below the knee. Few cream-colored granules were seen in the exudate. The biopsy specimen showed gram-positive, non-acid-fast granules with distinct borders. An aerobic actinomycete isolated from the lesion was identified as N dassonvillei. We think that this is the first reported case of mycetoma caused by N dassonvillei. PMID- 4037832 TI - Correlation of the vasoconstrictor assay and clinical activity in psoriasis. PMID- 4037834 TI - Hydroxyurea and pain in psoriatic lesions during ultraviolet-B radiation. PMID- 4037833 TI - Infectious eccrine hidradenitis in a patient undergoing hemodialysis. PMID- 4037835 TI - Mounting evidence of paraben sensitivity in dogs. PMID- 4037836 TI - Regression and other factors of prognostic interest in malignant melanoma. PMID- 4037838 TI - A histologic study of epithelial dysplasia in oral lichen planus. AB - One hundred cases of oral lichen planus were reviewed together with 100 nonspecific oral mucosal inflammatory lesions as a control group. The presence of dysplasia was noted, using well-established histologic criteria. Mild dysplasia was found in 57% of cases, moderate dysplasia in 9%, and severe dysplasia in 2% of cases. In the control group, mild dysplasia was observed in 32% of cases, moderate in 10%, and severe dysplasia was not present. It is suggested that, while mild or moderate dysplasia may not indicate precancerous potential, severe dysplasia in lichen planus may signify the development of a precancerous lesion. PMID- 4037837 TI - Regression in thin malignant melanoma. Microscopic diagnosis and prognostic importance. AB - Forty-eight malignant melanomas of the extremities, 1 mm or less in maximal thickness, were studied to better define microscopic criteria of regression in thin melanomas. Eleven tumors (23%) exhibited definite regression in the form of one or more segmental areas (defects) where the invasive component was replaced by mononuclear cell infiltrate and fibrosis. Thirteen other tumors (27%) had diffuse, nonsegmental changes classified as probable regression. Nineteen lesions (40%) lacked regression, although 14 of these contained focal evidence of host response. Five melanomas (17% of lesions less than 0.75 mm thick) were equivocal for regression. There were no recurrences or metastases. The histologic diagnosis of regression in thin melanomas requires subjective judgments, but segmental defects represent a potentially reproducible criterion. Their width can be measured, and the proportion of the melanoma that has undergone regression can be estimated. The preponderance of data from the literature, supported by this study, indicates that regression has no prognostic importance in the vast majority of thin melanomas. There are observations, however, to suggest that in rare cases, regression may negate the prognostic value of microstaging of a thin melanoma. To date, the type and extent of such regressive changes have not been adequately defined. PMID- 4037839 TI - Leukocytoclastic vasculitis in urticaria induced by ultraviolet irradiation. AB - A 35-year-old woman would develop urticarial lesions over one to four hours after irradiation with sunlight or artificial ultraviolet radiation. Lesions could persist for days before resolving. Although lesions were morphologically typical of solar urticaria, their evolution and resolution were both much slower than expected. Histologically, the lesions showed leukocytoclastic vasculitis. This unexpected finding suggests the possibility that there may be novel mechanisms involved in the pathogenesis of some cases of solar urticaria. PMID- 4037840 TI - Congenital migratory ichthyosiform dermatosis with neurologic and ophthalmologic abnormalities. AB - We encountered two patients with a congenital migratory ichthyosiform dermatosis, retinal colobomas, conductive hearing loss, seizures, mental retardation, and similar facial features. The results of electron microscopic studies performed on skin biopsy specimens from the patients differed significantly from those of previously reported cases of ichthyosiform dermatoses with associated neurologic and ophthalmologic abnormalities; they appear to represent a new neuroectodermal syndrome. PMID- 4037841 TI - What is the function of melanin? PMID- 4037842 TI - Chloroquine-induced hypopigmentation of hair and freckles. Association with congenital renal failure. AB - Hypopigmentation of hair and freckles occurred in a patient receiving chloroquine sulfate therapy. This patient had a severe congenital renal failure that presumably increased plasma and tissue levels of the drug substantially, accounting for the hypopigmentation. PMID- 4037843 TI - Ichthyosis follicularis with alopecia and photophobia. AB - We treated two unrelated boys with ichthyosis follicularis, a rare skin disorder characterized by extensive noninflammatory spiny follicular hyperkeratoses, severe photophobia, and generalized noncicatricial alopecia. This disorder must be differentiated from keratosis follicularis spinulosa decalvans; ulerythema ophryogenes; keratosis pilaris rubra atrophicans faciei; atrichia with papular lesions; atrophodermia vermiculata; and keratitis, ichthyosis, and deafness syndrome, all of which share some clinical features. Ichthyosis follicularis with alopecia and photophobia appears to be a familial disorder, but too few cases have been reported to establish the exact mode of inheritance. PMID- 4037844 TI - Lymphomatoid papulosis associated with plaque-stage and granulomatous mycosis fungoides. AB - A 47-year-old black man had typical papulonodular lesions of lymphomatoid papulosis (LyP) with concurrent plaque-stage mycosis fungoides (MF). Both diagnoses were confirmed histologically. This supports the concept that LyP is part of the spectrum of cutaneous T-cell lymphoproliferative disorders. The patient also had a large nodule and a deeply infiltrated plaque, each of which exhibited a deep granulomatous reaction. These were interpreted as representing granulomatous MF. Clinically, there was an evolution from a predominance of LyP lesions to a predominance of MF plaques. Topical carmustine therapy resulted in a substantial decrease in the number and size of both LyP and MF lesions. Both lesion types involuted with hypopigmentation. PMID- 4037845 TI - Mycosis fungoides-like lesions associated with phenytoin therapy. AB - An 83-year-old woman developed generalized lymph node hyperplasia together with mycosis fungoides-like skin lesions 11 months after institution of anticonvulsant therapy with phenytoin. The clinicopathological changes disappeared completely three weeks after cessation of therapy. This circumstantial evidence together with the known data on the association of phenytoin with lymphoproliferative disorders suggest that it was the phenytoin that was responsible for the patient's condition. This case had features similar to those associated with the pseudo-mycosis fungoides syndrome except that the cutaneous lesions consisted of two localized erythematous plaques, with no generalized exfoliative erythrodermic dermatitis. Nonetheless, we believe that the use of the term pseudo-mycosis fungoides for this and similar cases would be appropriate. PMID- 4037846 TI - Junctional epidermolysis bullosa and pyloric atresia in two siblings. AB - Pyloric atresia is a rare disorder that has been seen in association with epidermolysis bullosa. Two male siblings with pyloric atresia and the junctional form of epidermolysis bullosa, confirmed by electron microscopy, are described herein. These cases strengthen the relationship between junctional epidermolysis bullosa and pyloric atresia, which are probably transmitted together in an autosomal-recessive pattern. PMID- 4037847 TI - Lichen nitidus with plasma cell infiltrate. AB - The predominant cell types in the dermal infiltrate of lichen nitidus are lymphocytes and epithelioid cells. We report two cases of lichen nitidus in which numerous plasma cells were present in the dermal infiltrate. PMID- 4037848 TI - Dermatobia hominis dermal myiasis. A furuncular lesion in a world traveler. AB - A case of botfly myiasis occurred in a patient who traveled to Brazil. This infestation resembles a pyogenic furuncle, but should be a diagnostic consideration when it does not respond to antibiotic therapy in a world traveler. PMID- 4037849 TI - Hypertrichotic skin-colored patches in an infant. Congenital smooth-muscle hamartoma (CSMH). PMID- 4037850 TI - 'The State of the World's Children'. PMID- 4037851 TI - Second primary tumours. PMID- 4037852 TI - Cranial ultrasound in preterm infants: long term follow up. AB - One hundred and twenty nine high risk preterm infants (gestational ages 26-36 weeks, mean 31.2 weeks; birth weights 800-3880 g, mean 1490 g) were studied by cranial ultrasound during the neonatal period, over a period of one week to three months, and at the age of 1 year. Neonatal ultrasound scanning was performed with an ATL Mk III real time echoscope, and follow up ultrasound scans at the age of 1 were performed with an Octoson static compound scanner. The neonatal scans of 66 infants were abnormal. Cerebroventricular haemorrhages were detected in 53 infants and other lesions in 19, six of whom also had haemorrhages. Posthaemorrhagic changes developed in 30 infants. The follow up scans at 1 year were abnormal in 27 children. One large parenchymal cyst was detected. All 27 scans showed ventricular dilatations; 19 were asymmetrical. About 95% of the children with normal neonatal scans and 60% with abnormal neonatal scans had normal scans at 1 year. The size and shape of the ventricular system had changed in 20% of all infants. As no major changes were seen in the ultrasound images of those studied beyond the age of 2 months cranial ultrasound follow up in high risk preterm infants should therefore be continued until the age of 2-3 months; follow up beyond that age would only rarely be necessary. PMID- 4037853 TI - Posthaemorrhagic hydrocephalus in newborn term infants. AB - Intraventricular haemorrhage may occur de novo in previously well, term newborn infants. In a group of six neonates a high incidence of posthaemorrhagic hydrocephalus was found. Posthaemorrhagic hydrocephalus may be more common in full term newborn infants than previously recognised. PMID- 4037854 TI - Improvement in auditory and visual evoked potentials in jaundiced preterm infants after exchange transfusion. AB - Two preterm infants with peak serum bilirubin concentrations of 270 mumol/l and 200 mumol/l, respectively showed improvement in the wave peak latencies of the auditory and visual evoked potentials after exchange transfusion. The implications of this observation and the use of evoked potential recording in neonatal jaundice are discussed. PMID- 4037855 TI - Insufficient early weight gain in preterm babies and influence on weight at 12 months. AB - Relations between the amount and duration of insufficient early gain in weight and later catch up and absolute weight at 1 year of corrected age were investigated in 30 preterm babies of greater than 32 weeks' gestation. There were no significant correlations to suggest that insufficient early weight gain affected later patterns of weight despite individual weights at 1 year generally being distributed in lower centile channels. These findings have important clinical implications for the feeding of preterm babies. PMID- 4037857 TI - Short term histological liver changes in extrahepatic biliary atresia with good postoperative bile drainage. AB - Short term histological liver changes were studied in 13 patients with congenital biliary atresia, who showed good bile drainage after radical operation. Biopsies obtained at the time of the corrective surgery and at the second operation to convert from external total to partial bile drainage (undertaken once the bilirubin concentration was less than 30.8 mumol/l) were compared. A significant correlation was found between histological findings and the clinical course. In particular, at the second biopsy an increase in hepatic fibrosis and cell infiltration was observed mainly in patients whose bilirubin concentration decreased slowly or who had cholangitis, or both. Hepatic fibrosis and cell infiltration had decreased, however, in an appreciable number of patients whose postoperative course had been characterised by a rapid reduction in the bilirubin concentration and no cholangitis. PMID- 4037856 TI - Development of IgE and IgG antibodies to food and inhalant allergens in children at risk of allergic disease. AB - In a prospective study of 92 children with at least one atopic parent, the development of the specific antibody responses to food and inhalant allergens during the first 5 years of life were assessed. By the radioallergosorbent test egg specific IgE antibody occurred in about 30% of the children with the mean peak concentration at 12 months. By the second year the prevalence of this antibody had increased whereas the mean concentration had decreased. Milk specific IgE antibody could not be shown in any subject, including four whose skin tests yielded positive results. Food specific IgG antibody was noted by antigen binding radioimmunoassays at 3 months in most children. These responses had peaked and began to fall by the fifth year. In contrast few children had detectable IgE or IgG antibody to inhalant allergens before the first 2 years of life. Both the concentration and prevalence of specific antibody, however, increased from the second to the fifth year and was greater in children whose skin tests yielded positive results. Breast feeding was associated with an increase in the prevalence of positive results from skin tests but was not associated with detectable IgE antibody to both food proteins, a lower concentration of IgG antibody to cows' milk, and was not associated with protection against the development of disease. A high level of exposure to dust mite was associated with an increased prevalence of positive results from skin tests to dust mite and appreciably higher antibody concentration. This study indicates differences in the humoral responses to food and inhalant allergens. Environmental factors appear to influence the development of these responses. PMID- 4037858 TI - Results and complications of surgery for gastro-oesophageal reflux. AB - One hundred and six children undergoing antireflux surgery were studied; 41 were severely mentally retarded and 29 had reflux strictures. Although the eventual rate of success was 92%, 20 patients developed complications that required a second operation. Prolapse of the fundoplication into the mediastinum was the commonest complication (in seven patients), followed by intestinal obstruction (in five), and intractable fibrous oesophageal strictures (in five). The incidence of postoperative complications was highest in patients with mental retardation or oesophageal strictures. Referral of these patients for operation was invariably delayed, and earlier referral may have avoided many of the complications. PMID- 4037859 TI - 17/7 translocation trisomy: practical vindication of a model of sickness. AB - A girl was seen by a psychiatrist for relentless rubbing of her eyes and difficult behaviour. A proper diagnosis of her sickness required an understanding of the cause of her physical stigmata, which disclosed a previously undescribed chromosome anomaly (partial trisomy 17p); her mental handicap and behavioural disorder, which were partly a function of parental despair; and the predicament of her father and other carrier relatives who were identified through this child. Explanation or alteration of each component of sickness was necessary to achieve beneficial change. PMID- 4037860 TI - Interstitial nephritis of acute onset. AB - Interstitial nephritis was diagnosed at renal biopsy in 10 previously healthy children. All had identical clinical symptoms: anaemia, raised sedimentation rate, low glomerular filtration rate, protein and leucocytes in the urine, but no bacteria; nine also had glycosuria. Six of the children had a history of recent ingestion of drugs or a serologically proved infection, or both. One child later developed uveitis. After the acute phase all made at least partial recovery, but after a mean follow up of two years and eight months only four were without any signs of disease, three had equivocal findings, two definite renal disease, and one renal failure. Interstitial nephritis, therefore, seems to be a clinical entity often occurring without known cause or triggering factor, its prognosis is variable, and some patients may develop chronic renal failure. PMID- 4037861 TI - Concentrations of lead in maternal blood, cord blood, and breast milk. AB - Lead concentrations in maternal blood, umbilical cord blood, and breast milk from 114 women who were not occupationally exposed to lead were determined by graphite atomic absorption spectrophotometry. The mean concentrations of lead in maternal blood, umbilical cord blood and breast milk were 0.7, 0.55, and 0.23 mumol/l, respectively. A significant correlation was observed between maternal and umbilical cord blood (r = 0.63). A lower correlation was noted between maternal blood and breast milk (r = 0.29). These results suggest that lead freely crosses the placental barrier from mother to fetus and the transfer of this heavy metal from maternal tissues to breast milk is possible, but the metabolic mechanisms are more complicated. In addition, a longitudinal study was conducted of concentrations of lead in breast milk in nine lactating women. Results suggested no significant change in the content of lead in breast milk during early lactation. PMID- 4037863 TI - Hypertrichosis due to primary hypothyroidism. AB - A 10 year old girl with hypertrichosis associated with primary hypothyroidism that resolved after 6 months' replacement treatment with thyroxine is reported. It is important to consider the diagnosis of hypothyroidism in children with abnormal hairiness or distribution of body hair. PMID- 4037862 TI - Alcohol intoxication, an underdiagnosed problem? AB - To show that alcohol intoxication may be underdiagnosed in childhood, we describe four patients in whom it was not suspected until blood alcohol concentrations were measured as part of a toxicology screen. PMID- 4037865 TI - Treatment of asthma in preschool children with slow release theophylline. AB - Fifty two preschool children with asthma were given a recommended regimen of slow release theophylline. There was wide variation in the metabolism of theophylline. The approach adopted gave disappointing results. Nine children did not comply, and 16 stopped treatment because of side effects. Of the remainder, control of asthma was poor in 15 and satisfactory in 12. PMID- 4037864 TI - Pubertal growth in diabetics. AB - Mean values for two variables of the pubertal growth spurt, peak height velocity and age at peak velocity, of children attending the diabetic clinic in Bristol are reported. The growth spurt was normal both in timing and intensity in boys, but the peak velocity was reduced and age at peak velocity more variable among girls. PMID- 4037866 TI - Lactation nurse increases duration of breast feeding. AB - In a randomised controlled trial a lactation nurse assisted mothers during the early weeks after parturition both in hospital and at home. All mothers who started breast feeding were entered into the trial. The lactation nurse significantly extended duration in the study group compared with controls, particularly during the first four weeks and among women of lower social class. PMID- 4037867 TI - Training of paediatricians for psychosocial aspects of their work. PMID- 4037868 TI - . . . and children first? PMID- 4037869 TI - Oxandrolone in low dose for constitutional delay of growth and puberty in boys. PMID- 4037870 TI - A microbial assay for determining the influence of physicochemical environmental factors on the toxicity of organics: phenol. PMID- 4037871 TI - Forestry workers involved in aerial application of 2,4-dichlorophenoxyacetic acid (2,4-D): exposure and urinary excretion. PMID- 4037872 TI - Effects of vitamins E and A on 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-induced lipid peroxidation and other biochemical changes in the rat. PMID- 4037873 TI - Survival, growth, and histopathological effects of paraquat ingestion in nestling American kestrels (Falco sparverius). PMID- 4037874 TI - Biochemical responsiveness of a bovine kidney cell line to inorganic mercury. PMID- 4037875 TI - [Persistent generalized adenopathies in subjects at high risk of AIDS. Diagnostic and prognostic value of lymph node lesion syndromes. Apropos of 8 cases]. PMID- 4037876 TI - [Disseminated peritoneal leiomyomatosis. Apropos of 2 new cases]. PMID- 4037877 TI - [Amyloid goiter. Apropos of a case]. PMID- 4037878 TI - [Ultrastructural study of the lacrimal gland in Gougerot-Sjogren syndrome]. PMID- 4037879 TI - [Incidence of mycoses and parasitic diseases in female genital infections. Existence of a correlation with hormonal status. Demonstration of seasonal changes]. PMID- 4037880 TI - [Pathologic profile of cancers of the nasopharynx in Algiers. Apropos of 210 cases seen over 2 years]. PMID- 4037881 TI - [Intramyocardial megamitochondria in fibroelastosis of the endocardium: known and enigmatic fact]. PMID- 4037882 TI - [Pregnancy toxemia and hyperplasia of the juxtaglomerular apparatus]. PMID- 4037883 TI - [Cancer in Morocco (1950-1980). According to the records of various laboratories of pathologic anatomy]. PMID- 4037884 TI - [Acute adrenal insufficiency caused by cholesterol emboli]. PMID- 4037885 TI - Articular manifestations of familial hypercholesterolaemia. AB - Familial hypercholesterolaemia is characterised by a decreased removal of low density lipoproteins and premature coronary artery disease. Tendinous xanthomata are a hallmark of the disease. The affected joints may also be the sites of inflammation and pain. Arthropathy has been associated mainly with the homozygous form of familial hypercholesterolaemia, but it is also known to occur in the heterozygous form. We report on the articular manifestations in 73 patients with heterozygous familial hypercholesterolaemia. About 40% of these patients had at least one episode of articular symptoms. The observed articular manifestations may be classified into four types: Achilles pain (18%), Achilles tendinitis (11%), oligoarticular arthritis (7%), polyarticular or rheumatic fever-like arthritis (4%). It is concluded that in heterozygous familial hypercholesterolaemia articular manifestations are frequent, diverse, and may be the first symptom of this metabolic disorder. PMID- 4037887 TI - Oesophageal dysfunction in patients with primary Sjogren's syndrome. AB - Oesophageal motility was studied in 22 patients with primary Sjogren's syndrome and 20 normal volunteers. Oesophageal dysfunction was detected in eight of the 22 patients (36.4%) with primary Sjogren's syndrome. No abnormalities were detected in the normal subjects. Individual analysis of the oesophageal motility studies showed different patterns of oesophageal dysfunction; aperistalsis (three patients), triphasic tertiary contractions (two patients), frequent non peristaltic contractions (two patients), and low contractions (one patient). These oesophageal abnormalities did not correlate with the parotid flow rate, the degree of inflammatory infiltrate of the minor salivary glands, the extraglandular manifestations, or the presence of autoantibodies. PMID- 4037886 TI - Decreased nailfold capillary density in Raynaud's phenomenon: a reflection of immunologically mediated local and systemic vascular disease? AB - Nailfold capillary patterns were studied in 107 patients with Raynaud's phenomenon (RP), including patients wih (n = 39) and without (n = 68) connective tissue disease (CTD). Capillary density was decreased in patients with sclerodactyly, digital ulcers, tuft resorption, and telangiectasia, compared with patients without these symptoms. In addition, an inverse relationship was found between the severity of RP at first presentation (as graded by photoelectric plethysmography during cooling) and the capillary density in patients with CTD (r = -0.45; p less than 0.05). In the total group of patients nailfold capillary density was inversely related to organ system involvement (r = -0.52; p less than 0.01). Decreased nailfold capillary density was observed, in particular, in patients with oesophageal hypomotility and in patients with chest x-rays compatible with interstitial fibrosis. As to factors supposedly involved in the pathogenesis of vascular changes in CTD, the presence of autoantibodies, increased levels of circulating immune complexes, and increased levels of acute phase reactants were all associated with a decreased number of nailfold capillaries. We conclude that loss of nailfold capillaries as observed by microscopy is a reflection of local and systemic vascular disease. PMID- 4037888 TI - Ultrastructural changes in the rectal mucosa of patients with rheumatoid arthritis. AB - The rectal mucosa from patients with severe rheumatoid arthritis has been examined by electron microscopy. Initially the patients were biopsied for investigation into the diagnosis of amyloidosis or vasculitis, which proved to be negative. A range of ultrastructural abnormalities was found which included proliferation of the rough endoplasmic reticulum, mitochondrial inclusions, association of the mitochondria with cytoplasmic filaments, and marked increase in the number of iron containing siderosomes. Most of these abnormalities have already been reported in rheumatoid synovial tissue, and attention is drawn to the similarity in findings between these two sites. PMID- 4037889 TI - Mitral and aortic regurgitation in Behcet's syndrome. AB - A 35-year-old man with definite Behcet's disease developed acute mitral and aortic regurgitation. Valvular disease, we believed, was another manifestation of this disease. Cardiac involvement in Behcet's disease and the role of prednisone therapy are discussed. PMID- 4037891 TI - [A tropical medicine society. Why?]. PMID- 4037890 TI - Seatone in rheumatoid arthritis. PMID- 4037892 TI - [Medicinal plants in developing countries]. PMID- 4037893 TI - Malaria control by village health workers in the province of Dosso, Niger. Part. 1. Operational analysis. PMID- 4037894 TI - Malaria control by village health workers in the province of Dosso, Niger. Part. 2. Epidemiological impact. PMID- 4037895 TI - [Assessment of a focus of schistosomiasis caused by Schistosoma mansoni in Mayombe, Republic of Zaire]. PMID- 4037896 TI - [Distribution of Necator americanus and Ancylostoma duodenale in Santa Cruz, Bolivia]. PMID- 4037897 TI - [Clinical aspects of early congenital syphilis]. PMID- 4037898 TI - Methods to calculate survival rate in tsetse fly (Glossina) populations. PMID- 4037899 TI - Colostral transfer of antibodies to Trypanosoma brucei in goats. PMID- 4037900 TI - Lassa virus lethality for inbred mice. PMID- 4037901 TI - [A case of hypereosinophilia originating in Africa]. PMID- 4037902 TI - Implantable infusion pump management of insulin resistant diabetes mellitus. AB - Diabetes mellitus with resistance to insulin administered subcutaneously or intramuscularly (DRIASM) is a rare and brittle form of Type I diabetes, found predominantly in young females and characterized by inadequate glycemic response to subcutaneous or intramuscular insulin administration. DRIASM leads to frequent ketoacidosis and obligatory hospitalization for administration of intravenous insulin. The use of a totally implantable infusion pump effected dramatic improvement in the treatment of five patients with this difficult form of diabetes. Frequency of clinical ketoacidosis was reduced from 37 episodes per year to 0.4 episodes per year (99%), and average in-hospital days per month were reduced from 20.8 days to 2.2 days (89%) with a mean follow-up period of 14.4 months. Cost savings were approximately +10,000 per patient month. Quality of life was greatly improved for these individuals. PMID- 4037903 TI - Blunt multiple trauma (ISS 36), femur traction, and the pulmonary failure-septic state. AB - Fifty-six blunt multiple trauma patients (HTI-ISS 22-57) were studied for the effects of immediate versus delayed internal fixation of a femur or acetabular fracture on the pulmonary failure septic state. The pulmonary failure septic state may be defined as an alveolar arterial oxygen tension difference greater than 100, plus fever and leukocytosis. These patients were divided into four groups. Group I (N = 20) had immediate internal fixation, postoperative ventilatory support, and was sitting up at 30 hours. Group II (N = 20) had 10 days of femur traction and postoperative ventilatory support. Group III (N = 9) was immediately extubated after surgery and had 30 days of femur traction. Group IV (N = 7) had special circumstances that should increase the duration of the pulmonary failure septic state. These four groups of patients were statistically identical by 20 different criteria on admission except that Group I had more recognized chest injuries than Group II (12 vs. 9). Group I required 3.4 +/- 2.6 days of ventilator support and 7.5 +/- 3.8 intensive care unit (ICU) days; they had 12 +/- 8.8 elevated white counts, 3.8 +/- 4 febrile days, 0.05 positive blood cultures per patient, four fracture complications out of 93 fractures, 59 injections of narcotics, and 23 +/- 8.6 acute care days. Ten days of femur traction doubled the duration of the pulmonary failure septic state relative to Group I at a statistically significant level for nine out of 10 criteria, while increasing the number of positive blood cultures by a factor of 10, the number of fracture complications by a factor of 3.5, and the use of injectable narcotics by a factor of 2. Thirty days of femur traction increased the duration of the pulmonary failure septic state relative to Group I by a factor of 3 to 5 for all criteria at a statistically significant level, while increasing fracture complications by a factor of 17, positive blood cultures by a factor of 74, and the use of narcotics by a factor of 2. Group IV, which had four out of seven immediate internal fixations, behaved similarly to Group II. Femoral shaft traction should be avoided in the blunt multiple trauma patients because it greatly increases the cost of care and the risk of multiple systems organ failure.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 4037904 TI - CEA-directed second-look surgery in the asymptomatic patient after primary resection of colorectal carcinoma. AB - Since 1971, serial carcinoembryonic antigen (CEA) levels have been measured to monitor patients after primary resection of colorectal cancer. Based solely on a rise in CEA level above the baseline established after primary resection, 146 patients were readmitted to the hospital. Chest films, liver-spleen scan, colonoscopy, bone scan, abdominal and pelvic CAT scan, and hepatic arteriograms were performed, and elevated CEA levels were confirmed before reexploration was undertaken. In the 146 patients, 139 (95%) had recurrences, and 81 (58%) of these were resectable for potential cure. Two of the first 22 patients re-explored between 1971 and 1975 are still living 11 and 14 years after second look; of 45 patients reoperated upon from 1976 through 1979 and followed for at least 5 years, 14 (31%) are still living. A rise in CEA above the baseline established after primary resection proved to be a sensitive indicator of recurrence and prompted reexploration before symptoms developed. Early alternative therapy was begun in patients with unresectable recurrences. PMID- 4037905 TI - The influence of splenic weight and function on survival after experimental pneumococcal infection. AB - Splenectomy impairs survival after pneumococcal challenge in rats, while preservation of sufficient splenic tissue can be protective. This study investigated the effects of methylcellulose on stimulation of splenic weight, splenic histology, reticuloendothelial (RE) activity, and survival after pneumococcal infection. Methylcellulose increased spleen weight four- to five fold but did not improve RE function or survival after infection. These parameters correlated best with the weight of the remnant in animals that did not receive methylcellulose. The functional limitations of splenic autotransplants were not corrected by methylcellulose stimulation of splenic weight. Preservation of a splenic remnant with intact blood supply is preferable to autotransplantation of the spleen to conserve RE capability. PMID- 4037906 TI - Role of the vascular endothelial cell antigen system in the etiology of atherosclerosis. AB - An autoantibody directed against an antigen system that is expressed on the vascular endothelial cell (VEC) was recently identified in random patients with peripheral vascular disease. This VEC antigen system is also present on the peripheral blood monocyte but not on any other cell type studied to date. In a randomized study of 112 patients with peripheral vascular disease at the Albany Medical College, 46% demonstrated an autoantibody against their autologous monocytes and VEC. This autoantibody is a highly cytotoxic, complement-fixing antibody directed against VEC antigens. It does not crossreact with autologous T or B lymphocytes and appears to be highly polymorphic. It is present in only nine per cent of the age-matched controls and was never detected in young controls. This preliminary investigation suggests that immunological injury may be the initiating factor in the development of atherosclerotic lesions more frequently than currently appreciated. Whether this autoantibody to VEC is the result of or the cause of endothelial cell damage in these patients is still under study. PMID- 4037907 TI - A ten-year experience with ninety-two cases of Hirschsprung's disease. Including sixty-seven consecutive endorectal pull-through procedures. AB - From July 1974 through November 1984, 92 patients with Hirschsprung's disease (congenital aganglionosis) have been treated at the University of Michigan-Mott Children's Hospital. This series includes 67 consecutive modified endorectal pull through (ERPT) procedures in children. Fifty-one of these 67 patients had standard rectosigmoid disease and underwent a successful ERPT with only two major complications. One of these 51 children underwent a successful ERPT but died in the late postoperative period from severe congenital heart disease. Eighteen of the 92 patients suffered from total aganglionosis or long-segment disease. Sixteen of these have undergone an ERPT with no mortality or operative morbidity. The follow-up ranges from 6 months to 10 years. All of the children who have reached 3 years of age are continent. Of the remaining 23 patients, 12 were referred following an unsuccessful pull-through at another hospital. The 12 operations included five Swenson pull-throughs, five Duhamel procedures, one ERPT, and one subtotal colectomy. It was possible to redo or revise the pull through procedures successfully in all but one patient, who required a permanent colostomy. Finally, 11 children were referred for management of a variety of complications following pull-through procedures performed at other institutions. None of these 11 patients required a reperformance of their pull-through, and all were successfully treated with lesser surgical procedures or with medical management. The excellent functional results and the low morbidity and zero operative mortality are attributed to the technical ease of performing the modified ERPT. PMID- 4037908 TI - Prophylactic postoperative nasogastric decompression. A prospective study of its requirement and the influence of cimetidine in 200 patients. AB - To determine the need for prophylactic nasogastric decompression following laparotomy and the influence of cimetidine, 200 consecutive patients who underwent major abdominal procedures were prospectively randomized into one of four limbs: no tube-placebo; no tube-cimetidine; tube-placebo; and tube cimetidine. Patients were evenly distributed among these groups with respect to age, sex, alcohol and tobacco use, previous operations, and types of operations. There was significantly longer time until passage of flatus, bowel movement, and cessation of intravenous fluids in the tube group (p less than 0.05). Duration of postoperative stay increased from 11.4 to 14.1 days in the intubated patients (p less than 0.05). There was also significantly more pain with and frequency of swallowing, and nose/throat discomfort in the tube group. Nasogastric tubes reduced the incidence of vomiting from 28 in the no-tube group to 10 in the tube group (p less than 0.05), but most had only one or two episodes. Cimetidine did not affect either the incidence of vomiting or the duration of intubation, but was associated with a significant increase in pneumonias (p less than 0.05). Five patients without tubes initially, and seven patients with tubes had to have them inserted or replaced for vomiting or abdominal distention, which occurred equally in the placebo and cimetidine limbs. There were no cases of aspiration pneumonia, gastric dilatation, or wound dehiscence in the trial, and the four anastomotic leaks were divided equally between the tube and no-tube groups. The results indicated that prophylactic decompression was unnecessary in most patients and associated with increased morbidity and delayed return of gastrointestinal function. Cimetidine lowered nasogastric output on the first postoperative day (p less than 0.05), but did not prevent vomiting. PMID- 4037909 TI - Retrieval of renal function by revascularization. Study of preoperative outcome predictors. AB - Results of renal revascularization for retrieval of function in poorly functioning kidneys are variable, but criteria for prediction of benefit and patient selection for operation are ill-defined. This report examines preoperative parameters in 64 hypertensive patients who underwent successful revascularization of poorly functioning kidneys as defined by creatinine clearance less than or equal to 15 ml/min (measured by preoperative split renal function studies [SRFS]) or preoperative serum creatinine greater than or equal to 3.5 mg/dl (range: up to 8.9 mg/dl) to identify markers of value in prediction of a beneficial response in renal function. Ages ranged from 35 to 75 years. There were 35 men and 29 women. The renovascular lesion was atherosclerotic in 58 patients and fibrodysplastic in six. Total renal artery occlusion was present in 32 cases. No urine flow was detectable before surgery on SRFS from 13 kidneys. Kidney lengths ranged from 7.7 cm to 15.1 cm. Fifty-four unilateral and 10 bilateral revascularizations were performed. A beneficial blood pressure response to operation was observed in 94%. Benefit in excretory function was determined by comparison of preoperative and postoperative data which included SRFS parameters, renal length, serum creatinine, isotopically derived split functioning renal mass, and glomerular filtration rates. Overall, 56 patients could be classified in regard to functional response. Twenty-two patients received no or minimal benefit; nine patients received modest improvement, and 25 patients exhibited more marked improvement. Statistical evaluation of preoperative anatomic and functional parameters as predictors of functional response suggested that multiple variables influence the probability of function retrieval by revascularization. Useful among these predictive variables are the status of the distal vessel beyond the occlusion, the bilaterality of reconstructable disease in azotemic patients, the amount of residual renal mass available for revascularization, and the degree of hyperconcentration of nonreabsorbable solutes from the involved kidney after surgery. PMID- 4037911 TI - Treatment of thoracic battle injuries versus civilian injuries. PMID- 4037910 TI - Mitral replacement: clinical experience with a ball-valve prosthesis. Twenty-five years later. AB - The purpose of this report is to review the results of mitral valve replacement since a first report in the Annals of Surgery in 1961, in order to determine the relative importance of new valve designs versus other surgical variables. The continued use of the silastic ball valve in its 1966 configuration (Model 6120), by providing a comparative data base for other new prosthetic valves, allows this analysis. For a valid comparison with the tilting disc (Bjork-Shiley) and the porcine (Hancock and Carpentier-Edwards) valves, only results with the silastic ball valves implanted during comparable time frames should be used. (Formula: see text) Thus, there are no significant differences in the results obtained with the silastic ball valve in time frames comparable to other contemporary valves introduced in the early 1970s. Improved results, therefore, must be non prosthetic valve related. PMID- 4037912 TI - Thoracic battle injuries in the Lebanon War: review of the early operative approach in 1,992 patients. AB - The effectiveness of aggressive resuscitation and early surgical intervention is evaluated in 1,992 casualties with thoracic battle wounds in Lebanon. The mechanism of injury was mainly high-velocity missiles and shelling in city battles. Ninety-seven percent of the wounds were penetrating. The mean age of the wounded was 20 years and the average transport, 4.2 km (3 miles). Logistics and newly equipped thoracic centers aided uniform therapy. For decompensating patients or those in critical condition, initial shock was treated with rapid volume expansion, cardiopulmonary support, and urgent thoracotomy. Thoracotomy was required in 1,422 casualties (71%) and definitive tube thoracostomy in 29%. Three hundred ten patients had pulmonary resections: 36 pneumonectomies, 112 lobectomies, and 162 segmental resections. In 627 patients following primary thoracotomy survival was 98.4%. For 456 casualties with additional systemic procedures, survival was 96.9%. For 285 casualties with cardiac injuries, a significant 14% incidence, overall survival was 73%. Survival was best for those with pericardial and coronary vessel wounds and dropped to 46% for those with left ventricular injuries. Survival was 87% among 54 patients with great vessel wounds. Life salvage in 726 (36%) patients was documented to result from early open procedures. Other benefits of this approach are presented in this broad based study. PMID- 4037913 TI - A survey of 77 major infectious complications of median sternotomy: a review of 7,949 consecutive operative procedures. AB - Sternal wound infections developed following 77 (0.97%) of 7,949 operative procedures involving median sternotomy at New York University Medical Center from 1976 to 1984. Risk factors associated with the development of a sternal wound infection included combined revascularization and valve replacement, early reexploration for bleeding, prolonged low cardiac output syndrome, and prolonged ventilatory support (greater than 24 hours). Concomitant infection at other sites with the same organism as cultured from the sternum was present in 42% of the patients. Thirty-seven patients (48%) were treated with radical debridement followed by closed antibiotic irrigation. In 31 other patients (40%), the wounds were debrided and left to heal by open granulation. Both initial treatments had equally high success rates (78.4% and 74.2%, respectively). However, the open granulation method resulted in a hospital stay that was an average of 10 days longer than the closed antibiotic irrigation method. Muscle flaps were used to expedite healing of open granulation in 9 patients. Analysis of the results of different treatment strategies revealed that if debridement was accomplished within 20 days of the initial cardiac procedure, 76% of the patients could be successfully treated with closed antibiotic irrigation. Conversely, if treatment was delayed for longer than 20 days, 81% of the patients were treated with open granulation (p less than 0.001). Also noted was an inverse relationship between the serum blood urea nitrogen (BUN) level and the success rate of initial treatment with closed antibiotic irrigation. Patients with a serum BUN level of less than 40 mg/dl at the time of debridement had a 90% success rate as opposed to a success rate of 38% when the BUN level was 40 mg/dl or greater. The data presented suggest the following conclusions. Early diagnosis is crucial to successful treatment of sternal wound infection. When diagnosis can be established within 20 days, 80% of infections can be eradicated by the simple approach of debridement and closed antibiotic irrigation. When diagnosis is delayed, however, prompt debridement followed by muscle flaps is the procedure of choice. Open granulation alone, while successful, unnecessarily prolongs the hospital course. PMID- 4037914 TI - Thromboembolism in patients with aortic porcine bioprostheses. AB - Thromboembolism was prospectively studied in 215 patients who survived aortic valve replacement with porcine bioprostheses. All patients were anticoagulated with warfarin sodium during the first 3 postoperative months. Thereafter, 80 patients received aspirin (325 or 650 mg per day) and 135 received no antiplatelet or anticoagulant drugs. The two groups of patients were similar. Thromboembolic complications were carefully searched for during the follow-up interviews. Patients were removed from the study after a thromboembolic event unless there was no change in their management. The follow-up ranged from 6 to 80 months (mean, 36 months). The linearized thromboembolic rate in patients on a regimen of aspirin was 1.3% per patient-year and in patients not taking aspirin, 5.2% per patient-year (p less than 0.02). Replacement of the ascending aorta and patch enlargement of the aortic annulus with a Teflon graft were identified as significant risk factors for thromboembolism in patients with aortic porcine bioprostheses. These findings indicate that patients with aortic porcine bioprostheses should receive aspirin, especially if they also had replacement of the ascending aorta or patch enlargement of the aortic annulus with a Teflon graft. PMID- 4037915 TI - Hemodynamic evaluation of the integral monostrut Bjork-Shiley prosthesis in the aortic position. AB - Between May, 1983, and November, 1984, the new integral monostrut Bjork-Shiley prosthesis was used for aortic valve replacement in 62 patients. The prosthesis is machined from a solid piece of cobalt alloy and has no welded joints. The traditional U-shaped outlet strut has been replaced by a projecting metal finger that holds the disc in place. The disc opens to 70 degrees and is convexoconcave. Successful transseptal heart catheterization was performed in 23 patients an average of 6 months following operation to evaluate the hemodynamic performance of the prosthesis. The mean peak-to-peak gradient was 7.73 +/- 7.49 mm Hg (+/- standard deviation). In five valves it was 0, and in only three was it higher than 15 mm Hg. Significant peak gradients were directly related to the valve index (valve area/body surface area). Mean systolic gradient at rest was 12.7 +/- 6.27 mm Hg and did not increase after exercise. Effective orifice areas were adequate, and the discharge coefficient ranged from 0.77 for the 21-mm prosthesis to 0.48 for the 29-mm prosthesis. Minimal regurgitation, which was washed out on the next systole, was observed with all sizes of the prosthesis. Disc opening was maximal (70 degrees) in all but one of the observed instances. Longer clinical follow-up is required, but the new integral monostrut Bjork-Shiley prosthesis, with its important design changes and excellent hemodynamic performance, appears to be a promising aortic valve substitute. PMID- 4037916 TI - Complications of ascending aortic intraaortic balloon pump cannulation. AB - Choice of a route of cannulation for intraaortic balloon counterpulsation during cardiopulmonary bypass is related to accessibility. In those patients in whom it is impossible to pass the intraaortic balloon pump (IABP) into the common femoral artery, ascending aortic cannulation is a rapid and direct method of insertion. Eight patients are described in whom ascending aortic IABP cannulation was undertaken to enable weaning from cardiopulmonary bypass after cardiac surgical procedures. The following problems were encountered: graft infection, aberrant cannulation of the left subclavian artery, left coronary artery embolism, and inability to close the sternum due to mechanical tamponade. A technique is described for insertion of the IABP using a polytetrafluoroethylene (Impra) graft and closed-chest decannulation. Although considerable morbidity and mortality are associated with ascending aortic cannulation, it is simple, fast, and effective, and should be considered for all patients requiring postoperative IABP support in whom peripheral vascular disease makes access difficult. PMID- 4037917 TI - Malignant superior vena cava obstruction reconsidered: the role of diagnostic surgical intervention. AB - The cases of 42 patients with malignant superior vena cava (SVC) obstruction were reviewed to evaluate clinical dogmas of prohibitive risk for invasive diagnostic procedures and need for urgent radiotherapy. Thirty-nine had carcinoma (35, bronchogenic and 4, other), and 3 had lymphoma. Lung cancer histology was squamous cell in 11, adenomatous in 10, large cell in 7, and small cell in 7. The SVC obstruction was always symptomatic, usually causing facial or cervical swelling, but there was no instance of SVC obstruction causing life-threatening problems such as cerebral or laryngeal edema. Twenty-two patients underwent bronchoscopy (11 flexible and 11 rigid) prior to radiotherapy without respiratory complications, and diagnostic tissue was obtained in 8. Also prior to radiotherapy, 29 invasive diagnostic procedures were performed: thoracotomy (1), mediastinotomy or mediastinoscopy (11), supraclavicular or scalene node biopsy (15), and percutaneous lung needle biopsy (2). Neither excessive blood loss nor serious complications occurred, and diagnostic tissue was obtained in 22 patients who received individualized therapy. Eight patients had urgent radiotherapy, which delayed diagnosis and specific therapy for two weeks to 6 months. For the 33 patients who underwent radiotherapy after development of the SVC obstruction, the obstruction clinically resolved spontaneously within fourteen days, independently of whether radiotherapy was begun immediately or was delayed. Median survival was 5.0 months and was not influenced by the dose or timing (early or late) of radiotherapy. We reached the following conclusions. First, although a grim prognostic sign, SVC obstruction is rarely life-threatening and typically resolves spontaneously, probably by development of venous collaterals.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4037918 TI - Pulmonary resection in patients after pneumonectomy. AB - In 15 patients with a previous pneumonectomy (eight on the right and seven on the left), a new "lesion" developed in the remaining lung. Fourteen had the pneumonectomy for carcinoma (13 men and 1 woman), and 1 woman had a pneumonectomy for blastomycosis. At the second operation (4 months to 16 years after the pneumonectomy), limited resection of a primary or metastatic malignancy was done. The excision ranged from lobectomy to multiple wedges. One patient died on the sixth postoperative day, presumably a cardiac death. Eight patients died 2 to 33 months postoperatively. Six patients are now living: 3 have no evidence of disease (18, 35, and 70 months), and 3 have recurrent disease (26, 41, and 73 months). There is evidence that pulmonary resection after pneumonectomy is feasible with a low operative mortality and that resection of these "secondary" tumors can result in prolonged, worthwhile survival. PMID- 4037919 TI - Late paraplegia as a consequence of intraaortic balloon pump support. AB - There have been several reports of paraplegia after intraaortic balloon counterpulsation in the surgical literature. In each instance, the paraplegia occurred during the period of counterpulsation support. We describe a patient in whom late paraplegia occurred three days after the removal of an intraaortic balloon catheter. PMID- 4037920 TI - Revascularization without embolization: coronary bypass in the presence of a calcified aorta. AB - The densely calcified ascending aorta presents a formidable challenge to the cardiac surgeon. Clamping such an aorta in the patient requiring myocardial revascularization may result in catastrophic cerebral embolism and mar an otherwise successful surgical outcome. Myocardial revascularization using ventricular fibrillation and hypothermia without aortic cross-clamping in 3 patients with severely calcified aortas is described. PMID- 4037921 TI - Management of chylothorax. PMID- 4037922 TI - Traumatic transection of thoracic trachea. PMID- 4037923 TI - [Medical care for pensioners in the framework of the RIVIZ (National Institute of Illness and Disability Insurance)]. PMID- 4037924 TI - [Recommendations from the Superior Council of Public Health on alcohol consumption and its consequences for drinkers, their families and society]. PMID- 4037926 TI - [Health guidance and education in schools. Possibilities and limitations]. PMID- 4037925 TI - [Part-time work and absenteeism in female workers]. PMID- 4037927 TI - [Monitoring of influenza in Belgium, 1982-1983, 1983-1984]. PMID- 4037928 TI - Some statistical aspects of viral vaccine control. Establishment of an acceptance criterion for potency. PMID- 4037929 TI - Skeletal muscle aging in the hind limb of the old male Wistar rat: inhibitory effect of hypophysectomy and food restriction. AB - By age 1 100 days (37 mth) hind leg paralysis was found in 50% of ad libitum fed (control) male Wistar rats, but only 10% of food restricted rats and no hypophysectomized rats of that age had this disease. Gastrocnemius muscle weight declined at a faster rate than whole body weight in old ad libitum fed rats but not in old hypophysectomized or food restricted rats. Light microscopic and ultrastructural changes were studied in the muscles of the hind limbs of 11 control, 5 food-restricted and 5 hypophysectomized rats aged 805 to 1 307 days. Light microscopic changes in muscles involved progressive degeneration demonstrated by the accumulation of adipocytes and degenerative inclusion bodies. The main ultrastructural changes were associated with myofibrillar breakdown. In addition there was thickening of the basal lamina around blood capillaries. However, muscle from hypophysectomized and food restricted rats of the same age range as controls possessed normal morphology with reduced thickening of the capillary basal lamina. PMID- 4037930 TI - A one-year follow-up of patients discharged from geriatrics and general medical units in Wales. AB - A random sample of patients aged 65 yr and over, admitted as emergencies to the specialties of geriatrics and general medicine in Wales were interviewed 3 and 12 mth after discharge using a postal questionnaire. The characteristics of patients, the preparation they received for discharge and the use made of community services were recorded as were mortality, functional capacity and rehabilitation. Overall geriatrics patients were better prepared for discharge, were given a higher level of service provision and had a more favourable outcome than the general medical patients. PMID- 4037931 TI - Aging in vivo and neuraminidase treatment of rat erythrocytes and their sequestration by the isolated perfused rat liver. AB - The isolated perfused rat liver as a model for phagocytosis leaves the specific arrangement of macrophages in the original tissue structure intact. Therefore phagocytosis may occur under terms closely approaching physiological conditions. Separation of rat erythrocytes according to their density in 13% young, 75% mature and 12% old cells permits the establishment of differences in the mean cellular volume (MCV), mean cellular hemoglobin concentration (MCHC) and content of N-acetylneuraminic acid per red blood cell (NANA/RBC). Perfusion of these fractions does not result in significant differences of sequestration of the isolated liver. Enzymatic release of 90% of membrane-bound sialic acid causes a significant increase of 20% in the elimination of erythrocytes from the perfusate. Treatment with neuraminidase is a trigger for sequestration either by adherence or by complete phagocytosis. Incubation of neuraminidase-treated erythrocytes with plasma does not increase the removal rate of cells during perfusion. PMID- 4037933 TI - Serum creatine kinase activity in the elderly following a stroke. AB - A serial measurement of serum creatine kinase (CK) activity and its isoenzymes were made in elderly patients following an acute stroke. Seven out of ten patients had elevated CK levels. The maximum concentration was observed between 12-24 h and the level returned to normal within 84 h after a stroke. They all had positive skeletal (MM) muscle isoenzyme, and in only one patient heart (MB) isoenzyme was detected. None of them had positive brain (BB) isoenzyme. Measurement of serum CK activity will possibly provide guidance in the management of patients having recently suffered a stroke. PMID- 4037932 TI - Age-related changes in plasma lipid levels and tissue lipoprotein lipase activities of Fischer-344 rats. AB - Fischer-344 rats of 6, 12, 18, 21 and 24 mth of age were investigated. The data were collected from groups of rats ranging from 5-10 rats per age group. Modest age-related increases were noted in body weight, plasma triglycerides, total cholesterol and free (unesterified) cholesterol. Much more significant changes were noted in tissue lipoprotein lipase activities where the adipose tissue lipases declined sharply (r = -0.90, P less than 0.0001; r = -0.86, P less than 0.0001) and the muscle tissue lipases decreased moderately (r = -0.86, P less than 0.0001; r = -0.58, P less than 0.0001) with age. These observed trends suggest that enzymatic parameters, specifically tissue lipoprotein lipase activities, may be considerably more accurate indicators of age-related physiological changes than levels of plasma lipids such as cholesterol and triglyceride. PMID- 4037934 TI - Relationship between gamma-irradiation, life span, metabolic rate and accumulation of fluorescent age pigment in the adult male housefly, Musca domestica. AB - The patterns of fluorescent age pigment (FAP) accumulation in response to gamma irradiation were examined in adult male houseflies under conditions of relatively high and low levels of physical activity. Flies were exposed to 0, 20, 40, and 66 kR and their level of physical activity was altered by permitting or restricting flight activity. Under conditions of high activity the mean life span of flies exposed to 20 kR and 40 kR was greater than in the controls. The mean life span of high activity flies exposed to 66 kR and all groups of low activity irradiated flies was less than the control life span. The force of mortality as indicated by Gompertz slope was greater in high activity controls than in unirradiated flies maintained under low activity conditions. Gompertz slope was similar in corresponding high and low activity groups exposed to radiation. Radiation decreased the rate of FAP accumulation in high activity groups, but increased the rate of FAP accumulation under low activity conditions. The low activity control and low activity flies exposed to 20 kR had a lower FAP accumulation than the corresponding high activity groups at 14 days of age. At this age, low activity groups of flies exposed to 40 kR and 66 kR had concentrations of FAP that were similar to the corresponding high activity groups. These results indicate that radiation exposure decreased longevity by causing damage rather than by increasing the rate of aging. PMID- 4037936 TI - More reports from the front in war against cancer. PMID- 4037935 TI - Memory impairment in the elderly: a three-year follow-up. AB - A 3-yr follow-up study on the trend of memory performance in 9 elderly subjects with selective memory defects, which was carried out in an attempt to clarify the evolution of the disorder, revealed marked worsening of sensory visual memory, retention capacity and recent memory. No other mental function was compromised. The results of this study suggest that the onset of a selective memory defect in the elderly is not necessarily the expression of a demential amnestic syndrome, but rather the manifestation of a senile brain deterioration limited to the anatomo-functional memory system. PMID- 4037937 TI - On classifying cancers while treating patients. PMID- 4037938 TI - Urine cultures and long-term indwelling catheters. PMID- 4037939 TI - Factors influencing erythrocyte sedimentation in patients with chronic renal failure. AB - Erythrocyte sedimentation was studied in stable patients with chronic renal failure free of complicating illnesses. The mean (+/- SD) Westergren erythrocyte sedimentation rate was 49 +/- 26 mm/hr in patients not receiving dialysis and 60 +/- 33 mm/hr in patients receiving hemodialysis. Both values are significantly higher than normal. Because anemia accelerates the Westergren determination, we restudied the patients with the zeta sedimentation ratio (ZSR), a method unaffected by hematocrit. In nine patients not receiving dialysis and 49 patients receiving hemodialysis, the ZSR was significantly higher than normal. The ZSR correlated positively with plasma fibrinogen concentration. Recombination experiments showed that the abnormal factor accelerating erythrocyte sedimentation was a constituent of plasma. Thus, erythrocyte sedimentation is accelerated in stable patients with chronic renal failure and a plasma factor, probably fibrinogen, is responsible. An elevated erythrocyte sedimentation rate in this population lacks diagnostic usefulness. PMID- 4037940 TI - Predicting the likelihood of hemorrhage in patients with stroke. AB - To identify those clinical findings that independently help differentiate intracranial hemorrhage from cerebral infarction, we studied patients who were admitted to a hospital with acute focal neurologic deficits after strokes during a 17-month period. The predictive strength of a decision-making aid incorporating these findings was then assessed by studying patients who were admitted to a different hospital after experiencing strokes. The decision-making aid stratified the patients into groups having probabilities of intracranial hemorrhage ranging from 5% to 67%. The results of this study may facilitate more discriminating test selection during the early evaluation of patients who have had strokes. PMID- 4037941 TI - Cutaneous manifestations of sarcoidosis. Relationships to other organ system involvement, abnormal laboratory measurements, and disease course. AB - The charts of 329 patients with sarcoidosis were reviewed to determine if there were significant associations between the presence of sarcoidosis skin lesions and other abnormalities. Sixty-four patients had either biopsy specimen documented cutaneous granulomata or erythema nodosum (EN). Respiratory symptoms occurred in 41% of patients with skin lesions compared with 63% of patients with sarcoidosis without skin lesions. Among patients with skin lesions other than EN, splenomegaly occurred in 38%, hepatomegaly in 32%, and lymphadenopathy in 31% compared with 10%, 11%, and 56%, respectively, for patients with sarcoidosis without skin lesions. Thirty-two percent of patients with EN had progressive disease compared with 72% of patients with skin lesions other than EN; however, improved prognosis with EN was limited to white patients. PMID- 4037942 TI - Significant metabolic acidosis induced by acetazolamide. Not a rare complication. AB - Blood gas and serum electrolyte levels were measured in 27 elderly patients (mean age +/- SD, 63.3 +/- 13.5 years) who were receiving acetazolamide (250 to 1,000 mg/day) for glaucoma. Eleven glaucomatous patients (mean age, 69.1 +/- 7.4 years) who were not receiving acetazolamide served as a control group. In the acetazolamide-treated group, four patients (14.8%) had mild acidosis (7.29 greater than pH less than or equal to 7.31), ten (37%) had moderate acidosis (7.20 greater than pH less than or equal to 7.29), and one patient (3.7%) had severe acidosis (pH, 7.15). None of the patients in the control group had acidosis. It is concluded that moderate metabolic acidosis of potential clinical significance is common among glaucomatous elderly patients who receive acetazolamide. The exact clinical significance of our observations is yet to be determined. PMID- 4037943 TI - Massive skeletal muscle invasion by lymphoma. AB - Three patients had diffuse enlargement of skeletal muscle of the thigh as the result of infiltration by diffuse large-cell lymphoma. One case presented de novo as diffuse lymphoma, but the other two had previous diagnoses of nodular lymphoma and Hodgkin's disease. Computed tomographic scanning disclosed an enhancing mass in the thigh with infiltration of skeletal muscle groups; abnormal medullary cavities were noted in the adjacent long bones. Muscle biopsy established the diagnosis in two of the patients. PMID- 4037944 TI - Auscultatory percussion of the urinary bladder. AB - A volumetric study of the bladder was done in 170 adult male patients examined by auscultatory percussion. The upper border of the urinary bladder was defined and measured in reference to the symphysis pubis to gauge urinary volume. The findings were correlated with the urinary volumes obtained after the bladder had been emptied by voiding in 90 patients without urinary tract disease and in 42 patients who required catheterization. With a bladder level less than 2 cm, none of the patients had a full bladder or a urinary volume of 250 mL. Of the 55 patients with bladder levels of 3 cm or more, 53 patients had full bladders. Catheterizations were timely and avoided frequent and unnecessary catheterization. Residual urinary volumes estimated by auscultatory percussion in 12 patients with obstructive uropathy and 26 patients studied with indwelling catheters correlated closely with the catheterized urinary volumes. Full bladders, obstructive uropathy, and malfunctioning indwelling catheters were readily detected. PMID- 4037945 TI - Identification of community flour mills as the source of lead poisoning in West Bank Arabs. AB - Following the discovery of severe lead poisoning in members of several households in a West Bank village, studies were carried out to establish the magnitude of the problem in the community and to identify the source of lead poisoning. Forty three patients with Centers for Disease Control risk group IV lead poisoning were identified and treated in three villages within a radius of about 10 km of each other. The prevalence of increased lead burden among 563 schoolchildren aged 10 to 18 years was 19% for Centers for Disease Control risk groups I and II and 11% for groups III and IV. A survey of potential sources excluded all items, except for locally ground flour, which was heavily contaminated in all affected households. Examination of community flour mills revealed that, in contrast to unprocessed grain, freshly ground flour contained large amounts of lead originating from lead fillings employed to fasten the housing of the driveshafts to the millstones. Systematic screening of 146 community stone mills in 92 West Bank villages showed significant lead contamination of flour in 33 mills (23%). In all cases, the source of lead contamination was identical. As methods of milling in the area are similar, a prompt investigation of this potential source of lead poisoning in other near-Eastern countries is indicated. PMID- 4037946 TI - Validity of urinary catheter specimen for diagnosis of urinary tract infection in the elderly. AB - Twenty elderly nursing home patients with long-term indwelling bladder catheters were studied to evaluate the validity of the microbiology of urine samples obtained from catheters that had not been changed for at least 30 days. Paired urine samples from "old" catheters and newly inserted catheters were compared for quantitative and qualitative microbiology. Urine microbiology for old catheters was highly sensitive but had poor specificity. PMID- 4037947 TI - Recurrent leg symptoms following deep vein thrombosis. A diagnostic challenge. PMID- 4037948 TI - Exclusion bias and the false relationship of reserpine and breast cancer. AB - Although reserpine has an important role in treating patients with hypertension, its appeal was sharply reduced a decade ago when an alleged relationship to breast cancer was reported in case-control studies. Since the relationship was not confirmed in subsequent research and analyses, the original association is now regarded as erroneous. Since patients with cardiovascular disease were rejected as possible controls in the original reserpine-breast cancer case control study, we suspected that the false association may have been produced by a phenomenon called exclusion bias. This bias can arise in case-control studies if patients with a particularly high (or low) rate of prior exposure to the alleged etiologic agent are excluded from the selection of either cases or controls, but not from both. To test that suspicion, we recapitulated the original study, in another medical setting. The cases were 257 women with breast cancer; and the controls were 257 hospitalized women matched according to date of admission, age, and race. The overall data showed no association between reserpine and breast cancer (odds ratio [OR] = 1.1), but when we excluded 101 women with cardiovascular disease from the control group, the OR rose to 2.5. The results suggest that exclusion bias played an important role in creating the false association between reserpine and breast cancer. PMID- 4037949 TI - The Selvester QRS scoring system for estimating myocardial infarct size. The development and application of the system. PMID- 4037950 TI - Insidious onset of fatigue, dyspnea, and leg edema. PMID- 4037951 TI - Ventricular tachycardia in acute rheumatic fever. AB - A 19-year-old man presented with fever, migratory polyarthritis, and palpitations; a diagnosis of acute rheumatic fever was made. Twenty-four-hour ambulatory cardiac monitoring (Holter) performed during the patient's hospitalization revealed ventricular tachycardia. Although disturbances in cardiac conduction and rhythm are common during the acute phase of rheumatic fever, malignant ventricular arrhythmias, to our knowledge, have not been described. Recognition of this occurrence emphasizes the need for continuous cardiac monitoring in selected patients. PMID- 4037953 TI - Behcet's syndrome complicated by cutaneous leukocytoclastic vasculitis. Response to prednisone and chlorambucil. AB - Traditionally described as a triad consisting of recurrent aphthous stomatitis, genital ulcerations, and uveitis, Behcet's syndrome is now recognized as a multisystem disease with protean manifestations. We studied a patient with chronic recurrent migratory superficial thrombophlebitis and marked cutaneous hyperreactivity (pathergy) who developed leukocytoclastic vasculitis with recalcitrant leg ulcerations nine years after the onset of his illness. Although he was treated with topical and systemic antibiotics for presumed bacterial superinfection, cutaneous ulcerations continued to develop and enlarge; only after prednisone therapy was begun was there a dramatic response with complete resolution. Despite high-dose prednisone therapy, the pathergy test remained markedly positive; however, no new skin ulcerations appeared. PMID- 4037954 TI - Portal-systemic myelopathy after portacaval shunt surgery. AB - Portal-systemic myelopathy is a rare complication of surgically created or spontaneous portal-systemic shunts in patients with chronic liver disease. We treated two patients with this entity, both of whom had undergone portacaval shunt operations. PMID- 4037955 TI - Role of angiotensin in lethal cerebral hypoperfusion during treatment of acute hypertension. AB - A 23-year-old man developed lethal cerebral hypoperfusion associated with angiographically demonstrable cerebral arterial spasm while being treated for acute angiotensinogenic hypertension due to a traumatic coarctation of the aorta. This complication occurred even though the treatment maintained his blood pressure at normotensive to mildly hypertensive levels, without producing more than rare and fleeting periods of hypotension. To explain this enigmatic development, we propose that the high concentration of angiotensin II in the blood constricted the cerebral arteries and thus prevented adequate cerebral autoregulation when his blood pressure was lowered by drug therapy. PMID- 4037952 TI - Fatal acute respiratory failure after vinblastine-mitomycin therapy in lung carcinoma. AB - The occurrence of pulmonary toxic reaction due to vinblastine sulfate alone or in combination with drugs other than mitomycin is not known. Acute respiratory distress is a rare phenomenon in patients receiving both chemotherapeutic agents. Two cases of fatal acute respiratory failure due to pulmonary edema occurred in patients receiving vinblastine-mitomycin for non-small-cell carcinoma of the lung. In view of the unpredictability of the reaction, observation of patients receiving this combination therapy is recommended. PMID- 4037956 TI - Dipyridamole-thallium imaging. PMID- 4037957 TI - Fractional excretion of chloride in prerenal azotemia. PMID- 4037958 TI - Lactate dehydrogenase isozyme and hypothyroidism. PMID- 4037959 TI - Pericarditis and the sick sinus syndrome. PMID- 4037960 TI - A surgical approach to achalasia of the esophagus. PMID- 4037961 TI - Ceramic prosthesis of the cervical vertebra in metastatic tumor of the spine. PMID- 4037962 TI - [Pyogenic liver abscess]. PMID- 4037963 TI - Retrocollicular arachnoid cyst with the inferior sagittal sinus anomaly and the corpus callosum dysgenesis. PMID- 4037964 TI - Visual field defects and the size and shape of pituitary adenomas. PMID- 4037965 TI - [Surgery of a left atrial myxoma]. PMID- 4037966 TI - Thrombosed Lillehei-Kaster mitral prosthesis. PMID- 4037967 TI - [Calcified brain abscess. Report of a case]. PMID- 4037968 TI - [Intrapulmonary tunnel repair for the anomalous origin of the left coronary artery from the pulmonary artery: report of a case]. PMID- 4037969 TI - Pelvic deformity after simple pelvic osteotomy. PMID- 4037970 TI - Improvement of femoral head coverage by Chiari osteotomy. PMID- 4037971 TI - [Experimental studies on the hemodynamics of the gastric tube for esophageal reconstruction]. PMID- 4037972 TI - [Microwave surgery for splenic preservation: an experimental study]. PMID- 4037973 TI - [Animal abuse and other illegal acts in animal care]. PMID- 4037974 TI - [Problems concerning pedestrians run over while in prone position]. AB - By the analysis of 54 traffic accidents involving prone, run-over people it is shown that the vast majority were drunken males who lay on the road during the night and were there driven over. There are many reasons for the "lying on the road" including, falling due to sickness, voluntary lying for suicide, falling of lying due to an alcoholic condition. For evidence respectively exclusion a previous accident, the clothing must be precisely examined for trace evidence (textile changes, transfer of paint, glass fragments, tyretread patterns, skidmarks from shoes). An analysis of skin, bones and internal organs indicates the cause of the injuries (driving into, throwing on to, throwing off and rolling over). PMID- 4037975 TI - [Heroin deaths. Cadaver disposal--defensive cadaver dismemberment]. PMID- 4037976 TI - [Unusual injuries caused by blows with a sash saw]. AB - A 62-year old man was found killed by multiple blows against the face and head; near the victim a hammer with broken grip, a bended saw (weight 142 g), and in the possession of the doer two hatchets. Some straigt, parallel, horizontal wounds in the face with smooth lips and straigt incisions of the maxilla first were interpreted as violations by hatchet. The culprit confessed attacks by hammer and saw, but not by hatchet. Experimental blows with a saw like the used on the leg of a corpse showed an unexpected result: it was possible to produce wounds of the soft-tissues and the bone similar to those by hatchets. PMID- 4037977 TI - [Evaluation of cuticula structure of the human hair]. AB - The cuticula is influenced by inner and outer factors. Through the combination of these factors the cuticula takes forms, which can be individual in same cases. But in most cases the marks of the cuticula are not enough specific to attach a hair to an individual person. Therefore the hair investigation has to be done in combination with other marks of the hair. PMID- 4037979 TI - Nature and linkage type of fatty acids present in lipopolysaccharides of phase I and II Coxiella burnetii. AB - The constituent fatty acids of lipopolysaccharides (LPS) of Coxiella burnetii (phase I and II) were qualitatively and quantitatively analysed by combined gas liquid chromatography/mass spectrometry. The total fatty acid content (per mg LPS) was determined as 90.0 nmol (2.3 wt%) for LPS of phase I cells (LPS I) and 179.1 nmol (4.8 wt%) for LPS of phase II cells (LPS II). Of the 24 different acyl residues characterized (12 to 18 carbon atoms), nine were 3-hydroxy fatty acids (normal, iso- and anteiso-branched) which quantitatively predominated. All 3 hydroxylated fatty acids were found to possess the (R)-configuration, to be exclusively amide-linked and to be acylated at their 3-hydroxyl group. Ester linked nonhydroxylated fatty acids (normal, iso- and anteiso-branched) were present but ester-bound 3-hydroxy- or 3-acyloxyacyl residues were lacking from C. burnetii LPS I and LPS II. As the major acyl group (R)-3-(12-methyl tetradecanoyloxy)-12-methyl-tetradecanoic acid was identified. Our results show that the complex fatty acid spectrum of C. burnetii differs considerably from that of LPS of other Gram-negative bacteria. They further suggest an enormous heterogeneity of the lipid A component of C. burnetii LPS I and LPS II. PMID- 4037978 TI - Isolation of L8 and L8S8 forms of ribulose bisphosphate carboxylase/oxygenase from Chromatium vinosum. AB - The enzyme ribulose bisphosphate carboxylase/oxygenase has been purified from Chromatium vinosum. When an extract is subjected to centrifugation at 35,000 X g in the presence of polyethylene glycol (PEG)-6000 and the supernatant is treated with 50 mM Mg2+ and the precipitate is then fractionated by vertical centrifugation into a reoriented sucrose gradient followed by chromatography on diethylaminoethyl (DEAE)-Sephadex A50, the resultant enzyme contains large (L) and small (S) subunits. Alternatively, centrifugation of extracts at 175,000 X g in the presence of PEG-6000 followed by fractionation with Mg2+, density gradient centrifugation, and chromatography on DEAE-Sephadex A50 yields an enzyme free of small subunits. The two forms have comparable carboxylase and oxygenase activities and have compositions and molecular weights corresponding to L8 and L8S8 enzymes. The amino acid compositions of L and S subunits are reported. The L8S8 enzyme from spinach cannot be similarly dissociated by centrifugation at 175,000 X g in the presence of PEG-6000. PMID- 4037981 TI - Effect of 2-deoxyglucose, alpha-methylglucoside, and glucosamine on aflatoxin production by Aspergillus parasiticus. AB - The effects of 2-deoxyglucose (2-DOG), alpha-methylglucoside (alpha-MG), and glucosamine (GA) on aflatoxin production by Aspergillus parasiticus were studied using conidia-initiated and replacement cultures. In conidia-initiated, 2-DOG, alpha-MG, and GA supported varying amounts of growth when employed as sole carbon sources. In both conidia-initiated and replacement cultures, 2-DOG, but not alpha MG nor GA, as sole carbon sources support toxin formation. None of the compounds inhibited aflatoxin production when used in combination with glucose. It appears that neither 2-DOG, alpha-MG, nor GA can be considered nonmetabolizable analogs of glucose in A. parasiticus. PMID- 4037980 TI - A sodium ion gradient as energy source for Peptostreptococcus asaccharolyticus. AB - The determination of enzymatic activities in cell-free extracts of Acidaminococcus fermentans and Peptostreptococcus asaccharolyticus led to a refined scheme for the pathway of glutamate fermentation via (R)-2 hydroxyglutarate to acetate and butyrate. From the ratio of these products the amount of ATP generated by substrate level phosphorylation was calculated. Growth experiments with the organisms including Clostridium symbiosum and Clostridium tetanomorphum indicated that a sodium gradient contributed additional energy for growth. The high growth yields found in organisms containing the biotin dependent sodium pump glutaconyl-CoA decarboxylase could be reduced by the sodium ionophor monensin. In P. asaccharolyticus energy equivalent up to 0.6 mol ATP per mol of glutaconyl-CoA decarboxylated was conserved via the Na+ gradient. The data may explain the growth promoting effects of monensin in cattle. PMID- 4037982 TI - Melanin biosynthesis and the metabolism of flaviolin and 2-hydroxyjuglone in Wangiella dermatitidis. AB - Melanin biosynthesis in the human pathogen Wangiella dermatitidis was inhibited by tricyclazole, causing pentaketide melanin metabolites to accumulate in the cultures. One of these metabolites, scytalone, was racemic and thus different than the (+)-enantiomer from Verticillium dahliae. An albino mutant of W. dermatitidis metabolized scytalone to a pigment ultrastructurally identical to wild-type melanin. Cell-free homogenates of the wild type carried out typical reductive and dehydrative reactions with known melanin intermediates and the reductive reactions were inhibited by tricyclazole. Other reductive and dehydrative reactions that utilize flaviolin and 2-hydroxyjuglone were studied anaerobically with homogenates from both the wild type and the albino mutant. The homogenates converted flaviolin to 5-hydroxyscytalone and products identical to those obtained from 2-hydroxyjuglone. The albino, in culture, carried out the same reactions with 2-hydroxyjuglone but metabolized flaviolin to a number of unknown colored products apparently through oxidative reactions. Similarities between the melanin pathway and the flaviolin and 2-hydroxyjuglone branch pathways are discussed and tricyclazole is shown to inhibit reductive reactions with naphthols in the three pathways. PMID- 4037983 TI - A newly-isolated marine methanogen harbors a small cryptic plasmid. AB - Of 21 recently isolated strains of methanococci, one was found to harbor a small, cryptic, low copy number plasmid. Reproducible recovery was achieved by alkaline lysis of cells pretreated with proteinase K in an osmotically stabilizing buffer. The plasmid was found to contain a single AvaI site. No homology was detected between the plasmid and DNA from any of the other new strains or from five known species of methanococci. PMID- 4037984 TI - Thought disorder in children at risk for psychosis. AB - The Thought Disorder Index, which has been shown to be a reliable and valid measure of the degree of thought disorder in adult psychotic patients, was used to assess thought disorder in children. Normal children aged 5 to 16 years, hospitalized psychotic children, children hospitalized for nonpsychotic behavioral problems, and children born to a psychotic mother (high-risk) were tested. In the normal sample, thought disorder decreases with age. The level of thought disorder in psychotic children and high-risk children was about three times higher than that of the normal children, whereas the level of thought disorder of the nonpsychotic hospitalized children was no different from that of the normal children. The study also detected differences in the kinds of thought disorder that characterize the psychotic and high-risk groups vs the other children. The presence of thought disorder may be thought of as a useful indicator of the diathesis for functional psychosis. The Thought Disorder Index merits selection as a tool for investigating thought disorder as a potential precursor variable in studies of children at risk for schizophrenia and manic depressive illness. PMID- 4037985 TI - Brain-stem dysfunction in autism. Results of vestibular stimulation. AB - Responses to vestibular stimulation can, under well-controlled experimental conditions, provide a measure of brain-stem function. Autistic children had significantly longer time constants during the primary nystagmus response and significantly fewer beats during the secondary response than normal children when stimulated with constant angular acceleration in complete darkness. These findings could not be attributed to gross differences in arousal, to developmental retardation, to associated clinical conditions, or to either the influence of vision or habituation. Rather, they are suggestive of a neurophysiologic dysfunction, perhaps involving the brain stem, and may be an expression of the process that underlies those autistic behaviors that suggest faulty modulation of sensory input and motor output. Brain-stem centers modulate both general sensory input and motor excitation and may play a role in the elaboration of the more complex adaptive and motivated behaviors that are also disturbed in autism. PMID- 4037986 TI - Hyperactive children have grown up. What have we learned about what happens to them? PMID- 4037987 TI - Hyperactive boys almost grown up. I. Psychiatric status. AB - We report a prospective longitudinal study of 101 male adolescents (ages 16 to 23 years) who had been diagnosed hyperactive in childhood (ages 6 to 12 years), compared with 100 normal controls. The DSM-III diagnoses were made blind to group membership. Information was obtained for 98% of the original cohort. The full attention deficit disorder with hyperactivity (ADDH) syndrome persisted in 31% of the probands vs in 3% of the controls. The only other two conditions that distinguished the groups significantly were conduct and substance use disorders. These disorders aggregated significantly among the probands with continued ADDH. The results indicate that the greatest risk factor for the development of antisocial behavior and drug abuse is the maintenance of ADDH symptoms. Substance use disorders followed the onset of conduct disorder in the overwhelming majority of the cases. PMID- 4037988 TI - Early parental separation and adult depression. AB - In a comparison with 300 matched controls, significantly more of 300 patients with nonendogenous depression had experienced permanent separation (not due to death) from their mother before both 11 and 17 years of age and significantly more had experienced permanent separation from their father (not due to death) before both 11 and 17 years of age. The results suggest that early permanent separation from mother is a risk factor for nonendogenous depression but occurs in only about 6.7% of these patients before 11 years of age and in about 10% before 17 years of age and early permanent separation from father is also a risk factor for nonendogenous depression and occurs in about 9.3% of these patients before 11 years of age and in about 16.7% before 17 years of age. PMID- 4037989 TI - Affective disorders in referred children and younger siblings of manic depressives. Mode of onset and prospective course. AB - We studied 68 referred juvenile offspring or siblings of adult bipolar patients. Mean age at onset of affective and related disturbances was 15.9 years (range, 6 to 24 years). Although four of the ten prepubertal children had hypomanic features, full-blown manic psychosis did not appear before puberty. In the sample at large, 12 were classified as dysthymic and ten as cyclothymic. Eleven additional subjects with polysubstance abuse, who at onset did not meet criteria for affective disorder, were reclassified as having either a dysthymic or a cyclothymic disorder during follow-up. Of the remaining patients--24 depressive, eight manic, and three mixed state--71% experienced recurrences; mood-incongruent features, present in four cases at onset, recurred in only one patient during subsequent episodes. Overall, half the sample evidenced signs of bipolarity during a mean prospective follow-up period of three years. PMID- 4037990 TI - Cortisol secretion in endogenous depression. I. Basal plasma levels. AB - Plasma levels of cortisol were sampled for 24 hours in 32 endogenously depressed (ED) patients and 72 normal controls who also underwent the dexamethasone suppression test. The ED patients had significantly higher mean 24-hour plasma levels of cortisol (means 24h PC). However, means 24h PC values of subjects in both groups were normally distributed, with a marked overlap between the two. Only seven ED patients had means 24h PC values higher than 2 SDs from the normal mean (greater than 10 micrograms/dL). An abnormal dexamethasone suppression test result was only partially related to basal cortisol levels. The mean plasma level of cortisol between 1 and 4 PM was found to be highly correlated with the means 24h PC value in ED patients, as has been previously reported in normal subjects and patients with various other diseases (in which it also powerfully discriminated between hypersecretors and normosecretors). This finding supports the use of mean cortisol levels between 1 and 4 PM as a reliable and convenient indication of cortisol secretion. PMID- 4037991 TI - Cortisol secretion in endogenous depression. II. Time-related functions. AB - Plasma levels of cortisol were sampled for 24 hours in 32 endogenously depressed (ED) patients and 72 controls to examine mean 24-hour plasma levels of cortisol, intervention in the feedback mechanism of the hypothalamic-pituitary-adrenal system (the dexamethasone suppression test), the circadian rhythm of cortisol secretion and its magnitude, and the ultradian rhythm of cortisol secretion. The main difference in the pattern of cortisol secretion in ED patients, as compared with controls, was in the ultradian rhythm. No acrophase or nadir advance of cortisol secretion in endogenous depression was found when age was controlled, but there was an earlier timing of first secretory episode of cortisol (during night). Only some ED patients have abnormalities in each of the functions studied, and they only partially overlap each other. The results suggest that abnormal cortisol secretion in depression should not be viewed as a monolithic malfunction characteristic of endogenous depression. PMID- 4037992 TI - Do cohort effects influence suicide rates? PMID- 4037993 TI - Conditioning and the origins of psychopathology. PMID- 4037994 TI - [Practical application of logistic function to the growth of experimental tumors]. AB - The properties of the logistic law of growth (Verhulst-Pearl) and a simple method for computing of statistical approximation are described. Two parameters are estimated: the generation rate c and the mortality rate c0, although the real biological processes are of greater complexity. The logistic law is modified by an additional term concerning the prefinal decline in the last life span. To prove the curve fitting to tumour growth by the modified logistic function the total number of Ehrlich ascites tumour cells was measured in 144 mice at 12 different times after inoculation. The accuracy of the curve fitting proved to be very good. Therefore the logistic function modified by an additional term for the final stages, is particularly suited for the characterization of Ehrlich ascites tumour growth and its changes. PMID- 4037995 TI - Some remarks on preinvasive cervical neoplasia--an image analysis study. AB - By means of automated microscope image analysis 5275 normal cells as well as dyscaryotic cells were investigated in cytologic preparations from 53 cervical smears (26 negative cases, 27 positive cases). In this way, visually not conspicuous differences between normal cell populations of positive and negative cases could be demonstrated with multivariate statistic analysis of discriminant features. The examination of this phenomenon in 2910 epithelial cells from tissue sections of portio conizations has shown that the subvisually changed epithelial cells originate from circumscript regions in the margin and surroundings of CIN lesions. The biological role of these changes in the formal genesis of cervical neoplasias has been discussed. PMID- 4037996 TI - Automated microscope image analysis in the cytological tumor diagnostics. Results on borderline-cases of mammary tumors. AB - 50 fine-needle biopsies of mammary tumors (20 medullary carcinomas, 20 fibroadenomas, and 10 false negative judged cases) were studied by automated microscopic image analysis. Eight morphometric and densitometric features of the tumor cell nuclei were determined on Papanicolaou stained smears. It was analyzed whether smears false judged as negative can be rightly allocated as carcinomas by the automated method. The results of this study have shown that it was possible by means of three cell nucleus parameters (standard deviation of the area, mean area ratio, and skewness of the grey value gradient at contours) with 100% correct separation of the unequivocal cytologies into malignant and benign smears to recognize about 90% of the false judged smears rightly as carcinomas. The results are reproducible and can be obtained in a time of 2-5 min per smear. The first results show that the automated microscope image analysis may be a valuable tool in the diagnosis of borderline-cases of mammary tumors. PMID- 4037997 TI - Biochemical and cytological features of diffuse mesotheliomas of the pleura. AB - The malignant mesothelioma was proved by autopsy as cause for death in 55 cases- 42 men and 13 women. 4 men had the tumor without pleural effusion. Transthoracic fine needle biopsy confirmed the suspicion 3 times. The fluids caused by the tumor were exudates 50 times. One fluid was a transudate. Cytological examinations led to the partition into four sections with the following main findings: histiocytes, mesothelial cells also in clusters, tumor cells--21 cases; tumor cells without perceptibility of the matrix--18 cases; cytological empty sediments--8 cases; finding of inflammation--4 cases. The determination of the level of hyaluronic acid in pleural fluids by a colorimetric test proved a malignant mesothelioma in one third of these cases. The synopsis of the named parameters together with clinical dates in general use gives the possibility to put up the diagnosis of the primarily malignant disease of the pleura during lifetime of a patient. PMID- 4037998 TI - [Clinical cancer documentation of the Central Institute for Cancer Research of the Academy of Sciences of the German Democratic Republic, Berlin-Buch--tasks, organization and usefulness]. AB - The Hospital based Cancer Registry working at the Central Institute for Cancer Research, Academy of Sciences of GDR is demonstrated. The paper describes its organization, the data collected, its activities and benefit for research and clinical practice. PMID- 4038000 TI - Is it possible to overcome completely the problem of the poor quality of cancer mortality data? PMID- 4037999 TI - [The problem of occupational cancer in cancer of the nose and the nasal sinuses in patients exposed to sawdust]. AB - The results of a cross-sectional study carried out in seven districts of the GDR and Berlin, capital of the GDR, show a significantly increased number of tumors in male woodworkers. Compared to 13 expected tumors the number of those observed amounted to 62. The most frequent localisation was the ethmoidal sinus; adenocarcinomas dominated histologically. PMID- 4038001 TI - Phagocytosis of collagen by fibroblasts incident to experimental tooth movement. AB - The upper molars of adult Wistar rats were moved lingually by a wire spring for 5 and 9 days. Collagen-containing fibroblasts in the pressure zone caused by the tooth movement were investigated morphologically (forms characterized by type A and type B compartments) and cytochemically (location of acid and alkaline phosphatase activity). The following results were obtained: The distribution of collagen-containing fibroblasts with type A or type B compartments could not be distinguished clearly in either 5-day or 9-day specimens; Acid phosphatase activity was recognized in the Golgi apparatus, lysosomes, and elliptical bodies associated with type B compartments; Alkaline phosphatase activity was positive in the plasma membrane of collagen-containing profiles and in both intracellular and extracellular collagen fibrils. These results suggest that fibroblasts are capable of phagocytosing collagen fibrils in all areas of the cytoplasmic membrane and that digestion of collagen fibrils in fibroblasts may be associated with acid and alkaline phosphatase. PMID- 4038003 TI - Differentiation of red pulp and evaluation of hemopoietic role of human prenatal spleen. AB - Both the development of red pulp and hemopoietic activity in spleen obtained from 62 human embryos and fetuses between 30 days and 20 weeks after ovulation were investigated light and electron microscopically. The spleen develops in the left posterior portion of the dorsal mesogastrium at 35-40 days after ovulation. At the 8th week after ovulation, reticular cells formed a three-dimensional meshwork. Two types of reticular cells (dark and clear reticular cells) were observed in the splenic cord in the 12-13th week after ovulation. Mature hemopoietic cells, mostly of the erythroblastic series, increased in number in the extravascular spaces with the development of the fetus. However, presumptive hemopoietic stem cells or "undifferentiated mononuclear cells" (Fukuda, 1973a) did not appear in the spleen. Moreover, immature hemopoietic cells such as proerythroblasts, myeloblasts and megakaryoblasts could not be detected. Therefore, despite the occurrence of a well-developed reticular cell network, hemopoiesis was judged to have not taken place in human fetal spleen. Macrophages appeared in the spleen at the 8th week after ovulation and increased in number with the the development of the fetus. Phagocytosis of decrepit blood cells proved to be an essential function of the spleen. PMID- 4038002 TI - Visualization of the cerebrospinal fluid drainage into the Galen's vein. AB - Arachnoid granulations are not always present in lower mammals and primate newborns. In order to visualize the route for the cerebrospinal fluid (CSF) to drain into the venous system, horseradish peroxidase (HRP) was injected into the lateral ventricle or cisterna cerebellomedullaris of the mouse and rat. From 30 to 60 min after the commencing of a slow infusion for 15-30 min of 0.05-0.1 ml solution containing 10-20 mg HRP, the mouse, whose skull had been exposed, was dropped into cold acetone at dry ice temperature; other animals were fixed by perfusion with aldehyde solution. The frozen head was dissected in a cryostat kept at -18 degrees C to remove the skull, but leave the dura mater and the falx cerebri. The brain with meninges was cut into 30-45 microns sagittal sections in the cryostat, and processed for peroxidase reaction. The perfusion-fixed brains were used for scanning electron microscopy and for electron microscope observation of the tracer. The reaction product was found within fenestrated venous capillaries of the choroid plexus. The route for the HRP in the CSF to drain into the sinus rectus via the vena choroidea and vena cerebri magna was directly visualized in the mouse. PMID- 4038004 TI - Ultrastructural changes in development and aging of the interrenal cell of the salamander, Hynobius nebulosus. AB - The fine structure of interrenal cells in the salamander, Hynobius nebulosus, from prometamorphic larvae to its adult stage, was observed with electron and light microscopes. In all the animals examined the interrenal cell clusters were located at the medial edge of the ventral surface along the total length of each kidney, suggestive of a primitive nature. In larval salamanders, the interrenal cells contained small to moderate numbers of lipid droplets, and their cytoplasm was filled with a tubular network of smooth endoplasmic reticulum (SER) and numerous mitochondria with tubulo-vesicular cristae. In the adult and young adult salamanders, however, most interrenal cells were filled with lipid droplets, so that both tubular SER and mitochondria were decreased in amount in inverse proportion to the increased lipid droplets. These mitochondria frequently contained a crystalloid structure composed of closely packed tubules which were continuous with the cristae. These findings suggest that the interrenal cells in the larvae are more active than those in the adult or young adult salamanders. In addition, the interrenal cells at the end of metamorphosis contained a greater number of enlarged mitochondria with loosely distributed tubular cristae and with a less dense matrix and more numerous membrane-bounded dense bodies, 0.1-0.3 micron in diameter, than those at the prometamorphic stage. These findings suggest that the cells are their most active at this stage. In the prometamorphic larvae, bundles of filaments frequently occurred in the cytoplasm, especially around the nucleus. These filaments gradually decreased in number with the advance of age, and in young adult salamanders they appeared only occasionally. PMID- 4038005 TI - Ultrastructure of the glomerular corpuscular nerve endings in the subepithelium of human epiglottis. AB - The nerve endings in the subepithelial tissue of the surgically removed human epiglottis were observed by electron microscopy. The nerve varicosities (3-6 microns in diameter) with an accumulation of mitochondria and interconnecting nerve fibers supported by Schwann cells constituted the glomerular corpuscles (50 70 microns in diameter). The processes of the nerve varicosities, containing small clear and large dense cored synaptic-like vesicles, were in contact with basal cells of the stratified squamous epithelium. The glomerular corpuscular nerve endings are presumed to be concerned with low threshold mechanoreceptive functions, such as tactile sensation. PMID- 4038006 TI - Epithelial-mesenchymal interface in the rat mandibular process observed by electron microscopy. AB - Epithelial-mesenchymal interfaces in the stomodeal side of the rat mandibular processes were observed at Theiler's stages 14 and 15, when no epithelial organogenesis could be detected by electron microscopy. At stage 14, the basal lamina was discontinuous. Disintegrated basal lamina-like materials were seen in the epithelial-mesenchymal interface. A number of coated vesicles and smooth vesicles were seen in epithelial cell processes adjacent to the disintegrated basal lamina-like materials. Some epithelial cell processes penetrated into the mesenchymal space through the basal lamina and touched the ectomesenchymal cells. Other epithelial cell processes or satellite cell bodies protruded into the mesenchymal space, but were covered with basal laminae. At stage 15, the basal lamina was smooth and continuous with partial duplications. Ruthenium red positive anionic sites were distributed in the basal lamina and on thin filaments underneath the basal lamina. At stage 15, the separation among anionic sites became more regular than that at stage 14. In this study we found some stage specific morphological events in the epithelial-mesenchymal interface in the stomodeal side of the mandibular process at stages preceding the initiation of epithelial organogenesis. PMID- 4038007 TI - [Histamine analogs. 27. Bis(2,2'-histamine)]. PMID- 4038008 TI - Chemical properties-dissolution relationship of non-steroidal antiinflammatory acidic drugs, I. Release of naproxen from inert matrices. PMID- 4038009 TI - [A new amantadine analog]. PMID- 4038010 TI - [Synthesis of flavones cytotoxic against L1210 cells]. PMID- 4038011 TI - [Determination of the protein binding of drugs with continuous ultrafiltration. 7. Protein binding of phenylbutazone]. PMID- 4038012 TI - Clinical and radiological long-term results after primary knee ligament surgery. AB - A total of 77 patients were reviewed 2 to 7 years (average 40 months) after primary operative treatment of an acute knee ligament injury. Fifty percent of the injuries occurred during sports events, the other causes were traffic in 29% of cases and accidents at work, home etc. in 21% of the cases. Cross-country skiing was the cause in half of the sports accidents. There were two annual peaks in the distribution of the injuries: January-March (40% of the cases) and August October (29%). The total number of operations increased steeply during our observation period; 57% of the operations were performed from 1980 to 1981. The most common types of injury were a combination rupture of the anterior cruciate and the medial collateral ligaments (36% of the cases) and a medial collateral ligament rupture alone (31%). According to the follow-up study, excellent or good results were obtained in 59% of the cases and fair or poor in 41%. The pathological clinical and radiological changes after knee ligament injury accumulated markedly under some specific findings. Characteristic of the patients with excellent healing results was that they were younger, received isolated ligament injury and played a great amount of sport, and of the patients with fair or poor results that they were older, received combined ligament injury, suffered quadriceps muscle atrophy and had diminished sporting activity. PMID- 4038013 TI - A method for toxicological evaluation of biomaterials based on colony formation of V79 cells. AB - This report describes a method for cytotoxicity screening of biomaterials based on colony formation of V79 cells. For this test, two metals (titanium and nickel), two ceramics (alumina ceramic and tricalcium phosphate), and two types of polymeric material [high density polyethylene (HDP) and polyvinylchloride (PVC)] were used. Each metal and ceramic was cast into a disk and semidisk 49 mm in diameter and 1 to 2 mm thick. The HDP was molded into a petri dish and PVC was used as a thin film. The materials were sterilized by heating or with ethylene oxide and placed in plastic petri dishes, after which 8 ml cell suspension containing 100 cells were added to each dish. After 1 week, the colonies formed on the materials were fixed, stained, and then the number of colonies was counted. Titanium, alumina ceramic, and HDP showed no differences from the controls in terms of colonies. On the disks and the semidisks of nickel and tricalcium phosphate and on the thin disks of PVC, however, no colonies were detected. The V79 cells used in this experiment showed a rapid and logarithmically stable growth curve and such a high rate of colony formation as to form visible noticeable colonies, and were therefore suitable cells for screening test the cytotoxicity of biomaterials. Unlike other previously reported methods of in vitro cytotoxicity testing, this method permits assay of colonies formed from a single cell after proliferation directly on the materials. Moreover, the test with semidisks permits simple screening to assess the cytotoxicity is caused by either the chemical substances or the physical properties of the materials.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4038014 TI - Fracture of the tibial tuberosity in adolescents. AB - Fracture of the tibial tuberosity is an uncommon injury and rarely occurs after closure of the proximal tibial epiphysis. Three cases of tibial tuberosity fracture over a period of 11 years were treated by open reduction, internal fixation, and immobilization for 6 weeks in plaster of Paris (1970-1980). The postoperative follow-up times were 5, 6, and 7 years. No subsequent deformities were detected. Two patients had secondary posttraumatic patella infera without any symptoms. All patients returned to normal activity. The results demonstrated that this injury in the adolescent knee heals without deformity of functional loss when adequate reduction and fixation of the fracture fragments have been achieved. PMID- 4038016 TI - Long-term results of wear of plastic hip prostheses. AB - The Oscobal-Daubenspeck hip prosthesis was used in 19 hemiarthroplasties and 38 total hip arthroplasties in 1973-1975 and the 10-year experience is presented. Pain recurred some years after the operation. The reason was wear of the high density polyethylene prosthesis head, most pronounced in the hemiarthroplasties, resulting in wear-debris synovitis, resorption of bone, and mechanical loosening of the prosthesis. This design of prosthesis should not be used. PMID- 4038015 TI - Late results in supracondylar humeral fractures in children. AB - The end results of supracondylar humeral fractures in 151 children after an average follow-up period of 15 years are presented. The relationship between the carrying angle and the functional result was analyzed. A deformity of the carrying angle was not felt by the patients to be a cosmetic handicap, and the functional results were not problematic. However, the least satisfactory subjective results in the series were associated with a decrease of the carrying angle by at least 10 degrees and with a significant proportion of the limitations of movement of the elbow joint. PMID- 4038017 TI - Surgical treatment of fractures of the proximal end of the radius in childhood. AB - In childhood, fracture of the neck of the radius is rather common. Generally the fracture is localized in the metaphysis, sometimes with involvement of the epiphysis. Marginal sector fractures, which are common in adults, are very rare. Different types of fractures, indications for surgical treatment, therapeutic procedures, and results are discussed. PMID- 4038018 TI - Ventralization of the tibial tubercle for patellar pain. AB - In this study patellar pain in 37 knees was treated by ventralization of the tibial tubercle. No primary arthrotomy was performed. Seventy-three percent of the knees improved in the opinions of the patients, 11% remained unchanged, and 16% grew worse. Extension did not deteriorate in any knee. No serious complications were encountered. Seven patients had to undergo reoperation. It is suggested that patellar pain should be subdivided into that due to excess pressure, that due to instability, and that due to excess intraosseous venous pressure, in order to find a treatment appropriate to the cause in each case. PMID- 4038019 TI - The posterior cruciate ligament and rotatory knee instability. An experimental study. AB - The importance of the posterior cruciate ligament in relation to valgus-varus and axial rotatory stability in the knee joint was investigated. Mobility patterns were drawn from 20 osteoligamentous preparations after successive transection of the posterior cruciate ligament (PCL), the medial and lateral collateral ligaments, and the posterior joint capsule. The knee joint remained grossly stable after isolated transection of the PCL, and further cutting of either one of the collateral ligaments or of the posterior capsule yielded no greater instability than one should expect from isolated cutting of each of these structures. The posterior cruciate ligament was the stabilizing factor in flexion and external rotation after injury to the lateral collateral ligament and the posterolateral capsule, and it restricted internal rotation after cutting of the medial cruciate ligament and the posteromedial capsule. Valgus instability was markedly increased during the whole range of movement when PCL was included in injury to the medial compartment ligaments, and when included in a lateral compartment injury a further varus instability was found, though only in the flexed or semiflexed knee. No hyperextension could be demonstrated after these injuries. PMID- 4038020 TI - Tibial plateau strength patterns in experimental modular knee replacement. AB - Nondestructive low-strain-rate compression tests were carried out on 12 human cadaver tibiae fitted with a metal modular resurfacing component on the medial or lateral condyle. The tests were done at 20 regularly spaced points on each plateau. The reproducibility of measurement was +/- 16% (95% tolerance limits). A statistically significant correlation was demonstrated between stiffness and ultimate force values obtained from the same points (r = 0.75, P less than 0.005). On the medial plateau the compressive stiffness of the system was maximal when load was applied to the center of the prosthesis, but declined sharply toward the medial and posterior margins. On the lateral plateau maximal stiffness values were obtained more posteriorly, and the stiffness gradients toward the periphery were less marked. Details of surgical technique and specific loading situations that may cause undesirable combinations of load and point of prosthetic component contact are discussed. PMID- 4038021 TI - Residual deformities related to arthrotic change after Perthes' disease. A long term follow-up of fifty-one cases. AB - In order to clarify the long-term results of Perthes' disease and to elucidate the residual deformities, including those of the acetabulum, related to coxarthrosis, 51 patients who had had Perthes' disease were studied clinically and radiologically. Altogether there were 56 affected hips and radiographs taken from onset of disease to maturity were available in all cases. They were followed up for an average of 18 years. Thirteen hips (23%) revealed coxarthrosis. Head deformity, steepness of the lateral edge of the acetabulum, and insufficient acetabular coverage of the femoral head were noted in them both in adulthood and in the active phase of disease. Among these deformities, steepness of the lateral edge of the acetabulum was found to be the most significant prognostic factor and led to coxarthrosis of the affected hip even in the younger adult. Acetabular roof angle, which is a newly designed radiographic measurement, is a good indicator of the prognosis in Perthes' disease. PMID- 4038022 TI - Orthodromic vs antidromic sensory nerve latencies in healthy persons. AB - Sensory nerve action potentials may be evoked antidromically (AD) by stimulating a nerve proximally and recording distally, or orthodromically (OD) by stimulating distally and recording over the nerve trunk proximally. The objective of this study was to compare OD and AD distal latencies in healthy subjects. Fifty-two volunteers (average age 30 years) were tested. Orthodromic and AD sensory distal latencies of the median and ulnar nerves of the nondominant hand were obtained. Hand temperature was controlled at 32C. Six subjects were also tested at a hand temperature of 24C. In all subjects tested the OD latency was shorter than the AD latency. Median nerve AD = 3.14 +/- 0.20 (mean latency in ms +/- 1 standard deviation); median nerve OD = 2.94 +/- 0.20; ulnar nerve AD = 3.07 +/- 0.22; ulnar nerve OD = 2.85 +/- 0.19. Mean difference between the latencies obtained (OD vs AD) for the median and ulnar nerves was statistically significant (p less than 0.001). In addition, this difference was over twice as great at 24C compared to 32C for both median and ulnar nerves. Because of the difference between OD and AD sensory latencies, the standard values obtained using one method cannot be rigorously applied when utilizing the other method. Individual laboratories should develop their own normal values for both OD and AD methods, or be specific in performance of the studies when utilizing standards from the literature. PMID- 4038023 TI - Medial and lateral antebrachial cutaneous nerves: standardization of technique, reliability and age effect on healthy subjects. AB - Techniques for performing antidromic conduction velocity studies on forearm sensory nerves were evaluated in 157 healthy subjects from 17 to 80 years of age. The lateral antebrachial cutaneous nerve (LABCN) and the medial antebrachial cutaneous nerve (MABCN) were studied in the same upper extremity at a distance of 14 cm. The mean values for LABCN were amplitude 18.9 microV, latency to peak 2.8 ms and conduction velocity (CV) 61.5 m/s; for MABCN, amplitude 11.4 microV, latency to peak 2.7 ms and CV 62.7 m/s; and for median nerve, CV 62.3 m/s. SNAPs were obtained in 98% of subjects for each forearm sensory nerve. Age-related changes in the MABCN and LABCN were small, but included a decreased number of high value SNAP amplitudes and CVs with advancing age, whereas values for the median nerve showed a slight overall decrease with age. Sex effects were negligible. It is concluded that: LABCN and MABCN conduction studies can be performed with equal and high reliability using standard techniques and the same constant distance; The amplitude of the LABCN tends to be larger than that of the MABCN (76% of subjects); In some subjects MABCN studies are technically more difficult to perform than LABCN studies; Forearm sensory nerve studies may be used in addition to median nerve sensory studies in the evaluation of peripheral neuropathy, brachial plexopathy and local neuropathic conditions. PMID- 4038024 TI - Sensory palmar stimulation in the diagnosis of carpal tunnel syndrome. AB - The measurement of motor and sensory latencies of the median and ulnar nerves using conventional techniques in able-bodied subjects and patients with a history compatible with carpal tunnel syndrome (CTS) is described. The results obtained by conventional techniques are compared with measurement of median nerve sensory latency obtained by palmar stimulation and the difference of median-ulnar nerve distal sensory latencies. It is concluded that the use of measurement of median palmar sensory latency under the flexor retinaculum adds to the sensitivity of the nerve conduction studies in the diagnosis of CTS. It is suggested that, in patients with suspected CTS in whom conventional nerve conduction studies are normal, other techniques such as the measurement of palmar sensory latency, difference between median and ulnar nerve distal sensory latency and examination of all the digits should be carried out. PMID- 4038025 TI - Changes in motor unit action potential parameters in monopolar recordings related to filter settings of the EMG amplifier. AB - We studied the effect of different electromyographic amplifier settings on various parameters of motor unit potentials (MUPs) as recorded by the monopolar needle. Of the four filter settings used--2Hz-10kHz, 20Hz-10kHz, 20Hz-2kHz and 500Hz-10kHz--2Hz-10kHz yielded longest duration recordings. Reductions of all parameters of the MUP except for phases and turns were demonstrated with the 500Hz-10kHz filter. No significant differences were noted between recordings obtained with 20Hz-10kHz and 20Hz-2kHz filters. Frequencies below 500Hz were more significant in determining the various parameters of the MUP than were those above 2kHz. Most suitable filter settings for recording MUPs were 2Hz-10kHz and 20Hz-10kHz. Measurements of MUPs were shown to be specific for a given filter setting. PMID- 4038026 TI - Physical activity: its influence on nerve conduction velocity. AB - In a group of 40 healthy subjects, distal and proximal latencies of the median, tibial, and peroneal motor, and sural sensory nerves and their respective skin surface temperatures (Tsk) were measured before and after walking or bicycling. The baseline tests were performed 30 minutes after resting in a constant room temperature of 24C. The ambulation or bicycling task was continued for 30 minutes at a constant rate. Postactivity tests were performed within 30 minutes and between 45 to 60 minutes after termination of activity. Another test was done 75 to 90 minutes after bicycle exercise. After walking, there was a significant increase in Tsk in all lower extremity nerves tested (p less than 0.01). The increases were accompanied by faster distal and proximal latencies in both testing periods (p less than 0.01). Median nerve Tsk, distal and proximal latencies did not differ significantly from baseline values initially, but 45 minutes after walking Tsk was elevated and proximal latency had become faster (p less than 0.01). Following bicycling, lower extremity Tsk was significantly reduced over tibial, peroneal, and sural nerves by the third testing period (p less than 0.01) but only sural latencies were significantly prolonged (p less than 0.05) by this time. In the upper extremities median Tsk was significantly elevated and distal latency had become significantly faster 45 minutes after bicycling. Our data suggest that activity significantly influences nerve conduction latency results due to tissue temperature alteration. In addition, 30 minutes of rest after activity may not be sufficient time for the lower extremity temperatures to become stable. PMID- 4038027 TI - Electromyographic kinesiology of lower extremity muscles during slope walking. AB - To investigate the phasic activity of the lower extremity muscles during up- and downslope walking, five muscles of ten healthy men were examined by telemetered electromyography (EMG). The muscles were the tibialis anterior (TA), gastrocnemius (Gc), rectus femoris (RF), semitendinosus (St) and gluteus maximus (GM). The inclination of the slope was 3, 6, 9 and 12 degrees. EMG of the muscles and the time factors of a walking cycle were recorded by a 12-channel polygraph simultaneously. In upslope walking, the duration of TA, St and GM activity was longer and that of RF activity was shorter than in level walking. The phasic pattern of Gc in upslope walking was the same as in level walking. In downslope, the duration of Gc and RF activity was longer than on the level. St showed biphasic activities. The phasic pattern of TA and GM was nearly the same as in level walking. The phasic activity of the muscles altered with an inclination over 6 degrees in upslope, and over 3 degrees in downslope. The findings indicate that the muscles stabilize the knee and ankle joint much more in slope walking than in level walking, and in slope walking they also exert themselves to elevate or lower the body weight. PMID- 4038028 TI - Cerebral palsy: postural-locomotor prognosis in spastic diplegia. AB - Prognosis of locomotion in children with cerebral palsy (CP) is complicated by the variety of motor and other neurologic deficits in each case. Children presenting with spastic diplegic (SD) CP related to prematurity generally demonstrate more uniform and comparable neuromotor abnormalities. In this study, longitudinal data were collected on the early postural-locomotor development of children with spastic diplegic cerebral palsy (SDCP). The data were then correlated with the level of ambulatory function attained. Fifty spastic pediatric patients, aged 5 to 19 years, were included in the study completed in 1982. The duration of follow-up ranged from 4 to 16 years. The study is based upon a method of assessing preambulatory milestones, a classification of ambulatory function into four levels of ability, and correlates these two sets of data. The results indicate that the motor control of sitting and crawling at 1 1/2 to 2 1/2 years was predictive of the eventual level of ambulatory function the child was able to attain and maintain. PMID- 4038029 TI - Hip flexion contractures: a comparison of measurement methods. AB - Rater reliability characteristics of four positioning techniques used to measure hip extension (prone hip extension, Thomas, Mundale, and pelvifemoral angle) were compared. Two raters examined 45 children (90 hips), including patients with spastic diplegia and with meningomyelocele, who are prone to developing hip flexion contractures, and healthy subjects. Retests were performed on 21 children. The least reliable readings in the cerebral palsy group were found from tests using the Thomas technique, and in the meningomyelocele group using the Mundale technique. The pelvifemoral angle is more time consuming, and no more accurate than other methods. Considering the ease of measurement, reliability and reproducibility, we recommend use of the prone hip extension test for patients with cerebral palsy and for those with meningomyelocele, and recommend the Thomas test as an alternative for nonspastic patients. PMID- 4038030 TI - Reality orientation for brain injured patients: group treatment and monitoring of recovery. AB - A reality orientation group for brain injured patients was developed to improve attention deficits, confusion and anterograde amnesia during post-traumatic amnesia (PTA). Seven behavioral objectives are used to define adequate orientation, attention, immediate retention, episodic recall and use of memory aids. Daily performance in each of these areas is aggregated to establish a weekly summary score. Inter-rater reliability was found to be 0.875. The weekly aggregate score assesses recovery during PTA with increases corresponding to qualitative changes in patient progress. This weekly score has proven valuable as a management tool in rehabilitation by indicating when advanced training is warranted, whether a plateau in progress has been reached and when deterioration may be occurring. PMID- 4038031 TI - Rehabilitative rheumatology content in current rehabilitation medicine training programs. AB - The Council on Rehabilitative Rheumatology of the American Rheumatism Association, through the Education Subcommittee, surveyed directors of 69 approved rehabilitation medicine residency training programs to assess the nature of training in rehabilitative-rheumatology and whether the directors believed this training to be adequate. Sixty-one directors responded, with 84% of the respondents reporting a rheumatology department in their hospitals and 43% reporting a formal rotation for their residents in rheumatology. Fifty-nine (97%) reported their residents received lectures in rheumatology. Fifty-five (90%) reported lectures given by a physiatrist in the rehabilitative management of rheumatic diseases. Only 21 (34%) reported a physiatrist-attended rheumatology outpatient clinic. Fifty-one (82%) desired a closer liaison with the rheumatology department. Thirty-seven (61%) indicated their residents received adequate training on the diagnosis of rheumatic diseases, and 46 (75%) adequate training in rehabilitative management, while 59 (97%) desired a concise handbook which emphasizes the rehabilitative management of rheumatic diseases. A previous survey of 100 arthritis fellowship programs approved by the American Medical Association brought 81 responses, of which only 43% considered that their Fellows had adequate training in rehabilitative rheumatology. Physiatrists attended clinics 21% of the time and patient care rounds 19%. Ninety-four percent desired a syllabus. Both surveys indicated limited interaction between the two specialties and leads us to conclude that a rehabilitative-rheumatology handbook would be desirable, closer liaison of rehabilitation faculty with rheumatology faculty is needed to respond to individual training needs, more active participation by a physiatrist in patient care conferences may be necessary for adequate education in rehabilitative-rheumatology. PMID- 4038032 TI - Cheiralgia paresthetica and linear atrophy as a complication of local steroid injection. AB - Cheiralgia paresthetica, a mononeuropathy of the superficial branch of the radial nerve, is an uncommon problem, usually resulting from local trauma to the wrist. This report describes a 27-year-old patient who developed subdermal atrophy following local hydrocortisone injection as a treatment for deQuervain's tenosynovitis. Subsequently, she developed linear skin atrophy, a rare complication of steroid injection thought to result from lymphatic spread of the steroid suspension, extending proximally from the initial atrophic area in her hand into her forearm. Soon after wearing a wristwatch on the affected wrist, she developed symptoms of cheiralgia paresthetica. Linear atrophy was found to traverse the superficial radial nerve and was considered to contribute to the symptoms. It is important to be aware that subcutaneous atrophy may follow the lymphatics with injections of steroid. PMID- 4038033 TI - Calcitonin therapy in prolonged immobilization hypercalcemia. AB - During the course of hospitalization for comprehensive rehabilitation, an 11-year old boy with a C4-C5 spinal cord injury developed hypercalcemia which persisted for 131 days. The total serum calcium was closely monitored during six treatment periods during which calcitonin was administered. The response to calcitonin was variable and limited by the occurrence of the escape phenomenon. Glucocorticoids were also partly effective but other antihypercalcemic therapies including low calcium diet, diuretics, IV saline, wheelchair sitting, and oral phosphates were not. A review of the pathophysiology of immobilization hypercalcemia indicates that increased bone resorption is primarily responsible for the disorder. Both calcitonin and glucocorticoids are potent inhibitors of bone resorption, and glucocorticoids can prevent escape from calcitonin's calcium-lowering effect. We suggest that combination therapy with calcitonin and glucocorticoids be utilized in severe hypercalcemia in order to take advantage of the rapid effect of calcitonin and the more sustained effect of glucocorticoids. PMID- 4038034 TI - Autonomic dysreflexia due to medication: misadventure in the use of an isometheptene combination to treat migraine. AB - Autonomic dysreflexia, a syndrome sometimes occurring in spinal cord injured (SCI) individuals, may be life-threatening. It involves, in varying degrees, hypertension, diaphoresis, headache, bradycardia, anxiety, and flushing and is believed due to unrestricted sympathetic activity below the level of the lesion in individuals with injuries above T4-6. The most frequent causes of the syndrome are urinary infections, rectal impaction, bladder distention, and decubitus ulcers. To our knowledge, medication has seldom been described as causal agent. We report here on an autonomic dysreflexic syndrome following use of an isometheptene combination (Midrin), to treat migraine. The individual involved is a C4-quadriplegic man with a long history of migraines. He was given a standard initial adult dose of the medication. Over a one-hour period, he was initially relieved of the headache, but then noted a new more severe headache, diaphoresis, and flushing. His vital signs showed progressive BP elevation to 210/130 and a relative bradycardia. Treatment over the next three hours was limited to elevation of the head of the bed and observation, during which his vital signs returned to baseline and he became asymptomatic. This experience reinforces the belief that sympathomimetic drugs in general, and isometheptene in particular, should be used in caution in patients with high-level SCI. PMID- 4038035 TI - PULSES profile in retrospect. PMID- 4038037 TI - Properties of attitude response systems in analytic-dynamic motivation research. PMID- 4038036 TI - Judged seriousness of crimes and offenses: 1927, 1967, and 1984. PMID- 4038038 TI - [Semantic dimensions of positive and negative affect concepts]. PMID- 4038039 TI - [Emotional content, imagery, concreteness and meaningfulness of 580 adjectives: contribution to the standardization and evaluation of relation hypotheses]. PMID- 4038040 TI - [Discrete probabalistic reaction models as categorial regression models]. PMID- 4038041 TI - [Experimental study of simultaneous translating: unit formation and time coordination]. PMID- 4038042 TI - [Proposition related changes in word meaning as differential priming]. PMID- 4038043 TI - [Revision of predicate-centered sentence theories]. PMID- 4038044 TI - [Limits of marker theoretical concepts]. PMID- 4038045 TI - [Speech intelligibility as dependent on prosody]. PMID- 4038046 TI - Yersinia enterocolitica infections in children. PMID- 4038047 TI - The mathematical analysis of the data concerning the rheumatic fever diagnostic criteria. PMID- 4038048 TI - Streptolysin "0" a potentially useful antigen for complement-fixing reactions. PMID- 4038049 TI - Anti-neuraminidase antibody response after administration of a split influenza vaccine. PMID- 4038050 TI - Ultrastructural aspects of Blastocystis hominis strain resistant to antiprotozoal drugs. PMID- 4038051 TI - Vibrio vulnificus in sea water: a possible cause of acute diarrhea in man? PMID- 4038052 TI - Multiple-organ failure. Generalized autodestructive inflammation? AB - As multiple-organ failure (MOF) has been generally associated with sepsis, the importance of bacterial sepsis was evaluated retrospectively in 55 trauma and 37 intra-abdominal-sepsis patients with MOF. The severity of MOF was graded, and an analysis was made of day of onset, incidence, severity, sequence, and mortality of organ failures. No difference was found between groups in sequence, severity, or mortality of organ failures. In contrast, bacterial sepsis was found in 65% of intra-abdominal-sepsis patients but only in 33% of trauma patients. It is concluded that sepsis is probably not the essential cause of MOF. Instead, an alternative hypothesis is presented involving massive activation of inflammatory mediators by severe tissue trauma or intra-abdominal sepsis, resulting in systemic damage to vascular endothelia, permeability edema, and impaired oxygen availability to the mitochondria despite adequate arterial oxygen transport. PMID- 4038053 TI - Sequential pneumatic compression for lymphedema. A controlled trial. AB - We examined prospectively the effect of a new compression device for lymphedema, which utilizes a short duration and high-pressure cycle, that provides a sequential milking pattern to the limb through multiple compartments. Twenty-five patients (seven patients for upper-extremity and 18 for lower-extremity problems) underwent 24 hours of treatment. All extremities showed a decrease in circumferential measurements with the maximal reduction occurring at the wrist (45%) for the upper extremities and at the mid-calf (47%) for the lower extremities. Lower-extremity leg volume was reduced by 45%. Despite the high pressures no elevation in serum muscle enzyme levels was noted. This device reduced lymphedematous limbs rapidly and safely. PMID- 4038054 TI - Peripheral vascular trauma from close-range shotgun injuries. AB - This report summarizes an eight-year experience (1976 to 1983) with 49 close range shotgun blasts with associated major vascular injuries seen in a large urban hospital. Injuries to the upper extremity (40%), lower extremity (56%), and neck (4%) were seen. A high frequency of associated deep venous injury (82%), nerve injury (37%), fracture (33%), massive soft-tissue loss (43%), and compartmental hypertension (39%) was observed. There were no deaths in this series, and the limb salvage rate was 96%. Neither patient with multiple carotid artery injuries suffered a neurologic deficit. We attribute our success in the management of these complex injuries to rapid fracture immobilization, early and aggressive use of fasciotomy, adequate debridement of devitalized tissue, repair of deep venous injuries, arterial repair with autogenous tissue, and extra anatomic bypass grafting in selected cases. PMID- 4038055 TI - Aneurysms of the abdominal aorta. Incidence in blacks and whites in North Carolina. AB - We examined race and sex relative to the unexpected finding of an abdominal aortic aneurysm (AAA) at 1,665 autopsies plus 545 abdominal computed tomographic scans in subjects over the age of 50 years. We compared our demographic data with those of North Carolina and our hospital to determine if the data base was representative. White males had a higher incidence (4.2%) of AAA than any other group of race and sex (1.2% to 1.6%) or combination of groups. Although whites (2.9%) had a higher incidence than blacks (1.5%) and males (3.4%) had a higher incidence than females (1.3%), this can be attributed to the influence of the white male. The demographic data of the group studied were similar to those of our institution's admissions and to the North Carolina population. We conclude that (1) there is an increased incidence of AAA in the white male compared with the white female, black male, and black female in North Carolina; (2) there is no difference in the incidence of AAA in the white female, black male, and black female; (3) race alone may not influence the incidence of AAA as there was no difference between white and black females. PMID- 4038056 TI - Pentoxifylline in the treatment of experimental peritonitis in rats. AB - The objective of this study was to determine the effect of pentoxifylline on the clinical and pathologic course of experimentally induced peritonitis in rats. This drug is a methyxanthine derivative that has vasodilating properties and may decrease platelet aggregation. Peritonitis was induced in 40 Wistar rats by creating a closed ileal loop 4 cm long 5 cm from the ileocecal valve. The animals were divided into two groups of 20 animals each. The first group served as controls, while each animal of the second group received 17 mg/kg/day of pentoxifylline intramuscularly from the day of operation until 30 days postoperatively. The survival rate was significantly increased in the group receiving pentoxifylline and adhesion or abscess formation was considerably reduced. We concluded that the administration of pentoxifylline prolongs significantly the survival of animals with experimental peritonitis and reduces the development of adhesions and abscesses in the peritoneal cavity. This beneficial effect may be attributed to decreased fibrinogen deposits and increased fibrinolytic activity within the peritoneal cavity, thus rendering the bacteria more susceptible to cellular and noncellular clearing mechanisms. PMID- 4038057 TI - Early local complications from intestinal stomas. AB - A retrospective review of 610 consecutive patients with intestinal stomas constructed at Cook County Hospital, Chicago, was carried out to analyze early local complications with respect to stoma type and to compare complication rates by surgical specialty. A total of 197 complications were recognized in 158 patients for a corrected complication rate of 25.9%. Peristomal skin irritation (42.1%) was the most frequently recognized early complication in this study. Ileostomy was associated with the highest morbidity (40%) of any type of stoma. Emergency stoma formation seems to be associated with the highest complication rates, probably because of suboptimal stoma placement. The morbidity of stoma formation seems to be related to the amount of formal training in gastrointestinal tract surgery. Technical guidelines for stoma construction are presented to help minimize these complications. PMID- 4038058 TI - Late relapse from cutaneous stage I malignant melanoma. AB - In 1,283 patients with cutaneous stage I malignant melanoma who had ten or more years of follow-up, the incidence of late recurrence (first evidence of metastases occurring ten or more years after melanoma diagnosis) was 2.7%. None of the factors of prognostic importance (anatomic site, tumor thickness, ulcerative state of primary lesion, or initial surgical treatment) proved useful in predicting those patients with late recurrence. There was no sex or age difference in either incidence of late recurrence or prognosis subsequent to recurrence. Prognosis subsequent to late recurrence depended on the site of the recurrence. Survival after distant metastases became evident was extremely short. However, in the majority (53%) of patients, late recurrence was local and survival subsequent to treatment of these metastases was often protracted, emphasizing the importance of long-term follow-up in all patients with cutaneous melanoma. PMID- 4038059 TI - Can general surgery improve the outcome of the head-injury victim in rural America? A review of the experience in American Samoa. AB - We analyzed the records of 50 head-injury patients managed by general surgeons from 1974 to 1981 in American Samoa. Patients were divided into three groups. Group 1 was awake and alert (n = 24). Group 2 was obtunded by talking (n = 7). Group 3 was comatose (n = 20). All patients were managed with diagnostic burr hole procedures. Eighteen of the 20 unconscious patients had an intracranial hematoma. Five of the seven obtunded patients had an intracranial hematoma. Three of the nine deaths were directly attributable to a delay in diagnosis of an intracranial hematoma. We conclude that a burr-hole procedure in unconscious head injury patients in rural hospitals is a safe and effective method of diagnosing and treating extradural and subdural hematomas. General surgery residents should receive training in operative head-injury management, to improve the care of the head-injury victim in rural America. PMID- 4038060 TI - Epiploic disorders. Conditions of the epiploic appendages. AB - Disorders of the epiploic appendages are rarely diagnosed preoperatively and usually result from torsion with subsequent infarction. No diagnostic test or clinical symptoms are pathognomonic of this process, which is a disease of middle age and rarely life-threatening, and the most common preoperative diagnosis is acute appendicitis. An analysis of case information reported in the surgical literature has been combined with our recent experience involving ten cases. Fifty-eight percent of the patients in this collected series were male, and the average age in both sexes was 42 years. The sigmoid colon was the most frequent site of these disorders (41.5%), and acute appendicitis was the most common preoperative diagnosis (37.7%). The treatment is ligation, excision, and occasionally seromuscular inversion. When encountered at exploration, this entity may represent the sole etiology of the abdominal pain if exploration is otherwise negative. PMID- 4038061 TI - Popliteal vein aneurysm causing pulmonary embolus. AB - A case of pulmonary embolus arising from a popliteal vein aneurysm is reviewed. These aneurysms are believed to be developmental in origin; with the exception of embolic phenomenon, these venous anomalies are generally asymptomatic. To our knowledge, only six cases have been previously reported. Physical examination was not helpful, and noninvasive studies were of no value in detecting the aneurysm. Venography was the only reliable diagnostic test. Because popliteal vein aneurysms are a potential source of emboli, surgical intervention is recommended. Venous aneurysmorrhaphy or excision of the aneurysm with a venous bypass are the surgical procedures most often carried out. Aneurysmorrhaphy appears to be associated with an unacceptably high rate of thrombosis; excision with placement of a vein graft may be a more satisfactory alternative. PMID- 4038062 TI - Squamous cell carcinoma of the cecum. AB - Squamous cell carcinoma of the cecum above the peritoneal reflection has rarely been reported. The pathogenesis of squamous cell carcinoma of the cecum is speculative. A report of two cases and a review of the literature were undertaken to study the significant pathologic causative mechanism of this disease. A significant causative factor is trauma to the cecal wall followed by chronic irritation. The clinician should be alerted to the fact that operative trauma to the colon followed by chronic irritation or prolonged chronic infection may be one causative factor in squamous cell carcinoma of the colon. PMID- 4038063 TI - Three synchronous multiorgan primary cancers. All stage I. AB - A patient who has three separate, synchronous, early (stage I) primary cancers of the right lung, right breast, and stomach and whose disease is simultaneously diagnosed and successfully treated sequentially within a single hospital admission is unique. While multiple primary malignant neoplasms are not uncommon, to our knowledge, there has been no report of triple stage I synchronous carcinomas in separate major organ systems. Age, immunodeficiency, somatotype, hereditary tendencies, hormonal and environmental factors, and previous therapy have been incriminated as etiologic factors. Accurate tissue diagnosis and tumor staging are mandatory. In patients with diagnosed cancer, pulmonary lesions should never be presumed metastatic. Individual tumors should be treated independently of other concomitant lesions, and each treatment approach should be curative in nature. Patients with proven multiple malignant neoplasms carry a higher risk of developing other primary neoplasms. PMID- 4038064 TI - Brachial plexus injuries with causalgia resulting from transaxillary rib resection. AB - In each of four patients with suspected thoracic outlet syndromes, the transaxillary approach to resection of the first thoracic and cervical ribs resulted in severe and permanent damage to the brachial plexus. The most severe sequela was causalgia. Weakness of the hand muscles, sensory deficits, and autonomic dysfunction also occurred. Abuse of narcotic analgesics was common. Two patients suffered severe psychological depressions, with one committing suicide. Current enthusiasm with transaxillary rib resections in cases of thoracic outlet syndrome should be tempered by the possibility of severe and permanent injury to the brachial plexus and intractable causalgia. PMID- 4038065 TI - Bile duct varices. AB - The diagnosis of biliary duct varices and portal vein occlusion should be considered when nodular or notched defects in the wall of the biliary duct system are shown by cholangiography or when pedunculated vascular structures in the bile ducts are seen at surgery. We present two cases of common hepatic and common bile duct varices due to portal vein occlusion. PMID- 4038066 TI - Ultrasonic fragmentation. A new technique for mucosal proctectomy. AB - We report a new technique for mucosal proctectomy that does not require manual separation of the mucosa and submucosa from the underlying muscularis. Mucosal proctectomy using ultrasonic fragmentation of the rectal mucosa was performed in four patients. Three had severe ulcerative colitis, and one patient had radiation proctitis with a rectal stricture. In all cases an endorectal pullthrough with anastomosis to the area of the dentate line was performed. Healing after ultrasonic mucosal proctectomy occurred without infection or retraction. Ultrasonic fragmentation offers an alternative to the standard technique of mucosal proctectomy. This new method is useful in those patients in whom separation of the rectal mucosal layer is difficult to perform. PMID- 4038067 TI - The effect of the amount of urea in the diet on the contents of amino acids and other components of duodenal digesta in young bulls. AB - Young bulls of average live weight 130 kg, with rumen cannulae and re-entrant cannulae of the proximal duodenum, were fed on a diet of maize meal from whole plants, potato starch and a mineral mixture, containing 7.6% crude protein in DM (group IV). For three groups the diet was supplemented to contain about 17.5% crude protein with groundnut oilmeal (group I), grundnut oilmeal and urea, 27 and 31.2% of dietary N (group II) or urea alone (group III). The content of gross energy was similar in all diets. The amount of total N entering the duodenum in groups I to IV was 61.6, 59.2, 49.9 and 38.0 g/day and apparent digestibility of N in the stomachs was -0.4, 5.8, 21.6 and -44.4%. Total amount of amino acids in the duodenal digesta was, in the same order, 257, 261, 215 and 170 g/day, equivalent to 80, 116, 165 and 127% of intake. The ratio of the amounts of essential to nonessential amino acids was in feed 0.84 and in duodenal digesta in all groups 0.98. The amount of lysine in duodenal digesta was 1.5, 2.0, 3.5 and 2.5 times its intake in the same order of the groups. PMID- 4038068 TI - Oligonucleotide fingerprints of antigenically related bovine coronavirus and human coronavirus OC43. AB - Virion RNAs from the bovine enteric coronavirus and the human respiratory coronavirus OC43 were compared by one dimensional gel electrophoresis and by oligonucleotide fingerprinting. For each virus, approximately 55 per cent of the RNA migrated as a 6.8 Md species, 10 per cent as a 0.68 Md species, and 15 per cent as heterogeneous small molecular weight RNA. A sequence homology of greater than 96 per cent was observed between the 6.8 Md species from the two viruses. The 0.68 Md RNA is apparently an intravirion, subgenomic, polyadenylated molecule based on RNAse studies, oligo (dT)-cellulose chromatography, and hybridization to a cDNA clone of the 3' terminal 1.19 Kb region of the bovine coronavirus genome. PMID- 4038069 TI - Rapid focus reduction neutralization test of Japanese encephalitis virus in microtiter system. Brief report. AB - An improved rapid focus reduction neutralization test for Japanese encephalitis (JE) virus in microtiter system was developed. 96-well tissue culture plates were used for preparation of cell monolayers and PAP (peroxidase-antiperoxidase) staining technique was used for visualization of foci of infected cells. As the test has many advantages over other methods, it might be applied widely for rapid diagnosis and seroepidemiological studies. PMID- 4038070 TI - Ultrastructural changes of motoneurons in monkeys infected with enterovirus 71. Brief report. AB - Tissues of the central nervous system (CNS) of cynomolgus monkeys were examined by electron microscopy after intraspinal inoculation of enterovirus 71 (E71). A characteristic finding was the appearance of numerous membrane-bound vesicles (Mbvs) in affected motoneurons. Similar Mbvs were also present in E71-infected cynomolgus monkey kidney (CMK) cells in culture. Virus-like particles were found within or around Mbvs in motoneurons as well as in infected CMK cells in culture. Neither Mbvs nor E71 antigens as detected by immunofluorescence were found in supporting tissues, vascular endothelium, or inflammatory cells. Quite similar findings had been seen in poliovirus infections. It was suggested that the appearance of Mbvs in the cytoplasm of motoneuron is the direct results of virus multiplication in E71 infection as in poliovirus infection. PMID- 4038071 TI - Rubella virus RNA: effect of high multiplicity passage. AB - Evidence for the amplification of defective interfering particles of rubella virus after passage at high multiplicity has been obtained. The process is associated with the production of subgenomic rubella RNA species. PMID- 4038072 TI - The major internal protein, p27, of a retrovirus-like particle participates in immune complex formation in psoriasis. AB - The major internal protein, p27, of a retrovirus-like particle isolated from the urine of a patient with psoriasis has been purified and used in an indirect ELISA to detect human antibodies against the virus antigen. Rabbit anti-p27 antiserum has been applied to detect p27 antigen present in clinical specimens. p27 and anti-p27 antibodies have been demonstrated in extracts from psoriatic scales. Insignificant amounts of free anti-p27 antibodies are present in serum, but both p27 and anti-p27 antibodies have been detected in circulating immune complexes obtained from serum or synovial fluid from patients with psoriatic arthritis. PMID- 4038073 TI - [Significance of lymphocyte blastogenesis in the identification of the specific antigen and the diagnosis of budgerigar fancier's lung]. PMID- 4038074 TI - [The increase in serum IgE and anti-Dermatophagoides pteronyssinus (anti-DP) specific IgE levels during stay at home in institutionalized asthmatic children. The role of house dust mite in the dwelling as a trigger of asthma attack in mite sensitive patients]. PMID- 4038075 TI - [A case of intolerance to aspirin in childhood]. PMID- 4038076 TI - [Relationship between airway hyperreactivity and various atopic factors in bronchial asthma]. PMID- 4038077 TI - [Secretory IgA in saliva of asthmatic children]. PMID- 4038078 TI - [A case of cat-induced asthma]. PMID- 4038079 TI - [Survey of the association of dermatomyositis and pulmonary fibrosis]. PMID- 4038080 TI - [Partial characterization of a human lymphokine that stimulates collagen production by fibroblasts]. PMID- 4038081 TI - [The influence of road dust on asthmatic children]. PMID- 4038082 TI - [Studies of the pollen grains causing pollinosis (10). Correlation between sugi pollinosis and mean ten day temperature in July]. PMID- 4038083 TI - [Administration of E-0686 granule, sustained-release theophylline, for asthmatic infants]. PMID- 4038084 TI - [Changes in nasal resistance induced by nasal provocation in nasal allergy]. PMID- 4038085 TI - [Occupational apple and pear pollinosis among apple- and pear-growing farmers and cross-allergenicity between Japanese apple pollen and Japanese pear pollen]. PMID- 4038086 TI - [Peach (Prunus persica) pollinosis in people who have not been engaged in growing peaches]. PMID- 4038087 TI - [Simple and rapid estimation of serum theophylline concentrations using the apoenzyme reactivation immunoassay system]. PMID- 4038088 TI - [The role of normal flora in bronchial asthma--significance of alpha Streptococcus as an allergen]. PMID- 4038090 TI - Clinical dermatology: an exercise in gross dermatopathology. PMID- 4038089 TI - Property of immunoglobulin binding substance from the granary weevil. PMID- 4038091 TI - Primary biliary cirrhosis and autoimmune disorders: a review. PMID- 4038093 TI - Medicine: the death of a profession. PMID- 4038094 TI - Hypertension in acute ischemic strokes. Treat. PMID- 4038092 TI - Intramuscular myxoma: report of two cases and review of the literature. PMID- 4038095 TI - Hypertension in acute ischemic strokes. PMID- 4038096 TI - Prolonged confusion due to absence status following metrizamide myelography. AB - A case of absence status epilepticus resulted from metrizamide myelography. The acute confusional state following metrizamide myelography is briefly reviewed and compared with the confusional state resulting from adult-onset absence status. The similarities suggest that absence status may in fact be a relatively common cause of prolonged confusion following the use of metrizamide. Given the difficulty in clinical diagnosis and the excellent response to anticonvulsants, the possibility of absence status should be specifically excluded by EEG in any person suffering prolonged confusion following metrizamide myelography. PMID- 4038097 TI - Seizures in an atelencephalic infant. Is the cortex essential for neonatal seizures? AB - Clinical and electrographic seizures were recorded in an infant with atelencephaly. Because the infant had no cerebral hemispheres, the ictal discharges were presumed to arise from the disorganized diencephalic derivatives that occupied the entire supratentorial space. The case provided strong support for the concept that, unlike epileptic seizures in older patients, some types of neonatal seizures may originate and propagate exclusively in subcortical structures. This may explain the striking dissociation between the electrographic and behavioral aspects of seizures occasionally observed in newborns, as well as the frequent intractability of such seizures to standard anticonvulsants. PMID- 4038098 TI - Extramedullary hematopoiesis presenting as transient ischemic attack. PMID- 4038099 TI - Movement disorders and objective measurements. PMID- 4038100 TI - Accuracy of medical terminology. PMID- 4038101 TI - Various consequences of subcortical stroke. Prospective study of 16 consecutive cases. AB - Sixteen consecutive cases of subcortical stroke were studied prospectively and systematically. Behavioral and neurological manifestations of different sides, sites, and causes of lesion were evaluated by means of daily, standard observations during the patient's hospitalization and formal testing at monthly intervals thereafter. Language and cognitive impairments were observed following hemorrhagic and nonhemorrhagic strokes to both the left and right thalami and basal ganglia. The patterns were unlike those characteristic of traditional aphasia syndromes. One patient was asymptomatic; four demonstrated only dysarthria or dysarthria with abnormal affect; and 11 displayed a combination of speech, language, and cognitive deficits. Language skills recovered more rapidly and completely than did cognitive skills. Recovery was most dramatic within the first six to eight weeks after onset. PMID- 4038102 TI - Subcortical arteriosclerotic encephalopathy (Binswanger's disease). Computed tomographic, nuclear magnetic resonance, and clinical correlations. AB - Twenty-three elderly patients were found to have a consistent pattern of leukoencephalopathy by computed tomography and nuclear magnetic resonance imaging. Eight patients presented with vague, nonspecific symptoms and had no neurologic deficits. The other 15 patients had neurologic deficits that presented in one of three ways: stroke, seven patients; slowly progressive dementia and gait disturbance, five patients; or slowly progressive dementia alone, three patients. Risk factors for arteriosclerosis (hypertension, diabetes) were present in 18 patients (78%). The necropsy of one patient revealed arteriosclerotic vasculopathy characteristic of subcortical arteriosclerotic encephalopathy (SAE) or Binswanger's disease. Subcortical arteriosclerotic encephalopathy may be a relatively common affliction of elderly patients, most of whom have risk factors for arteriosclerosis. The modes of presentation and associated clinical signs are variable, and more than one third may have no neurologic deficit. In some cases SAE overlaps with normal pressure hydrocephalus by clinical and neuroimaging criteria. Some patients with normal pressure hydrocephalus who do not respond to ventricular shunting may actually have SAE. PMID- 4038103 TI - Usefulness of heparin in initial management of patients with recent transient ischemic attacks. AB - We evaluated the efficacy of short-term intravenous heparin therapy in 74 patients with recent transient ischemic attacks (TIAs). The patients were treated after hospitalization until operation or long-term medical treatment was instituted. Heparin was given in a continuous infusion to maintain an activated partial thromboplastin time of 1 1/2 to 2 1/2 times control values. During the treatment period, 12 patients (16.2%) had recurrent TIAs and five (6.8%) had cerebral infarction. Bleeding complications occurred in nine patients (12.2%). In this limited series, heparin did not prevent recurrent TIAs or cerebral infarction among high-risk patients with recent TIAs. PMID- 4038104 TI - Magnetic resonance imaging after 'diffuse' nonmissile head injury. A neurobehavioral study. AB - The diagnosis of diffuse brain injury is considered when computed tomography provides no evidence of an intracranial mass lesion in acute nonmissile head injury. Magnetic resonance imaging (MRI) of a young woman who had sustained severe diffuse brain injury five years earlier disclosed multifocal lesions involving the frontal, temporal, parietal, and occipital lobes. We report the results of serial neurobehavioral assessment for clinical correlation with the brain lesions visualized by MRI. Pending confirmation of our findings in a series of patients studied by MRI during the acute and chronic stages of recovery from head injury, we postulate that the presence and type of neurobehavioral sequelae of diffuse brain injury are related to the intrahemispheric loci of predominantly white matter lesions and degeneration. PMID- 4038105 TI - Tubular aggregates. Their association with neuromuscular diseases, including the syndrome of myalgias/cramps. AB - Tubular aggregates of muscle are distinctive structures seen in a wide variety of disorders. We reviewed 1,500 consecutive muscle biopsy specimens for the presence of tubular aggregates. Fifteen biopsy specimens (1.0%) were found with this abnormality. All patients were male, and seven had specific diagnoses based on clinical, biochemical, morphologic, and electrophysiologic criteria: hypokalemic periodic paralysis (two patients); hyperkalemic periodic paralysis (one patient); myotonia congenita (one patient); inflammatory myopathies (three patients). The remaining eight patients had a syndrome characterized predominantly by muscle pain and/or cramps, not necessarily precipitated by exercise. Although tubular aggregates constituted the predominant abnormality on muscle biopsy specimens in these cases, other mild, nonspecific changes were noted. PMID- 4038106 TI - Psychomotor status. AB - Four case histories are reported, including a review of the available literature since 1956 (35 cases). Contrary to what might be inferred from the limited number of published cases, the actual prevalence of psychomotor status must be much higher, as probably many patients' conditions are mistakingly diagnosed as psychiatric. Neurologic and electroencephalographic examinations are indicated in all patients with an apparently acute psychotic behavior combined with an altered state of consciousness. PMID- 4038107 TI - Hypertension in acute ischemic strokes. Not to treat. PMID- 4038108 TI - Identification of proteins in contact lens surface deposits by immunofluorescence microscopy. PMID- 4038109 TI - Removal of subcutaneous dermoids with the assistance of a cryoprobe. PMID- 4038110 TI - Effect of nitrous oxide on gas bubble volume. PMID- 4038111 TI - Instilling ocular ointments without blurred vision. PMID- 4038112 TI - Simultaneous visualization of fundus photographs and fluorescein angiograms. PMID- 4038113 TI - Essential blepharospasm. PMID- 4038114 TI - Posterior collagenous layer. PMID- 4038115 TI - Brain-stem anesthesia after retrobulbar block. PMID- 4038116 TI - Measuring visual acuity. PMID- 4038117 TI - Apologia pro Sancta Lucia. PMID- 4038118 TI - Drusen. PMID- 4038119 TI - Vibrio alginolyticus conjunctivitis. PMID- 4038120 TI - Ocular melanoma. PMID- 4038121 TI - The mechanism of blood-retinal barrier breakdown in diabetes. PMID- 4038122 TI - Hemifacial spasm treated with botulinum A toxin injection. AB - Fifteen patients with hemifacial spasm were treated with botulinum A toxin injections. All patients experienced relief from spasm, with the effect lasting an average of 12.2 weeks. Complications were tearing in four patients, inability to close the involved eye in three patients, corneal exposure in one patient, and ectropion in one patient. All complications were transient and deemed minor by the patients. PMID- 4038123 TI - Association of hue discrimination loss and diabetic retinopathy. AB - The results of Farnsworth-Munsell 100-hue, visual acuity, and visual field testing were compared with the severity of retinopathy in a group of 90 diabetic patients. The patients showed significantly higher than expected Farnsworth Munsell 100-hue scores, with a tritanlike axis, compared with published age norms for nondiabetic individuals. The magnitude of the acquired blue-yellow hue discrimination defect correlated significantly and to a similar extent with both the severity of overall diabetic retinopathy and the severity of macular edema and hard exudate formation. Visual acuity loss correlated somewhat more significantly with macular edema than with overall retinopathy, whereas the converse was true for visual fields. For all visual function tests, the correlations were more significant for fluorescein leakage in the macula than for capillary nonperfusion in the macula. Abnormal hue discrimination was found in 65% (32/49) of eyes with proliferative diabetic retinopathy, suggesting a potential role for this test in screening for proliferative diabetic retinopathy in primary care facilities. Also, because the ability of diabetic patients with color vision deficiency to perform color-dependent tests for urinary and blood glucose may be impaired, such patients should be made aware of this potential problem. PMID- 4038124 TI - Treatment of low vision in fundus flavimaculatus. AB - Twenty-eight patients with fundus flavimaculatus were evaluated retrospectively after they had undergone examination for and treatment of low vision. Despite poor distance acuity, 27 (96%) of the patients could read 1M (20/50 reduced Snellen) or smaller print with a spectacle lens, and all patients could read standard-sized print (1M text) with some optical aid. Because such uniform improvement is uncommon among patients with low vision, we recommend examination for and trial of low-vision aids for those patients with this disorder who are having visual difficulties. PMID- 4038125 TI - Punctate outer retinal toxoplasmosis. AB - Classic ocular toxoplasmosis initially involves inner retinal layers and is associated with marked vitreous reaction. We encountered three cases of punctate outer retinal toxoplasmosis, a subset of ocular toxoplasmosis that is characterized by multifocal gray-white lesions at the level of deep retina and retinal pigment epithelium and that is associated with little or no overlying vitreous reaction. Acute lesions may resolve to form fine granular white dots. Recognition of this uncommon presentation of toxoplasmosis is important, since there is some evidence that treatment of toxoplasmosis may be effective. PMID- 4038126 TI - Postoperative diplopia and ptosis. A clinical hypothesis based on the myotoxicity of local anesthetics. AB - Postoperative diplopia and ptosis can be temporary or permanent complications in patients who have undergone ophthalmic surgery while under local anesthesia. We encountered six patients with such complications and hypothesize that some cases of postoperative diplopia and ptosis could be attributed to myotoxic effects of local anesthetics. These effects may cause the degeneration and subsequent regeneration of muscle fibers of the levator or extraocular muscles and result in temporary or permanent muscle weakness. PMID- 4038127 TI - Corneal endothelial morphology after anterior chamber lens implantation. AB - The morphologic features of the corneal endothelium were investigated by means of regional wide-field specular microscopy and computer-assisted morphometry in 13 eyes of nine patients who had undergone intracapsular cataract extraction with anterior chamber lens implantation more than one year previously. The endothelial cells in these patients demonstrated a significant increase in cellular elongation and the coefficient of variation in mean cell area and a significant decrease in the percentage of hexagonal endothelial cells when compared with age matched controls (ten eyes of ten patients). The clinical implications of these long-term morphologic changes are unknown, but the changes may be indicative of an unstable endothelium or may be an early sign of continuing cell loss. PMID- 4038128 TI - Laser iridotomy vs surgical iridectomy. Have the indications changed? AB - The number of laser iridotomies in 1982 was more than four times the annual rate of surgical iridectomies performed before the laser was in common use at the Bascom Palmer Eye Institute, Miami. No single reason accounts for the increase. Only a minority of the increase is due to a 32% increase in our outpatient volume, a backlog of individuals with borderline indications who had not undergone surgery, or the number of iridotomies performed prophylactically for asymptomatic narrow angles. The proportion of eyes treated for each of several classic indications (acute attacks, chronic angle closure with pressure elevation or synechiae, aphakic pupillary block, etc) remained the same. However, eyes with acute attacks and their fellow eyes had iridotomy more promptly and more often with the availability of laser. In addition, the laser was applied earlier in the course of chronic angle closure. We believe that the increased use of an easy, low-risk procedure represents an improvement in the quality of care. PMID- 4038129 TI - Intravenous pyogenic granuloma of the ocular adnexa. Report of two cases and review of the literature. AB - Intravenous pyogenic granuloma is a recently described form of pyogenic granuloma (PG) in which the angiomatous proliferation is confined entirely within the lumen of a vein. To our knowledge, only four cases involving the ocular adnexa, including two that we encountered, have been described. Histologically, this benign lesion is similar to PG of other locations and is characterized by lobular congeries of capillaries embedded in a fibromyxoid matrix containing scattered chronic inflammatory cells. The whole lesion appears as a single polypoid mass projecting into the lumen of a dilated vein. The histogenesis of this lesion remains obscure. Complete local excision is the treatment of choice. Intravenous PG can be differentiated from other intravascular fibroangiomatous proliferations, including intravascular papillary endothelial hyperplasia, intravenous atypical vascular proliferation, intravascular fasciitis, and organized thrombus. PMID- 4038130 TI - Rat extraocular muscle regeneration. Repair of local anesthetic-induced damage. AB - Local anesthetics that are commonly used in ophthalmic surgery (0.75% bupivacaine hydrochloride, 2.0% mepivacaine hydrochloride, and 2.0% lidocaine hydrochloride plus 1:100,000 epinephrine) were injected into the retrobulbar area of rat eyes. Controls were injected with physiological saline. All three anesthetics produced massive degeneration of the extraocular muscles. Muscle degeneration is followed by regeneration of the damaged muscle fibers. In addition to muscle damage, severe damage was also seen in harderian glands, especially after exposure to mepivacaine and lidocaine plus epinephrine. With these findings in rats, it is hypothesized that the temporary diplopia sometimes seen in patients after ophthalmic surgery might be due to anesthetic-induced damage to the extraocular muscles. PMID- 4038131 TI - Posterior capsule opacification. An in vitro model. AB - Posterior capsule opacification results from migration of lens epithelial cells onto the posterior capsule, where they produce collagen and contract to cause wrinkling of the capsule. We have designed an in vitro model that reproduces the process of opacification. Lens capsules removed from enucleated bovine eyes are placed within specially designed holders, creating a culture dish with the capsule as its bottom surface. Albino rabbit lens epithelial cells are then plated on the capsule. These capsules develop clinical and ultrastructural features of opacification very similar to those observed in humans. Membranes composed of confluent epithelial cells closely resemble the cellular membranes observed with specular microscopy in human patients. Transmission electron microscopy demonstrates that a membrane several cells thick forms on the capsules. This model allows careful morphologic, metabolic, and biochemical studies of the process of opacification and the investigation of therapies designed to prevent opacification of the posterior capsule. PMID- 4038132 TI - Experimental vitrectomy. A lens-sparing technique in the rabbit eye. AB - We describe a technique for experimental vitrectomy in the rabbit eye, in which the lens remains intact and the postoperative intraocular inflammatory response is minimized. In comparison with combined vitrectomy and lensectomy, our technique allows the fundus to remain visible for follow-up from the very first postoperative day; traction retinal detachment does not develop as a late complication. We also describe a simple method for gross identification and estimation of the amount of residual vitreous gel on the retinal surface. PMID- 4038133 TI - Evaluation of bromovinyldeoxyuridine-related compounds in the treatment of experimental herpes simplex keratitis. AB - Several newly synthesized compounds, all structurally related to the highly potent and selective antiherpes agent bromovinyldeoxyuridine ( [E]-5-[2 bromovinyl]-2'-deoxyuridine), have been evaluated for their healing effect on herpes simplex virus type 1 keratitis in rabbits. These novel compounds included chloroethyldeoxyuridine (5-[2-chloroethyl]-2'-deoxyuridine), trifluoropropenyldeoxyuridine ( [E]-5-[3,3,3-trifluoro-1-propenyl]-2' deoxyuridine), bromovinylaminodideoxyuridine ( [E]-5-[2-bromovinyl]-3'-amino 2',3'-dideoxyuridine), bromovinylarabinofuranosyluracil ( [E]-5-[2-bromovinyl]-1 beta-D-arabinofuranosyluracil), and glycylbromovinyldeoxyuridine (5'-O aminoacetyl-[E]-5-[2-bromovinyl]-2'-deoxyuridine). Bromovinylaminodideoxyuridine and trifluoropropenyldeoxyuridine did not promote a significant healing of herpes simplex keratitis. Bromovinylarabinofuranosyluracil markedly reduced the severity of keratitis, but to a significantly lesser extent than bromovinyldeoxyuridine. Finally, chloroethyldeoxyuridine and glycylbromovinyldeoxyuridine caused a pronounced healing effect on herpes simplex keratitis, comparable to that obtained with bromovinyldeoxyuridine. Chloroethyldeoxyuridine was even slightly better than bromovinyldeoxyuridine, but the difference in their healing effect was not statistically significant. PMID- 4038134 TI - Fluorouracil (5-FU) and cytarabine (ara-C) inhibition of corneal epithelial cell and conjunctival fibroblast proliferation. AB - We evaluated the antiproliferative properties of fluorouracil (5-FU) and cytarabine (ara-C) in a tissue culture model of rabbit corneal epithelial cells and conjunctival fibroblasts. Cells were treated with fluorouracil or cytarabine for five days. Corneal epithelial cell proliferation was inhibited to 50% of control proliferation by 0.6 mg/L of fluorouracil or 30 micrograms/L of cytarabine. Proliferation of conjunctival fibroblasts was inhibited to 50% of control by 0.5 mg/L of fluorouracil or 50 micrograms/L of cytarabine. The antiproliferative effect of 10 mg/L of fluorouracil was not blocked by thymidine. The inhibition of proliferation produced by 100 or 1,000 micrograms/L of cytarabine was blocked by 2'-deoxycytidine at concentrations of 10(-5) M and 10( 4) M, respectively. The antiproliferative effects of fluorouracil and cytarabine appear similar for both cell types. Blockage of cytarabine-related ocular toxic effects may be possible with 2'-deoxycytidine. PMID- 4038135 TI - Vitreous aspirates from patients with proliferative vitreoretinopathy stimulate retinal pigment epithelial cell migration. AB - Several studies have focused on retinal pigment epithelial (RPE) cell proliferation as an important event in proliferative vitreoretinopathy (PVR). Little attention has been given to the question of how RPE cells gain access to the vitreous cavity where proliferation occurs. We have recently demonstrated that the serum components fibronectin and platelet-derived growth factor stimulate and direct RPE migration in vitro. In this study, we used this same in vitro technique to examine vitreous aspirates from 13 eyes with PVR, five eyes with macular puckers, and three eyes with uncomplicated retinal detachments for their ability to stimulate RPE migration. We found that aspirates from eyes with PVR stimulated RPE migration to a much greater extent than aspirates from eyes with macular pucker and uncomplicated retinal detachments. The ability to stimulate RPE cell migration correlated with high levels (mean +/- SEM, 178 +/- 67 mg/L) of immunoreactive fibronectin. PMID- 4038136 TI - Functional endoscopic sinus surgery. Technique. AB - The purpose of functional endoscopic sinus surgery is to reestablish ventilation and mucociliary clearance of the sinuses. This goal is achieved primarily by the endoscopic removal of disease from key areas of the anterior ethmoid and middle meatus. In addition, the technique also offers the possibility of performing sphenoethmoidectomy with preservation of the middle turbinate. Localized irreversible disease in the maxillary sinus may be removed endoscopically with minimal trauma. The technique allows excellent visualization, and results in minimal morbidity and bleeding. Nasal packing is not required, and surgery can usually be performed on an outpatient basis using local anesthesia. PMID- 4038137 TI - Diagnosis and management of obstructive sleep apnea. Part II. AB - Snoring has been shown to be the primary sign of a potentially serious medical condition, ie, obstructive sleep apnea. Traditionally, the otolaryngologist has been the primary resource for patients with snoring problems although, until recently, little was known about the now-acknowledged serious complications of this phenomenon. Among the primary treatments for this condition, the most commonly used to-date involve surgical procedures routinely performed by the otolaryngologist, ie, tracheostomy and uvulopalatopharyngoplasty. Thus, the practicing otolaryngologist has been thrust into the forefront of diagnosis and management of obstructive sleep apnea, and it behooves the modern practitioner to be cognizant of the multidisciplinary approach to the diagnosis and management of this problem. The utilization of information obtained during the sleep study determines the management of the sleep apneic patient. PMID- 4038138 TI - Indications for palatopharyngoplasty. AB - A retrospective study of 30 patients was undertaken to evaluate the effectiveness of palatopharyngoplasty (PPP) for the treatment of obstructive sleep apnea (OSA). Results indicated that PPP is effective in the treatment of snoring but has a limited effect on the major indices of OSA syndrome. Thus, only 23% of the patients had a significant reduction in sleep-related apnea episodes and a reduction in the oxygen saturation deficit. An additional 23% showed some improvement in these indices. The procedure failed in the remaining 54% of the population studied. The greatest success with PPP was achieved in the patients with moderate OSA in whom fiberoptic and craniometric evaluation indicated that the obstruction was centered at the level of the velopharyngeal sphincter. PMID- 4038139 TI - Malignant salivary gland tumors of the base of the tongue. AB - Malignant salivary gland tumors of the base of the tongue are unusual lesions and optimal treatment has not been established. As a group, these tumors tend to be diagnosed at an advanced stage, and consequently carry a grave prognosis. Fourteen patients were treated at UCLA between 1954 and 1984. Twenty-three percent of the patients have survived longer than ten years, although only one patient is free of disease. Eight of 14 patients developed distant metastases. Salivary tumors in this location are difficult to completely excise and surgical margins are frequently positive. Treatment using a planned combined approach is advocated. PMID- 4038140 TI - Near-total pharyngeal reconstruction by 'rotary-door' sternohyoid myocutaneous flap in the dog. A preliminary report. AB - Closure of the pharyngoesophagus after total laryngectomy or partial pharyngectomy is not a difficult problem in most cases. Primary suture repair of the defect is usually adequate, providing sufficient healthy mucosa is available. When this is not feasible, it may be necessary to mobilize tissue from distant sites. The deltopectoral and various myocutaneous flaps are often chosen for this purpose because of their reliability and versatility. Unfortunately, they necessitate either two-stage surgery or involve excessive bulk, and both methods result in unsightly defects, especially in women. The "rotary-door" sternohyoid myocutaneous flap avoids these drawbacks, while utilizing tissues within the surgical field in a single-stage procedure. Seven mongrel dogs underwent total laryngectomy and partial pharyngectomy. The pharyngeal defect was closed with a rotary-door sternohyoid myocutaneous flap. Three dogs had an uneventful recovery and two developed fistulae that closed spontaneously within three weeks of surgery. The pharyngocutaneous repair was found to be intact on postmortem examination. PMID- 4038141 TI - Profile analysis in facial plastic surgery. AB - We devised a simple and reliable method of profile analysis for facial plastic surgery. Profile photographs are taken with the natural head position technique. Key cephalometric landmarks are then identified and digitalized from either photographs or slides, using a digitalizer with a resolution of 0.001 in. The digitalizing pad is connected to a microcomputer. The menu-driven software allows selection of multiple functions from different cephalometric systems. Data can be stored on disk for future analysis. The method is useful in preoperative planning and postoperative evaluation of facial plastic surgery procedures. PMID- 4038142 TI - Total ophthalmoplegia after internal maxillary artery ligation. AB - Total ophthalmoplegia is a serious complication of internal maxillary artery ligation. Although serious complications of transantral surgery of the pterygopalatine space are rare, they remain a very real possibility and should be considered before undertaking arterial ligation for treatment of posterior epistaxis. PMID- 4038143 TI - Intramuscular myxoma of the neck. AB - Intramuscular myxomas are extremely rare tumors in the neck. In reviewing the world literature, we found a total of five cases of intramuscular myxoma that occurred in the head and neck region. The purpose of this study is to report an unusual case of intramuscular myxomas that were found bilaterally in the digastric muscles of a girl who presented with a painless palpable mass in the neck. PMID- 4038144 TI - Pathologic quiz case 2. Warthin's tumor arising in a lymph node containing heterotopic salivary gland. PMID- 4038145 TI - Pathologic quiz case 1. Neuroendocrine carcinoma of the skin (Merkel's cell tumor, trabecular carcinoma of the skin). PMID- 4038146 TI - Pharyngoesophageal reconstruction. PMID- 4038147 TI - Medial shifting of the canine vocal cord by injection of isolated chondrocytes. AB - In the search for new materials to fill the unilaterally paralysed vocal cord, auto- and allogeneic chondrocytes were isolated from costal cartilage, and were injected into the canine vocal cord. The produced cartilage caused a thickening and shift of the treated cord towards the median line of the glottis. Such changes occurred in all autogeneic transplants, and persisted for the period of observation (up to 6 weeks). In allogeneic transplants, the effect was present after 6 and 12 weeks, but disappeared after 18 weeks. Cartilage produced by the autogeneic chondrocytes persisted at the site of injection without any signs of resorption. In contrast, allogeneic cartilage became surrounded by infiltrating cells and was slowly resorbed to disappear completely between the 12th and 18th weeks of observation. Immunosuppressive treatment of some of the allogeneic chondrocyte recipients reduced the lymphocytic infiltrations occurring, and inhibited the resorption of the reconstructed cord cartilage. Discontinuation of the immunosuppression, however, resulted in subsequent graft loss. PMID- 4038148 TI - Failures in myringoplasty. AB - We analyzed those failures occurring in 417 myringoplasties. Forty-four drum re perforations were found (10.6%), half of which occurred immediately after operation. Causes of these early failures included necrosis in the middle of the graft without infection (10 ears) and blunting of the anterior margins of the graft (7 ears). Infection was the most common cause of re-perforations in the later failures. Re-perforations also occurred more frequently when larger perforations were closed in contrast to repair of small ones. We found that other pre-operative factors ("dry" or "wet" ear, site of the perforation) or grafting technique ("underlay" or "overlay") did not affect the graft take-rate. Adhesive eardrums were found in 23 ears (5.5%). These were more common when ears were infected pre-operatively, when middle ear mucosa was removed during the primary operation, or when squamous epithelium was present on the tympanic mucosa. Lateralization of the grafted eardrum was found in two cases (0.5%), both of which had been operated on using the sandwich technique. PMID- 4038149 TI - Frequency composition of spontaneous cochlear emissions. AB - Spontaneous cochlear emissions consist of one or more sinus tones. Oscillations and frequency shifts clearly widen averaged traces. Multiple peaks, if present, are spaced at intervals of 2-3% of the frequency, and increase with frequency. A frequency jump by the same amount was seen in one case. This appears to represent the distance between hair cells, and suggests that individual hair cells play a leading role in these oscillations. PMID- 4038150 TI - Temporary threshold shift frequency profiles after low-tone exposure. AB - Low-tone exposure elicits four distinct dips in hearing thresholds: one octave above the exposure frequency, in the permanent threshold shift (PTS) range, at about 10-11 kHz, and at 14-15 kHz. While dips 1, 2 and 3 decay as a function of the time log, dip 4 has a much longer decay time. PMID- 4038151 TI - Measurement of tonsillar blood flow in normal and pathological conditions by the use of the 133Xe clearance technique. AB - By using the 133Xe clearance technique, we measured the blood flow to the human palatine tonsil in 10 normal volunteers, 11 patients with chronic tonsillitis, and 11 with hypertrophic tonsils. We found that the mean blood flow was 30.08 +/- 5.39 ml/ 100 g per min in normal tonsils, 17.06 +/- 3.72 in chronic tonsillitis and 49.50 +/- 9.30 in hypertrophic tonsils. Our results show a statistically significant decrease in blood flow in chronic tonsillitis (P less than 0.01) and a significant increase in hypertrophic tonsils (P less than 0.01) when compared to the normal controls. The difference between the blood flow in chronic tonsillitis and hypertrophic tonsils was also statistically significant (P less than 0.01). In all three groups studied, no statistically significant difference was observed in the blood flow to the right and left tonsils (P greater than 0.05). PMID- 4038152 TI - The effect of flavone treatment on human otosclerotic ossicle organ cultures. AB - We studied the effect of 7-isopropoxy-isoflavone (Ipriflavone) on the collagen synthesizing activity in human otosclerotic auditory ossicle samples from whole organ cultures during incubation for 96 h, and compared this effect with that found in normal meatal cortical bone. Ipriflavone led to a dose-dependent increase in the collagen synthesizing activity in both the healthy and the otosclerotic bone samples. At the highest Ipriflavone concentration used (50 microM), collagen synthesis increased 6-fold in the cortical bone and 9-fold in the otosclerotic bone, as compared with untreated controls. These findings indicate that the otosclerotic bone cavities are filled in vitro with organic matrix. PMID- 4038154 TI - The endolymphatic sac in the Mondini disorder. AB - The endolymphatic sacs are described in temporal bone specimens from a 31-year old man with bilateral Mondini disorder. The ducts and sacs are thin-walled, cyst like structures with complete absence of loose vascular perisac tissue, and are directly apposed to the bone of the vestibular aqueduct. Histological evidence of severe bone erosion is present in these specimens and is most marked in the intermediate and distal portions of the vestibular aqueduct. It is also present in the foveal region of the posterior temporal bone surface underlying the sac. Erosion of the bony wall of the paravestibular canaliculus (PVC) is demonstrable, with incorporation of the vein of the PVC inside the margin of the widened vestibular aqueduct. These findings suggest a causal relationship between pressure within the endolymphatic duct and sac and erosion of the surrounding bone. The absence of endolymphatic hydrops of the cochlea and vestibular organs in the Mondini disorder contrast significantly with the endolymphatic hydrops seen in Meniere's disease. PMID- 4038153 TI - A rarely observed case of primary multiple carcinomas of the head and neck. AB - We report a 71-year-old male patient with five separate primary metachronous squamous cell carcinomas of the head and neck (parotid, tongue, soft palate, larynx and hypopharynx) that occurred over a period of 8 years. The long survival of the patient after discovery of his first neoplasm (parotid) is the result of careful vigilance during the follow-up period and diligently planned therapies for each of his multiple primary tumors after radical surgery had been performed on his first neoplasm. PMID- 4038155 TI - The influence of masking on the ipsi- and contralateral brainstem evoked potential. AB - We have examined clinically and experimentally the masking effects of white noise in registering brainstem evoked potentials and determining the Jewett-wave V. We studied input-output functions as well as latency periods of evoked potentials with masking of non-stimulated contralateral ears in 18 children aged 5-14 years. When differences of 50 dB or more were found between stimulation and masking, the Jewett-wave V could be partially suppressed. Other changes observed included alterations in potential and phase, as well as shifts in the latency period of the potentials. The clinical importance of the measurements determined indicates that findings may be used in examining patients with unilateral sensory hearing impairments to formulate possible differential diagnoses. PMID- 4038156 TI - Serum lipids in the People's Republic of China. Comparison of Western and Eastern populations. AB - Serum cholesterol and HDL cholesterol levels were measured in an urban and a rural population of the People's Republic of China and compared with cholesterol values obtained in Belgium and in the Republic of Korea, with use of the same methodology. Total cholesterol levels were markedly lower in the People's Republic of China than in Belgium and generally lower than in Korea, both in male and female subjects. However, the differences in HDL cholesterol levels among the three populations were small in males and only significantly higher in Belgium in the age classes below 34 years. In women of all age groups, HDL cholesterol values were significantly higher in Belgium than in China and Korea. Total cholesterol levels below 100 mg/dl were found in the People's Republic of China in about 2% of the participants. Apolipoprotein B was significantly lower, and the apolipoprotein A1/B ratio was significantly higher, in China and Korea compared to Belgium. PMID- 4038157 TI - Direct fetal blood examination for prenatal diagnosis of homozygous familial hypercholesterolemia. AB - Prenatal diagnosis of homozygous hypercholesterolemia was achieved at the 24th week of gestation by analysis of lipid values in a fetal blood sample obtained by a needle guided by ultrasound. These abnormal values were compared to values in blood obtained from normal fetuses at the same stage of gestation. After abortion, the diagnosis was confirmed by measuring LDL receptor activity on fibroblast cultures from a skin biopsy. The main advantages of this procedure over measuring LDL receptor activity on cultured amniotic cells are its simplicity and speed. PMID- 4038158 TI - Effect of plasma proteins on endothelial binding and vesicle loading of anionized ferritin in rabbit aorta. AB - Endothelial binding and vesicle loading of anionized ferritin (AF, isoelectric point, 3.8 to 4.2) in plasma and in Tyrode's solution were investigated in the rabbit aorta. After 2 minutes of in situ perfusion, binding to vesicle necks was significantly higher than elsewhere on the membrane and was independent of AF concentration in the range of 0.05 g/ml to 0.2 g/ml for both perfusates. After 30 minutes, no particles were seen in abluminal vesicles and few had reached the basement membrane. Compared to AF in plasma, AF in Tyrode's solution showed lower endothelial binding and greater vesicle loading (p less than 0.005). The average number of particles per loaded vesicle was equal to the average particle density at vesicle necks in Tyrode's solution, but not in plasma, for 0.1 g/ml AF. Gel chromatography and electrophoresis demonstrated no detectable difference between AF particles incubated in plasma or Tyrode's solution. Our experiments indicate that adherence to, or entrapment in, the glycocalyx is an important step for molecules that are transported by vesicles. We hypothesize that plasma proteins adsorb to the endothelial surface and partially shield its net negative charge so that more AF may bind. Plasma proteins also inhibit vesicle loading either sterically or by modifying the electrical potential at the vesicle neck compared to that within the vesicle cavity. PMID- 4038159 TI - Triglyceride-lowering effect of marine polyunsaturates in patients with hypertriglyceridemia. AB - Twenty male patients with primary hypertriglyceridemia were treated for 4 weeks with daily supplements (15 g) of oil, which provided approximately 6 g of polyunsaturated fatty acid (PUFA) either of fish or of vegetable origin. Total plasma cholesterol concentrations were unaffected, but both types of supplement increased high density lipoprotein-3 (HDL3) cholesterol concentrations. The fish, but not the vegetable, oil supplement led to a decrease in plasma triglyceride concentrations. Very low density lipoprotein (VLDL), fatty acid composition, and VLDL triglyceride kinetics were subsequently studied in five patients (four male, one female) before and after 4 weeks of therapy with 15 g of the same fish oil. The fish oil led to increases in the proportion of eicosapentaenoic acid in both the VLDL triglyceride and phospholipid fractions, but the increase was greater in the latter. In contrast, the proportion of docosahexanoic acid was increased only in the VLDL triglycerides. The decrease in plasma triglyceride concentrations that occurred with fish-oil therapy was accompanied by a reduction in the absolute catabolic rate of VLDL triglyceride, implying a concomitant change in synthetic rate; the fractional catabolic rate of VLDL triglyceride was unaltered. It is suggested that polyunsaturated fatty acids of marine origin may be therapeutically useful for hypertriglyceridemia. PMID- 4038161 TI - [Intercultural research of drinking between Japanese-American and mainland Japanese (1). Drinking pattern and problem drinking]. PMID- 4038160 TI - Demographic, behavioral, biochemical, and dietary correlates of plasma triglycerides. Lipid Research Clinics Program Prevalence Study. AB - Few studies have simultaneously examined the relationship of triglyceride levels with a wide variety of potential covariates. Thus, the present study was designed to assess in a large, free-living population the association of fasting plasma triglyceride values with selected demographic, behavioral, biochemical, and dietary measures. These analyses were done using data obtained from 5189 white men and women aged 20 to 69 years who participated in the Lipid Research Clinics Program Prevalence Study. Of the eight nondietary factors examined, age, Quetelet Index, fasting plasma glucose, and cigarette smoking were strongly, positively associated (p less than 0.0001) with triglycerides in men and in women not using gonadal hormones. Among women using oral contraceptives or estrogens, only Quetelet Index (p less than 0.01) and cigarette smoking (p = 0.01) were significantly related to triglyceride values. Physical activity was inversely associated (p less than 0.0001) and use of diuretic medications was positively related (p less than 0.01) to triglycerides only in men. Results of analyses of triglycerides and six selected dietary measures varied by age, sex, and hormone use subgroups. Although none of the dietary variables showed consistent associations with triglycerides across all of the subgroups, triglycerides tended to be inversely associated with total calories per kilogram of body weight and the percentage of calories as dietary fat. PMID- 4038162 TI - [Intercultural research of drinking between Japanese-American and mainland Japanese (2). Banshaku drinking and party (Enkai) drinking]. PMID- 4038163 TI - [Determination of salsolinol by gas chromatography-mass spectrometry and influence of foods on urinary salsolinol excretion]. PMID- 4038164 TI - [Epidemiological study on alcohol drinking patterns in Tochigi Prefecture]. PMID- 4038165 TI - [Central pontine myelinolysis on alcoholism: report of an autopsy case]. PMID- 4038166 TI - [Pattern classification of problem drinking behaviors among female college student drinkers]. PMID- 4038167 TI - [Studies on the individual differences of ethanol preference and ethanol metabolism in the rat]. PMID- 4038168 TI - Acetaldehyde metabolism in liver injury. PMID- 4038169 TI - Mid-trimester therapeutic abortion by vaginal suppository of 16, 16-dimethyl trans-delta 2-prostaglandin E1. PMID- 4038170 TI - Unexplained menorrhagia: problems with management. PMID- 4038171 TI - Some characteristics of breech deliveries. PMID- 4038172 TI - Multivariate analysis of Singapore birth weights. PMID- 4038173 TI - Sirenomelia--a case report. PMID- 4038174 TI - Uterine malignancy developing after a long term use of IUCD. Additional report of a case: association of endometrial stromal sarcoma with IUCD. PMID- 4038175 TI - Hysterosalpingography. 1. The incidence of tubal spasm during hysterosalpingography. PMID- 4038176 TI - Hysterosalpingography. II. The efficacy of glucagon as a spasmolytic in overcoming tubal spasm during hysterosalpingography. PMID- 4038177 TI - A clinico-pathological diagnosis of hypertensive disorders of pregnancy. PMID- 4038178 TI - The management of female hirsutism with the anti-androgen agent cyproterone. PMID- 4038179 TI - Fetal weight and premature rupture of the membranes in preterm delivery. PMID- 4038180 TI - Choriocarcinoma coexisting with adenocarcinoma in the pars interstitialis of the oviduct: a case report. PMID- 4038181 TI - Correlation between amniotic fluid lecithin-sphingomyelin (L/S) ratio and optical density measured after centrifugation at varying forces. PMID- 4038182 TI - Quality assurance in a multidisciplinary group. Priority setting in an intensive care unit. PMID- 4038183 TI - The use of antimicrobials in a maternity unit: a retrospective study. PMID- 4038184 TI - Performance appraisal of the board and chief executive officer at the Port Augusta Hospital. PMID- 4038185 TI - Draft Privacy Bill 1983. Access to records of personal information. PMID- 4038186 TI - What do the figures show? ACHS 1974-1984: a decade of progress. PMID- 4038187 TI - Notes for nursing homes. PMID- 4038188 TI - Medical problems in hospitals: what has the Australian Council on Hospital Standards discovered? PMID- 4038189 TI - Doctors, physiotherapists, chiropractors and the issue of spinal manipulation. PMID- 4038191 TI - When to treat 'mild' hypertension. PMID- 4038190 TI - Hypertension in general practice. A survey of adequacy of control, investigation and follow up. PMID- 4038192 TI - Commencing antihypertensive therapy. PMID- 4038193 TI - Hypertension. PMID- 4038194 TI - Presentations of early symptoms of multiple sclerosis. PMID- 4038195 TI - Styles of doctoring and models of health. Some side effects of the doctor. PMID- 4038196 TI - General practitioners and the health centre. Is there a meeting point? PMID- 4038197 TI - Aboriginal child health. PMID- 4038198 TI - Weekend use of a children's casualty department by patients who have private doctors. PMID- 4038199 TI - The importance of consent to treatment. PMID- 4038200 TI - Resident medical practitioners in private hospitals. PMID- 4038201 TI - Speargun injury. PMID- 4038202 TI - Australia's hospital population by the year 2011. PMID- 4038203 TI - Reversible nutritional myopathy with myotonia in the protein-deficient rat given methionine. AB - Rats fed a protein-deficient synthetic diet developed hind limb weakness caused by a myopathy with myotonic features on electromyography. Deficiency of vitamin E and selenium, known causes of nutritional myopathy, were excluded. Methionine supplementation of the diet reversed the clinical signs of weakness within 12 h. PMID- 4038205 TI - Multiparity and sex ratio in mice. PMID- 4038204 TI - Cannulation of the cisterna magna in sheep: a method for chronic studies of cerebrospinal fluid. AB - A method of cannulating the cisterna magna of sheep is described. Successful cannulations were achieved in 15 of 17 attempts (88%). Mean cannula patency was 13.9 days (range 7-20). Using these cannulas, it was possible to obtain samples of cerebrospinal fluid (CSF) in large volumes (4-8 ml) and remove 20-30 ml of CSF over a 5 h period. This technique allows access to the CSF of an animal large enough for the removal of samples of CSF of sufficient size to detect materials present at very low concentrations. PMID- 4038206 TI - Acute deletion of arterial baroreceptor input in the conscious rabbit. AB - We describe the use of a snare to denervate the carotid sinus in conscious rabbits whose other arterial baroreceptors had been denervated 8-14 days previously by surgical operation. Within 2 min of tightening the snare arterial blood pressure had risen from 81 +/- 2 to 119 +/- 5 mmHg, and heart rate had risen from 214 +/- 9 to 280 +/- 9 beats min-1. They remained at these high levels for 15 min but then fell, so that after 30 min blood pressure and heart rate were 103 +/- 9 mmHg and 265 +/- 8 beats min-1 respectively. They declined somewhat further, but irregularly, over the succeeding 7 days. The previously brisk baroreceptor-heart rate and carotid sinus reflexes were abolished by ensnaring the carotid sinus nerve, and remained absent over the succeeding 7 days. This method of deleting input from the arterial baroreceptors is not confounded by general anaesthesia or surgical injury, and allows observations to be made within minutes. The rapid decline in blood pressure and heart rate after 15 min, and the subsequent slow downward trend, are unexplained. They are of potential importance in experiments designed to quantitate the effects of baroreceptor input on the circulation. We also noted that, whereas spontaneous activities of the baroreceptor-intact rabbit were usually associated with transient rises of blood pressure and heart rate, after deletion of baroreceptor input the same activities were usually associated with transient falls. PMID- 4038207 TI - Autoradiographic demonstration of deoxyglucose uptake in guinea pig cochlea. AB - The 2-deoxyglucose autoradiographic method was applied to whole-body cryosectioning to include the cochlea. The highest levels of 2-deoxyglucose uptake were observed in the vascular stria, spiral ligament and spiral prominence. The cochlear nerve showed the next highest level of uptake, while the organ of Corti and the spiral ganglion showed low levels. The functional significance of the results was briefly discussed. PMID- 4038209 TI - Subperiosteal orbital hemorrhage associated with chronic sinusitis: a case report and review of the literature. AB - A case of subperiosteal orbital hemorrhage associated with chronic sinusitis is reported. A 57-year-old woman had a sudden onset of severe orbital pain and exophthalmos in the left eye. Computed tomography revealed a discrete round mass in the left retro-orbital space. An external frontoethmoidectomy was performed to evacuate the hematoma of the subperiosteal space. Additionally, the mucosa was edematous in the left ethmoid sinus. It appears that subperiosteal orbital hemorrhage in this case was caused by rupture of vessels which were inflamed as a result of sinusitis. Orbital hemorrhage associated with chronic sinusitis has rarely been reported. Diagnosis and treatment are discussed and etiologic factors are reviewed. PMID- 4038208 TI - A case of periodic alternating nystagmus: with a special reference to the efficacy of baclofen treatment. AB - A case of periodic alternating nystagmus (PAN), probably of congenital type, was reported. A 25-year-old woman, who has been suffering from cerebral palsy, was referred to our clinic for the consultation of a peculiar nystagmus and intermittent oscillopsia. Electronystagmographic examination revealed that the horizontal nystagmus on straight ahead gaze in the light continuously changed its direction alternately about 110 sec in right direction and about 90 sec in left direction with about 5 sec of an interlude, during which no nystagmus was observed, between each span. Electronystagmographic recording also illustrated that the amplitude and slow phase eye velocity of PAN first increase and then decrease in each span. Since other various kind of examination including neuroradiological examination revealed no special abnormality except for the signs of cerebral palsy, congenital PAN was suspected in this case. Although previous report indicated that baclofen dose not control congenital PAN in contrast to that of acquired type, we tried baclofen in this case. Baclofen reduced the strength of the nystagmus remarkably and patient also recognized the considerable improvement of her oscillopsia. We are of the opinion that the baclofen may improve the strength of congenital PAN and oscillopsia as well as those of acquired type PAN. PMID- 4038210 TI - A study of the nerve endings of the outer hair cells in the organ of Corti--using scanning electron microscopy. AB - The nerve endings on the outer hair cells of the guinea pig organ of Corti were studied using a scanning electron microscope. The nerve endings in the basal turn were entirely exposed in the space of Nuel, whereas in the upper turns almost all nerve endings were covered by the Deiters' cell bulge. The number and the size of the nerve endings gradually decreased from the basal turn toward the apical turn. The shape of the nerve endings was spindle-shaped in the basal turn, while it was round in the upper turn. Some nerve endings were found to locate close to the outer hair cell surface. No pathological change was observed in the nerve endings 25 hr after completion of series treatments of streptomycin or kanamycin. However, the outer hair cells consistently showed shrinkage, especially in the basal turn. PMID- 4038211 TI - Metastases to the Rouviere nodes and headache. AB - This paper presents two cases of Rouviere node metastasis in carcinoma of the hypopharynx as confirmed by gallium scintigraphy. Invasion of the Rouviere nodes was clarified within six months of the onset of symptoms in both cases. One patient eventually died of intracranial cancerous invasion and the other remains in the terminal stage of cancer with multiple bone metastases. It was hitherto believed that metastases to the Rouviere nodes were extremely difficult to diagnose in the early stages. However, it is now apparent that the neurological signs and symptoms which commonly appear in patients with cancerous invasion of the jugular foramen syndrome facilitate early diagnosis of the disease, the most common symptom being a headache. PMID- 4038212 TI - The harmful effects of noise in a children's ward. AB - Because of concerns frequently expressed by members of staff about the annoyance caused by noise in a children's ward, noise levels were measured. These confirmed that ambient and peak levels were well in excess of levels recommended for hospital wards and were often above those recommended for average outdoor situations. The harmful effects of noise in general are discussed with regard to annoyance and the effects on hearing, performance, accident rates, social relationships and sleep. Interviews with members of ward staff confirmed a high degree of worry about noise levels and revealed that machines for ward cleaning were the most annoying noise source, followed by the crying of infants. Patients and parents probably suffer similar annoyance and distress from noise. Possible harmful effects on patients are discussed and measures to reduce noise levels in wards are suggested. PMID- 4038213 TI - Tests for autonomic neuropathy in diabetic children. AB - Five simple tests of autonomic nerve function were studied in 38 children (12.0 years, s.d. = 3.3) with insulin-dependent diabetes mellitus and a further 38 age and sex matched controls in order to validate the use of these tests in children. The five tests included one test (immediate heart rate response to standing) previously reported. Compared to controls, diabetics showed a significantly faster heart rate at rest (P = 0.022), a reduced heart rate variation during quite respiration (P = 0.003), a smaller change in heart rate following a single deep breath (P = 0.006), a lower Valsalva ratio (P = 0.084) and a lower maximum R R/minimum R-R ratio in response to standing (P = 0.033). The heart rate response to the Valsalva manoeuvre is less suitable for use in children than adults as it requires considerable co-ordination and co-operation and it did not correlate with the other tests of autonomic nerve function. The other tests significantly correlated with each other and were quick and easy to perform. They required no special co-operation and required no special equipment other than a standard ECG machine. Three diabetics had abnormalities in four of the tests (mean heart rate, heart rate variations during quiet respirations, change in heart rate produced by a single deep breath and the previously reported immediate heart rate response to standing). None of the controls had abnormalities in more than two of the tests. PMID- 4038214 TI - Renal abnormalities and spondylometaphyseal dysplasia. AB - A renal lesion has not been previously described in association with spondylometaphyseal dysplasia. A case of nephrotic syndrome with progression to renal failure from focal segmental glomerulosclerosis is described. PMID- 4038216 TI - Cystic fibrosis heterozygotes have normal autonomic innervation of the heart. AB - Five simple tests of autonomic nerve function based on measurements of cardiovascular responses to various stimuli were used to investigate possible autonomic dysfunction in obligate heterozygotes for cystic fibrosis. There were no significant differences between the heterozygotes and control groups in any of the tests, suggesting that cystic fibrosis heterozygotes have normal autonomic innervation of the heart. PMID- 4038215 TI - Sacrococcygeal teratoma. AB - Eight cases of sacrococcygeal teratoma are described. Seven patients were diagnosed at birth, and one presented at 3 1/2 months of age with urinary retention. Two patients had associated congenital anomalies (arachnoid cyst, external angular dermoid and bifid sacrum), while one had a family history of sacrococcygeal teratoma. All had the tumour removed together with the coccyx as soon as the diagnosis was made. None had recurrence of the tumour. PMID- 4038217 TI - Pulmonary actinomyces in a child. AB - Pulmonary actinomycosis is rare in Australian children. A patient with the condition is described in whom a diagnosis was made by open lung biopsy. She was treated successfully with penicillin and tetracycline. PMID- 4038218 TI - Truncus arteriosus and facial dysmorphism. AB - Facial features of infants with truncus arteriosus were photographed and reviewed. Anomalies included hypertelorism, low set ears, micrognathia, down slanting palpebral fissures, short philtrum and small mouths. Associated cardiovascular defects were interrupted aortic arch, double aortic arch, right aortic arch and aberrant brachiocephalic vessels. Potential teratogenic factors included maternal diabetes, syphilis, alcohol ingestion, carbimazole therapy and infant chromosomal anomalies. The facial features, together with the rare cardiac abnormalities of truncus arteriosus and aortic arch defects are similar to those described in Di George syndrome (defect of fourth branchial arch and derivatives of third and fourth pharyngeal pouches). However none of these patients had symptomatic hypocalcaemia or absence of the thymus. It is concluded that this association of truncus arteriosus, aortic arch abnormalities and facial anomalies involves first and fourth branchial arch maldevelopment, and indicates embryological insult between the fourth and seventh weeks of gestation. PMID- 4038219 TI - Recommendation from Australian Radiation Laboratory. Radiological examination of women of reproductive capacity. AB - The National Health and Medical Research Council, at its 97th Session (June 1984) modified one of its earlier recommendations relating to the radiological examination of young women. This was made on the recommendation of its Radiation Health Committee and the Council have requested publication of the new recommendation so that all people who prescribe radiological examination should be aware of the Council's recommendation. With the mean age of menarche in Australian girls now being before their 13th birthday, a substantial proportion of a paediatric population will be affected by these recommendations. PMID- 4038220 TI - The importance of the lymphatic system. PMID- 4038221 TI - Auditory brainstem evoked response. PMID- 4038222 TI - Secular trends in fatal and disabling child trauma. AB - Types and rates of childhood accidents are constantly varying. From the point of view of the potential child victim, the danger-safety equilibrium is disturbed by changes in lifestyles, availability of new consumer goods, and changes in social order. Balance is achieved by the implementation of preventive measures, particularly safety legislation. 'Old' hazards affecting children in pre industrial societies can re-emerge at any time as wealthy sophisticated societies aspire to recapture the delights of open space, the water, and 'country-style' living. Age-specific fatal accident rates are given for Australian children for the period 1960-1982. Whereas the total child (1-14 y) death rate has fallen from 159 per 100000 (in 1960) to 86 (in 1982), road traffic deaths have risen from 8.3 11.7 (1-4 year olds) and have remained static (8.3-8.9) for 5-14 year old children. Drowning in older children has been reduced, but drownings among toddlers are still high (9.2 in 1960; 11.7 in 1982). The causes of secular trends, and factors which are known to influence these, are discussed. PMID- 4038223 TI - Auditory brainstem evoked response as a hearing test in infants and children: a follow up study. AB - In recent years the auditory brainstem evoked response (BSER) has become an established aid in assessing hearing in unco-operative subjects. We have reviewed our experience with this technique in 293 infants and children aged less than 11 years. We have found that the threshold for click BSER correlates well with the average audiometric threshold in the 2-4 kHz range. We have had encouraging preliminary experience to support the claim by other workers that 500 Hz stimuli may be used to assess low tone auditory function. In interpreting results it is important to appreciate that hearing levels may fluctuate with disorders such as otitis media and occasionally in cases of meningitis. Caution is also advised in interpreting results in cases where central nervous system pathology capable of affecting auditory pathways is known to exist. PMID- 4038224 TI - The assessment of children with school problems: evaluation of a hospital-based multidisciplinary clinic. AB - A hospital based multidisciplinary clinic for the assessment of children with school problems was evaluated. Questionnaires were sent to parents and teachers of 44 children seen during the first year of operation of the clinic. The majority of parents found the assessment and report valuable in answering their questions about the child; felt the report was clear and helpful, and the recommendations appropriate and practical. Ninety per cent of recommendations made were implemented. These results indicate that such clinics would seem to be an appropriate way to address the needs of children with school problems, an important segment of the new paediatric morbidity. PMID- 4038225 TI - Pre slaughter handling of cattle: the availability of water during the lairage period. AB - A comparison was made of the effect of providing or denying water to steers during the last 20 h before slaughter on carcase weight, bruising, muscle pH, and during the dressing process on the numbers of rumens from which ingesta was split and the number of heads and tongues condemned because of contamination with ingesta. All cattle were offered water from arrival at the abattoir until the start of the treatment period. In one experiment the steers were rested for 24 or 48 h after a 120 km journey before being slaughtered, while in a second experiment they rested for 66 h after a 725 km journey. Giving steers access to water until they were slaughtered did not affect adversely carcase weight, bruise score, muscle pH or the incidence of ingesta spillage from rumens. The number of condemned heads and tongues was not consistently related to the availability of water. In the absence of any adverse effects it is recommended that cattle be provided with water during the lairage period. PMID- 4038226 TI - Bacterial penetration of the recently oviposited shell of hens' eggs. PMID- 4038227 TI - Complications in field diagnosis of Johne's disease in sheep. PMID- 4038228 TI - A prolonged summer anthelmintic treatment for prevention of growth reduction due to abomasal nematode parasitism in young beef cattle. PMID- 4038229 TI - Sale and processing of wool affected with dermatophilosis. PMID- 4038230 TI - Coronary circulation of the healthy man exposed to tilt tests, LBNP, and head down tilt. AB - The effect of tilt (head-up and head-down) tests, LBNP tests, and 7-d head-down tilt (at -15 degrees) on coronary circulation was investigated in healthy male volunteers. Catheters were implanted into the coronary sinus and brachial artery. The Ganz catheter in the coronary sinus was used to measure volume flow in the area (constant thermodilution), pressure, and to withdraw samples of outflowing blood for biochemical analysis (acid-base equilibrium and oxygenation). Transfer from supine to upright body position, lower body negative pressure (-30 mm Hg for 20 min), as well as 15 degrees head-down (by day 5-6) produced similar changes in the basic parameters of coronary circulation-reduction of blood flow and oxygen consumption, decrease of pressure in the coronary sinus, and increase of coronary resistance. Transfer from head-up to head-down position caused opposite changes of the above parameters. The changes in coronary circulation were adequate for myocardial metabolic requirements since the biochemical composition of the outflowing blood remained essentially constant during the gravitational exposures described. PMID- 4038231 TI - Comparative study of physical and mental incapacities among Portuguese airline pilots under and over age 60. AB - This study evaluated the number of definitive flight incapacitations and deaths which occurred among Portuguese airline pilots between 1945 and 1983. Also, all pilots over 60, no longer flying, continued to be submitted to the same medical, psychological and psychomotor tests as before. The number of incapacities and deaths was related to the number of pilots by age groups of 5 years from age 20 24 to 65-69, in a total of 1528 pilots at risk. Under age 60, the pilots' careers were interrupted for pathological reasons (8) and deaths (13), mainly through unforeseen severe diseases (13) and violent deaths (6). Over age 60, no deaths occurred and the majority of the psycho-physiological problems susceptible to being considered incapacitating (10) were expressed by expected degenerative disorders which were strictly connected with aging. The rate of incapacities became higher than under age 60, but 64% of over 60 examinees were absolutely fit for flight duties. PMID- 4038232 TI - Voluntary dehydration and electrolyte losses during prolonged exercise in the heat. AB - The effects of water temperature (6 degrees, 22 degrees, 46 degrees C) and chlorination on voluntary dehydration (D), sweat electrolyte losses (SEL), and total body electrolyte losses (BEL) were studied in 12 healthy males during 6 h of intermittent treadmill exercise (1.34 m X s-1, 5% grade) in a climatic chamber (40.6 degrees C DB, 25.5 degrees C WB). Body weight (BW), rectal temperature (Tre), mean weighted skin temperature (Tsk), heart rate (HR), plasma osmolality (PO), sweat rate (SR), sweat sodium (Na+), chloride (Cl-), potassium (K+), and magnesium (MG++), urine volume, Na+, and K+ were measured. No differences were found between chlorinated and non-chlorinated treatments except SEL of Mg++. Subjects (Ss) who drank 46 degrees C (-2.1% BW) consumed approximately 50% less water (p less than 0.001), and had D which was 1.050 kg larger (p less than 0.001) than subjects who consumed 6 degrees C (-0.5 %BW). There were no significant between-group PO differences, but Tre and Tsk differed between 46 degrees and 6 degrees C (p less than 0.01), and the HR of 22 degrees and 46 degrees C were both different from 6 degrees C (p less than 0.05). SR of all groups were essentially equal, although differences in total sweat Na+ (p less than 0.02) and Cl- (p less than 0.04) losses were observed between 46 degrees and 6 degrees C. SEL of sweat K+ and Mg++ were not affected by the experimental design. Based on 24 h projections of BEL, it was concluded that K+ depletion is more likely than Na+ depletion because food is often supplemented with sodium chloride.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4038233 TI - Blink reflex as a parameter of human operator's functional state. AB - Eyelid movements (EM)--blinking frequency and duration of closed eyes--may serve as a parameter of fatigue in humans performing as operators. Twenty subjects were told to locate and follow visual signals appearing on a screen at the frequency of 4-5 X h-1 and moving in a background of bright noises. EM was recorded in infra-red rays with tiny sensors attached to glasses' rim. EEG and ECG were recorded simultaneously. It was found that a change in EM is a sensitive parameter of fatigue and better corresponds to decreased quality of performance (time of locating signal and error in following), than changes in R-R interval. In the second experimental series, symptoms of fatigue discovered by EM were accompanied by sound signals, which improved operator's performance by 15-20%. Recording of EM may be used to monitor operator's state in humans and to forecast reliability of performance. PMID- 4038234 TI - Lower body negative pressure in the tranquilized rat. AB - The application of lower body negative pressure (LBNP) to tranquilized rats was assessed as an experimental technique to evaluate the response of the cardiovascular system to hypotension. After pilot studies had demonstrated that diazepam (600 micrograms X kg-1, i.v.) had no significant influence on the pressor response to unilateral carotid occlusion in unanesthetized and unrestrained rats, subsequent rats were tranquilized. When LBNP was applied, the decline in central venous pressure was linearly related to the level of negative pressure as was the initial fall in mean arterial pressure (MAP). Pulse-interval was highly correlated with the initial fall of MAP. The results indicate that the application of LBNP in the tranquilized rat can effectively produce systemic hypotension and elicit cardiovascular reflexes similar to those reported for other animals in response to LBNP, including humans. PMID- 4038235 TI - Early central venous pressure changes in the rat during two different levels of head-down suspension. AB - The head-down suspension (i.e. antiorthostatic hypokinesia) rat is used to simulate the circulatory effects of weightlessness. However, little is known about the early cardiovascular adaptive response to simulated weightlessness and the effects of varying degrees of head-down suspension. Therefore, the purpose of this study was to characterize the early central venous pressure changes to two different levels of head-down suspension in the rat. Unanesthetized, unrestrained, female Sprague-Dawley rats (wt: 298 +/- 18 gms, mean +/- S.D.) with chronically implanted central venous pressure catheters were subjected to either a 45 degrees C head-down tilt angle (Group A, N = 8) or a 20 degrees head-down tilt angle (Group B, N = 8) using the tail-traction technique of head-down suspension. Central venous pressure increased significantly (p less than 0.05) in both groups of rats during head-down suspension with the absolute pressure level significantly (p less than 0.05) higher in Group A rats compared to Group B rats during the first 8 h of the study. At 24 h, the rats in Group B appeared to adapt earlier to head-down suspension because central venous pressure decreased to the previous baseline level whereas it remained increased in Group A rats. We conclude that the level of head-down suspension significantly affects the early central venous pressure response and subsequent cardiovascular adaption to simulated weightlessness in rats. PMID- 4038236 TI - Maxillary sinus barotrauma--case report and review. AB - A case is presented in which a mucous retention cyst that obliterated the right maxillary sinus caused symptoms due to pressure on two separate branches of the second branch of the fifth cranial nerve during a chamber dive to 112 feet. The symptoms of pain and numbness occurred at different times during and after the dive. Referred pain to the maxillary teeth was due to pressure on the posterior superior alveolar branch and paresthesia with numbness and tingling of the lip and cheek was caused from pressure on the infraorbital nerve prior to its emergence through the infraorbital foramen. The symptoms resolved promptly on recompression treatment. The underlying mechanisms for the production of sinus barotrauma and the causes of tooth and sinus pain are differentiated, and a differential diagnosis of maxillary sinus opacities is schematized. PMID- 4038237 TI - Modification of Otis-McKerrow valve for measurement of respiratory water loss. AB - An apparatus is described that allows a continuous measurement of inspired and expired gas dew-point temperature for the calculation of water loss (Eres) during ventilation. A rapid response dew-point temperature measurement method is described which is based on a small Peltier module. The compact structure with near zero system dead space minimizes potential errors inherent in many techniques used to measure Eres. The simple design and rugged construction permit the incorporation of the apparatus into many manual or personal computer controlled oxygen consumption systems. Collection of data may be done in a variety of ambient temperatures, altitudes, and activity levels. There is also the potential for creating a portable system for field use. PMID- 4038238 TI - Operational G-induced loss of consciousness: something old; something new. AB - Loss of consciousness (LOC) during exposure to +Gz occurs in aircrew flying high performance aircraft. This phenomenon is responsible for several USAF aircraft losses with accompanying loss of life. It has been recognized as a potential flying problem since 1938. Acceleration-induced LOC results in 15-to 20-s periods of aircrew total incapacitation, amnesia, and clonic spasms. It can occur at relatively low G levels and without symptoms of loss of light (blackout). Operational anti-G equipment and methods are not completely effective in preventing LOC. Considering the present status of G protection, a deficiency in the anti-G straining maneuver is considered to be the primary cause of G-induced LOC. This deficiency usually can be corrected with proper centrifuge training. Our present understanding of G protection suggests that the elimination of LOC as a serious problem for USAF high-performance aircraft operations must include the supination of aircrew to a minimum seat back angle of 60 degrees to 65 degrees. PMID- 4038239 TI - Associations between some polymorphic markers and variation in IQ and its components in Otmoor villagers. PMID- 4038240 TI - Segregation analysis of human hand preference. PMID- 4038241 TI - Familial resemblance for general cognitive ability in the Hawaii Family Study of Cognition. PMID- 4038242 TI - A systems model of health behavior change. AB - The modeling in this paper is at the level of the individual, in relation to the subsystem of health behavior. It integrates social, environmental, psychological, and physiological factors to describe the health behavior change process. It is not intended to be quantitatively predictive of behavior change, since further development of this model is needed to determine the mathematical form of the relationships between variables. The model is innovative in several ways. First, it includes health-related variables and a rich feedback structure. In contrast, attitude behavior change models often cannot explain health behavior adequately, because they do not incorporate physiological variables. Second, the model can be easily used by educators to help identify important variables for developing health education curricula. Consequently, program developers are helped in determining program intents, teaching strategies, and learning activities, and evaluative strategies which are congruent with the attitude behavior change process. PMID- 4038243 TI - Cognitive behavior therapy in the treatment of multiple personality. PMID- 4038244 TI - Social perception, social performance, and self-perception. A study with psychiatric and nonpsychiatric groups. PMID- 4038245 TI - Three methods of memory training for severely amnesic patients. PMID- 4038246 TI - On the modification of acceptability ratings for alternative child treatments. PMID- 4038247 TI - Studies on the energy reserve of Fasciola gigantica from Nigerian Zebu cattle. AB - As energy reserves in the body tissue of mature liver flukes var. Fasciola gigantica from the bile ducts of Nigerian Zebu cattle the following percentages were found: protein 60.29, lipid 11.92, carbohydrate 7.0. The analysis of the lipid fractions showed the following composition: 47% phospholipids (63% phosphatidyl choline, 28% phosphatidyl serine, 9% lysophosphatidyl choline) and 22% triglycerides, 16% fatty acids, 6% cholesterol, 5% monoacyl glycerol, and 4% cholesterol ester. PMID- 4038248 TI - [Antler amputation in Cervidae from the viewpoint of ethology and animal protection]. PMID- 4038249 TI - [Concentration and size distribution of air-borne dust particles in horse stables]. PMID- 4038250 TI - Electrophoretic analysis of proteins from night-blind mutants of Phycomyces. AB - Using two-dimensional gel electrophoresis, we have analyzed proteins from a plasma membrane-enriched fraction from Phycomyces sporangiophores. Specifically, we have compared gels for night-blind mutants and a wild-type strain to find proteins involved in the early steps of the sensory transduction chain for phototropism. In the gels for a mutant affected in the gene madA, a protein spot [51 kilodaltons (kdal) and pI 6.35] appears that is absent from the wild-type and the other mad mutants. Mutants affect in either of two madB alleles lack a protein spot (57 kdal and pI 6.6) that is present in the wild-type and all other mad strains; this spot probably represents the madB gene product. In some madC mutants, two spots (59 kdal, pI 6.5, with a covalently linked flavin; and 50 kdal, pI 6.4) are absent; however, in other madC strains, one or both of these spots are present. These four protein spots that are altered in madA, madB, and madC mutants may represent component of the photoreceptor complex responsible for phototropism in Phycomyces. PMID- 4038251 TI - Genetics, subcellular localization, and molecular characterization of 6 phosphogluconate dehydrogenase isozymes in tomato. AB - Three independent genes are responsible for 6-phosphogluconate dehydrogenase (6PGDH) activity in tomato. 6Pgdh-2, located on chromosome 12, codes for subunits of an active dimer which is restricted to the plastids. 6Pgdh-1, chromosome 4, and 6Pgdh-3, chromosome 5, code for subunits which form three dimers--two homodimers and an intergenic heterodimer. The latter three isozymes are found in the cytosol. 6Pgdh-1, 6Pgdh-2, and 6Pgdh-3 code for subunits with estimated molecular weights of 49,500, 50,500, and 51,200, respectively. The intergenic heterodimer encoded by 6Pgdh-1 and 6Pgdh-3 is thus composed of subunits that differ in length by approximately 15 amino acid residues. Divergence in the length and primary subunit structure may account for the lower thermal stability of the intergenic heterodimer compared with the corresponding homodimers. A limited survey of other solanaceous plant species suggests that the duplication of cytosolic 6PGDH-coding genes found in tomato may be widespread in the family. PMID- 4038252 TI - Experimentally induced defects of mitochondrial metabolism in rat skeletal muscle. Biological effects of the mitochondrial uncoupling agent 2,4 dinitrophenol. AB - Infusion of dinitrophenol intra-arterially into rat hind limb caused an irreversible failure of isometric twitch tension and the induction of a severe progressive contracture. Metabolite analysis of muscle in which the twitch response had grossly fatigued revealed low levels of ATP and phosphocreatine together with lactate accumulation. Studies using 31P-n.m.r. confirmed the decrease in ATP and creatine phosphate concentrations and indicated a fall in intracellular pH. It is concluded that dinitrophenol-induced myopathy does not represent a good model for the human mitochondrial myopathic condition as has been previously suggested. PMID- 4038253 TI - Phosphorylation status of liver by 31P-n.m.r. spectroscopy, and its implications for metabolic control. A comparison of 31P-n.m.r. spectroscopy (in vivo and in vitro) with chemical and enzymic determinations of ATP, ADP and Pi. AB - An investigation into the measurement of Pi and ADP in rat liver in vivo and in freeze-clamped extracts by 31P-n.m.r. spectroscopy was carried out. The concentration of Pi estimated in vivo is less than 25% [1 mM (mumol/ml of cell water)] of the value obtained from freeze-clamped liver (4 mM), whereas ADP in vivo is undetectable (1.4 mM in vitro). At 5 min after infusion of 750 mg of fructose/kg, the Pi content of liver extracts fell to 1.3 mM, whereas Pi is undetectable in vivo under these conditions [Griffiths, Stevens, Gadian, Iles & Porteous (1980) Biochem. Soc. Trans. 8, 641]. The results indicate that the lower Pi and ADP concentrations found in vivo may be due to compartmentation or binding rather than to degradation of labile organic phosphates during extraction. The results are discussed with reference to previous measurements of liver phosphates and investigations of compartmentation in the liver, as are some of the possible consequences for metabolic control in the liver of low ADP and Pi concentrations. PMID- 4038254 TI - Deuteroporphyrin-albumin binding equilibrium. The effects of porphyrin self aggregation studied for the human and the bovine proteins. AB - The binding equilibrium of deuteroporphyrin IX to human serum albumin and to bovine serum albumin was studied, by monitoring protein-induced changes in the porphyrin fluorescence and taking into consideration the self-aggregation of the porphyrin. To have control over the latter, the range of porphyrin concentrations was chosen to maker dimers (non-covalent) the dominant aggregate. Each protein was found to have one high-affinity site for deuteroporphyrin IX monomers, the magnitudes of the equilibrium binding constants (25 degrees C, neutral pH, phosphate-buffered saline) being 4.5 (+/- 1.5) X 10(7) M-1 and 1.7 (+/- 0.2) X 10(6) M-1 for human serum albumin and for bovine serum albumin respectively. Deuteroporphyrin IX dimers were found to bind directly to the protein, each protein binding one dimer, with high affinity. Two models are proposed for the protein-binding of porphyrin monomers and dimers in a porphyrin system having both species: a competitive model, where each protein molecule has only one binding site, which can be occupied by either a monomer or a dimer; a non competitive model, where each protein molecule has two binding sites, one for monomers and one for dimers. On testing the fit of the data to the models, an argument can be made to favour the non-competitive model, the equilibrium binding constants of the dimers, for the non-competitive model (25 degrees C, neutral pH, phosphate-buffered saline), being: 8.0 (+/- 1.8) X 10(8) M-1 and 1.2 (+/- 0.6) X 10(7) M-1 for human serum albumin and bovine serum albumin respectively. PMID- 4038256 TI - Iodinated fibroblast beta-glucuronidase as a ligand for receptor-mediated endocytosis. AB - Antibodies raised to human placental beta-glucuronidase were shown to cross-react with the beta-glucuronidase secreted by mouse 3T3 fibroblasts, but did not react with other lysosomal enzymes. The beta-glucuronidase secreted by 3T3 cells was purified 15000-fold by chromatography on an affinity column made from this antibody and resolved into a single component, of Mr 68000, by sodium dodecyl sulphate/polyacrylamide-gel electrophoresis. Iodinated samples of purified enzyme were taken up into mouse peritoneal macrophages by receptor-mediated endocytosis at a rate similar to that calculated previously for unlabelled enzyme, and uptake was competitively inhibited by yeast mannan. Binding of beta-glucuronidase to macrophages was saturable, with a Kd of 7 X 10(-9)l/mol, an affinity comparable with that calculated for the binding of mannosylated bovine serum albumin (Kd 1.3 X 10(-9)l/mol), a ligand specific for mannose receptors. Four times as many molecules of mannosylated albumin (12000) as of beta-glucuronidase (3000), however, bound to each cell. This purification and iodination procedure did not therefore have any adverse effect on the uptake properties of secreted beta glucuronidase, and provides a ligand with which to investigate binding and specific endocytosis into a range of different types of cell. PMID- 4038255 TI - The apparent Km of ammonia for carbamoyl phosphate synthetase (ammonia) in situ. AB - Experiments with carbamoyl phosphate synthetase (ammonia) in solution and in isolated mitochondria are reported which show the following. NH3 rather than NH4+ is the substrate of the enzyme. The apparent Km of NH3 for the purified enzyme is about 38 microM. The apparent Km for NH3 measured in intact isolated mitochondria is about 13 microM. This value was obtained for both coupled and uncoupled mitochondria and was unchanged when the rate of carbamoyl phosphate synthesis was increased 2-fold by incubating uncoupled mitochondria in the presence of 5 mM-N acetylglutamate. According to the literature, the concentration of NH3 in liver is well below the measured apparent Km. On the basis of this and previous work we conclude that, quantitatively, changes in liver [NH3] and [ornithine] are likely to be the most important factors in the fast regulation of synthesis of carbamoyl phosphate and urea. This conclusion is consistent with all available evidence obtained with isolated mitochondria, isolated hepatocytes, perfused liver and whole animals. PMID- 4038257 TI - Heterogeneity of high-mobility-group protein 2. Enrichment of a rapidly migrating form in testis. AB - A determination of the absolute amounts of high-mobility-group proteins 1 and 2 (HMG1 and HMG2) in rat tissues demonstrated that amounts of HMG2 were low in non proliferating tissues, somewhat higher in proliferating and lymphoid tissues, but were extremely elevated in the testis. This increase was due to a germ-cell specific form of HMG2 with increased mobility relative to somatic HMG2 on acid/urea/polyacrylamide-gel electrophoresis. To determine if the findings in the rat were a general feature of spermatogenesis, testis (germinal), spleen (lymphoid), and liver (non-proliferating) tissues from various vertebrate species were examined for their relative amounts of HMG1 and HMG2, and for HMG2 heterogeneity. Bull, chimpanzee, cynomologus monkey, dog, gopher, guinea pig, hamster, mouse, opossum, rabbit, rat, rhesus monkey, squirrel and toad (Xenopus) tissues were analysed. Nearly all species showed relatively high contents of HMG2 in testis tissue, whereas HMG1 contents were similar in all species and tissues. Ten of thirteen species showed a rapidly migrating HMG2 subtype in testis tissue, separable by acid/urea/polyacrylamide-gel electrophoresis. Xenopus, which lacks HMG2 in somatic tissues, showed an HMG2-like protein in testis tissue. Although the rapidly migrating HMG2 subtype in species other than rat was not testis specific, it was always enriched in the testis. This study indicates that increased amounts of HMG2 and the enrichment of a rapidly migrating HMG2 subtype are general features of spermatogenic cells. PMID- 4038258 TI - Role of uricase in the triggering of germination of Bacillus fastidiosus spores. AB - The likelihood that uric acid was the only compound capable of triggering germination of Bacillus fastidiosus spores was reinforced by the finding that ureidoglycollic acid, urea, NH4Cl, 2,8-dihydroxypurine and a combination of L alanine and O-carbamoyl-D-serine were ineffective as germinants. Uric acid triggered germination of B. fastidiosus was prevented by a range of inhibitors that also inhibited uricase activity in dormant spore extracts. O2 uptake during germination started immediately after addition of uric acid, possibly as a consequence of the oxidation of uric acid by the enzyme uricase. Germination showed a dependence on uric acid concentration, with a relatively high Km (4-5 mM). During the first 10 min of germination of heat-activated spores there was no detectable change in the number of spore-cortex reducing groups, indicating that selective cortex hydrolysis is not involved in the trigger mechanism of germination of B. fastidiosus. On the basis of the results, a model is proposed in which re-initiation of uricase activity is the mechanism by which B. fastidiosus spores are triggered to emerge from the dormant state. PMID- 4038259 TI - Proteins of the kidney microvillar membrane. Purification and properties of carboxypeptidase P from pig kidneys. AB - Carboxypeptidase P has been purified by immunoaffinity chromatography from pig kidneys. A single-step assay with Z-Pro-Met (where Z represents benzyloxycarbonyl) as substrate was used, methionine being determined by using L amino acid oxidase and horseradish peroxidase. The enzyme constitutes about 1.5% of the kidney microvillar proteins. Triton X-100-solubilized and papain-released forms of the enzyme were isolated. The former had an apparent subunit Mr of 135 000, and the latter form contained two polypeptide chains of Mr 128 000 and 95 000. The undenatured forms were dimeric proteins. In common with other microvillar hydrolases, carboxypeptidase P was a glycoprotein and each subunit contained one Zn atom. MnCl2 (1 mM) in the assay was necessary for maximum activity; in its absence, 0.5 mM-ZnSO4 produced a limited activation, but was inhibitory at higher concentrations. The Km for Z-Pro-Met, in the presence of MnCl2, was 4.1 mM, and the kcat. for freshly prepared enzyme was 1230 min-1. The enzyme lost activity during storage at -20 degrees C. In a limited survey of peptides, hydrolysis was observed only with substrates containing a proline, alanine or glycine residue in the P1 position, and these included angiotensins II and III. The best substrate in this series was Val-Ala-Ala-Phe. PMID- 4038260 TI - Post-translational assembly and glycosylation of laminin subunits in parietal endoderm-like F9 cells. AB - Non-reducing and reducing sodium dodecyl sulphate/polyacrylamide-gel electrophoresis of laminin synthesized in parietal endoderm-like F9 cells demonstrated that only AB1B2 complex goes through intracellular traffic for oligosaccharide side-chain processing and secretion. Glycosylation was not necessary for subunit assembly. Assembly was suggested to proceed through B1B2 to AB1B2. Among the pools of monomer subunits, the B2 pool was smallest. PMID- 4038261 TI - Differential binding of glycine- and taurine-conjugated bile acids to insoluble calcium phosphate. AB - It is demonstrated that bile acids bind to insoluble calcium phosphate at pH values beyond 5.5. Significant binding occurs with glycine-conjugated dihydroxy bile acids. Results indicate that these bile acids are bound in a micellar mode. Taurine conjugation almost completely inhibits the binding of these bile acids to insoluble calcium phosphate. Since glycine-conjugated dihydroxy bile acids are predominant in the rabbit, but not in the rat, our results suggest an explanation for the intriguing species-dependence of casein-induced hypercholesterolaemia, which is high in the rabbit but absent in the rat. PMID- 4038262 TI - Effects of the mode of addition of acyl-CoA on the initial rate of formation of acylcarnitine in the presence of carnitine by intact rat liver mitochondria in vitro. AB - Time courses for the formation of palmitoylcarnitine from palmitoyl-CoA and carnitine, catalysed by the overt activity of carnitine palmitoyltransferase (CPT I) in rat liver mitochondria, were obtained. Significant initial non-linearity was observed only when reactions were started by addition of a concentrated solution of palmitoyl-CoA (4mM, to give a final concentration of 100 microM) uncomplexed to albumin. Minimal effects were observed when the reactions were started by addition of palmitoyl-CoA-albumin mixtures, even though the final palmitoyl-CoA/albumin molar ratios in the assay medium were identical in the two sets of experiments. PMID- 4038263 TI - Exhaustive laccase-catalysed oxidation of a lignin model compound (vanillyl glycol) produces methanol and polymeric quinoid products. AB - Laccase-catalysed oxidation of the lignin-related phenol vanillyl glycol results in the initial formation of dimers and subsequent polymerization. The polymerization is accompanied by a liberation of methanol corresponding to 15-20% demethylation. Visible spectra together with reduction experiments suggest the simultaneous formation of o-quinones. The participation of quinone formation in the polymerization process and the possible role of such intermediates in lignin biodegradation is discussed. PMID- 4038264 TI - Rat skin calcium-binding protein is parvalbumin. AB - Only one major low-Mr calcium-binding protein could be isolated by h.p.l.c. procedures from aqueous extracts of homogenized adult rat skin. This was shown by tryptic peptide mapping and independent amino acid sequence analysis to be identical in all 109 residues with the parvalbumin from rat skeletal muscle. This calcium-binding protein was not in skin epidermis, but was confined to the dermal layer. Skin calcium-binding protein is therefore parvalbumin. PMID- 4038265 TI - Kinetic pathways of formation and dissociation of the glycerol-3-phosphate dehydrogenase-fructose-1,6-bisphosphate aldolase complex. AB - Quantitative analysis of the time courses of fluorescence anisotropy changes due to the binding of fructose-1,6-bisphosphate aldolase to the dissociable cytoplasmic glycerol-3-phosphate dehydrogenase covalently labelled with fluorescent dye was carried out. The behaviour of the aldolase-dehydrogenase system seems to be consistent with a cyclic reversible model characterized by the formation and dissociation of complexes of both the monomeric and the dimeric forms of dehydrogenase with aldolase, and rapid equilibrium between the free monomeric and dimeric forms of dehydrogenase. The half-life time of the formation of dimeric dehydrogenase-aldolase complex at the concentration of the enzymes expected to exist in the cell (i.e. in the micromolar range) is some minutes, and the time needed for equilibration between the aldolase-bound dimeric and monomeric forms of dehydrogenase is a few minutes as well. Consequently, one may expect that both the formation and the dissociation of this heterologous enzyme complex have physiological relevance. PMID- 4038266 TI - Turnover of messenger RNA, apoprotein and haem of cytochrome P-450b + e induced by phenobarbitone in rat liver. AB - A single injection of phenobarbitone elicits asynchronous behaviour in the pattern of induction of mRNA, apoprotein and haem of cytochrome P-450b + e. The mRNA content reaches a maximum around 16h, the apoprotein content reaches a maximum around 30-36h, and the holoprotein content shows biphasic behaviour, with maxima around 16h and 30-36h. With the use of CoCl2 to block fresh transcription of cytochrome P-450b + e mRNA, the half-life of the preinduced mRNA was found to be 3h. The apoprotein and haem moieties of cytochrome P-450b + e turn over with half-lives of 16h and 8h respectively. The pattern of induction of delta aminolaevulinate synthase shows biphasic behaviour, with maxima around 16h and 30 36h. The biphasic behaviour of the holoprotein content is thus due to differences in the extent of saturation of the apoprotein with haem, the process being regulated by the activity of the rate-limiting delta-aminolaevulinate synthase and the independent faster turnover rate of haem with respect to the apoprotein. Massive degradation of the haem moiety of preformed cytochrome P-450b + e results in the subsequent degradation of the apoprotein. PMID- 4038267 TI - Differential effect of anionic and cationic drugs on the synaptosome-associated acetylcholinesterase activity of dog brain. AB - The evoked effects of the negatively charged drugs phenobarbital and barbituric acid, the positively charged imipramine, perphenazine and trifluoperazine, and the neutral primidone, on the synaptosome-associated acetylcholinesterase activity were studied. A marked increase in the enzyme activity was exhibited in the presence of low concentrations (up to 3 mM) of phenobarbital, barbituric acid and primidone. Higher concentrations (up to 10 mM), however, led to a progressive inhibition of the enzyme activity. However, the activity of the enzyme was not affected by imipramine, but it was decreased by perphenazine and trifluoperazine. Arrhenius plots of acetylcholinesterase activity exhibited a break point at 23.4 degrees C for the untreated (control) synaptosomes, which was shifted to around 16 degrees C in the synaptosomes treated with the charged drugs. The allosteric inhibition by F- of acetylcholinesterase was studied in control synaptosomes and in those treated with the charged drugs. Changes in the Hill coefficients in combination with changes in Arrhenius activation energy produced by the charged drugs would be expected if it is assumed that charged drugs 'fluidize' the synaptosomal plasma membranes. PMID- 4038268 TI - Nomenclature Committee of the International Union of Biochemistry (NC-IUB). Nomenclature for incompletely specified bases in nucleic acid sequences. Recommendations 1984. PMID- 4038269 TI - Hydrogen transfer between ethanol molecules during oxidoreduction in vivo. AB - Rates of exchange catalysed by alcohol dehydrogenase were determined in vivo in order to find rate-limiting steps in ethanol metabolism. Mixtures of [1,1-2H2]- and [2,2,2-2H3]ethanol were injected in rats with bile fistulas. The concentrations in bile of ethanols having different numbers of 2H atoms were determined by g.l.c.-m.s. after the addition of [2H6]ethanol as internal standard and formation of the 3,5-dinitrobenzoates. Extensive formation of [2H4]ethanol indicated that acetaldehyde formed from [2,2,2-2H3]ethanol was reduced to ethanol and that NADH used in this reduction was partly derived from oxidation of [1,1 2H2]ethanol. The rate of acetaldehyde reduction, the degree of labelling of bound NADH and the isotope effect on ethanol oxidation were calculated by fitting models to the found concentrations of ethanols labelled with 1-42H atoms. Control experiments with only [2,2,2-2H3]ethanol showed that there was no loss of the C-2 hydrogens by exchange. The isotope effect on ethanol oxidation appeared to be about 3. Experiments with (1S)-[1-2H]- and [2,2,2-2H3]ethanol indicated that the isotope effect on acetaldehyde oxidation was much smaller. The results indicated that both the rate of reduction of acetaldehyde and the rate of association of NADH with alcohol dehydrogenase were nearly as high as or higher than the net ethanol oxidation. Thus, the rate of ethanol oxidation in vivo is determined by the rates of acetaldehyde oxidation, the rate of dissociation of NADH from alcohol dehydrogenase, and by the rate of reoxidation of cytosolic NADH. In cyanamide-treated rats, the elimination of ethanol was slow but the rates in the oxidoreduction were high, indicating more complete rate-limitation by the oxidation of acetaldehyde. PMID- 4038270 TI - Incorporation of the 1-pro-R and 1-pro-S hydrogen atoms of ethanol in the reduction of acids in the liver of intact rats and in isolated hepatocytes. AB - Ethanol oxidation causes redox effects. The coupling of this oxidation via NADH to intermediary metabolism was studied in order to reveal the underlying mechanisms. Isolated rat hepatocytes were incubated with [1,1-2H2]-, (1R)-[1-2H]- and (1S)-[1-2H]-ethanol and the 2H incorporation was measured in lactate, beta hydroxybutyrate, fumarate, malate, succinate, alpha-oxoglutarate and citrate. The results differed in the following ways from results obtained in intact rats. Lactate became labelled to an increasing extent, and in more than one position, indicating labelling of pyruvate. A small and constant fraction of malate and fumarate was formed without access to [2H]coenzyme. Addition of aspartate increased this fraction, which was concluded to be formed in the mitochondria. Citrate was essentially unlabelled. The 2H from (1R)-[1-2H]ethanol contributed to malate to a larger extent and to beta-hydroxybutyrate to a smaller extent, and 2H from (1S)-[1-2H]ethanol contributed to lactate to a smaller extent. These results indicate that the exchange via shuttle system was less efficient in isolated hepatocytes than in intact rats. The 2H incorporation was independent of concentration of [1,1-2H2]ethanol when this was above 5mM. Additions known to increase ethanol elimination, and cyanamide, which decreases it, had no marked effect on the 2H incorporation. This indicates equilibration of the NADH bound to alcohol dehydrogenase with free NADH. Disulfiram and cyanamide caused a decrease in the relative incorporation from (1S)-[1-2H]ethanol into malate in liver of intact rats. Addition of cyanamide to incubations with hepatocytes resulted in a decrease of the contribution of 2H from (1S)-[1-2H]ethanol in lactate, beta hydroxybutyrate and malate. This indicates that acetaldehyde was only oxidized in the mitochondrial compartment. PMID- 4038271 TI - Degradation of mono-oleoylglycerol, trioleoylglycerol and phosphatidylcholine in emulsions and lipoproteins by rat hepatic acylglycerol lipase. AB - The purpose of this study was to characterize the lipolytic activities released by heparin from rat livers. Heparin perfusates of rat livers degraded monooleoylglycerol, trioleoylglycerol and phosphatidylcholine in emulsions as well as in chylomicrons, chylomicron remnants, low-density lipoprotein/high density lipoprotein-1 (LDL/HDL-1) and high-density lipoprotein-2 (HDL-2). The preferred substrate was mono-oleoylglycerol. Heparin perfusates were separated by chromatography on either heparin-Sepharose or N-desulphated, N-acetylated heparin Sepharose into at least two related lipases which differed in their ability to hydrolyse HDL-2 phosphatidylcholine, but not in their ability to degrade mono oleoylglycerol, trioleoylglycerol and phosphatidylcholine in emulsions. The sodium dodecyl sulphate (SDS)/polyacrylamide-gel-electrophoretic patterns of heparin perfusates purified on either normal or N-desulphated N-acetylated heparin-Sepharose were the same, despite differences in their ability to degrade HDL-2 phosphatidylcholine. There was a single band of Mr 56000 without 2 mercaptoethanol in the SDS disruption buffer and three major bands, of Mr 62000, 59000 and 56000, with 2-mercaptoethanol present. When mono-oleoylglycerol lipase was purified 161-fold, there was a concomitant enrichment of the Mr-56000 protein. PMID- 4038272 TI - Comparison of human lactoferrins from milk and neutrophilic leucocytes. Relative molecular mass, isoelectric point, iron-binding properties and uptake by the liver. AB - Human lactoferrins isolated from neutrophilic leucocytes and milk by CM-Sephadex chromatography were similar in Mr (76000) and pI (8.7). Upon acidification, both proteins released their two Fe3+ ions/molecule in a similar biphasic way. Both proteins intravenously injected into mice were cleared from plasma at the same rate. The maximal uptakes by the liver, which occurred 5 min after injection, were inhibited to the same extent by milk lactoferrin used as a competitor. PMID- 4038273 TI - Inositol phosphate formation in fMet-Leu-Phe-stimulated human neutrophils does not require an increase in the cytosolic free Ca2+ concentration. AB - The accumulation of inositol phosphates in myo-[3H]inositol-labelled human neutrophils stimulated with the chemotactic peptide fMet-Leu-Phe was measured. The challenge with the chemotactic peptide caused the generation of inositol monophosphate (InsP), inositol bisphosphate (InsP2) and inositol trisphosphate (InsP3). The formation of the three inositol phosphates followed a differential time course: InsP3 accumulated very rapidly and transiently, whereas InsP increased steadily for more than 2 min. Inositol phosphate formation was only partially decreased by procedures which prevented the fMet-Leu-Phe-dependent increase of cytosolic free Ca2+ concentration. PMID- 4038274 TI - Structure of heparin-derived tetrasaccharides. AB - The structure of heparin was examined by characterizing a disaccharide and five of the more than a dozen tetrasaccharide components obtained by its depolymerization with flavobacterial heparinase. Enzymic depolymerization of porcine mucosal heparin results in a mixture of di-, tetra-, hexa- and higher oligo-saccharides. The di- and tetra-saccharide components represent 75mol/100mol of these heparin fragments. Ion-exchange chromatography indicates the presence of only one disaccharide, deltaIdu2S(1----4)-alpha-D-GlcNS6S (where Idu is iduronic acid, deltaIdu is 4-deoxy-alpha-L-threo-hex-4-enopyranosyluronic acid, GlcN is glucosamine, GlcA is glucuronic acid and S is sulphate), but results in the isolation of five major and at least seven minor tetrasaccharide components. The structures of the disaccharide and five major tetrasaccharides were determined by chemical, enzymic, electrophoretic and spectroscopic methods, including 13C, 1H n.m.r. and fast atom bombardment-m.s. The structure of these five tetrasaccharides are: delta Idu2S(1----4)-alpha-D-GlcNS6S(1---4)-alpha-L-Idu2S(1- --4)-alpha -D-GlcNS6S; delta Idu2S(1----4)-alpha-D-GlcNS6S(1----4)-beta-D-GlcA(1 -- -4)- alpha-D-GlcNS6S; delta Idu2S(1----4)-alpha-D-GlcNS(1----4)-beta-D-GlcA delta Idu2S(1----4)-alpha-D-GlcNAc(1----4)-beta-D-GlcA(1----4)- alpha-D-GlcNS6S; and delta Idu2S(1----4)-alpha- D-GlcNAc(1----4)-alpha-L-Idu(1----4)-alpha-D GlcNS6S. Biological activity for the disaccharide and the five major tetrasaccharides was examined, and none of them were found to possess significant anticoagulant activity. PMID- 4038275 TI - Protection of rats by clofibrate against the hypoglycaemic and toxic effects of hypoglycin and pent-4-enoate. An ultrastructural and biochemical study. AB - An ultrastructural and biochemical study of the toxic and hypoglycaemic effects of hypoglycin and pent-4-enoate was made on the livers of normal and clofibrate fed rats. Injection of hypoglycin to rats doubles (from 22% to 44%) the volume fraction of mitochondria and decreases (from 1.05% to 0.26%) the volume fraction of peroxisomes in hepatocytes. The fast-acting toxin pent-4-enoate causes few ultrastructural changes except for the accumulation of lipids. In male adult rats fed with 0.5% clofibrate in their diet for 1-2 months, the volume fraction occupied by peroxisomes and mitochondria in hepatocytes rose to 6.26% and 29.5% respectively. Clofibrate feeding apparently protected the animals against the toxic, hypoglycaemic and hypothermic effects of hypoglycin and of pent-4-enoate, and completely prevented the ultrastructural damage caused by hypoglycin. After hypoglycin administration, hepatic mitochondrial butyryl-CoA dehydrogenase activity was inhibited by more than 90% and, surprisingly, the activity of the peroxisomal enzymes studied was largely preserved. When hypoglycin was given to rats fed on a clofibrate-containing diet, the oxidation of decanoylcarnitine, which was incomplete after hypoglycin treatment alone, remained incomplete with uncoupled mitochondria, but became apparently complete with coupled mitochondria. In the latter condition, there was a slowing of the rate during the last quarter of the pulse of oxygen uptake. Further, butyryl-CoA dehydrogenase activity was much less affected by hypoglycin in clofibrate-fed animals. Pent-4-enoate does not inhibit beta-oxidation in coupled mitochondria from clofibrate-treated rats. PMID- 4038276 TI - Urinary excretion of isomers of biliverdin after destruction in vivo of haemoproteins and haemin. AB - The amount and isomeric composition of urinary biliverdin in rabbits were analysed by h.p.l.c. Physiological values were maintained after the injection of haemin. On the other hand, when haemoglobins from several mammalian species were injected into rabbits, the excretion of biliverdin-IX alpha and biliverdin-IX beta were increased 6-18-fold and 32-66-fold respectively over physiological excretion. Injection of myoglobin resulted in a 44-fold increase in excretion of the IX alpha-isomer. Coupled oxidation with ascorbate of haemoglobin and myoglobin by oxygen produced mainly the IX alpha- and IX beta-isomers from haemoglobin and the IX alpha-isomer from myoglobin. The destruction of part of the haem from injected haemoproteins by non-enzymic chemical degradation would account for the observed respective increases in the excretion of biliverdin isomers. The excretion of biliverdin isomers after the injection of phenylhydrazine into rabbits was similar to that after the injection of haemoglobin. PMID- 4038277 TI - Structure of covalent insulin-receptor complexes (I-S-S-R) in isolated rat adipocytes and human placental membranes. AB - The structure of naturally-formed covalent disulphide-linked complexes between insulin and its receptor was examined by sodium dodecyl sulphate/polyacrylamide gel electrophoresis. To prevent destabilization of disulphide bonds at alkaline pH the standard discontinuous electrophoresis conditions were changed to a continuous buffer system at pH 7.0. 125I-insulin was first bound to either rat adipocytes or human placental membranes for 10 min at 37 degrees C. After washing, non-dissociable radioactivity was extracted from cells or membranes in Triton X-100 and immunoprecipitated with an antiserum (B-2) to the insulin receptor. Electrophoresis of the immune precipitate revealed the two smaller of the three reported species of native insulin receptor (Mr values approx. 350 000, 290 000 and 260 000); in addition, a species of Mr 200 000 was also frequently observed in adipocytes. When non-dissociable 125I-insulin was chemically crosslinked to adipocytes or placental membranes, prior to solubilization and immunoprecipitation, all three species of the native receptor were labelled; after reduction, only a single species of Mr 130000 was observed. These findings indicate that disulphide exchange of insulin occurs with the Mr 130000 (alpha) binding subunit within partially reduced species of the native, oligomeric receptor. The degree of disulphide binding of insulin could therefore depend on the relative abundance of partially reduced receptor species and on the redox state of the cell membrane. PMID- 4038278 TI - Alterations in fucosyl oligosaccharides of glycoproteins during rat liver regeneration. AB - [3H]Fucose-labelled glycopeptides in the slices of liver 24h after partial hepatectomy were fractionated on Sephadex G-50. Glycopeptides from regenerating liver contained a higher proportion of lower-Mr components than did controls. Regenerating liver contained a higher proportion of glycopeptides that were bound to concanavalin A-Sepharose and were subsequently eluted with 20mM-methyl alpha-D glucopyranoside than did controls. Concanavalin A-bound glycopeptides from each source were entirely bound to a lentil lectin-Sepharose column. Both the concanavalin A-bound and -unbound fractions from regenerating liver were indistinguishable from the respective controls by Bio-Gel P6 column chromatography and neuraminidase digestion. These results show that fucosyl glycopeptides from regenerating liver contain a higher proportion of biantennary species with core fucose residues than do controls. Glycopeptides from regenerating livers 12h, 72h and 144h after partial hepatectomy were also examined; however, the difference was not significant. These observations suggest that the alterations in fucosyl glycopeptides may be related to rapid growth of hepatocytes 24h after partial hepatectomy. No significant difference was found in either [3H]mannose- or [3H]fucose-labelled glycoproteins from regenerating liver and from controls by sodium dodecyl sulphate/polyacrylamide-gel electrophoresis, suggesting that the alteration in glycopeptides should depend on some differences in the late stage of oligosaccharide processing. PMID- 4038282 TI - FEBS advanced course. Mathematical modeling of cellular processes. October 29 November 2, 1984. PMID- 4038280 TI - Metabolism of glycine- and hydroxyproline-containing peptides by the isolated perfused rat kidney. AB - Isolated perfused rat kidneys removed considerable quantities of glycyltyrosine, glycylhydroxyproline, tetraglycine and prolylhydroxyproline from the perfusate. The component amino acids are released into the perfusate and, in the case of the glycine-containing peptides, there is increased synthesis of serine. Removal of peptides was more than could be accounted for on the basis of filtration, so antiluminal metabolism is indicated. Metabolism of such peptides by the kidney may contribute to renal serine synthesis in vivo. PMID- 4038279 TI - Transcytosis and paracellular movements of horseradish peroxidase across liver parenchymal tissue from blood to bile. Effects of alpha-naphthylisothiocyanate and colchicine. AB - The pathways for the entry of horseradish peroxidase (HRP) into bile have been investigated using the isolated perfused rat liver operating under one-pass conditions. Following a 1 min one-pass infusion of HRP, two peaks of HRP activity were noted in the bile. The first, at 5-7 min post-infusion, correlated with the biliary secretion of the [3H]methoxyinulin which was infused simultaneously with the HRP. The second peak of HRP activity occurred at 20-25 min, and correlated with the biliary secretion of 125I-IgA, which was also infused simultaneously with the HRP. If the isolated livers were perfused with a medium containing 2.5 microM-colchicine, the biliary secretion of IgA and the second secretion peak of HRP were inhibited by 60%. If rats were pretreated for 12h with alpha naphthylisothiocyanate (25mg/100g body wt.) prior to liver isolation, the biliary secretion of [3H]methoxyinulin and the first secretion peak of HRP were increased. Taken together, these results suggest that HRP enters the bile via two routes. The faster route, which was increased by alpha-naphthylisothiocyanate and correlated with [3H]methoxyinulin entry into bile, was probably paracellular, involving diffusion across tight junctions. The slower route, which was inhibited by colchicine and correlated with the secretion of IgA, was probably due to transcytosis, possibly within IgA and other transport vesicles. PMID- 4038281 TI - Kinetics of enzymes requiring long-chain acyl-CoA esters as substrates: effects of substrate binding to albumin. PMID- 4038283 TI - Thermodynamics of self-organization and evolution. PMID- 4038284 TI - Mathematics of organizationally complex systems. AB - Our approach to the development of an appropriate formalism for organizationally complex systems has been to search for a general formalism that would retain the essential nonlinear features (at least in approximate form) and yet would be amenable to mathematical analysis. The power-law formalism, described in detail elsewhere, leads naturally to a system of nonlinear differential equations, which is called an "S-system" because it captures the saturable and synergistic properties intrinsic to biological and other organizationally complex systems. Some of the advantages of this formalism and its implications for complex systems are discussed. Although the power-law formalism was originally developed as an "approximation", there are now several examples of "exact" representation by S systems. In fact, a wide range of nonlinear equations can be recast in the form of S-systems. Such recasting and the use of algorithms optimized for S-systems greatly improves the efficiency of solution over that obtainable with conventional algorithms. PMID- 4038285 TI - On optimum properties in the design of metabolic and epigenetic systems. AB - The actual potential of a metabolic system is determined by its enzyme "spectrum", i.e. the amount of the various enzymes present. The paper addresses the problem whether this spectrum can be designed in accordance with a general principle. The long prehistory of selection of any real metabolic system suggests the optimal adaptation to a given set of selection criteria as a possible design principle. It is shown that not every (bio)chemical reactor automatically displays an optimal construction in this sense, but metabolic systems are structured such that they can do so. Structural features that lead to optimizable dynamics include: kinetic autocatalysis, stoichiometric autocatalysis, competition for the allocation of biosynthetic capacity, required economy in external resources of the system, and competition of systems for common nutrients or other resources. In these circumstances the enzyme spectrum has a distinct optimum that can be approached by stepwise adaptation and selection. PMID- 4038286 TI - Compartmental analysis: theoretical aspects and application. AB - The basic equations governing the kinetics of metabolic compartmental systems are presented. The most difficult problem in compartmental analysis is the so-called inverse problem which is the estimation of model parameters from experimental data. Two examples are considered how to tackle this problem. The first example concerns the distribution of isotopic carbon atoms in the citric acid cycle. Starting from a matrix formulation of the problem the major steps are outlined towards an analytical solution for this rather complex system. An application of the theoretical approach to the citric acid cycle of rabbit reticulocytes is given. The second problem deals with the kinetic characterization of biochemical reactions proceeding at the same time in different physiological spaces with different rates. Such a situation is, for example, the infection of red blood cells by malaria parasites. Both the host cell and the parasite possess the complete glycolytic pathway. A theoretical approach is proposed to estimate the flux rates through this pathway separately for each of the two spaces when only the total rates and metabolite concentrations are available as experimental data. PMID- 4038287 TI - A theory of alternative designs for biochemical control systems. AB - Any theory of alternative designs must include (a) an appropriate language for describing alternatives, (b) methods of analysis for relating system behavior to changes in design elements, and (c) methods for critically comparing the behavior of alternatives. Over the past two decades we have been reasonably successful in developing a theory of alternative designs that meets these basic requirements. The language for describing alternatives is provided by the S-system of differential equations discussed elsewhere in this volume. The methods of analysis consist of adaptations of conventional methods from control theory and newly developed algorithms specific for S-systems. The methods for making critical comparisons perhaps are less familiar and will be treated in some detail. Several applications of this theory to alternative designs for biochemical control are reviewed. PMID- 4038288 TI - Application of control analysis in studies of regulation of intermediary metabolism. PMID- 4038289 TI - Stochastic theory of evolution of biochemical networks. PMID- 4038290 TI - Efficiency and design of simple metabolic systems. AB - A theoretical approach to the explanation of the structural design of metabolic pathways is presented. It is based on the hypothesis that due to natural selection during evolution the cellular metabolism of present-day organisms may be characterized by optimal properties. Two cardinal terms enter the theory: 1) the efficiency of metabolic pathways and 2) the evolutionary effort for the change of the kinetic parameters of the involved enzymes by mutations of the corresponding genes. For both quantities simple mathematical expressions are proposed. By maximizing the efficiency under the constraint of a constant evolutionary effort the theory allows the calculation of the optimal parameter distribution. The theoretical concept is applied to simple metabolic systems consisting of monomolecular reactions only. It is shown that in the optimal state of the linear enzymatic chain the evolutionary effort is mainly spent on the enzymes located at the beginning of the chain. This tendency is more pronounced if the kinetic equations of the enzymes are first-order rate laws. With respect to Michaelis-Menten enzymes the optimal state is characterized by a decrease of the maximal activities and an increase of the fractional saturation of the enzymes towards the end of the chain. PMID- 4038291 TI - Membrane stability and dynamics of cell shape. PMID- 4038292 TI - Bilayer couple as a possible mechanism of biological shape formation. PMID- 4038293 TI - Problems in the development of pattern with special reference to positional information in limb morphogenesis. PMID- 4038294 TI - Mathematical modeling of immobilized enzyme systems. AB - We model the interaction of reaction and diffusion in immobilized enzyme systems by P.D.E.s or simpler equations. We present models with only one steady state, others with multiple steady states (in particular one related to morphogenesis) and some with periodic solutions. The usefulness of continuation methods to resolve this complexity of behaviors is pointed out. PMID- 4038295 TI - A novel oxidation of the carcinogen N-hydroxy-N-2-fluorenylacetamide catalyzed by peroxidase/H2O2/Br-. AB - N-Hydroxy-N-2-fluorenylacetamide, a proximate carcinogenic metabolite of N-2 fluorenylacetamide, is oxidized largely to 2-nitrosofluorene by lactoperoxidase or extract of peroxidative activity of rat uterus in an H2O2- and Br- -dependent reaction. Evidence is presented that the oxidizing species includes OBr- (HOBr). This novel oxidation may be involved in carcinogenesis by N-arylhydroxamic acids. PMID- 4038296 TI - A clover mutant lacking the chlorophyll a- and b-containing protein antenna complexes. AB - A chlorophyll deficient mutant of clover has been examined by SDS-PAGE, spectrophotometric and electron microscopic methods. By a comparison of the absorption and first derivative spectra of acetone extracts from the mutant and normal biotypes, we observed a deficiency in chlorophyll b for the mutant biotype. The calculated chlorophyll a/b ratios, using the method of Arnon (Plant Physiol. 24, 1-15, 1949), approached infinity for the mutant whereas it ranged from 3.0-3.3 in the wild-type. The low temperature (77 degrees K) fluorescence emission bands in the 685-695 nm region could not be differentiated for the biotypes; however, the long wavelength emission band (near 740 nm in the wild type) was shifted to shorter wavelengths (ca 720-725 nm) in the mutant indicating loss of photosystem I antenna. The SDS-PAGE profile of the mutant biotype showed a dramatic decline in the Coomassie stained polypeptides of apparent molecular weights similar to those of LHC II. Transmission electron micrographs of the mutant and normal tissue exhibited similar extents of grana-stacking, indicating that a component(s) other than the LHC II may be responsible for membrane adhesion in this mutant. PMID- 4038297 TI - A further assessment of the sub-nucleosomal product, "peak A", from Physarum polycephalum. AB - Nuclease digestion studies of Physarum polycephalum nuclei (1-3) and nucleoli (4) over the past few years have been centred on a number of modified nucleosomal products which have been related to active-gene regions of the genome. We have re investigated one such particle, peak A, using the techniques of differential melting and polyacrylamide gel electrophoresis and show that this material is unlikely to be a specific histone:DNA complex as suggested by earlier authors. PMID- 4038298 TI - In vivo metabolism of topically applied retinol and all-trans retinoic acid by the rabbit cornea. AB - Corneas of normal and vitamin A-deficient rabbits were treated topically with [11, 12-3H] retinol or [11, 12-3H] all-trans retinoic acid. Methanol extracts of these corneas were analyzed by high pressure liquid chromatography. Radiolabeled compounds were extracted from the corneas which co-migrated chromatographically with known retinoid standards. In agreement with studies on other tissues and organs, retinol was metabolized to retinoic acid and more polar compounds by corneas of normal and vitamin A-deficient rabbits. All-trans retinoic acid was isomerized to 13-cis retinoic acid in normal rabbit corneas; however, this trans cis isomerization did not occur in vitamin A-deficient, xerophthalmic corneas. PMID- 4038299 TI - Tetrameric alkaline phosphatase in human liver plasma membranes. AB - Molecular weights of native membrane-bound alkaline phosphatase released by butanol and by nonionic detergents were more than twice that of the purified dimeric enzyme. Alkaline phosphatase released by phosphatidylinositol-specific phospholipase-C was of both high and low molecular weight: the former was a protomer of a single protein of the same molecular size as monomeric alkaline phosphatase. We conclude that the membrane-bound enzyme is probably a tetramer. PMID- 4038300 TI - DNA crosslinking by 3'-(3-cyano-4-morpholinyl)-3'-deaminoadriamycin in HT-29 human colon carcinoma cells in vitro. AB - The Adriamycin analog, 3'-(3-cyano-4-morpholinyl)-3'-deaminoadriamycin, is 100- to 1000-fold more active than Adriamycin as an antitumor agent in vivo and in vitro. The interaction of 3'-(3-cyano-4-morpholinyl)-3'deaminoadriamycin and Adriamycin with DNA has been studied in HT-29 human colon carcinoma cells in vitro. The Adriamycin analog produced significant DNA-DNA crosslinking at a drug concentration range that resulted in from 1 to 4 logs of cell kill, but did not produce any DNA-protein crosslinks. Equitoxic concentrations of Adriamycin produced no significant levels of DNA-DNA crosslinks. The formation of DNA-DNA crosslinks by the Adriamycin derivative is an additional mechanism of action that may account for the high potency of this agent. PMID- 4038301 TI - Olfactory, gas chromatographic and mass-spectral analyses of fecal volatiles traced to ingested licorice and apple. AB - Volatile components of two foodstuffs with characteristic aromas, apple and licorice, and fecal samples obtained from subjects on high-apple and licorice diets, were analyzed by head-space gas chromatography and gas chromatography-mass spectrometer. The volatile compounds characteristic of the odors of apple and licorice were detected by "sniffing" the GC effluent. The aromatic component of licorice was identified by GC-MS as anethole [1-methoxy-4-(2-propenyl) benzene]. The aromatic component of apple could not be chemically characterized by our GC MS system even though readily detected by the nose. Head-space, GC-MS analysis of fecal volatiles offers a means of tracing odorous and non-odorous components to ingested foodstuffs with potential applications to clinical and forensic medicine and anthropology. PMID- 4038302 TI - Comparison of bone inductive proteins of rat and porcine bone matrix. AB - Subcutaneous implantation of demineralized bone matrix in allogenic rats induces a sequence of events resulting in de novo formation of cartilage, bone and bone marrow. In the present study endochondral bone formation by demineralized porcine matrix was studied and compared with the rat bone matrix. Endochondral bone formation was induced by 4M guanidine hydrochloride fraction IV (less than 50,000 daltons) of Sepharose CL-6B gel filtration but not by whole extract or by demineralized porcine bone matrix. Sephacryl S-200 gel filtration of the osteoinductive proteins of fraction IV showed the Porcine osteoinductive factor to be associated with protein fraction III (less than 20,000 daltons) whereas the rat with fraction II (between 20,000 and 30,000 daltons) of the chromatographic profile indicating an apparent difference in molecular weight of the osteoinductive factors between these two species. PMID- 4038303 TI - Rat mammary gland in culture secretes a stable high molecular weight form of cathepsin L. AB - Culture medium from rat mammary gland explants was analyzed for the presence of cysteine proteinases. In addition to a putative precursor of the lysosomal enzyme cathepsin B, a cysteine proteinase with enzymatic properties similar to those reported for cathepsin L was found. Further evidence of the cathepsin L-like nature of this activity was provided by its high sensitivity towards the diazomethane inhibitors Z-Phe-Phe-CHN2 and Z-Phe-Ala-CHN2 and towards leupeptin. The secreted form of cathepsin L is distinguished from the lysosomal form by its increased stability at alkaline pH and by its larger molecular size. It may thus represent an incompletely processed precursor form of the lysosomal enzyme. PMID- 4038304 TI - Purification of bromoperoxidase from Corallina pilulifera. AB - Bromoperoxidase was purified from the crude extract of Corallina pilulifera (Corallinaeae, Rhodophyta) and found to be homogeneous upon disc gel electrophoresis by precipitation of ammonium sulfate and sequential column chromatographies of DEAE-Sepharose CL-6B, Sepharose 6B and Cellulofine GC-700m. The purified enzyme did not exhibit optical absorption spectra of a hemoprotein. Therefore, bromoperoxidase of C. pilulifera was completely distinguishable from other haloperoxidases which have heme-irons at the catalytic sites. PMID- 4038305 TI - Lack of lignin degradation by glucose oxidase-negative mutants of Phanerochaete chrysosporium. AB - Glucose oxidase-negative (gox-) mutants of Phanerochaete chrysosporium were isolated after exposing conidia to UV irradiation. The gox- mutants exhibited little or no ability to degrade lignin (2-[14C]-synthetic lignin to 14CO2); however, they retained other secondary metabolic features such as the ability to conidiate and produce veratryl alcohol, suggesting that they are not pleiotropic for secondary metabolism. Lignin degradation activity was restored in gox+ revertants. These results, in support of earlier evidence, indicate that glucose oxidase activity plays an important role in lignin degradation by P. chrysosporium. PMID- 4038306 TI - Differential effects of Nd-YAG laser on collagen and elastin production by chick embryo aortae in vitro. Relevance to laser angioplasty for removal of atherosclerotic plaques. AB - Aortae from 17-day old chick embryos were subjected to irradiation with a Nd:YAG laser at energy densities varying from 1.2 - 4.7 X 10(3) J/cm2. The aortae were pulse-labeled in vitro with [3H]proline or [14C]valine, and the synthesis of collagenous polypeptides and soluble elastin was examined by SDS-polyacrylamide gel electrophoresis, followed by fluorography and quantitative scanning densitometry. Irradiation of the aortae with Nd:YAG laser resulted in inhibition of the synthesis of the extracellular matrix proteins. The production of collagen was inhibited to a considerably larger degree than the production of elastin. Thus, the biosynthetic pathway for collagen production appears to be more susceptible to laser inhibition than the corresponding pathway for elastin production. These observations may have relevance to laser angioplasty which has been proposed to be applicable for removal of atherosclerotic plaques in human vessels. Specifically, the results suggest that inhibition of the extracellular matrix production may result in weakening of the vessel wall with subsequent aneurysm formation and rupture. PMID- 4038307 TI - Occurrence of the Y determinant on the N-glycosidic carbohydrate units of human gamma-seminoprotein. AB - 500-MHz H-NMR spectroscopy of the oligosaccharides derived from gamma seminoprotein, a human seminal plasma glycoprotein, revealed considerable microheterogeneity both with respect to the degree of branching and with regard to the peripheral sugars. Although the protein possesses only one N-glycosylation site, di-, tri- and tetra-antennary glycans in a ratio of 40:15:45 were found to be present. Moreover, certain branches of the tri- and tetra-antennas contain one or two Fuc residues which form part of the SSEA-1 and Y determinants. It should be noted that this is the first report that describes the occurrence and localization of the Y determinant, i.e. Fuc alpha (1----2)Gal beta (1----4) [Fuc alpha (1----3)]GlcNAc beta (1----.), in an N-glycan of a glycoprotein. PMID- 4038308 TI - The role of hexokinase as a possible modulator of Ca2+ movements in isolated rat brain mitochondria. AB - The present study shows that in brain mitochondria the active calcium uptake and the sodium-dependent calcium efflux are modulated by the porin-bound enzyme hexokinase. The release of the enzyme, promoted by glucose-6-phosphate (G-6-P), under conditions which do not affect mitochondrial functions, is accompanied by a decrease of the rates of fluxes of the cation. This phenomenon is discussed and correlated with the formation of microcompartments between the inner and outer mitochondrial membranes, where the hexokinase-porin complex may constitute a regulating gate system for calcium. PMID- 4038309 TI - Production of anti-sporozoite antibodies in absence of response to carrier by coupling an MDP derivative to a malaria peptide-tetanus toxoid conjugate. AB - A synthetic peptide (pep) representing a portion of the Plasmodium knowlesi circumsporozoite protein attached to a tetanus toxoid (TT) carrier, has been shown to be immunogenic when delivered in saline with derivatives of the synthetic adjuvant, muramyl dipeptide (MDP). The present study was designed to determine if the degree of substitution of pep and of MDP derivatives on the tetanus toxoid (TT) carrier, as well as the choice of MDP derivative used play a role in determining anti-pep and anti-TT antibody levels. One of the MDP derivatives used in the conjugates was epsilon-amino-caproic Murabutide, since Murabutide which is currently in clinical trials cannot be conjugated. The results show that low doses of this derivative coupled with pep on TT can be used to stimulate high levels of circulating anti-pep antibodies without augmenting the anti-carrier response. In addition, anti-pep antibodies elicited in response to one of the conjugates were biologically active since they produced shedding of the circumsporozoite coat of live parasites. PMID- 4038310 TI - Increase of the Fe effective charge in hemoproteins during oxygenation process. AB - The x-ray absorption near edge structure (XANES) spectra of hemoglobin and myoglobin have been measured at the wiggler beam line of the Frascati Synchrotron Radiation Facility. The energy shifts of the iron absorption jump edge and the chemical shifts of the bound excited state at threshold of 1s core excitations, going from deoxygenated to oxygenated form, are interpreted as evidence of some increase of the positive effective charge on the iron atom upon oxygenation. PMID- 4038311 TI - Disturbance of methyl group metabolism in alloxan-diabetic sheep. AB - Alloxan-induced diabetes results in changes in the activities of a number of enzymes related to methyl group metabolism in sheep. Decreases in the activities of phospholipid methyltransferase and betaine-homocysteine methyltransferase in diabetic sheep liver indicate a reduced rate of choline synthesis and oxidation. A 65-fold increase in the activity of glycine methyltransferase and a 4-fold rise in the activity of gamma-cystathionase in diabetic sheep liver with elevated urinary excretion of cyst(e)ine suggest that catabolism of the methyl group of methionine and homocysteine was enhanced in the diabetic state. PMID- 4038312 TI - Evidence for alpha-ketoglutarate dehydrogenase monomer activity with the aid of enzyme immobilization. AB - Immobilization of pigeon breast muscle alpha-ketoglutarate dehydrogenase on CNBr activated Sepharose 4B was carried out. Conditions for dissociation of the dimeric enzyme bound to the carrier via a single subunit were determined. Immobilized enzyme monomers with a specific activity higher than that of the dimer were obtained. The immobilized subunits are capable of reassociating with the soluble ones; this is accompanied by the restoration of the initial amount of the matrix-bound protein and the reconstitution of the activity typical of the immobilized enzyme original preparations. PMID- 4038313 TI - Study of properties of phosphorylase kinase using hydrophobic chromatography. AB - The structure of nonactivated and activated forms of phosphorylase kinase has been investigated. The enzyme activation was achieved by phosphorylation with cAMP-dependent protein kinase as well as by incubation of the enzyme in an alkaline medium (pH 8.8). For structural comparison of the enzymic forms, hydrophobic chromatography on phenyl-Sepharose and polyacrylamide gel electrophoresis were used. It has been shown that the enzyme activation results in a release of a low molecular weight component (Mr 16 000). The properties of this component resemble those of calmodulin. Evidence for the formation of an unstable nonactivated phosphorylase kinase - calmodulin complex may be important for the correct understanding of the mechanism of enzyme activation. PMID- 4038314 TI - Regulation of bacteriophage mu and mini-mu DNA replication in vivo. AB - To study the regulation of bacteriophage Mu DNA's integrative-replication (transposition) during lytic growth in a cell containing both a Mu and a helper dependent Mini-Mu (short, internally-deleted Mu genome), we placed "marker" genes (bla, lacZ) within either genome and then measured their encoded enzymes as indicators of the gene dosage. These results, corroborated using DNA-DNA hybridization, show that Mu and Mini-Mu DNA transposition is well regulated, requires both the Mu A and B gene products, and can be readily monitored by measuring beta-galactosidase and beta-lactamase expressed from the lacZ and bla genes, respectively. PMID- 4038315 TI - Thermophilic NAD-dependent glutamate dehydrogenase from Bacillus stearothermophilus. AB - A rapid purification procedure for glutamate dehydrogenase (GDH) from Bacillus stearothermophilus var calidolactis was developed. The homogeneous enzyme with a total molecular weight of approximately 240,000 daltons, contained 6 identical subunits. No high molecular weight form of GDH present in crude extracts was found after elution of the enzyme from a 5'AMP-Sepharose column with 4 M urea. The purified enzyme functions in both directions i.e. amination and deamination and is strictly specific for NAD. 2-Oxo glutarate, glutamate or 2-mercaptoethanol protects against heat inactivation. NADH or ammonia, on the other hand, makes GDH more sensitive to heat. The purified enzyme undergoes thermal inactivation process. PMID- 4038316 TI - A new plot for the kinetic analysis of dead-end enzyme inhibitors. AB - A new procedure to characterize reversible dead-end inhibitors is presented. Preliminary identification of the inhibitor type is made by plotting vo/vi against the inhibitor concentration at different substrate concentrations. The inhibition constants for competitive, uncompetitive and mixed dead-end inhibitors are determined by secondary plots of l/(slope) vs [S], l/(slope) vs l/[S] and (slope)(Ks + [S] vs [S] respectively. These secondary plots render straight lines only for their corresponding type of inhibitor. For noncompetitive inhibitors all the secondary plots used yield straight lines. Therefore, the application of this plotting procedure leads to unambiguous diagnosis of the inhibitor type. An important feature of the procedure presented here is that the variable used (vo/vi) is independent on Vmax values. Therefore, experimental values obtained from enzyme preparations showing significant differences in their specific activities -i.e. enzyme coming from different purification steps- can be used. PMID- 4038317 TI - Biochemical characterization of five glycoprotein molecules of the porcine zona pellucida. AB - Five glycoproteinmolecules with the molecular masses of 17 000; 38 000; 42 000; 50 000 and 67 000 were purified by high performance liquid chromatography following solubilization of isolated porcine zonae pellucidae by treatment with lithium-3,5-diiodosalicylate. The N-terminal amino acid residues were identified as arginine for 67 000, alanine for 50 000, arginine for 42 000, alanine for 38 000 and histidine for 17 000. The glycopeptides 42 000 and 17 000 were found to be rich on carbohydrates and 67 000 contained 7, 16% sialic acids. The latter moieties were tentatively identified as 5-N-acetylneuraminic acid, 5-N glycolylneuraminic acid and 5-N-acetyl-7,8,9 tri-O-acetylneuraminic acid. The five components of the zona were resolved by thin layer chromatography in a solvent system of propanol/butanol/HCl (2:1:1) and showed Rf-values of 0.17, 0.42, 0.46, 0.50 and 0.55 respectively. The glycoprotein with the molecular mass of 38 000 possesses spermatozoal receptor properties. This receptor molecule showed a pI of 5.9 upon isoelectric focusing. PMID- 4038318 TI - Elevated phosphate transporting activity and phosphate carrier content in mitochondria of rat hepatoma with high glycolytic capacity. AB - Transport of inorganic phosphate into Zajdela hepatoma mitochondria proceeds with approximately the same Km and about two times higher Vmax than the transport into mitochondria of rat liver. As detected by (a) titration of the inhibition of mitochondrial phosphate-stimulated respiration and phosphate-induced swelling by mersalyl and (b) binding of /14C/-NEM and /14C/-DCCD to a 33 kDa protein in mitochondria, the higher phosphate transporting activity of the hepatoma mitochondria is due to about a three fold increase in phosphate carrier content in the tumor mitochondria. PMID- 4038319 TI - Role of aspartate residues in the cardiac stimulatory activity of anthopleurin-A. AB - Modification of the polypeptide anthopleurin-A with a carbodiimide and glycine ethyl ester leads to the addition of nearly two Gly to AP-A. Limited amino acid sequence analysis shows that modification occurs principally at Asp-7 and Asp-9. The modified derivative shows no cardiac stimulatory activity. 1H nuclear magnetic resonance and circular dichroism spectra of the derivative show that its conformation is significantly altered. Thus, the Asp residues are essential for the cardiac stimulatory activity of AP-A, as well as for maintaining its native conformation. PMID- 4038320 TI - 14C labelling of octulose bisphosphates by L-type pentose pathway reactions in liver in situ and in vitro. AB - The complete reaction sequence of the pentose pathway in vitro was studied by incubating [1-14C] ribose 5-phosphate with rat liver enzyme preparation and assessed by both the rate and extent of formation of the glucose 6-P product. The reactions formed, as intermediates, the 1,8-bisphosphates of D-glycero D-ido octulose (D-g D-i Oct) and D-glycero D-altro octulose, both heavily labelled at C 4 with 14C isotope during the 12h incubation. The formation of the octulose phosphates and the specificity of their isotopic labelling confirms an important prediction of, and contribution by reactions of the L-type pentose phosphate pathway (L-PP) in liver in vitro. Infusion in situ of [6-14C] glucose into the liver of the anaesthetized rabbit resulted in the formation of high specific activity [8-14C] D-g D-i Oct 1,8-P2. The specificity of labelling indicates that the octulose intermediate is formed according to the options of the L-PP mechanism of glucose metabolism in intact liver. PMID- 4038321 TI - Iron chelation by pyridoxal isonicotinoyl hydrazone and analogues in hepatocytes in culture. AB - Pyridoxal isonicotinoyl hydrazone (PIH) and several analogues were synthesized and assessed in the rat hepatocyte culture for their potential in iron chelation therapy. Pyridoxal isonicotinoyl hydrazone and pyridoxal benzoyl hydrazone were as effective as desferrioxamine (DFO) in reducing both net uptake of rat transferrin-59Fe and incorporation into ferritin by hepatocytes. Dialysis studies showed that this was due to a cellular action and not to the extracellular chelation of transferrin-bound 59Fe. The analogues of PIH were more effective in mobilization studies than PIH and DFO, releasing more 59Fe from ferritin as well as from the stroma-mitochondrial membranes in hepatocytes prelabelled using transferrin-59Fe. Chelator action was dependent on incubation time, concentration, temperature and lipophilicity. Pyridoxal benzoyl hydrazone, the most effective iron chelator, was also the most lipophilic, suggesting that access to cellular iron compartments as well as iron-binding affinity is important in effective iron chelation. PMID- 4038322 TI - Modification of pulmonary metabolism of noradrenaline in experimental obstructive jaundice. AB - The pulmonary metabolism of noradrenaline (NA) was measured in lungs removed from 3 day sham-operated rats and from rats whose bile ducts had been ligated 3 days earlier (BDL). The pulmonary metabolism of NA as measured by a single clearance of the radio-labelled 14C-amine was significantly increased in lungs excised from BDL rats as compared to that measured in the sham-operated rats. The change in metabolism was associated with an alteration in the pulmonary uptake of NA and not with the activities of the enzymes monoamine oxidase types A and B and catechol-O-methyl transferase. Moreover, it was not correlated with rises in the bilirubin or cholesterol concentrations in the serum of the BDL rats and occurred independent of any changes in pulmonary pressure. In a second series of experiments, the evolution of this abnormality over the period of one to six days postoperative was investigated. In the sham-operated rats, there was no significant change in the pulmonary metabolism of NA even by the sixth day. In contrast, there were time-dependent increases from one to six days in these metabolic processes in BDL rats with the highest values being at six days. In contrast, the serum concentrations of bilirubin and cholesterol and activities of the enzymes, alanine transaminase and alkaline phosphatase all rose to their maximum by the fourth day and thereafter declined. Although serum albumin levels fell significantly in BDL rats they were not significantly different from sham controls. Thus, change in pulmonary metabolism of NA with obstructive jaundice increases with time from one to six days and it not related to the blood chemical changes of biliary obstruction or hepatic synthetic function. PMID- 4038323 TI - Inhibition of Trypanosoma brucei brucei peptidyl transferase activity by sparsomycin analogs and effects on trypanosome protein synthesis and proliferation. AB - Peptidyl transferase activity of Trypanosoma brucei brucei polyribosomes was competitively inhibited by analogs of sparsomycin (Ki = 1-100 microM). The analogs were also potent inhibitors of [3H]-leucine and [3H]mannose incorporation into the proteins of intact trypanosomes with little or no effect on overall respiratory rate, suggesting a specific site of action for these analogs on protein synthesis. The peptidyl transferase inhibitors were effective at low concentrations at limiting the proliferation of trypanosomes both in vitro and in vivo. The potency of the compounds as inhibitors of cell proliferation was positively correlated with their efficacy as inhibitors of peptidyl transferase activity. One compound, MDL 20828 (1 mg/kg), increased the survival time of T. b. brucei-infected mice 4-fold in the absence of any overt drug toxicity to the hosts. PMID- 4038324 TI - In vitro metabolism of diethylstilbestrol by hepatic, renal and uterine microsomes of rats and hamsters. Effects of different inducers. AB - In order to elucidate possible differences in the metabolism of the synthetic estrogen diethylstilbestrol (DES) by target and non-target tissues for DES carcinogenicity, the biotransformation of [14C]DES has been studied in vitro with hepatic and renal microsomes of male and female hamsters and rats, and from hamster and rat uterus. Of these tissues, only the male hamster kidney is susceptible to the carcinogenic effect of DES. Moreover, the effect of various inducers on the in vitro metabolism of DES has been investigated. It was found that male hamster kidney microsomes produced a markedly different pattern of DES metabolites as compared to renal microsomes from female hamster or male and female rats. Pretreatment with phenobarbital markedly increased oxidative DES metabolism by renal microsomes from female rat but not from male rat. Diethylstilbestrol metabolism by hepatic microsomes was different between hamster and rat, but was not sex-dependent and could not be significantly affected by pretreatment with phenobarbital, DES, 3-methylcholanthrene and 7:8-benzoflavone. The differences in DES metabolism between target and non-target organs and its modulation by inducers may help to gain further insight into the mechanism of DES tumorigenesis. PMID- 4038325 TI - The effects of some non-steroidal anti-inflammatory agents on membrane-associated calcium in rabbit peritoneal neutrophils. AB - Several non-steroidal anti-inflammatory agents (NSAIAs) (flufenamate, flurbiprofen, indomethacin, phenylbutazone, piroxicam and salicylate), one anti inflammatory steroid (hydrocortisone) and three compounds known to affect cellular calcium metabolism [nifedipine, calcium ionophore A23187, 8 (diethylamino)octyl 3,4,5,-trimethoxy benzoate hydrochloride (TMB-8)] were tested for their effects on membrane-associated calcium in rabbit peritoneal neutrophils using the fluorescent probe chlortetracycline (CTC). The NSAIAs reduced the level of fluorescence attained by incubating neutrophils with CTC, and caused an immediate reduction in the fluorescence of CTC-loaded neutrophils, both effects being concentration-related. Nifedipine, A23187 and TMB-8 also reduced the fluorescence of CTC-loaded cells. However, these measured reductions in fluorescence were due in whole or in part to a drug-induced drop in the autofluorescence of the neutrophils. After applying a correction factor which took account of this effect there was still an immediate concentration-related reduction in CTC-dependent fluorescence after the addition of all the NSAIAs. A23187 also caused a reduction in CTC fluorescence, but nifedipine, TMB-8 and hydrocortisone were inactive. Flufenamate, indomethacin and piroxicam reduced the drop in fluorescence brought about by N-formyl-methionyl-leucyl-phenylalanine (FMLP). These findings suggest that NSAIAs and A23187 displace membrane associated calcium. Electron microscopical findings confirm that indomethacin and salicylate both affect membrane-associated calcium. Using the fluorescent probe Quin 2, an attempt was made to determine whether or not the displacement of membrane-associated calcium by NSAIAs was accompanied by changes in cytoplasmic calcium ion concentration. This was unsuccessful, however, since the effects of the NSAIAs on the fluorescence of Quin 2-loaded neutrophils was accounted for almost entirely by their effects on the autofluorescence of the cells. PMID- 4038326 TI - In vitro formation of codeinone from codeine by rat or guinea pig liver homogenate and its acute toxicity in mice. AB - In vitro metabolism of codeine was investigated by using a 9000 g supernatant fraction of rat or guinea pig liver homogenate. When a mixture of [N-14CH3] and [C-6-3H]codeine was incubated with the rat liver 9000 g supernatant fraction in the presence of NAD, formation of codeinone, morphine and norcodeine was detected. Replacement of NAD with NADP abolished only the formation of codeinone. On the other hand, when the guinea pig liver homogenate was used in the presence of NAD, codeinone was the main metabolite of codeine. NADP was also ineffective in forming codeinone with the guinea pig liver homogenate. The acute toxicity of codeinone was thirty times higher than that of codeine. The roles of codeinone as a metabolic intermediate and in the acute toxicity of codeine are discussed. PMID- 4038327 TI - Trypanosomatid iron-superoxide dismutase inhibitors. Selectivity and mechanism of N1,N6-bis(2,3-dihydroxybenzoyl)-1,6-diaminohexane. AB - Crithidia, like trypanosomes and leishmania, has an iron-containing superoxide dismutase. The iron chelator N1,N6-bis (dihydroxybenzoyl)-1,6-diaminohexane proved to be a potent inhibitor of this enzyme. Inhibition of the crithidial superoxide dismutase by this compound was dependent on the presence of oxygen and associated with the formation of a complex which could not be dissociated by gel filtration chromatography. We propose that this biscatecholic inhibitor is first oxidized to a quinone which then covalently modifies a nucleophilic residue on the enzyme. This compound was less effective as an inhibitor of a mammalian copper- and zinc-containing superoxide dismutase. Thus, this inhibitor could serve as a prototype for the design of antiparasitic agents. PMID- 4038328 TI - Effects of antimicrotubule agents on phospholipid metabolism in rat hepatic subcellular membranes. AB - Treatment of animals with antimicrotubule drugs has been shown to cause a perplexing variety of cellular changes which, theoretically, could be the result of changes in endomembrane biosynthesis, composition or flow. In the current study we have focused on this possibility by identifying antimicrotubule drug induced changes in the phospholipid metabolism of hepatic subcellular membranes. Young adult rats were pretreated with radiolabeled [32 P]orthophosphate for 12 hr, and subsequently given saline, colchicine (2.5 mg/kg body wt) or vinblastine (20 mg/kg body wt) for 4 additional hr. Afterwards, the livers were homogenized, and separate microsomal and Golgi membrane fractions were prepared and subjected to phospholipid extraction and identification using two-dimensional thin-layer chromatography. The results show that colchicine and vinblastine given in vivo caused specific, rapid and in some cases, dramatic changes in phospholipid turnover in different membrane fractions of rat liver. The drugs specifically increased labeling of phosphatidylinositol-4-monophosphate and phosphatidylinositol-4,5-biphosphate and decreased the radioactivity associated with phosphatidylcholine, phosphatidylethanolamine and phosphatidylinositol in all fractions examined. In contrast, the antimicrotubule drugs produced a differential effect on the labeling pattern of sphingomyelin and lysophosphatidylcholine, i.e. they stimulated labeling of these phospholipids in microsomes, produced no changes in heavy Golgi fractions, and markedly increased their labeling in light Golgi fractions. These data suggest that antimicrotubule drugs restrict the incorporation of certain precursor phospholipids into forming membranes but do not affect the subsequent metabolism of these phospholipids. At the same time, the drugs appear to retard the flow of membranes from one cellular compartment to another. PMID- 4038329 TI - 16 alpha-Iodo-testosterone: chemical synthesis and evaluation as a potential radiopharmaceutical. AB - The chemical synthesis and characterization, including 1H NMR, of 16 alpha-iodo androstenedione and 16 alpha-iodo-testosterone are described. Each has been synthesized with 125I and tested in rats in vivo for accumulation in androgen dependent tissues over a 24 hr time course. Neither compound was accumulated in prostate against the blood gradient of normal or 24 hr castrate animals. The metabolism, subcellular distribution and binding of 16 alpha-[125I]iodo testosterone to protein in prostate has also been examined. By comparison with data obtained after the administration of [3H]testosterone we conclude that the failure of this iodinated androgen to accumulate in androgen dependent tissues arises because of its low binding affinity for receptor protein. PMID- 4038330 TI - Inhibition of acetylcholinesterase by neurotoxic aminonitriles. PMID- 4038331 TI - Hepatic drug-metabolizing enzymes in lung tumor-bearing rats. PMID- 4038332 TI - Effect of anticonvulsant drugs in vitro on pineal gland indole metabolism in organ culture. PMID- 4038333 TI - Immunochemical identification of an irreversibly bound heme-derived adduct to cytochrome P-450 following CCl4 treatment of rats. PMID- 4038334 TI - In vivo production of ethylene from 2-keto-4-methylthiobutyrate in mice. AB - The use of 2-keto-4-methylthiobutyric acid (KMB), the alpha-keto analog of methionine, was studied as a potential means of detecting free radical generation in vivo. KMB-dependent ethylene production (presumably from free radical interception), and ethane production from in vivo lipid peroxidation, were monitored simultaneously by measuring the rate of exhalation of these hydrocarbons by mice. Injection of KMB (1 g/kg) into mice resulted in an 8-fold increase in ethylene production above endogenous levels seen in saline-injected controls (1.47 +/- 0.35 vs 0.17 +/- 0.02 nmoles/100 g/hr respectively). Administration of CCl4 (3.0 g/kg) to initiate hepatic lipid peroxidation, 20 min prior to KMB injection, augmented the production of ethylene (2.37 +/- 0.10 nmoles/100 g/hr). Lipid peroxidation following injection of CCl4 was monitored via the increased exhalation of ethane. Pretreating the mice with vitamin E (100 mg/kg daily for 3 days), an inhibitor of lipid peroxidation, did not result in a significant change in ethylene production from KMB by itself or after prior injection of CCl4. However, vitamin E did suppress ethane production initiated by CCl4. Similar results were obtained with mouse liver slices studied in vitro. Metyrapone (150 mg/kg), an inhibitor of hepatic mixed function oxidase activity, also suppressed significantly the CCl4-stimulated production of ethane, but not the CCl4-stimulated production of ethylene from KMB. It appears that ethylene production from KMB does not derive from free radicals generated during in vivo lipid peroxidation since suppression of lipid peroxidation by vitamin E or metyrapone did not suppress ethylene production. PMID- 4038335 TI - 2-Chloroadenosine, a permeant for the nucleoside transporter. AB - Human erythrocytes were shown to possess a saturable uptake mechanism for 2 chloroadenosine (apparent Km 23 microM, 22 degrees). Uptake by this route was inhibited by nitrobenzylthioinosine, uridine and adenosine, but adenine had no effect. In addition, uridine caused the countertransport of 2-chloroadenosine and vice versa. 2-Chloroadenosine was also shown to be an apparent competitive inhibitor of uridine influx (apparent Ki value of 33 microM) and high-affinity nitrobenzylthioinosine binding (apparent Ki 0.18 mM). The apparent Ki value for inhibition of uridine influx was close to the apparent Km value for 2 chloroadenosine uptake. Previous studies [Jarvis et al., Biochem. J. 208, 83 (1982)] have demonstrated that dog erythrocytes do not possess a saturable transport system for uridine and adenosine. Similarly, in the present study, the entry of 2-chloroadenosine into dog erythrocytes was slow and linear with concentration. Nitrobenzylthioinosine (NBMPR) had no effect on the uptake of 2 chloroadenosine into dog erythrocytes. These results demonstrate that 2 chloroadenosine enters human erythrocytes by the same nucleoside carrier as other nucleosides. It is suggested from these data that the previous explanation that the inability of nucleoside transport inhibitors to potentiate the pharmacological effects of 2-chloroadenosine was due to the failure of the nucleoside carrier to accept 2-chloroadenosine as a permeant may have to be reassessed. PMID- 4038336 TI - DNA damage in normal and neoplastic mouse tissues after treatment with misonidazole in vivo. AB - Alkaline elution has been used to examine the integrity of DNA isolated from various tissues from mice treated with misonidazole (MISO). High doses (1-3 mg/g) of MISO caused extensive DNA strand breakage in cells isolated from two fibrosarcoma tumors that were known to contain hypoxic cells, and also in cells from certain normal tissues (liver and kidney in particular). The incidence of strand breaks gives further support to the suggestion that MISO can be metabolically nitroreduced beyond the singly reduced nitro radical-anion in some normal tissues as well as in hypoxic tumor cells, generating DNA-reactive species. Nitroreductases must therefore be able to compete successfully with molecular oxygen for the MISO nitro radical-anion in such tissues. PMID- 4038337 TI - Inhibition of rat liver hydroxymethylglutaryl-CoA reductase by sulfhydryl reagents, coenzyme A esters and synthetic compounds. AB - The activity of the microsomal 3-hydroxy-3-methylglutaryl-coenzyme A reductase was assayed with a procedure based on the extraction of the product mevalonolactone in a benzene phase. Diamide is an uncompetitive inhibitor of the reaction, while coenzyme A disulfide and tetraethylthiouram disulfide act as non competitive inhibitors. Diamide inhibition cooperatively increases with the inhibitor concentration. HMG produces a decrease in enzyme activity that combines with that of coenzyme A disulfide. Both CoASH and coenzyme A esters strongly inhibit the reductase activity. Three new synthetic compounds with either thio ether or thio-ester groups also show inhibitory effect on the enzyme activity. PMID- 4038338 TI - Evidence for the fatty acid-induced heterogeneity of the N and B conformations of human serum albumin. AB - The influence of oleic acid on the interaction between albumin and warfarin, oxyphenbutazone or diazepam has been studied by circular dichroism and equilibrium dialysis. The pH dependences of the molar ellipticity of the drug albumin complexes and of the free fraction of drug are completely changed by the presence of oleic acid. This phenomenon is attributed to an oleic acid-induced conformational change in both the neutral (N) and the basic (B) conformation of albumin, a change to which the warfarin-oxyphenbutazone binding area and the diazepam binding site is sensitive. The oleic acid-induced conformational states of albumin, the so-called N* and B* conformations, show binding properties that are different from the binding properties of the N and B conformations. PMID- 4038339 TI - Antithrombotic and bleeding effects of a low molecular weight heparin fraction. AB - Low molecular weight (LMW) heparin prevents venous thrombosis by potentiating the inhibition of coagulation factor Xa. Heparin, however, has other biological properties whose role in the prevention of thrombosis is still unknown. The aim of our study was to compare the antithrombotic activity of a LMW heparin and its parent molecule in an attempt to understand better the mechanism and structural requirements for heparin's antithrombotic effect. We studied a preparation of an unfractionated pig mucosal heparin pure by any accepted criteria (electrophoresis in various systems, conductimetric titration and NMR spectra) and a LMW heparin fraction obtained from the former by fractional precipitation with ethanol. Both heparins completely prevented thrombus formation in an experimental model of stasis-induced venous thrombosis in rats. When administered intravenously to rats, the unfractionated heparin had an ex vivo anti-Xa/APTT ratio of 1.67, versus 6.60 of the LMW heparin fraction. Unexpectedly, both heparins induced a significant prolongation of tail bleeding time, performed by two different techniques, the "transection" (mostly exploring blood clotting) and the "template" (exploring the platelet/vessel wall interactions). This study suggests that, beside anticoagulation, other effects may play a role in both the antithrombotic and haemorrhagic effects of some heparins and LMW heparin fractions. PMID- 4038340 TI - Role of fluroacetate in the toxicity of 2-fluroethylnitrosoureas. AB - The possible role of fluroacetate in the toxicity and antitumour activity of the fluroethylnitrosoureas, BFNU and FCNU has been studied in CBA mice bearing the TLX5 lymphoma either sensitive (TLXS) or resistant (TLXRT) to nitrosoureas. Treatment of mice bearing either TLXS or TLXRT tumours with either BFNU or FCNU caused an elevation in the citrate levels of heart, kidney and tumour, but not the liver, 24 hr after drug administration. Heart citrate levels were maximally elevated 10-fold, while the levels in kidney and tumour were increased 3- to 6 fold. Tissue levels of flurocitrate were determined by glc after conversion to the ethyl ester. This showed maximum levels of fluroacetate production in heart, with lower levels in kidney, tumour and liver. Treatment of K562 human erythroleukaemia cells in vitro with BFNU caused an inhibition in the production of 14CO2 from 14C palmitate and [U-14C] glucose. These results suggest that some of the effects of the fluroethylnitrosoureas may be related to fluroacetate production and the consequent blocking effect on aconitase. This effect is probably related more to the generalized toxicity of these agents than to their therapeutic efficacy. PMID- 4038341 TI - Drug-induced shape change in erythrocytes correlates with membrane potential change and is independent of glycocalyx charge. AB - The influence of the anionic drugs indomethacin, barbitone, salicylate and the cationic drugs chlorpromazine and tetracaine on the morphology of human erythrocytes suspended in solutions of different chloride concentration (thus altering cell membrane potential) and constant osmolality, has been examined. As expected, the anionic and cationic drugs produced echinocytes and stomatocytes respectively in 145 mM NaCl. The cationic drugs induced fewer stomatocytes in 60 mM chloride than in 145 mM chloride at 37 degrees. Tetracaine induced echinocytes in 60 mM chloride at 20 degrees. Indomethacin and barbitone produced echinocytes in 145 mM chloride and stomatocytes in 60 mM chloride. Salicylate no longer produced echinocytes when the chloride concentration was reduced. Cells exposed to salicylate in 60 mM chloride were less cupped than the control cells. We suggest that the distribution of the charged form of the drug across the membrane is in equilibrium with the distribution of chloride ions. Changes in the intracellular drug concentration when the extracellular chloride is varied could then account for the observed shape changes in a manner which is consistent with the bilayer couple hypothesis for drug-membrane interactions. Cell glycocalyx charge depletion did not affect the shape induced by either the cationic or anionic drugs. The result suggests that any sialic acid dependent electric potential at the bilayer surface is small compared to the cell's zeta potential. PMID- 4038342 TI - Effect of 4-(4'-chlorobenzyloxy)benzyl nicotinate (KCD-232) on cholesterol metabolism in rats. AB - The effects of 4-(4'-chlorobenzyloxy)benzyl nicotinate (KCD-232), a new hypolipidemic agent, on serum cholesterol level and cholesterol biosynthesis were studied in normolipidemic rats. KCD-232 dose-dependently reduced the serum cholesterol level. The in vivo incorporation of [14C]-acetate and 3H from [3H]water into liver digitonin-precipitable sterols was inhibited by oral administration of KCD-232, while that of [14C]mevalonic acid into the sterols was not inhibited. Hepatic 3-hydroxy-3-methylglutaryl (HMG)-CoA reductase activity was suppressed significantly by the oral administration of the drug. A KCD-232 metabolite, 4-(4'-chlorobenzyloxy)benzoic acid (MII), strongly inhibited [14C]acetate incorporation and weakly inhibited [14C]mevalonic acid incorporation into the sterols in liver slices. MII also significantly inhibited the sterol synthetic rate measured with [3H]water and the HMG-CoA reductase activity in dispersed hepatocytes. MII and its CoA thioester (MII-CoA) inhibited the incorporation of [14C]acetate, [14C]acetyl-CoA and [14C]HMG-CoA into nonsaponifiable lipids in a cell-free enzyme system from rat liver. MII-CoA further showed a weak inhibition of [14C]-mevalonic acid incorporation into nonsaponifiable lipids in the system, while MII showed no effect on mevalonic acid incorporation. These results indicate that KCD-232 possesses a major inhibitory site for sterol synthesis on HMG-CoA reductase due to both MII and MII CoA, and a possible second site of action beyond mevalonic acid due to MII-CoA. The latter inhibitory site, however, is considered to play a minor role in the inhibition of sterol synthesis in vivo. PMID- 4038343 TI - The effect of 5-thioglucose on the energy metabolism of Schistosoma mansoni in vitro. AB - 5-Thioglucose (5-TG) had a marked effect on the energy metabolism of Schistosoma mansoni in vitro: the conversion of external glucose into lactate by intact worms was severely inhibited. This inhibition of glycolysis was instantaneous, independent of the oxygen concentration and competitive with respect to glucose. Degradation of 0.5 mM external (14C-labelled) glucose was inhibited for 80% in the presence of 20 mM 5-TG. On the other hand the degradation of endogeneous glycogen to lactate was uninhibited. This shows that the inhibition of glucose breakdown occurred at the entrance of glucose into the cell and/or at the hexokinase reaction. It was demonstrated that 5-TG inhibited both the uptake of glucose and the activity of hexokinase. However, it was concluded that in the intact worm 5-TG blocked glycolysis by its competitive inhibition of hexokinase. In intact S. mansoni worms hexokinase is probably the rate-limiting enzyme of glycolysis. Krebs-cycle activity and lactate production do not occur at a fixed ratio: at lower rates of pyruvate formation Krebs-cycle activity was favoured. PMID- 4038344 TI - Comparative study on the metabolism of N-methyl-4-aminoazobenzene by two forms of cytochrome P-488. PMID- 4038345 TI - Transport of 42K+, 201Tl+ and [99mTc(dmpe)2.Cl2]+ by neonatal rat myocyte cultures. PMID- 4038346 TI - Hymenoxon: biologic and toxic effects. PMID- 4038347 TI - Inactivation of catalase with 3-amino-1,2,4-triazole: an indirect irreversible mechanism. PMID- 4038348 TI - [Synthesis, cloning and determination of the primary structure of a full-size DNA copy of the neuraminidase gene from influenza virus type A subtype H1N1]. AB - Complete nucleotide sequence of the cloned full-length DNA copy of the influenza virus A (H1N1) neuraminidase gene has been determined. The predicted amino acid sequence is compared with sequences of neuraminidases from other influenza virus strains. A section of the neuraminidase is found to be homologous to the chicken lysozyme catalytic centre. PMID- 4038349 TI - [Synthesis, cloning and determination of the primary structure of a full-size DNA copy of the NP protein gene from influenza virus type A]. AB - Complete nucleotide sequence of the cloned full-length DNA copy of the influenza virus A (H1N1) RNA segment 5 has been determined. The degree of nucleotide difference between two variants of A/PR/8/34 strain is estimated. The possible secondary structure of the segment 5 is deduced from the nucleotide sequence of some clones. PMID- 4038350 TI - [Synthesis, cloning and determination of the primary structure of a full-size DNA copy of fragment 8 from the influenza virus type A genome]. AB - Complete nucleotide sequence of the cloned full-length DNA copy of the influenza virus A (H1N1) RNA segment 8 has been determined. A section of the hypothetical protein coded for by the negative strand of the segment 8 is found to be homologous to the trypsin catalytic centre. PMID- 4038351 TI - [Synthesis of leucine- and methionine-enkephalin using papain]. AB - Thiol protease papain has been used for synthesis of leucine-and methionineenkephalin from methyl esters of N-protected amino acids. The synthesis was carried out in basic medium, minimizing the hazard of the secondary peptide hydrolysis. The reaction products remain in solution during the whole process. The yields at the final stage of the synthesis were 89% (leucineenkephalin) and 79% (methionineenkephalin). PMID- 4038352 TI - [Heterogeneity of carbohydrate fragments in heavy and light chains of influenza virus A/Leningrad/385/80 (H3N2) hemagglutinin]. AB - Comparative analysis of carbohydrate chains variations in influenza virus A/Leningrad/385/80 (H3N2) hemagglutinin (HA) and its heavy (HA1) and light (HA2) chains has been carried out. The carbohydrate chains of these three glycoproteins were eliminated by reductive cleavage of N-glucosaminidic linkages under LiBH4 - tert-BuOH treatment. Fractionation of the oligosaccharides thus obtained by means of gel chromatography and HPLC resulted in isolation of 21 individual oligosaccharides from each glycoprotein. Their monosaccharide composition revealed almost identical pattern of high-mannose as well as complex chains in HA1 and HA2 in spite of different number (6-7 in HA1 and only 1 in HA2) of glycosilated sites. The possibility of a great number of both high-mannose and complex chains attached at the same site of glycoprotein is shown. PMID- 4038353 TI - [Synthesis and analysis of glycol bis-phosphates, regulators of reversible hemoglobin oxygenation]. AB - Bisphosphates of glycols, ethyleneglycol and 1,2-propanediol, were synthesized. These structural analogues of 2,3-diphosphoglyceric acid were shown to reduce significantly the oxygen affinity of stripped hemoglobin. PMID- 4038354 TI - [New concepts of microsomal metabolism of the antibiotic adriamycin]. AB - Experimental and literary data are presented which are at variance with the known conception of adriamycin (AD) shunting the chain of microsomal electron transfer. AD, carminomycin, rubomycin, mitomycin C, and coenzyme Q9 are shown to interact with NADPH, in the absence of enzymes, with the nucleotide oxidation. A new scheme of AD metabolism is suggested, according to which AD in the hydroquinone form enters the chain of electron transfer in microsomes between NADPH and flavoprotein. PMID- 4038355 TI - Synthesis, secretion, and deposition of fibronectin in cultured human synovium. AB - We examined fibronectin synthesis, secretion, and deposition in vitro by primary explants of rheumatoid synovium. Primary cultures initiated from tissue with monocytic infiltrates had higher levels of fibronectin synthesis; addition of dexamethasone at concentrations known to stimulate other tissue fibroblasts increased fibronectin synthesis and secretion. Newly synthesized fibronectin recovered from primary rheumatoid culture medium had a higher apparent molecular weight (240-245 kd), on sodium dodecyl sulfate-polyacrylamide gel electrophoresis, compared with fibronectin recovered from passaged normal and rheumatoid cultures (230 kd). Primary rheumatoid explant cultures had a characteristic morphology which correlated with fibronectin deposition. Dense deposits of fibronectin extracellular matrix covered overlapping synoviocytes adjacent to esterase-positive mononuclear cells. Dexamethasone-treated cultures showed little fibronectin deposited as extracellular matrix and did not develop overlapping cellular networks. Characteristic patterns of fibronectin synthesis and deposition in primary rheumatoid cultures appear to result from interaction between fibroblastic and monocytic cells. This culture system may provide a model by which to study interactions between cells and extracellular matrix components that regulate synovial cell function. PMID- 4038356 TI - Morphologic and cytochemical changes in maturing and osteoarthritic articular cartilage in the temporomandibular joint of mice. AB - We studied the light microscopic, ultrastructural, and cytochemical characteristics of the temporomandibular joints of male ICR mice, from early neonatal life until they reached senescence, when spontaneous osteoarthritis is a common phenomenon. Aging of mandibular condylar cartilage was accompanied by decreasing total proteoglycan content and by an unmasking of collagen fibers, with no shift in collagen type. Fibronectin was also commonly present on the articular surface of specimens from old animals. Chondrocytes of aged mice contained an increased number of lysosomes, and their adjacent matrix vesicles reacted positively for acid phosphatase and arylsulfatase, but not for alkaline phosphatase. Such vesicles were also found to be devoid of calcium complexes and, thus, did not appear to be involved in the mineralization process. Similar age related changes have been described in human mandibular condyles; hence, the male ICR mouse could serve as a useful model for studies of spontaneous osteoarthritis in the human mandibular joint. PMID- 4038357 TI - Synovial amyloidosis in patients undergoing long-term hemodialysis. AB - Synovial amyloid deposits were found in 18 patients with end-stage renal failure due to various nonamyloid nephropathies, who had been treated with long-term, periodic hemodialysis (mean 116 months). All patients had carpal tunnel syndrome, which was bilateral in 14 of them; 4 patients also had finger flexor tenosynovitis. In 2 patients, destructive arthropathies required surgical replacement of the hip. Amyloid deposits were demonstrated by light microscopy in the synovium of the finger flexor tendon and/or transverse carpal ligament of all patients who had surgery for carpal tunnel syndrome, and in the synovium and capsula of the 2 surgically removed hips. Transmission electron microscopy of synovial samples from 6 patients demonstrated the characteristic fibrillar ultrastructure of amyloid deposits, the biochemical nature of which is still unknown. In addition, 9 patients had cystic radiolucencies of bone, which were interpreted as having resulted from local amyloid deposits, involving carpal bones, humeral heads, femoral heads, acetabula, or tibial plateaus. Our results show that amyloidosis is a frequent histologic finding in dialysis patients receiving surgical management of carpal tunnel syndrome, and that it can also be associated with cystic radiolucencies of bones and with destructive arthropathies. PMID- 4038358 TI - The syndrome of anserina bursitis: an overlooked diagnosis. PMID- 4038359 TI - Production of immunoglobulin and rheumatoid factor by lymphoid cells in rheumatoid pericardium. PMID- 4038360 TI - Erosive azotemic osteoarthropathy: possible role of amyloidosis. PMID- 4038361 TI - Anticentromere antibody is not specific for connective tissue disease with a promising prognosis. PMID- 4038362 TI - Congenital heart block, systemic lupus erythematosus, and anti-Ro antibodies. PMID- 4038363 TI - Cyclosporine: a new adjuvant therapy for giant cell arteritis? PMID- 4038364 TI - Reflex sympathetic dystrophy associated with malignancy. PMID- 4038365 TI - The clinical features of elderly-onset rheumatoid arthritis. A comparison with younger-onset disease of similar duration. AB - Patients with elderly-onset rheumatoid arthritis (EORA) may represent a clinical subset of individuals who differ prognostically and therapeutically from patients with younger-onset disease (YORA). In order to test this hypothesis, we reviewed the records of 212 patients with rheumatoid arthritis and grouped them according to age at onset above or below 60 years old. Seventy-eight EORA patients and 134 YORA patients with disease duration of less than or equal to 10 years were used for a comparison of presenting features and disease outcome. Abrupt onset occurred somewhat more frequently in EORA, but was not associated with a significantly different clinical course than was an insidious presentation in this older group. There were no differences between the EORA and YORA groups in terms of mean initial joint score, although the scores for the YORA group had wider variation. An initial clinical presentation resembling polymyalgia rheumatica (PMR) was 4 times as frequent in EORA. Elderly patients were less likely to have subcutaneous nodules or rheumatoid factor at disease onset. At the final examination, the EORA patients had lower joint scores and higher health assessments despite similar courses of treatment. These outcome differences persisted when patients with PMR-like presentations were excluded. Multivariate analyses indicated that joint scores and disease duration made important contributions to a better outcome of EORA, whereas PMR presentation and abrupt onset did not. After an adjustment was made for these 4 features, age at onset was an important contribution to joint score outcome. These results confirm the existence of important differences in onset, clinical features, and prognosis between patients with EORA and those with YORA. PMID- 4038366 TI - Some experimental pain indices and their applications in the study of analgesic mechanisms. AB - This communication presents some insights into the controversies and complications in experimental pain research using laboratory animals. In particular, I have singled out two experimental pain indices that are used in my laboratory for a decade, viz, dental pain model and hot-plate algesiometric assay for discussion. Using these two models, my colleagues and I have identified that morphine may promote analgesia by enlisting synergistic actions from the central cholinergic and dopaminergic systems, in a process that involves shifting of balance between various neurotransmitter systems. We confirmed the medullary nucleus reticularis gigantocellularis as a site for clonidine- and morphine induced and stimulation-produced antinociception. Finally, a progressive increase in pain sensitivity and a gradual reduction in the analgesic potency of morphine and clonidine are unveiled in aging rats. PMID- 4038367 TI - The adherence to human endothelium and plastic of neutrophils from psoriatic patients, and the effects of psoriatic patients' sera on normal neutrophils. AB - Circulating polymorphonuclear neutrophils (PMNs) from 50 patients with psoriasis vulgaris and from 38 control individuals (28 healthy blood donors and 10 patients with systemic sclerosis) were tested for their ability to adhere to human endothelial cell monolayer and a plastic surface. We also studied the effect of sera from psoriatic patients on the adherence and chemotactic activity of normal human neutrophils. The neutrophils from patients with psoriasis were much more adherent to the endothelium and the plastic surface, and this correlated positively with the activity of the disease, but inversely with the extent of the skin lesion. The sera from patients with active psoriasis were found to enhance the adherence and chemotaxis of normal human PMNs. Treatment of the sera by heat (56 degrees C for 30 min) did not affect their enhancing effect on the adherence but significantly decreased their effect on the chemotactic activity of normal PMNs. PMID- 4038369 TI - Heritability of cardiac size: an echocardiographic and electrocardiographic study of monozygotic and dizygotic twins. AB - Because of the uncertainty as to the extent to which cardiac size is determined by exercise training vs genetic endowment, this study investigated familial (genetic plus common family environment) vs nonfamilial influences on cardiac size. College-age monozygotic twins (group 1, 31 sets), dizygotic twins (group 2, 10 sets), siblings of like sex (group 3, six sets), and nonrelated subjects (group 4, 15 sets) underwent echocardiographic and electrocardiographic tests, measurement of maximum oxygen uptake (VO2max), and evaluation of pulmonary and body composition; mean intrapair differences of the four groups were compared. Mean intrapair differences in cardiac size varied as much for subjects in group 1 as for those in groups 2 and 3. However, subjects in groups 1, 2, and 3 had less variation (p less than .05) than those in group 4. After the initial testing, 14 pairs of monozygotic twins, five sets of dizygotic twins, and six sets of siblings underwent 14 weeks of exercise training (both members participated) and all tests were repeated. After exercise training, subjects in group 1 still had as much intrapair variability in cardiac size as those in groups 2 and 3. The data suggest cultural familial influences are more important in determining cardiac size than nonfamilial influences or even genetic influences alone. PMID- 4038368 TI - Clinical pharmacology in patients with evolving myocardial infarction of tissue type plasminogen activator produced by recombinant DNA technology. AB - This study was performed to characterize selected pharmacologic properties and effects on the fibrinolytic system of tissue-type plasminogen activator synthesized by recombinant DNA technology (rt-PA) in 12 patients treated for coronary thrombosis. rt-PA was infused parenterally (by the intracoronary route in four patients and intravenously in eight) in doses of 8.3, 12.5, or 16.7 micrograms/kg/min for 30 to 60 min, yielding a total dosage of 20 to 40 mg/patient. The drug induced coronary thrombolysis in 10 of the 12 patients treated (83%), including six of the eight given rt-PA intravenously. No bleeding complications were encountered. Serial blood samples were obtained before, during, and after infusion of rt-PA and analyzed for t-PA antigen (i.e., immunoassayable rt-PA protein), functional fibrinolytic activity attributable to rt-PA, fibrinogen, plasminogen, alpha 2-antiplasmin, fibrinogen degradation products, prothrombin time, activated partial thromboplastin time, and protamine corrected thrombin time. Pretreatment plasma t-PA antigen levels averaged 16.5 +/ 5(SD) ng/ml. Peak plasma values were generally proportional to dose, averaging 3330 +/- 1201 ng/ml. Approximately 90% of peak level was reached in 30 min, with a plateau at peak reached within 40 min. Functional t-PA activity increased monotonically in a comparable fashion. Curves for disappearance of both t-PA antigen and functional activity from plasma were monoexponential for at least two half-lives (r = .99 for both) and were concordant. The observed half-lives were similar, averaging 8.3 and 9.1 min, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4038370 TI - Apical hypertrophic cardiomyopathy: evaluation by noninvasive and invasive techniques in 23 patients. AB - Over a 3 year period we evaluated 23 patients (16 men, seven women) with apical hypertrophic cardiomyopathy by noninvasive and invasive methods. Sixteen patients had chest pain. In 17, results of cardiovascular examination were normal. The electrocardiogram showed precordial inverted T waves in all patients and these were of mild-to-moderate amplitude (less than 10 mm) in 18 and giant (greater than 10 mm) in five. M mode echocardiography revealed a typical pattern of contraction and relaxation in the apical region of the left ventricle that was associated with significant hypertrophy. These findings were confirmed by two dimensional echocardiography. Systolic anterior motion of the mitral valve was not observed nor was there any evidence of obstruction of the left ventricular outflow tract. Results of Doppler echocardiographic study of the mitral and aortic flow were normal in all patients but one who had mild mitral insufficiency. Radionuclide studies of 14 patients revealed a mean left ventricular ejection fraction of 66 +/- 6% (range 55% to 79%), with normal left ventricular contraction in all patients but two with apical hypokinesis. In all six patients who underwent catheterization a characteristic appearance of the left ventricle at end-systole as well as abnormal end-diastolic contour were noted on the left ventricular angiogram, but the "ace of spades" configuration was seen in only one. We conclude that the 23 patients studied form a homogeneous group of individuals with nonobstructive apical hypertrophic cardiomyopathy, which differs in many respects from cardiomyopathies reported by other investigators. PMID- 4038371 TI - Lipid peroxidation: a mechanism for ethanol-associated testicular injury in rats. AB - Chronic alcohol administration leads to hepatic membrane alterations which, at least in part, are due to lipid peroxidation and may contribute to the toxicity of ethanol at the level of the hepatocyte. Because changes in testicular function also occur after chronic administration of ethanol to rats, we evaluated testicular mitochondria for evidence of alcohol-associated peroxidation injury which might contribute to the gonadal injury that occurs with prolonged use of the drug. Lipid peroxidation was assessed through measurement of diene conjugates, polyenoic fatty acid composition, malonaldehyde formation, and testicular reduced glutathione levels. Compared to isocalorically matched dextrimaltose-fed controls (ISO), rats fed alcohol (ETOH) for 50 days had a decreased content of polyenoic acids and a compensatory increase in saturated fatty acids [ETOH, 50.69 +/- 0.65% (by wt); ISO, 52.93 +/- 0.72 (mean +/- SE); P less than 0.01]. This decrease in polyunsaturated fatty acid content was accompanied by an increase in diene conjugates in testicular mitochondria (ETOH, 0.455 +/- 0.053 OD units at 233 nm/mg lipid; ISO, 0.382 +/- 0.045; P less than 0.05). An increase in malonaldehyde formation also was observed in the alcohol fed rats compared to the control level (ETOH, 21.39 +/- 1.67 nmol/mg protein; ISO, 17.50 +/- 1.39; P less than 0.05) as well as a decrease in glutathione content (ETOH, 1218 +/- 89 micrograms GSH/testes; ISO, 1638 +/- 89; P less than 0.05). Taken together, these findings support the concept that lipid peroxidation may be an important mechanism responsible, at least in part, for the toxic effect of ethanol on the testes. PMID- 4038372 TI - Age- and diabetes-related changes in tissue glucose uptake and estradiol accumulation in the C57BL/KsJ mouse. AB - The effect of the diabetes (db/db) mutation on the age-related changes in glucose uptake and estradiol incorporation in peripheral tissues were investigated in C57BL/KsJ mice between 2 and 16 wk of age. Glucose uptake in the uterus, ovaries, pancreas, lung, liver, heart, kidney, and spleen were markedly increased in diabetic mice after the development of the hyperglycemic condition, as compared with control mice. The age-related increase in glucose uptake observed in control mice was enhanced in hyperglycemic (i.e., greater than or equal to 4 wk of age) animals. In contrast, the diabetes mutation caused a decreased estradiol uptake by the uteri, ovaries, and mesometrial fat pads at 16 wk, while having little effect in nontarget tissues of diabetic mutants. These data indicate that the diabetes mutation enhances glucose uptake, especially in estradiol target tissues (i.e., uterus, ovary), at the same time that estradiol incorporation is depressed. These results suggest that an alteration in glucose utilization by steroid-sensitive reproductive tract tissue may underlie the impaired reproductive ability in these animals. Other peripheral tissues did not demonstrate any remarkable changes in estradiol uptake, but the enhanced carbohydrate metabolism observed may relate to the subsequent age- and diabetes related changes in tissue structure and function in these animals. PMID- 4038373 TI - Thrombolysis with recombinant tissue plasminogen activator in atherosclerotic thrombotic occlusion. AB - Human tissue plasminogen activator holds promise for the dissolution of coronary thrombi by intravenous administration and without systemic anticoagulation. Prior animal experiments have been conducted only in vessels without disease. To test the thrombolytic efficacy of recombinant tissue plasminogen activator in the presence of diseased intima, an established model of atherosclerosis was utilized. The aorta of 16 New Zealand white rabbits (2 to 3 kg) was made atherosclerotic by balloon endothelial denudation and concurrent 1% cholesterol feeding for 8 weeks. An aged (24 hour) heterologous (human) clot, labeled with I 125 fibrinogen was injected into the distal aorta and produced thrombotic occlusion. After 1 hour of thrombosis (control period), recombinant tissue plasminogen activator (100,000 IU approximately equal to 1 mg protein, n = 6) or streptokinase (100,000 IU, n = 5) or saline solution (n = 5) was systemically infused over 30 minutes. Serial blood samples, obtained to determine fractional change in blood radioactivity over time, showed a fourfold increase of blood radioactivity after tissue plasminogen activator and streptokinase infusion compared with the control period (47,400 +/- 3,300 [mean +/- standard error] versus 11,800 +/- 300 counts/min, p less than 0.001). Time to 50% of maximal thrombolysis was 41 +/- 14 minutes (+/- standard deviation) for tissue plasminogen activator versus 63 +/- 16 minutes for streptokinase (p less than 0.01). In six of six rabbits receiving tissue plasminogen activator and four of five rabbits receiving streptokinase, reestablishment of distal aortic flow was detected via the indwelling catheter within 25 minutes of drug infusion.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4038374 TI - Surgical management of urinary incontinence in girls with congenitally short urethra. AB - We treated 6 girls with total urinary incontinence secondary to a congenitally short urethra by a combination of extensive internal and external urethral lengthening. Of the patients 3 had hypospadias and 3 had severe epispadias. All 6 are dry during the day and 1 has nighttime wetting. Success depends upon the creation of a long neourethra and a new continence zone. PMID- 4038375 TI - Peer assessment. PMID- 4038376 TI - Cisplatin ototoxicity in gynecologic cancer patients. A preliminary report. AB - The ototoxicity associated with long-term cisplatin therapy in gynecologic cancer patients was investigated. Twenty-three of 31 patients developed hearing loss and 21 patients reported the onset of tinnitus. The hearing loss was bilateral, cochlear, and permanent. The tinnitus was transient and not predictive of change in hearing level. The likelihood of developing hearing loss appeared to be greatest in patients older than 40 years and in patients with preexisting hearing loss. The amount of change did not appear to be related to the degree of preexisting hearing loss. PMID- 4038377 TI - Hereditary ovarian carcinoma. Biomarker studies. AB - Three ovarian-cancer-prone kindreds were studied, two of which contained identical twin sisters concordant for ovarian carcinoma. In one kindred, both identical twin sisters had daughters with ovarian carcinoma. In another kindred, one of the identical twin sisters had an ovarian-cancer-affected daughter. Ovarian carcinoma showed vertical transmission in all three families in a pattern consonant with an autosomal dominant mode of inheritance. Medical-genetic survey of each family included detailed questionnaires with retrieval of primary medical and pathology documents on cancer of all anatomic sites. Putative biomarker determinations included: (1) in vitro hyperdiploidy in dermal monolayer cultures; and (2) lower serum levels of alpha-L-fucosidase (less than or equal to 275 IU/ml) in all cancer-affected patients and statistically significant lower levels in 50% risk individuals when compared to spouse and published controls (P = 0.04 and P = 0.0002, respectively). These findings are discussed in context with the eventual development of a risk factor profile which, given acceptable sensitivity and specificity, would enable identification of individuals who would be prime candidates for intensive surveillance/management programs. PMID- 4038378 TI - Erythrocyte mean corpuscular volume during cytotoxic therapy and the risk of secondary leukemia. AB - Erythrocyte mean corpuscular volume (MCV) evolution during cytotoxic therapy of Hodgkin's disease, lymphoma, multiple myeloma, ovarian cancer, and breast cancer was studied. The fastest and the highest MCV increases were observed in the diseases and with the therapies the most frequently involved in secondary leukemia: Hodgkin's disease treated with MOPP (mechlorethamine, vincristine, procarbazine, prednisone), and multiple myeloma and ovarian cancer treated with melphalan. On the contrary, with cytotoxic regimens not linked to a high frequency of secondary leukemia such as CMF (cyclophosphamide, methotrexate, 5 fluorouracil) used in ovarian or breast cancer, MCV increase was moderate. As the MCV increase reflects the bone marrow reaction to cytotoxic therapy, an unusually high increase could indicate bone marrow damages which could lead to secondary leukemia. PMID- 4038379 TI - Rapid loss of stress fibers in Chinese hamster ovary cells after hyperthermia. AB - This study was initiated to characterize the effect of hyperthermia (45 degrees) on the distribution of actin stress fibers in Chinese hamster ovary cells using rhodamine-conjugated phalloidin, a probe specific for F-actin. Fluorescent microscopy revealed a rapid loss of stress fibers after immersion in a 45 degrees water bath. After 5-min immersion at 45 degrees, approximately 90% of the cells analyzed did not contain observable stress fibers. Stress fibers were visible after incubation of cells at 37 degrees after heating. The recovery of the appearance of the stress fibers occurred as protein synthesis resumed, and addition of protein synthesis inhibitors following heat treatment blocked the reappearance of these structures. These results support the hypothesis that cytoskeletal components may be a target of hyperthermia, explaining the pleotropic biological effects of heat and, in particular, heat radiosensitization. PMID- 4038380 TI - Antiinvasive effect of racemic 1-O-octadecyl-2-O-methylglycero-3-phosphocholine on MO4 mouse fibrosarcoma cells in vitro. AB - Alkyl-lysophospholipids have been shown to possess antitumoral activity in animal and in human tumors. Among them, racemic 1-O-octadecyl-2-O-methylglycero-3 phosphocholine (ET-18-OCH3) had an antimetastatic effect in experimental tumors. We investigated the effect of ET-18-OCH3 on invasion of MO4 mouse fibrosarcoma cells and on cellular activities possibly related to invasion in vitro. Ten micrograms of ET-18-OCH3 per ml permitted growth of MO4 cells to about 75% of controls and slightly reduced trypan blue exclusion. Directional migration inferred from the area covered by MO4 cells that had migrated from an aggregate on glass was not affected. Reassembly of microtubules after treatment with 1 microgram of Nocodazole per ml occurred normally in presence of ET-18-OCH3. Invasion was completely inhibited when MO4 cell aggregates were confronted with precultured fragments of embryonic chick cardiac muscle or with fresh embryonic chick lung fragments in culture on gyratory shaker in fluid medium with 10 micrograms of ET-18-OCH3 per ml. These experiments showed that ET-18-OCH3, in contrast with microtubule inhibitors, interfered with invasion of MO4 cells in vitro at concentrations that permitted growth and directional migration of MO4 cells. Fluorescence polarization studies with the lipophylic probe diphenylhexatriene indicated that the antiinvasive effect of ET-18-OCH3 was accompanied by an overall increase of membrane fluidity. We tentatively concluded that alterations of the MO4 cellular membranes are responsible for the antiinvasive effect of ET-18-OCH3. PMID- 4038381 TI - Comparative activity and distribution studies of five platinum analogues in nude mice bearing human ovarian carcinoma xenografts. AB - The antitumor activity of four new platinum analogues was compared at equitoxic doses to that of cisplatin in B10 LP/cpb nude mice bearing xenografts of human ovarian carcinomas. The two tumor lines used, MRI-H-207 and Pe, differ in histology, tumor doubling time, and sensitivity to cisplatin. Complete remission of MRI-H-207 was observed with cisplatin, carboplatin, iproplatin, and JM-40, while spiroplatin only gave growth delay. Cisplatin and carboplatin caused some growth delay of Pe, while JM-40, spiroplatin, and iproplatin failed to affect tumor growth. Platinum tissue distribution was also measured for each compound in groups of five to seven tumor-bearing mice. Platinum concentrations in the two tumors at 24 hr were similar for cisplatin and carboplatin, but differed for iproplatin, spiroplatin, and JM-40. Organ distribution was similar for each analogue, and concentrations were significantly higher in kidneys than in liver, except for iproplatin with comparable concentrations in these organs. Our findings show a good correlation between analogue activity in ovarian cancer in the clinic and that in MRI-H-207. Platinum concentrations in tumor tissue did not predict antitumor activity. PMID- 4038382 TI - Clinical pharmacology of high-dose cisplatin. AB - Although nephrotoxicity has frequently limited conventional treatment with cisplatin to doses of 100-120 mg/m2 per cycle, vigorous chloruresis can permit the administration of high-dose cisplatin (200 mg/m2 per cycle) with minimal nephrotoxicity. Systemic toxicities are worsened, but therapeutic response seems to be enhanced. The pharmacokinetics of cisplatin in plasma and urine were examined to assess the causes of these effects. Plasma disappearance of ultrafiltrable platinum was well-described by a single exponential for each patient. The mean t1/2 was 50% longer for patients receiving high-dose cisplatin than for patients receiving conventional doses. The total systemic exposure was three times greater in the high-dose group, which tends to explain the systemic toxicity and improved tumor efficacy, but not the lack of nephrotoxicity. It is suggested that the kidneys of patients in the high-dose group were relatively protected by dilution of active Pt species in the urine in the tubule lumen as well as by high chloride ion concentrations in the urine. PMID- 4038383 TI - Myocardial ischemia in patients with hypertrophic cardiomyopathy: contribution of inadequate vasodilator reserve and elevated left ventricular filling pressures. AB - To study the mechanism and hemodynamic significance of myocardial ischemia in hypertrophic cardiomyopathy, 20 patients (nine with resting left ventricular outflow tract obstruction greater than or equal to 30 mm Hg) with a history of angina pectoris and angiographically normal coronary arteries underwent a pacing study with measurement of great cardiac vein flow, lactate and oxygen content, and left ventricular filling pressure. Compared with 28 control subjects without hypertrophic cardiomyopathy, their resting coronary blood flow was higher (91 +/- 27 vs 66 +/- 17 ml/min; p less than .001) and their coronary resistance was lower (1.13 +/- 0.38 vs 1.55 +/- 0.45 mm Hg/ml/min; p less than .001). Left ventricular end-diastolic pressure (16 +/- 6 vs 11 +/- 3 mm Hg; p less than .001) and pulmonary arterial wedge pressure (13 +/- 5 vs 7 +/- 3 mm Hg; p less than .001) were significantly higher in patients with hypertrophic cardiomyopathy. During pacing, coronary flow rose in both groups, although coronary and myocardial hemodynamics differed greatly. In contrast to the linear increase in flow in control subjects up to heart rate of 150 beats/min (66 +/- 17 to 125 +/- 28 ml/min), patients with hypertrophic cardiomyopathy demonstrated an initial rise in flow to 133 +/- 31 ml/min at an intermediate heart rate of 130 beats/min. At this point, 12 of 20 patients developed their typical chest pain. With continued pacing to a heart rate of 150 beats/min, mean coronary flow fell to 114 +/- 29 ml/min (p less than .002), with 18 of 20 patients experiencing their typical chest pain and metabolic evidence of myocardial ischemia. This fall in coronary flow was associated with a substantial rise in left ventricular end-diastolic pressure (30 +/- 9 mm Hg immediately after peak pacing). In the 14 patients whose coronary flow actually fell from intermediate to peak pacing, the rise in left ventricular end-diastolic pressure in the same interval was greater than that of the six patients whose flow remained unchanged or increased (11 +/- 8 vs 2 +/- 2 mm Hg; p less than .01). In addition, despite metabolic and hemodynamic evidence of myocardial ischemia, the arteriovenous O2 difference actually narrowed at peak pacing. Thus most patients with hypertrophic cardiomyopathy achieved maximum coronary vasodilation and flow at modest increases in heart rate. Elevation in left ventricular filling pressure, probably related to ischemia-induced changes in ventricular compliance, was associated with a decline in coronary flow.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 4038384 TI - Acetylcholine receptor antibody-producing cells in thymus and lymph nodes in myasthenia gravis. AB - Eleven patients with myasthenia gravis (5 with thymoma) were studied and spontaneous production of antibody to acetylcholine receptor (AChR) in vitro was found by thymus cells in 10 (and in all 5 with thymoma) and by lymph node cells in 8 (and in 3 with thymoma). The rate of AChR antibody production by thymus cells was greater than that by lymph node cells (10.7 +/- 11.6 and 1.4 +/- 1.5 fmol/10(6) cells/week, respectively, mean +/- SD, P less than 0.05 by paired t test), although the B-cell population was always smaller in the thymus than in the lymph nodes (9.5 +/- 9.4 and 31 +/- 12.7%, P less than 0.001), suggesting the principal role of the thymus in AChR antibody production. It is suggested that lymph nodes can be one of the main sites of AChR antibody production in myasthenia gravis but the antibody-producing cells may originate in the thymus. PMID- 4038385 TI - Metoclopramide kinetics at high-dose infusion rates for prevention of cisplatin induced emesis. AB - Eleven male subjects aged 24 to 58 yr received cisplatin, 90 to 120 mg/m2 iv, in combination with other cytostatic drugs such as doxorubicin HCl and bleomycin. To prevent emesis, two high-dose metoclopramide regimens were started 2 hr before cytostatic therapy. Regimen A (n = 7) consisted of a loading dose infusion of 1 mg/kg/hr over 2 hr, followed by a maintenance infusion of 0.5 mg/kg/hr over 24 hr (total dose was 14 mg/kg in each cytostatic cycle). Regimen B (n = 6) consisted of half the metoclopramide dose. The following kinetics were derived from the metoclopramide steady-state plasma levels and the t1/2 of the elimination phase 26 to 38 hr after dosing (median value and range are listed): Steady-state plasma concentration in group A and group B was 750 (480 to 1520) and 360 (300 to 480) ng/ml plasma. Drug clearance in group A and group B was 0.67 (0.3 to 1.0) and 0.70 (0.5 to 0.8) l/hr/kg. Volumes of drug distribution in group A and group B were 4.4 (1.9 to 6.5) and 4.3 (3.2 to 5.9) l/kg. Values for the t1/2 in the elimination phase in group A and group B were 4.7 (3.0 to 5.4) and 4.3 (3.7 to 5.1) hr. It appears that metoclopramide kinetics at high doses were dose linear, i.e., without evidence of cumulation. There were few side effects; vomiting was effectively suppressed by both regimens. PMID- 4038386 TI - Dual effect of procaine in sea urchin eggs. Inducer and inhibitor of microtubule assembly. AB - An increase in the amount of cytoplasmic filamentous structures (cytoplasmic matrix and aster) which were recovered after hexylene glycol/Triton X-100 treatment of sea urchin eggs (Paracentrotus lividus) activated by 0.2-2.5 mM procaine was observed. At higher activator concentrations, an opposite effect was observed and formation of these cytoplasmic structures was inhibited in the presence of 10 mM procaine. This inhibitory effect was reversed by diluting the drug in the incubation medium. DNase I inhibition assays on egg homogenates which were performed at different time points of the activation process, show that the same amount of actin was induced to polymerize in eggs activated either by 2.5 or 10 mM procaine. However, colchicine-binding assays on the 100 000 g particulate fractions of these homogenates show that in eggs activated by 10 mM procaine, in contrast to those activated by 2.5 mM, tubulin polymerization was inhibited and microtubules were disassembled. These results show that the dual effect of procaine in the organization of the egg cytoskeleton appears to be related to its effect on the state of tubulin. PMID- 4038387 TI - Improved negative staining of microfilament arrangements in detergent-extracted Physarum amoeboflagellates. AB - A motile, lamellipodium-like structure, the ridge, forms as amoeboflagellate cells of Physarum polycephalum release from a substratum and begin swimming in fluid. Actin microfilaments form a distinct laminar core within the ridge; they are seen as a sparse, disordered meshwork in cytoskeletons prepared by conventional methods using uranyl acetate negative staining [10]. Preservation and visualization of these filaments and their arrangements improved considerably when cytoskeletons were imaged with phosphotungstic acid buffered with ammonium hydroxide (PTA(NH4]. Microfilaments within ridge cytoskeletons were found to form loose bundles and criss-crossing, 'meshwork' arrays several layers deep. Differences could be detected in morphology and detailed arrangement of microfilaments within cytoskeletons prepared in the presence of phalloidin. PTA(NH4) may be useful for studies of cytoskeletal elements and their rearrangements in dynamic, motile regions of cells. PMID- 4038388 TI - Serum androgenic hormones motivate sexual behavior in adolescent boys. AB - In order to separate hormonal from social effects on adolescent male sexual behavior, serum hormone assays were performed and questionnaire data on sexual motivation and behavior were collected on a representative sample of 102 boys in grades 8, 9, and 10 of a public school system. Free testosterone was a strong predictor of sexual motivation and behavior, with no additional contribution of other hormones. Including measures of pubertal development and age (indexing the effects of social processes) indicated no additional effects. Free testosterone, therefore, appears to affect sexual motivation directly and does not work through the social interpretation of the accompanying pubertal development. PMID- 4038389 TI - Alteration of the anterior-posterior embryonic axis: the pattern of gastrulation in macrocephalic frog embryos. AB - The production of an enlarged head or macrocephaly in frog embryos can be achieved by interspecific hybridization or by injection of the contents of the germinal vesicle (GV), the large nucleus of immature oocytes, into the blastocoels of embryos before they gastrulate. The macrocephalic embryos have large suckers and their neural tubes are larger anteriorly but smaller posteriorly as compared to controls. This abnormal syndrome has previously been thought to arise as a result of an axial structure determinant present in the germinal vesicle. When examined during gastrulation, however, Xenopus laevis and Rana pipiens macrocephalic embryos produced by GV injection as well as macrocephalic embryos produced by the hybrid cross, Rana septentrionalis female X Rana catesbeiana male, all exhibit alterations in the pattern of gastrulation. The most striking of these alterations is the persistence throughout gastrulation of a thick blastocoel roof composed of many cell layers, suggesting that there is an inhibition of posterior spreading of the roof normally associated with epiboly. In R. pipiens, the dorsal mesodermal mantle of GV-injected gastrulae is thicker as compared to controls, accounting for a neural plate which is wide at the anterior end. Vital dye mapping experiments on Xenopus laevis embryos show that dye marks placed on regions normally fated to become trunk epidermis become localized anteriorly when the embryos are GV injected, consistent with the idea that ectodermal cells are inhibited from moving posteriorly. These results indicate that the macrocephalic syndrome can be attributed to a localized inhibition of cell rearrangements during gastrulation as opposed to the effects of altered inducers or to axial determinants. PMID- 4038390 TI - Clinical pharmacology of intraperitoneal cisplatin. AB - The clinical pharmacology of cisplatin was determined in six patients with malignant ascites secondary to ovarian cancer, and in one patient with peritoneal mesothelioma, following intraperitoneal administration of cisplatin (25-60 mg/m2). The drug was administered in 1 liter of normal saline as a 15- to 30-min infusion. Total, and in some patients free (ultrafilterable), platinum concentrations were determined in plasma, urine, and ascitic fluid by flameless atomic absorption spectrometry. The peak total platinum concentrations in ascitic fluid at the end of infusion were related to dose, a 50 mg/m2 dose producing a 20 to 80 micrograms cisplatin/ml concentration. Filterable platinum represented between 3 and 59% of total platinum in the peritoneum at 4 to 6.5 hr following its administration. Plasma platinum concentrations ranged between 0.2 to 1.6 micrograms/ml 4 hr following administration, and reached a plateau for the next 24 to 48 hr largely in the form of protein-bound platinum. The urinary excretion of cisplatin was consistent with variation in absorption from the peritoneum. Minimal gastrointestinal, bone marrow, and renal toxicities during therapy suggest that sustained free platinum concentrations in ascites may be obtained without significant toxicity and support the intraperitoneal route of administration as an effective strategy for cisplatin therapy of intra-abdominal malignancies. PMID- 4038391 TI - The effect of cytoxan, adriamycin, and cis-platinum on cervical, vaginal cytology. AB - One hundred and thirty-four cervical and vaginal smears were obtained from 51 patients receiving cyclophosphamide, doxorubicin, and cis-platinum. These drugs do not appear to cause dysplasia or significant atypia. Additionally, the Pap smear was not useful for the diagnosis of unexpected persistent or recurrent carcinoma of the ovary. PMID- 4038392 TI - Public hospitals can survive PPS, cut LOS. PMID- 4038393 TI - Medical technology under PPS: an uncertain future. PMID- 4038394 TI - Painless primary herpes. AB - An adolescent male developed painless but severe genital ulcerations. Evaluation confirmed primary herpes. The medical literature describes the classical presentation of primary genital herpes infection as multiple ulcerations and severe pain, but 5% of male patients present without pain. Consequently, the differential diagnosis of painless genital ulcerations should include Herpes progenitalis. PMID- 4038395 TI - Canine hemangiosarcoma: retrospective analysis of 104 cases. AB - Hemangiosarcoma was diagnosed in 104 dogs. The mean age was 10 years. Twenty-two breeds were represented. The most common were the German Shepherd Dog and Poodle. Most tumors were in the spleen (65/104). Other primary sites included the soft tissues of the trunk and extremities (18), liver (6), heart (3), and lung (2). Sixty of the dogs were examined because of rupture of the primary tumor or metastatic disease. Of the 104 dogs, 4 are alive and 100 are dead: 35 were euthanatized at the time of diagnosis, and the remaining 65 had a mean survival time of 123 days. The mean survival time of the 4 living dogs was 360 days. Forty seven of the 65 dogs with splenic hemangiosarcoma were treated with surgery alone, surgery and immunotherapy, or surgery, immunotherapy, and combination chemotherapy. The same 47 dogs were clinically staged. There was no difference in survival time according to therapy or stage of disease. PMID- 4038396 TI - A single enzyme catalyzes the synthesis of the mannosylphosphoryl derivative of dolichol and retinol in rat liver and Chinese hamster ovary cells. AB - It is well established that mannosylphosphoryldolichol participates in the synthesis of N-linked glycoproteins by donating mannosyl residues to oligosaccharide-lipid intermediates. It has been suggested that mannosylphosphorylretinol also is involved in glycoprotein biosynthesis. We conclude that one synthase catalyzes the synthesis of both mannosylphosphoryldolichol and mannosylphosphorylretinol in rat liver tissue and Chinese hamster ovary cells, based on the following results. 1) The enzyme in rat liver microsomes that synthesizes mannosylphosphoryldolichol and mannosylphosphorylretinol is inactivated at the same rate at 55 degrees C. 2) In membranes of both rat liver and Chinese hamster ovary cells, exogenous dolichyl phosphate and retinyl phosphate compete with each other for mannosyl-lipid synthesis. However, in both systems adding exogenous retinyl phosphate has no effect on the synthesis of mannosylphosphoryldolichol from endogenous dolichyl phosphate in the membranes. 3) Membranes prepared from a mutant of Chinese hamster ovary cells which is devoid of mannosylphosphoryldolichol synthase lack the ability to synthesize mannosylphosphorylretinol. PMID- 4038397 TI - Decreased transfer of oligosaccharide from oligosaccharide-lipid to protein acceptors in regenerating rat liver. AB - The transfer of [14C]glucose from UDP-[14C]glucose to lipid intermediates and glycoproteins was decreased in regenerating rat liver microsomes 24 h after partial hepatectomy. In regenerating liver microsomes, the concentration of free dolichyl phosphate (Dol-P) was significantly decreased. However, it was only about 10% of total Dol-P, which was not significantly changed. On the addition of exogenous Dol-P, the transfer of [14C]glucose to glycoproteins was still decreased, while the decrease of the transfer to lipid intermediates was no longer observed. These results suggest that the glycoprotein synthesis is not regulated by the amount of Dol-P in regenerating liver microsomes. Oligosaccharide obtained from [14C]glucosyl-oligosaccharide-lipid was not distinguishable between regenerating liver and control by paper chromatography. The oligosaccharide transfer to protein in microsomes was compared by using [14C]glucosyl-oligosaccharide-lipid as oligosaccharide donor. The transfer of oligosaccharide to endogenous proteins decreased to 77% of control in regenerating liver and the transfer to exogenously added denatured alpha lactalbumin decreased to 59% of control. Therefore, it is unlikely that the acceptor capacity of endogenous protein is decreased in regenerating liver. Neither the change in oligosaccharide-lipid under the condition for oligosaccharide transfer assay nor the stability of oligosaccharide transferase was different between regenerating liver and control. These results strongly suggest that the decrease in the activity of the oligosaccharide transferase in microsomes causes the decrease of glycoprotein synthesis in regenerating liver, which was shown in our previous studies. PMID- 4038398 TI - The total length of spindle microtubules depends on the number of chromosomes present. AB - We extracted chromosomes by micromanipulation from Melanoplus differentialis spermatocytes, producing metaphase spindles with only one or a few chromosomes instead of the usual complement of 23. Cells with various numbers of chromosomes were prepared for electron microscopy, and spindle microtubule length was measured. A constant increment of microtubule length was lost upon the removal of each chromosome; we estimate that only approximately 40% of the original length would remain in the total absence of chromosomes. Unexpectedly, kinetochore microtubules were not the only ones affected when chromosomes were removed: nonkinetochore microtubules accounted for a substantial fraction of the total length lost. No compensatory increase in microtubule length outside the spindle was found. Studies by others show that the kinetochore microtubules of extracted chromosomes are left behind in the cell and dissassemble. The resulting increase in subunit concentration would be expected from in vitro studies to drive microtubule assembly until the original total microtubule length was restored, but that did not happen in these living cells. We conclude that the assembly of a certain, large fraction of microtubule subunits into stable microtubules is dependent on the presence of chromosomes. Possible explanations include (a) limits on microtubule length that prevent any net assembly of the subunits released after chromosomes are removed or (b) a promotion of microtubule assembly by chromosomes, which therefore is reduced in their absence. Chromosome-dependent regulation of microtubule length may account for some features of normal mitosis. PMID- 4038399 TI - The rat liver mitochondrial DNA-protein complex: displaced single strands of replicative intermediates are protein coated. AB - Mitochondrial DNA (mtDNA)-protein complexes were released from the organelles by sodium dodecyl sulfate-lysis and purified by Phenyl-Sepharose CL-4B chromatography. The mitochondrial DNA-binding protein P16 was the only detectable protein in the complex. Treatment of the complex with proteinase K, or subtilisin, revealed the presence of a protease-insensitive, submolecular domain (Mr approximately equal to 6,000) that retained the capacity to bind tenaciously to the DNA. Analysis of chemically fixed complexes by CsCl isopycnic gradient centrifugation showed that P16 was bound to a large subpopulation of mtDNA enriched in displacement loops (D-loops). Based upon the effective buoyant density of the complex in CsCl gradients and the molecular weights of P16 and mtDNA, it was estimated that a mean of 49 P16 molecules were bound per mtDNA. For this measurement, the variation in hydration of protein and DNA at different CsCl concentrations was ignored. Analysis of restriction endonuclease-digested complexes by glass fiber filters that bind only protein-associated DNA resulted in the retention of a single fragment regardless of the enzyme, or enzymes, used. In each case, the retained fragment was the D-loop-containing fragment. With direct electron microscopy, the protein was readily visualized on the displaced single strand portions of D-loops and expanding D-loops. The nucleoprotein fibers were approximately 12 nm in diameter without correcting for the thickness of tungsten coating and roughly 1/3 the length of the double strand segment of the corresponding D-loop structure. In addition, occasional molecules with the characteristics of gapped circles were seen exhibiting a nucleoprotein fibril, presumably containing the single strand gap segment, linking the ends of double strand DNA. P16 was not seen on the double strand portions in any of the complexes. PMID- 4038400 TI - Purification and general properties of the DNA-binding protein (P16) from rat liver mitochondria. AB - The mitochondrial DNA-binding protein P16 was isolated from rat liver mitochondrial lysates by affinity chromatography on single strand DNA agarose and separated from DNA in the preparation by alkaline CsCl isopycnic gradients. The top fraction of the gradients contained a single polypeptide species (Mr approximately equal to 15,200) based upon SDS PAGE. Digestion of single strand DNA-bound P16 with proteinase K produced a protease-insensitive, DNA-binding fragment (Mr approximately equal to 6,000) that has been purified by essentially the same procedures used for intact P16. The partial amino acid compositions for P16 and the DNA-binding fragment were obtained by conventional methods. Analysis of subcellular fractions revealed that nearly all of the cellular P16 was located in the mitochondria and that only trace amounts of protein of comparable electrophoretic mobility could be isolated from the nuclear or cytoplasmic fractions. The labeling of P16 with [35S]methionine in primary rat hepatocyte cultures was inhibited by more than 90% by the cytoplasmic translation inhibitor cycloheximide, but unaffected by the mitochondrial-specific agent chloramphenicol. These results indicate that P16 is synthesized on cytoplasmic ribosomes and imported into the mitochondria. The addition of purified P16 to deproteinized mitochondrial DNA resulted in the complete protection of the labeled nascent strands of displacement loops against branch migrational loss during cleavage of parental DNA with SstI, thus providing strong evidence that P16 is the single entity required for this in vitro function. Incubation of P16 with single strand phi X174 DNA, double strand (RF) phi X174 DNA, or Escherichia coli ribosomal RNA and subsequent analysis of the nucleic acid species for bound protein indicated a strong preference of P16 for single strand DNA and no detectable affinity for RNA or double strand DNA. Examination of P16-single strand phi X174 DNA complexes by direct electron microscopy revealed thickened, irregular fibers characteristic of protein-associated single strand DNA. PMID- 4038402 TI - Forskolin induction of S-100 protein in glioma and hybrid cells. AB - The S-100 protein level in mouse neuroblastoma (N18TG-2 and NIE-115), rat glioma (C6, C6BU-1, and C6V-1), and hybrid (NG108-15, 140-3, 141-B, NBr10A, NBr20A, NCB20, and NX3IT) cells was determined with a sensitive enzyme immunoassay system that uses a rabbit antibody to bovine brain S-100 protein. S-100 protein was detected in glioma but not in neuroblastoma cells. All seven hybrid cells derived from neuroblastoma and glioma or other types of cells were found to possess a very little or undetectable S-100 protein. The induction of S-100 protein level in prestationary phase cultures of glioma C6BU-1 cells was examined by forskolin, which was a highly specific activator of adenylate cyclase of the cells and produced morphological differentiation. After incubation with 10 microM forskolin for 48 hr, the S-100 protein level increased 2-2.5-fold in C6BU-1 glioma cells whose mean control level was 60 +/- 26 ng/mg protein (+/- SD). The forskolin induction of S-100 protein in the cells was dose dependent, and the concentration of forskolin required for 50% activation of S-100 protein was about 0.6 microM. The increase by forskolin was initiated from 10-15 hr after incubation with it and was inhibited with cycloheximide and actinomycin D. In NG108-15 hybrid cells the induction of S-100 protein was also observed by forskolin as well as prostaglandin (PG) E1 plus theophylline which are known to activate adenylate cyclase of the cells. The results indicate that S-100 protein biosynthesis is genetically controlled in these clonal cells, and that S-100 protein can be regulated in a cAMP-dependent fashion in prestationary cultures. PMID- 4038403 TI - Resolution of acromegaly, amenorrhea-galactorrhea syndrome, and hypergastrinemia after resection of jejunal carcinoid. AB - A young woman presented with acromegaly and amenorrhea-galactorrhea with hypersomatotropinemia and hyperprolactinemia. In addition, she had hypergastrinemia with abnormal secretory dynamics and evidence of a large pituitary tumor with suprasellar extension and erosion of the floor of the sella turcica. Evaluation of secretory diarrhea revealed a large abdominal tumor, which on removal was found to be a carcinoid of the jejunum. Postoperatively, the acromegaly, amenorrhea-galactorrhea, and hypergastrinemia resolved, and the pituitary returned to normal size, with regrowth of the sella floor. The carcinoid tumor was shown by immunoperoxidase staining to contain GH-releasing hormone. PMID- 4038401 TI - Microtubule-associated protein 2 within axons of spinal motor neurons: associations with microtubules and neurofilaments in normal and beta,beta' iminodipropionitrile-treated axons. AB - We have examined the distribution of microtubule-associated protein 2 (MAP2) in the lumbar segment of spinal cord, ventral and dorsal roots, and dorsal root ganglia of control and beta,beta'-iminodipropionitrile-treated rats. The peroxidase-antiperoxidase technique was used for light and electron microscopic immunohistochemical studies with two monoclonal antibodies directed against different epitopes of Chinese hamster brain MAP2, designated AP9 and AP13. MAP2 immunoreactivity was present in axons of spinal motor neurons, but was not detected in axons of white matter tracts of spinal cord and in the majority of axons of the dorsal root. A gradient of staining intensity among dendrites, cell bodies, and axons of spinal motor neurons was present, with dendrites staining most intensely and axons the least. While dendrites and cell bodies of all neurons in the spinal cord were intensely positive, neurons of the dorsal root ganglia were variably stained. The axons of labeled dorsal root ganglion cells were intensely labeled up to their bifurcation; beyond this point, while only occasional central processes in dorsal roots were weakly stained, the majority of peripheral processes in spinal nerves were positive. beta,beta' Iminodipropionitrile produced segregation of microtubules and membranous organelles from neurofilaments in the peripheral nervous system portion and accumulation of neurofilaments in the central nervous system portion of spinal motor axons. While both anti-MAP2 hybridoma antibodies co-localized with microtubules in the central nervous system portion, only one co-localized with microtubules in the peripheral nervous system portion of spinal motor axons, while the other antibody co-localized with neurofilaments and did not stain the central region of the axon which contained microtubules. These findings suggest that (a) MAP2 is present in axons of spinal motor neurons, albeit in a lower concentration or in a different form than is present in dendrites, and (b) the MAP2 in axons interacts with both microtubules and neurofilaments. PMID- 4038404 TI - Effect of uracil arabinoside on metabolism and cytotoxicity of cytosine arabinoside in L5178Y murine leukemia. AB - Pretreatment of L5178Y murine leukemia cells with uracil arabinoside (ara-U) enhances the cytotoxicity of cytosine arabinoside (ara-C). This effect is mediated by the cytostatic effect of ara-U, which causes a delay of cell progression through S-phase. Consequently, the specific activity of enzymes that peak during S-phase increases, and deoxycytidine kinase increases 3.6-fold over untreated controls. This allows enhanced anabolism of ara-C to nucleotides, as well as increased incorporation into DNA with ultimate synergistic cytotoxicity. It is postulated that the systemic metabolism of high-dose ara-C to sustained high levels of ara-U in patients with acute leukemia may enhance the activity of subsequent doses of ara-C, and thus contribute to a means for pharmacologic self potentiation, contributing to the unique therapeutic activity of high-dose ara-C. PMID- 4038406 TI - Coronary thrombolysis and infarct size reduction after intravenous infusion of recombinant tissue-type plasminogen activator in nonhuman primates. AB - Occlusive thrombus was produced by thrombin-induced coagulation in the left anterior descending coronary artery (LAD) of 16 open-chest baboons. In six control animals, occlusive thrombosis persisting over a period of 4 h as evidenced by coronary arteriography resulted in large transmural infarction (63.1 +/- 3.5% of the perfusion area). In 10 animals, tissue-type plasminogen activator obtained by recombinant DNA technology (rt-PA) was infused systemically at a rate of 1,000 IU (10 micrograms)/kg per min for 30 min after 30-80 min of coronary thrombosis. Reperfusion occurred within 30 min in nine animals. In one animal, intravenous infusion was followed by an intracoronary infusion at the same rate, which resulted in thrombolysis within 8 min. In the rt-PA group, mean duration of occlusion before reperfusion was 77 +/- 24 min. Reocclusion occurred in one animal. Recanalization resulted in an overall reduction of infarct size (37.8 +/- 5.9%, P less than 0.05 versus controls). Residual infarction was related to the duration of occlusion (r = 0.80, P less than 0.01). Reperfusion was associated with reduced reflow. Myocardial blood flow in the perfusion area of the LAD was only 70% of normal after 4 h despite perfect angiographic refilling. The infusion of rt-PA was not associated with systemic activation of the fibrinolytic system, fibrinogen breakdown, or clinically evident bleeding. It is concluded that intravenous infusion of rt-PA may recanalize thrombosed coronary vessels without inducing systemic lysis. The extent of residual infarction is closely related to the duration of coronary artery occlusion before thrombolysis. PMID- 4038405 TI - Vitamin D status regulates 25-hydroxyvitamin D3-1 alpha-hydroxylase and its responsiveness to parathyroid hormone in the chick. AB - We asked this question: Under normal or near-normal metabolic conditions, does the prevailing normal or near-normal vitamin D status dampen the activity of 25 hydroxyvitamin-D3-1 alpha-hydroxylase (1 alpha-hydroxylase) such that it determines not only its "basal" activity but also its responsiveness to stimulation by increased circulating concentrations of parathyroid hormone (PTH)? To answer this question, we measured the activity of 1 alpha-hydroxylase in chicks, with and without administration of PTH, immediately before and during deprivation of vitamin D. Before deprivation of vitamin D, 1 alpha-hydroxylase activity increased only slightly with administration of PTH. With deprivation of vitamin D for 5 and 10 d, while the plasma concentrations of calcium and phosphorus persisted normal and unchanged, 1 alpha-hydroxylase activity not only increased progressively but also became sharply and increasingly responsive to stimulation by administration of PTH. But after 15 d of vitamin D deprivation, and the supervention of hypocalcemia, 1 alpha-hydroxylase activity was not further increased by the administration of PTH. With deprivation of vitamin D, the progressive increase in 1 alpha-hydroxylase correlated inversely with circulating levels of 1,25-dihydroxyvitamin D (1,25-[OH]2D), and the decreasing calcemic response to PTH correlated inversely with the responsiveness of 1 alpha hydroxylase to PTH (in chicks deprived of vitamin D for 1-10 d). These results demonstrate that: under normal metabolic conditions, the normal vitamin D status regulates the activity of 1 alpha-hydroxylase so as to dampen both its "basal" activity and its responsiveness to stimulation by PTH; and vitamin D deprivation insufficient to cause hypocalcemia enhances both the "basal" activity of 1 alpha hydroxylase and its responsiveness to stimulation by PTH. The results suggest that the normal dampening of 1 alpha-hydroxylase and both of the demonstrated enhancements of its activity are mediated by normal and reduced levels of circulating 1,25-(OH)2D, respectively. The finding that PTH fails to further stimulate 1 alpha-hydroxylase when vitamin D deprivation is sufficient in duration to cause hypocalcemia confirms the findings of other investigators and again demonstrates that observations made during abnormal metabolic circumstances may bear little on the physiologic regulation of 1 alpha-hydroxylase under normal or near-normal metabolic circumstances. PMID- 4038408 TI - Presumed Alzheimer's disease beginning at different ages in two twins. PMID- 4038407 TI - Increased glomerular thromboxane synthesis as a possible cause of proteinuria in experimental nephrosis. AB - Altered glomerular metabolism of arachidonic acid (AA) has already been demonstrated in experimental nephrotoxic nephritis. The enhanced synthesis of thromboxane A2 (TxA2) in isolated glomeruli that has been found may mediate changes in renal hemodynamics. The objectives of this investigation were: to check whether glomerular AA metabolism is also altered in a model of glomerulopathy in which no leukocyte infiltration or platelet deposition could be demonstrated; to establish a correlation between the altered AA metabolism and proteinuria; and to explore whether the alteration of the prostaglandin (PG) pathway found in isolated glomeruli is an in vitro artifact or reflects a modification in vivo. We used a model of glomerular damage characterized by heavy and persistent proteinuria, which was induced in the rat by a single intravenous injection of adriamycin. At light microscopy, minimal glomerular abnormalities were found in this model. Electron microscopy showed profound alterations of glomerular epithelial cells with extensive fusion of foot processes and signs of epithelial cell activation. Electron microscopy of numerous glomeruli showed no platelet deposition or macrophage and leukocyte infiltration in this model. Isolated glomeruli from nephrotic rats studied 14 or 30 d after a single intravenous injection of adriamycin (7.5 mg/kg) when animals were heavily proteinuric generated significantly more TxB2, the stable breakdown product of TxA2, than normal glomeruli. No significant changes were found in the other major AA metabolites formed through cyclooxygenase. Urinary excretion of immunoreactive TxB2 was also significantly higher in nephrotic than in normal animals. Administration of a selective Tx synthetase inhibitor, UK-38,485, from day 14 to day 18 after adriamycin resulted in a significant reduction of proteinuria compared with pretreatment values. Glomerular synthesis and urinary excretion of TxB2 were normal during the UK-38,485 treatment. Additional experiments showed that elevated glomerular synthesis and urinary excretion of TxB2 were not a consequence of increased substrate availability. Maximal stimulation of the renin angiotensin axis with furosemide increased glomerular TxB2 synthesis in normal rats, which was significantly lower than in nephrotic animals. Finally, experiments using a unilateral model of adriamycin nephrosis indicated that the enhancement of glomerular TxB2 synthesis is not simply a consequence of the nephrotic syndrome. We conclude that: there is an abnormality of glomerular AA metabolism in nephritic syndrome, which leads to increased TxA2 production; the increased Tx generation correlates with protein excretion and might be responsible for altering the glomerular basement membrane permeability to protein; and the alteration found in isolated glomeruli probably reflects a modification in vivo, in that urinary excretion of immunoreactive TxB2 is also consistently increased in adriamycin nephrosis. PMID- 4038409 TI - Somatomedin-C levels in healthy young and old men: relationship to peak and 24 hour integrated levels of growth hormone. AB - We investigated the relationship between growth hormone secretion and somatomedin levels as a function of age in normal healthy men. There was a substantial decrease with age in somatomedin levels from 0.95 +/- 0.06 (M +/- SEM) units/ml in young (23 to 27 years) men to 0.68 +/- 0.07 in old (58 to 82 years) men. The blood samples were taken throughout a 24-hour period, so it was possible to analyze the data for correlations between average somatomedin levels and various aspects of growth hormone secretion. There was a significant correlation of somatomedin level with the 24-hour integrated growth hormone level, and a nearly significant correlation with the sum of the highest three peaks, but no correlation with the highest nighttime peak or the basal level of growth hormone. These lower blood levels of somatomedin in the aged may be responsible, at least in part, for the catabolic effects on muscle and bone frequently associated with aging. PMID- 4038410 TI - High frequency of natural autoantibodies in normal newborn mice. AB - Spleen cells from 6-day-old nonimmunized BALB/c and BALB.B10 mice were fused with the nonsecreting hybridoma cell line Sp2/0. Three hundred and eighty-four immunoglobulin-secreting hybrids were screened for antibody activity against mouse actin, tubulin, and myosin, and against TNP, peroxidase, renin, DNA, and neurofilaments. At least 24 hybridomas in the collection (6.25%) exhibited antibody activity against this panel of antigens. Ten of these hybrids were cloned, were propagated, and the corresponding monoclonal IgM protein was isolated from ascitic fluids and was further characterized. At least four groups of antibody specificities were identified: 1) one clone reacting with TNP only; 2) one clone reacting with both actin and tubulin; 3) two clones which bound to both TNP and actin; and 4) a fourth group, comprising the six other clones, which all exhibited widespread reactivity and bound to actin, tubulin, myosin, and TNP. These results indicate: 1) B cell clones directed against self antigens are activated in the internal environment and are recovered consequently by somatic cell hybridization; 2) the widespread antibody specificities found for these newborn mouse antibodies are very similar to those previously characterized with human natural antibodies and human monoclonal Ig; and 3) the frequency of B cells binding to cytoskeletal proteins and TNP is very high (at least 6.25%). PMID- 4038411 TI - Asymptomatic carriage of cryptosporidium in the stool of a patient with acquired immunodeficiency syndrome. PMID- 4038412 TI - Intracranial germ cell tumors: pathobiological and immunohistochemical aspects of 70 cases. AB - Seventy cases of histologically verified intracranial germ cell tumor were reviewed: 43 germinomas, 16 immature teratomas, seven mature teratomas, two embryonal carcinomas, one choriocarcinoma, and one yolk sac tumor. The male-to female ratio was 2.6:1. The average age was 19 years in patients with germinoma, 11 years in patients with immature teratoma, and 17 years in patients with mature teratoma. Duration of symptoms averaged 19 months for germinoma, three months for immature teratoma, and 11 months for mature teratoma. Sixty-six lesions were located in the midline. Fifty-eight percent of the germinomas arose anterior to the pineal gland, whereas 29% of the immature and 14% of the mature teratomas were located anteriorly. The histologic appearance of the germinomas was indistinguishable from that of the usual testicular seminoma. The immature teratomas contained tissue from all three germ layers and exhibited morphologic features of fetal tissue. Of 14 immature teratomas, seven contained, in addition, foci of other malignant germ cell elements; thus, there were two teratocarcinomas, two lesions with germinoma and immature teratoma, two lesions with extensive rhabdomyoblastic differentiation in an immature teratoma, and one lesion with both germinoma and embryonal carcinoma in addition to immature teratoma. The seven mature teratomas consisted of fully differentiated epithelial and mesenchymal tissues. In 23 cases, immunoperoxidase stains for human chorionic gonadotropin (HCG), alpha-fetoprotein (AFP), and carcino-embryonic antigen (CEA) revealed patterns which, with minor exceptions, were essentially identical to those found in genital germ cell lesions. Survival was longest for patients with germinomas. In classifying germ cell tumors of the central nervous system, the World Health Organization's (WHO) classification of testicular germ cell tumors is preferable to its present classification of intracranial germ cell tumors. PMID- 4038413 TI - Abnormalities of Purkinje cell arborization in brindled mouse cerebellum. A Golgi study. AB - The cerebellum of the hemizygous brindled mouse (MObr/y), a murine model of Kinky hair disease (KHD) in human beings, was investigated chronologically using the Golgi technique. In 15-day-old MObr/y, Purkinje cells showed considerable changes in their arborization such as perisomatic dendrite-like processes, numerous spine like protrusions from somata and stem dendrites, focal swellings of stem and distal dendrites and generally poor development of dendritic trees. These changes closely resembled those of KHD. Similar changes except for the focal swellings of dendrites, could be found in control mice at day eight but never after day 12. In the MObr/y receiving intraperitoneal injections of cupric chloride (CuCl2) on postnatal (PN) days seven and ten, Purkinje cells appeared similar, if not identical, to those of controls at PN day 15. Focal swellings of dendrites transiently reappeared in treated animals after PN day 23 but spontaneously subsided by day 110. These results suggested that normal arborization of Purkinje cells in MObr/y is at least in part due to delayed maturation, which is correctable by cupric chloride (CuCl2) treatment. The "weeping willow" deformity, which characterizes Purkinje cells in KHD in humans were not observed in MObr/y. Because other neuronal populations, which are known to be deficient in KHD, appeared well preserved in the murine mutant, these dendritic deformities may be secondary to the loss of other neurons. PMID- 4038414 TI - Ultrastructural and morphometric studies of Purkinje cells of brindled mouse after administration of cupric chloride. AB - The mitochondrial and dendritic changes in Purkinje cells, which developed transiently in cupric chloride treated brindled mice, were investigated chronologically with light and electron microscopy. Both changes occurred predominantly in the anterior lobe of the cerebellum. The maximal mitochondrial changes coincided with dendritic changes, suggesting that these alterations were causally related. In the focally swollen dendrites there were disruption of neurotubules, abnormal mitochondria with electron-lucent or electron-dense matrix and large lamellar bodies. Quantitative analysis of the dendritic spine revealed significant differences in the spine area and synaptic length between the brindled mice and normal littermates. PMID- 4038415 TI - Effect of narcotic premedication on scintigraphic evaluation of gallbladder perforation. AB - A case of gallbladder perforation is presented in which a small bile leak was demonstrated by cholescintigraphy while the patient was receiving meperidine, but not after meperidine was discontinued. The scintigrams obtained during meperidine therapy also showed a pattern of bile-duct obstruction. It is suggested that increased biliary pressure secondary to meperidine administration permitted visualization of the leak. Use of narcotic drugs may be a useful pharmacologic intervention in cases of peritonitis due to small or obscure bile leaks. PMID- 4038416 TI - Continuous intraperitoneal infusion of pentobarbital: a model of barbiturate dependence in the rat. AB - The i.p. administration of pentobarbital using an escalating drug-dose schedule for an 11-day period resulted in the establishment of dependence on pentobarbital in male rats. Mean plasma pentobarbital levels were approximately 5 micrograms/ml during the first 3 days of the infusion period. Subsequently, there was observed a dose-responsive increase in plasma pentobarbital levels for the next 5 days, with a decline in pentobarbital levels noted during the final 3 days of the pentobarbital infusion period. Removal of pentobarbital from the infusate resulted in a rapid decline in plasma levels to less than 50% by 8 hr into the drug-free period and to barely detectable levels by 24 hr. This was correlated with a steadily increasing occurrence of withdrawal signs, with a peak occurrence by 7 to 9 hr after initiation of the drug-free period. Spontaneous locomotor activity was significantly greater in pentobarbital-dosed animals during withdrawal than in saline-infused control rats. The i.p. infusion of pentobarbital is a quick and reliable method for the study of barbiturate dependence in the rat. PMID- 4038417 TI - Effect of chronic ethanol administration on arterial baroreceptor function and pressor and depressor responsiveness in rats. AB - The effect of chronic ethanol administration on arterial baroreflexes was investigated in rats. Comparison of the results with those obtained from rats kept on an isocaloric control diet revealed that chronic ethanol had a differential action on baroreflex sensitivity (BS). The BS after evoked graded rises in arterial pressure was inhibited significantly whereas that tested after an evoked fall in arterial pressure was augmented significantly in chronic ethanol rats. These changes in BS were not secondary to changes in blood pressure as resting arterial pressure was similar in both groups. However, the heart rate was slightly, but significantly lower in the ethanol group. Challenging isocaloric control and chronic ethanol rats with an acute dose of 0.5 g/kg of ethanol produced nonsignificant changes in BS when evoked changes in blood pressure were both pressor and depressor. A dose of 3 g/kg of ethanol decreased the BS tested after phenylephrine-evoked rises in pressure in both groups; however, the percentage of inhibition of BS was greater in the isocaloric control group. The pressor responsiveness to phenylephrine was reduced slightly in chronic ethanol-treated rats, in contrast to that evoked by angiotensin II which was augmented slightly as compared to the control group. There was no significant difference in the depressor responsiveness to nitroprusside. After injection of acute doses of 0.5 and 3 g/kg of ethanol, the dose-response curves to phenylephrine were shifted to the right in a dose-related fashion in both groups, whereas the angiotensin II and nitroprusside dose-response curve remained unchanged after 0.5 g/kg of ethanol in both groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4038419 TI - Mini-review. On the possible importance of an intracellular circulation. AB - Since ultrastructural, biophysical and other studies continue to demonstrate that the internum of the cell is highly structured, the question raised and discussed in this review is whether an intracellular circulatory system is essential for the maintenance of active metabolism. Although cytoplasmic streaming is evident in large animal and plant cells, it is argued that it probably occurs in all cells irrespective of size, and is of particular importance in bringing together interacting molecules fast enough for metabolic processes to occur which would otherwise be far too slow if diffusion were the only form of motion. A common intracellular system would suffice for most metabolic processes and would also help to dissipate waste products. Interruption of this internal circulation would result in the inhibition of metabolic functioning, including for example protein turnover, for which evidence is presented to substantiate this hypothesis. PMID- 4038418 TI - Facile synthesis of platelet-activating factor and racemic analogues containing unsaturation in the sn-1-alkyl chain. AB - Platelet-activating factor, 1 (PAF, 1-O-hexadecyl-2-acetyl-sn-glycero-3 phosphocholine), and octadecyl-PAF were synthesized chemically as the racemates. The sn-1-O-alkyl isomers were isolated after treatment of the racemates with phospholipase A2 and subsequent reacetylation of the 1-O-alkyl-2-lyso-sn-glycero 3-phosphocholines released. Analogues of PAF containing unsaturated alkyl moieties at the sn-1 position (2, 4, 5) were synthesized by utilizing the methoxyethoxymethyl protecting group as a novel method for preparing unsaturated alkyl lipids. This procedure provides a facile means for preparing unsaturated either phospholipids of defined structure that may be tritiated to high radiospecific activity for metabolic studies. Unsaturation in the alkyl chain had minimal effect on the bioactivities examined in this study. PMID- 4038420 TI - Salsolinol and dopamine in rat medial basal hypothalamus after chronic ethanol exposure. AB - Endogenous levels of salsolinol and dopamine were measured by a gas chromatography/mass spectrometry (GC/MS) - selected ion monitoring technique using deuterated internal standards in Long Evans rats chronically exposed to ethanol for ten months. Chronic ethanol exposure produced significant increases of dopamine and salsolinol concentrations in the medial basal hypothalamus but not striatum. The data suggest that the occurrence of salsolinol in rat brain tissue is a consequence of an in vivo Pictet-Spengler cyclization. PMID- 4038421 TI - Hepatosplenic peliosis after danazol and glucocorticoids for ITP. PMID- 4038422 TI - The heart in hypertension. PMID- 4038423 TI - Diagnosis of the unstable detrusor: comparison of an incremental and continuous infusion technique. AB - Incremental infusion cystometry and continuous infusion urethrocystometry were performed on sequential days in 52 patients with an unstable detrusor. Bladder compliance was the same in both techniques. However, continuous infusion urethrocystometry demonstrated involuntary detrusor contractions in three times as many patients as incremental infusion cystometry. It is concluded that in the supine position, medium rate continuous infusion urethrocystometry is more discriminating than rapid rate incremental infusion cystometry with a Lewis recording cystometer in the demonstration of involuntary detrusor contractions. PMID- 4038424 TI - The human weaning process. AB - The weaning process in relation to the nutritional adequacy of human lactation is reviewed. Current trends in breast-feeding, both in industrialized countries and the developing world, are considered, as well as associated changes in weaning practices. Consideration is also given to infant growth patterns in the Western world and how these are being influenced by current dietary practices. The nutritional requirements of babies during the first year of life are discussed, and recent concepts indicating that current estimates might be in excess of physiologic needs are introduced. These theories are of fundamental practical importance in terms of defining the length of time that exclusive breast-feeding remains adequate and determining when the introduction of complementary foods becomes necessary on nutritional grounds. It is emphasized that the weaning process is naturally a lengthy one, lasting many months rather than a few weeks, and that the provision of additional foods need not inhibit a mother's capacity for lactation as long as these feeds are administered in the correct fashion. PMID- 4038425 TI - Mycobacterium avium infection in a silicone-injected breast. AB - A case of atypical mycobacterial infection (M. avium intracellulare) in a silicone-injection augmented breast is described. The silicone injection may have been a contributing factor to the development of this unusual infection. Disseminated M. avium was present in this patient, with breast involvement being suggested by the rapid appearance and disappearance of localized areas of erythema and tenderness. Aggressive treatment of these breast infections while they are still localized may prevent systemic spread. Conventional incision and drainage of the breast abscess combined with multidrug treatment directed against M. avium is the recommended therapy. PMID- 4038426 TI - Ascorbic acid and the behavioral response to haloperidol: implications for the action of antipsychotic drugs. AB - Haloperidol, a widely used antipsychotic drug, was tested for its ability to block the behavioral response to amphetamine and to elicit catalepsy in rats treated with saline or ascorbic acid (1000 milligrams per kilogram of body weight). By itself, ascorbic acid failed to exert significant behavioral effects, but it enhanced the antiamphetamine and cataleptogenic effects of haloperidol (0.1 or 0.5 milligrams per kilogram). These results, combined with a growing body of biochemical evidence, suggest that ascorbic acid plays an important role in modulating the behavioral effects of haloperidol and related antipsychotic drugs. PMID- 4038427 TI - Ototoxicity of subcutaneously administered aztreonam in neonatal rats. AB - Aztreonam (SQ 26,776) was given subcutaneously to three groups of neonatal rats at daily doses of 150, 600, and 2400 mg/kg from postnatal Days 10 through 16. Two similar groups given 400 mg of streptomycin kg-1 day-1 or 12 ml of 0.9% sodium chloride kg-1 day-1 on the same schedule served as a positive and negative control group, respectively. On postnatal Days 28 and 56, the neonates were evaluated for level of spontaneous activity and auditory and vestibular function. Half of the neonates in each group were necropsied on postnatal Day 29, and the other half on postnatal Day 57. The inner ears of all neonates were evaluated for histopathologic evidence of ototoxicity. No functional or histopathologic evidence of ototoxicity was found in any neonatal rat dosed with aztreonam or saline. However, neonates given streptomycin were hyperactive, had severely impaired hearing and vestibular function, and had morphologic changes in the sensory nerve endings of the semicircular canals, utriculus, sacculus, and cochlea. The histopathologic evidence of the ototoxic effects of streptomycin correlated highly with the functional data. Thus, under these conditions, aztreonam demonstrated no ototoxic effects in neonatal rats. PMID- 4038428 TI - Tissue characterization by magnetic resonance imaging in hypertrophic cardiomyopathy. PMID- 4038429 TI - Soy protein products and heme iron absorption in humans. AB - Dual radioiron tags were used to measure both heme and nonheme iron absorption simultaneously from meat-containing meals in 76 healthy male volunteers. Partial substitution of beef with soy flour reduced the availability of nonheme iron but improved the percentage absorption of heme iron significantly (27 to 59% rise). In contradistinction three other powerful inhibitors of nonheme iron absorption, bran, tea, and desferrioxamine, had no appreciable effect on heme. Ascorbic acid (100 mg and 1000 mg in separate experiments) improved nonheme iron uptake markedly but also failed to alter the assimilation of heme. These studies demonstrate that the deleterious effects on iron nutrition of substituting soy protein for beef are partially offset by improved availability of the remaining heme iron as well as by an increase in the nonheme iron content of the meal. PMID- 4038430 TI - An acute myeloproliferative disorder characterized by myelofibrosis and blast cells that express phenotypic properties associated with multiple hematopoietic lineages. AB - The authors investigated the blast cells obtained from two patients with acute myelofibrosis with the use of recently developed immunochemical and ultrastructural markers. They intended to examine the expression of megakaryoblastic, erythroblastic, myeloblastic, and monoblastic properties in these cells. Respectively, 20% and 15% of the blasts from patient 1 and patient 2 expressed a megakaryoblastic phenotype as determined by reactivity with a polyclonal platelet glycoprotein antisera (PGP). However, 55% and 73% of these patients' blasts also exhibited myeloid/monocytic properties. Ultrastructural studies clearly demonstrated findings consistent with the presence of myeloblasts, monoblasts, and erythroblasts, as well as undifferentiated agranular blasts. These findings demonstrate the existence of a disorder in which blast cells simultaneously express properties associated with multiple hematopoietic lineages. This disorder is characterized by impaired terminal differentiation. PMID- 4038431 TI - Hepatic encephalopathy associated with extensive portal-hepatic venous shunts: a case report. AB - Extensive intrahepatic portal-hepatic venous anastomosis is very rare. This report describes a 47-year-old man with cirrhosis who presented with mental confusion and flapping tremor, and in whom percutaneous transhepatic portography and superior mesenteric angiography demonstrated shunting between the portal vein branches and the right hepatic vein. Measurements of pressure, ammonia, and immunoreactive insulin in blood of the portal and right hepatic veins clearly indicated that a large amount of portal vein blood was being shunted into the right hepatic vein. These findings suggest that hepatic encephalopathy in this patient is accounted for at least in part by an intrahepatic portal-hepatic venous shunting. PMID- 4038432 TI - Steroid-induced hypersegmentation in neutrophiles. AB - The effect of glucocorticoid administration on the nuclear segmentation of circulating granulocytes was studied in 13 patients with hematologic disorders and in two normal volunteers. In seventeen of eighteen courses, the granulocyte nuclear lobe count increased from 3.24 +/- 0.12 (SD) to 3.41 +/- 0.12 by the third day of treatment (P less than .001). Nuclear segmentation increased even further with continued therapy during a week of observation. Thus, like deficiencies of folate and of vitamin B12, glucocorticoid therapy causes neutrophil hypersegmentation. The cause of this effect is not known. PMID- 4038433 TI - Intravenous gammaglobulin in refractory immune thrombocytopenic purpura: efficacy with or without concomitant steroid therapy. AB - Two patients with immune thrombocytopenic purpura (ITP) refractory to conventional management with steroids and splenectomy were treated with 5-day courses of intravenous gamma globulin (Gamimune-Cutter), 400 mg/kg/day. Improvement was observed in both cases even while steroids were being tapered. In each case when thrombocytopenia subsequently recurred or worsened, further therapy with IV gamma globulin without concomitant steroids was followed by definite increase in platelet numbers. These observations confirm that the Cutter preparation of IV gamma globulin is efficacious in the management of refractory ITP and suggest that in this clinical setting response to IV gamma globulins can occur without concomitant administration of corticosteroids. PMID- 4038434 TI - Treatment of a cyclodialysis cleft with argon laser photocoagulation in a patient with a shallow anterior chamber. AB - A 27-year-old man developed a traumatic cyclodialysis cleft with resulting hypotony. He had a flat peripheral anterior chamber, but the chamber was successfully deepened with the help of a Zeiss four-mirror goniolens, and the cyclodialysis cleft treated with argon laser photocoagulation. PMID- 4038435 TI - Laser trabeculoplasty re-treatment. AB - Because of inadequate control of intraocular pressure, 26 eyes of 24 patients with primary and secondary open-angle glaucoma who had previously undergone argon laser trabeculoplasty were re-treated. Re-treatment was successful in ten eyes (38%); their average decrease in intraocular pressure was 10.2 mm Hg. After laser re-treatment, three eyes (12%) had marked increases in intraocular pressure, ranging from 10 to 37 mm Hg above baseline, necessitating urgent surgical intervention. PMID- 4038437 TI - Microfilaments and the effects of antidiuretic hormone on water permeability. PMID- 4038436 TI - Vascular tumors produced by NIH/3T3 cells transfected with human AIDS Kaposi's sarcoma DNA. AB - Patients with the acquired immunodeficiency syndrome (AIDS) have a high incidence of Kaposi's sarcoma. The etiology, histogenesis, and neoplastic nature of this neoplasm have been controversial. We have therefore searched for transforming gene(s) associated with AIDS Kaposi's sarcoma. DNA from an AIDS patient's Kaposi's sarcoma was transfected into NIH 3T3 cells. Control DNA was derived from human fibroblasts or salmon sperm. Kaposi's sarcoma DNA, but not the control DNA, transforms NIH/3T3 cells with a frequency of approximately 0.02 foci per 5 X 10(5) cells/micrograms DNA. The primary and secondary transfectants contain human repetitive DNA sequences. The transfected clones produced hemorrhagic angiosarcomatous neoplasms when implanted in nude mice. The histology of the nude mouse tumors is very similar to human Kaposi's sarcoma. The tumor produced by some transfectants is highly invasive and metastatic in nude mice. No significant homologues of rasN, rasH, rasK, v-sis, v-src and v-fes oncogenes (known to transform NIH/3T3 cells) were identified in the Kaposi's sarcoma DNA-transformed cells. Thus, AIDS Kaposi's sarcoma DNA may contain a distinct transforming gene(s). PMID- 4038438 TI - Involvement of calcium and cytoskeleton in gallbladder epithelial cell volume regulation. AB - The importance of calcium and cellular cytoskeletal elements in the activation or control of volume regulation by epithelial cells was explored in Necturus gallbladder. Gallbladder cells have been previously shown to rapidly readjust their volumes to control size after osmotic perturbation of the mucosal bathing solution. Removal of calcium from the perfusates caused dramatic morphological changes that prevented assessment of the role of extracellular calcium in volume regulation. The regulatory volume increase (RVI) that follows shrinkage of the cell due to perfusion of a hypertonic mannitol solution is insensitive to agents that interfere with cell calcium- or calmodulin-mediated events (quinidine, trifluoperazine) and is not blocked by agents that cause changes in the cytoskeleton (colchicine, cytochalasin B). Osmotically induced cell swelling is followed by regulatory volume decrease (RVD), which is inhibited by agents that interfere with calcium-dependent processes (quinidine, trifluoperazine) and by the microfilament inhibitor, cytochalasin B. These results indicate that RVD depends on calcium, calmodulin, and an intact microfilament network, whereas RVI is independent of these factors. PMID- 4038439 TI - How laboratory dogs accommodate meals of different size but similar composition. AB - Healthy laboratory dogs appear to absorb a mixed meal from the gut at a constant rate. This rate is apparently not affected by meal size. If this is the case, then duration of absorption should depend on total or integrated meal size, whereas metabolite and hormonal levels would be independent of the number of feedings. To explore these hypotheses further, we compared the metabolite and hormonal responses with a single mixed meal and one divided in two halves, provided in two feedings 4 h apart. We detected no effect of the second meal in the metabolic response levels of glucose, lactate, pyruvate, alanine, free fatty acids, or 3-hydroxybutyrate or the hormonal responses of insulin, pancretic glucagon, gastrin, or secretin. Only minor differences were detectable in the hormonal response levels of pancreatic polypeptide, gastric inhibitory peptide, and enteroglucagon, consistent with a response to a second meal. We conclude that the observed change in circulating metabolite or hormone concentration is independent of the size of meal eaten, but the duration of the excursion depends on meal size. Thus, during the bulk phase of nutrient uptake, the absorption mechanism of the laboratory dog appears to be saturated. PMID- 4038440 TI - Suppression of endotoxin-induced corticosterone secretion in rats by H1 antihistamine. AB - Corticosterone (CS) secretion is stimulated in rats by an intraperitoneal injection of bacterial lipopolysaccharide (LPS) or by subjecting the animals to immobilization stress. LPS injection caused a significant increase in the lung histamine level and a sharp reduction in the number of intact peritoneal mast cells. Injection of compound 48/80, a histamine liberator, provoked an increase in the histamine levels of the blood and lung and a decrease in the number of intact peritoneal mast cells with a concomitant increase in CS secretion. Administration of histamine, at a dose of 10 mg/kg, induced a marked increase in CS release. LPS-induced CS secretion was attenuated by pretreatment with an H1 antihistamine, promethazine (PMZ), whereas an H2-antihistamine, metiamide, had no effect. In contrast, PMZ was ineffective on CS release provoked by immobilization stress. These results suggest that LPS-induced CS release is mediated, in part, by histamine released in the peripheral tissues, whereas an immobilization stress induced increase is not mediated by the amine. PMID- 4038441 TI - Developmental maturation of D-glucose transport by rat jejunal brush-border membrane vesicles. AB - D-Glucose uptake into jejunal brush-border membrane vesicles was studied in suckling (2-wk-old), weanling (3-wk-old), and adolescent (6-wk-old) rats. The purity of the membrane vesicles from all age groups was validated by the finding that the specific activity of brush-border enzyme markers was severalfold greater in membrane vesicles compared with corresponding values in mucosal homogenate. D Glucose uptake was inversely related to increasing medium osmolality, indicating that uptake of D-glucose was into the intravesicular space rather than binding. D Glucose uptake was sodium dependent at all age groups; however, the initial uptake at 20 s was significantly greater in adolescent rats compared with suckling rats. The addition of valinomycin to KCl-preincubated vesicles in the presence of Na+ gradient resulted in a severalfold increase in D-glucose initial uptake over Na+ gradient alone, indicating that D-glucose uptake was electrogenic at all age groups. To delineate the mechanism for the decrease in the initial uptake in suckling rats, two experiments were performed: 1) an exchange tracer study that indicated the activity of D-glucose-Na+ transporters was similar in suckling and adolescent rats, and 2) a study that indicated 22Na uptake, as an indicator for Na+ permeability, was significantly greater in suckling rats compared with adolescent rats. These findings suggest that a Na+-dependent, electrogenic D-glucose uptake is already developed in the suckling period; however, because of the increased permeability to Na+, the Na+ gradient dissipates faster, resulting in a decrease in initial uptake. PMID- 4038442 TI - Concordance for the syndrome of autism in 40 pairs of afflicted twins. AB - The UCLA Registry for Genetic Studies in Autism was established in 1980 to test the hypothesis that genetic factors may be etiologically significant in subsets of patients. To date 61 pairs of twins have enrolled and 40 meet research diagnostic criteria for autism. The authors found a concordance for autism in these 40 pairs of 95.7% in the monozygotic twins (22 of 23) and 23.5% in the dizygotic twins (four of 17). PMID- 4038443 TI - Intrathecal clonidine: analgesia and effect on opiate withdrawal in the rat. AB - Clonidine, an alpha 2 adrenergic agonist, has analgesic properties and recently has been used to suppress opiate withdrawal. These two properties theoretically make it a suitable analgesic substitute in patients tolerant to opioids. The objectives of this study were to see if intrathecal clonidine is analgesic and whether it can modify morphine withdrawal at the spinal level. Rats chronically implanted with catheters in the lumbar subarachnoid space were utilized. In analgesia experiments, intrathecal clonidine produced analgesia with the peak effect in the paw-lick test occurring at 200nM, and in the tail-flick test analgesia was apparent at 100 nM and peaked at 400 nM (in 10 microL Ringer's lactate). In dependency experiments, animals dependent on morphine (300 mg X kg 1) received intrathecal clonidine 25, 50, 200 nM in 10 microliter Ringer's lactate 72 h after morphine. Following this, a naloxone challenge, 3 mg X kg-1 was administered and withdrawal assessed. Clonidine-treated animals showed significant weight loss and decrease in temperature, and those treated with high doses showed marked hypothermia and hind-limb flaccidity. Intrathecal clonidine prevented the hyperalgesia associated with opiate withdrawal but did not affect the occurrence of the majority of behavioral signs (e.g., piloerection, irritability) associated with morphine withdrawal. Intrathecal clonidine prevented the naloxone-induced increase in blood pressure during withdrawal and in animals not treated with morphine-produced hypotension. Thus, intrathecal clonidine is analgesic, and part of the antiwithdrawal action of clonidine may be exerted at the spinal level. PMID- 4038444 TI - [The effect of continuous hyperthermic peritoneal perfusion using high-dose cis diamminedichloroplatinum for peritoneal dissemination of gastric cancers]. AB - A continuous hyperthermic peritoneal perfusion using high-dose cis diamminedichloroplatinum (CDDP) and its antidote, sodium thiosulfate, was applied to eight patients with peritoneal metastasis from gastric cancers. Two of eight patients showed partial response and the rate of decrease of ascites was 38%. Renal failure and leukopenia were observed in one and two patients, respectively, but no severe or lethal dysfunction was observed and all were tolerated. These results showed that CDDP exerted anti-tumor effects on peritoneal metastasis from gastric cancers when used in high doses in combination with hyperthermia. PMID- 4038445 TI - [Cis-dichlorodiammineplatinum (II) in the treatment of a refractory non-Hodgkin's lymphoma with renal involvement]. AB - A case of refractory non-Hodgkin's lymphoma with renal involvement that showed marked response to cis-dichlorodiammineplatinum (II) (CDDP) is reported. It is noteworthy that there was clear dissociation of responses between the renal lesion and extrarenal ones. CDDP is considered to be useful as part of a second line or salvage therapy for refractory non-Hodgkin's lymphoma. PMID- 4038447 TI - [Complete remission of recurrent ovarian dysgerminoma obtained by combined chemotherapy with cisplatin, adriamycin and cyclophosphamide]. AB - Based on the clinical course of ovarian dysgerminoma with multiple metastatic foci in the lung recurring at 7 years and a half after initial therapy, various problems of diagnosis, treatment, and administration of this tumor were discussed. As to the multiple recurrent foci, complete remission was obtained by 3 courses of combined chemotherapy with cisplatin, adriamycin and cyclophosphamide. Generally speaking, this type of tumor is remarkably sensitive to various kinds of oncostatics, and chemotherapy involving the above chemotherapeutic agents is worth trying in selective cases of advanced or recurrent cases. PMID- 4038446 TI - [Effect of cis-platinum in neuroblastoma]. AB - We treated six children with neuroblastomas. They were all refractory to conventional chemotherapy or at an advanced stage when diagnosed. Patients were four males and two females aged 1 to 7 years old, with a mean age of 3.7 years. Total cis-DDP dose ranged from 60 mg/m2 to 720 mg/m2, with a median dose of 240 mg/m2, and a mean dose of 260 mg/m2. Of the six children, two were PR, three were PD, and one was NC. Of three non-responses, two cases were clinically improved. Two cases had renal dysfunction but this improved within 3 weeks. It is said that cis-DDP induces irreversible renal damage, especially tubular necrosis. Our two cases had progressively decreased creatinine clearance, though values of BUN and creatinine were normal. Bone marrow suppression was mild, so there was no need to discontinue or modify the cis-DDP chemotherapy schedules. Two hypo-magnesemia were found, both cases being asymptomatic. Transient liver dysfunction occurred in one child, and nausea and vomiting were observed in almost all cases. PMID- 4038448 TI - [Prophylactic efficacy of timiperone (Tolopelon) in vomiting caused by DDP]. PMID- 4038449 TI - Neonatal lumbar plexus injury. PMID- 4038450 TI - Hearing acuity of children with otitis media with effusion. AB - Hearing levels are reported for a cohort of 222 infants (aged 7 to 24 months) and 540 older children (aged 2 to 12 years) with otitis media with effusion (OME). The infants had an average speech awareness threshold of 24.6 dB hearing level (HL). The older group had mean bone conduction thresholds less than 10 dB HL, and air conduction thresholds averaged 27 dB HL; however, acuity was 7 dB less impaired at 2,000 Hz. The mean three-frequency pure tone average and speech reception threshold were 24.5 and 22.7 dB, respectively. Hearing acuity was not significantly related to age or previous duration of OME. The otoscopic observation of an air-fluid level or bubbles was associated with less hearing impairment; however, a predictive relationship between hearing levels and tympanogram characteristics could not be demonstrated. PMID- 4038451 TI - Benzo[a]pyrene metabolism and DNA adduct formation mediated by English sole liver enzymes. AB - Tritiated benzo[a]pyrene (BaP) and (+/-)-7,8-dihydroBaP (BaP 7,8-dihydrodiol) were incubated with English sole liver microsomes in the presence of salmon testes DNA. The modified deoxynucleosides were isolated by Sephadex LH-20 column chromatography and analyzed by reverse-phase high-pressure liquid chromatography (HPLC). A single, major adduct (60-68% of the total modified deoxynucleosides) was formed when either BaP or BaP 7,8-dihydrodiol was incubated with sole liver microsomes and DNA. Although other minor BaP-DNA adducts were formed, none represented greater than 3% of the total adducts. The major adduct had a retention time on HPLC identical to that of the N2-[10 beta (7 beta, 8 alpha, 9 alpha-trihydroxy-7,8,9,10-tetrahydrobenzo[a]pyrene)yl]-deoxy-guanosine (7R-anti BPDE/trans-dG) adduct formed when anti-BPDE, the ultimate carcinogen of BaP in mammals, was incubated with DNA. Analysis of the Bay region tetrols showed that only the 7 alpha, 8 beta, 9 beta, 10 alpha-tetrahydroxy-7,8,9,10-tetrahydroBaP, a hydrolysis product of the anti-BPDE, was formed when BaP was incubated with sole liver microsomes. When BaP 7,8-dihydrodiol was used as the substrate, the 7 alpha, 8 beta, 9 beta, 10 alpha-, 7 alpha, 8 beta, 9 alpha, 10 beta-, and 7 alpha, 8 beta, 9 alpha, 10 alpha-tetrahydroxy-7,8,9,10-tetrahydroBaP's were formed, indicating the formation of both anti- and syn-BPDE. The ratio of tetrols of anti-BPDE/syn-BPDE was 2; however, the ratio of adducts of anti-BPDE/syn-BPDE was 20. Thus, the findings show that hepatic microsomes of English sole, a fish species having a high incidence of liver neoplasia in chemically contaminated estuaries, metabolized BaP and BaP 7,8-dihydrodiol stereoselectively to form predominantly the 7R-anti-BPDE/trans-dG adduct. PMID- 4038452 TI - Non-invasive estimation by cross sectional echocardiography of myocardial damage in cardiomyopathy. AB - Retrospective and prospective studies of high resolution cross sectional echocardiograms were undertaken in order to establish an ultrasonic method for the non-invasive estimation of degeneration and fibrosis of the endomyocardium in cases of cardiomyopathy. When the echocardiograms of the ventricular wall were compared with the histological specimens intense abnormal echoes were seen at the sites of myocardial degeneration and fibrosis of the ventricular wall. The abnormal echoes classified into five types: types I, II, III-1, III-2, and III-3. Type I and type III-1 echoes were the strongest followed by those of types II and III-2, and then those of type III-3. The intensity of the abnormal echoes was 5 20 decibels stronger than that from intact tissue and was closely related to the consistency and density of the diseased tissue. These findings strongly suggest that the boundary between degeneration or fibrosis and the intact normal myocardium was the source of the abnormal myocardial echoes and that the extent and the pattern of the distribution of the sites of degeneration and fibrosis in the myocardium were reflected in the echo patterns. Thus the tissue characteristics of the sites of degeneration or fibrosis of the myocardium may be determined non-invasively by measuring the echo intensity. PMID- 4038453 TI - Conduction system defects in three perinatal patients with arrhythmia. AB - The cardiac conduction systems of three patients who died in the perinatal period were studied histologically. Rhythm disturbances were observed in these patients immediately before death. The sinus node was notably hypoplastic without increase in fibrous content in all cases. The atrioventricular node was smaller than expected in all, and the entire atrioventricular conduction axis was small in two cases. This study supports the need for a detailed examination of the cardiac conduction system so as to provide a better understanding of the clinicoanatomical relation in the context of fatal perinatal arrhythmias. PMID- 4038455 TI - Fetal umbilical artery flow velocity waveforms and placental resistance: clinical significance. AB - Since the umbilical arteries carry fetal blood to the placenta we studied flow velocity waveforms in these vessels with a simple continuous wave Doppler system to assess placental blood flow. The ratio of peak systolic to least diastolic (A/B) flow velocity was measured as an index of placental flow resistance. In 15 normal pregnancies there was a small but significant decrease in this ratio through the last trimester. The A/B ratio was measured on 436 occasions in 168 high-risk pregnancies. In 32 of 43 fetuses subsequently shown to be small for gestational age there was an increase in placental flow resistance with reduced, absent or even reversed flow in diastole. This finding was also present in the one fetus which died in utero. Serial studies in patients with fetal compromise indicated increasing flow resistance, a reverse of the normal trend. These results were not available to the clinician yet of 24 fetuses born before 32 weeks 13 had a high A/B ratio, and all of them were born electively. Maternal hypertension was associated with an increase in fetal placental flow resistance. The umbilical artery A/B ratio provides a new and non-invasive measure of feto placental blood flow resistance. PMID- 4038454 TI - Retinol and postoperative colorectal cancer patients. AB - In order to determine whether low plasma levels of retinol and its carrier (retinol binding protein) are related to increased risk of cancer recurrence, these were measured in 103 patients who had had colorectal cancer surgically removed. According to the modification of the Dukes' classification, 66 had B2 tumours (with no nodal involvement' and 37 had C tumours (with lymph-node metastases). These patients were part of the Cross Cancer Institute Adjuvant GI Cohorts who were on the control arms receiving no further treatment. At the time of blood sample collection, they were believed to be free of neoplastic disease. The post-operative patients were found to be associated with subnormal circulatory levels of retinol (43.3 micrograms dl-1 vs 65.3 micrograms dl-1) and its carrier protein (4.6 mg dl-1 vs 5.7 mg dl-1), when compared with apparently healthy subjects. The latter being more markedly depressed in patients with "C" type tumour (3.8 mg dl-1) than that in those with "B2" type tumour (5.0 mg dl-1). These findings appeared to be persistent during the follow-up study when a second blood sample was collected, one to four months later from 40 patients. Furthermore, the initial plasma retinol level in conjunction with RBP was found to be even lower in 12 patients (35.1 micrograms dl-1, 3.7 mg dl-1) who subsequently had cancer recurrence than in those who remained free of apparent cancer (44.5 micrograms dl-1, 4.6 mg dl-1). The lowest initial values of retinol (19.3 micrograms; 18.8 micrograms dl-1) and RBP (2.4; 1.6 mg dl-1) recorded in the study were seen in the only two patients who died of the disease at the time of follow-up. PMID- 4038456 TI - A kinetic analysis of hexose transport in cultured human lymphocytes (IM-9). AB - 3-O-Methyl-D-glucose transport across the plasma membrane of cultured human lymphocytes of the IM-9 line was followed for net entry into sugar-free cells (zero trans entry), net exit into sugar-free medium (zero trans exit) and for equilibration of labelled sugar in cells with the same sugar concentration in the intracellular water as in the medium (equilibrium exchange). The measurements were performed at 37 degrees C (pH 7.4). Equilibrium exchange of 1 mM 3-O methylglucose (t 1/2 about 7 S) was exponential, suggesting a homogeneous cell suspension. Initial rates of transport showed a Michaelis-Menten dependency on the sugar concentration. The transport system was found to be asymmetric with the following kinetic parameters. Zero trans entry: Km = 2.8 mM, Vmax = 10.7 mM X min 1. Zero trans exit: Km = 9.5 mM, Vmax = 37.9 mM X min-1. Equilibrium exchange: Km = 9.9 mM, Vmax = 44.0 mM X min-1. Finally, the affinity constant for the internal site was measured as approx. 1.2 mM using the infinite cis protocol. PMID- 4038457 TI - Effect of D-galactosamine in vitro on [U-14C]palmitate oxidation, triacylglycerol synthesis and secretion in isolated hepatocytes. AB - Isolated rat hepatocytes were used to study in vitro effects of 10 mM D galactosamine (GalN) on hepatic fatty acids metabolism. At this concentration, membrane integrity and biochemical competence (i.e., gluconeogenesis and ureogenesis) remained unaffected. Protein synthesis and secretion, as measured by the incorporation of [U-14C]leucine into total and medium protein, was significantly inhibited when incubated for more than 2 h. GalN activated the incorporation of [U-14C]palmitate into triacylglycerols and depressed its utilization in the formation of labelled ketone bodies and 14CO2. Hepatocytes isolated from fasted rats exposed to GalN in vitro did not show any variation in prelabelled triacylglycerol secretion. GalN induced a rapid inhibition of prelabelled triacylglycerol secretion by hepatocytes isolated from fed rats in which this secretion occurred to a larger extent than in hepatocytes isolated from fasted rats. The data reported here suggest that GalN induces a rise of triacylglycerol synthesis by inhibiting the palmitate oxidation pathway and a decrease of triacylglycerol secretion through an early derangement of the secretory pathway. PMID- 4038458 TI - The phospholipids of lamellar body material from fetal rabbit lung tissue in culture. Unusual phosphatidylcholine fatty acid profile. AB - Tissue pieces of rabbit fetal lung, 23 days gestation, were cultured for 7 days in serum-free medium to obtain lamellar body material for phospholipid analysis. Cultures were maintained in culture medium without serum and (1) with no added hormones (control cultures), (2) with thyroxine (1 x 10(-7) M), (3) with cortisol (1 x 10(-7) M) and (4) with thyroxine plus cortisol (1 x 10(-7) M each). The hormonal response was evaluated by measuring the quantity of lamellar body material isolated from the tissue pieces after the 7-day culture period. Compared to control cultures, more lamellar body material was recovered from cultures treated with cortisol (180% of control) and with thyroxine plus cortisol (250% of control). Cultures treated with thyroxine alone yielded the same amount of lamellar body material as the controls. Hormone treatment produced only minor changes in the glycerophospholipid profile of the lamellar body material. A small but significant increase in the percentage of phosphatidylglycerol and a small but significant decrease in phosphatidylinositol were found in lamellar body material from cultures treated with thyroxine and thyroxine plus cortisol. The disaturated phosphatidylcholine content of the lamellar body material from culture was 28% of the total lamellar body phospholipid and was not affected by hormone treatment. This disaturated phosphatidylcholine content was low compared to the disaturated phosphatidylcholine of lamellar body material from adult lung (46%). The low proportion of disaturated phosphatidylcholine was due to the unusual presence of palmitoleic acid (16:1(cis-9)), which was more than one fourth of the total fatty acid of the lamellar body phosphatidylcholine. It is possible that an abnormal delta 9 fatty acid desaturation activity was expressed in the lung tissue in vitro, which resulted in the high incorporation of the 16:1 fatty acid into lamellar body phosphatidylcholine. PMID- 4038459 TI - Liposomal membranes. XX. Autoxidation of unsaturated fatty acids in liposomal membranes. AB - Autoxidation of egg phosphatidylcholines and polyunsaturated fatty acids, arachidonic and linoleic acids, has been investigated in homogeneous and liposomal membrane systems. In order to monitor the very initial stage of the radical chain mechanism of the autoxidation, an improved method using 1,1 diphenyl-2-picrylhydrazyl radical was newly implemented and used with the regular thiobarbituric acid test to determine the peroxides of polyunsaturated fatty acids. Autoxidation of polyunsaturated fatty acids or lipids was significantly enhanced in liposomal bilayers compared to that in a bulk homogeneous solution. In liposomal bilayers, the reaction could be controlled by membrane fluidity, which was confirmed by the fluorescence polarization technique using 1,6 diphenylhexatriene and dansylhexadecylamine. Even vitamin E esters such as the acetate and the pivalate could depress effectively the autoxidation of egg phosphatidylcholines in bilayer systems, which supported Lucy's proposal (Diplock, A.T. and Lucy, J.A. (1973) FEBS Lett. 29, 205-210) about the importance of the side-chain of vitamin E as an antioxidant. PMID- 4038460 TI - Lysophosphatidylcholine acyltransferase and lysophosphatidylcholine: lysophosphatidylcholine acyltransferase in alveolar type II cells from fetal rat lung. AB - The specific activity of lysophosphatidylcholine acyltransferase in sonicated fetal rat lung type II cells was found to be an order of magnitude greater than that of lysophosphatidylcholine:lysophosphatidylcholine acyltransferase. The specific activity of lysophosphatidylcholine acyltransferase in sonicated fetal rat lung type II cells increases towards the end of gestation, whereas that of lysophosphatidylcholine:lysophosphatidylcholine acyltransferase does not show a change. While lysophosphatidylcholine acyltransferase in whole fetal lung homogenate is more active towards oleoyl-CoA than towards palmitoyl-CoA, the enzyme in sonicated fetal type II cells is more active towards palmitoyl-CoA. If measured with palmitoyl-CoA as acyl donor, the specific activity of lysophosphatidylcholine acyltransferase in type II cells is higher than that in whole lung during late gestation. In contrast, the specific activity of lysophosphatidylcholine:lysophosphatidylcholine acyltransferase in type II cells is lower than that in whole lung. These observations indicate that in fetal rat type II cells the deacylation-reacylation cycle is more important for the formation of dipalmitoylphosphatidylcholine than the deacylation-transacylation process. PMID- 4038461 TI - Antibodies to 5 M urea soluble chromosomal proteins from HeLa cells. AB - The tissue specificity of a chromosomal protein fraction, extractable from chromatin with 5 M urea at low ionic strength, has been examined in HeLa, A549 and HT 29 cells. Electrophoresis in polyacrylamide gels indicates that each cell type has a different content of 5 M urea soluble proteins which are distinguishable from the histones, from the tight DNA-binding proteins and from the high-mobility-group chromosomal proteins. Antibodies against 5 M urea soluble proteins extracted from HeLa cells were produced in mice. Although each of the mice tested prior to immunization contained a detectable amount of antibodies against both the 5 M urea soluble proteins and tight DNA-binding proteins, immunization elevated the level of the antibodies in the serum over 100-fold. The antibodies do not distinguish between the 5 M urea extracts obtained from different sources because most of the antibodies are directed against antigens shared by the cells studied. Immunofluorescence studies reveal that components which cross-react with 5 M urea soluble chromosomal proteins are also present in the cytoplasm. We conclude the following. (1) 5 M urea extracts from chromatin a group of proteins which differs among cells. (2) Mice contain detectable amounts of autoantibodies against these chromosomal proteins. (3) Immunization with the 5 M urea extractable fraction elicits antibodies against a restricted number of antigenic components which are shared among the cells studied. (4) 5 M urea extractable proteins are found both in the nucleus and cytoplasm; part of these may be cytoskeletal elements. Because the antisera do not react with histones, high-mobility-group proteins and tight DNA-binding proteins, they may be used for various functional studies on the 5 M urea extractable chromosomal protein fraction. PMID- 4038462 TI - Microtubule-associated adenylate cyclase. AB - Twice-cycled bovine brain or rat brain microtubule protein contains an adenylate cyclase activity that passes 0.2 micron filters, is activated 2-7-fold by 30 microM forskolin, shows modest stimulation by fluoride (especially in the presence of added AI3+), but is virtually insensitive to added guanine nucleotides. The activity is insensitive to various hormones or Ca2+/calmodulin. The adenylate cyclase is active with both Mg2+ and Mn2+ but activity is less in the presence of Mg2+ than with Mn2+. The cyclase is inhibited by agonists of the adenosine P site. It is proposed that the catalytic unit of adenylate cyclase and probably small quantities of the guanine nucleotide regulatory protein, Ns, are cycled along with microtubules. PMID- 4038463 TI - [Effect of the age of animals on disorders of the contractile function of the heart muscle under stress]. AB - During intensive growth of animals, the main parameters of myocardial contractility were reduced. Poststressor depression of the contraction of isolated papillary muscles was more marked in adult than in young animals. Thus, aging of animals was accompanied by reduced cardiac muscle contraction. It is inferred that strong stress influence might result in a deep depression of the cardiac function in question, threatening the physiological possibilities of adaptation. PMID- 4038464 TI - [Effect of 3-hydroxypyridine derivatives on the central nervous system]. AB - Experiments on mice and rats were made to study the effect of inhibitors antioxidants (3-hydroxypyridine derivatives) on the central nervous system. It was established that 3-hydroxypyridine derivatives (50 to 200 mg/kg) possess a broad spectrum of psychotropic effects. They cause normalization of behavior in conflict situations, exert an antiaggressive and anticonvulsant action (antagonism with corazol), are capable of potentiating the hypnotic effect of barbiturates, and of suppressing the animals' motor activity if given in high doses. Most compounds under study have antihypoxic and antiamnestic effects. PMID- 4038465 TI - [Characteristics of the mechanism of action of complex copper (II) compounds with alpha-amino acids]. AB - There was no direct inhibition of DNA synthesis in ascites hepatoma 22A cells after intraperitoneal injection of single doses of copper (II) complexes with amino acids into tumor-bearing C3HA mice. Meanwhile cis-dichlorodiamine platinum (II) (DDP) as well as sarcolysine showed such inhibition. Copper (II) complexes with alpha-amino acids displayed as significant superoxide dismutase-like activity at concentrations corresponding to therapeutic doses of these compounds. The complexes of copper (II) combined with DDP give an additive antitumor effect in solid tumors of mice. PMID- 4038466 TI - Variations in rates of cesarean section. PMID- 4038467 TI - Histopathologic classification of uterine choriocarcinoma. AB - Histopathologic features of uterine choriocarcinoma were studied to establish new criteria for grading malignancy of the disease. Thirteen items of histopathologic findings concerning the degree of differentiation and the forms of masses of trophoblasts (Trs), the manner of Tr invasion, and host response of surrounding tissues were studied with relationship to prognosis in 70 patients with uterine lesions (alive, 49; dead, 21). Chi-square test results were examined for each item in relation to prognosis of the patients. Four items were thought to have significance and were selected as criteria: (1) island formation; (2) massive proliferation of intermediate-type Trs; (3) rectangular infiltration of Trs to surrounding muscle fibers; and (4) atypia of Trs at the end-point of tumor invasion. A discriminant analysis was carried out (under the standardization of tumor extension and the historical staging of treatment). From the results obtained in discriminant analysis, scores were given to the four items that existed in the specimen. New criteria for grading malignancy are proposed based on scoring these four items. The algebraic sum of the scores had a possible range of +4 to -16. Patients with scores of -9 and above had a low-grade malignancy with a mortality rate of 7%. Patients with scores of -10 and lower had a mortality of 69% and were classified as having tumors of high-grade malignancy. PMID- 4038468 TI - High-dose cisplatin in patients with advanced malignancies. AB - A study was conducted to determine if cisplatin (CDDP) can be given at higher doses than usual, utilizing aggressive supportive measures. Twelve patients were entered into three dose levels of CDDP: level I, 180 mg/m2 given as a short infusion; level II, 220 mg/m2 also given as a short infusion; level III, 200 mg/m2 divided in five daily doses, each infused over 6 hours. In all cases, CDDP was dissolved and given in 250 ml of a 5% saline solution. For levels I and II, intravenous hydration with 200 to 250 ml/hour D5 1/2NS with potassium and magnesium supplements, was started 24 hours before therapy and continued for 3 to 4 days after, longer if nausea persisted. Mannitol was given before (25% solution, 50 ml bolus) and after (20% solution, 500 ml over 3 hours) CDDP. At level III hydration with the same intravenous (IV) fluids was begun the day before therapy and continued without interruption at 200 to 250 ml/hour for a minimum of 24 hours after the completion of the 5 days of chemotherapy. Each daily dose of CDDP was preceded by injection of mannitol (25% solution, 50 ml bolus) and accompanied by a 6-hour infusion of 1000 ml 20% mannitol. Three patients received five CDDP courses at level I; 4 patients, seven courses at level II; and 5 patients, seven courses at level III. Ototoxicity was dose limiting in three patients at level II. Transient elevation of serum creatinine was seen following two courses at level I and two courses at level II. The renal impairment was asymptomatic in all cases; dialysis was not needed. At level II, leukocyte nadir counts between 1.0 and 2.0 X 10(3)/mm3 were seen following two courses and between 2.0 and 3.0 X 10(3)/mm3 following three courses. Platelet nadir counts below 50 X 10(3)/mm3 were recorded after four courses and between 50 and 100 X 10(3)/mm3 after one course. Nausea and vomiting occurred frequently, but were tolerable. At level III, myelosuppression was dose-limiting. Nadir leukocyte counts between 1.0 and 2.0 X 10(3)/mm3 followed four courses and between 2.0 and 3.0 followed one course. Nadir platelet counts below 50 X 10(3)/mm3 were seen after three courses; two patients required prophylactic platelet transfusions. Nadirs between 50 and 100 X 10(3) platelets/mm3 followed three further courses. Ototoxicity and nephrotoxicity did not occur at level III.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 4038469 TI - Improved complete response rate and survival in advanced head and neck cancer after three-course induction therapy with 120-hour 5-FU infusion and cisplatin. AB - In a series of three consecutive pilot studies carried out between 1977 and 1981 at Wayne State University, Detroit, Michigan, designed to test the feasibility of multimodality therapy in patients with previously untreated advanced squamous cell carcinoma of the head and neck, patients received three different induction chemotherapy regimens: cisplatin + Oncovin (vincristine) + bleomycin (COB) for two courses; 96-hour 5-fluorouracil (5-FU) infusion and cisplatin for two courses, or 120-hour 5-FU infusion + cisplatin for three courses. Over-all response rates (complete response + partial response) to each of the three induction chemotherapy regimens were high: 80%, 88%, and 93%, respectively. Superior complete response rate in the group receiving three courses of 120-hour 5-FU infusion + cisplatin was 54% versus 29% for COB and 19% for two-course 96 hour 5-FU infusion + cisplatin (P = 0.04). Significant survival advantage at 18 months minimum follow-up for the group receiving three courses of 120-hour 5-FU + cisplatin induction therapy was found. Actual T and N stage may influence the clinical complete response rate. Responders to initial chemotherapy have significantly better survival as compared to nonresponders regardless of subsequent surgery and/or radiotherapy. These studies show that a multimodality approach to management of advanced head and neck cancer is feasible. Superior complete response rate and survival in one of the treatment groups suggest that choice of induction chemotherapy regimens and/or number of courses is of prime importance in such multimodality treatment programs. PMID- 4038470 TI - Role of ligand exchange processes in the reaction kinetics of the antitumor drug cis-diamminedichloroplatinum(II) with its targets. AB - The kinetics of a model reaction between the antitumor drug cis diamminedichloroplatinum(II)(cis-DDP) and the signal nucleotide diadenosine 5',5"'-P1,P4-tetraphosphate (Ap4A) has been investigated by spectrophotometry. The formation of the reactive platinum aquated species was first analyzed by potentiometry using a chloride-specific electrode. Both equilibrium and rate constants were measured. The rate constants for the release of the first and second chloride were found 1.1 +/- 0.5 (S.D.) X 10(-4) and 4.2 +/- 0.2 X 10(-5) sec-1, respectively, at 37 degrees. It was shown that anions such as acetate, phosphate, and pyrophosphate were able, in some conditions, to exchange with chloride to form acetato, phosphato, or pyrophosphato complexes. The reaction of cis-DDP with Ap4A or other targets involves at least four steps, which have been analyzed separately. The values of rate constants deduced from the analysis of the overall reaction are in agreement with those determined independently from the separated steps. The second-order rate constants for the reaction of acetato, phosphato, and pyrophosphato complexes with Ap4A (0.2 +/- 0.02, 0.20 +/- 0.02, and 0.16 +/- 0.03 M-1 sec-1, respectively) are close to that of monoaqua monochloro (0.16 +/- 0.1 M-1 sec-1) and lower than that of the diaqua species (0.94 +/- 0.06 M-1 sec-1). At a high concentration of Ap4A, the reaction kinetics is slowed down. The formation of a complex of cis-platinum with the Ap4A phosphate groups is suggested. The intracellular concentration of phosphates, pyrophosphates, and carboxylates is large enough to displace chloride from cis DDP. Inside cells, therefore, ligand exchange processes have to be taken into account to analyze the in vivo reactivity of cis-DDP with its potential targets. PMID- 4038471 TI - Treatment of metastatic colorectal carcinoma with cisplatin and 5-FU. AB - Twenty patients with measurable metastatic colorectal carcinoma were treated every 3 weeks with cisplatin (100 mg/m2 iv) on Day 1 and 5-FU (1000 mg/m2/day by iv infusion over 24 hours) on Days 1-5. Seven patients were previously treated with chemotherapy. The mean performance status for all of the patients was 1.5 (Eastern Cooperative Oncology Group). None of the patients had an objective response to the chemotherapy; 11 patients had stable disease and nine had no response. This study demonstrates that the combination of cisplatin and 5-FU, administered at this dose and schedule, has minimal activity in patients with metastatic colorectal cancer. PMID- 4038472 TI - Time dependency in plasmatic protein binding of cisplatin. AB - The rate of cisplatin binding on proteins was measured in plasma collected from the same patients at several different times of the day. Statistical analysis showed that binding on plasma followed a circadian rhythm with the acrophase occurring around 4 PM. The amplitude of the apparent circadian variation of the binding depends on each patient (mean value, 11%). The binding capacity of plasma was also found to be time-dependent when the patients were prehydrated. The existence of a circadian rhythm in total protein concentration of the plasma could explain the observed results. Since cisplatin is bound more quickly on proteins in the afternoon, the circulating levels of free cisplatin must be lower when the injection is given at this time of day and this may partly explain the reduction in nephrotoxicity for some patients when cisplatin is injected in the afternoon. PMID- 4038473 TI - Disappearance and reappearance of resident macrophages: importance in C. parvum induced tumoricidal activity. AB - We have investigated the role of resident macrophages in the early tumoricidal response to C. parvum. The bacteria were labeled with FITC and resident cells were labeled in situ with blue fluorescent covaspheres to enable subsequent monitoring of cellular changes by flow cytometry. Macrophages disappeared within 5 hr of administration of bacteria. At 24 hr, fibrinous adhesions containing double labeled macrophages were observed at numerous sites on the peritoneum. Macrophages associated with large numbers of bacteria, levels of beads similar to control animals, and elevated plasminogen activator-like activity did not reappear in washings in significant numbers until 72 hr. Thus, the large bacteria containing cells that account for the majority of the early tumoricidal activity are likely to be derived from resident macrophages. PMID- 4038474 TI - Formation of DNA adducts in vivo in rat liver and intestinal epithelium after administration of the carcinogen 3,2'-dimethyl-4-aminobiphenyl and its hydroxamic acid. AB - Administration of the 3H-labeled colon carcinogen, 3,2'-dimethyl-4-aminobiphenyl (DMABP) and its hydroxamic acid derivative, N-hydroxy-N-acetyl-DMABP, to male F344 rats resulted in high levels of covalent binding to hepatic and intestinal DNA, RNA and protein. For both compounds, binding to hepatic macromolecules was 2 4 times higher than in the intestine. High pressure liquid chromatographic analysis of the enzymatically hydrolyzed DNA from liver and intestinal epithelium indicated the presence of two carcinogen-DNA adducts: 5-(deoxyguanosin-N2-yl) DMABP (15%), N-(deoxyguanosin-8-yl)-DMABP (50%), and a decomposition product of the latter (15%). N-acetylated adducts were not detected. When measured after 7 days, all adducts in the intestinal DNA had decreased by 70%, while only a 29% decrease had occurred in the hepatic DNA. To determine if the loss of DMABP products was a consequence of cell turnover or repair, rats were treated with [3H]thymidine and DMABP, and the specific activity of hepatic liver and intestinal DNA was measured. Between 1 and 7 days only a slight decrease in [3H]thymidine content occurred in hepatic DNA as compared with a 95% reduction in intestinal DNA. Thus, the higher rate of DNA synthesis in the intestine versus that in the liver may serve to promote fixation of the initiating lesion and account for the preferential induction of intestinal cancer by DMABP. Furthermore, comparison of these data with metabolic activation pathways reported earlier strongly suggest that N-hydroxy-DMABP is the proximate carcinogenic metabolite of both DMABP and N-hydroxy-N-acetyl-DMABP. PMID- 4038475 TI - Association between DNA strand breaks and specific DNA adducts in murine hepatocytes following in vivo and in vitro exposure to N-hydroxy-2 acetylaminofluorene and N-acetoxy-2-acetylaminofluorene. AB - N-hydroxy-2-acetylaminofluorene (N-OH-AAF) and N-acetoxy-2-acetylaminofluorene (N OAc-AAF) have previously been shown to induce dose-dependent DNA strand breaks in primary hepatocytes from mice and rats. In an attempt to determine the relationship between the extent of DNA strand breaks and the formation of specific DNA-carcinogen bound adducts in murine liver, the capability of N-OH-AAF and N-OAc-AAF to induce both DNA single strand breaks and adduct formation in in vivo and in primary hepatocytes was measured. N-OH-AAF induced a low level of DNA damage in F344 rats (10 mg/kg, i.p.) and in B6 mice (40 mg/kg, i.p.) 4 h after treatment. The DNA adducts identified in vivo were N-(guanin-8-yl)-2 acetylaminofluorene (Gua-C8-AAF) 55% versus 11%, N-(guanin-8-yl)-2-aminofluorene (Gua-C8-AF) 34% versus 67% and 3-(guanin-N2-yl)-2-acetylaminofluorene (Gua-N2 AAF) 11% versus 10%, respectively, for rat and mouse liver. An additional unknown adduct (12%) was detected in mouse liver. Dose dependent DNA binding and formation of individual DNA adducts were observed in rat and mouse primary hepatocytes following 1 h exposure to [ring-3H]-N-OH-AAF (0.1-20 microM) and [ring-3H]-N-OAc-AAF (5-20 microM). The patterns of DNA adducts in mouse and rat primary hepatocytes exposed to N-OH-AAF and N-OAc-AF were similar to those obtained in liver following in vivo treatment with N-OH-AAF. The deacetylase inhibitor, paraoxon (10(-4) M) completely inhibited DNA damage induced by N-OH AAF in mouse and partially in rat hepatocytes while DNA damage caused by N-OAc AAF was only partially inhibited by paraoxon (10(-4) M) in both species. Parallel experiments showed that paraoxon, at low concentration (10(-6) M), did not alter either the level of DNA binding or the pattern of adduct formation in rat hepatocytes treated with N-OH-AAF (20 microM). However, at 10(-4) M paraoxon partially blocked DNA binding (60%) and the formation of Gua-C8-AAF (95%) and Gua N2-AAF (80%) while Gua-C8-AF was increased two-fold. In mouse hepatocytes paraoxon pretreatment (10(-4) M) inhibited the formation of Gua-C8-AF by 70% following exposure to N-OH-AAF (20 microM). Gua-C8-AAF and Gua-N2-AAF were also inhibited but only at 10(-4) M paraoxon.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 4038476 TI - Intravenous and standard immune serum globulin preparations interfere with uptake of 125I-C3 onto sensitized erythrocytes and inhibit hemolytic complement activity. AB - Antibody-sensitized sheep erythrocytes were used as a model to determine the effects of therapeutic immune serum globulin (ISG) preparations on the ability of this particulate activator to fix C3 and initiate hemolysis. Both standard and intravenous forms of ISG inhibit uptake of 125I-C3, presumably by competing for the deposition of "nascent" C3b molecules onto the erythrocytes. Both forms of ISG also inhibit hemolytic activity of whole serum or purified complement components. The inhibition appears to be a specific property of IgG itself, since similar inhibition was not caused by equivalent concentrations of human serum albumin, and was not affected by the buffer in which the ISG was dissolved. Interference with C3 uptake onto antibody-sensitized platelets and/or inhibition of hemolytic complement activity could contribute to the efficacy of high dose intravenous ISG in idiopathic thrombocytopenic purpura. PMID- 4038477 TI - Incidence of hyperbilirubinemia in breast- vs. formula-fed infants. AB - A retrospective study of 233 consecutively born full-term infants was performed to determine the effect of several variables on the development of hyperbilirubinemia. Thirty-five (15%) of the infants developed peak bilirubin levels greater than 12 mg/dl in the first week of life. Step-wise multiple regression analysis revealed that breast-feeding was the most predictive of a group of eight variables for the development of hyperbilirubinemia greater than 12 mg/dl. The correlation between type of feeding and hyperbilirubinemia was significant (p less than 0.02). None of the other factors evaluated was significantly associated with hyperbilirubinemia. Breast-fed infants also were found to have a significantly higher incidence of hyperbilirubinemia greater than 15 mg/dl; 12 of 101 (12%) infants compared with 2 of 117 (2%) formula-fed infants (p less than 0.002). This group of infants accounted for the increased incidence of hyperbilirubinemia greater than 12 mg/dl in breast-fed infants. There was no significant correlation between weight loss and development of hyperbilirubinemia in the breast-fed infants. PMID- 4038478 TI - Some biochemical properties of swine uterus carnosinase. AB - Carnosinase of swine uterus reacts strongly to Mn2+ ions with an increase of the activity: in the presence of 0.25 MnCl2 the activity increases over 5-fold, while at 1 and 2 mM--the increase is 8- and 10-fold respectively. The enzyme is characterized by low stability during storage, especially in the presence of manganese ions. Kinetic properties of uterus carnosinase change depending on a phase of the oestrous cycle of the sow. In the peak luteal phase (5th-13th day of the cycle) Km values were twice as high as in the follicular phase (zero day- beginning of the rut, and 19th day--preoestrus). Two molecular forms of carnosinase were found in the extracts from uterus in the luteal phase of the oestrous cycle, analysed with the method of Sephadex G-100 gel filtration. These were A and B forms, with predominating content of the latter form. This form was characterised by a 2-fold higher Km value compared to the form A. PMID- 4038479 TI - Sigmoid diverticulitis in identical twins. AB - Severe sigmoid diverticulitis requiring left colon resection occurred in monozygotic twins during their third decade. An inherited tendency is suggested. PMID- 4038480 TI - Evaluation of cisplatin-lithium interaction. PMID- 4038481 TI - [Are 2 tablets of magaldrate at bedtime effective in the therapy of duodenal ulcer?]. PMID- 4038482 TI - [Non-puerperal mastitis. Etiology, clinical aspects and therapy]. AB - Non-puerperal mastitis was diagnosed in 79 patients (aged 12-77 years) over the years 1974-1984. Malignant neoplasm was not present. Bacterial infection in the region of the areola was the most frequent finding (40%), followed by abacterial inflammation without involvement of the nipples (29%). The other cases, bacterial or nonbacterial, occurred at different sites. The histological picture or clinical features of an increased secretory activity of the mammary gland (galactorrhoea, mastodynia) in addition to the mastitis was noted in 54 women. Causative organisms were proven in 53% of cases: Staph. aureus (41%) and coagulase-negative staphylococcus (41%), or anaerobic organisms (11%). Physical measures, antibiotics and bromocriptine were used as treatment. At the onset of treatment abscesses were already present or developed in 34 instances. In 28 cases one to six recurrences set in after the end of the treatment period. In 22 patients treated with bromocriptine prophylactically there were only two recurrences. In the majority of patients an increased alveolar secretion was important in the pathogenesis of the bacterial or abacterial inflammation. Prolactin-lowering treatment seems reasonable by itself in cases of abacterial mastitis, or in combination with antibiotics in bacterial mastitis. Recurrences can be prevented by long-term lowering of the peripheral prolactin level. PMID- 4038483 TI - Evidence that central epinephrine neurons participate in the control and regulation of neuroendocrine events during the estrous cycle. AB - Although evidence has shown that central epinephrine (E) neurons play an essential role in the control of preovulatory gonadotropoin surge in rats, their function and site(s) of action are unknown. These experiments were performed in an attempt to identify any changes in E concentration or activity that might take place in areas of the brain known to receive adrenergic axon terminals and to be associated with increased output of gonadotropins (LH, FSH, and PRL) during the estrous cycle. E concentrations were measured by radioenzymatic assay, and E activity was assessed by the linear rate of decline of E (RDE) which occurs 2 h after administration of the centrally active E synthesis inhibitor, SKF 64139. During the proestrous critical period (1500-1700 h), significant increases in both concentration and RDE occurred in the medial preoptic area (mPOA) accompanied by a smaller but significant increase in the RDE in the mediobasal hypothalamus (MBH); 4 h later (2100-2300 h), significant increases in both concentration and RDE were seen in the MBH. At estrus, although E concentrations were generally higher in both the mPOA and MBH than on other days of the cycle, the concentration and RDE in the MBH increased significantly between 1500-1700 h, while RDE in the mPOA increased again between 1700-1900 h. There were no significant changes in either E concentration or RDE in the mPOA or MBH at metestrus or diestrus or in the perifornical area at any of the times studied. Thus, these findings may be associated with the output of gonadotropins over the periovulatory period. PMID- 4038484 TI - Suppressive effect of inflammation and other forms of stress on the binding of prolactin by rat liver. AB - We have found that in female rats a variety of stressful stimuli, including sc inflammation, skin incision, endotoxin injection, and cold exposure, cause a significant decrease (30-86%) in the capacity of the hepatic cell membranes to specifically bind [125I]ovine PRL. Stress-induced decrease in food intake was not a factor in these studies, as nourishment was given only by tube feeding. Neither sc inflammation nor cold exposure affected hepatic binding of [125I]insulin. Further, the induction of inflammation in lactating rats and rats bearing 7,12 dimethylbenz[a]anthracene-induced mammary carcinomas did not affect the binding of PRL by the lactating or malignant mammary tissue. The suppressive effect of inflammation on hepatic binding of PRL was demonstrable in adrenalectomized ovariectomized rats, in hypophysectomized rats receiving hormone replacement, and in adrenalectomized rats that had undergone partial chemical sympathectomy. We conclude that sc inflammation, as well as other forms of stress, decreases hepatic binding of PRL, but does not affect hepatic binding of insulin or mammary binding of PRL. The decrease in hepatic PRL binding is not mediated by a hormone secreted by the adrenals, ovaries, or pituitary, or by catecholamines, but could be mediated by another plasma factor or by peripheral dopaminergic neurons. Stress-induced decrease in hepatic PRL binding, or a related decrease in the binding of other polypeptide hormones, could play a role in the physiological response to stress. PMID- 4038485 TI - The effect of s-triazine-type pesticides and chlorinated hydrocarbons on lactate dehydrogenase. AB - The effect of pesticides on nontarget organisms was studied by following their effect on enzymes from these organisms in vitro. s-Triazines substituted in positions 2, 4, and 6 behaved as inhibitors of plant and animal lactate dehydrogenase, acting competitively with respect to the coenzyme. The inhibition constants were of the order of 10(-3) M and the structure of the substituents exerted no pronounced effect on the inhibition type and the value of the inhibition constant. Polycyclic chlorinated hydrocarbons were found to be much stronger inhibitors, with inhibition constants of the order of 10(-5) M. These substances inhibit the reaction catalyzed by lactate dehydrogenase not only by reaction with the enzyme, but also by a probable direct reaction with the coenzyme. PMID- 4038486 TI - Decrease of fatty acid oxidation, ketogenesis and gluconeogenesis in isolated perfused rat liver by phenylalkyl oxirane carboxylate (B 807-27) due to inhibition of CPT I (EC 2.3.1.21). AB - Sodium 2-[5-(4-chlorophenyl)-pentyl]-oxirane-2-carboxylate (B 807-27 or POCA) inhibits ketogenesis from endogenous and exogenous long-chain fatty acids and 14CO2 production from [U-14 C]palmitate, but not from [U-14 C]palmitoylcarnitine or octanoate, and inhibits gluconeogenesis from lactate and pyruvate in perfused livers of starved rats. Inhibition of ketogenesis, 14CO2 production and gluconeogenesis was complete at concentrations of 10 mumol/l POCA, but onset was more rapid for inhibition of ketogenesis and CO2 production than for gluconeogenesis. Infusion of octanoate abolished inhibition of all three processes. Experiments with isolated rat liver mitochondria showed that carnitine palmitoyltransferase I (EC 2.3.1.21) is inhibited by POCA-CoA. The inhibitory process is dependent on time and concentration, and more pronounced in mitochondria from fed than from fasted rats. Concentrations required for 50% inhibition after 20 min preincubation with POCA-CoA are 0.02, 0.06 and 0.1 mumol/l in liver mitochondria from fed, 24-h-fasted and 48-h-fasted rats, respectively. The inhibitor appears to be tightly bound to the enzyme. The extent of inhibition of carnitine palmitoyltransferase I correlates well with the hypoglycaemic and hypoketonaemic effects of the compounds in fasted rats. We conclude that specific inhibition of the enzyme leads, due to inhibition of long chain fatty acid utilization, to depressed ketogenesis and gluconeogenesis and, in consequence, to hypoglycaemic and hypoketonaemia in vivo under gluconeogenic and ketogenic conditions. PMID- 4038487 TI - Asymmetry of retinal lesions in experimental scrapie after intracerebral inoculation of hamsters. AB - Hamsters injected into the right cerebral hemisphere with the scrapie agent developed retinal lesions to a greater extent in the contralateral than in the ipsilateral eye. This asymmetry was evident during the incubation period as well as during the clinical encephalopathy. The results explain much of the variation in the degree of retinal disease seen earlier at specific times after inoculation. Moreover, they strengthen the hypothesis that scrapie spreads via neurons. PMID- 4038488 TI - Trypanosoma brucei gambiense: growth in vitro of bloodstream forms inhibited by dichlorodiammineplatinum (II) compounds and hypolipidemic drugs. AB - Infectious bloodstream forms of Trypanosoma brucei gambiense were grown in microcultures of murine bone marrow cells in 96-well tissue culture plates. Limiting dilution studies showed that fewer than 10 cultured trypanosomes developed into populations of about 5 X 10(4) parasites per well in a week. Bloodstream parasites were reisolated with high efficiency from mice infected with cultured parasites; fewer than 10 bloodstream parasites successfully established a trypanosome population in a microculture. Both the cis and trans isomers of dichlorodiammineplatinum (II) (cisplatin and transplatin) and a hypolipidemic agent, Wy 14643, were found to have activity against T. b. gambiense growing in microcultures. The minimum concentration of drug necessary to completely eliminate parasites from microcultures was 4 microM for cisplatin, 40 microM for transplatin, and 500 microM for Wy 14643. A preformed complex of cisplatin and bovine serum albumin and another hypolipidemic agent, chlofibric acid, were inactive. This culture system should be useful for rapid screening of large numbers of compounds for trypanocidal activity. PMID- 4038489 TI - Determination of certain physical and chemical characteristics of the activating serum factor from preparturient women and women with habitual abortions. AB - Follow-up investigation of the blood sera from preparturient women and women with habitual abortions showed the presence of a factor which has an activating effect on smooth muscle preparations because it causes the release of prostaglandins. Gel-chromatographic counter flow separation and microelectrophoresis of the blood sera have shown that the isolated serum factor is a water soluble glycopeptide with a molecular weight of about 2000. PMID- 4038490 TI - Phenylalanine ammonia-lyase immobilized in semipermeable microcapsules for enzyme replacement in phenylketonuria. AB - Phenylalanine ammonia-lyase immobilized within semipermeable microcapsules has an assayed enzyme activity which is 20% +/- 4% of the enzyme in free solution. The Km for the immobilized enzyme remained the same as that of the free enzyme. The pH optimum also remained unchanged at pH 8.5 +/- 1.0. At the lower pH range, enzyme activity is higher for the immobilized enzyme. Daily oral administration of microencapsulated phenylalanine ammonia-lyase to phenylketonuric rats decreased the systemic phenylalanine level by 35 +/- 8% in 2 days (P less than 0.05) and by 75 +/- 8% in 7 days (P less than 0.001). PMID- 4038491 TI - Effects of a commercial soy lecithin preparation on development of sensorimotor behavior and brain biochemistry in the rat. AB - Pregnant rat dams and offspring were exposed to a 5 or 2% soy lecithin preparation or a control diet. Enrichment was either lifelong beginning at gestation, limited to the time preceding, or the time following weaning, or absent (constituting a "pure" control group). The most marked early sensorimotor deficits (reflex righting and swimming development) were seen in the 5% soy lecithin preparation group, although all soy lecithin preparation-exposed offspring had elevated brain/body weight ratios and choline acetyltransferase levels. Later, animals exposed to lifelong 5 or 2% soy lecithin preparations were hypoactive, had poor postural reflexes, and showed attenuated morphine analgesia. The results indicate that dietary soy lecithin preparation enrichment during development leads to behavioral and neurochemical abnormalities in the exposed offspring. PMID- 4038492 TI - Diarrhoea and malabsorption in acquired immune deficiency syndrome: a study of four cases with special emphasis on opportunistic protozoan infestations. AB - Chronic diarrhoea is frequent in acquired immune deficiency syndrome (AIDS) but has been poorly investigated so far. We report four patients with AIDS in whom diarrhoea and malabsorption were outstanding features, and who underwent extensive digestive investigations. Diarrhoea was a presenting symptom in all subjects and was of secretory type in three of them. D-xylose and vitamin B12 were malabsorbed in all cases; steatorrhea was found in the two patients who could ingest significant amounts of fat. Faecal alpha 1-antitrypsin clearance was increased in all subjects. Search for digestive pathogens showed unusual protozoans in all patients: in case 1, optical and electron microscopy revealed the presence in the cytoplasm of villous enterocytes of Microsporidia protozoans still unreported in AIDS. Stool and jejunal fluid examination showed Isospora belli in case 2 and Cryptosporidium in cases 3 and 4. On histological and ultrastructural study the former was localised in the cytoplasm of a few enterocytes and the latter was scattered throughout the villus and crypt brush border. Otherwise small intestinal histology only showed minor non-specific changes and the enterocytes were ultrastructurally normal. In patient 3 the slow marker intestinal perfusion technique showed a profuse fluid secretion in the duodenum and proximal jejunum. All patients needed prolonged total parenteral nutrition. Cryptosporidium and Microsporidia could not be eradicated despite multiple drug trials. Isospora belli was transiently cured by pyrimethamine sulphadiazine. Only patient 2 is presently at home, and patients 1, 3, and 4 died after two, six, and nine months of total parenteral nutrition, respectively. PMID- 4038493 TI - Scanning electron microscopy of the liver cell cytoskeleton. AB - Rat livers were perfused with 0.5% Triton X-100 for 30 to 60 min and studied by scanning electron microscope. Three-dimensional filamentous networks were visualized in the cytoplasm of hepatocytes in situ. Branching and end-to-side contacts of intermediate filaments, and intermediate filaments which were connected with microtubules and microfilaments were noted. Numerous filaments were observed in the perinuclear region and at the cell border. Filaments were attached to polyribosomes and nuclei. No differences were observed in the cytoplasmic cytoskeleton after treatment of the sample at 4 degrees C. These results support the concept that intermediate filaments mechanically integrate the cytoplasmic space. PMID- 4038494 TI - PPS spurs changes in lab practices. AB - Change in the delivery of laboratory services is inevitable. However, the manipulation of several variables in conjunction with some realistic evaluation of current operations and cost-effective planning for the future can appropriately position the clinical laboratory in the marketplace. The demand for services, pricing, testing protocols, new equipment, staffing, productivity, and operational efficiency must all be weighed before the health care provider can determine the best course for a specific hospital clinical laboratory. PMID- 4038495 TI - Gc subtypes identified by isoelectric focusing in baboons (Papio hamadryas). AB - Phenotyping for Gc variants by conventional electrophoresis in 835 Papio hamadryas baboons demonstrated a monomorphic population. Gc subtyping by polyacrylamide IEF gels, pH 4-6, on 394 of these baboons revealed the existence of two common alleles which we named Gc1Papio and Gc2Papio. Pedigree data confirmed the inheritance of a single locus, two allele system and the observed gene frequencies were 0.593 for Gc1Papio and 0.407 for Gc2Papio. PMID- 4038496 TI - Lack of site of origin effects on distribution of IgA antibody-containing cells. AB - Previous experiments (Husband, 1982) indicated that IgA-specific antibody containing cells (ACC), appearing among thoracic duct lymphocytes (TDL) following challenge of intestinal segments of i.p. primed rats, display antigen-dependent distribution in the small intestine by 12 hr after their i.v. injection into autologous recipients. Data are presented here which demonstrate that ACC among TDL collected from rats bearing double Thiry-Vella loops challenged with two different antigens still appear almost exclusively in loops immunized with the antigen corresponding to their antibody specificity, even when injected into recipients in which immunized loops were prepared from different levels of the small intestine to that of the donors. These experiments indicate that, in animals given whole gut priming (by i.p. immunization) and segmental challenge (by lumenal challenge of isolated loops), the site of origin of IgA-ACC precursors does not influence antigen-induced distribution patterns. To determine whether segmental priming followed by whole gut challenge results in site of origin effects, rats were primed by subserosal immunization of a single Peyer's patch, either in the proximal or distal intestine, and then challenged intraduodenally. The ultimate IgA-ACC distribution was similar, regardless of the site of priming. These results indicate that, in a model employing priming with antigen in Freund's complete adjuvant, there is no site of origin effect on ultimate IgA plasma cell location within the small intestine, whether whole gut priming and segmental challenge or segmental priming and whole gut challenge, are used. PMID- 4038497 TI - Fibrinolytic activity of the retinae in streptozotocin-diabetic rats. AB - Fibrinolytic activity of the retinae in control and diabetic rats was assayed quantitatively in twenty male rats made diabetic by giving a single injection of streptozotocin. All these rats were killed at either 3 months or 12 months. Ten saline-injected rats and five rats treated with 3-0-methylglucose and streptozotocin served as controls. As the plasminogen activator activity in diabetic rats maintained for 12 months was significantly lower than that in controls, we postulate that there may be a poor defense mechanism against microthrombus formation in the retinal vasculature of diabetics, which may contribute to the development of diabetic retinopathy. PMID- 4038498 TI - Synthesis and secretion of interstitial retinol-binding protein by the human retina. AB - Interstitial retinol-binding protein (IRBP) is a soluble glycoprotein present between the retina and pigmented epithelium, which may function to shuttle vitamin A derivatives between these tissues. While previous studies have shown that the retina is solely responsible for IRBP synthesis, the specific retinal cell(s) in which this occurs has not been established. Since the carbohydrate moiety of IRBP contains fucose, the authors have analyzed the sites of incorporation of 3H-fucose in the human retina in vitro, using autoradiography. Following a 30-min pulse incubation, all retinal layers exhibited incorporation of label; however, the rod photoreceptor inner segments contained one- to two fold more radioactivity than was present in any other retinal compartment. In autoradiographs of retinas recovered following a 4 hr chase incubation, all retinal layers retained similar levels of radioactivity with the exception of the rod photoreceptors, cone photoreceptors and cells in the inner nuclear layer, which lost 75, 11, and 14 percent, respectively of the radioactivity present immediately following the 30-min pulse. Proteins present in the chase incubation medium were analyzed by polyacrylamide gel electrophoresis and fluorography. The principal labeled component in the chase medium was identified as IRBP by immunoprecipitation with antibovine-IRBP immunoglobulins. Thus, the major loss of 3H-fucose radioactivity from rod photoreceptors coupled with the appearance of 3H labeled IRBP in the incubation media suggests that the rod photoreceptors are primarily responsible for the synthesis and secretion of IRBP. PMID- 4038499 TI - Erysipelothrix rhusiopathiae endocarditis: report of a case and review of the literature. PMID- 4038500 TI - The effect of treatment in fractionated schedules with the combination of X irradiation and six cytotoxic drugs on the RIF-1 tumor and normal mouse skin. AB - RIF-1 tumors, implanted syngeneically in the gastrocnemius muscles of the right hind legs of C3H/Km mice, were treated either with X ray alone, drug alone, or drug and X ray combined. The drugs tested were bleomycin, BCNU, cis diamminedichloro platinum, adriamycin, cyclophosphamide, and actinomycin-D. All drugs were administered either in the maximum tolerated dose or a dose that causes minimal tumor growth delay. Both drugs and X rays were administered either as a single dose or in five daily fractions. In addition to the single modality controls, seven different schedules of combined modalities were tested. Tumors were measured periodically after treatment in order that the day at which each tumor reached 4 times its initial cross-sectional area, i.e., its size at the time of treatment, could be determined. The effect of treatment on tumors was based upon excess growth delay (GD), i.e., T400% (treated)-T400% (untreated control). Treatment effects for the same combined modality schedules were also determined for normal skin, using the early skin reaction as an endpoint. Dose effect factors (DEF) were computed for all combined modality schedules and were based upon calculated radiation dose equivalents. We also calculated supra additivity ratios, SRI and SRII, therapeutic gain factors and adjusted therapeutic gain factors. The only drugs to produce significant supra-additivity with X rays were cis-Pt and cyclo. Maximum supra-additivity for cis-Pt was afforded by divided doses of the drug (5 X 2.4 mg/kg/day) given immediately before X ray (5 X 1000 rad/day) on 5 consecutive days, although 3 other schedules also produced significant supra-additivity. Maximum supra-additivity for cyclo was seen for a single dose of 100 mg/kg followed 1 day later by a course of 5 daily X ray doses (5 X 1000 rad/day), and at least one other schedule produced almost as great an effect. PMID- 4038501 TI - Cytoskeletal calmodulin-dependent protein kinase. Characterization, solubilization, and purification from rat brain. AB - Brain calmodulin-dependent protein kinase was isolated as the major cytoskeletal component of the post-synaptosomal fraction, accounting for about 50% of the total protein. The alpha- and beta-subunits of the enzyme were present in a ratio of about 6:1. The cytoskeletal preparation was also distinguished by the regular presence of tubulin and actin in approximately equimolar amounts to the beta subunit. Electron microscopic morphology suggested that the enzyme formed a hierarchy of cytoskeletal complexes with an average diameter of 85 nm. These results indicate that cytoskeletal calmodulin-dependent protein kinase may have a structural as well as a catalytic role in neurons. The cytoskeletal enzyme could be solubilized in 8 M urea, displaying similar properties to its cytosolic counterpart. The postsynaptosomal cytoskeleton provides a simplified and well defined model for the study of the protein-protein interactions involving calmodulin-dependent protein kinase. PMID- 4038502 TI - Synthesis of unique low molecular weight proteins during late G2 and mitosis. AB - Changes in protein synthesis were examined during the cell cycle of Chinese hamster ovary cells by labeling synchronized cells at various times with [35S]methionine and separating the proteins on two-dimensional polyacrylamide gels. Several proteins, including tubulin, showed marked differences in their relative rates of synthesis during the cell cycle. A few proteins were found to be synthesized at a specific time during the cycle. In particular, a pair of proteins of approximately 21,000 daltons and isoelectric point of 5.5 were found to be synthesized only in late G2 and mitotic cells. Cells that were labeled during mitosis and then allowed to divide showed no trace of these proteins, indicating that their presence is transient and that they are likely involved in mitosis. PMID- 4038503 TI - A newly detected class of mammalian single strand-specific DNA-binding proteins. Effects on DNA polymerase alpha-catalyzed DNA synthesis. AB - Using a rapid purification scheme, we have isolated from calf thymus cells two single strand-specific DNA-binding proteins, with apparent molecular masses of 48 and 61 kDa. These proteins remained undetected in earlier studies on DNA-binding proteins from calf thymus because they are extremely sensitive to proteolytic breakdown occurring during purification. The proteins are immunologically and biochemically related. They also share a number of functional properties. Both proteins bind noncooperatively to single-stranded DNA and almost totally ignore double-stranded DNA. Both proteins stimulate DNA synthesis catalyzed by mammalian DNA polymerase alpha in the presence of an excess of "activated" DNA as primer template. The stimulation factor was between 2 and 100 depending on the protein/DNA ratio. We have analyzed this effect in more detail with specifically primed single-stranded phage fd DNA as template and concluded that the proteins block nonproductive polymerase-binding sites on single-stranded DNA sequences, thereby increasing the probability for an association of polymerase with 3'-OH primer ends. PMID- 4038504 TI - Cryptosporidiosis in immunocompetent children. AB - Cryptosporidial oocysts were identified by modified Ziehl-Neelsen stain in the stools of seven (3.2%) of 213 children with acute or chronic diarrhoea and one (0.9%) of 112 controls. All children with cryptosporidia were immunocompetent. Four of the index cases had a short illness (3-14 days) with watery diarrhoea, vomiting (2), and abdominal pain (2). Two index cases had chronic diarrhoea for over four months and failure to thrive. Both had a small intestinal enteropathy; one had cryptosporidial oocysts in stool specimens two months apart and the other had cryptosporidial schizonts attached to the jejunal mucosa. One index case had a colitis of indeterminate cause. Four of the index cases had recently travelled abroad. There had been an outbreak of gastroenteritis in the family of one of the index cases, and three affected sisters and an asymptomatic brother had oocysts in their stools. Cryptosporidial infestation seems to be associated with acute gastroenteritis and sometimes with chronic diarrhoea and small bowel damage in immunocompetent children. PMID- 4038505 TI - A twin study of genetic influences on behavioral deviance. PMID- 4038506 TI - Studies on the mechanism for renal elimination of N-acetylphenylalanine: its pathophysiologic significance in phenylketonuria. AB - To elucidate the mechanism and biologic significance of urinary occurrence of N acetylphenylalanine in phenylketonuria, the metabolic fate of N acetylphenylalanine was studied in rats. In vivo and in vitro analysis revealed that N-acetyl-14C(ul)-phenylalanine bound to plasma albumin with an association constant of 8.52 X 10(3) M-1 and that the number of binding sites was 0.98 per mole albumin. Intravenously administered N-acetylphenylalanine was rapidly extracted from the circulation predominantly by the kidney and excreted into urine. Plasma clearance of the injected ligand was markedly decreased by bilateral nephrectomy but not by bilateral ureter ligation. Probenecid, a potent inhibitor of the renal excretory system for organic anions, such as hippuric acid, sharply decreased the rate of disappearance from the circulation, renal accumulation, and urinary secretion of intravenously administered N acetylphenylalanine. These results indicate that intravenously administered N acetylphenylalanine undergoes renal peritubular transport via a probenecid sensitive excretory system for organic anions. This renal transtubular excretory mechanism may possibly operate in elimination of N-acetylphenylalanine, a hazardous amphipathic metabolite of phenylalanine, from plasma into urine in phenylketonuric patients. PMID- 4038507 TI - Changes in concentrations and rate of decline of adrenaline in the medial preoptic area and mediobasal hypothalamus of acutely ovariectomized steroid treated rats. AB - The presence of adrenaline within the central nervous system appears to be essential for the occurrence of an oestrogen-stimulated surge of LH in both pro oestrous and ovariectomized rats. Previous measurements of adrenergic activity based on the rate of decline of adrenaline (RDA) 2 h after injection of a synthesis inhibitor (SKF 64139) suggested that adrenergic activity increases in both the medial preoptic area (MPOA) and the mediobasal hypothalamus (MBH) at the start of the LH surge (15.00-17.00 h). The purpose of the present studies was to see whether oestrogen and progesterone affected this increase in adrenergic activity at the sites of the cell bodies (MPOA) and axon terminals (MBH) of the gonadotrophin-releasing hormone-synthesizing neurone. Rats ovariectomized at dioestrus showed a reduction in both plasma LH concentrations and RDA (P less than 0.01) in the MBH between 15.00 and 17.00 h on the day of expected pro oestrus. Oestrogen replacement at operation restored LH levels and the RDA to values found in intact rats. Injection of an antioestrogen (Cl-628), with or without oestrogen, also reduced plasma LH levels and the RDA (P less than 0.01) in the MBH. Removal or replacement of oestrogen apparently had little effect on the RDA in the MPOA. In ovariectomized oestrogen-primed rats an injection of progesterone on the morning of expected pro-oestrus advanced and enhanced not only the LH surge but also the RDA in the MBH (P less than 0.001). Moreover, concentrations of adrenaline in the MBH (but not the MPOA) decreased (P less than 0.001) consistently over a 2-h period following injection of progesterone.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4038508 TI - Plasma concentrations of somatomedin-C in hypophysectomized, dwarf and intact growing domestic fowl as determined by heterologous radioimmunoassay. AB - The application of a human somatomedin-C radioimmunoassay for the determination of somatomedin-C in chicken plasma has been examined. Parallel inhibition of binding of 125I-labelled somatomedin-C to antisera raised against somatomedin-C was observed with acid-treated human and chicken plasma. The concentration of immunoreactive (IR)-somatomedin-C in the plasma of the domestic fowl appears to be GH dependent. Plasma concentrations of IR-somatomedin-C were reduced after hypophysectomy and partially restored by replacement therapy with chicken GH. The age/development pattern of circulating concentrations of IR-somatomedin-C has been determined in normal and dwarf strains of domestic fowl. Increases in the plasma concentration of IR-somatomedin-C were observed between 1 and 6 weeks of age in control male domestic fowl of either heavy (broiler type) or light (White Leghorn) strains. Thereafter, the plasma concentrations of IR-somatomedin-C remained constant in the heavy strain birds but declined in White Leghorn chicks. Plasma concentrations of IR-somatomedin-C were reduced in sex-linked dwarf chickens, in both light and heavy strains of fowl, but were unaffected in autosomal dwarf chickens. PMID- 4038509 TI - Individual differences in anticipation of alcohol sensitivity. AB - Anticipations of the effect produced by a given amount of alcohol may be as important as actual responses to that amount of alcohol in determining patterns of alcohol use, yet previous research has focused only on physiological response and subjective reports of sensitivity upon administration of alcohol. In this study, the etiology of individual differences in reports of anticipated sensitivity was examined using a sample of 54 pairs of twins and adoptees for whom both members of each pair had consumed two drinks per hour for 2 hours at some time during the year before the study. Genetic influence was suggested for anticipated sensitivity to physical symptoms and coordination but not for other symptoms such as thinking problems, mood, or driving ability. The environmental influences responsible for individual differences in anticipated sensitivity are largely shared by family members, as indicated by the substantial resemblance for pairs of adoptees reared in the same family. Also explored was the correlation between anticipated sensitivity to alcohol and reported recent drinking behavior. In this sample (N = 204) it was found that an anticipation of less sensitivity related to a higher reported average number of drinks consumed per drinking session, independent of weight, sex, or age differences. PMID- 4038510 TI - High-dose cisplatin with sodium thiosulfate protection. AB - Nephrotoxicity frequently limits the dose of cisplatin to less than 120 mg/m2 per injection. Sodium thiosulfate is a neutralizing agent for cisplatin that protects against renal damage. To determine whether injection of thiosulfate would permit larger doses of cisplatin to be administered, a fixed 9.9-g/m2 dose of thiosulfate was given intravenously over three hours concurrently with escalating doses of cisplatin. Cisplatin was administered over the last two hours of the thiosulfate infusion. Using this technique, it was possible to escalate the cisplatin dose to 225 mg/m2 before dose-limiting toxicities were encountered. Comparison of cisplatin pharmacokinetics in patients treated with 202.5 mg/m2 plus thiosulfate to those in patients treated with 100 mg/m2 without thiosulfate indicated that there were no changes in the elimination rate constant, volume of distribution, or total body clearance of cisplatin. The total drug exposure for the plasma was approximately twofold at the higher cisplatin dose. This study demonstrates that concurrent administration of thiosulfate permits at least a twofold increase in dose and total exposure to cisplatin. PMID- 4038511 TI - High-dose intravenous metoclopramide versus combination high-dose metoclopramide and intravenous dexamethasone in preventing cisplatin-induced nausea and emesis: a single-blind crossover comparison of antiemetic efficacy. AB - We tested the safety and antiemetic effectiveness of intravenous (IV) dexamethasone (DXM) as an adjunct to high-dose IV metoclopramide (MCP) to prevent nausea and vomiting induced by high-dose cisplatin chemotherapy. Response was determined by using objective and subjective criteria. Thirty patients were randomly assigned to receive MCP alone at a dose of 2 mg/kg IV for three doses or the same dose of MCP plus 20 mg of DXM IV for three doses. Twenty evaluable patients received a second course of cisplatin and were crossed over to the opposite arm. Study results did not show a statistically significant advantage of combination MCP plus DXM over MCP alone using strict objective criteria for antiemetic response. However, patients subjectively preferred MCP plus DXM over MCP alone by nearly a 6:1 ratio, regardless of the randomization sequence. Although the addition of DXM does not appear to objectively improve emetic protection with high-dose MCP, we recommend MCP plus DXM to prevent nausea and vomiting induced by high-dose cisplatin chemotherapy when the use of steroids is not contraindicated, in view of patient preference for the combination. PMID- 4038512 TI - Absorption and tissue distribution of zinc, iron and copper by rats fed diets containing lactalbumin, soy and supplemental sulfur-containing amino acids. AB - Zinc, copper and iron utilization was examined in rats fed diets containing 30% lactalbumin (L); 30% soy assay protein (S) or 30% soy assay protein supplemented with 0.26% cysteine (SC), 0.45% methionine (SM), 0.26% cysteine and 0.45% methionine (SCM) or 0.71% cysteine (SXC). Diets L, SC and SCM contained equal amounts of cysteine; diets L, SM and SCM contained equal amounts of methionine; diets L, SCM, SXC contained equal amounts of sulfur-containing amino acids. Rats fed diet L had significantly higher levels of zinc in tibias, kidneys and plasma; higher levels of copper in kidneys; and higher levels of iron in tibias than rats fed diet S. Rats fed diet L also absorbed (apparent and true) significantly more zinc; excreted significantly more zinc of endogenous origin in the feces; and absorbed (apparent) significantly less copper than rats fed diet S. Rats fed the soy diets supplemented with sulfur-containing amino acids, especially diet SXC, tended to have elevated levels of zinc in their tibias and kidneys and greater apparent and true absorptions of zinc than rats fed diet S. Rats fed diet SXC still had significantly lower zinc levels in tissue than rats fed diet L. Apparent absorption of zinc was similar among rats fed diets L, SCM and SXC. PMID- 4038513 TI - Growth hormone secretory dynamics in Turner syndrome. AB - We investigated whether a decrease in serum growth hormone contributes to the short stature of adults with Turner syndrome by measuring the 24-hour profile of serum growth hormone in 30 patients aged 2 to 20 years. Growth hormone pulses were defined as a rise from nadir to peak that exceeded three times the intraassay coefficient of variation. Girls with Turner syndrome aged 2 to 8 years did not have statistically different growth hormone levels, peak amplitudes, and peak frequencies compared with those in age-matched controls. By contrast, girls with Turner syndrome aged 9 to 20 years had significantly decreased mean 24-hour growth hormone levels, peak amplitudes, and peak frequencies compared with those in age-matched normal girls. Patients with Turner syndrome of all ages had decreased serum somatomedin-C concentrations and delayed bone ages. We conclude that a relative deficiency of growth hormone in pubertal patients with Turner syndrome may contribute to their adult short stature. PMID- 4038514 TI - Photoperiod and delayed implantation in the northern fur seal (Callorhinus ursinus). AB - An equation for determination of the photoperiod at any given latitude for any given date is presented and used in an analysis of reproductive timing in the northern fur seal in which there is an obligatory delay of implantation. Fur seals breeding on San Miguel Island, California (33 degrees N) displayed a mean date of parturition that was 14 days earlier (P less than 0.001) than that of the parent stock on the Pribilof Islands, Alaska (57 degrees N). Previous studies have shown that changes occur in the corpus luteum, in follicles in the ovary containing the corpus luteum, in concentrations of plasma progesterone and oestradiol-17 beta, and in the uterine lining when there is a mean photoperiod of 12.5 h/day. This photoperiod occurs at both locations at 62 days after the mean dates of parturition, and may act as a cue for the initiation of implantation in these seals. PMID- 4038515 TI - Peripheral plasma prolactin concentrations during oestrous cycles in different types of primitive gilt. AB - Plasma prolactin concentrations were determined by radioimmunoassay during oestrous cycles and around the time of oestrus in different types of primitive gilts: Vietnamese, Zlotnicka and wild-boar X domestic pig hybrids. The animals were bled without stress from an indwelling arterial catheter. The following results were obtained: (1) in all gilts the main prolactin peak was observed at Day 15 or 16 of the oestrous cycle; (2) Vietnamese and hybrid gilts showed a second smaller prolactin surge after (Day 2) or before (Day 17) oestrus; (3) base levels of prolactin during the oestrous cycle were 14.8 +/- 0.93 ng/ml (Vietnamese gilts), 13.2 +/- 1.05 ng/ml (Zlotnicka gilts) and 15.6 +/- 2.01 ng/ml (hybrid gilts). The 15-16-day prolactin peaks reached maximum values of 36.4, 43.4 and 56.5 ng/ml respectively. PMID- 4038516 TI - Changes in pulsatile LH secretion after ovariectomy in Ile-de-France ewes in two seasons. AB - Two experiments were conducted in Ile-de-France ewes to study changes in pulsatile LH secretion in ewes ovariectomized during anoestrus or during the midluteal phase of the oestrous cycle. In Exp. 1, blood samples were taken every 20 min for 12 h the day before ovariectomy (Day 0). After ovariectomy, samples were taken every 10 min for 6 h (10 ewes per group), on Days 1, 3, 7 and 15. In Exp. 2 samples were taken every 10 min for 6 h (10 ewes per group) on Days 7, 15, 30, 60, 90, 120, 150 and 180 after ovariectomy. Further samples were taken (5 ewes per group) at 9 and 12 months after ovariectomy. There were significant interactions between season and day of sampling for the interval between LH pulses in both experiments. LH pulse frequency increased within 1 day of ovariectomy and the increase was more rapid during the breeding season. There were clear seasonal differences in pulse frequency in Exp. 2. Compared with ewes ovariectomized in anoestrus, pulse frequency was significantly higher for ewes ovariectomized in the breeding season, from Day 7 until Day 120. Once pulse frequency had increased in ewes about the time of the normal breeding season, pulse frequency remained high and subsequent seasonal changes were greatly reduced. Pulse amplitude increased immediately after ovariectomy to reach a maximum on Day 7 and there were no differences between season of ovariectomy in the initial changes in amplitude. In Exp. 2, changes in amplitude followed changes in pulse interval and there was a significant interaction between season and day of sampling. There were no significant effects of season on nadir LH concentrations which increased throughout the duration of the experiments. These results show that, in ovariectomized ewes, LH pulse frequency observed on a given day depends on time after ovariectomy, season at the time of sampling and on previous exposure of ewes to stimulatory effects of season. The direct effects of season on LH pulse frequency and seasonal changes in sensitivity to steroid feedback may contribute to control of the breeding season and their relative contributions to the beginning and end of the breeding season may differ. PMID- 4038517 TI - Rate and course of atresia during follicular development in the adult cyclic rat. AB - Ovarian follicles (greater than or equal to 100 X 10(5) microns 3 or a mean diameter of greater than or equal to 275 microns) in adult rats were classified as non-atretic and atretic during the oestrous cycle and recorded in 5 volume classes. The atretic follicles were also categorized in several stages according to the progress of atresia. The degeneration of the entire granulosa wall until the induced changes in the oocyte took at least 24 h. Another 24 h elapsed before the oocyte became denuded. Therefore the % of atretic follicles, i.e. follicles in all stages of atresia, could not be used as indicator for the rate of atresia. The atretic portion in the follicle population greater than or equal to 100 X 10(5) microns 3 increased from early dioestrus 1 to early dioestrus 3, reached a plateau during dioestrus 3 and pro-oestrus, and declined at late oestrus to the level of early dioestrus 1. The sudden decrease in number of atretic follicles after late pro-oestrus was caused by the discard of many atretic follicles in the advanced stages due to various deformities as revealed by histological observation. By using the % of atretic follicles in the earliest stage as indicator of atretic rate, two waves of atresia were found affecting the population of antral follicles during their growth, the first at dioestrus 1 amounting to 15-20% and then at dioestrus 3, affecting 35% of the population. The present study also shows the extension of atresia in the various volume classes of follicles during the oestrous cycle. A pool of approximately 7 follicles in the smallest volume class was maintained after ovulation, grew further in the next cycle with a new cohort of 20 follicles, and seemed to provide the required number of follicles destined to ovulate. This suggests that the follicles that ovulate were already present at an antral stage in the preceding cycle and needed two cycles for their growth to ovulation. PMID- 4038518 TI - Structure of the oviducal epithelium of the brush-tailed possum (Trichosurus vulpecula). AB - Observations were made using scanning and transmission electron microscopy and were correlated with measurements of the mean surface area and the percentage area occupied by secretory cells to provide precise interpretation of the morphological data. In cyclic and anoestrous possums the oviducts were lined with elaborate folds of mucosa except in the portion of the isthmus adjacent to the uterus where the pattern was much simplified. The folds decreased in height and number after ovariectomy. Secretion was maximal between oestrus and Day 2 of the cycle when most ovulations take place. Extrusion of vesicles was observed in the ampulla and isthmus at this stage although the process was localized to some extent because groups of cells with actively extruding vesicles were interspersed with others which contained vesicles but otherwise appeared inactive. This is interpreted as a device whereby a constant supply of secretion can be maintained over several days. Secretory activity declined between Days 3 and 8 and the epithelium in mid-cycle (Days 8-18) appeared relatively quiescent. By Day 24 there was morphological and morphometric evidence of a return to oestrous conditions, although vesicles had not yet reappeared in secretory cells. Ciliogenesis was prevalent at this time and is probably related to the ovum transport that will occur several days later. PMID- 4038519 TI - Smith-McGuckin spot. AB - Direct inspection of the tympanic membrane, especially with the help of the microscope, continues to be an important part of the examination of the patient suffering from ear disease. Accurate assessment of the varied appearances can be helpful in anticipating the prognosis in SMOM and may give information about the pathology of CSOM and cholesteatoma. The Smith-McGuckin spot was first described 20 years ago (Smith 1964, R Thomas 1965, personal communication) and its significance is reviewed. Further evidence of the relationship between skeletal disorders such as Turner's syndrome and persistent SMOM is described. It is suggested that bone resorption in the deep meatus, outer attic wall and ossicles may result from chronic hyperaemia rather than sepsis or avascular necrosis. The part played by cholesteatoma in bone erosion is questioned. PMID- 4038520 TI - Characterization of infectious hematopoietic necrosis virus mRNA species reveals a nonvirion rhabdovirus protein. AB - The genome RNA and six mRNA species of infectious hematopoietic necrosis virus were analyzed by denaturing gel electrophoresis. The following molecular weights were determined: genome RNA, 3.7 X 10(6); mRNA 1, 2.26 X 10(6); mRNA 2, 5.63 X 10(5); mRNA 3, 4.84 X 10(5); mRNA 4 (containing two different mRNA species), 3.00 X 10(5); and mRNA 5, 1.95 X 10(5). Densitometer analyses of gels were used to calculate the molar ratios of the intracellular mRNA species: mRNA 1, 0.02; mRNA 2, 0.49; mRNA 3, 1.0; mRNA 4, 2.52; and mRNA 5, 0.41. Hybrid selection studies determined the mRNA coding assignments as follows: mRNA 1 encodes the viral polymerase, L; mRNA 2 encodes the glycoprotein, G; mRNA 3 encodes the nucleocapsid protein, N; mRNA 4 is composed of two comigrating mRNA species which encode the matrix proteins, M1 and M2; and mRNA 5 encodes a previously unrecognized viral protein which is induced in infected cells but is not present in mature virions. This nonvirion protein has been designated the NV protein. PMID- 4038521 TI - Virions and intracellular nucleocapsids produced during mixed heterotypic influenza infection of MDCK cells. AB - Phenotypically mixed virus yields, obtained by coinfection of MDCK cells with influenza A/WSN/33 and B/Lee/40 viruses, contained both A/WSN/33 and B/Lee/40 NP proteins, as revealed by polyacrylamide gel electrophoresis of the purified 14C amino acids-labeled virus. Virions were lysed with 0.6 M KCl-Triton X-100 buffer, and nucleocapsids were immunoprecipitated with antibodies against NP protein of influenza A virus. Polyacrylamide gel electrophoresis of the immunoprecipitate revealed NP protein of A/WSN/33 but not of B/Lee/40 virus. However, in similar experiments with the lysates of doubly infected cells, the band of B/Lee/40 NP protein was revealed in the polyacrylamide gel electrophoresis patterns of the immunoprecipitates. In an attempt to analyze the RNA content of the immune complexes, we absorbed the lysates of doubly infected [3H]uridine-labeled cells with protein A-containing Staphylococcus aureus covered with antibodies against the NP protein of influenza A virus. RNA extracted from the immune complexes contained genomic RNA segments of both A/WSN/33 and B/Lee/40 viruses. In control samples containing an artificial mixture of cell lysates separately infected with each virus, the analysis revealed homologous components (i.e., A/WSN/33 NP protein or RNA segments) in the immune complexes. The results suggest the presence of phenotypically mixed nucleocapsids in the cells doubly infected with influenza A and B viruses; in the course of the virion formation, the nucleocapsids lacking the heterologous NP protein are selected. PMID- 4038522 TI - Intraoperative profilometry. AB - Intraoperative profilometry measurements were done on 28 patients during various types of urethropexy to determine whether useful information could be provided to the operating surgeon. Successful Burch, Marshall-Marchetti and Stamey-Pereyra procedures resulted in a 50 per cent increase in urethral length. Closure pressure increases were noted only with the Stamey-Pereyra procedure (plus 49 per cent). Intraoperative profilometry measurements were considered to be informative and useful, particularly during the Stamey-Pereyra urethropexy in which case suture ties could be regulated to provide desired urethral elongation and closure pressure changes. PMID- 4038523 TI - Evacuation of the bladder via abdominal urethrostomy. PMID- 4038524 TI - Ectopic ureterocele in an adult with prolapse through the urethra. AB - Most ureteroceles in adults are incidental findings at excretory urography. Symptomatic ureteroceles are unusual and prolapse of the ureterocele is particularly uncommon. We describe a woman with prolapse of a ureterocele through the urethra, which resulted in strangulation and partial necrosis of the ureterocele wall. PMID- 4038525 TI - Acute gastric anisakiasis. Analysis of 178 cases. AB - From 1969 to 1984, we treated 178 patients with acute gastric anisakiasis caused by gastric mucosal penetration of the Anisakis larvae. Because the larvae of Anisakis can always be observed by endoscopy and removed with biopsy forceps, early performance of endoscopy is highly recommended for patients in whom acute gastric anisakiasis is suspected and for those who have eaten raw fish within 12 hours before onset of the gastric symptoms. Endoscopic removal is essential to relieve the intolerable pain; after relief, the administration of antacids will repair the damaged gastric mucosa. Ulcer formation is rare. PMID- 4038526 TI - Anisakiasis from the American perspective. PMID- 4038527 TI - Effect of branched-chain amino acids and insulin on postinjury protein catabolism in growing animals. PMID- 4038529 TI - [Causes of individual differences in aging--a study of separately raised twins]. PMID- 4038528 TI - The importance of prostaglandin E1 in resuscitation of the neonate with critical aortic stenosis. PMID- 4038530 TI - A diurnal variation of hepatic acid cholesteryl ester hydrolase activity in the rat. AB - The diurnal variation in lysosomal acid cholesteryl ester hydrolase (Acid CEH), (EC 3.1.1.13) has been examined in fed, fasted and adrenalectomized rats. The Acid CEH activity of normal rat liver exhibits a diurnal rhythm with maxima at 06.00 hours and minima at 18.00 hours, but such a rhythm was not observed in spleen and brain. This rhythm was abolished after fasting for two days, and the resulting Acid CEH activity remained constant at the minimum level. However, adrenalectomy did not abolish the diurnal rhythm. These results indicate that the Acid CEH activity varies according to a diurnal rhythm with maxima and minima separated by approximately 12 hr. Further, it is evident that the appearance of this rhythm is dependent upon dietary, but not adrenal hormone influence. PMID- 4038531 TI - Withdrawal and withholding of life-support in terminally ill patients. Part II. PMID- 4038532 TI - The Austrian situation concerning voluntary and non-voluntary hospitalization. PMID- 4038533 TI - Domestic violence. PMID- 4038534 TI - Clinical criminology: an emerging profession. PMID- 4038535 TI - The United States Supreme Court and mental health law. A retrospective. PMID- 4038536 TI - In vino veritas?: Police interrogation of intoxicated persons and the requirement of voluntariness. PMID- 4038537 TI - Outpatient treatment of alcohol addicts. The Burgenland model. PMID- 4038538 TI - Multiple self-inflicted gunshot wounds. A case report. PMID- 4038539 TI - Ben-Ari v. Shapira: contempt proceedings against mentally ill persons in the Supreme Court of Israel Civil Appeal. PMID- 4038540 TI - Constitutionality of a city ordinance regulating the performance of abortion (city of Akron v. Akron Center of Reproductive Health). US Supreme Court, Decision Nos. 81746, 811172, June 15, 1983 (Supreme Court Reporter = S.Ct. 103 (1983, 2481-2517). PMID- 4038541 TI - Remarks on telling the truth or lying. PMID- 4038542 TI - Ethanol-induced alterations in rat synaptosomal plasma membrane phospholipids. Relationship to changes in the phospholipid methyltransferases. AB - The effects of ethanol ingestion on the lipids of the synaptic plasma membrane (SPM) have been measured and correlated with the time frame for the development of physical dependence. Alterations were observed in three of the phospholipid fractions: phosphatidylcholine (PC) increased, and the phosphatidylethanolamine (PE) and phosphatidylserine (PS) plus phosphatidylinositol (PI) fractions decreased. These alterations occurred after the animals showed signs of dependence. Because PC can be synthesized from PE by the methyltransferase pathway, synaptosomal methyl group incorporation was measured. Rats were fed ethanol for 6 days before an increase was observed in methyl incorporation, a shorter length of time than was necessary to demonstrate physical dependence or phospholipid alterations (10 to 14 days). After ethanol withdrawal, 7 days of control diet feeding were required for methyl group incorporation to return to control values. In vitro ethanol (10-250 mM) additions to the methyltransferase incubations resulted in a slight increase in methyl incorporation. These data suggest that synaptic membrane lipid alterations may be related to ethanol dependence and that changes in the PC/PE ratio may be the result of an increase in the incorporation of methyl groups into synaptosomal phospholipids. PMID- 4038543 TI - Studies on chromosome aberrations in the eggs of mice fertilized in vitro after irradiation. I. Chromosome aberrations induced in sperm after X-irradiation. AB - The induction of chromosome aberrations in eggs of mice fertilized with X irradiated sperm was performed by using an in vitro fertilization technique. Capacitated mature sperm was irradiated with various doses of X-rays and cytological analysis of the first cleavage metaphase of in vitro fertilized eggs was made. The frequencies of chromosome aberrations increased exponentially with dose and the dose-response relationship for overall breaks fitted well to a quadratic equation. The chromosome aberrations were mainly chromosome-type (82.1%), and the majority of aberrations were fragments. PMID- 4038544 TI - Successful reversal of echovirus encephalitis in X-linked hypogammaglobulinemia by intraventricular administration of immunoglobulin. PMID- 4038545 TI - Skeleton key to memory? PMID- 4038546 TI - Growth hormone secretion during long-term thiopental anesthesia in the adult male rat. AB - To study the secretory pattern of growth hormone (GH) in the adult male rat in a continuous sleep state, the GH concentration was measured in blood sampled at 10 min intervals through an intracardiac cannula for 9-10 h long-term anesthesia with thiopental sodium. The cortical EEG was monitored to maintain stable EEG sleep throughout the sampling period. In 41 animals subjected to anesthesia, 32 showed an apparent fluctuation in GH levels. The analysis of the time series of the GH concentration in blood by the power spectrum and least-squares method revealed that 27 animals had periodicities within the mean +/- 2SD range obtained for the unanesthetized, but similarly sampled, animals from 2.40 to 3.85 h. The mean (+/- SE) of the periodicities for 27 animals was 3.01 +/- 0.06 h, similar to that obtained for the unanesthetized animals, approximately 3.0 h. The results indicate that, although the GH-controlling mechanism in the rat is facilitated under sleep, it has a 3.0-hour period ultradian rhythm mechanism that is independent from that for sleep. PMID- 4038547 TI - Maternal and perinatal morbidity resulting from placenta previa. AB - One hundred forty-seven cases of partial or complete placenta previa from 1975 to 1982 were reviewed. A history of prior cesarean section was associated with a significant increase in maternal morbidity, including massive hemorrhage, placenta accreta, and hysterectomy. Despite tocolysis and transfusions to delay delivery, nearly two-thirds of the patients were delivered before 36 weeks' gestation. Onset of bleeding before 20 weeks' gestation was associated with a very poor fetal prognosis. The perinatal mortality rate was 81 of 1000. The overall incidence of respiratory distress syndrome was 22%; this was a major cause of neonatal mortality and morbidity. There was a statistically significant correlation between antepartum maternal hemorrhage and the need for neonatal transfusion, and between the neonatal anemia and the amount of intrapartum maternal blood loss. PMID- 4038548 TI - Systemic acyclovir in pregnancy: a case report. AB - Disseminated herpes simplex infection in pregnancy presents serious risk to mother and fetus. Although an uncommon problem, the high maternal and fetal mortality and morbidity accompanying disseminated herpes infection warrants aggressive new treatment. Specific antiviral chemotherapy is now possible for selected cases. The present report describes the use of acyclovir during the third trimester for disseminated herpes simplex infection. The treatment protocol used and pregnancy outcome are described for this case. Acyclovir therapy and potential toxicities are described. PMID- 4038549 TI - Synergic effect of cisplatin, Adriamycin, and cyclophosphamide combination chemotherapy and radiotherapy in non-small cell lung cancer. AB - 61 patients with inoperable non-small cell lung cancer were treated by combination chemotherapy with cisplatin, Adriamycin and cyclophosphamide. 23 patients received radiotherapy in addition to the chemotherapy. 49 out of 55 adequately treated patients were evaluable for tumor response. Of 29 patients who received chemotherapy alone, 6 (21%) achieved partial responses. Of 20 patients who received combined chemotherapy and radiotherapy, 16 (80%) achieved complete or partial responses. The median survival time was 18 months for 22 patients treated with combined therapies. PMID- 4038550 TI - Droperidol as an antiemetic in cis-platinum-induced nausea and vomiting. AB - 23 patients received cis-platinum, doxorubicin and cyclophosphamide for gynecologic malignancy between December 1, 1980 and December 1, 1982. Each patient was randomized with each course of chemotherapy to receive intravenous droperidol or the combination of promethazine and chlorpromazine rectal suppositories as an antiemetic regimen. Both the rate and duration of emesis were significantly lower when droperidol was used as the antiemetic regimen. There were no major side effects with either regimen. Droperidol seems to be superior to the combination of promethazine and chlorpromazine rectal suppositories in alleviating cis-platinum-induced nausea and vomiting. PMID- 4038551 TI - [Estrogen and progesterone receptors in endometrial carcinoma following endometrial radiation therapy]. PMID- 4038552 TI - Inhibitory effect of maternal alcohol ingestion on rat pup hepatic 25 hydroxyvitamin D production. AB - The mechanisms underlying the teratogenic effects of alcohol are unknown, and may reflect metabolic differences between adult and fetal tissues. The liver is the major site of alcohol metabolism and the sole site of 25 hydroxyvitamin D synthesis. We have compared 25-hydroxyvitamin D production in adult nonpregnant, maternal, and pup livers obtained from vitamin D-deficient animals and examined the effects of alcohol ingestion on hepatic vitamin D metabolism. 25 Hydroxyvitamin D production was comparable in adult nonpregnant and maternal livers, but was decreased in pup livers compared to their maternal controls (1.4 +/- 0.2 versus 0.6 +/- 0.1 pmol/g protein/h, p less than 0.001). Alcohol ingestion for 18 days had no effect on hepatic synthesis of 25 hydroxyvitamin D in the adult livers, but inhibited production by the pup livers (0.6 +/- 0.1 versus 0.3 +/- 0.1 pmol/g protein/h, p less than 0.02). To assess the physiologic significance of these observations, the effect of alcohol on 25-hydroxyvitamin D levels in vitamin D-replete mothers and fetuses was determined. Alcohol had no effect on circulating 25 hydroxyvitamin D levels in the mothers but lowered fetal 25 hydroxyvitamin D content (2.3 +/- 0.3 versus 1.2 +/- 0.3 ng/g fetus, p less than 0.02) without altering fetal weight. The data indicate that differences exist in pup and adult hepatic metabolism of vitamin D and that alcohol has inhibitory effects on pup liver function not expressed in adult tissues. PMID- 4038553 TI - Oral dexamethasone for treatment of persistent middle ear effusion. AB - A double-blind controlled study of oral dexamethasone (in a 2-week tapering dose from .15 mg/kg/d) v placebo in 49 pediatric patients (mean age 3.7 years) with persistent asymptomatic middle ear effusion of three or more weeks duration was conducted. Middle ear effusion resolution was determined by a myringotomy validated algorithm that combined pneumatic otoscopy and tympanometry. Four weeks after completing treatment, 1/26 (4%) patients receiving dexamethasone and 2/23 (9%) patients receiving placebo had completely cleared their middle ear effusion (95% confidence interval -0.05 +/- 0.14). Five of 26 (19%) patients receiving dexamethasone and 6/23 (26%) patients receiving placebo had improved their hearing in all affected ears by 10 dB or more (95% confidence interval -0.07 +/- 0.23). Oral dexamethasone as used in this study was not effective in treating persistent middle ear effusion in children. PMID- 4038554 TI - Phototherapy for hyperbilirubinemia of hemolytic disease of the newborn. PMID- 4038555 TI - Nutrition and prostate cancer: a case-control study. AB - This one-to-one, age- and race-matched case-control study involved 181 histologically confirmed black prostate cancer patients and 181 controls seen at three major hospitals in Washington, DC, during the period 1979-1982. Personal interviews were conducted to obtain the number of times food items of specified serving size were consumed per week by cases and controls during the age periods 30-49 and 50 years and older. Then the average daily consumption of each of 18 nutrients per 1,000 calories was calculated. There was risk enhancement associated with increased intake of proteins, total fat, saturated fat, oleic acid, and vitamin A during the age period 30-49 years. The association was highly significant for vitamin A and approached statistical significance for the other four nutrients. A hypothesis based on disturbance of the zinc-retinol binding protein-vitamin A axis was put forward to explain the relative risk enhancement effect of vitamin A on prostate cancer. PMID- 4038556 TI - Retrograde amnesia produced by electron beam exposure: causal parameters and duration of memory loss. AB - The production of retrograde amnesia (RA) upon electron beam exposure has been investigated. RA production was evaluated using a single-trial avoidance task across a 10(4) dose range for 10-, 1-, and 0.1-microsecond pulsed exposures. The dose-response curve obtained at each pulse duration showed significant RA production. The most effective dose range was 0.1-10 rad at a dose rate of 10(6) rad/sec. By employing a 10 rad (10(6) rad/sec) pulse, a memory loss of the events occurring in the previous 4 sec was demonstrated. The conclusion was that the RA effect might be due to sensory system activation which provided a novel stimulus that masked previous stimuli. PMID- 4038557 TI - [Artificial insemination. Another resource in the treatment of infertility]. PMID- 4038558 TI - [2 + 2] photocycloadditions in the synthesis of chiral molecules. AB - A strategy for the synthesis of chiral molecules that receives growing popularity among organic chemists employs the photochemically mediated [2 + 2] cycloaddition reaction. These reactions can be performed on a multigram scale and often proceed with high yield and with stereocontrol. These features, in combination with the useful properties of the four-membered ring photoproducts in subsequent chemical transformations, make them attractive options in the early stage of a synthesis design. Various combinations of unsaturated functional groups can participate in this reaction process. Accordingly, these chemical reactions can be economical solutions to problems relating to the synthesis of a variety of target molecules. PMID- 4038559 TI - [Hemangiosarcoma of the breast]. PMID- 4038560 TI - Glycerol dynamics in weight-losing cancer patients. AB - This study was designed to show whether weight-losing cancer patients have an elevated glycerol turnover. Four groups of patients were examined: weight-losing cancer patients, weight-losing patients without cancer, cancer patients without weight loss, and weight-stable and well-nourished hospitalized control patients. Glycerol was infused intravenously at three different rates (200, 400, and 800 mumol/hr/kg body weight) after an overnight fast. This allowed measurement of clearance and plasma glycerol turnover. Weight-losing cancer patients (group 1) had an almost threefold higher glycerol turnover per kilogram of body weight compared with malnourished and well-nourished noncancer patients. However, both malnourished cancer and noncancer patients had an elevated glycerol turnover compared with well-nourished patients when glycerol turnover was related to whole body lipids. The results how that progressive clinical cancer is associated with an elevated plasma glycerol turnover, probably indicating an increased whole body lipolysis. This may explain the loss of body fat during the development of cancer cachexia. PMID- 4038561 TI - [Behavioral disorders in animals of stock farms]. AB - Intensively kept farm animals often show behavioural disturbances; some of these disturbances will cause pain (injurious behaviour), others will reflect pain (limping, colic). Also, the very common stereotypies are associated with pain. These stereotypies are characterized by their constant form and senseless repetitions. Stereotypies of tethered sows would appear to be specifically related with endorphins; they may act as agents promoting the release of endorphins and thereby calming the animal. This tranquilizing and protective function of stereotypies may play a role in veal calves showing abomasal injury. It was found that those calves that displayed most stereotypies had the least abomasal damage. Finally, a model is described, which makes it clear why emotions are essential in the behaviour of man and animals. PMID- 4038562 TI - [Evaluation of remission of progressive tumors treated with a simultaneous combination of radiation and platinum therapy]. AB - Since January 1982, we have treated in a phase-II study 28 patients with a low dose cis-platinum therapy combined with radiotherapy. We wanted to study the effect of reduced doses of cis-diamino-dichloroplatinum (II) in three different dose patterns: 1. "higher" dosage (150 mg/m2 within six weeks), single dose: 25 mg/m2 one time per treatment week), 2. "medium" dosage (80 mg/m2 within six weeks), single dose: 20 mg/m2 two times weekly during the first, fourth, seventh, and tenth treatment week, 3. "lower" dosage (75 mg/m2 within six weeks), single dose: 12.5 mg/m2 three times weekly during the first, fourth, seventh, and tenth treatment week. In one patient group the simultaneous radiotherapy was performed with a tumoricide dose of 2 Gy single dose with 4 fractions per week in two series (first series about 40 to 48 Gy tumor dose, pause of three to four weeks, second series about 16 Gy focal dose). The other group received palliative radiation doses (10 to 35 Gy tumor dose in one series), and the total platinum doses were lower corresponding to the shorter irradiation time. All patients were in advanced or recurrent stages of the disease. They suffered from different carcinomas and sarcomas with measurable parameters of response. RESULTS: 1. Manifestations beyond the irradiation field showed no remission. Within the irradiation field, all cases responded (CR/PR) for at least two months. 2. There was no reliable dependence from the platinum dose. A tendency in favor of higher single doses could be supposed. The response of even extreme palliative cases with low radiation and platinum doses was surprising. Limitating toxicities were not observed. PMID- 4038563 TI - [Rupture of the pregnant uterus after salpingectomy]. PMID- 4038564 TI - Female bladder neck reconstruction. Anatomic and physiologic approach. AB - Postoperative scarring of the bladder neck and urethra after failed anti incontinence surgery in the female can seriously disrupt the normal mechanisms of bladder storage and emptying. We have analyzed and treated this problem in 10 selected female patients. A "wrap-flap" technique with omental support has been applied to reconstitute the normal anatomy and physiology of the bladder neck. Excellent results were obtained in all patients, with up to fifty-four months of follow-up. We recommend this procedure prior to the implantation of prosthetic material, with its inherent difficulties. PMID- 4038565 TI - Radical cystectomy and adjuvant chemotherapy. AB - Seventy-one radical cystectomies were performed at the University of Tennessee from June, 1976, through December, 1983. The operative mortality rate was 1.5 per cent. The early and late complication rate was 21 and 15 per cent, respectively. Single agent cisplatin was used as adjuvant chemotherapy in patients at high risk for development of metastatic disease and did not alter the poor survival of this group of patients. PMID- 4038566 TI - [Today's diagnostic possibilities in cardiomyopathies]. PMID- 4038567 TI - Changes of molecular forms of growth hormone in bromocriptine treated acromegaly in relation to changes of somatomedin-C and clinical response. AB - Eleven patients with active acromegaly were treated with 10-20 mg bromocriptine daily for a period of 6-9 months. The clinical response was evaluated by a 'clinical and metabolic improvement score'. The biochemical response was evaluated by measurement of both the mean plasma growth hormone (GH) level during the day and the somatomedin-C (Sm-C) concentration. Before and at the end of the treatment period plasma samples were fractionated by Sephadex G-100 chromatography in order to study the effects of chronic bromocriptine treatment on the concentrations of total GH and its different molecular forms. The main observations may be summarized as follows: Three immunoreactive components were observed on Sephadex chromatography corresponding to molecular weight above 100 000 (big-big GH), 40 000-60 000 (big GH) and 20 000-22 000 (little GH). Bromocriptine treatment induced preferentially a reduction of little GH. There was a very good correlation between the decrease of little GH and total GH, and both were significantly correlated with the clinical response. The correlation between the decrease of Sm-C values and that of little and total GH as well as between the decrease of Sm-C and the clinical response was poor. It is concluded that a) measurement of little GH is not superior to the determination of total GH in the assessment of disease activity of bromocriptine treated acromegalic patients; b) both methods are superior to the measurement of plasma Sm-C levels; c) clinical response out of proportion ot the fall of total GH which can be explained by a preferential reduction of little GH, has not been observed in our investigations. PMID- 4038568 TI - Forskolin stimulation of adenylate cyclase in human thyroid membranes. AB - Forskolin stimulates adenylate cyclase in human thyroid membranes approximately 7 fold with half-maximal stimulation occurring at 5-10 microM. Guanine nucleotides are not required for stimulation of the enzyme by forskolin. Forskolin stimulation is additive or greater than additive with that of TSH or Gpp(NH)p- (above 1 microM). Different from TSH- or Gpp(NH)p-stimulation of adenylate cyclase, uncoupling of the guanine nucleotide-binding regulatory component by increasing concentrations of MnCl2 did not result in uncoupling of forskolin stimulation. The finding indicates that forskolin may mainly act on the catalytic component of adenylate cyclase. From the present study, it is suggested that the diterpene forskolin stimulates adenylate cyclase in human thyroid membranes by a novel mechanism that differs from TSH- or Gpp(NH)p-stimulation, and that the diterpene may be a useful tool to investigate the metabolism of thyroid and its regulation in normal and pathological situations. PMID- 4038569 TI - Oxytocin can affect follicular development in the adult mouse. AB - Injection of oxytocin into normal adult cycling mice caused alterations in ovarian histology. Oxytocin was administered early on the day of pro-oestrus and it induced the appearance of large numbers of corpora lutea by late pro-oestrus, suggesting oxytocin stimulated ovulation. When mice were examined very early on the day of normal oestrus the ovarian population of follicles was different in the experimental group from that in the control mice, there being increased numbers of preantral and antral follicles in treated animals. As oxytocin can cause an alteration in the timing of follicular maturation and ovulation processes study of communications between the adenohypophysis and areas containing oxytocin might be important for understanding physiological details of ovulation. The relative times at which, for instance, antral follicle and corpora lutea populations increased suggested that oxytocin might have more than one activity which affects ovarian behaviour. PMID- 4038570 TI - Studies of the human testis. XIX. Preparation of an antibody to human testosterone-oestradiol-binding globulin and its application to the study of testicular androgen-binding protein. AB - Human testosterone-oestradiol-binding globulin (hTeBG) was purified from pregnancy serum by ammonium sulphate precipitation, preparative flatbed electrofocusing, Concanavalin A-Sepharose affinity chromatography, Sephadex G-150 gel filtration, DEAE-Sephadex chromatography and preparative polyacrylamide gel electrophoresis. The yield was 0.3 mg of hTeBG with a specific acitivity of 1.1 nmoles DHT bound per mg. An antiserum to TeBG was raised in rabbits. Anti-hTeBG IgG was separated from rabbit TeBG by DEAE-Affi-Gel-Blue chromatography. Anti hTeBG was titrated using protein A-Sepharose which quantitatively binds IgG and therefore bound [3H]DHT-hTeBG-anti-TeBG complexes. The androgen binding components from human testis were separated on Concanavalin A-Sepharose columns into excluded and retained fractions. The antibody bound both testis fractions with titration curves which paralleled that of TeBG, indicating that these androphilic proteins share common immunodeterminants with hTe-BG. The possibility that these testicular proteins are identical in amino acid sequence to TeBG and differ only in carbohydrate content will require further verification. Finally, these results indicate that antibodies to TeBG can be used to study human testicular androgen-binding protein. PMID- 4038571 TI - Value and limitations of radionuclide angiography in determining the cause of reduced left ventricular ejection fraction: comparison of idiopathic dilated cardiomyopathy and coronary artery disease. AB - The radionuclide angiograms of 59 patients with a left ventricular (LV) ejection fraction (EF) less than 0.40, 23 with idiopathic dilated cardiomyopathy (IDC) and 36 with coronary artery disease (CAD) were analyzed to assess the usefulness of radionuclide angiography in distinguishing these conditions. Mean right ventricular EF was lower in the IDC group than in the CAD group, 0.31 vs 0.45 (p less than 0.01). LV wall motion was scored from 3 (normal) to -1 (dyskinesia). The incidence of akinesia was similar in IDC and CAD groups, 70% and 83%, respectively. Dyskinesia was more common in the CAD group (42% vs 17%), but the difference was not statistically significant. Segmental wall motion analysis showed similar patterns of wall motion in both groups, with contraction best preserved in the anterobasal, posterobasal and superolateral segments. Patients in the CAD group had worse apical motion (p less than 0.01) and better wall motion in the anterobasal (p less than 0.05) and superolateral walls (p less than 0.01), compared with patients in the IDC group. To assess symmetry of contraction, a maximum difference score was derived for each patient. Symmetry (a score less than 1) was present in 5 IDC and no CAD patients, whereas asymmetry (a score of 2 or more) was present in 27 CAD and 7 IDC patients (p less than 0.01). Wall motion became more symmetric in both groups when LVEF was less than 0.20. Logistic regression analysis revealed that the maximum difference score was the best predictor of the diagnosis, but only because of better separation at the extremes of maximum difference score values.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4038572 TI - Ultrastructure of Sertoli-cell penetrating processes found in germ cells of the golden-mantled ground squirrel (spermophilus lateralis). AB - We have studied the ultrastructure of Sertoli-cell processes that extend into developing germ cells of the ground squirrel (Spermophilus lateralis). In other mammals it is speculated that these processes anchor germ cells to the seminiferous epithelium and transfer materials between Sertoli and germ cells. In the ground squirrel, Sertoli-cell projections first appear in round spermatids and consist of regions containing numerous mitochondria and intermediate filaments together with areas composed mainly of a fine filamentous matrix. Also present are what may be desmosomelike junctions with adjacent germ cells. During spermatogenesis, numerous changes in the penetrating processes and their internal composition occur. Especially significant are those occurring during the movement of residual cytoplasm basally over spermatid heads: some Sertoli-cell processes contain microtubules, mitochondria, and vesicular elements, but also present are regions that lack organelles and appear simply as thin lamellae of cytoplasm that line cavernous invaginations of the germ cell. Coated vesicles and pits are present in processes and adjacent germ-cell regions at all stages of spermatogenesis. Our observations are consistent with the suggestions that Sertoli-cell processes have an attachment function and that they also may facilitate the movement of residual cytoplasm into the epithelium. Further, they indicate that these structures might be involved with receptor-mediated edocytosis. PMID- 4038573 TI - Absorption and retention of selenium from intrinsically labeled egg and selenite as determined by stable isotope studies in humans. AB - A study was carried out with four healthy young adult men, consuming a self selected diet, to investigate quantitative aspects of the gastrointestinal absorption, urinary excretion, and body retention of egg selenium in comparison with selenite. The approach involved simultaneous consumption of egg biologically labeled (intrinsic) with the stable isotope 74Se and a dose of selenite labeled with 76Se (extrinsic label). Four labeled test diets, given on days 6, 16, 26, and 36 of the study were employed, each differing in their protein source: test diet I, 74Se-labeled egg white; diet II, 74Se-labeled egg yolk (high labeling dose) plus balanced L-amino acid mixture; diet III, 74Se-labeled egg yolk (low labeling dose) plus balanced amino acid mixture; and diet IV, balanced amino acid mixture extrinsically labeled with both 74SeO32- and 76SeO32-. The latter diet was included to assess the magnitude of any cross-isotope methodological bias. Fractional absorption (means +/- SEM) for Diet IV was 0.771 +/- 0.010 for the 74SeO32- and 0.656 +/- 0.021 for the 76SeO32- (ratio: 0.851 +/- 0.020); reflecting a small overall cross-isotope bias. Accepting the measurements made with 74SeO32- as the more accurate, experimentally determined values of absorption for the extrinsic tag were adjusted accordingly. The corrected absorption for these diets (% of dose) was (mean +/- SEM; first value for intrinsic label, second value for extrinsic label): diet I, 54.1 +/- 0.7 and 55.4 +/- 2.2; diet II, 76.7 +/- 0.8 and 83.0 +/- 1.8; diet III, 79.0 +/- 1.5 and 85.2 +/- 4.0.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4038574 TI - Use of aztreonam in the treatment of serious infections due to multiresistant gram-negative organisms, including Pseudomonas aeruginosa. AB - Aztreonam is a novel antimicrobial agent belonging to the monobactam class of antibiotics. It inhibits both beta-lactamase-producing and non-beta-lactamase producing aerobic gram-negative bacilli, but it has no activity against gram positive species or against anaerobic species. The efficacy of aztreonam in the treatment of infection in 76 patients and its safety in 87 patients was evaluated. The majority (91 percent) of patients had significant underlying disease, and 47 percent were critically ill. Aztreonam produced an overall clinical response of 86 percent, with 10 of 11 cases of bacteremia cured, including four due to Pseudomonas aeruginosa, seven of eight cases of pneumonia, and seven of nine episodes of osteomyelitis. Infections due to bacteria resistant to ampicillin, carbenicillin, cefazolin, cefamandole, cefoxitin, and gentamicin were cured. Although 15 of 18 patients with exacerbations of pulmonary infection due to P. aeruginosa showed clinical improvement, bacteriologic cure was not achieved, as has been noted with other drugs. Similarly, patients with major underlying structural abnormalities of the urinary tract showed early relapses of bacteriuria. Aztreonam combined with antistaphylococcal, antistreptococcal, or antianaerobic agents provided an alternative to aminoglycoside use in these non neutropenic patients. Administration of 1 or 2 g every eight hours yield serum bactericidal levels well in excess of 1:8 against all Enterobacteriaceae and some P. aeruginosa strains. There was a low incidence of adverse side effects, none serious. Overall, aztreonam is a useful alternative to the drugs available for use in hospital-acquired gram-negative infections and provides a chance for more directed therapy. PMID- 4038575 TI - Relapsing post-transfusion purpura. A preventable disease. AB - Post-transfusion purpura is an isoimmune disorder that can recur if unrecognized. A 56-year-old woman is described who had her third episode of post-transfusion purpura 17 years after her last exposure to the inciting antigen. Clinical and immunologic features are reviewed, and specific preventive measures are proposed. PMID- 4038576 TI - Aztreonam: a monocyclic beta-lactam antibiotic. PMID- 4038577 TI - Treatment of gram-negative infections with aztreonam. AB - Twenty-one patients with serious gram-negative infections were treated with aztreonam. Twenty of these were clinical and microbiologic cures; there was one clinical improvement with microbiologic persistence. No bacteria became resistant. Cure rates were: bone and joint (11 of 11); skin and soft tissue (six of six); pneumonia (two of two); perinephric abscess (one of one); and intra abdominal abscess (zero of one). The bacteria responsible for these infections included Pseudomonas aeruginosa (12), Serratia marcescens (two), Enterobacter gergoviae (three), Enterobacter aerogenes (two), Escherichia coli (one), Citrobacter diversus (one), and Hemophilus influenzae (one). Aztreonam was well tolerated. Significant serum glutamic-oxaloacetic transaminase/serum glutamic pyruvic transaminase elevations developed in three patients, but none was symptomatic and all resolved after therapy was stopped. Two patients in whom a rash developed were receiving other antibiotics (vancomycin and metronidazole), making the cause of the rash unclear. Diarrhea developed in a single patient with Pseudomonas osteomyelitis, who also was receiving cefazolin for Staphylococcus aureus superinfection of his decubitus ulcer. Aztreonam was highly effective against gram-negative bacilli, including P. aeruginosa. The only clear-cut side effect was an asymptomatic rise in serum glutamic-oxaloacetic transaminase/serum glutamic-pyruvic transaminase levels in three patients. PMID- 4038578 TI - Efficacy and safety of aztreonam versus tobramycin for aerobic gram-negative bacilli lower respiratory tract infections. AB - Aztreonam therapy was evaluated for the management of 80 patients with gram negative bacilli lower respiratory tract infections. Study results confirmed its efficacy and safety for this indication. PMID- 4038579 TI - Aztreonam plus clindamycin as therapy for pelvic infections in women. AB - Aztreonam, a new monobactam antibiotic with specific gram-negative aerobic activity, was used in combination with clindamycin in the treatment of 40 women with pelvic infection, including post-partum endometritis, pelvic inflammatory disease, and post-hysterectomy pelvic cellulitis. Clinical cure was achieved in 87 percent of patients. Failure was related to the limited gram-positive aerobic spectrum of clindamycin. All aerobic gram-negative enteric organisms were sensitive in vitro to less than 0.125 microgram/ml of aztreonam. PMID- 4038580 TI - Current state of infectious diseases--potential areas of directed therapy with aztreonam. AB - Gram-negative bacillary organisms have continued to be a major source of hospital infections. Beta-lactamase-producing species have rendered many older beta-lactam antibiotics impotent. Aztreonam is a monocyclic beta-lactam antibiotic that inhibits aerobic gram-negative bacilli, including beta-lactamase-producing species. The agent has been used in the treatment of infections due to Enterobacteriaceae and Pseudomonas aeruginosa. Potential areas of use of aztreonam are as sole therapy for urinary tract infections, gram-negative pneumonias, and bone and joint infections. It can be used in combination with other antibiotics as empiric therapy of respiratory, intra-abdominal, skin structure, and gynecologic infections. Aztreonam offers a new approach to the use of beta-lactam antibiotics. PMID- 4038581 TI - Lowered prealbumin levels in patients with familial amyloid polyneuropathy (FAP) and their non-affected but at risk relatives. AB - Amyloid fibrils in familial amyloid polyneuropathy, the familial (AF) form of systemic amyloidosis, are composed of the monomeric unit (14,000 MW) of prealbumin molecules. By radioimmunoassay, the serum level of prealbumin was measured in 25 patients from 12 different kinships with this dominantly inherited form of amyloidosis and 56 unaffected, but at risk, relatives from two of the kinships. Results were compared to prealbumin levels in normal individuals and patients with primary (AL) and secondary (AA) forms of systemic amyloidosis. Significantly lowered prealbumin levels were found in the AF patients (149.2 micrograms/ml) and their at risk relatives (169.0 micrograms/ml) when compared to normal individuals (232.9 micrograms/ml), AL patients (221.9 micrograms/ml) and AA patients (211.7 micrograms/ml). No abnormality was found in levels of retinol binding protein (RBP), which is carried by prealbumin, in the serum of either the AF patients or their relatives. The depressed prealbumin levels may indicate a structural variant molecular form, an extra hepatic synthesis or an abnormality in catabolism of this protein that is present prior to the clinical or histopathologic onset of the AF disease. PMID- 4038582 TI - X-linked dominant chondrodysplasia punctata: a case report and family studies. AB - Two major types of chondrodysplasia punctata have been delineated; a severe, recessively inherited, rhizomelic form and the less severe, dominantly inherited Conradi-Hunerman form. Clinico-genetic analysis of this latter form of CP uncovered a sub-group characterised by asymmetric involvement with linear or whorled skin patches of ichthyosiform erythroderma or atrophoderma, circumscribed cicatricial alopecia, asymmetrical cataracts and limb shortness. The mosaic pattern of the manifestations and the limitation of reported cases to females suggested an X-linked dominant gene which undergoes Lyonisation in the female and is lethal in the hemizygous male. We report on a family ascertained through a baby girl who had manifestations typical of the X-linked dominant form of CP and whose mother, 2 of 3 maternal aunts, and maternal grandmother all had less severe manifestations. The absence of male offspring for 3 generations and a history of 3 early miscarriages, along with the clinical variability in the affected females, provide further support for X-linked dominant inheritance of this disorder. PMID- 4038583 TI - Genetic epidemiology of twinning: a population-based study. AB - We report on kinship analysis of mothers with twins and a study of their ancestors and inbreeding. A pair-matched case-control design supports the analyses. Nearly as high a number of ancestors was found at the origin of cases as in control individuals. Study cases were less inbred than control subjects, but their kinship was higher, especially for unlike-sex twins born after age 30 years of mothers and, but less so, for like-sex twins born to mothers younger than 30 years. The results indicate a genetic origin of both types of twins and possibly a highly spread gene with dominant or co-dominant expression. PMID- 4038584 TI - Screening for sexual problems through a simple questionnaire. AB - Screening for sexual problems should be part of the medical assessment, but there is controversy on the best method to use. This study compared the yield of a simple questionnaire with that of a more detailed interview. Ninety-eight sexually active women (out of a total of 110) admitted on an elective basis to general gynecology wards were studied. Forty-six patients presented with a sexual complaint and 33 (33%) of these requested medical attention for the problem. In all cases, the simple questionnaire was as effective as the detailed inquiry in detecting a sexual problem. It is concluded that a simple questionnaire can be used effectively by all physicians as a screening test for sexual dysfunction with regard to heterosexual coital activity. Further research is required to confirm this hypothesis in other conditions of medical practice. PMID- 4038585 TI - The Marlex sling operation for the treatment of recurrent stress urinary incontinence: a 16-year review. AB - Between 1968 and 1983, 281 patients with recurrent stress urinary incontinence and nine patients with primary stress urinary incontinence were treated with a two-team (suprapubic vaginal) Marlex urethral sling operation. Selection was based on the patient's history and the clinical demonstration of an anatomic defect in the closure mechanism of the urethra. The operative technique as described in 1970 remains unchanged. The bladder neck is released from the scar and replaced in a midretropubic position on a hammock of Marlex mesh attached to Cooper's ligaments. Patients with a sloughed urethra had a sling operation in conjunction with the reconstruction of a neourethra. The overall success rate based on a minimum 5-year follow-up of 208 patients was 77.4%. There was a high failure rate in the sloughed urethra group. Significant overall complications include bladder neck obstruction and chronic cystitis. PMID- 4038586 TI - Argon laser photocoagulation for macular edema in branch vein occlusion. PMID- 4038587 TI - Stimulation of lipolysis in rat heart myocytes by isoproterenol. AB - Calcium-tolerant myocytes were isolated from rat hearts. Isoproterenol produced a dose-dependent increase in glycerol output (lipolysis) that could be blocked by propranolol. The presence of glucose in the incubation medium enhanced the release of glycerol from myocytes but had no effect on the decline in triacylglycerol content. No incorporation of radioactivity from [U-14C]glucose into glycerol could be detected. In incubations with isoproterenol, there was a stoichiometric relationship between the glycerol output and the decrease in triacylglycerol levels. The addition of the phosphodiesterase inhibitor 1-methyl 3-isobutylxanthine resulted in an increase in the basal glycerol output and an enhancement of the isoproterenol-stimulated lipolytic rate. Forskolin and 8-(4 chlorophenylthio)adenosine 3',5'-cyclic monophosphate also produced a concentration-dependent stimulation of lipolysis in myocytes. Therefore, lipolysis in isolated myocytes must be regulated by adenosine 3',5'-cyclic monophosphate-dependent mechanisms. These results demonstrate that lipolysis can be observed in myocardial cells and that the lipolytic response to isoproterenol cannot be secondary to a physiological (inotropic) response since these myocyte preparations are quiescent. PMID- 4038588 TI - Kinetic model for disposition of 6-mercaptopurine in monkey plasma and cerebrospinal fluid. AB - The antipurine 6-mercaptopurine (6-MP) is effective in the induction and maintenance of remission in patients with acute lymphocytic leukemia. This report presents a compartmental model that describes the kinetics of 6-MP in the plasma and cerebrospinal fluid (CSF) of the monkey. Analysis is based on simultaneously measured plasma and CSF 6-MP concentrations after intravenous and intraventricular bolus administration. Results indicate that 6-MP administered intraventricularly remains largely in the CSF. Disappearance of 6-MP from CSF is principally due to convective losses at a rate equivalent to CSF turnover. Diffusion of 6-MP across the ependymal surface accounts for only 7% of the 6-MP appearing in the plasma. Conversely the dominant route for entry of 6-MP into the CSF from the plasma is entrainment in choroidally formed CSF. Only 12% of 6-MP in the CSF after intravenous administration can be accounted for by permeation of cerebral capillaries and diffusion through brain parenchyma and across the ependymal surface into CSF. These results indicate that the choroid plexus is not a significant barrier for the transfer of molecules like 6-MP from plasma to CSF. PMID- 4038589 TI - Evidence for autosomal recessive inheritance in 46 families with multiple incidences of autism. AB - The authors ascertained 46 families with multiple incidences of autism (41 with two and five with three autistic probands). Classical segregation analyses revealed a maximum likelihood estimate of the segregation ratio of p = 0.19 +/- 0.07. This is not significantly less than 0.25, the expected value for autosomal recessive inheritance. However, it is significantly less than 0.50, the expected value for autosomal dominant inheritance. The polygenic threshold model was tested and rejected over a full range of values of heritability and ascertainment probability for these families. These results are most consistent with the hypothesis of autosomal recessive inheritance in this subset of 46 families with multiple incidences of autism. PMID- 4038590 TI - Evaluation of a purified Schistosoma japonicum glycoprotein egg antigen for the immunodiagnosis of infection in man. AB - A purified glycoprotein, glycoprotein-2, which was isolated from Schistosoma japonicum soluble egg antigen, was tested in an enzyme-linked immunoadsorbent assay for its potential as an immunodiagnostic reagent. Using empirically-derived criteria of endpoint titer, 39/40 sera from S. japonicum-infected individuals were scored correctly as positive in a blind test. Of these, 26/40 were from individuals who excreted fewer than 100 eggs per gram of stool. No cross reactions were observed with sera from uninfected individuals (0/20) or from individuals infected with S. mansoni (0/22), Trichinella spiralis (0/6) or Brugia malayi (0/4). Cross reactions were observed with 3/24 individuals infected with S. haematobium who excreted greater than 2,000 eggs per 10 ml urine. Glycoprotein 2 appears to satisfy the requisite criteria of specificity and sensitivity to warrant further evaluation. PMID- 4038591 TI - Ultrastructural heterogeneity of the basophilic cells in the allergic nasal mucosa. AB - Basophilic cells in scrapings and pieces of nasal mucosa removed from the inferior turbinates of adult patients with house dust nasal allergy plus pieces of the oral mucosa from normal persons were examined electron microscopically. Three distinct types of basophilic cells, ie, blood basophil leukocytes (predominantly in the subepithelium), mucosal mast cells (predominantly in the epithelium), and connective tissue mast cells (predominantly in the deeper lamina propria) were identified in the nose. PMID- 4038592 TI - Nitrous oxide sedation/analgesia in emergency medicine. AB - Nitrous oxide:oxygen mixtures are safe and effective sedative/analgesic agents for use in emergency medicine. They are suitable for prehospital care because of their safety, rapid onset, and short duration of action. The self-administered form of a 50:50 mixture is the most acceptable system, but other methods of administration should be investigated, particularly in the ED setting. While there are unresolved questions concerning the use of nitrous oxide as an anesthetic and analgesic agent, it is difficult to extrapolate many of the findings to the low-dose, patient-controlled 50:50 mixture used in emergency medicine. Use of the gas mixture in a variety of clinical settings has been associated with no major adverse occurrences, and experience continues to support its safety. Future possibilities for study include the use of the gas mixture in combination with other agents or TENS. No one drug can be considered a panacea for all painful states. Nitrous oxide:oxygen mixtures certainly do not meet all the criteria for the ideal analgesic. Those clinicians who seek a safe and effective sedative/analgesic for mild to moderate pain will be satisfied that we can now offer more to our patients in the early management of their problems. PMID- 4038593 TI - Effect of vitamin A deficiency on mammary gland development and susceptibility to mastitis through intramammary infusion with Staphylococcus aureus in mice. AB - Weanling mice were fed 0 or 150 micrograms retinol equivalent/kg of diet for 5 weeks, were bred, and allowed to complete gestation. On day 3 of lactation, all mice were separated from their litters for 1 hour and were then anesthetized. The 4th right or left mammary gland was inoculated with 0.1 ml of S Aureus (10(10) colony-forming units/0.1 ml). Exactly 24 hours after inoculation, the mice were euthanatized and the mammary glands were removed and fixed for histologic evaluations. Vitamin A-deficient dams had smaller litter size and lower liver stores of vitamin A; however, deficiency was not severe enough to produce external signs of vitamin A deficiency in the dams. Morphologic studies showed large areas of adipose tissue, greatly reduced ductal and lobule-alveolar development, and decreased total secretory activity in mammary glands from vitamin A-deficient females. On the other hand, mammary glands from vitamin A supplemented mice had extensive lobule-alveolar development and highly distended alveoli. Extensive necrosis of alveolar tissue was observed in staphylococcus infused mammary glands of all mice. Large numbers of leukocytes and cell debris were present in the lumen of alveoli and ducts. However, mammary glands from vitamin A-deficient females had more extensive pathologic damage compared with corresponding glands from vitamin A-supplemented mice. Results indicted that vitamin A-deficient mice had reduced mammary development and increased pathologic damage to the mammary gland after intramammary challenge with staphylococcus. PMID- 4038594 TI - Histopathology of otitis media in infants with cleft and high-arched palates. AB - The middle ear and the bony and cartilaginous portions of the eustachian tube (ET) were studied histopathologically in 20 temporal bones from 19 infants, aged 45 minutes to 12 months. Otitis media (OM) was observed in 17 of 20 bones, and 16 bones with OM had an effusion. Otitis media was more severe in the ears of cleft palate infants compared to those with high-arched palates. Inflammation was present in the bony portion of the ET in 15 of 17 temporal bones with OM, but appeared to be less marked than that present in the middle ear. In addition, inflammation of the cartilaginous portion of the ET appeared to be less severe than in its bony portion. Inflammation of the middle ear and the ET appeared to be more pronounced in older infants, particularly in those with cleft palates. PMID- 4038595 TI - Angiosarcoma of the larynx. Case report. AB - Angiosarcoma of the larynx is an uncommon malignant tumor of mesenchymal origin. A case of angiosarcoma of the epiglottis was followed for about 6 years. Diagnostic and clinicopathologic findings outline the importance of a correct differential diagnosis from other vascular malignant tumors (malignant hemangiopericytoma and Kaposi's sarcoma). A critical review of the literature is included. PMID- 4038596 TI - cis-Diamminedichloroplatinum-mediated crosslinking of nuclear proteins to DNA is cell cycle specific. AB - Immunochemical analysis was employed to investigate the cell cycle-dependent protein-DNA crosslinking by cis-diamminedichloroplatinum II (cis-DDP), in HeLa-S3 cells. Cells synchronized by double thymidine block or hydroxyurea were released into S phase and incubated at 2-h intervals with cis-DDP as they progressed through S1, G2, M, and then into G1 and S phases of the subsequent cycle. Immunoblots of the DNA-crosslinked antigens reacted with antisera to 0.35 M NaCl extract or residue of HeLa S-phase nuclei revealed that several antigens changed their DNA-crosslinking pattern during the progression of HeLa cells through their reproductive cycle. PMID- 4038597 TI - [Intra-arterial infusion chemotherapy for non-resectable pancreatic cancer using angiotensin-II and prostaglandin-E1]. AB - We have developed a new method of intra-arterial infusion chemotherapy for non resectable pancreatic cancer, in order to facilitate the selective delivery of a large amount of anticancer agent to the cancer lesion. This method was carried out as follows: (1) retrograde cannulation was performed by inserting a catheter into the splenic artery after splenectomy, and many of its branches were dissected out around the body and tail of the pancreas: (2) anticancer drugs (Adriamycin and Methotrexate) were infused together with Angiotensin-II to decrease the blood flow to non-malignant tissue and to increase the flow to cancer tissue. (3) Twenty-four to 48 hours after Methotrexate was infused, rescue was performed with an infusion of Prostaglandin-E1 to reduce the degree of cytotoxic damage to normal tissue. By using these methods, it was ascertained that a large quantity of the drugs had accumulated in the cancer tissue, even though its original blood flow had been established as very poor by radioisotope and angiographical examination. This therapy was useful not only for anticancer effects on the primary lesion but also the prevention of liver metastasis. Moreover, Methotrexate and rescue therapy were shown to have no remarkable side effects. PMID- 4038598 TI - Non-immunologic hydrops fetalis. PMID- 4038599 TI - Cryptosporidiosis. Traveler's diarrhea in two families. AB - Intestinal cryptosporidiosis was diagnosed in three infants (aged 6 to 21 months), one child (aged 3 years), and two adult members of two families after their return from travel to the African continent. Examination of stools from all patients revealed acid-fast cryptosporidial oocysts on direct fecal smears stained by the modified cold Kinyoun technique. Five of the six were symptomatic with watery diarrhea, anorexia, and abdominal pain. Elevated anticryptosporidial titers were detected in five patients, two of whom were asymptomatic. Cryptosporidiosis should be included in the differential diagnosis of traveler's diarrhea. PMID- 4038600 TI - Structure-activity relationships of atrial natriuretic factor (ANF). II. Effect of chain-length modifications on vascular reactivity. AB - The effect of the length of ANF peptides on the inhibition of the norepinephrine induced contraction was studied. Starting from the 26 residues ANF (Arg101 Tyr126), shorter N- and/or C-terminal fragments were produced, either by N terminal chemical cleavage or C-terminal enzymatic digestion of ANF or both respectively. The N-terminal removal of Arg101 did not modify the inhibitory response. Further N-terminal truncation up to des-Arg101-Arg102-Ser103-Ser104 ANF still produced a marked inhibitory effect on norepinephrine. In contrast C terminal cleavage had a much more pronounced effect. Since des-Tyr126 ANF, des Arg125-Tyr126 ANF and des-Phe124-Arg125-Tyr126 ANF exhibit much lower activities than the parent ANF. Finally, when the 5 residues C-terminal to Cys121 are removed, the resulting molecule is almost inactive. These data indicate that the C-terminal segment of ANF may modulate the binding of ANF to its receptor(s). Relatively, the N-terminal region seems to be much less important. PMID- 4038601 TI - Platelet cytoskeleton--membrane interactions. AB - The order of attachment of the purified platelet cytoskeletal proteins, F-actin, alpha-actinin and Actin Binding Protein (ABP) to the isolated platelet membrane has been investigated. Of the three proteins, only F-actin would directly interact with a membrane preparation that had been extensively washed to remove associated cytoskeletal proteins. alpha-Actinin would only add to the membrane to which F-actin had been re-attached and ABP only if both F-actin and alpha-actinin were present on the membrane. These studies provide some insight into the nature of the attachment of the platelet cytoskeleton to the cytoplasmic side of the membrane. PMID- 4038603 TI - [Posthemorrhagic hydranencephaly in the fetal period with deficiency of factor XIII (fibrin stabilizing factor)]. PMID- 4038602 TI - Attenuation of chick heart adenylate cyclase by muscarinic receptors after pertussis toxin treatment. AB - Pertussis toxin selectively modifies the function of Ni, the inhibitory guanine nucleotide binding protein of the adenylate cyclase complex. In chick heart membranes, guanine nucleotide activation of Ni resulted in a decrease in the apparent affinity of the muscarinic receptor for the agonist oxotremorine, inhibition of basal adenylate cyclase activity, and the attenuation of adenylate cyclase by oxotremorine. Treatment of chicks with pertussis toxin caused the covalent modification of 80-85% of cardiac Ni. After this treatment Gpp(NH)p had no effect on muscarinic receptor affinity and GTP stimulated basal adenylate cyclase activity. In contrast, the GTP-dependent attenuation of adenylate cyclase caused by muscarinic receptors was unaffected. PMID- 4038604 TI - Comparison of ventricular emptying with and without a pressure gradient in patients with hypertrophic cardiomyopathy. AB - Thirty three patients with hypertrophic cardiomyopathy were studied to determine whether the presence of an intraventricular pressure gradient impaired left ventricular emptying. Patients with resting gradients had a higher mean left ventricular ejection fraction (92 (6.4)%) than patients without a resting or inducible pressure gradient (75.5 (9)%). The rate and degree of emptying increased when gradients greater than 85 mm Hg were induced in two patients with insignificant mitral regurgitation. If the induced gradients had been the result of obstruction a decrease in the rate or degree of ventricular emptying would be expected. Higher ejection fractions in patients with intracavitary pressure gradients as well as enhanced rate and degree of left ventricular emptying with induced gradients are inconsistent with outflow obstruction. These findings support the concept that cavity obliteration is responsible for the pressure gradient in these patients with hypertrophic cardiomyopathy. PMID- 4038605 TI - Vitamin A and non-epithelial tumours. PMID- 4038606 TI - Anticardiolipin antibodies in autoimmune thrombocytopenic purpura. AB - Using a recently devised solid phase radioimmunoassay to detect anticardiolipin antibodies, we report the presence of these antibodies in 30 of 96 patients with chronic autoimmune thrombocytopenic purpura (AITP). IgG anticardiolipin antibody levels were elevated in 14 patients and IgM anticardiolipin antibody levels were elevated in 27 patients. We suggest that these antibodies may mediate peripheral platelet destruction by binding to phospholipids in the platelet membrane. It is also conceivable that the presence of anticardiolipin antibodies may select a subpopulation of patients with chronic AITP who may go on to develop other autoimmune disorders, such as systemic lupus erythematosus. PMID- 4038607 TI - Excessive testosterone secretion in pregnancy. Case report. PMID- 4038608 TI - Role of mevalonate-5-pyrophosphate decarboxylase in the regulation of chick intestinal cholesterogenesis. AB - The response to different dietary conditions of the enzymes responsible for the transformation of mevalonic acid to isopentenyl pyrophosphate has been studied for the first time in the small bowel of the chick to elucidate the role of these enzymes in the regulation of intestinal cholesterogenesis. Feeding a 2% cholesterol diet from hatching resulted in a small but significant inhibition of mevalonate-5-pyrophosphate decarboxylase, while mevalonate kinase and mevalonate 5-phosphate kinase remained unaltered. Similar results were obtained for the three enzymes when 13-day-old chicks fed a standard fat-free diet were switched to a 5% cholesterol diet. Starved chicks exhibited lower intestinal decarboxylase activity than chicks fed a standard diet, while refeeding resulted in levels of activity similar or slightly greater than controls. None of the enzymes effecting the conversion of mevalonate to isopentenyl pyrophosphate in the small intestine presented diurnal variations. Results obtained suggest that mevalonate-5 pyrophosphate decarboxylase may play a significant role in the regulation of cholesterol synthesis in the small intestine. PMID- 4038609 TI - Inhibition of pregnancy with indomethacin in mature gilts and prepuberal gilts induced to ovulate. AB - Twenty prepuberal (P) gilts, 56.5 +/- 1.1 kg body weight, were induced to ovulate with 1000 IU of pregnant mare's serum gonadotropin followed 72 h later by 500 IU of human chorionic gonadotropin (hCG), and bred by artificial insemination (AI) with 50 ml fresh pooled boar semen the day after hCG treatment (Day 0). Eighteen mature (M) gilts, 120.6 +/- 1.7 kg body weight, were bred by AI each day of estrus using pooled semen from the same boars (onset of estrus = Day 0). One-half of each group was fed the prostaglandin (PG) synthesis inhibitor indomethacin (IND), at 10 mg/kg body weight, or control (C) feed twice daily on Days 10 to 25. Blood samples taken by venipuncture on Days 10, 15, 20 and 25 were quantitated for progesterone (P4) and 13,14-dihydro-15-keto-PGF2 alpha (PGFM) by radioimmunoassay. Ovaries were examined on Day 26. All M-C gilts were pregnant, whereas 3 of 9 M-IND gilts (P less than 0.05) and none of the P gilts (P less than 0.01) were pregnant. Three of the 6 nonpregnant M-IND gilts displayed estrus on Day 21. The 3 remaining M-IND gilts had maintained corpora lutea (CL) on Day 26. Only corpora albicantia were present in P gilts on Day 26. Serum P4 concentrations for M-C gilts, nonpregnant M-IND gilts with maintained CL, and pregnant M-IND gilts were not different. Serum P4 for all nonpregnant gilts in which CL had regressed by Day 25 decreased to less than 5 ng/ml on Day 20.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4038610 TI - Immunohistochemical studies on the localization of cellular retinol-binding protein in rat testis and epididymis. AB - The immunohistochemical localization of cellular retinol-binding protein (CRBP) was studied in rat testis and epididymis. Parallel studies were also carried out on the localization of plasma retinol-binding protein (RBP) and transthyretin (TTR) in testis. The studies employed antibodies purified by immunosorbent affinity chromatography, permitting the specific staining and localization of each antigen by the unlabeled peroxidase-antiperoxidase method. For RBP and TTR, specific immune staining was found in the interstitial spaces between the seminiferous tubules, and not in the tubules themselves. In contrast, strong specific immune staining for CRBP was found in the seminiferous tubules, with a striking localization within Sertoli cells. Moreover, a distinct cyclic variation of specific staining for CRBP within Sertoli cells was observed during the spermatogenic cycle. This cyclic variation was seen with regard to both the intensity of staining and to the anatomic distribution of CRBP within the Sertoli cells. Within the epididymis CRBP was selectively localized to the proximal portion of the caput epididymidis, with variations in intensity of the staining of the epithelium of the ducts in different histological zones. Specific immune staining for CRBP was very weak or absent in the other portions of the epididymis. These results were confirmed by radioimmunoassay. Vitamin A-deficient rats showed markedly reduced specific immune staining for CRBP in both testes and epididymides, and greatly reduced levels of CRBP in these tissues on radioimmunoassay. These studies on the localization of CRBP provide information concerning the specific cells and anatomic loci within the testis and epididymis where retinol may be playing an important role in sperm formation and maturation. PMID- 4038611 TI - [Enhancement of the immune response to surface antigens of the influenza B virus as a result of their covalent binding with a synthetic polymer carrier]. AB - The primary immune response (the number of antibody-forming cells, AFC) and the delayed type hypersensitivity (DTHS) were studied in mice immunized either with isolated glycoproteins of influenza virus (hemagglutinin, HA and HA plus neuraminidase, HA plus NA) or with their conjugates with an acrylic acid copolymer (CP) and N-vinylpyrrolidone of equimolar composition. Immunization of mice with conjugates containing virus proteins (virogates-HA-CP or HA plus NA-CP- entailed a 50-100 increment of the number of IgM- and IgG-AFC, anti-HA as compared with analogous parameters during immunization of animals with isolated virus proteins. Immunization of mice with the virogate HA-CP gives rise to the development of a more pronounced DTHS to HA. The authors discuss the possibility of the use of this basically new approach to the design of highly immunogenous vaccine preparations, effective in the control of influenza and other virus diseases. PMID- 4038612 TI - [Modifying action of neonatal androgenization on 1,2-dimethylhydrazine-induced carcinogenesis in male CBA-strain mice]. AB - Newborn male CBA mice received a single treatment with 0.5 mg testosterone propionate. Weekly subcutaneous injections of 1,2-dimethylhydrazine (DMH) were given to 2-month-old mice. The incidence of pararenal angiosarcomas and colonic tumors in neonatally androgenized mice reached 78.5 and 71.0%, respectively by the 35th week after the DMH treatment was commenced. In DMH-treated control mice, the incidence of the above tumors amounted to 25 and 32%, respectively. PMID- 4038613 TI - Catabolism of human tissue plasminogen activator in mice. AB - The catabolism of human tissue plasminogen activator (t-PA) was studied in mice. The clearance of t-PA labeled with iodine 125 was rapid (t1/2). The clearance of phenylmethylsulfonyl-125I-t-PA, which is active site-inhibited, was identical to the active enzyme. Sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS PAGE) demonstrated that the vast majority of 125I-t-PA injected into the circulation was present as free enzyme and not in a complex with inhibitors. The clearance of 125I-t-PA was unaltered by large molar excesses of several ligands of known clearance specificities, including macroalbumin, asialoorosomucoid, and diisopropylphosphorylthrombin and was also not altered in the presence of a 1,000 fold molar excess of unlabeled t-PA. Organ distribution studies demonstrated that the early rapid clearance of 125I-t-PA occurred in hepatocytes, followed by a later renal phase of clearance. The clearance of 125I-urokinase (UK) also was studied and was very similar in all aspects to the clearance of 125I-t-PA. These results suggest that both t-PA and UK are cleared from the circulation by unique nonsaturable processes localized in the liver that are independent of the proteinase active site. PMID- 4038614 TI - Platelet kinetics in patients with idiopathic thrombocytopenic purpura and moderate thrombocytopenia. AB - We studied ten normal subjects and 20 patients with stable, untreated idiopathic thrombocytopenic purpura (ITP) and platelet counts in the range of 35,000 to 110,000/microL. The diagnosis was made by clinical criteria. Platelet-associated IgG was increased in all nine of the nine patients studied. Autologous platelets were labeled with chromium 51 and reinfused for measurement of mean cell life and platelet production rate. Mean cell life was calculated by two methods, weighted mean and multiple hit, with excellent agreement between the two. As expected, mean cell life was significantly reduced in ITP patients as compared to the normal subjects (2.9 days v. 8.0 days, P less than .001). However, mean platelet production rates in ITP patients and normal subjects, 3.5 and 3.8 X 10(9) platelets/k/d respectively, were not significantly different. Platelet production rate was above and below the normal range (2 to 5.6 X 10(9) platelets/k/d) in two and four patients, respectively. We conclude that the rate of platelet production is not increased in most patients with ITP who have platelet counts greater than 35,000/microL. We did find that platelet size was increased in eight of the 12 patients in whom it was measured, including two of the patients with low platelet production. PMID- 4038615 TI - Regulation of erythropoiesis in long-term hamster marrow cultures: role of bone marrow-adherent cells. AB - The initial establishment of hamster long-term bone marrow (LTBM) cultures requires formation of an adherent stromal layer, but continued long-term proliferation of these cultures is best accomplished by removal of the suspension cells from the adherent layer and subsequent incubation in liquid suspension culture. Continued maintenance of bone marrow cells in the presence of the adherent layer for more than four to six weeks leads to a decline and eventual disappearance of erythroid and multipotent colony-forming cells. Addition of erythropoietin to LTBM suspension cultures produces mature, hemoglobinized erythrocytes. Incubation of the same cells plus erythropoietin in the presence of autologous parental adherent layers markedly inhibits both terminal erythroid differentiation and the number of detectable erythroid burst-forming units (BFU Es). This erythroid inhibition occurs primarily within the first 24 hours with little or no effect on CFU-GEMMs or granulocyte-macrophage colony-forming units (GM-CFUs). However, continued incubation for seven days produces a reduction in all parameters. Removal of suspension cells from the adherent layer and restimulation with erythropoietin allows regeneration of erythropoiesis. Pretreatment of suspension cells with erythropoietin for 96 hours before exposure to the adherent culture only slightly inhibits erythropoiesis, suggesting that more mature erythroid progenitors are unaffected. Conditioned medium from the marrow adherent layer (ALCM) produces similar erythroid inhibitory effects in LTBM cultures with as little as two hours of incubation. The inhibition is actively produced by the adherent cells, since cycloheximide abolishes its production, while indomethacin has no apparent effect. Adherent marrow stromal cells may regulate hemopoiesis through negative as well as positive humoral signals, and they are particularly effective in erythroid regulation. PMID- 4038616 TI - Effects of the menstrual cycle on medical disorders. PMID- 4038617 TI - Female chronic urinary retention. AB - Thirty-seven cases of female chronic retention are reviewed. Only 13 patients had neurological disease. The problems encountered in diagnosis and management are presented. PMID- 4038618 TI - Abnormal electromyographic activity (decelerating burst and complex repetitive discharges) in the striated muscle of the urethral sphincter in 5 women with persisting urinary retention. AB - In five women with urinary retention, recordings from the striated muscle of the urethral sphincter revealed highly abnormal electromyographic (EMG) activity. Using a concentric needle electrode, recordings revealed very striking bursts of activity, referred to here as decelerating burst (DB) and complex repetitive discharges (CRD). Such EMG activity is exceedingly unusual in skeletal striated muscle and resembles most closely the rarely encountered condition of "pseudomyotonia". We suggest that this abnormal activity is associated with a failure of relaxation of the striated muscle of the urethral sphincter, which results in chronic retention. PMID- 4038619 TI - Potential use of ultrasound in place of X-ray fluoroscopy in urodynamics. AB - A moving picture can be obtained using an ultrasonic scanning probe in the rectum to provide information about the bladder and urethra in the same projection as for lateral cystography. The method has potential as a substitute for cinecystography but there are a number of problems still to be overcome. PMID- 4038620 TI - Site of interaction of serotonin and desglycinamide-arginine-vasopressin in maintenance of ethanol tolerance. AB - Rats trained to walk in a moving belt apparatus were subjected to a partial (fornix-fimbria (FF] or total (fornix-fimbria + cingulum bundles (FF + CB] chemical denervation of the dorsal serotonergic afferent pathways to the hippocampus. After chronic alcohol treatment that resulted in tolerance development to the motor-impairing effects of ethanol, desglycinamide-arginine8 vasopressin (DGAVP) or saline treatment was started and the residual tolerance measured at several intervals after ethanol withdrawal. DGAVP administration resulted in a virtually complete retention of ethanol tolerance when given to sham-operated controls or FF-lesioned rats. The peptide treatment failed, however, to prolong tolerance in rats bearing a complete FF + CB lesion, that reduced serotonin (5-HT) levels in the hippocampus and overlying parietal cortex to 10 and 45% of controls respectively. These results suggest that the serotonergic innervation of these areas is necessary for the action of DGAVP in the maintenance of ethanol tolerance. PMID- 4038621 TI - Chronic phenytoin and the stereotyped motor response induced by 5-methoxy-N,N dimethyltryptamine in rats. AB - Male Sprague-Dawley rats were injected with phenytoin (PHT) once a day for 20 consecutive days and then tested as to their response to 5-methoxy-N,N dimethyltryptamine (5-MDMT), a 5-hydroxytryptamine (5-HT) agonist, at 1 and 3 mg/kg on days 21 and 28. It was found that long-term PHT administration decreased the intensity of a stereotyped motor response induced by 5-MDMT (3 mg/kg) on day 21 but not on day 28. A single injection of PHT (25 mg/kg) did not modify the motor response induced by 5-MDMT (3 mg/kg) on day 21 but not on day 28. A single injection of PHT (25 mg/kg) did not modify the motor response induced by 5-MDMT (1.7, 3.2 mg/kg). It is suggested that PHT increases the functional availability of 5-HT before its receptors, and thereby causes 5-HT receptor subsensitivity. PMID- 4038622 TI - Acute morphine treatment and morphine tolerance/dependence alter immunoreactive oxytocin levels in the mouse hippocampus. AB - Immunoreactive oxytocin levels were measured in the mouse hippocampal tissue (h OXT). Acute morphine treatment increased h-OXT, which effect was reversed by naloxone. In mice rendered tolerant to and dependent on morphine h-OXT was lower than in placebo pellet-implanted control mice. In the tolerant/dependent animals naloxone resulted in precipitated withdrawal syndrome which was associated with a slight increase in h-OXT. The data indicate that h-OXT is affected by acute morphine treatment and by morphine tolerance/dependence and raises the possibility that h-OXT participates in the adaptive response of the organism towards narcotic drugs. PMID- 4038623 TI - [Splenectomy for idiopathic thrombopenic purpura. A retrospective study of 40 cases]. AB - The authors analysed retrospectively the files of 40 patients who underwent splenectomy for idiopathic thrombocytopenic purpura and who were totally or partially (relapse) resistant to a therapeutic trial of corticosteroids. There was no operative mortality but morbidity, especially respiratory, was substantial, being 40%. Drainage of the splenic bed should be avoided because this is clearly associated with a greater frequency of pulmonary complications. In 37 patients with a mean follow-up of 30.3 months, there was complete remission in 89.2% after splenectomy. This confirms the therapeutic value of splenectomy in idiopathic thrombocytopenic purpura, especially in those who showed a partial (transitory) response to corticosteroids. PMID- 4038624 TI - Anxiety, fears and depression related to hysterectomy. AB - One-hundred and two women undergoing a hysterectomy for reasons other than cancer were interviewed pre-operatively. Fifty-three of them filled out the Spielberger State and Trait Anxiety Scale (STAI). Women who had high anxiety scores were more likely to be depressed, both before and after the operation. Depression occurred also more often in women who had emergency hysterectomies and in women who had expressed, pre-operatively, some fears of possible change in their sexual life after the operation. PMID- 4038625 TI - Flow cytometric studies on modulation of cellular adriamycin retention by phenothiazines. AB - Phenothiazines (chlorpromazine and trifluoperazine) enhance the cellular retention and cytotoxicity of adriamycin in P388/S and P388/R cells. Effects on the resistant cells are more pronounced than those on the sensitive cells. Multiparametric flow-cytometric determination of cellular Adriamycin fluorescence shows that the phenothiazine effects are not uniform in a cell population, and cells in later part of the cell cycle traverse (S and G2/M), mitogen-stimulated lymphocytes (as compared to nonstimulated lymphocytes), and ascites (as compared to splenocytes) have greater sensitivity to phenothiazine effects on Adriamycin retention. PMID- 4038626 TI - Intracavitary cisplatin chemotherapy for mesothelioma. AB - A feasibility study of intracavitary cisplatin was conducted in eight patients with mesothelioma. Cisplatin, 90 mg/m2, was instilled weekly for 3 weeks, followed by a 3-week rest; thiosulfate was given iv to reduce nephrotoxicity. In 50 courses there was no chemical serositis; the major toxic effect was myelosuppression. One patient with measurable disease had a complete response; three others had objective responses. PMID- 4038627 TI - On the role of microfilaments in cell-shape-mediated growth control of lens epithelial cells. AB - With regard to the fact that, in anchorage-dependent lens epithelial cells, DNA synthesis can be switched on and off by cell flattening and cell rounding, respectively, the state of the microfilaments has been followed by labelling actin with FL-phalloidin during cell-shape alterations. Cell flattening proved to be accompanied by both a structural organization of actin filaments into stress fibres and an enlargement of the area of the cell nucleus. Cell rounding, on the other hand, caused the microfilament bundles to disappear and the area of the nucleus to become smaller. From the time course of the inhibition of DNA synthesis by cytochalasin B, it was inferred that functionally intact microfilaments are required for the entrance of the cells into DNA synthesis but not for the maintenance of ongoing DNA synthesis. The assumption has been made that the tension, generated by microfilaments during cell spreading, will affect the state of the plasma membrane as well as the shape and the structure of the nucleus, which in turn seems to be preparatory for cells to enter the cycle. PMID- 4038628 TI - Testicular morphology and cell proliferation kinetics of immature germ cells and Sertoli cells in suckling undernourished rats. AB - Undernutrition during suckling was induced in newborn rats by increasing the litter size to sixteen pups to be fed by one mother. Animals reared in litters of eight served as controls. Undernourished animals showed retarded body and testicular growth during a suckling period of 22 days. Sequential morphogenesis of the testis was not altered up to 15 days of age. However, certain morphological alterations in Sertoli cells and Leydig cells were observed from 15 days onwards. Cell generation cycle of spermatogonial germ cells and supporting cells (future Sertoli cells) on day 9 showed marked prolongation of DNA synthetic phase (S), unaltered post-DNA synthetic phase (G2) and total cycle (Tc) and shortening of the pre-DNA synthetic phase (G1) indicating a depression in DNA synthesis in undernutrition. PMID- 4038629 TI - The hierarchy of requirements for an elevated intracellular pH during early development of sea urchin embryos. AB - The intracellular pH (pHi) rises 0.3-0.5 units after fertilization of sea urchin eggs, and this and previous work show this pHi change is necessary for initiating the developmental processes leading to cell division. The experiments described here reveal that while the elevated pHi is permanently required for a normal early development, lowering pHi of embryos after fertilization affects different processes to different extents. Protein synthesis gradually becomes less sensitive to pHi. Karyokinesis proceeds to completion under a low pHi, but is retarded, while cytokinesis is always impaired. These results indicate a hierarchy of requirements for high pHi during early development of sea urchin embryos, with protein synthesis, karyokinesis, and cytokinesis showing, respectively, increasing requirements for an elevated pHi. PMID- 4038630 TI - [The detrusor coefficient and the transmission factor in the diagnosis of incontinence]. PMID- 4038631 TI - [Physiology and pathophysiology of urination]. PMID- 4038632 TI - Thrombolytic therapy in patients with acute myocardial infarction. PMID- 4038633 TI - Specific anti-erythrocyte focus formation as a measure of autoantibody secreting cells in NZB mice. AB - Using a modification of the antibody forming cell (AFC) focus assay, it is possible to quantitate the spontaneous anti-erythrocyte autoantibody response of New Zealand Black (NZB) mice at the level of the autoantibody secreting cell. This complement independent assay is specific for an antigen(s) present on unmodified mouse erythrocytes. A comparison with the direct Coombs' test showed that the focus assay detected autoantibody responses earlier and demonstrated a wide range of AFC levels in responding mice. The focus assay provides a method for evaluating autoimmunity at the cellular level and for investigating the activities of cells responding to autoantigens. PMID- 4038634 TI - In vivo turnover studies of C-reactive protein. AB - The in vivo plasma clearance rate of the acute phase reactant C-reactive protein (CRP) was studied in mice and rats. The clearance rate of 125I-human CRP in mice and 125I-rat CRP in rats showed a T1/2 of approximately 4 h. The T1/2 was independent of circulating levels of CRP and was not affected by the presence of C-polysaccharide (CPS), a ligand to which CRP binds. However, in mice receiving sufficient CPS, more radioactivity localized to the spleen compared to mice receiving 125I-CRP only. 125I-CPS was rapidly cleared at the same rate by normal mice and by mice undergoing an acute phase response while rats cleared 125I-CPS more slowly despite having high circulating CRP concentrations. These findings suggest that CRP does not provide a mechanism for extremely rapid clearance of its ligands from the circulation, although the handling and subsequent fate of these ligands may be affected. PMID- 4038635 TI - Pharmacokinetics of aztreonam in patients with chronic renal failure. AB - The elimination kinetics of aztreonam (SQ 26,776), a new, completely synthetic, monocyclic beta-lactam antibiotic, were studied after the administration of a single 1g intravenous dose. Five healthy volunteers and 20 patients with various degrees of renal insufficiency were enrolled in this study. Concentrations of aztreonam in serum and urine were determined by both microbiological and high pressure liquid chromatography (HPLC) assays. The pharmacokinetic parameters for aztreonam were calculated on the basis of a 2-compartment open model. Serum concentrations of aztreonam at 10 minutes after administration were approximately 100 micrograms/ml in all subjects, regardless of renal function (HPLC assay). The mean serum half-life during the alpha-phase showed no important variation with renal function. The mean serum half-life during the beta-phase was 1.8 hours in normal subjects and 8.4 hours in haemodialysis patients (HPLC assay). There was a linear correlation between the serum clearance of aztreonam and creatinine clearance. The mean cumulative urinary recovery of aztreonam in 48 hours was 60 to 70% of the administered dose in normal subjects but this was reduced in the presence of renal insufficiency. SQ 26,992, the microbiologically inactive metabolite of aztreonam resulting from hydrolytic opening of the beta-lactam ring, was undetectable in the serum of normal subjects but was found in low levels in uraemic patients. Half of a 1g intravenous dose of aztreonam was eliminated during 4 hours of haemodialysis. Guidelines for administration of aztreonam in the presence of renal failure are given. PMID- 4038636 TI - Skin capillary blood cell velocity in patients with arterial obliterative disease and polycythaemia: a disturbed reactive hyperaemia response. AB - Nailfold skin capillary blood cell velocity (CBV) was studied at rest and during post-occlusive reactive hyperaemia after a 1 min arterial occlusion (PRH1) in: (i) both hands of patients with arterial obliterative disease (AOD) of one arm, (ii) patients with polycythaemia, before and after a moderate haemodilution and (iii) healthy controls. CBV was analysed by videophotometric cross-correlation utilizing the different optical densities produced by the passage of erythrocytes, leucocytes and plasma gaps through the monitored capillary. Resting CBV in the patients with unilateral AOD was similar in equivalent fingers of both hands. However, the time to peak (p)CBV during PRH was significantly prolonged in the low-pressure arm as compared to the contralateral arm. pCBV was also delayed in the patients with polycythaemia as compared to the healthy controls. This delay was not affected by the replacement of 500-750 ml of blood with the same amount of a 6% Dextran 70 solution. The mean capillary blood cell velocity during rest (rCBV) did not differ between controls and patients before or after the haemodilution. The prolonged time to pCBV in the polycythaemic patients may be attributed to increased blood viscosity that is presumably not significantly influenced by a moderate haemodilution using Dextran 70. The marked delay to pCBV observed distal to the arterial obstruction in patients with AOD probably is an effect of the lower arterial pressure, presumably involving an alteration of vascular smooth muscle function. PMID- 4038637 TI - Plasma 3-methylbutanal in man and its relationship to hepatic encephalopathy. AB - 3-Methylbutanal is a volatile aldehyde which in the rat is derived, at least in part, from colonic bacterial breakdown of leucine. It has been proposed as a toxin of importance in the pathogenesis of hepatic encephalopathy in man. A rapid, reliable and highly reproducible method for estimating 3-methylbutanal in plasma is described using a gas-chromatograph with a head space-sampler. The mean plasma 3-methylbutanal concentration in non-fasting patients with hepatic encephalopathy, 0.244 mumol/litre (range 0-1.30) was not significantly different from the mean value in controls, 0.116 mumol/litre (0-0.349). Oral leucine feeding resulted in significant increases in plasma 3-methylbutanal concentrations in both control subjects and patients with cirrhosis. Peak leucine and 3-methylbutanal values occurred at approximately the same time and usually within 120 min of leucine ingestion. Pre-treatment with neomycin had no effect on the results of leucine feeding. No changes occurred in the clinical condition or psychometric performance of patients with cirrhosis fed leucine despite increases in plasma 3-methylbutanal of up to 700% over basal values. In man plasma 3 methylbutanal, at least in part, derives from ingested leucine independently of the action of colonic bacteria. The role of this compound in the pathogenesis of hepatic encephalopathy in man needs further exploration. PMID- 4038638 TI - The effectiveness of local injections of vasodilating agents to produce vasodilation in subcutaneous tissue in rabbits. AB - The isotope washout method has been widely used to study characteristics of the microcirculation in localized vascular beds. Some of these studies have used local injections of vasodilating agents to maximally dilate the vascular bed. This study was undertaken to determine the agent most effective in producing this critical vasodilation. A rabbit model was constructed that allowed the study of the subcutaneous blood flow by either 133Xe and 131I-antipyrine washout. Dose response curves were constructed for five agents. The agents used and the doses that produced the maximum washout rate, were histamine (100 micrograms), verapamil (0.5 mg), prostaglandin E1 (6 micrograms), papaverine (5 mg) and nitroprusside (60 micrograms). The five agents at these doses were compared with each other, and nitroprusside produced a greater washout rate than papaverine (P less than 0.005), histamine (P less than 0.001) and verapamil (P less than 0.005). There was no difference between nitroprusside and prostaglandin E1 (P greater than 0.01). The effect of three of the agents in producing tissue oedema was examined by comparing the washout rates values obtained with the two isotopes. Both nitroprusside and papaverine produced large oedema whereas histamine resulted in little oedema formation. Nitroprusside, therefore, appears to be the most suitable vasodilating agent for use in studies which require maximum vasodilation of localized vascular beds. PMID- 4038639 TI - Quantification of heart valve regurgitation: a critical analysis from a theoretical and experimental point of view. AB - A theoretical analysis is presented regarding factors of importance for the determination of distance of intrusion of the regurgitant jet in heart valve regurgitation. The analysis is based on hydrodynamic theory. In the idealized model situation, for a circular hole, the intrusion of the regurgitant jet is linearly related to the product of the fluid mean velocity in the orifice and the diameter of the orifice. This was also shown to be true in an experimental fluid model. Thus, volume regurgitation cannot be quantified by the measurement of distance of intrusion of the regurgitant jet alone. On the other hand, an estimate of volume regurgitation can, in the idealized situation, be obtained if mean fluid velocity in the orifice, distance of intrusion of the jet and regurgitation time are known. PMID- 4038640 TI - Antitumour activity of some platinum compounds. AB - A group of cis-ethylenediammine platinum (II) complexes were synthesized and their activity against Sarcoma-180 ascites tumour cells in mouse was tested. One of the compounds, Pt(HOCH2CH2NHCH2CH2NH2)Cl2, showed significant antitumour activity having little toxicity to the host. Like the parent compound, cis-DDP, it binds to DNA, but transcription is not the primary process inhibited by these compounds. The drug-DNA complex, though less toxic, was not more effective than the free drug. PMID- 4038641 TI - Treatment of the rabbit V-2 carcinoma with intralesional cisplatin. AB - New Zealand white rabbits were used in the evaluation of intralesional injections of cisplatin for the management of experimentally induced V-2 carcinomas. The tumors were implanted into the right hip by intramuscular injections of an inoculum containing freshly harvested V-2 fragments which gave rise to a single, spherical mass (2-3 cm) 2 weeks after inoculation. All rabbits received two courses of either intralesional cisplatin or saline beginning 2 weeks after inoculation. Cisplatin injections significantly slowed the growth and spread of the primary tumor in all treated rabbits. In addition, intralesional chemotherapy prevented the development of lung metastases in 71% of the animals and produced approximately a threefold increase in survival time. Results indicate that not only is cisplatin active against experimentally induced V-2 carcinomas in rabbits, but direct intralesional injection is also an easy and effective means of administering chemotherapy. PMID- 4038642 TI - Visual function after pan-retinal photocoagulation: a survey. AB - Thirty-five diabetic patients who had undergone pan-retinal photocoagulation were surveyed to determine the frequency and severity of visual difficulties they experience. Among the most frequent problems were difficulty adjusting to dim lighting, difficulty adjusting to bright lighting, and trouble in sorting dark colors. Judging distances, negotiating stairways, and avoiding obstacles were identified as having become more difficult since the laser treatment. According to a correlation analysis, the difficulties encountered in some important tasks, such as driving in the daytime, were highly related to visual acuity. However, many of the problems reported most frequently, and many of the problems whose frequency had increased the most since the laser therapy, were not related to acuity. Despite their many visual complaints, the patients expressed very positive attitudes toward the photocoagulation treatment. PMID- 4038644 TI - Hospital intravenous drug administration in the era of prospective payment. AB - Cost effectiveness in all aspects of hospital care is necessary for survival in the 1980s. Under the new prospective payment system, the emphasis will switch from selling at a profit to increasing profits by spending less. Pharmacists need to reexamine available alternatives and new horizons in each area of distributive services, especially in the way we dispense and administer intermittent intravenous drugs. Manufacturer's piggyback containers are readily available for about 60 percent of required doses, and significant cost savings could result in a relatively short period of time. Newer systems that use syringes should also be explored and an in-hospital evaluation program set up to decide which is the most cost-effective, acceptable system. PMID- 4038643 TI - The antiemetic activity of droperidol administered by intramuscular injection during cisplatin chemotherapy: a pilot study. AB - The antiemetic activity of escalating doses of droperidol was evaluated in ten patients undergoing chemotherapy with cisplatin regimens. Major antiemetic activity was achieved in five patients, two patients had less nausea and vomiting as compared with prior prochlorperazine therapy, and three patients were refractory to droperidol. No dose-response relationship was observed. Sedation occurred in nine patients, and two patients experienced dystonic reactions. Droperidol is a relatively safe and effective antiemetic for patients undergoing chemotherapy with cisplatin. PMID- 4038645 TI - Vasoactive intestinal peptide is a physiological mediator of prolactin release in the rat. AB - To determine whether VIP functions as a physiological PRL-releasing factor, the effects of immunoneutralization of endogenous vasoactive intestinal peptide (VIP) on the PRL secretory response to suckling and ether stress were assessed. Using a porcine VIP-thyroglobulin conjugate as antigen, a peptide-specific antiserum was generated in a rabbit which bound porcine VIP with a Kd of 5.1 X 10(-11) M and a maximum binding capacity of 1830 ng/ml. In a RIA, this antiserum demonstrated immunoreactive VIP in tissue extracts of various regions of the brain and gastrointestinal tract. IR VIP in extracts of cerebral cortex and hypothalamus coeluted with synthetic porcine VIP on Bio-Gel P-30 column chromatography. Using chronically implanted right atrial catheters for blood sampling to avoid effects of stress and anesthesia, PRL blood levels in normal controls began to rise almost immediately after initiation of suckling from basal values of 3.0 +/- 0.9 ng/ml to reach a plateau of 158.1 +/- 33.5 ng/ml after 40 min. When the VIP antiserum was administered immediately before initiation of suckling, the onset of the PRL response was delayed by 40 min, but PRL levels then rose at a slower rate to reach the plateau level of normal animals approximately 80 min later. When VIP antiserum was administered to rats who had been suckling for at least 1 h, PRL levels fell from a mean basal elevated level of 152.7 +/- 16.0 ng/ml to a nadir of 50.4 +/- 9.1 ng/ml 80 min after injection and then gradually returned to basal levels. The effect of VIP antiserum was studied in rats in whom PRL secretion was increased by exposure to ether, a stimulus that acts on the release phase of PRL secretion. In rats in whom the depletion-transformation of PRL was induced by a prior brief period of suckling, subsequent exposure to ether caused a rise in serum PRL levels. The response was completely blocked in rats given VIP antiserum, whereas animals given nonimmune serum showed a significant increase in serum PRL to 38.6 +/- 17.3 ng/ml. We conclude from these studies that VIP mediates the acute PRL response to suckling and is required for maintenance of PRL levels in continuously suckling animals but is not the only factor causing PRL elevation. Complete abolition by the VIP antiserum of the PRL response to ether indicates that the effect of the anesthetic is mediated entirely by the release of VIP. These findings are consistent with the view that VIP is a physiological PRL-releasing factor in the rat. PMID- 4038646 TI - Lack of ovarian steroid negative feedback on pulsatile luteinizing hormone release between estrus and diestrous day 1 in the rat estrous cycle. AB - The object of this study was to determine the roles of ovarian estradiol (E2) and progesterone (P) in regulating pulsatile LH release between estrus and diestrous day 1 (D1) in the rat estrous cycle. Three groups of rats were bled at rates of 75 or 100 microliter whole blood/6 or 8 min, respectively, between 0930-1230 h on estrus or 24 h after either sham ovariectomy (OVX) on estrus (i.e. on D1) or OVX on estrus. There were no differences in plasma E2 and P levels in rats between estrus and early D1. However, after OVX on estrus, plasma levels of both steroids declined and were significantly lower 24 h later than values in D1 controls, indicating an active ovarian secretion of both hormones in this interval of the rat cycle. A significant increase in mean blood LH levels occurred between estrus and D1 due to an increase in LH pulse amplitude and frequency. After OVX on estrus, all parameters of pulsatile LH release also increased within 24 h, but mean blood LH levels as well as LH pulse amplitude and frequency were virtually identical to values in D1 controls, despite the decline in plasma E2 and P levels. Thus, OVX did not augment the increases in LH pulse amplitude and frequency that occur between estrus and D1. This demonstrates that the increase in pulsatile LH release from estrus to early D1 occurs in the absence of ovarian steroid negative feedback; the increases in LH pulse amplitude and frequency are not under negative feedback control by the low plasma levels of E2 and P present at this time. These data stand in direct contrast to the presence of prominent ovarian steroid negative feedback systems operative between D1 and diestrous day 2, and diestrous day 2 and proestrus. PMID- 4038647 TI - Biosynthesis of algal pheromones. A model study with the composite Senecio isatideus. AB - Several cyclic and alicyclic C11 hydrocarbons have been shown to act as gamete releasing and/or attracting pheromones during sexual reproduction of brown algae (Phaeophyceae). The same compounds are also found in the essential oils of various plants, of which the occurrence of the cycloheptadiene-pheromone ectocarpene in Senecio isatideus (Compositae) is noteworthy. Administration of [3H]dodeca-3,6,9-trienoic acid to cuttings of this plant leads to incorporation of radioactivity into ectocarpene. Double-bond-deuterated nona-3,6-dienoic acid is converted to fucoserratene, the pheromone of several Fucales, which is certainly not present among the hydrocarbons of Senecio. This proves that the pool of medium-chain, multiply unsaturated fatty acids includes precursors of all types of highly unsaturated hydrocarbons. Appropriately labelled (deuterium markers) fatty acid homologues were synthesized and applied to Senecio plantlets to unravel the mechanistic aspects. The results strongly suggest radical initiation of the pheromone biosynthesis by abstraction of a single hydrogen from a 1,4-pentadienyl segment of the fatty acid followed by oxidation to the corresponding cation. This causes fragmentation of the reactive intermediate into an olefine and carbon dioxide by neighbouring-group participation of the flanking double bonds. A tentative biosynthetic scheme is deduced from the experimental results which also sets the stereochemistry of the algal pheromones into a uniform mechanistic concept. PMID- 4038648 TI - Characterization and primary structures of DNA-binding HU-type proteins from Rhizobiaceae. AB - The DNA-binding HU-type proteins from several species of Rhizobiaceae including Rhizobium meliloti, two strains of Rhizobium leguminosarum with highly different phenotypic characters and Agrobacterium tumefaciens, were characterized and their amino acid sequences were determined. HU-type proteins isolated from R. leguminosarum L18 and A. tumefaciens are identical and show slight differences with the R. meliloti HU-type protein. On the other hand the R. leguminosarum L53 HU-type protein is quite different from the proteins cited above; several amino acid substitutions encountered in this protein result in significant changes in the folding of the polypeptide chain. The biochemical characteristics of these proteins are in good agreement with the respective position of these bacteria in the phylogeny determined by numerical taxonomy. PMID- 4038649 TI - Concurrent radiochemotherapy in the treatment of gynaecologic neoplasms. AB - Chemotherapy with adriamycin and/or cisplatinum in standard dosages concurrent with full radiation produced an accelerated local-regional tumour control leading to complete response in 12 of 14 patients who had advanced primary or recurrent gynaecologic neoplasms. The continuation of chemotherapy thereafter did not however prevent the development nor arrest progression of metastases outside the irradiated field. Epidermitis and myelosupression were the enhanced side effects but were tolerable and manageable. Radiochemotherapy can be applicable in situations where rapid shrinkage of the tumour bulk is required. Its other useful potentials deserve further evaluation. PMID- 4038650 TI - Polychemotherapy with carmustine, cyclophosphamide plus adriamycin in the treatment of advanced ovarian cancer. AB - The Authors describe their experience with a combination therapy with carmustine (BCNU), cyclophosphamide (CTX) plus adriamycin (ADM) in the treatment of advanced ovarian cancer. The complete remission was obtained in 33.3% of subjects, the partial remission in 37.5%. Almost all patients suffered nausea, vomiting and alopecia. Myelosuppression was acceptable. No heart damage was observed. This pharmacological association can be considered an effective medical treatment in the management of ovarian carcinomas in advanced stages. PMID- 4038651 TI - Breast metastasis of ovarian cancer during cis-platinum therapy. A case report and review of the literature. AB - Metastases of the breast are extremely rare. Organs with a high incidence of primary tumors are believed to be more highly resistant to secondary tumors. This paper reports on a case of right breast metastasis in a woman being treated for ovarian cancer with cis-Platinum therapy. Review of the literature and illustration of the nine cases so far reported. PMID- 4038652 TI - Tumor growth in liver atrophy and growth. An experimental study in rats. AB - Despite vast knowledge on liver regeneration, little is known about the effect of active liver atrophy and regeneration on tumor growth. Ligation of a branch of the portal vein to the one or two anterior lobes was performed in inbred Wistar rats. This induces acute atrophy of the anterior and regeneration of the other lobes. During the same operation a tumor cell suspension (NGW1--adenocarcinoma) was inoculated in liver lobes undergoing atrophy and regeneration. Tumor volume and weight were measured and the histologic appearance was assessed. During the early and active phases the tumor growth was significantly accelerated in regenerating lobes and partially inhibited in rapidly atrophied segments. After the regeneration and atrophy was completed the normal pattern of growth was re established in both parts of the liver. The results suggest that tumor growth is affected in proportion to regenerative response. They further suggest that portal branch ligation is of limited value in surgical palliation of liver tumors. The risk for further induction of growth of clinically undetected tumor foci in the remaining liver tissue appears to be small, although a significant, but short lasting, stimulatory response was found. PMID- 4038653 TI - Effect of AZQ (1,4-cyclohexadiene-1,4-diacarbamic acid-2,5-bis(1-aziridinyl)-3,6 dioxodiethylester) in recurring supratentorial malignant brain gliomas--a Phase II study. EORTC Brain Tumour Cooperative Group. PMID- 4038654 TI - Low-dose aminoglutethimide without steroid replacement in the treatment of postmenopausal women with advanced breast cancer. AB - Fifty-seven patients with actively progressing advanced breast cancer have been assessed for their response to low-dose aminoglutethimide (125 mg bd) without steroid replacement. Eleven women (19%) had an objective response while a further eight had stabilization of disease. However, one patient died with apparent adrenal insufficiency and another developed low plasma cortisol and serum sodium. Furthermore, 4/17 patients who had failed to respond to low-dose A/G subsequently responded when changed to conventional-dose A/G + steroid replacement, while three patients had stabilization of previously progressing disease. These results indicate that low-dose A/G without steroid replacement is potentially hazardous and that low-dose and conventional-dose A/G + steroids do not produce identical results. PMID- 4038656 TI - Chemotherapy of esophageal cancer. PMID- 4038655 TI - Relationship between leukemic cell retention of cytosine arabinoside triphosphate and the duration of remission in patients with acute non-lymphocytic leukemia. AB - Bone marrow cells were obtained from patients with acute non-lymphocytic leukemia immediately prior to the administration of cytosine arabinoside/anthracycline antibiotic remission induction therapy. The ability of the leukemic cells to take up and phosphorylate cytosine arabinoside (araC) and to retain cytosine arabinoside triphosphate (araCTP) was measured and compared to the outcome of remission induction therapy and the duration of remission. While the outcome of remission induction therapy was unrelated to cellular metabolism of araC, the duration of remission was highly correlated with araCTP retention. A comparison of the remission durations of patients treated on successive chemotherapeutic protocols suggests that the benefits of intensive remission consolidation therapy may be limited to patients whose leukemic cell retention of araCTP is low and that aggressive consolidation chemotherapy may reduce the prognostic significance of araCTP retention. PMID- 4038657 TI - Cell proliferation kinetics in the gastric remnant. AB - Biopsy specimens of the gastroenterostomal area in 60 long-standing asymptomatic postgastrectomy patients and of the mid-corpus region in five normal controls were cultured in [3H]-TdR. Using radioautography, thymidine incorporation rate (TIR) and cell position of the labelled cells were scored. In the normal gastric mucosa cell proliferation was limited to the progenitor cell region. TIR of the stomal area was higher compared to the normal mucosa. In addition, an upward shift of the proliferative compartment towards the luminal surface was observed. In severe dysplasia an expanded pool of DNA-synthesizing cells was present in the uppermost layers of the gastric mucosa, but even in the surrounding non dysplastic mucosa an upward shift of labelled cells could be demonstrated. These proliferative changes are considered to be compatible with increased cancer risk. The sequence of proliferative events suggests that early cancer formation in the gastric remnant takes place in the superficial mucosa and therefore is easily amenable to endoscopic biopsy. PMID- 4038658 TI - Evaluation of luteal-phase salivary progesterone levels in women with benign breast disease or primary breast cancer. AB - Salivary progesterone concentrations were determined in premenopausal parous women with a mean age of ca. 40 yr who had a history of either benign breast disease (n = 15) or primary breast cancer (n = 15) and in a group of age-matched healthy women (n = 15). Saliva samples were collected at 09.00 and 21.00 hr daily for one complete menstrual cycle and progesterone concentration was measured by radioimmunoassay. Characteristic luteal-phase progesterone profiles were observed in all subjects in each of the three groups but no statistical intergroup differences could be demonstrated for age-matched subjects in each group. These studies indicated that ovarian dysfunction, as judged from salivary progesterone concentrations, was not apparent in older premenopausal women with a history of benign breast disease or primary breast cancer when compared with age-matched controls. PMID- 4038659 TI - Isolation of microvillar microfilaments and associated transmembrane complex from ascites tumor cell microvilli. AB - The association of microvillar microfilaments with the microvillar membrane actin containing transmembrane complex of MAT-C1 13762 ascites tumor cell microvilli has been investigated by differential centrifugation, gel electrophoresis and electron microscopy of detergent extracts of the isolated microvilli. Several methods have been used to reduce breakdown and solubilization of the microfilament core actin during the detergent extractions for preparation of microvillar core microfilaments. Gel electrophoresis of differential centrifugation fractions demonstrated that over 70% of the total microvillus actin could be pelleted with microfilament cores at 10 000 g under extraction conditions which reduce filament breakdown. Transmission electron microscopy (TEM) of all of the core preparations showed arrays of microfilaments and small microfilament bundles. The major protein components of the microfilament cores, observed by sodium dodecyl sulfate (SDS) electrophoresis, were actin and alpha actinin. Among the less prominent polypeptide components was a 58 000 Dalton polypeptide (58 K), previously identified as a member of the MAT-Cl transmembrane complex. This three-component complex contains, in addition to 58 K, actin associated directly and stably with a cell surface glycoprotein (Carraway, CAC, Jung, G & Carraway, K L, Proc. natl acad. sci. US 80 (1983) 430). Evidence that the apparent association of complex with the microfilament core was not due simply to co-sedimentation was provided by myosin affinity precipitation. These results provide further evidence that the transmembrane complex is a site for the interaction of microfilaments with the microvillar plasma membrane. PMID- 4038660 TI - Translation of messenger RNA from a renal tumor into a product with the biological properties of erythropoietin. AB - The renal tumor RCC-3-JCK, when transplanted into immunodeficient mice, caused an erythrocytic polycythemia. When grown in culture, the tumor cells secreted a substance into the culture medium that chromatographed by size-exclusion high performance liquid chromatography similarly to purified human erythropoietin (Ep) and was positive when assayed for Ep by its ability to stimulate erythropoiesis in fetal mouse liver cells (the FMLC assay). The poly(A) + RNA was extracted from the tumor cells and injected into Xenopus oocytes, inducing the appearance of Ep(FMLC) in the oocyte culture medium. Both the tumor cells and oocyte culture media were fractionated by size-exclusion high-performance liquid chromatography, and two fractions with Ep(FMLC) activity were found in the tumor-cell culture medium. Three active fractions were found in the medium from the mRNA-injected oocytes. The largest component from both culture media had the same elution time as a human standard (Ep). The poly(A) + RNA was fractionated by sucrose density gradient centrifugation and the 8S and 10S fractions were found to induce Ep(FMLC) synthesis when they were injected into the oocytes. We conclude that poly(A) + RNA isolated from the Ep-producing tumor RCC-3-JCK included mRNA for Ep and that the Ep was a translational product of Xenopus oocytes injected with this mRNA. PMID- 4038662 TI - Circling behavior in mice and rats: possible relationship to isolation-induced aggression. AB - The relationship between circling behavior (rotation), isolation, and aggression was investigated in normal male mice and rats. Initially the animals were tested for spontaneous nocturnal rotation, then conspecific aggression and muricidal behavior was observed for mice and rats respectively. Subsequently, animals were paired on the basis of net nocturnal rotations and either group-housed or individually housed. Four weeks later all animals were retested for the same behaviors. Spontaneous nocturnal rotation increased significantly for the isolated mice but not for the group-housed animals. Moreover, 9 of the 10 isolates became aggressive and their net rotations were significantly and positively correlated with the number of biting attacks. None of the group-housed mice became aggressive. Rats, on other hand, showed a decrease in rotation and a relationship between rotation and muricidal behavior was not evident. The possible relationship between circling behavior, aggression, and territoriality is discussed. PMID- 4038661 TI - Role of the cat substantia nigra pars reticulata in eye and head movements. I. Neural activity. AB - Single unit activity was recorded in the Substantia Nigra pars reticulata (SNpr) of cats trained to orient their gaze toward visual and/or auditory targets. Cells in the SNpr have a steady high rate of spontaneous activity ranging from 35 to 120 spikes per second. The neurons respond to sensory stimuli or in relation to saccadic eye movements with a decrease or a cut-off of the spontaneous discharge. Among 109 cells recorded in the SNPR 60 were responsive to visual stimuli (mean latency = 118 ms). Most of the receptive fields which were plotted were large encompassing part of the ipsilateral field. Thirty nine (39) cells were responsive to auditory stimuli (mean latency = 81 ms). A majority of these cells showed a better response for stimuli located in the contralateral hemifield. In a few cells, the sensory responses were modulated by the subsequent orienting behavior of the animals. Thirty one (31) cells showed a response in relation to saccades. These units typically stopped discharging between 50 and 300 ms prior to the onset of the saccade. 39% of these units also responded in relation to spontaneous saccades in the dark. 61% of the saccadic cells also responded to sensory stimuli in the absence of saccades. Six (6) cells were found to respond to active head movements. These results are discussed in the framework of the role that the basal ganglia might have in the selection of the sensory stimuli that trigger orienting behaviors. PMID- 4038663 TI - Morphology of the intercapsular segment of the oviduct in the golden hamster with special reference to ovum-transit from ruptured follicles to the ampulla. AB - The intercapsular segment of the oviduct in the golden hamster is not a simple duct which has constant outer and inner diameters. After penetrating the bursa ovarica the ICS has a circular constriction and the corresponding oviductal lumen is narrowed. PMID- 4038664 TI - Colchicine-induced appearance (proliferation) of smooth sarcoplasmic reticulum in arterial smooth muscle cells. AB - Colchicine treatment resulted in the appearance and proliferation of smooth sarcoplasmic reticulum in some smooth muscle cells of the aortic and pulmonary trunk walls in the rabbit. The significance of cytoplasmic microtubules and/or membrane-bound tubulin for the morphogenesis, functioning and control of smooth endoplasmic reticulum in different kinds of cells is discussed. PMID- 4038665 TI - Purification and characterization of the gonad lectin of Aplysia depilans. AB - Extracts of gonads and fertilized eggs of Aplysia depilans contain a D galacturonic and D-galactose-binding lectin. This lectin reacts strongly with rabbit and human erythrocytes independent of ABO blood groups, weakly with dog, mouse, rat, and chick erythrocytes and not at all or very weakly with sheep erythrocytes. Purification of the gonad lectin was easily achieved, with a high yield, by heating to 70 degrees C, precipitation with ammonium sulfate and affinity chromatography on Sepharose 4B. The purified lectin was found to be a glucoprotein of molecular mass around 55-60 kDa; it stimulates mitogenesis of human peripheral lymphocytes. PMID- 4038666 TI - [Energy support and the contractile capacity of glycerinized myocardial fibers in experimental informational neurosis]. AB - Experiments in dogs revealed that in informational neurosis the ability of myocardial contractile protein system (myocardial glycerinized filament bundles) to develop tension and produce work as well as the power of the contractile process are considerably reduced. Obviously, the energy production is not disturbed as a lower myocardial content of ATP (by 12%) and particularly of CP (by 54%) is caused by 8-9-month hypokinesia. Analogous shifts seem to occur in the human heart in informational neurosis which, in combination with the reduced intensity of the calcium transport by sarcoplasmic reticulum and mitochondria, may underlie the development of heart weakness. PMID- 4038667 TI - Development of cortical polarity in mouse eggs: involvement of the meiotic apparatus. AB - Experiments were carried out to determine the origin of cortical polarity in mouse eggs and its possible relation to the meiotic apparatus. Cortices of mature eggs overlying the meiotic apparatus (microvillus-free area) were distinguished by an absence of microvilli and a thickened layer of actin. In contrast, the surfaces of immature oocytes were covered entirely with a dense population of microvilli and were subtended by a uniform layer of actin. When induced to undergo maturation, meiotic spindles formed in the center of immature oocytes and then moved peripherally. Coincident with the cortical localization of the meiotic spindle was the formation of a microvillus-free area, i.e., a loss of microvilli and a thickening of the actin layer associated with this region of the egg cortex. If immature oocytes were incubated in cytochalasin B, meiotic spindles formed; however, they failed to move peripherally and microvillus-free areas did not develop. Oocytes incubated in colchicine did not form meiotic spindles, although the chromosomes condensed and became localized to cortices where microvillus-free areas developed. Cytochalasin B-treated mature eggs maintained intact meiotic spindles and exhibited a disappearance of microvillus-free areas and a reduction in cortical actin. The chromosomes of mature eggs treated with colchicine remained associated with microvillus-free areas despite the disappearance of meiotic spindles. Occasionally, colchicine-treated eggs possessed more than one cortically located mass of chromosomes, each of which was associated with a microvillus-free area. These observations indicate that mechanisms involving the movement of the meiotic spindle to the oocyte cortex and development and maintenance of cortical polarity are cytochalasin B sensitive. Commensurate with the localization of meiotic chromosomes to the egg cortex is the reorganization of cortical actin and the formation of a microvillus-free area. PMID- 4038668 TI - Altered trophoblast functions in implantation-defective mouse embryos. AB - Extracellular proteases, such as plasminogen activator (PA), may play a role in the invasive action of trophoblasts during blastocyst implantation in mice. Detailed analysis of proteases released by trophoblasts must be carried out in culture for practical reasons, but the in vitro results should ideally be related to implantation in utero to test the validity of the conclusions in the model system. The implantation-defective mutant (tw73) allows us to investigate alterations of trophoblasts in culture which will reflect their altered functions in utero. The trophoblasts of mutant embryos attached and proliferated in culture to the same extent as control embryos. Therefore, the mutant effect is not to kill or stop the division of these cells. However, trophoblasts of tw73 homozygotes showed decreased invasive ability when transplanted into testes. To examine the biochemical basis of altered invasive behavior in mutants, PA activity released by blastocysts in culture was measured. Medium conditioned by tw73 homozygotes contained less PA fibrinolytic activity than culture medium of control embryos. The correlation between decreased in vitro PA activity and the invasive defects seen in utero and ectopically, supports the involvement of PA in the invasive phase of the implantation process. PMID- 4038669 TI - The minimally hearing-impaired child. AB - This paper reviews evidence which suggests that middle ear disease with effusion and associated hearing loss, unilateral sensorineural hearing impairment, and mild bilateral sensorinural hearing loss in children can result in far more educational and/or communicative difficulty than was previously supposed. The author rejects the notion that a decibel level on an audiogram truly reflects the degree of hardship the child experiences and argues for a more active identification and management program in the early years. PMID- 4038670 TI - [Use of specific DNA probes for mapping the ceruloplasmin gene on rat chromosomes by direct in situ hybridization]. AB - Specific DNA-probes representing the fragments of chromosomal ceruplasmin gene (lambda RCp-1, lambda RCp-2, lambda RCp-3) and its cDNA copy of the corresponding mRNA were heavily labelled with 125J dCTP (the specific activity of the probes varying from 1.5 X 10(7) to 3.4 X 10(8) dpm). These probes were used for in situ hybridization on metaphase chromosomes. The total number of silver grains and their distribution along differentially stained chromosomes were determined in 653 metaphase plates from bone marrow cells of laboratory rats. The results of in situ hybridization were very similar for all four specific DNA-probes tested and allow to assign ceruplasmin gene to the q13 region of chromosome 7. The local increase of silver grain count over chromosome 15 was also registered and discussed. PMID- 4038671 TI - [Statistical analysis and experiment planning in the test for the induction of anomalous sperm in mice]. AB - The work deals with analysis and planning of experiments in one of the testing methods for potential genetic activity of chemicals--in the test for sperm abnormality in mice. A novel way of analysis of experimental data using consecutive scheme of microscopy of preparations has been suggested which came to be more convenient and economically advantageous in routine work. PMID- 4038672 TI - The effect and mode of action of zinc pyrithione on cell growth. II. In vivo studies. AB - The effect of topical application of the anti-dandruff agent zinc pyrithione (ZnPTO) on epidermal DNA synthesis in normal and hexadecane-stimulated rat skin was investigated. Autoradiography was used to determine the percentage of epidermal cells labelled with [3H]thymidine (labelling index). ZnPTO at 1% in shampoo base caused a slight increase in the labelling index in normal skin, similar to the effect of the shampoo base alone. No effect of 1% ZnPTO as an aqueous dispersion was observed. ZnPTO at 1% in shampoo base did not reduce the large increase in labelling index produced by hexadecane, nor did shampoo base alone or 1% ZnPTO in water. The shampoo base with or without 1% ZnPTO had only a very slight effect on the histopathology of normal and hexadecane-treated skin, and 1% ZnPTO in water had no effect. It is concluded that the in vitro potential of ZnPTO to cause growth inhibition is not achieved in vivo, presumably because of low percutaneous absorption. This evidence does not support a cytostatic mode of action in clearing dandruff. PMID- 4038673 TI - Genetic toxicology in the food industry. AB - In vitro testing of food products for mutagenic activity presents particular problems, especially in connection with the administration of the test material to the assay system, the possible interference of food components with the genetic end-point used for the assay, the presence in foods of various factors that may modify mutagenic activity, the identification of appropriate negative or positive controls and the avoidance of artefactual mutagen formation during the preparation of test samples. Ideally mutagenicity testing requires in vivo studies (although these too have particular problems when applied to foods) but, at present, in vitro tests provide the only practical means of screening large numbers of food samples or modifying factors and of assessing food-processing techniques. The tests can be carried out on model systems (e.g. amino acid/sugar mixtures), on isolated and purified constituents of foods, on fractionated solvent extracts or on whole-food homogenates subjected to digestion procedures. However, to determine genotoxic risk from foodstuffs, quantitative data from mammalian in vivo tests and from human consumption and metabolism studies are also required. PMID- 4038674 TI - Comparison of percutaneous absorption of fragrances by humans and monkeys. AB - The percutaneous absorption of two cosmetic fragrance materials, safrole and cinnamyl anthranilate, as well as of cinnamic alcohol and cinnamic acid, has been measured at occluded and non-occluded application sites. Absorption values were determined in the rhesus monkey in vivo. Absorption through human skin was measured by using excised skin in diffusion cells. Because of the insolubility in water of safrole and cinnamyl anthranilate, a nonionic surfactant solution (6% oleth 20) was used in the receptor chamber of the diffusion cell in order to facilitate the partitioning of the compounds from the skin into the receptor fluid. The relative volatility of the compounds was determined in order to aid in the interpretation of the absorption results. The greatest difference between in vivo and in vitro absorption values occurred with safrole, which was the least well absorbed and the most volatile compound. Cinnamic acid absorption through non-occluded human skin (17.8 +/- 4.9%, mean +/- SEM) was significantly lower than through monkey skin (38.6 +/- 8.3%). The values for absorption through human and monkey skin did not differ significantly for cinnamyl anthranilate (24.0 +/- 5.1% v. 26.1 +/- 2.3%) or cinnamic alcohol (33.9 +/- 7.3% v. 25.4 +/- 4.4%). Occlusion of the skin resulted in greater permeation of all of the compounds; a significant difference in permeability between the two types of skin occurred only with safrole. The fragrances were absorbed well, but their volatility must be considered in a toxicity evaluation. There was reasonable agreement between the values obtained from the studies of the human skin in vitro and the monkey skin in vivo. PMID- 4038675 TI - Suitability of the P388F mouse lymphoma system for detecting potential carcinogens and mutagens. AB - The P388F mouse lymphoma (TK +/-) system has been evaluated further for use as a primary mammalian-cell test and as a complementary assay to the Ames Salmonella reverse-mutation assay. The system showed a clear dose response with three alkylating agents of previously demonstrated genotoxic potential and gave the anticipated positive result with benzo[a]pyrene in the presence of S-9 mix. In addition, while giving the expected negative result with sugar, the assay detected genotoxic activity in hexamethylphosphoramide, acrylonitrile and formaldehyde, all of which are known to give negative results in the Ames test. PMID- 4038676 TI - Aflatoxin exposure and human liver-cancer risk. PMID- 4038677 TI - The effect of L-histidine on acute cobalt intoxication in rats. PMID- 4038678 TI - Genetic toxicology in the pharmaceutical industry. AB - The main objective of the pharmaceutical industry is health protection. Drugs not intended for use in life-threatening diseases should be free from toxic effects, but every natural or man-made chemical has potential toxicity depending on the exposure dose. The pharmaceutical industry considers genetic toxicology as a part of overall safety evaluation. No single genetic toxicity test is satisfactory; a battery of test is necessary to cover the whole spectrum of genetic events. Numerous tier approaches have been proposed for mutagenicity testing but from the toxicological viewpoint a phylogenic testing model seems more appropriate than a sequential step model. Evaluation of the mutagenic potential of drugs should rely on in vivo animal models, although for screening purposes and to promote understanding of the mutagenic action, in vitro tests using different systems can be used. Rejection solely on the basis of in vitro tests can lead to the unnecessary loss of a valuable drug. More inexpensive and relatively short tests on non-mammalian and mammalian cells are needed for studying structure-mutagenic activity relationships. For extrapolating to man and in the framework of clinical studies, it might be worthwhile to focus more time on developing inexpensive and simple tests using models directly relevant to man (e.g. human body fluids). PMID- 4038679 TI - Biomonitoring of exposure to potential mutagens and carcinogens in industrial populations. AB - Methods for monitoring exposure to potential industrial mutagens and carcinogens fall into two distinct groups. The tests in the first group measure the concentration of the substance, of its metabolites or of the products of its reaction with cellular macromolecules, in biological media. Such tests include the determination of urinary metabolites of the chemical, the measurement of nucleic-acid or protein adducts and the determination of urinary thioethers. The second group comprises assays of biological endpoints that may be the result of the organism's reaction to exposure. These endpoints include chromosomal aberrations in peripheral lymphocytes and sister chromatid exchanges. Each test has advantages and limitations that will affect its suitability for use in specific industrial situations. PMID- 4038681 TI - Inhibition by plant phenols of benzo[a]pyrene-induced nuclear aberrations in mammalian intestinal cells: a rapid in vivo assessment method. AB - The polycyclic aromatic hydrocarbon, benzo[a]pyrene, induced dose-related nuclear damage (micronuclei, pyknotic nuclei and karyorrhectic bodies) in colonic epithelial cells of C57BL/6J mice within 24 hr when administered intrarectally in single doses of 0-200 mg/kg body weight. This damage was reduced when mice ingested the plant phenols, caffeic, ferulic and ellagic acids, and quercetin at levels of 4% or BHA at 2% (w/w) in the diet for 1 wk prior to the benzo[a]pyrene challenge (100 mg/kg body weight). Benzo[a]pyrene-induced nuclear damage was not significantly inhibited by 4% curcumin under similar conditions. The inhibition of nuclear damage is consistent with reported antimutagenic effects for these agents in vitro and in longer term animal studies. The procedure described here may provide a rapid in vivo method for assessing the potential of natural products to inhibit the carcinogenic process. PMID- 4038680 TI - The role of mutagenicity testing in the ecotoxicological evaluation of industrial discharges into the aquatic environment. AB - An important task of ecotoxicology is to provide data for use by governments as a scientific basis for regulating the discharge of potentially hazardous substances into the environment. The criteria on which such regulations are based include biological and chemical degradability, bioavailability (accumulation) and toxicity, the latter manifesting itself in a reduced ability of organisms to survive and reproduce. There are also arguments for including the mutagenicity of chemicals in these criteria. In the past decade many studies have revealed the contamination of water and the atmosphere by mutagens originating in human activities and having observable effects on organisms in these environments. The extent to which this mutagenic stress can alter ecosystems as a whole is not yet known, but if mutagens are shown to cause major changes, mutagenicity is clearly an important ecotoxicological criterion. In the meantime its use must be based on the actual damage caused to organisms by mutagens and on the rising concern over a novel ecological phenomenon that might be named 'increased mutagenic stress'. A detailed report on the ecotoxicological case history of the discharge from a nitrofuran factory demonstrates the role of mutagenicity tests in the evaluation of effluents. As well as being toxic to algae, the discharge was found to be mutagenic in the Ames test. Toxicity and mutagenicity were used as criteria in studies of the biodegradability of the offending substances in a chemostat, as well as in studies to monitor the success of detoxification attempts. In the chemostat the mutagens did not appear to be very degradable but the algal toxicity decreased by 90%. Detoxification was reasonably successful for the mutagens in contrast to the algal toxicants. PMID- 4038682 TI - Genetic toxicology in industrial practice: general introduction. AB - During the past decade, important position statements on mutagenicity testing have been issued by industrial organizations such as CEFIC (the European Council of Chemical Industry Federations) and ECETOC (the European Chemical Industry Ecology and Toxicology Centre). Mutagenicity testing is of potential value as a research tool for screening new compounds, as a probe for the identification of harmful substances and as a diagnostic tool for monitoring the health of individuals exposed to certain chemicals. The problems inherent in mutagenicity testing include specificity and sensitivity, and meaningful interpretation of test data will depend on the strict maintenance of accepted quality standards. PMID- 4038683 TI - Comparative pharmacokinetics of vitamin A (retinol) in rats and hamsters. AB - The absorption and elimination of all-trans-retinol in the plasma of rats and hamsters were studied after an oral dose of 45 mg/kg body weight. The hamsters exhibited a higher pretreatment mean circulating retinol concentration than rats maintained on an identical diet. The increase in plasma retinol after a single oral dose was much greater in hamsters than rats. The area under the plasma concentration v. time curve was approximately 60% greater for rats than for hamsters. The elimination half-times for rats were much longer than for hamsters. Plasma retinol uptake and disappearance were consistent with a two-compartment open model with first-order absorption. PMID- 4038684 TI - Effect of serum-parathion interactions on cutaneous penetration of parathion in vitro. AB - The effect of serum and serum fractions on the cutaneous penetration of [35S]parathion from surface deposits or adsorbed formulations was determined. The total quantity of [35S]parathion which penetrated pig skin was significantly greater when the receptor fluid was whole swine serum or the 500 or 10,000 MW retentate from ultrafiltration of the serum than when phosphate-buffered saline (PBSA), the 500 MW filtrate or distilled water, respectively, was used. The enhanced penetration was observed without any associated evidence of metabolic change and with both dosing methods. This result is consistent with the hypothesis that serum-parathion interactions are the cause of the enhanced penetration. The apparent solubility of parathion was 16 times greater in whole serum than in PBSA. Gel-filtration chromatography of the serum-parathion mixture revealed that approximately 11% of the 35S activity was associated with two protein fractions which had consistently different elution volumes. Most of the radioactivity, however, was not tightly bound and the equilibrium between bound and free parathion was rapidly reversible. The result of interaction between parathion and serum proteins was an increased apparent solubility, relative to PBSA, and increased cutaneous penetration. The significance of these findings is clear: when designing in vitro systems to model in vivo percutaneous absorption, investigators should consider that the affinity of the fluid interfacing with the dermis in vivo may influence the kinetics of penetration when subcutaneous blood flow is low. PMID- 4038685 TI - Influence of age and environment on the induction of mammary tumours by diethylstilboestrol in C3H/HeN-MTV+ mice. AB - C3H/HeN-MTV+ female mice were fed diets containing targeted concentrations of 320 or 640 ppb diethylstilboestrol (DES) starting at 3, 5, 7 or 11 wk of age and continuing throughout their remaining lifespan. Mice were housed in either a single-corridor conventional animal room or in a double-corridor barrier-type animal room. Mice housed in the conventional animal room and started on DES at 7 or 11 week of age developed palpable mammary tumours somewhat sooner than the corresponding groups of mice kept in the barrier animal room. In mice housed in the barrier animal room and exposed to a given DES concentration, there was very little difference between mice started on DES at 3, 5 or 7 wk of age in the exposure time required for the development of palpable mammary tumours. There was a striking difference, however, between mice started on DES at 7 wk and those started at 11 wk of age in the exposure time needed before mammary tumours appeared. Mice started at 11 wk of age developed tumours with, on average, about 4 wk less exposure than did those started at 7 wk. This suggests that treatment between 7 and 11 wk of age had little or no effect on mammary tumour development. In conclusion, both animal-room environment and age at the start of DES treatment influenced the mammary tumour response in female C3H/HeN-MTV+ mice. PMID- 4038686 TI - A carcinogenicity study with mutagenic organic concentrates of drinking-water in the Netherlands. AB - The carcinogenicity in male and female Wistar SSP TOX rats of organic drinking water concentrates that are positive in the Ames test was studied at three doses. The organic mutagenic concentrates were prepared weekly from drinking-water from one location in The Netherlands by adsorption onto XAD-4/8 resins and elution with dimethylsulphoxide. The organic concentrates in dimethylsulphoxide were mixed with non-mutagenic drinking-water before exposure of the rats. Dose levels were based on multiples of expected human exposure levels. For the calculation the average human daily intake of drinking-water was taken as 2 litres for a body weight of 70 kg. There was no significant increase in tumour induction when male Wistar SSP TOX rats were exposed for 106 wk to 4.5, 14 or 40 times the expected human exposure level and females to 7,22 or 68 times the human level. The development and types of tumours were similar in the treated and control groups. The numbers of animals with tumours and of animals that died as a result of tumours in the exposed groups did not differ significantly from those in the control groups. These results suggest that these organic mutagenic drinking-water concentrates did not contain very potent carcinogens in effective concentrations. PMID- 4038688 TI - Preop education can cut LOS and cost, aid PPS delivery. PMID- 4038687 TI - Sensory irritation potential of selected nasal tumorigens in the rat. AB - Several important chemicals, including formaldehyde, 1,4-dichloro-2-butene, bis chloromethyl ether, hexamethylphosphoramide, and epichlorohydrin have been shown to produce nasal tumours in rats following repeated or continuous inhalation exposures. Some of these compounds are respiratory irritants. To determine whether there is a correlation between the ability of a chemical to produce sensory irritation and to elicit nasal tumours, the atmospheric concentration causing a 50% decrease in the respiratory rate (RD50) of male rats was determined. Three other nasal tumorigens, dimethylcarbamoyl chloride, 2,3,4 trichloro-1-butene and 1,2-ethoxy-3-phenoxypropane, were also studied. No correlation between sensory irritation potency and nasal tumorigenic potential was observed. The most potent nasal tumorigen hexamethylphosphoramide, which produces tumours in rats following 12 months' continuous exposure to 50 ppb, failed to cause any decrease in respiratory rate when tested at 351 ppm (an aerosol exposure level which exceeds atmospheric saturation by approximately ten times). PMID- 4038689 TI - Social workers highlight roles under PPS. PMID- 4038691 TI - Genetic heterogeneity of hypertrophic cardiomyopathy. AB - We studied the pattern of inheritance of hypertrophic cardiomyopathy among 111 first-degree relatives of 30 patients with the disease. Results of segregation analysis suggest a genetic heterogeneity for hypertrophic cardiomyopathy in that both autosomal dominant and autosomal recessive mode of inheritance can occur. PMID- 4038690 TI - Gc serum groups in schizophrenia. AB - Gc subtypes were studied by isoelectric focusing in schizophrenic patients and controls. No significant differences between patients and controls were found. The results so far on Gc groups and schizophrenia show no consistent pattern and the significant associations reported have not been confirmed. PMID- 4038692 TI - Time of onset of chest pain in acute myocardial infarction. AB - We studied the time of onset of chest pain in 1099 patients admitted to a coronary care unit with myocardial infarction using a statistical model. Statistical analysis demonstrated an excess of infarcts with time of onset of chest pain at 0700 hours (14%) and at midnight (11%), with the remaining infarct population (75%) forming a background distribution over the 24 hr. PMID- 4038693 TI - Use of nifedipine in hypertrophic cardiomyopathy in infants. A report of two cases. PMID- 4038694 TI - Study of central regulation of intraocular pressure using ventriculocisternal perfusion. AB - The ability of hypoosmotic solution, prostaglandin E1 (PGE1) and clonidine to influence intraocular pressure (IOP) by a central mechanism was studied using the technique of ventriculocisternal perfusion in conscious rabbits. IOP remained unchanged during the perfusion of 150 mOsm artificial cerebrospinal fluid. IOP rapidly increased by 15 mmHg during the perfusion of PGE1 at the dose of 1 or 3 micrograms/min. However, when PGE1 was perfused intravenously at the dose of 1 microgram/min, a similar IOP response was observed. Furthermore, during the ventriculocisternal perfusion of PGE1 a significant systemic absorption occurred. These observations indicate that the ocular hypertension during the ventriculocisternal perfusion of PGE1 is primarily due to the peripheral action of systematically absorbed PGE1. IOP gradually decreased by 3 mmHg during the ventriculocisternal perfusion of clonidine at the dose of 0.1 or 0.33 micrograms/min. Intravenous perfusion of clonidine at the same doses did not change the IOP. These results indicate that clonidine can lower IOP by a centrally mediated mechanism. Ventriculocisternal perfusion of clonidine (0.1 micrograms/min) in rabbits with unilateral superior cervical ganglionectomy lowered IOP in both eyes, indicating that ocular adrenergic innervation does not participate in this centrally mediated IOP response. However, the cardiovascular parameters of anesthetized rabbits were altered by the ventriculocisternal perfusion of clonidine (0.1 micrograms/min), suggesting that a change in systemic hemodynamics is involved in the central IOP effect of clonidine. PMID- 4038695 TI - Acute effects of dexamethasone on intraocular pressure in glaucoma. AB - The effects of 3 mg orally administered dexamethasone on the intraocular pressure (IOP) were examined in four patients with primary open-angle glaucoma hospitalized for this study. Plasma-free glucocorticoid activity was measured by a radioreceptor assay. Diurnal rhythms of IOP and plasma-free glucocorticoid activity were detected prior to administration of dexamethasone. The plasma-free glucocorticoid activity rose two- to threefold in the 30-min period following steroid administration and then declined throughout the rest of the day. IOP was approximately 2 mmHg higher in the 0-4-hr period and approximately 5.5 mmHg higher in the 4-8-hr period following the pharmacologic doses of dexamethasone compared with similar periods on control days. The increase in the IOP was highly significant (P less than 0.006) in the latter time period. These findings suggest that the glucocorticoids may have a greater role in regulating IOP than generally has been appreciated. PMID- 4038696 TI - Some functional characteristics of purified bovine interphotoreceptor retinol binding protein. AB - Interphotoreceptor retinol-binding protein (IRBP) is a unique retinol carrier: it is a large glycoprotein existing only in the interphotoreceptor matrix (IPM), which is the extracellular material situated between and behind the photoreceptors of the neural retina. IRBP from bovine and human eyes carries endogenous retinol, as evidenced by the protein's fluorescence on gel-filtration (Sephacryl S-300) chromatography and on native (non-SDS) pore-gradient polyacrylamide gel electrophoresis. Bovine IRBP's retinol-binding sites are at most one-third occupied in light-adapted eyes and much less in dark-adapted eyes; this bleach dependence is partially reversible and suggests a role in vitamin A transport during the visual cycle. IRBP can be saturated with exogenous all-trans retinol; one ligand molecule binds per protein molecule. IRBP can be isolated rapidly from IPM by affinity adsorption onto con A-Sepharose; this preparation is 94% pure and yields 0.33 mg or 2.4 nmol of IRBP per bovine eye. An apparently homogeneous preparation can be obtained by subsequent passage through a Sepharose 4B column. IRBP is located only in the IPM, which is harvested by isotonic washing of the retina. (In the absence of this rinse to prepare IPM, the protein is found loosely associated with the retina, although not as a cellular or membrane component.) As the thoroughness of the retinal washing procedure is increased, the yield of IPM proteins (including IRBP) goes up; however, the same set of proteins, in the same ratios, always is retrieved, indicating that retinal cell components do not contaminate seriously the IPM. PMID- 4038697 TI - Assessing the financial characteristics of multi-institutional organizations. AB - The prospective pricing of health services is precipitating greater attention to financial characteristics and greater development of multi-institutional organizations (MIOs). This study compares the financial characteristics of 1,590 MIO hospitals with 2,819 freestanding hospitals by ownership type: church operated, other not-for-profit, and investor-owned. Using 1981 data from the American Hospital Association, the hospitals' capital structure and profitability are measured using three financial ratios: total assets-to-equity, return on equity, and operating margin. The results indicate both greater leverage and greater profitability among MIO hospitals, particularly in the investor-owned sector. The implications of these findings are discussed relative to financial performance by hospital ownership type in the future. PMID- 4038698 TI - Effect of prepubertal versus postpubertal castration on sexual and aggressive behavior in male horses. AB - Males horses castrated prepubertally occasionally display stallion-like sexual and aggressive behavior as adults. A retrospective survey of 140 horse owners was undertaken to compare the effectiveness of prepubertal versus postpubertal castration on objectionable sexual and aggressive behavior. Of 94 geldings that had been castrated prepubertally (before 2 years of age), 20% to 30% displayed stallion-like sexual behavior and aggression toward horses, and 5% were aggressive toward people in a stallion-like manner. This occurrence of problem behavior was not significantly different from the occurrence of these behavioral patterns in 46 geldings that had been castrated as stallions (over 3 years of age). When castration was examined as a therapeutic measure to eliminate sexual and aggressive behavior in stallions in which the behavior had become objectionable, it was found that the operation was effective on sexual behavior and aggression toward people in 60% to 70% of horses and on aggression toward horses in 40% of horses. PMID- 4038699 TI - Vaginal evisceration of the small intestine in three mares. AB - Three mares were treated for vaginal evisceration of a portion of the small intestine. Evisceration occurred in 2 mares shortly after breeding accidents in which the stallion's penis penetrated the vaginal fornix dorsal to the cervix. The affected bowel was replaced through the laceration, and the vaginal defects were sutured with the mares standing, utilizing epidural anesthesia. One mare recovered without complications, was subsequently bred, and delivered a foal with no difficulty. The other mare developed signs of a strangulating small intestinal obstruction 24 hours after the injury, necessitating exploratory celiotomy. Two meters of small intestine had become devitalized secondary to avulsion of the mesentery and adjacent vascular supply during the evisceration. The affected portion was resected and a jejunocecostomy was performed. Recovery was uncomplicated and 21 months later the mare was 9 months in foal. A third mare was treated unsuccessfully for evisceration of several meters of small intestine through the external urethral orifice after rupture of the urinary bladder. PMID- 4038701 TI - Behavior and performance of weanling pigs in pens equipped with hide areas. AB - Two-hundred eighty crossbred pigs were used to determine the efficacy of hide areas (hides) in reducing young pigs' aggressive activity during social stress and the effect of access to hides on young pigs' productive performance. In Exp. 1, 80 pigs were kept in littermate groups of five/pen in 16 home pens. Then one pig was randomly selected from each of four pens, and the four were regrouped in either a control pen or a pen equipped with three hides (each a 20 X 23 X 25 cm box) in one of the walls. Behavior was time-lapse video-recorded for 90 min. Time spent either eating (head-in-feeder) or lying was not affected by access to hides. Pigs with hides to use in escaping attack fought less during the initial 30 min after regrouping. They spent an average of 5.5% of the time with heads hidden during the entire 90-min observation period. Experiment 2 employed 200 pigs in a performance study designed to evaluate effects of regrouping and access to hides on body weight gain and feed conversion efficiency. There were 10 replicates of each of four treatments: (a) regrouped-control pen, (b) regrouped hide pen, (c) littermates-control pen and (d) littermates-hide pen. During the first 7 d of the 21-d trial, treatments tended to interact in affecting both average daily gain and feed conversion efficiency; littermates in control pens had the highest performance, those regrouped in hide pens were intermediate and those in regrouped-control pen and littermates-hide pen treatment groups had the poorest performance.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4038700 TI - Raw soybeans for gestating swine. AB - An experiment was conducted to determine the influence of feeding ground raw soybeans to swine during gestation on reproductive performance for three consecutive parities. Sixty crossbred gilts were bred and randomly assigned to two dietary treatments with 30 gilts/treatment. The diets were formulated to contain 14% crude protein with either soybean meal (SBM) or raw soybeans (RSB) serving as the source of supplemental protein. All animals were fed in individual gestation stalls and were given 1.81 kg of feed/d. Upon entering the farrowing house at approximately 110 d of gestation, all animals, regardless of previous treatment, were fed the same lactation diet (15% protein corn-soybean meal diet) until the pigs were weaned (28 d). After completing three parities, 88 of a possible 90 litters were farrowed by each dietary group. Total number of live pigs at parturition and 21 d for three parities were: (SBM) 887, 732 and (RSB) 924, 765, respectively. Average pig birth and 21-d weights for each dietary group were (SBM) 1.52, 5.42 and (RSB) 1.59, 5.41 kg, respectively. Pigs from dams fed RSB had higher average pig birth weights (P less than .05), but weaning weights were not affected. There were no significant differences in maternal weight changes during gestation. Milk samples were collected within 6 h after parturition, 3 and 14 d of lactation. Percentage milk fat for each time period was: (SBM) 5.6, 9.0, 7.0 and (RSB) 6.3, 10.7, 6.5, respectively. Sows fed RSB had a higher milk fat at 3 d (P less than .05) but a lower milk fat at 14 d (P less than .1) than did the sows fed SBM. The study indicated RSB can be effectively utilized in gestation diets fed to swine. PMID- 4038702 TI - Cortisol response of gilts in tether stalls. AB - Several experiments were conducted to evaluate serum cortisol concentrations and the circadian rhythm of this hormone in gilts tethered in stalls. Control animals were penned individually. In the initial experiment, 18 nongravid gilts were placed in tether stalls after being in either tether stalls or individual pens for 2 wk. No significant differences were found in serum cortisol concentrations. In a second experiment, 16 ovariectomized gilts were placed in tether stalls or individual pens for up to 5 wk. Estrus was induced during wk 3 and 4. During the first day in tether stalls, serum cortisol concentrations increased (P less than .05) and the circadian rhythm of cortisol was disrupted for 4 d. During estrus, the circadian rhythm of cortisol was interrupted for several days in the gilts, regardless of housing. After 4 wk, morning concentrations of cortisol were higher for gilts in tether stalls. The results indicate that: 1) the initial response to tethering varies according to previous penning and handling experience, 2) although the circadian rhythm of cortisol was either altered or disrupted during estrus, such disruptions were not influenced by type of penning and 3) tether stalls may chronically increase cortisol concentrations in gilts. PMID- 4038703 TI - Management of cryptosporidiosis. PMID- 4038704 TI - Regulation of phenylalanine ammonia lyase in Rhodotorula glutinis. AB - In the red yeast Rhodotorula glutinis, phenylalanine ammonia lyase (PAL) was induced 10-fold during carbon starvation even in the absence of exogenous phenylalanine, although maximal induction occurred when phenylalanine was the nitrogen (40-fold) or carbon (100-fold) source. Apparent regulatory mutations that affected the expression of PAL were isolated by selecting mutants resistant to the analog p-fluoro-D,L-phenylalanine (PFP). One such mutant, designated FP1, could use phenylalanine as a nitrogen source but not as a carbon source. Similarly, FP1 failed to utilize intermediates of the phenylalanine degradative pathway, namely, benzoate, p-hydroxybenzoate, or 3,4-dihydroxybenzoate, as carbon sources. Although the PFP-resistant mutant contained a low level of PAL, no increase was found when it was grown with phenylalanine as the nitrogen source. A derivative of FP1, FP1a, was isolated that simultaneously regained an inducible PAL and the ability to use phenylalanine, benzoate, p-hydroxybenzoate, and 3,4 dihydroxybenzoate as carbon sources. In addition, when p-hydroxybenzoate was the carbon source, PAL was induced in the mutant FP1a but not in the PFP-sensitive parental strain. We propose that the mutation to PFP resistance occurred in a regulatory gene that controls the entire phenylalanine degradative pathway. Secondary mutations at this locus, as found in strain FP1a, not only restored expression of this pathway, but also altered the induction of PAL by metabolites of this pathway. PMID- 4038705 TI - Inhibition of lipases by proteins. A kinetic study with dicaprin monolayers. AB - We report further investigations on protein inhibition of pancreatic and microbial lipases carried out with the monolayer technique. When beta lactoglobulin A, melittin, serum albumin, myoglobin, and a protein inhibiting lipase from soybean were preincubated with a dicaprin film at a surface pressure of 35 dynes/cm, no activity was detected with horse pancreatic or Rhizopus delemar lipases. By contrast, Rhizopus arrhizus and Geotrichum candidum lipase activities were not impaired under the same conditions. Experiments using mixed lipid-protein film transfer clearly show that the inhibition of pancreatic lipase is due to the protein associated with lipid and not caused by direct protein enzyme interaction in the aqueous phase. Three parameters were used to determine the surface properties of the various proteins at the dicaprin/water interface; namely, the initial rate of surface pressure increase, (delta pi/delta t)t = 0, the maximal surface pressure increase, delta pi max, and the critical surface pressure, pi c. A positive correlation was observed between values of (delta pi/delta t)t = 0 of proteins and their respective capacity to inhibit pancreatic and R. delemar lipases. By contrast, there was no apparent correlation with the two other parameters, delta pi max or pi c. PMID- 4038706 TI - Effect of bilayer cholesterol content on reconstituted human erythrocyte sugar transporter activity. AB - The influence of altered bilayer cholesterol content on the catalytic activity of the human red cell hexose transporter was examined by reconstitution of the transport protein (band 4.5) into bilayers of large unilamellar vesicles formed from dipalmitoyl lecithin and varying amounts of cholesterol. The physical state of the bilayers was characterized by differential scanning calorimetry. The major findings are as follows: changes in bilayer phase behavior occur at membrane cholesterol levels of 15 to 20 mol % and 30 to 40 mol %; and the catalytic activity of the reconstituted transporter (Vmax/transporter) correlates with bilayer phase behavior. In crystalline bilayers, this is seen as an abrupt, stimulation of activity at 15 mol % cholesterol (which is reversed at 17.5 mol %) and a gradual acceleration of activity between 30 to 40 mol % cholesterol. In fluid bilayers (where activity is high), activity is unaffected by 10, 20, and 30 mol % cholesterol. However, 12.5 and 17.5 mol % cholesterol reduce activity by 100-fold. These studies demonstrate that small changes in bilayer cholesterol content result in drastic alterations in transporter activity. Transporter sensitivity to cholesterol is a complex rather than monotonic function of bilayer cholesterol content and appears to be primarily determined by bilayer composition rather than by bilayer "fluidity." PMID- 4038707 TI - Initiation of DNA replication at the primary origin of bacteriophage T7 by purified proteins. Initiation of bidirectional synthesis. AB - Replication of bacteriophage T7 DNA initiates in vivo at an origin located 15% of the distance from the genetic left end of the chromosome. Bidirectional DNA synthesis from this site results in complete replication of the chromosome. The combination of T7 RNA polymerase, T7 DNA polymerase, and T7 gene 4 protein initiates DNA synthesis in vitro within the cloned origin sequence (Fuller, C. W., and Richardson, C. C. (1985) J. Biol. Chem. 260: 3185-3196). DNA synthesis is primed by T7 RNA polymerase transcripts, and proceeds in the same direction (rightward) as transcription to yield partially replicated Y-form DNA molecules. The DNA product of in vitro synthesis (Y-form DNA) has been characterized by electron microscopic, sedimentation, and gel electrophoretic analyses. These studies show that Y-form DNA is the product of unidirectional replication of both leading and lagging strands from the origin to the right-hand end of the template. The inclusion of either Escherichia coli single-stranded DNA-binding protein or the functionally similar T7 gene 2.5 protein results in marked stimulation of bidirectional synthesis. Studies using purified Y-form DNA provide direct evidence that this species is an intermediate in the complete replication of the linear template. Purified Y-form DNA is converted to linear DNA in a reaction catalyzed by T7 DNA polymerase, T7 gene 4 protein, and single-stranded DNA-binding protein. Y-form DNA is a competent, transient intermediate during the bidirectional replication of linear DNA molecules and DNA-binding protein is essential to initiate leftward synthesis. PMID- 4038708 TI - Quaternary structure and composition of squash NADH:nitrate reductase. AB - NADH:nitrate reductase (EC 1.6.6.1) was isolated from squash cotyledons (Cucurbita maxima L.) by a combination of Blue Sepharose and zinc-chelate affinity chromatographies followed by gel filtration on Bio-Gel A-1.5m. These preparations gave a single protein staining band (Mr = 115,000) on sodium dodecyl sulfate gel electrophoresis, indicating that the enzyme is homogeneous. The native Mr of nitrate reductase was found to be 230,000, with a minor form of Mr = 420,000 also occurring. These results indicate that the native nitrate reductase is a homodimer of Mr = 115,000 subunits. Acidic amino acids predominate over basic amino acids, as shown both by the amino acid composition of the enzyme and an isoelectric point for nitrate reductase of 5.7. The homogeneous nitrate reductase had a UV/visible spectrum typical of a b-type cytochrome. The enzyme was found to contain one each of flavin (as FAD), heme iron, molybdenum, and Mo pterin/Mr = 115,000 subunit. A model is proposed for squash nitrate reductase in which two Mr = 115,000 subunits are joined to made the native enzyme. Each subunit contains 1 eq of FAD, cytochrome b, and molybdenum/Mo-pterin. PMID- 4038711 TI - Regression analysis of data with correlated errors: an example from the NHLBI twin study. AB - Epidemiologic studies often involve genetically related individuals, spouses, or repeat observations on the same individual. When regression analysis is required in such studies, significant correlation of the residuals may affect the estimates of the standard errors of the regression coefficients. Ordinary least squares may not provide the best (minimum variance) estimates of the regression coefficients. Generalized least squares (weighted least squares) is more appropriate when the covariance matrix of the errors is known or can be estimated with some degree of confidence. Data from a twin study of pulmonary function were analyzed by three different regression techniques and comparisons of the coefficients and standard errors are made to illustrate the potential effects of correlated errors. PMID- 4038710 TI - Lymphocyte mechanical response triggered by cross-linking surface receptors. AB - Using a recently developed method (Petersen, N. O., W. B. McConnaughey, and E. L. Elson, 1982, Proc. Natl. Acad. Sci. USA., 79:5327-5331), we have measured changes in the deformability of lymphocytes triggered by cross-linking cell surface proteins. Our study was motivated by two previously demonstrated phenomena: the redistribution ("capping") of cross-linked surface immunoglobulin (sIg) on B lymphocytes and the inhibition of capping and lateral diffusion ("anchorage modulation") of sIg by the tetravalent lectin Concanavalin A (Con A). Both capping and anchorage modulation are initiated by cross-linking cell surface proteins and both require participation of the cytoskeleton. We have shown that the resistance of lymphocytes to deformation strongly increased when sIg or Con A acceptors were cross-linked. We have measured changes in deformability in terms of an empirical "stiffness" parameter, defined as the rate at which the force of cellular compression increases with the extent of compression. For untreated cells the stiffness was approximately 0.15 mdyn/micron; for cells treated with antibodies against sIg or with Con A the stiffness increased to approximately 0.6 or 0.4 mdyn/micron, respectively. The stiffness decreased after completion of the capping of sIg. The increases in stiffness could be reversed to various extents by cytochalasin D and by colchicine. The need for cross-linking was demonstrated by the failure both of monovalent Fab' fragments of the antibodies against sIg and of succinylated Con A (a poor cross-linker) to cause an increase in stiffness. We conclude that capping and anchorage modulation involve changes in the lymphocyte cytoskeleton and possibly other cytoplasmic properties, which increase the cellular viscoelastic resistance to deformation. Similar increases in cell stiffness could be produced by exposing cells to hypertonic medium, azide ions, and to a calcium ionophore in the presence of calcium ions. These results shed new light on the capabilities of the lymphocyte cytoskeleton and its role in capping and anchorage modulation. They also demonstrate that measurements of cellular deformability can characterize changes in cytoskeletal functions initiated by signals originating at the cell surface. PMID- 4038709 TI - Comparison of Ca++-regulated events in the intestinal brush border. AB - The intestinal epithelial cell and specifically the cytoskeleton of the brush border are thought to be controlled by micromolar levels of free calcium. Calcium binding proteins of this system include intestinal calcium binding protein (CaBP), calmodulin (CaM), villin, and a 36,000-mol-wt protein substrate of tyrosine kinases. To assess the sequence of events as the intracellular Ca++ level rises, we determined the amount of CaM and CaBP in the intestinal epithelium by western blotting and tested the Ca++ binding of CaM and CaBP by equilibrium dialysis. The Ca++-dependent actin severing activity of villin was analyzed in the presence of physiological CaM levels and increasing calcium concentrations. In addition, we analyzed the Ca++ levels required for interaction between CaM and the microvillus 110,000-mol-wt protein as well as fodrin and the interaction between a polypeptide of 36,000 mol wt (P-36) and actin. The results suggest that CaBP serves as the predominant Ca++ buffer in the cell, but CaM can effectively buffer ionic calcium in the microvillus and thus protect actin from the severing activity of villin. CaM binds to its cytoskeletal receptors, 110,000 mol-wt protein and fodrin differently, governed by the free Ca++ and pH. The interaction between P-36 and actin, however, appears to require an unphysiologically high calcium concentration (10(-4) to 10(-3) M) to be meaningful. The results provide a coherent picture of the different Ca++ regulated events occurring when the free calcium rises into the micromolar level in this unique system. This study would suggest that as the Ca++ rises in the intestinal epithelial cell an ordered sequence of Ca++ saturation of intracellular receptors occurs with the order from the lowest to highest Ca++ requirements being CaBP less than CaM less than villin less than P-36. PMID- 4038712 TI - Diurnal hypersecretion of growth hormone in depression. AB - A 24-h profile of plasma GH concentrations was obtained together with polygraphic recordings of sleep in 16 men suffering from a major depressive disorder (8 unipolar and 8 bipolar) and in 8 age- and sex-matched normal men. None of the patients had any physical illness. All were studied after a drug-free period of at least 15 days. Blood was sampled every 15 min. The amount of GH released in every significant secretory spike was estimated using a computer program. Both unipolar and bipolar depressed patients secreted more GH than normal men (mean +/ SD, 441 +/- 189 micrograms/24 h for unipolar depressed men; 357 +/- 143 micrograms/24 h for bipolar depressed men vs. 172 +/- 101 micrograms/24 h for normal men (P less than 0.01). This hypersecretion occurred during waking hours rather than during sleep. The increase in daytime GH release was more marked in unipolar depressed patients. During sleep, depressed patients and normal men secreted similar amounts of GH despite an overall reduction in slow wave stages in depressed patients. An early sleep GH increase was found in all but one of the normal men, but was absent in seven of the eight unipolar depressed patients, who had, instead, a presleep increase in between 2100-0000 h. No consistent disturbance of the temporal association between sleep onset and GH secretion was found in bipolar depressed patients. PMID- 4038713 TI - Pituitary-testicular axis dysfunction in burned men. AB - Plasma total testosterone, free testosterone, LH, and sex hormone-binding globulin (testosterone-estradiol-binding globulin) were measured in adult men hospitalized for treatment of burns. Total testosterone was below the normal range in 37 of 41 patients. Free and total testosterone levels declined very rapidly after the burn, remained low for weeks, and rose toward the end of hospitalization, but usually had not reached normal levels at discharge. The more severe the burns, the lower were the testosterone levels. LH levels were below normal during the first 4 days after the burn and remained in the low or mid normal range thereafter. Sex hormone-binding globulin levels were normal or slightly low. The data suggest the presence of a central defect in the release of LH. Large doses of opiate analgesics or an increase in endogenous opiate peptides related to severe persistent pain might be contributing factors to the pituitary testicular hypofunction found in burned men. PMID- 4038714 TI - The concurrence of hypoparathyroidism provides new insights to the pathophysiology of X-linked hypophosphatemic rickets. AB - Controversy exists over the role that PTH and extracellular fluid calcium concentration may play in modulation of the renal phosphate transport defect in X linked hypophosphatemic rickets. In previous studies, administration of PTH to affected subjects resulted in an increase or no effect on renal phosphate excretion, while calcium infusion increased renal tubular phosphate transport. In contrast, patients with X-linked hypophosphatemic rickets and hyperparathyroidism have no change in their renal phosphate wasting after parathyroidectomy. However, none of these were permanently hypoparathyroid postoperatively. We describe a patient with idiopathic hypoparathyroidism in whom we proved the coexistence of X linked hypophosphatemic rickets using family history and dental abnormalities. Initially, the patient had a mean serum calcium level of 5.6 +/- 0.07 (+/- SE) mg/dl and a renal tubular maximum for reabsorption of phosphate per liter glomerular filtrate (TmP/GFR) of 6.5 +/- 0.46 mg/dl. Hypoparathyroidism was confirmed, and therapy with vitamin D (50,000 U/day) and calcium (1,000 mg/day) was begun. On this regimen, serum calcium rose to 8.1 +/- 0.2 mg/dl, and TmP/GFR declined to 2.59 +/- 0.12 mg/dl. Bone biopsy revealed the persistence of osteomalacia. Subsequently, therapy with 1,25-dihydroxyvitamin D3 (1.0 microgram/day) was initiated, and serum calcium rose to 9.6 +/- 0.07 mg/dl, and TmP/GFR declined to 1.79 +/- 0.16 mg/dl. The prevailing serum calcium level correlated inversely with the TmP/GFR (r2 = 0.91; P less than 0.001). These data indicate that calcium and/or PTH are involved in modulation of the renal phosphate transport defect in X-linked hypophosphatemic rickets. PMID- 4038715 TI - Homologous and heterologous growth hormones fail to stimulate avian cartilage growth in vitro. AB - Recent reports that GH has a direct effect on growing cartilage have raised questions as to the role of somatomedins (Sm) in cartilage growth. To test the hypothesis that GH directly stimulates cartilage growth, we added homologous and heterologous GHs to organ cultures of embryonic chick pelvic cartilage. Pelvic rudiments from 9-day-old chick embryos were incubated in serum-free medium for 3 days in medium alone or medium containing chicken GH, turkey GH, bovine GH, human GH, and bovine GH produced by recombinant DNA methodology. None of the GH preparations studied stimulated avian cartilage growth in vitro. However, cartilage wet weight increased in response to sera from normal and growth hormone treated hypophysectomized rats. In addition, 20 ng/ml purified Sm-C caused a 78% increase in cartilage weight above that of cartilage incubated in medium alone. Insulin also caused an increase in cartilage weight, but in concentrations 50,000 100,000 times that of Sm-C. Our studies demonstrate that homologous and heterologous GH have no effect on growing avian cartilage and support the hypothesis that Sm directly mediate cartilage growth. PMID- 4038716 TI - Changes in sex hormone-binding globulin binding capacity and percent free estradiol during development in the female rhesus monkey (Macaca mulatta): relation to the metabolic clearance rate of estradiol. AB - Circulating sex hormone-binding globulin (SHBG) binding capacity and percent free estradiol (% free E2) were measured in separate groups of female rhesus monkeys from 2 months of age through adulthood (greater than 4.5 yr old). The SHBG concentration alone was also measured in 11 adult and 6 sexually immature animals on the same day as the blood MCR of E2. Serum SHBG levels were the highest (range, 12-25 micrograms T/dl) and the % free E2 the lowest (0.88%) in animals 6 months old or less. After the age, serum SHBG binding capacity declined generally at an average rate of 0.11 SHBG U (microgram T/dl)/month toward a nadir in adulthood. There was no difference in the SHBG levels in the follicular or luteal phase of the menstrual cycle. The relative blood MCR E2 and circulating SHBG binding capacity were significantly greater (P less than 0.001) in the sexually immature animals [MCR E2, 48.4 +/- 5.2 (SEM) liters/day . kg body wt; SHBG, 9.8 +/- 1.0 microgram T/dl, n = 6] than in adult animals (MCR E2, 27.7 +/- 1.7 liters/day kg body wt; SHBG, 4.6 +/- 0.3 microgram T/dl, n = 11). There was no relation between the MCR E2 and circulating SHBG levels within each group of adult or immature animals. The mean % free E2 doubled (to 1.6%) between 1 and 54 months of age; there was no relation between total circulating E2 and % free E2. Although a high SHBG binding capacity and a low % free E2 in the circulation of the immature animal does not inhibit the metabolic clearance of E2; it remains possible that these factors (and others) may hinder the access of E2 to reproductive target tissues and thereby contribute to the slow acquisition of reproductive competence in this species. PMID- 4038717 TI - Detection of methionine-enkephalin at the 10(-16) mole level. AB - A high performance radioimmunoassay for Met5-enkephalin has been developed, using two ways to circumvent the difficulties of obtaining such an assay for the opiate peptides. First, hemocyanin was used as the carrier for the antigen and secondly, a new iodination method for Met5-enkephalin was established, resulting in a [125I]probe with an intact methionyl residue. The Met5-enkephalin antibodies exhibited a very high affinity (Kd = 5 X 10(-12) M) and Met5-enkephalin could be detected at the 10(-16) mole level. The Met5-enkephalin content of individual cervical ganglia and individual cochlea was measured. We also measured the Met5 enkephalin content of brain from different areas of two rat strains: no significant differences were found. PMID- 4038718 TI - Masson's pseudoangiosarcoma of the tongue: report of two cases. AB - Two cases of Masson's vegetant intravascular hemangioendothelioma localized on the tongue are reported. This lesion has sometimes been confused histologically with angiosarcoma but always behaves in a benign fashion. PMID- 4038719 TI - Clinical improvement in hypertrophic cardiomyopathy after inferior myocardial infarction. AB - In cases of hypertrophic cardiomyopathy, the pathophysiologic role of the systolic pressure gradient across the left ventricular outflow tract is the subject of continued controversy. A patient with this disorder is described whose symptoms and provokable intraventricular gradient disappeared after inferior myocardial infarction. Diastolic left ventricular pressures were essentially unchanged, the isovolumic relaxation period became prolonged and the ejection fraction decreased from 0.77 to 0.61 after infarction. The peak ejection rate was unchanged, but the disappearance of systolic anterior motion of the mitral valve leaflet and obstructive manifestations may have resulted from enlarged mid to late systolic ventricular volumes. This case suggests a direct relation between symptoms and intraventricular pressure gradient in certain patients with hypertrophic cardiomyopathy. PMID- 4038720 TI - Progesterone and luteinizing hormone secretion following stress-induced interruption of constant estrus in aged rats. AB - Concentrations of progesterone and luteinizing hormone (LH) were measured during the first diestrus and subsequent proestrus after constant estrous was interrupted by restraint stress. Stress stimulated an acute increase in serum progesterone. Although stress resulted in changes in vaginal cytology characteristic of normal estrous cycles, stress-treated constant estrous (CE) rats had no midcycle (diestrous day 1) elevation of progesterone and markedly lower LH and progesterone during the afternoon of proestrous than age-matched normally cycling controls. The majority of the treated rats resumed CE without completing a cycle. In a separate experiment, progesterone injection during proestrous resulted in increased LH secretion in aging rats with normal estrous cycles. These data indicate that decreased proestrous progesterone secretion may contribute to the decrease in neuro-endocrine stimulation of proestrous gonadotropin secretion in the aged rat and may be associated with the initiation of CE. PMID- 4038721 TI - Experimental infection of hamsters with Campylobacter jejuni. AB - Campylobacter jejuni is a major cause of diarrhea and enterocolitis in humans and animals. A mammalian model has been developed for studying pathogenesis of the disease in hamsters by colonizing the ileum and cecum with C. jejuni via either oral intubation after purgation or direct surgical inoculation into the cecum. This colonization resulted in production of disease including diarrhea and intestinal lesions that resembles enterocolitis due to C. jejuni in humans and domestic animals. The mucosal lesions observed grossly at autopsy included erythema of the ileum and cecum and distention of the cecum with fluid. The cecal mucosa was edematous. Epithelial lesions observed by light microscopy included focal edema, occasional hyperplasia, diffuse hyperemia, and infiltration of the lamina propria with leukocytes. C. jejuni-like bacteria penetrated the epithelium and were observed within the lamina propria of infected animals but not in uninfected controls. PMID- 4038722 TI - [Studies on combined effect of hyperthermia and MTX to choriocarcinoma cell line (BeWo)]. AB - Changes in cell growth and hormone production of the choriocarcinoma cell line BeWo were studied to determine the manner in which the change in the cell cycle due to antimetabolite MTX affects heat sensitivity. First of all, BeWo was treated with 10(-7)M-MTX for 48 hrs. on day 4. And heat (43 degrees C for 1 h.) was applied at various stages after MTX removal on day 6. At the same time, the change in the cell cycle induced by MTX was studied by autoradiography. The labeling index (L.I.), which was increasing until 90% by MTX exposure, still remained more than 80% up to 5 hrs. after MTX removal and then decreased to about 43% at 9 hrs. after MTX removal. The greatest effect on cell growth and HCG production was seen when heat was applied within 5 hrs. after MTX removal. And these 5 hrs. corresponded to the time when the L.I. was as high as 80 to 90%. When heat was applied more than 6 hrs. after MTX removal, the heat sensitivity was reduced in proportion to the degree of decrease in the L.I. These findings suggest that the change in the cell cycle induced by MTX has the greatest effect on the heat sensitivity of BeWo. It is therefore possible to conclude that synchronization of BeWo with S phase by using MTX or possibly other antimetabolites is very important in the application of hyperthermia. PMID- 4038723 TI - [A summary of the experience with cisplatin in the treatment of gynecological malignancies, with special reference to advanced ovarian cancer]. AB - This report summarizes the results on the evaluation of Cisplatin in gynecological malignancies. A total of 51 evaluable cases, comprises 29 of which were advanced or recurrent ovarian cancer and 22 of other gynecological malignancies. The main results are summarized as follow: The overall efficacy rate was 58.3% on ovarian cancer and 13.6% on other malignancies. Seen histologically, almost the same good overall efficacy rates were obtained in all types except for the mesonephroid type. When Cisplatin therapy is used in combination with surgery, the preoperative use provides a higher efficacy rate (68.2%) than the postoperative use (28.6%). Also cases with a Second Look Operation showed a much higher one year survival rate (80.0%) than those of the cases without S.L.O. (25.0%). From these results, it is deduced that Cisplatin is the most useful agent for induction chemotherapy for S.L.O. on advanced ovarian cancer. The side effects observed were milder than those of anti-cancer drugs known so far with the usual dosage, and no fetal damage was observed. PMID- 4038724 TI - [Correlation between progesterone and plasminogen activator in rat ovaries during the ovulatory process]. AB - The role of progesterone in the action of hCG on follicular rupture is unclear at present. In this present study, we investigated the correlation between the preovulatory increase in progesterone and the periovulatory increase in plasminogen activator (PA) activities was completely suppressed with simultaneous injection with hCG of a minimum effective dose of cycloheximide to block ovulation completely. Suppression of hCG-induced acute rise of preovulatory progesterone after simultaneous injection with hCG of a minimum effective dose of cyanoketone to block ovulation completely, was accompanied by an only partial but significant suppression of hCG-induced increase in PA activities. Furthermore this suppression of PA activities after concurrent injection of cyanoketone with hCG was reversed by a supplementary injection of a dose of progesterone which was enough to restore ovulatory responses completely against the inhibitory action of cyanoketone. These facts suggest that PA in rat ovaries is synthesized de novo and progesterone may be responsible for the increase of PA in rat ovaries during the periovulatory process. PMID- 4038725 TI - [Methodological study for human in-vitro fertilization related to maturity of gametes]. AB - The correlations with maturity of gametes and fertilizability was studied. Specimens of semen were treated by several methods for induction of capacitation and acrosome reaction (AR). Follicular oocytes were recovered with endoscopic aspiration procedures, and divided to two groups: 1, maturing in vivo (preovulatory) and 2, immature. Immature oocytes were divided further into two subgroups: 1, germinal vesicle breakdown (GVBD) and 2, first polar body formation (FPB), after maturation culture. The sperms treated with the centrifuge trypsinization-layering method showed a higher incidence of in-vitro fertilization (69.2%) and cleavage (51.3%) of human preovulatory eggs compared with other capacitation inducing methods. It was found that human spermatozoa that have undergone the acrosome reaction prior to zona attachment are capable of fertilizing eggs under the in vitro conditions. On the estimation of fertilizability with reference to egg maturity, 52.5% (21/40) of IMIV-GVBD and 64.7% (22/34) of IMIV-FPB eggs were fertilized. However, only 12.5% (5/40) of IMIV-GVBD and 11.8% (4/34) of IMIV-FPB eggs cleaved. These results showed that IMIV eggs had fair fertilizability, but no developmental capacity after the first cleavage. This may due to prematurity of the cytoplasm in IMIV eggs. PMID- 4038726 TI - Acute and latent mastoiditis in children. AB - During the period from 1974 to 1981, surgery for acute mastoiditis was performed on 12 ears, giving an annual incidence of 0.004 per cent among cases of acute otitis media. All ears made a full long-term recovery. The low incidence is ascribed to the world-wide early use of antibiotics. During the same period 52 ears with secretory otitis media (SOM) underwent mastoidectomy. Histologically extensive mastoid inflammation was found in 96 per cent. The changes appeared as formation of secretory cells and cysts, resorption of bone, and infiltration of soft tissues with both mononuclear cells and polymorphonuclear leucocytes. The number of SOM patients undergoing mastoid operations account for 1.4 per cent of the patients admitted to hospital because of SOM. Thirty-four ears (65 per cent) have healed during the follow-up period (mean 2.9 years), while the tympanostomy tube is still in place in 18 ears (35 per cent). In the latter group, factors causing oedema in the pharyngeal end of the Eustachian tube are apparently still present. PMID- 4038728 TI - Hypertrophic cardiomyopathy in childhood: Part I. PMID- 4038727 TI - Evaluation of the contribution of dietary cholesterol to hypercholesterolemia in diabetic rats and of sitosterol as a recovery standard for cholesterol absorption. AB - The contribution of dietary cholesterol to hypercholesterolemia in diabetic rats fed chow ad libitum was evaluated. Diabetes was induced with streptozotocin, and the intake, absorption, and subsequent tissue distribution of dietary cholesterol were measured. Absorption was measured as the difference between [3H]cholesterol intake and fecal 3H-labeled neutral sterol excretion, using both [14C]sitosterol (added to diet) and [14C]cholesterol (added to feces) as recovery markers. [3H]Cholesterol absorption was underestimated by 1-3% using [14C]sitosterol as a recovery standard, due to the 7-8% absorption of sitosterol. After 3 weeks of diabetes, rats were hyperphagic, thereby increasing dietary cholesterol intake 2 fold. [3H]Cholesterol absorption was significantly increased from 69% in controls to 78% in diabetics, whereas [14C]sitosterol absorption was unaffected. With increased dietary cholesterol intake and decreased whole body cholesterol synthesis (Diabetes. 1983. 32: 811-819), influx from diet equaled for exceeded influx from synthesis. The amounts of 3H-labeled neutral sterol recovered from the small intestine, periphery, and plasma were increased 3- to 4-fold in the diabetic rats. Furthermore, the degree of hypercholesterolemia in diabetic rats was directly related to the fraction of plasma cholesterol derived from the diet. We conclude that the 2.3-fold increase in absorbed dietary cholesterol resulting from hyperphagia and, to a lesser extent, from increased fractional absorption, contributes to the hypercholesterolemia of diabetic rats fed chow ad libitum. PMID- 4038729 TI - Effects of restricted maternal contact in neonatal rats on sexual behaviour in the adult. AB - Rats, deprived of maternal contact and nutrition every alternate day starting on day 5 of life, attained a body weight at 45 days of age which was 50% of that of rats which had free access to maternal contact and nutrition. After 55 days of unrestricted food availability the body weight of the neonatally deprived rats was approximately 15% lower than that of the controls. Malnourished female rats showed normal behavioural oestrous cycles and became pregnant and lactated normally as young adults. After ovariectomy they showed higher lordosis quotients in response to treatment with oestradiol benzoate and progesterone than controls but lost less body weight in response to treatment with oestradiol-filled constant-release implants. Malnourished male rats ejaculated less frequently than controls in tests with sexually receptive female rats but this difference disappeared with repeated testing. The malnourished males showed longer ejaculation latencies and had somewhat higher serum concentrations of LH than controls after castration and treatment with testosterone-filled constant-release implants which reduced serum androgen concentrations to about 30% of the intact level. The results show that rats are capable of sustaining a rather severe neonatal nutritional deprivation without losing the capacity for essentially normal mating behaviour in adulthood. PMID- 4038730 TI - Methylphenidate and idiopathic thrombocytopenic purpura--is there an association? PMID- 4038731 TI - Annual testicular cycle of the lizard Anolis carolinensis: effects of pinealectomy and melatonin. AB - The effects of pinealectomy and exogenous melatonin treatment on the reproductive system of male anoles were examined at several different times of year. In September pinealectomy of anoles exposed to either a stimulatory LD 14:10 light cycle or a nonstimulatory LD 10:14 light cycle induced significant testicular growth and development over that observed in sham-operated anoles. At a nonphotosensitive time of year (December) pinealectomy also had a significant progonadal effect but no effect of pinealectomy was seen in February-March. Daily melatonin injections given either in the morning or afternoon (or both) failed to block gonadal growth either (1) in sham-operated or pinealectomized anoles exposed to LD 14:10 in the fall or (2) in pinealectomized lizards exposed to LD 10:14 in the fall. Continuous melatonin administration via subcutaneous silastic implants blocked the progonadal effects of pinealectomy in the winter (December). The results show that pinealectomy can have significant progonadal effects; these effects are seasonal but can encompass phases of the annual testicular cycle which are either photoperiod-dependent or temperature-dependent; and melatonin may be a reproductively active factor involved. PMID- 4038732 TI - Cortical reaction and zona hardening in mouse oocytes following exposure to ethanol. AB - Mouse oocytes were treated with 8% ethanol for 3-6 min. The rate and pathways of parthenogenetic activation, occurrence of cortical reaction, and zona solubility changes were assessed in alcohol-treated eggs. The incidence of parthenogenetic activation was greatest (91%) after 3-4-min exposure, and it was reduced (84%) after 5-6-min exposure to alcohol. Also, the rate of haploid single pronucleate parthenogenones decreased and the rate of fragmented ova increased with increase time of exposure to ethanol. Ultrastructural observations showed occurrence of cortical reaction, disappearance and subsequent reappearance of short microvilli. A slight damage occurred to the ER in alcohol-exposed ova. The zona dissolution assay utilizing alpha-chymotrypsin demonstrated decreased solubility of the zonae pellucidae after exposure to alcohol. The zona dissolution t50 increased from 0.5 2.5 min in nontreated unfertilized oocytes to about 4 h in activated ova. The t50 of in vivo fertilized eggs was 4 1/2 h. Empty zonae exposed to alcohol lysed at the same rate as nontreated control zonae did. The results indicate that activation of mouse oocytes with alcohol initiates completion of meiosis and triggers the cortical reaction, which results in subsequent hardening of the zona pellucida. PMID- 4038733 TI - An ovarian regression syndrome in the platyfish, Xiphophorus maculatus. AB - The highly inbred Coatzacoalcos (Cp) strain of the platyfish, Xiphophorus maculatus, was noted for a high percentage of infertile females (XX). The ovaries of approximately one-quarter of all females regress. The time of gonadal atrophy varied from before sexual maturation up to 11 months of age. The gonadotropic zone of the pituitary was hypertrophied in regressed females. Transplants of immature testes and ovarian tissue into the caudal musculature of regressed females and the subsequent maturation of the grafts demonstrated that the ovarian degeneration was not due to pituitary or hypothalamic malfunction or an autoimmune disease. The cause of the gonadal degeneration was apparently localized to the ovary itself. This phenomenon was never observed in males (XY). Regressed ovaries fell into two categories, designated types I and II, with all being characterized by the presence of ductlike structures which resembled male efferent ducts, lined by Sertoli cells. Type I ovaries bore a marked similarity to certain mammalian dysgenetic gonads, while type II ovaries contained many proliferating germ cells and could be compared to the human neoplasm termed gonadoblastoma. It is suggested that the physiological lesion responsible for the ovarian regression syndrome involves the processes that control the determination and differentiation of the germ cells similar to those found in human 46,XY gonadal dysgenesis. PMID- 4038734 TI - Isolation of intact sperm asters from fertilized sea urchin eggs. AB - We have developed a procedure for isolating intact sperm asters in quantity from fertilized sea urchin eggs. This procedure is based on detergent-extraction methods developed previously for the bulk isolation of mitotic apparatuses. Using this protocol it is possible to isolate sperm asters as soon as they appear in the fertilized egg or at any subsequent point in their brief existence. PMID- 4038735 TI - Serotoninergic system in scrapie-infected hamsters. AB - Hamsters inoculated with scrapie virus show a dramatic hypersensitivity to serotoninergic drugs, developing a behavioral syndrome not unlike that obtained with pharmacologically induced lesions of the raphe nuclei. In an attempt to explain the state of hypersensitivity and to determine whether or not serotoninergic neurons were targets of the scrapie virus, pre- and postsynaptic serotoninergic sites were studied in the cerebral cortices of scrapie-infected and sham-inoculated hamsters. [3H]Imipramine binding and the uptake of endogenous 5-hydroxytryptamine (5-HT, serotonin) in synaptosomes prepared from scrapie inoculated animals were not different from those of controls. This suggests integrity of the serotoninergic neurons in scrapie-infected hamsters. In contrast, affinity for the 5-HT1 receptor (which modulates inhibitory response) was diminished whereas that for the 5-HT2 receptor (which modulates excitatory response) was increased. This "imbalance" between the two receptors which is amplified in in vivo responses may account for the 5-HT hypersensitivity. The alteration in the affinity of the two postsynaptic 5-HT receptors supports the observation that scrapie virus alters cell plasma membranes. PMID- 4038736 TI - The combined effects of dietary protein and fat on prolactin in female rats. AB - A 3 X 3 factorial experiment was conducted to examine how protein content (8, 16 and 32% of kcals from casein) and fat content (12, 24 and 48% of kcals from corn oil) interact to influence prolactin homeostasis in female rats. Weanling Sprague Dawley rats were assigned to each of nine diets fed ad libitum. Dietary fat had no effect on the time of vaginal opening although first estrus occurred slightly earlier with high fat diets (P less than 0.05). Rats fed diets with protein at 8% of kcal showed a 2-wk delay in vaginal opening and first estrus. After 18-20 wk of feeding, serum and pituitary prolactin concentrations were determined after decapitation during the afternoon of proestrus or diestrus. Although serum prolactin was elevated at proestrus, there were no effects of fat or protein on the serum or pituitary prolactin. Another group of rats were fitted with jugular cannulae and treated with perphenazine, a potent prolactin-stimulating drug. Dietary fat or protein had no effect on prolactin secretion after perphenazine treatment. In the final experiment, rats fed each diet were treated with either i.p. saline or perphenazine followed by decapitation. The pituitary was removed 3 h later for determination of the amount of prolactin depleted from the pituitary. There was no effect of diet on the amount of pituitary prolactin depleted by perphenazine. No evidence was obtained that changes in dietary fat or protein concentration influence serum prolactin or its secretion in response to a provocative stimulus.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4038737 TI - The effect of diet on retention by the rat of iron from a radiolabeled casein test meal. AB - Previous work has shown that weanling rats fed a soy protein isolate (SPI)-based diet retained less iron from a casein test meal than did rats fed a casein-based diet. In the present work this diet effect was further investigated. In experiment 1 rats were fed either SPI-or casein-based diet (about 25 ppm Fe) for 13 d, fasted overnight, given a 59Fe-labeled casein-based test meal, and refed either the same or the other diet for 7 d. 59Fe retention was determined by the percent of ingested label retained after 7 d. SPI reduced 59Fe retention when fed prior to the test meal (52.5 vs. 61.5%, P less than 0.001) and also when fed following the test meal (50.8 vs. 63.2%, P less than 0.001). In experiment 2a, exposure of SPI to steam at 108 degrees C for 30 min did not lessen the observed diet effect. In experiment 2b rats were fed either an SPI-or casein-based diet, and casein test meals were fed as above on days 14, 35 and 56. The SPI-based diet reduced 59Fe retention from the casein test meal fed on d 14 (58.2 vs. 68.0%, P less than 0.005), for the meal on d 35 there was no difference, and for the final test meal rats fed SPI retained more 59Fe (53.0 vs. 40.2%, P less than 0.01). In experiment 3 lactalbumin was shown to decrease 59Fe retention to the same extent as SPI (54.9 and 53.4%) as compared to casein (73.3%), whereas neither rapeseed protein concentrate (68.8%) nor oxalic acid (72.2%) had any significant adverse effect.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4038738 TI - Effects of marginal zinc deficiency on subclinical lead toxicity in the rat neonate. AB - Influence of maternal dietary zinc intake on tissue distribution of lead and zinc in neonatal rats administered lead acetate by gavage during lactation was examined. Milk from dams fed a marginally deficient diet (6 micrograms Zn/g diet) contained a lower zinc concentration at the beginning of lactation than did that from control dams (30 micrograms Zn/g diet); no differences were seen by d 11 of lactation. Dams fed the deficient diet had lower plasma zinc values in comparison with pair-fed or ad libitum-fed dams and lower femur zinc concentration in comparison with pair-fed dams. Pups suckling marginally deficient dams had lower concentrations of zinc in plasma, femurs and kidneys although hippocampal and cerebellar zinc were unaltered. Body weights of pups from marginally zinc deficient dams were lower than those from ad libitum-fed dams, but similar to those from pair-fed dams. Lead ingestion had no effect on body weight. Marginally zinc-deficient pups had greater lead accumulation in blood, femurs, hippocampi and cerebella, but not kidney, than did zinc-adequate pups. Marginal zinc deficiency during lactation increases the body lead burden of suckling rats, an effect not attributable to increased transfer of lead into milk in response to suboptimal maternal zinc status. PMID- 4038739 TI - Neonatal blood cell count in health and disease. II. Values for lymphocytes, monocytes, and eosinophils. AB - The distribution of normal cell counts (the reference range) has been determined previously for circulating neutrophils in infants from birth to 28 days of age. We have determined the reference ranges for the absolute peripheral blood lymphocyte, monocyte, and eosinophil counts obtained from 393 infants in this same cohort. Furthermore, white blood cell counts were obtained from three groups of infants with perinatal complications previously shown to be associated with abnormal neutrophil values (ABO incompatibility, n = 82; maternal hypertension, n = 68; neonatal sepsis, n = 140) and compared with the derived reference ranges; significant alterations in the distribution of cell counts were found in each of these groups at different times. Our data provide reference ranges for lymphocyte, monocyte, and eosinophil counts in the neonatal period and evidence of the effect of specific perinatal events on these cell counts. PMID- 4038740 TI - Postcatheterization urethral strictures following cardiac surgery in children. AB - Ten children among 221 with congenital cardiac anomalies developed urinary symptoms after removal of urethral catheters, which were routinely inserted for monitoring purposes during and after cardiac surgery. Six children developed urethral strictures. Poor tissue perfusion concomitant with serious congenital cardiac anomalies, together with secondary urine infection in the presence of a urethral catheter, are proposed as significant factors in the causation of such strictures in children undergoing cardiac surgery. PMID- 4038741 TI - Fistula-in-ano in childhood: a congenital etiology. AB - In a comparative study of fistula-in-ano and perianal abscess, over a 12-year period, evidence is presented to suggest that fistula-in-ano in childhood has a congenital etiology. PMID- 4038742 TI - Synaptosomal cholesterol and phospholipid levels in several mouse strains differentially sensitive to ethanol. AB - The influence of chronic ethanol treatment on synaptosomal plasma membrane (SPM) cholesterol and phospholipid levels was determined in C57BL, Swiss Webster, DBA and BALB-C mice. A significant increase in SPM cholesterol after chronic ethanol treatment was observed only in C57BL mice. No change in either SPM cholesterol or C/P ratios was observed in the other three mouse strains tested, albeit all strains were rendered tolerant to ethanol as judged by ethanol-induced hypothermia, sleep time and blood ethanol upon awakening. It is concluded that an increase in SPM C/P ratio is not a necessary concomitant of behavioral or neurophysiological tolerance resulting from chronic ethanol consumption. In other studies, the possible relationship between SPM C/P ratios and initial neurosensitivity to ethanol was assessed in eight different mouse strains as well as two selected lines of mice. None of the individual mice had been tested previously with ethanol. No meaningful correlations could be made when the SPM C/P ratios of these strains were compared to either ethanol-induced sleep time, blood ethanol upon awakening or hypothermia. Therefore, genetic differences in SPM C/P ratios do not appear to be functionally related to phenotypic initial neurosensitivity to ethanol. PMID- 4038743 TI - Premenstrual syndrome. PMID- 4038744 TI - Etiology of cervical pregnancy. Association with abortion, pelvic pathology, IUDs and Asherman's syndrome. AB - Five cases of cervical pregnancy were treated with hysterectomy. In addition to previous pelvic pathology, iatrogenic interventions can be possible predisposing factors in this type of pregnancy. The association of cervical pregnancy and induced abortion, with traumatic curettage damaging the endometrium, rendering it unsuitable for nidation, is well documented. The two cases of severe intrauterine adhesions in our series suggest that partial or complete obliteration of the uterine cavity by such adhesions might be an important cause of cervical pregnancy. The presence of an IUD and the administration of hormonal therapy for the treatment of Asherman's syndrome might have contributed to our cases of cervical pregnancy. PMID- 4038745 TI - Prognostic value of tissue polypeptide antigen in urological neoplasia. AB - The prognostic importance of tissue polypeptide antigen (TPA) in urine samples of patients with urological cancers has been evaluated. TPA concentration correlated well both with the stage of the disease and survival. A simple score system was devised. There was very significant worsening of the prognosis with increasing score. PMID- 4038746 TI - Thromboxane synthetase inhibitors (TXSI). Design, synthesis, and evaluation of a novel series of omega-pyridylalkenoic acids. AB - A novel series of omega-pyridylalkenoic acids has been prepared by applying the Wittig reaction. Modifications were made in the omega-aryl moiety, the alkylene chain length, the alpha-methylene group adjacent to the carbonyl group, and the carboxyl group of the molecule. The compounds were tested as inhibitors of thromboxane synthetase in an in vitro assay and in ex vivo experiments with the rat. Most members of this new class of thromboxane synthetase inhibitors (TXSI) showed good activity in both assay systems. (E)-7-Phenyl-7-(3-pyridyl)-6 heptenoic acid (9c; CV-4151) was one of the most potent compounds in in vitro enzyme inhibition (IC50 = 2.6 X 10(-8) M) and, when orally administered, the most potent and long acting in the inhibition of blood thromboxane A2 production in the rat. New conceptual models I-III for the enzyme-substrate (prostaglandin H2, PGH2) and the enzyme-TXSI interactions are proposed for understanding the molecular design and structure-activity relations. PMID- 4038747 TI - Growing tips of embryonic cerebellar axons in vivo. AB - Few studies have focused on the transformation of growth cones to mature synaptic arbors. To study these events in developing axons in vivo, we have labeled growing cerebellar axons with horseradish peroxidase (HRP) in postnatal stages [Mason and Gregory, 1984]. This report will provide the first data on embryonic cerebellar axons, and will ask whether growth cones differ in tracts and in target tissue and what features characterize axons that enter the cerebellum in fetal periods. During the earliest embryonic (E) periods examined (E16-19), axons in tracts have enlarged growth cones with lamellopodia and short filopodia that contain small and large vesicles. In contrast, axons within the cerebellar anlage from E16-postnatal day (P) 5 have fine calibers with a minimum of branching, and have small tapered growing tips. If synaptic contacts are made by such growing tips, there is little concomitant change in their shape. As target cells from layers and as their dendrites extend (P5-P7), growing tips and synaptic boutons differentiate according to the type of synaptic arrangement in which they engage. Enlarged, irregular expansions of growing tips correspond to synaptic contacts with multiple dendritic partners and are filled with large and small clear vesicles. Filopodia arising from such swellings, like the small undifferentiated growing tips of the type seen on embryonic axons, contain a mixture of vesicle types but make simple synapses with single profiles. Many axons make both kinds of synaptic structures, especially during the period when maturing axons give rise to long filopodia. Thus, growing tips have immature forms long after synaptogenesis begins, and use filopodial structures to elaborate synaptic arrangements. This analysis should elucidate the changes in growth cone form and cytology that reflect cell-cell interactions during synaptogenesis. PMID- 4038748 TI - Initial intravenous cis-platinum therapy: improved management for invasive high risk bladder cancer? AB - Between August 1981 and December 1983, 50 patients with invasive high risk bladder cancer were treated initially with 100 mg. per m.2 cis-platinum intravenously in 2 doses with a 3-week interval, which was followed by definitive treatment (radiotherapy and/or cystectomy). High risk disease was defined on the basis of at least 2 of the following: invasion into or beyond the muscle (stages B2 to D1), grade III histology, large tumors and ureteral obstruction. Major symptomatic improvement was noted in 38 patients (76 per cent) after 1 to 2 doses of cis-platinum and 30 (60 per cent) had an objective response to cis-platinum. An objective response (complete or partial remission) was noted in 43 patients (86 per cent) after cis-platinum plus definitive treatment. The 12-month actuarial survival was 86 per cent and the 2-year actuarial survival was 80 per cent (although only 14 patients were entered in the study more than 2 years ago). The protocol was well tolerated, with nausea and vomiting being the most common side effects. There were no deaths related to treatment. Ten patients (20 per cent) died of cancer. The relevance of initial cis-platinum therapy in this management program is now being evaluated in a multicenter randomized trial. PMID- 4038750 TI - The surgical repair of posterior urethral strictures by the transpubic urethroplasty or pull-through technique. AB - The management of strictures of the posterior urethra is reviewed in 75 adults and 19 children. Of the patients 66 were treated by a perineal pull-through technique and 28 underwent a transpubic approach. The transpubic approach provided excellent exposure to the damaged urethra with minimal morbidity, and good results were obtained in 89 per cent of the children and 69 per cent of the adults. Three patients had partial incontinence postoperatively but 2 recovered completely after 6 months. With the perineal pull-through technique, good results were achieved in 80 per cent of the children and 66 per cent of the adults. Worsening of sexual function was not seen in either treatment group as a consequence of the operation. As a result of this experience the transpubic approach is preferred in cases of complex urethral strictures, cases in which the length of the damaged urethra exceeds 3 cm. or in small children, reserving the pull-through technique for low-lying urethral strictures less than 3 cm. long. PMID- 4038749 TI - Preliminary results of M-VAC (methotrexate, vinblastine, doxorubicin and cisplatin) for transitional cell carcinoma of the urothelium. AB - The M-VAC (methotrexate, vinblastine, doxorubicin and cisplatin) regimen was used to treat 25 patients with transitional cell carcinoma of the urothelial tract. Treatment consisted of monthly cycles of 30 mg. per m.2 methotrexate, followed 24 hours later by 3 mg. per m.2 vinblastine, 30 mg. per m.2 doxorubicin and 70 mg. per m.2 cisplatin, and concluded with repeat vinblastine and methotrexate on days 15 and 22. Significant tumor regression was noted in 71 per cent of the patients. Complete clinical remission was observed in 12 of 24 patients (50 per cent, 95 per cent confidence limits 30 to 70 per cent) with bidimensionally measurable indicator lesions, 6 of whom had pathological confirmation. After surgical exploration 4 patients required downstaging to a partial remission. The median duration of response has not yet been reached at 9.5 plus months, range 4.5 plus to 16 plus. Five patients (21 per cent) had a partial clinical remission for 4 to 8 plus months, 1 had a minor response for 4 months and 1 had stable disease for 11 months. All metastatic sites responded, including bone (6 of 8 cases), liver (3 of 5), locoregional (12 of 17) and intravesical (6 of 7) disease. Toxicity included moderately severe myelosuppression that resulted in nadir sepsis in 4 patients and a drug-related death in 1, mild to moderate anorexia, vomiting, alopecia and renal dysfunction. These preliminary results suggest that treatment with methotrexate, vinblastine, doxorubicin and cisplatin is extremely effective against locoregional and disseminated urothelial tract tumors, with the expectation (95 per cent confidence limits) of inducing objective tumor regression in 53 to 89 per cent of the cases. PMID- 4038751 TI - Management of urethral strictures. PMID- 4038752 TI - Reconstruction of the female urethra to allow intermittent catheterization for neurogenic bladders and urogenital sinus anomalies. AB - Three girls with a neurogenic bladder and vaginally placed urethral meatus are described. Reconstructive techniques to allow intermittent catheterization and successful undiversion are discussed. All 3 girls currently are continent on intermittent catheterization and have been followed for 1 to 3 years. PMID- 4038753 TI - Re: The importance of the cremasteric reflex in acute scrotal swelling in children. PMID- 4038754 TI - Recombinant plasminogen agent continues to show promise in trials. PMID- 4038755 TI - [Collapse of the blood-aqueous humor barrier following laser injury--preventive pharmacotherapy with prostaglandin inhibitors]. AB - Laser-induced collapse of the blood-aqueous barrier and the protective effect of different prostaglandin inhibitors were investigated in the animal study reported here. As a parameter of the barrier function, the protein concentration in the aqueous humor was measured using a micromethod. The anterior chamber of 90 eyes (45 rabbits) was tapped only once, 100 min after the laser procedure. The results prove that different prostaglandin inhibitors in a systemic or topical application form can effectively reduce disturbances of the blood-aqueous barrier after laser surgery. This is also of clinical relevance with regard to laser iridotomy or trabeculoplasty in glaucoma. PMID- 4038756 TI - [Laser gonioplasty in therapy-resistant acute closed-angle glaucoma]. AB - Technical details of gonioplasty by argon laser and the risk involved in cases of medically uncontrolled acute angle-closure glaucoma are discussed. PMID- 4038757 TI - [Thrombotic thrombocytopenic purpura]. AB - Thrombotic thrombocytopenic purpura (TTP) is an uncommon disorder which usually occurs in young adults. It is characterized by a pentad of clinical findings: fever, neurological abnormalities, renal dysfunction, microangiopathic hemolytic anemia and thrombocytopenia. The histological hallmark is the presence of platelet thrombi occluding the microcirculation of multiple organs. The etiology and pathogenesis of disseminated platelet aggregation are uncertain and obviously not uniform in individual patients. Experimental findings suggest that microthrombi may result from intravascular platelet activation or form secondarily at sites of vessel wall damage. The differential diagnosis of TTP includes the hemolytic uremic syndrome in which the microangiopathic changes are exclusively found in the kidneys. When untreated, TTP invariably runs a progressive and fatal course. In recent years, prognosis has been improved by new forms of therapy such as plasmapheresis or infusions of fresh frozen plasma which may lead to recovery in about 80% of patients. PMID- 4038758 TI - [Activation of lipid peroxides in the liver during hypokinesia and its prevention by antioxidants]. AB - Experiments on white rats showed that exposure to hypokinesia increased peroxidation of unsaturated fatty acids of lipids of cell membranes, decreased the content of sulfhydryl groups, and increased the content of disulphide groups. This was very marked during the first 4-7 days, i.e., during the time of a distinct stress-reaction. At later stages the rate of free radical processes decreased slightly. In the recovery period that followed 7-day hypokinesia lipid peroxidation in the rats gradually returned to normal. The initiation of free radical reactions during hypokinesia can be prevented by means of antioxidants (acetate tocopherol, sodium selenite) and syrepar. PMID- 4038760 TI - Characteristic faecal flora of NC mice. AB - The composition of faecal flora of NC mice was compared with that of CF #1 mice. NC- and CF #1-germfree (GF) mice were cage-mated with NC- or CF #1-conventional (CV) mice in an isolator. The faecal flora of these ex-GF mice was dependent on the recipient mouse strain modifying colonization by the donor mouse bacteria. Although NC- and CF #1-pups removed by hysterectomy were fostered to different strains, almost all these mice at 8 weeks old had a strain characteristic pattern of faecal flora regardless of the foster strains. In GF mice mono-associated with a Lactobacillus strain or a Bifidobacterium strain isolated from faeces of CV mice, the numbers of these bacteria in the stomach and small intestine of NC mice were lower than those of CF #1 mice. In GF mice associated with chloroform treated faeces of CV mice, and a Lactobacillus strain or a Bifidobacterium strain, the numbers of these bacteria in the stomach and all parts of the intestine of NC mice were considerably lower than those of CF #1 mice. These results suggested that the composition of faecal flora of NC mice were characteristic, i.e. the fact that the numbers of lactobacilli were low compared with CF #1 mice with ordinary faecal flora and the colonization of bifidobacteria, peptococcaceae and eubacteria on ES agar in NC mice intestine differed, was due to genetic factors. PMID- 4038759 TI - [Specificity of ultrastructural changes in the myocardium of rats after hypokinesia and irradiation]. AB - By electron microscopy and morphometry cardiomyocytes of 20 rats gamma-irradiated with a single dose of 180.6 microCi/kg and those of 20 rats exposed to hypokinesia for 10 days were examined. Visually the ultrastructural changes of cardiomyocytes were nonspecific. The morphometric examination revealed specific features of ultrastructural rearrangements in the nuclei and mitochondria of cardiomyocytes of rats on day 10 of hypokinesia and irradiation. PMID- 4038761 TI - Serum prealbumin and retinol-binding protein in the prealbumin-related senile and familial forms of systemic amyloidosis. AB - In a series of 13 elderly patients with proven prealbumin-related senile systemic amyloidosis (SSA), depressed serum prealbumin values (110.7 +/- 14.1 micrograms/ml) were found as compared to an age-matched control group (175.1 +/- 20.3 micrograms/ml). As expected, there was a significant correlation between serum prealbumin and serum retinol-binding proteins in both groups of patients. Patients with reactive amyloid protein AA amyloidosis had slightly depressed serum prealbumin concentrations, whereas patients with prealbumin-related familial amyloidosis of Swedish type had prealbumin values within normal limits. Since the serum levels of the acute phase reactants, haptoglobin and amyloid related serum protein AA, were higher in the group of patients with reactive amyloidosis than in patients with SSA, the depression of the prealbumin levels in SSA is not a result of inflammation. Since SSA is known to contain prealbumin, it is possible that a disturbed prealbumin metabolism in old age results in low prealbumin serum values and deposition of amyloid. PMID- 4038762 TI - Oestradiol and progesterone receptors in the pig oviduct during the oestrous cycle. AB - The concentrations of the tissue receptors for oestradiol (E) and progesterone (P) in the porcine oviduct at different stages on the oestrous cycle have been investigated by in vitro binding and exchange methods. Both hormones bound to specific cytoplasmic (Rc) and nuclear (Rn) receptor proteins with high affinity. The concentrations of ERc and ERn were two-fold higher in the ampulla as compared to the isthmus. The amount of ERc in the isthmic portion of the oviduct did not vary throughout the oestrous cycle. However, the ampullar ERc concentrations increased during prooestrus, showed a maximum at standing oestrus, thereafter decreasing. Significant variations in the amount of oviductal ERn were observed. Despite the differences in ERn amounts between segments, the concentration of ERn increased significantly during late prooestrus, attaining a three-fold elevation and remaining elevated during the period of standing oestrous and early luteal phase (days 3-4), thereafter returning to basal levels. No significant variations in the amount of isthmic PRc were found throughout the period studied. The ampulla, however, showed a significant increase in PRc concentrations during standing oestrus, thereafter decreasing. The concentrations of PRn in isthmus and ampulla were of about the same magnitude and varied significantly during the oestrous cycle, increasing in concentration from standing oestrous onwards. The temporal relationships between the variations in levels of oestradiol and progesterone receptors in oviductal tissues and those of the circulating plasma levels were established. The data obtained in this study suggest a relationship between the changes in the levels of oestradiol and progesterone oviductal binding during the first days of the oestrous cycle, and the gamete and embryo transport throughout the oviduct in the porcine species. PMID- 4038764 TI - Drinking behavior in the Colorado adoptee and twin sample. AB - Using a sample of adult Colorado twins, nontwin sibling pairs and pairs of unrelated adoptees reared together (N = 346), the extent of the similarity in drinking behavior within pairs was estimated. The analyses, which go beyond those possible with a study confined just to twins, suggest that some alcohol-drinking behaviors may be genetically influenced. However, the genetic variance appears to be primarily nonadditive so that it contributes more to differences than to similarities between first-degree relatives. Alternatively, although less likely, these results might suggest a special common environment for identical twins that is not present for fraternal twins, nontwin siblings or unrelated adoptees reared together. Environmental analyses indicate that both types of twins share a special family environmental similarity that is not shared by nontwin siblings. Environmental influences that affect individual differences in drinking behavior appear to contribute more to dissimilarity than to similarity. The results do not support the contention that being raised in the same family contributes substantially to similarity in characteristics of drinking behavior. PMID- 4038763 TI - Rapid method for quantitation of androgen binding protein in Sertoli cell cultures and its use for measurement of binding kinetics. AB - The accurate measurement of the kinetics of binding of 5 alpha dihydrotestosterone to the Sertoli cell specific protein, androgen binding protein (ABP), has been frustrated by the extremely rapid rate of dissociation of the ABP-dihydrotestosterone complex. We describe a rapid and highly sensitive assay suitable for ABP quantitation which utilizes DEAE Bio-Gel and [3H]dihydrotestosterone. The assay has been used to accurately measure the rate of dissociation (8.25 X 10(-4) s-1, t1/2 14 min) and the rate of association (2.04 X 10(5) M s-1) of the binding of [3H]dihydrotestosterone to rat ABP. The ratio of these rate constants is in perfect agreement with the equilibrium dissociation constant determined by Scatchard analysis (4.0 nM). This multipoint assay is extremely rapid such that binding can be measured at equilibrium, it has high precision (coefficient of variation 3%), and is particularly useful at low protein concentrations (50 ng/ml); furthermore, the assay background of nonspecific 3H-binding is extremely low (0.2%). Since at such low protein concentrations a 10 point Scatchard analysis can be performed on 1 ml culture medium containing as little as 3 fmol ABP, the assay is suitable for monitoring changes in ABP secretion resulting from manipulations of cells in culture. The assay which utilizes DEAE Bio-Gel A is compared to five alternative methods: the standard method of steady state gel electrophoresis, Dextran-coated charcoal assay, hydroxylapatite assay, DEAE filter assay, and radioimmunoassay. The DEAE Bio-Gel assay has advantages over all of these alternative methods. In summary, this new assay is particularly useful for monitoring temporal changes in the secretion of ABP, and the method is equally effective in quantitating ABP in rat, rabbit and hamster Sertoli cell cultures. PMID- 4038765 TI - Hemangiosarcoma complicating Paget's disease of the bone. AB - An 87-year-old man with Paget's disease of the left humerus was found to have a Paget's sarcoma upon pathologic examination of the left upper limb, which was disarticulated for severe pain and recurrent fractures. The histologic type of this tumor, a hemangiosarcoma, was unique among Paget's sarcomas. PMID- 4038766 TI - Human renal carcinoma: characterization of five new cell lines. AB - Five human renal carcinoma cell lines have been established in long-term tissue culture. Two of the cell lines, UM-RC-2 and UM-RC-3, produced clear cell tumors in athymic nude mice. The cell lines have been characterized by staining with oil red O, doubling time in vitro, and number of chromosomes. Although protein A assay reactivity of autologous combinations of patient's sera and tumor cells were seen with all five cell lines, similar binding was also found with autologous normal kidney cultures. However, the immune adherence assay demonstrated low titer autologous reactivity with two renal carcinoma cell lines but not with the corresponding normal kidney cultures. This strongly suggest host recognition of tumor-associated antigens. Characterization of cell surface antigens with murine monoclonal antibodies demonstrated shared reactivity between normal kidney tubular cells and renal carcinoma cells. Antibody A68.11 reacted strongly with all five cell lines. Antibody A80 bound to only UM-RC-3 and UM-RC 6. PMID- 4038767 TI - Is there a continuity of filaments in the sarcomere? PMID- 4038768 TI - [Microangiopathic hemolytic anemia associated with cancer]. PMID- 4038769 TI - [Association of bone marrow aplasia and pregnancy: new cases]. PMID- 4038770 TI - [Bad prognosis and lack of effective treatment--a danger for risk groups in chronic cryptosporidiosis]. PMID- 4038771 TI - Nocturnal feeding in the mouse--opiate and pineal influences. AB - Mice displayed daily rhythms in their basal and morphine-induced food intake, consuming significantly greater amounts of food at night. Non-invasive inhibition of the activity of the pineal gland by either exposure to a bright pulse of light or treatment with the L-amino-acid decarboxylase inhibitor, benserazide, reduced the elevated night-time food intakes. These effects on feeding were most evident on the first night the activity of the pineal was reduced. On subsequent nights light pulses had a diminished effect on basal and morphine-induced food intake. These results suggest that although the enhanced nocturnal food intake of mice may be modulated by pineal and opioid sensitive mechanisms, pineal activity is not essential for the expression of opioid-mediated feeding. PMID- 4038772 TI - Diuretic and natriuretic actions of extract prepared from rat erythrocytes. AB - Freeze-dried preparation of rat erythrocytes was extracted into distilled water and after heat treatment the extract was chromatographed on Sephadex G-25 column. The effluent fractions were pooled, freeze-dried, dissolved in Ringer's solution and bioassayed for diuretic and natriuretic responses in anaesthetized non diuretic rats. The active fractions potently enhanced urine output (about 9-fold control) and urinary sodium excretion (about 7-fold control). The responses started to develop after a lag period of approximately 10-20 min, peaked between 60-80 min post-injection and then diminished. The augmentation of sodium excretion persisted longer than the increased diuresis. The biological activity of the extract was retained after dialysis in a tube with nominal molecular weight cut-off below 1,000. PMID- 4038773 TI - Enhanced development of dispositional tolerance to methadone by desipramine given together with methadone. AB - Rats given 2-day oral administration of methadone (15 mg/kg, twice on day 1 and once on day 2) by gastric tube developed dispositional tolerance to methadone analgesia as demonstrated by a decrease in analgesic response and by an increase in methadone metabolism. The increased metabolism of methadone was evidenced by a decrease in brain concentration of 14C-methadone and increases in the percentages of total 14C in liver or urine as 14C-water-soluble metabolites (14C-WSM) after the rats were challenged with a test dose of 14C-methadone. Two-day pretreatment with a combination of desipramine (DMI) (10 mg/kg, ip) and methadone (15 mg/kg, po) enhanced the development of dispositional tolerance to methadone analgesia which was evidenced by a greater decrease in the brain concentration of methadone and a greater increase in methadone metabolism as compared to those changes in rats pretreated with only methadone. Repeated treatment with DMI alone neither decreased the analgesic effect of methadone nor stimulated methadone metabolism. It is suggested that DMI given together with methadone promoted the induction of methadone metabolism in the liver by prolonging the enzyme-stimulating state of methadone, thus enhancing the development of dispositional tolerance to methadone. PMID- 4038774 TI - Suppression of an ethanol withdrawal syndrome in rats by 3-hydroxybutyrate. AB - An ethanol withdrawal syndrome was elicited by withholding ethanol from physically dependent, male Sprague-Dawley rats. Ethanol dependence had been induced by intragastric administration of ethanol at a dosage of 9 to 15 grams per kilogram per day over a four-day period. Oral administration of 3 hydroxybutyrate, a compound which is elevated in blood of ethanol dependent rats and is a substrate of both the cerebral small-pool and large-pool Krebs-cycle, was effective in suppressing the tremulous component of the ethanol withdrawal syndrome. 3-Hydroxybutyrate did not function as a central nervous system depressant at the dose levels employed. PMID- 4038775 TI - Chorionic biopsy. PMID- 4038776 TI - Desferrioxamine and Alzheimer's dementia. PMID- 4038777 TI - Lower atrial natriuretic activity in the newborn versus adult rat. AB - Experiments were designed to compare the natriuretic activity contained within extracts of the atrial myocardium of the newborn and adult rat. Extracts prepared from adult rats (greater than 8 weeks of age) contained significantly greater natriuretic activity than extracts from newborn preweanling pups (19 days of age). Since it has been reported that the primary site of inappropriate sodium reabsorption by the newborn kidney during saline expansion is in the distal nephron and since the atrial natriuretic factor (ANF has been reported to inhibit sodium reabsorption in this region of the nephron, results of the current study are consistent with the hypothesis that the compromised ability of the newborn to excrete a sodium load is related to a deficiency of ANF. PMID- 4038780 TI - Cryptosporidiosis in tourists returning from the Caribbean. PMID- 4038778 TI - DNase I footprinting shows three protected regions in the promoter of the rRNA genes of Xenopus laevis. AB - Extracts prepared from Xenopus laevis oocytes contain a protein(s) which specifically protects three discrete regions of the RNA polymerase I promoter from digestion by DNase I. Protected region I, from nucleotide +15 to nucleotide 10, spans the site of transcription initiation. Protected region II extends from nucleotide -70 to nucleotide -100 relative to initiation, falling within a 42 base-pair sequence which is homologous to the 60/81-base-pair repeated elements which occur outside of the promoter in the spacer. Protected region III is upstream of region II, from nucleotide -120 to nucleotide -140. All three regions correlate with sequences known from deletion studies to be important for promoter function. Deletion mutants which retain either region I or regions II and III together footprint normally. Deletion of region III, however, reduces but does not eliminate footprinting on region II, suggesting either that one protein binds to both regions or that the proteins which bind to these sites interact with each other. PMID- 4038779 TI - Genotoxic effects of some organophosphorous pesticides. I. Induction of micronuclei in bone marrow cells in rat. AB - The genotoxic effects of 4 organophosphorous pesticides, i.e. ekatin, fenitrothion, methylparathion and phorate, were examined employing the micronucleus test in bone marrow cells of the rat. Methylparathion and phorate were found to be mutagenic, while ekatin was weakly mutagenic. The frequency of micronuclei induction by fenitrothion did not differ significantly from that noticed in negative control. PMID- 4038781 TI - Intravenous thrombolysis in acute myocardial infarction: a progress report. PMID- 4038782 TI - Smokeless tobacco and blood pressure. PMID- 4038783 TI - Premenstrual syndrome. PMID- 4038784 TI - The Thrombolysis in Myocardial Infarction (TIMI) trial. Phase I findings. PMID- 4038785 TI - Two homoeo box loci mapped in evolutionarily related mouse and human chromosomes. AB - The homoeo box is a 180-base pair (bp) DNA sequence conserved in Drosophila homoeotic genes, which regulate early development. These DNA sequences are present in open reading frames and have been identified in specific gene transcripts in Drosophila and Xenopus embryos; they possess structural features in common with genes encoding some DNA-binding proteins. Homologous homoeo box sequences have been detected in species ranging from insects and annelids to vertebrates. The high degree of sequence conservation (70-90%) among different species suggests a strong evolutionary relationship and implies a common role in embryonic development. To test this hypothesis, one approach we have used is to examine the patterns of genetic organization of homoeo box sequences in mouse and human for any similarities; the second approach is to localize the chromosomal map positions of homoeo box sequences in the two species. A similar genomic organization and chromosomal distribution of homoeo box sequences would argue for a conserved function and might shed light on their mechanism of action. Here, we describe experiments which show that two homoeo box loci map, respectively, to evolutionarily related regions on mouse chromosome 11 and human chromosome 17. PMID- 4038786 TI - [Ductectomy as diagnosis and treatment of galactorrhea without palpable lesions]. PMID- 4038787 TI - Catecholamine involvement in preovulatory LH release: reassessment of the role of epinephrine. AB - Adult female rats were implanted with permanent cannulae in the third ventricle of the brain and allowed to recover regular 4-day estrous cycles. They received intrajugular cannulae on the morning of proestrus and later between 12.00-13.00 h catecholamines - norepinephrine (NE; 5.3 or 15.9 micrograms), dopamine (DA; 5.3 micrograms), epinephrine (E; 5.3 or 15.9 micrograms) or vehicle (artificial CSF) were administered intraventricularly. Plasma LH levels were measured in blood samples obtained prior to and 10, 20, 30 or 60 min after catecholamine injections. While NE or DA failed to alter basal plasma LH levels, E evoked a significant 2-fold rise in plasma LH levels. Quite unexpectedly, however, infusion of E (18.5 micrograms) over a 30-min period during the critical period failed to either reverse the pentobarbital-blockade of ovulation or stimulate LH release. Prior suppression of E levels selectively with LY 78335 blocked the preovulatory LH surge and ovulation. However, intraventricular E failed to evoke LH release in these LY 78335-blocked proestrous rats, an observation suggestive of some alpha 1-adrenoreceptor blocking action of the drug. In contrast, the alpha 1-adrenoreceptor blocking action was not evident in the estrogen, progesterone-primed ovariectomized rats similarly pretreated with LY 78335. These studies show that (1) E-containing neurons in the hypothalamus may play an important role in the preovulatory LH release; (2) LY 78335 may exert inhibitory effects on preovulatory LH release, in part, by blocking alpha 1-adrenoreceptors, and (3) participation of NE and DA, if any, in evoking preovulatory LH release remains to be ascertained. PMID- 4038788 TI - Air embolism through a ventriculoatrial shunt during posterior fossa operation: case report. AB - An unusual complication of air embolism through a ventriculoatrial shunt occurred in a patient undergoing posterior fossa operation in the sitting position. Because ventriculoatrial shunts are uncommon, this potential complication may not be widely recognized. A case is presented and the clinical aspects are discussed. PMID- 4038789 TI - Distinctive structural and cytoskeletal properties of the long-surviving neurons in cell cultures of embryonic spinal cord. AB - A distinctive population of neurons survives for longer than 3 months in cell cultures of chick or rat spinal cord. These neurons form a minor proportion (1%) of the neurons initially developing in the cultures, but are the only ones to survive longer than 30 days in vitro. In addition to their longevity, they share important morphological and cytoskeletal characteristics, which render them distinctive as a group even in early cultures which contain numerous other neurons of short-term viability. Each long-surviving neuron projects one neurite of great length relative to its other neurites, or to those of the shorter-lived neurons, and the length of this neurite is maintained constant for many weeks in vitro. This well-defined morphological feature may indicate the lineage(s) of these neurons. Structurally these cells are very different to the shorter-lived neurons. They are rich in neurofilaments and contain very few microtubules, whereas the shorter-lived neurons contain few neurofilaments but many microtubules. These differences in cytoskeleton coincide exactly with the distinction between limited and prolonged survival in vitro, and the possibility is considered that cytoskeletal stability in the presence of numerous small inflows of calcium might underlie "hardiness" in vitro. The state of development of the long-lived neurons is considered in the context of their shared features, and it is suggested that they may provide a model in which the regulation of development of neuronal function can be analysed. PMID- 4038790 TI - [Primary empty sella. Clinico-radiologic considerations in 18 cases]. AB - 18 patients with "primary empty sella" were reviewed for this study. In 3 of them the sellar enlargement was discovered occasionally by performing skull radiographs for other reasons. The galattorrhea-dismenorrhea or amenorrhea syndrome and obesity were the most common clinical features. Endocrinological tests were normal in ten patients and abnormal in eight. Slight elevation of serum PRL was the most common record. 12 patients had enlarging of the sella turcica; in 4, only the floor was asymmetric and in 2 the sella was quite normal. In 5 patients C.T. without intra-thecal contrast was sufficient to discover the E.S. In 13 patients we performed C.T. cysternography by injecting in the lumbar subarachnoid space 8-10 ml of Iopamidolo 200. This is an excellent and safe technique to perform C.T. cysternography. PMID- 4038791 TI - High cesarean section rate: a new perspective. AB - Cesarean section rates in the United States have increased dramatically in recent years, whereas perinatal mortality rates have fallen. To investigate the hypothesis that these two events are not necessarily causally related, a prospective attempt to modify obstetric management directed at minimizing the rate of abdominal delivery while preserving excellent perinatal survival was done at a university-affiliated hospital in the Denver metropolitan area. Unselected patients who were admitted to separate services at the hospital were used for comparison, with one group subject to the specific management criteria. Corrected mortality rates and low five-minute Apgar scores on the two services were not significantly different after two years. The total cesarean section rate on the first service was 5.7%, and the total cesarean section rate on the comparison service was 17.6%. Analysis of the data showed major differences in indications for cesarean section in the areas of repeat cesarean section, cephalopelvic disproportion, breech presentation, fetal distress, and genital herpes. These data support the contention that excellent perinatal outcome can be achieved with modest abdominal delivery rates. PMID- 4038792 TI - Relationships among premenstrual symptoms and menstrual cycle characteristics. AB - The severity of premenstrual syndrome symptoms has been described by different investigators as varying directly or inversely with the severity of dysmenorrhea. In a large population of women undergoing comprehensive psychological and medical evaluation for premenstrual syndrome complaints, the authors examined the relationship between menstrual cycle parameters and premenstrual syndrome. The severity of premenstrual symptoms varied directly with the severity of dysmenorrhea and premenstrual spotting but was not associated with any other menstrual cycle parameter. Multivariate analysis revealed that social and psychological variables are more strongly associated with variations in premenstrual symptoms than are any menstrual cycle parameters. PMID- 4038793 TI - Rectal serosal hematoma: an unusual complication of culdocentesis. AB - Culdocentesis is currently a widely used diagnostic technique in gynecology. Although associated with numerous theoretical risks, few complications have been documented in anecdotal reports. Rectal serosal hematoma, an unusual complication of culdocentesis, is described. PMID- 4038794 TI - Retinal burns from experimental laser iridotomy. AB - Simulated argon laser iridotomy was performed in 12 cynomolgus monkey eyes to evaluate the effectiveness of the Abraham iridectomy lens in preventing inadvertent retinal burns. At 600 milliwatts, only two of the three eyes developed small retinal burns using the Abraham lens, whereas three eyes developed larger retinal burns without the Abraham lens. At 1000 milliwatts, retinal burns occurred with or without the Abraham lens, but the size and intensity of the burns were reduced with the lens. PMID- 4038795 TI - The histopathology of involutional ectropion. AB - Twenty eyelid specimens from patients with involutional ectropion, obtained by full-thickness horizontal shortening procedures, were examined histopathologically by light and electron microscopy and compared with six normal eyelids from exenteration specimens. Paralytic, cicatricial, and congenital ectropions were excluded from the study. The main histopathologic features included: (1) collagen degeneration and elastosis of the tarsal plate; (2) increased amounts of adipose tissue in the distal tarsus and capsulopalpebral fascia; (3) subacute inflammation and epidermidalization of the tarsal conjunctiva; (4) focal degeneration, fibrosis and elastosis of pretarsal orbicularis, and occasionally minimal change in the muscle of Riolan; and (5) arteriosclerosis of the marginal artery. The combination of these histopathologic changes characterize and may contribute to the development of ectropion of the eyelid associated with aging. PMID- 4038796 TI - Hypotony and ciliochoroidal detachment following pharmacologic aqueous suppressant therapy in previously filtered patients. AB - This is the first report describing the syndrome of hypotony and ciliochoroidal detachment following pharmacologic aqueous suppressant therapy in previously filtered eyes. Four patients had a history of advanced primary open-angle glaucoma treated with multiple medical therapies, including timolol for 11 to 36 months. They then underwent filtration surgery, which failed in two cases. Timolol and/or acetazolamide therapy was instituted 1 to 18 months following surgery. The patients then developed hypotony and ciliochoroidal detachment, which resolved spontaneously after cessation of the pharmacologic aqueous suppressant therapy. In three of the cases, the episode of hypotony and ciliochoroidal detachment recurred after a second challenge with timolol and/or acetazolamide therapy. Inflammation, tumor, wound leakage, retinal detachment and cyclodialysis cleft were excluded. A mechanism of formation of ciliochoroidal detachment in this syndrome is proposed. Long-term timolol therapy followed by filtration surgery and its attendant postoperative hypotony and ciliochoroidal detachment sensitizes the ciliary epithelium. Subsequent pharmacologic aqueous suppressant therapy results in almost total reduction of aqueous production, causing hypotony and ciliochoroidal detachment. PMID- 4038797 TI - [Growth in puberty]. AB - During puberty growth velocity increases within 3 years from a prepubertal nadir to a maximum, in male to 9-10 cm/year, in female to 7-9 cm/year. This spurt is triggered by the androgenic steroids, in male mainly by testicular testosterone. In patients with anorchia the pubertal growth spurt is missing. The androgens have a dual effect. 1. As comes forth from observations in hypopituitary dwarfs being treated with constant replacement doses of hGH, these steroids potentiate the growth-stimulatory effect of hGH. In order to continue growing at all, these dwarfs need the additional medication of androgenic or anabolic steroids if they are hypogonadotrophic. 2. As demonstrated by our measurements of the nocturnal hGH secretion, androgenic steroids enhance the spontaneous production of hGH by a factor of 2-3. Biologically active androgens appear to be a conditio sine qua non for longitudinal growth after age 11-12. This is in concordance with the statement that adult male castrates are no giants as has often been claimed. The rather tall eunuchs in Istanbul were no Turks but as a rule Sudanese negroes who are racially much taller than Turks. PMID- 4038798 TI - Preschool performance of children with normal intelligence who were very low birth-weight infants. AB - Children who were very low-birth-weight infants (less than 1,500 g), beneficiaries of modern neonatal intensive care, are now of school age. To evaluate their school performance 80 children born in 1976 who had very low-birth weight (mean birth weight 1.2 kg, mean gestational age 30 weeks) were examined at age 5 years. Sixty-five children were neurologically intact and had normal IQ (greater than or equal to 85) on the Stanford-Binet; five children were neurologically abnormal and ten had IQ below 85. Of the 65 children with normal intelligence and no neurologic impairments, 46 were single births and enrolled in preschool. These 46 children were matched by race, sex, and family background with classmate control children who had been born at full term. Outcome measurements included the Slosson Intelligence Test, the Woodcock-Johnson Psycho Educational Battery (including subscales of Picture Vocabulary, Spatial Relations, Memory for Sentences, Visual Auditory Learning, Quantitative Concepts, and Blending) and the Beery Developmental Test of Visual-Motor Integration. No significant differences in IQ were found between children who were very low-birth weight infants and control children; however, children who were very low-birth weight infants performed significantly less well on the Spatial Relations subtest of the Woodcock-Johnson and on the Visual-Motor Integration test. Similar results were found for nine sets of twins and their control children. Recognition of these perceptual and visual-motor problems may permit appropriate early remedial intervention and prevent the compounding of these difficulties. PMID- 4038799 TI - [Stenocardia of effort and severe heart rhythm disorders in combined hypertrophic cardiomyopathy and Wolff-Parkinson-White syndrome in childhood]. PMID- 4038800 TI - Low level lead effects on activity under varying stress conditions in the developing rat. AB - The study was designed to determine whether lead ingestion by nursing rats would affect the way offspring reacted to the stress inducing properties of the test environment both as juveniles and mature rats. Dams were exposed to diets with 0.0, 0.2, 0.4 or 1.0 percent by weight metallic lead. Mean blood-lead levels of pups at weaning were 4, 25, 36 and 55 micrograms/100 ml of blood respectively. The stress factor was varied by (1) changing the test apparatus, i.e., forcing rats to occupy an open field or allowing the animal to be a free agent in the start box of a T-maze; (2) testing rats under a longitudinal and a cross sectional experimental design to vary familiarity with the apparatus; and (3) comparing behavior in the presence or absence of noise. Reactivity was assessed by examining the inter-and intra-session pattern of ambulations and defecations. Analysis of data revealed that lead treated rats demonstrated the greater response to stress. This response was generally dose related although recovery was dependent upon the test applied and measures taken. The findings provide a conceptual framework to account for varied results across previous studies. PMID- 4038801 TI - d-Amphetamine induced changes in social interaction patterns. AB - The behavioral effects of d-amphetamine were studied in a group of stumptail macaques in a large outdoor enclosure. d-Amphetamine altered characteristic patterns of aggressive and affiliative behaviors in adult males that received the drug. Each monkey that received d-amphetamine increased its aggression toward non adult animals in the group and decreased aggression toward adult members. In subjects for which genealogy was known, d-amphetamine increased aggression toward kin-related members of the group and decreased aggression toward non-kin monkeys. The effects of the drug on affiliative behaviors were less uniform and, therefore, less conclusive. Three subjects decreased affiliation and two increased affiliation toward non-adult monkeys. The results demonstrate that d amphetamine can alter substantially the behavior of drug-treated members of a group and, in addition, that the drug can indirectly affect specific subsets of the group even though they did not receive the drug. PMID- 4038802 TI - Relationship between initial sensitivity to ethanol and the high alcohol intake in dependent rats. AB - The high spontaneous intake of ethanol, which can be induced in rats after a period of forced administration, may be used to study the altered state created in the C.N.S. by the chronic exposure to ethanol. The relationship between the initial acute sensitivity to ethanol and this induced high oral intake has been examined in rats. Initial sensitivity was determined in two groups of rats either by a test of motor impairment or by alcohol induced hypothermia. After 15 days of daily IG administration of 10 g/kg, rats were submitted to the ethanol presentations which display the high voluntary intake. Two groups of controls were initially tested for their motor impairment or hypothermia respectively under ethanol and then treated for 15 days with saline injections. The results indicate a highly significant negative correlation between initial sensitivity and the level of dependence induced by a chronic treatment and manifested by a voluntary high intake. In control groups, the low intake of ethanol observed in the final test was not correlated to the initial sensitivity to ethanol as tested by hypothermia but weakly correlated to sensitivity measured by motor impairment. The results are discussed in terms of mechanisms which determine the voluntary intake of ethanol in ethanol naive and dependent rats. PMID- 4038803 TI - GABA mediation of the central effects of acute and chronic ethanol in mice. AB - In acute ethanol studies aminooxyacetic acid (AOAA) alone produced marked hypothermia although a test dose of ethanol was able to produce a further drop in body temperature in AOAA treated mice. Even though tolerance to ethanol-induced hypothermia was present in ethanol-dependent mice, AOAA administration was able to produce a further decrease in body temperature. Bicuculline potentiated ethanol-induced hypothermia in the acute studies but the tolerance to hypothermia which had developed in ethanol-dependent mice prevented the bicuculline-induced potentiation of ethanol hypothermia. AOAA markedly potentiated acute ethanol induced motor incoordination whereas bicuculline had no effect. Although partial tolerance had developed to ethanol-induced motor incoordination in dependent mice, AOAA potentiated, whereas a lower dose of bicuculline antagonized, motor incoordination. In the acute studies ethanol had a biphasic effect on AOAA induced GABA accumulation in the hypothalamus and corpus striatum: low doses prevented and a slightly higher dose was without effect on GABA accumulation. Ethanol-dependent mice were unable to respond to an AOAA-induced increase in GABA accumulation although basal levels of GABA were unaffected by chronic ethanol ingestion. The results show that brain GABA or GABA-mediated central mechanisms may be involved in the mediation of ethanol-induced motor incoordination but not hypothermia. PMID- 4038804 TI - Capsular contracture after augmentation mammaplasty. PMID- 4038805 TI - Acute radiation effects on the content and release of plasminogen activator activity in cultured aortic endothelial cells. AB - Confluent monolayers from three lines of bovine aortic endothelial cells were exposed to a single dose of 10 Gy of 60Co gamma rays. Seventy-two hours later, the morphology of the irradiated and sham-irradiated monolayers was examined, and cellular DNA and protein contents were determined. In addition, the release of plasminogen activator (PA) activity into the culture media and PA activity in the cell lysates were assayed. Irradiated monolayers maintained their cobblestone appearance, but individual endothelial cells were enlarged considerably compared to sham-irradiated cells. DNA and protein contents in the irradiated monolayers were reduced to 43-50% and 72-95% of the control levels, respectively. These data indicate that radiation induced cell loss (detachment and/or lysis) from the monolayer, with hypertrophy of surviving (attached) cells to preserve the continuity of the monolayer surface. Total PA activity (lysate plus medium) in the irradiated dishes was reduced to 50-75% of the control level. However, when endothelial PA activity was expressed on the basis of DNA content, the irradiated monolayers from two of the three cell lines contained significantly more PA activity than did sham-irradiated monolayers. Most importantly, the percentage of the total PA activity released into the culture medium by irradiated cells (5 22%) was significantly (P less than 0.001) lower than that released by sham irradiated cells (23-68%). These data suggest that fibrinolytic defects observed in irradiated tissues in situ may be attributable at least in part to a radiation induced inhibition of PA release by vascular endothelial cells. PMID- 4038806 TI - [Therapeutic effect of vegetable oils and ubiquinone-9 on radiation injuries]. AB - The comparison was made of the protective (the administration 3 h before irradiation with a dose of 7.3 Gy) and therapeutic (the administration immediately and later after exposure) effects of soya oil (150 mg/kg) and oil solution of ubiquinone-9 (100-200 mg/kg) on survival of exposed rats. It was shown that soya oil and ubiquinone-9 increased the survival rate of rats when administered before and, to a lesser extent, immediately after irradiation. Corn oil administered immediately after exposure increased the survival rate as well. DMF for the therapeutic effect of soya oil solution of ubiquinone-9 was 1.08. PMID- 4038807 TI - [Characteristics of the descendants of male dogs exposed to chronic combined gamma-irradiation and in the postradiation period]. AB - A study was made of the descendants of 12 male dogs subjected to gamma irradiation during six years at dose-rates of 0.0034 Gy/day and 0.0017 Gy/day + additional annual exposures to gamma-radiation three times a year each of 0.42 Gy. The observations were made during 3 years after the end of irradiation. It was shown that the descendants reflected the regularities of the disorders revealed in fathers' spermatogenesis. The radiobiological effects were function of dose--rate and cumulative radiation dose. The changes were mainly noted during embryogenesis and manifested by the sterility, mortinatality and the decreased number of puppies in the postreity. PMID- 4038808 TI - [Hemangiosarcoma of the liver in workers of the PVC industry and other VC-induced diseases with angiologic-dermatologic, hepatologic, radiologic and neurologic symptoms]. AB - Occupational diseases resulting from exposure to vinyl chloride (VC) include angiosarcoma of the liver and other neoplasms. Among workers exposed to VC we have found capillary abnormalities in the extremities, with scleroderma and Raynaud syndrome, acro-osteolysis, neurological and psychiatric diseases and chromosome abnormalities, as well as abnormal liver metabolism and haematological findings. PMID- 4038809 TI - Magnetic resonance imaging: absence of in vitro cytogenetic damage. AB - Human lymphocytes and Chinese hamster ovary (CHO) cells in culture were exposed for 12 1/2 hours to a magnetic resonance imaging apparatus with a 2.35-Tesla magnet and 100-MHz radio frequency emission. The cells were examined for cytogenetic damage manifested either as chromosome aberrations or sister chromatid exchanges (SCEs), which constitute very sensitive measures of genetic and cellular damage. In either unstimulated or stimulated human lymphocytes, as well as in exponentially growing CHO cells, no increase in either chromosome aberrations or SCEs was found as a result of exposure to these MR conditions. The data indicate that long-term exposure to MR imaging conditions far exceeding those to be found in the clinical situation does not cause cytogenetic damage. PMID- 4038810 TI - [Changes in the conditions of milk extraction as affected by a beta mimetic (isoprenaline) administered by intrajugular route during mechanical milking of cows]. AB - Between days 80 and 105 of lactation, 11 FFPN cows (table 1) received an intrajugular injection of either 0.9% NaCl or 0.3 mg of isoprenaline (IPN = beta receptor agonist). Each of the two treatments was repeated at least 7 times by giving NaCl and IPN on successive, alternate days. IPN: - did not change either the total milk yield of the morning milking (13.5 l vs 13.37 l with NaCl) or the volume of milk obtained by stripping (0.460 l vs 0.447 l with NaCl), although individual responses varied considerably (table 3); - significantly increased milk flow by about 25% because it reached 1.144 l/min/quarter after IPN administration vs 0.929 l/min/quarter after NaCl injection (table 4). These results confirm our previous observations concerning milk loss between milkings (Bernabe and Peeters, 1980), i.e. the stimulation of smooth muscle beta-receptors enhances milk flow. PMID- 4038811 TI - Transmission of a malignant catarrhal fever-like syndrome to sheep: preliminary experiments. AB - The transmission of a malignant catarrhal fever-like syndrome to sheep is reported. Fetal sheep between 40 and 66 days gestation were inoculated intravenously with viable cells either from a red deer with clinical malignant catarrhal fever or from rabbits with the disease. Of the 21 fetuses in the experiment only five were born live and of these four developed clinical signs similar to malignant catarrhal fever in other species and died or were killed 10, 16, 47 and 175 days after birth. The fifth lamb remained unaffected. Histology of the four affected lambs revealed a generalised lymphoproliferation, with T dependent areas of lymphoid tissues being affected, and an overall paucity of immunoglobulin containing cells. In addition arteritis and interstitial infiltration of many organs by lymphoid cells was present. The infectious agent was not reisolated in rabbits from lambs or passed to red deer housed in the same pen and it is thus considered possible that gene expression of the putative virus was incomplete. PMID- 4038812 TI - [Injuries of the urinary tract]. PMID- 4038813 TI - Sex hormone-binding globulin--still many questions. PMID- 4038814 TI - The kinetics of short-lived indium-111 radiolabelled platelets. AB - We have studied the kinetics of autologous 111In-labelled platelets in patients with reduced platelet life span (less than 4.5 d), most of whom were thrombocytopenic, and of homologous 111In-labelled platelets in patients with severe thrombocytopenia. Intrasplenic platelet transit time (t) was calculated by compartmental and deconvolution analysis. In patients with a mean platelet life span of less than a few h, compartmental analysis may not be valid and so only deconvolution analysis was applied. There was a close correlation between values of t given by the two approaches (r = 0.88, n = 18, P less than 0.001). In some patients with severely reduced mean platelet life span (MPLS), the deconvolved splenic platelet clearance curves appeared to approach an asymptote, the relative magnitude of which was indicative of the irreversible extraction fraction by the spleen of incoming platelets. In other patients with severely reduced MPLS resulting from abnormal intra-hepatic platelet destruction, the deconvolved splenic curves resembled the normal. The intrasplenic platelet transit time showed no clear relationship with other parameters. It was concluded that platelet pooling within the spleen is normal in patients with reduced platelet life span, including idiopathic thrombocytopenic purpura, even when the predominant site of destruction is the spleen, and that platelets are not delayed in transit through the spleen in preparation for their removal from the circulation and ultimate destruction. PMID- 4038815 TI - How many plasma exchanges to cure thrombotic thrombocytopenic purpura? AB - 7 patients were treated by plasma exchanges and antiplatelet drugs for thrombotic thrombocytopenic purpura (TTP). The effectiveness of therapy was reviewed daily and retrospectively estimated on day 3, d6, d9, and d12. 6 of these 7 patients were cured. The low predictive value of the initial response to therapy is underlined. The clinical and biological status on d12 seems to have the best predictive value for the final outcome. These data encourage us to continue the plasma exchanges until d12, whatever the initial response to therapy in TTP. PMID- 4038816 TI - [Destruction of helminth eggs in sewage sludge purification plants]. PMID- 4038817 TI - Direct visualization of organelle movement along actin filaments dissociated from characean algae. AB - A system has been developed in which organelle transport can be studied without the influence of an organized cellular cytoplasm. Binding and continuous unidirectional movement of organelles along isolated cellular transport cables were directly visualized by video light microscopy after the dissociation of the cytoplasm of characean algae cells in a Ca2+-free buffer containing adenosine triphosphate. Individual organelles had more than one attachment site and moved at mean rates of 11.2 or 62.1 micrometers per second along multiple parallel pathways on each cable. Electron microscopy of these cables after direct freezing demonstrated that they consist of compact bundles of actin filaments. Under these conditions, characteristics of organelle movement should reflect directly the underlying molecular processes of binding and force generation. PMID- 4038818 TI - Disorganization of cultured vascular endothelial cell monolayers by fibrinogen fragment D. AB - Fibrinogen fragment D, which is heterogeneous, has several important biological functions. Human fibrinogen fragments D94 (molecular weight, 94,000), D78 (78,000), and E (52,000) were purified. Fragments D78 and D94 but not purified fibrinogen or fragment E specifically caused disorganization of bovine aortic endothelial cells cultured as monolayers. Within 2 hours of exposure to pathophysiological concentrations of fragment D, the confluent endothelial cells retracted from each other and projected pseudopodia. These disturbed cells subsequently became rounded and detached from the substrate. The actin present in stress fibers in stationary monolayer cells was diffusely redistributed in cells with fragment D-induced alterations in morphology. This effect was not observed in monolayers of kidney epithelial cells. The results demonstrate a specific effect of fibrinogen fragment D on the disorganization of cultured vascular endothelial cell monolayers and suggest that fragment D plays a role in the pathogenesis of syndromes with vascular endothelial damage. PMID- 4038819 TI - Cisplatin, etoposide, and radiotherapy in regional inoperable squamous cell carcinoma of the bronchus. AB - Thirty-three ambulatory patients with limited stage, inoperable, squamous cell carcinoma of the bronchus were administered cisplatin (60 mg/m2 IV on day 1) and etoposide (VP-16) (400 mg/m2 orally in divided doses over days 3, 4, and 5). This regimen was repeated every 28 days for a maximum of six courses. Radiotherapy was given to patients who did not respond to chemotherapy for urgent relief of local symptoms, or as adjuvant to chemotherapy in responding patients. Response to chemotherapy was assessable in 28 patients. Patients experiencing early death were included in the evaluation. Ten patients (36%) had progressive disease and nine (32%) had stable disease during chemotherapy. Eight patients achieved radiologically verified partial response (PR) and one, a complete response (CR) verified bronchoscopically, yielding an overall response rate of 32%. Of responding patients who proceeded to radiotherapy, one patient showing PR was converted to a CR; another patient with PR improved, although not to CR. The median survival of 33 patients was 49 weeks. There were two deaths among nine responding patients (at 38 and 48 weeks), and nine deaths among 19 nonresponders (six before the 27th week). The principle toxic reactions were nausea and vomiting, which were serious (greater than grade 2) in 29 of 33 patients. All patients receiving more than one course of chemotherapy suffered total alopecia. Cisplatin/etoposide is an effective combination in some patients with regional, squamous cell lung cancer, but randomized trials comparing it to radiotherapy alone are required to establish real survival benefit. PMID- 4038820 TI - VP-16 and cisplatin in the treatment of non-small-cell lung cancer. AB - The EORTC Lung Cancer Working Party investigated the effects of combination therapy with VP-16 (Ve-Pesid) and cisplatin in the treatment of non-small-cell lung cancer (NSCLC). Neither agent alone is recognized as being associated with a high rate of response in NSCLC, but the combination proved beneficial in our hands and effected a total response rate (including complete and partial responses) of over 40%. In addition to this encouraging result, complete remissions occurred in a modest number of patients. The addition of vindesine to the regimen profferred no benefit, but did increase the incidence of toxic reactions. Preliminary data on supraconventional dosages of cisplatin indicate a trend toward better response and longer survival but a significantly higher frequency of severe leukopenia as well. No studies have yet been conducted with higher doses of VP-16 in NSCLC patients, but related investigations into the treatment of small-cell bronchogenic carcinoma indicated that doses up to 3 g/m2 of VP-16 were well tolerated by patients. It is cautiously concluded that the combination of cisplatin and VP-16 probably offers an advantage over single-drug therapy with either agent alone in the treatment of non-small-cell lung cancer. PMID- 4038821 TI - Metronidazole and trichomoniasis. PMID- 4038822 TI - The role of luminal pH in production of gastrin cell hyperplasia in the rat. AB - Truncal vagotomy is associated with diminished gastric acid production, gastrin cell hyperplasia, and elevated serum gastrin levels. To study the role of reduced antral luminal acidity in the production of gastrin cell proliferation, gastrin cell densities were quantitated in preparations involving exposure of the antral mucosa to a non-acid lumen at different levels of the gastrointestinal tract. Female Sprague-Dawley rats were divided into the following experimental groups: intact controls, shams, antral diverticulum on the jejunum, antral diverticulum on the ileum, and antral diverticulum on the colon. At death, 2 weeks, 2 months, and 6 months after operation, luminal pH was at least 5.8 for each group of rats with antral diverticula. No significant changes in gastrin cell numbers were observed in rats with jejunal or ileal diverticula. For those animals with colonic diverticula, gastrin cell counts were increased 55% at 2 weeks (503 +/- 23 cells per cm versus 320 +/- 13 cells per cm for shams). At 2 months gastrin cell numbers had increased further (639 +/- 54 cells per cm) in rats with antral diverticula on the colon. Gastrin cell proliferation was sustained at 6 months in this group. A factor other than reduced luminal acidity induces gastrin cell proliferation in antral mucosa exposed to colonic content. The responsible agent is not present in the small-bowel lumen. A non-acid luminal environment is not, by itself, a sufficient stimulus for gastrin cell hyperplasia. PMID- 4038823 TI - Factors influencing the development of serum precipitins to farmer's lung antigen in Quebec dairy farmers. AB - A total of 888 randomly selected dairy farmers participated in an epidemiological study to evaluate the prevalence of precipitins to farmer's lung antigens, and the socioeconomic factors associated with their presence. Precipitins were present in 75 farmers (8.4%) (65 to Micropolyspora faeni, seven to Aspergillus spp, two to both Aspergillus and Micropolyspora faeni, and one to Aspergillus and Thermoactinomyces vulgaris). The titres ranged from a dilution of 1/32 to a concentration of X 2 (Ouchterlony's double diffusion method). In the study population there were 544 who had never smoked, 146 ex-smokers, and 198 smokers. Sixty nine precipitin positive subjects were either never smokers or ex-smokers; only six were smokers. The negative relationship between cigarette smoking and precipitins was highly significant (p = 0.004). Factors positively associated with positive precipitin reactions were: size of farm, time spent in the barn, and the presence of a family member previously diagnosed as having farmer's lung disease. Interestingly, positive precipitin reactions were not associated with any of the following: use of silos, hay conditioners, or hay dryers; the presence or quantity of mouldy hay; or the presence of respiratory symptoms. It is concluded that precipitin analysis is not useful as a screening method for farmer's lung, though it can be of diagnostic value in acute farmer's lung disease. PMID- 4038824 TI - Effect of specific thromboxane-synthetase inhibition on thromboxane and prostaglandin synthesis in stable angina induced by exercise test. AB - 14 patients with effort induced angina pectoris were treated with a specific TxB2 inhibitor Dazoxiben or verapamil for two weeks with a wash-out period of 14 days between the two regimens. A sub-maximal bicycle test was performed before treatment and at the end of each treatment period. The bicycle test induced a significant increase in serum TxB2 in patients without treatment and during verapamil therapy. This increase was significantly inhibited by Dazoxiben treatment. No alterations in plasma TxB2 or 6-keto-PGF1 alpha were observed on either regimen. Dazoxiben had no clinical effect, while verapamil caused a highly significant prolongation of exercise time. PMID- 4038825 TI - [Cisplatin drug therapy. Antiemetic treatment. Experiences with the use of high dose metoclopramide combined with chlopromazine and prochlorperazine]. PMID- 4038826 TI - Chronic low-lead exposure from birth produces deficits in discrimination reversal in monkeys. AB - Cynomolgus monkeys (Macaca fascicularis) were dosed from birth with 100, 50, or 0 micrograms/kg/day of lead. This protocol resulted in blood lead concentrations of 25, 15, or 3 micrograms/dl, respectively, before withdrawal of infant formula at 200 days of age. Blood lead concentration declined thereafter over the next 100 to 150 days to steady-state levels of 13, 11, or 3 micrograms/dl. At approximately 3 years of age, monkeys were tested on a series of three discrimination reversal tasks: nonspatial form discrimination, nonspatial color discrimination with irrelevant form cues, and nonspatial form discrimination with irrelevant color cues. The higher dose group was impaired relative to controls over the entire experiment (all three tasks combined), the two form discrimination tasks combined, and the form discrimination with no irrelevant cues. Deficits were most marked over the first several reversals. The lower dose group was impaired on the color discrimination task and on the last several reversals of all tasks combined. In addition, the higher dose group was impaired relative to the lower dose group over the entire experiment. PMID- 4038827 TI - [Deaths due to suicide and accidents in relation to menstrual cycle]. PMID- 4038828 TI - Retention of urine in genital herpetic infection. Survey and case report. AB - During the last years several cases of acute urinary retention, due to genital herpetic infection, have been described, especially in youngsters. The condition is caused by neurogenic dysfunction due to a sacral meningomyelitis. The clinical picture before the acute attack is characterized by painful genital eruptions; fever and malaise; tender inguinal lymph nodes; paresthesia in the perineum and on the inside of the thigh, and obstipation. Skin and mucous membrane manifestations are often sparse or located so that they are easily overlooked. The treatment is bladder drainage until the patient is able to void spontaneously. Most of the patients regain normal bladder function within 10 days, but bladder dysfunction for 5 weeks has been described. We present a typical case of acute urinary retention due to genital herpetic infection. PMID- 4038829 TI - Sexual and marital relationships after treatment for nonseminomatous testicular cancer. AB - Data from 121 patient questionnaires suggest that treatment for nonseminomatous testicular cancer not only causes sterility but also disrupts marital and sexual happiness in 10 to 20 per cent of patients. Treatment included unilateral orchiectomy and retroperitoneal lymphadenectomy alone in 47 men; 30 had additional chemotherapy, 8 had additional radiotherapy, and 26 were treated with all three modalities. Erectile and orgasmic problems were more prevalent when radiotherapy was included. Compared with healthy men, patients reported less sexual activity, lower sexual desire, more erectile dysfunction, more difficulty achieving orgasm, reduced orgasmic intensity, and, for 82 per cent, a greatly reduced semen volume. The longer the time since treatment, the more likely the patient was to have antegrade ejaculation. Although the patients' 12.8 per cent divorce and/or separation rate is not unusually high, those whose marriages ended cited sexual dysfunction and cancer treatment as significant sources of stress. Sterility was a frequent source of anxiety for one quarter of the patients. PMID- 4038830 TI - Priapism. PMID- 4038831 TI - Treatment of gid. PMID- 4038832 TI - Index Lists provided by the VAMPP computer programme for dairy herd health and production control. II. Interpretation and analysis of data on Index List 2. AB - In a series of four papers computerized herd reports on various aspects of dairy farming, the Index Lists, are presented for herd health and production control purposes. This second paper presents Index List 2, on calving, breeding efficiency and lameness. The information from this list is suitable to monitor herd performance, especially when used in combination with information from other index lists. Methods for interpretation and evaluation of the data listed are provided. Evaluations should take those aspects related to reproduction and lameness into account. The use of current information and prompt computerized analysis in detecting deviations in index figures and providing advice to farm management is discussed. PMID- 4038833 TI - C6-deficiency in rabbit serum and its restoration by normal rabbit serum or by normal bovine serum. AB - The sera from 12 out of 29 half-sibs of the New Zealand White breed of rabbit were inactive, when used as complement, in blood-typing tests of bovine erythrocytes. This defect was found to be due to a deficiency in the activity of the component C6. A dilution of 1:380 of pooled normal rabbit sera and a dilution of 1:520 of pooled normal bovine sera were capable of restoring, to 63%, the haemolytic capacity of the defective rabbit sera. The rate of haemolysis varied from 4% to 100% when the defective sera were restored by sera from different sets of monozygous bovine twins. PMID- 4038834 TI - [Angiosarcoma in newborn infants (case report)]. PMID- 4038835 TI - Characterization of fibrinolytic activity in human vascular grafts. PMID- 4038836 TI - [Metabolic mechanisms of long-term effects of environmental chemical factors- carcinogenic, embryotoxic, gonadotoxic, mutagenic and gerontologic effects]. PMID- 4038837 TI - [Epidemiology of fatal abnormalities in Switzerland]. AB - Official certificates of stillbirth and infant death are analysed in the birth cohort of 1979-81. Congenital malformations account for approx. 40% of infant mortality. Cantonal differences in malformation rates are not explained by different incidence of such malformations only, but also by differences in lethality. Incidence of Anencephaly is examined in detail. PMID- 4038838 TI - Glial filaments are a major brain fraction in infantile neuronal ceroid lipofuscinosis. AB - Extremely severe gliosis develops at the end stage of infantile neuronal ceroid lipofuscinosis (INCL), a fatal encephalopathy characterized by accumulation of autofluorescent storage material in the brain and other tissues followed by a terminal subtotal neuronal and myelin loss. A major fraction of highly enriched intermediate filaments was obtained with a density gradient centrifugation method from INCL brain tissue, whereas the storage material represented only a minor fraction. SDS-polyacrylamide gel electrophoresis of the filament fraction showed a major protein with molecular weight of 51 kD and three to four polypeptides of 40-48 kD identified as glial fibrillary acidic protein (GFAP) and its degradation products by the immunoblotting technique with monoclonal antibodies against GFAP. Immunization experiments with the isolated INCL glial filament fraction produced antibodies reacting only with GFAP but not with other types of intermediate filament proteins, furthermore indicating a high content of GFAP in the isolated fraction. No significant amounts of vimentin or other types of intermediate filament proteins could be detected. These results document the extremely high content of glial filaments at the terminal stage of INCL and suggest that INCL brain may serve as a good human model for studies on the composition of glial filaments in vivo and on the pathogenesis of gliosis. PMID- 4038839 TI - Axonal and myelin lesions in beta-mannosidosis: ultrastructural characteristics. AB - Ultrastructural changes in central nervous system (CNS) white matter of three goats affected with beta-mannosidosis were analyzed to further define characteristics and pathogenesis of axonal and myelin abnormalities. The variations in myelin association and contents of axonal spheroids were delineated. The occurrence of spheroids in a 96/150-day fetus documented the early development of these axonal lesions. In regions of severe myelin deficits, the presence of apparently normal axons and a reduction in the number of oligodendrocytes were confirmed. Many remaining cells in myelin-deficient regions were characterized by dark, vacuolated cytoplasm. The occurrence of internodes with myelin sheaths adjacent to internodes without myelin sheaths suggested that an axonal defect is not primarily responsible for the absence of myelin sheaths. A mild myelin deficit in the spinal cord was indicated by the presence of unmyelinated axons. Except for occasional mild cytoplasmic vacuolation, the spinal cord glial cells appeared relatively normal. The findings presented here are consistent with the hypothesis that an oligodendrocyte defect, expressed by regional differences, is a major factor in the pathogenesis of myelin deficiency in beta-mannosidosis. PMID- 4038840 TI - Treatment of advanced endometrial carcinoma with cisplatin, cyclophosphamide and doxorubicin. AB - A patient with advanced adenocarcinoma of the endometrium was treated with cisplatin, cyclophosphamide and doxorubicin. This regimen achieved surgically proved complete remission. No severe drug-related toxicity occurred. PMID- 4038841 TI - Haemangioblastoma of the brain. Computed tomography and angiographic studies in 17 patients. AB - Between 1975 and 1983, 17 patients who underwent surgery for haemangioblastomas of the brain (16 lesions occurring in the posterior fossa) were studied with CT scans (17 cases) and vertebral angiograms (15 cases). The CT scans were superior for demonstrating a cystic tumour, its topography in the posterior fossa, its relationship to the fourth ventricle, and the presence and degree of an obstructive hydrocephalus. The vertebral angiographies were more sensitive and specific than CT for revealing the vascular nature, and were imperative in order to establish the supply and drainage of the tumours. It is clear that CT and angiography each make an important contribution toward defining these tumours. Their association is necessary. PMID- 4038842 TI - Asymmetric septal hypertrophy and sympathetic overactivity in normotensive hemodialyzed patients. AB - Sympathetic activity has been evaluated in 23 chronic uremic normotensive patients on long-term hemodialysis. M-mode and bidimensional echocardiographic finding of asymmetric septal hypertrophy (ASH) was shown in seven (30.4%). Sympathetic function was assessed by determining arterial plasma norepinephrine (plasma NE) and epinephrine (plasma E) in supine and upright positions, both before and after dialysis. After dialysis standing caused a significant increase in plasma NE levels in the patients with ASH in comparison to the patients without ASH and the control group. A significant decrease in mean blood pressure (mBP) and a sharp heart rate (HR) increase were detected in the patients without ASH, whereas mBP and HR were unchanged in the patients with ASH. Predialysis serum creatinine and fasting triglycerides were found to be significantly higher in the group with ASH. These results suggest that sympathetic overactivity may play a role in the development of interventricular septum hypertrophy. This increased neurosympathetic responsiveness is probably related to the counteraction of the postural dialysis-induced hypotension. PMID- 4038843 TI - Angiosarcoma of the heart. PMID- 4038844 TI - Otitis media and language performance in a cohort of Apache Indian children. AB - Language performance was evaluated in 167 healthy Apache Indian children aged 6 to 8 years, who had contrasting histories of otitis media and who had been followed since birth. All children received pneumatic otoscopy, tympanometry, pure tone audiometry, and a battery of language measures. Groups were similar with respect to age, sex, school experience, family income, housing, primary language spoken, and nonverbal intelligence. No statistically or clinically significant differences in language performance were observed between groups of children with frequent episodes of otitis media and those from the same cohort with infrequent otitis. While frequent otitis media was associated with abnormalities on tympanometry and otoscopy, bilateral hearing loss (greater than 25 dB) was observed in only 1% of the children. PMID- 4038845 TI - Autoimmune thrombocytopenic purpura in the course of Kaposi's sarcoma--report of a case. AB - Autoimmune thrombocytopenic purpura associated with Kaposi's sarcoma in a 42-year old male from the south of Saudi Arabia is reported. This association has not previously been reported in the medical literature. The occurrence of Kaposi's sarcoma in renal transplant recipients and in those suffering from acquired immune deficiency syndrome has been well documented. Kaposi's sarcoma has been infrequently reported in association with autoimmune disorders. The diagnosis of autoimmune thrombocytopenic purpura was made after all secondary causes of thrombocytopenic purpura has been excluded. The diagnosis of Kaposi's sarcoma was confirmed by the histopathological examination of a skin biopsy. To the best of our knowledge, this is the first report of such an association. PMID- 4038846 TI - High-dose intravenous IgG in the management of pregnancy in women with idiopathic thrombocytopenic purpura. AB - Idiopathic thrombocytopenic purpura (ITP) may develop during pregnancy or affect later pregnancies, causing serious risks of bleeding to the mother and fetus. High-dose intravenous immunoglobulin (IGIV) has caused an immediate and predictable rise in platelet count during the infusion in both adults and children with chronic or acute ITP. The rapid rise in platelet counts may be important in preparing pregnant women with ITP for surgery or delivery. We report our experience in managing two women at weeks 29 and 37 week of gestation who required splenectomy and/or cesarean section. Both patients demonstrated an increase in platelet counts, underwent surgery without excess bleeding, and had normal infants with normal platelets, and with mild thrombocytopenia at delivery. PMID- 4038847 TI - Successful management of thrombocytopenia, microangiopathic anemia, and acute renal failure by plasmapheresis. AB - We report on the outcome of six consecutive adult patients who presented with microangiopathic anemia and thrombocytopenia. Clinical parameters on admission included platelet counts less than 45,000/mm3, microangiopathic red blood cell morphology, mental status abnormalities, and in three, rapidly progressive azotemia requiring dialysis. All patients underwent plasma exchange therapy as part of their treatments. Patients with renal failure underwent plasma exchange with a hollow fiber plasma separator, while those without renal failure were treated with a cytocentrifuge. All received fresh frozen plasma as replacement solution and were treated with glucocorticoids as well. For all six patients, plasmapheresis and conventional drug therapy resulted in remission that has lasted for 16 +/- 5 months (range 8 to 24 months). Early cessation of plasmapheresis in two patients resulted in rapid relapse. Patients who required dialysis now have a mean creatinine of 2.0 +/- 0.9 mg/dL (range 1.2 to 3.5). With similar volumes of exchange, and the same number of treatments, less fresh frozen plasma was used in the three patients treated with the hollow fiber separator than in patients treated with the cytocentrifuge (6.3 +/- 3.7 v 14.8 +/- 4.3 U/exchange, P less than 0.05). We conclude that plasmapheresis is a useful therapeutic modality for the treatment of thrombocytopenia and microangiopathic hemolytic anemia. In addition the use of a hollow fiber plasma separator for plasmapheresis is safe and efficient, particularly when concurrent dialysis is required. PMID- 4038848 TI - Twin concordance for a binary trait. II. Nested analysis of ever-smoking and ex smoking traits and unnested analysis of a "committed-smoking" trait. AB - Twin concordance rates for a binary trait can provide information about causes of trait variation. However, if trait prevalence varies with age (or birth cohort) or between the sexes, trait concordance rates will be artificially inflated because of the matching within pairs of twins. Our previous paper showed how to minimize the effects of such confounding by using logistic regression to model trait prevalence as a function of age and sex and that the binary correlation coefficient was useful as a measure of concordance that can be adjusted for trait prevalence. This method is extended here to allow for nested analyses and is applied to the smoking habits of a sample of 3,807 pairs of adult twins. For monozygotic (MZ) twins, the correlation coefficients for the binary trait of "ever-smoking" (males: .50 +/- .04; females: .60 +/- .02) were significantly greater than for dizygotic (DZ) twins (males: .37 +/- .05; females: .31 +/- .04; unlike-sex pairs: .21 +/- .03). For "giving-up smoking," given that both twins were previously smokers, the correlations for MZ twins (males: .37 +/- .07; females: .29 +/- .05) were also greater than for DZ twins (males: .11 +/- .09; females: .26 +/- .08; unlike-sex pairs: .13 +/- .06), although the difference was not statistically significant for females. Current smokers who had been smoking for at least 10 years were arbitrarily defined as "committed-smokers." The binary trait of "committed-smoking" was more strongly correlated in MZ twins (males: .41 +/- .06; females: .41 +/- .04) than in DZ twins (males: .22 +/- .08; females: .18 +/- .05; unlike-sex pairs: .16 +/- .05). These observations suggest that as well as depending on socially determined environmental factors, smoking behavior is influenced by genetic factors and/or by environmental factors unique to the MZ twin environment, which are of particular importance as determinants of "committed-smoking." There is a need for further research to investigate the personal characteristics of "committed-smokers" and to seek intervention strategies that are more suited to the needs of individual smokers. PMID- 4038849 TI - Genes controlling gp25/30 cell-surface molecules map to chromosomes X and Y and escape X-inactivation. AB - The monoclonal antibody AbO13 defines a cell-surface antigen that is expressed on most cultured human cells, but not on rodent cells. AbO13 precipitates glycoproteins of 25,000 and 30,000 mol. wt. from lysates of [3H]glucosamine labeled human cells. Results of the serological typing of a panel of 25 rodent human somatic cell hybrid clones show that reactivity with AbO13 segregates with the human X and Y chromosomes. The presence of either of these chromosomes is sufficient for O13 expression on the hybrid cell surface. Analysis of hybrid clones containing human X chromosomes with karyotypically defined deletions permitted the regional assignment of the X-linked gene locus controlling the expression of O13 to Xp22-pter. In addition, AbO13 is reactive with Chinese hamster-human hybrids derived from fibroblasts of a 49,XXXXX individual that contained only inactivated copies of the human X chromosome. These results suggest that the X-linked locus determining the expression of O13 is not subject to X-inactivation. PMID- 4038850 TI - Use of calcium channel blockers in hypertrophic cardiomyopathy. AB - Recent studies in patients with either obstructive or nonobstructive hypertrophic cardiomyopathy have suggested that increased resistance to diastolic filling of the stiff left ventricle may be an important mechanism contributing to symptoms. These observations have led to exploration of the effects of calcium channel blockers on systolic and diastolic function in patients with hypertrophic cardiomyopathy. Acute hemodynamic studies using verapamil and nifedipine have shown that these agents tend to cause: (1) a slight fall in systemic arterial pressure and reflex increase in heart rate; (2) a reduction in left ventricular outflow gradient in most but not all patients; and (3) variable effect on left side heart filling pressures. In contrast to beta-adrenergic blockers, these hemodynamic effects are not associated with depression of systolic function, but appear to be related to improved left ventricular distensibility. Clinical trials have suggested that long-term administration of verapamil in patients with hypertrophic cardiomyopathy promotes improvement in symptomatic status and exercise tolerance in many but not all patients; similar results have been reported in preliminary studies using nifedipine. Potential major adverse effects include depression of sinoatrial activity and atrioventricular conduction with verapamil, and marked hypotension and, rarely, pulmonary edema with both verapamil and nifedipine. PMID- 4038851 TI - Male-to-male transmission of the hypertelorism-hypospadias (BBB) syndrome. AB - A boy and his father with the hypertelorism-hypospadias (BBB) syndrome are described. This example of male-to-male transmission is evidence that the BBB syndrome is not due to an X-linked gene. PMID- 4038852 TI - Precipitated opiate abstinence in utero. AB - Following direct infusion of morphine (0.6 to 80.0 mg/hr) to the fetal lamb for 2 to 6 hours, naloxone administration precipitated a fetal abstinence syndrome consisting of desynchronization of electrocortical activity; increased total body movements, neck tone, and eye movements; continuous rapid, deep breathing movements; immediate bradycardia associated with transient increases in systolic, diastolic, and pulse pressures; and meconium staining of the amniotic fluid. This syndrome resembles that observed in the opiate-abstinent human neonate. PMID- 4038853 TI - Effect of dexamethasone treatment on sex steroid-binding protein, corticosteroid binding globulin, and steroid hormones in cycling rhesus macaques. AB - We tested the hypothesis that dexamethasone lowers sex steroid-binding protein levels and observed the effect of dexamethasone on corticosteroid-binding globulin and specific steroid hormones in plasma. Four cycling rhesus macaques were studied during three consecutive menstrual cycles (first and third cycles served as controls). In the second cycle, each animal received 0.5 mg of dexamethasone intramuscularly at 8:00 AM and 8:00 PM daily for 21 consecutive days. Blood samples were taken at 1- to 3-day intervals during each cycle. Concentrations of sex steroid-binding protein, corticosteroid-binding globulin, cortisol, testosterone, progesterone, and estradiol were measured in plasma. The percentage and plasma concentration of free testosterone were also determined. Within 2 days of treatment, dexamethasone suppressed cortisol to 5% of baseline values, which returned in the third cycle. All cycles were ovulatory. Dexamethasone significantly lowered plasma levels of all the compounds except progesterone: sex steroid-binding protein, -30%; corticosteroid-binding globulin, -14%; testosterone, -36%; and estradiol, -45%. The percentage of free testosterone was significantly elevated, but free testosterone concentrations were unchanged. Although our data conclusively show that dexamethasone suppresses plasma sex steroid-binding protein levels in the rhesus macaque, it remains to be established whether this suppressive effect leads to an increase in the metabolic clearance rate of testosterone. PMID- 4038855 TI - Treatment of diabetic traction retinal detachment with the pulsed neodymium-YAG laser. AB - Three patients with diabetic traction retinal detachment not involving the central macula were treated with the pulsed neodymium-YAG laser. In each case, with energy levels of 9 to 11 mJ, vitreous traction bands were sectioned and the traction retinal detachment diminished or disappeared. Other than a small choroidal hemorrhage in one instance, no adverse side effects occurred. The pulsed neodymium-YAG laser may provide a new therapeutic modality in a few selected cases of diabetic traction retinal detachment. PMID- 4038854 TI - Recurrent abortions, thromboses, and a circulating anticoagulant. AB - A syndrome occurring recently in young women and consisting of recurrent abortions, thromboses, and a circulating anticoagulant is described. It is suggested that an antiphospholipid antibody may be responsible for this clinical complex. PMID- 4038856 TI - Effect of conceptus number, hysterectomy, and progesterone on prolactin surges in rats. AB - Mating induces two daily surges of prolactin (PRL) secretion in the rat. Termination of the diurnal and nocturnal surges coincides with the development of the placenta and the secretion of rat placental lactogen (RPL). The number of conceptuses present was altered to induce changes in RPL levels in the blood. The presence of one intact viable conceptus is sufficient to cause termination of the diurnal PRL surge. The presence of one or zero conceptuses allowed resumption of the nocturnal surge after day 14, whereas presence of two or more conceptuses prevented the surge. Hysterectomy on day 14 allowed the resumption of the nocturnal PRL surges for 2 days and diurnal PRL surges for 3 days. Progesterone treatment stimulated an additional third nocturnal PRL surge and blunted the magnitude of the resuming diurnal surges. It is concluded that secretions from the conceptus and progesterone contribute to the regulation of prolactin during pregnancy. PMID- 4038857 TI - Frequency modulation and synchronization of spontaneous oscillations in cardiac cells. AB - Both intact mammalian cardiac muscle and single adult Ca2+-tolerant myocytes, under appropriate experimental conditions, exhibit periodic, spontaneous myofilament oscillations that originate locally within a cell and propagate longitudinally as contractile waves. We have used microscopic imaging techniques to study the effect of electrical stimulation on the oscillation characteristics in single rat and rabbit myocytes. Unstimulated rat cells bathed in Cao of 1-3 mM exhibited these oscillations. During stimulation at rates between 6 and 120 min 1, oscillations did not occur in the interval between stimulated contractions, and following termination of stimulation a transient suppression of the spontaneous oscillation frequency occurred. Conversely, with higher cell Ca2+ loading, achieved by increasing the [Ca2+]o or by addition of isoproterenol or ouabain, stimulation caused de novo oscillations in rabbit cells and increased the spontaneous oscillation frequency in rat cells to levels that resulted in their appearance between stimulated contractions. The tendency for myofilament motion to occur simultaneously at multiple foci was also increased by stimulation at high frequencies, and partial synchronization of these foci resulted in oscillations of an increased amplitude. The modulation of the spontaneous oscillation characteristics in single cells by stimulation may explain, in part, some effects of stimulation on Ca2+-dependent oscillatory phenomena in intact cardiac tissues. PMID- 4038858 TI - Statistical significance tests for autoradiographic data. AB - The purpose of this paper is to develop statistical methods that take radiation spread into account in analyzing data from different autoradiographic experiments. The method uses the probability circle analysis of Salpeter and McHenry (1973) to obtain the probable source of each radioactive emission and the circle and point counting method of Williams (1969) to estimate the relative area occupied by each cellular site. Two levels of analysis are presented. The first level of analysis is concerned with estimating relative activities and standard errors for cellular items that are larger than the probability circle. The second level of analysis involves estimating relative activities and standard errors for cellular sites that are smaller than the probability circle and are therefore observed in circles containing another item such as cytoplasmic matrix. Two different tests of hypotheses are discussed. The first null hypothesis is that the radioactivity is randomly distributed among the cellular sites. The second null hypothesis is that there is no difference between two different treatments in the relative activities for a given site. PMID- 4038859 TI - Inhibition and stimulation of enflurane metabolism in the rat following a single dose or chronic administration of ethanol. AB - The effects of a single oral dose or chronic ingestion of ethanol on in vivo and in vitro metabolism of enflurane were studied in Fischer 344 rats. At various intervals after ethanol treatment, enflurane was administered ip and 1 h after enflurane administration fluoride and ethanol levels were measured in plasma and hepatic microsomes were prepared. The concentration of ethanol in plasma (+/- SE) was 0.138 +/- 0.035% at 9 h after the single dose of ethanol and decreased almost to control levels by 17 h. The hepatic microsomal defluorination of enflurane was enhanced 3.5-fold and 6.3-fold at 9 and 25 h after the ethanol dose and returned to the control level by 33 h. In vivo defluorination was inhibited almost completely at 8 h after the ethanol dose, increased to 3.4 times the control level at 24 h, and decreased to the control level by 32 h. At 1 h after the end of chronic ethanol treatment, the concentration of ethanol in plasma was 0.254 +/ 0.018%, and it decreased to the control level by 9 h. Hepatic microsomal enflurane defluorinating activity was increased 10.5-fold at 1 h after the end of chronic treatment and decreased to the control level by 13 h. Immediately following chronic treatment, enflurane defluorination in vivo was almost totally inhibited. It increased to 9.3 times the control level at 4 h after chronic treatment was stopped and then decreased to nearly the control level at 12 h.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4038860 TI - Blastocystis hominis infection presenting as recurrent diarrhea. PMID- 4038861 TI - Platelet-aggregating factor in thrombotic thrombocytopenic purpura. PMID- 4038862 TI - Black galactorrhea as a consequence of minocycline and phenothiazine therapy. PMID- 4038863 TI - Medical management of genital herpes. Advances in antiviral treatment. PMID- 4038864 TI - Recurrent genital herpes simplex infection. A trivial disorder. PMID- 4038865 TI - Angiosarcoma of the face. PMID- 4038866 TI - Identification of sensory neural hearing loss in very preterm infants by brainstem auditory evoked potentials. AB - Brainstem auditory evoked potentials were recorded in 117 newborn infants of less than 33 weeks of gestation. The potentials were absent in 10 infants (bilaterally in eight and unilaterally in two) and present in 107. By 1 year of age nine of the 10 infants with absent brainstem auditory evoked potentials were shown to have sensory neural hearing loss and required hearing aids: the remaining infant had secretory otitis media. None of the 107 infants whose auditory evoked potentials were present were found to have sensory neural hearing loss but 13 had secretory otitis media. Measurement of brainstem auditory evoked potentials is an accurate method of identifying sensory neural hearing loss in very preterm infants. PMID- 4038867 TI - Vascular basis for malformations in a twin. AB - A twin is described who was born with ileal atresia and hydranencephaly, the co twin having died at about 24 weeks' gestation. If a macerated or autolysed twin is found at birth, the paediatrician should be alerted to the possibility of serious and not immediately obvious defects in the surviving infant. PMID- 4038868 TI - Functional palatal incompetence and teratogenesis. PMID- 4038869 TI - Resection of pulmonary metastatic choriocarcinoma in 43 drug-resistant patients. AB - A regimen of multiple intermittent intensive doses of chemotherapy (chiefly 5 fluorouracil) was used in a series of 806 women with choriocarcinoma and malignant mole. The rate of complete remission of choriocarcinoma was 78.6%, and approximately 85% of the patients survived for more than 5 years. From 1962 through 1982, pulmonary metastatic choriocarcinoma was found to be resistant to chemotherapeutic agents in 43 of these patients; they subsequently underwent lung resection. There were no postoperative deaths, and the 5-year survival was 50%. These are relatively good results for patients with long-standing and widely disseminated choriocarcinoma. Human chorionic gonadotropin titer in urine and blood and variations of lung shadows are important criteria in selecting candidates for lung resection. For preservation of lung function, simple lobectomy is the first choice. Better long-term survival was obtained in patients who had a solitary lung lesion on admission without other major organ metastases and in those in whom the lung lesion was well encapsulated and became necrotic after chemotherapy. PMID- 4038870 TI - Familial postpartum transient hyperthyroidism. AB - Postpartum painless thyroiditis with transient hyperthyroidism is being recognized with increasing frequency. Evidence tends to support an autoimmune cause. We treated a 33-year-old woman who experienced typical postpartum painless thyroiditis. Her sister had had a similar episode 13 years previously, and their mother had had postpartum hyperthyroidism 42 years earlier. We believe that this familial association provides further support for autoimmunity in postpartum thyroiditis. PMID- 4038871 TI - Contrast-induced seizure associated with thrombotic thrombocytopenic purpura. Case report. AB - A patient with thrombotic thrombocytopenic purpura had a seizure as the result of a contrast media injection given during computed tomographic examination. To our knowledge, ours is the first such case reported. PMID- 4038873 TI - Some cons of PROs. PMID- 4038872 TI - The hypereosinophilic syndrome presenting with eosinophilic mastitis. AB - A case of the hypereosinophilic syndrome presenting with eosinophilic mastitis is described. The histopathology of the mastitis is illustrated and the patient's clinical course reported. PMID- 4038874 TI - Cisplatin potentiation of radiotherapy. Long-term follow-up. AB - Thirty-three patients with inoperable squamous cell carcinoma of the head and neck were treated with cisplatin, 15 mg/sq m, administered synchronously with high-dose radiation therapy. Twenty-nine patients (88%) responded to the regimen; of these, 20 had complete regression of all disease. Eight of the 20 had a relapse in less than one year of their treatment. Among those patients who did not have a relapse, the follow-up period was short. It is concluded that a clinical regression response is more likely with this treatment regimen than with radiation therapy alone, and that that response may be a better palliation. Further study of this combination of treatment modalities is warranted. PMID- 4038875 TI - Tetraphenylphosphonium ion is a true indicator of negative plasma-membrane potential in the yeast Rhodotorula glutinis. Experiments under osmotic stress and at low external pH values. AB - In the yeast Rhodotorula glutinis, accumulation of the tetraphenylphosphonium ion (TPP+) was increased under conditions of osmotic stress, indicating a hyperpolarization of the negative membrane potential (delta psi). The following observations were consistent with the occurrence of hyperpolarized delta psi: enhanced accumulation of glucosamine, the uptake of which is also driven by delta psi; increased respiratory rate. The accumulation of TPP+ was gradually decreased by lowering the pH of cell suspensions. At pH values below 4.5, no TPP+ was taken up, but instead thiocyanate (SCN-) was accumulated, indicating a positive delta psi. The pH-dependent influx of glucosamine followed the pattern of TPP+ accumulation both in the wild-type and in the nystatin-resistant mutant, M67, which displayed a negative delta psi down to pH 3. Thus TPP+ accumulation in Rh. glutinis reflected actual electrical potential difference across the plasma membrane. PMID- 4038876 TI - A simple method for purification of rat hepatic microsomal cytochrome b5. AB - Rat hepatic microsomal cytochrome b5 was purified to homogeneity by solubilization with the detergent Lubrol 12-A9 and chromatography on Fractogel TSK DEAE-650(S). The protein was obtained in high yield (52-87%) in 8 h, and only one polypeptide band, of Mr 16 600, was visible after sodium dodecyl sulphate/polyacrylamide-gel electrophoresis. PMID- 4038877 TI - Stimulation of tyrosine protein kinase activity by dimethyl sulfoxide. AB - Dimethyl sulfoxide (DMSO) stimulated the activity of a partially purified tyrosine protein kinase from rat lung. The stimulation was concentration dependent with a maximum stimulation (about 2 fold) observed at 10 per cent (V/V) DMSO. On the other hand, acetone (10 percent, V/V), did not exert any stimulatory effect on the enzyme activity. The stimulation was associated with a decrease in the Km for the substrate and an increase in the Vmax. In contrast, the Km for ATP was not affected by DMSO. Under identical assay conditions, DMSO did not significantly alter the activities of phosphorylase kinase, catalytic subunit of cAMP-dependent protein kinase and Ca2+-phospholipid-dependent protein kinase. It may be speculated that stimulation of tyrosine protein kinase may be one of the mechanisms by which DMSO exerts its biological effects. PMID- 4038878 TI - Adenosine 5'-(beta, gamma-imino)triphosphate and guanosine 5'-O-(2 thiodiphosphate) do not necessarily provide non-phosphorylating conditions in adenylate cyclase studies. AB - Commercial preparations of adenosine 5'-(beta, gamma-imino)triphosphate (App(NH)p) were found to be contaminated with a GTP-like substance(s) as well as a phosphate donor(s) for GDP. Thus, when these preparations were used as substrate with no purification, GDP was as effective as GTP in promoting PGE1 stimulation of human platelet adenylate cyclase. With purified App(NH)p as substrate, the effect of PGE1 with GDP was reduced but still observable, while that with GTP was unaltered. PGE1 also caused a stimulation in the presence of guanosine 5'-o-(2-thiodiphosphate)(GDP beta S) with ATP as substrate. Both of the PGE1-stimulated activities observed with GDP and its analog were completely lost by the addition of UDP, thereby, inhibiting GTP formation catalyzed by membrane associated nucleoside diphosphate kinase. The results demonstrate that the stimulatory effects of PGE1 observed with GDP and App(NH)p, and with GDP beta S and ATP were transphosphorylation dependent and, therefore, the analogs must be used with special caution in adenylate cyclase studies. PMID- 4038879 TI - A highly sensitive assay for glutathione transferase using 4,5-dihydro epoxybenzo(a)pyrene as substrate. PMID- 4038880 TI - Thrombotic thrombocytopenic purpura developing during pregnancy in a C2-deficient patient with a history of systemic lupus erythematosus. PMID- 4038881 TI - Non-protein bound oestradiol, sex hormone binding globulin, breast cancer and breast cancer risk. AB - It has recently been found by various authors that despite a normal serum concentration of oestradiol (E2), the percentage of non-protein-bound or free E2 is abnormally high in breast cancer patients. Since it is the free E2 which is considered to be biologically active, confirmation of this finding would be most relevant to the pathogenesis of breast cancer. Using Hammond's centrifugal ultrafiltration dialysis method we have measured free E2 in heparinized plasma from 68 premenopausal women (a) at high familial risk of breast cancer (n = 18), (b) with benign breast disease (n = 17), (c) cured of T1N0M0 breast cancer at least 6 months previously (n = 17) and (d) normal controls matched for age, parity and Quetelet index (n = 16). Sex hormone binding globulin (SHBG) was measured as [3H]-dihydrotestosterone binding capacity. Free E2 and SHBG were also measured in the serum of (e) postmenopausal patients having breast cancer (n = 38) and (f) matched control cancer patients (n = 67). We confirmed a very good inverse correlation between log free E2 per cent and log SHBG (P less than 0.0001). The regression lines for groups (a)-(d) were not statistically different. The regression lines for groups (e) and (f) were identical and ran nearly parallel to those for groups (a)-(d) though somewhat lower. This small difference may be ascribed to menopausal status. Therefore, we found no difference in free E2 percentage, calculated free E2 concentration or SHBG between premenopausal women at risk, women with benign breast disease, patients cured for early breast cancer or having breast cancer and matched controls. However, postmenopausal breast cancer patients had a significantly higher total serum E2 concentration and, by consequence a higher calculated free E2 concentration compared to the carefully matched control group. PMID- 4038882 TI - Hormonal studies in women with premenstrual tension. AB - Serum hormone concentrations were determined at intervals during the last 17 days of the menstrual cycle in 35 patients with premenstrual tension (PMT) and 11 control subjects without symptoms. The maximum mean concentration of oestradiol occurred 17 days before menstruation in the patients and 14 days before in the controls. The maximum concentrations of progesterone were similar in the two groups but the mean concentrations rose earlier in the cycle in the patients with PMT. These results suggested that the patients tended to ovulate earlier in the cycle than the controls and on the basis of the ovulatory surge in gonadotrophins two groups could be identified, group A who showed signs of ovulation 14 days or less before menstruation (17 patients, 9 controls) and group B who ovulated more than 14 days before menstruation (18 patients, 2 controls). There were no significant differences between the groups in prolactin, thyroid stimulating hormone or testosterone levels, but cortisol concentrations were uniformly higher in both groups of patients compared with those in the controls. Follicular growth was assessed with ultrasound in 18 patients and 16 control subjects. Mean follicular diameters were significantly lower in the patients than in the control group at the time of ovulation. Oestradiol determinations done at the same time correlated with the diameters and were also significantly lower in the patient group. The results suggest that ovulation tends to occur prematurely in women with PMT. PMID- 4038884 TI - Model for interactions of amino acid side chains with Watson-Crick base pair of guanine and cytosine: crystal structure of 9-(2-carbamoylethyl)guanine and 1 methylcytosine complex. AB - As a model of interaction between the guanine-cytosine base pair and carbamoyl group, the crystal structure of 9-(2-carbamoylethyl)guanine-1-methylcytosine complex has been studied by X-ray method. The crystal data are a = 8.540 (1) A, b = 12.693 (3) A, c = 14.249 (2) A, beta = 94.02 (1) degrees, space group P21/c, Z = 4, dm = 1.50, dc = 1.49 g cm-3, and R = 0.10 for 1035 reflections. The bases form a Watson-Crick pair, and the carbamoyl group is hydrogen bonded with O(6) of guanine and N(4) of cytosine in the adjacent pairs. A structural correlation has been found between the hydrogen-bonding pattern and the secondary structural fitting of alpha-helical segment with B-form DNA. PMID- 4038883 TI - Physiological and pathobiological significance of ocular glycoproteins. I. Studies using fluorescein labelled glycine max. AB - Cell surface carbohydrates play an important role in several biological, immunological, and neoplastic phenomena including development, growth regulation, cellular locomotion, receptor activation, and tumour metastasis. Fluorescein labelled lectins which bind to specific carbohydrate residues in glycoproteins and glycolipids are being increasingly used as chemical probes to study cell components. Several different preparations of ocular tissues from human, rabbit, and rat were examined for the distribution of N-acetyl-D-galactosamine (D-gal NAc) by means of fluorescein-labelled lectin from soybean (glycine max). A very strong fluorescence was observed in the corneal epithelium; Descemet's membrane and corneal endothelium were also strongly fluorescent. The conjunctival epithelium similarly showed a strong reaction, as did the goblet cells. The iris epithelium and the dilator pupillae were only weakly fluorescent, but the ciliary body showed strong fluorescence, as did the blood vessels. As compared with lens fibres the lens epithelium was strongly fluorescent. The outer retina, that is, the photoreceptors, the pigment epithelium, and Bruch's membrane, showed a very strong reactivity. The optic nerve showed moderate fluorescence, but reaction with extraocular muscles was variable. The skin of the upper and lower eyelids, hair follicles, and blood vessels showed strong lectin binding. Sections of retinoblastoma and malignant melanoma showed no reaction. The physiological and pathological significance of these findings is discussed. PMID- 4038885 TI - Peroxidation of liposomes in the presence of human erythrocytes and induction of membrane damage of erythrocytes by peroxidized liposomes. AB - Hemolysis (Kobayashi, T., Takahashi, K., Yamada, A., Nojima, S. and Inoue, K. (1983) J. Biochem. 93, 675-680) and shedding of acetylcholinesterase-enriched membrane vesicles (diameter 150-200 nm) were observed when human erythrocytes were incubated with liposomes of phosphatidylcholine which contained polyunsaturated fatty acyl chains. These events occurring on erythrocyte membrane were inhibited by radical scavengers or incorporation of alpha-tocopherol into liposomes, suggesting that lipid peroxidation is involved in the process leading to membrane vesiculation and hemolysis. The idea was supported by findings that generation of chemiluminescence, formation of thiobarbituric acid reactive substance, accumulation of conjugated diene compounds in liposomes and decrease of polyunsaturated fatty acids in liposomes occurred concomitantly during incubation. Hemolysis was also suppressed by the addition of extra liposomes, insensitive to peroxidation, or of serum albumin even after the completion of peroxidation of liposomes. These results suggest that peroxidized lipids, responsible for vesiculation and hemolysis, may be formed first in liposomes and then gradually transferred to erythrocyte membranes. The accumulation of these lipids peroxides may eventually cause membrane vesiculation followed by hemolysis. PMID- 4038887 TI - Ascorbic acid regulation of 3-hydroxy-3-methylglutaryl coenzyme A reductase activity and cholesterol synthesis in guinea pig liver. AB - Guinea pigs fed a normal diet show the expected diurnal variation in 3-hydroxy-3 methylglutaryl coenzyme A reductase activity. Vitamin C deficiency, however, suppresses the diurnal peak activity of reductase, due to a decrease in active (unphosphorylated) enzyme. Inhibition of reductase is paralleled by both a fall in hepatic cholesterol synthesis and a rise in serum cholesterol. Incubation of normal guinea pig hepatic microsomes with physiologic and supraphysiologic concentrations of sodium ascorbate also leads to a concentration-dependent inhibition of reductase activity. Thus, dietary extremes of vitamin C may exert similar effects on reductase activity and cholesterolgenesis. Moreover, the changes in enzyme activity induced by ascorbic acid appear to be due in part to a direct effect of the vitamin on the microsomally bound enzyme. PMID- 4038886 TI - Glucose transport by uterine plasma membranes. AB - Uterine plasma membrane preparations were obtained by centrifugation on discontinuous sucrose gradients. The specific activity of the plasma membrane marker 5'-nucleotidase was increased 10-fold while the specific activity of glucose-6-phosphatase was increased 3-fold. Electron microscopy showed mainly closed vesicles having diameters mainly in the range of 0.1 to 0.4 micron and an absence of other recognizable organelles such as mitochondria. D-Glucose transport was inhibited by sulfhydryl reagents, phloretin, and cytochalasin B. Uptake was prevented at high osmotic pressures. The Km of glucose transport was 12.2 +/- 1.1 mM. Studies of the inhibition of [3H]cytochalasin B binding by D glucose indicated that the value of the Kd of the cytochalasin B-transporter complex was larger than 1 microM. These data demonstrate the potential usefulness of these preparations in the study of glucose transport in rat uterus and its control by steroid hormones. PMID- 4038888 TI - High tyrosine-specific protein kinase activity in normal human peripheral blood lymphocytes. AB - Tyrosine-specific protein kinase (ATP:protein phosphotransferase, EC 2.7.1.37) activity was measured in normal human nonadherent peripheral blood lymphocytes using synthetic peptide substrates having sequence homologies with either pp60src or c-myc. A high level of tyrosine-specific protein kinase activity was found associated with the cell particulate fraction (100 000 X g pellet). High-pressure liquid chromatography and phosphoamino acid analysis of the synthetic peptide substrates substantiated the phosphorylation of tyrosine residues by the particulate fraction enzyme. The human enzyme was also capable of phosphorylating a synthetic random polymer of 80% glutamic acid and 20% tyrosine. Enzyme activity was half-maximal with 22 microM Mg X ATP and had apparent Km values for the synthetic peptides from 1.9 to 7.1 mM. The enzyme preferred Mg2+ to Mn2+ for optimal activity and was stimulated 2-5-fold by low levels (0.05%) of some ionic as well as non-ionic detergents including deoxycholate, Nonidet P-40 and Triton X 100. The enzyme activity was not stimulated by N6;O2'-dibutyryl cyclic AMP (100 microM), N6;O2'-dibutyryl cyclic GMP (100 microM), Ca2+ (200 microM), insulin (1 microgram/ml) or homogeneous human T-cell growth factor (3 micrograms/ml) under the conditions used. Alkaline-resistant phosphorylation of particulate proteins in vitro revealed protein bands with Mr 59 000 and 54 000 suggesting that there are endogenous substrates for the human lymphocyte tyrosine protein kinase. PMID- 4038889 TI - Alterations in cholinergic receptors mediate the effects of dexamethasone on corticosterone. PMID- 4038890 TI - Metabolic fate of O-[4-[(4-chlorophenyl)thio]phenyl] O-ethyl S-propyl phosphorothioate in a lactating cow. PMID- 4038891 TI - The effect of synthetic ovarian hormones on an in vivo model of thrombosis in the rat. AB - The effects of endogenous and exogenous, synthetic ovarian hormones on thrombus formation have been examined using an in vivo model in the rat. Thrombus formation in female rats was greatest during the di-oestrus stage of the oestrous cycle. Thrombus formation in both male and female rats was reduced following 6 weeks treatment with the oestrogen, ethynyl oestradiol whilst in females the progestogen, norethindrone acetate had no effect. These findings are in contrast to the increased risk of thromboembolic disorders reported in women taking oral contraceptives. The inhibitory effect of ethynyl oestradiol was not due to changes in blood flow but was dependent on the heparin concentration, being greatest at the highest heparin concentration used. Thrombus formation was greater in male rats than in females, a sex difference which is consistent with the higher incidence of cardiovascular disease in men than in women. PMID- 4038893 TI - Supraspinal and spinal mediation of naloxone-induced morphine withdrawal in rats. AB - Unanesthetized rats, made physically dependent over 5 days by chronic intra arterial infusion of increasing concentrations of morphine (35-100 mg/kg/day) underwent withdrawal by naloxone (6 micrograms) injection into either the lateral ventricle (i.c.v.), fourth ventricle (V4), intrathecal subarachnoid space (i.t.), or intra-arterially (i.a.) and were evaluated for cardiovascular and behavioral signs of precipitated abstinence. Naloxone i.c.v. produced a significantly greater increase in the magnitude and duration of withdrawal hypertension than did V4 injection. Naloxone i.t. produced a distinctively different, persistent, pressor response as compared to i.c.v., V4 or i.a. routes of administration, although no quantitative differences in behavioral signs of withdrawal were observed. Morphine-dependent, spinal transected (C1) animals generated an augmented pressor response to i.c.v. or i.t. naloxone. This pressor response was accompanied by a significant reduction in core temperature (0.50-0.79 degrees C). Both the naloxone-induced pressor and hypothermic responses were abolished by ganglionic (hexamethonium, 100 mg/kg, i.a.) or peripheral alpha-adrenergic (phentolamine 4 mg/kg, i.a.) blockade. The hypertensive and hypothermic effects of naloxone also were prevented in transected dependent rats by prior spinal pithing. We conclude that in morphine-dependent rats: supraspinal sites rostral to the V4 mediate a more intense naloxone-induced pressor response than caudal regions; cardiovascular and behavioral signs of withdrawal can be precipitated via the spinal cord of intact animals; and the production of withdrawal hypertension and hypothermia in spinal transected morphine-dependent rats indicates that these abstinence signs can be mediated through neuronal pathways within the spinal cord. PMID- 4038892 TI - Natural loss of Purkinje cells during development and increased loss with alcohol. AB - In untreated rats, degenerating Purkinje cells (P cells) were present from the 20th day of embryonic life (E20) to post-natal day 14 (PN14), but none was present on E17 or PN15. Ethanol increased the loss of P cells both before birth and up to PN6 or 8, but from PN10 no increased loss was seen. Most degenerating P cells were located below the P cell line. On PN3 ethanol killed some P cells in 12 h, and the first ultrastructural change was a dilatation of the nuclear double membrane after 8 h. Among the surviving P cells, natural cell death continued. Pentothal anesthesia on PN3 did not damage P cells. Exposure to ethanol from E12 to PN5 resulted in a large loss of P cells and retarded the foliation of the cerebellum. PMID- 4038894 TI - Normalization of dendritic spine numbers in rat hippocampus after termination of phenylacetate injections (PKU model). AB - Increased numbers of apical dendritic spines are present on hippocampal CA1 pyramidal cells in rats injected with phenylacetate from 2 to 21 days of life if animals are sacrificed at 20-30 days. However, if sacrificed at 60-90 days, spine counts are not significantly different from saline injected controls. These results suggest that this increased spine density at 3-4 weeks represents retardation of normal maturational spine loss rather than an actual hyperplasia, and is reversible upon termination of the phenylacetate injections. Implications for human pathologic series of phenylketonuria are discussed. PMID- 4038895 TI - Child labor in Bombay. AB - Of the world's largest child labor force in India, Bombay has over 30,000 working children, most of them migrants. In a prospective study of 73 working children from a part of Dharavi, the biggest slum in Asia, 68% were working as hotel boys; 22% had started working before their 10th birthday, a large number doing so to increase the family income, but earning less than Rs. 100 ($11) per month. Forty percent worked more than 12 hours a day and only 16% continued schooling. Two thirds depended entirely on their employers for food which was adequate and no child in the study was malnourished. Overall incidence of anemia and vitamin deficiency was 10% each. Only 7% had ailments related to their occupation. Because this was a cross-sectional study no conclusions can be drawn regarding long term and residual effects. Preventing children from working is likely to make worse their own as well as their families' problems unless substitute sources of income or welfare are available. Legal protection and other services near their working places are essential for those who have to work. PMID- 4038897 TI - The coming decade: unfinished tasks and new frontiers. PMID- 4038896 TI - Adapting Childhood Comes First for children. AB - In the present study, an attempt was made to adopt an intervention strategy from the principles expressed in Childhood Comes First: A Crash Course in Childhood for Adults (Helfer, 1978) to address the needs of abused children in a group format. The constructs underlying the tasks which comprise the crash course were generally found to be adaptable for use with children. They are: (1) sensory training; (2) self-acceptance; (3) self-control; (4) responsibility; (5) accepting one's own feelings; and (6) relating to others. The experience of working with seven abused children in a group which met weekly for six months to address these issues is described. PMID- 4038898 TI - Institutional abuse: tubal sterilization in a population at risk of ill-treating their children. AB - Among the 145 patients at risk of child abuse and neglect who were seen in 1980 in our institution in the prevention of child abuse and neglect prenatal clinic, 19 were sterilized after giving birth. The criteria applied to these 19 patients were compared to the common criteria applied to our general maternity population. We were able to prove that these common criteria were systematically disregarded in the case of a mother at risk of ill-treating her child. We further studied our approach from the angle of the conflict which could exist for health care professionals between the choice of leaving these women with the right to reproduce or putting an end to a history of ill-treatment of children. PMID- 4038899 TI - Analysis of sexual abuse hotline reports. AB - As concern about physical child abuse and neglect has increased, so too has the realization that children are also sexually exploited and abused. Yet, many protective service workers are often ill prepared to perform the difficult task of treating the abused child and his/her family. Through the analysis of sexual abuse hotline reports, the central aim of this study was to generate findings that would increase the knowledge base of protective service workers and private therapists engaged in treating sexually abused children and their families. To accomplish this task, and using seven classes of variables, analysis was performed on 205 substantiated cases of childhood sexual abuse. A number of important conclusions were discovered including: One-third of the cases had been reported to the agency previously; less than one-half (48%) of the victimized children were living with their natural fathers; natural fathers were identified as the perpetrator in 39% of the cases; and in contrast to other studies, a great number of cases (43%) involved vaginal intercourse between the victim and the perpetrator. Implications for treatment are also discussed, particularly in relation to improving resources and specialized training for workers involved in this highly sensitive area of practice. PMID- 4038900 TI - Social and legal ramifications of a child crisis line. AB - The article suggests the importance of a crisis line for children as a way of making it easier for them to report when they are abused or neglected. The Childhelp Line set up in Christchurch, New Zealand, in 1982, has shown that such a service is effective in reaching critical child and family situations not previously known to helping professionals. The Line is manned by carefully selected and trained volunteers. This has proved to have significant advantages, particularly in the absence of mandatory reporting of child abuse. The article also looks at the ambivalence towards the Childhelp Line expressed by parents, children, counselors, and the community, and at the legal issues raised by the service. PMID- 4038901 TI - The assessment of risk in child abuse and neglect case investigations. AB - Estimates vary, but statistics indicate that anywhere between one and six million children will be abused and/or neglected this year in the United States. In the process of investigating reports of abuse and neglect, child protective service workers are called upon to make numerous case decisions. Critical to much of this decision making is the assessment by the worker of the potential risk of harm that exists to the child regarding further abuse or neglect. This paper, based on two separate research studies, identifies the criteria child protective service workers use to assess this potential risk of harm to the child. The research also shows that the criteria are not used as individual factors that indicate the presence or absence of risk. Instead the criteria form a constellation of factors that function for the worker in assessing the degree of potential risk to the child. The article concludes with a discussion of the implications of research findings for child welfare practice. PMID- 4038902 TI - Unanticipated problems in the United States child protection system. AB - While the United States child protection system is widely recognized as probably the most sophisticated and wide-ranging in the world, it nevertheless has some inherent problems. This article addresses some of the negative effects of mandatory reporting and the lack of fit of a short-term crisis intervention treatment approach for a substantial proportion of the protective services population. Reporting may have detrimental effects on the client-reporter relationship. Further, over half of the cases investigated are not substantiated. Of concern are the impact on innocent families of being investigated and the waste of scarce worker resources on investigation. While some protective services families are well suited to a crisis intervention model, a large number are multiproblem families who are always in crisis and families with chronic problems for whom crisis intervention is totally inadequate. Furthermore, because of high caseload size, workers are often not available to intervene after they have investigated the case. The problems described have been exacerbated by funding cutbacks under the current United States administration. The child protection system, along with other social welfare programs, is at risk for being dismantled by the Reagan administration. PMID- 4038904 TI - Physical abuse in children under two: a study of therapeutic outcomes. AB - This study of physical abuse to children under the age of 2 addresses the prognosis of the family, compliance with treatment recommendations and the long term outcome of the child. Data were collected from a multidisciplinary evaluation team and from the Department of Human Services' records on 71 children. Nearly all families were referred for mental health counseling and parent training, but only 33% complied. Half of the children were abused more than once; 30% were abused after referral for counseling. The incidence of reabuse was unrelated to compliance with counseling. The majority of children had some out-of-home placement with a mean time in foster care of 11 months and in care of relatives for 24.4 months. In 69% of families, more than one child was abused. At the time of follow-up, 41% of children and 47% of siblings were not living with either parent. Half of the families were judged to be functioning poorly and only nine had made good progress in counseling. PMID- 4038903 TI - [Long-term follow-up of abused children (apropos of 65 cases)]. AB - The authors work in an area located north of Paris, which contains roughly a population of .75 million, of which 82,000 are children less than 3 years of age. The center and main city of the area is the town of Amiens. The recruitment of their cases under study was essentially hospital based, which explains the relative severity of the trauma observed. The children were followed by various observation systems. Seventy-four children, of which more than two-thirds were less than 3 years of age were followed for a period varying from two to ten years. Forty-three percent of these children have been maintained in their biological families; the others have been placed. With this system only nine recurrences of abuse have been observed (12%), and only two instances of death have been observed. Other studies have demonstrated higher proportions. However, in two-thirds of the children observed, there were minor or major psychological or even psychiatric sequelae. Protection services have tried to stay away from institutional placement as much as possible; when necessary, the foster home system or adoption has been used. Striking is the lack of means available to help abusing families. Efforts should be made to assist the abusing families stay together. PMID- 4038905 TI - Self-esteem and early background of abusive mothers. AB - Thirty-six mothers whose children had been abused were interviewed and compared with 36 mothers matched for social class and ethnic background. The abuse group mothers had lower self-esteem than the comparison mothers as judged by their desire that their children should not grow up to be like themselves or their partners. They were also less likely to discuss their problems with other people. They were less likely than the comparison mothers to have been brought up by their own parents. They had significantly more negative feelings than the comparison mothers towards their fathers when they were children and these negative feelings persisted into adult life. It is important that emphasis on treatment programs for these mothers should be placed on building up self-esteem and skills in interpersonal relationships. PMID- 4038906 TI - Child abuse and neglect in American Indian communities. AB - Child abuse and neglect have recently been found to occur among American Indians at rates comparable to other American population groups. Little is known about the clinical spectrum of Indian maltreatment, the psychodynamics and effective treatment modalities. Cultural misunderstanding, modernization, poverty, situational stress, poor parenting skills because of early break-up of Indian families, alcoholism, unusual perceptions of children, handicapped children, and divorce constitute factors associated with maltreatment in cases cited. Old solutions of removing children from families were largely inappropriate and ineffective and are being replaced by local efforts to develop foster homes, supportive family services, and legal procedures to protect children. Communication between agencies involved and mistrust of outsiders plus a lack of trained personnel and available community resources continue to pose major barriers to effective treatment and prevention efforts. Recent federal policies and laws clearly place the responsibility for child welfare in the hands of Indian tribes and tribal courts. The non-Indian health professional has an important but limited role in providing technical expertise and in aiding development of community resources, taking care to support but not usurp the emerging leadership of Indian people. PMID- 4038907 TI - Question and answer: genital herpes. PMID- 4038908 TI - Late infertile days in early postpartum cycles. AB - Luteal phase abnormalities in early menstrual cycles after pregnancy have been shown to cause confusion in the practice of natural family planning (NFP) for some patients and to restrict severely the number of late infertile days available to others. The cause of the abnormalities is uncertain but appears to be related to the nursing status of the patient. PMID- 4038909 TI - Alternative to retroperitoneal lymphadenectomy with preservation of ejaculation and fertility in stage I nonseminomatous testicular cancer. A prospective study. AB - Twenty patients with clinical Stage I nonseminomatous testicular cancer have been staged by retroperitoneal exploration and removal of landing zone lymphatics. Only two patients had microscopic metastases to these landing zone lymphatics and underwent retroperitoneal lymph node dissection. Two patients developed chest metastases in 2 to 5-year follow-up. All patients had preservation of ejaculation and their fertility status. This relatively brief surgical staging avoids the complications of a formal lymphadenectomy with 100% survival, and cost effectiveness with excellent quality of life due to minimal complications. PMID- 4038910 TI - Primary splenic angiosarcoma. Case report and literature review. AB - Primary splenic angiosarcomas are rare neoplasms. The diagnosis can only be made at surgery. Splenectomy prior to rupture prolongs survival. An unusual case report is presented and the literature reviewed. PMID- 4038911 TI - Cisplatin and doxorubicin. An effective chemotherapy combination in the treatment of advanced basal cell and squamous carcinoma of the skin. AB - Eleven patients with advanced basal cell carcinoma (BCC) or squamous cell carcinoma (SCC) of the skin were treated with cis-diamminedichloroplatinum II (cisplatin) and doxorubicin. Seven patients had prior surgery and six of these seven had prior radiation therapy. All patients had an adequate trial of chemotherapy. One patient received a second course of chemotherapy after relapse. Responses were seen in 10 of 12 (87%) of chemotherapy courses, and 5 of 11 patients (46%) have an unmaintained complete remission lasting 2 to 31 months. Toxicity was acceptable and consisted primarily of gastrointestinal side effects. These results indicate the combination of cisplatin and doxorubicin has significant activity in both advanced BCC and SCC of the skin. In addition, a portion of patients treated with the combination achieve a long-term unmaintained disease-free state. PMID- 4038912 TI - Combined radiation and chemotherapy for locally advanced transitional cell carcinoma of the urinary bladder. AB - A prospective study was performed on 22 patients with locally advanced transitional cell carcinoma of the urinary bladder to evaluate the toxicity and efficacy of an integrated treatment with cis-diamminedichloroplatinum (1.6 mg/kg body weight every 3 weeks for four cycles) and 60 G cobalt 60 or 18 MEV photons. Local and systemic toxicity caused by this treatment schedule was minor. Late sequelae consisted of contracted bladder in three patients. The rate of tumor free bladders after a mean follow-up of 14 months was 17 of 22. Distant metastases occurred in three patients. Local recurrence of superficial tumor elsewhere in the bladder was observed in two patients. Six patients died 4 to 10 months after initiation of the integrated therapy, three of these without evidence of disease. PMID- 4038913 TI - The role of chemotherapy and surgery in the treatment of retroperitoneal metastases in advanced nonseminomatous testis cancer. AB - This study evaluates the effect of combination chemotherapy on retroperitoneal metastases from nonseminomatous germ cell tumors of the testis (NSGCTT). Sixty six patients with Stage III or bulky Stage II NSGCTT with clinically documented retroperitoneal metastases first received systemic chemotherapy. Seventeen patients had minimal and 49 had advanced retroperitoneal metastases. The retroperitoneal metastases were classified as advanced if the patient had a palpable retroperitoneal mass, ureteral deviation on intravenous pyelogram, or a mass with a diameter greater than or equal to 5 cm documented by a computerized axial tomographic scan, a pedal lymphangiogram, or surgery. The patients with lesser but clinically evident retroperitoneal metastatic deposits were considered to have minimal retroperitoneal metastases. A complete remission of retroperitoneal metastatic deposits was achieved in 50 (76%) patients, with chemotherapy alone in 25 (38%), and with combined chemotherapy and surgery in 25 (38%). The resected deposits consisted of mature teratoma in 15 and malignant elements in 10. A complete remission using chemotherapy alone occurred in 13 of 17 (76%) with minimal and in 12/49 (24%) with advanced retroperitoneal metastases, and in 17/30 (57%) without and 8/36 (22%) with teratoma in the testis tumor. The data strongly implied that the bulk of the metastatic deposits was a more important prognostic variable than the histology of the primary tumor. The adverse relationship of a teratomatous differentiation on the response rates with chemotherapy alone was offset by the success of supplemental surgery. This study suggests the benefit of a postchemotherapy retroperitoneal lymph node dissection (RPLND) in patients with initially bulky retroperitoneal metastases (complete response [CR] increased from 24% to 67%; an additional 47% patients had no evidence of disease). The patients with minimal retroperitoneal metastases usually achieved a CR with chemotherapy alone. A routine RPLND after the chemotherapy is not indicated in patients with initially minimal retroperitoneal metastases. PMID- 4038914 TI - Production of erythropoietin-like activity by human renal and hepatic carcinomas in cell culture. AB - Two types of human cancers, a renal cell carcinoma and a hepatocellular carcinoma, were investigated in vitro; both produced a marked erythrocytosis in each patient. These tumors, when transplanted into athymic nude mice, produced a remarkable erythrocytosis in the host mice. To analyze this phenomenon, the primary cultures from these xenotransplanted tumors were performed. To obtain pure tumor cell cultures, cells derived from host nude mice were eliminated by the treatment with the antiserum raised against nude mouse cells. Epithelial cells derived from each tumor attached and grew in the cultures. The conditioned media from both tumor cells revealed high erythropoietic stimulatory activities. We have characterized these erythropoietin-like activities by size-exclusion high performance liquid chromatography. Three peaks of erythropoietin-like activities were noted after bovine serum albumin region. The molecular weights were estimated at about 55,000, 40,000, and 33,000, respectively. The results suggested that the human renal cell and hepatocellular carcinomas produced erythropoietin-like activities in vitro in culture and that erythrocytosis found in patients with cancer and in nude mice transplanted with the tumors was attributable to production of the erythropoietin-like activities by the tumor cells themselves. PMID- 4038915 TI - Isolated ectopic production of the free beta subunit of chorionic gonadotropin by an epidermoid carcinoma of unknown primary site. AB - Metastatic choriocarcinoma was suspected in a 39-year-old woman who presented 7 months postpartum with fatigue, pelvic pain, a massive pleural effusion, and a positive urine pregnancy test. Subsequent evaluation resulted in discovery of the isolated production of the free beta-subunit of chorionic gonadotropin (CG-beta) by a widespread, poorly differentiated epidermoid carcinoma. Chemotherapy was ineffective, the woman died, and at autopsy the primary site of the tumor could not be determined. The patient's serum (185 ng/ml) and a tumor metastasis (720 ng/g) contained large amounts of immunoactive material that diluted in parallel to CG-beta standard, but neither chorionic gonadotropin (CG), its alpha subunit, nor other placental proteins were detected. A monoclonal antibody that recognizes free CG-beta, but not intact CG, was instrumental in implicating an ectopic source of the CG-beta before a tissue diagnosis was obtained. When the patient's serum was chromatographed on a dextran gel, the CG-beta immunoactivity eluted in a position of higher apparent molecular weight than either standard CG or CG beta, suggesting that this neoplasm secreted an altered molecular form of the CG beta subunit. PMID- 4038916 TI - Karyotypic analysis and chromosome polymorphisms in four choriocarcinoma cell lines. AB - Four choriocarcinoma cell lines were karyotyped and examined for genetic homozygosity or heterozygosity using chromosomal polymorphisms. The BeWo, Jar, and ElFa lines had modal chromosomes in the hypertriploid range, while the DoSmi line was hypotetraploid. A number of chromosomal rearrangements were seen in all lines but there was no common rearrangement. The BeWo and Jar cell lines, derived from tumors following term births, were shown to be heterozygous by the presence of both X and Y chromosomes. The ElFa and DoSmi lines, established following molar pregnancies, were shown to be heterozygous; the ElFa line by the presence of both X and Y chromosomes and the DoSmi line by the examination of Q-band polymorphisms. Thus, all four lines, whatever their origin, were shown to be genetically heterozygous. PMID- 4038917 TI - Phase I and clinical pharmacological study of mercaptopurine administered as a prolonged intravenous infusion. AB - The bioavailability of oral mercaptopurine (MP) is poor, and plasma levels following p.o. dosing are highly variable. In an attempt to circumvent these problems, we conducted a Phase I trial and clinical pharmacological study of MP administered as a prolonged i.v. infusion. An infusion rate of 50 mg/sq m/h, which was designed to achieve therapeutic drug levels in plasma, was used in all patients. The infusion duration was escalated in 12-h increments. Thirty-eight patients were evaluated. The dose-limiting toxicity was mucositis. Other reversible toxicities were myelosuppression and hepatotoxicity. An infusion duration of 48 h was found to be safe, unassociated with dose-limiting toxicity. Objective responses were seen in five patients. The mean plasma steady-state MP concentration achieved was 6.9 microM with little interpatient variability seen. Allopurinol coadministration had no effect on the plasma pharmacokinetics of i.v. MP. However, allopurinol did alter the urinary metabolite pattern, decreasing thiouric acid and increasing MP and thioxanthine levels. The steady-state cerebrospinal fluid:plasma ratio for MP was 0.27, suggesting that this approach may be of value in the treatment of central nervous system cancer. MP can be safely administered as a 48-h i.v. infusion at a dose rate which reliably achieves MP levels associated with optimal antileukemic activity in vitro. PMID- 4038918 TI - Sequence-dependent synergism between dichloromethotrexate and cisplatin in a human colon carcinoma cell line. AB - We studied the cell killing effects of cisplatin (CDDP), 3',5' dichloromethotrexate (DCM), and different combinations of these drugs in a human colon carcinoma line (HCT-8). Using a clonogenic assay, the ED50 values for DCM were 3, 0.3, and 0.05 microM after 4-, 24-, and 48-hour exposure, respectively, while cell kill induced by CDDP was less time-dependent (ED50 values: 16, 7.8, 3.3, and 2.8 microM after 2-hour, 4-hour, 24-hour, and continuous incubation, respectively). Sequential exposure of these cells to DCM followed by CDDP resulted in synergism at every dose studied. The synergy was maximal with short DCM pretreatment intervals and decreased with increasing lengths of exposure to the antifol. In contrast, simple additive effects were observed when DCM was given together with or following CDDP. Considering the significant hepatic inactivation of both these compounds, our in vitro data encourage the design of clinical protocols with the sequence DCM----CDDP for hepatic arterial infusion treatment of liver metastasis from colon cancer. PMID- 4038919 TI - Parkinsonism following i.v. administration of high-dose metoclopramide used as an antiemetic agent during cancer chemotherapy. PMID- 4038920 TI - Enrichment of fibrillar cytoplasmic actomyosin in protoplasmic strands of Physarum polycephalum for the production of cell-free models. AB - The treatment of isolated protoplasmic strands of Physarum polycephalum with 2.5% ethanol in a physiological salt solution under isometric conditions induces the formation of a large amount of mostly longitudinally organized actomyosin fibrils in the endoplasmic channel, a region normally free of actomyosin fibrils. The quantity of fibrillogenesis as well as the concomitant force output during the induced contractures are dependent on the Ca++-content and the temperature of the test solution. The method was developed to optimize the structure of the plasmodial strands before their subsequent transformation into cell-free models by permeabilization and extraction of the strands. Cryosections of plasmodial strands containing cytoplasmic actomyosin fibrils stained with fluorescently labeled phallotoxins offer a further assay for the study of their contraction physiology under cell-free conditions. PMID- 4038921 TI - Pararenal angiosarcoma induced in male mice by 1,2-dimethylhydrazine--a model for studying the role of androgens in chemical carcinogenesis. AB - CBA male mice treated with 1,2-dimethylhydrazine (DMH) developed high incidence (up to 97%) of pararenal angiosarcomas. Castration that preceded DMH-treatment almost completely inhibited the induction of these tumours while castration that followed DMH-treatment had on influence on their development. Testosterone propionate (TP) was efficient in restoring the incidence of DMH-induced pararenal tumours in castrated males only when given simultaneously with DMH and was totally inefficient when given after the cessation of DMH-administration. Castrated CBA female mice developed 92% of pararenal angiosarcomas when they received combined treatment with DMH and TP; no such tumours appeared in the intact females treated with DMH alone. The incidence of pararenal tumours in males of different strains was as follows: CBA, 97%; (CBA X C57Bl)F1, 36%; C57Bl, 4%; C3H, 35%; BALB/c, 13%; C3HA, 7%. PMID- 4038922 TI - Effect of antigen stimulation on antigen-specific IgE-plaque-forming cells from peripheral-blood lymphocytes of atopics. AB - In the present study, it was shown that allergen challenge in vitro produced an increase in the number of antigen-specific IgE-plaque-forming cells of peripheral blood lymphocytes from grass- or ragweed-allergic patients. Thus, the blood lymphocytes of all twelve (four rye grass I and eight AgE) sensitive donors responded whereas the blood lymphocytes of five non-atopic controls were unresponsive to antigen challenge. Allergen challenge doses of 10(-10)-10(-12) g/ml were found to give the greatest number of plaque-forming cells whereas the number of plaque-forming cells at challenging doses between 10(-9) and 10(-7) g/ml were either the same or less than those obtained with unchallenged cells. The results are discussed as to whether this in vitro model system represents in vivo response to allergen of the allergic patient. PMID- 4038923 TI - In vitro IgE-secreting cells in man. I. Mitogen-independent and -dependent subpopulations. AB - In vitro IgE secretion by atopic and normal peripheral-blood lymphocytes was examined in culture with pokeweed mitogen or Staphylococcus aureus strain Cowan-I (StaCw) or without mitogen. IgE secreted in culture supernatants was measured with double antibody radioimmunoassay. Enumeration of IgE-secreting cells was made by a protein-A plaque assay. IgE was detected in increasing quantities in supernatants of cultured lymphocytes without mitogen up to the 12th day. IgE plaque-forming cells were formed by the lymphocytes in large numbers on days 4-7 in cultures with mitogen. These results suggest that not only mitogen-independent but also mitogen-dependent subpopulations may exist in the IgE-secreting cells. PMID- 4038924 TI - Serum sex-hormone binding globulin and mortality risk in postmenopausal women. PMID- 4038925 TI - Premenstrual syndrome. PMID- 4038926 TI - Aneuploidy of chromosome X, variants 22 and fra(17p12) PMID- 4038927 TI - Adverse effects of atrial fibrillation and syncope induced by calcium-channel blockers in hypertrophic cardiomyopathy. AB - Calcium-channel blockers are useful for the treatment of hypertrophic cardiomyopathy (HCM), but, their adverse effects, especially, those of diltiazem, have not been of much concern. Forty patients with HCM were treated with calcium channel blockers such as nifedipine, diltiazem, and verapamil. Atrial fibrillation was induced by diltiazem in two patients and verapamil induced syncope in one patient. The clinical and hemodynamic characteristics of the patients were as follows. All of them had the obstructive type of HCM (HOCM). One of them had a high pressure gradient of the left ventricular outflow tract and the others had earlier onset. In these patients, the left atrial overload seemed to be severe. The vasodilating action of calcium-channel blockers decreases the systemic pressure and in turn, may increase the pressure gradient and the left ventricular end-diastolic pressure. The elevated left ventricular end-diastolic pressure causes the left atrial overload which could be at risk of atrial fibrillation in patients with HCM. Therefore, calcium-channel blockers should be used carefully in peculiar cases of HOCM. PMID- 4038928 TI - Asynchronous washout of the liver as a sign of partial biliary obstruction. AB - This case is another example of the usefulness of hepatobiliary scan for the evaluation of biliary-enteric anastomoses and stresses the point that performing late scan could help reveal pathologic process in an obvious way. PMID- 4038929 TI - High incidence of gastric reflux during hepatobiliary imaging in pancreatitis. AB - A review of 100 consecutive hepatobiliary studies revealed eight cases in which there was prominent gastric reflux of the Tc-99m diisopropyl-IDA beginning 0.5 to 2.0 hours into the procedure. Five of these individuals had pancreatitis (four acute, one chronic). Hence, pancreatitis was involved in five out of eight of the studies with marked gastric reflux. A study of discharge records showed that a total of ten of the patients in this series had pancreatitis. Since only five showed prominent gastric reflux, the incidence was 50%. Other disorders accounted for the three remaining gastric reflux cases observed in 90 patients. PMID- 4038930 TI - Ontogeny of aggressive-sexual behavior between males in lines of Japanese quail (Coturnix coturnix japonica) selected for male mating frequency. AB - Japanese quail from lines bidirectionally selected for high and low male mating frequency and from the random-bred base population were observed in an ontogenetic study of aggressive-sexual behavior. Quail were reared in sex intermingled flocks until 28 days of age at which time half of the males from each line were housed as all-male flocks and half were transferred to individual cages. At 41 days of age, individually caged males exhibited mounting behavior to win encounters with other males. By 45 days, males from the high and control lines exhibited significantly more aggressive-sexual behavior than those from the low lines. Line x Rearing Experience interactions for mounting behavior at 45 and 56 days of age were due to the individually caged high- and control-line males' winning encounters by mounts; those maintained in flocks rarely mounted. Although some low-line males won encounters by mounts, occurrence of this behavior was infrequent. Males maintained in flocks were placed in individual cages at 57 days of age. When these males were compared with those housed in individual cages from 28 days of age, at 84 days of age and older, the Line x Rearing Experience interaction observed previously disappeared, and only differences among genetic lines were evident. Genetic and rearing experience effects are discussed as influencing agonistic and sexual behaviors. PMID- 4038931 TI - Predictors of dominance in male Betta splendens. AB - The formation of dominance/subordinancy relations in pairs of male Siamese fighting fish was examined in six experiments. Dominant animals typically were those fish that built the largest nests and that attacked an image of a live, displaying male most intensely prior to combat. However, pretest performance on an operant task and reaction to an animal's own mirror image were not useful predictors of subsequent dominance. These findings are consistent with the suggestion that domesticated Bettas have a territorial social strategy that includes both nest-building and fighting behaviors. PMID- 4038933 TI - Incidence of pup killing and parental behavior in virgin female and male rats (Rattus norvegicus): differences between Wistar and Sprague-Dawley stocks. AB - The responses toward young shown by males and nulliparous females differed substantially between two outbred stocks of laboratory rats. Sprague-Dawley females showed maternal behavior either spontaneously (35% of the naive rats) or through concaveation (92% of the initially neutral virgins). Of the Wistar females, however, only 10% showed maternal behavior spontaneously, and only 29% of the neutral virgins came to behave maternally during 15 days of concaveation. Prepubertal cohabitation with lactating rats did not facilitate maternal responsiveness in adulthood in the Wistar virgin females. Of the Sprague-Dawley males, 50% showed paternal behavior spontaneously, and only 4% killed the young. Among the Wistar males, however, only 4% showed paternal behavior spontaneously, and 76% killed pups. Such profound differences between outbred stocks of rats may be a source of discrepancies between the results of studies dealing with the induction of parental behavior in nonlactating rats. PMID- 4038932 TI - Prior-residence effect in Betta splendens. AB - Male Siamese fighting fish were presented with the visual image of an aggressive male conspecific for a 150-min test, with attack behaviors monitored continually. A 10-day period of residency in either the test tank or its exact replica resulted in more persistent attack than 10 min of residency. Testing in water other than that in which subjects had resided for 10 days did not produce a reduction in attack. Finally, the extent of attack behavior occurring early in testing was highly and positively correlated with subsequent attack duration; that is, at the start of an encounter, and before severe physical damage has been caused, Bettas may communicate to opponents their "intention" to engage in persistent, injurious aggression. PMID- 4038934 TI - The chinese hamster Don cell line differs from normal diploidy by one chromosome band. AB - G-banded and C-banded prometaphase and metaphase karyotypes of the Chinese hamster Don cell line from three different laboratories were compared. All the cell lines were pseudodiploid. Each consisted of two distinct cell populations designated S1 and S2. The chromosome complements of each of these populations differed from the diploid by only one additional chromosome band on a subterminal 1p in S1 and on a median 1q in S2. The sites of these extra bands were neither constricted nor heterochromatic. All other different karyotypes, including those from seven distinct subpopulations, had basic patterns of chromosome complements that were best represented by S1 or S2, respectively the major or minor cell type of the cell line. Moreover, nearly 80% of the metaphases analyzed had a modal chromosome number of 22, and about 60% had the same chromosome composition of a cell type or subtype. Our data also suggest that Don cells were probably pseudodiploid by 1964 or before. PMID- 4038935 TI - Pathologic features of sudden death in children, adolescents, and young adults. AB - Pathologic investigation of 50 children, adolescents, and young adults who died suddenly and unexpectedly revealed that the most frequently encountered cardiovascular diseases were mitral valve prolapse (12 cases), myocarditis (12 cases), hypertrophic cardiomyopathy (six cases), and anomalous origin of a coronary artery from the aorta (two cases). Five subjects had no evidence of cardiac abnormalities. A striking family history of sudden death was encountered among eight subjects, of whom three had mitral valve prolapse and three had normal hearts. Assessing the circumstances surrounding sudden death, it was found that at the time of collapse, 32 subjects were engaged in regular activity, eight subjects were engaged in active athletics, and ten were found dead in bed. A relationship of the terminal event to emotional stress was reported in three subjects. PMID- 4038936 TI - Pattern of genetic influence on pulmonary function. AB - Whether genetic factors influence small airway function and lung volume was examined in 20 adolescent (mean age, 16.2 +/- SD 1.1 years) monozygotic twin pairs, 11 adolescent (mean age, 16.7 +/- 0.7 years) dizygotic twin pairs, and 20 adult (mean age, 38.7 +/- 9.3 years) monozygotic twin pairs. Within-pair variances of adolescent dizygotic twins for height, FVC, FEV1/FVC, V50, V25, V50/FVC, FRC, and delta N2 were significantly larger than those of adolescent monozygotic twins, indicating that these pulmonary function variables are influenced predominantly by genetic factors in adolescence. Within-pair variances of adult monozygotic twins were similar to those of adolescent monozygotic twins in terms of V50 and V25, indicating that these pulmonary function variables are influenced predominantly by genetic factors in adulthood. These results indicate that small airway dynamics, in terms of V50 and V25, are influenced in larger part by genetic factors in adolescence as well as adulthood, whereas lung volumes in terms of FRC and FVC are controlled by genetics only in adolescence. PMID- 4038937 TI - [Hyperprolactinemia and its treatment (analysis of 107 cases)]. PMID- 4038938 TI - [Improved instruments for the reconstruction of urethral continuity in injuries of the urethra]. PMID- 4038939 TI - Coprophagy by foals: effect of age and possible functions. AB - In colts and fillies observed from birth to 24 weeks old, coprophagy occurred from Weeks 1 to 19. Its frequency was greatest during the first two months. Coprophagy was rarely observed in mares and stallions. Foals usually ate the faeces of their mother but were observed to eat their own and those of a stallion and another unrelated mare. Urination by the foal occurred before, during or after 26 per cent of the coprophagy incidents. It is hypothesised that foals may consume faeces in response to a maternal pheromone which signals the presence of deoxycholic acid or other acids which the foal may be deficient in and which it may require for gut immuno-competence myelination of the nervous system. Such a pheromone may also serve to accelerate growth and sexual maturation. Coprophagy may also provide nutrients and introduce normal bacterial flora to the gut. PMID- 4038940 TI - Biosynthesis and secretion of tremerogen A-10, a polyisoprenyl peptide mating pheromone of Tremella mesenterica. AB - The biosynthetic pathway of tremerogen A-10, a polyisoprenyl peptide mating pheromone produced by mating type AB cells of the heterobasidiomycetous yeast Tremella mesenterica, was investigated by immunological techniques with antibody specific to the peptide moiety of the pheromone. Using the biological assay and the radioimmunoassay of the pheromone and its related substances, it was suggested that the peptide is synthesized near the end of logarithmic phase of growth with a temporary accumulation of precursors in the cell. The precursors initially appeared in membrane-bound form and were subsequently converted to soluble forms prior to the secretion. The pheromone acquired its biological activity during the secretion. In the presence of tunicamycin or compactin, pheromone production was blocked with accumulation of membrane-bound precursors. Monensin, however, blocked pheromone production with accumulation of soluble precursors. The molecular species which accumulated in the presence of the antibiotics were analyzed by immunoprecipitation followed by sodium dodecyl sulfate/urea/polyacrylamide gel electrophoresis. In the absence of the inhibitors, membrane-bound precursors with molecular masses of 28 kDa, 12 kDa, 7.8 kDa and 2.8 kDa were found. The precursors which accumulated in the presence of tunicamycin and compactin were the 12-kDa and 28-kDa species, respectively. The results suggested that membrane-bound very high-molecular-mass precursors were initially formed and their extensive modifications, including glycosylation, farnesylation and proteolytic digestion, occur in the membrane. Based on these data, a biosynthetic and secretory pathway was postulated. PMID- 4038941 TI - Intracellular pH shift leads to microtubule assembly and microtubule-mediated motility during sea urchin fertilization: correlations between elevated intracellular pH and microtubule activity and depressed intracellular pH and microtubule disassembly. AB - The regulation of the microtubule-mediated motions within eggs during fertilization was investigated in relation to the shift in intracellular pH (pHi) that occurs during the ionic sequence of egg activation in the sea urchins Lytechinus variegatus and Arbacia punctulata. Microtubule assembly during formation of the sperm aster and mitotic apparatus was detected by anti-tubulin immunofluorescence microscopy, and the microtubule-mediated migrations of the sperm and egg nuclei were studied with time-lapse video differential interference contrast microscopy. Manipulations of intracellular pH were verified by fluorimetric analyses of cytoplasmic fluorescein incorporated as fluorescein diacetate. The ionic sequence of egg activation was manipulated i) to block the pHi shift at fertilization or reduce the pHi of fertilized eggs to unfertilized values, ii) to elevate artificially the pHi of unfertilized eggs to fertilized values, and iii) to elevate artificially or permit the normal pHi shift in fertilized eggs in which the pHi shift at fertilization was previously prevented. Fertilized eggs in which the pHi shift was suppressed did not assemble microtubules or undergo the normal microtubule-mediated motions. In fertilized eggs in which the pHi was reduced to unfertilized levels after the assembly of the sperm aster, no motions were detected. If the intracellular pH was later permitted to rise, normal motile events leading to division and development occurred, delayed by the time during which the pH elevation was blocked. Microtubule-mediated events occurred in eggs in which the intracellular pH was elevated, even in unfertilized eggs in which the pH was artificially increased. These results indicate that the formation and normal functioning of the egg microtubules is initiated, either directly or indirectly, by the shift in intracellular pH that occurs during fertilization. PMID- 4038942 TI - Neurotensin diminishes grooming and stimulates paper shredding behavior induced by water immersion of rats. AB - Intracerebroventricular (i.c.v.) administration of 2 micrograms neurotensin, a brain and gastro-intestinal peptide which elicits various behavioral responses, diminishes grooming but stimulates paper shredding behavior of rats evoked by water immersion. Neither naloxone (2 micrograms i.c.v.) nor haloperidol (2 micrograms i.c.v.) affect grooming and paper shredding behavior as observed following water immersion of rats. PMID- 4038943 TI - F-actin rings are associated with the ring canals of the Drosophila egg chamber. AB - Staining of Drosophila egg chambers with rhodaminyl-lysine-phallotoxin (RLP), a specific stain for F-actin, has demonstrated the presence of dense F-actin rings associated with the inner surfaces of the ring canals. They were first observed in the distal part of the germarium where rings of four different size classes were found, differing in diameter by up to twofold. The ring sizes are considered to correspond to the ring canals formed at each of four successive incomplete cleavages. During the growth of the egg chamber the actin rings were found to increase in diameter from less than 1 micron to approx. 10 micron. Concomitantly a secondary outer ring of more diffuse material is built up in association with the cell membranes. A well developed array of microfilament bundles was also associated with the nurse cell plasmalemma. In stages where the transfer of the bulk of the nurse cell cytoplasm into the oocyte was occurring the rings came closer together in a central area. In late stage chambers the F-actin rings and the microfilament bundles appeared to be incorporated into large irregular masses of actin, which subsequently disappeared as the mature oocyte formed. The F-actin rings are suggested to act as mechanical strengthening elements for the canal plasmalemma, whilst cytoplasmic transport occurs through the ring canals. PMID- 4038944 TI - Immunoglobulin E in aqueous humour. AB - The level of immunoglobulin E (IgE) was determined in the aqueous humour (AH) and serum by particle counting immunoassay (limit of sensitivity: 0.2 IU ml-1). This level in the AH was below 0.75 IU ml-1 in case of senile cataract (n = 22) and ranged from this assumed normal value to 550 IU ml-1 in case of uveitis (n = 37), Fuchs' cyclitis (n = 11), intraocular tumour (n = 7) and perforating ocular injury (n = 6). To know whether the IgE increase was related to a possible local production the AH/serum concentration ratio for IgE was calculated and divided by that for albumin. Values higher than 0.60 were considered as suggestive of a local synthesis and were observed in 31 of the 37 samples examined. PMID- 4038945 TI - Effects of H-Phe-Ile-Tyr-His-Ser-Tyr-Lys-OH on different behavioral tests of rats. AB - H-Phe-Ile-Tyr-His-Ser-Tyr-Lys-OH inhibited the extinction of active avoidance behavior 3 h and 6 h after administration and facilitated the learning of a T discrimination task. The peptide antagonized ECS-induced amnesia, if the treatment was performed 1 h before the test session. These results suggest that H Phe-Ile-Tyr-His-Ser-Tyr-Lys-OH can facilitate learning and memory processes. PMID- 4038946 TI - [Pharmacological properties of typical and atypical antidepressants in single and repeated administration]. AB - Pharmacological properties of some typical and atypical antidepressants administered repeatedly are more alike as compared to their effects attained after a single administration. PMID- 4038947 TI - [Effect of the antiemetic preparation dimetpramid on rat reproductive function]. AB - It has been demonstrated that dimethpramide exerted an adverse effect on the sexual glands of female rats. It provoked an inhibition of ovarian function (derangement of cycling rhythmicity, the loss of individual cycle stages) and depletion of energy resources of the uterus (drop of glycogen content). The reduction of the gonadotropic activity of the pituitary was also observed. PMID- 4038948 TI - Premarital socioeconomic roles and the timing of family formation: a comparative study of five Asian societies. PMID- 4038949 TI - [Clinical picture of X chromosome recessive ichthyosis]. PMID- 4038950 TI - Peripartal cardiomyopathy. AB - A case of peripartal cardiomyopathy diagnosed post partum by preoperative routine examination for a sterilization operation is discussed. Data from the literature show that 50% of the patients suffering from peripartal cardiomyopathy recover nearly completely; the other patients with distinct symptoms of cardial insufficiency die almost without exception from the disease. Current concepts of diagnosis and treatment are reviewed. PMID- 4038951 TI - Development of vocal recognition of mothers in infant Japanese macaques. AB - Individual vocal recognition was studied in infant Japanese macaques by presenting natural calls of mothers and nonmother cagemates to them in a habituation-dishabituation paradigm. Discriminability was measured by an increase in conditioned sucking response rate to a second stimulus call after habituation to the first stimulus call. Recovery from habituation was greater in subjects over 190 days postconception when mother's vocalizations were played back after the stimulus change than when sounds of others were presented. Results demonstrate that the subjects could sort acoustic variants of vocalizations given by their cagemates into at least two categories (mother versus others) and suggest that vocal recognition of mothers develops relative to postconception (maturational) rather than postnatal age in Japanese macaques. PMID- 4038952 TI - Home odor preferences in young hares (Lepus capensis syriacus): effects of age and role of maternal presence. AB - The odor preferences of mother-reared and hand-reared young hares between 1-30 days of age were studied. Subjects were exposed daily to three choice tests in which the following pairs of odors were presented: home cage odor (HCO)-neutral odor (NO); HCO-strange cage odor (SCO); SCO-NO. All young strongly preferred their HCO over SCO throughout the 30-day period. HCO was preferred over NO until the age of 20 days, while avoidance of SCO was shown during the first 10 or 20 days. The same experiment conducted on postweaned hares (31-50 days of age) revealed a strong preference for SCO over both HCO and NO. These findings may be interpreted with respect to the natural history of the hare and its unusual mother-young relationship, which, in the wild, is limited to a single daily meeting for nursing. It is suggested that the highly precocial hare recognizes and prefers its home odor independently of any maternal contribution to that odor, possibly relying on odor cues from its own body to return to its nursing site. Other possible advantages of these olfactory preferences, including predation avoidance and facilitation of social relationships, are discussed. PMID- 4038953 TI - Measures of growth, development, and sexual maturation in mongolian gerbils (Meriones unguiculatus): effects of photic period during ontogeny. AB - We examined, in Mongolian gerbils, the adequacy of two commonly used indices of rate of development, age at eye-opening and age at vaginal introitus, as predictors of biologically important events: initiation of feeding on solid food and age at first parturition. We then enquired as to the interrelationships among body weight, eye-opening, and vaginal introitus in Mongolian gerbils whose rates of development were manipulated by altering the extent of their exposure to illumination during ontogeny. We found that (1) age at vaginal introitus was significantly, but weakly, correlated with age at first parturition (Experiment I); (2) age at eye-opening strongly predicted age of initiation of gnawing on solid food (Experiment II); (3) eye-opening occurred at markedly different ages, but at the same body weight in gerbils reared under 0/24-, 6/18-, 12/12-, and 24/0-hr day-night cycles (Experiment III); and (4) vaginal introitus occurred at both different ages and different body weights in females reared under different day-night cycles (Experiment III). PMID- 4038954 TI - Thermal limitation of mother--young contact in Norway rats. PMID- 4038955 TI - Nocturnal penile tumescent evaluation of erectile function in insulin-dependent diabetic men. AB - This study compared nocturnal penile erections in four age-matched groups of young subjects: diabetic patients with and without erectile problems, psychogenically impotent men and healthy control subjects. All men were assessed under similar conditions during three nights, each for a total of 156 study nights. Diabetic impotent men exhibited a significantly decreased number of erectile episodes (p less than 0.05) and episodes of maximum tumescence per night (p less than 0.01). They also spent significantly less time in tumescence (p less than 0.005) and in simultaneous rapid eye movement sleep and tumescence (p less than 0.005). Diabetic men without sexual problems, psychogenically impotent men, and normal control subjects did not differ. Diabetic men in both groups spent less sleep time in rapid eye movement sleep and had longer latencies to onset of rapid eye movement. The decreased time in erection noted in impotent diabetic patients was no longer significant when adjusted for differences in duration of rapid eye movement sleep. In comparison to healthy control subjects and psychogenically impotent men, non-impotent diabetic men did show significantly diminished circumferential increases during erections, similar in degree to impotent diabetic patients (p less than 0.05). PMID- 4038956 TI - Diurnal changes in myoelectric spiking activity of the human colon. AB - Using an intraluminal probe supporting eight groups of electrodes, the myoelectrical activity of the proximal, transverse, and distal colon was recorded during 24-h sessions in 10 healthy subjects receiving evening and noon meals (greater than 800 kcal) and breakfast (less than 300 kcal). At each colonic site considered, the electromyograms exhibited two kinds of spike bursts: (a) short spike bursts localized at one electrode site and appearing rhythmically at a frequency of 10.6 +/- 0.3/min and (b) long spike bursts isolated or propagated orally or aborally. A peculiar pattern consisting of nearly permanent short spike bursts at a rate of 6.7 +/- 0.4/min was observed at the rectosigmoid junction. Computerized analysis of the duration of each kind of spike burst showed that the long spike burst activity increased by 63%-129% (p less than 0.05) during 2 h after each meal (but not after breakfast) at each colonic site. Furthermore, a significant (p less than 0.05) decrease in the long spike burst but not short spike burst activity was observed during sleep. These results provide evidence for circadian variations of colonic motility associated with eating and sleeping in the healthy human. PMID- 4038957 TI - [Megakaryocyte-fixed immunoglobulins in chronic idiopathic thrombocytopenic purpura in children]. PMID- 4038958 TI - [Action of high doses of monomeric IgG in treating children with chronic idiopathic thrombocytopenic purpura]. PMID- 4038959 TI - [Characteristics of the vascular link in the hemostatic system in hemorrhagic thrombocytovasopathies]. PMID- 4038960 TI - [Lipid peroxidation in hereditary thrombocytopathies]. PMID- 4038961 TI - [Estradiol, luteinizing hormone, testosterone and sex hormone-binding globulin in the clomiphene-induced menstrual cycle]. PMID- 4038962 TI - Surgical treatment for androphonia. An experimental study. PMID- 4038963 TI - [Chromosome studies in early human embryo stages]. PMID- 4038964 TI - Effects of gonadotrophin-induced elevation of serum testosterone upon somatomedin C levels and serum thymidine activity in children. AB - 3H-thymidine uptake into lectin-activated human lymphocytes allows to measure a growth-stimulating activity of serum, the thymidine activity (TA), which is GH dependent in vivo and related to somatomedins (Sm). In this work, it is shown: that addition of human chorionic gonadotrophin (HCG) or testosterone in vitro does not increase the 3H-thymidine uptake into lymphocytes; that the gonadotrophin-induced elevation of testosterone in children is accompanied by a significant increase of TA and, at a lesser degree, of Sm C; that these two increases are significantly correlated, and that the age-related variation of TA and Sm C after HCG stimulation test are not parallel. PMID- 4038966 TI - Regulation of urine marking in male and female mice: effects of sex steroids. AB - Effects of sex steroids on urine-marking activity were studied in male, female, and neonatally androgenized female mice. Urine marking was estimated by suspending ceramic tubes that were connected in a horizontal row with a steel rod into the home cage of an isolated mouse. Intact males showed high marking activity, which was diminished after castration. Both testosterone propionate (TP) and estradiol benzoate (EB) were effective in restoring the marking activity of castrated males, while 5-alpha-dihydrotesterone (DHT) did not have any stimulative effects. Intact normal females showed quite low marking activity and ovariectomy further depressed it. TP and DHT enhanced the marking of ovariectomized females, but EB restored the activity only to the preovariectomy level. In intact females which were neonatally androgenized, the marking activity was much higher than that of normal females. The pattern of the change induced by gonadectomy and hormone treatment in these females resembled that in males. Thus, ovariectomy reduced the activity and both TP and EB restored the level. These results indicate that the sexual dimorphism in the urine marking in mice is primarily determined by hormonal environment during early postnatal age. Hormonal control of scent marking is discussed in relation to the studies in other rodents. PMID- 4038965 TI - Decreased serum group-specific component protein levels and complexes with actin in fulminant hepatic necrosis. AB - Monomeric G-actin has recently been shown to form high-affinity complexes with group-specific component protein (Gc), and this process might be expected to occur in vivo when hepatocyte necrosis with release of actin takes place. We therefore measured serum Gc levels and searched for evidence of actin-containing complexes of Gc in 147 sera from 21 normal subjects and 126 patients with acute and chronic liver diseases. Sera were examined for Gc concentration using an ELISA with purified Gc as standard. Gc levels were greatly diminished (less than 10 mg per dl) in 5 of 37 patients with acute hepatitis and 1 of 3 patients with subacute hepatic necrosis, and the mean values for these groups overall as well as those for chronic active hepatitis patients were significantly less than that observed in the normal controls (mean, 35.5 mg per dl). No significant alteration in Gc level was observed in the chronic disease categories studied. In contrast, Gc concentrations less than 10 mg per dl were found in 12 of 14 patients with fulminant hepatic necrosis, and the mean for this group (9.7) was significantly reduced (p less than 0.001). Sequential studies in 12 patients with acute hepatitis of moderate to marked severity but without a fulminant phase showed significant diminutions in initial Gc levels when these were compared with Gc levels obtained during recovery. Using analytical isoelectric focusing with print immunofixation, variable amounts of Gc:G-actin complexes could be demonstrated in virtually all sera examined, but the proportion of total Gc present as complex with G-actin appeared greater in fulminant hepatic necrosis sera.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4038968 TI - OTA warns PPS pressure may alter ICU care. PMID- 4038967 TI - Crowding pregnant mice affects attack and threat behavior of male offspring. AB - Attack and threat behavior of adult male offspring of female mice crowded during the final third of pregnancy was investigated. In 5-min test pairings with an anosmic "standard opponent" which had 50 microliter of male mouse urine applied to its fur, the prenatally stressed group of males showed significantly less attack behavior; attack latency was longer and number of attacks, bites, amount of time spent attacking, and composite aggression scores were all lower, compared with the control group. Similarly, less threat behavior was observed in offspring from crowded dams; there were lower frequencies of tail rattles, rough grooms, and upright threats. Additionally, proportionally fewer males in the prenatally stressed group attacked or displayed threats. A second experiment was designed to investigate the effects of exogenous androgen on the aggressiveness of males from crowded mice: testosterone propionate administration (500 micrograms/animal/day, for 5 days prior to testing) abolished differences both in the proportion of males from crowded mice that fought and also apparently abolished differences in intensities of attack and threat behavior between groups. However, trends toward reduced aggression in prenatally crowded males remained. More detailed analysis of these responses, based only on animals that displayed aggression, revealed significantly reduced intensity of aggression in offspring from females crowded during pregnancy, indicating that testosterone propionate therapy did not completely restore this behavior. In order to reduce postnatal effects due to possible differences in mothering, all offspring were fostered to untreated mothers at birth. The results are discussed in terms of in utero exposure of male fetuses of crowded dams to stress-liberated adrenal steroids of maternal origin, and the possible consequences for the endocrine integrity of these offspring. PMID- 4038969 TI - Analysis of the fragile-X chromosome: localization and detection of the fragile site in high resolution preparations. AB - Fragile X chromosome preparations were analyzed at levels of up to 850 bands per haploid set. We were able to consistently sublocalize the Xqter fragile site to band Xq27.3 using high-resolution methods. Chromosome length versus the frequency of fragile X expression was also compared. The fragile site appeared at a higher percentage in more condensed chromosome preparations. The importance of this finding is that high-resolution chromosome preparations do not optimize fragile-X detection. PMID- 4038970 TI - Unusual sialilation of three different rare genetic variants of serum DBP: Gc1A17, Gc1A16, and Gc1A11. AB - The proteins of three anodal Gc1 variants, Gc1A16, 1A11, and 1A17, are characterized by the most acidic isoelectric points observed so far among the different Gc mutants. Stepwise removal of N-acetylneuraminic acid (NANA) by treatment with neuraminidase was performed to estimate the degree of sialilation of these Gc variants. The results indicate that both proteins, the anodal and the cathodal component of these Gc1 mutants, carry sialic acid residues. This observation is remarkable in so far as usually only the anodal component of the Gc1 protein contains NANA and only a single residue. From the experiments carried out it can be deduced that Gc1A16 has two NANA residues in the anodal and one NANA residue in the cathodal component. Gc1A16 was found in four members of three generations in a Danish family; the variant segregated as a Mendelian trait. More difficult to interpret are the results obtained with the variants Gc1A11 and Gc1A17. Gc1A11 probably has three NANA residues in the anodal and two NANA residues in the cathodal component. Gc1A11 has been observed in two mother-child pairs and is presumably also a simple genetic trait. Gc1A17 has also several NANA residues in both Gc proteins; it is suggested that the anodal component has either three or four NANA residues and the cathodal component either two or three NANA residues. Family information on this variant is not yet available. PMID- 4038971 TI - Inhibition of in vivo neutrophil accumulation by stress. Possible role of neutrophil adherence. AB - Psychological stress results in neural and endocrine changes which can alter various aspects of the immune system. However, the effects of stress on inflammation has not received much attention despite the fact that stress hormones, such as the corticosteroids, are known to reduce inflammation. The present study extends a previous finding that stress itself can reduce inflammation. In the first experiment, zymosan was injected into an air pouch on the dorsum of F344 rats. Half of these rats then received three hours of inescapable, intermittent, electric foot shock as a stressor. The other half of the injected rats served as nonstressed controls. A third group were given air pouches but no zymosan. Fewer neutrophils accumulated at the inflammatory site of stressed rats as compared to nonstressed control rats. However, phagocytosis of zymosan by air pouch neutrophils was higher in stressed rats. Peripheral perfusion was not altered significantly by shock, but vascular permeability was reduced in stressed rats. The effects of stress on peripheral blood leukocytes of rats not injected with zymosan was investigated. It was found that while peripheral blood monocytes and lymphocyte numbers were decreased by stress, neutrophils were not decreased. Increased neutrophil adherence was found in stressed rats. Additionally, in the presence of endotoxin, neutrophils from stressed rats did not increase their adherence as much as those of control rats. The increased adhesiveness of neutrophils in stressed animals may account for the diminished inflammatory response in the shocked rats. PMID- 4038972 TI - Promotion of tick cell growth by proline and fractions from tick eggs. PMID- 4038973 TI - Clinical applications of the argon laser. PMID- 4038974 TI - Quantitative radioautographic study of intracellular localization of calmodulin antagonist, W-7, in Chinese-hamster ovary cells. AB - The purpose of the present study was to analyse quantitatively the localization of calmodulin antagonist, n-(6-aminohexyl)-5-chloro-1-naphthalene-sulfonamide (W 7) in CHO-Kl cells. The cultured CHO-Kl cells were labelled with 1 (16.7 microM), 2 (33.4 microM), 5 (83.5 microM) and 10 microCi/ml (167 microM) tritiated W-7. Some cells were preincubated in 10, 50 and 100 microM unlabelled W-7 for 30 min and then labelled with 2 or 5 microCi/ml tritiated W-7 for 1 h. The cells were doubly fixed in glutaraldehyde and osmium-tetroxide solution, and embedded in Epon. For light-microscopic radioautography, 2 micron-thick sections were wet mounted with radioautographic emulsion and exposed for 1 month. The radioautograms showed that large numbers of silver grains were mainly localized in the cytoplasm as well as in the nucleus. Quantitative analysis demonstrated that, in both the cytoplasm and nucleus, the number of silver grains was dependent on the concentration of the administered tritiated W-7 and the number was dramatically decreased by the pretreatment of unlabelled W-7. These results show that, in CHO-Kl cells, the W-7 binding sites are saturable. It is concluded that W-7 may get into CHO-Kl cells and be bound to a specific protein that may be calmodulin protein. PMID- 4038975 TI - Measurements of radiation dose distributions for shielded cervical applicators. AB - Cervical applicators with shielded ovoids are employed to reduce dose to the rectum and bladder. Because of asymmetries introduced by the shields, dose distribution calculations for individual patients will require extensive computer reference data for the ovoid sources. Requisite 3-D dose distributions were measured for an unshielded and a shielded ovoid containing a Cs-137 source, using a computerized system employing a diode in a water phantom. The probe stops at each measurement point and accumulates dose for several seconds. The system automates horizontal positioning of the detector and angular motion of the ovoid to obtain dose in one plane. The detector is moved manually to other planes for a complete three dimensional set of measurements. In order to suppress the energy and directional dependence of the diode, final dose distributions are calculated from ratios of shielded to unshielded data in conjunction with independently measured TLD data for unshielded sources. PMID- 4038976 TI - Efficacy of lincosaminide antibiotics in the treatment of experimental staphylococcal mastitis in lactating mice. AB - Staphylococcus aureus is a frequent cause of bovine mastitis worldwide. A model that may predict the efficacy of antimicrobial agents in the treatment of bovine mastitis induced by Staph. aureus was developed in lactating mice. Infection was established by the inoculation of lactating CF1 mice with Staph. aureus into the mammary gland via the teat duct. At the dose of bacteria used, 85-90% of the inoculated, untreated animals developed a nonlethal, acute mastitis within 48 h. Antibiotic treatment was administered subcutaneously or by the intramammary route. Lincosaminide antibiotics including lincomycin, clindamycin, and pirlimycin were evaluated in this system. Other compounds which have been used in therapy of bovine mastitis including novobiocin, penicillin G, ampicillin, cloxacillin and rifamycin-SV were used as reference antibiotics. Pirlimycin was the most effective of the antibiotics tested in this standardized system. Depending upon the route of administration, this novel lincosaminide was 15 to 95 fold more effective than clindamycin, three- to six-fold better than lincomycin, two- to ten-fold more effective than novobiocin, 13- to 17-times more effective than cloxacillin and 8- to 22-times better than rifamycin-SV on a weight-dose comparison. Penicillin G and ampicillin were the least effective drugs tested against mastitis induced by the beta-lactamase producing strain of Staph. aureus used in these assays. Pharmacokinetic experiments suggested that the greater effectiveness of pirlimycin compared to clindamycin and lincomycin was due to increased affinity for and prolonged retention in the mammary gland. PMID- 4038978 TI - Involvement of protein sulfhydryls in the trigger reaction of rhodotorucine A, a farnesyl peptide mating pheromone of Rhodosporidium toruloides. AB - The involvement of protein sulfhydryls for the signaling of rhodotorucine A, a mating pheromone produced by mating type A cells of Rhodosporidium toruloides, was investigated by the use of sulfhydryl compounds. The sulfhydryl-blocking reagent 5,5'-dithiobis(2-nitrobenzoic acid) (DTNB; Ellman's reagent) strongly inhibited both the biological effect of the pheromone on the recipient cell and the hydrolysis of the pheromone, which is catalyzed by the mating type-specific surface endopeptidase of the recipient cell. Conversely, the two reactions were markedly enhanced by the presence of the reducing reagent dithiothreitol. The inhibitory effect of DTNB on the pheromone response of the recipient cell was specific to an initial stage of the differentiation; once it had initiated, the reagent had no effect on its progression. The results suggested that dithiothreitol enhances and DTNB impairs the efficiency with which the pheromone triggers sexual d differentiation. The reaction of DTNB with cellular protein sulfhydryls was highly restricted to those at the exterior surface of the membrane due to the impermeability of the reagent through the membrane. Phosphorylation of endogenous proteins, which is modulated by the pheromone added to an in vitro phosphorylation system, was also blocked by DTNB. The results showed that sulfhydryl groups are involved in the pheromone hydrolysis by the surface endopeptidase of the recipient cell and that pheromone metabolism is indispensable for the signaling reaction. We suggest that the modulation of protein phosphorylation of membrane proteins by the pheromone is an initial transmembrane response coupled to pheromone metabolism. PMID- 4038977 TI - Comparison of interlaboratory variation in amino acid analysis and rat growth assays for evaluating protein quality. AB - Estimates of inter- and intralaboratory variation of protein efficiency ratio (PER), relative PER (RPER), net protein ratio (NPR), relative NPR (RNPR), and nitrogen utilization (NU) were compared with those of amino acid analysis in the same batches of 7 protein sources (ANRC casein, egg white solids, minced beef, soy assay protein, rapeseed protein concentrate, pea flour, and whole wheat flour). Interlaboratory variation (estimated as between-laboratories coefficients of variation, CV) of NPR and RNPR (up to 6.0%) was lower than that of PER (up to 20.2%) and RPER (up to 18.5%). The interlaboratory determination of NPR and RNPR was also more reproducible than that of most essential amino acids (CV up to 10.0%), especially tryptophan (CV up to 23.7%), cystine (CV up to 17.6%), and methionine (CV up to 16.1%). Intralaboratory variation (estimated as within laboratories CV) of amino acid analysis (up to 4.7%), however, was comparable to that of protein quality indices in most protein sources (up to 6.0%). The significant (P less than 0.01) positive correlations (r = 0.68-0.74) between amino acid scores and protein quality indices based on rat growth were further improved when amino acid scores were corrected for digestibility of protein (r = 0.73-0.78) or individual amino acids (r = 0.79-0.82). PMID- 4038979 TI - Pseudocholinesterase and trait anxiety in premenstrual tension syndrome. AB - Volunteers (N=71) with premenstrual syndrome (PMS) were given the Peck-Abraham PMS Questionnaire and separated by resulting scores into mild, moderate, and severe groups. Fourteen subjects were randomly selected from each group. Pseudocholinesterase serum levels were measured on the first day of menses for all group members. Trait anxiety was measured by the State Trait Anxiety Inventory (STAI). Pseudocholinesterase, a possible marker for trait anxiety, was found elevated in 6 of 14 (43%) of the severe PMS subjects, in 2 of the 14 (14%) moderate PMS subjects, and in none of the mild PMS subjects. Trait anxiety was found in 8 of these subjects. None of the subjects with mild PMS showed trait anxiety, while 25% of those with moderate PMS and 75% of those with severe PMS showed trait anxiety. No subject with mild PMS had trait anxiety. In this study PMS is treated as a trait-dependent form of anxiety. PMID- 4038980 TI - Susceptibility of mice reconstituted with trisomy 19 hematopoietic cells to infection with Rauscher leukemia virus. AB - Radiation chimeras with trisomy 19 hematopoietic cells were constructed to test the sensitivity of the trisomic hematopoietic system to infection with Rauscher leukemia virus: Hematopoietic cells from livers of trisomic fetuses were rescued by transplantation into lethally irradiated adult mice. These Ts 19 radiation chimeras show a stable and sufficiently long-lived trisomic hematopoiesis to allow experimental induction of Rauscher leukemia. Rauscher leukemia virus (RLV) induced a marked proliferation of erythroblasts in the spleens of Ts 19 mice and control chimeras within 3 weeks. The onset of erythroblast proliferation was significantly delayed in the Ts 19 mice, suggesting a smaller number of target cells for the RLV and/or reduced susceptibility of the target cells to RLV. Both Ts 19 and control chimeras developed nonlymphocytic leukemia 2-4 months after RLV injection. The course of leukemogenesis was similar in the two experimental groups. No numerical chromosome abnormalities associated with leukemogenesis were detectable in Ts 19 or control cells. The numbers of chromosomal sister chromatid exchanges 2 weeks after RLV injection were elevated to the same degree in both Ts 19 and control cells. Thus, cells with constitutional trisomy do not show increased chromosomal instability due to leukemogenesis. PMID- 4038981 TI - Influence of the centrosome on the structure of nucleated microtubules. AB - The capacity of the centrosome to influence the lattice structure of nucleated microtubules was studied in vitro. Brain microtubules self-assembled to give predominantly (98%) 14-protofilament microtubules. However, under exactly the same conditions of assembly they grew off of purified centrosomes from neuroblastoma cells to give mostly (82%) 13-protofilament microtubules. Thus, the nucleation sites on the centrosome constrained the microtubule lattice to yield the number of protofilaments usually found in vivo. PMID- 4038982 TI - Monocyte procoagulant activity in glomerulonephritis associated with systemic lupus erythematosus. AB - Monocyte infiltration and activation of the coagulation system have been implicated in the pathophysiology of glomerulonephritis. In this study, spontaneous procoagulant activity (PCA) was measured in circulating mononuclear cells to determine whether elevated PCA correlated with the presence of proliferative glomerulonephritis in patients with systemic lupus erythematosus (SLE). No increase in PCA was found in 20 patients with end-stage renal failure, 8 patients with glomerulonephritis without SLE, and 10 patients undergoing abdominal surgical or orthopedic procedures as compared with 20 normal controls. In eight patients with SLE but with no apparent active renal disease, PCA was not elevated above normal basal levels. Seven additional patients with SLE who had only mesangial proliferation on biopsy also had no increase in PCA. In contrast, eight patients with focal or diffuse proliferative lupus nephritis, and one patient with membranous nephritis who ultimately developed a proliferative lesion, had a marked increase in PCA with greater than 100 times the base-line levels. The activity was shown to originate in the monocyte fraction of the mononuclear cells and was shown to be capable of cleaving prothrombin directly. The prothrombinase activity was not Factor Xa, because it was not neutralized by anti-Factor X serum and was not inhibited by an established panel of Factor Xa inhibitors. Monocyte plasminogen activator determinations did not correlate with renal disease activity. We conclude that monocyte procoagulant activity, a direct prothrombinase, seems to correlate with endocapillary proliferation in lupus nephritis and could be a mediator of tissue injury. PMID- 4038983 TI - Genetic regulation of immunoglobulin and specific antibody levels in twins reared apart. AB - We studied the effect of the same genetic but different environmental factors on total immunoglobulin and specific antibody levels in twins reared apart. Sera were analyzed from 26 monozygotic (MZ) and 10 dizygotic (DZ) twin pairs, who were separated on average 2 mo after birth and reared apart. Total IgM, IgG, and IgA were measured by single radial diffusion. Specific antibodies of each isotype to tetanus toxoid, and to polyvalent and type 14 pneumococcal capsular polysaccharides were measured by a solid-phase antigen-enzyme-labeled anti-Ig immunoassay. One-way analysis of variance showed intrapair total Ig and antibody levels to be more highly correlated in MZ compared with DZ twins. Our results indicate that genetic factors are more important than environment in regulating these humoral immune responses. PMID- 4038984 TI - Intracellular localization of the catalytic subunit from cyclic AMP-dependent protein kinase in mutant Chinese hamster ovary cells deficient in this enzyme. AB - A direct cytochemical procedure that specifically locates free catalytic subunits (C) from cAMP-dependent protein kinase has been used to follow the kinetics of kinase dissociation in parental Chinese hamster ovary cells (CHO 10001) and 4 mutant CHO cell lines variously deficient in this enzyme (CHO 10215, 10248, 10260, 10265) (1-5). When cultures of wild-type cells were stimulated with 8BrcAMP a time- and dose-dependent dissociation of kinase was observed. The catalytic unit appeared first in the cytoplasm and nucleolus and with time in the nucleoplasm as well. At peak protein kinase activation (30 min) more than 80% of the cells possessed abundant C in all of these subcellular compartments. The data indicate that both the type I and type II isozymes of the cAMP-dependent protein kinase are localized in similar areas of the cell. Stimulation of the mutant cell lines with 8-BrcAMP revealed that they each contained activatable kinase, determined cytochemically, that paralleled in amount the total assayable protein kinase determined biochemically (1-6). There were differences in the basal (unstimulated) levels of free C in the mutants relative to each other and to wild type cells. For example, wild-type and mutants 10248, and 10260 had barely detectable cytoplasmic catalytic-subunit in unstimulated cultures whereas mutant 10215 possessed a significant amount of free C. Upon stimulation with 8-BrcAMP, the subcellular distribution of C was in all cases similar; although there were significant quantitative disparities between the wild type and various mutant cell lines. All cell lines examined had roughly equivalent amounts of nucleolar C but differed predominantly in the quantity of cytoplasmic kinase. Specifically, two of the mutant lines (10260 and 10248) contained barely detectable amounts of nucleoplasmic C whereas the other mutants had moderate (10265) to near normal (10215) amounts of nucleoplasmic enzyme. Mutants having only type I isozyme (10248) and those with only type II isozyme (10265) gave similar patterns of free C localization after 8BrcAMP stimulation. PMID- 4038986 TI - Formal thought disorder in schizophrenics and their twins. PMID- 4038985 TI - Protein degradation in rumen and amino acid absorption in small intestine of lactating dairy cattle fed heat-treated whole soybeans. AB - Four lactating Holstein cows fitted with rumen cannulae and T-type cannulae in proximal duodenum and terminal ileum were used to measure protein degradation in the rumen and amino acid flow and absorption in the small intestine. Soybean meal, whole soybeans, and whole soybeans extruded at 132 and 149 degrees C provided 50% of the protein in diets that contained 51% grain, 36% corn silage, and 13% alfalfa hay (dry matter). Spot samples of digesta were collected from duodenum and ileum during 96 h, and lanthanum was an indigestible marker to estimate flow and digestibility of nutrients. With diaminopimelic acid as a microbial marker, apparent degradations of dietary crude protein in the rumen were 73, 80, 66, and 60% for diets containing soybean meal, whole soybeans, and whole soybeans extruded at 132 and 149 degrees C. Because of the extensive degradation of protein with the raw soybean diet, less total amino acids reached the duodenum, and because of decrease of availability, absorption from the small intestine (g/day) was lowest with this diet. Feeding diets containing extruded whole soybeans increased availability of total essential amino acids in the small intestine compared with diets containing soybean meal and whole soybeans. Absorption from the small intestine (g/day and percent entering) of individual amino acids was generally higher for extruded whole soybean diets. PMID- 4038987 TI - Babesia microti in an Indiana woman. PMID- 4038988 TI - Site-selective homing of antigen-primed lymphocyte populations can play a crucial role in the efferent limb of cell-mediated immune responses in vivo. AB - Lymphoid cells of the mammalian immune system exhibit special migratory properties within their in vivo environment. This fundamental characteristic is important to the protection of the organism from infection and neoplastic transformation by a process termed immunologic surveillance. The importance of lymphocyte recirculation was addressed by investigating the role of site selective homing of lymphocytes during the efferent phase of an in vivo adoptively transferred immune response. We approached this problem by using pertussis toxin (PT), a known inhibitor of lymphoid cell migration in vivo. PT is a protein secreted by the bacterium Bordetella pertussis, which induces a selective and long-lasting inhibition of the emigration of lymphocytes from the bloodstream into solid tissue. In this study, we demonstrate that the blockade of lymphocyte extravasation potential mediates inhibition of certain cell-mediated immune responses in vivo. We investigated the effect of PT on the extravasation of antigen-primed lymphocytes into solid tissue. The results show that the loss of lymphocyte homing potential after in vitro treatment of the primed cells with PT is accompanied by an inhibition of antigen-specific contact hypersensitivity after adoptive transfer. This result suggests that the process of lymphocyte extravasation into nonlymphoid tissue sites such as the skin shares fundamental similarities to the selective localization of circulating lymphocytes to lymph nodes. Furthermore, the inhibition of contact hypersensitivity observed after the i.v. adoptive transfer of PT-treated antigen-primed cells could be circumvented by transferring the PT-treated cells directly into a tissue site with the relevant antigen. In contrast, no inhibition in the number of antibody-forming cells present within the spleen was observed after an adoptive transfer of PT treated sheep red blood cell-primed lymphocytes, a result that is in agreement with radiotracer data. Thus, the inhibitory effect of PT on the adoptive transfer of contact hypersensitivity was established to be a direct result of the PT mediated alteration of cellular migration, because PT inhibits the entrance of lymphocytes into specific tissue sites without inhibiting other cellular functions. This conclusion is additionally supported by experiments that showed that lymphocytes that have been pretreated with PT exhibit normal in vitro responses, as assayed by mitogenesis in response to concanavalin A and by the differentiation and function of alloantigen stimulated or hapten-specific cytotoxic T lymphocytes.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 4038990 TI - Cryptosporidiosis. PMID- 4038989 TI - Rapid killing of actinomycin D-treated tumor cells by human monocytes. II. Cytotoxicity is independent of secretion of reactive oxygen intermediates and is suppressed by protease inhibitors. AB - Pretreatment with Actinomycin D (ActD, 1 microgram/ml for 3 hr) rendered WEHI 164 tumor cells susceptible to killing by human monocytes in a 6-hr 51Cr release assay. The present study was designed to elucidate the role of reactive oxygen intermediates (ROI) and of proteolytic enzymes in this reactivity. ActD-treated WEHI 164 cells did not trigger any measurable release of O-2 or H2O2 from monocytes. Monocytes exposed to phorbol-12-myristate-13-acetate, which enhanced release of ROI, did not show augmented killing of ActD-treated tumor cells. Scavengers of oxygen metabolites (catalase, superoxide dismutase, gluthatione, and mannitol), which inhibited ROI-mediated PMA-induced monocyte cytotoxicity against erythrocytes, did not affect monocyte killing of ActD-treated WEHI 164 cells. Enzymatically generated ROI with xanthine/xanthine-oxidase glucose/glucose oxidase did not show preferential killing of ActD-treated WEHI 164 cells. Two patients with chronic granulomatous disease had normal levels of monocyte cytotoxicity against ActD-treated tumor cells. To determine the possible role of proteolytic enzymes in mediating this reactivity, we studied various antiproteases. Organophosphorous agents (DFP and PMSF), chloromethyl-ketone derivatives of tosylamino acids (TLCK and TPCK), Actinomyces products (pepstatin and chymostatin), and the synthetic protease substrate TAME inhibited monocyte mediated cytotoxicity against ActD-treated WEHI 164 cells. The macromolecular protease inhibitors alpha-1 antitrypsin, bovine pancreatic trypsin inhibitor (BPTI), soybean trypsin inhibitor, and the synthetic protease substrate ATEE had little effect on monocyte cytotoxicity. When monocytes were preincubated with drugs for 1 hr and washed, TLCK, TPCK, and PMSF inhibited cytolysis, whereas the less effective chymostatin and TAME and the inactive BPTI had no effect under these conditions. Inhibition by preincubation with TLCK, PMSF, and TPCK was completely reversed after 6 hr of culture. Supernatants of monocyte cultures had lytic activity against ActD-treated WEHI 164 but not against untreated cells. Antiproteases inhibited the lytic activity of monocyte supernatants. These results strongly suggest that ROI do not play a critical role in monocyte mediated rapid killing of drug-treated tumor cells, and that proteolytic enzymes are involved in this reactivity. PMID- 4038991 TI - Binding capacity of sex-hormone-binding globulin and free testosterone determination in evaluation of hirsute women. AB - To investigate the relation between free testosterone (T) and binding capacity of sex-hormone-binding globulin (SHBG-BC) and a degree of hirsutism, 34 women were classified into 3 groups according to the criteria of Ferriman and Gallway on the degree of the hirsutism; 11 patients with a total score of 1 to 3 (group 1), 8 patients with a total score of 4 to 10 (group 2), and 15 patients with a total score of 11 or more (group 3). Total plasma T, SHBG-BC, and free plasma T were measured in each group, and they were compared with those of controls. In groups 1 and 2, mean levels of total T were slightly higher than in controls but the differences were not significant. Total T levels were extremely elevated in group 3. Mean level of SHBG-BC in group 1 was slightly lower than in controls but was not statistically significant. SHBG-BC was drastically reduced in groups 2 and 3. The percent free T levels and free T concentrations were significantly higher than those of controls in groups 2 and 3, but not in group 1. The results suggested that decreased SHBG-BC and increased free T might be the cause of hirsutism in women with normal total T levels. PMID- 4038992 TI - An aqueous-organic extraction method for the isolation and identification of psilocin from hallucinogenic mushrooms. AB - A simple aqueous extraction method for the isolation and identification of psilocin from Psilocybe cubensis mushrooms is reported. This method employs a dephosphorylation of the phosphate ester to psilocin, which facilitates a greater product yield and simplifies identification. Psilocin extracted by this method is sufficiently concentrated and free of cocontaminants to allow identification by infrared spectroscopy and gas chromatography/mass spectrometry. PMID- 4038993 TI - Dopamine agonist activity of EMD 23,448. AB - EMD 23,448 was examined in tests of dopaminergic function and was found to be an atypical dopamine (DA) agonist. EMD 23,448 was a weak or inactive DA agonist when examined in tests of normal postsynaptic DA receptor function: production of stereotypy in the rat (ED50 greater than 5.0 mg/kg i.p.); production of emesis in beagles (minimum effective dose = 81 micrograms/kg i.v.); and, enhanced locomotor activity of the mouse (no excitation in doses less than or equal to 50 mg/i.p.). Moreover, EMD 23,448 was relatively weak in competing for [3H]-apomorphine binding to rat striatal membranes (Ki, 205 nM). On the other hand, this indolyl-3 butylamine did activate supersensitive postsynaptic DA receptors. Specifically, it elicited contralateral turning in rats with a unilateral 6-hydroxydopamine lesion of the substantia nigra (ED50 value = 0.9 mg/kg) and did elicit stereotypy in rats given chronic daily haloperidol treatments. EMD 23,448 also exerted pharmacological effects in tests designed to measure activation of dopamine autoreceptors. It inhibited the gamma-butyrolactone-induced increase in striatal dopa levels (ED50 = 1 mg/kg i.p.) and produced a dose-related fall in the locomotor activity of the mouse. The results are discussed and contrasted with data derived for apomorphine and the putatively selective autoreceptor agonist (+/-)-3-PPP. PMID- 4038994 TI - The reaction of Pt-antitumor drugs with selected nucleophiles. I. The reaction of cis-[Pt(NH3)2Cl2] with glycine. AB - Various Pt(II)-glycine coordination compounds were characterized by 1H and 13C NMR spectroscopy, some of them also by electrophoretic and chromatographic behavior. The results were applied to the analysis of the reaction mixtures of cis-[Pt(NH3)2Cl2] and glycine obtained under various conditions. Cis [Pt(NH3)2Cl2] reacts with glycine to give cis-diammine-(glycine-N,O)-Pt(II) and cis-diammine-bis(glycine-N-)Pt(II). Their ratio depends primarily on the pH of the reaction medium. Conformation of these compounds is discussed based on the observed Pt-C and Pt-H NMR coupling constants. PMID- 4038995 TI - The reaction of Pt-antitumor drugs with selected nucleophiles. II. Preparation and characterization of coordination compounds of Pt(II) and L-histidine. AB - Various His-Pt(II) coordination compounds were prepared by reaction of K2PtCl4 or cis-[Pt(NH3)2Cl2](cis-DDP) with His and analyzed by 1H and 13C NMR spectroscopy, electrophoresis, and ion-exchange chromatography. His may be coordinated to Pt by the imidazol iminogroup and/or the alpha-aminogroup; the carboxygroup remains always free. Both bidentate as well as monodentate ligands were identified. Cis DDP reacts with His to give a mixture of compounds where all these possibilities are present: cis-diamine-(histidine-N,N-)Pt(II) and three different types of cis diammine-bis(histidine). HCl trans cleavage of compounds with bidentate His ligands leads to a mixture of two compounds having His ligated to Pt by an amino or imin group. The methods applied are suitable for analyzing reactions of His with cis-DDP under model conditions similar to physiological conditions. PMID- 4038996 TI - Unmasking of cerebellar tumours by amitriptyline in depressive patients. PMID- 4038997 TI - Lesions in nucleus basalis magnocellularis and medial septal area of rats produce qualitatively similar memory impairments. AB - The functional contribution of nucleus basalis magnocellularis (NBM) and the medial septal area (MSA) to memory was evaluated in two different spatial discriminations. Preoperatively, rats were trained to a criterion level of performance in a simultaneous left/right discrimination on the stem of a T-maze (a trial-independent memory) and a discrete-trial, rewarded alternation discrimination on the arms of the T-maze (a trial-dependent memory). Bilateral lesions were made by injecting ibotenic acid (IBO) into the NBM, MSA, both NBM and MSA, or dorsal globus pallidus (DGP), and by radiofrequency current (RF) in the NBM and MSA. Control rats received operations in which either no current was passed or no neurotoxin was injected. Lesions in the NBM, MSA, or both the NBM and MSA produced a similar pattern of behavioral changes relative to the performance of controls; postoperative reacquisition of the arm discrimination was initially impaired but showed recovery to normal levels, whereas postoperative reacquisition and reversal of the stem discrimination was not impaired (except following the combined NBM and MSA lesion). Lesions of the DGP had no effect on choice accuracy in any discrimination. When the discrimination on the arms was made more difficult by increasing the delay interval during which the information had to be remembered, rats with combined NBM and MSA lesions were again impaired relative to controls and showed no signs of recovery of function. These results provide information about the behavioral functions of the basal forebrain cholinergic system and suggest that pathological changes in certain components of this system can cause disorders of memory. PMID- 4038998 TI - The binding of peroxidase-labelled lectins to human breast epithelium. IV--The reactivity of breast carcinomas to peanut, soy bean and Dolichos biflorus agglutinins. AB - The binding of the lectins from peanut, soy bean and Dolichos biflorus (specific for galactose and/or N-acetyl-D-galactosamine), to human breast carcinomas has been investigated. In contrast to the consistent pattern found in normal breast the reactivity of carcinomas to peanut lectin is varied, the most striking differences being prominent binding without desialation in some tumours and virtual lack of reactivity in others. There tends to be a greater degree of binding of soy bean agglutinin to carcinomas than normal although this is not absolute, and the reverse applies to Dolichos biflorus agglutinin. Comparison of the binding of the three lectins has revealed a complex heterogeneity of the carbohydrate chains within individual tumours and between different carcinomas. A significant relationship between peanut lectin binding, with the use of neuraminidase, and tumour differentiation as been found, and to a lesser extent with soy bean agglutinin when desialation is performed. However, the pattern of reactivity of the carcinomas with these three lectins does not appear to be related to local lymph node metastasis. PMID- 4038999 TI - Aplastic anemia in Dubowitz syndrome. PMID- 4039000 TI - Hatching of northern fowl mite eggs held at different temperatures and humidities. PMID- 4039001 TI - Spontaneous endotoxinemia. PMID- 4039002 TI - Discriminative stimulus effects of morphine withdrawal in the dependent rat: suppression by opiate and nonopiate drugs. AB - Morphine-dependent rats can be trained to discriminate between s.c. injections of saline and 0.1 mg/kg of naltrexone. The discriminative effects of naltrexone, measured by the number of trials completed on the naltrexone-appropriate choice lever in a 20-trial avoidance paradigm, derive from stimuli associated with morphine withdrawal. Opiate and nonopiate drugs were injected s.c. and examined for their ability to block naltrexone-induced discriminative effects and loss of body weight in morphine-dependent rats. Seven opiates blocked dose dependently the discriminative effects of naltrexone and loss of body weight. Potency ranged from fentanyl (330 X morphine) to meperidine (less than 1 X morphine); effects were stereoselective for levorotatory isomers. Loperamide, an opiate that does not readily enter the brain, blocked loss of body weight but not discriminative effects, suggesting that discriminative effects are mediated centrally. Nonopiate behavioral depressants, diazepam, haloperidol and pentobarbital, did not substantially affect either dependent variable, but clonidine (0.01-1.0 mg/kg) blocked discriminative effects of naltrexone partially and weight loss completely. The blockade by morphine (30 mg/kg) of naltrexone-induced discriminative effects and weight loss was surmounted by increasing the dose of naltrexone whereas the blockade by clonidine (0.1 mg/kg) was not. Thus, blockade by opiates of effects of naltrexone appears to be due to a competitive interaction at the mu opioid receptor; clonidine has a different mechanism of action. This discrimination paradigm may afford a specific animal model for studying fundamental processes underlying physical dependence on opiates and for evaluating novel pharmacologic approaches for treating opiate withdrawal in humans. PMID- 4039003 TI - Dimercaprol in the treatment of thrombocytopenia purpura induced by gold salts. PMID- 4039004 TI - Homozygous familial hypercholesterolaemia with supravalvar aortic stenosis treated by surgery. PMID- 4039006 TI - Increased frequency of lymphocytic mitotic non-disjunction in recurrent spontaneous aborters. AB - Hypermodal chromosomal spreads occurred significantly more frequently in lymphocytes from couples with recurrent spontaneous abortion than from comparison populations. Previously, we reported a similarly increased frequency in couples with aneuploid offspring. Considering the frequency of aneuploidy among first trimester spontaneous abortions, we suggest that there may be a sub-population of persons predisposed to non-disjunction among couples with reproductive wastage. PMID- 4039005 TI - Investigation of human chromosome polymorphisms by scanning electron microscopy. AB - Human chromosome polymorphisms were investigated by scanning electron microscopy (SEM). Centromeric heterochromatin was of a constricted morphology. The extent of the C banded region was demarcated by a prominent circumferential groove in G banded chromosomes. Circumferential grooves were observed within the heterochromatin of chromosome 9, and the number of grooves present reflected the size of the region. Three dimensional viewing of satellites and short arms of acrocentric chromosomes, from different angles in the SEM, provided the opportunity for accurate assessment of the size of satellites to be made. Also, small morphological variations were defined in the SEM when definition was uncertain in the light microscope (LM). PMID- 4039007 TI - Chromatin-specific hypersensitive sites are assembled on a Xenopus histone gene injected into Xenopus oocytes. AB - A cloned histone H4 gene of Xenopus laevis is efficiently transcribed after injection into germinal vesicles of X. laevis oocytes. Deletion analyses indicate that less than 140 base-pairs of 5' flanking sequences and 50 base-pairs of 3' flanking sequences are required for efficient transcription of this gene in Xenopus oocytes. Chromatin footprint analysis by a direct end-label technique reveals discrete DNase I-hypersensitive and micrococcal nuclease-hypersensitive sites at the 5' and 3' boundaries of the gene, which bracket the transcribed region of this minichromosome. The specific chromatin structure assembled around this homologous gene, together with the finding that histone genes of Drosophila melanogaster are not assembled into specific nucleoprotein structures within Xenopus oocytes, strongly suggest that sequence-specific and species-specific factors may be responsible for generating the chromatin-specific hypersensitive sites at the boundaries of active genes. PMID- 4039008 TI - The tissue-specific chicken histone H5 gene is transcribed with fidelity in Xenopus laevis oocytes. AB - Vectors containing the chicken H5 gene were micro-injected into the nucleus of Xenopus laevis oocytes. Transcription of the H5 gene was accurately initiated and H5 transcripts with discrete 3' termini were produced. H5 transcripts were not polyadenylated in oocyte nuclei. PMID- 4039009 TI - The ontogeny of shell secretion in Terebratalia transversa (Brachiopoda, Articulata). I. Development of the mantle. AB - The morphology of the mantle in free-swimming and metamorphosing larvae of the articulate brachiopod Terebratalia transversa has been examined by scanning and transmission electron microscopy. The mantle begins to form approximately 2 days after fertilization and subsequently develops into a skirtlike lobe that encircles the middle region of the larval body. A simple epithelium covers both the outer surface of the mantle lobe and the inner side situated next to the pedicle lobe of the larva. During metamorphosis, the mantle lobe is everted over the anterior end of the larva. Thus, the epithelium covering the outer part of the mantle lobe in the larva subsequently becomes the inner epithelium of the juvenile mantle. Similarly, the inner epithelium of the larval mantle lobe represents the future outer epithelium of the juvenile mantle. In free-swimming larvae, the prospective outer mantle epithelium contains two types of cells, called "lobate" and "vesicular" cells. Lobate cells initially deposit a thin layer of amorphous material, and vesicular cells produce ovoid multigranular bodies. Following settlement at about 5 days postfertilization, the vesicular cells secrete an electron-dense sheet that constitutes the basal layer of the developing periostracum. Within several hours to a day thereafter, reversal of the mantle lobe is rapidly effected, apparently by contractions of the pedicle adjustor muscles. PMID- 4039010 TI - The ontogeny of shell secretion in Terebratalia transversa (Brachiopoda, Articulata). II. Formation of the protegulum and juvenile shell. AB - The fine structure of the shell and underlying mantle in young juveniles of the articulate brachiopod Terebratalia transversa has been examined by electron microscopy. The first shell produced by the mantle consists of a nonhinged protegulum that lacks concentric growth lines. The protegulum is secreted within a day after larval metamorphosis and typically measures 140-150 micron long. A thin organic periostracum constitutes the outer layer of the protegulum, and finely granular shell material occurs beneath the periostracum. Protegula resist digestion in sodium hypochlorite and are refractory to sectioning, suggesting that the subperiostracal portion of the primordial shell is mineralized. The juvenile shell at 4 days postmetamorphosis possesses incomplete sockets and rudimentary teeth that consist of nonfibrous material. The secondary layer occuring in the inner part of the juvenile shell contains imbricated fibers, whereas the outer portion of the shell comprises a bipartite periostracum and an underlying primary layer of nonfibrous shell. Deposition of the periostracum takes place within a slot that is situated between the so-called lobate and vesicular cells of the outer mantle lobe. Vesicular cells deposit the basal layer of the periostracum, while lobate cells contribute materials to the overlying periostracal superstructure. Cells with numerous tonofibrils and hemidesmosomes differentiate in the outer mantle epithelium at sites of muscle attachments, and unbranched punctae that surround mantle caeca develop throughout the subperiostracal portion of the shell. Three weeks after metamorphosis, the juvenile shell averages about 320 micron in length and is similar in ultrastructure to the shells secreted by adult articulates. PMID- 4039011 TI - Reports of the Judicial Council of the American Medical Association, December 1984. PMID- 4039012 TI - Progesterone as a predictor of cyclicity in Bolivian squirrel monkeys during the breeding season. AB - In a squirrel monkey breeding colony, two distinct groups of females were observed during the breeding season, December through March. One had low and the other had high estradiol (E2) and progesterone (P) concentrations. The conception rate in females with high E2 and P values was 74%. However, only 25% of monkeys with low steroid concentrations became pregnant during the breeding season. This study showed that all mature females in a colony may not be cycling concurrently and that two serum P measurements obtained at four-day intervals may be utilized to detect noncycling monkeys during the breeding season. PMID- 4039013 TI - Absence of therapeutic blood concentrations of tetracycline in rats after administration in drinking water. AB - Because of ease of administration and broad antibacterial spectrum, tetracycline often is administered in drinking water to control infectious diseases of rats. Assay of serum after a gavage bolus of tetracycline (300 mg/kg body weight) revealed little absorption of tetracycline by this route. Rats were given water containing tetracycline at several concentrations (400 mg/liter, 4g/liter, and 4 g tetracycline plus 50 g sucrose/liter) ad libitum and serum concentrations of tetracycline were monitored. Bioassay of serum samples from these animals, taken during 72 hours of water medication, revealed no detectable tetracycline concentrations (greater than 0.2 mcg/ml) in the 400 mg and 4 g/liter groups. Two of eighteen serum samples from the group given 4 g tetracycline with 50 g sucrose/liter had minimal therapeutic tetracycline concentrations (0.3 mcg/ml) effective for Mycoplasma pulmonis. Some of the animals given tetracycline ad libitum in drinking water drank very little and lost weight compared to control animals. These findings indicate that the practice of adding tetracycline to drinking water of rats may be ineffective in controlling systemic diseases, and also be detrimental to the treated animals. PMID- 4039014 TI - Cis-diamminedichloroplatinum (II)-induced acute renal failure in the rat. Correlation of structural and functional alterations. AB - Studies were undertaken to examine the relationship between renal morphologic and functional alterations during the development of cis-diamminedichloroplatinum (II) (CDDP)-induced acute renal failure (ARF). Control and CDDP-treated rats (10 mg/kg, intraperitoneally) were housed in metabolic cages for the purpose of renal function determinations. Renal morphology was studied by light and electron microscopy at 6, 24, 48, 72, and 96 hours following treatment. Six hours following CDDP administration, morphologic alterations consisting of nucleolar segregation, ribosome dispersion, and the formation of aggregates of smooth endoplasmic reticulum were observed throughout the P3 portion of the proximal tubule located in the outer stripe of the outer medulla and medullary rays. These changes became more frequently observed throughout P3 during the course of the study. At 24 and 48 hours, focal changes were also observed involving the P1 and P2 segments of the proximal tubule which make up the pars convoluta. ARF, indicated by a reduced creatinine clearance, was first apparent 48 hours following CDDP administration. The development of ARF was associated with focal, primarily sublethal, cell injury throughout the proximal tubule. By 72 and 96 hours necrosis primarily affecting P3 became widespread, and renal function progressively worsened. The establishment of ARF prior to the development of tubular necrosis suggests that the processes of tubular obstruction and/or tubular fluid backleak are not involved in the initiation of ARF in this model. Instead, the alterations involving P1 and P2 appear to be most important during the early stages of CDDP-induced ARF. The severity of the convoluted tubular injury at 48 hours showed a significant correlation with the degree of renal function impairment. The tubular injury affecting P3 did not correlate with the loss of renal function at any of the time points studied. However, tubular injury in P3 did appear responsible for some degree of renal function impairment at 72 and 96 hours, probably as a result of tubular obstruction and/or tubular fluid backleak. PMID- 4039015 TI - Metastasis in the androgen-insensitive Nb rat prostatic carcinoma system. AB - This unit has in the past evaluated the Nb rat prostatic adenocarcinoma model with respect to chemotherapies. Recently, this unit has been evaluating agents that may have a role in decreasing metastatic rate. The three androgen insensitive tumors, Nb Pr A.I. I, II, III, have been evaluated herein. Agents that have been used include indomethacin, heparin, heparin plus cortisone, and heparan sulfate (SP54). It has been shown that these agents do play a role in reducing the metastasis. In evaluation of Nb Pr A.I, I, control animals had a metastatic rate of 57%. In treatment with indocin, only 21% of the animals, three of 14 animals treated, had a metastasis, and treatment with heparin and cortisone resulted in one of 14 animals having metastasis. Similar observations were seen when treatment with SP54 and heparin was evaluated in the Nb Pr A.I. III; 18 and 27% of treatment group animals had metastasis, whereas 55% of control groups had metastasis. Similarly, in the Nb Pr A.I. II evaluation, control animals having a metastatic rate of 43% had heparin plus cortisone and heparin alone, and this particular tumor model revealed complete resolution with no animals having metastatic disease. The majority of these agents have not effected tumor volume in terms of reduction as much as the best chemotherapeutic agents in this model system include cyclophosphamide and cis-platinum. PMID- 4039016 TI - Use of gut cyclic motor activity to evaluate a stimulant (narcotic) and inhibitor (anticholinergic) of gastrointestinal-tract activity in the unanesthetized dog. AB - The use of gut cyclic motor activity to evaluate both a stimulant and inhibitor of gastrointestinal contractile activity in the unanesthetized dog is described. In the interdigestive (fasted) state, there is a cyclic alternation of intense periods of contractions (burst) with quiescent periods (basal). Codeine phosphate, a narcotic agent, caused a dose-dependent increase in the number and duration of circular muscle contractions when administered in the basal phase. Hyoscine N-butyl-bromide, an anticholinergic drug, caused a dose-dependent reduction in both amplitude and frequency of burst-phase contractions. When a combination of codeine phosphate and hyoscine N-butylbromide was administered simultaneously in the basal or burst phase, the hyoscine N-butylbromide prevailed and had the dominant effect. This is a useful in vivo model to evaluate the effects of drugs on the gastrointestinal tract. PMID- 4039017 TI - Prostaglandin E1. A new therapy for refractory right heart failure and pulmonary hypertension after mitral valve replacement. AB - Patients undergoing mitral valve replacement, particularly those with severe pulmonary hypertension and/or congestive heart failure, may develop life threatening right heart failure in the immediate postbypass period. We have observed that such patients have intense pulmonary vasoconstriction. The markedly increased pulmonary impedance may aggravate the right heart failure and prevent recovery of right ventricular function in this setting. Therefore, we studied the effects of high-dose prostaglandin E1 (30 to 150 ng/kg/min), a potent pulmonary vasodilator, in combination with massive infusion of norepinephrine (up to 1 microgram/kg/min) into the left atrium in five consecutive patients with refractory right heart failure and pulmonary hypertension after mitral valve replacement. This pharmacologic approach takes advantage of the pulmonary vasodilating effects of prostaglandin E1, while offsetting associated systemic vasodilation and resulting hypotension. All five patients had rapid pulmonary vasodilator responses followed by marked improvement in right ventricular function. All survived the operation and none had right ventricular infarction or chronic right heart failure postoperatively. PMID- 4039018 TI - Orally administered specific transfer factor for the treatment of herpes infections. PMID- 4039019 TI - [Intense thrombocytopenia associated with the use of heroin]. PMID- 4039020 TI - Otitis media with effusion in preschool children. AB - The incidence, prevalence, and natural history of otitis media with effusion (OME) and middle ear high negative pressure (HNP) were investigated in a group of 2 to 6 year old preschool children. The children were examined monthly over a two year period from September 1981 to August 1983. The middle ear status was assessed using a decision-tree algorithm which combined the findings of pneumatic otoscopy, tympanometry, and acoustic reflex measurements. Fifty-three percent of the children in the first year and 61% in the second year developed OME; also during the two years, HNP was documented in 66% of the children. Eighty percent of OME episodes lasted only two months. The prevalence of OME and HNP showed a seasonal variation and a strong association with the presence of upper respiratory infections (URIs). The incidence of OME was independent of age. These data indicate that OME and HNP are prevalent conditions with a high spontaneous recovery in the preschool population. PMID- 4039021 TI - X-linked mixed hearing loss: four case studies. AB - To present four cases of an X-linked inner ear malformation, the authors studied inner ear malformations and present here all the radiological, genetic, and audiological tests of these patients. The importance of this paper is to reinforce the differential diagnosis between this pathology and otosclerosis in order to avoid surgical procedures. PMID- 4039022 TI - Argon laser coagulation of blood for the anastomosis of small vessels. AB - A new technique is introduced in which an argon laser coagulates blood to form an adherent sleeve for the anastomosis of small vessels. The argon laser solidifies the blood into a dark tensile substance which supports the site of repair until vascular continuity is achieved. Laser pulses of 0.75 W and 0.5 seconds exposure are used, and damage to the underlying vessel wall is minimal. A histological analysis is performed and the results are examined qualitatively. The technique shows advantages of speed, reduced vascular trauma, and external protection at the site of vascular repair. PMID- 4039023 TI - Withdrawal syndrome follows abrupt cessation of intracerebroventricular infusion of epinephrine in spontaneously hypertensive rats. AB - Aortic blood pressure and heart rate were measured directly during chronic (5 day) intracerebroventricular infusion of epinephrine in conscious, unrestrained spontaneously hypertensive rats (SHR), and following abrupt cessation of drug infusion. During the infusion period, no statistically significant differences in mean aortic pressures were observed between SHR that received vehicle and those which received epinephrine at 1.25, 2.5, or 5.0 micrograms (base) per hour for 5 days via osmotic minipumps. A significant reduction in heart rate was noted during some, but not all, days of the epinephrine infusion period; the onset of bradycardia appeared to be dose-related. Immediately following abrupt cessation of epinephrine (but not vehicle) infusion, a complex withdrawal syndrome was observed to include: a significant and sustained elevation of aortic blood pressure, tachycardia, increased water consumption, and several distinct behavioral effects. The reaction appeared maximal at about 2 hours, and lasted less than 24 hours. PMID- 4039024 TI - Ethanol directly increases dihydrotestosterone conversion primarily to 5 alpha androstan-3 beta, 17 beta-diol in rat Leydig cells. AB - Our studies demonstrate that direct stimulation of dihydrotestosterone metabolism by ethanol (2.2 - 65 mM) in rat Leydig cells primarily involves an increase in 5 alpha-androstan-3 beta, 17 beta-diol. Although the enzyme catalyzing this conversion, 5 alpha-androstane-3 beta-hydroxysteroid dehydrogenase, is localized in the microsomal fraction of Leydig cells, ethanol does not increase 5 alpha androstan-3 beta, 17 beta-diol formation in isolated microsomes, presumably because of the removal of soluble alcohol dehydrogenase activity, which we propose mediates this action. Because 5 alpha-androstan-3 beta, 17 beta-diol is generally considered a weak or inactive androgen, this effect may function to decrease dihydrotestosterone secretion by Leydig cells and/or to reduce the availability of this androgen in responsive tissues. PMID- 4039025 TI - Cyclosporine alters opiate withdrawal in rodents. AB - Opiates exert numerous effects on all levels of the central nervous system with tolerance, physical dependence and withdrawal being characteristics of this drug class. The degree of dependence is directly correlated to the intensity of withdrawal. Therefore, success in modifying the withdrawal syndrome may shed light on the dynamics of opiate addiction. The present study demonstrates that cyclosporine, a widely used immunosuppressive drug, considerably modified the behavioral signs of a naloxone-induced abstinence syndrome in morphine-addicted rats. In previous experiments, alpha-interferon has shown similar results. The similarity in actions of these two immunomodulator drugs is discussed and we suggest that opiate addiction may involve the immune system. PMID- 4039026 TI - Vindesine and high-dose cisplatin in the treatment of advanced non-small-cell lung cancer. AB - Seventeen patients with advanced non-small-cell lung cancer (NSCLC) were entered on a combination chemotherapy protocol including vindesine and high-dose cisplatin. All patients had measurable disease and had not previously received chemotherapy. All patients entered were evaluable for toxicity and response. Tumor regression was limited to one complete and one partial response (response rate, 11.7%; 95% confidence limits, 0 to 27%). The complete and partial response lasted 260 + and 82 days, respectively. For the 15 nonresponding patients, the median time to disease progression was 76 days. Median survival was 141 days for the whole group. Significant toxic effects were vindesine-related peripheral neuropathy and cisplatin-induced emesis. Myelosuppression was mild and manageable. The response for the vindesine-cisplatin combination observed in our study is inferior to that seen in a previous vindesine-cisplatin trial reported by others. Thus, the true value of this two-drug regimen in the treatment of NSCLC remains to be established. PMID- 4039027 TI - [Acute gastric ulcerations in rats with obstructive jaundice--with special reference to gastric mucosal blood flow]. AB - The mechanism of acute gastric ulcerations in rats with obstructive jaundice was investigated in terms of the changes in the gastric mucosal blood flow. Further, the effect of vagotomy with or without obstructive jaundice was examined. One hundred and eighty-eight Sprague-Dawley rats weighing about 250 g were prepared and divided into 4 groups as follows; sham operation (control group), ligation of the bile duct (jaundiced group), vagotomy with pyloroplasty (vagotomized group), ligation of the bile duct and vagotomy with pyloroplasty (jaundiced and vagotomized group). After two weeks, water immersion and restraint stress procedures were performed in these 4 groups. The gravity of the gastric ulcerations was calculated by ulcer index. The gastric mucosal blood flow was measured by hydrogen clearance technique. The following results were obtained. The control group showed increased ulcer index and decreased gastric mucosal blood flow after the stress procedures. The jaundiced group showed significantly higher ulcer index and early, significant decrease of gastric mucosal blood flow compared to the control group after the stress procedures. The vagotomized group showed significantly decreased ulcer index after stress procedures compared to the control group, however, the gastric mucosal blood flow were unchanged between both groups before and after the stress procedures. The jaundiced and vagotomized group showed significant decrease of ulcer index and improvement of decrease of gastric mucosal blood flow compared to the jaundiced group. These data suggested that the significant decrease of gastric mucosal blood flow during the stress procedures was one of exacerbating factors of the acute gastric ulcerations in rats with obstructive jaundice, and vagotomy might prevent them by maintaining the gastric mucosal blood flow in obstructive jaundice. PMID- 4039028 TI - Activation of the c-abl oncogene by viral transduction or chromosomal translocation generates altered c-abl proteins with similar in vitro kinase properties. AB - The v-abl protein of Abelson murine leukemia virus is a tyrosine-specific kinase. Its normal cellular homolog, murine c-abl, does not possess detectable tyrosine kinase activity in vitro. Previously, we have detected tyrosine kinase activity in vitro for an altered c-abl gene product (c-abl P210) in the K562 human chronic myelogenous leukemia cell line. The expression of this variant c-abl gene product correlates with chromosomal translocation and amplification of the c-abl gene in K562 cells. Like v-abl, c-abl P210 is a fusion protein containing non-abl sequences near the amino terminus of c-abl. We compared the in vitro tyrosine kinase activity of c-abl P210 with that of wild-type murine v-abl. The remarkable similarities of these two proteins with respect to cis-acting autophosphorylation, trans-acting phosphorylation of exogenous substrates, and kinase inhibition, using site-directed abl-specific antisera, suggested that c abl P210 could function similarly to v-abl in vivo. In addition, c-abl P210 possessed an associated serine kinase activity in immunoprecipitates. The serine kinase activity was not inhibited by site-directed, abl-specific antisera that inhibit the tyrosine kinase activity, suggesting that the serine kinase activity is not an intrinsic property of c-abl P210. Thus, the activation of the c-abl gene in a human leukemia cell line may have functional consequences analogous to activation of the c-abl gene in Abelson murine leukemia virus. PMID- 4039029 TI - [Follow-up study of former prenatally dystrophic newborn infants now 6 to 12 years old]. AB - 58 small-for-date (SFD) aged 6 to 12 years, born between 1970 and 1975 were followed-up. Retardation of motor skills and speech during early infancy was found in 20-30%. At 6 to 12 years of age one third still had deficits in body weight und height. Neurological abnormalities in 17 children were usually mild, most often affecting fine motor function. Significant impairment of visuomotor perception on psychological testing was seen in 21 children, and EEG abnormalities in 20 cases. The results in neurological, psychological and EEG investigations for 23 children (group I) were normal. 24 patients (group II) showed one or two abnormal findings. In 9 children (group III) results of all three examinations were abnormal. The follow-up results were influenced by socioeconomic factors. Small-for-date babies showed on the whole encouraging results on follow-up during later childhood, with 40% of the children being normal, and mostly mild abnormalities in the remaining patients. Prognosis may be further improved by preterm delivery, i.e. early termination of intrauterine growth retardation. PMID- 4039030 TI - The differential effect of benzamide upon the toxicity and mutations produced in Chinese hamster ovary cells by N-methyl nitrosourea, N-ethyl nitrosourea and N hydroxy-2-aminofluorene. PMID- 4039031 TI - X-ray sensitive mutants of Chinese hamster ovary cell line: radio-sensitivity of DNA synthesis. AB - 6 mutants of the CHO cell line hypersensitive to ionizing radiation have been previously described (Jeggo et al., 1982; Jeggo and Kemp, 1983). In this report, the degree of radiosensitivity of DNA synthesis in these mutant strains has been investigated. 5 of the 6 mutant strains showed a greater degree of inhibition of DNA synthesis following gamma-irradiation compared to the wild-type strains, one mutant showed a similar response to the parent strain. An analysis of the size of the DNA made after irradiation in mutant and wild-type strains indicated that initiation events were more inhibited than chain elongations. This enhanced radiosensitivity is in contrast to results observed using ataxia telangiectasia fibroblasts, in which DNA synthesis is radioresistant in comparison to normal skin fibroblasts. These results are interpreted on the basis of sensitivity resulting from a defect in DNA repair in these mutant strains. PMID- 4039032 TI - Double-strand break repair and G2 block in Chinese hamster ovary cells and their radiosensitive mutants. AB - Two X-ray-sensitive mutants of the CHO K1 cell line were examined for their cell cycle progression after irradiation with gamma-rays, and for their ability to rejoin double-strand breaks (DSBs) as detected by neutral filter elution. Both mutants were impaired in DSB rejoining and both were irreversibly blocked in the G2 phase of the cell cycle as determined by cytofluorometry. From one mutant we have isolated several revertants. The revertants stem from genomic DNA transfection experiments and may have been caused by gene uptake. All revertants survived gamma-irradiation as did the wild-type CHO line. One of them has been examined for its ability to rejoin DSBs and was found to be similar to the wild type. PMID- 4039033 TI - Co-recessive inheritance: a model for DNA repair, genetic disease and carcinogenesis. AB - A genetic model for some cases of excision-deficient xeroderma pigmentosum (XP) is proposed in which the trait (i.e., XP) is expressed if and only if the individual is homozygous or hemizygous for defective alleles at more than one of a specific set of loci. The model might also apply in some cases of certain other diseases associated with defective DNA repair. The model accounts for several paradoxical aspects of XP, including the large number of complementation groups despite the biochemically limited DNA-repair defect, the co-existence of XP and Cockayne's syndrome in two different complementation groups of XP, siblings with markedly different degrees of severity of XP in one family and transmission of the disease in an X-linked manner in another, the existence of some individuals who appear to have the DNA-repair defect but not clinical XP, and the seeming paradox of a disease associated with a marked defect in a DNA-repair mechanism but not associated with an obvious increase in incidence of internal cancer. The model predicts that a large proportion of the general population is a carrier of one or more of these defective genes for DNA-repair mechanisms. Such genes may be important in the etiology of much of human cancer. PMID- 4039034 TI - The spiral organ of dermatophytes. PMID- 4039035 TI - Successful treatment of amegakaryocytic thrombocytopenic purpura with cyclosporine. PMID- 4039036 TI - An antibody cytotoxic to megakaryocyte progenitor cells in a patient with immune thrombocytopenic purpura. PMID- 4039037 TI - Somatomedin C in rheumatoid arthritis. PMID- 4039038 TI - Lymphocyte development genes and immunodeficiency disease. PMID- 4039040 TI - The antitumor activity of oxoplatinum. AB - A coordination complex cis-dichlorodiamminedihydroxoplatinum (IV) (oxoplatinum) was first synthesized in the USSR by Chugaev and Khlopin in 1927 [3]. Its marked antitumor properties were revealed by one of the authors of this article at the All-Union Cancer Research Center of the Academy of Medical Sciences of the USSR. The paper gives data on the antiblastic and side effects of oxoplatinum and also on the results of pharmacokinetic studies of the drug. Particular attention was paid to the similarity and differences of biological properties of oxoplatinum and cis-dichlorodiammineplatinum(II) (DDP) which has found wide use in oncological practice. It has been established that, on principle, oxoplatinum differs from DDP in action on the body and tumors. The new drug is 10 times less toxic than DDP. Oxoplatinum has a wide spectrum of antineoplastic action resulting in marked inhibition of growth of solid and ascitic forms of transplantable tumors. The drug has a longer duration of antitumor effect after the end of the therapeutic course. An important property of oxoplatinum is its high therapeutic index. The new drug manifests high antitumor activity with different ways of its administration into the body. Oxoplatinum in therapeutic doses does not produce necrotic lesions in the kidneys. The new drug exerted no cross-resistance with DDP and the alkylating antitumor agent sarcolysin. At the present time oxoplatinum is undergoing preclinical investigation. PMID- 4039039 TI - Diacylglycerol in large alpha-actinin/actin complexes and in the cytoskeleton of activated platelets. AB - The interaction of the cytoskeleton with plasma membranes may be mediated by vinculin, alpha-actinin and other proteins; alpha-actinin can interact specifically with model membranes only if they contain diacylglycerol and palmitic acid. On stimulation of platelets by thrombin, which leads to a reorganization of the cytoskeleton, diacylglycerol is produced rapidly, simultaneously with the disappearance of phosphatidylinositol. One important function of the diacylglycerol produced in platelets may be the activation of the Ca2+-and phospholipid-dependent protein kinase C. We show here that, in the presence of diacylglycerol and palmitic acid, a supramolecular complex between alpha-actinin and actin is formed in vitro. In the electron microscope, this complex displays substructures similar to those of microfilament bundles in vivo. Furthermore, such alpha-actinin/lipid complexes can also be formed in situ during the stimulation of blood platelet aggregation. Thus, alpha-actinin may be one of the proteins directly involved in structures connecting the cytoskeleton to cell membranes. PMID- 4039041 TI - Ethanol and brain protein synthesis in the rat in vivo. AB - The effect of ethanol consumption (27% of calories) for 21 days, concomitant with a low-protein (6% calories) or a normal protein diet (17.5% calories), on tyrosine kinetics and protein synthesis in the brain, was investigated. Ethanol consumption did not affect tyrosine concentrations in the plasma, cerebellum, forebrain or olfactory bulb but increased significantly the rate of synthesis of total mixed protein in the forebrain and cerebellum. This effect was observed in rats fed on both dietary protein regimes. PMID- 4039042 TI - Recognition and treatment of premenstrual syndrome. AB - Premenstrual syndrome (PMS) is the title applied to a broad range of physical and psychological symptoms that occur cyclically, usually seven to 14 days prior to the onset of a woman's menstruation, and disappear during menstruation. Although the symptoms of premenstrual syndrome were described more than 50 years ago, recognition of PMS by the medical establishment as a discrete condition, which requires attention and treatment, is a fairly recent development. It is estimated that 30 percent of women experience PMS in a debilitating form at some point in their lifetimes from menarche to menopause. The symptomatology of PMS is varied; it includes such psychological symptoms as irritability, depression, oversensitivity, mood swings and anxiety, in addition to such physical symptoms as water retention, breast tenderness, weight gain and migraines. This broad range of symptoms has increased the difficulty of establishing an etiology for the syndrome, and it is now suggested that there may be several processes at work, each responsible for a different aspect of PMS. Care of the PMS patient by nurse practitioners initially requires acknowledgment of the legitimacy of her condition. A detailed physical examination should be accompanied by careful interviewing to elicit the most complete picture of the patient's experience with PMS. Treatment, which can involve dietary changes, hormone or antigonadotropin administration, must be individualized according to a patient's initial symptomatology and subsequent response. At present, research is in progress which will enhance our understanding and ability to deal with PMS. PMID- 4039044 TI - Evaluating premenstrual symptoms in medical practice. AB - Essential diagnostic criteria for evaluating premenstrual syndrome (PMS) symptoms are marked change in intensity of symptoms measured on postmenstrual and premenstrual days and documentation of changes for at least two cycles. Four symptom evaluation methods in a PMS treatment program are compared and discussed: physician interview, menstrual symptom questionnaire, daily symptom ratings, and the Hopkins symptom checklist. Data from 241 patients who met the criteria for marked change in symptoms show that premenstrual symptom levels are severe, a subgroup has moderate symptoms continuing in the follicular phase, and that emotional symptoms are predominant. Diagnostic evaluation needs to distinguish menstrually related disorder from undiagnosed physical or psychiatric illness. Further research is needed to identify a classification system of multiple subtypes of menstrual disorders. PMID- 4039043 TI - Correlation of ominous fetal heart rate patterns and brain-specific creatine kinase. AB - Creatine kinase isoenzyme analysis was performed on the cord blood of 125 infants who had undergone at least 30 minutes of intrapartum electronic fetal monitoring. The tracings were scored blindly according to severity of abnormal patterns, and the infants were grouped into ominous, intermediate, and normal scores. No differences were seen in creatine kinase MM or creatine kinase MB levels among the three groups. However, infants with ominous fetal heart rate patterns had higher creatine kinase BB levels and poorer outcome than infants with normal patterns. PMID- 4039045 TI - Anicteric presentation of fatal herpetic hepatitis in pregnancy. AB - Herpes simplex virus hepatitis in pregnancy was first reported in 1969. Seven other cases have since been reported, and this communication describes two additional cases. The clinical presentation and laboratory profiles of these two cases parallel those described. Unreported, however, is the sharp contrast between the presentation of pregnant patients with herpes simplex virus hepatitis and the presentation of pregnant patients with other life-threatening forms of hepatitis. Nine of ten patients reported to date have been anicteric with peak total bilirubin levels of less than 1.3 mg/dL before cesarean section or laparotomy. That this presentation may not be unique to pregnancy is suggested by three case reports of fatal, anicteric herpes simplex virus hepatitis in previously healthy, nonpregnant adults. The cause of this phenomenon is unknown. PMID- 4039046 TI - Hyperprolactinemia and associated pituitary prolactinomas. AB - The association between serum prolactin (PRL) and the presence of pituitary tumors as determined by third generation computed tomography scan was studied in hyperprolactinemic patients. Patient charts from a four-year period were reviewed to identify those patients with elevated PRL (greater than or equal to 25 ng/mL). All patients with hyperprolactinemia underwent computed tomography scan evaluation of the pituitary gland. Hyperprolactinemia was identified in 79 patients, mean PRL 59 +/- 6.1 ng/mL SEM. Pituitary tumors were identified in 35 of these patients, mean PRL 65 +/- 11.9 ng/mL. This level was not significantly different from the level in 43 patients with normal computed tomography scans (52 +/- 5.7 ng/mL). This review found that computed tomography scan identified pituitary tumors in 44% (35 of 79) of patients with hyperprolactinemia. The likelihood of finding a pituitary tumor did not correlate with the level of hyperprolactinemia. Computed tomography scan is indicated for the diagnosis of prolactinomas in all hyperprolactinemic patients regardless of the serum PRL level. PMID- 4039048 TI - Umbilical cord prolapse. PMID- 4039047 TI - Case-control study of galactorrhea and its relationship to the use of oral contraceptives. AB - A case-control study was performed to determine the relationship between galactorrhea and the use of oral contraceptives as well as other risk factors. The cases included all 109 Olmsted County residents who satisfied the diagnostic criteria for galactorrhea between 1970 and 1980. Control subjects were selected from a sampling frame of all medical registrations and matched to the cases by age, year, and residency. Pituitary adenomas were strongly associated with galactorrhea, as the relative risk was 23.2 (95% confidence interval 2.0 to 90.0). In galactorrhea cases without pituitary adenomas there was an association with oral contraceptives (ever use versus never use), as the relative risk was 2.3 (95% confidence interval 1.3 to 4.4). Among current users of oral contraceptives, the risk of galactorrhea was not increased, but there was a trend of diminishing risk with duration of use. The estimate of relative risk was 3.1 after discontinuation of oral contraceptive use and was highest for the first year after discontinuation (5.5), compared with a year or more after discontinuation (2.1). Thus, galactorrhea was associated with the cessation of oral contraceptives. PMID- 4039049 TI - Cardiac surgery review--by peers or by state? PMID- 4039050 TI - [Dynamics of perinatal and infant mortality]. PMID- 4039051 TI - Autotomy following limb denervation: effects of previous exposure to neurectomy. AB - Neurectomy, dorsal rhizotomy or spinal cord lesions can evoke self-attack and autotomy of portions of insensate limbs. This behavior has been attributed to dysesthesia and/or pain. However, the majority of animals subjected to these lesions do not exhibit self-mutilation. This study was designed to test for individual predisposition to self-mutilative behaviors by effecting two sequential limb denervations. In susceptible animals, denervation of the first limb induced circulatory, trophic and inflammatory reactions and/or autotomy. Inflammation developed slowly in one or two digits of some animals and then spontaneously resolved. Other animals attacked the tips of inflamed digits effecting local autotomy. Still other animals aggressively attacked multiple digits, rapidly developed diffuse inflammation and produced extensive autotomy. Denervation of a second limb, following complete healing of all tissue injury, induced by the first denervation, produced several dramatic responses. Nearly 90% of those responding with autotomy to the first denervation responded with autotomy to the second denervation. In contrast, only 11% of the non-attackers showed autotomy following the second denervation. The inflammatory and autotomy responses to the second denervation were markedly reduced in latency and increased in intensity. The pattern of autotomy was stereotyped, initiated at the digit tips, progressed proximally, lead by advancing inflammation. It is suggested that a strong host-response component is involved in the autotomy response. PMID- 4039052 TI - Autotomy following limb denervation: effects of sparing selected afferents. AB - Lesions of the brachial plexus are often followed by inflammation, self-inflicted scratching and autotomy of the denervated extremity. If innervation of the shoulder girdle muscles was spared, this denervation syndrome was decreased in incidence and intensity as compared to a full brachial plexus section. Spared innervation increased the latency between the appearance of inflammation and autotomy, revealing a strong linkage between the site of inflammation and the site of autotomy attack. Plexus lesions, which spared one of the nerves of the distal limb, also decreased the incidence and intensity of autotomy and shifted self-attack from autotomy to scratching wounds. Subsequent section of this nerve produced a two-stage brachial plexus denervation, and the cumulated autotomy was markedly less than that produced by a single-stage brachial plexus denervation. Scratching wounds and autotomy exhibited similar latencies. Scratching was directed towards areas of partial innervation and autotomy towards areas of total denervation. The results are discussed in terms of the possible contributions of dysesthesia inflammation and ischemia in scratching behavior and autotomy. PMID- 4039053 TI - A study of low socioeconomic status, black teenage fathers and their nonfather peers. AB - Demographic background, attitude and knowledge about pregnancy and contraception, and family characteristics and dynamics of 100 teenage fathers were studied and compared with those of 100 nonfather, age-matched peers. The subjects' age ranged from 14 to 19 years with a mean age of 17.5 years. Nearly all subjects were black and were from families of low socioeconomic status. There were no differences between the two groups for age at first sexual intercourse (mean 12.5 years) and frequency of intercourse in the last year. More control subjects than fathers perceived pregnancy as disruptive of their future plans for school, job, and marriage. Teenage fathers were more likely to have mothers who were teenage parents (77% v 53%, P = .0007). In both groups, one third of their brothers and 44% of their sisters were teenage parents. Both groups had poor knowledge about the risk of pregnancy and the effectiveness of contraceptives. In both groups, negative attitudes about contraceptives represent barriers to their use. Both groups of subjects became sexually active at young ages, had poor knowledge about pregnancy prevention, and often had unprotected intercourse. Although there were many similarities between the two groups, the teenage fathers, in particular, seemed to come from an environment in which teenage pregnancy was common, accepted, and perceived to be minimally disruptive of their lives now or in the future. PMID- 4039054 TI - An autosomal recessive bone dysplasia syndrome resembling hypochondroplasia. PMID- 4039055 TI - Behavioral analysis of sexual dysfunction in Hansen's disease. AB - Human sexual behavior is an interactive process including CNS, hormonal, and sex gland activities. This process can be disrupted in males who have Hansen's disease if testicular atrophy occurs. Elevations of centrally mediated luteinizing hormone and deficient testosterone levels were found in a male with Hansen's disease whose insufficient erections were secondary to atrophic testes. Quasi-experimental (A-B) analysis provided evidence for the efficacy of testosterone treatment for such a condition. PMID- 4039056 TI - Adenocarcinoma of the colon with syncytiotrophoblastic differentiation: differential diagnosis and implications. AB - A case of adenocarcinoma of the colon is reported, whose metastases exhibited a syncytiotrophoblastic differentiation that gradually increased with advancing distance from the primary. Immunohistochemically, syncytiotrophoblastic giant cells with strong positivity for beta-HCG could be demonstrated within the metastatic tissue. Also, there was beta-HCG positivity in a fraction of the atypical epithelial elements of the primary. The case is discussed with respect to the differential diagnosis, and the cause of the syncytiotrophoblastic differentiation is attributed to the phenomenon of genetic instability. The case shows that by virtue of genetic instability totally new differentiations may be elaborated, so that the phenotypical appearance of a given tumor does not necessarily allow conclusions as to its tissue of origin. Thus, observations such as the one presented here clearly indicate that the histogenetic principle of tumor classifications by far does not apply to all cancers and that, therefore, its value and validity are considerably limited. PMID- 4039057 TI - Identical twins with uterus didelphys and duplex kidneys. PMID- 4039058 TI - Cardiac imaging techniques in the diagnosis of angiosarcoma of the heart: report of two cases. AB - Angiosarcoma of the heart is a rare and highly malignant tumour. Most of the reported cases have been diagnosed post mortem. In a one year period two cases were diagnosed during life and surgically treated. The only possible hope for survival is early diagnosis and surgical removal. Our cases illustrate the contribution of cardiac imaging techniques to early diagnosis and the feasibility of radical excision of this tumour. PMID- 4039059 TI - [Dyssegmental dysplasia. Clinical case report and review of literature]. PMID- 4039060 TI - [Determination of phospholipase A2 and lysophospholipase A1 in a mixture]. AB - The phospholipase A2 and lysophospholipase A1 activities were determined in various mixtures. When estimating the phospholipase A2 activity in venoms of snakes and insects the known methods based on measuring a change in the optical density of the egg yolk suspension are not acceptible if in investigated object besides phospholipases lysophospholipases are present (venoms of viper and giant hornet). In this case anomalous curves of changes in the system optical density in time are obtained. At the same time the analysis of such curves revealed that the method can be rather sensitive for determining lysophospholipases in venoms, as well as in phospholipase preparations of different purification, including electrophoretically homogeneous preparations. The results obtained enabled us to estimate the content of phospholipase A2 and lysophospholipase A1 in the venom of giant hornet and in its fractions, obtained during isolation and purification of the concerned enzymes. PMID- 4039061 TI - [Case of galactorrhea in a transsexual male patient]. PMID- 4039062 TI - [Circadian rhythm of corticosteroids in female hamadryas baboons during long-term hypokinesia]. AB - Radioimmunoassay was used to study the effect of restricted motor activity on the circadian rhythms of the content of hydrocortisone, 11-deoxycortisol, corticosterone and aldosterone in the blood plasma of mature female hamadryas baboons in different phases of the menstrual cycle. Intact animals demonstrated distinct circadian rhythms of corticosteroids reproduced stably in both phases of the cycle. Two-week immobilization did not change the general nature of rhythms of the content of glucocorticoids but caused a decrease in their mean daily concentrations which is significant for 11-deoxycortisol and corticosterone of female baboons immobilized in the luteal phase of the cycle. The circadian rhythm of aldosterone got smooth, its level in the blood dropped significantly disregarding a cycle phase at the moment of immobilization. The revealed changes of the circadian rhythms of aldosterone reflect disorders of adrenocortical mineralocorticoid function in female baboons under hypokinesia. Causes of changes in the hormonal activity of the adrenal cortex under clinicostatic hypokinesia are discussed. PMID- 4039063 TI - Carcinoma of the pancreas. PMID- 4039064 TI - New plants and plant products as food. PMID- 4039065 TI - Role of natriuretic factor in central nervous system (CNS)-induced natriuresis. AB - The presence of a natriuretic factor in the plasma of rats in which a 350 mM Na (high Na) artificial cerebrospinal fluid (CSF) was infused into the lateral ventricle was tested. Blood was obtained from control rats and rats which received an infusion of high Na CSF intraventricular (IVT) for 15 min. The plasma was incubated for 30 min at room temperature, acidified, placed in a boiling water bath, and then centrifuged. The plasma supernate was assayed for natriuretic activity in pentobarbital anesthetized bioassay rats. Sodium excretion increased 6.5 +/- 1.1 mueq/kg X min in rats which received an infusion of a control saline solution, 13.3 +/- 3.2 mueq/kg X min in rats which received infusion of control plasma supernates, and 32.1 +/- 8.3 mueq/kg X min in those rats which received plasma supernates from rats infused with high Na CSF IVT. Blood pressure was unchanged in all groups. The increment in sodium excretion elicited by plasma supernate from the high Na IVT group was significantly greater than that elicited by either control saline solution or control plasma extracts. Therefore, it is concluded that a heat-stable and nonpressor natriuretic factor is present in the plasma of rats infused IVT with high Na CSF. PMID- 4039066 TI - Neonatal herpes simplex: a worldwide disease which is potentially preventable and treatable. PMID- 4039067 TI - Hyperthermia in the rat from handling stress blocked by naltrexone injected into the preoptic-anterior hypothalamus. AB - Experimental handling and colonic temperature measurement have been shown to cause stress and induce a long-lasting rise in colonic temperature in the rat. This stress-induced hyperthermia was blocked by microinjection of the narcotic antagonist naltrexone into the preoptic-anterior hypothalamus (POAH) of the brain, but was not significantly affected by similar injections into areas of the brain above the POAH. Thus, the stress-induced hyperthermia may be caused by activation of the endogenous opioid mechanism in the POAH. PMID- 4039068 TI - The incidence of experimental contracture varies with the source of the prosthesis. AB - Nominally equivalent gel-filled miniprostheses supplied by three different manufacturers were placed subcutaneously in rats under identical conditions in a double-blind comparison. The incidence of experimental contracture, defined by grossly visibly asymmetrical distortion of the implant, was 0, 9, and 91 percent for the different manufacturers, consistent with previous observations. Differences among the different implants with respect to the density of the fibrillar capsule structure, the cellularity, and the amount of extruded gel did not correlate with the incidence of contracture. Contracture rate was inversely proportional to the relative degree of filling of the prostheses, as reflected in deviations from the nominal hemispherical shape, and to the viscosity of the gel filling. For implants of the same type, the incidence of contracture was higher when the prosthesis was underfilled. Contracted capsules were more fibrous and contained more cells with microfilament bundles. It is concluded that the physical and geometric properties of silicone implants are critical in the expression of contracture and that these properties vary significantly among prosthesis manufacturers. PMID- 4039069 TI - Differential effect of alcohol on aggressive behavior in dominant and subordinate hamsters. PMID- 4039070 TI - Effect of heat shock on the intracellular distribution of proteins. AB - Exposure of cells to heat induces thermotolerance, a transient resistance to subsequent heat challenges. It has been shown that thermotolerance is correlated in time with the enhanced synthesis of heat shock proteins. In this study, the association of induced heat shock proteins with various cellular fractions was investigated and the heat-induced changes in skeletal protein composition in thermotolerant and control cells was compared. All three major heat shock proteins induced in Chinese hamster fibroblasts after a 46 degrees C, 4-min heat treatment (70, 87, and 110 kDa) were purified with the cytoplasmic fraction, whereas only the 70-kDa protein was also found in other cell fractions, including that containing the cellular skeleton. Immediately after a second heat treatment at 45 degrees C for 45 min, the 110-kDa protein from thermotolerant cells also purified extensively with the cellular skeletal fraction. In this regard, the 110 kDa protein behaved similarly to many other cellular proteins, since we observed an overall temperature-dependent increase in the total labeled protein content of the high-salt-resistant cellular skeletal fraction after heat shock. Pulse-chase studies demonstrated that this increased protein content gradually returned to normal levels after a 3-hr incubation at 37 degrees C. The alteration or recovery kinetics of the total labeled protein content of the cellular skeletal fraction after heat shock did not correlate with the dramatic increase in survival observed in thermotolerant cells. The relationship between heat shock proteins and thermotolerance, therefore, does not correlate directly with changes in the heat-induced cellular alterations leading to differences in protein fractionation. PMID- 4039071 TI - The radiation chemistry of some platinum-containing radiosensitizers and related compounds. AB - Oxidation and reduction of cis- and trans-dichlorodiammine platinum II (cis- and trans-PDD), cis-dichlorobis(1-(2-hydroxyethyl)-2-methyl-5-nitroimidazole-N3)-p latinum II (cis-Flap), and cis-dichlorobis(isopropylamine)-trans dihydroxyplatinum IV (Chip) have been studied using pulse radiolysis. Spectra corresponding to platinum in various oxidation states have been observed and several rate constants have been obtained. Reduction of all the compounds, except cis-Flap, produces species of a lower oxidation state of platinum which subsequently have both chloride ligands replaced. Ultimately, these products disproportionate. In the case of cis-Flap, reduction occurred on the nitroimidazole ligand. This was verified by the absence of platinum metal after disproportionation. Oxidation of all four compounds consists of production of a higher oxidation state of platinum followed by replacement of chloride ligands and finally disproportionation of the products. Only cis-Flap and Chip could be reduced by oxidized DNA bases. The one-electron reduction potential of cis-Flap was found to be -370 +/- 10 mV. trans-Flap had almost the same value. It was not possible to measure the potentials of the other compounds since their ligands were replaced rapidly but it is estimated that the one-electron reduction potentials decrease in the order cis- or trans-Flap greater than Chip greater than cis-PDD greater than trans-PDD. PMID- 4039072 TI - Susceptibility to audiogenic seizures in rodents following withdrawal of anticonvulsant drugs. PMID- 4039073 TI - [Transient normalization of the thrombocyte count in chronic idiopathic thrombocytopenia during pneumonia]. AB - A patient is described with severe chronic idiopathic thrombocytopenic purpura. The platelet count was constantly below 20 X 10(9) Tc/L. Therapy with steroids, immunoglobulin-infusion with and without steroids, vincristine and danazol produced no improvement of the thrombocytopenia. During acute pneumonia a transient remission of the platelet count was observed. Antibodies against thrombocytes and immune complexes were not detected. The level of platelet associated IgG was increased before and after infection but was only slightly elevated when platelet count was normal. An attempt to imitate the infection by vaccinating the patient with pneumovac with a view to later splenectomy did not change the platelet count. This observation confirms the hypothesis that elevation of platelet count during infection is due to decreased production of platelet autoantibody. Even severe forms of ITP are potentially reversible. PMID- 4039074 TI - Successful medical treatment of pulmonary petriellidiosis. AB - We have reported a case with culture and serologic evidence of pulmonary infection with Petriellidium boydii treated with intravenous miconazole, resulting in dramatic symptomatic improvement, stabilization of x-ray changes, and clearing of Petriellidium on sputum culture. Although no biopsy was done to establish absolute diagnosis of invasive disease, and thus the results of this case cannot be taken as an absolute criterion for therapy, this may represent the first medical cure of pulmonary infection with this agent. PMID- 4039075 TI - [Morphological study of mucous membranes in the diagnosis and prognosis of inflammatory diseases]. PMID- 4039076 TI - Moderate prenatal carbon monoxide exposure produces persistent, and apparently permanent, memory deficits in rats. AB - The effects of moderate (150 +/- 2 ppm) prenatal carbon monoxide (CO) exposure (maternal HbCO concentrations of 15.6 +/- 1.1%) on learning and memory were assessed in young and aged adult rats using a two-way active avoidance paradigm. In experiment 1, the prenatal CO-exposed rats at 120 days of age acquired a conditioned avoidance response equally well as control animals in a 100-trial session. However, following a 24-hr interval the CO-exposed rats failed to demonstrate significant retention of the task as indicated by the absence of significant improvement in performance over the indicated by the absence of significant improvement in performance over the previous day; control subjects did show significant retention. In experiment 2, in which 120-day-old animals received 50 training trials per day until a criterion of ten consecutive avoidance responses was met, the prenatal CO-exposed subjects again acquired the task as well as control animals. When tested for retention 28 days later, a significant memory impairment was again observed in terms of trials required to reattain the avoidance criterion as well as in total percent avoidance responding. In neither experiment did an analysis of initial or average latency to escape the footshock stimulus reveal any significant alterations. These latter results suggest that the observed performance impairment reflected a memory deficit and not a disruption of sensory, motor, or motivational factors. In experiment 3, prenatal CO-exposed rats approximately 1 year of age (300-360 days of age) showed impairment relative to air-exposed controls in both the original learning and retention of the two-way avoidance response. Again, however, there was no evidence for alterations in performance factors per se. Collectively these data indicate that while young adult rats prenatally exposed to 150 ppm CO demonstrate an associative deficit restricted to memory impairment, aged adults similarly exposed during the prenatal period display a more pronounced deficit similar to that recently reported for animals tested as juveniles. The importance of parametric manipulations in uncovering long-term toxicity is also discussed. PMID- 4039078 TI - A sensitive and specific assay for plasminogen activators. AB - A simple, sensitive and specific assay for plasminogen activators is described. The assay utilizes fluorescein-labeled fibrinogen or fibrin at low concentrations, and enables simultaneous evaluation of the plasminogen and fibrin dependence of the reaction, that is, discrimination of tissue-type and urokinase type plasminogen activators, and non-specific proteolysis. Addition of antisera verify identification of the activator species. The assay reagent contains plasminogen and fluorescein-labeled fibrinogen, to which is added the specimen and then then thrombin, either at the initiation or the termination of the reaction. Supernatant fluorescence is proportional to plasminogen activator concentration. With a four-hour incubation, 1 milliunit (14 pg) of tissue (melanoma) plasminogen activator (TPA) or 2 milliunit (36 pg) of urokinase (UK) may be detected. PMID- 4039077 TI - Studies on the influence of reactants and buffer environment on clot lysis induced by human plasminogen activators. AB - Clot lysis induced by tissue plasminogen activator and urokinase has been studied and the influences of pH, ionic environment and reactant concentrations have been determined. Both pH and ionic strength strongly affect the rate of clot lysis and distinctly different dependency profiles are obtained for tissue plasminogen activator and urokinase. Variations in concentration of plasminogen also profoundly affect the rate of clot lysis, maxima being obtained at different plasminogen concentrations depending on the concentration of fibrinogen. For urokinase, these maxima occurred at about a tenfold higher concentration of plasminogen than for the tissue plasminogen activator. The lysis times are directly dependent on the concentration of fibrinogen. Variation in thrombin concentration did not significantly affect the lysis times. Suitable conditions for the assays of tissue plasminogen activator and urokinase are suggested. PMID- 4039079 TI - [Extrauterine pregnancy in the contralateral tube]. PMID- 4039081 TI - [Pathophysiology and methods of treatment in renal hypertension in renal artery aneurysms]. AB - Aneurysms of the renal artery occur infrequently and remain mostly asymptomatic. A review of the pertinant literature reveals approximately 300 reports. Hypertension is the predominant sign and affects two thirds of all patients, particularly in aneurysms complicated by stenosis or thromboembolism of renal artery, which is caused by the renin-angiotensin-mechanism. A solitary renal aneurysm causes no renal hypertension; 66% of all diagnosed renal artery aneurysms require no treatment. Resection of the aneurysm and direct suture was done in half of all operated patients. Only in 27 cases operative treatment consisted of extirpation and patch-plastic (autologic or alloplastic). Two additional cases in our own hospital with resection and patch-plastic are described. By using those techniques it is possible to normalize renal artery blood flow as well as blood pressure. Other well-known surgical procedures are nephrectomy, aorto-renalbypass and several others. PMID- 4039080 TI - Protective effect of metallothionein inducing metals on lethal toxicity of cis diamminedichloroplatinum in mice. AB - A protective effect of preadministration of the metals Cu, Bi, Zn, Hg, Cd, Ni or Co, against lethal toxicity of cis-diamminedichloroplatinum (Cisplatin; CDDP) was observed in mice. However, the protective effect seems not always to correlate with metallothionein (MT) levels in the liver and kidney of mice treated with one of these metals, suggesting possible participation in this protection of mechanisms other than MT induction by the preadministered metals. PMID- 4039082 TI - [Urinary retention without subvesical obstruction. Differential diagnostic considerations]. AB - Acute urinary retention without subvesical obstruction is associated with neurogenic or nonneurogenic disorders of bladder function. Urodynamic investigations differentiates sensoric and/or motoric disturbances of the micturation. Neurologic and laboratory examinations are necessary to clear the etiology. Symptomatic urological treatment and specific etiological therapy should be used to manage this entity. PMID- 4039083 TI - [Prevention of recurrence in urinary bladder tumors by intravesical instillation treatment with adriamycin]. AB - 109 patients with urinary bladder cancer received post TUR treatment with weekly intravesical instillations of Adriamycin for a period of 6 weeks. 32 patients received a dosage of 10 mg/50 ml physiological NaCl, 35 patients a dosage of 30 mg/50 ml physiological NaCl. We determined the oncolytical value and the value of prophylactically reduced recurrence through urine cytology and endoscopic controls with biopsies. After an observation period of 1 year the result was the same in all groups; 13% had a persistent tumour, 71% remained recurrence free. By raising the dosage of Adriamycin we achieved a reduction in the persister rate from 31% with 10 mg/50 ml NaCl to 6% with 30 mg/50 ml NaCl and to 5% with 50 mg/50 ml NaCl. There was no significant correlation between dosage and recurrence rate. The recurrence rate after a dosage of 10 mg/50 ml was 31%, after 30 mg/50 ml 73% and after 50 mg/50 ml 33%. The increasing recurrence rate correlates with the intensity of local tumour infiltration and with the grading of the primary tumours. PMID- 4039084 TI - [Aminoglutethimide in the treatment of advanced prostatic cancer]. AB - A total of ten previously castrated men with stage D carcinoma received 1000 mg aminoglutethimide and 50 mg/die cortisoneacetate. The patients were evaluated using the criteria of the National Prostate Cancer Project. No patients showed objective response, three patients had reduction of bone pain and subjective improvement. Pretreatment testosterone, prolactine and estradiol levels were measured. Three patients had a statistically significant elevation of testosterone levels. PMID- 4039085 TI - [Colon ureter following bilateral ureteral obstruction caused by aortobifemoral bypass operation]. AB - A case of bilateral ureter obstruction after an aorto-bifemoral bypass operation is described. A new way of treatment in order to restore the draining of urine by uretero-colo-cystoplasty is shown. Regular and punctual urological control after aorto-femoral bypass operation is emphasized. PMID- 4039086 TI - [NMR tomography in urology. Principles--technics--risks--areas of use]. AB - NMR tomography is a new imaging method based on nuclear magnetic resonance. It is possible to obtain sectional views of the human body in all three planes without ionizing radiation. NMR can differentiate soft tissue better than CT, and large blood vessels can be simultaneously evaluated without using contrast medium. The pathological process could be imaged exactly in every examination. Due to the lack of image clarity caused by breathing movement, NMR is not superior to CT when using contrast medium in the epigastrium. Calculation of relaxation times T1 and 2 shows clear differences between tumor and normal tissue. However, contrary to initial expectations. NMR did not permit a type-specific diagnosis to be made. Three-dimensional images improve the process of staging tumors, especially in the retroperitoneal space and in the pelvis. As with CT, metastatic lymph nodes can only be demonstrated when they have reached a size of at least 1 cm. Further studies will be necessary to evaluate the validity of this new imaging method. PMID- 4039087 TI - "Shaker" calf syndrome: a newly recognized inherited neurodegenerative disorder of horned Hereford calves. AB - The clinical and pathological features of a newly recognized, inherited neurodegenerative disorder in horned Hereford calves are described. The disorder is expressed in newborns by tremulous shaking of the head, body and tail, difficulty in rising, a wobbly spastic gait, and aphonia. Transient improvement is followed by deterioration and progressive spastic paraplegia. Generalized tremors can be induced easily by a variety of stimuli, and spinal reflexes may be exaggerated or depressed. The major pathological finding is an excessive accumulation of neurofilaments within neurons of the central, peripheral, and autonomic nervous systems. The involvement of multiple systems of neurons and the similarity with some forms of human motor neuron disease and spinocerebellar degeneration suggest that this unique bovine disease may serve as a suitable animal model for these human neurodegenerative disorders. PMID- 4039088 TI - The experimental production of mastitis in ewes as a determinant of the virulence of ovine ureaplasma strains. AB - Seven out of eight ovine ureaplasma strains inoculated into the mammary gland of suckling ewes produced a mastitis. The pattern of infection was single phase in 5 ewes, persisting for 12-41 days, and biphasic in 3 ewes, persisting in 2 of them until weaning at 60 days and 3 months post-infection. Sucking lambs did not become infected in the eye or nasal areas, and did not transfer infection to the control contralateral glands. PMID- 4039089 TI - [Clinical effects of high-dose immunoglobulin therapy in adults with idiopathic thrombocytopenic purpura]. AB - 15 patients suffering from idiopathic thrombocytopenic purpura were treated in our department with high-dosage immunoglobulins. The daily dosage amounted to between 0.13 and 0.4 g/kg body weight, administered for 4 to 15 days consecutively. The platelet count in 10 patients increased within the first week of treatment, but this increase was maintained for more than 4 weeks in only 3 patients. The average age of these 10 patients amounted to 41.2 years and was significantly lower than that of the remaining 5 patients (66.6 years), who failed to respond. Only one of 4 splenectomized patients responded with an increase in platelet count. Two different immunoglobulin preparations were used. No difference in efficacy was found and both preparations were well tolerated. PMID- 4039090 TI - [Plasma exchange therapy in hematology]. AB - Plasma exchange (PE) is the treatment of choice in emergencies arising in patients suffering from the hyperviscosity syndrome, factor VIII antibody haemophilia, autoimmune haemolytic anaemia or post-transfusion purpura. Apart from these clear indications, the efficacy of PE in other hematological disorders such as thrombotic thrombocytopenic purpura, immune thrombocytopenia, cryoglobulinaemia, rhesus incompatibility, autoimmune cytopenia and AB0 incompatibility with bone-marrow transplantation is less well defined. In such disorders PE can be performed when conventional treatment has failed. PMID- 4039091 TI - [Integrative properties of dominant motivation at the stage of afferent synthesis]. PMID- 4039092 TI - [Delayed reaction and delayed alternation in the cat: common factors and differences]. AB - Cats learned a delayed reaction (DR) sooner than a delayed alternation (DA) in spite of the maximal drawing together of the testing parameters. Short-term memory was suggested to be involved in DR performance whereas DA was based on elaboration of a program of stereotype alternation. DA learning was more effective in an animal receiving additional information on the absence of food in the given food-well after a correct reaction. This fact indicated the use by the animal of the short-term memory about the absence of food in the visited food well in DA test. The effect was not observed at the final stage of DA learning the alternation program having been assimilated. This accounts for strongly expressed deficiency of DA learning abilities in "prefrontal" cats. PMID- 4039093 TI - [PH3 residues in hazelnuts, soybeans and wheat following phosphine fumigation with non-constant concentrations]. AB - In model tests hazelnuts, soy beans and wheat were fumigated with phosphine (PH3) at non constant concentrations. The influence of different concentration characteristics on the fumigation and the decomposition of phosphine residues was investigated in accordance with the fumigation technique. At the beginning the concentration increases, and after attaining the maximum gradually decreases to zero. The level of residues during the fumigation as well as the behaviour of residues during the storage of the fumigated products was monitored with a gas chromatographic method. The residues correlate with the concentration of phosphine, they also pass through a peak. The rate of decomposition of residues which had been formed in the phase of increasing concentration is greater than the rate of residues of equal magnitude which had been formed during the decreasing phase. When the concentration is even the maximum residue occurs later than the maximum concentration; when there is a steep trend both maximums coincide. This behaviour can be explained by the sorption and diffusion of phosphine. A comparison is made with the phosphine concentration which occurs during fumigation in practice. The parameters which produce a constant concentration trend with only one maximum and a non constant trend with an often increasing and decreasing concentration are discussed. The different behaviour of residues in these cases is described. Conclusions are drawn for the practice of fumigation. PMID- 4039094 TI - Combined treatment with cisplatin and radiation therapy for mouse Cl 300 neuroblastoma. AB - The efficacy of the combined treatment of cisplatin and radiation therapy for mouse C1 300 neuroblastoma was studied. Intraperitoneal cisplatin injections and/or radiation were given from 7 to 21 days after inoculation of the tumor cells into the thigh region of A/Jax mice. The combination of 15 Gy radiation and 6 mg/kg cisplatin had an additive effect on both tumour growth delay and survival rate, while that of 30 Gy radiation and 6 mg/kg cisplatin had a synergistic effect. The efficacy of the combined therapy was dependent on the dose of radiation but not on the dose of cisplatin. The normal skin of the mouse was damaged in the similar pattern with both treatments. Thus, cisplatin has a potent radiosensitising effect in the treatment of mouse neuroblastoma. PMID- 4039095 TI - [Initial results with PAC polychemotherapy in the treatment of advanced recurrent breast cancers]. AB - 11 patients with advanced, recurrent mamma cancer were treated by a PAC polychemotherapy. The therapy was well tolerated, the incidence of side effects was low. All patients responded to therapy (7 NED, 3 CR, 1 PR). 2 patients died, one commited suicide, the other died after having developed hepatitis. Of the remaining 9 patients 7 survive recurrence free; medium follow up 20 months. These data are in accordance with results obtained by Kolaric et al. [2] and Forastiere et al. [1] who showed platinum to be effective in the treatment of mamma cancer. PMID- 4039096 TI - [Dynamics of the measurement of urethral pressure in the evaluation of the urethral stress profile]. AB - To obtain exact recordings of the urethral stress profile a pressure rise rate greater than 150 kPa/s is necessary. In this point of view Micro-transducers are advantageous. The different perfusion methods can be improved by the aid of pneumatic-hydraulic infusion systems and low-compliance catheters. Membrane Catheters are involved with some difficulties. PMID- 4039097 TI - [Selective galactophorectomy: technic and indications]. AB - The authors describe the way of operating the selective galactophorectomy and discuss the indications. Each pathological nipple discharge may reveal a carcinoma. The clinical characteristics of the discharge, the results of the cytology, of the mammography and the galactography help to come to a diagnosis. This can only be confirmed after a thorough histological examination of the involved duct. Selective galactophorectomy is a simple operation that hardly leaves any scars. According to the authors, this method has a real advantage to find the diagnosis and to treat pathological nipple discharge. PMID- 4039098 TI - Components of the rat conceptus that account for prolactin inhibition. AB - The secretions from developed concepti in the rat appear to inhibit both the rhythmic nocturnal secretion of prolactin (Prl) during the second half of pregnancy and the neurally mediated Prl release in response to suckling stimulation. In order to identify the parts of the concepti capable of inhibiting Prl secretion, the components of the concepti were systematically removed and their effect on plasma Prl levels was examined. In the first experiment, female rats which were simultaneously pregnant and lactating were tested for Prl secretion in response to suckling stimulation after one of the following treatments: 1) removal of the foetuses only, 2) removal of the foetuses and trophoblasts, 3) removal of the complete concepti. In the second experiment, pregnant rats were tested for the presence of nocturnal Prl surges after either removal of the foetuses and trophoblasts or removal of the entire concepti. The results indicate that after removal of the foetuses alone, the inhibition of Prl secretion remains. Following removal of both the foetus and the trophoblast, leaving the decidua in situ with a supplementary progesterone implant, the decidua still retain a partial capacity to inhibit Prl secretion in response to suckling stimulation, while their inhibitory effect on the nocturnal Prl surges was very minute. Degeneration of the decidua occurred following the removal of the trophoblast, when no exogenous progesterone was supplied. The deterioration of the decidua or total removal of the concepti eliminates the entire inhibition of Prl secretion, both on the nocturnal surges as well as in response to suckling stimulation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4039099 TI - Sling operation for urinary incontinence. AB - 105 women with urinary stress incontinence were treated over an 8-year period. The operations carried out were: 44 Zoedler slings using mersilene and 61 slings using lyodura. Follow-up lasting from 3 to 11 years showed complete failure in 17 patients (16%). The plastic slings of the Zoedler type led to an increased risk of complications such as retropubic infections, rejection of the mersilene, and chronic urinary retention. The lyodura sling was considered good prosthetic material. Our experience shows that a sling operation, as a primary method, may be selected for patients with stress urinary incontinence and a large degree of descent of the anterior vaginal wall and/or uterus. PMID- 4039100 TI - Effect of oestrogen and progesterone on the blood flow in the lower urinary tract of the rabbit. AB - The effects of oestrogen and of oestrogen combined with progesterone were examined on the fractional distribution of cardiac output (blood flow) in the genitourinary tissues of the female rabbit. Oestradiol treatment significantly increased blood perfusion in the uterus, vagina and urethra but caused no change in the perfusion of the urinary bladder or the kidneys. The wet weight of the uterus and vagina increased significantly and in the urethra there was a tendency to weight gain following oestradiol treatment. Progesterone treatment following oestrogen appeared to reduce the effect of oestrogen on both perfusion and weight gain. PMID- 4039101 TI - Plasma branched chain amino acid abnormalities in sake-treated rats. AB - Plasma amino acid abnormalities in rats treated with large doses of sake and whisky for 3 days were investigated under adequate nutritional conditions. A significant decrease in plasma branched-chain amino acid (BCAA) levels was observed in sake- but not whisky-treated rats. However, known factors affecting BCAA levels, such as serum insulin and plasma glucagon levels ahd BCAA metabolizing enzyme (BCAA transaminase and branched chain alpha-ketoacid dehydrogenase) activities in the liver and skeletal muscle, were not significantly altered in the sake group. Furthermore, ethanol-metabolizing enzyme (alcohol and aldehyde dehydrogenases and the microsomal ethanol-oxidizing system) activities in the liver were not altered in the sake group. Other mechanisms need to be considered for explaining the diminished levels of plasma BCAA in sake treated rats. PMID- 4039102 TI - Endoscopic evacuation of intracerebral haemorrhage. High-tec-surgical treatment- a new approach to the problem? AB - A new combination of technologies has been used for the evacuation of intracerebral haemorrhages: The aim is 1. minimal trauma to cerebral tissue in the surgical approach, 2. atraumatic rather than complete removal of blood clots, 3. better prevention of rebleeding. Via a 1 cm burrhole, a 6 mm luminal diameter endoscope is introduced and connected to a video display. Using a suction irrigation system in the endoscope, fluid turbulence and rhythmic pressure variation in the haematoma cavity at 10-15 mm Hg allow the evacuation of the haematoma under visual control. Bleeding vessels can be coagulated using a 1.5 mm luminal diameter Neodym YAG Laser Microtube. If a small craniotomy is performed instead of only a burrhole, facilities for intraoperative ultrasonic display of the haematoma provide additional control thereby enhancing precision and protection of cerebral tissue on approaching the haematoma and during its evacuation. PMID- 4039103 TI - Partial atrioventricular canal associated with discrete subaortic stenosis. PMID- 4039105 TI - N-acetylneuraminic acid concentrations in human milk oligosaccharides and glycoproteins during lactation. AB - Human milk contains a variety of N-acetylneuraminic acid (NANA)-containing oligosaccharides, but the expected range of intake of sialic acid in this form by infants fed human milk is unknown. Two quite different amounts have been reported: 120 mg/liter in pooled, mature human milk (1) and 1400 mg/liter in the milk of a single woman on the 1st day of lactation (2). The normal range of NANA intake in human milk glycoproteins likewise does not appear to have been analyzed previously. Data presented here indicate that both human milk oligosaccharide and glycoprotein NANA decline exponentially over the first 2 months of lactation, decreasing little thereafter. During the first 2 months of lactation, milk from women delivering at term cannot be distinguished from that of women delivering significantly before term (less than 32 wks gestation) with regard to oligosaccharide and glycoprotein NANA. The parallel decrease of sialic acid in these fractions suggests a relationship between sialydation of human milk oligosaccharides and glycoproteins. Human milk NANA concentrations are discussed with regard to reports that exogenous administration of NANA can increase cerebral and cerebellar concentrations of NANA in glycoproteins and gangliosides, and produce long term changes in behavior in rats. PMID- 4039104 TI - Magnetic resonance imaging in hypertrophic cardiomyopathy. AB - Gated magnetic resonance imaging (MRI) was performed using a 0.35-Tesla cryogenic system in 14 patients with hypertrophic cardiomyopathy (HC) in order to define the site and extent of abnormal wall thickness. These studies were compared with 2-dimensional (2-D) echocardiograms. Gated magnetic resonance imaging studies in 12 normal volunteers were used for comparison. In normal subjects and in patients with HC, the sharp demarcation of the myocardial wall permitted measurement of wall thickness. The thickness of the septal and posterolateral walls in normal subjects was 10.2 +/- 0.4 mm (+/- standard deviation) and 10.8 +/- 0.5 mm, respectively, whereas septal thickness in all but 1 patient with HC was 15.0 mm or greater. In patients with HC, septal and posterolateral wall thickness were 2.2 +/- 0.8 cm and 1.3 +/- 0.17 cm, respectively, by MRI. The 2-D echocardiographic measurements for septal and posterolateral walls were 2.4 +/- 0.6 cm and 1.4 +/- 0.7 cm, respectively. The severity and distribution of abnormal wall thickness were comparable on 2-D echo and MRI. Gated MRI is an effective and completely noninvasive technique for demonstrating the presence, site and extent of abnormal wall thickness in HC. The large field of view, ability to image directly in multiple planes, and discrete blood-endocardial interfaces are advantages for cardiovascular imaging. PMID- 4039106 TI - Fluidity of cadaveric blood after sudden death: Part II. Mechanism of release of plasminogen activator from blood vessels. AB - Experiments by the vascular perfusion technique in isolated hind leg of the dog showed that after addition of various vasoactive drugs to the perfusate, fibrinolytic activity (plasminogen activator level) of the effluent was elevated. The effects of the drugs were completely inhibited only by the specific blocker of their receptor on the vascular wall. High K+ level of the perfusate also induced abundant release of plasminogen activator from the vascular wall. PMID- 4039108 TI - Wangiella dermatitidis endocarditis in an intravenous drug user. AB - Wangiella dermatitidis is an infrequently encountered dematiacious fungus that usually causes localized infections of the skin and subcutaneous tissues. This report presents the first well-documented case of natural valve infection caused by this organism as it occurred in intravenous drug abuser. His course has been complicated by relapsing infection of two aortic prostheses and dissemination to the vertebral spine. Treatment with a combination of amphotericin B, rifampin, and ketoconazole has arrested the progression of his infection. The microbiologic features and existing clinical information regarding this fungus are reviewed and in vitro susceptibility data for the present isolate are presented. PMID- 4039109 TI - Treatment of placental vasculature with a neodymium-yttrium-aluminum-garnet laser via fetoscopy. AB - We tested the feasibility of treating placental vascular anomalies with a fetoscopically delivered neodymium-yttrium-aluminum-garnet laser in pregnant ewes. This laser provided sufficient power in an amniotic fluid medium to occlude placental vessels as large as 7 mm in diameter within 6 seconds at a power density of 2000 W/cm2. PMID- 4039107 TI - Minor Xp21 chromosome deletion in a male associated with expression of Duchenne muscular dystrophy, chronic granulomatous disease, retinitis pigmentosa, and McLeod syndrome. AB - We are reporting a male patient who suffered from chronic granulomatous disease associated with cytochrome b-245 deficiency and McLeod red cell phenotype, Duchenne muscular dystrophy, and retinitis pigmentosa. On cytogenetic analysis, he seemed to have a very subtle interstitial deletion of part of band Xp21. Since it was impossible to know whether this material was truly deleted or inserted elsewhere in the genome, somatic cell and molecular studies were carried out. In somatic cell hybrids, the deleted X chromosome was isolated on a Chinese hamster background. Southern blot analysis with 20 single-copy probes, that had been mapped to the X short arm, led to the discovery of one (probe 754) that is missing from this patient's X chromosome and also from his total DNA. This proves that he, indeed, has a deletion rather than a balanced insertion. The results provide cytological mapping information for the X-linked phenotypes present in this patient. Furthermore, probe 754 recognizes a restriction fragment length polymorphism of high frequency that makes it the most powerful probe currently available for linkage studies with X-linked muscular dystrophy. PMID- 4039110 TI - Use and abuse of ventilation tubes. PMID- 4039111 TI - Subarachnoid space: middle ear pathways and recurrent meningitis. AB - Congenital bony abnormalities of the inner ear may result in a communication between the middle ear and the subarachnoid space. Patients with this anomaly often present with recurrent meningitis associated with acute otitis media or with middle ear fluid. This article presents three cases of recurrent meningitis with open middle ear--subarachnoid space connections. The first two cases involve a cerebrospinal fluid leak into the middle ear via the oval window, both patients having a Mondini-type of inner ear deformity. The pathway in the third case opened into the middle ear along the horizontal portion of the facial nerve. Computed tomography (CT) scanning with metrizamide and differential density calculations helped to identify the abnormal pathway and to confirm that the leak has been closed postoperatively. Use of the CT scanner in these cases can be helpful in planning the surgical closure and in postoperative follow-up. PMID- 4039112 TI - Presence of Gc (vitamin D-binding protein) and interactions with actin in human placental tissue. AB - The distribution of Gc protein and actin and their interactions were studied in normal full-term human placentae. Both Gc and actin were detected by physicochemical analysis of isolated trophoblast membranes. Immunofluorescence of native placental sections showed fluorescence for both proteins on smooth muscle cells lining the fetal stem vessels, intervillous fibrin, villous fibrinoid, trophoblast membrane, and cytoplasm of villous stromal cells. Binding of Gc was demonstrated by prior incubation of sections with purified Gc which led to a striking increase in intensity of Gc fluorescence, but actin fluorescence was unaffected by this procedure and by preincubation with actin. Endogenous Gc and actin could also be removed by washing of tissue sections with chaotrope--3 M KCl or 3 M NH4SCN, denaturant--6 M urea, or glycine-HCl pH 3.8, as judged by fluorescence and SDS-PAGE of the wash supernatant. Phenotypic analysis of Gc eluted from trophoblast membranes and of corresponding matched maternal and fetal cord sera by isoelectric focusing indicated that trophoblast Gc was of predominantly maternal origin. Although the roles of Gc and actin in the placenta are unknown, these results indicate that Gc may be another maternal protein for which specific binding sites are expressed on the membrane of placental trophoblast. PMID- 4039113 TI - Oleander tea: herbal draught of death. AB - A woman died after drinking herbal tea prepared from oleander (Nerium oleander) leaves. This case demonstrates the cross-reactivity between the cardiac glycosides in oleander and the digoxin radioimmunoassay. Digoxin-specific Fab antibody fragments have not been used in oleander poisoning, but these might prove to be lifesaving. Treatment of oleander toxicity is aimed at controlling arrhythmias and hyperkalemia; inactivation of the Na-K ATPase pump, however, can make treatment difficult. PMID- 4039114 TI - High-dose cisplatin therapy for cancer of the ovary: neurotoxicity. PMID- 4039115 TI - [Hypertrophic myocardiopathy with isolated obstruction of the right ventricle]. AB - The authors report one case of biventricular hypertrophic cardiomyopathy in a 23 year old female patient with severe localized obstruction of the right ventricle (105 mm Hg gradient, almost complete angiographic disappearance of the middle and apical portions of the right ventricle during systole). Echocardiography, hemodynamic findings, and angiography demonstrated nonobstructive involvement of the left ventricle. Among other family members, only her father was noted to have minimal hypertrophic cardiomyopathy. A favorable response to therapy was obtained over 14 months with 320 mg of propranolol given daily (disappearance of palpitations and ventricular tachycardia which had previously been noted on a continuous 24 hour recording before treatment). Other very rare similar cases in the literature are analyzed. It is not possible to distinguish these cases from those with predominantly left ventricular involvement by clinical and radiological findings alone. However, the ECG can often demonstrate right ventricular involvement (right ventricular hypertrophy and/or right bundle branch block). Lastly, it appears that biventricular hypertrophic cardiomyopathies in young patients can initially be localized to only the right ventricle. PMID- 4039116 TI - Symptoms related to menstruation in adolescent Swiss girls: a longitudinal study. AB - Symptoms related to menstruation are reported in 140 Swiss girls according to postmenarcheal and chronological age. Premenstrual abdominal pains were present in 9-28% of the girls, depending on postmenarcheal age (i.e. years after menarche) (2-30% depending on chronological age). Dysmenorrhoea occurred in 44 64% of the girls according to postmenarcheal age (51-67% according to chronological age). Occasional severe dysmenorrhoea was the type most often reported, by 20-35% of the girls. Large intra-individual and inter-individual variabilities in the occurrence and severity of dysmenorrhoea were observed. The frequency of dysmenorrhoea increased in the first three postmenarcheal years and decreased thereafter. The prevalence of premenstrual headache was low, 0-5%. The frequency of headache during menstruation was 2-11% according to postmenarcheal age (2-19% by chronological age) which was low in comparison with other studies. Severe menstrual headache was more often reported than mild headache. Frequency of severe headache decreased in higher age groups. Other reported symptoms related to menstruation were general discomfort in 1-10% of the girls and premenstrual vaginal discharge in 10-22% according to postmenarcheal age (3-17% according to chronological age). Severe vaginal discharge was more frequent than mild discharge, 8-20% versus 0-3%. The frequency of vaginal discharge increased from the first to the fourth year after menarche. PMID- 4039117 TI - Pharmacokinetics of aztreonam in patients with gram-negative infections. AB - Aztreonam pharmacokinetics were assessed in seven patients treated for urinary (n = 6) or lower respiratory (n = 1) tract infections. Each patient was studied twice, at the beginning and end of therapy (7 to 10 days). The patients enrolled had normal to moderately impaired renal function; a good correlation (r2 = 0.90) between serum aztreonam clearance (CL) and creatinine clearance (CLCR) was observed (mean CL/CLCR ratio = 1.11). CL ranged from 21.6 to 121 ml/min per 70 kg, and the half-life ranged from 1.6 to 8.9 h. The mean steady-state volume of distribution (0.16 +/- 0.05 [standard deviation] liter/kg) approximated the extracellular fluid volume. Protein binding of aztreonam in serum (mean, 30%) was lower than that reported in healthy adults. CL increased significantly from the first to the last day of the study, probably reflecting increasing renal function. After multiple dosing (1 g every 8 h), no significant accumulation of aztreonam was observed. Overall, the disposition of aztreonam is comparable in infected and noninfected subjects, and dosing adjustments in patients with renal impairment should be facilitated by the good correlation between CL and CLCR. PMID- 4039118 TI - Efficacy and safety of aztreonam-clindamycin versus tobramycin-clindamycin in the treatment of lower respiratory tract infections caused by aerobic gram-negative bacilli. AB - A total of 80 patients were randomized to receive either aztreonam or tobramycin for the treatment of lower respiratory tract infections caused by gram-negative bacilli; all these patients received clindamycin concomitantly. A total of 53 patients were randomized to receive aztreonam-clindamycin; of these, 46 were clinically evaluable and 39 were bacteriologically evaluable. Of the 46 clinically evaluable patients, 41 were considered cured, 3 failed to be cured, and 2 died during the study period of unrelated causes. Of the 39 bacteriologically evaluable patients, 36 were considered cured, and 3 failed to be cured. There were 26 clinically evaluable patients in the group randomized to receive tobramycin-clindamycin. Of them, 22 patients were considered cured, 3 failed to be cured, and 1 died of unrelated causes during the study period. There were 18 bacteriologically evaluable patients in the tobramycin-clindamycin group; 17 were cured, and 1 failed to be cured. The most common pathogens isolated from the patients were Klebsiella pneumoniae, Escherichia coli, and Pseudomonas aeruginosa. All of the isolated organisms were susceptible to both tested antibiotics, except for a strain of Pseudomonas cepacia resistant to both tested antimicrobial agents and a strain of Enterobacter aerogenes and one of P. aeruginosa that were resistant to aztreonam. Very few adverse reactions related to the antibiotics were seen. These effects, when present, were transient and comparable in both studied groups, except for renal-function tests, which were altered in 7.7% of the patients randomized to receive tobramycin-clindamycin and in none of the patients randomized to receive aztreonam-clindamycin. Aztreonam clindamycin is safe and effective for the treatment of lower respiratory tract infections caused by aerobic gram-negative bacilli when the organisms are susceptible. PMID- 4039119 TI - Specific inhibition of fungal sterol biosynthesis by SF 86-327, a new allylamine antimycotic agent. AB - SF 86-327 is a new antimycotic agent of the allylamine type. Its primary action appears to be the inhibition of ergosterol biosynthesis at the point of squalene epoxidation, as was previously found with the related compound naftifine. Biosynthesis was measured by incorporation of [14C]acetate into sterols in cells of Candida albicans, Candida parapsilosis, Torulopsis glabrata, and the dermatophyte Trichophyton mentagrophytes. There was a positive correlation between the SF 86-327 concentrations needed for inhibition of growth and of sterol synthesis in these four fungi. The greater antifungal efficacy of SF 86 327 in comparison with naftifine was also reflected in the relative activities of the two compounds as sterol synthesis inhibitors. Inhibition was maximal at neutral pH. A similar degree of inhibition was found in cell-free extracts when [14C]mevalonate was used as substrate. In all cases, inhibition of sterol synthesis was accompanied by a parallel accumulation of labeled squalene. SF 86 327 and naftifine had no significant effect on initial enzymes of the ergosterol pathway, measured by incorporation of [14C]acetyl coenzyme A, or on steps distal to squalene epoxidation, measured by conversion of labeled squalene 2,3-epoxide or lanosterol. Both allylamines were highly selective for fungal, as opposed to mammalian, sterol biosynthesis. SF 86-327 caused slight inhibition of squalene epoxidation in a rat liver cell-free system, but at concentrations three to four orders of magnitude greater than those required for inhibition of the fungal pathway. PMID- 4039120 TI - Penetration of aztreonam into human bronchial secretions. AB - Nine intubated patients were given a single, 2-g intravenous dose of aztreonam over 5 min. Samples of serum and bronchial secretion were obtained 2, 4, and 8 h after administration and assayed for aztreonam content. The mean concentrations in bronchial secretion ranged from 1.9 to 5.2 micrograms/ml and tended to be highest at 4 h. The concentrations in bronchial secretion varied from patient to patient, but each patient had one or more bronchial secretion samples that contained at least 2.7 micrograms of drug per ml. PMID- 4039121 TI - Biliary excretion of platinum in a patient treated with cis dichlorodiammineplatinum (II). AB - Biliary excretion of platinum was measured in a patient receiving an intravenous infusion of cis-dichlorodiammineplatinum (II). Over a 3-day period, less than 1% of the administered platinum was detected in the bile, and 47% appeared in the urine, indicating that biliary excretion is a minor route of elimination. PMID- 4039122 TI - Structure-function relationships of retinoids in their effects on retinol-binding protein metabolism in cultured H4II EC3 liver cells. AB - Studies were conducted to explore the structural features of retinoids that may be required to stimulate the secretion or production of retinol-binding protein (RBP) by H4II EC3 rat hepatoma cells in culture. Sixteen retinoids, that differed from all-trans-retinol in the cyclohexene ring, the polyene side chain, and/or the functional end group, were each incubated with H4II EC3 cells, and RBP secretion and accumulation were determined by radioimmunoassay. A number of retinoids, in addition to retinol, effectively stimulated RBP secretion. The results suggest that an intact cyclohexene ring may be necessary for the stimulation of RBP secretion. In contrast the system did not exhibit much specificity with regard to either the structure of the side chain or the nature of the end group. No relationship was found between the ability of a retinoid to stimulate RBP secretion and production and its biological activity. The biologically active retinoid, 13-cis-retinoic acid, was inactive in the present system, whereas the biologically inactive perhydromonoeneretinol was moderately effective in stimulating both RBP secretion and accumulation. In contrast, there appeared to be some relationship between the ability of different retinoids to stimulate RBP secretion and their ability to bind to RBP. In general, retinoids that had previously been shown to bind to RBP produced a greater stimulation of RBP secretion than those that did not bind to RBP. The secretion of RBP obtained with a given retinoid was not well correlated with the net accumulation of RBP. For example, retinoyl amide did not stimulate RBP secretion but was moderately effective in stimulating RBP accumulation. Thus, the secretion of RBP does not appear to be necessary for the stimulation of the net accumulation of RBP. PMID- 4039123 TI - [Two-route chemotherapy using a combination of anticancer agents and antidotes]. AB - We studied the effect of "two-route chemotherapy (TRC)" in which an anticancer drug and its antidote are respectively administered locally and systemically. This therapy reduced the side effects and consequently enabled an increased dose of anticancer agents to be given. The first trial of TRC using a combination of nitrogen mustard N-oxide and its antidote cysteine was effective for the treatment of metastatic liver tumors in rats. Recently, we obtained a remarkable antitumor effect by giving a combination of cis-diamminedichloroplatinum (II) (CDDP) and sodium thiosulfate (STS) for peritoneal dissemination, bladder tumors, and liver and lung metastasis, in experimental animals, based on the evidence that STS inactivates the toxicity of DDP. This TRC using DDP and STS is now under clinical trial, and remarkable antitumor effects without nephrotoxicity have been observed. We also present evidence that the protective effect of STS against DDP toxicity is mainly due to the inactivation of active platinum in the blood stream and partly due to the diuretic effect of STS. PMID- 4039124 TI - [Systemic chemotherapy with super-high dose cisplatin and sodium thiosulfate (STS) rescue in mice]. AB - We have devised a new systemic chemotherapy using cisplatin (DDP) with sodium thiosulfate (STS) rescue; basically, STS was given repeatedly 6 hours after DDP administration combined with metoclopramide. The effect of STS-rescue on the antitumor activity of DDP was studied using a BALB/c syngeneic fibrosarcoma (KKN 1). A graded dose of DDP was given i.p. with or without STS-rescue and its effects were evaluated according to N. C. I. protocol. A DDP dose-related antitumor activity was observed and the minimal effective doses were calculated as 8.2 and 9.8 mg/kg for groups treated with DDP alone and with STS-rescue, respectively. When STS-rescue was combined, however, super-high doses of DDP (9 16.5mg/kg) could be administered and this resulted in a 52% increase in chemotherapy index. PMID- 4039125 TI - [Effects of calcium influx blocker on the cellular transport of Adriamycin]. AB - Effects of the calcium influx blocker, verapamil, on the cellular transport of adriamycin (ADR) were studied using the technique of flow cytometry. A marked increase in intracellular ADR accumulation was brought about by verapamil treatment. Flow cytometric analysis suggested that this augmentation of cellular ADR content was due to the inhibition of active ADR efflux from the cells. This inhibitory effect of verapamil was dependent on the concentration of the calcium influx blocker in the culture medium. PMID- 4039126 TI - Discrete sub-aortic stenosis and ventricular septal defect. AB - We present details of 15 children, aged 3 months to 11 years, with discrete sub aortic stenosis and ventricular septal defect. We emphasise a high index of clinical suspicion and echocardiography as the best means of diagnosing this dangerous combination. Physical signs were those of ventricular septal defect in all patients, with auscultatory evidence of additional sub-aortic stenosis in only one. Five patients had a short early diastolic murmur of mild aortic incompetence. The electrocardiograph showed isolated left ventricular hypertrophy in eight patients. Cardiac catheterisation and angiography identified the ventricular septal defect in all cases but detected the sub-aortic stenosis in only eight. Cross sectional echocardiography showed both lesions in all 11 patients to whom it was available. PMID- 4039127 TI - Long-term effects of dinoseb and paraquat, both individually and combined, on embryonic development and hatching success of Fasciola hepatica miracidia. PMID- 4039128 TI - Ovicidal effects of albendazole in human ascariasis, ancylostomiasis and trichuriasis. AB - Albendazole, a broad spectrum anthelmintic, was administered as a 400 mg single dose to 20 patients harbouring Ascaris (ten cases), hookworms (four cases each of Ancylostoma duodenale and Necator americanus) and trichuriasis (ten cases). Faeces were obtained before treatment and during the following five days. Coprocultures were made for 90 days for Ascaris and Trichuris eggs, hookworm eggs were cultured by the Harada-Mori technique for at least eight days. Albendazole was ovicidal against all four genera of nematodes. PMID- 4039129 TI - Single ventricle (single- or double-inlet) complicated by subaortic stenosis: surgical options in infancy. AB - Intracardiac obstruction to the systemic circulation can develop in patients with many forms of congenital heart disease. When transposition of the great arteries accompanies tricuspid atresia, narrowing of the ventricular septal defect (VSD) leads to subaortic stenosis. In a similar fashion, a restrictive bulboventricular foramen compromises systemic arterial outflow in patients who have single left ventricle with subaortic outflow chamber. The same effect can be seen in VSD closure in mitral atresia with normally related great vessels. Although some forms of single ventricle can be treated by ventricular septation, the modified Fontan procedure can be more generally applied to this entity. Pulmonary vascular resistance must be low, however, which excludes the application of the Fontan principle in infants. While pulmonary artery banding may protect the lungs from the development of excessive pulmonary vascular resistance, it may also accelerate the development of subaortic obstruction. We have successfully applied the Norwood operation, as described for hypoplastic left heart syndrome, to palliate subaortic stenosis due to restrictive VSD in 3 infants with single ventricle or atrioventricular valve atresia. Consideration should be given to a primary Norwood procedure in infants with single ventricle in whom subaortic stenosis is likely to develop. Patients who do receive pulmonary artery bands should be followed closely for the development of subaortic stenosis and should undergo an early, physiologically corrective operation if it occurs. PMID- 4039131 TI - Acute deafness. A complication of high-dose cisplatin. AB - Acute, profound cisplatin-induced deafness has rarely been reported. Ototoxic reactions to cisplatin in the past have been subclinical, with most hearing loss occurring in the high-frequency range. A patient was treated with ultra-high-dose cisplatin who suffered acute profound deafness. Methods are suggested for preventing similar complications in other patients given cisplatin in high-dose ranges. PMID- 4039130 TI - Arterial infusion of dacarbazine and cisplatin for recurrent regionally confined melanoma. AB - We treated nine patients who had metastatic malignant melanoma confined to one extremity (8/9) or the vulva (1/9) with arterial dacarbazine and cisplatin at respective doses of 800 and 90 mg/sq m. We percutaneously introduced catheters into the extremity or regional artery under fluoroscopy by the Seldinger technique, removed them at the end of the infusions, and repositioned them at four-week intervals for repeated treatment cycles. One patient achieved a complete remission, three patients had partial remissions, and five patients' disease was stable. The group median survival will exceed 19 months. Three patients with stable disease died 6, 18, and 19 months after treatment initiation, respectively. The toxic effects were primarily nausea and vomiting, pain in the infused extremity, and local erythema. Arterial dacarbazine and cisplatin offer a more effective and less toxic alternative to higher-dose single agent arterial cisplatin for locally advanced malignant melanoma. PMID- 4039132 TI - Resolving the effects of phenotype and social background on mate selection. PMID- 4039133 TI - Increase in aggressiveness of male mice carrying a reciprocal translocation, T(10,13), in the heterozygous state. PMID- 4039134 TI - Human tissue-type plasminogen activator. Production in continuous serum-free cell culture and rapid purification. AB - A simplified procedure for the production and purification of human tissue-type plasminogen activator (t-PA) is described. Bowes-melanoma cells were maintained in continuous serum-free culture. The cell nutrient consisted of Dulbecco's modified Eagle's medium (DMEM) supplemented with insulin (5 mg/litre), transferrin (5 mg/litre), progesterone (1 nM), cortisol (10 nM), aprotinin (2 X 10(4) units/litre) and a mixture of trace elements. t-PA accumulated in the culture medium at a rate of 40 units/day per ml and was harvested every third day. Cell losses during each harvest, leading to a steady decline of enzyme yields, were compensated for by treating the cells with 5% (v/v) fetal-bovine serum in DMEM every 6-8 weeks. t-PA was rapidly purified by a combination of cation-exchange chromatography and gel filtration. The procedure yielded mainly single-chain t-PA of a specific activity of 80 000 to 100 000 units/mg. PMID- 4039135 TI - Role of antizyme in degradation of ornithine decarboxylase in HTC cells. AB - A good correlation was observed between the reciprocal of the half-life of ornithine decarboxylase (ODC) activity in the presence of cycloheximide and the relative amount of ODC-antizyme complex to total ODC (free ODC plus complexed ODC) activity in HTC cells examined at various times after cell dilution or change of medium. Pretreatment of cells with putrescine increased the relative amount of ODC-antizyme complex and decreased the half-life of ODC decay. These results suggested that antizyme plays a key role in ODC degradation. PMID- 4039136 TI - Testosterone-estradiol-binding globulin binds to human prostatic cell membranes. AB - Specific binding sites for human testosterone-estradiol-binding globulin have been found on human prostatic cell membranes. Scatchard analysis reveals both a high and a low affinity binding site for [125I]testosterone-estradiol-binding globulin. The high affinity site is specific for testosterone-estradiol-binding globulin, whereas the low affinity site also binds human corticosteroid-binding globulin and human transferrin. PMID- 4039137 TI - The interaction of calmodulin with erythrocyte membrane proteins. AB - The method of sedimentation equilibrium in an air-driven ultracentrifuge (Airfuge) has been employed to investigate the interaction of 125I-calmodulin with the cytoskeletal components of the human red cell membrane. The results indicate significant calcium-dependent calmodulin binding activity in the low and high ionic strength extracts of the human erythrocyte membrane. The interaction of 125I-calmodulin with the low ionic strength extract proteins is analysed quantitatively. Further purification of the high ionic strength extract comprising mainly band 2.1 and band 4.1 results in the elution of calmodulin binding activity in a purified fraction of band 4.1. PMID- 4039138 TI - The amino acid sequence of equine milk lysozyme. AB - The amino acid sequence of equine milk lysozyme has been elucidated. The study involves the determination of the sequence of the N-terminal region of the whole protein, cyanogen bromide fragments, tryptic and chymotryptic peptides and fragments produced by chemical cleavage after tryptophan residues. The protein consists of a single chain of 129 amino acid residues and has a Mr of 14647. While equine milk lysozyme has the essential features of a c(chick)-type lysozyme, there is only 51% sequence homology with human milk lysozyme and 50% with domestic hen egg white lysozyme. Some of the implications of the large number of differences are discussed. PMID- 4039139 TI - Diurnal fluctuation and pharmacological alteration of mouse organ glutathione content. AB - Mouse liver glutathione content showed a diurnal variation with a maximum GSH + 2 GSSG content at 6 to 10 a.m. of 62 +/- 8 nmole per mg protein and a minimum of 42 +/- 7 at 6 p.m. Starvation for more than 24 hr decreased the hepatic glutathione content to 22 +/- 3 nmole/mg protein and abolished the diurnal rhythm. Artificial reversal of the feeding habit of the animals reversed the diurnal rhythm. Kidney, spleen and lung glutathione contents showed no such rhythm. The organ glutathione content decreased by 50% or more upon starvation. The increase of the liver glutathione content by injection of either free or liposomally entrapped GSH to starved animals was not dependent on the time of administration. The physiological maximum level could not be exceeded by this treatment. It was not possible to influence the glutathione content of kidney, lung or intestine by glutathione injections in either form. Intravenous injections of equimolar doses of 2,3-dimercaptopropanol, 2-mercaptoethanesulfonic acid, N-2 mercaptopropionylglycine, D-penicillamine, or cysteamine did not lead to any significant change in liver, kidney, spleen or lung glutathione contents 2 hr after administration. Intravenously given N-acetylcysteine, methionine, GSH or GSSG restored liver glutathione levels of starved animals to the contents observed in the fed state. The diurnal hepatic variation of GSH caused by the food intake habit of the animals may limit the capacity of the intracellular detoxication system. PMID- 4039140 TI - Healing of malignant hypertensive arteriopathy in Dahl rats by nifedipine. AB - Pathomorphological studies were undertaken to investigate the therapeutic effect of the Ca2+-antagonist nifedipine on malignant hypertensive arteriopathy in Dahl salt-sensitive rats. The individual course of disease was followed by comparing pre-treatment biopsies of the mesenteric arteries with post-treatment findings at necropsy. Within seven weeks, continuous therapy with nifedipine resulted in healing of early vascular lesions and in partial repair of the more advanced ones. Under normalization of blood pressure, vascular fibrinoid exacerbations were prevented and existing intramural fibrin insudates were completely or partially removed. Lamellar fibroelastosis of the intima occurred as a characteristic of repair. PMID- 4039141 TI - Tissue distribution of amiodarone and desethylamiodarone in rats after multiple intraperitoneal administration of various amiodarone dosages. AB - Tissue distribution of amiodarone (Cordarone) and desethylamiodarone in the rat was studied after repeated intraperitoneal administration of the drug. Tissue and serum concentrations of amiodarone and desethylamiodarone were determined by high performance liquid chromatography. The levels of amiodarone and desethylamiodarone in serum and tissues obtained after repeated intraperitoneal application of doses varying from 25 mg to 200 mg/kg show that the accumulation of amiodarone and desethylamiodarone in the rat is dose-dependent and both drugs are preferentially distributed in decreasing order in adipose tissue, lung, liver, kidney and thyroid gland. The penetration of the drug and its metabolite into brain was poor and with all the applied dosages brain levels were considerably lower than the corresponding serum levels. Desethylamiodarone serum and tissue concentrations were substantially lower than the corresponding amiodarone concentrations and varied from 1 to 48% (mean 15%) depending on the dosage used and the kind of tissue. The amiodarone tissue/serum concentration ratios were exceptionally high in adipose tissue (1,000-4,000) and moderate to high in the other tissues except brain (5-90), and indicate an extensive distribution of the drug with fat as a reservoir with a large storage capacity. The levels of amiodarone and desethylamiodarone, obtained with 50 mg/kg and 100 mg/kg dosages, showed in function of time clearly an increase in serum and tissues. The observed amiodarone tissue/serum ratios in function of time revealed no further significant increase (p less than or equal to 0.05) after 3 injections over a 6-day period, indicating the attainment of "steady-state".(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4039142 TI - Kinetic study of deuterium-labelled polyenphosphatidylcholine after oral administration to rats. AB - Deuterium-labelled di-[( 15,15,16,16-2H4]-linoleoyl) -3-sn-glycero-phosphocholine was used as a tracer of the major component of soybean polyene-3-sn phosphatidylcholine to study the pharmacokinetics of a natural product after oral administration to rats. For this purpose a method was developed to isolate the phosphatidylcholine fraction from blood in a highly purified form. Only 200 pg deuterium-labelled fatty acid generated from the phosphatidylcholine fraction and a ratio of one molecule of deuterium-labelled stearic acid to 500 molecules of stearic acid are necessary for a reproducible measurement by gas chromatography/mass spectrometry. The highest amount of di-[( 15,15,16,16-2H4] linoleoyl) -3-sn-glycerophosphocholine (0.12% dose/ml, i.e. 2.1% of the maximum absorbed dose) was detected in blood 6 h after administration. The results are comparable with those found after administration of di-[l-14C]-linoleoyl-3-sn glycerophosphocholine. Hence it is possible to use deuterium-labelled polyenphosphatidylcholine instead of radioactively labelled polyenphosphatidylcholine, especially if a harmless tracer is required. PMID- 4039143 TI - Effects of exepanol-HCl, metoclopramide and domperidone on the lower esophageal sphincter of dogs. AB - The actions of rac. 3,5-cis-2,3,4,5-tetrahydro-3-methylamino-1-benzoxepine-5-ol hydrochloride (prop. INN exepanol-HCl, KC 2450), metoclopramide and domperidone on the resting pressure of the lower esophageal sphincter (LES) were studied in anesthetized and conscious beagle dogs using pull-through manometrical methods. Exepanol-HCl proved to enhance the LES pressure (LESP) significantly both in anesthetized and conscious dogs. The action of domperidone which was used as reference compound in the anesthetized dog experiments was less pronounced. In conscious dogs the actions of exepanol-HCl and metoclopramide were comparable. Domperidone was not active in this test. PMID- 4039144 TI - Capillary gas chromatographic determination of biperiden in human plasma. AB - A method with internal analogue standardization is described for the determination of 1-(bicyclo[2.2.1]hept-5-en-2-yl)-1-phenyl-3-piperidinopropan-1 ol hydrochloride (biperiden hydrochloride, Akineton). The method involves a multi step clean-up procedure and subsequent determination by capillary gas chromatography using temperature gradient and nitrogen-sensitive detection. There is no interference by plasma components and biperiden metabolites in plasma extracts. When using a 2-ml sample the lower limit of detection is 0.09 ng/ml, the lower limit of determination about 0.25 ng/ml. Interassay variation coefficients decrease from approximately 14% at the lowest concentration to about 7% at 1.2 ng/ml and above. PMID- 4039145 TI - Continuous body fluid monitoring for zomepirac by fully automated high performance liquid chromatography. AB - A sensitive, specific and rapid determination of 5-(4-chlorobenzoyl)-1,4-dimethyl 1H-pyrrole-2-acetic acid sodium salt dihydrate (zomepirac sodium, Zomax) in human plasma and urine by a continuous body fluid monitoring system based on high performance liquid chromatography is described. Samples are directly injected into the apparatus which consists of commonly available HPLC-modules. Manual sample clean-up procedures as well as the addition of an internal standard are not needed. Using 50-microliter aliquots, the detection limit is lower than 0.05 microgram/ml and the calibration ranges from 0.5 to 100 micrograms/ml are linear for both, spiked samples and references. The recovery is 97% for plasma and 95% for urine samples at a sampling rate of about 15 samples/h. PMID- 4039146 TI - [The bioavailability and pharmacokinetics of two carbocysteine preparations after single and multiple dosing]. AB - The relative bioavailabilities and pharmacokinetic profiles of 2 carbocisteine preparations (capsules, granulate) were evaluated in a single dose and a steady state study. 10 healthy volunteers took in a randomized, 2fold cross over design 750 mg 3-(carboxymethylthio)alanine (carbocisteine, Transbronchin) (1 portion of the granulate or 2 capsules) as a single dose or for 4 days 3 times a day (every 8 h) 1 portion of the granulate or 2 capsules, respectively. During the saturation phase the pre-dose serum levels in the morning were determined and on day 5 - after a last dosing the elimination kinetics were evaluated. The same time frame of blood withdrawals was used for the evaluation of serum kinetics after single dosing. The new developed gaschromatographic method for the rapid, sensitive and reliable quantitative determination of carbocisteine in serum saves not only a lot of time but also improves the detection limit and selectivity by a factor of approx. 10. The studies revealed bioequivalency of the carbocisteine granulate and capsule preparations. After multiple dosing, no cumulation of the carbocisteine serum levels occurred. A comparison of the AUCo-infinity and AUC tau (single/multiple dosing, respectively) showed linear pharmacokinetics without enzyme induction or saturation phenomena in man. PMID- 4039147 TI - The influence of aluminium hydroxide on the bioavailability of feprazone. Single dose study. AB - The influence of aluminium hydroxide (given as a suspension, Aludrox) on the oral bioavailability of feprazone was tested. The degree and speed of absorption of feprazone from capsules (400 mg feprazone as a single dose; 8 volunteers) was investigated by determining plasma levels of feprazone and one of its metabolites using an HPLC method. No statistically significant change in feprazone kinetics caused by the antacid was evident. Cmax (means +/- SEM) decreased from 40.6 +/- 2.9 to 36.25 +/- 1.4 micrograms/ml; the mean area under the plasma level time curve was somewhat higher after additional administration of aluminium hydroxide (n. s.). PMID- 4039148 TI - Quantitative structure-activity relationship studies of non-aromatic analogues of ethanolamine as inhibitors of phenylethanolamine N-methyltransferase. AB - The phenylethanolamine N-methyltransferase inhibition potency of non-aromatic ethanolamines is found by regression analysis to be significantly correlated with van der Waals volume, Vw. For the proper inhibition of this enzyme the size of a substituent on beta-carbon of ethanolamine chain should be comparable to the cavity size of enzyme and there should be no other bigger group present on this carbon, which can cause a steric crowding, when the molecule approaches the reactive site of the enzyme. PMID- 4039149 TI - The effect of coenzyme Q10 on the action of phospholipase. AB - Using dimyristoyl L-alpha-phosphatidylcholine as a substrate, the effect of coenzyme Q10 on phospholipid digestion by phospholipase A2 and phospholipase C was investigated. Free myristic acids released by phospholipase A2, and myristic acids of dimyristoyl glyceride released by phospholipase C were methylated and determined quantitatively by gas-chromatography. Phospholipase A2 or phospholipase C released myristic acids dose-dependently from the substrate. Coenzyme Q10 prevented dose-dependently the hydrolysis of the substrate caused by phospholipase. These results suggest that pharmacological action of coenzyme Q10 could be attributed to its protection of membrane phospholipids against the attack of phospholipases. PMID- 4039150 TI - Protective effect of coenzyme Q10 on erythrolysis induced by octoxinol or hypotonic salines. AB - Using dog erythrocytes, the effect of coenzyme Q10 (CoQ10) on the resistance of the erythrocyte membrane was investigated. Hemolysis was induced either by Octoxinol (Triton X-100) a well-known detergent, or by hypotonic salines. Although no detectable CoQ10 was observed in erythrocyte without CoQ10 addition, the increment in CoQ10 content in erythrocyte was found to be proportional to the doses of CoQ10 added to the erythrocyte samples. Administration of CoQ10 inhibited significantly the hemolysis induced either by octoxinol or hypotonic salines by a dose-dependent manner. These results suggest that CoQ10 incorporated into the erythrocyte increased the resistance of erythrocyte membrane by a direct structural effect on the membrane. PMID- 4039151 TI - [Synthesis of C14-flupirtine maleate]. AB - Starting from 14C-p-fluorobenzoic acid the synthesis of 14C-labelled 2-amino-3 ethoxycarbonylamino-6-(p-fluorobenzylamino)-pyridi ne maleate (flupiritine maleate, D 9998) is described. PMID- 4039152 TI - [General pharmacologic studies on the analgesic flupirtine]. AB - In the present study the general pharmacological properties of ethyl-N-[2-amino-6 (4-fluor-phenylmethylamino)pyridin-3-yl]carbama te (flupirtine, D 9998), a structural new analgesic, are described. In several tests with mice flupirtine shows a centrally depressant component of action. However, regarding undesirable side effects as ataxia, inhibition of motor activity etc. this action is, with respect to the analgesic effective doses less pronounced than those of comparable analgesics, for instance phenacetin. In relatively low doses flupirtine antagonizes tremor induced by oxotremorine in mice. This activity is probably not caused by a central anticholinergic action, because other anticholinergic effects have not been observed. It should be pointed out that flupirtine antagonizes the morphine-induced tail phenomenon in mice in relatively low doses. This action obviously differentiates flupirtine from opiates. Up to high doses flupirtine does not cause catalepsia in mice, consequently its centrally depressant activity does not resemble that of reserpine and also is not comparable with those of neuroleptic agents. The corneal and pinnal reflexes are not influenced by flupirtine and the righting reflex is slightly delayed in high doses. The anticonvulsive activity of flupirtine observed in the pentetrazol shock test (mouse) after high doses probably cannot be considered to occur within the analgesic dose range. Inhibition of amphetamine toxicity in mice observed in doses near the hypnotic doses may be caused by non-specific effects. In vitro tests with isolated trachea or ileum of guinea pigs show that flupirtine possesses no or very weak antagonism against histamine-induced spasms. In spasms caused by barium chloride flupirtine shows a weak musculotropic-spasmolytic activity. Investigations on the circulatory system of dogs do not indicate any incompatibilities with flupirtine. No evidence of antiarrhythmic activity was found in rats. Flupirtine has no local anesthetic activity in mice but some weak effects on the cornea of rabbits. Like several other analgesics flupirtine shows in rats a reversible antidiuretic action including sodium and chloride retention which is of relatively short duration and is not observed in long-term studies in rats and dogs. In contrast to many stronger antiinflammatory compounds, flupirtine does not possess ulcerogenic activity in rats up to high doses. A minimal inhibition of intestinal motility (mouse) is observed only in doses higher than the analgesic effective doses. PMID- 4039153 TI - [Pharmacokinetics and biotransformation of the analgesic flupirtine in the rat and dog]. AB - Pharmacokinetics and biotransformation of 14C-labelled ethyl-N-[2-amino-6-(4 fluorophenylmethylamino)pyridin-3-yl]carbama te maleate (flupirtine maleate, D 9998 maleate) was studied in rats and dogs. The drug was rapidly and completely absorbed after peroral administration in both species. The kinetics of the plasma levels after intravenous administration show a short distribution phase followed by an elimination phase with half-lives between 2 and 3 h. Similar half-lives were observed after peroral administration: 2.2. h in the rat and 2.6 h in the dog. Renal excretion amounts to 20% (rat) and 36% (dog) after i.v. administration, and to 22% (rat) and 35% (dog) after p.o. administration. The major part of the dose is excreted via the feces. The drug is reversibly distributed to the tissues. Similar concentrations appear in the well perfused organs. A brain/plasma concentration ratio of greater than or equal to 1 was found and is a favourable prerequisite for a centrally acting analgesic. Insight in the biotransformation pathways of 14C-flupirtine maleate was obtained by structure determination of urinary metabolites. The urinary radioactivity of the rat consisted practically exclusively of p-fluoro-hippuric acid that is generated by an oxydative metabolic degradation of flupirtine. Dog urine, too, contains this metabolite, however, accompanied by the drug excreted unchanged and by a further metabolite structurally still very similar to flupirtine. The latter metabolite is formed via acetylation of an in vivo hydrolysis product of flupirtine and retains 1/4 of the analgesic potency of flupirtine. Regarding the patterns of excretion and of biotransformation the dog represents an intermediate between rat and man. PMID- 4039154 TI - [Pharmacokinetics and biotransformation of the analgesic flupirtine in humans]. AB - The pharmacokinetics of the analgesic flupirtine (ethyl-N-[2-amino-6-(4 fluorophenylmethylamino)pyridin-3-yl] carbamate, D 9998) were examined in healthy volunteers after a single intravenous, peroral and rectal dose. Plasma-and urine concentrations were analysed by a photometric procedure specific for flupirtine and its active metabolite D 13223. The bioavailability from the capsule amounted to 90%, from the suppository to 72.5%. Plasma half-life was 8.5-10.7 h. No significant accumulation of the plasma concentrations after multiple peroral administration was observed. After a peroral dose of 14C-flupirtine the radioactivity is predominantly excreted via the urine (72%). Two metabolites could be isolated from urine and their chemical structure determined. Together with the parent drug they explain 54% of the urinary radioactivity. The metabolite D 13223 that still has some analgesic activity is found in plasma, too. The portion of unchanged flupirtine amounts to 56-83% of the total plasma levels. PMID- 4039155 TI - [The effect of the analgesic flupirtine on automobile driving]. AB - The purpose of the present study was to investigate the effects on driving ability of the new analgesic ethyl-N-(2-amino-6-(4-fluor-phenylmethylamino) pyridin-3-yl) carbamate (flupirtine, D 9998) in comparison with pentazocine and placebo. Flupirtine was tested in a double blind cross-over experiment in 12 healthy volunteers using 7 different tests which are known to correspond to the most important aspects of driving ability. Subjects were given 3 consecutive doses of flupirtine of 100 mg each and tested following the first and third administration. The comparison drug pentazocine and placebo were administered in the same dosage regimen (a single dose of pentazocine amounting to 50 mg). Significant differences between flupirtine and placebo could not be detected. Following single dosage of pentazocine subjects more often reported a general feeling of discomfort, including nausea, dizziness and motion sickness, than was the case after administration of flupirtine. While single administration of pentazocine did not produce any significant differences from placebo, multiple administration resulted in both objective and subjective fatigue symptoms. It was concluded that flupirtine, in contrast to pentazocine, did not produce any impairment in driving ability in healthy volunteers. PMID- 4039156 TI - Evaluation of epileptic dogs as an animal model of human epilepsy. AB - In 126 epileptic dogs with spontaneously recurring generalized tonic-clonic (grand mal) seizures, epidemiological aspects and the efficacy of chronic oral treatment with common antiepileptic drugs were studied. Furthermore, the pharmacokinetics of antiepileptic drugs in dogs was compared with the values known for man. As in man, idiopathic epilepsy appeared to be more common than symptomatic epilepsy in dogs. There was a preponderance of male vs. female animals. When the breeds of the epileptic dogs were compared to the distribution of breeds in the hospital population, breed-related differences in the prevalence of epilepsy were found. The highest prevalence was seen in Cocker spaniels, Miniature schnauzers, Collies and Bassets. The total prevalence of dogs with epilepsy was 0.55%. Comparison of pharmacokinetics of antiepileptic drugs showed that some drugs were suited for maintenance therapy in dogs (primidone, phenobarbital, ethosuximide, trimethadione) whereas others appeared not to be ideally suited because of their short half-lives (phenytoin, carbamazepine, valproic acid, diazepam, clonazepam, nitrazepam). This was confirmed by the evaluation of antiepileptic drug efficacy in epileptic dogs. 46 dogs were treated with primidone at daily doses of 14-104 mg/kg for 6-60 months. During medication with primidone, effective plasma levels of its metabolite phenobarbital could be maintained. Complete control of seizures or a reduction of seizure frequency by at least 75% was achieved in 39% of the dogs at phenobarbital concentrations of 5 49 micrograms/ml. Similar figures were obtained during chronic treatment with phenobarbital at daily doses of 2.5-13 mg/kg.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4039157 TI - [The effect on oxidative metabolism in brain, liver and heart muscle homogenates of peptide derivatives and calf blood dialysates]. AB - Three peptide preparations, derived from different proteins, and one protein free extract, produced by dialysis of calf blood, were tested. Typical effects of the individual preparations on oxidative metabolism could be shown. A comparable high stimulation of oxygen consumption of brain homogenates by 117 to 165% was measured after application of the peptide derivatives. One of them, the peptide enriched derivative, caused a high and not organ specific stimulation, increasing the oxygen consumption of brain, liver and heart muscle by 165, 203 and 202%, respectively, thus exceeding the effects of the other tested preparations. Extracts of calf blood, which showed maximal stimulation in liver homogenate (98%), led to rather small effects in brain homogenate (51%) compared with those induced by the peptide derivatives. PMID- 4039158 TI - [The phagocytosis activity of India ink in the isolated rat liver perfused with piracetam]. AB - The activity of the reticulohistiocytic system of the isolated perfused liver was measured under the influence of piracetam (Nootrop). Also the parameters of liver function under the influence of piracetam were determined. If the energetical properties were not optimal it was shown that the phagocytic activity increased under the influence of piracetam. Also the parameters of liver cell function increased. Under optimal energetic properties there was no changing of the phagocytic activity but the liver cell parameters decreased. PMID- 4039159 TI - The respiratory response to stimulation of juxta-pulmonary capillary receptors in the non-anesthetized cat. AB - To avoid the modifying influence of general anesthesia on vagal control of respiration, we investigated the effect of phenyldiguanide (PDG), a drug known to stimulate juxta-pulmonary capillary ("J") receptors, in the non-anesthetized, unrestrained cat and recorded EEG, eye movements, neck muscle EMG, EKG and respiratory movements. The response to bolus injection of PDG into the right atrium was qualitatively similar to the one seen in cats under anesthesia, consisting of bradycardia and apnea followed by rapid shallow breathing (RSB). The injection-response latencies ranged from 1.5 to 3 s, indicating that the effect originated on the venous side of the cardiopulmonary region. Vagal block with lidocaine, which was applied via external tubings feeding into implanted vagal "sleeves", abolished the responses to PDG, demonstrating their dependence on vagal mediation. Atropine blocked the bradycardia but did not affect the apnea. All doses of PDG which affected respiration uniformly produced initial apnea, whose duration, in any given animal and trial session, exhibited a consistent dose-response relationship. Slow injections also produced apnea. RSB following the apnea was variable in frequency and amplitude of excursions and in its overall duration, and failed to reveal a dose-response relationship. Apnea lasted significantly longer when injections were made during slow wave sleep or REM sleep as compared to injections given during wakefulness or drowsiness. Arousal from all states of sleep occurred simultaneously with the onset of apnea and bradycardia and was also dependent on the vagi. Spontaneous awakening from sleep, by contrast, was always associated with an increase in breathing.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4039160 TI - Cardiac effects of fenoterol hydrobromide on newborn versus adult rats. AB - The toxicity of fenoterol hydrobromide, a beta-adrenoceptor stimulant, was studied in newborn and adult SD-rats dosed with 0 (control), 2.5, 75 and 600 mg/kg/day by gavage for 35 days. 600 mg/kg was lethal for both age groups: newborn rats died either from gastro-intestinal disorders during the lactation period or from underweight and cachexia immediately after weaning. Adult rats which died from 600 mg/kg showed extended myocardial scars. No substance-related myocardial lesions were observed in newborn rats killed terminally, whereas adult rats had a dose-dependent increase in heart weights, at 600 mg/kg also extended myocardial scars. PMID- 4039162 TI - [Microbiological in-process control in drug manufacture]. AB - The microbiological quality required of all pharmaceutical preparations necessitates raw materials and packing materials in perfect condition, and also attention to conditions of hygiene. It is also necessary to be in control of sources of contamination such as water, air, rooms, technical equipment and personnel. The paper examines the following points; the danger of contamination presented by the above sources, which conditions or recommendations exist for microbiological quality, and which methods are available for microbiological quality control within the framework of the production of drugs. PMID- 4039161 TI - The effect of pH on alkaline phosphatase activity in serum of the rat and other species. AB - Contrary to other species, optimum pH of alkaline phosphatase (alk.P.) activity was 9.6 in fed male rats of all age groups studies. In 3- or 6-week-old fasted rats, the optimum pH shifted to 9.8-10.0. This shifting of pH did not occur in 11 week-old rats. Heating to 56 degrees C for 10 min shifted the optimum pH in 3 week-old rats to 9.0, in 6-week-old rats to 9.0-9.4, but no change occurred in 11 week-old rats. In other species (mouse, rabbit, and man), the optimum pH was 10.0 10.2, and was not influenced by fasting or heating. PMID- 4039163 TI - [Synthesis of anticholinergically active N-alkylnorscopolamines and their quaternary salts with special consideration of the bronchospasmolytic (-)-N ethylnorscopolamine methobromide (Ba 253 BR)]. AB - The synthesis of anticholinergic N-alkylnorscopolamines and their quaternary salts, especially the synthesis of (-)-N-ethylnorscopolamin methobromide (Ba 253 BR), is reported. (-)-N-Ethylnorscopolamine methobromide differs from the stereoisomeric (-)-N-ethylscopolammonium bromide not only by its physico chemical, but also by its pharmacological properties. (-)-N-Ethylnorscopolamine methobromide represents an anticholinergic bronchodilator with long duration of action. PMID- 4039164 TI - [Diminished increase in body length in rats as an indicator of toxic injuries]. AB - In four subchronic and three chronic toxicity studies in rats, in which the application of pharmacologically active substances led to a reduction in body weight development, the lengths of the animals were also measured. It could be shown that a lower body weight gain was always accompanied by a reduction in body length increase. With increasing doses or higher toxicity the within-group variations of individual values were smaller and the correlation between body weight and length of the rats was generally greater. PMID- 4039165 TI - [Metabolism of beclobrate in rat and man]. AB - The major pathway of biotransformation of beclobrate [(2-[4-[(4 chlorophenyl)methyl]phenoxy]-2-methylbutyric acid ethyl ester] is the ester cleavage to beclobrinic acid (M1), which is eliminated as glucuronide. Subsequent metabolic attack is occurring via oxidation of the methylene bridge to the carbinol (M2) as well as to the benzophenone (M3). The p-chloro substituted phenyl ring is oxidated via a postulated arene oxide to the 2'- and 3'-phenol metabolites (M5 and M6) and to the trans-2',3'-dihydrodiol (M4). Except M4, all metabolites are eliminated exclusively as glucuronides. PMID- 4039166 TI - [Biochemical studies with oxitropium bromide. 1. Pharmacokinetics and metabolism in the rat and dog]. AB - The bronchospasmolytic drug (8r)-6 beta, 7 beta-epoxy-8-ethyl-3 alpha-[(-) tropoyloxy]-1 alpha H, 5 alpha H-tropanium bromide (oxitropium bromide, Ba 253 BR, Ventilat) was tested pharmacokinetically as a 14C labelled substance in rats and dogs. Following oral administration low concentrations of radioactivity persisting over several hours were measured in the blood of dogs and rats. The active ingredient which can be separated from the metabolites by thin layer chromatography and quantified via the radioactivity reaches a maximum in the rat plasma after 1 to 2 h; it is then eliminated from the blood with a half-life of approx. 4 h. Following intravenous administration the radioactivity measured directly (active ingredient + metabolites) is distributed rapidly into the tissue of the rat and the dog. The distribution phase is followed by a relatively fast elimination phase ending in the terminal elimination phase approx. 1 h after administration. Rats and dogs eliminate the radioactivity mainly with the feces after oral administration, whereas following intravenous administration the rat eliminates about half with the feces and half via the kidneys. Biliary excretion of the rat is 12% after oral and 14% after intravenous administration. The rat absorbs 14% and the dog 28% of dose. Five metabolites have been demonstrated in the urine of the rat and the dog. Metabolism takes place exclusively in the tropaic acid part of the molecule and by hydrolysis of the compound. PMID- 4039167 TI - [Biochemical studies with oxitropium bromide. 2. Pharmacokinetics and metabolism in humans]. AB - The present paper reports on the human pharmacokinetics of (8r)-6 beta, 7 beta epoxy-8-ethyl-3 alpha-/(-)-tropoyloxy/-1 alpha H, 5 alpha H-tropanium bromide (oxitropium bromide, Ba 253 BR, Ventilat) after intravenous and oral administration as well as following inhalation. The 14C-labelled substance was used. The concentrations of radioactivity measured in the plasma after i.v. administration show a biphasic course, a rapid alpha phase and a terminal phase (t 1/2 = 1.5 h). Once the alpha phase has passed the radioactivity concentrations measured after i.v. administration of 1 mg are comparable with those after 20 mg administered orally. The concentration course after inhalation corresponds essentially to the course after oral administration of lower doses. The cumulative renal excretion of the radioactivity is 68-78% for i.v. administration, 13% for oral administration, and 10% for inhalation. 7% (i.v.), 77% (p.o.) and 88% (inhalation) is excreted in the faeces. Oxitropium bromide is rapidly hydrolysed after oral administration. As little as 4 h later only 2-3% of intact active ingredient is found, whereas there is 85% of the hydrolysed product in the urine. A similar distribution pattern is observed in urine samples taken later. Some other metabolites are also recorded in minimal quantities. After i.v. administration, too, the hydrolysed product is excreted as the main component. PMID- 4039168 TI - Cardiovascular effects of the positive inotropic agents pimobendan and sulmazole in vivo. AB - The effects of the cardiotonics sulmazole (AR-L 115 BS, Vardax) and pimobendan (UD-CG 115 BS) on cardiac contractility, heart rate and diastolic blood pressure were investigated in vivo in pithed guinea pigs, anaesthesized cats and conscious dogs. UD-CG 115 BS proved to be about 5-6 times more active than AR-L 115 BS as a positive inotropic agent in pithed guinea pigs and anaesthetized cats. The hypotensive effects of AR-L 115 BS and UD-CG 115 BS were comparable in pithed guinea pigs whereas UD-CG 115 BS showed stronger hypotensive effects than AR-L 115 BS in anaesthetized cats. A dose of 5 mg/kg of AR-L 115 BS evoked positive inotropic effects during 4-5 h after oral administration to conscious dogs. UD-CG 115 BS (1 mg/kg p.o.) induced a strong increase in LV-dp/dtmax in conscious dogs. These positive inotropic effects lasted for more than 8 h with negligible effects on diastolic blood pressure and heart rate. PMID- 4039169 TI - Calcium antagonists--terminology, classification and comparison. AB - A survey is given of the terminology and classification of calcium antagonistic drugs. Calcium entry blockers are defined as drugs of which the major effect is the selective blockade of the slow inward current across the membrane, also under physiological conditions. Calcium overload blockers are defined as compounds which prevent the overloading of the cell with calcium under pathological, ischemic conditions. Both types of drugs should be considered as examples of different principles, although compounds which possess both properties simultaneously are known to exist. Furthermore, a comparison is made between the various groups of calcium entry blockers and calcium overload blockers, with respect to their chemical, pharmacological and therapeutic properties, including their organ specificity. PMID- 4039170 TI - Investigations into the bradycardic action of indoramin. AB - Indoramin is a selective alpha 1-antagonist which reduces blood pressure without reflex tachycardia and can cause a bradycardia. The direct bradycardic effect of indoramin was investigated in various isolated cardiac preparations as well as in the intact cat. In isolated guinea-pig atria indoramin reduced spontaneous atrial rate in concentrations similar to those that reduced maximal driving frequency but smaller than those reducing contractility (EC30 = 0.9, 1.3 and 5.2 micrograms/ml, respectively). In the isolated perfused electrically driven (2.5 Hz) guinea-pig heart, indoramin 1 microgram/ml mainly increased ST interval with no effect on QRS interval, higher concentrations (3 micrograms/ml) also increased the QRS interval. In anaesthetized cats indoramin 6 mg/kg i.v. reduced blood pressure and heart rate (increased cycle length), increased the ST interval and effective refractory period (measured by electrical stimuli from the right ventricle) but had little or no effect on the QRS interval and the diastolic stimulation threshold. With the 10 mg/kg dose the latter two parameters were increased. Analogous experiments with the antiarrhythmic drug mexiletine (class I) showed little changes in cycle length, effective refractory period and the ST interval, however, there was a marked increase in diastolic threshold. DL sotalol, which as well as having a beta-adrenoceptor blocking action, also prolongs action potential duration (class III antiarrhythmic activity), had the same cardiac profile as indoramin. For both indoramin and sotalol a significant positive correlation was shown between increase in cycle length and increase in effective refractory period. It is suggested that indoramin exerts class III antiarrhythmic activity and that this property is responsible for the bradycardic action of the drug which is seen in doses that already markedly reduce blood pressure. In higher doses or concentrations indoramin also exerts class I antiarrhythmic activity which, however, does not contribute to the bradycardic effect. PMID- 4039171 TI - Uterine relaxation by clenbuterol and fenoterol in conscious rats. AB - The uterine relaxant activity of clenbuterol and fenoterol was compared in conscious non-pregnant rats with chronically implanted uterine catheters. 0.001 0.020 mg/kg clenbuterol i.v. significantly reduced uterine motility, duration of action exceeded the observation period of 30 min. After oral administration nearly identical doses were needed for comparable effects. Following intravenous administration, 0.005 mg/kg fenoterol induced uterine relaxation, but in contrast to clenbuterol, duration of action was short. After oral administration relatively high doses of 1 and 5 mg/kg were needed for reduction of uterine motility. These results may encourage the use of clenbuterol in obstetric practice. They enlarge the basis for the evaluation of pharmacological findings obtained with fenoterol and clenbuterol. PMID- 4039172 TI - Synthesis and antibacterial activity of pyrimidinylureidopenicillins. AB - The 6R-[(R)-2-[3-[5-pyrimidinyl]ureido]-2-(4-hydroxyphenyl) acetamido] penicillanic acids (10), prepared by two synthetic routes, exhibit broad antimicrobial activity against Gram-positive and Gram-negative bacteria. Their structure activity relationships are discussed. 6R-[(R)-2-[3-[2-(p Aminosulfonyl)anilino-4-hydroxy-5-pyrimidinyl] ureido]-2-(4 hydroxyphenyl)acetamido]-penicillanic acid, sodium salt (VX-VC 43, 10m), the most active compound, shows very low MIC (minimal inhibitory concentration) values against clinically important Gram-negative bacteria, primarily Pseudomonas aeruginosa. PMID- 4039173 TI - Inhibition of sympathetic nervous system by mexiletine, an antiarrhythmic agent, and its antagonism against ouabain. AB - The effects of mexiletine on the sympathetic nervous system and the antiarrhythmic action were studied and compared with those of lidocaine. In isolated blood vessels, mexiletine inhibited the contractile responses to nicotine, tyramine and electrical transmural stimulation, but did not affect the contractile responses to exogenous norepinephrine and KCl. Lidocaine also inhibited the contractile responses to nicotine and electrical transmural stimulation, but such an inhibitory activity was weaker than that of mexiletine. Lidocaine did not affect the contraction induced by tyramine and enhanced significantly contractile responses to exogenous norepinephrine and KCl. Mexiletine and lidocaine inhibited the release of 3H-norepinephrine from the isolated rabbit pulmonary artery induced by transmural electrical stimulation. Mexiletine increased the dose of ouabain required for the occurrence of arrhythmia and cardiac arrest. These effects of mexiletine did not occur after reserpine. Though lidocaine increased the dose of ouabain required for cardiac arrest, the development of arrhythmia was not prevented. The increase in the dose of ouabain required for cardiac arrest induced by lidocaine was not affected by reserpine. On the other hand, mexiletine and lidocaine prevented the epinephrine induced arrhythmia. These results suggested that the antagonism of mexiletine against ouabain may be due not only to the previously reported quinidine-like direct action on the myocardium, but also partially to the inhibitory action on releasing norepinephrine from the sympathetic nerve terminals. PMID- 4039174 TI - Disposition of 3H-fenoterol after inhalation in rats. AB - The time course of radioactivity in blood was compared following oral administration, intratracheal instillation and inhalation, respectively, of 3H fenoterol hydrobromide in rats. Also the tissue levels after inhalation were measured. A small peak of the blood level appeared within 10 min after inhalation followed by a second larger peak. The peak time in the first phase corresponded with that after intratracheal instillation, suggesting that this phase should be attributed to local absorption in the lung. The second peak corresponded with that after oral administration, suggesting that a large proportion of the drug taken in by the animal after inhalation was swallowed and absorbed in the gastrointestinal tract. A direct measurement of radioactivity in tissue samples of the lung, trachea, oesophagus, stomach and small intestine demonstrated clearly the above accounts. PMID- 4039175 TI - Immunoassay for the quantitation of human leukocyte interferon. AB - A sensitive nonradioactive immunoassay based on monoclonal antibodies was developed. A number of monoclonal hybridomas secreting antibodies against human leukocyte interferon (IFN alpha) were generated using mice immunized with purified lymphoblastoid IFN. Although the binding of antibody to IFN alpha was used as one criterium of selection, all antibodies found can neutralize its antiviral activity. A pair of antibodies binding to different regions of IFN alpha was identified. These were incorporated into sensitive sandwich assays of IFN alpha. A microtiter plate assay - using horse radish peroxidase as marker enzyme - is able to detect IFN alpha at a concentration of 30 IU/ml within 5 h. An overnight tube assay can detect approximately 30 pg IFN alpha 2 or 3 IU per ml solution. The 5-h ELISA (enzyme-linked immunosorbent assay) is well suited for the monitoring of the recovery of rIFN alpha from recombinant organism, during purification and refinement of the protein to a therapeutic drug. PMID- 4039176 TI - Investigation into the inotropic mechanisms of sulmazole. AB - A calcium ionophorous action of sulmazole (AR-L 115 BS, Vardax) as a cause of its positive inotropic action could be excluded because the drug did not carry calcium ions across a lipid barrier. Sulmazole at concentrations of 1-10 mmol/l induced contractures in the isolated rat diaphragma as effectively as caffeine. Both drugs also gave rise to contracture in the absence of extracellular calcium ions indicating the liberation of calcium from intracellular sites. Sulmazole precipitated contracture anew in partially relaxed atria of the guinea pig after long-standing (1 h) withdrawal of extracellular sodium. This effect of sulmazole was concentration-dependent (0.1-1 mmol/l), as was that of caffeine (1-10 mmol/l) in this preparation. As the concentration-response curves of the drugs were parallel and were shifted by procaine in a parallel manner to the right, this action of sulmazole can be described as "caffeine-like". Sulmazole (0.033-1 mmol/l) displayed its positive inotropic action particularly at the lower rates of atrial contraction and inhibited the effect of poststimulatory potentiation. In the range of higher concentrations and rates of contraction, increases in diastolic tension occurred. In atria with a steady-state contractility being almost completely suppressed by nifedipine (3.3 mumol/l), sulmazole (0.33-1 mmol/l) restored contractile force while caffeine (2-8 mmol/l) did not. These results show that the positive inotropic action is neither due to a "caffeine like" effect nor related to the slow inward current.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4039177 TI - The influence of metabolic degradation on the blood pressure lowering effect of clonidine in rabbits after different routes of administration. AB - In rabbits, clonidine (200 micrograms/kg) exerted no blood pressure lowering effect after oral administration contrary to the strong decrease in blood pressure after i.v. injection. This surprising effect induced experiments on metabolic degradation of clonidine in the rabbit. After oral administration 14C clonidine was rapidly almost totally metabolised and only minimal concentrations could be detected in the brain. In the urine (24-h collection) no clonidine was detected after oral dosing. In contrast, 15 min after i.v. injection 30% of radioactivity was unchanged clonidine in the plasma. In the brain 70% of the radioactivity during the first 2 h was clonidine. In accord with this, in the urine 22% of the dose administered was excreted as clonidine. From these experiments it is concluded that predominantly unchanged clonidine penetrates the blood-brain barrier. So the lack of effect after oral clonidine depends on the too low concentration of clonidine in the brain. To assess the pharmacological activity of clonidine metabolites identified in rabbit and other species including man, seven different compounds were injected to rabbits either systemically (i.v.) or intracisternally (i.c.i). Only p-hydroxy-clonidine hydrobromide (St 666) induced weak blood pressure decreases after i.v. and strong ones after i.ci. injection, but to a lesser extent than clonidine itself. PMID- 4039178 TI - Relaxant effects on tracheal and ileal smooth muscles of the guinea pig. AB - The effects of volatile oils of 22 plants from 11 different families and of some of their constituents on tracheal and ileal smooth muscles were investigated. The results were compared with the relaxant effects of catecholamines and phosphodiesterase inhibitors. All of the oils had relaxant effects on the tracheal smooth muscle, the most potent were angelica root, clove, elecampane root, basil and balm leaves oil. 16 oils inhibited the phasic contractions of the ileal myenteric plexus-longitudinal muscle preparation, the most potent were elecampane root, clove, thyme, balm leaves and angelica root oil. 2 oils (anise and fennel) increased the phasic contractions, and 4 oils (bitter orange, caraway, mace, pepper) produced a marked increase in resting force (i.e. contracture). In regard to the relaxant effects, most of the 16 oils were more potent on the ileal than on the tracheal muscle. However, a small group of 4 oils (angelica root, clove, basil, black caraway) had a higher relaxant effect on the tracheal than on the ileal muscle. This was also found to be the case with eugenol, eugenol acetate and cinnamic aldehyde as well as with isoprenaline and phosphodiesterase inhibitors. PMID- 4039179 TI - Radioimmunological determination of fenoterol. Part I: Theoretical fundamentals. AB - A general solution is given for the system of equations describing coupled mass equilibria having m antibodies with one binding site, or with several mutually independent binding sites of equal intrinsic affinity (immunoglobulin (Ig) G antibodies) and n monovalent antigens. Based on this a formula is given with which it is possible to calculate the minimum association constant of the antibody and the minimum specific radioactivity of the tracer in a radioimmunoassay when the detection limit is given and the assay conditions are established. The model m = 2 and n = 4 describes the behaviour of a system which is based on a mixture of stereoselective antibodies and a racemic tracer. The effect of the enantiomer ratio of an optically active ligand on this system is demonstrated. PMID- 4039180 TI - Inhibition of potassium-induced contracture of the isolated rat aorta by amiloride. AB - Potassium contractures of helically cut strips of rat aorta were recorded isometrically. Contractures induced by KCl 40 mmol/l were decreased dose dependently by amiloride (1.7 X 10(-5) to 1.4 X 10(-4) mol/l) added to the bath 10 min before the depolarization. Ouabain (10(-3) mol/l) antagonized this effect. Contractures induced by using, instead of normal Krebs solution, a solution in which potassium was replaced by sodium (Krebs potassium) were also decreased dose dependently by amiloride, but the slope of the linear log dose-effect curve line was steeper. When arteries were incubated in a solution deprived of sodium and calcium (isotonicity maintained by choline), the intensity of consecutive contractures by Krebs potassium decreased progressively. Incubation in a normal Krebs solution restored the normal contractures; amiloride added at the same time prevented this restoration. These findings are in agreement with the assumption that sodium-calcium exchange plays an important part in the contracture of vascular smooth muscles. PMID- 4039181 TI - Structure-activity relationship in clonidine-like 2,3-disubstituted 2-aryl-imino imidazolidines. AB - In anaesthetized rabbits the hypotensive activity of a group of 2,3-disubstituted 2-aryl-imino-imidazolidines was estimated. Compounds with 3-bromo substituents at the phenyl moiety of the molecule are more than or as active as clonidine. Correlations between blood pressure lowering effect and lipophilicity, maximum alpha-adrenergic effects (alpha E') and -log ED50 (pD2') of blood pressure increase in spinalized rats and pKA were calculated. The results show a positive linear correlation between as well partition coefficient as alpha E' and hypotension. The relationship between pD2' and hypotensive. effect is less prominent. pKA seems to have no influence on the blood pressure effects of these compounds. PMID- 4039182 TI - Effects of drugs on schedule-controlled running of mice in a circular runway. AB - Partially food deprived mice ran in a 1-m circular runway. Every 30 circuits, diluted evaporated milk was delivered. Under control conditions mice averaged 0.18 circuits/s for 1 h. The rate was reduced to 0.11 circuits/s 1 h after gavage of Tylose (cellulose derivative) vehicle. Amphetamine, chlordiazepoxide and pentobarbital increased the rate of responding over some dose range, but chlorpromazine, clozapine, imipramine and morphine caused only decreases in responding at effective dose levels. The results are generally similar to reports of effects of the drugs on responses of much briefer duration occurring at similar rates. PMID- 4039183 TI - [Pharmacology of the bronchospasmolytic oxitropium bromide]. AB - The anticholinergic substance (8r)-6 beta, 7 beta-epoxy-8-ethyl-3 alpha-[(-) tropoyloxyl]-1 alpha H, 5 alpha H-tropanium bromide (oxitropium bromide, Ba 253 BR, Ventilat) is a competitive antagonist of acetylcholine. In vitro, it is many times as effective as atropine. In vivo, oxitropium bromide, following i.v. administration, is also more effective than atropine. Due to its quaternary structure, a central anticholinergic effect cannot be demonstrated. Furthermore, poor enteral resorption is to be expected. Locally administered, as an aqueous aerosol, the effect of the substance is distinctly greater than that of atropine, both in potency and duration of action. This is also true when administered by metered-dose inhaler compared with ipratropium bromide. As, following aerosol administration, the margin between major effect and the most sensitive side effect is in the ratio 1 : 100, side-effects are unlikely even with marked inhalational overdosage. Oxitropium bromide can be described, therefore, as a preparation free of side-effects which represents in prophylactic use in many cases of obstructive airway disease, an alternative to beta-mimetics and xanthine derivatives. PMID- 4039184 TI - Pharmacokinetics of oral sustained release clonidine in humans. AB - Tablet cores of clonidine (Catapres) showing varying rates of in vitro dissolution were administered in a crossover study with intravenous clonidine to determine the rate of absorption into the systemic circulation in humans. Excellent bioavailability (0.87-0.96) was obtained in all 12 subjects for each of the formulations. When peak concentration and time to peak are compared for the standard immediate release cores and the cores designed to be slowly dissolving there was a significant difference (p less than 0.05). Absorption rate plots for each formulation in each subject were obtained using the Loo-Riegelman procedure of comparing the oral pharmacokinetic profile with the intravenous profile. As the release from the cores were formulated to be slower, the in vivo absorption rate of clonidine approached zero order input. Incorporating combinations of sustained release and immediate release cores into a capsule (Perlonget) gave predictable absorption rates, permitting the formulation scientist to control the plasma levels obtained from oral dosing of clonidine. The intravenous pharmacokinetics of clonidine after a 0.2 mg infusion followed a tri-exponential decline with a final phase half-life of 13.6 h (harmonic mean). Following the intravenous infusion 42.3% of the dose was excreted unchanged in the urine with a renal clearance of 10.05 +/- 0.65 1/h (167 ml/min). PMID- 4039185 TI - [Convulsive crises in the newborn infant. Study of 100 patients in an emergency service]. PMID- 4039186 TI - Neonatal pulmonary haemorrhage, birthweight, gestational age and intrauterine growth. AB - The relation between neonatal pulmonary haemorrhage and its underlying cause was studied by reviewing the clinical data and necropsy records of 315 newborn babies who had died between day 0 and 31 of life. Necropsy revealed massive and focal pulmonary haemorrhage in 6.9% and 19.3% of the infants, respectively. It has been concluded that pulmonary haemorrhage is a complication of various neonatal diseases related to hypoxia and/or infection, which occur in preterm infants with a much higher frequency than in term babies. Among patients with pulmonary haemorrhage, males and low birthweight babies predominated. PMID- 4039187 TI - Progression of hypertrophic cardiomyopathy. A cross sectional echocardiographic study. AB - The progression of hypertrophy was studied in 39 patients with hypertrophic cardiomyopathy by echocardiography at follow up from January 1979 to September 1983 (mean follow up 42 months). Thirty two patients were treated medically and 11 had had a septal myotomy-myectomy. Progression of the hypertrophy was noted in four patients treated with propranolol. An additional region in the left ventricular long axis plane was affected in two, extending to the apical region in one and to the basal region in the other, and an additional segment in the left ventricular short axis plane in two extending from the septum into the free wall. The electrocardiograms of these four patients showed a significant increase in QRS voltages (Sokolow-Lyon index increase greater than 10 mm) and of the Romhilt-Estes score (increase greater than or equal to 3 points) in two, development of a left bundle branch block in one, and no change in one. Progression of hypertrophy was seen in none of the 11 patients treated with myotomy-myectomy. Thus echocardiography accurately detects the progression of hypertrophy in patients with hypertrophic cardiomyopathy, which may be prevented by septal myotomy-myectomy. PMID- 4039188 TI - Improved survival with amiodarone in patients with hypertrophic cardiomyopathy and ventricular tachycardia. AB - The effect of amiodarone on survival was assessed in patients with hypertrophic cardiomyopathy and ventricular tachycardia in a drug trial with historical controls. During 1976 and 1977, 24 hour (seven) or 48 hour (79) electrocardiographic monitoring was performed in 86 consecutive patients; 24 had ventricular tachycardia and received conventional antiarrhythmic agents. Nineteen clinical, echocardiographic, and haemodynamic features were assessed. Seven patients died suddenly during follow up of three years; of these, five had continued to have ventricular tachycardia and two had no documented ventricular tachycardia. During 1978 and 1979, ventricular tachycardia was detected during 48 hour electrocardiographic monitoring in 21 of the next 82 consecutive patients with hypertrophic cardiomyopathy. They received amiodarone (150-400 mg/day, median 300); ventricular tachycardia was suppressed in all during repeat 48 hour electrocardiographic examination. Two patients died suddenly during a three year follow up, but neither belonged to the amiodarone treated group with ventricular tachycardia. The clinical and haemodynamic variables were similar in patients taking amiodarone and conventional agents. The fact that control of ventricular arrhythmia with amiodarone is significantly associated with improved survival suggests that amiodarone may prevent sudden death in patients with hypertrophic cardiomyopathy and ventricular tachycardia. PMID- 4039189 TI - Pharmacokinetics of aztreonam in elderly male volunteers. AB - The pharmacokinetics of aztreonam were studied in 12 healthy male volunteers aged 65 to 75 years who received 1 g of the antibiotic intravenously. Data were fitted to a two-compartment open model to yield the following parameters: t 1/2, lambda 1, 0.15 h; t 1/2,z, 2.06 h; area under the 24-h serum concentration-time curve, 231.8 micrograms ml-1 h; Cmax, 120.1 micrograms/ml; V1 area, 0.16 l/kg; and serum clearance, 0.94 ml min-1 kg. Twenty-four hour urinary elimination reached 63.1% of dose as aztreonam and 3.1% as the open ring metabolite SQ 26,992. These data were similar to those obtained for healthy males aged 18 to 35 years. Thus, age per se is not a major therapeutic consideration in treating elderly patients, and other factors, primarily the parameters of renal function, should serve as the basis for any dose reduction. PMID- 4039191 TI - Asymmetric transport of a fluorescent glucose analogue by human erythrocytes. AB - A fluorescent glucose analogue, 6-deoxy-N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl) aminoglucose (NBDG), was synthesized and its interactions with the hexose transport system of the human red blood cell were investigated. NBDG entry is inhibited by increasing concentrations of D-glucose (Ki = 2 mM). However, NBDG exit is unaffected by D-glucose in red blood cells. Cytochalasin B was found to inhibit both NBDG entry and exit. NBDG accumulates in the red blood cell above the theoretical equilibrium concentration. Accumulation of NBDG is temperature sensitive and is due to the binding of NBDG to some intracellular substance. The binding of NBDG to purified hemoglobin suggests that accumulation of NBDG by erythrocytes is due to the intracellular binding of NBDG to hemoglobin. NBDG does not accumulate in pink erythrocyte ghosts, while its rate of uptake is still inhibited by D-glucose and cytochalasin B. Although there was no apparent D glucose inhibition of NBDG exit by intact red blood cells, D-glucose was able to inhibit NBDG exit by pink erythrocyte ghosts. The differing properties of NBDG influx and efflux support the interpretation that the hexose transport system of the human red blood cell appears asymmetric although it may be intrinsically symmetric. PMID- 4039190 TI - Prolonged protective effects following propranolol withdrawal against isoproterenol-induced myocardial infarction in normotensive and hypertensive rats. AB - Young adult, male and female, normotensive Sprague-Dawley (S-D) and spontaneously hypertensive rats (SHR) were injected with propranolol three times daily for 3 weeks. None of the animals manifested signs of withdrawal when the injections were terminated. Seven days later, the animals were challenged with a dose of isoproterenol which would produce massive myocardial infarction and 50-60% mortality in non-treated animals. The propranolol pretreatment caused marked tranquilizing and blood pressure lowering effects in SHR exclusively. Despite the 7-day propranolol withdrawal period, very few animals died and myocardial damage was minimal. However, blood pressure levels dropped to shock-like levels, blood CPK and LDH levels showed dynamic increases, there was marked hypertriglyceridaemia, and plasma corticosterone rose to supranormal levels. Microscopically, the hearts of the propranolol pretreated animals showed little evidence of necrosis but the SHR hearts manifested large atrial and ventricular thrombi. It is suggested that in the rat, propranolol treatment causes positive myocardial protective effects mediated through hormonal and metabolic changes and propranolol withdrawal does not lead to hypersensitivity to catecholamines. In fact, the beta-blocking effects of propranolol remain effective for some time after withdrawal. PMID- 4039192 TI - Interaction of platelet factor 4 with human platelets. AB - Human washed resting platelets bound 125I-labeled platelet factor 4 in a reaction which was saturable and approached equilibrium within 15-30 min. Scatchard plot analysis of the binding isotherms suggested a single class of specific binding sites. Excess of unlabeled protein and low- and high-affinity heparin competed for platelet factor 4 binding sites on the platelet surface and caused a partial displacement of this molecule. Anti-platelet factor 4 Fab fragments caused inhibition of binding of 125I-platelet factor 4 to platelets. Most of the labeled platelet factor 4 which was bound to intact platelets was recovered in the Triton X-100-insoluble cytoskeletal fraction prepared from the same platelets after their stimulation by thrombin. The association with the cytoskeleton was inhibited by anti-platelet factor 4 Fab fragments and by low-affinity heparin. Anti-platelet factor 4 125I-labeled Fab fragments bound to resting platelets, and this binding was greatly increased following platelet stimulation with thrombin. This suggested that endogenously secreted platelet factor 4 also binds to the platelet surface. No significant binding to platelets of 125I-labeled beta thromboglobulin and 125I-labeled anti-beta-thromboglobulin Fab fragments was observed. Fab fragments of monospecific anti-human platelet factor 4 antibody raised in rabbits inhibited platelet aggregation and secretion induced by low concentrations of thrombin. Fab fragments of anti-beta-thromboglobulin antibody had no inhibitory effect. We suggest that the binding of alpha-granule-derived platelet factor 4 to the specific sites on the surface of platelets may modulate platelet aggregation and secretion induced by low levels of platelet agonists. PMID- 4039194 TI - Effect of nutrition on tissue carnitine concentrations in infants of different gestational ages. AB - To investigate the effect of nutrition on tissue carnitine concentrations in infants of different gestational ages, specimens of muscle, heart, liver and kidney obtained at autopsy from 62 infants were analyzed for total acid-soluble carnitine content. Immature infants had smaller carnitine tissue reserves than term infants. Parenterally alimented premature infants (greater than 10 days old) had lower carnitine levels in heart, liver and kidney than those dying within 24 h after birth. Infants who received oral or intravenous carnitine had larger carnitine tissue reserves than those who did not. These data suggest that both gestational age and exogenous carnitine supply affect tissue carnitine reserves. PMID- 4039193 TI - [The state of brain mitochondrial membranes in stress and its correction with drugs]. AB - It is evident that the reconstruction of mitochondrial membranes is the foundation of bioenergetic damage of the brain. It leads to their structure damage and consequently to the functional damage. The correction of this state is possible with the help of nicotine acid derivatives. PMID- 4039195 TI - Changes in serum concentration and ovarian content of 5 alpha-androstane-3 alpha,17 beta-diol in the female rat approaching first ovulation. AB - Concentrations of 5 alpha-androstane-3 alpha,17 beta-diol (3 alpha-diol) in serum were estimated in rats bled once during a 10-day period preceding first ovulation; ovarian contents of 3 alpha-diol were estimated over the same period. Serum values of 3 alpha-diol, measured at 1100 h, showed a significant decrease towards first ovulation; there was good correlation (r = 0.78; n = 10) between mean serum and ovarian concentrations. In 33-day-old rats no significant difference was found in serum concentrations measured at either 1100 or at 1500 h. However at first proestrus, significantly elevated serum and ovarian concentrations of 3 alpha-diol were found between 1400 and 2100 h as compared to those at 1100 h. A similar pattern was seen on the afternoon of second proestrus. On the days following first ovulation, serum and ovarian concentrations of 3 alpha-diol were comparable to those during the days preceding this ovulation. The prepubertal decrease in 3 alpha-diol production is discussed in relation to concomitant changes in secretion of estradiol and luteinizing hormone. It is concluded that, in view of the preovulatory resynthesis of considerable amounts of 3 alpha-diol, it is inappropriate to view loss of biosynthetic capacity for 3 alpha-diol as a key event in the onset of puberty. PMID- 4039196 TI - [Changes in the level of eosinophils, corticosterone and catecholamine metabolism in the dynamics of emotional-painful stress]. AB - A correlation has been established between changes in blood eosinophil content, corticosterone level and catecholamine metabolism during emotional painful stress. The authors assume that the differences in the functions of the adrenergic and pituitary-adrenal systems permit an objective determination of the parameters of stress formation in extremal exposures. PMID- 4039197 TI - [Changes in the energy resources of rat gastric mucosa exposed to dopamine agonists and antagonists in conditions of experimental stress]. AB - Changes in adenyl nucleotide and glycogen content in rat gastric tissue under the action of stressogenic factor and injection of the dopamine blocker metoclopramide and the dopamine precursor L-DOPA were investigated with the use of the "social stress" method devised by the authors. It was established that stress induced gastric mucosal lesions and reduced the content of adenyl nucleotides and glycogen in the gastric tissue. Preliminary injection of L-DOPA potentiated the effect of stress while metoclopramide inhibited it. The data show a role of energy balance disturbances in the gastric tissue in the pathogenesis of an acute ulcer. In the authors' opinion, the disturbances seen during immobilization psychogenic stress were caused by undue stimulation of central dopamine receptors. PMID- 4039198 TI - [Catecholamine content of the rat brain at different stages of experimental alcoholism]. AB - Changes in the noradrenaline (NA) content in the hypothalamus, dopamine (DA) and homovanillic acid (HVA) in the striatum were determined in rats after chronic alcohol administration. A single injection of alcohol (2.5 g/kg i.p.) provoked a 30% decrease in NA only in rats predisposed to ethanol intake. Voluntary intake of 15% ethanol for 10 days made the NA content return to normal, the 4-month use of ethanol did not change whereas the 8-month use reduced the NA content by 17%, DA by 31% and raised the content of HVA by 25%. Twenty-four hours after alcohol abstinence the HVA content dropped by 13%. It is concluded that the noradrenergic system is involved in the formation and development of alcohol motivation and that the dopaminergic system participates in the development of the physical dependence and abstinence. PMID- 4039199 TI - [Pharmacoethological analysis of the action of beta-carbolines]. AB - The ethological spectrum of four beta-carbolines was studied for intraspecific aggression, sociability integration and individual behavior. It was established that beta-carboline-3-carboxyethyl ether given at subconvulsant doses increases aggression, lowers sociability as a diazepam antagonist. Diazepam reduces aggression and increases sociability. It is suggested that benzodiazepine receptors are involved in the integration of interspecific sociability and aggressive behavior of the "attack" type. Aggression of the defence type has no inhibitory beta-carboline control (1-methyl-6-methoxy-dihydro-beta-carboline). The differences in the ethological spectra of beta-carbolines have been demonstrated. PMID- 4039200 TI - [Suppression of the formation of cells secreting antibodies and antigen-dependent nonspecific immunoglobulins in mice receiving isologous antierythrocyte immunoglobulins]. AB - Mice injected with syngeneic cellulose-conjugated immunoglobulins (Ig) containing antibodies to sheep red blood cells (SRBC) develop a specific non-responsiveness to SRBC. Such animals demonstrate a sharp decrease not only in the formation of anti-SRBC antibody producers but also of the cells secreting antigen-dependent nonspecific Ig. The inhibition of both these processes is antigen-specific. It is suggested that inhibition of the cells forming antigen-dependent nonspecific Ig is due to suppression of either hypothetic inductors or precursors of these cells expressing an idiotype spectrum similar to that of anti-SRBC antibody producers. PMID- 4039201 TI - [Changes in the opioid peptide content of the adrenals of rats during immobilization stress]. AB - Radioimmunoassay was used to study variation in the content of opioid peptides (leu- and met-enkephalins) in rat adrenal glands at different stages of immobilization stress. The data obtained were correlated to the content of catecholamines (CA). It was discovered that during stress, the content of peptides noticeably increased, being independent of the main pool of CA in adrenal tissue. PMID- 4039202 TI - [Enhanced resistance of the myocardium to stress injury and excess calcium in spontaneously hypertensive rats]. AB - Extensibility, contractile function and resistance to excess calcium of the right atrium myocardium were studied in normotensive Wistar-Kyoto and August rats and in spontaneously hypertensive rats (SHR). It was shown that long-term stress results in a decrease in the measured parameters in normotensive animals. SHR do not show any stress-induced disturbances. It was discovered that in intact SHR rats, the myocardium has a greater resistance to excess calcium, indirect evidence for higher efficiency of the Ca-pump of the sarcoplasmic reticulum in cardiomyocytes of SHR animals, which is apparently a constituent part of the mechanism of such animals' heart increased resistance to stress-induced damage. PMID- 4039204 TI - [Prevention of the depression of normal killer activity in stress via adaptation to the periodic action of hypoxia]. AB - It has been demonstrated that progressive adaptation of BALB/c mice for 28 days to periodic action of pressure chamber hypoxia prevents the stress-induced depression of normal killer activity. Moreover, preadaptation to hypoxia reverses the stress-provoked inhibition of DNA synthesis in the thymic and spleen cells. PMID- 4039203 TI - [Acetylcholinesterase and choline acetyltransferase in the nervous system of rabbits predisposed to cardiovascular disorders under emotional stress]. AB - A study was made of the activity of acetylcholinesterase (AChE), cholinacetyl transferase (CAT), butyril cholinesterase (BCE) and water-soluble proteins in the structures of the CNS and in the autonomous ganglia in rabbits predisposed to cardiovascular disorders under emotional stress. It was established that unlike resistant animals, in those predisposed to cardiovascular disorders, the CAT content in the periphornical area of the hypothalamus did not differ from the control, the content of water-soluble proteins in the CNS structures and the ganglia remained unchanged either as compared with the control. The authors assume that the data obtained confirm a previously advanced concept of the involvement of the cholinergic system of the periphornical area of the hypothalamus in the maintenance of the stability of cardiovascular functions by regulation of the water-salt metabolism. PMID- 4039205 TI - [Changes in the immunity indices of intact and partially hepatectomized mice undergoing the transplantation of splenic cells from hypokinetic donors]. AB - Male (CBA X C57B1/6)F1 mice subjected to a 17-hour movement restrain showed a decrease in splenic and thymic weights and in the number of immunocompetent cells in the blood. Suspension of splenocytes from hypokinetic mice was transplanted to intact and to partly hepatectomized syngeneic animals. One day after transplantation there was a reduction in the weight of the spleen and thymus in intact but not in partly hepatectomized recipients. Seven days after transplantation the number of E-RFC and EAC-RFC dropped in both intact and hepatectomized mice. PMID- 4039206 TI - [Inoperable lung epidermoid cancer non metastasizing. A phase II trial using radiotherapy and combined chemotherapy]. AB - Thirty three evaluable patients with locally advanced squamous cell carcinoma of the lung were entered in a Phase II study combining chemotherapy (Vindesine 1.5 mg/m2 dl; CCNU 50 mg/m2 d2, 25 mg/m2 d3; Cis-Platinum 100 mg/m2 d3; Cyclophosphamide 200 mg/m2 d3, 4, 5) (VCPC) and radical radiotherapy to the primary tumor, mediastinum and supraclavicular nodes. Responders to chemotherapy resumed four additional cycles following radiation therapy. Fourteen patients (42%) presented an objective response to the first two cycles of VCPC. On final evaluation, 18 patients (54.5%) obtained a complete remission and 6 patients (18%) a partial remission. Median survival of all patients was 15.9 months and toxicity was acceptable. We conclude that our results justify a phase III study comparing combined treatment versus radiotherapy alone. PMID- 4039208 TI - Ejaculation and sexual function after endoscopic bladder neck incision. AB - Endoscopic incision of the bladder neck, performed to relieve outflow obstruction, was evaluated as regards effects on ejaculation and orgasm in 61 men (mean age 48 years) by analyses of seminal fluid and a questionnaire. Relief of obstruction was confirmed by post-operative normalisation of urinary flow. In 47 cases there was unchanged antegrade ejaculation, while reduced semen volume was reported by 11 men and retrograde ejaculation by only 3. The quality of orgasm and sexual satisfaction were not permanently changed by the operation. Post operative analysis of seminal fluid was performed in 27 patients, with normal results in 26. In 16 men who provided specimens both before and after bladder neck incision, no consistent change was found in the semen. An incision completely splitting the bladder neck but not extending distal to the verumontanum will relieve outlet obstruction. Maintenance of antegrade ejaculation can be expected in most patients undergoing this operation. PMID- 4039207 TI - [Changes in mean erythrocyte volume during cisplatin treatment]. PMID- 4039209 TI - Thrombotic thrombocytopenic purpura presenting as an acute abdomen. PMID- 4039210 TI - Unidirectional non-cross-tolerance (UNCT) in rats and an apparent dissociation between narcotic tolerance and physical dependence. AB - The phenomenon of unidirectional non-cross tolerance (UNCT) to etorphine was observed in adult male rats tolerant to morphine. Using a morphine pellet (four 75 mg morphine pellets) implantation protocol, a 10-fold increase in the analgesic ED50 value, obtained by tail-flick assay, was observed for morphine sulfate, with no alteration in analgesic ED50 value for etorphine. After etorphine pellet (two 60 micrograms pellets) implantation, no significant change in the ED50 value for etorphine was observed, but the ED50 value for morphine increased 15-fold. Both morphine and etorphine pellet-implanted animals, challenged with naloxone, showed similar qualitative signs of precipitated withdrawal. This seeming dissociation obtained by demonstration of physical dependence in the absence of tolerance to etorphine has its basis in the UNCT phenomenon. Thus, appropriate experimental paradigms must be included when evaluating tolerance to avoid specious conclusions. PMID- 4039211 TI - Responses of thalamic and hypothalamic neurons to scrotal warming in rats: non specific responses? AB - Activities of thalamic and hypothalamic neurons in response to scrotal temperature change were investigated in urethanized (1.2-1.5 g/kg) rats with special attention to changes in cortical electroencephalogram (EEG). Somatosensory relay neurons were identified electrophysiologically in the ventrobasal complex (VB) of the thalamus. These neurons had tactile receptive fields in areas outside the scrotum. Forty out of 44 of these neurons responded to scrotal warming by increase in firing rate. The responses occurred abruptly at threshold temperatures ranging from 31 to 40 degrees C (switching response) with simultaneous changes in EEG from high to low voltages (desynchronization). In both the thalamus and the hypothalamus, neurons excited or inhibited by scrotal warming were also excited or inhibited, respectively, by noxious stimulation that produced EEG desynchronization. Neurons showing no response to scrotal warming were not affected by noxious stimulation. In deeply anesthetized (2.5 g/kg urethane) rats, VB relay neurons responded to tactile stimulation of their receptive fields, but scrotal warming produced no change in either EEG or activities of thalamic and hypothalamic neurons. These facts suggest that the responses of thalamic and hypothalamic neurons to scrotal warming may be 'non specific'. Most thalamic and hypothalamic neurons showing switching responses did not appear to mediate specific information concerning scrotal skin temperature. PMID- 4039212 TI - Spatial distribution of dopamine, methotrexate and antipyrine during continuous intracerebral microperfusion. AB - The spatial distributions of 3 model drugs, [14C]dopamine hydrochloride (DA), [3H]sodium methotrexate (MTX) and [14C]antipyrine (AP), were determined after 6 days continuous microperfusion of the diencephalon of rabbits. The basic pattern of distribution was the same for each drug: the tissue concentration, expressed as a function of the perfusate concentration, was maximal at the cannula tip, and declined sharply with radial distance from the tip. However, at any given distance, concentrations of radioisotopes derived from DA and MTX, both ionized, lipid-insoluble drugs, were one to two orders of magnitude higher than those derived from AP, a lipid-soluble drug. Although concentrations of isotopes derived from DA and MTX were in the same range, their distribution patterns were consistently different. The results demonstrate that intracerebrally microperfused drugs may have quantitatively different spatial distributions, related to their physicochemical characteristics and/or their binding and metabolism in brain tissue. PMID- 4039213 TI - The organization of the hypothalamic pathways mediating affective defense behavior in the cat. AB - The purpose of this study was to describe the hypothalamic pathways which mediate affective defense in the cat utilizing the methods of [14C]2-deoxyglucose (2-DG) and [3H]leucine radioautography in concert with the technique of electrical brain stimulation. The feline affective defense response, characterized by pupillary dilatation, piloerection, ear retraction, hissing, growling and striking with the forepaws, was elicited consistently by stimulation of sites within the ventromedial hypothalamus and anterior aspect of the medial hypothalamus. In one series of experiments, 2-DG autoradiography was employed to describe the brain regions activated following stimulation of sites in the region of the ventromedial hypothalamus from which affective defense had been elicited. Ventromedial hypothalamic stimulation produced activation primarily in forebrain regions situated rostral to the level of the stimulating electrode. These structures included principally the anteromedial hypothalamus and medial preoptic area, as well as the bed nuclei of the stria terminalis and anterior commissure, diagonal band and lateral septal area. The caudal extent of activation included only the dorsal and perifornical hypothalamus at the level of the stimulation site. In a second series of experiments, affective defense sites in the anteromedial hypothalamus were stimulated and the regional distribution of 2-DG label was identified. In contrast to the results obtained from ventromedial hypothalamic stimulation, these experiments revealed a marked descending distribution of label within the posterior hypothalamus, midbrain central gray and ventral tegmental area. Results obtained from studies in which tritiated amino acids were injected into affective defense sites in both the ventromedial nucleus and anteromedial hypothalamus confirmed the general findings observed with 2-DG autoradiography. From these observations, we have concluded that the organization of the pathway mediating affective defense behavior from the ventromedial hypothalamus to the midbrain involves an initial synapse within the region of the anteromedial hypothalamus and a second synapse in the midbrain central gray substance. The significance of the anteromedial hypothalamus for the expression of affective defense behavior was considered in the Discussion. PMID- 4039214 TI - The role of the anterior hypothalamus in affective defense behavior elicited from the ventromedial hypothalamus of the cat. AB - In the preceding paper a hypothalamic circuit subserving feline affective defense behavior was described. This circuit included an ascending component from the ventromedial nucleus to the anterior hypothalamus and a descending component from the anterior hypothalamus to the midbrain central gray substance. The present study was undertaken to test the hypothesis that the anterior hypothalamus plays a central role in the organization of this functional pathway. In the first part of this study, dual stimulation methods were utilized to demonstrate that concurrent stimulation of the ventromedial hypothalamus facilitates the occurrence of affective defense responses elicited from the anterior hypothalamus. In the second part of the study, lesions placed in the anterior hypothalamus significantly increased the latency and threshold current for affective defense responses elicited from the ventromedial hypothalamus. [14C]2 deoxyglucose autoradiography confirmed the fact that anterior hypothalamic lesions effective in blocking affective defense were placed in regions where the vast majority of ventromedial hypothalamic fibers terminate. In contrast, lesions which had little or no effect upon the latency or threshold for affective defense elicited from the ventromedial hypothalamus appeared to leave intact the connections from the ventromedial to the anterior hypothalamus. These findings are consistent with the proposed intrahypothalamic anatomical substrate subserving affective defense behavior described in the preceding paper. PMID- 4039215 TI - Enhancement of some 5-HT-dependent behavioural responses following repeated immobilization in rats. AB - Responses to drugs affecting 5-hydroxytryptamine (5-HT) and dopaminergic (DA) system have been examined in rats after repeated immobilization. Groups of rats were immobilized for 2 h per day for up to 7 days. Twenty-four hours later their behavioural responses to various drugs were tested. Rats immobilized for 7 days showed decreased sniffing and increased grooming and body shakes. When given amphetamine (3 mg/kg, i.p.) the intensity of classical dopamine-dependent behaviours was similar to that of non-immobilized controls. Some responses to the 5-HT releaser p-chloroamphetamine (PCA) (4 and 10 mg/kg, i.p.) and the 5-HT agonist 5-methoxy-N,N-dimethyltryptamine (5-MEODMT) (5 mg/kg, i.p.) (forepaw treading and tremor) were enhanced after 7 days immobilization but others (limb abduction and headweaving) were not. These responses were not enhanced after 1 or 3 days immobilization. Backward walking and body shakes induced by PCA were also enhanced after 7 days immobilization. Concentrations of 5-HT, DA and their metabolites in striatum, cortex, hippocampus, hypothalamus and midbrain of non drug-treated control and immobilized groups were comparable. Brain PCA concentrations 30 min after injection were also comparable. The above biochemical and behavioural data suggest that repeated immobilization increases some 5-HT postsynaptic functions. These results are discussed in relation to non-drug provoked behavioural abnormalities occurring 24 h after the first immobilization but no longer evident after 7 periods of immobilization. PMID- 4039216 TI - Heterogeneity of peptides released by electrically active neuroendocrine caudodorsal cells of Lymnaea stagnalis. AB - The peptidergic caudodorsal cells (CDC) are located in the cerebral ganglia (CG) of the snail Lymnaea stagnalis. They have the periphery of the intercerebral commissure (COM) as the neurohaemal area. Release of the ovulation hormone (CDCH) and other presumed peptides by electrically active CDC was studied in vitro using CG/COM preparations which were preincubated with radioactive amino acids. Electrical activity of the CDC was induced by electrical stimulation of these cells, and by adenosine 3',5'-cyclic phosphate (cAMP) or potassium depolarization. Four classes of radioactively-labelled peptides are released by active CDC. They have molecular weights of greater than or equal to 6000, approximately 5500, approximately 4500 and approximately 2500 daltons, respectively. Released CDCH bioactivity co-eluted with the approximately 4500 dalton radioactive peptides. Selective removal of CDC demonstrated that the CDC release these peptides. cAMP and potassium depolarization also induce release of these peptides. The release after potassium depolarization is dependent upon the presence of calcium ions. CG/COMs from juvenile snails are not capable of releasing the peptides. With Bio-Gel P-6 chromatography, sodium dodecyl sulphate urea polyacrylamide electrophoresis, isoelectric focusing and proteolytic enzymes it was found that released CDCH is a peptide with the same molecular weight and pI as CDCH stored in the COM (molecular weight approximately 4700; pI approximately 9.3). PMID- 4039217 TI - Kindling in the amygdala and susceptibility to stress ulcers. AB - Kindling in the centromedial amygdala facilitated the subsequent development of restraint-induced stomach ulcers in rats. It was suggested that the neuronal hyperexcitability produced by the kindling procedure led to an increased susceptibility to gastric pathology in response to stress. PMID- 4039218 TI - Effects of amino and ammonio derivatives of adenosine on smooth muscle preparations and mouse neuroblastoma adenylate cyclase. AB - Several amino- and ammonio-substituted derivatives of adenosine were tested as effectors of adenosine receptors in different smooth muscle preparations and mouse neuroblastoma adenylate cyclase. The compounds did not affect adenosine receptors in smooth muscles. N6-[3-(trimethylammonio)propyl]adenosine was a weak stimulator of adenylate cyclase, and 3'-amino-3'-deoxyadenosine and 3' monomethylamino-3'-deoxyadenosine antagonized the stimulation of adenylate cyclase by 2-chloroadenosine. PMID- 4039219 TI - Extraction of a murine tumor-specific antigen from cells and plasma membranes using 1-butanol: augmentation of antigen yield by colchicine. AB - The purpose of this investigation was to examine the ability of single-phase aqueous solutions of 1-butanol to release immunoprotective tumor antigen activity from partially purified plasma membranes of the methylcholanthrene-induced fibrosarcoma, MCA-F. Tumor antigen activity was assessed by s.c. immunization of syngeneic C3H/HeJ mice 10 days prior to supralethal challenge. Although brief incubation of intact MCA-F cells in 2.5% butanol releases potent immunoprotective activity, application of this protocol to plasma membranes did not result in antigen extraction. Modification of the extraction protocol using higher concentrations of butanol and longer extraction times did release measurable tumor antigen activity. However, a significant amount of the membrane-associated activity remained with the insoluble membrane fraction, as demonstrated by the immunoprotective capacity of the extracted membranes. The dramatic difference in the extractability of antigen from intact cells and plasma membranes suggested that membrane architecture may influence antigen release. To investigate this possibility, we extracted with butanol MCA-F cells that had been preincubated in colchicine. Treatment of cells with colchicine significantly potentiated the extraction of tumor antigen activity. Augmentation of antigen yield was also observed when plasma membranes were pretreated with colchicine prior to 2.5% butanol extraction. These results suggest that the tumor-specific transplantation antigen may be directly or indirectly associated with the cytoskeleton underlying the plasma membrane. PMID- 4039220 TI - Prediction of in vivo tumor response to chemotherapeutic agents by the in vitro sister chromatid exchange assay. AB - The ability of the in vitro sister chromatid exchange (SCE) assay to predict in vivo tumor drug sensitivity was investigated using a spontaneous hepatocarcinoma in C3Hf/Kam mice and 3 chemotherapeutic agents: melphalan; cis-platinum; and 1,3 bis(2-chloroethyl)-1-nitrosourea (BCNU). For hepatocarcinoma cells grown in monolayer culture, melphalan was the most efficient at inducing SCEs, and BCNU, the least. cis-Platinum induced a range in SCEs that overlapped those of BCNU and melphalan, suggesting that hepatocarcinoma is not a homogeneous population with intermediate sensitivity, but is a mixture of cis-platinum-sensitive and resistant cells. According to in vitro cell survival curves, hepatocarcinoma was most sensitive to melphalan, less sensitive to cis-platinum, and essentially resistant to BCNU. The relative antineoplastic effects of melphalan, cis platinum, and BCNU in vivo were compared by the response of artificial and spontaneous pulmonary metastases and solid tumors to these agents. For artificial metastases, there was a dose-dependent decrease in the number of lung nodules in mice treated with melphalan or cis-platinum, with melphalan being the more effective. BCNU had no effect. Spontaneous pulmonary metastases generated from hepatocarcinoma leg tumors were reduced in those mice treated with melphalan, unaffected by cis-platinum, and increased by BCNU. In hepatocarcinoma leg tumors (5 to 6 mm in diameter), melphalan induced the longest growth delay, and BCNU the least. Therefore, the relative effects produced by these three drugs in vivo were the same as predicted by SCE induction in vitro. The SCE assay may thus have potential clinical application. PMID- 4039221 TI - Differential response of cultured human normal and tumor cells to trace element induced resistance to the alkylating agent melphalan. AB - Previous studies using cultured Chinese hamster cells indicated that pretreatment of the cells with the trace elements copper, selenium, and/or zinc resulted in increased survival of the metal-induced cultures following subsequent exposure to mono- and bifunctional alkylating agents. To ascertain whether a comparable protective response could be activated in human-derived material, a series of human normal and tumor cells was treated with these trace elements and later challenged with the alkylating agent melphalan, prior to determination of the surviving fraction via colony formation. Normal human cells derived from either newborn infants or adults exhibited an increase in survival of 7- to 9-fold when pretreated with zinc alone that increased to approximately 16-fold when these normal cells were induced with all three trace elements. In contrast, comparable pretreatment of tumor cell populations resulted in an increase in survival of 1.7 fold or less, with most types of tumors exhibiting no induced protection. These observations describing a differential inducibility of normal and tumor cells raise the possibility of a novel approach for selectively sparing normal tissue in patients undergoing treatment with alkylating agents. Possible ramifications to cancer chemotherapy are discussed. PMID- 4039222 TI - Relationship between the organization and synthesis of vimentin and the metastatic capability of B16 melanoma cells. AB - The organization and synthesis of the vimentin-containing cytoskeletal network as well as the metastatic capability of B16-F1 melanoma cells were investigated in cells treated with cycloheximide (CH). The addition of CH to cells for 4-8 h resulted in a marked reversible alteration in the organization of the vimentin containing network in B16-F1 melanoma cells as well as in a variety of epithelial and fibroblast cell lines. Treatment of cells with CH led to a reduction in the synthesis of vimentin, tubulin, and actin followed by a decrease in the concentrations of mRNAs coding for these proteins. However, out of these three cytoskeletal elements, only the organization of the intermediate filaments was disrupted by CH. Cells treated previously with CH and injected i.v. into syngeneic mice had diminished capacity to form lung metastases as compared to control untreated cells. This effect was reversible, and the metastatic capability recovered to the control level after the drug was removed from the growth medium for 16 h. The possibility that the organization and the synthesis of the cytoskeletal components are related and that the metastatic capability of B16 melanoma is influenced by the organization of the cytoskeletal networks are discussed. PMID- 4039223 TI - Reactive oxygen dependent activation of polycyclic hydrocarbons by phorbol ester stimulated human polymorphonuclear leukocytes. PMID- 4039224 TI - Quasi-exponential generation time distributions from a limit cycle oscillator. AB - In spite of the apparently random behaviour and the often exponential distribution of generation times expressed in cell populations, there is evidence for rather precise timekeeping in the cell cycle. In experiments using time-lapse video-tape microscopy, we have noted that cell generation times are often not distributed smoothly but in many cases seem to cluster at roughly 4 hr intervals. Phase shift responses following application of heat shock, ionizing radiation or serum pulses in each case show a pattern which is repeated twice in cells with an 8-9 hr modal generation time. We describe here a cell cycle model with an independent cellular clock controlling cell cycle events which accounts for the phase response data, while also reconciling the stochastic and periodic behaviour characteristic of animal cells. PMID- 4039225 TI - The influence of the route of antigen administration on the development of specific antibody-producing cells in the follicles of the popliteal lymph nodes of rabbits. AB - Rabbits received an injection of liposome-associated human serum albumin (HSA) and six weeks later a booster injection of HSA free in solution. Anti-HSA antibody-forming cells were demonstrated in the popliteal lymph nodes by use of a HSA-horseradish peroxidase (HRP) conjugate for their detection. After a single subcutaneous injection into the footpads, specific antibody-forming cells were found, but after a single intravenous injection no anti-HSA-forming cells were observed in the lymph nodes. During the secondary immune response specific anti HSA antibody-producing cells were found in the lymph nodes of all animals. The localization pattern of anti-HSA antibody-forming cells within the lymph nodes depended on the route of antigen administration used for the primary and booster injection. Anti-HSA-forming cells were mainly found in the cords of the medulla and in the outer cortex. During the secondary immune response, however, they were also detected in the follicles but only when at least one of the two antigen injections was given subcutaneously. PMID- 4039226 TI - Cost and utilization of the new cardiac imaging modalities. PMID- 4039227 TI - The quantitative detection of various Pt-DNA-adducts in Chinese hamster ovary cells treated with cisplatin: application of immunochemical techniques. AB - With polyclonal antibodies raised against cis-Pt(NH3)2Guo-GMP, small quantities of specific Pt-adducts could be detected in DNA from Chinese hamster ovary (CHO) cells treated with the antitumor agent cisplatin, after the DNA had been digested with nucleases and the degradation products separated by anion-exchange chromatography (FPLC). Directly after treatment with 83 microM cisplatin, resulting in 97 X 10(-6) platinum atoms bound per nucleotide, 35.9 +/- 4.7% of the platinum was recovered as cis-Pt(NH3)2d(pGpG), derived from intrastrand cross links on two neighboring guanines, 3.1 +/- 1.6% as cis-Pt(NH3)2d(GMP)2, the degradation product of interstrand cross-links on two guanines (0.07%, according to separate studies) and of intrastrand cross-links on two guanines separated by one or more bases. The immunochemical method was not sensitive enough for the detection of monofunctionally bound platinum on guanine residues. The amount of these adducts, present in the digests as Pt(NH3)3dGMP, could be established with atomic absorption spectroscopy (AAS) (38.5% of the total Pt-content of the DNA). After a post-treatment incubation of the cells for 24 h, the total amount of platinum decreased to 59 X 10(-6) atoms per nucleotide, indicating the removal of adducts. In the digests, cis-Pt(NH3)2d(pGpG) accounted for 46.4 +/- 6.8% of the total Pt-content, cis-Pt(NH3)2d(GMP)2 for 3.0 +/- 0.9% (0.34% derived from DNA interstrand cross-links). The amounts of monofunctional adducts had decreased to such an extent that the exact quantities (below 15%) could not be determined. According to AAS-assays, at the elution position of cis-Pt(NH3)2d(pApG) a significant amount of Pt-product was present, both at t = 0 and 24 h, but the signals did not allow quantitative evaluation (however, below 48% and 28%, respectively). The possible role of the individual lesions in the DNA in the biological effects of this platinum compound in CHO cells is discussed. PMID- 4039228 TI - Covalent binding of diethylstilbestrol to microsomal protein in vitro correlates with the organotropism of its carcinogenicity. AB - [14C]Diethylstilbestrol (DES) was incubated in vitro with liver and kidney microsomes from male and female hamsters and rats, and the extent of non extractable binding of radioactivity to microsomal protein was determined. Binding to microsomes from male hamster kidney, which is a target organ for DES carcinogenicity in vivo, was found to be 5-10 times higher than binding to microsomes from non-target tissues. Pretreatment with phenobarbital led to a marked increase in binding of DES to kidney microsomes but not to liver microsomes from female hamsters and male and female rats. The correlations of in vitro covalent binding with organ susceptibility implies a role for metabolic activation of DES in the mechanism of its carcinogenicity. PMID- 4039229 TI - Studies on vitamin D binding protein in the nephrotic syndrome. AB - We studied the properties of vitamin D binding protein in plasma and urine from nine patients with nephrotic syndrome. Samples were incubated with 25 [3H]hydroxyvitamin D3, after which we determined binding capacity and apparent dissociation constants. Binding capacity was markedly less in plasma from patients with nephrotic syndrome than that from normal subjects, but binding affinity was unchanged. Specific binding of 25-hydroxy[3H]vitamin D3 could be demonstrated in urine from all the nephrotic patients, and sucrose density gradient analysis of these urines revealed a single binding peak with sedimentation characteristics similar to those of vitamin D binding protein in plasma. PMID- 4039230 TI - Diabetes in pregnancy. An epidemiologic study by Department of Obstetrics and Gynaecology of Sassari University from 1974 to 1983. AB - We examined 102 pregnancies in 59 diabetic women by Department of Gynaecology and Obstetrics of Sassari University from 1974 to 1983, we evaluated pregnancy and labor proceeding, perinative morbidity and mortality. Our issues show a perinative mortality high yet (14.8%), not always comparable to severity of maternal diabetes, that's mainly due to insufficient number of controls undertaken from patients for their por medical education. Recently diabetic pregnant women have getting used to routine controls of metabolic balance, pregnancy evolution and fetal well-being through biochemical and biophysic monitoring; that allows to obtain an improvement of perinative mortality. PMID- 4039231 TI - Comparison of DHT-binding and monoclonal immunoradiometric methods for the measurement of sex hormone-binding globulin. PMID- 4039232 TI - A new ELISA method for the detection of serum bindable anti-platelet antibodies (SPBIG). PMID- 4039233 TI - Parathyroid hormone-like bioactivity in a patient with severe osteitis fibrosa cystica due to malignancy: renotropic actions of a tumour extract as assessed by cytochemical bioassay. AB - A patient is described with malignancy, hypercalcaemia and radiological evidence of severe parathyroid bone disease but undetectable concentrations of circulating immunoreactive PTH. Autopsy showed the tumour to be a metastatic bronchial carcinoid with no evidence of primary parathyroid disease. Extracts of the tumour had no PTH immunoreactivity but had high concentrations of a substance with identical activity to PTH in a cytochemical bioassay. The biological activity of the extract was not inhibited by PTH antibodies but was inhibited by an antagonist to PTH bioactivity. PMID- 4039235 TI - Paternal mosaic 45,X/46,XYq+ and recurrent spontaneous abortions without monosomy X. PMID- 4039234 TI - Bromocriptine therapy in acromegaly: effects on plasma GH levels, somatomedin-C levels and clinical activity. AB - Thirty-one patients with active acromegaly were treated with 10-20 mg bromocriptine daily for a period of 6-9 months. The clinical response was evaluated both by a subjective 'score of symptoms', and by a combined subjective and objective 'clinical and metabolic improvement score' (c-m score). The biochemical response was evaluated both by measurement of the mean of four plasma growth hormone (GH) determinations during the day and by measurement of plasma somatomedin-C (Sm-C) concentration. The clinical response as assessed by both methods showed a better correlation with changes in plasma GH levels (respectively r = 0.33; r = 0.50) than with changes in Sm-C levels (r = 0.20; r = 0.36). The study confirms that in some patients clinical improvement is not accompanied by a decrease of plasma GH concentration. However, it is not possible to identify a subgroup of patients who showed clinical improvement with a decrease of Sm-C levels, but whose plasma GH levels remained constant. It is concluded that measurement of plasma GH levels still appears to be the most useful biochemical assessment of disease activity in bromocriptine-treated acromegaly. PMID- 4039236 TI - Skin disease in homosexual patients with acquired immune deficiency syndrome (AIDS) and lesser forms of human T cell leukaemia virus (HTLV III) disease. PMID- 4039237 TI - Thrombotic thrombocytopenic purpura and hemolytic uremic syndrome in pregnancy. PMID- 4039238 TI - Hemangioblastoma of the cauda equina. AB - A very rare hemangioblastoma of the filum terminale with sciatic pain and partial cauda syndrome in a 36-year-old man is presented. The difference between solitary hemangioblastoma, hemangioblastomatosis and von Hippel-Lindau disease is stressed. The literature is reviewed and the diagnosis of cauda equina neoplasms is discussed. Even nowadays often the final diagnosis is made late and only after operation and microscopical tissue examination. PMID- 4039239 TI - Quantitative analysis of liver function in percutaneous transhepatic biliary drainage patients. AB - The diagnostic usefulness of Tc-99m DISIDA cholescintigraphy as a predictor of eventual catheter and hepatic function in patients who have undergone percutaneous transhepatic biliary drainage (PTBD) for extrahepatic biliary obstruction was evaluated. Twenty-nine cholescintigrams were performed in 14 patients. The examinations were divided into two groups: Group A (N = 17), in which the patient's clinical status deteriorated within two to three days post PTBD, and Group B (N = 12), in which the patients did well clinically post-PTBD. No significant difference between the two groups was demonstrated by visual analysis of the analog images or by analysis of serum bilirubin levels. A computer program, developed by the authors, quantitates several parameters of DISIDA kinetics, reflecting hepatic function based upon compartmental analysis. A significant difference (P less than .001) was demonstrated between the mean transport constants (blood clearance constant = k1; hepatic clearance constant = k2) for the two groups. It is concluded that serum bilirubin levels and visual inspection of analog images are inadequate independent predictors of hepatic function in patients post PTBD. The transport constants k1 and k2 are quantitative parameters of hepatic function that may be of prognostic value in patients post PTBD. PMID- 4039240 TI - Hepatobiliary-lung imaging. A case report. AB - The use of combined hepatobiliary-lung imaging in the diagnosis and evaluation of a subphrenic process is described. PMID- 4039241 TI - Grand rounds. Immune globulin in the treatment of autoimmune thrombocytopenic purpura. AB - Two patients with autoimmune thrombocytopenic purpura (ATP) who received high dose intravenous immune globulin before undergoing splenectomy are described, and the pathogenesis, clinical presentation, diagnosis, and treatment of chronic ATP are reviewed. One patient was a 62-year-old white man who was admitted to the hospital with a history of thrombocytopenia and probable steroid-induced diabetes mellitus. The second patient was a 24-year-old black woman who was admitted for recurrent bleeding episodes and splenectomy. In both patients, immune globulin 1.5 g/kg administered over four to six days resulted in marked elevations of platelet counts. ATP is a platelet disorder of unknown etiology. Platelets with surface-bound antiplatelet antibody are destroyed by the reticuloendothelial system. As the platelet count falls below 30,000-50,000/cu mm, the patient may manifest signs of bleeding such as petechiae, purpura, ecchymosis, menorrhagia, epistaxis, and bleeding from other mucosal surfaces. Corticosteroids are the initial treatment of choice. Splenectomy is considered for children with the life threatening hemorrhage and for patients who do not respond to corticosteroids. Patients who are refractory to steroid therapy and splenectomy may respond to immunosuppressant agents. Approximately, 80% of patients treated with immune globulin have responded with an increase in platelet count, although this increase is sometimes transient. Immune globulin therapy is recommended for emergency treatment of ATP, as preoperative medication before splenectomy, and for young children in order to postpone splenectomy. Despite a good response to treatment, immune globulin therapy should not be considered a cure for ATP. PMID- 4039242 TI - CT measurements of the anterior portions of the diaphragm with illustrative abnormal cases. AB - One hundred and two adult patients without evidence of diaphragmatic disease were examined by computed tomography. Patients were excluded who had evidence of neoplasma frequently associated with peritoneal implants, liver metastases, ascites, or pleural effusions. The anterior portion of the right diaphragm leaflet could be evaluated in thirteen patients and the left in 82. The normal range of diaphragm thickness was 1.2-28.6 mm on the left and 2.6-26 mm on the right. Causes for apparent increased thickness of the diaphragm leaflets are discussed and several abnormal cases illustrated. PMID- 4039243 TI - Forskolin suppresses sympathetic neuron function and causes ocular hypotension. AB - Recent reports suggest that forskolin can produce ocular hypotension in laboratory animals and man by enhancing formation of cyclic AMP. This proposed mechanism of action implies that forskolin lowers intraocular pressure (IOP) by activating adenylate cyclase at some postjunctional site. Intra-arterial (i.a.) injections of forskolin (10, 33, 100 & 333 micrograms) into the cat nictitating membrane (CNM) preparation produced dose-related inhibition of contractions elicited by electrical stimulation of pre-and postganglionic sympathetic neurons. Interestingly, contractions elicited by i.a. norepinephrine were inhibited less than neuronally mediated contractions. Topically applied forskolin (0.5 mg) to the eyes of unilaterally sympathectomized (SX) rabbits and normal rabbits elicited ocular hypotension in the innervated eyes only. Forskolin (0.5 mg, topically) suppressed the rise in IOP induced by water loading in normal rabbits but was significantly less effective in SX rabbits. These results suggest that forskolin lowered IOP in rabbits and suppressed contraction of the electrically stimulated CNM, in part, by inhibiting sympathetic neuronal function. PMID- 4039244 TI - The structural development of Alzheimer's disease. PMID- 4039245 TI - The relation between neonatal and later activity and temperament. AB - Evidence from several longitudinal studies suggests that individual activity characteristics tend to persist over time and to influence the development of temperamental style. The activity of 50 children whose motility had been monitored by an electronic activity monitor when they were neonates was again monitored by an ambulatory microcomputer when they were 4-8 years old. Additionally, the parents of these children filled out the Behavioral Style Questionnaire by McDevitt and Carey. The results showed that the level of the children's day and night activity was unrelated. The vigor of neonatal movements was later positively related to high daytime activity. Also, the least vigorous infants tended to become the most inactive children during the day. The results further showed that the most active neonates became children who, as perceived by their parents, tended to approach rather than withdraw from new experiences. PMID- 4039246 TI - Centromere ultrastructure in germ-line chromosomes of Parascaris. AB - Ultrastructural analysis of the centromere in germ-line mitotic chromosomes of Parascaris univalens and Parascaris equorum revealed that these chromosomes are holocentric. In thin longitudinal sections of both species the kinetochore appeared as a continuous plate (up to 3.8 micron long) and displayed a layered structure. This structure consisted of electron-dense inner and outer layers (average width 10 nm) separated by a less dense middle layer (25 nm wide), which had transverse electron-dense bars (10 nm wide) regularly spaced every 25-30 nm. Thus the ladderlike kinetochore profile observed in Parascaris gonial mitotic chromosomes represents a different type of organization from that of the classical trilaminar kinetochore found in both holocentric and monocentric chromosomes. PMID- 4039247 TI - [Dexterous digital movements of the non-preferred hand--a test of 46 normal subjects]. PMID- 4039248 TI - Estrogen responsiveness of normal mouse mammary cells in primary cell culture: association of mammary fibroblasts with estrogenic regulation of progesterone receptors. AB - Estrogens enhance proliferation of normal mouse mammary cells in vivo. However, when cultured alone, normal mouse mammary epithelial cells fail to exhibit a proliferative response to estrogen in vitro; the basis for this lack of in vitro responsiveness to estrogen is not known. The purpose of the present study is to determine if cultured normal mouse mammary cells possess estrogen receptors (ER) and/or progesterone receptors (PgR) and if the ER mechanism is functional, as measured by the ability of estrogens to regulate PgR. Recent findings that mammary fibroblasts can influence the behavior of mammary epithelial cells in vitro led us to investigate their effect on epithelial cell responsiveness to estrogen. In these studies, collagenase-dissociated mammary glands of midpregnant BALB/c mice were the source of mixed cultures (containing both epithelial cells and fibroblasts) and epithelial or fibroblast cultures. The purity of epithelial or fibroblast cultures was quantified immunocytochemically using antivimentin antibody as a fibroblast marker. Steroid hormone binding was quantified in intact cultured cells using [3H]R5020 and 17 beta-[3H]estradiol as the ligands. Specific high affinity binding sites for estrogen (Kd = 3.1 +/- 0.8 X 10(-10] and progestins (Kd = 3.3 +/- 1.2 X 10(-9) M) were detected in mixed cultures. To assess the possible role of mammary fibroblasts, we investigated cultures containing only fibroblasts which were derived by differential centrifugation. When 17 beta-estradiol was added to the culture medium, a significant (P less than 0.01) increase in PgR concentration was observed in mixed cultures. While mixed cultures maintain responsiveness to estrogen in vitro, as measured herein, the epithelial cultures, derived by differential centrifugation and Percoll gradient sedimentation, did not. However, estrogenic regulation of PgR appears to be specific to epithelial cells in mixed cultures, since fibroblast cultures neither contained PgR nor displayed estrogen-inducible PgR. The lack of responsiveness of epithelial cultures is not due to a loss or decrease in the ER concentration. Thus, the presence of mammary fibroblasts appears to be associated with epithelial cell responsiveness to estrogen in vitro. PMID- 4039249 TI - Alternate photoperiods time puberty in the female lamb. AB - In the spring-born lamb, puberty, the onset of repetitive ovarian cycles, occurs between 25 and 35 weeks of age during the decreasing day length of autumn. This study was conducted to determine the photoperiod conditions required for puberty. Several artificial photoperiod treatments were used, beginning from birth or soon after. Continuous exposure to long days or to short days delayed the first normal luteal cycle beyond 1 yr of age. Similarly, a single block of 4 or 10 weeks of long days at early ages, from either 3-7 or 3-13 weeks of age (afterwards under short days), produced only a few consecutive cycles within the first year after birth. However, exposure to blocks of long days at later ages resulted in the onset of cycles during the normal pubertal period. Lambs that experienced a 10 week block of long days (12-22 weeks of age; otherwise under short days) began reproductive cycles at 34 weeks of age. Reduction of the single block of long days to 5 weeks (17-22 weeks of age) or 1 week (week 22 of age) also resulted in the onset of normal luteal cycles within the normal age range for puberty. The results indicate that a sequence of long days followed by short days is required to initiate and sustain ovulatory cycles at the normal age in the lamb. Moreover, the age when long days are experienced is important, with later exposure to long days being more effective in producing consecutive cycles than early exposure to long days. These findings raise the possibility that the spring-born lamb uses a portion of the long days of summer to time the onset of puberty during the short day lengths of autumn. PMID- 4039250 TI - Combined therapy of malignant stenoses of the upper gastrointestinal tract by means of laser beam and bougienage. AB - Eighteen patients with malignant inoperable stenoses of the upper digestive tract were treated with a combination of laser (neodymium-YAG) coagulation and bougienage. Following treatment, 14 out of 18 patients (78%) were able to eat solid food again; the width of the lumen was greater than 11 mm in every case. Between 1 and 5 laser sessions (median 3.5) and between 1 and 2 (median 1) bougienages were required; per session, between 1,017 and 9,096 joules (median 3,362) were required, and a total of between 4,770 and 36,244 joules (median 8,763) were utilized per patient treated. To date, 6 patients remain free of dysphagia (at between 3 and 24 weeks), 1 patient has in the meantime been submitted to surgery. In 7 patients, recurrent stenosis occurred, which was again treated with the laser (3) or with an endoscopically implanted prosthetic tube (4). In 4 patients, the result was unsatisfactory. By way of major complications, merely one perforation occurred. We conclude that the combined use of laser coagulation and bougienage represents an effective and largely complication-free palliative treatment for malignant stenoses in the upper digestive tract. PMID- 4039251 TI - Side effects of endobronchial laser treatment. AB - Side effects that have occurred in over 250 endobronchial laser treatments are reported. The laser has been used in severe tracheal and in bronchial obstructions. In two cases significant bleeding had to be treated with tamponade. In one patient an emphysema of the mediastinum developed, in 2 further patients a small pneumothorax. Perforation of the airway was not detected and no special treatment was necessary. Three patients with life-threatening tracheal stenoses and one patient with severe stenosis of both the mainstem bronchi due to metastasis in the bifurcation lymph node had a large defect in the tracheal or bronchial wall with a deep necrosis five to twelve weeks after laser treatment; all these patients had extensive radiotherapy in addition. One patient died due to severe respiratory insufficiency, probably caused by smoke intoxication. After the laser treatment, rubber-like fibrin-rich plaques may develop, which can lead to life-threatening obstructions of the airway. It is recommended that laser bronchoscopy should be performed with the rigid bronchoscope. After treatment of tracheal lesion an endoscopic check must be performed within 24 hours. The combination of laser treatment and radiotherapy seems to involve a certain risk of large defects in the bronchial wall due to necrosis of the tumour. PMID- 4039252 TI - Time resolved fluorescence of bacteriophage Pfl DNA binding protein and its complex with DNA. AB - The DNA binding protein of the filamentous bacteriophage Pfl exhibits fluorescence from a single tryptophan residue. The location of the emission maximum at 340 nm ist quite common for proteins, but the single lifetime of 7.8 ns is one of the longest yet reported. Protein fluorescence is quenched more efficiently by Cs+ than by I-; the Trp is located in a partially exposed pocket, in the vicinity of a negative charge. In the native complex of the binding protein with Pfl DNA the fluorescence emission maximum is at 330 nm, indicating a more apolar environment for Trp 14. The native nucleoprotein complex exhibits a similar fluorescence lifetime (6.5 ns) and an approximately equal fluorescence yield, indicating the absence of Trp-DNA stacking. The tryptophan in the complex is virtually inaccessible to ionic quenchers, and thus appears to be buried. Fluorescence depolarisation measurements have been used to examine the rotational mobility of the tryptophan in the protein and in the nucleoprotein complex. In the protein alone a single rotational correlation time (phi) of approximately 19 ns is observed, corresponding to rotation of the entire dimeric molecule; in the native nucleoprotein complex with Pfl DNA, a phi of approximately 500 ns is observed, corresponding to a rigid unit of at least 50 subunits. In neither case does the tryptophan exhibit any detectable flexibility on the subnanosecond time scale. PMID- 4039253 TI - A review of mouse mutants as genetic models of epilepsy. AB - Here we review the major inherited convulsive disorders found in mice and discuss their possible relationship to specific clinical seizure disorders in humans. These mouse disorders include audiogenic seizures, the epilepsy (El) mutation, spontaneous seizures, the tottering/learner syndrome, cerebellar abnormalities, myelin disorders, and alcohol withdrawal seizures. Some of these disorders are symptomatic and others are idiopathic. We find that for many major types of epilepsy in humans there exists a similar counterpart in mice. Because the genetic constitution of the mouse is better known and more easily manipulated that that of other mammalian species, the mouse may serve as an excellent animal model for genetic and biochemical studies of epilepsy. PMID- 4039254 TI - Serum hormones during prolonged training of neuromuscular performance. AB - The effects of a 24-weeks' progressive training of neuromuscular performance capacity on maximal strength and on hormone balance were investigated periodically in 21 male subjects during the course of the training and during a subsequent detraining period of 12 weeks. Great increases in maximal strength were noted during the first 20 weeks, followed by a plateau phase during the last 4 weeks of training. Testosterone/cortisol ratio increased during training. During the last 4 weeks of training changes in maximal strength correlated with the changes in testosterone/cortisol (P less than 0.01) and testosterone/SHBG (P less than 0.05) ratios. During detraining, correlative decreases were found between maximal strength and testosterone/cortisol ratio (P less than 0.05) as well as between the maximal strength and testosterone/SHBG ratio (P less than 0.05). No statistically significant changes were observed in the levels of serum estradiol, lutropin (LH), follitropin (FSH), prolactin, and somatotropin. The results suggest the importance of the balance between androgenic-anabolic activity and catabolizing effects of glucocorticoids during the course of vigorous strength training. PMID- 4039255 TI - Influence of heat stress and acclimation on maximal aerobic power. AB - Thirteen male volunteers performed cycle ergometer maximal oxygen uptake (VO2max tests) in moderate (21 degrees C, 30% rh) and hot (49 degrees C, 20% rh) environments, before and after a 9-day heat acclimation program. This program resulted in significantly decreased (P less than 0.01) final heart rate (24 bt X min-1) and rectal temperature (0.4 degrees C) from the first to last day of acclimation. The VO2max was lower (P less than 0.01) in the hot environment relative to the moderate environment both before (8%) and after (7%) acclimation with no significant difference (P greater than 0.05) shown for maximal power output (PO max, watts) between environments either before or after acclimation. The VO2max was higher (P less than 0.01) by 4% after acclimation in both environments. Also, PO max was higher (P less than 0.05) after acclimation in both the moderate (4%) and hot (2%) environments. The reduction in VO2max in the hot compared to moderate environment was not related to the difference in core temperature at VO2max between moderate and hot trials, nor was it strongly related with aerobic fitness level. These findings indicate that heat stress, per se, reduced the VO2max. Further, the reduction in VO2max due to heat was not affect be state of heat acclimation, the degree of elevation in core temperature, or level of aerobic fitness. PMID- 4039256 TI - Noninvasive determination of the anaerobic threshold in canoeing, cross-country skiing, cycling, roller, and ice-skating, rowing, and walking. AB - The relationship between velocity (V) and heart rate (HR) was determined in four canoeists, 42 cross-country skiers, 73 cyclists, nine ice-skaters, 10 roller skaters, 32 rowers, and 20 walkers. The athletes were asked to increase their work intensity progressively, from low to submaximal velocities; HRs were determined by ECG in roller-, ice-skating, and walking, or read on a cardiofrequency meter in canoeing, cross-country skiing, cycling, and rowing. In all the athletes examined the linearity of the V-HR relationship was maintained up to a submaximal speed (deflection velocity, Vd), beyond which the increase in work intensity exceeded the increase in HR. Vd and anaerobic threshold (AT), determined through blood lactate measurements, were coincident in 19 athletes (6 cross-country skiers, 3 cyclists, 2 roller-skaters, 3 rowers, and 5 walkers). Vd was correlated with the average speeds maintained in walking (20 km, n = 13, r = 0.88), cross-country skiing (15 km, n = 20, r = 0.80; 30 km, n = 8, r = 0.82; 12 km, n = 7, r = 0.86; 11 km, n = 7, r = 0.86) and cycling (1,000 m flying-start, n = 68, r = 0.83), thus showing that AT is a limiting factor in these aerobic events. PMID- 4039257 TI - Energy sources in alpine skiing (giant slalom). AB - The energy cost of a giant slalom event was measured in eight skiers of national level. The lap lasted on average 82 s. VO2 was measured during the first, the second and the last third of the lap in different trials and also during recovery from a complete lap. Blood lactate was measured at the end of a lap. From the data obtained it was possible to calculate that: a) VO2, as measured during the lap, would correspond at steady state to 80% of the VO2max of the subjects; b) the total metabolic power delivered during the lap should be equal to about 72 ml O2 X kg-1 X min-1, corresponding to 120% of VO2max of the subjects. Considering the short duration of the trial and the power output delivered during maximal efforts on a bicycle ergometer, it appears that the giant slalom is not a very high energy demanding event. PMID- 4039258 TI - Ventilatory response during incremental exercise tests in weight lifters and endurance cyclists. AB - The effect of a progressively increasing work rate (15 W X min-1) up to exhaustion on the time course of O2 uptake (VO2), ventilation (VE) and heart rate (HR) has been studied in weight lifters (WL) in comparison to endurance cyclists (Cycl) and sedentary controls (Sed). VO2 and VE were measured as average value of 30-s intervals by a semiautomatic open circuit method. VO2max was 2.55 +/- 0.33; 4.29 +/- 0.53 and 2.86 +/- 0.19 l X min-1 in WL, Cycl and Sed respectively. With time and work rate, while VO2 and HR increased linearly, VE changed its slope at two levels. The 1st VE change occurred at a work load corresponding to a mean (+/ SD) VO2 of 1.50 +/- 0.26; 1.93 +/- 0.34; and 1.23 +/- 0.14 l X min-1 in WL, Cycl, and Sed respectively. VO2 values corresponding to the second VE change of slope were 2.18 +/- 0.32 in WL; 3.48 +/- 0.53 in Cycl and 2.17 +/- 0.28 l X min-1 in Sed. The first change of slope might be the consequence of the different readjustment of VO2 on-response and hence of early lactate in the different subjects. The second change seems to be comparable to the conventional anaerobic threshold and is achieved in all subjects when VE vs time slope is 7-10 l X min 1/min of exercise. PMID- 4039259 TI - Effect of exercise training on aortic collagen content in spontaneously hypertensive rats (SHR). AB - We investigated the effects of exercise training on the amount of aortic collagen and systolic blood pressure in spontaneously hypertensive rats (SHR). Ten-week old SHR were trained either by forced treadmill running (26.8 m X min-1 -1 h X day-1, five times a week, 0% incline) or by voluntary running in revolving wheels (7,800 m X day-1 at peak) for 8 weeks. Succinate dehydrogenase (SDH) activity measured as a marker of an endurance training effect was 13% higher (P less than 0.01) in the soleus of forced-exercised animals than in that of sedentary ones. (6.56 +/- 0.17 mumol X g-1 X min-1; mean +/- SEM), whereas SDH activity in that of voluntarily-exercised group was found to be at the same level as in sedentary animals. The systolic blood pressure after training increased by 26.4 in sedentary, 21.1 in voluntarily-exercised, and 33.9 mm Hg in forced-exercised rats, when compared with the value of each group at the beginning of the training program. A significant difference was observed in the increment of blood pressure only between the voluntarily- and forced-exercised groups (P less than 0.05). The amount of aortic collagen in voluntarily-trained rats (96.5 +/- 2.0 mg X g tissue 1, 39.8 +/- 0.7 mg X 100 mg protein-1) was significantly less than that in forced trained rats (P less than 0.05). These results suggest that voluntary, mild exercise training may be more effective in the reduction of collagen accumulation in the aorta associated with the suppression of blood pressure increase than forced, vigorous exercise training in SHR. PMID- 4039260 TI - Red cell 2,3-DPG, ATP, and mean cell volume in highly trained athletes. Effect of long-term submaximal exercise. AB - 20 male elite long distance runners were compared to a control group of blood donors to determine the effect of training on red blood cells. The acute effects of exercise on red cells were investigated in 11 of the runners following a race of 15-30 km. The runners had elevated resting values of red cell 2,3-DPG (P less than 0.05) and mean cell volume (P less than 0.01); blood Hb and ATP were not different from concentrations in the control group. The red cell status of the athletes may be explained by an increased proportion of young erythrocytes in runners. No statistically significant changes in red cell 2,3-DPG, ATP, mean cell volume or blood Hb were found post exercise. PMID- 4039261 TI - Linear increase in optimal pedal rate with increased power output in cycle ergometry. AB - This experiment was designed to estimate the optimum pedal rates at various power outputs on the cycle ergometer. Five trained bicycle racers performed five progressive maximal tests on the ergometer. Each rode at pedal rates of 40, 60, 80, 100, and 120 rev X min-1. Oxygen uptake and heart rate were determined from each test and plotted against pedal rate for power outputs of 100, 150, 200, 250, and 300 W. Both VO2 and heart rate differed significantly among pedal rates at equivalent power outputs, the variation following a parabolic curve. The low point in the curve was taken as the optimal pedal rate; i.e., the pedal rate which elicited the lowest heart rate or VO2 for a given power output. When the optimum was plotted against power output the variation was linear. These results indicate that an optimum pedal rate exists in this group of cyclists. This optimum pedal rate increases with power output, and when our study is compared to studies in which elite racers, or non-racers were used, the optimum seems to increase with the skill of the rider. PMID- 4039262 TI - Plasma FFA responses to prolonged walking in untrained men and women. AB - Gender differences in plasma FFA responses to 90 min of treadmill walking at 35% VO2max were investigated in six men and six women following an overnight fast. The subjects represented average values for maximal oxygen uptake and body fat percentage for age and gender. Mean plasma FFA concentration at 45 and 90 min of exercise were significantly (P less than 0.05) higher for women (0.82 mmol X 1( 1), 0.88 mmol X 1(-1)) than men (0.42 mmol X 1(-1), 0.59 mmol X 1(-1)). Lower R values for women throughout the exercise period indicated a greater percentage fat in total metabolism than for men while the FFA/glycerol results supported greater lipolytic activity for women. The uniformity of percent fat in metabolism for women from rest to exercise showed that FFA release from adipose tissue increased rapidly with the onset of exercise which was not the case for men. Comparison of metabolic data as well as a statistical analysis (ANCOVA) controlling for the influence of VO2max and percentage body fat on FFA plasma concentration suggested that gender differences in FFA responses to prolonged submaximal exercise can be expected to occur in untrained subjects. PMID- 4039263 TI - The effects of cigarette smoking on maximal oxygen consumption and selected physiological responses of elite team sportsmen. AB - The acute and chronic effects of cigarette smoking on selected physiological responses were determined in seven well-trained non-smokers and seven well trained habitual smokers. Non-smokers and smokers did not differ significantly with respect to maximal oxygen consumption (VO2max). The acute effect of smoking two cigarettes immediately prior to a graded exercise stress test on a treadmill ergometer did not significantly alter the VO2max of either group. However, the time taken for non-smokers to reach exhaustion decreased significantly (F = 5.381, P less than 0.05) by a mean of 0.64 min. Smokers recorded lower scores for forced vital capacity (FVC) and forced expiratory volume in the 1st s exhalation (FEV1) than non-smokers. Only the mean FVC of smokers recorded 5 min post exercise was significantly altered by pre-exercise smoking. No differences were found between the resting heart rates (HR) of non-smokers and smokers. Smoking two cigarettes significantly (F = 44.720, P less than 0.01) increased the mean resting HR of smokers and non-smokers by 15.8 beats X min-1 and 15.6 beats X min 1 respectively. No alteration to the exercise HR of either group was found under smoking conditions of the VO2max tests. PMID- 4039264 TI - Dynamics and topography of human temperature regulation in response to thermal and work load. AB - Climatic chamber experiments were carried out with male subjects who were submitted to various rapid temperature changes. All experiments were performed first with the subjects at rest and later at work on a bicycle ergometer. The aims of the study were to obtain quantitative data enabling to determine effects of abrupt thermal load, abrupt work load, and combined load on the topography and the dynamics of temperatures and effectors, and to answer the question whether the effects of combined load may be computed by a linear superposition of pure thermal plus pure work load. Skin temperatures generally respond more directly to abrupt changes of thermal than of work load. This is in contrast to the dynamic behaviour of central temperatures which moreover exhibit the interesting effect of a transient paradoxical response both to the onset of work and of thermal load. Time constants of the dynamics of metabolic heat production are high in response to changes of thermal load as compared to the time constants at the onset and end of work. Generally the time constants of skin temperatures are shorter at rest than at work. Temperature topography changes only to a small extent in exercising subjects. The central temperature increase to combined thermal and work load is not significantly different from the added amount of temperature increases due to pure thermal and to pure work load. This suggests a quasi-linear superposition of both thermal effects and confirms, in accordance with further evidence of this and former studies, the hypothesis that work load does not interfere non-linearly with the regulatory processes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4039265 TI - The pressor response to voluntary and electrically evoked isometric contractions in man. AB - Blood pressure and heart rate changes during sustained isometric exercise were studied in 11 healthy male volunteers. The responses were measured during voluntary and involuntary contractions of the biceps brachii at 30% of maximal voluntary contraction (MVC), and the triceps surae at 30% and 50% MVC. Involuntary contractions were evoked by percutaneous electrical stimulation of the muscle. Measurements of the time to peak tension of maximal twitch showed the biceps brachii (67.0 +/- 7.9 ms) muscle to be rapidly contracting, and the triceps surae (118.0 +/- 10.5 ms) to be slow contracting. The systolic and diastolic blood pressures increased linearly throughout the contractions, and systolic blood pressure increased more rapidly than diastolic. There was no significant difference in response to stimulated or voluntary contractions, nor was there any significant difference between the responses to contractions of the calf or arm muscles at the same relative tension. In contrast the heart rate rose to a higher level (P less than 0.01) in the biceps brachii than the triceps surae at given % MVC, and during voluntary compared with the electrically evoked contractions in the two muscle groups. It was concluded that the arterial blood pressure response to isometric contractions, unlike heart rate, is primarily due to a reflex arising within the active muscles (cf. Hultman and Sjoholm 1982) which is associated with relative tension but independent of contraction time and muscle mass. PMID- 4039266 TI - Serum creatine kinase activity following forearm flexion isometric exercise. AB - The purpose of this study was to compare serum creatine kinase (CK) activity following two forearm flexion isometric exercise regimens differing in work to rest ratio, and examine the CK response to a repeated bout of isometric exercise. Eleven males were tested on two sessions (bouts) spaced 1 week apart. For bout 1, five subjects (group A) performed a forearm flexion isometric exercise consisting of 40 10-s maximal contractions with 20-s inter-trial rests (10:20), while six (group B) performed 40 maximal 10-s contractions with 5-s inter-trial rests (10:5). The increase in serum CK activity following the 10:20 exercise (143%) was significantly greater than that following the 10:5 exercise (52%). The 10:20 exercise was also associated with greater tension generation over trials. One week later, both groups performed a bout of 10:20 exercise. A substantial reduction in the serum CK response was found following this second bout. The data suggest that for bout 1 the isometric exercise associated with the greater overall tension levels resulted in the greater CK response. However, when the 10:20 exercise was repeated 1 week later, a substantial reduction in the CK response was found which was unrelated to the tension generated. PMID- 4039268 TI - A revision of body surface area estimations. AB - The results from the present study indicate that the equation of Dubois and Dubois (1916), now in common use for estimating body surface area, is not the most accurate of those available. Our new equation is based on the measurement of body weight and upper calf circumference only. It accounts for a large percentage of the total variance (88.9%), and has a low standard error of estimate (0.05 m2), which suggests that this equation may be more useful in the estimation of human body surface area than many of the equations previously produced. Direct comparisons of the accuracy of other workers' equations is difficult to assess due to the different methods by which the equations have been produced and expressed. We do not advocate the use of different equations for males and females because the data indicate that the present equation probably applies equally well to both sexes. PMID- 4039267 TI - Changes in venous blood content from active and inactive hindlimb during isotonic exercise. AB - Venous blood samples were obtained from either exercising (n = 9) or nonexercising (n = 8) hindlimb during a progressive isotonic exercise in rabbits anesthetized with urethane and chloralose. Each experimental session consisted of 5-min nonexercise periods alternated with 6-min exercise periods, followed by a 10-min postexercise period. During each exercise period, stimulation of the distal stump of the right sciatic nerve at 1 Hz induced plantar flexions which lifted loads comparable to 2, 5, 8, 30, or 50% of an afterload at which only an isometric tension developed. Free-flowing venous blood samples were obtained before the first exercise period, during the last minute of each exercise period, and 10 min following the last exercise session. Increases in [Na+], [K+] and lactate concentration were obtained in blood from active limbs. Only lactate concentration increased in blood from nonexercising limbs, while [K+] decreased slightly. Inferences concerning the vascular volume response to this protocol would be quite different depending on the blood sampling site. Changes in blood from inactive tissue, further, may indicate only saturation of homeostatic mechanisms which normally compensate for vascular volume alterations initiated in active tissue. PMID- 4039269 TI - Studies of the cellulolytic system of Trichoderma reesei QM 9414. Reaction specificity and thermodynamics of interactions of small substrates and ligands with the 1,4-beta-glucan cellobiohydrolase II. AB - The 1,4-beta-glucan cellobiohydrolase II (CBH II) from Trichoderma reesei QM 9414 catalyses the hydrolysis of the 4-methylumbelliferyl beta-D-glycosides derived from cellotriose, cellotetraose and cellopentaose [MeUmb(Glc)n; n = 3 - 5]. The reaction has been followed by quantitative high-performance liquid chromatography. Specific activity for cellobiose removal at apparent substrate saturation were determined as (0.8 +/- 0.2) min-1 for MeUmb(Glc)3 and (9 +/- 2) min-1 for MeUmb(Glc)4. The enzyme showed a deviant specificity with MeUmb(Glc)5 as substrate. Two chromophoric products were formed simultaneously [MeUmb(Glc)3 and MeUmb(Glc)2] with turn-over numbers (17 +/- 4) min-1 and (21 +/- 6) min-1, respectively. Methylumbelliferyl beta-glucoside (MeUmbGlc) and the corresponding cellobioside [MeUmb(Glc)2] were used in equilibrium binding experiments. Both ligands yielded one binding site per molecule of Mr = 54000 upon forced flow dialysis (diafiltration). The association constants found were in fair agreement with those determined from MeUmb fluorescence quenching titrations. Quenching was total at all temperatures investigated for MeUmb(Glc)2, whereas for MeUmbGlc it increased from 80% to 100% between 2 degrees C and 20 degrees C. The association constants fitted linear van't Hoff plots in both cases. MeUmb(Glc)2 and MeUmbGlc were also used as indicator ligands to determine the association constants and thermodynamic parameters of several non-chromophoric ligands of CBH II. The binding of glucose increased the affinity for MeUmb(Glc)2 whereas it displaced MeUmbGlc from its complex. A putative binding site of the CBH II containing four subsites can be proposed. The thermodynamic data for methyl beta-D glucopyranoside and cellobiose as ligands also point at an extended binding site. PMID- 4039271 TI - Cholera toxin enhances factor-dependent colony growth of murine mast cell progenitors. AB - Mast cell colonies were observed when mouse spleen or bone marrow cells were cultured in the presence of medium conditioned by concanavalin-A-stimulated spleen cells, indicating that the medium contains the factor(s) necessary for the formation of these colonies. This factor-dependent colony growth of mast cell progenitors was enhanced by cholera toxin and prostaglandin E, which act on cellular growth mainly by elevating the intracellular cyclic-AMP level. The effect of the toxin was neutralized by preincubation of the toxin with GM1 ganglioside, the receptor substance for cholera toxin, suggesting that cholera toxin exerts its action through GM1 gangliosides present on mast cell progenitors. The toxin B subunit, which binds to GM1 ganglioside but does not elevate intracellular cyclic AMP level, did not affect the colony growth of mast cell progenitors. From these results, it is suggested that intracellular cyclic AMP levels may be involved in colony growth of mast cell progenitors. PMID- 4039272 TI - Regulation of [3H]forskolin binding to human platelet membranes by GppNHp, NaF, and prostaglandin E1. AB - Displaceable binding of [3H]forskolin to human platelet membranes can be detected in the presence of magnesium. There is an increase in the number of [3H]forskolin binding sites when membranes are incubated with GppNHp or NaF in the presence of magnesium. Prostaglandin E1, which stimulates human platelet adenylate cyclase, does not affect the binding of [3H]forskolin in the absence of GppNHp. However, the dose-response curve for the GppNHp-dependent increase in [3H]forskolin binding sites is shifted to lower concentrations in the presence of prostaglandin E1. Prostaglandin E1 potentiates the effect of GppNHp on [3H]forskolin binding most likely by facilitating the binding of the guanine nucleotide at the stimulatory quanine nucleotide regulatory protein of adenylate cyclase. PMID- 4039270 TI - omega-123I-hexadecanoic acid metabolic probe of cardiomyopathy. AB - The utility of omega-123I-hexadecanoic acid myocardial scintigraphy as a metabolic probe of cardiomyopathies was investigated. Sixteen patients with a variety of cardiomyopathies and myopathies that involve cardiac muscle and ten volunteers were imaged in the postabsorptive state in a 40 degrees LAO projection after a standard dose of omega-123I-hexadecanoic acid. An elimination T1/2 was calculated from the left ventricular myocardial time-activity curve. An uptake index, corrected for chest wall attenuation, was also computed in 7 of 10 volunteers and 8 of 16 patients. Of the 16 patients, only 2 had distinctly abnormal omega-123I-hexadecanoic acid myocardial tracer kinetics. The first patient had a metabolic disorder of which carnitine deficiency was one component. The second patient had endocardial fibroelastosis, a process which has been linked to disorders which deprive the myocardium of oxygen and energy. Therefore, the cardiomyopathy may have been caused by some abnormality of cardiac metabolism other than carnitine deficiency. Although of limited utility in the overall cardiomyopathic population, omega-123I-hexadecanoic acid myocardial scintigraphy should be further investigated as a screening test for carnitine deficiency and related metabolic abnormalities in patients at risk. PMID- 4039273 TI - Two separate tyrosine protein kinases in human platelets. AB - Tyrosine protein kinase activities were detected in the cytosolic fraction (PC TPK) and the particulate fraction (PM-TPK) in human platelets using the synthetic peptide, E11G1 (Glu-Asp-Ala-Glu-Tyr-Ala-Ala-Arg-Arg-Arg-Gly) as a substrate. PC TPK and PM-TPK were different in substrate specificities, divalent cation requirements and apparent Mr values. These results strongly suggest that in platelets there exist at least two separate tyrosine protein kinases; one is present in cytosol and the other might be associated with membranes. PMID- 4039274 TI - Inhibition of human sperm penetration into zona-free hamster oocytes by proteinase inhibitors. AB - The potential role of serine proteinase in the penetration of human spermatozoa into denuded (zona-free) hamster oocytes was investigated. Aryl 4 guanidinobenzoates (10(-4) to 10(-6) M) and 4-aminobenzamidines (10(-3) and 10( 4) M) decreased oocyte penetration when present throughout the assay system. More detailed studies with 8-quinolyl 4-guanidinobenzoate showed that this inhibitor also caused a large decrease in the penetration rate even when only present during the preincubation period of the spermatozoa to induce capacitation. Much smaller decreases were observed when this inhibitor was only present during sperm/egg incubation. By contrast, 4-aminobenzamidine caused a large decrease in the penetration rate when present during sperm/egg incubation but a much smaller one when present during the sperm's preincubation period. The primary action of the inhibitors was not due to a visible effect on sperm motility or forward progression, or to an effect on the oocyte, although treatment of oocytes with inhibitor caused a small decrease in penetration. Inhibition of sperm binding to the oolemma occurred also at times, but this was not directly correlated to the decrease in oocyte penetration. The results are consistent with the fact that a serine proteinase, presumably acrosin, is important for the capacitation, acrosome reaction, and/or oocyte penetration of human spermatozoa. The synthesized aryl 4-guanidinobenzoates are of interest as contraceptive agents because they possess phenols approved by the Food and Drug Administration (United States) for human use and should be relatively nontoxic. PMID- 4039275 TI - Reproductive development in male deer mice exposed to aggressive behavior. AB - Male deer mice (Peromyscus maniculatus bairdii) were reared in a long photoperiod and housed individually from 3 weeks of age until they were killed 2, 4, or 6 weeks later. Males that were exposed to aggressive females for 2 min, three times per week, were of normal body weight and healthy, but had smaller reproductive organs than did males exposed to a control treatment. Reproductive development in male deer mice is responsive to at least two classes of social stimuli: pheromones and aggressive behavior. PMID- 4039276 TI - Toxicity of cyclohexanone oxime. II. Acute dermal and subchronic oral studies. AB - Dermal exposure of rabbits to cyclohexanone oxime (CHO) for 24 hr at 0, 0.8, 2, and 5 g/kg caused dose-related reticulocytosis on the day after dosing as well as a decrease in hemoglobin in the 5-g/kg females 7 days postdosing. Gavage of rats 5 days a week for 13 weeks at levels of 0, 0.25, 2.5, and 25 mg/kg resulted in a dose-related decrease in erythrocyte number, hemoglobin, and hematocrit, with an accompanying increase in circulating reticulocytes and nucleated erythrocytes, in both sexes. Also seen were corneal opacities and an increased incidence of Howell Jolly bodies. Results suggested an increased erythropoiesis in the spleen and bone marrow. The data from satellite groups terminated at 30 and 60 days revealed no effect at the lower test level, but results from the end of the study showed a clear cumulative dose response down to the 0.25-mg/kg level. Males were affected earlier and at lower doses than females. These results, along with those of a subacute study with a recovery period, suggest that CHO induces an oxidative attack on erythrocytes which appears reversible upon cessation of exposure. PMID- 4039277 TI - Annual and diurnal cycles in plasma testosterone and thyroxine in the male green sea turtle Chelonia mydas. AB - Male plasma testosterone (T) and thyroxine (T4) were monitored over several annual cycles in a captive breeding colony of green sea turtles, Chelonia mydas. Daily and annual water temperatures varied by only approximately 1 and 3 degrees, respectively. A pronounced season cycle in plasma T was evident in the population as a whole and in individual animals: plasma T was at a nadir (approximately 3 ng/ml) in September-November and then increased progressively to a peak (27-39 ng/ml) in April; levels began declining immediately thereafter, coincident with the onset of copulatory behavior. By contrast, plasma T4 remained uniform (approximately 9 ng/ml) throughout the year and, thus, could not readily account for the decline in androgen levels. Plasma hormones were relatively stable over a 24-hr period at three times a year, and there was a correlation for individual plasma T levels sampled in April and May. Thus, limited sampling should allow identification of seasonal rhythms and individual variability in plasma T levels. Testis mass and spermatogenic activity were significantly greater in January than in September; i.e., spermatogenesis and androgen secretion were not "uncoupled." Copulatory activity began in April but did not peak until May-June, after plasma T had significantly declined. However, there was a significant (but weak) correlation between individual peak levels of plasma T (i.e., in April) and the quantitative level of mating activity (time spent mounting and number of mates) measured for the entire subsequent season. Thus, green turtles do not exhibit the "postnuptial" type of testis cycle typical of many temperate-zone turtles, and the levels of plasma androgen may be important for initiating and maintaining sex behavior, although they are not tightly linked during the mating season. PMID- 4039278 TI - Diel variations in arginine vasotocin content of goldfish brain and pituitary: effects of photoperiod and pinealectomy. AB - Arginine vasotocin (AVT) content was determined in the telencephalon, the hypothalamus, and the pituitary gland of sham-operated and pinealectomized goldfish subjected to 20 degrees and 12/12LD or 24DD photoperiods in winter or spring. The tissues collected at 1000 or 2200 hr were homogenized and extracted in acetic acid. Hypothalamic and telencephalic AVT content, determined by radioimmunoassay, fluctuated throughout the light-dark cycle; AVT content was higher at 2200 than at 1000 hr under the 12/12LD photoperiod. No fluctuations were detected in pituitary AVT content. Telencephalic AVT did not fluctuate under constant darkness, and hypothalamic AVT increased and pituitary AVT decreased compared to the AVT content detected in the 12/12LD groups. No significant effects of pinealectomy or season on AVT levels in the telencephalon, hypothalamus, and the pituitary were evident. The results indicate that AVT content within the preoptico-neurohypophyseal system of the goldfish fluctuate within 24-hr periods and that photoperiod has an effect on the pattern of these fluctuations. The photoperiodic influences do not seem to be mediated by the pineal organ. PMID- 4039279 TI - The effect of prostaglandin F2 alpha analog on the plasma concentration of progesterone in the bandicoot, Isoodon macrourus (Marsupialia:Peramelidae), during lactation. AB - Prostaglandin F2 alpha (PGF) analog was administered to bandicoots during lactation to determine whether PGF2 alpha is involved in the regression of the marsupial corpus luteum. The concentration of progesterone in the plasma, and the morphology of the corpus luteum were monitored following PGF analog treatment. When the drug was administered early in lactation, there was no apparent change in luteal function. However, when PGF analog was administered on Days 30 and 31 of lactation an immediate decrease in plasma progesterone concentration to 0.1 ng/ml was observed and regression of the corpora lutea was observed by Day 36. The corpus luteum of numerous eutherian species is resistant to the luteolytic effects of prostaglandin F2 alpha in the early luteal phase. The corpus luteum of the bandicoot appears to be resistant in a similar manner during early lactation. PMID- 4039280 TI - Presence of immunoreactive melatonin in different tissues of the pigeon (Columba livia). AB - The distribution of melatonin was studied at midday and midnight in pigeon plasma, pineal, hypothalamus, eyes, Harderian glands, and duodenum. Tissue samples were homogenized, extracted with chloroform, evaporated, and measured by our melatonin radioimmunoassay (RIA). All the extracts gave dilution curves parallel to that of synthetic melatonin and eluted in reverse-phase high performance liquid chromatography (HPLC) as synthetic melatonin indicating that the immunoreactivity was due to endogenous melatonin in pigeon tissues. Melatonin was found to be present in pigeon plasma, pineal, hypothalamus, eyes, Harderian glands, and duodenum. In all tissues it had a clear diurnal variation with low levels at midday and high levels at midnight. The highest amounts of melatonin were found in the eyes, duodenum, and the pineal so that extrapineal melatonin exceeded pineal melatonin. Further studies are needed to evaluate the significance of extrapineal melatonin. PMID- 4039281 TI - [Effect of cell respiration inhibitors on the formation of structural mutations in human lymphocytes irradiated at different stages of the mitotic cycle]. AB - Human lymphocytes were irradiated by 60Co gamma-rays after 0, 10, 20, 35, 45, 48 and 49.5 h of incubation. Immediately after irradiation sodium cyanide, sodium fluoride or monoiodoacetic acid was given for 2.5 h. Non-irradiated cells were subjected to the same treatments. Chromosomal aberrations were analysed in metaphase cells of the first mitosis. When administered alone, all chemicals increased the frequency of chromatid aberrations. The special analysis showed that these chemicals were not mutagens in a strict sense, as the observed increase of aberration frequency was due to inhibition of repair processes, which increased the probability of manifestation of spontaneous changes (so-called "pseudomutagenesis"). The same chemicals increased the frequency of radiation induced aberrations during two periods of the mitotic cycle, namely, in the end of the G1 stage and in the G2 stage. It has been recently shown that the inhibitor of DNA synthesis, 5-fluorodeoxyuridine, increased the frequency of radiation-induced aberrations during the same periods. It follows that the process of repair proceeding during these periods requires both DNA synthesis and energy supply. PMID- 4039282 TI - [Action potential conduction velocity along the caudal and tibial nerves in rat strains selected for excitability of the neuromuscular system]. AB - The study was performed on 2 lines of rat selected for high (H) and low (L) excitability threshold of the nervous-muscle apparatus. H-line rats have higher values of spike conduction velocity in caudal and tibial nerves, as compared to those obtained in L-line rats. It is suggested that behavioral differences between these two lines of rat may be connected with changes of neurological characters both of peripheral and central nervous system, as a result of selection. PMID- 4039283 TI - [Genetic nature of atrophic rhinitis in swine. II. Cytogenetic research]. AB - This work is concerned with the problem of the nature of the atrophic rhinitis in swine. Our study demonstrates that the filter-passers when injecting intranasal provoke catarrhal rhinitis in sucking-pigs and rabbits and the disease lasts 10 12 days. Guinea-pigs and white mice show no disease symptoms after injection. After four passages of filter-passers through sucking-pigs, the pathogenic properties do not restore. The sucking-pigs and laboratory animals show no changes in organs and in nasal cavity. The findings of cytogenetic and allergic investigations indicate genetic aspects of this disease. To eliminate atrophic rhinitis, it is necessary to reveal heterozygotes, carry out experimental matings and analysis of hybrids. To date, a recessive gene is considered to mediate the disease. To obtain healthy offspring, animals heterozygous for this gene should be bred. PMID- 4039284 TI - [Mathematical modeling of the dynamics of the intensity of the mutation process. I. Formulation of the task and the general model]. AB - Methodology is devised to construct dynamic models of the mutation process intensity under quasi-stationary environmental conditions and limited experimental information. Laws of distribution of unknown parameters of dynamic models and prognostic values of inherited pathology frequencies were determined for the cases of normal distribution with zero mathematical expectancy and constant dispersion of casual environmental influence. Given is the algorithm of dynamic model construction on frequencies of inherited pathology, using experimental data and on the basis of determination of permissible intervals for their prognostic values. PMID- 4039285 TI - Syndrome of inappropriate antidiuretic hormone secretion during cis dichlorodiammineplatinum therapy in a patient with an ovarian carcinoma. AB - Case report of syndrome of inappropriate antidiuretic hormone. (SIADH) developing in a patient treated with cis-dichlorodiamine platinum for an endometrioid carcinoma of the ovary. This syndrome has not been reported with this tumor type and no other drugs known to cause SIADH were administered. PMID- 4039286 TI - High-dose metoclopramide as an antiemetic in patients receiving cis-platinum based combination chemotherapy. AB - Thirty-seven patients with advanced malignancies, who received cis-platinum-based combination chemotherapy, were evaluated for the antiemetic efficacy of high-dose metoclopramide. Most of the patients suffered from ovarian carcinoma. The dose of metoclopramide was 7.5 or 10 mg/kg per course. A total of 69 courses were given to 37 patients and in 22% of the courses, nausea and vomiting were eliminated altogether. In an additional 48% of the courses, a partial protection from chemotherapy-induced emesis was evident. No serious side effects were observed. The administration of high-dose metoclopramide is recommended for prevention of cis-platinum chemotherapy-induced emesis. PMID- 4039287 TI - Development of methotrexate-resistant human choriocarcinoma cells in culture. AB - A human choriocarcinoma cell line, HCCM-5, was fed with medium containing increasing concentrations of methotrexate (MTX). The initial MTX concentration, 10(-9) M which reduced the [3H] thymidine incorporation into DNA, was raised from 2- to 2.5-fold successively. After about 36 weeks of feeding, the cells became resistant to 5 X 10(-7) M which produced complete inhibition of the parent HCCM-5 cell growth. The parent line and its MTX-resistant subline (HCCM-5MTXr) had almost the same population doubling time. There were no apparent differences in morphology and human chorionic gonadotropin secretion between the two cell lines. The development of resistance was accompanied by a 10-fold decrease in the 3H-MTX uptake and a 5-fold elevation of the intracellular dihydrofolate reductase (DHFR) activity. The impairment of MTX transport in HCCM-5MTXr cells continued after transferring the HCCM-5MTXr cells into MTX-free medium, whereas the DHFR activity returned to the level found in the HCCM-5 cells. These results indicate that the MTX resistance acquired in choriocarcinoma cells chiefly involves the impaired transport of MTX and continues after the deprivation of the drug. PMID- 4039288 TI - [Animal experiments of neuroma treatment with histoacryl]. AB - A neuroma arises due to uncoordinated growth of axis cylinders in proliferated granulation tissue. An intact perineurial tube prevents further growth of the funiculi. Animal experiments were designed to close the perineurial tube such that it was impervious to water. Earlier experiments with purse string suture of the perineurial tube or closure with Histoacryl were not always successful. After severance of the sciatic nerve of the rat and shortening of the axons, the epineurial tube was plugged with Histoacryl blue and closed so that it was impervious to water. The preparations were checked optically and histologically. The results were promising, so that this technique was applied clinically. PMID- 4039289 TI - [Chronopharmacological study of physical dependence on morphine in rats]. AB - Relationship between withdrawal time or naloxone injection time and withdrawal signs were examined in morphine-treated rats. Sixty-five rats were treated chronically with morphine-admixed food (1 mg/g food) for 7 days and were divided into 13 groups. The rats of 4 groups were abruptly withdrawn from morphine, and the rats of another 4 groups were given naloxone (3 mg/kg, s.c.) at 20:00 on the 8 th day and 2:00, 8:00 and 14:00 on the 9 th day after the morphine administration, respectively. Withdrawal signs were observed at intervals of 2 hr. After each naloxone injection, abnormal behaviors were observed for 60 min, and body weight was measured for 3 hr at intervals of 15 or 30 min. In the withdrawal test, weight loss at 24 hr after withdrawal in each group was approximately 10%, and there was no difference between each group. However, the body weight of non-treated rats and morphine-treated rats increased during the night period (20:00-8:00) and decreased during the daytime (8:00-20:00). Therefore, body weight reached the minimum at 20:00, and then this time is appropriated for withdrawal. In the naloxone test, withdrawal signs in the night period were more potent than that in the daytime. The withdrawal signs induced by naloxone at 8:00 showed the maximum magnitude. Plasma morphine levels in rats treated with morphine-admixed food were high in the night period and low in the daytime. These results suggest that the magnitude of naloxone-precipitated withdrawal signs depends on the amount of morphine in the plasma. PMID- 4039290 TI - [Hypertrophic obstructive cardiomyopathy: surgical treatment and results]. AB - The natural history of hypertrophic obstructive cardiomyopathy is characterized, in particular, in younger patients by sudden cardiac death, in the majority of patients by progressive congestive heart failure [14, 26, 27, 33-36]. With the aid of beta-adrenergic receptor blockers, calcium channel blockers and antiarrhythmic agents the clinical outlook for most of the patients can be improved [17, 19, 23, 28]. Patients who do not respond to medical treatment can be regarded as possible candidates for surgical revision of the left ventricular outflow tract. In consideration of surgical treatment, two morphologic and hemodynamic forms of the disease must be differentiated: the typical subaortic muscular hypertrophy in the region of the outflow tract and the atypical, more mid-ventricular muscular hypertrophy with systolic entrapment of a distal portion of the ventricle in which frequently a typical subaortic hypertrophy also may be present [15, 43]. As a result of septal subvalvular hypertrophy which may substantially compromise left ventricular ejection during systolic contraction, in hypertrophic obstructive cardiomyopathy there is a deviation of the left ventricular major axis, dyscoordination in the sequence of contraction, hypertrophy of the left ventricular walls, diminished diastolic compliance and, to a varying extent, mitral regurgitation. Diagnostically useful findings are a mid-systolic murmur at the aortic valve, bisferiens carotis pulse, systolic pressure gradient between the left ventricle and the aorta and a postextrasystolic paradoxical pressure response. Echocardiographically, asymmetric septal hypertrophy, systolic anterior motion of the anterior mitral valve leaflet, premature mid-systolic closure of the aortic valve and an enlarged left atrium will be detected. Surgical intervention is indicated for patients with class III clinical symptoms (NYHA) not amenable to medical treatment and pressure gradients between left ventricle and aorta, at rest or postextrasystolically, in excess of 50 mm Hg. An overview of the variety of surgical approaches and procedures employed for hypertrophic obstructive cardiomyopathy is provided by Table 1. From initial attempts to eliminate the outflow tract obstruction by myotomy, the subvalvular myectomy was developed in which an about 1 cm wide section of muscle is resected; this procedure can be carried out from a transaortic, transatrial or transventricular approach [4, 9, 21, 22, 24, 38, 39, 47]. Under the assumption that the anterior motion of the anterior mitral valve leaflet contributes to systolic obstruction, some authors recommended reconstructive procedures or replacement of the mitral valve.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 4039291 TI - Indices of left ventricular systolic function derived by computer analysis of digitised M-mode echocardiograms. AB - In order to determine the value of computer-assisted analysis of echocardiograms we digitised 980 M-mode studies in normal subjects and patients with pressure and volume overload and heart muscle disease to derive left ventricular dimensions (D), peak systolic rate of change of dimension, normalized for instantaneous dimension (dD/dt/D), mean velocity of circumferential fiber shortening (mean Vcf) and percentage fractional shortening (%FS). The systolic phase indices which, in these patients averaged greater than normal in those with aortic stenosis and hypertrophic cardiomyopathy and lower than normal in those with aortic regurgitation, mitral stenosis and dilated cardiomyopathy, were closely related to each other in all categories of patients. Measurement of % FS appears to describe left ventricular function as well as the more complex indices (mean Vcf, peak dD/dt/D). PMID- 4039292 TI - [Noninvasive and invasive study procedures in hypertrophic cardiomyopathy]. AB - Noninvasive and invasive diagnostic procedures permit a differentiated insight into the hypertrophic cardiomyopathies. For a better understanding of the disease, classification according to morphologic and functional criteria was introduced. It has proven useful to subdivide hypertrophic obstructive cardiomyopathy into two types: idiopathic hypertrophic subaortic stenosis and midventricular obstruction; hypertrophic nonobstructive cardiomyopathies can be subdivided into two forms designated as asymmetrical septal hypertrophy and apical hypertrophy. Combined forms can also be recognized. With a high degree of accuracy, it is possible to differentiate between hypertrophic obstructive and hypertrophic nonobstructive cardiomyopathy by means of noninvasive procedures such as clinical examination, electrocardiography, mechanocardiography and, above all, echocardiography. Experience has shown that two-dimensional echocardiography, in particular, has assumed an especially important role, the value of which approaches that of cardiac catheterization. In this overview, emphasis is placed on the diagnostic peculiarities of idiopathic hypertrophic subaortic stenosis as well as the findings in midventricular obstruction and apical hypertrophy. In the past, only relatively little attention has been focused on the latter subgroups even though they can be diagnosed with a high degree of accuracy with noninvasive as well as invasive procedures. PMID- 4039293 TI - [Drug treatment of hypertrophic cardiomyopathy]. AB - Both, beta-receptor blocking agents and calcium-antagonists have been proven to be very effective in the treatment of idiopathic hypertrophic cardiomyopathy. In the vast majority of patients they lead to a significant reduction of the predominant clinical symptoms--angina and dyspnea--or even abolish them. Since beta-blockers primarily act on the contractile behaviour of the left ventricle they are especially suited in the obstructive form of the disease where they reduce outflow tract obstruction. In contrast, calcium-antagonists seem to mainly influence diastolic muscle mechanics by increasing diastolic distensibility, and thus may be indicated in the nonobstructive forms of hypertrophic cardiomyopathy. In cases with severe, life-threatening arrhythmias especially if associated with syncope, an antiarrhythmic therapy is mandatory. PMID- 4039294 TI - [Appraisal of ultradian components in the ethosecretogram of rat]. AB - An ethosecretogram, which illustrates phase relation between animal's behavior and plasma hormone levels, was constructed in conscious rats. A catheter was placed into the right atrium in male rats at least 2 days prior to blood sampling. Plasma corticosterone levels were monitored individually through the catheter every 5 min over a period of several hours under freely moving conditions on an Animex which records spontaneous locomotor activity. Furthermore, phase relation of ultradian components in both variables were analyzed in separate series of experiments. Results obtained are as follows; Both locomotor activity and plasma corticosterone level in the ethosecretogram exhibited ultradian components with a 60-90 min cycle. Ultradian components of both variables were phase-locked, the bursts of locomotor activity preceding the hormone peak by 15 min. As to the type of locomotor activity, feeding and grooming were significantly correlated with a subsequent hormone elevation, whereas drinking was not. Feeding-induced hormonal elevation was greater in response at dark phase (especially at midnight) than at light phase. Drinking of glucose solution induced a hormone elevation similar to feeding, whereas intravenous infusion of glucose solution did not. Feeding-induced hormone elevation was not abolished even when the vagi were effectively cut at a subdiaphragmatic level. It was assumed that the information from digestive organs to the CNS was not transmitted neurally via the sensory vagal nerves, but humorally via a humoral factor(s) released from digestive organs. PMID- 4039295 TI - Body composition in adopted and biological siblings. PMID- 4039296 TI - Angled aorta ("sigmoid septum") as a cause of hypertrophic subaortic stenosis. AB - Review of the hearts of seven patients in whom hypertrophic obstructive cardiomyopathy had been diagnosed by the usual clinical and morphologic criteria revealed diminished angles between the interventricular septa and ascending aortas in three cases. The angles in these three hearts were 90 to 110 degrees, as compared with a mean value of 145 degrees in the other four hearts with hypertrophic obstructive cardiomyopathy and 140 +/- 14 degrees in 55 control hearts. None of the patients with hypertrophic subaortic stenoses and angled aortic roots died of the heart disease, and none had either asymmetric ventricular hypertrophy or evidence of familial cardiomyopathy. It is proposed that in patients with angled aortic roots and left ventricular hypertrophy, subaortic obstruction may develop due to narrowing of the left ventricular outflow tract, resulting in clinical and morphologic findings of hypertrophic obstructive cardiomyopathy. In hearts with angled aortic roots the top of the ventricular septum is tipped toward the mitral valve, rather than tapered toward the aorta, as in normal hearts. This configuration narrows the outflow tract of the left ventricle and can result in systolic anterior motion of the mitral valve, the illusion of asymmetric septal hypertrophy when studied by M-mode echocardiography, a subaortic pressure gradient, and a subaortic endocardial plaque. This less serious form of hypertrophic subaortic stenosis should be distinguished from other forms of hypertrophic obstructive cardiomyopathy. PMID- 4039297 TI - Congenital stenotic arteriopathy with medial dysplasia. AB - An unusual, uniformly stenotic arteriopathy involving the aorta and its major branches, the pulmonary trunk, and the left and right pulmonary arteries was found in association with a persistent common atrioventricular canal in an otherwise normal stillborn female infant. The uniform arterial thickening was due to hyperplastic medial elastic laminae, which were in an orderly arrangement in the inner two thirds but dysplastic in the outer third of the media of the arteries. PMID- 4039298 TI - The role of DNA synthesis in peptidoglycan-induced generation of immunoglobulin secreting cells in mice and humans. AB - The requirement for DNA synthesis in peptidoglycan (PG)-induced activation of polyclonal antibodies has been studied. Inhibition of DNA synthesis with mitomycin C or hydroxyurea at the initiation of the cultures inhibited generation of over 90% of IgM- and IgG-secreting cells in PG-stimulated mouse splenocytes and of over 99.9% of IgM-, IgG- and IgA-secreting cells in PG-stimulated human peripheral blood lymphocytes. Inhibition of DNA synthesis 2 to 4 days after initiation of PG-stimulated cultures (in both mice and humans) caused an immediate decline in the numbers of Ig-secreting cells. These results demonstrate that the magnitude of PG-induced polyclonal antibody response depends on continued DNA synthesis and proliferation of Ig-secreting cells, and indicate that IgM-, IgG- and IgA-secreting cells in polyclonal activation may be actively cycling cells. PMID- 4039300 TI - The distribution of oestradiol in plasma from postmenopausal women with or without breast cancer: relationships with metabolic clearance rates of oestradiol. AB - The distribution of oestradiol in plasma from postmenopausal women with or without breast cancer has been measured and related to the metabolic clearance rates of oestradiol (MCR-E2). All measurements were carried out preoperatively. No difference in the free fraction of oestradiol was found between women with breast cancer (1.8 +/- 0.4%, mean +/- SD) and normal women (1.6 +/- 0.3%). Approximately 40% of oestradiol in plasma was bound to albumin with 60% bound to sex hormone binding globulin (SHBG), but values were similar for women with or without breast cancer. Concentrations of total unconjugated oestradiol and free oestradiol (2.4 +/- 0.5 ng/100 ml and 44 +/- 12 pg/100 ml respectively, mean +/- SD, n = 9) were significantly higher in plasma from postmenopausal women with breast cancer compared with levels in plasma from normal postmenopausal women (1.8 +/- 0.5 ng/100 ml and 27 +/- 10 pg/100 ml, n = 8). A significant correlation was found between the free oestradiol fraction and MCR-E2 (r = 0.53, p less than 0.05). Correlations were also found between the fractions of oestradiol bound to albumin and MCR-E2 (r = 0.45). From correlations between the binding capacity of SHBG and MCR-E2 it appears that, for a given level of SHBG, MCR-E2 may be higher in women with breast cancer. PMID- 4039299 TI - Nonimmune binding of equine immunoglobulin by the causative organism of contagious equine metritis, Taylorella equigenitalis. AB - This study identifies nonimmune binding of equine immunoglobulin by the causative organism of contagious equine metritis. Immunoglobulin binding to the bacterium was strongest for immunoglobulin G (IgG) and less for IgM; IgA was not bound. Binding of equine IgG was inhibited by human IgG, but not by IgG of domestic animals. Immunoglobulin binding by the bacterium appeared to be directed towards an epitope in the hinge region of the immunoglobulin molecule. PMID- 4039302 TI - Three different types of alpha-interferons alter naloxone-induced abstinence in morphine-addicted rats. AB - The opiate abstinence syndrome represents a fundamental feature of the addictive process, with the degree of addiction being directly correlated to the intensity of withdrawal. Therefore, the discovery of substances capable of attenuating withdrawal signs may provide insights into the dynamics of opiate addiction. The present study demonstrates that three different types of alpha-interferons modify the behavioral signs associated with naloxone-induced abstinence in rats addicted to morphine. These observations suggest that opiate addiction may, in part, be due to an immune response in that immunomodulators (interferon) are capable of altering the naloxone-induced abstinence syndrome in morphine-dependent rats. PMID- 4039301 TI - Basal cell carcinoma following chronic otitis media. PMID- 4039303 TI - Platinum based combined modality approach for locally advanced head and neck carcinoma. AB - Radiation therapy delivered soon after cisplatin administration is used for the treatment of advanced head and neck cancer. A radiation dose of 4800 cGy is given in standard fractions, followed by clinical evaluation and either surgical resection or an additional radiation dose of 2000 cGy. The histopathology of the surgical specimens from 21 patients undergoing resection in this protocol is compared with the corresponding clinical evaluation of tumor response. A significant number of both false negative and false positive clinical assessments are revealed by this comparison. In addition, it appears that local control of bulky head and neck cancer is approached by 4800 cGy combined soon after cisplatin. Discussion of the likely bases for this apparently favorable clinical interaction between cisplatin and radiation is presented. PMID- 4039305 TI - Illegal distribution of animal drugs. PMID- 4039304 TI - Radiosensitization of EMT6 cells by four platinum complexes. AB - The greatest research effort in producing radiation sensitizers has been directed toward organic compounds. However, platinum complexes also have radiosensitizing capabilities, perhaps because they bind to DNA. The compound described here are dichloro complexes of bivalent platinum with one or two potentially radiosensitizing ligands. The radiosensitization of oxygenated and hypoxic exponentially growing EMT6 cells in vitro was measured. The dose modifying factors obtained with 200 microM and 400 microM trans-bis(2 nitroimidazole)dichloroplatinum II (NIPt) in hypoxic cells were 1.5 and 2.1, respectively. For trans-bis(2-amino-5-nitrothiazole)dichloroplatinum II (Plant) under the same conditions, the dose modifying factor was 1.5 at 200 microM and 1.8 at 400 microM. Neither compound sensitized oxygenated cells when tested similar protocols. Unlike the trans complexes, (1,2-diamino-4 nitrobenzene)dichloroplatinum II (Plato) was cytotoxic toward the hypoxic cells in the absence of X rays. The time course of cytotoxicity for 100 microM Plato in exponentially growing cells showed rapid killing of hypoxic cells, and much less toxicity toward oxygenated cells. In radiosensitization studies, dose modifying factors of 1.6 and 2.0 were found with 200 microM and 400 microM Plato in hypoxic cells. The compound did not sensitize aerobic cells. The well-known platinum complex cis-dipyridinedichloroplatinum II (PyPt) represents a cis-platinum heterocyclic aromatic complex that does not have a nitro-functionality. The dose modifying factor obtained with 400 microM PyPt in hypoxic cells was 1.7. On a molar basis, the nitro-functional platinum complexes appear to be more effective as hypoxic cell radiosensitizers than the corresponding free ligands. PMID- 4039306 TI - Phycomycosis caused by Basidiobolus haptosporus in two horses. AB - Basidiobolus haptosporus was isolated from a horse with a rapidly progressive ulcerative lesion of the ventral midline. The pathologic findings of an irregular line of yellow material composed of hyphae, eosinophils, and granulomatous inflammation between the superficial edematous tissue and the underlying muscle, and hyphae in tissue sections intimately surrounded by granular eosinophilic cuffs were considered diagnostic for this and one other case diagnosed retrospectively. Both horses were successfully treated by surgery and potassium iodide. PMID- 4039307 TI - Feedlot performance of hysterectomized and ovariectomized heifers. AB - Seventy-five crossbred heifers (mean weight 304 kg) were stratified by weight and source and placed in eight pens. Four duplicate treatments were randomly assigned to pens as follows: (1) intact-control (n = 19), (2) intact + melengestrol acetate (MGA, n = 20), (3) hysterectomy (n = 17) and (4) ovariectomy (OVX, n = 19). All heifers were preconditioned for 2 mo before beginning the finishing study. Surgery was performed through a high lumbar incision approximately 3 wk before the finishing study began. Group 2 heifers were fed .4 mg X head-1 X d-1 MGA. Blood samples were collected at 28-d intervals throughout the 112-d finishing phase. Ovaries were collected at slaughter and carcass data were obtained 24 h after slaughter. On d 112, progesterone was higher (P less than .05) in hysterectomized heifers than in other treatment groups. Serum progesterone concentration was nondetectable (less than .35 ng/ml) in OVX and MGA heifers. There were no differences (P greater than .05) in feed efficiency or carcass characteristics among the four treatments. Hysterectomized and MGA heifers had similar (P greater than .05) average daily gains, which were higher (P less than .15) than control and OVX heifers. These data suggest that the elevated levels of progesterone from the maintained corpora lutea and the subsequent absence of estrous activity in the hysterectomized heifers are advantageous for promoting growth in feedlot heifers. PMID- 4039308 TI - Genetic, phenotypic and environmental relationships between sow body weight and sow productivity traits. AB - Yorkshire and Duroc litter records were used to estimate genetic, phenotypic and environmental relationships between sow body weight and sow productivity traits. Two data sets with two subsets each were used to complete this study; 663 and 460 records included litter traits only, while 522 and 359 records also contained sow body weight for Yorkshires and Durocs, respectively. Heritability estimates for number born (NB), number born alive (NBA), total birth weight of live pigs (BWLIT), litter weight at 3 wk (WT3WK), sow weight at parturition (WTDAMPAR) and sow weight at weaning (WTDAMWN) were .24 +/- .14, .21 +/- .14, .42 +/- .16, .19 +/- .14, .72 +/- .21 and .42 +/- .18, respectively, for Yorkshires and .05 +/- .10, .04 +/- .10, .21 +/- .14, .25 +/- .15, .85 +/- .25 and .87 +/- .26, respectively, for the Durocs. Repeatability estimates for NB, NBA, BWLIT, WT3WK, WTDAMPAR and WTDAMWN were .13 +/- .06, .17 +/- .06, .27 +/- .06, .13 +/- .06, .64 +/- .05 and .54 +/- .05, respectively, for Yorkshires and .17 +/- .06, .21 +/- .06, .14 +/- .06, .17 +/- .06, .28 +/- .07 and .39 +/- .07, respectively, for Durocs. Genetic correlations among litter traits were high and positive in the Yorkshire data. Genetic correlations between NBA and WTDAMPAR, NBA and WTDAMWN, WT3WK and WTDAMPAR, and WT3WK and WTDAMWN were .37 +/- .25, .18 +/- .34, .60 +/- .29 and .29 +/- .45, respectively, in the Yorkshire data. Genetic correlations among litter traits in the Duroc analysis had large standard errors but were generally similar to the estimates obtained from the Yorkshire data. The genetic correlation between WTDAMPAR and WTDAMWN was .93 +/- .09 for Yorkshire sows. The primary conclusion from this study is that as selection increases sow productivity traits, there will be a positive correlated response in sow body weight. PMID- 4039309 TI - Effect of ovarian follicles on luteal regression in heifers. AB - Our objectives were to determine whether or not ovarian follicles contribute to spontaneous luteal regression in heifers and, if so, when during diestrus do follicles exert their effect. Thirty-one Holstein heifers having displayed at least one estrous cycle (19 to 21 d) were assigned, as available, to randomized blocks for a factorial experiment. Reproductive organs were exposed through a midventral incision on d 9, 12 or 15 postestrus (estrus = d 0). Visible follicles were electrocauterized and both ovaries were x-irradiated (1,500 rads) in treated heifers, whereas ovaries of controls were exteriorized but follicles were not destroyed and ovaries were not x-irradiated. In two additional heifers, the ovary containing the corpus luteum was exteriorized and x-irradiated on d 15 postestrus, but follicles were not electrocauterized. Jugular blood was collected before and every 8 h after surgery until d 24 postestrus. All heifers were ovariectomized on d 24 postestrus to inventory follicles and to weigh corpora lutea. No follicles (greater than or equal to 1 mm diameter) were observed in ovaries from treated animals and concentrations of estradiol-17 beta did not change over time, whereas different numbers of follicles were observed in ovaries from controls and concentrations of estradiol-17 beta increased (P less than .05) during proestrus. Hence, treatment destroyed follicles and prevented follicular development. On d 24 postestrus, corpora lutea from treated heifers (5.5 +/- .5 g) were heavier (P less than .001) than corpora lutea from controls (1.1 +/- .1 g), independent of day when follicles were destroyed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4039310 TI - Inhibition of bovine luteal function by indomethacin. AB - Experiments were conducted to determine the effects of infusing indomethacin, a prostaglandin synthetase inhibitor, into the uterine lumen on the development and function of the bovine corpus luteum in the presence and absence of concurrently administered oxytocin. Each treatment was given twice daily on d 4, 5 and 6 of the estrous cycle. Treatments (six heifers/group) and resulting estrous cycle lengths were as follows: (1) untreated controls, 20.6 +/- .4 d; (2) .2 M phosphate buffer vehicle infused into the uterine lumen, 21.0 +/- .6 d; (3) 40 mg indomethacin infused into the body of the uterus, 16.5 +/- 1.0 d; (4) 150 USP units oxytocin injected sc, 10.0 +/- 1.2 d and (5) a combination of oxytocin and indomethacin as in treatments 3 and 4, 14.1 +/- 1.3 d. Plasma concentrations of progesterone were lower (P less than .05) in each treatment group from d 7 onward, when compared with untreated and vehicle-treated controls. Indomethacin alone effectively inhibited the development and function of the corpus luteum, and was without effect on oxytocin-induced inhibition of luteal function. In summary, it appears that a prostaglandin of either uterine or ovarian origin, or both, is required for the normal development and function of the bovine corpus luteum. PMID- 4039311 TI - Comparisons of specific crosses from Duroc, Hampshire and Spot backcross sows. AB - One hundred 3/4 Duroc-1/4 Landrace (DDL), 3/4 Hampshire-1/4 Landrace (HHL) and 3/4 Spot-1/4 Landrace (SSL) backcross sows were randomly mated to Yorkshire boars to produce a total of 299 litters and 3,271 pigs to determine the effect of dam breeding on preweaning and postweaning performance of the pigs and litters. Litter sizes born and born alive were not significantly different among the three dam breeds studied. However, litter sizes alive at 21 d out of HHL sows were significantly larger than litter sizes out of SSL sows, while the litter sizes out of DDL sows were intermediate to the other two dam breeds. The DDL sows had significantly heavier litters at birth than did SSL sows, but the dam breeds did not differ in the weights of their litters at 21 and 42 d. Pigs out of DDL sows were heaviest at birth but weighed the least at 21 d, while pigs out of SSL sows were heaviest at 21 and 42 d of age. Pigs out of HHL sows weighed the least at birth and at 42 d. There were no significant differences among the dam breeds in the survival rate of their pigs. In the postweaning period, pigs out of HHL sows were the slowest growing and took the most days to reach 100 kg. Feed conversion and average daily feed consumption did not differ significantly among the three dam breeds studied. PMID- 4039312 TI - Effect of dietary crude protein level on the reproductive performance and growth of New Zealand white rabbits. AB - An experiment utilizing 391 preweaning and 187 postweaning litter records from 145 does was conducted for 12 mo to determine the effect of dietary crude protein level on performance of commercial New Zealand White rabbits. Does and their litters were fed alfalfa-based pelleted diets containing either 17.5, 19 or 20.5% crude protein (CP). In a separate experiment, the 17.5 and 20.5% CP diets were fed during lactation to 10 does to determine nitrogen (N) digestibility and retention. Body weights of does fed 17.5% CP were lower (P less than .01) than for the other treatments after 21 and 28 d of lactation. No differences (P greater than .10) were observed for doe weight at kindling, percentage fertility, litter size, preweaning litter mortality, 1- to 21-d consumption, preweaning feed efficiency and 28- to 56-d average daily consumption, average daily gain and average weight. Total born tended to be higher (P = .07) on higher protein levels but percentage born alive was greatest (P less than .01) on the 17.5% CP diet. Does fed 19% CP tended to have a greater number of parities (P = .06). Other significant differences observed for preweaning litter traits were between 17.5 and 19% CP groups. Does fed 19% CP had heavier litters at birth (P less than .01), at 21 d (P = .05) and 28 d (P = .06) and had greater 1- to 21-d litter gains and 21- to 28-d consumption (P = .05) than those fed 17.5% CP. For postweaning performance, feed efficiency values were lowest and mortality was highest for litters fed 20.5% CP. When litters were switched to different diets after weaning, mortality tended to be higher (P = .07) for animals that were fed 20.5% CP before weaning. The month of experiment effect did not influence any of the characters studied (P greater than .05). Parity number was important for percentage fertility, percentage born alive, litter birth weight and doe weight at 21 and 28 d (P less than .05). Does at first parity showed the poorest performance for all traits (except percentage fertility). Fertility fluctuated throughout the first four parities and then steadily declined. Does fed 20.5% CP had greater apparent dry matter and acid detergent fiber digestibilities and N intakes (P less than .05) and retained 90% more N during lactation (P = .22) than does fed 17.5% CP. Milk production and CP digestibility did not differ between the two diets tested.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 4039313 TI - Regression of induced corpora lutea by human chorionic gonadotropin in prepuberal gilts. AB - The effect of daily injections of human chorionic gonadotropin (HCG) on luteal maintenance in hysterectomized prepuberal gilts induced to ovulate and in hysterectomized mature gilts was studied. Twenty-four pre-puberal gilts, 120 to 130 d of age, were induced to ovulate with 1,000 IU pregnant mare serum gonadotropin followed 72 h later with 500 IU HCG. Nine of the 24 prepuberal gilts (bred controls) were artificially inseminated on d 0 (d 0 = d after HCG). Mature gilts that had displayed one or more estrous cycles of 17 to 22 d were used (d 0 = onset of estrus). All gilts, except the bred controls, were totally hysterectomized on d 6 to 9 and their corpora lutea (CL) marked with charcoal. From d 10 through 29, eight prepuberal and 10 mature hysterectomized gilts received daily injections of 500 IU HCG in saline while seven prepuberal and eight mature hysterectomized gilts received daily injections of saline vehicle. Jugular blood samples were quantitated by radioimmunoassay for estrogen and 13,14 dihydro-15-keto prostaglandin F2 alpha (PGFM), a metabolite of prostaglandin F2 alpha. One bred control gilt was pregnant on d 30, indicating that the prepuberal gilts used in the experiment were prepuberal. All mature gilts and six of seven prepuberal gilts that received saline had maintained CL to d 30. Eight of 10 mature gilts that received HCG had maintained CL to d 30, while only two of eight (P less than .05) prepuberal gilts that received HCG maintained CL to d 30. All gilts receiving HCG had numerous follicles and accessory luteal structures.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4039314 TI - Relationships among dietary lipid intake, serum cholesterol and ovarian function in Holstein heifers. AB - Experiments were performed to determine whether serum concentrations of total cholesterol (TC) undergo cyclic changes during the estrous cycle of dairy heifers and to assess the relationship between serum concentrations of TC and ovarian steroid hormones. The effects of a hypercholesterolemic diet upon luteal progesterone secretion also were determined. Experiment 1 involved five dairy heifers exhibiting normal estrous cycles. Serum concentrations of TC, progesterone, testosterone and estradiol-17 beta were determined in blood samples collected throughout a complete estrous cycle. A transient decline in TC was observed during the luteal phase of all heifers beginning on d 2 and reached a nadir 6 d after estrus. Highest mean concentrations of TC occurred between d -2 and +2 (96.3 +/- 8.2 mg/dl), which were markedly higher (P less than .05) than the lowest mean concentrations (76.3 +/- 10.3 mg/dl) observed on d 6. Concentrations of serum TC were negatively correlated (r = -.40; P less than .01) with progesterone between d 2 and 9. Serum TC was not correlated with testosterone or estradiol-17 beta. In Exp. 2, seven cycling Holstein heifers were fed a control diet for 70 d (Stage I), a diet containing 15% whole sunflower seed as a source of supplemental dietary lipid for 70 d (Stage II) and then the control diet for 70 d (Stage III). Diets were isocaloric and isonitrogenous. All heifers were synchronized with prostaglandin F2 alpha after wk 5 in each of the three feeding stages.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4039315 TI - Nitrogen utilization and ruminal fermentation in steers fed soybean meal treated with formaldehyde. AB - Four rumen-fistulated steers averaging 400 kg in body weight were used in a 4 X 4 Latin square arrangement with 18-d periods to investigate the effect of treating soybean meal (SBM) with formaldehyde on nitrogen (N) utilization and ruminal fermentation. Experimental diets, on a dry matter basis, consisted of 42% corn silage, 48.5% cracked corn-mineral mixture and 9.5% SBM treated with 0, .3, .6 or .9% formaldehyde by weight. Dry matter and organic matter digestibilities were not affected by treatment. Formaldehyde treatment of SBM resulted in a linear decrease in N digestibility (P less than .005) and urinary N excretion (P less than .01) and a quadratic increase (P less than .05) in N retention. The depression in apparent N digestibility was small when SBM was treated with .3% formaldehyde. This level of formaldehyde treatment also had little effect on in vitro enzymatic hydrolysis of SBM. Ruminal ammonia-N concentrations were lower (P less than .05) in steers fed formaldehyde-treated SBM. Ruminal pH was lower (P less than .05) at 6 and 8 h postfeeding while volatile fatty acid concentrations were higher (P less than .05) at 8 and 12 h postfeeding for steers fed untreated SBM. Propionic acid (mol/100 mol) decreased linearly (P less than .05) with increasing level of formaldehyde treatment. Urea-N concentrations in plasma were decreased (P less than .001) and plasma-free essential amino acid concentrations were increased (P less than .10) by formaldehyde treatment. Ruminal disappearance of N from polyester bags containing the SBM supplements was greatly reduced (P less than .005) by formaldehyde treatment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4039316 TI - Rapid kinetics of the glucose transporter from human erythrocytes. Detection and measurement of a half-turnover of the purified transporter. AB - The stopped flow method combined with fluorescence detection has been employed to study the rapid kinetics of the glucose transporter from human erythrocytes. Upon mixing the purified transporter reconstituted into unsealed membranes of erythrocyte lipids with 4,6-ethylidene D-glucose, a derivative that binds preferentially to the substrate site on the outer domain of the transporter, there was a rapid, first-order decrease in the intrinsic fluorescence of the protein. Three properties of this transient indicate that it represents a half turnover of the transporter from a conformation with the substrate site facing inward to one with this site facing outward. The first-order rate constant decreased as the concentration of ethylidene glucose was increased; the value of the rate constant for the process is similar to that expected from steady-state kinetic studies of transport in the erythrocyte; and D-glucose at low concentration increased the rate of reaction. This study is the first determination of the kinetics of a half-turnover for a transport system of the facilitated diffusion type. The identification of this step provides direct evidence for the alternating conformation mechanism of transport. PMID- 4039317 TI - Influence of retinoid nutritional status on cellular retinol- and cellular retinoic acid-binding protein concentrations in various rat tissues. AB - Studies were conducted to explore the effects of differences in retinoid nutritional status and of sex on the tissue distribution and levels of cellular retinol-binding protein (CRBP) and of cellular retinoic acid-binding protein (CRABP) in the rat. Sensitive and specific radioimmunoassays were developed and employed to measure the levels of both CRBP and CRABP. Four groups of six male rats each were fed experimental diets that differed greatly in the amount and kind of retinoids provided, but were otherwise identical. These groups were comprised of rats that were normal controls, retinoid-deficient, retinoic acid fed, and excess retinol-fed. A fifth group of six female rats was fed the control diet. Immunogens identical with rat testis CRBP and CRABP, as assessed by radioimmunoassay displacement curves, were found in every rat tissue examined (21 tissues in males, 18 in females). The highest levels of CRBP were found in the proximal portion of the epididymis, the liver, and kidney. The highest levels of CRABP were found in the seminal vesicles, vas deferens, and skin. A significant (p less than 0.01) inverse relationship was found between CRBP and CRABP levels in the different tissues of the male reproductive tract. In both males and females, CRBP levels were highest in the gonads and proximal portion of the reproductive tract and decreased distally, whereas the opposite was true for CRABP. Retinoid-deficient rats showed reduced tissue levels of CRBP; thus, tissue CRBP levels are influenced by diet and retinoid availability. No differences in tissue CRBP levels were found in the rats fed the control, the retinoic acid, or the excess retinol diets. Female control rats had higher CRBP levels than male controls in 4 of 15 tissues compared (liver, lung, thymus, and fat). In contrast, tissue CRABP levels showed no diet- or sex-dependent differences. Only in one tissue, the skin, were differences observed (lower CRABP in retinoid-deficient and in female rats). Thus, CRABP metabolism and levels appear to be minimally influenced by the amount or kind of retinoid ligand available or by sex. PMID- 4039318 TI - Molecular properties of bovine interphotoreceptor retinol-binding protein. AB - Interphotoreceptor retinol-binding protein (IRBP) is a large retinol-carrying glycoprotein, located only in the interphotoreceptor (or subretinal) space of vertebrate eyes. It has recently been purified to apparent homogeneity. The present report presents its sedimentation, spectroscopic, and binding properties. The molecular weight of bovine IRBP, determined by sedimentation equilibrium, is 133,000. The sedimentation coefficient is 5.8S. The Stokes radius, 56 A, obtained from gel-filtration chromatography, is much larger than that expected for a globular protein of the same molecular weight. These results indicate that IRBP is asymmetric (it can modeled as a prolate ellipsoid of revolution with axial ratio of about 8:1) and explain the overestimates of molecular weight obtained in previous studies based on size-exclusion methods. The molar absorption coefficients for IRBP (at 280 nm) and for bound retinol are both unaffected by ligand dissociation. Fluorescence of the holoprotein displays neither fine structure nor energy transfer from tryptophan to bound retinol. Circular dichroism suggests a secondary structure containing approximately 15% alpha-helix and approximately 20% beta-structure, unchanged by the presence of ligand. The binding of retinol creates a positive, extrinsic Cotton effect at 330 nm, proportional to the amount of retinol bound. The apparent dissociation constant for all-trans-retinol is 1.3 X 10(-6) M. This relatively loose binding implies that, if required during the visual cycle, IRBP should be able to transfer its ligand to other binding proteins in the neural retina and retinal pigment epithelium. PMID- 4039319 TI - Spontaneous fibrinolysis in whole human plasma. Identification of tissue activator-related protein as the major plasminogen activator causing spontaneous activity in vitro. AB - Spontaneous fibrinolysis of plasma clots was studied by following the lysis of the clots formed in 125I-fibrinogen-supplemented citrated plasma. Lysis of the clots invariably follows sigmoidal kinetics with S50 (the time required for 50% clot lysis) ranging from 3.5 to 4.7 days in 8 samples of pooled blood bank plasma and in the majority of apparently healthy donor plasmas. The spontaneous lysis of factor XII-deficient and prekallikrein-deficient plasmas was found to be similar to that of normal plasma. Addition of ellagic acid or antibodies against kallikrein or urokinase to normal pooled plasma did not alter significantly its rate of spontaneous lysis. On the other hand the addition of antibody against tissue activator (t-PA) inhibited over 80% of the spontaneous fibrinolysis in a 7 day incubation period at 37 degrees C, and the clot visually persisted for more than a month. Therefore, the factor XII-dependent components and prourokinase/urokinase system do not contribute significantly in whole plasma fibrinolysis in vitro, while the t-PA-related protein appears to be the major plasminogen activator responsible for initiating spontaneous fibrinolysis in whole plasma. Exogenous addition of increasing amounts of purified HeLa cell t-PA to normal pooled plasma in the ng/ml range cause progressively faster clot lysis. By extrapolation, normal pooled plasma is found to contain endogenous tissue activator in an amount functionally equivalent to 2 ng/ml of purified 60-kDa t PA. The molecular nature of the t-PA-related proteins in plasma was studied by zymographic and immunological methods. The major t-PA-related protein in plasma was found to have a molecular mass of 100 kDa as determined by zymography. By incubating purified HeLa 60-kDa t-PA with a t-PA-depleted plasma, the 100-kDa component can be generated in plasma, suggesting that the latter is formed as a result of the binding of 60-kDa t-PA to a binding protein in plasma. PMID- 4039320 TI - Inhibition of the activation and catalytic activity of insulin receptor kinase by zinc and other divalent metal ions. AB - The autophosphorylation reaction responsible for conversion of insulin receptor (from human placenta) to an active tyrosyl-protein kinase was shown to be inhibited by Zn2+ and other divalent metal ions. The order of inhibitory potency was found to be Cu2+ greater than Zn2+, Cd2+ greater than Co2+, Ni2+. Autophosphorylation of insulin receptor was almost completely blocked by 10 microM Zn2+. Zn2+, however, did not appear to affect the binding of insulin to its receptor. Histidine, a chelator of Zn2+, protected against the inhibitory effects of Zn2+. The failure of histidine to regenerate the competence of the Zn2+-inhibited receptor to undergo autophosphorylation suggested that the inhibition by Zn2+ was irreversible. In addition to inhibiting autophosphorylation, Zn2+ inhibited the tyrosyl-protein kinase activity of highly purified phosphorylated receptor. Zn2+ was also observed to inhibit phosphotyrosyl-protein phosphatase activity present in preparations of partially purified insulin receptor. These inhibitory effects of Zn2+ should be considered in the design of protocols for the isolation and handling of insulin receptor and possibly other tyrosine kinases. Additionally, the possible physiological significance of the inhibition of insulin receptor kinase by Zn2+ is discussed in light of the fact that Zn2+ is accumulated in and secreted from pancreatic islet cells together with insulin. PMID- 4039321 TI - Hematin-catalyzed epoxidation of 7,8-dihydroxy-7,8-dihydrobenzo[a]pyrene by polyunsaturated fatty acid hydroperoxides. AB - Hematin catalyzes the epoxidation of 7,8-dihydroxy-7,8-dihydrobenzo[a]pyrene (BP 7,8-diol) by 13-hydroperoxy-9-cis,11-trans-octadecadienoic acid and other fatty acid hydroperoxides in the presence of detergent. The major oxidation product is the anti-dihydrodiolepoxide and the minor product is the syn-dihydrodiolepoxide. (+)-BP-7,8-diol is oxidized to (-)-anti-diolepoxide and (+)-syn-diolepoxide whereas (-)-BP-7,8-diol is oxidized to (+)-anti-diolepoxide and (-)-syn diolepoxide. Oxygen labeling studies indicate that the source of the epoxide oxygen is O2. The phenolic antioxidants butylated hydroxyanisole and butylated hydroxytoluene inhibit epoxidation by 100 and 93%, respectively. These observations suggest that hematin-catalyzed epoxidation proceeds by a free radical mechanism. Incubation of hematin, BP-7,8-diol, and a series of fatty acid hydroperoxides containing two, one, or zero double bonds alpha to the carbon bearing the hydroperoxide indicates that at least one double bond is essential for generation of the epoxidizing agent. Taken with results of the study of the metabolism of 13-hydroperoxy-9-cis,11-trans-octadecadienoic acid by hematin described in the accompanying paper (Dix, T. A., and Marnett, L. J. (1985) J. Biol. Chem. 260, 5351-5357), these results indicate that the epoxidizing agent is a peroxyl radical generated by coupling of O2 to a carbon-centered radical derived from the double bonds adjacent to the hydroperoxide group. The detergents Tween 20, Triton X-100, and Triton X-405 dramatically enhance epoxidation above but not below their critical micellar concentrations. The intensity and lambda max of the ultraviolet absorption spectrum of BP-7,8-diol increase in the presence of detergent, indicating that an important role of detergent is solubilization of the hydrophobic substrate. However, detergent also stimulates the hematin-catalyzed oxidation of a water-soluble polycyclic hydrocarbon, bis (carboxyethyl)-anthracene, suggesting that detergent has an effect on the peroxidase activity of hematin. A detailed mechanism for epoxidation of BP-7,8 diol by hematin and fatty acid hydroperoxides is presented and its relevance to other hydroperoxide-dependent epoxidizing systems is discussed. PMID- 4039322 TI - Post-translational import of fatty acyl-CoA oxidase and catalase into peroxisomes of rat liver in vitro. AB - Total polysomal RNA of rat liver was translated in vitro in a rabbit reticulocyte lysate system. The translation products were mixed with a postnuclear supernatant fraction of rat liver and incubated post-translationally at 26 degrees C for 15 60 min. The import assay mixture was separated into a particulate fraction and supernatant by centrifugation, both of which were analyzed by immunoprecipitation with a goat antibody against rat liver peroxisomal proteins, sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and fluorography. One peroxisomal translation product (Mr 72,000) appeared in the particulate fraction, was partly proteinase K-resistant, and addition of detergents prior to proteolysis abolished this resistance. In isopycnic centrifugation of the uptake assay mixture, the protease-resistant 35S-polypeptide of Mr 72,000 cosedimented with the peroxisomes. This translation product was identified immunochemically as fatty acyl-CoA oxidase; both before and after import it was indistinguishable in size from subunit A of the purified enzyme by prolonged sodium dodecyl sulfate polyacrylamide gel electrophoresis. When the cell-free translation products were incubated with highly purified peroxisomes, 35S-catalase entered peroxisomes (by the criterion of protease resistance), and its entry was stimulated by the addition of a high speed supernatant (cytosolic) fraction of rat liver. These results demonstrate the post-translational import into peroxisomes in vitro of at least two cell-free translation products. PMID- 4039323 TI - Structural relationships of the three stimulatory factors of RNA polymerase II from Ehrlich ascites tumor cells. AB - The structural relationships of S-II, S-II', and S-I(b) stimulatory proteins of RNA polymerase II purified from Ehrlich ascites tumor cells were investigated. From analysis of the amino acid compositions and tryptic peptide maps of these proteins labeled with radioiodinated Bolton-Hunter reagent, it was concluded that S-I(b) is a part of S-II located at either the amino- or carboxyl-terminal and that only this region mainly contains radioiodinatable amino acid residues when labeled using 125I. On chymotryptic digestion, S-II was cleaved to 21- and 18-kDa fragments in the presence of DNA. The 21-kDa fragment was found to be sufficient for stimulation of RNA polymerase II. It was suggested that S-II' is formed by phosphorylation of S-II in the domain containing the 18-kDa fragment. PMID- 4039324 TI - The standardization of an assay for pertussis toxin and antitoxin in microplate culture of Chinese hamster ovary cells. AB - A microplate assay, based on the clustering effect induced by pertussis toxin (PT) in Chinese hamster ovary (CHO) cells, has been developed and standardized. Toxin titration is done directly in the culture microplate by twofold dilutions of 25 microliters of test material to which are added 10 000 freshly trypsinized cells in 200 microliters of culture medium per well. The dilution causing the clustering effect is determined by direct microscopic observation after 48 h of incubation. The method allows detection of 50-100 pg toxin per millilitre. For determination of neutralizing antibodies (antitoxin), twofold dilutions of 25 microliters of antiserum are first made directly in the culture microplate. Thereafter 25 microliters of toxin, containing four times the minimal clustering concentration, is added to each well. After three hours for neutralization at +37 degrees C, cells are added, incubated and examined as above. The assay has been found to be simple and reproducible for measuring the antibody response to PT in human and different animal sera. For titration of bacteria associated toxin, the CHO cells are seeded and incubated for 24 h before the addition of bacteria. Incubation and examination are done as described for toxin titration. PMID- 4039325 TI - Compartmentalization of algal bioluminescence: autofluorescence of bioluminescent particles in the dinoflagellate Gonyaulax as studied with image-intensified video microscopy and flow cytometry. AB - Compartmentalization of specialized functions to discrete locales is a fundamental theme of eucaryotic organization in cells. We report here that bioluminescence of the dinoflagellate alga Gonyaulax originates in vivo from discrete subcellular loci that are intrinsically fluorescent. We demonstrate this localization by comparing the loci of fluorescence and bioluminescence as visualized by image-intensified video microscopy. These fluorescent particles appeared to be the same as the previously described in vitro "scintillons." We attribute the endogenous fluorescence to that of the bioluminescence substrate, luciferin, because (a) the fluorescence excitation and emission characteristics are comparable, (b) the autofluorescence is lost after exhaustive stimulation of bioluminescence, and (c) the fluorescence of discharged particles in vitro can be restored by adding luciferin. The fluorescence in vivo exhibits a standard property of circadian (daily) rhythmicity: under constant environmental conditions, the intensity of the particle fluorescence fluctuates cyclically (it is maximal during the night phase and is low during the day). Thus, luciferin is localized within the cell at discrete loci from which the bioluminescence emanates; the cellular quantity of luciferin is rhythmically modulated by the circadian clock. PMID- 4039326 TI - Are cross-bridging structures involved in the bundle formation of intermediate filaments and the decrease in locomotion that accompany cell aging? AB - Five different fibroblast strains derived from donors of a wide range of ages were used for investigation of senescence-associated changes in the organization of intermediate filaments (IFs) and the activity of cell locomotion. Results of immunofluorescence microscopy demonstrate that, in large and flat in vitro aged fibroblasts, vimentin-containing IFs are distributed as unusually organized large bundles. Electron microscopic examination shows that these large bundles are indeed composed of filaments of 8-10 nm. Such a profile of large bundles is rarely seen in young fibroblasts whose IFs are usually interdispersed among microtubules. Within the large filament bundles of senescent fibroblasts, cross bridge-like extensions are frequently observed along the individual IFs. Immunogold labeling with antibody to one of the cross-bridging proteins, p50, further illustrates the abundance of interfilament links within the IF bundles. The senescence-related increase in interfilament association was also supported by the results of co-precipitation between vimentin and an associated protein of 50,000 D. Time-lapse cinematographic studies of cell locomotion reveal that accompanying aging, fibroblasts have a significantly reduced ability to translocate across a solid substratum. These results led me to suggest that the increased interfilament links via cross-bridges may in part contribute to the mechanism that orchestrates the formation of large filament bundles. The presence of enormous bundles in the cytoplasm may physically impede the efficiency of locomotion for these nondividing cells. PMID- 4039327 TI - The cytoplasmic filament system in critical point-dried whole mounts and plastic embedded sections. AB - High voltage electron microscopy of intact cells prepared by the critical point drying (CPD) procedure has become an important tool in the study of three dimensional relationships between cytoplasmic organelles. It has been claimed that critical point-dried specimens reveal a structure that is not visible in sections of plastic-embedded material; it has also been claimed that this structure, in association with known cytoplasmic filaments, forms a meshwork of tapering threads ("microtrabecular lattice"). Alternatively, this structure might be a surface tension artifact produced during CPD. To test possible sources of artifacts during CPD, model fiber systems of known structure were used. It was found that traces of water or ethanol in the CO2 caused distortions and fusion of fibers in pure muscle actin, fibrin, collagen, chromatin, and microtubules that produce a structure very similar to the proposed "microtrabecular lattice." These structures were, however, well preserved if water and ethanol were totally excluded from the CO2. The same results were obtained with whole mounts of cultured cells. A "microtrabecular lattice" was obtained if some water or ethanol was present in the pressure chamber. On the other hand, when water or ethanol were totally excluded from the CO2 during CPD, cytoplasmic filaments were uniform in thickness similar to their appearance in sections of plastic-embedded cells. It is concluded that the "microtrabecular lattice" is a distorted image of the cytoplasmic filament network produced during CPD by traces of water or ethanol in the CO2. PMID- 4039329 TI - Slow posttranslational modification of a neurofilament protein. AB - The synthesis and subsequent modification of neurofilament (NF) polypeptides has been examined in pulse-chase experiments, using cultured chick spinal cord neurons. Fluorography of the [35S]methionine-labeled cytoskeletal proteins, after separation by two-dimensional gel electrophoresis, revealed that (a) the mid-size chicken NF protein, NF-M160, is synthesized as a smaller and more basic precursor, NF-M130; (b) beginning approximately 8 h after translation, NF-M130 slowly and continuously becomes larger and more acidic, attaining the size and charge of NF-M160 16 or more h later, and undergoing no further change in mobility for many days thereafter; and (c) in contrast, the low molecular weight NF protein, NF-L, is synthesized as such, and undergoes no subsequent change in apparent size or charge. Additional experiments provided evidence that the conversion of NF-M130 to NF-M160 is due, at least in part, to phosphorylation: (a) Incubation of similar cultures in 32PO4 resulted in incorporation into NF M160 and transitional forms, but not into NF-M130. (b) An antiserum to NF-M160 was found by immunoblot analysis to bind strongly to untreated NF-M160, but poorly to phosphatase-treated NF-M160, and not at all to NF-M130. It has already been demonstrated (Bennett, G. S., S. J. Tapscott, C. DiLullo, and H. Holtzer, 1984, Brain Res., 304:291-302) that this anti-NF-M160 fails to stain the soma of motor neurons in sections of chick spinal cord, but detects an increasing gradient of immunoreactivity in the proximal axons. These results, together with the known kinetics of axoplasmic transport of NF, suggest that the mid-size chicken NF protein is synthesized as NF-M130 and is extensively modified, at least in part by phosphorylation, to become NF-M160 during transport along proximal neurites. Once maximally modified, NF-M160 undergoes no further net change during transport along distal neurites. PMID- 4039328 TI - Endocytosis and degradation of interstitial retinol-binding protein: differential capabilities of cells that border the interphotoreceptor matrix. AB - Between the pigment epithelium and the outer limiting membrane of the retina is an extracellular compartment filled with the interphotoreceptor matrix (IPM). A prominent component of the IPM is a glycoprotein known as interstitial retinol binding protein (IRBP). Using in vitro techniques, we compared the ability of the cells that border this compartment to internalize colloidal gold (CG) coated with either IRBP or ovalbumin, a glycoprotein not found in the IPM. Neither IRBP-CG nor ovalbumin-CG was internalized by the Muller's cells. Both rod and cone photoreceptors take up IRBP-CG, which is observed in small vesicles and multivesicular bodies. Neither photoreceptor type takes up ovalbumin-CG. Acid phosphatase cytochemistry indicates that acid phosphatase reaction product in the multivesicular bodies co-localizes with IRBP-CG, which suggests that this molecule is degraded by rod and cone photoreceptors and is not recycled. The pigment epithelium internalizes IRBP-CG and ovalbumin-CG, both of which remain in small cytoplasmic vesicles near the apical plasma membrane. There is no indication that vesicles that contain either IRBP-CG or ovalbumin-CG fuse with the lysosomal system in the pigment epithelial cells during the incubation. PMID- 4039330 TI - Vasoactive amines modulate actin cables (stress fibers) and surface area in cultured bovine endothelium. AB - Cultured bovine aortic endothelial cells were fixed and stained with NBD phallicidin and quantitated with a digital image analyzer for changes in actin cables and surface area. Serotonin (5-HT), norepinephrine (NE), dopamine and histamine (all at 10(-4)M concentrations) were tested for their ability to induce cytoskeletal changes. Only 5-HT and NE increased actin cables significantly (p less than 0.01), 80.7% and 97.9%, respectively. Dopamine and histamine treated cells showed a 67.4% and 80.8% decrease in actin cables respectively (p less than 0.01). Stimulated increases of actin cables by 5-HT were inhibited by Ketanserin, and propranolol inhibited NE stimulation of actin cables. Treatment of cells with these blockers alone also decreased actin cables below control values (p less than 0.01). Pretreatment of cells with diphenhydramine, but not cimetidine, inhibited histamine-induced decreases in actin cables. Stimulation of surface area by 5-HT and NE was also observed, with 40.8% and 80.7% increases respectively, when compared with controls (p less than 0.01). The increases in actin cables were associated with a lack of ruffled edges that are indicative of motile cells. In contrast, induced decreases in actin cables resulted in cells with ruffled edges. Exogenous 5-HT and NE have been shown to prevent the increased permeability visible as extravasation of red blood cells from postcapillary venules in thrombocytopenic animals. The present data suggest that 5-HT and NE may be involved in maintaining the endothelial barrier function by a receptor-mediated stimulation of actin cables. Also, histamine-induced decreases in actin cables may be correlated with the amine's action in vivo as a mediator of increased inflammatory permeability. PMID- 4039331 TI - Liver tyrosine kinase activation during early stages of chemical hepatocarcinogenesis. AB - Protein phosphorylation at tyrosine residues is believed to be involved in several important cellular processes because tyrosine-specific protein kinase activation is associated with stimulation of cellular proliferation by hormones and growth factors, embryogenesis, and retroviral cell transformation. Because cell proliferation is thought to be an essential component of chemical carcinogenesis, liver tyrosine-specific protein kinase activity was examined during the early stages of the Solt and Farber chemical hepatocarcinogenesis model. Rats were given diethylnitrosamine in one dose (200 mg/kg, IP) followed by 2 weeks of dietary 0.02% 2-acetylamino-fluorene starting at day 14 after diethylnitrosamine, followed by partial hepatectomy on day 21. By day 32 this regimen produces a relatively synchronized population of hyperplastic liver nodules up to 1.5 mm in diameter. Rats were sacrificed on day 32, their livers were perfused with cold normal saline, homogenized, and centrifuged at 1,000g for 10 min. The resulting supernatant was centrifuged at 30,000g for 30 min and the pellet was assayed for tyrosine kinase activity using the synthetic peptide [Val5]angiotensin II as substrate. Rats that received the complete regimen had a 2.6-fold increase in their liver tyrosine kinase activity as compared to sham controls (2.4 pmoles/min/mg protein vs 6.4 pmoles/min/mg protein, P less than .05). In contrast, rats that received a partial regimen (ie, partial hepatectomy, or 2-acetylaminofluorene + partial hepatectomy, or diethylnitrosamine + 2 acetylaminofluorene) did not have elevated tyrosine kinase activity nor did they have hyperplastic nodules. These preliminary data suggest that activation of liver tyrosine kinase is associated with the very early stages of chemical hepatocarcinogenesis. PMID- 4039332 TI - Solubilization, reconstitution, and attempted affinity chromatography of the sugar transporter of the erythrocyte membrane. AB - Reconstitution of the sugar transport system of human erythrocytes into artificial liposomes was achieved by freezing, thawing, and sonicating preformed phospholipid vesicles in the presence of intact ghosts, protein-depleted ghosts, or detergent-treated ghosts. D-glucose equilibrium exchange activities and affinity constants in the range of the reported erythrocyte values were reached in the best experiments. Whereas the extraction of peripheral membrane proteins did not depress the transport function crucially after reconstituting these protein-depleted ghosts, the selective solubilization of integral membrane proteins by a variety of nonionic detergents resulted in an uncontrollable, continuously increasing inactivation of the carrier. However, Emulphogene BC-720 extracts could be prepared in which the glucose transporter retained activity for days at 4 degrees C. These extracts were applied to affinity chromatography matrices of phloretin-Agarose, prepared by coupling phloretinyl-3'-benzylamine (PBA) to CH-Sepharose 4B and to Affigel 202. Although the solubilized sugar transporter appeared to be selectively adsorbed to both PBA matrices, it could not be eluted by specific counter ligands or gentle eluants in a biologically active form. However, chaotropic agents could be used to elute intrinsic proteins, including bands 3 and 4.5, from the Affigel affinity medium. PMID- 4039333 TI - Determination of demecarium bromide and related compounds by high-performance liquid chromatography. AB - A high-performance liquid chromatographic method for the determination of demecarium bromide and related process intermediate and companion products is described. The compounds of interest are separated by isocratic reversed-phase chromatography on a mu Bondapak CN column using UV detection. The reproducibility of the method and stability of demecarium bromide is demonstrated. Applications presented for the method include quantitation of demecarium bromide in aqueous solutions and control of the raw material. PMID- 4039334 TI - Improved high-performance liquid chromatography of sphingomyelin. PMID- 4039336 TI - Pemphigus vulgaris in only one of two monozygotic twins. PMID- 4039337 TI - Effects of intermittent electrical shock on responses related to milk ejection. AB - Electrical shock is perceived to be a problem on many dairy farms. Thirteen cows were subjected to intermittent electrical shock (5 s on, 25 s off) at a.m. and p.m. milkings for 7 days. Seven cows were subjected to 3.6 mA shocks starting with preparation (1 min udder wash and dry) and six cows to 6.0 mA. One additional cow initially in the 6.0 mA group had to be removed from the study because of severe behavioral responses to shock. Compared to 5-day preshock and postshock periods, milk yield, milking time, and Wisconsin Mastitis Test scores were not affected by shock. Maximum rate of milk flow increased slightly. The number of behavioral events such as lifting legs during milking increased with a greater increase in the 6.0 mA group. Heart rate was elevated (+3 beats/min) only in response to shock during preparation (initial shock). For selected days, time to peak oxytocin response was delayed in the 3.6 mA group, and peak prolactin and area under prolactin response curves increased similarly for both groups during shock. There were significant a.m.-p.m. differences in milk yield, milking time, maximum rate of milk flow, heart rate, and responses of oxytocin and prolactin. We think that milk yield can be maintained, at least in the short term, in cows subjected to electrical shock due to power-line problems if dairy producers take exceptional care to accommodate behavioral responses. PMID- 4039335 TI - Platelet antibodies of the IgM class in immune thrombocytopenic purpura. AB - The clinical course and response to therapy of patients with immune thrombocytopenic purpura (ITP) are not completely determined by the level of IgG present on the platelet surface. It is possible that antibodies of other immunoglobulin classes also play a role in platelet destruction in some of these patients. Therefore, we studied 175 patients with ITP for the presence of IgM anti-platelet antibodies using radiolabeled polyclonal or monoclonal anti-IgM. We observed that 57% of patients with clinical ITP had increased levels of IgM on their platelets, compared with normal controls and patients with thrombocytopenia who did not have ITP (less than 10%), (P less than 0.01). We obtained similar results using either radiolabeled polyclonal or monoclonal anti-IgM, reagents whose integrity was first characterized using erythrocytes coated with defined amounts of IgM antibody. Among patients with increased platelet-IgM there was a significant correlation both with the presence of increased platelet-C3 as well as the amount of platelet-C3 (P less than 0.01, r = 0.53). We demonstrated the presence of warm-reacting IgM anti-platelet antibodies in the plasma of two of these patients who were further studied. The isolated IgM fraction from these two plasmas was able to activate complement and place 3H-C3 on normal platelets. These studies demonstrate the presence of warm-reacting IgM anti-platelet antibodies in some patients with ITP. They suggest that the binding of complement to platelets by IgM antibodies may initiate platelet clearance as well as enhance the effect of IgG antibodies in ITP. PMID- 4039338 TI - Environmental pathogens and intramammary infection during the dry period. AB - Rate of coliform and streptococcal intramammary infection during the dry period was studied in 168 dry periods. Coliform infection rate was influenced by stage of dry period, parity, and season during which dry periods occurred. Effects of dry cow therapy, immunization, or induced inflammation on coliform infection rate were minimal. Coliform infections originating in the first 50% of the dry period and persisting to lactation were predominantly other than Escherichia coli, whereas the majority originating in the last 50% of the dry period and persisting to lactation were Escherichia coli. Duration of streptococcal infections was greater than coliform infections. Dry cow therapy reduced streptococcal infection rate, and the effect was exerted primarily during the first 25% of the dry period. Effects of parity and season were not significant and likely masked by the positive effects of dry cow therapy. Results support the contention that all quarters of all cows should be dry treated for maximum reduction of new streptococcal infection during the dry period. Results suggest that methods other than conventional dry cow therapy are required for control of coliform infection during the dry period and streptococcal infection during the latter half of the dry period. PMID- 4039339 TI - Methionine deficiency in early-weaned dairy calves fed pelleted rations based on corn and alfalfa or corn and soybean proteins. AB - Holstein bull calves weaned at 4 wk of age were assigned to one of three replicated 4 X 4 Latin squares at 5 to 6 wk. Trials were abomasal infusion of 0, .30, .60, and either 90 (Trials 2 and 3) or 1.20 g (Trial 1) L-methionine/kg pelleted starter ration consumed. In Trials 1 and 2, ration ingredients of the ration contributed the following percentages of total crude protein: corn meal 39, alfalfa meal 48, and soybean meal 12; dry matter of rations contained 13.6 and 13.9% crude protein and .26 and .32% sulfur. Infusion of .60 g methionine in Trial 1 tended to depress excretion of nitrogen in urine and increase nitrogen retention. In Trial 2, urine nitrogen excretion and retained nitrogen responded in a quadratic fashion; infusion of .30 and .60, and either .90 (Trials 2 and 3) or 1.20 g (Trial 1) L-methionine/kg pelleted starter ration consumed. In Trials 1 and 2, ingredients of the ration contributed the following percentages of total crude protein: corn meal 39, alfalfa meal 48, and soybean meal 12; dry matter of rations contained 13.6 and 13.9% crude protein and .26 and .32% sulfur. Infusion of .60 g methionine in cretion 9%. Relationship between plasma methionine and infused methionine was linear for all trials. Methionine is the first limiting amino acid for early-weaned calves fed complete pelleted rations based on corn and either alfalfa or soybean proteins. PMID- 4039340 TI - Uterine contractions and fertility following clitoral massage of dairy cattle in estrus. AB - Lactating and nonlactating Holstein cows received 30 s of gentle clitoral massage to determine its effect on uterine contractility and oxytocin concentrations in blood. Clitoral stimulation caused an immediate single uterine contraction, and this could be repeated at 2.5-min intervals. Oxytocin concentrations did not change during intensive blood sampling following clitoral massage. Thus, the uterine response is interpreted as neurally mediated. Eighteen full-time inseminators were allotted to two groups, balanced so that each day half were inseminating control and half treated animals (5 s of clitoral massage following insemination). The 56-day nonreturns for 2090 controls were 74.3% versus 74.0% for 2049 animals receiving clitoral massage. Heifers were more fertile than cows (81.9% versus 70.6% nonreturns), but there was no indication that clitoral massage altered the nonreturn rate in either age group. Also, the time of day animals were inseminated did not affect nonreturn rate. PMID- 4039341 TI - [Photoactivation of the catalytic properties of a melanin pigment of fungal origin]. PMID- 4039342 TI - The acute effects of prostaglandin E1 on the pulmonary circulation and oxygen delivery in patients with the adult respiratory distress syndrome. AB - Prostaglandin E1 was administered intravenously to 10 patients who had the adult respiratory distress syndrome associated with severe infection in order to investigate its hemodynamic effects. Infusion of PGE1 significantly decreased the mean pulmonary arterial pressure, mean systemic arterial pressure, pulmonary vascular resistance and systemic vascular resistance, and increased the cardiac index, oxygen delivery and oxygen consumption. No significant difference was noted in the intrapulmonary shunt fraction. These results indicate that administration of PGE1 improves pulmonary hemodynamics and tissue oxygenation in patients with acute respiratory distress syndrome, by reducing right ventricular afterload and increasing the cardiac index. PMID- 4039343 TI - Relation of left ventricular function and prognosis in hypertrophic cardiomyopathy: an angiographic study. AB - Left ventricular cineangiograms performed at the time of diagnosis in 88 patients with hypertrophic cardiomyopathy were digitized to evaluate the relation of left ventricular function and prognosis in hypertrophic cardiomyopathy. Eleven patients died suddenly after a mean follow-up period of 7.5 +/- 7 years, 10 patients died of congestive heart failure or after cardiac surgery and 67 were alive after a mean follow-up period of 8.6 +/- 4 years. Measurements of left ventricular volume, ejection fraction, peak rate of ejection and filling and time to peak rate of ejection and filling were derived from curves of ventricular volume and its rate of change during the cardiac cycle. Patients who died suddenly had a lower peak rate of ventricular ejection (stroke volume-normalized peak ejection rate 5.41 +/- 0.69 versus 6.24 +/- 1.33 s-1; p = 0.006) and lower peak rate of ventricular filling (end-diastolic volume-normalized peak filling rate 4.02 +/- 0.94 versus 4.88 +/- 1.53 s-1; p = 0.02) and stroke volume normalized peak filling rate (4.75 +/- 1.08 versus 5.82 +/- 1.70 s-1; p = 0.01) compared with survivors. Stepwise regression analysis revealed that sudden death was best predicted by the combination of increased end-diastolic volume, small end-systolic volume and low peak filling rate (predictive accuracy 32%, false negative 18% and false positive 28%). The addition of clinical features and hemodynamic measurements to the analysis improved predictive accuracy to 43% (false negative 18% and false positive 18%). Ambulatory electrocardiographic monitoring performed in 57 of the 88 patients 1 month to 17 years (median 8 years) after diagnosis revealed ventricular tachycardia in 14 (25%). Of these, 10 who survived had hyperkinetic systolic function at diagnosis, whereas the 4 who died suddenly had impaired systolic function (end-diastolic volume-normalized peak ejection rate 5.93 +/- 1.2 versus 4.01 +/- 1.2 s-1, respectively; p = 0.04). In hypertrophic cardiomyopathy, ventricular tachycardia is a sensitive but nonspecific marker of adults who are at risk of sudden death. Impaired systolic function may be an important determinant of which patients with ventricular tachycardia die suddenly. This study shows that indexes of ventricular function contribute to the identification of patients at particular risk of sudden death. However, the predictive power of the clinical features and hemodynamic and angiographic measurements that could be assessed was poor.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 4039344 TI - Asymptomatic bronchial hyperresponsiveness in rhinitis. AB - Methacholine inhalation tests are used to help in the diagnosis of asthma when spirometry is normal. However, the significance of increased methacholine responsiveness in patients with rhinitis and no symptoms of asthma is not known. One possibility is that it is a false positive result; another possibility is that it indicates subclinical asthma. We investigated these possibilities in 25 patients with rhinitis, whose attending physician had not made a diagnosis of asthma, by comparing responsiveness to methacholine expressed as the provocation concentration to cause a fall in FEV1 of 20% (PC20) with responsiveness to the natural stimulus of isocapnic hyperventilation of cold air and the diurnal variation of peak flow rate. Asthma was recognized objectively by variable airflow obstruction documented by one of the latter two tests. The PC20 ranged between 4 and greater than 64 mg/ml. In 10 patients the PC20 was less than 16 mg/ml. Five of these patients had bronchoconstriction in response to hyperventilation, and a further two patients demonstrated increased variability of peak flow rates. Thus, in seven of 10 patients, increased bronchial responsiveness was confirmed by the use of two different methods, although they were asymptomatic, and the increased response to methacholine was not a false positive result. In the remaining three patients the PC20 was borderline increased (8 to 16 mg/ml). The results indicate that methacholine responsiveness in the asthmatic range in patients with rhinitis is associated with variable airflow obstruction and subclinical asthma. PMID- 4039345 TI - [A case with non-gestational choriocarcinoma of the uterus]. PMID- 4039346 TI - Loss of platelet alpha 2-adrenergic receptors during simulated extracorporeal circulation: prevention with prostaglandin E1. AB - Cardiopulmonary bypass prolongs bleeding time and increases postoperative blood loss. During in vitro recirculation in an extracorporeal circuit containing a membrane oxygenator and primed with fresh heparinized human blood, we previously observed thrombocytopenia, impaired platelet aggregation, and depletion of granular contents, all of which were prevented with prostaglandin E1 (PGE1). To investigate these changes further, we studied the number and affinity of platelet alpha 2-adrenergic receptors by measuring the binding of 3H-yohimbine. Before recirculation, we found 235 +/- 28 alpha 2-adrenergic receptors per platelet, a Kd of 3.37 +/- 0.78 nmol/L, complete aggregation with 1.04 mumol/L epinephrine, and a platelet count of 281,000 +/- 33,000 microliters-1. After 2 minutes of recirculation, 9.44 mumol/L epinephrine was required to produce complete aggregation, and the platelet count was 104,000 +/- 22,000 microliters-1 (44% of control). The number of binding sites significantly decreased to 139 +/- 16 per platelet, but the affinity did not change (Kd = 3.78 +/- 0.44 nmol/L). After 2 hours of recirculation, the platelet count had increased to 123,000 +/- 21,000 microliters-1. However, epinephrine did not induce platelet aggregation even at 100 mumol/L. Moreover, alpha 2-adrenergic binding sites were not detectable, and affinity for yohimbine could not be calculated. Two minutes after PGE1 0.3 mumol/L was added to the circuit, platelet numbers, response to epinephrine, alpha 2-adrenergic binding sites per platelet, and affinity for yohimbine were not significantly different from control values. At 2 hours, the number of alpha 2-adrenergic sites was not significantly changed from control, but the affinity of yohimbine for platelets was significantly decreased 2.5-fold.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4039347 TI - Structure of biologically active and inactive cerebrosides prepared from Schizophyllum commune. AB - A cerebroside fraction prepared from the mycelia of Schizophyllum commune was further fractionated into five components (I-V) by reverse-phase high-performance liquid chromatography. Fruiting-inducing activity was found in I-IV but not in V. By gas-liquid chromatography-mass spectrometry and nuclear magnetic resonance analyses it was shown that these fractions contained: I, a mixture of N-2' hydroxypentadecanoyl-1-O-glucosyl-nonadecasphingadienine++ + and N-2' hydroxyhexadecanoyl-1-O-glucosyl-sphingadienine; II, (4E,8E)-N-D-2' hydroxyhexadecanoyl-1-O-beta-D-glucopyr anosyl-9-methyl-4,8- sphingadienine (Kawai and Ikeda. 1983. Biochim. Biophys. Acta. 754: 243-248); III, N-2' hydroxyheptadecanoyl-1-O-glucosyl-nonadecasphingadienine++ +; IV, N-2' hydroxyoctadecanoyl-1-O-glucosyl-nonadecasphinadienine; V, (4E,8E)-N-2' hydroxytetracosanoyl-1-O-beta-glucopyrano syl-9-methyl-4,8- sphingadienine. The only structural difference observed between biologically active and inactive cerebrosides was the chain length of acyl moiety; the cerebroside having an acyl chain of 24 carbon atoms was inactive. PMID- 4039348 TI - Hypertrophic cardiomyopathy in childhood: Part II. PMID- 4039349 TI - Reappraisal of the influence of mammary distension on the frequency of milk ejection in the rat. AB - Experiments were performed to reinvestigate the importance of mammary engorgement for activation of the milk-ejection reflex in the rat. Reflex milk ejection (measured by intramammary pressure recordings during a 2-h suckling test under anaesthesia) was compared in rats with engorged mammary glands (15-h separation from the pups, followed by sham-removal of milk) and in rats with drained mammary glands (15-h separation, followed by milk removal using a foster litter and exogenous oxytocin). In experiment 1, multiple small (2 mu.) doses of oxytocin were used for milk removal: these were effective in emptying the mammary glands and caused no subsequent impairment or change in sensitivity of the mammary response to oxytocin. Using this draining procedure, no significant differences were observed in either the number or relative amplitude of the milk ejections, or the occurrence of pup stretch reactions between engorged and drained rats. Similar results were seen in experiment 2, where an identical draining protocol was used, but the rats were pretreated with propranolol before the suckling test. In experiment 3, large (250 mu.) oxytocin doses were used for milk removal, as in previous studies. Again mammary draining had no effect on milk ejection in a subsequent suckling test (with propranolol pretreatment). However, the number of stretch reactions shown by the pups was significantly (P less than 0.001) reduced from 8.6 +/- 1.4/2 h to 1.9 +/- 0.6/2 h. This effect probably related to long term impairment of the oxytocin response of the mammary glands following the draining procedure, and could not be attributed to the draining per se.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4039350 TI - Fasting impairs LH secretion in female rats by activating an inhibitory opioid pathway. AB - Two experiments were undertaken to investigate the way that fasting impairs LH secretion and to assess whether endogenous opioid mechanisms might be responsible for the impairment. In the first experiment, pulsatile LH secretion was measured in a total of 51 chronically ovariectomized female rats. Initially 29 rats were subjected to food withdrawal for 24, 48, 72 or 120 h before the experiment. When compared with data collected from eight unfasted control rats, the 120-h fast was found to reduce significantly the mean peak and trough values of the LH pulses measured. However, in a subsequent study, the inhibition of pulsatile LH secretion by a 120-h fast was prevented in a group of eight rats given the opioid antagonist naloxone hydrochloride before the start of the blood-sampling period. Naloxone was without effect on pulsatile LH secretion in eight unfasted control rats. In the second experiment, plasma LH concentrations were measured before and after unilateral electrical stimulation of the ventral noradrenergic tract (VNAT) in ovariectomized female rats pretreated with oestradiol benzoate. In 17 rats VNAT stimulation caused a significant rise in plasma LH, but after a 72-h fast this rise was significantly less than in unfasted control rats. However, pretreatment of fasted rats with naloxone (n = 9) significantly enhanced the VNAT stimulated release of LH to the control values. Naloxone did not potentiate VNAT stimulated LH release in unfasted animals (n = 6) or LH release in control unstimulated rats (n = 12). The experiments indicate that both pulsatile LH secretion, and LH release caused by VNAT stimulation, are impaired by an acute fast.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4039351 TI - The genetic background of circadian and ultradian rhythm patterns of 17 hydroxycorticosteroids: a cross-twin study. AB - Circadian and ultradian rhythms in urinary excretion of 17-hydroxycorticosteroids were documented individually during an 8-day span in two pairs of young male twins. Studies were performed once at the age of 6 years for dizygotic twins and twice at the ages of 4.3 and 10.3 years for monozygotic twins. Four different methods were used for time-series analyses: chronograms (raw data), best-fitting curves resulting from cosinor analyses, power spectra and correlations of time qualified data. Estimates of rhythm parameters (prominent periods, acrophases, etc.) as well as shapes of curves were closer in mono- than in dizygotic twins. Both similarities and small differences in rhythm characteristics of monozygotic twins were detected at both ages considered. PMID- 4039352 TI - Odour recognition by male hamsters: discrimination of the hormonal state of females by odour from vaginal secretions. AB - Male hamsters were tested for their interest in females on different days of the oestrous cycle. Behaviour of males toward novel females was measured and (after exposure to vaginal secretion) towards females that matched or did not match that vaginal odour. Because pro-oestrous (day 4) females lay trails of vaginal secretion and will become receptive within a few hours, it was predicted that males would show more interest in day 4 than in other dioestrous females. While males showed no preference for novel, pro-oestrous females over dioestrous females, after pre-exposure to odour, their response to females was determined by the cycle day of the vaginal secretion to which they had been exposed. Males pre exposed to vaginal odour from females carrying large implants of oestrogen preferred to spend more time with females who matched that vaginal odour than mismatching females and to sniff them more. This preference was not seen if the females carried small oestrogen implants or had no replacement oestrogen. This suggests that pro-oestrous females (who are known to have high circulating levels of oestrogen) can, by means of their scent-marking behaviour, attract and keep males nearby until they become receptive. PMID- 4039353 TI - Mortality ratios and life expectancy in X chromatin positive males. AB - In a prospective study of 466 X chromatin positive males an increase in mortality of about 50% has been observed. The increase is associated with a loss of about five years in life span. There is no convincing evidence that the increase is concentrated at any particular age group but this possibility could not be excluded. No effect of mode of ascertainment could be demonstrated. From this study we conclude that it is likely that the mortality experienced by chromatin positive males in general is at least 115% of that experienced by normal men and could be more than 200%. PMID- 4039354 TI - Sib risk and the dizygotic twin concordance rate for multiple sclerosis. AB - Data have been reviewed on sib risk and the dizygotic twin concordance rate in multiple sclerosis. Even when rigorous criteria are applied, the dizygotic twin concordance rate for multiple sclerosis is apparently higher (perhaps 10 times higher) than could be explained by the sib risk. In contrast, twins with Parkinson's disease have low concordance rates even when ascertainment is by informal methods. It is concluded that such methods of ascertainment are not as biased as has been suggested, and that the high concordance rates reported for multiple sclerosis are a characteristic of the disease rather than an artifact of the ascertainment. Three hypotheses are considered which might, in principle, explain this high dizygotic twin concordance rate in multiple sclerosis: 1 One is certainly false, viz, that it is due to an excessive liability of dizygotic twins to the disease. 2 It is possible that a pathogen occurs in early infancy or in pregnancy itself. 3 It seems more likely that the high concordance rate may be explained in terms of age related events or sequences of events. (If such events were pathogenic for one member of a sibship, they would be pathogenic for another only if it were a co-twin). PMID- 4039355 TI - Cell surface changes during cleavage of newt eggs: scanning electron microscopic studies. AB - Scanning electron microscopic studies were carried out on changes of the cell surface during the first cleavage of eggs of the newt, Cynopus (Triturus) pyrrhogaster. A dense population of elongated microvilli, which initially covered a double line indicating the initial furrow and stress marks running on each side of it, became located inside the pigmented area a little apart from its border with the unpigmented area when this borderline was established. This finding, together with data of carbon marking experiments, indicates that membrane growth occurs not only at the presumptive unpigmented surface, but also in a small portion of the presumptive pigmented area adjoining it. During cleavage within the vitelline membrane, a stable intercellular junction at the border of the pigmented and unpigmented surfaces was formed through the following successive processes: the appearance of individual lamellipodia on the borderline; contact of their apical filopodia with those of the opposite blastomere; contact of the lamellipodial bodies; and complete joining of the whole of the lamellipodia in contact. In cleavage of demembranated eggs, in which there is no chance of contact of lamellipodia of the two blastomeres, each lamellipodium persisted in an isolated state until the onset of the next division. In most cases, many strained or broken threads were seen across the space formed by opening of opposing blastomeres, at their peripheries. These threads were cytoplasmic in nature and showed cell contact. Similar threads were found stretched between blastomeres when the closed furrow was opened in medium containing EGTA. PMID- 4039356 TI - Localization of the factors producing the periodic activities responsible for synchronous cleavage in Xenopus embryos. AB - This paper investigates the localization within the Xenopus egg of the factors responsible for the periodic activities such as the cyclic rounding-up and flattening, related to the cleavage cycle. Denuded eggs were bisected along the boundary line between the animal and the vegetal hemispheres immediately after being rotated through 90 degrees off the vertical axis (Early Bisection). The resulting animal halves, though prevented from cell division by colchicine, showed typical periodic rounding-up as previously observed in enucleated egg fragments, whereas the vegetal halves did not. This result indicates that the factors inducing the periodic rounding-up are not distributed uniformly throughout the egg but localized mostly in the animal hemisphere. Furthermore, the distribution of these factors between the cortex and endoplasm of the animal hemisphere was investigated. Eggs were separated into animal and vegetal halves following incubation for 30 min after the 90 degrees-off axis rotation (Late Bisection). During this incubation the endoplasmic components become relocated in the rotated egg under the force of gravity. After the rotation, the Late-Bisected vegetal halves showed typical cyclic rounding-up in contrast to those formed by Early Bisection. These results suggest that the factors inducing the periodic rounding-up (and probably also many other cyclic activities, closely linked with the rounding-up movement) are localized in endoplasmic components which can be displaced by gravity from the animal to the vegetal hemisphere of the Xenopus egg. PMID- 4039357 TI - Protein synthetic patterns of tissues in the early chick embryo. AB - Tissues dissected from early chick embryos were labelled in vitro with [35S]methionine, and their patterns of polypeptide synthesis investigated using the technique of two-dimensional (2-D) polyacrylamide gel electrophoresis. Apart from providing a preliminary description of the molecular changes associated with the processes of gastrulation and segmentation in the chick embryo, this study has revealed a number of polypeptides that may be useful as markers of cell type or function. The protein synthetic patterns of hypoblast from early and late gastrulae (stages 2 and 4, respectively: Hamburger & Hamilton, 1951) and of definitive endoblast and junctional endoblast from late gastrulae all resemble one another closely, but differ markedly from that of the epiblast at either stage. The lower layer tissues are characterized by the presence of eleven polypeptides that are largely absent from the epiblast. These findings are discussed with reference to current theories on the origins of the lower layer tissues. Comparisons between the 2-D patterns for tissues dissected from gastrulae and from embryos undergoing segmentation (stage 12) have revealed ten polypeptides showing stage-specific rather than tissue-specific expression. Apart from these ten polypeptides, the 2-D patterns for epiblast and ectoderm were practically identical, and distinguishable from those of other tissues by a lack of any unique polypeptides. On the other hand, stage-4 endoblast and stage-12 endoderm differed in the expression of many polypeptides. One polypeptide was found that may be considered as a marker of mesodermal cell type, as it was present in lateral plate, segmental plate and somitic mesoderm, but not in tissues of the other germ layers. Lateral plate could be distinguished from the other mesodermal tissues in the expression of a number of polypeptides, but the similarity in the 2-D patterns for segmental plate and somites suggest that the separation of somites from the anterior end of the segmental plate is not accompanied by the synthesis of new polypeptides. PMID- 4039358 TI - Short-term and long-term intra-individual variations and critical differences of haematological laboratory parameters. AB - The complete blood cell count and the differential leukocyte count have been studied for their variations within-one-day and during one week (short-term variations) and during a period of six months (long-term variations) with an automatic haematology analyser (H-6000, Technicon), in which some new parameters (large unstained cells, high peroxidase cells, red cell distribution width, platelet distribution width, mean platelet volume, plateletcrit) are included. The influence of external factors such as sex-differences, smoking/non-smoking, use of oral contraceptives etc. have also been studied. It appears that the use of critical differences together with haematological data improves the value of these parameters in diagnosis and treatment of patients. PMID- 4039360 TI - Delayed renal visualization during hepatobiliary scintigraphy. PMID- 4039359 TI - Brain glutamate decarboxylase and cholinergic enzyme activities in scrapie. AB - C57BL/6J mice, age 6-8 weeks were inoculated intracerebrally with brain homogenate from mice previously infected with the 139A strain of scrapie; control mice were identically treated with brain homogenate from non-infected normal mice. The activities of choline acetyltransferase (CAT), acetyl cholinesterase (AChE), and glutamic acid decarboxylase (GAD) were determined in the forebrain and hindbrain of these animals after 67, 126 and 151 days post-inoculation. There were no significant differences in the activities of CAT and GAD between scrapie and control mice at early, middle or late stages of the disease in the scrapie infected animals; there was an about 20% decline in AChE activity in the scrapie brain. PMID- 4039361 TI - Zinc in human milk: diurnal and within-feed patterns. AB - To examine diurnal patterns of milk zinc concentrations, midfeed samples were obtained at approximately 6 a.m., 9 a.m., 12 noon, 3 p.m., 6 p.m., and 9 p.m. on a total of 29 days from 16 lactating women. Within-feed patterns were examined in 32 subjects with analysis of samples of fore-, mid-, and hindmilk from a total of 175 feeds. There were no significant differences between means for any of the diurnal intervals or between means for fore-, mid-, and hindmilk samples. These results indicate that milk zinc concentrations of random samples of human milk collected at any time of the day or of the feed can be accepted as representative for that day. PMID- 4039362 TI - Characteristics of the oestrous cycle and influence of social factors in grey short-tailed opossums (Monodelphis domestica). AB - Characteristics of the oestrous cycle of grey short-tailed opossums were studied by vaginal smears. The period of oestrus was identified by a sudden proliferation of epithelial cells which lasted about 6 days (range 3-12 days), followed by a leucocytic infiltration. Oestrous cycle length showed a bimodal distribution of 14.4 days (5 cycles, range 11-17 days) and 32.3 days (10 cycles, range 28-39 days). Females housed with males showed more days of epithelial cell proliferation than did females housed alone, and oestrous periods tended to occur in synchrony, suggesting that social factors may influence the oestrous cycle in this species. PMID- 4039363 TI - Effects of progesterone, oestradiol benzoate and cloprostenol on luteal function in the heifer. AB - The effects of treatment with intravaginal progesterone (PRID) oestradiol benzoate and cloprostenol at various stages of the oestrous cycle were examined in 2 experiments. In Exp. 1, PRIDs were inserted for 14 days commencing on Day 3, 10 or 17 of the oestrous cycle and half the animals in each group received 5 mg oestradiol benzoate at PRID insertion. Plasma samples were collected daily from the time of PRID insertion for 16 days, then every 4 days for a further 24 days. Samples were analysed for plasma progesterone concentration. In Exp. 2, heifers were treated on Day 10 as in Exp. 1, but half of each treatment group received 750 micrograms cloprostenol at PRID insertion. In Exp. 1, treatment with PRID alone appeared to inhibit endogenous progesterone production when treatment began on Day 3, but not when treatment began on Days 10 or 17. Treatment with oestradiol benzoate at the time of PRID insertion depressed progesterone levels, from about 2-5 days after injection. When treatment began on Day 10, the fall in progesterone levels after oestradiol benzoate was preceded by a marked rise in levels. In Exp. 2, treatment with cloprostenol markedly reduced peripheral concentrations of progesterone and also removed the effect of oestradiol. We suggest that oestradiol benzoate had a luteolytic effect, depressing luteal progesterone production when given on Days 3, 10 or 17 and that when given on Day 10 there was a transitory luteotrophic effect which preceded its luteolytic action. PMID- 4039364 TI - Structural and functional changes in ovaries from adult mice treated with diethylstilboestrol in the neonatal period. AB - Ovaries from 8-week-old female NMRI mice in different stages of the oestrous cycle, or from females neonatally treated with the synthetic oestrogen diethylstilboestrol (DES; 5-10(-6) micrograms daily for 5 days), were studied histologically and for the ability to synthesize steroids from [3H]pregnenolone in vitro. Daily doses of 10(-4) micrograms DES or higher resulted in absence of corpora lutea. In ovaries lacking corpora lutea, the interstitial tissue dominated and the cells in this compartment were large with a clear cytoplasm. The steroids synthesized in ovarian homogenates were separated with thin-layer chromatography. The homogeneity of the steroids was checked in recrystallization experiments. Daily doses of 5-10(-4) micrograms DES in the neonatal period resulted in pronounced deviations in the pattern of ovarian steroids synthesized as compared with control ovaries. In DES-exposed ovaries, the synthesis of androstenedione and, above all, progesterone was high while the synthesis of 17 alpha-hydroxyprogesterone and testosterone was reduced compared with controls. These results could argue for a difference in activities of 17 alpha-hydroxylase and 17 beta-ol-dehydrogenase in ovaries from DES-treated females compared with controls. After transplantation of DES-exposed ovaries to ovariectomized control females, the steroid pattern changed to that typical for control ovaries. Control ovaries transplanted to DES-treated females had a steroid pattern similar to that of DES-exposed ovaries. PMID- 4039365 TI - Metabolism of palmitate in cultured rat Sertoli cells. AB - Isolated rat Sertoli cells were incubated in the presence of [1-14C]palmitate at a cell concentration of 1.54 +/- 0.31 mg protein/flask (n = 7). The oxidation of palmitate was concentration dependent and maximal oxidation was obtained at 0.35 mM-palmitate. At a saturating concentration of palmitate the oxidation was linear for at least 6 h. About 65% of the total amount of palmitate oxidized during 5 h at 0.52 mM-palmitate (109 +/- 44 nmol/flask, n = 5) was recovered as CO2 and the rest as acid-soluble compounds. Almost all radioactive acid-soluble compounds which were secreted by the Sertoli cells were shown to be 3-hydroxybutyrate and acetoacetate. The palmitate recovery in cellular lipids and triacylglycerols was 9.4 +/- 5.1 nmol/flask (n = 5) and 3.5 +/- 2.8 nmol/flask (n = 5) respectively. Addition of glucose had no significant effect on palmitate oxidation but caused a 9-fold increase in esterification of palmitate into triacylglycerols. We conclude that cultured rat Sertoli cells can oxidize palmitate to CO2 and ketone bodies and that fatty acids appear to be a major energy substrate for these cells. PMID- 4039366 TI - Early evening prolactin rise in women with regular cycles. AB - Prolactin concentrations were measured in hourly integrated blood samples collected over 24 h in normally cyclic women during the follicular (N = 8) and the luteal (N = 7) phases of the menstrual cycle. Prolactin concentrations were increased during the evening in all the subjects when compared with the rest of the day-time wake-period. This rise was unrelated to sleep, and peak concentrations were seen at 20:00 h. During the luteal phase the magnitude of this evening rise of prolactin was significantly greater (P less than 0.02 at 19:00 h and P less than 0.001 at 20:00 h) when compared with the follicular phase, and was only slightly smaller than the magnitude of the sleep-induced prolactin rise. It is therefore suggested that there may be an intrinsic rhythm in prolactin secretion apart from the sleep-induced rise. PMID- 4039367 TI - Response in peripheral plasma melatonin to photoperiod change and the effects of exogenous melatonin on seasonal quiescence in the tammar, Macropus eugenii. AB - During the light phase of each of 3 photoperiods tested, plasma melatonin concentrations were less than 16 to 62 pg/ml and during the dark phase they were 31 to 169 pg/ml. When the photoperiod to which the tammars were exposed was altered from 15 h light:9 h dark to 12L:12D the onset of the nocturnal rise in melatonin was advanced from the first day, thereby extending its duration, and the females gave birth 32 +/- 0.4 (mean +/- s.e.m.) days later. To test whether melatonin mediated this effect of photo-period change, tammars in a second group were injected s.c. with melatonin (400 ng/kg, N = 6) or the arachis oil vehicle (N = 6), 2.5 to 2.25 h before dark during 15L:9D for 15 days before exposure to 12.5L:11.5D. The melatonin injections mimicked the endogenous melatonin profile of 12L:12D and the melatonin-injected tammars gave birth 32 +/- 0.8 days after the start of injections, which was the same as the interval from photoperiod change in Exp. 1 but was significantly different (P less than 0.005) from the interval in the control group (46.0 +/- 1.1 days). These results show that exogenous melatonin given 2.5 to 2.25 h in advance of the endogenous rise fully mimics the response of the tammar to photoperiod change. PMID- 4039368 TI - Synthesis and central dopaminergic effects of N-(4,6-dimethyl-2 pyridinyl)benzamides. AB - N-(4,6-Dimethyl-2-pyridinyl)benzamides 1-24 and the corresponding tertiary derivatives 29-33 were synthesized and studied for possible dopamine-inhibitory properties by testing their effect on motility of naive and reserpinized mice. Unlike the orthopramides, they failed to show any antidopaminergic properties, but some of the secondary derivatives showed instead effects of postsynaptic dopaminergic agonism. The latter compounds were subsequently studied for their effects on apomorphine reversal of reserpine-induced akinesia and on cerebral HVA levels in rats. Contraversive circling induced by compound 11 in 6 hydroxydopamine-lesioned mice suggests that a direct mechanism was involved. PMID- 4039369 TI - Resolution of 5,6-dihydroxy-2-(N,N-di-n-propylamino)tetralin in relation to the structural and stereochemical requirements for centrally acting dopamine agonists. AB - The enantiomers of 5,6-dimethoxy-2-(N,N-dipropylamino)tetralin were prepared with use of (+)- and (-)-dibenzoyltartaric acid as the resolving agent. Ether cleavage with BBr3 gave the enantiomers of the dihydroxy compound 5,6-dihydroxy-2-(N,N dipropylamino)tetralin (5,6-(OH)2-DPATN). The in vitro activities of (+)- and (-) 5,6-(OH)2-DPATN were evaluated in binding studies with rat striatal tissue with use of [3H]-N-n-propylnorapomorphine (NPA) as the ligand. IC50 (nM) values for ( )- and (+)-5,6-(OH)2-DPATN were 2.5 and 400, respectively. The in vivo efficacy of the enantiomers was evaluated by examining their effects on the metabolism of dopamine in rat striatum. After a 0.5 mumol/kg ip injection of the (-) enantiomer, the concentrations of the metabolites HVA and DOPAC were reduced to 50% of control values, whereas at this dose the (+) isomer was inactive. On the basis of these findings together with the stereochemical data of previously described DA agonists, a dopamine-receptor model has been developed which consists of two binding sites for the amine nitrogen of DA agonists in addition to a major binding sit for the m-hydroxy group. The relevance of this model with its accessory features is discussed in relation to the structure and pharmacological data of different DA agonists. PMID- 4039370 TI - Frequency and replication status of the fragile X, fra(X)(q27-28), in a pair of monozygotic twins of markedly differing intelligence. AB - Chromosome analysis using conventional staining, G banding, and, after BUdR incorporation, two R banding methods, one using Hoechst and one acridine orange, were performed on lymphocytes from a pair of female monozygotic twins. The culture conditions were designed to show the presence of the fragile X (q27-28) which had previously been found to be segregating in the family. One twin was of higher than normal intelligence and the other had been diagnosed as mentally retarded. The frequency of the occurrence of the early/active fragile X compared to the overall total of informative fragile X was determined using both methods described above and was also compared with previous published data in the form of a graph showing percentage of early/active fragile X against intelligence. PMID- 4039371 TI - Sex therapy and the penile prosthesis: a synthesis. AB - Although the availability of the penile prosthesis has changed the evaluation and treatment of erectile dysfunction, urologists and sex therapists have not combined their skills to develop comprehensive treatment plans. This paper describes one effort to use sex therapy techniques in evaluating and treating candidates for a penile prosthesis. The preoperative assessment focuses on multiaxial diagnosis of sexual problems in patient and partner and on the effects a prosthesis might have on their sexual and marital relationship. Men at high risk for a negative psychological reaction after surgery are offered presurgical sex therapy. Routine follow-up visits are scheduled for all patients during postoperative recovery and at 2-3 months postsurgery. If sexual dysfunction or dissatisfaction persists, sex therapy is again recommended. A case history exemplifies our methods, and the issue of financial costs of counseling vs. predicted benefits in terms of patient satisfaction is discussed. PMID- 4039372 TI - Recurrent or persistent urinary incontinence in patients with the artificial urinary sphincter: diagnostic considerations and management. AB - Clinical experience in the selection of patients for implantation of the artificial urinary sphincter and the surgical techniques for sphincter implantation indicate a need to provide suitable guidelines for patient followup and the management of post-implantation urinary incontinence. Two types of post implantation incontinence are recognized: 1) immediate post-activation incontinence and 2) delayed or recurrent incontinence. The potential causes, and the diagnostic and management techniques are dependent on not only an understanding of device function but also on the use of already available clinical tools. Physical examination, inflate-deflate roentgenograms of the device, cystoscopy and retrograde urethrography each has an important role in determining the cause and, therefore, the appropriate remedy for the restoration of urinary control. Causes that result in loss of urinary control after implantation include improper operation of the device by the patient, detrusor hyperreflexia, occlusive cuff erosion, improper cuff sizing and device malfunction. Proper recognition of the precise cause of post-implantation incontinence and workable guidelines for management will provide for effective assurance that urinary control can be restored successfully. PMID- 4039373 TI - Urethral sphincter electromyography with vaginal surface electrodes: a comparison with sphincter electromyography recorded via periurethral coaxial, anal sphincter needle and perianal surface electrodes. AB - Urethral sphincter electromyography recording via vaginal surface electrodes was compared to simultaneous sphincter electromyographic registrations obtained with a periurethral coaxial needle electrode and perianal surface or needle electrodes in 10 neurologically intact women. Qualitative similarity of the vaginal surface and periurethral needle electrode recordings was found. Based on this and our previous studies, we conclude that electromyographic recording with vaginal surface electrodes offers a simple and reliable technique to evaluate the striated urethral sphincter during routine urodynamic studies in women. PMID- 4039374 TI - The effect of 15-hour fat infusions of varying dosage on bilirubin binding to albumin. AB - Intravenous fat emulsions (1, 2, and 3 g/kg) were administered over 15 hr to 20 appropriate for gestational age premature infants with physiologic hyperbilirubinemia to determine the effect of fat infusions on the serum free fatty acid:albumin molar ratio (F/A) and on unbound bilirubin. Significant increases (p less than 0.05) in F/A occurred with each increase in lipid dose in infants less than 30 wk gestation, but not in infants greater than or equal to 30 wk gestation. There was a direct linear correlation (r = 0.65, p less than 0.001) between F/A ratio and unbound bilirubin (estimated fluorometrically by the ratio of albumin-bound bilirubin/reserve bilirubin binding capacity, B/R). The largest increases in unbound bilirubin (albumin-bound bilirubin/reserve bilirubin binding capacity) were seen in infants with F/A greater than 4.0. The gestational age of infants with F/A greater than 4.0 was significantly less (p less than 0.01) than infants with F/A less than 4.0 (28.7 +/- 0.47 vs. 31.1 +/- 0.40 wk, mean +/- SEM). In 10/58 infusions there was a fall in unbound bilirubin, unrelated to birthweight, gestational age, postnatal age, however, during these infusions the end-infusion F/A was greater than or equal to 3.0. We conclude that 1 g/kg of lipid emulsion infused over a 15-hr period has minimal risk of decreasing bilirubin binding in premature infants less than 30 wk gestation. As doses of 2 or 3 g/kg are used, these infants may be at risk of decreased bilirubin binding, due to elevations in the F/A ratio. Monitoring of the F/A ratio may identify infants at risk for decreased bilirubin binding during lipid infusion and provide guidelines for determining the appropriate lipid dose. PMID- 4039375 TI - Systemic appearance of nutrients placed into the peritoneal cavity. AB - The use of the peritoneal cavity as a route for delivery of nutrients in patients on continuous ambulatory peritoneal dialysis as well as patients not in renal failure has been proposed. In earlier studies we found dogs could be maintained for 30 days through continuous peritoneal infusion of a solution of amino acids, glucose, and lipids. We then conducted experiments to observe the rate of absorption of nutrients from the gut compared to the peritoneal cavity, the relative rate absorption of amino acids, sugars, and fats, and the absorption of of glucose polymers from the peritoneal cavity. These latter experiments are the subject of this report. In a dog model we observed D-xylose was more rapidly absorbed through the peritoneal cavity than through the gut, but amino acids were absorbed at the same rate. Glucose and amino acid are absorbed at the same rate through the peritoneal cavity, but lipids do not appear in the system circulation for 2 1/2 hr. Intraperitoneal glucose polymer produces an increase in serum glucose concentration that is lower and more sustained than what occurs after giving an equal amount of plain glucose. It is concluded that the peritoneal cavity rapidly transports glucose, amino acids, and glucose polymers and slowly transports lipids into the systemic circulation. Consideration of this route for delivery of nutritional support seems reasonable, but further studies of appropriate concentrations and rates of delivery will be required. PMID- 4039376 TI - The effect of major thermal injury on plasma ketone body levels. AB - Eleven patients with more than 30% total body surface burns were studied during 3 days of starvation and three more days of unrestricted feeding following their injury. All patients developed marked protein mobilization as demonstrated by 3rd day urine nitrogen excretion of 17.1 g daily compared to control excretion of 11.8 g N daily. As a group, the patients failed to mount the expected ketonemic response during their initial period of starvation. Whereas normal fasted controls achieved plasma ketone body levels of 727 +/- 81 mumol/liter, the burn patients responded with an average level of 385 +/- 77 mumol/liter (p less than 0.01). PMID- 4039377 TI - The value of nutritional assessment in the surgical patient. AB - The prevalence of malnutrition in Veterans Administration Hospitals has been well documented. Several methods have been proposed to assess nutritional status including prognostic nutritional index (PNI) and instant nutritional assessment (INA). A prospective study was done to evaluate the currently used nutritional assessments and determine their efficacy based on sensitivity and specificity in predicting surgical morbidity and mortality. Data on 46 patients were evaluated for the multiparameter index of PNI, total lymphocyte count and serum albumin for INA, and weight loss alone. In this analysis, intermediate and high risk PNI were combined as positive predictor of complications. Any abnormal value in INA was considered positive as was weight loss of greater than 6% of usual body weight. Sensitivity and specificity of each assessment method were determined by 2 X 2 contingency table, and significance of observed differences between methods was determined by chi 2 analysis. There were no complications or deaths in patients with less than 6% weight loss. All three patients with abnormal albumin and total lymphocyte count had complications as compared to only three of 32 patients when both of these parameters were normal. The PNI was also able to predict complications with an increasing incidence as the PNI increased. Only the difference between specificity of weight loss alone vs INA was statistically significant, p less than 0.05. Thus, weight loss alone can be used as a rapid, inexpensive assessment of nutritional status for predicting postoperative complications. PMID- 4039379 TI - Postoperative fall in serum zinc concentrations unaffected by intravenous zinc therapy. AB - The serum zinc levels and urinary zinc outputs before and after a middle severity operative trauma were investigated. The serum zinc concentration dropped markedly 6 hr after operation in both supplemented and nonsupplemented groups. It gradually returned to near normal without exogenous supplies of zinc. Provision of therapeutic doses of zinc could not prevent the abrupt dip of the serum zinc level. The possible mechanism of such changes are discussed briefly. PMID- 4039378 TI - Nitrogen utilization from elemental diets. AB - Repletion experiments were performed in malnourished, chair-adapted primates to explore recently reported differences in nitrogen utilization from elemental diets. Two elemental diets were fed consecutively for 8 days through a gastrostomy. Diet C (maltodextrins, peptides, crystalline amino acids) resulted in: larger weight gain (F1,6 = 17.93, p less than 0.01); smaller decrease of serum albumin (F1,5 = 11.2, p less than 0.015), larger increase in total iron binding capacity (F1,6 = 30.6, p less than 0.002), and a more positive nitrogen balance (F1,6 = 30.4, p less than 0.002) than diet V (glucose oligosaccharides, crystalline amino acids). Diet C was considered to be more effective in the nutritional repletion of the study animals. Additional experiments were performed in normal human volunteers to investigate the metabolic fate of ingested glutamine and whether the rapid catabolism and excretion of the amido nitrogen of this amino acid, which constitutes 11.56% of total nitrogen in diet V, could explain the differences observed in primates in our study and in human subjects by other authors. Six normal volunteers were fed 15N amino glutamine, 15N alanine, or 15N H4Cl. Similar amounts of 15N from Gln and Ala were excreted in 10 hr. The amido group of glutamine does not seem to be metabolized differently from the alpha-amino group of alanine under the conditions of the study. The marked differences in nitrogen utilization from the study diets could not be explained by the presence of relatively large amounts of glutamine in one of them. PMID- 4039380 TI - Creation of a subcutaneous tunnel for Broviac and Hickman catheters. AB - The use of the Cordis shunt tunneler has simplified the creation of the subcutaneous tunnel for chronic venous access catheters. The tunneling maneuver is rapid, is associated with little patient discomfort, and in a series of 25 consecutive patients has not been associated with hematoma formation. PMID- 4039381 TI - Delayed pneumothorax: a complication of subclavian vein catheterization. PMID- 4039382 TI - [The cytotoxicity of chenodeoxycholic acid on primary cultured rat hepatocytes and cytoprotective action of prostaglandin E1]. PMID- 4039383 TI - [Production of erosions and ulcers of the colon in Syrian hamsters with Bacteroides vulgatus isolated from the fecal microflora of human ulcerative colitis]. PMID- 4039384 TI - Methionine-enkephalin inhibits stress-induced increases in noradrenaline turnover in brain regions of rats. AB - Met-Enkephalin injected i.c.v. attenuated stress-induced increases in levels of 3 methoxy-4-hydroxyphenylethyleneglycol sulfate, the major metabolite of brain noradrenaline, in the hypothalamus, amygdala, hippocampus, thalamus, midbrain and LC region in rats. The data suggest that Met-enkephalin acts to attenuate stress induced increases in noradrenaline turnover in these brain regions in rats. PMID- 4039385 TI - Effect of elcatonin on experimental gastric and duodenal ulcers. AB - The antiulcer action of elcatonin, an analogue of natural eel calcitonin, was compared with that of cimetidine, secretin and solcoseryl. Elcatonin (3 to 10 mu/kg, s.c.) inhibited the development of gastric ulcers induced by pylorus ligation, water-immersion stress, aspirin and reserpine and duodenal ulcers induced by cysteamine in rats. Moreover, once daily injections of elcatonin (1 to 10 mu/kg/day, s.c.) promoted the healing of acetic acid-induced chronic gastric ulcers not only in rats but in dogs. The healing effect persisted after the cessation of administrations. Cimetidine (30 to 100 mg/kg, p.o.) inhibited the development of gastric ulcers induced by water-immersion stress, aspirin and reserpine and duodenal ulcers induced by cysteamine in rats. However, once daily administrations of cimetidine (30 to 100 mg/kg/day, p.o.) did not show significant effect on acetic acid-induced chronic gastric ulcers in rats. Secretin (30 to 100 mu/kg, s.c.) inhibited the development of gastric ulcers induced by pylorus ligation, water-immersion stress, aspirin and reserpine in rats, but was not effective on cysteamine-induced duodenal ulcers and acetic acid induced chronic gastric ulcers in rats. Solcoseryl (2 ml/kg, s.c.) inhibited only the development of water-immersion stress-induced gastric ulcers in rats. These results suggest that elcatonin is different from these reference drugs in its properties of action on experimental ulcers. Mechanisms of the antiulcer action of elcatonin which has a superior effect on experimental ulcers are discussed. PMID- 4039386 TI - [Comparative evaluation of the effect of preliminary adaptation of the body to moderate physical loading and brief stress exposures on heart contractile function disorders in long-term stress]. AB - The effect of repeated emotional-painful stress stimuli and repeated moderate exercise (swimming) on cardiac resistance to long-term emotional-painful stress (EPS) was studied in Wistar rats. Adaptation to repeated exercises was found to significantly increase tension developed by the myocardium of an isolated auricle and myocardial resistance to hypoxia and excessive calcium, but it could not prevent the EPS-induced depression of contractility. Adaptation to short-term stress on the contrary, did not significantly affect myocardial tension and cardiac resistance to hypoxia and excessive calcium, but it completely prevented the long-term EPS-induced depression and considerably reduced the stress potentiating effect on the development of calcium and hypoxic contractures. Therefore, adaptation to stressful effects proper, rather than moderate exercise, can build up heart resistance to damaging stress effects. PMID- 4039387 TI - Peritoneal permeability in the rat: modulation by microfilament-active agents. AB - A model of peritoneal dialysis in the rat was used to determine the effects of cytochalasins on ultrastructure and peritoneal permeability to molecules of varying molecular weight. The permeability to urea, inulin, and plasma albumin were determined after intraperitoneal administration of cytochalasin B (2 to 10 X 10(-6) M) and cytochalasins D and E (2 X 10(-6) M). Cytochalasin B (20 X 10(-6) M) increased the permeability to inulin, urea, and albumin by 30, 60, and 150%, respectively. These effects were, to a large degree, reversible. Cytochalasins D and E produced greater increments in permeability for all molecules; this increase was only partially reversible. Ultrastructure analysis by scanning electron microscopy revealed extensive development of membrane protuberances (zeiotic knobs) on mesothelial cells exposed to cytochalasin B. A return to a normal apical cell surface was apparent although incomplete at 24 hr. Tight junctions were not grossly altered and major changes in intramembranous junctional strands were not observed. The major effect of cytochalasins on the cell surface may be responsible for the increased permeability to urea, predominately a transcellular probe. Inulin, which follows a paracellular route, was less affected. Altered protein permeability may be due to the action of cytochalasin on the exposed capillary endothelium in subdiaphragmatic areas where the mesothelium is discontinuous. PMID- 4039388 TI - [Surgical treatment of epithelial pilonidal cysts]. PMID- 4039389 TI - [Enuresis--symptom of delayed micturition development or an obstructive urinary tract anomaly?]. AB - In a review of the literature the question of origin of enuresis was studied. Most authors agree that diminished bladder capacity and involuntary detrusor contractions are the main cause of primary enuresis. Urodynamic investigations are necessary to differentiate developmental delay in bladder function form true anatomic infravesical obstruction. Therapeutic measures are successful in 2/3 of enuretics. Enuresis has a great tendency of spontaneous disappearance around 15% per year. PMID- 4039391 TI - Cellular retinol-binding protein: what is its role in vitamin A metabolism? PMID- 4039390 TI - [Sensitivity of mammalian tissues to prolonged exposure to high-tension permanent magnetic fields]. AB - The retinal epithelium, bone marrow and spermatogenic epithelium of mice exposed for 30 days to constant magnetic fields of 1.6 T were examined cytologically. During and after exposure the retinal and bone marrow epithelium showed no biologically significant deviations from normal. The mitotic changes were of small amplitude and insufficient to cause cell unbalance. No chromosome aberrations or degenerative changes in the cells were seen. In the spermatogenic epithelium the exposure to a constant magnetic field produced a destruction of mature cell elements. Due to this the total amount of spermatogenic cells was significantly lower during and immediately after exposure. PMID- 4039393 TI - Early language abilities of high-risk infants. AB - Ten children with a history of prematurity and respiratory distress syndrome (RDS) were matched with 10 full-term controls on the single-word stage of language. Eleven dependent variables probed for qualitative differences between the groups. Measures of receptive language were based on two assessment procedures specifically designed for this study. Expressive language measures were taken from a parent-elicited language sample. Control subjects demonstrated superior performance on all receptive language and child verbosity measures despite their younger age. PMID- 4039392 TI - Immunochemical studies on the localization and on the concentration of cellular retinol-binding protein in rat liver during perinatal development. AB - Studies were conducted to characterize the localization and the concentration of cellular retinol-binding protein (CRBP) in rat liver during perinatal development. The studies employed both a specific immunohistochemical staining procedure and a sensitive and specific radioimmunoassay for CRBP. Dramatic changes were seen in both the levels and localization of CRBP. Marked increases in hepatic CRBP levels were seen during the last week of gestation and the first postnatal week, resulting in a quadrupling of CRBP levels in this 2-week interval. During the second postnatal week CRBP levels remained very high (approximately 110 to 120 micrograms/gm of wet weight, with peak values at about day 11 of age). During the third postnatal week, CRBP levels declined, followed by a further decline to adult levels (40 to 50 micrograms/ml) postweaning. A changing pattern of immunohistochemical localization of CRBP was seen that correlated with the changes in CRBP levels. In fetal livers at days 11 to 13 of gestation, CRBP was selectively localized in perisinusoidal cells that resembled stellate (fat-storing) cells in their location and shape but that lacked the lipid droplets usually seen in these cells in adult liver. During the final week of fetal development and the first postnatal week, a progressive increase in CRBP in parenchymal cells was seen. By the second postnatal week, very strong staining for CRBP was seen in all parenchymal cells. The staining of parenchymal cells for CRBP then declined, and by weaning (day 21) the pattern of localization of CRBP in liver resembled that seen in the adult, with low to medium staining seen in parenchymal cells and strongly intense staining in perisinusoidal stellate cells. Thus, the rise and then decline in intensity of CRBP staining in parenchymal cells paralleled the pattern of changes seen in CRBP levels during the perinatal period. In the placenta, CRBP was selectively localized in the trophoblast layer of the chorioallantoic placenta and in the entodermal layer of the yolk sac placenta. These findings suggest that either retinol is metabolized or plays a functional role at these placental sites. PMID- 4039394 TI - Deuterium labelled steroid hormones: tracers for the measurement of androgen plasma clearance rates in women. AB - A method employing stable isotope-labelled tracers and gas chromatograph-mass spectrometry (GC-MS) analysis has been used to measure the plasma clearance rates (PCR's) of androstenedione (A) and testosterone (T) in normal women and women with androgen abnormalities including hirsutism and polycystic ovary syndrome. A solution of deuterium-labelled A and T is infused at a constant rate and blood samples taken at 2 and 2.25 h. Solvent extracts of the derived plasma samples, to which an internal standard has been added, are derivatized with pentafluoropropionic anhydride and the endogenous steroid and deuterated steroid are quantitated after an injection of the derivatization mixture into a capillary column GC-MS. The concentration of the deuterated steroid in the infusion mixture is measured and the PCR is calculated. In premenopausal normal women the PCRA is 1950 +/- 184 1/24 h (n = 5) and the PCRT is 484 +/- 82 1/24 h (n = 7). PMID- 4039395 TI - Studies of a plasma membrane steroid receptor in Xenopus oocytes using the synthetic progestin RU 486. AB - A steroid binding protein (Mr = 110,000) has previously been identified in the plasma membrane of Xenopus laevis oocytes by photoaffinity labeling with [3H]R5020. In order to further characterize this steroid receptor, the photoaffinity labeled receptor protein was solubilized with 0.1% Brij 35. The solubilized labeled receptor yielded an approximate mol. wt of 102,000 +/- 2,000 by sucrose density gradient centrifugation, suggesting that the solubilized receptor exists as a monomer. RU 486, a synthetic progestin antagonist for mammalian cytosolic receptor systems, inhibited up to 70% of [3H] R5020 photoaffinity binding to the 110,000-Dalton receptor with an IC50 of 5 microM and induced germinal vesicle breakdown (GVBD) with an EC50 of 9.0 +/- 0.6 microM. GVBD induced by RU 486 was slower than with progesterone, and RU 486 was less powerful than progesterone. Micromolar concentrations of RU 486 also potentiated GVBD induced by sub-optimal concentrations of progesterone or R5020. Furthermore, RU 486 inhibited oocyte plasma membrane adenylate cyclase with an apparent IC50 of 7.5 +/- 2.5 microM. The close correlation of the EC50 value for RU 486 induction of GVBD with the IC50 values for inhibition of [3H]R5020 photoaffinity labeling of the 110,000-Dalton receptor and inhibition of adenylate cyclase activity further supports the physiological significance of the oocyte plasma membrane steroid receptor. PMID- 4039396 TI - Adult respiratory distress syndrome in a pregnant patient with a pheochromocytoma. AB - Five weeks after developing spells of shortness of breath, headache, weakness and abdominal pain, a 29-year-old woman, who was in the 36th week of her third pregnancy developed adult respiratory distress syndrome (ARDS). Although the ARDS resolved after a cesarean section, her infant died at birth. Her "spells" continued until a left pheochromocytoma was diagnosed and resected 2 years later. If there are no other known inciting causes of ARDS in a pregnant patient, a pheochromocytoma should be ruled out with appropriate catecholamine determinations. PMID- 4039397 TI - Fifth annual meeting: American Society for Laser Medicine and Surgery. Orlando, Florida, May 27-29, 1985. PMID- 4039398 TI - The monochromatic green argon laser in the management of macular disorders. AB - The authors have been using an argon laser photocoagulator equipped with a green filter for about 21/2 years. Compared to the usual blue-green argon laser, the advantage of such an instrument is that green radiation is not absorbed to any significant degree by macular pigment. This ensures a selective action on hemoglobin and pigment epithelium. The green wavelength appears to be extremely useful in the management of macular disorders. The authors report the criteria they follow and the technique they use in the treatment of subretinal neovascular membranes and of macular edema arising from different retinal vascular disorders. PMID- 4039399 TI - Growth hormone in normal female rat plasma appears on gel filtration as a large molecular weight form. AB - Gel filtration of female rat plasma with normal growth hormone (GH) concentrations (less than 100 ng/m1) showed that nearly all the immuno-reactivity was centred on a peak with an apparent molecular weight in the region of 82,000. In contrast, pituitary GH was almost entirely monomeric. The majority of plasma prolactin (PRL) in the same samples had a molecular weight of 23,000 (i.e. monomeric), and was similar in profile to pituitary PRL. Samples from male rats showed some GH immunoreactivity at the 82,000 molecular weight position but more than 65% coeluted with monomeric PRL. In female plasma with GH concentration between 300 and 1,000 ng/ml, immuno-reactivity resolved into peaks at the void volume, the monomeric position, and a peak at 82,000 that decreased, as a percentage of the total, with increasing GH concentration. These results indicate the possible presence of a GH binding factor, with greater activity in female than male rat plasma. PMID- 4039400 TI - Tocopherol-phospholipid liposomes: maximum content and stability to serum proteins. AB - This study addresses two questions: 1) what is the maximum amount of tocopherol that can be contained in egg phosphatidylcholine liposomes, and 2) what is the stability of these vesicles in the presence of serum proteins? These liposomes, made with a French pressure cell, can contain no more than 33 mol% of tocopherol. Tocopherol changes liposomes in a manner similar to cholesterol, making them larger, less permeable to aqueous dyes and highly resistant to protein-induced disruption. The suppression of protein-induced disruption is more pronounced with tocopherol than with cholesterol, even at lower molar ratios. Thus, liposomes containing alpha tocopherol (15 to 30 mol%) may be useful for delivering physiological quantities of this vitamin to cells in culture or to tissue in vivo. PMID- 4039401 TI - Cholesterol precursors and their diurnal rhythm in lipoproteins of patients with jejuno-ileal bypass and ileal dysfunction. AB - Cholesterol synthesis and its diurnal variation was studied by measuring squalene, free and esterified methyl sterols and cholesterol, and triglycerides in serum lipoproteins every four hours over a period of 24 hours in controls and in patients with jejunoileal bypass or ileal exclusion. Fat absorption, as indicated by postprandial increase of very-low-density lipoprotein (VLDL) lipids (including chylomicrons) and fecal fat, was markedly impaired in jejunoileal bypass. Fecal analysis indicated that bile acid malabsorption enhanced cholesterol synthesis about sixfold in ileal dysfunction, and twofold in jejunoileal bypass with moderate bile acid and cholesterol malabsorption. The squalene contents were not increased consistently in the VLDL and combined low density plus high-density lipoproteins (LDL + HDL) of the two operated groups and, in contrast to the controls, the diurnal variation was inconsistent. The levels of unesterified methyl sterols, delta 8-dimethylsterol and delta 8 methostenol in particular, were several times higher throughout the 24 hour period in the lipoproteins of the two patient groups than of the controls, were higher in ileal dysfunction than jejunoileal bypass, exhibited a constant diurnal rhythm in the controls but only in the relatively small VLDL fraction (not in the large LDL + HDL) of the operated groups, and were positively correlated with cholesterol synthesis in the three groups combined (for methyl sterols in VLDL r = 0.740 and in LDL + HDL r = 0.869). Esterified methyl sterols were also increased in the operated groups but were not correlated with cholesterol synthesis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4039402 TI - Department of Public Health establishes review standards for new technologies. PMID- 4039403 TI - The role of cytoskeleton in the mechanisms of electric field effects and information transfer in cellular systems. AB - Microtubules and other cytoskeletal elements are ubiquitous components of all kinds of cellular systems. The suggestion is made that they are implicated in the mechanisms of biomedical and therapeutic field effects as well as in the processes of information transfer in neurons and other cells. Defined electrical properties and orientational field effects in microtubule systems are considered as a basis of such functions of the cytoskeleton. The concrete mechanisms of transfer of signals along the microtubules and other cytoskeletal fibres may involve cooperative periodical changes of conformation, of ion binding, or of different electrical parameters and enzymatic activities of their components. PMID- 4039404 TI - Effect of minor surgery on urinary flow and electrolyte excretion in the awake dog. AB - Spontaneous variations in urinary flow and electrolyte excretion are well known to occur both in man and in the non-human primate. Data on these spontaneous variations is scarce in the dog, an animal which is widely used in physiological investigations. Our study was designed to characterize the spontaneous pattern of renal hemodynamics, urine flow and electrolyte excretion in the awake dog both under conditions of minimal surgical stress (group I), and after routine preparatory surgery (group II). Our results show significant spontaneous variation for urine flow and urinary excretion of Na, K, Cl, HCO3, Ca, PO4 and Mg for both groups of dogs. Urinary excretion of Na, K, PO4 and Mg was significantly higher for group II than for group I (p less than 0.05). Glomerular filtration rate and effective renal plasma flow (estimated from the clearance of p aminohippurate) were measured in group II and showed no spontaneous variation. Our study shows that there is diurnal urinary electrolyte excretion variation in the dog which is exaggerated by small changes in the experimental protocol. These variations need to be considered when evaluating experimental maneuvers that induce changes in the renal handling of electrolytes in the dog. PMID- 4039405 TI - Tissue-specific inhibition of [3H]thymidine incorporation into DNA by carcinogenic N-nitrosamines. AB - The N-nitrosamines N-nitrosodimethylamine (DMN), N'-nitrosonornicotine (NNN) and 4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone (NNK) were injected intraperitoneally 24 h before sacrifice in F344 rats and C57BL mice in doses of 297 mumoles/kg b.w. and 148 mumoles/kg b.w., respectively. 2 h before sacrifice, the animals were given an intraperitoneal injection of [3H]thymidine. The results showed that the examined N-nitrosamines inhibited the incorporation of [3H]thymidine into DNA in a few tissues of the rats and the mice. The results indicated that the N-nitrosamines exerted a tissue-specific inhibition of the [3H]thymidine incorporation in the tissues reported to be involved in the biotransformation of these substances. The observed inhibitory effects on the incorporation of [3H]thymidine by DMN, NNN and NNK were also correlated to a considerable extent to the reported sites of carcinogenicity. The present study indicates that measurements of [3H]thymidine incorporation into DNA in various tissues of experimental animals is a useful short-term bioassay to evaluate the potential tissue-specific carcinogenicity of the N-nitrosamines. The method may also be useful as a complement to other short-term in vivo tests in the screening of potential genotoxicity of several other chemicals. PMID- 4039406 TI - Biosynthesis of two stage-specific membrane proteins during transformation of Plasmodium gallinaceum zygotes into ookinetes. AB - We have studied the synthesis and expression of surface proteins in zygotes of Plasmodium gallinaceum during their transformation to mature ookinetes. The cells were biosynthetically labelled in vitro using [35S]methionine and proteins were immunoprecipitated with rabbit anti-ookinete serum or monoclonal antibodies. Early zygotes (approx. 2 h post-gametogenesis and fertilization) synthesized and expressed on their surface a protein of Mr 26 000 as observed under reducing conditions on polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate (SDS-PAGE) (31 000 under non-reducing conditions) and continued to do so for 8-10 h; thereafter synthesis of the Mr 26 000 protein declined and little or none was synthesized in the mature ookinetes (greater than 20 h post gametogenesis). Between 3-5 h post-gametogenesis, zygotes also began to synthesize a protein of Mr 28 000 (34 000 under non-reducing conditions). Synthesis and expression of this surface protein continued throughout development; and the Mr 28 000 protein was the predominant surface protein synthesized by the mature ookinete. Mr 26 000 and Mr 28 000 proteins have been designated earlier as PgO-1 and PgO-2 respectively (Carter and Kaushal, Mol. Biochem. Parasitol. (1984) 13, 235-241). Neither protein was synthesized in the gametocytes prior to gametogenesis. Both proteins could be labelled with [3H]glucosamine or [3H]mannose. When zygotes were incubated with [3H]palmitic acid both PgO-1 and PgO-2 bound fatty acids in covalent linkage. The two proteins do not otherwise appear to be structurally related. They were differentially immunoprecipitated by different monoclonal antibodies and gave rise to distinct patterns of peptides following digestion with proteases such as Staphylococcus aureus V-8, trypsin and chymotrypsin. PMID- 4039407 TI - Evidence for the occurrence of respiratory electron transport in adult Brugia pahangi and Dipetalonema viteae. AB - Mixed-sex adult stages of Brugia pahangi and Dipetalonema viteae, in the absence of exogenous substrate, consumed oxygen at rates of 4.18 +/- 0.38 and 2.12 +/- 0.20 ngatoms O2 min-1 mg-1 dry wt. respectively. When calculated on a unit dry weight basis the endogenous O2 consumption rates (E-QO2) of mature adult male macrofilariae of B. pahangi and D. viteae were significantly greater than those of mature females, although the E-QO2 calculated per individual worm was essentially similar irrespective of sex. When assayed as separate unisexual groups, the oxygen uptake of male and female macrofilariae of both species was inhibited by classical inhibitors of respiratory electron transport (RET), and showed classical substrate bypass phenomena in response to succinate and ascorbate, N,N,N',N'-tetramethyl-p-phenylenediamine with respect to the RET inhibitors rotenone (inhibitor of complex I) and antimycin A (inhibitor of complex III). Since male worms elicited similar responses to the classical RET inhibitors as did mixed-sex and/or adult female populations, the possibility that developmental stages contained within the female filariids were contributing in any significant manner to the overall responses observed with the RET inhibitors can be discounted. Such responses as observed with live-intact macrofilariae are normally elicited only by mitochondrial preparations and suggest that the cuticles of both species are permeable to rotenone, succinate, antimycin A, N,N,N',N'-tetramethyl-p-phenylenediamine, azide and cyanide. The uncoupler 2,4 dinitrophenol stimulated the endogenous rate of oxygen consumption (E-QO2) of intact B. pahangi at 33-160 microM, indicating the probable occurrence of RET coupled oxidative phosphorylation. Higher concentrations of 2,4-dinitrophenol proved inhibitory. Respiratory studies on subcellular fractions substantiated the responses elicited by the intact parasites, suggesting the presence of antimycin A-sensitive and -insensitive RET pathways capable of utilising alpha glycerophosphate, succinate, and malate as substrates. Both B. pahangi and D. viteae macrofilariae therefore probably possess branched RET-pathways bifurcating on the substrate side of RET-complex III. The rates of substrate oxidation in terms of QO2 mg-1 mitochondrial protein compare well with those observed with other nematode parasites. PMID- 4039408 TI - Cryptosporidiosis in immunocompetent patients. AB - The intestinal protozoan cryptosporidium is known to cause diarrhea in immunocompromised patients, but few cases have been reported in detail in immunocompetent persons. During a 12-month period, we identified cryptosporidium in the stools of 43 immunocompetent patients. The numbers of cases were increased in those under 4 years old and in those from 30 to 39 years old. Of 30 index cases, 23 (77 per cent) were diagnosed in the late summer or the fall. Fifteen of the 43 patients (35 per cent) had other gastrointestinal pathogens, of which only Giardia lamblia was statistically associated with cryptosporidium. In the 28 patients in whom other gastrointestinal pathogens were not identified, the clinical manifestations were predominantly watery, nonbloody diarrhea and, less commonly, abdominal discomfort, anorexia, fever, nausea, and weight loss. The infection was self-limited in all 43 patients. Clustering of cases occurred in a day-care center and in two families. These clinical observations confirm worldwide findings and suggest that cryptosporidium is a relatively common nonviral cause of self-limited diarrhea in immunocompetent persons in the northeastern United States. PMID- 4039410 TI - Hypertensive hypertrophic cardiomyopathy. PMID- 4039409 TI - Studies of kidney and muscle biopsy specimens from identical twins discordant for type I diabetes mellitus. AB - To distinguish metabolic from genetic factors in the development of microangiopathy in diabetes, we evaluated biopsy specimens of kidney and quadriceps muscle from seven pairs of identical twins who were discordant for Type I (insulin-dependent) diabetes mellitus. Two of the diabetic patients had clinical diabetic nephropathy, including hypertension, marked albuminuria, and a substantially reduced creatinine clearance; the other five had normal renal function and only minor clinical indications of complications. All the twins of the diabetic patients had normal glomerular basement membrane widths and normal fractional volumes of the glomerular mesangium. Values for glomerular basement membrane width, tubular basement membrane width, and mesangial volume in each diabetic twin exceeded the values in the respective sibling (P less than or equal to 0.0035), even if the value in the diabetic twin lay within established normal ranges. Values for muscle capillary basement membrane width in the diabetic twins did not differ from those in their siblings (P = 0.5). Our observations suggest that the metabolic abnormalities of diabetes are necessary, if not sufficient, for the development of glomerular abnormalities. We also conclude that in diabetic patients, alterations in muscle capillary basement membrane width do not necessarily accompany pathologic lesions in the kidney. PMID- 4039411 TI - Isochromosome 9q in an infant exposed to ethanol prenatally. PMID- 4039412 TI - An animal model of Curvularia geniculata and its relationship with human disease. AB - The conidiospore of Curvularia geniculata was observed in the bronchial washings of a patient who subsequently developed pulmonary aspergillosis. Curvularia geniculata was grown in culture and used in experiments in mice to explore its possible role as a disease causing agent. The fungus, after intraperitoneal injection, produced granulomas in the liver and spleen. Studies on the pathogenicity of this fungus in mice produced similar lesions to those observed in the human case. A comparison of the lesions in the patient's lung and in the animal experimental model is presented. PMID- 4039413 TI - Thermodynamic compatibility of proteins in aqueous media. Part. I. Phase diagrams of some water--protein A--protein B systems. AB - The thermodynamic compatibility of proteins belonging to different classes according to Osborne has been investigated in aqueous media. Phase equilibrium for water--ovalbumin--soybean globulin fraction, water--ovalbumin--casein, water- casein--gliadin and water--casein--soybean globulin fraction systems has been investigated. The data obtained were analysed according to the theoretical concepts of Scott, Patterson and Prausnitz concerning the effect of polymer molar masses and the solvent quality on the phase equilibrium in similar systems. The analysis performed indicates that these concepts can be applied to the water- protein A--protein B systems. The phase equilibrium in water--protein A--protein B systems has some distinctive features as compared to that in systems containing two synthetic polymers in the single solvent. Firstly, proteins are usually compatible in a broader concentration range as compared to common polymers. Moreover, the separation of water--protein A--protein B systems into two phases often results in a considerable concentration of one of the protein components. Apparently, the latter fact can be associated with the marked difference in the interaction parameter of proteins belonging to different classes with the solvent, and, hence, with the marked difference in the hydrophilicity of the proteins investigated. PMID- 4039414 TI - Homoeo boxes and strings for the packaging of genes? PMID- 4039415 TI - Education policy and the heritability of educational attainment. AB - Many workers assume that genetically determined differences in intellectual ability will be influenced little by changes in educational policy or other environmental interventions. Others, however, have suggested that increasing equality of educational opportunity will lead to an increase in the heritability of educational attainment. The resolution of this issue has been delayed until now because of the extremely large sample sizes which would be required. Education data on twins and their parents, from the Norwegian twin panel, provide a unique opportunity to determine the impact on the heritability of educational attainment of the more liberal social and educational policies introduced in Norway after the Second World War. As reported here, for individuals born before 1940 there is a strong effect of family background on educational attainment, accounting for 47% of the variance, though genetic factors account for an additional 41% of the variance. For females born after 1940 and before 1961, the relative importance of genetic (38-45%) and familial environmental (41-50%) differences changes very little. For males born during the same period, the broad heritability of educational attainment has increased substantially (67-74%), and the environmental impact of family background has correspondingly decreased (8 10%). For males, at least, having well-educated parents no longer predicts educational success, as measured by duration of education, independent of the individual's own innate abilities. PMID- 4039416 TI - Unidirectional influx and phosphorylation of glucose analogues in cultured astroblasts. AB - Unidirectional influx of 14C-3OMG (3-O-methyl-D-glucose) and rate of phosphorylation of 14C-2DG (2-deoxy-D-glucose) were determined in primary cultures of astroblasts under conditions with negligible unstirred layers. The influx exhibited rate constants between 7.2 and 8.3 min-1 in the concentration range 2.5-25 mM of unlabeled 3OMG and was considered constant, irrespective of concentration of 3OMG. The rate of phosphorylation of 14C-2DG declined for rising concentrations of 2DG and hence showed saturability. The rate constants ranged from 7.9 to 0.1 min-1 in the concentration range 0.04-25 mM of 2DG. These results are not consistent with the view that the influx limits the rate of phosphorylation. They support the notion that the influx is not rate limiting for the phosphorylation. PMID- 4039417 TI - [A case of concomitant posterior fossa and supratentorial hemangioblastomas]. AB - The patient was a 31-year-old female who complained of headache and gait disturbance and admitted to our hospital on January 14, 1983. Familiar history revealed that her mother died of hemorrhage from hemangioblastoma in area postrema. Neurological examination revealed bilateral papilledema, right cerebellar sign and ataxia. Other neurological and clinical examinations were normal. CT-scan showed a right cystic cerebellar lesion and a right intraventricular lesion suggestive of hemangioblastomas. Right vertebral angiography demonstrated two vascular tumors lying in the right cerebellar hemisphere and right trigone of the lateral ventricle. Operation was performed on January 28, 1983. The histological diagnosis were hemangioblastomas. PMID- 4039418 TI - The interaction of the medial preoptic area and the dorsomedial-ventromedial nuclei of the hypothalamus in the regulation of the mating-induced release of prolactin. AB - The medial preoptic area (MPOA) and the dorsomedial-ventromedial nuclei (DMN-VMN) of the hypothalamus regulate the mating-induced nocturnal and diurnal surges of prolactin in rats. The neural mechanisms governing the release of the two surges differ. For the nocturnal surge the MPOA serves an inhibitory role while the DMN VMN serves a stimulatory role. The diurnal surge is controlled by both areas functioning as stimulatory centers. The goal of the present study was to explore the possibility of functional interactions between the MPOA and the DMN-VMN in control of mating-induced prolactin secretion. Stimulation of the MPOA in conscious, cervically stimulated (CS) females suppresses the nocturnal surge of prolactin. To determine if the inhibitory effects of the MPOA operate through the DMN-VMN, electrical stimulation was applied to the MPOA of conscious ovariectomized female rats bearing bilateral electrolytic lesions of the DMN-VMN. In the first experiment, control (sham-stimulated, sham-lesioned) CS females exhibited normal nocturnal surges which peaked at 03.00 h. MPOA stimulation (01.00-05.00 h) of both sham-lesioned and DMN-VMN lesioned CS females inhibited the release of their nocturnal surges. This suggests that the inhibitory function of the MPOA is independent of the DMN-VMN. MPOA stimulation can induce the release of a diurnal surge if the females are anesthetized with pentobarbital. In the second experiment, MPOA stimulation (15.00-19.00 h) of sham-lesioned anesthetized females produced elevated prolactin levels with significant peaks at 15.30 and 19.00 h. Anesthetized females with DMN-VMN lesions did not respond to MPOA stimulation with any change in prolactin secretion.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4039420 TI - Haloperidol in large doses reduces the cataleptic response and increases noradrenaline metabolism in the brain of the rat. AB - The neurochemical basis for the clinical observation that some patients receiving a large dose of haloperidol exhibit no extrapyramidal side effects was investigated in rats. Haloperidol at doses of 1, 2.5, 5, 7.5 and 10 mg/kg (i.p.) caused a dose-dependent decrease in the duration of catalepsy. Haloperidol at a dose of 10 mg/kg induced catalepsy lasting for only 20% of that obtained with 1 mg/kg. Haloperidol decreased the content of noradrenaline in the frontal cortex and thalamus in a dose-dependent manner, while the content of 3-methoxy-4 hydroxyphenylglycol (MHPG) showed a dose-dependent increase in the same areas of the brain. Thus, there was an inverse relationship between the duration of catalepsy and the ratio of 3-methoxy-4-hydroxyphenylglycol to noradrenaline in the frontal cortex or thalamus. The concomitant administration of 20 mg/kg of phenoxybenzamine with 10 mg/kg of haloperidol induced a long-lasting catalepsy. The result may indicate that the increased metabolism of noradrenaline by large doses of haloperidol was not secondary to the blocking of dopaminergic receptors. In contrast, haloperidol caused a dose-dependent decrease in the content of homovanillic acid and 3,4-dihydroxyphenylacetic acid in the striatum and mesolimbic area. These results indicate that noradrenergic hyperfunction in the frontal cortex or thalamus induced by large doses of haloperidol may reduce the cataleptogenic effect of the drug via indirect stimulation of a dopaminoceptive neuron in the striatum or mesolimbic area. PMID- 4039419 TI - Tolerance to some behavioural effects of lisuride, a dopamine receptor agonist, and reverse tolerance to others, after repeated administration. AB - To investigate whether prolonged pretreatment with the dopamine (DA) agonist lisuride would result in modification of some of its behavioural effects, food intake, locomotor activity, body temperature or stereotyped and mounting behaviour were evaluated after acute injections of different doses of lisuride into rats, pretreated daily for four weeks with either saline or lisuride. Rats pretreated with lisuride developed tolerance to its anorexigenic and hypothermic effects, and reverse tolerance to its effects on locomotor activity, stereotyped and mounting behaviour. Pretreatment with lisuride did not modify the activity of drug-metabolizing enzymes in the liver. These results, in addition to revealing the pattern of the changes in the behavioural effects of a DA agonist drug, after repeated administration, may be taken as evidence for the existence of different DA receptor systems in different areas of the brain, that mediate different behavioural effects, and that differ markedly in their reactions to prolonged stimulation with an agonist drug. PMID- 4039421 TI - Acremonium kiliense osteomyelitis of the calvarium. AB - A 35-year-old man with osteomyelitis of the calvarium, from which Acremonium kiliense was consistently isolated, was successfully treated with amphotericin-B and ketoconazole in addition to craniectomy. Subsequent acrylic cranioplasty produced a good cosmetic result. PMID- 4039422 TI - Effect of haloperidol and sulpiride on dopamine metabolism in nucleus accumbens and olfactory tubercle: a study by in vivo voltammetry. AB - Differential pulse voltammetry used with electrochemically pretreated carbon fibre microelectrodes enables separation between the two peaks corresponding to the ascorbic acid and catechol oxidation currents. The effects of haloperidol and sulpiride on the 3,4-dihydroxyphenylacetic acid peak recorded in the nucleus accumbens and olfactory tubercle of rats were studied. Chloral hydrate anaesthetized preparations and chronic preparations were used. A microdevice was designed to implant electrodes in freely moving rats. Voltammograms were recorded every minute in each structure in acute preparations and every 2 min in chronic preparations. In acute preparations haloperidol induced a similar dose-dependent increase in the catechol oxidation peak in both structures. Sulpiride at all doses only induced an increase in the olfactory tubercle. In chronic preparations haloperidol and sulpiride had even larger effects on the 3,4 dihydroxyphenylacetic acid peak in both regions. In these preparations sulpiride induced a significant increase in nucleus accumbens. The effects induced by haloperidol in the two regions were greater than those induced by sulpiride. The main conclusions of this study are that the results of voltammetry agree with biochemical results on the effects of haloperidol and sulpiride on dopamine metabolism. An interaction of chloral hydrate with the effects of the two neuroleptics was also observed. PMID- 4039423 TI - Regional and cellular differences in fucosylation of glycomacromolecules in the mouse brain. A biochemical and autoradiographic study of early postnatal and adolescent animals. AB - Mice of CBA strain of both sex were injected with [3H]fucose at age 2, 6, 12 or 30 days and the incorporation was determined biochemically 45, 90 and 180 min later. Biochemical measurements of the whole brain (at 90 min postinjection interval) revealed a stepwise age decrease in the amount of incorporated isotope (per mg protein). The amount of [3H]fucose available in the brain has however been found to decrease with age while the degree of its utilization increases. Thus, after correction of the data on [3H]fucose incorporation for the pool of the free isotope, a transient increase in fucosylation rate appeared at postnatal day 12 while the differences among 2-, 6- and 30-day-old animals became negligible. Further, the synthesis of fucosylated soluble glycomacromolecules appeared relatively higher at postnatal day 2 than in older age groups. Examination of different brain regions revealed that the rate of fucosylation is relatively highest in the olfactory bulbs; this prevalence starts appearing with age and becomes most evident in 30-day-old mice. Autoradiography carried out with 6- and 12-day-old animals revealed that the incorporation of [3H]fucose into meningovascular apparatus and the choroid plexus is a few times higher than into brain parenchyma. The regional differences appeared to be similar to those indicated by the biochemical data. Cellular analysis has shown that the incorporation is relatively higher in the cytoplasm of large projecting neurons of the cerebellum, hippocampus and the olfactory bulbs; in the latter region high amounts of macromolecule-bound [3H]fucose also appeared in the synaptic glomeruli.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4039424 TI - Activity, creatine kinase, and myoglobin in Duchenne muscular dystrophy: a clue to etiology? AB - Large and seemingly random fluctuations in the serum levels of creatine kinase (CK) and myoglobin (Mb) have been noted in patients with Duchenne muscular dystrophy. We studied seven affected boys, aged 2 to 9 years. Blood was drawn for CK and Mb every 4 hours, and the boys' activity was documented hourly for 4 days. There was a close correlation between serum levels of CK and Mb with physical activity. Fluctuations in serum levels of CK and Mb are not random and may result from an abnormality of fatty acid metabolism. PMID- 4039425 TI - [Aortic surgery and sexual function]. AB - An account is offered of the haemodynamic and neurological questions posed by the relation between reconstructive aortoiliac surgery and sexual function. Attention is drawn to the anatomical and surgical features of the preaortic sympathetic structures. In the light of experience gained in pelvic haemodynamic evaluation with the Doppler penile pressure index, a method that has proved very useful in the study of pre- and postoperative impotence in the arteriopathic subject, stress is laid on three conclusions: a) the high frequency of impotence in aortoiliac arteriopathy (65% in a personal series); b) the beneficial effect on penile circulation of revascularisation of the hypogastric artery (increase in pressure index in 70% of cases); c) the relatively high incidence of postoperative sexual disturbances (30% in the personal series) due to lesion of the preaortic sympathetic structures, the risk being greater with techniques requiring wide exposure of the aorta. This danger is foreseeable in all sexually potent patients and should determine the indication for surgery, the method chosen (extra-peritoneal route, extra-anatomical by-pass), and the technique (in an aorto-femoral by-pass, the aorta should be prepared in accordance with carefully followed rules of surgical anatomy, and confined wherever possible to a short infrarenal segment). PMID- 4039426 TI - The control exerted by the substantia nigra on the quiet biting attack elicited by hypothalamic stimulation in the cat. AB - The effects of substantia nigra (SN) (pars compacta) stimulation on the quiet biting attack evoked by hypothalamic activation in the cat were studied. The measure of the aggressive behavior was the latency of the biting which did not greatly change from one animal to another when hypothalamic stimulation was performed with the same parameters. Concurrent activation of the SN determined an inhibitory effect on the studied behavior in the form of an increase in the biting latency or loss of the attack pattern. The inhibitory role of the SN on predatory attack behavior is discussed. PMID- 4039427 TI - Increase of self-mutilation behavior in forelimb deafferented rats, following stimulation of the dorsal raphe nucleus. AB - The role of dorsal raphe nucleus (DRN) was studied in rats which develop scratching or/and self-mutilation after deafferentation of brachial plexus. The extent of the lesions was measured in four groups of deafferented rats. Two control groups: implanted and not implanted, a group of animals in which DRN was stimulated, and a group in which it was electrolytically destroyed. We observed an increase of scratching and self-mutilation in the implanted group but overall in the stimulated group, and no change in the abnormal behavior was provoked by DRN lesion. PMID- 4039428 TI - Blind, olfactory bulbectomized female rats do not have daily luteinizing hormone surges. AB - Previous studies from other laboratories have shown that female hamsters on short photoperiod become acyclic and have daily LH surges. These effects are eliminated if the animals are pinealectomized (PX) before being placed on the short photoperiod. Reiter and colleagues have shown that pre-pubertally blinded (BL) and olfactory bulbectomized (BX) female rats also have irregular estrous cycles, and this effect is also eliminated by PX [Endocr. Rev., 1 (1983) 109]. The main question addressed by the present study was whether the BL + BX rats also have daily LH surges. Twenty-five-day-old female Sprague-Dawley rats were divided into 5 groups: LD 14:10 sham (control); BL + BX; BL + BX + PX; LD 6:18 sham; and LD 6:18 BX. Ten weeks following surgery, all animals were sampled (0.5 ml) every 5 h for 2 days from an indwelling atrial catheter. Daily vaginal smears indicated that the BL + BX group were in estrus much less frequently than controls (15.8 +/ 1.8 vs 27.3 +/- 1.5% of days cornified cells, 10 rats/group smeared for more than 23 days each) and in general had longer, irregular cycles. The other 3 groups all had smear patterns similar to controls. All 5 groups had LH surges on the day of proestrus (greater than 200 ng/ml maximum value), but no group had LH surges on 2 sequential days or an LH surge on any other day of the cycle.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4039429 TI - [Immunodepressive effect of cell populations with varying erythropoietic activity in embryos and newborn mice]. AB - The cells of liver from the 11-12 day old embryos and of spleen from newborn mice were transplanted to adult syngeneic recipients immunized by the ram erythrocytes. The immune response in the recipient spleens was estimated by the number of antibody-forming cells. The cells of embryonic liver and of newborn spleen suppressed the immune response in recipients to a great extent. The immunodepressive effect obtained was similar to suppression due to the transfer of cell populations from the mice in which erythropoiesis was stimulated by hypoxia of phenylhydrazine. The splenocytes of adult control mice and the cells of spleen from 6-9 day old mice did not exert such an effect. The rabbit antiserum to erythroid cells relieved the suppressor effect of the embryonic liver and neonatal spleen cells, as well as of the other erythropoietic populations. A conclusion is drawn on participation of cells-suppressors of the erythroid nature in the mechanisms of immunological non-responsiveness at the early ontogenetic stages in mice. PMID- 4039430 TI - [Regulating role of the microtubule system in the distribution of actin microfilament bundles in embryonic fibroblasts]. AB - The effect of colcemid on the distribution of actin microfilament bundles in the mouse embryo fibroblasts was studied using immunomorphological methods. In the control fibroblasts, microfilament bundles usually cross the entire cell and are oriented in parallel to the stable edges of the cell. In the colcemid-treated cells there are several groups of bundles. In each group all bundles are oriented in the same direction but these directions do not depend on the cell shape. Besides, bundles in the colcemid-treated cells are shorter than in the control cells. Microtubules are suggested to control the organization of action bundles. PMID- 4039431 TI - [Effect of certain factors on sheep oocyte maturation when cultured within intact follicles]. AB - The effect of the medium composition and cultivation time on the maturation of sheep oocytes cultivated in vitro within the intact follicles was studied. The highest incidence of maturation was observed in medium 199 with 20% of sheep serum taken from an animal on the 16th day of the sexual cycle in a gaseous mixture of the following composition: 5% O2, 5% CO2, 90% N2 during 24 hrs. PMID- 4039432 TI - Visual loss following panretinal photocoagulation for proliferative diabetic retinopathy. AB - We reviewed the preoperative, postoperative, and follow-up examinations, fundus photographs, and fluorescein angiograms of 175 eyes of 134 patients with proliferative diabetic retinopathy treated with panretinal photocoagulation. Forty-four (25%) of these eyes lost two or more lines of vision by the time of the last follow-up examination. Follow-ups ranged from 3 to 48 months, with a median follow-up of 15 months. The most common cause of decreased visual acuity was chronic macular edema that had developed following laser treatment, occurring in 14 (8%) eyes. The causes of visual loss following panretinal photocoagulation are discussed. PMID- 4039433 TI - Comparative treatment trial of augmentin versus cefaclor for acute otitis media with effusion. AB - A total of 150 children with acute otitis media were randomly allocated to treatment with amoxicillin-potassium clavulanate (Augmentin) or with cefaclor. Each drug was given in a daily dosage of approximately 40 mg/kg in three divided doses for ten days. Tympanocentesis done before treatment yielded specimens that contained pneumococcus or Haemophilus sp or both in 67% of specimens. Viridans group streptococci were isolated from 10% of specimens and Branhamella catarrhalis from 6%. Patients were scheduled for follow-up examinations at midtreatment, end of therapy, and at 30, 60, and 90 days. Of the 150 children, 130 were evaluable. Five of 60 patients (8%) treated with cefaclor were considered therapeutic failures because of persistent purulent drainage and isolation of the original pathogen or suprainfection. There were no failures among patients treated with Augmentin (P = .019). Rates of relapse, recurrent acute otitis media with effusion, and persistent middle ear effusion were comparable in the two groups of patients. Diaper rash, or loose stools, or both were significantly more common in children treated with Augmentin (34%) than in those taking cefaclor (12%), but in no case was it necessary to discontinue medication because of these mild side effects (P = .002). Cefaclor therapy was discontinued in one patient because of severe abdominal pain and vomiting. In this study, treatment with Augmentin was superior to treatment with cefaclor in the acute phase of acute otitis media with effusion, but Augmentin produced more adverse effects. The rates of persistent middle ear effusion and recurrent acute otitis media with effusion were comparable with the two regimens. PMID- 4039434 TI - [Functional state of the testicles in various forms of retardation of sexual development in boys]. PMID- 4039435 TI - [Bone marrow culture in patients treated with Ticlopidine]. AB - Bone marrow cells obtained from 15 patients treated with Ticlopidine (500 mg/day) for a month, and from 20 matched controls were cultured in agar. GM colonies and clusters were counted after 7 and 14 days of culture. CFU GM were slightly decreased in the patients treated by Ticlopidine. In 8 patients, in which the bone marrow was cultured on a second occasion 3 months latter, a slight increase in the inhibition of CFU GM was observed. It could be due to the mechanism of action of the drug (by an increased synthesis of PGE1) and not to a toxic side effect. The few cases of reversible agranulocytosis reported in the literature might be due to the inhibition of myelopoiesis in patients with medullary reserves already impaired. PMID- 4039436 TI - Radioactive iodine-125 implantation for cancer of the prostate. AB - Localized cancer of the prostate can be treated by radical prostatectomy, external beam irradiation, or radioactive implantation with similar survival results. Radical prostatectomy, however, almost universally results in impotency, although a new, nerve-sparing procedure may preserve potency in B1 patients. External beam irradiation radiates a large volume of tissue with significant rectal and bladder morbidity, 23-47% risk of impotency, and requires prolonged treatment (6-8 weeks). Radioactive implantation may be done suprapubically or transperineally using iodine-125, gold-198, or radon-222 permanent implantation techniques and iridium-192 or radium-226 removable implantation techniques. Interstitial iodine-125 implantation is frequently employed since it is a short procedure and limits the morbidity to a 7% incidence of impotency, 20% urinary complications, and 5% rectal complications. The overall 5-year survival of patients with iodine-125 is 79%, the survival rate decreasing with increasing T or N stage or increasing grade of tumor. PMID- 4039437 TI - Spontaneous rupture of the uterus associated with pyometra. AB - A case is reported in which an elderly patient was admitted with signs and symptoms of an acute abdomen. A laparotomy revealed uterine rupture with free pus in the peritoneal cavity and subsequent histology of the uterus showed no evidence of malignancy. PMID- 4039438 TI - Behavior and growth parameters of large white turkeys as affected by floor space and beak trimming. II. Females. AB - The effects of floor space allowance and beak trimming on behavior and growth performance of female Large White turkeys were studied. Floor space allowances were 5.6, 7.0, and 9.3 dm2/bird from 0 to 8 weeks of age and 14.0, 18.6, and 23.2 dm2/bird from 8 to 16 weeks of age. Floor space was adjusted by changing pen size to assure a constant number of birds per pen. Results showed that neither floor space allowance nor beak trimming had any significant effect of any of the variables under study through 8 weeks of age. At 16 weeks of age, growth, feed consumption, feed efficiency, feather scores, live market quality grades, and mortality were still unaffected. Beak trimming significantly reduced body weight gain, body weight, and feed consumption but had no significant effect on feed efficiency, feather scores, or mortality. Agonistic (aggressive) behavior was very low in this population of females. Of significance, however, were the nonaggressive behaviors of social "pecking" and "pecking and pulling" of feathers. Feather-pecking activity was unaffected by previous or subsequent floor space allowances through 16 weeks of age; however, the incidence of pecking and pulling of feathers was highest among females previously assigned the largest floor space allowance (9.3 dm2/bird) in the brooder house and subsequently allowed the smallest floor space allowance (14.0 dm2/bird) in the grower house. Beak trimming significantly increased the frequency of both "pecking" and "pecking and pulling" of feathers over that of their untrimmed contemporaries when the females were 12 and 16 weeks of age. Possible reasons for this are discussed. PMID- 4039439 TI - Effects of chronic high-level manganese exposure on male behavior in the Japanese quail (Coturnix coturnix japonica). AB - Male Japanese quail were chronically exposed to 5000 ppm manganese (Mn) as particulate manganese oxide (Mn3O4) in their diet from hatching to 75 days of age. No decrements in growth or in other indices of general toxicity were noted. There were significant (P less than .05) age-related increases in general locomotor activity in the control group, although no significant (.05 less than P less than .10) increases were seen in the Mn-treated group. Both control and Mn treated groups had significant (P less than .05) age-related increases in aggressive behavior with an overall significant (P less than .05) treatment related depression. Serum testosterone concentration was only slightly depressed (.05 less than P less than .01) in the 75 day-old, Mn-treated quail. Both the control and Mn-treated quail had higher liver Mn concentrations than previously reported in rodents. Both control and Mn-exposed quail accumulated 5 to 10 times more Mn in their livers than similarly treated rodents. This study indicated that the Japanese quail was less sensitive to particulate Mn3O4 exposure than rodents treated comparably. PMID- 4039440 TI - The effect of maternal age on broiler performance on litter and a raised perforated floor. AB - The effect of maternal age and floor type on the performance of broiler chicks was studied. Hatching eggs were collected and hatched from the same Cobb commercial strain of broiler breeder hens at 27, 42, and 52 weeks of age. Chicks from each group were reared separately or intermingled on commercial diets. Maternal age had a significant effect (P less than .05) on live body weights of broilers reared either separately or intermingled. Weight differences found at day-old between chicks from 42- and 52-week-old dams were overcome by the age of 44 days. Chicks from the 27-week-old dams were not as heavy and consumed less feed than those from other parentage groups. Broilers on the perforated floors were heavier than their floor counterparts. Overall performance, except for body weight, was not affected by floor type or rearing condition. PMID- 4039441 TI - Disruption of estrous cycles in exercise-trained rats. AB - The female Sprague-Dawley rat was evaluated as an animal model for the menstrual irregularities that are common in women athletes. Daily vaginal smears revealed that estrous cycles were markedly disrupted in rats during a 10-week exercise training program, while cycles remained normal in sedentary rats. Compared to 9 sedentary rats, the 10 exercise-trained rats had longer mean cycle lengths and fewer estrus smears. Six of the exercise-trained rats, but none of the sedentary rats, had an "anestrus period" with more than twice the normal interval between estrus smears; one exercise-trained rat became essentially acyclic. Weight gain during the 10-week training program was lower in exercise-trained rats than in sedentary rats. Colonic temperatures, monitored at rest and during 30 min of exercise, were slightly lower in exercise-trained rats with irregular estrous cycles than in exercise-trained rats with regular cycles, indicating that unusually elevated body temperatures during exercise are not responsible for exercise-related reproductive acyclicity. It is concluded that the female Sprague Dawley rat may be a useful animal model for the study of menstrual irregularities associated with exercise training. PMID- 4039442 TI - Medaka eggs as a model system for screening potential teratogens. PMID- 4039443 TI - A comparison of the DNA intercalative binding of bay versus K region metabolites of benzo[a]pyrene. AB - The DNA intercalating properties of trans-7,8-dihydroxy-7,8-dihydrobenzo[a]pyrene (1) and of trans-4,5-dihydroxy-4,5-dihydrobenzo[a]pyrene (2) have been compared in UV absorption and in fluorescence emission and fluorescence lifetime studies. Molecules 1 and 2 represent steric models of the two epoxide containing metabolites of benzo[a]pyrene, trans-7,8-dihydroxy-anti-9,10-epoxy-7,8,9,10 tetrahydrobenzo[a]pyrene (BPDE) and benzo[a]pyrene-4,5-oxide. The former of these metabolites is a highly carcinogenic bay region metabolite, the latter is a much less carcinogenic K region metabolite. The association constant for intercalation for model 1 is 5,226 M-1. This is more than 2.7 times greater than that for molecule 2. These results taken together with results form previous studies of bay and K region metabolite models of benz[a]anthracene suggest that intercalation is important to the overall carcinogenic activity of polycyclic aromatic hydrocarbons. PMID- 4039444 TI - A molecular model relating to carcinogenesis. PMID- 4039445 TI - Properties of human neuroblastoma cells following induction by retinoic acid. PMID- 4039446 TI - Radiosensitivity of neuroblastoma. PMID- 4039447 TI - Therapeutic application of radiolabelled monoclonal antibody UJ13A in children with disseminated neuroblastoma--a phase 1 study. PMID- 4039448 TI - Sequential cis-platinum and VM26 in neuroblastoma: laboratory and clinical (OPEC regimen) studies. PMID- 4039449 TI - Modifications in adrenal hormones response to ethanol by prior ethanol dependence. AB - Ethanol was administered to rats by means of a liquid diet for 16 days; after an ethanol-free interval of four weeks, animals received a test (IP) dose of ethanol (2 g/kg), and the adrenocortical and adrenomedullary responses were evaluated. Chronically ethanol-exposed animals showed tolerance to the stimulatory effect of ethanol in the pituitary-adrenal axis. Likewise, previously dependent rats showed tolerance to the increase in the activity of the adrenomedullary function induced by acute administration of the drug. Our results indicate that chronic ethanol ingestion can induce persistent changes after complete alcohol abstinence. PMID- 4039450 TI - Dose-related effects of pentobarbital on the genetic differences seen between paired, Roman high- or low-avoidance rats in a shuttle box. AB - The effects of low doses of pentobarbital (PB) were measured on the activity levels, shock-induced fighting and avoidance or escape behavior of paired rats of two psychogenetically-selected lines, in multiple shuttle box sessions, following shock-induced fighting or two-way avoidance training. Each pair served as its own control, by receiving drug injections only every second week. Independent of training conditions, the RLA/Verh pairs showed about 90% freezing behavior and no fighting, whereas all RHA/Verh pairs preferred avoidance or escape behavior to fighting. Although their intertrial (shuttling) responses (ITRs) were reduced at the higher doses of PB used, RHA/Verh rats were still capable of most behavioral responses even at 24 mg/kg, whereas all RLA/Verh rats slept at that dose. On the other hand, the ITRs and avoidance responses of the (less active) RLA/Verh rats were increased by injections of 8 and 16 mg/kg PB. The results, especially those pertaining to freezing behavior and changes in activity levels, were discussed in comparison to other selected rat strains which have shown certain similarities to the Roman lines in regard to "emotionality" and associated neurochemical status. PMID- 4039451 TI - Comparative behavioral effects of CNS cholinesterase inhibitors. AB - Phenylmethanesulfonyl fluoride, methanesulfonyl fluoride, and physostigmine were compared on the efficacy with which each could suppress methylphenidate-induced stereotyped gnawing, an extrapyramidal motor behavior. Whereas physostigmine produced powerful suppression of the stereotypy, the sulfonyl fluorides did not produce any clear behavioral effect. Biochemical experiments conducted with the behavioral tests demonstrated that the sulfonyl fluorides produced inhibition of whole brain, caudate, cortex, cerebellum, hippocampus and brain stem cholinesterate equal to that produced by physostigmine. The reason for the marked discrepancy between the behavioral effect of physostigmine and the sulfonyl fluorides is unknown. It is, however, clear that the effect of the various drugs on extrapyramidal motor behaviors is not a simple function of the degree to which each inhibited CNS cholinesterase. PMID- 4039452 TI - Cold-restraint stress and urinary endogenous beta-phenylethylamine excretion in rats. AB - Stress applied to humans increases the urinary excretion of the endogenous amphetamine-like substance beta-phenylethylamine (PEA), a potentially common mediator of amphetamine and stress effects. The present study was conducted to determine if cold-restraint stress in the rat could represent an animal model for stress-induced changes in PEA disposition in humans. The stressor markedly elevated the urinary excretion of endogenous PEA in a manner that was not attributable to changes in urinary pH, glomerular filtration rate or in food consumption. In addition, a large diurnal variation in PEA excretion was noted. The data suggest that the variables responsible for stress-induced alterations in endogenous PEA disposition in humans and rats are generally similar. However, they also indicate that in rats, in contrast to humans, PEA disposition is subject to diurnal changes. PMID- 4039453 TI - Phencyclidine-like effect of cyclazocine on pentylentetrazol-induced seizures in laboratory animals. AB - The present work deals with an EEG and behavioural study of the effect of cyclazocine against the convulsions due to pentylentetrazol (PTZ) in mice, rats and rabbits. In rats, cyclazocine, at the high doses (15-25 mg/kg) prevents the tonic motor convulsions and EEG epileptiform "grand mal" seizure induced by PTZ. In rabbits and mice, cyclazocine inhibits the tonic motor convulsions without modifying either the spike-frequency or the duration of the PTZ-induced EEG seizures. Naloxone, even at high doses, was not able to block the anticonvulsive effects of cyclazocine on PTZ-induced convulsions in the rat. The effects of cyclazocine were compared to those of phencyclidine. These results confirm the multiple behavioural effects of cyclazocine and support the idea that both cyclazocine and phencyclidine, may act on the PCP/sigma receptor identified in binding studies. PMID- 4039454 TI - Interactions of cis-platinum with cellular zinc and copper in rat liver and kidney tissues. AB - In the present study the effects of cis-diamminedichloroplatinum II (cis-DDP) on tissue and subcellular concentrations of endogenous Zn and Cu was investigated in liver and kidneys of rats injected i.p. with 5 mg/kg of cis-DDP. The binding of Pt to cytosolic ligands and its effect on Zn and Cu binding was also investigated. cis-DDP significantly reduced cellular Zn (20%) and Cu (23%) levels particularly in the kidneys. Intracellularly, these decreases were largely reflected in the corresponding cytosolic fractions, with 64% decrease in Zn and 56% in Cu concentrations. At 24 h following cis-DDP injection, in both liver and kidneys, about 50% of cytosolic Pt was present as low molecular weight (LMW) species and the remainder as protein-bound. A small proportion of cellular Pt was bound to a metallothionein-like protein in the liver as well as the kidneys. The binding of renal Zn to cytosolic proteins and LMW Zn-binding ligands was significantly decreased by cis-DDP. In the liver cytosol, there was a marked redistribution of Zn and Cu from LMW Zn/Cu-binding ligand to the MT-like proteins. PMID- 4039455 TI - The premenstrual syndrome and its relationship to accidents. PMID- 4039456 TI - [Value of ECG-gated cardio-computed tomography (cardio-CT) for diagnosis of hypertrophic cardiomyopathy--a comparison with angiocardiography]. PMID- 4039457 TI - [Diagnosis, incidence and course of nonpuerperal mastitis]. AB - The clinic of radiology at the university of Graz has examined 158 cases of nonpuerperal mastitis. By means of mammography and during further clinical course, differentiation to the inflammatory carcinoma was possible. In 55% of the examined cases one ore more clinical symptoms, which are described as typical for the nonpuerperal mastitis, were absent. With the help of mammography in most of all cases an exact diagnosis was made. PMID- 4039458 TI - 24-hour cerebrospinal fluid levels of vasopressin in hydrocephalic patients. AB - The variation in vasopressin concentrations of ventricular cerebrospinal fluid and plasma throughout a 24-h period was studied in 10 patients with hydrocephalus. In 6 control patients, the diurnal variation in plasma vasopressin concentrations was studied. Vasopressin concentrations were determined by radioimmunoassay in plasma and in extracted and unextracted cerebrospinal fluid. Cortisol and osmolality in plasma were also measured. Vasopressin concentrations measured in extracted cerebrospinal fluid showed only small intra- and interindividual variation, while the corresponding values for unextracted cerebrospinal fluid were 2-5-fold higher and showed more variation. Plasma vasopressin concentrations varied considerably throughout the 24-h period in the individual hydrocephalic patient and between the patients. The pattern of variation was inconstant with no circadian rhythm, and the variation was not related to any changes in plasma osmolality, blood pressure or intracranial pressure. In some of the patients, the normal diurnal pattern of variation in plasma cortisol was broken, however, without a relation to the observed fluctuations in vasopressin concentrations. The abnormal variation of plasma vasopressin and cortisol was considered to reflect stress in connection with the intracranial pressure monitoring procedure. In the control patients, plasma vasopressin showed only small variations and plasma cortisol showed a normal diurnal rhythm. It is concluded that cerebrospinal fluid vasopressin concentration in patients with hydrocephalus is very constant throughout the day, even when plasma vasopressin concentrations show marked episodic increases. Thus, a circadian rhythm in the cerebrospinal fluid vasopressin concentration, as reported in several animal species, could not be confirmed in these patients. PMID- 4039459 TI - Further characterization of the endogenous natriuretic and digoxin-like immunoreacting activities in human urine: effects of changes in sodium intake. AB - In the present study natriuretic activity and digoxin-like immunoreacting activity (DLIA) were determined in small molecular weight (MW) fractions of urine from healthy subjects during low (35 mmol/day) and high (greater than 400 mmol/day) sodium intake by bioassay and by a radioimmunoassay for digoxin, respectively. After gel filtration of urine on a Sephadex G-25 column the natriuretic activity appeared in the post-salt fraction SIV, whereas DLIA was present in small amounts in the salt fraction SIII and, with consistently higher activity, in the post-salt fraction SIV. Natriuretic activity significantly increased and DLIA decreased in fraction SIV with high sodium intake, but total urinary excretion of DLIA remained unaltered during changes in sodium intake. In addition, anion-exchange and reverse-phase chromatography revealed that DLIA is not specifically related to the natriuretic activity but also reflects unspecific binding of various urine constituents to this digoxin antibody. Although the antibody binds a natriuretic material, this radioimmunoassay is thus unsuitable to determine the endogenous natriuretic activity in urine fractions. Whereas they elute differently on reverse-phase chromatography, amino acid analyses revealed that both the natriuretic factor directly purified from the post-salt fraction SIV and the natriuretic material bound to the digoxin antibody have in common four amino acids at similar molar ratios. The physicochemical properties as evidenced by chromatographic and electrophoretic studies as well as enzymatic inactivation suggest that the low MW natriuretic factor(s) in human urine may be associated with a small peptide(s) of weak acidic nature. PMID- 4039460 TI - The effect of beta-adrenoceptor blockade and of thromboxane synthetase inhibition, alone and in combination, on arrhythmias resulting from myocardial ischemia. AB - The effects of pretreatment with metoprolol (2 mg/kg, i.v.), UK 38,485 (5 mg/kg, i.v.), and a combination of the two drugs were examined on early (0-0.5/hr) and late (0.5-4 hr) ischemic arrhythmias resulting from coronary artery ligation in the anesthetized rat. Metoprolol was administered at different times after the onset of ischemia to determine any relationship between antiarrhythmic effects and the time of administration. Studies with two other thromboxane synthetase inhibitors, dazoxiben and carboxyheptylimizadole, and a thromboxane analogue, U 46,619, were performed on the early arrhythmias to investigate a possible role of thromboxane A2 in the genesis of ischemic arrhythmias. Pretreatment and very early intervention with metoprolol caused a significant reduction in the incidence of ventricular fibrillation (VF) in the 0-0.5 hr period. The number of ventricular ectopic beats (VEBs) and the incidence of ventricular tachycardia (VT) during the 0.5-4 hr period were markedly reduced by both pretreatment and late intervention with metoprolol. VEBs and VT in the 0-0.5 hr phase were reduced by UK 38,485 and carboxyheptylimidazole and increased by U 46,619. Administration of a combination of the drugs produced a significant reduction in early VF and late VEBs. PMID- 4039461 TI - Endotoxin-induced acute renal failure in mice. Effects of indomethacin and the thromboxane-synthetase antagonist UK 38.485. AB - Functional acute renal failure (ARF) was induced within 24 h following i.p. injection of 200 micrograms E. coli endotoxins (ET) into C3H/HeHan mice. Pre- and post-treatment with either UK 38.485, a selective thromboxane (TX)-synthetase inhibitor, or with the cyclo-oxigenase inhibitor, indomethacin (IM), does not prevent acute renal failure in these mice. Histologically, only very little fibrin degradation and few microthrombi are present 24 h later in the kidneys, so that disseminated intravascular coagulation (DIC) mechanisms cannot have caused the significant azotemia. Slight histological changes are accentuated in the UK 38.485-treated group. Only the indomethacin group has a significantly increased mortality as compared to all other groups. We conclude from our study that with low dosages of endotoxins functional ARF can be induced in mice without a circulatory shock and early mortality and that both UK 38.485 and IM are of little value in preventing it. PMID- 4039462 TI - [Heptaminol adenosine phosphate and the premenstrual syndrome]. AB - The efficacy of the adenosine phosphate of heptaminol on the functional symptomatology of the premenstrual syndrome has been assessed in the framework of an "open" controlled trial against a reference product. 45 women received adenosine phosphate of heptaminol (6 gelatine capsules/day) or the reference product during 2 cycles. The statistical analysis of the results by symptom demonstrates the markedly superior activity of the adenosine phosphate of heptaminol on pelvic pains (p less than 0.02), and on the pains and heaviness of the lower limbs (p less than 0.05). The superiority of adenosine phosphate of heptaminol was similarly demonstrated in the global evaluation of results. The tolerance must be regarded as excellent. PMID- 4039463 TI - Diagnostic value of prealbumin and retinol-binding protein in acute and chronic liver diseases. AB - Prealbumin (PA) and retinol-binding protein (RBP) serum concentrations have been determined in 161 patients with different chronic and acute liver diseases and in 49 healthy controls. Their possible role in clinical practice as liver markers of hepatic biosynthesis in comparison with other traditional tests: albumin, pseudocholinesterase and clotting factors II, VII and X associated activity (Hepato-Quick) was investigated. PA and RBP were always highly intercorrelated and significantly decreased in acute viral hepatitis, steatosis, chronic persistent and active hepatitis, cirrhosis, hepatic tumors and primary biliary cirrhosis. Among the different tests, PA and RBP presented the best values of specificity (0.98 and 0.97, respectively), sensitivity (0.77 and 0.73) and positive (0.99) and negative prediction (0.57 and 0.46). In chronic liver diseases PA and RBP distinguished more efficiently than the other biosynthetic markers among diseases with different degree of severity. In acute viral hepatitis the behavior of PA and RBP, followed for 4 consecutive weeks, was similar to that of Hepato-Quick and better than the other tests in reflecting the clinical course of the disease. PMID- 4039464 TI - [Clinical studies of follicle formation in the bovine ovary]. PMID- 4039465 TI - Transfection of v-rasH DNA into MCF-7 human breast cancer cells bypasses dependence on estrogen for tumorigenicity. AB - The natural history of estrogen-responsive breast cancers often involves a phenotypic change to an estrogen-unresponsive, more aggressive tumor. The human breast cancer cell line, MCF-7, which requires estradiol for tumor formation in vivo and shows growth stimulation in response to estradiol in vitro, is a model for hormone-responsive tumors. The v-rasH onc gene was transfected into MCF-7 cells. The cloned MCF-7ras transfectants, which expressed the v-rasH messenger RNA and v-rasH p21 protein (21,000 daltons), were characterized. In contrast to the parental cell line, MCF-7ras cells no longer responded to exogenous estrogen in culture and their growth was minimally inhibited by exogenous antiestrogens. When tested in the nude mouse, the MCF-7ras cells were fully tumorigenic in the absence of estrogen supplementation. Thus, cells acquiring an activated onc gene can bypass the hormonal regulatory signals that trigger the neoplastic growth of a human breast cancer cell line. PMID- 4039466 TI - Circulating autoantibodies to the 200,000-dalton protein of neurofilaments in the serum of healthy individuals. AB - There is substantial evidence that human serum contains antibodies to many autoantigens. For example, all healthy people have autoantibodies (immunoglobulin M) to some undefined brain antigens. In this study immunoblots and immunohistochemical staining were used to detect antibodies to neural tissues in serum samples from 200 healthy people and 200 patients with various neurological diseases. Ninety-nine percent of the 400 subjects had serum immunoglobulin M and 95 percent had immunoglobulin G that bound to a 200-kilodalton protein in homogenates of neural tissues. In most cases there were no antibodies to anything else in the homogenates. The 200-kilodalton protein was the heaviest of the neurofilament triplet proteins. These observations do not support a role for antibodies to the 200-kilodalton protein of neurofilaments in the pathogenesis of neurological diseases. PMID- 4039467 TI - Evaluation of danazol influence upon the uterus using scanning electron microscopic morphometric and biochemical analyses. AB - A study using a Sprague-Dawley rat model was designed to correlate morphologic and intracellular steroid receptor alteration with danazol therapy. One uterine horn was removed for cytoplasmic estrogen receptor analysis following four to eight days of danazol therapy. This was followed by intra-aortic injection of buffered phosphate solution and 3 per cent glutaraldehyde. The remaining uterine horn was removed for scanning electron microscopic and morphometric analysis of light microscopic changes. After four days of treatment, there was an increase in the nuclear to cytoplasmic ratio compared with that of the control tissue. Vaginal smears on the eighth day of danazol exposure indicated that the rats had entered a noncycling estrus state, and there was a significant increase in the estrogen-specific binding capacity of the endometrial cells. Scanning electron microscopy showed a distinct decrease in endometrial folds, microvilli and glandular openings, which suggests a decline in secretory activity in the danazol treated group. Thus, danazol induced measurable changes in the estrogen binding capacity of endometrial cells, and these changes correlated with certain morphologic alterations in the endometrial lining. PMID- 4039469 TI - [CO2-laser treatment of condylomata acuminata. Current clinical aspects]. PMID- 4039468 TI - Experimental design considerations: a determinant of acute neonatal toxicity. AB - Few studies have investigated the potential developmental differences resulting from treating neonatal rat pups in either split-litter or whole-litter (nested) experimental designs. We directly compared rat pups dosed with triethyl lead (TEL) via both split-litter (representing all dosage groups within a single litter) and nested (all pups randomly assigned to a single litter receive the same dose) designs. The nested design was chosen to produce a uniform behavioral pattern across pups within each litter, whereas the split-litter design was chosen to promote pup competition and differential maternal care. On postpartum day 5, pups were administered either 12, 13, 14, or 15 mg/kg TEL, with each design represented by 12 litters. Although the LD50 values for the two designs were not significantly different, there were significantly more deaths in the 12 mg/kg dosage group within the split-litter design than in the nested design group. Preweaning survival times for split-litter dosed animals were also decreased. In addition, significant growth reduction (7-16%) was observed in the split-litter group, relative to the nested design animals during the preweaning period. These results suggest that neonatal toxicity is not independent from experimental design considerations, and that the factors of littermate competition and/or pup-induced maternal care deserve further study. PMID- 4039470 TI - [Vulvitis]. PMID- 4039471 TI - Release of plasminogen activator from isolated perfused dog heart. AB - The release and the local activity of plasminogen activator (PA) were studied in isolated perfused dog hearts, without or with intimal injury induced by means of a balloon catheter inserted into the left anterior descending coronary artery (LAD). Thrombin but not DFP-thrombin induced a dose-dependent PA release in doses of 8 to 32 units. ADP 20 or 200 mumol but not ergonovine 20 or 200 micrograms induced a weak PA release. The local PA activity was much lower in the LAD at 1 or 4 weeks after this injury than in the intact LAD. However, the release of PA from the hearts after intimal injury was similar to findings in the intact hearts. We conclude from this study that thrombin plays an important role in regulating the coagulation-fibrinolysis system in endothelial cells and that changes in the properties of the endothelial cells may lead to initiation and enhancement of atherosclerosis. PMID- 4039472 TI - A collaborative study of a proposed international standard for tissue plasminogen activator (t-PA). AB - An international collaborative study involving seven laboratories was undertaken to assess which of three lyophilised preparations might serve as an International Standard (I.S.) for tissue plasminogen activator (t-PA). Two of the preparations were isolates from human melanoma cell cultures while one was of pig heart origin. A clot lysis assay was used by all participants in the study. The data suggested that both preparations of human cell origin were comparable, in that their log dose-response lines were parallel, while that of the porcine preparation was not. Accelerated degradation studies indicated that one melanoma extract (denoted 83/517) was more stable than the other and it was decided to recommend preparation 83/517 as the standard for t-PA. The International Committee for Thrombosis and Haemostasis (Stockholm 1983) has recommended the use of this material as a standard and it has been established by the Expert Committee on Biological Standardization of the World Health Organization as the International Standard for tissue plasminogen activator, with an assigned potency of 1000 International Units per ampoule. PMID- 4039473 TI - Elevated plasma fibronectin during venous occlusion. PMID- 4039474 TI - Formation of stable complexes between urokinase and a human urinary component. AB - Human urine was found to contain multiple species of urokinase (UK)-like plasminogen activator (PA) activity when subjected to concentration and/or dialysis and analyzed by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and zymography. Untreated, freshly voided urine contained only Mr = 52,000 and 35,000 UK while dialyzed or undialyzed urine concentrates contained additional PA activity at Mr = 80,000 and 95,000. SDS-PAGE of incubation mixtures of radioiodinated UK (Mr = 52,000 or 35,000) and urine concentrates revealed the presence of radiolabeled complexes with Mrs of 80,000 and 95,000. The bond(s) involved in complex formation was also relatively resistant to heat and reduction. Treatment of radioiodinated UK with the serine proteinase inhibitor, p-nitrophenyl guanidinobenzoate, prior to incubation with dialyzed, concentrated urine prevented formation of the complexes. In addition, the enzymatic activity of the Mr = 80,000 and 95,000 species was unaffected by diisopropyl fluorophosphate. These results indicate that UK forms SDS-stable complexes with a urinary component that has a Mr of approximately 40,000. The results further suggest that these complexes express PA activity when analyzed by SDS-PAGE and zymography. PMID- 4039475 TI - ADP induced depolarization of human platelet membrane potential. AB - The transmembrane potential of human blood platelets suspended in plasma was investigated by studying the distribution of a radiolabeled permeant ion [14C] thiocyanate. The membrane potential of resting platelets was found to be -54.50 mV +/- 9.23 S.D. with a range of -39 to -76 mV (n = 27). The possibility that platelet activation alters membrane potential or that changes in membrane potential serve as an activation trigger was investigated. Stimulation by ADP (10 microM) resulted in a significant (p less than 0.05) depolarization of the membrane potential. Preincubation with 6 mM EGTA failed to inhibit ADP-induced depolarization even though EGTA effectively prevented primary and secondary aggregation but not shape change. Preincubation with PGE1 inhibited shape change, aggregation, and the ADP-induced depolarization. No significant change in membrane potential was observed following stimulation by epinephrine (50 microM). These results suggest that the initial interaction of ADP and its receptor may involve an inward positive current which can be determined by thiocyanate distribution. PMID- 4039476 TI - [Congenital hydrocephalus, oligophrenia, dwarfism, centripetal obesity and hypogonadism; an X-linked recessive hereditary illness?]. AB - Two male patients from one family are reported, who are affected with congenital hydrocephalus, mental retardation, short stature, obesity and hypogenitalism. Most probably the mode of inheritance is X-linked recessive. PMID- 4039477 TI - Lack of severe malformations versus occurrence of marked embryotoxic effects after treatment of pregnant mice with cis-platinum. AB - The embryotoxic and teratogenic effects caused by the inorganic cytostatic drug cis-diamminedichloroplatinum(II) ("cis-platinum") were investigated in mice. Single doses of 2.5, 5, 10 or 20 mg cis-platinum/kg were administered to pregnant mice on day 8, 10, 12, 14 or 16 of pregnancy; on day 18, all fetuses were removed and examined for toxic phenomena and for external, skeletal and internal malformations. A dose-dependent reduction of the number of fetuses per litter, a decrease of fetal body weight, and a marked retardation of skeletal ossification processes reflected the severe embryolethal and embryotoxic influence of cis platinum; this influence was most pronounced when the drug was applied during organogenesis, i.e. on day 8, 10 or 12 of murine pregnancy. In contrast, the incidence of malformations was surprisingly rare after treatment with cis platinum: Neither external nor skeletal malformations appeared more frequently than in control populations; most fetal internal organs were without anomalies, however, a portion of 10-20% of the fetuses exhibited slight signs of hydrocephaly after application of cis-platinum on day 12. PMID- 4039478 TI - Capillary permeability-increasing enzyme from the venom of Agkistrodon caliginosus (kankoku-mamushi): activity due to the release of peptide material from a protein in bovine plasma. AB - When a mixture of the purified capillary permeability-increasing enzyme from A. caliginosus venom and bovine plasma or heated bovine plasma was injected into the depilated skin of the back of a rabbit, the capillary permeability-increasing activity was much greater than that induced by injection of the enzyme alone. The substance which increases capillary permeability was extracted from the incubated mixture of bovine plasma and enzyme with 50-70% ethanol. Its activity was lost when treated with carboxypeptidase A. Thus, it is supposed that the increase in capillary permeability induced by the enzyme is due to a low molecular weight peptide released from a protein in bovine plasma by the action of the enzyme. No liberation by the enzyme of histamine or anaphylatoxins of the complement system was found. PMID- 4039479 TI - Effect of the anticarcinogenic drug 6-mercaptopurine on mineral metabolism in the mouse. AB - The effect of 6-mercaptopurine (6-MP) on mineral metabolism was investigated in mice. C57BL mice were given 6-MP for 5 consecutive days. Treatments were: no injection; saline; vehicle injection (carboxymethylcellulose (CMC]; 5 mg/kg 6-MP; 25 mg/kg 6-MP; 50 mg/kg 6-MP; 100 mg/kg 6-MP; and 150 mg/kg 6-MP. After the 5-day period, tissues were removed and the levels of calcium (Ca), magnesium (Mg), zinc (Zn), copper (Cn) and manganese (Mn) were measured. In liver, but not in intestine or kidney, zinc and calcium levels increased in a dose-dependent manner. The weight of the stomach relative to body weight was significantly greater in mice receiving 100 mg/kg and 150 mg/kg BW doses of 6-MP than in those given lower doses, despite significantly lower body weight. This result indicated that 6-MP produced gastric toxicity. Injection of saline or vehicle had no effect on any of the parameters measured. The effect of 6-MP on mineral changes and on stomach-emptying may be partly responsible for at least some of its negative side effects. PMID- 4039480 TI - A study of the personal meaning of suicide in the context of Baechler's typology. AB - This study investigates suicide from the vantage point of the suicidal person by analyzing the personal meaning(s) of the act for the individual. Twenty-seven suicidal persons and survivors contributed to the research. Their individual recollections are studied and ordered within the framework of Jean Baechler's approach (as presented in his book Suicides). The study indicates that there is, in each case, an identifiable purpose or a pattern of purposes that can be categorized within a restricted and meaningful system, which may help the observer understand what human beings are doing when they want to end their lives. PMID- 4039481 TI - The behaviour of Homo sapiens, the forgotten factor in the transmission of tropical disease. AB - The behaviour of the pathogens responsible for tropical disease and the behaviour of the hosts other than man are both studied in great detail, but the behaviour of man, the third component in these cycles of transmission, is for the most part totally and inexplicably disregarded. Even when the pathogens are actively brought to us through the agency of an arthropod host, we too often ease the passage of the vectors either by unthinkingly providing facilities for their breeding or by neglecting the simple steps that can be taken to prevent their feeding on us. The problem resolves itself into two parts, (i) the collection and collation of relevant data on human behaviour, and (ii) the taking of steps to change this behaviour. Part two has recently been greatly facilitated by the development of radio transmission via artificial satellite. While WHO is now making a start on both these aspects it is doing so at a relatively low level. Instead, the two phases of this new approach should be given top priority even if it means large scale reorganization of relevant university departments and even of WHO itself. We have, after all, had almost 100 years to try out the old methods and, as far as the Third World is concerned, they have for the most part failed. PMID- 4039482 TI - Mastitis in rural Gambian mothers and the protection of the breast by milk antimicrobial factors. AB - Mastitis was found to be a sizeable clinical problem in a group of lactating Gambian mothers. The mean monthly incidence was 2.6% and repeated episodes of mastitis were common. The role of milk antimicrobial factors in the local defence of the breast against mastitis was investigated by analysis of IgA, IgG, IgM, C3, C4, lactoferrin and lysozyme in the breast milk of 10 mastitis patients. Acute inflammation of the breast was accompanied by the rapid appearance of high concentrations of serum-derived immunoproteins in mastitic milk. Changes in the milk levels of lactose, sodium and transferrin indicated that this was due to a temporary opening of the paracellular pathway. Concentrations of secretory immunoproteins (IgA, lactoferrin and lysozyme) exhibited a delayed response, being elevated one week after the attack of mastitis. The normal milk of mastitis sufferers was significantly deficient in IgA, C3 and lactoferrin when compared with other lactating women suggesting that the former were predisposed to mastitis. PMID- 4039483 TI - [Scanning electron microscopy of the cytoskeleton of the aortic endothelial cells of mature and aged rats]. AB - The aortic endothelial cells' cytoskeleton was visualized using scanning electron microscopy of detergent-extracted cells. It is shown that the aortic endothelial cells' cytoskeleton undergoes structurization during aging. The cytoskeleton structurization is supposed to be an adaptive reaction which increases stability of intracellular contacts and cell adhesion with the underlying substrate. PMID- 4039484 TI - Pathophysiology of lower urinary tract dysfunction. AB - Lower urinary tract dysfunction can be considered in terms of two broad categories: problems caused by abnormalities of the filling and storage phase and problems related to the voiding phase. The author prefaces this discussion with a review of normal anatomy and physiology. PMID- 4039485 TI - Urodynamics of the female lower urinary tract. AB - The symptoms associated with voiding disorders and incontinence in female patients are notoriously misleading. Even experienced urodynamicists are unable to achieve a 50 per cent success rate for predictive diagnosis based on symptoms and physical examination in any group except pure stress incontinence. Urodynamic studies are an essential part of the investigative sequence required to make an accurate diagnosis. If this is not made, then treatment will be empirical and the success of therapy correspondingly disappointing. The advent of urodynamic investigations has allowed a more rational approach to treatment with documented improvement in the success of therapy. However, our precise understanding of the pathophysiology of incontinence and voiding disorders remains incomplete. Nevertheless, a systematic scheme of investigation using standardized record keeping and urodynamic techniques allows an accurate diagnosis in most patients. It is essential that additional testing should be performed when the urodynamic investigations fail to explain the patient's complaints. It is hoped that advanced techniques and in particular the electrophysiologic approach may provide the explanation for phenomena as yet ill-understood, such as bladder instability. This article has outlined the importance of a thorough basic assessment of each female patient with a symptomatic inquiry guided by urodynamic insight and a careful physical examination. The basic techniques of flow studies, cystometry, both filling and voiding, and urethral profilometry were described, and the more complex and difficult electrophysiologic tests were outlined. PMID- 4039486 TI - Resting and stress urethral pressures as a clinical guide to the mechanism of continence in the female patient. AB - Urethral closure pressures are examined with respect to continence and aging. An attempt is made to interpret the inherent orientation sensitivity of microtip transducer profilometry. The transmission of cough pressures along the length of the urethra is also examined, showing that incontinence is associated with low transmission. PMID- 4039487 TI - The pathophysiology of stress incontinence. AB - The factors contributing to stress incontinence of urine are reviewed and categorized with respect to their effects on coaptation and compression of the urethra. Intrinsic urethral dysfunction and poor anatomic support are discussed from both a functional and a pathophysiologic approach. PMID- 4039489 TI - [Chronic arterial hypertension in children with corrected obstructive uropathy]. AB - Chronic hypertension in children with obstructive uropathy perhaps is an infrequent, but not unimportant condition. In patients with bilateral obstruction often accompanied by urinary tract infection, hypertension may develop in spite of restoration of urinary flow. Hypertension in these patients is caused by parenchymal damage of one or both kidneys resulting as a late sequela of obstruction even after normalisation of urinary flow. This report deals with three cases of this type of obstructive uropathy and severe hypertension. Hypertension developed up to 6 years after normalisation of urinary flow. In the two patients, in who serum renin examinations were performed, high renin levels were determined peripherally (6.2-7.9 ng/ml/h) and in both kidney veins (8.5-34.7 ng/ml/h). Early diagnosis and treatment of hypertension may have important implications for the outcome of these patients. In all patients glomerular filtration rate was diminished (31.6-67.8 ml/min X 1.73 m2), in two of them further deterioration during the observation period of 3-4 years could be avoided. PMID- 4039488 TI - Comparison of the cytotoxic activities of chemotherapeutic drugs using a human bladder cancer cell line. AB - Many chemotherapeutic drugs have been used to treat patients with advanced bladder cancer, but few of these have been evaluated adequately in phase II clinical trials. Continuous cell lines provide one means for comparing the in vitro cytotoxicities of anticancer agents. In this study, a continuous cell line derived from a transitional cell cancer of the human bladder, which still produces tumours histologically similar to the tumour of origin on xenotransplantation, was used to measure the in vitro cytotoxicities of twelve chemotherapeutic drugs by clonogenic assay. The most cytotoxic agents tested were methotrexate, mitoxantrone, adriamycin, mitomycin C and cisplatin. These in vitro findings are compatible with the activity of these drugs given systemically as single agents in phase II clinical trials in patients with advanced bladder cancer. PMID- 4039490 TI - [Multifocal hemangioma of the bladder. A problem in pediatric neurology]. AB - Bladder hemangiomas mainly become manifest before the tenth year of life. A report of a multiple, infiltratively growing, capillary hemangioma of the urinary bladder with obstructive uropathy in an 11-year-old boy. The technical problems of diagnostic and surgical endoscopy through the urethra in children are discussed. The importance of a form of supravesical urinary diversion satisfactory to the child (uretero-sigmoidostomy) after cystectomy is emphasized. PMID- 4039491 TI - [Paul Mellin and the international reflux study in children]. PMID- 4039492 TI - [Dilated upper urinary tract. Evaluation of the obstructive relevance of the ureteral junction by intrapelvic pressure-flow measurement (Whitaker test) in 23 children]. AB - Twenty-three children with equivocal uretero pelvic junction (UPJ)-obstruction underwent antegrade pressure flow studies. In three of the twelve children with upper urinary tract dilatation without vesicorenal reflux UPJ-obstruction could be excluded. Voiding cystograms showed vesicorenal reflux in eleven of the children with reflux induced hydronephrosis in seven cases. The coexistence of UPJ-obstruction and vesicorenal reflux has been noted in four children. In 23 pressure flow studies there was only one equivocal result. Twelve kidneys said to be obstructed were operated and the diagnosis was confirmed. The uneventful follow-up in the other ten children confirms the diagnosis of hydronephrosis without obstruction. The overall accuracy rate of the Whitaker-test was 96%. PMID- 4039493 TI - [Value of anatomic and functional obstruction of the urethra of girls in enuresis, recurrent urinary tract infections and reflux]. AB - Enuresis, recurrent urinary tract infection and vesico-ureteral reflux in 157 girls between 4 months and 11 years of age were the reasons for urological examination including calibration of urethra and urodynamic evaluation. Meatal stenosis or distal urethral stenosis was found in 14% measured by bougie a boule calibration. Functional disorders of the lower urinary tract were found in 47.8%. While anatomical stenosis requires surgical intervention functional infravesical obstruction is treated by biofeedback procedures. Functional infravesical obstruction is found much more often than anatomical stenosis. PMID- 4039494 TI - [Compensatory hypertrophy of the healthy kidney as an important prerequisite for nephrectomy of the small kidney]. AB - In children with hypertension and unilateral small kidney blood pressure may be normalized by nephrectomy of the small kidney; but hypertension may persist, if the contralateral kidney is not normal. Nephrectomy of the small kidney therefore should only be performed, if integrity of the contralateral kidney is certain. The best indicator about integrity in our experience is the ability of the contralateral kidney to develop compensatory hypertrophy. Compensatory hypertrophy is easy to determine, one or two urograms with clearly visible outlines are needed. If compensatory hypertrophy cannot be proven, nephrectomy of the small kidney is contraindicated. Case reports illustrate the importance of the determination of compensatory hypertrophy of the contralateral kidney for making such decisions. PMID- 4039495 TI - [Hypertension caused by reflux nephropathy--normotension following bilateral partial nephrectomy]. AB - Hypertension in childhood is often due to refluxnephropathy. In case of segmental lesion of the kidney hypertension may be curable by partial nephrectomy. We report on a girl with bilateral lesions and hypertension. The patient became normotensive without medication after bilateral upper pole partial nephrectomy. PMID- 4039496 TI - [Results of operative therapy of double kidney]. AB - 107 patients were submitted to operative treatment of a duplex kidney from 1968 to 1980. In 62 kidneys of children heminephrectomy was performed and in 26 parenchymapreserving operations like ureterocystoneostomies (n = 17) and pyelopyelostomies (n = 9) were done. Fever and urinary tract infection was seen more often in patients submitted to partial ureterectomy than after total ureterectomy. Long time follow-up (medium 8.8 years) was available in 33% of the children. Two non-functioning renal units after heminephrectomy and one recurrent vesicoureteral reflux were documented. Renal length was determined by planimetry. While values within the +/- 2SD range were seen after antireflux surgery and after pyelopyelostomies growth of the kidneys after heminephrectomy seemed to be hampered. Although renal hypoplasia and dysplasia is seen in a lot of duplex kidneys, heminephrectomy should not be done routinely. Preoperative planimetry of the kidney gives information about the amount of parenchyma most probably lost by heminephrectomy. In addition malfunction of the contralateral "good" kidney should be suspected, if compensatory hypertrophy of this kidney does not develop in spite of a grossly scarred contralateral kidney. PMID- 4039497 TI - [Operative therapy in boys with posterior urethral valves. How much is sensible?]. AB - From 1976 to 1983 23 boys with posterior urethral valves were seen. Two boys died during early infancy from terminal renal failure. One boy is submitted to a chronic peritoneal dialysis program. Of the remaining 20 patients ten show signs of compensated renal failure (creatinine greater than 1.5 mg/dl), ten boys show normal renal function. Four out of 46 kidneys were removed. Vesicoureteral reflux was primarily present in 14 renal units (30.4%). Three of these kidneys were removed. Reflux ceased spontaneously after valve ablation in ten renal units, ureterocystoneostomy was done in one. Ureterovesical obstruction was seen in three renal units and treated by resection and neoimplantation. Renal hypoplasia and -dysplasia together with urinary tract infections determine the degree of renal function impairment in boys with posterior urethral valves. Surgical intervention of the upper urinary tract is seldom needed. Antenatal diagnosis of obstructive uropathy is helpful to avoid septic obstruction in the neonate. Percutaneous nephrostomy is the treatment of choice in critically ill children presenting with dilatation of the upper tracts. PMID- 4039499 TI - Transmission of infection and multidose syringes. PMID- 4039498 TI - [Children with posterior urethral valves, dilatation of both ureters and chronic kidney insufficiency. A retrospective analysis of effectiveness and risk of operative measures]. AB - In all 16 boys with posterior urethral obstruction, bilateral ureteral dilatation and chronic renal failure (serum creatinine above 2 mg/dl), who were seen during the last 12 years in our departments, data about time and outcome of urological therapeutic interventions (nephrectomy, relief of bladder outflow obstruction and ureter reimplantation) were analysed retrospectively. In five patients surgical treatment was performed in our hospital, the other 11 children were referred from other hospitals. Nephrectomy of a small but not functionless kidney was performed in three of four patients without proper indication. Bladder outflow obstruction was relieved too late in five patients and insufficiently in four. 36 ureter reimplantations were performed on 24 ureters in 14 patients; reimplantation was unsuccessful in 26 ureters (72%) either because of postoperative reflux (11 ureters) or because of postoperative obstruction (15 ureters). In our opinion in boys with posterior urethral valves and bilateral ureteral dilatation ureter reimplantation should be limited to patients with proven obstruction at the uretero-vesical junction. PMID- 4039500 TI - Causes of lamb mortality in a commercial lowland sheep flock. PMID- 4039501 TI - Oestrus control in the ferret. PMID- 4039502 TI - Mastitis in sheep in Iraq. PMID- 4039503 TI - Reduced superovulatory response in the ewe following repeated gonadotrophin treatment. AB - Thirty-nine pure bred Texel ewes were superovulated with horse anterior pituitary extract (HAP) and 24 of these ewes were treated for superovulation a second time 55 to 76 days after the first treatment. A 12 day SC-9880 sponge was used to synchronise oestrus in the ewes and all were superovulated with 200 mg HAP (4 days X 50 mg HAP). Surgical insemination and cervical insemination were employed to breed the ewes following the first and second superovulation treatments, respectively. The incidence of oestrus and ewes ovulating were significantly (P less than 0.005) lower following the second treatment. There was no significant difference in the ovulation rate in ewes ovulating between the first and second treatments. The mean number of eggs recovered per ewe decreased following the second treatment but fertilisation rate was not affected. Results would suggest that the period of time between first and second superovulation treatments was not sufficiently long to allow Texel ewes to respond to a second stimulation, or that surgical insemination may have had a detrimental effect. PMID- 4039504 TI - [Outlook for the programmed insemination of sheep in the anestrual season]. AB - Studied were certain methods for programming the estrus and fixing the optimal term for the insemination of sheep. A record was kept of the changes taking place in the genital apparatus in various periods of time following the use of hormonal preparations during the anestral period. The fertility of sheep was also taken into consideration both after the first treatment with serum gonadotropin and after the two-fold programmed insemination at a 16-day interval with regard to the total fertility. It was shown that the optimal time for programmed insemination of sheep was between the 36th and the 56th hour after the three-fold injection with Prolosan at 12-hour intervals so far as periods other than the breeding season were concerned. Fertility at two-fold injection rated at 121 per cent, and conception--at 78.2 per cent. PMID- 4039505 TI - [Prediction of the periods favorable for the development of gastrointestinal nematodes in sheep in various climatic regions of Bulgaria]. AB - Bioclimatogrammes have been worked out for the various regions of the country to foretell the periods during which the microclimatic conditions in them favour the development of the preparasitic forms of gastrointestinal nematodes of sheep in the environment. It was found that best for the worms of the Heamonchus genus were the conditions in the May-June period, and in some regions in July too. There were in individual climatic regions conditions that were best in the months of September and October. The preparasitic forms of nematodes of the Ostertagia and Trichostrongylus genera could develop throughout the pastures in almost all climatic regions of the country during the April-July period with a month prior to and after this term as well as during the October November period. PMID- 4039506 TI - [Use of monoclonal antibodies in the diagnosis of fibrinolysis]. AB - Monoclonal antibodies to tissue type plasminogen activator (t-PA), urokinase (u PA) and alpha-2-antiplasmin were obtained by immunizing Balb C mice with the respective purified antigens and fusion of spleen cells with mouse myeloma cells (NSO). The selected monoclonal antibodies reacted exclusively with the respective antigens used for immunization. 3 out of 7 monoclonal antibodies directed against t-PA inhibited plasminogen activation by t-PA and 6 of 7 interfered with the fibrin potentiating effect. Only one out of 5 monoclonal antibodies directed against u-PA inhibited plasminogen activation by u-PA. None of the monoclonal antibodies directed against t-PA or u-PA inhibited the cleavage of low molecular weight paranitroanilide substrates by the respective plasminogen activators. Likewise, the 3 monoclonal antibodies to alpha-2-antiplasmin did not functionally inhibit alpha-2-antiplasmin. The selected monoclonal antibodies were used to develop sensitive test systems for the respective antigens. The lower detection limit for determination of t-PA was found to be 0.5 ng/ml, for determination of u PA 0.05 ng/ml, and for determination of alpha-2-antiplasmin 5 ng/ml. PMID- 4039507 TI - [Procaine as a biologically active substance--its effects on the uterus mucosa and tongue epithelium of rats]. PMID- 4039508 TI - [Ultrastructure of adrenal cortex glomerular and fascicular zones following long term administration of ethanol in the rat]. PMID- 4039509 TI - Electron microscopic study of the overlapping effect of thyrotropin and gonadotropins on the Leydig cells of 15-day old chick embryo. PMID- 4039510 TI - Egg yolk immunoglobulin Y as an alternative antibody in the serology of echinococcosis. PMID- 4039511 TI - Simultaneous Kawasaki disease in identical twins: case report. PMID- 4039512 TI - Long-term reproduction in mouse populations of different origin. PMID- 4039513 TI - [Guidelines for data on experimental animals and their care based on results of animal experiments. Committee for the Biological Characterization of Experimental Animals/GV-SOLAS]. PMID- 4039515 TI - [Proposal for the treatment of Syphacia muris infection in the laboratory rat with the agent pyrvinium pamoate]. PMID- 4039514 TI - [Lactation inhibition with various dosages of lisuride--prolactin secretion and effectiveness]. AB - The influence of lisuride in three several dosages (600, 750, and 900 micrograms) was studied on prolactin secretion and inhibition of lactation in 30 normal postpartum patients. 10 normal nursing postpartum patients served as controls. A rebound effect of prolactin secretion was demonstrable following lisuride medication during 10 days. This effect did not occur after a therapy lasting 15 days. 600 micrograms of lisuride daily showed a good inhibition of lactation and suppression of prolactin secretion. Severe side effects could be only observed during lisuride treatment with a dosage of 900 micrograms. PMID- 4039516 TI - [Clinico-pathogenetic correlations in intellectual deficiency in premature infants]. AB - The comparison of 32 immature infants with mental retardation of various degree (based on the results of clinical, immunological and biochemical examinations) with full-term infants with analogous pathology showed in the former group a high incidence (82.8%) of cerebral antibodies to antigens of the homo- and heterological brain in the complement consumption test. Therapeutic measures helped to reduce neuroimmune changes while the presence of antibodies to the homologous brain remained stable. Using data on the excretion of vanillyl amygdalic and homovanillic acids, the authors established alterations in catecholamine catabolism as well as in the activity of serum amine oxidase, which depended on the degree of mental retardation. Changes in individual components of catecholamine metabolism were found to correlate with neuroimmune shifts. The data obtained point to the presence of changes in biogenic amine metabolism and in immunological processes in mentally retarded children, which are very likely to be caused by immaturity at birth. PMID- 4039517 TI - Diurnal fluctuations of human nerve conduction velocity. AB - In 14 normal subjects, sensory conduction velocity (SCV), determined at constant skin temperature, displayed diurnal fluctuations which were related to similar variations in rectal temperature. Control of surface limb temperature in routine EMG does not completely obviate the variations induced by the body temperature cycle. Diurnal fluctuations should be taken into account when performing serial CV determinations in the same individual. PMID- 4039518 TI - The role of microfilaments in the healing of the corneal endothelium. AB - Actin microfilaments are presumed to play a role in cell locomotion. The function of these filaments may be selectively suppressed by cytochalasin. A dose dependent delay of the repair of a corneal endothelial defect by the application of cytochalasin in tissue culture has been observed by SEM. This observation confirms that the actin microfilaments are important for the endothelial repair. PMID- 4039519 TI - Rates of synthesis of prealbumin and retinol-binding protein during acute inflammation in the rat. AB - The rates of synthesis of prealbumin (PA), retinol-binding protein (RBP), and other plasma proteins were measured in primary monolayer cultures of rat hepatocytes isolated from normal rats and from rats 18 h after induction of an inflammatory reaction by subcutaneous injection of croton oil. The inflammatory pattern of protein synthesis seemed to persist in the isolated hepatocytes for 1 2 days. This pattern included significantly decreased rates of synthesis of PA. The rate of synthesis of RBP was probably also decreased, but significantly less than the rate of PA synthesis. The results support the idea that it is mainly the decreased rate of PA synthesis which is responsible for the decreased plasma concentration of PA, and its ligand RBP and retinol during inflammation. PMID- 4039520 TI - Torque-velocity relations in the quadriceps muscle of smoking-discordant twins with different fibre type proportions. PMID- 4039521 TI - Integrity, histologic organization and renewal ability of rat gastric and duodenal mucosa under conditions of a normoprotein dietary regime and chronic alcohol ingestion. Study I. PMID- 4039522 TI - Evaluation of the quantitative state of individual cell types in rat gastric and duodenal mucosa during normoprotein nutrition and chronic ethanol intake. Study II. PMID- 4039523 TI - [Therapeutic evolution of non-seminomatous cancers of the testicle]. PMID- 4039524 TI - [Male infertility with chromosomal abnormalities. I. XYY syndrome]. AB - Chromosomal abnormalities are found in a considerably high percentage of cases of male infertility, in particular azoospermia. We report a case of the XYY syndrome and review the literature. A 36-year-old man, a factory hand, presented with infertility. He was safely delivered at term as a fourth child when his father was 41 years old and his mother 38. He had no delinquent or criminal record. His height was 179 cm, weight 75 kg and distance of extended hands 184 cm. No gynecomastia was noticed. Both testes were 8ml in size and growth of pubic hair and penis were normal. Severe oligozoospermia was identified in semen analysis. Seminal vesiculography showed pathological dilatation of the seminal vas end. The testicular biopsy specimens revealed spermatogenic arrest for the most part. Chromosomal analysis showed 47, XYY karyotype; and, two Y-chromatin was revealed in cultured lymphocytes. Though plasma gonadotropin levels were high, testosterone, estradiol, prolactin, TSH, GH, T3 and T4 levels were within normal limits. Pituitary reserve function for secreting gonadotropins and Leydig cell reserve function to secrete testosterone have been found to be almost normal. PMID- 4039525 TI - [Fundamental studies on intravesical instillation of cis-diamminedichloroplatinum for treatment of urinary bladder tumors. I: On the effects of intravesical instillation of cis-diamminedichloroplatinum in normal beagle dogs]. AB - Cis-Diamminedichloroplatinum (II) (DDP) is one of the most effective agents in the treatments of advanced bladder cancer, but little is known of its local and systemic toxicity when it is instilled intravesically. The objectives of this experiment were to study the local and systemic toxicity of intravesical DDP in order to know whether intravesical DDP is applicable for prophylaxis and/or definitive treatment of superficial bladder cancers. Six female Beagle dogs were used for the 48-hour retention study and 2 mongrel dogs were used for the 3-hour study. Plasma and bladder platinum concentration were measured following intravesical DDP, and also histopathological examination, urinalysis, complete blood count and blood chemistry were performed in order to know the toxicity of intravesical DDP. Plasma platinum concentration was not elevated significantly and no remarkable changes were observed in blood examinations after intravesical DDP. Bladder tissue platinum concentration was significantly elevated up to 16.96 micrograms/g . wet after 3 hours DDP retention and 4.02 +/- 2.8 micrograms/g . wet after 48 hours retention in dogs. At present, intravesical instillation of DDP seems to have minimum local toxicity and no systemic toxicity, but further study is necessary for long term topical instillation of DDP. PMID- 4039526 TI - Cryptosporidiosis. PMID- 4039527 TI - Coronary artery disease in hypertrophic cardiomyopathy. PMID- 4039528 TI - Zinc bioavailability and infant formula. PMID- 4039529 TI - Changes in hepatic superoxide dismutase activity in alcoholic monkeys. AB - The hepatic concentrations of copper, zinc and manganese, the activity of the mitochondrial enzyme manganese-superoxide dismutase (MnSOD), and the activity of the cytosolic enzyme copper-zinc SOD (CuZnSOD) were measured in control and ethanol-fed monkeys. In the ethanol-fed group, liver Zn levels were decreased while the Mn concentration was increased. The activity of MnSOD was higher in the ethanol-fed group while the activity of CuZnSOD tended to be lower. The finding of increased activity of MnSOD is consistent with the finding of enlarged mitochondria and increased liver Mn in the ethanol-fed group. Increased MnSOD may reflect substrate induction, since superoxide anions are generated by ethanol metabolism. On the other hand, insufficient CuZnSOD activity may contribute to increased ethanol-induced lipid peroxidation with resultant mitochondrial damage. Thus, the chronic consumption of ethanol results in altered levels of trace minerals and SOD activities in the liver which in turn may contribute to hepatic injury. PMID- 4039530 TI - Cisplatin nephrotoxicity. Correlation with plasma platinum concentrations. AB - Plasma platinum concentrations were measured in 45 patients receiving 46 courses of cisplatin (DDP) 100-120 mg/m2 and in 21 patients receiving 35-60 mg/m2. Samples were drawn 5 minutes, 24, and 48 hours following completion of the DDP infusion. Nephrotoxicity was defined as a greater than 50% increase in serum creatinine measured at 24 and/or 48 hours when compared to the baseline pretreatment value. In patients receiving DDP 100-120 mg/m2, 5/20 with 5-minute plasma platinum concentrations greater than 6 micrograms/ml developed nephrotoxicity; 0/26 with concentrations less than 6 micrograms/ml became nephrotoxic (p less than 0.05). Concentrations at 24 and 48 hours in toxic and nontoxic patients were similar. Five-minute plasma platinum concentrations in excess of 6 micrograms/ml did not occur in the 21 patients receiving DDP 35-60 mg/m2. Only one of these 21 patients became nephrotoxic. The data suggest that an increased incidence of acute nephrotoxicity is related to high peak plasma platinum concentrations. PMID- 4039532 TI - The importance of primary diagnosis in perinatal death. AB - In a referral perinatal center a detailed study was made of all the perinatal deaths that occurred during 1 year; they were analyzed according to primary diagnoses on the basis of a classification by R. L. Naeye which included the placenta. This method points to the areas in which special efforts at prevention should be made, and it should become a reliable basis for comparison. PMID- 4039531 TI - A new X-linked syndrome with muscle atrophy, congenital contractures, and oculomotor apraxia. AB - Six men from three generations of one family had manifestations of a possible new syndrome. All had congenital contractures of the feet at birth, a slowly progressive predominantly distal muscle atrophy, dyspraxia of the eye, face, and tongue muscles, and mild mental retardation. The pedigree is compatible with X linked recessive inheritance with no detectable manifestations in the obligate carriers. Linkage analysis excludes close linkage with the Xg locus and a polymorphic DNA sequence from the long arm of the X chromosome (DXS17). PMID- 4039533 TI - Urethral isolation of the genital mycoplasmas and Chlamydia trachomatis in women with chronic urologic complaints. AB - Eighty-six abacteriuric women with chronic urologic complaints were studied to determine the relationship of Chlamydia trachomatis, Mycoplasma hominis, and Ureaplasma urealyticum to their symptoms or diagnoses. All patients had urethral scrape specimens for isolation of the three organisms as well as a detailed urologic history and urodynamic evaluation. Thirty-three of 86 patients (38%) had positive urethral ureaplasma cultures; seven had concurrent M. hominis isolation. No patient had M. hominis as the only urethral isolate and none had a positive C. trachomatis culture. There were no significant differences in urologic symptoms or in urodynamic diagnoses between Ureaplasma culture-positive and culture negative subjects. It was also found that colonization of the urethra with Ureaplasma decreased with increasing age and with hypoestrogenism. PMID- 4039534 TI - Medical factors in hyperactive and normal children: prenatal, developmental, and health history findings. AB - Guided by the goal of documenting the natural course of the life histories of a large sample of hyperactive children and their control counterparts, this research reports the extent to which prenatal, developmental, and health history factors distinguish hyperactive and control groups, as well as the relative contributions of the various medical factors. Results indicate that prenatal factors, rather than those occurring later in the child's medical history, are the best predictors of subsequent hyperactive diagnosis. PMID- 4039535 TI - Food restriction increases torpor and improves brown adipose tissue thermogenesis in ob/ob mice. AB - Restricting the food intake of the genetically obese (ob/ob) mouse is known to ameliorate its cold intolerance. Cold intolerance of the ob/ob mouse is associated with defective thermogenesis in its brown adipose tissue. The objective of the experiments was to find out whether food restriction could increase the thermogenic function of brown adipose tissue of the ob/ob mouse. Obese and lean mice were fed a restricted amount of chow in one meal per day for 3-7 mo. Both lean and ob/ob mice were torpid (rectal temperature of approximately 32 degrees C) in the early morning and aroused spontaneously to a normal body temperature before the anticipated meal time. Obese mice were also torpid during the dark phase, whereas lean mice were active and had a normal body temperature at this time. Brown adipose tissue was in a thermogenically inactive state (low level of mitochondrial GDP binding) in torpid lean and ob/ob mice but became thermogenically active (increase in mitochondrial GDP binding) during stimulated arousal when body temperature increased by 6-7 degrees C in 15-30 min. Ad libitum fed ob/ob mice had a normal diurnal rhythm in a rectal temperature that was at a lower level than in lean ad libitum-fed mice. They did not raise their rectal temperatures when stimulated and no activation of brown adipose tissue thermogenesis occurred under these conditions. Food restriction increased the capacity of both lean and ob/ob mice to raise their metabolic rate in response to injection of noradrenaline, indicating an increased capacity for thermogenesis in their brown adipose tissue.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4039536 TI - Hypothalamic obesity, brown adipose tissue, and sympathoadrenal activity in rats. AB - Obesity-producing, hypothalamic knife cuts and ventromedial hypothalamic (VMH) lesions in ad libitum-fed adult rats increased intake of a high-fat diet (123 and 130%) and energy retention (880 and 1,099%) during the 4-wk period postsurgery; even when pair fed to control rats, energy retention of the knife-cut and lesioned rats was still elevated (105 and 155%). Thermogenic capacity of brown adipose tissue (BAT), estimated from guanosine diphosphate (GDP) binding to BAT mitochondria, was unchanged in hyperphagic knife-cut and VMH-lesioned rats and was reduced approximately 50% when these rats were pair fed to controls. Urinary excretion of norepinephrine (NE) was approximately twofold higher in ad libitum fed, knife-cut, and lesioned rats than in control rats; restriction of energy intake decreased NE excretion to control values. Rates of NE turnover in heart paralleled urinary NE excretion, whereas NE turnover in BAT was generally not increased in the hyperphagic rats. Urinary epinephrine excretion, an index of adrenal medullary activity, was depressed in all knife-cut and VMH-lesioned rats. Hyperphagia coupled with a lack of increased heat production in BAT causes gross obesity in ad libitum-fed, knife-cut, and VMH-lesioned rats, whereas obesity in pair-fed rats develops in part at least as a result of reduced heat production by BAT. PMID- 4039537 TI - Somatomedin C/insulinlike growth factor I during liver regeneration in the rat. AB - We measured immunoreactive somatomedin C/insulinlike growth factor I (Sm C/IGF I) in blood and tissues of rats following partial hepatectomy (PH) to determine a possible regulatory role for this growth factor in liver regeneration. From a mean value of 0.66 U/ml +/- 0.19 before PH, the serum Sm C/IGF I rose to 1.09 +/- 0.08 1 h after PH [P less than 0.001 vs. sham-hepatectomized (SH) values]. Concurrently there was a twofold rise in serum aspartate aminotransferase, suggesting that the rise in Sm C/IGF I may be the result of hepatocellular injury rather than a specific secretory event. In the subsequent 22 h, serum Sm C/IGF I of PH rats fell to 0.31 +/- 0.06 U/ml, compared with 0.73 +/- 0.03 in SH rats. During this time, liver concentrations of the peptide declined to 30% of basal, whereas lung and kidney fell to only approximately 60% of basal. As the Sm C/IGF I declined, hepatic DNA synthesis increased 10-fold in PH animals. Our results, therefore, do not support a mitogenic role for Sm C/IGF I in the regulation of liver regulation. Food consumption was markedly depressed in the 22 h after PH (20.8 +/- 2.6 vs. 4.33 +/- 2.9 g/day; P less than 0.001). PH and pair-fed SH rats had serum Sm C/IGF I concentrations that were indistinguishable (0.31 +/- 0.06 vs. 0.35 +/- 0.11 U/ml), although liver tissue concentrations were lower in PH rats (0.04 +/- 0.01 U/g vs. 0.07 +/- 0.02).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4039538 TI - Compensatory mechanisms in response to an elevated hepatic oxygen consumption in chronically ethanol-fed rats. AB - During conditions that elevate hepatic oxygen consumption (VLO2), oxygen delivery, or oxygen extraction may also increase, acting as compensatory mechanisms. VLO2 was quantitated by an in vivo method in chronically ethanol-fed rats to establish whether VLO2 was increased and what compensatory mechanisms might ensue. VLO2 was increased 45% (0.32 +/- 0.02 ml O2 X min-1 X 100 g body wt 1; P less than 0.001) in rats chronically fed ethanol for 8 wk, while VLO2 (0.28 +/- 0.04; P = NS) was not increased in chronically ethanol-fed rats withdrawn from ethanol 20 h before study compared with control rats (0.22 +/- 0.01). Oxygen delivery was increased 31% (P less than 0.05) in ethanol-fed rats and adequately compensated for the increased VLO2. Hepatic artery blood flow did not increase in ethanol-fed rats, indicating a lack of hepatic artery vasodilation in response to the elevated VLO2. As a result, a greater percentage of oxygen delivery was supplied via portal venous blood flow that has a reduced oxygen content. These observations might suggest that ethanol-fed rats may have a decreased reserve for maintaining an adequate oxygen supply to the liver and may be at an increased liability for developing hepatic hypoxia if oxygen delivery and/or extraction were compromised. PMID- 4039539 TI - Measurement of glomerular filtration rate in conscious unrestrained rats with inulin infused by implanted osmotic pumps. AB - A method is described for determining glomerular filtration rate (GFR) in conscious unrestrained rats without extracellular volume expansion. The glomerular marker used was 14C-labeled inulin infused in the minimal fluid volume of 1 microliter/h by intraperitoneally implanted osmotic minipumps. The workability, reproducibility, and precision of the technique was evaluated in sham-operated (sham) and uninephrectomized (UNI-NX) rats for 6 days. In six sham operated rats the clearance of [14C]-inulin calculated from the plasma value obtained in a blood sample taken at 10 A.M. before food consumption was (means +/ SE): day 1 after pump implantation: 1.38 +/- 0.05; day 2: 1.27 +/- 0.05; day 3: 1.46 +/- 0.16; day 4: 1.45 +/- 0.15; day 5: 1.33 +/- 0.08; day 6: 1.38 +/- 0.11 ml/min. In six UNI-NX rats the corresponding values were: day 1: 0.88 +/- 0.04; day 2: 0.79 +/- 0.05; day 3: 0.91 +/- 0.03; day 4: 0.91 +/- 0.03; day 5: 0.83 +/- 0.06; day 6: 0.87 +/- 0.05 ml/min. When determined on day 2, 3, or 6 at 6 P.M., i.e., at the end of the food consumption period, [14C]inulin clearance was increased in all animals compared with the value determined at 10 A.M. in the fasted state. The use of implanted osmotic minipumps for delivering a glomerular marker such as [14C]inulin allows the determination of GFR in conscious unrestrained rats with normal fluid balance conditions. This method appears to be particularly appropriate for studying the influence of the intake and composition of food on GFR in physiological conditions. PMID- 4039540 TI - Volumetric aerobiological survey of conidial fungi in the North-East Netherlands. II. Comparison of aerobiological data and skin tests with mould extracts in an asthmatic population. AB - A study was undertaken to see whether the principal airborne fungi in the North East Netherlands were also found to be the most reactive in skin testing. Atmospheric samples were taken weekly with the Andersen sampler, from April 1981, up to and including, June 1983. At the same time skin tests of 833 patients referred to the outpatient Departments of Pulmonology and Allergology, because of recurrent bronchial obstructive complaints and a suspected allergy, were studied for strongly positive skin reactivity to fungi. 4.6% of the patients reacted with a wheal of 10 mm diameter or more to one or more of the tested fungi. Almost three-quarters of the airborne fungal "flora" was composed of seven genera, namely (in order of occurrence): Cladosporium (42.6%), Botrytis (8.6%), Yeasts (7%), Penicillium (5.8%), Basidiomycetes (5.7%), Aspergillus (3.7%), and Alternaria (0.9%). In skin-testing, however, a different order of occurrence existed: namely: Beauveria (6.8%), Botrytis (6.1%), Aspergillus (4.7%), Mucor (3.8%), Epicoccum (3%), Cladosporium (2.3%), and Alternaria (1.1%). It is concluded that the most prevailing airborne moulds are not necessarily the most potent allergens, at least in skin testing. Aspergillus and Botrytis showed a high sensitization rate, while Cladosporium and Alternaria did not. Botrytis deserves further study because of its frequent airborne occurrence and marked allergenic properties. PMID- 4039541 TI - A rapid and sensitive high-performance liquid chromatographic assay for 6 mercaptopurine metabolites in red blood cells. AB - A highly sensitive and rapid assay for the detection of 6-mercaptopurine metabolites in the red blood cells of leukemic patients receiving the drug has been developed. The method employs a batch-chromatographic procedure using a mercurial cellulose resin to selectively absorb thiol compounds combined with separation by high-performance liquid chromatography using a Partisil-SAX column and uv detection. This method permits detection of 6-thioinosine monophosphate, 6 thiouric acid, and 6-thioguanosine mono-, di-, and triphosphates in patient samples with a sensitivity of 5-10 pmol. No 6-thioinosine di- or triphosphates were detected in patient samples. The results of our study indicate that 6 thioguanosine triphosphate is the major metabolite of 6-mercaptopurine retained by red blood cells after oral or iv administration of the drug. PMID- 4039542 TI - Selective, rapid removal of the vitamin D-binding protein and its sterol ligands from human and bovine plasma. AB - Rapid and selective removal of plasma vitamin D-binding protein was effected by the serial passage of plasma over four columns of agarose containing covalently linked skeletal muscle G-actin. By maintaining an actin-to-binding protein molar ratio of at least 4 to 1 throughout, greater than 99% of the binding protein was removed from the fourth column's eluate. In contrast, 87% of the total plasma or serum protein applied was recovered, and electrophoretic analyses of human and bovine sera that had undergone these affinity chromatography steps revealed no major alterations in protein distribution. The procedure also removes vitamin D sterols selectively, with preference for 25-hydroxycalciferol (90% removal) over 1,25-dihydroxycalciferol (65-70% removal) and calciferol (70% removal), in accordance with the known affinity displayed by the binding protein for these sterol ligands. Recovery of other serum constituents (cortisol, proteins, peptide hormones, calcium and alkaline phosphatase) was excellent, further confirming the selectivity of the technique. Utilizing vitamin D-deficient serum, serum depleted of the vitamin D-binding protein was not distinguishable from control serum in supporting the growth of human fibroblasts in vitro. In comparison with other methods to remove serum-binding protein or sterols, the present technique is more selective and can be used for mammalian and avian sera. Material so prepared could prove useful for studies of the cellular access, metabolism, and effects of vitamin D sterols in vitro. PMID- 4039543 TI - Fluid-phase and adsorptive endocytosis in ciliated epithelial cells of the rat ductuli efferentes. AB - Ciliated cells of the ductuli efferentes show at their apex a discrete endocytic apparatus composed of small vesicles connected to or subjacent to the apical plasma membrane, small apical membranous tubules, and pale multivesicular bodies. Deeper in the cytoplasm, there are acid phosphatase-positive denser, multivesicular bodies and secondary lysosomes showing an electron-dense cortex and a crystalline, paler stained core. Cationic ferritin and concanavalin A ferritin used to demonstrate adsorptive endocytosis, when injected into the rete testis, rapidly reached the lumen of the ductuli efferentes. At 1 min after injection, these tracers were seen bound to the apical plasma membrane of ciliated cells and within small endocytic vesicles and by 5 min in narrow apical tubules. At 15 and 30 min after injection, the tracers appeared in pale multivesicular bodies while at 1 hr they were found within dense multivesicular bodies. At 2 hr and longer time intervals these tracers accumulated within secondary lysosomes. Native ferritin, concanavalin A-ferritin in the presence of alpha-methyl-D-mannoside, and horseradish peroxidase or albumin-colloidal gold complexes were used to analyze fluid-phase endocytosis. At various intervals following their injection into the rete testis, these tracers presented a distribution identical in all respects to that described for cationic ferritin and concanavalin A-ferritin. In the present work, none of the above tracers were transported to the abluminal aspect of the ciliated cells. These cells, like the nonciliated epithelial cells of the ductuli efferentes are thus involved in adsorptive as well as in fluid-phase endocytosis. PMID- 4039544 TI - Harlequin color change in an infant during anesthesia. PMID- 4039545 TI - Control of Isospora suis-induced coccidiosis on a swine farm. AB - Results of a program designed to control neonatal porcine coccidiosis on a total confinement, farrow-to-finish swine farm are reported. The control program consisted of washing, phenol disinfection, and steam cleaning of farrowing houses and treatment of sows with amprolium HCl before and after farrowing. Before initiation of the control program, 88.9% of the sows examined in the farrowing house were negative for coccidian oocysts, 9.9% were positive for Eimeria spp, and 1.2% were positive for Isospora suis. Most pigs nursing on sows before initiation of the control program had diarrhea at 5 to 10 days of age, which led to dehydration and weight loss. Morbidity was high, and mortality was moderate. Composite fecal samples from these litters were all positive (100%) for I suis. After initiation of the control program, 99.6% of the sows examined in the farrowing house were negative for coccidian oocysts and 0.4% were positive for Eimeria spp. Clinical signs of coccidiosis were rarely present in nursing pigs examined after the control program was initiated; however, I suis was still present in 19.8% of the composite fecal samples from pigs examined. An association between oocyst production in sows and I suis infections in pigs was not found in the present study. Oocysts of Eimeria spp were not found in the feces from the pigs. PMID- 4039546 TI - Oncogenic osteomalacia and renal adenomatoid dysplasia. PMID- 4039547 TI - Retinal manifestations of thrombotic thrombocytopenic purpura (TTP) following use of contraceptive treatment. AB - An 18-year old woman, suffering from thrombotic thrombocytopenic purpura (TTP) disease after taking an oral contraceptive, developed bilateral retinal elevations in the posterior pole with Elschnig spot formation without visual acuity impairment. Clinical and laboratory evaluation combined with intensive medical and surgical therapy (splenectomy) caused regression of the ocular and general findings. We believe that the ocular pathologic findings in this clinical case are due to injury in the choroidal vasculature and the pe layer as a manifestation of the TTP disease. PMID- 4039548 TI - Nasal blood flow and airway resistance. Canine study. AB - Nasal blood flow was measured in anesthetized dogs by an electromagnetic flow sensor placed around the terminal branch of the internal maxillary artery, the major arterial supply to the nasal mucosa. Nasal airway resistance was monitored simultaneously by recording the transnasal pressure when airflow through the nasal cavity was maintained constant. Phenylephrine decreased nasal blood flow and airway resistance while albuterol (salbutamol) did the opposite. Prostaglandin E1 increased nasal blood flow but decreased airway resistance. The present study demonstrates that nasal vascular and airway resistance may change in parallel or opposite directions, implying that nasal airway resistance cannot be used to assess the vascular situation in the nose. PMID- 4039549 TI - [Fructose utilization by hepatocytes isolated from fed obese fa/fa Zucker rats. Metabolic fate of fructose in the absence of the modulator]. AB - The utilization of fructose by isolated hepatocytes was investigated in fed obese Zucker fa/fa rats compared with their lean littermates (Fa/?) and Sprague-Dawley rats. Hepatocytes were incubated during 3 h using U14C fructose (20 mM). Our results show: a significant increase of fructose consumption, glucose, lactate and pyruvate production and faster turnover of glycogen by fa/fa rats. In these animals, synthesis of acylglycerol was also significantly enhanced. Our results suggest that fructose in fa/fa rats was used preferentially as precursor for lipid synthesis not only by the liver but also by the adipose tissue after a prior transformation into glucose by hepatocytes. All these abnormalities result in an accumulation of acylglycerols maintaining an obesity state in fa/fa rats. PMID- 4039550 TI - Optimum time sequence for the administration of cyclophosphamide and other drugs in vivo. AB - The significance of time interval for administration of a second drug after a first dose of cyclophosphamide (CTX) was studied for a human ovarian, lung, and colon carcinoma line growing as xenografts in nude mice. The effects of combination of two drugs were found to be dependent on the interval between the administration of each drug. The most effective chemotherapy schedules were those in which adriamycin (ADM) or CTX were sequenced to coincide with the time point where the tumour was regrowing from the single dose of CTX. The variation of the cell kinetic parameters, as estimated by flow cytometry analysis, could not be correlated with the antitumour action of the drug combination. PMID- 4039551 TI - Macrocyclic trichothecene toxins produced by Stachybotrys atra strains isolated in Middle Europe. AB - A total of 17 strains of Stachybotrys atra isolated in Hungary and Czechoslovakia were cultured on Sabouraud agar, and the toxins produced by them were chemically analyzed by gas-liquid chromatography, high-pressure liquid chromatography, and mass spectroscopy. Furthermore, brine shrimp (Artemia salina) bioassay was used for the determination of toxicity of the compounds examined. Macrocyclic trichothecenes (satratoxins H and G, roridin E, and verrucarin J as well as two other unidentified macrocyclic trichothecenes) were found in all of the cultures tested. The identities of satratoxins H and G, roridin E, and verrucarin J were qualitatively determined by high-pressure liquid chromatography and gas-liquid chromatography. The ratio of satratoxins H and G and roridin E was found to be similar in each of the strains tested, but the amount of verrucarin J found was different in each of them. One of the unidentified macrocyclic trichothecenes was equivalent to the compound isolated by Harrach et al. (Harrach et al., Appl. Environ. Microbiol. 41:1428-1433, 1981). The other one proved to be a newly isolated macrocyclic trichothecene toxin. Stachybotryotoxicosis, one of the oldest mycotoxicoses known, and a serious problem in Middle Europe (Gy. Danko, Magy. Allatorv. Lapja 31:226-232, 1976), is believed to be caused by macrocyclic trichothecene toxins produced by Stachybotrys atra (R. M. Eppley, in Rodricks et al., ed., Mycotoxins in Human and Animal Health, p. 285-293, 1977). Forty years ago, the death of animals in the Soviet Union was associated with this fungus (C. U. Ruhliada, in Proceedings of the All-Union Sci. and Tech. Conf., p. 47-51, 1980).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4039552 TI - [Preoperative adjuvant chemotherapy of skeletal and soft tissue sarcomas]. AB - Preoperative adjuvant chemotherapy for skeletal and soft tissue sarcomas requires: (1) correct identification of the effective postoperative adjuvant chemotherapy, (2) eradication of any of the micrometastatic foci that may have already occurred in many of the patients with these sarcomas, (3) easier and safer limb-salvage procedure, being clearly defined, with shrinkage of the primary lesion. For this purpose, a preoperative adjuvant chemotherapy regimen making practical use of intra-arterial CDDP (cis-dichlorodiammineplatinum II) infusion is desired in multi-drug combined chemotherapeutic treatment, including HDMTX (high-dose methotrexate), ADR (adriamycin) and CDDP. In this paper, the clinical application of preoperative adjuvant chemotherapy to skeletal and soft tissue sarcomas with combination of HDMTX and CDDP is presented in the light of the observations of tumor response to these anticancer agents, and the possibility of to establishing a new preoperative adjuvant protocol is discussed. PMID- 4039553 TI - [Effect of combined use of adrenocortical hormones and domperidone as anti emetics during cisplatin therapy]. AB - Eighteen patients received repeated administrations of cisplatin in relatively large amounts (55-75-100 mg/m2) given systemically by drop infusion. As antiemetic treatments, the following were scheduled: on the day before; prednisolone 30mg (3 X p.o.), immediately before; methylprednisolone 500mg (i.v.), and 3 hours after administration of cisplatin ; methylprednisolone 500mg (i.v.) and domperidone 60 mg (suppo.). Domperidone was given twice a day for one week. Nausea, vomiting and anorexia were studied objectively for two weeks. At a dose of 75 mg/m2 of cisplatin, the occurrence and the duration of nausea and vomiting were effectively reduced by the regimen; nausea was observed in 67% of all cases (average duration: 3.3 days) and vomiting was experienced in 40% (1.2 days). Anorexia was observed in 67% of cases and lasted longer (5.2 days). The severity and duration of these side effects of nausea, vomiting and anorexia seemed to appear in a manner related to the dose of cisplatin given, but even at a dose of 100 mg/m2, the regimen described above reduced the patients' discomfort to acceptable levels. No remarkable side effect of this anti-emetic regimen was evident. PMID- 4039554 TI - [Evaluation of the effectiveness of cisplatin in the treatment of disseminated cancer of the prostate]. PMID- 4039555 TI - Cimetidine blocks testosterone synthesis. AB - Although an assortment of endocrine dysfunctions are reported in men treated with cimetidine hydrochloride, gonadotropin and sex steroid levels are usually normal. A 66-year-old man with previously normal sexual function presented with breast tenderness and sexual dysfunction after receiving cimetidine. His plasma testosterone level was low, and elevated gonadotropin levels suggested a primary testicular disorder. His sexual dysfunction improved and his plasma testosterone level rose to normal after cimetidine therapy was discontinued. Readministration of cimetidine therapy resulted in the prompt recurrence of his sexual problems and low testosterone level. A reversible defect in 17-beta-hydroxysteroid dehydrogenase is the mechanism postulated to have caused his low testosterone level. While the frequency of this abnormality is uncertain, its reversible nature and the wide use of cimetidine make it an important cause of sexual dysfunction in men. PMID- 4039556 TI - Splenectomy and extravascular platelet destruction in thrombotic thrombocytopenic purpura. AB - Intravascular platelet deposition has been considered an essential pathophysiologic mechanism in thrombotic thrombocytopenic purpura. Splenectomy resulted in prompt and sustained hematologic improvement in a patient with the chronic form of the disease. The response to splenectomy, normal plasma levels of secretable platelet proteins, and phagocytosis of erythrocyte fragments and platelets by splenic macrophages demonstrated by electron microscopy suggest that platelet destruction may occasionally be predominantly extravascular in this disease. PMID- 4039557 TI - Nocturnal penile tumescence and penile responses in the waking state in diabetic and nondiabetic sexual dysfunctionals. AB - This study compared diabetics with sexual dysfunction, nondiabetics with sexual dysfunction, and a group of controls on nocturnal penile tumescence (NPT) during three nights in a sleep laboratory, and penile response to erotic stimulation in the waking state on one of the nights. Both diabetic and nondiabetic dysfunctionals showed less erectile response to erotic films and tape than controls but did not differ from each other. In contrast, the diabetic dysfunctionals showed significantly weaker NPT response than both the nondiabetic dysfunctionals and the controls, and 58% of them (contrasted with 23% of nondiabetic dysfunctionals and 0% of controls) would be classified as organic using minimal NPT (less than 11.5 mm maximal increase in penile circumference during any nocturnal erection) as the sole criterion. There was a significant relationship between NPT and waking erections in response to erotic stimuli, especially in the diabetic dysfunctionals and the controls. PMID- 4039558 TI - Personality variables and circumstances of sexual assault predictive of a woman's resistance. AB - The present study investigated degree of resistance to sexual assault as a function of personality variables and circumstances of assault. Death anxiety was the personality variable most predictive of high resistance. The profile of the high-resistant women showed that the absence of a weapon, lower death anxiety, and knowing the assailant accounted for 66% of the variance. It was inferred that the life-threatening aspects of the rape situation are of great importance in determining a potential victim's reaction. PMID- 4039559 TI - [Spatial reorganization of the organelles of catecholamine-synthesizing group A1 neurons during emotional stress]. AB - Dynamics of spatial reorganization of organellas in catecholamine-synthesizing neurons of A1 group, that participate in reactions of the cardiovascular control, have been studied under normal conditions and under stimulation of the ventromedial nucleus in the hypothalamus. During transition of the hypertensive reaction into the hypotensive one, concentration of various organellas in the Golgi complex area and in the perinuclear zone is intensively increasing. Deep mutual nucleocytoplasmic invaginations appear. The spatial reorganization of the organellas in the neuron demonstrates that some new integrations take place in its metabolic system and reflects its another qualitative state. This serves as an impulse for structural adaptive modifications of the synaptic apparatus. There is a reason to suppose that one of the ways for organization of the alive system stability to an emotional stress is the way of reorganization of the connections, creation of another physiological architecture of the functional system, that can ensure the adaptive reactions of the organism to emotional overstrains. PMID- 4039560 TI - Cellular mechanisms of resolution of drusen after laser coagulation. An experimental study. AB - Naturally occurring drusen in two eyes of a rhesus monkey resolved after the application to the retina of mild laser coagulation. Clinically, resolution took place approximately nine days following treatment. The cellular mechanism for resolution was observed by light and electron microscopy over a time period of three days to six weeks after treatment. A previously unidentified phagocytic cell, probably derived from the pericyte of the choriocapillaris, was observed to remove drusenoid material after laser photocoagulation. The cell appeared to be analogous to the mesangial cell of the renal glomerulus. PMID- 4039561 TI - The effect of alcohol intoxication on inflammation of the cornea. AB - New Zealand albino rabbits received daily intraperitoneal injections of alcohol (ethyl alcohol), 1.6 g/kg and the effect of short-term (three days) and long-term (six weeks) administration on corneal inflammation was studied. Both regimens produced an average peak serum concentration of more than 0.200 g/dL, a level consistent with gross intoxication in the majority of humans. Clinical signs of intoxication were present in all animals, manifested by a gross disturbance of equilibrium and gait. Neither regimen produced measurable liver damage. Nonetheless, following both regimens of alcohol administration, significantly fewer polymorphonuclear leukocytes invaded the corneas of animals receiving alcohol than invaded the corneas of simultaneously run controls receiving intraperitoneal saline. These data provide a mechanism to explain why an alcoholic individual might not cope with a corneal infection as well as a nonalcoholic person, an observation long thought to be true clinically. PMID- 4039562 TI - Aggressive behavior inhibition by serotonin and quipazine injected into the amygdala in the rat. AB - The effects on aggressive behavior, open-field activity, and pain threshold of bilateral microinjections of serotonin (20 micrograms) and quipazine (20 micrograms), the direct serotonergic receptor agonist, into the cortico-medial amygdala were investigated in Wistar rats. Both drugs significantly prolonged the attack latency in isolated killer rats (predatory aggression model), and suppressed the incidence of aggressive postures/attacks in shock-induced fighting test (affective aggression). The only difference in the open-field behavior was the lower number of central square entries in drug-treated compared to saline injected rats. None of the substances produced any significant change in jump threshold. It is concluded that stimulation of serotonin receptors within the amygdala produces inhibition of affective and muricidal behavior in isolated rats. The effect does not seem to be dependent on changes in general activity and pain sensitivity. PMID- 4039563 TI - Activation and stabilization of the catalytic unit of adenylate cyclase. AB - The requirements for stability and activity of the catalytic unit (C) of adenylate cyclase were investigated. After solubilization of bovine brain membranes in the zwitterionic detergent 3-[(3 cholamidopropyl)dimethylammonio]propane-1-sulphonate (Chaps), the catalytic unit was separated from the stimulatory guanine-nucleotide-binding protein (Gs) by gel filtration on Ultrogel AcA-34. The partially purified C unit was rapidly inactivated at 30 degrees C; 0.25 mM-ATP stabilized activity. Although C-unit activity was dependent on Mg2+ or Mn2+, stabilization by ATP did not require bivalent cations. Activity of the Ultrogel-AcA-34-purified C unit was increased by Ca2+ plus calmodulin and by phosphatidylcholine plus lysophosphatidylcholine; activity in the presence of both activators was significantly greater than with each alone. Calmodulin plus Ca2+ and phospholipids also stabilized C unit. The column-purified C unit was activated by forskolin; the effect of forskolin was additive to those of calmodulin plus Ca2+ and phospholipids. p[NH]ppG-stimulated adenylate cyclase activity was reconstituted by mixing samples from the gel filtration column containing Gs with C unit. Activation by Ca2+ plus calmodulin and Gs plus p[NH]ppG was additive; Ca2+ plus calmodulin did not alter the concentration of p[NH]ppG required for half-maximal activation. Results were similar with forskolin and Gs plus p[NH]ppG; the presence of one activator did not alter the effect of the other. These studies define conditions for separation of C unit and Gs from brain adenylate cyclase and demonstrate that ATP (in the absence of bivalent cations), phospholipids, calmodulin plus Ca2+, and forskolin all interact with C unit in a manner that is independent of functional Gs. PMID- 4039564 TI - Partial purification and characterization of the tissue plasminogen activator in nasal mucosa and nasal polyp. AB - Tissue plasminogen activator was partially purified from the inferior turbinate and nasal polyp, and its biochemical properties were investigated. Similar TPA peak positions were seen in the gel filtration chromatography of both tissues, and the molecular weight was approximately 65,000, which was comparable to TPA of pig heart (55,000-60,000). Activity of TPA from inferior turbinate was higher than that from nasal polyp. TPA from both tissues was completely inhibited by trans-aminomethyl cyclohexane carboxylic acid, dithiothreitol, and diisopropylfluorophosphate and had similar inhibition profiles to TPA from pig heart. All these findings indicate that TPA from both tissues is undoubtedly a plasminogen-activating enzyme and serine-type protease and would be biochemically identical. PMID- 4039565 TI - A progestin effect on lactate dehydrogenase in the human breast cancer cell line T-47D. AB - The human breast cancer cell line T-47D has high levels of progesterone receptor even in the absence of exogenously added estrogen. Because of this it is a good line in which to study aspects of progestin action. It has been shown by others that lactate dehydrogenase in MCF-7 cells is responsive to estrogen but not to progesterone. Other proteins in other systems have been found to be responsive to both estrogen and progesterone, often requiring priming by estrogen, presumably to produce sufficiently high quantities of progesterone receptor. Reasoning that lactate dehydrogenase in T-47D cells might be stimulated by progestins alone at physiological levels since these cells already have high levels of progesterone receptor, we now report that this is indeed the case. PMID- 4039566 TI - Involvement of cytochrome b5 in the hepatic microsomal metabolism of benzo(a)pyrene. AB - Ethanol consumption decreased the specific content of microsomal cytochrome b5 in both chow-and liquid diet-fed hamsters while cytochrome P450 levels were unchanged in chow-fed animals and increased in liquid diet-fed animals. Microsomes from animals receiving ethanol in their drinking water exhibited decreased rates of microsomal aryl hydrocarbon hydroxylase activity and postmitochondrial supernatant mediated mutagenicity of benzo(a)pyrene. In contrast, microsomes from hamsters receiving ethanol in liquid diets showed no changes in either of these two activities. When the observed rates of 7,8 and 9,10 diol formation per nmole P450 for chow-fed animals are plotted vs. the b5/P450 ratio a positive correlation was observed suggesting that cytochrome b5 participates directly in the microsomal metabolism of benzo(a)pyrene. PMID- 4039567 TI - The renal fractional clearance of platinum antitumour compounds in relation to nephrotoxicity. AB - The fractional renal clearance of platinum relative to inulin was measured in the conscious rat during the period 60-70 min after injection of the nephrotoxic drug, cisplatin, or its non-nephrotoxic analogues (trans-dichlorodiammine platinum II, carboplatin or iproplatin). The fractional clearance of platinum was between 3 and 4 for cisplatin and its analogues. Platinum from cisplatin and its trans isomer is essentially irreversibly bound whilst that from carboplatin and iproplatin is largely reversibly bound to blood proteins. Probenecid and triethanolamine both caused an increase whereas furosemide caused a decrease in the fractional clearance of total platinum from cisplatin. Choline chloride had no nett effect on the fractional clearance of total platinum. Both furosemide and triethanolamine made no significant difference to the severity of cisplatin induced nephrotoxicity. However, probenecid enhanced cisplatin induced nephrotoxicity and choline chloride was capable of blocking cisplatin induced nephrotoxicity. We conclude that the renal tubular transport of platinum is not per se responsible for the nephrotoxicity of platinum compounds. However, in the case of cisplatin, or one of its metabolites, renal tubular transport may be a prerequisite for nephrotoxicity. PMID- 4039568 TI - Progestogens with antimineralocorticoid activity. AB - The ability of 11 steroids with varying degrees of progestogenic potency to inhibit the renal actions of aldosterone was tested in adrenalectomized, glucocorticoid-treated rats. The rats were continuously infused with an isotonic solution of low sodium content (0.05% NaCl + 5.2% glucose, 3 ml/rat/h) supplemented with d-aldosterone [1 microgram/(kg X h)] resulting in a long lasting reduction in renal sodium excretion, increase in renal potassium excretion and hence decrease in the urinary Na/K-ratio. The test drugs were administered either subcutaneously or orally 1 h before start of infusion. Their antimineralocorticoid activity was judged by the increase in the aldosterone lowered Na/K-ratio in urine which was collected at hourly intervals for 15 or 21 h, respectively. Adrenalectomized, glucocorticoid-treated rats receiving an i.v. infusion without aldosterone were used for assessing possible mineralocorticoid effects of the steroids tested. D-Norgestrel, norethisterone acetate, 3-keto desogestrel (the active metabolite of desogestrel) and cyproterone acetate, respectively, did neither show antimineralocorticoid nor mineralocorticoid activity when injected subcutaneously at a dose of 53.3 mg/kg. In contrast, gestodene (26.7 or 53.3 mg/kg s.c., respectively), progesterone (53.3 mg/kg s.c.), spironolactone (26.7 mg/kg s.c.), spirorenone (13.3 mg/kg s.c.), 1,2 dihydro-spirorenone (13.3 mg/kg s.c.), or 1,2 alpha-methylene-spirorenone (13.3 mg/kg s.c.) exhibited significant anti-mineralocorticoid activity. Canrenone (53.3 mg/kg s.c.) slightly increased the urinary Na/K-ratio. This effect, however, was not significant. Gestodene, like spironolactone or progesterone, was devoid of aldosterone-like mineralocorticoid activity. With the exception of progesterone, the antimineralocorticoid activity of the steroids tested could also be demonstrated after oral administration. Based on the Na/K-ratio or the log (Na X 100)/K-ratio, the potency of each test compound relative to spironolactone was evaluated using regression analysis. The following results (average relative potency, spironolactone = 1.0) were obtained: gestodene: approximately 0.2; canrenone: approximately 0.3-0.35; spirorenone: approximately 7-8; 1,2-dihydro-spirorenone: approximately 8; 1,2 alpha-methylene-spirorenone: approximately 3.5. Progesterone which was evaluated after s.c. injection exhibited an average relative potency of approximately 0.35. Due to these results, gestodene may be regarded as the first progestogen of the nortestosterone series exhibiting a more natural, progesterone-like profile of activity.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 4039569 TI - Effects of the new eburnamenine derivative RU 24722 on EEG recovery and cerebral energy metabolism after complete ischemia. AB - The influence of a new eburnamenine derivative RU 24722 [(3 beta, 14 alpha, 16 alpha)-(+/-)-14,15-dihydro-20,21-dinoreburnamenin -14-ol] on post-ischemic EEG recovery was studied in N2O anesthetized rats subjected to 1 min of global compression cerebral ischemia. RU 24722 was compared with vincamine, dihydroergotoxine mesylate and nicergoline. Treatment with RU 24722 (2 mg/kg i.v.) significantly decreased the EEG recovery time and increased the electrocortical activity during the first phase of the post-ischemic recovery. Vincamine (2 mg/kg i.v.), dihydroergotoxine mesylate (0.5 mg/kg i.v.) and nicergoline (0.5 mg/kg i.v.) were devoid of activity. In an attempt to elucidate its mechanism of action, the influence of RU 24722 on changes in the cerebral metabolic energy reserves was studied in mouse brain after different periods of decapitation ischemia. The changes occurring during the first 10 s of ischemia were used to calculate the baseline cerebral metabolic rate (CMR). The activity of RU 24722 was compared with that of vincamine and pentobarbital. RU 24722 (10 mg/kg i.p.) significantly retarded glucose, phosphocreatine and adenosine triphosphate utilisation and lactate production. Vincamine (10 mg/kg i.p.) had no effect on cerebral energy substrates. Pentobarbital (100 mg/kg i.p.) markedly increased the tissue concentration of glucose and phosphocreatine and decreased lactate levels before and after ischemia. The improvement of EEG recovery suggests that RU 24722 may be therapeutically effective in cerebral insufficiency, and the decreased brain energy demand may be one of the mechanisms by which RU 24722 has a protective effect against cerebral ischemic damage. PMID- 4039570 TI - Pharmacokinetics of 3H-pipethiaden after single oral and intravenous administration in rats. AB - Tritium labelled anti-migraine drug 4-(1-methyl-4-piperidyliden)-4,9 dihydrothieno[2,3-c]-2-b enzothiepine (pipethiaden) was prepared. After oral and intravenous administration to rats not only the courses of total radioactivity in plasma and various organs were determined, but by means of TLC-radiometry also the levels of pipethiaden itself. After the oral dose 1.35 mg/kg the plasma levels of pipethiaden did not exceed 3.5 ng/ml. Some pharmacokinetic parameters (e.g. t1/2 el-4 h) were calculated by compartmental analysis of plasma levels. PMID- 4039571 TI - Bioavailability studies of etofibrate in rhesus monkeys. AB - Etofibrate (Lipo-Merz) is a newer antilipaemic agent that contains the nicotinic and clofibric acid moieties joined together through a diester link with ethylene glycol. The bioavailability of these moieties in etofibrate was compared to that from equimolar amounts of these drugs administered alone to rhesus monkeys (clofibric acid 354 mg, nicotinic acid 203 mg). For this comparative purpose, analytical methods were chosen which converted etofibrate and its initial metabolites into clofibric and nicotinic acid. Following this treatment, the rate and extent of bioavailability of unchanged nicotinic acid from etofibrate was significantly lower (P less than 0.01) than that from nicotinic acid alone. Mean peak whole blood levels of 11.9 micrograms/ml at 2.8 h and 35.3 micrograms/ml at 1.3 h, respectively, occurred after administration of etofibrate and nicotinic acid alone. The extent of bioavailability of clofibric acid hydrolysed from etofibrate was not significantly different (P greater than 0.05) from that from clofibric acid alone. However, mean peak plasma levels of 127.3 micrograms/ml at 3.6 h and 170.8 micrograms/ml at 2.4 h, respectively, occurred after administration of etofibrate and clofibric acid alone and were significantly different (P less than 0.01). The rates and extent of bioavailability of nicotinic acid or clofibric acid administered as a mixture were similar to that from these drugs administered alone. Thus either drug did not affect the absorption of the other in rhesus monkeys. The half-lives of nicotinic acid (in whole blood) and clofibric acid (in plasma) in rhesus monkeys when these drugs were administered alone were 9.9 h and 1.8 h, respectively. PMID- 4039572 TI - [Edema-protective effect of clobenoside]. AB - Intravenous administration of etacrynic acid induces protein rich oedema in hind legs of chloralose anaesthesized cats. Clobenoside was able to prevent the development of this oedema if administered prior to oedema provocation either orally or intravenously. The degree of inhibition of oedema development was quite similar after oral and intravenous administration, respectively, thus the bioavailability of clobenoside should be good. The half-life of orally administered clobenoside is prolonged as even 24 h after a single oral administration the activity was considerably high. Clobenoside did not influence blood pressure nor heart rate and did not produce any direct vasoactive effects. PMID- 4039573 TI - [Effects of continuous body stress and methandienone on the degradation of myofibrillar proteins in the guinea pig heart and soleus muscle]. AB - The influence of permanent physical stress (running training) and of the application of an anabole-androgenic steroid, 17-beta-hydroxy-17-methylandrosta 1,4-dien-3-on (metandienone, Dianabol) on the degradation rate of myofibrillar proteins of heart and soleus of male guinea-pigs was investigated. The rate of protein degradation was measured by the time-dependent loss of radioactive proteins after labelling with 14C-leucine in vivo. The investigations led to the following results: We found no significant change of the body or muscle weights of any of the guinea-pig groups examined. Only the combination of physical stress with metandienone showed a significant increase of the myofibrillar protein concentration as well as an increase of the specific activity of the myofibrillar proteins of heart and soleus. These findings could be the result of a decreased degradation rate of the myofibrillar proteins. The myofibrillar proteins of the heart were higher labelled than the myofibrillar proteins of the soleus. The concentration of myofibrillar proteins was higher in the soleus than in the heart. The 14C-leucine activity of the free amino acid pool was significantly higher in the heart than in the soleus in the first minutes after labelling. PMID- 4039574 TI - Acute effects of nifedipine on patients with chronic obstructive lung disease. AB - The bronchodilatory effect of nifedipine (Adalat) and the change of arterial blood gas in 5 normal and 25 patients with chronic obstructive lung disease (COLD) were investigated. 10 or 20 mg of nifedipine was orally administered. Before and 2 h after the administration, blood pressure (BP), heart rate (HR), arterial blood gas, respiratory resistance (Rrs) were measured and spirometry was assessed. Decrease of BP and increase of HR were observed in both normal and patient group. The patient group showed an increase of forced vital capacity (FVC) by 150 ml and forced expiratory volume (FEV 1.0) by 140 ml in average. In spite of the improvement of spirometry and Rrs, delta AaPO2 (alveolar arterial oxygen pressure difference) was increased in the patient group. It was considered, that the effect on the cardiovascular system was more remarkable than the bronchodilation, and the use of the drug alone as a bronchodilator may not be appropriate. It may be particularly effective in the cases with cardiovascular disease complicated with COLD. PMID- 4039575 TI - The effect of age on clinical pharmacokinetics of piracetam. AB - In this study the pharmacokinetics of 2-oxopyrrolidine-1-acetamide (piracetam, Nootrop), were studied in 10 geriatric patients with multiple diseases aged between 69 and 87 years. After intravenous administration of 6 g piracetam, the concentration of the drug in plasma was measured after 5, 10, 15 and 30 min as well as after 1, 2, 4, 6, 8, 10, 12 and 24 h. An analysis of laboratory diagnostic findings was carried out in parallel. The kinetic parameters were correlated with the laboratory diagnostic data and discussed together with the currently available results in the literature. The finding which seems to be of particular significance is that multimorbidity is a more important factor influencing the pharmacokinetics than age. PMID- 4039576 TI - Determination of compliance with riboflavin in an antidepressive therapy. AB - In a comprehensive study on the fate of amitriptyline (At, Laroxyl) in depressive patients, it was investigated whether their compliance could be controlled in analysing the concentration of riboflavin (vitamin B2) in urine. Therefore, they were medicated for 3 weeks with special tablets (Ro 4-1575/063) containing 150 mg At and 15 mg riboflavin. Different modalities or urine samplings were designed in order to establish the optimal conditions for testing compliance. Riboflavin, creatinine, At and nortriptyline were measured in urine, the tricyclic drugs also in plasma. The results show that compliance could be tested in analysing urine before and 4 h after the intake of the drug. However, this design was associated with a considerable subjective constraint for the patient. PMID- 4039577 TI - [The anti-inflammatory effect of a combination of dimethindene maleate and betamethasone in topical formulations]. AB - The antiinflammatory activity of three preparations (cream, ointment, jelly) of Fenistil Plus (betamethasone + dimethindene maleate) was shown by means of reflection densitometry, a new pharmacodynamic model. The three preparations led to restitution of the Tesafilm-stripped skin within 4 h. There was no significant difference in the efficacy of the preparations. After application of 10 g of the ointment the plasma levels of betamethasone remained within the limits of identification of the analytical method. An influence of the drug on the endogenous plasma hydrocortisone (cortisol) levels could not be found. PMID- 4039578 TI - [Fluorodensitometric determination of cytostatic acting Michael-adducts of alpha, beta-unsaturated aldehydes in biologic material]. AB - Alpha, beta-unsaturated aldehydes produce a selective cytostatic effect on tumor cells. By the formation of Michael adducts with cysteine, toxicity can be greatly reduced without impairing cytostatic effectiveness. To further enhance the selectivity of the toxic effect, it is necessary to be able to follow the agent's kinetics in the animal body. Among the analytic methods developed to this end, this paper represents the fluorescence derivatisation as a sensitive method for the determination of the Michael adducts of alpha, beta-unsaturated aldehydes in pharmaceutical preparations and in biological material. It is based on the reaction of the carbonyl groups with dansyl hydrazine. Determination is carried out by a combination of thin-layer chromatography with subsequent fluorodensitometric evaluation. The detection limit in blood is about 20 micrograms/ml. The relative standard deviation of this procedure ranges between 3 and 7%. PMID- 4039580 TI - [What can modern genetic methods contribute to clarifying the pathogenicity mechanisms of microorganisms?]. PMID- 4039579 TI - [The red thread: oncogenes and their convergence in cancer research]. PMID- 4039581 TI - [Problems of multiple tests and evaluations in drug research]. AB - The well known inferential statistical procedures only take into account the test of a single hypothesis or the estimation of a single parameter. In practical drug research the scientist in most cases is interested in multiple tests of several hypotheses or a simultaneous estimation of several parameters. After introducing the principal problems of simultaneous statistical inference several statistical methods are discussed. These methods can be applied to a variety of problems in drug research. PMID- 4039582 TI - [The role of significant tests in drug research. A comment on the work of Forst, "Problems of multiple tests and evaluations in drug research"]. PMID- 4039583 TI - Synthesis, metabolism, and disposition of the antiinflammatory 3-[2-(4 methylphenyl)-thioethyl]-sydnone-5-14C in the rat. AB - The synthesis, as well as the in vivo and in vitro disposition, of 3-[2-(4 methylphenyl)thioethyl]-sydnone-5-14C (5) in the rat is described. After intraperitoneal injection of a single dose of 5 in female Sprague-Dawley rats, the distribution and excretion of radioactive substances was monitored (24 h). Radioactivity in the blood declined in a biphasic manner with half-lives of 0.55 and 15.2 h for the alpha- and beta-phase, respectively. About 8% of the administered radioactivity was detected in feces and approximately 90% in urine (24 h). In 3.75 h, 50% of the radio-dose was excreted in the urine. Tissue distribution studies demonstrated a selective uptake of radioactivity only by the adrenal glands and the ovaries. The radioactivity in these organs reached a maximum approximately 1 h after dosing and then declined rapidly. None of the parent drug was excreted from such a single dose (i.p. injection) which indicated rapid in vivo metabolism. Nor could there be found any metabolites related to the whole structure, for example, the sulfoxide or aromatic hydroxy compounds. The sydnone 5, its sulfoxide and unconjugated metabolites were detected and quantitated by GC/MS methodology using unlabelled authentic samples. Radioactive carbon dioxide was not detected during the in vivo or in vitro experiments, nor was it released from alkaline urine samples upon acidification. Radiolabelled urinary metabolites were glycolic acid-1-14C 9 (34%), its glycine conjugate 10 (52%) and 3-vinylsydnone-5-14C 11 (4%).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4039584 TI - Comparison of the effects of nifedipine on ureter and coronary artery isolated from the dog. AB - The effect of nifedipine (Adalat) on isolated dog ureter was compared with that on isolated coronary artery. Nifedipine at a concentration of 10(-8) mol/l significantly decreased the frequency of ureteral rhythmic contractions evoked by potassium, and suppressed the force of these contractions at a concentration of 3 X 10(-8) mol/l. In potassium-contracted coronary artery strips, nifedipine at concentrations more than 3 X 10(-9) mol/l produced significant relaxations in a concentration-dependent manner. The results indicate that nifedipine is able to act inhibitorily on ureteral contractions, and inhibition of pace making activities in ureteral smooth muscle was suggested as a mode of action of nifedipine. PMID- 4039585 TI - [Autoradiographic studies of the distribution of 14C-endralazine in the mouse]. AB - In a macroautoradiographic study in pregnant and nonpregnant mice the distribution pattern of 14C-Endralazine (6-Benzoyl-3-hydrazino-5,6,7,8 tetrahydropyrido(4,3-c)-pyridazine- mesilate), a new direct vasodilator drug, was investigated, since earlier studies with minoxidil and hydralazine had shown apparent discrepancies between the relatively short elimination-half-life and the long pharmacological effect of the drugs. After a single oral administration of 5 mg/kg 14C-endralazine the initial high amounts of radioactivity in the gastro intestinal tract, the kidneys and the liver continuously decreased in the course of the 2nd to the 8th hour after application. 24 h after administration the drug was nearly completely eliminated from these organs except the liver. A remarkably high and persistent affinity of 14C-radioactivity to the blood vessel walls was found even 48 h after application which could explain the long acting pharmacological response to the drug. Only low levels of radioactivity were registrated in the fetus of pregnant mice. PMID- 4039586 TI - On the mechanism of bronchodilatation by etafedrine. AB - Effects of (-)-N-ethylephedrine (etafedrine) were studied on the tracheal chain preparation and the atria of the guinea pig and on the rabbit perfused heart. Contraction of the tracheal chain by acetylcholine or histamine was antagonized by epinephrine (adrenaline), etafedrine and ephedrine, the relative potencies being 91:1:0.3, respectively. Propranolol (5 X 10(-7) mol/l) completely antagonized the bronchodilator effect of 10(-4) mol/l etafedrine on the acetylcholine-evoked contraction. Etafedrine up to 3 X 10(-4) mol/l did not increase heart rate or force of contraction in guinea pig atria. In contrast to tyramine and ephedrine (both 10(-5) mol/l), etafedrine (10(-4) mol/l) failed to release 3H-norepinephrine (noradrenaline) in the perfused rabbit heart. Moreover, the concentration-dependent positive chronotropic and inotropic effects of norepinephrine in isolated atria were slightly, but not significantly enhanced by etafedrine. It is concluded that N-ethylation of ephedrine suppresses the indirect sympathomimetic activity and markedly enhances the efficacy on beta 2 adrenoceptors. Etafedrine appears to be a sympathomimetic agent with a selective activity on beta 2-adrenoceptors. PMID- 4039587 TI - The in vivo fate of topically applied dithranol in the skin of the hairless rat. A comparison of continuous and short contact application. AB - The fate in vivo of topically applied 1,8-dihydroxy-9-anthrone (dithranol, anthralin) was investigated in the skin of the hairless rat, using a specially designed drug delivery system (film). The film was applied on intact skin as well as on skin with an impaired barrier function (stripped skin). The distribution of the drug was examined either after continuous application or at selected times after short contact periods. The exposed skin was extracted with diisopropylether and free dithranol, its dimer and quinone assayed by quantitative HPLC analysis. The incorporation of trace amounts of 3H-dithranol and 14C-dithranol in the vehicle made it possible to quantify the fraction of penetrated drug which was insoluble in ether. With continuous application to intact skin (up to 24 h), extractable dithranol rapidly reached a plateau level (15 min) and was concentrated in the stratum corneum. Substantial dimer formation occurred in both normal and stripped skin. Ether insoluble material rapidly predominated over soluble material, especially when the stratum corneum was absent. However, on short contact application (0.5-1 h), ether soluble material (dithranol in the stratum corneum) was quantitatively predominant in the intact skin. Removal of the vehicle after a short contact time resulted in the disappearance of dithranol from the skin (normal and stripped). In intact skin, the drug was converted into ether insoluble material. In the stripped skin, this insoluble fraction remained constant over the duration of the experiment (24 h). PMID- 4039589 TI - Metabolism of benzydamine. AB - After an oral dose of 50 mg benzydamine to three volunteers, urinary metabolites were identified by mass spectrometric techniques. 50-65% of the dose was excreted unchanged with the urine. The main metabolic pathways were elimination of the dimethylaminopropyl group, elimination of the benzyl group, desmethylation, N oxidation, and hydroxylation of the benzene ring. Didesmethylbenzydamine and hydroxybenzydamine were excreted in form of their corresponding glucuronides. PMID- 4039588 TI - [Comparative studies on the tolerance of bioequivalent doses of intravenous methylxanthine preparations in healthy subjects]. AB - In a comparative tolerance study with two different intravenous methylxanthine preparations, a theophylline-ethylendiamine preparation (TE-reference preparation) was tested against a combination of theophylline, proxyphylline (7 (2-hydroxypropyl)-theophylline) and diprophylline (7-(2,3-dihydroxypropyl) theophylline) (Neobiphyllin; TPD = test preparation) in 10 healthy volunteers by a single blind cross-over design. Both preparations were infused under continuous control of vital parameters (blood pressure, pulse, respiration frequency, heart rhythm) as infusions (1 ampoule with 800 mg TPD or 1 short-infusion with 480 mg of TE for 20 min, each) up to the individual tolerance limit or the pre-defined limit of 3 ampoules/short infusions, respectively. The maximum tolerated infusion time and the serum levels at which the first side-effects appeared, were compared. These maximum doses could be administered to 6 volunteers under TPD, but only to two under medication with the reference preparation. Side-effects under TPD occurred in 5, after infusion of the reference preparation in 9 volunteers. Serum levels of theophylline at the end of the infusion period reached (14.6 +/- 4.21 (TPD) and 23.01 +/- 6.02 mg/l (TE), respectively. The average infusion time for the test preparation was 54.8, for the reference preparation 46.2 min. The average serum theophylline levels of the 5 volunteers with side-effects under TPD reached--when these side-effects occurred --11.26 +/- 4.52 mg/l; the same volunteers showed after administration of TE levels of 14.94 +/- 7.49 mg/l. Our results showed an approx. additive effect of the side-effects together with an--according to literature--over-additive pharmacological effect of the single components of TPD.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4039590 TI - A new slow-release form of 5-aminosalicylic acid for the oral treatment of inflammatory bowel disease. Biopharmaceutic and clinical pharmacokinetic characteristics. AB - A new enteric coated form of 5-aminosalicylic acid (5-AS, Salofalk) for the treatment of inflammatory bowel disease was developed. In 11 hospitalized patients with Crohn's disease or ulcerative colitis the steady-state pharmacokinetics of 5-AS and its major metabolite, N-acetyl-5-AS (Ac-5-AS), was investigated. During treatment with 0.5 g 5-AS tid elimination half-life (t 1/2) ranged from 0.7 to 2.4 h (1.4 +/- 0.6 h, mean +/- SD; n = 6) and mean steady state plasma levels (Css) of 5-AS and Ac-5-AS averaged 0.7 +/- 0.4 micrograms/ml and 1.2 +/- 0.3 micrograms/ml, respectively. Treatment with the smaller dose of 0.25 g 5-AS tid (n = 5) resulted in a shorter t 1/2 (0.6 +/- 0.2 h), lower Css for 5-AS (0.4 +/- 0.2 micrograms/ml) and Ac-5-AS (1.0 +/- 0.2 micrograms/ml). Urinary and fecal recovery of total 5-AS was calculated to 44 +/- 21% and 35 +/- 10%, respectively. Both compounds were slightly bound to plasma proteins (5-AS: 43%, Ac-5-AS: 78%). In conclusion, the present data would suggest that the new oral dosage form delivers sufficient amounts of therapeutically active 5-AS for local and systemic action in patients with inflammatory bowel disease. PMID- 4039591 TI - [The pharmacokinetics of josamycin]. AB - Determination of the distribution coefficients in vitro demonstrates that josamycin (Wilprafen) is at least 15 times more lipophilic than erythromycin. On the other hand the distribution coefficients of penicillin G and of amoxicillin be in the hydrophilic range. The serum protein binding of josamycin is 15%, which is markedly less than with the other macrolides. These in vitro experiments show that small structural differences can alter the physicochemical and biological behaviour of an antibiotic, even when the molecules are closely related. A cross over experiment with 12 volunteers and multiple application of 1 g of josamycin base or 1.175 g of erythromycin ethyl succinate showed that both macrolides are rapidly absorbed and reach their maximum within the first hour. In 21 patients the concentration of josamycin in lung tissue was 2 to 3 times that in the blood. The highest concentration of josamycin reached was 3.68 micrograms/g lung tissue (mean of 12 patients) and this was found for the group of patients from whom the tissue samples had been taken 2-3 h after the last administration of the drug. Lower mean concentrations of erythromycin were found in the serum and lung tissue of a similar group of 31 patients. The results indicate that the new macrolide antibiotic josamycin accumulates well in lung tissue and that the concentrations necessary for the treatment of infections (minimal inhibitory concentrations [MIC]) are rapidly reached also in the tissue. PMID- 4039592 TI - Studies on the pharmacokinetics of fluorescein and its dilaurate ester under the conditions of the fluorescein dilaurate test. AB - Some aspects of the pharmacokinetics of fluorescein have been studied under the conditions of the fluorescein dilaurate test (Pancreolauryl-Test) in healthy volunteers. Dependence of fluorescein excretion on urine volume was investigated in a retrospective study in 370 patients. For intravenously administered fluorescein mean Cmax was 10.9 micrograms/ml with a mean elimination half-life of 286 min. For orally administered fluorescein sodium mean Cmax was 3.5 micrograms/ml with a tmax of 120 min and a t 1/2 of 267 min. Bioavailability of fluorescein by oral administration was 99%. By contrast, fluorescein from fluorescein dilaurate showed a 56% bioavailability under the conditions of the test with a Cmax of 1.8 micrograms/ml, a tmax of 270 min and a tt 1/2 of 246 min. Following enteral absorption of fluorescein hepatic extraction and enterohepatic circulation via the bile occurs, but although the concentrations of fluorescein in the bile may exceed those in the urine the absolute amount is likely to be small. In spite of the enterohepatic circulation fluorescein cleared from the urine within 24 h indicating that no delay between Part 1 and Part 2 of the test seems necessary. However, an adequate urine flow must be maintained throughout the test since a renal clearance/urine flow relationship exists, with fluorescein excretion being increased with increasing urine volume. PMID- 4039593 TI - Soybean protein diets in the management of type II hyperlipoproteinaemia. AB - The efficacy of soybean protein treatment of stable type II hyperlipoproteinaemia was evaluated in 57 patients assigned to the following protocols: (i) substitution of animal protein with soybean protein (19 subjects) and (ii) addition of soybean protein to a standard low-lipid diet (38 subjects). After 16 weeks of treatment, plasma cholesterol was reduced by 29.5% in the first group, and by 29.9% in the second; the difference was not significant. Similarly the reduction in LDL cholesterol was not significantly different between the 2 groups (39% in the first group and 36% in the second). Plasma triglycerides fell by 11.8% and 18.2%, respectively. HDL cholesterol was not modified to any significant extent by soybean protein regimens. These results provide that the addition of soybean protein to a standard low-lipid diet is effective in inducing a significant cholesterol decrease in patients with type II hyperlipoproteinaemia. PMID- 4039594 TI - Headache in an elderly woman. PMID- 4039595 TI - Longitudinal brainstem axons mediating circling: behavioral measurement of conduction velocity distributions. AB - Current applied near the midline brainstem elicits rapid ipsiversive circling. Pontine and midbrain sites were stimulated concurrently with paired pulses and the number of pulse pairs required to produce 3 complete circles in 10 s was measured at various intrapair (C-T) intervals. The same results were obtained when C pulses were presented via the midbrain electrode and T pulses via the pontine electrode, or vice versa: as C-T interval increased from 0.4 to 2.0 ms, the number of pulse pairs required decreased gradually. These decreases occurred at longer C-T intervals than the refractory period decreases observed in single electrode tests. These results imply that collision occurred in the directly stimulated axons and that a longitudinal bundle of uninterrupted axons mediates the circling behavior. The sites from which collision was obtained overlap with both medial longitudinal fasciculus and crossed tectobulbar and tectospinal tracts. The axons mediating circling appear to have conduction velocities from 2 to roughly 20 m/s. By comparison, superior colliculus units antidromically driven from contralateral electrode sites that produce circling had conduction velocities from 0.7 to 40 m/s. PMID- 4039596 TI - [Plasma levels of vitamin A and its protein vectors (RBP and PA), carotene, total cholesterol and HDL-cholesterol in healthy adults of the female sex]. AB - Plasma vitamin A, carotenoids, retinol binding protein (RBP), prealbumin (PA), HDL-and total cholesterol were examined in healthy adult females. Plasma levels of vitamin A and carotene were determined by a spectrophotometric method using trifluoroacetic acid, plasma RBP and PA by single radial immunodiffusion, and HDL and total cholesterol by enzymatic colorimetry. Vitamin A and carotene mean values resulted as 43.0 +/- 8.2 micrograms/100 ml and 231.9 +/- 69.0 micrograms/100 ml, respectively. RBP and PA values averaged as 4.2 +/- 1.1 mg/100 ml and 29.4 +/- 6.1 mg/100 ml, respectively; whereas HDL-and total cholesterol were 179 +/- 16 mg/100 ml and 57 +/- 8 mg/100 ml. Vitamin A plasma levels were shown to be significantly related (P less than 0.01) to RBP and PA, but not to the other parameters examined (carotene, HDL-and total cholesterol). PMID- 4039597 TI - [Plasma levels of vitamin A and its protein vectors (RBP and PA), carotene, total cholesterol and cholesterol-HDL in patients with dysplasia of the uterine cervix]. AB - In this study plasma levels of vitamin A, carotenoids, retinol binding protein (RBP), prealbumin (PA), HDL-and total cholesterol were determined in 19 female subjects with cervical dysplasia and compared to those of the healthy female subjects described in our previous research. Plasma levels of vitamin A and carotene were determined by a spectrophotometric method using trifluoroacetic acid, plasma RBP and PA by single radial immunodiffusion and HDL- and total cholesterol by enzymatic colorimetry. Plasma mean values of vitamin A and HDL cholesterol were lower (P less than 0.05 and P less than 0.01, respectively) than in the control group. On the contrary total cholesterol was higher (P less than 0.01) in the patients than in the control group. Vitamin A plasma levels were significantly related (P less than 0.01) to RBP and PA. No significant statistical correlation was found between the severity of the dysplasia and vitamin A plasma levels. PMID- 4039598 TI - [Plasma levels of vitamin A and its protein vectors (RBP and PA), carotene, total cholesterol and HDL-cholesterol in patients with carcinoma of the cervix]. AB - In this study plasma levels of vitamin A, carotenoids, retinol binding protein (RBP), prealbumin (PA), HDL-and total cholesterol of 40 subjects with carcinoma of cervix uteri were determined and compared to those of the healthy female subjects described in our previous research. Plasma levels of vitamin A and carotene were determined by a spectrophotometric method using trifluoroacetic acid, plasma RBP and PA by single radial immunodiffusion, and HDL-and total cholesterol by enzymatic colorimetry. Plasma mean values of carotene, vitamin A, RBP and HDL-cholesterol were lower (P less than 0.01) than in the control group, and the same applies to the PA mean plasma level (P less than 0.05). On the contrary, total cholesterol mean value of the patients resulted to be higher (P less than 0.01) than in the control group. Vitamin A plasma levels were significantly related (P less than 0.01) to RBP and PA. No significant statistical correlation was found between the clinical stage and the histological grading and vitamin A plasma levels. PMID- 4039600 TI - Aztreonam in human serum and breast milk. AB - Serum and milk concentrations of aztreonam were studied in 12 lactating, healthy subjects over the 8 h period after the administration of a single intramuscular or intravenous 1 g dose. Milk concentrations of aztreonam were found to be much lower than serum concentrations at all time points after both routes of injection. Peak milk concentrations of aztreonam averaged less than 1% of peak serum concentrations. Times to peak concentrations averaged 6 and 10 times longer in milk than in serum after intramuscular and intravenous injections, respectively. The low milk levels, as well as the previously determined poor oral absorption of aztreonam, suggest a low risk of untoward effects in the nursing infant. PMID- 4039599 TI - Tinidazole milk excretion and pharmacokinetics in lactating women. AB - Five women undergoing acute Caesarean section were given an i.v. dose of 1600 mg tinidazole preoperatively as prophylaxis against anaerobic infection. Blood and breast milk samples were collected at 8 and 4 h intervals, respectively, for 120 h. Tinidazole concentrations were measured by means of high performance liquid chromatography (h.p.l.c). The concentration of tinidazole in breast milk was highly related to the concentration in serum (r = 0.969). Tinidazole concentrations in serum declined monoexponentially with an average half-life of 11.4 h (range 8.7-13.1). The milk/serum concentration ratio varied between 0.62 and 1.39. Seventy-two hours after the Caesarean section the milk concentration exceeded 0.5 microgram/ml in only one woman. It may be calculated that at this time the maximum daily dose to the infant would be 0.1 mg/kg body weight (assuming 3.5 kg body weight and 400 ml milk consumed). We conclude that until tinidazole has been proven harmless to the neonate breast feeding following i.v. administration of 1600 mg should not be initiated earlier than 72 h after the dose. PMID- 4039601 TI - Retinal function of the diabetic retina after argon laser photocoagulation assessed electroretinographically. AB - Electroretinographic (ERG) responses were measured in diabetic patients before, during, and after panretinal photocoagulation treatment with argon laser. The laser applications reduced considerably the amplitudes of the a and b waves of the ERG. Moreover, the relationship between the amplitude of the b wave and that of the a wave was severely affected, resulting in ERG responses of abnormal pattern. The b waves were smaller than expected from the a waves. These findings indicated that the photocoagulation treatment not only destroyed the retinal areas directly illuminated by the laser beam, but also affected the functional integrity of adjacent areas. These additional effects resulted in subnormal signal transmission from the photoreceptors to the proximal retina. PMID- 4039602 TI - Biodehalogenation: reactions of cytochrome P-450 with polyhalomethanes. AB - The products, stoichiometry, and kinetics of the oxidation of the enzyme cytochrome P-450 cam by five polyhalomethanes and chloronitromethane are described. The reactivity of the enzyme is compared with that of deuteroheme and with the enzyme in its native cell, Pseudomonas putida (PpG-786). In all cases, the reaction entails hydrogenolysis of the carbon-halogen bond: 2FeIIP + RCXn--- 2FeIIIP + RCHXn-1 (P = porphyrin or P-450 cam in vitro and in vivo). Trichloronitromethane was the fastest reacting substrate, and chloroform was the slowest. The results establish that P. putida is a valid whole cell model for the reductase activity of the P-450 complement in these reactions. The reactions of cytochrome P-450 with polyhaloalkanes proceed in a manner quite analogous to other iron(II) proteins in the G conformation. The chemistry observed for the enzyme parallels that of its iron(II) porphyrin active site. Iron-bonded carbenes are not intermediates, and hydrolytically stable iron alkyls are not products of these reactions. PMID- 4039603 TI - Adducts of the antitumor drug cis-diamminedichloroplatinum(II) with DNA: formation, identification, and quantitation. AB - Salmon sperm DNA, treated with the antitumor agent cis diamminedichloroplatinum(II) (cis-DDP), was enzymatically degraded to (oligo)nucleotides. Four Pt-containing products were identified by 1H NMR after preparative chromatography on a diethylaminoethyl-Sephacel column at pH 8.8. In all identified adducts, comprising approximately 90% of the total Pt in the DNA, Pt was linked to the N7 atoms of the nucleobases guanine and adenine. The two major adducts were cis-Pt(NH3)2d(pGpG) and cis-Pt-(NH3)2d(pApG), both derived from intrastrand cross-links of cis-DDP on neighboring nucleobases. Only the d(pApG) but not the d(pGpA) adduct could be detected. Two minor adducts were Pt(NH3)3dGMP, resulting from monofunctionally bound cis-DDP to guanine, and cis Pt(NH3)2d(GMP)2, originating from interstrand cross-links on two guanines as well as from intrastrand cross-links on two guanines separated by one or more bases. For analytical purposes we developed an improved method to determine cis-DDP adducts. Routinely, 40-micrograms samples of enzymatically degraded cis-DDP treated DNA are now analyzed by separation of the mononucleotides and Pt containing (oligo)nucleotides on the anion-exchange column Mono Q (FPLC) at pH 8.8 (completed within 14 min) and subsequent determination of the Pt content in the collected fractions by atomic absorption spectroscopy. The method was used to optimize the digestion conditions for cis-DDP-treated DNA. In kinetic studies on the formation of the various adducts, a clear preference of the Pt compound to react with guanines occurring in the base sequence d(pGpG) was established. PMID- 4039604 TI - Isolation and characterization of monkey interphotoreceptor retinoid-binding protein, a unique extracellular matrix component of the retina. AB - The interphotoreceptor retinoid-binding protein (IRBP) has been isolated from monkey interphotoreceptor matrix (IPM). Following gentle washing of the IPM from the retinal surface, the protein was purified to homogeneity by concanavalin A Sepharose affinity chromatography, ion-exchange high-performance liquid chromatography (HPLC), and size-exclusion HPLC. Bovine IRBP was purified similarly and compared with the monkey protein. Sedimentation equilibrium analysis yielded a molecular weight of 106 000 +/- 2900 for the native monkey protein. Sedimentation velocity analysis gave a sedimentation coefficient of 5.4 +/- 0.3 S and a frictional ratio of 1.59, indicating an asymmetrical molecular shape. IRBP contains neutral sugar, including fucose, and sialic acid; the glycoprotein nature of the proteins probably accounts for the microheterogeneity observed in the electrofocusing pattern of both bovine and monkey IRBP. Both IRBPs have isoelectric points between 6.0 and 7.0. The fluorescence emission lambda max of the bound ligand was 470 nm with excitation at 340 nm, while the excitation lambda max was 333 nm with emission at 470 nm, for monkey IRBP incubated with exogenous all-trans-retinol. The amino acid compositions of the monkey and bovine proteins are similar; nonpolar amino acids account for over 50% of the residues, which may explain the apparent hydrophobic nature of the isolated proteins. The amino-terminal analyses indicated considerable homology between the monkey and bovine IRBPs in this region and verified the purity of the isolated proteins. IRBP thus appears to be a unique, conserved glycoprotein of the retinal extracellular matrix that could serve as a retinoid-transport vehicle. PMID- 4039606 TI - Influence of cholesterol and prostaglandin E1 on the molecular organization of phospholipids in the erythrocyte membrane. A fluorescent polarization study with lipid-specific probes. AB - Anthryl-labeled fluorescent probes closely mimicking phosphatidylcholine and sphingomyelin were applied to study the state of these phospholipids in the rabbit erythrocyte membrane. At normal cholesterol levels both probes exhibited higher fluorescence polarization values in the membranes than in phospholipid vesicles of similar lipid composition, indicating a decreased fluidity of the probe environment in erythrocyte ghosts. In ghosts prepared from normal erythrocytes no evidence of lateral separation of phosphatidylcholine and sphingomyelin was found. At higher cholesterol levels, however, these lipids appear to segregate. Probably the effect of cholesterol on the erythrocyte membrane lipids involves lipid-protein interactions. At physiological concentrations, prostaglandin E1 only weakly affects the state of phosphatidylcholine and sphingomyelin in erythrocyte membranes. Cholesterol enrichment amplifies the effect of prostaglandin E1. Although the prostaglandin E1-induced changes depended much upon whether the ghosts were enriched with cholesterol in vitro or in vivo, with both types of ghosts effects of prostaglandin E1 were seen at extremely low effector concentrations that may have presented a few molecules of prostaglandin per ghost. The structural and functional significance of these findings is discussed. PMID- 4039605 TI - One-step immunoaffinity purification of active progesterone receptor. Further evidence in favor of the existence of a single steroid binding subunit. AB - A very high capacity immunoaffinity matrix for the purification of progesterone receptor was prepared by cross-linking a monoclonal antireceptor antibody to protein A-Sepharose through the Fc fragment. The monoclonal antibody was selected for its property of losing affinity for the receptor at pH 10.5, i.e., in conditions where the receptor remains stable for extensive periods of time. This made it possible to elute active receptor form the immunosorbent. From crude rabbit uterine cytosol the steroid-receptor complexes were purified in a single step. A 1-mL column (containing 7 mg of monoclonal antibody) bound 1600 pmol of steroid-receptor complexes of which 79.5% were eluted. The overall yield of purification was 49%. The specific activity of the purified steroid-receptor complexes was 6.71 +/- 0.79 nmol of bound steroid/mg of protein (mean +/- SE of four experiments). The purified receptor consisted of a mixture of 110 000- and 79 000-dalton forms. The latter appeared to be produced by proteolysis of the larger form during purification since immunoblot experiments showed that, at the start of purification, the 110 000-dalton form was present in overwhelming majority (80-95%) in the uterine cytosol and that the 79 000-dalton form only appeared during purification. This conclusion was also supported by the peptide analysis of both forms of receptor: the purified receptor was denatured and labeled with 125I; the 110 000- and 79 000-dalton forms were isolated by gel electrophoresis in denaturing conditions and electroelution and were then submitted to mild or extensive digestions by trypsin, chymotrypsin, and protease V8 from Staphylococcus aureus.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4039607 TI - The quantitative determination of metabolites of 6-mercaptopurine in biological materials. VI. Evidence for posttranscriptional modification of 6-thioguanosine residues in RNA from L5178Y cells treated with 6-mercaptopurine. AB - Mammalian cells incorporate 6-thioguanosine into their nucleic acids when grown in the presence of 6-mercaptopurine. 35S-labeled total RNA was prepared from L5178Y murine lymphoma cells grown in vitro in the presence of 6 [35S]mercaptopurine. Base analyses of this RNA suggested that 6-thioguanosine residues in RNA molecules undergo posttranscriptional modification. Thus, enzymatic peak-shifting analyses using anion-exchange high-performance liquid chromatography were applied to the hydrolysis products released from total RNA preparations by digestion with nuclease P1 or nuclease P1 plus nucleotide pyrophosphatase. At least eight 35S-labeled, phosphatase-sensitive compounds structurally different from [35S]6thioGMP were found in nuclease P1 digests. Four of these compounds were susceptible to cleavage with nucleotide pyrophosphatase, thus indicating that they contained phosphoric acid anhydride bonds. Individual RNA species were not separately examined, the radiochromatographic data, however, which were obtained from digests of total RNA preparations, present evidence that 6-thioguanosine 5'-diphosphate and 6-thioguanosine 5'-triphosphate exist as 5' terminal starting nucleotides (in tRNA and rRNA) and that 6-thioguanosine becomes incorporated into the highly modified dinucleoside triphosphate structures (caps) which commonly block the 5'-termini of eukaryotic poly(A)+ mRNA-molecules. PMID- 4039608 TI - Phospholipid fatty acids in brains of normal sheep and sheep with ceroid lipofuscinosis. AB - The ceroid-lipofuscinoses are a group of inherited diseases of humans and animals characterised by brain atrophy and the storage of a fluorescent lipopigment. Brain grey matter phospholipid fatty acids of diseased sheep are compared with those of normal sheep. Phosphatidylethanolamine of diseased sheep contains more 18:1(n-9) and less 22:6(n-3) than normal and their phosphatidylcholine less 16:0. Other differences are minor. All differences are in the same direction as those reported for the infantile form of human ceroid-lipofuscinosis, but are smaller. Normal sheep grey matter phosphatidylinositol contains 8.5% 20:4(n-6) and 24.6% 22:6(n-3), in contrast to 28.5 and 4.6%, respectively, in humans. The other sheep phospholipids have similar fatty acid profiles to those from humans. Apart from low levels of 20:3(n-9) and 22:3(n-9) they contain no additional non-essential fatty acid derived species. No sign of essential fatty acid deficiency occurs in either diseased or normal sheep. It is concluded that sheep must conserve their restricted essential fatty acid supply for structural functions, and that an abnormality in fatty acid metabolism is not primarily involved in the pathogenesis of ceroid-lipofuscinosis. The results also call into question the primary role of peroxidation of polyunsaturated fatty acids in lipopigment formation in this disease. PMID- 4039609 TI - Study of the luteinizing hormone-induced increase of ovarian blood flow during the estrous cycle in the rat. AB - CYF rats were anesthetized on various days of the 4-day cycle and blood samples were collected at 5-min interals from the ovarian vein before and after i.v. administration of 5 micrograms/100 g BW of luteinizing hormone (LH). Ovarian venous outflow, blood pressure and hematocrit were continuously recorded, and from the blood samples progesterone (P) and 17 beta-estradiol (E2) were determined by radioimmunoassay (RIA). Ovarian blood flow and P secretion showed a parallel increase on Day 1 (estrus), on Day 2, and on the afternoon of Day 4 (proestrous). LH increased ovarian blood flow each day of the cycle together with P and E2 secretion; however, no relationship was seen between the initial value of hormone secretion and the LH-induced increase of ovarian blood flow. Inhibition of hormone secretion by cycloheximide prevented the LH-induced increase of ovarian blood flow; moreover, a decrease in ovarian blood flow parallel with the diminution of hormone secretion was observed. Indomethacin pretreatment abolished the hyperemic effect of LH and partially inhibited the LH induced increase of hormone secretion. Propranolol blocked the LH-induced increase of ovarian blood flow and blunted the effect of LH on hormone secretion. It was concluded that in LH-induced hyperemia, cAMP, prostaglandins and other vasoactive metabolites released during the process of hormone synthesis, and also a beta-adrenergic mechanism, are involved in the regulation of ovarian blood flow. PMID- 4039610 TI - Effect of dietary restriction on estrous cyclicity and follicular reserves in aging C57BL/6J mice. AB - Restricting the food intake of female mice by alternating days of feeding and fasting delayed the age-related loss of estrous cycling potential and retarded the rate of follicular depletion, as determined after reinstatement of ad libitum (AL) feeding. During the period of food restriction (FR; 3.5-10.5 mo), food intake and body weight were about 80% of AL values. Mice were acyclic and predominantly in a state of diestrus during FR, but after reinstatement of an AL diet at 10.5 mo all FR mice resumed cycling regularly. By contrast, 80% of AL controls had become acyclic by this age, and the cycles of the remaining mice were significantly longer than those of the reinstated FR mice. Follicular reserves of 12.5-mo-old FR mice were twice those of age-matched AL controls. Cycling performance of reinstated FR mice, measured by cycle length and the proportion of mice still cycling, was equivalent to that of AL mice when the latter were 2-5 mo younger. Ovarian age, measured by the size of the follicular reserve, was similarly retarded in FR mice. Based on these data and previous evidence that follicular depletion plays a major role in the cessation of cyclicity in this strain, we hypothesize that the delayed loss of estrous cyclicity in aging FR mice is mediated at least in part by the retarding effect of dietary restriction on the rate of follicular depletion. PMID- 4039611 TI - Enhanced plasminogen-activator production by leukocytes in the human and murine Chediak-Higashi syndrome. AB - We have studied the coagulation status of eight patients with the Chediak-Higashi syndrome (CHS), both in the chronic and the accelerated phase of the disease. It has been shown that during the accelerated phase there are coagulation abnormalities. These abnormalities include a peripheral thrombocytopenia, minor alterations of liver clotting factors, and mainly a profound hypofibrinogenemia and hypoplasminogenemia, which cause life-threatening bleedings. These disorders are of complex origin, but a fibrinolytic process, possibly primary, appears to play a significant role, since the present evidence for intravascular coagulation is not definitive. The accelerated phase of the CHS is characterized by a visceral infiltration by macrophages and lymphocytes. Therefore, we have investigated the possible role of the macrophages in the fibrinolytic process. We have found an excessive plasminogen activator (PA) production by CHS mononuclear cells in the accelerated phase and to a lesser extent in the chronic phase, except in one patient in whom no anomaly was found. Single-cell studies revealed an increased number of PA-producing cells among the monocyte-macrophage lineage rather than a higher level of production per cell. Polymorphonuclear cells (PMN) from patients with CHS were also shown to contain more PA. Slight but significant abnormalities in PA production were observed in obligatory heterozygotes (five out of nine), indicating the inherited nature of the excessive PA production. Finally, an enhanced PA production was similarly demonstrated using beige mice macrophages. The exacerbated production of PA by macrophages in the accelerated phase of the CHS can account to some extent for the coagulation abnormalities that have been observed. PMID- 4039612 TI - The lipid composition of bovine sebum and dermis. PMID- 4039613 TI - Artificial infection of ticks with Theileria annulata. PMID- 4039614 TI - Protozoal diseases of camels. PMID- 4039615 TI - Dose effects of naloxone on fixed morphine dependence: simultaneous behavioral and 2-deoxyglucose study in the rat. AB - We have simultaneously studied regional cerebral glucose utilization (RCGU) and behavior during naloxone precipitated morphine withdrawal. For RCGU studies, 25 brain regions were analyzed that previously had been shown to participate in morphine withdrawal. Four established behavioral signs of morphine withdrawal were recorded: wet shakes, jumping, weight loss, and autonomic signs. Using a 10(4) range of naloxone dose (0.0005-5.0 mg/kg), dose dependent effects were found for 3 behaviors: jumping, weight loss and autonomic signs. The incidence of wet shakes did not correlate with naloxone dose. Increases in RCGU in several specific brain sites were also naloxone dose dependent. Naloxone dose dependent increases in RCGU during precipitated morphine withdrawal may be divided into 3 classes of responses: Class I structures (paraventricular, ventromedial, and lateral hypothalamus) exhibited their largest RCGU increases between 0.005 and 0.05 mg/kg of naloxone; Class II structures (preoptic areas, basal ganglia, anterior and intralaminar thalamic nuclei, mammillary nuclei, and certain midbrain regions) showed gradual RCGU increases across the 10(4) range of naloxone dose; and, Class III structures (diagonal band, medial and lateral septum, and the central amygdaloid nucleus) displayed large RCGU increases across 0.5-5.0 mg/kg of naloxone. Regression analysis of RCGU vs behavior showed correlations between Class I responses and autonomic signs (P less than 0.010); weight loss was correlated with all 3 classes of naloxone dose dependent RCGU responses during withdrawal (P less than 0.05). The strong positive correlation among these RCGU increases and certain morphine withdrawal behaviors supported the use of RCGU measurements in specific brain sites as a sensitive and objective biochemical indicator of the presence and severity of morphine dependence. In addition, this study demonstrates that changes in RCGU in different brain regions are heterogeneous with respect to naloxone dose and appear reproducibly along a continuum from mild to severe withdrawal. PMID- 4039616 TI - The cortico-medial amygdala in the central nervous system organization of agonistic behavior. AB - Previous studies suggested that the corticomedial amygdala is involved in agonistic behavior by affecting social learning processes. The present study shows that deficits in the avoidance of a dominant male rat conditioned by defeat were only observed after bilateral lesions restricted to the medial amygdala and not after destroying the cortical portion. These results are related to the specific afferent and efferent connections of the medial amygdala with other brain structures involved in the control of agonistic behavior. Within the corticomedial amygdala the medial amygdaloid nucleus was found to be a major recipient of afferents from the accessory olfactory bulb, but also a source of efferent projections to the ventrolateral aspects of the ventromedial hypothalamic nucleus and the ventral premammillary nucleus. A strong reciprocity exists in the connections between ventromedial hypothalamus and premammillary nuclei with the medial amygdala. The connections between the ventromedial hypothalamic and dorsal premammillary nucleus with the midbrain periaqueductal grey suggest an important role for the periaqueductal gray in the descending output in the anatomical substrate for agonistic behavior. PMID- 4039617 TI - Ontogeny of striatal unit activity and effects of single or repeated haloperidol administration in rats. AB - Development of striatal unit activity recorded from chloral hydrate anesthetized, neonatal rats was characterized electrophysiologically following acute or repeated haloperidol administration. No spontaneously active single units were detected in 8 day old pups. Spontaneous activity was recorded by 17 days of age, although the number of active cells, firing frequency and the variety of firing patterns were less diverse than those observed in 28 day olds. There were also age related differences in striatal unit responses to haloperidol. A significant increase in activity was induced by acute haloperidol administration only in 28 day old animals. No tolerance to the acute effects was demonstrated. Both 17 and 28 day olds responded to repeated haloperidol injections, followed by a 24 h recess, with an increase in striatal activity. These results may assist our understanding of the effects of human fetal, neonatal and/or adolescent exposure to neuroleptics. PMID- 4039618 TI - Effect of duration of haloperidol treatment on DA receptor supersensitization in aging C57BL/6J mice. AB - Apomorphine-induced behavior, striatal [3H]spiperone binding, and striatal choline acetyltransferase (ChAT) activity were assessed in 6 1/2, 13, and 27-30 month-old male C57BL/6J mice following 0, 30, 60 or 90 days treatment with the dopaminergic (DA) antagonist haloperidol. Both apomorphine-induced behavior and [3H]spiperone binding (Bmax) increased linearly with duration of haloperidol treatment, with no detectable age difference in the degree of supersensitization, although basal receptor density declined with age. Middle- and old-aged mice showed prolonged stereotypic behavior relative to young mice, suggesting slower apomorphine clearance. No differences in ChAT activity were detected with either age or duration of haloperidol treatment. Although the group means of binding and behavior were highly related, the within group correlations were poor. Overall, the results suggest that aged animals are capable of DA receptor supersensitization when given a sufficient stimulus--in this case, relatively long treatment regimes. Previously reported deficits in neuroleptic-induced supersensitization in old mice may be confined to relatively short treatment periods at low doses. PMID- 4039619 TI - Phosphorylation of the postsynaptic density glycoprotein gp180 by endogenous tyrosine kinase. AB - Incubation of postsynaptic densities (PSDs) with [gamma-32P]adenosine triphosphate (ATP) results in the phosphorylation of a number of proteins. Of these, phosphoproteins with apparent molecular weights (Mr) of 51,000, 180,000, 300,000, 320,000 and 370,000 contain 32P which is resistant to digestion with hot KOH suggesting the presence of [32P]phosphotyrosine residues. Phosphoamino acid analysis of total 32P-labelled PSDs identified [32P]phosphotyrosine as well as phosphoserine and phosphothreonine as products of the phosphorylation reaction. The PSD-specific glycoprotein gp180 was isolated from 32P-labelled PSDs and shown to contain [32P]phosphotyrosine. The results identify tyrosine kinase as a component of purified PSDs and gp180 as an endogenous substrate for this enzyme. PMID- 4039621 TI - Similar functional anatomy of spontaneous and precipitated morphine withdrawal. AB - The distribution and magnitude of changes in regional cerebral glucose utilization were similar whether opiate withdrawal was spontaneous or naloxone induced. PMID- 4039620 TI - Effects of phencyclidine administration on behavior and brain neurotensin-like immunoreactivity in rats. AB - The effects of acute and chronic phencyclidine (PCP) administration on neurotensin-like immunoreactivity (NTLI) were investigated in discrete regions of rat brain. Both acute and chronic administration of PCP induced high locomotor activity, stereotypy and ataxia. On PCP administration, NTLI decreased significantly in the frontal cortex (Fc) alone. These results suggest that the decrease in NTLI in Fc is related to the behavioral abnormalities produced by PCP. PMID- 4039622 TI - Neonatal brain damage and recovery: intraventricular injection of NGF at time of injury alters performance of active avoidance. AB - Rats were given lesions of either the ventromedial hypothalamus (VMH) or septal nucleus at 7 days of age and then were tested repeatedly in an active avoidance task (A.A.) from 20 to 80 days. VMH rats were consistently impaired on the A.A. task beginning at 40 days of age. The animals with septal lesions performed the A.A. task consistently better than VMH or control animals throughout the entire test period, the septal syndrome becoming more pronounced as the rats reached maturity. In intact rats a single, intraventricular injection of NGF given at 7 days of age resulted in a greater reactivity, especially as the rats approached maturity. NGF, given at time of surgery, also improved performance of the A.A. task in VMH-damaged rats tested at 40-80 days. In rats given septal lesions, NGF treatment at time of injury attenuated the septal syndrome of improved A.A. performance. The data indicate that NGF treatment, given to neonatal rats, can produce long-lasting effects on CNS functions and can contribute to functional recovery from brain lesions. PMID- 4039623 TI - [Pseudoparalysis induced by cancer chemotherapy (cis-platinum)]. PMID- 4039624 TI - Cryptosporidiosis: a cause of summer diarrhea in children. AB - Recent studies have suggested that some outbreaks of diarrhea in children may be caused by Cryptosporidium, a parasite associated with gastrointestinal and respiratory tract infection in animals. In a study of 7300 British Columbia patients with diarrhea, cryptosporidial oocysts were found in the stool samples of 46 (0.63%). It appears that the occurrence of cryptosporidiosis is related to three factors: the patient's age, the time of year and the geographic location. PMID- 4039625 TI - Doxorubicin plus cisplatin in the treatment of apudomas. AB - Twelve patients with advanced apudomas--six with carcinoid tumors, two with chemodectomas, two with pancreatic islet cell tumor, and one each of medullary carcinoma of the thyroid and paraganglioma of unknown primary--were treated with a combination of doxorubicin 50 mg/m2 and cisplatin 50 mg/m2 every 3 to 4 weeks. Biochemical markers were present in 8 of the 12 patients. Five of the 12 patients (3 with carcinoid and 2 with chemodectomas) responded with more than 50% regression of tumor size measured as hypothetical area. Three others (two with islet cell tumors and one with carcinoid) had clinical and/or biochemical improvements. A median duration of response was 6 months. Nausea, vomiting, and alopecia were universal. Mild or moderate leukopenia was the most frequent toxicity. No sustained nephrotoxicity was seen. The combination of doxorubicin and cisplatin provides a new palliative therapy for patients with APUD tumors. PMID- 4039626 TI - Multimodal approach (surgery, chemotherapy, and radiotherapy) in the treatment of advanced ovarian carcinoma. AB - Forty-five patients with advanced ovarian carcinoma without prior chemotherapy were treated with cisplatin-Adriamycin (doxorubicin) combination, 50 mg/m2 intravenously, for 11 cycles. Second-look operation (SLO) was performed in patients without evidence of disease at the end of chemotherapy. Abdominopelvic irradiation was administered to those found to have microscopic or minimal disease (tumor less than 2 cm) at SLO. Forty patients were evaluable. Chemotherapy induced complete response in 56.7% and partial response in 16.7%. In 25% of the reoperated patients, no tumor was found; 30% had microscopic disease; 25% had minimal disease; and 20% had larger tumors. Two-year survival rate was 45%. The residual tumor left at initial operation, the histologic grade, and the response to chemotherapy influenced survival. Toxicity was moderate. There were three treatment-related deaths (one due to sepsis, one due to cardiotoxicity, and one at SLO, respectively). Radiotherapy was poorly tolerated after chemotherapy. The median duration of follow-up was 21.5 months. Further follow-up is needed to study the long-term benefits of this multimodal approach. PMID- 4039627 TI - Is cytoplasm intelligent too? PMID- 4039628 TI - Cisplatin in the treatment of advanced gastric carcinoma: a phase II study. AB - Twenty-one patients with advanced local or metastatic gastric carcinoma were treated with 75 mg/m2 of cisplatin every 3 weeks. Six patients had received no prior chemotherapy. One patient achieved complete tumor regression lasting 5 months, while three patients had partial responses of 2, 4, and 11 months' duration, respectively, resulting in an overall response rate of 18% (95% confidence limits: 5%-40%). All four responding patients had improvement in performance status. Two of six patients who had had no prior chemotherapy responded, while only two of 16 patients previously treated with 5-FU and doxorubicin responded. PMID- 4039629 TI - Cisplatin neurotoxicity: failure to demonstrate vitamin B12 inactivation. AB - Cisplatin binds in vitro with vitamin B12 coenzymes at physiologic pH and temperature. We have hypothesized that cisplatin-induced neurotoxicity is due to an in vivo inactivation of the cobalamin coenzymes. Vitamin B12 metabolism was studied in patients treated with cisplatin for advanced cancer. Serum levels of B12 and B12-binding capacity remained normal during cisplatin therapy. Excessive urinary excretion of methylmalonic acid and homocystine, which are both metabolic correlates of cellular cobalamin deficiency, was not demonstrated after cisplatin administration. Thus, we find no evidence to implicate cellular B12 deficiency as a mechanism of cisplatin neurotoxicity. PMID- 4039630 TI - Muscle fiber disarray in patients without hypertrophic cardiomyopathy. AB - Muscle fiber disarray (MFD) has been described as the histologic feature of hypertrophic cardiomyopathy (HC), but it was also found in normal and other abnormal conditions. Its distribution related to the topography of the myocardium has not been described. In this paper, the incidence of MFD in hearts free from HC, the frequency of the histologic disorganization and the affected muscles involved were studied at autopsy. 29 hearts with acute myocardial infarction and 1 with suppurated myocarditis were employed. Macroslides containing the point of maximum septal enlargement were selected for histological examination. The areas of MFD were measured by a polar planimeter and correlated with the involved wall, the total slice area, parietal widths and involved muscles. 27 patients (90%) presented with MFD; hypertrophic ventricular walls were observed in 10, 8 of which had MFD. The remaining 20 patients with nonhypertrophic ventricular walls had MFD in 19 instances. There was septal posterior involvement in 26 cases (p less than 0.0005). 12 patients (44.4%) had only one wall involved. Only 1 patient presented more than 5% of MFD in regard to the total area. The septal wall was the most affected (p less than 0.0005). The most commonly affected muscle was the deep-sinospiral, either alone or combined with other muscles (p less than 0.01). Greater MFD was found (23/30) in patients with septum/posterior wall ratio less than 1.3 cm. It is concluded that MFD may affect up to 10% of the septum in patients free from HC, and that secondary hypertrophy is not a prerequisite for MFD.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4039631 TI - Endocrine control of thymic serum factor production in young-adult and old mice. AB - The influence of different endocrinological manipulations on the blood concentration of serum thymic factor (FTS) was studied in young-adult and old mice. Among the experimentally induced endocrinopathies in youth, hypothyroidism and diabetes caused strong reductions of FTS levels, which were restored to normal by the appropriate hormonal substitutive therapy. Removal of adrenals or gonads has no significant effect on FTS level. Old mice, which show undetectable levels of FTS and low levels of thyroxine, can regain the capacity to produce FTS, provided they are treated with thyroxine. The variations of FTS blood levels in the course of endocrinological manipulations were due to a direct or indirect effect exerted on the recipient thymus. Hormonal treatment of thymectomized mice did not induce any FTS-like activity in their sera, nor did hormones interfere in vitro with the bioassay used to test for FTS. These data suggest that the neuroendocrine balance modulates the synthesis and/or the release of FTS from the thymus during the whole life of the organism and that the decline of FTS production with advancing age is largely dependent on age-associated endocrinological imbalances. PMID- 4039632 TI - Cleavage in a saponin model of the sea urchin egg. AB - A cell model, in which cleavage could be induced, was obtained from fertilized sea urchin eggs by putting eggs that were in the first cleavage into a solution containing 3 X 10(-5) g/ml saponin and suitable amounts of ATP and Ca2+. The cell membrane became freely permeable to ATP and Ca2+ within 1 minute. The respective optimal concentrations of ATP and Ca2+ that advanced the cleavage furrow in this model were 2 mM and 10(-8) M. With the optimal ATP and Ca2+ concentrations, the cleavage furrow of the model advanced at a rate that differed little from that in living eggs. The cleavage furrow soon receded, however, when the concentration of ATP was decreased to less than 1 mM or increased to more than 3 mM, as well as when the concentration of Ca2+ was increased to more than 10(-7) M. PMID- 4039633 TI - Cytochalasin D inhibits the progression from the Go to S phase at the mid prereplicative stage in GC-7 cells stimulated with serum. AB - When the growth of serum-arrested GC-7 cells, a clone from African green monkey kidney, was induced by the addition of 10% calf serum, they began to enter S phase after 15-16 h. When stimulated cells were cultured in the presence of 0.6 micrograms/ml of cytochalasin D, the entrance into S phase was inhibited. Treatment of cells with cytochalasin D during the period earlier than 8 h or later than 11 h after the serum stimulation showed no or little inhibitory effect on the entrance of cells into S phase. Inhibition of the entrance into S phase was observed only when stimulated cells were treated with cytochalasin D during the periods including 9-10 h after stimulation. A rapid increase in protein synthesis occurred 9-12 h after the serum stimulation and was inhibited in the presence of cytochalasin D. These and other results suggested that in the course of the prereplicative process from Go through S phase only the stage around 9-10 h after the start of the cell cycle was sensitive to cytochalasin D and that the block of the cycle was correlated with the inhibition of protein synthesis at this stage. PMID- 4039634 TI - High-dose intravenous metoclopramide and intermittent intramuscular prochlorperazine and diazepam in the management of emesis induced by cis dichlorodiammineplatinum. AB - Intravenous metoclopramide and IM prochlorperazine and diazepam were compared in the management of vomiting occurring during treatment with cis dichlorodiammineplatinum (cis-platinum). A total of 104 cycles in 30 patients were evaluated. Twenty-two patients took part in a cross-over study in which emetic profiles for each patient managed with each anti-emetic schedule were compared. In all, 44 cycles of treatment in 22 patients were evaluated as part of a cross-over study. No significant difference in emetic control was observed between the two anti-emetic regimens. The side-effects observed using IV metoclopramide included extrapyramidal phenomena (19%) and flushing attacks (16%). PMID- 4039635 TI - Cis-dichlorodiammineplatinum (cis-platinum) and etoposide (VP-16) in malignant lymphoma--an effective salvage regimen. AB - Response rates in malignant lymphoma after failure of first-line therapy are generally poor. Twenty-five patients with non-Hodgkin's lymphoma (NHL) unresponsive to standard combination chemotherapy were treated with cis platinum/VP-16. All were heavily pretreated, 29% having received three or more different drug regimens. Seventeen patients were evaluable for response. There were five complete remissions (CR) (29%) and four partial remissions (PR) (24%), giving an overall response rate of 53% (36% of all patients treated). The duration of CR was 12-48 weeks. Median survival for responders was 25 weeks (15 95), compared with only 5 weeks (4-17) for non-responders (P = 0.002). Toxicity included nausea and vomiting, alopecia, minor renal impairment, and myelosuppression. This was sometimes severe: WBC less than 1.0 X 10(9)/l in three patients (18%) and platelets less than 50 X 10(9)/l in five patients (29%). The response rate for this combination is superior to that reported for either cisplatinum or VP-16 alone in similar patients (PR only 26% and 20%-30%, respectively). Further investigation is required to define the role of these drugs in the first-line treatment of poor-prognosis NHL. PMID- 4039636 TI - Assessment of the diurnal variations in urinary homovanillic and vanillylmandelic acid excretion for the diagnosis and follow-up of patients with neuroblastoma. AB - The diurnal variation of urinary homovanillic acid (HVA) and vanillylmandelic acid (VMA) was studied in neuroblastoma patients and in a control group. Urinary HVA and VMA levels in four sequential 6-hour urine collections within a 24-hour period were compared. HVA and VMA levels were expressed in microgram/mg of urinary creatinine (UCr) and in mg/6h specimens. No statistically significant variations between the four time intervals were found when expressed in microgram/mg UCr or mg/6h. The small variations that exist in the excretion of HVA and VMA during different periods of the day are due to variations in renal excretion rather than variations in production. The results from this study indicate that a random urine sample should be as good as a 24-hour collection for diagnosis and follow-up of neural crest tumors. PMID- 4039637 TI - Stability of vitamin A in frozen sera. AB - We compared values for vitamin A measured in fresh sera with values obtained after storage at -20 degrees C for five to eight years. Loss of vitamin A from long-stored sera during the extraction step was eliminated by adding ascorbic acid to the extraction solvent, ethanol. Retinol-binding protein was also measured in the stored sera. Not only did vitamin A values remain stable during the years of storage, but also the correlation between concentrations of vitamin A and retinol-binding protein in the stored sera was typical of that observed with fresh sera. PMID- 4039638 TI - Pattern of human blood spermidine and spermine in prematurity. AB - Blood polyamines have been determined in preterm newborns (24-37 gestation weeks) during the first hours of life and until 20 days after birth. The most elevated polyamine concentrations were found in preterm newborns from the 24th-33rd gestational week. In all preterms, however, polyamine concentrations are higher than in full term newborns. In preterm infants two different patterns of blood polyamines appear in relation to the gestational age: in infants born at 24-34 wk, spermidine reaches the peak at 12 h and spermine shows high concentrations between 12 and 48 h. In infants born at 35-37 wk maximal concentrations of polyamines were reached at 12 h. Successively, in both groups the polyamines progressively decrease up to the 20th day, with some individual variations. Our results may provide a further support to the suggestion of a fetal genesis of polyamines and their involvement in fetal growth. PMID- 4039639 TI - Factors predicting nocturnal hypoxemia in patients with chronic lung disease. PMID- 4039640 TI - The time course of phonological code activation in two writing systems. PMID- 4039641 TI - Why superordinate category terms can be mass nouns. PMID- 4039642 TI - Grammatical priming of inflected nouns by inflected adjectives. PMID- 4039643 TI - "Cognition in music". PMID- 4039644 TI - Vacuolation and infection thread in root nodules of soybean. AB - Profuse vacuolation takes place in the soybean root nodule cells where infection threads carry rhizobia. After the rhizobia are released the disappearance of the infection thread is attributed to its degradation within large vacuoles which result from fusion of small vacuoles. PMID- 4039645 TI - Administration of dazoxiben, a selective thromboxane synthetase inhibitor, in the adult respiratory distress syndrome. AB - Experimental studies suggest that thromboxane A2 could play a role in the pulmonary hypertension of the adult respiratory distress syndrome (ARDS). We therefore investigated the hemodynamic and gasometric effects of dazoxiben, a selective thromboxane synthetase inhibitor, in seven patients who had developed ARDS. The patients were studied for 120 minutes after a single intravenous bolus of 1.5 mg of dazoxiben per kilogram of body weight. During this period, there was no change in pulmonary hemodynamics, a moderate increase in arterial oxygen pressure, and a slight decrease in venous admixture. Therefore, administration of dazoxiben in patients with ARDS does not decrease pulmonary hypertension. This study does not support the role of thromboxane A2 as an important mediator in pulmonary hypertension in human ARDS, at least once the syndrome has been recognized. PMID- 4039647 TI - [Clinical and X-ray features of lung disease in 43 cases in mushroom workers]. PMID- 4039646 TI - The layered organization of nucleosomes in 30 nm chromatin fibers. AB - We have used electron microscopy and established methods of three-dimensional reconstruction to obtain structural information on the 30 nm chromatin fibers from sea cucumber sperm and chicken erythrocytes. The fibers show a longitudinal periodicity of 10-11 nm. We have interpreted this periodicity as due to a grouping of nucleosomes into disks, each disk containing about 5-6 nucleosomes. These disks are closely stacked to form the chromatin fiber. We have built a detailed model for four fibers and we have determined the approximate coordinates of all the nucleosomes in them. The average distance found between neighboring nucleosomes has a value close to 11 nm. They may be connected either as a regularly distorted helix or as a layered zigzag. The second model appears more appropriate, since in the constrictions of the fibers the nucleosomes can only be connected as a zigzag. PMID- 4039648 TI - [Antitumor activity of mixed cis-complexes of platinum(II) with ammonia and cycloalkylamines]. PMID- 4039649 TI - Substitution and primary dependence studies in animals. AB - The mixed agonist-antagonist analgesics buprenorphine, butorphanol, nalbuphine, pentazocine and picenadol were compared to the prototype mu and kappa agonists morphine and Mr 2033, respectively, in the following tests in rhesus monkeys: overt behavioral effects upon acute administration in drug-naive animals; discriminative stimulus properties in monkeys trained to respond to either etorphine or ethylketazocine; self-administration of the test agent relative to codeine; single dose suppression and precipitation in withdrawn and non-withdrawn morphine-dependent monkeys, respectively; and primary addiction studies in drug naive animals. Whereas both buprenorphine and nalbuphine precipitate withdrawal in morphine-dependent monkeys, withdrawal following chronic administration of buprenorphine resulted in no observable signs of abstinence, while nalbuphine withdrawal was similar to that seen in morphine-dependent monkeys. Butorphanol, pentazocine and picenadol all produced mild dependence of the kappa-type; that is, natural withdrawal behavior similar to that seen following chronic Mr 2033 administration. PMID- 4039650 TI - Xorphanol. AB - Xorphanol is a new mixed agonist-antagonist from the morphinan class of analgesics. On the basis of animal experiments, the physical dependence liability of xorphanol is predicted to be of a low order in man. Conceptually, xorphanol is of interest since in vitro experiments have revealed anti-naloxone properties and resistance to antagonism by opioid antagonists. At the practical level, xorphanol is a well tolerated, orally active analgesic that provides effective pain relief clinically. PMID- 4039651 TI - [Polyneuropathy after cisplatin treatment]. AB - Polyneuropathy developed in 7 of 87 women who had been treated with cis-platinum for ovarian carcinoma. Distal disturbances of sensitivity were clinically prominent, the emphasis being on disturbed vibratory perception and acrognosis. No relevant signs of motor dysfunction were noticed, neither clinically nor neurophysiologically. Sural biopsies taken from two women revealed a primary axonal degeneration, mostly affecting the myelinic fibres of large diameter. In 3 cases mild reversion was seen, and in 4 cases no definite reversion, of the disturbed functions - uncertain gait and clumsiness of the hands - during the follow-up period of 6 to 30 months. PMID- 4039652 TI - [Diagnosis of hyperprolactinemia]. PMID- 4039653 TI - Does treatment influence the natural history of patients with hypertrophic cardiomyopathy? AB - Hypertrophic cardiomyopathy is a cardiac disorder of unknown aetiology which is characterised by hypertrophy of a non-dilated left ventricle. The course of hypertrophic cardiomyopathy may be relatively benign, but the risk of sudden death due to ventricular arrhythmias is an important clinical problem. Those patients at greatest risk of sudden death appear to be those with the combination of diagnosis in childhood, a family history of hypertrophic cardiomyopathy and sudden death, and syncopal episodes. The treatment of hypertrophic cardiomyopathy associated ventricular tachycardia with 'conventional' antiarrhythmic agents (disopyramide, quinidine, mexiletine) has seldom been successful. However, treatment of this arrhythmia with amiodarone in well-matched but non-parallel groups of patients has resulted in suppression of arrhythmia and improved survival compared with that seen with 'conventional' antiarrhythmic agents. PMID- 4039654 TI - [Pathogenesis of secretory otitis media]. PMID- 4039655 TI - [A fatal autosomal recessive syndrome with multiple congenital contractures]. PMID- 4039656 TI - The antiprogestin RU38 486: receptor-mediated progestin versus antiprogestin actions screened in estrogen-insensitive T47Dco human breast cancer cells. AB - Despite the theoretical promise of synthetic antiprogestational agents as anticancer agents, experimental tools, midcycle contraceptives, and implantation inhibitors, none has been available for either basic or clinical studies. However, a candidate antiprogestin, RU38 486 [17 beta-hydroxy-11 beta-(4 dimethylaminophenyl)17 alpha-(1-propynl)estra-4,9 -dien-3-one], has recently been described that has antiprogestational and antiglucocorticoid activities in early clinical trials. Its mechanisms of action are unclear. Furthermore, development of this drug underscores an old bioassay problem: that biological screening of progestins and antiprogestins is complex because of the physiological requirement that progestational effects must be superimposed upon an estrogenized system. This has made it difficult to distinguish among progestational, antiprogestational, and antiestrogenic properties of unknown agents. Here we describe the use of T47Dco human breast cancer cells to circumvent these problems. T47Dco cells are rich in progesterone receptors (PR), but are resistant to estrogens and antiestrogens. Their PR are estrogen-independent, and this permits progestins to be studied in an estrogen-free system. We have used these cells to assess the receptor-binding properties and the biological actions of RU38 486. Since RU38 486 absorbs UV at approximately 300 nm, this wavelength was used to covalently photolink the drug to PR in situ. Like the synthetic progestin R5020, low concentrations (10 nM) of [3H]RU38 486 bind two PR subunits in nuclei of T47Dco; glucocorticoid receptors are not bound. RU38 486 has a high affinity for PR in vitro (Kd approximately 2 nM at 0-4 C), and in intact cells, low concentrations (6-8 nM) transform more than 95% of PR to a high affinity nuclear binding state. In contrast to progesterone, the compound is not metabolized, so that it chronically (3-6 days) suppresses PR replenishment. These biochemical properties of RU38 486 are typical of synthetic progestins, but distinguish it from pure glucocorticoids. To bioassay RU38 486, we have measured growth and insulin receptors, since in T47Dco, physiological concentrations of progestins inhibit proliferation and increase the number of cell surface insulin-binding sites. Like progestins, RU38 486 is growth inhibitory; unlike progestins, it fails to stimulate insulin receptors and partially blocks their stimulation by R5020. Thus, RU38 486 has dual progestin agonist/antagonist actions depending on the biological response measured. PMID- 4039657 TI - Diencephalic sites of progesterone action for inhibiting aggression and facilitating sexual receptivity in estrogen-primed golden hamsters. AB - Diencephalic sites of action of progesterone (P) responsible for inhibiting aggression and facilitating sexual receptivity were examined in ovariectomized golden hamsters primed with Silastic capsules of estradiol. P was applied centrally by inserting a hormone-filled, 27-gauge cannula into a 22-gauge guide cannula that was implanted unilaterally in the medial preoptic area (MPO), the anterior hypothalamus (AH), or the ventromedial hypothalamus (VMH). Control implants consisted of cholesterol-filled cannulae placed within the same regions of the brain. Tests for sexual and aggressive behavior occurred 1, 2, 4, and 6 h after hormone implantation by introducing a sexually experienced male into the home cage of the female. Nine of 20 females with P in the VMH exhibited lordosis in comparison to 1 of 12 females in the MPO group and 5 of 16 animals in the AH group. The induction of sexual responsiveness after P implantation in the VMH was further demonstrated in 6 of 11 ovariectomized-adrenalectomized females, indicating that the observed receptivity was not contingent upon activation of the hypothalamic-pituitary-adrenal axis. In addition to the receptive promoting action of P in the VMH, P implantation in the MPO and VMH but not in AH regions was highly effective in inhibiting female biting attacks upon males. In summary, these findings indicate that P can both facilitate sexual receptivity and inhibit aggressive behavior and that P induces these changes in behavior at different locations in the diencephalon. PMID- 4039658 TI - Local injections of human or rat growth hormone or of purified human somatomedin C stimulate unilateral tibial epiphyseal growth in hypophysectomized rats. AB - The growth-promoting actions of GH are thought to be mediated by somatomedin(s) (Sms), but unilateral bone growth in hypophysectomized (HX) rats given local injections of human (h) GH has been reported. Using slightly different methods, we have confirmed these results with purified hGH and have extended them to show that four daily injections directly into the tibial epiphyseal plate of 1 or 5 micrograms/day purified rat GH or recombinant DNA-derived hGH, but not of hPRL (6 micrograms/day) caused significant cartilage growth compared to that of the vehicle-injected contralateral tibia in rats that had been HX 14 days before the first injection. Thus, it is unlikely that the effects of GH are due to contaminating growth factors in the GH preparations, because the bacteria-derived preparation of hGH, which is unlikely to have such contaminants, was also active. Furthermore, we have shown that similar injections of 100 or 500 ng/day purified hSm-C caused unilateral tibial growth in rats HX 8 days, but not 14 days, before the first injection. These results demonstrate that both GH and Sm-C have direct growth-promoting effects on cartilage in vivo and are compatible with the theory that GH may act by stimulating local SM synthesis. PMID- 4039659 TI - Somatomedin-C stimulates glycogen synthesis in fetal rat hepatocytes. AB - The effects of somatomedin-C/insulin-like growth factor I (Sm-C) on glycogen metabolism in cultured hepatocytes from 20-day-old rat fetuses have been examined and compared with the effects of insulin. Sm-C (25-375 ng/ml; 3.25-50 nM) stimulated dose-dependent increases in [14C]glucose incorporation into glycogen (14.4-72.9%; P less than 0.001) and total cell glycogen content (10.6-34.3%; P less than 0.01). Maximal stimulation of glycogen synthesis by Sm-C occurred at 2 4 h of incubation. Insulin (10 nM to 10 microM) also stimulated [14C]glucose incorporation but its potency was only 1/20th that of Sm-C. The time course of stimulation of glucose incorporation by insulin was identical to that of Sm-C, the dose-response curves of the two hormones were parallel, and the maximal effects of insulin were not enhanced by simultaneous exposure of cells to Sm-C. These findings suggest that Sm-C and insulin stimulate glycogenesis in fetal liver through similar or identical mechanisms. Since the potency of Sm-C was 20 times greater than that of insulin, the glycogenic action of insulin in fetal liver may be mediated through binding to a hepatic receptor which also binds Sm C. In addition to having mitogenic effects on fetal tissues, Sm-C may have direct anabolic effects on fetal carbohydrate metabolism. PMID- 4039660 TI - Uptake, translocation, and transformation of pentachlorophenol in soybean and spinach plants. AB - Soybean plants were grown for 90 days and spinach plants for 64 days in a mixture of sterilized greenhouse soil and sand containing 10 ppm pentachlorophenol. All plant parts and soil samples were extracted and separated into nonpolar and polar fractions. Major nonpolar and polar metabolites were identified by gas-liquid chromatography and mass spectrometry. Nonpolar fractions from both soybean and spinach plants were found to contain pentachlorophenol and its metabolites, 2,3,4,6-tetrachlorophenol, methoxytetrachlorophenol, 2,3,4,6-tetrachloroanisole, and pentachloroanisole. Cleavage of polar metabolites from the soybean plants by acid hydrolysis yielded organic solvent-extractable products. These products were identified as pentachlorophenol, 2,3,4,6-tetrachlorophenol, and methoxytetrachlorophenol. Cleavage of polar materials from spinach plants yielded only pentachlorophenol. The polar metabolites from the soybean plants were also subjected to enzymatic cleavage by beta-glucosidase. The conjugates consisted mostly of O-glucosides of the same metabolites released by acid hydrolysis. Failure of hydrolysis by aryl sulfatase indicated that very little or no sulfates were present. The metabolites found in the plants were not detected in soil samples obtained from pots immediately after the plants were harvested. PMID- 4039661 TI - Anomalous nuclease digestion of Holothuria sperm chromatin containing histone H1 variants. AB - We have investigated the micrococcal nuclease digestion of chromatin from the spermatozoa of the sea cucumber Holothuria tubulosa. This chromatin contains minor protein variants related to histone H1 with a high proportion of basic amino acids. One of these variants, protein phi 0, represents about 4% of the total histones. It is 78 amino acids long and its amino acid composition and sequence are related to the very basic C-terminal region of histone H1. The presence of these proteins induces an unusual digestion pattern. Oligonucleosomal particles which are soluble at 150 mM NaCl are depleted of protein phi 0 and they are also defective in histone H1. A low percentage of the insoluble material can be solubilized at lower NaCl concentrations (50 mM). These oligonucleosomal particles show a very peculiar protein content, since at early digestion times, they contain histone H1 and protein phi 0 exclusively. We conclude that these particles arise from a cooperative displacement of core histones by protein phi 0 and histone H1. These results show that minor changes in histone H1 complement can result in the formation of artifactual particles upon microccocal nuclease digestion. These observations may be of interest in other systems which contain H1 variants. PMID- 4039662 TI - Time-resolved fluorescence of bacteriophage Pf1 DNA-binding protein. Determination of oligonucleotide and polynucleotide binding parameters. AB - The binding of oligonucleotides and polynucleotides to the Pf1 DNA-binding protein was followed by fluorescence spectral shift and lifetime measurements, which gave an anomalous value for the stoichiometry of binding. The anomaly was investigated in detail using fluorescence depolarisation to measure the aggregation during the titration and showed that all the fluorescence parameters are related to the specific aggregation of dimers on ligand binding. At saturation, complexes of the protein with the octanucleotide d(GCGTTGCG) and the hexadecanucleotide (dT)16 have rotational correlation times, phi, of 50 ns and 85 ns, corresponding to protein tetramers and octamers, respectively. In the presence of the tetranucleotide d(CGCA) the protein remains as the native dimer (phi = 19 ns). The titration curves could be analysed in terms of two non equivalent binding sites, with binding constants K1 and K2. Comparison of K1 values for oligonucleotide binding leads to an estimated (single-site) intrinsic binding constant Kint approximately equal to 3 X 10(4) M-1 and a cooperativity parameter omega approximately equal to 100, in agreement with the apparent binding constant Kapp approximately equal to 3 X 10(6) M-1 for polynucleotides. Binding to the second site on the protein dimer is greatly reduced and cannot be determined accurately. The results suggest that the protein dimers bind cooperatively by lateral association along the DNA and that occupation of only one of the two DNA-binding sites of the protein dimers is sufficient to stabilize the nucleoprotein complexes. PMID- 4039663 TI - The role of carboxyl groups in the function of endo-beta-1,4-glucanase from Schizophyllum commune. AB - The endo-beta-1,4-glucanase from Schizophyllum commune was purified to homogeneity by a modified procedure that employed concanavalin A-Sepharose. The catalytic site of the enzyme has previously been proposed to consist of Glu-33 and Asp-50 that act in a manner analogous to lysozyme [Yaguchi, M., Roy, C., Rollin, C.F., Paice, M.G. & Jurasek, L. (1983) Biochem. Biophys. Res. Commun. 116, 408-411]. The role of carboxyl groups in the mechanism of action was delineated through kinetic and chemical modification studies. The rate of endoglucanase-catalysed hydrolysis of CM-cellulose was determined viscometrically at 30 degrees C, 0.06 M ionic strength and pH 2.5-9.0. The pH profile for maximum velocity gave the kinetic apparent pK values 3.8 and 6.6 and for initial velocity the pK values 3.7 and 6.1. Treatment of the endoglucanase with diethylpyrocarbonate resulted in the modification of all the four histidyl residues present in the enzyme with the retention of 95% of the original enzymatic activity. A water-soluble carbodiimide completely inactivated the cellulase and kinetic analysis indicated that at least one molecule of carbodiimide binds to the enzyme for inactivation. The pH dependence of the inactivation is consistent with the modification of carboxyl groups. The binding of an inhibitor, cellobiose, prior to carbodiimide modification protected the enzyme from rapid inactivation. Titration of the enzyme with dithiobis(2 nitrobenzoic acid) indicated the absence of free thiol groups. Reaction of the endoglucanase with tetranitromethane resulted in the modification of six of the fourteen tyrosyl residues of the enzyme with approximately 35% diminution in activity. PMID- 4039664 TI - Coupling of cytoskeleton functions for fibroblast locomotion. AB - Using a chick cell phenotype specialised for locomotion with morphometric measurements made possible by modern instrumentation technology, we have reinvestigated motile functions in fibroblast locomotion. Quantitative analysis of rapid fluctuations in cell form and organelle distribution during locomotion showed many significant correlations between different parts of the cell despite much irregularity in individual displacements over the time scale of the order of one second. These broke down when external perturbations caused changes in shape or direction. Partial energy deprivation caused the cells to lose control of shape and organelle distribution even though forward protrusion continued unaffected. Cytoplasmic displacements shown by marker mitochondria correlated with adjacent fluctuations at the leading edge, and drug treatments which increased the amplitude of mitochondrial movements caused visible protrusions in projected positions at the leading edge. We conclude that fibroblast locomotion may be driven coordinately by a common set of motility mechanisms and that this coordination may be lost as a result of physical or pharmacological disturbance. Taking our evidence with results from other Laboratories, we propose the following cytoskeleton functions. (i) Protrusive activity, probably based on solation--gelation cycles of the actin based cytoskeleton and membrane recycling which provides cellular and membrane components for streaming through the cell body to the leading edge; this is Ca++ sensitive but relatively energy insensitive. (ii) Constraining activity on the cell membrane and on certain organelles to maintain shape and so facilitate directionality and the drawing along of the trailing body; this is Ca++ insensitive but relatively energy sensitive. (iii) Channeling function of microtubules to direct the flow towards multiple foci on the leading edge, and so determine cell polarity. Such a mechanism of locomotion for fibroblasts has many features consistent with evidence for other cell types, especially amoebae and leukocytes. PMID- 4039665 TI - Influence of the polyamine spermine on the organization of cortical filaments in isolated cortices of Xenopus laevis eggs. AB - Microinjection of spermine into Xenopus laevis eggs induces precocious furrowing, and together with known spermine-actin interactions, suggests that spermine may be affecting cortical microfilaments involved in cytokinesis. An electron microscopic study of injected eggs revealed that the ultrastructure of the induced furrows was similar to that of both artificially activated eggs and fertilized eggs. In isolated egg cortices, increasing spermine concentrations (1, 3 and 10 mM) resulted in marked changes in cortical microfilament organization. At low concentrations, spermine appeared to stabilize microfilaments and at higher concentrations induced lateral associations between filaments and formation of bundles. The actin nature of these cortical microfilaments was confirmed by immunocytochemistry. The electrophoretic profiles of proteins from control and spermine-treated isolated cortices were similar. Although the total protein content of isolates in 3 and 10 mM spermine was elevated, the relative actin content remained constant. The results are in agreement with previous in vitro studies of polyamine interactions with actin and support the hypothesis that a polyamine-actin interaction may be important in the regulation of cytokinesis. PMID- 4039666 TI - An examination of the soluble oligomeric complexes extracted from the red cell membrane and their relation to the membrane cytoskeleton. AB - A part of the spectrin extracted from red cell membranes at low ionic strength occurs in the form of a high-molecular weight oligomeric complex with actin and proteins 4.1 and 4.9. When the extraction is performed at 35 degrees, the spectrin is present in this complex as the dimer, all higher forms being dissociated. We have been unable to establish any correlation between the fraction of the spectrin thus complexed and the metabolic state of the cell. At least a large part of the complex appears to be a defined monodisperse species, sedimenting at 31S. The actin is present as short protofilaments. The average number of spectrin molecules associated with each molecule of complex has been studied by cytochalasin binding and electron microscopy. The complexes present the appearance in the electron microscope of spiders, in which the legs are spectrin dimers, attached to a globular element, containing by inference, actin and proteins 4.1 and 4.9; they are active in nucleating the polymerization of G actin. The complexes are extremely stable, being resistant to dissociation under the conditions of the deoxyribonuclease assay, even after treatment with trypsin to degrade the actin-associated proteins. It is suggested that the complexes represent intact junctions of the membrane cytoskeletal network. Relevant structural features of the network are revealed by electron microscopy. The results lead to inferences concerning the mechanism of dissociation of the network from the membrane. PMID- 4039667 TI - Scintigraphic visualisation of Walker carcinoma-256 in Sprague-Dawley rats by means of 99mTc-labelled monocytes. AB - Labelled macrophages accumulate in Walker carcinosarcoma-256 after 'in vivo' and 'in vitro' stimulation with a lectin and are therefore theoretically suitable for scintigraphic tumour detection. At present, routine application of the technique in man is precluded by: the use of PHA, and a labelling method for macrophages with considerable limitations to its application and which results in significant uptake of activity in liver and spleen. However, the purpose of the study was primarily to demonstrate the principle of a possible alternative to the use of labelled monoclonal antibodies for the scintigraphic detection of tumours. PMID- 4039668 TI - Pharmacological interventions and myocardial infarct size in rat. AB - Infarction was produced in male albino rats by left coronary artery ligation and infarct size was measured using NBT staining. Imidazole significantly decreased the myocardial infarct. The effect did not appear to be mediated through the thromboxane synthetase inhibitory property of imidazole because dazoxiben (a selective thromboxane synthetase inhibitor) failed to produce a similar effect. Propranolol pretreatment decreased the infarct size but treatment after coronary ligation increased it. Reserpine treatment did not alter the infarct size significantly. PMID- 4039669 TI - Opposite effects of sulpiride and metoclopramide on amphetamine-induced stereotypy. AB - The effects of the atypical neuroleptic sulpiride (0-20 mg/kg s.c.) and the classical neuroleptic metoclopramide (0-4 mg/kg s.c.) on behaviours produced by D amphetamine (0-5 mg/kg i.p.) were measured in a time-sampling observational paradigm in rats. Sulpiride had one clear dose-dependent effect: it enhanced amphetamine-induced stereotyped behaviours (repetitive head movements, sniffing down and some gnawing). In contrast, metoclopramide dose-dependently decreased amphetamine-induced stereotypy, locomotion, rearing, and sniffing up, and concurrently antagonized the suppression of lying down produced by amphetamine. Sulpiride's facilitatory effects on amphetamine-induced stereotypy follow a pattern previously observed for two other atypical neuroleptics: clozapine and thioridazine. This may be a common effect of atypical neuroleptics. Since these neuroleptics are antipsychotic, amphetamine-induced stereotypy appears to be a poor animal model for human psychoses. It is suggested that sulpiride's effects may be mediated through a preferential presynaptic versus postsynaptic action on dopamine neurons in the nigrostriatal bundle. PMID- 4039670 TI - Recovery of the muscarinic cholinergic receptor from its down-regulation in cultured smooth muscle. AB - The recovery of the muscarinic cholinergic receptor (mAChR) from its down regulation by long-term exposure to ACh was investigated. This was done to obtain information about regulation of the mAChR. Exposure of guinea-pig vas deferens to 30 microM ACh for 24 h decreased the amount of mAChR to 30% of the initial level, as measured with L-[3H]quinuclidinyl benzilate (QNB). The amount of mAChR was restored to 190% of its prewithdrawal level within 48 h of removal of ACh, without change in the KD value for L-[3H]QNB. This restoration was entirely dependent on protein synthesis. The half-life of the receptor was calculated to be 69 h. The recovery of mAChR was blocked by treatment with antimicrotubular agents, carboxylic ionophores, or 5 mM EGTA, which affect membrane protein synthesis. However, cytochalasin B and cyclic nucleotide derivatives had no effect. These data indicate that the recovery of mAChR was due to new synthesis of mAChR. The findings suggested that microtubules and the Golgi apparatus were involved in the biosynthesis of mAChR and that extracellular Ca2+ was necessary for the synthesis. Unlike the case with nicotinic AChR, the synthesis did not seem to be increased by cAMP or high extracellular Ca2+. PMID- 4039671 TI - Barbed end-capping protein regulates polarity of actin filaments from the human erythrocyte membrane. AB - The directional polymerization of G actin on single-layered erythrocyte membranes has been examined in the presence or absence of a barbed end-capping protein isolated from sea urchin eggs. When in the absence of the capping protein the single-layered erythrocyte membranes were incubated with 2 microM of G actin, exceeding the critical concentrations, about half of polymerized actin filaments became orientated with arrowheads of heavy meromyosin pointing toward the membrane at 2 microM of G actin. In contrast, in the presence of the capping protein, nearly 90% of the polymerized filaments were directed with arrowheads of HMM pointing away from the membranes. Furthermore, only preincubation of the erythrocyte membranes with the capping protein is effective to a similar extent in regulating the polarity of actin filaments from the membranes. The results obtained are discussed particular as regards to the physiological roles of the barbed end-capping protein in situ. PMID- 4039672 TI - The effect of age on the control of water conservation in the laboratory mouse- metabolic studies. AB - Age-related changes in the intake of food and water, and the output of faeces and urine were investigated in C57BL/Icrfat mice of 6 and 24 months of age. Animals were singly housed in a metabolic cage for a period of 30 days. 14 days were allowed for acclimatization before the animals were dehydrated for 24 hours. 10 days of rehydration were allowed prior to a hyperosmotic challenge with 3% sodium chloride in the drinking water. The animals were then observed for 5 more days of rehydration. Urine was collected and analysed with regard to sodium, potassium, urea and vasopressin output/24 hours (/100g body weight), and the osmotic pressure of the urine was determined. Data were analysed by a 2 factor analysis of variance with repeated measures on one factor. Significant changes were detected in the control of body weight, potassium, sodium and urea outputs. No age-differences were detected in the intake of food or water, the output of faeces or urine, the urine osmotic pressure or the excretion of vasopressin. However, significant changes in these variables were detected in both age groups on the days of physiological challenge. The conclusion drawn is that in the mouse strain studied, and for the period of the lifespan investigated, there is no age related defect in the secretion of vasopressin. However, there are trends in the data suggesting a decreased responsiveness of the kidney with age. PMID- 4039673 TI - Effect of rabbit antimouse brain serum on marrow cells capable of curing W/Wv mice. AB - The W/Wv mouse has a recessively inherited defect in hematopoietic stem cells (HSC) but can be cured of its hematopoietic abnormalities by infusion of marrow from a co-isogeneic, +/+ mouse. The "curative" cell for the W/Wv is thought to be a subcompartment of the HSC that is capable of forming hematopoietic spleen colonies (CFU-S) in irradiated mice. The curative HSC must have a very high proliferative potential and it is known that HSC with variable degrees of proliferative potential are found within the CFU-S compartment. Rabbit antimouse brain serum (RAMBS) was used to treat +/+ marrow and its effect upon CFU-S and upon curative cells was compared with the effect of normal rabbit serum (NRS) or of sham treatment. CFU-S were reduced to 70%-79% of control by NRS and to 8%-9% by RAMBS. Curative cells for the W/Wv were not detectably reduced by NRS; they were reduced by RAMBS, but to only approximately 20%-30% of control. Thus, it appeared to a certain degree that RAMBS spared HSC with a high proliferative potential when compared with its effect on the entire CFU-S compartment. PMID- 4039674 TI - Effects of chronic ethanol consumption on pyramidal neurons of the mouse dorsal and ventral hippocampus: a quantitative histological analysis. AB - The effects of a 9-month period of ethanol consumption (followed by 3 or 6 months of withdrawal) on the hippocampus of mice were investigated. Compared with control animals, a loss of hippocampal neurons was observed on histological sections from ethanol-treated mice. This loss was greater in the ventral hippocampus (-18.6% to -18.7%) than in the dorsal hippocampus (-5.2% to -8.5%). However, the nucleus diameter, as well as the number of dendritic spines (studied using the Golgi-rapid impregnation) of the remaining neurons was not significantly affected by chronic ethanol consumption in our experimental conditions. PMID- 4039675 TI - Qualitative and quantitative changes of mouse cerebellar synapses after chronic alcohol consumption and withdrawal. AB - For 4 months C57 mice were fed a nutritionally complete diet containing 9% alcohol or isocaloric sucrose and killed then or after 4 months recovery on standard food pellets. Electron microscopy was used to count synapses among the cerebellar Purkinje cell dendrites and a significant 13% reduction was found in the alcohol recovery group. The shape of the postsynaptic density material was studied and a significant 11% increase in length found in the alcohol group. The smaller thickness of the postsynaptic material in animals of the alcohol recovery group may be representative of new synaptic formation. PMID- 4039676 TI - The extent of the necrotic lesion in the apical end of the rat incisor pulp seen after Adriamycin administration. AB - The extent of the necrotic lesion produced by adriamycin in the apical end of the rat incisor was investigated. Male Sprague Dawley rats were injected intravenously with adriamycin (5 mg/kg body weight), and sacrificed by perfusion with a 2.5% buffered glutaraldehyde solution 1 d after injection. Controls injected with only physiological saline were treated in the same manner. One micron thick plastic serial sections were prepared from the apical end of the incisor, and a schematic representation of the entire lesion as seen in longitudinal section was reproduced from each fiftieth section. Cell destruction was observed for 2.2 mm within the pulp. The lesion extended further incisally in the lingual portion than in the labial portion. The bulbous portion of the odontogenic organ was not affected. This study indicates that the cytotoxicity of adriamycin appears to affect mainly proliferating immature precursor cells within the mesenchyma, and the preodontoblasts. PMID- 4039677 TI - Regeneration of axonal endings of neuromuscular junctions of the soleus muscle in rats under conditions of hypodynamia. AB - The purpose of the experiments performed was morphometric ultrastructural evaluation of the regeneration of axonal endings after sectioning of nerves in rats kept under conditions of hypodynamia. The investigation indicated a retardation of regeneration of the axonal endings of neuromuscular junctions after denervation of the soleus muscle in rats kept under conditions of hypodynamia as compared with those of the control group. The retarded regeneration of the axonal endings of neuromuscular junctions in experimental animals as compared with that in the control group may be referred to the above mentioned enzymatic and electrolytic disturbances caused by restriction of mobility. PMID- 4039678 TI - Study of spontaneous rosette formation and changes of sialic acid content in the surface glycoproteins of macrophages induced by hamster transplantable melanomas. AB - The influence of two kinds of transplantable melanomas on the content of sialic acids in the surface glycoproteins of hamster peritoneal macrophages was studied, and the ability of these cells to form spontaneous rosettes. It has been found that the intensification of rosette formation by macrophages with SRBC depends on the melanoma line. No correlation has, however, been found between changes in the sialic acids content and the ability of macrophages to form rosettes under the influence of melanomas differing in malignancy. PMID- 4039679 TI - Influence of age on the carotid bodies of spontaneously hypertensive (SHR) and normotensive rats. II. Alterations of the vascular wall. AB - The carotid bodies of spontaneously hypertensive rats (SHR) of the Okamoto-Aoki strain and of age-matched normotensive Wistar rats (NWR) were studied with respect to their size and the histological appearance of their arterial vessels. The animals were aged 3-6 d, and 5-6, 15-20, 30-40 and 50-70 weeks. The development of hypertension in the SHR started at an age of 5-6 weeks and was fully established at 15-20 weeks (mean systemic arterial blood pressure at about 160 mm Hg). When compared with the age-matched normotensive control rats (NWR) the SHR in the established phase of hypertension showed enlarged carotid bodies, an increase of the thickness of the media of the carotid body artery and circumscript pad-like thickening of the vascular wall within the carotid bodies. Repeatedly in particular in the old SHR, also a hyalinosis of the small branches of the glomic artery was found. These pathological changes regularly narrowed the lumen of the vessels seized; sometimes to a considerable extent. Such vascular alterations were never found in the newborn (3-6 d old) SHR and were also not demonstrable in the NWR. Thus these vascular alterations in the carotid body vessels of the adult SHR are supposed to be the result of the high systemic arterial blood pressure. The data indicate that long-lasting high systemic arterial blood pressure leads to changes of the wall of the arterial vessels of the carotid and presumably also the aortic bodies thus inducing an ischemic hypoxia of the specific chemoreceptive tissue and a chronic stimulation of the arterial chemoreceptors. PMID- 4039680 TI - Ultrastructural morphometry of cultivated smooth muscle cells from normotensive and hypertensive rats. AB - Cultivated aortic smooth muscle cells (SMC) derived from normotensive and hypertensive rats were analyzed by transmission electron microscopy and ultrastructural morphometry. SMC cultures obtained from hypertensive rats showed an increase in cell size and a higher percentage of large, often polynuclear cells. The stereological data of mitochondria, rough endoplasmic reticulum (RER) and secondary lysosomes were determined by measuring area according to the "Delesse principle". The organelle contents of small and large cells of each group were only slightly different. Significant changes were found between SMC from normotensive and hypertensive rats: The volume density Vv of mitochondria per unit cytoplasm volume was increased up to 48% in small and 50% in large SMC from hypertensive rats compared to those of control animals. The numerical density Nv of secondary lysosomes per unit cytoplasm volume was increased up to 68% in small and 267% in large SMC from hypertensive rats. The content of rough endoplasmic reticulum varied tremendously between the individual cells. All these stereological data represent relative parameters of cell organelles relative to the unit cytoplasm volume. Therefore the differences between the absolute values would be even higher since SMC from hypertensive rats are shown to have a higher mean cell size and volume. We conclude that the effect of experimental hypertension, resulting in an activation of SMC, persists even when the cells are transferred to in vitro conditions. PMID- 4039681 TI - Wound-induced alterations in survival of 60Co irradiated mice: importance of wound timing. AB - Wounding mice shortly before or shortly after lethal 60Co irradiation enhances survival. Survival of wounded-irradiated mice may be due to enhanced hematopoietic recovery as measured by endogenous spleen colony (E-CFU-s) formation. PMID- 4039682 TI - Intergeneric interactions between Eimeria separata (Apicomplexa) and Nippostrongylus brasiliensis (Nematoda) in the rat. AB - Ova production in Nippostrongylus brasiliensis infected rats was significantly greater than in rats singly infected with the helminth when Eimeria separata infections were introduced 4, 6 and 11 days postinoculation with N. brasiliensis. Patent periods were unaltered during concurrent infections. These results suggest that the presence of E. separata affects helminth fecundity but does not increase N. brasiliensis longevity as has been shown with E. nieschulzi. PMID- 4039683 TI - Dephosphorylation suppresses the activity of neurofilament to promote tubulin polymerization. AB - The phosphate content of neurofilament was diminished by half, from 49.4 to 22.9 nmol/mg, by treatment with alkaline phosphatase. Dephosphorylation decreased the activity of neurofilament to promote tubulin assembly. This suppression was supposed to be mainly due to dephosphorylation of the 200 kDa subunit of neurofilament. Dephosphorylation of the isolated 200 kDa subunit caused suppression of its activity to promote tubulin polymerization. These results suggest that changes in the phosphate content modulate interaction of neurofilament with tubulin. PMID- 4039684 TI - Purification of antineoplastic factor from eggs of a sea hare. AB - An antineoplastic factor inducing tumor lysis was purified to apparent homogeneity from the supernatant of a homogenate of eggs of the sea hare Aplysia kurodai. On gel filtration, the purified substance gave a single band of material of 250 kDa containing 3 different subunits and this band coincided with cytolytic activity. The purified factor was half-maximally active at 10-60 ng protein/ml and lysed all tumor cells tested, but not normal cells. PMID- 4039685 TI - [Dynamics of the induction of experimental neuroses caused by chronic emotional stress]. PMID- 4039686 TI - [Changes in blood monoamine and 11-hydroxycorticosteroid levels in rats under the action of stress]. PMID- 4039688 TI - [Infraslow activity and temperature of the brain during tests with emotional tension]. AB - Infraslow electrical activity and brain temperature were recorded with implanted electrodes and differential thermocouples in rabbits. Stimulation of gyrus cinguli increased the amplitude of infraslow activity and reduced its frequency. Stimulation of the hypothalamus entailed both changes of the infraslow activity and raise of the brain temperature. The effects of stimulation were altered after administration of antihypoxants. PMID- 4039687 TI - [Biotransformation of prostaglandin E1, bradykinin and angiotensin I in pulmonary circulation in rats with spontaneous hypertension]. PMID- 4039689 TI - Ontogenic development of proliferative and polyclonal antibody and autoantibody responses to staphylococcal peptidoglycan, protein A and cell walls in mice. AB - In the spleens of newborn mice, polyclonal IgM, IgG and IgA responses were low to protein A, cell walls (CW) and PWM, intermediate to peptidoglycan (PG), and high to LPS. Small, not significant increases in Ig responses to LPS (which occurred during the first 2 wks) were observed, whereas, the responses to PG, protein A, CW and PWM continued to increase for 8 wks, and the increases were high and significant. In most cases, there was no change in the dose response and kinetics patterns (characteristic for each stimulant) during ontogeny. Ontogenic development of autoantibody-secreting cells was different from the development of cells secreting all Ig and anti-SRBC antibodies. The increases in the numbers of cells secreting IgM anti-DNA and IgM anti-bromelin-treated mouse RBC antibodies in response to LPS and PG during postnatal development were larger than the increases of all IgM-secreting cells. In contrast, the increases of IgM anti-DNA secreting cells in response to protein A and PWM were smaller than the increases of all IgM-secreting cells. The frequencies of cells secreting anti-DNA antibodies in LPS- and PG-stimulated cultures were low in newborns and continued to increase until 8 wks of age, but they were high and did not change throughout ontogeny in protein A-stimulated cultures. Changes in the frequencies of anti-RBC antibody-secreting cells were less distinct and mostly insignificant. Postnatal changes in mitogenic responses were smaller and not correlated with the development of polyclonal Ig responses. Our data indicate different modes of ontogenic development of the ability of cells to produce polyclonal Ig, autoantibodies and heteroantibodies, and to synthesize DNA, in response to different stimulants. PMID- 4039690 TI - Spatial changes in poly(A) concentrations during early embryogenesis in Xenopus laevis: analysis by in situ hybridization. AB - The dorsal-ventral axis of the Xenopus embryo is approximately determined by the point of sperm entry, which occurs randomly about the animal-vegetal axis of the egg. Two cytoplasmic components were studied whose spatial arrangements and local concentration patterns appear to reflect the forming dorsal-ventral axis. First, three-dimensional maps depicting the rearrangements of different size classes of yolk platelets were reconstructed from serial sections. These maps provide information on the time when movements occur and the intracellular directions and distances components can travel within the early embryo. Second, local poly(A) concentrations were observed using a [3H]poly(U) in situ hybridization probe. Poly(A) concentrations were observed to change reproducibly from fertilization to late cleavage. Two cytoplasmic areas were found to undergo major, stage-specific increases in poly(A) concentration. PMID- 4039691 TI - Analysis of sea urchin egg cortical transformation in the absence of cortical granule exocytosis. AB - A burst of endocytosis accompanying microvillar elongation follows cortical granule exocytosis in normal sea urchin development. By 5 min postfertilization the burst is over and a lower level of endocytosis ensues (constitutive phase). To determine whether microvillar elongation and initiation of endocytosis are necessary concommitants of cortical granule exocytosis we utilized Chase's (1967, Ph.D. thesis, University of Washington, Seattle) high-hydrostatic pressure technique to block the latter and then examined developing eggs for endocytosis and microvillar elongation. To accomplish this, eggs were fertilized, after which hydrostatic pressure was quickly raised to 6000-7000 psi at the start of cortical granule exocytosis and maintained for 5 min. Only the cortical granules immediately surrounding the sperm penetration site were secreted (about 3% or less of the egg's total number of cortical granules). Blockage of major cortical granule exocytosis had the following consequences on surface events during first division: (1) The endocytosis burst normally associated with cortical granule exocytosis was effectively eliminated as was early microvillar elongation and elevation. Both occurred to a limited extent around the sperm penetration site which resulted in a highly localized surface transformation. (2) By 20 min after fertilization endocytosis began over the rest of the egg surface in the absence of any further cortical granule exocytosis. (3) Subsequently, during a 30-min period starting midway between fertilization and first cleavage microvilli more than doubled in length and endocytosis levels increased severalfold. These events brought about a complete surface transformation similar to that which normally occurs in early development but in the absence of cortical granule exocytosis. By first cleavage surfaces and cortices of high-pressure-treated and control eggs were nearly indistinguishable except for the presence of cortical granules in cortices of the former. Pressure-treated eggs cleaved normally and developed to larval forms overnight. The period of late surface transformation in high pressure-treated Strongylocentrotus purpuratus eggs corresponds in timing and some of its characteristics to second phase microvillar elongation observed in normal development in this species and also in S. droebachiensis development. These observations suggest, therefore, that microvillar elongation and endocytosis are necessary membrane remodelling events which must occur for normal development even in the absence of membrane addition from the cortical granules. PMID- 4039692 TI - Effect of 1-desoxynojirimycin derivatives on small intestinal disaccharidase activities and on active transport in vitro. AB - The influence of two new 1-desoxynojirimycin derivatives, BAY m 1099 and BAY o 1248, on rat small intestinal disaccharidases (sucrase, maltase, isomaltase, glucoamylase, lactase, trehalase) and alkaline phosphatase activity has been investigated in vitro. Both compounds are very potent alpha-glucosidase inhibitors. Tested in the range of 0.1-5.0 micrograms/ml, inhibition is strongest on sucrase (up to 97.1%) and glucoamylase (up to 96.7%). BAY m 1099 also reduced (up to 56.4%) beta-galactosidase (lactase) activity. For both inhibitors a competitive type of sucrase inhibition was demonstrated (Lineweaver-Burk plot). Affinity versus sucrase was unusually tight. The Ki of BAY m 1099 versus sucrase amounted to 1.14 x 10(-7) M and of BAY o 1248 to 6.92 X 10(-8) M (Dixon plot). Both inhibitors did not impair active transport of L-leucine or methyl-alpha-D glucoside into everted rings of rat jejunum in vitro. PMID- 4039693 TI - Effect of deoxycholic acid on the tumour incidence, distribution, and receptor status of colorectal cancer in the rat model. AB - It has previously been observed that 25% of human colorectal cancers contain specific receptors to deoxycholic acid (DCA). In the present study, the effect of intrarectal instillation of DCA on tumour number, distribution, size, and DCA receptor status was measured in rats receiving the colorectal carcinogen, azoxymethane. Rats treated with azoxymethane and intrarectal DCA developed significantly more colorectal cancers than rats receiving azoxymethane and intrarectal saline (median 11.5, range 8-17 vs. median 6.0, range 3-9 tumours/rat, respectively, p less than 0.01). This reflected a significantly higher number of tumours in the distal colon of the DCA-treated group (median 8.0, range 5-10 tumours/rat) compared to the saline-treated group (p less than 0.01). In those rats receiving DCA and azoxymethane, 5 of 12 tumours tested were found to be DCA receptor-positive, compared with only 1 of 11 in the saline and azoxymethane group. These results confirm the belief that DCA acts as a tumour promoter, and suggest a possible role for DCA receptors. PMID- 4039694 TI - Oral form of acyclovir approved. PMID- 4039695 TI - Chronic ethanol consumption alters rat liver plasma membranes and potentiates release of alkaline phosphatase. AB - The aim of this study was to investigate possible mechanisms involved in the elevation of serum alkaline phosphatase activity in alcoholics. Male Sprague Dawley rats were pair-fed nutritionally adequate liquid diets containing ethanol as 36% of energy or an isocaloric amount of carbohydrate for 4-5 wk. Serum alkaline phosphatase activity was increased moderately but significantly. Hepatocytes isolated from ethanol-fed animals exhibited pronounced morphologic alterations of their plasma membranes by scanning electron microscopy and a reduced content of alkaline phosphatase despite an increase in total liver alkaline phosphatase content. Chronic ethanol feeding also potentiated the release of alkaline phosphatase from the cells during incubation with 50 mM ethanol. Furthermore, chronic ethanol feeding resulted in reduced recovery of alkaline phosphatase in hepatic plasma membranes isolated by sucrose gradient centrifugation but did not affect the recoveries of other plasma membrane markers (5'-nucleotidase and Na+,K+-adenosine triphosphatase) nor the subcellular distribution of alkaline phosphatase in the nuclear, mitochondrial, microsomal, and cytosolic fractions. These findings suggest that the increased serum alkaline phosphatase levels observed in response to chronic ethanol feeding may be due, at least in part, to increased lability of this plasma membrane enzyme. PMID- 4039696 TI - Milk- and soy protein-induced enterocolitis: evidence for lymphocyte sensitization to specific food proteins. AB - Stimulation ( [3H]thymidine incorporation) of blood lymphocytes cultured with food proteins was evaluated in infants with food protein-induced enterocolitis and correlated with the results of oral diagnostic challenges with the same foods (soy, cow's milk, and egg white). The geometric mean stimulation index for lymphocytes from patients with positive oral soy protein challenge that were cultured with soy protein was 8.5, and for patients with positive cow's milk challenge the stimulation index was 6.0 when casein was used in the cultures. Both values are significantly different from the values obtained from patients with negative oral challenges (p less than 0.01). The enhanced lymphocyte responses were specific for the food proteins responsible for clinical symptoms. It is not clear whether these lymphocyte responses are due to systemic immunization secondary to macromolecular absorption, or to an abnormality in immune regulation such as a delay in the development of oral tolerance mechanisms. They suggest, however, that circulating lymphocytes sensitive to the food antigens that produce the clinical symptoms are frequent in infants with this discrete form of food protein hypersensitivity. PMID- 4039697 TI - Parental influences on X chromosome expression. PMID- 4039698 TI - [Importance of the localization of the photocoagulation focus in the therapy of proliferative diabetic retinopathy]. PMID- 4039699 TI - [Bronchial cancer: possibilities and limits of chemotherapy. 2: Non-small cell bronchial cancer]. PMID- 4039700 TI - [Hypertrophic obstructive cardiomyopathy with extensive myocardial fibrosis: case report with autopsy]. AB - An autopsy case of hypertrophic obstructive cardiomyopathy with extensive myocardial fibrosis is reported in a 43-year-old male. His mother died suddenly at 55. At the age of 39 the patient felt fatigue and feverish sensation followed by dyspnea and palpitation on exertion. He responded to beta-blocker and was discharged on the 51st hospital day. He died suddenly during his work three years and one month after discharge. The heart weighs 700 g. The thickness of the ventricular septum measures up to 3.2 cm, and that of the left ventricular posterior wall 2.2 cm. Subaortic endocardium is moderately thickened. Many patchy fibroses of various sizes and broad linear fibroses are mainly observed in the ventricular septum and in the left ventricular free wall. Microscopic examination shows severe fascicular disarray of hypertrophied myocardial fibers in the ventricular septum and in a part of the left ventricular anterior wall. Pericardial fibrosis, granulation tissue with many capillaries, and slight lymphocytic infiltrate are also noted. These findings suggest that the patient have both congenital hypertrophic cardiomyopathy and myocarditis. There are following possibilities as regards the relation between the two: first, haphazard association of cardiomyopathy with myocarditis; secondly, myocarditis triggered the onset or progression, or both, of cardiomyopathy. He also had liver cirrhosis, probably alcoholic, which appears to accelerate the progression of myocardial disarray and fibrosis. PMID- 4039701 TI - Histogenesis of post-mastectomy angiosarcoma--an ultrastructural study. AB - An example of post-mastectomy angiosarcoma was studied by electron microscopy to determine its histogenesis. Unequivocal evidence of endothelial differentiation was found in well and poorly differentiated areas. Positive staining for factor VIII related antigen and negative staining for epithelial membrane antigen further confirmed that the tumour was a true angiosarcoma rather than a peculiar form of carcinomatous metastasis. PMID- 4039702 TI - Under PPS, stringent controls needed in operating room. PMID- 4039703 TI - A new hereditary single band variant of the Gc system. AB - A new single band variant (Gc Ar) or the Gc subtypes not identical with the known Gc variants has been detected in the plasma of a healthy blood donor by isoelectric focusing. Using this technique the variant is represented by a single band which has a similar isoelectric point to the Gc 1C2 anodal band. It is well known that the single band Gc phenotypes remain unaltered after neuraminidase treatment. Nevertheless, the new single band variant (Gc Ar) is altered after neuraminidase treatment as is Gc 2A3. After neuraminidase treatment, the Gc Ar band is affected and moved to the nearby position of the Gc 2 band. Investigation of the proband's family shows that the variant occurs combined with the common alleles Gc 1F, Gc 1S and that it has an autosomal dominant inheritance. PMID- 4039704 TI - Effect of prostaglandins on immune complex interaction with glomerular cells in vitro. AB - Previous studies demonstrated that prostaglandins of the E1 (PGE1) series reduced immune complex (IC) accumulation and inflammation in murine glomeruli in IC glomerulonephritis (GN). This study examines the effect of PGE1 on IC interaction with cultured rabbit glomerular cells and heparan sulfate synthesis by the cells. IC were formed with antigen chemically modified to produce a cationic (CAT) charge or left unmodified (UM). CAT IC binding to cells was greater than UM IC in the absence of PGE1. CAT IC binding to cells was increased by PGE1 while UM IC interaction was not affected. Prolonged exposure of cells to PGE1 enhanced CAT IC binding. Heparan sulfate synthesis by the cells was not affected by the concentrations of PGE1 employed. The findings suggest the benefit provided by PGE1 in murine IC GN may not be due to a direct effect on glomerular cells which reduces glomerular IC accumulation. PMID- 4039705 TI - Inhibition of serum bactericidal reaction by lipopolysaccharide. AB - An Rc-mutant of Escherichia coli that lacks UDPgalactose 4-epimerase grows normally without galactose but makes lipopolysaccharide lacking most of its carbohydrate. Exogenous galactose overrides the mutation and results in the formation of a complete lipopolysaccharide, thereby producing a smooth phenocopy. The smooth phenocopy was much more resistant to the bactericidal activity of normal human serum than was the rough phenotype. More complement was utilized by the rough mutant in the bactericidal process than by the smooth phenocopy. An antiserum was prepared in rabbits to a specific outer membrane protein in the mutant bacterium, the lambda receptor, whose expression could be suppressed by the addition of 10 mM maltose. The effect of the O-antigen in the lipopolysaccharide produced by the smooth phenocopy on the binding of antibody to the lambda receptor was determined. The smooth phenocopy exhibited significantly less binding of antibody than did the rough phenocopy. In addition, expression of the lambda receptor had little effect on the binding of antibody to the lambda receptor in the smooth phenocopy but caused significantly increased binding in the rough mutant. The results suggest that the increased resistance to the lethal action of normal human serum shown by the smooth phenocopy may be due to the blocking of antibody binding sites by the O-antigen of lipopolysaccharide, thereby preventing activation of the classical pathway of complement. PMID- 4039706 TI - Cardiovascular implications of strenuous exercise. PMID- 4039707 TI - Hepatic microsomal alterations during Dipetalonema viteae infection in Mastomys natalensis. PMID- 4039708 TI - Adoptive transfer of immunity to Trichinella spiralis in mice: generation of effective cells by different life cycle stages. PMID- 4039709 TI - Gametogenesis in Plasmodium; the inhibitory effects of anticytoskeletal agents. PMID- 4039710 TI - [Dietary methionine supplementation in the pregnant rat. 1. Food intake of the dam and body weight of the newborn offspring]. AB - A decrease from 18 to 9% of the dietary casein level induces lower food intake in the gestating female rat and weight loss in the newborn rat. Addition of methionine to the diet containing 9% casein improves food intake in the last period of pregnancy. Body weight of the newborn rat is also increased and becomes identical to that of rats born from mothers fed 18% dietary casein. PMID- 4039712 TI - Immunocytochemical localization of interphotoreceptor retinoid-binding protein in developing normal and RCS rat retinas. AB - Interphotoreceptor retinoid-binding protein (IRBP) was localized immunocytochemically in developing normal and RCS rat retinas. IRBP was present in normal and RCS neural retinas on the day after birth (postnatal day 2, P2) to P8 in the space between the neuroblastic layer and the retinal pigment epithelium (RPE). The presence of IRBP prior to the development of outer segments (OS) suggests that OS formation is not linked temporally with IRBP secretion. On P10, staining was confined to the interphotoreceptor space with an intense band of label adjacent to the RPE. This staining pattern persisted in normal rats throughout development and until P18 in RCS rats. On P18, anti-IRBP staining in the RCS was spread evenly throughout the OS layer with no intense band of label adjacent to the RPE and after P18, there was decreased staining with anti-IRBP. On P45 and later, no staining of the RCS retina was found with anti-IRBP. Immunoblots of normal and RCS retinas corroborated the results from immunocytochemical staining. These findings suggest that IRBP may be synthesized in the photoreceptors, but is not abnormal in amount or distribution prior to onset of retinal degeneration in the RCS rat. PMID- 4039711 TI - Vitamin A and interstitial retinol-binding protein in an eye with recessive retinitis pigmentosa. AB - The composition and amount of vitamin A stored in the retinal pigment epithelium and choroid (RPE-Ch) was evaluated in postmortem donor eyes from a patient with retinitis pigmentosa that was probably inherited by an autosomal recessive mode. Additionally, the soluble proteins in the neural retina and RPE-Ch cytosols and interphotoreceptor matrix were examined collectively for the presence of interstitial retinol-binding protein (IRBP). Although there was depletion of the amount of vitamin A stored in the RPE, this was commensurate with the histopathologic findings on the RPE extent and thickness. No evidence was found for an accumulation of free retinol. Nearly all of the vitamin A stored in the RPE was esterified. As in normal eyes, the retinyl esters consisted mainly of palmitate mixed with a small proportion of stearate. Eleven-cis retinyl esters were present, although their proportion was lower than that reported for normals. IRBP could not be detected in stained gels of the soluble proteins, or by autoradiography of these gels after treatment with 125I-concanavalin A. These findings suggest that depletion of stored vitamin A, accumulation of free retinol, or deficiency of 11-cis isomer are unlikely to be causative factors in the retinal degeneration examined here. Although the depletion of IRBP seen at this advanced stage might be secondary to the advanced loss of photoreceptors, the authors cannot rule out the possibility that a relative deficiency or abnormality in this protein at earlier disease stages may contribute to the pathogenesis of retinitis pigmentosa. PMID- 4039713 TI - Chaulmoogra oil. PMID- 4039714 TI - X-linked bulbo-spinal neuronopathy of late onset: sporadic case. AB - We describe a sporadic case of a rare form of X-linked bulbo-spinal neuronopathy (BSN) of late onset. This case emphasizes the importance of recognizing the sporadic cases of this X-recessive disease for genetic counselling. PMID- 4039715 TI - [Ichthyosis hystrix with parakeratosis in the form of cornoid lamellae]. AB - We report on a keratinization disorder in four brothers in a family in which members had been affected in three generations. Clinical signs and genetic, histopathologic, autoradiographic and ultrastructural examinations all support the diagnosis of hystrixlike, proliferative ichthyosis with cornoid lamellae and autosomal dominant inheritance. The relationship of the disorder to other hystrixlike genetic keratinization disorders is discussed. PMID- 4039716 TI - Study of trace amounts of U in snuff. PMID- 4039717 TI - Mycotic keratitis in a dog: concurrent Aspergillus sp and Curvularia sp infections. AB - A dog with exposure keratopathy developed secondary bilateral keratitis from which Aspergillus sp and Curvularia sp were identified. Mycotic keratitis, while rare in the dog, should be considered in the differential diagnosis of keratitis. PMID- 4039719 TI - A case of Capgras delusion presenting as a postpartum psychosis. AB - A case is reported of Capgras syndrome arising as the major symptomatologic manifestation of a postpartum psychosis. Other diagnostic investigations have called into question the most recent etiopathogenetic interpretations which preclude the concomitant existence of an organic disorder, previously held to be a precondition for the development of Capgras syndrome. PMID- 4039718 TI - Alterations of testicular function induced by hyperprolactinemia in the rat. AB - The effects of hyperprolactinemia on testicular structure and pituitary-gonadal function were investigated in male rats. Hyperprolactinemia was induced in the Wistar-Furth rat by implantation of tissue fragments of a prolactin-secreting MtTW15 pituitary adenoma. The MtTW15 tissue was maintained in one animal group for 27 days (group A) and in another group for 37 days (group B). Appropriate age matched controls were utilized in each study. Serum prolactin was significantly elevated (P less than 0.001) in both groups of MtTW15-bearing rats compared with their controls. The degree of hyperprolactinemia was more severe in rats of group B (2842 +/- 546 ng/ml) than in rats of group A (367 +/- 38 ng/ml). Accessory sex organ weights in group B rats were significantly lower than in controls, but were apparently unaffected in group A rats. Hyperprolactinemia induced definite but variable testicular alterations in both animal groups that presented as seminiferous epithelial disorganization, germ cell exfoliation, increased tubule wall thickness, and abnormal Leydig cell lipid content. Electron microscopy revealed structural disruption of Sertoli-germ cell junctional complexes and apical Sertoli cell cytoplasmic degeneration. The hyperprolactinemic rat exhibited significant reductions in serum luteinizing hormone (LH), testosterone (T), and androgen binding protein (ABP) when compared with controls. Eighty-six days following surgical removal of the MtTW15 tissue in a subgroup of group B rats, serum levels of prolactin and LH returned to normal, as did weights of accessory sex organs and testicular morphology. These results indicate that exposure to the MtTW15 adenoma and its later removal in the rat provides a workable model for studying the effects of hyperprolactinemia on testicular structure and function, and for identifying events involved in the subsequent recovery of spermatogenic disruption. PMID- 4039720 TI - Three-dimensional image analysis of the complex of thin filaments and myosin molecules from skeletal muscle. IV. Reconstitution from minimal- and high-dose images of the actin-tropomyosin-myosin subfragment-1 complex. AB - Three-dimensional images of the actin-tropomyosin-myosin subfragment-1 (S1) complex were reconstituted from both minimal- and high-dose electron micrographs by using a conventional reconstruction technique. Higher resolution (1/15 A-1) than those of the previous reconstructions was attained. A multi-domain structure similar to that of the actin-S1 complex described in the previous paper (1) was observed and a ne diagram of the multi-domain structure of the actin-tropomyosin S1 complex is presented. The shape of S1 molecules in the rigor complex was clearly resolved. In a view perpendicular to the filament axis, S1 had an axially bent profile; only the tail portion, which was thin but was not small in diameter, was steeply inclined. These features were more prominent in the model from minimal-dose images than that from high-dose images. PMID- 4039721 TI - Three-dimensional image analysis of the complex of thin filaments and myosin molecules from skeletal muscle. V. Assignment of actin in the actin-tropomyosin myosin subfragment-1 complex. AB - To assign the actin molecule in the three-dimensional image of the actin tropomyosin-myosin subfragment-1 (actin-TM-S1) complex, the three-dimensional image of the actin-tropomyosin complex was correlated to that of actin-TM-S1. To assess the similarity of two structures in a quantitative manner, we used a normalized cross-correlation function ("similarity function"). The calculation of similarity indicated that domain A and domain B defined in (1, 2) correspond to actin-tropomyosin. This assignment indicates that one S1 molecule strongly interacts with only one actin molecule, but at least two regions of S1 contribute to the binding. Comparison of the reconstituted models of thin filaments with those of decorated thin filaments suggested a change in the shape of the actin molecule. PMID- 4039722 TI - Electrostatic deformation of DNA by a DNA-binding protein. AB - Complementary electrostatic interactions between negatively charged B-DNA and a positively charged array on the lambda Cro repressor protein are shown to substantially contribute to the formation energy of sequence-specific and nonspecific Cro-DNA complexes. The electrostatic interactions favor Cro binding to a bent form of DNA, a geometry which optimizes hydrogen-bonding contacts between Cro and exposed base pair groups in the DNA major groove. PMID- 4039723 TI - Selective regulation of carboxypeptidase peptide hormone-processing enzyme during enkephalin biosynthesis in cultured bovine adrenomedullary chromaffin cells. AB - Bovine adrenomedullary chromaffin cells in culture were incubated with reserpine or forskolin, two agents acting through different mechanisms, which increase cellular [Met]enkephalin levels by 2-fold after 72 h. Cells were harvested and chromaffin granules were purified on a linear sucrose gradient. After reserpine treatment, carboxypeptidase-processing enzyme specific activity in chromaffin granule fractions was stimulated 1.9-fold, and Co2+-stimulated carboxypeptidase specific activity was stimulated 3-fold. The increase in enzyme activity was dependent on the time of reserpine treatment. Forskolin, on the other hand, had no significant effect on carboxypeptidase activity. The differential effects of reserpine and forskolin suggest that the carboxypeptidase-processing enzyme may be selectively regulated during periods of elevated enkephalin formation. Kinetic studies revealed that in cells exposed to reserpine, the Km value for [Met]enkephalin-Arg6 for the Co2+-stimulated carboxypeptidase activity was lowered to 0.136 from 0.447 mM, but there was no change in the Km values of the non-Co2+-stimulated carboxypeptidase activity from reserpine and control groups. Cellular levels of immunoreactive carboxypeptidase-processing enzyme, measured by a radioimmunoassay method, were not altered after reserpine treatment. These data suggest that while the total number of carboxypeptidase enzyme molecules remained constant, there may be a conversion of existing enzyme molecules to a more active form which displays a higher affinity for [Met]enkephalin-Arg6 in the presence of Co2+. PMID- 4039724 TI - Inhibition of testicular cytochrome P-450-dependent steroid biosynthesis by cis platinum. Reversal by human chorionic gonadotropin. AB - The treatment of rats with cis-platinum for 7 days caused a profound, and seemingly selective, decrease (70-80%) in the microsomal cytochrome P-450 levels in the testis. This decrease was accompanied by marked reductions (70-80%) in steroid 17 alpha-hydroxylase activity and in plasma testosterone concentration. The treatment of rats with human chorionic gonadotropin partially restored the cytochrome P-450 concentration and 17 alpha-hydroxylase activity and permitted the plasma testosterone level to approach control values. The effect of cis platinum on the testicular cytochrome P-450 appeared unrelated to deficiencies in heme metabolic processes, in so far that neither was the activity of delta aminolevulinate synthetase decreased, nor was that of heme oxygenase increased. These enzymes are rate-limiting in heme biosynthesis and degradation pathways, respectively. Also, the activities of uroporphyrinogen I synthetase, delta aminolevulinate dehydratase, and ferrochelatase and the concentration of total porphyrins in the testis remained unchanged. The sodium dodecyl sulfate-gel electrophoresis of the microsomal preparation did not reveal a diminished level of apocytochrome; however, in this preparation, heme could not be detected in molecular weight regions corresponding to cytochrome P-450. The microsomal cytochrome b5 and the mitochondrial heme concentrations were not decreased in cis platinum-treated rats. It is suggested that the mechanism of depletive action of cis-platinum on microsomal cytochrome P-450 involves an impairment of the effective assembly of heme and apoprotein moieties. It is further suggested that the anterior pituitary hormones control the factor(s) involved in this assembly, a process which is interrupted by cis-platinum. PMID- 4039725 TI - Coordinate expression of ribosomal protein mRNAs following auxin treatment of soybean hypocotyls. AB - Nine recombinant plasmids containing soybean (Glycine max. var. Wayne) ribosomal protein mRNA sequences were identified by hybrid selection-translation followed by gel electrophoresis. Individual plasmids were used to determine the amount of ribosomal protein mRNA in soybean hypocotyls at various times after application of the synthetic auxin (2,4-dichlorophenoxy)acetic acid. Results from these experiments indicate that the relative abundance of ribosomal protein mRNAs increases 3-8-fold within 24 hr of (2,4-dichlorophenoxy)acetic acid application. Earlier in vitro translation data (Gantt, J. S., and Key, J. L. (1983) Biochemistry 22, 4131-4139) also indicated that the ribosomal protein message levels increase following treatment with auxin. However, the two methods of quantifying mRNA lead to significantly different values for the amount of induction for three ribosomal protein mRNAs. The cause of these differences is not known. An increase in the level of the ribosomal protein mRNAs can be detected 1 h after treatment with (2,4-dichlorophenoxy)acetic acid. The similar kinetics of induction of these messages suggests that their levels are coordinately regulated. PMID- 4039726 TI - Induction of fibrinolytic activity in HeLa cells by phorbol myristate acetate. Tissue-type plasminogen activator antigen and mRNA augmentation require intermediate protein biosynthesis. AB - The highly increased fibrinolytic activity of HeLa cells, treated with the tumor promoting phorbol ester, phorbol myristate acetate (PMA), correlates with equally increased levels of tissue-type plasminogen activator (t-PA) antigen in the conditioned media of these cells and concomitantly increased steady state levels of t-PA-specific mRNA. The effect of PMA on t-PA mRNA levels is completely blocked by pretreatment of the cells with the inhibitor of translation, cycloheximide, indicating that it requires the biosynthesis of at least one protein intermediate. In contrast, mRNA of the oncogene product c-myc can be induced for a brief period immediately following serum starvation in the presence and absence of PMA, and in the presence of cycloheximide. Our results suggest that increased t-PA biosynthesis in HeLa cells, probably through an increased rate of translation of the t-PA gene, forms part of the "late" events of the pleiotropic response to tumor promoters. PMID- 4039727 TI - Active site-directed photoaffinity labeling and partial characterization of oligosaccharyltransferase. AB - Oligosaccharyltransferase, the enzyme that catalyzes the transfer of the oligosaccharide chain of dolichol-P-P-GlcNAc2Man9Glc3 to asparagine residues in Asn-X-Thr/Ser- sites within polypeptides, has been radiolabeled using a photoactivatable azido tripeptide acceptor, N alpha-[3H]Ac-Asn-Lys(N epsilon-p azidobenzoyl)-Thr-NH2. As determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, the molecular mass of the oligosaccharyltransferase polypeptide from hen oviduct microsomes is 60 kDa. Radiolabeling of the 60-kDa polypeptide was completely dependent upon photolysis of hen oviduct endoplasmic reticulum preparations in the presence of the azido peptide and Mn2+, which is required for enzymatic activity. Labeling of the enzyme was not inhibited in the presence of a 10-fold excess of the nonacceptor peptides, unacetylated Asn-Lys(N epsilon-p azidobenzoyl)-Thr-NH2 or unacetylated Asn-Leu-Thr-NH2, whereas it was completely abolished by the presence of a 10-fold excess of the competing acceptor peptide, N alpha-Bz-Asn-Leu-Thr-NH2. Thermal inactivation of oligosaccharyltransferase was achieved by heating endoplasmic reticulum preparations to 60 degrees C. This loss of enzyme activity at 60 degrees C paralleled a comparable decrease in radiolabeling of the 60-kDa polypeptide, whereas temperatures of 50 degrees C and lower had no effect on either process. Oligosaccharyltransferase itself may be an N-linked glycoprotein, because the 60-kDa radiolabeled polypeptide binds to concanavalin A-agarose and is susceptible to digestion by beta-endohexosaminidase H. PMID- 4039728 TI - The primary structure of rat liver cellular retinol-binding protein. AB - The complete amino acid sequence of a cellular retinol-binding protein (CRBP) has been determined for the first time. The primary structure of rat liver CRBP was elucidated by analyses of cyanogen bromide fragments and peptides obtained by tryptic and thermolytic digestions. The single polypeptide chain of rat CRBP consists of 134 amino acid residues. Under reducing conditions, CRBP exists as a monomer, but, in the absence of reducing agents, dimers and multimers of the protein emerge. This is explained by the observation that CRBP contains 3 cysteines, one of which seems to be highly reactive. Whether CRBP contains a disulfide bond is not yet established. The present data extend the previously described homology between CRBP and a family of low molecular weight proteins, all members of which may bind hydrophobic ligands. Since some of these proteins apparently display intracellular transport functions, a similar role for CRBP is envisaged. PMID- 4039730 TI - Chromatographic analysis of choline and acetylcholine by UV visualization. PMID- 4039729 TI - Purification of a multipotential colony-stimulating factor from pokeweed mitogen stimulated mouse spleen cell conditioned medium. AB - A factor able to stimulate the proliferation and differentiation of multipotential stem cells and progenitor cells of the granulocyte-macrophage, eosinophil, and erythroid lineages as well as being able to maintain factor dependent cell lines in culture has been purified from pokeweed mitogen stimulated mouse spleen cell-conditioned medium. The factor was purified over 2 million-fold by sequential fractionation using salting out chromatography, chromatography on phenyl-Sepharose, gel filtration on Sephadex G-75, ion exchange chromatography on DEAE-Sepharose, reverse-phase high performance liquid chromatography on a phenyl-silica column, and gel permeation high performance liquid chromatography. All of the biological activities ascribed to the multipotential colony-stimulating factor co-fractionated through all steps, and the other known mouse-active hemopoietic regulator in pokeweed mitogen-stimulated mouse spleen cell-conditioned medium, granulocyte-macrophage colony-stimulating factor, was separated at the ion exchange step. Two protein species having Mr = 24,000 and 19,000 were visualized by silver-staining of sodium dodecyl sulfate polyacrylamide gels of the purified factor. Both species migrated coincidently with the biological activities. The factor was active at a half-maximal concentration of 1 X 10(-13) M when assayed on a factor-dependent cell line. PMID- 4039731 TI - Screening of pregnant women and hepatitis B prophylaxis in newborns. AB - Prevention of perinatal hepatitis B includes: (1) screening of pregnant women for hepatitis B surface antigen, and (2) immunoprophylaxis of babies at risk. HBIG treatment seems to be of some efficacy in preventing the HBsAg carrier state while it permits passive active immunization to occur. The disadvantage of HBIG is that it confers only temporary immunity. Therefore, if infection does not occur, babies will still be susceptible to the virus when passively administered anti-HBs will no longer be circulating. On the other hand, vaccine provides a long term but not immediate protection. Therefore the ideal approach in post exposure prophylaxis is a combination of passive plus active immunization. The aim is to provide an immediate protection, with the HBIG, and a long term immunity, with the vaccine, to babies born to HBsAg carrier mothers. PMID- 4039732 TI - Somatomedin-C levels in children and adolescents with gonadal dysgenesis: differences from age-matched normal females and effect of chronic estrogen replacement therapy. AB - The factors responsible for the elevation of circulating somatomedin-C/insulin like growth factor I (Sm-C) during normal pubertal development are uncertain. To assess the role of ovarian estrogen secretion during puberty, we examined the effect of estrogen deficiency due to primary hypogonadism on Sm-C levels in late childhood and early adolescence. The concentration of immunoreactive Sm-C was measured in 36 untreated patients with gonadal dysgenesis (age, 4-16 yr); results were compared with the pattern of change in Sm-C in 153 age-matched normal girls. Between ages 4-9 yr, patients with gonadal dysgenesis had Sm-C levels similar to those in the age-matched normal subjects. In contrast to the normal girls, Sm-C levels in patients with gonadal dysgenesis did not rise after 10 yr of age and were significantly lower than those in normal girls at 11-16 yr of age. The effect of low dose estrogen therapy was assessed in eight patients with Turner's syndrome. Their Sm-C levels were measured before and during 2-12 months of treatment with ethinyl estradiol (90-220 ng/kg X day). The mean Sm-C concentration rose from 0.72 +/- 0.06 U/ml (+/- SEM) before treatment to 1.17 +/- 0.17 U/ml during estrogen treatment (P less than 0.04). In three patients who had a similar increase in Sm-C during estrogen treatment, interruption of therapy was associated with a fall in Sm-C concentrations; when estrogen therapy was reinstituted in two of these patients, Sm-C levels rose again. These results suggest that increasing endogenous estrogen production is a major determinant of the rise of circulating Sm-C that occurs during pubertal development in normal girls. Chronic estrogen deficiency, as in untreated patients with gonadal dysgenesis, is associated with failure to manifest the elevation of Sm-C that occurs during normal puberty. PMID- 4039733 TI - Plasma steroid-binding proteins in the cysts of gross cystic disease of the breast. AB - Breast cyst fluids from 33 patients who underwent cyst aspiration were examined for their content of total protein, albumin, corticosteroid-binding globulin (CBG), and testosterone-estradiol-binding globulin (TeBG). Two distinct populations of cysts, based on their chloride concentration, were found. Both types of cysts had markedly reduced concentrations of the three plasma proteins compared to plasma levels. Concentrations of the proteins in the low chloride (less than 40 meq/liter) cysts were substantially lower than those in the high chloride (greater than 40 meq/liter) ones. Relative to albumin, both CBG and TeBG were excluded from low chloride cysts, whereas relative to one another, the ratios of these two steroid-binding proteins were the same as those in plasma. We conclude that there are specific mechanisms in breast cysts regulating the ingress and/or egress of CBG and TeBG. PMID- 4039735 TI - Postirradiation angiosarcoma. AB - A 61-year-old woman developed a cutaneous angiosarcoma of the lower abdomen in the site where she had received radiotherapy for squamous cell carcinoma of the cervix uteri 23 years earlier. The rarity of this event and the dermatologist's general unfamiliarity with this late complication of radiation therapy have prompted a review of cutaneous postirradiation angiosarcoma. PMID- 4039734 TI - Polymorphism of theophylline metabolism in man. AB - To determine whether genetic mechanisms control large interindividual variations in theophylline elimination in normal uninduced human subjects, and, if so, to test the possibility that these genetic factors are transmitted as a simple Mendelian trait, theophylline was administered to 79 unrelated adults, six sets of monozygotic twins, six sets of dizygotic twins, and six two-generation families. Thereafter, in urine collected from each subject at regular intervals for 48 h, concentrations of theophylline and its three principal metabolites were measured and rate constants of formation of these metabolites calculated. The twin study, designed to determine the relative contributions of genetic and environmental factors to large interindividual variation in theophylline elimination, revealed predominantly genetic control. Values for this genetic component, designated heritability (H1(2)), of interindividual variation in rate constants of metabolite formation were 0.61, 0.84, and 0.95 for 3-methylxanthine, 1-methyluric acid, and 1,3-dimethyluric acid, respectively. H1(2) for the overall theophylline elimination rate constant (kel) was lower (0.34). In the 79 unrelated adults, each distribution curve for rate constants of formation of each theophylline metabolite appeared to be trimodal. By contrast, the distribution curve for the overall theophylline elimination rate constant appeared to be either unimodal or bimodal. The extent of interindividual variation was fourfold for theophylline kel and 6-8-fold for the three principal metabolites. High correlations among the three rate constants in individual subjects suggested their regulation by a single shared factor. In six families carefully selected to be under near basal environmental conditions so that hepatic theophylline metabolism of each family member would be neither markedly induced nor inhibited, phenotypes for theophylline metabolite rate constants were assigned. This assignment of phenotype was made by the position of each family member's rate constant on the three distribution curves that were generated from the 79 unrelated subjects. In each family, pedigree analysis of the three phenotypes for each rate constant was consistent with their control by two alleles at a single genetic locus and with autosomal codominant transmission. Frequencies of the two alleles at each genetic locus controlling rate constants of formation of theophylline metabolites were similar (p = 0.49, 0.53, and 0.52). In the three families studied with antipyrine (AP) as well as with theophylline, AP k(el) correlated (r approximately 0.7) with each rate constant of theophylline metabolite formation, as well as with theophylline k(el). While these results are compatible with a common regulatory element in the AP and theophylline polymorphisms, other evidence suggests more than a single genetic polymorphism. This additional evidence includes different gene frequencies for the AP (p approximately 0.1) and theophylline (p approximately 0.5) polymorphisms, different genotype assignments in several families for some theophylline metabolites, different distribution curves for theophylline k(el) from those for the three theophylline metabolites in 79 unrelated subjects, and finally low correlations between AP metabolite rate constants and theophylline metabolite rate constants in the three families receiving both drugs. PMID- 4039736 TI - Prognostic factors of severe infectious purpura in children. AB - The French Club of Pediatric Intensive Care has prospectively studied 90 cases of infectious purpura which were hospitalized in 1981; the purpose of this study was to determine prognostic factors. The statistical study (X2 test) of all these cases is in agreement with data in the literature and shows that the mortality is significantly higher when there is: shock (p less than 0.001), coma (p less than 0.05), ecchymotic or necrotic purpura (p less than 0.01), temperature less than 36 degrees C (p less than 0.05), no clinical meningism (p less than 0.001), white cell count less than 10,000/mm3 (p less than 0.05), thrombocytopenia less than 100,000 (p less than 0.01), fibrinogen less than 1.5 g/l (p less than 0.001), kalemia greater than 5 mEq/l (p less than 0.01), spinal fluid cell count less than 20/mm3 (p less than 0.01). Because shock is one of the main prognostic factors (23 deaths in 55 shocked patients, versus 2 in 35 non-shocked) we have performed another statistical study (with the Benzecri method) to determine a prognostic index for patients in shock. For its determination, five initial parameters are used: age, kalemia, white cell count, clinical meningism, platelet count. The predictive value for survival is 91%. The predictive value for death is 87%. The score was applied on the patients hospitalized in shock in 1982: the predictive value for survival is 75%, the predictive value for death is 61%. PMID- 4039737 TI - Respondent conditioning of self-injurious behavior in early socially deprived rhesus monkeys (Macaca mulatta). PMID- 4039738 TI - Primary cardiac tumors: experience with 30 consecutive patients since the introduction of two-dimensional echocardiography. AB - Experience with 30 consecutive patients who had a total of 32 primary cardiac tumors and who underwent two-dimensional echocardiographic examinations between January 1977 and June 1983 was reviewed. Most of the tumors were atrial myxomas (20 left and 4 right), and 30 were identified on echocardiography. Twenty-five patients, including 21 of 22 with atrial myxoma, underwent surgical resection on the basis of the echocardiographic examination, without preoperative angiocardiography. When the morphologic characteristics of the left atrial myxomas were studied statistically in relation to clinical abnormalities, large tumor size was most closely related to the number and type of associated clinical and laboratory abnormalities. The single exception was embolization, which correlated with echocardiographic tumor consistency. Since the introduction of two-dimensional echocardiography, the yearly incidence of cardiac tumor diagnosis at this clinic has increased several fold and the incidence of unexpected intraoperative diagnosis has been very low (one case). Echocardiography is the method of choice for clinical diagnosis. It has replaced angiocardiography for routine preoperative assessment, permits early diagnosis of cardiac neoplasms and provides insight into the pathophysiology of primary cardiac tumors. PMID- 4039739 TI - Role of the autonomic nervous system in the control of heart rate and blood pressure in the defence reaction in conscious dogs. AB - The present study was performed on conscious, chronically instrumented dogs, which underwent selective blockade of sympathetic adrenergic and vagal outflows. Excitements were performed on these animals in normal states (N), after chronic treatment with guanethidine, for sympathetic blockade (SB), after cold vagal blockade (VB), and after combined sympathetic and vagal blockade (SB + VB). Heart rate and arterial blood pressure were monitored in all the experiments, while a group of dogs was also tested with an electromagnetic flowmeter on the superior mesenteric artery. The role of the sympathetic and parasympathetic controls in the defence reaction was assumed from comparison of experiments performed in the presence or in the absence of each (or both) autonomic component(s). In the SB + VB condition, excitement was followed by sudden hypotension, without changes in heart rate. In VB experiments, a brief and transient hypotension appeared, followed by gradually developed hypertension, while heart rate progressively rose in about 5 s; there was no sudden increase in mesenteric vascular resistance, which contrasted with the very marked reaction in N experiments. Under vagal control alone (SB), the stimulus elicited prompt tachycardia and hypertension, followed by a period of moderately reduced blood pressure. We conclude that, while the defence reaction leads to a sudden fall of arterial blood pressure, in the absence of compensatory mechanisms, both branches of the autonomic nervous system play a protective role against hypotension. In addition, the modulation of the vagal outflow, leading to sudden changes in the heart performance, seems to be responsible for the initiation of the overall haemodynamic adjustments following excitements. The possibility that withdrawal of the parasympathetic outflow to the heart may raise arterial blood pressure was verified in a special experiment in which artificial vagal stimulation in a conscious (vagal blocked) dog, was turned off for brief periods, before and after guanethidine. This led to changes in blood pressure and heart rate very similar to those seen at the onset of the defence reaction, both in N and SB conditions. PMID- 4039740 TI - Induction of infectious immunodeficiency in BALB/c mice by serial transfer of lymphocytes immune to alloantigens. AB - Serial transfer of spleen cells immune to allogeneic or semi-allogeneic cells induced transferable splenomegaly and general immune deficiencies, including the lack of proliferative responses to T and B cell mitogens and antibody responses to specific antigens. Parallel experiments with spleen cells from mice that had been administered rectally with allogeneic spleen or sperm cells also resulted in a similar immunodeficiency. The immune deficiencies were transferable into normal mice by injection of spleen cells, cellfree extracts, or culture supernatants of spleen cells from immunodeficient mice. The particle responsible for transmission of immunodeficiency appears to be a high m.w. (greater than 2 X 10(6], 1.14 g/ml density agent. These results suggest strongly that serial transfer of lymphocytes immune to alloantigens triggers the release of a transmissible virus-like agent, which results in an immunodeficiency similar to acquired immune deficiency syndrome (AIDS) of humans. Therefore, this system may provide a valuable animal model system for studying AIDS. PMID- 4039741 TI - Evaluation of anchoring fibrils and other components of the dermal-epidermal junction in dystrophic epidermolysis bullosa by a quantitative ultrastructural technique. AB - To examine the possibility that differences in the structure and population density of anchoring fibrils (AF) and other components of the dermal-epidermal junction might distinguish between genetically and clinically distinct varieties of dystrophic epidermolysis bullosa (DEB), a controlled ultrastructural morphometric study of nonseparated keratinocyte-associated dermal-epidermal junction was undertaken in a total of 17 patients with DEB. Seven patients had dominant DEB, 3 had localized recessive DEB, and 7 had severe, generalized recessive DEB. Nonlesional, unscarred skin was obtained from standard body regions. Criteria for the identification of AF were a mandatory union with the lamina densa and the presence of central banding and/or fanning of the extremities. No AF were detected in 9 technically suitable samples from patients with severe recessive DEB. Structurally normal AF were present, but significantly reduced in number, in both dominant and localized recessive DEB, compared with site-matched samples from 12 healthy adults. There was no difference in AF characteristics between dominant and localized recessive DEB, or between sites of predilection and nonpredilection for blisters. The presence or absence of albopapuloid lesions in dominant DEB did not influence AF counts. There was no difference in numbers of hemidesmosomes, basal cell plasmalemmal vesicles, or dermal microfibril bundles in any group of DEB patients compared with controls. Thus, although severe mutilating DEB can be distinguished by routine transmission electron microscopy, the dominant and localized recessive forms cannot be differentiated on the basis of AF structure or numbers. PMID- 4039742 TI - [Effect, toxicity and tissue concentration in the clinical use of cis diamminedichloroplatinum (II)]. AB - The tissue cis-diamminedichloroplatinum (II) (CDDP) concentration was measured in autopsies treated with CDDP therapy for gynecological malignancies. These cases consisted of 10 of ovarian tumor and one of choriocarcinoma. Total CDDP doses administered were from 55mg to 560mg and among them three cases were treated with more than 500mg (525mg, 555mg in ovarian cancer and 560mg in choriocarcinoma). We found moderate renal impairment with this drug by serum functional test and histopathology, although these changes did not correspond with the total doses. In liver, kidney and residual tumor measured for CDDP, the tissue concentration was highest in liver. When total doses administered were compared with the tissue concentration in liver, kidney, residual tumor and the decrease in creatinine clearance value, there were statistically significant differences only in residual tumor at p less than 0.01. PMID- 4039743 TI - Clinicopathologic investigation of ovarian endometriosis: a comparative study of cystic and non-cystic types. AB - This clinicopathologic study involved 129 patients with ovarian endometriosis. All the lesions from the patients were classified macroscopically into two types being either cystic or non-cystic. The results are as follows. Endometriotic lesions were bilateral in 58 cases and unilateral in 71 cases. The average age of the patients was 38.8 and gravidity 1.8, with 43.1% of them being infertilite. In 12.2, 45.4 and 84.6% of them, irregular menstruation, hypermenorrhea, and dysmenorrhea were recorded, respectively. Regarding complicated lesions, 49 patients had fibroid, 33 uterine adenomyosis, and 13 rectocervical endometriosis. Of the 129 cases, 61.3% were regarded as of the cystic type, 30.2% as of the non cystic type, and 8.5% as of the cystic/non-cystic type. The average ages were 35.5 and 41.6 years for cystic and non-cystic types, respectively. The incidence of each type of complicated lesion mentioned above was greater in the non-cystic type than that in the cystic type. The pathogenetic investigation suggested that cystic endometriosis in the ovary might mainly be ascribed to the endometrioid metaplasia of the celomic epithelium and that non-cystic endometriosis might occasionally originate from metastasis or implantation of endometrial tissues. In addition to this, the lesions which were histologically diagnosed as endometriosis might sometimes include obsolete follicle cysts undergoing luteinization. PMID- 4039744 TI - Influence of vitamin D on mineral metabolism, hormonal status and bone histology in lactating rats and their pups. AB - Mineral, hormonal and skeletal changes were determined in vitamin D-deficient ( D) and vitamin D-replete (+D) mother rats and in their litters on day 20 of lactation. These results were compared with those obtained in -D mothers and pups, after giving the mothers an oral supplement (10 i.u. vitamin D3/day) during the period of lactation (20 days). Compared to +D animals, both -D lactating mothers and their pups exhibited extremely low plasma levels of 25-hydroxyvitamin D3 (25-OH-D3), diminished 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) and increased levels of immunoreactive parathyroid hormone (iPTH). Vitamin D-deficient mothers also had higher levels of calcitonin and lower levels of prolactin than +D mothers. All -D animals (mothers and pups) showed increased osteoclastic bone resorption and severe osteomalacia as shown by decreased bone ash, decreased calcification rate and increased endosteal osteoid surface, volume and thickness. In mothers treated with vitamin D3 during lactation, nearly all the plasma variables measured, as well as bone histomorphometric features, were normal. In contrast, their pups still showed rickets and osteomalacia, despite normal levels of 25-OH-D3 and calcium in the plasma. These pups had raised plasma levels of 1,25(OH)2D3 and iPTH associated with persistent stimulation of bone resorption. This study showed that (1) severe vitamin D deficiency in lactating rats produced marked osteomalacia and secondary hyperparathyroidism in both mothers and pups, and (2) vitamin D treatment of -D mother rats during lactation (10 i.u. vitamin D3/day) reversed the mineral, hormonal and skeletal abnormalities in mothers but not in pups. PMID- 4039745 TI - Somatic and germ cell chimerism in chimeric mice between strains of high litter size and regular litter size. AB - CFO is an inbred strain of mice showing a high litter size. The high fertility of CFO is due mainly to a very low embryonic death rate during uterine development. C57BL and 129 strains are characterized by regular litter size. Crosses were made and CFO----C57BL and CFO----129 chimeras were produced. In CFO----C57BL mice, coat color of the C57BL predominated over that of CFO; internal chimerism except for that of the gonads was observed to be in the same proportion as the two genotypes, but the genotypic component of the gonads was almost entirely CFO. Germ cells undergoing gametogenesis in the CFO----C57BL mice were almost all derived from the CFO genotype, and the chimeric females showed high fertility just as did the CFO females. In the CFO----129 mice no obvious skewing toward one genotype was observed in the coat color, but the germ cells undergoing oogenesis in the two types of chimeric females were recognizable as nearly all of the 129 genotype but with the females showing the same high fertility as do the CFO females. This fact suggests that the genotypes of germ cells in the ovary or in developing embryos do not influence fertility, but rather that the litter size is controlled mainly by the uterine environment. PMID- 4039746 TI - Detectability of group-specific component (Gc) in aged bloodstains. AB - An improved method of group-specific component (Gc) typing was conducted electrophoretically on agarose gel. Individual bloodstains randomly collected from different individual donors over a five-year period at intervals of approximately one month were checked for Gc activity. Group-specific component was typed accurately in dried bloodstains stored at room temperature up to 43 months in age. From 100 different donors, bloodstains ranging in age from 38 to 43 months were tested by the methods described and 73% of the samples were interpretable for Gc. PMID- 4039747 TI - The proteins and RNAs of St. Abb's Head virus, a Scottish Uukuvirus. AB - The proteins and RNAs of St. Abb's Head virus have been analysed, and were found to be characteristic of the Uukuvirus genus of the family Bunyaviridae. Two glycoproteins, G1 and G2 (mol. wt. 62K and 75K), and a nucleocapsid protein, N (mol. wt. 25K), were detected in infected cells by immunoprecipitation; the synthesis of N preceded the synthesis of G1 and G2. The glycoproteins were relatively cysteine-rich compared to the N protein, and the unglycosylated forms of G1 and G2 (using the inhibitor tunicamycin) had a mol. wt. of about 58K. Translation in vitro of mRNA from infected cells gave two immunoprecipitable products which are thought to be equivalent to N and G1/G2. Three RNA species were found in St. Abb's Head virus nucleocapsids, and were estimated to be 8500 bases (L), 3600 bases (M) and 1900 bases (S) in length. At least one additional virus-specific RNA species was detected in infected cells. The similarity between the proteins and RNAs of St. Abb's Head virus and Uukuniemi virus (the prototype of the genus) is discussed. PMID- 4039748 TI - Serum dopamine beta-hydroxylase activity in menstrual migraine. AB - Migraine has been considered a manifestation of sympathetic dysfunction. Serum dopamine beta-hydroxylase (D beta H) has been shown to be an index of peripheral sympathetic activity by some workers and there are two reports of elevated activity of the enzyme during the migraine headache as well as in the headache free interval. We studied the enzyme in seven women complaining of regular attacks of menstrual migraine and eleven controls during the mid-follicular (days 10 +/- 2) and premenstrual (days 28 +/- 2) phases of the menstrual cycle. Although levels were on average 26% and 10% higher respectively than in control subjects, the difference failed to reach statistical significance because of the large normal range for enzyme activity. However, the premenstrual results were significantly lower (p less than 0.001) than the mid-follicular measurements in the migraine group, little difference being found in controls. This finding, and the effects of successful therapy with anovulatory doses of oestradiol implants in not only significantly lowering serum D beta H but also significantly reducing the difference in enzymic activity between the early and late phases of the menstrual cycle, suggest that if this enzyme is an index of sympathetic activity, it is excessive fluctuations of the sympathetic nervous system that may be relevant in menstrual migraine. PMID- 4039749 TI - Rhino-orbital zygomycosis. AB - A 63-year-old diabetic man presented with sinusitis with orbital and intracranial signs progressing over one week, due to zygomycosis. Despite control of the diabetes, surgical excision of infected tissue and antifungal therapy he died in the fifth week of illness. Pathological study showed extensive fungal infiltration of periorbital structures and mycotic thrombosis of many blood vessels with associated necrosis and infarction of fat and extraocular muscles. PMID- 4039750 TI - Antiepileptic and antiamnesic effect of carbamazepine in experimental limbic epilepsy. AB - Carbamazepine (20 mg/kg, 40 mg/kg or 60 mg/kg) given three times a day, has been demonstrated to have a significant anti-epileptic effect in rats with chronic limbic epilepsy induced by injecting tetanus toxin bilaterally into their hippocampi. This effect involved a reduction in the maximum number of fits occurring on one day, and with the highest dose, a significant reduction in the total number of fits. In a pilot experiment in which continuous EEG records were obtained throughout the syndrome, it appeared that the effect of carbamazepine was to reduce the proportion of EEG seizure discharges which lead to overt motor fits. With the higher drug dose plasma levels of carbamazepine were maintained around 2 micrograms/ml. This experimental epilepsy produces enduring deficits in the rats' memories for a light-discrimination task in a Y-maze learned before induction of epilepsy (8 weeks after initial learning). If the rats are dosed with carbamazepine during their epilepsy this memory deficit is abolished. PMID- 4039751 TI - Supraophthalmic carotid infusion for brain chemotherapy. Experience with a new single-lumen catheter and maneuverable tip. AB - A single-lumen catheter with a maneuverable tip which does not incorporate a balloon has been developed for supraophthalmic intracarotid infusion of chemotherapeutic agents for central nervous system neoplasms. Supraophthalmic carotid catheterization was accomplished in 48 (96%) of the first 50 consecutive infusions in which this catheter was used. None of the 31 patients who underwent this procedure developed optic neuropathy or loss of vision. Ten patients developed Marcus-Gunn pupils, ipsilateral to the infused carotid artery in two and contralateral to the infused carotid artery in eight. Thrombosis of the carotid artery occurred after infusion in one patient. Problems associated with the technique include a tendency for the catheter to retract proximally during infusion in some patients, and the necessity for surgical exposure of the carotid artery. The infusion technique protects the eye from the high-concentration first pass of chemotherapeutic agents administered via the carotid artery. Since the tip of this catheter can be hydraulically guided, it may prove to be useful in other areas of transarterial neurosurgical procedures. PMID- 4039752 TI - Differences in somatomedin-C between short-normal subjects and those of normal height. AB - We evaluated basal somatomedin-C (SmC) levels in 98 subjects 2 to 16.6 years of age, with height less than 3rd centile (Tanner), and in 274 healthy controls 2 to 15.8 years, with height greater than 10th centile. Growth-retarded subjects were defined as short-normal when they had normal GH release (greater than 8 ng/ml) in at least one of three tests: arginine, L-dopa, and sleep. In control subjects, there was a significant positive correlation between SmC levels and chronologic age, bone age, and pubertal stage (pubic hair, breast or testicular volume). The same correlations were present in short-normal subjects, but SmC levels were significantly lower than in normal children. The percentage of subjects with very low SmC values (less than or equal to 0.25 IU/ml in those older than 6 years, and less than 0.1 IU/ml in those younger than 6 years) was higher in the short-normal group of children older than 6 years. In growth-retarded subjects, SmC values were significantly higher (P less than 0.005) in subjects with normal GH response in at least one of the two pharmacologic tests, compared with those with normal GH response only during sleep. We conclude that short-normal subjects have, on average, low SmC values, which might indicate insufficient GH release. Therefore, current criteria to define GH deficiency and children needing treatment may be too restrictive. PMID- 4039753 TI - Toluene embryopathy. AB - Three children with microcephaly, central nervous system dysfunction, minor craniofacial and limb anomalies, and variable growth deficiency were born to women who inhaled large quantities of pure toluene throughout pregnancy. The features in our patients were reminiscent of the patterns of malformation previously described following in utero exposure to alcohol, certain anticonvulsants, and hyperphenylalaninemia. It is possible that there is a variable and nonspecific teratogenic phenotype characterized by alterations in growth, development, and morphogenesis. Careful evaluation and monitoring of infants exposed to toluene in utero are needed to determine the significance of our findings. PMID- 4039754 TI - Childhood acute idiopathic thrombocytopenic purpura: how many tests and how much treatment required? PMID- 4039755 TI - Liquid chromatographic-ultraviolet methods for furegrelate in serum and urine: preliminary pharmacokinetic evaluation in the dog. AB - Analytical methods have been developed for the quantitative determination of furegrelate (1), a thromboxane synthetase inhibitor, in dog serum and urine specimens. The methods use ion-pairing reversed-phase high-performance liquid chromatography (HPLC) with UV detection at 268 nm and have the necessary specificity, linearity, and sensitivity to quantitate 100 ng/mL of the drug in serum and 20 micrograms/mL in urine. Preliminary pharmacokinetic and bioavailability evaluations in the dog indicate that 1 was rapidly distributed and had a terminal half-life of 132 min after an intravenous dose. The primary route of elimination was renal with approximately 70% of the parent drug excreted in urine. Fasted dogs dosed orally with the drug in solution or capsule had similar absorption and elimination kinetics and agreed favorably with the intravenous results. The bioavailability of 1 dosed orally was 77-80% based on serum area under curve and greater than 90% based on urinary excretion of the parent compound. The serum kinetics, but not the urinary elimination, of 1 appeared to be altered in fed dogs given drug in capsule. PMID- 4039756 TI - Biochemical correlates of morphine withdrawal. 2. Effects of clonidine. AB - Naloxone-precipitated morphine withdrawal in the rat has been shown to deplete adrenal epinephrine and to increase adrenal and locus ceruleus tyrosine hydroxylase activities. Administration of clonidine (0.1 - 1.0 mg/kg) through the first 6 hr of withdrawal blocked adrenal epinephrine depletion in a dose dependent fashion. Clonidine also blocked the increases in tyrosine hydroxylase activity seen in the adrenal and locus ceruleus during withdrawal. Clonidine attenuated the weight loss and inhibited the diarrhea during withdrawal. The alpha-2 adrenergic antagonist yohimbine reversed the effects of clonidine in blocking withdrawal. Morphine withdrawal caused only a slight depletion of epinephrine in the denervated adrenal; however, clonidine (0.3 mg/kg) prevented this decrease. These results suggest that clonidine suppresses adrenal and central adrenergic function during morphine withdrawal. This effect occurs through an alpha-2 adrenergic mechanism, possibly at the level of the locus ceruleus although clonidine appears to also have a direct effect on the adrenal medulla. The results are discussed in terms of adrenergic mechanisms of opiate withdrawal and the actions of clonidine on this syndrome. PMID- 4039757 TI - Management of a harem breeding colony of rhesus monkeys to reduce trauma-related morbidity and mortality. AB - A management procedure was developed for a harem breeding colony of rhesus monkeys to reduce trauma-related injuries and deaths resulting from the periodic removal of pregnant monkeys for research and their subsequent return to the population. Lower morbidity and mortality rates, a reduced mean conception interval, and a higher mean conception rate occurred when monkeys were maintained in permanent harems to which returning females were reintroduced compared to new social groups formed from aggregates of unfamiliar animals. PMID- 4039758 TI - Asymmetrical binding of phloretin to the glucose transport system of human erythrocytes. AB - The sidedness of phloretin binding to the glucose carrier has been determined by comparing the type of inhibition produced in zero trans entry and zero trans exit experiments. Initial rates of zero trans entry were measured by the method of R.D. Taverna and R.G. Langdon (Biochim. Biophys. Acta 298:412-421, 1973), which involves pink ghosts loaded with glucose oxidase; this obviates the problem of rapid substrate accumulation inside the cells. With phloretin equilibrated across the membrane, the inhibition of entry was competitive, and the inhibition of exit noncompetitive. The experimental procedures were validated by showing that the inhibition by cytochalasin B, known to bind inside but not outside, was noncompetitive in entry and competitive in exit, as predicted. It was also demonstrated that even after pre-incubation of the cells with a relatively high concentration of phloretin, the phloretin adsorbed in the membrane did not significantly alter the rate of carrier reorientation. The results show that the outward-facing form of the glucose carrier, but not the inward-facing form, bears a phloretin binding site; thus phloretin, as well as cytochalasin B, is bound asymmetrically, phloretin outside and cytochalasin B inside. PMID- 4039760 TI - Structure of short thick filaments from Limulus muscle. AB - Shortened Limulus thick filaments, isolated from stimulated muscle, are structurally similar to long filaments, isolated from unstimulated muscle, except for length. Both have 3-fold screw symmetry with a helical repeat at approximately 43 nm, axial spacing of 14.5 nm between successive crowns of crossbridges and 4-fold rotational symmetry as estimated from the Bessel argument, by analysis of optical transforms of electron micrograph negatives of negatively stained samples. Both short and long filaments also have similar radii for the location of their crossbridges, thus similar diameters. Equal numbers of subunits/helical strand are also apparent on images of metal-shadowed long and short filaments. Since these data argue against molecular reorganization during filament shortening, it is suggested that the change in length of Limulus thick filaments may occur by reversible disaggregation of constituent protein molecules. PMID- 4039759 TI - Reaction of the glucose carrier of erythrocytes with sodium tetrathionate: evidence for inward-facing and outward-facing carrier conformations. AB - Sodium tetrathionate reacts with the glucose carrier of human erythrocytes at a rate which is greatly altered in the presence of competitive inhibitors of glucose transport. Inhibitors bound to the carrier on the outer surface of the membrane, either at the substrate site (maltose) or at the external inhibition site (phloretin and phlorizin), more than double the reaction rate. Inhibitors bound at the internal inhibition site (cytochalasin B and androstenedione), protect the system against tetrathionate. After treatment with tetrathionate, the maximum transport rate falls to less than one-third, and the properties of the binding sites are modified in unexpected ways. The affinity of externally bound inhibitors rises: phloretin is bound up to seven times more strongly and phlorizin and maltose twice as strongly. The affinity of cytochalasin B, bound at the internal inhibition site, falls to half while that of androstenedione is little changed. The affinity of external glucose falls slightly. Androstenedione prevents both the fall in transport activity and the increase in phloretin affinity produced by tetrathionate. An inhibitor of anion transport has no effect on the reaction. The observations support the following conclusions: Tetrathionate produces its effects on the glucose transport system by reacting with the carrier on the outer surface of the membrane. The carrier assumes distinct inward-facing and outward-facing conformations, and tetrathionate reacts with only the outward-facing form. The thiol group with which tetrathionate is presumed to react is not present in either the substrate site or the internal or external inhibitor site.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4039761 TI - Cell surface and cytokinetic structures in cell shape determination of mouse fibroblasts. Events involved in cell rounding induced by removal of loosely bound macromolecular moieties from the cell surface. AB - Cell rounding was induced in synchronised mouse embryo fibroblasts without the use of drugs by a new method based on removal from the cell surface of loosely bound macromolecular moieties. The cells were examined by scanning and transmission electron microscopy and also by specific fluorescence methods during experimentally induced progression from the spread to a rounded form to assess changes in the cell surface and in the arrangement of cytoskeletal elements. Early events were a loss of order in the subcortical microfilament network and the formation of surface blebs. This was followed by disintegration of stress fibres and body retraction. Microtubules and intermediate filaments maintained their integrity but moved inwards towards the rounded perinuclear part of the cells. The relationship between surface alterations, organisation of the cytoskeleton and cell conformation is discussed. PMID- 4039762 TI - Vasography: effect of various agents on vas deferens patency. AB - Vasography is a common diagnostic procedure utilized in evaluating the male genital tract for causes of azoospermia, for evaluation of persistent perineal pain and seminal vesiculitis, and recently used in the staging of prostate cancer. In order to evaluate the effects of injectable agents on the healthy vas deferens, 7 groups of 10 rats had the left vas deferens injected by vasopuncture with saline, 4 contrast agents, doxycycline and absolute alcohol. The animals were sacrificed 8 weeks later, and were examined for patency of the vas and inflammatory response. Results revealed that vasopuncture did not produce obstruction. Vasography with water-soluble contrast media does entail a low risk of inflammation in the rat, but produces no obstruction. Intra-vas injection of doxycycline, injected by some for treatment of chronic seminal vesiculitis and perineal pain, is not deleterious in the rat model. PMID- 4039763 TI - Experimental obstructive hydronephrosis in newborn rats. V. Long-term effects on renal tissue solute content. AB - Partial obstruction of 1 ureter was created in newborn rats and its effects were studied in the adult rat. The obstructed renal pelvis was found to be about 6 times enlarged and the weight of the kidney was 85 per cent of the contralateral intact one. Despite considerable distortion of the inner medulla on the obstructed side, no loss of weight in this region was observed. The only changes observed with respect to tissue concentrations--which were significantly due to the obstruction--were increases in urea in the cortex (110 per cent) and in potassium in the inner medulla (21 per cent); thus, the changes were few and, in part, moderate. The findings are compared with previous observations of solute excretions and the pathophysiological implications are discussed. The conclusion is that although the inner medulla was considerably distorted, the solute content was far from being affected to a corresponding degree--at least not in this experimental preparation. PMID- 4039764 TI - Differential effects of prolactin on rat dorsolateral prostate and R3327 prostatic tumor sublines. AB - Many investigators have reported effects of the pituitary hormone, prolactin, on the physiology and biochemistry of the rat prostate gland, particularly the lateral or dorsolateral lobe. The Dunning R3327H is a transplantable rat prostatic adenocarcinoma derived from a spontaneous tumor of the Copenhagen rat dorsolateral prostate. This study describes and compares morphological and physiological effects of prolactin on rat dorsolateral prostate and two sublines of the Dunning tumor. Ectopic pituitary grafts were used to induce chronic hyperprolactinemia in castrated rats receiving androgen supplement to provide a relatively controlled hormonal environment in which the effects of prolactin were maximally and consistently observed. Gravimetric and biochemical analyses, as well as ultrastructural study, provided evidence of prolactin's stimulatory effect on dorsolateral prostate growth and secretory activity. Hyperprolactinemia stimulated the growth of the well-differentiated, androgen-dependent R3327/3219 tumor subline with an increase in weight, volume and the total content of DNA, protein and zinc. There were no changes in tumor morphology. In contrast, the anaplastic androgen-independent R3327/150 tumor subline did not respond to graft induced hyperprolactinemia. This differential response of the two R3327 tumor sublines attests to the complexity of prolactin's effects on prostatic tissue and to the extent of the deterioration of endocrine control that often accompanies tumor progression. Prolactin binding in the R3327 sublines was studied using immunohistochemical staining and radioligand assay, but produced complex results which raise questions about the discrepancy between hormone binding and biological action of prolactin in prostatic tissues. PMID- 4039765 TI - Malignant catarrhal fever in a free-ranging black-tailed deer (Odocoileus hemionus columbianus) in California. PMID- 4039766 TI - Cardiac dimension changes with endurance training. Indications of a genotype dependency. AB - We studied the sensitivity of cardiac structures to endurance training. To evaluate variability in adaptation, 20 sedentary subjects and ten pairs of monozygotic twins were submitted to a 20-week endurance training program. Maximal oxygen uptake increased significantly in both groups: 11 mL O2/kg/min-1 or 30% in the sedentary group and 6 mL O2/kg/min-1 or 13% in the monozygotic twins. Statistically significant increases in left ventricular diameter, posterior wall and septal thicknesses, as well as left ventricular end-diastolic volume and left ventricular mass were observed in the sedentary subjects, but not in the monozygotic twins. We could demonstrate that after training, twin pairs differed more from each other than at the start. Concomitantly, within-pair resemblance was greater after training than before. Results indicate that cardiac dimensions are amenable to significant modifications under controlled endurance training conditions and furthermore that the extent and variability of the response of cardiac structures to training are perhaps genotype dependent. PMID- 4039767 TI - Toxicity associated with long-term intravenous heroin and cocaine self administration in the rat. AB - Laboratory rats were given unlimited access to intravenous cocaine hydrochloride or heroin hydrochloride. Animals self-administering cocaine quickly developed a pattern of episodic drug intake, with periods of excessive cocaine self administration alternating with brief periods of abstinence. Subjects allowed continuous access to intravenous heroin showed stable drug self-administration, with a gradual increase in daily heroin intake over the first two weeks of testing. The general health of the animals became markedly different: those self administering heroin maintained grooming behavior, pretesting body weight, and a good state of general health; rats self-administering cocaine tended to cease grooming behavior, to lose up to 47% of their pretesting body weight, and to show a pronounced deterioration in general health. The mortality rate for 30 days of continuous testing was 36% for animals self-administering heroin and 90% for those self-administering cocaine. These results suggest that cocaine is a much more toxic compound than heroin when animals are given unlimited access to intravenous drug. PMID- 4039768 TI - [Fibrinolytic activity in cutaneous lesions of hereditary hemorrhagic telangiectasia]. PMID- 4039769 TI - [Analysis of the papillary muscle image on thallium-201 myocardial scintigram in various heart diseases]. PMID- 4039770 TI - [Echo- and electrocardiographic signs of different forms of hypertrophic cardiomyopathy]. AB - Twenty-six patients with idiopathic and secondary hypertrophic cardiomyopathies were examined. The diagnostic value of echo- and electrocardiographic signs of hypertrophic cardiomyopathy is discussed, the more important among those being the thickness and shape of the interventricular septum, anterosystolic movement of the anterior cusp of the mitral valve, electrocardiographic evidence of left ventricular hypertrophy and left-atrial changes, abnormal Q waves. PMID- 4039771 TI - [Effect of laser therapy in diabetic retinopathy on the hemodynamics of retinal vessels]. AB - Changes in retinal hemodynamics are a factor of major influence in diabetic retinopathy. With the aid of videoangiography, the changes in retinal circulation times before and after therapeutic laser coagulation were examined in a prospective study. A marked diminution of all circulation times was observed after laser coagulation procedures: the arterial circulation time decreased from 1.02 s to 0.74 s average, the early venous circulation time from 5.18 s to 3.50 s average, and the late venous circulation time from 9.07 s to 8.16 s. Laser coagulation has a more significant influence on the capillary circulation of the retina than on the venous phase. In diabetic retinopathy, the improvement in pathologic hemodynamic situations in the retina may be a very important mechanism of action in laser coagulation therapy. PMID- 4039772 TI - [Initial experiences in the treatment of changes in the anterior eye segment with the neodymium:YAG laser]. AB - The present paper reports the first results with the Meditec OPL-3 neodymium:YAG laser (Rodenstock, Munich). The YAG laser is a pulsed laser, the biological effects of which are based on the formation of plasma at its focal point. Plasma formation induces a rapid explosion-like expansion of the tissue. This effect can be used to sever opaque structures of the refractive media of the eye, such as secondary cataracts, membranes or strands. The paper summarizes the results of the first 80 consecutive cases treated with the laser. The surgical procedure is described in detail. Visual acuity improved instantaneously in all cases in which no concomitant eye pathology (e.g., corneal or macular changes) existed. Complications consisted in the development of postoperative inflammatory reactions and increases in intraocular pressure, and responded well to corticosteroids and beta-blockers or Diamox. The development of the neodymium:YAG laser has considerably advanced our therapeutic possibilities. PMID- 4039773 TI - [Aqueous humor outflow capacity after argon laser trabeculoplasty. Preliminary report]. AB - In a prospective study of 44 eyes with open angle-glaucoma and 27 with pseudocapsular glaucoma, the aqueous humor outflow facility was controlled for up to 12 months following argon laser trabeculoplasty (ALT). The average increase in the facility of outflow, which was 70% in open-angle glaucoma, was 25% higher in pseudocapsular glaucoma. In successful ALT, this increase in outflow facility was established within the first 20 hours after coagulation and did not decrease during the following year. There were no major complications such as transitory elevations of intraocular pressure, hyphema, or severe uveitis; this fact is interpreted as a result of the authors' technique, in which only the light pigmented trabecular meshwork is coagulated. PMID- 4039774 TI - [Histologic studies on the effect of light coagulation of the retina on the vitreous body]. AB - Up to 6 months after panretinal photocoagulation of rabbit eyes the subsequent changes in the vitreous body were examined histologically by means of a stereomicroscope. Marked changes were evident: severe exudation into all of the vitreous tissue during the early follow-up period, circumscribed areas of higher density or loss of normal density, membrane-like structures, confluent cavities and liquefaction of most of the tissue at the later postcoagulative stage. PMID- 4039775 TI - [Benefit and risk of high-dose metoclopramide in comparison to high-dose haloperidol or triflupromazine in cisplatin-induced vomiting]. AB - The antiemetic efficacy of metoclopramide (MCL, Paspertin, loading infusion 0.5 mg/kg body wt./h over 2 h, maintenance infusion 0.25 mg/kg/h over 24 h) has been compared with haloperidol (HAL, Haldol, 1/10 of MCL dosage) and with triflupromazine (TFP, Psyquil, 1/2 of MCL dosage) in two sequential analyses, against the emetic effects of cisplatin (60-90 mg/m2). After treating 14 and 8 pairs of patients respectively, MCL was significantly (alpha = 0.05) more effective than HAL or TFP. Only 1 of the 14 patients in the HAL group and 0 of 8 in the TFP group were totally protected against emesis, in contrast to 6 of 14 patients and 3 of 8 in the MCL groups. In order to quantify the benefit/risk relationship of the antiemetic drugs studied the number of prevented emetic episodes (in comparison to previous insufficient treatment) was related to the incidence of major undesired effects (i.e. dystonia and/or akathisia). This relationship was 17.8 and 12.1 for the two MCL groups; for HAL and TFP it was only 5.8 and 4.6, respectively. The high antiemetic selectivity of MCL against cisplatin-induced emesis is probably related to the still unknown action of MCL on the gastrointestinal motility. A high neuroleptic potency, with or without additional anticholinergic activity, is apparently not essential for high antiemetic protection against cisplatin. PMID- 4039776 TI - How salt causes hypertension: the natriuretic hormone-Na/Ca exchange- hypertension hypothesis. AB - The hypothesis outlined below shows how an underlying functional (genetic or acquired) defect in renal excretion (undetectable by standard renal function tests) can, in the presence of an excessive salt load, lead to the development of hypertension. The initial tendency toward salt and water retention and extracellular fluid volume expansion is compensated by the secretion of a natriuretic hormone that promotes Na excretion by inhibiting Na pumps in renal tubule cells. The hormone also inhibits Na pumps in other types of cells, however, including vascular smooth muscle cells, so that the intracellular Na concentration rises in these cells. Then, because the vascular smooth muscle cells contain a Na/Ca exchange transport system in their plasma membranes, more Ca than normal will be delivered to these cells. This will cause the increased contractility and reactivity that underlies increased vascular tone and peripheral vascular resistance which is the direct cause of the elevated blood pressure. PMID- 4039777 TI - Humoral factors in the pathogenesis of primary hypertension. AB - In 42 spontaneously hypertensive rats of the Munster strain either parabiosis or cross circulation with normotensive Wistar Kyoto rats was performed. Cross circulation was made through the common carotid arteries and external jugular veins using a peristaltic pump. In parabiosis and in cross circulation experiments hypertension was transmitted from the spontaneously hypertensive rats to normotensive rats. Nephrectomy or adrenalectomy in the spontaneously hypertensive rat before cross circulation abolished this effect. After volume depletion in the hypertensive animals hypertension was not transmitted either. It is concluded that humoral factors causing vasoconstriction play an essential role in the development of hypertension in the spontaneously hypertensive rat. PMID- 4039778 TI - Atrial natriuretic factor: isolation, identification, biological and pharmacological actions. PMID- 4039779 TI - Effects of concurrent pregnancy and lactation on reproduction in four strains of mice. AB - The influence of concurrent pregnancy until the third lactation on reproduction was studied in four strains of mice (SHN, SLN, C3H/He and GRS/A) as a possible step to evaluate the efficiency of this system on offspring production. In all strains, little difference was observed between sequential and concurrent pregnancy and lactation groups in any parameter as the index of reproductivity- delivery interval, litter size, average weight and growth rate of pups, mother weight, rearing rate, still-birth rate and rate of still-born pups. Also, no difference was seen between groups of any strain, in the number of females which had three litters. The estimated number of pups weaned per female during 50 days after first being placed with males was higher in the concurrent pregnancy groups than in the sequential pregnancy groups of all strains. Meanwhile, the incidence of spontaneous mammary tumors, the major characteristic of these strains, was consistently lower in the concurrent pregnancy group in all strains. These results have demonstrated that the concurrent pregnancy and lactation system is an efficient means of mouse production. PMID- 4039780 TI - Discussion on the state of water in the myofilament lattice and other biological systems, based on the fact that the usual concepts of colloid stability can not explain the stability of the myofilament lattice. AB - Application of the usual concepts of colloid stability shows that the in vivo spacings between the myofilaments, making up the contractile part of the muscle myofibrils, correspond to energies of 10(-4) to 10(-1) kT. Refinements in the calculations of the electrostatic and Van der Waals-London energies do not significantly modify these values. Therefore, theory does not predict the observed stability of the myofilament lattice. It is shown that the interfilament water very likely plays an active role in the myofilament lattice. More generally, the structure of water in living cells is probably different from that of bulk water. PMID- 4039781 TI - Three-dimensional cardiac anatomy and function in heart disease in adults: initial results with the dynamic spatial reconstructor. AB - The dynamic spatial reconstructor, or DSR, is a unique high-speed volume-imaging x-ray scanner based on computed tomographic principles. In this report, we present data obtained from the first feasibility DSR studies of adult patients with heart disease. Information from three patients--one with hypertrophic obstructive cardiomyopathy, one with calcific aortic valvular disease, and one with a left ventricular aneurysm--is described in detail. The mean DSR scanning time for each patient was 20 seconds, and the mean total irradiation to the sternum was 15.3 R. Transverse cross sections were reconstructed and then retrospectively reformatted to provide operator-selected oblique sections in space (for example, long-axis and short-axis sections of the left ventricle), to follow these sections through time (such as from end-diastole through end systole), and to create three-dimensional displays (for instance, of the left ventricular chamber). Unique quantitative measurements of structure and function were made by using these images. For generation of most imaging data, only one injection of contrast material into the right side of the heart is necessary. Clinically useful three-dimensional dynamic imaging data can be acquired from adult patients with heart disease by using the DSR. Compared with conventional angiocardiography, DSR studies can provide information with less x-ray exposure and fewer angiographic injections. PMID- 4039782 TI - Cholinergic agents: antinociception without morphine type dependence in rats. AB - We have confirmed the work of others showing that loss in body weight is a predictable and consistent sign of opiate withdrawal in rats. Rats that were treated chronically with either oxotremorine or physostigmine displayed no weight loss or other signs of opiate-like withdrawal when the drugs were withdrawn. Furthermore, there was no difference in weight loss between morphine dependent rats substituted with saline and those substituted with either cholinergic drug. However, we did observe an increased mortality among rats substituted with a cholinergic agent compared with saline. Rats infused with a mixture of morphine plus oxotremorine or morphine plus physostigmine showed less weight loss, but not fewer behavioral signs, after the end of the infusion than rats treated only with morphine. It is concluded that the cholinergic agents did not cause a morphine like physical dependence themselves, but appeared to antagonize to some extent the development or manifestation of opiate dependence. PMID- 4039783 TI - Free fatty acid content of human milk: physiologic significance and artifactual determinants. AB - Analysis of human milk was conducted to determine if free fatty acids occur naturally or as a consequence of artifactual lipolysis after milk expression. Five mothers provided triplicate early morning milk samples on day 43 of lactation. Following extraction, lipid classes were separated by preparative thin layer chromatography and quantified by capillary gas liquid chromatography. Fresh milk samples collected with 20 volumes chloroform-methanol (1:1, v/v) were analogous in total free fatty acid level and profile of fatty acids to a duplicate sample collected with 0.4M EDTA and immediately frozen at -10 C. Low milk levels of free fatty acids appear to exist naturally. During days 4-37 of lactation, four serial milk samples from 15 mothers were collected and frozen with 0.4M EDTA. The concentration of free fatty acids in colostrum (0.03-0.5%, w/w) was lower than for subsequent days (0.3-2.5%, w/w). Additional samples were collected with and without a lipase inhibitor (0.4M EDTA) and subjected to routine collection and storage procedures. Significantly different fatty acid profile and higher levels of free fatty acids in milk collected without a lipase inhibitor added indicate that domestic freezing and/or thawing ruptures the fat globule membrane, allowing sn-1-stereospecific serum stimulated lipoprotein lipase contact with its triglyceride substrate. Standard procedures for collection of human milk for gavage fed infants appears to stimulate artifactual lipolysis of milk triglyceride and subsequent release of free fatty acids. The proposed relationship between dietary free fatty acids and prolonged, unconjugated hyperbilirubinemia in the newborn is discussed with regard to the significance of preintestinal lipolysis. PMID- 4039784 TI - Sexual dysfunction in men with alcoholic liver cirrhosis. A comparative study. AB - Sexual dysfunction in men with alcoholic cirrhosis was investigated in young (less than 56 years) outpatients with steady female partners. Sixty-one per cent (11/18) claimed sexual dysfunction, with erectile dysfunction and/or reduced sexual desire being the most common symptoms. Comparing patients with (n = 11) and without (n = 7) sexual dysfunction, no significant differences were found concerning a number of pertinent clinical variables. This should be interpreted with caution, however, owing to the small number of patients in each group. The prevalence and type of sexual dysfunction were not significantly different comparing alcoholic cirrhotic men to chronic alcoholic men without overt liver disease (matched for duration of alcoholism, age and duration of partnership) and to insulin-dependent diabetic men (matched for age and duration of partnership). However, all groups had a significantly (p less than 0.025) raised prevalence of sexual dysfunction when compared to men without chronic disease (matched for age and duration of partnership). PMID- 4039785 TI - [Pharmacokinetics of the antitumor drug oxoplatinum labeled with 191Pt]. AB - A pharmacokinetic study of the antitumor drug oxoplatinum labeled with 191Pt when administered to control mice and mice with B-16 melanoma have shown that distribution of the drug in organs and tissues in both groups of animals is nonuniform. The drug is more tropic to the kidneys, liver, spleen, adrenals, thymus, skin and tumor. Correlation was established between the values of the coefficient ratios of differential accumulation (CDA) of the organ/blood in the final and initial periods of observation and the period of the drug half-life in the organs. The higher the CDA of the organ/blood the longer the period of the drug half-life. The excretion of the drug from the blood and most other organs is described by a bioexponential curve. PMID- 4039786 TI - Cerebellar neurofilaments, neonatal copper deficiency and epilepsy. PMID- 4039787 TI - Is the terminal degradation of neurofilaments regulated by mitochondrial production of oxygen radicals? PMID- 4039788 TI - Site-specific DNA binding of nuclear factor I: analyses of cellular binding sites. AB - Nuclear factor I is a cellular site-specific DNA-binding protein required for the efficient in vitro replication of adenovirus DNA. We have characterized human DNA sequences to which nuclear factor I binds. Three nuclear factor I binding sites (FIB sites), isolated from HeLa cell DNA, each contain the sequence TGG(N)6 7GCCAA. Comparison with other known and putative FIB sites suggests that this sequence is important for the binding of nuclear factor I. Nuclear factor I protects a 25- to 30-base-pair region surrounding this sequence from digestion by DNase I. Methylation protection studies suggest that nuclear factor I interacts with guanine residues within the TGG(N)6-7GCCAA consensus sequence. One binding site (FIB-2) contained a restriction endonuclease HaeIII cleavage site (GGCC) at the 5' end of the GCCAA motif. Digestion of FIB-2 with HaeIII abolished the binding of nuclear factor I. Southern blot analyses indicate that the cellular FIB sites described here are present within single-copy DNA in the HeLa cell genome. PMID- 4039789 TI - Protection and potentiation of radiation clastogenesis by caffeine: nature of possible initial events. AB - Data on the differential modification of the oxic and anoxic components of radiation clastogenesis by caffeine already published in the literature have been briefly reviewed, additional unpublished data relevant for consideration of possible mechanisms have been presented and the possible events in terms of radiation chemistry have been discussed. It is considered that radioprotection against oxic component possibly results from the competition of caffeine with oxygen for e-aq, whereas radiosensitization of the anoxic component is, at least partly, due to restoration of physico-chemical environment achieved by oxygen alone in the irradiated cells. These reactions involve eaq-, oOH and H2O2 formed in the cells exposed to ionizing radiation. PMID- 4039790 TI - Towards a more comprehensive evaluation of a genotoxic hazard in man. PMID- 4039791 TI - cis-Dichlorodiammine platinum(II) induced aberrations in mouse bone-marrow chromosomes. AB - The clastogenic effect of cis-dichlorodiammine platinum(II) (cis-platin) on mouse bone-marrow chromosomes has been studied. Cis-platin was injected at 3 different doses. Cells were fixed at different time intervals after treatment. Different types of aberrations together with the percent of mitotic index and frequency of abnormal metaphases were studied. The aberrations observed were primarily chromatid breaks, although isochromatid breaks, interchanges, and multiple breaks were also observed. A dose- and time-dependent effect was observed for both inhibition of mitotic index and frequency of abnormal metaphases. Trypsin-Giemsa staining of bone-marrow metaphase chromosomes from normal mice was compared with the bands of metaphase chromosomes obtained after Giemsa staining of chromosomes from platinum-treated mice and they were observed to be identical. Bands were present up to 120 h and aberrations were also induced in such plates. PMID- 4039792 TI - Consequences of unremitting middle-ear disease in early life. Otologic, audiologic, and developmental findings in children with cleft palate. AB - To learn whether chronic otitis media with effusion during early life has lasting otologic, audiologic, or developmental consequences, we evaluated 24 closely matched pairs of children with repaired palatal clefts whose treatment had been equivalent except with regard to persistent otitis media during early life. One group had undergone early (mean age, 3.0 months) myringotomy with placement of tympanostomy tubes, followed by assiduous monitoring and an aggressive treatment program to maintain ventilation in the middle ear. The other group had undergone initial myringotomy later (mean age, 30.8 months) or not at all (two subjects) and presumably had had continuous middle-ear effusion throughout most or all of the first few years of life. Eardrum scarring was equal in both groups. Hearing acuity and consonant articulation were impaired in both groups, but hearing acuity was less impaired (P = 0.05 to 0.10) and consonant articulation significantly less impaired (P = 0.03) in the group undergoing early myringotomy. Mean verbal, performance, and full-scale IQs and scores on psychosocial indexes were normal in both groups and did not differ significantly between the groups. These findings support the hypothesis that early, longstanding otitis media may result in impairment of hearing and of speech, but they do not support the hypothesis that cognitive, language, and psychosocial development are adversely affected. PMID- 4039793 TI - Fatal eosinophilic meningoencephalitis and visceral larva migrans caused by the raccoon ascarid Baylisascaris procyonis. PMID- 4039794 TI - Tissue responses against Cladosporium trichoides and its parasitic forms in congenitally athymic nude mice and their heterozygous littermates. AB - The tissue responses against Cladosporium trichoides and its parasitic forms were studied using nude (nu/nu) mice and their heterozygous (nu/+) littermates of BALB/c background. 1.0, 0.1 and 0.01% cell suspensions were prepared from a culture broth which had been inoculated with the C. trichoides and cultured with reciprocal shaking at 27 degrees C for 7 days. Sixty nu/nu or 60 nu/+ mice were divided into three groups consisting of 20 each which was allotted to one of the three cell suspensions. Each mouse was inoculated intravenously with 0.1 ml of either the cell suspensions. Two mice from each of the six groups were sacrificed at adequate intervals until 30 days after inoculation and histopathologic sections stained with H & E or by PAS were prepared from their visceral organs. There were no characteristic findings in the nu/nu and nu/+ mice inoculated with the 0.01% cell suspension. When inoculated with the 1.0% cell suspension, the brain was the favorite target organ in both groups of mice and the kidney was the second. When inoculated with the 0.1% cell suspension, brain lesions were observed only in the nu/nu mice. The susceptibility of the nu/nu mice was higher than that of the nu/+ mice. The parasitic forms in the brain of the nu/nu and nu/+ mice were slender septate true hyphae with or without polymorphonuclear leucocyte infiltrate, while in the liver, spleen and lung of both groups of mice the parasitic forms were short thick hyphae, moniliform hyphae, chlamydospores or round cells (sclerotic cells). Many giant cells containing fungal elements appeared in the liver of the nu/nu mice. PMID- 4039796 TI - Effect of cis-diamminedichloroplatinum (II), cyclophosphamide and tumor age on the rate of mitochondrial and overall cellular protein synthesis in Zajdela hepatoma. AB - The effect of in vivo treatment with cis-Pt(II) and/or cyclophosphamide on overall cellular and mitochondrial protein synthesis in Zajdela hepatoma was examined. The rate of the overall cellular protein synthesis decreased by about 60-80%, whereas the rate of the process in mitochondria was affected only marginally upon the treatment. Qualitatively similar changes in the relative rates of the two processes were found in Zajdela hepatoma cells during the ageing of the tumor. PMID- 4039795 TI - Antifungal therapy of dermatophytosis in guinea pigs and congenitally athymic rats. AB - Guinea pigs and athymic nude (RNU/RNU) rats were used to assess the efficacy of three orally administered antifungal agents--Tolciclate, Tolnaftate, and Ketoconazole--against Trichophyton mentagrophytes dermatophytosis. All three antifungal agents inhibited the test strain of T. mentagrophytes in vitro. Antifungal agents were tested in intervention (oral therapy started 5 days after challenge) or prophylaxis (oral therapy started 5 days before challenge) protocols. Oral treatment of dermatophytosis on guinea pig skin demonstrated that Tolciclate and Tolnaftate alleviated clinical symptoms and shortened the duration of the dermatophytosis, in comparison to nontreated controls. Assessment of antifungal efficacy in the guinea pig model was time consuming (30-35 days) and variability in the duration and severity of clinical symptoms on guinea pig skin was common. Oral therapy of chronically infected athymic rats demonstrated that Tolciclate, Tolnaftate, and ketoconazole were effective antifungal agents in vivo. Obvious improvement in clinical symptoms of dermatophytosis (i.e. less erythema and fewer lesions) was evident with all three antifungal agents within 10 days of starting oral therapy. By day 20, athymic rats that were treated with either Tolciclate or Ketoconazole showed marked clinical improvement of the chronic dermatophytosis. Chronically infected athymic rats, which lack thymus matured T-cells, are a promising new model to evaluate the efficacy of antifungal agents by culture, histology, and visual observations of clinical symptoms. PMID- 4039797 TI - Ototoxicity of cis-diamminedichloroplatinum. AB - In 19 evaluable cancer patients treated with cis-diamminedichloroplatinum (cis DDP) Platidiam-Lachema containing chemotherapy the ototoxicity was assessed. There was an increase of hearing threshold of air-conduction in frequency of 6000 and 8000 Hz as compared with pretreatment audiograms in four patients (21%). In one case only the hearing loss was reversible. The usual hearing loss was of 10- 15 dB and maximal of 20 dB. In those four patients with ototoxicity the decrease of creatinine clearence under 60 ml/min occurred at the same time. It is suggested that the altered renal function could be a cause of cis-DDP level rise in body liquids and in this way a cause of further more severe side effects. Neither subjective hearing loss nor tinnitus nor otalgia was found. The cis-DDP caused high frequency hearing loss but has not affected the correct speech percept. To avoid serious cis-DDP ototoxicity it is necessary to monitor renal functions and audiograms carefully and to administer cis-DDP slowly in chloride containing vehicles after sufficient prehydratation. PMID- 4039798 TI - Chemotherapy and/or removal of the peritoneal catheter in the management of fungal peritonitis complicating CAPD? PMID- 4039799 TI - Effect of gestational and neonatal styrene exposure on dopamine receptors. AB - The effect of styrene (200 mg/kg, orally) on dopamine receptor binding using 3H spiroperidol as a specific ligand was studied in developing rats. Gestational exposure caused no significant change in the binding of 3H-spiroperidol to striatal membranes of pups at 2 and 3 weeks of age. However, styrene exposure during lactation and the gestation-lactation period caused a significant increase in binding of 3H-spiroperidol. Scatchard analysis revealed that styrene exposure caused an increase in the number of receptor sites without affecting their affinity. Results of behavioral studies (amphetamine-induced locomotor activity and apomorphine-induced stereotypy) showed that styrene exposure during the gestation-lactation period caused a significant increase in motor activity and stereotypy of the rat pups. These behavioral and biochemical studies suggest that early postnatal exposure to styrene affects dopaminergic function. PMID- 4039800 TI - Exploratory studies of a rodent model for inhalant abuse. AB - For simulation of inhalant abuse exposure conditions, male and female rats were exposed to high concentrations (10,000-30,000 ppm) toluene vapor until unconscious (8-12 min periods). Sex differences were observed in the mean times to onset of sleep during exposure; linear regression lines of min to sleep onset as a function of toluene/kg body wt had slopes of -0.7492 for males and -0.4515 for females. Animals were removed from the exposure chamber to clean air and both spontaneous horizontal locomotor activity (2/3 animals) and ppm toluene in exhaled air (1/3 animals) were monitored for the first hr post-exposure. Animals regained consciousness within the first 6-7 min and consistently displayed a characteristic pattern of locomotor activity: activity increased initially to 2-3 times baseline level (1 hr preceding exposure) and remained elevated for approximately 10 min; activity then decreased to baseline range for a time before a period of inactivity and/or sleep by 60 min post-exposure. Immediately after regaining consciousness the concentration of toluene exhaled decreased rapidly for the first 10 min, somewhat less rapidly for the next 10-20 min and levelled off at 100-200 ppm for the following 30-40 min. The occurrence and duration of hyperactivity coincided with the period of rapid elimination of unchanged toluene through the lungs. PMID- 4039802 TI - Effects of naloxone and other opiate antagonists on blood-ethanol concentration in acutely-ethanol-intoxicated rats. AB - The effects of naloxone hydrochloride (NAL) and other opiate antagonists on blood ethanol concentration (BEC) in acutely-ethanol-intoxicated rats were examined. Using a 1 mg/kg body wt. dose of NAL, the maximum decrease in BEC was found to occur at 30 min. At 30 min after administration of various doses of NAL, it was found that BEC was decreased maximally by a 2 mg/kg dose, whereas the first significant decrease was caused by a 10 micrograms/kg dose. BEC was also decreased by naltrexone (1 mg/kg), but not by a 4 mg/kg dose of any of four Mr compounds (Mr 1452, Mr 1453, Mr 2266 and Mr 2267). It is suggested that pharmacokinetic antagonism of acute alcohol intoxication by naloxone and naltrexone is unrelated to the property of opiate antagonism, but may involve the ability of certain such antagonists to interact with hepatic NAD+-dependent oxidative metabolism. PMID- 4039801 TI - Effects of antidepressant drugs on a quickly-learned conditioned-suppression response in mice. AB - Mice experienced to electric shock, exhibited a marked suppression of motor activity when placed in the same cage 24 hr after administration of shocks. Acute administration of imipramine-HCl (10 mg/kg, i.p.), desipramine-HCl (5 and 10 mg/kg, i.p.) and amitriptyline-HCl (5 and 10 mg/kg, i.p.) caused marked reduction of the conditioned suppression of shocked mice, but reduced the motor activity of the non-shocked mice. Maprotiline, mianserin and dimetacrine did not cause reduction of the conditioned suppression. Nialamide (100 mg/kg, i.p.) and pargyline-HCl (100 and 200 mg/kg, i.p.) caused marked reduction of the conditioned suppression but did not increase the motor activity of the non shocked mice, and tranylcypromine-HCl (10 and 20 mg/kg, i.p.) did not cause reduction of the conditioned suppression. Diphenhydramine-HCl (10 and 20 mg/kg, i.p.) reduced the conditioned suppression of shocked mice in a dose-related manner. Chronic administration of imipramine-HCl (1 and 5 mg/kg, i.p.) for 14 days significantly reduced the conditioned suppression but did not influence the motility rate of the non-shocked mice. Also, chronic administration of amitriptyline (1 mg/kg, i.p.), desipramine (5 mg/kg, i.p.) and dimetacrine (10 mg/kg, i.p.), for 10 days, significantly reduced the conditioned suppression, but did not influence the motility rate of the non-shocked mice. Chronic administration of maprotiline reduced the conditioned suppression. On the other hand, chronic administration of mianserin (5 mg/kg, i.p.) and diphenhydramine (10 mg/kg, i.p.) did not cause a reduction of the conditioned suppression. PMID- 4039803 TI - Spinal vascular tumors: dilemmas in diagnosis and management. AB - Three case reports of spinal vascular tumors illustrate the need for well organized and thorough neuroradiological and neurosurgical planning to achieve an initial cure without delay and to avoid inadequate operative procedures. PMID- 4039804 TI - Simulation of a prolactin-secreting adenoma by an intrasellar craniopharyngioma. AB - We report here an unusual case of a 21-year-old woman who presented with amenorrhea, galactorrhea, and hyperprolactinemia (66 to 81 ng/ml) secondary to an unsuspected intrasellar craniopharyngioma. The results of preoperative endocrine testing were compatible with the presence of a prolactin-secreting adenoma. Moreover, high resolution computed tomographic scanning revealed an uncalcified hypodense sellar mass that did not enhance after contrast administration, a feature shared by many prolactinomas. This report illustrates that amenorrhea, galactorrhea, mild to moderate hyperprolactinemia, and a sellar mass should not automatically be attributed to the presence of a prolactin-secreting adenoma. PMID- 4039805 TI - Failure of postictal growth hormone rise in a patient with thalamic lesions. AB - A patient with bilateral thalamic lesions had a spontaneous generalized convulsion during nocturnal polygraphic recording. Postictal measurements of cortisol and prolactin showed the expected rise of plasma values at 30 and 60 minutes after the seizure, but growth hormone did not increase. This observation suggests that suprahypothalamic mechanisms regulating growth hormone release differ from those involved in the neural control of cortisol-ACTH and prolactin secretion. The thalamus may intervene as a regulatory center in the release of growth hormone. PMID- 4039806 TI - Inhibition of flank-marking behavior in golden hamsters by microinjection of a vasopressin antagonist into the hypothalamus. AB - Microinjection of arginine-vasopressin (AVP) into the medial preoptic area of the hypothalamus of the hamster stimulates flank marking, a complex stereotypic motor behavior involved in olfactory communication. Microinjection of an antagonist of AVP, [1-deaminopenicillamine-2-(O-methyl)-tyrosine]arginine-vasopressin, into the same site blocks both the effect of microinjected AVP as well as the natural flank-marking behavior normally elicited by placing a hamster into the recently vacated home cage of another hamster. This finding supports the notion that AVP is a transmitter in the expression of flank marking. PMID- 4039807 TI - Cystic disease of the liver studied by 99Tcm DISIDA and 99Tcm sulphur colloid imaging. AB - Two patients with cystic disease of the liver have been studied with 99Tcm sulphur colloid and 99Tcm DISIDA scintigraphy and CT. One patient's cystic lesions are substantially enlarged as seen in 99Tcm sulphur colloid scintigrams performed at 10 year intervals. Another patient's scintigraphic studies performed at 5 year intervals demonstrated no significant progression in the size of the cysts in the liver. The 99Tcm DISIDA scintigram of each patient demonstrated no radiotracer filled-in in the cystic lesions (photon deficient areas on 99Tcm sulphur colloid scan). This finding may be used to differentiate cystic disease of the liver from hepatoma, in which usually DISIDA filled-in the defects seen on the 99Tcm sulphur colloid scintigram. PMID- 4039808 TI - Hereditary antithrombin III deficiency and pregnancy: report of two cases and review of the literature. AB - The pregnancy and the serum antithrombin III levels during the antenatal and postpartum period of two patients with hereditary antithrombin III deficiency is described. Both antithrombin III antigen and activity levels dropped to their lowest levels immediately after delivery. A review of the literature emphasizes the high risk for thromboembolism in patients with hereditary antithrombin III deficiency. Important considerations for the obstetrician concerning hereditary antithrombin III deficiency are discussed, including: 1) the need to therapeutically anticoagulate these patients postpartum, 2) the need to consider prophylactic anticoagulation throughout pregnancy especially in patients with a history of thrombosis, 3) the practical aspects of assaying antithrombin III in plasma rather than serum, 4) the normally low antithrombin III levels in normal newborns, and 5) the need to provide prepregnancy counseling, including information about the autosomal dominant inheritance of hereditary antithrombin III deficiency. PMID- 4039809 TI - Transscleral cyclocoagulation using a neodymium:YAG laser. AB - A series of pigmented rabbit eyes were treated with pulsed 10 msec (free running mode) neodymium:YAG laser burns to achieve transscleral cyclocoagulation. Grossly evident burns were created in the ciliary body with laser pulses of 1.5 joules of energy. Sustained reduction in intraocular pressure was obtained when 30 such laser burns were made in an eye. PMID- 4039810 TI - Retinal pigment epithelial dysfunction in early ovine ceroid lipofuscinosis: electrophysiologic and pathologic correlates. AB - Retinal degeneration is a major finding in the human and ovine ceroid lipofuscinosis. Sequential electroretinographic (ERG) studies in a young, asymptomatic, affected lamb are presented here, which demonstrate a progressive loss of the scotopic b-wave and unrecordable c-waves under halothane anesthesia. Even at this initial stage of disease, lesions were evident in the form of dystrophic retinal pigment epithelial (RPE) villi, and loss of photoreceptor cells and rod outer segments. Cone inner segments were enlarged and scanning electron microscopy emphasized these abnormalities. All cells in tapetal and nontapetal areas contained fluorescent inclusions with similar emission spectra (maximum = 539 nm). By transmission electron microscopy, storage bodies consisted of 'finger-print' profiles and were most prominent in bipolar cells. The pathological features of the retina correlate well with the observed ERG changes, reaffirming the sheep as a useful model to delineate early events in ceroid lipofuscinosis. PMID- 4039811 TI - Trichosporon beigelii: survey of isolates from clinical material. AB - Two hundred and eight isolates of Trichosporon beigelii were identified over the period January 1973 to July 1983. 45.7% of these were from skin, 25.0% from nail, 22.6% from tissues and fluids, 3.4% from hair and 3.4% from sputum. Tr. beigelii was isolated in association with a recognized pathogen in 23 cases, 9 with a yeast, 14 with a dermatophyte. In 38 cases, Tr. beigelii was the only organism isolated when direct microscopic examination of clinical material showed the presence of hyphae and/or yeast cells. Although Tr. beigelii could only be assigned a definite pathogenic role in 6 cases of genital white piedra, and in one case of peritonitis associated with chronic ambulatory peritoneal dialysis, we believe that this organism was pathogenic in many cases of skin infection. In most of the cases where it was isolated from tissue or fluids at Royal North Shore Hospital, Tr. beigelii was not considered to be significantly contributing to the disease process. PMID- 4039812 TI - [Regional circulatory changes after massive blood loss in immobilization stress]. PMID- 4039813 TI - [Effect of different stressors on adrenergic mechanisms and cholinoreception in guinea pigs]. PMID- 4039814 TI - [Course of the early neonatal period of high birth-weight infants]. PMID- 4039815 TI - Recognition of a cytosine base lesion by a human damage-specific DNA binding protein. AB - Sodium bisulfite reacts with cytosine and 5-methylcytosine, forming the 5,6 dihydrosulfonate adducts which deaminate to the uracil and thymine adducts, respectively. At alkaline pH, the sulfonate groups are then released, generating uracil and thymine. In DNA, the resulting G:U and G:T base mismatches generated are potential sites of mutagenesis. Using a human damage-specific DNA binding protein as a probe, we have found protein-recognizable lesions in bisulfite treated DNA and poly d(I-C), but not in treated poly d(A-T) or poly d(A-U). Although this suggests that the lesion recognized is cytosine-derived, there was no correlation between the number of uracils induced and the number of binding sites, suggesting that the protein-bound damage is not a uracil-containing mismatch. Modification of the treatment protocol to reduce elimination of the bisulfite from the base adducts increased the level of binding, suggesting that the protein recognizes a base-sulfonate adduct. PMID- 4039817 TI - Unwinding of supercoiled DNA by cis- and trans-diamminedichloroplatinum(II): influence of the torsional strain on DNA unwinding. AB - The effective unwinding angle, phi, for cis-diamminedichloroplatinum(II) (cis DDP) and trans-DDP was determined by utilizing high resolution gel electrophoresis and supercoiled phi X174 RF DNA as a substrate. The effective unwinding angle was calculated by equating the reduction in mobility of the DDP modified DNA to the removal of a number of superhelical turns. The value of the effective unwinding angle for both DDP isomers was greatest at the low levels of DDP bound and decreased with increasing amounts of unwinding agent. The cis isomer is a better unwinding agent than is the trans-isomer, being nearly twice as effective in unwinding the supercoiled DNA at the DDP levels investigated. A comparison of the magnitude of phi below rb values of 0.005 and those at high levels of binding reveals that the extent of torsional strain in the supercoiled DNA influences the magnitude of the unwinding of the DNA by these complexes. When this method is used in the analysis of the unwinding angle for a covalently bound species on supercoiled DNA, it may provide a more reliable estimate of the magnitude of phi at high degrees of supercoiling and at low levels of modification. PMID- 4039816 TI - Characterization of a mitochondrial protein binding to single-stranded DNA. AB - A DNA-binding protein from Xenopus laevis oocyte mitochondria which has been found associated with the D-loop also shows a strong preference for single stranded DNA. The binding to polynucleotides is dependent on the base composition, but no sequence specificity was found. This protein, called mtSSB, binds tightly and cooperatively to single-stranded DNA. By its amino-acid composition and its binding properties it appears to be similar to the single stranded DNA-binding proteins found in prokaryotes. PMID- 4039818 TI - [Nuclear medicine demonstration of esophageal bile reflux]. AB - Biliary and pancreatic juice has been implicated as a cause of regional inflammation or carcinoma after gastric surgery. We studied 38 patients after gastrectomy using a modification of cholescintigraphy (185 mBq 99m-Tc-DESIDA i.v.). As soon as the tracer had reached the duodenum, a dynamic study (30 min, 120 frames) was started. Thereafter a static image of the epigastrium and thorax in the anterior view with more than 1000 cts/cm2 was recorded. This procedure was repeated after a meal. Of 29 patients without complaints only 4 had a reflux into the jejunal loop. By contrast in 7 of 9 patients with suggestive symptoms this examination demonstrated bile reflux which reached the oesophagus in 6 cases. A stenosis of the distal oesophagus prevented oesophageal reflux in one patient. 2 patients with oesophageal reflux had a history of oesophageal stenosis and oesophagitis confirmed by endoscopy. The remaining 2 patients without demonstrable reflux had neither oesophagitis nor radiologically verified reflux. Cholescintigraphy as modified by us may detect clinical relevant bile reflux into the oesophagus. This is important for surgeons selecting patients with potential benefit from a reoperation. Since most patients with complaints after gastrectomy have had demonstrable bile reflux, reflux-reducing surgical techniques should be used in all. PMID- 4039819 TI - Anterior uveitis associated with Kawasaki syndrome. AB - Forty-one children with a clinical diagnosis of Kawasaki syndrome had a pediatric ophthalmologic examination performed at a mean time of 8.6 days after onset of fever. Twenty-seven of 41 patients (66%) had evidence of anterior uveitis by slit lamp examination. Bilateral involvement was noted in 25 of 27 patients (97%). Punctate keratitis was evident in 5 of 41 patients (12%). Three of these five had coexisting uveitis. The incidence of anterior uveitis in patients examined during the first week of their illness was 83% (20 of 24 patients), compared to an incidence of 41% (7 of 17) in patients first examined greater than 1 week after onset of disease (P = 0.004). There was no difference in the uveitis, vs. the non uveitis groups with respect to age, sex, race or subsequent aneurysm formation as a complication of their Kawasaki syndrome. The mean erythrocyte sedimentation rate was not different in the two groups. Anterior uveitis is a common finding early in the course of Kawasaki syndrome. Slit lamp examination may be a helpful clinical tool in identifying patients with Kawasaki syndrome, and uveitis should be considered for inclusion in the Centers for Disease Control case definition of Kawasaki syndrome. PMID- 4039820 TI - Prevalence and significance of cryptosporidiosis in children. PMID- 4039821 TI - Diurnal, premating, and postmating testosterone levels in roosters genetically selected for mating frequency. AB - Circulating testosterone (T) levels were measured in roosters from lines genetically selected for high (HM) and low (LM) mating frequency and the randombred control (AC) base population. Lights were provided from 0600 through 2000 hr. A dirunal profile was determined by sampling at 0600, 1200, 1800, and 2400 hr. Plasma T levels prior to mating, immediately after mating, and 1 and 3 hr after mating were measured. By 1800 hr, AC males had higher T levels than both HM and LM males, which had levels that were similar to each other. Testosterone was at a minimum at 0600 hr and peaked at 2400 hr. Lines differed significantly both before and after mating with AC males highest, HM males intermediate, and LM males lowest. Control males had higher than baseline values prior to and after mating. Testosterone levels of AC males were correlated with their mating frequencies. PMID- 4039822 TI - Liver response to diet and estrogen in white Leghorn and Rhode Island Red chickens. AB - Experiments were conducted to compare the response of Rhode Island Reds (RIR) and White Leghorns (WL) to estradiol (E2) administration and diets of different composition. In growing chickens injected with E2 for 7 days, RIR accumulated significantly more hepatic lipid and had significantly less plasma lipid than WL. Both RIR and WL, injected for 4 days with E2, had lower hepatic lipids when fed a diet containing fish meal, alfalfa meal, and torula yeast (FAY) than when fed a corn-soybean meal diet (CS). Plasma glutamic oxaloacetic transaminase activity was significantly lower for RIR. Feeding a FAY diet to laying hens significantly reduced hepatic lipids in WL but not in RIR. Implantation of tubes containing E2 in RIR-laying hens resulted in a significant body weight loss and 25% mortality, while a similar treatment in WL-laying hens caused no body weight loss or mortality. Injecting both RIR and WL-laying hens with E2 caused a marked body weight loss and high mortality in both breeds although WL were less severely affected. The results show that breeds of chickens respond differently to both E2 administration and changes in diet composition. PMID- 4039823 TI - [Comparative thin layer chromatography studies of two psilocybes and a hallucinogenic inocybe]. PMID- 4039824 TI - Role of urine in coordinating reproduction in a desert rodent (Dipodomys merriami). AB - Detection of reproductive status from chemical signals in the urine of a desert rodent was examined. Intact and castrated male and estrous (induced) and nonestrous (ovariectomized) female Dipodomys merriami were tested for their preferences for various combinations of water and urine from intact males, estrous females, castrated males, and nonestrous females. Intact and castrated males were also tested for their responses to urine from females at different stages of the reproductive cycle: proestrus, estrus, and diestrus. Neither intact nor castrated males exhibited a preference for urine from females in any stage of the estrous cycle. Urine from intact males, however, was preferred by both intact males and estrous females. Urine from reproductively active males, rather than from estrous females, seems to contain information for coordinating reproduction in D. merriami. PMID- 4039825 TI - Habituation of the prolactin response in rats to psychological stress. AB - It is well known that stress is a stimulant for prolactin release. However, relatively few studies have investigated the role of psychological factors in prolactin secretion, and investigators have typically used one-time exposure and a single collection period in their studies. In our studies, attempts were made to carefully characterize the prolactin response to different psychological stressors by serially sampling blood from an indwelling cannula and to determine if repeated exposure to the stressor leads to habituation of the prolactin response. Exposure of the male rats to different novel situations such as being placed in a new cage, being placed on a platform in water, or being handled resulted in increased prolactin levels. As the rats habituated behaviorally to repeated exposure to similar situations, the prolactin response also attenuated. These findings show that psychological factors do play a role in influencing prolactin secretion and are consistent with the idea that as the psychological stress imposed by a stimulus becomes habituated, the prolactin response to that stimulus also becomes habituated. PMID- 4039826 TI - The herpes simplex viruses: the facts health professionals need to know. AB - Herpes labialis and herpes genitalis are described, including the symptoms, complications, treatment, and research of the disease. The article explains how transmission or contraction of the herpes virus occurs, particularly in the hospital setting, and how it can be avoided by the health professional. PMID- 4039827 TI - Accessory spleen compromising response to splenectomy for idiopathic thrombocytopenic purpura. AB - Accessory spleens were sought in 28 patients who had undergone splenectomy for chronic idiopathic thrombocytopenic purpura (ITP), using a variety of techniques. Abdominal scintigraphy with autologous erythrocytes labeled with Tc-99m and opsonized with anti-D IgG (radioimmune method) proved to be most useful, clearly demonstrating one or more accessory spleens in 12 cases (43%). Computed tomography (CT) was also helpful. Four out of five patients demonstrated an increased platelet count following surgery, the effectiveness of which was illustrated by the radioimmune scan. Patients who have had splenectomy for chronic ITP should be scanned using radioimmune techniques and CT to determine whether an accessory spleen is present. PMID- 4039828 TI - Morphine and clonidine oral self-administration: a study in morphine dependent or abstinent rats. AB - The ability of morphine and of clonidine to support self-administration has been evaluated in morphine dependent or abstinent rats, using an orally reinforced operant technique (F.R. 20). It was found that: Morphine drinking can function as a reinforcer of an operant response both in dependent and abstinent rats. The bitter taste of morphine becomes a secondary reinforcer for rats usually working for the alkaloid. Clonidine supports oral self-administration in morphine abstinent, but not in morphine dependent rats. The data are in line with clinical findings and give a further evidence that oral self administration in rats can be an useful model for the analysis of drug dependence. PMID- 4039829 TI - Radioimmunoassay for fibroblast growth factor (FGF): release by the bovine anterior pituitary in vitro. AB - A radioimmunoassay (RIA) was developed to measure fibroblast growth factor (FGF) using antiserum generated against a synthetic replicate of [Tyr10]FGF(1-10). The antisera, previously shown to be capable of inhibiting the biological action of FGF on bovine aortic arch endothelial cells in vitro, are highly specific for the amino-terminus of FGF. In the RIA, the antisera recognize the decapeptide antigen [Tyr10]FGF(1-10) and the intact mitogen on an equimolar basis and show less than 0.01% cross-reactivity with N-acetyl-[Tyr10]FGF(1-10). Bovine adenohypophysial cells maintained in primary monolayer culture release and ir-FGF which is indistinguishable from the intact mitogen in as much as it is retained on heparin Sepharose affinity columns and shows a dose-dependent and parallel displacement in RIA. The release of ir-FGF by the bovine adenohypophysis can be increased with forskolin (10(-5) M) or KCl (50 mM). Preincubation of pituitary cells with 17 beta-estradiol has no measurable effects on basal ir-FGF, but increases the release after KCl treatment 2-3-fold. These results show that ir-FGF can be released by the bovine adenohypophysis in vitro and lend credence to the hypothesis that FGF plays a physiological role in the homeostatic mechanisms regulating mesoderm-derived cell growth. PMID- 4039830 TI - [Intra-arterial administration of cytostatics with obstructed blood flow. Preliminary study in 7 patients with hypernephroma treated with cisplatin]. PMID- 4039831 TI - [Membranous subaortic stenosis associated with pulmonary infundibular stenosis (double outlet right ventricle). Presentation of a case and review of the literature]. PMID- 4039832 TI - [Effects of immobilization stress in utero on the course of pregnancy in the rat and on various parameters in the newborn animals]. AB - The effects of immobilization stress applied during pregnancy on the evolution of pregnant rats and on the fetus and newborn have been studied. Results show alterations in food intake during pregnancy as well as in the weight of some measured structures in 21 day old fetuses. There was similarly found a significant increase in the number of dead newborn. The effect of immobilization stress applied in utero upon the evolution of pregnancy, fetus and newborn, is discussed. PMID- 4039833 TI - [Effect of adrenaline and phenylephrine on milk extraction during the mechanical milking of cows]. AB - During mechanical milking in the morning between days 60 and 130 of lactation, 6 or 10 French Friesian Pie-Noire (FFPN) cows were given an intrajugular injection of 0.3 mg of adrenaline or 5 mg of phenylephrine (table 1). The treatments, each given 7 times to each cow, were alternated every other day with a control injection of 0.9% NaCl. The adrenaline caused: - a non-significant decrease in total milk yield (-4.9%: 11.57 l vs 12.17 l with NaCl) and in the volume of machine-stripped milk (0.360 l vs 0.430 l with NaCl); - an increase (+8.7%) in milk flow (1.165 l/min vs 1.072 l/min with NaCl; table 4). Phenylephrine caused a significant 10% reduction in total milk yield (13.35 l vs 14.84 l with NaCl) but had no effect on the volume of machine-stripped milk (0.235 l vs 0.295 l with NaCl) or on milk flow (0.961 l/min vs 0.962 l/min with NaCl; table 3). In agreement with our previous results (Bernabe and Peeters, 1980; Bernabe and Ricordel, 1985), beta-receptor (adrenaline) stimulation appeared to increase milk flow by relaxing the teat muscles. However, when contact was avoided between the teats and the milking machine, the stimulation of teat alpha-receptors (phenylephrine) did not inhibit milk flow. It is supposed that during milking the machine caused the teat tissue to contract enough to mask the effect of the alpha mimetic treatment on milk flow. PMID- 4039834 TI - Presynaptic stimulation of dopaminergic CNS structures in sheep as a mechanism of immobilising action of Immobyl (fentanyl + azaperone). AB - The immobilising action of Immobyl (fentanyl : azaperone, 5:1) in six sheep has been analysed on the basis of the changes in dopamine, noradrenalin, adrenalin, homovanillic acid and 5-hydroxytryptamine concentrations in the corpus striatum, frontal motor cortex, pons, cerebellum and lumbosacral spinal cord as compared to the control animals which were given saline. Forty minutes after intramuscular injection of an immobilising dose (0.19 mg [kg bodyweight]-1), Immobyl caused a significant decrease in dopamine, noradrenalin and 5-hydroxytryptamine concentrations and a similarly large decrease in homovanillic acid concentration (47 per cent) in the corpus striatum with a simultaneous but insignificant increase in the concentrations of these substances in the frontal motor cortex region. In Immobyl immobilisation, sheep showed a significant increase in dopamine concentration with an equally significant decrease in homovanillic acid concentrations in the lumbosacral part of the spinal cord. It is suggested that fentanyl stimulates the presynaptic dopamine receptors in the corpus striatum in sheep, significantly decreasing synthesis and release of dopamine and noradrenalin and intensifying an inhibitory effect of the corpus striatum on locomotor activity and thus causes the immobilisation of the animal. PMID- 4039835 TI - Respiratory functional changes on intratracheal challenge of sensitized rats. AB - Inbred PVG/c rats were sensitized to DNP19-ovalbumin by intraperitoneal injection. Sensitized rats when challenged with antigen developed characteristic brief interruptions of expiratory flow ('expiratory notching'). The functional residual capacity fell in rats challenged with antigen or saline but the fall was greater in those sensitized rats challenged with antigen. No greater alterations in respiratory rate, minute volume, airways resistance or dynamic compliance occurred on antigen as compared with saline challenge of sensitized rats, suggesting that the expression of immediate respiratory hypersensitivity in the rat is different from the asthmatic response in humans. The expiratory notching was reduced if an additional airways resistance was added in series to the tracheostomy tube. This may be explained as a result of reduction in the dynamic compression which normally produced the expiratory notching. PMID- 4039836 TI - [A case of tunnel subaortic stenosis associated with patent ductus arteriosus with severe pulmonary hypertension in a middle-aged woman]. PMID- 4039837 TI - Oxygen supply and limiting oxygen pressures in an insect larva. AB - Larvae of the moth, Carpocapsa saltitans, demonstrate a diurnal activity pattern of rhythmic twitching which, under conditions of controlled light and temperature, is characterized by a predictable frequency and regularity. The twitching activity is shown to be sensitive to the partial pressure of environmental oxygen, and it ceases altogether at a particular PO2 called 'critical'. Use is made of the 'critical' PO2 in normobaric and hypobaric conditions to deduce the roles of diffusion and convection in the larval oxygen transport mechanisms; and also as a value for the total decrement of PO2 from ambient air to mitochondria, in order to evaluate predicted values based on calculations of resistance to oxygen flow. For this latter study 'porosity' of the larva and the seed pod in which it is normally housed was inferred from measured rates of water vapor loss, and oxygen uptake rates of the larvae were measured by the manometric technique of Warburg. Applying these data to a model system the conclusion was reached that almost the total resistance to oxygen flow is at the spiracle. PMID- 4039838 TI - [Do androgens have a therapeutic role in hematology?]. PMID- 4039839 TI - Studies on the causation of adverse reactions in microfilaraemic host following diethylcarbamazine therapy (Dipetalonema viteae in Mastomys natalensis). AB - The mechanism of the adverse reaction in microfilaraemic subjects following diethylcarbamazine (DEC) therapy has remained an enigma. To study the mechanisms involved Mastomys natalensis infected with Dipetalonema viteae have been used. Animals showing up to 50 mf/5 cmm of blood did not show any perceptible reactions when treated with the minimum effective dose of 350 mg/kg of DEC citrate, while those having more than 80 mf/5 cmm died, suggesting an intensity dependent severity of reactions. Infective larvae contained maximum amounts of biogenic amines followed by mf and adults in that order. 16 mg of histamine or 24 mg of 5 hydroxytryptamine caused death when injected into healthy animals, whereas sonicated mf (5 million) and adult somatic products (4 mg protein) did not, signifying that the biogenic amine contents of the parasites were less than the critical level to cause death. Adult somatic products did not produce any visible reactions when injected into animals with microfilariaemia, but sonicated mf (5 million) caused death. It is concluded that the adverse reactions seen after DEC treatment are due to the release of biogenic amines in an anaphylactic type of reaction subsequent to massive release of parasite antigen in a sensitised host, which is directly proportional to the intensity of microfilaraemia and that the adverse reactions are not due to liberation of endogenous biogenic amines from dead mf. PMID- 4039840 TI - [Extent of endemic yaws in Upper Volta in 1981]. AB - This yaws investigation has been realized in the South West of Upper-Volta, in 1981, in areas around Gaoua, Niangoloko, N'Dorola; this investigation concerns 15 villages, chosen at random, and a sample of 1540 persons older than 4 years. The clinical prevalence (infectious cases) is 0.6%; the higher prevalence is observed around Gaoua (1.5%). Infectious contagious lesions are found especially in the 5 14 years old group. This investigation shows a low prevalence (under 5%) of active yaws. The serological prevalence (Kline-test) is 5.8% and we observe also around Gaoua the highest prevalence (8%). Periodical screening surveys of the population, during years 1952-1957, had shown a low prevalence of yaws, with a medium prevalence of yaws around Gaoua. Yaws treatment campaigns had been realized from 1957 to 1960 in South-West of Upper-Volta with very good results (prevalence: 0.06% - 1960). Now, in 1981, we note a resurgence of endemic foci, especially around Gaoua, from where the infection is spreading again, this, threatening the gains made by previous mass treatment campaigns. Taking in account the present result, it is necessary to treat contagious cases and contact sick persons (selective mass treatment or S.M.T., recommended in areas of low prevalence, by the WHO scientific group on treponemal infections). PMID- 4039841 TI - Isoprenoid biosynthesis in filariae. PMID- 4039842 TI - Energy generation in filariae--a target for chemotherapy. PMID- 4039844 TI - [Primary obstructive and hypertrophic myocardiopathies]. PMID- 4039843 TI - The significance of morphological studies on macrofilariae from onchocerciasis patients for the evaluation of control measures. PMID- 4039845 TI - [Spinal hyperostosis and disorders of retinol metabolism]. AB - Vitamin A or its acid derivatives can be responsible for bony lesions similar to those in ankylosing hyperostosis in animals and in man. We performed a controlled, prospective study on vitamin A metabolism in 23 patients with ankylosing hyperostosis and in 17 normal controls. Beta-carotene serum levels were determined by spectrophotometry, and retinol serum levels by inverse phase high performance liquid chromatography, and retinol binding protein (RBP) by radial immunodiffusion. After eliminating the causes which disturb vitamin A metabolism or RBP, we found a significant increase in retinol (p less than 0.02), in the molar relationship, retinol/RBP (p less than 0.05), without zinc deficiency. The association of diabetes with ankylosing hyperostosis normalizes in a statistically significant manner serum retinol levels (p less than 0.05), but apparently does not modify the increased molar relationship, retinol/RBP. These findings suggest a toxic effect of retinol due to the increased amount of free retinol or by nonspecific transport by proteins other than RBP. PMID- 4039846 TI - Splenic pulp, plasma cells and foamy histiocytes in immune thrombocytopenia: combined morphometric immunohistochemical and ultrastructural studies. AB - Spleens from 16 splenectomized patients with immune thrombocytopenia (ITP) were compared with 10 controls (accidental and incidental splenectomy, staging laparotomy). Fresh unfixed material was secured for smears and cryostat sections, and splenic tissue was fixed by perfusion for histomorphometric, immunohistochemical and ultrastructural examination. The volumes of white pulp, including germinal centres, red pulp, and trabeculae and vessels were estimated. The ratio plasma cells containing various Ig-classes/total nucleated cells and the ratio immature/mature plasma cells were determined and the occurrence and character of foamy cells examined. There were slightly increased absolute volumes of white pulp, red pulp and trabeculae + major vessels in ITP, but the differences were not statistically significant. There was a statistically significant raised number of IgG-, IgA- and IgM-containing plasma cells in the germinal centres in ITP. More IgG-containing cells seemed to be immature than in controls, but the difference was not statistically significant. Light microscopy showed foamy histiocytes in 7 of 16 cases, but electron microscopy showed them in all cases of ITP. Foamy histiocytes reacted with antithrombocyte serum. PMID- 4039847 TI - [Acute interstitial nephritis and uveitis: a recently recognized syndrome]. AB - The case is described of a 14-year-old boy who presented with a 6-week history of fatigue, severe weight loss (15 kg) and glycosuria. On admission he was in non oliguric renal failure (serum creatinine 1360 mumol/l) with moderate proteinuria (1.3 g per 24 h), glycosuria (9.5 g per 24 h) and generalized aminoaciduria. Renal biopsy showed acute interstitial nephritis (AIN) with severe mononuclear cell infiltration. No etiology was found. The patient required hemodialysis (5 times) and responded dramatically to therapy with prednisone (initially 75 mg per day), which was discontinued after 2 months. He presented again 11 weeks after admission with iridocyclitis of the right eye, and 2 months later with the same condition in the left eye. Response to local application of steroids was slow. The association of AIN with uveitis has so far been reported in 12 other pediatric patients aged 10 to 16 years, and in one adult patient; 64% were female. Uveitis often recurred, in contrast to nephritis. The etiology of the syndrome is unknown, a transient defect in cell-mediated immunity being postulated. PMID- 4039848 TI - Why do inbred mice evolve so quickly? PMID- 4039849 TI - Thrombotic thrombocytopenic purpura in pregnancy: response to plasma manipulations. AB - We present three cases of thrombotic thrombocytopenic purpura (TTP) and one case of the hemolytic-uremic syndrome (HUS) occurring during pregnancy. All patients and their offspring survived, and none of the infants had TTP or HUS. Plasma manipulations (exchange and infusions) were the effective therapeutic measures in all patients. The most significant complication of therapy was posttransfusion hepatitis, which occurred in three patients, and from which recovery was complete. PMID- 4039850 TI - [Phospholipids and platelet procoagulant activity in myeloproliferative syndromes]. PMID- 4039851 TI - [Importance of genetic factors and allergy in the occurrence of chronic bronchitis (a study of twins)]. AB - The authors evaluate the qualitative and quantitative parameters characterizing hereditary predisposition to chronic bronchitis, both non-obstructive and obstructive patterns. The relationship was studied between allergoses and individual types of chronic bronchitis to establish the primary effect of allergy on the formation of chronic obstructive bronchitis as compared with chronic non obstructive bronchitis, which was found to have a lower coefficient of heredity. Based on the difference in the proband concordance in mono- and dizygotic twins in respect of allergy the role of hereditary predisposition to the disease was revealed. The effects of some acute infectious respiratory diseases on the development and course of chronic bronchitis were studied. PMID- 4039852 TI - Modulation of tissue fibrinolysis from hypoxia and hyperoxia. AB - The effects from alterations in inspired oxygen tension on the fibrinolytic activity in vessel walls was studied in rats. Tissue plasminogen activator activity was measured semiquantitatively with the histochemical technique. During severe hypoxic conditions (FIO2 = 0.05) the fibrinolytic activity in the aorta was significantly reduced as compared to control animals. At 24 hours with slightly higher oxygen tension (FIO2 = 0.08) the activity was increased. When breathing pure oxygen (FIO2 = 1.0) the fibrinolytic activity was increased in the aorta after 8 hours. Following chronic hypoxia for 6 weeks (FIO2 = 0.1) the activity in the caval vein was increased. Changes in inspired oxygen tension thus affected the endothelial cells and changed their expression of plasminogen activator activity. PMID- 4039853 TI - Ultrastructure of cyclic changes in the murine uterus, cervix, and vagina. AB - The regional and cyclic changes in the murine genital epithelium were studied by transmission and scanning electron microscopy to provide a morphological standard to serve as a basis for investigation of host-parasite relationships in genital infections. Thus, we examined not only mucosal epithelial cell changes, but also surface mucus, normal flora and inflammatory cells. Ultrastructurally, at proestrus/estrus, we found uterine and most cervical epithelial cells covered with microvilli overlaid with mucus-like secretions and evidence of internal secretory activity. There was little normal flora anywhere in the tract. At early metestrus, we found squamous cervicovaginal epithelial cells with low discontinuous microrugae, extensive normal flora and many neutrophils beginning to migrate through the epithelium. The flora and neutrophils could explain the relative lack of susceptibility to infection at that time. At diestrus the appearance of a newly regenerated epithelium and lack of normal flora suggested that initiation of infection could occur at this stage; however, the presence of large numbers of neutrophils ready to phagocytize invading bacteria indicated a deterrent to infection. This study of cyclic changes in flora, mucus, neutrophils and epithelial cells provided ultrastructural evidence to support an earlier hypothesis that the greatest susceptibility to gonococcal infection in mice occurred at proestrus/estrus. PMID- 4039854 TI - Coronary arterial lesions in piglets from sows fed moderate excesses of vitamin D. AB - Ultrastructural studies were conducted on the coronary arteries of 6 week-old piglets from sows which received diets containing either 25 micrograms or 3.7 micrograms of vitamin D3 per pound of basal ration. The subendothelial space which was rich in mucopolysaccharide and newly formed tiny elastic fibers, contained numerous macrophages, some of which possessed lipid droplets. Degenerated smooth muscle cells with pyknotic nuclei or vesiculated organelles, and mitotic smooth muscle cells were occasionally seen in the coronary artery. Piglets from sows which were fed high doses of vitamin D had more degenerated smooth muscle cells without stainable lipid and lipid containing cells in their coronary arteries than piglets from sows which were fed low doses of vitamin D. These results suggested that an excess dietary intake of vitamin D by pregnant animals may have potential angiotoxic effects on the coronary arteries of their offsprings. PMID- 4039855 TI - Distribution and binding of [14C]acrylamide to macromolecules in SENCAR and BALB/c mice following oral and topical administration. AB - To determine if differences in acrylamide distribution or its binding to DNA could be responsible for the reported higher incidence of skin papillomas observed after oral administration compared to topical application, [14C]acrylamide was administered by topical application and oral intubation to male SENCAR and BALB/mice. Portions of lung, liver, stomach, testes, and skin were removed, and 14C was measured at 15 min, 30 min, 1, 6, 12, 24, and 48 hr. Binding to DNA, RNA, and protein was measured at 6 and 48 hr. Following oral administration, few strain differences in distribution or binding were noted. After topical application, SENCAR mice generally showed higher tissue concentrations than did the BALB/c mice at the early time periods but not at the later ones. Comparing the two routes, comparable concentrations were observed in all tissues except the skin where the amount of [14C]acrylamide after topical application was approximately 100 times that observed after oral administration. At 48 hr, binding to DNA was sevenfold higher after topical than after oral administration. The effect of route on papilloma formation cannot be explained, therefore, on the basis of either a difference in distribution or binding to DNA in the target organ. The binding of acrylamide to DNA in skin was similar in both SENCAR and BALB/c mice indicating that the much greater susceptibility of the SENCAR mice to tumorigenesis cannot be explained simply on the basis of distribution or macromolecular binding. PMID- 4039856 TI - The acute toxicity and teratogenicity of nickel in pregnant rats. AB - The increase susceptibility of the pregnant rat to intraperitoneally administered nickel (Ni) is apparent at 12 and 19 days of pregnancy and cannot be due, therefore, to the increase in total body weight. Teratogenic malformations occur when Ni is administered during organogenesis and are maximal at dose levels that are toxic for the dam. The yolk sac and chorioallantoic placentas accumulate Ni, but this does not prevent the transport of the metal to the embryo or foetus. The Ni concentrations in the conceptuses decrease more slowly with time than those in the maternal organs. In the foetuses, the decrease in concentration is due to the increase in weight, since the content of Ni increases between 4 h and 24 h. Foetal uptake of [14C]thymidine, [3H]leucine and 65Zn is unaffected at 3 h after the injection of the dam with 4 mg Ni/kg body wt. Incorporation of [3H]leucine into foetal protein, but not the incorporation of [14C]-thymidine into DNA, is decreased at this time. A major effect of treatment with this teratogenic dose is an increase in the maternal plasma glucose concentration which, in turn, alters the supply of the sugar to the foetus. The possible relevance of temporary foetal hyperglycaemia to teratogenesis is discussed. PMID- 4039857 TI - [Effect of combined treatment with cisplatin and radiation on the survival of Chinese hamster cells]. AB - During combined treatment of Chinese hamster cells with cisplatinum and irradiation under aerobic conditions, there appear interactions between the two treatment modalities depending on the treatment sequence and the time interval. Treatment with cisplatinum followed by irradiation leads to a reduction of the shoulder of the survival curve with increasing time interval. Simultaneous treatment with cisplatinum and irradiation under aerobic or hypoxic conditions does not change the survival curve. Treatment with cisplatinum under aerobic conditions followed by irradiation in hypoxia does not lead to any interaction of both modalities independent of the time interval in contrast to subsequent irradiation under aerobic conditions. The specific sensitization of hypoxic cells by cisplatinum towards irradiation described in the literature could not be demonstrated with our cell line. PMID- 4039858 TI - Idiopathic hypertrophic subaortic stenosis and cerebral ischemia. PMID- 4039860 TI - Isolation of the agent causing cutaneous leishmaniasis in Italy and its visceralization in inbred hamsters. PMID- 4039859 TI - The radioallergosorbent test (RAST) for the serological diagnosis of human anisakiasis. AB - The serum of patients with parasitologically confirmed and one patient with a clinically presumptive case of anisakiasis were tested by the radioallergosorbent test (RAST) and counter-electrophoresis (CEP) for IgE and IgG antibodies, respectively, using antigens prepared from larval (L3) stage Anisakis simplex and larval (L2) stage Toxocara canis. All sera were RAST-positive to the A. simplex antigen and RAST-negative to the T. canis antigen. All sera were CEP-negative to both antigens. The presence of a specific IgE antibody suggests that the RAST could serve as a useful technique for the serodiagnosis of anisakiasis in man. PMID- 4039861 TI - [Protein metabolism in the cerebral hemispheres during the emotional-algesic stress]. AB - Emotional-algesic stress causes essential changes in the protein metabolism of cerebral hemispheres. These changes may be of great importance for the functioning of the brain and cause the disturbances of the higher nervous activity when the organism is influenced by the emotional stress factors. PMID- 4039862 TI - [Oxidative phosphorylation in the rat liver mitochondria under activation of lipid peroxidation]. AB - The immobilization stress and oxygen effect under pressure of 0.8 atm (hyperbaric oxygenation) considerably activate lipid peroxidation both in the blood serum and rat liver mitochondria. Inhibition and partial separation of oxidative phosphorylation being more pronounced with intensification of lipid peroxidation are simultaneously observed. PMID- 4039863 TI - [The immune system and primary open-angle glaucoma]. PMID- 4039864 TI - [Retinal macroaneurysms]. PMID- 4039865 TI - [Prevention of post-traumatic immunosuppression with dimexide]. AB - Experimental studies in mice have shown that Dimexid injected after trauma can protect the immune system from inhibiting effects of trauma factors. Dimexid when used in the complex treatment of a severe mechanical trauma can reduce the risk of posttraumatic infectious complications. PMID- 4039866 TI - Effects of vasopressor drugs on number of Trypanosoma congolense in ruminant blood. AB - The effects of intravenous administration of vasopressor drugs on parasite concentration was studied in cows and sheep infected with Trypanosoma congolense. Ephedrine (USP), adrenaline (BP) and insulin increased jugular concentration of the parasite. Maximum effects were reached between 1 1/2 and 2 h with ephedrine and at 2 1/2-3 h with adrenaline. Increases in parasitaemia resulting from epinephrine were sustained only in sheep and adrenaline gave similar effects in both ruminants. Only epinephrine significantly increased parasitaemia within 45 min of administration. Ephedrine, hydralazine and guanethidine had no significant effects on parasitaemia. It is suggested that one of the mechanisms by which trypanocides increase jugular concentration of T. congolense may be by vasoconstriction of the capillary endothelium. PMID- 4039867 TI - Comparative susceptibility of embryonated hen eggs and pig lung alveolar macrophages to chlamydial infection. AB - Pig lung alveolar macrophages provided a suitable cell culture system for primary isolation of ovine chlamydia and sustained their growth through several passages. In centrifuged preparations, titres of established strains compared favourably with those obtained in fertile eggs, and in parallel titrations on primary isolation, evidence of chlamydial infection was detectable in macrophages several days earlier than in eggs. PMID- 4039868 TI - [Biological value of various types of dietary soy bean proteins]. AB - Chemistry and experiments on animals (male Wistar rats) were made to determine the biological value of 4 samples of soybean proteins: 2 protein isolates (Ardex SP-6 and Ardex-M, ADM USA); soybean protein concentrate (UNICO, UNIMILS, Holland), and textured soybean concentrate (manufactured by the All-Union Research Institute of Fat). The content of essential amino acids and amino acid score of the protein samples were measured relative to three standard aminograms. The "growing" (the protein efficacy ratio and net protein ratio) and balance (net protein utilization) characteristics of the biological value were determined in experiments on rats fed diets containing soybean proteins as the only source of proteins (10% of caloric value). The Dtr of the proteins under study was defined. All the evaluable proteins were found to be almost similar as regards the biological value. The Dtr of protein isolates was discovered to be higher as compared to that of soybean protein concentrates. PMID- 4039869 TI - [Herpes simplex virus infections]. AB - There are two serological types of herpes simplex virus, HSV-1 and HSV-2. The types can be differentiated by different methods. After a primary infection HSV reaches the sensory ganglions by the way of peripheral nervous tracts. The virus remains for life in the ganglion as virus genome. After activation and return movement a new infection can appear. A lot of various diseases are caused by primary infection, reactivation or reinfection. The diagnosis in herpes virus diseases includes the detection of virus or viral antigens and the demonstration of specific antibodies against HSV. Effective antiviral drugs are available for chemotherapy of HSV-infection. Acyclovir is a beneficial drug without toxic secondary effects. The prevalence of HSV-antibodies in the population is very high. PMID- 4039870 TI - Comparative biological activities of whole cell pertussis vaccine and a new acellular preparation. AB - The biological activities of whole-cell pertussis vaccine and a new acellular preparation were compared. It was observed that both preparations were similarly effective in inducing protection in mice against intracerebral challenge with B. pertussis, however, the acellular preparation was approximately 200-fold more potent. A close relationship between the degree of pertussis toxin purification and the increase in potency was observed. Neither preparation affected the weight gain of the animals within the doses employed. As expected, both preparations had histamine-sensitizing activity and leukocyte-promoting activity. It is suggested that this preparation, obtained using very simple methodology, can be considered as a potentially useful acellular pertussis vaccine. PMID- 4039871 TI - [Usefulness of urethrocytologic studies in urinary incontinence]. AB - Comparative cytological studies were conducted in urethra and vagina of 40 women with stress incontinence, another 40 with urge incontinence and 53 clinically intact women for morphological assessment of urinary incontinence. Evaluation was based on maturation index, maturation value, and dynamic estrogenicity index. During sexual maturity no significant difference regarding proliferability of urethral and vaginal epithelium was found existing between clinically intact women and patients with stress or urge incontinence. Differences of maturation values above 30 between urethral and vaginal cells were recordable only from post menopause patients with urge incontinence, providing for certain possible conclusions as to the form of urinary incontinence. However, in post-menopause patients, oral and vaginal estriol therapy was followed by significant rise in intermedial and superficial cells in both organs. Improvement of stress and urge incontinence was recordable subjectively also from estriol therapy during sexual maturity, independent from urethral or vaginal cell patterns. Hence, urethral cytology is only conditionally suitable for differential diagnosis and optimization of therapy of urinary incontinence. Primarily it is suitable to coping for disturbances of micturition with an uncharacteristic urinary urge symptomatology or chronic urethritis. PMID- 4039872 TI - Cryptosporidium causing severe enteritis in a Belgian immunocompetent patient. PMID- 4039873 TI - Food consumption and mouse-killing in Sprague-Dawley rats. AB - The effects of daily 10-min mouse exposure tests on food consumption were studied in killer and non-killer Sprague-Dawley rats. The results showed both mouse killers and non-killers significantly to decrease their food consumption when tested daily for mouse-killing. The effect was more pronounced in mouse-killers than in non-killers and the day-to-day individual fluctuation of food consumption was greater in mouse-killers during the mouse confrontation period. PMID- 4039874 TI - Interaction of chemical and psychogenic stress: biochemical response to repeated "conditioned fear" and chronic carbon disulphide poisoning. PMID- 4039875 TI - Cow's milk, soya milk and goat's milk in a mother's diet causing eczema and diarrhoea in her breast fed infant. AB - An exclusively breast fed infant developed eczema and severe gastrointestinal symptoms when his mother took cow's milk or goat's milk, and eczema alone when she took soya milk. The cow's milk- and soya milk-induced symptoms were reproduced by double blind challenge. PMID- 4039876 TI - Serum melatonin in relation to clinical variables in patients with major depressive disorder and a hypothesis of a low melatonin syndrome. AB - Maximum nocturnal serum melatonin level (MTmax) in relation to some clinical variables was studied in 32 patients with a major depressive episode and in 33 healthy subjects with reference to the outcome of the dexamethasone suppression test (DST). Significant regressions were found between MTmax levels and clinical rating scores in CPRS, interpreted as retardation symptoms. Four healthy subjects with disposition for dysthymic reactions had subnormal MTmax levels, which differed from MTmax levels in subjects without such disposition. Patients but not the healthy subjects, who reported parental loss before 17 years of age, had subnormal MTmax levels and differed from patients with no reported parental loss. Patients with no reported suicidal behaviour in clinical history had significantly lower MTmax levels than patients with reported suicide attempts. No relations were found between low MTmax levels and diagnoses, duration of illness, reported inheritance for depressive illness or sleep disturbances. A hypothetical low melatonin syndrome in depression is proposed: low nocturnal melatonin, abnormal dexamethasone suppression test, disturbed 24-h rhythm of cortisol, less pronounced daily and annual cyclic variation in depressive symptomatology. PMID- 4039877 TI - Relationship of dysphoric premenstrual changes to depressive disorders. AB - An association between premenstrual dysphoric changes and depressive disorders is demonstrated in 170 women. Each woman underwent an evaluation for current and life-time diagnosis using the Research Diagnostic Criteria (RDC). Premenstrual dysphoric changes were evaluated with the Premenstrual Assessment Form (PAF). Criteria for PAF Full Depressive Syndrome were met by 57% of women with a life time diagnosis of Major Depressive Disorder. Only 14% of the Never Mentally Ill women met these PAF criteria. Eighty-four percent of those who had PAF Full Depressive Syndrome also had RDC Major Depressive Disorder while only 9% were Never Mentally Ill. PMID- 4039879 TI - The dynamics of rapid left ventricular filling in man. PMID- 4039878 TI - Posterior fossa haemangioblastomas: angiography versus computed tomography. AB - A series of 57 patients harbouring a total of 63 haemangioblastomas of the posterior fossa is reviewed. Some clinical data are pointed out and the findings of vertebral angiography and computed tomography scanning performed in 61 and 38 lesions, respectively, are examined. The results obtained in the last 38 cases, undergoing both examinations, are compared, and some notes on differential diagnosis with other expansive lesions of the posterior fossa are given. PMID- 4039880 TI - Apexcardiogram in the assessment of left ventricular function. PMID- 4039881 TI - Expression of isoforms from cloned skeletal and cardiac actin genes. PMID- 4039882 TI - Effect of propranolol on left ventricular relaxation in hypertrophic cardiomyopathy: an echographic study. AB - Many authors have shown that hypertrophic cardiomyopathy (HCM) is often associated with diastolic abnormalities. The purpose of this study was to determine the effect of propranolol on left ventricular isovolumic relaxation time (IVRT) measured by echocardiography in 20 patients with hypertrophic cardiomyopathy under basal conditions and under increasing doses of propranolol (160 mg, 320 mg, and 480 mg per day) and in two control groups, 10 patients with aortic stenosis, and 10 normal subjects. IVRT was less than 50 msec in all normal subjects, while it was always above this limit in aortic stenosis (77 msec +/- 8, p less than 0.001), and in hypertrophic cardiomyopathy (94 msec +/- 19, p less than 0.001), with also a significant difference between these two last groups (p less than 0.01). Under increasing doses of propranolol, relaxation time often shortens gradually until 50 msec or less. These results show an improvement in left ventricular relaxation dependent on the propranolol dosage and often a normalization at high dosages. PMID- 4039884 TI - Herpetic vulvovaginitis and child abuse. PMID- 4039883 TI - Thallium perfusion and cardiac enzyme abnormalities in patients with familial hypertrophic cardiomyopathy. AB - Twelve patients of five families with familial hypertrophic cardiomyopathy were examined. Within each family, the older patients showed dilation or diminished contraction of the left ventricle by echocardiography or angiocardiography more frequently than did younger patients. LDH1 fraction (lactic dehydrogenase isoenzyme) and MB-CPK (creatinine phosphokinase isoenzyme) were increased in 7 of 10 patients. Thallium-201 myocardial scintigraphy showed perfusion defect or hypoperfusion in 9 of 10 patient. Eleven cases demonstrated remarkable hypertrophy at the macroscopic level. Marked fibrosis was observed in all 5 of the 11 patients whose histologic findings were obtained. In two necropsy cases, disarray was found throughout the right and left ventricles and the pattern of fibrosis was massive. These findings were different from those of ordinary hypertrophic cardiomyopathy. It is possible that each patient with familial hypertrophic cardiomyopathy may develop more prominent thallium and enzyme abnormalities as he becomes older, regardless of whether he develops a dilated cardiomyopathy picture. PMID- 4039885 TI - The problem of genital herpes in prepubertal children. PMID- 4039886 TI - Perinatal risks of neurodevelopmental handicaps. PMID- 4039887 TI - Chronic granulomatous disease and Torulopsis infections. PMID- 4039888 TI - Interactions between opposite-sex dizygotic fetuses and the assumptions of Weinberg difference method epidemiology. AB - The Weinberg difference method in twin epidemiology may be subject to a major error related to a fundamental assumption that seems not to have been previously questioned. Results presented here indicate that the mortality of like-sex dizygotics (DZs) resembles that of monozygotics (MZs) much more than that of unlike-sex DZs, who are not representative of any other group. Unlike-sex twins enjoy a relative protection from fetal and neonatal mortality and probably from at least one effect of the transient perinatal hypoxia common for second twins. Unlike-sex twins develop, and maintain into adulthood, an intermediate gender phenotype with respect to integration of craniofacial growth. PMID- 4039889 TI - Stability of intravenous admixtures of aztreonam and ampicillin. AB - The stability of aztreonam and ampicillin in intravenous admixtures containing both drugs was studied. Each of the following drugs and combinations of drugs was added to both 5% dextrose injection and 0.9% sodium chloride injection: aztreonam 10 and 20 mg/mL, ampicillin sodium 5 and 20 mg/mL, aztreonam 20 mg/mL and ampicillin sodium 20 mg/mL, aztreonam 20 mg/mL and ampicillin sodium 5 mg/mL, aztreonam 10 mg/mL and ampicillin sodium 20 mg/mL, and aztreonam 10 mg/mL and ampicillin sodium 5 mg/mL. One of each of these admixtures was stored at 25 degrees C for 48 hours and 4 degrees C for seven days. At various storage times the admixtures were inspected for visual changes and 2-mL samples were examined microscopically for crystalline and particulate matter, tested for pH, and assayed by high-performance liquid chromatography. No visual changes were observed. In the two-drug solutions, pH was influenced by concentrations of the two drugs and stability of the drugs was influenced by the solution pH. The pH of single-drug aztreonam admixtures did not change during storage, but the pH of single-drug and two-drug admixtures containing ampicillin decreased. In single drug admixtures, aztreonam loss under both storage conditions was less than 10% but ampicillin loss was more than 10% in 0.9% sodium chloride injection and more than 50% in 5% dextrose injection. The stability of ampicillin was increased in the presence of aztreonam, and the stability of aztreonam was decreased in the presence of ampicillin.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4039890 TI - X-linked syndrome of branchial arch and other defects. AB - We report on two brothers and their maternal first cousin who have branchial arch defects and other anomalies. Similar physical findings in all three include microcephaly, downslanting palpebral fissures, highly arched palate, apparently lowset, protruding ears, bilateral hearing loss, slightly webbed neck, and mild short stature. In addition, two boys had cryptorchidism, and one had subvalvar pulmonic stenosis and body asymmetry. We suggest that these cousins have an X linked syndrome of which branchial arch defects are a component. Other pleiotropic manifestations of the mutant gene include microcephaly and cryptorchidism; body asymmetry and relatively short stature may be components as well. PMID- 4039891 TI - X-linked midline defects. AB - Opitz and Gilbert [Am J Med Genet 12:443-455, 1982] have postulated that the midline may be a kind of developmental field. Although developmental field defects (primary malformations) usually occur sporadically, in some instances they can be caused by a single gene mutation. We report on a family in which the occurrence of midline defects was consistent with X-linked inheritance. Anomalies present in the family include hydrocephalus, anencephaly, cleft lip, congenital heart defect, renal agenesis, and hypospadias. PMID- 4039892 TI - Unsuccessful treatment of fetal immunologic thrombocytopenia with dexamethasone. AB - Corticosteroid therapy near term for mothers with immunologic thrombocytopenia has recently been suggested as a clinically useful method to prevent neonatal thrombocytopenia. The unreliability of this approach is illustrated by the case of an infant with a low platelet count delivered after the maternal administration of dexamethasone. PMID- 4039893 TI - Hormone levels and premenstrual syndrome. PMID- 4039894 TI - Monozygotic twins concordant for bilateral Duane's retraction syndrome. AB - Duane's retraction syndrome applies to a wide spectrum of motility disturbances associated with retraction of the globe and narrowing of the palpebral fissure. Although many different anatomic and physiologic disturbances of the oculomotor system are implicated, the underlying cause remains obscure. Twin studies are often useful in determining the contribution of genetics or heredity to disease, but the occurrence of Duane's retraction syndrome in twins is rare. One of a pair of monozygotic twins concordant for bilateral Duane's retraction syndrome developed a 12-diopter esotropia in primary gaze but the other has not. Neither child has a head tilt and both can fix and follow with either eye. PMID- 4039895 TI - Surgical sequelae of abnormal eustachian tube function. AB - Mechanical, neural, and immunologic factors controlling eustachian tube function are discussed in detail. Relationships of normal tubal function to the development of otitis media with effusion and its pathologic sequelae are reviewed. PMID- 4039896 TI - Audiologic features of the X-linked progressive mixed deafness syndrome with perilymphatic gusher during stapes gusher. AB - Stapes gusher sometimes occurs at the moment the vestibule is opened. A flood of perilymph can be expected as a complication of stapes surgery in all males affected with the X-linked progressive mixed deafness syndrome. Audiologic features, such as a mixed hearing loss and elicitability of stapedial reflexes, are reported for eight affected males in a large Dutch family. PMID- 4039897 TI - Reversal of MAOI-induced anorgasmia with cyproheptadine. PMID- 4039898 TI - Probability-reward preferences of rhesus monkeys. AB - The relative preferences of rhesus monkeys for reward probability versus amount were investigated with procedures which contrasted general experience with specific instructions, and evaluated the relationship between probability-amount combinations and preference strength. Four stimulus objects, each signifying a different combination of reward frequency and amount (100% with one unit; 50% with two units; 33% with three units; or 25% with four units), were presented in pairs, one pair per daily session, with trial schedules providing the same amount of reward within each set of 12 trials. In Phase A, 4 monkeys (Group 1) were tested on the six choice-pairs with no preliminary training. In Phase B, Group 1 was joined by an additional 4 monkeys (Group 2), and each of the tasks was preceded by a demonstration of the relevant stimuli, one at a time, together with their associated probabilities and amounts. Group 1 animals developed preferences during Phase A for the more frequently rewarded objects, which persisted into Phase B, whereas Group 2 animals showed no preferences. This result indicates that preliminary instructions concerning the reward combinations associated with stimulus objects can prevent the development of a preference for greater probability over greater amount of reward, but cannot extinguish it once it has been formed or reestablished within the context of a particular task. PMID- 4039899 TI - Development of infective stage Leishmania promastigotes within phlebotomine sand flies. AB - Midgut promastigotes were obtained from Phlebotomus papatasi and Lutzomyia longipalpis on days 3-7 after infection with cloned isolates of Leishmania major and Leishmania mexicana amazonensis, respectively, and examined as to their ability to initiate cutaneous infections in BALB/c mice. Sequential development of midgut promastigotes from a noninfective to an infective stage was confirmed for both the New World and Old World species. The generation of infective promastigotes from rapidly dividing avirulent populations occurred as early as day 3 and was well under way by day 4 after infective feed. Optimally infective promastigotes were recovered from midguts shortly after bloodmeal passage, coinciding with the time at which another bloodmeal is sought by the fly. PMID- 4039900 TI - [Experimental study of the ototoxicity of cisplatinum]. PMID- 4039901 TI - [Clinical study of the ototoxicity of cisplatin]. PMID- 4039902 TI - [Chromosome abnormalities in male infertility]. AB - On the basis of systematic cytogenetic studies carried out with men undergoing examination for infertility in the couple, it is now estimated that the incidence of chromosome anomalies is about 5 per cent. This rate is much higher than that observed in the general population (0.7 per cent). Anomalies in the sex chromosomes are the most frequently observed since they represent approximately 4 per cent of the cases, and the analysis of the various types of mutation shows a distinct predominance of the 47 chromosome composition, XXY, which is related to Klinefelter's syndrome. Autosome anomalies are also observed, notably Robertsonian and reciprocal translocations. They are more rare (about 1% of the cases), but the fact that they are linked with disturbances of spermatogenesis is an important element in understanding the control-mechanisms of this process. The occurrence in both man and animals of a non-random relationship between the forms of translocation and the X and Y chromosomes found in the seminal vesicle during the pachytene stage, suggests that this contact interferes with the normal process in which the X chromosome is inactivated. This interference could account for the observed deficits in spermatogenesis. The hypothesis is reinforced by the fact that female carriers of the same autosome translocations, whose two X chromosomes are normally active during the whole miotic prophase, have no fertility problems. PMID- 4039903 TI - Screening for endometrial carcinoma by endouterine aspiration cytology with analysis of tumor markers in the aspirates. Development and application of a new screening technique. AB - A new endometrial aspiration technique for office screening of endometrial carcinoma without an anesthesia was studied. In patients without apparent signs of cervical canal stenosis, all of whom were 50 years of age or older, the aspiration attempt was successful in 96%. The aspirates were used for cytologic study and tumor marker assays. The results indicate that screening for endometrial carcinoma should be based on the determination of biochemical tumor markers in the uterine fluid. Lactate dehydrogenase (LD) is recommended as a primary marker, determined as total LD and as LD isoenzyme activity. Endometrial cytology is recommended as a supplementary screening technique in selected cases. PMID- 4039904 TI - Cisplatin and plasma iron levels. PMID- 4039905 TI - Thrombolytic treatment with recombinant tissue-type plasminogen activator in a patient with massive pulmonary embolism. PMID- 4039906 TI - [Hyperthyroidism caused by metastatic choriocarcinoma. A new male case]. AB - The authors report a case of hyperthyroidism induced by a metastatic choriocarcinoma (retroperitoneal, lungs, vertebral and epidural localisations) in a 49 year old man. Tachycardia and possibly weight loss were the only clinical signs of thyrotoxicosis. Chemotherapy led to a remission of hyperthyroidism and tumoral syndrome for 4 months. Neoplasia relapsed and circulating levels of thyroid hormones were increased during the final stages. This is the fifth male reported case of choriocarcinoma associated with hyperthyroidism. Many previous studies suggest that hyperthyroidism is induced by HCG thyroid stimulating activity. PMID- 4039907 TI - [Presentation and trial of a new medium-duration transtympanic ventilator]. AB - A new transtympanic aerator for medium duration of use and made of flexible silicone is presented, its funnel shape preventing stagnation of plugs or allowing their simple removal. The cavity mucosa remains visible and the installation of medication is facilitated. A statistical analysis of results in 159 cases showed that it remained in place for 9 months in children and 7 months in adults on average. A total of 310 conical drains have been inserted since 1981, without any incident because they are extremely well tolerated. PMID- 4039908 TI - Biochemical theories of schizophrenia and depression. AB - Schizophrenia and endogenous depression are now considered to have a genetic biochemical basis. Many theories have been proposed to explain their pathogenesis. The dopamine hypothesis, despite many short-comings, has been the most fruitful of the various hypotheses to explain schizophrenia. The amine hypothesis of depression has had a long life and has been of considerable heuristic value. Inevitably, these hypotheses will be refined or replaced, for this is the nature of science. What is most important is that the scientific method has been brought to bear on psychiatric problems. PMID- 4039909 TI - Evidence of an active glucose uptake in Rhizobium meliloti. AB - Rhizobium meliloti M5N1 showed immediate uptake of glucose. Glucose accumulation was a saturable function of the glucose concentration, and km and Vmax values for uptake were determined. The glucose uptake system was found to be proteic with a turnover of about 6 h. This system was observed to be an active ATP-dependent process, since it was severely inhibited by uncouplers. Glucose analogues and others hexoses had some inhibitory effects on glucose uptake, but not polyols and lactose. PMID- 4039910 TI - Paraplegia resulting from rupture of previously asymptomatic intramedullary hemangioblastoma during coitus. PMID- 4039911 TI - [Effect of ethyl alcohol on bile production and lipid peroxidation in tetracycline-induced liver lesions]. AB - The experiments with male albino rats showed that in toxic doses tetracycline induced affections of the liver evident from activation of transferases and alkaline phosphatases in the blood serum, inhibition of bile secretion, synthesis and secretion of bile acids and excretion of bilirubin and cholesterol with the bile. Moreover, the content of the products of lipid peroxidation in liver homogenates increased. Acute intoxication with ethyl alcohol also induced hepatic disorders. However, they were less pronounced. The intoxication was accompanied by inhibition of cholopoiesis associated with increasing free radical oxidation of lipids. On combined use of tetracycline and ethyl alcohol no potentiation or summation of their hepatotoxicity was observed. PMID- 4039913 TI - Ultrastructure in septa in Blastobotrys and Sporothrix. AB - Transmission electron micrographs of septa in Blastobotrys species invariably showed central micropores. Septa of species of Sporothrix, however, exhibited three types of pores: micropores which were central if single, or scattered; central simple pores with Woronin bodies; dolipores. The results confirm the heterogeneity of the genus Sporothrix. PMID- 4039912 TI - Carbohydrate patterns and taxonomy of Sporothrix and Blastobotrys. AB - Within the hyphomycete genus Sporothrix Hektoen & Perkins three distinct groups are recognized on the basis of carbohydrate patterns. In the first group, and in Blastobotrys Klopotek, mannose is predominant while xylose and rhamnose are absent; this suggests a relationship with the Ascoideaceae. A second group, comprising anamorphs of Ophiostomataceae, is characterized by the presence of rhamnose. A third group is characterized by the presence of xylose, indicating a basidiomycete affinity. Three sections are erected to accommodate these groups. PMID- 4039914 TI - Antimycin A- and hydroxamate-insensitive respiration in yeasts. AB - In this paper evidence is presented for the mitochondrial localization of the antimycin A (AA) + salicylhydroxamate (SHAM)-insensitive respiration of the yeasts Kluyveromyces lactis, Endomycopsis capsularis and Hansenula saturnus. Such a respiration, which can be sustained by NADH and NADPH but not by succinate, is inhibited by high concentrations of azide. AA + SHAM-insensitive respiration is not phosphorylating and its postulated physiological role is to oxidize NADH. PMID- 4039915 TI - Blastobotrys, Sporothrix and Trichosporiella: generic delimitation, new species, and a Stephanoascus teleomorph. AB - The morphological and physiological characters of the species of Blastobotrys, and of a number of similar species of Sporothrix, Trichosporiella and Candida were studied. Blastobotrys is defined as having mother cells (primary conidia) which form distinct, secondary conidia. Sporothrix has non-catenulate conidia, or the conidia are catenulate without marked differentiation of conidia of first and second order. Trichosporiella is delimited from Candida by a stronger coherence between hyphal cells, arthroconidia being absent. Four new Blastobotrys species are described, and two unnamed species; two new combinations are proposed in Trichosporiella. Related species in other genera are briefly discussed. A new Stephanoascus teleomorph is described in two strains originally identified as Sp. fungorum. Two diagnostic keys to the described taxa, using either morphological or physiological characters, are given. PMID- 4039916 TI - Characteristics of protein tyrosine kinase activities of Y-79 retinoblastoma cells and retina. AB - Protein tyrosine kinase activities were determined in retina and Y-79 retinoblastoma cells. Kinase activity was associated with particulate subcellular fractions. Specific activities were similar in both retina and Y-79 cells; apparent Km values for ATP and casein were also similar. Retinoblastoma-derived growth factor stimulated endogenous protein tyrosine phosphorylation in Y-79 cells significantly more than in retina. Differences in protein tyrosine phosphorylation between retina and Y-79 retinoblastoma appear to be due to differences in regulation of the activity by the growth factor or differences in the endogenous protein substrates present in the Y-79 cells. PMID- 4039917 TI - [The effect of methotrexate on intracellular nucleotide pools]. AB - In a previous study, we showed that methotrexate (MTX) enhanced the intracellular production of ara-CTP. The study described in the present paper has elucidated the mechanism of this MTX-enhanced ara-CTP production, which occurs as a result of MTX reducing the intracellular dCTP pool, and the decreased dCTP pool then allowing activation of deoxycytidine Kinase. One of the mechanisms of synergistic interaction between 1-beta-D-arabinofuranosylcytosine (ara-C) and MTX might therefore be the stimulated phosphorylation of ara-C with MTX-activated deoxy cytidine kinase. Using high-pressure liquid chromatography, the sequential changes occurring in the acid-soluble intracellular nucleotide pools of L1210 mouse leukemic cells were analysed after treatment with MTX (12mg/kg). At 3 hr after treatment with MTX a reduction of the dTTP pool to 46% of the control level was observed. The dCTP pool was also reduced to 36% of the control level after treatment with MTX. The levels of the dATP and dGTP pools were not significantly changed, at least during the observation period. Pyrimidine ribonucleotide pools were almost unchanged at 3 hr, but in the sequential changes observed in purine ribonucleotide pools after treatment with MTX, both diphosphate and triphosphate pools were seen to be on the decline, the reduction of triphosphate pools being especially marked. A decline in ATP and GPT to 24-30% of control levels was observed at 3 hr after treatment with MTX. PMID- 4039918 TI - [Corticosteroid as an anti-emetic agent in cancer chemotherapy with cis-diammine dichloroplatinum (II)]. AB - The anti-emetic effect of corticosteroid during cancer chemotherapy with cis diamminedichloroplatinum (II) (CDDP) is analyzed retrospectively. From November 1981 to April 1984, 23 of 50 patients receiving CDDP were given corticosteroid as an anti-emetic. Corticosteroids, methylprednisolone (80-500 mg/day) or hydrocortisone (200-480 mg/day), were administered intravenously for 1 to 3 doses. Including 4 patients who had no symptoms, 60% of patients were free from nausea and vomiting. The incidence of gastrointestinal symptoms was significantly lower than that in patients who were not given corticosteroid. Corticosteroid reduced gastrointestinal symptoms in 2 of 3 patients who had prior CDDP treatment. There were no remarkable adverse reactions except acne in 2 patients. A further controlled study is needed to determine the appropriate dose and modality of administration of corticosteroid. PMID- 4039919 TI - [Combination chemotherapy with cisplatin, ifosfamide and adriamycin in patients with advanced transitional cell carcinoma of the urinary tract]. AB - A combined chemotherapy with cisplatin, ifosfamide and adriamycin (CIA therapy) was performed in 20 patients with advanced transitional cell carcinoma of the urinary tract. Adriamycin 30mg/m2 and ifosfamide 1.5g/m2 were administered on day 1 and cisplatin 50 mg/m2 on day 2, which was repeated at intervals of 3 weeks, in principle. According to Koyama and Saito's response criteria, complete response (CR), partial response (PR) and minor response (MR) were obtained in 1, 4 and 5 cases, respectively; CR+PR+MR in 10 cases out of 18 evaluable cases (56%). The duration of response was 2 to 14 months (median; 4 months) in the cases with CR and PR. The survival time of the responders ranged from 3 to 23 months (median; 11 months), being significantly longer than that of the non-responders (p less than 0.05, Generalized Wilcoxon test). Adverse reactions observed were of a slight or moderate degree, with only a few cases of damage to renal function. PMID- 4039920 TI - Urine albumin to creatinine ratio-response to exercise in diabetes. AB - Albuminuria was studied in 40 diabetic children before and after a standardised exercise test, and also in 21 normal children; the results are expressed as geometric mean (95% range) of urine albumin:urine creatinine ratio (mg/mg). There was no significant difference between the mean resting albumin:creatinine ratio in the two groups, or between these ratios before and after exercise in the normal children. In the diabetic children, however, the mean urine albumin:creatinine ratio after exercise was significantly higher than both the value before exercise and the postexercise value of the normal children, with 10 of 40 diabetic children showing a value after exercise greater than the 95% range of the geometric mean of the control group. The diabetic children were also studied by random urine albumin:creatinine ratios and split (erect:supine) 24 hour urine collection; none was abnormal. PMID- 4039921 TI - Alcohol and the fetus. PMID- 4039922 TI - [Rearing of female cattle twins using complete feed pellets in comparison to straw pellets plus concentrate mixture. 1. Weight gain performance and feed expenditure as well as rumen fermentation conditions during the 4th-12th months of life]. AB - The investigations with young female cattle (twin cattle, n = 30) the applicability of straw as sole roughage after the end of the suckling period was tested. Completely (I) and partly (II) pelleted rations of dried feed with a straw component of 65% each in the total rations were used. Feed intake, development of body weight, feed expenditure as well as indexes of rumen fermentation and of the concentration of some metabolism parameters in the blood serum were measured. In the complete test period (between 5th and 12th months of life, 243 days) there were not any significant differences between the groups in all registrations. Average daily weight gains of 570 g were achieved with an overall high dry matter (2.6 kg/100 kg live weight) and roughage (straw) intake (1.6 kg dry matter/100 kg live weight). The standard expenditure of energy and protein given for the stage of development was differentiatedly undercut. The energy expenditure being below the standard (ca. 10%), the total energy expenditure (kEFUcattle) was by 20 (II) and 25% (I) below standard expenditure. Energy expenditure aimed at weight gain reached very satisfactory values with 3.68 (I) and 3.79 kEFUcattle/kg weight gain (II). Protein expenditure fell short of the standard for the development stage by 14 (II) and 20% (I) resp. All parameters ascertained of the rumen and intermediate metabolism were in the physiologic standard range, as is characteristic of feeding regimes with a relatively high quota of roughage. PMID- 4039923 TI - Enbucrilate as cartilage adhesive in augmentation rhinoplasty. AB - Enbucrilate (Histoacryl) as a cartilage adhesive in augmentation rhinoplasty was used in 39 cases. The unique properties of this tissue adhesive enhances the ability to augment the nose during cosmetic and reconstructive rhinoplasty. Enbucrilate interacts superbly well with local tissues, causing no systemic or local untoward effects. Its main attribute stems from its ability to bond cartilage instantaneously and with great reliability, which allows for intricate fabrication of cartilage implant components. Five subcategories of dorsal, tip, and columella augmentation are presented with their technical details outlined. The aesthetic and functional results in 39 cases were deemed excellent, safe, and effective. PMID- 4039924 TI - Clinical and haematological features of haemangiosarcoma in dogs. AB - Canine haemangiosarcoma was studied retrospectively in 31 cases recorded among 2,871 dogs presented for necropsy (1.08%). The German Shepherd breed was more frequently represented than other breeds. Affected dogs were older than 5 years (mean 9.1 years). Nineteen were males. Presenting signs often included episodic lethargy and weakness, with depression, anorexia and mucosal pallor. Spleen and lungs were the most frequently affected sites. Haematological findings in 9 dogs with splenic or hepatic haemangiosarcoma included a mild to moderate normochromic anaemia, neutrophilia, thrombocytopaenia, poikilocytosis and increased target cells. Acanthocytes occurred in 90% of cases, schizocytes in 80% and keratocytes and metarubyricytes in 70%. Fibrin split products were increased in 2 of the 3 cases in which they were measured. The changes in erythrocyte morphology are considered to be useful diagnostic features of canine haemangiosarcoma. PMID- 4039925 TI - Dipetalonema reconditum in dogs with microfilaraemia. PMID- 4039926 TI - Investigations into Crofton weed (Eupatorium adenophorum) toxicity in horses. PMID- 4039927 TI - Septal lesions and biting attacks in rats bidirectionally selected for emotionality. AB - Twenty-nine colonies composed of one female and two male rats of high or low emotional strain were established. A dominant male of each colony was identified based on its attacks on an intruder rat. It was found that dominant males of the low emotional strain colonies were significantly more aggressive than those of the high emotional strain. Septal lesions or sham operations were given to dominant males of both strain colonies. Intruder tests were followed and several aggressive behaviors were measured by VTR observation. Biting attacks of the high emotional strain decreased for 10 days after septal latencies were shortened by septal lesions. Lesions X Strain interaction was significant. These results suggest that septal lesion effects on biting attacks are influenced by artificial genetic operations. PMID- 4039928 TI - Effects of vagino-cervical stimulation upon sociosexual behaviors in female rats. AB - The role of vagino-cervical stimulation in the control of feminine copulatory behavior in the behaviorally estrous rat was examined in a complex environment that allowed the test female to pace her contacts with sexually active males, sexually passive males and ovariectomized females. Manipulations of vagino cervical stimulation by administration of a topical anesthetic or by probing with a glass rod, immediately before testing in the complex environment, did not significantly alter any aspect of behavior in behaviorally estrous females. Transection of the pelvic nerve increased the number of intromissions and ejaculations that the females received and increased the amount of time that the females spent with the sexually active males. The present results implicate the pelvic nerve in the modulation of motivation for coital contacts in the female rat. PMID- 4039930 TI - Weight-reducing diets. AB - No single diet exists for the treatment of obesity. On the contrary, a variety of diet regimes should be taken in consideration in this disease. Even a normoenergic diet can produce the desired reduction of overweight if it is combined with physical exercise. A moderately reducing diet has a number of advantages over the very low-energic ones, as it leads to the preservation of the lean body mass, especially when the diet is accompanied by a regime of high physical activity. In obesity and other metabolic disorders, it is convenient to include in the diet low-energy foods rich in fiber with a possibly specific hypolipidemic effect, such as soy dishes, pectin-enriched dishes, fruit purees and juices, skimmed milk yogurt, wheat bran bisquits, and others. PMID- 4039929 TI - Ischemia aggravating effects of platelet-activating factor in acute myocardial ischemia. AB - The effect of platelet-activating factor (PAF) was studied during the acute phase of myocardial ischemia in cats. PAF infusion (0.75 micrograms/kg/h for 4.5h) in anesthetized, open-chest cat decreased arterial blood pressure, but did not influence heart rate or biochemical indices of cell integrity. The same dose of PAF, however, started 30 min after coronary ligation, resulted in a significantly higher elevation of plasma creatine phosphokinase (CK) activity and a reduced CK content in the region of the ischemic myocardium. Treatment with the thromboxane A2 synthetase inhibitor, CGS-13080, significantly attenuated the PAF-aggravated ischemic cellular damage. These experiments suggest that hypoxia-generated PAF may contribute to the aggravation of myocardial ischemia, part of which appears to be due to PAF-induced release of thromboxane A2. PMID- 4039931 TI - Tumor promoter-stimulated translocation of glucose transport system in mouse embryo fibroblast Swiss 3T3 cell. AB - Assay for D-glucose-inhibitable 3H-cytochalasin B-binding was carried out to elucidate the action mechanism of the tumor promoter-induced enhancement of glucose transport activity in Swiss 3T3 cells. Incubation of the cells with 12-0 tetradecanoylphorbol-13-acetate (TPA) increased the amount of D-glucose inhibitable cytochalasin B-binding sites in plasma membrane from 13.5 to 40.1 pmol/mg protein. On the other hand, TPA treatment resulted in the decrease of binding sites in microsomal membrane from 68.9 to 34.1 pmol/mg protein. The tumor promoter-induced translocation of hexose transport system from microsomal membrane to plasma membrane was inhibited by the treatment with 2,4-dinitrophenol before the addition of TPA but was not affected by the treatment with cycloheximide. By removal of the promoter from its receptor, the stimulatory effect of the promoter on the translocation of hexose transport system was decreased. The analysis by electrophoresis demonstrated that among the affinity labeled hexose transporter components of Mr 48,000 and Mr 55,000, the former was responsible for the TPA-induced increase in hexose transport activity in plasma membrane. PMID- 4039932 TI - Control of sugar transport in human fibroblasts independent of glucose metabolism or carrier-substrate interaction. AB - Transport regulation by different metabolizable and nonmetabolizable sugars was studied in human fibroblasts. Sugars were classed as glucose-like (D-mannose, 3-0 methyl-D-glucose, thio-D-glucose, and D-allose) and starvation-like (D-galactose, D-fructose, L-glucose, D-xylose, 6-deoxy-D-glucose and 2-deoxy-D-glucose) based on their competence in curbing glucose starvation enhanced transport. No significant correlation existed between the ability of a sugar to curb hexose transport and the KI of that sugar in inhibiting hexose transport. Independence of the transport curb from glucose metabolism was observed since nonmetabolizable analogs of D-glucose when substituted for D-glucose in the culture medium effected glucose [i.e. 3-0-methyl-D-glucose (3-OMG)] and starvation-like (i.e. 6- and 2-deoxy-D-glucose) effects. The KI of inhibition pf 2-deoxy-D-glucose transport for 3-OMG was 8.5 mM, similar to those obtained for 6-deoxyglucose and 2-deoxyglucose on 2-deoxyglycose transport (7.5 and 3.5 mM, respectively) and on 3-0-methylglucose transport (3.5 and 2.5 mM, respectively). An equimolar mixture of D-glucose and 3-OMG (5.55 mM each) was more effective than 11.1 mM D-glucose or 3-OMG alone in curbing hexose transport or reversing hexose starvation induced increases in transport. The effect of 3-OMG may be independent of glucose metabolism but it is possible that 3-OMG structurally mimics a metabolite of glucose that may interact with intracellular regulators of carrier degradation and or expression. PMID- 4039933 TI - Molecular forms of atrial natriuretic polypeptides in mammalian tissues and plasma. AB - A highly sensitive radioimmunoassay detecting for all the atrial natriuretic polypeptides isolated so far from human and rat (hANPs and rANPs) has been established by using an antiserum raised against alpha-hANP, since the antiserum recognizes the subsequence flanked by two cysteine residues (positions 7 and 23) in alpha-hANP and crossreacts with human as well as rat ANPs. By using the radioimmunoassay combined with gel chromatography or high performance liquid chromatography, it was revealed that ANP immunoreactivity in human atria is composed of alpha-(28 residues), beta-(56 residues: alpha-hANP dimer) and gamma hANP(126 residues) in various ratios. In rat, porcine and bovine atrial tissues, however, gamma-rANP(126 residues) was found to be a major component. In contrast with atrial ANP, plasma ANP was found to be predominantly alpha-form in rat. PMID- 4039934 TI - Requirement of a reactive alpha, beta-unsaturated carbonyl for inhibition of tumor growth and induction of differentiation by "A" series prostaglandins. AB - Prostaglandins of the A series have been reported to inhibit tumor cell growth and induce tumor cell differentiation by a yet unknown mechanism. We propose that these effects are due to the presence of a reactive alpha, beta-unsaturated carbonyl group (delta 10,11) in the cyclopentane ring of the PGA molecule. PGA was effective whereas PGB (sterically hindered alpha, beta-unsaturated carbonyl at delta 8, 12) and PGA conjugated to glutathione were ineffective. 15-Epi-PGA2 was as effective as PGA2 suggesting that the S absolute configuration of the 15 hydroxyl group is not essential. There was no correlation between generation of cAMP and inhibition of cell proliferation or induction of differentiation by various prostaglandins. The data suggest that PGA's and PGA-like compounds inhibit tumor cell growth and induce differentation because of the chemical reactivity of the alpha, beta-unsaturated carbonyl rather than hormonal activity of the prostanoid nucleus. PMID- 4039935 TI - Atrial natriuretic polypeptides (ANP): rat atria store high molecular weight precursor but secrete processed peptides of 25-35 amino acids. AB - A radioimmunoassay was developed for rat atrial natriuretic polypeptides. Using the radioimmunoassay and gel filtration in reducing and dissociating conditions, extracts of rat atria were found to contain mainly a 15000-dalton immunoreactive material, probably corresponding to pronatriodilatin. However, when isolated beating atria were incubated in plasma-free conditions, the secreted immunoreactive material consisted almost exclusively of 2500-3500-dalton peptide(s). These results show that rat atrial cells secrete a low molecular weight natriuretic peptide which is highly active, but store the less active large molecular weight form(s). PMID- 4039936 TI - Diurnal variation of methotrexate transport and accumulation in hepatocytes--a consequence of variations in cellular glutathione. AB - Diurnal variation of the methotrexate (MTX) initial influx and net uptake in isolated rat liver cells was studied in dependence on diurnal variation of cellular glutathione. It was found that the most significant differences concerning the MTX initial transport and accumulation were observed between hepatocytes prepared at 1200 hr when cellular glutathione reached its maximum, and those isolated at 0000 hr when liver glutathione had its minimal concentration. The initial influx of MTX was the biggest in cells isolated at 0000 hr and the smallest in cells prepared at 1200 hr. The Km values in cells with low cellular glutathione (at 1800 and 0000 hr) were about three times smaller than in cells with high glutathione (at 0700 and at 1200 hr), whereas the Vmax value remained unchanged. Titration of external membrane SH groups by [203Hg]p-CMBS revealed a much larger amount of free SH groups on cells having low glutathione level than on those with high glutathione. Despite big initial influx of MTX found in cells with low cellular glutathione, net accumulation of MTX was significantly smaller in these cells as compared with hepatocytes having high glutathione level. In conclusion, the present studies confirmed a statement of the preceding paper on the important role of cellular glutathione played in methotrexate transport and accumulation in rat liver cells. PMID- 4039937 TI - Benzo[a]pyrene metabolism in mouse liver. Association of both 7,8-epoxidation and covalent binding of a metabolite of the 7,8-diol with the Ah locus. AB - The 7,8-epoxidation of benzo[a]pyrene, and the 9,10-epoxidation of benzo[a] pyrene trans-7,8-dihydrodiol coupled with covalent binding of the highly reactive diol-epoxide, are two key P-450-mediated reactions believed to be important in cancer initiation, mutagenesis and teratogenesis. New assays for these two reactions were developed with mouse liver microsomes. These two activities have apparent Km values (approximately 6 microM) similar to that of aryl hydrocarbon hydroxylase activity. Twenty-six individual 3-methylcholanthrene-treated Ahb/Ahd and Ahd/Ahd progeny of the (C57BL/6N)(DBA/2N) F1 X DBA/2N backcross were studied. Both of the newly described activities appear to represent P-450 protein(s) that are responsible for aryl hydrocarbon hydroxylase activity and that are coordinately controlled by the Ahb allele. PMID- 4039938 TI - Effect of dietary clofibrate on epoxide hydrolase activity in tissues of mice. AB - The effects of dietary clofibrate on the epoxide-metabolizing enzymes of mouse liver, kidney, lung and testis were evaluated using trans-stilbene oxide as a selective substrate for the cytosolic epoxide hydrolase, cis-stilbene oxide and benzo[a]pyrene 4,5-oxide as substrates for the microsomal form, and cis-stilbene oxide as a substrate for glutathione S-transferase activity. The hydration of trans-stilbene oxide was greatest in liver followed by kidney greater than lung greater than testis. Its hydrolysis was increased significantly in the cytosolic fraction of liver and kidney of clofibrate-treated mice and in the microsomes from the liver. Isoelectric focusing indicates that the same enzyme is responsible for hydrolysis of trans-stilbene oxide in normal and induced liver and kidney. Clofibrate induced glutathione S-transferase activity on cis-stilbene oxide only in the liver. Hydrolysis of both cis-stilbene oxide and benzo[a]pyrene 4,5-oxide was highest in testis followed by liver greater than lung greater than kidney. Hydration of cis-stilbene oxide was induced significantly in both liver and kidney by clofibrate but that of benzo[a]pyrene 4,5-oxide was induced only in the liver. These and other data based on ratios of hydration of benzo[a]pyrene 4,5-oxide to cis-stilbene oxide in tissues of normal and induced animals indicate that there are one or more novel epoxide hydrolase activities which cannot be accounted for by either the classical cytosolic or microsomal hydrolases. These effects are notable in the microsomes of kidney and especially in the cytosol of testis. PMID- 4039939 TI - Streptozotocin-induced diabetes and hormone sensitivity of adenylate cyclase in rat myocardial sarcolemma, aorta and liver. AB - Adenylate cyclase activity was investigated in myocardial sarcolemma, aorta particulate fractions, and liver plasma membranes from control and 5-day streptozotocin-induced diabetic rats. The basal adenylate cyclase activity was increased in heart sarcolemma from diabetic rats, whereas the extent of stimulation by glucagon, dopamine, isoproterenol, epinephrine, sodium fluoride and forskolin was decreased markedly. The decreased responsiveness was associated with a decrease in Vmax but not in the activation constant. In contrast, GTP stimulated adenylate cyclase in control and diabetic myocardial sarcolemma to the same extent. In addition, the basal adenylate cyclase activity was not altered significantly in aorta particulate fraction of liver plasma membranes from diabetic rats, but the stimulation of adenylate cyclase by catecholamines and forskolin (in the case of aorta) and by adenosine, glucagon, NaF and forskolin (in the case of liver) was diminished markedly. These data suggest that, in streptozotocin-induced diabetes, the responsiveness of adenylate cyclase to various hormones and agents (fluoride and forskolin) which act through receptor independent mechanisms is decreased. PMID- 4039940 TI - Silymarin protection against hepatic lipid peroxidation induced by acute ethanol intoxication in the rat. PMID- 4039941 TI - [Evaluation of gentamicin as a prophylactic antibiotic in exchange transfusion]. PMID- 4039942 TI - Purification and characterization of four isolectins of mushroom (Agaricus bisporus). AB - Four lectins were purified from a mushroom (Agaricus bisporus) by ammonium sulfate fractionation, anion-exchange chromatography, affinity chromatography on bovine submaxillary mucin-Sepharose 4B and preparative isoelectric focusing. They were designated as ABA-I (pI 6.70), II (pI 5.98), III (pI 5.69) and IV (pI 5.53). Polyacrylamide gel electrophoresis of each lectin in the presence of sodium dodecyl sulfate gave a single band with an apparent molecular mass of 16 000 Da. Sedimentation equilibrium analysis suggested that each lectin is a tetramer of subunits. The four lectins were found to have quite similar carbohydrate-binding specificities. The hemagglutination activities of the lectins were effectively inhibited by bovine and porcine submaxillary mucins (BSM and PSM), and NH2 terminal glyco-octapeptides obtained by cyanogen bromide cleavage of human erythrocyte glycophorin A. In addition, desialylated PSM-glycopeptides were more potent inhibitors than untreated PSM-glycopeptides. Among monosaccharides and their glycosides, only methyl N-acetyl-alpha-galactosaminide inhibited lectin binding at a high concentration, but a synthetic oligosaccharide, O-beta galactopyranosyl-(1----3)-O-(2-acetamido-2-deoxy-alpha-D- galactopyranosyl)-N tosyl-L-serine, was a strong inhibitor. PMID- 4039943 TI - Refractory idiopathic thrombocytopenic purpura (ITP) treated with cyclosporine. PMID- 4039944 TI - Enquiry into perinatal death. PMID- 4039945 TI - Why are stillbirth and neonatal mortality rates continuing to fall? AB - The Office of Population Censuses and Surveys are producing new annual tabulations including one on population birthweight distribution, and birthweight/cause-specific perinatal, neonatal and infant mortality rates. With these data it will be easier to distinguish between falls in mortality rates due to primary prevention of the causes, and those due to secondary prevention as a result of improved medical technology. Examples are given of the use of such data. PMID- 4039946 TI - Mydriatic drugs for diabetic patients. AB - A comparative study in healthy subjects and diabetic patients of the mydriatic response to topical tropicamide 0.5% with and without added phenylephrine 10% is reported. The findings indicate that diabetic pupils respond relatively poorly to tropicamide alone but adequately and completely to the drug combination. The pupils of diabetic patients whose eyes had previously received laser treatment dilated less than those from untreated eyes by a small but significant extent. This combination of drugs is recommended for all diabetic patients to provide an adequate mydriasis with a minimum of postclinic accommodative paralysis. PMID- 4039947 TI - Fast and slow artificial diurnal rhythms (light-darkness-light) and the rate of progression of retinal degeneration in dystrophic RCS rats. An electroretinographic study. AB - The RCS rat strain is characterized by a hereditary progressive degeneration of retina and pigment epithelium. The possible influence of varying artificial diurnal rhythms on the rate of progression of the degeneration was investigated with electroretinography (ERG). Light intensity of the 'day'-periods and the total light exposure were constant in two groups of RCS rats subjected to 2 h light/2 h darkness and to 24 h light/24 h darkness periods respectively. No difference in the rate of degeneration as mirrored by the ERG was seen between the two groups. The ERGs were unrecordable after 7-8 weeks, and the experiments started at birth. No changes in the ERG of controls, genetically identical with the RCS strain except for the retinal dystrophy gene, were seen when they were subjected to the two diurnal rhythms. The results lessen the probability that careful long-term patching of an eye in patients with retinitis pigmentosa or other related hereditary degenerative diseases (in order to diminish the influence of diurnal illumination changes leading to shedding of receptor outer segments) will halt or modify the progression of the disease in man. PMID- 4039948 TI - Vesicle release from rat red cell ghosts and increased association of cell membrane proteins with cytoskeletons induced by cadmium. AB - When rat red cell ghosts were incubated with 0.1-0.5 mM CdCl2 in 10 mM Tris-HCl (pH 7.4) at 37 degrees C for 30 min, they became irregular in shape and released small vesicles. The release of vesicles was dependent on the incubation temperature and Cd2+ concentration. The maximum release occurred at 37 degrees C in the presence of 0.2 mM Cd2+. The protein composition of Cd2+-induced vesicles was similar to that of the vesicles released from ATP-depleted red cells. Upon incubation with 0.1-0.2 mM Cd2+, more than 90% of the Cd2+ added to the incubation buffer was recovered in ghosts and 15-20% of the ghost Cd2+ was located on the cytoskeletons prepared by washing ghosts with 0.5% Triton X-100 solution containing 0.1 M KCl and 10 mM Tris-HCl (pH 7.4). Moreover, the cytoskeletons prepared from Cd2+-treated ghosts markedly contained cell membrane proteins, bands 2.1, 3, 4.2 and 4.5, and glycophorins. The association of bands 3 and 4.2 with cytoskeletons increased with increasing concentrations of Cd2+ added to the incubation buffer and saturated at 0.2 mM Cd2+. The solubilization of cytoskeletal proteins, bands 1, 2 and 5, from ghosts at low ionic strength was almost completely suppressed by preincubation of ghosts with 0.1 mM Cd2+. HgCl2, PbCl2 and ZnCl2 at 0.2 mM each also produced an increased association of cell membrane proteins with cytoskeletons, whereas CaCl2 and MgCl2 did not. PMID- 4039949 TI - Bile salt damage of egg phosphatidylcholine liposomes. AB - Physiochemical damage of egg phosphatidylcholine liposomes, caused by the salts of three bile acids, chenodeoxycholic acid, ursodeoxycholic acid, and cholic acid, has been investigated. Of the three bile salts, that of chenodeoxycholic acid was the most destructive, and the effect of the damage was examined by monitoring the induced 6-carboxyfluorescein release from the liposomes. For all three of the bile salts and under the experimental conditions, the minimum (effective) concentrations causing the 6-carboxyfluorescein release were below their critical micelle concentrations. In the case of the salt of chenodeoxycholic acid, the presence of cholesterol in the liposomal bilayers did not show any significant effect on the induced 6-carboxyfluorescein release, while, for the salts of ursodeoxycholic acid and cholic acid, the presence of cholesterol tended to depress the release. Permeation of bile salts into the membranes of liposomal bilayers made these membranes more fluid, and this fluidity was monitored by measuring the change in fluorescence polarization using 1,6-diphenylhexatriene entrapped in the liposomes. Coating the liposomes with polysaccharides, to make them more hydrophobic, led to their easier lysis by the bile salts. PMID- 4039951 TI - Magnesium deficiency psychosis induced by cancer chemotherapy. PMID- 4039950 TI - Dopaminergic supersensitivity follows ferric chloride-induced limbic seizures. AB - Injection of ferric chloride (FC) into the left amygdala of rats produced limbic seizures that lasted at least 3 weeks. In addition, FC-injected animals demonstrated motor impairment, decreased protesting vocalizations, and spontaneous stereotypies during a behavioral examination. An increase in apomorphine-induced stereotypies was also noted, and weekly administration of apomorphine for 3 weeks potentiated the increase in stereotypies produced by FC injection. These behavioral changes were associated with changes in postsynaptic dopamine D2 receptors. In animals injected only with FC, an increase in the [3H] spiperone Bmax in the left nucleus accumbens and an increase in Kd in the right nucleus accumbens were noted. In FC-injected animals challenged weekly with apomorphine for 3 weeks, increases in the [3H]-spiperone Bmax in both amygdalae, the left nucleus accumbens, and the right nucleus caudatus and increases in Kd in the left amygdala and right nucleus accumbens were noted. Severance of the anterior commissure at the time of FC injection reversed most of these changes in behavior and dopamine receptor binding. Possible mechanisms for these changes are discussed, as well as the implications of these results for research on limbic dysfunction and psychopathology. PMID- 4039952 TI - Fertility control in the bitch by active immunization with porcine zonae pellucidae: use of different adjuvants and patterns of estradiol and progesterone levels in estrous cycles. AB - To determine the changes in patterns of 17 beta-estradiol and progesterone levels underlying abnormal cycles in bitches immunized with solubilized crude porcine zonae pellucidae (cPZP), to attempt to circumvent these problems by immunizing with a purified zona fraction (pPZP), and to test the effectiveness of different adjuvants, bitches were immunized with cPZP or pPZP 2-6 times with no adjuvant, Freund's adjuvant, alum adjuvant, or the adjuvant CP-20,961. The bitch immunized without adjuvant had a low titer with a normal cycle and fertility. Immunization with cPZP and adjuvant produced moderate to high titers of antizona antibodies and infertility. Bitches with high titers experienced abnormal estrous cycles. Estradiol rose during proestrus, but instead of falling sharply in early estrus as in controls, it remained elevated. Progesterone did not rise. The moderate titered bitches had normal cycles and steroid patterns. Bitches immunized with pPZP had moderate titers. Cycles were normal after 3 injections, but after 6 injections one bitch had an abnormal cycle. One pPZP-immunized bitch remained fertile but the others were infertile. Alum was the mildest adjuvant, causing no injection site lesions, but the highest titers occurred with Freund's and CP 20,961 adjuvants. All three adjuvants induced titers sufficient to inhibit fertility. Infertility in bitches immunized with PZP may be due to prevention of zona penetration, because their antisera inhibited zona penetration of oocytes by spermatozoa in vitro. However, alterations in ovarian function preventing ovulation and luteinization could be involved in high-titered bitches. PMID- 4039953 TI - The proestrous surge of prolactin enhances sexual receptivity in the rat. AB - The influence of the proestrous surge of prolactin (Prl) on expression of feminine sexual behavior (lordosis) has been investigated. In the first experiment, proestrous rats were treated with a dopamine agonist, bromocriptine (CB-154; 100 micrograms at 1200, 1300, and 1600 h), which blocked the proestrous surge of Prl without affecting the preovulatory surge of luteinizing hormone. Such animals displayed depressed lordosis quotients (LQs) when compared to control animals at 2000 h on proestrus. However, in CB-154-treated animals given ovine Prl (10 I.U.) at 1400 h on proestrus, LQs were restored to control levels. Ovariectomized (OVX) rats primed with estradiol benzoate (EB; 2 micrograms for 2 days) produced surges of Prl that were similar in timing to those of proestrous. Once again, CB-154 treatment blocked this Prl surge and significantly depressed the LQ, whereas replacement with ovine Prl returned the LQ to control values. These results suggest that the Prl surge facilitates the expression of lordosis. Ovariectomized/adrenalectomized (ADX) and OVX/sham ADX rats were treated with EB (2 micrograms for 2 days) and tested for lordosis on Day 3. Adrenalectomized rats responded with lower levels of lordosis than did sham controls. Administration of progesterone (P4) to ADX rats on Day 3 enhanced the LQ compared to sham ADX values. CB-154 was ineffective in reversing the enhanced LQ, indicating that Prl may be acting through stimulation of adrenal progestins. These data taken together suggest that the proestrous surge of Prl contributes to the normal expression of feminine sexual behavior on proestrus. PMID- 4039954 TI - Coital stimuli controlling luteinizing hormone secretion and ovulation in the female ferret. AB - A series of experiments focused on the masculine coital behaviors controlling pituitary luteinizing hormone (LH) secretion and reflex ovulation in the estrous female ferret. An initial experiment investigated which coital stimuli from the male are required to induce ovulation. It was found that corpus luteum formation, which served as an index of ovulation, occurred in estrous female ferrets only if the male achieved a penile intromission. Neck gripping, mounting, and pelvic thrusting behavior without intromission by the male failed to induce ovulation. A second experiment investigated the timing and magnitude of the coitus-induced LH surge associated with ovulation. Blood was obtained via jugular catheters from estrous females in various mating situations. Plasma LH concentrations were measured by a heterologous radioimmunoassay that was validated for use in the ferret. A significant surge in plasma LH occurred only when an intromission was achieved by the stud male. Plasma LH was significantly elevated 2.0 h after the introduction of the male, peak values were reached 6.0 h later, and this elevation lasted on average 5.7 hours (5/5 females). No LH rise occurred in 2/2 female ferrets in which only neck gripping, mounting, and pelvic thrusting, but no intromission, were allowed to occur. The ferret mating pattern and the resultant LH response differ from those seen in three other induced ovulators (cat, vole, and rabbit) in which the male's intromission latency and duration are much shorter than in the ferret, and in which a distinctive peak in plasma LH often occurs within 1 h after mating. PMID- 4039955 TI - Comparison of granulosa cell proliferation in small follicles of hypophysectomized, prepubertal, and mature rats. AB - The factors that control the rate of granulosa cell proliferation during follicular development are unknown. The object of this study was to test the hypothesis that growth rates of small and medium follicles may be modulated by cyclic alterations in endogenous hormone concentrations. Follicular growth in adult cycling rats was compared with hypophysectomized rats, untreated prepubertal rats, and prepubertal rats treated with exogenous gonadotropins. Cell kinetics was studied using a metaphase arrest technique and by long-term infusion of [3H]thymidine. Many follicles of hypophysectomized rats showed evidence of continued cell proliferation despite the absence of gonadotropins. In hypophysectomized rats, follicular growth was able to proceed to the size of the largest healthy non-preovulatory follicles in the proestrous rat ovary. Follicular growth in prepubertal rats progressed little beyond this same size range. Granulosa cell proliferation rates differed in immature rats and cycling rats. Granulosa cells in small follicles (80-180 cells in the largest cross section) of cycling rats grew slowly. However, granulosa cells in small follicles of immature rats were among the fastest growing in the ovary. These results suggest that, although gonadotropins are not absolutely required to maintain granulosa cell proliferation in small follicles, the rate at which these follicles grow varies under different hormonal conditions. PMID- 4039956 TI - [Microvascular permeability in rats susceptible and not susceptible to the development of experimental alcoholism]. AB - Using the fluorescence technique it has been shown that rats predisposed to the development of experimental alcoholism have a higher permeability of mesenterial microvessels as compared to non-predisposed animals. The role of enzymes and the endothelium in the mechanisms of permeability is discussed. PMID- 4039957 TI - [Effect of the destruction of the brain serotoninergic system on the alcohol consumption by rats in the early periods of experimental alcoholism]. AB - Albino noninbred rats were divided into groups, according to the duration of alcoholic anesthesia (4.5 g/kg i.p.), of predisposed (195.6 min) and non predisposed (69.1 min) to voluntary intake of alcohol. Another group included animals screened for 21 days according to the level of intake of 15% ethanol under the conditions of free choice between alcohol and water (6.15 and 2.62 g/kg pure ethanol per day, respectively). The animals were subjected to electro coagulation of the dorsal or magnus raphe nucleus or were injected with 5,6 dihydroxytryptamine--DNT (75 micrograms/microliters) into the ventricles of the brain. It was established that in rats non-predisposed to alcohol intake, the destruction of the raphe nuclei, of the dorsal in particular, or injection of DOT to animals with a weak alcoholic motivation produces a dramatic increase in alcohol intake. In alcohol intake predisposed rats and in animals with a high level of alcohol use, analogous exposures do not bring about any significant differences in alcohol intake. The data obtained indicate that the reduced serotonin content in the brain is associated with an increase in the level of alcoholic motivation. PMID- 4039958 TI - The transport of 125I-labeled human high molecular weight urokinase across the intestinal tract in a dog model with stimulation of synthesis and/or release of plasminogen activators. AB - In an attempt to elucidate the mechanism of fibrinolytic enhancement by orally administered urokinase, studies on the intestinal transport of urokinase were carried out, using 125I-labeled human high mol wt urokinase, administered intraduodenally in the experimental dog model with a saphenous vein thrombus. Using the plasma sample obtained from blood 45 minutes after intraduodenal administration of the urokinase, protein fractions were isolated by a sequential two-step affinity chromatography method, first with [N alpha-(epsilon aminocaproyl)-DL-homoarginine hexylester]-Sepharose followed by a specific anti human low mol wt urokinase rabbit IgG-Sepharose (adsorbed-eluted and unadsorbed). Each of the isolated protein fractions was further purified by gel filtration on Sephacryl S-300. The proteins isolated by the two-step affinity chromatography method were transported human urokinase with radioactivity in the adsorbed-eluted fraction, and newly synthesized and/or released dog plasminogen activators, probably urokinase-type and tissue-activator type, without radioactivity. In an antibody quenching assay, dog urokinase and the immuno-affinity unadsorbed fraction were not neutralized, but the immuno-affinity adsorbed-eluted fraction was completely neutralized by the specific anti-urokinase IgG antibody. Proteins isolated from control plasma (after administration of saline) by the two-step affinity chromatography method in the unadsorbed fraction had negligible amounts of activator activity. In these studies, we were able to show that synthesis of plasminogen activators was stimulated, with the activators being released, from either the liver or the vascular endothelium. Also we showed that urokinase is transported across the intestinal tract in the dog model. PMID- 4039959 TI - Ventral rhizotomy enhances regeneration of uninjured sensory neurons. AB - Uninjured sensory neurons show metabolic and morphologic changes, as well as enhanced regeneration, when exposed to adjacent degenerating ventral root fibers. The release of a neurotrophic factor from the degenerating nerve fibers may be responsible for 'priming' the uninjured neuron and thereby enhancing its response to injury. PMID- 4039960 TI - Changes in physostigmine-induced hippocampal seizures during ethanol withdrawal. AB - Hippocampal cholinergic neurons are sensitive to acute ethanol administration, and specific alterations are seen in the functioning of these neurons following chronic ethanol. The present study examined the effects of chronic ethanol exposure and withdrawal on the sensitivity of the hippocampus to local injection of physostigmine, an inhibitor of acetylcholine metabolism. While intrahippocampal physostigmine elicited hippocampal seizure activity in 80% of the animals tested during withdrawal from chronic exposure to low levels of ethanol, seizure activity was elicited in only 30% of ethanol-naive subjects. These results suggest that chronic ethanol exposure may increase the sensitivity of hippocampal neurons to cholinergic stimulation, and that some of the symptoms of ethanol withdrawal may be related to this change. PMID- 4039961 TI - Effect of copper on the binding and electrophysiological actions of cyclohexyladenosine. AB - Since copper ions irreversibly reduce the binding of cyclohexyladenosine (CHA) to rat brain membranes and copper levels are elevated in the brains of seizure-prone mice, the binding of CHA was compared in seizure-prone DBA/2 and control C57 mice. No strain difference was detected in the binding of CHA or the reduction of that binding by copper, although copper was more potent than in rats (IC50 12 microM). In rat hippocampal slices copper did not diminish the inhibitory effects of adenosine or CHA. The results suggest that the seizure sensitivity of DBA/2 mice is not due to an effect of copper on purine receptors and that the copper binding domain of purine receptors is inaccessible to extracellular copper. PMID- 4039962 TI - Topographically organized midbrain modulation of predatory and defensive aggression in the cat. AB - Hypothalamic sites from which quiet biting attack and affective defense were elicited, were concurrently stimulated with others in the midbrain from which modulation of these behaviors was attempted. Stimulation of medial and lateral aspects of the tegmentum differentially modulated quiet biting attack and affective defense behavior. Facilitation of quiet attack and suppression of affective defense resulted from stimulation of the lateral tegmentum, while suppression of quiet attack and facilitation of affective defense followed stimulation of its medial aspect. PMID- 4039963 TI - Reduced metabolic response of the rat brain to haloperidol after chronic treatment. AB - Local cerebral glucose utilization (LCGU) was determined, using the quantitative autoradiographic [14C]2-deoxy-D-glucose technique, in 47 brain regions of awake rats, after acute and chronic haloperidol (HAL) administration (1 mg/kg or 1 mg/kg/day). LCGU was reduced in fewer regions after chronic HAL (19%) than after acute HAL (72%); the average reduction for all regions was smaller (8% and 25%, respectively). The reduced metabolic effect of chronic HAL is not due to a lower brain concentration of the drug, since similar effects on LCGU were found in rats which received an acute i.p. injection of HAL (as in the acutely treated animals) after chronic administration of HAL for 3 weeks. Furthermore, continuous infusion of HAL for 3 weeks or 1 day resulted in similar tolerance to the metabolic effect of HAL. Tolerance was not observed in the mesocortical dopamine (DA) system. The present findings show that tolerance develops to the effect of HAL on cerebral metabolism, even after 1 day of HAL treatment. Lack of tolerance in the mesocortical pathway may implicate this system in the neuroleptic effect of chronic HAL. PMID- 4039964 TI - Plasminogen activator is a mitogen for astrocytes in developing cerebellum. AB - Newborn rat cerebellum microexplants cultured in Minimal Essential Medium with glucose and insulin released plasminogen activator (PA), which was detected in living cultures by a substrate overlay assay. Gel electrophoresis of cerebellum conditioned medium followed by zymography resolved PA activity in two separate bands of 48,000 and 75,000 daltons apparent mol. wt. Using specific antisera, these bands were shown to be respectively urokinase and tissue-type PA. Cerebellum conditioned medium as well as purified human urokinase induced the proliferation and outgrowth of glial fibrillary acid protein-positive cells from newborn cerebellar microexplants. The effect was suppressed by the serine protease inhibitor phenyl methanesulfonylfluoride. Since PAs are most likely of neuronal origin, we suggest that at least one of these proteases acts as a neuronoglial mitogenic signal during development. PMID- 4039965 TI - Behavioral effects of hippocampal system lesions on rats in an operant paradigm. AB - The effects on both operant and non-operant behavior during an operant task of various types of neural damage involving the hippocampal system were studied in adult male Sprague-Dawley rats. Various lesion types localized in the septal hippocampal area all produced higher than control levels of operant responding under both a contingent variable interval and a non-contingent variable time schedule, an effect opposite to that seen in rats with ventral mesencephalic tegmental lesions. A different lesion effect was seen for the non-operant activity measure in that an activity hierarchy was noted, with colchicine-induced granule cell lesions producing the greatest activity increase and kainic acid induced pyramidal cell lesions producing virtually no increase. Operant response rate was very sensitive to a switch in response contingency in that all groups significantly reduced operant responding while on the non-contingent schedule. This effect was not seen for the non-operant activity measure which appeared to be far less sensitive to contingency changes. The significance of these results to an understanding of the behavioral functioning of this system is discussed with some emphasis placed on their applicability to clinical cases of hyperactivity. PMID- 4039966 TI - Direct evidence for enhanced axon sprouting in adult rats exposed to ethanol in utero. AB - The anterograde transport of horseradish peroxidase (HRP) was utilized to examine the post-lesion expansion of the commissural projection to the molecular layer of the dentate gyrus in adult rats prenatally exposed to ethanol, and in normal and pair-fed controls. Mean daily ethanol consumption by the pregnant dams was 12.0 +/- 1.6 g/kg. Similar consumption in a separate group of pregnant dams produced mean blood ethanol concentrations of 102.8 +/- 5.2 mg/dl of blood. The commissural terminal field of rats exposed to ethanol in utero and given unilateral entorhinal lesions as adults exhibited a significantly greater expansion compared to controls. There were no differences in the HRP-labeled terminal fields between normal and pair-fed animals with similar lesions, suggesting that the effect in the ethanol-exposed rats was due to ethanol teratogenicity rather than reduced caloric intake. Furthermore, the effect was not a function of altered organization of commissural and perforant path terminal fields (terminal field overlap). These data demonstrate that exposure to ethanol in utero produces long-lasting alterations in lesion-induced axon sprouting. PMID- 4039967 TI - Ocular pharmacokinetics of subconjunctivally versus intravenously administered 6 mercaptopurine. AB - The levels of 6-mercaptopurine (6-MP) were measured in the anterior chamber aqueous, the vitreous and the serum of rabbits 0.5, 1, 2, 4, 8 and 12 hours following subconjunctival or intravenous injection of 10 mg/kg in 0.5 mL of saline, the maximum tolerated dose as determined experimentally. The mean peak concentrations of 6-MP in the aqueous and the vitreous respectively of the subconjunctivally injected eyes were 15 and 10 times those achieved in all the eyes following intravenous administration. The bioavailability of the drug over 12 hours was 21.67 micrograms/h in the aqueous and 22.22 micrograms/h in the vitreous following subconjunctival administration but only 1.47 and 3.50 micrograms/h respectively following intravenous administration. The serum concentration of 6-MP following subconjunctival injection was about half that following intravenous administration. PMID- 4039968 TI - An ultrastructural investigation of Leishmania donovani infection in genetically resistant and susceptible mouse strains. AB - Natural resistance to the growth of Leishmania donovani in mice is controlled by a gene (Lsh) which is expressed, in an unknown fashion, in macrophages. Early net growth rate of the parasite is much higher in mice strains bearing the susceptible allele (Lshs) than in resistant (Lshr) mice. Intracellular events occurring in the Kupffer cells during this period have been studied at the ultrastructural level. It was found that the number of dividing amastigotes per thin section of infected cell was approximately 10-fold greater in susceptible (B10.A SgSn) than in resistant (A/J) strains of mice, both 7 and 14 days following infection. These findings support the hypothesis that high natural resistance to leishmaniasis (Lshr) is expressed as a microbistatic effect, exerted within the parasitized macrophage of the host. PMID- 4039969 TI - Serum cortisol levels in child cardiac patients. PMID- 4039970 TI - Prevalence of Chlamydia trachomatis and genital mycoplasmas in asymptomatic women. AB - To establish the prevalence of Chlamydia trachomatis, Mycoplasma hominis and Ureaplasma urealyticum in women attending a family planning and a prenatal clinic in Halifax, cervical swabs were obtained at the time of the first visit from 491 women who had no symptoms of genital infection. Among the women attending the family planning clinic M. hominis occurred in combination with C. trachomatis more frequently than expected (p less than 0.05). It occurred in the absence of U. urealyticum in only a few cases (13% of the occurrences in the family planning clinic and 6% of those in the prenatal clinic). C. trachomatis was significantly more prevalent in women under 25 years of age (p less than 0.04). However, mycoplasmas were as prevalent in women over 30 years as in those under 30. There were no significant differences in the infection rates of the organisms by trimester among pregnant women. More research is necessary for a proper understanding of the role of M. hominis and U. urealyticum in genitourinary infections and pregnancy outcomes. PMID- 4039971 TI - Reliability of an in vitro short-term assay to predict the drug sensitivity of human breast cancer. AB - The feasibility and reliability of an in vitro assay that evaluates drug interference on nucleic acid precursor incorporation were investigated on 135 previously untreated locally advanced breast cancers. The assay, which was carried out on tumor fragments incubated for 3 hours with drugs, proved to be feasible on a sufficiently high percentage of biopsy specimens (70%) for routine clinical use. In vitro drug activity evaluated with this assay appeared to reproduce the clinical patterns of sensitivity of the tumor type as well as of the individual tumors. In fact, in vitro response rates to conventional agents resembled the clinical response rates reported for the same agents used in monochemotherapy. From a retrospective--correlative study carried out on 41 patients treated in vitro and in vivo with the same drugs (Adriamycin [doxorubicin] and vincristine), in vitro effect of Adriamycin on 3H-uridine incorporation appeared significantly correlated with clinical response (overall agreement, 78%; P = 0.0032) with specific agreements of sensitivity and resistance of 75% and 81%, respectively. PMID- 4039972 TI - Anticarcinogenic action of an alcohol-insoluble fraction (LAP1) from culture medium of Lentinus edodes mycelia. AB - From the culture medium of Lentinus edodes mycelia, water-soluble material (LEM) was prepared and further fractionated by alcohol precipitation and gel filtration on Sepharose 6B. The resulting fraction of xylose-rich proteoglycan at the void volume was designated as LAP1. The 25% and 50% survival rates of hepatoma-bearing rats were raised by intraperitoneal (i.p.) administration of LAP1 at doses of 3 10 mg/kg (an optimum dose, 3 mg/kg). This fraction did not suppress in vitro cell proliferation of the hepatoma. Moreover, the i.p. administration of LAP1 significantly augmented the activity of macrophage-migration inhibition of the splenic cells from hepatoma-bearing rats in the early stage after transplantation. Thus, the anticarcinogenic action of LAP1 would partly be interpreted by host-dependent immunomodulation. PMID- 4039973 TI - Antitumor activity of l-OHP in mice. AB - The isomeric mixtures of platinum complexes of diaminocyclohexane (DACH) had been found active on several murine tumors. A recent separation of the oxalato platinum complex of trans-l-DACH isomer allowed more precise screening studies and permitted the selection of one compound: l-OHP was submitted to our murine tumor screening system. The drug was given: (a) at doses of 1-12 mg/kg i.p. or i.v. on day 1, 5 and 9 compared to identical doses of cis-dichlorodiamine platinum II (CDDP) in L1210 bearing mice and (b) to AkR leukemia, LGC lymphoma, glioma 26, B16 melanoma, MA 16-C mammary carcinoma and Lewis lung carcinoma bearing mice at 2 dosages: 5 mg/kg (minimal effective dose on L1210), and 8 mg/kg (subtoxic dose in L1210). Acute LD10 and LD50 appeared similar to CDDP and l-OHP. l-OHP administered i.p. was more active on L1210 than CDDP. On L1210 grafted intracerebrally and on LGC lymphoma l-OHP increased significantly the lifespan while CDDP was inactive. On AkR leukemia, both drugs were active but l-OHP was less toxic. Both drugs were inactive on murine solid tumors. No renal toxicity was observed with l-OHP as compared to CDDP. PMID- 4039974 TI - Inhibition of benzo(a)pyrene and benzo(a)pyrene-trans-7,8-diol metabolism and DNA binding in mouse lung explants by ellagic acid. AB - The effect of ellagic acid, a naturally occurring plant phenol, on the binding to DNA and metabolism of benzo(a)pyrene (BP) and trans-7,8-dihydro-7,8 dihydroxybenzo(a)pyrene (BP 7,8-DHD) in cultured explants of strain A mouse lung was investigated. The explants were cultured in a rocking organ culture chamber for 16 h in the presence or absence of 10, 25, 50, and 100 microM ellagic acid. These concentrations of ellagic acid were nontoxic as determined by biochemical and histological methods. The ellagic acid was then removed from the cultures, and the explants were incubated with either 1 microM [3H]BP or [3H]BP 7,8-DHD for 24 h. Explant DNA was isolated using hydroxylapatite chromatography, and the BP metabolites in the medium were analyzed by high-pressure liquid chromatography. Ellagic acid (50 microM) inhibited the binding of BP and BP 7,8-DHD to lung DNA by 46 to 50% and 60 to 70%, respectively. High-pressure liquid chromatography analysis showed that ellagic acid (100 microM) inhibited the metabolism of BP by 20 to 40% and of BP 7,8-DHD by 20%, as indicated by the increased amounts of unmetabolized substrates and decreased amounts of metabolites in the medium. The major BP:DNA adduct in the explants was 7R-N2-[10 beta-[7 beta, 8 beta, 9 alpha trihydroxy-7,8,9,10-tetrahydrobenzo(a)pyrene]yl: deoxyguanosine, and its formation was reduced by 60 to 65% in the presence of 100 microM ellagic acid. These data suggest that the reduction of BP and BP 7,8-DHD metabolite binding to DNA by ellagic acid may have been due to inhibition of the formation and/or removal of BP 7,8-diol-9,10-epoxide prior to its binding to DNA. PMID- 4039976 TI - Effects of combined treatments of cis-diamminedichloroplatinum(II), 5 fluorouracil, and X-rays on growth of human cancer nodules maintained in continuous organotypic culture. AB - The effectiveness of combined treatments of cis-diamminedichloroplatinum(II) (cis DDP), 5-fluorouracil (5-FUra), and X-rays on growth inhibition of human pulmonary cancer nodules maintained in continuous organotypic culture was tested. To obtain the most effective growth inhibition, a cis-DDP treatment had to be preceded by an X-irradiation, whereas a 5-FUra treatment had to be postirradiated. This indicates the importance of the order in which the different combinations must be done. A mixture of 5-FUra and cis-DDP was even more effective than the X-ray and drug combination but only for a short period of time; reduction of nodule size and cell loss occurred during the 2 weeks following the treatment. After this period, as happened also with nodules treated with 5-FUra alone, vigorous regrowth occurred after treatment with cis-DDP plus 5-FUra, and all the nodules regained the size of the controls sooner or later. It is to be noted that, if X rays were applied after a 5-FUra treatment, this regrowth is inhibited at least up to 45 days after the treatment. PMID- 4039975 TI - Estrous cycle modification of rat mammary tumor induction by a single dose of N methyl-N-nitrosourea. AB - The potential of individual stages of the rat estrous cycle to alter the incidence and subsequent behavior of mammary carcinomas induced by a single dose of N-methyl-N-nitrosourea on diestrus, proestrus, or estrus was examined. Mean latencies to first tumor appearance in diestrous, proestrous, and estrous groups were 86, 71, and 69 days, respectively (P less than 0.05 diestrus versus proestrus, estrus). Tumor incidence in diestrous rats given injections (73%) was significantly lower than in proestrous (87%) or estrous (89%) animals given injections, as was the mean number of tumors per rat. However, the number of days required for tumors to reach 1 cm in diameter in diestrous animals given injections (13.0) was significantly lower as compared with tumors in rats given injections during proestrus (19.3) or estrus (22.2). In later growth stages, the diestrous tumor doubling time was one-half that of tumors in proestrous rats given injections. Flow cytometric analysis of tumor tissues during midlog and later growth phases did not reveal any significant changes in ploidy or growth fractions between groups. Further, there was no significant difference in tumor cytosol estrogen receptor incidence, affinity (Kd), or content between groups, although tumor cell nuclear receptor for estrogen was higher (38.3 fmol/mg DNA; P less than 0.05) in proestrous rats given injections than in diestrous (21.6) or estrous (21.8) animals given injections. These data support the concept that the prevailing hormonal profile of the estrous cycle at the time of tumor initiation modulates the subsequent induction of mammary tumors. Further, the absence of any observed difference in tumor behavior between proestrous and estrous rats given injections suggests that prolactin does not impose an additive or synergistic effect on the initial stage of tumor induction when mammary gland epithelial cell DNA is previously stimulated by estrogen. PMID- 4039977 TI - Altered actin cytoskeletal patterns in two premalignant stages in human colon carcinoma development. AB - Primary culture of human colonic biopsies converts the single cell thick epithelial layer from a highly indented sheet in vivo into a flat patch on the surface of a Petri dish. Migration of cells from biopsies in a continuous sheet to form the patch cultures allows the cultured cells in large part to retain the junctional complexes and membrane interdigitations which connect adjacent cells in vivo and therefore to maintain their spatial relationships to neighboring cells. Migration of the cells onto a flat surface also allows visualization of their actin cables (E. Friedman, M. Verderame, S. Winawer, and R. Pollack, Cancer Res., 44: 3040-3050, 1984). Actin organization patterns have been studied in primary patch cultures of colonic epithelial cells from four stages in the development of colon cancer: normal tissue, normal-appearing but preneoplastic cells characteristic of familial polyposis patients, benign tumors or adenomas from familial polyposis patients, and benign and malignant tumors from patients in the general population. Carcinomas exhibited the least number of actin cables, while adenomas contained the greatest concentration. Similar actin patterns were seen in both familial polyposis and nonpolyposis adenomas. The preneoplastic prebenign tumor stage characteristic of familial polyposis patients had less actin cables than either normal cells or benign tumor cells. Thus actin organization loss characterized the transition from the normal colonic epithelial cell to the preneoplastic nontumor cell. The ability to form actin cables was then regained with the transition from the preneoplastic pretumor cell to the benign tumor cell and lost again with the benign tumor to malignant tumor transition. The complexity of these changes in actin organization during the step wise transformation of colonic epithelial cells was not predicted from the simple model of actin cable loss accompanying fibroblast transformation. PMID- 4039978 TI - Cisplatin, doxorubicin, and cyclophosphamide chemotherapy for advanced endometrial carcinoma. AB - Nine of 19 patients (47%) with widespread or recurrent endometrial carcinoma responded to chemotherapy with cisplatin, doxorubicin, and cyclophosphamide. Two complete clinical responses and seven partial responses were achieved. A "second look" laparotomy documented the complete response in one patient. The addition of cisplatin to doxorubicin and cyclophosphamide increased toxicity without increasing the antitumor activity previously reported for the two-drug combination. Performance status had a marked influence on response, while sites of metastases, amount of residual disease, and histologic grade did not affect the response rate. A schema for the treatment of patients with endometrial carcinoma with progestins and/or cytotoxic chemotherapy is suggested. PMID- 4039979 TI - Combined chemotherapy (vindesine, lomustine, cisplatin, and cyclophosphamide) and radical radiotherapy in inoperable nonmetastatic squamous cell carcinoma of the lung. AB - Thirty-three evaluable patients with locally advanced squamous cell carcinoma of the lung were entered in a phase II study combining chemotherapy (vindesine, lomustine, cisplatin, and cyclophosphamide) and radical radiotherapy. Fourteen patients had an objective response rate of 42% (two complete responses and 12 partial responses) with the first two cycles of chemotherapy. All patients received radiation therapy to the primary tumor, mediastinum, and supraclavicular nodes, and responders to chemotherapy received four additional cycles. On final evaluation, 18 patients (54.5%) achieved complete response and six patients (18%) achieved partial response. The objective response rate was 73% with the combined therapy. The median survival was 15.9 months. Toxicity was acceptable. We conclude that our results justify a phase III study comparing combined treatment versus radiotherapy alone. PMID- 4039980 TI - Treatment of advanced endometrial carcinoma with doxorubicin and cisplatin: effects on both untreated and previously treated patients. AB - Sixteen patients with advanced (International Federation of Gynecology and Obstetrics stage III and IV) adenocarcinoma of the endometrium were treated with twelve 28-day cycles of doxorubicin and cisplatin. Response was achieved in 92% of patients (11 responses among 12 patients) who had received no prior chemotherapy and in 50% (two responses among four patients) of previously treated patients. Median survival was 10 months. Doxorubicin and cisplatin were readily administered on an outpatient basis with comparatively low major toxic effects, primarily hematologic, renal, and gastrointestinal. These results indicate that doxorubicin and cisplatin combination therapy is effective with acceptable toxicity in patients with advanced endometrial carcinoma. PMID- 4039981 TI - Effect of cyclophosphamide on the mitomycin-induced syndrome of thrombotic thrombocytopenic purpura. PMID- 4039982 TI - Microscopic studies of the vascular hyperplasia in lymphoid proliferations susceptible to lymphomatous transformation. PMID- 4039983 TI - Histoenzymological circuits involving nuclei of medulla oblongata of golden hamster (Mesocricetus auratus)--a topographical and functional evaluation of acetylcholinesterase activity. PMID- 4039984 TI - Pharmacokinetics and toxicity of the epipodophyllotoxin derivative etoposide (VP 16-213) in patients with gestational choriocarcinoma and malignant teratoma. AB - Serum levels of etoposide obtained 5 min after administration of 100 mg/m2 were between 11 and 30 micrograms/ml. By 24 h after drug administration, serum levels had fallen to between 0.19 and 1.11 micrograms/ml. Interpatient variation of etoposide serum concentrations obtained 5 min after drug administration was low, whereas interpatient variation 24 h later was noticeably higher. A significant correlation was observed (r = -0.698) between the WBC nadir and the mean etoposide serum concentrations, measured 24 h after drug administration, in patients receiving etoposide in combination with cyclophosphamide and actinomycin D. However, a relationship was not observed in those patients receiving etoposide alone. There was no observed difference in the efficacy or toxicity of 500 mg/m2 etoposide when the dose was administered either as 100 mg/m2 on each of 5 consecutive days or as 250 mg/m2 on days 1 and 3. There was no significant difference between AUC values calculated from etoposide concentration versus time profiles in patients receiving the drug on days 1 and 3 and those values obtained with the 5-day schedule. Patients resistant to a conventional dose of etoposide were given a higher dose of 1 g/m2/24 h, but this schedule did not cause an increase in efficacy despite an increase in serum levels of the drug. CSF levels in two of these patients receiving high-dose etoposide were 1.28% and 2.09% of the serum concentrations. PMID- 4039985 TI - Phase II trial of 5-fluorouracil, adriamycin and cisplatin (FAP) in advanced gastric cancer. AB - Twenty patients (15 male, 5 female) with nonresectable gastric adenocarcinoma were treated with FAP (5-fluorouracil 300 mg/m2 IV on days 1-5, adriamycin 50 mg/m2 IV on day 1, cisplatin 20 mg/m2 IV on days 1-5). Each course was repeated every 21 days. Eighteen patients were evaluable for response. The median age was 51 years, the range extending from 34 to 68. None had undergone chemotherapy. The median Karnofsky performance score was 80%. Nine (50%) partial responses (PR) and eight (44%) cases of stable disease (SD) were observed. One patient showed progression of the disease and died after 6 months. The median duration of response was 6+ months for PR and 6 months for SD. The median survival was 12 months. FAP toxicity was moderate, with the median WBC nadir 3.2 X 10(9)/l (range 0.7-4.2). One patient in PR died of septicemia. Nausea and vomiting were not dose limiting. Neuropathy was mild in four and moderate in two patients. This FAP combination appears to be as effective with respect to response rate and duration as reported for 5-fluorouracil, adriamycin and mitomycin C (FAM). PMID- 4039986 TI - A comparison of the thrombolytic and hemorrhagic effects of tissue-type plasminogen activator and streptokinase in rabbits. AB - Tissue-type plasminogen activator (t-PA) is a promising thrombolytic agent because it can produce thrombolysis without inducing a plasma proteolytic state. It is uncertain if this potentially important feature renders t-PA less hemorrhagic than other plasminogen activators. We have compared the hemorrhagic and thrombolytic effects of t-PA and streptokinase in rabbits. Streptokinase, 4000 U/kg/hr over 4 hr, failed to produce significant thrombolysis and 8000 U/kg/hr streptokinase over 4 hr produced only 28 +/- 6% thrombolysis. Both streptokinase regimens were associated with a plasmin-mediated plasma proteolytic state and both streptokinase regimens produced a significant increase in hemorrhage that was evident within 15 min of beginning the infusion and was progressive over the 4 hr of drug administration. In contrast, t-PA in a dose of 7500 U/kg/hr produced 35 +/- 6% thrombolysis, but it did not produce a plasmin mediated plasma proteolytic state or a significant increase in hemorrhage over the 4 hr of infusion. t-PA in a dose of 15,000 U/kg/hr produced 85 +/- 4% thrombolysis but was associated with a plasmin-mediated proteolytic state and produced significant bleeding which, in contrast to streptokinase-induced bleeding, was delayed in onset. Therefore, t-PA induced less hemorrhage than streptokinase at doses that produced more effective thrombolysis. Bleeding with both thrombolytic agents was associated with a plasmin-mediated proteolytic state. PMID- 4039987 TI - Human tissue-type plasminogen activator: from the laboratory to the bedside. PMID- 4039988 TI - Ultrastructural and immunomorphologic study of perinuclear filaments in Merkel cell tumors. PMID- 4039989 TI - A routine solid-phase assay for the binding capacity of sex hormone binding globulin. PMID- 4039990 TI - Mechanisms concerned with blood pressure variability throughout the day. AB - Blood pressure variability throughout the day has been found to be inversely related to baroreflex sensitivity, as is the response to injected phenylephrine, mental stress and sleep. It is concluded that variability in blood pressure results in some degree from defective buffering of blood pressure by the baroreceptors. PMID- 4039991 TI - Blood pressure variability in health, hypertension and autonomic failure. AB - 24h intra-arterial pressure monitoring was used to examine blood pressure variability in 5 normal volunteers, 137 subjects with suspected or established essential hypertension and 9 subjects with autonomic failure. Subjects with autonomic failure showed increased short-term blood pressure variability while active but reduced values at rest. Heart rate variability was low at all times. 24h recordings were reduced to hourly mean values and two indices of variability derived - day-night difference and average hourly change. For blood pressure, subjects with autonomic failure showed negative values of the former but high values of the latter; both indices of heart rate variability were low. In the remaining group, the relationship of these indices to constitutional factors, mean blood pressure and indices of physical activity during the study was explored. Day-night difference in systolic pressure was negatively correlated with mean pressure and average hourly change positively related to age. No other relationship was significant. PMID- 4039992 TI - Superiority of 24-hour measurement of blood pressure over clinic values in determining prognosis in hypertension. PMID- 4039993 TI - Technique for 24 hour recording of continuous high fidelity arterial pressure and electrocardiogram in ambulatory patients. PMID- 4039994 TI - Reproducibility of blood pressure values in normotensive subjects. AB - The reproducibility of whole-day blood pressure (BP) averages was evaluated in 56 normal volunteers. Blood pressure was monitored using a non-invasive automatic device that measured BP at 7.5 minute intervals for a 24h period. The whole-day systolic BP averages were closely similar on the two study days, 119 +/- 10 (S.D) and 117 +/- 11 mm Hg. A difference between the two whole-day averages of systolic blood pressure of greater than 10 mm Hg was found in 10 subjects. Values for the diastolic BP averages were 75 +/- 7 and 73 +/- 8 mm Hg with differences of greater than 5 mm Hg found in 15 subjects. Strong consistency of BP averages during the separate study days was also found for shorter monitoring periods: the 2h period (8 AM to 10 AM), the daytime period (6AM to 10PM) and the nighttime period (10PM to 6AM). Thus, blood pressure values obtained using a non-invasive ambulatory monitoring device are reproducible in the majority of normotensive control subjects. PMID- 4039995 TI - Secretory otitis media: grommets and swimming. PMID- 4039996 TI - Effects of testosterone on the development of autoimmune thyroiditis in two strains of chicken. AB - The effect of testosterone on organ-specific spontaneous autoimmune thyroiditis (SAT) was examined in two strains of chicken: the Obese (OS) strain, which develops SAT at several weeks of age and the control Special C (Sp. C) strain. Both were originally selected from the C strain and are homozygous for the B13 major histocompatibility haplotype. Testes development and testosterone levels in the OS strain were considerably less than those found in comparably aged birds of the Sp. C strain. Testosterone supplementation of the OS strain significantly decreased thyroid infiltration by lymphocytes while castration of the Sp. C strain significantly enhanced infiltration. These results suggest that testosterone reduces SAT and that the hormonal constitution in both strains of chicken affect the frequency of occurrence and severity of this disorder. PMID- 4039997 TI - Diffuse hypoplasia of the aorta as a possible cause of cardiac hypertrophy. AB - Left ventricular hypertrophy is caused by a wide variety of cardiovascular conditions, including systemic hypertension, aortic valvular disease, and hypertrophic cardiomyopathy. This paper describes a case of diffuse hypoplasia of the aorta in left ventricular hypertrophy. This condition has not previously been well documented. We emphasize the need for evaluation of aortic dimension when systolic hypertension and vascular bruits are observed in association with myocardial hypertrophy. PMID- 4039998 TI - Temporal variation in the disposition of theophylline and its metabolites. AB - The temporal aspects of theophylline disposition are of interest, as there are predictable time-dependent fluctuations in the pulmonary function of patients with asthma and theophylline serum concentrations may vary throughout a 24-hour period. We studied the extent to which there are significant temporal changes in theophylline kinetics and the relative contribution of distribution, metabolism, and excretion to this phenomenon. Eight healthy men received an intravenous dose (6 mg/kg) of theophylline at 8 AM and 8 PM at 1-week intervals. Serum and urine were analyzed for theophylline and its three major metabolites by HPLC. Distribution volumes and total body and nonrenal clearances showed no differences between morning and evening dosing. The elimination rate was 12% greater after morning dosing. Renal clearance was 24% greater after morning dosing and was accompanied by an increased excretion fraction of unchanged theophylline. Based on total urinary metabolite excretion and the metabolite serum AUCs, there was no evidence of time-dependent variation in theophylline biotransformation. Although theophylline renal clearance is greater after morning dosing, it is only a small fraction of the overall drug elimination and does not change the total body clearance after morning or evening dosing. PMID- 4039999 TI - Appearance of ranitidine in breast milk following multiple dosing. PMID- 4040000 TI - Premenstrual syndrome. AB - PMS is a constellation of symptoms, both somatic (breast tenderness, bloating, headache) and psychologic-behavioral (irritability, hostility, depression) that recur prior to the menses in about 5% to 20% of all menstruating women. Such women should be evaluated with a thorough history and physical examination, and if the diagnosis is firmly established by observing a temporal relationship of the symptoms with the premenstruum, therapy should be initiated. When treating PMS, reassurance should always be offered to the patient along with counseling regarding life-style and dietary changes. Symptomatic relief may be provided with any number of medications, including diuretics, NSAIDs, and possibly progesterone. Oral contraceptive therapy may also be helpful. Although patience is certainly required in order to deal with this often frustrating problem, it should be remembered that patient satisfaction is commonly within reach. PMID- 4040001 TI - Age-sex differences in the expression of agonistic behavior in rhesus monkey (Macaca mulatta) groups. AB - Both age and sex influence rhesus monkey agonistic behavior. In intragroup episodes, submission was most frequent in juveniles, but aggression increased steadily with age, albeit much more sharply in females. As infants, males were more often involved in agonistic behavior than were females, but this sex difference reversed with age. A notable change in the frequency and forms of agonistic expression occurred in adolescent males. By the time they became adults, their participation in agonistic episodes was silent and brief and rarely involved biting. Adolescent males received high frequencies of aggressive responses, and this is hypothesized to account for the marked shift in adult male patterns of participation in intragroup agonistic interactions, as relative to females whose basic pattern of agonistic expression does not change with age. PMID- 4040002 TI - Early experience and social processes in rhesus macaques (Macaca mulatta): II. Complex social interaction. AB - Differences in simple and complex social behavior were examined between monkeys reared with either animate, though nonconspecific, or inanimate surrogate mothers. In the first experiment, members of each rearing condition were formed into 6-member social groups for ten 5.5-hr trials. In the second experiment, members of each rearing condition were formed into social groups twice daily, one formation comprising all 6 group-members and one comprising 5 group-members, with a different individual excluded each day. Although members of both groups displayed deficient forms of social behavior, individuals reared with animate companions were able to use their limited social repertoires in more sophisticated ways, depending upon the social context. The results are discussed in terms of two "tasks" of social ontogeny, the acquisition of behavioral and social competences. PMID- 4040003 TI - Different sister chromatid exchange rates in XX and XY cells of a pair of human chimeric twins. AB - To explore the influence of sex on sister chromatid exchange (SCE) level, a pair of chimeric twins was examined for differences in SCE frequency between the XX and XY cells present in each individual. By this method, the influence of possible differences in environmental exposure was eliminated. SCE levels were varied by growing the cells in media containing 0, 1.3 X 10(-7), or 6.5 X 10(-7) M melphalan. XX cells showed a higher SCE count than XY cells. This difference increased with increasing SCE level and ranged from 5.4% to 7.8% (P = 0.0003) of the SCE counts. Only about 2% of the difference could be explained by the higher amount of DNA present in the XX cells than in the XY cells. In this case XX cells seemed to be more sensitive to SCE-inducing agents than XY cells. PMID- 4040004 TI - Structure and activity of salivary gland chromosomes of Drosophila gibberosa. AB - In Drosophila gibberosa the maximum secretory output of the salivary glands is in the prepupa rather than in the late third-instar larva. Using salivary chromosome maps provided here we have followed puff patterns from late second-instar larvae through the time of histolysis of the salivary glands 28-32 h after pupariation and find low puff activity correlated with low secretory activity throughout much of the third larval instar. Ecdysteroid-sensitive puffs were not observed at the second larval molt but do appear prior to pupariation initiating an intense cycle of gene activity. The second cycle of ecdysteroid-induced gene activity a day later, at the time of pupation, appears somewhat damped, especially for late puffs. Salivary chromosome maps provided here may also be used to identify homologous loci in fat body, Malpighian, and midgut chromosomes. PMID- 4040005 TI - Luteinizing hormone beta-subunit mRNA amounts increase during the preovulatory surge of luteinizing hormone in the ewe: the highest levels are observed at the completion of the peak. AB - Amounts of mRNA for luteinizing hormone (LH) beta-subunit were assessed during selected times in the normal estrous cycle of sheep. These times spanned the luteal phase through the preovulatory LH surge, and included groups designated as: (i) day 12 of the cycle (day 12); (ii) 24 hr before the onset of the expected behavioral estrus (E - 24); and (iii) 5, 15, and 25 hr after the onset of behavioral estrus (E + 5, E + 15 and E + 25). These groups were characterized by criteria such as serum and pituitary LH concentrations, serum progesterone, and ovarian morphology. Specific LH beta-subunit mRNA was evaluated by Northern transfers, using a specific bovine LH beta cDNA probe. Slopes were determined using a linear regression analysis and then expressed as fold stimulation relative to the values for the day 12 group. The results indicate that LH beta mRNA amounts increase after day 12, reaching a value of approximately 12-fold by E + 25. When correlated with serum and pituitary LH amounts, it is observed that the amounts of beta mRNA increase in a fashion parallel to serum and pituitary LH concentrations through the time E + 5. After this time, LH beta mRNA amounts continue to increase despite a dramatic fall in both serum and pituitary LH. These results suggest that LH beta mRNA amounts are regulated during the LH preovulatory surge. PMID- 4040006 TI - The effect of topically applied prostaglandin inhibitors on the laser-induced disruption of the blood aqueous barrier. AB - The therapeutic effect of topically applied prostaglandin inhibitors on the laser induced disruption of the blood-aqueous barrier was investigated in six series of five rabbits each. One series was not coagulated and served as baseline, and in a reference group laser coagulation was performed without pretreatment with a prostaglandin inhibitor. In four series the iris laser coagulation of the left eyes was preceded by topical application of a prostaglandin inhibitor. The right eyes served as controls for the contralateral effect on the blood aqueous barrier. After laser coagulation the intraocular pressure was monitored at 10-min intervals, and the anterior chamber was tapped for analysis of the protein concentration and the lactate dehydrogenase activity. Pretreatment with dexamethasone eyedrops and indomethacin eyedrops markedly blocked the laser induced disruption of the blood-aqueous barrier. The level of protein concentration in the aqueous humor after laser coagulation was much less after pretreatment with dexamethasone or indomethacin eyedrops. The effect was significant, both for the laser-treated eyes and for the noncoagulated fellow eyes (p less than 0.025). The subconjunctival pretreatment with dexamethasone 1 or 24 h before laser coagulation had no significant effect with respect to the protection of the blood aqueous barrier. PMID- 4040007 TI - [Therapeutic effects of prostaglandin E1 on 59 cases of heart dysfunction]. PMID- 4040008 TI - [Acute Cryptosporidium enteritis without immunologic weakness]. PMID- 4040009 TI - Embryonic head posture and palatal shelf elevation. AB - During embryonic and fetal stages of human development, elongation and straightening of the neck occurs. Authors have suggested that the resulting change in head posture lifts the lower border of the mandible from the pericardial region, so allowing jaw movements to assist the withdrawal of the tongue from between the palatal shelves. This aids elevation of the palatal processes prior to fusion. This paper reports on histological sections of 28 mm twin embryos which demonstrate that palatal elevation can take place in the absence of elongation and straightening of the neck, demonstrated by observation of existence of cephalic, pontine and cervical neural flexure of the brain. PMID- 4040010 TI - Creamatocrit, carbon content, and energy value of pooled banked human milk: implications for feeding preterm infants. AB - It is convenient to calculate milk energy from the creamatocrit but in order to assess the accuracy with which energy content can be predicted in this way, the creamatocrit, the percentage of carbon, and the calorie value of milk were determined in 11 samples of pooled pasteurised human milk. The calculated milk energy was compared with direct measurements of milk energy by static bomb calorimetry. The errors in calculation ranged from -5.6 kcal/100 ml to + 19.5 kcal/100 ml in milk samples whose measured energy was 34.5 to 63.1 kcal/100 ml. In 9 milk samples energy values were over-estimated by calculation and in the remaining 2 milk samples energy values were underestimated. The correlation between creamatocrit and measured energy value in pooled pasteurised milk was weaker than in previous studies using fresh milk. The percentage carbon was determined in our milk samples as a measure of their total organic constituents, and this appeared to be a more accurate predictor of milk energy than the predictive value of the creamatocrit which is only a measure of milk fat. In pooled pasteurised milk the relatively weak predictive value of the creamatocrit may be due to variations in the other constituents of milk apart from fat which provide energy, namely protein and lactose. PMID- 4040011 TI - Animal models of male infertility: mice bearing single-gene mutations that induce infertility. AB - Genetically defined mouse models of male infertility are described in the present report. The mice were rendered infertile by one of the following gene mutations: Ames dwarf, dwarf, flipper-arm, hightail, hypothyroid, little, pygmy, stubby. The effects of each gene mutation on testicular steroidogenesis and spermatogenesis were elucidated by a comparison of the mutant mice to their normal siblings. Testicular steroidogenesis was assessed directly by determining steroid secretion by testes perfused in vitro. The study provides the first comprehensive assessment of testicular function in the mutant mice. The eight gene mutations can be classified into two groups based on the results. One group of gene mutations (Ames dwarf, dwarf, flipper-arm, pygmy) specifically depress spermatogenesis and testicular steroidogenesis. The infertility of these mutant mice can be linked to the lowered total sperm production. The second group of gene mutations (hightail, hypothyroid, little, stubby) do not specifically depress either spermatogenesis or testosterone secretion. Subsequently, the etiology of the male infertility of the second group of mutant mice is unknown. We propose that these mutant mice provide valuable experimental tools for the study of male infertility and male reproduction. PMID- 4040012 TI - Inhibitory effect of [Asu1,7]-eel calcitonin on growth hormone-secretion in conscious, freely moving, male rats. AB - The effect of [Asu1,7]-eel calcitonin (ECT), which is an equipotent analog of eel calcitonin (CT), on GH secretion was investigated in freely moving conscious male rats. Pulsatile GH secretion was completely inhibited by iv injection of ECT (2.5 micrograms/rat). The mean 6-h plasma GH levels, 9.54 +/- 2.34 ng/ml (mean +/- SEM) in ECT-treated rats, were significantly lower than those in saline-treated rats (69.9 +/- 9.4 ng/ml, P less than 0.001). In order to examine the action of ECT on the central nervous system, 25 ng ECT dissolved in 10 microliters saline were injected into the lateral ventricle of conscious male rats. The bursts of GH secretion were completely abolished by this dose of intraventricularly (ivt) injected ECT. The mean 6-h GH levels 5.8 +/- 0.8 ng/ml, were also significantly lower than those in control rats (35.8 +/- 6.6 ng/ml, P less than 0.01). Serum Ca levels did not change after the ivt injection of 25 ng ECT but fell significantly after the iv injection of 2.5 micrograms ECT. In order to clarify the inhibitory mechanism of GH secretion by ECT, the effect of ECT on the release of GH elicited by prostaglandin E1 (PGE1), a well-known GH secretagogue acting directly on the pituitary, was examined in vivo as well as in vitro. Both ivt (2.5, 25, or 250 ng/10 microliters X rat) and iv (2.5 or 25 micrograms/rat) injections of ECT caused a significant and dose-dependent suppression of PGE1-induced GH rises in conscious rats. In contrast, 10(-8) to 10(-7) M ECT failed to affect the baseline secretion of GH and its release by 5 X 10(-6) M PGE1 from rat anterior pituitary tissues perifused in vitro. These findings suggest that ECT suppresses GH secretion in the rat, at least in part, through the central nervous system. PMID- 4040013 TI - Central nervous system regions involved in the estrogen-induced afternoon prolactin surge. II. Implantation studies. AB - In the intact cycling female rat, there is a surge of plasma PRL during the afternoon of proestrus. Ovariectomy on diestrous day 1 eliminated the PRL surge completely, and injection of 100 micrograms polyestradiol phosphate, a long acting estrogen, not only maintained the surge, but amplified and prolonged it. Bilateral implantation of an estradiol (E2)-containing cannula [diluted 1:4 with cholesterol (C)] in the medial preoptic area (MPO), but not in the cerebral cortex (CC), also maintained the surge. In long term ovariectomized rats, bilateral implantation of E2-containing cannulae (1:5, 1:10, 1:20, and 1:200) in the corticomedial amygdala (CMA) or ventromedial nucleus of the hypothalamus or a singular implantation in the third ventricle failed to induce a PRL surge 12 days later. Similar singular implantation in the anterior pituitary (AP) increased the basal levels of plasma PRL compared to those in C-implanted controls, but no surge was evident. Only bilateral implantation of E2 in the MPO induced a small but significant rise of plasma PRL at 1700 and 1900 h. Using higher concentration implants with a higher E2 concentration (1:4) in the MPO and sampling at shorter intervals, significant afternoon PRL surges were induced on days 2-4. However, systemic effects of E2, i.e. vaginal cornification and uterine weight enlargement, were also evident. Similar implants in other brain regions had the same results. Further increasing the E2 to C dilution from 1:10 to 1:200 eliminated the systemic effect of E2 implants, while the PRL surge-inducing ability persisted. It appears that the highest diluted E2 implants (1:150 and 1:200) gave the highest PRL response and persisted for the greatest number of days. Using the highly diluted E2 implants (1:100 and 1:200) in various brain regions, the MPO and the ventromedial hypothalamus were the most sensitive areas in inducing the PRL surge; the other areas studied, including suprachiasmatic nuclei, CMA, AP, and CC were ineffective. In conclusion, highly diluted E2 implants in the brain appear to be effective in obtaining a specific effect on the afternoon PRL surge; the CMA, suprachiasmatic nuclei, AP, and CC are not estrogen feedback sites for the induction of PRL release, and the MPO was the most sensitive area of the estrogen action in the brain regions examined for the induction of the afternoon PRL surge. PMID- 4040014 TI - Exposure to platelet-derived growth factor modulates the porcine aortic smooth muscle cell response to somatomedin-C. AB - Platelet-derived growth factor (PDGF) is a potent mitogen for smooth muscle cells, but to detect maximal stimulation by PDGF, the cells must be incubated with plasma. Somatomedin-C (Sm-C), a peptide growth factor that is present in plasma, has been shown to interact with PDGF synergistically to stimulate DNA synthesis in cultured fibroblasts. These studies were designed to test the hypothesis that PDGF interacted with Sm-C to stimulate smooth muscle cell replication and to compare the response of this cell type to that of fibroblasts. When PDGF or Sm-C was added individually to smooth muscle cell cultures, each growth factor induced only minimal increases in [3H]thymidine incorporation into DNA (i.e. PDGF, 3,400 +/- 1,120 to 54,900 +/- 1,550 cpm; Sm-C, 3,400 +/- 1,120 to 10,950 +/- 980 cpm). In contrast, addition of increasing concentrations of Sm-C to cultures that were continuously exposed to PDGF in the presence of Sm-C deficient plasma resulted in a synergistic increase in [3H]thymidine incorporation (3,400 +/- 1,120 to 54,500 +/- 1,800 cpm; P less than 0.001). To determine if Sm-C was required for smooth muscle cell replication, cultures were sequentially exposed to PDGF, followed by Sm-C-deficient plasma. The rate at which the non-Sm-C-exposed cells synthesized DNA was retarded compared to that of cells exposed to Sm-C-containing plasma; however, 68% nuclear labeling was present after 44 h of incubation. To exclude the possibility that some cellular secretory product was substituting for Sm-C, the medium was changed every 2 h and replaced by fresh Sm-C-deficient medium. Using these test conditions, exposure to PDGF and Sm-C-deficient plasma induced only 11% labelling. Readdition of pure Sm C to this medium restored nuclear labeling to 82% at 44 h. Other variables that appeared to modulate the cellular response to Sm-C were culture density and simultaneous PDGF exposure. Sm-C and PDGF both appear to be potent mitogens for porcine aortic smooth muscle cells, and when added together to quiescent cultures, their effects are synergistic. Smooth muscle cells appear to require Sm C to initiate DNA synthesis, and in its absence produce a Sm-like factor that can partially compensate for Sm-C deficiency and allow replication. PMID- 4040015 TI - Site-specific DNA binding by the bacteriophage SP01-encoded type II DNA-binding protein. AB - The bacteriophage SP01 genome encodes a virus-specific type II DNA-binding protein, TF1. The bacterial proteins of this ubiquitous and evolutionarily conserved class are thought to bind non-specifically to DNA. In contrast, the experiments described here demonstrate that TF1 binds to specific sites in SP01 DNA. Several of these sites have been characterized by DNase I 'footprinting' and four of them have been shown to overlap strong phage promoters for Bacillus subtilis RNA polymerase holoenzyme. We speculate on the possible structural basis of site-selective DNA binding by a protein of this class. PMID- 4040016 TI - Ova of Schistosoma mansoni in urine. PMID- 4040017 TI - Errors in gated equilibrium radionuclide measurements of resting left ventricular ejection and filling. AB - An assessment was made of the reproducibility (between study differences) interobserver variability and intraobserver variability of 7 radionuclide measurements describing both resting left ventricular ejection (ejection fraction -EF, average ejection rate--AVER, peak ejection rate--PER, time to peak ejection rate--TPER) and filling (average filling rate--AVFR, peak filling rate--PFR, time to peak filling rate--TPFR). Gated blood pool studies were performed one week apart in 42 patients and between study correlation coefficients for these measurements ranged from r = 0.58 (TPER) to r = 0.99 (PFR) but there were spontaneous changes in measurements of up to 82% (AVER). Interobserver variability was determined in 44 studies. Correlation coefficients for measurements obtained by two independent observers in 44 studies ranged from r = 0.87 (AVER) to r = 0.96 (TPFR) but spontaneous changes of up to 52% occurred (AVFR). Intraobserver variability was determined in 53 studies and correlation coefficients ranged from r = 0.95 (AVER) to r = 0.99 (AVFR, PFR). The maximum percentage difference between observations was 46% (AVER). Use of correlation coefficients alone to assess the reproducibility of these measurements fails to highlight the marked spontaneous changes which occur in left ventricular function. Changes in radionuclide indices describing left ventricular function in response to a therapeutic intervention must be interpreted in the light of these findings. PMID- 4040018 TI - Thyroid dysgenesis in monozygotic twins: variants identified by scintigraphy. AB - The unusual occurrence of neonatal hypothyroidism in monozygotic twins is reported. Scintigraphy demonstrated that permanent hypothyroidism in one resulted from an ectopic suprahyoid thyroid, while in the other, the transient hypothyroid state was associated with thyroid hemiagenesis. These findings suggest that the anomalies represent variants of the same developmental aberration. PMID- 4040019 TI - Does acute endoscopic evacuation improve the outcome of patients with spontaneous intracerebral hemorrhage? AB - A new endoscopic technique is presented, which allows burr hole evacuation of intracerebral hematomas under video control. Clot removal is achieved using a suction-irrigation system built in the 6-mm-diameter endoscope; in addition, an ultrasonic morcellement device has been developed for transendoscopic application. Small bleeding vessels in the hematoma cavity can be coagulated using a 1.5 mm Neodym YAG Laser microprobe introduced through the endoscope under visual control. A randomized prospective study has been started to raise again the question of indications for the surgical treatment of intracerebral hemorrhages, comparing medical treatment with the new surgical technique. PMID- 4040020 TI - cis-Diamminedichloroplatinum-induced hypomagnesemia and renal magnesium wasting. AB - Hypomagnesemia is a well-recognised complication of cis-diamminedichloroplatinum (DDP) treatment. We prospectively evaluated 50 patients with advanced malignant disease receiving DDP for the development of hypomagnesemia. Urinary magnesium excretion was measured in 24 patients. The mean serum magnesium fell from 0.79 mmol/l (normal 0.7-1.1 mmol/l) prior to therapy to 0.55 mmol/l 3 months after commencing DDP. All 50 patients had become hypomagnesemic by this time and 10% were symptomatic, requiring oral magnesium supplementation. At 6 weeks after commencing DDP only four patients had restricted urinary magnesium excretion to less than 1.0 mmol/day. The other patients clearly had inappropriately high levels of urinary magnesium excretion, suggesting that DDP may induce a renal tubular defect in magnesium conservation. Hypomagnesemia is a common complication of DDP therapy which in many patients is asymptomatic. Further, more detailed studies of renal magnesium handling are necessary to determine fully the effect of DDP on urinary magnesium excretion. PMID- 4040021 TI - The value of various forms of regional administration of cisplatin in the treatment of liver metastases in the rat. AB - Tumour growth was induced exclusively in the livers of 40 F1 WagRij/BN rats (eight groups of five rats each) by intraportal inoculation of a squamous cell carcinoma. Four groups were treated by infusion of cisplatin (to which the tumour was sensitive) for a total of three doses of 3 mg/kg body weight at 5-day intervals and one group served as control. Treatment was given systemically, via the hepatic artery, via the portal vein and the hepatic artery simultaneously, and via the portal vein. The untreated animals had a mean survival time of 119 days, as opposed to 211, 249, 192 and 239 days for the treated animals. The animals treated via the hepatic artery lived significantly longer on average (P = 0.035) than those treated systemically or via the portal vein. The combination of intraportal and intra-arterial infusion had no advantage over infusion via the hepatic artery alone. The route of administration does not appear to influence the general toxicity of cisplatin. PMID- 4040022 TI - Disorders of serum electrolytes and renal function in patients treated with cis platinum on an outpatient basis. AB - Two hundred and eighty-one patients received 927 doses of cis-platinum, generally on an outpatient basis, at 55 mg/m2 every 3-4 weeks. Mannitol and 2.2501 of hydration with saline and 5% dextrose plus NaCl and KCl were given in 3-4 hr. No case of acute renal failure ensued and when azotemia occurred (3.5% of patients) it was easily reversible and controlled. An abnormal level of one or more electrolytes was detected in 194 patients (69%) during chemotherapy. K+, Na+, Ca2+ and Mg2+ values usually decreased in serum after DDP administration, but their depletion seldom caused symptoms. Hypomagnesemia developed in 20% of patients, but was symptomatic in only 1%. cis-Platinum, at the doses utilized, is safely given to outpatients, with the hydration program employed. Serum electrolyte decrease during chemotherapy must be expected, and rapidly corrected when symptoms develop. PMID- 4040023 TI - Effects of long-term treatment of human carcinoma cells with interferon alpha. AB - Three tumor cell lines derived from human colon, urinary bladder and ovarian carcinoma were serially passaged in the continuous presence of human interferon alpha for extended periods of time. Phenotypic changes induced by interferon differed among these three cell lines. Thus interferon enhanced colon tumor cell aggregation but inhibited the aggregation of bladder tumor cells. The antiproliferative activity of interferon was more pronounced in bladder and ovarian cells than in colonic cells. However, the tumorigenicity of parental and cloned colon tumor cells injected i.p. or s.c. was markedly reduced by passage of the cells with interferon. Interferon treatment reduced the tumorigenicity of ovarian tumor cells when these cells were injected i.p. but not when injected s.c. The tumorigenicity of bladder tumor cells was not affected by interferon. PMID- 4040024 TI - Pulmonary embolism in patients receiving chemotherapy for advanced ovarian cancer. AB - The incidence of pulmonary embolism was examined in a series of 83 patients who had received chemotherapy for advanced ovarian cancer and ten embolic episodes occurred. The incidence of pulmonary emboli was highest in those patients who had gross bulk disease (greater than 10 cm diameter) before chemotherapy and occurred in 9/49 cases, with all six fatalities being in this group. Five of the six fatal emboli occurred within 1 week of the first course of chemotherapy. As the mortality rate from pulmonary emboli in patients with gross bulk tumour was 12% in this series, anticoagulation before initiating chemotherapy is suggested for this group of patients. PMID- 4040025 TI - Cisplatin plus vindesine in advanced breast cancer: a phase II trial of the EORTC Breast Cancer Cooperative Group. AB - This phase II clinical trial was conducted in a series of patients with advanced breast cancer, refractory to conventional chemotherapy. The therapeutic regimen consisted of a combination of cisplatin 100 mg/m2, given as a 24-hr infusion on day 1 and vindesine (VDS) 2 mg/m2, i.v. bolus on days 1 and 8. VDS injection was omitted on day 8 in patients with poor bone marrow reserves (prior extensive irradiation). Courses were repeated at 4-week intervals until documented disease progression. Among 46 evaluable patients, there were two complete and seven partial remissions for an overall response rate of 20%. These responses lasted for a median of 21 weeks (range 8-89 weeks). Remission rates according to the predominant metastatic site were as follows: soft tissue, 3/8 (38%); bone, 0/6 (0%); viscera, 6/32 (19%). Transient myelosuppression and gastrointestinal intolerance were almost universal. Renal function impairment and neurologic manifestations were frequently encountered but these adverse reactions were generally mild. Significant antineoplastic activity in far-advanced and heavily pretreated patients warrants further evaluation of this regimen at an earlier stage of the disease. PMID- 4040026 TI - Tolerance and physical dependence induced by dermorphin in rats. AB - Rats chronically implanted with osmotic minipumps in the left lateral ventricle were used to study the ability of dermorphin to produce tolerance and physical dependence. The development of tolerance, assessed by evaluating the time reduction of analgesia, catalepsy and rigidity, occurred in a dose-dependent fashion over a maximum period of 48 h. After 3 days of peptide infusions into the rat brain, the dependent state was established and was revealed by precipitating the withdrawal syndrome with intraperitoneal naloxone injections. Escape behavior, shaking, salivation and rhynorrhea were the main symptoms, qualitatively similar to those obtained in rats made dependent on morphine. Considering that dermorphin displays strong analgesic activity, the well-known combination of antinociception tolerance and dependence capacities of opiates also seems to be valid for dermorphin. PMID- 4040028 TI - Light and electron microscopical changes in the liver of mice following treatment with aminotriazole. AB - Light and electronmicroscopical alterations in the liver of mice were shown oral administration of aminotriazole. Intensity of damage depends on concentration. High dosage affects all inter- and intralobular portions. Presented light microscopical results show, next to an extreme hypertrophy of hepatocytes, well distinguishable nuclear deformations and increased pyknotic nucleoli. The cytoplasm contains numerous vacuoles and lipid droplets. Fine structural alterations after drug administration include defects on all cell organelles and membranes. Especially proliferations of smooth ER cisternae with simultaneous reductions of rough ER cisternae, increase of microbodies as well as numerous defects on mitochondria were obvious. Interpretations of the mode of action of aminotriazole is based on ultrastructural results and biochemical knowledge on this herbicide and compared with other toxicants. PMID- 4040027 TI - Rigidity and catalepsy after injections of muscimol into the ventromedial thalamic nucleus: an electromyographic study in the rat. AB - The cataleptic state induced by injection of the GABAmimetic drug muscimol into the rat's ventromedial thalamic nucleus (VM) was examined using an electromyographic (EMG) approach. Muscimol in doses up to 50 ng/0.5 microliter injected into the VM induced a tonic EMG activity in the gastrocnemius muscle which is considered to be a measure of limb rigidity. This tonic EMG activity was found to be dose-dependent, GABA specific and locus specific. By recording EMG signals from chronically implanted electrodes in awake, unrestrained rats it was shown that muscular reactions serving to maintain the animal's static equilibrium were intact in the state of VM induced catalepsy. However, animals were unable to initiate movements or locomotion even when they were forced by strong external stimuli. It was found that the animals' immobility was due to an inability to induce a phasic activation of their muscles whereas tonic activation still occurred. It is concluded that the rat's VM is part of a neuronal chain conducting information relevant for the expression of limb rigidity, the VM is involved in the central mechanisms responsible for the phasic activation of a set of muscles. PMID- 4040029 TI - Studies on the mechanism of macrophage cytotoxicity. AB - The interactions with tumor target cells of resident and BCG-activated murine peritoneal macrophages (M phi) as well as of BCG-activated M phi additionally stimulated by a lymphokine-like factor were investigated in order to get some insight into the cytolytic process mediated by activated M phi. The lymphokine like factor enhancing the cytotoxicity of BCG-activated M phi (MCF) was isolated and partially purified from cell-free fluid of rat Zajdela ascites hepatoma. M phi cytotoxicity was determined by a modified 51Cr release assay. Scanning and transmission electron microscopic findings suggested a two-step mechanism of target cell lysis: a first step of specific attachment of processes of M phi on the target cell surface and a second step with transport of lysosome-like vesicles to the target cells obviously with liberation of these vesicles in the immediate vicinity of target cells resulting in a local accumulation of cytolytic substances. This interpretation was supported by findings after treatment of interacting effector and target cells with amphotericin B and bestatin which substances were modifying M phi cytotoxicity. MCF caused only an augmentation of M phi cytotoxicity without qualitative differences to the cytolytic action of merely BCG-activated M phi. PMID- 4040030 TI - Redox status of cultured fibroblasts. Possible relations with specific catabolic rates of proteoglycans. AB - In cultured embyonic rat fibroblast the cytoplasmic NAD/NADH ratio was determined from the lactate/pyruvate ratio under acidic, hypoxic and lactic acid-rich conditions. RESULTS AND CONCLUSIONS: The NAD/NADH ratio is reduced when the lactate concentration increases at pH 7.4 with and without hypoxia. At pH 6.6 this ratio is not reduced by lactate in normoxia: Conditions of aerobic glycolysis did not increase NADH. The NAD/NADH ratio was strongly lowered at pH 6.6 by lactate plus hypoxia. At low cell density this condition of hypoxic glycolysis is correlated with the increase of the specific activities of CS- and DS-proteoglycans (DS much greater than CS). But only the CS concentration was increased. Conditions of aerobic glycolysis at low cell density caused a moderate increase of both the specific activity and concentration of DS. The different regulation of the turnover of CS- and DS-proteoglycans is suggested to be based on their different synthetic capacities (CS greater than DS) on the one side and on the effect of specifically acting proteoglycanases on the other side. Maximal degradation of proteoglycans seems to be stimulated by NADH-activated proteases, supposedly thiol proteases. Lower degradation seems to be effectuated under non reductive acidic conditions. Both these types of degradation seem stronger to affect DS-proteoglycan. Some neutral proteases seem stronger to affect CS proteoglycan. Improved oxygen supply might reduce the CS concentration in proliferating tissue, such as in chronic inflammation, and thus reduce this process. PMID- 4040031 TI - Biochemical and histochemical studies on alkaline phosphatase in normal and dystrophic muscle. AB - In muscles from dystrophic mice the activity of alkaline phosphatase is 50-75% higher than in their control littermates. In the dystrophic animals all muscle fibres show strong enzyme activity. It is suggested that during dystrophy amounts of an already existing muscle alkaline phosphatase are produced rather than that a synthesis of a new isoenzyme should be initiated. PMID- 4040032 TI - Electron microscopic study of liver fibrosis associated with diabetes mellitus. AB - Electron microscopic studies of 13 cases of liver fibrosis associated with longstanding diabetes mellitus are presented. Comparing the centrilobular and periportal areas of the lobules there appeared to be a difference in the amounts of glycogen, fat, collagen and the character of mesenchymal cells. Centrilobularly, collagenization of sinusoids and pericellular accumulation of fibres appeared with the destruction of hepatic cells. In the periportal regions there was an accumulation of Kupffer's cells with active phagocytosis and centrally of Ito's cells and fibroblasts. The presented alterations were similar to the central pericellular fibrosis described in connection with morbid obesity. Despite the large number of available data on liver fibrosis there is still no satisfactory explanation for the pathomechanism of centrilobularly developing fibrosis. PMID- 4040033 TI - On the varying degrees of cancerogenicity of modified gastroentero-anastomoses. AB - In our serial investigations we checked the incidence of carcinomas in different cases of anastomoses and resections on the rat stomach. Moreover we supervised the regenerative behaviour of the gastric mucosa by means of in vivo autoradiography using 3H-thymidine. The experimental animals were divided into 5 treatment groups. We carried out gastroenterostomy on 9 animals (group I), Billroth's second operation on 7 animals (group II), a duodenal ligature, pyloroplasty and gastro-enterostomy with Braun's anastomosis on 10 animals (group III), a pylorectomy as well as Roux's gastro-enterostomy on 10 animals (group IV) and a laparotomy on 11 control animals (group V). The greatest tumour onset rates with 4 adenocarcinomas each were observed in the groups I and III, and with 5 carcinomas in group II 7 months after the operations. The labelling indices obtained autoradiographically are such that glandular hyperplasias with indices of over 13.3 p.c. and carcinomas with values of about 24.7 p.c. enable an unambiguous distinction from the values of the sound glandular gastric mucosa. Entero-gastric reflux is discussed in this paper as the most important cause of carcinogenesis. PMID- 4040034 TI - Influence of native collagen on the cell cycle. AB - The influence of native collagen-solutions on the cell cycle of human-fibroblasts was investigated. The results point out that the phase of cell-specific function is distinctly lengthened to the debit of a reduced rate of mitosis. That seems to be desirable, because the cells of the implantation-layer would produce more rapidly and augmentedly their cell-specific product--usually collagen--and incorporation of the implanted material would occur quite earlier. This effect seems also to be responsible for the promotion of granulation of "Dermodress", a fleece of collagen I for temporary covering of debrided areas (5). PMID- 4040035 TI - The role of the substantia nigra on the rage reaction elicited by hypothalamic stimulation, in the cat. AB - The effects of substantia nigra stimulation on the rage reaction evoked by hypothalamic activation were studied. The reference value of the rage reaction was the latency of the hissing, which was constant in all animals when hypothalamic stimulation was performed with the same parameters. Simultaneous activation of substantia nigra and hypothalamus determined a significant decrease in hissing latency. The influence of the substantia nigra on the affective components of the aggressive behavior is underlined. PMID- 4040036 TI - Detection of granuloma-associated plasminogen activator in experimental murine schistosomiasis. AB - Hypersensitivity granulomas induced by infection with Schistosoma mansoni were isolated from the livers of BALB/c mice after 7, 8, 10, and 12 weeks. The parasite egg-granulomas were sequentially extracted with a Tris-buffered saline (soluble fraction) and 2 M KSCN (bound fraction). Fibrinolytic enzyme activity measured with both synthetic substrates and fibrin plates demonstrated an elevated level of plasminogen activator activity in the bound fraction 7-8 weeks after infection when mature granulomas first began to appear, followed by a gradual decrease 10-12 weeks after infection. An electrophoretic enzymography technique revealed multiple molecular species of plasminogen activator at Mr = 95K, 74K, 60K, 45K, and 24K. The bands with Mr = 45K and 24K were found compatible with the electrophoretic pattern of macrophage-plasminogen activator. When the granulomas reached maximum size after 10 to 12 weeks, the plasminogen activator with 45K and 24K diminished, while plasminogen activator activity at Mr = 95K, 74K, and 60K remained unchanged suggesting the presence of both vascular and tissue types of plasminogen activators. There was no urokinase-type plasminogen activator detectable in granulomas at any time. In the soluble fraction no enzymatic activity was found, whereas regulating inhibitor activity for plasminogen activator was consistently detectable. PMID- 4040037 TI - Interactions of the human red cell membrane tyrosine kinase with heparin. AB - Heparin interacts with protein kinases in various ways; the different patterns of behavior of heparin towards protein kinases contributes to the characterization of these enzymes. We studied the interactions between heparin and a new type of tyrosine kinase extracted from the normal human red cell membrane. We found that heparin inhibited kinase activity by competition with ATP. Furthermore the interaction of heparin with the red cell membrane tyrosine kinase allowed us to use heparin-agarose chromatography as a step towards tyrosine kinase purification. PMID- 4040039 TI - Massive spontaneous superovulation in a sexually mature pig. AB - Ovulation of 97 follicles was recorded in a gilt that had not received any hormonal treatment, and circumstantial evidence adduced for a rapidly proliferating tumour of the adenohypophysis. A lesser degree of superovulation had occurred in the previous oestrous cycle, whilst the rate of follicular development in the current cycle was exceptional. None of the 93 eggs recovered from the oviducts was a primary oocyte, but three were polyspermic pronucleate eggs. The most advanced stage of embryonic development was that of 4-cells. Such a degree of spontaneous superovulation has never been observed before during careful examination of more than 1200 pairs of ovaries from gilts in the same herd. PMID- 4040038 TI - Further evidence that big,big prolactin is preferentially secreted in women with hyperprolactinemia and normal ovarian function. AB - The heterogeneity of human serum prolactin (PRL) in 12 women with hyperprolactinemia and different derangements of the hypothalamic-pituitary ovarian axis was studied. The patients were subdivided into three groups: four women with hyperprolactinemia and normal ovarian function (group I), four women with hyperprolactinemia associated with sporadic endometrial bleedings and a positive progestin test (group II), and four women with amenorrhea and a negative progestin test (group III). Gel filtration chromatography of serum samples from patients in group I revealed in three of them that most (80%) of their immunoreactive PRL eluted as big,big PRL (Mr greater than 100,000); whereas the rest of the patients, including those from groups II and III, exhibited a distribution pattern similar to that obtained in normal menstruating women. All PRL species had similar affinities for the antibody, as disclosed by the slopes generated in dose-response curves. These results indicate that ovarian function in hyperprolactinemia might be dependent upon PRL heterogeneity and suggest that big,big PRL may have, under in vivo conditions, a low degree of biologic activity. PMID- 4040040 TI - Reconstitution of a partially purified Na+-dependent D-glucose transport system from rat jejunal brush border membranes. AB - The Na+-dependent D-glucose transport system of rat jejunal brush border membranes was partially purified and reconstituted into functional proteoliposomes. Brush border membrane vesciles isolated from villous cells were first extracted with 0.3% cholate to remove extrinsic proteins and the insoluble residual pellet was reextracted with 1.2% cholate. The 1.2% cholate-extracted soluble fraction was then further purified by hydroxylapatite and Concanavalin A affinity chromatography in tandem. When the HLP-unadsorbed-ConA-unadsorbed fraction was reconstituted into proteoliposomes, it showed a characteristic Na+ coupled, phlorizin inhibitable, D-glucose transport activity that was 3 fold higher than that of the reconstituted proteoliposomes of the 1.2% cholate extracted fraction. This partially purified fraction also displayed the simplest polypeptide composition pattern among all the membrane fractions analysed in SDS polyacrylamide gels. PMID- 4040041 TI - Opposite effects of ethanol on the activation of adenylyl cyclase in human corpus luteum membranes. AB - The influence of an acute exposure to ethanol on adenylyl cyclase activity in membrane fractions prepared from human corpus luteum was investigated. Ethanol up to a concentration of 5% (v/v) was without effect on basal luteal adenylyl cyclase activity, but markedly potentiated stimulation of NaF and hCG in a dose dependent manner. In contrast, ethanol progressively inhibited forskolin stimulation at the same range of ethanol concentrations. Maximal NaF and hCG responsiveness of adenylyl cyclase activity was observed at 5% ethanol and reached values 80% and 100% higher than controls without ethanol, respectively. However, at the same ethanol concentration, forskolin-stimulated enzymatic activity was reduced by 40% relative to controls. Equilibrium binding studies involving [125I]hCG interaction with luteal membranes in the presence of the concentration of ethanol showing maximal hCG responsiveness indicated that ethanol slightly affected (15% increase) the hCG binding compared to controls, without any appreciable change on the Kd for the hormone. This minor effect of ethanol on gonadotropin binding sites contrasted greatly with the extent at which ethanol maximally potentiated the gonadotropin-stimulated adenylyl cyclase. GTP was found to be less effective than GMP-P(NH)P in sustaining ethanol potentiation, suggesting that ethanol is unlikely to act by inhibiting GTPase activity. These data indicate that the acute effects of ethanol inhibit forskolin stimulated adenylyl cyclase at concentrations potentiating stimulatory effects of NaF and of hCG, and that the synergistic interaction of ethanol and gonadotropin stimulation of adenylyl cyclase is, at least in part, due to an increase in the functional coupling of the occupied hCG-receptor complex with the components of the enzyme system. PMID- 4040042 TI - [Effect of intense mental load on night sleep]. PMID- 4040043 TI - [Congenital heart defects as a cause of still birth and infant mortality]. AB - Among 4,686 still-births and children died from 0 to 1 a in the German Democratic Republic in 1979 there were 307 (6.6%) isolated congenital heart diseases. We only analyzed 294 died infants. The first 5 diagnoses were: Hypoplastic left heart (all infants died within the first 28 d) 9.9%, Ventricular septal defect 9.9%, Transposition of great vessels 8.8%, Coarctation aorta 7.1%, Common truncus arteriosus 5.8%. The most important results are an interesting frequency with advancing years of mothers (3.4% in 10,000 mothers of live-births aged 16 a and less to 20.6% at the age of 40 a and over (see Fig. 1), 13% premature children (under 37 weeks of gestation), 23% children under 2,500 g birth weight, 55% boys and 45% girls. 80% of the above 294 infants died within the first 3 months. PMID- 4040044 TI - [Nonpuerperal mastitis]. AB - The medical history of 37 women with nonpuerperal mastitis, who had been treated between January 1980 and July 1983 at the Dept. of Obstetrics and Gynaecology of the University of Tubingen, was reviewed because of the increasing prevalence of this disease. Defined by different history and clinical symptoms, two groups of patients were seen: 25 women with acute nonpuerperal mastitis and 12 women with chronic recurring nonpuerperal mastitis. The average age of the patients was 30 years. The inflammation was located mostly subareolar and around the nipple. The main symptoms were pain, erythema and swelling, in acute cases accompanied by fever and abscess formation. This process was strongly related to the interval between the onset of symptoms and the initiation of treatment. Anaerobes and Staphylococcus aureus could be cultured mainly from women with acute nonpuerperal mastitis. In females with chronic recurrent mastitis, mostly anaerobes were found. Women were treated with a prolactin inhibitor (bromocriptine), if abscess formation, leukocytosis or fever were absent. In patients with leukocytosis and/or fever this regimen was combined with antibiotics. Abscesses were treated surgically, in some cases in combination with prolactin inhibition and antibiotic administration. The results show that an early conservative treatment is important to prevent abscess formation. It seems that this treatment can reduce the rate of recurrences. PMID- 4040046 TI - The influence of physical exercise on growth and sexual maturation in young female rats. AB - This investigation deals with the influence of physical activity on the growth and sexual maturation of weanling female Wistar rats. It involves three groups of rats, namely an intensively trained group (n = 45), a moderately trained group (n = 49) and a nontrained group (n = 49). The trained groups were forced to perform physical exercise from the age of 15 days on, on a treadmill. Within the intensively trained group, exercise was increased by increasing the speed and grade of the treadmill. The exercise of the moderately trained group was held constant. A delay in the day at vulva opening, indicating sexual maturation is seen in the extensively trained group in comparison with the moderately trained and nontrained group. The average body weight at the day of vulva opening is the same in all groups. However, the correlation coefficient between day at vulva opening and body fat mass is not significant. No differences in the body- and tail-length growth can be detected between the groups. A delay in the sexual maturation due to stress can be rejected since the open fields results registrating stress parameters, as obtained from the various groups of animals, are in general not significantly different between the intensively trained and moderately trained as well as nontrained groups. This investigation shows evidence that intensive physical exercise from young age on, causes a delay in sexual maturation, although it has no influence on the body- and tail length growth. PMID- 4040045 TI - Ultrastructural investigation of extracellular structures in subcapsular white corrugated cataract (anterior capsular cataract). AB - Electron microscopic investigations were performed on six extracted lenses from patients undergoing operative treatment of subcapsular white corrugated cataract. The lens capsule itself was unaltered. There was a pronounced extracellular space under the capsule. In this area collagenous aggregations equivalent in size to collagenous fibres and fibrils could be seen. Collagenous microfibrils and delicate microfilaments were also present. The latter could be observed with and without cross-striations. The fibrous structures are distinguished by considerable variations in shape and diameter. The precursor stages of these fibrous materials are produced by myofibroblast-like cells, probably derived from the lenticular epithelium. PMID- 4040047 TI - Animal growth during liberation from appetite suppression. AB - Superalimentation (SA) of swine at 120% (ad libitum = 100%) for 23 days elicited a 40% greater gain of body mass (P less than .005) than littermate control (C) pigs. The accretion of lean and fat tissues during this excess and rapid growth were about the same as if the animal were allowed to attain the same weight over a longer period by conventional feeding practices. Superalimentation is defined as feed intake distinctly in excess of normal voluntary intake on a grams-dry matter-per-kilogram-body-weight basis. The substantial body mass response shows that growth is limited by a lack of nutrient intake (appetite) during normal ad libitum feeding. Either digestion-absorption processes are not saturated during normal feed intake or digestion and absorption capacities are enhanced during excess food intake; furthermore, either cellular hyperplasia or hypertrophy are not regulated by inherited neuroendocrine factors or cellular growth is somehow released from neuroendocrine regulation during periods of excess circulating nutrients. The overall gain efficiency (kg total gain per kg total alimentation dry matter) during superalimentation was slightly improved (7.3%) but was not significant. Efficiency of the differential gain (delta gain/delta dry matter intake; delta = SA-C) was 25% higher than the overall gain efficiency of the C pigs (0.374 vs 0.300 kg/kg) and suggests that the additional nutrients may have been utilized for growth with greater efficiency than nutrient consumed ad libitum. PMID- 4040048 TI - Anatomical and functional changes in the lower urinary tract after radical hysterectomy with lymph node dissection as studied by dynamic urethrocystography and simultaneous urethrocystometry. AB - Seventeen urologically healthy women undergoing standardized radical hysterectomy with lymph node dissection for stage I carcinoma of the cervix were evaluated urodynamically before, immediately after, and 1 year after surgery, by dynamic videourethrocystography and simultaneous urethrocystometry. The surgical technique had been developed in order to preserve as much of the nerve and blood supply to the bladder and urethra as possible. Major dysfunction was found in the early postoperative state, but the lower urinary tract almost always regained its preoperative functional status in the course of approximately 1 year. There were no long-lasting functional changes which interfered with daily life, although small static and dynamic changes were observed. The changes occurred chiefly above the urogenital diaphragm. The results of the two urodynamic examinations, each giving different information, corresponded well. Used together they gave a more complete picture than used separately. Dynamic videourethrocystography offered information about the function of the bladder and urethra which could not be obtained by urethrocystometry alone. PMID- 4040049 TI - Complications from intraperitoneal radioactive phosphorus in ovarian malignancies. AB - A retrospective study of the use of phosphorus-32 in the treatment of 73 cases of ovarian malignancy to evaluate the safety and morbidity is presented. The surgically confirmed major complication rate with P-32 alone was 4 of 54 cases (7.4%). The addition of external radiation raised the surgically confirmed complication rate to 4 of 19 cases (21%) and with the addition of those diagnosed and treated only medically the rate rose to 8 of 19 cases (42%). In Stage I cases, Grades 1 and 2, there was only 1 death in 26 patients (96%), whereas for Grade 3 tumors only 6 of 12 patients (50%) were living at the end of 2 years. PMID- 4040050 TI - The use of methylprednisolone and metoclopramide in control of emesis in patients receiving cis-platinum. AB - cis-Platinum is a chemotherapeutic agent with benefits often limited by the severe gastrointestinal reactions it produces in nearly all patients. Persistent anorexia, nausea, and vomiting may continue for days after therapy and are poorly controlled by conventional antiemetics. Patients at times refuse continuation of cis-platinum chemotherapy because of these severe gastrointestinal side effects. Intravenous methylprednisolone (Solu-medrol) as well as intravenous metoclopramide (Reglan) have been shown effective in the treatment of chemotherapy-induced nausea and vomiting. This randomized, double-blind study is a comparison of the efficacy of Solu-medrol vs Reglan, as well as, the combination of Solu-medrol and Reglan in the prevention of cis-platinum-induced nausea and vomiting. In this study patients receiving Reglan had better protection from vomiting than patients receiving Solu-medrol (P = 0.0564). Patients receiving the combination of Reglan and Solu-medrol had better protection from vomiting than patients receiving Reglan alone (P = 0.0332), or patients receiving Solu-medrol alone (P = 0.0010). Finally, older patients experienced less vomiting than younger patients, regardless of the anti-emetic drugs used (P = 0.0730). PMID- 4040051 TI - Immunoglobulin-producing cells in lymphatic tissues of germfree and conventional rabbits as detected by an immunofluorescence method. AB - Lymphatic tissues of GF and CV rabbits were observed. No cells producing IgA and IgM antibodies were detected in appendix, sacculus rotundus, ileum terminale and thymus of GF rabbits. IgA cells were found in lymph nodes of GF rabbits. PMID- 4040052 TI - The X----Y----Z scheme after 23 years. AB - Mathematical modelling of the course of the immune response is undoubtedly one of the most progressive and most promising areas of modern immunology. Mathematical models (along with computer programs) can be taken as "the only means of thoroughly testing and examining a large and intricate theory" (Partridge et al. 1984). The first phase of construction of mathematical models is the formulation of assumptions based on the knowledge of the facts to be modelled (manifested usually in a scheme of the presumed course of the modelled process). The first mathematical models of immune response were based on the hypothesis of a two stage differentiation of cells participating in the humoral response, published in Prague 23 years ago (Sercarz and Coons 1962; Sterzl 1962) and illustrated by the X----Y----Z scheme. Many contemporary mathematical models still stem from this scheme which undoubtedly fits the fundamental data concerning the immune system. PMID- 4040053 TI - Proceedings of an International Workshop on Irritation Testing of Skin and Mucous Membranes. 3-5 April 1984, Kartause Ittingen, Switzerland. PMID- 4040054 TI - Ethical considerations in toxicology. AB - Since most of the research necessary for the safety evaluation of chemicals requires the killing of laboratory animals, toxicologists are faced with an ethical conflict between their professional duties and the interests of the animals. In the past, the protection of consumers against chemical injury was considered to be of the greatest importance, and society approved of all efforts to detect even the slightest hazards from man-made and environmental chemicals. In recent years, toxicologists have become aware of their ethical responsibilities not only for the safety of the human population but also for the welfare of the animals. They have begun to review the classical toxicological procedures critically and now require that the maximum amount of relevant information is obtained from the smallest number of laboratory animals. Toxicologists have also become aware of the alternative methods that permit the investigation of toxicological responses in unicellular organisms and cell cultures. The problem of testing chemicals for irritant properties on skin and mucous membranes is an excellent example of how concern for animals has generated a range of original and imaginative research leading not only to a reduction in the use of animals but also to a more efficient and scientific approach to an important health problem. PMID- 4040055 TI - The Draize test--motivations for change. AB - The use of animals in research and testing is an issue of increasing public concern, with many people convinced that it is unjust to expose any sentient and unconsenting individual to suffering, or risk of suffering, when the only potential benefit would be to others. Such ethical considerations make the introduction of alternative forms of research and testing an urgent priority. In the case of the Draize eye irritancy test, however, scientific considerations superimpose ethical motivations for change, because the procedure is also unsatisfactory on scientific grounds. After concerted pressure from animal welfare groups throughout the world, several laboratories are now investigating humane and more scientific replacements for this test, with encouraging results. Some of the techniques being used have long been available, even before the introduction of the Draize test itself in 1944. This shows what could be achieved today, in other areas of animal testing, assuming the necessary imagination, motivation and resources. Focusing the scientific mind on alternative methodologies is expected not only to benefit science and the animals, but to protect the public more reliably as well. PMID- 4040056 TI - Acute irritation tests in risk assessment. AB - The two most important elements in assessing the risk of topical injury from a chemical are its biological properties, in the context of skin and mucous membrane damage, and the likelihood and likely nature of topical contact with the chemical. Appropriate biological tests in model systems should be based on the probable circumstances of exposure. Topical contact takes place under two distinct sets of circumstances--intentional and accidental. Chemicals that are intended to come into contact with skin and mucous membranes include cosmetics and dermatological preparations. For such compounds the frequency and extent of skin contact is predictable and any irritant effects are unacceptable. The absence of irritant effects is established by testing in human volunteers or experimental animals. Since animal skin and mucous membranes are more susceptible to irritants than those of man, the amounts or concentrations tested need not be greater than those intended for human use. It is hoped that validated alternatives to animal models will soon be available. For household or industrial chemicals where skin and/or mucous-membrane contact occurs accidentally, topical contact should generally be avoided. In such cases the objective of irritancy testing should be to establish which compounds are particularly irritant and therefore need extra care in handling. We are convinced that this latter objective can be achieved by simpler and less cruel tests than the Draize eye irritation test. PMID- 4040057 TI - Acute skin toxicity reactions in man--tests and mechanisms. AB - There is increasing concern to avoid toxicity reactions from materials that come into contact with the skin. In this paper the mechanisms underlying the commonest type of cutaneous toxicity, i.e. the dermatitis reaction, are discussed. The various tests that may be used to predict human cutaneous toxicity are reviewed, with emphasis on in vivo human toxicity tests. It is concluded that preliminary testing of potentially toxic materials should be conducted in vitro or, until such tests are available, in small mammals, but that definitive tests of finished products should be performed in vivo in man. PMID- 4040058 TI - Overview of animal test methods for skin irritation. AB - Determining the irritant effects of chemicals in experimental animals provides the public with information on and protection against possible hazards that may arise from exposure of the human skin. Furthermore, the data obtained are used for registration and classification purposes. This paper reviews the methods proposed in the most important guidelines (OECD, EEC and FIFRA guidelines) and points out the critical experimental points. It shows that the introduction of OECD Guideline No. 404 can lead to a reduction in the number of test animals used for skin irritation testing. PMID- 4040059 TI - Assessment of the validity of animal techniques in eye-irritation testing. AB - Since its introduction 40 years ago, the Draize test for eye irritancy has remained largely unchanged in spite of long-standing controversy over ethical and scientific aspects. It is suggested that deficiencies in the data derived from the test which arise from defects in the basic test design, cannot be fully compensated for by supplementary methods or data handling schemes. As a limited amount of in vivo testing is still required, attempts should be made to improve the method by attention to the scientific principles involved, using current knowledge of inflammatory mechanisms. Proper attention to design and approach will help to resolve both the scientific deficiencies in the test and help to overcome the reservations that are currently felt with regard to the ethics of the test. PMID- 4040060 TI - A more realistic animal technique for predicting human eye response. AB - The FHSA test (CPSC, 1981) for eye irritation in rabbits overpredicts the likely response of the human eye. Nineteen different chemicals, mixtures or solutions that had different degrees of recognized irritancy potential to the human eye were tested in albino rabbit eyes at dose volumes of 0.003, 0.01, 0.03 and 0.1 ml. The material was administered directly onto the rabbit cornea, without forced closing of the eyelid and without rinsing. A dose volume of 0.01 ml most often gave results that were consistent with information on effects of human eye exposures. The report of this work (Griffith et al. Toxic. appl. Pharmac. 1980, 55, 501) recommended that this more realistic 'low-volume' technique (0.01 ml of test material) should replace the FHSA test (0.1 ml of test material). The recovery times of human eyes after accidental exposure to consumer products in the USA, either during manufacture or in incidents involving consumers, were compared with the number of days-to-clear of rabbit eyes (tested in either the FHSA or the low-volume test) or monkey eyes exposed to the same products. Over 500 incidents involving human eyes (over several years) are included in the review. All three animal techniques are shown to overestimate the severity of the human eye response, the FHSA method being the worst in this respect. Only the results of the low-volume rabbit test show a statistically significant correlation (P less than 0.05 r greater than 0.5) with human experience. It is recommended that this low-volume test in rabbits should replace the FHSA test as the internationally agreed test for eye-irritancy potential because it correlates best with the response of the human eye. PMID- 4040061 TI - Registration requirements within the German Federal Health Office. AB - Public health authorities responsible for consumer protection in connection with the use of chemical products are faced with several conflicting requirements. In addition to the primary requirements of protecting human health and assessing the balance between benefits and risks, the authorities are faced with the need to identify appropriate tests, to avoid unnecessary testing in experimental animals, to adapt existing test guidelines in the light of new technological and scientific developments and to make optimal use of the facilities and expertise available. Among the measures being taken by the German Federal Health Office to resolve these difficulties, particularly in connection with the testing of chemicals for skin and eye irritancy, are the evaluation of alternatives to animal tests, the encouragement of more effective screening and use of existing test results, promotion of the international exchange of test data, and support for proposed changes in the use of the Draize test. PMID- 4040062 TI - Animal protection and toxicity testing regulations. AB - Safety testing illustrates a very real ethical dilemma between our moral obligations to protect humans and to protect animals from harm. The pragmatic approach to resolving this conflict is to pursue the 3 Rs of Replacement, Reduction and Refinement. Safety tests set out in regulation protocols often conflict with this ethic, being wasteful in numbers of animals used, having unnecessarily severe end-points and resulting in duplication. Suggestions for refinement of these tests are discussed. It is concluded that such refinement could lead to the generation of more meaningful data, thus improving both animal protection and human safety. PMID- 4040063 TI - Modification of the Draize eye test for the safety testing of cosmetics. AB - Until alternatives to the Draize test have been developed and shown to be adequate for assessing the safety of cosmetic products, modification of the existing method to reduce the numbers of animals required and the severity of the effects induced is of great importance. In the testing of cosmetic products, comparison with already known products plays an important role. Tests to demonstrate whether a new product is better or less well tolerated than a known one can be carried out with concentrations that are only slightly irritating. A decrease or increase in effect is clearly identifiable with these relatively low concentrations, and allows the product to be appropriately assessed. PMID- 4040064 TI - Changing concepts of ocular irritation evaluation: pitfalls and progress. AB - A series of studies has been carried out to evaluate methods of modifying existing ocular test protocols with the aim of reducing the numbers of animals used and lessening the severity of the response with the minimum effect on the predictive value of the tests. Initial studies showed that when the dose administered is reduced from 100 to 10 microliter, the severity of the response is reduced but the rank order of severity of a series of test compounds is unchanged. This series of studies also demonstrates that the greatest source of variability in obtaining irritation scores is in the rabbit population and that the numbers of rabbits used per test can be chosen on the basis of the required degree of accuracy. In a related study it is shown that direct corneal application of the test material (10 microliter) increases the corneal response but has no effect on the conjunctival response in comparison with reactions after application in the conjunctival cul-de-sac. Finally, a retrospective study was performed to determine whether severe skin irritation is predictive of a similar level of response in the eye. Of 60 compounds known to be severe skin irritants, only 39 are severe eye irritants whereas 15 are mild to non-irritants. The remainder were found to cause moderate responses in the eye. These data demonstrate that existing ocular irritation test protocols can be modified to use fewer animals under less extreme conditions without significant compromise of predictability. However, dermal irritation, determined using current test protocols, does not appear to be directly predictive of ocular irritation potential. PMID- 4040065 TI - The mouse intradermal test, a well-established and reliable model in skin tolerance testing. AB - The intradermal test in mice is a valuable model for assessing dermal tolerance to chemical substances. The test material is administered intracutaneously to hairless or depilated mice through a fine syringe, the animals are killed after 24 hours and the treated skin is removed, dried and assessed for reaction area, erythema and oedema. The skin fragments can be preserved as a record of the findings. While direct transfer of the findings from mouse to man is likely to be misleading, the test is well suited to comparative studies. Moreover it requires only small numbers of mice. PMID- 4040066 TI - Quantitative assessment of irritation in the mouse skin test. AB - Intracutaneous injection of aqueous solutions of topically irritant substances into the skin of juvenile mice creates a persisting oedema, the strength of which can be assessed by the number of wrinkles formed on reefing the skin at the site of injection. An algorithm is used to transform the number of wrinkles, recorded just before and 2.5 and 6 hr after the injection, into the intensity of the oedematous reaction. This quantity, which does not depend on subjective assessments graded on an arbitrary scale, is reproducible and has been judged to be relevant to the prediction of irritancy likely to arise from accidental contact of substances with mucous membranes. PMID- 4040067 TI - An approach to the development of in vitro toxicological methods. AB - Over the last few years there has been increased societal pressure on the one hand and self-generated scientific pressure on the other to develop new and better in vitro techniques for the evaluation of the safety of commercial products. In vitro methodology addresses four major areas within toxicology. It provides the basic science of the discipline with new information. In acute toxicity testing, it can provide alternatives to current approaches, e.g. the Draize irritation tests. In the area of chronic toxicity testing, it will allow us to define the mechanisms associated with organ specific insults. In the area of risk assessment, the combined knowledge obtained by superior methods will allow us to assess risk more accurately. The results of studies on alternatives to the Draize irritation tests being carried out at or supported by The Johns Hopkins Center for Alternatives to Animal Testing will be reviewed. PMID- 4040068 TI - The FRAME interlaboratory programme on in vitro cytotoxicology. AB - FRAME (the Fund for the Replacement of Animals in Medical Experiments) has established a research programme in collaboration with four research centres and a number of industrial companies, to determine whether cell cultures can reliably be used to replace live animal procedures in routine tests on the relative acute toxicities of chemicals. Following the development of the test protocol, initial trials were carried out to establish intralaboratory and interlaboratory reproducibility and the criteria for choice of cell types, end-points and metabolizing systems. A set of coded chemicals is being collected for use in blind trials and summaries of existing knowledge of the in vivo toxicity of these compounds are being produced. More recently, FRAME has established an international validation scheme for in vitro alternative methods. PMID- 4040069 TI - An in vitro epidermal slice technique for identifying chemicals with potential for severe cutaneous effects. AB - We have developed an in vitro model, using epidermal slices, to identify skin corrosive potential. Such potential has been correlated with the ability to lyse stratum corneum, indicated by a lowered electrical resistance of the skin slice. Using 41 corrosive and 22 irritant chemicals, a comparison of in vitro and in vivo classifications has shown that this in vitro technique identifies corrosive agents with high precision. Therefore the model has considerable potential as a prescreen to conventional animal tests and, unlike in vivo screening tests, can provide both objective and quantifiable data. PMID- 4040070 TI - The use of cell and organ culture from the respiratory tract for testing chemicals. AB - For the toxicity testing of compounds using tissue from the respiratory tract, three types of in vitro cell or tissue culture systems are being developed from foetal Syrian hamster respiratory organs on day 15 of gestation. The first system, early-passage cell cultures of a mixed population obtained from foetal lungs, has been used frequently for the study of in vitro cell transformation. The clonal culture technique using these cells permitted the semi-quantitative determination of the toxicity of poly- or heterocyclic hydrocarbons in terms of the reduction in the number of surviving colonies. The second system, an explant culture technique using foetal tracheae, demonstrated the induction, by polycyclic hydrocarbons, of alterations such as hyperplasia, epidermoid metaplasia or dysplasia of mucociliary epithelia. The third system uses the cells of a permanent clonal epithelial cell line established from the foetal lung. These cells differentiated into a mucus-producing cell type in a medium supplemented with vitamin A and hormone. In order to observe general aspects of toxicity in these cells, they were exposed first to model substances such as sulphuric acid and potassium dichromate. After 24 hr of post-exposure incubation, the activities of membrane-bound and cytosolic enzymes, the amount of sialic acid released into the medium and cell survival were measured. Based on the results obtained so far, the potential value of each system is discussed. PMID- 4040071 TI - The penetration of detergents into adult and infant eyes: possible hazards of additives to ophthalmic preparations. AB - In studies of surfactant penetration into the eye, radiolabelled detergent was found to penetrate the rabbit cornea, to accumulate readily in ocular tissues and to be released slowly. Repeated applications led to increasing binding of the detergent. Permeability, ocular and systemic uptake and retention were all greater in juvenile than in adult rabbits. Preliminary tests of the effects of surfactants on ocular cells in vitro using concentrations found in vivo, suggest that some low-level effects might occur, particularly in juveniles. PMID- 4040072 TI - Interpretation of cell toxicity data for the estimation of potential irritation. AB - Three cytotoxicity assays were evaluated using 57 chemicals of various classes (inorganic and organic metal salts, solvents, detergents, reagents, drugs) which have widely different mechanisms of cytotoxicity. Baby hamster kidney fibroblasts (BHK-21/C13) and early (Keller) and late (MRC-5) passage human fibroblasts were used to measure cell detachment, cloning efficiency, and growth inhibition under subconfluent culture conditions. For the majority of chemicals, for which comparisons were made, the ranking order was roughly the same in all three tests and with all three cell types. However, for some chemicals specific growth effects could either be detected or excluded because the relationship between the data from the detachment assay and that from one of the growth assays was characteristically altered. The ranking order resulting from our in vitro data correlated better with threshold limit values for human workroom air (TLV/TWA) than with LD50 values (rat, oral). Correlations with data from Draize skin and eye irritation tests were not determined since the available in vivo values were derived using various different scoring systems. However, when our in vitro data were used to divide the chemicals into three crude classes, (i) non-irritant, (ii) mild to moderate irritant, or (iii) strong irritant or corrosive, and the results were compared with the known irritation potential for skin and mucous membranes derived from human exposure data, the in vitro data were more than 80% predictive of the in vivo classifications. PMID- 4040073 TI - An in vitro cytotoxicity test to predict the ocular irritation potential of detergents and detergent products. AB - Two in vitro cytotoxicity procedures, the measurement of cell-membrane integrity using fluorescein diacetate and ethidium bromide, and the quantitation of the release of a cell-membrane-bound enzyme, alkaline phosphatase, were used to assess the cytotoxicity of a range of cationic, anionic and nonionic detergents. The in vitro results were compared with the in vivo irritancy of these compounds in the rabbit eye. Although in general the decreasing order of potency of cationic, anionic and nonionic detergents was similar in vivo and in vitro, there were some apparent anomalies which may be due to the differing penetration characteristics of the detergents, as indicated by electrical impedance measurements of the isolated cornea. The study was extended to an examination of the cytotoxicity of a range of completely soluble, detergent-based formulations in a suspension culture of mouse fibroblasts. In this case the in vitro results correlated more closely with those from the in vivo tests. PMID- 4040074 TI - A battery of potential alternatives to the Draize test: uridine uptake inhibition, morphological cytotoxicity, macrophage chemotaxis and exfoliative cytology. AB - Four assays that may serve as components of a battery of alternatives to the conventional Draize test were described. The exfoliative cytology assay is a refinement of the Draize test that may provide a more sensitive and more objective end-point. The macrophage migration assay addresses the inflammatory aspects of the physiological response to irritation. The uridine uptake inhibition assay uses a quantitative, reversible end-point to detect the short term action of agents on cell membranes and cell phosphorylative potential. Finally, the cytological assay serves as a rapid, easily performed general indicator of cytotoxic action. The two latter assays have been demonstrated to correlate very well with Draize test results and with each other for a wide range of test agents. PMID- 4040075 TI - Toxicity of commercial products on cells in suspension culture: a possible screen for the Draize eye irritation test. AB - Incubation of LS cells in suspension for 4 hr in the presence of water-soluble commercial products with known Draize rabbit-eye irritation potential has shown that viability, as indicated by fluorescent dyes, is a credible screen for irritation. For product formulations containing immiscible and/or insoluble substances, there are difficulties that have been reduced by extraction of the soluble components of the formulations into the culture medium. A more sensitive and automated, though more expensive, technique based on the estimation of intracellular ATP levels has been developed and the ATP50 values (concentration that reduces intracellular ATP by 50%) for several substances indicate that this may be another suitable endpoint in cytotoxicity screening for animal irritation studies. PMID- 4040076 TI - Prediction of the eye irritation potential of shampoos using the in vitro SIRC cell toxicity test. AB - Shampoos predicted to vary over a wide range in their potential to cause eye irritancy were tested in SIRC rabbit corneal cells for cytotoxicity. Six shampoos at at least ten different concentrations were added to culture dishes containing the SIRC cells and were administered at a dose of 0.01 ml directly to the corneal surface of the albino rabbit eye. When the shampoos were ranked both according to their relative toxicities in vitro and according to their relative irritancies in the modified Draize test the resulting rank orders were in perfect agreement. The results demonstrate that the SIRC cell line is a suitable model system for screening shampoos of differing surfactant compositions without the need to use live animals. Further, results obtained from the SIRC cell assay should aid in the selection of final product formulations for in vivo testing as part of the pre-market clearance process. PMID- 4040077 TI - Hen's egg chorioallantoic membrane test for irritation potential. AB - The increasingly large number of chemicals introduced onto the market and into the environment has necessitated the monitoring of environmental materials and specimen banking, as well as the development of rapid and reliable methods for the evaluation of toxicity. The Hen's Egg Test, or Huhner-Embryonen-Test (HET) is a rapid, sensitive and inexpensive toxicity test and can give information on embryotoxicity, teratogenicity, systemic and immunopathological effects, metabolic pathways and now, in developed form, on mucous-membrane irritation potencies of chemical substances. Testing with incubated hen's eggs is a borderline case between in vivo and in vitro systems and does not conflict with ethical and legal obligations especially animal protection laws. In the special field of mucous-membrane irritation testing, a specific score and classification scheme was developed for the HET, which allows risk assessments analogous to the Draize scheme. There is a good correlation between the results for HET tests on a variety of pyrithiones, phenols and isothiazolinones, and the corresponding data based on Draize tests. HET chorioallantoic membrane testing should and could not entirely replace current irritation tests in mammals, but it can diminish the number of investigations with mammals, as well as limit or eliminate pain and injury during animal experiments and allow regulators to set priority and toxicity categories. PMID- 4040078 TI - The chick embryo in toxicology: an alternative to the rabbit eye. AB - The chorioallantoic membrane (CAM) of the chick embryo is readily accessible for experimentation. It is a complete tissue that responds to injury with classical inflammatory reactions. It is limited to the late phase of embryologic life, and is without the sense of pain. Focal topical application of various household products onto the CAM results in local injury and reactions that differ in severity from one product to another. For any single product, tested as a sequence of dilutions on a series of membranes, the CAM responds with decreasing intensity that parallels the decreasing dosage. The membrane is prepared for study according to the method of Zwilling (Transplantn Bull 1959, 6, 115). The test material is applied in a Teflon ring to the 14-day-old CAM, to localize the application site. The macroscopic response is scored on day 17 of incubation. The results of analysis of histological preparations are found to correlate with macroscopic appearance. When a series of preparations was ranked according to the severity of the response each induced on the CAM, there was a good correlation with the ranking of the same preparations in the Draize test. PMID- 4040079 TI - Irritant action due to physico-chemical parameters of test solutions. AB - The irritant action of various buffer solutions was determined by the mouse skin test. All results for isosmolal solutions differing in initial pH values and buffer capacities could be satisfactorily represented by a general model which could be used to predict the irritancy of solutions with unphysiological pH values in contact with mucous membranes. The results obtained with hyperosmolal solutions are as yet too limited for such a general statement, but it appears that increasing osmolality gradually overrides the effect of the pH value. The relevance of the results to the prediction of irritant potentialities for man has been assessed by comparison with results of rabbit-eye tests carried out by Friedenwald et al. (Archs Ophthal., N.Y. 1944, 31, 279). PMID- 4040080 TI - Use of cultured human conjunctival and other cells to assess the relative toxicity of six local anaesthetics. AB - The effects of six local anaesthetics on five cell types were investigated in vitro, with the objectives of assessing their toxicity to the cell types with which they would be likely to come into contact, ranking them in order of toxicity, determining whether toxicity was related to potency, and investigating a range of indices of toxicity. Procaine, lignocaine, piperocaine, amylocaine, amethocaine and cinchocaine all showed some toxicity increasing in that order. The indices of toxicity studied all led to the same ranking order of the drugs, and this order was also the order of their anaesthetic potencies. Thus cell culture was shown to be a useful means of investigating local anaesthetics for toxicity. PMID- 4040081 TI - Ocular tolerance assessment--integrated tier policy. AB - A tier scheme is proposed for the assessment of ocular tolerance as part of the safety evaluation of materials. The scheme has four stages: (1) physico-chemical characterization, (2) an in vitro cytotoxicity study, (3) a dermal tolerance study in rabbits and (4) initial and confirmatory ocular tolerance studies in rabbits. The assessment may be terminated at any of the stages, including during the course of the final stage. This tier system appears to provide a considered and careful approach to the requirement to assess the ocular tolerance of those materials for which conventional animal tests are not essential. PMID- 4040082 TI - Distribution of eye irritation scores of industrial chemicals. AB - Eye irritation results obtained in tests on agricultural and industrial chemicals (raw materials, intermediates, formulation components and sales products) were classified on the basis of an arbitrary breakdown of the scores (which ranged from 0 (no irritation) to a maximum of 110) into six categories. This showed that of the materials (about 600) tested over a 2-year period, 18-31% caused no irritation at all, 42-51% caused minimal irritation (scores of 0.1-10.9), 9-17% were classed as slightly irritant (11.0-25.9) and 8-12% as moderately irritant (26.0-55.9), while 2-6 and 1-5% came into the categories of strong and extreme irritants, respectively (with scores of 56.0-84.0 and 84.1-110). Testing of the last two groups involves the test animals in discomfort, but because of the seriousness of eye damage to man this cannot always be avoided. PMID- 4040083 TI - The in vitro assessment of eye irritancy using isolated eyes. AB - Rabbit eyes were removed and held in temperature-regulated chambers and irrigated with saline. A dose of 0.1 ml of test irritant was applied to each eye (six eyes per test material) and the induced change in corneal thickness measured over a 5 hour period, using a Zeiss photoslit-lamp microscope. A total of sixty materials were assessed and the results graded and compared with in vivo effects. The results show that this in vitro test can be relied upon to provide a rapid, accurate prediction of the irritancy potential in vivo, with a wide range of chemicals and, as such, offers a reliable alternative to the use of live animals. PMID- 4040084 TI - Evidence from two classic irritation tests for an anti-inflammatory action of a natural extract, Echinacina B. AB - The roots of Echinacea angustifolia (fam. Compositae) were used to obtain an antiphlogistic, immunostimulating and skin repairing extract. On the basis of these potential actions, the extract is used in cosmetic preparations. The aim of this study was to evaluate the anti-inflammatory activity of the extract using different irritation tests. The irritation reaction was induced by application of 0.015 ml of 0.25% croton oil in water to the ears of mice. The raw extract (Echinacina B), topically applied, inhibited oedema both at the maximum (6 hr) and in the decreasing phase (18 hr), and this effect was directly proportional to the doses used. Echinacina B was found to be more potent than the positive control, benzidamine, a topical non-steroidal anti-inflammatory drug. In addition, the extract given iv 1 hr before injection of 0.05 ml of 1% carrageenan into the hind paws of rats inhibited oedema in the histaminic and in the later phases of the phlogistic process. These data show the qualitative value of irritation tests for studying the anti-inflammatory action of a natural plant extract. PMID- 4040085 TI - Biopharmaceutical test of ocular irritation in the mouse. AB - A simple and accurate test for ocular irritation in mice has been developed in which the subjective evaluation of intolerance is supplemented by an objective measurement, based on the change in corneal permeability following ocular damage. An episcopic microscope is used to detect, under blue light, the amount of fluorescein that diffuses across the inflamed or damaged cornea. The fluorescence emitted by this fluorochrome is quantified by a photomultiplier. The degree of ocular damage is expressed as a fluorescence index which can be subjected to statistical analysis. In a first stage of this study a series of surfactants has been examined and classified on the basis of their fluorescence index. The classification thus obtained is in agreement with those previously reported in the literature for assessment of ocular irritation by other methods. PMID- 4040086 TI - Effects of methyl linoleate hydroperoxide and hydrogen peroxide on N-nitrosation of dimethylamine. AB - The effects of methyl linoleate hydroperoxide and hydrogen peroxide on the N nitrosation of dimethylamine were investigated. Hydrogen peroxide inhibited the formation of N-nitrosodimethylamine by the reaction of dimethylamine and nitrite in citrate buffer (pH 3-5). The inhibitory effect was due to the loss of available nitrite by quantitative conversion into nitrate. The formation of N nitrosodimethylamine from the reaction of dimethylamine and nitrous acid in chloroform was effectively inhibited by methyl linoleate hydroperoxide. The inhibitory effect of the hydroperoxide was much greater than that of methyl linoleate. The loss of nitrous acid from the reaction mixture was due to the conversion of nitrous acid into nitric acid and the formation of two adducts, both of which contained nitrogen and had peroxide and carbonyl or carbonyl liberating functions. It is suggested that unsaturated fatty acids and lipid hydroperoxides are effective inhibitors of nitrosamine formation. PMID- 4040087 TI - Toxicity of Diplodia maydis in farm and laboratory animals. AB - The acute toxicity of maize culture material of eight strains of Diplodia maydis in ducklings, as well as the ability of five of these strains to induce typical diplodiosis (a neuromuscular disease) in cattle and sheep was shown. Typical diplodiosis was induced in 17 sheep and 11 cattle. Two of the five toxic strains were isolated from maize involved in diploidiosis outbreaks, the others from commercial maize. Strains inducing diplodiosis could be isolated from commercial maize from the USA, Argentina and South Africa. There was no correlation between the toxicity of D. maydis strains in ducklings and their ability to induce diplodiosis in cattle and sheep. Some isolates were acutely toxic to ducklings and rats but were unable to induce diplodiosis in either cattle or sheep. Others, equally toxic to ducklings and rats, induced diplodiosis in cattle and sheep at low dose levels. Two doses, each of 5 g/kg, of maize culture material of isolates from the USA, Argentina and South Africa induced diplodiosis in sheep. Culture material incubated for less than 8 wk could not induce diplodiosis in cattle. Acute toxicity in ducklings and rats also increased with longer incubation periods. Cultures of non-sporulating and profusely sporulating strains were equally toxic to ducklings. Heat treatment of culture material for 48 days at 45 degrees C failed to reduce toxicity in ducklings. PMID- 4040088 TI - Hydrocarbon hydroxylation system in liver microsomes from four animal species. AB - The in vitro metabolism of n-heptadecane was investigated using hepatic microsomes from Hubbard chickens, New Zealand rabbits, Wistar rats and rainbow trout. Incubations with the 14C-labelled alkane for 1 hr showed that the rate of oxidation varied between species; the rate (per mg protein) in chickens was roughly 20-fold greater than the rate in trout, and roughly 10-fold greater than the rates in rats and rabbits. On the basis of cytochrome P-450 content, the rate of heptadecane metabolism was roughly 20-fold greater in the chicken than in the other species. Moreover, the lambda max Soret band of the reduced cytochrome P 450 CO-complex was observed at 452 nm in the chicken. Correlation between the rate of heptadecane metabolism and in vivo storage levels is discussed. PMID- 4040089 TI - Do particles translocate from the vagina to the oviducts and beyond? AB - To investigate whether particles deposited in the vagina translocate to the oviducts, 0.3 ml of a 4% bone black suspension was deposited in the posterior vaginal fornix of each of five cynomolgus monkeys (Macaca fascicularis) during their mid-menstrual cycle. Simultaneously, each animal received 10 units of oxytocin by intramuscular injection. The oviducts of three animals were removed 1 hr after administration of the bone black, while those of the remaining two animals were removed 72 hr after dosing. The removed oviducts were flushed with Hank's solution and then with collagenase solution. The solutions were collected in clean vials and filtered. The filters were examined for bone black particles by light microscopy, as were filters through which solution blanks (negative controls) had been passed. Particles resembling bone black were found on all filters. There were no appreciable differences in the number or shape of these particles between the solution-blank filters and the oviduct-flush filters. The particles on both the solution-blank filters and on the oviduct-flush filters probably originated from environmental contamination by ubiquitous carbon particles. While these results suggested that no translocation took place, translocation could not be ruled out with certainty in the absence of quantitative analyses. A more definitive pilot study was then conducted with two dosed monkeys and one control, using talc labelled by neutron activation to circumvent the problem of environmental contamination. Gamma-Ray analysis of tissue and peritoneal lavage samples for the radionuclides 46Sc, 59Fe and 60Co indicated that no measurable quantities (i.e. greater than 0.5 micrograms) of talc translocated from the deposition site in the vagina to the uterine cavity and beyond. PMID- 4040090 TI - Identification and assessment of the effects of chemicals on reproduction and development (reproductive toxicology). AB - Most studies for determining the reproductive toxicity of a chemical have to be conducted with whole animals. Test procedures used to investigate parts or the whole of the reproductive cycle are described in current guidelines. Other techniques, such as in vitro methods, and those for investigating specific events in the cycle, are under development. Epidemiological studies can give valuable information, although they are difficult to perform and interpret in practice. There is a need for more epidemiological studies of exposed populations and for recording and quantifying the concentrations of chemicals to which such populations are exposed. It is suggested that animal experiments should be programmed in a stepwise manner, and should take into account effects seen in previous toxicity studies. The programme of tests for determining reproductive toxic potential should be established on a case-by-case basis, since many factors will influence the choice of studies and the sequence in which they should be performed. PMID- 4040091 TI - It's coffee time again! PMID- 4040092 TI - Saccharin: current status. PMID- 4040093 TI - Characterization of aminosaccharins in commercial sodium saccharin produced by the Maumee process. AB - The most abundant polar impurities detected by ion-pair high-pressure liquid chromatography of sodium saccharin produced by the Maumee process were identified as 5- and 6-aminosaccharin. The combined levels of these compounds in the samples analysed ranged from 99 to 152 mg/kg. Other less abundant polar impurities identified in Maumee process sodium saccharin were 7-aminosaccharin and o sulphamoylbenzoic acid. Mutagenicity assays of 5-aminosaccharin, 6-aminosaccharin and a polar impurity fraction isolated from Maumee saccharin, gave negative results. PMID- 4040094 TI - Some changes in gastro-intestinal metabolism and in the urine and bladders of rats in response to sodium saccharin ingestion. AB - In rats fed sodium saccharin in the diet changes in urine composition, increased bladder-tissue mass and, in males only, an accumulation of minerals in the bladder tissue have been observed. In this report evidence is presented that indicates that these changes are a consequence of the effects of sodium saccharin in the gastro-intestinal tract and are not due to systemic sodium saccharin. Sodium saccharin has been shown to inhibit gastro-intestinal enzymes that digest carbohydrates and proteins and to increase caecal absorption of mineral ions. The significance of these findings to saccharin-associated bladder tumorigenesis is discussed. PMID- 4040095 TI - The effects of high dietary levels of sodium saccharin on mineral and water balance and related parameters in rats. AB - The effects of sodium saccharin (NaS) treatment on mineral and water balance and a number of related parameters were studied over a 10-day period in 7-month-old Charles River CD rats. Eight groups of 10 male and 10 female rats were studied. In four of the groups the rats were the F1 offspring of rats that had been exposed to NaS at 1, 3, 5 or 7.5% in the diet and the offspring were treated with the same dietary levels of NaS as their parents. Prior treatment in two other groups was modified in order to evaluate the role of in utero exposure to NaS on the study parameters: rats in one group were only exposed in utero via dams fed diets containing 5% NaS while treatment in the other group did not include in utero exposure, but was started at birth via dams fed diets containing NaS and continued at a dietary concentration of 5% NaS. Second-generation rats in another group were fed diets containing 5% sodium hippurate (NaH), a compound with a number of physical and chemical properties similar to those of NaS; this group was included in order to evaluate the specificity of NaS and/or the effect of sodium on the study parameters. A group of untreated rats served as controls. Treatment-related effects were observed in most study parameters. In addition, a number of differences between male and female rats in baseline values and/or in response to NaS administration were observed. With increasing dietary levels of NaS body weights decreased, but there were increases in water consumption, faecal water content, and caecal weights. NaS treatment resulted in increased urine volume and decreased urine osmolality, changes in urine mineral concentrations (increased sodium, decreased potassium and zinc) and increases in fresh and dry bladder weights, bladder-tissue hydration, and mineral concentrations (sodium, potassium, magnesium and zinc) in bladder tissue. The parameters in which clear sex-related differences in baseline values were observed were body weight, food and water consumption, urine volume, urine osmolality, fresh bladder mass, bladder-tissue hydration and the concentrations of sodium, potassium, magnesium and zinc in the bladder tissue. With the exception of urine osmolality, the values were higher in females. Differences between males and females in response to treatment were observed for NaS consumption (increased in females), caecal weight (increased in females), NaS concentration in the urine (increased in males), and the concentration of sodium, potassium, magnesium and zinc in the bladder tissue (increased in males).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 4040096 TI - Evaluation of the dose response and in utero exposure to saccharin in the rat. AB - A two-generation bioassay on sodium saccharin (NaS), involving 2500 second generation male rats, was designed to determine the dose response for urinary bladder tumours in male rats and to evaluate other changes possibly related to the occurrence of the tumours. Six treatment groups (125-700 rats/group) were fed dietary levels of NaS ranging from 1.0 to 7.5%. To evaluate the role of in utero exposure, two additional groups were exposed to NaS either only during gestation via dams fed diet containing 5.0% NaS or for a single generation beginning at birth. In the latter group, the nursing dams were placed on an NaS diet immediately after giving birth and their offspring were weaned onto diets containing 5.0% NaS. A third additional group, included to evaluate the specificity of NaS and the role of excess sodium in the occurrence of urinary bladder tumours, was fed diet containing sodium hippurate (NaH) for two generations--5.0% NaH to the first generation and to the second until 8 wk old, and subsequently 3.0% because of unexpected toxicity. A clear dose response for urinary bladder tumours was observed in the second-generation NaS-treated male rats. The steep slope of the dose-response curve indicated a rapid decline in tumour incidence with decreasing dose. The 1.0% dietary level (fed to 700 rats) was considered to be a no-effect level for bladder tumours. The only other treatment-related pathological changes were an increase in urinary bladder weight in rats fed greater than or equal to 3.0% and an increase in mineralization of the kidneys with greater than or equal to 1.0%. Several physiological effects were seen in the NaS-treated groups showing an increase in bladder tumours (i.e. those fed greater than or equal to 3.0%). Some changes, e.g. depressed growth and increased water consumption, were indicative of a general disturbance of these rats, but analysis of body-weight, food-consumption, compound-consumption and water-consumption data revealed no correlations within any dose group between these quantitative data and the occurrence of bladder tumours. Other changes indicative of the compromised situations of the rats fed high dietary levels of NaS were anaemia in weanling rats fed 5.0 or 7.5% and a reduction in litter size at dietary levels greater than or equal to 3.0%. Changes in urine volume and urine osmolality were highly correlated with the occurrence of the urinary bladder tumours.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 4040097 TI - Histopathological evaluation of rat urinary bladders from the IRDC two-generation bioassay of sodium saccharin. AB - Bladder tissues from rats treated with sodium saccharin in a two-generation dose response study, in which 1.0% in the diet had been identified as the no-effect level for primary bladder cancer, were re-examined without knowledge of the test groups or the previous histopathological findings. Compound-related increases in the incidences of hyperplasia were found at the 6.25 and 7.5% saccharin levels (the highest dietary levels tested). There were also compound-related increased in the incidence of transitional-cell papillomas and/or carcinomas at the 4.0, 5.0, 6.25 and 7.5% levels. There was a slight increase in the incidence of transitional-cell carcinomas at the 3.0% level, but this was not statistically significant (P = 0.25). No compound-related effects were evident at the 1.0% level. All tumours were well to moderately differentiated and there was no increase in mean grades of severity or anaplasia for any proliferative lesion. PMID- 4040098 TI - A cancer risk assessment for saccharin. AB - The results from a recently completed large experiment with rats exposed to saccharin show that the dose-response function is much steeper than was previously assumed. Based on this observed steepness, any implied cancer risk at the low doses of interest to man is very small. PMID- 4040099 TI - Multi-stage carcinogenesis in the urinary bladder. AB - Sodium saccharin has been shown to be a promoting substance for urinary bladder carcinogenesis in the rat following initiation with N-methyl-N-nitrosourea, N-[4 (5-nitro-2-furyl)-2-thiazolyl]formamide (FANFT), or N-butyl-N-(4 hydroxybutyl)nitrosamine. It has been shown to have many of the properties of promoting substances in other animal models, such as the mouse skin; it lacks mutagenic activity, induces hyperplasia in the target tissue, and does not bind DNA. It has recently been demonstrated to be co-carcinogenic for the rat bladder. It has also been shown that the administration of sodium saccharin during the regenerative hyperplasia observed after freeze ulceration or cyclophosphamide administration resulted in the induction of bladder tumours, even without pre initiation with FANFT or other known initiating substances. This model appears to be analogous to the administration of sodium saccharin to animals with a rapidly proliferating bladder mucosa as occurs in utero during the two-generation carcinogenesis experiments and in the pellet-insertion experiments in which a cholesterol pellet containing sodium saccharin is inserted into the bladder. To enhance our understanding of the complex interaction of the many variables involved in two-stage bladder carcinogenesis, a stochastic model has been formulated based on long-term carcinogenicity and in vivo tissue kinetic studies. This model indicates the importance of cell proliferation and the development of hyperplasia in carcinogenesis. PMID- 4040100 TI - Saccharin--current status. Report of an expert panel. Scientific review group. PMID- 4040101 TI - Chronic toxicity/carcinogenicity study of FD & C Blue No. 2 in rats. AB - FD & C Blue No. 2 was fed to rats in the diet in a long-term toxicity/carcinogenicity study. The study included an in utero phase in which the compound was administered to groups of 60 male and 60 female Charles River CD albino rats at levels of 0.5, 1.0 and 2.0%. Two concurrent control groups, each containing 60 rats of each sex, received the basal diet. After random selection of the F1 animals, the long-term phase was initiated at the same dietary levels, with 70 rats of each sex in each dose group and in each of two control groups. Maximum exposure was 30 months. No consistent compound-related biologically adverse effects were noted. There were random statistically significant differences from the controls with respect to body weight, food consumption and clinical chemistry tests. Food consumption by the test groups showed a dose related increase. This was probably due to the non-nutritive character of the colouring. A statistically significant increase in gliomas in the high-dose male rats was not found to be biologically significant, since none of the criteria for determining the neurocarcinogenic potential of chemical substances was met. The overall brain-tumour incidence in this study was within the range typical for 2 yr-old CD rats. Under the conditions of this study, FD & C Blue No. 2 did not produce evidence of any toxicity, including carcinogenicity. PMID- 4040102 TI - Influence of dose and sex on the disposition and hepatic effects of cinnamyl anthranilate in the B6C3F1 mouse. AB - Cinnamyl anthranilate is a synthetic food flavouring and fragrance agent, formerly used at very low levels. There is currently some concern over the potential risk to man from its use, since it has been found to cause liver tumours in mice, following the administration of very large doses. This paper reports studies of its disposition and hepatic effects in B6C3F1 mice in relation to dose. Following a single oral dose of 500 mg cinnamyl anthranilate/kg body weight to B6C3F1 mice peak plasma levels of unchanged compound were reached in 30 min, and were higher in males than in females. Unchanged cinnamyl anthranilate in the urine accounted for 0.3-0.4% of the dose. Anthranilic acid (c. 17%) and hippuric acid (35%; the major metabolite of cinnamyl alcohol) were present in the urine, and recoveries of both were higher in females. Groups of male and female B6C3F1 mice were given 0, 10, 100, 1000, 5000, 15,000 and 30,000 ppm cinnamyl anthranilate in the diet. After 4 days, the diet was removed and urine collected for 24 hr. This contained cinnamyl anthranilate (more in males) hippuric and anthranilic acids (more in females) in concentrations that increased with dose. Other animals were given these diets for 19 days and then killed. Relative liver weight and hepatic microsomal cytochrome P-450 increased with increasing dose above 1000 ppm cinnamyl anthranilate, more markedly in males than in females although the maximum response (roughly twofold) was very similar in the two sexes. SDS-PAGE examination of the microsomes revealed the induction of a cytochrome P-450 isozyme of 53.1 kDa, but the aniline hydroxylase and p nitroanisole O-demethylase activities of the 9000 g supernatant of liver were not induced. The data are discussed in terms of their significance for the human safety evaluation of cinnamyl anthranilate. It is important to note that liver hypertrophy, microsomal enzyme induction and the excretion of unchanged cinnamyl anthranilate all have the same dose-threshold for their appearance. This suggests that the hepatic effects of cinnamyl anthranilate may be mediated by unhydrolysed cinnamyl anthranilate, which is present only at very high doses due to the saturation of its hydrolysis. PMID- 4040103 TI - Tumorigenicity study of butyl and isobutyl p-hydroxybenzoates administered orally to mice. AB - Butyl p-hydroxybenzoate (n-BHB) and isobutyl p-hydroxybenzoate (i-BHB) were administered orally to ICR/Jcl mice at concentrations of 0.6 (maximum tolerated dose), 0.3 or 0.15% in the diet for up to 102 wk. Tumours were observed at various sites including the haematopoietic system, the lung and the soft tissue. However, at none of the sites did the tumour incidence or the time to death with tumours differ significantly from that in the untreated control group. PMID- 4040104 TI - Thermal conversion of trimethylamine-N-oxide to trimethylamine and dimethylamine in squids. AB - The levels of dimethylamine-nitrogen (DMA-N), trimethylamine-nitrogen (TMA-N) and trimethylamine-N-oxide-nitrogen (TMAO-N) were determined in five species of dried squid. Each sample contained extremely high levels of TMAO-N (2558-8064 ppm) and moderate amounts of TMA-N (121-503 ppm) and DMA-N (124-373 ppm). Over 90% of TMAO N in squid was converted to TMA-N and DMA-N after heating at 200 degrees C for 1 hr; approximately 50% of the volatile TMA-N and DMA-N was lost during the course of the heating. The thermal conversions were accelerated by heat, and possibly involved catalysis by certain tissue constituents. Squids are a popular seafood in most oriental countries, but before appearing on the market they are subjected to a long food-processing procedure. Therefore, a high concentration of TMAO in squids is an important problem, for food technology as well as toxicology. PMID- 4040105 TI - Genotoxicity testing of cigarette-smoke condensate in the SCE and HGPRT assays with V79 Chinese hamster cells. AB - The genotoxicity of cigarette-smoke condensate (CSC) was investigated using V79 Chinese hamster fibroblasts in the sister-chromatid exchange (SCE) and HGPRT (hypoxanthine-guanine-phosphoribosyl-transferase) tests. CSC was negative in the SCE test both with and without metabolic activation (co-cultivation with chick embryo primary hepatocytes). In the HGPRT test no direct mutagenicity of CSC was observed but after metabolic activation there was a considerable increase in the number of mutants. Comparison of different metabolizing systems showed that non induced chick hepatocytes, liver homogenate from non-induced chick embryos and liver homogenate from rats pretreated with Aroclor 1254 generated similar numbers of mutants in cells treated with CSC. In addition the capacity of CSC to inhibit metabolic co-operation between V79 cells was studied. A dose-related increase in the inhibition of metabolic co-operation was observed. PMID- 4040106 TI - Maternal-foetal distribution studies in late pregnancy. I. Distribution of [N methyl-14C]betaine in tissues of beagle dogs and miniature pigs. AB - [N-Me-14C]Betaine was administered iv as a single dose (5 mg/kg) to pregnant beagle dogs and miniature pigs late in gestation. Two hr after administration of the radiolabel, when the compound was in equilibrium, the dams were killed and the foetuses were removed for determination of the radioactivity in maternal and foetal tissues. Eight litters of dogs (56 foetuses) and four litters of pigs (30 foetuses) were examined. The distribution of betaine in both species showed distinct differences between maternal and foetal tissues, indicating definite placental barriers; the placental distribution factor was estimated to be 52.3% in dogs and 97.8% in pigs. The blood/brain distribution factor was 84.6% in maternal dogs, 89% in maternal pigs, 65.7% in foetal dogs and 0% in foetal pigs. In the dog, maternal liver was the largest depot of the administered betaine, followed by foetal liver. Foetal heart, lung and kidney tissues also incorporated radiolabelled betaine. The highest concentrations of betaine in the pig were found in maternal kidney and liver. PMID- 4040107 TI - Studies on the design of animal tests for the corrosiveness of industrial chemicals. AB - Using a defined method for the determination of irritant and corrosive effects, the effects of varying the exposure time and the extent of occlusion were investigated and compared in rabbit skin experiments (by occlusive and semi occlusive methods, each at exposure times of 1 hr and 4 hr). The results for 23 substances demonstrate that exposure for 1 hr normally leads to a realistic assessment of corrosiveness, in agreement with those given in the EEC 'Dangerous Substances Directive' (67/548/EEC; Off. J. Europ. Commun. 1967, 196, 1). With several substances, the 4-hr exposure leads to corrosive effects that do not occur under practical conditions. Moreover, a 4-hr exposure does not lead to a realistic hazard assessment in every case; some substances exhibit a corrosive effect in this test but are not classified as "corrosive" in the EEC Guideline Annex I, no. 1.1. Results using the semi-occlusive method did not usually differ from those obtained with the occlusive method. In general, the semi-occlusive method can be used, and in the case of volatile substances it is strongly advocated. PMID- 4040108 TI - Carcinogenicity study of a commercial sodium oleate in Fischer rats. AB - Sodium oleate was added to the drinking-water of groups of 50 male and 50 female F344 rats at levels of 2.5 and 5.0% for 108 wk. The mean liver weight in males given 5% oleate was lower than that of the males given 2.5% oleate or distilled water alone. The mean thymus weight of females given 5% oleate was higher than that of females given 2.5% oleate or distilled water. There were no statistically significant differences between treated and control rats in the results of the urine and serum analyses or haematological determinations or in the incidence of tumours, apart from pancreatic tumours. The latter, in the males, showed some increase over the concurrent controls but did not differ significantly from the reported spontaneous incidence in this strain. It was concluded that sodium oleate does not induce tumours when given orally to F344 rats. PMID- 4040109 TI - Chromosomal studies in diabetic patients treated with chlorpropamide. AB - Chromosome studies were carried out on the peripheral blood of nine diabetic patients treated with chlorpropamide, on nine healthy controls and on nine untreated diabetic controls. Data from each treated individual were compared with the mean of the pooled data from the two control groups. There was a statistically significant increase in the individual numbers of sister chromatid exchanges per metaphase in each of the patients treated with the drug compared with the mean of the pooled control values. There was no significant increase in the numbers of structural chromosomal aberrations in the treated patients compared with the controls. PMID- 4040110 TI - [Development of a magnetic urethral closure device. A new procedure for the treatment of female urinary incontinence]. PMID- 4040111 TI - Influence of starvation/refeeding transition on lipogenesis and NADPH producing systems in adipose tissue, mammary gland and liver at mid-lactation. AB - Glucose-6-phosphate dehydrogenase, 6-phosphogluconate dehydrogenase and malic enzyme are enzymes involved in NADPH synthesis. Their specific activities and glucose utilization by isolated cell systems have been measured in adipose tissue and mammary gland from mid-lactating rats during starvation/refeeding transition. Starvation for 24 h produced a 75-90% decrease in the specific activities of these NADPH producing systems in mammary gland. Acinis isolated from the gland of starved rats had a lower production of CO2, fatty acids and triacylglycerols from (1-14C)glucose and (6-14C)-glucose than did gland from control rats. The activities of these enzymes in adipose tissue were very low and did not undergo any measurable alteration with starvation. The ability of adipocytes from well fed lactating rats to synthesize fatty acids from (1-14C)glucose was completely blocked. However, starvation is accompanied by a marked decrease in glucose incorporation into triacylglycerols. All the variations observed "in vivo" and "in vitro" in mammary gland returned almost to normal values by refeeding the starved lactating rats. PMID- 4040113 TI - Daily variations of plasma sex hormone-binding globulin binding capacity, testosterone and luteinizing hormone concentrations in healthy rested adult males. AB - In this study the daily variations of plasma sex hormone-binding globulin (SHBG) binding capacity were measured together with plasma testosterone and luteinizing hormone (LH) concentrations in 7 healthy rested adult males. Plasma SHBG-binding capacity demonstrated a significant circadian rhythm (acrophase = 2.06 p.m.; mesor = 0.35 +/- 0.6 ng testosterone bound/100 ml; amplitude = 17% of the mesor). Plasma testosterone also showed a circadian rhythm (acrophase = 7.02 a.m.; mesor = 4.38 +/- 0.67 ng/ml; amplitude = 18% of the mesor). The free testosterone index (or the ratio between plasma testosterone and SHBG-binding capacity) was not correlated with plasma LH levels. In our hands this last parameter did not vary according to a circadian pattern. These data are discussed in terms of a feedback mechanism controlling the pituitary-testis axis regulation. PMID- 4040112 TI - The time sequence of adaptive changes to dietary phosphorus deficiency in the chick. AB - Ten-day old chicks were divided into 6 groups which were fed a low phosphorus (P) diet for periods of 0, 0.5, 1, 3, 7 or 11 days before killing at 3 weeks old. Labelled calcium (47Ca) was injected intraperitoneally into some birds 18 hours before killing. A marked fall in growth rate, plasma phosphorus level, plasma growth hormone level and renal 24-hydroxylase activity levels had occurred by 12 hours after the experimental diet had started. After one day on the diet, the rate of duodenal Ca absorption had risen and continued to rise up to the 11th day. During this period, the renal 25-hydroxyvitamin D-1-hydroxylase activity rose slightly while the 24-hydroxylase activity rose towards the control level. At 24 hours, the 47Ca level in the bone was markedly lower than in the control group and remained low. It was concluded that the first adaptive response of the chick to dietary P insufficiency was to suppress growth. Subsequent adaptive responses were to increase the rate of Ca and P absorption from the gut and mobilisation from the bone but despite these measures, the growth rate only recovered slightly and the plasma P level continued to fall. PMID- 4040114 TI - Serum testosterone, male dominance, and aggression in captive groups of vervet monkeys (Cercopithecus aethiops sabaeus). AB - The relationship of serum testosterone concentration to male dominance rank and frequency of aggression was investigated in stable vervet monkey social groups, each containing two or three adult males, several adult females, and their offspring. Dominance relationships were determined by noting an animal's success in intermale aggressive encounters. A striking finding was the marked within subject variation in testosterone concentration: 5- to 10-fold fluctuations were often observed on successive days. When all 15 groups were considered together, testosterone concentration was unrelated to dominance rank. Although mean testosterone concentration for all dominant males was higher than the mean for all subordinate males, this difference was not significant. In a subset of 4 groups, the rate of aggression initiated was significantly correlated with same day testosterone in dominant but not in subordinate males. PMID- 4040115 TI - Short-term changes in plasma levels of hormones during establishment and defense of a breeding territory in male song sparrows, Melospiza melodia. AB - When territorial male song sparrows are captured and removed from their territories, previously unmated and nonterritorial males will take over those vacant territories within 12-72 hr. Plasma levels of testosterone are elevated in these replacement males as well as in their neighbors. Since the latter already have territories, it is suggested that the agonistic interactions over territory boundaries, or behavioral stimuli from challenging males, rather than ownership of a territory per se, stimulates secretion of testosterone. To test this hypothesis further, male song sparrows were challenged by experimental simulation of a territorial intrusion. This procedure involved placing a caged male song sparrow in the center of the subject's territory and playing tape recorded conspecific song through an adjacent speaker. Responding males were then captured at intervals after onset of the intrusion. Plasma levels of testosterone were significantly higher in males exposed to experimental territorial intrusion than they were in controls, supporting the hypothesis that behavioral stimuli emanating from an intruding male can act as supplementary information stimulating secretion of testosterone. PMID- 4040116 TI - Harderian letdown in male mongolian gerbils (Meriones unguiculatus) contributes to proceptive behavior. AB - Adult female gerbils in estrus, like other female rodents, tend to engage in proceptive displays toward conspecific males. The displays, which may be interspersed with the more usual female agonistic activity, if the males are strangers, are preceded by female olfactory investigation of those head areas in the male gerbil where Harderian letdown accumulates most densely. This study explored the possibility that the male Harderian glands are a source of olfactory signals which promote proceptive behavior but suppress female agonistic behavior. Female gerbils in estrus were found to display significantly less than normal rates of proceptive behavior toward Harderianectomized males. The proceptive activity which was observed appeared to be slowed, but the typical pattern was retained. Female aggression, however, was not affected by their estrous condition or by the Harderian state of the males. Possibly Harderian letdown in male gerbils may inform females as to the reproductive competence of the males. PMID- 4040117 TI - Dazoxiben, a prototype inhibitor of thromboxane synthesis, has little toxicity in laboratory animals. AB - Dazoxiben, an orally active specific inhibitor of thromboxane synthetase, was administered by mouth daily to dogs and rats for 6 months. Dogs showed no evidence of toxicity up to 300 mg day-1 kg-1, the highest dose level used. Rats showed no evidence of toxicity after 100 mg day-1 kg-1, but at 300 mg day-1 kg-1 there were slight increases in plasma calcium and urea concentrations and a moderate incidence of focal nephrosis; males showed a slightly increased platelet count. Studies in rats and rabbits at dose levels up to 400 mg day-1 kg-1, by mouth, revealed no adverse effects on male or female fertility, embryogenesis, parturition or postnatal development. As dazoxiben is well absorbed after oral administration, the generally negative outcome to these toxicity studies suggests that selective inhibitors of thromboxane synthesis may be largely free of adverse effects which might impede their therapeutic or prophylactic use in clinical medicine. PMID- 4040118 TI - Two-dimensional echocardiographic features of right ventricular anomalous muscle bundle. PMID- 4040119 TI - Life-phase specific induction and expression of rapid expulsion in rats suckling Trichinella spiralis-infected dams. AB - Rat dams infected with 1000 Trichinella spiralis muscle larvae, 4 weeks prior to breeding, provided their suckling offspring with immunity to challenge with 200 muscle larvae at 2 weeks of age. The immunity was expressed in the elimination of 75-99% of the challenge dose within 24 hr. The intestinal worm burden did not decline significantly after the initial expulsion. Infected dams continued to protect their offspring during three breeding cycles, for as long as 26 weeks after infection. Immunity was conferred upon pups by dams that had been selectively immunized with the parenteral phase of the parasite's life cycle. Immunization with a drug-terminated enteral infection was ineffective as was enteral immunization followed by the parenteral phase. Further analysis revealed that rapid expulsion by pups was dependent on the number of mature muscle larvae recovered from dams immunized with NBL. By comparison, the expulsive capacity of the same dams was not improved by increasing the numbers of NBL within the range tested. PMID- 4040120 TI - Increases in the numbers of immunoglobulin-secreting cells in lymph nodes responding to sperm and other stimuli: possible relationship to immunosuppression. AB - It has been reported that, in early pregnancy in mice, there is an increase in the number of immunoglobulin-secreting cells in the lymph nodes which drain the uterus. This paper describes the results of further investigations provoked by interest in these early changes. Increases in the numbers of immunoglobulin secreting cells were observed in syngeneically, but scarcely or not at all in allogeneically, mated mice. Increases were not observed in surgically sterilized female mice inseminated by normal males. However, subcutaneous injection of sperm provoked massive increases in the numbers of immunoglobulin-secreting cells in the lymph nodes draining the injection site. The changes were compared with those provoked by the injection of spleen cells and LPS. The results are discussed in relation to the nature of the interactions provoking the increases in the number of immunoglobulin-secreting cells and their possible relationship to immunosuppression, and the relative immunological unresponsiveness which the female shows to the challenge of inseminated sperm. PMID- 4040121 TI - Lung localization of antibody-forming cells stimulated in distant peripheral lymph nodes. AB - Previous studies have shown that antibody-forming cells (AFC) produced in the lung-associated lymph nodes after lung immunization enter the blood and are subsequently extravasated into immunized lung lobes. This study evaluated AFC in blood and lung lavage fluids following simultaneous stimulation of the thoracic and popliteal lymph nodes with two antigenically distinct immunogens. Five dogs were immunized in the hind feet with rabbit red blood cells (RRBC) and in the left cardiac lung lobe with sheep red blood cells (SRBC). The number of anti-SRBC and anti-RRBC AFC in the blood and lavage fluids was periodically evaluated. The results indicated that both immunizations significantly increased the number of AFC in the blood. The number of AFC to RRBC and SRBC antigens was significantly higher in the immunized lung lobes than in the control lung lobes. A comparison of the number of RRBC and SRBC AFC in the immunized or control lung lobes, relative to the number of RRBC and SRBC AFC in the blood, indicated that AFC to both antigens entered the lung at the same rate. We conclude that AFC produced in distant lymphoid tissues enter the lung from the blood as readily as AFC produced after lung immunization. PMID- 4040122 TI - Inhibition of cells producing antigen-dependent non-specific immunoglobulins by isologous anti-erythrocyte immunoglobulins. AB - Mice injected with isologous cellulose-conjugated immunoglobulins containing antibodies to sheep red blood cells develop a specific unresponsiveness to the homologous antigen. It was shown that such animals demonstrate a sharp decrease not only in the number of antibody-forming cells but also in the number of cells secreting antigen-dependent non-specific immunoglobulins. The suppression of both processes is antigen-specific. It is suggested that the reduced appearance of cells forming antigen-dependent non-specific immunoglobulins is due to suppression either of hypothetic inductors or precursors of these cells, which resemble the precursors of antibody producers in their idiotypes. The presence of the common precursors of antibody- and antigen-dependent non-specific immunoglobulin-forming cells is an alternative possibility. PMID- 4040123 TI - Chronic ethanol consumption, stress, and hypertension. AB - A reliable method of producing physical stress in the rat was developed using heat irradiation, and the possible interaction between chronic ethanol consumption and stress was investigated in a rat model of alcoholism. Chronic heat stress and chronic ethanol consumption each produced mild hypertension in rats. When combined, the two treatments resulted in hypertension more severe than that produced by either stress or ethanol consumption alone. The group of animals receiving both treatments also exhibited high mortality. Investigations into the mechanisms responsible for the apparent additive effects of the two treatments revealed that the animals in this group had the highest circulating norepinephrine levels. The plasma volumes, however, were not different between the stressed groups and their unstressed counterparts. As the plasma norepinephrine level usually reflects overall sympathetic tone of an animal, our results suggest that the additional hypertensive effect of chronic stress on the ethanol-treated animals is associated with increased sympathetic nervous activity and is not a result of expanded plasma volume. These findings may have clinical implications for human alcoholics and in the analysis of cardiovascular risk factors in hypertensive patients. PMID- 4040124 TI - Immunoglobulin-containing cells in normal human labial salivary glands. AB - The distribution of immunoglobulin-containing cells within 8 normal human labial salivary glands was studied using an immunoperoxidase technique. Cell counts revealed that IgA-containing cells pre-dominated in all specimens and that the mean percentage class ratios for IgG:IgA:IgM:IgD cells were 4:92:3:1. IgE cells were rare and only detected in one gland. The density of IgA cells (191 cells/mm2 of labial gland section) was greater than those previously reported for the parotid and submandibular glands. These results support the view that minor salivary glands play an important role in the synthesis and secretion of salivary antibody. PMID- 4040125 TI - In vitro cisplatin effects on phagocyte functions. AB - The effects of cis-diamminedichloroplatinum (II) (cisplatin), a drug used in cancer chemotherapy, on the oxidative metabolism, endocytosis, chemotaxis and exocytosis of guinea-pig polymorphonuclear leukocytes were studied. All these functions were negatively influenced, but the same effect (50% inhibition) was observed at different drug concentrations (3 X 10(-5) M for chemotaxis, 10(-4) M for O2 consumption by FMLP and beta-glucuronidase release, 10(-3) M for O2 consumption by PMA and for zymosan engulfment). The effects of the drug can be explained by its ability to bind to membrane proteins, essentially to -SH groups. PMID- 4040126 TI - The progressive nature of subaortic stenosis in congenital heart disease. AB - Data derived from serial hemodynamic and angiocardiographic investigations on pediatric patients not subjected to intervening intracardiac operations support the view that subaortic stenosis in congenital heart disease tends to be a progressive disorder. Our data are obtained from two groups of patients. The first comprised 22 patients with discrete subaortic stenosis in relative isolation. The second was made up of 19 patients with the fibrous or fibromuscular forms of discrete subaortic stenosis associated with a perimembranous ventricular septal defect. The results from both groups support our initial contention. The progressive character of subaortic stenosis in these two situations illustrates the dynamic nature of congenital heart disease, and the tendency of a changing form and function. PMID- 4040127 TI - Horn's operation in the treatment of stress incontinence. PMID- 4040128 TI - [Light and electron microscopy of pseudoxanthoma elasticum]. AB - Five patients with recessive pseudoxanthoma elasticum (PXE-R) and four with dominant transmission of the disease (PXE-D) belonging to the same family were studied by light and electron microscopy. In PXE-R, calcification in the elastic fibres causes their enlargement, excavation and fragmentation. On the other hand, in PXE-D irregularly shaped and unevenly lined elastic strands may form an anastomotic wickerwork intimately intermingled with the collagenous texture. In other places, elastic bundles seem to be composed of very tiny elements. Both aspects represent a dysplasia of the elastic tissue. Independently of the mode of inheritance, a variable proportion of enlarged collagen fibrils exhibit a "flower like" structure. Additionally, in PXE-D alone a peculiar aggregation of small and large collagen fibrils is observed. Granulofilamentous material mixed with tiny collagen fibrils is found in both groups of patients. On the basis of our observations, PXE-R and PXE-D may be identified by light and electron microscopy. PMID- 4040129 TI - [Mycotic mycetoma (eumycetoma) caused by Madurella mycetomi]. AB - Mycotic mycetoma is a chronic, granulomatous and fistulous tropical disease caused by hyphomycetes of different families. A case caused by Madurella mycetomi is presented and the diagnostic and therapeutic possibilities discussed. PMID- 4040130 TI - Response of starter pigs to supplementation of corn-soybean meal diets with organic acids. AB - Four growth experiments were conducted to assess the effects of organic acid supplementation on performance of starter and finisher pigs. Three 4-wk starter experiments utilized 392 pigs fed simple corn-soybean meal diets. A fourth experiment employed 135 finisher pigs in a 6-wk study. Each of the starter experiments was initiated immediately after weaning; piglets were 30 +/- 3 d of age. In Exp. 1, weanling pigs fed a 19% crude protein, simple corn-soybean meal diet were compared with pigs fed similar diets supplemented with 2% propionic, fumaric, or citric acid. Addition of each acid improved (P less than .07) efficiency of gain, while propionate depressed (P less than .05) feed intake. Additions of 1, 2, 3 or 4% fumarate were made in Exp. 2, resulting in linear daily gain and feed efficiency improvements (P less than .05). In Exp. 3, a possible protein-sparing effect of fumaric acid was investigated. Increasing protein levels from 16 to 20% improved daily gain (P less than .01) and feed efficiency (P less than .0001); fumarate supplementation (2%) increased (P less than .01) gain:feed. However, there was no protein X fumaric acid interaction. In Exp. 4, no treatment effects were noted with performance of finisher pigs fed a 14% crude protein, corn-soybean meal diet was compared with that of pigs fed similar diets supplemented with 1.5 or 3% fumaric acid. PMID- 4040131 TI - Flow cytometric determination of the proportions of X- and Y-chromosome-bearing sperm in samples of purportedly separated bull sperm. AB - A rapid assay for determining the proportions of X- and Y-chromosome-bearing sperm in semen samples would benefit research aimed at sex ratio control through sperm separation. It also would be of value for quality control should a separation technique be developed. Flow cytometric methods capable of measuring sperm DNA content precisely enough to resolve and quantify the X and Y populations in many mammalian species have been developed. They are effective for fresh and cryopreserved sperm of most domestic animals. Results are reported of flow cytometric analyses of bull sperm samples from seven commercial and academic sources after processing with procedures purported to separate the X and Y populations. In no case was enrichment of either sperm population observed. Breeding trials carried out by the sources of two of the sets of samples showed these procedures were ineffective in altering the sex ratio. PMID- 4040132 TI - Penetration of aztreonam into human cerebrospinal fluid in the presence of meningeal inflammation. AB - Cerebrospinal fluid of aztreonam were measured in 11 patients with meningeal inflammation. Two to eight hours after a single 2 gm intravenous dose, CSF aztreonam levels ranged from 0.76 to 16.6 mg/l. The mean CSF concentration in four patients with viral meningitis was 1.28 mg/l, which was lower than the mean concentration of 7.2 mg/l in the five with bacterial, cryptococcal or carcinomatous meningitis. Two patients with infected subdural drains were also sampled serially and had CSF levels greater than 1 mg/l between 1 and 8 h post dose. Penetration of aztreonam into the CSF in the presence of meningeal inflammation appears adequate to warrant therapeutic trials in patients infected with susceptible organisms. PMID- 4040133 TI - In vitro modulation of differentiation by calcium in organ cultures of human and murine epithelial tissue. AB - The differentiation of epithelial tissue in organ cultures of murine buccal mucosa, various human oral mucosa, and human newborn foreskin was found to be dependent on the calcium concentration of the culture media. In low calcium medium (less than or equal to 0.07 mM) epithelial differentiation was inhibited. The original stratifying layers separate and can be removed, producing a destratified explant. Histologically such an explant consists of a dorsal epithelial layer of basal keratinocytes resting on an intact basal lamina with subjacent stroma. At 0.01 mM calcium, the epithelial layer was one to two cells thick whereas at 0.07 mM it could be three or more layers in thickness with the most superficial cells being spread over the underlying cells. In addition to differentiation, keratinocyte migration over the sides of the explant (epiboly) and epithelial proliferation as determined by [3H]thymidine autoradiography were reduced by culture in low calcium medium. Redifferentiation occurs upon return to normal calcium levels (1.8 mM); addition of hydrocortisone to low calcium media was found to facilitate this redifferentiation. PMID- 4040134 TI - Antigenic polymorphism of the LamB protein among members of the family Enterobacteriaceae. AB - In this study we demonstrate that most members of the family Enterobacteriaceae possess a maltose-inducible outer membrane protein homologous to the LamB protein of Escherichia coli K-12. These proteins react with polyclonal antibodies raised against the LamB protein of E. coli K-12. We compared the antigenic structure of the LamB protein in members of the family Enterobacteriaceae with six monoclonal antibodies raised against the LamB protein of E. coli K-12. Four of them reacted with epitopes located at the outer face of the membrane, and two reacted with epitopes located at the inner face of the membrane. A great degree of variability was observed for the external epitopes. Even in a single species, such as E. coli, an important polymorphism was present. In contrast, the internal epitopes were more conserved. PMID- 4040135 TI - The electrochemical H+ gradient in the yeast Rhodotorula glutinis. AB - The electrochemical gradient of protons, delta mu H+, was estimated in the obligatory aerobic yeast Rhodotorula glutinis in the pH0 range from 3 to 8.5. The membrane potential, delta psi, was measured by steady-state distribution of the hydrophobic ions, tetraphenylphosphonium (TPP+) for negative delta psi above pH0 4.5, and thiocyanate (SCN-) for positive delta psi below pH0 4.5. The chemical gradient of H+ was determined by measuring the chemical shift of intracellular Pi by 31P-NMR at given pH0 values. The values of pHi increased almost linearly from 7.3 at pH0 3 to 7.8 at pH0 8.5. In the physiological pH0 range from 3.5 to 6, delta mu H+ was fairly constant at values between 17-18 KJ mol-1, gradually decreasing at pH0 above 6. In deenergized cells, the intracellular pHi decreased to values as low as 6, regardless of whether the cell suspension was buffered at pH0 4.5 or 7.5. There was no membrane potential detectable in deenergized cells. PMID- 4040136 TI - Cytoplasmic motions, rheology, and structure probed by a novel magnetic particle method. AB - The motions of magnetic particles contained within organelles of living cells were followed by measuring magnetic fields generated by the particles. The alignment of particles was sensed magnetometrically and was manipulated by external fields, allowing non-invasive detection of particle motion as well as examination of cytoplasmic viscoelasticity. Motility and rheology data are presented for pulmonary macrophages isolated from lungs of hamsters 1 d after the animals had breathed airborne gamma-Fe2O3 particles. The magnetic directions of particles within phagosomes and secondary lysosomes were aligned, and the weak magnetic field produced by the particles was recorded. For dead cells, this remanent field was constant, but for viable macrophages, the remanent field decreased rapidly so that only 42% of its initial magnitude remained 5 min after alignment. A twisting field was applied perpendicular to the direction of alignment and the rate at which particles reoriented to this new direction was followed. The same twisting was repeated for particles suspended in a series of viscosity standards. Based on this approach, the low-shear apparent intracellular viscosity was estimated to be 1.2-2.7 X 10(3) Pa.s (1.2-2.7 X 10(4) poise). Time lapse video microscopy confirmed the alignment of ingested particles upon magnetization and showed persistent cellular motility during randomization of alignment. Cytochalasin D and low temperature both reduced cytoplasmic activity and remanent-field decay, but affected rheology differently. Magnetic particles were observed in association with the microtubule organizing center by immunofluorescence microscopy; magnetization did not affect microtubule distribution. However, both vimentin intermediate filaments and f-actin reorganized after magnetization. These data demonstrate that magnetometry of isolated phagocytic cells can probe organelle movements, rheology, and physical properties of the cytoskeleton in living cells. PMID- 4040137 TI - Evidence for an involvement of actin in the positioning and motility of centrosomes. AB - Cultured human polymorphonuclear leukocytes exposed to the tumor promoter 12-O tetradecanoylphorbol-13-acetate (TPA) spread on the substratum and undergo centrosome splitting. The two centrioles may separate by a distance of several micrometers, each being surrounded by an aster of microtubules. Here we show that the centriole/aster complexes are in constant, rapid motion through the cytoplasm, carrying with them some of the cytoplasmic granules while pushing aside others, or deforming and displacing the nucleus. An analysis of this unique motility phenomenon was undertaken. We show that intact microtubules are required for TPA-induced centrosome splitting and aster motility, but not for cell spreading. More importantly, disruption of the actin network inhibits both centrosome splitting and cell spreading, and even reverses splitting (induces convergence and fusion of asters) in polymorphonuclear leukocytes pretreated with TPA alone. These observations indicate the existence of a dynamic relationship between microtubules and actin networks and provide evidence for a role of actin in determining the position of the centrosome by way of interaction with the microtubules radiating from it. PMID- 4040138 TI - Efficient detection of intermediate filament proteins using a panspecific monoclonal antibody: anti-IFA. AB - Anti-IFA, a panspecific monoclonal antibody which was raised against human glial fibrillary acidic protein (GFAP), recognizes a determinant common to GFAP and all other intermediate filament proteins. This antibody can be used to identify intermediate filament proteins from both vertebrate and invertebrate tissues. Its utility in immunoblot studies of intermediate filament proteins is enhanced by using cytoskeleton extracts and protease treatment to facilitate the transfer of high molecular weight (greater than 70 000) proteins from gels to nitrocellulose membranes. PMID- 4040139 TI - Dynamic subaortic obstruction in hypertrophic cardiomyopathy: analysis by pulsed Doppler echocardiography. AB - To determine whether true obstruction to left ventricular ejection exists in patients with hypertrophic cardiomyopathy and a subaortic gradient, pulsed Doppler echocardiography was used to analyze the patterns of left ventricular emptying in 50 patients with hypertrophic cardiomyopathy (20 with and 30 without evidence of obstruction) and in 20 normal subjects. In obstructive hypertrophic cardiomyopathy, left ventricular ejection was characterized by early and rapid emptying (76 +/- 14% of aortic flow velocity in the initial one-third of systole). The proportion of forward flow velocity occurring before initial mitral septal contact (and hence, by inference before the onset of the subaortic gradient) was variable, but averaged 58%. In contrast, the proportion of forward flow velocity occurring after mitral-septal contact (and, therefore, concomitant with the gradient and increased intraventricular pressure) was considerable, averaging over 40%. Mid-systolic impedance to left ventricular outflow was suggested by the rapid deceleration in aortic flow velocity concomitant with mitral-septal contact and premature partial aortic valve closure. Furthermore, left ventricular ejection was prolonged (384 +/- 40 ms) and the ventricle continued to empty and shorten during the period when both the pressure gradient and markedly increased intraventricular pressures were present. In 16 of 20 patients, a relatively small second peak in flow velocity appeared in late systole. Since marked systolic anterior motion of the mitral valve was still present, the late systolic portion of forward flow velocity also appeared to be largely ejected during imposition of a mechanical impediment to outflow. In contrast, patients with nonobstructive hypertrophic cardiomyopathy showed no evidence of impedance to left ventricular ejection. Aortic flow velocity waveforms were similar to those of normal subjects, with flow persisting to aortic valve closure; significant mitral systolic anterior motion and partial mid systolic aortic valve closure were absent, and the systolic ejection period was normal (303 +/- 27 ms).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 4040140 TI - The mechanism of Ptychodiscus brevis toxin-induced rat vas deferens contraction. AB - Ptychodiscus brevis, which causes Florida red tide, produces Ptychodiscus brevis toxin (PBTX) known to contain neurotoxins and to induce rhinorrhea, tearing, and cough in normal humans and wheezing in asthmatic subjects. It was previously reported (J Allergy Clin Immunol 69:418, 1982; 73:824, 1984) that PBTX causes canine tracheal smooth muscle contraction via stimulation of sodium channels in the axons of parasympathetic postganglionic nerves and the release of acetylcholine from these nerve endings. This was postulated to be an asthma triggering mechanism. In this article the toxins were evaluated to determine if they also stimulate sodium channels on adrenergic nerve endings and release norepinephrine. Rat vas deferens was selected as the experimental tissue. Both PBTX and norepinephrine contracted rat vas deferens. Prazosin 10(-6) mol/L blocked the response to PBTX (3 micrograms/ml) (88.3% to 27.3% contraction [n = 6; p less than 0.001]) and the response to norepinephrine (EC50 was shifted from 1.67 X 10(-6) mol/L to 1.25 X 10(-4) mol/L in the presence of prazosin 10(-6) mol/L [n = 6; p less than 0.001]). Phentolamine 10(-6) mol/L also blocked both PBTX and norepinephrine. Tetrodotoxin 10(-7) mol/L, a sodium channel blocker, completely blocked the response to PBTX but not to norepinephrine. The response to PBTX was significantly reduced from 1.53 gm of tension in controls to 0.29 gm of tension (n = 6; p = 0.002) in tissues obtained from rats pretreated with reserpine (2 mg/kg per day for 2 days, injected intraperitoneally). Verapamil 10( 5) mol/L blocked the PBTX response, and PBTX caused no contraction in calcium free media.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4040141 TI - [Retinal detachment: temporary internal tamponade with silicone oil after vitrectomy. Anatomic and functional results]. AB - Forty-seven patients with retinal detachment treated by vitrectomy and silicone oil injection benefited from semi-premature ablation of the oil: after a mean of 5 months for supple retinal detachments and 6 1/2 months for those associated with vitreoretinal proliferation. Ablation was performed after obtaining a solid chorioretinal scar by cryopexy or endodiathermy, usually combined with laser panphotocoagulation. The technique used for ablation is described. After follow up for from 9 months to 3 1/2 years (mean 18 months) two-thirds of the patients had flat retinas. Recurrences developed usually during the first month. An explanation for these relapses is proposed. PMID- 4040142 TI - [Acute necrotizing retinitis. Apropos of 2 cases]. AB - Two cases of acute retinal necrosis are reported, the etiology of this affection being priorly defined. The lesions were bilateral in the first case, and retinal detachment developed: the first eye was inoperable, and surgery was unsuccessful for the second eye in spite of a salvage vitrectomy after a classical operation. We therefore treated the second case with immediate and massive corticotherapy, and, mainly, preventive total vitrectomy as soon as the first signs of vitreous retraction appeared and before the occurrence of retinal detachment. This preventive vitrectomy, not previously described to our knowledge, seems to provide favorable results. PMID- 4040143 TI - [Evolution of plasma levels of SHBG (sex-hormone binding globulin) during ovulation induction using gonadotrophins]. AB - The plasma levels of proteins bound to steroids come under the influence of the levels of estrogens. This is why we have studied the changes in plasma SHBG in sterile women who were being treated by gonadotropins (HMG-HCG). The plasma level of SHBG was worked out using Laurell's electroimmunoassay technique with an autoradiographic display using estradiol labeled with I.125. It only takes 48 hours contact with radio films. Out of 12 patients 9 responded to the treatment as demonstrated by the plasma levels of estradiol (E2) and progesterone (P). We have found that in these women there was a rise in plasma SHBG which was significant from the 7th day of the treatment onwards (3.7 +/- 1.7 mg/l as against 5.9 +/- 2.6 mg/l, p less than 0.01) and this reached nearly twice the base level when E2 reached its maximum level (6.4 +/- 2.7 mg/l). When treatment was stopped the plasma level of SHBG dropped to that of the follicular phase, but it was out of step with the plasma E2 levels. The index of free E2 as compared with E2/TEBG showed a close superimposition when compared with the levels of E2 obtained using a radioimmunological method. This fact reinforces the value of plasma E2 as the way of monitoring the effect of induction of ovulation. Our overall conclusion is that a marked and rapid change in the level of plasma E2 directly influences the level of plasma SHBG. The consequences for treatment are that it is important to respect as far as possible the physiological conditions that are present when induction of ovulation is undertaken. PMID- 4040144 TI - [Small oscillations in fetal cardiac rhythm: a sign of well-being? A new approach to the diagnostic value of spontaneous recordings of fetal cardiac rhythm in pregnancy]. AB - The authors suggest an indirect evaluation of the electrocortical activity of the fetus by looking at evidence of cyclical variations in fetal cardiac rhythm. These are shown up by periodic changes in the variability of the rhythm. The narrow association that has been established between small changes in episodes of cardiac rhythm and deep sleep--which is itself evidence of satisfactory cortical development--make this type of tracing, under certain conditions, an excellent sign of fetal wellbeing. This means that the value of small variabilities in fetal heart rhythm takes on greater importance as a prognostic feature. PMID- 4040145 TI - Effects of specific antibodies, hormones, and lipoproteins on bacterial lipopolysaccharides injected into the rat. AB - When gram-negative lipopolysaccharides (LPS) are injected intravenously into experimental animals, approximately one-third of the LPS bind to high-density lipoproteins (HDL) in the plasma and are slowly taken up into tissues by HDL mediated mechanisms. Molecules of LPS in the plasma that do not bind to HDL are taken up more rapidly by tissues that are rich in phagocytic cells (e.g., liver, spleen). In these experiments we evaluated the effects of several potential host factors on the binding of LPS to HDL and on the tissue uptake of LPS injected intravenously into rats. Antibodies to LPS inhibited LPS binding to HDL and increased the uptake of the injected LPS (as well as the LPS in preformed LPS-HDL complexes) by the liver and spleen. High levels of circulating HDL decreased the uptake of injected LPS and LPS-HDL complexes by the adrenal gland, presumably by occupying tissue receptors for HDL. Pretreating rats with dexamethasone unexpectedly decreased the uptake of injected LPS-HDL complexes by the adrenal gland and increased uptake of LPS by the gland, a result suggesting that this drug has opposing effects on the uptake of HDL-bound and -unbound LPS by the adrenal gland. The host factors studied appear to influence the fate of injected LPS by acting at different sites: IgG antibody to LPS blocks the binding of LPS to HDL in the plasma, whereas all of the factors studied have effects that modulate the uptake of LPS or LPS-HDL complexes or both by the cells of specific tissues. PMID- 4040146 TI - Chromosomal aberrations in muntjac cells resulting from exposure to interferon. AB - Cells of the Indian deer (Muntiacus muntjac) are sensitive to the antiviral and antiproliferative action of human beta-interferon (beta-IFN). Because of their low diploid chromosome number and readily identifiable chromosomes, they provide a convenient model system in which to test for the ability of IFN treatment to result in chromosome abnormalities. Increases in the frequencies of chromosome gaps and breaks have been observed after 72 h of treatment with IFN at a concentration of 100 U/ml. At IFN concentrations of 10-100 U/ml, there is a higher proportion of aberrations in the X chromosome than would be expected in a random distribution. At 1,000-1,700 U/ml IFN, there is an increase in the proportion of cells with multiple abnormalities over that observed at 0-100 U/ml IFN, and the distribution of aberrations appears to be random. PMID- 4040147 TI - Long-term ventilation of the middle ear using the Goode T-tube. PMID- 4040148 TI - Psychosexual factors in infertility. PMID- 4040149 TI - Plant tRNA genes: putative soybean genes for tRNAasp and tRNAmet. AB - We have identified cloned fragments of the soybean genome that hybridize to total soybean tRNA. Five of these clones, chosen at random, have unique patterns of restriction endonuclease sites and contain only a small region that is homologous to tRNA (less than 1 kb of 10-12 kb cloned). Two of the hybridizing fragments were subcloned and regions of about 600 bp including the homologies were sequenced. Each region contains a single putative tRNA gene, for tRNAasp or tRNAmet, surrounded by DNA rich in AT basepairs (68-82%). Neither sequence encodes the amino acid-accepting -CCA terminus. The tRNAasp gene does not contain any intervening sequences, but the tRNAmet gene has an 11-bp sequence in the anticodon loop that would not be expected in the mature tRNA. There appear to be a small number of sequences within the soybean genome that share homology with each of the regions containing a putative tRNA gene. PMID- 4040150 TI - Mortality from congenital malformations by mother's country of birth. AB - Mortality from congenital malformations by mother's country of birth was examined in England and Wales between the years 1976 and 1980, based on stillbirths and infant deaths. There were 18 870 stillbirths and infant deaths attributed to congenital malformations in this period, of which 2 375 (13%) were to mothers born outside the United Kingdom. There were excess deaths from malformations among Pakistani, Indian/Bangladeshi, African, and Irish mothers. In contrast, West Indian mothers had a consistent deficit in deaths from malformations over the study period. The significance of these findings is discussed. PMID- 4040151 TI - Pregnancy and its outcome among hospital personnel according to occupation and working conditions. AB - Relationships between occupation, working conditions, and the development and outcome of pregnancy were analysed on a sample of women employed in hospital during their pregnancy. Ancillary staff members experienced more uterine contractions during pregnancy, more preterm deliveries, and more low birthweight infants than those performing other duties; this remained true after adjusting for social characteristics. The rate of preterm delivery was significantly higher in the presence of at least two of the following arduous working conditions: stand-up work, carrying heavy loads (exclusive of patients), and heavy cleaning tasks; this was so, whatever the occupation. PMID- 4040152 TI - Comparison of birthweight and infant mortality between Singapore and England and Wales, 1980. AB - For 1980 Singapore was found to have overall a more favourable birthweight distribution than England and Wales. The proportion of very low birthweight babies (less than 1500 g) and heavy babies (3500 g and over) was 0.4% and 18.5% in Singapore and 0.7% and 34.9% in England and Wales for live births, and 0.6% and 18.5% against 0.9% and 34.7% for total births. However, for low birthweight (less than 2500 g) Singapore with 7.5% in live births and 7.9% in total births had higher rates than England and Wales (6.7% and 7.2%). While infant mortality rates were very similar, Singapore had a somewhat higher neonatal mortality rate but a considerably lower postneonatal mortality rate than England and Wales. The effects on mortality of standardising for birthweight are examined. The problems of interpretation and the implications of the findings are discussed. PMID- 4040153 TI - Hidden autoantibodies against common serum proteins in murine systemic lupus erythematosus. Detection by in vitro plaque-forming cell assay. AB - The autoantibodies found in human and murine systemic lupus erythematosus (SLE) are generally directed against cells or components of cells such as nuclear antigens. This predilection may be due to the unusual immunogenicity of certain autoantigens, or to unusual patterns of antibody crossreactivity. Alternatively, the observed spectrum of reactivities may reflect the in vivo absorption of those autoantibodies directed against soluble antigens. To test whether hitherto undetected autoantibodies against serum proteins might exist in murine SLE, we developed assays that were independent of the possibility of absorption of autoantibodies by serum autoantigens; large numbers of plaque-forming cells (PFC) directed against mouse albumin and mouse transferrin were easily detected in the spleens of MRL/Mp-lpr/lpr, BXSB, and NZB mice. The secreted antibodies were relatively specific for the mouse proteins, since only limited cross-reactivity was seen with albumin and transferrins of other species in inhibition experiments. The production of these hidden antibodies could not be the result of diffuse polyclonal B cell activation, since the PFC to mouse transferrins and albumin were not always accompanied by comparable numbers of PFC against related albumins and transferrins. The results indicate that autoantibody production in murine lupus is a generalized phenomenon, not limited to the production of autoantibodies to nuclear or other cell-bound antibodies. However, the relative specificity of the autoantibodies for self-antigens indicates that diffuse polyclonal B cell activation cannot be the mechanism responsible, and argues that a selective mechanism, probably driven by antigen, accounts for production of autoantibodies in SLE. PMID- 4040154 TI - Antibacterial sesquiterpene aryl esters from Armillaria mellea. AB - Investigation of the mycelial extract of Armillaria mellea led to the isolation of the known melleolide (2a) and two new sesquiterpene aryl eters, 4-O methylmelleolide (2b) and judeol (1c). Their structures were deduced from spectral data and that of (2b) confirmed by X-ray analysis. The new esters (1c) and (2b) showed strong antibacterial activity against gram-positive bacteria. PMID- 4040155 TI - Induction of neurofibrillary tangles in cultured mouse neurons by maytanprine. AB - Neurofibrillary (neurofilament) tangles were induced in cultured neurons of newborn mouse dorsal root ganglia by exposure to maytanprine, an anti-microtubule drug. By 12-24 h of treatment, small short neurofilament bundles were found in the neuronal perikarya and proximal portions of the neurites. By 48-72 h of treatment, small neurofilament bundles were assembled into larger masses, and after 72 h and onward several neurofilament bundles coalesced into single large distinctive perinuclear rings in the neuronal perikarya. A histometric analysis of maytanprine treated axons demonstrated that the density of microtubules decreased rapidly, while that of neurofilaments decreased more slowly. As a result of microtubule depolymerization by maytanprine treatment, neurofilaments change their distribution pattern in neuronal perikarya and subsequently form tangles. PMID- 4040156 TI - Morphologic effects of ammonia on primary astrocyte cultures. II. Electron microscopic studies. AB - Light microscopic studies of primary astrocyte cultures following exposure to ammonia have shown several alterations. To determine the nature and significance of these changes, electron microscopic studies were performed. Ultrastructural changes consisted of proliferation, pleomorphism and swelling of mitochondria, condensation of the mitochondrial matrix, cytoplasmic lucency and vacuolization, disaggregation of polyribosomal clusters, an initial increase followed by degranulation of rough endoplasmic reticulum, proliferation of smooth endoplasmic reticulum, an accumulation of dense bodies and a loss of intermediate glial filaments. The early alterations appeared reactive and perhaps reflected ammonia detoxification. Some changes were degenerative and support the view that ammonia exerts a direct toxic effect on astrocytes. It is postulated that these changes may interfere with critical astroglial functions and thereby play a key role in the neurologic dysfunction seen in hyperammonemia. PMID- 4040157 TI - Fine structure of anterior horns in patients without amyotrophic lateral sclerosis. AB - Light and electron microscopic study of the anterior horns in nine patients without amyotrophic lateral sclerosis (ALS) disclosed several features usually described in ALS. Central chromatolysis and spheroids with fine structure identical to that seen in ALS were observed in three cases. Rare honeycomb-like structures, dense filamentous aggregates, dense granular deposits, stubby mitochondria and membrane-bound aggregates of spherical and tubular particles were also observed. No typical Bunina bodies or focal argyrophilia of the chromatolytic neurons were found. PMID- 4040158 TI - Lorazepam in cancer patients treated with cisplatin: a drug having antiemetic, amnesic, and anxiolytic effects. AB - There currently is no pharmacologic approach to the problem of anticipatory nausea and vomiting (ANV). Lorazepam (Ativan, Wyeth Laboratories, Philadelphia) is an interesting candidate drug if it could block the recall of the unpleasant events associated with chemotherapy, especially if it also has antiemetic properties. Since ANV is a conditioned (learned) response, it may well depend on a memory imprint of the stimulus. This pilot study was designed to use intravenous lorazepam given before and after cisplatin infusion in 32 patients, and to make detailed measurements of nausea, vomiting, recent memory, anxiety, and sedation as well as toxicity. Satisfactory responses occurred in about 70%, as rated separately both by investigator and patient. Forty-six percent did not even recall receiving chemotherapy, regardless of whether or not they vomited; 80% had no significant anxiety after chemotherapy. Adverse reactions included some cases of perceptual disturbance, urinary incontinence, diarrhea, hypotension, and one case of severe transient amnesia. No long-term adverse effects were noted. PMID- 4040159 TI - Spatial distribution of retinol-binding protein and retinyl palmitate hydrolase activity in normal and vitamin A-deficient rat liver. AB - A study was conducted to explore the spatial distribution within rat liver of two proteins importantly involved in retinoid metabolism in liver, namely, retinol binding protein (RBP) and the enzyme retinyl palmitate hydrolase (RPH). The study was conducted with both vitamin A-sufficient (control) and vitamin A-deficient rats. Livers were carefully and reproducibly dissected into 11 sections each, and RBP levels and RPH activities were measured for each section homogenate. Both RBP and RPH activity displayed highly significant spatial heterogeneity in their distributions in liver. For control rats, the mean level of RBP was 39.0 micrograms/g wet weight, with a section-to-section variation of 14.5. For deficient rats, the corresponding RBP mean and variation values were 283 and 56 micrograms/g wet weight. For RPH, the mean level was 136 pmol free fatty acids (FFA) formed/(min X mg) with a section-to-section variation of 178. Both inspection of the data and analysis of variance indicated that this significant section-to-section variation (spatial heterogeneity) did not follow a consistent anatomic pattern from rat to rat. Thus, no one specific anatomic location in the liver was consistently high or low with regard to either RBP or RPH. Since the spatial distributions of both RBP and RPH activity did not follow a consistent anatomic pattern, it is not possible to obtain an accurate measure of the total liver levels for either parameter in a homogenate made from a small section. Finally, the patterns of distribution of RBP and RPH activity observed in the liver sections from both vitamin A-sufficient and deficient rats were not significantly correlated, either directly or inversely, as determined by chi square analysis. Thus, RBP and RPH activity levels vary independently of each other in their heterogeneous anatomic distributions in rat liver. PMID- 4040160 TI - [Long-term result of grommets in children with secretory otitis media]. PMID- 4040161 TI - [Evaluation of eustachian tubal functions in patients with otitis media with effusion]. PMID- 4040162 TI - Steroid therapy of neonatal ITP. PMID- 4040163 TI - Low levels of sex hormone--binding globulin in obese children. PMID- 4040164 TI - Bovine thelaziasis in Iowa. AB - The prevalence of developing Thelazia nematodes in face flies (Musca autumnalis) was studied for 7 yr at a beef farm in central Iowa. Juvenile nematodes were not found among flies in reproductive diapause in autumn, nor among nulliparous, overwintered flies in spring, but only among actively reproducing insects. Thus Thelazia probably do not overwinter in face flies. A mean prevalence of 2.0% infected was recorded among flies in 7 fly breeding seasons. No heterogeneity in Thelazia prevalence was detected within fly breeding seasons. The frequency distribution of Thelazia among face flies by year of occurrence was homogeneous, with a mean of 2.75 larval nematodes per infected fly. Thelazia gulosa and T. skrjabini were recovered in necropsy from the eyes of bovines from central Iowa. Prevalence among fat cattle 18-27 mo old was 15%; among cows 3-15 yr old, prevalence was only 3%. Thelazia skrjabini was found in 29 eyes and T. gulosa in 4 eyes. Infections were randomly distributed among the eyes of subject cattle. The mean worm burden was 2.3 T. skrjabini and 12 T. gulosa per infected eye. Thelaziasis is clearly enzootic in Iowa. PMID- 4040165 TI - In vitro transformation of Schistosoma japonicum miracidia to young sporocysts in a culture system for egg maturation. PMID- 4040166 TI - Temperature-induced separation of larvae of Uncinaria stenocephala from a mixed fecal culture containing Ancylostoma caninum. PMID- 4040167 TI - Hydrops fetalis associated with midgut volvulus. PMID- 4040168 TI - [Effect of phosphate and inhibitors of protein synthesis on the growth and tentoxin production of Alternaria alternata (Fr.) Keissler]. AB - The synthesis of a phytotoxic substance, tentoxin, by Alternaria alternata (Fr.) Keissler is negatively controlled by inorganic phosphate. We show here that the influence of phosphate on the production of this secondary metabolite is time dependent. By using inhibitors of protein synthesis (p-fluorphenylalanine, cycloheximide) together with a resuspension technique, attempts were made to find out when the enzymes responsible for tentoxin synthesis are formed. PMID- 4040169 TI - Effect of chronic methadone administration on neuroendocrine function in young adult rats. AB - This study reports the endocrine effects of chronic methadone (METH) administration. Two treatment regimens were tested: a constant (5 mg/kg/day, CD) or increasing dose (5 mg/kg twice daily, increasing 1 mg/kg/day, ID). Basal hormone levels and endocrine responses to opiate challenge were determined on days 5, 10 and 20 and after withdrawal. METH effects on hormone secretion varied with treatment duration, dose and hormone. Tolerance to METH effects on corticosterone (CS), prolactin (PRL), growth hormone (GH), thyroid-stimulating hormone (TSH) and luteinizing hormone (LH) developed during the ID regimen and basal CS, TSH and LH levels were altered. In addition, serum testosterone, T3 and T4 decreased significantly during this regimen. In contrast, only CS secretion was affected markedly by the CD regimen. Resting levels were elevated by day 5 and the CS response to acute METH challenge was reversed. Tolerance also developed to METH-induced TSH suppression, but only with longer treatment. Similarly, basal TSH and LH levels were affected only with longer treatment. Basal PRL, GH and LH levels and LH, PRL and GH responses to acute METH challenge were not affected by the CD regimen. Changes in basal CS and TSH levels observed in these studies probably reflect abstinence, as even more pronounced changes occurred after naloxone-precipitated abstinence and suppressed rather than reversed responses were observed if animals were withdrawn for 36 hr before testing. Tolerance in some endocrine systems appears to be quite long-lasting, as CS, TSH and PRL responses to METH challenge were still decreased 3 weeks after withdrawal from the ID regimen.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4040170 TI - Species of the coccidian genus Alveocystis. AB - Publications on the coccidia of certain invertebrates are reviewed and two new taxonomic-nomenclatural combinations are introduced: Alveocystis macrocoronata (Luling, 1942) n. comb., in hosts Priapulus caudatus and Halicryptus spinulosus (Priapuloidea); and A. gugleri (Wacha, 1981) n. comb., in Triodopsis albolabris (Mollusca). PMID- 4040171 TI - Comparison of the radiosensitivity of dry dormant eggs, gemmules, and statoblasts of three invertebrate forms. PMID- 4040172 TI - Seckel syndrome: an overdiagnosed syndrome. AB - Five children in whom a diagnosis of Seckel syndrome had previously been made were re-examined in the genetic unit. One child had classical Seckel syndrome, a sib pair had the features of the syndrome with less severe short stature, and in two children the diagnosis was not confirmed. Seckel syndrome is only one of a group of low birth weight microcephalic dwarfism and careful attention should be paid to fulfillment of the major criteria defined by Seckel before the diagnosis is made. There remains a heterogeneous group of low birth weight microcephalic dwarfism yet to be defined. PMID- 4040173 TI - Phenotypic delineation of ring chromosome 15 and Russell-Silver syndromes. AB - A male child with features of the Russell-Silver syndrome, including pre- and postnatal growth delay, triangular facies, bilateral fifth finger clinodactyly, and disproportionate lower extremities, was found to have a ring chromosome 15 in all peripheral leucocytes examined. Review of the reported cases of ring chromosome 15 defines a malformation syndrome with a characteristic facies related to deletion of the 15q26.2----qter region. Russell-Silver and ring 15 syndromes share clinical features such as growth deficiency, triangular facies, digital anomalies, and cafe-au-lait spots. Microcephaly, mental retardation, facial dysmorphology, limb anomalies, and cardiac defects are more striking in ring chromosome 15 patients and are indications for karyotyping when found in conjunction with the Russell-Silver phenotype. PMID- 4040174 TI - Medical students' opinions on economic aspects of the health care system. AB - Responses of 423 freshmen and 410 seniors at Jefferson Medical College in 1980-81 and 1982-83 to 15 questions on economic aspects of the health care system were compared. A majority of the students considered the cost of medical care, the cost of medical education, malpractice claims, and the failure of individuals to assume responsibility for their health to be major problems. A majority of the seniors also considered excessive government influence on the financing of medical care a major problem. More freshmen than seniors favored national health insurance and health maintenance organizations. More seniors than freshmen supported the professional standards review organization concept and action to discourage increases in the supply of physicians. Concern about the number of physicians entering the profession increased among seniors between 1981 and 1983. The data suggest that at graduation the students were more concerned about the position of physicians but might not be more informed about important aspects of the functioning of the health care system than they were at entry. PMID- 4040175 TI - Isolation and characterization of an alphoid centromeric repeat family from the human Y chromosome. AB - A collection of human Y-derived cosmid clones was screened with a plasmid insert containing a member of the human X chromosome alphoid repeat family, DXZ1. Two positive cosmids were isolated and the repeats they contained were investigated by Southern blotting, in situ hybridization and sequence analysis. On hybridization to human genomic DNAs, the expected cross-hybridization characteristic of all alphoid sequences was seen and, in addition, a 5500 base EcoRI fragment was found to be characteristic of a Y-specific alphoid repeat. Dosage experiments demonstrated that there are about 100 copies of this 5500 base EcoRI alphoid fragment on the Y chromosome. Studies utilizing DNA from human mouse hybrids containing only portions of the Y chromosome and in situ hybridizations to chromosome spreads demonstrated the Y centromeric localization of the 5500 base repeat. Cross-hybridization to autosomes 13, 14 and 15 was also seen; however, these chromosomes lacked detectable copies of the 5500 base EcoRI repeat sequence arrangement. Sequence analysis of portions of the Y repeat and portions of the DXZ1 repeat demonstrated about 70% homology to each other and of each to the human consensus alphoid sequence. The 5500 base EcoRI fragment was not seen in gorilla, orangutan or chimpanzee male DNA. PMID- 4040176 TI - Postnatal taurine deficiency in the kitten results in a persistence of the cerebellar external granule cell layer: correction by taurine feeding. AB - Dietary deprivation of taurine in pregnant cats from approximately 1 week prior to giving birth is sufficient to reduce substantially the taurine concentration in feline milk but does not result in any abnormalities in kittens at birth. Kittens nursing on this low taurine milk have a lower growth rate than normal, have lower tissue taurine concentrations, and 8 weeks after birth have a persistence of cells in the cerebellar external granule cell layer. Mitotic figures are present also, indicating that cell division is occurring still, an event which normally is completed 3-4 weeks after birth. Daily oral supplementation with 40 mumoles taurine increases the growth rate almost to the level of normally nurtured kittens and results in normal tissue taurine concentrations and apparently normal migration of cells in the cerebellum. These findings indicate that nutritional taurine supplied in the milk is involved in the normal ontogeny of the cerebellum and that a taurine deficiency at this stage of development results in a maturational delay. PMID- 4040177 TI - The echocardiographic diagnosis of multiple fetal cardiac tumors. PMID- 4040178 TI - Horseshoe kidney in one of identical twin girls. AB - We report on a 5-month-old female twin who presented with urinary tract infection and was found to have a horseshoe kidney. Her identical twin had a normal renal anatomy. There have been only 2 other reports of a horseshoe kidney in monozygotic twins: in 1 instance both twins were affected, while in the other there was discordance. PMID- 4040179 TI - Development of nongerm cell malignancies in nonseminomatous germ cell tumors. AB - We report 2 cases of sarcomatous transformation of mixed germ cell tumors of the testis. Both patients received cisplatin-based combination chemotherapy. Embryonal rhabdomyosarcoma, chondrosarcoma and spindle cell sarcoma were the dominant pathological patterns in the metastatic sites. Nongerm cell malignancies in mixed germ cell tumors following chemotherapy may be more common than previously described. PMID- 4040180 TI - Re: Vesicourethral motility following acute spinal cord transection in the cat. PMID- 4040181 TI - Dynamic shape of the female urethra during micturition. Clinical methods. AB - Densitometry of the x-ray image provides a suitable technique for clinical quantification of the urethral shape during all stages of voiding. The technique of cystourethrographic densitometry is applied to determine the cross-sectional shape of the human female urethra during various phases of voiding. Errors that may occur because the x-rays are not perpendicularly incident to the urethral plane are considered and a method for their minimization is indicated. PMID- 4040182 TI - Number and size of myocytes, amount of interstitial space and extent of disarray of the hearts in patients with systemic hypertension and asymmetric septal hypertrophy. AB - Wall thickness, the extent of disarray, the number and the size of myocytes and the amount of interstitial space were measured in the ventricular septum (VS) and left ventricular (LV) free wall in hearts of 6 patients with chronic systemic hypertension and asymmetric septal hypertrophy (ASH). Twenty-five subjects (15 with no cardiac disease, and 10 with systemic hypertension) without ASH served as the controls. In the six patients with ASH, the degree of ASH ranged from 1.3 to 1.6. The extent of disarray in VS was 20% in one heart and within normal limits (mean +/- SD = 3 +/- 3%) in the other 5. The size of myocytes increased both in the VS and LV free wall and the VS/LV ratio ranged from 0.9 to 1.0. There was no significant difference in the % area of interstitial space between hearts with ASH and controls, and the VS/LV ratio ranged from 0.9 to 1.1. The number of transmural muscle layers (number of myocytes) was 680 +/- 90 in the VS and 440 +/ 40 in the LV free wall of these with ASH, and 500 +/- 60 in the VS and 490 +/- 60 in the LV free wall of control subjects. The VS/LV ratio of the number of myocytes ranged from 1.3 to 1.7 and was correlated with the VS/LV ratio of wall thickness. Although the sample is small, our findings suggest that most hearts from patients with chronic systemic hypertension and ASH have no diffuse disarray in the VS and that ASH probably occurs secondary to pressure overload.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4040183 TI - [Perioperative management of hypertrophic obstructive cardiomyopathy by using continuous propranolol infusion]. PMID- 4040184 TI - Various types of systolic clicks in patients with muscular subaortic stenosis. AB - Four clinical cases of subaortic hypertrophic muscular stenosis are discussed. All four, in addition to a loud systolic murmur, had a loud systolic click. However, the timing of the click and its relationship to the phase of the carotid pulse were different in each case varying from close to medium and to distant (or midsystolic). The comparison of the sound tracing with the carotid tracing demonstrated that, in each case, a sudden change in acceleration was taking place. In one, the click coincided with the onset of the carotid upstroke; in another, with the first peak of the carotid pulse; in the third, with the trough between first and second peak of the pulse; in the last, with a sudden drop of the pulse at mid-systole caused by sudden obstruction to flow. It is concluded that the clicks were caused by rapid changes of acceleration resulting from the abnormal aortic ejection. Thus, the study of the carotid pulse and of the sound tracing are important for a non-invasive diagnosis together with the echo study of the septum and ventricular wall. PMID- 4040185 TI - [Thymic humoral factor produced by a thymic epithelial culture]. PMID- 4040187 TI - Effects of age, milking and season on magnesium, calcium and inorganic phosphorus metabolisms in cows. PMID- 4040186 TI - [Complete response of advanced bladder carcinoma to chemotherapy alone proved by histological examination of the surgical specimen: a case report]. PMID- 4040188 TI - Circadian variation of ova excretion, proteinuria, hematuria, and leukocyturia in urinary schistosomiasis. AB - Urine samples from five boys (7 to 9 years) with urinary schistosomiasis were collected at 6 A.M. and thereafter at 3-hr intervals until 9 P.M. on 5 consecutive days. Ova excretion in the urine, proteinuria (PU), erythrocyturia (EU), and leucocyturia (LU) were assessed quantitatively. Egg excretion followed a circadian rhythm with a peak at 12 noon and was paralleled closely by pathological PU. Maximal erythrocyturia occurred at 6 P.M., whereas leucocyturia revealed two distinct peak times. Taking the congruent patterns of egg excretion and PU together with the results of qualitative urinary protein analysis into account, it was concluded that PU was linked causally to ova excretion and could be explained by bleeding and exudation of serum proteins during penetration of ova through the bladder mucosa. In contrast, EU and LU seemed to be caused by different pathological mechanisms. EU followed a time-delayed circadian rhythm, possibly induced by persistent bleeding, whereas LU may have indicated a concomitant inflammatory component of the bladder. PMID- 4040189 TI - Kinetics of cellular proliferation after arterial injury. II. Inhibition of smooth muscle growth by heparin. AB - Heparin inhibits intimal thickening after arterial injury. Whether this effect is due to inhibition of medial smooth muscle cell (SMC) migration, SMC proliferation in the intima, or synthesis and deposition of connective tissue has not been evident. In this study we have investigated these possibilities in a rat carotid balloon injury model. Heparin (0.3 mg/kg/hour) was administered intravenously by means of osmotic pumps to experimental animals, and controls received lactated Ringer's solution. Smooth muscle proliferation (thymidine index), intimal smooth muscle accumulation, and endothelial regeneration were measured at intervals between 0 and 28 days. Total smooth muscle growth as determined biochemically at 14 days was markedly inhibited by heparin if the pumps were placed 24 hours before or at the time of injury and less so if inserted 48 or 96 hours after injury. SMC thymidine indices were maximal in the media at 4 days and in the intima at 7 days for injured arteries of both heparin-treated and control rats; at each time point SMC proliferation and intimal thickening were less in heparin treated rats. The volume of connective tissue in the intima was the same in both groups at 28 days. Medial SMC migration into the intima was diminished by heparin treatment, but endothelial regeneration was not affected. These results support the hypothesis that heparin is a specific inhibitor of SMC migration and proliferation and is most effective if started before SMC enter S-phase. PMID- 4040192 TI - Can neonatal beta-adrenergic stimulation prevent the effects of androgenization in female rats? AB - A 25 micrograms dose of testosterone propionate injected at 4 days of age induced 90% anovulation at 100 days of age. The systemic administration of orciprenaline (8 or 16 micrograms) or yohimbine (100 micrograms) did not prevent androgenization. Twenty-five or fifty micrograms of orciprenaline injected intraventricularly reduced only partially (to 54 and 67% respectively) the effectiveness of androgenization. We concluded that beta-adrenergic receptor stimulation had a very limited ability to prevent androgenization, since the beta stimulation obtained directly with orciprenaline prevented androgenization to a very limited extent, while the possible indirect stimulation through an increase in norepinephrine endogenous release by alpha-2 receptor blocker yohimbine was ineffective. PMID- 4040191 TI - A theoretically sound and practicable equilibrium dialysis method for measuring percentage of free testosterone. AB - Free testosterone measured in serum equilibrated in vitro is considered a good index of biologically available testosterone even though a large part of free testosterone in vivo is derived locally from rapid dissociation of testosterone bound to albumin. The most accurate method for measuring free testosterone, however, is unsettled. The classical method--equilibrium dialysis--has been questioned because of the dilution of serum that it entails and the previous inability to achieve identical results with diluted and undiluted serum. Essentially identical measurements of free testosterone were achieved in diluted and undiluted charcoal-stripped serum by using the dialysis method and calculation reported here. The measured free testosterone in undiluted whole serum from women was only 4-6% lower than the estimated physiological values. These results were obtained using a validated calculation, controlling pH, using physiological bicarbonate buffer at 37 degrees C, maintaining a constant free ligand concentration for dilutions, measuring the water gain by the dialysis bag, and using highly purified labeled testosterone. The mean free testosterone for normal women was 0.17 ng/dl (0.11-0.23) and for hirsute women was 0.49 ng/dl (0.27-0.71). The testosterone not bound to testosterone-estradiol binding globulin, calculated from free testosterone and albumin concentrations, was close to the production rate/min of testosterone. The method should be adaptable to other ligands. PMID- 4040190 TI - Progesterone control of nuclear estrogen receptor: demonstration in hamster uterus during the estrous cycle and pseudopregnancy using a new exchange assay. AB - Our previous studies showed that total nuclear estrogen receptor (Re) can be extracted and measured by exchange using 10 mM pyridoxal-5'-phosphate (PLP) at low temperature (0-4 degrees C). In order to further validate the PLP assay, we measured the Re concentration in uterine cytosol and nuclei by this method under physiological conditions, i.e. during the hamster estrous cycle and pseudopregnancy. In addition, we compared the Re results obtained by the PLP method with those obtained with two other assay procedures, i.e. the KCl and NaSCN methods. During the follicular phase of the estrous cycle, all three methods showed an elevation of nuclear Re in parallel with the increase in serum estradiol (E). However, the quantity of nuclear Re obtained with the PLP method was significantly greater than with the KCl method during the follicular phase. The surge of serum progesterone (P) during the ovulatory phase of the estrous cycle was followed by a dramatic fall in nuclear Re, and the greatest loss of nuclear Re during the ovulatory phase of the cycle was detected with the PLP and NaSCN methods. On a DNA basis, cytosol Re increased significantly between Day 3 and proestrus and subsequently fell during the ovulatory phase of the cycle. P treatment of proestrus hamsters resulted in a rapid (less than 4 h) loss of nuclear Re with little or no change in cytosol Re. Chronic P exposure during pseudopregnancy with serum E maintenance, resulted in a significant suppression of both cytosol and nuclear Re. Following P withdrawal, both cytosol and nuclear Re rose significantly (less than 4 h), indicating that this effect of P was readily reversible. The results demonstrate that the Re detected under physiological conditions by the PLP method responds to both E action and P action, and that the PLP assay provides a greater recovery of Re as compared to the KCl assay. PMID- 4040193 TI - Inherited factors in leukaemia and lymphoma. PMID- 4040194 TI - A chronic arterial and venous cannulation method for freely moving rats. AB - A chronic arterial and venous cannulation method appropriate for pharmacokinetics studies in freely moving rats is described. Two catheters were implanted: one in the abdominal aorta, the other in the inferior vena cava. Passing subcutaneously, the catheters then emerged at the nape of the neck and were sealed by heating. In most cases (70%), 2-3 weeks after surgery, there were no problems of catheter patency. Twenty-four hours after surgery, all the animals were in good health as attested by normal behaviour and physiological parameters. Plasma corticosterone levels (544 +/- 219 ng/ml) determined at various times after an i.v. injection of saline, though 2.4-fold lower than in restrained rats (1330 +/- 292 ng/ml), were, however, indicative of a moderate stress. From a differential analysis of the factors involved in the relatively elevated circulating corticosterone as compared to basal levels, it is concluded that a prolonged postoperative period (7 days) and maintaining of the animals in metabolic cages are necessary conditions to obtain a minimal state of stress with this technique. PMID- 4040195 TI - Virus-induced demyelination in mice: "dying back" of oligodendrocytes. AB - Demyelination was produced in mice by intracerebral inoculation of Theiler's murine encephalomyelitis virus. The earliest ultrastructural changes occurred in the inner cytoplasmic tongues of oligodendrocytes, the most distal extension of these cells. Viral antigen was localized to glial loops that connect with myelin lamellae. This study indicates that a "dying-back" process may occur in virus infected oligodendrocytes, which then results in demyelination. PMID- 4040196 TI - Quality assurance in 1984. PMID- 4040197 TI - [Cogan's syndrome. Recovery from sudden hearing loss after prompt treatment with corticosteroids]. PMID- 4040198 TI - New technique for the argon laser in the treatment of port wine stains. PMID- 4040199 TI - Oxytocin reduces intravenous heroin self-administration in heroin-tolerant rats. AB - Intravenous self-administration of heroin was studied in experimentally naive rats, as compared to this behavior in animals rendered tolerant to heroin by multiple injections. The tolerant rats also exhibited mild signs of spontaneous and naloxone-precipitated heroin withdrawal. Self-administration behavior developed earlier in the tolerant rats. In heroin-naive rats, oxytocin treatment did not influence the acquisition of heroin self-administration behavior. In the tolerant rats, on the other hand, oxytocin decreased the acquisition of heroin self-administration. When maintenance of heroin self-administration was studied in the tolerant rats, graded doses of oxytocin (0.05, 0.5 and 5 micrograms s.c.) decreased heroin intake. This finding, which is in agreement with previous data indicating that oxytocin attenuates the development of tolerance to and dependence on narcotic analgesics, suggests that the neuropeptide reduced the reinforcing efficacy of heroin in the tolerant organism. PMID- 4040200 TI - Effect of pentobarbital dependence on adenylate cyclase activity and calmodulin levels in rat cerebral cortex. AB - The effect of calcium (Ca2+) on the adenylate cyclase activity and calmodulin level of cerebral cortex was determined in pentobarbital dependent rats and age matched controls. Female Sprague-Dawley rats were made dependent and maintained on pentobarbital by eating a mixture of pentobarbital and rat chow (350 mg pentobarbital/30 g chow). Ca2+ activated then inhibited the adenylate cyclase activity associated with a 20,000 X g particulate fraction from pentobarbital dependent and age matched control rats. The values for one-half maximal stimulation and inhibition by Ca2+ did not differ significantly in either cortical preparation. However, the ability of Ca2+ to activate adenylate cyclase from pentobarbital dependent animals was significantly decreased (p less than 0.05) when compared to control animals. Pentobarbital (10(-4) - 10(-3) added to particulate fractions from naive control rats did not alter the ability of Ca2+ to activate adenylate cyclase. The calmodulin levels in the particulate fraction from pentobarbital dependent animals (30.2 +/- 6.7 ng calmodulin/mg protein) did not differ significantly when compared to control (33.0 +/- 4.7 ng/mg). By contrast, the calmodulin levels (37.9 +/- 5.9 ng/mg) in the 20,000 X g supernatant from cortex of pentobarbital dependent animals was significantly greater than the level in the supernatant from control animals (28.6 +/- 2.6 ng/mg). The ability of forskolin, dopamine, GTP or forskolin plus GTP (all at a concentration of 100 microM) to activate adenylate cyclase was significantly decreased in particulate preparations from pentobarbital dependent animals. In summary, our data show that alterations in calmodulin levels and a decreased responsivity of adenylate cyclase occur in animals physically dependent on pentobarbital. PMID- 4040201 TI - Dopamine inhibition of anterior pituitary adenylate cyclase is mediated through the high-affinity state of the D2 receptor. AB - The diterpenoid forskolin stimulated adenylate cyclase activity (measured by conversion of [3H]-ATP to [3H]-cAMP) in anterior pituitary from male and female rats. Inhibition of stimulated adenylate cyclase activity by potent dopaminergic agonists was demonstrable only in female anterior pituitary. The inhibition of adenylate cyclase activity displayed a typically dopaminergic rank order of agonist potencies and could be completely reversed by a specific dopamine receptor antagonist. The IC50 values of dopamine agonist inhibition of adenylate cyclase activity correlated with equal molarity with the dissociation constant of the high-affinity dopamine agonist-detected receptor binding site and with the IC50 values for inhibition of prolactin secretion. These findings support the hypothesis that it is the high-affinity form of the D2 dopamine receptor in anterior pituitary which is responsible for mediating the dopaminergic function of attenuating adenylate cyclase activity. PMID- 4040203 TI - [Biotin transport in the yeast Trichosporon cutaneum]. AB - Biotin transport was studied in the yeast Trichosporon cutaneum and was shown to be the active transport with Km = 1.5 X 10(-7) M. The process depended on the pH and temperature whose optimal values were pH 6.8-7.2 and 35-40 degrees C. T. cutaneum biotin permease was highly specific for biotin and was inhibited by biotin analogs. Biotin uptake by the cells was inhibited by glucose. Excess biotin in the growth medium caused partial repression of its transport system in the yeast. Synthesis of biotin permease by T. cutaneum depended on the nature of a catabolite present in the growth medium. The rate of biotin transport was highest in the cells grown in the presence of ramnose or arabinose and lowest in the cells utilizing galactose, lactose or xylose. PMID- 4040202 TI - [Production of extracellular higher fatty acids by yeasts grown on hexadecanoic acid]. AB - Production of exocellular higher fatty acids by Candida yeasts was studied during their growth in a mineral medium with hexadecane. The qualitative and quantitative composition of exocellular higher fatty acids was investigated during cultivation of Candida lipolytica VCM Y 2378(695) under the conditions of different aeration (5 and 80% saturation of the medium with oxygen). Palmitic (C16:0), palmitooleic (C16:1), oleic (C18:1) and linoleic (C18:2) acids predominated among other higher fatty acids. The overall amount of fatty acids increased and the content of unsaturated fatty acids decreased when the yeast growth was limited with oxygen. PMID- 4040204 TI - [Variability of cultures of Pullularia pullulans with different ploidy levels]. AB - As the level of ploidy rises in Pullularia pullulans, this causes an increase in the frequency of spontaneous and UV-induced auxotrophic mutants as well as mutants with a modified respiration activity while the frequency of morphological mutants decreases. The latter can arise as a result of recessive and dominant mutations. A higher frequency of morphological mutants in the haploid may be result of recessive mutations. It is likely that the frequency of dominant mutations increases in cultures with a higher level of ploidy since, as the difference between the frequency of UV-induced mutants and the frequency of spontaneous morphological mutants increases. PMID- 4040205 TI - Cisplatin and cytarabine administered intrapleurally as treatment of malignant pleural effusions. AB - Eight patients with histologically-documented malignant pleural effusions received a total of ten courses of intrapleurally administered chemotherapy with cisplatin (100 mg/m2) and cytarabine (10(-2) M). Sodium thiosulfate was simultaneously administered intravenously to protect against cisplatin-induced nephrotoxicity. There was no local toxicity observed and the only significant systemic toxicity (bone marrow depression) developed in a patient with poor marrow reserve prior to the initiation of therapy. Six of seven evaluable patients exhibited major reductions (greater than 75%) in the size of their effusions lasting for 2 to 10 plus months (median: 4 months). We conclude that the intrapleural administration of this chemotherapy regimen results in objective and subjective improvement in patients with malignant pleural effusions with minimal local and systemic toxicity (except for cisplatin-induced emesis) and does not require chest tube drainage or prolonged hospitalization. PMID- 4040206 TI - [Biological cycle of Multiceps multiceps isolated from man in the larval stage]. PMID- 4040207 TI - [Search for ovicides among chemical industrial waste products]. PMID- 4040209 TI - Quality assurance under the Missouri PRO program. PMID- 4040208 TI - Diurnal rhythms in calcium and phosphate metabolism in rodents and their relations to lighting and feeding schedules. AB - Diurnal fluctuations in serum Ca, inorganic phosphorus, Mg, and alkaline phosphatase activity and their relations to lighting and feeding schedules were investigated in nocturnal rats and diurnal asiatic chipmunks. The following results were obtained: all parameters in the animals fed ad libitum and adapted to a regulated light-dark cycle (with light from 7.00 to 19.00 h) showed diurnal rhythms; under the same experimental condition, the patterns of the rhythms in the nocturnal rat and the diurnal asiatic chipmunk were nearly 180 degrees out of phase with each other; under the continuous lighting condition for more than 10 days, the diurnal rhythms of the parameters in rats decreased in their amplitudes, and phase shifts or marked modulations in the diurnal curves occurred when the time of availability of food was restricted from 9.00 to 17.00 h without altering the lighting schedule. The above findings support an idea that the rhythmicity is one of the essential features involved in the Ca metabolism. It is demonstrated that the environmental photofraction is one of the essential factors in generating or in maintaining the circadian rhythm of Ca metabolism as in other physiological processes and that the feeding time also could have a marked effect on the diurnal rhythm in the Ca metabolism. PMID- 4040210 TI - Multicentric angiosarcoma of the tarsal and metatarsal bones. A case report and literature review. PMID- 4040211 TI - [Acanthocytosis in chronic septic granulomatosis: the McLeod syndrome]. AB - Acanthocytosis was observed in a boy suffering from Chronic Granulomatous Disease (CGD). Further investigations revealed weak Kell-antigen-expression on the patient's erythrocytes. This so-called "McLeod-Syndrome" is due to the absence of Kx, the Kell antigen precursor substance. So far, 8 cases of an association between McLeod-Syndrome and CGD have been reported. Both genetic defects are closely linked on the X-chromosome and may therefore be inherited together. In female carriers, the variable inactivation of one X-chromosome according to the Lyon-hypothesis is the reason for the appearance of both normal and McLeod erythrocytes at the same time. This was observed in the mother and sister of our patient too. Blood transfusions should be avoided, because McLeod-patients are at risk to form antibodies against the precursor substance Kx common to the erythrocytes of virtually all people. These patients should therefore be encouraged to donate blood which can be stored frozen and used either as autotransfusion (for the patient himself) or for other McLeod-patients. PMID- 4040212 TI - Abnormal growth hormone and dwarfism. PMID- 4040213 TI - Paternal cyclophosphamide treatment of rats causes fetal loss and malformations without affecting male fertility. AB - The use of cytotoxic, mutagenic and carcinogenic agents as treatment for various types of cancer may be particularly hazardous in men of reproductive age as there exists the possibility that this may lead to congenital malformations in the progeny. Such agents can affect fertility and other aspects of male reproductive function, for example, treatment with anti-cancer drugs such as cyclophosphamide has been associated with oligozoospermia, azoospermia and increased levels of serum follicle-stimulating hormone (FSH). Depending on the cumulative dose and the duration of treatment, spermatogenesis often returns but this may take years. The relevance of the effects of such chemicals on the male reproductive system to the offspring is poorly understood. We have set out to determine whether present tests of male reproductive function (that is, endocrine status, numbers of spermatozoa, fertility) can predict deleterious effects of a paternally administered agent on the offspring. Here, we report that chronic administration in rats of low doses of the widely used drug cyclophosphamide had minimal effects on the male reproductive system and fertility, but resulted in malformations and retardation of growth in the surviving fetuses and a high frequency of fetal death. Thus, adverse effects on the fetus cannot be predicted from the effects of a drug on the male reproductive system. PMID- 4040214 TI - Human N-myc gene contributes to neoplastic transformation of mammalian cells in culture. AB - Proto-oncogenes represent a group of eukaryotic genes whose activated forms are implicated in the development of cancer. We have recently identified a human gene, N-myc, that is distantly related to the proto-oncogene c-myc. N-myc is expressed at abnormally high levels consequent to amplification in numerous human neuroblastoma cell lines and metastatic neuroblastoma tumours. In addition, enhanced expression of N-myc, often a result of amplification, has been found in retinoblastoma cell lines and tumours (refs 5, 7 and M.S., unpublished data) and in cell lines derived from small-cell carcinomas of the lung. Here, we show that enhanced expression of N-myc subsequent to co-transfections of an N-myc expression vector and the mutant c-Ha-ras-1(EJ) (from the human bladder carcinoma cell line EJ) is a factor in tumorigenic conversion of secondary rat embryo cells. The transformed cells elicit tumours in athymic mice and isogeneic rats. The ability of N-myc to contribute to neoplastic transformation of cultured mammalian cells raises the possibility that enhanced expression consequent to amplification of N-myc may be a factor in the aetiology of human neuroblastoma. PMID- 4040215 TI - Unexpected potentiation by discriminant benzamide derivatives of stereotyped behaviours elicited by dopamine agonists in mice. AB - Among four stereotyped manifestations that can be simultaneously quantified in mice treated with apomorphine (APO), two of them (climbing and sniffing) emerge at low APO dosages (below 1 mg/kg) whereas licking and sniffing require APO dosages above 6 mg/kg. However, in mice pretreated (either i.p. or i.c.v.) with sulpiride (especially the levo isomer) or (+/-)amisulpride in moderate dosage stereotyped licking and sniffing are elicited by APO in much lower dosage (0.75 mg/kg). As a consequence, in mice pretreated with these benzamide derivatives and receiving 0.75 mg/kg APO, a biphasic effect was observed: licking and gnawing progressively appear at low dosages, whereas they are progressively abolished at higher dosages. This potentiation of the effects of APO by (+/-) amisulpride is even more obvious (maximal scores increased) with larger test-doses of the dopamine agonist (up to 5 mg/kg). Amisulpride also allows the emergence of the two stereotyped behaviours in mice receiving other dopamine agonists in subthreshold dosages (Dipropyl 5,6-ADTN, dexamphetamine or cocaine). The potentiation of APO is still observed after dopamine depletion by reserpine and alpha-methylparatyrosine, whereas that of dexamphetamine is abolished. In contrast with the benzamide derivatives, haloperidol does not potentiate at any dosage the effect of APO but, at 0.15 mg/kg, suppresses licking and gnawing elicited by 0.75 mg/kg APO in mice pretreated with 6.25 mg/kg amisulpride or veralipride.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4040216 TI - Effects of discriminant and non-discriminant dopamine antagonists on in vivo accumulation of 3H-N-propyl-norapomorphine in mouse striatum and tuberculum olfactorium. AB - The in vivo accumulation of 3H-N-propyl norapomorphine in mouse striatum and tuberculum olfactorium and its inhibition by a series of classical neuroleptics and discriminant benzamide derivatives previously identified in behavioural and radioligand experiments has been studied. The ID50 values in the two brain areas did not significantly differ with any studied compound. In addition the regional distribution of a discriminant compound related to sulpiride and administered in tritiated form to rats was rather homogeneous. These data do not indicate a preferential accumulation of these compounds in limbic as opposed to striatal areas. PMID- 4040217 TI - Chlorimipramine, electroconvulsive shock and combination thereof: differential effects of chronic treatment on apomorphine-induced behaviours and on striatal and mesocortical dopamine turnover. AB - We studied the influence of different pretreatment regimens (Chlorimipramine-Cmi, electroconvulsive shock-ECS, and Cmi + ECS all regimens being applied for either 2 or 15 days) on the open field behaviour, on the striatal and on the prefrontal dopamine-PFC DA turnover in rats injected with either apomorphine-AP 25 micrograms/kg (stimulating presynaptic DA receptors), AP 200 micrograms/kg (stimulating post-synaptic DA receptors), or vehicle (control). In the controls, AP 25 micrograms/kg reduced the locomotor activity and the striatal, but not the PFC DA turnover. AP 200 micrograms/kg increased the locomotor activity and reduced the striatal but not the PFC DA turnover. Short-term pretreatment: ECS and Cmi + ECS prevented the decrease of striatal DA turnover after AP 25 micrograms/kg. No other influence of any pretreatment on behaviour or DA-turnover became significant. Long-term pretreatment: Chronic Cmi: marginally increased the open field behaviour and marginally decreased the PFC DA turnover; significantly increased the effect of AP (200 micrograms/kg) on striatal DA turnover and the effect of AP (25 and 200 micrograms/kg) on PFC DA turnover. Repeated ECS: decreased locomotion and rearing and increased PFC DA turnover; increased the effect of AP (200 micrograms/kg) on locomotion and on striatal DA turnover; decreased the effect of AP (25 and 200 micrograms/kg) on PFC DA turnover. Chronic Cmi + ECS: decreased locomotion and rearing and marginally decreased PFC DA turnover; increased the effect of AP on hyperlocomotion and on striatal DA turnover.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4040219 TI - [HCG must remain]. PMID- 4040218 TI - Attenuation of cisplatinum-induced nephrotoxicity in the rat by high salt diet, furosemide and acetazolamide. AB - The influence of variations in sodium chloride diet, furosemide and acetazolamide on nephrotoxicity induced by cisplatinum have been investigated in the rat by measuring serum creatinine concentrations 5 days after cisplatinum (5 mg/kg, ip) administration. Sodium chloride depletion enhanced, while sodium chloride loading minimized changes in renal function. Increases in urine flow rate following a dextrose water load failed to alter the nephrotoxic response. Both furosemide and acetazolamide, given 30 min before cisplatinum, attenuated the nephrotoxic response. In contrast, neither sodium chloride loading, furosemide, nor acetazolamide influenced the change in renal function when given 30 min after cisplatinum. These observations indicate that renal damage due to cisplatinum can be modified by alterations in dietary salt and by diuretics and that the extent of ultimate renal damage is dependent on factors occurring immediately after cisplatinum administration. PMID- 4040220 TI - Muscarinic receptors in the preoptic area are sensitive to 17 beta-estradiol during the critical period. AB - The relationship between the steroid hormone 17 beta-estradiol and the muscarinic cholinergic receptors present in the preoptic area (POA), median hypothalamus and posterior hypothalamus of female rats was examined in vitro at various stages of the estrous cycle. Muscarinic receptors varied in a cyclic manner, specifically in the POA, as shown by an increase in the proportion of high-affinity agonist binding sites (RH) to 60% during the proestrus, as compared to RH proportion observed during diestrus-2 and during the afternoon of proestrus (35%). Exposure of POA homogenates to 17 beta-estradiol resulted in conversion of RH to low affinity agonist binding sites (RL). This effect of the hormone was also restricted to the POA taken from rats during the morning of proestrus. It was blocked by the antiestrogenic drug, clomiphene, and could be prevented by preoccupation of the muscarinic receptors by their own ligands prior to the addition of hormone. It follows that significant changes in POA muscarinic receptors in situ exactly coincided with the known critical time period characterized by high estrogen levels and high levels of estrogen receptors in the POA. These changes in muscarinic receptors might thus conceivably reflect variations in cholinergic activity in the POA during the estrous cycle. PMID- 4040221 TI - Choline acetyltransferase activity in the pars distalis, preoptic area and striatum during the rat estrous cycle. AB - Choline acetyltransferase (CAT) activity of the striatum, preoptic area (POA), and pars distalis (PD) of the anterior pituitary gland was measured on each day of the 4-day estrous cycle of adult Wistar rats. Only in the PD did CAT activity vary significantly during the cycle, with the activity being lower during estrus than at other stages of the cycle. The CAT activity of the PD was extremely low, approximately 500 nmol/h/g protein, and, therefore, the specificity of the CAT activity of the PD was verified in studies on substrate requirement, the effect of a CAT inhibitor, and by paper chromatography of the reaction products. Measurement of CAT activity in saline-perfused glands, in sections of tissue taken from the lateral extremes of the PD and in hypophysial portal blood showed that the CAT activity of the PD was intrinsic, and not due to CAT activity in entrapped blood or adjacent tissues. The precise cellular origins of CAT in PD and the significance of the cyclical variation require further investigation. PMID- 4040222 TI - Circadian pattern of multiunit activity of the rat suprachiasmatic nucleus during the estrous cycle. AB - Multiunit activity (MUA) of the suprachiasmatic nucleus (SCN) of the hypothalamus and medial preoptic area (MPOA) was recorded in chronically implanted, freely moving female rats. The integrated MUA of the SCN and MPOA was significantly higher in the dark than in the light period of day. Superimposed upon this diurnal rhythmicity in the SCN were 3.0- to 3.5-hour ultradian oscillations of MUA, with the fluctuations showing the highest variability at night. A significant increase in SCN MUA consistently preceded the offset of light by 1 h, whereas during the dark-light transition a marked decrease of neuronal firing occurred after the onset of light. Analysis of MUA base level--recorded during slow wave sleep--revealed that the average activity in the SCN was lowest on the day of diestrus-II, began to increase on proestrus night, and reached the highest values during estrus. Bilateral transection of the optic nerve, 4-6 weeks prior to electrical recordings, abolished the estrous cycle and the circadian pattern of neuronal firing of the SCN. An ultradian oscillation of integrated MUA in blind rats occurred with the same average intervals (3.0-3.28 h) but the amplitude was much higher than in intact cycling rats. Data indicate that there are correlated changes in basal MUA levels of the SCN and the stages of the estrous cycle. Furthermore, they suggest that maintenance of hormonal cyclicity and circadian rhythm of neuronal function requires intact retinohypothalamic connections. PMID- 4040223 TI - Effect of Ca2+ on the binding characteristics of muscarinic receptors in rat adenohypophysis--variation during the estrous cycle. AB - The effect of Ca2+ on the biochemical characteristics of muscarinic receptors in the adenohypophysis of male and female rats at the various stages of the estrous cycle was investigated in binding experiments using the specific muscarinic antagonist N-methyl-4-piperidyl benzylate ( [3H]-4NMPB) and the muscarinic agonist oxotremorine. By using Ca2+ chelators such as EGTA, and Ca2+ channel blockers such as D-600, we showed that Ca2+ profoundly alters the binding characteristics of both antagonists and agonists to the muscarinic receptors. In female rats the effect of Ca2+ on antagonist binding is mainly on the maximal binding capacity of the receptors, while changes in the dissociation constants are much more moderate. The effect is expressed in the ability of Ca2+ to expose or to eliminate binding sites as a function of the estrous cycle. In agonist binding, the presence of Ca2+ has a pronounced effect on the proportion of high affinity binding sites, which parallels the changes induced in antagonist binding throughout the estrous cycle. Interestingly, the natural progression of the cycle from diestrus 2 to the estrous stage undergoes a change identical to that occurring in vitro upon Ca2+ removal. D-600 can completely block the effect of Ca2+ on the binding of both [3H]-4NMPB and oxotremorine. The concentration of D 600 required in order to induce such blocking is also dependent on the estrous cycle. It appears that the progression of the estrous cycle is accompanied by changes in the muscarinic receptors which may in turn be coupled to Ca2+ channels. PMID- 4040224 TI - Ovulatory function and retinal catecholamine concentrations in female rats with and without inherited retinal photoreceptor degeneration. AB - The timing of the critical period and LH surge during the afternoon of proestrus was unchanged in female rats with degenerated retinal photoreceptors (Hunter and Royal College of Surgeons strains), when compared to female rats with intact retinae (Piebald Virol Glaxo and Wistar strains). Both RCS and Wistar strains responded to constant light (LL) exposure by attaining persistent vaginal cornification at the same rate. In addition, both RCS and Wistar strains regained normal estrous cycles when moved from LL to control lighting (LD). Therefore, an intact retinal photoreceptor layer is not essential for normal ovulatory function. In addition, these results show that the effects of LL on gonadotrophin secretion are mediated through the brain and are not the result of retinal degeneration. Measurements of retinal concentrations of dopamine (DA) and its metabolite, 3,4-dihydroxyphenylacetic acid (Dopac), in Wistar and RCS rats showed that concentrations of both compounds were reduced by LL, and then increased back to control values when animals were moved back into LD. Although the magnitude of the changes in retinal concentrations of DA and Dopac was greater in Wistar than in RCS rats (possibly related to the degeneration which occurs in Wistar but not RCS rats), these results suggest that dopaminergic cells, probably within the amacrine cell population of the retina, respond to different light regimes, perhaps by changes in activity. PMID- 4040225 TI - [Echocardiographic study of myocardial masses in primary hypertrophic cardiomyopathy and in hypertensive cardiomyopathy]. PMID- 4040226 TI - [Use of the appendix in the reconstruction of ureteral continuity in an unusual clinical case of advanced-stage ovarian carcinoma]. PMID- 4040227 TI - Lesions of ventral tegmental dopamine neurons delay the development of tolerance to morphine catalepsy. AB - Selective lesions of the dopamine (DA) neurons of the ventral tegmental area (VTA) were found to substantially delay the development of tolerance to morphine induced catalepsy, in comparison with sham-operated controls receiving morphine. Lesioned subjects receiving vehicle injections showed no catalepsy. The data suggest that tolerance to morphine catalepsy requires intact VTA DA neurons. Furthermore, since the acute cataleptic response was intact in lesioned animals, the data suggest that the mechanisms involved in the cataleptic response to morphine are dissociable from those which bring about tolerance to that response. PMID- 4040228 TI - Synthesis of multiple peptides from a larger precursor in the neuroendocrine caudo-dorsal cells of Lymnaea stagnalis. AB - The biosynthesis, transport and release of multiple peptides by the egg-laying controlling neuroendocrine caudo-dorsal cells (CDCs) of Lymnaea stagnalis were studied. High-performance gel permeation chromatography was used to resolve newly synthesized peptides after pulse-chase experiments with radioactive amino acids. The ultimate precursor is a approximately 35 kd (K) peptide which is produced in the CDC somata. It gives rise to intermediate products (approximately 20 K, approximately 10 K and approximately 7 K) and a number of end products which include a approximately 4.5 K peptide (the ovulation hormone) and other peptides (approximately 6 K, approximately 3.5 K and approximately 2 K). The end products are transported in neurosecretory granules to the CDC axon terminals in the cerebral commissure where they are released into the medium during electrical discharges of the CDC system. PMID- 4040229 TI - Choriocarcinoma of the ovary. AB - Six cases of primary ovarian choriocarcinoma were reviewed. Five-year follow-up was available for all patients except the most recently diagnosed case. Overall survival was 80%. The problems of distinguishing between gestational and nongestational neoplasia and differentiating primary from metastatic disease are discussed. Surgical staging of disease may be more informative in initiating aggressive chemotherapy than in determining the gestational or nongestational origin of the tumor. PMID- 4040230 TI - [State of the optic disk and visual field boundaries examined daily by perimetry in patients in the early stages of glaucoma]. PMID- 4040231 TI - [Cyloscopy in uveitis]. PMID- 4040232 TI - [Establishment of the optimal space-time characteristics for trans-scleral laser irradiation and its experimental study]. PMID- 4040233 TI - Unresectable non-small cell lung cancer chemotherapy with high-dose cisplatin and etoposide. AB - 69 patients with unresectable non-small cell lung cancer, previously untreated, received cisplatin 100 mg/m2 on day 1 and etoposide 120 mg/m2 on days 4, 6, 8 at 4-week intervals. 66 patients were evaluable for tumor response and toxicity. Overall objective response was 25.7% (3 complete responses and 14 partial responses). Response rate in limited disease was 41% and in patients with performance score 0 it was 40%. Squamous cell carcinoma and adenocarcinoma responded in 31 and 24% of evaluable patients. Complete response was associated with a long duration of remission. Median survival time of responding patients was significantly superior to the median of nonresponding patients (p less than 0.001) but compared to stable disease no statistical significance was demonstrable (p greater than 0.05). Hematological and renal toxicity of proposed regimen was generally mild. Nausea and vomiting were the most noxious side effects. PMID- 4040234 TI - Effects of mild hearing loss on auditory processing. AB - The impact on language learning of mild hearing loss due to otitis media with effusion has forced a new look at the dynamics of central auditory processing. A model of auditory deprivation that would produce the test results that define CAP deficits would be a mild conductive hearing loss. It is relevant to reexamine CAP theory in terms of such hearing loss. PMID- 4040235 TI - Interactions of the cysticercoids of Hymenolepis diminuta and raillietina cesticillus in their intermediate host, Tribolium confusum. AB - This study was based on the experimental exposure of beetles to homologous and heterologous infections of Hymenolepis diminuta and Raillietina cesticillus. The results demonstrated that, for both species over the range of parasite densities employed, the presence of a primary infection had no effect on the establishment success of an homologous challenge infection. The establishment success of R. cesticillus cysticercoids was not affected by the presence of an H. diminuta infection. The existence of an R. cesticillus infection, however, severely reduced the establishment success of an H. diminuta infection. The reduction in H. diminuta establishment was greatest in R. cesticillus infections less than 10 days old. The plausibility of some of the mechanisms that are potentially responsible for the reduction in H. diminuta establishment success is discussed, as is the possible ecological significance of these results. PMID- 4040236 TI - Creatine kinase brain isoenzyme: relationship of cerebrospinal fluid concentration to the neurologic condition of newborns and cellular localization in the human brain. AB - Immunocytochemical study of human brain showed creatine kinase brain isoenzyme (CKBB) present in both neurons and astrocytes. Because creatine kinase brain isoenzyme is an intracellular enzyme that might be released with brain injury, its concentration in the CSF of newborns was measured using a radioimmunoassay. Infants who suffered a documented neurologic insult (a cerebroventricular hemorrhage or a CNS infection) were found to have a greater mean CSF creatine kinase brain isoenzyme concentration than those without a history of neurologic insult. Infants with a high concentration had a poor short-term outcome (death or neurologic abnormality when discharged) more frequently than did those with a lower concentration. Infants with a grade 3 or 4 cerebroventricular hemorrhage had a higher mean concentration than did those with a grade 1 or 2 hemorrhage. These data are consistent with the hypothesis that CSF creatine kinase brain isoenzyme is a metabolic indicator of brain damage in newborns. PMID- 4040237 TI - Acoustic reflectometry in the detection of middle ear effusion. AB - Acoustic reflectometry, a new technique for detecting middle ear effusion, was compared with results from tympanocentesis or myringotomy in 75 patients (141 ears). There was a highly significant association (P less than .0001) for ears having middle ear effusion with high reflectivity (5 through 9 units) and for ears having no middle ear effusion with low reflectivity (0 through 4 units). In a pediatric population with middle ear effusion present in 98 of 141 ears and using reflectivity readings greater than 4 to indicate middle ear effusion, the sensitivity of this technique was 86.7% and the specificity was 69.8%. False positive errors usually occurred in ears with thick tympanic membranes, or in ears in which reflectivity was determined prior to the induction of anesthesia. False-negative errors usually occurred in ears with both air and fluid. This technique was validated by direct comparison with tympanocentesis or myringotomy and can be used with pneumatic otoscopy and impedance tympanometry to follow children with middle ear effusion. PMID- 4040238 TI - Changes in the brain and core temperatures in relation to the various arousal states in rats in the light and dark periods of the day. AB - In rats, brain temperature (Tbr) and core temperature (Tc) were recorded in parallel with the sleep-wake activity throughout the 24-h diurnal cycle, consisting of a 12-h light (L) and a 12-h dark (D) period. In order to characterize the temperature changes associated with the arousal states in the L and the D separately, (i) the average temperatures in wakefulness (W), non-rapid eye movement sleep (NREMS) and REM sleep (REMS), and at the transitions between the arousal states were calculated; (ii) the courses of temperatures before and after the transitions (falling asleep, awakening from NREMS or REMS, transition from NREMS to REMS) were determined; (iii) the rates of changes in Tbr and Tc were calculated for each state; and (iv) the correlations between the temperatures and the overall length of each arousal state, and between Tbr and Tc were studied. In both the L and D periods, Tbr and Tc decreased at the beginning of NREMS, then levelled off, and increased slightly before awakening. Apart from short arousals which did not affect temperature, Tbr and Tc increased in W, peaked 15-20 min after awakening, and declined significantly before the falling asleep. In REMS, Tbr increased at a high rate, while a slight increase in Tc was evident in the L only. Correlations between the temperatures and the arousal states were found in both the L and the D. The courses of Tbr and Tc were also correlated. The results support the existence of characteristic changes in body temperature related to the arousal states in the rat. PMID- 4040239 TI - Friedreich's ataxia presenting as cardiac disease. AB - Three male children with Friedreich's ataxia, from a single family, are described. The first patient presented as a cardiologic problem with anginalike chest pain. He was found to have echocardiographic evidence of concentric left ventricular hypertrophy (LVH). He later developed ataxia. The younger brother also had LVH but was asymptomatic and later became ataxic. The elder brother was already ataxic at the time of diagnosis. To our knowledge this is the first report of echocardiographic concentric left ventricular hypertrophy preceding the neurologic syndrome of Friedreich's ataxia. PMID- 4040240 TI - New antimicrobial agents for pediatricians. PMID- 4040241 TI - [New therapeutic agents in idiopathic thrombopenic purpura]. PMID- 4040242 TI - [Acute thrombopenic purpura after the administration of Polopirin]. PMID- 4040243 TI - Benign diseases of the uterine cervix. Ruling out neoplasia a diagnostic priority. PMID- 4040244 TI - Effects of social policy on the heritability of educational achievement. PMID- 4040245 TI - Effects of psychotropic drugs on discrimination conditioning in olfactory bulbectomized rats. AB - In the acquisition process of discrimination avoidance conditioning, bilateral olfactory bulbectomized rats showed poor discrimination conditioning since both the avoidance responses to positive conditioned stimuli (CS) and the incorrect responses to negative CS increased. The effects of various psychotropic drugs upon this poor discrimination conditioning were examined. Chlordiazepoxide 5 mg/kg, IP, produced an increase in the avoidance responses with simultaneous decrease in the incorrect responses, thus making the discrimination possible. Chlorpromazine 2 mg/kg, IP, worsened the discrimination by decreasing both the avoidance and incorrect responses as compared with saline-treated rats. Amitriptyline 10 mg/kg, IP, decreased the incorrect responses without affecting the avoidance responses, thus making the discrimination possible. Methamphetamine 0.5 mg/kg, IP, increased both the avoidance and incorrect responses resulting in poor discrimination conditioning. From these results, it was found that the poor discrimination conditioning of O.B. rats was improved by psychotropic drugs like chlordiazepoxide and amitriptyline. PMID- 4040246 TI - Naltrexone antagonizes the biobehavioral adaptation to cold water stress in rats. AB - The reported studies on the development of tolerance to the analgesic effects of stress have been mostly concerned with the involvement of opioid or non-opioid substances in stress-induced analgesia (SIA). To further investigate the processes involved in SIA tolerance, rats were exposed to forced intermittent cold water swim (ICWS, 18 exposures, 3/min, 10 sec each) on 16 consecutive days. On days 15 and 16, they were injected prior to swim with saline and naltrexone (10 mg/kg), respectively. During swim, three types of readily identifiable behaviors were observed. They may be characterized by immobility and horizontal floating (Type I), intensive activity and escape attempts (Type II), and passivity and "behavioral despair" (Type III). In the acute condition, only Type II and Type III appear in sequence. In the chronic condition, the sequence of behaviors is: Type I, Type II, and Type III. Thirty minutes after swim, analgesia, core temperature, and degree of inactivity were measured. With chronic exposure, tolerance developed to the analgesia, core hypothermia and hypoactivity induced by the ICWS. Type I behavior appeared on day 3 or 4 and persisted throughout the chronic treatment. Type II behavior did not adapt. Naltrexone (10 mg/kg) antagonized the adaptive aspect of all those variables where adaptation or tolerance were found (analgesia, hypoactivity, core hypothermia, and Type I behavior) but had no effect on Type II behavior where no adaptation was observed. It is suggested that the endorphins have a functional role in the behavioral and and physiological adaptation to aversive stressful environmental situations. PMID- 4040247 TI - Evidence for the involvement of histamine in the regulation of blood-brain barrier permeability. AB - Role of histaminergic mechanisms in the regulation of blood-brain barrier (BBB) was assessed in dog. Histamine increased the entry of sodium fluorescein from the blood to the cerebrospinal fluid (CSF) in a dose-dependent manner. Histamine receptor antagonists, mepyramine (H1) and metiamide (H2) per se did not affect the entry of dye in the CSF. Mepyramine failed to affect the change induced by histamine whereas metiamide completely blocked the histamine-induced entry of sodium fluorescein in CSF. 2-Methyl histamine, a specific H1-agonist, did not affect the barrier permeability. However, 4-methyl histamine, a specific H2 receptor agonist significantly increased the permeability of BBB. This increase was blocked by metiamide. Forskolin, a stimulant of adenylate cyclase, also increased the entry of dye in the CSF which could be significantly blocked by metiamide. It is concluded that histamine increases the permeability of BBB by affecting H2-receptors linked to adenylate cyclase. PMID- 4040248 TI - Gastric secretion and mucosal lesions in morphine-dependent rats. AB - The gastric mucosa and basal gastric secretion of morphine-dependent rats with pyloric occlusion were examined. Morphine tolerance and dependence were induced by administering increasing concentrations of morphine sulphate in the drinking water for 3 weeks, and were confirmed by a decreased analgesic response to morphine in the tail-immersion test and by occurrence of a naloxone-precipitated withdrawal syndrome, respectively. It was found that although the basal gastric secretion of morphine-dependent rats was not significantly different from that of naive animals, the former group showed a significantly higher gastric glandular mucosal ulcer index. Intraperitoneal injection of naloxone induced significant withdrawal effects but did not produce significant changes in gastric secretion or in ulcer index. PMID- 4040249 TI - Optimal laser parameters for port wine stain therapy: a theoretical approach. AB - The optimal parameters for laser therapy of port wine stains (PWS) have been deduced from temperature calculations on two models: (i) the four-layer model; and (ii) the tube model in which two plane parallel layers, representing the epidermis and dermis, and a dermal rectangular blood vessel are considered. The calculations were performed with a vessel of average cross section 0.06 mm X 0.08 mm located in the centre of the laser beam. The numerical calculations were performed by an alternate direction-implicit finite difference method. The optimal parameters were: wavelengths lambda = 415, 577 and 540 nm; pulse time, 1 ms less than t1 less than or equal to 10 ms; and beam radius W1 greater than 0.1 mm. The energy densities E1 (for t1 = 1 ms) required to coagulate blood vessels down to a depth of 0.65 mm in order to establish bleaching of the PWS were 0.5, 1.6 and 2 J cm-2 for the different lambda respectively. The value for the argon laser (lambda = 488 and 514.5 nm) was E1 = 6.5 J cm-2 (t1 = 1 ms). Because, for this pulse time, heat summation effects at the boundary of the laser beam cause no drastic increase in local temperature at optimal wavelengths, the stripe technique was again considered and compared with the separated spot technique. The Nd-YAG and CO2 lasers prove even less selective than the argon laser. The influence of cooling the skin with water shows that only for lambda = 577 nm and t1 = 0.1 s is there an increase in E1 from 2.5 to 6 J cm-2 for which dermal damage occurs. PMID- 4040250 TI - Control of the temporal location of schedule-induced attack in pigeons. AB - Pigeons were exposed to complex fixed-ratio schedules to assess whether the temporal location of schedule-induced attack was controlled by the discriminative properties of food or by the aversive aftereffects of food withdrawal. When exposed to a multiple fixed-ratio 25 fixed-ratio N schedule in which either fixed ratio component occurred with equal probability according to a quasi-random sequence and in which the value of N ranged from 115 to 150 across subjects, all pigeons exhibited post-food attack against a rear-projected conspecific target predominantly at the signalled onset of the higher-valued ratio component. Exposure of subjects to a mixed fixed-ratio 25 chained fixed-ratio 25 fixed-ratio N-25 schedule, however, resulted in a shift of attack to the signalled onset of the fixed-ratio N-25 component rather than following food. A chained fixed-ratio 25 fixed-ratio N-25 schedule induced attack predominantly after food delivery rather than at the onset of the fixed-ratio N-25 component. These findings show that the temporal locus of schedule-induced attack is primarily controlled by a stimulus, whether food delivery or key color change, that reliably precedes a relatively long period of reinforcer unavailability. PMID- 4040251 TI - Effects of neonatal castration and testosterone treatment on sexual partner preference in the ferret. AB - Groups of male and female ferrets were tested in a T maze to determine whether they preferred to approach and interact with a sexually active male or an estrous female. Control male and female ferrets gonadectomized (GX) on postnatal Day 35 and tested in adulthood while receiving no hormone or testosterone (T) displayed no significant preference. When given estradiol benzoate (EB), however, control males preferred stimulus females whereas control females preferred stimulus males. When tested in adulthood with EB treatment, males GX on postnatal Day 5 showed a significant reduction in their approach to stimulus females, although they did not switch their preference to stimulus males and thereby resemble control females. Female ferrets GX on postnatal Day 5 and given a high dosage of T over postnatal Days 5-20 showed a significant reduction in their approach to stimulus males, although they did not switch their preference to stimulus females, and thereby resemble control males. The results suggest that extended perinatal exposure of male ferrets to T is required for the development of a sociosexual preference for females. PMID- 4040252 TI - Plasma prolactin levels during conditioned avoidance behavior in rats. AB - In these experiments, we examined the prolactin (PRL) response during the acquisition of a conditioned avoidance response (CAR). Rats were tested daily in a two-way shuttle box. They were presented with a light stimulation followed by an electric footshock. During each trial period, the rats were given the opportunity to escape the footshock by moving to a safe side of the box. Movement to the appropriate location after the warning signal (light) begins, but before the onset of the footshock, constitutes a CAR. Blood samples were collected from an indwelling cannula and analyzed by radioimmunoassay. PRL levels increased during early acquisition testing, when the rats had not learned to avoid the shock. After one week of testing, acquisition performance increased considerably (70% CARs) while PRL levels remained unchanged. Thus, we were able to show that as rats learned to modify their behavior in response to a stressful situation, they could also modify their PRL response to the stressor. PMID- 4040254 TI - Prolonged responsiveness to the maternal pheromone in the postweanling rat. AB - When rat young reach 27 days of age they stop responding to a pheromone carried in the feces of the lactating female. Because the consumption of such feces promotes the deposition of brain myelin, we suggested that response to the pheromone might continue as long as the amount of myelin per gram brain remained below adult levels. Our data support the suggestion. Pups deficient in myelin responded to the pheromone after 27 days of age. PMID- 4040253 TI - Postnatal lead exposure and the cholinergic system. AB - Previous reports have suggested that the behavioral effects of early lead (Pb) exposure may be due to an underlying deficiency in cholinergic function. To further examine this possibility, Long-Evans hooded rat pups were exposed to Pb for the first 25 postnatal days via the maternal milk. Dams were fed either 4.0% PbCO3 (High Pb), 0.4% PbCO3 (low Pb) or a Na2CO3 control diet throughout this period. Beginning at 65 days of age, animals were tested on behavioral tasks sensitive to both Pb exposure and cholinergic deficiency. Exposure to both levels of Pb impaired passive avoidance acquisition and produced lower rates of spontaneous alternation. Pb, however, had no clear effects on open field activity. The cholinergic agonist physostigmine (0.05 and 0.075 mg/kg) did not affect the behavior of control animals on any task, but in both Pb exposed groups physostigmine improved passive avoidance acquisition, increased the rate of spontaneous alternation and lowered open field activity scores. The cholinergic antagonist scopolamine (0.4 mg/kg) impaired passive avoidance acquisition, lowered the rate of spontaneous alternation and increased open field activity scores in control animals. Consistent with behavior characteristic of an inverted U shaped response curve, scopolamine (0.2 and 0.4 mg/kg) improved passive avoidance acquisition in both Pb exposed groups and decreased open field activity scores in the High Pb group. In all cases, the behavioral response of the Pb exposed animals may be interpreted as responses characteristic of cholinergically deficient animals. These results thus provide further evidence for cholinergic system involvement in the behavioral changes observed following early exposure to Pb. PMID- 4040255 TI - Maternal licking by virgin and lactating rats: water transfer from pups. AB - Rat dams provide water to their young via milk. Dams reclaim much of this water by licking the pups' anogenital areas, stimulating reflexive urination and consuming the pups' urine. Sensitized virgin rats, induced to act maternally do not provide water to pups, but they nevertheless lick them. To determine whether bidirectional transfer of water between the rat mother and her litter mediates maternal licking, water transfer from pups to sensitized virgins was compared with that to lactating dams. We used time-lapse video recordings to measure anogenital licking of pups. Sensitized virgins and lactating dams spent equivalent amounts of time licking the anogenital regions of test litters. We quantified the amount of water transferred from offspring to both virgins and dams by injecting pups with tritiated water and measuring the radioactive label in maternal plasma after interaction with a litter of 5-day-olds. Dams obtained more than twice as much urine from the litter in 4 hr than did the maternal virgins. Differences in the amount of water obtained from pups were due to differences in urine availability caused by the receipt of milk from the dams. When the dams' nipples were ligated, so that their pups received no milk, ligated dams and virgins consumed equivalent amounts of pup urine. Maternal licking and urine consumption are not dependent solely upon the bidirectional exchange of water between the dam and her offspring. PMID- 4040257 TI - Mouse killing, insect predation, and conspecific attack by rats with differing prior aggressive experience. AB - Mouse-killing, cockroach predation, and conspecific attack were examined in male Long-Evans rats with a history of intraspecific aggression (n = 20), defeat (n = 20), or no aggressive experience (n = 20). Roaches were more likely to be attacked during 30 min tests, and were attacked more rapidly than mice or rats regardless of previous social experience of subjects. Rats with aggressive experience attacked conspecifics more readily than subjects with defeat or no experience. There was no effect of prior experience on mouse-killing. These results indicate that mouse-killing does not correspond closely to either predation or intraspecific attack. PMID- 4040256 TI - Self-selection of dietary casein and soy-protein by the cat. AB - Growing specific-pathogen-free kittens were fed for two weeks a choice between two complete diets differing only in protein content. When casein diets containing 18, 36 and 54% protein were offered in the three possible combinations, the kittens consistently avoided the higher casein diets and kittens offered the two highest levels of casein significantly reduced their total food intake. In one soy-protein choice study, 16, 31 and 63% protein diets were each offered with a protein-free (PF) diet. When diets were similar in physical consistency, kittens selected similar amounts of both diets with the result that the PF:16% group consumed below their requirement of protein. In another soy-protein experiment the 16, 31 and 63% protein diets were offered in their three possible combinations. Kittens in all three groups selected similar amounts of both diets. Except for their avoidance of casein, the kittens did not regulate in a consistent manner their intake of protein and therefore, behaved very differently from the rat in the self-selection of dietary protein. PMID- 4040258 TI - The effects of vincristine on milk secretion and milk composition in the goat. AB - The effects of intramammary injection of vincristine on milk secretion were studied in goats. Vincristine inhibited milk secretion in a dose-dependent manner, with 1 mg decreasing milk yield to approximately 40% of previous yield. The inhibition was reversible with a full recovery of milk yield within a few days. During inhibition, there were significant changes in milk composition; Na concentration increased and K and lactose concentrations decreased, while Cl concentration was unaffected. Fat, protein, citrate and Ca concentrations all increased, particularly as milk yield was recovering. The concentrations in milk of the two lactose precursors, glucose and UDP-galactose, both increased. During inhibition and recovery, the secretion rates of three major components of milk, lactose, protein and fat, were affected to a different degree, with lactose secretion being inhibited to the greatest extent. The results are discussed in relation to the action of vincristine on milk secretion. It is proposed that vincristine's actions include a specific inhibition of lactose synthesis. PMID- 4040259 TI - [Radiologic diagnosis of hemangioblastoma]. PMID- 4040260 TI - Sow (Sus scrofa) follicular fluid: prostaglandin content and effect on the motility of isolated oviducts. AB - The present study provides information regarding the effects of the sow follicular fluid (FF) on the motility of isolated segments of swine and rabbit oviducts. In addition, the concentration of prostaglandins (PGs) F2 alpha, E2 and E1 in the follicular fluid of sow ovaries isolated at different stages of the sex cycle as well as the generation of the same PGs by walls of ovarian follicles in early and late proestrus, in estrus, in metestrus and in diestrus, were explored. The stimulatory contractile effect of proestrous FF in isolated segments of sow fimbria was antagonized by polyphloretin phosphate (PPP), a PG receptor blocker and by indomethacin, an inhibitor of PG synthesis. The positive inotropism evoked by the FF was mimiked by bradykinin and the influences of both interventions were similarly antagonized by PPP. It appears plausible that the inotropic effect of the preovulatory FF on the sow fimbria could be not only by PGs already present in the fluid, but also by the stimulation of the synthesis of tubal PGs by follicular fluid bradykinin. The FF also stimulated the ampullary tubal segments isolated from proestrous sows whereas the same volume of FF depressed significantly the isometric developed tension of rabbit ampulla. The total concentration of the three PGs in the FF from late proestrous follicles was significantly greater than that of the same PGs in the other two stages of the sex cycle (early proestrus and diestrus), whereas the concentration of each PG (PGE2, PGF2 alpha or PGE1), did not differ within any of the stages of the cycle. Furthermore, the total amount of the three PGs produced by the walls of follicles from late proestrous ovaries was also significantly greater than that generated by ovarian follicles from early proestrus, estrus, metestrus and diestrus. In summary the results document that the concentration of each one of the PGs measured (E2, E1 or F2 alpha) attained maximal values at the time of ovulation. The results regarding the effects of FF on the inotropic activity of fimbrial and ampullary segments of sow oviducts also suggest that the fluid might play a physiological role, favouring the capture and transfer of ova into the oviducts at the moment of ovulation. PMID- 4040261 TI - [Combination of nifedipine and diltiazem in refractory coronary spasm. Evaluation by provocation tests]. PMID- 4040262 TI - [Importance of Doppler echocardiography in the assessment of heart defects]. AB - Doppler ultrasound is now an established noninvasive method in cardiology. The most important indications are: 1. stenosis/insufficiencies of atrioventricular/semilunar valves, 2. dysfunction of artificial valves, 3. atrial and ventricular septal defects. The information obtained from Doppler ultrasound lends itself to quantitative or qualitative analysis. There is general consensus about the qualitative interpretation of Doppler ultrasound data, whereas quantitative analysis is still debated. A critical analysis of Doppler ultrasound data is a conditio sine qua non for correct interpretation. PMID- 4040263 TI - Ruptured vasa praevia. PMID- 4040264 TI - Phase I trials of high-dose cytosine arabinoside (HDara-C) and HDara-C plus cisplatin in patients with advanced malignancies. PMID- 4040265 TI - Cytarabine-cis-platin interactions in patients with advanced cancer. PMID- 4040266 TI - [Overdiagnosis of botulism]. PMID- 4040267 TI - Bernard-Soulier syndrome in two Afrikaner families. AB - The hereditary autosomal recessive disorder of platelet function known as the Bernard-Soulier syndrome (B-SS) is described in two Afrikaner families. Consanguinity exists in one of the families, which is descended from Trekboer Afrikaners who migrated from Rustenburg, Transvaal, to Angola in 1876 and then to SWA/Namibia in the 1920s. Since both families have French Huguenot ancestors and since there are 7 confirmed and 5 reported cases of B-SS in these two families, founder effect may be operating and causing this rare disorder to occur more frequently in this population group than would otherwise be expected. PMID- 4040268 TI - Intraoperative direct portography to achieve selective distal splenorenal shunt. AB - Repeated direct portography was performed during distal splenorenal shunt in 13 consecutive patients with esophageal varices due to cirrhosis of the liver. The roentgenogram taken at the completion of all operative procedures demonstrated incomplete disconnection between the mesentericoportal and gastrosplenic compartments in four patients. After further disconnection of the veins, the third portogram showed a successful isolation of both systems. The flow state through and the size of the shunt were appropriate in all instances on the roentgenograms. The shunt was patent in all patients, which was confirmed before discharge from the hospital. Hepatic encephalopathy was encountered one year after operation in one patient with the poorest hepatic functions. Esophageal varices disappeared or nearly disappeared at the time of discharge in ten patients. The remaining varices at discharge in another three patients completely disappeared within six months after operation. None of the patients experienced variceal bleeding during the follow-up period of three to 25 months. The results may indicate that repeated intraoperative direct portography is useful in achieving a selective distal splenorenal shunt. PMID- 4040269 TI - Successful total extirpation of hemangioblastoma originating in the medulla oblongata. AB - Hemangioblastomas of the medulla oblongata were successfully excised in two separate cases. The uncertainties of this procedure involve the value of preoperative radiation therapy, the relationship between the tumor and the medulla oblongata, and the surgical techniques themselves. Cardiovascular and respiratory disorders often complicate this type of surgery, and postoperative dysphagia is a frequent sequela. PMID- 4040270 TI - Intracerebellar hemorrhage due to cerebellar hemangioblastoma. AB - A rare case of a bleeding from a cerebellar hemangioblastoma is described. The tumor was diagnosed preoperatively with a computed tomography scan and a vertebral angiogram. The characteristic computed tomography scan findings and probable mechanism of bleeding are discussed. PMID- 4040271 TI - Protective effect of prostaglandin E1 on ischemia-induced acute renal failure in dogs. AB - The protective effect of intravenous administration of exogenous prostaglandin E1 on ischemia-induced acute renal failure was investigated in dogs. The parameters studied were renal cortical blood flow, renal function, survival time, and histologic changes. The model was prepared by clamping the renal artery for 1 or 2 hours. Renal cortical blood flow was measured by the hydrogen washout technique. After prostaglandin E1 administration, renal cortical blood flow increased significantly and renal function was maintained at relatively high levels with low serum creatinine and moderate creatinine clearance levels. Mean survival time increased markedly from 4.1 to 35.2 days by administration of prostaglandin E1. Ischemia-induced acute renal failure is usually accompanied by zonal necrosis of renal tubules prominent in the cortex. However, occurrence of these histologic damages could be virtually prevented by prostaglandin E1 administration (i.e., only minimal tubular necrosis was found in a small area of the cortex). We conclude from this study that postischemic administration of exogenous prostaglandin E1 does provide a certain degree of protection for the kidney, which may have a great clinical implication in improving the success rate of kidney transplantation, especially of cadaver donor kidneys. PMID- 4040272 TI - [Syndrome of high-altitude hypertrophic cardiomyopathy]. AB - The authors report the clinical, ECG, PCG and echocardiography data obtained in mountaineers suffering from associated essential hypertension and high-altitude pulmonary hypertension. Demonstrate the advisability of distinguishing the high altitude hypertrophic cardiomyopathy syndrome (HHCS) in part of mountaineers with essential hypertension living permanently at an altitude of 3600-4200 m over the sea level. The HHCS is marked by a lot of the clinical and echocardiographic signs which are regarded as characteristic of hypertrophic cardiomyopathy, particularly by appreciable asymmetrical hypertrophy of the interventricular septum. Criteria for the differential diagnosis between the HHCS and idiopathic hypertrophic subaortic stenosis are suggested. The possible mechanisms by which the HHCS develops in part of mountaineers are discussed. PMID- 4040273 TI - [Disorders of heart rhythm and conduction in dilated and hypertrophic cardiomyopathies]. AB - Idiopathic cardiomyopathies are characterized by diversity of clinical manifestations, among which heart rhythm abnormalities are the most common. The authors carried out qualitative and quantitative evaluations of heart rhythm abnormalities in patients with dilated and hypertrophic cardiomyopathies (DCMP, HCMP) and compared those abnormalities according to the data of daily ECG monitoring. Forty patients with DCMP and 30 with HCMP were examined. In 8 (25%) patients with DCMP and in 2 (6.7%) with HCMP, permanent atrial fibrillation was recorded. Among patients with sinus rhythm, supraventricular premature heart beats were found in 30 (96.8%) patients with DCMP and in 24 (85.7%) with HCMP. However, their number during 24 h exceeded 500 in 9 (29%) and in 7 (25%) patients, respectively. Supraventricular paroxysmal tachycardia (greater than or equal to 3 complexes at HR greater than or equal to 100/min) was recorded in 7 (22.6%) patients with DCMP and in 4 (14.3%) patients with HCMP. Ventricular premature heart beats were recorded in 38 (95%) patients with DCMP and in 21 (70%) patients with HCMP, polytopic in 31 (77.5% and 17 (56.7%), coupled in 227 (67.5%) and 10 (33.3%), ventricular paroxysmal tachycardia (greater than or equal to 3 complexes at HR greater than or equal to 100/min) in 22 (55%) and 5 (16.7%) patients, respectively. AV conduction abnormalities among patients with sinus rhythm were noted in DCMP and HCMP, in 12 (38.7%) and 1 (3.6%) cases, respectively. Thus, heart rhythm abnormalities are often encountered in both patients with DCMP and HCMP. However, in patients with DCMP, heart arrhythmias are graver and prognostically unfavourable.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4040274 TI - [Significance of ultrasonic segmental scanning in the diagnosis of rare heart pathology]. PMID- 4040275 TI - Thyroxine-induced differential mortality of cleft lip mouse embryos: dose- and time-response studies of the A/WySn strain. AB - Pregnant A/WySn mice, 20 to 30% of whose offspring have spontaneous cleft lip, were treated with thyroxine. Following treatment, cleft lip and normal embryos died, but cleft lip embryos died at a higher rate. The increased liability of cleft lip embryos to thyroxine-induced death was considered as a possible experimental route to identify the basic genetic defect that causes cleft lip. A time-response study indicated that cleft lip embryos responded more than normals following treatment on any of days 7 to 12 of gestation, that there is no sharply defined critical period, and that normal and cleft lip embryos do not differ in time of maximum sensitivity. A dose-response study showed linear responses of normal and cleft lip embryos on a probit-log dose scale, with a common slope and LD50's of 1.9 and 1.3 mg respectively. These dose-response properties indicate that normal and cleft lip embryos are probably killed by the same mechanism, but differ in dosage tolerance. That is, they differ quantitatively, not qualitatively. Thyroxine did not significantly change the cleft lip frequency, and the difference between normal and cleft lip embryos that leads to cleft lip itself is therefore not in the same pathway as that which leads to thyroxine induced death. A hypothetical example of the defect basic to both pathways is presented. PMID- 4040276 TI - Fetus-in-fetu: report of a case. AB - A 5 month-old female was brought to our clinic because of diarrhea and abdominal distension. A plain radiograph demonstrated a mass with a vertebral column in the right upper quadrant of the abdomen. At operation a mass was found to be retroperitoneal, well encapsulated, and connected to the abdominal aorta of the host by two small vessels; no other connections and adhesions were seen between the mass and the host. The ovaries, uterus, and other pelvic and abdominal viscera of the host were normal. The mass was diagnosed as a fetus-in-fetu. The fetus-in-fetu, encapsulated with an amniotic capsule, was covered with skin and had a top with long hair, two protuberances, an amniotic hernial sac, upper limbs with syndactylic fingers, a gluteal region, and lower limbs with polysyndactylic toes. A brain mass and a spinal cord were identified in the cranial cavity and the vertebral canal. Several spinal ganglia and a nerve plexus were found. A noselike structure, upper lip, maxillalike bone with teeth, tonguelike structure, intestines, ribs, bones of the extremities, and skeletal muscles were also identified. A cloacalike cyst was observed to have an opening in the external female genitalia. Microscopically, a small number of motor neurons were seen in the brain mass and the anterior horn of the spinal cord. In the spinal ganglia, ganglion cells were differentiated. The submucosal and myenteric plexuses were seen in the intestinal wall. Well-differentiated muscle fibers were often accompanied with myelinated nerve fibers. Hematopoiesis was observed in the cranial bone marrow. The presence of the sex chromatin was confirmed in the nuclei of motor neurons and polymorphonuclear leukocytes. Thus, the present fetus in-fetu, which was connected to the abdominal aorta of the host by two vessels, was a monozygotic twin which developed within its own amniotic cavity. PMID- 4040277 TI - Sudden cardiac death in adolescents. PMID- 4040278 TI - Release of tissue-type plasminogen activator by platelet-activating factor. PMID- 4040280 TI - Effect of Na+, K+ ion concentration on the production of plasminogen activator from a melanoma cell line. PMID- 4040281 TI - [Progesterone determination in milk]. AB - Samples of milk were taken every sixty minutes in ten cows for a period of ten hours to determine the concentrations of progesterone. The concentrations recorded were related to those in the strippings. All these samples furnished adequately reliable evidence of the presence of an active corpus luteum, with the possible exception of those taken during the last hours prior to milking in some cases. PMID- 4040279 TI - Urokinase-type plasminogen activator in ascites obtained from the patient with mammary cancer. AB - Plasminogen activator (ascites PA) was purified from the ascites of the patient with breast cancer using lysine-Sepharose, salting out, DEAE Sephadex A-50 and anti-urokinase (UK) Sepharose chromatography. The ascites PA was adsorbed on anti UK Sepharose and its activity was neutralized by anti-UK IgG fraction. The molecular weights of the ascites PA proteins were 70,000, 32,000 and 25,000 daltons. The ascites PA activated plasminogen and showed amidolytic activity for S-2444. Zymograms of ascites PA showed that 70,000 and 32,000 daltons proteins had a PA activity. The ascites PA thus contained two types of PAs, one was similar to LMW-UK and the other was an UK type tissue PA. PMID- 4040282 TI - Sclerotin and lipid in the waterproofing of the insect cuticle. AB - In all the cuticles studied waterproofing is effected by extracuticular material, a mixture of sclerotin precursors and lipids, exuded from the tubular filaments of the pore canals. In Rhodnius larval abdomen it is a layer of thickness similar to the outer epicuticle, believed to be composed of 'sclerotin' and wax, in Schistocerca larval sternal cuticle and in Carausius sternal cuticle it is similar. In Tenebrio adult sternal cuticle of the abdomen, in both the extracuticular exudation and the contents of the distal endings of the tubular filaments, the wax component is obscured by hard 'sclerotin'. In Manduca larva a very thin layer of 'sclerotin' and wax is covered by an irregular wax layer, average 0.75 micron, twice the thickness of the inner epicuticle. In Periplaneta and Blattella the abdominal cuticle is covered by a soft waxy layer, often about 1 micron thick, which is mixed with argentaffin material. Below this is a very thin waterproof layer of wax and 'sclerotin' continuous with the contents of the tubular filaments, which is readily removed by adsorptive dusts. In Apis adult abdominal terga free wax plus sclerotin precursors form a thin layer which is known to be removed by adsorptive dusts. In Calliphora larva there is a very thin layer of the usual mixed wax and sclerotin and below this a thick (0.5 micron) layer, lipid staining and strongly osmiophil, likewise extracuticular and exuded from the epicuticular channels. This material (which is often called 'outer epicuticle') has the same staining and resistance properties as the true outer epicuticle on which it rests. In the abdomen of Calliphora adult the waterproofing wax-sclerotin mixture forms a thin layer over the entire cuticle including the surface of the microtrichia. There is also a thin detachable layer of free wax on the surface. PMID- 4040283 TI - The transfer of lipid in insects from the epidermal cells to the cuticle. AB - The structure of the pore canals and the tubular filaments they contain are described in a series of insects and types of cuticle. In all these cuticles the tubular filaments arise from the plasma membrane of the epidermal cells and they contain argentaffin material, regarded as sclerotin precursors, and lipid staining material, regarded as wax precursors. These materials are transferred to the inner epicuticle and are exuded over the surface of the outer epicuticle to form the waterproofing layer as described in the preceding paper. They are also transported to those parts of the endocuticle destined to form hard exocuticle. There are no terminations of tubular filaments in the soft cuticle of Manduca larva, in the soft expanding cuticle of Rhodnius, and in the non-sclerotized post ecdysial endocuticle of Tenebrio. Apis. etc. In the puparium of Calliphora lipid appears to be added by the epidermal cells directly and not by way of tubular filaments. It is confirmed that lipid is a component of sclerotized cuticle. PMID- 4040284 TI - A model for de novo synthesis and assembly of tight intercellular junctions. Ultrastructural correlates and experimental verification of the model revealed by freeze-fracture. AB - The structure and function of intercellular tight (occluding) junctions, which constitute the anatomical basis for highly regulated interfaces between tissue compartments such as the blood-testis and blood-brain barriers, are well known. Details of the synthesis and assembly of tight junctions, however, have been difficult to determine primarily because no model for study of these processes has been recognized. Primary cultures of brain capillary endothelial cells are proposed as a model in which events of the synthesis and assembly of tight junctions can be examined by monitoring morphological features of each step in freeze-fracture replicas of the endothelial cell plasma membrane. Examination of replicas of non-confluent monolayers of endothelial cells reveals the following intramembrane structures proposed as 'markers' for the sequential events of synthesis and assembly of zonulae occludentes: development of surface contours consisting of elongate terraces and furrows (valleys) orientated parallel to the axis of cytoplasmic extensions of spreading endothelial cells, appearance of small circular PF face depressions (or volcano-like protrusions on the EF face) that represent cytoplasmic vesicle-plasma membrane fusion sites, which are positioned in linear arrays along the contour furrows, appearance of 13-15 nm intramembrane particles at the perimeter of the vesicle fusion sites, and alignment of these intramembrane particles into the long, parallel, anastomosed strands characteristic of mature tight junctions. These structural features of brain endothelial cells in monolayer culture constitute the morphological expression of: reshaping the cell surface to align future junction-containing regions with those of adjacent cells, delivery and insertion of newly synthesized junctional intramembrane particles into regions of the plasma membrane where tight junctions will form, and aggregation and alignment of tight junction intramembrane particles into the complex interconnected strands of mature zonulae occludentes. The distribution of filipin-sterol complex-free regions on the PF intramembrane fracture face of junction-forming endothelial plasmalemmae corresponds precisely to the furrows, aligned vesicle fusion sites and anastomosed strands of tight junctional elements.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 4040285 TI - [Lugol's solution and thyroid gland activity in cattle. Determination of the total thyroxine in blood plasma as a method for evaluating thyroid gland activity]. AB - The aim of the present investigations was to examine if an intrauterine treatment with Lugol's solution in cows influences the activity of the thyroid gland. The thyrotropin-stimulation test was used to evaluate the function of the thyroid gland. An injection of 10 I. U. thyreotropin induced within 3 hours an increase of the T4 blood concentrations which reached maximal values 9 hours after the treatment and thereafter decreased again. Thyreotropin concentrations increasing from 5 to 30 I. U. led to a dose-dependent increase of the T4 blood concentrations. The T4 values obtained by 40 i. U. thyreotropin were lower than that induced with 30 I. U. of the hormone. The T4 concentrations increased stronger and remained elevated longer in cows pretreated intrauterine with Lugol's solution than in untreated control cows. The experiments demonstrated that an intrauterine infusion of Lugol's solution may result in an increased activity of the thyroid gland. PMID- 4040286 TI - [Effect of a combination therapy of cisplatin and local irradiation on a mouse fibrosarcoma]. AB - The authors applied the method of regrowth delay in order to investigate the effect of a therapy combination consisting of cis-platinum and irradiation on the fibrosarcoma SSK2 in C3H mice. An independent addition of the effects of both therapy modalities was found. It could be shown especially that no elective radiosensitization of hypoxic tumor cells is caused by cis-platinum. PMID- 4040287 TI - Diabetic retinopathy in adolescent and teenage years. PMID- 4040288 TI - Proliferative sickle retinopathy in adolescent and teenage years. PMID- 4040289 TI - [C1 esterase inhibitor acquired deficiency: apropos of 4 cases]. PMID- 4040290 TI - Concomitance of urogenital with lymphoid and intestinal malignancies: more than a coincidence. AB - Concomitance of different primary malignant neoplasms in the same individual has been observed and explained by several possible mechanisms. For urogenital malignancies in concomitance with lymphoid or with intestinal malignancies some data indicate that common etiologic factor(s) with pleiotropic effects may be involved. Concomitance of these particular different primary malignant neoplasms must therefore be kept in mind in the evaluation of patients' conditions. PMID- 4040291 TI - Infectious complications after instrumentation of urinary tract. AB - Urethral catheterization is the single most important predisposing factor in the development of nosocomial urinary tract infection. Infection rates, etiologies, and possible methods of prevention are reviewed. Cystoscopy may be followed by a transient bacteremia. It is recommended that patients with positive urine cultures who undergo diagnostic cystoscopy receive antibiotic prophylaxis, but this is not required in patients with sterile urine. The incidence of urinary tract infection following transurethral surgery in patients who have not been given prophylactic antibiotics ranges from 6 to 60 per cent. The value of antibacterial prophylaxis in TUR, is still somewhat controversial. The incidence of infection and the value of antibacterial prophylaxis in prostatic biopsy appear to be related to the technique (transperineal or transrectal) used for the biopsy. It is too early to assess the infection risks associated with relatively new urologic procedures, such as ureteroscopy and percutaneous nephrostomy. Nevertheless, any procedure that crushes or manipulates a potentially bacteria harboring stone carries at least a theoretical risk of infection. PMID- 4040292 TI - Uterine rupture in the mare. PMID- 4040293 TI - [Penetrating capacity of bull spermatozoa in vitro]. AB - Studies were carried out on the penetrating capacity of bull spermatozoa in an estrous secretion, a modification of Kremer's method being employed by the authors. The new method seemed to be more readily applicable in the practice. It was found that the penetrating capacity was highest following thawing of semen at 39 degrees C, the pH value of the secretion being 6.8-6.9. The adding of the cytochrome C enzyme to the spermatozoa at the rate of 1 mg/cm3 of such semen increased the penetrating capacity by 22 per cent. When the thawed semen was allowed to stay for fifteen minutes the penetrating capacity of spermatozoa in the estrous++ secretion dropped by 33 per cent. PMID- 4040294 TI - [Hemostatic indices of oncological patients with different forms of jaundice]. AB - Such parameters of blood coagulability as levels of antithrombin III, plasminogen, plasminogen activator and fibrinogen were compared in patients suffering cancer of different localization (51), cholelithiasis (52), mechanical jaundice of uncertain etiology (57), acute biliary pancreatitis (17), cirrhosis of the liver (39) and healthy subjects. More cases of cancer and mechanical jaundice caused by factors other than cancer showed elevated levels of antithrombin III and fewer cases--normal ones. This was matched by relatively frequent normal concentrations of plasminogen, plasminogen activator and fibrinogen and a less frequent increase in the said levels. Changes in the levels of the four parameters of hemostasis were relatively more frequent in cancer patients. PMID- 4040295 TI - [Myocardial contraction and coronary circulation in experimental myocardial hypertrophy]. PMID- 4040296 TI - [Chronotherapy of patients with chronic dust-induced bronchitis]. PMID- 4040297 TI - [Diagnosis of idiopathic hypertrophic cardiomyopathy]. PMID- 4040298 TI - Splenectomy for thrombocytopenia. PMID- 4040299 TI - Accessory spleens: clinical significance with particular reference to the recurrence of idiopathic thrombocytopenic purpura. PMID- 4040300 TI - Tumors of the spleen. PMID- 4040301 TI - Trichuris muris: structure and formation of the egg polar plugs. AB - The structure and development of the polar plugs of Trichuris muris eggs were observed by light and electron microscopy. Initial stages in plug formation commenced in the spermatheca of the adult female where two polar papillae became delimited from the remainder of the oocyte cytoplasm. These papillae exhibited a discrete PAS positive reaction and were regarded as prospective plug regions from which cytoplasmic granules were absent. Glycogen rosettes, initially concentrated in these prospective areas, were later transformed into an irregular fine network of chitin-protein microfibrils. This arrangement of microfibrils was in contrast to that of the surrounding collar region which displayed a distinct lamellate organization. The fully developed polar plug was of lower electron density than the shell. Each plug was covered externally by the vitelline layer and lined internally by the lipid layer of the eggshell. PMID- 4040302 TI - [Developments in perinatal mortality in the last 25 years]. PMID- 4040303 TI - [Cardiotocography practice. Case 7]. PMID- 4040304 TI - Prolactin inhibits oestradiol-induced luteinizing hormone release at the pituitary level. AB - The direct action of prolactin (Prl) on pituitary LH secretion was studied by examining its effect on oestradiol (E2)-induced luteinizing hormone (LH) release from the rat pituitary in a perifusion system and determining the oestrogen receptor (ER) content of the pituitary in hyperprolactinaemic female rats. When the pituitary from rats in pro-oestrus was perifused with medium alone, 10(-7) M E2 significantly (P less than 0.05) increased the LH concentration in the effluent by 60-130% of the basal level, but in medium containing 1 microgram/ml Prl it did not cause LH release. In hyperprolactinaemic rats produced by implanting 2 anterior pituitary glands under the kidney capsule, the ER content of the cytosol of the pituitary (53.2 +/- 2.9 fmol/pituitary) was significantly increased (P less than 0.05), but that of the nuclei (6.8 +/- 0.2 fmol/pituitary) was significantly decreased (P less than 0.05) compared with the contents in rats in pro-oestrus. These data suggest that Prl has a direct suppressive effect on LH secretion from the pituitary in the rat, and that decreased translocation of ER into the nucleus might relate to impaired LH release by E2 from the pituitary of hyperprolactinaemic rats. PMID- 4040305 TI - Temporary increase in the circulating prolactin levels during and after consecutive administration of bromocriptine-mesilate (CB-154) in female mice. AB - Changes in circulating prolactin (Prl) levels during and after consecutive administration of bromocriptine-mesilate (CB-154; 0.2 mg/day), a potent suppressor of pituitary Prl secretion, were studied in virgin mice of SHN and BALB/c strains. Plasma Prl levels were lower in CB-154-treated SHN mice than in vehicle-treated controls until the first week of the daily treatment. However, the circulating Prl increased in the experimental mice and surpassed the control levels thereafter. The elevated levels of Prl were maintained throughout the treatment, then they decreased to control levels 1 month after the termination of the treatment. In BALB/c mice given CB-154, the pattern of changes of the circulating Prl levels was almost the same seen in SHN mice; a significant suppression of the Prl levels was observed on the 2nd day of the treatment and the levels increased and reached to the control levels thereafter. The results have demonstrated that in mice the inhibition of pituitary Prl secretion by CB 154 did not persist throughout the period of consecutive administration. PMID- 4040306 TI - Four cases of XX males: endocrine and clinical features. AB - G-banded chromosome preparations from four phenotypically male patients resulted azoospermic at semen analysis, showed no evidence of Y chromosome in 46,XX female constitution. At the andrological examination, the only common finding in them was the presence of very small testes. Serum levels of basal LH, FSH, prolactin and testosterone were evaluated. A subnormal response by testicular Leydig cells to HCG was observed. The LH and FSH responses to LHRH were similar to those of XXY controls, and the variation of prolactin levels after sulpiride stimulus was in the normal range. Seminal, histological and endocrine investigations show the primitive origin of the hypogognadism. PMID- 4040307 TI - The adrenergic innervation of the guinea pig ovary during prenatal and postnatal periods. AB - The pattern of adrenergic nerves was visualized and norepinephrine (NE) quantified in guinea pig ovaries from fetal day 50 to term and on days 1, 5, 10, 20 and 28 postnatally. Before birth, there were a few perivascular adrenergic nerves and correspondingly low ovarian NE levels. After birth and through day 20, nerves gradually grew into adjacent stroma. By day 28, there was a proliferation of beaded adrenergic nerves around blood vessels and into adjacent stroma, which was reflected by significantly increased ovarian levels of NE. These findings are discussed in relation to antral follicle development, atresia, and interstitial gland formation in the ovaries of prepubertal guinea pigs. PMID- 4040308 TI - Substructures of paired helical filaments from Alzheimer's disease neurofibrillary tangles. AB - Presented studies reveal that each of the approximately 10 nm filaments forming the paired helical filaments (PHF) is made up of four protofilaments. Each of the protofilaments is a beaded structure, consisting of globules connected by longitudinal bars. A cross-view of PHF shows eight globules linked by transverse bars. The transverse bars are shorter than the longitudinal bars. Comparison between PHF and neurofilament protofilaments indicates structural differences between these profiles, i.e., the globules making the PHF protofilaments are larger and the longitudinal bars are longer than those in the normal neurofilaments. A three-dimensional diagram of PHF structure is presented. PMID- 4040309 TI - The human Eustachian tube lumen in children. I. The isthmus. AB - A study of Eustachian tube measurement in infants and children is presented. The study comprised 53 Eustachian tubes from normal temporal bones and 17 Eustachian tubes from temporal bones harbouring acute and secretory otitis media. The temporal bones underwent histologic serial sectioning. The lumen of the Eustachian tube isthmus was measured with the aid of a grid mounted on a microscope. These measurements show: A) the Eustachian tube isthmus lumen does grow and enlarge slightly with age; B) each age group presents a considerable range in area, compatible with a natural biological distribution; C) no statistical difference was found in the size of isthmus lumens obtained from temporal bones which had been affected by acute or secretory otitis media, when compared with lumens of Eustachian tubes coming from non-pathological ears. This comparison took into consideration both age and physiological distribution. PMID- 4040310 TI - Cis-diaminedichloro platinum ototoxicity. An experimental study. AB - Four groups of guinea pigs received different doses of cis-platinum. SEM and TEM showed a direct relation between the dose and the damage. The first row of OHC is the first one to be damaged. The IHC are more resistant than the OHC. The pattern of destruction is similar to the one produced by the aminoglucoside antibiotics. PMID- 4040311 TI - Induction of human labor at term: uterine activity, inducibility, duration and neonatal jaundice. AB - A total of 821 patients, 39-40 weeks pregnant, was obstetrically normal at admission. In 212 of them intra-uterine pressure (IUP) was monitored before and during inducing labor by oxytocin, in 212 patients delivery was also induced by oxytocin but not monitored, in 197 by combining oxytocin and amniotomy, and 200 had spontaneous delivery. Inducibility could be predicted by uterine baseline activity and a 50 mu i.v. shot of oxytocin, together with determination of cervical status and placental location. The duration of labour induction was affected by parity, placental location and cervical status, but was predicted only to a minor degree by baseline activity and uterine oxytocin sensitivity. Amniotomy did not affect caesarean, section rate. The newborn child benefited from IUP monitoring: fewer transfers to pediatrics were necessary, there was less neonatal jaundice and fewer blood exchanges. It is assumed that if labor is not monitored through IUP, oxytocin may cause neonatal hyperbilirubinaemia through episodes of increased uterine resting pressure. PMID- 4040313 TI - The psychosocial impact of high risk pregnancy. PMID- 4040312 TI - [New derivatives of 7- and 8-member perhydrocyclic compounds. II. Studies on the effect on the central nervous system and circulatory system of new derivatives of perhydro-1,4-oxazepine, perhydro-1,4-diazepine, perhydro-1,4,5-oxadiazepine and perhydro-1,5-oxazocine containing the 2-guanidinoethyl group]. PMID- 4040314 TI - The effects of antimitotic and microfilament disrupting agents on functions of isolated guinea-pig parietal cells. AB - In isolated guinea-pig parietal cells pretreated for 60 min with the H2 antagonist ranitidine, the antimitotic agents colchicine and vinblastine, the microfilament-disrupting agent cytochalasin B resulted in a concentration dependent inhibition of histamine-stimulated acid secretion up to 80%. Ranitidine reduced histamine binding to the membrane located H2-receptor. The anti cytoskeletal agents inhibited the cellular histamine uptake but did not effect the histamine methyltransferase activity which was significantly reduced by ranitidine. The data suggest that cytoskeletal elements like microtubules and microfilaments are of very specific functional significance not only in the secretory process of the parietal cell but also for cellular transport mechanisms. PMID- 4040315 TI - [Effects of combination chemotherapy with cis-diamminedichloroplatinum (II) (CDDP) on renal function in patients with urogenital malignancies]. AB - The renal function in 23 patients with advanced urogenital cancers (10 testicular, 8 uroepithelial, 3 prostatic cancers and 1 penile cancer) treated with a total of 3 or 4 cycles of combination chemotherapy including CDDP was examined prospectively, by measuring of creatinine clearance (Ccr), fractional excretion of beta 2 microglobulin (FE beta 2 MG) and urinary N-acetyl-beta glucosaminidase (NAG). Patients with testicular cancers (group 1) who received the cumulative CDDP dose of 360-1966 mg (on average 868 mg), the decrease in Ccr and increase in FE beta 2 MG and NAG were temporary during each chemotherapy cycle. However, in the overall course, after the cumulative dose exceeded 600 mg, higher beta 2 MG excretion persisted and after the cumulative dose exceeded 800 mg, Ccr decreased to 30% of the pretreatment level. This suggests cumulative delayed, irreversible renal damage. The severity of decrease in Ccr paralleled the increase in cumulative CDDP dose. Patients with urogenital cancers other than testicular cancer (group 2) who received the cumulative CDDP dose of 80-480 mg (on average 217 mg), and who had decreased Ccr and tubular damage prior to treatment, even though the cumulative dose was lower than in group 1, changes in Ccr, FE beta 2 MG and NAG were almost in the same magnitude as in group 1. Determination of NAG is useful for detection of the early change in the tubules several days after CDDP administration, while that of beta 2 MG is useful for detection of the chronic damage of renal tubules after several cycles of CDDP chemotherapy. CDDP nephrotoxicity is characterized by dose-dependent tubular damage. Although renal injury may not be evident during the early course of treatment, repeated courses of CDDP may lead to clinically serious chronic renal failure. PMID- 4040316 TI - Squamous metaplasia of the trigone in women with recurrent cystitis syndrome. AB - Urocystic mucosal biopsies of the white patch on the trigone in 44 women complaining of dysuria and frequency with or without bacteriuria showed varying degrees of squamous metaplasia as well as submucosal fibrosis. The patients with more frequent episodes of such symptoms in the past had more severe squamous metaplasia with submucosal fibrosis. Introital bacteria were found in almost all patients with mild or moderate development of squamous metaplasia, but not in those with severe lesions. These facts suggest that introital bacteria may be one of the causative factors for the initiation and early development of these abnormal mucosal changes. However, the further progression to severe mucosal alteration seems to be independent of any bacteria and this severe mucosal alteration may result in recurrence of such symptoms. PMID- 4040317 TI - A rare case of adenocarcinoma of bladder following augmentation enterocystoplasty. AB - This is a report of a case of poorly differentiated adenocarcinoma found 20 years after bladder augmentation ileoplasty. The origin of this tumor was proved to be the ileal part of bladder augmentation. Autopsy revealed metastatic lesions in the stoma (sigmoid conduit), lungs, liver, left femur, adrenal glands and lymph nodes. A review of the literature revealed only one other such case. This is a rare case of adenocarcinoma in the ileal part of bladder augmentation. PMID- 4040318 TI - Urinary tract calculi in pregnancy. PMID- 4040319 TI - Improved evaluation of hypertrophic cardiomyopathy by biventriculography with axial projection. AB - To delineate the precise anatomic abnormalities of the interventricular septum (IVS), mitral valve (MV), and left ventricular posterior wall (LVPW) in patients with hypertrophic cardiomyopathy (HCM), we used axial biventriculography (BVG) (hepato-clavicular projection: angled BVG) to examine 17 patients with HCM and four with concentric hypertrophy due to systemic hypertension. We also examined 9 of these 21 patients with conventional left anterior oblique (LAO) BVG (non angled BVG). The IVS and along axis of the LV cavity when measured by angled BVG were significantly longer than when measured by non-angled BVG. The IVS, MV, and LVPW were better seen in profile in angled than in non-angled BVG. In two patients with HCM with obstruction (HOCM), systolic anterior motion of the anterior leaflet of the MV was readily identifiable with angled BVG, which is usually not the case with non-angled BVG. Thus, angled BVG is superior to conventional LAO BVG in the angiographic assessment of patients with HCM. PMID- 4040320 TI - Usefulness of Doppler echocardiography for determining hemodynamic improvement with intravenous verapamil in hypertrophic cardiomyopathy. PMID- 4040321 TI - Trans fatty acids in human milk lipids: influence of maternal diet and weight loss. AB - Geometric and positional isomers of octadecanoic acid in milk expressed during the first 9 weeks of lactation were determined for mothers delivering prematurely (PT) and at term (FT). Total C18:1 concentration was lower in PT than FT milk. C18:1 trans (elaidic acid) content was higher in PT and FT colostrum compared with subsequent milk samples. No relationship was observed between C18:1 trans level in milk and oleic acid, linoleic acid, total fatty acid levels, or volume of milk expressed. While gestational age and lactational stage appeared to affect the trans fatty acid pattern, the overriding influence was rate of maternal postpartum weight loss. Effect of weight loss on milk trans fatty acid levels was independent of maternal diet. Trans fatty acid content of milk as a function of recent maternal fat intake was also demonstrated. This study indicates that infants receiving human milk ingest levels of trans fatty acids reflecting short and long term maternal diet. PMID- 4040322 TI - Declining fertility in England and Wales as a major cause of the twentieth century decline in mortality. The role of changing family size and age structure in infectious disease mortality in infancy. AB - The decline in infectious disease mortality in England and Wales beginning about 1880 has been attributed to improved nutrition, hygiene, and sanitation. Such an explanation does not adequately explain the lack of improvement in infant and diarrheal disease mortality before 1900 nor the abrupt subsequent decline. A hypothesis was proposed that the decline in fertility rate was a major cause of the decline in infant mortality by raising the median age at infection. The hypothesis could only be tested indirectly. A review of morbidity data demonstrates the importance of family characteristics on the median age at infection for measles, pertussis, and common respiratory illness. The association of parity with infectious disease mortality supports the hypothesis. A method was developed for estimating the change in birth order distribution resulting from declining fertility. Using 1949-1950 data, it was shown that declining fertility could account for at least a 24% decline in postneonatal mortality due to bronchitis and pneumonia. Age-specific measles mortality rates are consistent, with an increase in age at infection. Declining fertility appears to have played a major role in the decline in infectious disease mortality in England and Wales by increasing the median age at infection. PMID- 4040323 TI - A simple randomized response device. PMID- 4040324 TI - College of pharmacy-teaching hospital relationships: report of a survey. AB - The results of surveys conducted by the American Association of Colleges of Pharmacy (AACP) and the American Society of Hospital Pharmacists (ASHP) to investigate the extent and causes of problems in relationships between colleges of pharmacy and the pharmacy departments in their affiliated teaching hospitals are presented. For the AACP study, questionnaires were mailed to either the dean or the pharmacy practice department chairman of all 72 colleges, and a telephone interview was subsequently conducted with most of them. For the ASHP study, interviews were conducted with 67 directors of pharmacy in the colleges' principal affiliated teaching hospitals. Problems identified by the colleges related to quality or extent of services and finances. Most directors of pharmacy stated that they derived benefit from their affiliation with a college of pharmacy. The relationship between colleges of pharmacy and their teaching hospitals is relatively healthy and generally better than expected. PMID- 4040325 TI - College of pharmacy-teaching hospital relationships: panel discussion. PMID- 4040326 TI - Medicine and law. A symbiotic relationship? PMID- 4040327 TI - Cryoprecipitate therapy in amniotic fluid embolization. PMID- 4040328 TI - Sibs with the fetal akinesia sequence, fetal edema, and malformations: a new syndrome? AB - Pena and Shokeir [J Pediatr 85:373-375. 1974] first described a syndrome characterized by multiple ankyloses, camptodactyly, facial anomalies, and pulmonary hypoplasia, which was later termed Pena-Shokeir I syndrome. Recent evidence suggests that a more accurate designation for this condition is the fetal akinesia sequence, which is almost certainly a heterogeneous entity. We describe sibs who were diagnosed as having Pena-Shokeir I syndrome but who did not have the muscular or anterior horn cell changes characteristic of other infants with the fetal akinesia sequence. In addition, both sibs had fetal edema, the first sib had coarctation of the aorta, and the second had polydactyly and thyroid hypoplasia. We suggest that this case provides further evidence for heterogeneity in the fetal akinesia sequence and may represent a provisionally unique syndrome. PMID- 4040329 TI - Human lymphoblastoid interferon in the treatment of advanced epithelial ovarian malignancies: a Gynecologic Oncology Group Study. AB - The purpose of this study was to evaluate the toxicity and antitumor activity of low doses of human lymphoblastoid interferon in 36 patients with measurable disease in whom higher priority treatment methods had failed. All but one had surgically confirmed advanced disease and had undergone initial treatment with a multiagent chemotherapeutic regimen in combination with cisplatin; four patients had also received radiation therapy. Their age range was 28 to 74 years. All had Gynecologic Oncology Group performance grade 2 or better (Karnofsky, 50% and above). Human lymphoblastoid interferon was administered at 5 megaunits/m2 intramuscularly, for 5 days per week (Monday through Friday) for 6 consecutive weeks. Patients who exhibited response or stable disease at 6 weeks were placed on a regimen of maintenance therapy at the same dose level for 2 days per week (Monday and Tuesday), for up to 12 months or until progression. Twenty-eight patients were evaluable for response: two with complete responses (7.1%), three with partial responses (10.8%), 14 with stable disease (50.0%), and nine with increasing disease (32.0%). Among the cumulative adverse effects, fatigue was most common, followed by moderate leukopenia and thrombocytopenia. Other observed adverse effects consisted of severe nephrotoxicity in two patients and myocardial infarction in one patient. It appears that therapy with human lymphoblastoid interferon may have cytostatic and possibly cytotoxic effects in this group of patients, with acceptable adverse reactions. PMID- 4040330 TI - Vasopressin withdrawal produces hypotension in the spontaneously hypertensive rat. AB - In spontaneously hypertensive rats (SHR) and their normotensive Wistar-Kyoto controls (WKY), prolonged intravenous infusions of either arginine vasopressin (AVP, 8 mU X kg-1 X min-1) or phenylephrine (PE, 20 nmol X kg-1 X min-1) resulted in similar rises in arterial pressure. Heart rate fell greatly in the WKY but not in the SHR. Withdrawal of the PE infusion resulted in moderate decreases in blood pressure and increases in heart rate; these responses were similar in SHR and WKY. At 5 h after PE withdrawal, blood pressure and heart rate returned to basal values. In contrast, withdrawal of the AVP infusion was associated with greater falls in blood pressure and rises in heart rate. Blood pressure and heart rate in both the SHR and the WKY at 5 h after AVP were significantly different from their respective basal values. The effects of AVP withdrawal on either blood pressure or heart rate were significantly greater in the SHR than in the WKY. At 5 h after the withdrawal of AVP, blood pressure in the SHR was reduced to normotensive levels. These results suggest that the withdrawal effect was specific to AVP, was more marked in the SHR, and might not result from only the rise in blood pressure seen during the intravenous infusion of the pressor agent. PMID- 4040331 TI - Management of nipple discharge by clinical findings. AB - In a review of 249 office patients who complained of nipple discharge, breast nodularity and duct ectasia was the cause in three quarters. The clinical diagnosis was made by observing that more than one duct was involved and by the color of the discharge. On average, the patients were 10 years younger than those with cysts and 20 years younger than those with carcinoma. In half, the discharge could persist or recur for months or years. Nipple discharge was not commonly associated with carcinoma, and when it was, the carcinoma was almost always palpable. Nipple discharge, including bloody discharge, should be regarded as a sign of a benign breast disorder, not of breast cancer. Duct papillomas can be recognized by exploring the single profusely discharging duct, regardless of the color of the discharge. Other than patients with an obvious lump, the only patients who require surgical exploration are those with a single profusely discharging duct, not because cancer is a significant possibility but merely to rid the patient of the nuisance of the continuing discharge from a duct papilloma. Of 249 patients with nipple discharge, breast nodularity and duct ectasia was the cause in 75 percent. The median age of these patients was the mid 30s. The discharge was chronic or recurring in half. Only 4 percent of all the patients with nipple discharge had an associated breast cancer. When cancer was present, an obvious lump was usually palpable. Bloody discharge was much more likely to be associated with benign breast disorders than cancer. A single profusely discharging duct should be explored regardless of the discharge color because of the likelihood of finding a duct papilloma. PMID- 4040332 TI - The middle ear mucosal immune system in otitis media with effusion. AB - The mucous membrane of the middle ear cavity in otitis media with effusion has a number of immunobiological mechanisms capable of defending the organ. A humoral immune mechanism, with all the attributes of a local mucosal immune system, appears to be present and capable of preventing viral and bacterial access to middle ear tissue. Putative cells of a cell-mediated immune response also appear to be present, and the distribution of T cells and B cells and T-helper and T suppressor cells is described. The exact role of these cells in either cell mediated immunity or delayed hypersensitivity remains to be defined in otitis media. Lymphocyte--macrophage interaction is briefly described and may represent an important aspect of immune modulation in the middle ear in otitis media with effusion. Finally, the effect of middle ear supernatants on natural killer cell activity is discussed. Serous effusions appear to augment natural killer cell activity of peripheral blood lymphocytes. PMID- 4040333 TI - Fluid and fibrosis in the human middle ear. AB - Temporal bones from 12 cases of adult otitis media with effusion were studied for the process of fibrosis. There were three types of fibrotic courses, including total replacement of fluid and complete obliteration of middle ear spaces. Thus, the author concluded that effusion, tissue proliferation, fibrosis, and adhesions of the tympanic membrane are sequential findings of otitis media with effusion. PMID- 4040334 TI - Secretory otitis and pneumatization of the mastoid process: sexual differences in the size of mastoid cell system. AB - Seventy-nine children (41 girls and 38 boys) were subjected to tympanometry nine times from the age of 2 years to the age of 7 years. In addition, otoscopy was performed, and the children's otologic history was recorded. At the age of 7 years, roentgenograms were taken of the mastoid process, and the area of the air cell system was measured by planimetry. The smallest cell systems were found in ears with a history of secretory otitis or chronic tubal dysfunction--a finding which supports the environmental theory of pneumatization. Boys had significantly smaller cell systems (mean, 7.5 cm2; range, 2.75-16.75) than girls (mean, 9.0 cm2; range, 2.5-15.7). The degree of middle ear pathology was significantly higher in boys, as expressed by the total tympanometric score. The more pronounced middle ear pathology in boys was caused by more frequent and severe episodes of upper respiratory tract infections. The analysis of the sex differences provides substantial support of the environmental theory of pneumatization, since upper respiratory tract infections in childhood often cause tubal dysfunction and secretory otitis, conditions that disturb the normal process of pneumatization and result in hypocellularity. PMID- 4040335 TI - Mucociliary dysfunction in experimental otitis media with effusion. AB - To investigate the morphologic changes of the eustachian tube mucociliary transport systems, experimental otitis media with effusion was induced by immune complex injection into the bullae of experimental animals. Horseradish peroxidase was chosen as an antigen because of its high antigenicity and traceability under light and electron microscopy. Seventy-three guinea pigs and 41 chinchillas were divided into three groups: active Arthus group, passive Arthus group, and control group. Animals were killed under general anesthesia from the first to 30th day after the injection. Within 5 days after injection, effusions were observed consistently in all animals, but in only 80 per cent on the 7th day and in only 50 per cent after the 10th day after injection. The most conspicuous findings were that the interciliary space of the mucociliary system was diffusely occupied by an electron-dense mucus, and the upper part of the ciliary shafts were tightly glued together. These features seem to indicate rheologic alterations of the mucus and a disorder of its coupling to the cilia. This study strongly suggests that the mucociliary coupling disorder caused by altered rheologic properties of the mucus causes clearance dysfunction of the eustachian tube, resulting in middle ear effusion. The various inflammatory products contained in the middle ear effusions elicit a persistent vicious cycle of inflammatory reactions in the tubotympanum. PMID- 4040336 TI - Pumping and clearance function of the eustachian tube. AB - The purpose of this study was to clarify the relationship between mucociliary and muscular clearance in the eustachian tube. Displacement of various viscosities and volumes of a colored fluid through the tube was observed endoscopically in cats. To test ciliary clearance, the fluid was placed in either the tympanum or the mastoid bulla. The interval between the instillation and beginning of discharge of the fluid from the pharyngeal orifice of tube was measured. Clearance time was prolonged with fluids having high viscosities, and the clearance time from the tympanum was shorter than that from the mastoid bulla. To test muscular clearance, the tensor veli palatini muscle was stimulated electrically to simulate swallowing, and the number of contractions necessary for massive discharge of the fluid was counted. Massive discharge occurred only with low viscosity fluid placed in the tympanum, whereas small amounts of highly viscous fluid were cleared by linear discharge. The authors concluded that when the volume of middle ear effusion was small, the fluid was cleared by mucociliary clearance. When the volume of fluid was large, the low viscosity fluid was cleared by muscular clearance only, while highly viscous fluid was cleared both by ciliary and muscular clearance. PMID- 4040337 TI - Age and adenoid size in relation to adenoidectomy in otitis media with effusion. AB - A previously reported study showed that adenoidectomy resolved effusions in chronic bilateral otitis media with effusion in 36 to 46 per cent of 103 children. This work includes 52 additional cases and assesses the effect of age and adenoid size in relation to adenoidectomy. Pre-operative lateral cephalometric radiographs showed the adenoid size and postnasal space airway. Surgery was allocated randomly into three groups: adenotonsillectomy, adenoidectomy, and no surgery. In addition, in all cases a unilateral myringotomy and ventilating tube insertion were performed. The ear not operated upon was assessed for clearance of the effusion at 3, 6, 9, and 12 months postoperatively. Following adenoidectomy the effusion resolved in the ear not operated upon in 31 to 45 per cent of cases assessed after 1 year. Tonsillectomy conferred no additional benefit. There was a trend for improved clearance of effusions in children more than 6 years of age, compared with those less than 6 years of age. There was also a trend for improved clearance after removal of larger adenoids from children with smaller postnasal space airways, but this was only significant for 3 months postoperatively. PMID- 4040339 TI - [Monitoring changes in the heart rate of the premature fetus during tocolysis with the beta-adrenomimetics partusisten and Pre-par]. PMID- 4040338 TI - Treatment of chronic otitis media with effusion: results of tympanostomy tubes. AB - Insertion of tympanostomy tubes to provide prolonged aeration and drainage of the tympanum in cases of chronic secretory otitis media has become the most commonly performed operation in children. To investigate the therapeutic efficacy of current treatments of chronic secretory otitis media, the authors undertook a randomized clinical trial with four treatment arms: myringotomy alone, tympanostomy tubes, adenoidectomy and myringotomy, and the combination of adenoidectomy and tympanostomy tubes. This report describes the preliminary (one year) outcome in the group of children who were treated with tympanostomy tubes. The observed average differences between the myringotomy and tympanostomy tube groups were small, with the exception of one variable (time to first recurrence). Although the clinical importance of these differences remains to be established, the authors believe they are substantial enough to justify continued use of tympanostomy tubes in the primary surgical therapy of chronic secretory otitis media, when medical therapy and observation indicate the need for drainage to improve hearing or correct anatomic deformities of the tympanum. PMID- 4040340 TI - Teratological examination of Wofatox 50 EC (50% methylparathion) on pheasant embryos. AB - Wofatox 50 EC is a widely used experimental insecticide, which can expose the pheasants (non-target organisms) during the plant protection practice. The test material was employed in 4 different aqueous emulsions, of which the 2 lowest level (0.2 and 0.4%) corresponded to the concentrations used in plant protection. The total volume of injected emulsions was 0.1 ml per egg on the 12th d of incubation. The macroscopic results showed a dose-dependent maldevelopment (generally cervical lordosis and scoliosis, cyllosis and sporadic thoraco gastroschisis). PMID- 4040342 TI - [Physiology of hemostasis]. PMID- 4040341 TI - Permeability studies of the guinea pig placental labyrinth. II. Tracer permeation and freeze-fracture of fetal endothelium. AB - Permeability of the fetal endothelium within the guinea pig placental labyrinth is studied by means of horseradish peroxidase (HRP) and ionic lanthanum as diffusion tracers. The paracellular transport of HRP is restricted by the occluding junctions of the fetal endothelium. In contrast, ionic lanthanum readily permeates most of the intercellular junctions and rapidly infiltrates the basal lamina. Freeze-fracture replicas reveal zonulae occludentes connecting the fetal endothelial cells. The network of the zonulae occludentes is variable, exhibiting highly complex areas as well as single strand interconnections. A correlation between the permeability studies and freeze-fracture findings is discussed. PMID- 4040343 TI - Parasites in lungs of dead equids in Kentucky: emphasis on Dictyocaulus arnfieldi. AB - Prevalence of natural infections of parasites from the lungs of 488 dead Thoroughbreds in Kentucky was investigated. The horses varied from 1 to 32 years of age; 419 horses were from 215 farms and 69 horses were from 68 individual sources for which a specific farm was not identified. Examinations of the lungs were made from Mar 1, 1983 through Feb 29, 1984. Dictyocaulus arnfieldi was recovered from 56 (11%) of the horses. Other parasites found were larvae of Parascaris equorum in 37 (8%) and of Habronema/Draschia in 67 (14%) of the horses. The possible effect of ivermectin treatment on the prevalence of D arnfieldi in the lungs is discussed. Presence of D arnfieldi in 20 other selected dead equids was also investigated. PMID- 4040344 TI - Allergic bronchopulmonary curvulariosis. AB - A patient with clinical and roentgenographic findings suggestive of allergic bronchopulmonary disease who presented with recurrent pulmonary infiltrates with peripheral eosinophilia was identified. Sputum cultures were positive for Curvularia lunata. Total serum IgE was elevated, and intracutaneous skin testing with C. lunata was positive. Serum precipitins against C. lunata were present with specific IgE and IgG antibody indexes elevated. These studies provide further Immunologic characterization of this uncommon disorder. PMID- 4040345 TI - Age-related variation of respiratory chemosensitivity in monozygotic twins. AB - To examine age-related variations in respiratory chemosensitivity to hypoxia and hypercapnia, the magnitudes of within-pair variances for ventilatory responses to hypoxia and hypercapnia were measured in 38 pairs of male monozygotic twins. Mean values for the slope factor of end-tidal PO2-ventilation hyperbola (A) were larger in Group I (13 pairs with a mean age of 16.3 +/- SD 0.9 yr) than those in Group II (12 pairs with a mean age of 29.8 +/- 6 yr), and Group III (13 pairs with a mean age of 46 +/- 7.2 yr). The slope factors for end-tidal PCO2 ventilation line (S) were similar among the 3 groups. Within-pair variances for A, A/body surface area (BSA), and Vo (asymptote for ventilation when end-tidal PO2 is infinite) were larger in Groups II and III than in Group I. Within-pair variances for S and S/BSA were also larger in Groups II and III than in Group I, whereas within-pair variances for B (intercept with end-tidal PCO2) were similar among the 3 groups. These results indicate that variations for respiratory chemosensitivity to hypoxia increase during the period from adolescence to adulthood and stay at a similar level thereafter. Variations of hypercapnic chemosensitivity also increase during this period, attenuating thereafter; however, the variation is 7 times larger than that of hypoxic chemosensitivity in the third and fourth decades. PMID- 4040346 TI - Use of chloramphenicol in the United States. PMID- 4040347 TI - [Apical hypertrophic myocardiopathy. Apropos of 10 cases]. AB - Apical hypertrophic cardiomyopathy is a recently defined subgroup of primary hypertrophic cardiomyopathy. Ten new cases are studied. The electrical features (anomalies of repolarisation) were constant and giant negative T waves were observed in 3 out of 10 cases. Two-dimensional ultrasonography confirmed the diagnosis in every case; the optimal views consisted of 4 cavity scans obtained by the apical approach. When angiography was performed (7 cases out of 10), it confirmed the ultrasonographic findings and was able to eliminate any coronary artery lesions. The patients had a mean age of 48.3 years with a marked male predominance (sex ratio of 0.8) and all of the patients are alive with a mean follow-up of 3.4 years. The functional handicap was moderate (class III: 1 case, class II: 5 cases and class I: 4 cases) and did not progress during the period of follow-up. The family surveys performed revealed that apical hypertrophy can be integrated into the spectrum of segmental hypertrophic cardiomyopathy. In two cases, this survey revealed the coexistence in the same family of segmental hypertrophy with different topography. The long term prognosis of this disease is unknown and the authors consider that the risk of ventricular arrhythmia justifies routine rhythmological evaluation in order to guide subsequent treatment. PMID- 4040348 TI - [Diagnosis and echocardiographic course of infectious endocarditis in obstructive cardiomyopathy]. AB - A typical case of advanced obstructive cardiomyopathy in a young subject was revealed by Streptococcal mitral valve endocarditis and was diagnosed by one and two dimensional echocardiography, which revealed a pedunculated vegetation on the large mitral valve and rupture of the chordae of the small mitral valve. This was complicated by biventricular heart failure, peripheral arterial embolism in the leg due to migration of the vegetation which disappeared on the repeat echocardiography and pulmonary embolism with arterial clot emboli due to heparin induced thrombocytopenia. This condition resolved without requiring cardiac surgery. Patients with obstructive cardiomyopathy should be treated routinely with prophylactic antibiotics, particularly when dental treatment is required. Echocardiography has become an essential examination in the diagnosis of this disease and its complications, especially in cases with infectious endocarditis. PMID- 4040349 TI - Timing of combined hyperthermia and 1,3-bis(2-chloroethyl)-1-nitrosourea or cis diamminedichloroplatinum in BD IX rats with BT4A tumours. AB - Groups of 7-10 evaluable BD IX rats with the neurogenic BT4A tumour on the right hind leg were treated with waterbath hyperthermia (44 degrees C, 60 min) in combination with 1,3-bis (2-chloroethyl)-1-nitrosourea (BCNU) 20 mg/kg or cis diamminedichloroplatinum (cis-DDP) 3 mg/kg i.p. at different sequences and timing within +/- 24 hr. Tumour responses were evaluated by tumour doubling time and clinical criteria, toxicity by toxic deaths, weight loss, and local skin reactions. With both BCNU and cis-DDP, tumour response was markedly dependent on timing; the greatest effects were obtained giving hyperthermia just after the drug. Local side effects were not different in the timing groups, but cis-DDP general toxicity was most severe when cis-DDP was given just before hyperthermia. PMID- 4040350 TI - Effect of cis-platinum on kidney cytochrome P-450 and heme metabolism: evidence for the regulatory role of the pituitary hormones. AB - A novel action of the gonadotropic hormones of the adenohypophysis on the regulation of kidney heme metabolism and cytochrome P-450 concentrations is described. The treatment of rats with cis-platinum for 7 days caused a greater than twofold increase in the microsomal cytochrome P-450 and heme concentrations in the kidney. The sodium dodecyl sulfate-gel electrophoresis of the microsomal preparation revealed increased levels of both apocytochrome P-450 and heme in the molecular weight region corresponding to cytochrome P-450. In hypophysectomized rats, similar increases in heme and the cytochrome contents in the kidney were observed. Conversely, the treatment of rats with human chorionic gonadotropin (hCG) fully reversed the effect of cis-platinum on heme and cytochrome P-450 concentrations. The cellular basis of increases in concentrations of heme and the hemoprotein was explored by measuring the incorporation of [14C]glycine-labeled hemoglobin heme into the kidney microsomal heme fractions. In comparison with the control rats, the specific 14C activity of heme in microsomal fraction was not increased. Moreover, the effect of cis-platinum on kidney cytochrome P-450 appeared to be unrelated to alterations in the activities of the rate-limiting enzymes of heme biosynthesis and degradation pathways, delta-aminolevulinate synthetase, and heme oxygenase, respectively. On the other hand, ferrochelatase activity and the concentration of total porphyrins in the kidney were profoundly altered by cis-platinum treatment; a twofold increase in ferrochelatase activity and a marked reduction (40%) in the total porphyrin concentration were observed. Also, the activities of uroporphyrinogen-I synthetase and delta-aminolevulinate dehydratase were decreased in cis-platinum-treated animals. The latter effects reflect a direct inhibitory action of cis-platinum. It appears that the cis platinum-mediated increase in the microsomal heme concentrations involves an accelerated rate of heme production as a consequence of increased ferrochelatase activity. This, in turn, could increase the production of cytochrome P-450. It is suggested that the anterior pituitary hormones control the concentration of the cytochrome P-450 in the kidney, and this process may be interrupted by cis platinum. PMID- 4040351 TI - Accessibility of sulfhydryl residues induced by cytochalasin B binding and conformational dynamics in the human erythrocyte glucose transporter. AB - Studies with intact cells have implicated essential sulfhydryl groups in the carrier-mediated glucose transport of human erythrocytes. In an attempt to identify and characterize such essential sulfhydryl residues we have studied the interaction of p-chloromercuribenzoate (PCMB) with a purified glucose transporter preparation (band 4.5) from human erythrocytes, in the presence and absence of its ligands, and the effects of this interaction on the binding of cytochalasin B (CB) to the transporter. At least 3 mol of PCMB reacted per mol of this preparation. A portion of the reaction was significantly enhanced in the presence of cytochalasin B. This enhancement was a saturable function of CB concentration, and was half-maximal at a CB concentration equal to the dissociation constant for the CB binding to the preparation. This CB-sensitive, PCMB reaction product comigrated with the band 4.5 on lithium dodecyl sulfate-polyacrylamide gel electrophoresis. An excess of D-glucose did not affect the PCMB reaction by itself in the absence of CB, but totally abolished the CB-induced enhancement of the PCMB reaction. PCMB inhibited the CB binding activity of the transporter preparation, and this inhibition was also enhanced in the presence of CB. These results suggest that CB binding perturbs the conformational dynamics of the glucose transporter resulting in an exposure of at least two sulfhydryl residues to PCMB reaction, and that some of these CB-sensitive sulfhydryl groups are essential for CB binding to the transporter. PMID- 4040352 TI - [The evaluation of single administration of cisplatin in non-small cell carcinoma of the lung]. AB - The effects of chemotherapy by single administration of Cisplatin were studied in 26 patients with non-small cell carcinoma of the lung. There were 22 males and 4 females with a median age of 63 years. 21 cases were epidermoid carcinoma, 4 cases were adenocarcinoma and 1 case was atypical carcinoid. Cisplatin 20 mg/m2 with hydration and diuresis was given daily for 5 consecutive days. The course was repeated every 3 weeks. Partial response was observed in 4 patients (3 epidermoid carcinoma and one atypical carcinoid). The response rate was 19%. Side effects induced by Cisplatin were gastrointestinal toxicity including vomiting, nausea and appetite less, bone marrow toxicity and renal damage. These were not so severe, and reversible. Gastrointestinal toxicities were controlled successfully by corticosteroids. In 12 patients gastrointestinal toxicities were not observed. We conclude that Cisplatin is effective for non-small cell carcinoma, especially for epidermoid carcinoma. Hematologic toxicities of Cisplatin were not so severe. Therefore, combination chemotherapy including Cisplatin would improve the quality of life of patients suffering from non-small cell carcinoma of the lung. PMID- 4040353 TI - Ulcerating tumor involving the auricular area. PMID- 4040354 TI - Epidemiology of facial clefting. AB - An analysis was performed of patients with facial clefts notified between 1960 and 1982 to the Liverpool Congenital Malformations Registry. From 1960-82 there were 325 727 births in the area surveyed and 544 cases of facial clefting were notified. When 88 patients with recognised syndromes and multiple congenital anomalies were excluded, the overall prevalence of facial clefts alone was 1.4 per 1000 total births. This group was then classified further into 137 cases of cleft lip alone, 166 cases of cleft lip and palate, and 153 cases of cleft palate alone. The prevalence of these groups per 1000 total births is 0.42, 0.51, and 0.47 respectively. There were some fluctuations in annual prevalence with rises being observed in the mid and late 1960s and mid and late 1970s. There was a noticeable male predominance in the cleft lip and cleft lip and palate groups of 1.52:1 and 1.98:1 respectively, with a 1:1 ratio in the cleft palate group. There were no significant differences in birthweight and mean maternal age in the three groups. In the cleft palate group, however, there was a significant trend towards an increase in the frequence of conception in the second half of the year. There was a maternal history of epilepsy in 4.4% of the cleft lip and 3% of the cleft lip and palate groups but only in 1 patient (0.6%) in the cleft palate group. The study illustrates the importance of environmental factors in the aetiology of facial clefting. PMID- 4040355 TI - Intolerance to cisplatin--a case report. AB - A patient who had a systemic reaction to cisplatin chemotherapy had a reaction to subsequent i.c. and i.v. test doses. Notwithstanding she had a more severe systemic reaction during a further course of cisplatin chemotherapy. PMID- 4040356 TI - [Quantitative informational estimation of the degree of liver damage on a model of chronic alcoholic intoxication]. AB - In the rat liver at a chronic alcoholic intoxication produced with various doses of ethanol, a double phased picture of informational characteristics has been revealed in the cellular nuclei under a linear increase of the dose. An analysis of corresponding distribution of the hepatocytic nuclei has been performed according to their size and informational characteristics. On this base, the limiting dose of ethanol is estimated for development of the hepatic alcoholic lesion. PMID- 4040357 TI - Plasminogen activator activity levels in patients with Behcet's syndrome. AB - We studied the plasminogen activator levels in plasma samples of 37 patients with Behcet's syndrome. A significant decrease of plasminogen activator activity level was shown by the euglobulin lysis time method, the amidolytic activity level (Testzym method), and the fibrin plate method. Such a decrease may be associated with the severity of Behcet's syndrome. PMID- 4040358 TI - Perinatal outcome of induced labour. PMID- 4040359 TI - Diurnal variation in oxygen consumption of laboratory rats. AB - Oxygen consumption (VO2) was measured in Porton albino rats using a closed circuit apparatus. The groups studied were controls, cold-adapted animals, and those which had accumulated brown adipose tissue as a result of a cafeteria diet with a high energy content. It was possible to show in each group studied a difference in VO2 according to the time of day at which it was measured. This was consistent within each group studied. The diurnal variation shown (higher in the morning than in the afternoon) is characteristic of nocturnal animals. Measurement of VO2 then must be made within the same time-period or integrated over 24 h. Spurious correlations may otherwise occur. PMID- 4040360 TI - Characterisation of rat tumour cell hybrids: procoagulant and fibrinolytic activities. AB - The formation of lung colonies after i.v. injection of highly metastatic rat mammary adenocarcinoma cells (MAT 13762) was greatly reduced by concurrent treatment of rats with heparin. The procoagulant activity (PCA) of these cells, and of a non-metastatic adenocarcinoma (DMBA-8) has therefore been measured. These have been compared with PCA expressed by MAT 13762 cell derivatives including a non-metastatic hybrid clone (MAT 13762 X DMBA-8), its metastatic revertant, and clones selected in vivo from lung metastases. Potent PCA was expressed on intact MAT 13762 cells and in their spent culture media, the latter being sedimentable and associated with shed membrane vesicles. Cell-derived PCA, unlike thromboplastin, was equally effective in factor VII-deficient and normal bovine plasma. There were, however, no major differences in the expression of PCA (either cell-associated or shed) between the metastatic and non-metastatic cell types studied. Plasminogen activator (PA) production by these cells has also been measured. The results are discussed in the context of the possible role of fibrin formation and fibrinolysis in the metastatic process. PMID- 4040361 TI - Microbiology of chronic otitis media with effusion among Australian Aboriginal children: role of Chlamydia trachomatis. AB - Serum, eye secretions, post-nasal swabs, external ear swabs and middle ear effusions (MEE) were collected from 131 Australian Aboriginal children with chronic otitis media with effusion (COME). The children were all resident in a trachoma endemic region. Chlamydia trachomatis was recovered from the MEE of 2 children. Probable bacterial pathogens were isolated from 34 (12.7%) ears. The remainder were sterile (52.4%) or contained normal skin flora (34.9%). Serum and secretions were examined by the microimmunofluorescent technique for the presence, titre and serotype of anti-chlamydial antibody. Antibody, predominantly of the C serotype, was found in a high percentage of sera (80%) and secretions (approximately 50%). This serotype is associated with ocular trachoma. It is concluded that C. trachomatis is associated with COME among some Aboriginal children in this trachoma endemic area. PMID- 4040362 TI - The role of mechanistic data in dose-response modeling. AB - The results from employing metabolized dose in the case of vinyl chloride demonstrate that the delivered dose concept can radically alter the shape of the dose-response curve in the observable response range. Simultaneously, it can eliminate the obvious bias in low-dose risk estimates that arises from use of an inappropriate dose measure, namely, the administered airborne vinyl chloride concentration. For formaldehyde, the data regarding covalent binding to respiratory mucosal DNA provide the best measure of target tissue exposure that is currently available. The results obtained with this dose measure demonstrate that incorporation of the delivered dose concept into any of the commonly used low-dose extrapolation procedures leads to a unilateral reduction in estimated cancer risk associated with the exposure of rats to low airborne formaldehyde concentrations. These findings strongly suggest that low-dose risk estimates obtained with the administered formaldehyde dose as the measure of exposure are biased conservatively, and that regulatory assessments of formaldehyde should consider the delivered formaldehyde dose to be the valid and relevant measure of exposure. Additional research is, of course, required to refine and elaborate the delivered dose concept, especially for human exposures. Nevertheless, this concept provides a convenient vehicle for incorporating mechanistic information directly into the quantitative risk assessment process in a meaningful and relevant manner. Clearly, risk estimates based on delivered dose reflect what is known of the underlying biological reality more faithfully than estimates that are based solely on unverified assumptions and the findings in chronic bioassays. Use of the delivered dose concept should be strongly encouraged, since it can help place quantitative risk assessment on a sound and scientifically defensible footing. PMID- 4040364 TI - The production of 1,2-propanediol in ethanol treated rats. AB - Chronic administration of ethanol in the most commonly used experimental diet (Lieber, C. S., and DeCarli, L. M. (1976) Fed. Proceed. 35, 1232-1236) resulted in the production of 1,2-propanediol within one week of initiation of alcohol feeding. After two weeks 1,2-propanediol levels were 8.8 +/- 1.6 nmol/ml in alcohol treated animals. No 1,2-propanediol was apparent in pair fed control animals at any time during this study. Consistent with the proposed mechanism of production of 1,2-propanediol in acetone treated rats (Casazza, J. P., Felver, M. E., and Veech, R. L. (1984) J. Biol. Chem. 259, 231-236), both liver acetone and acetol monooxygenase activities and blood beta-hydroxybutyrate were elevated in ethanol treated animals. Acetone and acetol monooxygenase activities were 0.118 +/- 0.016 and 0.110 +/- 0.016 umol/min/g liver after two weeks of ethanol treatment. Acetone and acetol monooxygenase activities in pair fed controls were 0.016 +/- 0.002 and 0.015 +/- 0.002 umol/min/g liver. beta-Hydroxybutyrate levels were highest after one week of treatment; 1.64 +/- 0.12 umol/ml in ethanol treated rats and 0.16 +/- 0.02 umol/ml in pair fed controls. Throughout this study serum acetol and 2,3-butanediol were less than the detection limits of these assays (less than 5 nmol/ml). PMID- 4040363 TI - Distinct sites on the G-actin molecule bind group-specific component and deoxyribonuclease I. AB - Addition of group-specific component (Gc) to G-actin with or without deoxyribonuclease I (DNAase) led to formation of binary complexes (Gc-G-actin) and ternary complexes (Gc-G-actin-DNAase) respectively. The electrophoretic mobility of ternary complexes, as shown by crossed and rocket immunoelectrophoresis, was slower than that of binary complexes, although both were faster than native Gc. In gradient polyacrylamide-gel electrophoresis, such complexes could again be resolved, apparently on the basis of relative molecular size: Gc-G-actin-DNAase (Mr approx. 131000), Gc-G-actin (Mr approx. 98000) and Gc (Mr approx. 56000). In contrast, the pI of ternary complex was indistinguishable by isoelectric focusing from that of binary complex, even though both were clearly more acidic than native Gc. The affinity of Gc for G-actin (affinity constant, Ka, 1.9 X 10(8) M-1) was not significantly altered by additional interaction with DNAase (Ka, 1.5 X 10(8)M-1), and both binary and ternary complexes still bound 25-hydroxycholecalciferol. In addition, the inhibitory effect of G-actin on DNAase activity was not discernibly affected by interaction with Gc. These results demonstrate that the various molecular forms of Gc can be distinguished by physicochemical parameters, and that Gc and DNAase bind to distinct sites on G-actin and can interact both independently and contemporaneously with this molecule. PMID- 4040365 TI - Properties of a membrane-associated benzoate-4-hydroxylase from Rhodotorula graminis. AB - Membrane fractions of benzoate-induced Rhodotorula graminis hydroxylated benzoate in the para position as demonstrated by high-performance liquid chromatography and isotopic thin-layer chromatography. Benzoate-4-hydroxylase activity was linear as a function of enzyme concentration (washed membranes) and time, and exhibited a pH optimum of 7.6. The enzyme utilized NADPH as a source of reducing equivalents, and was stimulated by FAD. The Km's for benzoate and NADPH were calculated as approximately 2.9 X 10(-5) M and approximately -1.9 X 10(-5) M, respectively. The particulate nature of benzoate-4-hydroxylase together with the fact that the enzyme was pteridine-independent indicates that it is distinct from the isofunctional enzyme previously described in filamentous fungi. PMID- 4040366 TI - PTT.119, p-F-Phe-m-bis-(2-chloroethyl)amino-L-Phe-Met ethoxy HCl, a new chemotherapeutic agent active against drug-resistant tumor cell lines. AB - PTT.119 [p-F-Phe-m-bis-(2-chloroethyl)amino-L-Phe-Met ethoxy HCl], a new synthetic tripeptide, was highly effective against the L-phenylalanine mustard (L PAM) resistant (L1210/L-PAM and P388/L-PAM) tumor lines, as well as the sensitive L1210 leukemia. Cytolytic activity of PTT.119 against all three leukemias was significantly greater than equimolar doses of L-PAM. These in vitro results paralleled the significant increases in mean survival times of hosts and, in some cases, abrogations of tumor formation observed in the in vivo bioassays of PTT.119-treated L1210 and L1210/L-PAM cells. Dose-response studies failed to demonstrate cross-resistance to the tripeptide by L-PAM resistant cells. Doses of PTT.119 required to reduce the viable fraction by 50% (tissue culture dose 50, TCD50) or 100% (TCD100) were 1.3- to 3-fold lower for the L-PAM resistant cells than for the L1210 leukemia. In comparison, L-PAM was unable to completely eliminate cell survival; 0.2 to 3% of the cells in all three leukemias remained viable even at doses of 75 and 163 microM. In similar studies, L1210 leukemia cells made resistant to methotrexate (L1210 MTX) and cisplatin (L1210DDP) were also completely susceptible to PTT.119; TCD50 values of the two resistant lines were 1.94 microM for L1210 MTX and 0.525 microM for L1210DDP compared to 2.38 microM for the susceptible parent L1210S leukemia. Continuous low-dose PTT.119 treatment of MJY-alpha mammary tumor cells for 8 months and exposure of L1210 leukemia to escalating levels of tripeptide for over 100 passages failed to select or induce drug-resistant phenotypes in either cell line. PTT.119 appears to be a poor mutagen and is unlikely to readily increase the probability of drug resistant mutants in the tumor cell populations. PMID- 4040367 TI - A study of the protective effect of chloride salts on cisplatin nephrotoxicity. AB - In rats NaCl and NH4Cl (25 mmoles/kg, p.o.) were found to be equally effective at preventing nephrotoxicity when administered to rats 90 min before cisplatin (5 mg/kg i.p.) but (NH4)2SO4 did not protect. The severity of nephrotoxicity, taken as the maximum elevation in blood urea concentration, showed a high degree of correlation with urinary chloride concentration, but not with urinary pH or volume. Sodium chloride did not protect against nephrotoxicity when administered 3 or 24 hr after cisplatin. Sodium chloride showed protection against nephrotoxicity caused by cisplatin metabolites only at low doses of platinum. For animals pretreated with NaCl (25 mmoles/kg) or water p.o. the urinary excretion of total platinum, cisplatin and six of the seven metabolites separated by hplc was not significantly different between the two treatments during the 0-5-hr period post dosing. However, one metabolite, possibly a nephrotoxic hydrolysis product, was excreted in significantly smaller amounts in the urine of animals pretreated with NaCl (P less than 0.05). Furthermore, in all cisplatin treated animals the amount of this species excreted correlated with the severity of nephrotoxicity. Whilst this suggests that chloride ions may protect against the nephrotoxicity of cisplatin by inhibiting its rate of metabolism this metabolite accounts for only 2.5% of the platinum excreted. Furthermore, the data do not exclude the possibility that NaCl prevents cisplatin-induced nephrotoxicity by preventing renal ischaemia, which may normally follow cisplatin treatment, or that the renal uptake or transport of platinum may be inhibited by NaCl. PMID- 4040368 TI - Cisplatin-induced alteration of the copper and zinc content of the rat kidney. PMID- 4040369 TI - Augmentation of adriamycin, melphalan, and cisplatin cytotoxicity in drug resistant and -sensitive human ovarian carcinoma cell lines by buthionine sulfoximine mediated glutathione depletion. PMID- 4040370 TI - Chronic treatment with clozapine, unlike haloperidol, does not induce changes in striatal D-2 receptor function in the rat. AB - Comparison has been made of the effects on brain dopamine function of chronic administration of haloperidol or clozapine to rats for up to 12 months. In rats treated for 1-12 months with haloperidol (1.4-1.6 mg/kg/day), purposeless chewing jaw movements emerged. These movements were only observed after 12 months' treatment with clozapine (24-27 mg/kg/day). Apomorphine-induced (0.125-0.25 mg/kg) stereotyped behaviour was inhibited during 12 months treatment with haloperidol. Clozapine treatment was without effect. After 12 months, stereotypy induced by higher doses of apomorphine (0.5-1.0 mg/kg) was enhanced in haloperidol, but not clozapine, treated rats. Bmax for striatal 3H-spiperone binding was elevated throughout 12 months of haloperidol administration, but was not altered by clozapine treatment. Bmax for striatal 3H-NPA binding was only elevated after 12 months of haloperidol treatment; clozapine treatment was without effect. Bmax for 3H-piflutixol binding was not altered by haloperidol treatment, but was increased after 9 and 12 months of clozapine treatment. Dopamine (50 microM)-stimulated adenylate cyclase activity was inhibited after 1 month's haloperidol treatment but normal thereafter. Adenylate cyclase activity was not altered by chronic clozapine treatment. Striatal acetylcholine content was increased after 3 and 12 months of haloperidol or clozapine intake. These findings indicate that the chronic administration of the atypical neuroleptic clozapine does not produce changes in brain dopamine function which mirror those of the typical neuroleptic haloperidol. In particular, chronic administration of clozapine, unlike haloperidol, does not appear to induce striatal D-2 receptor supersensitivity. Unexpectedly, clozapine treatment, unlike haloperidol, altered D-1 receptor function. PMID- 4040371 TI - Serum high density lipoprotein subclasses, testosterone and sex-hormone-binding globulin in Trinidadian men of African and Indian descent. AB - Serum high-density lipoprotein (HDL) cholesterol, testosterone and sex-hormone binding globulin (SHBG) were measured in 300 men, aged 35-64 years, of African and Indian descent who represented a 40% sample of participants in a community survey of coronary heart disease in Trinidad. Free testosterone was calculated from total testosterone and SHBG. In 113 men, HDL2 and HDL3 cholesterol were measured by a precipitation technique. Indian men had a significantly lower HDL cholesterol concentration than African men (P = 0.003), which is known to be due to a reduction in the HDL3 fraction (demonstrable only in younger men in the subsample drawn for this study). Testosterone did not differ with ethnic group, but SHBG was reduced in Indians (P = 0.03). After allowance for age, ethnic group, alcohol consumption and smoking habit, HDL cholesterol was associated positively with SHBG (P = 0.025) but was not related significantly to either total testosterone or its free and bound components. Serum HDL2 cholesterol was associated positively and independently with SHBG (P = 0.001) and total and bound testosterone (P = 0.002), whereas HDL3 cholesterol showed no significant associations with these factors. Neither SHBG or testosterone afforded an explanation for the relatively low HDL and HDL3 cholesterol concentrations in Indian men. PMID- 4040372 TI - Discrepancy between the different subcellular activities of rat liver catalase and superoxide dismutases in response to acute ethanol administration. AB - After acute ethanol administration (2.3 g/kg) peroxisomal and extra-peroxisomal catalase activities were affected in opposite directions. As long as ethanol was present, peroxisomal catalase activity was enhanced, but unaffected by amino triazole (AT) injection. Extra-peroxisomal catalase activity was decreased during the 24hr following ethanol administration and was also inhibited after AT injection. Whereas mitochondrial manganese-dependent superoxide dismutase (Mn SOD) was unaffected, the cytosolic Cu,Zn-SOD activity was decreased. The time course of this decrease suggests that acute ethanol administration affects primarily extra-peroxisomal catalase activity, thus rendering cytosolic superoxide dismutase more exposed to oxygen derivatives. PMID- 4040373 TI - Effect of retinoic acid (RA) and retinyl palmitate (RP) repletion on lymphocytes of vitamin A deficient rats. PMID- 4040374 TI - [The XX male syndrome]. PMID- 4040375 TI - Catalase mediated conversion of cyanamide to an inhibitor of aldehyde dehydrogenase. AB - A minor pathway for cyanamide metabolism catalyzed by catalase is responsible for the conversion of cyanamide to an inhibitor of aldehyde dehydrogenase. Catalase itself is also inhibited by cyanamide. Both the activation of cyanamide by catalase and the inhibition of catalase by cyanamide were blocked in vivo by ethanol pretreatment, suggesting that these two processes are closely linked. Like other catalase oxidation reactions, the catalase mediated activation of cyanamide was inhibited by 3-amino-1,2,4-triazole in vivo and sodium azide in vitro. The relative formation of the active cyanamide metabolite was assessed in vitro by following the loss of yeast aldehyde dehydrogenase activity with time. Inhibition of the yeast enzyme by activated cyanamide was dependent on NAD+ or NADP+, a requirement not fulfilled by NADH or NADPH. Although H2O2 inhibited yeast aldehyde dehydrogenase in vitro and cyanamide inhibited hepatic catalase in vivo, the possible in hepatic H2O2 concentration following cyanamide administration does not account for the effects of cyanamide on ethanol metabolism. While the cyanamide activating enzyme has been identified as catalase, the reaction products of this reaction and, in particular, the structure of the active metabolite involved in the inhibition of aldehyde dehydrogenase remain unknown. PMID- 4040376 TI - Effects of ethanol on the rat brain: ultrastructural alterations in the temporal cortex and in the hippocampus. AB - Male rats were submitted either to an oral alcohol intoxication or to chronological aging. Nervous morphometry shows that chronic alcohol consumption induces an increase in the proportion of neurons with dense cytoplasm and an increase of the synaptic cleft affecting principally synapses with spherical vesicles. The cerebrovascular morphometry revealed that the vascularity enhances with chronic alcohol consumption in young animal. The same enhancement is observed in aged animals showing thus a parallelism between alcoholised and aged animals. PMID- 4040377 TI - Acetaldehyde and alcohol levels in pregnant rats and their fetuses. AB - Alcohol and acetaldehyde blood levels were measured in chronic alcoholic pregnant rats and their fetuses at 15, 19 and 21 days of gestation. Similar ethanol concentrations were found in fetal and maternal blood in all gestation periods studied, however levels in amniotic fluid were higher than in mother's blood, especially in the early stages of gestation. Acetaldehyde concentrations were always lower in fetal than in maternal blood although increasing throughout gestation. The levels in fetal blood and amniotic fluid compared to maternal blood, were ca. 40, 50 and 70% at 15, 19 and 21 days of gestation, respectively; those for the placenta and fetal tissues were lower, i.e., 25, 40 and 50%. Similar alcohol and acetaldehyde ratios (fetus/mother's concentration) were obtained when pregnant non-alcoholic rats were administered cyanamide and ethanol (2 g/kg) at 11, 15, 19 and 21 days of gestation. These results demonstrate that ethanol freely crosses the placental barrier, but there is a concentration gradient of acetaldehyde between mother and fetus which varies with gestation age. PMID- 4040378 TI - Delayed taste aversion learning in preweanling rats exposed to alcohol prenatally. AB - Parallels between the behavioral profiles of rats exposed to alcohol prenatally and those with hippocampal damage suggest that hippocampal dysfunction may underlie some of the behavioral abnormalities resulting from prenatal alcohol exposure. Because of possible hippocampal involvement in the acquisition of a delayed conditioned taste aversion, this task was assessed in rat pups exposed to alcohol prenatally. Long-Evans rats were maintained on liquid diets containing either 35% or 0% ethanol derived calories from Days 6-20 of gestation. Pair feeding procedures and an ad lib Lab Chow (LC) group were included. Fifteen-day old offspring from these three groups were given access to saccharin and then injected immediately (0 hr) or 2 hr later with either lithium chloride (LiCl) or sodium chloride (NaCl). Immediate pairing of saccharin with LiCl produced a marked taste aversion, although this effect was less pronounced in 35% EDC pups. In the 2 hr condition, weaker aversions were exhibited and again the 35% EDC group showed the least aversion. However, prenatal treatment did not interact with the injection interval. PMID- 4040379 TI - Negative chronotropic effect of chronic ethanol ingestion in the rat. AB - The chronic consumption of ethanol has been correlated with the development of arrhythmias. This study looked at the effect of chronic ethanol ingestion on the action potential of sino-atrial cells. The studies were carried out on hearts excised from male Long-Evans hooded rats, pair-fed on ethanol (E) or control (C) liquid diet. The ethanol diet supplied 35-39% of calories as ethanol. The studies of isolated sino-atrial tissue were carried out after 18-20 weeks, 30-32 weeks and 40-42 weeks on the diet. Sino-atrial cells from E and C rats were compared for changes in spontaneous rate, action potential amplitude, time to repolarize to -70 mV, and resting membrane potential. At 18-20, 30-32 and 40-42 weeks the spontaneous rate of firing of the sinus node was significantly lower in the E group as was the maximum response to isoproterenol. The time to repolarize to -70 mV was longer in E. The endogenous level of catecholamines was also lower in the E group. PMID- 4040380 TI - Oral self administration of ethanol in free feeding rats. AB - The use of animal models to study factors involved in excessive alcohol intake has prompted a number of investigators to propose criteria for an optimal model. One of these criterion, oral ingestion of intoxicating amounts of ethanol without concomitant weight loss and/or food restriction, has proven difficult to fulfill, especially when using rats. The following study reports a conditioning paradigm which was used to establish oral ethanol self administration in free feeding rats. Through initial reinforcement of 5% (v/v) ethanol consumption with 20% (w/v) sucrose solution, rats were trained to work for and consume concentrations of ethanol up to and including 40%. Blood ethanol levels above 100 mg ethanol/dl blood were frequently found. A control group, induced to drink quinine with the same procedures, indicated the relative importance of ethanol's pharmacological effect in maintaining high levels of self administration. The results show ethanol can maintain oral self administration of intoxicating quantities of high ethanol concentrations in free feeding rats, when its initial consumption is paired with an additional reinforcer. PMID- 4040381 TI - Norepinephrine turnover and voluntary consumption of ethanol in the rat. AB - The effect of a centrally acting noradrenergic agonist on voluntary ethanol intake was investigated in the laboratory rat. Doses of 1.5, 7.5, 15 and 25 mg/kg of FLA-136 were administered to animals chronically exposed to ethanol on a free choice basis. Administration of the highest dose of the drug brought about a 40% reduction in voluntary ethanol intake with no significant effect on total fluid consumption. These results would seem to indicate a possible functional relationship between rate of norepinephrine turnover and amounts of ethanol voluntarily consumed by the laboratory rat. PMID- 4040382 TI - A two dimensional model of alcohol consumption: possible interaction of brain catalase and aldehyde dehydrogenase. AB - The possible existence of a biological marker system mediating voluntary consumption of ethanol in rats has been examined in a series of studies. The working hypothesis underlying this research was that acetaldehyde, the primary metabolite of ethanol, mediates the positive reinforcing properties of ethanol and thus underlies the voluntary consumption of ethanol in both animals and humans. We further hypothesized that brain catalase and aldehyde dehydrogenase, the enzymes controlling the production and elimination of acetaldehyde in the brain, may represent a biological marker system underlying the affinity of the animals to consume ethanol. Data demonstrating that the activity levels of these enzymes are positively correlated with alcohol ingestion seems to suggest that it is likely that the enzyme activity can serve as a predictor of the propensity to drink alcohol. A predictive model is proposed which describes the modulation of voluntary ethanol intake through the activity of these enzymes and their role in determining rates of formation and degradation of acetaldehyde in the brain. PMID- 4040383 TI - Retinal changes in myotonic dystrophy: a clinicomorphological study. AB - This report appears to be the first ultrastructural study of the maculopathy and peripheral pigmentary retinopathy in myotonic dystrophy. Nine eyes from five patients observed during life are described. The findings were similar in all eyes, the retinal pigment epithelium in the macular region containing an accumulation of lipofuscin in large hyperpigmented cells. Pigment-laden profiles found in the subpigment epithelial space or subretinal space were interpreted as an attempt to discharge the pigment. Stress fibres of actin microfilaments were thrown into prominence by the irregularity of the pigment epithelium. In the periphery migration of retinal pigment cells into the retina occasionally resulted in the formation of bone corpuscles around occluded vessels, as occurs in retinitis pigmentosa; but more often the clumps were coarser and surrounded basement membrane material. Central and peripheral epiretinal membranes were also observed. PMID- 4040384 TI - Left ventricular gradients in hypertrophic cardiomyopathy. PMID- 4040385 TI - Asthma and allergic aspergillosis in monozygotic twins. AB - Monozygotic twins are reported; both had bronchial asthma with type I hypersensitivity to Aspergillus fumigatus but only one had type III hypersensitivity, together with pulmonary infiltrations compatible with the diagnosis of allergic bronchopulmonary aspergillosis. It is suggested that non inherited factors other than the intensity of exposure to antigen may be important in determining the development of allergic bronchopulmonary aspergillosis. PMID- 4040386 TI - Investigation and treatment of orogenital ulceration; studies on a possible mode of action of thalidomide. PMID- 4040387 TI - Solvent neurotoxicity. PMID- 4040388 TI - Silastic sling for urethral sphincter incompetence in women. AB - Conventional sling materials have numerous disadvantages. A reinforced Silastic sling is described and its use reported in 30 patients. There was an 83% symptomatic and objective cure of stress incontinence. The advantages of this material include its consistent strength, adjustability and ease of removal. PMID- 4040389 TI - Combination chemotherapy of ovarian carcinoma with cisplatinum and treosulfan--a phase II study. AB - Twenty-one patients with advanced ovarian carcinoma were treated with a combination of cisplatinum and treosulfan. The overall response rate by clinical and ultrasound assessment was 86%, but ultrasound was less optimistic in assessing 'completeness' of response (48% compared with 67% clinically). The median actuarial survival was 21 months. There was a 54.9% probability of survival at 43 months in those patients with a complete response and a median survival of 15 months in patients with a partial response. The data suggest that while short-term survival may depend upon the extent of residual disease, longer term survival is determined by response to chemotherapy. The only toxicity of note was haematological. PMID- 4040390 TI - Location of the maltosyl isothiocyanate binding site on the human erythrocyte glucose transporter. AB - The covalent affinity probe maltosyl isothiocyanate (MITC) has been used previously to identify the glucose transporter of human erythrocytes as a component of band 3. By use of limited proteolysis, the site on the Mr 100 000 protein to which MITC attaches has been localized to a 17 000-dalton region near the center of the polypeptide chain which is intimately associated with the membrane. The erythrocyte anion transporter, which is probably homologous to the glucose carrier, has a corresponding segment which is known to bind the covalent affinity label 4,4'-diisothiocyano-2,2'-stilbenedisulfonic acid [Ramjeesingh, M., Gaarn, A., & Rothstein, A. (1980) Biochim. Biophys. Acta 559, 127-139]. These results suggest that, in addition to having structural features in common, the two carrier proteins may be quite similar with regard to functional organization. PMID- 4040391 TI - Effects of bilayer cholesterol on human erythrocyte hexose transport protein activity in synthetic lecithin bilayers. AB - In this study, we describe the effects of altered bilayer cholesterol content on reconstituted, protein-mediated sugar transport. The system used was the human erythrocyte sugar transporter (band 4.5) reconstituted into the bilayers of large unilamellar vesicles. Vesicle preparations were formed from synthetic lecithins whose bilayer cholesterol content ranged from 0 to 50 mol %. Transport was measured by microturbidimetric analysis over the temperature range of 0-65 degrees C while bilayer physical state was characterized by differential scanning calorimetry. Reconstituted transport activity was irreversibly lost between 62 and 65 degrees C. The Km for reconstituted transport was found to increase only slightly with increasing temperature and was not systematically affected by bilayer cholesterol content. The most striking observation of this study is that over certain critical cholesterol concentrations, as little as a 2.5% change in bilayer cholesterol can result in as much as a 100-fold change in Vmax per reconstituted protein. Our findings run counter to the view that increasing bilayer cholesterol content monotonically transforms a membrane into a state of "intermediate fluidity". Abrupt, cholesterol-induced bilayer reorganizations occurring at 15-20 and 30 mol % bilayer cholesterol are markedly reflected in altered sugar transport rates. Increasing the cholesterol content of crystalline distearoyllecithin bilayers inhibits the activity of the reconstituted transporter. It is apparent from these studies that bilayer "fluidity" is neither the sole nor a major determinant of the Indeed, we find the effect of cholesterol on transport activity is independent of its ability to fluidize membranes. PMID- 4040392 TI - Structure-function correlation of fatty acyl-CoA dehydrogenase and fatty acyl-CoA oxidase. AB - We have employed a new pseudosubstrate, beta-(2-furyl)propionyl coenzyme A (FPCoA), to study the functional properties of two enzymes, fatty acyl-CoA dehydrogenase from porcine liver and fatty acyl-CoA oxidase from Candida tropicalis, involved in the oxidation of fatty acids. Previous studies from our laboratory have shown that the dehydrogenase exhibits oxidase activity at the rate of dissociation of the product charge-transfer complex. This raises the question of the difference in functionality between these two flavoproteins. To investigate these differences, we have compared the pH dependence of product formation, the isotope effects using tetradeuterio-FPCoA, and the spectral properties and chemical reactivity of the product charge-transfer complexes formed with the two enzymes. The pH dependencies of the reaction of FPCoA with electron-transfer flavoprotein (ETF) for the dehydrogenase and of the reaction of FPCoA with O2 for the oxidase are quite similar. Both reactions proceed more rapidly at basic pH values while substrate binds more tightly at acidic pH values. These data for both enzymes are consistent with a mechanism in which enzyme is involved in protonation of the carbonyl group of substrate followed by base-catalyzed removal of the C-2 proton from substrate. The C-2 anion of substrate may then serve as the active species in reduction of enzyme-bound flavin. The deuterium isotope effects for both enzyme systems are primary across the entire pH range, assuring that the chemically important step of substrate oxidation is rate limiting in these steady-state kinetic experiments. The two enzymes differ in the chemical reactivity of their product charge-transfer complexes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4040393 TI - Reconstitution of the glucose transport activity of rat adipocytes. AB - Rat epididymal fat cell membrane proteins were extracted from adipocyte ghosts with octylglucoside and incorporated by detergent dialysis into unilamellar phosphatidylcholine vesicles approx. 200 nm in diameter. The rate of glucose transport into the vesicles under zero-trans conditions was substrate dependent, saturable and inhibited by phloretin and cytochalasin B. Their maximum specific transport activity was 35.6 mumol/min per mg protein, and their half saturation constant for glucose was 15 mM. Glucose transport into the reconstituted vesicles was inhibited by only those sugars which competitively inhibited glucose transport into intact adipocytes. A major protein component of the vesicles was a 100 kDa protein which we had previously found to react with the affinity label maltosyl isothiocyanate (Malchoff, D.M., Olansky, L., Pohl, S. and Langdon, R.G. (1981) Fed. Proc. 40, 1893). Removal of adipocyte ghost membrane extrinsic proteins with dimethylmaleic anhydride followed by extraction of the resulting membrane pellet with octylglucoside yielded a solution which contained two major proteins, of Mr 100 000 and 85 000, with very small quantities of lower Mr proteins. Vesicles into which these proteins were incorporated had average specific transport activities of 624 mumol/min per mg protein and half saturation constants of 22 mM. Our results strongly indicate that the native glucose transporter of the rat adipocyte, like that of the human erythrocyte (Shelton, R.L. and Langdon, R.G. (1983) Biochim. Biophys. Acta 733, 25-33), is a 100 kDa protein. PMID- 4040394 TI - Specific recognition by the tripeptide lysyl-tryptophyl-alpha-lysine of structural damage induced in DNA by platinum derivatives. AB - The antitumoral derivative cisPt binds to DNA, as do its inactive analogs, trans- and dienPt. Structural damage introduced into DNA after reaction with the Pt derivatives were probed by using the peptide LysTrpLys. This peptide was used for its preferential binding to single-stranded structures (Brun, F., Toulme, J.J. and Helene, C. (1975) Biochemistry 14, 558-563). Phosphorescence lifetime measurements show that the Pt-induced heavy atom effects are quite similar in the three peptide-DNA-Pt complexes whatever the nature of the Pt derivative used. In contrast, fluorescence quenching strongly depends on the nature of the Pt derivatives. This quenching was therefore attributed to the stacking interactions engaged by the tryptophan residue with nucleic acid bases. A comparison of fluorescence quenching data for native and modified DNAs demonstrates that modification by dienPt has no effect on stacking interactions and that high levels of modifications by trans Pt are required to observe a change in stacking efficiency. In contrast modification by cis Pt induces the formation of strong stacking sites. The results strongly suggest the existence of locally opened regions in DNA modified by cis Pt. PMID- 4040395 TI - An electro-optical study of the mechanisms of DNA condensation induced by spermine. AB - Condensation of DNA by spermine has been studied by electric dichroism, electric birefringence and rotational relaxation times at 1 mM ionic strength. Using Manning's theory, we found that condensation occurs for a fraction of neutralized phosphate charges (r) equal to 0.90, in good agreement with previous studies using spermidine, synthetic polyamines and trivalent cations (e.g. Co(NH3)36 +, Tb3 +). Our results are compatible with the presence in solution of torus-shaped condensed structures in a narrow range of spermine concentration; further addition of the polyamine produced precipitation due to the self-aggregation of several toroids. For spermine concentrations lower than that required for collapse, important changes of the orientation mechanism in the electric field and of DNA stiffness were observed. Whereas free DNA was mainly oriented by a fast-induced polarizability mechanism, DNA-spermine complexes displayed an important permanent dipole component, in the spermine concentration range where extension of the DNA molecules was present. The birefringence relaxation times suggested that, in the first step, the stiffness of the DNA molecules increased, and then, at higher spermine concentration, bending of the DNA molecules occurred so that condensation into toroidal particles became possible. PMID- 4040396 TI - Large-scale purification of human tissue-type plasminogen activator using monoclonal antibodies. AB - Tissue plasminogen activator produced by a human melanoma cell line (Bowes), was purified from large volumes of supernatant fluid using immunosorbent chromatography on monoclonal antibodies, followed by chromatography on lysine Sepharose 4B and gel filtration on Sephadex G-150. Immunosorbents based on monoclonal antibodies were shown to be preferable to those based on polyclonal antibodies for several reasons: efficient binding and desorption, high yield along with a high degree of purification. The overall recovery was about 50%. A homogeneous sample of single-chain tissue plasminogen activator with a molecular weight of approx. 65 000 was obtained as judged by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulphate. Amino acid sequence analysis revealed two N-terminals in equal yields, corresponding to the long and short tissue plasminogen activator structures previously reported by others. The pure preparations of tissue plasminogen activator showed specific activities of about 200 000 IU/mg protein. PMID- 4040397 TI - Isoenzymes of vitamin-K-dependent carboxylase. AB - Vitamin-K-dependent carboxylase was prepared from bovine liver, kidney, lung and testis and it was checked that these systems obeyed the laws of normal enzyme kinetics. Four carboxylatable substrates were obtained from different sources and the apparent Michaelis constants of the various carboxylases for these four substrates were measured. From the results thus obtained we concluded that carboxylase is a group name for a number of isoenzymes which are present in hepatic as well as in various non-hepatic tissues. PMID- 4040398 TI - Blood group B-specific lectin of Plecoglossus altivelis (Ayu fish) eggs. AB - A lectin that agglutinates human blood group B erythrocytes but not blood group A and O erythrocytes was isolated from eggs of Ayu sweet fish (Plecoglossus altivelis). The lectin also agglutinates Ehrlich ascites carcinoma cells but not rat ascites hepatoma AH109 or rat sarcoma 150 cells tested. The lectin agglutination was most effectively inhibited by monosaccharides with the first type of configuration, i.e., L-rhamnose, L-mannose and L-lyxose at a concentration of 0.03 mM. The lectin agglutination was moderately inhibited by monosaccharides with the second type of configuration, i.e., D-galactose, D fucose and D-galacturonic acid at a concentration of 0.4 mM. However, the agglutination was not inhibited by various other monosaccharides and oligosaccharides that have other types of configuration. The basis for an apparent B-specific hemagglutination may be due to the steric similarity of the C2 and C4 of the galactosyl series, the B-specific determinant, and the L rhamnosyl-Sepharose column and was characterized as a homogeneous low molecular weight protein (Mr 14000) with an abundance of hydrophobic amino acids and dicarboxylic amino acid. PMID- 4040399 TI - In vivo induction of rat hepatic ornithine decarboxylase and plasminogen activator by 12-O-tetradecanoylphorbol 13-acetate. AB - Rapid and substantial elevations in ornithine decarboxylase and plasminogen activator have been linked to tumor promotion in mouse epidermis and in vitro. Systemic administration of 12-O-tetradecanoylphorbol 13-acetate (TPA) rapidly increased both enzymic activities in rat liver. Pretreatment with either cycloheximide or actinomycin D attenuated both enzyme inductions. It is concluded that: (1) systemic TPA rapidly induces plasminogen activator and ornithine decarboxylase activities in rat liver; and (2) both inductions reflect de novo enzyme synthesis. PMID- 4040400 TI - Delayed anovulatory syndrome induced by estradiol in female C57BL/6J mice: age like neuroendocrine, but not ovarian, impairments. AB - These studies describe induction of a delayed anovulatory syndrome (DAS) by estradiol (E2) in female C57BL/6J mice. Six days after birth, female mice were injected s.c. with 0.1 micrograms estradiol benzoate or oil. Over 90% of the oil injected controls exhibited estrous cycles from 2 to 9 mo of age. In contrast, 60% of the E2-injected mice exhibited estrous cycles at 2 mo of age but were acyclic by 9 mo; these mice were considered to have exhibited a DAS, and had longer cycles than controls. At 12 mo, ovarian impairments were assessed by examining 1) ovulation after s.c. injection of 5 IU human chorionic gonadotropin (hCG), and 2) estrous cycles after grafting into young (3-mo-old) hosts. Simultaneously, neuroendocrine impairments were assessed by examining 1) the surge of luteinizing hormone (LH) induced by E2 implants after ovariectomy, and 2) estrous cycles after receiving ovarian grafts from 3-mo-old mice. Ovaries from DAS and control mice ovulated equally in response to hCG. Ovaries from DAS mice grafted into young ovariectomized hosts supported 30% more cycles, of shorter period, compared with ovaries from control donors. However, the E2-induced LH surge was 50% smaller in DAS mice than in controls. Ovariectomized DAS hosts with ovarian grafts from young mice supported 70% fewer estrous cycles, of longer period, compared with ovariectomized control hosts with young grafts. We conclude that the E2-induced DAS in female mice is not due to ovarian impairments, but seems to result from neuroendocrine impairments. PMID- 4040401 TI - Prenatal effects on reproductive capacity during aging in female mice. AB - The production of live young during successive pregnancies was investigated in female CF-1 house mice (Mus musculus) identified at cesarean delivery as having developed in utero between 2 male fetuses (2M females) or not next to a male fetus (0M females). 2M female mice have previously been found to be exposed to higher concentrations of testosterone than 0M females during fetal life, presumably as a result of the transport of steroids between contiguous fetuses. 0M and 2M females were paired with stud males. The males were removed prior to delivery of a litter and replaced by other males when the litter was weaned. This process was repeated until: 1) a female did not become pregnant within 2.5 mo or 2) two successive litters were produced in which all of the pups were dead. In Experiment 1 females were first mated when 25 days old, and 2M females ceased producing litters containing live pups at a younger age and after fewer litters than did 0M females; however, many females were terminated from the study as a result of producing 2 successive litters of dead young rather than failing to become pregnant during a 2.5-mo period. There was a gradual decline in the number of live young produced by 0M females as a function of age and parity, but 2M females abruptly ceased producing any live young after producing a litter of normal size. For the last live litter, there were thus significantly fewer live young produced by 0M females than by 2M females. None of these differences were observed in Experiment 2, in which 0M and 2M females were mated for the first time beginning at 7 mo of age. The 2M females in this experiment ceased producing live young at a significantly older age than did the 2M females first mated at puberty. In contrast, there was no effect of age at initial mating on the age at which 0M females ceased producing live young. This finding suggests that exposure of 2M females to elevated titers of testosterone during fetal life results in a reduction in reproductive life span if they first become pregnant during the pubertal period. PMID- 4040402 TI - The glycocalyx of the mouse uterine luminal epithelium during estrus, early pregnancy, the peri-implantation period, and delayed implantation. I. Acquisition of Ricinus communis I binding sites during pregnancy. AB - Mouse uteri were examined during estrus, early pregnancy, the peri-implantation period, and delayed implantation to determine whether changes in the surface coat of the luminal epithelium could be associated with receptivity of the uterus to the presence of blastocyst-stage embryos or blastocyst adhesion. By using alkaline bismuth subnitrate to label periodate-oxidized glycols within the glycocalyx we were able to measure the thickness and examine the morphology of the glycocalyx by electron microscopy. Ferritin-conjugated Ricinus communis agglutinin (RCA-I) demonstrated the presence of D-galactose at terminal, nonreducing positions within the glycocalyx. A relatively thick (0.06-0.1-micron) surface coat was present during estrus, but contained almost no RCA-I binding sites. During Day 3 of pregnancy the surface coat remained up to 0.1 micron thick and RCA-I binding sites were present. At Day 4 and during delay the glycocalyx had a fibrillar appearance, contained RCA-I binding sites, and was reduced to 0.06-0.08 micron in thickness. During Day 5 of pregnancy the thickness of the surface coat was greatly reduced, but there remained uniform lectin binding adjacent to the plasma membrane both at sites of blastocyst attachment and between implantation sites. The results indicate that the luminal epithelium of the mouse uterus acquired RCA-I binding sites during pregnancy and that the thickness of the surface coat was greatly reduced at the time of implantation. PMID- 4040403 TI - [Effect of chronic emotional stress on lipid peroxidation in the tissues and blood of emotional and nonemotional rats]. AB - The effect of chronic emotional stress on lipid peroxidation (LP) in tissues and blood was studied in "emotional" and "nonemotional" rats. In was established that the content of LP products in the brain, liver and myocardium, the blood content of beta- and pre-beta-lipoprotein hydroperoxides, and peroxide resistance of red blood cells were higher in "emotional" than in "nonemotional" animals. The stress induced increase in the individual differences as regards LP correlates with the intensity of the pathological somatic manifestations. PMID- 4040404 TI - [Mechanism of the intensification of the immune response to Staphylococcus in mice after the transplantation of primed donor splenocytes]. AB - Experiments on CBA, C57Bl/6 mice and (CBA X X C57Bl/6)F1 hybrids were made to study the mechanism of stimulation of the immune response to staphylococci after injection of primed splenocytes. The stimulating action of immune splenocytes was reversed after their in-vitro treatment with anti-immunoglobulin serum and complement. The stimulant effect was also seen in a semi-allogeneic system (adoptive transfer of CBA mice immune cells to (CBA X C57Bl/6)F1 recipients). Preincubation of splenocytes with CBA-anti-C57Bl/6-serum and complement prior to demonstration of antibody-forming cells did not influence their number in the spleen of hybrid recipients injected with immune cells carrying parent genotype but decreased this indicator of the immune response in control mice. It is concluded that stimulation of the immune response to staphylococci after transplantation of primed splenocytes is due to the anamnestic response of donor's cells repeatedly stimulated by antigen in the recipient's host. PMID- 4040405 TI - [Strains of human gastrointestinal and uterine tumors transplantable into athymic mice and rats]. AB - The authors describe strains of human cancer of the stomach, colon, cervix and corpus uteri as well as uterine chorionepitheliomas transplanted into nude mice and rats. The histological appearance of these strains is in full accordance with that of primary tumors. Electrophoresis of lactate dehydrogenase isozymes indicates that the strains mainly consist of human cells. The strains are transplanted in nude animals at various time intervals. The strains of human gastric cancer are transplanted from animal to animal in a month and those of corpus uteri in a week. PMID- 4040407 TI - [Effect of ionol on the stomach lesion in rats during immobilization stress]. AB - Intragastric administration of the antioxidant ionol (50 mg/kg/a day) for 7 days did not prevent the formation of ulcers or massive hemorrhages to the gastric mucosa in immobilized animals, increased the number of petechiae and lowered that of erosions. In this case the parietal pH increased in the stomach and dropped in the remaining divisions of the alimentary tract. The combined action of stress and ionol brought about marked hypocoagulation. Ionol exerted a protective action on the stress-induced activation of lipid peroxidation in the stomach but did not produce any such effect on the liver. PMID- 4040406 TI - [Prevention of the stress-induced decrease in natural killer activity by using a beta-adrenergic blocker and vitamin E]. AB - The data are provided on the efficacy of the use of the beta-adrenoblocker inderal and the natural antioxidant vitamin E as agents that prevent the immobilization stress-induced depression of the activity of natural killers. The problems of the prevention of the action of excess catecholamines and activation of lipid peroxidation as pathogenetic component in the development of stressor depression of the activity of natural killers are discussed. PMID- 4040408 TI - [Prevention of disorders in the contractile function of the nonischemic portion of the heart during infarction by preliminary adaptation to brief stress exposures]. AB - Preliminary adaptation to short-term exposures to immobilization stress prevents to a large extent the depression of contractile function and the lowering of the right atrium myocardium resistance to hypoxia and excess Ca2+ in experimental infarction of the left ventricle. This fact agrees with the concept that disturbance occurring in the nonischemic heart during infarction is caused by stress-induced damage. PMID- 4040409 TI - Drug-dependent and non-drug-dependent antiplatelet antibody in drug-induced immunologic thrombocytopenic purpura. AB - The mechanism of drug-dependent immunologic thrombocytopenic purpura (DITP) was investigated by studying the sera of four patients with classic DITP (two with quinidine-, one with acetaminophen-, and one with phenazopyridine-dependent antiplatelet antibody) using a solid-phase radioimmunoassay with 125I staphylococcal protein A. Two forms of antiplatelet antibody could be demonstrated: one that required drug to bind to platelets and one that bound to platelets in the absence of drug. Drug-dependent antiplatelet antibody required the simultaneous addition of drug and the Fc domain of the drug-dependent IgG molecule for binding to platelets. It did not require serum complement or factor VIII-related antigen for binding to platelets. Drug-dependent binding of antibody to platelets was saturation-dependent. Non-drug-dependent antiplatelet antibody of two patients (one with quinidine-induced thrombocytopenia and the other with acetaminophen-induced thrombocytopenia) reacted with autologous platelets as well as with homologous platelets, indicating that they were autoantibodies. Both autoantibodies had disappeared when their sera were tested 23 and 138 days, respectively, after withdrawal of their initial positive sera. Non-drug-dependent antiplatelet antibody binding could be demonstrated with the F(ab')2 fragment of the purified IgG of the serum of the second patient with quinidine DITP, who did not have detectable alloantibodies against HLA. None of the four patients with non-drug-dependent antiplatelet antibody had a past or present history of autoimmune thrombocytopenic purpura. PMID- 4040411 TI - [Pseudo-exfoliative glaucoma and laser trabeculoplasty]. PMID- 4040410 TI - Sustained thrombolysis with DNA-recombinant tissue type plasminogen activator in rabbits. AB - Tissue type plasminogen activator (t-PA) is an effective thrombolytic agent in experimental animals. The duration of the thrombolytic effect of infused t-PA is unknown. We compared the duration of the thrombolytic effect of t-PA with streptokinase by measuring the lysis of 125I-fibrin-labeled thrombi in rabbit jugular veins at different times after a bolus injection of the fibrinolytic agents. The pharmacodynamics of both thrombolytic agents were determined in rabbits using a sensitive ex vivo fibrinolytic assay. Streptokinase and t-PA were given as a bolus dose of 15,000 U/kg. There was no detectable circulating fibrinolytic activity 30 minutes after the bolus dose of t-PA and 120 minutes after the bolus dose of streptokinase. The t-PA injection produced 34% thrombolysis at 30 minutes, 90% thrombolysis at 120 minutes, and 96% thrombolysis at 240 minutes. The streptokinase injection produced 17% thrombolysis at 30 minutes, 34% at 120 minutes, and 34% at 240 minutes. These observations indicate that the thrombolytic effect of t-PA is sustained beyond its time of clearance from the circulation whereas the thrombolytic effect of streptokinase closely parallels its activity in the circulation. PMID- 4040412 TI - Scrotal pain. PMID- 4040413 TI - Giant haemangioma of the thigh (Kasabach-Merritt syndrome): resection with temporary clamping of the common iliac artery. AB - A giant haemangioma of the thigh in a 9-month-old infant girl with the Kasabach Merritt syndrome was operated upon with temporary clamping of the common iliac artery after previous attempts at treatment with external compression, prednisone and radiotherapy had failed. Secondary lymphoedema of the leg and foot appeared later and was successfully treated by Thompson's technique. PMID- 4040414 TI - Ankylosing spondylitis and Klinefelter's syndrome: does the X chromosome modify disease expression? PMID- 4040415 TI - Recurrent chorea gravidarum in four pregnancies. AB - An Arab woman developed recurrent chorea gravidarum in all four pregnancies that went to term, and none in the three pregnancies that ended in spontaneous abortion. She also developed an acute psychosis in one of these four pregnancies. A discussion of similar cases in the literature is undertaken. PMID- 4040416 TI - Use of early postpartum care in the home. PMID- 4040417 TI - Confidentiality and dangerousness in the doctor-patient relationship. The position of the Canadian Psychiatric Association. PMID- 4040418 TI - The safe use of cisplatin in hyperthermic isolated limb perfusion systems. AB - A patient presenting with aggressive squamous cell carcinoma successfully received cisplatin chemotherapy via hyperthermic, isolated limb perfusion (renal impairment ruled out systemic use). Human tumor stem cell assay identified cisplatin as the drug of choice and supports the potential benefit of this procedure in single therapeutic situations. The case illustrates the safety of cisplatin and the ability to give large doses of the nephrotoxic drug with no damage to renal function. The potential efficacy over systemic cisplatin has yet to be established except when systemic use is limited from renal dysfunction. PMID- 4040419 TI - Uterine papillary serous carcinoma. Complete response to combination chemotherapy. AB - A case of metastatic uterine papillary serous carcinoma with a complete response to chemotherapy is reported. The patient presented with vaginal, pelvic, and lymph node metastases 11 months after primary surgical resection was performed. A complete response to cyclophosphamide, Adriamycin (doxorubicin), and cisplatin was achieved. In this histologic pattern of endometrial adenocarcinoma, which behaves clinically like epithelial ovarian cancer, combination chemotherapy can offer significant response and palliation. PMID- 4040420 TI - Multiple myeloma associated with immune thrombocytopenic purpura. AB - Thrombocytopenia in patients with multiple myeloma is usually due to chemotherapy or marrow replacement with myeloma cells. Two patients with multiple myeloma who fulfilled criteria for the diagnosis of immune thrombocytopenic purpura are presented. The etiologic and therapeutic implications of this unusual association are discussed. PMID- 4040421 TI - Comparison of methotrexate and cisplatin for patients with advanced squamous cell carcinoma of the head and neck region: a Southwest Oncology Group Study. AB - One hundred eligible patients with inoperable, locally advanced or metastatic squamous cell carcinoma of the head and neck region following prior therapy were randomized to receive im methotrexate (50 patients) or iv cisplatin (50 patients). Methotrexate produced a complete plus partial response rate of 16.0% and cisplatin produced a partial response rate of 8.0%, with median durations of response of 18 and 8 weeks, respectively. The corresponding median survival times were 20 and 18 weeks. Methotrexate responders survived 60 weeks, versus 17 weeks for nonresponders. The corresponding survival times for cisplatin-treated patients were 38 and 18 weeks. Good pretreatment performance status had a significantly positive effect on survival (P = 0.04), but prior therapy did not. Toxicity secondary to either agent occurred with the expected frequency. The two agents examined showed comparable antitumor activity in patients with squamous cell carcinoma of the head and neck who had not previously received chemotherapy. PMID- 4040423 TI - Cisplatin-containing chemotherapy in the treatment of invasive thymoma: report of five cases. AB - Invasive thymomas are rare neoplasms arising from the epithelial cells of the thymus. In this paper, we report five cases of invasive thymoma treated with cisplatin either alone or combined with etoposide. Two partial responses (lasting 1 and 27+ months from the start of chemotherapy), two minor responses (lasting 1.5 and 13+ months from the start of chemotherapy), and one mixed response were observed. Further studies with cisplatin-containing regimens are warranted in the treatment of this rare tumor. PMID- 4040422 TI - Evidence for a novel hybrid immunotoxin recognizing ricin A-chain by one antigen combining site and a prostate-restricted antigen by the remaining antigen combining site: potential for immunotherapy. AB - We have used cell fusion technology to produce second-generation hybridomas which secrete a population of murine monoclonal antibodies (MABs), a portion of which are bifunctional antibodies. The bifunctional hybrid MABs produced are capable of recognizing ricin A-chain (RAC) via one antigen-combining site and a prostate restricted antigen via the other antigen-combining site of the IgG molecule. The second-generation hybridoma described in this report resulted from the fusion of spleen cells from mice immunized with purified RAC to hybridoma cells which secrete prostate-directed alpha Pro 15 monoclonal antibody. We have demonstrated that the MAB population secreted by the second-generation hybridoma can be physicochemically separated into distinct populations exhibiting differential binding to the cultured prostatic carcinoma cell surface and to RAC immobilized in a solid phase; specifically, a subset of the monoclonal antibody population which exhibits high binding to both prostatic carcinoma cells and to solid-phase RAC can be enriched by physicochemical methods. Binding of hybrid immunotoxin (HIT) MAB population to RAC can be quantitatively reduced by prior adsorption of the antibody population with prostate carcinoma cells; conversely, hybrid MAB binding to prostate carcinoma cells can be quantitatively reduced by prior adsorption with RAC. The biologic impact of the HIT has been evaluated by the ability of the HIT-RAC conjugate to reduce the uptake of 14C-amino acids into cellular protein. This effect is selective, since HIT-RAC conjugates do not exert an effect on labeled amino acid uptake by a cell line that does not express the target antigen recognized by the prostate-directed component of the hybrid MAB. Furthermore, depression of labeled amino acid uptake by prostate carcinoma cells exhibits a stoichiometric relationship with respect to both the concentration of HIT-MAB and to RAC to which the cells are exposed. The biologic impact of HIT-RAC conjugates on prostate carcinoma cells is enhanced markedly in the presence of lysosomotropic amines. PMID- 4040424 TI - Phase II trial of high-dose cisplatin in patients with malignant mesothelioma. AB - Twenty-five patients with advanced malignant mesothelioma were treated in a phase II trial with high-dose cisplatin (DDP). All patients had measurable or evaluable disease. Seven patients had received prior chemotherapy. DDP (120 mg/m2) with mannitol and prehydration was given every 4 weeks for two doses and then every 6 weeks. Of 24 patients evaluable for response, three had partial responses (3, 3+, and 9 months; response rate, 13%; 95% confidence limits, 4%-31%) and one had minor response. All responses occurred in previously untreated patients. High dose DDP has modest activity in malignant mesothelioma. PMID- 4040425 TI - Successful continuation of cisplatin therapy after partial recovery from acute renal failure. PMID- 4040426 TI - Effectiveness of cisplatin in the treatment of anal squamous cell carcinoma. AB - The therapeutic activity of cisplatin was explored in three consecutive patients with locoregional squamous cell carcinoma of the anus who received no prior therapy. One complete response and two partial responses were achieved. These data, although preliminary, strongly suggest that this disease is sensitive to cisplatin, and further trials are indicated to assess the precise role of this drug in the overall management of anal carcinoma. PMID- 4040427 TI - Phase I study of high-dose cytarabine and cisplatin in patients with advanced malignancy. AB - Nineteen patients with advanced malignancy participated in a phase I trial of high-dose cytarabine (ara-C) and cisplatin in combination. Dose and schedule were based on laboratory data indicating synergy for concurrent use of these drugs. Cisplatin (100 mg/m2) was administered during the 2nd and 3rd hours of a 3-hour ara-C infusion. The ara-C dose was escalated in subsequent patients following a starting dose of 1 g/m2. Two brief responses were noted. The study was terminated prematurely due to protracted (several weeks) nausea, occasional vomiting, and severe lassitude. PMID- 4040428 TI - Evaluation of a combination antiemetic regimen including iv high-dose metoclopramide, dexamethasone, and diphenhydramine in cisplatin-based chemotherapy regimens. PMID- 4040429 TI - Evaluation of cisplatin in children with recurrent brain tumors. PMID- 4040430 TI - [Vitamin A and zinc in the blood in chronic kidney failure]. PMID- 4040431 TI - [Ovarian hormones and the sex life of women]. PMID- 4040432 TI - [The sex life of men in infertile marriages]. PMID- 4040433 TI - [Problems with the Czechoslovak cytostatic agent Benin Spofa]. PMID- 4040434 TI - Use of aequorin for the appraisal of the hypothesis of the release of calcium from the sarcoplasmic reticulum induced by a change of pH in skinned cardiac cells. AB - A change of pH did not modify the sensitivity of aequorin to Ca2+, but an increase of pH enhanced the Ca2+ sensitivity of the myofilaments of a skinned canine cardiac Purkinje cell. The tension-pCa curve did not present any hysteresis when a given [free Ca2+] was reached from a higher versus from a lower [free Ca2+] in the presence of pH 6.60, 7.10 or 7.40. A rapid variation of pH in either direction failed to induce Ca2+ release from the sarcoplasmic reticulum (SR). The proton ionophores CCCP and gramicidin also failed to induce Ca2+ release from the SR. Increase of pH from 7.10 to 7.40 enhanced Ca2+ accumulation into the SR and, thereby, augmented the Ca2+ content of the SR. Consequently, the amplitude of a subsequent Ca2+ release triggered by a rapid increase of [free Ca2+] at the outer surface of the SR was increased. Conversely, a decrease of pH from 7.10 to 6.60 diminished the Ca2+ accumulation into the SR, the Ca2+ content of the SR and the amplitude of a subsequent Ca2+-induced release of Ca2+ from the SR. In addition, the optimum [free Ca2+] for triggering Ca2+-induced release of Ca2+ was shifted to higher [free Ca2+] values by a decrease of pH from 7.40 to 7.10 or 7.10 to 6.60. This may help to explain the enhancement of the aequorin light transient during acidosis in the intact cardiac muscle inasmuch as acidosis may increase the [free Ca2+] trigger at the outer surface of the SR by inhibiting Na+-Ca2+ exchange across the sarcolemma. PMID- 4040435 TI - Ultrastructural evidence for contacts between migrating L5222 rat leukemia cells and extracellular matrix components of the rat mesentery. AB - The nature of interactions between cells migrating through tissues and their structural surroundings are largely unknown. We have therefore examined the ultrastructural relationship between L5222 rat leukemia cells, moving through the loose connective tissue of the mesentery, and components of the extracellular matrix (ECM). Ultrathin tissue sections, fixed in the presence of ruthenium hexammine trichloride (RHT), revealed the following: Constitutents of fibrillar and nonfibrillar elements of the ECM are in contact with the plasma membrane of L5222 cells. Linear nonfibrillar ECM elements contact the plasma membrane at point-like sites, often associated with root-like structures present within the submembraneous microfilament mesh. Aggregates of ECM material are connected to patch-like cell membrane sites, associated with a condensed, plate-like part of the microfilament mesh. Point-like and patch-like contacts are more numerous at the anterior part of polarized migrating L5222 cells than on the posterior end. In round resting leukemia cells they are evenly distributed around the cell periphery. We suggest that the ECM-cell membrane contacts represent tissue adhesion sites. We therefore hypothesize that in migrating cells a coordinate interaction occurs between the contact sites and the continuous microfilament meshwork which results in a simultaneous backward movement of ECM-membrane contacts on the cell body and in a net forward movement of the whole cell. Since Dembo et al. (1981) present a similar mechanism for in vitro locomotion of granulocytes, we assume that blood cell locomotion in vivo and in vitro depends on similar molecular mechanisms: force generation by the cell, transmembraneous linkage between cytoskeletal and ECM elements, and membrane fluidity. The major difference in blood cell locomotion through a three-dimensional tissue or on a plane substratum would then be given by the distribution of contact sites, occurring around the cell periphery or limited to the ventral cell surface, respectively. PMID- 4040436 TI - [Antimicrobial effect of arbutin and an extract of the leaves of Arctostaphylos uva-ursi in vitro]. PMID- 4040437 TI - [Use of urodynamic examination methods in gynecology]. PMID- 4040438 TI - [Sperm motility, its regulation and methods of its recording]. PMID- 4040439 TI - [Sterility due to autoimmunity and its therapy]. PMID- 4040440 TI - [Long-term study of neonates at risk and neonates in a control group. II. Results of examinations of the children at 3 years of age]. PMID- 4040441 TI - [10 years' experience with the treatment of distal urethral stenoses in girls using urethrotomy]. PMID- 4040442 TI - Clinical pharmacology of high-dose cisplatin by Corden et al. PMID- 4040443 TI - Persistence of cyclophosphamide-induced damage in bone marrow as indicated by sister chromatid exchange analysis. AB - Various treatment protocols were used to investigate the time-dependent decrease in sister chromatid exchanges (SCEs) in bone marrow cells following treatment of C57Bl/6J X DBA/2J F1 (DB2F1) mice by i.p. injection of cyclophosphamide (15 mg/kg). The major factor in the time-related decrease in SCE-inducing lesions is the considerable cytotoxicity or selection of less highly damaged cells over successive cyclophosphamide post-treatment cycles. A constant rate of selection of 0.61 and 0.65%, respectively, was apparent over post-treatment cycles 1-2 and 2-3. In addition, second- and third-division SCE data produced by various protocols indicate persistence of a fraction of cyclophosphamide's SCE-inducing lesions for at least three post-treatment cycles. Comparison of the persistence of cyclophosphamide's SCE-inducing lesions with our previously reported data for diepoxybutane and ethyl carbamate reveals that the rate of repair of SCE-inducing lesions is inversely related to tumorigenic activities. PMID- 4040445 TI - Symposium on natriuretic hormone and hypertension. Beverly Hills, California, June 9, 1984. PMID- 4040444 TI - Protection against dimethylhydrazine-induced adenomatous tumors of the mouse colon by the dietary addition of an extract of soybeans containing the Bowman Birk protease inhibitor. AB - Dimethylhydrazine (DMH) induces adenocarcinomas of the colon and rectum in rodents; this animal cancer model system is thought to closely resemble human colorectal cancer. An extract of soybeans containing the Bowman-Birk protease inhibitor added to the diet of DMH-treated mice resulted in a significant suppression of adenomatous tumors of the colonic mucosa. Non-treated mice maintained on the same diet for most of their natural life-span (1.5 years) showed no observable health problems. PMID- 4040446 TI - Expression of MHC class II antigens on bile duct epithelium in experimental graft versus host disease. AB - Recently we observed the expression of MHC class II antigens on bile duct epithelium in human liver transplantation rejection. In this report we present evidence for the expression of MHC class II antigens on bile duct epithelium in experimental GVHD. These findings support the idea, that the target tissue elements in liver transplantation rejection and GVHD are the bile ducts, on the other hand this is a new experimental model for the analysis of MHC class II antigen expression on epithelial tissue. PMID- 4040447 TI - Changes in fibrinolytic activity during the course of a single hemodialysis session. AB - Cardiopulmonary bypass, a form of extracorporeal circulation, markedly increases blood fibrinolytic activity. Accordingly, we measured the effect of hemodialysis, another form of extracorporeal circulation, on fibrinolytic activity in 13 patients with end stage renal disease during and after a single hemodialysis session. Total fibrinolytic activity on fibrin plates, which reflects plasminogen activator levels, was below normal prior to dialysis, rose well above normal at one hour, and then dropped gradually so that just prior to the end of a dialysis session it was still significantly elevated. Within 30 minutes of the end of dialysis, fibrinolytic activity fell rapidly, approaching predialysis levels. In contrast, 5 patients studied before and 3 hours into a peritoneal dialysis session showed no change in their subnormal levels of plasminogen activator. Plasminogen and alpha-2 antiplasmin levels did not change significantly during the course of hemodialysis. Thus, hemodialysis, but not peritoneal dialysis, transiently increases fibrinolytic activity without consuming plasminogen, a pattern consistent with the release of tissue type plasminogen activator. PMID- 4040448 TI - A false-negative xenon-133 study in focal fatty infiltration of the liver. AB - A Xe-133 hepatic study was misleading when the absence of Xe-133 localization in an area of low CT numbers was considered to be negative for a diagnosis of focal fatty infiltration. PMID- 4040449 TI - Changes in succinic dehydrogenase activity in the central nervous system of mice during morphine dependence development, withdrawal and naloxone treatment. AB - The possible role of succinic dehydrogenase (SD) in producing physical dependence to morphine by affecting tissue respiration was investigated in Swiss albino mice during the development of morphine tolerance through a period of addiction and naloxone withdrawal therapy. Tolerance and physical dependence were induced by injecting the mice with morphine sulfate subcutaneously at 8-hour intervals, increasing the dose from 10 mg/kg BW every 24 h for 15 days. The animals were considered to be addicted when they were able to tolerate an otherwise lethal dose of 150 mg/kg 3 times a day. Results indicated that succinic dehydrogenase was inhibited throughout the 15-day period of morphine administration and that this effect was greatest in tolerant animals. Increasing the dose and duration of treatment did not cause further decreases in enzyme activity; instead, after 15 days levels of enzyme activity increased in addicted animals compared with tolerant mice. Furthermore, morphine abstinence for 2 days, markedly increased the levels of SD activity, while 6 days of abstinence had little effect. Naloxone withdrawal at each stage was associated with increased SD activity, but the increase was significant only in tolerant mice. PMID- 4040450 TI - A uni-directional urethral force gauge. AB - Until now urethral transducers have had poor circumferential resolution and have been inadequate for assessing whether the forces closing the female urethra are equally distributed around its circumference or whether they are greater in some directions than others. This paper describes a urethral force gauge which is capable of measuring urethral occlusive forces in a uni-directional manner because it is sensitive to forces around only 20 degrees of the urethral circumference. The gauge comprises a sensor, utilising two semi-conductor strain gauges, mounted at the tip of a 14 F silicone rubber catheter. It has been used in the investigation of 232 female patients and has proved to be reliable and robust. PMID- 4040451 TI - [The male climacteric. Endocrinologic profile and therapeutic prospectives]. PMID- 4040452 TI - [Effects of clofibrate on allyl alcohol poisoning in the rat]. PMID- 4040453 TI - Computed tomography detection of cervical spinal cord hemangioblastoma: a case report. AB - Hemangioblastomas of the spinal cord are uncommon, accounting for 1.6% and 2.1% of all spinal cord tumors (1). Until recently these vascular lesions were best evaluated angiographically. Several cervical hemangioblastomas have been studied by computed tomography with intravenous contrast medium enhancement (2-4). This report illustrates the use of computed tomography with combined intravenous and intrathecal contrast medium enhancement, which permitted preoperative diagnosis and treatment planning of an intramedullary hemangioblastoma. PMID- 4040454 TI - Glycolytic enzymes of human fetal and neonatal intraocular fluids. AB - The levels of the glycolytic enzymes, phosphohexose isomerase, aldolase and LDH and its isozymes, were ascertained in the aqueous of human stillbirths and premature neonate dead (19-24 weeks gestation) and compared with those of older neonates (28-41 weeks) of low survival due mainly to respiratory failure. The fetal aqueous displayed a much greater LDH-P level (mean mU/ml +/- SEM: 45,600 +/ 2550; 72 eyes) in contrast to the near-term infant value (2420 +/- 615; 27 eyes) and 8-20 times higher aldolase and phosphohexose isomerase levels. LDH-P of the fetal vitreous was much lower (5820 +/- 860 mU/ml; 25 eyes) and for lens employed as a filtered homogenate in saline (1:20), amounted to 52.2 +/- 4.2 mU/mg lens (24 eyes). The distribution of LDH isozymes in the fetal vitreous and lens homogenate and the near-term neonate aqueous as determined by polyacrylamide disc electrophoresis, was similar to that of the fetal aqueous, LDH-1 and LDH-5 being least and LDH-3 and LDH-4, the highest. A few small but significant differences were apparent as compared to the fetal aqueous isozymes and included decrements in vitreous LDH-4, lens LDH-3 and neonatal aqueous LDH-3 and increases in vitreous LDH-2 and near-term aqueous LDH-4. The current findings may have application to retinoblastoma for which higher aqueous LDH levels have been reported and employed as a diagnostic adjunct. However, the fetal aqueous LDH values far exceed those encountered in this embryonal-type tumour. PMID- 4040456 TI - In vitro activity of aztreonam--a new monocyclic beta-lactam antibiotic. AB - The in vitro antibacterial activity of aztreonam (SQ 26776), a new beta-lactam antibiotic, was measured by the agar dilution technique. Aztreonam is known to have a narrow spectrum with activity only against Gram negative bacteria. The strains tested were 223 clinical isolates from blood cultures obtained at Rigshospitalet, Copenhagen, Denmark. Its activity against E. coli, Klebsiella spp., Proteus spp., Enterobacter spp., Citrobacter, Salmonella typhimurium and Serratia marcescens was satisfactory with MIC values normally below 0.5 mg/l. However, six out of 135 strains of E. coli showed surprisingly high MIC values of eight and 16 mg/l. The activity against Pseudomonas spp. and Acinetobacter spp. were limited, but the majority were inhibited by concentrations of aztreonam between 2.0 and 8.0 mg/l. The MIC values for the tested anaeobic bacteria were high, ranging from 8.0 to above 512 mg/l. With its narrow spectrum of activity, aztreonam seems to be a valuable addition to the antibiotic arsenal. Clinical studies will determine its real value. PMID- 4040455 TI - Immunoreactive parathyroid hormone is present in subretinal fluids of the human eye. AB - (44-68) human Parathyroid hormone (hPTH) was studied in subretinal fluids (SRF) of 20 human eyes with rhegmatogenous retinal detachments. A (44-68) hPTH carboxyl mid-regional radioimmunoassay was used. Depending on the extent and the duration of the retinal detachments, (44-68) hPTH ranged between normal serum levels (ca. 100-300 pg/ml) up to excessive amounts of 4000 pg/ml with longstanding disease and proliferative vitreoretinopathy. Aqueous humors (AH) of one patient with bilateral iridocyclitis and complicated cataract ranged at 90-132 pg/ml (44-68) hPTH, whereas a control population undergoing surgery for senile cataracts had no detectable (44-68) hPTH in AH. The AH of one diseased eye of heterochromia complicata Fuchs showed excessive amounts of more than 4000 pg/ml (44-68) hPTH. PMID- 4040457 TI - [Bromocriptine in the treatment of galactorrhea with anovulation; report of 53 cases]. PMID- 4040458 TI - [Ultrastructure observation of the inoculated human esophageal carcinoma cell line (Eca 109) in nude mice]. PMID- 4040460 TI - The juvenile-peripubertal transition period in the female rat: establishment of a diurnal pattern of pulsatile luteinizing hormone secretion. AB - Previous descriptions of pulsatile LH release in immature female rats have been mostly inaccurate because of infrequent blood sampling, discontinuous and unbalanced blood replacement procedures, and possibly because of the use of a heterologous RIA. The present study was undertaken to circumvent these problems and to characterize more precisely the changes in episodic LH secretion previously observed during the juvenile-peripubertal transitional period (27-38 days of age). Changes in LH levels were measured in plasma samples obtained every 5 min from unrestrained conscious animals using a recently developed technique that permitted continuous withdrawal of blood for 4-5 h and simultaneous replacement with an artificial blood mixture. In virtually all of the rats, LH release was pulsatile. In both the juvenile (27-29 days old) and peripubertal (30 38 days old) animals, mean plasma LH levels and LH pulse amplitude were low in the mornings. A similar pattern of LH secretion was found in the afternoon during the juvenile period. In contrast, most of the peripubertal animals exhibited an afternoon increase in LH pulse amplitude. A change in pulse frequency was not detected at this time, but a 1.8-fold increase in mean LH levels suggests that large amplitude pulses may be accompanied by low amplitude, high frequency pulses not revealed by the 5-min sampling paradigm. Some of the peripubertal rats (5 of 12) had plasma LH profiles in which the large amplitude pulses were accompanied by a midafternoon minisurge of secretion which lasted for up to 2 h and reached peak levels of 174 +/- 19 ng/ml; the LH surge at first proestrus was greater than 1000 ng/ml. The results demonstrate the prepubertal development of an afternoon increase in LH pulse amplitude and the appearance of a more prolonged and larger secretory episode of LH secretion (minisurge). Disclosure of a concomitant increase in pulse frequency may necessitate blood sampling at more frequent intervals. It is suggested that the changes in the mode of LH release described here may enhance peripubertal ovarian steroidogenesis and provide an appropriate stimulus for initiating the final stages of ovarian development. PMID- 4040459 TI - Endogenous opioid peptides participate in the modulation of prolactin release in response to cervicovaginal stimulation in the female rat. AB - Naloxone, a specific opiate receptor antagonist, was used to evaluate the influence of endogenous opiate peptides on PRL secretion during various stages of the estrous cycle and after cervicovaginal stimulation. Naloxone (0.2 mg/kg, iv) administered at 0930 h suppressed basal 1000 h PRL levels on each day of the estrous cycle, but had no effect on the PRL surges occurring on the afternoon of proestrus and estrus. These afternoon surges could only be suppressed when naloxone was given immediately before the onset of the surge at 1330 h, suggesting a critical period for naloxone action. Later injections (at 1530 and 1730 h) had no further suppressive effects, although these injections suppressed the basal PRL secretion occurring during diestrous days I and II to near undetectable levels. In contrast, the immediate (1000 h) and afternoon PRL discharges triggered by cervicovaginal stimulation at 0930 h on proestrus, estrus, and diestrous day I were significantly suppressed by a single injection of naloxone, but only when it was administered before application of the stimulus. Moreover, this single naloxone injection significantly inhibited the long term PRL surges occurring during days 2 and 4 of pseudopregnancy in animals stimulated on estrus and diestrous day I. Naloxone treatment significantly shortened the duration of pseudopregnancy but did not prevent it, indicating that only minimal levels of PRL may be necessary to initiate and maintain pseudopregnancy. This striking difference in the time at which naloxone suppressed the stimulus-induced PRL discharges (compared to the spontaneous surges) suggests that endogenous opiate peptides also process the sensory information necessary for establishment of PRL surges during pseudopregnancy. The marked dependence of the spontaneous as well as the stimulus-induced PRL discharges on the stage of the estrous cycle support established evidence that ovarian steroids enhance endogenous opiate activity or facilitate the transfer of information along opiatergic pathways for the generation of PRL surges. PMID- 4040461 TI - Differential changes in the mechanisms controlling luteinizing hormone and prolactin secretion in middle-aged female rats. AB - Serum luteinizing hormone (LH) and prolactin (PRL) concentrations were measured in young (3-4 month old) and middle-aged (10-12 month old) intact female rats on proestrus, in ovariectomized rats after two estrogen injections (estradiol benzoate; EB, 10 micrograms/100 g body weight, s.c.) or after preoptic stimulation in EB-primed ovariectomized rats. Only animals showing regular 4-day estrous cycles were selected for the experiment. The magnitude of proestrous LH surge was significantly smaller in middle-aged than in young rats. Two BE injections, at noon on Days 0 and 3, in ovariectomized middle-aged rats failed to induce surges in LH secretion on Day 4 whereas the same treatment produced LH surges in ovariectomized young rats. The preoptic electrochemical stimulation (50 microA for 60 sec) produced a prompt rise in serum LH levels in ovariectomized EB primed young but not in middle aged rats. The preoptic stimulation with a larger current (200 microA) induced LH secretin in middle-aged rats. In none of these situations serum PRL concentrations were different between young and middle-age rats. These results suggest differential aging rates in the preoptic mechanisms governing LH and PRL secretion in the rat. The function of the preoptic ovulatory center in responding to the estrogen positive feedback action and inducing LH secretion may become impaired and independent of the PRL control mechanism, even before the regular estrous cycle terminates. PMID- 4040463 TI - A model for intracellular complexation between gene-5 protein and bacteriophage fd DNA. AB - A structural model for the helical intracellular complex formed between the gene 5 DNA-binding protein (G 5 BP; approximately 1274 copies) and bacteriophage fd DNA has been derived by an atomic-contact analysis approach. These studies depended in large part on the recently determined high-resolution structure of the G 5 BP dimer and cross-correlations with physical-chemical data available from other techniques. The approach was to systematically scan the full set of helical complexation parameters involved, based upon observed structural and orientational constraints, to determine those compatible with both the structure of the G 5 BP dimer and the overall dimensions of the full complex. This process was monitored throughout by close scrutiny of dimer-dimer contacts and the use of hard-copy and interactive graphics devices. Instead of the wide variety of possibilities that had been expected from such an approach, only one satisfactory assembly of DNA and G 5 BP dimers could be found. The results indicate that phage DNA will be wound to the outside of the helical protein ribbon that forms the core of intracellular complex at a density of five nucleotides per G 5 BP monomer. Bound DNA strands are positioned in two contiguous binding channels, which form as a consequence of the interactions of complexed G 5 BP dimers. These channels run just inside the outer extended beta loops, composed of residue 20 30, and are separated by approximately 3.2 nm. The DNA phosphate backbone is bound at a substantially smaller radial distance (approximately 3.5 nm) than the maximum radius of the intracellular complex as a whole (approximately 4.5 nm) since bound DNA is embedded within these well-defined binding channels. Our studies also indicate that a number of sterically unacceptable contacts, involving residues 38-42, prevent complexation of otherwise complementary dimer surfaces in the absence of nucleic acids. In the process of binding DNA, these residues change conformation thereby allowing self-assembly of dimer units into a helical structure. We propose that these residues act as a two-position stereochemical switch that allows or disallows complex formation in response to the absence or presence of DNA. PMID- 4040462 TI - Location of transcriptional control signals and transfer RNA sequences in Torulopsis glabrata mitochondrial DNA. AB - Determination of sequences from the nine regions separating the large genes in the 19-kbp mitochondrial DNA from Torulopsis glabrata has led to the identification of 23 tRNA genes and to the recognition of two types of short repeated sequence implicated in mitochondrial genome expression. The two short repeated sequences are a nonanucleotide motif, 5'-TATAAGTAA-3' and a dodecanucleotide motif, 5'-TATAATATTCTT-3'. By RNA sequence determination it has been found that primary transcripts of the small and large rRNAs commence at the 3' penultimate adenine of the nonanucleotide sequence. This motif has also been found in the DNA sequence upstream from f-methionine, phenylalanine, leucine, tyrosine and glycine tRNAs, cytochrome oxidase subunit 2 and ATPase subunit 9. The dodecanucleotide sequence is found at least once in each of the nine regions between the large genes. Determination of the 3' ends of the small and large rRNAs has shown their location to be 8 and 23 nucleotides downstream from the dodecanucleotide sequence. This motif is thought to be involved in signalling processing of polycistronic transcripts. Such transcripts are invoked to account for the production of mRNAs for cytochrome b, cytochrome oxidase subunits 1 and 3, and the joint mRNA for ATPase subunits 8 and 6 genes that lack an adjacent upstream nonanucleotide transcription initiation signal sequence. Processing of polycistronic transcripts at tRNA sequences is also implicated in the formation of mature mRNAs. From the position of tRNA genes relative to the nonanucleotide motif it appears that clusters of these genes are co-transcribed with downstream sequences for cytochrome oxidase subunits 1 and 3. PMID- 4040464 TI - Arm muscle and fat in the evaluation of nutritional status. A study of African pre-school children in three different environments. AB - Anthropometric variables were collected in 10230 clinically healthy children under 5 years of age. The children belong to three African tribes living in different environments. The conventional anthropometric methods of screening children nutritionally at risk were used and their validity is scrutinised. It is shown that, to assess nutritional condition, arm muscle area and arm fat area add essential information to data on weight-for-age, weight-for-height and arm circumference-for-age. It is suggested that the choice of anthropometric methods and standards must be adapted to the ecological situation. PMID- 4040466 TI - Adriamycin and cis-platinum in advanced ovarian cancer. AB - Forty-eight patients with stage III and IV ovarian epithelial carcinoma were treated with single doses of adriamycin (ADM) 50 mg/m2 and cis-platinum (DDP) 50 mg/m2 every month for nine courses. The pathologically proven response rate was 52.2%, with 22.7% complete response and 29.5% partial response. Median survival was 22 months for all patients, 25 months in stage III and 15 months in stage IV. This study confirms that ADM-DDP is a valuable drug regimen in advanced ovarian carcinoma but further progress is needed to improve the cure rate, which remains low. PMID- 4040465 TI - Daily intake of selenium by bottle-fed infants in Belgium. AB - The selenium content of commercial infant formulae, processed milk and beikost was measured by hydride generation atomic absorption spectrometry after previous wet acid digestion. The median daily intake by infants (1-6 months) fed milk, soya or cereal-based infant formulae was 3.0-7.8 micrograms/day; lower than the mean daily intake by Belgian breast-fed infants (6.1-8.6 micrograms/day) and cow's milk bottle-fed infants (7.6-10.8 micrograms/day). PMID- 4040467 TI - Striatal dopamine receptor sensitivity after subchronic fencamfamine in the rat. AB - Dopamine (DA) receptor sensitivity was assessed in the rat striatal system following subchronic treatment with fencamfamine or saline for 7 days (10 mg/kg i.p.). Seventy-two hours after the last injection the stereotyped behaviour and general activity induced by apomorphine or saline were evaluated. Apomorphine (2.0 mg/kg s.c.) induced a decrease of the stereotypic response when fencamfamine pretreated animals were compared to saline-treated ones while apomorphine (0.02 mg/kg s.c.) failed to alter the general activity of animals, treated with fencamfamine or not. In biochemical experiments subchronic fencamfamine did not alter the effects of apomorphine (0.02 mg/kg s.c.) in reducing homovanillic acid (HVA) and dihydroxyphenylacetic acid (DOPAC) striatal levels, when compared to saline. In addition we observed a slight but significant reduction in the total dopamine receptor content in the striatum labelled by [3H]spiroperidol. These findings indicate that subchronic fencamfamine treatment leads to a desensitization of postsynaptic DA receptors in rat striatum. PMID- 4040468 TI - A monoamine oxidase inhibitor reverses the 'separation syndrome' in a new hamster separation model of depression. AB - A broad spectrum monoamine oxidase inhibitor, tranylcypromine sulfate (Parnate) was tested in a new hamster separation model of depression. In this paradigm, male dwarf hamsters show increases in body weight, decreases in exploratory behaviors, and decreases in social interactions, when separated from female mates. Tranylcypromine (10 mg/kg s.c. daily for 14 days) effectively reduced body weight, increased exploration, and increased social interaction, in the separated males. Subsequent treatment with saline restored the separation-induced changes in body weight, exploratory behaviors, and other social behaviors. The 'separation syndrome' in dwarf hamsters appears to be completely reversed by at least one antidepressant treatment. PMID- 4040469 TI - Differential effects of morphine on core temperature in stressed and non-stressed rats. AB - The effects of morphine on body temperature were studied in rats in two different states - stressed and non-stressed. Morphine injected subcutaneously (s.c.) produced a dual action on body temperature in non-stressed rats. Hyperthermia occurred at lower doses (2.5-10 mg/kg) while hypothermia was produced with a higher dose (20 mg/kg). Both of these effects of morphine were reversed by naloxone (0.1-5.0 mg/kg). Stressing the rats (immobilization with wire mesh) produced slight hypothermia which was markedly potentiated by morphine (5-20 mg/kg) in a dose-dependent manner. Enhancement of hypothermia by morphine in the stressed animals was antagonized by pretreatment with naloxone (0.1-5.0 mg/kg). When rats were treated with morphine (10 mg/kg) 1 h before stress, and were then exposed to immobilization stress, the hyperthermia exhibited in the non-stressed state changed to hypothermia in the stressed state. When the rats which were treated with morphine and then stressed for 1 h were released from stress, the hypothermia observed in the stressed state progressively changed to hyperthermia. Furthermore, these morphine effects, i.e. hyper- and hypothermia in the non stressed and stressed states, respectively, were reversed but not eliminated by naloxone. These results suggest that the effects of morphine on core temperature in rats are altered depending upon the state of the animals. That is, morphine appears to have a dual action, hyperthermia in the non-stressed state and hypothermia in the stressed state. It also appears that these actions are mediated via opiate receptors. PMID- 4040470 TI - Comparison of the effects of forskolin and isoprenaline on tracheal, cardiac and skeletal muscles from guinea-pig. AB - Forskolin, a potent activator of adenylate cyclase, and isoprenaline, an unselective beta-adrenoceptor agonist, were studied in vitro on tissues from guinea-pig with respect to relaxation of the carbachol-contracted trachea, increase in the force of contraction of the papillary muscle and depression of subtetanic contractions of the soleus muscle, three well-characterized beta adrenoceptor-mediated effects. Forskolin and isoprenaline relaxed the trachea and increased the force of contraction of the papillary muscle. Isoprenaline but not forskolin caused a depression of the subtetanic contraction of the soleus muscle. Forskolin did not seem to potentiate the effects of isoprenaline on the tissues studied; the combined effects appeared to be a mere addition. Forskolin did not increase the efficacy of the partial agonist prenalterol either. It is concluded that there is no simple relation between c-AMP generation and the functional response to beta-adrenoceptor agonists. Forskolin should not be used uncritically to probe beta-adrenoceptor-mediated effects. PMID- 4040471 TI - The influence of verapamil on the gastric effects of stress in rats. AB - The influence of verapamil on stress- or bethanechol-induced gastric effects was investigated in rats. Intraperitoneally injected verapamil (1, 2 or 4 mg/kg), given 30 min beforehand, dose-dependently prevented gastric glandular ulceration, mast cell degranulation and the increased stomach wall contractions evoked by restraint at 4 degrees C for 1 h. Gastric acid secretion, as well as ulceration in both the forestomach and glandular segment, produced by subcutaneously injected bethanechol (3.2 mg/kg) were also inhibited. It is concluded that decreased amine release from the mast cells, stomach wall relaxation and reduced gastric acid were responsible for the ulcer-antagonising effects of the calcium entry blocker. The possible antiulcer actions of verapamil are discussed in the light of present knowledge regarding calcium involvement in the various mechanisms thought to contribute to the pathophysiology of stress ulceration in rat stomachs. PMID- 4040472 TI - Cross-species neural transplants of embryonic septal nuclei to the hippocampal formation of adult rats. AB - In the absence of immunosuppressive treatment, suspensions of cells from the developing septal region of mouse embryos were transplanted successfully into the denervated hippocampal formations of adult rat hosts. The longitudinal recovery of acetylcholinesterase (AChE)-containing fibers in the host was the index of transplant success. In transplant recipients, the fornix-fimbrial interconnection between the septum and hippocampal formation was severed unilaterally, and two 5 microliter aliquots of cell suspension were injected into the hippocampal formations of host rats. Five sets of controls included one in which animals received no surgical intervention (Normal Controls), and another which was subjected to a sham operation (Sham Controls). The fornix-fimbria pathway was transected unilaterally in Lesion Control animals, while Hippocampal Controls received the same lesion plus two injections of non-cholinergic cells from the hippocampal formations of mouse embryos. Injection Controls were subjected to a fornix-fimbria transection and given two injections of debris and dead cells in saline. The cross-species transplants induced the return of a normal AChE laminar pattern in the recipient rats. The density of the laminar pattern, quantified with laser densitometry, was greatest in transplants that had survived for one week, but only in sections adjacent to the injection sites. Although the density decreased from the first through third weeks of survival, overall density of AChE staining stabilized from the fourth through 17th weeks of survival. Because the success rates of these cross-species transplants were similar to those reported for homogenic tissue, it was concluded that the rat brain is a suitable host for xenogenic transplants of septal neurons from embryonic mice. PMID- 4040473 TI - Schistosoma mansoni: lectin-dependent cytotoxicity of hemocytes from susceptible host snails, Biomphalaria glabrata. AB - Normally benign hemocytes from a strain (M-line) of the snail, Biomphalaria glabrata, susceptible to Schistosoma mansoni, became cytotoxic toward the sporocyst stage if the parasite was first treated with the lectin, concanavalin A. Concanavalin A binding was inhibitable with alpha-methyl mannoside and killing was dose-dependent. Maximal levels of concanavalin A-induced cytotoxicity were comparable with levels observed when hemocytes from a resistant snail strain (13 16-R1) encountered untreated sporocysts. Induction of the cytotoxic response did not occur if hemocytes alone were pretreated with the lectin. A unique method incorporating ultraviolet microscopy and the vital fluorescent dye, eosin Y, was used for discriminating between live and dead sporocysts. This model may prove useful in understanding mechanisms used by invertebrate effector cells in recognition and killing of invading organisms. PMID- 4040474 TI - Synthesis of new arylanalogs of ketamine. AB - New, seven-step synthesis of arylanalogs of ketamine, starting from easily available phenylcyclohexane derivatives, is reported. Pharmacological investigations on the compounds obtained are described. PMID- 4040475 TI - Inhibition of hCG-stimulated adenylate cyclase in purified mouse Leydig cells by the phorbol ester PMA. AB - The tumour-promoting phorbol ester, PMA (phorbol 12-myristate 13-acetate), markedly reduced the steroidogenic response of mouse Leydig cells to stimulation by hCG and cholera toxin. However, 8Br-cAMP-and forskolin-stimulated steroidogenesis was not inhibited by PMA. PMA did not inhibit hCG-induced steroidogenesis in the simultaneous presence of 1 microM forskolin. The analysis of intracellular cAM P indicated that the PMA-induced inhibition of steroidogenesis was the result of an impaired cAMP accumulation. Adenylate cyclase in membranes prepared from PMA-treated cells showed a diminished response to hCG, GTP, guanosine 5'-[beta, gamma-imido]triphosphate [Gpp(NH)p] or to a combination of the stimulants. PMA, however, was unable to inhibit adenylate cyclase when added directly to the membrane preparation from untreated cells. As previous observations have indicated that 125I-hCG binding and phosphodiesterase activity in mouse Leydig cells are not influenced by PMA, it is concluded from the present study that the site of inhibition has to be localised to the regulatory guanine nucleotide binding protein of the adenylate cyclase system. PMID- 4040476 TI - Isolation from bovine brain of tropomyosins that bind to actin filaments with different affinities. AB - Tropomyosin was isolated from bovine brain using mild conditions thereby avoiding heat precipitation. Separation by DEAE ion exchange chromatography yielded a 33 kDa tropomyosin and a mixture of 30 and 32 kDa tropomyosin. Binding of the tropomyosins to actin filaments was measured by a newly developed method. The binding was assayed by the retarding effect of tropomyosin on actin polymerization. The 33 kDa tropomyosin was found to bind to actin filaments with considerably higher affinity than the 30 and 32 kDa tropomyosin. PMID- 4040477 TI - Age-dependent changes in the level of a 34 kDa DNA-binding protein in developing chick embryo liver. AB - The relative amounts of a DNA-binding protein of 34 kDa increased during the early stages of development of chick embryo liver. The content of this protein reached a maximum in 18-19-day-old embryonic livers and decreased afterwards in older embryonic and post-natal chick livers. The 34 kDa polypeptide is the major DNA-binding protein (DBP) of embryonic liver and it preferentially binds to single-stranded DNA. The quantity of the 34 kDa DBP was relatively very low in embryonic muscle, heart and brain. PMID- 4040478 TI - 2',3'-Dialdehyde of GTP blocks regulatory functions of adenylate cyclase NS protein. AB - Preincubation of bovine caudate nucleus membranes with the 2',3'-dialdehyde of GTP (oGTP) reduces adenylate cyclase activation by guanylyl imidodiphosphate (GppNHp) in a time-dependent fashion. A slower rate of inhibition is observed if membranes are treated with both GTP and oGTP. The efficacy of oGTP action is enhanced by raising the Mg2+ concentration. Reduction of adenylate cyclase sensitivity to GppNHp is followed by an irreversible decrease of enzyme stimulation by forskolin. Addition of a Lubrol soluble preparation from guinea pig lung membranes to oGTP-treated caudate nucleus membranes causes restoration of the adenylate cyclase sensitivity to GppNHp. These data suggest that oGTP blocks the GTP-binding site of the adenylate cyclase system localized on the Ns protein. Such modification leads to the elimination of the Ns-mediated regulation of the enzyme. PMID- 4040480 TI - Peritoneal fluid plasminogen activator activity in endometriosis and pelvic adhesive disease. AB - Plasminogen activator activity in PF was assayed by the fibrinolysis method described by Strickland and Beers. In 45 patients studied, there were no discernible differences according to whether patients had endometriosis and/or pelvic adhesive disease. No differences were detected according to when in the menstrual cycle the sample of PF was obtained. These data are in concordance with a previous report and taken together suggest that there is no difference in fibrinolytic mechanisms in PF in patients with or without endometriosis and/or pelvic adhesive disease, when compared with control subjects. If such differences exist, they may be present in the tissues, per se, but are not discernible in PF. PMID- 4040479 TI - Possible steroid binding site common to adrenal cytochrome P-450scc and prostatic steroid binding protein. AB - By searching the entire PIR-protein-sequence data base, we have found that a dodecapeptide sequence in bovine adrenal cytochrome P-450scc is closely related to that in rat prostatic steroid binding protein. The two proteins belong to unrelated protein families, but both have steroids as substrates or ligands. Thus, the dodecapeptides may be important for substrate/ligand recognition in the individual proteins. PMID- 4040481 TI - [Changes in cardiovascular functions and adrenergic innervation of the heart during immobilization stress in rats]. AB - In 40 rats immobilized for 30 hrs, a reduction of density of distribution of the adrenergic neural terminals in myocardium occurs along with changes of the cardio vascular functions. The death of animals in immobilization was due to a progressive drop of arterial pressure. Immediately before death the density reduction of adrenergic terminals was the most obvious. Disturbances of the cardio-vascular functions in immobilization stress seem to be related to the reduction of density of the adrenergic neural terminals distribution in the myocardium. PMID- 4040482 TI - [Bio- and immunoactive luteinizing hormone in negative feedback action of gonadal steroids]. AB - To clarify the possible intervention of gonadal steroids on the secretion of bioactive LH from the pituitary, the levels of plasma LH were measured by in vitro bioassay as well as radioimmunoassay, and their changes in specific endocrine conditions were investigated. The ratio of bioactivity to immunoactivity (B/I ratio) of LH in patients with hypergonadotropic hypogonadism and in postmenopausal women was significantly greater than that in women during the follicular phase of the menstrual cycle, and estradiol levels in the former groups were significantly lower than those of the latter group. In cases of gonadotropin-secreting pituitary tumor with high LH and normal estradiol levels, B/I ratio was found at a level similar to that during the follicular phase. The administration of combined pills decreased the high B/I ratio of oophorectomized women to levels comparable to those in the normal follicular phase. Although bioactive LH responded in all groups to LH-RH with a similar pattern to that observed with immunoactive LH with a peak value 15 approximately 30 min. after the stimulation, followed by a gradual decrease thereafter, the B/I ratio of women during the follicular phase was the lowest at 15 min. and returned up to the initial value within 60 min. after the injection of LH-RH. In contrast, this drop of the B/I ratio did not occur in 7 out of 15 cases composed either of hypergonadotropic hypogonadism or postmenopausal women. The peak values of LH in patients without decrease in B/I ratios were higher than those of women showing decreased B/I ratios. In addition, circulating levels of gonadotropin alpha subunit did not affect the B/I ratio. These results suggest that circulating levels of gonadal steroids regulate the secretion and synthesis of LH quantitatively as well as qualitatively. PMID- 4040483 TI - Peripheral panretinal photocoagulation and perfluoropropane/air mixture in vitreoretinal surgery for proliferative vitreoretinopathy. PMID- 4040484 TI - Use of monoclonal antibodies for detection and therapy of carcinomas. PMID- 4040485 TI - High pH-induced acrosome reaction and Ca2+ uptake in sea urchin sperm suspended in Na+-free seawater. AB - The egg jelly-induced acrosome reaction of sea urchin sperm requires the presence of Ca2+ and Na+ in seawater at its normal pH 8. Sperm suspended in seawater at pH 9 undergo the acrosome reaction in the absence of jelly. We have attempted to understand the role of external Na+ in this reaction. Sperm were suspended in Na+ free seawater and the percentage of acrosome reaction and the amount of Ca2+ uptake were determined as a function of external pH. High pH (9.0) in Na+-free medium without jelly triggered a high percentage (above 65%) of sperm acrosome reactions and a two to fourfold increase in Ca2+ uptake. Both the percentage of acrosome reactions and the amount of Ca2+ uptake were similar to those induced by either jelly or pH 9 in Na+-containing seawater. On the other hand, the absence of Na+ in seawater inhibits jelly from inducing Ca2+ uptake and acrosome reactions at pH 8.0 and even at pH 8.5. These results indicate that the Na+ requirement for the acrosome reaction induced by jelly is lost when triggering is by high pH. In contrast, Ca2+ was strictly required since sperm did not react in Ca2+-free seawater at pH 9. We also found that like the jelly-induced acrosome reaction the high-pH-induced acrosome reaction and Ca2+ uptake in complete and Na+-free seawater were inhibited by D600. This finding suggests that the same transport system for Ca2+ uptake associated with the acrosome reaction operates at both triggering conditions, i.e., jelly or pH 9. Although D600 is not now considered a specific blocker, its effect has suggested the involvement of Ca2+ channels in the acrosome reaction. This proposal is supported by our results with nisoldipine, a highly specific inhibitor of calcium channels. The drug inhibited both the sperm acrosome reaction and Ca2+ uptake induced by jelly or pH 9 in complete seawater. PMID- 4040486 TI - Acute left ventricular filling time and rate changes in hypertrophic cardiomyopathy after verapamil and propranolol evaluated by nuclear stethoscope. AB - We have undertaken the present study to evaluate the acute effects of propranolol and verapamil on the diastolic function in patients with hypertrophic cardiomyopathy. We used a non imaging isotope device, the nuclear stethoscope, that has been so far mainly employed for assessment of systolic function, although fitted for detecting diastolic filling rates and times as well. Relative cardiac output, ejection fraction, rapid and slow filling times and rates were measured in five patients suffering from hypertrophic cardiomyopathy in basal conditions and 10.20 and 30 minutes after i.v. administration for either propranolol or verapamil, with a time interval of at least 24 hours between the two acute drug studies. With respect to the baseline values only verapamil showed a significant improvement in rapid and maximum filling rates, suggesting that diastolic function is more beneficially affected by Ca-entry blockers rather than beta-blockers in hypertrophic cardiomyopathy. PMID- 4040487 TI - [The FG syndrome (McK 30545). Description of 2 cases with subaortic stenosis]. AB - This paper reports on two brothers affected by FG syndrome (a rare X-linked syndrome with multiple congenital anomalies and mental retardation) and subvalvular aortic stenosis of the discrete type. This is a previously unrecognized association. The FG syndrome was firstly described by Opitz and Kaveggia in 1974. Nearly 20 cases have been reported: congenital heart diseases previously reported are atrial septal defect, ventricular septal defect and hypoplastic left heart. The clinical appearance of the two cases we have observed was that of mental retardation and typical features including abnormal facies (dolicocephaly, frontal prominence, poorly modeled auricles, micrognathia, prominent lower lip and lack of expression), anteriorly displaced anal opening, clinodactyly, great broad toes. A chromosome study showed a normal 46 XY constitution. Discrete subvalvular aortic stenosis was diagnosed by typical physical and echocardiographic findings. PMID- 4040488 TI - Detection and clinical significance of acetone-insoluble liver cell membrane antigen in sera of patients with chronic active liver diseases. AB - An enzyme-linked immunosorbent assay was developed to detect insoluble liver cell membrane antigen (LMAg) which gives rise to serum LMA (anti-LM) in HBsAg-negative patients. The optical density (OD) ratio of the average LMAg level of normal subjects was less than 1.2. In HBsAg-positive cases, high LMAg levels (OD ratio greater than 2.4) were noted in 8 of 8 patients with acute hepatitis (AH), 3 of 8 with chronic persistent hepatitis (CPH), 5 of 10 with moderate chronic aggressive hepatitis (CAH), 7 of 10 severe CAH and 4 of 8 with liver cirrhosis (LC). In HBsAg-negative cases, however, high LMAg levels were noted in only 6 of 8 patients with AH, 1 of 10 with CPH, 1 of 10 with moderate CAH, 1 of of 10 with severe CAH, 0 of 8 with LC, 0 of 8 with fatty liver and 5 of 10 with alcoholic hepatitis. In micro-immunodiffusion experiments, intensively absorbed rabbit anti rat LM precipitated two organ-specific components of rat liver homogenate, one of which was identical to liver specific protein (LSP). In immunohistochemical demonstrations of LMAg and LSP, anti-LM, prepared from the serum of a HBsAg negative CAH patient, bound to both human and rat acetone-fixed liver cell membranes, but not to those of human or rat kidneys. Absorbed rabbit anti-rat LM also bound to liver cell membranes, but absorbed anti-rat LSP lacked organ specificity when assayed with the immunofluorescence technique using acetone fixed liver sections. In conclusion, the appearance of serum LMAg was associated with high-SGPT patients and HBsAg-positive CAH patients. PMID- 4040489 TI - Stress-induced elevation of plasma alpha-MSH and endorphin in brown trout, Salmo trutta L. AB - Handling and confinement caused a pronounced elevation in the plasma cortisol levels of brown trout. This response was more rapid, and the elevation greater, at 13.4 than at 5 degrees although basal cortisol levels were also higher at the warmer water temperature. The large increase in plasma cortisol caused by handling and confinement was not accompanied by any changes in the plasma levels of either alpha-MSH or endorphin. However, when handling and confinement was combined with a thermal shock, not only was there a rapid and pronounced elevation in plasma cortisol, but there were also concomitant and sustained rises in the plasma levels of both alpha-MSH and endorphin. The levels of a alpha-MSH and endorphin induced by the thermal shock were considerably higher than those recorded in long-term, black-adapted brown trout, the only other circumstance in fish known to cause an elevation of the plasma levels of these two peptides. These results indicate that handling and confinement only activated the corticotrophs of the pars distalis, not the melanotrophs of the neurointermediate lobe, whereas when combined with a thermal shock, both cell types were activated. PMID- 4040490 TI - Primary chemotherapy and postoperative adjuvant chemotherapy in the treatment of squamous cell carcinoma of the uterine cervix. AB - Two cases with squamous cell carcinoma of the cervix stage IIB with primary tumor mass about 2 X 2 X 2 cm were treated with primary chemotherapy of cis-platinum, 20 micrograms/m2 body surface intravenously daily for 5 consecutive days. Papanicolaou smear turned negative after two courses of chemotherapy in both cases. One of those was followed by radical hysterectomy with lymphadenectomy which confirmed that there was no evidence of disease by histopathology. The third case with stage IIIB and bulky tumor with involvement of pelvic and left common iliac lymph nodes was treated with simple hysterectomy followed by adjuvant chemotherapy with the same medication described above. Complete responses were obtained in all three cases and they are now doing well in a tumor free state for 26, 30, and 28 months, respectively. PMID- 4040491 TI - Studies on the effects of estrogen on the antibody response in asymptomatic HB virus carrier. AB - Antibody-forming cells against trinitrophenylated sheep red blood cells (TNP SRBC) were induced to a similar extent when peripheral blood mononuclear cells from normal individuals, patients with chronic active hepatitis, and asymptomatic HBV carriers were stimulated in vitro with pokeweed mitogen (PWM). Although these antibody responses were significantly augmented by adding estrogen simultaneously with PWM to mononuclear cell cultures prepared from normal individuals and patients with chronic active hepatitis, no such augmentation was demonstrable in asymptomatic carriers. The DNA synthesis in PWM-stimulated mononuclear cells was also increased by estrogen in normal individuals and patients with chronic active hepatitis, but this was not the case in asymptomatic carriers. These observations suggest that a factor (or factors) may be correlated at least partially with the induction of the asymptomatic carrier state, such as unresponsiveness to the estrogen. PMID- 4040492 TI - Prospective payment: the vital role of research. PMID- 4040493 TI - A plan for prospective payment for inpatient psychiatric care. PMID- 4040494 TI - Nutrition and immunity: the immunoregulatory effect of n-6 essential fatty acids is mediated through prostaglandin E. AB - Suppression of cell-mediated immune responses by essential fatty acids (EFA) was demonstrated in mice maintained on a standard laboratory diet for rodents. Daily oral administration of EFA at doses ranging from 125 to 750 mg/kg body weight significantly suppressed local host-versus-graft and graft-versus-host reactions as measured by popliteal lymph node assay. Studies employing immune sera directed against E-type prostaglandin demonstrated that n-6 EFA-induced suppression was mediated through prostaglandin E1. In titration experiments the effect of n-6 EFA on the reactions was dose dependent with enhancement of the responses at low concentrations and suppression at high concentrations. PMID- 4040495 TI - Changes in intratesticular testosterone, cytoplasmic androgen receptors and ABP content of the ram testis after a single endogenous pulse of LH. AB - The effects of an endogenous LH pulse on the testicular concentration of testosterone, cytoplasmic androgen receptor content and androgen binding protein (ABP) content was studied in rams. Blood was collected from 36 rams for at least 14 h and their testes then removed. Animals were then grouped according to the interval from their last LH pulse and the time of slaughter. The concentration of testosterone in the testis was highest during the first h following the LH pulse and returned to its baseline within 5 h. There was a 60% reduction in the testicular content of cytoplasmic androgen receptors at 3 h after the LH pulse, followed by slow replenishment. The testicular content of ABP was highest at 4 h after the LH pulse. It is in the testis concluded that the pulsatility of LH and testosterone induces a pulsatile translocation of cytoplasmic androgen receptors. PMID- 4040496 TI - Serum micronutrient levels in relation to gastric pathology. AB - As part of an ongoing cohort study of gastric cancer precursors in Narino, Colombia, blood levels of ascorbic acid, vitamin E, retinol, pre-albumin, retinol binding protein and carotenoids were measured and correlated with histopathologic findings of gastric biopsies. Carotene levels in both sexes and vitamin E levels in males were significantly lower in subjects with gastric dysplasia than in subjects with normal mucosa and subjects with less advanced gastric lesions (chronic atrophic gastritis and intestinal metaplasia). No other significant correlations were found. PMID- 4040497 TI - Case control study of cervical cancer in Herrera Province, Republic of Panama. AB - A previous survey found the average annual age-adjusted incidence of cervical cancer in Herrera Province, Panama, to be 79/100,000, exceeding any other reported world rate. In an effort to clarify the reasons for this excessive occurrence, a case-control study was conducted among patients diagnosed between 1974-1980. Sixty-six percent of cervical cancer patients from Herrera Province were alive and were contacted by the study team; of these 91% were successfully interviewed and provided serum specimens. The total study encompassed 156/169 surviving patients and 309 age-neighborhood matched controls. Sexual promiscuity was uncommon, but it exerted a major effect, with those reporting 4 or more life time sex partners being at a 4-fold excess risk compared to those reporting only one partner. First intercourse at a young age was common (21% began sexual activity prior to age 16) but it failed to alter risk once number of partners was taken into account. Oral contraceptive use was associated with a 2-fold excess risk and this was not substantially affected by controlling for sexual parameters. Thirty-three percent of the study subjects had anti-herpes-simplex type-2 antibody as measured by both neutralization and radioimmunoassays. Although results of the neutralization test were not predictive of risk, women with a radioimmunoassay indicative of HSV-2 infection were at a 40% excess risk for cervical cancer after adjustment for sexual characteristics. PMID- 4040498 TI - The establishment and characterization of a new BALB/c angiosarcoma tumor system. AB - A BALB-3T3/A31 untransformed cloned cell line and 3 selected variants derived from this parental cell line, expressing 3 increasingly malignant phenotypes, have been established and characterized in vivo and in culture. This new tumor series, identified as angiosarcoma, consists of an anchorage-independent non tumorigenic cell clone and 2 sublines exhibiting tumorigenic and metastatic properties. Morphological examination revealed that the 3 transformed cell variants differed from the normal parental cells and were not contact-inhibited. Karyotype and rate of cell proliferation in culture were similar for all the cell variants. Cytoskeletal visualization by immunofluorescence staining revealed that the tumorigenic and metastatic cell lines expressed an altered organization of actin cables and a smaller number of vinculin-containing focal contacts. Lactoperoxidase iodination of cell surface proteins showed the appearance of an Mr 86,000 protein in the tumorigenic and metastatic cell variants. Analysis of cell-surface glycoproteins demonstrated an increased sialylation of Mr 66,000 and Mr 62,000 glycoproteins in the transformed, tumorigenic and metastatic cell lines. This angiosarcoma tumor model system allows investigation of cellular characteristics which might be relevant to specific stages in tumor progression. PMID- 4040499 TI - Longitudinal changes in left ventricular diastolic function in hypertrophic cardiomyopathy. AB - Digitised M-mode echocardiography was used to study the changes in left ventricular diastolic function over a 3-year period in 11 patients with hypertrophic cardiomyopathy an 14 normals. Compared to normal, in hypertrophic cardiomyopathy, isovolumic relaxation was prolonged (P less than 0.001) and mitral valve opening delayed relative to minimum dimension (P less than 0.001). There was a wide range of values for the peak rates of dimension increase and wall thinning, and although the means were normal, 6 and 8 patients respectively were outside the normal range. There were no significant mean changes in function during the 3.4 +/- 0.3 years of follow-up, but, in 3 patients, marked alterations in relaxation were observed. They showed a gross reduction in the delay in mitral valve opening (125 to 55 125 to 35 and 110 to 75 msec). There was little overall change in isovolumic relaxation in two, but in one patient it reduced from 95 to 50 msec. In most patients with hypertrophic cardiomyopathy, relaxation and diastolic function appear to remain stable over a period of 3 years, and none had an apparent deterioration. Some patients may have an apparently spontaneous "improvement" in function similar in extent to that described due to the therapeutic action of calcium antagonists. PMID- 4040500 TI - Augmented thromboxane A2 generation and efficacy of its blockade in acute myocardial infarction. AB - Serial changes in thromboxane B2, a stable catabolite of thromboxane A2, were measured by radioimmunoassay in peripheral plasma of 55 patients with acute myocardial infarction. Twenty two of 31 patients who were admitted within 6 hr after the onset of acute myocardial infarction, exhibited high thromboxane B2 levels (greater than 300 pg/ml plasma) during the first 24 hr, whereas thromboxane B2 levels of 9 patients never exceeded 300 pg/ml during that period. The former cases were associated with a higher frequency of transmural myocardial infarction, accompanying higher cumulative creatine kinase release (1173 +/- 134 mIU/ml, mean +/- SEM), as compared with the latter cases (393 +/- 104 mIU/ml, P less than 0.001). To evaluate the efficacy of selective thromboxane A2 blockade on diminution of propagating acute myocardial infarction, another group of patients (24 cases) showing transmural myocardial infarction were subjected to therapeutic examination employing OKY-1581, a potent thromboxane A2 synthetase inhibitor. Eleven randomly selected patients were treated with an infusion of OKY 1581 (initiated within 6 hr after onset, 2-3 micrograms/kg per min) for 48 hr, while 13 patient served as controls. The treated patients exhibited a precipitous decrease in thromboxane B2 levels, as compared with the controls, returning to the normal range within 12 hr. The creatine kinase release in the treated patients was markedly reduced (978 +/- 97 mIU/ml) as compared with that in the control patients (1295 +/- 95 mIU/ml, P less than 0.05). These results indicate that a marked increase in thromboxane B2 levels is seen during the early phase of transmural myocardial infarction, and that OKY-1581-induced reduction of thromboxane B2 levels is effective in diminishing creatine kinase release. We suggest that an excessive generation of thromboxane A2 is associated with the evolution of transmural myocardial infarction. PMID- 4040501 TI - Myocardial bridging and hypertrophic cardiomyopathy: relief of ischemia by surgery. AB - We describe a case of myocardial bridging of the anterior descending coronary artery associated with a non-obstructive hypertrophic cardiomyopathy which was corrected by surgery because of a poor response to standard drug therapy. The clinical significance of the association is discussed. The possibility of repair by surgery should be considered when an area of ischemia supplied by the affected vessel is detected and previous medical treatment has been ineffective. PMID- 4040502 TI - Haemangiosarcoma of bone. AB - Haemangiosarcoma of bone is a very rare primary tumour with a variable history and differing radiographic and histological appearances. In some cases the lesion has similar features to the so-called "adamantinoma of long bones" in which the histogenesis is also unknown. Such a lesion is described which occurred in the shaft of the right humerus of a 31-year-old man. Radiographically a centrally located area of osteolysis was seen without marginal sclerosis, but with erosion of the bony cortex. A biopsy was performed 16 months after the first radiographic examination and showed malignant tumour tissue which was difficult to classify histomorphologically. Several different neoplasms such as Ewing's sarcoma, myeloma, liposarcoma, malignant fibrous histiocytoma or a bone metastasis were suggested. Finally, a haemangiosarcoma or so-called "adamantinoma of long bones" was considered. The tumour was completely removed by en-bloc resection. Careful histomorphological investigation of the tumour tissue by means of light microscopy, cytology and electronmicroscopy showed a vascular pattern characteristic of a haemangiosarcoma. Using cytophotometric DNA measurements of the tumour cells, the lesion could be classified as being of low-grade malignancy. This is confirmed since there has now been a 4-year follow up with no local recurrence or metastasis. There are many similarities between a well differentiated haemangiosarcoma and an "adamantinoma of long bones". The differential diagnosis and the histogenesis of the latter lesion is discussed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4040503 TI - Self-envy, the womb and the nature of goodness. A reappraisal of the death instinct. AB - The Freudian and Kleinian conceptions of the struggle between 'life' and 'death' instincts are not identical. This paper puts forward a model which attempts both to reconcile and add to the differences between them, whilst making some suggestions about the 'nature of goodness'. Attention is focused on the phantasy of returning to the womb and its consequent anxieties to the growing, active ego. Such anxiety, and its reverse, can only be moderated by the introjection of an object which is capable of creatively resolving the resulting conflicts. When envious feelings are not tolerated the impetus for such an introjection is reduced, which, in turn, increases the envy. PMID- 4040504 TI - Interaction between ascorbic acid and acetylsalicylic acid and their effects on nutritional status in man. AB - Healthy adults were given four diets, each one for one week: Low ascorbic acid diet, low ascorbic acid diet plus acetylsalicylic acid (3 g/d), high ascorbic acid diet (1 g/d) and high ascorbic acid diet plus acetylsalicylic acid. At low ascorbic acid intake, acetylsalicylic acid increased urinary ascorbic acid, but at high ascorbic acid intake, acetylsalicylic acid instead decreased urinary ascorbic acid. The latter effect was probably due to an inhibited intestinal absorbtion of ascorbic acid, and the former effect may reflect decreased protein binding and tissue uptake of ascorbic acid caused by acetylsalicylic acid. In no instance, acetylsalicylic acid affected plasma ascorbic acid. The effect of ascorbic acid on substances related to lipid peroxidation was investigated. The high ascorbic acid diets decreased plasma lipoperoxide and retinol binding protein. No change was observed in serum tocopherol, iron status, erythrocyte lipid fluorescence, plasma ceruloplasmin, urinary and plasma selenium and glutathione peroxidase activity. Thus, one-week supplementation of ascorbic acid seems to have only marginal effects on lipid peroxidation and antioxidant status. PMID- 4040506 TI - Use of danazol in the management of chronic idiopathic thrombocytopenic purpura. AB - Danazol, an impeded androgen, was used for treating three patients with chronic idiopathic thrombocytopenic purpura (ITP) refractory to corticosteroid therapy. Sustained remission was achieved in one of the three cases. A temporary response was obtained in the second patient. In the last case, platelet count improved, but the patient died of severe interstitial pneumonitis. These observations confirm recent reports on the efficacy of danazol in the management of ITP and indicate that danazol treatment improves platelet counts in the majority of patients with refractory ITP, and in some cases may obviate the need for splenectomy. PMID- 4040505 TI - Pharmacology of mitoxantrone: mode of action and pharmacokinetics. AB - Although a number of investigators have established that mitoxantrone (Novantrone; dihydroxyanthracenedione) inhibits RNA and DNA synthesis and intercalates with DNA in vitro, its exact mechanism of action is unclear. Mitoxantrone is structurally related to a series of substituted anthraquinones and has features known to be essential for DNA intercalation; however, we have determined recently that mitoxantrone binds DNA in intact L1210 leukemia cells by a non-intercalative, electrostatic interaction and induces both protein associated and non-protein associated DNA strand scissions. The difference between mitoxantrone and doxorubicin with respect to their interactions with DNA could account for their relative lack of cross-resistance in the treatment of lymphoma and acute leukemia. Distribution and half-life data provide a pharmacological rationale for the use of mitoxantrone on an intermittent dosing schedule. Considerable evidence exists to suggest that mitoxantrone undergoes extensive metabolism, probably in the liver. Preliminary data show that abnormal liver function leads to decreased rates of total body mitoxantrone clearance, suggesting a possible need for dose reduction in patients with severe liver dysfunction. The most important route of mitoxantrone elimination appears to be fecal. Because of the relatively low urinary excretion it is unlikely that the standard drug dose must be reduced in the presence of compromised renal function. PMID- 4040507 TI - The effect of 1 alpha-hydroxyvitamin D3 on primary antibody formation in mice. AB - The immunoregulatory effect of 1 alpha-hydroxyvitamin D3, a precursor form of active vitamin D3 (1,25-dihydroxyvitamin D3), was examined in three different kinds of experimental systems in mice. Oral administration of 0.05 and 0.2 micrograms/kg of 1 alpha-hydroxyvitamin D3 augmented the primary immune response induced by immunization with 1 X 10(7) sheep erythrocytes, although it did not influence a maximal level of antibody formation induced by immunization with 5 X 10(8) sheep erythrocytes. The same treatment also restored the immune response depressed by restraint-stress. Furthermore, 1 alpha-hydroxyvitamin D3 suppressed the anti-dinitrophenyl plaque-forming cell response enhanced by colchicine injection to near the normal level. These results suggest that 1 alpha hydroxyvitamin D3 enhanced or suppressed the immune response through activating helper and suppressor cells in dependence on the magnitude of the response. PMID- 4040508 TI - Immunosuppression by polycyclic aromatic hydrocarbons: a structure-activity relationship in B6C3F1 and DBA/2 mice. AB - The structure-activity relationship of polycyclic aromatic hydrocarbon-induced immunosuppression was investigated using the antibody-forming cell response to sheep erythrocytes. Ten polycyclic aromatic hydrocarbons were evaluated following 14 days of subchronic exposure in female B6C3F1 mice. Additionally, the immunotoxicity of benzo(a)pyrene and 3 of its congeners was evaluated following acute exposure. The immunosuppression observed following both subchronic and acute exposure was similar to the structure-activity relationship observed for the carcinogenicity of the compounds tested. Anthracene, chrysene, benzo(e)pyrene and perylene did not significantly suppress the antibody-forming cell response compared to the corn oil vehicle controls. Benz(a)anthracene, benzo(a)pyrene, dibenz(a,c)anthracene, and dibenz(a,h)anthracene suppressed the antibody-forming cell response by 55 to 91%. The greatest suppression was observed with the 3 methylcholanthrene and 7,12,-dimethylbenz(a)anthracene. Studies using mice with different susceptibility to aryl hydrocarbon hydroxylase induction demonstrated that susceptible mice (B6C3F1) were not as immunosuppressed following exposure to polycyclic aromatic hydrocarbons as were nonsusceptible mice (DBA/2). PMID- 4040509 TI - Presumptive neonatal isoerythrolysis in cats. AB - Entire or partial litters of 4 queens died due to hemolytic anemia within 1 to 2 days of birth. Necropsy and histologic examination of tissues from 6 dead kittens were indicative of neonatal isoerythrolysis. Blood samples from affected kittens were not available for study. Nevertheless, hemolysins and agglutinins in each queen's serum reacted with RBC from 2 sires of the affected litters. These antibodies, identified as anti-A, also reacted with the RBC from 64 random-source cats. PMID- 4040510 TI - Microbial hydroxylation of compactin (ML-236B) and monacolin K. AB - The Basidiomycete Schizophyllum commune was found to transform compactin (ML 236B) to 8a-hydroxycompactin. This compound was isolated by solvent extraction and column chromatography, and its structure was determined by a combination of IR, UV, 1H NMR and 13C NMR spectroscopy. Monacolin K was also converted to the corresponding hydroxylated analogue. Data on the inhibition of 3-hydroxy-3 methylglutaryl co-enzyme A reductase and sterol biosynthesis in vitro are presented for these hydroxylated compounds. PMID- 4040511 TI - Onset of puberty and duration of the breeding season in Suffolk, Rambouillet, Finnish Landrace, Dorset and Finn-Dorset ewe lambs. AB - Sixty ewe lambs, 12 each of Suffolk, Dorset, Finnish Landrace, Finn-Dorset and Rambouillet born in January and February were used in a study of puberty and duration of the first breeding season. Ovulation was monitored via progesterone assay of weekly blood samples beginning in July, and estrus via daily checking with vasectomized rams. All 60 ewes ovulated but three, one Dorset and two Rambouillet failed to show estrus although each had five to seven ovulatory cycles. Several ewes showed small progesterone rises, 300 to 500 pg/ml, before first ovulation and six (10%) failed to initiate regular cyclicity following the first ovulation as defined by progesterone greater than 500 pg/ml. Mean number of ovulatory events before the first behavioral estrus ranged from 1.25 for Finnish Landrace to 2.20 for Rambouillet ewe lambs (P less than .1). Rambouillets were older (277 d; P less than .05) at first estrus than Finns (258 d) and Finn Dorsets (260 d), but differences in age at first ovulation were not significant: Finn-Dorset, 233 d; Dorset, 234 d; Finn, 235 d; Rambouillet, 240 d; Suffolk, 245 d. Most cycles were of normal length, with 91.4% between 14 and 20 d. Repeatability of cycle length within breed group was .38. Suffolks had significantly shorter cycles (16.1 d) than the other four groups (17.0 to 17.4 d). Finnish Landrace and Finn-Dorset ewes continued to cycle much longer than the other groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4040512 TI - Occurrence and characteristics of sclerotic lesions in uterine arteries of sterile and multiparous pigs. AB - Sows and gilts of the Great White Polish (GWP) breed were classified into groups of 10 each: gilts 8 mo of age (A), sows over 1 yr old with an average litter size of five (BI) and eleven (BII), 2- to 3-yr-old sows with an average litter size of five (CI) and nine (CII), 4- to 6-yr-old sows with an average litter size of six (DI) and nine (DII). Gilts of group A were necropsied on d 10 of the estrous cycle while sows were necropsied 120 to 360 d postpartum. A blood sample obtained by vena cava puncture immediately before exsanguination was quantitated for total cholesterol, free cholesterol, cholesterol ester, total lipid, triglyceride, high and low density lipoprotein and chylomicrons. Postmortem angiograms of the uterine vasculature were evaluated for occurrence of arteriosclerotic lesions of the arteries and their branches. Sections of blood vessels from areas of restriction were examined histologically and quantitated for lipids and proteolytic and lipolytic enzyme activities. With the exception of high density lipoproteins and chylomicrons, serum concentrations of various lipids increased (P less than .01) with age. Restrictions of the lumen were found in uterine arteries and their branches of most gilts in group A and in sows in groups B, C and D, irrespective of litter size. Histology of uterine artery revealed preatherosclerotic lesions in groups B through D. No relationship between the incidence and degree of sclerotic lesions and litter size was evident. However, the incidence and degree of sclerotic lesions increased with age and parity. Results from histopathology were supported by results from measurement of lipids and enzyme activities of the uterine artery wall. Conception rates of sows in groups C and D were lower than those of group B. Many of these sows (70%) failed to conceive during 1 yr even though they displayed normal estrous cycles. PMID- 4040513 TI - Microencapsulation of bovine spermatozoa. AB - Two experiments were conducted to examine the efficacy of microencapsulation of bovine spermatozoa for use in artificial insemination. In Exp. 1, sperm were encapsulated at three different concentrations (45, 90 and 180 X 10(6) sperm/ml) in either .75- or 1.5-mm (diameter) microcapsules and incubated in vitro for 24 h at 37 C. Unencapsulated samples of each concentration served as controls. Capsule contents were evaluated for percentage of sperm motility and intact acrosomes at 2, 12 and 24 h of incubation. Capsule fragility was evaluated after 24 h incubation. Viability of spermatozoa was not influenced by sperm concentration or capsule size, and compared with controls, cellular injury after encapsulation was not apparent. Fragility of capsules was unaffected by capsule size; however, as the sperm concentration increased, integrity of the capsules decreased (P less than .05). In Exp. 2, using frozen-thawed semen, the effect of egg yolk content, presence of glycerol and viability of spermatozoa on the success of microencapsulation was measured. The extender was 2.9% sodium citrate with glycerol (7% v/v) and either 0, 5, 10 or 15% egg yolk (v/v). Uniformity of capsules in size and shape was evaluated subjectively. Capsule integrity and uniformity were unaffected by glycerol, sperm viability or egg yolk level up to 10% v/v; however, encapsulation of spermatozoa in 15%-yolk buffer increased the heterogeneity in capsule size and shape. Viability of encapsulated spermatozoa was maximal for extenders containing 10 or 15% yolk v/v. Reduced viability for the 5% yolk extender was due to pre-encapsulation injury associated with freezing. Microencapsulation procedures are compatible with sperm viability and can be adapted to an acceptable extender system used in artificial insemination. PMID- 4040514 TI - Liquid chromatographic determination of 2-(2-quinolinyl)-1H-indene-1,3-[2H]-dione and other organic-soluble matter in D&C Yellow No. 10. AB - A sensitive, reproducible method that uses an Extrelut QE column and liquid chromatography (LC) in the reverse phase mode is described for the determination of 2-(2-quinolinyl)-1H-indene-1,3-[2H]-dione and other organic-soluble matter found in D&C Yellow No. 10. With this method the organic-soluble matter is extracted from D&C Yellow No. 10 on an Extrelut QE column, and the extract is concentrated and analyzed by LC. Recoveries averaged 104% for 2-(2-quinolinyl)-1H indene-1,3-[2H]-dione added to purified D&C Yellow No. 10 at levels ranging from 0.50 to 5.96 ppm. PMID- 4040515 TI - Bovine mitochondrial ribosomes. Elongation factor specificity. AB - The activity of bovine mitochondrial ribosomes with elongation factors from a variety of sources including the mitochondria of lower eukaryotes, chloroplasts, Gram-negative bacteria, Gram-positive bacteria, and the eukaryotic cell cytoplasm has been investigated. Bovine mitochondrial ribosomes are active with homologous mitochondrial elongation factor (EF)-G but display no activity with the mitochondrial or chloroplast translocases from the lower eukaryote Euglena gracilis, with Escherichia coli or Bacillus subtilis EF-G or with cytoplasmic EF 2. In contrast to the results obtained with the translocases, E. coli EF-Tu, B. subtilis EF-Tu, and Euglena chloroplast EF-Tu all function to a significant extent on the mitochondrial ribosomes. Cytoplasmic EF-1 has barely detectable activity on the animal mitochondrial ribosomes. The polymerization of phenylalanine by these ribosomes is dependent on poly(U), displays a rather broad Mg2+ optimum around 12 mM, and proceeds most rapidly at low monovalent ion concentrations. PMID- 4040516 TI - Dynamics of dioxygen and carbon monoxide binding to soybean leghemoglobin. AB - The association of dioxygen and carbon monoxide to soybean leghemoglobin (Lb) has been studied by laser flash photolysis at temperatures from 10 to 320 K and times from 50 ns to 100 s. Infrared spectra of the bound and the photodissociated state were investigated between 10 and 20 K. The general features of the binding process in leghemoglobin are similar to the ones found in myoglobin. Below about 200 K, the photodissociated ligands stay in the heme pocket and rebinding is not exponential in time, implying a distributed enthalpy barrier between pocket and heme. At around 300 K, ligands migrate from the solvent through the protein to the heme pocket, and a steady state is set up between the ligands in the solvent and in the heme pocket. The association rate, lambda on, is mainly controlled by the final binding step at the heme, the bond formation with the heme iron. Differences between Lb and other heme proteins show up in the details of the various steps. The faster association rate in Lb compared to sperm whale myoglobin (Mb) is due to a faster bond formation. The migration from the solvent to the heme pocket is much faster in Lb than in Mb. The low-temperature binding (B----A) and the infrared spectra of CO in the bound state A and the photodissociated state B are essentially solvent-independent in Mb, but depend strongly on solvent in Lb. These features can be correlated with the x-ray structure. PMID- 4040517 TI - Turnover and short-term regulation of fatty acid binding protein in liver. AB - Rat hepatic fatty acid binding protein (hFABP) may play an important role in the intracellular transport and metabolism of fatty acids. Recent reports have suggested a substantial circadian variation in the amount of hFABP in liver, and a half-life of less than 2 h for this protein has been inferred. In the present study, the kinetics of hFABP turnover were examined directly. hFABP half-life measured after pulse labeling with NaH14CO3 was 3.1 days compared with 2.9 days for total cytosol protein. Following double-isotope labeling, the charge isoforms of hFABP showed similar rates of turnover, all of which were slower relative to whole cytosol protein turnover. Following a 48-h fast, total liver hFABP measured by immunoassay fell 65%, paralleling a 60% fall in total cytosol protein. Refeeding for 24 h did not lead to a significant recovery of either hFABP or total cytosol protein content. No significant change was observed in hFABP abundance between mid-light and mid-dark periods of a 24-h light-dark cycle. These studies showed that hFABP has a relatively slow rate of turnover and that it is not acutely modulated by dietary or diurnal influences. PMID- 4040518 TI - Identification of two alpha-ketoglutarate-dependent dioxygenases in extracts of Rhodotorula glutinis catalyzing deoxyuridine hydroxylation. AB - Attempts to isolate deoxyuridine 2'-hydroxylase from Rhodotorula glutinis by the procedure of Warn-Cramer et al. (Warn-Cramer, B. J., Macrander, L. A., and Abbott, M. T. (1983) J. Biol. Chem. 258, 10551-10557) have led to the identification and partial purification of a newly recognized alpha-ketoglutarate requiring oxygenase. This activity, designated deoxyuridine (uridine) 1' hydroxylase, in the presence of iron and ascorbate, catalyzes the conversion of deoxyuridine (uridine), O2, and alpha-ketoglutarate to uracil, deoxyribonolactone (ribonolactone), CO2, and succinate. Incubation of [1'-3H]uridine with this activity results in time-dependent formation of uracil concomitant with production of CO2 and 3H2O. No Vmax/Km isotope effect is observed on this reaction. Uracil production is accompanied by stoichiometric production of ribonolactone identified by NMR spectroscopy. Also reported in this paper is the partial purification and characterization of the alpha-ketoglutarate-requiring enzyme, deoxyuridine 2'-hydroxylase. Incubation of [2'-alpha-3H]deoxyuridine with this activity results in concomitant production of uridine and 3H2O. Incubation with [2'-beta-3H] deoxyuridine results in the production of uridine whose specific activity is identical to that of the starting material. This enzyme catalyzes the conversion of deoxyuridine to uridine with retention of configuration. No isotope effect is observed on this transformation. PMID- 4040519 TI - Intracellular transport of phosphatidylcholine to the plasma membrane. AB - We have used pulse-chase labeling of Chinese hamster ovary cells with choline followed by plasma membrane isolation on cationic beads to study the transport of phosphatidylcholine from the endoplasmic reticulum to the plasma membrane. We have found that the process is rapid (t1/2 [25 degrees C] = 2 min) and not affected by energy poisons or by cytochalasin B, colchicine, monensin, or carbonyl cyanide p-chlorophenylhydrazone. Cooling cells to 0 degree C effectively stops the transport process. The intracellular transport of phosphatidylcholine is distinct in several ways from the intracellular transport of cholesterol (Kaplan, M. R., and R. D. Simoni, 1985, J. Cell. Biol., 101:446-453). PMID- 4040520 TI - Transport of cholesterol from the endoplasmic reticulum to the plasma membrane. AB - We have studied the transport of newly synthesized cholesterol from the endoplasmic reticulum to the plasma membrane in Chinese hamster ovary cells using a cell fractionation assay. We found that transport is dependent on metabolic energy, but that the maintenance of the high differential concentration of cholesterol in the plasma membrane is not an energy-requiring process. We have tested a variety of inhibitors for their effect on cholesterol transport and found that cytochalasin B, colchicine, monensin, cycloheximide, and NH4Cl did not have any effect. The cholesterol transport process shows a sharp temperature dependence; it ceases at 15 degrees C, whereas cholesterol synthesis continues. When synthesis occurs at 15 degrees C, the newly synthesized cholesterol accumulates in the endoplasmic reticulum and in a low density, lipid-rich vesicle fraction. These results suggest that cholesterol is transported via a vesicular system. PMID- 4040522 TI - Effects of sulphydryl reagents on the structure of dehistonized metaphase chromosomes. AB - Dehistonized metaphase chromosomes lose their apparent axial organization (the 'scaffold') and sediment more slowly following exposure to beta-mercaptoethanol (BME). We have subsequently treated BME chromosomes with reagents that oxidize protein sulphydryls to disulphides, and found that if calcium is also present during the oxidation an apparently similar axial structure is restored following dehistonization, as seen by microscopic examination. In general, however, we do not find that oxidation restores the higher sedimentation rate of dehistonized control chromosomes. Analysis of residual core protein in dehistonized chromosomes by sodium dodecyl sulphate/polyacrylamide gel electrophoresis fails to detect any differences in polypeptide composition related to the state of oxidation or to the presence or absence of visible axial organization. Combining our results with those of other workers, we conclude that the axial structure evident in dehistonized metaphase chromosomes is maintained, at least partially, by inter-protein cross-linking, although in vivo this may not be via simple disulphide bridges. Additional factors, which we have not yet characterized, but which possibly include heavy metal ions, appear to be involved in the axial organization existing in vivo. PMID- 4040521 TI - Exchange of actin subunits at the leading edge of living fibroblasts: possible role of treadmilling. AB - Previous observations indicated that the lamellipodium ("leading edge") of fibroblasts contains a dense meshwork, as well as numerous bundles (microspikes) of actin filaments. Most, if not all, of the filaments have a uniform polarity, with the "barbed" end associated with the membrane. I investigated whether and how actin subunits exchange in this region by microinjecting living gerbil fibroma cells (IMR-33) with actin that had been labeled with iodoacetamidotetramethylrhodamine. After incorporation of the labeled actin into the lamellipodium, I used a laser microbeam to photobleach a 3-4-micron region at and surrounding a microspike, without disrupting the integrity of the structure. I then recorded the pattern of fluorescence recovery and analyzed it using a combination of TV image intensification and digital image processing techniques. Fluorescence recovery was first detected near the edge of the cell and then moved toward the cell's center at a constant rate of 0.79 +/- 0.31 micron/min. When only part of the lamellipodium near the edge of the cell was photobleached, the bleached spot also moved toward the cell's center and through an area unbleached by the laser beam. These results indicated that steady state incorporation of actin subunits occurred predominantly at the membrane-associated end of actin filaments, and that actin subunits in the lamellipodium underwent a constant movement toward the center of the cell. I suggest that treadmilling, possibly in combination with other molecular interactions, may provide an effective mechanism for the movement of actin subunits and the protrusion of cytoplasm in the lamellipodium of fibroblasts. PMID- 4040523 TI - Ultrastructural analysis of the initiation and development of cytasters in sea urchin eggs. AB - Two approaches were used to study the origin and overall development of cytasters in relation to the emergence and maturation of new centrioles in sea-urchin eggs. A continuous hypertonic treatment was used to gather information on cytoplasmic areas of potential cytaster formation and the subsequent development of these cytastral areas. A two-step parthenogenetic stimulation procedure was used to analyse various cytastral changes during and after mitosis. Potential cytastral areas are associated with extensive Golgi complexes and astral formation occurs only about newly induced centrioles. The construction of a single aster involves a large redistribution of local cytoplasmic structures, concentrating some components, excluding others and orienting more and more microtubules in an increasingly focussed arrangement. These events are correlated with an extensive accumulation of astral endoplasmic reticulum, an increase in the size of the astral area, and a gradual acquisition of a more typical radial configuration. The astral shape becomes more pronounced during mitosis, after which the cytasters regress, but retain the mature centrioles. The data reveal that cytaster formation is initiated after the activation and appearance of centriolar precursor bodies, and that both centrioles and associated cytasters are complementary structures, which develop in unison. The results suggest that developing centrioles, from the moment of their emergence, control and direct the events of cytastral formation. PMID- 4040524 TI - The specificity and stability of the triton-extracted cytoskeletal framework of gerbil fibroma cells. AB - Cellular meshworks and topography of gerbil fibroma cells can be preserved by gentle extraction procedures using Triton X-100. We determined the stability and specificity of these cytoskeletal frameworks by measuring extraction rate and its sensitivity to exogenous protein. Two buffers were used, which mimicked the intracellular and extracellular ionic environments. With both buffers, extraction was nearly complete at 5 min. This pattern of extraction was seen both in 5- and 9-day-old cultures. The same pattern of extraction was seen when three different dilutions of cells were examined the second day after plating. Thus, extraction rate was largely independent of minor variations in ionic composition, age in culture, or cell density. Specificity of the cytoskeletal frameworks so produced was determined by competition with two different exogenous proteins (bovine serum albumin or ovalbumin), which did not remove any additional material from the cytoskeletal frameworks, even with over 10% exogenous protein in the extraction buffer. This pattern of extraction is not unique to gerbil fibroma cells. A similar pattern of extraction was seen for a series of cells: mouse 3T3 cells, 3T6 cells and SVPY 3T3 cells. These experiments indicate that the cytoskeletal framework produced by Triton extraction under appropriate conditions is stable after extraction for a period of 10 min or longer, and that the structures are specific, in that they are not disrupted by the presence of exogenous proteins. PMID- 4040525 TI - Glycogen metabolism and the nuclear envelope-annulate lamella system in the early chick embryo. AB - The intracellular sites of glycogen degradation in the mid to late uterine chick embryo were determined by cytochemical localization of glucose-6-phosphatase at the ultrastructural level. Enzyme activity was found between the two membranes of the nuclear envelope, in the annulate lamellae and in specialized glycogen containing membrane scrolls. Annulate lamellae and glycogen scrolls were most frequent during the stages of intensive glycogen degradation. Annulate lamellae appear to be formed from the nuclear envelope. During the early post-laying stages annulate lamellae disappeared and were replaced by endoplasmic reticulum that appeared initially in scroll-like formations. PMID- 4040526 TI - Analysis of soybean sapogenins by high-performance liquid chromatography. AB - A method for the analysis of soybean sapogenins is described. The method is based on the extraction of soybean saponins from a defatted sample. The triterpene glycosides are then hydrolysed with subsequent analysis of the liberated sapogenins by high-performance liquid chromatography using gradient elution and mass detection. By use of a sapogenin/carbohydrate ratio, an estimate of the total saponin content can be made. PMID- 4040527 TI - Determination of homocysteine in urine. PMID- 4040528 TI - Reversed-phase high-performance liquid chromatographic separation of molecular species of alkyl ether, vinyl ether, and monoacyl lysophospholipids. AB - An isocratic reversed-phase high-performance liquid chromatographic method was developed which resolved individual molecular species of choline and ethanolamine lysophospholipids utilizing a C13 bonded porous silica stationary phase with a mobile phase comprised of methanol--water--acetonitrile (57:23:20) containing 20 mM choline chloride. Solute retention was primarily determined by hydrophobic interactions with the stationary phase permitting separation of individual molecular species of lysophospholipids according to the composition of the aliphatic chain and the nature of its covalent attachment to the sn-1 hydroxyl group. The elution profile of unsaturated monoacyllysophospholipid or lysoplasmalogen molecular species was readily obtained by measuring UV absorbance at 203 nm. Identification of column eluates containing saturated monoacyl and alkyl ether lysophospholipids was possible utilizing relative retention factors that were obtained for the majority of molecular species present in animal tissues. PMID- 4040529 TI - Aging alters somatomedin-C-dexamethasone synergism in the stimulation of deoxyribonucleic acid synthesis and replication of cultured human fibroblasts. AB - The effects of dexamethasone on somatomedin-C (SM-C) stimulation of [3H]thymidine incorporation and cell replication were studied in early passage fibroblasts from normal donors, aged 7-24 yr (young) and 85-96 yr (old), and one patient with progeria. Preincubation of cells from young donors with dexamethasone dramatically enhanced SM-C stimulation of [3H]thymidine incorporation [e.g. 19- vs. 3-fold in serum-free medium; 66- vs. 14-fold in 0.25% human hypopituitary serum (HHS)], with no alteration in the timing of peak thymidine incorporation. In contrast, preincubation of cells from old and progeric donors with dexamethasone resulted in a 6- to 12-hr lengthening of the prereplicative period and, generally, little or no synergism with SM-C. Cells from old and progeric donors had a normal replicative response to SM-C with or without 0.25% HHS. In cells from young donors, dexamethasone enhanced the SM-C-stimulated increase in cell number 32-49% in serum-free medium and 70-189% in 0.25% HHS. In comparison, dexamethasone had no potentiating effect on SM-C stimulation of multiplication of cells from old and progeric donors. These data indicate that dexamethasone and SM C are synergistic in stimulating DNA synthesis and replication of fibroblasts from young donors, but that this synergism is impaired in cells from aged and progeric donors. PMID- 4040530 TI - Somatotropic adenoma manifested by galactorrhea without acromegaly. AB - In two of eight premenopausal women with somatotropic adenomas, galactorrhea was the earliest clinical feature, associated in one patient with amenorrhea. These two patients did not have clinically evident acromegaly. Mean basal serum GH levels were elevated and did not decrease after glucose ingestion. Both patients had modest hyperprolactinemia. Histological and immunocytological studies of the adenomas showed numerous adenomatous somatotropic cells and some alpha-subunit- and PRL-containing cells. In these patients, the origin of the hyperprolactinemia was not clear. In one patient, elevated GH secretion was probably responsible for the galactorrhea, since it disappeared after surgical treatment despite persistence of hyperprolactinemia. In conclusion, galactorrhea, isolated or associated with amenorrhea, can be the only clinical manifestation of a somatotropic adenoma. PMID- 4040532 TI - Antineurofilament antibody: an increased incidence in murine chronic measles encephalitis and the use of rat sciatic nerve sections as substratum. AB - Virus-associated autoimmune phenomena were investigated in the HNT-C57BL/6 chronic measles encephalitic mouse system. The incidence of serum antineurofilament autoantibodies was studied by an indirect immunofluorescence procedure using a FITC-conjugated goat anti-mouse immunoglobulin. Transversely cut cryostat sections of rat sciatic nerve post-treated with 1% Triton X-100 was used as substratum and had the advantages of increased reliability and reproducibility of neurofilament (NF) antibody titrations compared to the previously described longitudinal spinal cord sections. An increased incidence of anti-NF autoantibody was observed in sera from acutely, subacutely, chronically and asymptomatically infected mice compared to uninfected or mock-infected mice suggesting an association between the appearance of anti-NF antibody and HNT measles virus infection of the CNS. PMID- 4040531 TI - Transport of equine estrogens: binding of conjugated and unconjugated equine estrogens with human serum proteins. AB - The binding of ring B unsaturated equine estrogens, equilin sulfate (EqS), equilin (Eq), and 17 beta-dihydroequilin (17 beta-Eq) with human serum proteins was determined and compared with the binding of estrone sulfate (E1S), estrone (E1), estradiol (E2), testosterone (T), and 5 alpha-dihydrotestosterone (5 alpha DHT). Undiluted serum or 5% human serum albumin (HSA) was incubated with 3H labeled steroids at 37 C, then subjected to gel filtration at 4 C. Gel filtration of serum from Premarin-treated postmenopausal women or normal women incubated with Eq, E1, E2, or 5 alpha-DHT showed two peaks of radioactivity associated with proteins with average apparent mol wt of 128,000 and 68,000 and average Stokes radii of 48.6 and 34.9 A. These values correspond to those reported for sex hormone-binding globulin (SHBG) and albumin, respectively. Binding to SHBG and albumin was confirmed by removing SHBG or albumin from the serum with Concanavalin-A Sepharose 4B gel or CM-Affi Gel Blue, respectively. In the case of [3H]EqS and [3H]E1S, binding to SHBG was not detectable, and only a peak of radioactivity associated with albumin was found. However, under these conditions, the binding of estrogens to SHBG in serum from normal men was not detectable. Incubation of the above steroids with 5% HSA followed by gel filtration resulted in a single peak of radioactivity associated with the protein peak. Using ultrafiltration dialysis followed by Scatchard analysis, at least two sets of binding sites were found for the interaction of HSA with EqS or E1S. The high and low affinity binding sites had association constants k1 and k2 of approximately 0.9-1.1 (X 10(5) M-1) and 0.5-0.8 (X 10(4) M-1). In contrast with Eq and E1, only the low affinity binding sites were found (apparent Ka congruent to 1 X 10(4) M 1). The binding constants of some estrogens and androgens to SHBG at 37 C determined by competitive Scatchard analysis using DEAE filter assay and [3H]5 alpha-DHT were 0.15, 0.07, 0.22, 0.29, 2.70, and 4.53 (X 10(9) M-1) for Eq, E1, 17 beta-Eq, E2, T, and 5 alpha-DHT, respectively. These results indicate that the equine estrogens bind to SHBG and albumin in a manner similar to that of E1 and E2, and that the low MCR of EqS reported previously may be due to its binding to albumin. PMID- 4040533 TI - Effect of forskolin on phosphorylation of a 25,000 Mr protein in perfused guinea pig hearts. AB - The effects of forskolin on phosphorylation of proteins of a 100,000 X g fraction was examined in isolated beating guinea pig hearts. Hearts were perfused with [32P] inorganic phosphate to label intracellular adenine nucleotides. Forskolin was injected into the coronary circulation and after freeze-clamping, phosphorylated proteins in a fraction were separated by sodium dodecyl sulfate polyacrylamide gel electro-phoresis. Forskolin increased the incorporation into a 25,000 Mr protein approximately 15 fold over control. Incorporation of label was time and dose dependent and was temporally coincident with increases in developed tension. A sarcolemmal fraction prepared from perfused hearts contained a similar 25,000 Mr protein. The data provides evidence that forskolin induced inotropy is accompanied by cAMP-dependent protein kinase mediated phosphorylation. The phosphorylation may be of the same protein whose phosphorylation is associated with epinephrine-induced increase in contractility. PMID- 4040534 TI - High-oil, high-protein diets and milk secretion by cows. AB - Intakes of grass silage and yield and composition of milk were examined in cows given high-protein diets to which two quantities of soybean oil had been added either as intracellular or extracellular inclusions. Adding extra protein to the diet did not prevent reduction of dry matter intakes of forage when soybean oil was added to the diet of cows. There is a fundamental difference in the mechanism by which high-starch diets reduce intake of forage dry matter from that of high oil diets. In diets containing extracellular unsaturated oils, concentration of oil in the total ration, not the amount of oil per se, is the primary determinant reducing milk fat percentage. PMID- 4040535 TI - Diurnal temperature patterns of early lactating cows with milking parlor cooling. AB - Ten cows in early stages of lactation (less than 100 days postpartum) were used to test the effect of sprinkler/fan cooling on vaginal temperature patterns. Cows were assigned to two groups matched according to milk production. The trial was divided into three periods: period 1, when one group was treated and the other group was not, period 2, when neither group was treated, and period 3, when treatment was switched from period 1 between groups. Treatment consisted of forced air misting in a premilking holding pen, fan cooling during milking, and forced air-sprinkling in a postmilking holding area. Weather conditions were measured by dry bulb, wet bulb, and black globe temperatures. Black globe temperatures in pre- and postmilking holding areas were used to estimate treatment magnitude. All measures were obtained through radiotelemetry at 15-min intervals for 31 days. Animals were milked twice a day. Animals spent an average of 140 min in treatment at each milking. In both morning and afternoon milking, treatment caused a transient increase of body temperature. However, this was followed in the afternoon by low vaginal temperatures for 1 to 2 h beyond treatment with lower temperatures throughout the day. PMID- 4040537 TI - [Genetic model of stress-induced arterial hypertension]. PMID- 4040536 TI - [Synapses as the factors of integration potentials of the central nervous system]. PMID- 4040538 TI - The effect of chloride-containing potassium supplements on chloride titrator estimates of dietary sodium intake. AB - To examine the effect of chloride-containing potassium supplements on chloride titrator estimates of dietary sodium intake, we gave normal subjects diet containing 10, 100, or 200 mEq/d sodium in random order either as such, or supplemented with one of two potassium supplements. One regimen consisted of potassium 45 mEq/d with 12 mEq/d chloride and 33 mEq/d of citrate and gluconate; the other contained 48 mEq/d potassium and 48mEq/d chloride. Increased potassium intake with either supplemented regimen resulted in increased 24-hour potassium excretion, which was manifested in only the diurnal collections. Increased chloride intake resulted in increased urinary chloride excretion both during the day and at night. At all chloride intakes, urinary sodium and chloride excretion were highly correlated. The 48 mEq/d chloride intake generated a relationship with the same slope but with a different intercept from the other two regimens. The highest chloride intake resulted in a greater chloride titrator reading; however, the relationship was sufficiently predictable that adjustments in interpretation could be easily made. We conclude that if daily potassium chloride intake is known, chloride titrators continue to be reliable tools for estimating dietary sodium intake. PMID- 4040539 TI - [Glycosylated hemoglobin and monitoring of diabetic retinopathy]. AB - The value of glycosylated hemoglobin (HbA1) has been determined in diabetic patients with simple or proliferative retinopathy and in those without retinopathy. The mean value of HbA1 is significantly more highly elevated in patients with retinopathy than in those without retinopathy. Progressive augmentation of the value of HbA1 signifies a risk of deterioration of the retinopathy, whether it is a simple retinopathy or proliferative retinopathy. PMID- 4040540 TI - [Ovarian cancer 5 years after hysterectomy with adnexectomy for a benign lesion. Apropos of a case]. AB - The rare and strange evolution of an ovarian tumour in a woman of 58 years of age. Extraordinary in its method of presentation and interesting because of the way it was decided to treat it and because of the theories concerning its physiopathology. A pelvic mass that appeared 5 years after hysterectomy with bilateral salpingo-oophorectomy for a fibroid proved to be an ovarian cancer. The diagnosis was difficult and the treatment very complicated. PMID- 4040541 TI - [Changes in % free testosterone and sex-hormone binding globulin during danazol administration]. AB - To clarify the androgen balance on the administration of danazol a study was conducted on the levels of % free testosterone (% free T) and sex-hormone-binding globulin (SHBG) during the therapy and the binding properties of danazol to SHBG and androgen receptor. It was found that danazol displaced testosterone (T) from SHBG and R1881 from androgen receptor, in vitro. During treatment with danazol, levels of % free T were increased about three fold, but in contrast the SHBG concentration were significantly decreased. Similar changes in % free T were observed by computer simulation. These data suggest that the androgenic effects of danazol were the results of increased free T levels by the T-displacing ability of danazol from SHBG. The concentration of SHBG might be reduced as a consequence of increased levels of free T. On the other hand, danazol binding to androgen receptor might partially inhibit the action of excess amounts of free T, because the androgenization during therapy was too weak to compare the levels of free T. PMID- 4040542 TI - [Cisplatin and ovarian carcinoma--early detection of cisplatin-induced nephrotoxicity]. AB - Cis-dichlorodiammine platinum (CDDP) has recently been introduced for the treatment of human malignancies. CDDP belongs to the group of heavy metals and has nephrotoxicity, whose side effects limit the dose that can be used in patients. The urinary excretion of lactate dehydrogenase (LDH), gamma-glutamyl transpeptidase (gamma-GTP), alkaline phosphatase (ALP), arylamidase (AA) activity and beta 2-microglobulin was determined in ovarian cancer patients receiving sequential combination chemotherapy with CDDP, adriamycin (ADM) and cyclophosphamide (CPA) (PAC chemotherapy) to evaluate the sensitivity of these indices for acute renal tubular damage and compared with the change in serum BUN, Cr and Ccr values. Increases in enzyme excretion after PAC chemotherapy were more often noticed and the urinary enzyme activity varied up to the 10.4-fold of the control, while serum BUN, Cr and Ccr values remained almost within normal limits. Enzyme excretion returned almost to the normal value in one week. A comparison between the urinary enzyme excretion especially AA value and serum BUN, Cr and Ccr values indicated that the serial determination of the urinary AA excretion pattern is more useful in detecting CDDP-induced nephrotoxicity than that of serum BUN, Cr and Ccr values. PMID- 4040543 TI - The antiestrogenic effect of clomiphene on perineal tumescence of the baboon in an in vitro fertilization program. AB - In a nonhuman primate in vitro fertilization program clomiphene citrate was used to superovulate the chacma baboon Papio ursinus. The antiestrogenic effect of clomiphene citrate was demonstrated locally on the perineal tumescence. In comparing the result of 50 spontaneous cycles and 18 clomiphene citrate stimulated cycles, there was a statistical significant influence on cycle length and duration and degree of perineal swelling. This inhibitory effect on perineal tumescence of the baboon is another example of a local antiestrogenic effect of this drug. Furthermore, it nullified an important clinical parameter of ensuing ovulation. PMID- 4040544 TI - One year of ethanol feeding increases circulating thyroid hormones in the dog. AB - Nine greyhound dogs were fed ethanol for 1 year to examine the effects of long term ethanol feeding on circulating thyroid hormones. The dose of ethanol consumed per day was 2 gm/kg for the first month, 3 gm/kg for the second month, and 4 gm/kg for the rest of the study. Plasma triiodothyronine (T3), thyroxine (T4), and reverse triiodothyronine (rT3) were measured by radioimmunoassay. Plasma T3 and T4 concentrations increased significantly during the period of ethanol administration compared with control values (ANOVA, P less than 0.005). Levels of rT3 showed a trend to increase, although this was not significant. Resin T3 uptake decreased significantly (ANOVA, P less than 0.005) and the calculated free T4 index and free T3 index showed significant elevations (ANOVA, P less than 0.005) during ethanol administration. The results of this study indicate that long-term ethanol feeding to dogs induces an increase in circulating thyroid hormones. PMID- 4040545 TI - Adenoid histamine and its possible relationship to secretory otitis media. AB - We have shown that adenoid tissue contains large amounts of the inflammatory mediator histamine. Children with fluid present in both ears at operation were found to have increased amounts of histamine in their adenoid tissue compared to a group with no signs or symptoms of SOM. Also mouth breathing and nasal obstruction were associated with adenoid histamine content whereas other signs and symptoms were not. No significant differences in adenoid weight were seen between SOM and non SOM patients. Histamine, both free and cell-associated, was found in nasopharyngeal secretions and middle-ear fluid although the source and mechanism of release has not yet been identified. We suggest that the benefits of adenoidectomy in children with SOM may possibly come from removing a potential source of inflammatory mediators in the vicinity of the Eustachian tube. PMID- 4040546 TI - Multiple molecular forms of prolactin during pregnancy in women. AB - The distribution of isomorphic forms of prolactin in the serum of pregnant women was studied by gel filtration chromatography. Using this technique we were able to resolve three peaks, detected by radioimmunoassay: they were termed 'big-big', 'big' and 'little' prolactin in order of decreasing size, with approximate molecular weights greater than 100 000, 50 000 and 21 000 respectively. They displayed a comparable immunoreactivity to the antiserum employed in the radioimmunoassay, as determined in competition experiments. The relative amount of each hormone form in serum changed during the third trimester of pregnancy. At week 33 of pregnancy, 'little' prolactin accounted for 63.2 +/- 7.7% of the total circulating hormone present in the serum of five normal pregnant women. During the progression of pregnancy, there was a gradual increase in the low molecular weight prolactin, so that, at the time of delivery, the larger forms of the hormone were present only in small amounts. PMID- 4040547 TI - Role of the uterine cervix in inhibition of sexual behaviour in lactating rats. AB - Treatment of ovariectomized rats with progesterone-filled constant-release implants, which increased serum progesterone concentrations to 99.4 +/- 5.0 nmol/l, facilitated the induction of lordosis behaviour by subsequent treatment with oestradiol benzoate (OB, 10 micrograms). Concurrent treatment with the dopamine receptor antagonist domperidone (two daily injections of 2.5 mg/rat), which increased serum prolactin concentrations, did not inhibit the behavioural response of ovariectomized progesterone-treated rats to OB. If the treatment was combined with stimulation of the uterine cervix it inhibited lordosis to a level which was comparable with that of progesterone-domperidone-treated rats, which had been ovariectomized and from which the pups had been removed on the day of parturition. The cervical stimulation did not increase the amount of prolactin secreted by the pituitary gland in response to an injection of domperidone. The behavioural effect of cervical stimulation was blocked by injecting an anaesthetic paste (0.1 ml lidocain-prilocain) intravaginally against the cervix. The effect of cervical stimulation, or of parturition, lasted only for a few days and sexual behaviour was inhibited during a prolonged period of lactation. Sucking by the pups on the nipples of the mother may be required for preventing sexual behaviour during the entire period of lactation. PMID- 4040548 TI - Thyrotrophin stimulation of mitogenesis of the rat thyroid cell strain FRTL-5: a metaphase index assay for the detection of thyroid growth stimulators. AB - Thyroid-stimulating hormone (TSH) has been shown to stimulate mitosis in cultures of the continuous thyroid cell strain FRTL-5, and this system may be used to quantify the growth-promoting effects of thyroid stimulators. Removal of TSH from the culture medium led to a progressive decline in the metaphase index (MI) to zero, after 7 days. Thus the cell culture conditions may be manipulated so that metaphases are absent in control cultures, i.e. in the absence of TSH. Restimulation with TSH caused an increase in mitosis only after a lag-phase of 20 24 h. A maximum MI was observed between 40 and 50 h, with a secondary peak between 70 and 75 h. An immunoglobulin G (IgG) preparation from a thyrotoxic patient with a small goitre which was a potent stimulator of adenylate cyclase in these cells produced a similar time-course. A dose-response relationship to TSH was obtained 47 h after addition of the hormone. Significant stimulation was observed with 10 mu. TSH/l, and maximal stimulation with 1 unit TSH/l; the highest dose tested (10 units TSH/1) slightly decreased the MI below the maximum. Stimulation of these cells appeared to be TSH specific, since FSH, human chorionic gonadotrophin, LH and isoproterenol did not induce mitosis. Epidermal growth factor under the experimental conditions employed was unable to induce mitosis. However, an increase in mitosis was observed with the adenylate cyclase stimulator forskolin. These experiments confirm the mitogenic properties of TSH and we describe a metaphase index assay for the detection of thyroid growth promotors. PMID- 4040549 TI - Intersexuality in five pigs, with particular reference to oestrous cycles, the ovotestis, steroid hormone secretion and potential fertility. AB - Reproductive tissues, steroid hormone secretion, and sexual behaviour have been examined in five gilts, in each of which the right gonad was an ovotestis. Although from different females, these animals were sired by the same boar and each possessed an XX sex chromosome constitution as determined by karyotype analysis of blood cells. Despite variable amounts of testicular tissue in the ovotestis and unilateral development of a prominent epididymis, four of the animals had oestrous cycles of normal duration (20-22 days) and extended periods of standing oestrus (3-6 days). The fifth animal did not have detectable oestrous cycles but was extremely aggressive in the presence of a mature boar. Two of the gilts were mated, and there were small numbers of embryos in each uterine horn 23 and 26 days later. Removal of the ovary did not prompt compensatory hypertrophy in the ovarian portion of the ovotestis, nor did injection of pregnant mare serum gonadotrophin stimulate detectable follicular growth in ovarian tissue adjoining testicular tissue. Concerning the aetiology of this intersex condition, the unilateral appearance of an ovotestis precludes any simple involvement of a translocated portion of the Y chromosome or systemic effects of unusual titres of the putative H-Y antigen. However, bearing in mind a predisposition to gonadal asymmetry in eutherian mammals, a case is advanced for apposition or incorporation of adrenocortical tissue in the right embryonic ovary. The resultant virilization of neighbouring reproductive tissues would stem from adrenocortical androgen synthesis. PMID- 4040550 TI - High-dose versus low-dose cisplatin in advanced head and neck squamous carcinoma: a randomized study. AB - From November 1981 to February 1983, 64 patients with advanced head and neck squamous carcinoma were randomly treated with either high-dose (120 mg/m2) or low dose (60 mg/m2) cisplatin. Of the 62 eligible patients, 59 were evaluable: the response rate observed in patients receiving high-dose and low-dose cisplatin was 16.1% and 17.8%, respectively. Survival was superimposable in the two treatment arms. No evidence of dose dependency of cisplatin activity in advanced head and neck squamous carcinoma was noted in this randomized trial. PMID- 4040551 TI - Curative testis cancer therapy: psychosocial sequelae. AB - We examined the long-term impact of advanced testis cancer and its curative therapies on emotional states and outlook on life, employment, intimate relationships, and sexual function. The sample consisted of 74 nonseminomatous and seminomatous tumor patients who had completed treatment two to ten years ago. The majority of men felt that surviving the debilitating treatment(s) was both an accomplishment and worthwhile trade-off. Neither the rate of unemployment (7%) nor divorce (10%) was remarkable. The most critical outcome was in the area of sexual functioning. One fourth to one half of the men reported some type of sexual impairment. Multiple regression results indicate that ejaculatory dysfunction, a side effect of the retroperitoneal lymph node dissection, is significantly associated with distress about both infertility and sexual impairment. Men with sexual impairment report more psychological symptoms, strained intimate relationships, and negative changes in other areas of life functioning. These data, while not definitive, suggest that there are delayed effects and that the subgroup of men, who are least likely to disclose these problems to physicians, are at greater risk for the deleterious outcomes. PMID- 4040552 TI - A comparison of the antiemetic efficacy of prochlorperazine and metoclopramide for the treatment of cisplatin-induced emesis: a prospective, randomized, double blind study. AB - This study compared high-dose metoclopramide and prochlorperazine for their antiemetic activities in the treatment of patients with solid tumors receiving cisplatin-based cancer chemotherapy, in a prospective, double-blind fashion. Sixty patients were entered in the study, and 28 patients on each regimen were evaluable. For regimen 1, metoclopramide was given intravenously (IV) over 15 minutes at a dose of 2 mg/kg 30 minutes before, 30 minutes after, and three hours after treatment with cisplatin. In regimen 2, prochlorperazine was given IV 30 minutes before and three hours after the cisplatin; a placebo was administered at 30 minutes after cisplatin. There was no statistically significant difference between the two regimens in their antiemetic efficacies during the first three hours. For emesis that occurred from three to 24 hours after administration of cisplatin, prochlorperazine was marginally superior. The median number of emeses in the metoclopramide regimen was 2.5 (range, 0 to 10+) compared to 1.0 (range, 0 to 10+) in the prochlorperazine regimen. This is not a significant difference. The overall incidence of adverse reactions was greater in the metoclopramide regimen, with drowsiness being the most common toxicity for both antiemetic programs. Thus, IV high-dose metoclopramide and prochlorperazine are similar and effective in the management of cisplatin-induced emesis. IV prochlorperazine at 20-mg dosage is surprisingly effective. PMID- 4040554 TI - Cholecystokinin potentiates dopamine-mediated behaviors: evidence for modulation specific to a site of coexistence. AB - Cholecystokinin coexists with dopamine in mesolimbic neurons in mammalian brain. When injected directly into the nucleus accumbens, cholecystokinin (CCK) potentiated dopamine (DA)-induced hyperlocomotion and apomorphine-induced stereotypy. These effects were not mimicked by nonsulfated CCK, but were blocked by proglumide, a putative CCK antagonist, as well as by antisera raised against sulfated CCK. CCK alone had no effect on locomotion or sterotypy, indicating that this peptide acts primarily as a modulator of DA-mediated behaviors in the mesolimbic pathway. In addition, CCK did not potentiate DA-induced hyperlocomotion or apomorphine-induced stereotypy when injected into the caudate nucleus, where CCK and DA are localized in separate neurons in rats. Facilitation of DA-mediated behaviors by CCK may represent a functional interaction specific to the neuromodulator-neurotransmitter coexistence phenomenon. PMID- 4040553 TI - Antiemetic efficacy of high-dose dexamethasone versus placebo in patients receiving cisplatin-based chemotherapy: a randomized double-blind controlled clinical trial. AB - The antiemetic effect of short courses of high-dose dexamethasone was compared with that of placebo in 64 patients receiving cisplatin-based cancer chemotherapy, in a double-blind randomized clinical trial. All patients were receiving cisplatin for the first time. Dexamethasone was given intravenously (IV) at a dose of 20 mg, two hours before and 3, 6, 9, and 12 hours after chemotherapy. Patients were crossed over to dexamethasone on the second cycle of chemotherapy if they experienced unacceptable gastrointestinal (GI) toxicity after initial treatment with placebo. Nine of 32 patients receiving dexamethasone and seven of 32 patients receiving placebo did not vomit. The median duration of nausea was significantly shorter (one-half hour) for the dexamethasone-treated group compared with that of placebo (31/2 hours). The number of patients who experienced unacceptable GI toxicity was significantly greater (53%) for the placebo patients than for those treated with dexamethasone (25%). Patients crossing over to dexamethasone after initially receiving placebo had a median duration of nausea of 11/2 hours and 24% did not vomit, results comparable to the first treatment group. We conclude that high-dose dexamethasone is only minimally effective as an antiemetic agent in patients receiving cisplatin-based chemotherapy. PMID- 4040555 TI - Gangliosides alter morphology and growth of astrocytes and increase the activity of choline acetyltransferase in cultures of dissociated septal cells. AB - Administration of gangliosides has been reported to stimulate regeneration of motoneurons and of central dopaminergic and cholinergic neurons. To shed light on the mechanism by which gangliosides mediate the effects on cholinergic neurons, we studied their actions on cultures of cells dissociated from the septal area of fetal rat brains. These cultures contain cholinergic neurons, which, in vivo, give rise to the cholinergic septo-hippocampal pathway. Gangliosides produced prominent changes in the morphological appearance of the cultures. In contrast to control cultures, which contained many process-bearing cells and a confluent layer of flat cells, there were no flat cells in cultures grown in the presence of gangliosides (0.2 to 0.8 mg/ml of medium). Using immunocytochemical visualization of the astrocytic marker glial fibrillary acid protein, it was shown that all astrocytes in cultures grown in the presence of gangliosides exhibited the morphology of process-bearing cells, whereas in control cultures astrocytes represented the majority of the flat cells. Furthermore, gangliosides attenuated astrocytic proliferation. The effects of gangliosides apparently were not mediated by cAMP, since they could be differentiated from actions of forskolin, an activator of adenylate cyclase. Astrocytic growth and morphology were affected by ganglioside mixtures of various sources and composition and also by the pure gangliosides GM1 and GD1a, whereas lipid and carbohydrate components of gangliosides were ineffective. In contrast to the prominent effects on astrocytes, gangliosides failed to significantly alter survival or fiber growth of cholinergic neurons.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4040556 TI - Depletion of norepinephrine, but not serotonin, reduces long-term potentiation in the dentate gyrus of rat hippocampal slices. AB - Long-term potentiation (LTP) in the hippocampus is a long-lasting enhancement of synaptic efficacy produced by a brief, high frequency repetitive stimulation of afferents. LTP has generated a great deal of interest as a candidate mechanism in learning and memory. A recent in vivo study has shown that depletion of norepinephrine (NE) or serotonin (5-hydroxytryptamine, 5-HT) reduced LTP in the dentate gyrus produced by stimulation of the perforant path. However, it was impossible to tell whether this resulted from depletion in the hippocampus, itself, or was secondary to depletion of other brain areas, and no comparison between hippocampal cell fields was done. Therefore, we have examined the effects of depletion of NE or 5-HT on LTP in the dentate and field CA1 of the isolated in vitro hippocampal slice preparation. We report here that NE depletion markedly reduces the occurrence and amplitude of LTP in the dentate, but not in field CA1. In contrast, depletion of 5-HT does not prevent occurrence of LTP in either area. Furthermore, pharmacologic data indicate that beta-receptor stimulation of adenylate cyclase is probably the mechanism of NE's action in the production of LTP in the dentate. These results suggest that endogenous hippocampal NE is more important to LTP in the dentate than is endogenous 5-HT. PMID- 4040557 TI - Effects of different soybean meals on the incidence of tibial dyschondroplasia in the chicken. AB - Interexperimental variation in the incidence of tibial dyschondroplasia of chickens that occurred in studies on the effect of dietary calcium, phosphorus and cholecalciferol metabolites was apparent from previous reports from this laboratory. Since the source of commercial soybean meal used in the diets was known to change, studies were conducted to evaluate different sources of soybean meal on the incidence of tibial dyschondroplasia. A series of experiments demonstrated that the soybean meals from one source consistently produced a high incidence of tibial dyschondroplasia (34-69%); whereas soybean meals from a different source consistently produced low incidences (14-28%). This same relationship was found with soybean meals from these two plants produced a year apart. When the levels of two soybean meals that produced a high incidence of tibial dyschondroplasia were reduced in the diet from 35 to 24 12% the incidence of tibial dyschondroplasia was reduced from 60 and 69% to 25 and 20% to 15 and 10%, respectively. The most striking difference between the meals observed by chemical analysis was in the high antitrypsin and urease values of the meals that induced tibial dyschondroplasia. Chickens fed the soybean meal that reduced tibial dyschondroplasia also had reduced pancreas size in one experiment but not another. The soybean meals that induced tibial dyschondroplasia caused an increase in testes size but had no effect on liver, adrenal and thyroid size or plasma levels of calcium, phosphorus and triiodothyronine (T3). No difference in the utilization of the diets as measured by metabolizable energy values and lipid calcium, phosphorus or phytin phosphorus retention was found between the soybean meals that induced high or low incidence of tibial dyschondroplasia with chickens at 19-21 d of age. PMID- 4040558 TI - Effects of beef, soy and conventional diets on body composition and plasma lipids of young pigs fed restricted or liberal amounts of diet. AB - Effects were determined of restricted and liberal feeding of beef-based, soy based and conventional diets on growth rate, nutrient absorption, body composition and plasma lipid and urea concentrations of young pigs. Beef and soy diets contained more fat (40-50% of calories vs. 8-9%) and cholesterol (0.09 vs. 0%) than did conventional diets; calorie and protein intakes were equal across diets. Beef-fed pigs had greater average daily gain and absorption of fat and gross energy than did conventionally fed pigs; soy-fed pigs had intermediate growth rates but the greatest absorption of fat and gross energy. With restricted intakes, percentage of body fat was greater in soy-fed pigs than in pigs fed a conventional diet or beef and with liberal feeding, greater in soy- and beef-fed pigs than in pigs provided with a conventional diet. Plasma free fatty acid, triglyceride and cholesterol concentrations were greater in soy- and beef-fed pigs than in conventionally fed pigs. These results indicate that absorption and subsequent partitioning of nutrients toward body fat are influenced by composition as well as the amount of diet consumed. Our results also demonstrate that the pig can successfully be fed diets resembling human diets (i.e., high fat) and because of its physiological similarities to humans our understanding of nutrition and lipid metabolism of humans may be advanced. PMID- 4040559 TI - Catabolism of newly formed triglyceride-rich lipoproteins and serum high density lipoproteins in rats fed soybean phospholipid and soybean oil. AB - Previous research has shown that serum cholesterol and apolipoprotein (apo) A-I were lower and serum apoB was higher in rats fed soybean phospholipid (PL) than in rats fed soybean oil. Secretion of cholesterol and apoA-I, but not apoB, from the liver and intestine was lower in rats fed soybean PL. In the present study catabolism of newly formed triglyceride (TG)-rich lipoproteins, from the liver and intestine, and of serum high density lipoproteins (HDL) were compared in rats fed soybean PL and in rats fed soybean oil. The following results were seen: Feeding of soybean PL was related to more TG and less cholesterol in intestinal lymph chylomicrons (CM) and hepatic very low density lipoproteins (VLDL) than was feeding of soybean oil. A lesser amount of the TG, labeled with [3H]oleate in CM and hepatic VLDL, was incorporated into the adipose tissue and muscle in vivo. The clearance of CM-TG from plasma was higher, but that of VLDL-TG and apoB labeled with [3H]lysine was lower. The catabolism of 125I-labeled HDL from the plasma was lower while hepatic uptake of 125I-labeled HDL, in vivo and in vitro, was higher. These results indicate that soybean PL modifies the catabolism of the respective serum lipoproteins. Therefore, we suggest that changes in both the catabolism and secretion of lipoproteins are responsible for the altered serum lipid and apolipoprotein patterns found in rats fed soybean PL. PMID- 4040560 TI - Targeting of coenzyme Q10 solubilized with soy lecithin to heart of guinea pigs. PMID- 4040561 TI - Utilization of soy protein isolate mixed with rice protein in Japanese women. AB - Utilization and requirement of soy protein isolate (SPI) and SPI-rice combination were examined in twenty-five female students. After 1 day on protein-free diet, each subject received a low-protein diet for 10 days. The protein sources were SPI for ten subjects and SPI-rice combination, in which the ratio of two proteins was 6:4, for fifteen subjects. The nitrogen intakes were about 45, 65 and 85 mg/kg in both the two series of experiments. Energy intake was at an approximate maintenance level of 36.1 +/- 3.0 kcal/kg. Apparent nitrogen balance improved with increase in nitrogen intake. The regression equations between nitrogen intake (X, mg/kg) and balance (Y, mg/kg) are shown in the following: SPI: Y = 0.411 X - 40.8 (n = 10, r = 0.812) SPI and rice protein: Y = 0.392 X -32.7 (n = 15, r = 0.739) From the above equations, the maintenance intakes of SPI and SPI rice combination for an apparent nitrogen equilibrium were calculated to be 99 and 83 mg N/kg, respectively. Digestibilities were 98.2 +/- 5.0% for SPI and 93.1 +/- 6.1% for SPI-rice combination. The NPUs of SPI at intake levels of 40, 60 and 80 mg N/kg were 47 +/- 24 (n = 4), 49 (n = 2) and 44 +/- 3 (n = 4), respectively. The NPUs of SPI and rice mixed protein at intake levels of 45, 70 and 90 mg N/kg were 67 +/- 13 (n = 5), 51 +/- 7 (n = 5) and 54 +/- 12 (n = 5), respectively. It was concluded from the present study that both SPI and the SPI-rice combination had a high nutritive efficiency comparable with that of egg protein. PMID- 4040562 TI - Pharmacosexology update: yohimbine and sexual function. PMID- 4040563 TI - Adolescent alcoholism. PMID- 4040564 TI - Neonatal pulmonary hypoplasia with premature rupture of fetal membranes and oligohydramnios. AB - We assessed pulmonary function and compression deformities in 76 preterm infants less than or equal to 34 weeks gestation who had premature rupture of membranes (PROM) for longer than 5 days (mean +/- SD 18.8 +/- 15.4 days, range 6 to 90 days). Twenty-one of the 76 infants had oligohydramnios and positional deformities at birth; however, only two infants met all the criteria for the oligohydramnios tetrad. All 21 required assisted ventilation from the moment of birth. Twenty infants had clinical evidence of pulmonary hypoplasia; 18 of these died. Pulmonary hypoplasia was confirmed by significantly low wet lung weights, low lung DNA content, or low radial alveolar counts in the 13 infants with postmortem examinations. Fifty-five infants with PROM for longer than 5 days did not have positional deformities. Twenty-one required assisted ventilation, of whom 10 had severe oligohydramnios. Eleven of the 21 died; autopsies were performed. All had normal wet lung weights, but seven had significantly decreased radial alveolar counts, implying a less severe but still fatal form of pulmonary hypoplasia. None of the remaining 34 infants had lung disease, and only three had oligohydramnios. We conclude that pulmonary hypoplasia can result from PROM associated with severe oligohydramnios of as short as 6 days duration. Furthermore, fatal pulmonary hypoplasia can occur with little or no external deformation. PMID- 4040565 TI - Physical growth and developmental outcome in very low birth weight premature infants at 3 years of age. PMID- 4040566 TI - Precocious increase of sucrase activity by carbohydrates in the small intestine of suckling rats. I. Significance of the stress effect of sugar-induced diarrhea. AB - In this paper, we analyze the factors involved in the precocious increase of sucrase activity evoked by the early feeding of sucrose in suckling rats, and particularly, the role of diarrhea and stress in this phenomenon. Ten-day-old rats were removed from their mothers and gavage fed for 4 days at 3-h intervals either a basic low carbohydrate milk formula (10.8% fat, 8% protein, 1.4% carbohydrate; all by weight/volume) or basic low carbohydrate milk with: lactose (13%), fructose (13%), or Polycose (2%, 6%, or 13%); all formulas were isocaloric. Feeding the formula containing fructose or high (13%) Polycose led to diarrhea and evoked a concurrent increase of small intestinal sucrase activity. In further experiments, 11-day-old rats were fed the basic formula, the lactose (13%), the fructose (13%), and a sucrose (13%) formula for 8 h between 2 a.m. and 10 a.m. Also, 10-day-old rats were fed 0.5 ml of a solution of 5% mannitol in water while nursing with their mothers. The serum corticosterone levels were substantially increased within 8 h after the initiation of feedings with sucrose and fructose milks and the mannitol solution. The mannitol-fed rats also developed diarrhea within a day in association with a marked increase in sucrase activity. We conclude that a precocious increase of sucrase activity in the small intestine of suckling rats by dietary sugars is not caused by substrate induction, but is mainly due to the effect of stress. The stress is caused by diarrhea which is evoked by the feeding of indigestible and/or unabsorbable amounts of sugar. PMID- 4040567 TI - Physiological model for the pharmacokinetics of cis-dichlorodiammineplatinum (II) (DDP) in the tumored rat. AB - A physiological model has been developed to describe the disposition of cis dichlorodiammine-platinum(II) (DDP) following i.v. dosing in the female rat bearing the Walker 256 carcinoma. The model simulates concentrations of DDP and its mobile and fixed metabolites in plasma, liver, gut, skin, muscle, tumor, carcass, and kidney, and DDP and mobile metabolite excretion following a 4 mg/kg dose. In the kinetic model, DDP binds irreversibly to low MW nucleophiles and macromolecules (largely proteins) within the plasma and tissue compartments to form mobile and fixed metabolites, respectively. Reaction rates for the formation of each metabolite are tissue/organ specific. The rate constant for the biotransformation of DDP to fixed metabolite in plasma (k2P = 0.0082 min-1) was determined from in vitro incubation studies. This rate was used as the basis for estimating the biotransformation rate constants for DDP to fixed and mobile metabolites in other compartments. Both DDP and mobile metabolite are assumed to follow flow-limited transport, to freely traverse compartmental barriers, and to partition equally in all compartments. Both are excreted in the urine, the major route of Pt elimination. Urinary excretion is modeled as a linear process involving filtration only; an assumption based on a calculated renal clearance of 1.1 ml/min, a value very similar to the estimated GFR. Biliary excretion is a minor route of mobile metabolite elimination and is modeled as a linear process occurring in the liver. Four hours after dosing, approximately 60% of the administered Pt remains in the tissues and plasma. Of this, over 75% of the plasma Pt and 90% of the metal ion in every other compartment is fixed (protein bound). Fixed Pt can be eliminated from a compartment only after its biotransformation to mobile metabolite. In most compartments this rate of elimination corresponds closely to the average rate of protein turnover in that compartment. PMID- 4040568 TI - Cis- and trans-4-n-Propyl-1,2,3,4,4a,5,6,10b-octahydrobenzo(f)quinolines. AB - Cis- and trans-4-n-Propyloctahydrobenzo(f)quinolines 4a,b were prepared for further assessment of dopaminergic effects of non-oxygenated dopamine congeners. The trans isomer 4b exhibited marked dopamine-like effects in the cat cardioaccelerator nerve assay and in a rat rotation model. Compound 4b produced dose-related lowering of blood pressure in the cat. The cis isomer 4a was inactive in these assays. Both compounds were inactive in a dopamine binding assay, but both appeared active in a spiroperidol binding assay. Both compounds are active alpha 1- and alpha 2-adrenoceptor antagonists. Compound 4b provides evidence that alpha 2-adrenoceptors and dopamine receptors are different entities, since this compound is an alpha 2 antagonist and a dopamine receptor agonist at presynaptic sites. PMID- 4040569 TI - Continuous intravenous infusion of phencyclidine in unrestrained rats results in the rapid induction of tolerance and physical dependence. AB - The continuous infusion of 45 mg/kg/24 hr of phencyclidine (PCP) into the jugular vein of unrestrained rats induced tolerance to PCP-induced impairment of forced motor activity and physical dependence in 3.5 and 7 days, respectively. In drug naive rats, an i.v. 2-mg/kg PCP test dose abolished rotarod performance for more than 20 min which returned to pretreatment values at 40 min. Eight hours after the termination of 3.5 days of infusion, rotarod performance of PCP-infused rats was significantly less impaired by the PCP test dose at 20 min than that of saline-infused controls. After infusion of PCP for 7 days, the duration of performance abolition produced by the PCP test dose (given 8 hr after the termination of infusion) was shortened further with performance significantly better than that of saline-infused controls at both 10 and 20 min. The results showed a greater than 2-fold tolerance development to this PCP effect and suggest the observed tolerance to be mainly functional in nature. Abrupt withdrawal of PCP after infusion for 7 days resulted in an abstinence syndrome with the following signs: piloerection, increased susceptibility to audiogenic seizures, transient weight loss and reductions in exploratory activity and rotarod performance. The first withdrawal signs were noted 4 hr after the termination of infusion. At 24 hr of abstinence, most of the withdrawal signs had subsided. The reduced rotarod performance, associated with withdrawal, could be reversed by a single i.v. dose of 2 mg/kg of PCP. The reversibility of this sign supports the interpretation of impaired rotarod performance after withdrawal as being an abstinence sign and adds to the experimental evidence that physical dependence on PCP is inducible within 7 days in rats. PMID- 4040570 TI - Pinealectomy delays puberty in ewe lambs. AB - Fifteen pinealectomized and 15 unoperated ewes were exposed to constant light for 3 weeks before and 10 weeks after lambing. Fourteen pinealectomized and 15 unoperated ewes were allowed to lamb outdoors. Five ewe lambs born in constant light to the 2 groups of dams were pinealectomized at 10 weeks of age. Ewes and lambs were then returned to the field. Puberty (determined by weekly progesterone analysis) was significantly delayed (P less than 0.05) in the pinealectomized ewe lambs. Median pubertal age in pineal-intact ewe lambs was 37 weeks compared to 49 weeks in pinealectomized lambs. Constant light during the first 10 weeks of life had no effect upon puberty onset nor did the pineal status of the dam. Control lambs entered seasonal anoestrus at the time pinealectomized ewe lambs were entering puberty. Pinealectomized lambs entered anoestrus at the same time as control lambs were beginning their second breeding season. These results confirm a key role of pineal-mediated hormonal signals in the control of puberty in the sheep. PMID- 4040571 TI - Elevated peripheral concentrations of LH block ovulation and increase thecal and serum progesterone in the hamster. AB - Insertion of osmotic minipumps containing 1 mg ovine LH on Day 1 (oestrus) elevated circulating serum concentrations of LH, progesterone and androstenedione when compared with values at pro-oestrus. Ovulation was blocked for at least 2 days at which time there were twice the normal numbers of preovulatory follicles. Follicular and thecal progesterone production in vitro was elevated when compared with that in pro-oestrous controls. Follicular and thecal androstenedione production in vitro was lower than in controls even though serum concentrations of androstenedione were elevated; the higher androstenedione values may be due to the increase in number of preovulatory follicles when compared with pro-oestrous controls. Follicles from LH-treated hamsters aromatized androstenedione to oestradiol and follicular production of oestradiol was similar to that in pro oestrous follicles despite low follicular androstenedione production in the LH treated group. Treatment with 20 i.u. hCG on Days 4 or 6 after insertion of an LH osmotic minipump on Day 1 induced ovulation of approximately 30 ova, indicating that the blockade of ovulation was not due to atresia of the preovulatory follicles. Serum progesterone concentrations on Days 2, 4 and 6 in LH-treated hamsters were greater than 17 nmol/l, suggesting that the blockade of ovulation might have been due to prevention of the LH surge by high serum progesterone concentrations. PMID- 4040572 TI - Diurnal variations in plasma testosterone concentrations in the male lesser mouse lemur (Microcebus murinus). AB - In 6 isolated adult male lesser mouse lemurs, concentrations of testosterone in plasma were determinated at 6-h intervals over a 24-h period. Blood samples were collected at monthly intervals and for a period of 12 months under natural photoperiod. In this nocturnal prosimian, there were no apparent diurnal changes in testosterone concentrations during the non-breeding season (autumn). During seasonal sexual activity (January-August), diurnal changes in testosterone concentrations were characterized by a significant rise during the light phase. The daily testosterone peak occurred about 8.5 h after sunrise from February to July, but at the beginning (January) or at the end (August) of the breeding season, the daily testosterone peak was displaced to the morning. A circannual testosterone rhythm occurred with the highest testosterone values in May/June and the lowest values 6 months later. The dramatic fall in testosterone concentrations after the summer solstice may be associated with a change in the peripheral metabolism of testosterone. PMID- 4040573 TI - Effect of LH on progesterone and oestradiol production in vivo and in vitro by preovulatory rat follicles. AB - Temporal changes in follicular oestradiol production induced in vitro and in vivo by LH were studied. In-vitro changes were measured by incubating preovulatory rat follicles for 12 h, changing the medium every 2 h. Follicles isolated at various intervals after an injection of 10 i.u. hCG were incubated for 2 h to measure changes in oestradiol production in vivo. In both studies there was an increase in oestradiol production lasting 4 h followed by a sharp decline. Progesterone production was also increased by LH in vitro or hCG in vivo, but remained high. A second exposure to LH did not raise oestradiol synthesis, but increased progesterone synthesis in vitro only. The decline in oestradiol production is most probably due to a decrease in C17-20 lyase activity, because addition of testosterone, but not of 17 alpha-hydroxyprogesterone, increased oestradiol production. Incubation of preovulatory follicles in the absence of LH or incubation of follicles derived from animals in which the spontaneous LH surge was blocked by an injection of pentobarbitone sodium also resulted in a decrease of oestradiol and an increase in progesterone production. This oestrogen progesterone shift was also caused by a decrease in C17-20 lyase activity. The results demonstrate that the changes in steroid production in vivo and in vitro are similar and occur in the presence and absence of LH. It is concluded that the decrease in oestradiol production is dependent on the decrease in the activity of enzymes converting progesterone to aromatizable androgens. PMID- 4040574 TI - Follicular development, ovulation, fertilization and fetal development in tenrecs (Tenrec ecaudatus). AB - Reproduction in female tenrecs was studied on Praslin Island (4 degrees 20'S, 55 degrees 45'E) in the Seychelles from November 1977 to September 1980. Dissection and histological examination of reproductive tracts revealed that each ovary is encapsulated in a bursa. Polyovular follicles were abundant and contained up to 5 oocytes. The occurrence of more implanted fetuses than corpora lutea (CL) indicated successful polyovuly in 25% of pregnancies. No antrum was observed during follicular growth at oestrus, and follicles were relatively small at maturation, reaching a maximum diameter of 570 microns. Ovulation involves a gentle extrusion of the granulosa and ovum into the periovarian space. Spermatozoa were abundant in the female reproductive tract including the periovarian space at oestrus. Spermatozoa penetrated the loosely-packed theca of mature follicles and were present in CL, indicating that intrafollicular fertilization may occur. The relatively small CL formed by eversion, reaching a maximum size after implantation. Fusion of up to four CL occurred in the ovaries of 41% of pregnant females. Polyovulation in the tenrec was confirmed by the occurrence of 10.4 +/- 0.5 (mean +/- s.e.m.) CL and 9.7 +/- 0.5 (mean +/- s.e.m.) implantations. Resorption occurred in 74% of 19 dissectable pregnancies, occurring in both uterine horns in 26% of pregnancies. Coefficients of variation in weights of fetuses in each litter were 10.0-26.8%, with the largest value corresponding to 273% variation in fetus weights. Litter size in the Seychelles tenrecs was smaller than in the same species in Madagascar (17.1 +/- 1.9 implantations) where the tenrec is native. PMID- 4040575 TI - Effects of abdominal vagotomy on serum LH concentrations in female rats. AB - Vagotomy on the morning of pro-oestrus did not prevent the pro-oestrous LH surge and rats became oestrous on the following day. However, vagotomized rats then exhibited a period of acyclicity which lasted for 20.4 +/- 1.3 (s.e.m.) days. Food intake and body weight also declined after vagotomy. During the first week after vagotomy, afternoon LH surges generally did not occur, a pattern which was similar in animals pair fed with vagotomized rats. However, pair-fed rats showed oestrous cycles while vagotomized rats were acyclic. At 7 days after vagotomy, LH surges were induced by oestradiol benzoate and progesterone treatment of ovariectomized rats. Vagotomy suppressed the post-ovariectomy increase in serum LH at 7 and 21 days after surgery. These results, combined with those of other studies, suggest impairment of LH release in vagotomized rats. PMID- 4040576 TI - Effect of cycle stage on immunoglobulin concentrations in reproductive tract secretions of the mare. AB - The effect of cycle stage on immunoglobulin and albumin levels in serum, follicular fluid, oviductal, uterine and vaginal secretions was measured. There was no variation in serum immunoglobulin levels during the oestrous cycle, although IgM levels were elevated in cyclic mares compared to non-cyclic (immature and anoestrous) animals. Similarly, there was no cyclical variation in follicular or oviductal protein concentrations. In the uterus, IgG and IgA levels relative to total protein were higher in oestrogenic than in progestagenic secretions, while the trend in relative IgM concentrations was reversed. Albumin levels were unchanged. In mares sampled repeatedly from the uterus and vagina during a single oestrous cycle, protein levels in secretions were affected by the collection technique. However, there was variation in absolute IgG, IgA, albumin and total protein concentrations, with maxima during dioestrus and minima at oestrus. Protein concentrations were higher in vaginal than in uterine secretions, although IgA relative to total protein was higher in the uterus than the vagina. PMID- 4040577 TI - Geographical variations in use of surgery for glue ear. AB - Study of geographical variations in the rate of surgery for glue ear reveals striking differences both between English health regions and between health districts. There are two-fold differences between regions and up to seven-fold differences between districts. Analysis of these differences at different levels of population aggregation reveals that professional uncertainty about the indications and value of surgery for this condition is the major factor responsible. In addition, the availability of otolaryngologists influences the surgical rate at district though not at regional level. The method used in this study is unable to determine the part played by geographical variation in patient expectation and morbidity rate. In contrast to the lack of consensus among otolaryngologists regarding the use of surgery for glue ear, there appears to be a high degree of agreement as regards tonsillectomy. The latter has coincided with the end of the decline in the tonsillectomy rate in the late 1970s. PMID- 4040579 TI - The effect of prostaglandin E1 on motility of the equine gut. AB - Prostaglandin E1 was infused intravenously (25, 50 and 75 ng/kg/min) in three ponies. Changes in gastrointestinal mechanical and electrical activity were recorded from chronically implanted strain-gauge force transducers and electrodes. Dose-dependent responses were obtained: there were significant decreases in electrical spiking activity in the stomach, left large colon and small colon, with a corresponding decrease of activity in the left dorsal colon mechanogram. The small intestine was also affected, showing a decrease in both contraction rate and amplitude, which was more marked in the proximal jejunum than in the ileum. There was an association between these changes in gastrointestinal activity and the presence of discomfort and diminished gut sounds. PMID- 4040578 TI - Assembly of vimentin in vitro and its implications concerning the structure of intermediate filaments. AB - After dialysis against 10 mM-Tris-acetate (pH 8.5), vimentin that has been purified in the presence of urea is present in the form of tetrameric 2 to 3 nm X 48 nm rods known as protofilaments. These building blocks in turn polymerize into intermediate filaments (10 to 12 nm diameter) when they are dialyzed against a solution of physiological ionic strength and pH. By varying the ionic conditions under which polymerization takes place, we have identified two classes of assembly intermediates whose structures provide clues as to how an intermediate filament may be constructed. The structure of the first class, seen when assembly takes place at 10 to 20 mM-salt at pH 8.5, strongly suggests that one of the initial steps of filament assembly is the association of protofilaments into pairs with a half-unit axial stagger. Increasing the ionic strength of the assembly buffer leads to the emergence of short, full-width intermediate filaments at approximately 50 mM-salt at pH 8.5. In the presence of additional protofilaments, these short filaments elongate to many micrometers when the ionic strength and pH are further adjusted to physiological levels. The electron microscope images of the assembly intermediates suggest that vimentin-containing intermediate filaments are made up of eight protofilaments, assembled such that there is an approximately 22 nm axial stagger between neighboring protofilaments. We propose that this half-unit staggering of protofilaments is a fundamental feature of intermediate filament structure and assembly, and that it could account for the 20 to 22 nm axial repeat seen in all intermediate filaments examined so far. PMID- 4040580 TI - Hemangiosarcoma of the seminal vesicle: case report and literature review. AB - We report the clinical, histological and ultrastructural findings of a primary seminal vesicle sarcoma that was proved to be a hemangiosarcoma, the first such case reported. Metastases to the lungs, pleura and peritoneum were discovered at autopsy. PMID- 4040581 TI - Urethral replacement using ileum with an intussuscepted ileal valve for continence. AB - Numerous techniques for replacing the urethra have been previously described, but attempts to provide continence have rarely been satisfactory. Urethral replacement using ileum with an ileal intussuscepted valve for continence has been successfully performed in ten female dogs. Eight of them were available for a 1 to 6-month followup. This neo-urethra has provided good continence and can be easily catheterized. The clinical usefulness of this technique in the treatment of total urethral loss in humans needs to be further explored. PMID- 4040582 TI - [Intraperitoneal cisplatin in peritoneal carcinomatosis patients]. AB - Cisplatin (100 mg) was given by intraperitoneal infusion to 23 patients with peritoneal carcinomatosis. Eighteen patients had gastric cancer, and five had colorectal cancer. The effects of this therapy were as follows. 1) In gastric cancer patients, the mean survival period was 11.0 months. The cumulative survival rate was superior at the level of statistical significance in comparison with controls. 2) The side effects of this agent given intraperitoneally were mild. In particular, nausea was slightly less than with intravesicular or intraarterial infusion. PMID- 4040583 TI - [Antiplatelet antibody and circulating immune complexes in patients with idiopathic thrombocytopenic purpura]. PMID- 4040584 TI - [Urticaria due to the soybeans]. PMID- 4040585 TI - Antitumor activity of methanol extract from roots of Agrimonia pilosa Ledeb. AB - To evaluate the antitumor activity of Agrimonia pilosa LEDEB., the effects of the methanol extract from roots of the plant (AP-M) on several transplantable rodent tumors were investigated. AP-M significantly prolonged the life span of S180-, Meth-A fibrosarcoma- and MM-2 mammary carcinoma-bearing mice by intraperitoneal (i.p.) pre- or postmedication. AP-M also inhibited the growth of S-180 solid type tumor. On the other hand, the prolongation of life span induced by AP-M on S-180 ascites type tumor-bearing mice was markedly minimized or abolished by the pretreatment of cyclophosphamide. AP-M showed considerably strong cytotoxicity on MM-2 cells in vitro, but the effect was diminished to one-tenth by the addition of serum to the culture. Against the host animals, the peripheral white blood cells in mice were significantly increased from 2 to 5 days after the i.p. injection of AP-M. On 4th day after the injection of AP-M, the peritoneal exudate cells which possessed the cytotoxic activity on MM-2 cells in vitro were also increased to about 5-fold those in the non-treated control. The spleen of the mice was enlarged, and the spleen cells possessed the capacity to uptake 3H thymidine. However, AP-M did not show direct migration activity like other mitogens against spleen cells from non-treated mice. These results indicate that the roots of Agrimonia pilosa contain some antitumor constituents, and possible mechanisms of the antitumor activity may be some host-mediated actions and direct cytotoxicity. PMID- 4040586 TI - [Comparative clinico-instrumental characteristics of different morphological variants of hypertrophic cardiomyopathy]. AB - Six morphologic variants of hypertrophic cardiomyopathy (HCMP) have been identified on the basis of the echocardiographically-documented extent and localization of left-ventricular hypertrophy in 34 patients with HCMP. More than half of the patients had no complaints. The more characteristic echocardiographic features of the disease included a considerable thickening of one or more departments within the left ventricle, the size of its cavity being diminished. In most cases, HCMP was associated with considerably enlarged R waves on the electrocardiograms from 35 precordial leads that were usually combined with ST segment depression and T wave inversion. The latter two features often provided grounds for a hyperdiagnosis of coronary heart disease (CHD). What distinguishes HCMP from CHD is the discrepancy between marked and persistent pathologic electrocardiographic changes and a relatively uneventful clinical picture of the disease. The comparison of echocardiographic and ECG charting data allows a more detailed assessment of the kind of left-ventricular hypertrophy in HCMP patients, and can be used in the differential diagnosis of HCMP vs. CHD. PMID- 4040587 TI - [Laser surgery on the heart conduction pathways]. PMID- 4040588 TI - Congenital malformations and variations in reproductive performance in the ferret: effects of maternal age, color and parity. AB - Demographic data of ferrets from a commercial breeding colony were analyzed for the effects of maternal age, parity and strain on reproductive performance and the frequency of gross congenital abnormalities observed at parturition. Litter size (mean +/- SEM) was found to be greatest for young, primiparous females (10.3 +/- 0.2) and decreased with advancing maternal age and parity to a cohort mean of 8.1 +/- 0.1 for third parity females 16 months of age. Age, parity or strain had no effect on 24-hour neonatal mortality (7%) or mortality from birth to weaning (20%) and an examination of the causes for death suggested that these rates can be reduced. The malformation rate from two cohorts of females whelping at different times of the year was low (less than 1.0%) and not significantly different. A higher frequency of malformed offspring was detected in females of low previous parity (0-2) than in those with three or more. Based on data obtained in this survey, the ferret would seem a valuable alternative, nonrodent species for teratologic investigations using currently recommended protocols. PMID- 4040589 TI - Bone marrow hypoplasia associated with estrus in ferrets. AB - Bone marrow hypoplasia was characterized in a group of female ferrets during prolonged estrus. All ferrets exhibited hematological changes characteristic of various degrees of bone marrow hypoplasia. Hematological findings included initial thrombocytosis and leukocytosis followed by thrombocytopenia, leukopenia and anemia. Platelet counts below 50,000/microliters were observed in 55% of the ferrets. Hemorrhagic anemia due to thrombocytopenia was the most common cause of death and the mortality rate was 40%. Histopathological findings included bone marrow hypoplasia affecting all cell lines and decreased splenic extramedullary hematopoiesis. PMID- 4040590 TI - Use of a new radioactive ligand, 7 alpha, 17 alpha-dimethyl[17 alpha-methyl 3H]19 nortestosterone for the estimation of androgen receptors in rat liver cytosol. AB - The use of the testosterone derivative, 7 alpha, 17 alpha-dimethyl[17 alpha methyl 3H] 19-nortestosterone for the estimation of cytosolic androgen receptors in male rat liver is described. Use of this compound demonstrates binding which has a similar dissociation constant, maximum binding and steroid specificity to that seen with other synthetic testosterone derivatives. In contrast to previous data significant binding to the progesterone receptor also occurs and future studies with this ligand should employ triamcinolone acetonide to block such binding. PMID- 4040591 TI - Choice of anesthetic for intestinal absorption and secretion experiments using rats. AB - The net rates of glucose and water absorption from, and secretion of water into, the lumen of the rat small intestine were compared using alpha-chloralose, halothane, pentobarbitone, and urethane as anesthetics. Water and glucose transport were determined by recirculation of perfusion fluid through the lumen of the jejunum. Net fluid secretion was stimulated by intraarterial (i.a.) infusion of prostaglandin E1 (PGE1) and vasoactive intestinal peptide (VIP). The results show that the anesthetics used exert only minimal influence on the physiological rates of glucose and water absorption and there is no correlation between the small differences in glucose and water absorption among the anesthetics. However, when the fluid secretory mechanism of the mucosa is stimulated with either PGE1 or VIP, pentobarbitone allows the greatest rates of secretion, but halothane prevents secretion. It is suggested that of the anesthetics used, pentobarbitone is the most appropriate for intestinal secretion experiments. PMID- 4040592 TI - Topological approach to embryogenesis. PMID- 4040593 TI - [Evaluation of azthreonam in the treatment of severe infections: study of 17 cases]. PMID- 4040594 TI - Animal models of behavioral pathology and violent aggression. AB - To avoid the danger of an increasing gap between clinical and animal studies and to assure a constant progression of knowledge, psychiatric researchers need to find a common ground of convergence. Such common ground might be found in searching for human and animal models of disturbed behavior, conceptually comprehensive of the variables which may concur in the determination of the behavioral syndromes. PMID- 4040595 TI - Microscopic analysis of the mastoid bone in chronic serous otitis media. AB - The pathologic changes of the middle ear and mastoid bone mucosa in two pediatric patients with long standing chronic serous otitis media were studied by electron and light microscopy. The embryological development of the eustachian tube, middle ear cleft, and mastoid bone suggests a common physiological and anatomical continuity. The histological changes by light and electron microscopy in these patients demonstrates the metaplastic changes of the basal cell of the mucosa differentiating into mucous and keratin cells. These metaplastic changes are associated with the exudative process known as chronic serous otitis media. PMID- 4040597 TI - Unaltered aerobic power and endurance following glucocorticoid-induced muscle atrophy. AB - The present study was undertaken to evaluate whether the muscle atrophy associated with glucocorticoid excess results in a reduction in maximal oxygen uptake (VO2max) and endurance during exercise. Female rats were administered single subcutaneous injections of cortisone acetate (CA) (100 mg X kg-1 b.w.) or the vehicle (1% carboxymethyl cellulose) for 14 consecutive days. The weights of plantaris muscles (which were used as a marker of the atrophy) of CA-treated rats were 27% less than those of plantaris muscles in the vehicle-treated rats. This condition also produced a 12-fold increase in free serum glucocorticoid concentrations (cortisol) but did not alter serum androgen (testosterone) levels. Peak VO2 (ml X kg-1 X min-1) and endurance were greater in CA-treated vs vehicle treated animals; however, these effects were shown to be a function of body weight loss. Homogenate oxygen uptakes in the presence of pyruvate or palmitate were also similar in slow-twitch soleus, fast-twitch red vastus, and fast-twitch white vastus lateralis muscles between CA- and vehicle-treated groups. These data provide no evidence to demonstrate that the catabolic actions of glucocorticoids in skeletal muscle result in a decrement in work capacity through at least 14 d of treatment. PMID- 4040596 TI - Phosphatidylinositol metabolism during fertilization in the sea urchin egg. AB - Fertilization of the sea urchin egg results in a transient decline in the amount of phosphatidylinositol (PI) to a level equal to about 50% of that present in the unfertilized egg. This response begins as early as 15 seconds after insemination. The level of PI reaches a minimum at 30 seconds post-insemination, and returns to the original value between 2 and 5 min later. Pulse labelling studies with 32PO4 and [3H]-inositol showed that the incorporation of these two isotopes into 1-(3 sn-phosphatidyl)-L-myo-inositol 4,5-biphosphate [PtdIns(4,5)P2] increased as much as 50% within one minute after insemination. This suggests that at least part of the reduction in PI levels represents the phosphorylation of PI to form PtdIns(4,5)P2. We also found that the production of [3H]-labelled 1D-myoinositol 1,4,5 triphosphate [Ins(1,4,5)P3] present in the trichloroacetic acid (TCA) soluble fraction of eggs increased over five-fold during the first 10 min post insemination. The temporal correlation between the early burst of PtdIns(4,5)P2 and Ins(1,4,5)P3 formation and the transient increase in intracellular free calcium known to occur in the fertilized egg suggest that the production of PtdIns(4,5)P2 and ultimately Ins(1,4,5)P3 may be associated with calcium mobilization within the egg. PMID- 4040598 TI - MPMLC assists pathologist researching infant defects. PMID- 4040600 TI - Peer review in Minnesota--the Foundation for Health Care Evaluation-1985. PMID- 4040599 TI - [Fetal alcohol syndrome: clinical, metabolic and immunologic follow-up in l4 cases]. PMID- 4040601 TI - A Missouri physician's guide to becoming more PRO-active. PMID- 4040602 TI - Disruption of the three cytoskeletal networks in mammalian cells does not affect transcription, translation, or protein translocation changes induced by heat shock. AB - Mammalian cells show a complex series of transcriptional and translational switching events in response to heat shock treatment which ultimately lead to the production and accumulation of a small number of proteins, the so-called heat shock (or stress) proteins. We investigated the heat shock response in both qualitative and quantitative ways in cells that were pretreated with drugs that specifically disrupt one or more of the three major cytoskeletal networks. (These drugs alone, cytochalasin E and colcemid, do not result in induction of the heat shock response.) Our results indicated that disruption of the actin microfilaments, the vimentin-containing intermediate filaments, or the microtubules in living cells does not hinder the ability of the cell to undergo an apparently normal heat shock response. Even when all three networks were simultaneously disrupted (resulting in a loose, baglike appearance of the cells), the cells still underwent a complete heat shock response as assayed by the appearance of the heat shock proteins. In addition, the major induced 72 kilodalton heat shock protein was efficiently translocated from the cytoplasm into its proper location in the nucleus and nucleolus irrespective of the condition of the three cytoskeletal elements. PMID- 4040603 TI - Coamplification and coexpression of human tissue-type plasminogen activator and murine dihydrofolate reductase sequences in Chinese hamster ovary cells. AB - Expression of human tissue-type plasminogen activator (t-PA) at high levels has been achieved in Chinese hamster ovary (CHO) cells by cotransfection and subsequent coamplification of the transfected sequences. Expression vectors containing the t-PA cDNA gene and dihydrofolate reductase (DHFR) cDNA gene were cotransfected into CHO DHFR-deficient cells. Transformants expressing DHFR were selected by growth in media lacking nucleosides and contained low numbers of t-PA genes and DHFR genes. Stepwise selection of the DHFR+ transformants in increasing concentrations of methotrexate generated cells which had amplified both DHFR genes and t-PA genes over 100-fold. These cell lines expressed elevated levels of enzymatically active t-PA. To optimize both t-PA sequence amplification and t-PA expression, various modifications of the original procedure were used. These included alterations to the DHFR expression vector, optimization of the molar ratio of t-PA to DHFR sequences in the cotransfection, and modification of the methotrexate resistance selection procedure. The structure of the amplified DNA, its chromosomal location, and its stability during growth in the absence of methotrexate are reported. PMID- 4040604 TI - Ethanol-induced late fetal death in mice exposed around the time of fertilization. AB - In the mouse, all autosomal monosomies and trisomies are lethal by the time of birth (Searle, 1981). To test whether ethanol ingested by females shortly after mating induces nondisjunction, as reported by Kaufman (1983) on the basis of cytological evidence, we attempted to determine whether the incidence of intrauterine death was affected by this treatment. The incidence of late death (day 11 postconception or later) was found to be significantly increased when ethanol was administered 2 h following a 30-min mating period, but not when the interval was shorter. Measurements of early death were not sensitive enough (because of the high control frequency) to show an effect of ethanol treatment. Limited cytological data showed an induced incidence of trisomy in line with the excess frequency of late death, but the trisomy incidence by itself was not significantly different from control. The overall level of effect in the present experiment was lower than that reported by Kaufman. PMID- 4040605 TI - Influence of treatment temperature on the genotoxic effects of cisplatin in CHO cells: cytotoxicity, mutagenicity and induction of lesions in DNA. AB - In cells exposed in vitro to the cytotoxic and mutagenic antitumor drug cisplatin (cis-Pt(NH3)2Cl2), various adducts with nuclear DNA are formed. A comparative study was made of the influence of temperature variation during treatment of cultured Chinese hamster ovary (CHO) cells with cisplatin on cytotoxicity, mutation induction and Pt-DNA adduct formation. Before and after treatment (1 h at 32, 37 or 40 degrees C) cells were kept at 37 degrees C. Cytotoxicity increased with temperature; D0 values were 29.6 +/- 1.6, 21.1 +/- 1.2 and 11.4 +/ 0.6 microM at 32, 37 and 40 degrees C, respectively. Pt-DNA binding to DNA at 40 degrees C was 2.0 (+/- 0.3) times as high as at 32 degrees C. This factor remained practically constant over a 24-h post-treatment incubation of the cells, during which about 60% of DNA-bound Pt were removed. As the increase in cytotoxicity between 32 and 40 degrees C was roughly in proportion to that in Pt binding, no substantial changes in the spectrum of adducts appeared to occur. The induction of DNA interstrand cross-links, studied at 32 and 40 degrees C, varied linearly with dose. Influence of temperature on cross-link formation was comparable to that on total Pt binding. Amounts of cross-links highly increased during 24 h after treatment. Plots of cross-links against survival after treatments at 32 and 40 degrees C almost coincided. Induction of 6-thioguanine resistant (HGPRT) mutants at various cisplatin concentrations did not show a clear temperature dependency. Consequently, equitoxic treatments were significantly more mutagenic at 32 degrees C than at 40 degrees C, the opposite of what has been reported for E. coli. PMID- 4040606 TI - Toxicity and mutagenicity of 6 anti-cancer drugs in Chinese hamster V79 cells co cultured with rat hepatocytes. AB - Toxicity and induction of 6-thioguanine-resistant mutants in Chinese hamster V79 cells, co-cultured with or without isolated rate hepatocytes, by 6 anti-cancer drugs (cyclophosphamide, adriamycin, methotrexate, cytosine arabinoside, 6 mercaptopurine and vincristine) were studied. The effect of hepatocyte density on the cloning efficiency and recovery of mutants was found using dimethylnitrosamine as a positive control. In the absence of hepatocytes, this compound was neither toxic nor mutagenic to V79 cells, but in their presence it was highly mutagenic and extremely toxic. The cloning efficiency and mutation frequency of control (untreated) cells was unaffected by hepatocyte density. All the drugs were toxic to V79 cells, although different responses were found for certain of them depending upon whether hepatocytes were present or not. Cyclophosphamide and adriamycin were clearly mutagenic, and 6-mercaptopurine only weakly so. A slight mutagenic effect was seen for cytosine arabinoside, but both methotrexate and vincristine were negative. Here also, the presence or absence of hepatocytes was important. PMID- 4040608 TI - Testing of 3 chemical compounds for aneuploidy induction in the female mouse. AB - The 3 chemicals, 6 mercaptopurine (6-MCP), phenylalanine and para fluorophenylalanine (pFPA) have been tested on mouse oocytes of the Swiss strain for possible aneuploidy-inducing effects. Tests were made at the dictyate stage in young and aged females and at the preovulatory (diakinesis/MI) stage in aged females only. Metaphase II chromosome complements were analysed for aneuploidy resulting from segregational errors arising at the first meiotic division. No evidence of non-disjunction was found either in treated or control groups up to the age of 40 weeks tested. The need to select for gametogenic stage and strain when using a mouse model system for aneuploidy testing, is considered. PMID- 4040607 TI - Heritable translocation study in male mice with trimethyl phosphate. AB - Dominant lethal and heritable translocation studies were performed in male mice receiving a single intraperitoneal injection of trimethyl phosphate (TMP). The germ cell stage investigated was the spermatid. Methyl methanesulfonate (MMS) was used as a positive control in the latter study. A dominant lethal assay gave marked dose-dependent increases in early fetal deaths. Heritable translocations were detected at 1000 or 1500 mg of TMP/kg in F1 male progeny when screening for semi-sterility and cytogenetically analyzing the meiotic or mitotic chromosomes. Translocation induction was higher at the higher TMP dose (14.3%) than at the lower dose (5.3%) and the yield from the higher dose was similar to that induced by 50 mg of MMS/kg (11.0%). Most of the translocation carriers were semi-sterile or sterile. The data confirm conclusions from other dominant lethal studies showing TMP to be capable of causing chromosomal damage in mouse spermatids and show that certain types of damage result in heritable translocations. PMID- 4040609 TI - Neuronal filaments in Alzheimer's, Pick's, and Parkinson's diseases. PMID- 4040610 TI - Thermodynamic compatibility of proteins in aqueous media. Part 2. The effect of some physicochemical factors on thermodynamic compatibility of casein and soybean globulin fraction. AB - A study has been made on the effect of temperature, sodium chloride, pH and cysteine on the thermodynamic compatibility of casein and soybean globulin fraction in aqueous medium. The section of miscibility gap characterizing the influence of the indicated factors on the compatibility of proteins has been determined. Assessment has been made of the influence of pH and cysteine on a) the effective molecular weights of casein and soybean globulin fraction and b) the difference in the intensity of interaction between each protein and a solvent. The experimental data obtained on the compatibility of proteins were found in good agreement with the theoretical concepts which establish the dependence of the compatibility of polymers on the ratio of their molecular weights, the intensity of interactions between polymers, as well as on the difference in the intensities of interaction between each of them and a solvent, i.e. on the difference of protein hydrophilicities. PMID- 4040611 TI - Active gamma-carboxylated human factor IX expressed using recombinant DNA techniques. AB - Factor IX (Christmas factor), a vitamin K-dependent plasma protein made in the liver, functions in the middle phase of the intrinsic pathway of blood coagulation. A functional deficiency of factor IX underlies haemophilia B, a chromosome X-linked recessive disease for which the major therapeutic approach is replacement treatment using factor IX concentrates. The cloning and characterization of the gene for human factor IX would mean that human factor IX could be produced in greater yield and purity through using recombinant DNA techniques. We have now used a human factor IX cDNA clone, inserted into a vaccinia virus-derived vector, to infect human hepatoma cells which normally produce no factor IX, and mouse fibroblasts. Fully active factor IX was produced by the hepatoma cells, whereas the fibroblasts produced a protein less active than natural factor IX, even in the presence of high levels of vitamin K. Human factor IX is extensively post-translationally modified, and thus represents probably the most complex protein produced in active form by recombinant DNA techniques to date. Our study also illustrates the potential of vaccinia virus based vectors for expressing significant amounts of complex, clinically useful proteins in eukaryotic cells, in addition to its already demonstrated usefulness for producing live recombinant vaccines. PMID- 4040612 TI - Intrauterine twin demise and oligomeganephronia. AB - Oligomeganephronia, characterized clinically be early renal failure and histologically by large, sparse glomeruli, is of undetermined etiology. This is the first documented report of an intrauterine fetal demise of one twin in association with oligomeganephronia in the other, and suggests that these two conditions may be related etiologically. The suggested mechanism is a renal vascular insult, late in the pregnancy, as the precipitating event. PMID- 4040613 TI - Effect of locus ceruleus lesion on luteinizing hormone secretion under different experimental conditions. AB - The objective of the present study was to determine the participation of the locus ceruleus (LC) in the regulation of the estrous cycle and of luteinizing hormone (LH) release on the afternoon of proestrus and in ovariectomized rats. Lesions of the LC on the morning of proestrus blocked the preovulatory surge of LH in the afternoon of the same day. The estrous cycle became irregular and erratic after LC lesions and displayed a prolonged period of diestrus and estrus which persisted during the entire experimental period (50 days). After this period the level of LH in the afternoon of proestrus was lower in plasma and higher in the adenohypophysis. A decrease in ovarian, uterine, and adenohypophyseal weight was also observed. LC lesions in 7-day castrated rats induced a decrease in plasma LH levels 48 und 72 h later. When these lesions were made before bilateral ovariectomy, they delayed the normal increase in plasma LH levels. From the data obtained we can conclude that lesion of the LC interferes with the cyclic as well as tonic liberation of LH. A functional rearrangement of the central noradrenergic system may occur a long time after the lesion. These effects may be mediated by connections of the LC with: (1) areas whose neurons produce gonadotropin-releasing hormone; (2) areas which in some form are involved in the liberation of gonadotropins, and (3) the median eminence. PMID- 4040614 TI - Cataleptogenic and anticataleptic activity produced by cholecystokinin octapeptides in mice. AB - The catalepsy induced by subcutaneously (sc.) and intracerebroventricularly (icv.) administered cholecystokinin octapeptide sulfate ester (CCK-8-SE) and desulfated cholecystokinin octapeptide (CCK-8-NS), and the effects of CCK-8-SE and CCK-8-NS on haloperidol-induced catalepsy, were investigated in mice. The results demonstrate the bimodal effect of CCK octapeptides in a catalepsy test. With sc. administration CCK-8-SE in the doses of 0.4 or 0.8 mumole/kg, but not CCK-8-NS at any dose, induced catalepsy. Furthermore, the catalepsy induced by CCK-8-SE was of short duration. With icv. administration only 40 pmole CCK-8-NS induced significant catalepsy. When 0.2, 0.4 and 0.8 mumole/kg sc. doses of CCK-8 NS or 0.4 pmole icv. dose of CCK-8-SE or CCK-8-NS was given in combination with intraperitoneal (ip.) administration of 1.0 mg/kg haloperidol, the total duration of catalepsy was suppressed. Finally, CCK-8-SE sc. when given in combination with haloperidol ip., exerted a biphasic, synergistic-antagonistic effect on the haloperidol-induced catalepsy. PMID- 4040615 TI - Viral antibodies in twins with multiple sclerosis. AB - Viral antibodies to measles, rubella, corona, vaccinia, and mumps viruses in serum and CSF (and to Epstein-Barr virus in serum only) were studied in 24 twin pairs, both discordant and concordant for clinical MS. In pairs, CSF antibody titers for rubella in MS monozygotic and dizygotic twins and for vaccinia in dizygotic twins were higher than for unaffected twins. Increased CSF titers among MS twins existed for measles, rubella, and vaccinia when pairing was ignored. Among MS twins, serum rubella and measles and CSF measles antibody titers, and CSF:serum ratios for measles virus, were higher in those who were DW2 positive. PMID- 4040616 TI - Relative postmortem stability of spinal motoneuronal proteins detectable by two dimensional electrophoresis. AB - The suitability of using spinal tissue several hours after death for analysis by high resolution two-dimensional electrophoresis has been examined. It was found that many of the proteins of bovine spinal motoneurons detectable on two dimensional polyacrylamide gels appear to be relatively stable in situ at room temperature during the first postmortem day. When extracts of total proteins from ventral roots and motoneuronal cell bodies isolated from 1-d-old tissue were examined, all spots could be matched to control gels. Upon visual inspection of the gels, postmortem changes in the amount of stain associated with a spot were obvious in three of 364 proteins from isolated motoneuronal cell bodies and none of 237 proteins from ventral roots. Other proteins underwent quantitative changes that were detected only after computer-assisted densitometry on the gels, whereas some did not appear to change at all. In the neuropil surrounding the motoneuron cell bodies, more pronounced changes in protein patterns occurred during the postmortem period. We conclude that properly controlled two-dimensional electrophoretic analyses of postmortem spinal tissue can provide reliable qualitative and quantitative information about the antemortem protein composition of spinal motoneurons. PMID- 4040617 TI - Hypertrophic cardiomyopathy and pregnancy: report of a maternal mortality and review of literature. AB - The first case of maternal mortality with hypertrophic obstructive cardiomyopathy is reported. An additional successfully managed case of hypertrophic obstructive cardiomyopathy and pregnancy is reported. Systemic arterial embolization, which has not been previously reported in hypertrophic obstructive cardiomyopathy with pregnancy is discussed. English language literature on hypertrophic obstructive cardiomyopathy and pregnancy is reviewed, and a management plan has been outlined. PMID- 4040618 TI - Modified Burch versus Pereyra retropubic urethropexy for stress urinary incontinence. AB - Sixty-four women underwent either the modified Burch retropubic urethropexy or the modified Pereyra procedure for surgical correction of stress urinary incontinence. All were evaluated clinically and urodynamically before and one year after surgery. The Burch procedure proved to be superior to the Pereyra procedure in terms of improving pressure transmission to the proximal two-thirds of the urethra (P less than .001), correcting the anatomic defect (P less than .001), avoiding postoperative voiding difficulties (20 versus 30%), and presenting an objective cure rate of 98 versus 85%. The age, parity, and degree of mobility of the urethra and urethrovesical junction did not influence the ability of the Burch and Pereyra procedures to produce efficient postoperative pressure transmission capacity ratio. Both types of surgical procedures were closely comparable in terms of curing stress urinary incontinence, operative time and blood loss, and total hospital stay. PMID- 4040619 TI - Thrombotic thrombocytopenic purpura in early pregnancy. AB - Thrombotic thrombocytopenic purpura during pregnancy in which both mother and fetus have survived has been an exceedingly rare occurrence, due at least in part to the difficulty in distinguishing this uncommon disease from hematologic complications of preeclampsia. In the nonpregnant patient, the use of plasma infusion or exchange plasmapheresis as therapy of choice has resulted in a dramatic increase in survival. By using more specific criteria than the classical clinical pentad, the diagnosis of thrombotic thrombocytopenic purpura during pregnancy can be made with greater accuracy. The first known instance of the successful use of exchange plasmapheresis leading to the survival of both mother and fetus in thrombotic thrombocytopenic purpura clearly not secondary to preeclampsia is reported. PMID- 4040620 TI - Comparing perinatal mortality. AB - Comparisons of perinatal outcome data among regions or hospitals can be misleading if the risk status of the population served is not considered. Data are presented from two large perinatal centers (Medical Center Hospital in San Antonio, Texas, and University of Iowa Hospitals in Iowa City, Iowa), which report substantially different institutional neonatal and fetal mortality rates. However, examination of neonatal and fetal mortality by birth weight groupings demonstrates the difference between outcome in the two hospitals to be considerably less than the overall rates might imply. Additional data about the regionalized system of care in Iowa are presented to illustrate why mortality may rise in a referral center and yet be consistent with a salutary effect on perinatal outcome in the region. PMID- 4040621 TI - Urodynamics: effect of urinary tract infection on urethral and bladder function. AB - To determine the accuracy and reliability of urodynamic studies performed during the course of unsuspected but significant lower urinary tract infection (greater than or equal to 10(5) organisms per mL), all the studies were repeated two and four weeks after successful treatment of urinary tract infection. Among 45% of patients (nine of 20) found to have unstable bladder before treatment of urinary infection, 60% of them (six of nine) regained bladder stability after appropriate treatment. Similarly, 30% of stress incontinent patients became continent after treatment of urinary infection and did not need surgery for correction of stress incontinence. Because of the high incidence of false-positive results of urodynamic studies when performed during infection (P less than .05), definite treatment of urinary incontinence should not be undertaken before successful treatment of urinary tract infection and repeating urodynamic studies in patients with persistent lower urinary tract symptoms. PMID- 4040622 TI - Cis-platinum, doxorubicin, and methotrexate treatment for recurrent cervical cancer. AB - A combination of cis-platinum, doxorubicin (Adriamycin), and methotrexate was used to treat 28 patients with recurrent cervical cancer. Seven patients achieved a partial response with a median duration of ten months. Two patients achieved a complete response with a median duration of 14 months. The overall response rate was 32%. Ten patients with stable disease had a median progression-free interval of 4.5 months. Toxicity was acceptable. PMID- 4040623 TI - Recurrent thrombotic thrombocytopenic purpura in early pregnancy: effect of uterine evacuation. AB - A 29-year-old woman developed thrombotic thrombocytopenic purpura on two occasions, each with onset at about the 13th week of gestation. Despite therapy during each episode with corticosteroids, platelet aggregation-modifying agents and repeated plasmapheresis, she experienced only transient improvement. In both instances, however, prompt hematologic recovery followed evacuation of the uterus. During an 18-month interval between pregnancies, her blood count remained normal and she continues in remission. The authors suggest that when thrombotic thrombocytopenic purpura appears in early pregnancy and its response to conventional management is minimal, immediate evacuation of the uterus may be an effective therapeutic alternative. PMID- 4040624 TI - Carbon dioxide laser treatment of cervical intraepithelial neoplasia. PMID- 4040625 TI - Diurnal intraocular pressure. Correlation to automated perimetry. AB - Patients referred to a centralized glaucoma laboratory obtained intraocular pressure measurements every two hours from 5:00 am to 3:00 pm. Analysis revealed 400 eyes with visual field defects and 400 eyes without visual field defects as determined by Octopus perimetry of the central 20 degrees. The diurnal variation in intraocular pressure was 6.2 mmHg +/- 3.6 for those with visual field defects and 5.5 mmHg +/- 2.7 for those without visual field defects. There was no statistical significance in the mean diurnal variation between the two groups (P = 0.91). The highest intraocular pressure tended to occur at either 5:00 am to 7:00 am or 11:00 am to 1:00 pm in both groups. The lowest intraocular pressure tended to occur between 7:00 am to 9:00 am or 1:00 pm to 3:00 pm in both groups. No significant differences were noted in the distribution between the two groups with regard to the time of the highest or lowest intraocular pressure. In the group with visual field defects, 30% had an intraocular pressure of less than 23 mmHg and 23% had an intraocular pressure of greater than or equal to 23 mmHg at all five time periods. PMID- 4040626 TI - Immunoglobulin E in mucoid secretory otitis media. AB - 19 serum and 23 middle ear mucoid fluid samples from patients with chronic secretory otitis media (SOM) were analyzed for total IgE using the PRIST technique and for specific IgE against dog epithelium, house dust mite, milk, egg white and wheat using the RAST technique. All serum samples showed IgE values well within the normal range, and the middle ear fluid-serum ratio for total IgE was less than 1. In three sera there was a weak (score 1) positive RAST result to milk (2 cases) and to egg-white (1 case). None of the middle ear fluids showed positive reactions. Routine clinical assessment of total and specific IgE is not indicated in SOM. PMID- 4040627 TI - Effect of environmental hypothermia on vitelline artery blood pressure and vascular resistance in the stage 18, 21, and 24 chick embryo. AB - We studied the effect of environmental hypothermia on arterial blood pressure, dorsal aortic blood flow, and vascular resistance in stage 18, 21, and 24 chick embryos. The arterial pressure was measured with a servonull micropressure system. Mean dorsal aortic blood flow was calculated from pulsed-Doppler measurement of mean dorsal aortic blood velocity and dorsal aortic diameter. Vascular resistance was calculated by dividing mean vitelline arterial blood pressure by dorsal aortic blood flow. Sequential data were obtained at temperatures of 34.7, 31.1, and 34.1 degrees C. At stage 21, the vitelline arterial blood pressure decreased from 0.82 +/- 0.03 (means +/- SEM) to 0.72 +/- 0.03 mm Hg on cooling and increased from 0.66 +/- 0.05 to 0.87 +/- 0.06 mm Hg on rewarming (p less than 0.05). At stage 21, mean dorsal aortic blood flow decreased from 0.49 +/- 0.02 to 0.33 +/- 0.02 mm3/s with cooling and increased from 0.34 +/- 0.02 to 0.47 +/- 0.02 mm3/s with rewarming. The vascular resistance in stage 21 embryos increased after cooling from 1.68 +/- 0.19 to 2.23 +/- 0.39 mm Hg/mm3/s (means +/- 95% confidence interval). The changes were similar in stage 18 and 24 embryos. We conclude that the reduction of vitelline artery blood pressure resulted from a decrease in cardiac output. In addition, we noted that the vitelline arterial vascular bed can constrict in response to hypothermia prior to autonomic innervation. These changes in hemodynamics may be a teratogenic mechanism for hypothermia-induced cardiac defects in the chick embryo. PMID- 4040628 TI - The effects of brain blood flow on brain bilirubin deposition in newborn piglets. AB - Since kernicteric lesions are usually found in the subcortical regions of the brain and these areas also receive the highest blood flow during asphyxia and hypercapnia, we hypothesized that increases in brain bilirubin deposition may be related to increases in brain blood flow. Fourteen piglets underwent a 3-h infusion of bilirubin to maintain total serum bilirubin at approximately 8 mg/dl, during which time blood gases, hemodynamic variables, and brain blood flow were determined. After sacrificing the animals, regional brain bilirubin content was determined. Ten piglets underwent the same protocol; in addition, hypercapnia was induced during the last hour of study (PaCO2 approximately 70 mm Hg). The regional brain blood flow and bilirubin deposition were significantly increased over control values (p less than 0.05) following hypercapnia in the subcortical region and significantly so in the midbrain and cerebellum. In separate groups of control (n = 6) and hypercapnia (n = 6) piglets, 125I-labeled albumin was infused and demonstrated that hypercapnia was not associated with increased regional brain albumin content. We conclude that hypercapnia-induced augmentation in regional brain blood flow is associated with increased deposition brain blood flow is associated with increased deposition of unbound bilirubin. Although the causal relationship between these two observations has not been firmly established, the findings deserve future investigation to clarify the role of brain blood flow, brain bilirubin deposition, and the production of kernicterus in high risk infants. PMID- 4040629 TI - To tube or not to tube: that continues to be the question. PMID- 4040631 TI - The importance of tumor markers in oral pathology. II. Cell membrane and cytoplasmic antigens as tumour markers. AB - Important tumour markers in tumours of the oral mucosa and salivary glands are intermediate filaments of cytoskeleton, oncofetal and proliferative antigens, lectin receptors and blood group substances, enzymes, metalloproteins and viral antigens. The special occurrence of the following tumour markers was demonstrated: keratin, vimentin, carcinoembryonic antigen (CEA), tissue polypeptide antigen (TPA), lectins (helix pomatia antigen = HPA, peanut agglutinin = PNA), Thomsen-Friedenreich-antigen, blood group substances A and B, amylase, lactoferrin, viral antigens of papilloma virus (group 11 and 16). In oral dysplasia and squamous cell carcinomas, relationships exist between the presence of keratin filaments and cell differentiation. Lectins represent membrane-orientated markers of differentiation. A loss of blood group substances A and B can be observed in oral dysplasias. Papilloma viruses and viral antibodies can be demonstrated in papillomas, leukoplakias and carcinomas. The salivary gland tumours show a distinct pattern of distribution for keratin, vimentin, CEA, TPA, metalloproteins and enzymes. Transplanted human salivary gland tumours in athymic nude mice keep the same tumour marker profile as in the primary tumor. PMID- 4040630 TI - Adenovirus DNA replication in vitro: site-directed mutagenesis of the nuclear factor I binding site of the Ad2 origin. AB - The template requirements for efficient adenovirus DNA replication were studied in vitro in a reconstituted system with cloned DNA fragments, containing the Ad2 origin region, as templates. Replication is enhanced by nuclear factor I, a cellular protein that binds specifically to the Ad2 origin. This stimulation is shown to be strongly dependent on the concentration of the adenovirus DNA binding protein. Using synthetic oligonucleotides we have constructed plasmids with base substitutions in the nuclear factor I binding region. Footprint analysis and competition filter binding studies show that two of the three small blocks of conserved nucleotides in this region are involved in the binding of nuclear factor I. The binding affinity can be influenced by the base composition of the degenerate region just outside these two blocks. In vitro initiation and DNA chain elongation experiments with the mutants demonstrate that binding of nuclear factor I to the Ad2 origin is necessary for stimulation. However, binding alone is not always sufficient since a mutation which only slightly disturbs binding is strongly impaired in stimulation of DNA replication by nuclear factor I. PMID- 4040632 TI - Galactorrhoea amenorrhoea syndrome due to internal carotid artery aneurysm. AB - A 32 year old female with hyperprolactinaemia-galactorrhoea-amenorrhoea due to a right internal carotid artery aneurysm just before its bifurcation is described. She had two episodes of subarachnoid haemorrhage necessitating an emergency internal carotid artery ligation. She responded to bromocriptine treatment with restoration of her menses, normalization of circulating prolactin and disappearance of galactorrhoea. PMID- 4040633 TI - Periductal mastitis and mammary duct ectasia in a male. AB - A case of periductal mastitis and mammary duct ectasia is presented in a 50 year old male, with presenting symptoms similar to those of females, namely subareolar breast lump and mastalgia. As far as can be ascertained only 4 cases of mammary duct ectasia and periductal mastitis in males have been reported previously. Since this entity is not well known in males it is possible that it may be underdiagnosed or misdiagnosed clinically and histologically. PMID- 4040634 TI - Spontaneous perforation of a pyometra presenting as generalized peritonitis. AB - Eleven cases of spontaneous perforation of a pyometra have previously been reported. All were associated with, and probably secondary to, cervical occlusion. A further case is described, but differs in that the cervical canal was patent. In the absence of other possible causes of uterine perforation, the aetiology of the perforation in this case remains uncertain. PMID- 4040635 TI - Effect of a failure of energy supply on adenine nucleotide breakdown in placentae and other fetal tissues from rat and guinea pig. AB - The effects of ischaemia on adenylate energy charge of tissues from fetal rats and fetal guinea pigs were measured. Adult rat and guinea-pig tissues, as well as human placentae, were also studied. The largest differences observed were between the fetuses from different pregnant animals (P = 4.74 X 10(-15). Reductions in energy charge in placentae were slower than in other defined fetal tissues, especially brain. In the rat, an immature species at birth, greater 'stability' was observed in placentae of 14 days of gestation than near term at 20 days of gestation. As contrast, in the guinea pig, a mature species at birth, there was no difference in 'stability' in placenta or other fetal tissues between about 40 days of gestation and near term, about 60 days of gestation. In addition to these tissue and maturity effects in the fetus, it has been confirmed that fetal tissues are more 'resistant' than adult tissues to failures of energy supply. Concentrations of adenosine, uridine, guanosine and cytidine nucleotides in placenta show similar patterns in rats and guinea pigs. Fetal liver contains more uridine nucleotides and brain more cytidine nucleotides. It is suggested that the placenta retains an early fetal ability to maintain itself during ischaemia; this might be advantageous during parturition. Possible endocrine and other mechanisms 'damping' fetoplacental metabolism are linked with a discussion of the large maternal effect. PMID- 4040636 TI - Metabolism of 1-nitropyrene and 6-nitrobenzo(a)pyrene by intestinal microflora. PMID- 4040637 TI - The future of germfree research. PMID- 4040638 TI - Indomethacin facilitates acute tolerance to and dependence upon morphine as measured by changes in fixed-ratio behavior and rectal temperature in rats. AB - The effects of indomethacin, a prostaglandin (PG) synthetase inhibitor, on acute tolerance to and dependence on morphine were investigated. Twelve mature, male Long-Evans rats were trained to lever press for food reinforcement on a fixed ratio 30 schedule (FR 30 behavior) and have their rectal temperature taken. The experimental protocol began with taking the rat's temperature followed by a 30 minute behavioral session. Immediately after this session the animal was injected with indomethacin or its vehicle. Two-and-a-half hours later this procedure was repeated, except that morphine or saline was administered. After an additional 2.5 hours had elapsed, a 60 minute behavioral session occurred. Half-way through the session the rat was injected with morphine (tolerance), naloxone (dependence), or saline. Immediately after the session the rat's temperature was recorded. Indomethacin potentiated the acute tolerance to the behavioral suppressant and hyperthermic effects of morphine. Indomethacin pretreatment also greatly enhanced the capacity of naloxone to decrease temperature and suppress FR 30 behavior in morphine-treated rats. These effects were not due to indomethacin altering the acute effects of morphine or the amount of morphine in the brain. These data suggest that indomethacin is inhibiting synthesis of PGs which are important in morphine tolerance and dependence. PMID- 4040639 TI - Barbiturate tolerance and dependence: effects on synaptosomal sodium transport and membrane fluidity. AB - DBA mice were fed lab chow containing phenobarbital for seven or eight days. Upon withdrawal of the phenobarbital diet, dependence was evidenced by appearance of hypothermia, handling-induced convulsions and lethal seizures. Functional tolerance was determined by injecting phenobarbital into mice treated with the phenobarbital diet or a pair-fed control diet and measuring the brain concentration of phenobarbital at the time of loss of righting reflex and the time of regaining righting reflex. Both measures demonstrated that chronic consumption of phenobarbital resulted in functional tolerance. When the diet was withdrawn for two days, tolerance was no longer present, indicating a rapid reversal of the adaptive changes. The veratridine-stimulated uptake of 24Na by isolated brain synaptosomes was used as a measure of membrane function. Sodium uptake was inhibited in vitro by pentobarbital and ethanol, and the inhibitory effects of these drugs were attenuated by chronic in vivo phenobarbital treatment. The fluidity of brain synaptic plasma membranes was estimated by the fluorescence polarization of the fluorescent probe molecules 1-(4 trimethylammonium phenyl)-6-phenyl-1,3,5-hexatriene and 1,6-diphenyl-1,3,5 hexatriene. Synaptic membranes from mice treated chronically with phenobarbital did not differ from those of control mice with regard to either the baseline fluorescence polarization of the probes or the decrease in fluorescence polarization produced by in vitro exposure to phenobarbital or ethanol. Taken together, these results indicate that although chronic phenobarbital ingestion resulted in tolerance and dependence (studied in vivo), and adaptation of sodium channels (studied in vitro), there was no evidence that these changes were due to alterations in the membrane physical properties. PMID- 4040640 TI - Effects of dose rate and dose fractionation of irradiation on pulmonary alveolar macrophage colony-forming cells. AB - We have studied the effects of dose rate and dose fractionation on murine pulmonary alveolar macrophage colony-forming cells (AL-CFC). The dose-response curve of AL-CFC to ionizing irradiation has a Dq of about 100 rad, reflecting the cells' ability to repair sublethal damage. For comparison, we investigated the effect of dose schedule on the committed bone marrow stem cells for both granulocytes and monocytes (GM-CFC) since their dose-response curve has a very small shoulder. We compared the results of dose rates of 3 and 10 rad/min to those obtained with a dose rate of 85 rad/min. We determined survival after giving 100, 300, and 500 rad either in vivo or in vitro. A significant dose rate effect was observed. To study the effect of dose fractionation, a total of 600 rad was given either as a single fraction, three fractions of 200 rad on 3 consecutive days, or six fractions of 100 rad in 3 days. The most dramatic effect was seen in the group that received six 100-rad fractions. No reduction in the number of AL-CFC was seen in this group. In sharp contrast, only a minimal dose schedule effect was observed with GM-CFC. PMID- 4040641 TI - [Effect of synthetic polyribonucleotides on the immunological and colony-forming activity of irradiated bone marrow cells]. AB - The experimental data are presented concerning the effect of polyribonucleotides on the immunologic and colony forming ability of bone marrow or irradiated mice. All the compounds under study exhibited a pronounced, but to a different degree, colony-forming and immunostimulating action. The comparative study of the influence of polyribonucleotides on the number of endogenous colonies and antibody-forming cells showed an inverse relationship between these parameters: The preparations exerting the most pronounced immunostimulating effect had an insignificant colony-forming action and vice versa. This is evidently indicative of the capacity of these preparations to turn the differentiation of haemopoietic stem cells towards the immunopoiesis. PMID- 4040642 TI - Voiding cystourethrography: the initial radiologic study in children with urinary tract infection. AB - The order in which children with urinary tract infection should undergo voiding cystourethrography (VCUG), excretory urography (EU), and/or renal ultrasonography (US) is not standardized. To determine a logical sequence of study, we performed VCUG and then either US or EU on 389 consecutive children with urinary tract infections. Thirty-seven percent (133/358) of the children were found to have reflux; of these, 22.5% (30/133) had an abnormal excretory urogram. No correlation was found between either the age of the child and the degree of reflux or the age of the child and the percentage of children with abnormal excretory urograms. Since normal EU or US results do not exclude significant reflux, VCUG is recommended as the preferred initial screening examination in children with urinary tract infection. PMID- 4040643 TI - Brain tumors: MR imaging with gadolinium-DTPA. AB - Magnetic resonance (MR) imaging was performed on 40 patients with intracranial tumors, before and after intravenous administration of gadolinium-DTPA (Gd-DTPA). Precontrast studies included a comprehensive protocol of spin-echo sequences. Tumors were visualized on precontrast images either directly or indirectly by anatomic distortion caused by the mass. However, differentiation of the tumor from adjacent tissues was possible in only 17 of 40 cases. Delineation of the tumor was best on precontrast, T2-weighted images. After administration of Gd DTPA (0.1 mmol/kg), increased signal intensity from the tumor was observed in all patients. The localized increase in signal intensity in the tumor considerably improved the tumor delineation in 36 of 40 patients. Whereas most of the meningiomas, neuromas, and adenomas could be delineated prior to administration of contrast material if appropriate pulse sequences were applied, glioblastomas and intracranial metastases required Gd-DTPA administration for diagnostically sufficient tumor display. PMID- 4040644 TI - Tumors and arteriovenous malformations of the spinal cord: assessment using MR. AB - Thirty-three patients with either primary spinal cord tumors (n = 18), intradural tumors excavating into the cord (n = 9), or spinal arteriovenous malformations (AVM) (n = 6) were studied with magnetic resonance (MR) imaging. In 25 of 38 examinations (66%) (five patients were studied twice), MR provided more information than that provided by other neuroradiologic procedures. In several cases, MR affected patient management decisions. Advantages of MR, in addition to the absence of ionizing radiation and its noninvasive nature, include good spinal cord-CSF-theca contrast, lack of bone-derived artifacts, ease of multiplanar imaging, improved discrimination between intra- and extramedullary lesions, better definition of tumoral cavities and possible distinction from true syringes, ability to help one recognize thrombus formation within an AVM, and ease of follow-up of cord lesions for possible size changes. Apart from factors precluding the study in several patients (life support systems, pacemakers, claustrophobia, neurovascular clips), disadvantages of MR imaging include motion artifacts (prevalent in thoracolumbar area), poor capability of typing and grading of tumors, potential of false-positive results, poor detection of calcification, and poor delineation of feeders and drainers of AVM. PMID- 4040645 TI - Changes in the affinity of [3H]nimodipine binding sites in the brain upon chlorpromazine treatment and subsequent withdrawal. AB - Male mice were chronically treated with chlorpromazine mixed in powdered diet, and the properties of brain calcium channels were assessed using [3H]nimodipine binding. It was found that this treatment resulted in a significant increase in the affinity of calcium channels, without a significant change in their density. These effects of chlorpromazine were time dependent. When mice were administered chlorpromazine for 2 months, then the drug was withdrawn, there was a rebound decrease in the channel affinity. PMID- 4040647 TI - [The depressed patient and his family]. PMID- 4040646 TI - [The effects of aging and genetic factors on heart rate response to hypoxia- studies in twins]. PMID- 4040648 TI - [Bologna's treatment method for stress urinary incontinence. An interesting technic in large cystoceles]. AB - The authors report a series of 25 operations using the Bologna technic in which 20 cases were examined with bladder function tests before and after surgery. This technic has curative results for vesical hernia or cystocele and urinary incontinence. In all but one case the abdominal pressure transmission defect to the upper urethra was corrected without deterioration of maximal urethral pressure. PMID- 4040649 TI - Perinatal mortality distributed by type of hospital in the Central Hospital District of Helsinki, Finland. AB - In Finland as in many other countries, perinatal mortality is higher in those institutions having a higher level of care. To explain this phenomenon, mortality by weight groups was studied in different hospitals in the Central Hospital District of Helsinki in Finland in 1977-81. Among infants weighing less than 2 500 g, perinatal mortality was higher in the local hospital than in the university hospital, the higher mortality being due to the higher rate of stillborn infants. Among babies weighing over 2 500 g, the mortality was lower in local hospitals than in the university hospital. Further studies to explain the higher mortality of infants weighing over 2 500 g in the university hospital are needed. PMID- 4040650 TI - [Prevention of mastitis-metritis-agalactia in sows of problem herds]. PMID- 4040651 TI - Ethanol withdrawal in mice precipitated and exacerbated by hyperbaric exposure. AB - Mice were fed an ethanol-containing liquid diet for 9 days. On removal of the diet, exposure to 12 atmospheres absolute of a mixture of helium and oxygen precipitated earlier withdrawal, increased withdrawal scores for the first 6 hours, and increased the peak withdrawal intensity compared to dependent animals exposed to control conditions. The enhanced withdrawal did not appear to reflect alterations in ethanol elimination, oxygen or helium partial pressures, body temperature, or general excitability. These results extend to chronically treated animals the evidence that hyperbaric exposure antagonizes the membrane actions of ethanol. PMID- 4040652 TI - A ten-year study of twins in Toa Payoh Hospital 1973-1982. PMID- 4040653 TI - Soft tissue abscess caused by Torulopsis glabrata and Lactobacillus. PMID- 4040654 TI - Humoral immune responses to soluble somatic extracts of Dipetalonema viteae adult worms infected hamsters. AB - The present study examined the serum IgG1 and IgM antibody responses of infected hamsters to unfractionated and fractionated soluble somatic (SS) antigens of adult Dipetalonema viteae. Male and female adult worms were homogenized in a French pressure cell and the SS proteins extracted with 0.375 M Tris-glycine buffer. Serum IgG1 and IgM antibody responses in D. viteae infected with LVG, PD4 and CB hamster strains to the male and female unfractionated SS proteins were measured by an indirect enzyme linked immunosorbent assay (ELISA). Serum IgG1 antibody responses to the SS proteins were similar in all three strains of hamsters during the course of infection. There was no correlation between the level of IgG1 antibody and the onset of microfilariae clearance. The serum IgM antibody response was similar in both outbred LVG and inbred PD4 hamster strains. A lower IgM antibody response was found in CB hamsters and could be related to the failure of this hamster strain to eliminate microfilariae. The SS proteins of male and female adult worms were fractionated by preparative flat-bed isoelectric focusing on granulated gels (PIEF) to yield 8 and 7 fractions, respectively. The comparative antigenicity of the PIEF fractions from the SS proteins was measured by ELISA, using hyperimmune serum from LVG hamsters and rabbit antihamster IgG1 and IgM-alkaline phosphatase conjugates. No difference in ELISA reactivity was noted among the 8 and 7 PIEF fractions from male and female SS proteins.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4040655 TI - Phaeoannellomyces and the Phaeococcomycetaceae, new dematiaceous blastomycete taxa. AB - Phaeoannellomyces McGinnis et Schell gen. nov., which is based upon P. elegans McGinnis et Schell sp. nov., is proposed for dematiaceous yeasts which produce percurrently proliferating conidiogenous cells. Cladosporium werneckii Horta is transferred to Phaeoannellomyces as P. werneckii (Horta) McGinnis et Schell comb. nov. because the most stable and distinctive synanamorph produced by this fungus consists of annellidic yeast cells. The Phaeococcomycetaceae McGinnis et Schell fam. nov. is proposed in the class Blastomycetes, division Fungi Imperfecti for the dematiaceous yeast genera Phaeoannellomyces and Phaeococcomyces de Hoog. PMID- 4040656 TI - Syrinx of the conus medullaris and filum terminale in association with multiple hemangioblastomas. AB - A patient with multiple hemangioblastomas and syrinxes of the cerebellum and spinal cord is presented. An additional mass imaged at the L-3 vertebral level was identified by percutaneous syringography as a bilobular syrinx extending from the conus medullaris into the filum terminale. At surgery the syrinx was opened into the caudal cerebrospinal fluid space and the several hemangioblastomas excised. These spinal tumors all appeared to arise in juxtaposition to the posterolateral sulcus and dorsal sensory roots. PMID- 4040657 TI - [Vascular component of the fibrinolytic system of blood (plasminogen activator of vascular wall) in patients with duodenal ulcer with a history of hemorrhagic complications]. AB - It has been established that patients with duodenal ulcer complicated by hemorrhage in the past are characterized by the low response of the fibrinolytic system (FS) to two different exposures--local venous occlusion and administration of the sympathomimetic alupent. The rate of plasminogen the lower limit of normal in almost 2/3 of patients with activator release (RPAR) from vascular depots was under hemorrhages and in 1/4 of those with uncomplicated duodenal ulcer. The low RPAR was coupled with hereditary aggravation and hyperplasia of the parietal glandulocytes of the stomach. In duodenal ulcer complicated by hemorrhages, the normal parameters of the fibrinolysis kinetics and RPAR were encountered 3 times less frequently than in uncomplicated duodenal ulcer, whereas activated blood fibrinolysis coupled with the low RPAR 5 times as frequently. The shifts can severe a discriminant prognostic criterion painting to a potential risk of hemorrhage and making it possible to carry out the different prophylaxis. The treatment with epsilon-aminocaprotic acid given in courses makes the FS including its vascular component return to normal. PMID- 4040658 TI - Characterization of two monoclonal antibodies against human tissue-type plasminogen activator. AB - A series of hybridoma clones, each producing monoclonal antibodies to human tissue-type plasminogen activator (t-PA), were prepared from mice by standard procedures. Two of these clones were selected for further study. One HI72A1, produced antibodies that bound to t-PA and strongly inhibited its activity, whereas another, LI72D1, produced antibodies that bound to t-PA but did not affect its activity. The specificity of these antibodies was assessed in immunoabsorption experiments. Both immunoprecipitated 125I-labeled t-PA, and both were specific since only t-PA was recognized in conditioned media collected from Bowes melanoma cells cultured in the presence of 3H-leucine. Neither antibody recognized urokinase. t-PA was desorbed from antibody HI72A1-Sepharose columns with 0.5 M NaCl, consistent with its relatively low association constant (Ka = 9.37 X 10(7) M-1). In contrast, a strong chaotropic agent (i.e., 2 M KI) was required to elute t-PA from antibody LI72D1 columns (Ka = 2.08 X 10(9) M-1). This latter high affinity antibody was employed to develop an immunoradiometric assay for t-PA having a sensitivity of 0.5 ng/ml. PMID- 4040659 TI - In vitro studies on the fibrinolytic, thrombolytic and fibrinogenolytic properties of a tissue plasminogen activator from guinea pig keratocytes. AB - The fibrinolytic and thrombolytic properties of a tissue plasminogen activator (tPA) purified from the conditioned medium of an established guinea pig keratocyte (GPK) cell line were investigated in in vitro systems and compared with urokinase. Using the fibrin clot lysis assay, GPK activator appears to be similar to human melanoma tPA and not to human urokinase. GPK activator also caused negligible fibrinogen breakdown, when incubated with human plasma at 37 degrees C over 23 hr. Urokinase on the other hand caused significant fibrinogenolysis, under similar conditions. Comparison of the lysis of plasma clots by GPK activator and human urokinase have shown that GPK activator was a much more effective fibrinolytic agent than urokinase, especially at lower concentrations (less than 50 IU/ml). Studies on the thrombolytic effect of GPK activator on the lysis of aged and cross-linked whole human blood clots and plasma clots hanging in artificially circulating human plasma suggest that GPK activator can lyse both these types of clots equally well. The lysis is dose dependent, attaining complete lysis within 3-6 hr with the concentration of GPK activator in the range of 1-5 micrograms/ml plasma. It is concluded that GPK activator has a higher fibrinolytic and thrombolytic activity and lower fibrinogenolytic activity than urokinase. PMID- 4040660 TI - Species specificity in the acceleration of tissue-type plasminogen activator mediated activation of plasminogens, by fibrinogen cyanogen bromide fragments. AB - Activation of human plasminogen by human tissue-type plasminogen activator (t-PA) is accelerated in the presence of cyanogen bromide digests of human fibrin(ogen). In the present study a possible species specificity of this phenomenon was investigated. All combinations of the plasminogens, fibrin monomers and cyanogen bromide digests of the fibrinogens of man, pig, rat, cat and monkey (Macaca mulatta), and three t-PA species (man, rat and pig) were studied. No species differences were noted with the fibrin monomers i.e. the activation rate of all five plasminogens increased more than 20-fold in the presence of all five fibrin monomer species, irrespective if man, rat or pig t-PA was used. However, we found that species specificities come to expression when cyanogen bromide digests of the corresponding fibrinogens were used as accelerators. Our results indicate that the plasminogen species and not the source of t-PA or fibrinogen dictates if accelerated activation occurs in the presence of a fibrinogen CNBr digest. The plasminogens can be roughly divided in two groups: --One group, comprising human, monkey and cat plasminogen, which are activated at a higher rate by all three t PA species in the presence of fibrinogen digest independent on the fibrinogen species from which the digest was prepared. --Another group, comprising pig and rat plasminogen, which is not or only marginally more quickly activated by the 3 t-PA species, irrespective of the fibrinogen species from which the CNBr digest was prepared. PMID- 4040661 TI - [Economic losses to farms due to paratuberculosis in cattle]. AB - The results of a study on economic losses to farms caused by paratuberculosis in dairy cattle are reported. Quantification of the decrease in production and determination of standard losses due to premature disposal using calculations based on a model were stressed. A decrease in production of 19.5 per cent compared with the last lactation but two was recorded in animals showing clinical symptoms of paratuberculosis. The decrease in production was 5 per cent during the last lactation but one compared with the previous lactation. The decrease in production during lactation on disposal was 16 per cent and 6 per cent during the last lactation but one compared with the last lactation but two in animals with non-clinical forms of paratuberculosis. The average cow showing clinical symptoms of paratuberculosis, which was disposed of, caused a total loss of 2,250 guilders, whereas the average cow with a non-clinical form of Johne's disease was estimated to cause a loss of 1,800 guilders. PMID- 4040662 TI - Diurnal variation of QT interval in patients with VVI pacemaker. AB - In nine patients with chronically implanted ventricular pacemaker (VVI), diurnal variation of the QT interval was studied. The mean age of the patients was 74.2 years and underlying diseases were atrioventricular block (three patients), sick sinus syndrome (four patients) and chronic atrial fibrillation with bradycardia and heart failure (two patients). Eight of the nine patients showed longer QT intervals during sleep than during waking. Only one patient showed no change in QT interval during sleep and during wake time. The mean QT interval of the nine patients at each hour was slightly longer (9 msec) during sleep than that during each awake hour (p less than 0.001). The prolongation of QT interval during sleep may offer a possible mechanism of some nocturnal arrhythmias. PMID- 4040663 TI - Antitumor effect of the yeast polysaccharide preparation in syngeneic mouse tumor models. AB - Antitumor effect of our Candida utilis glucomannan preparation (YPS) was evaluated in two syngeneic transplantable tumors; the Lewis lung carcinoma (3LL) in C57BL/6 (B6) mice and the 3-methylcholanthrene (MCA)-induced fibrosarcoma in C3H/He mice. YPS inhibited preferentially the 3LL pulmonary metastases only when optimal dosage was given at an earlier stage; 7 daily intraperitoneal (i.p.) doses of 100 mg/kg per dose from the next day of tumor inoculation (1 X 10(5)/mouse, subcutaneously, s.c.) substantially reduced the number of metastatic nodules, yielding the inhibition ratio 54% on day 21. However, the same treatment delayed until day 8 markedly facilitated the metastatic spread (-105%). Postsurgical-adjuvant therapy with YPS (10 daily i.p. doses of 100 mg/kg per dose from the next day of surgery) was effective in improving the survival rate with no evidence of metastatic growth on day 200, even though the amputation of the tumor-bearing legs was performed after the pulmonary metastases had been established (on day 20). In the MCA-fibrosarcoma model, YPS treatment from day 3 (10 daily doses of 100 mg/kg per dose) was effective in prolonging the survival period. The 3LL local tumor was affected only marginally and temporarily, while the MCA-tumor was not at all. PMID- 4040664 TI - Effects of prostaglandin E1 infusion in the pre-operative management of critical congenital heart disease. AB - Prostaglandin E1 (PGE1) was administered to 27 infants in whom pulmonary or systemic blood flow was entirely or significantly dependent upon the patency of the ductus arteriosus. In 12 patients with pulmonary atresia or severe pulmonary stenosis, PGE1 infusion was followed by an improvement in hypoxemia and acidemia (group I). In 2 patients with left ventricular outflow-tract obstruction, PGE1 infusion was followed by an improvement in arterial blood pressure, peripheral perfusion and urine output (group II). In 5 patients with d-transposition of the great arteries and intact ventricular septum who had persistent severe hypoxemia after creation of an interatrial communication, PGE1 infusion improved the arterial oxygenation with dilatation of the ductus arteriosus (group III). Seven patients (3 of group I, 2 of group II and 2 of group III) failed to respond to PGE1. There were no fatal side effects. It is concluded that PGE1 therapy is highly effective in stabilizing pre-operative conditions of infants with ductus dependent congenital heart disease. PMID- 4040665 TI - The effect of chronic ethanol ingestion on hepatic lipid peroxide, glutathione, glutathione peroxidase and glutathione transferase in rats. AB - Water containing 20% ethanol was given for a period of 3, 6 and 9 weeks to rats, and changes in hepatic lipid peroxide, glutathione, glutathione peroxidase and glutathione transferases were investigated. Lipid peroxide levels and glutathione peroxidase activities remained unchanged after 3 weeks and started to increase thereafter. Glutathione levels and glutathione transferase activities were significantly increased following ethanol consumption. These results show that chronic ethanol consumption stimulates hepatic lipid peroxidation in rats. This stimulation is not dependent on glutathione depletion and the increased glutathione peroxidase and glutathione transferase activities may reflect an adaptive change against ethanol-induced lipid peroxide toxicity. PMID- 4040666 TI - Ichthyotoxism by a paralytic toxin produced by marine dinoflagellates of the genus Ceratium: relationship to fraction beta isolated from the sponge Tedania ignis. AB - Two hundred tons of the plankton feeding sardine Cetengraulis edentulus died in March 1982, in Carenero (10 degrees 10' N, 66 degrees 05' W), Venezuela. A fraction was extracted from this fish that was toxic to mice by i.p. injection. The animals died in less than 4 min and showed generalized flaccid paralysis. Gel filtration on Sephadex G15 and Bio Gel P2 showed that the toxicity is related to a fraction that blocks the release of acetylcholine in frog (Rana pipiens) neuromuscular junctions. This toxin is similar in chemical properties and presynaptic effect to fraction beta isolated from the sponge T. ignis by Sevcik and Barboza. Fractions of the same biological action and chemical properties were isolated from plankton samples collected in the area of the ichthyotoxism. The correlation analysis between the presence of toxin and a plankton species in a sample, was carried out with a feasibility index (as %) defined by Sevcik and Mijares. Random samples of plankton (29) were collected in 3 locations (11 degrees 50' N, 68 degrees 15' W; 10 degrees 36' 24'' N, 67 degrees 14'7'' W and 10 degrees 21' N, 64 degrees 21' W). The correlation carried out over 167 species of phytoplankton present in the samples indicates that the species most likely to be responsible for the production of the fraction beta, in order of feasibility index (in parentheses) are: Ceratium furca (54%), Protoperidinium sp. (1.7%) and Protoperidinium pallidum (1.6%). In some samples a fraction similar to fraction alpha from T. ignis was also found. The identification of the phytoplankton responsible for this fraction is, however, less conclusive. The feasibility indexes are: Protoperidinium sp. (58%), Ceratium inflatum (30%), Podolampas sp. (23%), Ornithocercus steini (21%). The genus Ceratium was the second most abundant in Carenero at the time of the fish death. These results suggest that the toxins isolated from C. edentulus and T. ignis have a planktonic origin. PMID- 4040667 TI - Distribution of paralytic toxins in California shellfish. AB - Samples of Saxidomus nuttali and Mytilus californianus collected during the 1981 dinoflagellate bloom at Bodega Bay, California, were analyzed for the presence of paralytic toxins. Neck tissue of S. nuttali contained saxitoxin (STX) and neoSTX (95% of the total toxicity), whereas the bodies contained neoSTX and a mixture of the gonyautoxins. In a sample of M. californianus the presence of neoSTX and the gonyautoxins was demonstrated, whereas a second sample, collected at a different site, contained almost exclusively neoSTX. PMID- 4040668 TI - Brevetoxins: chemistry and pharmacology of 'red tide' toxins from Ptychodiscus brevis (formerly Gymnodinium breve). PMID- 4040669 TI - Effects of crude brevetoxin on membrane potential and spontaneous or evoked end plate potentials in rat hemidiaphragm. AB - The principal effects of crude brevetoxins on the neuromuscular junction of rat phrenic--diaphragm preparations are to: preferentially depress indirectly induced muscle contractions at concentrations lower than those required to affect directly induced muscle contractions; depolarize muscle membrane at both synaptic and extra-synaptic areas; increase MEPP frequency and eventually block end-plate potential generation; induce a concentration dependent biphasic effect on MEPP amplitude; depress acetylcholine-induced depolarizations. The mechanism of muscle membrane depolarization appears to involve an increase in membrane permeability, as shown by a decrease in input resistance at both synaptic and non-synaptic areas. That the major change is in sodium ion permeability is indicated by the observations that depolarizations do not occur in the absence of extracellular sodium or in the presence of tetrodotoxin, a sodium channel blocker. PMID- 4040670 TI - Cardiovascular effects of brevetoxins in dogs. AB - In anesthetized spontaneously breathing dogs, brevetoxin caused dose-dependent periods of apnea and, at high doses, respiratory arrest. In artificially ventilated dogs, i.v. brevetoxin caused complex dose-related cardiovascular changes consisting of: (1) bradycardia; (2) triphasic blood pressure changes, sequentially characterized by depressor/pressor/depressor phases; (3) cardiac arrhythmias including ventricular fibrillation; (4) muscle fasciculations. Prevention of bradycardia by atropine, vagotomy or ganglionic blockage unmasked a tachycardic action of the toxin. Ganglionic blockade, but not atropine or vagotomy, reduced the initial depressor effect of toxin. Phentolamine prevented the toxin-induced initial hypotension and secondary hypertension. Propranolol prevented the tachycardic and late depressor effects of toxin. In reserpinized dogs, low doses of toxin caused muscle fasciculations but none of the above cardiovascular effects; large doses caused bradycardia preventable by atropine, but not by vagotomy or chlorisondamine. These results suggest that brevetoxin: elicits the Bezold-Jarisch effect, i.e. initial hypotension, bradycardia and apnea; releases catecholamines, probably adrenal epinephrine, causing tachycardic, secondary pressor and late depressor effects; in large doses, releases vagal acetylcholine; -induced catecholamine and acetylcholine release is not nicotinic; produces effects, like those reported for veratridine, attributable to a common action on excitable membranes. PMID- 4040671 TI - Adenylate cyclase and histopathological changes in the gerbil brain following prolonged unilateral ischemia and recirculation. AB - This study was designed to correlate histopathological changes in gerbil brain following unilateral primary and secondary ischemia to enzymatic-adenylate cyclase damage. At three hrs permanent occlusion of the right common carotid artery only minimal histological changes were evident in cerebrum, hippocampus, striatum and olfactory tubercle while the enzyme responses were unremarkable. Severe histological and enzymatic alterations were present at one hour of recirculation subsequent to 3 hrs of unilateral occlusion. Similar damage was evident at 6 and 24 hrs permanent occlusion. Principal enzyme damage was directed toward basal activity, as well as stimulation of the catalytic (forskolin sensitive) sites on the enzyme complex. For the most part the transducer (GTP sensitive) site was unaffected by ischemia until 24 hr ligation. These changes were observed in only those gerbils developing severe symptoms of stroke. PMID- 4040672 TI - Enhancement of the immunosuppressive effect of graft-versus-host disease by partial-body irradiation. PMID- 4040673 TI - Accuracy of the double contrast enema in evaluation of the abdominal diffusion of ovarian carcinoma. AB - The results of 103 double contrast enemas in 72 patients with ovarian carcinoma (stage III and IV) were compared with laparoscopic and/or laparotomic findings at comparable times. The evaluation of the validity of radiology in detecting the presence of abdominal disease showed an 84% overall accuracy, 75% specificity and 86% sensitivity. The accuracy in detecting signs of adhesion and parietal infiltration of the large bowel was 76.3%, due to the limited size of most of the lesions. Forty-seven of the 72 patients underwent a double contrast enema and laparoscopy during presurgical staging: accuracy in detecting lesions was the same for both examinations (80.4%). When double contrast enema and laparoscopy were used together in the evaluation of abdominal extension of the disease, the diagnostic accuracy rose to 93.6%. PMID- 4040674 TI - [Properties of cathepsin D from unfertilized eggs, embryos and skeletal muscles of the loach]. AB - The action and some properties of cathepsin D, partly purified from unfertilized loach eggs, embryos and skeletal muscles were determined. The enzyme from embryo cells displays the activity maximum at pH 3.0 and pH 4.8 while enzyme from skeletal muscles--only at pH 3.0. Cathepsin D purified from all three sources splits actively hemoglobin, albumin, alpha-glycerophosphate dehydrogenase, pyruvate kinase and practically does not influence casein, hexokinase, glucose-6 phosphate dehydrogenase. The enzyme is comparatively thermolabile and its activity decreases in the presence of thiol compounds. The main part of cathepsin D in skeletal muscle cells and in embryo cells is precipitated after differential centrifugation of homogenates (25000 g; 60 min). PMID- 4040675 TI - [Leucine aminopeptidase activity in pain-induced emotional stress]. AB - It is established that leucine aminopeptidase activity during emotional-algesic stress increases in the brain hemispheres, left ventricle and liver of the rats as compared to that of intact animals. Maximum activation of the enzyme in the brain and liver is detected for the first two days after the stress while in the heart - for the whole period of the total stress damages volume development. A conclusion is drawn that the shifts observed in leucine aminopeptidase activity during emotional-algesic stress affect the methionine-enkephalin and leucin enkephalin ratio. PMID- 4040676 TI - Segmental aplasia and hydrometra in a goat. PMID- 4040677 TI - [Prevention of impairment of myocardium metabolism and function in immobilization stress using previous adaptation to short stress exposures]. AB - A long-term immobilization stress was shown to cause a distinct enzymemia in rats. Simultaneously, activation of lipid peroxidation and a decrease in glycogen content were observed in myocardium; a distinctly increased penetration of aspartate transferase, lactate- and malate dehydrogenases and RNAase into coronary circulation was found in isolated heart of the animals. These impairments of metabolism were accompanied by a depression of the heart contractile function. The impairments in metabolism and in heart functions might be prevented by preadaptation of the animals to multiple short-term immobilization effects, which did not cause any impairments per se. PMID- 4040678 TI - [Energy metabolism in the cerebral cortex in necrosis of the myocardium]. AB - In ischemic necrosis of myocardium inhibition of energy metabolism occurred in brain, as a result of which an impairment of the brain functional state might take place. Emotional stress, preceding the myocardium necrosis, augmented the impairments of energy metabolism in brain hemispheres. PMID- 4040679 TI - [Use of antioxidants for the prevention and correction of the negative effects of hypokinesia]. PMID- 4040680 TI - [The use of lasers in medicine with special reference to dermatology]. AB - The laser machine and the unique quality of the laser beam are described. The basis of the medical application of laser is its capacity to concentrate large amounts of energy on a small volume of tissue, mostly resulting in thermal coagulation necrosis. The effect of monochromate laser radiation varies, depending on the different absorption of various laser beams by tissues. Indications of various types of lasers for treatment, especially in dermatology, are discussed and safety instructions are mentioned. PMID- 4040681 TI - [Clinical pharmacology of nonsteroidal antiphlogistics. II: Interactions and side effects]. PMID- 4040682 TI - [Edemas--review of pathogenesis]. PMID- 4040683 TI - [Fine structure of the uterine gland epithelium in cattle]. PMID- 4040684 TI - The influence of congenital Toxoplasma infection on the spontaneous running activity of mice. AB - Home-cage running-wheel activity of mice congenitally infected with Toxoplasma was recorded over 24 days. Infected mice were consistently more active than uninfected controls over the entire testing period. This finding extends previous studies and indicates that such increased activity levels occur not only in novel but also in familiar environments, and suggests that congenital toxoplasmosis tends to render mice "hyperactive'. If such behavioural alterations occur in wild mice, it is likely that infected mouse intermediate hosts would be more susceptible to predation by cats, the definitive hosts of Toxoplasma. PMID- 4040685 TI - Human adenovirus 2 as immunogen in rabbits yields antisera with high titers of antibodies against the nonstructural 72K DNA-binding protein. AB - Immunization in rabbits with intact, highly purified adenovirus type 2 (Ad2) virions, yielded antisera with high titers of antibodies against the 72 000 dalton DNA-binding protein (DBP). This was established by rocket immunoelectrophoresis when an anti-intact Ad2-antiserum was analyzed against fractions from an ion-exchange chromatogram of soluble antigens remaining after virus isolation from virus-infected HeLa cells. The high anti-DBP titer did not reflect the composition of the immunogen, since no DBP was detectable within virions. An antiserum raised in response to mildly disrupted virions showed no specificity against the DBP, but contained antibodies against the same structural proteins as the anti-intact Ad2-antiserum, when analyzed by the immunoblotting technique. These findings indicate that the nonpermissive rabbit as an experimental host permits early gene expression of a human adenovirus. PMID- 4040686 TI - [Participation of angiotensin II in the establishment of negative emotional reactions]. AB - In waking rats and rabbits systemically injected angiotensin II was shown to participate predominantly in the mechanisms of negative emotional reactions. The effects of angiotensin II were observed at the behavioural level as well as at the neuronal one. Depending on the dose and the time of injection of angiotensin II and its specific antagonist saralasin they inhibited or facilitated elaboration and extinction of automatized conditioned active avoidance independently of arterial, pressure changes, the pain threshold being altered. Injection of angiotensin II abolished individual behavioural reactions of the animals in response to stress factors and increased their resistability to emotional stress. The negative emotional reactions were found to induce changes of chemosensitivity of neurones of the parafascicular complex of the medial thalamus and the midbrain reticular formation during microionophoretic application of angiotensin II. A supposition is made about the increase of angiotensin II brain synthesis under conditions of emotional stress. PMID- 4040687 TI - [Development of passivity in the rat: effect of tranquilizers and antidepressants]. AB - Following the views on passivity as one of the features of depression-like behaviour in rats developing as a result of unavoidable painful stimulation an attempt was made to eliminate by antidepressant drugs the passivity manifested in an almost complete absence of motor searching reactions in an "open field" and a maze. However tranquilizing drugs rather than antidepressants to a greater extent induced the effect presupposed. Hence the type of passivity under study corresponds more likely to neurotized behaviour than to a special depression like. In the second series of experiments the action was studied of multiple injections of antidepressants on similar manifestations of passivity as well as on alimentary instrumental conditioned responses in rats with initially expressed passive character of behaviour. In this case too neither the presupposed increase of motor searching reaction was observed nor any significant changes in the rate of instrumental conditioning nor elimination of its failures of a "refuse" type. PMID- 4040689 TI - [PQ interval and pre-excitation syndrome in direct fetal electrocardiogram--fetal Lown-Ganong-Levine (LGL) syndrome]. AB - Preexcitation syndromes are rare disturbances of the atrioventricular excitation transmission in direct fetal electrocardiograms. As example we report on a fetal Lown-Ganong-Levine (LGL)-syndrome. This is to differentiate from the Wolff Parkinson-White (WPW)-syndrome, which is possible by typical changes in the QRS complex. Possibly the short PQ-interval in the fetal electrocardiogram is functional, but needs postnatal control. PMID- 4040688 TI - [Role of limbic-neocortical mechanisms in the formation of experimental alcoholism in the rat]. AB - The role of the amigdalar complex and the hippocampus as well as their interaction with the hypothalamus in a formation of attraction to alcohol was studied in 40 rats. After electrolytic lesions of the hippocampus and the amigdalar complex at early stages of alcoholization the inhibition of development of this pathologic attraction occurred however with subsequent dynamical reorganization of the structural and functional mechanisms of alcoholic motivation and with duplication of the triggering links. Important role of the limbico-neocortical relations was revealed in a development of behavioural and emotional-vegetative disturbances accompanying experimental alcoholism. PMID- 4040690 TI - Immunological and virological studies of patients with tumours of the urogenital system. AB - The possible connections between the oncogenic viruses and the various tumours of the urogenital system were investigated. Examining the patients' cellular immune response by the lymphocyte transformation test, it was found that the non specific immune response was considerably diminished in almost all cases, while response to adeno- and herpesvirus antigens was enhanced. Structural and functional impairment of T-lymphocytes frequently occurred. Antiviral humoral antibodies were present more rarely in cancer patients than in the controls. However, type 12 markedly oncogenic anti-adenovirus antibody was frequently found. Using the immunofluorescent method, adeno- and herpesviruses were found in more than 50% of the patients' malignant tumour cells. Electron microscopically, in some cases adeno-, herpes- and type C virus particles, too, were isolated in the tumour cells. According to these results besides other factors also adenoviruses may play a role in urogenital tumours. PMID- 4040691 TI - Sexual behaviour in a centre for epilepsy. AB - The sexual behaviour and hormonal profiles in 97 patients with chronic epilepsy from an epilepsy centre were studied. Sexual behaviour relating to numbers of sexual contacts, orgasms, spontaneous erections, and early morning erections, whether there was difficulty in obtaining or maintaining an erection, or in ejaculation, was assessed at interview. Hormonal profiles consisted of LH, FSH, prolactin, total testosterone, free testosterone, and SHBG. Information was obtained relating to type of seizure, seizure frequency, age of onset, likely pathology, IQ, and medication. The study showed that this patient group was profoundly hyposexual and had a high level of sexual dysfunction. Serum free testosterone levels were low, and it is suggested that the high level of sexual dysfunction and lack of sexual interest may well have a hormonal basis. The reasons for this are discussed. PMID- 4040692 TI - X-linked bulbo-spinal neuronopathy of late onset. AB - Two cases of X-linked bulbo-spinal neuronopathy (BSN) of late onset are presented. An extensive review of the literature shows that, in addition to the signs of a chronic degeneration of brainstem and spinal neurons, other clinical features may also be present at the onset of the disease, or develop during its course. Some clinical, electrophysiological and anatomical data support the hypothesis that BSN is not purely a motoneuronopathy but also concerns sensory nerve. PMID- 4040693 TI - Hemangioblastomas with cystic stromal cell nuclei. AB - Clearing of stromal cell nuclei were found in two of a series of nine cases of hemangioblastoma. The contents of the clear zones were often positive for lipoprotein by immunoperoxidase staining which suggested that the contents originated from the cytoplasm. Cytoplasmic invagination was not observed but is probable; some vacuoles had a "bubbly" appearance similar to the lipid-laden cytoplasm. The finding of these variations in two of nine cases suggests that cystic change in stromal cell nuclei may not be uncommon in hemangioblastomas. PMID- 4040694 TI - Alexander's disease. AB - This is the first pathologic report of an infant at 37 weeks' gestation with Alexander's disease. The findings demonstrate that the disease can arise in utero and be extensive at birth before myelination begins. PMID- 4040695 TI - Ultrastructure of cerebellar hemangioblastoma. Some new observations on the stromal cells. AB - Five cases of hemangioblastoma were studied by electron microscopy with particular attention to the stromal cells and their surrounding structures. Most of the stromal cells of the tumor had abundant clear cytoplasm containing rough endoplasmic reticulum, mitochondria, scattered fibrils, and large lipid inclusions. They were usually aggregated without intervening cells. In the perivascular areas, their surfaces facing the perivascular collagen were surrounded by basal lamina. Their apposed cell membranes had occasional adhesive devices. Occasional, long, apparently cylindrical processes of the stromal cell cytoplasm were observed in some cases. These processes contained intermediate filaments of undetermined nature and microtubules. In the border zone between the tumor and the surrounding brain, the stromal cells were occasionally surrounded by narrow sheets of dark cell processes containing fibrils and glycogen granules, consistent with astrocytic processes. Altered neuronal elements were also observed in this area. PMID- 4040696 TI - Electrocochleographic changes in the hearing loss associated with X-linked hypophosphataemic osteomalacia. AB - Transtympanic electrocochleography was carried out on 13 patients (21 ears) suffering from X-linked hypophosphataemic osteomalacia, and known to have cochlear hearing loss. The majority of ears exhibited a cochlear pattern of cochleogram with a recruiting input/output function and a markedly biphasic action potential. In addition 14 ears yielded a greatly enhanced negative summating potential, suggesting the presence of endolymphatic hydrops. It is proposed that the hearing loss so frequently associated with this condition is in part due to endolymphatic hydrops. PMID- 4040697 TI - Endotoxin in middle ear effusions tested with Limulus assay. AB - Endotoxin in middle ear effusion (MEE) from both children and adult patients with otitis media with effusion (OME) was assayed with the Limulus amoebocyte lysate test, in parallel with the detection of microorganisms. Whereas only 17% of MEE from adults, diluted 1:10 showed the presence of endotoxin, endotoxin was found in 69% of MEE from recent and recurrent cases in children, although microorganisms were isolated from only one-quarter of the samples. 83% of mucoid MEE from children contained endotoxin, compared with 41% of serous MEE. In older children, endotoxin was less frequently detected in accordance with the fact that the incidence of OME decreases with age. It is concluded that endotoxin may be one of the important factors in the pathogenesis of onset of, as well as in delayed recovery from OME in children. PMID- 4040699 TI - Effect of Uristop on primary nocturnal enuresis. A prospective randomized double blind study. AB - Primary nocturnal enuresis (PNE) is a very common problem in pediatric and child psychiatric practice. Many treatments have been tried, but none has proved entirely successful. Uristop, a commercially available alarm device based on a theory somewhat different from those used in the common alarm devices, was tried in a prospective randomized double-blind study. Of 134 enuretic children who were examined on an out-patient ward, 53 were selected for inclusion in this study on the basis of certain criteria. The children were randomized either in a treatment group with a functioning device, or in a control group with a non-functioning device. They used their devices for 6 weeks and were followed for an additional 12 weeks. The sex, age, history of previous urinary tract infection (UTI) or treatment of PNE and a family history of PNE were compared between the groups and no statistical differences were found. In the control group, however, there was significantly more often a history of upsetting life events and previous child psychiatric contact. This difference was not considered as having any effect on the results. The results showed that the device had no effect on the study group as compared with the control group. However, both groups improved significantly as compared with the expected sponaneous cessation of bedwetting. PMID- 4040700 TI - [Effects of hematoporphyrin derivatives--photoirradiation on DNA and RNA synthesis in L1210 cells]. PMID- 4040698 TI - Serum growth-promoting activity in human newborns. Relationship of thymidine activity with birth weight and the length of gestation. AB - Thymidine Activity (TA) was measured by the effect of serum upon incorporation of 3H-thymidine into human lectin-activated lymphocytes in 54 newborns: 32 full term, 11 pre-term and 11 with intra-uterine growth retardation (IGR). Capillary blood was collected at 0-6 hours, with routine samplings. TA values were lower in preterm (0.476 +/- 0.079 U/ml) than in IGR (0.910 +/- 0.118 U/ml, p less than 0.01) and in full-term neonates (1.237 +/- 0.60, p less than 0.001), and also in IGR newborns than in newborns of normal weight (p less than 0.025). In preterm neonates TA was significantly correlated with gestational age (r = 0.715, p less than 0.02), but no such correlation existed in IRG and full-term neonates. When TA values were plotted against birth weight, a correlation was found in preterm (r = 0.715, p less than 0.02) and in IGR newborns (r = 0.714, p less than 0.02), but not in full-term neonates. Longitudinal study up to 21 days did not show significant changes in full-term newborns, while in preterm and IGR neonates TA increased progressively to reach normal values at the 21st day. The correlations observed in newborns between TA, birth weight and gestational age, and the postnatal normalization in newborns with low birth weight, show that TA directly reflects the nutritional state of the fetus. PMID- 4040701 TI - [A case of occult testicular tumor]. AB - A 43-year-old male presented with a left supraclavicular mass as well as an upper abdominal mass. Biopsy of the supraclavicular mass revealed seminoma with components of both embryonal carcinoma and choriocarcinoma. Right orchiectomy was performed because physical examination showed that the left testis was normal but the right testis was slightly atrophic. The primary tumor which was approximately 1 cm in diameter was found in the right testis and histological examination revealed seminoma. When germ cell tumor is found in a region other than the gonads, either primary extragonadal germ cell tumor or occult testicular tumor is considered. To differentiate between the two, it is imperative to make careful histological exploration of the testes. PMID- 4040702 TI - Postnatal decline in pyridoxal phosphate and riboflavin. Accentuation by phototherapy. AB - Riboflavin is a cofactor in the conversion of pyridoxine (vitamin B6) to pyridoxal phosphate (PALP), an essential coenzyme in numerous metabolic pathways, including neurotransmitter synthesis. Riboflavin and pyridoxine are light sensitive in vitro, and conflicting results have been reported on the in vivo effects of phototherapy on riboflavin. We studied 25 full-term neonates receiving phototherapy and 16 healthy controls to evaluate their riboflavin and PALP status. Both vitamin cofactors decreased in both sets of infants, but significantly more so in the irradiated group. While the biologic or clinical importance of a modest biochemical decline in the level of PALP has not been established, it is possible that transient behavioral changes in irradiated, jaundiced neonates could be mediated by decreased availability of PALP. The mechanism for the postnatal decline and the desirability of routine supplementation with pyridoxine, especially in irradiated infants, require further study. PMID- 4040703 TI - Anencephaly in one monoamniotic-monochorionic twin and encephalocele in the other. AB - This is a report of monoamniotic-monochorionic (ie, probably MZ) twins, one of which had anencephaly, whereas the co-twin died of complications of prematurity. Autopsy in this seemingly nonmalformed twin showed a small encephalocele. The literature on MZ twins with discordant anencephaly is often contradictory. It is suggested that this might be due to the difficulty of determining zygosity on the one hand and identifying discordance or concordance on the other. This case is presented as an example of this difficulty; it is discordant with respect to anencephaly, but concordant in the sense of "dysraphic" disturbances. PMID- 4040704 TI - Linear skin atrophy, scarring alopecia, anonychia, and tongue lesion: a "new" syndrome? AB - One of a pair of female monozygotic twins showed skin atrophy with linear alternation of depressed scarlike areas and intervening ridges of normal or nearly normal skin. She was born with friable skin and a vesicular-bullous eruption which was followed by gradual scabbing. Hypohidrosis in the affected areas, heat intolerance, and febrile convulsions were noted in infancy and childhood. No new skin lesions developed, and the existing ones, the sweating disturbance, and the heat intolerance gradually improved with time. Scarring alopecia, congenital absence of three toenails, and a scarlike lesion of the tongue were also present. Their absence in the other twin supports the view that 1) these manifestations all are part of the same syndrome, and 2) this syndrome is nongenetic. Histologically, there were no diagnostic or consistent findings, but the number of skin appendages was diminished, and the elastic fibers were reduced in number and size in one biopsy. The calculated probability for the twins being monozygotic was 0.9998. This family was also remarkable for the presence of alopecia areata in three successive generations with only one instance of apparent nonpenetrance. We conclude that this may represent a previously undescribed syndrome of congenital fragility of connective tissue which predisposed to damage of the elastica, possibly caused by an early inflammatory phase. PMID- 4040705 TI - A premutation that generates a defect at crossing over explains the inheritance of fragile X mental retardation. AB - The view that the Martin-Bell syndrome (X-linked mental retardation with fragile site at Xq27/8) is inherited in a regular X-linked fashion is becoming untenable with the increasing number of reports of transmission through phenotypically normal males. Analysis of the published pedigrees containing such males shows that their heterozygous daughters are never mentally retarded, and have either no fragile site or very few indeed. By contrast, in the next generation, a third of the female heterozygotes are mentally subnormal with an average of 29% fragile sites. These data suggest a premutation that generates the definitive mutation only when transmitted by a female. We propose an inherited sub-microscopic chromosome rearrangement involving the Xq27/8 region that causes no ill effect per se, but generates a significant genetic imbalance when involved in a recombination event with the other X chromosome. This hypothesis explains many of the puzzling genetic aspects of the Martin-Bell syndrome, but it also complicates the interpretation of linkage analysis with genetic markers. PMID- 4040706 TI - Second-look laparotomy after chemotherapy in the management of ovarian malignancy. AB - Eighty-eight patients with ovarian malignancy underwent second-look laparotomy as part of their plan of management at Indiana University Hospital. Thirty-five patients (39.8%) were found to have no gross or microscopic evidence of persistent neoplasm, and an additional 16 (18.2%) had only microscopic tumor. Patients with initial Stage III or IV disease were less likely to have negative findings at laparotomy than were patients with Stage I or II disease. A complete initial cytoreductive operation (residual disease = 0 cm) correlated positively with negative findings at laparotomy. Endometrioid histologic findings were associated with a favorable condition at the second look, but tumor grade was associated with superior survival only for patients with grade 0 disease. Eight of 30 patients (26.7%) with invasive carcinoma and negative findings at second look laparotomy have had tumor recurrence (2 to 63 months), and five of eight have died. Intraperitoneal chromic phosphorus salvage therapy for patients with microscopic disease was promising, with eight of 15 treated patients (53.3%) alive after therapy, with no evidence of disease from 16 to 56 months after the second look. Second-look laparotomy has been the major determinant of continued or alternative therapy for patients with ovarian malignancy. Second-look laparotomy has been incorporated into the standard management plan without a formal clinical trial. The need for a second look may be reduced by identifying patients who do not benefit from the procedure. Patients with persistent disease confirmed by noninvasive means can continue therapy without laparotomy. There is also a subgroup of patients with a favorable prognosis whose therapy could be safely discontinued without laparotomy. PMID- 4040708 TI - International symposium on vulvovaginal mycoses. June 1-3, 1984, Fort Lauderdale, Florida. PMID- 4040707 TI - Long-term risk of menstrual disturbances after tubal sterilization. AB - We analyzed data from the Walnut Creek Contraceptive Drug Study to compare the menstrual characteristics of 719 women who had tubal sterilizations and 1083 women whose partners had undergone a vasectomy. Study participants were enrolled from 1968 to 1972 and followed up through 1976. The tubal sterilization group had slightly increased, though in most instances not statistically significant, risks of moderate to severe menstrual cramps and adverse menstrual bleeding. At follow up intervals longer than 2 years, the tubal sterilization group had significantly increased risks of abnormal menstrual cycles and combinations of two or more adverse menstrual outcomes. Tubal sterilization was not associated with an increased risk of premenstrual symptoms. These findings suggest that the types of tubal sterilization procedures which were performed during the early 1970s possibly carry some increased risk of menstrual disturbances, particularly abnormal cycles, and that it may take more than 2 years for the increased risk to become apparent. PMID- 4040710 TI - Incisions of the pregnant uterus and delivery of low-birth weight infants. AB - This paper calls attention to rapidly increased use of vertical uterine incision and future consequences: impaired uterus, uterine rupture, and iatrogenic premature delivery. In addition, by making a vertical uterine incision we are not gaining much in the size of uterine entrance since the size of the vertical uterine incision is determined by uterine tonus. Most often the uterus is opened by tearing the lower uterine segment transversely with the fingers. Unfortunately this creates the smallest entrance to the uterus because of the uterine structure, shape, and elasticity and could lead to parametrial vein and uterine vessel injury. An alternative to this type of incision is the durable upward curved transverse incision over the supportive lower uterine segment. This technique gives us the biggest entrance to the uterus, without serious side effects, and ensures safe future pregnancies. PMID- 4040709 TI - Repeated candidiasis: reinfection or recrudescence? A review. AB - Candida vulvovaginitis is one of the most common infections encountered by obstetricians and gynecologists from all parts of the world. The modern treatment of vaginal candidiasis with imidazole antimycotics such as clotrimazole has been shown to be highly effective. However, there is a small group of women who experience repeated episodes of vaginal candidiasis. This article reviews possible predisposing factors related to recurrent vaginal candidiasis. PMID- 4040711 TI - The repeatable artifact--a reality of science. PMID- 4040712 TI - Solomon's mothers: a special case of pathological bereavement. AB - Giving up a child for adoption presents a serious emotional and psychological challenge for the mother. Using the components of normal grieving, this paper illustrates the ways in which the bereavement process was distorted and delayed in 22 women seen in psychotherapy who had earlier given up a child. Recommendations are offered for facilitating a healthy mourning process in the relinquishing mother. PMID- 4040713 TI - Gender and symptom sensitivity: report on a Philippine study. AB - Various adverse body states were designated as most frequent symptoms of illness a significantly greater number of times by female university students in the Philippines than by male students responding to a questionnaire. These findings, consistent with greater utilization of medical practitioners by Filipino women than men, are linked to socialization for women's roles. PMID- 4040714 TI - Diurnal changes in thermoregulatory behavior in rats with medial preoptic lesions. AB - Rats with medial preoptic area (MPOA) damage lack adequate autonomic thermoregulatory reflexes but can behaviorally regulate their body temperatures (Tb) in the cold and heat. We examined the performance of such rats on 90-min behavioral thermoregulatory tests. Tests were conducted during the day and night to determine the preferred Tb at different phases of the circadian Tb rhythm. The amplitude of this rhythm was exaggerated after electrolytic MPOA lesions; differences of 3-4 degrees C between daily peaks and troughs were seen (from 37 degrees C during day to 40-41 degrees C at night) compared with control variations of only 1.5-2.0 degrees C (from 36.0-36.5 degrees C during day to 38 degrees C at night). When escaping cold during the day or night or when escaping heat at night, both MPOA-damaged and control rats maintained Tb within +/- 0.5 degrees C of initial values. When escaping heat during the day, control and MPOA damaged rats allowed their TbS at the end of the 90-min behavioral tests to rise to normal night levels (38 degrees C for controls and 40-41 degrees C for MPOA rats). These results demonstrate that rats with MPOA damage behaviorally defend the different phases of their exaggerated Tb rhythm in a manner similar to that of controls. Therefore the exaggerated swings in Tb seen in these preparations have an active regulated component and are not simply passive results of an excessive rhythm in heat production or heat conservation. PMID- 4040715 TI - Light effects on circadian timing system of a diurnal primate, the squirrel monkey. AB - We examined light effects on the circadian timing system of the squirrel monkey. A phase-response curve to 1-h pulses of light was constructed for the drinking rhythm of six animals. The phase-response curve was the same type as that exhibited by nocturnal rodents, with phase delays occurring early in the subjective night and phase advances late in the subjective night. The range of entrainment of 10 monkeys to days with 1 h light and x h dark was determined. Five monkeys used to generate the phase-response curve were also used in the range of entrainment determination. For short light-dark cycles the range of entrainment was smaller than that expected, with no monkey entraining to a day length of less than 23.5 h. PMID- 4040716 TI - Nutritional status of men attending a soup kitchen: a pilot study. AB - Nutritional status and socioeconomic characteristics of 49 men attending a soup kitchen in a residential neighborhood of Birmingham, Alabama were determined by interview, anthropometry and laboratory assays. Laboratory or anthropometric evidence of nutrient deficiency was present in 94 per cent of the subjects. Deficiency of ascorbate (63 per cent), folate (35 per cent), and thiamin (29 per cent) was higher in these men than in either patients or presumably healthy adults. Since soup kitchen meals provided insufficient vitamin C and folate, additional sources of these nutrients should be provided. PMID- 4040717 TI - Cryptosporidiosis in Venezuelan children with acute diarrhea. AB - Thirteen of 120 Venezuelan children with acute diarrhea were found to be excreting Cryptosporidium oocysts in their stools. This confirms that Cryptosporidium can infect immunocompetent children, and the relatively high frequency found suggests that this protozoan may be an important cause of diarrhea in Venezuela. PMID- 4040718 TI - The need for research in the community hospital. PMID- 4040719 TI - Adaptation of the dye-binding protein assay to microtiter plates. AB - The dye-binding protein assay has been adapted for use with microtiter plates and a plate reader. The total volume of the assay was reduced to 0.2 ml, with equal volumes of sample and diluted dye reagent being used. Because of the small volume, the assay is conservative of both protein sample and reagent. The use of microtiter plates allows the absorbance of samples to be read using a plate reader, markedly reducing the time needed for evaluating sample absorbances. This assay is quite sensitive, with a limit of less than 0.5 micrograms bovine serum albumin. In addition, the assay has been calibrated with homogeneous nitrate reductase. The response of nitrate reductase in the assay is about 70% of that of the standard protein, bovine serum albumin. The response of several other proteins was evaluated and the differences in response are discussed. PMID- 4040720 TI - Main systolic blood flow patterns in the left and right ventricular outflow tracts determined by Doppler echocardiography. AB - The main blood flow velocity patterns in the LVOT and RVOT were recorded by pulsed Doppler echocardiography in 28 normal healthy cases, in two athletes, and in 85 patients with atrial septal defects, pulmonary regurgitation, tetralogy of Fallot, aortic regurgitation, mitral stenosis, aortic stenosis, mitral regurgitation, hypertrophic cardiomyopathy, ischemic heart disease, and pulmonary hypertension. Blood flow velocities were displayed using a graphic system to form a real time sonogram, using Fast Fourier Transformation. In the normal group, the blood flow velocity was 1.69 KHz in LVOT, and 1.71 KHz in RVOT. In AR and T/F but not MS, there was high blood flow velocity in the LVOT, and the peak of blood flow velocity was shifted to mid-to late systole. In ASD and VSD with a L-R shunt, high blood flow velocity occurred in the RVOT, and the peak velocity shifted to early systole. Pulmonary hypertension occasionally produced a W- or V shaped curve. In normal subjects, a small "a" wave could be detected in the LVOT recording. The "a" wave began at point B on the AML tracer of the M-mode echocardiography, reached maximum velocity at point C, and returned to zero (baseline) at point C'. The "a" wave was coincident with the R wave of the ECG, and with the Ia of the phonocardiogram (PCG). The normal velocity of the "a" wave was 602 Hz, and the a/H ratio was 0.36. In cases of HCM and IHD, the "a" wave velocity and the a/H ratio correlated with the end diastolic pressure and the peak dP/dT. These data suggest that the Doppler blood flow patterns in the LVOT and RVOT can indicate volume overload in the right and left ventricles, and that the "a" wave velocity and a/H ratio can provide new information concerning cardiac performance. PMID- 4040721 TI - Hemodynamic effects of intravenous PGE1 on patients with arterial occlusive disease of the leg. AB - In 42 patients with arterial occlusive disease of the leg, the hemodynamic effects of prostaglandin E1 (PGE1) given intravenously were studied. Blood pressure of the leg and crest time of the pulse wave did not change significantly, while increases in blood flow at the calf and foot, amplitude of the pulse wave, velocity, and skin temperature at the foot and toes were significant. Skin temperature of the calf dropped significantly. The increase in blood flow, velocity, and skin temperature was significantly more dominant in the distal part of the leg than that in the proximal part. In separate observation of individuals, 12 of the 66 legs with arterial occlusive disease (18%) showed a decrease in skin temperature at the toes. The steal phenomenon was observed most frequently in limbs with rest pain, gangrene, or both. PMID- 4040722 TI - Ultrastructure of cellular changes in the replication of the alcelaphine herpesvirus-1 of malignant catarrhal fever. AB - Cell cultures inoculated with 5 different viral isolates from 4 species of ruminants with clinical signs of malignant catarrhal fever (from the San Diego Wild Animal Park) were examined by electron microscopy. Each had the morphology of a herpesvirus (118 to 220 nm) and was icosahedral, and the nucleocapsid matured in the nucleus of the infected cell. Envelopment of budding occurred with each viral isolate at the nuclear and the plasma membranes. The virions egressed from the cell by budding from the plasma membrane or through channels of the Golgi apparatus or the endoplasmic reticulum. A proposed scheme for the morphogenesis of the herpesvirus of malignant catarrhal fever is presented. PMID- 4040723 TI - Fatal pancarditis in a patient with coexistent Lyme disease and babesiosis. Demonstration of spirochetes in the myocardium. AB - A 66-year-old man developed fever, chills, myalgias, three erythematous skin lesions, and transient left eyelid lag. Because of persistent fever, he was hospitalized 4 weeks after the onset of disease; a peripheral blood smear showed Babesia microti in 3% of his erythrocytes. Eighteen hours later, he died unexpectedly. Autopsy showed pancarditis with a diffuse lymphoplasmacytic infiltrate, and spirochetes were found in the myocardium. Antibody titers to both the Lyme disease spirochete Borrelia burgdorferi and Babesia microti were elevated. The finding of spirochetes in the myocardium and the elevated antibody titers to Borrelia burgdorferi suggest that the patient died from cardiac involvement of Lyme disease. PMID- 4040724 TI - FAB M7: acute megakaryoblastic leukemia--beyond morphology. PMID- 4040725 TI - Ketoconazole and resistant Blastocystis hominis infection. PMID- 4040726 TI - Size of the mastoid air cells and otitis media. AB - Repetitive tympanometric screenings were performed in 79 randomized, otherwise healthy children from 2 to 7 years old. A total of nine screenings, of which three included otomicroscopy, were performed. When the children were 7 years of age, radiographs were made of their mastoid processes in Runstrom's lateral projection. The median size of the cell system was 8.25 cm2. The cell systems were significantly larger (9 cm2) in girls than in boys (7.5 cm2). A significant correlation was found between the size of the cell system and the duration of secretory otitis media; thus, the smallest air cell systems occurred in the children with the longest episodes of secretory otitis, and the largest cell systems in children with no history of secretory otitis. Eardrum changes occurred at the ages of 5, 6, and 7 years in 21%, 32%, and 25% of the children, respectively. Children in whom the same eardrum changes were present at all three examinations had significantly smaller cell systems than those with either no changes or changes only at a few of the examinations. No differences in extent of pneumatization were found, regardless of whether the children had had episodes of acute otitis, had been treated for secretory otitis, or had had neither. In our opinion, this study supports the theory that hypocellularity is a sequela of secretory otitis rather than a cause of the disease. PMID- 4040727 TI - Bacterial and polymorphonuclear leukocyte contribution to middle ear inflammation in chronic otitis media with effusion. AB - Bacteria can be cultured from approximately one third of chronic middle ear effusions, yet the contribution of these bacteria to the pathogenesis of chronic otitis media with effusion (OME) is not clear due to the absence of signs and symptoms of acute infection in most children with this disease. To explore the role of bacteria in chronic OME, lysozyme, lactoferrin, serum complement factors C3 and C5a, and polymorphonuclear leukocyte (PMNL) chemotaxin content was measured in 21 chronic middle ear effusion samples. Concentrations of lysozyme, lactoferrin, and chemotaxin were significantly higher in culture-positive than in sterile effusions. Lysozyme appeared to be contributed by both PMNL and non-PMNL sources in the middle ear space. These non-PMNL sources, presumably middle ear epithelial cells, accounted for 50% to 80% of the lysozyme variation in middle ear effusion. Although C3 and C5a were present in effusion, chemotaxin content correlated poorly with the C3 and C5a content, suggesting that chemotaxins were derived from bacterial peptides rather than from complement activation products. These results suggest that bacteria contribute to chronic middle ear inflammation with effusion. The eradication of bacteria from chronic middle ear effusion might disrupt the host responses which maintain chronic OME. PMID- 4040729 TI - [Prostatic osteocondensing metastases. The value of examining for osteomalacia]. AB - Bone pains observed in patients undergoing estrogen therapy, and presenting with osteoblastic metastases from prostatic cancer are usually related to unsuccessful treatment. In some patients, these pains may result from osteomalacia--ie incomplete mineralization of the new bone--because of the drainage of calcium by the osteoblastic metastases. A clinical, biological and histomorphometric study of bone specimens without decalcification was conducted in ten patients with osteoblastic disease secondary to prostatic carcinoma, who were under estrogen therapy, and for whom a change of therapy was contemplated. The study reports three cases of osteomalacia. Their bone pains were more intense, more diffuse and more permanent than those registered by patients without osteomalacia. All three had had previous fractures of the neck of the femur and a low urinary and serum calcium and phosphorus content. The discovery of osteomalacia by histomorphometric study is important because it allows effective, etiological treatment of the bone pains in these patients. PMID- 4040728 TI - Hydrolase activity in acute otitis media with effusion. AB - Biochemical studies of middle ear effusions (MEE) from patients with chronic or recurrent otitis media with effusion (OME) have demonstrated the presence of significant levels of certain hydrolytic and oxidative enzymes. We have examined MEE from patients with acute OME for the content of a number of lysosomal hydrolases and find no significant differences in the mean values for acid phosphatase, alpha-mannosidase, beta-galactosidase, beta-glucuronidase, hexosaminidase, and neuraminidase between purulent and serous effusions. In every case, the mean activities of these enzymes were greater in culture-positive than in culture-negative effusions although this difference was significant only in the case of neuraminidase. Neuraminidase activity was detected in 78% of those MEEs from which Streptococcus pneumoniae could be cultured and in only 32% to 64% of all other effusions. No correlation was observed between the level of neuraminidase released into the extracellular growth medium and the infectivity of various strains of S pneumoniae. PMID- 4040730 TI - [Systemic cisplatin-based chemotherapy in the treatment of advanced bladder cancer]. AB - Twenty one patients with advanced bladder cancer (metastases and/or loco-regional recurrences) were treated by cisplatin-based chemotherapy (cisplatin, adriamycin, cyclo-phosphamide (8 patients), cisplatin, methotrexate (8 patients) and cisplatin and radiotherapy (5 patients). The results with pure chemotherapy were, on the whole, disappointing, with a remission rate of 25% and a response rate of 50%. Only the combination of cisplatin-based chemotherapy and radiotherapy gave spectacular results with 50% complete response, but even then at the price of a high morbidity rate. PMID- 4040731 TI - Amnesia in monkeys after lesions of the mediodorsal nucleus of the thalamus. AB - Recent successes in developing an animal model of human amnesia in the monkey have made it feasible to try to identify with certainty the specific structures in the diencephalon and medial temporal region that cause amnesia when damaged. Monkeys with small lesions restricted largely to the posterior portion of the mediodorsal nucleus of the thalamus were given a test of memory sensitive to human amnesia and a second test that is analogous to the skill-based tasks performed normally by amnesic patients. The monkeys exhibited a marked impairment on the first test and performed normally on the second. The results show that circumscribed lesions of the mediodorsal nucleus can cause substantial amnesia. PMID- 4040732 TI - Calmodulin-dependent protein kinase in acini from lactating rat mammary tissue: subcellular locale, characterization, and solubilization. AB - Acini isolated from lactating rat mammary tissue were used as the starting material to determine the subcellular location and characteristics of a calcium and calmodulin-dependent protein kinase. The kinase activity phosphorylated a 53,600-Da endogenous protein, required Mg2+, and was stimulated only by the simultaneous presence of calcium and calmodulin. Fractionation by differential and sucrose gradient centrifugation demonstrated the enzyme activity in acinar homogenates to be largely particulate; yet the activity did not co-fractionate with markers for nuclei, secretory vesicles, endoplasmic reticulum, mitochondria, lysozymes, Golgi or plasma membranes. The addition of dephosphorylated K-casein to these preparations resulted in a calcium and calmodulin-dependent phosphorylation of the exogenous substrate. A combination of differential centrifugation and equilibrium sucrose density gradient centrifugation purified the kinase 15-fold and revealed a density for the kinase activity between 1.33 and 1.27 g/cm3, suggesting that the kinase was associated with a particle composed largely or entirely of protein. Gel chromatography on Sephacryl S-1000 also purified the activity significantly, and provided a molecular weight of approximately 10(6). In both procedures, the enzymatic activity and principal endogenous protein substrate were enriched indicating that the kinase was associated with the 53,600-Da substrate. Sodium dodecyl sulfate-gel electrophoresis of the fractions enriched in kinase activity by either gel exclusion chromatography or equilibrium density gradient centrifugation revealed a discrete set of proteins common to both preparations. These included proteins with molecular weights of approximately 32, 35, 54, 70, 94, 100 and 103 K. The calmodulin-dependent protein kinase of mammary acini may be associated in a large complex with these protein species or may represent a polymer of one or several of the proteins. Despite no apparent association with the common phospholipid membranous organelles, the kinase activity was solubilized by treatment with a mixture of phospholipases C and D. After phospholipase treatment and chromatography on Sephacryl S-1000, calcium and calmodulin-dependent phosphorylation was no longer detectable, indicating separation of enzyme and endogenous substrate. Phospholipase treatment of the kinase preparation may be useful in future studies as a method to solubilize the activity. PMID- 4040733 TI - Ca2+-dependent inhibition of smooth muscle adenylate cyclase activity. AB - We have examined the inhibitory regulation by Ca2+ of the adenylate cyclase activity associated with microsomes isolated from bovine aorta smooth muscle. In the presence of 2 mM MgCl2, Ca2+ (0.8-100 microM) inhibited in a noncompetitive manner activation of the enzyme by GTP, Gpp[NH]p, or forskolin. In all instances the value for half-maximal inhibition was between 2 and 3 microM. In contrast, Ca2+ inhibited the activation by MgCl2 (2-50 mM), alone or in the presence of GTP, in a competitive manner. The inhibition of adenylate cyclase by 10 microM Ca2+ was reversed in the presence of either 5 or 25 microM calmodulin or troponin C. These data show that (i) Ca2+, at concentrations similar to those which activate smooth muscle contraction, inhibits the stimulation of adenylate cyclase by several activators; (ii) Ca2+ and Mg2+ compete for a common site on the smooth muscle adenylate cyclase complex; and (iii) the reversal of Ca2+-dependent inhibition by Ca2+-binding proteins may be produced by chelation of the metal by these proteins. PMID- 4040734 TI - [In vitro chemosensitivity of urological malignancies evaluated by colony-forming assay using soft agar]. AB - Over the past year, we have attempted to grow 132 different human tumor samples (78 from urological and 54 from non urological tumors) using a soft agar colony formation assay similar to that originally described by Salmon and colleagues. Formation of colonies in vitro occurred in 44 of 78 primary urological tumors (56%), including 63% (12/19) of renal cancers, 61% (25/41) of uroepithelial cancers and 42% (5/12) of testicular cancers. The effects of in vitro chemosensitivity were analysed using the inhibition of colony growth (more than 70%) at two different cut-off doses which were equilibrated with the achievable AUC doses for the higher cut-off point and to one-tenth of AUC for the lower cut off point. Five of 13 (38%) drugs showed an effective rate between 10% and 38% for the lower cut-off point in vitro. On the other hand, eleven of 13 (85%) drugs. Showed an effective rate between 20% and 67% for the higher cut-off point in vitro. In the tested uroepithelial cancers, none of seven for the lower cut off and three of seven for the higher cut-off were demonstrated to be sensitive cases from the dose corresponding colony inhibition curve for cisplatinum. Nine of the renal cancers were demonstrated for the dose corresponding colony inhibition curve for Interferon. To predict clinical correlation, 16 patients (20 drugs) were treated with identical drugs which were estimated from in vitro chemosensitivity testing. The predictability results were 75%-100% true positive and 85%-100% true negative, with 87% overall predictability. This assay can therefore be used to study differences of biological character including drug sensitivity. PMID- 4040735 TI - [The significance of reinduction chemotherapy with adriamycin for relapsed non Hodgkin's lymphoma of Waldeyer's ring]. AB - Of those patients with localized (CS I-II) non-Hodgkin's lymphoma of Waldeyer's ring who were treated with radiotherapy or radiotherapy plus chemotherapy and who suffered relapses at the National Cancer Center Hospital over the past 22 years, 24 cases were analyzed on the basis of their response rate and duration of remission with reinduction chemotherapy, and survival time after recurrence. The group [ADM (+)], treated with regimens including adriamycin, was compared with the group [ADM (-)] treated with regimens excluding adriamycin. Complete response was seen in 9 out of 11 cases (81.8%) and in 8 out of 13 cases (61.5%) for the ADM (+) group and the ADM (-) group, respectively (p greater than 0.1). The period of complete response of the ADM (+) and ADM (-) groups was compared using the logrank method. The prognosis of the former was significantly (p less than 0.01) better than that of the latter and the median duration of remission was 30 months and 7 months, respectively. When the survival after recurrence of the ADM (+) and ADM (-) groups was compared, the median survival time was 38 months for the ADM (+) group and 12 months for the ADM (-) group, but no significant difference was observed between the two groups (0.05 less than p less than 0.1). PMID- 4040736 TI - [Intra-aortic PGE1 infusion combined with anti-malignant chemotherapy in the treatment of advanced neuroblastoma]. AB - Neuroblastoma is one of the malignant childhood tumors which have a dismal prognosis, but is known to occasionally mature into benign histology spontaneously. Two cases with either stage III or IV neuroblastoma, whose tumors had not been extirpated at the initial operation, were treated by intra-aortic PGE1 infusion combined with oral papaverine and conventional anti-malignant chemotherapy. This therapeutic modality was effective in one case, where the tumor decreased in size and was removed in a second exploratory operation. The histology of the extirpated tumor was benign ganglioneuroma. In this case, however, distant bone metastases were found after the second operation. The role of PGE1 in the mechanism of bone metastasis remains to be determined. PMID- 4040737 TI - Cryptosporidium and diarrhoea. PMID- 4040738 TI - Opioid agonist and antagonist properties of diastereoisomeric N tetrahydronoroxymorphones in mice. AB - Opioid agonist and antagonist properties of diastereoisomeric N Tetrahydrofurfurylnoroxymorphones, Mr 2096 and Mr 2097 were examined in mice using the hot plate and tail flick tests and on acute dependence. Subcutaneous administrations of Mr 2096, the agonist diastereoisomer and Mr 2097, the antagonist diastereoisomer respectively produced analgesia and hyperalgesia in these tests, confirming the involvement of stereoselective opioid receptors in the regulation of thermonociception. Intracerebroventricular injection of Mr 2096 prolonged the tail flick latency, but that of Mr 2097 was without effect. The analgesic effect of Mr 2096 might be due to mimicking the descending inhibition of nociception and suppression of nociceptive reflexes at the level of spinal cord. The absence of hyperalgesia in the tail flick test following the central administration of Mr 2097 might arise from a rapid fall in concentration at relevant receptor sites and/or absence of a significant effect on the spinal reflex. In mice acutely dependent on morphine, Mr 2096 did not precipitate withdrawal. Mr 2097 behaved as an antagonist, precipitating withdrawal. These experiments indicate that stereoselective opioid receptors are involved in acute withdrawal syndrome. This study further confirms the importance of the steric properties of N-substituted moieties in Tetrahydrofurfurylnoroxymorphones. PMID- 4040739 TI - Influence of an inhibition of thromboxane synthetase by imidazole on kidney function in rats during postnatal development. AB - Imidazole, an inhibitor of thromboxane synthetase, reduced the renal excretion of sodium in saline loaded rats. Urine volume was also reduced, whereas the renal excretion of potassium and osmotically active substances was less influenced following imidazole administration. There was also a distinct effect of imidazole (0.5, 5, 10 mg/100 g b.wt. i.p., respectively) on renal excretion of p aminohippurate. These effects are demonstrable if the urine collecting period begins 10 or 60 min after imidazole administration, but not after a longer time interval (120 min). Both renal excretion of sodium and p-aminohippurate were more diminished in adult rats compared with young animals. The renal effects observed following administration of an inhibitor of thromboxane synthetase are quite similar to effects of the cyclooxygenase inhibitors indomethacin and naproxen. PMID- 4040740 TI - Ketoconazole-induced increase in estradiol-testosterone ratio. Probable explanation for gynecomastia. AB - Ketoconazole, an antifungal drug, causes gynecomastia in some patients. It also inhibits androgen and glucocorticoid synthesis. In four volunteer male subjects, 600-mg doses of ketoconazole depressed serum testosterone concentrations markedly, but serum estradiol to a much lesser degree. The bound and free percentages of both hormones were not significantly altered. The net result was a significant elevation of the estradiol-testosterone ratio, expressed as either total circulating hormone or free hormone. In five male patients receiving long term high-dose ketoconazole therapy, the testosterone concentrations fell, but the effect on estradiol was variable. In these patients the estradiol testosterone ratio was persistently increased. Since gynecomastia appears to be the result of an elevated estradiol-testosterone ratio, the selective hormonal effect demonstrated may explain the side effect of gynecomastia after ketoconazole therapy. PMID- 4040741 TI - [Age and changes in the structure of the walls of the intrinsic arteries of the uterus]. AB - By means of common histological, histochemical and morphometrical methods age changes in the cushion-like intimal protrusions of the intraorganic arteries have been studied in 176 uteri of women at all ages that died from trauma and other diseases which do not produce any changes in the uterus. Beginning from two years of age, in the uterus segmentary artery wall certain intimal thickenings are revealed; at this age they consist of immature fibrillar and cellular elements of the connective tissue and single myocytes. At the pubertal age an intensive development of the cushion-like protrusions is observed. The amount of myocytes in them increases at the expense of migration from muscular tunic of the vessel; they arrange chaotically. Then the structure of the elastic and collagenous carcass of the protrusions becomes more complex, the myocytes in them are oriented along the course of the artery, or along the sloping spiral. During adolescence and mature age, cyclic changes in the wall structure of the uterus intraorganic arteries are observed, depending on the phase of the menstrual cycle. During the second part of the proliferative phase, certain retruction of the protrusions is observed, and at the end of the secretion phase--maximal increase in their height. The intimal protrusions are specialized structures, playing an important role in ensuring an optimal blood circulation in the uterus during ovulation and in performing menstruation. Reverse development of these structures takes place in elderly and old age. PMID- 4040742 TI - Panfunduscope lens for laser photocoagulation in gas-filled pseudophakic or aphakic eyes. PMID- 4040743 TI - Serous retinal detachments in thrombotic thrombocytopenic purpura. AB - Serous retinal detachments are a rare ocular complication of thrombotic thrombocytopenic purpura (TTP), with only six previous case reports in the literature. We have recently observed two patients with relapsing TTP who developed bilateral serous retinal detachments during acute exacerbations of their disease. In contrast to all but one of the previously described patients, both of our patients survived the episode during which retinal detachments occurred. Hypertension appears to contribute to the development of retinal detachments in TTP, and vigorous efforts at blood pressure control are indicated. Serous retinal detachments may be a more frequent component of chronic relapsing TTP than has been suspected. PMID- 4040744 TI - The role of allergy in the pathogenesis of otitis media with effusion. AB - To explain an allergic basis for the development of otitis media with effusion (OME), it was suggested that the middle ear mucosa can act as an allergic "shock organ." To evaluate this possibility, 16 juvenile rhesus monkeys were passively sensitized to pollen by intravenous injection of allergic human serum. All ears were then challenged by insufflation of pollen via the nose and eustachian tube (ET), twice daily, for four to five days. Daily tympanometry and otomicroscopy were performed, and on the last day of challenge, tympanocentesis was done to recover effusions. Five animals were killed and the middle ears were processed for histologic study. The results showed that none of the ears developed a middle ear effusion or OME. It is concluded that middle ear challenge with an appropriate pollen antigen in passively sensitized rhesus monkeys does not initiate an inflammatory reaction in the middle ear or induce OME. PMID- 4040745 TI - Successful in vitro growth of human head and neck cancer after transplantation in nude mice. AB - Head and neck tumours from 14 different lines growing in athymic nude mice were cultured in a soft agar cloning assay. Eleven lines (79%) demonstrated growth with more than 100 colonies per 3 X 10(5) cells plated. These results are much more favourable than those obtained with head and neck tumours taken directly from the patient. It is suggested that the combination of the athymic nude mouse xenograft model with the clonogenic assay could serve as a new screening model for chemotherapeutic agents against head and neck cancer. PMID- 4040746 TI - Evaluation of paste formulations of fenbendazole plus piperazine against benzimidazole-resistant cyathostomes in horses. PMID- 4040747 TI - Stress and accidents. AB - Three types of stress are described: environmental stress, acute reactive stress, and domestic or life stress. Each of these is discussed and the evidence relating the stress to accidents is evaluated. This evidence is drawn from laboratory experiments, surveys, and accident and incident reports. It is concluded that there is good reason to link some forms of stress with accidents; possible ameliorative measures are suggested. PMID- 4040748 TI - Fitting heredity-environment models jointly to twin and adoption data from the California Psychological Inventory. PMID- 4040749 TI - [The dynamics of behavioral changes in mice induced by social isolation]. AB - Various behavioural patterns such as spontaneous locomotion, open-field behaviour and aggressivity undergo typical changes in socially isolated mice. Each of them shows a specific course depending on the duration of isolation. Differences in time courses and quantitative changes demonstrate that not only a general mechanism such as decreased arousal threshold is responsible for the complex alterations. It seems that many different mechanisms in the CNS underly the isolation syndrome, but the functional connections between the different alterations are unknown. PMID- 4040750 TI - Synergism of vitamins A and C on fibrinolysis. AB - A hitherto unknown synergism exerted by retinol (vitamin A) and L-ascorbic acid (vitamin C) was discovered using endothelial cells. Retinol stimulated the extracellular and intracellular activities of plasminogen activator up to approximately 8- and 4-fold from the control values, respectively. L-Ascorbic acid enhanced the extracellular and intracellular activities up to approximately 1.5-fold. Above all it was demonstrated that their effects on extracellular activity were synergistic; simultaneous administration of these two vitamins enhanced the extracellular activity up to a 20- to 50-fold. Synthesis of plasminogen activator induced with vitamins A and C was inhibited by a protein synthesis inhibitor, cycloheximide. PMID- 4040751 TI - The influence of a new compound, PATP, on glucose transport in the isolated fat cell. AB - A newly synthesized compound, N-(4-pyridylcarbonyl amino) 1, 2, 3, 6 tetrahydropyridine (PATP) was earlier found to elevate the blood glucose level in rats. This suggested that the compound might be accomplishing this by blocking glucose transport into tissue cells. This hypothesis has now been examined in the isolated fat cell system using a modification of the method to improve the accuracy of measurements made. This study indicated that PATP is a competitive inhibitor of glucose transport and metabolism (KI = 0.89 mM) but could not unequivocally prove that the effect was on transporter action alone. That the compounds action was at this level, however was shown by its ability to inhibit the uptake of the transported but non-metabolized sugar, 3-0-methyl glucose (KI = 3 mM). PATP is a nonphenolic inhibitor of glucose transport unrelated in structure to the sugar or to another more potent inhibitor, phloretin. PMID- 4040752 TI - A role for somatomedin C as a differentiating hormone and amplifier of hormone action on ovarian cells: studies with synthetically pure human somatomedin C and swine granulosa cells. AB - Isolated swine granulosa cells incubated in chemically defined medium in vitro responded to synthetically pure human somatomedin C/IGF-I in a dose and time dependent fashion with increased pregnenolone, progesterone and estradiol biosynthesis. These stimulatory actions were not mimicked by growth hormone, proinsulin, desoctapeptide insulin, epidermal growth factor, or fibroblast growth factor. Moreover, somatomedin C/IGF-I augmented the steroidogenic response of granulosa cells to exogenously supplied sterol substrate in the form of low density lipoprotein, and amplified the stimulatory actions of the classical ovarian effector hormones, estradiol and follicle-stimulating hormone, in a synergistic fashion. The ability of somatomedin C/IGF-I to stimulate estradiol production on the one hand, and to act synergistically with estradiol to stimulate progesterone biosynthesis on the other hand, suggests a unique intrafollicular mechanism for amplifying progestin biosynthetic capacity in granulosa cells. PMID- 4040753 TI - Microinjection of macromolecules into leukemic cells by cell fusion technique: search for intracellular growth-suppressive factors. AB - To investigate the intracellular molecular events during leukemic cell proliferation, we have examined the method of ghost-mediated microinjection of macromolecules into leukemic cell line cells (HL-60). Samples were packed into red cell ghosts. Microinjection was performed by the fusion of ghosts and HL-60 cells using the hemagglutinating virus of Japan (HVJ). Fusion rate was about 80 90%, when determined by the injection of FITC-labeled globulins (IgG) or diphtheria toxin fragment A into HL-60 cells. When the nuclear protein extract from normal granulocytes was injected into HL-60 cells, their growth was significantly suppressed. The injection of the nuclear protein extract from HL-60 itself into HL-60 cells did not inhibit their growth. This finding suggests that leukemic cells may be deficient in intracellular regulatory factors which have suppressive activity on cell growth. PMID- 4040754 TI - Regional linkage analysis of the dioxin-inducible P-450 gene family on mouse chromosome 9. AB - The dioxin-inducible P-450 gene family in the C57BL/6N mouse comprises two genes, P1-450 and P3-450. Restriction endonuclease-digested genomic DNA was probed with P1-450 and P3-450 full-length cDNA clones in an attempt to find species-specific fragment length differences between mouse and hamster cell lines and any restriction fragment length polymorphism among four inbred mouse strains. With this Southern blot hybridization technique, PstI fragments were used to distinguish between the mouse and hamster P1-450/P3-450 genes, and PvuII fragments were used to distinguish P3-450 differences between the AKR/J and C57L/J inbred strains. Analysis of nineteen mouse X hamster somatic cell hybrid lines and sixteen AKXL (AKR/J X C57L/J) recombinant inbred lines showed that the P1-450/P3-450 genes are located near the Mpi-1 locus, between the Thy-1 and Pk-3 loci, in the middle portion of mouse chromosome 9. PMID- 4040755 TI - Specific binding of concanavalin A to free inositol and liposomes containing phosphatidylinositol. AB - We previously reported that concanavalin A could bind specifically to liposomes containing phospholipids and lacking glycoconjugates (Biochem. Biophys. Res. Comm. 74, 208, 1977). In the present study we show that the binding of concanavalin A to the liposomes was greatly increased (up to 5 fold) by the presence of phosphatidylinositol in the liposomes. Furthermore, the binding of concanavalin A to phosphatidylinositol-liposomes was specific and could be inhibited by either alpha-methyl mannoside or by myo-inositol. We also found that concanavalin A-induced lymphocyte mitogenesis could be inhibited either by alpha methyl mannoside or by myo-inositol. Simultaneous addition of both inhibitors to concanavalin A and liposomes showed that inhibition was non-competitive: alpha methyl mannoside was more inhibitory to liposomes lacking phosphatidylinositol, and myo-inositol was more inhibitory to liposomes containing phosphatidylinositol. This suggests that the binding site for inositol might be different than that for mannose. Equilibrium dialysis and Scatchard plots revealed 4 binding sites each for inositol and mannose at neutral pH. The binding constants of concanavalin A were 0.13 X 10(4) and 0.25 X 10(4) liters/mole respectively for inositol and mannose. We conclude that concanavalin A binds specifically to the inositol portion of phosphatidylinositol. PMID- 4040757 TI - The PDC-109 protein from bovine seminal plasma is similar to the gelatin-binding domain of bovine fibronectin and a kringle domain of human tissue-type plasminogen activator. AB - PDC-109, a protein of unknown function, is a major component of bovine seminal plasma. Using a computer program designed to detect evolutionary relationships between proteins, I find that the PDC-109 protein is similar to the gelatin binding domain of bovine fibronectin and part of a kringle domain of human tissue type plasminogen activator (t-PA). The computer-based comparison of the amino acid sequence of PDC-109 with that of the gelatin-binding domain of fibronectin and part of the second kringle domain of t-PA yields scores that are 15.5 standard deviations and 7.8 standard deviations higher, respectively, than were obtained with a comparison of randomized sequences of these proteins. The probability (p) of getting these scores by chance is less than 10(-50) and 3 X 10(-15), respectively. The similarity between the amino acid sequences of PDC-109 and the gelatin-binding domain in fibronectin and the kringle of t-PA suggests some approaches for identifying the functions of PDC-109. Both t-PA and the gelatin-binding domain of fibronectin have adhesive functions, and the gelatin binding domain promotes viral transformation of fibroblasts in culture. These functions may be associated with the PDC-109 protein. PMID- 4040756 TI - Binding of cis-dichlorodiammine platinum(II) to metallothionein in Ehrlich cells. AB - The antitumor agent, cis-dichlorodiammine Pt(II), is cytotoxic to Ehrlich cells in culture. These cells contain a substantial amount of metallothionein in the absence of inducers of the protein. At concentrations of drug which cause 60% inhibition of cell proliferation, most of the platinum is found in the cytosol. Of this about 30% is bound in the metallothionein fraction. Isolated rat liver metallothionein reacts slowly with hydrolyzed cis-dichlorodiammine Pt(II). Thus, metallothionein is a major cellular site of binding of the platinum complex at concentrations which inhibit tumor growth. PMID- 4040758 TI - A Z-DNA binding protein isolated from D. radiodurans. AB - A DNA binding protein isolated from D. radiodurans changes CD-spectrum of Z-form poly(dG-dC) X poly(dG-dC). We have found that a positive band at 268 nm is converted close to that of B-form in the presence of the protein. Concomitantly, a negative band at 295 nm shown by Z-form poly(dG-dC) X poly (dG-dC) was weakened by the protein but not by albumin. Such changes in the CD-spectra were not induced by the protein and by albumin when they were mixed with Z- or B-form poly(dG-me5dC) X poly(dG-me5dC) or with B-form poly(dG-dC) X poly(dG-dC). The protein formed a complex preferentially with Z-form poly(dG-dC) X poly(dG-dC). PMID- 4040759 TI - Anticytoskeletal autoantibodies in the connective tissue diseases. AB - The sera of 103 patients with connective tissue diseases were studied for the presence of anticytoskeletal antibodies by using an indirect immunofluorescence method. PTK2 cells fixed with paraformaldehyde and digitonin were used as substrate. Antibodies to intermediate filaments were detected in sera of 85.7% of polymyositis/dermatomyositis (PM/DM), 62.8% of systemic sclerosis, 54.5% of rheumatoid arthritis, and 37.5% of systemic lupus erythematosus patients, and in 42.5% of normal sera. High titers of these antibodies, which were IgM, were present in 30% of patients' and 5% of normal sera. Antibodies to microfilaments were present in 11.6% of patients' sera and absent in all control sera. These antibodies were IgM or IgG. The switch from an IgM to an IgG antibody was observed in 1 patient. An IgG antibody to the spindle poles and midbody of mitotic cells was present in the serum of 1 patient with the CREST syndrome (calcinosis, Raynaud's phenomenon, esophageal dysmotility, sclerodactyly, telangiectasias). Antibodies to intermediate filaments and to microfilaments occur commonly in the connective tissue diseases, particularly in PM/DM, and are not detected with substrates or fixation methods used in routine antinuclear antibody testing. PMID- 4040760 TI - Otitis media: the role of speech-language pathologists. PMID- 4040761 TI - The amygdala and forced immobilization of rats. AB - Forced immobilization of rats produced changes in the multiple-unit activity in the medial, central and lateral nuclei of the amygdala. Chlordiazepoxide suppressed the activity of these units. Low-level electrical stimulation of the area of these units produced gastric erosions only when the stimulation was applied to the central amygdalar nucleus. It was concluded that these areas of the amygdala respond to the emotional component of immobilization stress. PMID- 4040762 TI - Cyclophosphamide in the male rat: behavioral effects in the adult offspring. AB - Cyclophosphamide in a daily dose of 10 mg/kg was injected intraperitoneally in male Wistar rats for 15 days. Two rats each time were killed for testis examination at regular intervals within 100 days following treatment (over 2 spermatogenetic cycles). One hundred days after the end of the treatment, the other rats, whose spermatogenesis had recovered in the meantime, were mated with 3-month-old females. Offspring were evaluated in regard to the mean number per litter, sex ratio, frequency of gross external malformations, growth pattern, mortality in the first 4 months of life and reproductive ability at 6 months of age. Offspring behavior was also examined between 10 and 14 weeks of age. They were evaluated for spontaneous activity and emotionality with an open field test and for learning ability with an avoidance conditioning test. Cyclophosphamide induced a significant decrease in the number of primary spermatocytes and spermatozoa. Only learning ability was altered in the offspring from the treated males, for the animals which succeeded in the avoidance conditioning test did not learn as rapidly as the controls. However, the difference was significant only in the males. Behavioral abnormalities and the possible genetic factors involved are related to the particular concept of 'physioteratogenesis'. PMID- 4040763 TI - Human conditioned compensatory response to alcohol cues: initial evidence. AB - Alcohol cues elicited a conditioned autonomic response that was opposite in direction to the effect of alcohol. Normal male social drinkers given placebo following four alcohol conditioning sessions showed a compensatory response consisting of decreased pulse transit time, vasomotor activity, and finger temperature. This pilot research, supports the application of a classical conditioning model to human alcohol problems. PMID- 4040764 TI - Incidence of major congenital malformations in offspring of alcoholics and polydrug abusers. AB - The incidence of major congenital malformations was compared in the offspring of mothers who abused alcohol only (group I), versus mothers who abused alcohol and opiates (group II) during pregnancy. In group I the percent of patients with malformations was 33, where as in group II it was 14. The prevalence of fetal alcohol syndrome was higher in blacks than Hispanics. Independent of race the alcohol-opiate combination seems less teratogenic to the fetus than alcohol alone. PMID- 4040765 TI - Homology between the primary structures of beta-lactoglobulins and human retinol binding protein: evidence for a similar biological function? AB - Two types of beta-lactoglobulins were identified and isolated from horse colostrum: beta-1g I and beta-1g II. The amino-acid sequence of some tryptic peptides from the new monomeric beta-lactoglobulin II was determined and aligned to the other beta-lactoglobulins of known sequence and to the human plasma retinol-binding protein. The comparison of the primary structures of beta lactoglobulins and human retinol-binding protein shows an unexpectedly high homology of 25%. We found 37 identities among 149 possible homologous residues. Among them is a tryptophan residue at position 19 of beta-lg which might represent the binding site of beta-ionone. These data suggest a common origin of beta-lactoglobulin and human retinol-binding protein and imply that beta lactoglobulins may be involved in the metabolism of retinol. PMID- 4040766 TI - The amino-acid sequence of beta-lactoglobulin II from horse colostrum (Equus caballus, Perissodactyla): beta-lactoglobulins are retinol-binding proteins. AB - beta-Lactoglobulin isolated from horse colostrum is heterogeneous and contains two components: beta-lactoglobulin I and beta-lactoglobulin II. These two proteins are monomeric and show differences in their electrophoretic mobilities, chain lengths and primary structures. The complete amino-acid sequence of beta lactoglobulin II was determined by automated Edman degradation of the intact protein and of the peptides derived from these by digestion with trypsin or chymotrypsin and by chemical cleavage with cyanogen bromide. Unlike other beta lactoglobulins which contain 162 amino acids, horse beta-lactoglobulin II is unique in that it contains 166 amino acids. The additional four amino acids represent an insertion between positions 116 and 117 of other beta-lactoglobulins so far sequenced, including horse beta-lactoglobulin I. Sequence comparison of beta-lactoglobulins I and II from horse colostrum reveals 48 amino acid substitutions (30%). Such a diversity between members of the beta-lactoglobulin gene family has not been encountered before. Sequence comparison with bovine beta lactoglobulin A shows 85 amino acid replacements accounting for 53% of the residues. The structural homology with human retinol-binding protein may reveal similar biological functions and clues to the origin of milk proteins. PMID- 4040767 TI - [Lissencephaly in one of twins]. PMID- 4040768 TI - Cytoskeleton rearrangements during calcitonin-induced changes in osteoclast motility in vitro. AB - Although relatively little is known about osteoclastic degradation of bone, observations both in vivo and in tissue culture in vitro suggest that osteoclast motility is required. Osteoclasts with abundant motile activity and responsiveness to a bone-regulating hormone, calcitonin, have recently been isolated from rat femur and maintained in culture for short periods of time. Using indirect immunofluorescence with antibodies to tubulin and myosin and NBD phallacidin staining for F-actin, we have studied cytoskeleton distributions in such osteoclasts, either untreated or treated with calcitonin. Untreated and unresponsive cells were well spread on the substratum and displayed striking motility in time-lapse cinematography. In these cells a fine network of microfilaments but no stress fibers could be seen. Ruffles, both at the cell periphery and on the dorsal cell surface, stained intensely for F-actin. In contrast, myosin staining appeared in a relatively diffuse dotty pattern that diminished toward the cell periphery and was absent from the ruffled borders. Microtubules labeled in a pattern similar to that typically seen in a variety of mononuclear cells with microtubules radiating from the perinuclear region toward the cell periphery. In cells that responded to calcitonin by ceasing motile activity and retracting cytoplasm, microtubules were not detectably altered. Both myosin and actin labeling, however, changed dramatically, with retraction fibers labeled brightly for actin but not for myosin. Early in cytoplasmic retraction, myosin stained most intensely as a ring at the cell periphery at the base of retraction fibers.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4040769 TI - Cystic fluid-platinum kinetics in ovarian cancer patients: relevance to cis dichlorodiammine platinum (II) sensitivity testing in vitro. PMID- 4040770 TI - Platelet-associated complement in chronic ITP. AB - Chronic ITP is due to antibody-induced destruction of platelets by the reticuloendothelial (RE) system. The role of complement in this process is unclear. We measured platelet-associated complement (PAC) components C3, C3bi, C4 and C9 in 16 patients with chronic ITP, in two of these patients prior to and after splenectomy. Competitive solid-phase radioimmunoassays using monoclonal antibody (anti-C3d, anti-C3bi neoantigen or anti-C9) or affinity-purified heterologous antibody (anti-C4) were used. Mean values (+/- SD) of normal subjects (ng/10(7) plts) were: PAC3d 17.6 +/- 6.8; PAC3bi 11.6 +/- 2.3; PAC4 1.6 +/- 0.5; PAC9 9.9 +/- 2.6. Significantly elevated (greater than 2 SD) PAC3, PAC3bi, PAC4 and PAC9 levels occurred in 12/16, 11/14, 10/14 and 5/9 chronic ITP patients. The PAC3, PAC3bi and PAC9 values correlated inversely with the patients' platelet counts (P less than 0.001); PAC4 levels did not. A positive correlation was also noted between PAC3, PAC3bi and PAC9 while PAC4 values showed no correlation. Two patients with preoperative elevation of all four PAC proteins showed normalization of PAC3, PAC3bi and PAC9 values after a splenectomy-induced remission; PAC4 levels remained elevated for up to 5 months after surgery. We conclude that in vivo C activation occurs in most chronic ITP patients with binding of C3 and C9 to the platelet surface. This in vivo C activation may promote more efficient phagocytosis (C3b) and possibly platelet lysis (C5-9) in some ITP patients. PMID- 4040771 TI - Urodynamic and clinical assessment of the Lyodura sling operation for urinary stress incontinence. AB - A Lyodura sling operation for urinary stress incontinence was performed on 36 patients. The success rate was 89%, when success was defined as absence of objective urine loss at coughing or straining, with full bladder in the upright position and during a Urilos test, at least 6 months after surgery. Full urodynamic assessment, including urethral rest and stress profiles, were performed before, and 6 months after, surgery. Success of the operation depended mainly on enhancement of urethral pressure transmission. Functional length of the urethra and maximal urethral pressure did not influence the success rate. The procedure is especially suitable in patients with some degree of uterine or vaginal prolapse. PMID- 4040772 TI - Reconstitution of the glucose transporter from bovine heart. AB - Reconstitution of the glucose transporter from heart should be useful as an assay in its purification and in the study of its regulation. We have prepared plasma membranes from bovine heart which display D-glucose reversible binding of cytochalasin B (33 pmol sites/mg protein; Kd = 0.2 muM). The membrane proteins were reconstituted into liposomes by the freeze-thaw procedure. Reconstituted liposomes showed D-glucose transport activity which was stereospecific, saturable and inhibited by cytochalasin B, phloretin, and mercuric chloride. Compared to membrane proteins reconstituted directly, proteins obtained by dispersal of the membranes with low concentrations of cholate or by cholate solubilization showed 1.2- or 2.3-fold higher specific activities for reconstituted transport, respectively. SDS-polyacrylamide gel electrophoresis followed by electrophoretic protein transfer and labeling with antisera prepared against the human erythrocyte transporter identified a single band of about 45 kDa in membranes from both dog and bovine hearts, a size similar to that reported for a number of other glucose transporters in various animals and tissues. PMID- 4040773 TI - [Role of the oncogene in the mutagenic activity of bovine adenovirus type 3]. AB - The mutagenic and carcinogenic effect of two EcoRI-fragments of bovine adenovirus type 3 (BAV-3) DNA inserted into pBR325 has been studied. The C fragment (located between 3,6 and 19,7 map units) contains the viral oncogene, the C fragment (between 44,3 and 63,7 map units) displays no transforming activity. It has been established that oncogene BAV-3 statistically true increases the yield of mutants resistant to 6-mercaptopurine (6MP) in Chinese hamster cells. The C fragment, pBR325 without viral sequences and DNA fragments of different molecular weights from normal Syrian hamster cells have no mutagenic effect. The control over tumor formation in syngenic mice after injection of C3H10T 1/2 and D. C fragments and pBR325 treatment exposed a parallelism between the mutagenic and transforming effect. The study of the combined effect of viral DNA fragments and the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) which increases the transforming activity of different carcinogens, shows that the promoter increases the frequency of mutants after viral oncogene treatment and does not induce mutagenic activity of those types of DNA which are unable to transform the cells. PMID- 4040774 TI - [Fibrinolytic activity of heart tissues and aorta of rats undergoing electroshock]. AB - In the first minute of shock caused by electric current passing through the rats parietal lobe the increase of fibrinolytic activity of euglobulin fraction of blood occurs. During the investigation of the right heart ventriculus tissue and aorta by histochemical method of Todd in our modification the decrease of fibrinolytic activity in wall of aorta (on 80%) and in tissue of heart ventriculus (on 30%) has been revealed in tentative animals as compared with control ones. It is suggested that the entering of plasminogen activator from vessel wall into the blood flow plays an important role in activation of fibrinolytic system in generalized reaction of organism to strong stress action. PMID- 4040775 TI - [Effect of stress-inducing factors on the behavior of monkeys. I. The behavior of monkeys under acute emotional stress]. AB - The behavior of Papio hamadryas pubertal males under the immobilizational stress conditions has been studied. It has been established that this very type of stress appeared to be a powerful irritant for the individuals of this species and age leading them into the depression state. The process of normalization of behavior after the 2-hour immobilization lasted for about 72 h. The main consequences of the stress were the violation of locomotion, the reception by individuals of unnatural postures, the trembling of limbs and the violation of coordination. The reaction of stress was greatly influenced by the position of individual in the hierarchic system. The dominant (alpha) and the most subdominant (z) males bore the stress easier. The intensification of food activity was marked within the male z. In certain period after the immobilization the tendency of the growth of friendly contacts between the individuals was found. The frequency of aggressive behavior after the stress lowered. The violation of manipulation activity was also marked. These regularities are of great importance for the reconstruction of group social behavior models of protohominid's societies. PMID- 4040776 TI - [Synthesis of sesquiterpene metabolites in a Trichothecium roseum culture]. AB - During the cultivation Trichothecium roseum forms biologically active sesquiterpenes in particular trichothecin and trichothecolon. The quantitative ratio of these compounds in cultural liquid changes depending on the cultivation conditions. The compounds taking part in terpenoids shant specifically increase the synthesis of sesquiterpenes in fungus culture. A possibility of intertransformation of different trichothecenes provides the stability of the fungus-producent to its toxical metabolites. A fermental system carrying out the transformation of trichothecin into trichotecolon has been revealed. PMID- 4040777 TI - Imbalance of hemispheric functions in the major psychoses: a study of handedness in the People's Republic of China. AB - A study of hand preference and eye dominance in schizophrenia, manic-depressive psychosis, and normal controls was carried out in the People's Republic of China. An excess of sinistrality was found in both men and women schizophrenics, but not in manic-depressive patients. Both the manic-depressive and schizophrenic psychoses are characterized by a significant excess of left eye dominance and by an increasing divergence between eye and hand dominance when compared to the controls. The major published studies investigating hand preference in psychopathology are reviewed, and possible interpretations of the conflicting findings are suggested. PMID- 4040778 TI - [Prevention of stress-induced disorders of myocardial contractile function by using sparing adaptation to short-term stress effects]. AB - Adaptation to repeated short-term stress is known to prevent to a considerable extent the depression of the myocardial contractile function which usually develops under long-term stress. But the adaptation itself has a "cost", i. e. it results in limited but significant disturbances of myocardial contractile function. The present review documents the method of adaptation involving few actions with prolonged intervals between them. It has been established that such an adaptation per se does not induce any disturbances of contractile function. At the same time it prevents completely the depression of contractile function caused by stress. PMID- 4040779 TI - [Comparative evaluation of the protective effect of adaptation to short-term stress exposures in damage to the heart and portal vein from long-term stress]. AB - The effect of the preliminary adaptation to short-term stress actions carried out under different conditions was studied in the myocardium and vascular smooth muscle damaged by long-term immobilization stress. The preliminary adaptation performed under "sparing" conditions was shown to protect more effectively the right atrial myocardium and portal vein against damages induced by long-term immobilization than that carried out under stringent conditions. The sparing adaptation allowed avoiding the appearance of the structural "price" of the adaptation, i.e. the depression of myocardial contractile function induced by adaptation itself. PMID- 4040780 TI - [Neurophysiological analysis of the development of endocrine and hypertensive reactions in long-term emotional stress]. AB - A study was made of the effect of chronic emotional stress on the formation of hypertension in animals. This was shown to be related to dynamic changes in the function of the CNS, particularly in the hypothalamic apparatus of the neuroendocrine control. The above changes played a role in the formation of hypertensive vascular reactions accompanied by a high hormonal secretion of the adrenal cortex and thyroid. During stabilization of high arterial blood pressure at the late stages of the "after-effect", the hormonal secretion returns to normal. PMID- 4040781 TI - [Acceleration of the vertical migration of corneal epithelial cells in white rats under chronic immobilization stress]. AB - Autoradiography with 3H-thymidine was employed to study DNA synthesis and the rate of the migration of labeled nuclei from the basal layer to the surface layers of albino rat corneal epithelium after repeated immobilization stress. The studies were performed at once, and 24 and 72 hours after 3H-thymidine injection. Post-stressor activation of DNA synthesis and acceleration of the vertical migration of the cells were recorded. PMID- 4040782 TI - [Pharmacological correction of the disorders of cardiac contractile function in stress]. AB - It has been established that sodium hydroxybutyrate, prolactin, propranolol and ionol are capable of preventing the depression of the contractile function of the heart and of decreasing the glycogen level in the myocardium, provoked by emotional stress. PMID- 4040783 TI - A monoclonal antibody, specific for human fibrinogen, fibrinopeptide A-containing fragments and not reacting with free fibrinopeptide A. AB - Spleen cells of BALB/c mice, immunized with fragments Y of normal human fibrinogen, were fused with P3 X 63 Ag 8653 myeloma cells. A clone was found which produces monoclonal antibodies (Mab-Y18) of the IgM kappa type. Mab-Y18 is immunoreactive with normal human fibrinogen, and its fragments X, Y, N-terminal disulphide knot, A alpha-chain, and A alpha stretch 1-51. The immunoreactivity with these same fragments disappears upon treatment with thrombin or arvin. This strongly suggests that fibrinopeptide A is an essential component of the Mab-Y18 epitope. This is supported by the finding that Mab-Y18 prolongs the thrombin and arvin clotting times of human fibrinogen by inhibition of the fibrinopeptide A release. More detailed information about the nature of the Mab-Y18 epitope was obtained from studies with genetic variants of human fibrinogen (especially fibrinogen Metz) and with fibrinogens from other mammalian species. These studies show that amino acid residue A alpha 16 (arginine) of fibrinopeptide A is essential for the Mab-Y18 epitope. Mab-Y18 does not react with free fibrinopeptide A. PMID- 4040784 TI - Uptake of tri-p-cresyl phosphate in soybean plants. PMID- 4040785 TI - Inhibitory effects of forskolin and papaverine on nerve conduction partially blocked by tetrodotoxin in the frog sciatic nerve. AB - The effects of forskolin, sodium fluoride and papaverine on compound action potentials were investigated in de-sheathed sciatic nerve preparations of the frog. Forskolin decreased in a concentration-dependent manner the amplitude of compound action potentials when nerve conduction was partially blocked by tetrodotoxin (TTX). In the presence of TTX a 50% decrease in the action potential amplitude recorded was obtained with about 2.5 microM forskolin. Sodium fluoride did not modify the amplitude of compound action potentials partially blocked by TTX. Papaverine also decreased the amplitude of compound action potentials partially inhibited by TTX. A 50% decrease in the action potential amplitude recorded in the presence of TTX was obtained with about 10 microM papaverine. The possibility that cyclic AMP modulates axonal excitability by interfering with the entry of sodium through the TTX-sensitive sodium channel is discussed. PMID- 4040786 TI - Surgical correction of post-operative retrograde ejaculation. AB - Retrograde ejaculation is a known complication of bladder neck surgery. Revision of a bilharzial bladder neck obstruction accentuates the incidence of this complication. Some of the difficulties in the surgical correction of retrograde ejaculation are directly related to pathological changes caused by bilharziasis. In this study a new length of premontanal urethra is formed using the trigonal urothelium and the trigonal muscles with their intact sympathetic innervation to correct retrograde ejaculation following bladder neck surgery. Normal (antegrade) ejaculation was restored in four of five men using this procedure. The physiological basis of the procedure is discussed. PMID- 4040787 TI - Survey of antibiotic prophylaxis in British urological practice. AB - Guidelines for the use of prophylactic antibiotics to cover operative procedures on the urinary tract have been suggested, but the extent to which these have been adopted into routine practice has not been assessed. This survey documents the use of prophylactic antibiotics in urological surgery in Britain. It demonstrates that awareness of the potential role of antibiotic prophylaxis is increasing. Most urologists now adopt a selective approach in the use of prophylactic agents. PMID- 4040788 TI - Long term alcohol consumption induces microtubular changes in the adult rat cerebellar cortex. AB - The effects of prolonged alcohol consumption on the microtubules of Purkinje cell dendrites and granule cell axons were studied in adult rats fed alcohol for 1, 3, 6, 12 and 18 months and compared with respective age-matched controls. A significant consequential decrease in the number of dendritic microtubules in alcohol-fed rats was found when compared with the respective controls. Conversely, an increase in the number of these organelles was found in both ascending and parallel portion of the axons in the experimental animals. The possibility of a relationship between microtubular changes and previously reported cerebellar cortex alcohol-induced structural alterations is advanced. PMID- 4040789 TI - Peripheral axotomy induces neurofilament decrease, atrophy, demyelination and degeneration of root and fasciculus gracilis fibers. AB - We have recently shown that peripheral axotomy by hindlimb amputation in adult cats sequentially results in neurofilament and microtubule decrease and axonal atrophy, myelin wrinkling, myelin remodeling (de- and remyelination), more atrophy and axonal degeneration in proximal sciatic and L7 segmental nerve fibers. The neuropathologic, morphometric and teased fiber alterations in the myelinated fibers (MF) of roots and sampled levels of fasciculus gracilis in groups of adult cats 24 months after hindlimb amputation have now been studied. We found: a severe decrease of neurofilaments, axonal atrophy, myelin wrinkling, de- and remyelination and axonal loss in posterior root axons; that these morphologic abnormalities extended up the fasciculus gracilis in the appropriate territories established from degenerative studies; that the retrograde effect was less severe in ventral root fibers, although atrophy and sprouting were demonstrated here, and that the cellular sequence of retrograde atrophic degeneration of ascending axons was similar to that observed in proximal stump axons. These findings confirm that primary afferent neurons are more vulnerable to axotomy than lower motor neurons and may provide an additional explanation for the poorer functional restoration of sensory than of motor deficit after root compression and in delayed nerve reconnection. Our observations also have important implications for interpretation of neuropathologic alterations in roots and fasciculus gracilis, since the observed features may be secondary to axotomy of peripheral nerve fibers induced by disease and not evidence of a primary derangement. PMID- 4040790 TI - Reversal of the sexually dimorphic distribution of serotonin-immunoreactive fibers in the medial preoptic nucleus by treatment with perinatal androgen. AB - The effect of perinatal androgen exposure on the sexually dimorphic distribution of serotonin (5-HT)-immunoreactive fibers in the medial preoptic nucleus (MPN) of the rat was evaluated with an indirect immunohistochemical method. Female animals treated with testosterone propionate (TP) perinatally, postnatally or with oil vehicle alone were gonadectomized as adults and the 5-HT fiber distributions compared with those of intact male and female animals. In the adult female rat, the TP treatments resulted in a significant masculinization of both the 5-HT stained fiber distribution and the sexually dimorphic cytoarchitectonic features of the MPN. This masculinization appears to be complete only in the animals exposed to TP perinatally, suggesting that the critical period for the sexual differentiation of this nucleus may extend into the late prenatal period. PMID- 4040791 TI - Paraventricular nucleus lesions exaggerate dietary obesity but block photoperiod induced weight gains and suspension of estrous cyclicity in Syrian hamsters. AB - Lesions of the paraventricular nucleus (PVN) of the hypothalamus block short photoperiod-induced testicular regression in Syrian hamsters. We examined the effects of PVN or sham lesions on the short photoperiod-induced increases in body weight and adiposity in female Syrian hamsters. PVN lesions did not affect body weight when hamsters were housed in a long photoperiod (LD, 16:8) and fed Purina laboratory rodent chow (No. 5001). However, when fed a high-fat diet both groups gained weight, and the hamsters with PVN lesions gained approximately twice as much as the sham-operated controls. When the hamsters were exposed to a short photoperiod (LD, 8:16), only the hamsters with sham lesions displayed the typical increase in body weight. No further increase in body weight or parametrial fat pad weight was seen when the hamsters with PVN lesions were exposed to the short photoperiod. The lack of a short photoperiod-induced increase in body weight gain in hamsters with PVN lesions seems unlikely to be due to a "ceiling effect" on body weight gain because we have routinely observed neurally intact, melatonin treated female Syrian hamsters with body weight in excess of 250 g. Finally, the short photoperiod interrupted estrous cyclicity in sham-lesioned hamsters but not in those with PVN lesions. Thus, PVN lesions exaggerate dietary obesity but prevent short photoperiod-induced weight gains and vaginal acyclicity in female Syrian hamsters. PMID- 4040792 TI - [Liver damage due to cytostatic agents]. PMID- 4040793 TI - [The effect of drugs on laryngeal resistance and motor neuron activity in the recurrent nerve in the cat]. PMID- 4040794 TI - [The female prostate and its enzymes]. PMID- 4040796 TI - Splenectomy for idiopathic thrombocytopenic purpura. PMID- 4040795 TI - Intravenous usage of gammaglobulin: humoral immunodeficiency, immune thrombocytopenic purpura, and newer indications. AB - Intravenous gammaglobulin is effective therapy of ITP and other autoantibody mediated immune cytopenias. All children as well as adults unresponsive to splenectomy or with known immune deficiency are probably the best candidates for treatment with IVGG. Its major advantage, in addition to its efficacy of treatment and possible remission-inducing effect, is that it has the fewest side effects of any treatment of ITP so that it is the best maintenance therapy of patients when effective. Future uses of IVGG remain to be determined. Premature infants with a high mortality from sepsis and with hypogammaglobulinemia due to termination of pregnancy prior to transplacental antibody transfer may benefit from IVGG. A preliminary study suggested such benefit and also showed safety of IVGG treatment in that there was no impaired immune responsiveness of these prematures at 2 years of age (28). Another potential usage of IVGG involves the treatment of the hypogammaglobulinemia associated with certain types of malignancy. Patients with CLL, especially in the advanced stages, are often hypogammaglobulinemic. Multiple myeloma and Waldenstrom's macroglobulinemia are two other B-cell malignancies associated with antibody production defects which might benefit from antibody replacement therapy. Therapeutic IgG levels may be harder to obtain due to hypercatabolism of immunoglobulin. The issue of immune hyporesponsiveness during intensive chemotherapy is also unexplored. Secondary antibody responses do not seem to be impaired, but primary responses, as tested in numerous immunization studies, are decidedly impaired. Certain protocols, especially those treating high-risk acute leukemias and neuroblastoma during induction therapy are intensive with high rates of sepsis, and may warrant trials of prophylactic IVGG. Similarly, some form of humoral prophylaxis is becoming an important part of the handling of the patient undergoing bone marrow transplantation not only to prevent bacterial sepsis but also to prevent cytomegalovirus (CMV) interstitial pneumonitis. A likely additional usage is gammaglobulin replacement for patients undergoing plasmapheresis, especially if performed multiple times. Finally, the broad spectrum of antibacterial and antiviral antibodies present in the preparations (such as anti-CMV, anti-Group B strep, and antiendotoxin) and the ease and safety of delivery allow the preparations to be used in situations where a hyperimmune preparation might be desired and/or where more than one pathogen is possible. In summary, IVGG is a treatment capable of safely conferring significant benefits to selected patients.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 4040797 TI - An interview with Dr. Henry Morgentaler [by Rick L Hengel]. PMID- 4040798 TI - Prognostic significance of DNA patterns and resistance-predictive tests in non small cell lung carcinoma. AB - In a cooperative study, 240 surgical specimens of patients with non-small cell lung carcinomas (NSCLC) were investigated by means of flow cytometry, xenotransplantation to athymic mice and, an in vitro short-term test for predicting resistance. Aneuploidy was found in 83% of the tumors, and 20% showed more than one aneuploid DNA stemline. Patients with both aneuploid tumors and tumors with more than one DNA stemline had a significantly shorter survival rate than those with only diploid or only one DNA stemline. Patients whose tumors showed a low G0/G1-cell proportion or a high proliferation pool (S and G2/M-cell proportion) died earlier. A relationship could not be discerned between growth of tumors in nude mice or establishment of cell lines and the prognosis for the patients. Patients with in vitro-resistant tumors died earlier under chemotherapy than those with in vitro-sensitive tumors. Patients treated by radiation survived longer if the tumors were resistant in vitro. Thus, DNA patterns and in vitro short-term tests for predicting resistance represent useful tools for prognostic evaluation of patients with NSCLC. PMID- 4040799 TI - Cisplatin in recurrent pediatric brain tumors. A POG Phase II study. A Pediatric Oncology Group Study. AB - Forty-six evaluable pediatric patients with primary recurrent brain tumors resistant to standard therapy were treated with cisplatin, 60 mg/m2/day, X2 days every 3 to 4 weeks, to study the efficacy and toxicity of this drug. Complete and partial responses, documented by computed tomography (CT) scan, were demonstrated in 4 of 10 patients with medulloblastoma and 3 of 15 patients with ependymoma. No activity was documented in astrocytic tumors. Dose limiting major toxicities were renal and auditory. It is recommended that the new analogues of cisplatin with less toxicity be studied in these tumors. PMID- 4040800 TI - Anterior chemotherapy in esophageal cancer. AB - Front loading chemotherapy using methotrexate (200 mg/m2) alone or methotrexate (200 mg/m2) with cisplatin (20 mg/m2 daily for 5 days) was used in epidermoid carcinoma of esophagus. Evaluation after two courses showed objective response of 50% or greater in 48% of patients with methotrexate alone. Response rate was increased to 76.2% with addition of cisplatin to methotrexate. Small lesions (less than 10 cm) showed better response as compared to advanced cases. Therapy was generally well tolerated and good palliation was obtained even after the first course. Postchemotherpy treatment either with surgery or radiotherapy was tolerated without any major complications. The data confirm the short-term usefulness of initial chemotherapy with methotrexate and cisplatin in esophageal cancer. Results of prolonged follow-up will help to evaluate the role of front loading chemotherapy on long-term survival. PMID- 4040801 TI - Ototoxicity of low- and moderate-dose cisplatin. AB - Twenty-four patients with head and neck neoplasms were prospectively evaluated for cisplatin (DDP)-induced ototoxicity. Patients were selected from a larger population based on the uniformity of their chemotherapy regimen, renal status, lack of prior or concurrent exposure to ototoxic agents, and availability for repetitive audiometric testing in the same setting. Scanning electron microscopy of the inner ear was performed on four temporal bones. Hearing impairment was found to be dose-related, irreversible within the confines of the study period, and primarily in the higher frequencies. Vestibular toxicity was rare and well documented by our testing methods in only one patient. Based on the results of this study, and a review of animal and human data on DDP ototoxicity, the authors concluded that ototoxic screening should be reserved for patients defined as "at risk" and those patients receiving more than 400 mg of DDP under the conditions stated in this report. PMID- 4040802 TI - Angiosarcoma of the breast. Two case reports and a review of the literature. AB - Two cases of angiosarcoma of the breast are presented. They are of particular interest in that one patient is a long-term survivor, the 19th reported to date, and the other presented with contralateral breast involvement without evidence of disseminated disease. The world literature is reviewed and a discussion is presented of the clinical features, treatment, histopathologic features, and prognosis of this rare breast neoplasm. Tumor size and degree of tumor differentiation are the most important prognostic indicators, and in general a simple mastectomy is the treatment of choice. The value of adjuvant irradiation and chemotherapy is uncertain. PMID- 4040803 TI - On the meaning of fragile sites in cancer risk and development. AB - In the last few years, there has been increasing concern about the possible involvement of fragile sites in cancer risk and development. Patients with malignancies and family histories of cancer who presented with constitutional fragile sites are reported here. These findings are discussed with regard to the familial risk for cancer and the tissue specificity of the malignancy in relation to the different fragile sites. The hypothesis is advanced that these may be sites of viral DNA modification, probably representing areas where genes that are important for the metabolism of the virus are located. On the other hand, these genes may well be cellular (proto)oncogenes. We believe that fragile sites may increase the risk for cancer, not by being break-prone points at oncogene locations, but through more complex mechanisms that are not easy to predict. PMID- 4040804 TI - Chromosomal abnormalities in essential thrombocythemia. PMID- 4040805 TI - Biliary excretion of platinum in rats after administration of cisplatin and aqua(1,1-bis(aminomethyl)-cyclohexane)sulfatoplatinum(II) (spiroplatin, TNO-6). AB - Three groups of 6 rats were treated with cisplatin (3 mg/kg, bolus and 3-h infusion) and spiroplatin (3 mg/kg, bolus) by infusion in the right external jugular vein. The mean amounts of platinum +/- c.v. excreted in the bile during the first 6 h after the start of administration were 0.32 +/- 0.19% and 0.39 +/- 0.29% of the dose after bolus injection and 3-h infusion of cisplatin, respectively, and 3.77 +/- 3.32% of the dose after spiroplatin. The values were not significantly different between the 2 cisplatin administration modes (P greater than 0.05), but were between the spiroplatin and cisplatin bolus groups (Wilcoxon two-sided rank test, P less than 0.01). These data are related to pharmacokinetic parameters in man. PMID- 4040806 TI - Ascorbato(1,2-diaminocyclohexane):platinum(II) complexes, a new series of water soluble antitumor drugs. AB - Dichloro-1,2-diaminocyclohexane (DACH):platinum(II), the prototype DACH:platinum complex, had good antitumor activity, was not cross-resistant with cis dichlorodiammineplatinum(II) (DDP), but was, unfortunately, virtually insoluble in water and was, therefore, not evaluated clinically. This paper summarizes some of the chemical and biological attributes of a series of cis-bisascorbato DACH:platinum(II) complexes (DAP). Although the primary emphasis has been placed on the DAP complex consisting of the isomeric mixture DACH, a series of complexes using the isomers of either DACH or ascorbic acid have also been synthesized. The synthetic procedure entailed reacting the water-soluble sulfato-DACH:platinum(II) with barium ascorbate, and the water-soluble product DAP was removed from the BaSO4 precipitate by filtration. Based upon elemental analysis, all the complexes had stoichiometric composition of one DACH:one platinum and two ascorbate monoanions. High-pressure liquid chromatography of cis-bisascorbato (mixed-isomer DACH):platinum revealed a series of platinum-containing, ultraviolet-absorbing peaks. All the DAP complexes had significant in vitro cytotoxicity against L1210 leukemia cells (L1210/0) with 50%-inhibitory dose values ranging from 2 to 5 micrograms/ml. None of the complexes was cross-resistant with DDP when tested in vitro against L1210 cells 50-fold resistant to DDP (L1210/DDP). The cis bisascorbato (mixed-isomer DACH):platinum (DAP-1) was administered i.p. to C57BL X DBA/2 F1 mice inoculated i.p. with 10(6) L1210/0 cells. When administered on Days 1, 5, and 9, the DAP-1 complex consistently produced treated:control values in excess of 200% with several long-term survivors (alive 60 days after tumor inoculation). Further, the DAP-1 complex was totally non-cross-resistant with DDP when tested in vivo against a DDP-resistant L1210 line. Toxicological investigations revealed that DAP-1 was relatively nonnephrotoxic but did cause the expected bone marrow and gastrointestinal toxicity. In summary, the DAP complexes are highly water-soluble, nonnephrotoxic platinum complexes with sufficient antitumor activity to warrant further pharmacological, biochemical, and chemical investigations. PMID- 4040807 TI - Antiestrogenic potency and binding characteristics of the triphenylethylene H1285 in MCF-7 human breast cancer cells. AB - The antiestrogenic character and potency of 4-(N,N-diethylaminoethoxy)-4'-methoxy alpha-(p-hydroxyphenyl)-alpha' -ethylstilbene (H1285) and its binding to estrogen receptor and to estrogen-noncompetible antiestrogen binding sites have been studied in MCF-7 human breast cancer cells. H1285 has an affinity for the estrogen receptor (Kd 0.23 nM) which is comparable to that of estradiol (Kd 0.25 nM), and the binding of these two compounds to estrogen receptor is mutually competitive. On high salt sucrose gradients, the sedimentation profiles of nuclear receptor complexes with H1285 and estradiol are different. While the sedimentation profile of the complex with estradiol varies with the buffer composition, being 4.1S in phosphate:thioglycerol: glycerol and predominantly 5.5S in Tris:EDTA buffered gradients, the H1285 receptor complex shows the same sedimentation (5.5S) regardless of the buffer composition. H1285 also binds to estrogen-noncompetable antiestrogen binding sites that are distinct from the estrogen receptor with a low affinity, only 15% that of the antiestrogen tamoxifen. The biological character and potency of H1285 were examined by determining its effects on cell proliferation, cellular progesterone receptor levels, and plasminogen activator activity. In MCF-7 cells, H1285 was a 30- to 100-fold more potent inhibitor of cell proliferation than was the antiestrogen tamoxifen, and it was approximately equipotent with the higher affinity antiestrogen trans-hydroxytamoxifen. H1285 evoked very minimal increases in cellular progesterone receptor levels, and no increase in plasminogen activator activity over a broad range of concentrations (10(-10)-10(-6)M), and it suppressed plasminogen activator activity stimulated by estradiol. Therefore, by the criteria we have used, we conclude that H1285 is a potent and very effective antiestrogen in MCF-7 cells. The ability of estradiol to reverse the suppression of cell proliferation by H1285, and the high affinity of H1285 for estrogen receptor and its low affinity for estrogen-noncompetible antiestrogen binding sites suggest that H1285 exerts its antiestrogenic effects via interaction with the estrogen receptor of these breast cancer cells. PMID- 4040808 TI - Clinical evaluation of high-dose cytarabine and cisplatin in recurrent cervical carcinoma. PMID- 4040809 TI - Phase I-II trial with cisplatin and 5-FU in recurrent head and neck cancer: an effective outpatient schedule. AB - Thirty patients with squamous cell carcinoma of the head and neck were treated with a combination of cisplatin (20 mg/m2) and 5-FU (400-200 mg/m2) by iv push on Days 1-5 every 21 days. All patients but two had relapsed disease. Twenty-seven patients were evaluable for response: there were four complete responses and 12 partial responses (objective response rate, 59.2%). The response rate falls to 53.3% if it is calculated on the total number of patients entered. Twenty-seven patients were evaluable for toxicity: myelosuppression occurred in ten patients (37%), while renal toxicity, nausea and vomiting, and stomatitis were quite rare and moderate. These results look encouraging and suggest the need for further studies. PMID- 4040810 TI - Fluorescent labeling of carbohydrates and analysis by liquid chromatography. Comparison of derivatives using mannosidosis oligosaccharides. AB - To enhance resolution and detectability of carbohydrates by liquid chromatography, two fluorescent labels, introduced into oligosaccharides by reductive amination, were compared by use of standard sugars and a complex, biological sample of D-mannose oligomers obtained from the urine of a mannosidosis patient. Both labels, 2-aminopyridine and 7-amino-1-naphthol, improved the chromatographic efficiency and detection sensitivity. However, reductive amination with the pyridinylamine derivative was incomplete. The Schiff base intermediates left in the mixtures were only partially resolved by chromatography and complicate the patterns. In contrast, the naphtholamine derivatives were completely reduced and, in addition, possess enhanced fluorescence. PMID- 4040811 TI - The effects of lectins on the interaction between macrophages and bone in vitro. A morphological and functional study. AB - Recent studies have demonstrated that the attachment of elicited rat macrophages to bone is mediated by specific saccharides located on the cell and/or bone surfaces. We have used a macrophage-bone culture system to study the effects of two lectins, concanavalin A (con A) and soybean agglutinin (SBA), on the morphology of macrophage attachment to a devitalized bone surface and subsequent functional activity. Macrophages were obtained from 3- to 4-week-old rats by peritoneal lavage and the adherent pool was used to prepare cell suspensions. Con A-treated, SBA-treated or control cell suspensions were aliquoted onto the endocranial surface of devitalized rat calvariae. The cells were allowed to attach for 1 h at 37 degrees C, after which, the bone samples were removed from culture and prepared for scanning electron microscopy (SEM). The morphology of con A-treated macrophages attached to bone was markedly different from that of control or SBA-treated cells. Con A altered the attachment and subsequent spreading of macrophages on bone as visualized by SEM. Furthermore, the number of con A-treated cells that attached to bone and the average surface area of cell membrane apposed to the matrix was significantly different from that of control or SBA-treated cells. A 45Ca bone-release assay was performed to evaluate the functional significance of the morphological findings. Lectin-treated or control cell suspensions were allowed to attach to the endocranial surface of 45Ca pre labeled calvariae for 1 h. Following attachment, the samples were cultured for 72 h.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4040812 TI - Diffusion barriers in the vaginal epithelium during the estrous cycle in guinea pigs. AB - In the present study the permeability barriers of the multilayered vaginal epithelium were examined using tracer perfusion techniques, freeze-fracture and thin sectioning. During diestrus and proestrus the upper layers of mucified epithelial cells exhibit tight-junctional belts, which restrict tracer molecules such as lanthanum and horseradish peroxidase. When the highly mucified cells begin to degenerate toward the end of proestrus the underlying epithelium is already keratinized as typical for estrus. The keratinized epithelial cells have a tight-junctional network that joins the basal plasma membranes with the apical membranes of subjacent cells and blocks paracellular diffusion of the tracer molecules. During conversion of the cornified epithelium to a mucified epithelium in metestrus the intercellular space of the epithelium is stained by tracer molecules even though tight-junctional belts can be observed. These results indicate that during cyclic changes of the vaginal epithelium tight junctions can, in general, be considered for the restriction of paracellular diffusion. In metestrus, however, junctions become functionally leaky although they remain morphologically intact. Intercellular lipids, which are normally common in cornified epithelia, are extremely rare and cannot constitute an effective barrier to diffusion in the vagina of the guinea pig. The significance of a strategy that bases the regulation of the permeability on tight junctions rather than on intercellular lipids is discussed. PMID- 4040814 TI - Stereological analysis of daily variation in the ultrastructure of the pars intermedia of the pituitary gland of the Djungarian hamster (Phodopus sungorus). AB - A stereological analysis has been made of the daily changes occurring in the ultrastructure of the melanotrophs of the pars intermedia of the pituitary gland of the Djungarian or Siberian hamster, Phodopus sungorus, maintained in long day photoperiods. The rough endoplasmic reticulum, Golgi apparatus and lysosomes all declined in fractional volume throughout the photophase reaching minima at mid scotophase and rising to reach their maxima at about the time of onset of the photophase. The mitochondria reached their peak fractional volume just before the cessation of the photophase but then also declined to a minimum at mid scotophase. No significant changes were found to occur in the fractional volumes of the nucleus or the secretory granules. These morphological findings are compared with the changes in plasma and pituitary alpha-melanocyte-stimulating hormone levels found in the rat. PMID- 4040813 TI - Analysis of desmosomal intramembrane particle populations and cytoskeletal elements: detergent extraction and freeze-fracture. AB - We have examined sections and freeze-fracture replicas of Triton X-100 detergent extracted desmosomes from murine palatal epithelium. After extraction of lipids as well as soluble proteins, a cytoskeletal framework remained which consisted of intermediate filaments, microfilaments, and intact desmosomal skeletons. Traversing filaments, which link the intermediate filaments to large intramembrane particles of the P-face, appeared undisturbed within the desmosomal skeletons. Compared to unextracted controls, extracted specimens displayed P- and E-face desmosomal intramembrane particles which were more fully exposed. A broad range of sizes and shapes was apparent for the P-face associated particles. E face particles, some of which were exposed for the first time, were more homogeneous and generally smaller. Statistical data gathered from a large sample of P- and E-face particle diameters disclosed significant differences among the populations of the two faces. Both fracture faces of extracted desmosomal domains displayed a residual surface upon which the exposed particles seemed to remain lodged. The newly revealed structural features are presented in an hypothetical molecular model which provides for both vertical and horizontal stabilization of desmosomal subcomponents. The model may ultimately be relatable to emerging biochemical characterization. PMID- 4040816 TI - [Examination and treatment of men in infertile marriages in Czechoslovakia]. PMID- 4040815 TI - Cytochalasin D-induced increase in actin synthesis and content in a variety of cell types. AB - Treatment of a variety of mesenchymal cells (normal and transformed rat fibroblasts, bovine aortic endothelial cells, rabbit smooth muscle cells), exhibiting different cytoskeletal organizations and derived from several species, with doses of cytochalasin D (CD, 2-6 microM for 20 h) sufficient to induce cytoskeletal rearrangement and altered cellular morphology results in an increase in the relative content and rate of synthesis of actin. These data extend our previous findings for HEp-2 cells to other cell types and provide further evidence for our hypothesis that the CD-induced cytoskeletal reorganization triggers stimulation of actin synthesis and the resulting increase in actin content. PMID- 4040817 TI - [Postural development of premature neonates up to the 40th week after birth]. PMID- 4040818 TI - Estrogen and tamoxifen induced cytoskeletal changes in breast cancer cells. AB - The MCF-7 and CG-5 breast carcinoma cell lines were grown under different concentrations of estrogen and with or without the addition of tamoxifen to the media. Similar results were obtained with either cell lines. Cells cultured in estrogen-supplemented medium showed a marked change of the cell shape with the appearance of long projections sprouting from the cell body, adhesion areas being localized at the tips of these projections. A redistribution of bundles of prekeratin and actin fibres could be visualized by appropriate immuno cytochemical procedures. Vimentin intermediate filaments and microtubules did not appear significantly modified by hormone conditioning. Tamoxifen treatment resulted in structural and cytoskeletal changes similar to those observed in estrogen stimulated cells. These data indicate that the shape and the cytoskeletal architecture of breast cancer cells can be conditioned by hormone treatment. PMID- 4040819 TI - Neutral and acidic antitumor polysaccharides extracted from cultured fruit bodies of Grifola frondosa. PMID- 4040820 TI - Cholagogic and antiulcer effect of saussureae radix and its active components. PMID- 4040821 TI - Verapamil-induced improvement in left ventricular diastolic filling and increased exercise tolerance in patients with hypertrophic cardiomyopathy: short- and long term effects. AB - Verapamil improves exercise tolerance and decreases symptoms in many patients with hypertrophic cardiomyopathy. The mechanisms responsible for these effects are not completely understood, although previous studies indicate that verapamil enhances left ventricular relaxation and diastolic filling in such patients. To investigate the association between changes in left ventricular filling and exercise tolerance after verapamil, we studied 55 patients with hypertrophic cardiomyopathy by radionuclide angiography and graded treadmill testing before and after 1 to 4 weeks of therapy with orally administered verapamil, 320 to 640 mg/d. The verapamil-induced increase in peak left ventricular filling rate at rest (from 3.1 +/- 1.3 to 3.7 +/- 1.3 end-diastolic volumes/sec; p less than .001) was associated with an increase in exercise tolerance (from 5.9 +/- 3.6 to 8.7 +/- 4.7 min; p less than .001); exercise capacity increased in 34 of 43 patients (79%) manifesting an increase in peak filling rate but only one of 12 patients (8%) with unchanged or decreased peak filling rate (p less than .001). This initial trend persisted in 25 patients studied after 1 year of therapy; 11 of 16 patients (69%) with a persistent increase in peak filling rate had persistent improvement in exercise tolerance relative to preverapamil values, compared with only one of nine patients (11%) in whom peak filling rate was unchanged or decreased relative to preverapamil levels (p less than .02). Verapamil withdrawal after 1 to 2 years in 24 patients resulted in reduction in peak filling rate (p less than .001) and was associated with deterioration in exercise tolerance in 17 patients (71%). Hence, verapamil-induced changes in left ventricular peak filling rate were associated significantly with objective symptomatic improvement. These data support the concept that enhanced left ventricular diastolic filling is an important mechanism contributing to the clinical improvement experienced by many patients with hypertrophic cardiomyopathy during therapy with verapamil. PMID- 4040822 TI - Surgery of chronic adhesive otitis media. AB - The results of tympanoplasty operations in 55 ears with chronic adhesive otitis media were analysed. In 34% of the ears, the tympanic cavity was found to be aerated on follow-up examination. Hearing improved significantly in only 13 ears (24%). There were severe complications of surgery in two ears (3.6%): one ear became totally deaf and an iatrogenic cholesteatoma developed in the other. Because of these poor results, tympanoplasty is not recommended in the treatment of chronic adhesive otitis media. PMID- 4040823 TI - Guadalajara camptodactyly syndrome type II. AB - Two sisters and an unrelated girl presented a distinct intrauterine growth retardation-malformation syndrome with short stature, microcephaly, pectus excavatum, hip dislocation, hypoplastic pubic region and genitalia, camptodactyly, talipes, shortened 2nd toes, hypoplastic patella and skeletal dysplasia probably due to homozygosity from an autosomal recessive gene. PMID- 4040824 TI - Paracentric inversions in man. AB - Two new cases of familial paracentric inversions, 46,XY,inv(3)(p21.1p25) and 46,XY,inv(7) (q22.3q36.1) are presented. A review of published cases suggests that prenatal diagnosis for carriers of paracentric inversions is not warranted. However, care must be exercised in eliminating the possibility of insertions. PMID- 4040825 TI - Mechanism of action of natriuretic fraction of urine. AB - The nature of calcium dependence of natriuretic fraction (NF)-induced contractions in the rat smooth muscle anococcygeus and a possible correlation between the effect of NF on sodium transport and its natriuretic potency was investigated. NF and noradrenaline-induced contractions were partially dependent on external calcium concentration. Ouabain and potassium (K) free solution (KoPSS)-induced contractions were totally dependent on external calcium and were more effectively inhibited by calcium antagonists than those of NF and noradrenaline suggesting pharmacomechanical coupling as the mode of calcium dependence of NF. Like other agonists which contract by pharmacomechanical coupling, NF stimulated sodium transport (86rubidium uptake) in dog saphenous vein. Such stimulation correlated positively (r = 0.495, n = 17, P less than 0.05) with the natriuretic potency of NF. NF, like noradrenaline, contracts smooth muscle by pharmacomechanical coupling and NF-induced natriuresis is associated with stimulation of the sodium pump. PMID- 4040826 TI - Retarded development of hypertension in stroke-prone spontaneously hypertensive rats following chronic alcohol consumption. AB - The influence of chronic alcohol consumption on blood pressure was examined in normotensive Wistar/Kyoto rats (WKY) and in stroke-prone spontaneously hypertensive rats (SHR-SP). Ethanol, administered in drinking water from 5 weeks of age to produce moderate blood alcohol levels, substantially retarded the development of hypertension in SHR-SP and caused a mild reduction of blood pressure in WKY. Alcohol withdrawal caused an acute rise in blood pressure in both strains, followed by a reduction to the subnormal levels previously induced by alcohol treatment. This sustained antihypertensive effect of alcohol was not attributable to reductions of body weight or fluid intake. PMID- 4040827 TI - Progressive dystonia with marked diurnal fluctuation. Report of a case. AB - A 9-year-old girl suffering from progressive fluctuating dystonia is reported. Some problems of diagnosis are discussed. The differential diagnosis is described and a comparison is made with cases from the literature. PMID- 4040828 TI - The use of scintigraphic studies in mid-ventricular obstructive cardiomyopathy to rule out pseudoaneurysm. AB - A "pseudo-pseudo" aneurysm of the left ventricle due to mid-ventricular obstruction from asymmetric septal hypertrophy is presented. A case of mid ventricular hypertrophic obstructive cardiomyopathy (MVHOCM) was evaluated by means of echocardiography, angiocardiography, gated cardiac blood pool scanning, and a TI-201 myocardial scan. The gated cardiac blood pool scan appearance of MVHOCM is similar to pseudoaneurysm of the left ventricle. TI-201 myocardial imaging, however, was able to distinguish between MVHOCM and pseudoaneurysm of the left ventricle. PMID- 4040829 TI - Cholescintigraphic abnormality in a case of Kawasaki syndrome. AB - A 26-month-old girl with Kawasaki syndrome (mucocutaneous lymph node syndrome) is presented. Liver function studies were abnormal and sonographic examination revealed hydrops of the gallbladder. The Tc-99m DISIDA cholescintigraphy demonstrated both early and delayed nonvisualization of the gallbladder. A photopenic area was noted in and below the gallbladder fossa and there was medial and upward displacement of the common bile duct. It appears that Kawasaki syndrome may result in nonvisualization of the gallbladder by cholescintigraphy. Accordingly, this diagnosis should be added to the list of conditions associated with nonvisualization of the gallbladder by biliary scintigraphy. PMID- 4040830 TI - Diagnosis of Caroli's disease by technetium-99m DISIDA cholescintigraphy. Report of three cases. AB - Three patients in whom Caroli's disease was diagnosed by cholangiographic methods were studied by scintigraphy with Tc-99m DISIDA. Cholescintigrams showed an intense concentration of the radionuclide in the form of round spots near the hepatic hilus in late images. In two patients with cholestasis, a delayed hepatic clearance of the radionuclide was observed, which improved when the exploration was performed after a choledocoduodenostomy. Tc-99m DISIDA is not only a good noninvasive method to diagnose Caroli's disease, but also a useful technique to evaluate the patency of the biliary tree during the follow-up of such patients. PMID- 4040831 TI - Structure of the lower urinary tract and pelvic floor. PMID- 4040832 TI - Urodynamics of the lower urinary tract. AB - The symptoms associated with voiding disorders and incontinence in female patients are notoriously misleading. Even experienced urodynamicists are unable to achieve a 50% success rate for predictive diagnosis based on symptoms and physical examination in any group expect pure stress incontinence. Urodynamic studies are an essential part of the investigative sequence required to make an accurate diagnosis. If this is not made, treatment will be empirical and the success of therapy correspondingly disappointing. The advent of urodynamic investigations has allowed a more rational approach to treatment, with documented improvement in the success of therapy. However, our precise understanding of the pathophysiology of incontinence and voiding disorders remains incomplete. Nevertheless, a systematic scheme of investigation, using standardized record keeping and urodynamic techniques, allows an accurate diagnosis in most patients. It is essential that additional testing should be performed when the urodynamic investigations fail to explain the patient's complaints. It is hoped that advanced techniques, and, in particular, the electrophysiological approach, may provide the explanation for phenomena as yet ill understood, such as bladder instability. The chapter outlines the importance of a thorough basic assessment of each female patient with a symptomatic enquiry guided by urodynamic insight and a careful physical examination. The basic techniques of flow studies, cystometry, both filling and voiding, and urethral profilometry are described. The more complex and difficult electrophysiological tests are outlined. PMID- 4040833 TI - Resting and stress urethral pressures as a clinical guide to the mechanism of continence. PMID- 4040834 TI - Pathophysiology of stress incontinence. PMID- 4040835 TI - Stress incontinence: why and how operations work. AB - We still remain uncertain of the precise mode of cure produced by many continence procedures. In achieving a cure, some operations produce unacceptable side effects of urge incontinence and voiding difficulty. True comparison of results of different procedures cannot be made until both subjective and objective results are presented, the criteria for patient entry are documented, and randomized studies, using matched patients as far as possible (taking into account factors such as the patient's age, parity and past history of bladder neck operations), are carried out. A follow up for at least two years and preferably five years is necessary. Because more than one factor may act to cause USI, operations need to be selective, bearing that in mind that a schematic approach is needed to match the operation with the pathophysiology or anatomical lesion responsible for incontinence. PMID- 4040836 TI - Abdominal procedures for stress incontinence. PMID- 4040837 TI - Operative injury to the lower urinary tract. PMID- 4040838 TI - Persistent pulmonary hypertension in a very low birthweight preterm infant. AB - Persistent pulmonary hypertension of the neonate (PPHN) characteristically is seen in full-term or postterm infants. Occasionally, PPHN complicates the course of hyaline membrane disease in preterm infants. This report documents the unusual occurrence of PPHN in a preterm very low birthweight infant without apparent pulmonary parenchymal disease. PMID- 4040839 TI - [Undesirable and toxic side effects of medicinal plants]. PMID- 4040840 TI - Combined electroconvulsive and drug therapy. PMID- 4040841 TI - Isoelectric focusing studies of aldehyde dehydrogenases from mouse tissues: variant phenotypes of liver, stomach and testis isozymes. AB - Isoelectric focusing techniques (IEF) were used to examine the tissue distribution and genetic variability of aldehyde dehydrogenases (AHDs) from inbred strains of mice. Twelve zones of AHD activity were resolved which were differentially distributed between tissues. Liver extracts exhibited highest activity for most enzymes, with the exception of isozymes found in stomach (AHD 4) and testis (AHD-4 and AHD-6). Genetic variants for AHD-1 (liver mitochondrial isozyme) and AHD-4 (stomach isozyme) were examined from inbred strains and F1 hybrid animals. The results were consistent with dimeric subunit structures (designated as A2 and D2 isozymes respectively). IEF patterns for activity variants of testis-specific AHD-6 were identical, with 3-banded phenotypes being observed. pI values for the AHD forms as well as for aldehyde oxidase and xanthine oxidase isozymes, which stain in the absence of coenzyme, were reported. PMID- 4040842 TI - Actin in polygonal arrays of microfilaments and sequestered actin bundles (SABs) in lens epithelial cells of rabbits and mice. AB - The pattern of localization of actin filaments was compared in whole mounts of lens epithelium of rabbit and mouse using the fluorescently-labeled actin specific probe, rhodamine-phalloidin. In the adult rabbit lens, fluorescent polygonal arrays consisting of central vertices and interconnecting filaments were present in the apical end of each epithelial cell. Electron microscopy confirmed that these arrays lined the cytoplasmic side of the apical membrane. In the mature adult mouse, polygonal arrays were not seen either with fluorescence or electron microscopy. Instead, the actin was packaged in a single, elongated, often curved bundle near the epithelial cell apex, referred to as a "sequestered actin bundle" or SAB. The SAB often appeared attached to the plasma membrane and to approach the perinuclear basket of microfilaments. The significance of the differences in these two patterns of actin is discussed in terms of differences in the accommodative ability and static lens shape in these two animals. PMID- 4040843 TI - [The laser and digestive tumors. Study of 280 cases and presentation of a film]. PMID- 4040844 TI - Ulcerative colitis complicated by idiopathic central serous chorioretinopathy with bullous retinal detachment. AB - A 44-year-old woman, hospitalized with severe diarrhea due to ulcerative colitis, was found to have a rare ocular complication, idiopathic central serous chorioretinopathy with bullous retinal detachment. The ocular symptom started with the flare-up of the ulcerative colitis. Steroid therapy was not effective on the ocular disorder, while her ulcerative colitis became dormant. Relationship between the two disorders is discussed. PMID- 4040845 TI - Biochemical and behavioral changes in rats during and after chronic d-amphetamine exposure. AB - Two groups of rats were implanted with ALZET minipumps to deliver vehicle or a theoretical amount of 1 mg/kg per h of d-amphetamine (A) for 12 days. After 3 days of A-exposure, motor movements and stereotypic behavior were markedly increased. Subsequent testing during A-exposure showed that motor movements and stereotypic behavior remained significantly increased but declined. After removal of the pumps, these effects disappeared and no differences at rest, during stress or A challenge, were apparent in either group. Animals sacrificed after 3 days of drug exposure, showed a drastic decrease in cardiac, but not adrenal, catecholamine levels. In the brain, norepinephrine (NE) levels were markedly decreased in the frontal cortex, hypothalamus, caudate, pons-medulla and cerebellum. Epinephrine (E) levels were unaffected and dopamine (DA) levels were decreased in most areas without reaching statistical significance. Plasma corticosterone levels were similar in both groups. Animals in both groups sacrificed about 25 days after pump removal were biochemically similar. Under our conditions, A-exposure produced marked behavioral and biochemical changes but there was no evidence of residual abnormalities after cessation of drug treatment. PMID- 4040846 TI - The effects of soy flour and N-nitrosobis (2-oxopropyl) amine on the pancreas of the hamster. AB - Syrian golden hamsters fed diets of raw or heated soy flour for 16 months had an incidence (4%) of pancreatic neoplasms in both groups. Animals injected with N nitrosobis (2-oxopropyl) amine (BOP) and fed heated soy flour for 15 months developed a high incidence (88%) of microscopic benign and malignant neoplasms, primarily of ductal origin. This was in marked contrast to a similar group of BOP injected animals which had been fed raw soy flour and in which the incidence of pancreatic neoplasms was less than 10%. PMID- 4040847 TI - [Vital capillary microscopic examination and transcutaneous pO2-measurements by intravenous prostaglandin E1 infusion]. AB - The ability of a single i. v. application of 40 micrograms alprostadil (PGE1, mean therapeutic dose 0.62 microgram/kg body weight) to cause changes in capillary microscopy parameters and tcpO2 was investigated in an open study in 15 patients with peripheral arterial occlusive disease, Fontaine stage II-IV (8 women and 7 men, average age 70.1 and 70.0 years, respectively). Capillary microscopy investigations and oxygen tension measurements were carried out before and immediately after i. v. infusion of PGE1 or a 5% solution of laevulose using an intra-individual comparison. PGE1 led to an increase in the number of erythrocyte-filled capillaries per mm2, an improvement in the initial condition of the capillaries evaluated according to Fagrell and to a significant increase in the tcpO2, whereas no haemodynamic changes occurred at all after laevulose. These findings substantiate the view that PGE1 is also effective when applied intravenously distal from the arterial occlusion. PMID- 4040848 TI - The ontogeny of biologically active androgen-binding protein in rat plasma, testis, and epididymis. AB - Androgen-binding protein (ABP) can be detected in the blood of sexually immature male rats by its ability to specifically bind [3H]5 alpha-dihydrotestosterone (5 alpha-DHT). Since the androgen-binding site is functional, we consider this ABP to be biologically active. ABP can be detected (641 +/- 107 ng/ml; n = 5) in plasma by the 15th day of postnatal life, it reaches a maximum concentration (1631 +/- 323 ng/ml; n = 5) on day 20 of age, and is no longer detectable after day 40. ABP can be detected in the testes of all age groups studied (15 days to adult). However, no ABP is detectable in the epididymis until the animals are 25 days old. Plasma ABP comigrates on nondenaturing gels with photolabeled ABP from the adult or immature rat epididymis. Serum that had been treated with Affigel blue to remove albumin and with hydroxylapatite to decolorize it was photolabeled using [3H]17 beta-hydroxy-4,6-androstadien-3-one. Photolabeled serum ABP migrated on polyacrylamide gels containing sodium dodecyl sulfate as 60,000 and 48,000 dalton androgen-specific peaks. In contrast, photolabeled adult epididymal ABP exhibited the 47,000 and 41,000 dalton peaks characteristic of ABP subunits. When photolabeled plasma and epididymal ABP were combined and electrophoresed on the same gel under denaturing conditions, prominent 60,000 and 47,000 dalton peaks were obtained, indicating that the two species of ABP retained their identities when combined. Photolabeled epididymal ABP from 25-day-old rats exhibited similar subunit mol wt in the same ratios as ABP from the adult. When epididymal ABP from the two age groups was combined and subjected to sodium dodecyl sulfate polyacrylamide gel electrophoresis, the resulting pattern was identical to that obtained when the samples were run individually, except that there was an increase in peak height. These data indicated that there is no significant difference in the subunit mol wt of epididymal ABP from the two age groups. PMID- 4040849 TI - Identification of androgen-binding protein from testis cytosol and sertoli cell culture medium of the cynomolgus monkey, Macaca fascicularis. AB - The biochemical and immunological properties of monkey androgen-binding protein (mABP) from the cynomolgus monkey, Macaca fascicularis, have been examined in testis cytosol and medium of primary Sertoli cell-enriched cultures. mABP in testis tissue was separated from the serum protein testosterone-estradiol-binding globulin (mTeBG) by affinity chromatography on Concanavalin A-Sepharose (Con A). mTeBG from serum extracts was completely retained by the lectin and could be displaced with buffer containing alpha-methyl-D-glucoside. In contrast, mABP from testis extracts either did not interact with the Con A and appeared in the void volume or was partially retained by the column and could be eluted with buffer alone. A third component retained by the Con A may represent mTeBG contamination, a form of mABP which binds to Con A, or both. The specific 5 alpha dihydrotestosterone (DHT)-binding activity in the void volume of the Con A column was designated mABP and was further studied. [3H]DHT binding to mABP was saturable and of limited capacity (0.163 +/- 19 pmol/mg protein). Scatchard analysis of the data was consistent with a single class of binding sites with an apparent dissociation constant (Kd) at 4 C of 2.6 +/- 0.2 X 10(-9) M. DHT was the most effective competitor of [3H]DHT binding to mABP, followed by 2 methoxyestradiol, testosterone, estradiol, and cyproterone acetate. Concentrated Sertoli cell culture medium subjected to steady state polyacrylamide gel electrophoresis produced a single peak of specifically bound [3H]DHT with a mobility similar to that of other androgen-binding proteins. [35S]Methionine labeled medium proteins were immunoprecipitated with a rabbit anti-human TeBG antiserum. Two bands, corresponding to mol wt of approximately 46,000 and 48,000, were observed by fluorography, with the lighter component being more intense. After androgen affinity chromatography of radiolabeled medium proteins, these two bands were again observed on sodium dodecyl sulfate-urea-containing polyacrylamide gels. These results demonstrate that 1) mABP may be separated from mTeBG by lectin affinity chromatography, as in humans; 2) hTeBG and mABP are antigenically related; and 3) mABP consists of subunits of different mol wt in unequal ratios. PMID- 4040850 TI - Messenger ribonucleic acid from tumors associated with humoral hypercalcemia of malignancy directs the synthesis of a secretory parathyroid hormone-like peptide. AB - Previous studies have provided evidence that tumors associated with humoral hypercalcemia of malignancy produce a factor that shares certain biological properties with, but is not, native PTH. In the present study, media from Xenopus oocytes microinjected with polyadenylated RNA prepared from three human or animal tumors associated with humoral hypercalcemia of malignancy are shown to have activity in the cytochemical bioassay for PTH. This activity parallels that of the PTH standard in the assay and is completely inhibited by the PTH analog [Nle8,Nle18,Tyr34]bovine PTH-(3-34)NH2. Media from oocytes injected with mRNA from control tumors contain no such activity. The mRNA encoding this activity in one of the animal tumors has been enriched approximately 10-fold by preparative polyacrylamide gel electrophoresis. These results demonstrate that tumors associated with humoral hypercalcemia of malignancy have the capacity for directing the synthesis of a secretory protein that fulfills certain criteria for being the humoral mediator in question. These techniques may provide the basis for molecular cloning of this factor. PMID- 4040851 TI - Production of plasminogen activator by migrating cephalic neural crest cells. AB - Neural crest cells migrate extensively during embryonic development and differentiate into a wide variety of cell types. Our working hypothesis is that during migration, embryonic cells secrete proteases which modify local microenvironments, thereby facilitating directed cellular movements. In this communication, we report studies on the migration of cephalic neural crest cells in the avian embryo. We demonstrate that these cells produce high levels of the serine protease, plasminogen activator (PA), at the time of their initial migration from the neural tube and during their migration to and colonization of the developing head and neck. PMID- 4040852 TI - Recognition site of nuclear factor I, a sequence-specific DNA-binding protein from HeLa cells that stimulates adenovirus DNA replication. AB - Nuclear factor I is a 47-kd protein, isolated from nuclei of HeLa cells, that binds specifically to the inverted terminal repeat of the adenovirus (Ad) DNA and enhances Ad DNA replication in vitro. We have studied the DNA sequence specificity of nuclear factor I binding using cloned terminal fragments of the Ad2 genome and a set of deletion mutants. Binding of nuclear factor I protects nucleotides 19-42 of Ad2 DNA against DNase I digestion. Filter binding assays show that deletion of the first 23 nucleotides does not impair binding while a deletion of 24 nucleotides reduces binding severely. However, binding studies on Ad12 DNA indicate that nucleotide 24 can be mutated. Fragments containing the first 40 bp are bound normally while the first 38 bp are insufficient to sustain binding. Taken together, these results indicate that the minimal recognition site of nuclear factor I contains 15 or 16 nucleotides, located from nucleotide 25 to nucleotide 39 or 40 of the Ad2 DNA. This site contains two of the four conserved nucleotide sequences in this region. Sequences flanking the minimal recognition site may reduce the binding affinity of nuclear factor I. In accordance with these binding studies, DNA replication of a fragment that carries the sequence of the terminal 40 nucleotides of Ad2 at one molecular end is enhanced by nuclear factor I in an in vitro replication system. PMID- 4040854 TI - Comments on "Purification and properties of plasminogen activators from epithelial cells", by A. Electricwala and T. Atkinson. PMID- 4040853 TI - Repetitive zinc-binding domains in the protein transcription factor IIIA from Xenopus oocytes. AB - The 7S particle of Xenopus laevis oocytes contains 5S RNA and a 40-K protein which is required for 5S RNA transcription in vitro. Proteolytic digestion of the protein in the particle yields periodic intermediates spaced at 3-K intervals and a limit digest containing 3-K fragments. The native particle is shown to contain 7-11 zinc atoms. These data suggest that the protein contains repetitive zinc binding domains. Analysis of the amino acid sequence reveals nine tandem similar units, each consisting of approximately 30 residues and containing two invariant pairs of cysteines and histidines, the most common ligands for zinc. The linear arrangement of these repeated, independently folding domains, each centred on a zinc ion, comprises the major part of the protein. Such a structure explains how this small protein can bind to the long internal control region of the 5S RNA gene, and stay bound during the passage of an RNA polymerase molecule. PMID- 4040855 TI - Multiplicity in cellulases of Schizophyllum commune. Derivation partly from heterogeneity in transcription and glycosylation. AB - The white-rot fungus, Schizophyllum commune, secretes a member of each of three classes of cellulases: a beta-glucosidase, an exoglucanase, and an endoglucanase. Antibodies were developed to members of each of these three enzyme classes. Secretion of these cellulases is induced when a mycelium is transferred from a glucose to cellulose medium. The maximum level of cellulase transcripts, as indicated by the ability to direct biosynthesis of these cellulases in the rabbit reticulocyte cell-free translation system, occurred when the rate of secretion was maximum. This implied that initial regulation, at least, of cellulase biosynthesis occurs at the transcriptional level. There were two distinct mRNA directed products for each of the cellulases, with sizes estimated to be, for the beta-glucosidase, 95700 and 93800, for the exoglucanase, 59300 and 58200, and for the carboxymethylcellulase, 40600 and 39400. The secreted cellulases are largely glycosylated, as indicated by their binding to concanavalin A and their incorporation of D-[3H]mannose. The labelled protein was fractionated on concanavalin-A-agarose; about 70% of the label was bound. A small amount of each of the cellulases appeared in the unbound fraction; the remainder appeared in fractions eluted with 10 mM methyl glucoside or with 100 mM methyl glucoside plus 500 mM methyl mannoside. These results indicated each of the cellulases had an additional heterogeneity in glycosylation, with the most heavily glycosylated and highest molecular weight form eluting last from the concanavalin-A-agarose. Although tunicamycin (5 micrograms/ml) blocked glycosylation, there was still some secretion but at a reduced rate which was more pronounced for the beta glucosidase than for the carboxymethylcellulase activity. The size of the tunicamycin-secreted product in each case was, within experimental error, equivalent to that of the mRNA-directed one. PMID- 4040856 TI - Modulation of adenylate cyclase of human platelets by phorbol ester. Impairment of the hormone-sensitive inhibitory pathway. AB - The influence of the phorbol ester, 12-O-tetradecanoylphorbol-13-acetate (TPA), a direct activator of the Ca2+-activated, phospholipid-dependent protein kinase (protein kinase C), was studied on regulation of human platelet adenylate cyclase. Intact platelets were pretreated with the phorbol ester and, thereafter, membranes were prepared and the regulation of the hormone-sensitive adenylate cyclase in these membranes was studied. The following data were obtained: The TPA treatment applied had apparently no effect on the activity of the catalytic moiety of the platelet adenylate cyclase nor on the stimulatory NS protein nor on stimulatory hormone receptors (prostaglandin E1) and the mutual interactions of these components of the stimulatory hormone-sensitive pathway. However, the TPA treatment of intact platelets largely impaired the GTP-dependent, hormone sensitive inhibitory pathway to the adenylate cyclase, involving the inhibitory Ni protein. The pretreatment led to a large reduction or loss of adenylate cyclase inhibition by GTP itself and by the inhibitory agonists, epinephrine and thrombin, inhibiting the untreated enzyme via separate receptors by an Ni mediated process. In contrast, platelet adenylate cyclase inhibition not involving the Ni protein was not affected by the TPA treatment. The observed effects of TPA were very rapid in onset and were not shared by a derivative of TPA which did not activate protein kinase C. The data obtained suggest than protein kinase C activated by the phorbol ester interferes with the platelet adenylate cyclase system, leading to a specific alteration of the Ni-protein mediated signal transduction to the adenylate cyclase. PMID- 4040858 TI - Polychemotherapeutic treatment for ovarian carcinoma (our experience). AB - Since September 1980 to June 1983 we have treated 32 patients with ovarian cancer. Most patients were submitted to time polychemotherapy cyclophosphamide, adriamycin and cis-platinum. The maximum of survival time was 24 months; six patients died; the period of survival of the remaining 24 patients is between 2 and months. PMID- 4040857 TI - Microlipid droplets in milk secreting mammary epithelial cells: evidence that they originate from endoplasmic reticulum and are precursors of milk lipid globules. AB - Microlipid droplets, structures with diameters less than 0.5 micron, resemble larger cytoplasmic lipid droplets of milk secreting mammary epithelial cells in triacylglycerol core and surface coat composition. Previously, evidence was obtained that microlipid droplets fuse with and support growth of cytoplasmic lipid droplets, which are immediate precursors of large milk lipid globules. Morphological observations suggested that microlipid droplets may also be secreted directly from mammary epithelial cells, yielding the very small lipid globules of milk. The secretion mechanism, which involves envelopment of triacylglycerol droplets in apical plasma membrane, appeared to be the same for microlipid droplets as for larger cytoplasmic lipid droplets. Microlipid droplets appeared to originate by blebbing from cisternae of endoplasmic reticulum. By immunogold cytochemical localization and by immunological identification of electrophoretically separated polypeptides, endoplasmic reticulum, micro- and cytoplasmic lipid droplets, and milk lipid globules had a number of common polypeptides. Kinetics of incorporation of radiolabeled palmitate or glycerol into triacylglycerols and phospholipids were consistent with a possible endoplasmic reticulum origin of microlipid droplets and with the view that microlipid droplets may be secreted directly from the cell or may fuse with cytoplasmic lipid droplets. PMID- 4040859 TI - Combined common bile duct and gastric outlet obstruction demonstrated during hepatobiliary scintigraphy. AB - A 64-year-old man presented with jaundice. Hepatobiliary imaging using 99mTc DISIDA revealed complete hepatobiliary tract obstruction with a photopenic area corresponding to a dilated gallbladder and a large photopenic region corresponding to a distended stomach as a result of gastric outlet obstruction. At surgery, carcinoma of the head of the pancreas was found to be the cause of the combined common bile duct and gastric outlet obstruction. PMID- 4040860 TI - In vitro plasma binding of some second generation antitumor platinum complexes. AB - The kinetics of five cisplatin analogs binding to human plasma fractions possessing a molecular weight greater than 50,000 daltons were studied. Each drug solution in plasma ultrafiltrate or phosphate buffer (pH = 7.4, mu = 0.154) was mixed with human plasma and filterable platinum concentrations were measured versus time by atomic absorption spectrophotometry. The only Pt IV compound studied did not bind. All the other Pt II complexes bound, but their binding kinetics were quite different. The experimental data were fitted to a theoretical equation based on the hypothesis that plasma nucleophilic agents possessing a molecular weight greater than 50,000 daltons are able to react with Pt compounds with an apparent second order rate constant. The apparent reaction rate constants and initial concentrations of these nucleophilic agents were calculated. The difference between the respective values obtained for each cisplatin analog could be explained by differences in their chemical formulas. Therefore our result should contribute towards a better understanding of the pharmacokinetics of the cisplatin analogs studied. PMID- 4040861 TI - Six-month chemotherapy for urogenital tuberculosis. AB - Rifampicin (RMP, 600 mg), isoniazid (INH, 300 mg) and pyrazinamide (PZA, 1,000 mg) administered daily in the hospital for a duration of 2 months was followed at home by daily administration of 600 mg RMP and 300 mg INH for a duration of 4 months. 113 patients with previously untreated and bacteriologically proven urogenital tuberculosis were admitted to the study. Therapy was completed and evaluated in 106 (94%) patients. No failure of chemotherapy was observed during the treatment; one bacteriologically proven relapse occurred after completion of treatment within the 45- to 63-month follow-up. This 6-month chemotherapy seems as efficient as the standard treatment which lasted for 18-24 months. PMID- 4040862 TI - A new colpocystourethropexy for female stress urinary incontinence. AB - A new technique for the treatment of female stress urinary incontinence is described. It consists of colposuspension obtained by suprapubic placement of two double monofilament sutures in a spiral fashion on the lateral vaginal walls, which are fixed proximally to a Cooper's ligament and tied distally one to the other over the rectus fascia. This technique has been successfully employed in a preliminary series of 26 patients and it appears to be easy to perform and with a wide application range. PMID- 4040863 TI - Phytohemagglutinin-induced changes in tyrosine protein kinase and its endogenous substrates in human lymphocytes. AB - We have measured changes in tyrosine protein kinase activity in the particulate and soluble fractions of phytohemagglutinin (PHA)-stimulated human lymphocytes using a synthetic tyrosine-containing peptide as substrate. Following PHA stimulation, the activity of this enzyme remained stable for 24 h and then fell sharply in both fractions. Phosphorylation of endogenous substrates was also studied by gel electrophoresis of the same subcellular preparations which had been incubated with [gamma-32P]ATP. Gels were treated with alkali to hydrolyse phosphoserine, dried and autoradiographed. In the particulate fraction from resting lymphocytes, two prominent bands were labelled, one of 55-60 kD and another of 38 kD. Direct analysis showed that these proteins were labelled largely on tyrosine residues. The 38 kD band became less intensely labelled 24 h following PHA addition, and had disappeared by 72 h. Two new bands appeared at this time: a 42 kD band which was phosphorylated mostly on threonine and a 32 kD band phosphorylated on tyrosine. The 55-60 kD band remained unchanged up to 96 h following PHA addition. The final band pattern in stimulated lymphocytes resembled that of the malignant T lymphoblastic cell line JM1. Our data suggest that tyrosine protein kinases in resting lymphocytes are part of a mechanism which transduces external growth signals to the cell interior, and that this mechanism is inactivated once the signal has been transmitted. The pattern of endogenous substrates which are phosphorylated on tyrosine and threonine residues in the malignant T lymphoblastic cell lines JM1 is likely to be characteristic of proliferating T lymphoid cells rather than of the malignant state, since similar bands appear in normal lymphocytes upon PHA stimulation. PMID- 4040864 TI - Casein production during differentiation of mammary epithelial cells in collagen gel culture. AB - Mouse mammary epithelial cells cultivated on floating collagen gels secrete, as judged by immunoblotting, the full array of caseins found in mouse milk. The secreted caseins are all phosphorylated and have estimated minimum molecular weights (MWs) of 45, 40, 27, and 23 kD in SDS-PAGE. Intracellular caseins of epithelia from collagen gel cultivation or from lactating mammary glands are a combination of mature caseins identical with the secreted molecules and novel caseins whose apparent size in SDS-PAGE is different from the secreted molecules. The novel caseins were shown to be non-phosphorylated species apparently insufficiently mature for secretion. Our data indicate that, with regard to casein expression, cultivation of mouse mammary epithelia on collagen gels essentially duplicates their behavior in the lactating mouse mammary glands. PMID- 4040865 TI - Microvillar elongation following parthenogenetic activation of sea urchin eggs. AB - Parthenogenetic activation of unfertilized sea urchin eggs with ammonium chloride at pH 8.0 resulted in a slow, but dramatic, reorganization of surface microvilli in four species of sea urchin eggs. Following NH4Cl treatment, elongation of microvilli on the egg surface was observed concomitant with the formation of microfilament bundles within the microvillar cores. A minimum of 2 h of treatment was required for elongation and microfilament bundle formation to occur. The maintenance of elongated microvilli was pH-sensitive; removal of the activating agent resulted in the retraction of extended microvilli while readdition of NH4Cl caused microvilli to elongate again. Accompanying microvillar elongation in activated eggs, there was an increased calcium uptake as measured by 45Ca uptake. Blocking calcium uptake by incubation in lanthanum chloride or zero-calcium seawater containing 2 mM EGTA prevented microvillar elongation. These results suggested that elongation of microvilli following parthenogenetic activation by NH4Cl is pH- and calcium-dependent and is similar to that observed during normal fertilization. PMID- 4040866 TI - Microtubules, microfilaments and the transport of acetylcholine receptors in embryonic myotubes. AB - Both microtubules and microfilaments have been implicated in the exocytotic and endocytotic transport of coated and smooth surfaced membrane vesicles. We have reexamined this question by using specific pharmacological agents to disrupt these filaments and assess the effect on the movement of acetylcholine receptor (AChR) containing membrane vesicles in embryonic chick myotubes. Myotube cultures treated with nocodazole (0.6 microgram/ml) or colcemid (0.5 microgram/ml) (to disrupt microtubules) show only a 20-25% decrease in the number of cell surface AChRs after 48 h. Addition of chick brain extract (CBE) to cultured myotubes causes a significant increase in the total number of cell surface AChRs (measured by [125I]alpha-bungarotoxin (alpha-BGT) binding), thus providing us with a way to manipulate receptor and transport vesicle populations. Cultures treated with CBE plus nocodazole or colcemid show a 1.7-fold increase in AChR number over drug treatment alone, the same increase seen in cultures treated with CBE alone, although the total number remains about 20-25% less than that seen in control cultures. In cultures treated with cytochalasin D (0.2 microgram/ml) or dihydrocytochalasin B (5.0 micrograms/ml) (to disrupt microfilaments), 35 and 65% decreases in cell surface AChR number were seen after 48 h. However, in cultures treated with CBE and cytochalasin D, the same total number of AChRs was found as in cultures treated with CBE alone. No significant effects were seen with any of these drugs on the receptor incorporation rate (the appearance of new alpha-BGT binding sites) after 6 h. The half-life for AChRs in control cultures was 23.0 h. In cytochalasin D and dihydrocytochalasin B it was 21.9 and 19.0 h, respectively; with colcemid and nocodazole, it increased to 37.1 and 28.1 h. These results suggest that non-myofibrillar microfilament bundles are not involved in the movement of AChR-containing membrane vesicles; further, the small effects seen with microtubule inhibitors tend to rule out a major role for microtubules in this transport. PMID- 4040867 TI - The effects of several ion channel blockers and calmodulin antagonists on fertilization-induced acid release and 45Ca2+ uptake in sea urchin eggs. AB - The effects of calcium antagonists, diltiazem and verapamil, and calmodulin antagonists, chlorpromazine, N-(6-aminohexyl)-1-naphthalenesulfonamide hydrochloride (W-5) and N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide hydrochloride (W-7), were tested on two responses of the sea urchin egg to insemination: (1) H+ release; (2) Ca2+ uptake. It was found that calcium antagonists inhibited both processes, while calmodulin antagonists only inhibited H+ release but not Ca2+ uptake. Verapamil and diltiazem were effective to inhibit H+ release when added to the egg suspension up to 120 sec and W-7 was effective around 150 sec after insemination. Calcium antagonists became ineffective earlier than W-7 in inhibiting H+ release. A calmodulin-dependent step may thus occur linking the Ca2+ uptake and H+ release. 4,4'-Diisothiocyanostilbene-2,2' disulfonic acid (DIDS), an anion channel blocker, also inhibited both Ca2+ uptake and H+ release. This result suggests that an uptake of anion(s) occurs along with Ca2+ uptake. PMID- 4040868 TI - Inhibition of prostaglandin synthesis produces a muscular dystrophy-like myopathy. AB - Administration of inhibitors of prostaglandin synthetase to chicken embryos produced myopathies in their skeletal muscles which were characterized by ringbinden, hypercontraction, loss of Z disks, M bands, and thick and thin filaments. The effects of the inhibitors were reversed by administration of PGE1. The pathology of the myopathy induced in the chicken embryos was identical to that observed in human muscular dystrophy and had some features in common with other congenital myopathies. Altered prostaglandin function may therefore be directly or indirectly involved in the pathogenesis of congenital myopathies. PMID- 4040869 TI - [Immunostimulating effects in the body induced by bonafton]. AB - Study of the primary immune response in CBA mice which were injected with bonafton (1.5-3 mg/kg i.p.) for 3 days has revealed stimulation of antibody formation. The maximal effect as regards the humoral immune response has been recorded on the drug use in a dose of 2 mg/kg. It has been discovered that bonafton (1-3 mg/kg) also activated the cell immune response--delayed type hypersensitivity. PMID- 4040870 TI - [Effect of bromocryptin on the alcohol consumption and catecholamine level in the brain of rats undergoing long-term alcoholization]. AB - It has been established in experiments on rats subjected to long-term alcoholization that chronic administration of bromocryptin in small doses (1 mg/kg) considerably minimizes ethanol consumption by animals. Reduction in alcoholic motivation correlates with normalization of the level of dopamine, decreased by chronic alcohol action in the rat hypothalamus and midbrain. The use of bromocryptin also prevents an increase in the dopamine content in the rat hypothalamus during alcohol withdrawal. PMID- 4040872 TI - Characterization of the chymotryptic core of the adenovirus DNA-binding protein. AB - A fragment of the DNA-binding protein of adenovirus type 5 has been obtained by controlled chymotryptic digestion of the entire molecule. Partial sequence determination indicates that the fragment consists of amino acids 174-525. The fragment is biologically active as measured by its ability to substitute for the entire molecule in a reconstituted DNA replication system. Crystals have been obtained that show diffraction to 2 A. PMID- 4040871 TI - [The significance of the central regulation of sexual behavior in experimental alcoholism in male white rats]. AB - It has been shown that ethanol consumption by rats with a decreased activity of the brain zones, which regulate sexual behavior, declines but alcoholic motivation increases on destruction of the brain zones responsible for feeding behavior. PMID- 4040873 TI - Isolation and partial characterization of distinct forms of tyrosine protein kinases from rat spleen. AB - Three peaks of tyrosine protein kinase activity (TK-I, TK-II and TK-III) can be resolved when the extract of rat spleen particulate fraction is subjected to DEAE cellulose gradient chromatography. TK-I and TK-II, insensitive to both EGF and insulin, have been further purified by Sephacryl S200 gel filtration and characterized. TK-I has an apparent mR of 65000, by far prefers Mn2+ over Mg2+ as activator, can use GTP besides ATP as phosphate donor and is stimulated 2-3-fold by polylysine. TK-II, whose mR approximates 50000, is equally activated by Mg2+ and Mn2+, does not use GTP and is insensitive to polylysine. TK-I and TK-II can phosphorylate the synthetic peptide Asp-Ala-Glu-Tyr-Ala-Ala-Arg-Arg-Arg-Gly (as well as its derivative with Orn in place of Arg), angiotensin II and poly(Glu, Tyr) 4:1 which exhibits different km values with TK-I and TK-II, (100 and 10 microM, respectively). When TK-I was incubated with [gamma-32P]ATP and MnCl2 a doublet of alkali-stable radiolabeled bands with molecular masses of 55 and 60 kDa were observed. Under identical conditions TK-II gives rise to a single alkali stable radiolabeled band of 51 kDa, which may represent the autophosphorylation product of TK-II itself. PMID- 4040874 TI - Demonstration and characterization of alpha-human atrial natriuretic factor in human plasma. AB - This paper describes a highly specific and sensitive radioimmunoassay for alpha human atrial natriuretic factor (alpha-hANF), the C-terminal 28-amino-acid residue portion of human prepro-ANF in human plasma. A novel extraction and prepurification procedure allowed for detection of levels of immunoreactive-alpha hANF as low as 0.5 fmol/ml. In normotensive subjects, levels in the range 1-23 fmol/ml (mean = 8.9 fmol/ml) were found. Combined gel permeation and HPLC analysis demonstrated that this ir-alpha-hANF was comprised virtually exclusively of authentic 28-residue alpha-hANF. No evidence for occurrence of larger precursor forms in human plasma was acquired. A heterogenous group of hypertensive patients displayed considerably higher levels (mean = 62.2 fmol/ml), of interest in view of the hypotensive properties of ANF. PMID- 4040875 TI - Induction of histone H1(0) differs with different treatments among different cell lines. AB - Histone H1(0) is an H1 subfraction whose level on the chromatin is inversely correlated with the mitotic index of the cell. We investigated the increase in H1(0) in 6 cell lines when cell division was blocked by 4 methods: 5 mM butyrate, 2% DMSO, serum withdrawal or density inhibition. The 6 cell lines (HeLa S1 and S3, CHO, 3T6, NIE-115 and Vero) responded differently to the treatments as regards the amount of increase in H1(0) and comparisons among the lines reveal no obvious similarities between the lines in the differential effects of the various treatments on H1(0) levels. PMID- 4040876 TI - [Effect of natriuretic factor on sodium secretion in the small intestine]. AB - In dogs with Tiri-Vella fistula, the natriuretic factor increases the secretion of the intestinal fluid and its content of sodium. In rats with increased content of natriuretic factor, the water and sodium absorption diminishes in the intestine whereas the secretion of 22Na into the intestine lumen is increased. PMID- 4040877 TI - Comments regarding Dr. Johnston's editorial. PMID- 4040878 TI - [Effect of changes in diet composition on Pu-239 excretion from the body]. PMID- 4040879 TI - [Evaluation of the mutagenicity and carcinogenicity of hexachlorobutadiene]. PMID- 4040880 TI - Effects of caffeine ingestion during pregnancy. AB - We studied the effects of caffeine ingestion during pregnancy. A total number of 9,921 healthy pregnant women with a gestational age after 24 weeks were subjected to the study. The women who drank more than 5 cups of coffee per day had a high incidence of impending abortion, premature labor, and fetuses small for gestational age. The heavy coffee drinkers among the pregnant women had high rates of spontaneous abortion, chromosomal abnormality and congenital multi anomalies. However, we would like to stress that the multiple socioeconomic variables might be more important than any direct effect of caffeine. PMID- 4040881 TI - [Effects of NRGC-lesion on the rates of the development of morphine tolerance and dependence in rats]. AB - The development of tolerance to and dependence on morphine over 1-8 days treatment with morphine were studied with time in rats in which the nucleus reticularis gigantocellularis (NRGC), including the nucleus reticularis paragigantocellularis, were electrically destructed. The NRGC of SD male rats was bilaterally lesioned (DC, 0.5 mA, 40 sec), and morphine analgesia was estimated by the tail flick method. Morphine analgesia in NRGC-destructed rats (D-rat) was reduced to about 50% of that in sham-operated rats (S-rat). The dose of morphine to produce equi-analgesia increased 2-21.8 times during 1-8 days treatment with morphine in S-rat. Throughout this period, ratios of the equi-analgesic dose in D rat to that in S-rat were almost the same, i.e., the rate of tolerance development to morphine analgesia in D-rat was to the same degree as that in S rat. Administration of naloxone after 1-6 days treatment with morphine elicited body weight loss and increase in plasma corticosterone (Pcs), degrees of which were dependent on the dose of naloxone or the period of morphine treatment. No difference in these abstinence signs were detected between S- and D-rat, i.e., the rate of development of dependence on morphine in D-rat was to the same degree as that in S-rat. These results suggest that the NRGC participates in the development of morphine analgesia, but does not participate in the development of tolerance to and dependence on morphine. PMID- 4040882 TI - Prolactin response to morphine and stress in Brattleboro hetero- and homozygous rats. PMID- 4040883 TI - Comparison of spontaneous growth hormone secretion during daytime and sleep in children with short stature. AB - The authors compared diurnal growth hormone (GH) secretion with GH secretion during sleep in 24 children with delayed growth. In group I (children with normal response to provocative tests), the level of daytime secretion was lower than that of nocturnal secretion. In 3 of 9 cases, daytime secretion was abnormal, whereas nocturnal secretion was normal. In 2 cases, both diurnal and nocturnal secretion were abnormal, but response to provocative stimuli was normal. In group II (children with a false partial GH deficiency, i.e. with inadequate response to provocative tests, GH peak less than 11 ng/ml and normal nocturnal secretion), the results were comparable with those of group I, with extremely low diurnal secretion in 6 of 9 cases. In group III (children presenting true partial GH deficiency, i.e. GH less than 11 ng/ml in response to provocative tests together with abnormal nocturnal secretion), both diurnal and nocturnal GH secretion were insufficient, with nonexistent diurnal secretion in 5 of 6 cases. Diurnal secretion does not seem to be a reliable indicator of 24-hour spontaneous secretion. PMID- 4040884 TI - The human spleen; a histological study in splenectomy specimens embedded in methylmethacrylate. AB - In a series of 316 surgically removed spleens, a histological and supportive immunohistological study was performed on methylmethacrylate sections. The structure of the human white and red pulp differs from the rat spleen in many respects, e.g. the human lacks the marginal sinus and the architecture of the periarteriolar lymph sheath seen in the rat. In man, the lymphoid compartment is in both white and red pulps. In the white pulp separate periarteriolar T-cell areas contain a large lymph-vessel plexus, which was reconstructed in serial sections. The circulation in the red pulp is discussed. The area between the red and white pulp, the perifollicular zone, is not the equivalent of the marginal sinus in the rat. Its anatomy in man suggests that it is an area formed from red pulp during the expansion of new follicles. The micro-anatomy was analysed in 119 controls. In cases of traumatic rupture the white pulp showed evidence of stimulation. A pathognomonic histological picture was not found in idiopathic thrombocytopenic purpura. In haemolytic anaemia the pulp cords were engorged by erythrocytes accompanied by a decreased B/T cell ratio in autoimmune haemolytic anaemia and by an increased B/T cell ratio in congenital spherocytosis. PMID- 4040885 TI - Gastric choriocarcinoma and yolk sac tumor in a man: observations about its possible origin. AB - The case of a 65-year-old man who had a gastric tumor with components of choriocarcinoma and yolk sac tumor is presented. The presence of a small component of adenocarcinoma in the primary tumor and the absence of any gonadal or other primary tumor at autopsy confirm its origin. Despite the common association of embryonal and trophoblastic elements in gonadal tumors, this is the first case in which such an association was clearly depicted in the stomach. This and the usual coexistence of adenocarcinoma with choriocarcinoma in the stomach suggest the possibility of a different mode of development of these tumors in the two sites: forward differentiation of neoplastic germ cells in the gonads and retrodifferentiation (opisthoplasia) of neoplastic mucosal epithelial cells in the stomach. PMID- 4040886 TI - Mediation by cellular retinol binding protein of a specific uptake of [3H]retinol by hen oviduct nuclei in vitro. PMID- 4040887 TI - Monitoring 24-hour blood pressure in a drug trial. Evaluation of a noninvasive device. AB - To test the usefulness of noninvasive ambulatory 24-hour blood pressure recording, the Del Mar Avionics system was used in a double-blind clinical trial in which 31 hypertensive patients were randomly allocated to receive placebo or pafenolol (25 mg or 50 mg), a novel, long-acting, highly selective beta-blocker, once daily. The results of 24-hour blood pressure and heart rate recording after 4 weeks of treatment were compared with a previous 24-hour recording performed after a 4-week placebo run-in period using the 3-hour mean of recordings performed every 7.5 minutes both day and night. Furthermore, 24-hour means were analyzed in each patient before and after 4 weeks. The system was easy to use and, judging from two placebo periods in the same patients, the reproducibility was good. The 24-hour blood pressure and heart rate recordings showed a clear dose-response relationship for pafenolol that could not be detected by ordinary casual readings. A daily dose of 25 mg of pafenolol significantly reduced blood pressure during the 9 hours after tablet intake (p less than 0.01), while 50 mg per day of pafenolol resulted in a significant reduction throughout the 24-hour period (p less than 0.01). The same pattern was seen for heart rate, which indicates a greater degree of beta-blockade during treatment with the higher dose. These results indicate that the tested noninvasive equipment is a useful tool for monitoring ambulatory 24-hour blood pressure. It gives important information impossible to obtain from single casual readings. This noninvasive method should be further evaluated to define its place in clinical work and as a research tool. PMID- 4040888 TI - Maternal effects on blood pressure and survivability in inbred Dahl salt sensitive rats. AB - Maternal effects on blood pressure response to high salt diet were evaluated using inbred Dahl salt-sensitive (S/JR) and inbred Dahl salt-resistant (R/JR) rats. A cross-fostering experiment did not yield any evidence for a consistent effect of strain-specific fostering environments on the subsequent blood pressure response of S/JR or R/JR rats. A small increment in blood pressure seen only in male rats associated with the maternal R/JR environment was probably the result of effects mediated through an increment in body weight. In an experiment in which litter size was varied, weaning body weight was found to be an important predictor of survivability of S/JR rats fed a high salt (8% NaCl) diet; higher body weight was associated with longer survival in both males and females. Higher body weight at weaning also was associated with a small increment in blood pressure of S/JR rats in male, but not in female, rats. Intrauterine environment was evaluated using the embryo transplant technique. No evidence for a difference between S/JR and R/JR intrauterine environments with regard to blood pressure response of S/JR pups to salt was found. It is concluded that the early nutritional level during nursing as altered by varying litter size has important effects on body weight and survivability of S/JR rats on high salt diet, but that these effects are not mediated through changes in blood pressure. We found no evidence for genetic effects on blood pressure operating through the early maternal intrauterine or fostering environments. PMID- 4040889 TI - Virulence of Staphylococcus aureus in a mouse mastitis model: studies of alpha hemolysin, coagulase, and protein A as possible virulence determinants with protoplast fusion and gene cloning. AB - Mutants of a genetically well-characterized strain of Staphylococcus aureus [SA113(83A)] were isolated after mutagenization. Alpha-hemolysin- (hla), coagulase- (coa), and protein A- (spa) negative mutants were characterized by more than 90 biochemical tests for production of extracellular proteins and biochemical profile to exclude pleiotropy. Protoplast fusion was then used to isolate double-defective (hla and coa) recombinants and recombinants with regained properties, i.e., production of alpha-hemolysin and coagulase. Studies of such mutants and recombinants in the mouse mastitis model showed that one alpha-hemolysin [SA113(83A) hla-5] and one coagulase-negative [SA113(83A) coa 147] mutant were lower in virulence compared with the wild-type strain SA113(83A). The double-negative mutant SA113(83A) hla-5 coa-147 showed a drastic decline in virulence and only induced very mild changes, as determined by microscopic examinations of infected mammary gland tissue. The recombinant with regained properties, however, was as virulent as the wild-type strain. This suggests that alpha-hemolysin and coagulase are virulence determinants of S. aureus. A high-level protein A-producing mutant (U300) showed the same virulence as the parent strain SA113(83A) in this model. One low virulence protein A negative mutant (U320) did not markedly increase in virulence when a plasmid containing the cloned gene for protein A (pSPA15) was introduced into this mutant. By these and earlier observations, it seems likely that protein A is not an important virulence determinant in mastitis of mice. The reduced virulence of the protein A-negative mutant U320 compared with the wild-type SA113(83A) may be due to pleiotropic loss of some other unknown virulence determinant(s). Our data confirm earlier findings that pleiotropic changes are common in protein A negative mutants. PMID- 4040890 TI - Effect of aztreonam on the colon microflora in patients undergoing colorectal surgery. AB - Aztreonam was given intravenously at a dose of 1 g at induction of anaesthesia, followed by subsequent doses of 1 g at eight hour intervals during 48 hours to 20 patients undergoing colorectal surgery. A series of serum and faecal specimens were taken for analysis of aztreonam concentrations. Tissue samples from the gut wall were taken at surgery. The maximum serum concentrations (mean value 114.7 mg/l) during surgery were reached 15 minutes after aztreonam administration. The aztreonam concentration in the tissue samples varied from 4.1-28.3 mg/kg and the concentration in the faecal samples from 0.4-34.4 mg/kg. Faecal samples were also collected during the investigation period for cultivation of aerobic and anaerobic bacteria. Enterobacteria were suppressed significantly during the prophylaxis period and there was a significant increase of staphylococci in ten of the patients. Three of these patients developed postoperative wound infections with staphylococci. Among the anaerobic bacteria, only minor changes were observed during the same period. After two weeks, the microflora was normalized in all patients. Five postoperative infections including an anastomose dehiscence in one patient occurred. PMID- 4040891 TI - High-performance liquid chromatography of Cladosporium herbarum. Identification of allergens with immunological techniques. AB - High-performance liquid chromatography (HPLC) using a gel permeation column was applied to separate components in a crude extract of the mould Cladosporium herbarum. Allergenic activity as well as individual allergens in collected fractions were analyzed by direct radioallergosorbent test (RAST) and fused rocked radioimmunoelectrophoresis (FRRIE), respectively. Thus, information of the molecular weight as well as the importance of the individual allergens were obtained simultaneously in a system showing a high degree of resolution. The study demonstrated that the crude extract of C. herbarum contained allergens mainly in the molecular weight range between 10,000 and 300,000 daltons. The results demonstrated the importance of carrying out both RAST and FRRIE to detect all allergens. PMID- 4040892 TI - Plasma-exchange plus high-dose intravenous gamma globulin for chronic thrombocytopenic purpura. PMID- 4040893 TI - Effect of physical exercise and sleep deprivation on plasma androgen levels: modifying effect of physical fitness. AB - The responses of plasma testosterone (T), sex hormone-binding globulin (SHBG) binding capacity, androstenedione (A), and luteinizing hormone (LH) to 21 km of marching exercise and to sleep deprivation stress were studied in army recruits. The effect of physical fitness on the exercise responses was evaluated, cross sectionally, by comparing the stress responses in 11 fit and 11 less fit subjects, and, longitudinally, in 11 subjects after 4 months of physical training. The submaximal marching exercise did not significantly alter the plasma hormone levels compared to the control day levels. The fit subjects had a tendency toward smaller decreases in the mean plasma T and T/SHBG ratio during both control and exercise days than the less fit subjects. After 4 months of conditioning, the mean plasma T and T/SHBG ratio tended to decrease less during both control and exercise days, which was more evident in the well-conditioned subjects. The exercise caused a decrease in mean plasma LH, especially in the less fit subjects. After sleep deprivation stress, the morning levels of plasma T, A, and LH were significantly depressed, as a result of which the normal diurnal variation of the hormones disappeared. PMID- 4040894 TI - Resistance of nonlambing exotic and domestic ewes to naturally acquired gastrointestinal nematodes. PMID- 4040895 TI - Enzymes regulating glucosamine 6-phosphate synthesis in the zygote of Ascaris suum. PMID- 4040896 TI - Hearing loss and visco-elasticity of middle ear fluid. AB - It has been suggested that the physical properties of middle ear effusion--its viscosity and elasticity--affect the degree of conductive impairment. Exogenous mucus having substantial visco-elasticity was instilled in the bullae of guinea pigs, and the resulting hearing loss was determined by measurements of the cochlear microphonic potential. In this preparation the hearing loss induced by mucus did not differ significantly from that found when the bulla was filled with saline. We find no evidence of a relationship between visco-elasticity of middle ear fluid and amount of conductive impairment. PMID- 4040897 TI - The aetiology of glue ear--a case-control study. AB - A case-control study was carried out to investigate many of the proposed causes of glue ear in childhood. One hundred and fifty cases with two matched controls were found to be remarkably similar in nearly all medical and social aspects of their past and present lives, thus providing no support for many of the currently held views on the aetiology of glue ear. Of the 5 factors which were found to increase the risk of a child undergoing surgery for glue ear, only one of these is thought to be related to the development of the condition, rather than to the chances of its detection. This factor was parental smoking (RR 1.64). The 4 other risk factors appear to influence the chance of glue ear being detected, diagnosed and referred for surgical treatment - the child's mother being employed outside the home, but only if the father is employed in non-manual work (RR 3.0); attending pre-school day-care (RR 2.00); having an older sibling who had been diagnosed as suffering from glue ear (RR 1.84); and having been born locally (in Oxfordshire) (RR 1.89). Possible explanations for these social and behavioural factors are discussed. PMID- 4040898 TI - The measurement of immediate and persistent radiation-induced chromosome damage in rodent primary cells using premature chromosome condensation. AB - The chromosome damage observed in cultured peripheral blood lymphocytes at their metaphase is considered to be the most reliable basis for biological dosimetry. However, physical and biological factors such as irradiation conditions and chromosome repair could make difficult the interpretation of chromosome aberration yield in terms of absorbed dose. To establish correction factors to take into account partial body exposure, dose rate, and post-irradiation time requires in-vivo studies. Yet, such studies may be hampered by the laborious techniques required to culture the blood of the more readily available laboratory animals. In this paper, a cytogenetic approach based on a simple method for polyethylene-glycol-mediated cell fusion and premature chromosome condensation induction in primary cells is shown to be useful for in-vivo studies involving rodents. This method enables the direct assessment of radiation-induced chromosome damage without having the cells proceed to mitosis. The applicability of the method is demonstrated in particular for the measurement of immediate and persistent radiation-induced chromosome damage in rat peripheral blood, spleen, and thymus lymphocytes. PMID- 4040899 TI - Short rib-polydactyly syndrome (Majewski type): report of a case with autopsy findings. PMID- 4040900 TI - Enzyme histochemical profile of the adult human female prostate (paraurethral glands). PMID- 4040901 TI - HLA-linked immune responsiveness to (T,G)-A-L: a family study. AB - The heredity of the immune response potential to the synthetic polypeptide poly(LTyr,LGlu)-poly(DLAla)-poly(LLys) [(T,G)-A-L] and its possible linkage to the major histocompatibility complex of man were studied in 24 families. Peripheral blood lymphocytes (PBL) obtained from 174 donors belonging to 24 unrelated families were educated to (T,G)-A-L on autologous antigen-pulsed adherent cells. The supernatants obtained from these activated PBL were tested for their antigen-specific helper activity in an in vitro antibody production system. All donors were typed for their HLA haplotypes. The results obtained indicated that the ability to respond to (T,G)-A-L by production of an antigen specific T cell helper factor is inherited as an autosomal dominant trait linked to the responder HLA haplotype. PMID- 4040902 TI - Decreased fertility and motility of spermatozoa from rats immunized with a prealbumin epididymal-specific glycoprotein. AB - This study investigated the effects on the progressive motility, zona-binding capacity, and fertility of spermatozoa from the cauda epididymidis of adult male rats that were actively immunized against an acidic glycoprotein secreted by the epididymis. The percentage of motile spermatozoa was less than 5% in nine of ten rats that received the epididymal antigen, and 40 to 50% in eight of the 10 control rats. In animals immunized against the antigen, there was a dramatic decrease, but not a complete suppression, in the capacity of epididymal spermatozoa to bind the zona pellucida as compared with the nonimmunized controls. Fertility was decreased two weeks after the end of the treatment, but partial restoration of fertility was observed 6 months later. PMID- 4040903 TI - Corrected relative net protein ratio (CRNPR) method based on differences in rat and human requirements for sulfur amino acids. AB - The requirement for sulfur amino acids was calculated for growing rats fed 8% protein diets. The rat and human requirements for sulfur amino acids were compared and a correction factor was developed to reflect the differences. This correction factor was used to determine corrected relative net protein ratio (CRNPR) values for a number of potential meat extenders and their mixtures with beef. The methionine + cystine requirement of growing rats was estimated to be 4% of protein for 8% protein diets. The methionine + cystine requirement of rats was about 50% higher than that of humans (2.65% of protein). Based on this comparison (rat/human), a correction factor of 1.5 was developed to correct RNPR values of those protein products that were deficient in sulfur amino acids for rat growth. The CRNPR values of beef, casein, soybean protein products, pea concentrate, and peanut meal were 100, 100, 91-97, 75, and 73, respectively. Mixtures (50:50 protein basis) of beef with casein, soybean concentrate, soybean isolate, pea concentrate, peanut meal, rapeseed concentrate, rapeseed isolate, sunflower isolate, or wheat gluten were equal to beef in CRNPR values. The CRNPR method is a good predictor of protein quality for humans of those protein products that are deficient in sulfur amino acids. PMID- 4040904 TI - beta-Ketoadipate pathway in Trichosporon cutaneum modified for methyl-substituted metabolites. AB - Trichosporon cutaneum, when grown with p-cresol, catalyzed intradiol fission of the benzene nucleus of 4-methylcatechol before the complete catabolism of these two substrates. Steps in their conversion to pyruvate and acetyl coenzyme A were investigated by using cell extracts, and some properties of various new microbial catabolites are also described. These included (-)-2,5-dihydro-3-methyl-5 oxofuran-2-acetic acid (beta-methylmuconolactone) and (-)-3-keto-4-methyladipic acid and its coenzyme A ester; the latter was degraded by an enzymatic reaction sequence that included the coenzyme A esters of methylsuccinic, itaconic, and citramalic acids. A notable feature of this sequence is the formation of beta methylmuconolactone which can be readily metabolized, in contrast to the analogous reaction in bacteria that gives the "dead-end" compound gamma methylmuconolactone; this compound cannot be enzymatically degraded and so renders the beta-ketoadipate pathway unavailable for methyl-substituted bacterial sources of carbon that are catabolized by way of 4-methylcatechol. PMID- 4040906 TI - Kinetic investigation of soybean trypsin-like enzyme catalysis. AB - Various esters and amides of benzoylarginine and of benzyloxycarbonylarginine were subjected to enzymic hydrolysis at pH 8.5 and 7.2 by soybean trypsin-like enzyme (STLE). The kcat values for the hydrolysis of esters and amides were essentially identical regardless of the kind of leaving group. These results suggest that the STLE-catalyzed hydrolysis of ester and amide substrates proceeds via an acylenzyme intermediate and that the deacylation step is rate-determining. Hydrolysis of various 4-methylcoumaryl-7-amides of varying chain length and amino acid sequence was carried out at pH 8.5. Analysis of kinetic parameters revealed that STLE does not exhibit any remarkable subsite requirement, but somewhat preferentially hydrolyzes shorter substrates. These observations are consistent with the fact that STLE does not hydrolyze protein substrates or oxidized insulin B chain but hydrolyzes oligopeptides (Nishikata, M. (1984) J. Biochem. 95, 1169 1177). It is possible that the active site of STLE is located at a deep position in the enzyme molecule. From the pH dependency of kcat/Km, the participation of a histidine residue in the catalytic process of STLE was suggested. PMID- 4040905 TI - Enzymology of the beta-ketoadipate pathway in Trichosporon cutaneum. AB - Cell extracts were prepared from Trichosporon cutaneum grown with phenol or p cresol, and activities were assayed for enzymes catalyzing conversion of these two carbon sources into 3-ketoadipate (beta-ketoadipate) and 3-keto-4 methyladipate, respectively. When activities of each enzyme were expressed as a ratio, the rate for methyl-substituted substrate being divided by that for the unsubstituted substrate, it was apparent that p-cresol-grown cells elaborated pairs of enzymes for hydroxylation, dioxygenation, and delactonization. One enzyme of each pair was more active against its methyl-substituted substrate, and the other was more active against its unsubstituted substrate. Column chromatography was used to separate two hydroxylase activities and also 1,2 dioxygenase activities; the catechol 1,2-dioxygenases were further purified to electrophoretic homogeneity. Extracts of phenol-grown cells contained only those enzymes in this group that were more active against unsubstituted substrates. In contrast, whether cells were grown with phenol or p-cresol, only one muconate cycloisomerase (lactonizing enzyme) was elaborated which was more active against 3-methyl-cis,cis-muconate than against cis,cis-muconate; in this respect it differed from a cycloisomerase of another strain of T. cutaneum which has been characterized. The cycloisomerase was purified from both phenol-grown and p cresol-grown cells, and some characteristics were determined. PMID- 4040907 TI - Paratropomyosin: a new myofibrillar protein that modifies the actin-myosin interaction in postrigor skeletal muscle. II. Distinct function from tropomyosin. AB - The functional differences between paratropomyosin and tropomyosin were studied. The weight ratio of maximally bound paratropomyosin to F-actin was 1 : 7.6, whereas that of tropomyosin was 1 : 3.9. The actin-myosin interaction was markedly depressed by paratropomyosin under conditions where it was promoted by tropomyosin. Paratropomyosin had sensitized the actin-myosin-troponin system to Ca2+, but was much less effective than tropomyosin. Paratropomyosin showed an additive effect on the actomyosin systems containing tropomyosin, indicating that the binding site of paratropomyosin on F-actin is distinct from that of tropomyosin. Probably, due to greater affinity for myosin binding site on F actin, paratropomyosin competes for the binding site and thus modifies the actin myosin interaction. The role of paratropomyosin in tenderization of meat during postmortem ageing is also discussed. PMID- 4040908 TI - Inhibition studies of soybean trypsin-like enzyme. AB - The results of inhibition studies of soybean trypsin-like enzyme (STLE) by substrate analogues (derivative of arginine) suggested that a net negative charge exists at or near the substrate binding region of the enzyme. On hydrolysis of substrates, this negative charge seems to repel the products from the substrate binding region and facilitate the turn-over of substrates. From the data on inhibition by various amidines, guanidines, and amines, some information about the structure of the hydrophobic binding pocket of STLE was obtained. The inactivation of STLE by irreversible inhibitors, diisopropylfluorophosphate (DFP) and tosyl-lysine chloromethyl ketone (Tos-Lys-CH2Cl), was decreased by competitive inhibitors. This means that these irreversible inhibitors bind with residues at the substrate binding region, probably serine and histidine residues, respectively. PMID- 4040909 TI - Radiation inactivation studies on the rabbit kidney sodium-dependent glucose transporter. AB - Rabbit kidney cortical brush-border membrane vesicles were irradiated in the frozen state with increasing doses of high energy electrons from a Van de Graaff generator. Sodium-dependent D-glucose and L-alanine transport showed a simple exponential loss of activity with increasing radiation dosage. Target size calculation based on these data gives estimates of 1.0 X 10(6) daltons for the glucose transporter and 1.2 X 10(6) daltons for the alanine transporter. A highly purified glucose transport protein extracted from rabbit kidney cortex was similarly irradiated both before and after reconstitution into liposomes. The target size of this purified glucose transporter was 343,000 daltons, based on inactivation of transport. The intensity of the major 165,000-dalton sodium dodecyl sulfate-gel electrophoresis band of this preparation was decreased by radiation. The decrease in staining intensity was dose-dependent, yielding a target size of 298,000 daltons, in situ. We propose that the purified glucose transporter reconstituted into liposomes is a tetramer comprised of 85,000-dalton subunits. PMID- 4040910 TI - Photoaffinity labeling of the human erythrocyte monosaccharide transporter with an aryl azide derivative of D-glucose. AB - A photoreactive, radioiodinated derivative of glucose, N-(4-iodoazidosalicyl)-6 amido-6-deoxyglucopyranose (IASA-glc), has been synthesized and used as a photoaffinity label for the human erythrocyte monosaccharide transporter. Photoinactivation and photoinsertion are both light-dependent and result in a marked decrease in the absorption spectra of the compound. When [125I]IASA-glc was photolyzed with erythrocyte ghost membranes, photoinsertion of radiolabel was observed in three major regions, spectrin, band 3, and a protein of 58,000 daltons located in the zone 4.5 region. Of the three regions which were photolabeled, only labeling of polypeptides in the zone 4.5 region was partially blocked by D-glucose. In the non-iodinated form, N-(4-azidosalicyl)-6-amido-6 deoxy-glucopyranose inhibited the labeling of the transporter by [125I]IASA-glc more effectively than D-glucose. The ability to synthesize this [125I]containing photoprobe for the monosaccharide transporter at carrier-free levels offers several new advantages for investigating the structure of this transport protein in the erythrocyte. PMID- 4040911 TI - Forskolin-induced change of the size of adenylate cyclase. AB - Forskolin, a potent activator of cyclic AMP generating systems, has been proposed to act directly on the catalytic unit of adenylate cyclase. Nevertheless, some arguments indicate a possible role of the guanosine triphosphate-binding regulatory protein in forskolin action on adenylate cyclase. In this study, we have observed an increase in the apparent sedimentation coefficient of solubilized adenylate cyclase, elicited by forskolin, both in rat liver (from 6.4 +/- 0.1 to 7.2 +/- 0.1 S) and rat striatum (from 6.7 +/- 0.1 to 7.6 +/- 0.1 S). On both systems, a similar increase in the sedimentation coefficient was observed after preactivation of the enzyme with guanosine 5'-(beta, gamma imido)triphosphate (Gpp(NH)p). In contrast to the Gpp(NH)p effect, the forskolin action was found to be reversible. Simultaneous pretreatments of adenylate cyclase with forskolin and Gpp(NH)p did not induce additive increases of the apparent sedimentation coefficient of adenylate cyclase. The modification of the size of solubilized adenylate cyclase was corroborated by gel filtration studies. In rat liver membranes, the Stokes radius of the solubilized enzyme increased from 59 +/- 1 A for basal state to 65 +/- 1 A for forskolin preactivated state. A possible explanation of our findings is that forskolin may stabilize the complex between the GTP-binding regulatory protein and the catalytic unit of adenylate cyclase in a reversible manner. PMID- 4040912 TI - Effect of glucocorticoids on hexose transport in rat adipocytes. Evidence for decreased transporters in the plasma membrane. AB - Glucocorticoids are known to rapidly inhibit glucose transport when added to isolated rat adipocytes. To determine whether this inhibition of transport persists following isolation of the plasma membranes, adipocytes were incubated in the absence or presence of a maximally inhibitory concentration of dexamethasone, a synthetic glucocorticoid, and plasma membrane vesicles were prepared. D-Glucose uptake into vesicles from steroid-treated cells was inhibited by an average of 40%. The ability of dexamethasone to inhibit transport depended upon pretreatment of cells with hormone prior to membrane isolation. Furthermore, the decreased rate of transport was prevented by the simultaneous addition to the cell of actinomycin D or cycloheximide with dexamethasone, indicating a requirement for RNA and protein synthesis. The effect of dexamethasone on glucose transport was further investigated using our recently developed cytochalasin B affinity-labeling protocol to identify the transporter on sodium dodecyl sulfate polyacrylamide gels. A peak of radioactivity having Mr = 54,000 was identified which exhibited the properties expected for the glucose transporter, in that label incorporation was prevented by D-glucose and unlabeled cytochalasin B, but not by D-sorbitol or unlabeled cytochalasins A, D, or E. Dexamethasone was found to cause a significant (average 33%) decrease in the amount of labeled transporter in the plasma membrane which was prevented by the simultaneous addition of actinomycin D with dexamethasone to the cells. A similar percentage decrease was not found in a microsomal membrane fraction nor in a total cellular membrane fraction. These results suggest that glucocorticoids may decrease glucose transport in rat adipocytes by selectively decreasing the number of transporters in the plasma membrane. PMID- 4040913 TI - Effect of oral contraceptives and some psychological factors on the menstrual experience. PMID- 4040914 TI - Bilateral fracture of the femoral neck during a hypocalcaemic convulsion. A case report. AB - Vitamin D deficiency occurs in up to 24% of the Asian immigrant population in the United Kingdom, but pathological fractures are relatively uncommon. We report a case of bilateral fracture of the femoral neck caused by a convulsion secondary to dietary-induced hypocalcaemia. To our knowledge such a sequence has not previously been reported. PMID- 4040915 TI - The kinetics of chemotactic peptide-induced change in F-actin content, F-actin distribution, and the shape of neutrophils. AB - Formyl-met-leu-phe (fMLP) induces actin assembly in neutrophils; the resultant increase in F-actin content correlates with an increase in the rate of cellular locomotion at fMLP concentrations less than or equal to 10(-8) M (Howard, T.H., and W.H. Meyer, 1984, J. Cell Biol., 98:1265-1271). We studied the time course of change in F-actin content, F-actin distribution, and cell shape after fMLP stimulation. F-actin content was quantified by fluorescence activated cell sorter analysis of nitrobenzoxadiazole-phallacidin-stained cells (Howard, T.H., 1982, J. Cell Biol., 95(2, Pt. 2:327a). F-actin distribution and cell shape were determined by analysis of fluorescence photomicrographs of nitrobenzoxadiazole phallacidin-stained cells. After fMLP stimulation at 25 degrees C, there is a rapid actin polymerization that is maximal (up to 2.0 times the control level) at 45 s; subsequently, the F-actin depolymerizes to an intermediate F-actin content 5-10 min after stimulation. The depolymerization of F-actin reflects a true decrease in F-actin content since the quantity of probe extractable from cells also decreases between 45 s and 10 min. The rate of actin polymerization (3.8 +/- 0.3-4.4 +/- 0.6% increase in F-actin/s) is the same for 10(-10) - 10(-6) M fMLP and the polymerization is inhibited by cytochalasin D. The initial rate of F actin depolymerization (6.0 +/- 1.0-30 +/- 5% decrease in F-actin/min) is inversely proportional to fMLP dose. The F-actin content of stimulated cells at 45 s and 10 min is greater than control levels and varies directly with fMLP dose. F-actin distribution and cell shape also vary as a function of time after stimulation. 45 s after stimulation the cells are rounded and F-actin is diffusely distributed; 10 min after stimulation the cell is polarized and F-actin is focally distributed. These results indicate that actin polymerization and depolymerization follow fMLP stimulation in sequence, the rate of depolymerization and the maximum and steady state F-actin content but not the rate of polymerization are fMLP dose dependent, and concurrent with F-actin depolymerization, F-actin is redistributed and the cell changes shape. PMID- 4040916 TI - Glycosaminoglycan synthesis is depressed during mitosis and elevated during early G1. AB - [35S]Sulfate incorporation was measured in populations of Chinese hamster ovary cells enriched for mitotics, early G1 cells, and interphase monolayers or suspensions. Incorporation was determined by biochemical analysis of extracts and quantitative autoradiography of thick sections. 90% of [35S]sulfate was incorporated into glycosaminoglycan (GAG). Incorporation was depressed fourfold in mitotics and stimulated by from two- to three-fold in early G1 cells relative to mixed interphase cells. GAG synthesis was maintained into late G2. Thus, the rate of GAG biosynthesis was correlated temporally with the detachment and reattachment of cells to substrate. Inhibitors of protein synthesis brought about the rapid arrest of GAG biosynthesis. However, xylosides, which bypass the requirement for core protein, did not bring oligosaccharide sulfation in mitotics to interphase levels. These observations indicate an inhibition of Golgi processing and are consistent with a generalized defect of membrane vesicle mediated transport during mitosis. PMID- 4040917 TI - Relationship of actin polymerization and depolymerization to light scattering in human neutrophils: dependence on receptor occupancy and intracellular Ca++. AB - When exposed to the N-formylated chemoattractant peptides, neutrophils undergo a transient ruffling followed by a polarization that involves a redistribution of F actin (Fechheimer, M., and S. H. Zigmond, 1983, Cell Motil., 3:349-361). The cells also undergo a biphasic right angle light scatter response whose first phase is maximal 10-15 s after exposure to the stimulus, and whose second phase is longer in duration and maximal only after 1 min or more (Yuli, I., and R. Snyderman, 1984, J. Clin. Invest. 73:1408-1417). We now report that the first phase is accompanied by a transient polymerization of actin (monitored by cytometric analysis of phallacidin staining according to the method of Howard, T. H., and W. H. Meyer, 1984, J. Cell Biol., 98:1265-1271) and the second phase is accompanied by a more sustained polymerization of actin. Based on correlated measurements of ligand binding (Sklar, L. A., D. A. Finney, Z. G. Oades, A. J. Jesaitis, R. G. Painter, and C. G. Cochrane, 1984, J. Biol. Chem., 259:5661-5669) and intracellular Ca++ elevation (under conditions where we use the fluorescent Ca++ chelator Quin 2 to modulate intracellular Ca++ levels), we conclude that this first phase requires less than 100 receptors/cell (out of 50,000) and does not require the release of intracellular stores of Ca++. In contrast, the sustained polymerization requires both the occupancy of thousands of receptors (an estimated 10% of the receptors per minute) and may be somewhat sensitive to the availability of intracellular Ca++. When ligand binding is interrupted, F actin rapidly depolymerizes with a half-time of no greater than approximately 15 s, and the transient light scatter response decays toward its initial value in parallel. Partial disaggregation of the cells follows the recovery of these responses. Based on these observations, we suggest that transient actin polymerization and transient cell ruffling give rise to transient aggregation as long as degranulation is limited. PMID- 4040919 TI - Sperm-oocyte interaction in the sea-urchin. AB - A study was made of the electrical and morphological changes in the sea-urchin oocyte during interaction with spermatozoa. The first event, a small step depolarization accompanied by a 20-40% decay in input resistance occurs within seconds of attachment. The evidence suggests that this electrical event is the result of sperm-oocyte fusion, and that the ion channels that lower the resistance across the oocyte-sperm complex are located in the sperm plasma membrane. This primary electrical event does not necessarily lead to sperm incorporation. A second, determinative, event occurs at 50 s, which leads to sperm entry and the formation of a cytoplasmic protrusion at the site of sperm entry. This second event probably results from the transfer of a soluble component from the spermatozoon into the oocyte cytoplasm, which leads to sperm incorporation and formation of the protrusion. The changes in the oocyte following insemination are compared with the events of egg activation. PMID- 4040920 TI - Isolation and partial characterization of Urechis caupo egg envelopes. AB - Eggs of Urechis caupo are surrounded by a congruent to 0.9 micrometer thick egg envelope and, attached to that, a peripheral jelly layer about 3 micrometers thick. Before fertilization, the sperm undergoes the acrosome reaction and binds to the egg envelope. As part of a study of the induction of the acrosome reaction and sperm binding in Urechis, we have developed a method to prepare an egg envelope fraction by differential centrifugation. The isolation procedure removes much of the jelly layer, but does not alter the fine structure of the envelope. When a sperm contacts an isolated envelope, it undergoes a normal acrosome reaction and binds to the envelope's outer face. Electrophoresis of the envelope fraction on sodium dodecyl sulphate (SDS)/polyacrylamide gels revealed six major components stained by Coomassie Blue, of which four are stained by the periodic acid-Schiff reagents (PAS). To measure the degree of enrichment of the envelope fraction, envelopes were isolated from eggs that had been externally radio iodinated; the specific activity of the envelope fraction was 17 +/- 3 times greater than that of intact eggs. The amino acid composition of the envelope fraction is dominated by Gly (19 mole %), Asx (11%), Thr (11%), Ser (8%), Ala (8%) and Glx (8%). The sugars fucose, xylose, mannose, galactose, glucose, N acetylglucosamine and N-acetylgalactosamine were detected by gas-liquid chromatography. We also investigated whether the egg envelope changes at fertilization. No change was detected in the electrophoretic 125I pattern of externally radio-iodinated eggs, and the envelope fractions prepared from unfertilized and fertilized eggs produced the same Coomassie Blue pattern on SDS/polyacrylamide gels. PMID- 4040918 TI - Structural changes that occur in scallop myosin filaments upon activation. AB - Myosin filaments isolated from scallop striated muscle have been activated by calcium-containing solutions, and their structure has been examined by electron microscopy after negative staining. The orderly helical arrangement of myosin projections characteristic of the relaxed state is largely lost upon activation. The oblique striping that arises from alignment of elongated projections along the long-pitched helical tracks is greatly weakened, although a 145 A axial periodicity is sometimes partially retained. The edges of the filaments become rough, and the myosin heads move outwards as their helical arrangement becomes disordered. Crossbridges at various angles appear to link thick and thin filaments after activation. The transition from order to disorder is reversible and occurs over a narrow range of free calcium concentration near pCa 5.7. Removal of nucleotide, as well as dissociation of regulatory light chains, also disrupts the ordered helical arrangement of projections. We suggest that the relaxed arrangement of the projections is probably maintained by intermolecular interactions between myosin molecules, which depend on the regulatory light chains. Calcium binding changes the interactions between light chains and the rest of the head, activating the myosin molecule. Intermolecular contacts between molecules may thus be altered and may propagate activation cooperatively throughout the thick filament. PMID- 4040921 TI - Local cerebral glucose utilization in normal female rats: variations during the estrous cycle and comparison with males. AB - The quantitative 2-[14C]deoxyglucose autoradiographic method was used to study the fluctuations of energy metabolism in discrete brain regions of female rats during the estrous cycle. A consistent though statistically nonsignificant cyclic variation in average glucose utilization of the brain as a whole was observed. Highest levels of glucose utilization occurred during proestrus and metestrus, whereas lower rates were found during estrus and diestrus. Statistically significant fluctuations were found specifically in the hypothalamus and in some limbic structures. Rates of glucose utilization in the female rat brain were compared with rates in normal male rats. Statistically significant differences between males and females at any stage of the estrous cycle were confined mainly to hypothalamic areas known to be involved in the control of sexual behavior. Glucose utilization in males and females was not significantly different in most other cerebral structures. PMID- 4040922 TI - High-performance liquid chromatographic determination of hallucinogenic indoleamines with simultaneous UV photometric and voltammetric detection. PMID- 4040923 TI - A rapid method for the purification of cytoplasmic paramyxoviral nucleocapsids. AB - A rapid method for the purification of cytoplasmic paramyxoviral nucleocapsids using a tabletop ultracentrifuge is described. The method yields materials equivalent in purity to materials purified by previously published procedures but requires only a fraction of the time (65 min vs 7-41.5 h). When used in conjunction with modern hypersensitive analytical techniques, the procedure provides equivalent or greater amounts of nucleocapsid for subsequent analysis or study. PMID- 4040924 TI - Bioavailability of albumin-bound testosterone. AB - The unbound fraction of plasma testosterone (T) can freely enter tissues, whereas the bioavailability of the albumin-bound T is controversial. A clinical observation in hirsute women receiving spironolactone suggested an experimental paradigm to test the effect of albumin binding on T bioavailability. We found an increase in the non-T-estrogen-binding globulin-bound fraction of plasma T in women from 24.1 +/- 3.9% to 42.0 +/- 8.1% (+/-SEM) while they received spironolactone. Computer modeling indicated that the absolute increase in the albumin-bound T concentration would be about 22.4-fold greater than that in the unbound T concentration (the ratio of albumin-bound to free T remaining virtually constant) because of the binding of T to albumin. We reasoned that the addition of graded amounts of spironolactone and its metabolites to plasma would provide a means to increase the albumin-bound T concentration appreciably. We evaluated the biological effects of this perturbation of T transport by spironolactone and its metabolites in a bioassay system using the Oldendorf technique. Bioavailable T increased proportionately with increments in free and albumin-bound T (r = 0.85; P less than 0.01). A major portion of the albumin-bound T (i.e. 55%) entered tissues under all conditions; the amount that was bioavailable vastly exceeded the amount of T that was unbound in the injected samples. An index of the amount of bioavailable T can be determined using the ammonium sulfate precipitation technique, as the percentage of non-T-estrogen-binding globulin-bound T in vitro correlated well with T bioavailability in vitro (r = 0.86; P less than 0.01). These studies support the conclusion that albumin-bound T is biologically important. PMID- 4040925 TI - Neurohypophysial hormones in cerebrospinal fluid of adults: absence of arginine vasotocin and of a diurnal rhythm of arginine vasopressin. AB - We previously reported a prominent diurnal rhythm of oxytocin (OT) in human cerebrospinal fluid (CSF) similar to the brisk CSF OT rhythm in monkeys. An OT CSF rhythm has not been found in lower species. In contrast, a pronounced arginine vasopressin (AVP) rhythm has been found in lower species, but the AVP CSF rhythm is less marked in subhuman primates. In patients (n = 7) in whom lumbar drains had been temporarily placed for treatment of CSF rhinorrhea, we obtained CSF samples every 6 h. In 6 of these 7 patients, we previously reported (1) finding a prominent CSF OT rhythm, with a peak at 1200 h, by analysis of variance of repeated measures. When the samples of CSF of these same 6 patients (plus 1 additional patient) were assayed for AVP, no AVP rhythm was found. We also measured AVP, OT, and arginine vasotocin (AVT) by RIA in single samples of CSF obtained from 23 other patients. In these single samples of CSF, mean AVP was 0.9 +/- 0.11 (+/- SEM) pg/ml, and OT was 3.7 +/- 0.5 microU/ml. CSF AVT immunoreactivity was 0.6 pg/ml or less in the 23 patients. Two pools of CSF were separated by reverse phase high pressure liquid chromatography. The peak OT and AVP, as determined by RIA, coeluted exactly with synthetic and human posterior pituitary OT and AVP, respectively. No immunoreactive AVT was found in the position of synthetic AVT in the eluates. Thus, OT and AVP are present in human adult CSF, but AVT is not. The lack of a prominent rhythm of AVP in human CSF is in marked contrast to the brisk OT rhythm. The rhythm of neurohypophysial peptides in human and subhuman primates is different from the rhythm in lower species, suggesting different functions for OT and AVP in the central nervous system of various species. PMID- 4040926 TI - An agenda for public health departments. PMID- 4040927 TI - Characterization of a new model of GM2-gangliosidosis (Sandhoff's disease) in Korat cats. AB - We have detected a disorder in Korat cats (initially imported from Thailand) that is analogous to human Sandhoff's disease. Pedigree analysis indicates that this disease in an autosomal recessive disorder in the American Korat. Postmortem studies on one affected cat showed hepatomegaly that was not reported in the only other known feline model of GM2-gangliosidosis type II. Histologic and ultra structural evaluation revealed typical storage vacuoles. There was a marked deficiency in the activity of hexosaminidase (HEX) A and B in affected brain and liver as compared to controls. Electrophoresis of a liver extract revealed a deficiency of normal HEX A and B in the affected animals. The blocking primary enzyme immunoassay verified the presence of antigenically reactive HEX present in affected cat livers in quantities slightly elevated with respect to the normal HEX concentration in control cats. In leukocytes, obligate heterozygotes had intermediate levels of total HEX activity with a slight increase in the percent activity due to HEX A. Indeed, 4 of 11 phenotypically normal animals in addition to four obligate heterozygotes appear to be carriers using this assay. Affected brain and liver compared with control brain and liver contained a great excess of bound N-acetylneuraminic acid in the Folch upper-phase solids; thin-layer chromatography showed a marked increase in GM2-ganglioside. In summary, we have characterized the pedigree, pathology, and biochemistry of a new feline model of GM2-gangliosidosis which is similar to but different from the only other known feline model. PMID- 4040928 TI - Species specificity of nonimmunologic contact urticaria: guinea pig, rat, and mouse. AB - In order to find the most suitable animal species for studies on nonimmunologic contact urticaria (NICU), human NICU agents: 20% benzoic acid (BA), 10% sorbic acid (SA), 15% cinnamic acid (CA), 20% cinnamic aldehyde (CAL), 1.0% diethyl fumarate (DEF), 0.2% methyl nicotinate (MN), all in absolute ethyl alcohol, and 100% dimethyl sulfoxide (DMSO) were each applied to the earlobes of guinea pigs, rats, and mice. Guinea pig ear reacted with swelling to all agents tested. The mean maximal increase in thickness of the guinea pig ear, measured with a micrometer, was 114 +/- 46%. No response to BA, SA, CA, DEF, or MN was noted in the rat or mouse ear. However, DMSO and CAL caused significant ear swelling both in the mouse and the rat. Thus, the guinea pig ear is more sensitive to a variety of human NICU agents than is rat or mouse ear. The striking differences in species reactivity to NICU agents suggest the possibility that there are several mechanisms (mediators) involved in reactions to different substances. The guinea pig ear swelling test remains the best quantitative animal method available for screening human NICU agents. PMID- 4040929 TI - Differential effects of in vitro ethanol on prostaglandin E1-sensitive adenylate cyclase from smooth muscle cells and platelets. AB - In membranes of smooth muscle cells cultured from rabbit mesenteric artery, ethanol dose-dependently activates adenylate cyclase, both basal and PGE1- or GPP(NH)P-sensitive. The alcohol increases the maximal stimulation induced by PGE1 and GPP(NH)P, without greatly affecting their potency. The arrhenius plot displays a discontinuity point, which is only slightly lowered by ethanol. On the contrary, in membranes from human platelets ethanol inhibits basal, GPP(NH)P- and PGE1-sensitive adenylate cyclase, without modification of the prostaglandin or guanine nucleotide potency. The break point present in the Arrhenius plots is definitely lowered by the alcohol. In addition, ethanol decreases the thermostability of the enzyme. Neither in myocytes nor in platelets does ethanol affect the activation energy of the reaction. The data suggest that ethanol probably interacts directly with the membrane proteins, and that its effect is not mediated only through a perturbation of membrane lipid fluidity. PMID- 4040930 TI - Response of lactating cows to pelleted and unpelleted soybean meal after partial protein depletion. AB - Twenty-four first-lactation cows, averaging 82 d postpartum, were protein depleted for 20 d by consuming a 9.4% crude protein diet. The cows were then assigned randomly and equally to a 2 X 3 factorial arrangement of dietary treatments in which either pelleted or unpelleted soybean meal containing 1% sodium bentonite was supplemented to corn or corn silage-based diets to yield 12.2, 15.4, or 18.1% crude protein, dry basis. Between 9 and 15 d of the depletion period, milk, milk protein production, and dry matter consumption decreased 20 to 25%. Blood hematocrit increased. On refeeding three amounts of protein, dry matter intake was greatest during week 4 of repletion. Milk production rapidly increased to a plateau averaging approximately 88% of preexperimental production with a somewhat greater response to the higher soybean rations. Neither intake, milk, milk protein production, plasma urea, serum albumin, or blood hematocrit provided any evidence that pelleted or unpelleted soybean meal differed nutritionally. PMID- 4040931 TI - Effects of duration of udder stimulation on milking dynamics and oxytocin release. AB - For effects of varying duration of premilking manual udder massage on milking performance and oxytocin release, five Holstein cows were subjected to a) no stimulation, b) stimulation by manual udder massage before machine attachment for 15 s, c) for 30 s, d) for 60 s, and e) for 120 s. Milk yield, fat, protein, and somatic cell content were not affected by treatments. The 30-, 60-, and 120-s treatments resulted in higher peak milk flow rate as compared to no stimulation. Stimulation for 60 or 120 s did not achieve higher peak milk flow rates than 15 or 30 s. Average milk flow rate increased with duration of stimulation, and no stimulation differed from 30-, 60-, and 120-s treatments. Machine-on time decreased with increasing stimulation. However, differences in average flow rates and machine-on times became nonsignificant when premilking stimulation time was added to machine-on time. No differences were significant between treatments and mean oxytocin concentrations. The marked difference in milk flow variables and machine-on time suggested a small yet finite threshold concentration of oxytocin leads to milk ejection. Udder massage of 30 s prior to machine attachment is more than adequate for preparing cows for milking with machine stripping. PMID- 4040932 TI - The structure and function of actin in hair cells. AB - Within the last 7 years, the protein actin has been identified in the stereocilia and cuticular plate region of the hair cell. An intensive effort has been mounted to describe the structural organization of this protein, to identify actin associated proteins in these regions, and to identify the functional role of these proteins. The paracrystalline array of actin and its cross bridges imparts rigidity and stiffness to the stereocilia, which are important in determining their response properties. It also appears that these properties can be changed if the paracrystalline array is damaged by noise exposure. The functional implications of stereocilia rigidity and stiffness, as well as potential contractile mechanisms in the hair cell, are discussed. Finally, it is suggested that changes in the cross-sectional shape of the stereocilia caused by shearing of actin filaments during stereocilia deflections can be related to the mechano electrical events in the plasma membrane of the cell. This may be the link between the transmission of vibrational energy through the sensory accessory structures of the peripheral ear, and the initiation of electrochemical events associated with transduction. PMID- 4040933 TI - The anatomical consequences of acoustic injury: A review and tutorial. AB - The anatomic consequences of acoustic overstimulation are explored in this presentation, and attention is directed toward issues where improvements in technology and empirical observation are needed before further advances in our understanding can be achieved. Gains have been made in the last decade in appreciating sound-induced cochlear injury, but there is now a need to evaluate not only cochlear pathology but also the functional state of the surviving structures. There is a wealth of information about the susceptibility of inner or outer hair cells to acoustic injury; however, the etiology of this injury is not yet fully understood. In addition, current ideas concerning the effects of noise on hair-cell stereocilia, hair-cell synapses, the cochlear vascular supply, and the central auditory pathways are in a state of flux and are either undergoing revision or emerging. Other issues, such as the basis of temporary or permanent threshold shift at the cellular level, and the individual differences in susceptibility to injury are in need of a fresh approach. It would seem that the time is now ripe to review our knowledge, recognize its gaps, and develop testable hypotheses concerning the mechanisms of acoustic injury to the ear. PMID- 4040934 TI - Professional review organizations: PRO or con? PMID- 4040935 TI - Changes in visual functions of children exposed as infants to prolonged illumination. AB - The visual system can be modified by early experience. Many infants requiring extensive medical treatment spend time in neonatal intensive care units in which they experience prolonged and relatively intense illumination. Visual functions were measured in a group of 7-year-old children who, as infants, were in intensive care for treatment of neonatal jaundice. Using procedures disguised as games, these children were tested for spatial and temporal resolution, receptor functions, and binocular vision. Especially in children whose eyes had not been shielded, deficits were found in color vision, spatial contrast sensitivity, and stereopsis, but not in rod vision. PMID- 4040936 TI - Prolactin pulsatility in polycystic ovarian disease. AB - Secretion patterns of LH and prolactin were studied in 5 nonobese (group A) and 7 obese (group B) women with polycystic ovaries (PCO) by taking blood samples at 15 min intervals for 6 h. Serum LH level showed a distinct pulsatility in all patients. There was no significant difference in the mean pulse rate of LH between group A (6.2 +/- 0.45, mean +/- SE) and group B (5.8 +/- 0.24). A pulsatile secretion pattern in prolactin was also found in 11 of the 12 PCO patients studied, the pulse rate being 3.2 +/- 1.0 in group A and 3.9 +/- 0.45 in group B. 79% of prolactin pulses coincided with those of LH but their amplitude was significantly lower than that of LH. In the total group of PCO patients a positive correlation was found between the serum concentrations of prolactin and free estradiol (r = 0.85), and prolactin and estrone (r = 0.78) indicating that estrogens participate in the regulation of prolactin secretion in polycystic ovarian disease. Four patients showed a steep decrease in the plasma prolactin level at the beginning of the study period suggesting a sensitive stress response. PMID- 4040937 TI - Influence of endogenous T3-autoantibodies on thyroid hormone measurements in a woman with transient postpartum thyroiditis. AB - Unreliable estimates of serum total T3 due to the presence of autoantibodies against T3 were observed in a woman who developed thyrotoxicosis followed by transient hypothyroidism after childbirth (postpartum thyroiditis). The T3 autoantibody levels changed during the postpartum period in a similar way to the thyroid microsomal antibodies. The total T3 values were constantly low, whereas the measurement of free T3 by the Amerlex analogue method deviated from the expected only at the time of maximal antibody levels. Thus, evaluation of thyroid function may be complicated by the simultaneous presence of thyroid hormone autoantibodies and transient postpartum thyroiditis. PMID- 4040938 TI - The reproductive system in elderly men. PMID- 4040939 TI - Endocrine testicular secretion in aging males. PMID- 4040940 TI - Endocrine and metabolic aspects in male senescence. PMID- 4040941 TI - [Evolution of the indications for cesareans. Comparison of 1971-1976 and 1976 1979 at the Maternity Center of the Louis-Mourier Hospital. Review of the literature]. AB - Changes in the indications for caesarean operations were studied over a period of 9 years from 1971-1979 and two periods from 1971-1975 and 1976-1979 were compared. The principal changes that show up are: an increase in the total number of caesarean sections from 5.3% in 1971 to 15.4% in 1979; modifications in the indications which were mainly due to much greater use of electronic means of monitoring the fetus and an improvement in the methods of resuscitation of the newborn (there were approximately the same number of caesareans for breech presentations, an increase in the number of repeat caesarean operations and of caesarean operations for fetal distress and for dystocia as well as for toxaemia of pregnancy); the improvement in the state of infants at birth seems to be parallelled by the increase in the number of caesarean operations. Though there was 8% neonatal morbidity, only 1% of these at the most could be put down to the caesarean; no maternal death occurred, although caesarean section is accompanied by an increased maternal morbidity of 27%. Reviewing the literature shows that the same tendencies occur in other places. This makes it possible to point out the ways in which action can be taken to limit the number of caesareans in those categories where the indications seem to be most frequent, namely dystocia, repeat caesareans, fetal distress and breech presentation. The optimum level of caesarean sections at 15% with 9% being first caesareans and 6% repeat caesareans should be kept to. PMID- 4040942 TI - Economic antecedents of help seeking: reformulation of time-series tests. PMID- 4040943 TI - Laboratory experiments to evaluate the ability of Arthrobotrys oligospora to destroy infective larvae of Cooperia species, and to investigate the effect of physical factors on the growth of the fungus. AB - Laboratory investigations were designed to study the influence of temperature, pH and oxygen tension on the growth of Arthrobotrys oligospora, a nematode-trapping microfungus. Experiments were performed to evaluate the potential role of A. oligospora in destroying third-stage larvae of Cooperia spp. on agar plates and in cattle faeces. The fungus had a growth rate optimum at 23 degrees C and pH 6. Anaerobic cultivation for 23 hours at 23 degrees C and 39 degrees C inhibited fungal growth, but it did not destroy the fungus, which regained growth upon a subsequent shift to aerobic conditions at 23 degrees C. Under experimental conditions in petri-dishes containing agar, the nematode-trapping efficiency of the fungus was striking in that 100% of a population of third-stage larvae of Cooperia spp. was captured within three days of the experiment. The trapping efficiency in faeces was shown to depend upon the inoculation level. At a concentration of approximately 2500 conidia per g faeces, 99% of the larvae were destroyed. The possibilities of using nematode-trapping fungi in controlling animal-parasitic nematodes are discussed. PMID- 4040944 TI - Homozygous chromosomal aberrations in Anopheles stephensi. AB - Homozygotes for six autosomal paracentric inversions, an inserted paracentric inversion, an autosomal translocation, and two X-chromosome-chromosome 3 translocations in Anopheles stephensi are described. Three of these aberrations are being maintained in pure strains without the necessity of selection. PMID- 4040945 TI - Carcinoma of the breast. Identical twins differing in time of onset and severity implicate non-genetic factors influencing clinical course. PMID- 4040946 TI - Re: The binding of immunoglobulins to cytoskeletal intermediate filaments. PMID- 4040947 TI - Immunofluorescent detection of anti-cytoskeleton antibodies using vinblastine treated mononuclear cells. AB - A reliable and reproducible immunofluorescence method is described for the detection of anti-cytoskeleton antibodies in human sera, based on the use of vinblastine-treated peripheral blood mononuclear cells as substrate. Three immunofluorescence patterns associated with antibodies to microfilaments, intermediate filaments and microtubules are readily identified. PMID- 4040948 TI - [Preclinical study of endoscopic laser coagulation of human ovaries]. AB - The hemostatic potential of YAG laser irradiation was investigated in 21 hysterectomy and adnexectomy patients of childbearing age. Endoscopic forceps were used to induce hemorrhaging in the ovarian capsule. The hemorrhage was then irradiated from a distance of 2cm using a series of 1-sec. irradiations at either 30W or 50W until complete hemostasis occurred. In the 30W group, hemostasis was achieved after a total irradiation of 4.1 +/- 1.6 sec. while a significantly shorter time of 2.5 +/- 0.8 sec. was required in the 50W group (p less than 0.01). The irradiation energy in the 30W and 50W groups was 107 +/- 45 J and 109 +/- 35 J, respectively. Tissue temperature was measured during laser irradiation at 5mm and 10mm from the center of irradiation at a tissue depth of 5mm. In the 30W group, the tissue temperature at the 5mm and 10mm points increased 6.6 +/- 2.0 and 2.5 +/- 1.1 degrees C, respectively, while the temperature in the 50W group increased 8.5 +/- 3.5 and 3.1 +/- 0.9 degrees C respectively. No remarkable histological changes were noted in either group following irradiation. YAG laser irradiation during endoscopy is therefore considered to be a highly effective hemostasis for minor hemorrhages caused by instrument manipulation during endoscopic surgery. PMID- 4040949 TI - [A study of the properties of human chorionic gonadotropin (hCG) from total hydatidiform mole with low hCG immunoactivity]. AB - A study was conducted to define biochemical characteristics of human chorionic gonadotropin (hCG) in total hydatidiform mole patients with low serum and urinary hCG levels and to inquire into the reason for its low immunological hCG level by comparing with the hCG of molar patients with a high hCG level. Both hCGs purified from chorionic tissue of molar patients with low and high hCG levels have essentially identical physicochemical, immunological and biological properties. They have low levels of biological activity and practically identical amino acid and carbohydrate compositions. It appears that moles of patients with high levels as well as those with low levels of immunoreactivity produce this purified form of hCG. Extracts of molar tissue from patients with high levels of hCG immunoreactivity also contained other substances with apparent immunoreactivity which can be found in small amounts in tissue extracts from patients who excreted low levels of hCG immunoreactivity. In contrast, extracts of molar tissue and urine from patients with low hCG levels contained hCG-like substances which cannot be detected with the ordinary commercial hCG immunoassay kits. These differences may account for the different levels excreted by these two types of patients. PMID- 4040950 TI - [Clinical trial of interferon in gynecologic cancers]. PMID- 4040951 TI - [An autopsy of thrombotic thrombocytopenic purpura associated with sepsis]. PMID- 4040952 TI - A multicompartmental model of vitamin A kinetics in rats with marginal liver vitamin A stores. AB - A linear, first-order, constant-coefficient multicompartmental model is presented which describes the dynamics of [3H]retinol turnover in adult rats with normal plasma retinol concentrations but low liver stores (less than 100 micrograms of retinol equivalents). To fit plasma and tissue (liver, kidney, and rest of carcass) tracer and tracee data, eight physiological compartments were required in the model: two in plasma (proposed to correspond to the retinol transport complex, and retinyl esters in plasma lipoproteins) and two each in liver, kidneys, and other extrahepatic tissues. Extensive recycling of retinol among plasma, liver, and the rest of carcass was also required. The model predicted that 44% of whole body vitamin A (143 micrograms) was in extrahepatic tissues. The vitamin A utilization rate (system disposal rate) was 6.9 micrograms of retinol equivalents/day. The system residence time (mean sojourn time) for vitamin A was 21 days, and the fractional catabolic rate for the system was 5%/day. The mean transit time (turnover time) for vitamin A in its plasma retinol transport complex was 0.078 days (1.9 hr); the residence time was 0.98 day, versus 11 days in the liver, 9 days in carcass, and 0.54 days in kidneys. The model predicted that, of the plasma turnover, 48% recycled to the liver and 52% to extrahepatic tissues. The liver retinol secretion rate was 48 micrograms/day, more than half of which was from recycled plasma retinol. Since the plasma retinol turnover rate (87 micrograms/day) was 13 times the system disposal rate, the data suggest that this is a high response system in which changes in the dynamics of recycling of retinol allow for rapid adjustment in vitamin A distribution in response to changes in nutritional, metabolic, or physiological conditions; and in which plasma retinol levels are controlled homeokinetically by changes in hepatic and extrahepatic recycling of holo retinol-binding protein. PMID- 4040953 TI - A technique for the rapid isolation and identification of psilocin from psilocin/psilocybin-containing mushrooms. AB - A method has been developed for the rapid isolation and identification of psilocin from psilocin/psilocybin-containing mushrooms. Based on the difference in the solubility properties in butyl chloride of psilocin and other constituents present in psilocin/psilocybin-containing mushrooms, psilocin was easily separated in pure form. PMID- 4040954 TI - Pituitary 5-hydroxytryptamine nerves--a possible link with pituitary hormone secretion. AB - A short review of the present knowledge on the innervation of the pituitary gland by 5-hydroxytryptamine (5-HT) containing nerves is given. This is followed by results of recent experiments in which the concentrations of 5-HT in different lobes of the rat hypophysis were measured under conditions in which pituitary hormone secretion was increased. A prolonged increase in hormone secretion induced by dehydration and increased sodium chloride intake resulted in a decrease in the 5-HT concentrations in the anterior lobe (AL). The 5-HT content of the neural (NL) and the intermediate lobe (IL) of these rats was hardly changed whereas that of DA was about doubled. Acute stimulation of pituitary hormone secretion by exsanguination under ether anaesthesia also caused a fall in the 5-HT content of the AL. In contrast, in the NL and in the IL of these rats, the 5-HT concentrations were significantly increased. This indicates that the 5 HT system in the AL reacts differently from those in the NL and IL. Pituitary dopamine (DA) contents were not affected by ether and exsanguination. Thus, the pituitary DA and the pituitary 5-HT neuronal systems are activated independently in different endocrine states. The concentrations of 5-HT were also measured in 10 groups of normal male or female rats in the course of 2 years and compared with those of DA. The concentrations of 5-HT were lowest in the AL with little variation between the different groups. In the rest of the tubero-hypophyseal system the concentrations of 5-HT were at least 3, and up to 10 times, higher than in the AL, with larger inter group variations. The DA concentrations in the AL were only 10-20% of those of 5-HT; in the other regions they were equal to or higher than those of 5-HT. PMID- 4040955 TI - Relationship among calmodulin-, forskolin-, and guanine nucleotide-dependent adenylate cyclase activities in cerebellar membranes: studies by limited proteolysis. AB - Adenylate cyclase activity in bovine cerebellar membranes is regulated by calmodulin, forskolin, and both stimulatory (Ns) and inhibitory (Ni) guanine nucleotide-binding components. The susceptibility of the enzyme to chymotrypsin proteolysis was used as a probe of structure-function relationships for these different regulatory pathways. Pretreatment of membranes with low concentrations of chymotrypsin (1-2 micrograms/ml) caused a three- to fourfold increase in basal adenylate cyclase activity and abolished the Ca2+-dependent activation of the enzyme by calmodulin. In contrast, the stimulation of the enzyme by GTP plus isoproterenol was strongly potentiated after protease treatment, an effect that mimics the synergistic activation of adenylate cyclase by Ns and calmodulin in unproteolyzed membranes. Limited proteolysis revealed low- and high-affinity components in the activation of adenylate cyclase by forskolin. The low-affinity component was readily lost on proteolysis, together with calmodulin stimulation of the enzyme. The activation via the high-affinity component was resistant to proteolysis and nonadditive with the Ns-mediated activation of the enzyme, suggesting that both effectors utilize a common pathway. The inhibitory effect of low concentrations (10(-7) M) of guanyl-5'-yl imidodiphosphate [Gpp(NH)p] on forskolin-activated adenylate cyclase was retained after limited proteolysis of the membranes, indicating that the proteolytic activation does not result from an impairment of the Ni subunit. Moreover, in the rat cerebellum, proteolysis as well as calmodulin was found to enhance strongly the inhibitory effect of Gpp(NH)p on basal adenylate cyclase activity. Our results suggest that calmodulin and Ns/Ni interact with two structurally distinct but allosterically linked domains of the enzyme. Both domains appear to be involved in the mode of action of forskolin. PMID- 4040956 TI - Studies on cytotoxic constituents in pericarps of Mallotus japonicus, Part I. AB - Two new phloroglucinol derivatives, named mallotophenone and mallotochromene, were isolated from the pericarps of Mallotus japonicus together with two known compounds, 3-(3,3-dimethylallyl)-5-(3-acetyl-2,4-dihydroxy-5-methyl-6- methoxybenzyl)-phloracetophenone and 2,6-dihydroxy-3-methyl-4 methoxyacetophenone. The new derivatives were confirmed to be 5-methylene-bis-2,6 dihydroxy-3-methyl-4-methoxyacetophenone and 8-acetyl-5,7-dihydroxy-6-(3-acetyl 2,4-dihydroxy-5-methyl-6- methoxybenzyl)2,2-dimethylchromene by their respective chemical and spectral data. Several of the phloroglucinol derivatives isolated from this tree were cytotoxic against the KB system and L-5178Y in cell culture. PMID- 4040957 TI - Adhesive interactions between normal and dystrophic human skin fibroblasts. AB - The adhesive properties of skin fibroblasts from patients with Duchenne muscular dystrophy (DMD) were studied by analysing cell aggregate formation in suspensions consisting of normal and DMD fibroblasts. By the use of aggregation kinetics and fluorescent labelling, the genotypic composition of aggregates in mixed-cell suspensions could be visualised. The distribution of normal and DMD cells within these aggregates could then be compared to theoretical binomial distributions which assume no difference in the specific adhesiveness between the two genotypes. Analysis of the 3- and 4-cell aggregates which were produced by co aggregating normal and DMD cells demonstrate that there is no qualitative (specific) difference in the adhesiveness between normal and DMD fibroblasts. However, quantitative changes in the cell-cell adhesion of DMD fibroblasts may be present, and this is supported by the relatively small proportion of intermediate size heterotypic aggregates which were formed in mixed-genotype cell suspensions. In such mixtures, fewer aggregates consisting of 5 or more cells were formed compared to fibroblast suspensions derived from pairs of normal individuals. Furthermore, cell suspensions from pairs of DMD patients produced even less greater than or equal to 5-cell aggregates than were found in the mixed-genotype experiments. These findings are considered in relation to previous reports of abnormal cell adhesiveness and other adhesion-related mechanisms in DMD cells. PMID- 4040958 TI - Renal and hepatic concentrations of platinum: relationship to cisplatin time, dose, and nephrotoxicity. AB - Autopsy tissues were obtained from 30 patients who had received cisplatin antemortem; the tissues were assayed for platinum by flameless atomic absorption spectrometry. Patients with antemortem evidence of renal toxicity had higher renal cortical platinum concentrations than did patients without evidence of kidney damage. In addition, patients with nephrotoxicity were more likely than patients without toxicity to have renal cortical platinum concentrations that were higher than renal medullary platinum concentrations. Overall, the two variables most closely associated with an increase in serum creatinine with treatment were renal cortical platinum concentration (P less than .02) and cumulative dose of cisplatin (P less than .05). These two variables were important independently of one another. Renal cortex platinum concentrations correlated inversely with time from last treatment until death, whereas hepatic platinum concentrations did not. In contrast, hepatic platinum concentrations correlated with dose of cisplatin while renal platinum concentrations did not. Our results suggest the following: (1) cisplatin-induced renal toxicity is tissue platinum-concentration dependent and cisplatin-dose dependent; and (2) cisplatin may be handled differently at the molecular level in liver and kidney. PMID- 4040959 TI - Lack of antiemetic effect of high-dose metoclopramide. AB - Sixteen of 26 patients given 51 courses of treatment of the doxorubicin and cisplatin combination with no antiemetic therapy suffered the same number of vomiting episodes and had the same duration of vomiting as did the remaining ten patients given 20 cycles of this chemotherapy plus the standard high-dose metoclopramide regimen. This antiemetic regimen caused significant side effects in one fifth of the patients receiving it. PMID- 4040960 TI - Neoplastic cerebral aneurysm from metastatic gestational choriocarcinoma. Case report. AB - This case of metastatic gestational choriocarcinoma presented as intracerebral hemorrhage from an atypical distal middle cerebral artery aneurysm. Operative evacuation of the intracerebral hematoma was undertaken and histopathological examination revealed choriocarcinoma invading the vessel wall. Neoplastic cerebral aneurysms are unusual, being reported in metastatic choriocarcinoma, cardiac myxoma, bronchogenic carcinoma, and undifferentiated carcinoma. Metastatic choriocarcinoma should be considered in the differential diagnosis of intracerebral hemorrhage in women of child-bearing age. Recent advances in treatment have resulted in a 75% cure rate for metastatic choriocarcinoma. PMID- 4040961 TI - The effects of coprophagy in the adult rat on rate of passage of digesta and on digestibility of food fed ad libitum and in restricted amounts. AB - The rate of passage of digesta and the digestibility of a nonpurified diet were studied in adult female rats prevented from coprophagy on alternate weeks by confinement to their normal feeding tunnels in metabolism cages. In food restricted rats a decrease in the time for the first appearance in the feces of a digesta marker was noted when prevention of coprophagy was followed by permitting rats to feed on their feces while being maintained on a restricted food intake, as compared to control rats permitted coprophagy throughout. The prevention of coprophagy had no effect on the rate of passage of digesta along the small intestine. The prevention of coprophagy had no effect on the apparent digestibility of dry matter, organic matter, energy or protein when the rats were fed ad libitum. However, when rats had lost 20% or more of their body weight by restricted feeding, digestibility of the measured constituents of the food offered in restricted amounts increased, but this effect was abolished when coprophagy was prevented. PMID- 4040962 TI - [Chemoembolization with cisplatin-microcapsule]. PMID- 4040963 TI - Monozygotic siblings discordant for neuroblastoma: etiologic implications. AB - Although rarely reported, neuroblastoma in monozygotic siblings merits attention because study of its features may aid in elucidating mechanisms of tumorigenesis. We describe disseminated neuroblastoma in one of monozygotic triplets, including both documentation of monozygosity and long-term follow-up of the unaffected co twins. Information from reports of monozygotic twins concordant and discordant for neuroblastoma reinforces the hypothesis that hereditary factors may be predominant in neuroblastoma diagnosed in infants, whereas nonheritable random mutational genetic events may be more important in neuroblastoma diagnosed after infancy. PMID- 4040964 TI - Physiologic testosterone or estradiol induction of puberty increases plasma somatomedin-C. PMID- 4040965 TI - Biliary atresia in two sets of twins. PMID- 4040966 TI - Histochemical localization of alkaline phosphatase activity in Leucochloridiomorpha constantiae (Trematoda) cultivated on the chick chorioallantois. PMID- 4040967 TI - Reversible inhibition of development and hatching of infective eggs of Ascaris lumbricoides var. hominis. PMID- 4040968 TI - Congenital unilateral orbital fibrosis with suspected prenatal orbital penetration. AB - Congenital fibrosis of the extraocular muscles includes various abnormalities ranging from isolated fibrosis of a single muscle to bilateral involvement of all extraocular muscles. Congenital unilateral orbital fibrosis is a specific fibrosis syndrome with only five cases previously reported. Although these reports postulated that a prenatal orbital inflammatory process caused the fibrosis, no etiology was proposed, nor was a mechanism suggested for entrance of the inflammation into the orbit. We discuss three additional cases in which evidence suggested prenatal orbital penetration. In one, a dense scar was found at birth from the skin of the upper lid to beyond the trochlea. The second had a dense fibrous tract extending from the upper lid skin to the trochlea and beyond into the orbit without a skin scar. These lesions could have been inflicted by the fetuses' own fingers or toes or, in the second case, by the twin fetus. The third had a benign mesenchymoma of the nasopharynx and skull that had eroded the medial orbital wall, which was seen on computed tomography scan but not on routine x-rays. The nature of the inflammatory substance is unknown. There was no other evidence of inflammation or infection in the eight reported cases. Possibly amniotic fluid itself, entering the orbit "late" in gestation, might cause this inflammation. We recommend that all children with congenital unilateral orbital fibrosis be examined specifically for defects in the orbit, and that computed tomography be employed rather than plain x-rays. PMID- 4040969 TI - Two calcium-sensitive spike after-hyperpolarizations in visceral sensory neurones of the rabbit. AB - Intracellular recordings were made from rabbit nodose neurones in vitro. Two temporally distinct spike after-hyperpolarizations (a.h.p.s) were identified in a subpopulation of C-type neurones. The fast a.h.p. after a single spike lasted no longer than 500 ms, while the slow a.h.p. persisted for seconds. Both a.h.p.s. were increased in amplitude in low K+ (0.56 mM) solutions and decreased in amplitude in high K+ (11.2 mM) solutions, and both were reversed at hyperpolarized membrane potentials. The slow a.h.p. was reduced in low Ca2+ (0.22 mM), in the presence of Ca2+ antagonists (Ni2+, 1 mM; Cd2+, 100 microM; or Co2+, 1 mM) and was enhanced in tetraethylammonium (5 mM). In approximately half of the cells tested, the fast a.h.p. was reduced in low Ca2+ and in the presence of the Ca2+ antagonists. In the remaining cells the fast a.h.p. was insensitive to these procedures. Prostaglandin (PGE1, 1-10 micrograms/ml) reduced the slow a.h.p. in all cells tested. Neither the Ca2+-sensitive nor the Ca2+-insensitive fast a.h.p. was affected by the prostaglandin. It is concluded that there is a subpopulation of C-type nodose neurones possessing a slow a.h.p. which is due to a Ca2+ dependent K+ current. This subpopulation of neurones can further be divided on the basis of the presence of a Ca2+-sensitive fast a.h.p. Furthermore, PGE1 pharmacologically separates the fast and slow a.h.p.s by selectively blocking the slow one. The blockage by the PGE1 is most probably not due to a reduction in Ca2+ influx. PMID- 4040970 TI - Hormones, behaviour and the menstrual cycle. AB - To date therefore, no consistent hormonal abnormality has been linked with premenstrual affective, physical or behavioural changes and, in turn, no consistent adverse behaviour has been positively linked with any particular menstrual cycle phase. At the same time, the proportion of actively menstruating women reported to identify premenstrual changes of a severity sufficient to warrant the illness label continues to fall so that a figure somewhere between 2 and 8% seems to be established where once figures in excess of 70% were claimed. The implication would seem to be that more thorough assessment of the relatively small number of women who are clearly identifiable as sufferers from cyclically mediated symptoms might well cast light on possible hormonal-behavioural links where larger, less careful studies of heterogeneous samples of women have failed to do so. The great majority of women appear to negotiate the premenstrual phase of their menstrual cycles with little or no impairment or difficulty. A small number appear to be vulnerable and the possibility that it is, at least in part, a biological vulnerability is hinted at in those reports which tentatively suggest that some women who are especially prone to post-partum 'blues' and who are particularly sensitive to oral contraceptives may be especially prone to premenstrual tension. Finally, the ubiquity of premenstrually perceived 'changes' as distinct from 'symptoms' raises the possibility that the extent to which a woman experiences various premenstrual changes as complaint or illness may depend 'more on her basic personality and the circumstances in which she experiences the cyclical changes than on the underlying cyclical mechanism'.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4040971 TI - Estrogen and progesterone receptors in the uterus of the vervet monkey. AB - Experimental conditions for the optimal measurement of estrogen (ER) and progesterone (PR) receptors in normal vervet monkey (Cercopithecus aethiops pygerythrus) uteri are described. The uteri of this primate were found to contain relatively high concentrations of both ER and PR. Levels of ER ranged from 151 to 822 femtomoles per mg protein (mean for group assayed is 327 +/- 165 femtomoles per mg protein). PR assays were performed on the same cytosols and the levels ranged from 444 to 2267 femtomoles per mg protein (mean of 1285 +/- 511 femtomoles per mg protein). Mean Kd values for the ER- and PR-ligand complexes were found to be 3.15 +/- 1.4 X 10(-10)M and 2.38 +/- 0.2 X 10(-9)M respectively, within the group analysed (n = 21). The ratio of PR to ER varied between 1.1 and 13.1 with a mean of 4.5 +/- 2.4. Ligand specificity studies revealed that [3H]-17 beta-estradiol binding to the ER could only be inhibited by estrogens or estrogen analogues. The PR however exhibited an affinity for a wider range of ligand types. In low ionic strength buffers both ER and PR sedimented as approximately 8S type molecules in the presence or absence of 10mM sodium molybdate. Both receptors dissociated into smaller components, following a short exposure to 0.4 M KCl and subsequent centrifugation in a gradient containing 0.4 M KCl. PMID- 4040972 TI - Observations on variability in LH release and fertility during oestrus in the domestic cat (Felis catus). AB - Hormonal changes, behaviour, ovulation and fertility were examined in response to coitus at two different times during oestrus in the female domestic cat housed in conditions of natural light (N = 13). On Day 2 or Day 4/5 of oestrus females were allowed 1 copulation in 15 min (single matings) or 2-3 copulations in 30 min (multiple matings). Plasma LH, oestradiol-17 beta and progesterone concentrations during the 24-h period after coitus were measured by radioimmunoassay; ovulation was assumed to have occurred if progesterone values were elevated 7-30 days after coitus. With the exception of 2 out of 3 animals receiving single matings on Day 2 of oestrus, all animals showed subsequent elevated progesterone values. Females receiving multiple matings had significantly greater releases of LH as measured by the area under the curve than those receiving single matings. There was significantly greater variability in the LH response of queens on Day 2 of oestrus compared to those on Day 4/5 for peak values and area under the curve; the only failure in release of LH was in queens on Day 2. Oestradiol levels did not differ significantly between Day 2 and Day 4/5 of oestrus. Progesterone values remained less than 1 ng/ml for 24 h after coitus. Both LH peak values and area under the curve were significantly greater for animals that became pregnant. There were also significant differences in coital behaviour between queens on Day 2 and those on Day 4/5 of oestrus.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4040973 TI - Comparison of the rate of decline in plasma progesterone concentrations at a natural and progesterone-synchronized oestrus and its effect on tonic LH secretion in the ewe. AB - The pattern of change in plasma progesterone and LH concentrations was monitored in Clun Forest ewes at a natural oestrus and compared to that observed after removal of progesterone implants. The rate of decline in plasma progesterone concentrations after implant withdrawal (1.8 +/- 0.2 ng/ml h-1) was significantly greater (P less than 0.001) than that observed at natural luteolysis (0.2 +/- 0.1 ng/ml h-1), and this resulted in an abnormal pattern of change in tonic LH secretion up to the time of the preovulatory LH surge. This more rapid rate of progesterone removal was also associated with a shortening of the intervals from the time that progesterone concentrations attained basal values to the onset of oestrus (P less than 0.05) and the onset of the preovulatory LH surge (P less than 0.01). However, there were no significant differences in the duration of the LH peak, preovulatory peak LH concentration, ovulation rate or the pattern of progesterone concentrations in the subsequent cycle. It is suggested that the abnormal patterns of change in progesterone and tonic LH concentrations may be one factor involved in the impairment of sperm transport and abnormal patterns of oestradiol secretion known to occur at a synchronized oestrus. PMID- 4040974 TI - Progesterone priming and age of ewe affect the life-span of corpora lutea induced in the seasonally anovulatory Merino ewe by the 'ram effect'. AB - Increasing doses of progesterone from 0 to 20 mg, given as a single i.m. injection, increased the proportion of corpora lutea that had a normal life-span when induced in ewes by the introduction of testosterone-treated wethers from 54% (19/35) to 100% (34/34). Injection of progesterone did not affect the induction of ovulation and 95% (130/136) of the anovulatory ewes ovulated. Nevertheless, a low proportion of ewes displayed oestrus between Days 16 and 26 after the introduction of testosterone-treated wethers (Exp. 1, 47%, 92/196; Exp. 2, 50%, 502/1000). Many of the ewes that did not display oestrus also failed to ovulate again (Exp. 1, 70%, 37/53). The proportions of anovulatory adult and maiden ewes that ovulated after the introduction of testosterone-treated wethers were not significantly different but significantly fewer maiden ewes were detected in oestrus. PMID- 4040975 TI - Internal and external determinants of the timing of puberty in the female. AB - A working hypothesis is proposed to account for the timing of puberty in female sheep. In the immature female, the frequency of LH pulses is low, and ovarian follicles do not develop to an advanced stage. During the pubertal transition, the frequency of LH pulses increases to drive follicular development and the production of oestradiol which evokes the gonadotrophin surge and ovulation. Central to the hypothesis is the hypothalamic pulse generator for GnRH that directs the pattern and level of LH secretion. Growth-related cues are monitored to regulate the activity of the GnRH pulse generator. When a sufficient body size is attained, the frequency of LH pulses increases both because the sensitivity to oestradiol inhibitory feedback decreases and because the GnRH pulse generator can be accelerated by the steroid. This increase in LH pulse frequency occurs provided the female has experienced the requisite exposure to photoperiod, i.e. the long days of summer followed by the short days of autumn. These photoperiodic cues are transduced by the pineal gland into a humoral signal which is an increased nocturnal production of melatonin. Failure to grow to the appropriate body size or to experience the appropriate exposure to photoperiod leads to a maintenance of the prepubertal anovulatory condition because the GnRH pulse generator operates at low frequency. PMID- 4040976 TI - Epidemiologic study of carcinoma in situ of the cervix. AB - From 1950 to 1979, 1,248 cases of cancer in situ were treated in the Department of Gynecology, Cancer Institute Hospital, Tokyo. Detailed data were obtained from 585 of the patients by interview. Many patients had had their first sexual experience at an early age. Many had had more than two sexual partners, and there was a large discrepancy between the age at first sexual intercourse and at first marriage. The above factors seem to be related to the development of cancer in situ. PMID- 4040977 TI - Potential neuroleptic agents. 3. Chemistry and antidopaminergic properties of substituted 6-methoxysalicylamides. AB - A series of substituted 6-methoxysalicylamides were synthesized from their corresponding 2,6-dimethoxybenzamides by demethylation of one methoxy group with boron tribromide. Substituted 6-methoxysalicylamides having a lipophilic aromatic substituent in the 3-position para with respect to the methoxy group, e.g. a bromo or an iodo atom or an ethyl or a propyl group, and having an (S)-N-(1-alkyl 2-pyrrolidinyl)methyl moiety as the side chain were found to be potent blockers of [3H]spiperone binding in vitro and potent inhibitors of the apomorphine syndrome in the rat. Similar to remoxipride but in contrast to haloperidol, some of the substituted salicylamides show a 10-20-fold separation between the dose that inhibits hyperactivity and that which inhibits stereotypy. It was concluded that, besides the requirement of a lipophilic substituent in the position para to the methoxy group for antidopamine activity in vivo, the formation of a coplanar six-membered pseudoring involving the amide moiety and the methoxy group is a structural requirement for activity in vitro. PMID- 4040978 TI - Treatment of hypertrophic cardiomyopathy: relation to pathological mechanisms. AB - In patients with hypertrophic cardiomyopathy, clinical symptoms such as exertional dyspnea, angina and collapse are considered to be rather the consequence of diastolic than of systolic dysfunction of the left ventricle. Beta blocker therapy is aimed at reducing systolic overcontraction while calcium blockers predominantly therapy is aimed at reducing systolic overcontraction while calcium blockers predominantly improve diastolic filling characteristics. Therefore 61 consecutive patients with well defined hypertrophic cardiomyopathy were treated with calcium channel blockers: 60 patients with verapamil at average dose 530 mg (320 to 720 mg/d) and one patient received 30 mg nifedipine. All patients had clinical, noninvasive and cardiac catheterization evaluation at the time of entry into the study. Therapy was continued for an average of 54 months (10 to 96). Follow-up studies were performed at 6-month intervals. Subjective improvement was achieved in 47 of 55 symptomatic patients (85%). Heart size, judged as heart volume from tele-chest X-ray in supine position, showed a reduction in 36/61, no change in 15/61 and increase in 10/61. On average in all 61 patients, a significant reduction from 947 to 833 ml/1.73 m2 was seen. Twenty six patients who had been followed for an average of 24 months prior to verapamil therapy on beta blockers or no treatment had heart volume increases averaging 12% in the pre-verapamil period. Electrocardiography (ECG) showed a significant reduction in QRS amplitude and a tendency towards normalization of ST/T segments. Serial echocardiography study showed small but significant reduction in left atrial diameter. Repeat catheterization was performed in 19 patients and a significant reduction in intraventricular pressure gradient, left ventricular muscle mass and coronary artery diameter was demonstrated. Three patients died during the study (256 patient-treatment-years) for an annual mortality rate of 1.3%. This mortality is considerably lower than reported for patients receiving no treatment, beta-blockade, or surgery. Of all 61 patients only one had surgery related to the hypertrophic cardiomyopathy. One patient had the dose of verapamil reduced because of the occurrence of heart block. No patient discontinued the drug because of side-effects. Utilizing serial noninvasive and invasive studies, we conclude that verapamil therapy in hypertrophic cardiomyopathy results in objective and subjective improvement, a low death rate and little need for operation as compared to standard therapy. PMID- 4040979 TI - Incompetent urethral sphincter in a girl with a unilateral single ectopic ureter. AB - A rare case of an incompetent urethral sphincter associated with a unilateral single ectopic ureter is reported. Urinary incontinence persisted even after removal of a dysplastic kidney draining into the vagina. No neurological defect was found. Manual compression of the bladder elicited urine leakage from the urethra, and the urethral closure pressure was markedly low. Cystometry and voiding cystourethrography were normal. Continence was restored completely by a urethral sling operation. PMID- 4040981 TI - Relative urethral leakage pressure versus maximum urethral closure pressure. The reliability of the measurement of urethral competence with the new tube-foil sleeve catheter in patients. AB - In 78 female patients the urethral leakage pressure, defined as the intravesical pressure at which leakage starts from the urethral orifice, was estimated with the tube-foil sleeve catheter. In accordance with the definition of maximum urethral closure pressure, the relative urethral leakage pressure was defined as urethral leakage pressure minus intravesical resting pressure. In the same patients urethral closure pressure was also measured by urethral pressure profilometry with a flexible micro pressure-sensor catheter. On the average the ratio of relative urethral leakage pressure/urethral closure pressure was about 0.5. Relative urethral leakage pressure and urethral closure pressure were higher than the maximum detrusor pressure increases during detrusor instabilities in 21 continent patients with motor urge. The relative urethral leakage pressure correlated better with the detrusor pressure elevations at which fluid loss from the urethral orifice started in 24 motor urge incontinent patients than urethral closure pressure did. PMID- 4040980 TI - Transvaginal closure of the bladder neck and placement of a suprapubic catheter for destroyed urethra after long-term indwelling catheterization. AB - We report on 6 women with continuous urinary incontinence as a late complication of an indwelling urethral catheter for neurogenic bladder. Pressure necrosis by the balloon resulted in progressive destruction of the entire urethra, with subsequent incontinence despite the catheter. Surgical attempts at bladder neck closure to correct the incontinence generally have been unsuccessful. Instead of supravesical urinary diversion, we performed transvaginal closure of the bladder neck and percutaneous placement of a permanent suprapubic tube cystostomy. All 6 patients remained dry after closure and none has shown upper urinary tract deterioration at followup for as long as 5 years. PMID- 4040982 TI - Urethral instability: related to stress and/or urge incontinence? AB - Urethral instability (pressure variations of more than 15 cm. water during bladder filling) was noted in 12 of 34 women with bladder instability and 13 of 139 with a stable bladder. Of the patients 10 had urge, 5 mixed and 8 genuine stress incontinence, while 1 had enuresis and 1 had recurrent cystitis. A clear correlation between urethral pressure variations and electromyographic fluctuations in the anal and/or urethral sphincter was found in 14 of 17 patients. Only urethral pressure variations of more than 35 cm. water are reported as provoking urgency. Different types of pressure fluctuations are described but no fundamental differences or causative factors were found. A nervous rather than a vascular factor is designated as the main cause for urethral instability. PMID- 4040983 TI - Mortality of northern fur seal pups in relation to growth and birth weights. PMID- 4040984 TI - Idiopathic apical left ventricular aneurysm in hypertrophic cardiomyopathy. Report of 3 cases, and review of the literature. AB - In a review of 160 cases of hypertrophic cardiomyopathy which underwent hemodynamic studies, 3 cases of apical aneurysm of the left ventricle of unidentifiable etiology were found. Bearing in mind the rarity of apical idiopathic left ventricular aneurysms, the authors believe this association with hypertrophic cardiomyopathy is of some interest and point out the possible pathogenetic mechanisms. PMID- 4040985 TI - [Mitoxantrone in the treatment of relapsed and refractory malignant lymphoma]. AB - Mitoxantrone is an anthracenedione with structural similarities to adriamycin but without the amino-sugar moiety on the parent molecule. The compound attracted attention on the basis of animal tumor studies in which it showed equal or superior efficacy compared to adriamycin, but with diminished cardiotoxicity; and it was not fully cross-resistant to adriamycin. Our in vitro studies using human small cell lung cancer cell line (SBC-3) disclosed the absence of cross resistance between mitoxantrone and adriamycin: SBC-3/ADM, which had developed resistance by continuous exposure to increasing concentration of adriamycin, was as equally sensitive to mitoxantrone as SBC-3 was when tested by clonogenic assay. A phase II study conducted in our Department revealed that mitoxantrone was active to malignant lymphoma refractory to conventional agents including adriamycin: 6 (33%) of 18 patients responded to the agent. Based on the results of our phase II studies of mitoxantrone, etoposide, and cisplatin in malignant lymphoma, we have conducted a phase III study of a 4-drug combination of these 3 drugs plus prednisolone in relapsed or refractory lymphoma: Out of 14 patients, 3 responded completely and 4 did partially, so far. The regimen would appear useful as a salvage therapy for refractory lymphoma. PMID- 4040986 TI - [Collaborative phase II study of etoposide (NK-171). Urological Cooperative Study Group of etoposide (NK-171)]. AB - Phase II study of Etoposide administered intravenously and orally was performed in 163 patients with urologic malignancies for the clinical evaluation of responses and adverse effects. The eligibility of the patients and evaluation of the responses were carried out according to the general criteria proposed by Koyama and Saito. Out of the 163 patients registered in the study, it was possible to evaluate 141. In the cases of intravenous administration, the response rates were 16.7% in testicular cancer mostly refractory to prior therapy, 15.6% in bladder cancer, 7.7% in prostatic cancer, and 0% in renal cell route. The overall response rate was 11.1%. Toxicities were noted in the gastrointestinal tract, the rates being 54.4% for anorexia, 35.4% for nausea and 17.7% for vomiting. Alopecia was observed at a high incidence of 72.1%. Myelosuppression leukopenia and thrombocytopenia were the other prominent adverse effects. PMID- 4040987 TI - [Interaction of cytoskeleton and cell membrane]. PMID- 4040988 TI - [A case with complete remission of local recurrence of ureteral tumor after cis diamminedichloroplatinum (CDDP) and radiation]. PMID- 4040989 TI - [Combined therapy of bladder cancer]. PMID- 4040990 TI - [A microscope coupled with an argon laser for microsurgery of retinal detachment]. PMID- 4040991 TI - Study of fetal organ growth in Wistar rats from day 17 to 21. AB - A total of 1633 Wistar rat fetuses was used to determine weights of the fetus and several fetal organs on days 17 to 21 of gestation. Heart, lung, liver, kidney, stomach, intestine, brain, femur, thyroid and adrenal weights were recorded. Growth curves of the whole body and organs were calculated. A linear semi-log relationship between organ weight and day of gestation was shown. The doubling weight times were 1.5 days for whole bodies and for organs they ranged between 0.9 (spleen) and 3.4 (adrenals) days. A correlation between the rate of organ growth and the start of the organ function was observed. PMID- 4040992 TI - A continuum model for surface contraction waves. AB - The periodic travelling waves which appear on some animal eggs after fertilization are considered here. These are thought to be caused by a calcium initiated calcium release on the surface, causing calcium waves. A continuum model is developed where the cell is treated as a small viscous droplet with a surface contamination. When a periodic source of surfactant acts at one pole and propagates down the cell surface to the opposite pole, the drop responds by forming constriction rings which move from pole to pole. PMID- 4040993 TI - Diurnal profiles of plasma cholecystokinin (CCK) and vasoactive intestinal polypeptide (VIP) in man. PMID- 4040994 TI - [Essential thromboembolism: study of 9 cases]. PMID- 4040995 TI - [Severe thrombocytopenia and intravenous heroin]. PMID- 4040996 TI - [Thrombocytopenia and methadone]. PMID- 4040997 TI - [Flattening of hypertrophic scars by punctiform argon ion laser coagulation in several sessions]. AB - 11 hypertrophic scars were treated by different argon ion laser techniques. The observation period is 0.5-3 years. Punctiform coagulation zones of 2-3 mm diameter, interspersed by untreated areas of scar tissue of 2 mm length, which are by lasered 6 weeks later in a second laser session, has proved most successful. Laser sessions are repeated in this manner until sufficient flattening of the hypertrophic scar is achieved. A low power density and very brief multiple interrupted radiation periods for controlling the thermal effect are useful. It is assumed that small superficial coagulation necroses produced by the argon ion laser will result in subsequent scar tissue being formed in other directions while decreasing the collagen formation, eventually resulting in flattening of the hypertrophic scar. PMID- 4040998 TI - Adenylate cyclase activity and motor behavior following cerebral ischemia in the unanesthetized gerbil. AB - Five minutes of bilateral carotid occlusion in unanesthetized gerbils produced substantial changes in spontaneous locomotor activity. Behavior was decreased after 1 hr of reperfusion and was increased at 24 hrs post-ischemia. Adenylate cyclase activity was measured in homogenates of frontal cortex and hippocampus at 90 min and 24 hrs following 5 min of cerebral ischemia. Enzyme activity was determined in the absence and presence of the activators guanosine-5' triphosphate (GTP), guanylyl-5'-imidodiphosphate (GppNHp), isoproterenol (Iso) plus GTP, and forskolin (Fors) plus GTP. Homogenates responded with expected increases over basal adenylate cyclase activity with addition of all activators. An additional small increase in isoproterenol-stimulated activity was observed in frontal cortex homogenates at 90 min post-ischemia. No other significant changes in adenylate cyclase activity were observed after either 90 min or 24 hrs of reperfusion. The substantial increases in locomotor activity evident at 24 hrs after transient ischemia are not associated with measurable changes in adenylate cyclase activity in homogenates of frontal cortex or hippocampus. PMID- 4040999 TI - Pharmacological alleviation of cholinergic lesion induced memory deficits in rats. AB - The cholinergic cells of the nucleus basalis of Meynert (nbM) have recently been found to degenerate in Alzheimer's disease and are thought to be at least partly responsible for the cognitive deficits which are characteristic of this disease. These experiments explored the behavioral effects of bilateral excitotoxic lesions of the nbM in adult rats. The first experiment showed that nbM lesions lead to a substantial deficit in the 24 hour retention of the habituation to a novel environment without affecting general exploratory behavior. The second experiment showed that this retention deficit is a general phenomenon reflected in the 72 hour retention of a one trial passive avoidance task. These retention deficits could be reversed by the postacquisition administration of the acetylcholinesterase inhibitor, physostigmine. These results support the hypothesis that central cholinergic systems are involved in the retention of learned responses, and suggest that cholinergic lesion induced retention deficits can be reversed by pharmacological means. PMID- 4041001 TI - Purification of a cell growth inhibitor from bovine cerebral cortex cells. AB - A glycopeptide, isolated from bovine cerebral cortex cells and added in only nanogram levels to cells in culture, has been shown to inhibit both cell protein synthesis and cell division. When purified by gel filtration and Ulex europaeus lectin affinity chromatography, the radioiodinated preparation was subjected to high resolution isoelectric focusing and shown to contain three species of macromolecules. The glycopeptide focusing at pH 8.1 comprised over 75% of the radioiodinated material and possessed inhibitory activity against both cell protein synthesis and cell division. A second species that focused at pH 8.3 was also found to be inhibitory to cell metabolism and may have represented a variant of the major glycopeptide. PMID- 4041000 TI - Sensitization to stress: the enduring effects of prior stress on amphetamine induced rotational behavior. AB - In rats with a unilateral 6-OHDA lesion of the substantia nigra exposure to footshock or immobilization stress produced a long-lasting enhancement in the rotational behavior evoked by a subsequent injection of amphetamine. However, the effect was dependent on the environmental context in which stress was applied. It is suggested that stress may induce enduring changes in brain and behavior similar to those produced by psychomotor stimulant drugs. PMID- 4041002 TI - Rapid induction of supersensitivity to muscarinic antagonists-induced motor excitation by continuous stimulation of cholinergic receptors. AB - Following single or repeated treatment with the irreversible anticholinesterase, DFP or, during infusion of the muscarinic receptor agonist, oxotremorine, and the reversible anticholinesterase physostigmine, effects of challenges with muscarinic antagonists were studied in rats. The antagonists, atropine, scopolamine, benztropine, orphenadrine and trihexyphenidyl induced, to a low degree, limb-shakes (myoclonus) and stereotyped behaviors in normal rats. However, within 24-72 hr after the above pretreatments, this myoclonus was significantly enhanced. The anticholinergic-stereotypies were also increased but only by severe cholinergic pretreatment and at a time later than that for the myoclonus. Myoclonus and stereotypies are known to be produced by treatments which directly enhance serotonergic and dopaminergic activities, respectively. It is suggested that during prolonged cholinergic stimulation, the cholinergic monoaminergic balance in the brain can be altered depending upon the degree of stimulation. This could be responsible for the observed differential onset of changes in the anticholinergic-behavioral responses, which could, in turn, be mediated by different monoaminergic (serotonin and dopamine) systems. PMID- 4041003 TI - Sterol carrier protein. PMID- 4041004 TI - Chronic alcohol ingestion alters the calcium permeability of sarcoplasmic reticulum of rat skeletal muscle. AB - Heavy sarcoplasmic reticulum (SR) was prepared from skeletal muscle of control and chronic alcoholic rats, and the effect of in vitro addition of ethanol on the passive Ca2+ permeability was studied. The SR was loaded with Ca2+ in the absence of ATP. Then efflux was initiated by adding an EGTA solution to decrease the extravesicular Ca2+ concentration. The decrease of Ca2+ content of the SR was measured by an optical method using an encapsulated metallochromic indicator (calcein). The Ca2+ permeability of alcoholic rat SR was higher than that of control rats, especially at low external Ca2+ concentrations (below 1 microM). An in vitro (acute) exposure of SR to ethanol increased the Ca2+ permeability of the SR. However, the degree of increase in alcoholic rat SR was smaller than that in control rat SR. PMID- 4041005 TI - Sarcoplasmic reticulum membrane of rat skeletal muscle is disordered with chronic alcohol ingestion. AB - Heavy sarcoplasmic reticulum (SR) was prepared from skeletal muscle of chronic alcoholic rats and control rats. Compared with control rat SR, the SR prepared from alcoholic rats is leakier to Ca2+ and has a lower level of maximum storable Ca2+. With in vitro exposure to ethanol, the Ca2+ release of alcoholic rat SR was not enhanced as much as that of SR prepared from control rats. By using the spin probes 5-, 7-, 12-, and 16-doxylstearic acid, the disordering effect of ethanol on the SR membrane was studied. The results suggest that SR membrane of chronic alcoholic rats is less ordered than that of control rats even in the absence of in vitro ethanol. However, chronic SR membrane shows a greater resistance to the disordering effect of in vitro addition of ethanol than control rat SR. PMID- 4041006 TI - Crosslinking of chromosomal antigen common in human tumors to DNA by cis diamminedichloroplatinum (II). AB - The antisera specific for dehistonized HeLa cell chromatin were obtained by injecting rabbits or goats. Treatment of chromatin with cis-DDP crosslinked the active proteins to DNA thus preventing dissociation of the proteins in a high salt environment. Immunochemical staining of electrophoretically separated chromosomal proteins transferred to nitrocellulose sheets revealed that cis-DDP among others crosslinked the protein with m.w. of about 81 000. This protein is the only major protein antigen presented in several human tumors and absent in normal human tissues. PMID- 4041007 TI - Rapid induction of selective transcription by auxins. AB - Nuclei isolated from excised soybean plumules that were treated with 2,4 dichlorophenoxyacetic acid (2,4-D) were active in transcription of four auxin regulated genes or DNA sequences, which have been described previously (G. Hagen, A. Kleinschmidt, and T. Guilfoyle, Planta 162:147-153, 1984). The rates of transcription of the auxin-responsive sequences were 10- to 100-fold greater with nuclei isolated from auxin-treated plumules than with those from untreated plumules. The transcriptional response was also observed with hypocotyls of intact soybean seedlings and hypocotyl sections, as well as with green bean and mung bean plumules that were treated with 2,4-D. Other auxins, including 2,4,5 trichlorophenoxyacetic acid, alpha-naphthaleneacetic acid, and indole-3-acetic acid, also induced the transcriptional response. Increased transcription rates were observed within 5 min after application of auxins to excised plumules, and half-maximal to maximal transcription rates were achieved by 15 min after application of auxins. As little as 10(-7) to 10(-8) M 2,4-D induced a transcriptional response, but maximal transcription rates were achieved at 10(-3) M 2,4-D. Brief treatment with the protein synthesis inhibitor cycloheximide did not inhibit the induction of transcription by auxins. These results clearly demonstrated that auxin-regulated gene expression is under rapid transcriptional control. PMID- 4041008 TI - Echovirus encephalitis/myositis in X-linked agammaglobulinemia. PMID- 4041009 TI - Dawn phenomenon in IDDM. PMID- 4041010 TI - The mycotoxicological chain and contamination of food by ochratoxin A in the nephropathic and non-nephropathic areas in Yugoslavia. AB - Research was carried out on the distribution of moulds on cereals in vegetation and in storerooms in the period from 1974 to 1981 and on ochratoxin (OA) in stored maize and wheat as well as residues of OA in the organs of swine in the nephropathic and non-nephropathic areas in the SR of Croatia, Yugoslavia. It was shown that moulds belonging to toxogenic species contaminate cereals in vegetation to an approximately equal degree in both areas (Penicillium 6.6-20.0%, Aspergillus 2.5-6.6% and Fusarium 80-100%). Stored cereals were contaminated by species of Penicillium 75-82.8%, Aspergillus 2.5-27.1% and Fusarium 57.1-82.5%, with a somewhat higher degree of contamination in the nephropathic area. Ochratoxin A occurs on cereals on the whole territory of the SR of Croatia, but average concentrations are higher in the nephropathic area (45% of the positive findings of OA were over 2 mg/kg). Residues of OA in the kidneys (16-77 micrograms/kg), liver (0-21 micrograms/kg) and blood (36-77 micrograms/l) were detected in 38 organs taken from swine in the nephropathic area, but this toxin was not found in the 6 samples taken from the non-nephropathic area. In the same organs histopathological changes were found in the kidneys (interstitial nephritis with parenchymal degeneration of the distal parts of the tubular epithel) and liver (interstitial hepatitis with fatty degeneration of the liver). PMID- 4041011 TI - Splitting hairs and other intermediate filaments. PMID- 4041012 TI - Control of eukaryotic messenger RNA synthesis by sequence-specific DNA-binding proteins. AB - The enzymatic machinery that carries out RNA synthesis provides the cell with the means to adjust the patterns of transcription in response to environmental and developmental signals. In eukaryotes, this regulation is mediated in part by promoter-specific transcription factors, which are DNA-binding proteins with the ability to discriminate between distinctive DNA sequence elements found in the promoter regions of different genes. The presence of these factors bound to DNA enables other components of the transcriptional machinery, including the RNA polymerase, to initiate transcription with selectivity and accuracy. PMID- 4041013 TI - The health care professional's role in occurrence of cerebral palsy. PMID- 4041014 TI - Nebraska stillborn survey--1981. PMID- 4041015 TI - Lack of effect of GABA on [3H]leucine incorporation into a rat oviduct ribosomal system. AB - A ribosomal system for [3H]leucine incorporation was isolated from the rat oviduct in order to study the possible effect of GABA on [3H]leucine incorporation during the estrous cycle. The system showed an absolute requirement for Mg2+ and about 50% dependence on an energy source. Optimal [3H]leucine incorporation occurred under 3-6 mM Mg2+ and 100 mM K+ and was higher in diestrous-1 than in estrous or proestrous. GABA (10 mM) had no effect on [3H]leucine incorporation in any of the three estrous phases studied. PMID- 4041016 TI - Pathogenesis of mouse scrapie: dynamics of vacuolation in brain and spinal cord after intraperitoneal infection. AB - At the late clinical stage of scrapie in mice, the severity and distribution of vacuolation in the brain (the lesion profile) is largely determined by the strain of agent and the genotype of the mouse: under controlled conditions, lesion profiles can be used to distinguish between scrapie strains. This paper describes the sequential development of lesions in brain at much earlier times and includes a study of spinal cord. Mice (CW) were infected intraperitoneally with 139A scrapie. Grey matter vacuolation first occurred in thoracic cord, developing later in lumbar and cervical cords, and then in various brain regions in a caudal to rostral sequence. This pattern closely matches the sequential spread of infection from mid-thoracic cord to much of the CNS that was previously found in this scrapie model. Further studies of grey matter in spinal cord suggest that agent entered the mid-thoracic region via sympathetic fibres. Vacuolation in white matter mirrored the grey matter pattern within an area but always occurred later. The severity of grey matter vacuolation in the four areas of the CNS where it developed early, reached plateau levels before the clinical stage of scrapie, but the severity was still increasing at the clinical stage in areas where vacuolation had started late. Hence the severity of lesions in a particular area may sometimes be limited by the time available for them to develop before the host dies. It appears that the distribution of vacuolation in this particular scrapie model is initially influenced by that of the infectious agent and only later does it reflect the distribution of vacuolation target areas shown by the characteristic lesion profile. PMID- 4041017 TI - Mechanisms underlying hypertensive reactions under emotional stress. AB - In experiments on alert cats shifts of the systemic hemodynamics under emotional stress were studied. The hypertension caused by confrontation with a dog is shown in most cases to be attended by suppression of the baroreceptor reflexes. Hypertension does not develop in these animals after section of the sinocarotid and aortic nerves. In 2 cats the baroreceptor reflexes did not change under emotional stress and deafferentation of the carotid sinuses and arch of the aorta intensified hypertension upon confrontation with a dog. It is concluded that diverse mechanisms lead to hypertension under emotional stress in different animals. PMID- 4041018 TI - [Breast carcinoma concurrent with pregnancy]. PMID- 4041019 TI - Suckling decreases dopamine turnover in both medial and lateral aspects of the median eminence in the rat. AB - The effect of suckling on dopamine (DA) turnover was studied in the medial and lateral aspects of the median eminence. In 10-day postpartum lactating rats suckling decreased DA turnover 2.2-fold in the medial and 2.1-fold in the lateral median eminence. Norepinephrine turnover did not differ in suckled and non suckled rats. These results are consistent with the hypothesis that decreased DA release is a component of the neuroendocrine reflex mediating suckling-induced prolactin release. The results further indicate that dopaminergic neurons distributing to both medial and lateral aspects of the median eminence are involved in the suckling response. PMID- 4041020 TI - D-Amino acids influence ultrasonic calling in mice pups: effects of D phenylalanine and D-leucine. AB - 6-day-old mice pups were injected with D-amino acids (D-phenyl-alanine + D leucine), and their ultrasonic distress vocalizations were measured. D-Amino acids, which exert opioid-like effects, reduce the number of ultrasonic calls without affecting the activity of the pups. This effect is reversed by naloxone, an opioid antagonist. The role of endogenous opioids in modulating early attachment is discussed. PMID- 4041022 TI - Treating violence. PMID- 4041021 TI - Diurnal variations in electroconvulsive shock-induced seizures: involvement of endogenous opioids. AB - Electroconvulsive shock (ECS)-induced seizures present a clear cut diurnal rhythmicity when BALB/c mice are subjected to a light-dark (L/D) schedule. On the contrary, in the absence of external synchronizers no evident fluctuations in epileptic behaviour were evident. Naloxone decreased the threshold of ECS-induced convulsions, thus confirming an involvement of opioids in this type of behaviour. These findings indicate that opioids present a diurnal (L/D) but not circadian (L/L) rhythmicity in BALB/c mice. PMID- 4041023 TI - The potential role of blowflies in the transmission of taeniid tapeworm eggs. AB - In laboratory studies with 3 species of Calliphora more than half were shown to ingest eggs of Taenia hydatigena from the surface of dog faeces with a maximum of over 5000 eggs in 1 fly. Most eggs were voided within 48 h and between 38 and 48% of these eggs had lost their embryophores. In field studies carried out in the South Island of New Zealand, traps baited with dog faeces captured the following blowfly species in decreasing order of abundance: Hybopygia varia, Calliphora quadrimaculata, C. hortona and C. stygia. Peak numbers were trapped in January, February and March. Almost 25% of wild flies, caught after feeding for up to 3 min on dog faeces naturally contaminated with taeniid eggs, had eggs in their intestine. When administered to lambs all 4 species of fly transferred infection. Lambs grazed in winter on plots near kennels that had housed dogs with patent infections of T. hydatigena acquired higher worm burdens than those grazed further away. The burdens were greater downwind of the prevailing wind. After removal of the dogs, blowflies caught in the vicinity contained taeniid eggs but the contents of pitfall traps did not. Blowflies, and to a much lesser degree the insects and dust caught on sticky traps during the presence of the dogs, transferred infection when administered to naive lambs. PMID- 4041024 TI - [Effect of enkephalins on the activity of stress hormones in acute myocardial infarct]. PMID- 4041026 TI - [Model for studying the effect of intrauterine synechiae on the estrous cycle]. PMID- 4041025 TI - [Delayed hypersensitivity reaction and natural cellular immunity. A comparative study of the effectiveness of different immunomodulators]. PMID- 4041027 TI - [Prevention of heart contractile function disorders in myocardial infarct by preliminary adaptation to brief stress exposures]. PMID- 4041028 TI - Immobility experiments with dogs of the Arkansas Line of Nervous Pointers. AB - As demonstrated in four experiments, dogs and pups of the Arkansas Line of Nervous Pointers, in contrast to kennel-mate dogs of the normal line, respond to manual inversion and brief restraint in an open sling with prolonged, mainly hypertonic, immobility. This response is consistent and replicable. At least in 4 month-old pups, the duration of sling immobility is positively correlated with the degree of behavioral pathology as determined by the objective Human Interaction Test. We found no evidence of basic difference between upright freezing and supine immobility. PMID- 4041029 TI - Impaired renal acidification in infants with fetal alcohol syndrome. AB - Urinary acidification was studied in six unrelated infants with fetal alcohol syndrome and eight healthy age-matched infants. Creatinine clearance, fractional sodium excretion, plasma renin activity, and plasma aldosterone were normal in all patients but fractional potassium excretion was lower in the patients than in the controls (p = 0.0001). After ammonium chloride loading, minimum urine pH was significantly higher in FAS patients than in control subjects (5.5 +/- 0.1 and 4.7 +/- 0.1, respectively, p = 0.00005). Net acid excretion was also lower in the patients (24.5 +/- 1.7 Eq/min) than in the controls (27.8 +/- 2.1 Eq/min, p = 0.008). Following sodium bicarbonate loading, fractional bicarbonate excretion was significantly higher (p = 0.00005) and fractional potassium excretion significantly lower (p = 0.002) in the patients than in the controls with comparable blood pH and bicarbonate levels. Treatment with chlorothiazide lowered plasma potassium and raised plasma bicarbonate to normal levels (p = 0.05). Concomitantly, fractional sodium excretion, fractional potassium excretion, and urinary net acid excretion increased significantly (p = 0.01). We conclude that patients with fetal alcohol syndrome have a defect in distal acidification and potassium excretion which cannot be attributed to abnormal aldosterone secretion. PMID- 4041030 TI - [Congenital spherocytosis in children with particular reference to the neonatal period]. PMID- 4041031 TI - Aicardi syndrome in one dizygotic twin. AB - The Aicardi syndrome consists of infantile spasms, defects of the corpus callosum, dorsal vertebral anomalies, and chorioretinal lacunar defects. The etiology is, as yet, unknown. The most likely cause, however, is an X-linked mutational event that is lethal in males. The first case of the Aicardi syndrome known to occur in one twin is reported. The patient was female and her unaffected sibling was male. This provides strong evidence to support the theory of an X linked mutational event as the cause of this condition. The typical chorioretinal defects, often difficult to document because these children die at an early age, are clearly illustrated in this report. PMID- 4041032 TI - [Dynamics of the composition of lipids in human milk during lactation]. AB - The authors have studied the total lipids, triglycerides and cholesterol in the milk of 30 mothers over a lactation period of 4 days to 10 months. The total lipids showed diurnal oscillations with a minimal level in the morning and maximal level (P less than 0.001) at 1 p.m. and a slight decrease in the evening, without reaching the levels found in the morning. The lipid concentration in the milk decreases after 4 months of lactation. The oscillations of the lipids take place on the expense of the triglyceride content (r = 0.99). Cholesterol represented on the average 1.54% of the lipid content, showed a maximum level at a month and decreased after 6 months of lactation. The dynamics of lipid composition of the human milk suggests a physiologic significance in the development of the infant. PMID- 4041033 TI - An anonymous single-copy X-chromosome RFLP for DXS72 from Xq13-Xq22 [HGM8 provisional no. DXS72]. PMID- 4041034 TI - Vasopressin does not enhance memory processes: a study in human twins. AB - Behavioral effects of lysin-vasopressin (LVP) were investigated applying two paradigms from human experimental psychology. The first task was designed to simulate amnesic symptoms in normals. The second task addressed the emotional value of the items to be processed. Additionally, EEG recordings were used as indicators of the central nervous system effectiveness of LVP. Blood pressure and heart rate measured peripheral arousal. The co-twin control method was employed to increase experimental power. Contrary to the prediction of the vasopressin memory hypothesis none of the specific memory parameters was improved by LVP treatment. Changes in the electrical activity of the brain, but not in blood pressure and heart rate indicated central nervous system actions of LVP. However, interpretation of LVP effects in terms of memory processing seems not to be justified. PMID- 4041035 TI - UV suppression of mast cell-mediated wealing in human skin. AB - Prior exposure of normal skin to subthreshold doses of UVR from a "UVA" phototherapy cabinet resulted in a small but significant reduction of the wealing response to intradermally injected codeine phosphate, a mast cell degranulating agent. The flare component of the reaction was not affected, nor were the responses to intradermally injected histamine. Both UVA and UVB from banks of filtered fluorescent tubes appeared to produce a similar but less pronounced effect. Dose-response studies revealed that the inhibition of mast cell-mediated wealing required a certain cumulative threshold dose of UVR (about 35 J/cm2 UVA + 20 mJ/cm2 UVB). The observed reduction in wealing could not be entirely explained by differences in the content of tissue histamine. It is concluded that repeated exposure to a broad range of UV wavelengths can depress the response of mast cells in vivo to degranulating agents by an unknown mechanism. This finding may have relevance to some of the observed therapeutic effects of phototherapy in certain inflammatory dermatoses and especially cutaneous mast cell disorders. PMID- 4041036 TI - The cholinergic influences on aggression in isolated mice. AB - The influence of cholinomimetics and cholinolytics on the isolation-induced aggression in mice was examined. Arecoline, bethanechol, carbachol, oxotremorine, pilocarpine, and physostigmine were found to potentiate aggression, while cholinolytics - atropine and scopolamine - suppressed aggressive behavior. Cholinolytics with no central action did not inhibit aggression. The results indicate that in addition to catecholamines also the cholinergic system may participate in the behavioral model under examination. PMID- 4041037 TI - The central action of carbamazepine as a potential antidepressant drug. AB - Carbamazepine (CBZ) was studied in mice and rats with regard to its antidepressant activity. CBZ did not counteract hypothermia and ptosis induced by reserpine, hypothermia evoked by apomorphine, or sedation and hypothermia induced by clonidine. CBZ shortened the immobility time in the behavioral despair test in rats (but not in mice). It attenuated hyperactivity evoked by d-amphetamine, not affecting stereotypy induced by that drug. CBZ inhibited head twitches evoked by 5-HTP, as well as the hind limb flexor reflex of the spinal rat, having no effect on its stimulation by noradrenaline and 5-hydroxytryptamine agonists. CBZ administered repeatedly did not enhance clonidine aggressiveness or d-amphetamine locomotor hyperactivity, acting differently than many antidepressant drugs. The obtained results indicate that CBZ is not similar in its action to typical and many atypical antidepressants. PMID- 4041038 TI - The short child. A matter of time or cause for concern? AB - Short stature is less likely to have an endocrine basis than is commonly thought. Any of a number of chronic systemic diseases can slow growth, short stature may result from a genetic tendency or disorder, growth may be constitutionally delayed, or it may be retarded by intrauterine influences. True endocrine causes include thyroid or adrenal disorder, growth hormone deficiency, and psychosocial dwarfism. Although growth hormone deficiency is quite rare, it has received increased attention recently. The capability to produce human growth hormone by recombinant DNA techniques presents the prospect that replacement therapy will be more readily available to those patients who might benefit from it. Caution is called for, however, in making use of this agent for patients other than those with proven growth hormone deficiency. PMID- 4041039 TI - Mediastinal zygomycosis. AB - A young girl with pulmonary zygomycosis involving the mediastinum and presenting as superior vena caval obstruction is reported. Mediastinal involvement due to zygomycosis is a rare occurrence. PMID- 4041040 TI - Primary nongestational choriocarcinoma of the ovary. AB - Primary choriocarcinoma of the ovary arising, presumably, from a germ cell is extremely rare. The patient, a 16 year old girl who presented with dysuria and frequency of micturition developed fatal haemoperitoneum due to rupture of a pure primary nongestational ovarian choriocarcinoma. PMID- 4041041 TI - EORTC Genitourinary Group Monograph 2, Part A: Therapeutic principles in metastatic prostatic cancer. Proceedings of a symposium held in Rotterdam, The Netherlands, September 14 and 15, 1984. PMID- 4041042 TI - Selective memory loss following nucleus basalis lesions: long term behavioral recovery despite persistent cholinergic deficiencies. AB - Rats were trained for several months to perform a radial arm maze task and then given either sham or ibotenic acid lesions of the nucleus basalis magnocellularis (NBM), the primary cholinergic projection to the neocortex. The lesion produced a profound and apparently selective disturbance in memory for recent events. Further testing revealed that although the memory deficit persisted for several weeks, a gradual but complete recovery eventually occurred. Moreover, when these functionally recovered rats were later tested on a passive avoidance task that is normally sensitive to lesions of the NBM, no deficit was found. Thus, the post lesion recovery of function generalized to a different memory test, upon which no post-lesion practice had been given. Post-mortem determinations revealed that the lesions caused marked neurodegeneration of the NBM, and decreases in both cortical choline acetyltransferase activity and high affinity choline uptake, but had no effect on density of muscarinic receptors. No evidence of neuronal recovery or neurochemical compensatory changes in the cholinergic system was found in the cortical projection areas, lesion site, or in parallel cholinergic systems terminating in the hippocampus or olfactory bulb. These results support the idea that the cortically-projecting cholinergic cells of the NBM normally play an important role in mediating recent memory. However, they also demonstrate that any simple relationship between the function of this brain region and the mediation of recent memory is unlikely. Finally, the results of this study direct attention toward issues related to the mechanisms involved with the recovery of function, and the extent to which degeneration of this brain area may contribute directly to the severe disturbance of cognitive function associated with certain neurodegenerative diseases (e.g., Alzheimer's, Pick's and Parkinson's disease). PMID- 4041043 TI - Age of testing as a factor in the behavioral effects of early lead exposure in rats. AB - The behavioral effects of postnatal administration of lead during weaning were tested in young and adult rats. Rats received either 10 mg/kg IP lead acetate or equimolar sodium acetate daily for the first twenty days of life. Tests of performance on an 8-arm radial maze and a passive avoidance task were begun at 25 days after birth or 90 days after birth. Lead-treated rats did not perform significantly different than control rats on the radial arm maze at either age tested. Young lead-treated rats performed with significantly longer lick latencies than young control rats on the passive avoidance task. Adult lead treated rats performed with shorter food latencies than adult control rats. A group of young rats was retested on the passive avoidance task at 150 days after birth. Performance on the retest was similar to their early performance. Differences in performance of young and adult lead-treated animals on the passive avoidance task are discussed in terms of an interaction of the effects of lead exposure, maturation, and early experience. PMID- 4041044 TI - The role of central noradrenergic neurons in electroconvulsive shock-induced muricide inhibition in olfactory bulbectomized rats. AB - In order to elucidate the role of central monoaminergic neurons in electroconvulsive shock (ECS)-induced muricide inhibition in the olfactory bulbectomized rat (OB rat), we examined the effect of chemical or electrical lesions of each monoamine-containing neuron on ECS-induced muricide inhibition. ECS-induced muricide inhibition was antagonized by 6-hydroxydopamine (6-OHDA) treatment and locus coeruleus lesions, while it was unaffected by desipramine + 6 OHDA, substantia nigra lesion, and desipramine + 5,7-dihydroxytryptamine. The present results strongly suggest that ECS-induced muricide inhibition of the OB rat is due to increased activity of the noradrenaline but not of dopamine and serotonin neurons. PMID- 4041045 TI - Effects of tunnel maze complexity on caffeinic hyperactivity in the rat. AB - The study investigated effects of caffeine on spontaneous tunnel locomotion without consummatory reward. The stimulant effects consisted in delayed intrasession habituation, and they differed in magnitude according to dosage and the complexity of the tunnel arrangements. In a simple hexagonal tunnel without choice points, 16 mg/kg BW produced greater stimulation than other doses, and this most efficient dose became less effective if tunnels were arranged according to the radial maze paradigm. No stimulation was obtained if an open field was incorporated into the maze. Caffeine also had no effect on open field behavior, but it tended to improve the efficiency of radial arm maze patrolling, and its significantly depressed exploration of short tunnel arms branching from the radial arms in favor of exploration of the more distant radial tunnel ends. PMID- 4041046 TI - Acute and chronic behavioral interactions between phencyclidine (PCP) and amphetamine: evidence for a dopaminergic role in some PCP-induced behaviors. AB - Amphetamine and phencyclidine (PCP) are both proposed to exert effects on unconditioned behavior through dopaminergic mechanisms. However, a relatively complete characterization of their effects in rats reveals markedly different response profiles. Furthermore, whereas acute co-administration of amphetamine and PCP resulted in an increase in one component of stereotypy, repetitive head movements, two measures of locomotor activation, i.e., ambulation and nonfocused sniffing, were unchanged, and rearings were reduced. In addition, the response alterations which occur with repeated administration of these drugs did not display cross-sensitization. Thus, although repeated daily injections of amphetamine, which produced progressive locomotor augmentation, sensitized animals to the locomotor-stimulating effects of PCP, repeated PCP treatment, which also resulted in locomotor augmentation, decreased the locomotor response to a challenge injection of amphetamine. These findings suggest significant differences in the mechanisms underlying the effects of acute and repeated administration of PCP and amphetamine. PMID- 4041047 TI - A twin study of cardiac reactivity and its relationship to parental blood pressure. AB - The cardiac reactivity of 40 monozygotic and 40 dizygotic pairs of young male twins was monitored during psychological challenge, as afforded by a video game. The observed pattern of variation could not be accounted for solely by environmental factors. In fact, a simple genetic model that implicated additive genetic effects, along with those stemming from individual environments, best fitted the data. In addition, cardiac reactions were substantially greater for subjects whose parents both had relatively elevated blood pressure. Overall, these data suggest individual differences in cardiac reactivity have a heritable component, and that high reactivity may be a precursor of elevated blood pressure. PMID- 4041048 TI - Effects of malnutrition and environment on the acquisition and extinction of avoidance behavior in rats. AB - Twelve newborn rats were fed by mothers maintained on a protein-deficient diet (12% casein, M) during lactation, and 12 rats fed by mothers maintained on a diet containing 25% casein were used as controls (C). After weaning, all animals were fed standard lab ration. Half of each group was housed individually (MI and CI), while the other half was allowed to live in pairs (MP and CP). When adult, all animals were trained to avoid footshocks by jumping onto a platform. Training sessions consisted of 40 trials starting with a 20 sec light stimulus (CS) and followed by a 2 sec, 0.6 mA shock (US) with an average intertrial interval of 54 sec. When all animals displayed consistent avoidance behavior, the extinction phase was initiated. The procedure was the same as for the training sessions except that the shock generator was disconnected. Extinction continued until each animal showed a 50% reduction in avoidance performance. During acquisition, MI learned faster than CI and CI showed greater avoidance performance than CP, but no differences were observed between MP and CP. During extinction, group M responded more persistently than group C. The present acquisition results may explain the contradictory data reported in the literature with respect to the effects of malnutrition on avoidance performance, since environmental stimulation was shown to reduce the effects of early malnutrition. Individually housed animals showed greater avoidance performance during both phases. PMID- 4041049 TI - Pentobarbital-induced drinking does not rely on a renal dipsogen. AB - Injections of pentobarbital have been shown to produce drinking in both deprived and nondeprived rats and a number of other studies have shown that pentobarbital is a potent renin releasor. Since renin has been shown to be involved in thirst regulatory mechanisms and since the dipsogenic actions of other renin-releasing agents have been blocked by nephrectomy, we sought to determine whether or not pentobarbital-induced drinking relies on a renal dipsogen. Rats were either "sham" operated or nephrectomized under ether anesthesia. Five to six hours later, animals in each group were injected with either 9.5 mg/kg pentobarbital sodium or vehicle, and intakes were measured 60 minutes later. Statistical analysis of water intakes indicated that pentobarbital produced significant drinking in both control operated and in nephrectomized rats, and that the intakes in these two groups did not differ. These results indicate that pentobarbital-induced drinking is not secondary to increased plasma renin activity and may suggest the involvement of central mechanisms in the drinking response. PMID- 4041050 TI - Acute and conditioned blood pressure changes in relation to social and psychosocial stimuli in rats. AB - The naturally occurring tendency to compete with other rats for territorial space has been used to study individual behavior characteristics and blood pressure reactivity to social stimuli in adult male TMD-S3 rats. The competitive characteristics of the individual rats are consistent in two different social situations (victory and defeat). Blood pressure responses during the victory of home territory rats over intruders was more pronounced in the more competitive animals. In addition to defeat by a trained fighter rat, the experimentals were also psychosocially stimulated by the fighter while it was confined in a small wire mesh cage. The blood pressure response to this event was enhanced by the prior defeat of the test animal by the one now confined to the small cage. This response was more pronounced in competitive rats. This approach has potential as an animal model of etiological processes in socially induced hypertension. PMID- 4041051 TI - Timing of parturition and postpartum mating in Norway rats: interaction of an interval timer and a circadian gate. AB - Two temporal variables have been implicated in the timing of postpartum heat in Norway rats: time of day and time since parturition. The nature of the interaction between these variables is not clearly understood. We extend previous observations on this problem to freely behaving animals continuously videotaped during parturition and postpartum mating in a seminatural habitat. The timing of postpartum mating is best described by a model in which an interval timer is coupled to a circadian gating mechanism. Interactions between circadian and interval timing mechanisms may be widespread in the neuroendocrine control of behavior. PMID- 4041052 TI - Time-contingent change in infanticide and parental behavior induced by ejaculation in male mice. AB - About 50% of sexually-naive male CF-1 mice (Mus musculus) commit infanticide (kill young). But, 80-90% of male mice commit infanticide between 1-4 days after mating. Between 12 and 50 days after mating infanticide is inhibited and most males (80-100%) behave parentally toward young (they build a nest, retrieve and groom the young, and hover over the young to keep them warm). Beginning at 60 days after mating, infanticide is again facilitated and parental behavior is inhibited (70-80% of males commit infanticide). The facilitation and inhibition of infanticide as a function of time after mating is mediated by the act of ejaculating rather than by mounting and intromitting during mating or by cohabiting with a female either before or after mating. The experience of committing infanticide either prior to mating or within the first 4 days after mating does not influence the facilitation of parental behavior that occurs 12 days after mating. But, repeated contact with young after males become parental serves to maintain parental behavior for an extended period of time. The age of the young (newborn-20 days old) utilized as stimulus animals does not influence these time-dependent changes in the behavior of male mice after ejaculation. This phenomenon is unique in that a response (infanticide) to a novel stimulus (young) is facilitated, then inhibited, and then facilitated again as a function of time between an event (ejaculation) and exposure to the novel stimulus.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4041053 TI - Behavioral insensitivity to progesterone during lactation in female rats. AB - Lactating female rats failed to display sexual receptivity after receiving 50 micrograms of estradiol benzoate followed by 1 mg of progesterone. Lactating rats appear to be insensitive to progesterone, based on several experiments. In ovariectomized control rats receiving moderate estrogen priming (1 microgram EB for 3 days), progesterone greatly facilitated sexual receptivity; similarly estrogen-primed lactating females showed no responsiveness to progesterone injections, even at a high dose of progesterone (10 mg). Consistent with this reduced behavioral responsiveness to progesterone, lactating females had significantly reduced nuclear progestin receptor levels after an injection of 1 mg progesterone compared to ovariectomized controls. On the other hand, both ovariectomized controls and lactating rats responded with high levels of receptivity to 3 days of priming with 10 micrograms of estradiol benzoate (without progesterone). Lactating females treated for 3 days with a moderate dose (1 microgram) of estradiol benzoate showed slightly reduced receptivity compared to ovariectomized controls; this result could reflect a reduced sensitivity to estrogen but is more likely related to the somewhat lower serum levels of estradiol and consequently lower nuclear estrogen leading to a reduced sensitivity to progesterone cannot be eliminated (since animals respond to progesterone only after estrogen priming); however, the reported results favor the idea that lactating females are primarily refractory to progesterone and do not have a generalized insensitivity to estrogen. PMID- 4041054 TI - Transition from pup killing to parental behavior in male and virgin female albino rats. AB - In the first part of this study, the effect of habituation to pups was examined in virgin female and male Sprague-Dawley rats that committed infanticide in a screening test. With repeated exposure to test pups (5-10 days old), the rats ceased to commit infanticide and came to behave parentally. Preexposure to inaccessible pups (confined inside wire-mesh baskets) did not accelerate the rate of disappearance of infanticide during subsequent contact with young, which suggests that pup killing is not a neophobic response to the novelty of young. In the second part of the study, three groups of infanticidal male Wistar rats were mated and tested for their responses towards unrelated pups after different intervals of cohabitation with their mates. The males continued to commit infanticide at the time that their mates were at midpregnancy or 24 hr before parturition, but males that cohabited with their mates till day 9 postpartum no longer attacked the young. Thus, the mother rat, presumably by means of postpartum aggression, renders her mate noninfanticidal, thereby reducing the likelihood of her offspring being harmed when she is away from the nest. PMID- 4041055 TI - Sexual behavior frequency and biphasic ovulatory type menstrual cycles. AB - College students whose menarche had occurred 7 years previously, prospectively recorded menstrual and sexual behavior history for 14 weeks as well as basal body temperatures. Regular weekly coital activity associates with the highest incidence of fertile type cycles in this sample of young women as follows: (1) Regular weekly heterosexual behavior was associated with 29.5 +/- 3 day menstrual cycle length. Less frequent sexual activity (sporadic) and celibacy were associated with an increased frequency of aberrantly short and long cycle lengths. (2) Either of two heterosexual behaviors (coitus and/or genital stimulation by a man) were behaviors which were adequate as associates of 29.5 +/ 3 day cycles. (3) Self-stimulation (masturbation to orgasm) was inadequate as an associate of the above-described pattern of menstrual cyclicity. (4) Women with regular weekly coital activity had the highest incidence (90%) of fertile type basal body temperature (BBT) rhythms. Sporadically active women had the next highest incidence (55%) of fertile type BBT rhythms. Celibate women had the lowest incidence (44%) of fertile type BBT's. PMID- 4041056 TI - Fractionation of the cataleptic bracing response in rats. AB - In haloperidol-treated rats, bracing, i.e., resistance to displacement along a horizontal surface, was found to involve four components: gripping by the digits, extension by the limbs, stiffening of the body axis and arching the vertebral column towards the displacing force. Labyrinthectomy weakened the bracing of the forequarters as did application of a head bandage. Labyrinthectomy, when combined with head bandage, completely abolished all forequarter bracing responses. Neither manipulation affected the bracing responses of the hindquarters. The hindquarter bracing reaction was abolished by application of an abdominal bandage, which left most of the forequarter responses intact. Isolation of fore- and hindquarter bracing responses revealed that whereas gripping by the digits and extension by the limbs could occur independently in either part of the body, stiffening of the body axis and arching of the vertebral column originated in the hindquarters. However, although these latter components of bracing originate in the hindquarters, as evidenced by their abolition with application of an abdominal bandage, their recruitment into the anterior of the body only occurred when the bracing of the forequarters was unimpaired. Either labyrinthectomy or head bandage prevented stiffening and arching of the vertebral column from occurring in the forequarters, even though these procedures had no effect on the hindquarters. Labyrinthectomy, head bandage and abdominal bandage all fractionated the bracing response over a wide range of haloperidol dosages (0.5, 1.0, 2,5, 5,0 and 7.5 mg/kg). PMID- 4041057 TI - Wheel-running during anoestrus and oestrus in the ferret. AB - Wheel-running activity was studied in female ferrets (Mustela putorius furo), during periods of anoestrus and oestrus, as well as after gonadectomy. During anoestrus wheel-running was restricted to the hours of illumination, but during oestrus extended into the dark period and was increased overall, with the number of wheel revolutions being doubled or trebled. In spayed females wheel-running was mostly limited to the light periods. PMID- 4041058 TI - Thermal control of maternal contact bouts: the interbout interval. AB - Cooling mother rats by means of sodium salicylate injections did not curtail the intervals between maternal contact bouts. To the contrary, the interbout intervals were prolonged, suggesting that the relief from hyperthermia is a necessary but not a sufficient condition for the reinitiation of pup contact by mother rats. The ability of sodium salicylate to suppress maternal temperature suggests that pyrogenic and lactational increases in temperature may have some common feature. PMID- 4041059 TI - Neurochemical basis of stress-induced depression. PMID- 4041060 TI - Involvement of opioid peptides in the analgesic, immunosuppressive, and tumor enhancing effects of stress. PMID- 4041062 TI - Cell cycle age dependence for radiation-induced G2 arrest: evidence for time dependent repair. AB - Exponentially growing eucaryotic cells, irradiated in interphase, are delayed in progression to mitosis chiefly by arrest in G2. The sensitivity of Chinese hamster ovary cells to G2-arrest induction by X rays increases through the cell cycle, up to the X-ray transition point (TP) in G2. This age response can be explained by cell cycle age-dependent changes in susceptibility of the target(s) for G2 arrest and/or by changes in capability for postirradiation recovery from G2-arrest damage. Discrimination between sensitivity changes and repair phenomena is possible only if the level of G2-arrest-causing damage sustained by a cell at the time of irradiation and the level ultimately expressed as arrest can be determined. The ability of caffeine to ameliorate radiation-induced G2 arrest, while inhibiting repair of G2-arrest-causing damage makes such an analysis possible. CHO cell monolayers were irradiated (1.5 Gy), then exposed to 5 mM caffeine for periods of 0-10 hr. Cell progression was monitored by the mitotic cell selection procedure. In the presence of caffeine, progression of irradiated cells was relatively unperturbed, but on caffeine removal, G2 arrest was expressed. The duration of G2 arrest was independent of the length of the prior caffeine exposure and, since cells of all ages were ultimately examined, the duration of arrest was also independent of cell cycle age at the time of irradiation. This finding indicates that the target for G2-arrest induction is present throughout the cell cycle and that the level of G2-arrest damage incurred is initially constant for all cell cycle phases. The data are consistent with the existence of a time-dependent recovery mechanism to explain the age dependence for radiation induction of G2 arrest. PMID- 4041061 TI - Nocturnal serum melatonin in major depressive disorder before and after desmethylimipramine treatment. PMID- 4041063 TI - DNA polymerase alpha and beta activities during the cell cycle and their role in heat radiosensitization in Chinese hamster ovary cells. AB - The levels of DNA polymerase alpha and beta activities were measured during the cell cycle using a total cell homogenate technique. The results indicate a decrease in the levels of both enzyme activities during the G1 phase and a gradual increase as cells enter the S phase. The recovery of DNA polymerase activities was measured after heating for 10 min at 45.5 degrees C during the G1 phase (1.5 hr after mitotic release) or S phase (8-9 hr after mitotic release). This treatment reduced the levels of DNA polymerase beta activity to 20-30% and DNA polymerase alpha activity to 40-50% of their control activity for both G1 and S phase. The activity of DNA polymerase beta recovered fully during 20-25 hr after heating for both G1 phase or S phase cells. There was no recovery of the activity of DNA polymerase alpha during this time. Survival was measured when cells were irradiated (4 Gy) at various times after hyperthermia (10 min at 45.5 degrees C), and for both G1 and S phase the interaction between heat and X rays disappeared by 20-25 hr after heating and the same increase was observed for the recovery of DNA polymerase beta activity. Furthermore, treatment with cycloheximide inhibited protein synthesis and prevented recovery from heat damage assayed in terms of both cell survival and beta polymerase activity. These results, in addition to experiments with heat protection by glycerol or thermotolerance induced with sodium arsenite or fractionated heat doses, suggest that beta polymerase may be an important enzyme involved in repairing X-ray induced damage that can result in cell lethality. PMID- 4041064 TI - Plasminogen activator activity in lung and alveolar macrophages of rats exposed to graded single doses of gamma rays to the right hemithorax. AB - Male rats were sacrificed 2 or 6 months after a single dose of 0-30 Gy of 60Co gamma rays to the right hemithorax. At autopsy, macrophages were lavaged from the right lung, counted, and frozen. The right (irradiated) and the left (shielded) lungs were frozen, then assayed for plasminogen activator (PLA) activity by the fibrin plate lysis method. Freeze-thawed macrophages were assayed for both PLA activity (125I-fibrin clot lysis method) and fibrinolytic inhibitor activity (inhibition of urokinase-induced fibrin lysis). There was a linear, dose dependent decrease in right lung PLA activity over the dose range of 10-30 Gy at 2 and 6 months postirradiation, reductions of 3.1 and 2.6% per Gy, respectively. PLA activity at all radiation doses was 10-15% higher at 6 months than at 2 months (P less than 0.05), indicative of a partial recovery of this endothelial function in the irradiated lung. There were no significant changes in PLA activity in the shielded left lung at any dose or time. There also was a linear, dose-dependent increase in the number of macrophages lavaged from the right lung at both 2 and 6 months postirradiation, with larger numbers recovered after all doses at 2 months. PLA activity per 10(6) macrophages decreased with increasing radiation dose at both autopsy times, closely paralleling lung PLA activity. This radiation-induced decrease in macrophage PLA activity was not due to increased fibrinolytic inhibitor activity in the irradiated macrophages. These data quantitate the dose response and time course of radiation-induced fibrinolytic defects in rat lung and suggest that information obtained from a minimally invasive procedure such as bronchoalveolar lavage may serve as an index of the degree of pulmonary fibrinolytic dysfunction after irradiation. PMID- 4041065 TI - Narcotic antagonist potentiation of apomorphine drug effect: a stereospecific, centrally mediated drug action. AB - Systemic pretreatment with naloxone but not its (+)-enantiomer significantly potentiated apomorphine-induced stereotypic climbing activity in mice. Systemic or central pretreatment with naltrexone also significantly potentiated the apomorphine drug effect. The N-methyl derivative of naltrexone had no influence when administered systemically but significantly potentiated the apomorphine drug effect when administered centrally. These findings suggest that narcotic antagonist potentiation of apomorphine-induced stereotypic climbing in mice is a stereospecific phenomenon that originates in the central nervous system. PMID- 4041066 TI - Effect of truncal vagotomy on intestinal phase of pancreatic polypeptide release in dogs. AB - In order to elucidate the role of the vagus nerve in the intestinal phase of pancreatic polypeptide (PP) release, mongrel dogs were given a 4-min intraduodenal infusion of saline, 20% glucose, or 10% soybean oil solution (50 ml each), before and one month after truncal vagotomy including pyloroplasty (TV). The saline infusion did not change the basal PP level, while the glucose infusion elicited a monophasic transient PP release, and the soybean oil infusion elicited a monophasic prolonged PP release in the intact dogs. The PP response following glucose infusion was almost abolished after TV, while the PP response to fat was attenuated, but a significant increase was nevertheless observed after TV. These results suggest that the vagus nerve has an important role in the intestinal phase of PP release and that other factors, e.g. hormonal, might also be involved in the regulatory mechanism, especially after fat loading. PMID- 4041067 TI - Effects of pimozide and domperidone administration on prolactin levels in neonatally estrogenized female rats. AB - The effects of two dopaminergic blockers, pimozide and domperidone, on the prolactin secretion were investigated in adult female rats treated neonatally with estrogens (100 micrograms of estradiol benzoate s.c. on day 1). These rats showed hyperprolactinemia (556 micrograms/l vs 57.7 in oil-injected) and treatment with pimozide or domperidone failed to increase prolactin levels in the adult age. These results suggest that the hyperprolactinemia in neonatally estrogenized female rats is produced by loss of the dopaminergic inhibition on prolactin secretion, so that the pharmacological blockade of dopaminergic receptors is uneffective. The dopamine levels in hypothalamus were similar in control and estrogenized females suggesting that failure in dopaminergic inhibition is due to a decrease in dopamine secretion to portal vessels. PMID- 4041068 TI - Influence of perioperative cis-platinum on breaking strength of bowel anastomoses in rats. PMID- 4041069 TI - [A case of aortitis syndrome with asymmetric septal hypertrophy, systolic anterior motion of anterior mitral leaflet and pressure gradient within the left ventricle]. PMID- 4041071 TI - [A case of hypertrophic obstructive cardiomyopathy observed during mild hypertension]. PMID- 4041070 TI - [A case of pheochromocytoma with left ventricular configuration mimicking hypertrophic obstructive cardiomyopathy]. PMID- 4041072 TI - [Chromosome aberrations in 334 individuals with various types of abortion (including 144 couples)]. PMID- 4041073 TI - [The 24-hour excursion and diurnal rhythm of blood sugar in normal pregnant women close to term]. PMID- 4041074 TI - Circadian rhythm in plasma immunoreactive somatomedin-C in children. AB - Fifteen boys and 27 girls, 11 +/- 2 years of age were studied over a single 24 hour span during the month of June. Statistically significant circadian rhythms of plasma immunoreactive somatomedin-C (SM-C) concentration, immunoreactive growth hormone (hGH) and cortisol concentration were found, which show marked differences in timing. The highest values of somatomedin-C occurred in the early evening hours (acrophase 19:08) in contrast to growth hormone which showed its peak values during the night and cortisol, which peaked in the morning hours. These observations are of interest for the physiologic regulation of somatomedin C as well as for the clinical evaluation of plasma immunoreactive somatomedin-C concentrations, and for studies of the response of somatomedin-C to hormonal and/or pharmacologic manipulation. PMID- 4041075 TI - Radioimmunoassay of human sex hormone binding globulin: improved radioiodination procedure. AB - Sex hormone binding globulin (SHBG), purified by affinity chromatography from retroplacental blood plasma, was reacted with 3-(p-hydroxyphenyl) propionic acid N-hydroxysuccinimidyl ester (PHPPS, Bolton-Hunter reagent). The derivative of SHBG obtained (parahydroxyphenylpropionyl-SHBG; PHPP-SHBG) was stable and could, in contrast to underived SHBG, be efficiently 125I-iodinated with a lactoperoxidase technique. The PHPP-SHBG labelled with 125I had good antiserum binding and stability properties and was used for radioimmunoassay (RIA) of SHBG in serum. The RIA requires a total incubation time of 3 h. It has been standardized with purified SHBG and has a sensitivity of 5 micrograms/l, giving a lowest detectable concentration in the routine procedure (samples diluted 1:40) of about 0.2 mg/l. Variation within and between assay was 4.1% and 7.2%, respectively, for samples with values within the normal range. Values obtained by this RIA procedure correlate well with those obtained by a dihydrotestosterone binding method and by an electroimmunoassay technique. The mean serum concentration of SHBG in healthy, regularly menstruating women (n = 42) was 3.7 +/- 1.0 (SD, standard deviation) mg/l and in healthy men (n = 100) 2.0 +/- 0.9 mg/l. PMID- 4041076 TI - Multiple co-existing sexually transmitted diseases in a bisexual man. AB - The authors report an interesting and instructive case of a bisexual man with four concurrent sexually transmissible infections: secondary syphilis, genital herpes, gonococcal proctitis, and asymptomatic chlamydial urethritis. The case illustrates the necessity for a systematic approach to the diagnosis and management of multiple co-existing sexually transmitted diseases, and it underscores the importance and difficulty of contact-tracing in this patient population. PMID- 4041077 TI - Group support for parents of high risk neonates: an interdisciplinary approach. AB - Many parents are unable to develop a satisfying relationship with their sick newborn. Although data are divided over the critical nature of the attachment process, measures to assist parents and reduce socio-environmental stresses are considered desirable. Group support is one such measure which can provide parents with a commonly needed component of neonatal intensive care. In the group described, weekly sessions are informal, encouraging discussion, an understanding of neonatal care and recognition that some emotional and coping disturbance is normal. Staff involved are an interdisciplinary team (social worker, doctor and nurse). The group requires no special funding and time commitment is low considering the support provided. We have met weekly for five years with sustained attendance. No control group exists but parents appear increasingly comfortable in the nursery and able to achieve more meaningful and ongoing interaction with their infant and the staff. PMID- 4041078 TI - Ectopia cordis thoracalis with craniofacial defects resulting from early amnion rupture. AB - A 33-week-gestation fetus was evaluated as having ectopia cordis thoracalis, midline sternal cleft, frontonasal dysgenesis, a midfacial cleft, and amniotic bands. Fibrous bands were attached to the apex of the heart, face, and the brain. There were no associated limb defects or scoliosis. The findings in this fetus and those in the literature suggest that acute amnion rupture in the third week of gestation may be the cause of these defects. Mechanical teratogenesis by tissue bands adherent to the heart may lead to ectopia cordis. The changes seen in the thorax, face, and brain suggest pressure necrosis, incomplete morphogenesis, tearing and tethering by amnion, and compression as a cause for these defects. A spectrum of defects is found following amnion rupture with the abnormalities being dependent upon the timing of the event. Ectopia cordis with amniotic bands appears to have an etiology distinct from isolated ectopia cordis. This suggests several different etiologies for ectopia cordis. PMID- 4041079 TI - [Typhlohepatitis in ostriches (Struthio camelus) caused by a Histomonas infection]. AB - Acute typhlohepatitis was diagnosed in two juvenile ostriches (Struthio camelus). Gross pathology and histologic examination revealed a striking resemblance with histomoniasis in Galliformes. PMID- 4041080 TI - An analysis of the child survival hypothesis in Jordan. AB - Data from the 1976 Jordan Fertility Survey are used to examine the association between infant mortality and fertility behavior. After controlling for socioeconomic and demographic variables, a strong positive association was found between infant mortality and fertility behavior; women who experience infant deaths tend to make up for the loss of children. However, in terms of surviving children (surviving to age one year), the replacement effect is far from complete. This study also shows that reporting or recording deaths as having occurred after infancy, when in fact they have occurred before age 12 months, tends to result in an underestimate of the mortality-fertility association. However, the bias is statistically significant (at the 0.05 level) only when 50 percent or more of infant deaths are so misreported. PMID- 4041081 TI - Zoonotic cutaneous leishmaniasis in Saudi Arabia: lesions healing naturally in man followed by a second infection with the same zymodeme of Leishmania major. AB - A patient with a previous history of an infection with Leishmania b. braziliensis contracted zoonotic cutaneous leishmaniasis (ZCL) in the Al-Hassa oasis, Eastern Province, Saudi Arabia. Five lesions healed spontaneously over a period of 40 weeks without treatment. A year after acquiring ZCL he became infected again in the same focus. Isolates of parasites at both episodes were identified as L. major, zymodeme LON-4. Compared with the first infection of ZCL, parasites were fewer in the lesions on the second occasion, the lesions were smaller and healing was quicker (10 weeks). This work and a previous report of patients with active lesions and leishmanial scars suggest that second infections of L. major are not uncommon in the oasis where no autochthonous infections of other species of Leishmania have yet been recorded in man and only one species of Phlebotomus (P. papatasi) is known. PMID- 4041082 TI - Ocular leprosy. PMID- 4041083 TI - Idiopathic granulomatous orchitis. AB - A case of granulomatous orchitis in a 52-year old negro male is reported. The distinction between granulomatous orchitis and cancer is important in particular in coloured people where the former is not rare while testicular cancer is uncommon. PMID- 4041084 TI - [Mitral valve prolapse in 2 twin homozygote sisters]. PMID- 4041085 TI - [Potential danger to pacemaker patients during transurethral operations. Clinical and experimental studies]. AB - The high sensitivity of modern demand pacemakers to HF-currents, as used for the TUR, could be shown by an in vitro model, animal experiments and clinical investigations. It was possible to characterise the type specific HF-sensitivity by means of individual functions. Furthermore, it could be proven that almost every external HF-signal could be blocked by switching the demand pacemaker to its fixed magnet frequency, a most important procedure in order to maintain patient safety during a transurethral resection. PMID- 4041086 TI - [Operative complications in transurethral operations: causes and prevention]. AB - Complications resulting from transurethral operations can be classified as intraoperative, directly postoperative and late complications. Specific problems are related to prostatic resection, resection of bladder tumors or lithotripsy of bladder stones. An analysis of these problems is presented based on in the experience in more than 10 000 transurethral operations. Directives are developed to avoid additional intraoperative harm and minimize resulting problems. Methods for correction of iatrogenic complications are explained. PMID- 4041087 TI - [Tuberculosis of the breast simulating cancer]. PMID- 4041088 TI - [Decisions of the February Plenum of the Central Committee of the Communist Party and the tasks facing the biological sciences]. PMID- 4041089 TI - Sequence of the DNA-binding protein of a human subgroup E adenovirus (type 4): comparisons with subgroup A (type 12), subgroup B (type 7), and subgroup C (type 5). AB - The nucleotide sequence of the gene for the single-stranded DNA-binding protein of adenovirus type 4 (Ad4) has been determined. The gene codes for a protein of 512 amino acids. Comparison of the amino acid sequence with those previously determined for Ad5, Ad12, and Ad7 allowed identification of regions that are conserved between the four serotypes. These include stretches of 9, 9, and 12 amino acids in the carboxy-terminal domain of the protein; these sequences are similar to those identified in the single-stranded DNA-binding proteins of procaryotes as being important for interaction of the protein with single stranded DNA. A conserved region of four amino acids in the amino-terminal domain is identical in sequence to a region of the SV40 large T antigen that has recently been implicated in the nuclear localization of the protein. Other conserved amino acids that may be important for the three-dimensional structure of the protein have also been identified. The overall homology between the DBPs of the four serotypes is 17.2% in the amino-terminal domain, 47.8% in the carboxy terminal domain. Two-way comparisons between the DBPs of the four serotypes indicates that the DBP of Ad4 is most closely related to that of Ad7. PMID- 4041090 TI - [Is it possible to diagnose and better characterize hypertrophic cardiomyopathies using ECG?]. PMID- 4041091 TI - [Testosterone, albumin and sex steroid-binding globulin in the blood serum of patients with laryngeal cancer]. AB - Since endocrine factors play a role in the etiology and pathogenesis of precancerous and tumor diseases of the pharynx, the study was concerned with assays of total testosterone, albumin, sex steroid-binding globulin and free and protein-bound androgens in the blood serum of patients with malignant and benign tumors of the larynx. Laryngeal cancer patients revealed raised levels of total, free and albumin-bound testosterone matched by a lower concentration of sex steroid-binding globulin. Maximum differences between the study groups were established in the relationship between the fraction of testosterone associated with sex steroid-binding globulin and that of free androgen. An important role of androgens in the pathogenesis of laryngeal cancer was inferred. Further studies of androgen secretion and transport by blood proteins in laryngeal cancer patients are essential for the investigations of pathways of sex steroid hormones action. PMID- 4041092 TI - [Effect of soybean kefir on the course of hypercholesterolemia in patients]. PMID- 4041093 TI - Iridocyclitis is not characteristic of Still's disease. PMID- 4041094 TI - Conjugation of disodium 6-chloro-4-oxo-10-propyl-4H-pyrano[3,2-g]quinoline-2,8 dicarboxy late with glutathione in the rat. AB - Disodium 6-chloro-4-oxo-10-propyl-4H-pyrano[3,2-g]quinoline- 2,8-dicarboxylate (I) is conjugated with glutathione (GSH) both in vitro and in vivo by nucleophilic replacement of the chlorine substituent in (I). The reaction is catalysed by rat-liver supernatant. The GSH conjugate is the principal excretory product in the rat bile after i.v. administration of (I), accounting for approximately 60% of the dose and 95% of the biliary excretion. Its structure was determined by synthesis and spectroscopic analysis. PMID- 4041095 TI - [Intellectual and psychological damage caused by breech delivery]. PMID- 4041096 TI - [Effect of genotype and environment on individual features of the orientation reaction in man]. AB - Autonomic responses and evoked potentials were recorded in situation of orienting reaction in 86 twins. On the basis of experimental and literature data a hypothesis is suggested on the existence of two subsystems of orienting reaction- a block of informational regulation and a block of motivational regulation characterized by different functions and, probably, by different neurophysiological mechanisms. The activity of the first block is formed mainly by environmental factors while the activity of the second one--mainly by the genotype. PMID- 4041097 TI - [Correlation between genetic and environmental factors in the display of predatory reactions in the rat]. AB - Manifestation of the hunting and mice-killing reactions by non-linear rats observers did not depend on the presence of rats killing mice. The absence of such dependence was observed in conditions of free access to food, of food deprivation stimulating predatory aggressiveness, and also of learning in the early postnatal period. Acquisition of the habit of eating killed mice by the rats-observers was facilitated in the presence of rats executing this reaction. It is suggested that in manifestation of the aggressive component of predatory behaviour of rats, a greater role is played by inborn mechanisms while environmental factors are more significant for organization of the alimentary mechanism. PMID- 4041098 TI - [Level of dopamine in structures of the nigro-striatal and mesolimbic systems of the brain in experimental pathology of higher nervous activity in the rat]. AB - Rats, unable to elaborate a discriminative avoidance reflex to two acoustic stimuli in conditions of time deficit, and displaying non-adaptive forms of behaviour in the process of conditioning (non-escape of the electric shocks, absence of responses to both differentiated stimuli), possess a lower dopamine level in the striatum and a higher one in the olfactory tubercle in comparison to the animals without non-adaptive reactions. PMID- 4041099 TI - [Spike activity of neurons of the ventromedial hypothalamus of the rat during stress]. AB - In fixed Wistar line rats, neuronal activity of the ventromedial hypothalamus was studied in conditions of acute emotional stress elicited by electric stimulation of the ventromedial hypothalamus stochastically alternating with electrocutaneous stimuli. Distinctions were revealed in neuronal activity of the animals with different stress resistance. The pattern of neuronal impulse activity proved to be the most informative one. PMID- 4041100 TI - [Isolation and properties of a nonspecific adhesive factor from the blood serum of warm-blooded animals and man]. PMID- 4041101 TI - [Primary, non-pregnancy-induced choriocarcinoma]. AB - The case of a primary chorioncarcinoma of the ovary is presented in an eighteen year old nulligravida. Following a primary operation, including the exstirpation of the inner genital organs, an antineoplastic combination chemotherapy was done. The partial remission obtained was of a duration of 5 months only, and the patient died after having survived 8 months because of metastatic generalization. PMID- 4041103 TI - [Immune response and the formation of immunologic memory to Staphylococcus in mice of different genotypes]. AB - The time course of changes in the number of antibody-forming cells in the spleen in the primary and secondary immune response to staphylococcal corpuscular antigen was studied in experiments on mice. C3H mice were found to be highly responsive, while A/Sn mice showed low response, the opposite character of immune responsiveness to this antigen in the animals of the above-mentioned genotypes increasing after the second immunization. C57BL/6, CBA, DBA/2, BALB/c and (CBA X C57BL/6) F1 mice showed comparatively moderate antibody formation in response to staphylococci. The formation of immunological memory to this antigen depended on the genotype of mice and was determined by the intensity of antigenic action: high priming doses of staphylococci proved to be most effective; low doses of the antigen were not effective or produced only short-term immunological memory to staphylococci in mice. PMID- 4041102 TI - [The local specific immune response to Staphylococcus aureus protein A in human tonsillar lymphoid tissue]. AB - Formation of antibodies and development of delayed hypersensitivity to protein A are usual components of the immune response of tonsillar lymphoid tissue to S. aureus infection in chronic tonsillitis in man. The preparations of transfer factor, produced from human tonsillar T-cells, show increased activity in the intraspecific transfer of delayed hypersensitivity to staphylococcal protein A from humans to mice. PMID- 4041104 TI - [Penetration and accumulation of 14C-ethanol in the brain and liver of female rats exposed to long-term alcohol and in the tissue of the fetus]. AB - In their experiments on female rats which had been given 10% ethanol for 10 months the authors showed the characteristics of 14C-ethanol accumulation in the structures of the brain and liver of the animals and changes in these parameters during pregnancy. The penetration and accumulation of 14C-ethanol in the brain and liver of fetuses of chronically alcoholized animals were found to be different. PMID- 4041105 TI - [Ultrastructural analysis of the phenomenon of acute neuronal swelling]. AB - WAG rats were exposed to hyperthermia. Neurons manifested acute swelling in all portions of the brain. At the ultrastructural level these phenomena were characterized by an increase in the size of the bodies and nuclei of neurons, complete dissociation of polysomes, swelling of some cisterns of the endoplasmatic reticulum and perinuclear space, and destruction of the mitochondria of apical processes. Hyperchromic (dark) cells were found to be more resistant to acute swelling. The question is discussed whether this pathology of neural cells is reversible. The role of this pathology in the neuropathology of febrile schizophrenia is considered. PMID- 4041106 TI - Estimation of the extent of platination and the sites of Pt binding after interaction of cis- and trans-diamminedichloroplatinum(II) with DNA and chromatin. AB - Differences in the mode of binding of cis- and trans-diamminedichloroplatinum(II) complexes (cis and trans-DDP) with DNA and chromatin were studied with the use of [14C]methylbromphenvinphos as an alkylating agent which attacks the sites in purines bases involved also in the reaction with cis-DDP (Olinski et al., J. Biochem. Biophys. Meth., 7, 171-173, 1983). Methylation of pre-formed DDP-DNA and DDP-chromatin complexes, followed by qualitative and quantitative analysis of the methylation products in DNA hydrolysates, permitted evaluation of the distribution and extent of platination of the bases. No major differences were found between the action of the two DDP isomers on DNA. However, a significant decrease in binding of trans-DDP to adenine moieties was observed when the interaction of cis- and trans-DDP on chromatin was compared. PMID- 4041107 TI - Cyclical mastalgia and breast pathology. AB - Histologic examination of mammary tissue from 39 patients with cyclical mastalgia and 68 with no mastalgia disclosed that fibrocystic disease was not in itself the cause of the cyclical condition. Nor did the study support the traditional concept of a relationship between major dysfunction of the internal genital organs and cyclical mastalgia. Although the organic basis for cyclical mastalgia is unknown, several observations strongly suggest that it is located in the mammary stroma. Future investigations of the organic basis for cyclical mastalgia should include the mammary stroma. PMID- 4041108 TI - Acute intestinal obstruction and splenic hemorrhage due to metastatic choriocarcinoma. A case report. AB - Choriocarcinomas are rare malignancies which occasionally cause acute abdominal symptoms, mainly in the form of hemorrhage. We here describe a patient with metastatic choriocarcinoma presenting as acute intestinal obstruction and splenic hemorrhage. This seems to be the first report in the literature of a choriocarcinoma causing invagination of the small intestine. The abdominal manifestations of the neoplasm are briefly discussed. PMID- 4041109 TI - VIP stimulation of beta-naphthylamidase activity in guinea-pig thyroid sections. AB - Subsequent to the discovery of vasoactive intestinal peptide (VIP) in the thyroid gland, VIP has been shown to stimulate various thyroid functions. The site of interaction of VIP with the thyroid follicular cell is at present not known, and this study has used the ultrasensitive cytochemical bioassay (CBA) for thyroid stimulators to investigate this further. Exposure of thyroid sections for 3 min to VIP resulted in increased naphthylamidase activity, with half-maximal response observed at 3 X 10(-13) M VIP. This response to such low doses of VIP is consistent with the CBA being ultrasensitive to other thyroid stimulators e.g. TSH, thyroid stimulating antibodies and forskolin. The response to VIP was abolished by rabbit anti-VIP antiserum. The dose-response curve to VIP was bell shaped (as with the other stimulators), maximal stimulation occurring at 10(-12) M VIP. In contrast, however, to other thyroid stimulators, namely TSH, LATS-B and 3 monoclonal stimulating antibodies, whose ascending limbs of the dose-response curves extended over 3-4 orders of magnitude, the VIP curve rose rapidly from basal to maximal tissue stimulation from 10(-13) to 10(-12) M VIP, i.e. one order of magnitude. This unusual dose-response curve to VIP was parallel to that produced by forskolin. 11E8, a monoclonal 'blocking' antibody which is a potent inhibitor of TSH stimulation, did not 'block' forskolin stimulation, consistent with the belief that forskolin acts at a post-receptor site.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4041110 TI - Serum somatomedin-C and bioassayable growth-promoting activity (thymidine activity) in appropriate and small-for-gestational-age human newborns. AB - The serum level of radioimmunoassayable somatomedin-C and the bioassayable growth promoting activity evaluated by the stimulating effect of serum upon thymidine incorporation into activated lymphocytes have been measured in the blood of term human foetuses. Comparison between those with a low birth weight and those with normal birth weight has shown that small-for-gestational-age subjects have lower somatomedin-C (0.31 +/- 0.03 vs 0.52 +/- 0.03) and thymidine activity (1.03 +/- 0.11 vs 1.50 +/- 0.07) (P less than 0.001). A positive correlation between somatomedin and thymidine activity was found. There was no difference in serum transferrin levels between both groups. It is suggested that somatomedin, and probably other growth-promoting factors measured by the thymidine bioassay, play a role in regulation of the foetal growth. PMID- 4041111 TI - Problems related to the implantation of the human egg after in vitro fertilization. AB - Egg implantation, the process by which the conceptus comes in contact with the maternal vascular bed, occurs as the consequence of well coordinated ovo endometrial interactions. In this paper the Authors describe the early steps of the implantation process in the rat. Several changes appearing in the rat endometrium are of particular interest because they also appear in the human endometrium around the normal time for implantation. PMID- 4041112 TI - [Immunological and hematological changes in the preleukemic stage of leukemia in Donryu rats induced by N-ethylnitrosourea]. PMID- 4041113 TI - [Effect of sera from patients with aplastic anemia and ITP on murine megakaryocytopoiesis]. PMID- 4041114 TI - Corneal endothelium after photocoagulation in diabetic patients. AB - The corneal endothelium was photographed through a wide-field specular microscope in 38 eyes, in 20 successive diabetic outpatients receiving laser therapy because of underlying proliferative or background retinopathy. Areas of 100 individual endothelial cells from each central cornea were analysed using a digitizer. No statistically significant correlations were observed between mean cell areas or standard deviations of mean and total amount of previous laser energy received. Laser therapy or the type of diabetes did not seem to cause statistically significant changes in the endothelial cell areas examined. PMID- 4041115 TI - Fingerprint-like straight crystalloid microfilaments in lobular glomerulonephritis. AB - This 64-year-old male presented edema and proteinuria. With increasing renal insufficiency and persistent fever, he died 7 months after the onset of illness, complicated with terminal miliary tuberculosis. All the glomeruli showed sclerotic nodular lobulation and mesangial circumferential interposition with positive immunoglobulin and complement predominantly along the capillary, consistent with lobular glomerulonephritis (LGN) or terminal stage of membranoproliferative glomerulonephritis (MPGN). Electron microscopy revealed subepithelial straight crystalloid microfilaments in the amorphous deposits. These structures possibly represent IgG or its fragment as a component of immune complex crystallized in some particular condition. PMID- 4041116 TI - [Ratios between the cell number, surface and volume in the joint cultivation of yeasts--producers of protein]. PMID- 4041117 TI - Intracranial haemostasis with a neurosurgical CO2-laser unit. AB - The authors have been using CO2-laser radiation routinely for more than 2 years. After having recalled the basic thermal properties of this beam, they present their experience. The goal of this work is to point out the particular benefit of CO2-laser cautery to perform tumoral haemostasis. The technical data of this CO2 laser haemostasis are detailed for 3 main indications: In cases of a precise origin of the haemorrhage, the coagulation of small intratumoural vessel necessitates a low output power: 2-4 watts in continued emission; 10-15 watts in the pulsed mode. The beam must be defocussed so as to be as large as the aimed vessel. A micro-manipulatotor is necessary for deeply located tumours. Basal meningiomas, neurinomas, giant adenomas are the best indications. If a diffuse bleeding is encountered in the operative cavity the output must be a little higher: 3-8 watts in continuous mode or 15-30 watts in the pulsed mode; first the cavity is swept with a defocussed CO2-laser ray; then the few larger vessels which have not been cauterized are coagulated one by one either by laser or by bipolar coagulation. The insertion zone of a meningioma can be efficiently coagulated by CO2-laser: a 150-200 watts output in the pulsed mode is necessary if the attachment is dural, a 300-400 watts pulsed output in the case of bony infiltration. PMID- 4041118 TI - Therapeutic experience of advanced urothelial tract tumors. AB - Twenty-three patients with locally advanced and/or metastatic urothelial tumors were treated by surgery, chemotherapy or radiation. Radical operation with or without radiation resulted in tumor free conditions in 8 patients. Fifteen patients who had a few dimensionally estimable disease parameters, underwent chemotherapy. Objective responses were obtained in 6 of the 15 patients (1 CR and 5 PR). The objective response of low grade or low stage tumors or cases with high Karnofsky performance ratings was moderate. Combination chemotherapy with cisplatin (CDDP), doxorubicin (ADM) and cyclophosphamide or a CDDP-containing combination appeared to be beneficial for patients with advanced urothelial tract tumors with palliative purpose. PMID- 4041119 TI - [A case of primary malignant lymphoma of the urinary bladder]. AB - This paper presents an autopsy case of primary malignant lymphoma of the urinary bladder. The patient, a 63-year-old man, consulted us because of macroscopic hematuria. Cystoscopy revealed a bladder tumor, which was diagnosed as an anaplastic cell carcinoma by transurethral punch biopsy. The tumor progressively increased in size, despite treatment with preoperative antineoplastic chemotherapy consisting of CDDP. Only ureterocutaneostomy and biopsy were performed at the operation although total cystectomy and ileal conduit had been planned, because the tumor had invaded into the perivesicular tissue. Biopsy revealed B cell lymphoma, which was characterized by specific staining with IgG by the PAP method. Although antineoplastic chemotherapy was performed again after operation, the patient gradually weakened and died 5 months after admission. At autopsy, a hen-egg sized, non-papillary tumor which invading into the perivesicular tissue was found at the anterior wall of the urinary bladder. There were many metastatic nodules in the thraco-lumbar vertebral columns, para-aortic lymphnodes and mesenteric lymphnodes. Lungs and liver were free from metastatic tumors. PMID- 4041120 TI - On contagious ecthyma and its treatment in muskoxen (Ovibos moschatus). PMID- 4041121 TI - Vaccination against ringworm of calves in specialized beef production. PMID- 4041122 TI - Possibility of 2,4,5-triamino-6-hydroxypyrimidine as an intermediate in the pathway of riboflavin biosynthesis. AB - It was studied with resting cells of a high flavinogenic mold, Eremothecium ashbyii, whether or not 2,4,5-triamino-6-hydroxypyrimidine (THP) is an intermediate in the early pathway of riboflavin biosynthesis. A small amounts of THP strongly inhibited riboflavin formation in the resting cells, but the inhibition was effectively reversed by the added purines, except for adenine. Radioactive tracer experiments showed that the incorporation of the radioactivity from [2-14C]THP into riboflavin was negligible. The results obtained strongly suggest that THP is not an intermediate but a rigid inhibitor for riboflavin formation, and thus there is non salvage pathway of THP for the pathway of riboflavin biosynthesis in resting cells of E. ashbyii. PMID- 4041123 TI - Studies on the 4-carbon compound needed for the formation of the O-xylene ring of riboflavin. AB - The 4-carbon compound necessary for the formation of the o-xylene ring of riboflavin, was examined using labeled glucose and diacetyl in resting cells of Eremothecium ashbyii. The specific activity-time curves of riboflavin and lumichrome in the tracer experiments with [U-14C] glucose indicated that the specific activity of riboflavin during the incubation is much higher than that of its photolytic product, lumichrome. It is far above the level expected if the ribityl moiety of an intermediate, 4-ribitylamino-5-amino-2,6-dihydroxy pyrimidine (RAADP), was to be utilized as the source of the 4-carbon unit on the o-xylene ring of riboflavin. It was further demonstrated that the specific activities of diacetyl and lumichrome at 10.5 h of the incubation and those of crystalline riboflavin and lumichrome at the later stage (20 h) of the incubation were identical respectively. Radioactive diacetyl furthermore proved to be likewise incorporated with a two fold dilution into riboflavin and lumichrome at 17 h of the incubation. The results reveal that it is not the ribityl fragment of RAADP bu the diacetyl that is the 4-carbon unit for the formation of the pyrazine ring of 6,7-dimethyl-8-ribityllumazine, that is, the o-xylene ring of riboflavin in the mold of Eremothecium ashbyii, although we still do not know whether the diketone requiring reaction is enzymatic or non-enzymatic. PMID- 4041124 TI - Ischemic heart disease: part of the premenstrual syndrome? PMID- 4041125 TI - Chemotherapy of metastatic primary cardiac sarcomas. PMID- 4041126 TI - Transient Q waves during exercise in hypertrophic cardiomyopathy. PMID- 4041127 TI - Influence of dietary cis- and trans-fat on 1,2-dimethylhydrazine-induced colon tumors and fecal steroid excretion in Fischer 344 rats. AB - To investigate the effects of the difference in the geometry of dietary fatty acids on colon tumorigenesis, male rats were fed semipurified diets containing either partially hydrogenated corn oil (trans-monoene fat) or olive oil (cis monoene fat) at the 10% level and received a single oral dosage of 1,2 dimethylhydrazine (DMH). The difference in the fatty acid composition of dietary fats was confined essentially to the geometrical isomerism of octadecenoate, and the linoleic acid content was made equivalent (2% of total energy). After about 15 mo of feeding, colon tumor incidence in DMH treated rats was nearly the same in both fat groups. Fecal neutral steroid excretion was higher, while the transformation of cholesterol to coprostanol was lower in rats given the trans fat. There were no marked differences in the excretion and composition of fecal bile acids between two fat groups. Serum cholesterol and tocopherol levels of rats given trans-fat diets tended to be low. The results suggested that the trans monoene behaves much like the cis-monoene in the incidence of DMH-induced colon tumors, although there were characteristic differences in metabolic events in the intestine. PMID- 4041128 TI - Vitamin B6, vitamin C and folacin levels in milk from mothers of term and preterm infants during the neonatal period. AB - Studies of the composition of milk from mothers who deliver prematurely have focused primarily on macronutrients and trace elements while its vitamin composition has received little attention. This study focused on vitamin B6, vitamin C and folacin in preterm (PT) and term (T) milk which are critical to early growth and development. Fifteen PT and twelve T mothers were studied for five 24-h periods during the first month of lactation. Vitamin C levels were higher in PT milk during the first week of lactation whereas folacin levels were similar to T milk. Vitamin B6 levels in PT milk were lower than in T milk throughout the first month postpartum. These findings suggested that the use of PT milk as the sole source of these nutrients is open to question and that during the neonatal period PT infants need supplements of certain micronutrients. PMID- 4041129 TI - The pathology of the spleen in steroid-treated immune thrombocytopenic purpura. AB - The spleen is a central organ in the pathophysiology of immune thrombocytopenic purpura (ITP). Splenic lymphoid tissue synthesizes anti-platelet IgG, and splenic cordal macrophages destroy platelets coated with anti-platelet antibodies. The morphologic features of the spleen in this disease reflect this splenic function: hypertrophied lymphoid follicles with secondary germinal centers in the white pulp, with perivascular plasma cells in the red pulp and evidence of increased platelet phagocytosis in cords of the Billroth. Foamy macrophages and evidence of a variable degree of extramedullary hematopoiesis also have been noted. The authors have studied 17 spleens removed for therapeutic purposes in patients with proven ITP previously treated with varying amounts of corticosteroids. In all cases there was little or no morphologic evidence of follicular hyperplasia or plasmacytosis. However, platelet sequestration and phagocytosis were demonstrated easily in all cases, both in histologic sections and in touch imprints. The authors' findings indicate that morphologic evidence of lymphoid activation characteristic in spleens from patients with ITP usually is ablated by prior corticosteroid therapy but that the characteristic platelet sequestration and phagocytosis persists. PMID- 4041130 TI - Cryptosporidiosis outbreak in a day-care center. AB - An outbreak of diarrhea occurred in a day-care center in San Marcos, Tex, in August 1984. At the time of this study, the center was caring for 81 children aged 2 months through 5 years. A single stool specimen was collected from each of 50 children (62%). Cryptosporidium oocysts and Giardia lamblia cysts were each identified in stool specimens from 18 children. Three children had both parasites present in the same stool specimen. Echovirus 30 was identified in 19 of 25 stools cultured. Although three pathogens were circulating simultaneously in this group of children, only the presence of Cryptosporidium oocysts was associated with the occurrence of a diarrheal illness. Cryptosporidium may be a common cause of diarrhea in children who attend day-care centers. PMID- 4041131 TI - Radiological case of the month. Osteopenia, rickets, and fractures in preterm infants. PMID- 4041132 TI - Spontaneous resolution of cryptosporidiosis in a child with acquired immunodeficiency syndrome. PMID- 4041133 TI - Gastrointestinal manifestations of the acquired immunodeficiency syndrome: a review of 22 cases. AB - Patients with acquired immunodeficiency syndrome (AIDS) frequently have diarrhea and weight loss. We prospectively examined the upper and lower gastrointestinal tracts in 22 AIDS patients, although severe medical problems often precluded full evaluation. Ninety-six percent (21 of 22) lost weight, and 55% (12 of 22) had diarrhea. The mean (+/- SD) weight loss was 34 +/- 19 lb. Steatorrhea was found in 4 of 14 patients, and D-xylose tests were abnormal in 8 of 14 patients. Mean serum albumin was 3.3 +/- 0.8 g/dl. A significantly diminished plasma selenium level, which can influence immune function, was noted in these AIDS patients. Gastrointestinal infections were identified in 45% of patients. Although diarrhea and malabsorption were more common in the infected group, weight loss and albumin were similar in those with and without demonstrated infections. Flexible sigmoidoscopy showed that of 15 patients, there were two with Kaposi's sarcoma, 10 normals, and three with nonspecific endoscopic changes of colitis. Infection was documented in all patients with colitis. Panendoscopy of the upper gastrointestinal tract was positive for AIDS-related pathology in five of 10 patients, including two with Kaposi's sarcoma, one with Candida esophagitis, one with herpetic esophagitis, and one with gastroduodenitis (biopsy positive for cryptosporidia); five patients had a normal-appearing tract. Small bowel or colonic biopsies frequently showed nonspecific inflammatory changes, although pathogens were identified in six patients (27% of all biopsies). We conclude that a wide variety of gastrointestinal pathology, which includes infectious agents, neoplasms, and inflammatory changes, may occur in AIDS patients. Therefore, AIDS patients, particularly those with diarrhea or weight loss, deserve an intensive evaluation for remediable lesions of their gastrointestinal tracts. PMID- 4041134 TI - Thrombotic thrombocytopenic purpura syndrome in systemic lupus erythematosus: treatment with plasma infusion. AB - Two patients with well documented systemic lupus erythematosus developed a syndrome resembling thrombotic thrombocytopenic purpura. Both had severe thrombocytopenia, microangiopathic hemolytic anemia, seizures, and renal dysfunction. Prothrombin time, partial thromboplastin time, thrombin time, and fibrinogen levels were normal; fibrin degradation products were minimally elevated. Histologic evaluation of renal biopsies in both patients confirmed the impression of intravascular thrombosis. Therapy with corticosteroids, other immunosuppressive drugs and splenectomy (in one case) proved unsuccessful. The infusion of fresh frozen plasma, with or without plasmapheresis, reversed the syndrome. This report indicates that patients with systemic lupus may develop a thrombotic thrombocytopenic purpura like syndrome which responds to fresh plasma infusion. PMID- 4041135 TI - Continuing a clinical pharmacokinetic dosing service under prospective pricing. PMID- 4041136 TI - Comparison of the intraperitoneal and intravenous routes of cisplatin administration in an advanced ovarian cancer model of the rat. AB - A model of human advanced ovarian cancer was made by intra-abdominal inoculation of a cloned ovarian adenocarcinoma cell line of the Sprague-Dawley rat (ROT68/C1) into isologous newborn rats. Intra-abdominal tumors and tumors metastatic to the lung developed in 100% of the animals within 3 weeks after inoculation. With use of this model the intraperitoneal and intravenous routes of cisplatin (cis diamminedichloroplatinum) administration were compared with regard to both the pharmacokinetics and the antitumor activity. After 2 hours of administration the serum cisplatin values were greater following use of the intraperitoneal route than with use of the intravenous route. Cisplatin values in the intra-abdominal tumor tissues were greater after the intraperitoneal route of administration than the intravenous route, and the growth was suppressed more prominently after intraperitoneal administration. No difference in drug values in the kidney tissues was found between the two administration routes. Thus the intraperitoneal route of cisplatin administration seems to be much more effective against advanced ovarian cancer confined to intra-abdominal cavity than does the intravenous route. PMID- 4041137 TI - Influence of ovarian steroids on prostaglandin- and leukotriene-induced uterine contractions. AB - The mammalian uterus is capable of metabolizing arachidonic acid via the lipoxygenase pathway, and the uterus responds to lipoxygenase products. We postulated that progesterone influences the production of leukotrienes in the uterus in a way similar to that in which estradiol influences prostaglandin production. Uterine contractions were measured in actively sensitized guinea pigs throughout the estrous cycle and in ovariectomized, hormonally primed, sensitized guinea pigs. Antigen challenge stimulated uterine contractions (caused by prostaglandins) that increased throughout the estrous cycle to a maximum in day 15, when estradiol is at its peak. Pretreatment with indomethacin abolished uterine contractions except on day 9 of the cycle, when progesterone levels are at their highest. Day 9 contractions were blocked by FPL 55712, a selective receptor antagonist of leukotrienes. These findings were confirmed in ovariectomized/sensitized guinea pigs. Our data suggest that endogenous synthesis of leukotrienes in the uterus may be directly related to the rise of progesterone. PMID- 4041138 TI - Management of autonomic hyperreflexia associated with a low thoracic spinal cord lesion. AB - Autonomic hyperreflexia is a serious peripartum complication associated with spinal cord lesions. Although the majority of reported cases have occurred with lesions at T-5 or higher, we report a case occurring in a patient with a lesion at T-10. Management may be by regional anesthesia or primarily medical. PMID- 4041140 TI - [Effect of 2 new GABA-ergic agents on apomorphine stereotypy in the rat]. PMID- 4041139 TI - Effects of single and repeated application of clonazepam and diazepam combined with cyproheptadine on apomorphine stereotypy in rats. PMID- 4041141 TI - [2 new GABA-ergics (GABA-linoleamide and GABA-steatamide). On 2 experimental models of depression]. PMID- 4041142 TI - Diagnosis and immunotherapy of mould allergy. II. Reproducibility and relationship between skin sensitivity estimated by end-point titration and histamine equivalent reaction using skin prick test and intradermal test. AB - To determine reproducibility and the optimal way of expressing skin sensitivity, simultaneous skin prick tests (SPT) and intradermal tests (ICT) were performed on 25 mould-allergic patients. The patients had a well-documented history of allergy to Cladosporium and Alternaria and were tested with partially purified standardized extracts of these two mould species. Skin prick tests were carried out on the volar side of the forearm and intradermal tests on the backs of the patients. The skin tests were performed as titration using quadruplicate determinations of 10-fold allergen dilutions. The area of the skin reactions measured by planimetry were plotted in a log-log system as a function of the allergen concentration. The reproducibility (SD/mean area X 100%) of the ICTs was significantly higher than that of the SPTs (17% versus 29%). A very low reproducibility was found with wheal areas less than 5 mm2. The dose response curve of the SPT wheal area was steeper than that obtained with ICT, both concerning ICT wheal and flare. Increasing the allergen concentration with a factor 10 resulted in a doubling of the wheal area in SPT, in contrast to a factor 1.7 using ICT. The coefficient of correlation using linear regression on the dose response curve was always higher than 0.9 with SPT and ICT wheal, but significantly lower with ICT flare. Skin sensitivity was estimated as end-point and histamine equivalent reaction. No significant correlation between SPT and ICT end-point titration was found contrary to the histamine equivalent reaction.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4041143 TI - [Quantification of immunoglobulins and complement system factors in secretory otitis media]. PMID- 4041144 TI - Biological and immunological characteristics of 125I-4Tyr and -18Tyr Escherichia coli heat-stable enterotoxin species purified by high-performance liquid chromatography. AB - A rapid procedure for the separation of Escherichia coli heat-stable enterotoxin iodination products is described. A two-step procedure using reverse-phase chromatography results in the separation of native, noniodinated heat-stable enterotoxins from several distinctly iodinated species which differ in their ability to bind to brush border receptors. Sequence analysis of the radioligands demonstrated mutually exclusive labeling at the 4Tyr and 18Tyr residues. These tracers have been immunologically and biologically characterized and have been shown to be antigenically similar but to differ in their toxicity for suckling mice. The radioligands separated by this procedure demonstrate stable behavior for a period of months. PMID- 4041145 TI - Tanycytes in the medial habenular nucleus of the rat. AB - Tanycytes with foot processes contacting capillary basal membranes were identified in the rat medial habenular nucleus. They constitute a relatively small but constant population of cells among the conventional ependymal cells. In contrast to tanycytes in most circumventricular organs, habenular tanycytes possess cilia. Superimposed upon the cells are nerve fibers belonging to the serotonergic supraependymal axon plexus. Their ultrastructure differs in many respects from that of hypothalamic tanycytes. PMID- 4041146 TI - Verapamil potentiation of neuromuscular blockade: failure of reversal with neostigmine but prompt reversal with edrophonium. PMID- 4041147 TI - Sheep twin chimaeras with admixtures of red cell amino acid and potassium transport phenotypes. AB - A pair of sheep twins each had two populations of red cells. Population 1 was positive for antigens Aa, Ma and Mb, was low-potassium type, possessed an amino acid transport system and was lysine-negative phenotype. Population 2 was negative for antigens Aa, and Mb, was high-potassium type, lacked the amino acid transport system and was lysine-positive phenotype. Population 2 disappeared from both sheep over a period of 8 years. PMID- 4041148 TI - Cytoplasmic estrogen and progesterone receptors in canine endometrium during the estrous cycle. AB - Estradiol and progesterone receptors (ER, PR) were characterized and measured in cytosols from canine endometrium, using saturation and sucrose-gradient centrifugation radioassays. Both receptors were demonstrated to be steroid- and tissue-specific saturable proteins, which bound the respective steroids with high affinity (dissociation constant [Kd] approximately 10(-9)M). Serum estradiol, progesterone, and endometrial cytosol receptor concentrations and receptor binding affinity were measured for 25 bitches from which samples were obtained at 5 stages of the estrous cycle (5 bitches each): anestrus (A), the 3rd day of proestrus (P3), the 3rd day of estrus (E3), the 12th day after onset of estrus (E12), and the 28th day after onset of estrus (E28). Mean (+/- SEM) serum estradiol concentrations were 17.0 +/- 2.2 (A), 55.4 +/- 5.0 (P3), 89.4 +/- 24.9 (E3), 41.0 +/- 5.9 (E12), and 50.6 +/- 3.9 (E28) pg/ml. Mean (+/- SEM) serum progesterone concentrations were 0.4 +/- 0.1 (A), 1.5 +/- 0.2 (P3), 17.3 +/- 7.5 (E3), 41.6 +/- 9.5 (E12), and 25.8 +/- 3.2 (E28) ng/ml. Concentrations of ER increased significantly from 1.06 pmol/g of uterus during stage A to a peak concentration of 6.18 pmol/g of uterus at E12, followed by a gradual decrease to 0.69 pmol/g of uterus by E28. The PR concentrations increased from 3.01 pmol/g of uterus in stage A to 17.32 pmol/g of uterus at P3; PR concentrations, thereafter, decreased gradually to 1.85 pmol/g of uterus by E28. Dissociation constants were significantly higher at E12 for the ER (Kd = 2.6645 X 10(-9)M) and at P3 for the PR (Kd = 5.8282 X 10(-9)M) than at the other stages examined, indicating a decrease in receptor affinity during the periods of high receptor concentrations.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4041149 TI - Local pulmonary immune responsiveness after multiple antigenic exposures in the cynomolgus monkey. AB - Two cynomolgus monkeys were immunized with sheep red blood cells in the right diaphragmatic lobe (RD) 4 times, 20 days apart. At the time of the fourth immunization, the left diaphragmatic lobe (LD) was also immunized. There were increases in both IgM anti-SRBC antibody-forming cells (AFC) and specific IgG in the RD lobe after each successive challenge. In the fourth challenge, the RD had an increase in anti-SRBC AFC 10-fold that of the LD lobe. The concentration of specific IgG was also higher in the RD lobe. With total protein as an indicator of vascular permeability, the LD had a greater increase in vascular permeability than did the RD. These data suggest that the increased immune responsiveness of the RD after multiple challenges was in part locally derived rather than entirely caused by increased recruitment of immune cells and antibody from the blood. PMID- 4041151 TI - [Primary malignant tumors of the heart. Anatomo-clinical study of 12 cases]. AB - Five of the 12 cardiac sarcomas reviewed in this study were recruited from 7,200 autopsy studies, including 2,980 performed on patients dying from malignant disease (overall incidence of 0.07 p. 100; 0.16 p. 100 in the group with malignant disease). These tumours are fifty times less common than cardiac metastases which were observed in 12.5 p. 100 of patients in the group with malignant disease. The other 7 cases of cardiac sarcoma were recovered from our surgical pathology archives over a 16 years period. The sarcomas were of the following histological types: angiosarcoma (6 cases), rhabdomyosarcoma (3 cases), fibrosarcoma (2 cases) and mesothelioma (1 case). The clinical presentation was very variable. The diagnosis was often made only at surgery or autopsy. The prognosis was very poor, the majority of patients dying of cardiac constriction or visceral metastases, within one year of diagnosis. PMID- 4041150 TI - Effect of age on antibody responses after lung immunization. AB - The effects of age on the number of lymphoid cells producing specific IgM antibody (AFC) and the level of specific IgM, IgG, and IgA antibody after lung immunization were evaluated in groups of dogs 2 through 16 yr of age. A trend for lowered antibody responses in blood was observed with increasing age, and significantly lowered antibody responses were measured in lavage fluids from immunized lung lobes of older dogs. Statistical evaluations indicated that the lowered antibody responses in the lung were due in part to the reduced AFC and level of specific antibody in the blood. However, a less intense inflammatory response to antigen instilled into the lungs of older dogs also significantly contributed to the lowered antibody responses in their lungs. Additional studies are needed to determine if the loss of inflammation and antibody responses in the lungs of aged dogs increases their susceptibility to pulmonary infections. PMID- 4041152 TI - [Perinatal mortality: clinico-statistical considerations (1970-1981)]. PMID- 4041153 TI - [Experimental study of the ototoxicity of cisplatinum]. AB - Cisplatinum, used in numerous multiple chemotherapy regimens, provokes cochleovestibular toxicity. Two series of rats were treated with single or increasing fractionated doses, and audiometric consequences evaluated from modifications in auditory evoked potentials from brain stem and from electrocochleographic recordings. The ototoxic effect was found to be dose related with a cumulative effect. Fractionated doses were less ototoxic than single doses. The mechanism of production of this ototoxicity has not been determined but is probably similar to that of the aminoglycosides. PMID- 4041154 TI - [Kasabach-Merritt syndrome in infants. 2 cases]. AB - Two infants presenting with Kasabach-Merritt syndrome point out several points: the hemangioma may look innocuous with small proportions. The coagulopathy may be represented by a simple thrombopenia or an intravascular coagulation (PDF, ethanol test) of bad prognosis. A review of 150 observations of Kasabach-Merritt syndrome suggests a simple therapeutic approach: corticotherapy (2 to 4 mg/kg) for 2 to 4 weeks or, if failure, antiaggregant drugs. Radiotherapy is proposed in cases of emergency. Heparin and antifibrinolytic treatments are restricted to cases with severe coagulopathy. PMID- 4041155 TI - [Hepato-erythrocytic porphyria in 2 female twins]. PMID- 4041156 TI - Plasma free testosterone--is an index sufficient? AB - Only about 50% of women who are clinically hirsute have a raised total plasma testosterone concentration; in those cases where the total testosterone is normal the free testosterone may, in fact, be raised. Since the measurement of free testosterone is tedious, workers have used an androgen index or a calculated free testosterone concentration from the measurements of total testosterone and sex hormone-binding globulin. We have examined the correlation between measured free testosterone, a derived free testosterone and an androgen index in hirsute women, normally menstruating women and non-hirsute women on oral contraceptive therapy. These three measures of the free testosterone concentration in blood gave similar results in all cases. PMID- 4041157 TI - Argon laser photocoagulation in diabetic retinopathy: five year review of 697 treated eyes. AB - Diabetic retinopathy has now become a common cause of blindness in Singapore. Fortunately, laser photocoagulation has prevented blindness in the majority of patients who were treated. An analysis of 872 patients treated with argon laser photocoagulation showed that 424 patients (48.6%) were for diabetic retinopathy. Patients with adequate treatment retained useful vision. Those who lost vision frequently had associated target organ involvement besides inadequate laser treatment. Patients with proliferative diabetic retinopathy were treated with peripheral retinal photocoagulation. Patients with diabetic maculopathy especially those with focal leaks were treated with localised photocoagulation. A common cause of blindness is failure to recognise the condition early. Physicians and general practitioners must, in the management of diabetics, examine their patients periodically with the pupils dilated in a darkened room. PMID- 4041158 TI - Assessment of the cause of infertility. AB - The different causes of infertility and evaluation of the infertile couple are reviewed in this paper. Forty to 50 percent of cases are due to male factors, and special emphasis is placed in describing techniques to diagnosis this type of infertility. Five to ten percent of infertile couples have infertility of unknown etiology even after a complete, appropriate evaluation. Special instruction in how to diagnose and treat these types of patients is described. A step by step evaluation of peritoneal factors, ovulation factors, and male and cervical mucus interaction is presented for the clinicians' use. PMID- 4041159 TI - Path analysis of family resemblance for cranio-facial traits in Andhra Pradesh nuclear families and twins. AB - Path analysis of 12 cranio-facial measurements from a sample of nuclear families and twins from Andhra Pradesh, India is used to test hypotheses about the familial transmission of these traits. For bigonial breadth and ear dimensions, the transmission from parent to child is consistent with simple autosomal polygenic inheritance, but length, breadth and circumference of the head, facial breadth and nose dimensions show evidence of transmission in excess of polygenic expectations. Additional non-transmissible resemblance of sibling pairs is not significant for any of the variables, but twin pairs do exhibit significant additional resemblance for head circumference, head length, minimum frontal breadth, bizygomatic breadth and ear dimensions. The effect of interobserver measurement differences can be detected for head breadth, minimum frontal breadth, bigonial breadth, total facial height and nose dimensions. PMID- 4041160 TI - Sequential measurement of intratumoral platinum concentration in cervix uterine tumors after cis-dichlorodiammineplatinum (CDDP) administration. AB - Intratumoral (cervix uterine tumors) distribution of platinum was studied in ten patients after IV administration of CDDP. Sequential tumoral measurement of platinum was carried out 4, 24, and 48 h after the IV infusion. Platinum concentration in the tumor samples ranged from 0 to 29,5 ng/mg tissue. For all patients, there was no definite evolution of the tumoral concentration with time and there was no good relation for the same patient between the platinum concentration in three successive biopsies. These results involve uncertainty in studies attempting to relate CDDP tumor levels (measured in one biopsy) and tumor response to chemotherapy. PMID- 4041161 TI - Heterogeneity of cell lines derived after transformation of early passage rodent cells by the Ha-ras1 human oncogene. AB - The chromosome patterns of Chinese hamster cell lines derived after immortalization or tumorigenic conversion of early passage cells with recombinants carrying the mutated T24 or the normal human Ha-ras1 gene have been characterized by trypsin-Giemsa banding. Whereas immortalized Chinese hamster cell lines exhibited a near normal karyotype, tumorigenic cell lines were found to have abnormal karyotypes carrying marker chromosomes. Moreover, chromosomal patterns correlated with growth in semisolid media and tumourigenicity in nude mice. Similarly, malignant conversion of early passage Syrian hamster cells, with a recombinant carrying the mutated T24 human Ha-ras1 gene, resulted in cells with a near diploid karyotype. On the other hand, tumorigenic conversion of early passage Wistar rat cells with the same oncogene produced cell lines with heteroploid karyotypes. More chromosomal alterations have been observed during further growth of these cells. It is suggested that the transformed phenotype in these cells may be dependent on the chromosomal instability. PMID- 4041162 TI - Cerebral cortical function in infants at risk for sudden infant death syndrome. AB - Cerebral cortical function was prospectively examined by electroencephalography (EEG) in 3 subgroups of 257 infants at risk for sudden infant death syndrome (SIDS). Group 1 consisted of apparently healthy infants with near-miss SIDS episodes; Group 2 consisted of siblings of SIDS victims; and Group 3 consisted of neurologically suspect infants with apnea. The usual abundance and distribution of sharp EEG transients (SETs) were determined from 69 Group 1 infants. EEGs were interpreted as abnormal in the presence of ictal apnea, excessively abundant SETs, or immaturity of EEG background for conceptional age. Ninety percent of infants in Group 1 had entirely normal EEGs. There was no significant difference in the abundance or distribution of SETs between infants with normal breathing patterns and those with excessively periodic respirations. Nonictal apnea was recorded in 7% of Group 1 infants. The unexpected diagnosis of ictal apnea was confirmed in 2 Group 1 infants (1.2%), and 5 (2.9%) had excessive SETs but no recorded seizures. Only 4 infants (2.3%) had abnormally immature EEGs for conceptional age. Nonictal apnea occurred in 5 of 33 (15.2%) Group 3 infants and ictal apnea was confirmed in 2 others (6.1%). We conclude that the majority of Group 1 and 2 infants have normal cerebral cortical activity between and during apnea and that central nervous system cortical immaturity, as measured by EEG, plays no important role in the pathogenesis of SIDS. SETs are commonly recorded in these infants and must be conservatively interpreted. However, an EEG examination was critical in establishing the unexpected diagnosis of ictal apnea in a small percentage of Group 1 and 3 infants and materially influenced subsequent evaluation, management, and prognosis. PMID- 4041163 TI - Purification and properties of an endo-alpha-mannan hydrolase from the mushroom Volvariella volvacea. AB - The enzyme, endo-alpha-mannanase, from culture filtrate of a mushroom Volvariella volvacea has been purified 73-fold by acetone precipitation, ion-exchange chromatography (DEAE-Sephadex), and gel-permeation chromatographies on Bio-Gel P 300 and on Sephacryl S-200 columns. The enzyme preparation gave a single protein band on sodium dodecyl sulfate-disc gel electrophoresis at pH 6.8 and has a molecular weight of approx. 56,000. It has no alpha- or beta-mannosidase activity and does not act on beta-gluco-or galactomannan. The enzyme shows maximum activity on baker's yeast alpha-mannan at pH 5.0 and at 55 degrees C, and is fairly stable between pH 3 and 6 and temperatures up to 50 degrees C. The Km is 32.25 mg mannan/ml. Enzyme activity is inhibited by Hg2+, sodium azide, iodoacetic acid, EDTA, and Ag+, in decreasing order. PMID- 4041164 TI - [A case of remission in diffuse pleural mesothelioma induced by anticancer chemotherapy with cisplatin and adriamycin]. AB - A 56-year-old man was admitted to our hospital with complaints of dyspnea and right pleural effusion. Malignant pleural mesothelioma was diagnosed, based on the high level of hyaluronic acid in the pleural fluid and manifestation of malignant cells by pleural needle biopsy. Anticancer chemotherapy with cisplatin and intrapleural injections of adriamycin against this mesothelioma was carried out because of the presence of stage III by Butchart's classification. Regression of the tumor, decrease of pleural fluid and decrease of LDH level in effusions were observed after this chemotherapy. Cisplatin was easily transported into the pleural fluid, and its concentration was maintained for a satisfactorily long period. PMID- 4041165 TI - [Complete remission of bladder cancer with multiple pulmonary metastases obtained by combined chemotherapy with cis-platinum, adriamycin and cyclophosphamide]. AB - A 54-year old man with metastatic transitional cell carcinoma (grade 3) of the bladder has achieved complete remission as a result of combination chemotherapy. Plain chest X-P demonstrated multiple pulmonary metastases and computed tomography demonstrated a 35 X 40 mm-sized bladder tumor. The patient was treated with four courses of combination chemotherapy consisting of cis-platinum, adriamycin and cyclophosphamide, after which complete disappearance of the pulmonary metastases and bladder tumor was observed. The patient has been followed up, with no evidence of tumor nine months after the treatment. PMID- 4041166 TI - [Pharmacokinetics of non-protein bound platinum formed from cisplatin]. PMID- 4041167 TI - Stanozolol in the treatment of pityriasis rubra pilaris. PMID- 4041168 TI - [Report of 3 cases of specific type cancer of the upper gastrointestinal tract adenosquamous cell carcinoma of the esophagus, choriocarcinoma of the stomach and squamous cell carcinoma of the stomach]. PMID- 4041169 TI - Myenteric enkephalin neurons around the laser-photocoagulation necrosis: an immunocytochemical investigation in the guinea pig jejunum and proximal colon. AB - Laser irradiation-caused features of neuronal regrowth containing enkephalin-like immunoreactivity in the myenteric plexus around the necrosis were investigated in the guinea pig jejunum and proximal colon using an antiserum to methionine enkephalin-Arg6-Gly7-Leu8. The power level and irradiation time of the argon laser beam were adjusted to make a coagulation spot of about 0.5 mm in diameter. A distinct accumulation of the immunoreactivity occurred in the laser photocoagulated ends of the enkephalin neuron processes. Regeneration of the severed axon-like process took place in the following order: swelling and budding at the severed proximal end; elongation and branching of newly-formed nerve fibers; and formation of a tangled overgrowth. Approximately 43-90 hrs after the laser microsurgery, immunoreaction of the enkephalin neuron perikarya was stronger in the first several rows of ganglia, on both the oral and anal sides of the laser necrosis. In the jejunum, an increase in the intensity of the immunoreaction was more prominent on the oral side than on the anal side, whereas the proximal colon displayed an opposite state. In the jejunum, the anally directed axon-like process of the enkephalin neurons transported a larger amount of the immunoreactivity as compared with the orally-directed wing-ramuli. This paper seeks to prove that the laser irradiation combined with immunocytochemistry may provide a simple and reliable methodology for the study of the projections of enteric neurons. PMID- 4041170 TI - We must stop selling cancer to our children. PMID- 4041171 TI - Patterns of use and incidence of smokeless tobacco consumption in school-age children. AB - A sample of 5,392 students were surveyed using a 42-item, multiple-choice questionnaire from a population of 19,040 Texas school-age children. The geographic distribution was 70% urban and 30% rural, with a representative sampling of the various racial and ethnic groups within Texas. The results of the survey indicated that 486 (9%) of the students regularly used smokeless tobacco, 810 (15%) regularly smoked cigarettes, and 4,096 (76%) used no tobacco products. Further, 77% perceived cigarette smoking as very harmful, while only 40% perceived smokeless tobacco as very harmful. Age of initiating use indicated that 55% of smokeless tobacco users started before the age of 13 years, whereas only 36% of cigarette smokers began that early. PMID- 4041172 TI - A study of mucus glycoproteins in secretory otitis media. AB - Rheologically active mucus glycoproteins (mucins) were isolated from the middle ear effusions of 282 patients (344 ears) with secretory otitis media. Middle ear mucins from those patients with no other associated pathology were compared biochemically and biophysically with mucins from patients where a specific associated pathology was present. The most striking biochemical variation was total carbohydrate content, which was lowest for mucins derived from purulent secretions in general (30.9%) and mucoid secretions from patients with cleft palates (32%). Furthermore, the carbohydrate content was correlated with the rheologic activity of reconstituted mucins, both in dilute solution and in the gel state. All mucins had high intrinsic viscosities, sensitive to ionic strength and the mucolytic N-acetylcysteine. Transport studies indicated that certain middle ear effusions, particularly those from patients with cleft palates, may not be cleared from the middle ear because of insufficient viscoelasticity. PMID- 4041173 TI - Cisplatin-induced ototoxicity: audiometric findings and experimental cochlear pathology. AB - Twenty-four (48%) out of a group of 50 patients treated with one to three single doses of cisplatin compound (cis-DDP), at a dosage of 60 mg/m2 body surface, were found to have deterioration of post-treatment pure tone audiometric threshold levels. Statistical analysis of pre- and post-treatment hearing losses by means of the paired t-test, however, did not show any significant hearing loss associated with cis-DDP-toxicity, nor could hearing loss following treatment be correlated to ages of the patients, pre-treatment hearing impairments, specific frequencies, or the number of treatment courses given. In contrast, cochlear damage was studied in the guinea pig model by daily administration of high cumulative doses of cis-DDP, and was found to be dose-dependent and selectively restricted to the outer hair cells of the inner ear and corresponding nerve fibers. Hair cell degeneration was most severe in the basal turn of the cochlea, and progressed in an apical direction so that the cells in the first row were the most affected. PMID- 4041174 TI - Microcapsule chemoembolization for head and neck cancer. AB - Cisplatin (CDDP) was microencapsulated with ethylcellulose, and microcapsules (CDDP-mc) were infused into the maxillary arteries of patients with various head and neck carcinomas. We then found that the CDDP level in the circulating blood was significantly lower than that in patients administrated intravenous non excapsulated CDDP. However, significantly high concentrations of CDDP were found in the tissues of patients treated with CDDP-mc. Our results suggest that selective arterial infusions of CDDP-mc can exert an intensive topical antitumor effect through microinfarction of malignant tissues. The prolonged release of drug from the microcapsules has also been associated with minimal systemic side effects. PMID- 4041175 TI - Sequelae of ventilation tubes following tonsillectomy. AB - The insertion of middle ear ventilation tubes results in persistent scarring in a significant number of the tympanic membranes incised. The present study was done in order to compare the occurrences of tympanic membrane sequelae following ventilation tube insertions in a group of patients with intact tonsils with that of a tonsillectomized group. The study population had been treated with ventilation tubes 3-5 years previously because of middle ear effusions. A total of 104 patients were re-examined (follow-up rate, 85%). Otomicroscopy was performed by examiners who had no prior knowledge of the patient's past history of ear disease or treatment. The results were categorized by a simplified scoring system. It was found that 60% of the tympanic membranes showed pars tensa abnormalities outside the previous site of the tube. The occurrence of pars tensa tympanosclerosis was more prevalent in tonsillectomized patients. This latter observation is probably a secondary occurrence. However, the high incidence of sequelae following insertions of ventilation tubes calls for their restricted usage. PMID- 4041176 TI - Change of catecholamine turnover in ovary during the rat estrous cycle. PMID- 4041177 TI - Congenital rubella syndrome in Western Australia. AB - The birth prevalence of congenital rubella syndrome (CRS) in Western Australia has been around 20 per 10 000 live births with peaks up to 100 per 10 000 in rubella epidemic years. The rate appears to be falling but it is still too soon to know whether the rubella vaccination programme in Western Australia has made a significant impact. The cohorts of young women who would have received the schoolgirl vaccination programme are only now entering the child bearing age groups. Observed falls may be due also to delayed diagnosis particularly of cases of deafness only. The proportion of nonimmune young women who would have been eligible for the programme in one maternity hospital has fallen. This study needs to be repeated to ascertain whether further epidemics of rubella have resulted in peaks of CRS or whether the vaccination programme has started to have an effect. PMID- 4041178 TI - A twin study of psychomotor and physiological responses to an acute dose of alcohol. PMID- 4041179 TI - No decline in assortative mating for educational level. PMID- 4041180 TI - Separated fraternal twins: resemblance for cognitive abilities. PMID- 4041181 TI - Effects of cobalt deficiency on the ovarian function in the East African short horned goat. AB - 24 normocyclic East African short-horned goats were made vitamin B12-deficient through feeding cobalt-deficient Rhodes grass (Chloris gayana) hay. The deficiency was confirmed by controls of the blood level, by the occurrence of anaemia, by increased cortisol levels, and by hypertrophy of the fasciculata and reticulata zones in the adrenal cortex. The oestrogen level increased initially, and then decreased markedly from the 3rd cycle on, and reached levels below those of the control. Ovulations finally ceased. It is suggested that ovarian dysfunctions during vitamin B12 deficiency are caused by changes in the endocrine profile. PMID- 4041182 TI - Kinetic studies on the interaction of streptokinase and other plasminogen activators with plasminogen and fibrin. AB - The activation of Lys-plasminogen to plasmin by streptokinase was promoted by soluble fibrin such that Km was decreased and Vmax. increased. Enhancement was also observed when Glu-plasminogen was the substrate and was shared by the preformed streptokinase-plasminogen activator complex, indicating that the stimulation was not exerted primarily on the rate of active site formation. PMID- 4041183 TI - Inhibition of phosphorylase kinase, and tyrosine protein kinase activities by quercetin. AB - Quercetin, a naturally occurring bioflavonoid inhibited the activities of phosphorylase kinase and a partially purified tyrosine protein kinase from rat lung. The inhibition was rapid and concentration dependent. Quercetin at 100 microM inhibited the activities of phosphorylase kinase and tyrosine protein kinase by about 95 and 80-90 percent respectively. ATP reversed the quercetin mediated inhibition of tyrosine protein kinase but not of phosphorylase kinase. These data suggest that quercetin has differential effect on different protein kinase activities and it may be used as a tool to probe the role of various protein kinases in cell function. PMID- 4041184 TI - The nuclear-bound form of the progesterone receptor is generated through a hormone-dependent phosphorylation. AB - The solubilized ("cytosolic") receptor present in the rabbit uterus in the absence of hormone and the chromatin-bound ("nuclear") receptor obtained after injection of a progestin were compared. Crude cellular extracts were analyzed by immunoblotting and receptors were purified by immunoaffinity chromatography. With both methods it was observed that the electrophoretic mobility of the "nuclear" receptor was slower than that of the "cytosolic" receptor. This difference in mobility appeared to be due to the existence of variably phosphorylated forms of receptor. The phosphorylation reaction was examined in uterine slices. In the absence of hormone the cytosolic receptor was phosphorylated. When hormone was added the phosphorylation of receptor was markedly enhanced and the electrophoretic mobility of the "nuclear" receptor was decreased. These experiments thus show that the receptor in its "cytosolic" form is a phosphoprotein. Under the effect of the hormone the receptor is further phosphorylated on some supplementary site(s). This polyphosphoprotein is the chromatin-bound, putatively active, form of the receptor. In this respect the intracellular progesterone receptor is similar to various membrane receptors for hormones and growth factors which are phosphorylated upon binding of their ligand. PMID- 4041185 TI - Failure of cis-platinum to alter metal concentrations in the liver and kidney of the rat. AB - The anticancer drug, cis-diamminedichloroplatinum, was administered to male rats at a dose of 0.5, 1.0, 2.0 or 4.0 mg platinum/kg body weight. After 48 hrs, the animals were killed and platinum, zinc, copper and metallothionein were measured in renal and hepatic tissue and platinum, zinc and copper were measured in the plasma. Administration of this platinum-containing compound did not induce hepatic or renal metallothionein and did not significantly alter the concentrations of copper or zinc in hepatic or renal tissue or in the plasma. PMID- 4041186 TI - [Renal puncture biopsy in the aged subject: apropos of 119 cases]. AB - We reviewed 119 renal biopsies performed between 1964 and 1982 on adults aged 60 or more. The two main indications wer: renal failure (35/119) and nephrotic syndrome (35/119). Histology showed: primary glomerular diseases (76/119), systemic diseases with renal involvement (31/119), arteriosclerosis only (5/19), tubulo-interstitial nephritis only (5/119). No obvious lesion was seen in 2 cases. Additional arteriosclerosis was observed in 21 cases and additional tubulo interstitial nephritis in 6 cases. Primary glomerular diseases consisted mainly in diffuse membranous glomerulonephritis (18/76). Systemic Lupus Erythematosus (7/31) and amyloidosis (6/31) represented most of the systemic diseases with renal involvement. The usefulness of renal biopsy in diagnosis, treatment and prognosis of a wide variety of renal diseases in elderly adults is demonstrated. PMID- 4041187 TI - [Benign sub-periosteal osteoblastoma of the nasal cavity. histological and ultrastructural study of a case]. AB - A case of periosteal benign osteoblastoma arising in the left nasal cavity is presented. The tumor develops on the surface of the middle turbinate without evidence of bone destruction. It has been locally excised and has not recurred in 3 1/2 years. The histological aspect is identical to that of the other cases of genuine osteoblastoma. The ultrastructure (the first of a periosteal osteoblastoma) is described. The osteoblasts resemble normal osteoblasts with a few exceptions: irregular nuclei, abundance of well-developed rough-surfaced endoplasmic reticulum and numerous fine filaments. The osteocytes and osteoclasts basically resemble their normal counterparts. The final diagnosis of benign osteoblastoma rests at the light microscopy level. The differential diagnosis are reviewed. Distinguishing histologic and ultrastructural characteristics between this tumor and other benign osteoblastic tumors are discussed. PMID- 4041188 TI - Theophylline overdose: acute single ingestion versus chronic repeated overmedication. AB - Currently available guidelines for managing theophylline intoxication do not distinguish between acute single ingestion and chronic repeated overmedication and do not reliably predict which patients should undergo hemoperfusion. Although hemoperfusion is widely recommended when serum concentrations exceed 40-60 mg/l, many patients with acute overdose tolerate much higher levels without serious toxicity. Because manifestations of toxicity might be dependent on the chronicity of the overdose, the authors retrospectively compared the clinical features of 15 patients with chronic repeated overmedication with those of 27 patients suffering acute single overdose. Patients suffering chronic repeated overmedication developed seizures (7/15) and serious arrhythmias (4/15) with serum levels of 28 70 mg/l. By contrast, only one of 19 patients suffering acute single overdose with peak levels less than 100 mg/l had seizures, and only two of 19 with levels less than 100 mg/l had serious arrhythmias. However, of the eight single-overdose patients with levels over 100 mg/l, seven had seizures and three had serious arrhythmias. Single-overdose patients were easily recognized by the presence of hypotension, hypokalemia, and low serum bicarbonate, features not present in chronic-type patients. Thus, while patients with theophylline overdose caused by chronic repeated overmedication frequently develop seizures and arrhythmias with serum levels of 40-70 mg/l, those with acute single ingestion are highly unlikely to suffer serious complications unless serum levels exceed 100 mg/l. Management of the intoxication, especially selection of patients for hemoperfusion, should be based on whether the overdose is caused by an acute single ingestion or chronic repeated overmedication. PMID- 4041189 TI - Recognition of psychological and cognitive impairments in the emergency department. AB - Ninety-six patients presenting to a university hospital emergency department were screened before triage for psychological symptoms or cognitive impairment using the General Health Questionnaire (GHQ) and Mini-Mental State examination (MMS). Charts were reviewed for demographic information and emergency physicians' recognition of psychological symptoms or cognitive dysfunction. Of the patients studied, 38% had positive results on the GHQ, and 18% had positive results on the MMS. Psychological symptoms or cognitive impairments were recognized by the emergency physicians in only 8% of those with positive GHQ results and 6% of those with positive MMS results. The usefulness of screening measures for psychological symptoms and cognitive impairment of emergency department patients is discussed. PMID- 4041190 TI - Pediatric catheter flow rates. AB - The flow rates of the 18- to 24-gauge catheters most commonly used in pediatrics were studied to determine which catheters and infusion techniques allowed for rapid volume replacement in infants and children. As expected, short, large diameter catheters were found to have a higher flow rate, and flows under pressure in the largest catheters tested were up to 17 times greater than in a longer, smaller diameter catheter. Catheters designed for peripheral venous insertion in children showed an 18 to 164% increase in flow rate when compared with the same gauge catheters designed for central venous use. Thus, intravenous access via a central vein does not guarantee more rapid fluid infusion unless the use of the central vein permits the insertion of a catheter larger in diameter than any that could be placed peripherally. Knowledge of the flow rates determined for the various catheters in this study will assist the physician in optimizing fluid resuscitation of the critically ill or injured child. PMID- 4041191 TI - Hypokalemia, hyperglycemia, and acidosis after intentional theophylline overdose. AB - Three cases of intentional theophylline overdose in adult patients are described. Among these, hypokalemia, hyperglycemia, and acidosis were found, and markedly elevated initial serum theophylline concentrations (106, 76.2, and 41.4 micrograms/ml) were measured. All patients recovered completely with conservative management. The observed biochemical abnormalities rapidly resolved during maintenance fluid therapy and modest potassium supplementation. In addition, seizures, ventricular arrhythmias, and other serious toxic effects were notably absent. PMID- 4041192 TI - Oven-cleaner pads: new risk for corrosive injury. AB - Over a six-month period, the New Jersey Poison Information System received 61 calls related to exposures to alkaline corrosives. Seven of these calls related to a new oven-cleaner product, oven-cleaner pads. These pads are sealed in a protective plastic wrap and contain lye in excess of 5%. Use of these products requires careful opening of the seal and caution in application. Five of the callers sustained injuries from their exposure, and three of these sustained burns, one in the oral cavity and one in the eye. None suffered permanent sequelae, but the potential for such is considerable. The method of application, concentration of base, and prolonged exposure to a widely covered area may make this product particularly hazardous. PMID- 4041193 TI - Tularemia: emergency department presentation of an infrequently recognized disease. AB - Tularemia is an uncommon, highly communicable disease occurring with seasonal regularity in endemic parts of the United States. The varied signs and symptoms may confound the unwary physician. Two cases are reported illustrating the ulceroglandular and ingestion forms of the disease. Septic (typhoidal), oculoglandular, pleuropulmonary, glandular, and oropharyngeal forms also are described. Knowledge of the epidemiology and a high index of suspicion should lead the examining physician to ask revealing questions. The diagnosis is presumed upon clinical grounds and confirmed by serological testing. According to published reports delayed diagnosis can result in an overall mortality rate of 7% of cases; however, early diagnosis will lead to uncomplicated recovery in most cases. PMID- 4041194 TI - Psychiatric screening in the emergency department: validation of the General Health Questionnaire. AB - Both a 28-item psychiatric scale, the Goldberg General Health Questionnaire (GHQ), and the National Institute of Mental Health (NIMH) Diagnostic Interview Schedule (DIS) were administered to 25 emergency department patients to determine the validity of the GHQ as a screening instrument for psychopathology in the emergency department setting. There was a significant association (P = 0.0343) between GHQ scores and DIS assessment. The sensitivity of the GHQ in this series was 55.6% and the specificity was 87.5% when compared with the DIS. This suggests that the GHQ may prove to be a valuable screening tool for patients with somatic complaints to detect unsuspected psychiatric illness in the emergency department. PMID- 4041195 TI - 1984 annual report of the American Association of Poison Control Centers National Data Collection System. PMID- 4041196 TI - Seizures in psychiatric patients. PMID- 4041197 TI - Fallacious arguments against resuscitation research. PMID- 4041198 TI - Methods of randomization in controlled clinical trials. AB - In this second article of a series that explores design and analysis issues in controlled clinical trials in emergency medicine, we have discussed the case for randomization, reviewed the methods involved in simple randomization, highlighted some of the practical problems involved with randomization, and presented some modified randomization schemes intended to remedy these problems. PMID- 4041199 TI - Theophylline poisoning. PMID- 4041200 TI - Use of psychiatric screening instruments in the ED. PMID- 4041201 TI - Retention of CPR skills. PMID- 4041202 TI - Calcium blockers in neurological recovery after cardiac arrest. PMID- 4041203 TI - Salicylate-induced pulmonary edema. PMID- 4041204 TI - Airway management in resuscitation. PMID- 4041205 TI - High i.v. infusion flow rates. PMID- 4041206 TI - [Breast-feeding during the process of transculturation]. PMID- 4041207 TI - [Secondary sex characteristics among Mexican boys 9 to 16 years of age. Horizontal study]. PMID- 4041208 TI - [Biological features of solutions available for oral hydration in Mexico]. PMID- 4041209 TI - [Fanconi's anemia]. PMID- 4041210 TI - [An urticaria, vasculitis and hypocomplementemia syndrome. Presentation of a case]. PMID- 4041211 TI - [Drowning in children]. PMID- 4041212 TI - Electrophysiological characteristics of amygdaloid central nucleus neurons during Pavlovian fear conditioning in the rabbit. AB - Recent evidence suggests that the amygdaloid central nucleus (ACE) may contribute importantly to cardiovascular adjustments in response to the presentation of conditioned emotional stimuli, possibly via direct ACE projections to cardiovascular regulatory nuclei in the medulla. The present experiment was conducted to obtain additional data relevant to this suggestion. Extracellular single-unit recordings were obtained from 85 histologically-verified ACE neurons during Pavlovian differentially conditioned heart-rate responding in rabbits. Conditioning involved pairing one tone (CS+), but not a second tone (CS-), with paraorbital shock. Those ACE neurons which project to the lower brainstem were identified by their antidromic responses to stimulation of a mesencephalic region through which descending ACE projections course. Under these conditions it was possible to classify ACE neurons as conforming to one of 6 general categories based on their spontaneous activity and conditioned response characteristics. In addition, it was determined that: (1) the electrophysiological characteristics of many ACE neurons were differentially altered in response to presentations of the CS+ versus the CS-; (2) the responses of many ACE neurons to presentations of the CS+ were correlated with the magnitudes of concomitant conditioned alterations in heart rate; and (3) the activity of antidromically-identified ACE neurons which project to the lower brainstem was decreased in response to presentations of each CS. These data provide additional support for the notion that the ACE contributes to cardiovascular regulation during the presentation of emotionally-arousing stimuli. PMID- 4041213 TI - The hippocampus and thalamus: their roles in short- and long-term memory and the effects of interference. AB - Rats with dorsal hippocampal, dorsomedial thalamic, and operated control lesions were administered a delayed alternation (DA) task in which recall was assessed over intervals ranging between 0 and 80 s, and a passive avoidance (PA) task, involving training-test delays of between 1 h and 21 days. On both tasks, hippocampal groups performed normally at relatively short intervals, but showed significant memory loss at longer intervals. Thalamic groups were generally impaired on the DA task, but performed as well as operated control groups at all intervals in the PA task. The data also indicated an exaggerated susceptibility to interference in the hippocampal groups and a loss of episodic and reference memory following hippocampal or thalamic lesions. Similarities between the performance of rats with hippocampal or thalamic lesions and comparably brain damaged human amnesics were noted. In line with current hypotheses, it was concluded that memory loss following thalamic damage is related to a deficit in the early stages of new learning, whereas hippocampal amnesia results from impairment at a later, integrative stage in which long-term memories are formed and durably stored. PMID- 4041214 TI - Visual analysis of body movements by neurones in the temporal cortex of the macaque monkey: a preliminary report. AB - Movement provides biologically important information about the nature (and intent) of animate objects. We have studied cells in the superior temporal sulcus of the macaque monkey which seem to process such visual information. We found that the majority of cells in this brain region were selective for type of movement and for stimulus form, most cells responding only to particular movements of the body or some part of it. A variety of cell types emerged, including cells sensitive to: translation of bodies in view, movements into view (appearance) or out of view (disappearance) and the articulation and rotation of the body/head. Directional selectivity for cells sensitive to translation tended to lie along one of 3 orthogonal Cartesian axes centred on the monkey (towards/away, left/right and up/down). One type of rotation sensitive cell was tuned to rotation about one or more of these axes, a second type was sensitive to different head rotations which brought the face to confront the monkey or turned the face away. Reconstructions of cell positions indicated that cells of the same type were clumped anatomically both across the surface of the cortex and perpendicular to the surface. PMID- 4041215 TI - Cerebellar lesion effects on vocalization of the squirrel monkey. AB - High-frequency coagulations were made in the cerebellar nuclei of 3 adult squirrel monkeys to test their role in the production of vocalization. Complete bilateral destruction of all 3 nuclei in one animal or destruction of their rostral or caudal halves in the other two had no effect on the acoustic structure of electrically elicited species-specific calls. PMID- 4041216 TI - Respiration and olfactory bulb unit activity in the unrestrained rat: statements and reappraisals. AB - The activity of 26 olfactory bulb units, including 19 mitral, 5 granular and 2 external plexiform cells, was recorded in unrestrained rats associating food odor stimuli/isoamyl acetate to a food reward/no reward. The respiratory activity was transduced from the intranasal air pressure and used as a time-base to analyze the unit discharge. The patterning of neuron activity was presented in histograms built from sequences of 30 successive cycles each resolved into 5 equal bins. 64 sequences were defined by the low or high respiratory frequency and by olfactory stimulation. In resting conditions, 15 (13 mitral) units displayed significant respiratory patterning, mainly characterized by the absolute and relative phases of the maximal and minimal activity in the cycle. Six typical groups of units could be defined accordingly. Increased respiratory frequency erased patterning, except in the 2 most typical units. The histograms from adjacent mitral cells showed that the various types were distributed as in a neuronal network with lateral recurrent inhibition, where noise was introduced at each inspiration. The data verified that the spatial and temporal distribution of the input activity elicited by the olfactory stimuli created local interferences, modifying the patterning of mitral activity. The odor-induced changes (R1 responses) were as consistent as the typology itself; they were selective and habituated rapidly. The transient R1 activity could also give rise to an R2 firing, atypical, regular and lasting, mainly when food odor elicited food intake. Possible functional interpretations of these phenomena are presented. PMID- 4041217 TI - Deficits in non-spatial conditional associative learning after periarcuate lesions in the monkey. AB - Monkeys with lesions of the periarcuate region of the frontal cortex were severely impaired in learning a nonspatial conditional associative task. In this task, either one of two non-spatial responses (open the lit or the unlit box) was correct if emitted in the presence of the appropriate stimulus. In contrast, the periarcuate monkeys were able to learn, at a normal rate, the control tasks in which only one of the two responses was correct (e.g., go to the lit box), the animal's task being to emit this response when the cue to do so was given. These findings support the hypothesis that the periarcuate cortex is critically involved in conditional associative learning. PMID- 4041218 TI - No cross-tolerance between the stimulatory and depressant actions of benzodiazepines in mice. AB - Doses of the benzodiazepines chlordiazepoxide and diazepam were selected that elevate, or that depress, exploratory and locomotor behaviour in the holeboard in mice, and the development of tolerance to these effects was investigated. Tolerance did not develop to the stimulant effects of low doses of these compounds after 10 or 20 days pretreatment with either a low (stimulant) dose or a high (depressant) dose of each. When animals were pretreated with a high (depressant) dose of the benzodiazepines, tolerance developed to the depressant effects of a high test dose, and in fact, after 20 days a stimulatory effect on head-dipping had developed with this dose. In contrast, however, after pretreatment with a high (depressant) dose, there was no tolerance to the stimulatory effects of a low test dose of the benzodiazepines, even after 20 days. The ability of current theories is concluded that behavioural theories of tolerance, such as an instrumental conditioning model, may be the most appropriate to explain the present results. PMID- 4041219 TI - Behavioural and neurochemical effects of chronic intraventricular injections of nerve growth factor in adult rats with fimbria lesions. AB - Rats received bilateral lesions of the fimbria. These lesions impaired their ability to learn a radial maze. Rats given repeated intraventricular injections of nerve growth factor (NGF, 10 micrograms twice weekly during 4 weeks after the lesion) learned the maze problem more rapidly than rats with the same injury but treated with a control protein (cytochrome c). When retested after a period of 6 weeks without NGF treatment, the performance of NGF-treated and cytochrome c treated rats with fimbria lesions did not differ. Whereas our previous study showed an increase in choline acetyltransferase (ChAT) activity in the septum and the hippocampus 4 days after the last NGF injection, the present study found that after the retest period (i.e. 10 weeks after the last NGF injection) ChAT activity was increased in the septum but not in the hippocampus. The relationship between the NGF-induced changes in ChAT activity and behaviour is discussed. PMID- 4041220 TI - Earlier is not always better: behavioral dysfunction and abnormal cerebral morphogenesis following neonatal cortical lesions in the rat. AB - Rats with lesions of the medial frontal, ventral frontal or posterior parietal cortex in adulthood were compared behaviorally and neuroanatomically in adulthood with rats with similar removals at 7 days of age. The neonatal lesions altered cortical morphogenesis, especially in the ventral frontal and parietal groups, in which there was a marked thinning of remaining cortex distal to the lesion site. Behavior was assessed on an extensive battery of sensorimotor and maze-learning tests. Although there was sparing of function on some tests, the overall result was very little sparing on sensorimotor tests and only partial sparing on tests of maze learning in the frontal groups. The parietal neonates showed sparing on only one sensorimotor task and, in addition, showed unexpected deficits on sensorimotor and maze-learning tasks that were not observed in the adult operates. The results suggest that there may be more localization of function in the infant cortex than is generally believed and that early cortical damage may produce different behavioral effects than similar damage in adulthood. PMID- 4041221 TI - On the ability of rats to discriminate between microstimulations of the olfactory bulb in different locations. AB - An investigation was made into the ability of rats to discriminate between electrical stimulations applied to the mitral cell layer of the olfactory bulb in different locations. Water-deprived rats implanted with permanent electrodes were trained to use single- or multi-site microstimulations as discriminative stimuli for selecting a palatable solution without tasting it in a two-choice test. Spontaneous reactions of the animals to stimulation with sinusoidal currents higher than 3 microA per electrode resembled sensory arousal. All rats were found to discriminate between the effects of concurrent microstimulations applied to bulbar sites separated by 500 micron. Changing the current intensity in the range 4-20 microA had no detectable effect on the discrimination. Discrimination was still possible, with a few exceptions, when electrodes were separated by 250 micron and even when they were closely adjacent. Spatial resolution of discrimination seemed not to vary in different regions along the rostrocaudal axis of the bulb. The discrimination of patterns of simultaneous stimulation at several sites was also investigated. Different multi-site patterns were easily distinguished, even when their respective components were closely adjacent or when some components occupied the same area. The findings are discussed with reference to the concept of spatial coding of odours in the olfactory bulb. PMID- 4041223 TI - DRL responding under uncertain reinforcement in rats after medial frontal cortical lesions. AB - Rats were studied for their performance on DRL 10-s schedule with a 50% probability of reinforcement of a correct response with a food pellet. It was found that the performance of a group of 8 rats with medial frontal decortication by aspiration was deficient compared to a group of 7 sham-operated control rats. The deficit manifested in the form of an increase in very short interresponse times (IRTs). This signifies an influence of medial frontal cortex on the control of responding by time-correlated stimuli probably arising from collateral behaviours. PMID- 4041222 TI - Differential effects of intrafrontocortical microinjections of dopamine agonists and antagonists on circling behavior of rats. AB - Asymmetric posturing and circling behavior resulting from acute unilateral manipulation of central dopamine have been used to assess this neurotransmitter's contribution to motor control. Although providing extensive evidence for the involvement of mesolimbic and nigrostriatal dopamine in motor activity, this approach has not been used to study the mesocortical system. We now report circling behaviour following acute manipulation of frontal cortical dopamine. Unilateral microinjections of the agonists, (+)-amphetamine (12 and 25 micrograms in 1.0 microliter) and LY 141865 (12 micrograms in 1.0 microliter) resulted in contraversive circling. Conversely, unilateral intrafrontocortical microinjections of the antagonist, metoclopramide (25 and 100 micrograms in 1.0 microliter) resulted in ipsiversive circling in amphetamine (1.5 mg/kg, i.p.) pretreated rats. Lower central doses of each drug and vehicle injections had no significant effect. These results provide evidence for an excitatory influence of mesocortical dopamine on motor control. This finding may implicate frontal cortical dopamine in the extrapyramidal motoric side effects of chronic neuroleptic treatment which previously have been attributed to dopamine function in subcortical areas. PMID- 4041224 TI - Red nucleus lesions impair acquisition of the classically conditioned nictitating membrane response but not eye-to-eye savings or unconditioned response amplitude. AB - Following a single electrocoagulating RF lesion aimed at left red nucleus, rabbits received classical conditioning of the nictitating membrane (NM) response. A tone was the conditioned stimulus (CS) and electrostimulation of the eye was the unconditioned stimulus (US). The US was applied to the right eye during the initial phase of training. It was then switched to the left eye to assess transfer of learning and ultimately switched back to the right eye. NM responses were recorded simultaneously from both eyes during each phase of training. Consistent with reports implicating a cerebellar-rubro circuit in this behavior, RN lesions disrupted acquisition of CRs in the eye contralateral to the lesion. Animals with disrupted NM CRs of the right eye resembled controls in showing transfer of conditioning to the left eye. CR-disrupting lesions did not affect UR amplitude. PMID- 4041225 TI - Spatial learning and memory, maze running strategies and cholinergic mechanisms in two inbred strains of mice. AB - The acquisition process of the radial maze task was studied in two inbred strains of mice, C57BL/6 and DBA/2. A quantitative and qualitative evaluation of performance was performed and the pretest level of activity was measured. The results showed a significant correlation between activity and performance since the highly active C57BL/6 mice exhibited better performance of the radial maze task than the less active DBA/2 mice. Moreover, for correct trials, strain dependent maze-running strategies were observed: while both strains displayed about the same percentage of clockwise and spatial strategies, it was observed that among the spatial strategies C57BL/6 used a larger number of different correct solutions. Subsequently, the effect of scopolamine administration on working memory processes was assessed in sequential and discrete trials. A different reactivity of each strain to anti-cholinergic treatment was found in discrete trials since only DBA/2 mice were impaired. The effect of scopolamine is discussed in relation to the different models of information processing involved in learning and memorizing the experimental rule. PMID- 4041226 TI - Influence of stress on morphine-induced hyperthermia: relevance to drug conditioning and tolerance development. AB - Controversy exists regarding (a) whether rats become tolerant, or sensitized, to morphine-induced hyperthermia and (b) the directionality of the conditioned pyretic effects of morphine. In these studies, stress produced by temperature assessment procedures affected rats' pyretic response to morphine. Under conditions of high stress, rats first showed diminished, and then enhanced, hyperthermic responding across repeated morphine dosing (5 or 35 mg/kg). The diminished hyperthermia can be attributed to habituation to high levels of assessment stress. Repeated morphine doses delivered under conditions of low stress produced only enhanced hyperthermic responding, which indicates that rats become sensitized to morphine's hyperthermic effects. There was little evidence that morphine supported conditioning of pyretic responses. Finally, the temperature-assessment stress that produced hyperthermia was mediated by opiate peptides, was blocked by naloxone, and enhanced the agonist effects of morphine. The relevance of these findings to theories of drug conditioning and tolerance is discussed. PMID- 4041227 TI - Effects of paced coital stimulation on estrus duration in intact cycling rats and ovariectomized and ovariectomized-adrenalectomized hormone-primed rats. AB - Feminine sexual behavior was examined in intact cycling rats and ovariectomized and ovariectomized-adrenalectomized hormone-primed rats with the use of a partitioned test cage in which the female controlled the timing of sexual contacts with males. Females received 9 or 10 intromissions in the partitioned test cage (paced) or with the partition removed (nonpaced) or received solitary exposure to the test cage or to mounts without intromission with the use of vaginal masks. Intact cycling (Experiment 1) and gonadectomized hormone-primed (Experiment 2) rats displayed similar patterns of contact with males: Exists from and latencies to return to the male compartment increased as the intensity of the antecedent coital stimulation increased (ejaculations greater than intromissions greater than mounts). Cycling females given experience with paced or nonpaced mating on the evening of proestrus did not exhibit differences in pacing behavior on a second test 17-24 days later. Those receiving paced coital stimulation showed a shorter duration of estrus than did those receiving nonpaced stimulation. Ovariectomized and ovariectomized-adrenalectomized paced rats given three successive doses of estradiol benzoate in combination with progesterone did not show shorter periods of estrus than nonpaced or mounts-only rats. These results suggest that ovarian output in response to paced cervical-vaginal stimulation may contribute to the termination of estrus in the rat. PMID- 4041228 TI - Ingestive responses to homeostatic challenges in rats with ablations of the anterolateral neocortex. AB - Because rats with either anterolateral neocortical or lateral hypothalamic (LH) damage initially display similar feeding and drinking deficits and recovery patterns, the possibility that anterolateral neocortical ablations would also produce similar chronic ingestive impairments to glucoprivic and hydrational challenges was examined. In general, rats with anterolateral neocortical ablations exhibited normal feeding responses to food deprivation and glucoprivation induced by insulin or moderate doses of 2-deoxy-D-glucose (2-DG), but their response to a high dose (500 mg/kg) of 2-DG was impaired. These animals also drank normally in response to hypertonic saline injections and following water deprivation, but only if food was available during the test session, results indicating that they drank prandially. Results indicate that although the anterolateral neocortex and LH are anatomically related, these brain regions appear to be functionally dissimilar in terms of the regulation of ingestion. PMID- 4041229 TI - Amphetamine tolerance and body weight set point: a dose-response analysis. AB - The theory that amphetamine anorexia and tolerance reflect the lowering of a set point for body weight regulation was evaluated. In the first experiment, rats given either 2 or 4 mg/kg d-amphetamine and access to milk ultimately achieved comparable levels of tolerance and maintained their weight at 94%-96% of control levels. Thus, the level of maintained body weight was not dose-dependent. In the second experiment, increasing the doses resulted in renewed anorexia and weight loss, and the appearance of behavioral stereotypies. Whereas mean intake then recovered, body weight remained at 79%-82% of control levels. However, milk intake for individual rats was extremely variable. Such variability is inconsistent with the notion that body weight was actively regulated by caloric intake. Drug withdrawal had little further effect on intake, and it led to weight "rebound" in only one group. When subsequently retested with the original doses, both groups were again anorexic and showed more intense stereotypy. This finding suggests that drug withdrawal caused a general increase in sensitivity to amphetamine, rather than a set-point-related change in feeding. Taken together, the data do not support the set point theory of amphetamine tolerance. PMID- 4041230 TI - Medial temporal lesions in monkeys impair memory on a variety of tasks sensitive to human amnesia. AB - Monkeys with conjoint bilateral lesions of the hippocampus and amygdala were impaired on four different tests of memory (delayed retention of object discriminations, concurrent discrimination, delayed response, and delayed nonmatching to sample). Because tests involving delays and distractions are known to be especially sensitive to human amnesia, in three of the tasks relatively long delay intervals between training and test trials were used, and in two tasks distraction was introduced during the delay intervals. The severity of the impairment increased with the length of the delay, and distraction markedly increased the memory impairment. For one task given on two occasions (delayed nonmatching to sample), the severity of the impairment was unchanged over a period of 1.5 years. Taken together with previous findings that skill learning is unimpaired in the same operated monkeys, the results of the present study strengthen the conclusion that monkeys with medial temporal lesions constitute an animal model of human amnesia. In addition, the four tasks used here appear to constitute a sensitive and appropriate battery that could be used in other studies of the neuroanatomy of memory functions in the monkey. PMID- 4041231 TI - Memory of monkeys (Macaca mulatta) with lesions in prefrontal cortex. AB - It is controversial whether damage to prefrontal cortex causes an impairment of memory. In this experiment, the tissue in sulcus principalis was removed in rhesus monkeys, and they were given 25 spatial locations to remember. They were poor at the task from the first. The same animals were able to indicate which of two locations they had touched if there was no delay before they were allowed to make their report. One possibility is that frontal mechanisms operate on information in working memory. PMID- 4041232 TI - Hippocampectomy disrupts the topography of conditioned nictitating membrane responses during reversal learning. AB - The effects of bilateral hippocampectomy on the topography, or shape, of conditioned nictitating membrane (NM) responses were examined during four learning tasks: one-tone delay conditioning, unpaired extinction, two-tone discrimination, and reversal of two-tone discrimination. Results showed that hippocampal ablation altered conditioned NM response topography only during reversal learning and not during the other training paradigms. In addition, the shapes of learning curves for hippocampectomized animals were different from those of control animals during reversal conditioning but not during the other paradigms. The implications of these findings with respect to unit-recording studies of hippocampal cellular activity during classical conditioning of the NM response are discussed. PMID- 4041233 TI - Sparing of patterned alternation but not partial reinforcement effect after infant and adult hippocampal lesions in the rat. AB - The effect of hippocampal lesions was assessed in patterned (single) alternation (PA) and the partial reinforcement extinction effect (PREE), the two reward schedule effects that appear earliest in ontogeny. Three groups of rat pups, with appropriate controls, were tested for each effect: lesion as infant/test as infant, lesion as infant/test as adult, and lesion as adult/test as adult. Hippocampal lesions had no effect on PA in any of the three conditions except for a suggestion that the effect was mildly attenuated in the animals given lesions as infants and tested as adults: The pups were able to discriminate rewarded from nonrewarded trials and to inhibit responding on nonrewarded trials. On the other hand, the PREE was eliminated under all conditions of testing, in each case because of an increase in persistence following continuously reinforced acquisition. The results are discussed in terms of the functional maturation of the hippocampus and a possible dissociation of mechanisms that mediate response suppression in PA and in the PREE in infant rats. PMID- 4041234 TI - Proactive behavioral effects of theta-driving septal stimulation on conditioned suppression and punishment in the rat. AB - In two experiments, a treatment phase of septal stimulation preceded the acquisition of free operant lever pressing on a random-interval 64-s reinforcement schedule. Male Sprague-Dawley rats, chronically implanted with a bilateral septal stimulating electrode and a unilateral bipolar hippocampal recording electrode, received (a) low-frequency (7.7-Hz) stimulation, which drove the hippocampal theta rhythm, or (b) random-pulse stimulation (average frequency = 7.7 Hz), which produced only nonregular waveforms in the hippocampus. Control animals were implanted but not stimulated. After 12 days of lever-press acquisition, animals were presented while lever pressing with an auditory signal associated with a particular schedule of shock delivery: In Experiment 1, shocks occurred despite the subject's response strategy; in Experiment 2, shocks were delivered only if the rat pressed the lever. In both experiments, lever pressing was suppressed by the auditory stimulus. Theta-driving but not random-pulse septal stimulation proactively increased behavioral tolerance to the effects of electric shock. These results reinforce the idea that proactive behavioral effects of septal stimulation are a consequence of the production of the hippocampal theta rhythm. PMID- 4041235 TI - Intraseptal scopolamine has differential effects on Pavlovian eye blink and heart rate conditioning. AB - The effects of intraseptal scopolamine hydrobromide injections on Pavlovian (classical) conditioning were evaluated, with tones used as the conditioned stimulus (CS) and a periorbital electric shock train as the unconditioned stimulus (UCS). Eye blink (EB) and heart rate (HR) conditioned responses were concomitantly recorded. Although injections of scopolamine into the medial septum impaired the acquisition of the Pavlovian conditioned eyelid reflex, these injections enhanced the magnitude of accompanying Pavlovian conditioned HR decelerations. However, scopolamine applied to the lateral septal area had no effect on EB conditioning, relative to the vehicle, but, like medial injections, enhanced the magnitude of the accompanying HR decelerations. These results are compatible with those of previous investigations: Medial septal dysfunction impairs somatomotor conditioning but leaves autonomic conditioning intact, and septal dysfunction produces a parasympathetic bias of the cardiovascular system. PMID- 4041236 TI - Age-related disruption of trace but not delay classical conditioning of the rabbit's nictitating membrane response. AB - Young (6 months of age) and old (36-60 months) New Zealand albino rabbits underwent classical conditioning of the nictitating membrane response in either a delay conditioning (Experiment 1) or a trace conditioning (Experiment 2) paradigm. There was no difference between old and young animals in acquisition of the conditioned response in the delay paradigm, nor were there any age-related differences in generalization to the tone conditioned stimulus (CS) or in sensitivity to the tone CS or eye shock unconditioned stimulus. In the trace conditioning paradigm, however, old animals acquired the conditioned response significantly more slowly than young rabbits. Because the same stimulus parameters and the same response were used in both experiments, it is unlikely that age-related differences in trace conditioning were due to stimulus sensitivity, motivation, or fatigue. The results are discussed in terms of how brain changes that accompany aging could differentially affect these two types of classical conditioning. PMID- 4041237 TI - Amino-acid sequence of human and bovine brain myelin proteolipid protein (lipophilin) is completely conserved. AB - Proteolipid protein (PLP) was isolated from white matter of human brain by chloroform/methanol extraction and further purified by chromatography. Performic acid oxidation yielded a product homogeneous in NaDodSO4-polyacrylamide electrophoresis with a molecular mass of 30 kDa. The carboxymethylated PLP was chemically cleaved with cyanogen bromide into four fragments: CNBr I 22-24 kDa, CNBr II 5 kDa, CNBr III 1.4 kDa and CNBr IV 0.7 kDa. HBr/dimethylsulfoxide cleavage at tryptophan residues released four fragments: Trp I 14-16 kDa, Trp II 2.0 kDa, Trp III 5 kDa and Trp IV 7 kDa. Hydrophilic fragments were enriched in 50% formic acid (CNBr II, III, IV and Trp II and III), whereas hydrophobic peptides precipitated from this solvent were CNBr I, Trp I and IV. The fragments were separated by gel filtration with 90% formic acid as solvent and finally purified by gel permeation HPLC (Si 60 and Si 100) for automated liquid and solid phase Edman degradation. Large fragments were further cleaved with different proteinases (trypsin, V8-proteinase, endoproteinase Lys-C and thermolysin). We used an improved strategy in the sequencing of the human proteolipid protein compared with our approach to the structural elucidation of bovine brain PLP. The amino-acid sequence of human PLP contains 276 residues, the same as found in bovine proteolipid protein. The two sequences proved to be identical. The possible importance of the conservative structure of this integral membrane protein is discussed. PMID- 4041238 TI - Purification and some properties of two isofunctional juglone hydroxylases from Pseudomonas putida J1. AB - Juglone-induced cells of Pseudomonas putida J 1 were shown to contain two isofunctional juglone hydroxylases. Both enzymes were purified about 125-fold to homogeneity in polyacrylamide gel electrophoresis. The molecular masses of the native enzymes, as determined by Sephacryl S-200 gel filtration were 59 000 Da for enzyme 1 and 56 000 Da for enzyme 2. The molecular masses of the subunits were determined by dodecyl sulfate polyacrylamide gel electrophoresis as 25 000 Da (enzyme 1) and 23 500 Da (enzyme 2). Both enzymes hydroxylated juglone, naphthazarin, 1,4-naphthoquinone and 2-chloro-1,4-naphthoquinone, but they were completely inactive against naphtholes. The activity of both hydroxylases was not affected by chelating agents, thiol reagents, however, were found to be strong inhibitors. No external cofactors such as Fe2, NADH, NADPH, FAD, FMN were required for activity. Concomitant with the hydroxylation of juglone the consumption of oxygen in a molar ratio 2: 1 (juglone: oxygen) was observed but none of the enzymes incorporated 18O2 into the substrate juglone. By activity staining enzyme 1 was found to be present in induced and non-induced cells of P. putida J 1, enzyme 2, however, only in juglone-induced cells. PMID- 4041239 TI - Properties and biochemical characterization of NADH 5 alpha-reductase from rat liver microsomes. AB - NADH 5 alpha-reductase is present in microsomes of various rat organs: heart and skeletal muscle, liver, adrenal glands, kidney, testes and prostate. The enzyme from rat liver microsomes utilizes B-hydrogen from the coenzyme NADH for steroid reduction. After solubilization of the enzyme with the nonionic detergent lubrol, phosphatidylcholine is necessary to restore the activity. This reactivation of the enzyme activity is paralleled by a corresponding increase of Vmax for testosterone (17 beta-hydroxy-4-androsten-3-one). Km and Vmax for testosterone change, Km and Vmax for the coenzyme NADH remain constant with an alteration of phosphate concentration in the incubation medium. The NADH 5 alpha-reductase is inhibited by numerous substances: amytal, phenobarbital, mepacrin, thenoyltrifluoracetone, gallic acid propyl ester, dicoumarol, pentachlorophenol, NADP and antibodies against rat liver NADPH ferrihemoprotein reductase. Antibodies against rat liver cytochrome-b5 reductase cause an activation of NADH 5 alpha-reductase. PMID- 4041240 TI - Stability and self-assembly of the S-layer protein of the cell wall of Bacillus stearothermophilus. AB - The surface layer of the cell envelope of Bacillus stearothermophilus consists of a regular array of protein subunits. As shown by dodecyl sulfate polyacrylamide gel-electrophoresis and ultracentrifugation, the fully solubilized S-layer protein represents a homogeneous entity with a subunit molecular mass of 115 +/- 5 kDa. Solubilization of the protein may be accomplished at acid pH, or using high concentrations of urea or guanidine X HCl. It is accompanied by (partial) denaturation, thus interfering with the characterization of the protein in its unperturbed native state. Removal of the solubilizing agent by dialysis or dilution allows the S-layer to be reassembled into two-dimensional crystalline lattices identical to those observed in intact cells. To determine the kinetics of association, optimum conditions are found to be rapid mixing with 0.1 M sodium phosphate pH 7.0, 20 degrees C, final protein concentration greater than 10 micrograms/ml. If the time course of the self-assembly is monitored by light scattering, as well as by chemical cross-linking with glutardialdehyde, multiphasic kinetics with a rapid initial phase and slow consecutive processes of higher than second-order are observed. The rapid phase may be attributed to the formation of oligomeric precursors (Mr greater than 10(6) ). Concentration dependent light scattering measurements give evidence for a "critical concentration" of association, suggesting that patches of 12-16 protein subunits fuse and recrystallize into the final (native) S-layer structure. Recrystallization tends to be complete. PMID- 4041241 TI - Mole rat hemoglobin: primary structure and evolutionary aspects in a second karyotype of Spalax ehrenbergi, Rodentia, (2n = 52). AB - The hemoglobins of the four karyotypes of Spalax ehrenbergi (2n = 52, 54, 58, 60) did not show any differences in their electrophoretic pattern and in high performance liquid chromatography. The complete amino-acid sequence of mole rat hemoglobin (Spalax ehrenbergi), chromosome species 2n = 52, is presented. It was elucidated by automatic Edman degradation of the chains, the tryptic peptides, and the C-terminal peptide obtained by acid hydrolysis of the Asp-Pro bond in beta-chains. The alpha- and beta-chains are identical with those of the chromosome species 2n = 60. A comparison of the hemoglobins of mole rat, mouse, and other rodents shows homology but no indication of adaptation to subterranean life. In all probability alpha 11(A9)Arg and alpha 120(H3)Gly, unique in mole rat among all mammalian hemoglobins, are not involved in high oxygen affinity. The construction of a phylogenetic tree by the maximum parsimony method, based on hemoglobin sequences, made it possible to show that Rodentia originated as a monophyletic clade, and to find the phylogenetic relationship of Spalacidae to other Rodentia (Mus, Rattus, Ondatra, Mesocricetus, Citellus, and Cavia). Among all rodents the slowest rate of nucleotide replacements occurred in the lineage to Spalax (20%) and the fastest in the lineage to Cavia (59%). PMID- 4041242 TI - Insulin receptor protein rendered visible in triton X-114 membranes. AB - Insulin receptor protein has been visualized by electron microscopy. This was rendered possible after the molecules had been extensively purified and had been reinserted into Triton X-114 membranes in a situation similar to that found in biological membranes. Freeze fracturing then revealed the insulin receptor molecules as particles randomly distributed in the fracture plane of the artificial membranes. The sizes of the particles are in the range expected from biochemical data. PMID- 4041243 TI - [Comparative evaluation of the diagnostic specificity and sensitivity of third generation tests by the detection of hepatitis B virus markers in the serum. I. HBsAg]. AB - The authors have evaluated comparatively the diagnostic reliability of the most recent RIA and ELISA mono-polyclonal techniques for the determination of HBsAg in serum by means of in vivo and in vitro tests. Statistically, no difference has been found as regards the various methods. PMID- 4041244 TI - In vitro cellular immune response in mice and rabbits immunized with Trichinella spiralis antigen. AB - The possibility of using cell mediated immune response as a diagnostic tool has been investigated with T. spiralis laboratory/model. The feasibility of a in vitro microculture method to measure blast cell activity of lymphoblasts in mice experimentally infected with T. spiralis muscle larvae or immunized with soluble crude antigen and the lymphoproliferative response in immunized rabbits was demonstrated. The obtained results suggest that the cell mediated immune response from blood lymphocytes may be very useful to diagnose early parasite infections. PMID- 4041245 TI - [Description of a case of type E botulism in Italy]. AB - The authors report the first documented italian case of type E botulism. The initial symptoms were typical permitting prompt diagnosis; the symptoms became severe and the patient had to be moved to intensive care. Biological tests on guinea-pigs showed the presence of type E botulin toxin in the tuna (stored in oil) which the patient had eaten 24 hours prior to admission. This tuna had been caught near the mediterranean coast of Spain several months earlier and canned at home. The authors emphasize that, even though this fish was imported, there is a danger that this intoxication could, in the future, be more widely observed. PMID- 4041246 TI - [Treatment of vaginal candidiasis with a new imidazole derivative, oxiconazole]. PMID- 4041247 TI - [Characterization of plant extracts of pharmaceutical importance]. PMID- 4041248 TI - Microbiological assay methods of some cephalosporins. PMID- 4041249 TI - [HPLC method for the determination of plasma and tissue levels of denzimol hydrochloride]. PMID- 4041250 TI - [Ubidecarenone (coenzyme Q10) in the therapy of chronic cor pulmonale]. PMID- 4041251 TI - [Comparison of the relative bioavailability of coenzyme Q10 in two tablet preparations. The use of coenzyme Q10 in geriatric gynecologic surgery]. PMID- 4041252 TI - [Chromosome mapping by in situ hybridization of cloned human DNA sequences]. PMID- 4041253 TI - [Ultrastructural aspects of gonadotrophic cells of the rat after stimulation with acupuncture]. PMID- 4041254 TI - Fluorescent protein bodies in Cercis siliquastrum L. endosperm. PMID- 4041256 TI - [Radiometric analysis of digitalis receptors in intact human red cells]. PMID- 4041255 TI - [Plasma variations in prolactin half-way through treatment with H2-antagonists]. PMID- 4041257 TI - [Changes induced by sulfhydryl reagents in the membrane potential of rat liver mitochondria]. PMID- 4041258 TI - Short term stimulation of lipogenesis by triiodothyronine in rat hepatocyte cultures. PMID- 4041259 TI - [Reactivity to somatic stimuli of callosal single fibers in the awake cat]. PMID- 4041260 TI - [Analysis of conduction in somatosensory pathways in man]. PMID- 4041261 TI - A model of writing performance: evidence from a dysgraphic patient with an "allographic" writing disorder. PMID- 4041262 TI - A model of spelling production: evidence from phonological dysgraphia in Italian. PMID- 4041263 TI - A model of oral reading: evidence from an Italian acquired phonological dyslexic patient. PMID- 4041264 TI - Effect of dietary n-6 and n-3 fatty acids on brain fatty acid composition in sea bass (Dicentrarchus labrax L.). PMID- 4041265 TI - Dietary oils and oxidative phosphorylation in rat liver mitochondria. PMID- 4041266 TI - Chemical carcinogenesis. III. Ring-cleaved derivatives of 1,7-diethylguanosine in tRNA ethylated in vivo and in vitro with ethylnitrosourea. PMID- 4041267 TI - Functional properties of the unstable Hb-Torino: alpha 43 (CD-1) Phe-Val. PMID- 4041268 TI - Age and/or sex differences of blood glucose and urea in school children. PMID- 4041269 TI - Etiopathogenic theory of ileocecocolic intussusception. AB - Right hemicolectomy was done in a three and a half month old infant presenting irreductible acute intestinal intussusception. Analysis of the anatomical specimen allowed confirmation of the authors' histological theory on the genesis of infantile intussusception. Histological study demonstrated the key elements of this theory: thickness of the cecal musculosa clearly less than that of the right colon, thereby accounting for the lesser resistance of the former; contribution to the outer longitudinal muscle fibers of the ileum and colon to the constitution of the ileocecal valve commissures. These longitudinal muscle fibers did not span across the base of the ileocecal valve. PMID- 4041270 TI - Tubular colonic duplications. A case report and literature review. AB - Tubular colonic duplication is a rare abnormality. The authors report here on a patient with rather nonspecific symptoms, whose abnormality was only discovered at operation. The good results obtained by a simple operative treatment of such forms contrast with the difficulties arising in clinical and radiological diagnosis. The characteristics of tubular colonic duplication are pointed out, which set it apart from all other types of duplication. PMID- 4041271 TI - A gliding space between the femoral artery and inguinal ligament: mechanism of formation of false aneurysm. AB - False aneurysms preferentially arise in the inguinal region subsequent to aorto femoral bypass. This finding suggests that the position of the inguinal ligament against the anterior surface of the prosthesis may be an etiological factor. Description of the inguinal region, forming a borderline between the trunk and thigh and specific to the erect posture, has been the subject of many anatomical studies. These papers describe mainly the relations between the vascular sheath of the femoral artery, the fascia transversalis and inguinal ligament. Based on a series of anatomical dissections we have found a gliding space between the femoral artery and inguinal ligament. This finding has led us to propose section of the fibrous portion of the inguinal ligament and the insertion of free omentum between the arch of the ligament and prosthesis in order to prevent false aneurysm. Preliminary results obtained with this technique are satisfactory. PMID- 4041272 TI - Rotation and forward displacement of the right kidney in hepatomegaly. AB - In a dissecting room cadaver, with an enormously enlarged liver, the right kidney was found rotated and displaced forward and downward. The anterior (inferior) pole of this kidney appeared bulging under the inferior border of the liver, reaching the anterior abdominal wall. An explanation for the changes which occurred during the development of the hepatomegaly and resulted in the displacement of the kidney are analyzed. The practical clinical implications that such a variation may have, either diagnostic or surgical, are stressed. The findings in the left kidney or an aberrant inferior polar artery, arching around and compressing the renal vein, are also described and analyzed. PMID- 4041273 TI - A new ligament: the "gastro-pancreatic". AB - The authors wish to draw attention to the gastro-pancreatic ligament (gastropancreaticus), no description of which is to be found in the usual anatomy text-books or in literature. The presence of this anatomic element can suggest new interpretations of the embryological development of the pancreas. PMID- 4041275 TI - Clinical anatomy in France is twenty years late: a chance to be seized. PMID- 4041274 TI - Anatomy in Britain 1985. PMID- 4041276 TI - Anatomical study of digital compression of the vertebral artery at its origin and at the suboccipital triangle. AB - Manual compression of the vertebral artery is used in routine clinical practice for diagnosis of positional hemodynamic vertebro-basilar insufficiency (VBI). The supraclavicular and suboccipital areas were carefully dissected in 20 cadavers. Anatomical variations observed on dissection were compared to angiographic data from 150 patients and data from the literature. Objective results of manual compression of the vertebral artery can be obtained by sonography. In patients with VBI, such compression induces signs of reversible cerebellar or brain stem ischemia, whereas no signs are observed in patients without VBI. PMID- 4041277 TI - Lymphaticovenous communications. Role of the lymph nodes. AB - There is a physiological necessity for the existence of lymphaticovenous communications in points other than the terminal entry of the lymphatic trunks into the superior caval system. These communications are frequently seen, as well in clinical practice as in experimentation, when there is an obstacle to the downstream lymphatic flow, but their exact nature cannot be determined. We have been able to demonstrate on the rat that such communications are established within the lymph nodes. We shall discuss the physiological importance of our findings together with a review of the literature and consider their clinical and therapeutic consequences. PMID- 4041278 TI - Radiological anatomy of the bile ducts based on intraoperative investigation in 250 cases. AB - Intraoperative cholangiograms were studied in 250 patients. Analysis of the data obtained led to the establishment of a protocol for intraoperative cholangiography aimed at identification of anatomical anomalies and variations. Diagnosis of the latter must be achieved in order to avoid possible intraoperative complications. The common hepatic duct was formed by the junction of the right and left hepatic ducts in 52% of the cases studied. Absence of convergence of the posterior and anterior rami of the right hepatic duct was found in 30% of cases. Anatomical variations of the right sectorial duct system were seen in 12% of cases. Conversely, variations of the left sectorial duct system were rarely seen (2% of cases). Careful examination of the intraoperative cholangiograms led us to suspect certain anatomical variations in close to 1% of cases. These variations included abnormal hepatocystic duct, which if undiagnosed could lead to choleperitoneum or inadvertent ligation of the right hepatic duct. An abnormal hepatocystic duct terminating on the gall bladder was found in one patient. Study of the origin of the common bile duct allowed us to define the mode of termination of the cystic duct (on the right margin of the common hepatic duct in 80% of cases) and to identify a short choledochus in 2% of cases. Finally, variations of the duodenal termination of the common bile duct were studied and reflux into the pancreatic duct was seen in 27% of cases. However, the pathological significance of such reflux was rarely found. PMID- 4041279 TI - Experience based on 800,000 newborn screening tests of the Budapest Phenylketonuria Centre. AB - 800 000 newborns were screened for hyperphenylalaninaemia by the Guthrie-test in the Budapest PKU Centre in the 10 and a half years since 1 May, 1973. The blood samples were taken from mature newborns on the fifth and from premature babies on the fourteenth day of life. All infants exhibiting a level equal to or exceeding 12 mg/dl were telegraphically invited to the Centre and those having a level of 15 mg/dl or higher were put on an appropriate diet. The patients were classified according to the result of the phenylalanine tolerance 73 were found to have classical phenylketonuria and 15 had atypical phenylketonuria. The total incidence of phenylketonuria was thus 1: 9091. The mean age at introduction of diet was 30 +/- 15 days during the first period, while 21 +/- 11 days during the second period. Infants having an initial value of 4-12 mg/dl were kept under continuous control; among them 69 were found to have benign hyperphenylalaninaemia (HPA). The PKU/HPA ratio amounted to 1.28. Both screening and care were carried out by the Centre, and the practice of care is described in detail. A preliminary evaluation of the therapeutical results with a view of the patients' social class is offered. Phenylalanine levels during the diet were greatly influenced by the familial background and the sociocultural environment. PMID- 4041280 TI - Bronchial hyperreactivity after infantile obstructive bronchitis. AB - A follow-up study was performed on 406 patients treated for infantile obstructive bronchitis during the period between 1964 and 1973. Their mean age was 12.6 years at the time of the study. The male: female ratio was 1.7. Forty-three patients (11%) became asthmatic within 10 years after onset of the wheezy episode of infancy. In one-third of the 363 non-asthmatic children, bronchial hyperreactivity was shown by acetylcholine and histamine provocation. There was a significant correlation between the number of recurrent obstructive episodes and the length of the period of recurrent wheezing on the one hand and bronchial hyperreactivity on the other hand. PMID- 4041281 TI - Chromatographic screening of 70,328 neonates for inborn errors of amino acid metabolism. AB - Between the years 1974 and 1984, amino acid chromatography was performed from dried blood spots and partly from urine of 70 328 neonates. Six cases of phenylketonuria, one histidinaemia, one hyperglycinaemia and three cystinurias were found. Since all these could have been detected by other methods, the regional screening was discontinued in agreement with international recommendations. PMID- 4041282 TI - Coincidence of paternal 13pYq translocation and maternal increased 13p NOR activity in a child with arthrogryposis and other malformations. AB - Cytogenetic examination of a boy with congenital multiple arthrogryposis, VSD and dysmorphic facies revealed a probable t(Y; 13)(q?; p1) translocation and three NOR-positive dots on one of the chromosomes 13. The latter variant could be followed in the family of the mother, the 13/Y translocation was found in the relatives of the father. Since all the family members affected by one or the other cytogenetic anomaly were healthy, the abnormal phenotype of the propositus was interpreted as coincidence by chance. PMID- 4041283 TI - Ring chromosome 4: Wolf syndrome and unspecific developmental anomalies. AB - A new case of ring chromosome 4 in a 18-month-old girl is described. The patient presented extreme growth failure, psychomotor retardation, and some features of 4p deletion or Wolf syndrome. No significant loss of genetic material could be seen by G-banding technique (breakpoints p16q35). The ring was found to be unstable both in lymphocyte and fibroblast culture and a substantial proportion of aneuploid cells containing derivatives of the ring could be observed. An increased cell death-rate could be detected by cell viability determination with trypan blue in the first subculture of skin fibroblasts. It is suggested that this finding is a consequence of behavioural instability of the ring at mitosis existing probably in vivo as well. The clinical and cytogenetic findings in this patient were compared with those in the other 16 cases with ring 4 published so far. It is suggested that the phenotype in patients with this chromosomal anomaly is a mixture of phenotypic abnormalities generated by both the chromosomal deletion prior to ring formation (features of Wolf syndrome) and the behavioural instability of the ring at mitosis (unspecific developmental anomalies). PMID- 4041284 TI - Subacute sclerosing panencephalitis in twins. AB - Development of subacute sclerosing panencephalitis after measles has been observed in twins although the disease seems to be quite exceptional in members of the same family, and no report has been found on its occurrence in twins. PMID- 4041285 TI - [Long-term follow-up study of selective VIM-thalamotomy]. AB - To evaluate the effect of the physiologically defined selective Vim-thalamotomy on tremor type Parkinson's disease (PA, 26 cases) and essential tremor (ESS-T, 16 cases), a long-term follow-up study was conducted. The follow-up time extended from 4 months to 7 years (mean: 3.6 years). On 42 cases a total of 49 operations (4 bilateral surgery and 3 reoperations) were carried out. After identifying kinesthetic neuron, the coagulative lesion was made by using Leksell's apparatus between two needles of 4 mm effective tip length located with 3 mm interval including the recording point. One coagulation (unit lesion) destroyed about 20 mm3 brain tissue taking account of the mechanical damage by the needles themselves. The unit lesion was added around an imaginary cylinder of 3 mm radius, until the tremor was abolished completely. On the basis of number of unit lesion and its extent within an imaginary cylinder, these 49 operations were divided into the following group. Group I (minimal lesion group): coagulative lesion of 1 to 3 units within a quadrant of the imaginary cylinder. Group II: 3 to 5 units within 1/2 to one cylinder. The early (14 days after operation) and the late results on the tremor were evaluated clinically and electromyographically by 4 different categories: complete abolition, slight residual, residual, and recurrence in a strict sense. The late results in 13 PA cases of group I (similar to the early results) were: 10 complete abolition, 2 slight residual and one recurred, this case was reoperated 3 months after first operation and therefore categolized in group II. The late results in 11 ESS-T cases of group I were: 6 complete arrest, 4 slight residual, and one recurred case, which had been reoperated 2 years after operation. Therefore in a total of 24 minimal lesioned cases with PA and ESS-T complete abolition in 16, slight residual in 6, and 2 reoperated cases. In these successful 22 cases with minimal lesion, the tremor was abolished without noticeable long-lasting side effect. In other 20 cases with PA and ESS-T of group II, the tremor was almost completely relieved and maintained. In conclusion, by radiographically and physiologically controlled selective Vim thalamotomy for Parkinsonian and essential tremor, it was shown that the effect of minimal lesion was valid and well maintained on the long-term follow-up base. PMID- 4041286 TI - [Study of adult cases of moyamoya disease]. AB - Fifty-one adult patients with moyamoya disease were studied. Among these, thirteen cases, which had the history of cerebral ischemic attack during childhood, are classified as the cases of juvenile onset. The other thirty-eight cases were classified as those of adult onset. In most of the cases of juvenile onset, occlusive lesions also affected cortical arteries. For these cases, it is important to perform STA-MCA double anastomoses and encephalo-myo-synangiosis. Those of adult onset resembled the pathophysiology of internal carotid artery occlusion, or that of middle cerebral artery occlusion, since few cortical artery occlusion was noted, and leptomeningeal anastomosis was well developed. STA-MCA anastomosis was considered to be the treatment of choice in those of adult onset. PMID- 4041287 TI - [Effect of intravenous administration of diltiazem on cerebral blood flow and brain function]. AB - The effect of intravenous administration of diltiazem on cerebral circulation and brain function were studied in animals. Diltiazem, at a dose of 150 micrograms/kg BW, was administered intravenously over a period of 5 minutes beginning 30 minutes after ligation of the right brachiocephalic artery in 9 cats in order to investigate its effects in the acute stage of cerebral ischemia. In 5 animals, mean arterial blood pressure was recorded and blood flow in the basilar artery was measured transdurally by use of an ultrasonic Doppler flow-meter. Mean arterial blood pressure began to elevate immediately after ligation of the right brachiocephalic artery, but the degree of elevation was minimal. It began to fall during diltiazem injection and returned to the preadministration value 30 minutes after injection. Basilar artery flow decreased slightly during injection of diltiazem, but began to increase after completion of injection. The increase relative to the preadministration value was 62 +/- 31% 10 minutes after injection, 88 +/- 38% 20 minutes after, and 24 +/- 53% 30 minutes after. The short latency somatosensory evoked potentials (short latency SEP) recorded in the other 2 animals showed no noticeable change either in amplitude or latency during the same procedures. In 1 of 2 animals in which brainstem auditory evoked potentials (BAEP) were monitored, the latency of peak IV increased after ligation of the right brachiocephalic artery, and decreased 20 minutes after injection of diltiazem.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4041288 TI - [A sudden-death in a case of Arnold-Chiari malformation (type I) with sleep apnea]. AB - We presented a sudden-death case of Arnold-Chiari malformation (type 1) accompanied with spina bifida and closed meningomyelocele. Polysomnography revealed the increase of both central and mixed type apneas to compare with the findings of typical Pickwikian syndrome. THE CASE: 30-year-old female without obese or obstruction of upper air way. Spina bifida and closed meningomyelocele at sacral portion were found at her birth. She had no treatment and had not been able to walk because of paralysis at low extremities. Since she was 25-year-old, she had had insomnia which accompanied by choked feelings, palpitations, clumsiness of hands and anxiety. Snoring was light, and she had neither respiratory disturbances nor hypersomnia during awake. She was admitted to our hospital for treatment of decubitus. 2nd June, 1977, she was found acrocyanosis during sleep and immediately she was resurrected. Physical examinations revealed there was no accounting for sudden respiratory arrest: the cardio-pulmonary system was normal during awake and laboratory findings also failed to disclose the episode. But she had slight dysfunctions of lower cranial nerves: fine nystagmus according to the head-position, decreased gag reflex, and paresis in the recurrence nerve of N.XII and etc. Angiography showed communicating hydrocephalus. Though ventriculoperitoneal shunt operation was performed at 8th June, sleep apnea could not be improved. Therefore we examined in order to clarify her sleep apnea. She was not obese, we could not find any obstructions of upper air way. Nocturnal polygraphy was performed at 8th July. The results were summarized as follows: (1) Total sleep time was 293 minutes and numbers of sleep apnea were 134 times.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4041289 TI - [Nuclear magnetic resonance imaging in a case of facial myokymia with multiple sclerosis]. AB - A 59-year-old female of facial myokymia with multiple sclerosis was reported. In this case, facial myokymia appeared at the same time as the first attack of multiple sclerosis, in association with paroxysmal pain and desesthesia of the neck, painful tonic seizures of the right upper and lower extremities and cervical transverse myelopathy. The facial myokymia consisted of grossly visible, continuous, fine and worm-like movement, which often began in the area of the left orbicularis oculi and spread to the other facial muscles on one side. Electromyographic studies revealed grouping of motor units and continuous spontaneous rhythmic discharges in the left orbicularis oris suggesting facial myokymia, but there were no abnormalities on voluntary contraction. Sometimes doublet or multiplet patterns occurred while at other times the bursts were of single motor potential. The respective frequencies were 3-4/sec and 40-50/sec. There was no evidence of fibrillation. The facial myokymia disappeared after 4-8 weeks of administration of prednisolone and did not recur. In the remission stage after disappearance of the facial myokymia, nuclear magnetic resonance (NMR) imaging by the inversion recovery method demonstrated low intensity demyelinated plaque in the left lateral tegmentum of the inferior pons, which was responsible for the facial myokymia, but X-ray computed tomography revealed no pathological findings. The demyelinated plaque demonstrated by NMR imaging seemed to be located in the infranuclear area of the facial nerve nucleus and to involve the intramedurally root.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4041290 TI - [Cerebral venous thrombosis with familial antithrombin III deficiency]. AB - A case of cerebral venous thrombosis with familial antithrombin III (AT III) deficiency was reported and we discussed the anticoagulant therapy of cerebral venous thrombosis from the viewpoint of AT III. The patient, a 17-year-old boy, was admitted to our clinic with severe bifrontal headache, generalized convulsions and progressive disturbance of consciousness. He developed deep vein thrombosis in his right leg and pulmonary emboli two years earlier when he was placed on heparin and so forth, followed by warfarin sodium. Warfarin was terminated 9 months prior to his recent illness. On neurological examination on admission, he was semicomatous with blurred disc margins, roving eye movements with right abducens nerve palsy, nuchal stiffness and right flaccid hemiplegia. Left carotid angiogram and CT scan revealed extensive superior sagittal sinus thrombosis, complicated with hemorrhagic infarcts in bilateral frontal lobes. When examined for coagulation studies, the patient and his father had decrease in AT III activity and antigen levels. He was treated successfully with antiedematous agents and anticonvulsants during acute phase of illness. He was thereafter placed on warfarin 5-6 mg/day with no further clinical thromboembolic event for 2 years 9 months. There was no neurological abnormality when he was last examined, although he was treated with valproic acid 1,200 mg/day and phenytoin 250 mg/day to control occasional adversive seizures. A coagulation study following infusion of 5,000 units of AT III was carried out. Warfarin was discontinued the day before the study. 0.64 U/kg of AT III administration resulted in a 1% increase in AT III level after the infusion. The biological half life of AT III was 14.4 hours.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4041291 TI - [A case of male prolactinoma presenting extremely high serum prolactin levels and biphasic response to CB-154 suppression test]. AB - A 33-year-old male was admitted to the Department of Neurosurgery, Fukui Medical School with a complaint of headache. There were no neurological deficits on admission. Craniogram demonstrated a so-called "phantom sella". A computed tomography revealed a high density mass lesion and the mass was enhanced well, that mainly extended from the sella to the left middle cranial fossa. The left carotid angiogram revealed an avascular mass lesion extending from the sella to the left middle cranial fossa. Pituitary function tests revealed an extremely high serum prolactin (PRL) levels (70, 100 ng/ml). PRL response to TRH was delayed in peak and the high level continued. Serum PRL levels elevated to 90, 800 ng/ml at 180 min after injection of TRH. A biphasic response was demonstrated in response to CB-154 suppression test to PRL secretion, that is, CB-154 stimulated PRL release initially (up to 90 min) and suppressed thereafter. Serum PRL levels (178, 400 ng/ml) reached to peak about 90 min after CB-154 administration. Response of growth hormone (GH) and adrenocorticotropic hormone (ACTH) to insulin were also impaired. Craniotomy was performed. The tumor was partially removed and was diagnosed as a prolactinoma histologically. Tumor tissue removed was subjected to the monolayer culture and electron microscopic study. Their observations demonstrated hyperactive PRL secretion of the individual cells. A total dose of 5,000 rads was irradiated postoperatively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4041292 TI - [An autopsy case of hereditary ataxia (hereditary spastic ataxia)]. AB - An autopsy case of hereditary spastic ataxia is reported. There are four family members with similar symptomatology through three generations. A 36-year-old man developed atactic gait at the age of 22 years, with following dysarthria, scanning speech, pyramidal signs, dysmetria, dysdiadochokinesia, nystagmus and mild sensory disturbance. The clinical course was steadily progressive and terminated about 14 years after the onset. The gross examination showed smallness of the brain stem and spinal cord with marked symmetrical atrophy of the anterior and lateral columns, especially at thoracic level. Histologically, pronounced degeneration was found in the anterior and posterior spino-cerebellar tracts, spino-thalamic tracts, and spinal ganglia. The olivary nuclei, pons and cerebellum were spared. The dentate nuclei showed considerable loss of neurons with degeneration, however there were no clinical signs related to this pathology. This case is considered to fall in the group of hereditary spastic ataxia according to Greenfield's classification, however, there was no report on degeneration of the dentate nucleus in this disease for the present. Hereditary spastic ataxia is very rare disease and only four cases have well been documented in our country to the best of our knowledge. The presence of nystagmus and superficial sensory disturbance, and sparing of the posterior column of the spinal cord seems to be common clinico-pathology in Japanese cases, differing from those of foreign cases. The fact that reactive astrogliosis was immunohistochemistry demonstrated in the degenerative regions of the spinal cord and where is no discrepancy between degenerative and reparative processes as reported before is stressed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4041293 TI - [Intravascular treatment of carotid-cavernous sinus fistulas]. PMID- 4041294 TI - Digitalis: where are we now? PMID- 4041295 TI - Changing digoxin potency and cardiac mortality in England and Wales 1968-76. AB - Data on monthly totals of cardiac deaths in England and Wales were examined in different ways to see whether there were any unexplained fluctuations in rates both at the time of an unplanned increase in the bioavailability and therefore the potency of the Lanoxin brand of digoxin in May 1972 and also when there was a coordinated increase in the bioavailability of other brands in October 1975. Despite advice to prescribers, dosages were not proportionately reduced in the 600 000 patients who were on treatment. Monthly totals of deaths from cardiac causes were high through the summer of 1972 but not at the end of 1975 and the excess in 1972 seems to be related to a cold summer. There was no evidence of a consistent or specific effect of changes in digoxin potency, either beneficial or harmful, on deaths from all cardiac causes or in specific subgroups in which digoxin treatment was likely to be most common. Although major changes in digoxin potency in England and Wales did not seem to produce a repeatable effect on death rates, data from other countries should also be examined for evidence of such an effect. PMID- 4041296 TI - Rapid plasma digoxin assay in outpatients--a useful routine technique? AB - In 25 outpatients taking digoxin for chronic atrial fibrillation (established for at least six months) a prospective study identified only one case in which rapid availability of the results of a plasma digoxin assay altered the dose which had already been selected on the basis of simple clinical assessment. No patient received more than 375 micrograms digoxin per day and none showed clinical evidence of toxicity even though seven had renal impairment. Six other patients had poorly controlled ventricular rates requiring larger doses of digoxin, but even in these patients the dose could be selected on clinical grounds alone. Despite the availability of a very rapid fluorescence polarisation immunoassay for digoxin, simple but careful clinical monitoring is an adequate basis for the selection of a suitable dose in most patients taking digoxin for atrial fibrillation. PMID- 4041297 TI - Plants and cardiac glycosides. PMID- 4041298 TI - Cultivation and breeding of Digitalis lanata in the Netherlands. AB - After the second world war Marshall Aid funds were used to establish a cooperative organisation for growing, drying, and selling Digitalis lanata (and other medicinal, aromatic, and culinary herbs) in the Netherlands. The crop is sown in mid April and the fully mechanised harvest of the leaves takes place from September to late November. The leaves are dried for 10-12 hours at 50 degrees C maximum. The aim of breeding trials is to improve leaf production, erect leaf attitude, resistance to Septoria leaf spot and to bolting, and a higher dry matter and digoxin content. PMID- 4041299 TI - Arrhythmogenic potential of diuretic induced hypokalaemia in patients with mild hypertension and ischaemic heart disease. AB - In view of evidence suggesting an association of mild hypokalaemia with cardiac arrhythmia, the arrhythmogenic potentials of potassium losing and potassium sparing diuretic treatments were compared in a controlled prospective crossover study of 10 patients with mild hypertension and ischaemic heart disease. Mean (SEM) plasma potassium was 4.3(0.06) mmol/l and 3.3(0.07) mmol/l after potassium sparing and potassium losing treatments respectively. Blood pressure and volume depletion as assessed by weight change, plasma renin activity, and noradrenaline concentrations did not differ significantly in the two treatment periods. The potassium losing treatment phase was associated with an increased frequency of ventricular extrasystoles, a higher Lown grading during ambulatory electrocardiographic monitoring, prolonged duration and decreased phase 0 velocity of the monophasic action potential, a prolonged ventricular effective refractory period, and increased myocardial electrical instability as assessed by programmed ventricular stimulation. It is concluded that minor changes in plasma potassium concentration are associated with increased ventricular electrical instability in patients with ischaemic heart disease. Mild hypokalaemia in such patients may predispose to life threatening arrhythmias and should be avoided. PMID- 4041300 TI - Acute haemodynamic and metabolic effects of dopexamine, a new dopaminergic receptor agonist, in patients with chronic heart failure. AB - Dopexamine, a new compound with postjunctional dopamine receptor activating and beta adrenoceptor agonist properties, was given to 10 patients with chronic heart failure at diagnostic cardiac catheterisation to investigate its acute haemodynamic and metabolic effects. The drug was administered by intravenous infusion in three incremental doses and produced significant dose related increases in cardiac index, stroke volume index, and heart rate and falls in systemic vascular resistance and left ventricular end diastolic pressure; aortic and pulmonary artery pressures were unchanged. Isovolumic phase (max dP/dt and KVmax) and ejection phase (peak aortic blood velocity, maximum acceleration of blood, and maximum rate of change of power with time during ejection) indices of myocardial contractility were all increased by dopexamine but these changes were hard to interpret in the presence of an increase in heart rate. Myocardial efficiency and ejection fraction were both increased and left ventricular end diastolic and end systolic volumes fell. These largely beneficial changes were achieved without a statistically significant increase in myocardial oxygen consumption or disturbance of myocardial metabolic function. Dopexamine was well tolerated but tremor was reported by two patients at the intermediate dose and mild chest pain by two patients at the high dose. PMID- 4041301 TI - Respiratory gas exchange in the assessment of patients with impaired ventricular function. AB - Respiratory gas exchange on exercise was evaluated as a non-invasive method of assessing patients with heart failure. Twenty four men (age 28-72) with symptomatic chronic stable heart failure (New York Heart Association class II III) and ten controls aged 36-70 were studied. During treadmill exercise oxygen consumption and carbon dioxide production were measured continuously by analysis of mixed expired gas with a computerised mass spectrometer. The anaerobic threshold was defined as the oxygen consumption at which carbon dioxide production increased disproportionately in relation to oxygen consumption. Oxygen consumption was stable at rest and increased on exercise, reaching a steady state within three minutes of any change in workload. The measurements of maximum oxygen consumption at the end of exercise and of anaerobic threshold were reproducible (retest reliability coefficients 90% and 91% respectively). There were significant differences in maximum oxygen consumption between functional classes. Similarly, there were significant differences in anaerobic threshold between classes, though there was considerable overlap. Measurement of oxygen consumption and anaerobic threshold provides an objective noninvasive assessment of patients with heart failure. PMID- 4041302 TI - Hypertrophic cardiomyopathy simulating an infiltrative myocardial disease. AB - Congestive heart failure developed in a patient with low electrocardiographic QRS voltages, diffuse thickening of the septum and free cardiac wall, and a reduction in left ventricular internal diameter, which suggested an infiltrative heart muscle disease. Histological examination at necropsy showed hypertrophic cardiomyopathy with symmetrical left ventricular hypertrophy. Myocardial disarray of type 1A disorganisation was extensive and equally distributed in the ventricular septum and the left anterior and left posterior ventricular free walls. Severe fibrosis (40%) was also present and may have been a possible cause of the electrocardiographic abnormalities as well as of the lack of ventricular dilatation. PMID- 4041303 TI - Management of aortic left ventricular tunnel. AB - A 22 year old man had a diagnosis of left ventricular aortic tunnel established during infancy. Surgical repair was deferred at that time because his severe aortic root deformity would also have required aortic valve replacement. His current lack of symptoms together with a normal exercise capacity could be used as an argument against routine early surgical repair of the tunnel, particularly when the possible need for additional aortic valve replacement is considered. PMID- 4041304 TI - Right atrial spleen. AB - A large cardiac tumour occupying most of the right atrium and the right ventricle and causing inflow obstruction to the right heart was confirmed by cross sectional echocardiography in a 41 year old man. After surgical resection histological examination showed that the atrial tumour had the characteristics of splenic tissue. Possible mechanisms for the development of such a tumour include an origin analogous to that of an accessory spleen or the implantation and subsequent growth of lymphoid tissue in a pre-existing superior vena caval or high right atrial angioma. PMID- 4041305 TI - Early prenatal detection of double outlet right ventricle by echocardiography. AB - A double outlet right ventricle with subpulmonary ventricular septal defect and right sided hypoplastic aorta was diagnosed in a 22 week fetus of a mother with diabetes mellitus. Elective termination of pregnancy was carried out and the echocardiographic findings were confirmed. Early prenatal detection of congenital heart disease may allow elective termination of pregnancy when the fetus has severe defects. PMID- 4041306 TI - Comparison of the vasoactivity of amide and ester local anaesthetics. An intradermal study. AB - The vascular effects and duration of action of two ester-linked local anaesthetics, procaine and amethocaine, and four amide-linked local anaesthetics, cinchocaine, lignocaine, mepivacaine and prilocaine, were investigated in 10 volunteers by intradermal injection using a double-blind technique. Procaine and amethocaine produced marked vasodilatation; weal formation was observed at 80% of the amethocaine injection sites. Mepivacaine had a marked vasoconstrictor effect; the other three agents produced more variable vasoactivity. Duration of action was concentration-dependent for all six drugs, the slopes of the log dose- duration plots reflecting the observed vasoactivity. PMID- 4041307 TI - Interactions between diltiazem and isoflurane. An in vitro investigation in isolated guinea pig atria. AB - Maximum force of contraction of paced, isolated guinea pig atria was measured in three groups. Atria from animals in group 1 were exposed to isoflurane for 10 min. In group 2, atria were exposed to diltiazem 35 nmol litre-1 alone and in group 3 atria were pre-treated with diltiazem 35 nmol litre-1 before exposure to isoflurane. Maximum depression of contraction was significantly greater in tissue exposed to the combination of diltiazem and isoflurane (group 3) compared with that exposed to isoflurane alone (group 1). Tissue exposed to diltiazem and isoflurane remained significantly more depressed from 15 to 30 min after the administration of isoflurane compared with the depression produced by the volatile agent alone. The results suggest that the calcium antagonist, diltiazem, may modify the effects of isoflurane on myocardial function. PMID- 4041309 TI - Paranasal sinusitis: a complication of nasotracheal intubation. Two case reports. AB - Reports are presented on two patients who developed severe paranasal sinusitis in association with prolonged nasotracheal intubation. The likely predisposing factors are discussed. PMID- 4041308 TI - Haemorrhage decreases the anaesthetic requirement for ketamine and thiopentone in the pig. AB - The anaesthetic requirements of ketamine and thiopentone were studied in eight pig littermates during normovolaemia and after haemorrhage (30% blood loss). Four animals received ketamine and four thiopentone, and the minimal anaesthetic doses of both drugs were determined. Moderate hypovolaemia decreased the anaesthetic requirements significantly and similarly: thiopentone 33 +/- 5%; ketamine 40 +/- 5% (mean +/- SEM). PMID- 4041310 TI - Paroxysmal electroencephalographic discharges during enflurane anaesthesia in patients with a history of cerebral convulsions. AB - The electroencephalogram (EEG) was monitored through all phases of enflurane anaesthesia in dental outpatients with a history of cerebral convulsions which had been well controlled with anticonvulsant drugs. Abnormal EEG activity which differed from the background activity was observed in three patients. Their case reports are presented. PMID- 4041311 TI - Laboratory diagnosis of malignant hyperpyrexia susceptibility (MHS). European MH Group. PMID- 4041312 TI - Duration of fast before elective surgery. PMID- 4041313 TI - Paracetamol kinetics and gastric emptying. PMID- 4041314 TI - Oral ranitidine in labour. PMID- 4041316 TI - Fixation of extradural catheters. PMID- 4041315 TI - Excretion of lorazepam into breast milk. PMID- 4041317 TI - Antagonism of neuromuscular blockade. PMID- 4041318 TI - Side effects induced by suxamethonium on the skeletal muscle and their prevention. PMID- 4041319 TI - Naloxone--a strong analgesic in combination with high-dose buprenorphine. PMID- 4041320 TI - Postoperative analgesia with Duromorph. AB - The analgesic effects and bioavailability of a slow-release preparation of morphine (Duromorph) were studied in 12 patients with acute postoperative pain. Duromorph produced significant analgesia within 1-2 h of administration i.m., and there was a progressive decrease in the mean pain score for at least 8 h. None of the patients requested or received additional analgesia within 12 h, and the incidence of side-effects was similar to that associated with i.m. morphine. During the 8-h study, plasma concentrations of morphine slowly increased for 3 h, and then gradually declined. After 3 h, concentrations were invariably greater than those produced by conventional doses of morphine sulphate i.m. The study confirmed that Duromorph was an effective analgesic with a prolonged duration of action, which was suitable for the management of postoperative pain. PMID- 4041321 TI - Baclofen prolongs the analgesic effect of fentanyl in man. AB - Pretreatment with baclofen prolonged the duration of fentanyl-induced analgesia from 18 to 30 min in patients undergoing neurosurgical anaesthesia (fentanyl plus nitrous oxide in oxygen). This observation is consistent with a potentiating effect of GABA on opioid analgesia. PMID- 4041322 TI - Evaluation of the combined effects of atropine and neostigmine on the lower oesophageal sphincter. AB - The effects, on the lower oesophageal sphincter, of the simultaneous administration of atropine and neostigmine were studied in 10 healthy patients undergoing gynaecological surgery. Atropine 1.2 mg and neostigmine 2.5 mg were given to antagonize neuromuscular blockade at the termination of surgery. For the succeeding 15-20 min, frequent measurements of lower oesophageal sphincter pressure (LOSP) were made whilst anaesthesia was maintained. It was demonstrated that this drug combination resulted in a significant decrease in LOSP initially, but that this potentially deleterious effect was transient in nature. PMID- 4041323 TI - A double-blind study of motor blockade in the lower limbs. Studies during spinal anaesthesia with hyperbaric and glucose-free 0.5% bupivacaine. AB - Sensory and motor blockade were studied double-blind during spinal anaesthesia in 20 urology patients who received 0.5% bupivacaine solution 4 ml with or without glucose. Using a new method for determining muscle strength, motor blockade during anaesthesia was recorded quantitatively for flexion of the hip, extension of the knee and plantar flexion of the big toe. Movements of the lower part of the thoracic cage were recorded at the same time. Complete motor blockade of longer duration was observed for all three movements following the administration of the glucose-free solution compared with the solution containing glucose. During the regression phase, the muscle strength returned significantly later (knee extension and hip flexion) when glucose-free bupivacaine solution was given. There was no significant difference between the two anaesthetic solutions regarding plantar flexion of the big toe during this phase. For hip flexion (L1 L3) there was no noteworthy difference between the levels of analgesia and the motor blockade, whereas for plantar flexion of the big toe (L5-S2) the level of analgesia was 2-3 segments higher than the level of motor blockade. Thoracic movements (maximal inspiration to normal expiration) did not appear to be notably influenced by the level of analgesia. Complete regression of motor blockade was not observed for any of the movements at grade O of a modified Bromage scale. Not until 1.5-2 h after the attainment of this grade was the muscle strength of all movements restored (90% of control value). PMID- 4041324 TI - Spinal anaesthesia with 0.75% bupivacaine and 0.5% amethocaine in 5% glucose. AB - Three millititre of 0.75% plain bupivacaine and 0.5% amethocaine 3 ml in 5% glucose were used for spinal anaesthesia and compared in a double-blind study of 20 patients undergoing urological surgery. The onset time to maximum cephalad spread of sensory analgesia was approximately 45 min for bupivacaine and approximately 30 min in the amethocaine group (ns). The mean maximum spread of sensory analgesia was similar for both agents: T6-7 180 min after injection, although the cephalad spread of sensory analgesia with bupivacaine persisted for longer at a significantly higher level than that of amethocaine. Duration of sensory analgesia was significantly longer in the bupivacaine group from S3 to S5 and from T12 to L2 levels. Onset time to complete motor blockade of the lower limbs was similar for both agents. Nine of 10 bupivacaine patients and seven of the 10 patients receiving amethocaine had complete motor blockade of the lower limbs. Duration of motor blockade was significantly longer for all degrees in the bupivacaine group. PMID- 4041325 TI - Thermoregulatory responses to cooling in patients susceptible to malignant hyperpyrexia. AB - The influence of 1 h of surface cooling on body temperature, variables which contribute to thermoregulation and selected hormones and metabolites has been investigated in seven patients susceptible to malignant hyperpyrexia (MH) and in seven matched control subjects. Cooling was achieved using a liquid conditioned coverall worn next to the skin. Skin temperature decreased similarly in both groups of subjects. Heat production increased in both groups, with a slightly higher heat production being seen in the MH group. Core temperature increased in both groups of subjects at the start of the cooling period, with a significantly greater increase occurring in the MH group (control: + 0.13 +/- 0.13; MH: + 0.28 +/- 0.10 degrees C, P less than 0.05). There were no significant changes in plasma lactate, or pyruvate concentrations. Plasma glucose concentrations were lower in the control group; after 30 min of cooling plasma glucose was 4.25 +/- 0.37 mmol litre-1 in the control group and 5.34 +/- 0.21 mmol litre-1 in the MH group (P less than 0.05). There were no significant changes in plasma thyroxine or adrenaline concentrations. Plasma noradrenaline increased in both groups of subjects. The increase in plasma noradrenaline of the MH patients was greater than in most of the control subjects. PMID- 4041326 TI - Microcalorimetric studies in malignant hyperpyrexia susceptible individuals. AB - In an attempt to develop a diagnostic test for malignant hyperpyrexia (MH) without the need for open muscle biopsy, we have investigated the change in heat production brought about when platelets and muscle are exposed to halothane and caffeine. Halothane 3% caused platelet aggregation, which was itself associated with heat production. Caffeine 4 mmol litre-1 decreased heat production in platelets from both MH susceptible and non-susceptible individuals. Muscle exposed to 4% halothane showed an increase in heat production in both types of tissue. There were no significant differences in heat production between MH susceptible and non-susceptible tissue in any of the tests. PMID- 4041327 TI - Diltiazem inhibits halothane-induced contractions in malignant hyperthermia susceptible muscles in vitro. AB - The ability of diltiazem to suppress halothane and halothane-caffeine induced contractures in malignant hyperthermia (MH) susceptible pig muscle, was tested in vitro. Muscle specimens were divided into two groups and tested with a modified halothane-caffeine contracture test. One group acted as the control; the other group was pretreated with diltiazem 20 mumol litre-1. The control muscles developed contractures attributable to halothane and halothane-caffeine, whereas the diltiazem-treated specimens did not. Increases in muscle twitch tension as a result of halothane or halothane-caffeine exposure occurred in treated and untreated specimens, but were significantly delayed in the presence of diltiazem. Muscle exhaustion observed after halothane and halothane-caffeine exposure in the control specimens did not occur in the diltiazem treated muscles. PMID- 4041328 TI - Dermal effects of compositions based on the eutectic mixture of lignocaine and prilocaine (EMLA). Studies in volunteers. AB - The effects of the cutaneous application of EMLA cream (a eutectic mixture of lignocaine and prilocaine in their base form) were studied in volunteers. When tested by pin-prick, EMLA cream 2.5% and 5% produced analgesia of the area tested, the cream being most effective if left in contact with the skin for 60 min. The pain produced by the insertion of an i.v. cannula was successfully blocked by the application of this formulation, especially if applied to the antecubital area. Temporary blanching of the skin areas was frequently observed on removal of the occlusive tape bandages, but prolonged, or repeated, application of 5% EMLA cream did not produce local skin reactions. Tests for delayed hypersensitivity reactions were negative. Plasma concentrations of lignocaine and prilocaine were low after a standard application. PMID- 4041329 TI - Verapamil pharmacokinetics and apparent hepatic and renal blood flow. AB - The effect of acute and continued administration of verapamil on pharmacokinetics and regional blood flow has been studied in eight normotensive subjects. Continued administration resulted in a significant decrease in verapamil clearance, compared to that following acute dosing, as assessed by increases in both terminal elimination half-life (from a mean +/- s.d. of 5.2 +/- 2.3 h to 6.7 +/- 2.0 h) and AUC (from a mean +/- s.d. of 800 +/- 353 ng ml-1 h to 1455 +/- 244 ng ml-1 h). The relative clearance of norverapamil was not changed. Acute administration of verapamil resulted in a significant increase (P less than 0.005) in apparent liver blood flow which with continued administration fell significantly (P less than 0.01) towards placebo values. Effective renal plasma flow similarly increased with acute verapamil administration (P less than 0.05) and with chronic administration reduced again to be not significantly different from placebo. Acute and chronic verapamil administration did not significantly alter glomerular filtration rates. These results suggest that there may be a relationship between the acute increase in liver blood flow and the relatively increased clearance of verapamil following acute dosing. PMID- 4041330 TI - Anticonvulsant therapy and cortisol elimination. AB - The effect of anticonvulsant therapy on early morning concentration of cortisol in saliva and plasma was assessed in a group of epileptic patients receiving regular phenytoin medication and the results compared with those obtained from a group of normal subjects not receiving drug therapy. Values of cortisol in matched samples of plasma (331 +/- 23 nmol l-1, mean +/- s.e. mean, n = 6) and saliva (11.4 +/- 0.9 nmol l-1, mean +/- s.e. mean, n = 9) provided by epileptics did not differ significantly from those in the plasma (334 +/- 41 nmol l-1, mean +/- s.e. mean) and saliva (12.0 +/- 2.0 nmol-1, mean +/- s.e. mean) of healthy volunteers (n = 12). Six anticonvulsant-treated epileptics, together with six age and sex matched normal volunteers, each received intravenous dexamethasone (1 mg h-1) to determine the half-life of cortisol in plasma and saliva. In the anticonvulsant-treated group, the half-life of cortisol in plasma (73 +/- 5 min, mean +/- s.e. mean) and saliva (83 +/- 5 min, mean +/- s.e. mean) was reduced significantly (P less than 0.01 plasma, P less than 0.05 saliva) from that observed in healthy volunteers. In patients, the half life of cortisol and antipyrine showed a significant correlation (r2 = 0.75, P less than 0.05 plasma, r2 = 0.71, P less than 0.05 saliva). The antipyrine half-life in saliva was reduced significantly (P less than 0.02) and the antipyrine clearance rate, increased significantly (P less than 0.005) in the treated epileptic group, reflecting drug-induced microsomal enzyme production.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4041331 TI - The effects of long-acting pinacidil on intra-arterial blood pressure. AB - We have tested the efficacy of a new long-acting preparation of pinacidil, an arterial vasodilator, using continuous intra-arterial ambulatory blood pressure recording. An acute dose produced a measurable effect lasting for 12 h. The duration of this effect was less during chronic twice daily drug administration. Side effects were common, causing two out of nine patients to withdraw from the study. Tilt testing produced no postural hypotension and there was no evidence of rebound hypertension on the withdrawal day. PMID- 4041332 TI - Effects of long-acting propranolol on blood pressure and heart rate in hypertensive Chinese. AB - In a double-blind, balanced and randomised study we used treadmill exercise to assess the effects of long-acting propranolol (LA propranolol) 160 or 320 mg or placebo, given once daily for 4 weeks, on heart rate (HR) and blood pressure (BP) in 15 Chinese subjects with mild primary hypertension (PHT). We used 24 h ECG monitoring to assess drug effects on HR. Another 18 patients were similarly assessed without exercise. Steady-state plasma propranolol concentrations after LA propranolol 160 and 320 mg were comparable to those after ordinary propranolol 80 and 160 mg daily measured in 11 and 12 separate patients. LA propranolol 160 and 320 mg reduced HR and BP before and during vigorous exercise. LA propranolol 160 and 320 mg reduced HR for 17.6 and 21.4 h of the day, and 320 mg significantly reduced the mean 24 h HR, and the mean maximum HR. The drug effects on BP and HR, and the average plasma propranolol levels after LA propranolol were similar to those reported in European subjects. PMID- 4041333 TI - Haemodialysis does not affect the pharmacokinetics of nifedipine. AB - To establish dosage recommendations in patients with end-stage renal disease undergoing chronic haemodialysis, nifedipine kinetics were studied between and during haemodialysis sessions. In eight patients, during the interdialytic period, peak plasma concentrations of nifedipine (29-332 ng/ml) were reached 0.5 1.0 h after administration of a single 10 mg oral dose. Elimination half-life and oral plasma clearance were respectively 2.6 +/- 0.5 h and 1 176 +/- 412 ml/min. Nifedipine plasma protein binding was decreased in uraemic patients (88.8 +/- 0.3% vs 94.4 +/- 0.1%) but not affected by haemodialysis. Removal by haemodialysis was low: the dialyser extraction ratio and the dialysis clearance were respectively 2.3 +/- 0.8% and 2.8 +/- 0.9 ml/min. PMID- 4041334 TI - Effects of single and multiple doses of ketoconazole on adrenal function in normal subjects. AB - The plasma cortisol response to 0.25 mg tetracosactrin given by intramuscular injection was suppressed by nine oral doses of 200 mg ketoconazole given 12 hourly to nine normal female subjects. No effect was noted following a single 200 mg oral dose of ketoconazole. This suppressive effect was reversible within at least 5 days of discontinuation of ketoconazole. PMID- 4041335 TI - Pharmacokinetics of ranitidine in quadriplegics. AB - In a previous study we observed that quadriplegic patients were unresponsive to ranitidine given in high dose (600 mg day-1 intravenously) for prophylaxis of stress ulceration. The pharmacokinetics of 100 mg of intravenous ranitidine have therefore been studied in six male quadriplegic patients. Plasma drug concentrations declined in a biexponential fashion. The mean (+/- s.e. mean) distribution half-life was 9.42 (+/- 1.04) min. The terminal plasma elimination half-life 1.79 (+/- 0.12) h, the volume of distribution 103 (+/- 17) litres and total body clearance 663 (+/- 86) ml/min. These values are similar to those described in two published studies performed in normal male volunteers. This suggests that there is no pharmacokinetic reason for the quadriplegics to be resistant to ranitidine and the defect is likely to be related to vagal control of acid secretion. PMID- 4041336 TI - The effect of ranitidine on the disposition of lignocaine. AB - The effect of pretreatment with ranitidine (150 mg twice daily for 5 days) on the disposition of lignocaine was examined in 10 healthy volunteers (five male, five female). Each subject received separate oral (250 mg) and intravenous (1.5 mg/kg) doses of lignocaine hydrochloride before and after ranitidine. Lignocaine systemic clearance was reduced by 9% (1.11 to 0.99 1 h-1 kg-1; P less than 0.01) following ranitidine pretreatment. The volume of distribution at steady-state was reduced by 15% (3.34 to 2.85 1 kg-1; P less than 0.005). Lignocaine oral clearance, elimination half-life and oral bioavailability were unchanged after ranitidine pretreatment. There was no sex difference in the effects of ranitidine pretreatment on lignocaine disposition. These results are consistent with small reductions in blood flow to the splanchnic and other vascular beds due to ranitidine. PMID- 4041338 TI - A model which predicts maintenance warfarin dosage requirements from the response to a single dose. PMID- 4041337 TI - Effect of short surgical procedures on salivary paracetamol elimination. AB - The effect of short surgical procedures on paracetamol elimination was studied in seven male patients undergoing surgery with epidural anaesthesia. Five healthy volunteers who did not undergo surgery served as a control group. Paracetamol concentration was measured in saliva at various intervals 1 day before and after surgery. Paracetamol half-life (t1/2,z) decreased and metabolic clearance rate (CL) increased after surgery as compared to preoperative values. The results suggest that surgical stress may enhance the hepatic metabolism of paracetamol. PMID- 4041339 TI - Consequences of inflammatory processes on lignocaine protein binding during anaesthesia in fibreoptic bronchoscopy. PMID- 4041340 TI - Ranitidine and procainamide absorption. PMID- 4041341 TI - Ventilatory effects of long-term treatment with pindolol and metoprolol in hypertensive patients with chronic obstructive lung disease. AB - Effects of long-term treatment with pindolol (10 mg twice daily) and metoprolol (100 mg twice daily) on lung function and blood pressure were investigated in eight patients with chronic obstructive lung disease and hypertension. After a placebo period, both beta-adrenoceptor blockers were administered double-blind and cross-over for 4 weeks. By assessing parameters of expiratory flow an attempt was made to distinguish between large and small airways function. Diastolic blood pressure decreased significantly during both pindolol and metoprolol (P less than 0.01). Except for a decrease in forced expiratory volume in 1 s (FEV1) during metoprolol treatment, there was no other change in expiratory flow parameters after placebo or both beta-adrenoceptor blockers. Inhalation of terbutaline induced a small improvement in large airways function after placebo and metoprolol, but not after pindolol; there was no effect of terbutaline on parameters of small airways function. If a beta-adrenoceptor blocker is necessary in patients with chronic obstructive lung disease, a beta 1-adrenoceptor selective blocker is preferred in combination with bronchodilator agents. PMID- 4041342 TI - Selectivity and dose-dependency of the inhibitory effect of propranolol on theophylline metabolism in man. AB - The effects of separate 5 day pretreatments of propranolol 120 mg day-1 and 720 mg day-1 on theophylline clearance and metabolism at steady-state were determined in seven healthy males. Propranolol 120 mg day-1 decreased theophylline plasma clearance (CL) by 30%. Clearance of theophylline to each metabolite was reduced by this treatment, clearances to the two demethylated products by 42-43% and clearance to the 8-hydroxylation product by 27%. Propranolol 720 mg day-1 decreased theophylline CL by 52%. Again, clearance of theophylline to each metabolite was reduced by this treatment, clearances to the two demethylation products by 73-77% and clearance to the 8-hydroxylation product by 44%. These data are consistent with a dose-dependent and selective inhibitory effect of propranolol on the separate forms of cytochrome P-450 involved in theophylline demethylation and 8-hydroxylation. PMID- 4041343 TI - The influence of diflunisal on the pharmacokinetics of oxazepam. AB - Single dose pharmacokinetics of oxazepam, 30 mg, have been studied in six healthy male volunteers in the absence of diflunisal and during continuous treatment with diflunisal 500 mg twice daily. During diflunisal treatment, peak plasma concentration of oxazepam significantly decreased from 387 +/- 18 ng ml-1 (mean +/- s.e. mean) to 241 +/- 10 ng ml-1 and total area under the plasma concentration-time curve (AUC) significantly decreased from 5536 +/- 819 ng ml-1 h to 4643 +/- 562 ng ml-1 h. The AUC of oxazepam glucuronide significantly increased from 4771 +/- 227 ng ml-1 h to 8116 +/- 644 ng ml-1 h and its elimination half-life increased from 10.0 +/- 0.6 h to 13.0 +/- 1.0 h. Renal clearance for oxazepam glucuronide was significantly reduced from 74 +/- 2 ml min 1 to 46 +/- 3 ml min-1. In vitro, diflunisal, at concentrations of 125 to 1000 micrograms ml-1, significantly displaced oxazepam from its plasma protein binding, the free fraction of oxazepam increasing by 28 to 56%. The free fraction of oxazepam glucuronide, ex vivo, increased by 49 +/- 5% (n = 3) during concomitant diflunisal treatment. These data suggest that the observed interaction between oxazepam and diflunisal results from a presystemic displacement of oxazepam from its plasma protein binding sites by diflunisal and from an inhibition of the tubular secretion of oxazepam glucuronide by the glucuronides of diflunisal. PMID- 4041344 TI - The effect of nisoldipine on apparent liver blood flow and effective renal plasma flow. AB - The effects of the acute and continued administration of the calcium antagonist nisoldipine on hepatic and renal blood flow and on renal function were studied in nine normotensive volunteers. There were no significant changes in supine blood pressure or heart rate but acute administration significantly increased both apparent liver blood flow and effective renal plasma flow. With continued administration these increases were attenuated and were not significantly different from placebo after 4 days treatment. Acute nisoldipine administration was also associated with significant increases in glomerular filtration rate and urinary sodium excretion. PMID- 4041345 TI - The share of the elderly men and women in the commonest causes of death. PMID- 4041346 TI - Supraventricular arrhythmias--digoxin and quinidine revisited. PMID- 4041347 TI - The surgical treatment of thyroid disease in a district general hospital. PMID- 4041348 TI - Home-monitoring of blood glucose--patient preference for 'BM-Test Glycemie 20 800' strips or 'Glucometer'. PMID- 4041349 TI - A comparison of Antraderm stick 1% and 2% with dithranol paste 0.25% and 0.5% respectively in the treatment of psoriasis. PMID- 4041350 TI - Benylin expectorant versus actifed expectorant in the treatment of acute cough. PMID- 4041351 TI - Spastic paraparesis with cirrhosis of liver. PMID- 4041352 TI - Avascular necrosis of the coccyx: a cause of coccydynia? Case report and histological findings in 16 patients. PMID- 4041353 TI - Fatal retroperitoneal bleeding following Latamoxef (Moxalactam) use. PMID- 4041355 TI - Infertility management in the 'eighties. PMID- 4041354 TI - Malabsorption and polymyositis in a case of congenital methaemoglobinaemia. PMID- 4041356 TI - Complications of non-absorbable ligatures in thyroid surgery. PMID- 4041357 TI - Seat belts and breast disease. PMID- 4041358 TI - A comparative trial of urinary incontinence aids. PMID- 4041359 TI - Soft agarose culture human tumour colony forming assay for drug sensitivity testing: [3H]-thymidine incorporation vs colony counting. AB - In vitro drug sensitivity testing, both by optical colony counting and by a [3H] TdR incorporation assay, was performed on human tumour cells proliferating in soft agar cultures. Cells from two different human tumour cell lines, 5 different human tumour xenografts, and 94 different primary human tumour specimens of various histologic types were studied. Regression analysis comparing the results of the colony counting assay and the [3H]-TdR assay revealed good to excellent correlations between the two assay endpoints for quantitating the effect of in vitro anticancer drug exposure for a large number of different agents. The presence of pre-existing tumour cell aggregates complicates the performance of the optical colony counting assay. The [3H]-TdR incorporation assay is more sensitive and reproducible than the colony counting assay when performed on samples containing a large number of initially seeded tumour cell aggregates. PMID- 4041360 TI - Non-linearity of colony formation by human tumour cells from biopsy samples. AB - The relationship between colony numbers and concentration of cells plated is an important parameter of clonogenic assay systems. The cloning efficiency for an ideal sample should be independent of cell concentration, thus giving a straight line through the origin when colony numbers are plotted against cell concentration. A simple statistical method has been developed to test if this is the case for individual tumour samples. Colony data from 51 freshly obtained tumour samples, which had sufficient cells to plate 3 or more dilutions and gave at least 20 colonies per plate at one or more of the dilutions, were tested. The results indicated that colony formation was linear for 27 (53%) of the samples. The remaining 24 samples could be classified into 2 groups: type I, in which cloning efficiencies increased with increasing cell concentration and type II, which had reduced cloning efficiencies at high cell concentrations. Fifteen (29%) of the samples had type I non-linearity and 9 (18%) exhibited non-linearity of type II. These findings indicate that the relationship between colonies and cells plated should be examined for each biopsy sample particularly in each experiment where the effects of cytotoxic drugs are tested. PMID- 4041362 TI - Lung cancer 1978-1981 in the black peoples of South Africa. AB - Mortality data on lung cancer among the black populations of South Africa, newly available from the first ever nation-wide enumerations, are analysed for age specific rates and significant geographical and intertribal variations. This study finds a higher incidence at younger ages than among whites, an urban excess similar to other population groups in South Africa and a higher incidence among the Xhosa than Zulu. It is suggested that an anti-smoking campaign is urgently required among blacks in South Africa. PMID- 4041361 TI - Radiation dose and second breast cancer. AB - Amongst 14,000 women with breast cancer treated between 1946 and 1982, 194 developed a second primary tumour in the contralateral breast more than one year after diagnosis of the first primary. The radiation dose to the contralateral breast was calculated for each member of this group and also for members of a control group matched for age, year of diagnosis and survival time. Comparison of the groups provides no evidence for radiation induced carcinogenesis on the contralateral breast in these patients. PMID- 4041363 TI - Cytotoxicity of etretinate and vindesine. AB - The effects of an aromatic retinoid, etretinate and a vinca alkaloid, vindesine were investigated by culture of malignant melanoma cells in vitro with these two agents; either separately or in combination. Etretinate inhibited growth of a murine melanoma but only minimal effects were recorded with two human melanomas. Vindesine however, was inhibitory for all of the cell lines and this effect was enhanced in the presence of the retinoid. Entry of 3H labelled vindesine or etretinate into drug free cells was followed in the absence or presence of unlabelled drug. It was found that etretinate enhanced cellular uptake of vindesine in two of the cell lines and this may be responsible for the enhanced toxicity of vindesine in the presence of etretinate. The human melanoma which did not exhibit retinoid stimulated vindesine uptake, appeared to be intrinsically sensitive to the vinca alkaloid. No effect on cellular retinoid uptake by vindesine was recorded in any of the melanomas. The results indicate that the intracellular concentrations combined with the intrinsic sensitivities of each cell line to etretinate and vindesine determines the toxic response. PMID- 4041364 TI - Adrenergic factors regulating cell division in the colonic crypt epithelium during carcinogenesis and in colonic adenoma and adenocarcinoma. AB - Evidence exists implicating adrenergic factors in the control of intestinal epithelial cell proliferation in both normal and diseased states. In this report, attention is focussed on changes in the amine requirements of proliferating cells during the chemical induction of tumours in the colon of mouse. Cell proliferation rates were measured stathmokinetically. Tumours were induced by s.c. injection of dimethylhydrazine (DMH). Results with a series of adrenoceptor agonists and antagonists suggest that there is an alpha 2-adrenoceptor mediated excitatory effect in normal colon but an alpha 2 adrenoceptor mediated inhibitory effect in adenoma and carcinoma. Alpha 1 adrenoceptors, on the other hand, have an inhibitory effect in normal crypts and in adenomas, and an excitatory effect in carcinomas. Beta adrenoceptors have an inhibitory effect in the normal and DMH treated crypt, and in adenomas, but not in carcinomas. In the crypt epithelium of DMH-treated mice, two regions on cell proliferation, with differing regulatory factors, could be identified. In the upper region of the carcinogen-exposed crypt is a zone where cell proliferation is stimulated by an alpha 2 adrenergic mechanism, thus resembling the basal region of the normal crypt. By contrast, in the basal region of these crypts, cell proliferation is stimulated by an alpha 1 mechanism, thus resembling a malignant tumour. PMID- 4041365 TI - On the clonality of tumours. PMID- 4041366 TI - Twenty-sixth annual general meeting of the British Association for Cancer Research (in conjunction with the European Organization for Research and Treatment for Cancer--Pharmacokinetics and Metabolism Group and the Drug Metabolism Group). March 24-27, 1985, Birmingham, U.K. PMID- 4041367 TI - Bone marrow biopsy findings in angioimmunoblastic lymphadenopathy. AB - Bone marrow biopsies from 13 cases of lymph-node-biopsy-proven angioimmunoblastic lymphadenopathy (AILD) were studied. Eight cases (62%) showed a characteristic 'granulomatoid' lymphoreticular infiltrate composed of a mixture of lymphocytes, epithelioid histiocytes, immunoblasts, plasma cells and eosinophils in varying proportions. Proliferation of blood vessels, although much less prominent than that described in lymph nodes, and a marked degree of reticulin fibrosis were also noted. The pattern of involvement was mainly focal and rarely diffuse. The foci were either single or multiple, and were distributed throughout the marrow but were only rarely paratrabecular. The associated haematopoietic marrow findings were nonspecific regardless of degree of bone marrow involvement. The histopathology of involved bone marrows in angioimmunoblastic lymphadenopathy is such that in some cases it should strongly suggest the diagnosis even in the absence of a prior definitive lymph node biopsy. Differentiating features from other disorders that might be confused with AILD are discussed. Survival rate was adversely affected by bone marrow involvement. PMID- 4041368 TI - Evaluation of serum deoxythymidine kinase as a marker in multiple myeloma. AB - A recently developed deoxythymidine kinase assay utilizing 125I-iododeoxyuridine as substrate was used in an investigation of sera from 122 untreated patients with multiple myeloma. Most patients had slightly elevated or normal serum deoxythymidine kinase activity (S-TK), although in some patients values increased by more than forty-fold were found. S-TK correlated with the haemoglobin level but did not correlate with sex, age, erythrocyte sedimentation rate, nor with the serum concentrations of creatinine, beta 2-micro-globulin, Ca or M-component. The distribution of S-TK values in IgG, IgA and pure Bence-Jones myeloma did not differ significantly. Patients with IgG and IgA myeloma excreting light-chain immunoglobulin in the urine had significantly higher S-TK than non-excreters. There was a significant correlation between S-TK values and tumour cell mass as determined by clinical staging. A high pretreatment S-TK (greater than 5.1 units) also distinguished a group of patients with a significantly shorter survival time. Patients with no response to initial therapy had significantly higher S-TK values than those who did respond. In longitudinal studies of 11 patients, S-TK was found to increase when the disease became more aggressive. The possibility of diagnosing disease progression at an early stage by an elevation of S-TK is discussed. PMID- 4041369 TI - Daunomycin administered by continuous intravenous infusion is effective in the treatment of acute nonlymphocytic leukaemia. AB - Anthracyclines given by continuous infusion, as opposed to bolus administration, are associated with a reduced incidence of cardiac and gastrointestinal toxicity. Our study was developed to test the antileukaemic effect of anthracyclines given as a continuous infusion. Nineteen sequential patients admitted for treatment of acute nonlymphocytic leukaemia (ANLL) were managed with a regimen utilizing a 3 d continuous intravenous infusion of daunomycin (DNM), and the complete response rate was similar to this institution's past experience with antileukaemic regimens employing 3 d bolus DNM. In our studies, infusion DNM was at least as myelotoxic and antileukaemic as bolus DNM; thus this method of administration should be explored further in remission-induction regimens for ANLL. PMID- 4041370 TI - Cyclosporin A in the treatment of severe acute aplastic anaemia. AB - Twelve consecutive adults with severe acute aplastic anaemia, not having a bone marrow transplantation option, were prospectively randomized to receive either cyclosporin A alone or an equivalent amount of this immunosuppressive agent in combination with antilymphocyte serum. The minimum follow-up is 36 months, with half the patients developing nephrotoxicity, which was easily reversible in all but one. No response could be attributed to either regimen. Cyclosporin A does not appear to have a place as primary form of treatment for adults with severe acute aplastic anaemia, either on its own or in combination with antilymphocyte serum. PMID- 4041371 TI - Regulation of erythropoiesis during rapid growth. AB - High levels of plasma erythropoiesis stimulating factor(s) (ESF) have been found in neonatal WLO-mice during the period of rapid growth. If the high ESF activity is due to the concomitant physiological anaemia of infancy alone, it should be possible to block erythropoiesis by hypertransfusion. Mice were hypertransfused starting on day 14, and killed on day 20. Although hypertransfusion reduced the ESF levels by approximately 55% (P less than 0.001), ESF levels were still detectable in the cell culture assay used (P less than 0.001). Moreover, hypertransfused mice showed active erythropoiesis in the bone marrow, and none had a reticulocyte count below 2%. No correlation was found between PCV and ESF in the hypertransfused animals (r = 0.07, P greater than 0.5), nor was there any difference in weight gain between control and hypertransfused mice (P greater than 0.5). These results show that hypertransfusion did not totally supress erythropoiesis in neonatal WLO-mice, which is different from hypertransfused adult mice. The data indicate that the high plasma ESF found in neonatal WLO-mice during the growth period are not due to the anaemia alone. These findings support studies indicating that regulation of erythropoiesis in the neonate differs from the adult. Factors related to growth per se could be responsible for this difference. PMID- 4041372 TI - Human mononuclear phagocyte differentiation: a study of the U-937 cell line by ultrastructural cytochemistry and surface antigen analysis. AB - U-937 represents a well-established permanent human haematopoietic cell line, which exhibits characteristics of the monocyte/macrophage series. U-937 cells were investigated by peroxidase ultrastructural cytochemistry in order to determine the normal developmental stage to which they correspond. This study was performed in non- and TPA-stimulated cells, in conjunction with surface analysis by monoclonal antibodies. It is concluded: (1) peroxidase-positive U-937 cells are monoblasts and promonocytes involved in myeloperoxidase synthesis; (2) TPA stimulation caricatures transformation of these cells into monocytes but not into resident macrophages, as far as peroxidase cytochemistry is concerned; (3) the reactivity of myeloperoxidase present in the endoplasmic reticulum of synthesizing cells is inhibited by glutaraldehyde fixation. PMID- 4041373 TI - In vitro erythropoietin assay based on erythroid colony formation in fetal mouse liver cell culture. AB - Critical studies were made on erythroid colony formation from cultured fetal mouse liver cells in an attempt to develop a simple and sensitive erythropoietin (Epo) assay procedure. The maximum colony formation was observed 24 h after plating of the cells when an evident dose-response relation was found for Epo added. The colony forming ability decreased steadily as the gestational age of the fetus advanced and was gradually lost by postnatal days 10-11. By morphological and cytochemical criteria almost all the colonies were found to be erythroid. 59Fe-labelling experiments revealed a fairly good correlation between the colony number and 59Fe incorporation into both cells and haem. Dose-response curves for plasma were parallel to the Epo standard curve. Based on these findings we developed a procedure which could measure as little as 0.4 mU of Epo without requiring 59Fe. Using this method, plasma Epo titres were determined in 16 normal and 69 anaemic subjects. PMID- 4041374 TI - Endogenous origin of microbiologically-inactive cobalamins (cobalamin analogues) in the human fetus. AB - The cobalamin content of placenta, maternal and fetal sera was assayed by methods which measure microbiologically-active and microbiologically-inactive cobalamins. Only microbiologically-active cobalamins were present in the placenta but both types were present in both maternal and fetal circulations. We conclude that only microbiologically-active cobalamins cross the placenta and that the microbiologically inactive cobalamins in the fetus must arise by metabolism in situ. PMID- 4041375 TI - A novel form of factor VII in plasma from men at risk for cardiovascular disease. AB - In the Northwick Park Heart Study high activity of the coagulation factor VII was associated with cardiovascular deaths. We confirm here that men at high risk for such disease have increased levels of factor VII activity and demonstrate for the first time that this is due to a phospholipid-factor VII complex in their plasma. This complex increases the specific activity of its factor VII significantly. It is not inhibited by a neutralizing antiserum to thromboplastin and thus does not represent a factor VII-thromboplastin complex. Gel filtration data suggest an apparent Mr of 66-72 000 for the complex. Factor VII in this phospholipid complex is more sensitive than native factor VII to the serine protease inhibitor diisopropyl-fluorophosphate, consistent with a more accessible active site conformation (and a higher specific activity) for factor VII in the complex. The level of phospholipid-factor VII complex showed a significant positive correlation with plasma triglycerides and correlation of borderline significance with cholesterol. PMID- 4041376 TI - Characterization of an occult inhibitor to factor IX in a haemophilia B patient. AB - Six haemophilia B patients were studied while undergoing infusion with factor IX concentrate. All were negative for factor IX antigen (IX:AG) and inhibitor to factor IX coagulant activity (IX:C). One patient showed an atypical response pattern, with prolonged survival of IX:C and IX:Ag. This patient remained under prophylactic treatment and more than 1 year later developed an inhibitor to IX:C of clinical significance. Retrospective study revealed that this patient had significantly higher levels of circulating immune complexes than other haemophilia B patients and in vivo formation of immune complexes containing IX:Ag prior to detection of his inhibitor in conventional clotting assays, suggesting long-term persistence of an occult inhibitor. The inhibitor was shown to be an IgG antibody with both kappa and lambda light chains. PMID- 4041377 TI - Idiopathic combined immunocytopenia. AB - Four patients with combined immunocytopenia of unknown origin were investigated. Two patients with pancytopenia had allo- and autoantibodies against erythrocytes, granulocytes and thrombocytes. Two other patients with granulocytopenia and thrombocytopenia showed allo- and autoantibodies against granulocytes and thrombocytes. All patients went into a transient or persistent remission under immunosuppressive therapy. The normalization of peripheral blood correlated with the disappearance of antibodies suggesting that the cytopenia was caused by an antibody mediated autoimmune mechanism. PMID- 4041378 TI - Autoimmune disease in hairy-cell leukaemia: clinical syndromes and treatment. AB - Thirty-seven patients with hairy-cell leukaemia were retrospectively reviewed for the presence of autoimmune disease. Ten definite and two probable cases were identified; these patients had positive serologies (immune complexes, antinuclear antibodies or rheumatoid factor) or biopsy-proven vasculitis. Clinically, two distinct syndromes were recognized. Six patients had joint symptoms, usually associated with nodular skin lesions; all responded promptly to therapy. Four additional cases had a more severe disease consisting of fevers, malaise, weight loss, skin rash, and variable visceral involvement; there was one death in this group. There appeared to be no relationship between presence of vasculitis and the severity or progression of the underlying malignant disease. We conclude that autoimmune disease is much more frequent in hairy-cell leukaemia than has previously been recognized, and that the outcome in these syndromes is usually good. Although the autoimmune syndrome generally responds promptly to splenectomy, corticosteroids, or cytotoxic therapy, failure to recognize this complication may lead to increased morbidity and occasional mortality. PMID- 4041379 TI - Classification of anaemia on the basis of ferrokinetic parameters. AB - Quantitative information on abnormalities of erythropoiesis and mechanisms of anaemia has been obtained in 136 anaemic patients by means of ferrokinetic studies. To derive a functional classification of anaemia based on ferrokinetic parameters, agglomerative hierarchical cluster analysis and principal coordinate analysis were utilized as techniques for unsupervised classification. Two main clusters were found and named anaemia with low potential erythropoiesis and with high potential erythropoiesis, since the most discriminant parameter between them was total erythroid iron turnover, a measure of total erythropoietic activity. A value of total erythropoiesis equal to 4 times the normal was found to discriminate these two types of anaemia in 94% of cases. Within the group with low potential erythropoiesis, three clusters showing different qualitative disturbances of erythropoiesis were singled out. Among patients with high potential erythropoiesis, two clusters were found. A value of effective erythropoiesis equal to 2.5 times the normal was shown to have a high discriminant power between these clusters. This threshold level distinguished between patients having ineffective erythropoiesis or peripheral haemolysis as the major mechanism of anaemia. The present functional classification of anaemia provides a complete picture of the different pathogenetic mechanisms and may represent the basis for a more rational diagnostic approach to erythroid disorders. PMID- 4041380 TI - Further observation on post-transfusion purpura (PTP) PMID- 4041381 TI - Health assessment of applicants for nurse training. PMID- 4041382 TI - Cancer mortality of cadmium workers. AB - Several epidemiological studies of workers exposed to cadmium indicate an increased risk of lung and prostatic cancer. The increase is statistically significant in some of the studies but the SMR is greater than 100 in almost all. A cohort study of the mortality among 522 Swedish workers exposed to cadmium for at least one year in a nickel-cadmium battery plant support the earlier findings. The SMR for lung and prostatic cancer increased with increasing dose and latency but did not obtain statistical significance. A combination of all the available data from the most recent follow up of causes of death among cadmium workers in six different cohorts shows 28 cases of prostatic cancer (SMR = 162) and 195 cases of lung cancer (SMR = 121). This new analysis suggests that long term, high level exposure to cadmium is associated with an increased risk of cancer. The role of concomitant exposure to nickel needs further study. PMID- 4041383 TI - Job load and hazard analysis: a method for the analysis of workplace conditions for occupational health care. AB - One requirement for successful occupational health care is reliable information on occupational hazards. The aim of this study was to develop a simple, standardised method for workplace investigations for use in occupational health care. The theoretical framework of the method comprises the stress-strain model, the hazard-danger model, and risk behaviour theory. The new method, termed job load and hazard analysis, includes four stages: identification of hazards, their evaluation, conclusions and proposals, and follow up. Different methods are available for hazard identification. The identification starts with a rough analysis of five factors, chemical hazards, physical hazards, physical load, mental stress, and accident risk. Hazards and stress factors are assessed with an ordinal scale. Specialised methods are used if all hazards cannot otherwise be identified. The analytical procedure comprises: detection of hazards through observations and interviews at the workplace and with a questionnaire; assessment of findings as teamwork; and evaluation of the results of these assessments to yield conclusions and proposals made by occupational health care personnel. A data processing system has been developed for data storage and future use. The method has functioned in practice, improving the contents of the occupational health care programme and generating preventive measures. The method offers many new possibilities for controlling occupational hazards and studying relations between working conditions and workers' health. PMID- 4041384 TI - A study of white finger in the gas industry. AB - Men engaged in breaking or reinstating road surfaces are exposed to vibration from mechanical tools. In view of the lack of epidemiological information on vibration white finger in such a population, a survey was carried out to identify the prevalence of symptoms of white finger in a sample of men using these tools in the gas industry and to compare the prevalence with that found in a control group not occupationally exposed to vibration. Altogether 905 men (97%) in the gas industry and 552 men (92%) in the control group were interviewed, using a questionnaire from which the presence or absence of white finger symptoms from all causes was noted. The prevalence of white finger was 9.6% in the group exposed to vibration at work compared with 9.5% in the control group. The prevalence in the former group when adjusted for age differences between the survey and control populations was 12.2%, but this difference did not reach statistical significance. In case the approach of comparing prevalences of white finger from all causes might have obscured any contributory effect of vibration, the prevalence of white finger was examined in relation to the number of years vibrating tools had been used, this being the only measure of exposure to vibration available. No direct association was found between the prevalence of symptoms and number of years vibrating tools had been used. In view of this and the absence of a significant excess of white finger symptoms in the group using vibratory tools, the authors conclude that vibration white finger is not a special problem in the gas industry. Nevertheless, experimental tests carried out on the different types of roadbreakers used in the industry and on different road surfaces indicate that the vibration levels exceed the standards advocated in the draft international standard DIS 5349 (1979) at the lower end of the frequency spectrum. That no particular problem has been found may be due to the relatively short exposures to vibration experienced by the operators or the fact that they are able to grip the tools lightly, or even, possibly, that the standards suggested in DIS 5349 do not accurately reflect the risk of vibration white finger when they are exceeded at the lower end of the frequency spectrum for vibrating tools such as roadbreakers. PMID- 4041385 TI - Influence of local vibration on plasma creatine phosphokinase (CPK) activity. AB - This study was designed to obtain basic information about the mechanism of the occurrence of muscular disorders after exposure to vibration. The hind legs of rats were exposed to acute and chronic local vibration at frequencies of 30, 60, 120, 240, 480, and 960 Hz with a constant acceleration of 50 m/sec2. The exposure time was four hours for acute, and four hours a day for two weeks continuously for chronic exposure. Blood was collected after exposure to measure plasma creatine phosphokinase (CPK) activity. In both exposure groups the activity of plasma CPK was significantly higher at 30, 60, 120, 240, and 480 Hz compared with the control group and was especially high at 30 Hz; there was no significant change at 960 Hz. As a result of an analysis of the CPK isoenzymes, the increase in plasma CPK activity was shown to be due to the activity of the plasma CPK-MM fraction, originating in the skeletal muscle. Plasma CPK activity showed a tendency to decrease gradually with the increase in vibration frequency during acute exposure but showed no such tendency during chronic exposure. There was no remarkable pathohistological change in muscle preparations from the hind legs, hence it was presumed that the increase in plasma CPK activity was caused not by the morphological changes of muscle but by other mechanisms, such as an increase in the permeability of the cell membrane. PMID- 4041386 TI - Diethyllead as a specific indicator of occupational exposure to tetraethyllead. AB - In a group of 26 workers exposed to tetraethyllead a correlation was found between the concentration of tetraethyllead in the air and the concentration of diethyllead (r = 0.70) and total lead (r = 0.84) in the urine and also between the excretion of diethyllead and total lead (r = 0.68). The results obtained indicate that diethyllead may be used as a specific indicator of occupational exposure to tetraethyllead. PMID- 4041388 TI - Does acute toxicity testing tell us anything useful? Methyl isocyanate as a test case. PMID- 4041387 TI - An outbreak of illness after occupational exposure to ozone and acid chlorides. AB - New labelling processes installed without adequate ventilation control in an electric motor factory exposed production line workers to toxic gases. Symptoms of eye and respiratory tract irritation together with complaints of headache, fever, chills, dizziness, malaise, general weakness, nausea, and vomiting were widespread. Chest signs, radiographic abnormalities, reduction in ventilatory function, and blood gas abnormalities were found in some cases. Epidemiological analysis of the spatial and temporal distribution of cases supported an exposure effect relationship. Investigations suggested ozone and possibly phosgene and associated trichloroacetyl chlorides as the toxic agents that were generated by an ultraviolet print curing arrangement and perchloroethylene used as a cleaning solvent. PMID- 4041389 TI - Lung function measurements over 21 days shiftwork in steelworkers from a strandcasting department. AB - On the assumption that short term changes in lung function may reflect the potential for a long term decline the evolution of lung function indices in 25 steelworkers from a strandcasting department and in 11 comparable steelworkers not exposed to dust was investigated over an almost uninterrupted 21 day working period and over three different workshifts. The mean total dust level in the strandcasting department, assessed by personal sampling, was 11.8 mg/m3. All subjects were examined at the beginning, in the middle, and at the end of their first (day 1) morning shift (0600 to 1400), their last (day 14) afternoon shift (1400 to 2200), and their last (day 21) night shift (2200 to 0600). Indices measured were vital capacity (VC), forced expiratory volume in one second (FEV1) and in three seconds (FEV3), forced expiratory flow over the middle half of the forced vital capacity (FEF25-75), peak expiratory flow rate (PEFR), the slope of the N2 plateau (delta N2) and the closing volume (CV) of the single breath oxygen test. Differences in indices between initial values (0600 on day 1) and final values (0500 on day 21) were not significant in the control group (except delta N2 which became lower); in the casting group there were significant (p less than 0.05) decreases in FEF25-75 and FEV3, but these decreases were not significantly greater than in the control group. Lung function changes were not significant in either group over the morning shift. During the afternoon there were significant decreases in spirometric indices in the casting group, with no significant decreases in the control group, but the interactions between exposure and time were generally not significant. During the night shift, however, the decreases in FEV1 and FEF25-75 observed in the strandcasting group were significantly more pronounced than in the control group. The single breath test, which many subjects failed to perform correctly on each occasion, showed no significant changes in closing volumes, and an "improvement" of delta N2 over the morning and the night shift in the control but not the exposed subjects needs to be interpreted with caution. The more pronounced decrease in spirometric indices, suggestive of slight airways obstruction, found over the night shift in the strandcasting workers is attributed to their working environment. PMID- 4041391 TI - Gastric cancer in coal miners: a case-control study in a coal mining area. AB - In collaboration with three pathology departments a case-control study was conducted in the southern part of the Netherlands to investigate the risk of gastric cancer in coal miners. Between 1 January 1973 and 31 December 1983, 323 male patients were diagnosed as having a malignant neoplasm of the stomach. For each case a control was selected from the same pathology department, matched on year of birth and regardless of diagnosis. The archives of the Central Coal Miners Pension Fund were searched to obtain information about whether or not a patient had ever worked for a coal mining company in the Netherlands. Twenty two per cent of the patients had been registered as an underground coal miner, compared with 20% of the control group (odds ratio of 1.14, 95% confidence interval: 0.33-1.73). Those with gastric cancer who had ever worked underground in a coal mine did so for an average period of 16.9 years compared with an average of 19.7 years in the control group. The study gives no indication that the underground workers of the Dutch coal mines had a raised risk of developing a malignant neoplasm of the stomach. PMID- 4041392 TI - Quantitative mineralogical analysis of small samples of china clay using x ray diffractometry. AB - The quantitative mineralogical analysis of small samples (less than 20 mg) of china clay has been investigated using x ray diffractometry to determine kaolinite, mica, quartz, and feldspar. A method has been developed and applied to the quantitative analysis of airborne dust samples and of other small discrete samples. Determinations were made either on samples after collection on a membrane filter or on samples after deposition from aqueous suspension on to a silver substrate. Quantitative analysis was hindered by preferred orientation of the kaolinite and of the mica particles that occurs when using these methods of specimen preparation. Quartz and feldspar were determined direct from prepared calibration graphs. Preferred orientation of the mica particles leads to serious interference with the most sensitive quartz x ray diffraction peak which, if not recognised, will result in an overestimation of the quartz content. Kaolinite and mica were determined from the ratio of their most intense x ray diffraction peak areas to overcome the preferred orientation effects observed for these two minerals. During the investigation, the opportunity arose for comparative measurements of quartz contents of airborne dust samples with the Occupational Medicine and Hygiene Laboratories of the Health and Safety Executive. The mass of specimen examined varied between 0.8 mg and 20 mg and the quartz contents varied between 0.1% and 1.2%. The comparative results were in good agreement. PMID- 4041390 TI - Protective effect of selenium on lung cancer in smelter workers. AB - A possible protective effect of selenium against lung cancer has been indicated in recent studies. Workers in copper smelters are exposed to a combination of airborne selenium and carcinogens. In this study lung tissue concentrations of selenium, antimony, arsenic, cadmium, chromium, cobalt, lanthanum, and lead from 76 dead copper smelter workers were compared with those of 15 controls from a rural area and 10 controls from an urban area. The mean exposure time for the dead workers was 31.2 years, and the mean retirement time after the end of exposure 7.2 years. Lung cancer appeared in the workers with the lowest selenium lung tissue levels (selenium median value 71 micrograms/kg wet weight), as compared with both the controls (rural group, median value 110; urban group, median value 136) and other causes of death among the workers (median value 158). The quotient between the metals and selenium was used for comparison: a high quotient indicating a low protective effect of selenium and vice versa. The median values of the quotients between antimony, arsenic, cadmium, lanthanum, lead, chromium, and cobalt versus selenium were all numerically higher among the cases of lung cancer, the first five significantly higher (p less than 0.05) in 28 of the 35 comparisons between the lung cancer group and all other groups of smelter workers and controls. The different lung metal concentrations for each person were weighted according to their carcinogenic potency (Crx4 + Asx3 + Cdx2 + Sbx1 + Cox1 + Lax1 + Pbx1) against their corresponding selenium concentrations. From these calculations the protective effect of selenium was even more pronounced. PMID- 4041393 TI - Dissolution of metals by human and rabbit alveolar macrophages. AB - The ability of human and rabbit alveolar macrophages to dissolve 0.1-0.5 micron MnO2 particles in vitro was compared. The amount of Mn added and dissolved from the particles over periods of nought, one, and three days was determined by flame atomic absorption spectrophotometry. The amount dissolved by human and rabbit macrophages was similar; on average 43.1% and 43.9%, respectively, were dissolved within three days. But rabbit and human macrophages dissolved significantly more Mn than was dissolved in the respective culture medium without macrophages after one and three days. It is suggested that the dissolution of particles by alveolar macrophages should be one basic component in any model of alveolar clearance of inorganic particles. PMID- 4041394 TI - Risk factors for radiogenic cancer: a comparison of factors derived from the Hanford survey with those recommended by the ICRP. PMID- 4041395 TI - Zinc deficiency is not a cause for abortion, congenital abnormality and small-for gestational age infant in Chinese women. AB - Zinc concentration in serum and hair was measured in a cross-sectional study of 437 Chinese women of whom 310 were normal controls studied at various stages of pregnancy and up to 12 months after delivery. The rest had spontaneous abortions, fetuses with a birthweight below the 10th centile for gestation or congenital abnormalities. Zinc concentration fell throughout normal pregnancy, the fall being greater in serum than in hair. There was no correlation between serum and hair levels. The infant birthweight had a positive correlation with serum level but a negative correlation with hair level. Abortion, low birthweight and congenital abnormality were not associated with low concentrations of zinc in plasma or hair. PMID- 4041396 TI - The effects of oral iron supplementation on zinc and magnesium levels during pregnancy. AB - Serial changes in serum zinc and magnesium concentrations have been studied before conception, throughout pregnancy and at 12 weeks postpartum in 15 normal healthy women not receiving iron supplementation, 10 women receiving iron supplementation but otherwise having healthy pregnancies and five insulin dependent diabetics who also received oral iron. Relative to pre-pregnancy values zinc concentrations progressively decreased throughout pregnancy reaching a nadir at 36 weeks gestation followed by an increase; pre-pregnancy values were achieved by 12 weeks postpartum. Magnesium concentrations also decreased throughout pregnancy reaching a nadir at 32 weeks gestation increasing thereafter again with pre-pregnancy values achieved by 12 weeks postpartum. Iron supplementation in non diabetic and diabetic women had no significant effect upon the changes in serum concentration of either zinc or magnesium. These results suggest that the decrease in the concentrations of both elements is a normal physiological adjustment to pregnancy and that iron supplementation does not influence these changes. PMID- 4041397 TI - Fetal blood chromosome analysis: some new indications for prenatal karyotyping. AB - Prenatal karyotyping using stimulated fetal blood lymphocytes was undertaken in 170 pregnancies between 16 and 36 weeks gestation for the following reasons- mosaicism or marker chromosomes found in amniotic fluid culture; a family history of X-linked mental retardation with fragile Xq28; fetal abnormalities detected ultrasonographically; late booking or amniotic fluid culture failure in patients with advanced age or balanced translocations; and twin pregnancies discordant for a chromosomal anomaly. Forty-one karyotypic abnormalities were detected (24%). These were: 45,X (7 cases), trisomy 13 (5 cases), trisomy 18 (6 cases), trisomy 21 (4 cases), twin pregnancy where one twin had trisomy 21 (1 case), supernumerary marker chromosome (3 cases, one of which occurred in a twin pregnancy), triploidy (3 cases), X-linked mental retardation with fragile site at Xq28 in males (6 cases), fetal erythroleukaemia (3 cases including 2 cases with Turner's), Fanconi's anaemia (1 case), unbalanced chromosome translocation 47,XY+der22,t(11;22) mat (1 case), mos 46,XX18p-/46,XX,-18+i(18q) (1 case), 46,XXdel(2q) (1 case), and 46,XYt(5;17) de novo (1 case). In fetuses at high risk of a chromosome aberration, a rapidly obtained karyotype is helpful and fetoscopy and fetal blood sampling are justified in the second or third trimester. PMID- 4041398 TI - The repetition of spontaneous preterm labour. AB - The likelihood of repetition of preterm birth after spontaneous onset of labour has been studied in 6572 reproductive careers after excluding stillbirths, multiple births, all careers in which any labour had been induced, and all careers in which the gestation length in any pregnancy was not certain. The analysis was controlled not only for pregnancy number, but for the nature of the reproductive outcomes. In most reproductive sequences there was a weak correlation between the gestation in one pregnancy and subsequent ones. The risk of preterm birth was tripled after one previous preterm birth with or without a preceding abortion, and increased six-fold after two previous preterm births. However, the attributable risk was low, and most multiparae with preterm births did not have a previous history. PMID- 4041399 TI - The assessment of persistent bradycardia in prenatal life. AB - Twelve patients with persistent fetal bradycardia were referred for echocardiographic assessment; in 10 patients the fetus had complete heart block, six isolated and four with associated structural heart disease. In the remaining two patients an atrial arrhythmia was producing a fetal sinus bradycardia. Complete heart block with structural heart disease has a poor prognosis. Isolated complete heart block has a good prognosis if the pregnancy is carefully managed. A sinus bradycardia due to atrial ectopic beats is a benign arrhythmia. Echocardiographic assessment of the heart can give an accurate prognosis in fetal bradycardia and provide a basis for appropriate obstetric management. PMID- 4041401 TI - The outlook for women with borderline epithelial tumours of the ovary. AB - Seventy-two women with borderline epithelial tumours of the ovary have been followed up for between 3 and 9 years. Patients with disease confined to one or both ovaries had a good prognosis, irrespective of histological type. When extra ovarian spread was present at the time of diagnosis, neither the histological type nor the amount of residual tumour predicted the long-term outcome in individual patients. PMID- 4041400 TI - Gestation sac size in in-vitro fertilization pregnancies. AB - The gestation sac size in pregnancies resulting from in-vitro fertilization (IVF) and embryo transfer have been compared with those in spontaneous pregnancies. Small-for-dates gestational sac sizes were found in 36% of the IVF pregnancies. This proportion held for both singleton and multiple pregnancies. With increasing gestation beyond 8 weeks the gestation sac volume increasingly approached normal. In contrast to spontaneous conceptions, IVF pregnancies had a low rate of pregnancy loss once fetal heart movements were demonstrated, when the gestation sac size was small-for-dates. Small sac size in an IVF pregnancy may lead to the misdiagnosis of a failed pregnancy. PMID- 4041403 TI - Entrapment of the fetal head in a unilateral imperforate vagina in association with complete duplication of uterus and cervix. Case report. PMID- 4041402 TI - Spironolactone in combination with an oral contraceptive: an alternative treatment for hirsutism. AB - The clinical efficacy of a combination of spironolactone and an oral contraceptive pill (Conova 30) was assessed in 23 patients presenting with hirsutism of whom 20 completed 6 months of treatment. Of the 20 patients, 16 showed improvement on objective (Ferriman & Gallwey hair score) and subjective assessment. Serum levels of androgens (testosterone, androstenedione and 17 hydroxy progesterone) were suppressed and sex hormone binding globulins were elevated. Nausea was the only significant side effect. PMID- 4041404 TI - Beware of the 'plum'--ureterocele. Case report. PMID- 4041405 TI - Pancreatic lipase and phospholipase A2 concentration in amniotic fluid and the prenatal diagnosis of cystic fibrosis. PMID- 4041406 TI - Obstetric aspects of Gaucher's disease. PMID- 4041407 TI - The sex ratio of infants born after hormonal induction of ovulation. PMID- 4041408 TI - Rapid, reliable diagnosis of chlamydial ophthalmia by means of monoclonal antibodies. AB - The use of fluorescein-conjugated monoclonal antibody (Syva, UK) provided a rapid reliable diagnostic test for Chlamydia trachomatis in conjunctival samples from 100 adults with acute follicular conjunctivitis and seven babies with suspected chlamydial ophthalmia neonatorum. Elementary bodies (EBs) were seen in smears from 11 of the adults, and culture confirmed C. trachomatis infection in nine of them. Both tests were positive with specimens from four of the neonates. No specimens from either group of patients produced a negative result in the smear test but a positive result by culture. However, the two adult patients with chlamydial ophthalmia who had negative cultures but were EB-positive had both had prior topical tetracycline therapy. PMID- 4041409 TI - Treatment of experimental lens capsular tears with intense focused ultrasound. AB - High-intensity focused ultrasound was employed to seal lens capsular tears in a rabbit model. Ultrasound therapy was applied either contiguously, thereby completely covering the tear, or in a discrete exposure pattern around the tear. Both methods prevented the formation of a generalised cataract. This was in contrast to results observed in a group of control (untreated) animals which all developed generalised lens opacities. Each control animal also developed a local lens opacity at the site of the capsular tear, as did half the animals treated with the discrete pattern. No animal treated with contiguous exposures developed any local or generalised traumatic-type cataract other than the small lens opacity immediately produced by the treatment. These treatment cataracts would not constitute a significant impediment to vision so long as they did not fall on the visual axis. PMID- 4041410 TI - Retinal detachment following extracapsular cataract extraction and posterior chamber intraocular lens implantation. AB - Fourteen cases of primary retinal detachment after extracapsular cataract extraction and posterior chamber intraocular lens implantation were treated by scleral buckling surgery. Retinal reattachment was achieved in 100% of the cases. All eyes had a postoperative visual acuity of 6/30 or better; in six eyes the visual acuity was 6/12 or better. We attributed our high anatomical success rate to early detection of the retinal detachment, good visibility of the retinal breaks, lack of inflammatory reaction in the vitreous body, and preoperative absence of fixed retinal folds and preretinal membranes. PMID- 4041411 TI - Shifting subretinal fluid in rhegmatogenous retinal detachment. AB - In a consecutive series of 470 cases of rhegmatogenous retinal detachment 25 (5%) were found to have shifting subretinal fluid (SRF) at the preoperative examination. The study showed that the association between SRF and rhegmatogenous retinal detachment is unusual but not rare. Shifting SRF was most often associated with aphakic and longstanding retinal detachment, and found in cases in which the retinal holes were small. PMID- 4041412 TI - Changes at the periphery of a lesion in necrotising scleritis: anterior segment fluorescein angiography correlated with electron microscopy. AB - Anterior segment fluorescein angiography in scleral disease reveals highly characteristic changes in the vasculature of the anterior segment associated with necrotising scleritis. The vaso-obliterative changes discovered in this investigation have been correlated with the histopathology in a patient who had to have tissue replaced. Light and electron microscopy of scleral tissue excised from sites of vascular closure detected by fluorescein angiography peripheral to the scleral defect revealed pathological changes in the absence of inflammatory cell infiltration. These changes included vascular stasis, partial vaso obliteration, and fibroblastic transformation of scleral fibrocytes in association with intra- and extracellular degradation of the collagenous component of the matrix. PMID- 4041413 TI - Family studies in glaucoma. AB - Two groups of patients with a family history of chronic open-angle glaucoma were compared with a normal population of 5919 individuals studied during the Bedford Glaucoma Survey. The mean screening intraocular pressure was significantly raised in both groups with a family history of chronic open-angle glaucoma. The prevalence rate of a raised intraocular pressure was 3.81 times that found in the normal population. This relationship was maintained when age-dependent prevalence rates were evaluated. No correlation between raised intraocular pressure and type of familial involvement could be determined. A 10- to 12-year follow-up of one group with a family history for open-angle glaucoma (101 patients) showed that 3% developed confirmed glaucoma, while an additional 5.9% were diagnosed as suspected chronic open-angle glaucoma. A letter survey of this group showed that 9 out of 63 respondents knew of additional family members who developed glaucoma over this 10-12-year period. PMID- 4041414 TI - The ocular pulse and intraocular pressure as a screening test for carotid artery stenosis. AB - The ocular pulse and applanation tension were measured with a recording applanation tonometer in 38 patients suspected of having internal carotid artery stenosis. Abnormalities of the ocular pulse amplitude, intraocular pressure, or combinations of these two measurements were found in 23 (82%) of 28 patients who were subsequently found to have angiographic evidence of 50% or more stenosis of one or both internal carotid arteries. Of 10 patients without angiographic evidence of carotid stenosis the ocular pulse amplitude, intraocular pressure, or both were abnormal in five, but two patients had an ocular cause for abnormality and two of the remaining three had evidence of carotid disease in the form of atheromatous plaques. These results suggest that measurement of the amplitude of the ocular pulse in addition to the intraocular pressure can predict the presence of carotid artery stenosis and indicate the need for further investigation. If a tonometer capable of measuring the pulse amplitude was used routinely in ophthalmic examinations, it would provide a useful screening test for the early diagnosis and treatment of carotid artery disease and might thereby reduce the frequency of strokes. PMID- 4041415 TI - Transient monocular obscuration--?amaurosis fugax: a case report. AB - A 73-year-old white man with pseudophakia experienced repeated bouts of transient visual loss associated with erythropsia and colour desaturation. A diagnosis of atheromatous carotid vascular disease was considered, prompting carotid angiography, during which time the patient experienced transient aphasia. Subsequent examination during an episode of visual loss showed that a spontaneous anterior chamber haemorrhage was the cause of the visual complaints. PMID- 4041416 TI - Bilateral macular dysplasia ('colobomata') and congenital retinal dystrophy. AB - Three unrelated patients with bilateral macular dysplasia ('colobomata') with no relevant family history were found to have absent or substantially abnormal electroretinograms, implying that there was an associated retinal dystrophy. This may suggest that the macular lesions are associated with a global failure of retinal development, with a regional preponderance rather than a purely localised cause such as an intrauterine infection. It is important to distinguish between congenital infections such as toxoplasmosis and developmental macular colobomata, which have a somewhat similar ophthalmoscopic appearance as a cause of bilateral macular abnormalities seen in young children, since they have different implications for genetic advice and future ophthalmic care. PMID- 4041418 TI - Congenital fistulae of the lacrimal gland. AB - A 15-year-old female was found on routine clinical examination to have bilateral asymptomatic congenital fistulae of the lacrimal glands. The fistulae opened into the conjunctival sac at the external canthus of both eyes. Temporary occlusion of these openings produced an immediate and significant reduction in tear secretion in both eyes. PMID- 4041417 TI - Recurrent visual loss in homozygous sickle cell disease. AB - In sickle cell retinopathy vascular involvement is most frequently recognised at the retinal periphery, but obstruction of perimacular arterioles and of major retinal vessels may also occur. This report describes a patient with homozygous sickle cell (SS) disease with recurrent occlusion of major retinal vessels associated with recurring transient impairment of visual function. PMID- 4041419 TI - Proton nuclear Overhauser effect investigation of the heme pockets in ligated hemoglobin: conformational differences between oxy and carbonmonoxy forms. AB - Proton nuclear Overhauser effect (NOE) measurements have been used extensively to investigate the detailed conformations of peptides, proteins, and nucleic acids in the solution state. However, much of the published work has dealth with molecules of molecular weight less than 15 000. It is generally thought that specific NOEs cannot be observed in larger molecules (due to spin diffusion), so that NOE is of little use in conformational studies of such systems. By use of truncated-driven NOE with an irradiation time of 100 ms, specific NOEs are observed in a protein of the size of human normal adult hemoglobin (Hb A, 65 000 daltons). This technique has permitted us to assign several proton proton resonances arising from heme groups and from amino acid residues situated in the vicinity of the ligand binding site (such as E7 histidine and E11 valine) of the alpha and beta chains of Hb A. In addition, two-dimensional 1H[1H] J-correlated spectroscopy (COSY) experiments as well as theoretical ring-current calculations have confirmed the spectral assignments obtained by the one-dimensional NOE experiments. These new results not only have permitted us to map the heme pockets and to investigate the conformational differences in the heme pockets between oxy and carbonmonoxy forms of Hb A but also have demonstrated that the technique of truncated-driven NOE can be used to investigate the detailed conformations of selected regions in larger macromolecules in a way heretofore thought not to be feasible. PMID- 4041420 TI - NMR relaxation of protein and water protons in diamagnetic hemoglobin solutions. AB - We have measured T1 and T2 of protein and water protons in hemoglobin solutions using broad-line pulse techniques; selective excitation and detection methods enabled the intrinsic protein and water relaxation rates, as well as the spin transfer rate between them, to be obtained at 5, 10, and 20 MHz. Water and protein T1 data were also obtained at 100 and 200 MHz for hemoglobin in H2O/D2O mixtures by using commercial Fourier-transform instruments. The T1 data conform to a simple model of two well-mixed spin systems with single intrinsic relaxation times and an average spin-transfer rate, with each phase recovering from a radio frequency excitation with a biexponential time dependence. At low frequencies, protein T1 and T2 agree reasonably with a model of dipolar relaxation of an array of fixed protons tumbling in solution, explicitly calculating methyl and methylene relaxation and using a continuum approximation for the others. Differing values in H2O and D2O are mainly ascribed to solvent viscosity. For water-proton relaxation, T1, T2, and spin transfer were measured for H2O and HDO, which enabled a separation of inter-and intramolecular contributions to relaxation. Despite such detail, few firm conclusions could be reached about hydration water. But it seems clear that few long-lived hydration sites are needed to explain T1 and T2, and the spin-transfer value mandates fewer than five sites with a lifetime longer than 10(-8) s. PMID- 4041421 TI - Effects of human fibrinogen and its cleavage products on activation of human plasminogen by streptokinase. AB - The influence of human fibrinogen (Fg) and its terminal plasminolytic digestion products, fragment D and fragment E, on the kinetics of activation of human plasminogen (Pg) by catalytic levels of streptokinase (SK) has been investigated. Both Fg and fragment D enhanced the rates of activation of human Glu1-Pg, Lys77 Pg, and Val442-Pg. Fragment E was refractive in this regard. In the case of Glu1 Pg, the Km for activation by SK, 0.4 microM, was not affected by the presence of Fg or fragment D. The kcat for this same reaction, 0.12 s-1, was elevated to 0.3 s-1 at saturating levels of these effector molecules. On the other hand, the Km for activation of Lys77-Pg, 0.5 microM, was decreased to 0.09 microM, whereas the kcat, 0.33 s-1, was not altered in the presence of saturating concentrations of Fg or fragment D. In the case of Val442-Pg, the Km for this same activation, 2.0 microM, was lowered to 0.4 microM and 0.25 microM in the presence of Fg and fragment D, respectively. The kcat for this process, 1.0 s-1, was unchanged in the presence of these agents. The concentrations of Fg (KFg) and fragment D (KFD) that led to half-maximal stimulation of the activation rates were determined. For Fg with Glu1-Pg, Lys77-Pg, and Val442-Pg, the KFg values were 0.08 microM, 0.14 microM, and 0.17 microM, respectively. The KFD values for these same plasminogens were 0.25 microM, 2.0 microM, and 1.7 microM, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4041422 TI - Pressure-induced conformational changes in a human Bence-Jones protein (Mcg). AB - The effect of high static pressures on the internal structure of the immunoglobulin light chain (Bence-Jones) dimer from the patient Mcg was assessed with measurements of intrinsic protein fluorescence polarization and intensity. Depolarization of intrinsic fluorescence was observed at relatively low pressures (less than 2 kbar), with a standard volume change of -93 mL/mol. The significant conformational changes indicated by these observations were not attributable to major protein unfolding, since pressures exceeding 2 kbar were required to alter intrinsic fluorescence emission maxima and yields. Fluorescence intensity and polarization measurements were used to investigate pressure effects on the binding of bis(8-anilino-naphthalene-1-sulfonate) (bis-ANS), rhodamine 123, and bis(N-methylacridinium nitrate) (lucigenin). Below 1.5 kbar the Mcg dimer exhibited a small decrease in affinity for bis-ANS (standard volume change approximately 5.9 mL/mol). At 3 kbar the binding activity increased by greater than 250-fold (volume change -144 mL/mol) and remained 10-fold higher than its starting value after decompression. With rhodamine 123 the binding activity showed an initial linear increase but plateaued at pressures greater than 1.5 kbar (standard volume change -23 mL/mol). These pressure effects were completely reversible. Binding activity with lucigenin increased slightly at low pressures (standard volume change -5.5 mL/mol), but the protein was partially denatured at pressures greater than 2 kbar. Taken in concert with the results of parallel binding studies in crystals of the Mcg dimer, these observations support the concept of a large malleable binding region with broad specificity for aromatic compounds.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4041423 TI - 13C NMR study of the ionizations within a trypsin-chloromethyl ketone inhibitor complex. AB - 13C NMR is used to detect ionizations within a trypsin-chloromethyl ketone inhibitor complex. The pKa values observed are compared with those predicted by free-energy relationships. For the denatured/autolyzed inhibitor complex, a pKa = 5.26 is observed, which is assigned to the ionization of the imidazole of histidine-57. For the intact inhibitor complex a pKa = 7.88 is determined. This pKa is assigned to the ionization of the hemiketal hydroxyl (pKa = 7.88-8.1) and provides the first direct evidence that the serine proteases are able to stabilize the oxyanion of tetrahedral adducts. Indirect evidence is adduced that the imidazole pK1 of histidine-57 is greater than or equal to 8.1. Line broadening studies suggest that there may be extra fast exchange line broadening, which could result from rapid tautomeric exchange between neutral and zwitterionic species within the inhibitor complex. The significance of these results for the catalytic mechanism of serine proteases is discussed. PMID- 4041424 TI - Structure of metal-nucleotide complexes bound to creatine kinase: 31P NMR measurements using Mn(II) and Co(II). AB - The structures of metal-nucleotide complexes bound to rabbit muscle creatine kinase have been studied by making measurements of paramagnetic effects of two dissimilar activating paramagnetic cations, Mn(II) and Co(II), on the spin relaxation rates of the 31P nuclei of ATP and ADP in these complexes. The experiments were performed on enzyme-bound complexes, thereby limiting the contributions to the observed relaxation rate to two exchanging complexes (with and without the cation). Measurements were made as a function of temperature in the range 5-35 degrees C and at three 31P NMR frequencies, 81, 121.5, and 190.2 MHz, in order to determine the effect of exchange on the observed relaxation rates. The relaxation rates in E X MnADP and E X MnATP are independent of frequency, and their temperature variation yields activation energies (delta E) in the range 5-8 kcal/mol; in the transition-state analogue complex E X MnADP X NO3- X Cre (Cre is creatine), delta E is increased to 17.3 kcal/mol. These results demonstrate that the relaxation rates in the Mn(II) complexes are exchange limited and are incapable of providing structural data. It is shown further that use of line-width measurements to estimate the lifetime of the paramagnetic complex leads to incorrect results. The relaxation rates in E X CoADP and E X CoATP exhibit frequency dependence and delta E values in the range 1-3 kcal/mol; i.e., these rates depend on the Co(II)-31P distances, whereas those in the E X CoADP X NO3- X Cre complex have delta E approximately 18 kcal/mol and are significantly contributed by exchange.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4041425 TI - Interaction of zinc ions with arsanilazotyrosine-248 carboxypeptidase A. AB - The interaction between arsanilazotyrosine-248 carboxypeptidase A ([(Azo-CPD)Zn]) and excess zinc ions has been studied by stopped-flow and spectrophotometric methods at pH 8.2 and 7.7, I = 0.5 M (NaCl), and 25 degrees C. When excess zinc ions bind to arsanilazotyrosine-248 carboxypeptidase A, the characteristic red color, which arises from the intramolecular complex of the arsanilazotyrosine-248 residue with the active site zinc of the enzyme, changes to yellow with the inhibition of peptidase activity of the enzyme. Excess zinc ions have two binding sites for arsanilazotyrosine-248 carboxypeptidase A, and the binding constants of the first site (3.9 X 10(5) M-1 at pH 8.2; 7.1 X 10(4) M-1 at pH 7.7) are much larger than those of the second site (1.8 X 10(3) M-1 at pH 8.2; 7 X 10(2) M-1 at pH 7.7). The binding of excess zinc ions to the first site is completely correlated with the inhibition of the enzyme peptidase activity and the color change of the enzyme. The results can be understood in terms of zinc ions reacting with only one of three conformational states of arsanilazotyrosine-248 carboxypeptidase A [Harrison, L. W., Auld, D. S., & Vallee, B. L. (1975) Proc. Natl. Acad. Sci. U.S.A. 72, 4356].(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4041426 TI - Mitochondrial nicotinamide nucleotide transhydrogenase: active site modification by 5'-[p-(fluorosulfonyl)benzoyl]adenosine. AB - Membrane-bound and purified mitochondrial energy-linked nicotinamide nucleotide transhydrogenase (TH) was inhibited by incubation with 5'-[p (fluorosulfonyl)benzoyl]adenosine (FSBA), which is an analogue of TH substrates and their competitive inhibitors, namely, 5'-, 2'-, or 3'-AMP. NAD(H) and analogues, NADP, 5'-AMP, 5'-ADP, and 2'-AMP/3'-AMP mixed isomers protected TH against inhibition by FSBA, but NADPH accelerated the inhibition rate. In the absence of protective ligands or in the presence of NADP, FSBA appeared to modify the NAD(H) binding site of TH, because, unlike unmodified TH, the enzyme modified by FSBA under these conditions did not bind to an NAD-affinity column (NAD agarose). However, when the NAD(H) binding site of TH was protected in the presence of 5'-AMP or NAD, then FSBA modification resulted in an inhibited enzyme that did bind to NAD-agarose, suggesting FSBA modification of the NADP(H) binding site or an essential residue outside the active site. [3H]FSBA was covalently bound to TH, and complete inhibition corresponded to the binding of about 0.5 mol of [3H]FSBA/mol of TH. Since purified TH is known to be dimeric in the isolated state, this binding stoichiometry suggests half-of-the-sites reactivity. A similar binding stoichiometry was found earlier for complete inhibition of TH by [14C]DCCD [Phelps, D.C., & Hatefi, Y. (1984) Biochemistry 23, 4475-4480]. The active site directed labeling of TH by radioactive FSBA should allow isolation of appropriate peptides for sequence analysis of the NAD(H) and possibly the NADP(H) binding domains. PMID- 4041427 TI - Effect of ethanol on mucus glycoprotein fatty acyltransferase from gastric mucosa. AB - The enzyme activity that catalyzes the transfer of palmitic acid from palmitoyl coenzyme A to the deacylated intact or deglycosylated gastric mucus glycoprotein was demonstrated in the detergent extracts of the microsomal fraction of antral and body mucosa of the rat stomach. Both types of mucosa exhibited similar acyltransferase activities and acceptor specificities. A 10-14% decrease in the fatty acyltransferase activity was observed with the reduced and S carboxymethylated mucus glycoprotein, but the proteolytically degraded glycoprotein showed no acceptor capacity. This indicated that the acylation of mucus glycoprotein with fatty acids occurs at its nonglycosylated polypeptide regions and that some of the fatty acids may be linked via thiol esters. Optimum enzyme activity was obtained at pH 7.4 with the detergent Triton X-100, NaF, and dithiothreitol. The apparent Km values for the intact and deglycosylated mucus glycoproteins were 0.45 and 0.89 microM, respectively. The acyltransferase activity of the microsomal enzyme was inhibited by ethanol. With both intact and deglycosylated glycoprotein substrates, the rate of inhibition was proportional to the ethanol concentration up to 0.4 M and was of the competitive type. The K1 values were 0.80 microM for the intact mucus glycoprotein and 1.82 microM for the deglycosylated glycoprotein. Preincubation of the microsomal enzyme with low concentrations of ethanol (up to 0.5 M) did not seem to exert any additional deterrent effect on acyltransferase activity. Higher concentrations of ethanol (1.0 M and above), however, caused substantial reduction in the transferase activity due to denaturation of the enzyme. PMID- 4041428 TI - Blood group A determinants with mono- and difucosyl type 1 chain in human erythrocyte membranes. AB - Application of a monoclonal antibody defining monofucosyl type 1 chain A (AH21) revealed the presence of a glycolipid having the same thin-layer chromatography mobility as Aa but showing a clear reactivity with AH21. This glycolipid was detectable in Lea-b- erythrocytes but not in Lea+b- or Lea-b+ erythrocytes. Another monoclonal antibody defining difucosyl type 1 chain A (HH3) detected the presence of a glycolipid component reacting with this antibody in Lea-b+ erythrocytes but not in Lea+b- or Lea-b- erythrocytes. The component defined by monoclonal antibody AH21 and that defined by HH3 were isolated and characterized by 1H NMR spectrometry and methylation analysis as having the structures (Formula: see text) The 1H NMR spectra of these glycolipid antigens were characterized by resonances for anomeric protons that are identical with those of glycolipids with type 1 chain previously isolated but distinctively different from those of type 2 chain analogues. Resonances reflecting ceramide composition are characteristic for these antigens from human erythrocytes and are distinguishable from those of the same antigen from other sources. PMID- 4041429 TI - A small hydrophobic domain that localizes human erythrocyte acetylcholinesterase in liposomal membranes is cleaved by papain digestion. AB - A small hydrophobic domain in isolated human erythrocyte acetylcholinesterase is responsible for the interaction of this enzyme with detergent micelles and the aggregation of the enzyme on removal of detergent. Papain has been shown to cleave this hydrophobic domain and to generate a fully active hydrophilic enzyme that shows no tendency to interact with detergents or to aggregate [Dutta Choudhury, T.A., & Rosenberry, T.L. (1984) J. Biol. Chem. 259, 5653-5660]. We report here that the intact enzyme could be reconstituted into phospholipid liposomes while the papain-disaggregated enzyme showed no capacity for reconstitution. More than 80% of the enzyme reconstituted into small liposomes could be released by papain digestion as the hydrophilic form. Papain was less effective in releasing the enzyme from large liposomes that were probably multilamellar. In a novel application of affinity chromatography on acridinium resin, enzyme reconstituted into small liposomes in the presence of excess phospholipid was purified to a level of 1 enzyme molecule per 4000 phospholipid molecules, a ratio expected if each enzyme molecule was associated with a small, unilamellar liposome. Subunits in the hydrophilic enzyme form released from reconstituted liposomes by papain digestion showed a mass decrease of about 2 kilodaltons relative to the intact subunits according to acrylamide gel electrophoresis in sodium dodecyl sulfate, a difference similar to that observed previously following papain digestion of the soluble enzyme aggregates. The data were consistent with the hypothesis that the same hydrophobic domain in the enzyme is responsible for the interaction of the enzyme with detergent micelles, the aggregation of the enzyme in the absence of detergent, and the incorporation of the enzyme into reconstituted phospholipid membranes. PMID- 4041430 TI - Parameters affecting low-pH-mediated fusion of liposomes with the plasma membrane of cells infected with influenza virus. AB - Unilamellar liposomes can be fused at low pH with the plasma membrane of cells that express the hemagglutinin glycoprotein of influenza virus on their surface [van Meer, G., & Simons, K. (1983) J. Cell Biol. 97, 1365-1374]. Here, we have resolved this fusion process into two kinetically distinct steps. The first and more rapid step converts the bound liposome to a form that can no longer be released by neuraminidase. The second step is the actual membrane fusion as measured by the loss of resonance energy transfer between two liposomal fluorescent phospholipids, N-(7-nitro-2,1,3-benzoxadiazol-4 yl)dioleoylphosphatidylethanolami ne (N-NBD-PE) and N-(lissamine rhodamine B sulfonyl)dioleoylphosphatidylethanolamine (N-Rh-PE). In contrast to the first step, the rate of the second one was highly dependent on the liposomal lipid composition and the cell type used. The replacement of 50% of the phosphatidylcholine (PC) in egg PC-cholesterol liposomes by unsaturated phosphatidylethanolamine (PE) species increased the rate of fusion at least 2 fold. Of the PE-containing liposomes that were associated with Madin-Darby canine kidney (MDCK) cells after 30 s of fusion, 80% had actually fused with the plasma membrane. Fringe pattern fluorescence photobleaching experiments showed that after fusion a fraction of the cell-associated N-Rh-PE diffused laterally in the plasma membrane. Without fusion, the N-Rh-PE was completely immobile. Under optimal conditions, the mobile fractions were 65% on MDCK cells and 78% on baby hamster kidney cells. The mobility was acquired simultaneously with the dilution of the fluorescent phospholipids as measured from the loss of resonance energy transfer. The mobile fraction of N-Rh-PE on the cell surface can therefore be used as a second independent measure of actual membrane fusion. Finally, we observed that upon fusion up to 80% of the nonexchangeable liposome markers cholesterol [14C]oleate and glycerol tri[14C]oleate became accessible to cellular hydrolases. The results showed that this hydrolysis assay can also be used to monitor the second step of the fusion process. PMID- 4041431 TI - "Asymmetric" opening reaction mechanism of Z-DNA base pairs: a hydrogen exchange study. AB - With the tritium-Sephadex method, the hydrogen-exchange kinetics of the five NH protons of guanine and cytosine residues in Z-form poly(dG-dC) X poly (dG-dC) were measured as a function of temperature and catalyst concentration. Over the measured temperature range from 0 to 34 degrees C, two classes of protons with constant amplitudes are found. The three protons of the fast class, which were assigned to the guanine amino and imino protons, have an exchange half-time in the minute time range (at 20 degrees C the half-time is 2.5 min) and an activation energy of 18 kcal mol-1. Since these two types of protons exchange at the same rate in spite of their grossly different pK values, the exchange of these protons must be limited by the same nucleic acid conformational change. The two cytosine amino protons of the slow class are especially slow with exchange half-times in the hour time range (at 20 degrees C the exchange half-time is 1 h) and the activation energy is 20 kcal mol-1. The exchange of these two protons is not limited by some nucleic acid conformational change as shown by the marked exchange acceleration of these protons upon addition of 0.2 M imidazole. In addition, we have also reexamined the hydrogen-deuterium exchange kinetics of the amino protons of guanosine cyclic 2',3'-monophosphate by a spectral difference method using a stopped-flow spectrophotometer. The measured kinetic process is monophasic with a rate constant of 3 s-1 at 20 degrees C, which is in the same range as the predicted rate constant of the guanine amino protons.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4041432 TI - Synthesis of d(GC) and d(CG) octamers containing alternating phosphorothioate linkages: effect of the phosphorothioate group on the B-Z transition. AB - The synthesis of four oligonucleotides containing alternating phosphorothioate groups, (Rp)-and (Sp)-d[G(p(S)CpG)3p(S)C] and (Rp)- and (Sp)-d[C(p(S)GpC)p(S)G], by the phosphite approach is described. Silica gel to which 2'(3')-O acetyluridine and 5'-succinyl groups were bound served as support for oligomer synthesis. The syntheses were carried out by dimer addition with presynthesized diastereomerically pure dinucleoside phosphorothioates as building blocks. The products were characterized by 31P NMR, nuclease P1 digestion, and oxidation to the corresponding all-phosphate-containing oligomers. The ability of each oligomer to adopt the Z conformation under high-salt conditions was screened for by circular dichroism spectroscopy. Both (Rp)-d[G(p(S)CpG)3p(S)C] and (Sp) d[C(p(S)GpC)3p(S)G] are capable of forming Z-type structures at high NaCl concentrations. In the case of (Rp)-d[G(p(S)CpG)3p(S)C] where a phosphorothioate of the Rp configuration occurs 5' to a deoxycytidine residue, the B----Z transition is potentiated in comparison to the unmodified oligomer. (Sp) d[G(p(S)CpG)3p(S)C] and (Rp)-d[C(p(S)GpC)3p(S)G] retain the B conformation even at high NaCl concentration. PMID- 4041433 TI - Photoaffinity labeling of the tetrabenazine binding sites of bovine chromaffin granule membranes. AB - An azido derivative of tetrabenazine, a specific inhibitor of the monoamine carrier of chromaffin granule membranes, has been synthesized. In the dark, this compound, 3H-labeled N-(3-isobutyl-9,10-dimethoxy-1,2,3,4,6,7-hexahydro-11bH benzo [a]quinolizin-2-yl)-4-[(4-azido-2-nitrophenyl)amino]butanamide+ ++ ([3H]TBA), bound reversibly to purified chromaffin granule membranes. Centrifugation through SP-Sephadex columns was used to separate bound and free [3H]TBA. This technique gave low levels of nonspecific binding and allowed recovery of [3H]TBA-membrane complexes. Scatchard analysis of the data indicated one class of sites with an equilibrium dissociation constant KD of 50 nM and a density of sites of 40-50 pmol/mg of protein, consistent with reported densities of reserpine and dihydrotetrabenazine binding sites. Competition experiments showed that TBA and tetrabenazine bound to the same site. Irradiation at 435 nm of [3H]TBA-membrane mixtures induced some irreversible binding of the probe to membranes. After irreversible binding of TBA, the number of dihydrotetrabenazine binding sites was decreased, indicating that the probe was covalently bound to the monoamine carrier. [3H]TBA-membrane complexes isolated by centrifugation through SP-Sephadex columns were irradiated, and their radioactivity was analyzed by electrophoresis on sodium dodecyl sulfate/polyacrylamide gels. A polypeptide with a molecular weight of 70 000 was labeled. This polypeptide was different from dopamine beta-hydroxylase, and it was not adsorbed on concanavalin A Sepharose. It is proposed that the monoamine carrier of chromaffin granule membrane has an oligomeric structure, involving a 45K subunit [Gabizon, R., Yetinson, T., & Schuldiner, S. (1982) J. Biol. Chem. 257, 15145] and a 70K subunit. PMID- 4041434 TI - Location of oligo(uridylic acid) sequences within messenger ribonucleic acid molecules of HeLa cells. AB - A significant fraction of the polyadenylated mRNAs of HeLa cells contain an oligo(uridylic acid) [oligo(U)] sequence of 15-30 nucleotides. Several different experimental approaches were used to determine if these oligo(U)'s occupied similar sites within all mRNAs. In one approach, poly(adenylic acid)-containing mRNAs [poly(A+) mRNAs] averaging 2800 nucleotides in length were reduced to an average size of 500 nucleotides by controlled alkaline hydrolysis. Over 20% of the oligo(U)-containing fragments isolated from the hydrolysate retained a poly(A) sequence, showing that oligo(U)'s were not exclusively located near 5' ends of mRNA although 20% were apparently close to 3' ends. To confirm these observations, oligo(U)-containing mRNA [oligo(U+) mRNA] was exposed to the 3' exonucleolytic activity of polynucleotide phosphorylase to produce fragments containing the 5' regions of mRNA. Each of a set of fragments of decreasing length generated by increased times of exposure of the mRNAs to the enzyme was found to have about the same oligo(U) content, including the shortest that averaged 550 nucleotides. These data not only eliminated an exclusive location for oligo(U) in either 3' or 5' ends of mRNA but also suggested that oligo(U)'s might be close to the 5' ends of some mRNAs. To verify this last observation, periodate-oxidized poly(A+) mRNA was labeled at the 5' caps and at 3'-adenosine residues by sodium [3H]borohydride reduction before it was nicked 3-5 times with alkali to produce 5' and 3' end-labeled pieces that could be separated with oligo(thymidylic acid)-cellulose.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4041435 TI - Sequence content of oligo(uridylic acid)-containing messenger ribonucleic acid from HeLa cells. AB - Oligo(uridylic acid)-containing [oligo(U+)] RNA was isolated from poly(adenylic acid)-containing [poly(A+)] mRNA from HeLa cells by using either formaldehyde pretreatment or poly(A) removal, both of which resulted in increased accessibility of oligo(U)-rich sequences to a poly(A)-agarose affinity column. In this report, we compared the sequence content of oligo(U+) RNA with that of molecules lacking oligo(U) [oligo(U-) RNA] by their relative hybridization to cDNA reverse-transcribed from poly(A+) mRNA and by comparison of their in vitro translation products synthesized in a rabbit reticulocyte lysate. Formaldehyde modified poly(A+) RNA, treated to remove the formol adjuncts, was inactive as a template for in vitro protein synthesis; consequently, only depolyadenylated RNA, which retains its translatability, could be used in the translation studies. The hybridization kinetic experiments revealed that oligo(U+) RNA contained most of the sequence information present in oligo(U-) RNA but at a reduced level (ca. 25%), the majority of the oligo(U+) RNA sequences being poorly represented in the cDNA. This result was supported by one- and two-dimensional gel analysis of their in vitro translation products which showed that oligo(U+) RNA, although less effective as a template for translation than oligo(U-) RNA, coded for proteins, the most abundant of which were encoded by rare messages not highly represented in oligo(U-) RNA or the total poly(A+) RNA. Although some minor products were synthesized by both oligo(U+) and oligo(U-) RNA, at least 33 proteins were unique to or highly enriched in the pattern of products directed by oligo(U+) RNA.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4041436 TI - Motion of myosin cross-bridges in skeletal muscle fibers studied by time-resolved fluorescence anisotropy decay. AB - The time-resolved fluorescence polarization anisotropy signal has been measured from fluorescent-labeled myosin cross-bridges in single glycerinated muscle fibers in the relaxed and rigor states. In one experimental configuration, the polarization of the excitation light and the fiber axis are aligned, and the anisotropy is sensitive to rotational motions of the probes about axes other than the fiber axis. The rotational correlation times are approximately 1000 ns for relaxed fibers and greater than 7000 ns for rigor fibers. In another experimental configuration, the excitation light polarization is perpendicular to the fiber axis, and its propagation vector has a component parallel to the fiber axis so that the anisotropy is sensitive to probe rotational motion about different axes, including the fiber axis. In this configuration, the rotational correlation times are approximately 300 ns for both relaxed and rigor fibers. The theory of rotational diffusion in a potential described in a related paper [Burghardt, T.P. (1985) Biophys. J. (in press)] is applied to the relaxed fiber data. PMID- 4041437 TI - Structure and polymorphism of 1,2-dioleoyl-3-acyl-sn-glycerols. Three- and six layered structures. AB - Triacylglycerols, which usually contain at least one unsaturated fatty acid, are the most important forms of stored biological lipids in teleosts, mammals, and most plants. Since the physical properties of such mixed-chain triacylglycerols are poorly understood, a systematic study of such compounds has been initiated. Stereospecific 1,2-dioleoyl-3-acyl-sn-glycerols were synthesized with even carbon saturated fatty acyl chains of 14-24 carbons in length. Their polymorphic behavior was examined by differential scanning calorimetry and X-ray powder diffraction. The thermal behavior revealed from one to four major polymorphic transitions depending upon saturated chain length. Plots of enthalpy of fusion and entropy vs. carbon number for melting of the most stable polymorph were linear throughout the series with slopes of 1.0 kcal/mol per carbon atom and 2.6 cal/(mol K) per carbon atom, respectively. These slopes indicate that the saturated chains are packed in a well-ordered tightly packed lattice. When the compounds were rapidly cooled to 5 degrees C, X-ray powder diffraction revealed strong beta' (ca. 3.8 and 4.2 A) reflections and weak beta (ca. 4.6 A) reflections. The beta subcell reflections intensified when the compounds were heated to within 5 degrees C of the melting temperature of the highest melting polymorph. Evidence of an alpha phase was not seen on 30-min X-ray exposures for any of the compounds. In the proposed packing arrangement the saturated and unsaturated chains are segregated into layers. The stable form of all compounds exhibits a triple layer packing mode in which a bilayer of oleoyl chains is segregated from an interdigitated layer of saturated chains.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4041438 TI - Purification of the calmodulin-sensitive adenylate cyclase from bovine cerebral cortex. AB - A calmodulin-sensitive adenylate cyclase was purified 3000-fold from bovine cerebral cortex using DEAE-Sephacel, calmodulin-Sepharose, and two heptanediamine Sepharose column steps. The purified enzyme activity was stimulated by calmodulin, forskolin, 5'-guanylyl imidodiphosphate, and NaF. The molecular weight of the protein component was estimated as 328 000 with a smaller form of Mr 153 000 obtained in the presence of Mn2+. The most highly purified preparations contained major polypeptides of 150 000, 47 000, and 35 000 daltons on sodium dodecyl sulfate (SDS) gels. Photoaffinity labeling of the preparation with azido[125I]iodocalmodulin gave one product of 170 000 daltons on SDS gels. It is proposed that the catalytic subunit of the calmodulin-sensitive enzyme is 150 000 +/- 10 000 daltons and that the enzyme exists as a complex of one catalytic subunit and the stimulatory guanyl nucleotide regulatory complex. These data are consistent with the previous report that the catalytic subunit of this enzyme has a molecular weight of 150 000 +/- 10 000 [Andreasen, T.J., Heideman, W., Rosenberg, G.B., & Storm, D.R. (1983) Biochemistry 22,2757]. PMID- 4041439 TI - Effects of detergent on substrate binding and spin state of purified liver microsomal cytochrome P-450LM2 from phenobarbital-treated rabbits. AB - Spectral changes accompanying the binding of the nonionic detergent n-octyl beta D-glucopyranoside (n-octyl glucoside) to cytochrome P-450LM2 purified from liver microsomes of phenobarbital-treated rabbits have been compared to changes in catalytic activity obtained in a reconstituted system consisting of various levels of detergent, P-450LM2, and NADPH-cytochrome P-450 reductase. In the absence of substrate and reductase, addition of n-octyl glucoside to 2-3 mM resulted in a difference spectrum (detergent-bound minus detergent-free cytochrome) characterized by a small maximum at 390 nm and a minimum at 410 nm, suggestive of a slight stabilization of the high-spin (S = 5/2) state of the cytochrome. As the detergent concentration was increased to 4-8 mM (corresponding to maximal activity and pentameric or hexameric P-450), a new peak appeared at 427 nm while the minimum remained at 410 nm. Between 10 and 30 mM n-octyl glucoside (conditions which produced catalytically inactive and monomeric P-450) the minimum in the difference spectrum shifted to 390 nm and the maximum to 425 nm, characteristic of a shift in spin equilibrium toward low-spin (S = 1/2) cytochrome. At low and high detergent concentrations, substrate [d-benzphetamine with n-octyl glucoside or cyclohexane with the zwitterionic detergent 3-[(3 cholamidopropyl)dimethylammonio]-1-propanesulfonate (CHAPS)] was bound to P 450LM2 with formation of high-spin P-450, although the increase in high-spin cytochrome was less at high detergent levels than at low. The affinity of P-450 for substrate decreased by 2-3-fold at high detergent.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4041440 TI - Aged human erythrocytes exhibit increased anion exchange. AB - Young and old erythrocytes show different rate constants of anion exchange as measured by 35SO4(2-) efflux at 37 degrees C. Results indicate that the rate constant for 35SO4(2-) efflux (SO2-4-Cl- exchange) from old cells is approximately 20% greater than from young less dense cells. The cell water volume of older cells is also decreased. Based on these results and previously reported decreases of cell membrane area in aged cells we conclude that anion exchange (35SO4(2-)) is increased in older, more dense human erythrocytes. PMID- 4041441 TI - Anion transport in red blood cells and arginine-specific reagents. Interaction between the substrate-binding site and the binding site of arginine-specific reagents. AB - Phenylglyoxal is found to be a potent inhibitor of sulfate equilibrium exchange across the red blood cell membrane at both pH 7.4 and 8.0. The inactivation exhibits pseudo-first-order kinetics with a reaction order close to one at both pH 7.4 and 8. The rate constant of inactivation at 37 degrees C was found to be 0.12 min-1 at pH 7.4 and 0.19 min-1 at pH 8.0. Saturation kinetics are observed if the pseudo-first order rate constant of inhibition is measured as a function of phenylglyoxal concentration. Sulfate ions as well as chloride ions markedly decrease the rate of inactivation by phenylglyoxal at pH 7.4, suggesting that the modification occurs at or near to the binding site for chloride and sulfate. The decrease of the rate of inactivation produced at pH 8.0 by chloride ions is much higher than that produced by sulfate ions. Kinetic analysis of the protection experiments showed that the loaded transport site is unable to react with phenylglyoxal. From the data it is concluded that the modified amino acid(s) residues, presumably arginine, is (are) important for the binding of the substrate anion. PMID- 4041442 TI - X-ray diffraction demonstrates that phosphatidyldiacylglycerol and phosphatidylcholesterol are not lamellar above the main transition temperature. AB - X-ray diffraction was used to investigate the lattice structure of aqueous dispersions of two phosphatidyldiacylglycerols and of a phosphatidylcholesterol above and below the chain melting transition temperature. Previously, Noggle et al. (Biochim. Biophys. Acta (1982) 691, 240-248) had investigated these lipids and had concluded on the basis of electron microscopy that the lipids were in a lamellar state above the transition temperature. However, they found the 31P-NMR signals were not characteristic of lamellar phases. It was, therefore, concluded that these lipids were yielding unexpected 31P-NMR spectra. The present X-ray results demonstrate that, in fact, the lipids are not in a lamellar state above the transition temperature and that the 31P-NMR and X-ray data are not necessarily in disagreement. Characteristics of the phases both above and below the chain melt temperature are discussed. PMID- 4041443 TI - Solute-induced acceleration of transbilayer movement and its implications on models of blood-brain barrier. AB - Hexylglycerol accelerates the transbilayer (flip-flop) movement of phospholipids, lysophospholipids and peptides. For example, lysophosphatidylcholine added to dimyristoylphosphatidylcholine vesicles activates the action of pig pancreatic phospholipase A2 (Jain and DeHaas (1983) Biochim. Biophys. Acta 736, 157-162) This activating effect is dissipated slowly after mixing, and no activation is observed when the lysophospholipid molecules are equally distributed on both sides of the bilayer. The half time for transbilayer movement of lysophosphatidylcholine is about 7 h, and it is accelerated over 100-fold in the presence of n-hexylglycerol, as well as by a variety of other amphipathic solutes including n-alkanols, ketamine, and flufenamic acid. Hexylglycerol also accelerates the rate of transbilayer movement of an amphipathic hexapeptide bocLALALW, as well as of the phosphatidylcholine molecules in erythrocyte membrane. These effects are observed without any change in the gross bilayer organization as judged by 31P-NMR. Biophysical significance of such solute induced acceleration of transbilayer movement of amphipathic solutes is discussed to account for the effect of alkylglycerols on blood brain barrier. PMID- 4041444 TI - The use of cobalt ions as a collisional quencher to probe surface charge and stability of fluorescently labeled bilayer vesicles. AB - Co2+ quenched the fluorescence of the lipid probes NBD-phosphatidylethanolamine (NBD-PE) and lissamine-rhodamine phosphatidylethanolamine (N-Rh-PE) incorporated into lipid vesicles, according to a collisional quenching mechanism in agreement with the Stern-Vollmer law. The quenching coefficient (Q) for NBD-PE, incorporated into uncharged phosphatidylcholine (PC) vesicles was 13.8 M-1. This value was equal to the quenching coefficient of water-soluble NBD-taurine in aqueous solution, indicating that Co2+ was readily accessible to the outer surface of PC vesicles. In phosphatidylserine-phosphatidylethanolamine (PS-PE) (1:1) vesicles, quenching was also proportional to Co2+ concentration but Q was 114 mM-1, some 8000-fold smaller. Using the Gouy-Chapman-Stern model we demonstrated that the surface density of Co2+ bound to lipid was linear with Co2+ concentration in the medium up to 7%. Co2+-associated phospholipid would in turn quench NBD-PE or N-Rh-PE by collisional quenching with lateral diffusion. We investigated the ability of Co2+ to permeate PS-PE (1:1) vesicles. Co2+ quenched fluorophores on the outer surface of large unilamellar vesicles, formed by reverse-phase evaporation. In small unilamellar vesicles Co2+ quenched probes on both outer and inner surfaces, indicating rapid permeation of the ions into the vesicles. Using stopped-flow rapid mixing, we measured the rate of influx of Co2+, and correcting for surface potential using the Gouy-Chapman-Stern model, we calculated a permeability coefficient of 10(-12) cm/s for Co2+ concentrations below 300 microM. Above this concentration, there was a very steep rise in the permeability coefficient, indicating that binding of Co2+ induces defects in the bilayer of these vesicles. This may be related to the ability of the vesicles to undergo membrane fusion. A method for calculating the membrane surface potential from Co2+ quenching data is presented. PMID- 4041445 TI - Effects of long-chain cis-unsaturated fatty acids and their alcohol analogs on aggregation of bovine platelets and their relation with membrane fluidity change. AB - The effects of long-chain cis-unsaturated fatty acids with different alkyl chain lengths and different numbers of double bonds on aggregation of bovine platelets and membrane fluidity were investigated. All the cis-unsaturated fatty acids tested inhibited aggregation and at the same time increased membrane fluidity in accordance with their inhibitory effects. The saturated fatty acids and trans unsaturated fatty acid tested for comparison had much lower or no effects on aggregation and membrane fluidity. The inhibitory effects of mono cis-unsaturated fatty acids increased with increase of their alkyl chain length. cis-Unsaturated fatty acids with two or more double bonds had more inhibitory effects than mono unsaturated fatty acids. The position of the double bonds had less influence than the number of double bonds. We also examined the effects of cis-unsaturated fatty acids on membrane fluidity with diphenylhexatriene and anthroyloxy derivatives of fatty acids as probes and observed increased fluidity to be considerable in the membrane. The alcohol analogs of cis-unsaturated fatty acids also inhibited aggregation and increased membrane perturbation. These results suggest that the inhibition of platelet aggregation by cis-unsaturated compounds is due to perturbation of the lipid layer. PMID- 4041446 TI - Volatile anesthetics cause conformational changes of bacteriorhodopsin in purple membrane. AB - We examined the effects of volatile anesthetics on the structure of the bacteriorhodopsin in the purple membrane by measurements of the absorption spectrum and the visible circular dichroism (CD) spectrum and assay of the retinal composition. As the concentrations of halothane, enflurane and methoxyflurane were increased, the absorption at 560 nm decreased but that at 480 nm increased with an isosbestic point around 510 nm. These anesthetic-induced spectroscopic changes were reversible. The CD spectrum showed the biphasic pattern with a positive and a negative band. As the concentration of halothane was increased from 4 mM to 8mM, the negative band reversibly diminished more drastically than the positive band, and at 8 mM of halothane the positive band shifted to around 480 nm. These results show that halothane disturbed the exciton coupling among bacteriorhodopsin molecules. The retinal isomer composition was analyzed using high performance liquid chromatography. The ratio of 13-cis- to all-trans-retinal was 47:53, 34:66 and 19:81 at control, 7.4 mM and 14.9 mM enflurane, respectively. After elimination of enflurane, the ratio returned to the control value. These findings indicate that volatile anesthetic directly affect a bacteriorhodopsin in the purple membrane and induce conformational changes in it. PMID- 4041447 TI - Regional differences in the lipid composition and fluidity of rat colonic brush border membranes. AB - The lipid composition and fluidity of brush-border membranes prepared from rat proximal and distal colonocytes were determined. Fluidity, as assessed by steady state fluorescence polarization techniques using the fluorophores 1,6-diphenyl 1,3,5-hexatriene, DL-2(9-anthroyl)stearic acid and DL-12(9-anthroyl)stearic acid, was decreased in distal compared to proximal plasma membranes. This pattern was similar to that previously described for both antipodal plasma membranes in rat enterocytes of the small intestine. The decrease in fluidity of the distal as compared to the proximal membranes resulted from an increase in cholesterol content, cholesterol/phospholipid molar ratio and degree of saturation of the fatty acid residues in the distal membranes. The specific activities of total alkaline phosphatase and cysteine-sensitive alkaline phosphatase, enzymes previously shown to be functionally dependent on the physical state of the colonic brush-border membrane's lipid, were also significantly lower in distal as compared to proximal clonic plasma membranes. These studies, therefore, demonstrate that differences in the lipid fluidity, lipid composition and certain enzymatic activities exist in brush-border membranes prepared from rat proximal and distal colonocytes. The regional variation in rat colonic luminal membrane lipid fluidity and composition may, at least partially, be responsible for differences in these enzymatic activities as well as in sodium and water absorption along the length of this organ. PMID- 4041448 TI - Membrane retrieval in the guinea pig neurohypophysis: biochemical characterization of a retrieval structure. AB - [3H]Choline and [35S]methionine injected into the guinea pig hypothalamus in vivo were incorporated into the lipids and proteins, respectively, of secretory vesicles transported to the neural lobe. Prolonged in vivo stimulation of hormone secretion by dehydration decreased the [3H]choline content of secretory vesicles, with a concomitant increase in the [3H]choline content of a membrane fraction isolated on sucrose gradients. After stimulation of neural lobes in vitro in the presence of horseradish peroxidase, this extracellular fluid marker was found in the same membrane fraction. SDS electrophoresis of membrane proteins radiolabelled by [35S]methionine in vivo demonstrated that this fraction contained at least one major protein also present in the secretory vesicle membrane. These results suggest that we have isolated a membrane fraction containing the structure(s) involve in membrane retrieval in the neurohypophysis. PMID- 4041449 TI - Estimation of the location of natural alpha-tocopherol in lipid bilayers by 13C NMR spectroscopy. AB - Natural, 2R,4R',8R'-alpha-tocopherol (vitamin E), labelled selectively with 13C in the methyl group at position 5, was incorporated into unilamellar vesicles of egg phosphatidylcholine. The vesicles are impermeable to the shift reagent Pr3+ and, in the presence of this reagent, separate 13C resonances due to labelled alpha-tocopherol in the outer and inner monolayers could be observed with relative intensities, 2:1. Subsequent addition of the relaxation reagent Gd2+ causes broadening and greatly shortened spin-lattice relaxation times for the resonance due to alpha-tocopherol in the outer monolayer only. These data confirm that alpha-tocopherol is located in both halves of the bilayers with its more hydrophilic chroman moiety very near the lipid-water interface, and indicate that the methyl group at position 5 of the alpha-tocopherol in the inner monolayer must be at least 40 A from the aqueous interface of the outer monolayer. PMID- 4041450 TI - Transport competence of plasma membrane vesicles from cultured human fibroblasts. AB - We obtained plasma membranes from cultured human skin fibroblasts. The preparation was enriched 10-fold with about 40 percent yield. There was minimal contamination with other cell membranes. Various observations indicated vesicular conformation of a portion of the plasma membranes, notably by electron microscopy and from the effect of osmotic pressure on the distribution of solutes between mass and medium at equilibrium. Other studies indicated that these fibroblast plasma membrane vesicles retained mediated transport processes for a variety of substrates. The evidence included: stereospecific and temperature-dependent uptake of glucose; dependence of L-alanine uptake on sodium ion and an inward directed transmembrane Na+ gradient; stimulation of L-alanine uptake, with overshoot, by enhancement of the interior-negative transmembrane potential; concentration dependent uptake of methotrexate with apparent competitive inhibition by folinic acid; stimulation of L-lysine uptake by trans-L-arginine. These findings indicate that human fibroblast plasma membrane vesicles could be used to study membrane transport processes and, perhaps, expression of mutant genes that cause inborn errors of transport. PMID- 4041451 TI - Effects of adriamycin on lipid polymorphism in cardiolipin-containing model and mitochondrial membranes. AB - The effects of the anti-tumor drug adriamycin on lipid polymorphism in cardiolipin-containing model membranes and in isolated inner mitochondrial membranes has been examined by 31P-NMR. Adriamycin binding does not affect the macroscopic structure or local order in the phosphate region of cardiolipin liposomes. In cardiolipin liposomes and in cardiolipin-phosphatidylcholine (1:1) liposomes, the drug inhibits the ability of Ca2+ to induce the hexagonal HII phase. Adriamycin interaction with both dioleoylphosphatidylethanolamine cardiolipin (2:1) and dioleoylphosphatidylethanolamine-phosphatidylserine (1:1) liposomes results in structural phase separation into a liquid-crystalline hexagonal HII phase for the phosphatidylethanolamine and a liquid-crystalline lamellar phase for the negatively charged phospholipid. Combined high-resolution 31P-NMR, electron microscopy and light scattering studies reveal the prominent fusion capacity of adriamycin towards cardiolipin-phosphatidylcholine small unilamellar vesicles. Addition of Ca2+ to total rat liver inner mitochondrial membrane lipids, dispersed in excess buffer, results in hexagonal HII formation for part of the phospholipids. By contrast, the original bilayer structure is completely conserved when the above experiment is performed in the presence of adriamycin. 31P-NMR spectra of isolated inner mitochondrial membranes are indicative of a bilayer organization for the majority of the phospholipids. Approximately 15% of the signal intensity originates from phospholipids which experience isotropic motion. Adriamycin addition almost completely eliminates the latter spectral component. In the absence of adriamycin, Ca2+ addition greatly increases the percentage of the phospholipids giving rise to an isotropic signal possibly indicating the formation of non-lamellar lipid structures. Adriamycin which specifically binds to cardiolipin (K. Nicolay et al. (1984) Biochim. Biophys. Acta 778, 359-371) completely blocks the Ca2+-induced structural reorganization of the lipids in this membrane. PMID- 4041452 TI - Solubilization and reconstitution of the renal phosphate transporter. AB - Proteins from brush-border membrane vesicles of rabbit kidney cortex were solubilized with 1% octylglucoside (protein to detergent ratio, 1:4 (w/w). The solubilized proteins (80.2 +/- 2.3% of the original brush-border proteins, n = 10, mean +/- S.E.) were reconstituted into artificial lipid vesicles or liposomes prepared from purified egg yolk phosphatidylcholine (80%) and cholesterol (20%). Transport of Pi into the proteoliposomes was measured by rapid filtration in the presence of a Na+ or a K+ gradient (out greater than in). In the presence of a Na+ gradient, the uptake of Pi was significantly faster than in the presence of a K+ gradient. Na+ dependency of Pi uptake was not observed when the liposomes were reconstituted with proteins extracted from brush-border membrane vesicles which had been previously treated with papain, a procedure that destroys Pi transport activity. Measurement of Pi uptake in media containing increasing amounts of sucrose indicated that Pi was transported into an intravesicular (osmotically sensitive) space, although about 70% of the Pi uptake appeared to be the result of adsorption or binding of Pi. However, this binding of Pi was not dependent upon the presence of Na+. Both Na+-dependent transport and the Na+-independent binding of Pi were inhibited by arsenate. The initial Na+-dependent Pi transport rate in control liposomes of 0.354 nmol Pi/mg protein per min was reduced to 0.108 and 0 nmol Pi/mg protein per min in the presence of 1 and 10 mM arsenate, respectively. Future studies on reconstitution of Pi transport systems must analyze and correct for the binding of Pi by the lipids used in the formation of the proteoliposomes. PMID- 4041453 TI - Na+-independent dehydro-L-ascorbic acid uptake in renal brush-border membrane vesicles. AB - A membrane preparation enriched in the brush-border component of the plasma membrane was isolated from rat renal superficial cortex by a divalent cation precipitation procedure. Uptake of dehydro-L-ascorbic acid, the oxidized form of L-ascorbic acid, by the brush-border membrane vesicles was studied. The uptake mechanism was found to be sodium-independent and insensitive to the trans membrane electrical potential difference. Uptake was saturable and subject to cis inhibition. Concentrative uptake was demonstrated only under conditions of trans stimulation by structural analogs. The results suggest a mechanism of facilitated diffusion for the uptake of dehydro-L-ascorbic acid in renal brush-border membranes. PMID- 4041454 TI - The topology of the major band 4.5 protein component of the human erythrocyte membrane: characterization of reactive cysteine residues. AB - A preparation of band 4.5 protein of the red cell membrane, containing largely the sugar transporter, was labelled with the sulfhydryl reagent N-ethyl [14C]maleimide. In preparations denatured with sodium dodecyl sulfate (SDS), all five sulfhydryl groups present in the peptide, Mr 45 000 to 60 000, react with the alkylating agent within 20 min at 37 degrees C. If the peptide is reconstituted in lipid vesicles and cleaved with trypsin before extraction and denaturation with SDS, three sulfhydryl groups are found in a 30 kDa fragment and two in a 19 kDa fragment. In 'native' reconstituted protein only three groups react, even after two hours of exposure, two in the 30 kDa fragment and one in the 19 kDa fragment. Thus, one sulfhydryl group is cryptic, inaccessible to N ethylmaleimide in each fragment. In intact cells, the single reactive group of the 19 kDa fragment can be protected against reaction with N-ethylmaleimide by the impermeant sulfhydryl reagent, p-chloromercuribenzene sulfonate (PCMBS). It is, therefore, considered to be exposed on the outer face of the membrane. The two reactive groups of the 30 kDa fragment are not protected by PCMBS and are, therefore, not considered to be exposed to the outside medium. Cytochalasin B, a competitive inhibitor of sugar transport affords temporary protection of the exofacial group of the 19 kDa against reaction with N-ethylmaleimide, and affords longer term protection of one of the reactive groups of the 30 kDa fragment. These findings allow conclusions about the topology of the sugar transport protein in the bilayer. Both proteolytic fragments must cross the bilayer. One of three reactive sulfhydryl groups is exofacial and two may be cytoplasmic. The two cryptic groups may be located within the bilayer. PMID- 4041455 TI - The interaction of calcium with gangliosides in bilayer membranes. AB - We studied the binding of calcium to bilayer membranes formed from mixtures of phosphatidylcholine and mono-, di-, or trisialoganglioside by measuring its effect on the electrophoretic mobility of multilamellar vesicles and the conductance of planar bilayers. In 0.001 M monovalent salt solutions the surface potential of the membranes is large and micromolar concentrations of calcium have a significant effect on the mobility and conductance. In 0.1 M monovalent salt solutions the surface potential is small and millimolar concentrations of calcium are required to affect these parameters. The strong apparent binding of calcium we observed at low ionic strength could be due to the nonspecific accumulation of calcium in the electrical diffuse double layer. To distinguish between this nonspecific effect and binding of calcium to the membrane, we substituted dimethonium for calcium. Dimethonium is a divalent cation that screens negative charges but does not bind to lipids. We also examined the effect of replacing phosphatidylcholine by monoolein: calcium binds to phosphatidylcholine but not to monoolein. We describe our electrophoretic mobility results by combining the Poisson-Boltzmann and Navier-Stokes equations with the Langmuir adsorption isotherm. We conclude that calcium binds weakly to gangliosides with an intrinsic association constant of less than 100 M-1, which is similar to the association constant of calcium with phospholipids. PMID- 4041456 TI - Survival of rabbit and horse erythrocytes in vivo after changing the fatty acyl composition of their phosphatidylcholine. AB - The phospholipid composition and the distribution of phospholipids over the two leaflets of the membrane have been investigated for rabbit and horse erythrocyte membranes. Phosphatidylcholine (PC) comprises 39.4% and 41.3% of the total phospholipid complement of the rabbit and horse erythrocytes, respectively. In both membranes the distribution of this phospholipid is asymmetric: 70% of the PC is present in the outer layer of the rabbit membrane and 60% in that of the horse. The major species of this phospholipid class are the (1-palmitoyl-2 oleoyl)- and the (1-palmitoyl-2-linoleoyl)PC. The disaturated species, (1,2 dipalmitoyl)PC, is present in limited amounts only. Partial replacement of the native PC from intact erythrocytes was accomplished with a purified PC specific transfer protein from bovine liver. Replacement of the native PC species with (1 palmitoyl-2-oleoyl)PC up to 40% of the total PC complement had no effect on the osmotic fragility, the shape and the in vivo survival time of both erythrocyte species. Replacement of the native PC in both rabbit and horse erythrocytes with (1,2-dipalmitoyl)PC up to 20% gave rise to an increased osmotic fragility, a shape change from discocytic to echinocytic and a significant reduction in survival time measured after reinjection of the modified cells. At 30% replacement with (1,2-dipalmitoyl)PC the resulting spheroechinocytes appeared to be cleared from the circulation within 24 h after reinjection. The conclusion can be drawn that the repair mechanisms which may exist in vivo are insufficient to cope with the drastic changes in properties of the erythrocyte membrane which are induced by replacing more than 15% of the native PC by the dipalmitoyl species. PMID- 4041457 TI - Presence of a potential-sensitive Na+ transport across renal brush-border membrane vesicles from rats of the Milan hypertensive strain. AB - Sodium transport was measured in brush-border membrane vesicles prepared from kidney cortex of the Milan hypertensive strain (MHS) rats and the corresponding normotensive controls. In the presence of an outwardly directed proton gradient, 22Na was transiently accumulated in the vesicles. When a transmembrane electrical potential was imposed across membrane vesicles, both the accumulation ratio and the initial uptake were increased, indicating the presence of an electrogenic pathway for sodium in these membranes. The potential-dependent sodium uptake was significantly higher in MHS rats. Kinetic analysis give simple Michaelis Menten curves in the presence and in the absence of a membrane potential. In both conditions Jmax was significantly increased in MHS rats, whereas Km was the same for the two rat strains. Sodium uptake was inhibited by amiloride at concentrations that inhibit Na+-H+ exchange. The presence of the higher, potential-sensitive, sodium uptake in MHS is in agreement with studies on renal physiology which support the hypothesis that an increase in tubular sodium reabsorption may be the primary cause for the development of hypertension in this rat strain. PMID- 4041458 TI - Evidence for a lactate transport system in the sarcolemmal membrane of the perfused rabbit heart: kinetics of unidirectional influx, carrier specificity and effects of glucagon. AB - The kinetics and specificity of L-lactate transport into cardiac muscle were studied during a single transit through the isolated perfused rabbit heart using a rapid (15 s) paired-tracer dilution technique. Kinetic experiments revealed that lactate influx was highly stereospecific and saturable with an apparent Kt = 19 +/- 6 mM and a Vmax = 8.4 +/- 1.5 mumol/min per g (mean +/- S.E., n = 14 hearts). At high perfusate concentrations (10 mM), the inhibitors alpha-cyano-4 hydroxycinnamate (Ki = 7.3 mM), pyruvate (Ki = 6.5 mM), acetate (Ki = 19.4 mM) and chloroacetate (Ki = 28 mM) reduced L-lactate influx, and Ki values were estimated assuming a purely competitive interaction of the inhibitors with the monocarboxylate carrier. The monocarboxylic acids [14C]pyruvate and [3H]acetate were themselves transported, and sarcolemmal uptakes of respectively 38 +/- 1% and 70 +/- 8% were measured relative to D-mannitol. Perfusion of hearts for 10-30 min with 0.15 or 1.5 microM glucagon increased myocardial lactate production and simultaneously inhibited tracer uptake of lactate, pyruvate and acetate. It is concluded that a stereospecific lactate transporter exhibiting an affinity for other substituted monocarboxylic acids is operative in the sarcolemmal plasma membrane of the rabbit myocardium. PMID- 4041459 TI - Effect of a phenyl group in quaternary ammonium compounds on thiamine uptake in isolated rat hepatocytes. AB - The inhibitory effect of a phenyl group in quaternary ammonium compounds on thiamine uptake in isolated rat hepatocytes was investigated. The phenyltrimethylammonium ion was a more potent inhibitor than the tetramethylammonium ion, while the dibenzyldimethylammonium ion was the most potent inhibitor of thiamine uptake among those compounds examined. A kinetic study showed that this compound was a competitive inhibitor. The cetyltrimethylammonium ion was a less effective inhibitor than the benzyltrimethylammonium ion, and the palmitoylcholine ion was a weak inhibitor. These results indicate that the lipophilicity of a quaternary ammonium compound is not always correlated with its affinity for thiamine-carrier binding, but the presence of a phenyl group plays a significant role in affinity. The inhibitory effect of the series of (CH3)3N+ (CH2)nC6H5 (n = 0-6) compounds on thiamine uptake in isolated rat hepatocytes was studied. The maximal inhibitory activity occurred at n = 5. These results suggest that the phenyl group in a quaternary ammonium compound has a specific interaction with the thiamine-binding site in rat liver plasma membrane. PMID- 4041460 TI - Regulation of amino acid transport system L by amino acid availability in CHO-K1 cells. A special role for leucine. AB - Starvation of CHO-K1 cells for leucine leads to a 3-4-fold increase in transport system L activity, without modification of transport through systems A and ASC. The concentration of leucine must be below 10 microM before the enhancement of transport can be clearly seen. To achieve low concentrations of leucine such as 10 microM, extensive dialysis of fetal calf serum was required. The enhancement of transport was completed after 12-24 h of starvation and was fully reversed within 1 h of re-feeding with leucine. Starvation for isoleucine, valine or phenylalanine also produced an increase in system L transport activity, but the effect was only one half of that seen following leucine starvation. PMID- 4041461 TI - The hepatic glucocorticoid domain: evidence for early and late hormone-mediated changes in the synthesis of individual protein gene products. AB - Studies were conducted to determine the extent of rapidly evolving effects of glucocorticoids on the transcriptional activity of individual hepatocyte genes through comparisons of the relative rates of synthesis of the more than 3000 protein gene products that are resolved in giant two-dimensional separatory gels. During the first 20 h in primary culture normal hepatocytes displayed substantial spontaneous changes in over 80 proteins. One effect of an added glucocorticoid, dexamethasone, was to retard or reverse the progression of roughly half of these. However, such long-term hormone treatment also caused 27 inductions and 26 repressions, many of which occurred in proteins that do not change spontaneously. Some of these coincide with the previously reported glucocorticoid domain of hepatoma cells. In contrast to such long-term changes, short-term (4 h) incubation with dexamethasone induced 10 proteins and repressed 6 others. Five of these early hormone inductions and all of the early repressions were maintained or enhanced by 20 h. However, the remaining five early glucocorticoid inductions appeared to be transient, since by 16-20 h the effects were either markedly reduced or absent. These results show the existence of an early glucocorticoid domain, qualitatively different from that seen at later times, which may be more representative of the primary steroid hormone responses. PMID- 4041463 TI - Purification and properties of bovine mammary gland N-acetyl-beta-D glucosaminidase. AB - Two forms of N-acetyl-beta-D-glucosaminidase were purified from bovine mammary gland by DEAE-cellulose chromatography, Sephadex G-200 gel filtration, affinity chromatography on Con A-Sepharose and preparative isoelectric focusing. The two forms, designated A and B on the basis of their binding to DEAE-cellulose at pH 7, were glycoproteins with different molecular weights as determined by gel filtration and sedimentation equilibrium analysis. The A form had a molecular weight of 118 000, while the B form had a molecular weight of 234 000. Both A and B forms of the purified enzyme showed the presence of two distinct subunits, having apparent molecular weights of 55 000 and 25 000 as determined by sodium dodecyl sulphate-electrophoresis. Amino acid composition of the purified forms showed that a high degree of similarity existed between the two forms. However, the B form had slightly higher levels of serine and threonine than the A form. The structure and possible interrelationship of these two forms in the bovine mammary gland are discussed in relation to the structure of N-acetyl-beta-D glucosaminidase from other sources. PMID- 4041462 TI - Ionic effects on the structure of nucleoprotein cores from adenovirus. AB - Nucleoprotein cores, prepared from adenovirus type 5 with a deoxycholate/heat treatment, consist of the viral DNA and two major internal proteins. The core particles exhibit structural characteristics that are highly reproducible and dependent on their ionic environment. In low-ionic-strength buffer, the cores had a sedimentation coefficient of 180 S and appeared in the electron microscope as homogeneous particles with distinct centers from which numerous arms and loops radiated. Condensation of the cores was induced by Mg2+ or Ca2+ over the range 0 to 1 mM. The sedimentation coefficient increased monotonically with divalent cation concentration, reaching a maximum of 405 S in 1 mM Mg2+. A corresponding condensation in the core structure was observed by electron microscopy. Increasing concentrations of NaCl also produced a conformational change in the cores, with an almost linear increase in sedimentation velocity up to 274 S in 0.04 M NaCl. Between 0.05 and 1.0 M NaCl, the cores were insoluble. In 2.0 M NaCl, the cores were again soluble with an s20,w of 228 S. Under all ionic strength conditions in which the cores were soluble, both core proteins remained bound to the DNA. PMID- 4041464 TI - Altered phosphoglycerate kinase from old rat muscle shows no change in primary structure. AB - Phosphoglycerate kinase (ATP:3-phospho-D-glycerate 1-phosphotransferase, EC 2.7.2.3) from young and old rat muscle was purified to homogeneity. After ascertaining that each preparation of the enzyme obtained from the latter indeed possessed altered properties, matched pairs of young and old enzymes were subjected to amino acid analysis and peptide mapping by HPLC. Following S carboxymethylation, the respective young and old enzymes were digested with each of the following three proteinases: trypsin, chymotrypsin and S. aureus V8 proteinase. The corresponding peptides were resolved by reverse-phase HPLC. The peptide patterns obtained from both enzyme forms were identical. Even when the peptides obtained from digestion of phosphoglycerate kinase with S. aureus V8 proteinase were further digested with trypsin, no differences were observed. Comparative amino acid analyses also showed no differences. These results provide direct evidence that there are no changes in the sequence of altered rat muscle phosphoglycerate kinase and support the hypothesis that the differences in properties between the young and old forms of the enzyme result from a conformational modification. PMID- 4041465 TI - Glyceraldehyde-3-phosphate dehydrogenase of rat erythrocytes has no membrane component. AB - In the course of studying mammalian erythrocytes we noted prominent differences in the red cells of the rat. Analysis of ghosts by sodium dodecyl sulfate (SDS) polyacrylamide gel electrophoresis showed that membranes of rat red cells were devoid of band 6 or the glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (D-glyceraldehyde-3-phosphate: NAD+ oxidoreductase (phosphorylating), EC 1.2.1.12). Direct measurements of this enzyme showed that glyceraldehyde-3-phosphate dehydrogenase activity in rat erythrocytes was about 25% of that in human cells; all of the glyceraldehyde-3-phosphate dehydrogenase activity in rat erythrocytes was within the cytoplasm and none was membrane bound; and in the human red cell, about 1/3 of the enzyme activity was within the cytoplasm and 2/3 membrane bound. The release of glyceraldehyde-3-phosphate dehydrogenase from fresh rat erythrocytes immediately following saponin lysis was also determined using the rapid filtration technique recently described. The extrapolated zero-time intercepts of these reactions confirmed that, in the rat erythrocyte, none of the cellular glyceraldehyde-3-phosphate dehydrogenase was membrane bound. Failure of rat glyceraldehyde-3-phosphate dehydrogenase to bind to the membranes of the intact rat erythrocyte seems to be due to cytoplasmic metabolites which interact with the enzyme and render it incapable of binding to the membrane. PMID- 4041466 TI - Vitamin K-dependent carboxylase: the carboxylation of exogenous substrates in different systems. AB - Two types of solid-phase carboxylase, SPC-II and SPC-X, have been prepared from the livers of warfarin-treated cows. Their enzymatic activities were compared with substrate-free carboxylase in microsomes from normal cows and substrate bound carboxylase in microsomes from warfarin-treated cows. A number of exogenous substrates for carboxylase have been purified and tested. We found that large substrates, such as descarboxyprothrombin, are carboxylated only by substrate free carboxylase and not by the substrate-bound enzyme. No differences in apparent Km values between solid-phase carboxylases II and X were observed. PMID- 4041467 TI - Physical properties of chicken erythrocyte HMG-1, HMG-2 and HMG-E. AB - HMG-1, HMG-2 and HMG-E were purified from chicken erythrocyte chromatin without exposure to overt denaturing conditions and subjected to several types of physical measurement. The principal conclusions drawn from the measurements were: none of the proteins has a strong tendency to self-associate, although HMG-1 does weakly self-associate; the frictional properties of HMG-1 and HMG-E (and probably HMG-2) indicate that the proteins deviate significantly from compact, moderately hydrated spheres; and each of the proteins contains approximately 40% helix and little if any beta-pleated sheet. PMID- 4041468 TI - Inactivation of chlorophyllase by negatively charged plant membrane lipids. AB - Chlorophyllide combines spontaneously not only with phosphatidylcholine (PC) liposomes but also with various other (plant) lipids dispersed in an aqueous medium. The lipid-associated chlorophyllide is highly fluorescent and the fluorescence yield is virtually independent of the nature of the lipid. Chlorophyllase (chlorophyll chlorophyllidohydrolase, EC 3.1.1.14) activity assays that are based on the determination of this chlorophyllide fluorescence show that phosphatidylglycerol (PG), and also sulphoquinovosyldiacylglycerol (SQDG), associate with isolated chlorophyllase, thereby inactivating the enzyme in a co operative way. The extent of this inactivation depends on the pH and ionic strength of the reaction medium and can be completely reversed by divalent cations (Mg2+). The inhibition of chlorophyllase effected by free PG liposomes can be counteracted by electrically neutral lipids at relatively high concentration (PC and also chloroplast lipids). Digalactosyldiacylglycerol (DGDG) is not effective in this respect. When PG has been incorporated in PC or DGDG liposomes, its ability to inhibit chlorophyllase activity is reduced. Whereas the remaining chlorophyllase-inactivating effect of PG, incorporated in PC, can still be reversed by Mg2+, this is not found when enzyme inactivation is caused by PG incorporated in DGDG. The results reported here are consistent with those obtained earlier concerning the stabilization of chlorophyllase by PG and PG/galactolipid mixtures (Lambers, J.W.J., Verkleij, A.J. and Terpstra, W. (1984) Biochim. Biophys. Acta 786, 1-8). They are discussed in terms of the regulation of chlorophyllase activity by lipids surrounding the enzyme and by divalent cations. PMID- 4041469 TI - Active forms of chymotrypsin C isolated from autolyzed porcine pancreas glands. AB - Four active forms of chymotrypsin C (C1, C2A, C2B, and C3) were isolated from the autolyzed porcine pancreas glands. Their molecular weights were estimated by SDS polyacrylamide gel electrophoresis to be 29 100 for C1, 26 300 for C2A and C3, and 25 500 for C2B. The kinetic analyses of esterase activity of the enzymes toward Ac-LLeu-OEt and Ac-LPhe-OEt showed that chymotrypsin C1 hydrolyzed the two substrates more efficiently than did chymotrypsin C3. Chymotrypsin C1 consisted of chain A (H-Cys-...-Asn-OH, Mr 886) and chain BC (H-Val-...-Lys-OH, Mr 28 200). Chymotrypsin C3 consisted of the two components of C3L and C3S that could be dissociated in the presence of 2.3% SDS. C3L consisted of the chain A and the chain C (H-Ser-...-Lys-OH, Mr 13 600). C3S was the chain B (H-Val-...-Lys-OH, Mr 11 800). These kinetic and chemical analyses show that chymotrypsins C1 and C3 correspond to chymotrypsin A delta and A alpha, respectively. PMID- 4041470 TI - Activation of lecithin: cholesterol acyltransferase by apolipoproteins E-2, E-3, and A-IV isolated from human plasma. AB - Apolipoprotein A-IV, apolipoprotein E-2 and apolipoprotein E-3 were individually incorporated into defined phosphatidylcholine/cholesterol liposomes for study of lecithin:cholesterol acyltransferase activation. Enzyme activities obtained with these liposomes were compared with that from liposomes containing purified apolipoprotein A-I. Apolipoprotein A-IV, apolipoprotein E-2, and apolipoprotein E 3 all activated lecithin:cholesterol acyltransferase. With purified enzyme and with egg yolk phosphatidylcholine as the acyl donor, maximal activation was obtained at a concentration of approximately 0.5 nmol for apolipoprotein A-IV and 0.4 nmol for the apolipoprotein E isoforms. Apolipoprotein A-IV was approximately 25% as efficient as apolipoprotein A-I for the activation of purified enzyme; apolipoprotein E-2 was 40% as efficient, and apolipoprotein E-3, 30%. Similar activation results were obtained using plasma as the enzyme source. Analysis of the plasma of patients with absence of apolipoprotein A-I or with only trace amounts of apolipoprotein A-I exhibited a reduced rate of cholesterol esterification and lecithin:cholesterol acyltransferase activity that was proportional to the reduced level of the enzyme's mass. These results indicate that apolipoprotein A-IV and apolipoprotein E may serve as physiological cofactors for the enzyme reaction. PMID- 4041471 TI - Monoclonal antibodies to avian lipoprotein lipase. Purification of the enzyme by immunoaffinity chromatography. AB - Three monoclonal antibodies to avian lipoprotein lipase have been isolated by fusing spleen cells from immunized BALB/c mice with myeloma P3X-63 Ag 8. The antibodies were detected by their ability to bind immobilized lipoprotein lipase in enzyme-linked immunosorbent assay (ELISA) and by immunoprecipitation of purified enzyme in the presence of second (rabbit anti-mouse) antibodies. Two of these antibodies, CAL1-7 and CAL1-11, inhibited catalytic activity, whereas with CAL1-2 interaction with lipoprotein lipase could be demonstrated only in ELISA and in Western blot assays following denaturation of the enzyme with sodium dodecyl sulfate. An immunoadsorbent column was prepared by coupling immunopurified CAL1-11 to Sepharose-4B. When acetone powder extracts of adipose tissue were applied on the column, 70% of the catalytic activity bound to the matrix. Effective elution was achieved with 1.8 M NaCl, 40% glycerol, 5% acetone, 20 mM Chaps (3[(3-cholamidopropyl)dimethylammonio]propanesulfonate), 0.5 mM EDTA, 1 mM phosphate (pH 6.5). After concentration of the active fractions on a heparin Sepharose 4B column, the purified enzyme was obtained with an overall recovery of 25%. Sodium dodecyl sulfate polyacrylamide gel electrophoresis demonstrates that the preparation is homogeneous with a major band at Mr 60900. Thus, avian adipose lipoprotein lipase has been purified by a one-step immunoaffinity followed by a concentrating step on heparin-Sepharose 4B. PMID- 4041473 TI - The time-course of lipid biosynthesis in horse skin. AB - To observe the time-course of formation of sebaceous lipids in the horse, skin was pulse-labelled in vivo by intradermal injection of [1-14C]acetate and the injection sites were harvested at intervals for up to 12 days by skin punch biopsy. The distribution of radioactivity among the major neutral lipid classes and the phospholipids from these biopsies showed that, soon after pulse labelling, the phospholipids were highly labelled followed by a long-term decrease in radioactivity. Over the same period, the low initial labelling of the dominant component, the equolides (giant ring omega-lactones, C32-C36), was followed by a long-term increase in radioactivity. This suggests a post-pulse transferance of radioactivity from the phospholipids to the equolides, presumably in the fatty acids. Of the phospholipid fatty acids from horse dermis, including sebaceous glands, 33% were found to contain iso-branched structures unique to horse sebaceous lipids. Of the iso-branched fatty acids, 40% were delta 9-18:1 and delta 9- and delta 11-20:1 acids, which are structurally appropriate to be precursors for the monounsaturated equolides. These findings strengthen the hypothesis that the sebaceous phospholipids of horse skin serve as long-term lipid intermediates in the biosynthesis of the equolides during sebaceous cell development. PMID- 4041472 TI - Macrophage interaction with very-low-density lipoproteins results in triacylglycerol-enriched smooth muscle cells. AB - Macrophage-conditioned medium containing very-low-density lipoproteins (VLDL) and its effects on smooth muscle cell triacylglycerol metabolism was investigated. Macrophages exposed to VLDL from normolipemic rats accumulated high levels of intracellular triacylglycerol, while similarly treated smooth muscle cells showed only slight changes. Medium, initially composed of VLDL and albumin, contained substantial levels of free fatty acids after exposure to macrophages. In the presence of albumin, the loss of VLDL triacylglycerol from the medium and the appearance of medium free fatty acids was consistent with a precursor-product relationship. The extent of medium fatty acid accumulation was dependent on the length of time of incubation with macrophages and was proportional to the concentration of VLDL and albumin added to the culture dish. This macrophage conditioned medium, when given to smooth muscle cells, promoted a 6-12-fold increase in smooth muscle cell triacylglycerol levels over that produced by fresh VLDL and albumin. Similar increases in cell triacylglycerol levels could be produced using fresh medium approximating the oleate concentration and the fatty acid to albumin molar ratios found in macrophage-conditioned medium. In macrophage-conditioned medium with VLDL but without albumin, little free fatty acid was found. Other factors produced by macrophages did not seem to affect the metabolism of VLDL by smooth muscle cells since, in the absence of albumin, media with VLDL caused comparable responses in smooth muscle cell triacylglycerol accumulation whether or not the medium was previously exposed to macrophages. Thus, the minor changes in triacylglycerol content in smooth muscle cells promoted by medium containing VLDL and albumin were substantially enhanced by a prior exposure of the medium to macrophages, primarily due to the free fatty acids present in the macrophage-conditioned medium. PMID- 4041474 TI - Secretion of phospholipase A1 by bone marrow-derived macrophages. AB - Bone marrow-derived macrophages contain phospholipase activity of the A1 and A2 types, active at acid or neutral pH and with different specificities for the fatty acid to be liberated. In contrast to this variety, only one single phospholipase could be detected in extracellular fluids of these cells. Surprisingly, this phospholipase was of the A1 type and active at about pH 8. It exhibited a restricted substrate specificity in that, of the various substrates tested, only phosphatidylcholine containing palmitic acid in position 2 was degraded. This total restriction was not detected with phosphatidylethanolamine substrates. In addition to phospholipase A1, extracellular fluids exhibited lipase activity. A modulation of enzyme secretion could not be achieved by lymphokines or phorbol esters. However, release could be blocked by treating cells with cycloheximide (5 micrograms/ml) or tunicamycin (0.5 micrograms/ml). Phospholipase A1 was also released by thioglycollate-induced peritoneal macrophages. PMID- 4041475 TI - The availability of different sources of cholesterol for bile acid synthesis by cultured chick embryo hepatocytes. AB - The availability of different sources of cholesterol for bile acid synthesis by cultured chick embryo hepatocytes was studied. Mevalonolactone was taken up by the cells and converted to cholesterol, cholesterol ester and tauroconjugates of bile acids. The addition of mevalonolactone had little effect on the conversion of endogenous cholesterol to taurocholic acid; however, taurochenodeoxycholic acid synthesis was stimulated. 25-30% of the cholesterol synthesized from mevalonolactone was converted to taurochenodeoxycholic, taurocholic and two so far unidentified bile acids. All bile acids were secreted into the incubation medium. When cholesterol was added as mixed liposomes with phosphatidylcholine, it was taken up by the cells and converted to bile acids. At low concentrations of liposomes, the greater part of the cholesterol which was taken up by the cells was converted to bile acids. At higher concentrations, considerable amounts of cholesterol and cholesterol ester accumulated inside the cells. When mevalonolactone and cholesterol liposomes was added together, both substrates were used simultaneously for bile acids synthesis. HDL cholesterol was the best substrate tested, yielding large amounts of two, so-far, unidentified bile acids (possibly allo-bile acids) and smaller amounts of taurocholic and taurochenodeoxycholic acid. Addition of HDL suppressed the conversion of endogenous cholesterol to taurocholic acid; taurochenodeoxycholic acid synthesis, however, was stimulated. PMID- 4041476 TI - The sites of degradation of purified rat low density lipoprotein and high density lipoprotein in the rat. AB - Low density lipoprotein and high density lipoprotein were isolated from rat serum by sequential ultracentrifugation in the density intervals 1.025-1.050 g/ml and 1.125-1.21 g/ml, respectively. The isolated lipoproteins were radioiodinated using ICl. Low density lipoprotein was further purified by concanavalin A affinity chromatography and concentrated by ultracentrifugation. 95% of the purified low density lipoprotein radioactivity was precipitable by tetramethylurea, while only 4% was associated with lipids. The radioiodinated high density lipoprotein was incubated for 1 h at 4 degrees C with unlabelled very low density lipoprotein, followed by reisolation by sequential ultracentrifugation. Only 3% of the radioactivity was associated with lipids and 90% was present on apolipoprotein A-I. The serum decay curves of labelled and subsequently purified rat low and high density lipoprotein, measured over a period of 28 h, clearly exhibited more than one component, in contrast to the monoexponential decay curves of iodinated human low density lipoprotein. The decay curves were not affected by the methods used to purify the LDL and HDL preparations. The catabolic sites of the labelled rat lipoproteins were analyzed in vivo using leupeptin-treated rats. In vivo treatment of rats with leupeptin did not affect the rate of disappearance from serum of intravenously injected labelled rat low density lipoprotein and high density lipoprotein. Leupeptin dependent accumulation of radioiodine occurred almost exclusively in the liver after intravenous injection of iodinated low density lipoprotein, while both the liver and the kidneys showed leupeptin-dependent accumulation of radioactivity after injection of iodinated high density lipoprotein. PMID- 4041477 TI - The presence of 5 alpha-sitostanol in the serum of a patient with phytosterolemia, and its biosynthesis from plant steroids in rats with bile fistula. AB - The presence of 5 alpha-sitostanol (24-ethyl-5 alpha-cholestan-3 beta-ol) in serum of a patient with the rare genetic disease phytosterolemia was confirmed. This study aimed at clarifying the pathway(s) for the formation of 5 alpha sitostanol, by use of rats with bile fistula. 5 alpha-Sitostanol was formed only slowly from sitosterol, but readily from 24-ethyl-4-cholesten-3-one. Some conversion was also obtained with 7 alpha-hydroxysitosterol as precursor. In view of the low rate of 7 alpha-hydroxylation of sitosterol, however, a pathway from sitosterol to 5 alpha-sitostanol involving 7 alpha-hydroxysitosterol as intermediate is probably of small physiological importance. Intestinal microorganisms are not essential for the above conversions, since the 5 alpha sitostanol was found in bile from bile fistula rats. 5 alpha-Sitostanol was converted to water soluble metabolites (bile acids) much more slowly than was cholestanol (5 alpha-cholestan-3 beta-ol), and was accumulated serum to a much larger extent. PMID- 4041478 TI - Triacylglycerol increase in plasma very low density lipoproteins in cyclophosphamide-treated rabbit: relationship with cholesteryl ester transfer activity. AB - We have studied the cholesteryl ester transfer between HDL and VLDL in cyclophosphamide-treated rabbits, in order to explain the abnormal cholesteryl ester partition between these two lipoprotein classes. The hypertriglyceridemia caused by treatment with the drug was associated with cholesteryl ester- and triacylglycerol-rich VLDL and with HDL poor in esterified cholesterol but relatively enriched in triacylglycerol. These two lipoprotein classes were characterized by their chemical composition and by gel filtration chromatography. VLDL particles were slightly larger in size, compared with controls. Different transfer combinations were envisaged between these abnormal lipoproteins and control ones. The transfer study involved the plasma fraction of d greater than 1.21 g/ml containing the cholesteryl ester transfer protein (CETP). It appeared that the chemical composition of lipoproteins was responsible for the level of cholesteryl ester transfer between lipoproteins. Actually, when the cholesteryl ester acceptor lipoproteins (VLDL) were enriched in triacylglycerol, the transfer was enhanced. Therefore, the effect of lipolysis on the transfer has also been explored. Lipoprotein lipase seemed to enhance the transfer of cholesteryl ester from HDL to VLDL when these lipoproteins were normal, but an important decline was obtained when triacylglycerol-rich VLDL were lipolyzed. This study defines the relationship between lipoprotein chemical composition and transfer activity of cholesteryl ester from HDL to VLDL. PMID- 4041479 TI - Cholesterol can stimulate secretion of apolipoprotein B by cultured human hepatocytes. AB - During a 5 day cultivation of human hepatocytes in a primary culture the secretion of apolipoprotein B was measured by enzyme-linked immunosorbent assay. Density-gradient ultracentrifugation demonstrated that the majority of the secreted apolipoprotein B was associated with the very-low-density lipoprotein fraction. Exposure of the cells to cholesterol (5-100 micrograms/ml) resulted in a dose-dependent increase in apolipoprotein B secretion rate. PMID- 4041480 TI - Effect of age on the modification of rat plasma lipids by fish and soybean oil diets. AB - The effects of sardine and soybean oils on plasma lipids have been studied in young and aged rats. Plasma cholesterol and bile acids of aged rats fed on a sardine oil diet decreased to a greater degree than those of young rats. Cholesterol, bile acids and phospholipids of the soybean oil diet group decreased only in aged rats. Increases in plasma eicosapentaenoic (sardine) and linoleic (soybean) acid levels of aged rats were observed to be greater than those of young rats. These results indicate that the age enhances the effects of fish and soybean oils on plasma lipids by suppressing their characteristic fatty acid metabolism. PMID- 4041481 TI - Immunochemical studies on biosynthesis of rat plasma angiotensinogen and its regulation by cortisol. AB - Glucocorticosteroid hormones increase the level of rat plasma angiotensinogen by increasing its rate of synthesis. Two forms of plasma angiotensinogen have been purified differing with respect to molecular weight and affinity to concanavalin A. Immunochemical studies using antibodies raised against the separated forms of angiotensinogen revealed cross-reactivity with both antigens. Both antibodies were able to quantitatively precipitate the angiotensinogen activity present in rat serum samples. Cortisol increased the total amount of plasma renin substrate without changing the relative amounts of both angiotensinogen forms. mRNA coding for plasma angiotensinogen was determined by in vitro translation of poly(A) containing RNA and immunochemical analysis of translation products. Angiotensinogen mRNA could be detected in total poly(A)-containing RNA isolated from rat liver, but not in mRNA isolated from brain, although angiotensinogen has been reported to be present in the latter organ. The level of hepatic mRNA coding for plasma angiotensinogen was high in rats treated with cortisol, but not detectable in animals depleted from endogenous glucocorticosteroids by bilateral adrenalectomy. PMID- 4041482 TI - The transformation of chlorophenols by lactoperoxidase. AB - The lactoperoxidase-catalyzed transformations of penta-,2,3,4,6-tetra-, 2,4,6-tri , 2,4-di- and 4-monochlorophenol were followed spectrophotometrically. Apparent stoichiometries of chlorophenol:H2O2 ranged from 1:1 for the tri- and tetrachlorophenol at pH7 to 5:2 for pentachlorophenol at pH 4. The initial velocity (v0) was only slightly influenced by changes in [H2O2] greater then 5 microns. v0 responded to [chlorophenol] according to the empirical expression v0=[lactoperoxidase] . (k1[chlorophenol] + k2[chlorophenol]2). The constant k1 was trichlorophenol, respectively, at pH 7. With the di- and monochlorophenol the solution soon became opaque, and the reaction ceased. The results show that more than one reaction occurs. Some comparisons were also made with horseradish peroxidase A and C. Cetyltrimethylammonium bromide prevented opaqueness, but was shown to be a substrate for lactoperoxidase. Assuming an average concentration of 0.1 microns for H2O2 and pentachlorophenol in man, the metabolic rate becomes 30 ng/h per g of peroxidase-containing tissue, possibly with deposition of the products. PMID- 4041484 TI - The effect of quin2 on chemotaxis by polymorphonuclear leukocytes. AB - Exposure of rabbit polymorphonuclear leukocytes to micromolar concentrations of quin2-AM results in high intracellular concentrations of quin2, which lead to inhibition of chemotaxis. The loading efficiency of polymorphonuclear leukocytes, being the percentage of quin2-AM which is taken up by the cells and transformed intracellularly into quin2, is very high, reaches a maximum after 30 min, is independent of the presence of extracellular Ca2+ and is fairly independent of cell concentration. As a consequence, inhibition of chemotaxis is strongly dependent on experimental conditions: with a low cell density (3 X 10(6)/ml) exposure to 20 microM quin2-AM results in complete inhibition of chemotaxis, whereas the same concentration of quin2-AM is nearly without effect when an 8 fold higher cell concentration is used. Inhibition by quin2 is dependent on extracellular Ca2+; inhibition is more pronounced in the absence of extracellular Ca2+ than in its presence. It is suggested that quin2 inhibits chemotaxis by interference with intracellular Ca2+. PMID- 4041483 TI - Evidence that membrane phospholipids and protein are required for binding of diphtheria toxin in Vero cells. AB - Treatment with phospholipase C strongly protected monkey kidney (Vero) cells against diphtheria toxin and reduced the ability of the cells to bind 125I labelled toxin. Treatment with phospholipase D and with trypsin also protected the cells, although to a lesser extent. Phospholipase A2 had no protective effect. Phospholipase C also protected fetal hamster kidney cells against the toxin. After removal of the enzymes, as well as after treatment of the cells with 4-acetamide 4'-isothiocyanostilbene 2,2'-disulfonic acid, diphtheria toxin binding capability was restored slowly, apparently by a process requiring protein synthesis, since cycloheximide blocked the restoration. The data indicate that both phospholipids and protein are involved in the binding sites for diphtheria toxin. PMID- 4041485 TI - Repair of methylated bases in mammalian cells during adaptive response to alkylating agents. AB - Pretreatment of H4 (rat hepatoma) cells for 48 h with non toxic doses of alkylating agents methylmethane sulfonate, (MMS), N-methyl-N'-nitro-N nitrosoguanidine (MNNG) renders the cells more resistant to the toxic and mutagenic effects of these compounds. This adaptive response seems to reflect improved repair of methylated lesions in cellular DNA. Therefore, we measured the activity of the DNA-glycosylase for N-methylated purines (7-MeGua and 3-MeAd) and the activity of the O6-methylguanine-DNA methyltransferase in control and adapted cells. We show that the adaptive response does not significantly increase the DNA glycosylase activity but involves the induction of methyltransferase molecules. PMID- 4041486 TI - Evolution of replicators playing a strategic game. AB - A mathematical model of replicator evolution is considered. Replicators are words of a formal language specifying a strategy for a parlour game. They replicate with mutations and are selected according to their pay-off against other replicators. PMID- 4041487 TI - A two dimensional model for saccade generation. AB - A model for the generation of oblique saccades is constructed by extending and modifying the one dimensional local feedback model. It is proposed that the visual system stores target location in inertial coordinates, but that the feedback loop which guides saccades works in retinotopic coordinates. To achieve straight trajectories for centripetal and centrifugal saccades in all meridians, a comparator computes motor error as a vector and uses the vectorial error signal to drive two orthogonally-acting burst generators. The generation of straight saccade trajectories when the extraocular muscles are of unequal strengths requires the introduction of a burst-tonic cell input to motor neurons. The model accounts for the results of two-site stimulation of the superior colliculus and frontal eye fields by allowing simultaneous activation of more than one comparator. The postulated existence of multiple comparators suggests that motor error may be computed topographically. PMID- 4041488 TI - A neuro-synaptic model of the auditory masking and unmasking process. AB - A model of bilateral information processing in the auditory system was presented on the basis of the interaction of postsynaptic potentials intra- and inter nuclei in order to analyze the mechanism of binaural unmasking as well as monaural masking. The system was composed of a bilateral pair of auditory nuclei, which were organized in two parallel afferent systems as well as an efferent system. In the model, bilateral inputs were processed in three stages, i.e., the detection of interaural differences by the first afferent system, the equalization of relative neural timing by the efferent system, and the cancellation of specific spectral components by the second afferent system. Assuming the masking process to be forward and backward inhibitions on the auditory memory of signal by the ones of noise, the unmasking process could be explained as a result of disinhibition by the cancellation of bilateral masker inputs. PMID- 4041489 TI - On the mechanisms underlying appearance of responses to movement, directional sensitivity and velocity tuning of the cat's striate cortical neurons. AB - The responses to moving and stationary stimuli of 27 cat's striate cortical units were studied. Two stationary light bars located in different parts of the receptive field were used. The order of presentation and the time-interval between the stimuli varied; so, the presentation of a pair of stationary stimuli was an analogue of a moving stimulus. It was shown that responses occurred in neurons previously unresponsive to stationary stimuli when two stationary stimuli were presented successively in certain order. In the direction-sensitive units an asymmetry of the temporal course of the inhibitory processes was observed. The inhibitory zone located on the side of the preferred direction of movement was characterized by an early inhibitory phase followed by a phase of disinhibition and by a second inhibitory phase. For the inhibitory zone located on the side of the null direction no disinhibitory phase was demonstrated. The significance of the spatial and temporal characteristics of the receptive field for the appearance of responses to movement, the directional sensitivity and the velocity tuning in striate neurons is discussed. PMID- 4041490 TI - Cross-modal identification: effects of contingent changes in the stimulus series. AB - Two computer controlled experiments in an olfactory cross-modal matching task, using two-component odour mixtures matched against bar diagrams, were designed so that stimulus presentation was contingent upon the recent performance of the subject; stimuli that were relatively poorly (in experiment 1) or well (in experiment 2) matched were more frequently presented. Analysis shows that the autoregressive structure of the performance is modified by such contingent presentation and that there is a weak relationship between transmitted information in matching and the time series structure of the matching errors. It is suggested that the process is nonlinear. PMID- 4041491 TI - [Interaction of blood sex steroid-binding globulin-steroid complexes with plasma membranes of human decidual endometrium cells]. AB - Plasma membranes of decidual tissue cells specifically bind the sex steroid binding globulin (SBP) complexes with estrogen (estradiol, estriol, estrone) and with the pharmacological agent danazol but do not interact with the SBP testosterone or SBP-dihydrotestosterone complexes. The selectivity of interaction of the SBP-steroid complexes with decidual tissue cellular membranes provide evidence for the active role of SBP in the realization of steroid effects on the target tissue. PMID- 4041492 TI - [Effect of hyperthermia on the polypeptide composition of the nuclear matrix of the rat liver]. AB - The increase in rat body temperature by 2-3 degrees as a result of overheating (45 degrees C, 22% humidity) over 90 and 120 min is accompanied by changes in the rate of labeled precursors incorporation into rat liver protein fractions. The incorporation of labeled amino acids into liver nuclear matrix proteins within the first 90 min of overheating is somewhat decreased, whereas 120 min thereafter it exceeds by 30% the corresponding values in control animals kept at room temperature. The polypeptide pattern of the nuclear matrix in hyperthermia is characterized by an increased relative content of polypeptide components around Mr 100, 55, 40 and 30 kDa against a decreased level of several polypeptides as compared to the control. PMID- 4041493 TI - [Aggregation of fragmented chromatin associated with the synthesis of products of its treatment with nuclease]. AB - Isolated cell nuclei were incubated with nucleases followed by extraction of chromatin with a low salt buffer. With an increase of nuclear chromatin degradation with DNAse I or micrococcal nuclease, solubilization of deoxyribonucleoprotein (DNP) by a low salt buffer increases, reaching a maximum upon hydrolysis with 2-4% nuclear DNA and then decreases appreciably after extensive treatment with nucleases. Soluble fragmented chromatin aggregates in the course of treatment with DNAase. I. Addition to gel chromatin preparations of exogenous products of nuclease treatment of isolated nuclei leads to its aggregation. Pretreatment of nuclear chromatin with RNAase prevents solubilization of DNP by low ionic strength solutions. Some experimental data obtained with the use of severe nuclease treatment are discussed; for a correct interpretation of these data the aggregation of fragmented chromatin by products of its nuclease degradation should be taken into consideration. PMID- 4041494 TI - [Interaction of blood sex steroid-binding globulin with cell membranes of human decidual tissue]. AB - The interaction of sex steroid-binding globulin (SHBG) from human blood with plasma membranes of human decidual tissue cells (estradiol target tissue) was investigated. It was shown that SHBG complexed with estradiol specifically interacts with these membranes. The dissociation constant (Kdis) for this interaction is (3.5 +/- 2.0) X 10(-12) M. The interaction of the SHBG-estradiol complex with the membranes is characterized by a high selectivity; such serum globulins as albumin, orosomucoid, transferrin, transcortin and the thyroxine binding globulin do not compete with SHBG for the binding sites on the membranes. The SHBG-testosterone complex and SHBG alone do not interact with the membranes either. PMID- 4041495 TI - [Structural characteristics of DNA from the rat liver during inhibition of protein synthesis with cycloheximide]. AB - At cot around 20, the rat liver DNA reassociation curves were obtained 12-48 hours after injection of the animals with sublethal doses of cycloheximide. In total preparations of DNA-24 and DNA-36 at cot 0.02-0.06, the number of fast reassociating sequences was increased, on the average, by 4%. The differences in reassociation rates for individual kinetic fractions are 2.5-3-fold. The total incorporation of the label into DNA-24 preparations is sharply decreased; however, a marked distinction in the incorporation between the fractions in parameter cot was observed. PMID- 4041496 TI - [Structural characteristics of the recognition site of cholinergic ligands of the nicotinic acetylcholine receptor from squid optic ganglia]. AB - The effect of chemical modification on the binding of cholinergic ligands to nicotinic acetylcholine receptor from squid optical ganglion was studied. The existence of two chemically distinct subpopulations of binding sites was postulated. Subpopulation I contains, in all probability, Arg, Tyr and carboxyl groups critical for the binding of both ligands. Subpopulation II differs from the first one in the amino group present instead of Arg. The amino group important for the binding of d-tubocurarine alone was found in both subpopulations. The data obtained allow one to construct a model of nicotinic acetylcholine receptor cholinergic ligand recognition sites. PMID- 4041497 TI - [Induction of microsomal cytochromes in the rat liver after intravenous administration of emulsions of perfluoro-organic compounds]. AB - Intravenous injections of perfluoroorganic emulsions to rats in a dose of 3 ml/kg led to changes in the composition and activity of enzymes of the liver microsomal membrane monooxygenase system. At the peak of induction, i. e., on the 3rd post injection day, the levels of microsomal cytochromes P-450 and b5 increased 2.8- and 1.9-fold, respectively, as compared to the control. Simultaneously, the rate of NADPH oxidation in the microsomes and the rate of hydroxylation of substrates I and II showed an increase. Conversely, the rate of NADPH-dependent peroxidation of microsomal lipids on the 2nd-4th post-injection days reached its minimal values. These injections stimulated the detoxicating function of rat liver as evidenced from the duration of the hexenal sleep of the animals. All the changes in the monooxygenase system parameters were temporary and reached the control level on the 10th-14th days after injection. It was demonstrated that the main component of the perfluoroorganic emulsions, perfluorodecalin, was responsible for the induction of the monooxygenase system enzymes. PMID- 4041498 TI - [Dependence of the properties of dioxane-based scintillation systems on the concentration of the components]. AB - Characteristics of dioxan-based scintillation system have been studied. A composition for scintillation cocktails ensuring an effective homogeneous count of radioactive water samples (0-8% V) at minimum expense of ethyl alcohol has been suggested. PMID- 4041499 TI - Nonmigrating rhythmic activity in the stomach and duodenum of neonates. AB - We studied gastrointestinal motility in 20 infants, using a modified manometric method for neonates, and compared it to that in adults. Changes in the intragastric and intraduodenal pressures were recorded for 3 h after the ingestion of milk. Bands of contractions with the same rhythmicity as phase III activity in adults were frequently recorded. Some of them migrated caudally and were speculated to the equivalent of phase III activity of the interdigestive migrating complex (IMC) in adults. However, others did not migrate and showed some differences from phase III activity of adults and infants in the time of occurrence, duration and amplitude. The characteristic of gastroduodenal motility in infants was the frequent occurrence of these bands of nonmigrating rhythmic concentrations. Our findings indicated the following problems: (1) there are some differences in gastrointestinal motility between infants and adults and further investigations are required for the evaluation of the physiology or pathophysiology of this phenomenon; (2) in infants, many bands of rhythmic contractions of the alimentary tracts can exist without migration. This indicates the possibility that the occurrence of rhythmic contractions and their migration are regulated by different mechanisms. PMID- 4041500 TI - Small intestine transit time and lactose absorption during phototherapy. AB - Diarrhea is often seen during phototherapy in jaundiced infants. Lactose malabsorption and reduced gut transit time (GTT) are some of the proposed explanations. However, the etiology of the diarrhea is still controversial. We investigated GTT and lactose absorption during phototherapy using the H2 breath test. Breath H2 was measured every 10 min for 150 min after feeding of jaundiced infants with and without phototherapy, and in controls. There were 12 newborns in each group. The time of increase of H2 excretion over 10 ppm was taken as the transit time. Lactose malabsorption was estimated by integrating the area under the excess H2 curve. No difference was found in GTT, lactose absorption, peak breath H2 and the time of the peak between phototherapy-treated infants and jaundiced and nonjaundiced infants. The results did not support the presence of lactose malabsorption during phototherapy and the decreased total GTT reported in the literature was not due to shortened small intestinal transit time. PMID- 4041501 TI - Starvation-induced organ hypoplasia in prenatal and postnatal guinea pigs. AB - The severity and permanence of growth retardation was measured in guinea pigs starved for 3 weeks with a 50% ration in late gestation (prenatal), at birth (neonatal), or at weaning. Acute and chronic effects were assessed as body mass, skeletal length, hematology, and the weight, DNA and protein contents of the hearts, the lungs, and the livers of the starved and refed animals. Organ hypoplasia was most pronounced in the prenatally starved group, and was associated with numerous stillbirths. Among survivors, catch-up growth was eventually complete. Prenatal starvation of this species provides a reproducible model of human intrauterine growth retardation, particularly of the pulmonary system. PMID- 4041502 TI - Changes in plasma arginine vasopressin during transition from fetus to newborn following minimal trauma delivery of lambs and goats. AB - Vasopressin in umbilical arterial and venous blood is high at delivery and may be important in the maintenance of arterial pressure and absorption of lung liquid. We used chronically instrumented near-term fetal lambs and goats to investigate the changes in plasma vasopressin that occur during perinatal cardiovascular transition following cesarean section without labor. Plasma arginine vasopressin was more than 5 times greater 15 min following birth than immediately prior to clamping the umbilicus, and it fell progressively over the ensuing 2-5 h to levels not significantly different from before birth. Fifteen min after delivery, neither arterial pressure, blood gases, nor pH appeared to account for the increase. PMID- 4041503 TI - Protection by magnesium of renal calcinosis in furosemide-treated weanling rats with moderate magnesium deficiency. AB - Prolonged treatment of premature infants with the potent diuretic furosemide has resulted in hypercalciuria, sometimes with renal calcinosis and other complications. Furosemide was administered to weanling rats to explore its effect on magnesium and calcium metabolism. The animals were fed purified diets providing 40 mg magnesium/100 g diet or 10 mg magnesium/100 g. Half of each dietary group (40-F or 10-F) received 18 doses of furosemide, 20 mg/kg body weight, intraperitoneally between days 7 and 35, and half received normal saline intraperitoneally (40-O or 10-O). Furosemide had little effect on the magnesium sufficient animals (40-F), but comparison of 10-O and 10-F data showed that it aggravated the magnesium-deficiency syndrome. Comparison of data from 40-F and 10 F animals showed the protective effect of magnesium in preserving calcium homeostasis in furosemide-treated animals: the elevation of calcium values in 10 F rats was greater in plasma (p less than 0.0005), heart (p less than 0.0025), and kidney (p less than 0.0005). Stated another way, furosemide was associated with severely disordered calcium metabolism only in animals fed suboptimal magnesium. Studies exploring the role of magnesium in furosemide-treated infants can be recommended. PMID- 4041504 TI - Autoregulation of cerebral blood flow in the newborn beagle puppy. AB - Regional cerebral blood flow (RCBF) was measured in 17 newborn beagle puppies under conditions of moderate hypotension, normotension, and moderate hypertension. RCBF demonstrated autoregulation over the blood pressure range 35 70 mm Hg. When arterial pressure exceeded 75 mm Hg, RCBF increased significantly for all grey matter structures, 2 of 4 white matter structures, and 2 of 3 germinal matrix structures. The magnitude of the hypertension-induced increase in RCBF was highest for thalamic and mesencephalic nuclei, intermediate in cerebral cortex and other subcortical nuclei, and lowest in white matter. The hypertension induced increase in CBF was low (similar to white matter) in some areas of germinal matrix but higher (similar to midline cerebral cortex) to rostral germinal matrix. The differences in RCBF during hypertension between rostral germinal matrix and cerebral white matter may partially explain the vulnerability of the germinal matrix to hemorrhage. PMID- 4041505 TI - Effect of digitoxin on vaginal epithelial differentiation in the Balb/c mouse. AB - Vaginal epithelial differentiation (VED) in the mouse and the human is the replacement of columnar by squamous epithelium in the vagina. This occurs in humans in late first and second trimesters of pregnancy and in mice after birth. In both diethylstilbestrol (DES) exposure during the process is associated with persistence of columnar epithelium and later reproductive tract tumor. Cardiac glycosides are estrogenic in both species. The concern: could cardiac glycosides produce similar effects to those seen after DES? Digitoxin was administered to Balb/c neonates at increasing doses. VED occurred by 10 days in three low-dose groups. Cardiotoxic mortality precluded study at higher doses. Therefore digitoxin did not affect VED. PMID- 4041506 TI - Placental handling of zinc in the guinea pig. AB - The distribution of zinc between the mother and the fetoplacental unit, and its placental transfer, were studied using stable and isotopic zinc in unanaesthetized pregnant guinea pigs and an in situ perfusion preparation. The concentration of stable zinc in fetal plasma and skeletal muscle was higher than that in the maternal tissues: 2.0 compared with 1.4 micrograms/ml and 84 with 49 ng/mg dry weight, respectively. The placenta and maternal and fetal liver had similar zinc concentrations: 90, 75 and 88 ng/mg dry weight, respectively. The ability of the placenta to concentrate 65Zn, measured 1 h after a single intravenous injection into the unanaesthetized mother, was comparable with that of the maternal liver. Maternal-fetal mass transfer of zinc was directly related to maternal plasma zinc concentrations from 0.7 to 24.1 micrograms/ml (b = 2 ng X min-1 X g-1 X microgram-1, r = 0.92). At physiological plasma levels, the calculated transfer would supply the fetus with 0.12 mg zinc/day, similar to the accretion rate over the last trimester. Placental transfer of zinc was not influenced by the concentration of zinc in the placental perfusate. Extraction of zinc from the perfusate was also slow, and partly by absorption. Maternofetal transfer of zinc was directly related to both uterine and umbilical blood flows. The high concentration of zinc in the syncytium, relative to both maternal and fetal plasma levels, suggests active uptake at the maternal surface, combined with a slow release into the fetus, down a concentration gradient. PMID- 4041507 TI - Carnitine and carnitine transferases in the intestinal mucosa of suckling rats. AB - Carnitine acetyltransferase and palmitoyltransferase activity in the mucosa of the small intestine of rats rises after birth and falls at the time of weaning. The carnitine contents of the mucosa (free, acetyl-, palmitoyl- and total) decrease postnatally, reaching adult levels at the time of weaning. Orally administered 14C-carnitine is only slowly absorbed so that radioactivity is still high in plasma and organs 6 h later, whereas label given subcutaneously disappears from the plasma and tissues more rapidly. The intestinal mucosa also takes up carnitine from 14C-carnitine administered subcutaneously. It is concluded that carnitine plays an important role in the gut of suckling rats. PMID- 4041508 TI - Effects of fasting on glucose turnover rate and metabolite levels in conscious pregnant guinea pigs. AB - The effect of fasting during pregnancy is of particular interest in the guinea pig because of the large fetal mass carried to term. The present studies examined the effect of acute and chronic starvation on maternal glucose turnover in the guinea pig. In the first experiment, 7 near-term pregnant guinea pigs were fasted for 6 h. The maternal glucose concentration and glucose production decreased rapidly, falling to about 65-70% of fed levels at 4 h of starvation. Mothers demonstrated a 2.6-fold elevation in ketoacids after 2, 4 and 6 h starvation. In a second experiment, 5 non-pregnant and 11 near-term pregnant animals were studied in the control period and after 24 h of fasting. The maternal glucose concentration in the control state was independent of fetal mass. The maternal glucose turnover rate in the fed state correlated linearly with fetal mass. After 24 h of fasting, the glucose concentration and glucose turnover rate both decreased, with the magnitude of each decrease proportional to fetal mass. We conclude that, in the pregnant guinea pig, the fetal mass impacts significantly on maternal glucose metabolism in the fed and fasting states. PMID- 4041509 TI - Counting counts. PMID- 4041510 TI - Abnormal cerebrospinal fluid protein indices in schizophrenia. AB - Determinations of albumin and immunoglobulin G (IgG) were performed in paired cerebrospinal fluid (CSF) and serum samples from 24 subjects with schizophrenia. These determinations allowed calculation of two indices, one that is an indicator of integrity of the blood-brain barrier and the other a measure of selective IgG production within the central nervous system (CNS). In comparison with previously determined reference values, 7 of 24 (29%) subjects showed increased blood-brain barrier permeability, and 8 of 24 (33%) demonstrated elevated endogenous CNS IgG production. One of these eight also demonstrated oligoclonal banding on high resolution protein electrophoresis of the CSF. PMID- 4041511 TI - Daily patterns of serotonin uptake in platelets from psychiatric patients and control volunteers. AB - Serotonin (5-HT) uptake into platelets from psychiatric patients and controls was measured in the morning and afternoon. Uptake varied with time of day in both groups studied, resulting in four recognizable patterns. Two patterns occurred in the majority of controls. In contrast, uptake patterns in the psychiatric patients were more variable, with each of the four patterns clearly represented. However, except for the fact that uptake was significantly decreased throughout the day in depressed patients, the patterns were not otherwise linked statistically to clinical condition. In any event, the greater variability of daily 5-HT uptake patterns in patients suggests that psychiatric disorders linked presumably to central nervous system (CNS) dysfunction are in some way reflected by labile platelet 5-HT pharmacokinetics. PMID- 4041512 TI - Use of the polyethylene glycol adduct of L-asparaginase for the treatment of hyperasparaginemia in a schizophrenic patient. AB - A man with hyperasparaginemia, presumably due to chronic deficiency of asparaginase activity, had been schizophrenic and unresponsive to antipsychotic drugs for at least 22 years. He was given repeated injections of bacterial L asparaginase rendered relatively nonimmunogenic by covalent binding to polyethylene glycol (PEG). PEG-asparaginase lowered plasma asparagine concentrations from 4 to 5 SD above normal down to undetectable levels, and eliminated asparagine from the cerebrospinal fluid. Despite biochemical correction lasting at least 55 days, the patient did not improve psychiatrically. Experience limited to this single patient suggests that PEG-asparaginase therapy is relatively innocuous, but does not clarify whether there is an etiological relationship between hyperasparaginemia and psychiatric illness. PMID- 4041513 TI - The effect of nonsedating doses of diazepam on regional cerebral blood flow. AB - Drugs like diazepam induce tranquilization in small doses and sedation in larger quantities. Regional cerebral blood flow (rCBF) was measured before and 5 min after the intravenous administration of nonsedating doses of diazepam or placebo (given on a double-blind basis) to 20 right-handed volunteers. Subjects who received diazepam showed marked right hemispheric rCBF decreases, especially in the frontal lobe, whereas controls did not show significant differences between the two sets of values. None of the subjects became sleepy during the experiment. PMID- 4041514 TI - Normal pressure hydrocephalus and psychiatric patients. PMID- 4041515 TI - Lateralization of visual hallucinations in chronic schizophrenia. PMID- 4041516 TI - Gender effects seen in the cerebral ventricular/brain ratio (VBR). PMID- 4041517 TI - Introversion, attention and the late positive component of event-related potentials. AB - Variation in P3 amplitude across normal individuals under the same experimental conditions has been routinely observed. The possibility that such variation reflects individual differences in the allocation of attention was examined by comparing P3 amplitude in introverts and extraverts, who are thought to differ in the allocation of attention during monotonous tasks. Event-related potentials were recorded while the subjects participated in a lengthy stimulus prediction task. P3 amplitude was determined by principal components analysis and it was found to be significantly larger for the introverts than for the extraverts. This finding is interpreted as evidence that P3 amplitude is sensitive to individual differences in the allocation of attention. PMID- 4041518 TI - Cardiac responses to psychological tasks: impedance cardiographic studies. AB - In a series of studies, cardiac activity, assessed with an impedance cardiograph, was monitored as college students performed either a visual search or pursuit rotor task. Heart rate, systolic time intervals, stroke volume, cardiac output and the Heather (1969) index of contractility were measured before, during and after performance. In the first study, visual search did not affect the participants' (N = 44) level of cardiac output or their length of the pre ejection period. It is likely that the lack of charge in cardiac output resulted from a fall in stroke volume and in the Heather index while the task was performed. Heart rate was most rapid during performance and emerged as the only measure affected by the withdrawal of monetary incentives for failure to solve the visual search problem. In the second study, 40 subjects performed a pursuit rotor task and increases in cardiac output as well as changes in all of the other cardiac measures occurred. The level of task difficulty influenced the extent of heart rate increases and stroke volume decreases during performance. An additional 20 male subjects participated in a third study in which the level of difficulty of the pursuit rotor task was signalled and the order of the levels of difficulty was balanced across trial blocks. Under these conditions, the changes in cardiac activity before, during and after performance were similar to those observed in the first two studies. Heart rate was the only measure sensitive to the level of task difficulty. In general, the findings underscore the sensitivity of heart rate to changes in subtle aspects of psychological situations. To enlist increases in cardiac output and inotropic parameters extensive alterations in behavioral state are required. PMID- 4041519 TI - Transcutaneous partial oxygen tension and skin blood flow monitoring: continuous, noninvasive measures of cardiorespiratory change. AB - Transcutaneous partial oxygen tension (tc pO2) and skin blood flow (via heat clearance) were measured noninvasively in 22 male subjects who performed stress inducing tasks (i.e. hand-grip exercise, cold pressor test, breath holding, hyperventilation and mirror-tracing). An analysis of variance and covariance was conducted for tc pO2, heat clearance, heart rate, respiration rate, finger pulse volume and systolic/diastolic blood pressure. Results indicate that tc pO2 can depict phasic cardiorespiratory challenge. Heat clearance proved to be less sensitive to the demand conditions used here. An analysis of covariance revealed a negative correlation between tc pO2 and blood pressure and respiration rate, as well as a positive correlation between tc pO2 and heat clearance. This suggests that phasic changes in tc pO2 are induced by both peripheral vasomotor activity and changes in arterial pO2. PMID- 4041520 TI - Pheromone-induced reproductive inhibition in young female Peromyscus leucopus. AB - Soiled bedding and urine from adult female white-footed mice (Peromyscus leucopus) were tested for their capacity to inhibit reproduction of young females. Test animals were given either physical or airborne contact with soiled bedding from adult females, adult female urine, clean bedding, or water from 21 to 150 days of age. Results indicate that reproductive inhibition is due to an airborne pheromone emitted by the adult females as a component of their urine. In the second experiment, young female mice were exposed to an adult female for 0, 1, 3, 6, 12, 18, or 24 h/day from 21 to 150 days of age. Results from this experiment show that exposure to adult females of as little as 3 h/day was sufficient to cause reproductive inhibition to occur. This phenomenon has important implications in terms of both female-female reproductive competition and socially mediated population regulation. PMID- 4041521 TI - Sexual maturation in male Belding's ground squirrels: influence of body weight. AB - The relation between body weight and sexual maturation was examined in a hibernator, Belding's ground squirrel, by manipulating the availability of food to weaned juvenile males. Following body weight manipulation in the summer, testicular growth, serum testosterone, and spermatogenesis were monitored during the subsequent year, which included 7 mo when males were in the coldroom (ca. 8 degrees C), followed by 5 mo in the laboratory (ca. 20 degrees C). Juveniles (less than 1 yr old) maintained on a restricted diet entered the coldroom at normal body weights for their age class in nature and had immature gonads throughout the year, which is characteristic of this group in the field. In contrast, juveniles given abundant food during the summer entered the coldroom at body weights typical for free-living yearlings and exhibited mature gonads shortly after males were removed from the cold (high relative testis weights, high serum testosterone levels, and all stages of spermatogenesis). The high level of gonadal activity in overfed males was confined to a period of a few weeks in the spring, which coincided with the time when mating occurs in nature. The ability of male Belding's ground squirrels to accumulate body weight prior to hibernation seems important to sexual maturation in this seasonally breeding rodent. PMID- 4041522 TI - Changes in patterns of luteinizing hormone secretion before and after the first ovulation in the postpartum mare. AB - To determine whether luteinizing hormone (LH) secretion during the first estrous cycle postpartum is characterized by pulsatile release, circulating LH concentrations were measured in 8 postpartum mares, 4 of which had been treated with 150 mg progesterone and 10 mg estradiol daily for 20 days after foaling to delay ovulation. Blood samples were collected every 15 min for 8 h on 4 occasions: 3 times during the follicular phase (Days 2-4, 5-7, and 8-11 after either foaling or end of steroid treatment), and once during the luteal phase (Days 5-8 after ovulation). Ovulation occurred in 4 mares 13.2 +/- 0.6 days postpartum and in 3 of 4 mares 12.0 +/- 1.1 days post-treatment. Before ovulation, low-amplitude LH pulses (approximately 1 ng/ml) were observed in 3 mares; such LH pulses occurred irregularly (1-2/8 h) and were unrelated to mean circulating LH levels, which gradually increased from less than 1 ng/ml at foaling or end of steroid treatment to maximum levels (12.3 ng/ml) within 48 h after ovulation. In contrast, 1-3 high-amplitude LH pulses (3.7 +/- 0.7 ng/ml) were observed in 6 of 7 mares during an 8-h period of the luteal phase. The results suggest that in postpartum mares LH release is pulsatile during the luteal phase of the estrous cycle, whereas before ovulation LH pulses cannot be readily identified. PMID- 4041523 TI - Seasonal changes in pulsatile luteinizing hormone (LH) secretion in the ewe: relationship of frequency of LH pulses to day length and response to estradiol negative feedback. AB - Seasonal changes in pulsatile luteinizing hormone (LH) secretion in ovariectomized ewes were examined over the course of 2 yr in relation to annual changes in environmental photoperiod, shifts in response to estradiol negative feedback control of LH secretion, and timing of the breeding season. Under natural environmental conditions, the frequency of LH pulses in individual ovariectomized ewes changed gradually and in close association with the annual cycle of day length. As days became shorter in late summer and autumn, LH pulse frequency increased; conversely, as day length increased in late winter and spring, frequency declined. Under artificial conditions in which ovariectomized ewes were exposed to different photoperiods, a similar inverse relationship was observed between day length and LH pulse frequency. The seasonal changes in frequency of LH pulses in ovariectomized ewes, although symmetric with the annual photoperiodic cycle, were not temporally coupled to the dramatic shifts in response to estradiol feedback inhibition of LH secretion at the transitions between breeding season and anestrus. The feedback shifts occurred abruptly and at times when LH pulse frequency in ovariectomized ewes was at, or near, the annual maximum or minimum. The tight coupling between LH pulse frequency and photoperiod leads to the conclusion that there is a photoperiodic drive to the LH pulse-generating system of the ewe. The temporal dissociation between changes in this photoperiodic drive and the seasonal shifts in response to estradiol negative feedback support the hypothesis that the neuroendocrine basis for these two phenomena is not one and the same. PMID- 4041524 TI - Development of hamster circadian rhythms. I. Within-litter synchrony of mother and pup activity rhythms at weaning. AB - The circadian wheel-running activity rhythms of individual hamster pups raised and maintained in constant dim light were measured beginning at 18 days of age. Records of the postweaning free-running activity rhythm were used to determine the phase of a pup's rhythm on the day of weaning and its phase relationship to its mother's rhythm. Although raised in constant light, the rhythms of pups within a litter were approximately synchronous and in phase with their mother's activity rhythm. These results indicate that the circadian oscillator underlying the activity rhythm is functional prior to weaning and is entrained by some as yet unidentified aspect of maternal rhythmicity. Furthermore, the results suggest that even in the absence of external entraining cycles, behavioral rhythms, and perhaps physiologic rhythms as well, of a mother and her offspring are normally synchronized. PMID- 4041525 TI - Prepuberal reproductive defects in neonatal estrogenized male rats. AB - Intact Wistar male rats injected on Day 1 with 500 micrograms of estradiol benzoate or olive oil were decapitated on Days 15 and 22 or maintained until adulthood to analyze the balanopreputial separation. Other oil or estradiol treated rats were orchidectomized on Day 15 and decapitated on Day 22. The neonatal estrogenization produced the following reproductive changes prior to puberty: testis, adrenal, and ventral prostate atrophy; increase in the weights of seminal vesicles and epididymis; decrease in testosterone plasma levels; delayed balanopreputial separation; abolition of luteinizing hormone response to orchidectomy; transient increase in prolactin plasma levels; and blockade in seminal and prostate response to orchidectomy. PMID- 4041526 TI - In vitro fertilization in the rabbit after delayed ovum recovery. AB - Rabbit ovum donors were superovulated with pregnant mare's serum gonadotropin (PMSG) and human chorionic gonadotropin (hCG). Ova were recovered 16-17 h post hCG from oviducts immediately after killing and from excised oviducts held in saline 30 min at 33 degrees or 38 degrees C prior to ovum recovery. In vivo capacitated spermatozoa were used to inseminate both groups of ova. Data revealed a decrease in fertilization rates following a 30-min delay at 38 degrees C in ovum recovery. Thus, 64% (44/69 ova) were fertilized with rapid recovery, whereas 43% (39/90 ova) were fertilized following a 30-min delay. The decrease in fertilization imposed by delay in ovum recovery was apparently overcome when oviduct storage was at 33 degrees C. Under these conditions, 69% of inseminated ova were fertilized. Ova inseminated with in vitro-capacitated sperm showed a similar response to delayed ovum recovery. Embryonic development in culture of ova obtained from mated does was not affected by delay in recovery at 33 degrees or 38 degrees C provided mated does had been injected only with hCG. Ova from mated does receiving both PMSG and hCG were adversely affected by a 38 degrees C delay. The data emphasize the importance of rapid ovum recovery from oviducts and suggest the possibility of altering conditions to overcome damaging effects of delayed recovery. PMID- 4041528 TI - Ontogeny of growth hormone, prolactin, luteinizing hormone, and testosterone secretory patterns in the ram. AB - The ontogenetic changes that occur in secretory patterns of growth hormone (GH), prolactin (Prl), luteinizing hormone (LH), and testosterone (T) in rams maintained in constant photoperiod were examined. Nine ram lambs were moved to individual pens in a controlled environment (12L: 12D cycle; 18-24 degrees C temperature) at 66 days of age. Blood samples were collected via indwelling cannulae at 15-min intervals for an 8-h period at 80, 136, 192, 248, and 304 days of age. Plasma concentrations of GH, Prl, LH, and T were quantitated and parameters of the secretory patterns determined. Mean concentration of GH tended to decline with age, probably because the amplitude of secretory peaks was significantly reduced with age. There were no age-associated changes in basal concentration of GH or incidence of GH peaks. There was an increase in Prl secretion (as estimated by mean concentration) at 136 and after 248 days of age. Significant age-associated changes occurred in all parameters of LH and T secretion. At the younger ages, testosterone concentrations were low and LH concentrations were elevated. At the older ages the relationship was reversed, with LH low and testosterone high. There were no significant correlations between frequency and magnitude of LH and T peaks. The significant correlations present among parameters of LH and T secretion were between basal concentration of LH and overall mean concentration and basal concentration of T. These results suggest that LH may not be the sole tropic stimulator of acute T secretion. PMID- 4041527 TI - Pregnancy in young and aged rats: II. Peripheral serum progesterone concentrations. AB - The concentrations of serum progesterone (P4) were determined in 3- and 11-mo-old female rats throughout pregnancy to determine if the subnormal ovarian formation of P4 from pregnenolone (P5), previously shown in vitro in the older rats, is accompanied by lower concentrations of P4 in the peripheral serum. Beginning on Day 11 of gestation and continuing throughout the remainder of pregnancy, 11-mo old females exhibited a decline in the number of live fetuses and an increase in the number of dead fetuses. Between Days 1 and 8 of gestation, serum P4 concentrations were similar in young and aging females. Between Days 9 and 21 of gestation, serum P4 concentrations in aging rats that maintained pregnancy, or that exhibited fetal loss, were consistently greater than in the young animals. The normal or above-normal concentrations of serum P4, despite the subnormal ovarian formation of P4 demonstrable in vitro in 11-mo-old females during the first half of pregnancy, may reflect an alteration in the peripheral catabolism of P4 or no change in ovarian secretion of P4 in vivo. Despite the changes in ovarian steroidogenesis observed in vitro, pregnancy failure in aging female rats is not related simply to subnormal content of P4 in the peripheral circulation. PMID- 4041529 TI - Relative luteinizing hormone-stimulable adenylyl cyclase of the preovulatory follicle: a predictor of ovulation in the domestic hen. AB - The regulation of the ovulatory cycle of the hen (Gallus domesticus) is an enigma. The hen's ovulatory cycle is approximately 26 h in length. She lays an egg each day at a progressively later time. The hen then skips a day, resets her "clock", and a new sequence is started. We investigated if the ovary regulates the ovulatory cycle. Our biologic endpoint was the measurement of basal and luteinizing hormone (LH)-stimulable adenylyl cyclase (AC) activity in granulosa layers of the largest (F1) and second largest (F2) follicles. F1 and F2 follicles were obtained at lights off on nights before the first (C1; n = 7), second (C2; n = 7), or terminal ovulation (CT; n = 5) or the night before the day when no ovulation was expected (Cskip; n = 6). F1 and F2 follicles removed on C1, C2, CT, and Cskip had been these specific follicles for 32 h, 12 h, 10 h, and 8 h, respectively. Mean basal activity (pmol/min/mg protein) for the follicles was: C1 = 27.2, C2 = 44.1, CT = 60.5, and Cskip = 68.7. No significant differences were found in LH-stimulable AC activities of these F1 follicles. Relative LH (expressed as fold increase over basal) stimulation was significantly correlated (P less than 0.001) with maturity of the F1 follicle (C1 greater than C2 greater than CT greater than Cskip). No differences in AC activity were found for the F2 follicles whether they were C1, C2, CT or Cskip. For the Cskip, relative LH AC activity for the F1 follicle (2.8) was similar to that for the F2 follicle (2.7).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4041530 TI - The development of placental androstenedione and testosterone production and their utilization by the ovary for aromatization to estrogen during rat pregnancy. AB - During rat pregnancy the placenta may provide androgens as a source of precursor for estradiol (E2) formation by the ovary. However, the relative importance of testosterone (T) and delta 4-androstenedione (delta 4 A) for ovarian E2 production is unknown. The present study therefore determined the ability of the rat placenta to convert [3H] pregnenolone (P5) substrate to [3H] delta 4 A and [3H] T, and to [3H] progesterone (P4) in vitro on Days 12, 14, 16 and 18 of gestation. The placental formation of delta 4 A and T was correlated with the uterine vein and peripheral sera concentrations of both androgens, and with their ability to be aromatized to E2 in vitro by the ovary. Placental androgen formation from P5 increased and formation of P4 decreased with advancing gestation, with the formation of delta 4 A being approximately 2- to 4-fold greater (P less than 0.01) than the formation of T on Days 12 to 16 of gestation. The conversion of P5 to delta 4 A increased (P less than 0.001) from 18 +/- 0.9 (mean percent conversion +/- SEM) on Day 12 to 53 +/- 3 and 57 +/- 4 on Days 14 and 16, respectively, then decreased (P less than 0.05) to 42 +/- 2 on Day 18. The uterine vein and peripheral sera concentrations of delta 4 A were 2- and 3 fold greater (P less than 0.05-0.001) than T, respectively, on Days 12 to 16.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4041531 TI - Steroidogenic effect of 17 beta-estradiol on rabbit luteal cells in vitro: estrogen-induced maintenance of progesterone production. AB - Previous studies have established that 17 beta-estradiol is the principal luteotropic hormone in the rabbit. However, a direct effect of 17 beta-estradiol on rabbit luteal cell progesterone production has been difficult to show in vitro. The goal of this study was to develop a system in which the effect of estrogen on luteal cell progesterone production could be studied in vitro. To that end, a dissociated rabbit luteal cell preparation was developed using collagenase and the resultant isolated cells were studied using a perifusion system. Optimization of the cell digest procedure revealed that: inclusion of 2% bovine serum albumin in our optimal dissociation medium increased cell yield; and animals killed by cervical dislocation maintained more stable levels of progesterone during a 7-h perifusion compared to animals killed with barbituate induced euthanasia (euthobarb). When dissociated luteal cells were perifused with medium, stable progesterone output (greater than 80% of initial levels) was observed for 5-6 h, after which medium progesterone concentrations declined. The inclusion of 17 beta-estradiol (10(-8) M) in the perifusion medium maintained progesterone output at control levels for up to 15 h. However, the maintenance of progesterone was not noted until after 5 h of perifusion, suggesting that the effect of estradiol may be time dependent. Thus, this investigation describes a rabbit luteal cell dissociation technique and perifusion system that may be used to examine the mechanism through which estradiol acts to maintain rabbit luteal progesterone production. PMID- 4041532 TI - Steroidogenesis in porcine atretic follicles: loss of aromatase activity in isolated granulosa and theca. AB - To evaluate the mechanisms involved in the reduction of estrogen concentrations in porcine follicular fluid during atresia, nonatretic and atretic follicles ranging from 4 to 7 mm in diameter were selected. Follicular fluid estrogen concentrations were 7-16-fold less in the atretic follicles. Isolated granulosa cells from atretic follicles demonstrated a significant reduction in aromatase activity and in follicle-stimulating hormone (FSH)-induced progesterone production in vitro compared to granulosa cells from nonatretic follicles. Isolated theca from atretic follicles also demonstrated a reduction in estrogen production. However, androgen concentrations were equivalent in the follicular fluid of atretic and nonatretic follicles, and theca from atretic follicles maintained testosterone and androstenedione production in vitro. The loss of thecal aromatase activity with atresia is not secondary to a reduction in FSH responsiveness, since FSH did not increase thecal progesterone production in vitro. Cell degeneration also does not account for the reduction in thecal estrogen production, since both androgen output in vitro and follicular fluid androgen concentrations were maintained. These data thus demonstrate that a mechanism other than reduced FSH responsiveness must account for the selective loss of thecal aromatase activity in this stage of atresia. PMID- 4041533 TI - Light and electron microscopic studies on the localization of steroid-binding protein (SBP) in rabbit spermatozoa. AB - Light (fluorescence) and electron microscopic studies were carried out to localize steroid-binding protein (SBP) in rabbit spermatozoa. Both nonpermeabilized and permeabilized (with Tween 20, saponin, or cold acetone) spermatozoa showed fluorescence following treatment with antirabbit SBP (anti rSBP) and subsequently with rabbit antisheep immunoglobulin G-fluorescein isothiocyanate. While the ejaculated spermatozoa were positive, epididymal sperm were observed to be negative. Although the pattern of localization of rSBP was variable, the occurrence of a negative equatorial region as well as the presence of an intense positive spherical profile ("spot") at the junction of the head and midpiece were notably consistent. The intensity of labeling with the probe, both at light and electron microscopic level, was maximal following permeabilization with cold acetone. A possible role of SBP as a steroid carrier protein across the plasma membrane of the sperm has been suggested. PMID- 4041534 TI - Mouse sperm antigens that participate in fertilization. II. Inhibition of sperm penetration through the zona pellucida using monoclonal antibodies. AB - To dissect the process of mammalian sperm interaction with the egg at a molecular level, we have generated monoclonal antibodies (mAbs) to mature mouse sperm using syngeneic mouse testis as the immunogen. In this paper, we report upon three members of a mAb family, all of which displayed identical immunofluorescence patterns on cauda epididymal mouse sperm. Each of these mAbs, termed M42, M5, and M41, localized to a restricted region of plasma membrane overlying the acrosome. When tested for an effect on the fertilization process in vitro, two of the mAbs, M42 and M5, demonstrated significant inhibition. The inhibitory capacity was dependent upon the presence of the zona pellucida; neither M42 nor M5 was capable of blocking fertilization when zona pellucida-free mouse eggs were used. Identification of the antigens recognized by this group of mAbs was achieved by immunologic detection of sodium dodecyl sulfate-extracted sperm components separated via electrophoresis on 12% sodium dodecyl sulfate-polyacrylamide gels followed by transfer to nitrocellulose. M42, which blocked fertilization, recognized a high molecular weight cluster of bands with Mr of approximately 220,000 to 240,000. M5, which also prevented fertilization, specifically recognized a sperm component with subunit molecular weight of approximately 54,000. M41, which did not interfere with fertilization, did not interact with any high molecular weight components, but recognized components with Mr of approximately 60,000, 35,000, and 21,000. Taken together with the work presented in a companion paper (Saling, Irons, and Waibel, this issue), we have demonstrated that it is possible to describe particular cellular regions of mammalian sperm with respect not only to location and function, but also to the molecules that are candidates for a role in that function. PMID- 4041535 TI - Mouse sperm antigens that participate in fertilization. III. Passive immunization with a single monoclonal antisperm antibody inhibits pregnancy and fertilization in vivo. AB - Passive immunization was used to study the effect of antimouse sperm monoclonal antibodies on fertilization in vivo. The effects of two antibodies were compared in this investigation. One of them, M29, has been shown previously to localize to the equatorial segment of the sperm head and to inhibit mouse fertilization in vitro in a concentration-dependent manner. The second antibody, M2, binds to the same area of the sperm head, and also belongs to the M immunoglobulin class (IgM), but does not affect fertilization in vitro. Superovulated female mice received two antibody injections intraperitoneally (at the times of the pregnant mare's serum gonadotropin and human chorionic gonadotropin injections) at concentrations of 0.5-4.0 mg of IgM or control IgG; animals were mated within 6 12 h of the hCG injection. Fertilization and concomitant establishment of pregnancy were reduced significantly, in a dose-dependent manner, only in those animals immunized with M29 IgM (e.g., 4 mg M29 IgM: 12.6% of 304 eggs fertilized; 4 mg M2 IgM: 96% of 192 eggs fertilized). Intraperitoneal administration of the antibodies did not depress superovulation levels nor oocyte viability. 125I labeled M29 IgM was used to determine the amount of antibody present in the oviductal ampulla at the time of fertilization in passively immunized mice. Luminal M29 IgM was found to be a linear function of the intraperitoneal dose: 0.002-0.003% of the injected dose was present in the oviductal lumen 14-16 h post hCG.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4041536 TI - Spatial modulation of water ordering in lecithin bilayers. Evidence for a ripple ripple phase transition. AB - Intense motional averaging effects on the 2H nuclear magnetic resonance (NMR) spectrum of 2H2O that occur in aqueous dispersions of dimyristoyl-sn-glycero-3 phosphocholine (Myr2-PtdCho) are explained by a spatial modulation in the orientational order of the water induced by ripplelike structures. The ratio of the amplitude to the periodic length of the ripples, A/lambda, at a molar ratio of water/Myr2-PtdCho of 9.5:1, is measured by 2H NMR and found to be consistent with x-ray measurements of this ratio in the P beta phase of dipalmitoyl-sn glycero-3-phosphocholine (Pam2-PtdCho) bilayers. The sensitivity of 2H NMR allows us to report the presence of two distinct ripple phases mediated with a discontinuous change in the value of A/lambda. This result suggests that the two ripple structures observed for several phospholipid systems in excess water by freeze-fracture electron microscopy may be associated with two different phases instead of the same phase as previously assumed. PMID- 4041537 TI - Macro- and micro-stabilities of the kringle 4 domain from plasminogen. The effect of ligand binding. AB - 1H-NMR spectra of kringle 4 from human plasminogen have been recorded over wide pH* and temperature ranges, both in the presence and in the absence of p benzylaminesulfonic acid (BASA). Several resonances exhibit chemical shift differences between kringle folded and unfolded forms which are sufficiently well resolved to allow for a determination of equilibrium Van't Hoff enthalpies and entropies for unfolding. The interaction with BASA shifts the kringle unfolding temperature from approximately 335 degrees K to approximately 343 degrees K. The pH* range of stability is also wider for the complex than for the free kringle: in the acidic range the pH* of half-unfolding, pHu*, is decreased from 2.8 for the unligated polypeptide to approximately 2.0 in the presence of BASA, while in the basic range pHu*, shifts from approximately 10.8 to 11.5. However, in contrast with what is observed at acidic pH*, unfolding at basic pH* leads to irreversible denaturation and exhibits a sharp, order-disorder transition both in the presence and in the absence of ligand. The structural stabilization conferred by the ligand is accompanied by a drastic reduction of the average rate of 1H-2H exchange in 2H2O under conditions that preclude a major cooperative unfolding. Thus, macro- and micro-stabilities of kringle domains appear to be highly correlated. PMID- 4041538 TI - Linear impedance studies of voltage-dependent conductances in tissue cultured chick heart cells. AB - Plateau and pacemaker currents from tissue cultured clusters of embryonic chick heart cells were studied in the time domain, using voltage-clamp steps, and in the frequency domain, using a wide-band noise input superimposed on a steady holding voltage. In the presence of tetrodotoxin to block the sodium channel, a depolarizing voltage step into the plateau range elicited: (a) a rapid (approximately equal to 2 ms) activation of the slow inward current; (b) a subsequent slower (approximately equal to 25 ms) decline in the slow inward current; and (c) activation of a very slow (5 to 10 s) outward current. Impedance studies in this voltage range could clearly resolve two voltage-dependent processes, which appeared to correspond to points b and c above because of their voltage dependence, pharmacology, and time constants. A correlate of point a was also probably present but difficult to resolve owing to the fast time constant of activation for the slow inward channel. At voltages negative to -50 mV a new voltage-dependent process could be resolved, which, because of its voltage dependence and time constant, appeared to represent the pacemaker channel (also termed If or IK2). In the Appendix, linear models of voltage-dependent channels and ion accumulation/depletion are derived and these are compared with our data. Most of the above-mentioned processes could be attributed to voltage-dependent channels with kinetics similar to those observed in time domain, voltage-clamp studies. However, the frequency domain correlate of the decline of the slow inward current was incompatible with channel gating, rather, it appears accumulation/depletion of calcium may dominate the decline in this preparation. PMID- 4041539 TI - Equilibrium muscle cross-bridge behavior. Theoretical considerations. AB - We have developed a model for the equilibrium attachment and detachment of myosin cross-bridges to actin that takes into account the possibility that a given cross bridge can bind to one of a number of actin monomers, as seems likely, rather than to a site on only a single actin monomer, as is often assumed. The behavior of this multiple site model in response to constant velocity, as well as instantaneous stretches, was studied and the influence of system parameters on the force response explored. It was found that in the multiple site model the detachment rate constant has considerably greater influence on the mechanical response than the attachment rate constant. It is shown that one can obtain information about the detachment rate constants either by examining the relationship between the apparent stiffness and duration of stretch for constant velocity stretches or by examining the force-decay rate constants following an instantaneous stretch. The main effect of the attachment rate constant is to scale the mechanical response by influencing the number of attached cross bridges. The significance of the modeling for the interpretation of experimental results is discussed. PMID- 4041540 TI - Fluorescence emission spectroscopy of 1,4-dihydroxyphthalonitrile. A method for determining intracellular pH in cultured cells. AB - We have developed new methodology for measuring intracellular pH (pHi) in cultured cell monolayers and epithelia by analyzing the emission spectra of the trapped fluorescent pH probe, 1,4-dihydroxyphthalonitrile (1,4-DHPN). This compound is unique since both its acid and base forms possess different fluorescence emission characteristics that can be used to quantitate pHi. The fluorescence difference spectrum between an acid and alkaline solution of 1,4 DHPN has a maximum at 455 nm and a minimum at 512 nm. By determining the ratio of the intensity at these two wavelengths as a function of pH, a calibration curve was constructed. Since the two intensities are determined simultaneously, the measurement is independent of dye concentration, bleaching, and intensity fluctuation of the excitation source. Furthermore, analysis of the emission spectra permitted the detection of light scattering, binding effects, and chemical modification of the probe. A microspectrofluorometer was constructed to analyze low light level emission spectra from intracellular 1,4-DHPN. The instrument consists of a modified Leitz inverted microscope (E. Leitz, Inc., Rockleigh, NJ) with a Ploem illuminator adapted for broadband excitation and objective focusing capability. The emission spectra were collected by focusing the fluorescence from the cell onto the entrance slit of an imaging monochromator, which was scanned by a SIT camera interfaced with a computer. This permitted the acquisition of fluorescence emission spectra extending from 391-588 nm in approximately 33 ms. pHi measured in the cultured toad kidney epithelial cell line, A6, was 7.49 +/- 0.04 (n = 12) with an external pH of 7.6. A6 cells were found to regulate pHi in response to both acute acid and alkali loads and maintained pHi relatively constant over a wide range of external pH values. The technique described in this report overcomes several of the difficulties encountered with other fluorescent pH probes where excitation spectroscopy is required to monitor pH. PMID- 4041541 TI - Capacitative transients in voltage-clamped epithelia. AB - In voltage-clamped epithelia the cell membrane potential transient during a + 10 mV transepithelial pulse conforms to the expected behavior for a series combination of two linear resistance-capacitance (RC) circuits. The evolution of the cell potential is characterized by a single time constant with values of 30 130 ms in frog skin and Necturus gallbladder. These observations have important consequences for the measurement of cell membrane resistance ratios and the interpretation of current-voltage relations. PMID- 4041542 TI - On a mechanism of cardiac electrical stability. The fractal hypothesis. AB - Electrical activation of the ventricles via the His-Purkinje system is represented on the body surface by a waveform with a broad range of frequency components. We speculate that this process is mediated by current flow through a fractal-like conduction network and therefore that the broadband spectrum of the depolarization waveform should be scaled as a power-law distribution. The prediction is confirmed by Fourier analysis of electrocardiographic data from healthy men. This observation suggests a new dynamical link between nonlinear (fractal) structure and nonlinear function in a stable physiologic system. PMID- 4041543 TI - Estimation of intracellular [Ca2+] by nonlinear indicators. A quantitative analysis. AB - When spatial gradients of intracellular free [Ca2+] are present, intracellular calcium indicators that have a nonlinear response to [Ca2+] may yield an estimate of [Ca2+] that differs from the spatial average [Ca2+]. We present two rules that provide (a) general criteria to distinguish those classes of indicators that will yield an overestimate of spatial average [Ca2+] from those that will yield an underestimate, and (b) limits on the extent to which spatial average [Ca2+] might be over- or underestimated. These rules are used to interpret quantitatively the aequorin luminescence signals obtained from cardiac ventricular myocardium. PMID- 4041544 TI - Prediction of the native conformation of a polypeptide by a statistical mechanical procedure. I. Backbone structure of enkephalin. PMID- 4041545 TI - Use of buildup and energy-minimization procedures to compute low-energy structures of the backbone of enkephalin. PMID- 4041546 TI - Amide I band of IR spectrum and structure of collagen and related polypeptides. PMID- 4041547 TI - Raman spectroscopic elucidation of DNA backbone conformations for poly(dG dT).poly(dA-dC) and poly(dA-dT).poly(dA-dT) in CsF solution. PMID- 4041548 TI - Theoretical study of the binding of aliphatic diamines to the minor groove of a B DNA (dA-dT)11 oligomer. PMID- 4041549 TI - Compressibility of lysozyme in solution from time-resolved brillouin difference spectroscopy. PMID- 4041550 TI - Binding of CC-1065 to poly- and oligonucleotides. PMID- 4041551 TI - Theory of gel electrophoresis of DNA. PMID- 4041552 TI - Expressions for the interpretation of circular intensity differential scattering of chiral aggregates. PMID- 4041553 TI - Molecular recognition. I. Automatic identification of topographic surface features. PMID- 4041554 TI - Structure-activity relationship of a bitter diketopiperazine revisited. PMID- 4041555 TI - First-pass elimination of lidocaine in the rabbit after peroral and rectal route of administration. AB - Lidocaine shows pronounced first-pass metabolism upon peroral administration in man (about 30 per cent peroral bioavailability). Since the rectal bioavailability is about 65 per cent in man it is assumed that some drug is directly absorbed into systemic circulation by-passing the liver. In rats peroral bioavailability is about 8 per cent whereas rectal bioavailability is about 100 per cent. This indicates that the rat is not a suitable model to study rectal lidocaine dosage forms. The purpose of this study was to investigate lidocaine disposition and bioavailability in rabbits after peroral and rectal administration. The peroral bioavailability in rabbits was found to be about 6 per cent and the rectal bioavailability is about 33 per cent. The results indicate that the rabbit is a suitable model for the study of systemic absorption of rectal lidocaine dosage forms. PMID- 4041556 TI - Pharmacokinetics and pharmacodynamics of bromocriptine in the rat. AB - The absorption, distribution, and excretion of bromocriptine were studied following oral and parenteral administration of non-radioactive and 14C-labelled drug in the rat. Total radioactivity was measured in blood, tissues, and excreta by liquid scintillation counting while the parent drug was determined in plasma and selected tissues by radioimmunoassay. The pharmacokinetic observations were compared with the time course of drug-induced hypothermia in cold-room acclimatized rats. The results indicated that oral doses of bromocriptine were rapidly, though incompletely (32-40 per cent), absorbed, but underwent extensive first-pass metabolism, resulting in an absolute bioavailability of only 6 per cent. The bioavailability increased to approximately 22 per cent in rats pretreated with the hepatic microsome inhibitor proadifen, thus suggesting the liver as the principal site of biotransformation. Absorbed bromocriptine showed preferential distribution into the tissues, although no apparent accumulation of drug-related material occurred in the body. The drug was eliminated almost exclusively by metabolism and biliary excretion into the faeces. Comparison of the pharmacodynamic and the pharmacokinetic profiles indicated a dose relationship between hypothermia and plasma bromocriptine concentrations but not total radioactivity levels. The hypothermic response was also intensified by proadifen pretreatment, thus confirming the parent drug as the pharmacologically active entity. It is believed that the previously reported delay in the onset of bromocriptine activity is not pharmacokinetic in nature, but is related to the properties of the receptors at the target site or to the pharmacologic events that result in the observed effects. PMID- 4041557 TI - Comparison of fitting methods for the analysis of plasma concentration-time data resulting from constant rate intravenous infusion. AB - Plasma concentration-time data resulting from constant rate intravenous infusion may be analysed in two ways: Samples may be collected both during and after infusion and fit to an infusion model. Samples may be collected after infusion is complete and the data may be fit as an i.v. bolus. The purpose of this study was to contrast these two fitting procedures in terms of the accuracy of the parameter values obtained. Concentration-time data were computer-generated with the introduction of random error to simulate the disposition profiles of two model drugs. The results of these simulations indicate that satisfactory values for area-dependent parameters may be obtained without fitting data during the infusion phase. The exception to this is the apparent steady-state volume whose values become less accurate with longer infusion times. The parameters most affected by ignoring data points in the infusion phase are the central volume of distribution, and the coefficient and disposition rate constant associated with the initial, rapid phase of disposition. The equation which describes the entire concentration-time profile provides the most accurate parameter estimates of the model equation. In addition, we also describe the influence of the fitting method on the intercompartmental transfer rate constants. PMID- 4041558 TI - Comparative physiological disposition of some anthraquinone glycosides and aglycones. AB - The in vitro microbial degradation and the urinary excretion and biliary secretion in rats of two anthraquinone glycosides (sennosides A and B) and four aglycones (sennidins A and B, rhein, and danthron) were studied using a high performance liquid chromatographic system with gradient elution and amperometric detection. Microbial degradation of sennosides A and B occurred almost exclusively in the presence of mice caecum inoculae and was associated with the release of sennidins A and B. Rhein and danthron were indiscriminately metabolized by bacteria sampled from all regions of mice intestine, whereas sennidins lacked stability in biological media. The fraction of the dose administered orally to rats and recovered as aglycones or as glucuronides in bile and urine after 48 hours was five times greater for rhein (15 per cent) and danthron (13.4 per cent) than for sennosides A (1.8 per cent) and B (2.8 per cent) excreted or secreted as sennidins. These results support the concept that anthraquinone glycosides are less likely to enter the systemic circulation and, thus, are able to exert their laxative effect at lower doses than aglycones. PMID- 4041559 TI - A pharmacokinetic model for prednisone after infusion to steady-state in the rabbit. PMID- 4041560 TI - Theoretical decrease in systemic availability with decrease in input rate at steady-state for first-pass drugs. PMID- 4041561 TI - Effect of variations in urine pH and flow rate on cimetidine renal disposition in man. PMID- 4041562 TI - Effect of glucagon on hepatic phenylalanine hydroxylase in vivo. AB - Moderate doses of glucagon (20 micrograms/kg I.V.) are sufficient to stimulate rat hepatic phenylalanine hydroxylase in vivo. In addition, the stimulation of the tetrahydrobiopterin-dependent phenylalanine hydroxylase activity in livers of animals fed on a high-protein diet has been correlated with an elevated phosphate content. The tetrahydrobiopterin-dependent hydroxylase activity in these animals can be further elevated by glucagon-stimulated phosphorylation. These results indicate that physiological changes in glucagon concentration modulate rat liver phenylalanine hydroxylase activity in vivo. The current understanding of the role of phosphorylation in regulating human phenylalanine hydroxylase is also considered. PMID- 4041563 TI - Hydrolysis of phosphatidylcholine liposomes by lysosomal phospholipase A is maximal at the phase transition temperature of the lipid substrate. AB - We have measured the rate of hydrolysis of liposomes made of DL-alpha dipalmitoylphosphatidylcholine (DPPC) and L-alpha-dimyristoylphosphatidylcholine by a soluble fraction of highly purified lysosomes isolated from rat liver. Phospholipids are hydrolyzed into lysophospholipids and fatty acids at a rate which is maximal near the temperature characteristic of the gel to liquid crystalline phase transition of the lipid bilayer. This strong influence of the physical properties of the substrate on the enzyme activity suggests a structural analogy between the lysosomal phospholipases of the A type (EC 3.1.1.32 and EC 3.1.1.4) and the pancreatic phospholipase A2. PMID- 4041564 TI - Cell-free translation of mitochondrial nicotinamide nucleotide transhydrogenase. AB - Mammalian nicotinamide nucleotide transhydrogenase is translated as a 5000 daltons larger molecular weight precursor in a cell-free system programmed with rat liver polysomes. The mature rat liver enzyme had the same molecular weight as the purified beef heart enzyme, 115 000 daltons. The precursor was not processed in vitro by liver mitochondria or by a rat liver mitochondrial matrix fraction, nor did it appear to bind to mitochondria. In contrast, pre-FeS protein of the cytochrome bc1 complex was processed in the same samples by both mitochondria and matrix, suggesting an important difference in the processing mechanisms or in the efficiency of processing of the two precursors. PMID- 4041565 TI - Biosynthesis of trehalose by Brevibacterium flavum: use of long range 13C-13C coupling data to characterize triose phosphate isomerase activity. AB - The 13C isotopic labeling pattern in the disaccharide trehalose (1,1'-alpha-alpha D-glucose) produced by the microorganism Brevibacterium flavum when grown on a medium containing [1-13C]glucose has been determined. Long range coupling between C-1 and C-6 carbons of the glucose units can be observed in the excreted material. It is proposed that some of the 13C isotopomers in the excreted trehalose reflect the labeling pattern in (unobserved) fructose 1,6-diphosphate. Analysis of the label distribution within the framework of a steady state kinetic model allows an analysis of the contributions of the hexose monophosphate shunt and the degree of equilibration of triose phosphate isomerase. Analogous measurements on excreted glucose could be carried out in other organisms. PMID- 4041566 TI - Accelerated degradation of glycogen phosphorylase in denervated and dystrophic mouse skeletal muscle. AB - Pyridoxal phosphate, the cofactor of glycogen phosphorylase, fulfils the criteria needed of a turnover label for this enzyme. The decay of protein-bound label following administration of [3H]pyridoxine is a good index of the rate of degradation of the enzyme in vivo. This method has been applied to the study of catabolism of the enzyme in normal, denervated and dystrophic mouse skeletal muscle. In both of the pathological conditions the enzyme is degraded more rapidly than normal. PMID- 4041567 TI - A characterization of haem uptake and intracellular distribution by isolated hepatocytes. AB - The uptake and intracellular distribution of haem by isolated rat hepatocyte suspensions was studied. An increase in cell haem content occurred after a challenge with 5, 10 or 20 microM haem, supplied as methaemalbumin. The rate of haem uptake was temperature dependent; no non-specific binding occurred. Intracellular haem distribution data are consistent with a rapid association of haem with the endoplasmic reticulum fraction prior to its accumulation in the cytosol and at the mitochondrion. PMID- 4041568 TI - Interaction of tyrosine residues with the chromophore in bacteriorhodopsin. AB - We previously reported that the absorption spectrum at low temperatures of iodinated bacteriorhodopsin can be separated into four components with maxima at shorter wavelengths than in native bacteriorhodopsin. In this study, the time course of the formation of each spectral component after iodination was analyzed, revealing that these four components correspond to four different iodinated states of tyrosine residues interacting with the retinal chromophore of bacteriorhodopsin. Therefore at least two tyrosine residues interact with the chromophore of bacteriorhodopsin. PMID- 4041569 TI - An International System for Human Cytogenetic Nomenclature (1985) ISCN 1985. Report of the Standing Committee on Human Cytogenetic Nomenclature. PMID- 4041570 TI - Accurate diagnosis and assessment of growth in patients with orofacial clefting. PMID- 4041571 TI - Diagnostic accuracy: effect on treatment planning. Proceedings of the Seventh Annual Symposium of the Society of Craniofacial Genetics. Denver, Colorado, June 17, 1984. PMID- 4041572 TI - The use of COMFORTS in a genetics clinic. AB - COMFORTS adequately meets the criteria that led to the establishment of FOMERS: data on patients are cross-indexed by name, diagnosis, and pedigree number. However, because COMFORTS utilizes the memory and sorting capabilities of a computer, it is more easily used for large databases than is FOMERS. Alphabetizing records by name in a file; adding, deleting, or modifying diagnostic categories; and assigning and sequencing pedigree numbers are easy when the work is shared with a computer. The ease with which data can be entered, changed, or deleted was shown in the foregoing description of the program. Ease of use is only one aspect of COMFORTS; expanded facility for research is equally important. Of particular interest in this latter regard is the Cardinal Sign field of COMFORTS. COMFORTS also has features that facilitate scheduling and generation of demographic reports. PMID- 4041573 TI - A new autosomal recessive syndrome with Noonan-like phenotype, myopathy with congenital contractures and malignant hyperthermia. PMID- 4041575 TI - Crouzon syndrome with periapical cemental dysplasia and acanthosis nigricans: the pleiotropic effect of a single gene? PMID- 4041574 TI - Chromosomal diagnosis of the Werner syndrome. PMID- 4041576 TI - Terminal transverse defects with aplasia cutis congenita (Adams-Oliver syndrome). PMID- 4041577 TI - Upper airway obstruction in craniofacial anomalies: diagnosis and management. AB - Particular attention to airway problems must be paid to any child with a craniofacial anomaly. Knowledge of the potential for upper airway obstruction in children with craniofacial anomalies, early recognition of the signs of obstruction, and prompt treatment are extremely important aspects of the treatment plan for each patient. An infant with choanal atresia or a nasal glioma will need definitive repair of his specific deformity to ensure the airway prior to consideration of any other problem. Similarly, the child with severe mandibular hypoplasia may require an early tongue-lip adhesion or tracheotomy to relieve airway distress until mandibular growth or surgical advancement enlarges the natural airway. Adenotonsillar hypertrophy may present earlier and with more severe sleep apnea in a child with an already compromised pharyngeal lumen. Early tonsillectomy and/or adenoidectomy must be considered in these patients even if this may possibly lead to velopharyngeal incompetence. Sleep apnea may also occur as a complication of the creation of a pharyngeal flap. If operative intervention for the craniofacial anomaly is contemplated, the potential for airway problems increases. The anesthetic induction and intubation are extremely difficult in the child with mandibular hypoplasia. The anesthetist and otolaryngologist must have a full range of techniques available to them to accomplish this task. If intermaxillary fixation is required postoperatively, or if the endotracheal tube is in the operative field, consideration should be given to a short-term tracheotomy to protect the airway during and after the operation. Close cooperation among the members of the craniofacial team is mandatory to prevent and/or treat any upper airway obstruction that may occur in the child with a craniofacial anomaly. Anticipation of possible airway compromise, early recognition of any existing obstruction, and prompt management of the problem are imperative to the successful diagnosis and treatment of craniofacial anomalies. PMID- 4041578 TI - Communicating the diagnosis to the deaf family. PMID- 4041579 TI - Achondroplasia and obstructive sleep apnea: correction of apnea and abnormal sleep-entrained growth hormone release by tracheostomy. AB - Severe obstructive sleep apnea in a patient with achondroplasia syndrome was found to result in a definitive deficiency of overnight growth hormone secretion related to absence of slow-wave sleep. Resolution of the apnea by tracheostomy resulted in normalization of growth hormone release and normal growth rates postoperatively. Sleep-related growth hormone deficiency may contribute to the short stature so often seen in a variety of craniofacial syndromes. Furthermore, this short stature may be reversible. PMID- 4041580 TI - The influence of L-sorbose on red cell flow properties, shape and packing ability. AB - Since the sweet ketohexose L-sorbose causes overt hemolysis in dogs but not in man, we examined the possibility that L-sorbose induces a "prehemolytic state" of human red cells, manifesting itself as impairment of rheological red cell properties. After 2 hours incubation at 37 degrees C relative viscosity of red cell suspensions measured by radial spreading in filter paper and packing ability of red cells were normal. Incubation for 24 and 48 hours of red cells in media containing L-sorbose, glucose or no sugar showed that relative viscosity was best maintained in glucose. Relative viscosity and packing ability of red cells in L sorbose containing suspensions decreased less than in suspensions without sugar. This difference was independent of the glucose metabolism, red cell ATP, osmolality and pH of the suspending media, but appeared to be related to different degrees of spheroechinocytic red cell shape transformation observed in different suspending media. It is possible that L-sorbose has some antiechinocytic properties and/or that it induces an alteration of red cell membrane flexibility. There is no indication of an L-sorbose induced "prehemolytic state" in human red cells. PMID- 4041581 TI - First haemorheological experiment under zero gravity on space shuttle 'Discovery'. PMID- 4041582 TI - Abstracts of seventh annual meeting, Japan Society of Biorheology. Sapporo, Japan, 16-17 June 1984. PMID- 4041583 TI - [Effect of elevated systemic arterial pressure on neurogenic vasoconstriction in the microcirculatory bed of rat skeletal muscles]. AB - Vasomotor reactions produced by electrical stimulation of the sympathetic tract were studied in anesthetized rats by intravital microscopy of the skeletal muscle (extensor hallucis proprius). Experiments were made in normal and elevated blood pressure. The stimulation itself did not change BP but led to an appreciable decrease in the initial diameter of the arterioles (28.6 +/- 1.4 m). The constriction amounted to 21%. The lumen decreased by 38.9%. Injection of felypressin (Sandoz) in a dose of 6 to 8 IU/100 g produced the pressor reaction. The 27.4% rise of BP during primary phase of the pressor response inhibited the development of the neurogenic vasoconstriction which was 11.5% for arteriolar diameter and 20.4% for lumen. The data suggest that inhibition of the neurogenic vasoconstriction is caused by an increase in arteriolar pressure. Consequently the elevation of intralumen pressure is considered as a protective mechanism of the drop of the tissue blood flow because of the sympathetic vasoconstriction. PMID- 4041584 TI - [Motor reactions in rats during critical growth periods in the early postnatal age]. AB - Within the first days after birth, the sleeping rats demonstrate the high rate of motor reactions (RMR) of the jerk type. With advancing age the RMR diminishes. However during a sudden change in the growth, the 25-day-old rats show an increase in the RMR of the jerk type. This is manifested by the return of the functions to the state marking the first days of life. The catecholaminergic mechanisms of the growth and development of rats are discussed. PMID- 4041585 TI - [Modulating influence of the 2d somatosensory cortex of the cerebral cortex on the effects of electroacupuncture on the trigeminal nuclei]. AB - The effect of reversible functional inactivation of the second somatosensory cortex of the cerebral hemispheres on changes in the transmission of the afferent signals in the trigeminal nuclei after electroacupuncture was studied in acute experiments on adult cats anesthetized with hexenal (59 mg/kg i. p.). After functional inactivation of the second somatosensory cortex electroacupuncture failed to facilitate the evoked potentials in the oral trigeminal nucleus by stimulation of the tooth pulp and the lip of the mouth. In the caudal nucleus, the inhibitory effect of electroacupuncture on noxious stimulation decreased. The involvement of this brain cortex in the mechanisms of action of electroacupuncture on functionally different nuclei is discussed. PMID- 4041586 TI - [Effect of alpha-tocopheryl acetate on blood biochemical parameters in albino rats as affected by acoustic stress]. AB - Experiments on random-bred white male rats have demonstrated the activation of induced lipid peroxidation in red cell membranes, elevation on the basal level of plasma lipid peroxides, a decrease in the content of alpha-tocopherol in plasma and red blood cell membranes, considerable shifts in the content of esterified and free cholesterol in plasma and red blood cell membranes under prolonged acoustic stress (91 dB). Administration of alpha-tocopheryl acetate in a dose of 1 mg/kg exerted a beneficial effect on the test parameters under prolonged acoustic stress. PMID- 4041587 TI - [Effect of lithium salts on neuropathological syndromes of spinal origin]. AB - Experiments on noninbred rats were made to study the influence of lithium hydroxybutyrate on two patterns of spinal cord pathology: the generalized myoclonus and painful syndrome of spinal origin. The syndromes were induced by generators of pathologically enhanced excitation in the ventral and dorsal horns of the spinal cord. The effects of lithium chloride and sodium hydroxybutyrate were examined to compare the influence of lithium (cation) and hydroxybutyrate (anion) components to elucidate the role of each of the components. Lithium hydroxybutyrate appeared more effective, since it inhibited the generator of pathologically enhanced excitation in the appropriate structures, provoking the anticonvulsant effect in myoclonus and suppressing the painful syndrome. PMID- 4041588 TI - [Change in the RNA polymerase activity in heart and liver cells during immobilization stress]. AB - Immobilization stress produces changes in the activity of polymerase I and II RNA in heart and liver cells. At the beginning of the poststressor reaction of the body the activity of both enzymes is lowered. Later on the activity of polymerase I RNA considerably exceeds the control level, whereas the activity of polymerase II RNA returns to the initial values. PMID- 4041589 TI - [Hemodynamic changes in immobilization stress]. AB - In chronic experiments on 75 Wistar, August and randombred rats hemodynamic changes were examined during 30-hour immobilization stress. The ECG was recorded and arterial blood pressure measured. The basic hemodynamic characteristics were determined with the help of the previously implanted ultrasonic blood flow probes. Analysis of hemodynamic changes in animals resistant, adapted and prone to stress demonstrated that changes in the total peripheral resistance play the leading role in the disturbance of the arterial blood pressure control. It was established that a progressive lowering of arterial blood pressure resulting from the abruptly reduced total peripheral resistance is the main and the most frequent cause of death of animals exposed to immobilization stress. At the same time the cardiac hemodynamic component may play an essential role in the mechanism of death. This component may include either progressive bradycardia or a combination of an ischemic myocardial damage and reduced total peripheral resistance. PMID- 4041590 TI - [Activation of lipid peroxidation processes in chronic ischemic heart disease]. AB - The content of lipid peroxidation products--hydroperoxides with conjugated double bonds and fluorescent compounds, which are formed on interaction of primary lipid peroxidation products and proteins, considerably increases in blood plasma of patients suffering from coronary heart disease. Treatment with combined vitamins E and C enables the blood plasma lipid peroxidation products to be decreased to a far greater extent as compared with conventional therapy. PMID- 4041591 TI - [Pulmonary circulation in different gaseous media]. AB - The ultrasonic method was used in acute experiments on cats with an open (under artificial lung ventilation) and closed chest to explore lung circulation in a changed gaseous medium. Moderate hypoxia (10% O2) and hypercapnia (5, 10% CO2) induce a 10-15% decrease in the lung blood flow in the inferolobular pulmonary artery in the presence of unchanged or slightly elevated minute volume of the heart. The higher hypoxia (5% O2) provokes inconclusive changes in the lung blood flow: biphasic response or increase. It is assumed that considerable elevation of blood pressure in the common pulmonary artery in all the cases points to vasoconstriction that occurs under the effect of hypoxia and hypercapnia. PMID- 4041592 TI - [Oscillatory evoked potentials in the rabbit visual system during experimental retinal pathology induced by administration of monoiodoacetic acid]. AB - ERG and EP of the visual cortex (VC) and superior colliculus (SC) were investigated under experimental dystrophy of the retina induced by intravenous injection of monoiodoacetic acid in different doses. The relative resistance of the VC to the derangement of retinal function was established. It was manifested by less marked suppression of its EP as compared with ERG. Taking into consideration the selective projection to the SC of the rod system that was damaged to a greater degree under pathology in question, it is suggested that functional suppression of the SC might facilitate the conduction of visual information through the main retino-geniculo-cortical canal. This might be one of the factors of VC resistance to the impairment of retinal function. This assumption was confirmed in experiments with SC electrocoagulation in which one could observe the facilitation of EP formation of the contralateral VC. PMID- 4041593 TI - [Dynamics of indices of the rat endocrine and lymphatic systems during cold adaptation]. AB - A study was made of the content of corticosterone, thyroxine and triiodothyronine in the blood, of the thymic weight and cytomorphological characteristics of rat lymph nodes during prolonged cold (4-5 degrees C) adaptation. Interrelated alterations in the characteristics under study were revealed at different stages of adaptation. The morphofunctional recovery of the lymphoid tissue occurs in the phase of the increased specific stability in spite of the fact that the action of cold is continued and the blood corticosterone concentration is elevated. A new type of the endocrine-lymphoid relationships is supposed to be formed during lengthy adaptation, with this type being different from that both in the starting state and acute stress. PMID- 4041594 TI - [Changes in the blood microcirculation in the mouth mucosa in experimental stomatitis]. AB - Aphthous lesions in the oral mucosa (OM) were simulated in dog experiments by ligation of the common bile duct. In one of the experimental groups the beta adrenoblocker propranolol was administered 30 min before surgery. Two hours after surgery the animals manifested changes in blood microcirculation of the OM. In animals treated with propranolol, the characteristics of blood microcirculation remained within normal. It is concluded that the development of aphthous lesions is preceded by functional disorders of blood microcirculation in the OM which are probably related to alterations in the neurovascular system. PMID- 4041595 TI - [Effect of alpha-tocopherol on the concentration of alpha-tocopherylquinone in human blood lipids]. AB - The electron-spin resonance (ESR) was applied to examine human plasma and red cell lipids. In the lipids, the signal of ESR of alpha-tocopherylquinone was recorded. The concentration of the latter in the lipids was found to be elevated in coronary heart disease. Intramuscular injection of 30% oily solution of alpha tocopherylquinone in a dose of 2 ml two times a day over three days entailed an increase in the concentration of alpha-tocopherylquinone in plasma and red cell lipids. PMID- 4041596 TI - [Accumulation of lipid peroxidation products in cataractous lenses]. AB - A study was made of the content of lipid peroxidation products (LPP) in the lenses extracted during operations for cataract as well as in transparent human lenses. In a mature cataract, the elevated content of primary, secondary and end products of lipid peroxidation (diene and triene conjugates, Schiff bases) was revealed. The content of LPP was identical in different clinical patterns of a mature cataract (senile, traumatic, complicated), which points to the universal role of lipid peroxidation in lenticular opacity. PMID- 4041597 TI - [Determination of double bonds in the lipid fraction of blood plasma in burn patients using the ADS-4M apparatus]. AB - An ADS-4M analyser was employed to study the diagnostic potentialities of the method for determination of double bonds (DB) in lipids of the burnt's blood as a rapid method for revealing alterations in unsaturated fatty acids (USFA). The method was tried in 25 patients with varying gravity of burn injury and in 15 healthy subjects with a purpose of establishing the norm. It was discovered that in patients with burn, the number of DB differed from normal depending on the disease gravity. The time course of changes in the number of DB attests to the necessity of the use of the method under consideration for evaluating abnormalities in the content of USFA. PMID- 4041598 TI - [State of the peripheral catecholaminergic systems during pharmacologic correction of immobilization stress using sodium oxybutyrate]. AB - Fluorescent microscopy and spectrofluorometry of biogenic amines were employed to study the peripheral catecholaminergic systems in immobilized rats which received sodium hydroxybutyrate. The content of catecholamines was measured in the adrenergic nerves of dura mater, vas deferens and chromaffin tissue of the adrenals. It was established that sodium hydroxybutyrate in a dose of 40 mg/kg intraperitoneally promoted returning to normal of the adrenergic mediator activity during alarm and resistance stages. The role of the peripheral catecholaminergic systems in the mechanism of the stress-protective effect of sodium hydroxybutyrate is discussed. PMID- 4041599 TI - [Study of the mechanism of the anti-hypoxic action of lithium oxybutyrate using cerebral ischemia as a model]. AB - A study was made of energy metabolism and concentration of malonic dialdehyde (MDA) in cerebral tissue of mice given sodium hydroxybutyrate and lithium hydroxybutyrate 30 and 60 s after decapitation. Administration of lithium hydroxybutyrate brought about a more economic consumption of the glycogen pool as compared with "hypoxic" control. The differences were revealed in the action of both salts on ATP. The concentration of MDA declined after their administration, lithium hydroxybutyrate being more efficacious. The possible mechanisms of the action of lithium hydroxybutyrate are discussed. PMID- 4041600 TI - [Change in the absorptive capacity of macrophages from different organs after administration of hydrocortisone]. AB - Two, twenty-four and 48 h after hydrocortisone treatment in a dose of 125 mg/kg bw the blood clearance rate for colloidal carbon particles in rats turned to be 2, 2.1. and 1.6 times less whereas that for 51Cr-SRBC in CBA mice 2.1, 2.2 and 1.7 times less as compared to untreated controls. Within 24 and 72 h after hormone injection the efficacy of red blood cell uptake by Kupffer cells decreased 1.35 and 1.8 times whereas the similar uptake by lung or spleen macrophages changed but insignificantly and that by bone marrow cells was even greater than in controls. Toward the 5th day after zymosan treatment the uptake capacity of Kupffer cells was the greatest whereas the plasma 11-OHCS content was 1.3-fold less versus the control values. PMID- 4041601 TI - [Role of antigen-binding cells in the formation of producers of antibodies and antigen-dependent nonspecific immunoglobulins]. AB - The role of antigen-binding cells in the formation of antigen-dependent nonspecific immunoglobulin producers in the Mishell-Dutton system was investigated. It was shown that the main part of antigen-dependent nonspecific immunoglobulin producers arise from the cells bearing antigen-specific receptors (as well as antibody producers). The nature of antigen-specific receptors of the precursors of antibody-forming and antigen-dependent nonspecific immunoglobulin forming cells is discussed. PMID- 4041602 TI - [Effect of hypolipidemic preparations on basal and stimulated adenylate cyclase activity in tumor cells]. AB - A study was made of the action of the antidiabetic biguanide phenformin, clofibrate and the phospholipid drug Essentiale on the basal and adrenaline stimulated activity of adenylate cyclase in Ehrlich's ascites carcinoma cells. All the drugs under study potentiated the hormone-stimulated activity of adenylate cyclase. Unlike phenformin and Essentiale, clofibrate did not exert any effect on the basal activity of adenylate cyclase. On the other hand, certain differences were revealed in changes of the lipid content of tumor cells during application of the drugs in question. Stimulation of adenylate cyclase activity by hypolipidemic drugs is regarded as a promising approach to the goal-oriented changing of hormonal sensitivity of tumor cells. PMID- 4041603 TI - [Interaction of alveolar macrophages with fibronectin during sensitization and anaphylactic shock]. AB - Interaction of rabbit alveolar macrophages (AM) with homologous fibronectin bound to gelatin-sepharose granules was studied. Macrophages obtained at the height of anaphylactic shock and cells from sensitized animals after preincubation with antigen or histamine failed to adhere to the fibronectin-coated surface. AM from intact and sensitized animals were capable of adhering to the fibronectin-coated granules in a Ca2+, Mg2+-dependent manner. Pretreatment of intact cells with trypsin inhibited AM-fibronectin interaction. The data indicate that the surface of AM bears protein receptors, capable of interacting with fibronectin, which change their affinity during anaphylactic shock and under the effect of histamine. It may be thus concluded that fibronectin is involved in the function of mononuclear phagocytes in health, evidence that complements the idea of the role played by macrophages in the pathogenesis of the immediate type hypersensitivity. PMID- 4041604 TI - [Differences in the rate of establishment of permanent estrus in rats after autotransplantation of the ovaries and as affected by other conditions]. AB - In adult female rats, constant light leads to the cessation of the sexual cycle and formation of permanent estrus after 6 to 7 days. In young animals, the sexual cycle was retained despite constant light and only after 3 months when the body weight of the rats reached 200-220 g the estrus became permanent. This happened earlier than in animals with the ovaries autotransplanted to the ears. The combination of constant light and autotransplantation of the ovaries caused an earlier formation of permanent estrus. It is marked that the same mechanism (the age-associated decrease of the cyclic center sensitivity to estrogen) underlies permanent estrus of various etiology. PMID- 4041605 TI - [Role of sex steroids and the pituitary in regulating the level of a specific estrogen-binding protein in rat liver]. AB - The effects of androgens (A), estrogens (E) and hypophysectomy on the content of an unusual rat liver estrogen-binding protein (UEBP) were studied by the differential quantitative method of the UEBP content measurement. The UEBP content was shown to increase during maturation of male rats. After A injections the UEBP content was high only in the liver of prepubertal but not of mature or immature males. Castration or hypophysectomy of mature males equally caused a decrease in the UEBP content in mature males whereas subsequent administration of A made it completely return to normal. Hypophysectomy of castrated males did not alter the UEBP content. A single injection of E provoked an appreciable reduction in the UEBP level after several days. Administration of A interfered with the inhibitory action of E after simultaneous injection of A and E and recovered the E-induced lowering of the UEBP content upon administration of A following E. Hypophysectomy of castrated males did not affect significantly the UEBP level. The UEBP content was insensitive to the direct action of pituitary factors. The pituitary is necessary for the realization of the effects of E alone but not A. It is suggested that the regulatory role of A consists in the maintenance of the constant optimal UEBP level in rat liver. PMID- 4041606 TI - [Structural and functional organization of the dorsal column nuclei after unilateral exclusion of the medial lemniscus]. AB - The authors studied ultrastructural changes in neurons and alterations in evoked electrical responses after stimulation of the forelegs in the nuclei gracilis and cuneatus one year after unilateral section of the medial lemniscus in cats. It was shown that intact projectional elements of the nuclei gracilis and cuneatus had the normal cytological appearance and functional activity of their synaptical organization in spite of the cytoarchitectonic asymmetry. After disruption of the medial lemniscus the symmetrical nuclei of the dorsal columns did not exhibit any asymmetry in the distribution of evoked responses after stimulation of the forelegs. PMID- 4041607 TI - [Morphological characteristics of tissue components of different layers of the rat myocardium]. AB - The tissue components of the subendocardial, inner and outer intramural layers of the myocardium were examined by morphometry. There was no significant difference in the proportion of cardiomyocytes in the different layers of the myocardium (subendocardium 0.820 +/- 0.007; inner layer 0.713 +/- 0.100; outer intramural layers 0.727 +/- 0.008; subepicardium 0.699 +/- 0.009). The relative surface of cardiomyocytes was maximal in the subepicardium (58.62 +/- 1,18). The magnitudes of the volumetric density and surface of the capillaries decreased from the subepicardial toward the subendocardial layer. The diameter of myocytes in the test layers of the myocardium varied within a wide range. PMID- 4041608 TI - [Morphological characteristics of changes in the skeletal muscle tissue of the extremities after experimental post-ischemic recirculation]. AB - The canine ischemic muscle tissue was subjected to a comprehensive morphological study after the recovery of the blood flow in the limbs for 2 hours. The effectiveness of of the recovery of the blood flow after the 3-hour ischemia was supported in acute experimental occlusion of the artery. The blood flow recovery after 6 hours of ischemia was associated with appreciable structural and metabolic abnormalities in the skeletal muscle fibers. These abnormalities were more demonstrable during recirculation after 9 and 12 hours of ischemia. No morphological criteria that might indicate whether the ischemic damage to the skeletal muscle is reversible or irreversible were defined. A comprehensive morphological study with an assay of structural and metabolic alterations is required instead. PMID- 4041609 TI - [Changes in the ultrastructure of rat hepatocytes at different periods after hepatic ischemia]. AB - The ultrastructure of rat hepatocytes was investigated at once at 30 min liver ischemia and at different periods after it. In 24 h of recirculation the processes of the recovery of hepatocyte ultrastructure dominated in the liver parenchyma, but even in 14 days of recirculation no complete reconstruction of hepatocyte ultrastructure was observed. PMID- 4041610 TI - [Possible approach to evaluating the energy potential of mitochondria in morphological studies]. AB - Based on histoenzymatic, cytospectrophotometric, electron microscopy and stereometric studies of the activity of mitochondrial enzymes and mitochondrial areas the authors developed integral indicators of the mitochondrial energy potential. The indicators permit forming a more concrete and complete judgement about the structural and functional status of the mitochondria and cell on the whole as well as about the contribution to the maintenance of intracellular homeostasis of individual substrates and components of redox processes, which widens the diagnostic and prognostic potentialities of the morphological and cytological assay. PMID- 4041611 TI - [Space-time sequence and mosaicism of neurogenesis in the CA1 field of the mouse hippocampus]. AB - Pregnant CBA mice were given a single injection of 3H-thymidine (3H-T) (10 microCi/g) on days 11-19 of pregnancy. The mouse progeny was sacrificed on the first day of postnatal life. Brain was embedded into paraffin and durcupan. Radioautographs of paraffin and semithin sections were prepared and employed for mapping the site of intensely labeled neurons (ILN) in the CAI area of the hippocampus (H). ILN appeared in the CAI area after 3H-T injection, namely on embryonic day 12 (E 12). The ILN number reached a maximum after isotope injection on 2 14-15 and then dramatically fell down. The neurogenesis in the suprapyramidal layer of the CAI area slightly outstripped the neurogenesis in the pyramidal and infrapyramidal layers. At early times of the experiment the CAI area exhibited the predominance of single ILN, whereas at late times paired ILN prevailed. That fact might be linked with the replacement during the neurogenesis of asymmetric critical mitoses of the germinative neuronal precursors by symmetric critical mitoses. Analysis of the ILN distribution in the CAL area revealed mosaic clusters of ILN alternating with unlabeled or mildly labeled neurons. Those groups were most remarkable in mice injected with 3H-T on E 14 and E 15. The mosaicism of the neurogenesis in the H is regarded as the result of heterochronous neuronal production by local parts of the germinative zone, each of which builds up a separate radial segment of the H. PMID- 4041612 TI - [Reactivity of mononuclear phagocytes in the lungs and liver of rats exposed to low temperatures]. AB - A study was made of lung and liver mononuclear phagocytes of rats exposed to severe cold (-7 degrees C). The data indicate the depression of mononuclear phagocytes under short-term (2 h) exposure to cold followed by activation of phagocytes, which was more demonstrable in the lungs. The phase modifications in the activity of mononuclear phagocytes were associated with accumulation of lipid peroxidation products (LPP) and destruction of alveolocytes. The different accumulation of LPP in the test organs of animals exposed to cold is regarded by the authors as a possible reason for functional differences of lung and liver macrophages. PMID- 4041613 TI - [Experimental data on the mechanism of development of alcoholic cardiomyopathy]. AB - A study was made of histo- and ultrastructure and of some electron-histochemical characteristics of the myocardium and liver of alcoholic rats. Experimental animals manifested alterations in the myocardium which were similar to those seen in alcoholic cardiomyopathy in humans. In controls, such alterations were either lacking or occurred in rare cases. Rats which received ethanol showed fatty dystrophy of the liver. The experimental animals differed from controls in some morphometric parameters (body and heart weight, diameter of cardiomyocytes) as well. PMID- 4041614 TI - [Hemobacterial agglutination--method of determining antierythrocyte antibodies]. AB - A technique of antierythrocyte antibody detection is described. It as based on co agglutination of red blood cells and S. aureus cells. The method is unsophisticated and non-laborious. It provides massive agglutination, its sensitivity is one order of magnitude higher than that of the Coombs test. PMID- 4041615 TI - [Method for electrodiagnosis of the necrotic zone in skeletal muscles]. AB - A simple new method for determination of necrosis of the skeletal muscles is suggested. Stimulation of the muscle and the recording of the contraction is made via a needle electrode. The contraction is recorded as a characteristic drop of the muscle resistance to high-frequency current which per se does not cause any stimulation. The zone of necrosis does not demonstrate any characteristic changes in the resistance. The presence of necrosis in the areas under exploration was proved histologically. PMID- 4041616 TI - [Masugi's nephritis: preparation of an active nephrotoxic serum]. AB - An active nephrotoxic serum (NTS) was prepared by immunization of rabbits with isolated renal glomeruli of rats and Freund's complete adjuvant. The glomeruli were isolated from the renal cortex by the sieving procedure. Intravenous injection of the NTS to rats induced the development of marked proteinuria and the nephrotic syndrome. Histological and electron microscopic studies of renal tissue performed by days 5 and 15 since the first injection of the NTS revealed extracapillary proliferative glomerulonephritis. IgG depositions on the basal membranes of the glomerular capillaries were linear on day 5 and granular on day 15 since the first injection of the NTS. PMID- 4041617 TI - Regulated proliferation of primitive hematopoietic progenitor cells in long-term human marrow cultures. AB - We have examined the cycling status of various classes of erythroid and granulopoietic progenitor populations maintained for many weeks in standard normal long-term human marrow cultures. These were initiated with a single inoculum of marrow aspirate and were routinely fed by weekly removal of half of the nonadherent cells and replacement of half of the growth medium. Progenitors of large erythroid colonies (more than eight erythroblast clusters) present in the nonadherent fraction and progenitors of small granulocyte/macrophage colonies (fewer than 500 cells) present in both the nonadherent and adherent fractions were found to be actively cycling at all times examined (28% to 63% kill following a 20-minute exposure to 20 microCi/mL of high specific activity 3H thymidine). In contrast, progenitors of large granulocyte/macrophage colonies (more than 500 cells) and progenitors of large erythroid colonies (more than eight erythroblast clusters), present in the adherent layer, consistently alternated between a quiescent state at the time of each weekly medium change and a proliferating state two to three days later (0% to 13% kill and 21% to 49% kill, respectively). Additional experiments revealed that the activation of primitive progenitors in the adherent layer was not dependent on the addition of fresh glutamine or hydrocortisone, nor on the physical manipulations involved in changing the growth medium. These studies provide the first direct evidence that normal long-term human marrow cultures support the continued turnover of a variety of early hematopoietic progenitor cell types. Further, they indicate that the proliferative activity of the most primitive of these progenitors is regulated by stage-specific cell-cell interactions that are subject to manipulation. PMID- 4041618 TI - Heparin cofactor II activity in patients with disseminated intravascular coagulation and hepatic failure. AB - Heparin cofactor II (HCII) is a glycoprotein in human plasma which inactivates thrombin rapidly in the presence of heparin or dermatan sulfate. We have developed a functional assay for HCII in which inhibition of thrombin by plasma is determined in the presence of dermatan sulfate. The assay is specific for HCII by the following criteria: (a) under the conditions of the assay, 125I-thrombin forms complexes in plasma which comigrate with the thrombin-HCII complex during sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE); (b) activity detected by the assay is decreased in plasma absorbed with monospecific antibodies against HCII; and (c) purified antithrombin III (ATIII) is unreactive in the assay system. Addition of Polybrene to the assay permits determination of HCII activity in samples containing less than or equal to 12 U/mL of heparin. The range of HCII concentrations in normal individuals is 1.2 +/- 0.4 mumol/L (mean +/- 2 SD, n = 34). HCII activity was determined in 54 consecutive patients undergoing evaluation for the possibility of disseminated intravascular coagulation (DIC). Ten of the 11 patients with documented DIC had decreased HCII activity as compared with only 7 of the 43 patients without DIC (chi 2 = 19.3, P less than .0001). The concentrations of HCII and ATIII varied in parallel in most of the patients tested. A significant correlation between decreased HCII activity and decreased serum albumin concentration was also observed in these patients and in eight additional patients with hepatic failure in the absence of DIC. We conclude that HCII activity is decreased in many patients with DIC and hepatic failure. PMID- 4041619 TI - Human platelet fibrinogen: purification and hemostatic properties. AB - Conditions were developed in which 80% to 90% of platelet fibrinogen could be routinely purified in nondegraded form from the fluid phase of platelet suspensions stimulated with the calcium ionophore, A23187, in the presence of calcium, leupeptin, and prostaglandin E1. Fibrinogen was separated from other released proteins by chromatography on diethylaminoethanol (DEAE)-cellulose using a continuous pH and ionic strength gradient. Purified platelet fibrinogen, greater than 98% homogeneous by immunoelectrophoresis and sodium-dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), consisted of intact A alpha, B beta and gamma A chains, but not gamma' chains, and was 95% to 96% clottable. Platelet fibrinogen was shown to compete for the binding of radiolabeled plasma fibrinogen to ADP-activated platelets in a manner identical to that of unlabeled plasma fibrinogen itself. Also, at equivalent protein concentrations, platelet and plasma fibrinogens supported platelet aggregation to an equivalent extent. Based upon these results, we conclude that there is no significant difference between platelet and plasma fibrinogen with respect to their size, their clottability, their affinity for the activated platelet fibrinogen receptor, or their capacity to support subsequent platelet aggregation. PMID- 4041620 TI - Acetylcholinesterase in human thymus cells. AB - Acetylcholinesterase (AChE) was long thought to be an enzyme found specifically at the sites of nerve synapses and neuromuscular junctions. It has also been found to occur, however, in cells that are not involved with neurotransmission. This study presents the ultrastructural localization of AChE activity in human thymus cells, using the indirect thiocholine method. Cytochemical demonstration of the enzyme was based on the coupling of acetylthiocholine iodide hydrolysis to the precipitation of heavy metal salts. AChE activity was selectively revealed in the perinuclear cisternae, within the endoplasmic reticulum, and in the Golgi complex of thymic lymphocytes and epithelial cells. Evidence of the presence of reaction product in the latter cells was also found in vesicles that opened into the extracellular space. This is the first demonstration of AChE in human thymus cells. Its possible physiologic role in the thymus gland is discussed. PMID- 4041621 TI - The acetylcholinesterase defect in paroxysmal nocturnal hemoglobinuria: evidence that the enzyme is absent from the cell membrane. AB - Paroxysmal nocturnal hemoglobinuria (PNH) is a myelodysplastic disease characterized by erythrocytes that show abnormally increased sensitivity to complement-mediated lysis. Complement-sensitive PNH erythrocyte membranes have previously been shown to lack acetylcholinesterase (AchE) activity, but the molecular basis of this deficiency has been unclear. We have used monoclonal antibodies to four different epitopes on the AchE molecule to show that abnormal PNH erythrocytes failed to bind these antibodies. Moreover, abnormal PNH erythrocytes contained no protein immunoprecipitable by these antibodies, while normal complement-insensitive erythrocytes from PNH patients showed normal amounts of immunoprecipitable AchE which had normal electrophoretic mobility. These data suggest that abnormal PNH erythrocytes lack AchE enzyme activity due to the absence of the AchE molecule from the cell membrane. PMID- 4041622 TI - Observations on the outcome of specialty education and training in forensic psychiatry. PMID- 4041623 TI - Reasonable medical certainty, diagnostic thresholds, and definitions of mental illness in the legal context. PMID- 4041624 TI - Can psychiatry contribute to gun control? PMID- 4041625 TI - Beyond the scientific limits of expert testimony. PMID- 4041626 TI - The consultation model and forensic psychiatric practice. PMID- 4041627 TI - Medical school forensic psychiatry units in health care delivery facilities rather than criminal justice institutions: an alternative model. AB - We have presented a model for developing forensic psychiatric treatment and teaching services of a medical school Department of Psychiatry, but where these services are the basic comprehensive health care delivery system for the entire community. These offer consultative and treatment services for adult and family court clinic, psychiatric forensic services, of forensic psychiatry open bed and medium security-type bed, as well as day hospital and outpatient services. All of these are sited in the normal health care delivery system of the university teaching hospitals and its patient treatment, teaching, and research facilities. Consultative services are offered on request to the criminal justice system, but the basic health care delivery system is controlled administratively by the ordinary university teaching hospital authorities and exists as a one of a kind unit at the Royal Ottawa Hospital. The Royal Ottawa Hospital is a private nonprofit hospital, with its own Board of Trustees, and is affiliated with the medical school, as part of a major university network. We believe it important to present this model for an overall forensic psychiatric service, in contradistinction to the more commonly established forensic psychiatric facilities in state mental hospitals, in a special facility for the criminally insane, or in a criminal justice system institution such as a penitentiary. We believe that our model for forensic psychiatric facilities has great advantages for the patient. Here the patient is treated in a specialized facility (as all psychiatric patients with specialized problems should be); but one which is a specialized forensic facility, within the range of specialized psychiatric facilities that are needed by an urban community.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4041628 TI - Sanctum sanctorum: the psychiatrist's role in postrial competency examination of jurors. PMID- 4041629 TI - Suicide litigation and risk management: a review of 32 cases. PMID- 4041630 TI - Children who witness violence: tortious aspects. PMID- 4041631 TI - A comparison between men charged with domestic and nondomestic homicide. PMID- 4041632 TI - Use of summons in involuntary civil commitment. PMID- 4041633 TI - Decision-making in child abuse and neglect. AB - Social attachment theory can be of value in examining the wide variety of abuse and neglect situations that come to the attention of authorities. We consider evaluation of the parent-child relationship as a crucial part of the judicial process. We have suggested parameters that can be used to evaluate the relationship. We have outlined some of the more common distortions in this relationship that have, in our experience, been associated with the mistreatment of children. The use of social attachment theory has been of great help in understanding the emotional reactions of the many children we have seen for evaluation and treatment. The theory also serves as a potential guide for improvements in social policy. If we are more sensitive to the psychological world of these children, we will be better able to truly protect them. PMID- 4041634 TI - Detecting child abuse by studying the parents. PMID- 4041635 TI - The role of unconscious conflict in informed consent. PMID- 4041636 TI - A case of child abandonment--reflections on criminal responsibility in adolescence. AB - The issue of responsibility for delinquent acts has been examined in the light of adolescence as a unique developmental stage, and it has been proposed that the degree to which one should hold an adolescent morally responsible for his/her acts corresponds to the degree to which he/she has individuated from his/her family and become a psychologic adult. A case was presented in which the crime of child abandonment was committed by an adolescent who was still deeply enmeshed interpersonally with her mother and had not yet achieved a separate identity as an adult. The psychiatric findings were presented to the Court after a plea bargain had been struck and prior to sentencing. They conveyed the belief, in lay terms, that moral responsibility for this crime was collective, to be borne in part by the perpetrator's family. The Court responded humanely with a suspended sentence, conditioned on psychotherapy, allowing the young mother to remain together with her first child. Not only does this article suggest the value of an understanding of adolescent psychiatric concepts for the forensic psychiatrist, it also suggests that the more subtle aspects of assigning responsibility can be better evaluated by the court at the time of sentencing than during the trial phase. PMID- 4041637 TI - Identification of fluchloralin in imported dried fruit. PMID- 4041638 TI - Identification of diazinon and its metabolite in spinach by chemical ionization mass spectrometry. PMID- 4041639 TI - Colorimetric determination of propoxur residues in vegetables and water. PMID- 4041640 TI - Activation of polycyclic aromatic hydrocarbons by hepatic S-9 from a marine fish. PMID- 4041641 TI - Acute toxicity of four phenoxy herbicides to aquatic organisms. PMID- 4041642 TI - Organochlorine hydrocarbon residues in sediments of two different lagoons of northwest Mexico. PMID- 4041643 TI - Effect of selenite on the uptake of methylmercury in cod (Gadus morhua). PMID- 4041644 TI - Effects of gut sediment contents on measurements of metal levels in benthic invertebrates--a cautionary note. PMID- 4041645 TI - Superficial accumulation of heavy metals in near shore marine sediments: an objective index of environmental pollution. PMID- 4041646 TI - Absorption of Cu++ by long-term cultures of Dunaliella salina, D. tertiolecta, and D. viridis. PMID- 4041647 TI - Daphnia magna as an indicator of the acute toxicity of waste waters. PMID- 4041648 TI - Effects of cold ambient temperatures on acute mortality of Peromyscus leucopus dosed with parathion. PMID- 4041649 TI - Hemolyzed, lyophilized bovine blood for quality control of lead determination of human whole blood. PMID- 4041650 TI - Factors associated with blood pressure in females with heavy exposure to cadmium. PMID- 4041651 TI - Tissue distribution of acetaldehyde in rats following acetaldehyde inhalation and intragastric ethanol administration. PMID- 4041652 TI - Extraction and analysis of chlordimeform and demethylchlordimeform from human tissue samples. PMID- 4041653 TI - Gas chromatographic determination of pentachlorophenol in human blood and urine. PMID- 4041654 TI - Serum organochlorine residues in Florida citrus workers compared to the National Health and Nutrition Examination Survey sample. PMID- 4041655 TI - Respiratory mucus production in asthma. PMID- 4041656 TI - Respiratory function in recent pulmonary sarcoidosis with special reference to small airways. AB - This study was designed to evaluate airway dysfunction in relation to duration of disease in patients with pulmonary sarcoidosis for less than two years. Twenty four subjects with recent disease were compared with nine subjects with disease of more than two years' duration. They underwent lung function testing (lung volumes, lung transfer factor for CO and pulmonary mechanics). Small airway function was assessed using frequency dependence of compliance, closing volume, nitrogen single breath test and flow-volume curves breathing air and helium oxygen mixture. Airway dysfunction was seen in pulmonary sarcoidosis even in some patients with recent disease and it became more evident in disease of longer duration. The results suggest small airway involvement. The frequency of airway dysfunction is difficult to evaluate, varying from estimates of 0% using flow volume curves to 79% with frequency dependence of compliance. This apparent discrepancy could be explained by the consequences of parenchymal involvement leading to inhomogeneities in distribution of compliance, and of elastic lung recoil. We conclude that patients with recent sarcoidosis are probably affected by intrinsic small airway disease, but an increase in elastic recoil often conceals its consequences. The airway disease may not be apparent using conventional function tests and published predicted values. PMID- 4041657 TI - Respiratory inductance plethysmography: calibration techniques, their validation and the effects of posture. AB - Respiratory inductance plethysmography (RIP) is used to measure ventilation from two measurements of body surface movements (rib-cage and abdomen) via the application of volume-motion (V-M) coefficients. The correct derivation of both V M coefficients (calibration) is necessary because there are considerable spontaneous variations in relative contributions from these two compartments even during resting breathing. In order to fully test a calibration, deliberate changes in rib-cage (RC) to abdominal (AB) contribution must be made. We used this approach to test two single-posture calibration techniques, multiple linear regression (MLR) and isovolume (ISV). Ten normal subjects and nine patients with chronic airway obstruction (CAWO) were studied using quiet breathing throughout. We also studied the effects of changing posture on the constancy of the V-M coefficients. MLR proved a little more accurate (p = 0.03) in deriving the V-M coefficients than ISV in normal subjects, and ISV consistently underestimated the AB V-M coefficient relative to RC. No difference between the two techniques existed in patients with CAWO. Both MLR and ISV calibrations failed to give acceptable calibrations in some patients. When MLR calibration was used, a deliberate 20% change in relative compartmental contribution (RC-AB) induced mean errors in RIP estimations of tidal volume of 3.5 and 9.5% in normal subjects and patients respectively. When there were no deliberate changes in relative contribution, the 95% confidence limits of individual tidal volume estimates were +/- 6.6 and +/- 12% in normal subjects and patients respectively. MLR calibration provides a statistical estimate of its quality at the time of V-M coefficient derivation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4041659 TI - Upper airway reflexes in newborns with respiratory distress syndrome. AB - In 16 newborns with respiratory distress syndrome (RDS) not artificially ventilated, oesophageal pressure was recorded with an electromanometer and the reactions to mechanical stimulation of the upper airways by means of a nylon fibre were investigated. The results were compared with the values obtained in 16 newborns without cardiorespiratory disturbances. The reactions were evoked by mechanical stimulation of the airways. Mechanical stimulation of the nasal mucosa produced expulsive reactions only in 45% of cases in newborns with RDS as compared with 95% in healthy newborns (p less than 0.001). Stimulation of the oropharyngeal and laryngeal regions elicited expulsive reactions in 48% of cases in newborns with RDS, but 74% in healthy newborns (p less than 0.001). In other cases, inhibition of breathing or apnoea was the most common reaction. The expulsive component of responses such as sneezing, expiratory reaction and crying was weaker in newborns with RDS than in control infants. The inspiratory component of sneezing and coughing, on the contrary, was stronger in newborns with RDS. These results indicate that active elimination of irritants from the airways is reduced in newborns with RDS. PMID- 4041658 TI - [Effects of sensitization to ovalbumin on the lipid content of the bronchoalveolar lavage fluid in guinea pigs]. AB - Four groups of guinea-pigs were studied (l1: control, l2: sensitized to ovalbumin, l3: sensitized and challenged by aerosol of ovalbumin, l4: challenged by aerosol of histamine). In urethane anaesthetized guinea-pigs, pulmonary resistances and dynamic compliance were measured (before and after aerosol of ovalbumin in l3 and aerosol of histamine in l4). The lungs were removed and the static pressure-volume curves were performed to determine lung compliance. In the pulmonary lavage fluids, surface tension and total fatty acids and phospholipids were measured by Cahn's electrobalance and gas chromatography respectively. In l2 guinea-pigs, the mean value of total fatty acids and of phospholipids was significantly decreased in pulmonary lavage fluid, by 24.5% and 40.2% respectively. Surface tension was increased while lung mechanics was identical to control. In l3 guinea-pigs, the mean value of total fatty acids and of phospholipids was significantly decreased in pulmonary lavage fluids, by 55.7% and 53.2% respectively. Surface tension was increased. In vivo, lung mechanics was changed: dynamic compliance decreased, pulmonary resistances increased. Pressure-volume curves were flattened and pulmonary compliance of isolated lungs was decreased since bronchial obstruction remained after death. In l4 guinea pigs, the mean value of total fatty acids and of phospholipids was increased in pulmonary lavage fluid but not significantly, by 26.6% and 9.2%. Surface tension was not changed. Lung mechanics was very significantly affected by bronchospasm, but after death the mechanics of the isolated lung and of control lung was identical. Finally, the decrease of surface-active lipids in pulmonary lavage fluid originates in the sensitization and is enhanced by antigen-induced bronchial anaphylaxis but not by histamine-induced bronchospasm. PMID- 4041660 TI - Muscle fibre types in costal and crural diaphragm in normal men and in patients with moderate chronic respiratory disease. AB - Histochemical muscle fibre composition of human costal and crural diaphragm was determined in biopsies sampled during surgical procedures. Two groups were studied: 10 subjects with normal lung function and 8 patients with chronic obstructive respiratory disease. Muscle fibres were classified as type I (slow twitch) or type II (fast twitch) on the basis of their myofibrillar ATPase pH lability. There was no significant difference in fibre proportions between costal diaphragm (COD) and crural diaphragm (CRD) for both groups of subjects. Yet, in the normal group, the diameters of both types of fibres were larger in COD than in CRD. The diameters of both types of fibres of the obstructive patients were significantly decreased in COD as compared to the normals. Moreover, linear correlations between type I and II fibre diameters and VC, FEV1, FEV1/VC, and body weight were found in COD and not in CRD. The differences found in muscle fibre size support the idea that the mechanical respiratory load is different for COD and CRD, COD being the more important force generator. Chronic obstructive respiratory disease causes a significant decrease in COD fibre size but does not affect CRD. PMID- 4041661 TI - Exercise performance of subjects with ankylosing spondylitis and limited chest expansion. AB - To examine the mechanism of exercise limitation associated with chest wall restriction (CWR), we compared the ramp (1 W/3 s) exercise performance of six untrained subjects with ankylosing spondylitis (AS) and six healthy subjects matched for age and body size. Subjects with AS had CWR (maximum rib cage expansion : 1.4 +/- 0.2 cm; means +/- sem). The maximum oxygen uptake (VO2max) of AS subjects (2.15 +/- 0.2 1-stpd) was less than their predicted VO2max (2.68 +/- 0.13 1-stpd; p less than 0.03) and the measured VO2max of matched healthy subjects (2.78 +/- 0.22 1-stpd; p less than 0.03). Subjects with AS achieved 95 percent of predicted maximum heart rate, and their maximum voluntary ventilation exceeded their maximum exercise ventilation by at least 15 l X min-1 unless parenchymal pulmonary disease was present. We conclude that maximum ramp exercise performance of AS subjects with CWR is decreased. Deconditioning or cardiovascular impairment rather than ventilatory impairment appears responsible for the observed reduction of VO2max. PMID- 4041662 TI - [Effects of histamine on the pressure-volume curve of the respiratory system in the guinea pig]. AB - Intravenous infusion of histamine has been shown to constrict smooth muscle of alveolar ducts. In this study, we have assessed the effects of a prolonged infusion of histamine to obtain a steady state response on quasistatic pressure volume curves (P-V curves) together with the changes in dynamic compliance (Cdyn) and conductance (G) of the respiratory system. Increasing doses of histamine were given in order to obtain the dose-response characteristics of the changes in Cdyn, G and P-V curves. In nine anesthetized guinea-pigs under mechanical ventilation, administration of histamine resulted in a fall in Cdyn and G with a decrease of 50% of initial value approximately for 150 ng X kg-1 X s-1 of histamine. Modifications of the P-V curves were characterized by a decrease in the maximal volume, and an increase in the hysteresis of the P-V loop due to the downward displacement of the inflation limb. With infusion of histamine, there was a large decrease of quasi-static compliance which appeared to account for most of the decrease in dynamic compliance. Such changes in P-V curves can be related both to a closure of alveolar ducts and to an alteration of lung distensibility. Comparison of the dose-response curves for the different parameters indicated that Cdyn and G reflect, at least in part, events occurring in the periphery of the lung. PMID- 4041663 TI - [Value of sleep polygraph examination in the etiological diagnosis of apparently inexplicable respiratory insufficiency]. AB - This study describes the case of a 58 year old man who presented with an episode of acute respiratory failure and right heart decompensation. After recovery from the acute illness, hypoxaemia, hypercapnia and pulmonary arterial hypertension remained, the causes of which were not known. There was no airway obstruction, only a moderate restrictive ventilatory defect, a little weight increase and a unilateral diaphragmatic paralysis. Obstructive sleep apnoea was finally suspected and confirmed by sleep recording. The obstructive sleep apnoea probably explained the respiratory insufficiency and the pulmonary hypertension. Loss of weight was associated with the disappearance of hypercapnia and pulmonary hypertension. As a result of this study, the value of sleep recording is emphasized. When respiratory failure or pulmonary hypertension seem unexplained, think of obstructive sleep apnoea. PMID- 4041664 TI - Assessment of changes in airway calibre using the body plethysmograph. AB - We set out to assess the contribution of errors in measurement of thoracic gas volume and the relationship between volume and conductance to the estimation of airway resistance and conductance. In three subjects, errors in thoracic gas volume were smaller by a computerized than a manual method, but were not great enough to have much effect on the variability of resistance and conductance. The conductance-volume relationship was very variable in 17 subjects; from this relationship, it was possible to predict whether conductance or specific conductance would be the more variable measurement in 16 out of the 17. Conductance-volume relationships changed markedly after bronchoconstriction with histamine in one out of three subjects. Overall we found specific conductance to be the most satisfactory measurement. This measurement can be made without estimation of thoracic gas volume by closure of the mouth shutter and can, therefore, be used to follow acute changes in airway calibre. PMID- 4041665 TI - Growth models (including terminal and segmental branching) for topological binary trees. PMID- 4041666 TI - Chaotic dynamics of information processing: the "magic number seven plus-minus two" revisited. PMID- 4041667 TI - On the computation of the tertiary structure of globular proteins--IV. Use of secondary structure information. PMID- 4041668 TI - The extension of two-dimensional cable theory to arteries and arterioles. PMID- 4041669 TI - The unidirectional flux transient as a tool for quantifying parallel diffusional pathways through membranes. Exact solution for two pathways. PMID- 4041670 TI - Getting a job: the interview. AB - The interview is a vital part of the process of selecting the best candidate for a hospital post from many suitable ones. Most doctors should be able to develop an interview technique that does justice to all their qualities. PMID- 4041672 TI - Manpower and training. PMID- 4041671 TI - Your accounts. Private practice--7. PMID- 4041673 TI - Refuge in the private sector. PMID- 4041674 TI - The Scrooge issue. PMID- 4041675 TI - The selective antagonism of bradykinin action on rat isolated uterus by crude Mandevilla velutina extract. AB - A crude aqueous alcoholic extract of Mandevilla velutina (Apocynaceae) rhizomes produced a concentration-dependent displacement to the right of the concentration response curve to bradykinin (Bk) in the isolated uterus of the rat. Schild analysis of the data revealed a linear relationship (r = 0.99) and yielded a pA2 value of 3.3 + 0.08 (- log g ml-1) but the slope differed significantly from unity. The anti-Bk action was of rapid onset and was reversible upon washout. Contractions induced by acetylcholine, oxytocin, angiotensin II and BaCl2 were unaffected by the extract. This represents the first report of a selective Bk antagonist of plant origin. The isolation of the active principle(s) may result in a useful pharmacological tool for elucidating the physiological and physiopathological roles of endogenous Bk. PMID- 4041676 TI - Simultaneous measurement of contractile effects in the circular and longitudinal smooth muscle of the rat vas deferens by drugs perfused externally or via the lumen. AB - The effects of noradrenaline and barium chloride were studied in the rat isolated vas deferens by perfusion of drugs either externally or through the lumen of the organ. Two effects were recorded simultaneously in the same preparation: (a) isometric contractions, due to the tension elicited by drugs on the external (longitudinal) smooth muscle layer and (b) pressure of internal perfusion, due to contractions of the internal (circular) smooth muscle layer. It was found with the longitudinal muscle that: (a) the potency, expressed as pD2 values, and the maximum response to noradrenaline were lower if the drug was perfused internally rather than externally; (b) the differences in maximum effects were pronounced on the prostatic half but were not observed on the epididymal half; (c) the maximum response obtained by internal perfusion could be increased by simultaneously adding the same dose of drug externally; (d) when barium chloride was used instead of noradrenaline no significant differences were observed on pD2 values, but differences on maximal responses were similar to that observed for noradrenaline; (e) it was possible to block completely the effect of internal or external noradrenaline on the longitudinal muscle, by perfusing external phenoxybenzamine. In these conditions the responses of the circular muscle to the agonist were only partly blocked. With the circular muscle, the differences related to internal and external perfusion were less marked than in the longitudinal muscle. However, unlike the latter, the circular layer was slightly more sensitive to drugs applied internally, in relation to pD2 values. It is suggested that the difference in pD2 values may be due to the removal of noradrenaline by the neuronal uptake process, whereas the difference in maximal effect is due to the inaccessibility of part of the receptor population when drugs are added through the lumen. PMID- 4041677 TI - Effects of H1-receptor blocking drugs on the frog sartorius neuromuscular junction. AB - The effects of H1-receptor blocking agents, pyrilamine, promethazine, and diphenhydramine, on the amplitude and time course of endplate potentials (e.p.ps) were studied in the sartorius muscles of frogs. H1-receptor blockers (10(-5)-10( 4) M) reduced the amplitude of e.p.ps recorded intracellularly without affecting the resting membrane potential. The acetylcholine potential was decreased by perfusion of H1-receptor blockers. However, when the muscle fibre was stimulated directly, threshold and magnitude of action potential were not affected by H1 receptor blockers. The time constant of decay of the e.p.ps recorded extracellularly was reduced by H1-receptor blockers and the decay remained exponential with a single time constant. The quantal content was not reduced by perfusion of H1-receptor blockers at a concentration of 10(-4) M. It is assumed that the major site of action of these H1-receptor blocking agents is at the postsynaptic membrane. PMID- 4041679 TI - Affinity and efficacy correlate with chemical structure more than potency does in a series of pentatomic cyclic muscarinic agonists. AB - The efficacy and affinity of nine pentatomic cyclic muscarinic agonists were determined on the guinea-pig ileum, according to the method of Furchgott & Bursztyn (1967). The efficacy and affinity of these agonists are affected differently by structural modifications. Our results suggest that a strong dipole oriented in the same direction as that of the hydroxy group of muscarine, or the presence of a polarizable atom in the same position, are important for efficacy. PMID- 4041678 TI - Potassium changes the relationship between receptor occupancy and the inotropic effect of cardiac glycosides in guinea-pig myocardium. AB - K+ (2.4-15.6 mmol l-1) antagonized the positive inotropic effect of dihydro ouabain. The concentration-effect curves became steeper with the shift to higher concentrations of the glycoside. At 1.2 mmol l-1 Ca2+, an increase in K+ from 2.4 to 12 mmol l-1 required tenfold higher concentrations of dihydro-ouabain to produce equal inotropic effects. This factor was reduced to four at 3.2 mmol l-1 Ca2+. The same change in K+ concentration, at 1.2 mmol l-1 Ca2+, diminished the inotropic effect of ouabain on rested-state contractions by a factor of six. The positive inotropic effect of Ca2+ was also antagonized by K+ (1.2-12 mmol l-1). Reduction of Na+ from 140 to 70 mmol l-1 abolished the antagonistic action of K+ (1.2-8.0 mmol l-1). Moreover the inotropic effect of Ca2+ was enhanced. Reduction of Na+, from 140 to 70 mmol l-1, antagonized the positive inotropic effect of dihydro-ouabain more at low (2.4 mmol l-1) than at high (8.0 mmol l-1) K+. Accordingly, the extent of the dihydro-ouabain-K+ antagonism was reduced. When the K+ concentration was increased from 2.4 to 12 mmol l-1, [3H]-ouabain binding was reduced by a factor of three. This is less than the reduction in the inotropic effectiveness of ouabain or dihydro-ouabain. Reduction of stimulation frequency from 1 to 0.1215 Hz did not significantly alter the antagonistic effect of K+. Diminution of Vmax of the action potential was observed only at K+ concentrations greater than 5.9 mmol l-1, whereas the resting membrane potential was continuously depolarized over the entire range of K+ concentrations. The results support the view that the reduction in receptor affinity cannot be the sole cause of the antagonism between the glycoside and K+. Impairment of passive Na+ influx during diastole, due to the K+-dependent depolarization of the resting membrane potential, contributed to about one half of the glycoside-K+ antagonism. PMID- 4041680 TI - Effect of nicotine on blood flow, oxygen consumption and glucose uptake in the canine small intestine. AB - Resting blood flow, arterio-venous glucose and oxygen (A-V)O2 differences, glucose uptake and oxygen consumption by a segment of the upper jejunum were measured in anaesthetized dogs. Systemic arterial pressure was also measured. The effect of nicotine infusion (25 micrograms kg-1 i.v., over 10 min) on these measurements was recorded in untreated dogs, in dogs treated with propranolol (0.5 mg kg-1) to produce beta-adrenoceptor blockade and in dogs after alpha 1 adrenoceptor blockade with prazosin (0.2 mg kg-1). Nicotine cause a significant pressor response during infusion and a hypotensive response during the post infusion period. Propranolol did not significantly affect these results. Jejunal blood flow increased in the first half of nicotine infusion in both the untreated and beta-blocked animals. Vascular resistance was reduced during nicotine infusion and the decrease persisted post infusion in the beta-blocked group. In the untreated group (A-V)O2 was significantly reduced during the first 5 min of nicotine infusion, thereafter it returned to control levels, then rose significantly above control level, post infusion. beta-Adrenoceptor blockade had little effect on these responses to nicotine. When oxygen consumption was calculated it was found that nicotine had little effect during or after infusion. Nicotine caused significant hyperglycaemia during and for about 1 h after infusion. Tissue release of glucose was occasionally observed following the infusion. beta-Adrenoceptor blockade reduced the hyperglycaemia caused by nicotine. beta-Blockade alone increased uptake and nicotine caused a further three to four fold increase. Prazosin abolished the effects that were observed in the untreated and the alpha-blocked animals. 6 The present findings, related to our previous observations on the effects of catecholamines on glucose uptake by the bowel, are consistent with the hypothesis that nicotine has its action on bowel glucose uptake or release through its well-established action in releasing catecholamines and in activating beta-adrenoceptors. The responses are not related to oxygen utilization. PMID- 4041682 TI - Pharmacological basis for the induction of gastric carcinoid tumours in the rat by loxtidine, an insurmountable histamine H2-receptor blocking drug. AB - The very late occurrence of gastric carcinoids in a life-span carcinogenicity study with loxtidine in the rat might have resulted from continuous achlorhydria induced by this long-acting unsurmountable histamine H2-antagonist. The nature of the anti-secretory activity of loxtidine was compared with that of ranitidine on histamine-induced acid secretion in the perfused stomach preparation of the rat and in the rat isolated gastric mucosa preparation. Ranitidine and loxtidine had qualitatively different inhibitory effects on acid secretion, ranitidine being a competitive antagonist of histamine even at high concentrations, whereas the effect of loxtidine on both preparations was unsurmountable at relatively low concentrations. These results support the hypothesis that the late formation of gastric carcinoids in rats receiving loxtidine is a consequence of persistent achlorhydria caused by unsurmountable blockade of parietal cell H2-receptors. PMID- 4041681 TI - Electrophysiological actions of nicotine on substantia nigra single units. AB - Extracellular recordings of single unit activity were made in the substantia nigra (SN) of chloral hydrate-anaesthetized rats. Dopaminergic neurones of the pars compacta (SNC) were stimulated by (-)-nicotine bitartrate (1.0 mg kg-1) given subcutaneously (s.c.). This action was prevented by the secondary amine mecamylamine HCl (2.0 mg kg-1 i.v.) but not by a ganglion-blocking dose of the bisquaternary compound chlorisondamine Cl (0.1 mg kg-1 i.v.). Mecamylamine reduced the spontaneous activity of dopaminergic neurones. Nicotine, when administered intravenously (2-128 micrograms kg-1 cumulative dose), also stimulated dopamine cells and this action was dose-related. Nicotine, administered intravenously, (2-128 micrograms kg-1 cumulative dose) markedly excited non-dopamine cells in the pars reticulata (SNR) in a dose-related manner. In rats pretreated with chlorisondamine (0.1 mg kg-1 i.v.), nicotine induced a small excitatory or depressant action, but the marked excitation was not seen. Mecamylamine (2 mg kg-1 i.v.) completely prevented the actions of nicotine. The results are consistent with a direct excitatory action of nicotine on dopaminergic neurones of the substantia nigra pars compacta. The pronounced excitatory action of systemically administered nicotine on non-dopamine cells of the pars reticulata appears to be of peripheral origin. PMID- 4041684 TI - Evidence that oxmetidine inhibits transmembrane-calcium flux in cardiac and vascular tissue. AB - Oxmetidine, at concentrations in excess of 1 X 10(-6)M, caused concentration dependent negative inotropic and chronotropic responses in guinea-pig isolated heart preparations. Oxmetidine, at concentrations in excess of 1 X 10(-5)M, caused negative inotropic responses in guinea-pig papillary muscle preparations. The negative inotropic responses to oxmetidine were associated with shortening of the plateau phase of the action potential. Verapamil and nifedipine caused similar shortening of the plateau phase of the action potential at equivalent negative inotropic concentrations indicating that oxmetidine may also act as a calcium antagonist. In preparations partially depolarized by raising extracellular K+ concentration, oxmetidine also exhibited negative inotropic activity and reduced the calcium-dependent action potential. However, unlike verapamil and nifedipine, oxmetidine did not show voltage-dependent activity. Oxmetidine, at concentrations in excess of 1 X 10(-5)M, inhibited Ca2+-dependent contractions of dog saphenous vein preparations and inhibited 45Ca2+-uptake into veins depolarized by high extracellular K+. In vivo, these calcium antagonist actions of oxmetidine were demonstrated by vasodilatation, reduction in blood pressure, bradycardia and reduced cardiac output in anaesthetized cats. Oxmetidine, at concentrations of 1 X 10(-5)M and above, shows properties consistent with inhibition of transmembrane Ca2+ flux. This action can be distinguished from other calcium antagonists as the effects of oxmetidine are not voltage-dependent. PMID- 4041683 TI - Enthalpy-entropy relationship in drug-cholinoceptor interaction: a new approach. AB - The partial molal volume at infinite dilution, V2, was determined in toluene, benzene and acetonitrile for fifteen different drug molecules comprising muscarinic agonists, partial agonists and antagonists. The difference in V2 between a given drug, X, and hyoscine, expressed as (V2x - V2h) was then multiplied by the internal pressure of the holding phase (Pi approximately cohesive energy density) in order to obtain an estimate of the excess enthalpy (delta H) over hyoscine in the interaction of drug molecule X with a common cholinoceptor. As a working hypothesis, delta H for hyoscine is taken as zero, hyoscine having the lowest V2/affinity ratio of any drug in the series investigated. The corresponding change in entropy (delta S) was then calculated from the relationship: RT ln Kx = Pi(V2x - V2h) - T delta S, where Kx is the affinity constant of drug molecule X to the common cholinoceptor, obtained independently. Linear regression of Pi (V2x - V2h) congruent to delta H from the data in acetonitrile over delta S gave a satisfactory isoequilibrium plot, r2 = 0.954, slope (beta) = 231 degrees K. The present approach offers a new course for the study of the enthalpy-entropy relationship in the interaction of drug molecules in a given series with a common receptor. It could provide an alternative to the Van't Hoff procedure for the estimation of relative delta H, and is independent of the free energy of binding (delta G). PMID- 4041685 TI - Genetic counselling for schizophrenia. AB - It is possible that genes contributing to the development of schizophrenia may be identified within the next decade. Genetic methods are improving rapidly, and are surrounded by great public interest. Requests for genetic counselling are keeping pace with this increased attention, but the problems faced by psychiatric genetic counsellors are complex, and the experience of offering such counselling and the issues involved are rarely discussed. In this context the paper describes a year's work counselling for schizophrenia in the Maudsley Hospital Genetic Clinic. PMID- 4041686 TI - Depression in general practice: case thresholds and diagnosis. AB - Using multiple diagnostic and epidemiological criteria, three samples of general practice (GP) depressives were studied: those prescribed a new course of antidepressants, those given other treatment, and those missed by the GP. The majority of patients qualified as psychiatric cases on the PSE Index of Definition, the Bedford College Criteria, and the Research Diagnostic Criteria. Most satisfied diagnostic criteria for depression, or (fewer) anxiety. The disorders were relatively mild and often borderline on all three systems. Depressives given other treatment most often failed to meet diagnostic criteria. About half the antidepressant treated patients received RDC diagnoses of major depression. Among the other treatment sample, only one-fifth met these criteria, and half had non-depressive diagnoses. Most cases of depression treated by GPs satisfy criteria for psychiatric disorder, but tend to be relatively mild and borderline in quality. PMID- 4041687 TI - Depression in general practice: clinical features and comparison with out patients. AB - General practice (GP) depressives prescribed an antidepressant were compared with those given other treatment, and with antidepressant-treated psychiatric out patient depressives. GP depressives were considerably less severely ill than out patients, with fewer depressive symptoms and shorter illness, as well as less primary and less endogenous depression. The two groups of GP depressives differed less, but those receiving other treatment tended to have less severe depression than those receiving antidepressants and were less likely to satisfy diagnostic criteria for depression. Depressives in GP differ considerably in clinical characteristics from psychiatric out-patient depressives, and clinical features influence the GP's decision to treat with antidepressants. PMID- 4041688 TI - Family management in the prevention of morbidity of schizophrenia: the adjustment of the family unit. AB - Changes in the functioning of family members were assessed during a randomly controlled study of community management of schizophrenia. Eighteen families who completed two years community management based upon behavioural family therapy were compared with 18 families who received patient oriented management with family support. Families receiving family management reported less disruption of activities, reductions in physical and mental health problems, and less subjective burden than those receiving the patient oriented approach. It is concluded that the benefits of family management extend beyond the reduction in clinical and social morbidity of the index patient to beneficial effects for the family as a whole. PMID- 4041689 TI - The pattern and prevalence of symptoms during the menstrual cycle. AB - One hundred volunteers completed a modified version of the Moos Menstrual Distress Questionnaire daily for 35 days. The purpose of the study was disguised. None of the participants was taking oral contraceptives. Significantly more symptoms were reported in the premenstrual and menstrual phases and fewer during the follicular phase of the cycle, but the pattern of response varied considerably between subjects. Symptom reporting was higher, in all phases of the cycle, in women with high trait anxiety or psychiatric morbidity (indexed by the General Health Questionnaire) but these measures did not relate to fluctuations of symptoms around the menstrual cycle. The need for prospective longitudinal studies of menstrual cycle symptomatology is emphasised. PMID- 4041690 TI - The role of meals as a reinforcing event in a token economy programme. AB - Items such as meals have frequently been used as back-up events in Token Economy Programmes (TEPs) because of their supposed reinforcing effectiveness. However, despite the dubious ethical questions that this raises, there is little research evidence to support the necessity for their use in TEP's with hospitalised chronic mentally ill patients. The effects of introducing meals as a 'free' item on patients' performance of a number of target behaviours were investigated in a TEP where they had previously been scheduled as a back-up event. While 'free' meals produced a slight increase in the actual number of meals eaten, there were no systematic effects on patients' performance of the target behaviours. PMID- 4041691 TI - Home care for chronic mental illness in Bangalore: an experiment in the prevention of repeated hospitalization. AB - The article describes the outcome of a comparative study of home care, by a trained nurse, versus hospital out-patient supervision in the management of chronic psychiatric patients in Bangalore, India. Twenty-five patients, with a mean duration of illness of nine years, were started on the home care programme while a matched control group of 25 similar patients continued the regular out patient contact offered by the hospital. Comparative assessments were carried out on the groups at the time of intake and again after two years. The results indicate that hospital admission was less often needed among the home care group. PMID- 4041692 TI - Ageing and affective disorders: the age at first onset of affective disorders in Scotland, 1969-1978. AB - First admission rates from 1969-78 for Scottish psychiatric units were calculated for discharge diagnoses of affective psychosis for each five-year age-group from 15 years to over 74 years. There were clear-cut linear increases in rates of depressive psychoses, mania, and all affective psychoses, consistent with a relatively steady increase in the rate of first-onset affective psychoses with increasing age. These findings are discussed in terms of social, psychological, and biological hypotheses of the causes of affective disorder. It is argued that no single factor could produce the observed linear increases with age and that the data appear more consistent with an integrative aetiological model of affective disorder. PMID- 4041693 TI - The bereaved child: variables influencing early psychopathology. AB - This is a 13-month follow-up study of 105 two to 17 year-old children bereaved of one parent, with 85 controls. Data were gathered on physical and mental health in the children and surviving parents, the child's sex and age and the bereaved parent's sex and psychopathology being included as risk factors. Dysphoria, falling school performance and withdrawn behaviour were significantly increased in bereaved children of both sexes at all ages, while temper tantrums, bedwetting and the depressive syndrome only increased in the age and sex categories normally associated with these conditions. A global index of psychopathology was increased compared with controls on most subgroups of bereaved children (P less than 0.0001), the highest scores for both sexes being associated with having a mentally ill (usually depressed) widowed mother. The results are discussed and suggestions made for future research. PMID- 4041694 TI - Notification of addicts and the medical practitioner: an evaluation of the system. PMID- 4041695 TI - Lycanthropy lives on. PMID- 4041696 TI - 1,250 electroconvulsive treatments without evidence of brain injury. PMID- 4041698 TI - Understanding the Italian experience. PMID- 4041697 TI - Results of investigations in 150 demented patients consecutively admitted to a psychiatric hospital. PMID- 4041699 TI - Lorazepam dependence and chronic psychosis. PMID- 4041700 TI - Dupuytren's disease and mental handicap. PMID- 4041701 TI - Season of birth of schizophrenics in Hong Kong. PMID- 4041702 TI - Cognitive science and behaviourism. AB - In this paper it is argued that cognitive scientists, claiming the support of brain science and computer simulation, have revived a traditional view that behaviour is initiated by an internal, autonomous mind. In doing so, they have misused the metaphor of storage and retrieval, given neurology a misleading assignment, frequently replaced controlled experimental conditions with mere descriptions of conditions and the assessment of behaviour with statements of expectations and intentions, given feelings and states of mind the status of causes of behaviour rather than the products of the causes, and failed to define many key terms in dimensions acceptable to science. PMID- 4041703 TI - The locus of the Stroop effect: one site masquerading as two? AB - Two experiments are reported, which used modifications to the normal Stroop task. Both required cued responses, the first being designed to eliminate interference at the output stage, and the second being an attempt to rule out interference before the output. In both cases interference effects persisted. The results are considered to support Seymour's (1977) account of overlapping conceptual codes. PMID- 4041704 TI - Orthographic and phonetic coding in developmental dyslexia. AB - Memory coding in dyslexic readers and reading-age-matched controls was investigated using cued recall. In the first phase of the experiment subjects made rhyme judgements about pairs of words. In the second phase one member of each pair (the cue) was used to cue recall of the other member of the pair (the target). Cues and targets were either rhyming and orthographically similar, rhyming and orthographically distinct, orthographically similar and not rhyming, or unrelated. Dyslexics were as accurate at detecting rhyme compared to the reading-age-matched controls; however, they were slower and were subject to a greater orthography effect (Seidenberg & Tanenhaus, 1979). Overall memory performance did not differ between the two groups. However, dyslexics were found to make more use of an orthographic code with both visual and auditory presentation. They made less use of a phonetic code in the visual but not the auditory condition. The results support the view that dyslexics have less easy access to a phonological code in memory, but they are able to compensate for this by increased use of a visual/orthographic code. PMID- 4041705 TI - Identity priming in the recognition of familiar faces. AB - Morton (1969) proposed that word recognition is mediated by logogens--threshold devices whose thresholds would be lowered after 'firing' and only slowly return to near their original levels. Extension and revision of the original logogen model has occurred in response to results obtained in experiments which examine the effect of previous exposure to an item on later recognition thresholds. On the basis of results obtained in such identity priming studies, Warren & Morton (1982) argued that picture recognition might be mediated by pictogens--threshold devices which respond when any picture of an object is seen. Warren & Morton found that recognition of a pictured object was facilitated by earlier exposure to the same or a different picture of the object, but was not facilitated by earlier exposure to the object's name. Recently, several authors have suggested that face recognition might be mediated by units somewhat analogous to logogens or pictogens. In order to explore this analogy, Warren & Morton's procedure of identity priming in picture recognition was adopted to examine identity priming in the recognition of famous faces. When the recognition test involved naming a celebrity's face, identity priming was obtained from prior exposure to the celebrity's name, a different picture or the same picture as that used in the test. If the procedure was modified so that subsequent recognition did not require retrieval of the name, a pattern consistent with the word and picture recognition literature was found. Prior exposure to either a different or the same picture produced a priming effect but prior exposure to the celebrity's name did not. These results are generally consistent with the hypothesis of face recognition units. Differences between face recognition units and pictogens are also discussed. PMID- 4041706 TI - Delinquent behaviour and attitudes to formal authority. AB - A scale was developed to assess attitudes towards formal authority in the school and in the public domain (police and law). Data derived from a sample of young adolescents (13 years) indicated that attitudes towards authority in these two domains were highly rated (r = 0.57, P less than 0.001). Factor analysis yielded four interpretable factors--alienation from the institutional system, belief in the absolute priority of rules, perception of the bias vs. impartiality of authorities, and personal relationship to school life--accounting for 47.6, 13.9, 9.3 and 8.0 per cent of common variance respectively. Both overall attitude scores and factor scores were significantly related to self-reported delinquencies. Finally, covariance analysis of the results indicated that the attitude variable accounted for a substantial proportion of the sex difference in delinquency. PMID- 4041707 TI - Predicting our own aggression: person, subculture or situation? AB - Using a self-report technique, teenaged subjects (stratified by sex and social class) were asked to report their predicted behaviour over 24 conflict scenarios involving 12 male and 12 female targets. In terms of degree of aggression predicted, there was a strong effect of situation. Towards male targets, lower middle-class subjects were more aggressive than upper middle-class subjects and males were more aggressive than females. With respect to female targets, the social class difference again appeared but there was no simple sex difference. The interaction of sex and social class indicated that lower middle-class females were most aggressive toward female targets. Cross-situational consistency was low even controlling for class and sex, indicating little support for a generalized 'aggressive personality'. The most powerful single effect was the situation being judged. Feature analysis of situations tending to produce fight vs. flight responses suggested that flight is associated with perceived high risk encounters whereas fighting is the modal response in 'fair fight' situations where the risk of injury is lower. It is suggested that impression management concerns operate only in these low risk situations. PMID- 4041708 TI - The effect of antiseptics on the healing wound: a study using the rabbit ear chamber. AB - The effects of several antiseptic agents on granulation tissue were studied using rabbit ear chambers as models of the healing wound. This enabled us to study dynamically the action of these agents on the microcirculation of the wound. All the agents tested caused some adverse effect, but in the cases of hypochlorite antiseptics Eusol and Chloramine T, blood flow in the capillary circulation of the granulation tissue ceased and the process of repair was subsequently delayed. A laser Doppler flowmeter was used to measure these changes in local perfusion which reflected the toxic effects seen on microscopy of the ear chamber. PMID- 4041709 TI - Influence of diabetes mellitus on operative risk. AB - In a retrospective study postoperative morbidity was compared between 224 patients with diabetes mellitus and 224 non-diabetic control patients matched with regard to operative procedure (major vascular, abdominal and acute surgery for hip fracture), sex, age, complicating cardiovascular disease and weight. Forty-six patients in each group had complications, without any trend towards specific morbidity in the diabetic group. Incidence of morbidity was similar in diabetic patients treated with insulin, oral antidiabetic agents or diet. Diabetic patients with complications had significantly (P less than 0.01) lower blood glucose pre- and postoperatively than those without complications. The risk of overlooking (type II error) a 25 per cent increase in complication rate in the diabetic patients was less than 10 per cent and the risk of overlooking a 50 per cent increase in morbidity less than 0.5 per cent. These results do not support the common belief that diabetes per se may increase surgical risk. PMID- 4041710 TI - Pancreatic resection for severe acute pancreatitis. AB - Non-operative management of acute necrotizing pancreatitis carries a mortality of up to 80 per cent. Over the last 6 years we have pursued an aggressive policy of intensive supportive therapy followed by pancreatic resection in those patients with this severe form of the disease. We have managed 15 patients in this way, 14 by subtotal pancreatic resection (usually body and tail of the gland) and one by total pancreatectomy; 7 had early overwhelming multi-system failure with a median of 4 positive prognostic factors whilst 8 were operated on later between 3 and 8 weeks (plus one at 32 weeks) and had varying clinical pictures. Eight patients had ischaemia of the transverse colon which was noted at operation in four, and presented postoperatively in the remainder. Re-operation was necessary in 13 patients to remove further slough or resect ischaemic bowel. Five patients (33 per cent) died between 10 days and 4 weeks postoperatively, death being due to sepsis and multi-system failure in four and a massive retroperitoneal haemorrhage in one. Of the ten survivors, four require insulin. Timely excision of necrotic pancreatic tissue combined with intensive supportive therapy may help reduce the high mortality in this condition. PMID- 4041711 TI - Conservative pancreatectomy. AB - By convention, resection of the proximal pancreas includes the distal stomach (and duodenum) and resection of the distal pancreas includes the spleen. In 28 patients the stomach and spleen were preserved to minimize functional disability. In 13 patients with proximal pancreatectomy (7 men, median age 39 years) the pylorus and first 3 cm of duodenum were preserved. Indications were chronic pancreatitis (n = 9) and localized neoplasia (ampulla 2, duodenum 1, insulinoma 1). One patient died (aged 81 years), and 2 required re-operation for a pancreatic abscess or stenosed choledochojejunostomy. The 12 survivors are well at a median of 1.25 years (range 0.25-3.25 years). In 15 patients with distal pancreatectomy (6 men, median age 44 years) the spleen was preserved. Indications were islet cell tumour in 2 and chronic abdominal pain in 13,9 of whom had an isolated dorsal pancreas and 6 of whom had histological evidence of chronic pancreatitis. Recovery was uneventful apart from 2 patients with a fluid collection in the lesser sac, 1 needing percutaneous aspiration. In the absence of gross inflammatory adherence, partial pancreatectomy need not entail removal of the adjacent stomach or spleen. PMID- 4041712 TI - Gastro-oesophageal reflux and oesophagitis before and after vagotomy for duodenal ulcer. AB - Fifty patients undergoing elective vagotomy for the treatment of chronic duodenal ulceration have been investigated pre-operatively and again 3 months postoperatively to determine the extent and severity of associated gastro oesophageal reflux. Pre-operatively all patients had a normal lower oesophageal sphincter pressure but 50 per cent had symptoms of gastro-oesophageal reflux, 42 per cent had excessive reflux on 24 h pH monitoring and 30 per cent had oesophagitis on endoscopy and/or oesophageal biopsy. Postoperatively, reflux symptoms were present in only 12 per cent of patients but pH studies were still abnormal in 36 per cent and oesophagitis was observed in 32 per cent. Lower oesophageal sphincter pressure was unaffected by vagotomy. Gastro-oesophageal reflux is common in pre-operative duodenal ulcer patients and is not significantly reduced by vagotomy. Careful pre-operative oesophageal assessment is necessary to determine which duodenal ulcer patients require an anti-reflux procedure in addition to vagotomy. PMID- 4041713 TI - Pyloric reconstruction. AB - Fourteen patients with persistent and severe postcibal symptoms following vagotomy and pyloroplasty for duodenal ulcer had the pylorus reconstructed. A dumping provocation test was useful in patient selection and evaluation of results. When assessed between 6 months and 3 years after operation, nine patients had an excellent or good result and three were improved. Surgical technique is relatively simple and the operation should be considered and practised more often than it seems to be from documented experience. PMID- 4041714 TI - Endoscopic management of upper urinary tract stones. AB - Since 1981, 525 renal and ureteric calculi have been removed with percutaneous nephrolithotomy (PCN) or transurethral ureteroscopy as the primary modalities of therapy. Successful extraction of the stone at the first attempt was achieved in 92 per cent of cases by PCN and 70 per cent of cases by ureteroscopy, whilst further endoscopic surgery improved the overall success rates to 98 per cent and to 80 per cent respectively. Complication rates from these procedures have both been low as has the morbidity, with most patients leaving hospital within 4 days and returning to work within 2 weeks. The successful development of endoscopic lithotomy and the use of in situ destruction techniques has meant that we now reserve open surgery for difficult multibranched staghorn calculi and ureteric stones embedded in the urothelium. With the advent of extracorporeally generated shockwave lithotripsy it is likely that even these types of stone will be amenable to minimally invasive procedures. PMID- 4041715 TI - Use of a ringed intraluminal graft in the operative management of abdominal aortic aneurysms. AB - The efficacy of a non-sutured technique of anastomosis has been assessed in 20 patients who had bifurcated grafts inserted for aneurysms of the infrarenal aorta. The grafts had rigid Dacron-covered metal rings incorporated at each end and the anastomoses were effected by securing these rings within the lumen of the vessel with a firmly tied Dacron tape. In order to allow access of the ring to the lumen of the aorta it was necessary to employ an intraluminal occlusion balloon catheter for proximal control. The patients included in the study formed a particularly high risk group. There were 12 emergency and 8 elective procedures. The mean duration of the operations was 134 +/- 34 min (+/- s.d.); the mean blood loss during surgery was 3498 +/- 2660 ml (+/- s.d.) and the mean length of inpatient stay after operation was 16 +/- 13 days (+/- s.d.). There were eight postoperative deaths and post-mortem examination, which was allowed in six cases, showed satisfactory appearances of the grafts and anastomoses. The surviving patients have remained free from complications for up to 18 months after operation. A non-sutured technique is possible for most aortic anastomoses but is of limited applicability for iliac and more distal anastomoses. With further technical refinements an intraluminal graft with a non-sutured aortic anastomosis may become a valuable alternative to the conventionally sutured prosthesis in the management of ruptured abdominal aneurysms. PMID- 4041716 TI - The influence of tumour cell DNA abnormalities on survival in colorectal cancer. AB - The cellular DNA content was measured from paraffin-embedded material in 134 colorectal cancers from patients in whom the outcome was known. Seventy-two (55 per cent) were found to contain cells with abnormal DNA (DNA aneuploid). The presence of such a population of cells was not related to pathological stage or histological grade. However, only 14 (19 per cent) patients with DNA aneuploid tumours survived 5 years compared with 27 (43 per cent) of patients with diploid tumours (chi 2 = 8.0, P = 0.005). Stepwise logistic analysis showed cellular DNA content to be an important prognostic factor in colorectal cancer, independent of pathological stage and histological grade. PMID- 4041717 TI - Hypovolaemia and healing in colonic anastomoses. AB - Colonic anastomotic leakage is more common following emergency resections than after elective operations. Transient hypovolaemia, which is more likely to occur during emergency surgery, has been shown to impair collagen metabolism in abdominal and skin wounds but its effect on colonic anastomotic healing has not been previously examined. Acute intra-operative loss of 10 per cent circulating blood volume in rats significantly impaired collagen concentration in both ileocolic (P less than 0.02) and colocolic (P less than 0.05) anastomoses measured on the third postoperative day. This degree of blood loss did not significantly affect early anastomotic strength. Hypovolaemia leads to tissue hypoxia, and this in turn may lead to impaired anastomotic healing. Measurement of tissue oxygen tension may predict poor healing by identifying inadequate intestinal perfusion. Colonic pTO2 measured in rabbits was significantly lower than in small bowel (37 +/- 18 mmHg versus 42 +/- 18 mmHg; P less than 0.001), and fell significantly in colon following 10 per cent blood loss (P less than 0.001). We conclude that adequate intra-operative fluid replacement during colonic resection and anastomosis is a prerequisite for successful healing. PMID- 4041718 TI - Fibro-adenoma of the breast. AB - A retrospective study of 134 patients with a clinical diagnosis of fibro-adenoma of the breast indicated that histological confirmation of this diagnosis is made in only 50 per cent. The majority of the others have a diagnosis of benign mammary dysplasia. Eight patients had an unsuspected carcinoma, all but one being above the mean age for the fibro-adenoma group. The natural history of fibro adenoma is not known precisely. In view of the high sensitivity of fine needle aspiration cytology in the diagnosis of malignant disease, we believe that there is justification to carry out a prospective study to determine this. In this study women with a clinical diagnosis of fibro-adenoma will be carefully observed provided they are less than 35 years of age and fine-needle aspiration cytology reveals no malignant cells. PMID- 4041719 TI - Accuracy of aspiration cytology in the diagnosis of breast disease. AB - The accuracy of fine needle aspiration cytology has been assessed in 480 consecutive breast lesions where definitive histology was later available. The results in terms of specificity and sensitivity have also been compared to mammography and clinical examination. With adequate smears aspiration cytology was 100 per cent specific with no false positive diagnosis. This compares with 15 false positive mammograms and 12 false positive diagnoses on clinical examination. Cytology was unsatisfactory in 36 per cent of benign lesions owing to poor cellularity of the sample but when considered with mammography and examination led to a reduction in biopsies for benign disease. A definitive cytological diagnosis of malignant tumours resulted in a reduction in frozen sections with a substantial saving of resources and improvement in patient counselling. No mastectomy was performed for benign disease. PMID- 4041721 TI - Choledochoduodenostomy and the blind loop syndrome. PMID- 4041720 TI - Are the lesions of duct ectasia sterile? AB - A prospective study was established to determine whether, using suitable transport media, bacteria could be isolated from the lesions of mammary duct ectasia. The results indicate that both aerobic and anaerobic organisms are present in a high proportion of patients with nipple discharge associated with this condition and in all patients who develop peri-areolar sepsis (abscess and mammillary fistulae) as part of the syndrome. The lesions of duct ectasia are therefore not sterile and the possibility exists that bacteria have a role in the aetiology and pathogenesis of this condition. PMID- 4041722 TI - Peritoneal lavage in severe acute pancreatitis. PMID- 4041723 TI - Evolving practice in acute diverticulitis. PMID- 4041724 TI - Long-term results after pancreas resection for acute necrotizing pancreatitis. AB - This study was designed to investigate the long-term effects of early pancreatic resection for acute necrotizing pancreatitis. During 1973-1978 40 resections were performed in our clinic. Eleven patients died initially (28 per cent). None of the four further deaths was due to pancreatitis or associated disorders. Twenty four patients were re-examined 5-11 years after resection--one patient refused to participate. Five had not been able to return to work because of severe polyneuropathy; one more had retired because of chronic pancreatitis in the pancreatic remnant. Polyneuropathy was found in five further patients. The reason for this high incidence of polyneuropathy (42 per cent) remains unknown. Eight patients still drank excessive alcohol; three of them had had recurrent pancreatitis and dyspepsia, and insulin requiring diabetes. All but 2 (92 per cent) had diabetes, 14 needing insulin--half of them at 6 months to 6 years after the resection. Moreover, 11 patients (46 per cent) suffered from dyspeptic symptoms. The results suggest that because of the high frequency of late complications, in addition to the early complications, early resection of pancreas should be critically re-evaluated as the treatment for acute necrotizing pancreatitis. If resection is used in patients with extreme pancreatic necrosis, careful and continuous postoperative follow-up will be needed. PMID- 4041725 TI - Changes in colonic motility during the development of chronic large bowel obstruction. AB - The effect of chronic progressive distal large bowel obstruction on colonic motility was studied in six mini-pigs. Motility was detected in vivo during the development of obstruction with chronically implanted Ag/AgCl electrodes using an impedance technique. When the obstruction was complete the segments of bowel were resected and spontaneous contractile activity and response to cholinergic stimulation were studied in an organ bath. Any hypermotility resulting from obstruction was shortlived and a gradual state of hypomotility supervened proximal to the obstruction. Decompression of the bowel did not result in the immediate return of motility and the resected bowel was unresponsive to carbachol. These results suggest that spontaneous resolution of large bowel obstruction is unlikely and that motility disturbances are unlikely to be a cause of anastomotic dehiscence. PMID- 4041726 TI - Spontaneous bleeding into a parathyroid cyst. PMID- 4041727 TI - The role of surgical local excision in the treatment of rectal cancer. AB - Selection of patients with ulcerating rectal cancer for treatment by local excision has been governed by a policy based on clinical and histological criteria; if these criteria are not fulfilled, major resection is recommended. This policy was re-examined in three groups of patients treated by local excision: Group 1 for cure (27 patients), Group 2 due to unfitness for major surgery (13 patients), Group 3 for local tumour control in the presence of metastatic disease (6 patients). When the policy was fulfilled, there was a cancer-specific death rate of 8.3 per cent in Group 1 (two patients with poorly differentiated tumours) and 0 per cent in Group 2. Unavoidable policy breaches occurred when patients refused major surgery or were too unfit: in the latter elderly group, this did not have the adverse effect expected. It is concluded that pre-operative clinical digital assessment and histological grading are a satisfactory means of identifying a small group of tumours appropriate for local treatment and that the results justify local excision where the policy is observed. PMID- 4041728 TI - A multivariate analysis of clinical and pathological variables in prognosis after resection of large bowel cancer. AB - Data on 709 patients who had a resection for colorectal carcinoma at Concord Hospital between 1971 and 1980 were studied to determine the independent effects on survival of several patient characteristics and pathological variables using the Cox regression model. Clinicopathological stage had the strongest association. Other variables ranked according to their relative importance independent of stage were: histological grade, level of direct spread, the presence of venous invasion, age and sex of the patient and the presence of obstruction. PMID- 4041729 TI - Immediate resection in emergency large bowel surgery: a 7 year audit. AB - In a consecutive series of 153 emergency admissions with large bowel disease during a 7 year period, 49 per cent were for colonic obstruction, 46 per cent for peritonitis and 5 per cent for miscellaneous conditions. Urgent operation was performed on 104 (68 per cent) patients. Of those operated upon, 82 (79 per cent) had a primary resection with a mortality rate of 12.2 per cent, intraperitoneal sepsis rate of 2.4 per cent and wound sepsis rate of 7.3 per cent. The median postoperative hospital stay was 21 days. An immediate anastomosis was performed in 46 (56 per cent) patients with a mortality rate of 8.7 per cent, anastomotic leak rate of 2.2 per cent, and wound sepsis rate of 8.7 per cent. The median postoperative hospital stay was 19 days. The mortality in patients presenting with large bowel emergencies is related to age and advanced malignant disease. Immediate resection is applicable in over 80 per cent of patients requiring urgent operation and morbidity can be low and treatment economical. Immediate anastomosis after proximal colonic resection is safe and the use of intra operative colonic irrigation permits a primary anastomosis in selected patients after emergency resection of the distal colon. PMID- 4041730 TI - Intra-operative colonic irrigation in the management of left-sided large bowel emergencies. AB - In a consecutive series of 93 patients who required emergency surgery for distal colonic lesions, 61 had primary bowel resection with immediate anastomosis after intra-operative antegrade colonic irrigation. The operative mortality was 8 per cent, anastomotic leakage rate 7 per cent and superficial wound infection occurred in 3 per cent of patients. The mean hospital stay was 13 days. Of the remaining 32 patients, 3 did not have a resection and 29 had a primary resection and end colostomy without anastomosis: bowel continuity was later restored in 17 of 28 survivors (61 per cent) but 11 (39 per cent) were left with a permanent colostomy. The hospital mortality in this group was 6 per cent, superficial wound infection rate 14 per cent and the mean hospital stay 26 days. The results of this study suggest that intra-operative colonic irrigation is an effective method enabling the surgeon to perform a primary anastomosis with reasonable safety after emergency resection of selected distal colonic lesions. PMID- 4041731 TI - Retrieval of an unusual foreign body from the second part of the duodenum. PMID- 4041732 TI - The results of surgery for epidermoid carcinoma of the anus. AB - A series of 89 cases of anal carcinoma presenting over a 20-year period is reviewed. The majority were epidermoid carcinomas, 57 arising in the anal canal and 13 at the anal margin. The remainder were melanomas and basal cell carcinomas, and these were not considered further. The main presenting symptoms of epidermoid anal carcinomas were bleeding and pain. Tumours arising in the anal canal were commoner in women whilst those at the margin were more frequent in men. The majority (51/70) had a clinical diagnosis of malignancy made but in 19 cases this was not considered initially. The necessity for routine early histological diagnosis is stressed. Treatment was mainly surgical, either abdominoperineal resection (37 canal, 2 margin) or wide excision (8 canal, 11 margin). The 5 year survival of patients with anal margin tumours was better than those with canal lesions (50 per cent compared with 36 per cent). PMID- 4041733 TI - Patterns of flap recurrence following mastectomy. AB - Flap recurrence after mastectomy is divisible into three distinct entities: spot recurrence, multiple spot recurrence and field change. Spot recurrence and multiple spot recurrence are usually controlled by local measures and are not associated with any particular characteristics of the primary tumour. The field change type of flap recurrence is difficult to control and is associated with aggressive primary tumours (grade III, node positive, oestrogen receptor negative) and a very poor prognosis. The appearance of field change type of flap recurrence is an indication for systemic therapy. PMID- 4041734 TI - Sigmoid exclusion: a new technique in the management of radiation-induced fistula. AB - Colovesical and colovaginal fistulas following irradiation for pelvic malignancy represent a formidable surgical problem. Although complex surgical procedures to close the fistulas and restore continence have been described, often a defunctioning colostomy with an associated urinary conduit is the only feasible option. Three patients who have successfully undergone an original procedure (sigmoid exclusion) are presented. Sigmoid exclusion restores continence but avoids a permanent stoma. The involved sigmoid colon was isolated on its mesentery ensuring that the area incorporating the fistulas was not disrupted. The ends of the isolated sigmoid colon were closed and bowel continuity then restored by a colorectal or colo-anal anastomosis. Following closure of a temporary colostomy the patients were continent with no ill effects or sepsis from the excluded colon. This procedure has the dual advantage of restoring continence yet avoiding both an urinary conduit and a permanent colostomy, and represents a useful advance in the surgical management of radiation induced colonic fistulas. PMID- 4041735 TI - Congenital diaphragmatic hernia: a 20 year experience. AB - The records of 253 children with congenital diaphragmatic hernia admitted to The Hospital for Sick Children, Great Ormond Street, between 1961 and 1980 were analysed. The overall mortality of 37 per cent is greater than that reported in the preceding 13 years from the same institution, and showed no improvement over the 20 years. While there was no significant increase in the number of admissions over the study period, the proportion of children who underwent surgery within the first 6 h of life steadily increased from 13 per cent in the first five years to 39 per cent in the last five years. The mortality of this group (65 per cent) did not improve over the study period and this would account for the lack of improvement in the overall survival figures. However, analysis of birth weights, onset and severity of signs and lung weights indicates that the increasing number of early admissions was due to speedier transfer rather than to referral of more severely affected children in the later years. PMID- 4041736 TI - Maydl's hernia: report of a series of seven cases and review of the literature. AB - Seven cases of Maydl's herniae with two patients needing resection of bowel are presented. This condition is rare and may be lethal if unrecognized. The hernial sac contains two loops of bowel with another loop of bowel being intra-abdominal. The intra-abdominal loop of bowel may become strangulated, either alone or in combination with bowel in the hernial sac. It is more often seen in men, and predominantly on the right side. Maydl's hernia should be suspected in patients with large incarcerated herniae and in patients with evidence of intra-abdominal strangulation or peritonitis. Postural or manual reduction of the hernia is contra-indicated as it may result in non-viable bowel being missed. PMID- 4041737 TI - Cholecystohepaticodochal fistula: the value of pre-operative recognition. PMID- 4041738 TI - Haematuria after blunt trauma: the role of pyelography. AB - This study is a combined prospective and retrospective review of 208 patients presenting with haematuria after blunt abdominal trauma. One hundred and twelve patients had an urgent intravenous pyelogram (IVP) with cystogram performed, while the remaining ninety-six were observed with serial urinalysis without any further investigation. Nineteen of the twenty-three patients with a positive IVP had gross haematuria and the remaining four had microscopic haematuria. Twenty two of the patients with an abnormal IVP had positive abdominal signs, whilst only one case (with severe head injury) had no abdominal signs. In the 96 cases who were observed without IVP no complications occurred. It is suggested that if certain clinical criteria are observed most patients with post-traumatic microscopic haematuria can safely be spared an IVP. Indications for emergency IVP should include: gross haematuria or microscopic haematuria associated with abdominal signs or severe head injury or fracture of pelvis or spine. Had these criteria been observed during this study, 130 patients (62 per cent) would have avoided the risks and expenses of an IVP, and no significant urological injury would have been missed. PMID- 4041739 TI - Intramuscular haemangioma of the extremities: is computerized tomography useful? AB - Fourteen patients with intramuscular haemangiomas of the extremities were included in the study. All had computerized tomography (CT) and thirteen had angiography. Twelve of the thirteen were operated upon. CT scan proved to be an extremely valuable tool in the pre-operative planning as the extent of the lesion could be assessed accurately by this method; in most cases this was not possible with angiography. PMID- 4041740 TI - Peripheral resistance measurement in the assessment of severe peripheral vascular disease. AB - Thirty-seven patients undergoing femoropopliteal, fifteen undergoing femorodistal reconstruction and seven below knee amputees were subjected to prospective measurement of peripheral resistance. Resistance was significantly higher in the amputation and femorodistal groups than in the femoropopliteal group (P less than 0.03 and P less than 0.005 at 76 ml/min). In the femoropopliteal group patients with three vessel runoff had a significantly lower resistance than those with two or single vessel runoff (P less than 0.01). In the femoropopliteal group resistance of patent grafts at four months was significantly less than thrombosed grafts (P less than 0.006). Patients with a resistance less than 1200 mPRU had a significantly better patency than those in whom the resistance was greater than 1200 mPRU (P less than 0.05). Taking all the failed grafts there was a significant correlation between graft patency and resistance (P less than 0.003). Resistance measurement has been shown to correlate with the severity of the disease, with runoff defined radiographically and with graft patency. In a simplified form it may prove a useful adjunct to other methods of assessment in patients with distal disease. PMID- 4041741 TI - Internal iliac aneurysm and arteriovenous fistula presenting with pulmonary embolism. PMID- 4041742 TI - Aorto-enteric fistula caused by an atheromatous plaque penetrating a Dacron graft. PMID- 4041743 TI - Cystic adventitial disease of the common femoral and popliteal arteries. AB - Cystic adventitial arterial disease (CAAD) is usually situated in the popliteal artery and is a well recognized cause of intermittent claudication in otherwise healthy, young, non-smokers. Three cases of CAAD have recently been encountered, involving the popliteal artery in two patients and the common femoral in one. Two of these patients were hypertensive smokers in their sixth decades and only one was an otherwise healthy non-smoker, but all three had a characteristically rapid onset of symptoms. All had angiographic appearances suggestive of CAAD, confirmed by ultrasound and CAT scanning in one patient. Two were treated by resection of the affected artery and a replacement graft, both with excellent results. One popliteal lesion was bypassed with a vein graft which occluded after 3 months. CAAD may occur more commonly than generally realized. It can present in patients whose condition suggests an atheromatous cause for their symptoms. Since good results can be expected from appropriate surgical treatment in most cases, CAAD should be considered in the diagnosis of all patients with claudication, particularly when the onset has been rapid. PMID- 4041744 TI - Xanthogranulomatous pyelonephritis associated with pyeloduodenal fistula. PMID- 4041745 TI - Spontaneous oesophageal rupture. PMID- 4041746 TI - Risks of biliary surgery in the elderly. PMID- 4041747 TI - Circulating levels of fibronectin in surgical patients. PMID- 4041748 TI - Frontiers in colorectal disease. St. Mark's Hospital 150th anniversary international conference supplement. PMID- 4041749 TI - Megacolon in adults. PMID- 4041750 TI - Continuing experience with single layer appositional anastomosis in the large bowel. AB - Results of continuing experience with single layer appositional anastomosis of the large bowel during 8 years (1977-84) were extracted from a prospective computerized audit of all abdominal operations under one consultant. After 204 elective operations mortality rate was 1.5 per cent: there were no deaths from anastomotic leakage. The total incidence of wound infection (including late infections) was 2.0 percent. The median duration of postoperative stay was 9.7 days and the mode 8 days. Three clinical anastomotic leaks (total incidence 1.5 per cent) occurred in 140 patients (2.1 per cent) after elective colorectal anastomoses. A restorative anastomosis was made in 86 per cent of patients with rectal carcinoma 6-12 cm from the anus and in 29 per cent with tumours below 6 cm. The overall incidence of a permanent stoma for rectosigmoid carcinoma was 19 per cent. 'Protective colostomy' and anastomotic drains were not used. The safety and applicability of single layer anastomosis in the rectum are compared with those of stapling. PMID- 4041752 TI - Risk factors in childbirth causing damage to the pelvic floor innervation. PMID- 4041751 TI - Evacuation proctography in obstructed defaecation and rectal intussusception. AB - The symptoms of obstructed defaecation may present as a number of different syndromes including descending perineum, solitary rectal ulcer, irritable bowel and mucosal or complete rectal prolapse. In order to clarify the pathophysiology of obstructed defaecation we carried out dynamic and static radiological investigations together with manometric and electrophysiological measurements in ten patients with severe, intractable obstructed defaecation. Results were compared with a total of 35 control subjects. There were no significant differences in sphincter pressures or the recto-anal inhibitory reflex between patients and controls. Mean motor unit potential duration was prolonged in patients compared with controls (P less than 0.02) in the puborectalis and external sphincter indicative of neuropathic changes. X-ray measurements of the anorectal angle and perineal descent at rest showed no differences. However, obstructed defaecation patients had a greater increase in anorectal angle on straining (P less than 0.02) and significantly more descent on straining (P less than 0.002). Fast film sequence evacuation proctography showed that the anal canal was occluded by anterior rectal wall in four patients and five patients had variants of recto-rectal intussusception without overt rectal prolapse, which explained the obstructive symptoms. This information should allow the surgeon to follow a rational treatment programme based on the anatomical abnormality. PMID- 4041753 TI - Results of postanal repair: a retrospective study. PMID- 4041754 TI - Sphincter injuries: indications for, and results of sphincter repair. PMID- 4041755 TI - Gracilis muscle transposition for anal incontinence: late results. PMID- 4041756 TI - Magnitude of risk for cancer in patients with colorectal adenomas. PMID- 4041757 TI - Polyp follow-up: how, who for and how often? PMID- 4041758 TI - Follow-up after removal of colorectal adenomas and radical surgery for colorectal carcinomas. PMID- 4041759 TI - The rectum in adenomatous polyposis: the St. Mark's policy. PMID- 4041760 TI - Familial polyposis. PMID- 4041761 TI - Clinicopathological staging of colorectal cancer: has the time arrived? PMID- 4041762 TI - Clinical local staging of rectal cancer. PMID- 4041763 TI - Histological criteria for local excision. PMID- 4041764 TI - Indications for local excision of rectal cancer. PMID- 4041765 TI - Techniques of local surgical excision for rectal carcinoma. PMID- 4041766 TI - The feasibility of large scale population screening. PMID- 4041767 TI - Ileorectal anastomosis. PMID- 4041768 TI - Restorative proctocolectomy with ileal reservoir. PMID- 4041769 TI - Ileal 'J' pouch-anal anastomosis. PMID- 4041770 TI - Dysplasia and cancer in inflammatory bowel disease. PMID- 4041771 TI - Crohn's disease in young people. PMID- 4041772 TI - The management of internal fistulae in Crohn's disease. PMID- 4041773 TI - Anal lesions in Crohn's disease. PMID- 4041774 TI - Migraine coma. Meningitic migraine with cerebral oedema associated with a new form of autosomal dominant cerebellar ataxia. AB - A family with hemiplegic migraine has been documented for a period of over forty years. From this study and the literature we conclude that (1) migraine is a cause of recurrent coma which may be associated with life-threatening cerebral hemisphere oedema; (2) hyperpyrexia with CSF pleocytosis occurs in hemiplegic migraine, which may thus simulate viral meningoencephalitis; and (3) cerebral angiography is hazardous in hemiplegic migraine and may exacerbate coma and cerebral oedema. In the family reported, cerebellar ataxia was present during recovery from attacks of hemiplegic migraine and affected patients ultimately suffered from persistent ataxia with radiological cerebellar atrophy. This syndrome thus constitutes a distinct form of late-onset autosomal dominant cerebellar ataxia and also of familial periodic ataxia. The status of 'cerebellar migraine' is reviewed. PMID- 4041776 TI - Pathophysiology of blepharospasm and oromandibular dystonia. AB - The pathophysiology of reflexes mediated by the fifth and seventh cranial nerves has been studied in 16 patients with blepharospasm and oromandibular dystonia compared with normal age-matched subjects. The EMG activity of the dystonic spasms in the periocular and jaw muscles was similar to that described in other muscles in patients with generalized torsion dystonia. The latency of the R1 and R2 components of the blink reflex and of the corneal reflex was normal. However, the amplitude and the duration of the R1 and R2 and the duration of the corneal reflex were increased. In some patients the R1 component was also present on the side contralateral to the stimulus, while in normal subjects it was present only on the ipsilateral side. The excitability cycle of recovery of the R2 component of the blink reflex after a prior conditioning shock was enhanced in the patients. There were no EEG potentials preceding blepharospasms in the patients, although a Bereitschaftspotential was seen beginning some 500 ms prior to voluntary blinks in the same individuals. Exteroceptive suppression in the contracting masseter and orbicularis oculi muscles was absent in 40 to 50 per cent of the patients. The jaw jerk was present in all the patients with normal latency. These results indicate that the neuronal arcs of the facial reflexes in blepharospasm and oromandibular dystonia are normal. However, there is an abnormal excitatory drive, perhaps from the basal ganglia, to the facial motoneurons and the interneurons which mediate the facial reflexes in the brainstem. PMID- 4041775 TI - Impairment of olfactory recognition after closed head injury. AB - To investigate the effects of closed head injury (CHI) on olfactory identification, we administered a test of olfactory naming and forced choice recognition to 52 CHI patients who had no evidence of anosmia. The Olfactory Identification Test consisted of 'scratch and sniff' labels of familiar nonirritant odorants. In comparison with a normal control group (n = 19) of similar age, olfactory naming and recognition were impaired in the CHI series, particularly in patients with moderate or severe head injury. The presence of a haematoma or contusion in the frontal/temporal region was also related to impaired olfactory recognition. We suggest that nonmissile head injury can produce at least a partial impairment of olfactory recognition despite relatively preserved olfactory detection. PMID- 4041777 TI - Temporal frequency discrimination in optic neuritis and multiple sclerosis. AB - The temporal contrast sensitivity function and temporal frequency discrimination have been studied in normals and in 7 cases of multiple sclerosis or optic neuritis. Sinusoidal gratings of two spatial frequencies (0.2 and 2.0 cycles/deg) were used. The abnormalities demonstrated in the patients varied between individuals but overall a picture has emerged of four principal anomalies. The temporal transfer function of the 2 cycles/deg medium spatial frequency grating has a band-pass appearance, whereas it is low-pass in normal subjects (5 out of 8 eyes). The peak of temporal frequency discrimination function (i.e. the temporal frequency at which discrimination is most acute) occurs at a lower temporal frequency in the patients than in normal subjects particularly at the higher spatial frequency (5 out of 8 eyes for a spatial frequency of 2.0 cycles/deg; 2 out of 8 eyes for a spatial frequency of 0.2 cycles/deg). It was found that normal subjects were able to discriminate between the maximum temporal frequency used as a standard in the discrimination experiments (16 Hz) and a higher temporal frequency. In the patients, however, a cut-off in the discrimination function occurred at a temporal frequency well below this (8 out of 8 eyes for a spatial frequency of 2.0 cycles/deg; 2 out of 8 eyes for a spatial frequency of 0.2 cycles/deg). Further to the above result, in a number of patients an attempt was made to ascertain how the gratings were perceived in this abnormally extensive region of ambiguity in the high temporal frequency range. It was found that high temporal frequencies, at a constant contrast level above threshold and constant apparent contrast, were perceived either as flickering at a slower rate than did an intermediate temporal frequency or even appeared stationary. This effect was rare at the lower spatial frequency (1 out of 8 eyes) but was demonstrated in 4 out of 8 eyes at the spatial frequency of 2.0 cycles/deg. It was not specifically sought in all individuals. These results are discussed in the context of an information channelling model of temporal frequency processing in the visual system. PMID- 4041778 TI - Aphasia and handedness in relation to hemispheric side, age at injury and severity of cerebral lesion during childhood. AB - The effects of the variables of hemispheric side of lesion, age at injury and severity of cerebral damage on language performance and hand dominance were investigated in groups of hemiparetic children. Severity of cerebral damage was defined by the degree of structural abnormality shown on computed tomography (CT) scans. Tests of auditory verbal comprehension and object naming were used as indicators of productive and receptive language skills. The responses to a series of questions on a handedness inventory provided a rated measure of hand dominance. The results indicated that language deficits characterize the performance of all patient groups with left cerebral injuries. Impairments are more profound, however, in the case of left hemisphere injuries acquired after the age of 5 years. In addition, prenatal and early postnatal left cerebral lesions consistently result in strong sinistrality. It is concluded that the crucial variable underlying the demonstration of language deficits and left hand dominance is not severity of lesion but age at injury and hemispheric side of lesion. PMID- 4041779 TI - Effect of paraventricular nucleus lesions on arterial pressure and heart rate after aortic baroreceptor denervation in the rat. AB - Two series of experiments were done in male Wistar rats to investigate the effects of lesions of the paraventricular nucleus of the hypothalamus (PVH) on the maintenance and development of the elevated arterial pressure resulting from denervation of aortic baroreceptors. In the first series, after control recordings of arterial pressure (AP) and heart rate (HR), rats were subjected to either bilateral aortic depressor nerve (ADN) transection or sham-ADN transection. These animals were later subjected to either bilateral lesions of the PVH or sham-PVH lesions. AP (146 +/- 2 mm Hg) and HR (515 +/- 5 bpm) were significantly elevated in only the ADN-transected groups. Bilateral lesions of the PVH significantly reduced AP (119 +/- 3 mm Hg) and HR (440 +/- 8 bpm) in the ADN transected animals compared to ADN-transected sham-PVH-lesioned animals, to levels which were not significantly different from pre-ADN-transected levels (AP, 113 +/- 2 mm Hg; HR, 448 +/- 3 bpm), and from sham-ADN-transected PVH-lesioned (AP, 119 +/- 2 mm Hg; HR, 391 +/- 6 bpm) and sham-ADN-transected sham-PVH lesioned animals (AP, 116 +/- 2 mm Hg; HR, 436 +/- 4 bpm). In the second series of experiments, after control AP and HR recordings rats were first subjected to either bilateral lesions of the PVH or sham-PVH lesions, and second to either bilateral ADN transection or sham-ADN transection. PVH lesions did not significantly alter the AP and HR from control levels.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4041780 TI - Simultaneous recordings from pairs of cat somatosensory cortical neurons with overlapping peripheral receptive fields. AB - Fifty-three cell pairs in the somatosensory cerebral cortex were examined in pentobarbital-anesthetized cats for evidence of short latency interactions. Many neuronal pairs separated by distances of 150 to 500 micron were observed to have temporal dependencies. In a subset of 19 pairs where the surrounding multiunit activity could be classified as rapidly adapting or slowly adapting, short latency interactions existed only between cell pairs sharing the same multiunit background activity. If one member of the pair was in a slowly adapting background and the other in a rapidly adapting background, the cells did not influence one another. This observation was taken as evidence for parallel and separate processing of afferent signals from rapidly and slowly adapting cutaneous mechanoreceptors in cat somatosensory cortex. PMID- 4041781 TI - Genetic brain polypeptide variants in inbred mice and in mouse strains with high and low sensitivity to alcohol. AB - Twelve genetically determined brain polypeptide charge variants were identified by comparing cerebellar vermis of 7 inbred mouse strains and of mice selectively bred from 8 strains closely related to these 7 ancestral strains and one other for acute behavioral sensitivity to the sedative effects of ethanol. The selectively bred ethanol-sensitive (LS, long sleep) and insensitive (SS, short sleep) mice exhibited different allelic variants at 6 of these 12 gene loci expressed in the cerebellum. Variant polypeptide A1 (81 kdalton, pI 5.6) was shown to be associated with the membrane of synaptosomal mitochondria and to exhibit a basic variant in SS mice that is determined by a dominant allele. Other variant polypeptides showed codominant inheritance in F1 crosses. However, the phenotype of no single one of these brain polypeptides consistently correlated with the ethanol behavioral sensitivity of the 7 inbred mouse strains nor of 8 recombinant inbred (B X D, C57BL X DBA) strains. This finding supports the hypothesis that a substantial amount of inbreeding, leading to random fixation of alleles independent of selection for ethanol sensitivity, occurred during the breeding of the SS and LS mice. The present findings of a lack of a strong association between sleep time and a brain polypeptide variant do not preclude the existence of a major gene effect contributing to variation in acute sensitivity to ethanol but are consistent with reports that multiple loci are responsible for the difference in ethanol sensitivity between SS and LS mice.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4041782 TI - Characterization of angiotensin binding in the African green monkey. AB - The observation that there are differences in the characteristics and distribution of angiotensin receptors in the central nervous system of mammalian species led to the analysis of angiotensin binding in a primate model, the African Green monkey. Initial studies using [125I]angiotensin II ([125I]AII) as the radioligand showed binding in peripheral tissues but little binding in the central nervous system. Conversely, binding studies using [125I]AIII as the radioligand indicated more central nervous binding with diminished peripheral binding. Specific binding of [125I]AIII is evident throughout the brain with high binding in the circumventricular organs, striatum, caudate nucleus, olfactory bulb and localized areas of the thalamus and cerebral cortex. This binding was found to possess many of the properties commonly associated with binding to membrane-bound receptors. The specifically bound radioligand extracted from incubations of [125I]AIII and central nervous tissue appears to be a product of the metabolism of [125I]AIII rather than the peptide itself. Binding of [125I]AII does occur in peripheral tissues and to a limited extent in the cerebellum, but to a different receptor from that characterized using [125I]AIII. These results are similar to those seen in the gerbil and raise questions concerning the utilization of the rat as the primary model for studying the biochemistry of the brain-angiotensin system in humans. PMID- 4041783 TI - Endoneurial oxygen tension and radial topography in nerve edema. AB - Endoneurial edema occurs in numerous human and experimental neuropathies. We tested the hypothesis that the resultant increase in intercapillary distance (ICD) may result in endoneurial hypoxia. Experimental galactose neuropathy (EGN) was chosen since in this model, edema is due to the accumulation of galactitol, which does not directly damage nerve fibers, so that it was possible to study the role of endoneurial edema alone. We measured endoneurial oxygen tensions (PnO2) using oxygen-sensitive microelectrodes and related PnO2 radial topography to ICD. We also determined local oxygen consumption (VLO2) and critical PnO2(PcritO2). EGN and age-matched controls were studied at 4 months. (1) Caudal nerve conduction velocity was reduced in EGN. (2) The PnO2 values were reduced in EGN and the PnO2 histogram was shifted into the hypoxic range. These changes were paralleled by a significant increase in ICD in EGN. (3) The radial topography of PnO2 in EGN differed from the relatively uniform distribution in control nerves. In EGN the subperineurial PnO2 was significantly lower than the PnO2 at the center of the fascicle. These changes were paralleled by a significantly greater increase in ICD in the periphery. (4) That the PnO2 reduction in EGN was significant is suggested by the marked reduction in VLO2 and the large percentage (greater than 75%) of intrafascicular regions that fell below PcritO2 in EGN. PMID- 4041784 TI - Amphetamine's effects on terminal excitability of noradrenergic locus coeruleus neurons are impulse-dependent at low but not high doses. AB - The actions of amphetamine in the locus coeruleus and its terminal fields in the frontal cortex were studied using extracellular recording to measure terminal excitability, firing rate and the probability of antidromic action potential invasion of the somatodendritic region in urethane anesthetized rats. At low dose (0.25 mg/kg), amphetamine increased terminal excitability. In comparison, subsequent administration of the highest dose (5.0 mg/kg, i.v.) of amphetamine tested suppressed neuronal firing and blocked antidromic action potential invasion of the somatodendritic region. Despite the absence of impulse traffic, high dose amphetamine reversed the effect of low dose amphetamine in the terminal field and decreased terminal excitability. The alpha 2 antagonist, yohimbine (0.5 mg/kg, i.v.), reversed the effects of high dose amphetamine on terminal excitability and somatodendritic invasion without reinstating neuronal firing. Noradrenergic autoreceptor agonists are known to decrease terminal excitability, whereas antagonists are known to increase terminal excitability. Thus, since low dose amphetamine produces the same effect on terminal excitability that antagonists do, it appears that low dose amphetamine may reduce autoreceptor activation by reducing norepinephrine release in frontal cortex as a consequence of inhibiting locus coeruleus neuronal firing. In contrast, high dose amphetamine acts like autoreceptor agonists do and decreased terminal excitability. Hence high dose amphetamine may increase norepinephrine release, even in the absence of impulse traffic. PMID- 4041785 TI - Brain palmitate incorporation in awake and anesthetized rats. AB - Uniformly labeled [14C]palmitate was injected intravenously in awake and barbiturate-anesthetized rats, and arterial plasma radioactivity due to unesterified [14C]palmitate was determined on plasma samples removed at timed intervals up to the time of death. Overall brain radioactivity was determined by liquid scintillation spectroscopy, and regional brain radioactivity was determined by quantitative autoradiography. The transfer constant, k, for the unidirectional uptake of radiotracer palmitate into the brain at 4 h was calculated from the brain radioactivity and the integrated plasma radioactivity from injection to 4 h. The unidirectional palmitate uptake was calculated as the product of k and the plasma concentration of unesterified palmitate. Barbiturate anesthesia reduced regional palmitate transfer constants and unidirectional palmitate uptakes into different brain regions by 40-60%. Palmitate incorporation into the brains of awake rats at 4 h represents uptake into structural brain components which contain lipids. The results indicate that pentobarbital anesthesia reduces this rate of incorporation by about half. PMID- 4041786 TI - Biochemical and immunohistochemical evidence for the presence of motilin in pig cerebellum. AB - The presence of motilin in rat and porcine cerebellum was investigated by using high performance liquid chromatography (HPLC) coupled with radioimmunoassay or immunohistochemistry. The antibodies used for this study were raised against synthetic gastrointestinal porcine motilin, which is, so far, the only known sequence of this peptide. The results obtained show the presence of a sharp peak of motilin-like immunoreactivity after HPLC of porcine cerebellum extracts, with an elution time corresponding to that of synthetic porcine motilin. Motilin-like immunoreactivity was also detected immunohistochemically in porcine cerebellum. However no motilin-like immunoreactivity was detected in rat cerebellum biochemically or immunohistochemically. This finding suggests that if a motilin like neuropeptide is present in rat cerebellum, its molecular form differs from that present in porcine cerebellum. PMID- 4041787 TI - Inhibition of the lordosis reflex in rats by intrahypothalamic infusion of neural excitatory agents: evidence that the hypothalamus contains separate inhibitory and facilitatory elements. AB - In attempts to activate lordosis-facilitating neural mechanisms in the ventromedial hypothalamus (VMH), neural excitatory agents were infused into the medial hypothalamus, and the effects of the infusions on the lordosis reflex and on the electrical activity of VMH neurons were studied. Surprisingly, bilateral intrahypothalamic infusion of glutamate (10 mM, 1.0 microliter/side) into behaving, ovariectomized, estrogen-treated rats displaying moderate lordotic responsiveness did not facilitate lordosis, but instead, resulted in a rapid (within a few minutes) and transient (recovery in about 20 min) inhibition of lordosis. Further experiments showed that this lordosis-inhibiting effect of glutamate was dose-related, and was completely blocked by prior infusion of a local anesthetic, procaine. Infusion of KC1 (1.5 or 15%, 1.0 microliter/side) also induced a dose-related, rapid and transient inhibition of lordosis, that was essentially identical to that induced by glutamate. Kainic acid (0.25 micrograms/0.5 microliter/side) also caused a rapid inhibition of lordosis, but the effect was long-lasting (days). The inhibition of lordosis by these agents was dissociated in time course, presence, and/or severity from effects on non lordotic behaviors. Electrophysiological studies showed that all three agents tested could excite multiunit activity of the VMH, and that the time courses of these excitations were closely comparable to those of the inhibition of lordosis induced by the respective agents. Altogether, these studies indicated that the excitation of certain medial hypothalamic neurons can inhibit the lordosis reflex. The implied lordosis-inhibiting neural mechanisms are separate from facilitatory mechanism(s), according to differences in latency, duration, and procaine-sensitivity of response. PMID- 4041788 TI - Binding of [3H]Ro 5-4864 in primary cultures of astrocytes. AB - Intact primary cultures of astrocytes display benzodiazepine receptors, which can be labeled with [3H]Ro 5-4864. Binding of [3H]Ro 5-4864 is specific, saturable and temperature dependent, being maximal at 0 degrees C. Scatchard analyses show a single population of high affinity binding sites with a Kd value of 6.7 nM and a Bmax value of congruent to 12,000 fmol/mg protein. The binding reaches equilibrium at congruent to 100 min, with k+1 of 0.0078 nM-1 X min-1 and is rapidly reversible with k-1 of 0.057 min-1. [3H]Ro 5-4864 binding is not modulated by GABA. Certain benzodiazepines (flunitrazepam, diazepam, Ro 7-3351) and dipyridamole displace this binding with IC50 values in the nanomolar range, whereas other benzodiazepines (alprazolam, clonazepam, chlordiazepoxide) as well as carbamazepine, phenytoin and phenobarbital have IC50 values in the micromolar range. These characteristics resemble those of Ro 5-4864 binding to brain membrane preparations reported by other authors and thus indicate that the cultured astrocytes are good models of their in vivo counterparts. PMID- 4041789 TI - Synchrony between cortical neurons during operant conditioning. AB - One hundred twenty five pairs of neurons were recorded simultaneously from precentral cortex of Macaca mulatta monkeys during an operant conditioning task. At the end of 5-min behavioral periods, a cross-correlation histogram was generated to look for relationships between the firing of the two cortical neurons. Eighty four (67%) unit pairs showed a significant coincidence of firing within 1 ms of each other. This relationship occurred regardless of whether the units' firing rate fluctuations were correlated or not. These data imply that in the majority of cases, the two units are probably more related than previously reported. PMID- 4041790 TI - Commissural and ipsilateral internuclear connection of vestibular nuclear complex of the cat. AB - Commissural and ipsilateral intrinsic connections of the vestibular nuclear complex of cats were investigated using retrograde transport of horseradish peroxidase (HRP). HRP was microiontophoretically injected into limited areas (0.2 0.5 mm in diameter) of the respective vestibular nuclei. In the commissural connections, major fibers were observed between the bilateral superior vestibular nuclei (SVN) and between the bilateral descending vestibular nuclei (DVN); a moderate number of fibers was found from the medial vestibular nucleus (MVN) to the contralateral MVN, SVN and lateral vestibular nucleus (LVN) and from the DVN to the contralateral LVN. Minor commissural connections were detected between the bilateral LVN. The ipsilateral internuclear connections of the vestibular nuclear complex were: (1) from the LVN, MVN and DVN to the SVN, (2) from the MVN and DVN to the LVN and (3) from the MVN to the DVN. Minor ipsilateral intrinsic connections were found from the SVN to the MVN. PMID- 4041791 TI - Monoamine release from dopamine-depleted rat caudate nucleus reinnervated by substantia nigra transplants: an in vivo electrochemical study. AB - Previous studies have shown that fetal substantia nigra (SN) transplanted into a cavity overlying a dopamine (DA)-denervated caudate nucleus can reverse a number of the behavioral abnormalities induced by the denervation. While some histochemical and physiological evidence suggests that this reversal is the result of a functional DA input from the transplant to the host brain, there is little direct evidence for transmitter release from ingrowing graft-derived nerve fibers. In the present work in vivo electrochemistry was used to analyse the magnitude, time course and spatial distribution of neurotransmitter releases evoked by local application of potassium (K+) from DA-depleted, SN transplant reinnervated striatum. Animals were injected unilaterally with 6-hydroxydopamine (6-OHDA) into the SN and screened by measuring apomorphine-induced rotation. Some were then given SN grafts, which were placed in a 'delayed cavity' just dorsal to the lesioned striatum. Nafion-coated graphite epoxy capillary (GEC) electrodes were employed for the electrochemistry to minimize signals derived from ascorbate or acidic DA metabolites. The GEC electrode was fixed to a K+-filled micropipette and this assembly was used to map the caudate nucleus of control, 6-OHDA-treated, and 6-OHDA-treated, grafted animals. The morphometric relationships between striatal recording sites and transplant location were subsequently verified histologically. Releases from striatal sites within 1.0 mm of the SN grafts were slightly, but not significantly, less than those obtained from control caudate.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4041792 TI - Morphologic and functional abnormalities that develop in kitten Purkinje neurons during maintenance for months after maturation in organotypic cultures. AB - The morphologic and functional properties of the Purkinje cells (P-cells) grown for 10-11 weeks in organotypic cultures from newborn kitten cerebella were studied and compared to cultures which had been grown for 4-5 weeks under the same standard conditions. Electrophysiological and morphological data were obtained from HRP iontophoretically labeled neurons and were quantified by means of computerized techniques. Extracellular recordings of spontaneous activity showed that the 10-11-week-old P-cells had a pacemaker-like firing rate whereas the P-cells aged 4-5 weeks in vitro displayed a bursting activity. The qualitative morphological data evidenced abnormal swellings both on dendritic and axonal processes of the 10-11-week-old P-cells which were not present on the 4-5 week-old P-cells. The quantitative data revealed a significant decrease in the overall size of the dendritic network of the 10-11-week-old P-cells mainly due to a reduction in the total dendritic length and in the total number of dendritic segments, whereas the individual segment lengths remained almost unchanged. Dendritic spine counts showed no decrease in the dendritic density of these older P-cells. Such data suggest that the changes observed in 10-11-week-old cultured P cells may be compared to the age-related changes occurring in vivo and that such in vitro models could be useful tools in the study of the pathology of aging. However, alternative factors other than senescence are discussed since they may account for some degenerative changes observed in the older cultured P-cells. PMID- 4041793 TI - Water deprivation increases anterior hypothalamic norepinephrine metabolism in the rat. AB - Rats were limited to 10 min of access to water per day. After 1 week, concentrations and rate of metabolism of dopamine, norepinephrine and epinephrine were determined in hypothalamic and limbic areas associated with regulation of water homeostasis. Chronic water deprivation caused hypovolemia, hypotension and ingestion of a large volume of water when water became available. Norepinephrine metabolism was consistently increased in samples containing the anterior hypothalamic nucleus, but no other catecholamine in any other brain area was significantly affected by the deprivation schedule. We conclude that the anterior hypothalamic nucleus is involved in the response to chronic disruption of water balance in the rat. PMID- 4041794 TI - The organization of neurons in the nucleus of the lateral lemniscus projecting to the superior and inferior colliculi in the rat. AB - The topographic organization of neurons in the dorsal nucleus of the lateral lemniscus (DNLL) which project to the superior and inferior colliculi was studied using the retrograde horseradish peroxidase (HRP) and the fluorescent double labeling methods. Neurons projecting to the superior colliculus (SC) are situated in the rostral portion of the DNLL, whereas those to the inferior colliculus (IC) are found in the caudal area of this nucleus. These two portions are completely separated from each other and no neurons projecting to both the SC and the IC are observed. In the dorsolateral part of the rostral portion of the DNLL, neurons projecting to the ipsilateral SC are found, whereas neurons projecting to the contralateral SC are located in the central to medial part of the nucleus, but no neurons sending collateral axons to both sides of the SC were observed. Neurons located in the central part of the caudal area of the DNLL project to the ipsilateral IC and neurons in the lateral and medial parts project contralaterally to the IC. Some of the neurons in the caudal part of the DNLL have divergent axonal branching projecting to both sides of the IC. In the ventral nucleus of the lateral lemniscus, labeled neurons were observed only when the HRP was injected into the ipsilateral IC. PMID- 4041795 TI - Longitudinal columnar organization within the dorsal motor nucleus represents separate branches of the abdominal vagus. AB - To identify the distribution of central preganglionics associated with each branch of the subdiaphragmatic vagus, the fluorescent tracer True Blue (TB) was administered intraperitoneally to rats with 4 out of 5 branches cauterized, and then, after 72 h, the animals were sacrificed for histological analysis. Each vagal branch contained the axons of a topographically distinct column of cells within the dorsal motor nucleus of the vagus (DMN). The columns representing the 4 branches with the largest numbers of efferents are organized as paired, bilaterally symmetrical, longitudinal distributions on either side of the medulla. Each DMN side contains a column occupying the medial two-thirds or more of the nucleus and corresponding to one of the gastric branches (left DMN, anterior gastric; right DMN, posterior gastric). Also on each side, the lateral pole of the DMN consists of a coherent cell column corresponding to one of the celiac branches (left DMN, accessory celiac; right DMN, celiac). The fifth branch, the hepatic, is represented by a limited number of somata forming a diffuse column largely coextensive with that representing the anterior gastric branch. At some levels of the DMN, the columns overlap. Labeled cells observed in the reticular formation were correlated in number, left-right ratios and response to vagotomy with those in the DMN, which suggests that they are displaced cells of the nucleus. Distributions of labeled cells in the nucleus ambiguus and the retrofacial nucleus were not tightly correlated with those of the DMN. An analysis of cell counts obtained for each of the individual branches suggests that vagal axons do not generally send collaterals through more than one branch. PMID- 4041796 TI - Widespread reductions in cerebral blood flow and metabolism elicited by electrical stimulation of the parabrachial nucleus in rat. AB - We have studied the effect of electrical stimulation of the parabrachial nucleus (PBN) and adjacent areas of dorsal pons on regional cerebral blood flow (rCBF) and glucose utilization (rCGU) in anesthetized (chloralose), paralyzed (tubocurarine) rats. rCBF and rCGU were measured in dissected tissue samples of 9 brain regions by the [14C]iodoantipyrine and [14C]2-deoxyglucose method, respectively. Electrical stimulation restricted to the medial parabrachial nucleus (PBNm, n = 5) elicited significant (P less than 0.05) reductions in rCBF in 7 out of 9 brain regions. Reductions were greatest in cerebral cortex (up to 35% in occipital cortex) and least in the white matter of the corpus callosum (23%). The effect on rCBF persisted after transection of the cervical sympathetic trunk (n = 5). In contrast, stimulation of the lateral portion of PBN (n = 5), periventricular gray (n = 5) and interestingly, the nucleus locus coeruleus (n = 5) failed to elicit similar changes in rCBF. PBNm stimulation also elicited decreases in rCGU (n = 4) in 5 out of 9 brain areas, most notably regions of cerebral cortex. The decreases in rCGU (delta rCGU) were linearly related to the decreases in rCBF (delta rCBF) according to the equation delta rCBF = 2.37 delta rCGU + 2.1 (r = 0.72; P less than 0.001). We conclude that excitation of neural pathways originating in, or passing through, PBNm elicits a widespread reduction in cerebral metabolism and secondarily in blood flow (secondary vasoconstriction). Since projections of the PBNm do not involve the entire cortex, it seems likely that the effect is mediated via inhibition of diffuse cortical projections through a subcortical site. PMID- 4041797 TI - Time-course and regional distribution of the metabolic effects of bromocriptine in the rat brain. AB - Local cerebral glucose utilization (LCGU) and motor behavior were examined in awake Fischer-344 rats after administration of the dopaminergic agonist bromocriptine (BROMO). LCGU was measured using the [14C]2-deoxyglucose technique in 63 brain regions at 1,2,3 or 4 h after BROMO 20 mg/kg, and at 4 h after BROMO 100 mg/kg i.p. At 2 h, LCGU was reduced significantly in 13% of the 63 regions examined. The affected regions are related to the topographical distribution of dopaminergic innervation in the brain. At 3-4 h, LCGU remained depressed in some of the above dopaminergic regions, but was elevated significantly in regions which are involved in sensorimotor function. BROMO also produced two behavioral effects depending on time after administration. Locomotor activity was depressed at 1-2 h, and stereotyped behavior appeared at 3-4 h. The time-dependent effects of BROMO may reflect progressively increasing brain concentrations of the drug or of its active metabolites. The coincidence of locomotor depression and reduction of LCGU in dopaminergic regions suggests a role of dopamine autoreceptors in regulation of motor function. Metabolic stimulation of many non-dopaminergic regions when stereotypy is evident suggests that circuit(s) involving these areas may contribute to stereotypy. PMID- 4041798 TI - Locus coeruleus lesions in the rat enhance the antinociceptive potency of centrally administered clonidine but not morphine. AB - The nucleus locus coeruleus (LC) has been implicated in the descending inhibition of spinal nociceptive dorsal horn neurons, spinal nociceptive reflexes and in the antinociception produced by morphine. To further explore the involvement of the LC in antinociception, bilateral electrolytic lesions in the LC were made in adult male Sprague-Dawley rats. Lesions in the LC did not alter the antinociception produced by morphine (2.5 and 5 micrograms) administered in the periaqueductal gray in either the tail-flick (TF) or hot-plate (HP) tests when tested 7 and 14 days after the lesions. Baseline nociceptive thresholds in the TF and HP tests likewise were not affected at 7 or 14 days post-lesion. In contrast, the antinociceptive potency of clonidine administered intrathecally on day 13 post-lesion was enhanced significantly in the TF test; the antinociceptive ED50 of the LC lesion group was 0.52 micrograms whereas that of the sham lesion group was 2.29 micrograms. The antinociceptive potency of clonidine administered systemically (750 and 500 micrograms/kg, s.c.) was also enhanced in the LC lesion group in the TF but not the HP test. Norepinephrine (NE) in the lumbar spinal cord was correlated negatively and significantly with the extent of destruction of the LC. The lumbar spinal content of NE was reduced maximally at 12 days post lesion (to 56% of control). The binding of [3H]clonidine in the lumbar spinal cord was slightly greater in the LC lesion than sham lesion group; the Bmax values were 42.4 fmol/mg protein and 35.5 fmol/mg protein for the LC lesion and sham lesion groups, respectively. It is suggested that the LC participates in the descending inhibition of spinal nociceptive transmission and that this inhibition may be mediated in the spinal cord by alpha-2 adrenoceptors located postsynaptically with respect to the NE terminals of the spinopetal LC efferents. PMID- 4041799 TI - Spontaneous electrical activity induced by herpes virus infection in rat sensory neuron cultures. AB - Dissociated cultures of rat dorsal root ganglion neurons were infected with a syncytial strain of herpes simplex virus type 1. Over 90% of neurons in infected cultures were spontaneously active and fired action potentials which, on membrane potential hyperpolarization, were replaced by depolarizing events similar to excitatory postsynaptic potentials. Amplitude analysis of these events produced populations described by the sum of several unitary events with Gaussian rather than binomial or Poisson distributions. Such spontaneous activity was blocked by tetrodotoxin but not by low calcium high magnesium solutions containing cadmium. Simultaneous recording from pairs of spontaneously active neurons revealed excitatory connexions between cells. It is suggested that virus-induced fusion of nerve cell processes induces electrical coupling between sensory neurons, and that the resulting electrical network supports spontaneous activity. PMID- 4041800 TI - Discharges of neurons in the midpontine dorsal tegmentum of mesencephalic cat during locomotion. AB - Discharges of neurons in the midpontine dorsal tegmental field (DTF neurons) were recorded and analyzed during locomotion and were compared with those of reticulospinal neurons (RS neurons) located lateral to the DTF area. The conduction velocity of the descending axon of the DTF neurons was significantly smaller than that of the RS neurons. During locomotion, the DTF neurons showed a tonic increase in the discharge rate. In contrast, the discharge rate of the RS neurons showed cyclic modulation in step with locomotion. PMID- 4041801 TI - Demonstration of the synaptic origin of primary afferent depolarisation (PAD) in the isolated spinal cord of the hamster. AB - Intracellular recordings have been made from 31 primary afferent fibres within the dorsal horn of an isolated mammalian spinal cord. In 17 fibres stimulation of an adjacent dorsal root evoked primary afferent depolarization (PAD); these fibres also showed spontaneous depolarizations. Replacement of the calcium in the perfusing medium by manganese blocked both evoked and spontaneous activity showing them to be of synaptic origin. Observations on the effects of current injection and of bicuculline support an involvement of GABA in the generation of PAD. PMID- 4041802 TI - Strychnine and L-allylglycine but not bicuculline and picrotoxin induce transsynaptic degeneration following transection of the inferior alveolar nerve in adult rats. AB - The effects of the convulsants strychnine, bicuculline, picrotoxin and L allylglycine on the transsynaptic destruction of medullary dorsal horn neurons were examined following transection of the inferior alveolar nerve in adult rats. Strychnine and L-allylglycine enhanced the transsynaptic effect of nerve transection and caused degeneration of many dorsal horn neurons, while bicuculline and picrotoxin did not. The removal of glycinergic and GABAergic postsynaptic inhibition appears to enhance the transsynaptic destructive activity which follows the peripheral nerve transection. PMID- 4041803 TI - Further indications for enhancement of retrograde transneuronal transport of WGA HRP by synaptic activity. AB - Factors affecting the retrograde transneuronal transport of wheat germ agglutinin conjugated with horseradish peroxidase (WGA-HRP), from spinal motoneurones to interneurones, have been studied in the cat. To this end, the location of transneuronally labelled interneurones was compared in animals which were awake or remained anaesthetized after WGA-HRP had been injected into the semitendinosus or the medial gastrocnemius nerve. In the anaesthetized animals motor axons of the injected nerves were stimulated selectively, to activate only Renshaw cells, or together with group I afferents, to activate also laminae V-VI interneurones with input from these muscles. The interneurones labelled in this study were distributed in different spinal cord regions than the interneurones labelled in preparations in which group I afferents of antagonist muscles were stimulated, as described in a previous study. The reported observations extend evidence of Harrison et al. that the retrograde transneuronal transport of WGA-HRP is facilitated by synaptic activity. PMID- 4041804 TI - Role of the paraventricular and ventromedial hypothalamic nuclear areas in the regulation of the pituitary-adrenocortical system. AB - The role of the paraventricular (PVN) and ventromedial (VMN) hypothalamic nuclei in the activation and inhibition of the pituitary-adrenocortical system was studied in chronic experiments on rabbits. The functioning of the pituitary adrenocortical system was estimated by changes in blood corticosteroid levels. PVN and VMN lesions resulted in a reduction of the stress-induced corticosteroid rise. VMN lesions resulted in smaller changes of the stress-induced response than PVN lesions while combined VMN and PVN lesions did not cause a larger reduction of the stress-induced activation than lesions of either area. The data obtained confirm that the PVN and VMN are connected in series. Hydrocortisone (100 micrograms/kg) administered intravenously 5 min before immobilization inhibits the stress-induced corticosteroid rise in intact rabbits. PVN and VMN lesions result in a reduction of the hydrocortisone inhibitory effect, PVN lesions having a greater effect than VMN ones. The PVN is of greater importance in both the activation and the inhibition of the pituitary-adrenocortical system than the VMN. PMID- 4041805 TI - Sodium-independent binding of [3H]cocaine in mouse striatum is serotonin related. AB - There was a highly significant correlation between IC50 values of various drugs in inhibiting the Na+-independent [3H]cocaine binding in the mouse striatum and their values in inhibiting the synaptosomal uptake of [3H]serotonin. In contrast, there was no correlation between the inhibition of binding in the absence of Na+ and the inhibition of [3H]dopamine uptake. Lesioning of serotonergic nerve terminals with 5,7-dihydroxytryptamine reduced the Na+-independent [3H]cocaine binding, without affecting the Na+-dependent binding. These results indicate that the bulk of the Na+-independent [3H]cocaine binding in the mouse striatum is associated with serotonergic nerve terminals. PMID- 4041806 TI - Electrophysiological analysis of potential arginine vasopressin projections to the ventral septal area of the rat. AB - Extracellular electrophysiological studies of neurons in the ventral septal region of the rat have examined afferent input from the paraventricular nucleus, bed nucleus of the stria terminalis and suprachiasmatic nucleus. Short latency excitatory or inhibitory orthodromic potentials were obtained following electrical stimulation of each nucleus, thereby providing evidence for these areas as a possible source of arginine vasopressin (AVP) fibers to the ventral septal region. These projections may mediate the reported antipyretic action of arginine vasopressin in the ventral septal region. PMID- 4041807 TI - Time-course of ultrastructural changes in regenerated optic fiber terminals of goldfish. AB - The ultrastructure of regenerated optic fiber terminals differs from normal terminals during the first 12 months following optic nerve crush. The area of the regenerated terminals occupied by axoplasm initially increases (1 month postcrush, mpc), then declines to a below normal level (8-12 mpc) and eventually returns to the normal level (16 mpc). The density of vesicles within the regenerated terminals remains initially the same (1 mpc), then increases (4-12 mpc) and finally returns to normal values by 16 mpc. The multiplicity of reestablished retino-tectal synapses gradually increased from an initially lower value at 1 mpc to the normal value by 4 mpc whereas the length of their synaptic contacts decreased from an initial elongation (1 mpc) to the normal length (4 mpc). PMID- 4041808 TI - Aluminum intoxication: a disorder of neurofilament transport in motor neurons. AB - In the rabbit, intrathecal administration of aluminum salts (AlCl3) induces accumulation of neurofilaments in nerve cells of the central nervous system. In motor neurons, the spatial pattern of neurofilamentous accumulation following aluminum intoxication suggests a defect in the axonal transport of neurofilament proteins. To test this hypothesis, we examined the distribution of radioactive cytoskeletal proteins in sciatic nerves of intoxicated and control animals. In the nerves of aluminum-injected animals, there was a 40% reduction in the relative amount of radioactive neurofilament proteins compared to tubulin. These results suggest that an abnormality in neurofilament transport may be important in the pathogenesis of the neurofibrillary pathology induced by aluminum intoxication. PMID- 4041809 TI - A calculation method for evaluating the time course of GABA removal from a synaptic cleft by presynaptic uptake systems. AB - A calculation method for evaluating the time course of gamma-aminobutyric acid (GABA) removal from a synaptic cleft by presynaptic uptake is suggested. The evaluation of the actual time required to remove GABA requires the knowledge of: (a) KM's and Vmax's (mol/min/mg protein) of the synaptosomal uptake systems in a certain brain area; (b) the synaptosomal volume per mg of protein in the synaptosomal preparation used; (c) the mean sphere diameter for synaptic boutons in the brain area considered and the proportion of GABAergic nerve terminals. PMID- 4041810 TI - Distribution and response characteristics of masseteric nerve-driven neurons in two separate cortical projection areas of cats. AB - Cortical projection areas and distribution and response characteristics of masseteric nerve-driven neurons (MDN) were studied by recording surface-evoked potentials and single neuronal activities elicited by stimulation of the contralateral masseteric nerve in cats. Neuronal activities of MDNs could be recorded in two separate cortical areas. One was located in laminae II-III of area 3b of the posterior part of the coronal gyrus (P), and the other in laminae IV-V of areas 3a and 6a beta of the anterior parts of the coronal and lateral sigmoid gyri (A). The majority of MDNs were driven by low-threshold muscle afferents (Group I and II). Peak latencies of MDNs in P were shorter than those in A. Intracortical microstimulation (less than 30 microA) in A produced oro facial movements while stimulation in P did not produce any motor effects. PMID- 4041811 TI - Iron concentration reduced in ventral pallidum, globus pallidus, and substantia nigra by GABA-transaminase inhibitor, gamma-vinyl GABA. AB - Recent histochemical studies indicate that there is considerable overlap of brain areas accumulating iron in oligodendrocytes with those in which GABA neurons terminate. The ventral pallidum, globus pallidus, substantia nigra and cerebellar nuclei are iron-rich areas, receive GABA-containing efferents, and have high concentrations of gamma-aminobutyric acid (GABA) and glutamic acid decarboxylase (GAD). The present study examines the effect of disruption of the metabolism of GABA on the accumulation of iron in GABAergic projection sites. Gamma-vinyl GABA, an enzyme activated inhibitor of GABA-transaminase, was injected unilaterally into the globus pallidus and adjacent striatum or into the substantia nigra of the rat brain. Additional animals received unilateral injections of saline into the same areas or an electrocoagulation lesion of the globus pallidus and surrounding striatum. Two days after injection or lesion all animals were perfused and 40 micron sections of the brain were processed with the Perls' + diaminobenzidine (DAB) histochemical method for iron. The intensity of iron stain was measured with densitometry. Gamma-vinyl GABA injection into the striatum/pallidum resulted in a significant reduction in iron concentration in the ipsilateral ventral pallidum, globus pallidus and substantia nigra. Gamma vinyl GABA injected into the substantia nigra reduced iron in the injection site. This study provides evidence that the presence of iron in the brain is related to the utilization of GABA. PMID- 4041812 TI - Distribution and chromatographic characterization of neuromedin B-like immunoreactivity in the human spinal cord. AB - The quantitative regional distribution of neuromedin B-like immunoreactivity in normal postmortem human spinal cord was studied by a specific radioimmunoassay. Neuromedin B-like immunoreactivity was found in highest concentration in the dorsal part of the sacral cord. Chromatographic analyses by gel permeation and reverse-phase high-pressure liquid chromatography revealed two major peaks of neuromedin B-like immunoreactivity and the prevalent molecular form, approx. 90% of the total immunoreactivity, was chromatographically identical to synthetic porcine neuromedin B. PMID- 4041813 TI - CNS effects of circulating CCK8: involvement of brainstem neurones responding to gastric distension. AB - Cholecystokinin octapeptide (CCK8) given i.v. or i.p. produces a variety of behavioural and CNS effects; these actions are probably exerted at a peripheral site but the neuronal pathways involved are uncertain. We show here that i.v. CCK8 acts on neurones in the n. tractus solitarius with an input from the stomach; cells are either excited or depressed by CCK8 and gastric distension, and responses to the two stimuli are always in the same direction. The responses to close arterial injection of CCK8 indicate a site of action within the splanchnic bed, and most probably a direct action on the vagal afferents mediating gastric mechanoreceptor discharge. PMID- 4041814 TI - Amygdala norepinephrine involved in two separate long-term memory retrieval processes. AB - Noradrenergic manipulation of the rodent amygdala results in time-dependent disruption of long-term memory for a one-trial aversive experience. Findings using both state-dependent and consolidation experimental procedures suggest that the norepinephrine system of the amygdala underlies not only consolidation-like mechanisms. There appear to be specific noradrenergic substrates for two or more memory retrieval processes which may be physiologically similar to either acquisition or later memory development involving aversive information. PMID- 4041815 TI - The separation and identification of enolase isozymes of brain and sciatic nerve by high-pressure liquid anion-exchange chromatography. AB - A rapid technique for separating and quantitating the three enolase isozymes present in rodent brain and sciatic nerve was developed using high-pressure liquid anion-exchange chromatography. At pH 7.9, one cationic and two anionic enzyme forms were separated with baseline resolution in an imidazole buffer containing ethylenediaminetetraacetic acid (EDTA) and magnesium. The recovery of enolase activity was 90% or greater for brain and 85% for sciatic nerve. Chromatography of liver and axon-free (degenerated) sciatic nerve allowed the identification of non-neuronal, hybrid, and neuron-specific enolase isozymes. These enzyme forms, respectively, constituted 40%, 29% and 19% of total activity in brain, and 63%, 13% and 4% of total activity in normal sciatic nerve. PMID- 4041816 TI - The suprachiasmatic nucleus of the human brain in relation to sex, age and senile dementia. AB - The suprachiasmatic nucleus (SCN) is considered to be the endogenous clock of the brain, essential for the ovulation cycle and the temporal organization of sleep wake patterns, among other things. Immunocytochemical staining with anti vasopressin as a marker permitted a morphometric study of this nucleus in the human brain, which revealed that the shape of the SCN is sexually dimorphic. The shape of the SCN was elongated in women and more spherical in men. In both sexes a decrease in SCN volume and cell number was observed in senescence (80-100 years). The latter change was especially pronounced in patients with senile dementia of the Alzheimer type (SDAT). This suggests the presence of a structural defect in the SCN which underlies the general disturbance of biological rhythms in senescence and SDAT. PMID- 4041817 TI - The vasopressin and oxytocin neurons in the human supraoptic and paraventricular nucleus; changes with aging and in senile dementia. AB - The neuropeptides vasopressin (AVP) and oxytocin (OXT) are supposed to be involved not only in peripheral functions (e.g. diuresis, labour and lactation) but also in central processes that are frequently disturbed during aging and senile dementia (e.g. fluid and electrolyte homeostasis and cognitive functions). A concomitant decrease in activity of the hypothalamo-neurohypophyseal system (HNS) with aging has been postulated in the literature, but has not yet been established. In order to investigate possible age-related changes in the human HNS, immunocytochemically identified AVP and OXT neurons in the paraventricular and supraoptic nucleus (PVN and SON) were analysed morphometrically in subjects from 10 to 93 years of age, including patients with senile dementia of the Alzheimer type (SDAT). Cell size was used as a parameter for peptide production. Mean profile area of OXT cells did not show any significant changes with increasing age. Mean profile area of AVP cells, however, showed an initial decrease up to the sixth decade of life, after which a gradual increase was observed. Size of AVP and OXT cell nuclei did not change significantly with aging. Observations in brains from patients with SDAT were within the range for their age group. The present results do not support degeneration or diminished function of the HNS in senescence or SDAT, as generally presumed in the literature, but suggest an activation of AVP cells after 80 years of age. The activation of AVP cells in senescence is in accordance with previous findings in the aged Wistar rat. PMID- 4041818 TI - Modification of neuronal discharge along the ascending tectofugal pathway during visual conditioning. AB - Visually conditioned heart-rate change in the pigeon has been developed as vertebrate model system for analysis of associative learning. The visual pathways transmitting the conditioned stimulus information were identified, and neurophysiological analyses during conditioning were then undertaken to determine if these pathways behave merely as input lines or undergo training-induced modification. After finding that the retinal output is invariant with training, we investigated the central visual pathways, beginning with the tectofugal pathway. During conditioning single neurons in the nucleus rotundus and ectostriatum, the thalamic and telencephalic relays of the tectofugal pathway, showed enhancement of their phasic light-evoked responses. In contrast, the initial phasic responses attenuated during non-associative training. The rate at which these discharge modifications developed paralleled the development of the behavioral response. Thus, the tectofugal pathway shows plasticity during conditioning and does not behave merely as an input channel for the conditioned stimulus. PMID- 4041819 TI - Coping and seizure susceptibility: control over shock protects against bicuculline-induced seizures. AB - Rats were either given 80 escapable shocks, yoked inescapable shocks, restraint or given no treatment. Two hours later all subjects received i.p. injection of bicuculline (4, 6 or 8 mg/kg) and were immediately tested for latency to initial myoclonic jerk and clonus. The latency to clonic convulsion was dramatically affected by prior shock treatment, and the direction of this change depended upon the escapability/inescapability of the shock. Subjects that were given escapable shock showed a delay of onset to seizure, while subjects inescapably shocked demonstrated a decreased latency to clonus in comparison to restrained and naive controls. It was also demonstrated that if the subjects were tested immediately following a stress experience, both the 80 escapable and inescapable shock condition protected against bicuculline-induced seizures in comparison to the control condition. Finally Experiment 2 confirmed a previous finding that less stress, i.e., 20 inescapable shocks, protects against seizures when the animals are challenged with bicuculline either immediately or 2 h later. Our suggestion is that control over stress may facilitate GABAergic transmission, and this may be the mechanism whereby coping protects against the behavioral and physiological disruption produced by exposure to a stressor. PMID- 4041820 TI - Selectivity between faces in the responses of a population of neurons in the cortex in the superior temporal sulcus of the monkey. AB - There is a population of neurons in the cortex in the middle and anterior part of the superior temporal sulcus (STS) of the monkey with responses which are selective for faces. If, consistent with the effects of damage to the temporal lobe, these neurons are involved in face recognition or in making appropriate social responses to different individuals, then it might be expected that at least some of these neurons might respond differently to different faces. To investigate whether at least some of these neurons do respond differently to different faces, their responses were measured to a standard set of faces, presented in random sequence using a video framestore. It was found that a considerable proportion of the neurons with face-selective responses tested (34/44 or 77%) responded differently to different faces, as shown by analyses of variance. An index of the discriminability of the most and least effective face stimulus (d') ranged between 0.2 and 5.0 for the different neurons. Although these neurons often responded differently to different faces, they did not usually respond to only one of the faces in the set, so that information that a particular face had been shown was present across an ensemble of neurons, rather than in the responses of an individual neuron. These findings indicate that the responses of these neurons would be useful in providing information on which different behavioral responses made to different faces could be based. These neurons could thus be filters, the output of which could be used for recognition of different individuals and in emotional responses made to different individuals. PMID- 4041821 TI - Ventral cochlear nucleus neural discharge characteristics in the absence of outer hair cells. AB - The role of the cochlear outer hair cell (OHC) in auditory processing remains poorly understood. The OHCs possess an independent afferent innervation which constitutes 5-10% of cochlear afferent neurons and which appears to project to the cochlear nucleus (CN). Whether the OHCs contribute to the processing of auditory signals in the CN has not been determined. To address this question, kanamycin ototoxicity was used to produce selective OHC loss while leaving the inner hair cell (IHC) population largely intact, in the basal portion of the cochlea of chinchillas. Single unit responses were then recorded in the ventral cochlear nucleus (VCN), and compared to responses in untreated subjects. Many of the changes observed in VCN neural responses reflected changes which have previously been reported in the VIIIth nerve. However, frequency tuning curve tip segments which were normal in both bandwidth and length were observed in approximately 22% of the units associated with regions of complete OHC loss and preservation of IHCs. This has not been reported in previous OHC lesion studies. Also, first spike latency was found to be significantly lengthened for units associated with the OHC free regions. Those features of VCN neural responses which first arise within the CN, such as non-primary-like post-stimulus-time histogram response patterns, were unaffected by OHC loss. These results suggest that afferent fibers associated with OHCs do not play a major role in signal processing in the VCN. PMID- 4041822 TI - Some factors that influence the decrement in the response to GABA during its continuous iontophoretic application to hippocampal neurons. AB - The response decrement that occurs during continuous iontophoretic application of GABA to hippocampal neurons was characterized by intracellular methods in the rat hippocampal slice. Using several paradigms that compared the responses to GABA with those to poorly transported analogues, we then identified a large component of this decrement that appeared to be independent of GABA uptake and metabolism, and that is probably independent of intracellular chloride accumulation as well. This decrement, which both developed and recovered with half times that average between 3 and 5s, is too brief to directly account for long-term plasticity of the GABA synapse. However, its time course is appropriate to participation in the development of cellular responses to brief flurries of GABA-mediated inhibitory postsynaptic potentials that may occur normally, or that may occur abnormally during a seizure or artificial tetany. PMID- 4041823 TI - The development of the Bergmann fiber palisades in the cerebellum of the normal rat and in the weaver mouse. AB - The development of the Bergmann fiber palisades in the rat cerebellum was investigated by PAP immunocytochemistry using an anti-GFAP antibody. The Bergmann fibers are organized in parallel palisades as early as the second postnatal day and probably even earlier. This observation suggests that the organization and orientation of the palisades precedes the orientation of the parallel fibers in the same direction. Some Bergmann fiber palisades were also found in the adult homozygous weaver mouse, although it was more difficult to find palisades in these mutants than in the heterozygous or normal animals. The results are consistent with the hypothesis that during the early stages of cerebellar development the Bergmann fiber palisades organize the orientation of the parallel fibers in the longitudinal plane of the folium. PMID- 4041824 TI - Metabolic labeling associated with index finger stimulation in monkey SI: between animal variability. AB - Four monkeys (Macaca fascicularis) were stimulated with an identical intermittent vertical displacement (flutter) stimulus on the tip of the index finger and received intravenous [14C]2-deoxyglucose (2-DG). The majority of metabolic labeling was found to exist in areas 3b and 1 of the anterior parietal cortex (SI) in the form of intermittent patches, which extended vertically across the cortical laminae. When the patches were traced through adjacent sections and reconstructed to produce a 2-dimensional map, it became evident that the patches of label combined to form a complex spatial pattern consisting of strips. Although the flutter stimulus was applied to a spatially restricted peripheral field, the metabolic pattern was always complex and widely distributed within SI. Nevertheless, the 2-DG patterns produced in the different animals stimulated with the same stimulus were strikingly similar. The relationships between descriptions of the SI index finger representation based on neurophysiological mapping data and the distribution of 2-DG uptake are described. The reproducibility of the 2 DG labeling pattern and relationship to neurophysiological maps suggests that the 2-DG mapping method provides a potent and useful tool for the investigation of stimulus representation in the somatosensory cortex. PMID- 4041825 TI - Rat C6 glioma cells contain type I as well as type II corticosteroid receptors. AB - Rat brain cytosol contains Type I corticosteroid receptors. Unlike Type II (glucocorticoid) receptors, Type I receptors have high affinity for the endogenous corticosteroids - aldosterone, deoxycorticosterone, and corticosterone - and much lower affinities for synthetic glucocorticoids. In the present study, we report that Type I corticosteroid receptors are present in C6 glioma cells. Type I receptors were identified in C6 cell cytosol and whole cells by the binding of [3H]aldosterone. The specific glucocorticoid RU 26988 was used to block Type II receptors. Measured in whole C6 cells, Type I receptors had a density of 2.1 +/- 1.1 fmol/10(6) cells and a dissociation constant (Kd) for [3H]aldosterone of 0.41 +/- 0.06 nM. The density of Type I receptors was only 2% of the density of Type II corticosteroid receptors (96 +/- 7 fmol/10(6) cells), measured in whole C6 cells by [3H]triamcinolone binding. The steroid specificity of glial cytosolic Type I receptors (deoxycorticosterone greater than corticosterone greater than aldosterone greater than dexamethasone greater than triamcinolone much greater than RU 26988) was identical to the steroid specificity of Type I receptors in rat brain cytosol. The potency of deoxycorticosterone was somewhat reduced when measured in whole cells. The steroid specificity of the Type I receptor differed markedly from that of the Type II (glucocorticoid) receptor (triamcinolone greater than dexamethasone greater than RU 26988 corticosterone greater than deoxycorticosterone greater than aldosterone). Since Type I receptors in the kidney mediate effects of aldosterone upon renal transport of sodium and potassium, it is proposed that glial Type I corticosteroid receptors may be involved in the regulation of glial ion transport.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4041826 TI - The comparative distribution of [Lys8-Asn9]-neurotensin8-13-like immunoreactivity in chicken and rat tissues. AB - The presence of [Lys8-Asn9]-neurotensin8-13-like immunoreactivity was studied by radioimmunoassay in chicken and rat tissues. In the chicken, [Lys8-Asn9] neurotensin8-13-like immunoreactivity showed a wide distribution throughout the central nervous system and the gastrointestinal tract, and the immunoreactive material co-eluted with the synthetic peptide on reverse-phase high performance liquid chromatography. In the rat, [Lys8-Asn9]-neurotensin8-13-like immunoreactivity was widely distributed when 0.1 M HCl was used as the extraction procedure. However, the immunoreactive material did not co-elute with the synthetic peptide on reverse-phase high performance liquid chromatography; moreover, the addition of the aspartic proteinase inhibitor pepstatin to the extraction medium resulted in a large reduction in the levels of [Lys8-Asn9] neurotensin8-13-like immunoreactivity and no immunoreactive material could be detected when the tissues were extracted using acetone/HCl. The present results therefore indicate that [Lys8-Asn9]-neurotensin8-13-like immunoreactivity is not present in rat tissues. That which was detected resulted from an extraction artefact. PMID- 4041827 TI - Structure-activity studies with carboxy- and amino-terminal fragments of neurotensin on hypothalamic neurons in vitro. AB - The purpose of this study was to determine the structural requirements for the activity of neurotensin (NT1-13) on preoptic/anterior hypothalamic (POAH) neurons in vitro. Standard explant culture electrophysiological techniques were employed. NT was administered to POAH cultures through the superfusion fluid, or, to the vicinity of individual neurons by pressure ejection (0.5-10 psi) from micropipettes. Computer-generated, peri-event histograms were used to quantitate neuronal responses. Pressure ejection of NT1-13 (50 pM to 1 microM) consistently produced an excitatory effect on 30 of 42 neurons. The remaining cells were either inhibited or unaffected. Application of the C-terminal hexapeptide, NT8 13, but not the N-terminal octapeptide, NT1-8 (less than or equal to 1 mM), produced an excitatory response in 21 of 30 neurons, but was less potent than NT1 13. Application of an N-acetylated NT8-13 fragment (NTAC8-13) produced a response that was similar to that produced by NT8-13. The excitatory effects of NT1-13 and NT8-13 were maintained in medium which effectively blocked synaptic transmission (0 mM Ca2+/12 mM Mg2+ 1 mM EGTA). These data indicate that the C-terminal hexapeptide, but not the N-terminal octapeptide, produces a dose-related, excitatory effect on single neurons in the POAH in vitro. The persistence of these effects in Ca2+-free medium supports a postsynaptic site of action for these peptides. PMID- 4041828 TI - Extracellular pH changes in the superfused cat carotid body during hypoxia and hypercapnia. AB - Extracellular pH changes were measured in the superfused cat carotid body with double barreled pH glass microelectrodes, under constant pH (7.45 +/- 0.02), temperature (35 degrees C) and flow (3.6 ml/min) of the superfusion medium. Changes of pO2 in the medium from about 188 Torr (30% O2) to 35 or 12 Torr (5% and 2% respectively) called hypoxia, induced a change of the pH signal of about 0.1 units indicating acidification of the tissue. Medium pH monitored with a pH macroelectrode did not change during hypoxic stimulation. An increase of pCO2 in the medium from about 20 Torr (3% CO2, pH 7.45 +/- 0.02) to 70 Torr (12% CO2, pH 6.98 +/- 0.01) called hypercapnia, under constant pO2 (188 +/- 2 Torr), temperature (35 degrees C) and flow (3.6 ml/min) resulted in acidification of the tissue of about 0.3 pH units. Extracellular pH changes during hypoxia did not occur when the superfusion medium had no glucose; however, pH changes during hypercapnia persisted under these conditions. The hypoxic and hypercapnic chemosensory response of the sinus nerve were decreased or abolished during glucose deprivation in a time-dependent manner. Replacement of glucose with 2 deoxyglucose in the medium led to a similar pattern, i.e. inhibition of the hypoxic and hypercapnic chemosensory nerve response and of the extracellular hypoxic pH changes. These results indicate that glycolysis takes place and contributes to O2 and CO2-chemoreception in the carotid body. PMID- 4041829 TI - Hydrogen ion buffering during complete brain ischemia. AB - As a first step to quantify [H+] changes in brain during ischemia we used H+ selective microelectrodes and enzyme fluorometric techniques to describe the relationship between interstitial [H+] ([H+]o) and peak tissue lactate after cardiac arrest. We found a step function relationship between [H+]o and tissue lactate rather than the linear titration expected in a homogeneous protein solution. Within a blood glucose range from 3-7 mM, brain lactate rose from 8-13 mmol/kg along with a rise in [H+]o of 99 +/- 6 nM(0.44 +/- 0.02 pH). At higher blood glucose levels (17-80 mM), brain lactate accumulated to levels of 16-31 mmol/kg; concurrently [H+]o rose by 608 +/- 16 nM (1.07 +/- 0.02 pH). The unchanging level of [H+]o between 8-13 and 16-31 mmol/kg lactate implies that [H+]o is at a steady-state, but not equilibrium with respect to [H+] in other brain compartments. We propose that ion-transport characteristics of astroglia account for the observed relationship of [H+]o to tissue lactate during complete ischemia and suggest that brain infarction develops after plasma membranes in brain cells can no longer transport ions to regulate [H+]. PMID- 4041830 TI - Distribution of histaminergic, muscarinic and serotonergic binding sites in cat spinal cord with emphasis on the region surrounding the central canal. AB - [3H]Quinuclidinyl benzilate (QNB), [3H]lysergic acid diethylamide (LSD) and [3H]pyrilamine were used with radiohistochemistry to determine the distribution of muscarinic, serotonergic and histaminergic binding sites, respectively, in cat spinal cord. Each ligand displayed a unique pattern of binding sites in the superficial laminae of the dorsal horn [3H]Pyrilamine binding sites were localized most superficially, while [3H]LSD binding sites were densest in the region of the laminae II/III border. The distribution of [3H]QNB binding sites partially overlapped those of LSD and pyrilamine. In the region surrounding the central canal, pyrilamine binding sites were concentrated within a zone 100 microns lateral to the canal while [3H]QNB and [3H]LSD binding sites were localized outside of this zone. The distribution of binding sites in the region surrounding the central canal may provide an important neurochemical correlate for lamina X in the cat as defined by Rexed. PMID- 4041831 TI - Local cerebral glucose utilization in the free moving mouse: a comparison during two stages of the activity-rest cycle. AB - The 2-deoxy-D[1-14C]glucose ([14C]DG) technique has been applied to the free moving mouse for the quantitative determination of local cerebral glucose utilization (LCGU). Reproducible values for LCGU were obtained indicating that the [14C]DG method had a sufficient resolution power to allow visualization and quantification of very small structures provided that glucose and [14C]DG plasma concentrations were measured on microsamples, autoradiographs prepared from proper tissue sections and suitable techniques used for analysis of the maps thus obtained. LCGU was measured in free moving mice during two stages of the light dark cycle, one corresponding to a period of rest and the other to a period of high motor activity. In the two groups of animals LCGU was heterogeneous in the grey matter, the highest values being found in the auditory regions, the cerebellar and vestibular nuclei. LCGU was found to be lower in drowsy animals during the day than in active animals during the night and the difference was significant in the 8 following structures: the sensorimotor cortex, the septal nuclei, the nucleus of the olfactory tract, the basal amygdaloid nucleus, the ventral nucleus of the thalamus, the lateral geniculate body, the medial geniculate body and the auditory cortex. On the contrary, the suprachiasmatic nucleus was very active during the day and relatively inactive during the night as previously reported in the rat. PMID- 4041832 TI - An in vivo model to quantify motor and sensory peripheral nerve regeneration using bioresorbable nerve guide tubes. AB - An in vivo preparation is presented to study the rate and time course of motor and sensory axonal regeneration. The cut ends of a transected sciatic nerve were inserted into each end of a 5-6 mm non-toxic and bioresorbable nerve guide tube to create a 4 mm nerve gap in adult mice. Subsequently, cell bodies in the ventral spinal cord and L3-L5 dorsal root ganglia that had regenerated axons across the gap were retrogradely labeled with horseradish peroxidase (HRP). The HRP was applied 3 mm distal to the nerve guide and was accessible only to axons that had regenerated through the nerve guide. Labeled cells were counted in 40 micron serial sections at 2, 4 and 6 weeks after initial nerve transection. The results indicate a significant increase in the number of labeled motor and sensory cell bodies over time. By 6 weeks after transection, approximately two thirds as many ventral horn motor cells and one third as many dorsal root ganglion sensory cells were labeled as in control non-transected animals. These data serve as a baseline to compare differential effects of additives to the nerve guide lumen in terms of sensory and motor neuron response. PMID- 4041833 TI - Brattleboro rats display increased sensitivity to arginine vasopressin-induced motor disturbances. AB - Motor disturbances observed in Brattleboro rats (homozygous for the diabetes insipidus (DI) trait) following a first intracerebroventricular injection of 1.0 microgram of arginine vasopressin (AVP) were not significantly different from those of the parent Long-Evans (LE) strain. These disturbances consisted of periods of staring and immobility, locomotor difficulties and discrete myoclonic jerks, often followed by scratching behavior. Following a second central injection of 10.0 ng AVP, however, the DI strain exhibited more pronounced motor disturbances than the LE strain. This increased sensitivity of the DI strain to the behavioral actions of AVP does not appear to be due to a generalized decrease of seizure threshold, since no significant differences were observed between the two strains in their susceptibility to convulse following pentylenetetrazol. As the behavioral and motor effects of AVP appear to be receptor-mediated, these findings suggest that homozygous DI rats possess central AVP receptors, which, in the absence of endogenous vasopressin, may have increased sensitivity to a second central injection of AVP. PMID- 4041834 TI - Seizures induced by intraventricular microinjection of ionized cobalt in the rat- a new experimental model of epilepsy. AB - A new animal model for epilepsy was successfully produced by microinjection of cobaltous chloride into the lateral cerebral ventricle of the rat. The median convulsive dose (CD50) and the median lethal dose (LD50) of CoCl2 was 0.45 microM/10 microliters (0.27-0.77 microM/10 microliters) and 1.07 microM/10 microliters (0.73-1.57 microM/10 microliters), respectively. The behavioral changes, electrocorticogram (ECoG), and the action of 5 classical anticonvulsants were studied using this new model. Seizures induced by cobaltous chloride are clinically similar to those produced by systemic administration of kainic acid and amygdala kindling. These are characterized by staring spells, wet dog shakes, mild convulsive movements, and stereotyped convulsions. ECoG findings demonstrated a unique epileptic burst during the wet dog shakes. Generalized epileptiform discharges were seen during typical seizures. The burst of spikes first occurred in the opposite temporal and frontal regions; and then became generalized. Among the 5 anticonvulsants studied, phenobarbital (30 mg/kg) and nitrazepam (3 mg/kg) completely antagonized the seizures; carbamazepine showed a moderate effect; and phenytoin as well as sodium valproate showed little effect. It is postulated that the seizures induced by cobaltous chloride may originate in the limbic system; and that cobalt ions are responsible for the seizure-inducing action. The mechanism remains to be investigated. PMID- 4041835 TI - Organization of diencephalic dopamine neurones projecting to the spinal cord in the rat. AB - Using the aluminium-formaldehyde method for visualization of catecholamines in combination with injections of the fluorescent retrograde tracer True Blue we have studied those diencephalic dopamine (DA)-containing cell groups which have been proposed to give rise to the DA innervation of the spinal cord and investigated the organization of the diencephalospinal DA system in detail. The A13 cell group was found to contain 370, and the A11 cell group 140, DA-producing cells on each side, whereas only very few such cells were found in the paraventricular hypothalamic nucleus. Tracer injections into the spinal cord labelled only DA cells within the A11 group. The overall majority of labelled cells were found ipsilaterally but some cells were also found contralaterally indicating the existence of a minor crossed dopaminergic projection to the spinal cord. Large tracer injections which covered the hemicord at different levels generally resulted in very similar distributions and numbers of retrogradely labelled DA cells. The labelled DA-containing cells constituted 30-50% of the total number of labelled neurones in the ipsilateral A11 area and about 20-40% of the total number of DA containing cells in this area were labelled. Small injections that did not extend into the nucleus reticularis or the adjacent part of the lateral funiculus failed to label any diencephalic DA cells but usually labelled some non-DA cells in the A11 area. It is concluded that the diencephalospinal DA neurones have long axons that extend over several segments and possibly traverse the entire length of the spinal cord, giving off collateral branches at various levels. From the anatomical data of the present study and previous pharmacological and electrophysiological findings it seems possible that diencephalospinal DA neurones could modulate both sympathetic activity and nociception. PMID- 4041836 TI - Reinstatement of binocular depth perception by amphetamine and visual experience after visual cortex ablation. AB - In adult cats with bilateral visual cortex ablation the complete deficit in binocular depth perception, as measured on a visual cliff, was reversed by 4 doses of amphetamine. The amphetamine-induced recovery endured after the amphetamine treatment was discontinued. This enduring recovery of function was not obtained if the animals were housed in the dark during drug intoxication. Therefore, both amphetamine intoxication and visual experience are simultaneously required for recovery of binocular depth perception after visual cortex ablation. PMID- 4041837 TI - Long-term depression of parallel fibre synapses following stimulation of climbing fibres. AB - The results from several investigations suggest that climbing fibres heterosynaptically depress parallel fibre responses in Purkinje cells. In the present investigation the mechanism behind the depression has been studied by extracellular recording of responses in single Purkinje cells, evoked by electrical stimulation of parallel fibres and climbing fibres. The results show that a short time of conjunctive stimulation of climbing fibres and parallel fibres results in a long-lasting depression of the parallel fibre responses and that this depression can be prevented if the Purkinje cells are inhibited during the conjunctive stimulation. Since inhibition has been shown to shorten or abolish the long-lasting plateau potentials which are evoked by climbing fibre impulses this finding supports the assumption that the climbing fibre evoked plateau potentials mediate the heterosynaptic depression of parallel fibre responses. PMID- 4041838 TI - Electrophysiological evidence that circulating angiotensin II sensitive neurons in the subfornical organ alter the activity of hypothalamic paraventricular neurohypophyseal neurons in the rat. AB - Thirteen neurons in the subfornical organ (SFO) were antidromically activated by electrical stimulation of the paraventricular nucleus (PVN) in the rat. The activity of these identified SFO neurons was excited by intravenous injection of angiotensin II (AII). Electrical stimulation of the SFO produced orthodromic excitation (40%) and inhibition (40%) of the activity of putative vasopressin (VP)-secreting PVN neurons. These results suggest that circulating AII sensitive SFO neurons with efferent projections to the PVN have both excitatory and inhibitory influences on the activity of putative VP-secreting neurons in the PVN. PMID- 4041839 TI - Effects on the caudate spindle in rats of taurine and gamma-aminobutyric acid (GABA) microinjected into the substantia nigra: involvement of the dopaminergic system. AB - Spindle bursts (caudate spindle) were recorded from the frontal cortex in rats. The bilateral intranigral microinjection of taurine suppressed the caudate spindle, whereas the same dose of gamma-aminobutyric acid (GABA) did not suppress the caudate spindle. These results indicate that suppression of the caudate spindle induced by taurine may relate to activation of the nigrostriatal dopaminergic neurons. PMID- 4041840 TI - L-ascorbic acid-induced DNA strand breaks and cross links in human neuroblastoma cells. AB - The effect of high concentrations of L-ascorbic acid on the in vivo and in vitro growth of human neuroblastoma has been investigated. Directly implemented into cell culture it decreased the DNA, RNA and protein synthesis, and mitosis of neuroblastoma cells, without affecting normal neuronal cells. In vivo treatment of young nude mice bearing human neuroblastoma with 500 mg/kg L-ascorbic acid for the first 10 days markedly inhibited the growth of tumor mass. As determined by alkaline elution, both DNA strand breaks and DNA cross links were observed in tumor cells treated with 1 X 10(-4) M L-ascorbic acid for 2 h. DNA-DNA and DNA protein cross links in cells treated with L-ascorbic acid were revealed by the proteinase potassium assay. The results indicated that L-ascorbic acid can be a very effective and selective agent against human neuroblastoma. PMID- 4041841 TI - Presence of unmyelinated axons in the spinal root of the feline accessory nerve. AB - The spinal root of the accessory nerve was studied electron microscopically at different levels in 3 adult cats. It was found that this nerve contains several unmyelinated axons. In the main nerve trunk the proportion of unmyelinated axon profiles was 27% at the level of the foramen magnum. In juxtamedullary root fascicles near the PNS/CNS transition the proportion of unmyelinated axons was lower and these axons tended to occupy superficial positions in the fascicles. No intrafascicular unmyelinated axons were found in the immediate vicinity of the PNS/CNS transition but bundles of unmyelinated axons occurred in the surrounding pia mater. The findings suggest that unmyelinated axons in the spinal accessory nerve contribute to the pial vasomotor and/or sensory innervation. PMID- 4041842 TI - Cerebral alteration in calmodulin levels associated with the induction of physical dependence upon ethanol in rats. AB - Calmodulin levels were measured in different areas of brain in rats rendered physically dependent and after single doses (6 g/kg) of ethanol. After single doses of ethanol no changes in the calmodulin levels were found in the cortex, but those in the hippocampus and caudate nuclei were increased while those in the cerebellum were reduced. In the dependent intoxicated (prodromal) rats, calmodulin levels were elevated in all these regions except the cerebellum. In rats undergoing ethanol withdrawal syndrome, the calmodulin levels decreased in all regions of the brain except caudate nuclei. PMID- 4041843 TI - Peripheral sensory nerve fibers that dichotomize to supply the brachium and the pericardium in the rat: a possible morphological explanation for referred cardiac pain? AB - Two fluorescent dyes, 'True Blue' and 'Diamidino Yellow' were injected, respectively, into the pericardial sac and into the medial brachial cutaneous nerve or subcutaneously into the medial side of the brachium. Double-labelling was observed in ipsilateral dorsal root ganglia neurons of spinal cord segments C8, T1 and T2, indicating that dichotomizing afferent fibers supply both the pericardium and the brachium. This finding provides a possible morphological explanation for referred cardiac pain. PMID- 4041844 TI - Dopamine changes the shape of action potentials in hippocampal pyramidal cells. AB - Dopamine was found to have two electrophysiological effects on CA1 pyramidal cells in rat hippocampal slices. It increased the slow afterhyperpolarisation caused by a slow Ca2+-activated K+ conductance and it had an effect on action potentials that is postulated to be due to an increase in a fast Ca2+-activated K+ conductance. A given CA1 cell showed either one or both of the two responses to dopamine, or no response. PMID- 4041845 TI - Somatosensory cortex in macaque monkeys: laminar differences in receptive field size in areas 3b and 1. AB - We have examined receptive field sizes of neurons in granular, supragranular and infragranular layers within somatosensory cortical areas 3b and 1 in macaque monkeys. Receptive fields of neurons in layer 4 are smaller than receptive fields of neurons above or below layer 4. In addition, neurons in area 1 have larger receptive fields than neurons in corresponding layers of area 3b. PMID- 4041846 TI - Baclofen attenuates hyperpolarizing not depolarizing responses of caudate neurons in cat. AB - The effects of baclofen, a gamma-aminobutyric acid (GABA) analogue, were studied on the intracellular responses of caudate neurons to cortical and thalamic stimulation. Systemic or intracaudate injections of baclofen did not reduce the initial excitatory postsynaptic potential (EPSP) to these stimuli; however, it did completely block evoked hyperpolarizations. These results suggest that the GABA-b receptor (one possible site of baclofen action) is not found on the corticostriate synaptic terminals. Furthermore, our results clearly indicate that evoked hyperpolarizations recorded in caudate neurons are not the result of cortical disfacilitation. PMID- 4041847 TI - Neural correlates of female song in tropical duetting birds. AB - Duetting involves production of song by female and male birds in close temporal coordination. We studied the neural network controlling song in 3 tropical duetting species. The volumes of song control regions (SCRs) in the brain, neuronal density in nucleus robustus of the archistriatum (RA) which is one of these SCRs, total number of neurons in RA, and somal size of neurons in RA were measured and compared to values published for zebra finches and canaries in which only males sing. The extent of sexual dimorphism in SCR volumes, RA neuronal density, and total neuronal number in RA varied in a graded fashion across species and was correlated with extent of sexual dimorphism in song repertoire size in any one species. Somal size of RA neurons was identical in males and females of each duetting species, regardless of relative repertoire size. Of all SCRs, the caudal nucleus of the ventral hyperstriatum appeared to have the greatest relative size in the song system of duetting birds compared to non duetting species. PMID- 4041848 TI - Sites of D-[3H]aspartate accumulation in mouse cerebellar slices. AB - Slices of mouse cerebellar vermis, cut in the parasagittal plane, were incubated for various times (up to 3 h) in the presence of 1 microM D-[3H]aspartate, a non metabolized substrate for the glutamate/aspartate carrier in brain tissue. Light microscopic autoradiography indicated that in regions away from the cut edges of the slices the amino acid accumulated in glia and granule cells. Relatively few grains were seen over Purkinje, Golgi, stellate and basket cells or over white matter. Grain counts over the granule cell layers in the middle parts of the slices indicated that after short (15 min) exposures to the labelled substrate, non-granule cell areas (which included glia) contained, on average, slightly more grains than granule cells but with longer exposures (1.5 and 3 h) the relative grain density over granule cells became much higher, possibly because glial uptake prevents D-[3H]aspartate gaining access to neuronal sites in adequate amounts during short incubations and/or because the longer incubations allow time for retrograde migration of the label from parallel fibre terminals to occur. The demonstration of selective uptake of D-[3H]aspartate into granule cells contrasts with previous autoradiographic results (possible reasons for which are discussed) and supports the notion that L-glutamate is the transmitter of granule cells. The results also have a bearing on the importance of the metabolic compartmentation of glutamate in relation to its proposed transmitter role. PMID- 4041849 TI - The identification of thalamocortical axon terminals in barrels of mouse Sml cortex using immunohistochemistry of anterogradely transported lectin (Phaseolus vulgaris-leucoagglutinin). AB - The anterograde transport and immunohistochemical demonstration of the lectin, Phaseolus vulgaris-leucoagglutinin (PHA-L) has been used to label thalamocortical axon terminals in barrels of mouse SmI cortex. The reaction product is visible with both the light and electron microscopes so that the distribution of axons and the types of synapses they form can be determined. PMID- 4041850 TI - Sexual dimorphism of glucocorticoid binding in rat brain. AB - Glucocorticoids bind with high affinity to intracellular receptors located in high density within discrete regions of the rodent and primate brain. The binding of [3H]corticosterone was compared in the brains of male vs female rats. The number and affinity of cytosol receptors in the hippocampus and hypothalamus were examined in vitro. The cytosolic binding capacity of the hippocampus is greater in the female than in the male. This difference in binding capacity is not dependent on the presence of gonadal steroids: the effect of gonadectomy was not significant for either sex. The difference is not due to transcortin since the binding capacity of [3H]dexamethasone is also greater in the female hippocampus. Receptor affinity in the female hippocampus is half that of the male value. In the hypothalamus, the dimorphism is in the opposite direction: the number of [3H]corticosterone cytosolic binding sites was found to be greater in the male. The male hypothalamus also showed a greater affinity for [3H]corticosterone than did the female. Ovariectomy increased the number of binding sites in the female hypothalamus. In vivo nuclear uptake of a tracer dose of [3H]corticosterone was determined in animals having intact gonads. The percent of tissue [3H]corticosterone present in cell nuclei from 4 brain regions, including the hippocampus and hypothalamus, was calculated per unit DNA. The concentrations of [3H]corticosterone in nuclei relative to tissue homogenates were higher in females than males for the 4 brain regions, but not for the pituitary or liver. The data are interpreted as suggesting that glucocorticoid secretion under basal conditions and during stress may differentially effect specific brain structures in male vs female rats. PMID- 4041851 TI - Myotrophic effects on denervation atrophy of hindlimb muscles of mice with systemic administration of nerve extract. AB - Atrophy was assessed in denervated hindlimb muscles of adult mice which either were not otherwise treated or received daily intraperitoneal injections of extract of rats' sciatic nerves. After 7 days, the denervated muscles of injected animals exhibited significantly smaller decreases in wet weight, total protein and cross-sectional areas of muscle fibers relative to innervated contralateral control muscles. The effects of denervation and nerve extract on different muscles varied. PMID- 4041852 TI - Decrease in histamine turnover in the brain of spontaneously hypertensive rats. AB - Histamine (HA) turnover rate in the brain of spontaneously hypertensive rats (SHR) was determined by the accumulation of telemethylhistamine after pargyline treatment. The values in these SHR were lower than in the Wistar Kyoto rats, particularly in the hypothalamus and brainstem. However, chronic treatment with L histidine had no effect on the development of hypertension in the SHR. The functional significance of the decreased HA turnover in SHR is discussed in relation to the pathogenesis of hypertension. PMID- 4041853 TI - Banding of rubro-olivary terminations in the principal inferior olivary nucleus of the chimpanzee. AB - An electrolytic lesion centered just dorsal to, and grazing the superior surface of, the rostral red nucleus (RNr) was produced stereotactically in a single chimpanzee. Perikarya of the ipsilateral RNr exhibited retrograde cell changes, demonstrating interruption of its efferent fibers. The degenerated rubro-olivary tract was followed in silver impregnated material to the ipsilateral compact part of the pedunculopontine nucleus, pontine reticular formation and inferior olivary complex. Within the inferior olivary complex, terminations were banded and restricted to the principal subnucleus. PMID- 4041854 TI - Norepinephrine stimulates serotonin secretion from rat pineal glands, in vitro. AB - The purpose of this study was to determine if serotonin (5-HT) is secreted by the pineal gland and also to define the parameters of its secretion. After radiolabelling the endogenous 5-HT pool, individual pineal glands were placed within perifusion chambers and stimulated with norepinephrine (NE). [3H]5-HT was rapidly released within 1 min of stimulation and secretion continued throughout the period of exposure to NE. The findings suggest that 5-HT, in addition to melatonin, is a hormone of the pineal gland. PMID- 4041855 TI - A metabolic profile of the rat caudate microvasculature: a histochemical study. AB - Arterioles of the rat caudate nucleus were examined histochemically to determine their metabolic profile. These microvessels appear capable of aerobic and anaerobic metabolism with a potential for nucleic acid and protein synthesis. Little intramural lipid storage occurs and any fatty acids utilized are provided via the blood supply. Likewise, glycogen is not seen in the arteriolar wall and may be rapidly turned over as a substrate for anaerobic metabolism. PMID- 4041856 TI - Carrier-mediated KCl accumulation accompanied by water movements is involved in the control of physiological K+ levels by astrocytes. AB - Potassium accumulation and water transport into mouse astrocytes in primary cultures were investigated when external potassium was increased from 3 to 12 mM. The intracellular potassium content increased by 63% within 50 s of such a change. The increase consisted of a ouabain- and furosemide-sensitive component, both contributing in about the same amounts. Experiments with altered ion composition revealed that the furosemide-sensitive component consisted of a KCl accumulation. Water moved into the astrocytes without delay after such an external K+ increase and increased the cell water by 27%. This water increase was abolished in solutions with reduced Cl- and during application of furosemide. Thus, these results on a KCl uptake accompanied by water movements into astrocytes suggest a potential mechanism by which glial cells in situ can regulate external K+ levels. PMID- 4041857 TI - Differences in some of the metabolic properties of mitochondria isolated from cerebral cortex and olfactory bulb of the rat. AB - The metabolic properties of mitochondria from rat cerebral cortex and olfactory bulb were investigated. The pyruvate-supported oxygen uptake rates by olfactory bulb mitochondria were significantly lower than those by cerebrocortical mitochondria. This is consistent with the differences in pyruvate dehydrogenase complex activities between these mitochondrial preparations. Pyruvate dehydrogenase kinase, NAD-linked isocitrate dehydrogenase, and hexokinase activities in olfactory bulb mitochondria were significantly lower than those in cerebrocortical mitochondria. However, NADP-linked isocitrate dehydrogenase, and NAD-linked and NADP-linked glutamate dehydrogenase activities in olfactory bulb mitochondria were significantly higher than those in cerebrocortical mitochondria. The differences between these two mitochondrial preparations in terms of the activities of these energy-metabolizing enzymes reflect the differences detected in the homogenates of these regions. PMID- 4041858 TI - Pulmonary edema and death induced by sinoaortic denervation in fastigial nucleus lesioned rats. AB - When adult male rats with lesions of the cerebellar fastigial nucleus were subjected to sinoaortic denervation and instrumented for aortic pressure recording, their elevated mean arterial pressure was found to rise no higher than that of rats with sinoaortic denervation alone; however all of the doubly operated rats died or became moribund within 4 days. Pulmonary edema and gastric ulcers were frequently seen. When the order of operations was reversed, all animals survived. The possible mechanism and involvement of other brain nuclei, catecholamines and vasopressin in these pathological changes is discussed. PMID- 4041859 TI - Unidirectional interaction between flurothyl seizures and amygdala kindling. AB - In this report, the interaction between flurothyl convulsions and electrical kindling of the amygdala was investigated. Three flurothyl convulsions decreased the afterdischarge threshold of the amygdala and enhanced the rate of development of electrical kindling without affecting the intensity of postictal refractoriness. On the other hand, 3 generalized kindled convulsions did not alter the flurothyl convulsive threshold. The data suggest that the influence of generalized convulsions on future seizure susceptibility may depend on the agents used to induce the convulsions. PMID- 4041860 TI - Protein synthesis requirement for the formation of synaptic elements. AB - The formation of synapses in cell cultures of rat cerebellum was examined in the presence of the protein synthesis inhibitor cycloheximide. First, cell survival in the presence of 25 micrograms/ml cycloheximide was determined by phase contrast microscopy, trypan blue exclusion, total protein and uptake of [3H]gamma aminobutyric acid (GABA). Neurons with 24 h incubation in cycloheximide appeared normal with little cell death, but by 48 h incubation the first signs of cell death were found. Some viable neurons were still found in cultures incubated continuously in cycloheximide for 72 h. Normally, the number of synapses seen in cerebellar cultures with the electron microscope shows an increase during the first several weeks in culture. However, the number of synapses in cultures treated with cycloheximide decreased, indicating that inhibition of protein synthesis at least partially inhibited synaptogenesis. Cycloheximide also inhibited the maintenance of synapses already formed as seen by the decrease in the number of synapses from the time the cycloheximide was added. To determine the sensitivity of the forming presynaptic element to cycloheximide, the development of apparent presynaptic elements was investigated. In cultures treated with polylysine-coated sepharose beads, neurites grew and formed apparent presynaptic elements with the bead taking the position of the postsynaptic element. Cultures pretreated with cycloheximide for 1 h followed by 24 h incubation with both cycloheximide and coated beads showed a normal number of apparent presynaptic elements. The first decrease in numbers was seen after 12 h preincubation and 12 h incubation with both cycloheximide and coated beads. Even after 72 h continuous incubation some apparent presynaptic elements could be formed although at reduced levels. Results presented here suggest that continuous protein synthesis is not necessary for the formation of the presynaptic element, but that active protein synthesis is required for neurons to form and maintain postsynaptic elements. PMID- 4041861 TI - Circannual variations of GABA content in cytosolic and crude synaptosomal fractions in some brain areas of the European hamster. AB - In the European hamster, Cricetus cricetus, a common hibernator, over a year, the gamma-aminobutyric acid (GABA) content has been followed, in the cytosolic and crude synaptosomal fractions of the olfactory bulbs, hypothalamus and cerebellum. In these 3 areas, the GABA content shows circannual variations of endogenous origin: in this period, in both fractions two peaks can be observed, at the beginning of spring and in autumn. These circannual variations do not follow the circannual variation of food intake or body weight. PMID- 4041862 TI - Overshoot of oxygen pressure in post-hypoxic brain tissue: a re-evaluation. AB - Tissue oxygen pressure (ptO2) was measured with noble metal microelectrodes in hippocampal slices in vitro. During hypoxia, the ptO2 at 100 micron depth fell rapidly to less than 20 mm Hg. During reoxygenation, large transient ptO2 increases above normoxic values were observed. These data demonstrate that ptO2 'overshoots' occur independently of in situ posthypoxic hyperemia and may reflect pathologic chemical reactions in brain tissue during reoxygenation. PMID- 4041863 TI - Behavioural responses to electrical stimulation of the nucleus of the tractus solitarius of the cat. AB - Electrical stimulation of the region of the nucleus tractus solitarius (NTS) significantly reduced both the lever-pressing rate for substantia nigra self stimulation and the food-consumption in food-deprived cats. In a shuttle box the cats showed no tendency toward shuttling in response to NTS stimulations with randomly varied stimulus intensities. In contrast with these effects, stimulation to nucleus reticularis paramedianus yielded an aversive effect. PMID- 4041864 TI - 1H-NMR spectra of rat synaptic plasma membranes: effect of temperature and comparison with fluorescence polarization. AB - 1H-NMR spectra of rat synaptic plasma membranes obtained over the temperature range of 24-46 degrees C are presented. The data illustrate that a transition occurs from a more ordered to less ordered state at approximately 37 degrees C. This phenomenon was not related to using D2O as the solvent and was replicated, although with less sensitivity, using fluorescence polarization methodology. PMID- 4041865 TI - Selective labeling of 5-HT1A and 5-HT1B binding sites in bovine brain. AB - Drug interactions with serotonin(1A) 5-HT1A and serotonin(1B) (5-HT1B) binding sites were analyzed in bovine brain membranes. 5-HT1A binding sites were directly labeled with [3H]8-hydroxy-2-(di-n-propylamino)-tetralin (8-OH-DPAT) in bovine hippocampal membranes. 5-HT1B binding sites were labeled by [3H]5-HT in bovine striatal membranes where less than 15% of specific binding sites are sensitive to nanomolar concentrations of 8-OH-DPAT. Each of the 12 agents tested was more potent at the 5-HT1A than 5-HT1B binding site. 5-HT, bufotenine, N,N dimethyltryptamine (DMT) and quipazine were only slightly more potent at the 5 HT1A binding site. By contrast, 8-OH-DPAT, TVX Q 7821 and buspirone were significantly more potent at [3H]8-OH-DPAT binding sites in bovine hippocampus than at [3H]5-HT binding sites in bovine striatum. These findings suggest that 5 HT1A, and 5-HT1B binding sites have distinct pharmacological profiles and can be directly labeled with appropriate [3H]ligands in specific brain regions. PMID- 4041866 TI - Lack of sexual dimorphism in steroid accumulation in vocal control brain regions of duetting song birds. AB - Tritiated testosterone was injected into bay wrens (Thryothorus nigricapillus), a neotropical species in which the female sings a complex song in intricately timed vocal duets with males. Autoradiographic analysis indicated that male and female wrens have the same proportion of cells labeled by testosterone or its metabolites in two brain regions involved in song: the caudal nucleus of the ventral hyperstriatum (HVc) and the magnocellular nucleus of the anterior neostriatum (MAN). This contrasts with the zebra finch, a species in which only the males sing: a considerably greater proportion of male zebra finch cells in HVc and MAN are labeled than in females. This suggests that female birds that produce complex vocalizations have evolved neural song control systems that are extremely similar to those of males in steroid hormone sensitivity. PMID- 4041867 TI - The relationship between cortical electrical activity and regional cerebral glucose metabolic rate in rats exposed to 3 atmospheres absolute oxygen. AB - The regional cerebral metabolic rate for glucose (rCMRgl) was autoradiographically measured in conscious rats during 180-210 min of exposure to 3 atmospheres absolute oxygen (ATA O2), 3 ATA N2-O2 normoxia and air at 1 ATA. The exposure time and oxygen pressure in the present study were purposely matched to a parallel project in human subjects. The electrocorticogram (ECoG) was continuously recorded throughout the exposure. According to the ECoG responses, the oxygen-exposed rats fell into two categories: 'resistant' ones, those without changes in ECoG throughout the exposure; and 'sensitive' rats, those with changes in EcoG before or during the rCMRgl measurements. The observed ECoG changes were increased slow wave activity in the delta range, which was in some cases followed by paroxysmal electrical discharges. No changes in rCMRgl were observed in oxygen exposed 'resistant' rats as compared to air breathing or N2-O2 normoxic rats at 3 ATA. However, in the 'sensitive' rats there were increases in rCMRgl in 8 of the 28 neuroanatomical structures examined as compared to the air breathing and 3 ATA normoxic controls. It is concluded that the increase in rCMRgl are related to the onset of the oxygen-induced preconvulsive changes in ECoG. PMID- 4041868 TI - A reappraisal of rat motor cortex organization by intracortical microstimulation. AB - The organization of the motor cortex was reinvestigated with intracortical microstimulation, in light-anaesthetized (ketamine) rats. A posterolateral (PL) vibrissae area was found in addition to the rostral one, and blinks of the contralateral eyelids were elicited from a part of this PL area. Several cortical representations such as neck or tail were largely overlapping with neighbouring areas. Vegetative effects (mainly myosis and swallowing) were obtained from a medial cortical strip. Within the PL vibrissae area, a topical arrangement related to the vibrissal rows was observed, whereas in the leg areas, no individual representation of muscles could be evidenced. These results are compared with the maps previously published, and discussed in terms of specificity, musculotopy and overlapping of motor areas. PMID- 4041869 TI - Regulatory role of cysteine dioxygenase in cerebral biosynthesis of taurine. Analysis using cerebellum from 3-acetylpyridine-treated rat. AB - The effect of 3-acetylpyridine (3-AP) administration on the biosynthesis of taurine in the rat brain has been studied. Treatment with 3-AP induced a significant decrease in the cerebellar contents of taurine and its metabolic precursors, cysteine sulfinic acid (CSA) and cysteic acid (CA), as well as a selective degeneration of climbing fibers in the molecular layer of the cerebellum. It was found that the activity of cerebral cysteine dioxygenase, the enzyme catalyzing the formation of CSA from cysteine, consisted of two systems with low and high Km values. The 3-AP-induced attenuation of cysteine dioxygenase activity with a low Km value was noted only in the cerebellum, while that with a high Km value was detected not only in the cerebellum but also in other brain areas such as the medulla oblongata, striatum and cerebral cortex. In contrast, no alteration in the activity of cysteine sulfinic acid decarboxylase (CSD) was observed in any brain areas examined following the administration of 3-AP. Furthermore, it was found that essentially no cystamine as well as a very low activity of cysteamine dioxygenase is present in the brain. The present results suggest that taurine in the brain is synthesized from cysteine, mainly by the CSA and CA pathways, and the observed decline of cerebellar taurine in 3-AP-treated rats may be due to an attenuation of the biosynthesis, possibly at the step of cysteine dioxygenase. A possible regulatory role of cysteine dioxygenase with a low Km value in the biosynthesis of cerebral taurine is also suggested. PMID- 4041870 TI - Ascending reticular activating system in the rat: a 2-deoxyglucose study. AB - The autoradiographic [14C]2-deoxyglucose (2-DG) method was used to map ascending pathways which are influenced by arousing electrical stimulation of the midbrain reticular formation (RET) in alert rats. The major finding was that RET stimulation produces selective patterns of metabolic activation and suppression in discrete brain regions. The regions activated were limited to specific intralaminar, medial and anterior thalamic nuclei, and to the entire auditory system. Conversely, a large suppression of 2-DG uptake was observed in most of the cerebral cortex, limbic and extrapyramidal structures, whereas at the same time some brain regions were left unaffected. Striking similarities were found between the functional pathways affected differentially by RET stimulation and well-defined cholinergic pathways which originate in the midbrain tegmentum. Structures which showed metabolic activation are part of the dorsal cholinergic pathway, whereas the regions suppressed are part of the ventral cholinergic pathway and its higher-order projections. The results support the conclusion that cholinergic pathways represent the thalamic and extrathalamic divisions of the reticular activating system. Our observations provide the first anatomical demonstration that RET stimulation has widespread and differential effects on cerebral metabolism. They also support the concept that arousing electrocortical desynchronization involves reticular activation of thalamocortical neurons, which in turn have widespread suppressive influences on cortical metabolism. PMID- 4041871 TI - Effect of chronic lithium on cholinergically mediated responses and [3H]QNB binding in rat brain. AB - Lithium (Li) has been previously reported to increase acetylcholine turnover and release in rat brain and to potentiate the neurotoxicity of cholinergic agents. We studied the effect of chronic Li administration, alone and in combination with the muscarinic antagonist, scopolamine, on two cholinergically-mediated responses and on muscarinic cholinergic receptor (MCR) binding in rat brain. Administered separately, Li and scopolamine enhanced the cataleptic and hypothermic responses to pilocarpine; combined administration resulted in an additive effect on both these measures. [3H]Quinuclidinyl benzilate ([3H]QNB) binding was increased by Li in the corpus striatum but not in the cortex, hippocampus and hypothalamus. Scopolamine increased [3H]QNB binding in the striatum, cortex and hippocampus; Li and scopolamine effects on striatal MCR were not additive. Contrary to a previous report, antagonist-induced MCR supersensitivity was not prevented by concurrent Li administration in any of the brain areas studied. The additive effect of Li and scopolamine on pilocarpine-induced catalepsy and a trend in this direction for pilocarpine-induced hypothermia suggest that the actions of the two agents to enhance cholinergically mediated responses may be achieved by different mechanisms. Supersensitive responses following scopolamine may be attributed to antagonist-induced up-regulation of postsynaptic muscarinic receptors as demonstrated in the binding studies. The effects of Li to enhance cholinergically mediated catalepsy and hypothermia are interpreted as extending previous reports that Li stimulates brain cholinergic function by a presynaptic increase in acetylcholine turnover and release. PMID- 4041872 TI - ATP-dependent [3H]Met-enkephalin uptake by bovine adrenal chromaffin granule membrane. AB - Uptake of [3H]Met-enkephalin by purified chromaffin granule membrane isolated from bovine adrenal medulla was investigated. Addition of a single divalent cation, such as Mg2+ or Ca2+, did not affect the uptake. The presence of 3 mM ATP in the incubation medium stimulated the uptake to two times that of the control. The same stimulation effect was also found in the presence of ATP plus a single divalent cation. The ATP-dependent uptake reached its half-maximal level within 5 min after initiation of the reaction at 25 degrees C, and reached a plateau within 10 min. The apparent Km for [3H]Met-enkephalin uptake by the chromaffin granule membrane was about 2.3 X 10(-6) M. GTP, CTP, UTP and ADP did not stimulate enkephalin uptake. Several calcium inhibitors such as trifluoperazine, verapamil and 3,4,5-trimethoxybenzoic acid 8-(N,N-diethylamino)octylester (TMB-8) markedly inhibited enkephalin uptake. The inhibition exceeded 80%, although these chemicals inhibited Ca2+-ATPase activity in chromaffin granule membrane only 30% under the same conditions. Ethyleneglycol-bis-(beta-aminoethylether)N,N' tetraacetic acid (EGTA), at 3 mM also inhibited uptake about 30%. The results indicate that uptake of Met-enkephalin by chromaffin granule membrane ghosts was driven not only by ATPase activity, but also by some other Ca2+-ATP-mediated mechanism(s). PMID- 4041873 TI - Localization of the spinal accessory motoneurons in the cervical cord in connection with the phrenic nucleus: an HRP study in cats. AB - The localization of the spinal accessory motoneurons (SAMNs) that innervate the accessory respiratory muscles, the sternocleidomastoid (SCM) and trapezius (TP) muscles, was identified in the cat using the horseradish peroxidase (HRP) method. In the cases of HRP bathing of the transected spinal accessory nerve (SAN), HRP labeled motoneurons were observed ipsilaterally from the C1 to the rostral C6 segments of the spinal cord. Labeled neurons were located principally in the medial and central regions of the dorsomedial cell column of the ventral horn in the C1 segment, in the lateral region of the ventrolateral cell column in the C2 C4 segments, between the ventrolateral and ventromedial cell columns in the C5 segment and in the lateral region of the ventromedial cell column in the C6 segment. In the cases of HRP injection into either SCM or TP muscles, labeled SCM motoneurons were found in the C1-C3 segments of the spinal cord and labeled TP motoneurons were chiefly localized more caudally within the spinal accessory nucleus. The present study revealed that, in the C5 and C6 segments, the SAMNs have a very similar topographic localization to the phrenic nucleus in the ventral horn. This finding implicated the functional linkage of the SAMNs with the phrenic motoneurons in particular types of respiration. PMID- 4041874 TI - Neuronal damage in the rat retina after chronic stress. AB - Long-term exposure to escapable foot shock has been used to determine if chronic stress influences neuronal cell death in the retina of albino and pigmented rats. Histopathologic and morphometric approaches analyzed changes in photoreceptors and neurons of the bipolar and ganglion cell layers of the retina. Albino Fischer rats when exposed to chronic stress for 4-8 h daily for 1 week to 6 months, developed severe retinal damage, as compared to unstressed control retinas, with reduction in photoreceptor and bipolar neurons, particularly in the superior central retina. The damage was observed in male and female rats, but males appeared to be more susceptible to the influence of stress than female animals. Ganglion cells were unaffected. Photoreceptor destruction did not occur in Long Evans pigmented rats under identical experimental conditions. The results suggest that: input of the sensory stimulus, light, to the retina of stressed rats augmented neuronal damage and might be required for its initiation; and hormones and/or neurotransmitters associated with long-term chronic stress might be related to increased neuronal cell death in the mammalian retina. PMID- 4041875 TI - Locus coeruleus unit activity in freely moving cats is increased following systemic morphine administration. AB - Contrary to previous reports of morphine's depression of locus coeruleus (LC) unit activity in anesthetized animals, acute administration of morphine (0.5, 2.0 or 4.0 mg/kg, i.p.) did not decrease the unit activity of noradrenergic neurons in the area of the LC of freely moving cats. In fact at the higher doses examined (2.0 and 4.0 mg/kg) morphine significantly increased unit activity. Naloxone (1 mg/kg, i.p.) administration reversed the increase in unit activity produced by morphine. When these same studies were conducted in cats first anesthetized with chloral hydrate, morphine produced a significant decrease in unit activity in a naloxone-reversible manner. These results suggest that previous reports of systemic morphine's depression of LC unit activity may be at least partially attributable to an interaction with anesthesia. Morphine's multiplicity of actions upon the LC is discussed. PMID- 4041876 TI - Glial and axonal development in optic nerve of myelin deficient rat mutant. AB - Development of glial cell lines and axons is reported for the optic nerve of the myelin deficient rat mutant, md, 3-46 days postnatally. In mutants, optic nerves do not increase in area after 16 days of age whereas, in normal rats, they enlarge through 46 days of postnatal life. The density of glial cells, determined in cross-sections, is similar in md and normal littermates through 19 days postnatally. Thereafter, glial densities are greater in the mutant. Nonetheless, total glial counts are reduced in md as compared to the normal, because cross sectional areas and lengths of mutant nerve 30-46 days after birth are smaller than those of age-matched, normal littermates. Differential counts of glial cells, made by ultrastructural criteria, show that md optic nerves contain abnormal, vacuolated, immature oligodendroglia from the third postnatal day. Furthermore, oligodendrocytes are reduced in number in older mutants; they constitute 1% of optic nerve neuroglia at 46 days. Astrocytic numbers are increased in relative, not in absolute, terms from 19 days, and microglial numbers are greater than normal in the oldest mutants. Reactive microglia, containing large cytoplasmic lipid droplets, constitute 4-8% of the glia of md nerve 19-46 days postnatally. Mean axonal areas are similar in normal rats and mutants at 19 and 43-46 days of age. However, mitochondrial density is greater in md axons 19 days after birth and mean areas of axonal mitochondria are significantly larger in 43-46 day mutants than in age-matched, normal littermates. Additionally, the percent area of axoplasm occupied by mitochondria is increased in md at both 19 and 43-46 days of age. The myelination defect in md appears to be due primarily to an oligodendroglial abnormality which precedes the normal age of onset of myelination. Astrocytic and microglial changes are secondary. Axonal enlargement proceeds normally over 46 days of postnatal life. Overall, the data do not provide definitive support for an axonal basis for the myelination defect, although measurable differences in axonal mitochondria between mutants and normals are demonstrable and qualitative abnormalities do occur in the axons of the mutant. PMID- 4041877 TI - Laser-induced somatosensory evoked potentials: evidence of photosensitivity in peripheral nerves. AB - Irradiation of the skin overlying the median nerve at the wrist in humans with a low power (1 mW; 632.5 nm) helium-neon laser produced a somatosensory evoked potential obtained at Erb's point. This evoked potential had a latency equal to that observed after electrical stimulation of the same nerve. Prolonged exposure to laser (20 min, 3.1 Hz) resulted in a large (10-90%) decrease in the amplitude of the electrical evoked potential. Since this laser produces no detectable thermal change, the results imply that photochemical reactions alter neuronal activity. PMID- 4041878 TI - Induction of epileptiform activity in hippocampal slices by trains of electrical stimuli. AB - In this paper we present an in vitro model of epileptogenesis based on electrical stimulation rather than pharmacological or ionic manipulations. Hippocampal slices given a series of stimulus trains similar to those used in kindling exhibited 3 types of epileptiform activity in CA3: afterdischarges immediately following the trains; spontaneous bursts of multiple population spikes; and bursts triggered by single stimuli. The afterdischarges and spontaneous bursts may be comparable to those seen in vivo during kindling; also, the progression of these features in this model was similar to their progression during kindling. All epileptiform activities were long-lasting, persisting for up to 3.5 h following the last train. This stimulus train-induced population bursting should be valuable as an acute model of hippocampal epileptogenesis, and may also help elucidate hippocampal participation in the kindling process. PMID- 4041880 TI - Electrophysiological evidence that the mediodorsal nucleus of the thalamus is a relay between the ventral pallidum and the medial prefrontal cortex in the rat. AB - The neural connections from the ventral pallidum (VP) through the mediodorsal nucleus of the thalamus (MD) to the medial prefrontal cortex (MPC) were investigated. Extracellular recordings were made from 219 neurons in the medial and lateral portions of the MD and the VP and the MPC were stimulated. The most frequent response to VP stimulation was inhibition and inhibition preceded by excitation. Also, the most frequent response of MD units to MPC stimulation was inhibition and inhibition preceded by excitation. Nineteen of 26 MD units, activated antidromically by MPC stimulation, responded orthodromically to VP stimulation. The most frequent orthodromic response of these MD output neurons was inhibition and inhibition preceded by excitation. GABA iontophorized onto MD neurons reduced their rate of discharge. GABA and picrotoxin iontophorized onto MD neurons did not influence the inhibitory or excitatory responses to VP stimulation. These electrophysiological results support previous anatomical findings of connections between the VP and the MPC by way of the MD. MD output neurons to the MPC receive mostly inhibitory inputs from VP afferents. A high proportion of MD neurons respond orthodromically to both VP and MPC stimulation, suggesting the convergence of synaptic inputs from these structures to the same MD units. PMID- 4041879 TI - Neurophysiological analysis of the development of endocrine and hypertensive reactions in prolonged emotional stress. AB - The model of immobilization stress with aperiodic foot shock (FS) was used to study the effect of a prolonged emotional stress on the functional condition of cortical and subcortical structures (hypothalamic and reticular structures in particular) in EEG activity and to elucidate their role in the development of endocrine and hypertensive reactions. It is shown that the development of hypertensive reactions in animals is stipulated by dynamic changes in the functional condition of the CNS, particularly in the hypothalamic neuroendocrinal control mechanism and reticular formation of the midbrain, which can be conditionally subdivided into 3 stages. The first is characterized by the emergence of short-time cycles of the hypersynchronized activity of slow waves in the cortical and subcortical mechanism, which is accompanied by adaptive hormonal secretion and transient effects of vascular reactions to FS; in the meantime neither neuroendocrinal nor blood pressure (BP) self-regulation mechanisms are impaired. The second stage is characterized (3-4 days after the beginning of the exposure) by the development of 'persistent' excitation in the CNS and the stabilization of a high level of hormones in the blood. Vascular reactions to FS are extremely prolonged ones; in intervals between FS applications BP fails to return to initial values. The third stage (1 month after cessation of experiments) is characterized by normal background EEG-activity in cortical subcortical structures, normal indices of hormonal homeostasis but high level of BP. In response to 'repeated' stress, on the first experimental day, prolonged hypersynchronization of slow waves in cortical-subcortical structures occurred while BP reactions to FS were also prolonged and high hormonal secretion was observed. The data obtained suggest the high reactivity of reticular-hypothalamic structures which determine primarily the characteristics of both vascular and hormonal reactions that could be understood to be due to the result of previous experience (the first stage of stress). PMID- 4041881 TI - Hypothalamic projections to the ventral medulla oblongata in the rat, with special reference to the nucleus raphe pallidus: a study using autoradiographic and HRP techniques. AB - Hypothalamic descending projections to the medullary ventral surface were studied autoradiographically in the rat. A small amount of [3H]leucine was injected unilaterally into various parts of the hypothalamus by air pressure. Abundant and characteristic terminal labelings were observed bilaterally in the nucleus raphe pallidus, the ventral surface of the pyramidal tract and the nucleus interfascicularis hypoglossi, after injections into the dorsal posterior hypothalamic area caudal to the paraventricular hypothalamic nucleus. Conspicuous, but less numerous labelings were observed in the nucleus raphe obscurus and the ipsilateral raphe magnus. After an injection of [3H]leucine into the hypothalamus and injections of horseradish peroxidase (HRP) into the spinal cord in the same animal, silver grains were densely distributed around HRP labeled neurons in the nucleus raphe pallidus including the nucleus interfascicularis hypoglossi. The present results suggest that the dorsal posterior hypothalamic area projects directly to the spinal-projecting neurons of the nucleus raphe pallidus. PMID- 4041882 TI - Cholecystokinin (CCK) gene-related peptides: distribution and characterization of immunoreactive pro-CCK and an amino-terminal pro-CCK fragment in rat brain. AB - An antiserum specific for the amino terminus of pro-CCK detects 3 major peptides in rat brain with molecular weights of 13,000, 8000 and 2700 daltons. These peptides are abundant both in CCK terminal-field regions and regions rich in CCK perikarya. The two high molecular weight peptides probably represent CCK precursor molecules. The smaller peptide is probably the amino-terminal fragment of pro-CCK and may be stored and released along with CCK-8, and have a potential role in synaptic transmission. PMID- 4041883 TI - Increase in the threshold of a nociceptive test induced by naloxone in morphine tolerant rats. AB - The effects of various doses of naloxone (3-1000 micrograms/kg i.v.) on the vocalization threshold elicited by pressure on the paw were evaluated in rats chronically treated with high doses of morphine. In addition to the well known precipitation of withdrawal induced by naloxone, an unexpected dose-related increase in the vocalization threshold was observed. PMID- 4041884 TI - Unilateral and bilateral cortical spreading depression interferes with radial maze performance in rats. AB - Seven rats with implanted cortical electrodes were trained in a 12-arm radial maze to asymptomatic performance (1.38 errors per trial). Single waves of cortical spreading depression (CSD) were elicited by application of cathodal current to the parieto-occipital cortex and monitored by suppression of callosal responses in the frontal cortex. Bilateral CSD elicited before the trial caused a small increase of error incidence in choices 1-6 but did not affect accuracy of choices 7-12. Bilateral CSD between choices 6 and 7 increased error incidence in the second half of the trial from 1.33 to 2.84, i.e. almost to the chance level of 3.0. Unilateral CSDs elicited before the first half of the trial in one hemisphere and in the same or in the contralateral hemisphere before the second half of the trial caused similar deterioration of performance in choices 7-12 (2.4 and 2.1 errors, respectively). It is concluded that the CSD effects have both proactive and retroactive components and that the working memory record is not lateralized at the cortical level. PMID- 4041885 TI - Autoradiographic determination of catechol estrogen binding sites in brain, pituitary and uterus. AB - The anatomical pattern of nuclear binding of 2-OH[6,9-3H]estradiol ([3H]2-OHE2) in brain, pituitary and uterus have been studied autoradiographically. Autoradiograms of forebrain, pituitary and uterus show nuclear concentrations of radioactivity in certain cells. This nuclear concentration is abolished when unlabelled 2-OHE2 or E2 was injected prior to the injection of [3H]2-OHE2. In the brain nuclear labelling is observed in the septal-preoptic region, in the anterior hypothalamic area, and in the central hypothalamic area. Some estrogen sensitive nuclear groups, such as lateral septum and hippocampus, do not show accumulation of radioactivity. In the uterus, luminal and glandular epithelium, stromal cells and muscle cells are labelled. A comparison of the quantitative nuclear uptake of radioactivity and of the different time intervals after the injection of different doses shows similar uptake of nuclear radioactivity. This is comparable to data obtained after [6,7-3H]estradiol ([3H]E2) injection. The results provide clear evidence for nuclear binding of catechol estrogens of the same magnitude as [3H]E2 after in vivo treatment. PMID- 4041886 TI - Species-specific charge forms of phenylethanolamine N-methyltransferase. AB - Isoelectric points (pI) of phenylethanolamine N-methyltransferase (PNMT) from two species, cow and rat, were determined by chromatofocusing. Bovine PNMT has 5 different charge isozymes ranging from 5.4 to 6.2. In contrast, rat PNMT has only a single charge form of pI 4.8. There is no common isoelectric point of PNMT from both species and there is no tissue variation in the isoelectric point. PMID- 4041887 TI - Differences in density and distribution of surface glycoconjugates between normal and dystrophic mouse Schwann cells detected by statistical analyses of lectin ferritin binding. AB - Cultures of Schwann cells and neurons from dorsal root ganglia of normal (C57bl/6J +/+) and dystrophic (C57bl/6J dy2j/dy2j) mice were labeled with wheat germ agglutinin (WGA) and Ricinus communis agglutinin (RCA-I) conjugated to ferritin. Statistical methods were used to compare the regional densities and distribution characteristics of lectin binding in these two types of Schwann cells, which differ in their capacities to ensheath and myelinate axons in vivo and in cultures. Regional variations in lectin binding densities and distributions were observed in both types of Schwann cells. WGA-ferritin was bound at lower densities in dystrophic mouse Schwann cells than in corresponding regions of normal cells. In both normal and dystrophic cells, WGA-ferritin was distributed at greater densities on the free surfaces of Schwann cells than on the substrate-associated surfaces. WGA-ferritin was clustered in all regions of both normal and dystrophic mouse cells. RCA-ferritin densities did not differ significantly between corresponding regions of normal and dystrophic mouse Schwann cells. However, in normal mouse Schwann cells, the density of RCA ferritin was significantly greater in the thinner, peripheral processes of Schwann cells than in thicker perinuclear regions of the cells. Differences in the degree of RCA-ferritin clustering were also detected between normal and dystrophic Schwann cells. These results indicate that regional differences in the density and distributions of cell surface glycoconjugates occur in Schwann cells of normal and dystrophic mice. PMID- 4041888 TI - Rat brain synthesizes two 'vitamin D-dependent' calcium-binding proteins. AB - Two proteins from rat brain reacting against anti-chick intestinal vitamin D dependent calcium-binding protein were characterized in terms of their mobility on sodium dodecyl sulfate-polyacrylamide gel electrophoresis and their molecular size. The proteins were present in the isolated cytoplasm and were produced following translation of brain mRNA in the rabbit reticulocyte lysate system. Their apparent molecular weight was 29,000 and 27,000 daltons whereas rat kidney contained only one protein cross-reacting with this antiserum and with a molecular weight of 27,000 daltons. PMID- 4041889 TI - Effect of tilt on the response of neuronal activity within the cat vestibular nuclei during slow and constant velocity rotation. AB - The responses of neurons sensitive to static tilt in the vestibular nuclei were examined in decerebrate cats during slow and constant velocity rotations about an axis tilted at various angles from the vertical. During any 360 degrees rotation, each unit showed a modulation of their firing rate, with a position-dependent maximum and minimum. Changes in amplitude of head displacement from 5 degrees to 25 degrees decreased the response gain of the units without affecting the locations of the discharge maxima and minima. PMID- 4041890 TI - Muscarinic mobilization of choline in rat cerebral cortex does not involve alterations of blood-brain barrier. AB - Efflux of choline from the rat cerebral cortex in vivo was investigated using the cup technique. After removal of the dura mater, the cup was placed on the cortex. Transmission and scanning electron microscopy revealed that the cortex was separated from the cup solution (100-300 microliter) by basal lamina, pia mater, arachnoid (with discrete defects) and remainders of the subdural neurothelium. Two kinds of experiments were carried out to determine: efflux of unlabelled choline into the cup solution; and translocation of radioactivity from the plasma into the cup solution (via blood-brain barrier and leptomeningeal layers) during i.v. infusion of [3H]choline or [14C]inulin. The former process was highly temperature-sensitive in contrast to the latter. Penicillin-G-sodium, which is known to damage the blood-brain barrier, was added to the cup solution, enhanced efflux of unlabelled choline, and caused a 5-fold increase in the rates of translocation of radioactivity during infusion of either labelled choline or inulin. In contrast, physostigmine (3 X 10(-4) M, added to cup solution) failed to enhance 3H-translocation, but markedly facilitated the efflux of unlabelled choline; this effect was highly temperature-sensitive and was blocked by atropine. It is concluded that activation of muscarinic receptors enhanced the choline efflux from cortical tissue. This effect was caused by cellular mobilization of choline presumably through an action on the metabolism of phosphatidylcholine. The effect was not due to alterations in the translocation of choline from the plasma to the cup solution, i.e. through permeability changes in the blood-brain barrier and in the leptomeningeal 'barrier'.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4041891 TI - Basal forebrain lesions produce a dissociation of trial-dependent and trial independent memory performance. AB - The behavioral effects of lesions in the basal forebrain (BF) of rats were evaluated using two tasks. The BF lesions included both the nucleus basalis magnocellularis (NBM) and the medial septal area (MSA). The first task was a Stone maze, which has 14 consecutive choice points and is a task of complex, trial-independent memory. BF lesions did not impair choice accuracy in this task. The second task was a win-shift spatial discrimination in a radial arm maze, which requires trial-dependent memory. BF lesions produced a significant decrease in choice accuracy in this task. These results demonstrate that BF lesions impair trial-dependent (working) memory but not trial-independent reference memory, and that task difficulty is not the sole factor determining whether BF lesions produce behavioral impairments. PMID- 4041892 TI - Cholinergic modulation of mediodorsal thalamic input into cingulate cortex. AB - Field potentials in cingulate cortex (area 24) produced by electrical stimulation of the mediodorsal thalamic nucleus were diminished by iontophoretic ejection of the cholinergic agonist, carbachol. The effect was frequency dependent: field potentials produced by 7.0 Hz stimulation were reduced by 34%. Potentials produced by 0.5 Hz stimulation were not significantly changed. This reduction was blocked by muscarinic but not nicotinic antagonists. PMID- 4041893 TI - Calmodulin-dependent adenylate cyclase in rat retina and the response to dopamine. AB - Adenylate cyclase activity from the rat neural retina was highly stimulated with Ca2+ and calmodulin. The retinal adenylate cyclase activity was also increased by dopamine, and the activation was not changed with or without Ca2+-calmodulin in fractions from the neural retina homogenate after sucrose density gradient centrifugation. The results suggest that the two regulation systems (i.e. dopamine and Ca2+-calmodulin) of adenylate cyclase in the rat retina appear to be independent. PMID- 4041894 TI - Sustained cerebral vasoconstriction during bilateral sympathetic stimulation in anesthetized rabbits. AB - Temporal aspects of bilateral sympathetic nerve stimulation on cerebral blood flow (CBF) were examined in anesthetized rabbits (n = 7). CBF ranged from 32 to 50 ml/min per 100 g. Bilateral stimulation reduced blood flow by 17-31% to cerebrum, diencephalon-mesencephalon and cerebellum, and responses were constant between 2 and 6 min of stimulation. Sustained cerebral vasoconstriction is consistent with an important role for sympathetic nerves in the regulation of CBF. PMID- 4041895 TI - The pituitary inhibitory system: its role in pain perception. AB - The present study was designed to investigate the pain relief mechanism of electrical stimulation to the pituitary and the relationship between hypothalamic and pituitary analgesic mechanism through the observation of monkey behavior and characteristics of tooth pulp-evoked potentials. The results suggest that pituitary-stimulating analgesia should be differentiated from hypothalamic stimulating effect. In view of the facts, the theory of the Pituitary Inhibitory System is proposed. PMID- 4041896 TI - Age-related dendritic growth in dentate gyrus of human brain is followed by regression in the 'oldest old'. AB - Dendritic extent in dentate gyrus granule cells of normal aging human brain was found to increase between middle age (fifties) and early old age (seventies). However, dendritic regression was found in the oldest old (nineties). This finding of dendritic regression following growth is in contrast to previous quantitative reports of continued dendritic growth in parahippocampal gyrus of aging human brain. This new result reinforces the concept of age and region specificity in changes in dendritic extent. PMID- 4041897 TI - Characterization of specific binding sites labeled by [3H]LSD in coronal sections of paraformaldehyde-fixed rat brain. AB - Specific, high-affinity binding of [3H]lysergic acid diethylamide (LSD) in coronal sections of paraformaldehyde-fixed rat brain is described. Intracardiac perfusion of paraformaldehyde selectively altered 40% of the total binding sites normally labeled by [3H]LSD in unfixed sections. Competition by unlabeled LSD and serotonin (5-HT) was not altered by the fixation procedure. Competition by spiperone, however, revealed that the fixation procedure preferentially altered sites for which spiperone has high affinity. This technique should facilitate the combination of neuroanatomical techniques such as radioautography and immunocytochemistry. PMID- 4041898 TI - Rats prefer ambient temperatures out of phase with their body temperature circadian rhythm. AB - Rats placed in thermally graded enclosures cyclically selected ambient temperatures about 195 degrees out of phase with the circadian variations of their hypothalamic temperature. This finding cannot be explained by the generally accepted assumption that body temperature circadian rhythm is due to a cyclic shift of the set-point temperature. PMID- 4041899 TI - A Golgi and morphometric study of the ectopic granule cells in the molecular layer of the rat cerebellum. AB - The morphological types of isolated ectopic granule cells (EGCs) were examined with Golgi-Rio Hortega staining in the cerebellar molecular layer of adult normal rats. The EGCs showed a significant reduction in the number of dendrites (mean 2.42 +/- 0.07) with respect to the controls (mean 3.97 +/- 0.09), and they usually exhibited poorly developed dendritic terminals. The karyometric analysis on semithin sections indicated that the average nuclear area in EGCs was significantly smaller (16.62 +/- 0.20 micron 2) than in normally positioned granule cells (21.08 +/- 0.24 micron 2). PMID- 4041900 TI - Distribution of osmosensitive cells in the preoptic and adjacent regions of cat brains. AB - The response of neurons in the preoptic and adjacent regions of the brain to intracarotid injection of hyperosmotic solutions was studied in 22 anesthetized cats. NaCl (0.5 M) caused a brisk acceleration of frequency lasting over 100 s in 120 of 207 units (58%). Glucose (2 M) and sucrose (2 M) had similar but smaller effects, and urea (2 M) was ineffective. Responding units were found in all parts of the preoptic region, the diagonal band of Broca (vertical limb), the lateral septal nucleus, nucleus accumbens and anterior hypothalamus. PMID- 4041901 TI - Synaptogenic effects of neonatal estradiol treatment in rat superior cervical ganglia. AB - Neonatal rats treated with testosterone propionate or 17-beta-estradiol during the first two postnatal weeks have more neurons and synapses in their superior cervical ganglia (SCGs) at 15 days of age than do vehicle-treated littermates. To determine whether a non-aromatizable androgen would similarly increase the number of SCG synapses, dihydrotestosterone (DHT) was injected into male rats beginning on the day of birth. The animals were sacrificed on postnatal day 15 and the SCGs removed on postnatal day 15. Counts of synapses showed no difference in the number of synapses between control and DHT-treated animals. These results suggest that the actions of testosterone to increase the numbers of SCG synapses may be via aromatization to estradiol. An additional study was done to determine whether the additional synapses formed in SCGs of animals treated with estradiol arise from neurons whose axons are in the cervical sympathetic trunk or from intrinsic neurons, i.e., SIF cells or other principal ganglion neurons. Neonatal males were injected with 17-beta-estradiol or vehicle beginning on the day of birth and continuing until the time of sacrifice on day 15. The number of intrinsic synapses formed under control and estradiol treatments was determined in SCGs of animals whose extrinsic synapses were caused to degenerate by severing the cervical sympathetic trunk bilaterally on postnatal day 13, two days before sacrifice. The total number of synapses (extrinsic plus intrinsic) in the ganglion after vehicle or estradiol treatment was determined in unoperated animals and used to calculate the number of extrinsic synapses.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4041902 TI - Primary cultures from defined brain areas; effects of seeding time on cell growth, astroglial content and protein synthesis. AB - The influence of seeding time on cell growth, astroglial content and on protein synthesis during cultivation was determined in primary cultures from 3 phylogenetically different brain areas from rat cerebral cortex, striatum and brainstem. Brainstem cultivated from 17-day-old embryos and all the cultures studied from the 3 brain areas of newborn and 7-day-old rat showed a similar increase in total and water-soluble protein during cultivation. Glial fibrillary acidic protein (GFAp, alpha-albumin) levels increased with age in all cultures studied. There was a rapid increase in GFAp (alpha-albumin) between 1 and 2 weeks in cultures from newborn and between 2 and 3 weeks in brainstem cultures from 17 day-old embryos, these increases being slower thereafter. Incorporation of [3H]valine into soluble protein was lower in 3-week-old cultures than in 1- and 2 week-old cultures derived from newborn and 7-day-old rat brain. The incorporation rates were similar in comparisons of the various cultures. Similar results were obtained from embryonic cultures, although the decrease in incorporation rate was between 3 and 4 weeks. The efficiency of incorporation (% TCA-precipitated material/total [3H]activity) was higher in 2- and 3-week-old than in 1-week-old cultures from newborn and 7-day-old rats and in 3- and 4-week-old cultures of brainstem from 17-day-old rat embryos. These findings suggest a cell differentiation during cultivation. The results show that seeding time has a variable influence on cultures from the different brain areas studied concerning cell growth, astroglial content and probably differentiation during cultivation. Embryonic cell cultures seem, in general, to develop one week later than neonatal and postnatal ones. Cultures of newborn rat cells from cerebral cortex, striatum and brainstem show many similarities in the above parameters during cultivation. This is also the case for brainstem cultures from embryonic rat. PMID- 4041903 TI - Gangliosides in postmitotic retina of chick embryo: changes in vivo and in cell cultures. AB - Developmental changes in ganglioside composition of postmitotic neural retina of chick embryo were analyzed by thin-layer chromatography. Gangliosides were identified by comparing their chromatographic mobilities with reference standards. The outstanding changes are decrease in the concentration of GD3L and increase in GD1a and GM1 concentrations. By depleting Muller glia cells from retina tissue of 13- and 16-day embryos (R13, R16) we determined that the bulk of the major gangliosides is associated with the neurons. Analysis of gangliosides in monolayer cultures of R13 and R16 cells highly enriched for Muller cell derived gliocytes indicated that these cells express the same types of gangliosides as neurons, but in somewhat different concentrations and relative proportions; however, after time in culture these cells showed ganglioside types and changes in ganglioside profile that are not characteristic of normal retina. The latter observation is consistent with other evidence that the phenotype of Muller glia cells becomes altered in monolayer culture. In contrast to cultures of early embryonic retina, in organ cultures of later postmitotic retina, ganglioside composition did not continue to change as in normal development. This suggests that in postmitotic retina, normal developmental progression of ganglioside changes requires systemic and/or other conditions which are missing or altered when this tissue is isolated and cultured in vitro. PMID- 4041904 TI - Transient patterns of acetylcholinesterase activity in visual cortex of the rat: normal development and the effects of neonatal monocular enucleation. AB - This paper describes the normal development and disappearance of acetylcholinesterase (AChE) activity in layer IV of rat visual cortex and the effects of neonatal monocular enucleation on this transient pattern of AChE activity. Subjects were laboratory-born male or female Long-Evans rats. Some animals underwent monocular enucleation within 6 h of birth. Animals were sacrificed at various ages and AChE activity was detected histochemically in tissue sections. AChE activity is first detectable histochemically in visual cortex area 17 as a fine fiber-like plexus in layer IV at about 7 postnatal days of age. The intensity of the staining increases during the second postnatal week and reaches peak intensity at days 12-14. The intensity of the AChE staining in layer IV of area 17 appears to decrease during the third postnatal week and the dense AChE band disappears by postnatal day 21. The distribution of AChE in layer IV of area 17 corresponds closely to the field of termination of geniculocortical projections and the fiber-like pattern of AChE activity resembles the appearance of an axonal terminal field. Neonatal monocular enucleation results in a marked decrement in the spatial extent of the AChE activity in layer IV of cortical area 17. The AChE-positive plexus is lost in the medial regions of area 17 contralateral to the enucleated eye. AChE activity remains in the lateral part of area 17, probably corresponding to that part of area 17 innervated by secondary projections from the intact ipsilateral eye. The functional role of this transient AChE activity is unknown. The present data suggest that AChE activity is characteristic of geniculocortical axon terminals during the period of time in which they are establishing functional connections with postsynaptic sites in cortex. PMID- 4041906 TI - Changes in nuclear envelope invaginations in axotomized immature and mature hamster facial motoneurons. AB - In this study, changes in the amount of nuclear envelope invaginations (NEI) were quantitatively assessed after axotomy during the late nuclear maturation stages (15, 20 and 25 days postnatal age) and in the adult (100-day-old) hamster facial motoneurons. These changes were expressed as boundary density or BA (length of nuclear envelope per unit area of nucleus). Absolute nuclear areas and perimeters were also estimated after axotomy at these ages. At 1/2 and 1 day after axotomy, no differences in the above parameters were noted at any of the operative ages. At 4 days postoperative, the peak of chromatolysis for all these ages, axotomy resulted in significant decreases in BA and nuclear perimeter in the immature neurons and no changes in BA and nuclear perimeter in the adult neurons. In addition, 4 days after axotomy at 20 days postnatal and later ages, pronounced increases in nuclear area occurred. These quantitative results are interpreted as evidence that the accelerated loss of NEI after axotomy during the final stages of nuclear maturation in these neurons is related to the formation of rough endoplasmic reticulum (RER) or Nissl substance. The hypothesis that an 'excess' of RER is accumulated during the late maturation stages and may account for the lack of NEI in the adult axotomized facial motoneuron is presented. PMID- 4041905 TI - Cell proliferation during postnatal development of the retina in the mouse. AB - Cell proliferation was studied in the developing mouse retina by autoradiography following injection of [3H]thymidine. In 1-day-old mice, the duration of the phases of the cell-division cycle was investigated in ventricular cells, the mitotically active precursors of postmitotic cells that comprise the neural retina. In the center of the retina, the generation time (T) was 30 h, consisting of 8.5 h G1 phase, 16.0 h S phase, 2.6 h (minimum) G2 phase, and 2.5 h mitosis. In the periphery, T was 28.5 h; G1, 7.5 h; S, 16.0 h; minimum G2, 2.6 h; and mitosis, 2 h. As embryogenesis proceeds, the mitotic cycle decelerates. In contrast with postembryonic cell populations (in which G2, S and M tend to be invariable), all phases of the cycle increase in duration, and most become longer than is commonly observed in mature animals. Approx. 18 generations of ventricular cells are produced. However, throughout the stage of multiplication, some cells cease dividing and differentiate. In 1-day-old mice, 23% of ventricular cells in the center of the retina and 37% in the periphery remain mitotically active. DNA synthesis ceases on the 6th day in the center and the 11th day in the periphery. PMID- 4041907 TI - Catecholaminergic fiber sprouting in granuloprival coeruleo-cerebellar cultures. AB - Neonatal mouse coeruleo-cerebellar explants exposed to cytosine arabinoside to destroy granule cell precursors demonstrated sprouting of catecholaminergic fibers after 15 days in vitro. Levels of dopamine in granuloprival coeruleo cerebellar cultures were more than twice those of control cultures. As granuloprival cerebellar cultures also demonstrate Purkinje cell axon collateral sprouting, the granuloprival coeruleo-cerebellar system, in which there is sprouting of two different neuronal groups, may provide a model to investigate the nature and specificity of the signal or signals that induce axonal sprouting. PMID- 4041908 TI - Growth cones isolated from developing rat forebrain: uptake and release of GABA and noradrenaline. AB - A growth cone-enriched fraction isolated from neonatal rat forebrain was shown to accumulate gamma-amino [3H]butyric acid ([3H]-GABA) and [3H]noradrenaline ([3H]NA). Uptake of both neurotransmitters was sodium- and temperature-dependent and exhibited saturation kinetics with Km values of 17.7 microM and 4.5 microM respectively and Vmax values of 114 pmol/min/mg protein and 59 pmol/min/mg protein respectively. Electron microscopic autoradiography showed that about 50% of isolated growth cones can accumulate [3H]GABA. Inhibitor studies showed that beta-alanine was a relatively weak inhibitor of [3H]GABA uptake compared to nipecotic acid and diamino-butyric acid. Growth cone fractions preloaded with [3H]GABA and [3H]NA demonstrated a K+ (25 mM) -induced release of both neurotransmitters. Of the K+-stimulated release of [3H]GABA 50% was Ca2+ dependent, whereas the release of [3H]NA was entirely Ca2+-independent. PMID- 4041910 TI - Survival of the ganglion cell population in the rabbit retina following neonatal visual cortex ablation. AB - Unilateral visual cortex ablations in neonatal rabbits produced no detectable loss of ganglion cells in the contralateral retina following a survival period of 3, 4 or 8 months. Analysis of neuron size distributions and neuron densities from whole-mounted retinas indicate that transneuronal retrograde degeneration does not occur in the rabbit following neonatal visual cortex removal. The results support the hypothesis that axon collaterals play a role in retinal ganglion cell survival in neonatally operated animals. The paradoxical relationship between functional sparing and ganglion cell survival is discussed. PMID- 4041909 TI - Effect of intrauterine growth retardation on developmental changes in DNA and [14C]thymidine metabolism in different regions of rat brain: histological and biochemical correlations. AB - Intrauterine growth retardation was induced in the rat by clamping the uterine artery on day 17 of gestation. The effect of hypotrophy on DNA synthesis was studied in two different cerebral structures: hippocampus and cerebellum. Accumulation of DNA in these structures was biochemically measured in parallel to the incorporation of methyl-[14C]thymidine into nucleic acid at different ages and correlated with autoradiography. The various metabolites of thymidine in acid soluble fraction were determined by using chromatographic procedures. Phosphorylation defects or reduced utilization of thymidine were found in hypotrophic rats and may delay the DNA synthesis. An essay of catch-up occurred with a different timing according to the cerebral region studied. A morphological and DNA synthesis. An essay of catch-up occurred with a different timing according to the cerebral region studied. A morphological and autoradiographic study after incorporation of [3H]thymidine was carried out in parallel. The neuronal and glial components of cytogenesis were analyzed separately and a good correlation was observed between histological and biochemical data in both groups of animals. PMID- 4041911 TI - Methylmercury poisoning of the developing nervous system in the rat: decreased activity of glutamic acid decarboxylase in cerebral cortex and neostriatum. AB - The specific activities of glutamic acid decarboxylase (GAD) and choline acetyltransferase (ChAT) were measured in 6 regions of the central nervous system in young rats, following chronic postnatal administration of methylmercuric chloride. These rats exhibited signs of neurological impairment which included visual deficits, ataxia, spasticity and myoclonus. At the onset of neurological impairment, there was a significant reduction in GAD activity in the occipital cortex (43%), frontal cortex (37%) and caudate-putamen (42%). Preceding the onset of neurological impairment, diminished GAD activity was detected only in the occipital cortex. In the cerebellum, thalamus and spinal cord, GAD activities were normal throughout the experiment. No significant differences in ChAT activity were detected in any of the 6 regions. These results are consistent with a preferential involvement of GABAergic neurons in methylmercury-induced lesions of the cerebral cortex and neostriatum. PMID- 4041912 TI - Unilateral odor deprivation: effects on the development of olfactory bulb catecholamines and behavior. AB - The present studies began an examination of the process by which unilateral odor deprivation results in a 25% reduction in the size of the olfactory bulb. Rat pups had a single naris occluded on the day after the day of birth (Day 1) and were tested at several early postnatal ages. Dopamine (DA) levels were measured to gauge the effects of deprivation on a transmitter system which is intrinsic to the bulb, while norepinephrine (NE) concentrations were assessed to determine how deprivation affects inputs to the bulb from higher brain regions. A significant reduction in DA concentration (pg/mg protein) was observed on Day 8 and persisted until Day 30 although protein concentrations (pg/mg bulb) were not affected. In contrast, deprivation did not significantly alter NE concentration. Deprived and control pups did not differ on a series of behavioral and morphometric measures, suggesting that the surgical procedure did not seriously impair normal growth patterns. The results indicate that unilateral naris occlusion induces rapid and specific changes within the olfactory bulb. PMID- 4041913 TI - Early phenobarbital-induced alterations in hippocampal acetylcholinesterase activity and behavior. AB - Early exposure to phenobarbital (PhB) causes marked destruction of large neurons which are then forming both in the hippocampus and in the cerebellum. Such exposure to PhB also reduces the achievements of mice in hippocampus-related behaviors such as radial 8-arm maze performance. Experimental evidence suggests that these behaviors are partially mediated by cholinergic transmission. We studied the performance of mice, exposed to PhB prenatally or neonatally, in radial 8-arm maze. Both treatments caused significant impairments in the animals' performance in the maze. Acetylcholinesterase (AChE) and pseudocholinesterase (pChE) activities were studied in the hippocampus and cerebellum of mice who were exposed to PhB prenatally or neonatally. These enzymes are involved both in cholinergic transmission and in neuronal development. A significant decrease (13 16%, P less than 0.01) in hippocampal AChE specific activity was found between days 15 and 22 in animals exposed to PhB neonatally. The total hippocampal activity of AChE was also greatly reduced (25-39%, P less than 0.01) during that period as a result of both the reduction in specific activity and a reduction in hippocampal weight of the treated animals. These alterations were transient and were not detected in adulthood. No changes in hippocampal AChE or pChE activities were found in animals treated prenatally. Cerebellar AChE and pChE activities were not altered after prenatal nor after neonatal exposure to PhB. It is possible that the short-term effect of neonatal treatment on AChE specific activity might mediate the long-term impairments in hippocampus-related behaviors. PMID- 4041914 TI - The role of the principal sensory nucleus in central trigeminal pattern formation. AB - Complete lesions of the principal sensory nucleus in the neonatal rat disrupts vibrissae-related pattern formation in the ventral posterior nucleus of the dorsal thalamus. Similar lesions of the spinal trigeminal nucleus do not effect pattern formation in the ventral posterior nucleus. The results are interpreted as suggesting that the principal sensory nucleus provides a template for pattern formation in central trigeminal structures. PMID- 4041915 TI - Behavioral effects of D-amphetamine in developing cats. AB - The development of the behavioral effects of amphetamine was assessed in kittens of 1-53 days of age. Amphetamine-induced increases in locomotion occurred when animals were beyond 35 days of age. Stereotypic behavior was induced at all ages tested but the predominant type of stereotypy was age-related. From 1 to 14 days amphetamine induced licking. Pendular head movements occurred when animals were under 35 days. At 14 days of age darting, a response consisting of rapid pacing and turning began to occur. Tracking, a series of horizontal and vertical head movements also began to occur after 14 days. The adult response of vertical and horizontal head movements became most prominent after 35 days. PMID- 4041916 TI - Postnatal neurogenesis in the rat hypothalamus. AB - Neurogenesis of the rat hypothalamus was studied with the [3H]thymidine autoradiography method during the first postnatal month. In the parvicellular hypothalamic nuclei a low rate (1%) of neurogenesis could be observed during the first postnatal week, but not later. There was no sign of neuron formation in the magnocellular cell groups. A number of glial cells were labeled throughout the first month in all hypothalamic nuclei at a decreasing rate. Therefore, birth is not a sharp dividing line in the neurogenesis of the hypothalamus in the rat. PMID- 4041917 TI - Transplantation of fetal postmitotic neurons to rat cortex: survival, early pathway choices and long-term projections of outgrowing axons. AB - A system for studying growth and development of transplanted subpopulations of postmitotic cerebral cortical neurons is described. The cytotoxic drug methylazoxymethanol (MAM) was given to pregnant rats on the fourteenth day of gestation to destroy precursor cells of layers II-IV of the fetal cerebral cortex. Layer V and VI precursor cells which had completed their final division before MAM treatment and were unaffected by it, were labeled by a prior injection of [3H]thymidine. This strategy provides a donor cerebral cortex containing mainly neurons destined to form layers V and VI of the adult cerebral cortex; these cells are postmitotic. Pieces of donor cerebral cortex were transplanted to the cerebral hemispheres of normal newborn hosts at one day, two days, or 6 days after MAM treatment; survival was assessed 1-12 weeks after transplantation by autoradiography of histological sections. Radiolabeled graft cells survived in 89% of recipients and many of these grew axons into the host, as indicated by retrograde labeling with horseradish peroxidase. Significant numbers of graft cells could also be stained immunocytochemically for glutamic acid decarboxylase or for the peptides, somatostatin, vasoactive intestinal polypeptide or cholecystokinin. A second group of experiments examined the routes of early axon outgrowth from normal and postmitotic fetal grafts. When the donor cortex had been incubated in a mixture of [3H]proline and [3H]leucine for 20 min prior to transplantation, the earliest axons growing out of the graft into normal newborn hosts could be assessed by autoradiography of axoplasmic transport after survivals in the host of 7 days. Normal and postmitotic grafts taken at E15 or E20 were capable of outgrowth, though the axons of E20 postmitotic cells did not grow far. The location of the transplant was the major determinant of where graft cells' axons grew and growth was mainly into existing axonal pathways of the host. In a third group of experiments, long term axonal projections from normal and postmitotic fetal transplants to 4 regions of the host brain--thalamus, contralateral cortex, striatum, and hippocampus--were examined with retrograde tracers 2-4 months after transplantation. Projections from grafts to the 4 host sites were highly dependent on the presence of nearby host axons connecting with those sites. Neurons in all types of graft projected to one or other of the 4 sites, but generally in small numbers. Higher proportions of cells in grafts from E15 MAM-treated donors projected to the host thalamus.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 4041918 TI - Early postnatal development of EEG and sleep-waking cycle in two inbred mouse strains. AB - The postnatal maturation of brain electrical activity and sleep-waking cycle were studied in two inbred mouse strains (C57BL and BALBc), previously differentiated in their sleep patterns at adult age. Genetic differences are evident during the first postnatal period (until day 12) in the maturation of electrical activity which is both earlier and slower in C57BL than in BALBc. On the other hand, from day 12 onwards, as soon as the sleep-waking cycle can be defined by using EEG morphology to select quiet sleep (QS) and active sleep (AS) C57BL is characterized by a higher amount of AS and a lower amount of waking (W) than BALBc, as found in juvenile and adult mice. These differences appear a little later when the recordings are performed on animals which are isolated instead of being left with the rest of the litter. PMID- 4041919 TI - The morphology and phased outgrowth of callosal axons in the fetal rat. AB - The growth of axons of the corpus callosum was studied in fetal and early postnatal rats by means of anterograde and retrograde transport of horseradish peroxidase (HRP) applied to the developing cerebral cortex in the frontal and presumptive sensory motor regions. In the sensorimotor regions, the first axons to reach the midline at E18 arise from two separated groups of cells situated medially near the superior sagittal sinus and laterally just above the rhinal sulcus. Each group forms a stratum just beneath the cortical plate. Axons from cells in intervening regions arrive at the midline approximately one day later. By the first postnatal day (P0), a second stratum of callosally projecting cells can be identified superficial to the first. Callosal axons grow out from this stratum in the same sequence as those from the deeper stratum, axons from medial and lateral regions preceding those from intervening regions. [3H]thymidine labeling of animals later injected with HRP, indicates that callosal cells in the deep stratum enter their final mitosis at E15 and those in the superficial stratum at E16. Growing callosal axons have identifiable growth cones and filopodia at their tips but, as far as they could be traced, the axons do not branch. They grow orthogonal to radial glial processes of the cerebral hemisphere and diverge early from simultaneously outgrowing corticofugal axons directed to subcortical sites, as though following separate cues. Callosal axons advancing from one side grow directly into the path taken by those advancing from the other side. PMID- 4041920 TI - Ontogenesis of proenkephalin products in rat striatum and the inhibitory effects of low-level lead exposure. AB - Certain developmental abnormalities have been associated with environmental exposure to lead and our previous studies have indicated that the endogenous opioid system is disrupted by this metal. In connection with this we report the ontogeny of proenkephalin products in the rat striatum determined by combined HPLC and bioassay and the effects of low-level lead exposure on this ontogeny. The development of Met-enkephalin levels was dissimilar from that of the other proenkephalin products, Met-enkephalyl-Arg6-Phe7, Met-enkephalyl-Arg6-Gly7-Leu8 and Leu-enkephalin. The ratios of Met-enkephalin containing peptides to Leu enkephalin was less than the 6:1 ratio predicted from the proenkephalin structure. Lead (administered in the maternal drinking water, from conception to weaning at 100, 300 and 1000 ppm) caused a dose-related depression of the levels of proenkephalin products in rat striatum at 10, 21 and 30 days after birth. The most pronounced effects were observed at 10 days and the most persistent effects were seen with Met-enkephalin. Peak blood lead levels were below 45 micrograms/100 ml in the 100 and 300 ppm lead-dosed groups and in all lead-dosed groups at 10 days after birth. It is suggested that lead may have inhibitory effects on proenkephalin-processing enzymes. PMID- 4041921 TI - Synapse elimination in the developing visual cortex: a morphometric analysis in normal and dark-reared cats. AB - The elimination of synapses from developing visual cortex, occurring after day 70 in cat, is thought to result from competition among redundant axons innervating area 17. The dependence of this elimination on visual experience was tested by comparing normal cats at 70 and 220 days of age with littermates dark-reared from day 70 to day 220. Thickness of all cortical laminae, numerical density (NV) of neurons in layers I-III and NV of synapses in layers I-III were measured in two regions of area 17, corresponding to central (0-5 degrees) and peripheral (15-20 degrees) representations of the binocular visual field. In the central region, normal development was characterized by a 25% decrease in thickness of layers I III with a corresponding increase in the NV of neurons. The NV of synapses in layer I decreased by 29%, with a 52% decrease in the number of synapses under one mm2 of pial surface. In layers II-III the NV of synapses decreased by 31%, with a 46% decrease in the number of synapses under 1 mm2 of pial surface. These developmental changes were unaffected by dark-rearing. In the peripheral region, normal cats exhibited no significant changes in laminar thickness or in NV of synapses, although the number of synapses under 1 mm2 of pial surface decreased by 25% in layer I and by 18% in layers II-III. In dark-reared cats the thickness of layers I-III decreased by 26% with a corresponding increase in the NV of neurons. The NV of synapses in layer I decreased by 18% and the number of synapses under 1 mm2 of pial surface by 51%. In layers II-III the NV of synapses decreased by 22% and the number of synapses under 1 mm2 of pial surface by 39%. Thus, in normal development the loss of synapses is greater from central than from peripheral representations of area 17. Dark-rearing does not alter the elimination of synapses in central cortex, but accelerates this loss in peripheral cortex. PMID- 4041922 TI - Tenotomy decreases sympathetic neuronal survival factors in avian smooth muscle. AB - The expansor secundariorum of the chicken wing has a high concentration of survival factor activity for sympathetic neurons. The effect of tenotomy on this activity has been examined in newly hatched and older birds. Survival factor activity was assayed with dissociated embryonic neurons and found to be decreased after tenotomy to low levels in the newly hatched but not the older birds. No change in dopamine beta-hydroxylase concentration was detected, suggesting that tenotomy does not significantly alter impulse activity in the sympathetic innervation. The results are compared with findings after tenotomy in skeletal muscles and contrasted with increased survival factor activity produced by denervation of the expansor secundariorum. PMID- 4041923 TI - The corticomotoneuronal component of the pyramidal tract: corticomotoneuronal connections and functions in primates. AB - Corticomotoneuronal fibers make up a functional component of the pyramidal tract corticospinal system which is characteristic of primates. The corticomotoneuronal fibers include large, rapidly conducting axons. They arise from somatotopically arranged areas of precentral cortex and the largest concentration of pyramidal cells of origin in the deep part of lamina V is in area 4. Their influence is exerted contralaterally on the spinal cord, where monosynaptic excitation of spinal motoneurons occurs. Motoneurons innervating distally acting muscles are preferentially excited and marked convergence of corticomotoneuronal influences occurs on these. The excitatory post-synaptic potentials in these motoneurons are characterized by the property of temporal facilitation. Intraspinal divergence of the terminal arborizations of individual corticomotoneuronal fibers could permit the engagement of large populations of motoneurons and also the activation of excitatory and inhibitory interneurons and propriospinal neurons for that region of the spinal cord. Corticomotoneuronal synapses may be located more distally on the dendrites of motoneurons than are the monosynaptic connections from group Ia afferents. The corticomotoneuronal excitation has been demonstrated to be effective in natural functional states when the conscious animal is performing learned movement tasks. Abolition of corticomotoneuronal influences causes a permanent deficit in the fractionation of use of distal muscles and an inability to carry out independent movements of the fingers. PMID- 4041924 TI - Neonatal monosodium glutamate administration alters noradrenergic measures in the brainstem of the mouse. AB - Mice treated neonatally with MSG (4 mg/g) were compared to saline-injected controls on a number of neurochemical parameters of brainstem noradrenergic activity. MSG treatment resulted in an attenuation of brainstem norepinephrine (NE) decline after alpha-methyl-p-tyrosine administration. Neonatal MSG administration did not result in alterations in the steady state levels of brainstem NE or MOPEG. The synthesis of NE was slightly increased in the pons medulla of MSG-treated mice as indexed by pargyline-induced NE accumulation. NE release, however, appeared diminished as reflected by a significant (p less than 0.05) decrease in the ratio of normetanephrine to NE found in the pons-medulla of MSG-treated mice given pargyline. The results suggest that MSG-induced damage to the arcuate nucleus produces selective alterations in brainstem NE systems. These alterations may reflect the toxic action of MSG on the opiomelanocortin neurons of the arcuate nucleus or other descending systems that are damaged by MSG. The loss of the descending opiomelanocortin input to the brainstem could result in these types of neurochemical consequences since the pharmacologic action of opiate drugs results in a selective enhancement of brainstem NE turnover in rodents. PMID- 4041925 TI - Distribution of retinoids in different compartments of the posterior segment of the rabbit eye. AB - Using high-performance liquid chromatography, the amounts of all-trans retinol, retinal and retinyl palmitate were measured in the following ocular tissues and fluid of the light (LA) and dark adapted (DA) rabbit: cytosol and membrane fractions of the retina (R/C and R/M), cytosol and membrane fractions of the retinal pigment epithelium (RPE/C and RPE/M), subretinal fluid collected from the inter-photoreceptor matrix (S/R) and the matrix between apical microvilli of the RPE (S/RPE). The total amount of all-trans retinol extracted from LA eyes, 2.74 nmol per eye, was ten times greater than the amount extracted from DA eyes. In the LA eye, most of the all-trans retinol was extracted from the membrane fraction of the retina (67%); in the DA eye, most of the retinol was extracted from the cytosol fraction of the retina (58%). In contrast, the DA eye yielded more all-trans retinal (9.84 nmol) than the LA eye (5.80 nmol) and most of this retinoid was recovered from the cytosol and membrane fractions of the retina. A higher amount of all-trans retinyl palmitate was recovered from the LA eye (5.88 nmol) than the DA eye (2.02 nmol). Although most of this retinyl palmitate was extracted from the cytosol fraction of the RPE (45%, LA eye), appreciable amounts were found in all other ocular compartments. The amount of retinyl palmitate in the LA eye exceeded that of the DA eye in every compartment examined in the present study, suggesting a possible important role of retinyl esters in the visual cycle. PMID- 4041926 TI - Hypothalamic circuits involved in the regulation of seasonal and circadian rhythms in male golden hamsters. AB - Hypothalamic knife cuts were employed to investigate the pathways which mediate the gonadal regression induced by short-day photoperiods in male golden hamsters (Mesocricetus auratus). Bilateral horizontal cuts placed between the suprachiasmatic nucleus and the paraventricular nucleus (PVN), as well as cuts placed through the PVN, prevented testicular regression in animals kept on a photoperiod that provided only 6 hr of light/day. Identical effects were obtained when the cuts were placed just dorsal to the PVN. Unilateral damage or sham surgery failed to block gonadal regression. The entrainment of circadian rhythms of locomotor activity to the light-dark cycle was not affected by cuts that abolished the effects of photoperiod on testicular regression. The results are discussed in the context of current models of neural control of the pineal gland and melatonin production. PMID- 4041927 TI - Visual circadian rhythmicity in splitbrain crayfish: a plastic behavioral expression of symmetric circadian pacemakers. AB - Electroretinographic evoked potentials (ERG's) were continuously recorded in dark adapted, splitbrain crayfishes Procambarus bouvieri. Pulses of light (0.95 cd/m2) illuminating the left or the right eyes were alternatively applied every 15 or 30 min. As compared to intact crayfish, uni or bilateral damping or suppression of circadian retinal sensitivity rhythm could be caused by surgical bisection of cerebral ganglion in these crustaceans. The damped ERG circadian rhythm was rapidly reversed by reduction or elimination of the test light stimulus to the contralateral eye. Given the redundant processing of pacemaking information coming from bilaterally positioned cephalic circadian pacemakers to the central nervous system in splitbrain crayfish, photodependent damping of ERG rhythm revealed a plastic potential of central circadian pacemakers. The possibility that a strong but reversible inhibitory influence acts simultaneously upon the left and right protocerebral circadian pacemakers while receiving bilateral photic stimulation is considered. PMID- 4041928 TI - Monoamine transmitter release induced by tetrahydro-beta-carboline perfused in hippocampus of the unrestrained rat. AB - Guide cannulae for unilateral push-pull perfusion were implanted stereotaxically to rest just dorsal to the hippocampus of the rat. On recovery, a tissue site in the hippocampus was double-labelled with a 1.0 microliter volume of [14C]-5 hydroxytryptamine (5-HT) and [3H]-norepinephrine (NE). Then the site was perfused by means of push-pull cannulae at a rate of 25 microliters/min with an osmotically-balanced CSF. When tetrahydro-beta-carboline (THBC) was added to the CSF perfusate in a concentration of 0.5-5.0 micrograms/125 microliters, the pattern of efflux of both of the monoamines exhibited an increase in release which was either immediate or delayed depending on the concentration and site of the hippocampal perfusion. Further, if the interval of a sequence of repeated perfusions was less than one day, the efflux of either [3H]-NE or [14C]-5-HT was attenuated. The addition of chlordiazepoxide to the CSF perfusate in a dose of 1.6 microgram/1.0 microliter did not affect the resting efflux of either of the monoamines, but did tend to reduce the THBC-induced release. A morphological "mapping" showed that the anatomical sites of perfusion in the hippocampus were homologous to those within which THBC injected locally induces anxiety-like behavior in the rat. Thus, it is envisaged that this beta-carboline serves to alter the behavior of the animal by a differential shift in the synaptic activity of monoamines within neurons of this limbic system structure which is implicated in emotional responses. PMID- 4041929 TI - Simultaneous recording of substantia nigra neurons and voltammetric release of dopamine in the caudate of behaving cats. AB - Simultaneous electrophysiological recordings of single dopamine-containing neurons in the pars compacta of the substantia nigra and the voltammetric release of dopamine in the caudate were made in the behaving cat. Unit activity showed no significant changes during sleep and small changes during active waking, while the release of dopamine in post-synaptic target regions of the caudate nucleus decreased by approximately 35% during sleep and increased approximately 50% during movement. These data demonstrate that recording the electrophysiological activity of single dopamine-containing neurons alone does not accurately reflect the functional state of the central dopamine system. The present study is the first report on the simultaneous measurement of the post-synaptic release of a neurotransmitter and the electrophysiological recording of neurons identified to contain that transmitter substance. PMID- 4041930 TI - Suppression of self-stimulation of the medial prefrontal cortex after local micro injection of kainic acid in the rat. AB - The question of whether neurons versus fibers of passage in the medial prefrontal cortex (MPC) are essential in maintaining self-stimulation of this same area of the brain was examined. Rats were prepared with electrode-guide cannulae implanted stereotaxically to rest within MPC. A micro-injection of (KA), 10 nmol/1.0 microliter, into the right MPC produced a clear degeneration of neuronal cell bodies characterized by picnocytosis and glial invasion of the tissue surrounding the tip of the electrode. These histopathological changes were correlated with a permanent abolition of self-stimulation of the right MPC. In contrast, self-stimulation of the contralateral side of the MPC, micro-injected with 0.9% NaCl vehicle as a control, was unaffected. These results suggest that neurons of the MPC are part of the neural substrate underlying self-stimulation behavior in this cortical area of the rat. PMID- 4041931 TI - [The effect of substance DH 1011 on vascular smooth muscle]. PMID- 4041932 TI - [Use of apatite ceramic in stomatological implants]. PMID- 4041933 TI - [Humidification and warming of respiratory gases in high-frequency jet pulmonary ventilation]. PMID- 4041934 TI - [The effect of l-propoxyphene on experimental cough]. PMID- 4041935 TI - [The importance of one-time aorto-arteriography in vascular surgery]. PMID- 4041936 TI - [Appendicitis in children]. PMID- 4041937 TI - [The importance of radiotherapy in enthesis pathology of the elbow joint]. PMID- 4041938 TI - [Malignant lymphoma of the stomach]. PMID- 4041939 TI - [A syndrome similar to systemic lupus erythematosus caused by penicillamine in patients with Wilson's disease]. PMID- 4041940 TI - Identification and antibiotic susceptibility of bacterial isolates from burned patients. AB - We retrieved bacterial blood isolates from 397 adult burned patients admitted over a 7-year period. Sixty-two patients (15.6 per cent) developed true-positive bacterial blood cultures (judged non-contaminants), and of these 30 (48.4 per cent) expired. Pseudomonas aeruginosa (24 isolates), Staphylococcus aureus (19) and Klebsiella pneumoniae (19) were the most frequent isolates. In vitro susceptibilities of 149 isolates were determined to 12 antibiotics (gentamicin, amikacin, ticarcillin, piperacillin, mezlocillin, azlocillin, cefazolin, cefotaxime, ceftazidime, cefoperazone, thienamycin and ticarcillin-clavulinic acid) using agar diffusion assay. Thienamycin proved the most active agent (97 per cent of isolates susceptible). Cefoperazone was the most active cephalosporin (95 per cent susceptible). Twenty-eight organisms demonstrated multiple drug resistance; patients with such organisms had a 71 per cent mortality. Thienamycin was the most active agent against such isolates (27/28 susceptible). Susceptibilities of all 149 isolates to combinations of antibiotics were calculated, assuming no synergism or antagonism; some combinations of third generation cephalosporins with the newer penicillins may prove to be as effective as combinations including aminoglycosides. PMID- 4041941 TI - Incidence of burn wound sepsis in 600 burned patients treated in a developing country. AB - Infection is the most important problem in the treatment of burns in a developing country. A burn compromises a major body protective mechanism, namely the skin. Hence, the susceptibility to local infection increases at these sites. The incidence of burn wound sepsis is very high in south India as the socio-economic conditions and the standard of personal hygiene are poor and the hot moist climatic conditions encourage bacterial growth. These three factors are rarely present in the temperate zone countries of Europe and North America. This study was undertaken to identify more clearly the factors that are responsible for the higher incidence of burn wound infection and to formulate methods of treatment which are appropriate for our patient population living in a tropical country. PMID- 4041942 TI - Histopathological and ultrastructural change in liver tissue from burned patients. AB - Histopathological studies were made on samples of liver and spleen tissue taken post mortem from 59 patients with severe burns. Samples from 8 patients were also studied using the transmission electron microscope. The main pathological findings were degeneration and necrosis of hepatic cells and proliferation of Kupffer cells showing active phagocytosis. Their causes in relation to the time of death after burning and severity of injury have been discussed. The proliferation of Kupffer cells may be a compensatory reaction to the severe splenic injury seen in the patients. PMID- 4041943 TI - Role of escharotomy and fasciotomy as a first aid measure in the early treatment of an electrically burned arm and wrist. AB - The saving of the hand and forearm of a patient with a deep circumferential electrical burn of the wrist and forearm following contact with 10 000 V AC demonstrates the important role played by escharotomy and fasciotomy in the early treatment of electrically injured extremities. PMID- 4041944 TI - Electrical injuries due to railway high tension cables. AB - We have noted a large number of young boys being admitted to our Unit with burns due to railway high tension cables. On review of these cases we have noted: most of the burns were due to arcing, there is a high level of ignorance among the population at risk. We propose some ways of preventing these injuries. PMID- 4041945 TI - Burn injuries from portable butane camping stoves. AB - Admissions to the Wessex Regional Burns Unit for injuries sustained whilst using portable butane camping stoves are reviewed. There have been 31 cases of such injuries in the past 10 years with one fatal outcome. Most accidents occurred while changing the canister. The number of accidents occurring suggests that these stoves must be regarded as intrinsically very hazardous and that a greater awareness of the dangers by users is necessary. PMID- 4041946 TI - Intra-arterial infusions in the treatment of hydrofluoric acid burns. AB - Burns due to hydrofluoric acid are uncommon, but are severe injuries. The mode of action is discussed briefly and the routine management of these patients is outlined. The use of intra-arterial infusions of calcium gluconate is stressed, and case reports are given to support its use. PMID- 4041947 TI - Bandages of boiled potato peels. AB - The use of potato peels as a dressing for burn wounds has been reported previously. A technique of preparing bandage rolls with boiled potato peels is now presented, which makes dressing of a burn wound more convenient. PMID- 4041948 TI - Foetal monitoring during surgery unrelated to pregnancy. PMID- 4041949 TI - Spinal cord blood flow following sub-arachnoid lidocaine. AB - Twelve mongrel dogs were randomized into two equal groups. Cervical, thoracic and lumbosacral spinal cord and spinal dural blood flows were measured using the radioactive microsphere technique. Blood flow determinations were made prior to and 20 and 40 minutes following lumbar subarachnoid injection of: two per cent lidocaine (100 mg) or two per cent lidocaine (100 mg) with 1/25,000 epinephrine (200 micrograms). Dogs receiving subarachnoid lidocaine demonstrated a decrease in mean arterial blood pressure of 23 per cent and 14 per cent (p less than 0.05), while dogs receiving lidocaine with epinephrine had a decrease of 38 and 34 per cent (p less than 0.05) at 20 and 40 minutes respectively. Cardiac index was not significantly changed in either group. Lumbar subarachnoid lidocaine (100 mg) produced a rapid regional dural hyperemia (observed at 20 minutes postinjection) and a delayed regional spinal cord hyperemia (observed at 40 minutes postinjection) which were not observed following the addition of epinephrine (200 micrograms). PMID- 4041950 TI - Lack of effects of d-tubocurarine and pancuronium on the slow action potential of the guinea pig papillary muscle. AB - Inotropic effects of non-depolarizing muscle relaxants were examined with guinea pig ventricular papillary muscle depolarized to -47 mV in high K Ba-Tyrode solution. Field stimulation of 0.1 Hz elicited the slow action potential, a measure of the calcium current. The amplitude, the duration at 0 mV level and dV/dt of the action potential were monitored together with the contractile tension. Amelizol (3 mg X ml-1 d-tubocurarine (d-tc) and 5 mg X ml-1 chlorobutanol) depressed the four functions in a dose-dependent manner, while crystalline d-tc did not. Chlorobutanol (the antimicrobial preservative) had the same effects as Amelizol. Neither Mioblock (2 mg X ml-1 pancuronium and unpublished preservative) nor crystalline pancuronium altered the functions. These findings suggest that the negative inotropic effect of Amelizol is not due to d-tc but to chlorobutanol, which may exert its effect by depressing the calcium current. The lack of change in the slow action potential seen with pancuronium may indicate no direct effect on the calcium current, thereby further suggesting absent direct beta-adrenomimetic action of this agent. PMID- 4041951 TI - Refraining from cigarette smoking before premedication does not decrease the risk of acid pulmonary aspiration during anaesthesia. AB - Seventy-four habitual smokers who had refrained overnight from cigarette smoking and were undergoing elective orthopedic surgery were allocated randomly to two groups in order to investigate the effect of smoking two cigarettes before premedication on volume and pH of gastric contents. The smoking group was allowed to smoke two cigarettes while the non-smoking group was not allowed to smoke. There was no significant difference in volume or pH between the groups, either just after intubation or prior to extubation, thus indicating no decreased risk of acid pulmonary aspiration because of refraining acutely from cigarette smoking. PMID- 4041952 TI - Epidural fentanyl, with and without epinephrine for post-Caesarean section analgesia. AB - Using a double-bolus technique, the efficacy and safety of epidural fentanyl with and without epinephrine 1:400,000 for post-Caesarean section analgesia was examined in 30 patients. The addition of 25 micrograms epinephrine to the fentanyl (100 micrograms) did not potentiate the speed of onset but did significantly prolong the duration of action of the second dose. The only side effect encountered was pruritus, which was significantly increased (from 17-44 per cent) when epinephrine was added. The results indicate a clinical advantage of prolonging the duration of action of fentanyl for post-Caesarean Section analgesia with the addition of epinephrine, but the cumbersome and time-consuming nature of a double-bolus technique limits its clinical value. The relative safety of epidural fentanyl with and without epinephrine was confirmed by the absence of respiratory depression, drowsiness or hypotension in all patients. PMID- 4041953 TI - Foetal monitoring in parturients undergoing surgery unrelated to pregnancy. AB - Foetal heart rate and tocodynamic monitoring of the uterus was performed in five pregnant patients undergoing urgent or emergency surgery unrelated to their pregnancy. All received general anaesthesia with halothane or enflurane and nitrous oxide. The loss of beat-to-beat variation of the foetal heart rate was observed in all patients under general anaesthesia, and is probably normal for the anaesthetized foetus. Since continuous intraoperative monitoring of foetal heart rate in pregnant patients is technically feasible during peripheral surgery and during many intra-abdominal procedures, attempts should be made to monitor foetal heart rate in all anaesthetized parturients to assure that the anaesthetic is not causing foetal insult. Postoperative monitoring of uterine tone is useful in the diagnosis and treatment of postoperative premature labor. PMID- 4041954 TI - Spinal anaesthesia with meperidine as the sole agent. AB - Twenty male patients of ASA physical status I or II undergoing surgery of the perineal or inguinal areas received intrathecal meperidine in a dose of 1 mg X kg 1 as the sole anaesthetic agent. There was sensory and motor block within ten minutes of intrathecal injection of meperidine and surgery was performed with complete analgesia. The duration of surgery was 39.7 +/- 14 (mean +/- SD) minutes. Prolonged postoperative analgesia was obtained and some patients did not require additional narcotic analgesic during the postoperative period, lasting up to seven days. Side effects included nausea and vomiting (six patients), hypotension (five patients), pruritus (five patients) and urinary retention (two patients). There was no early or late respiratory depression. It is concluded that intrathecal meperidine in a dose of 1 mg X kg-1 is effective as the sole agent for spinal anaesthesia and produces prolonged postoperative analgesia. It offers an advantage for such painful operations as haemorrhoidectomy and anal fissurectomy where its prolonged analgesic effect is desirable. It could also serve as an alternative agent for spinal anaesthesia when a local anaesthetic is not available. PMID- 4041955 TI - Blood glucose control by an artificial endocrine pancreas in a patient with phaeochromocytoma. AB - In a patient with phaeochromocytoma who presented with unstable diabetes mellitus, an artificial endocrine pancreas was used intraoperatively. Anaesthetic agents included enflurane, nitrous oxide and oxygen. Nicardipine was used to control hypertensive episodes. The initial blood glucose concentration was 173 mg X dl-1 and it decreased to 110 mg X dl-1 in response to insulin infusion, but plasma catecholamines were markedly increased. Seventy minutes later, the glucose concentration increased progressively to 249 mg X dl-1 despite massive insulin infusion, maximally 5.64 mU X kg-1 X min-1. The blood glucose concentration reached a peak at the time of the ligation of the venous drainage from the tumour and the peak was coincident with that of plasma catecholamine levels (epinephrine: 20.8 ng X ml-1, norepinephrine 16.4 ng X ml-1). Both glucose and catecholamine concentrations decreased promptly after removal of the tumour and hypotension followed likely because of a persistent vasodilatatory effect of nicardipine. The profiles of blood glucose, insulin and glucose infusion rates provided by the artificial endocrine pancreas suggested that the insulin resistance began to be reversed shortly after removal of the phaeochromocytoma. PMID- 4041956 TI - Anaesthetic implications of nemaline rod myopathy. AB - Nemaline rod myopathy is an inherited congenital myopathy first described in 1963. Affected patients characteristically present in infancy with a non progressive hypotonia and symmetrical muscle weakness. The disease affects all skeletal muscles including the diaphragm with sparing of cardiac and other muscle. Facial dysmorphism is common as are skeletal deformities, including kyphosis, scoliosis and pectus excavatum. We present two sisters with nemaline rod myopathy and their anaesthetic management for scoliosis surgery. Facial dysmorphism was a feature of both cases. Preoperatively, both patients demonstrated poor respiratory function on pulmonary function testing. Both cases were successfully managed using controlled ventilation and inhalational anaesthetic agents, avoiding muscle relaxants. Postoperatively, there were no respiratory complications. Although one case report describes the use of succinylcholine and pancuronium in a patient with nemaline rod myopathy, we feel that neuromuscular blocking agents should be avoided where possible and only used with careful monitoring. PMID- 4041957 TI - Use of a modified Doppler flow detector for percutaneous cannulation of the internal jugular vein. AB - To lessen the risks associated with cannulation of the internal jugular vein, a method to identify the contours of the carotid artery and internal jugular vein at the site of cannulation is proposed. This method uses a doppler flow detector equipped with an adjustable electronic filter which selectively enhances the sound component due either to the arterial or venous flow. This method has been applied clinically and was found to be useful in the identification of the vessels. Since doppler flow detectors are readily available in many hospitals and the required modification is simple, we hope that other institutions will find this technique useful in their clinical practice. PMID- 4041958 TI - Availability of dantrolene in Canadian hospitals. PMID- 4041959 TI - Hyperventilation does not affect the incidence of paresthesiae and blood vessel cannulation during epidural catheter insertion. PMID- 4041960 TI - N,N'-Ethylene-bis(iodoacetamide) as a probe for structural and functional characteristics of brine shrimp, squid, and bovine tubulins. AB - We have developed a simple probe for certain functionally significant features of the tubulin molecule. When bovine brain tubulin is treated with N,N'-ethylene bis(iodoacetamide) (EBI), two intrachain cross-links, designated beta s and beta *, are formed in beta-tubulin, each one with a unique effect on the electrophoretic mobility of beta on gels containing sodium dodecyl sulfate. Formation of the beta * cross-link, which involves at least one assembly-critical sulfhydryl, is completely inhibited by colchicine and its congeners, while that of beta s is inhibited completely by maytansine and GTP and partly by vinblastine. To see how conserved this complex pattern is in evolution we examined tubulins from the brine shrimp Artemia and the squid Loligo. In both tubulins EBI forms the beta * cross-link in a reaction inhibitable by colchicine, podophyllotoxin, and nocodazole. In each tubulin, EBI appears to form a second intrachain cross-link in a reaction that can be inhibited completely by maytansine and GTP and partly by vinblastine. In Artemia, this cross-link alters the electrophoretic mobility to a slightly smaller extent than is the case for beta s in bovine brain, but in Loligo the alteration is much greater. It seems that the ligand-binding sites, the critical sulfhydryls, and their spatial interrelationships are strongly conserved and that the beta s sulfhydryls or the sequence between them are less strongly conserved in evolution. PMID- 4041961 TI - Genetic and biochemical studies with mutants of mammalian cells affected in microtubule-related proteins other than tubulin: mitochondrial localization of a microtubule-related protein. AB - In Chinese hamster ovary cells, stable mutants exhibiting specific resistance or collateral sensitivity towards the various microtubule inhibitors podophyllotoxin, colchicine, griseofulvin, taxol, nocodazole, vinblastine, and maytansine have been isolated. A number of independent mutants selected for resistance to podophyllotoxin and colchicine contain electrophoretically altered forms of two proteins, P1 and P2, of relative molecular masses of approximately 63 000 and 69 000, respectively. The proteins P1 and P2 have been shown to be microtubule related by a number of different genetic and biochemical criteria and are among the major proteins of Chinese hamster ovary cells, being present in approximately equimolar amounts with tubulin. In addition, a griseofulvin resistant mutant contains a novel mutation (presumably nonsense) which reduces the relative molecular mass of a protein, P5 (relative mass congruent to 200 000), by about 20 000. Specific antibodies to protein P1 have been raised and cross-reactivity studies show that a similar protein is also present in cells from all vertebrate species examined, viz. man, monkey, mouse, Chinese hamster, Syrian hamster, and chicken. Immunofluorescence studies with anti-P1 and anti tubulin antibodies show that, in interphase cells from various species, the P1 antibody reacts specifically with mitochondria whose overall cellular distribution is strikingly similar to the distribution of microtubules. The mitochondrial localization of the microtubule-related protein P1 provides strong suggestive evidence regarding the existence of a chemical and functional linkage between these two structures, with protein P1 playing an important role in this linkage. Some implication of these results are discussed and it is suggested that mitochondria play an important role in the dynamics of microtubules. PMID- 4041962 TI - Maytansine-resistant mutants of Chinese hamster ovary cells with an alteration in alpha-tubulin. AB - Mutant clones of Chinese hamster ovary cells resistant to killing by the Vinca alkaloid maytansine have been isolated using a single-step procedure. These mutants are threefold more resistant to killing by the drug than the wild-type parent. The majority of the clones (30 to 34) probably contain alterations in membrane permeability based on their cross-resistance to an unrelated drug, puromycin. Two of the four puromycin-sensitive clones were found to contain "extra" spots which migrated close to alpha-tubulin on two-dimensional gels. The "extra" spots were shown to be electrophoretic variants of alpha-tubulin with an identical two-dimensional tryptic peptide map to that of the wild-type alpha tubulin. The alpha-tubulin mutants were cross-resistant to other microtubule disrupting drugs such as griseofulvin, vinblastine, and colcemid, but were more sensitive to the microtubule-stabilizing agent taxol than the wild-type parental cells. Mutant--wild-type hybrids were found to be resistant to levels of maytansine intermediate between the lethal doses for mutant and wild-type cells. A possible explanation for the drug resistance of these mutants is discussed. PMID- 4041963 TI - Elongation of cytoplasmic processes during gametic mating: models for actin-based motility. AB - The acrosomal processes of Thyone and Limulus sperm and the fertilization tubule of mt+ gametes of Chlamydomonas are interesting models for actin-based motility. Each is a long thin process that elongates rapidly and contains a core of actin filaments having uniform polarity: arrowheads formed by myosin subfragments point toward the base of the processes. In Limulus, directed outgrowth of the acrosomal process is achieved by a rearrangement in the packing of superhelically coiled actin filaments that form during spermatogenesis. In contrast, outgrowth of the acrosomal process in Thyone and the fertilization tubule in Chlamydomonas is accompanied by actin polymerization. Both Thyone and Chlamydomonas possess structures, the actomere and the doublet zone, respectively, that serve as microfilament organizing centers, nucleating actin polymerization and defining the polarity of the growing filaments. Alkalinization of the cytoplasm may promote polymerization of actin in Thyone, whereas an apparent rise in the intracellular Ca2+ concentration is associated with the transmission of intracellular signals during mating in Chlamydomonas. Further examination of these three actin-based motile systems should provide new insights into the assembly of the actin cytoskeleton, a process critical for many forms of nonmuscle cellular motility. PMID- 4041964 TI - Nuclear RNA-associated proteins and their relationship to the nuclear matrix and related structures in HeLa cells. AB - The ultrastructure and the polypeptide composition of residual nuclear substructures including nuclear matrices, nuclear ghosts, and residual envelopes were investigated by means of electron microscopy and two-dimensional gel electrophoresis. Nuclear matrices were prepared by digesting isolated nuclei with DNase I alone, followed by high-salt extraction in 2 M NaCl. Nuclear ghosts were obtained by high-salt extraction of nuclei previously digested with DNase and RNase in MgCl2-containing buffers. To prepare residual envelopes, nuclei were first digested with RNase in the presence of EDTA, then digested with Mg2+ activated DNase I, and extracted in 2 M NaCl. The results of this comparative study support the conclusion that the intranuclear matrix is made of two distinct RNA-containing elements. One of these elements appears on ultrathin sections as a thin fibrillar network. It disappears from RNase-digested nuclei, together with numerous basic proteins, whatever the conditions of digestion. Although this element is present in extranucleolar territories, it is a major component of residual nucleoli. The second element appears as coarse-beaded fibers absent from the nucleolar areas. Its preservation in residual nuclear substructures depends on the presence of Mg2+ ions during RNase digestion of nuclei. It is enriched in two minor basic proteins of relative mass 49 000 and 70 000. The involvement of this fibrogranular element in heterogeneous nuclear RNA attachment to the nuclear matrix is discussed. PMID- 4041965 TI - An association between replicating adenovirus DNA and the nuclear matrix of infected HeLa cells. AB - An association between newly synthesized human adenovirus type 5 DNA and the nuclear matrix of infected HeLa cells is described. Adenovirus-infected cells were pulsed labeled with [3H]thymidine late in infection and the nuclear matrix was prepared. After a 1-min pulse more than 95% of the labeled viral DNA was matrix associated and, when compared with total cell DNA, was resistant to DNase I digestion. When the pulse is longer or is followed by a chase period, the viral DNA remains nuclear matrix associated and less nuclease sensitive than bulk cellular DNA. The resistance to nuclease digestion may result from the close association of viral DNA with the nuclear matrix or could be due to a number of viral-specific proteins which are nuclear matrix associated. It is concluded that viral DNA synthesis occurs in association with the nuclear matrix and the newly synthesized DNA remains matrix associated until it is incorporated into a mature virus particle. PMID- 4041966 TI - Studies on lectins. LIX. Isolation and properties of lectins from fruiting bodies of Xerocomus chrysenteron and Lactarius lignyotus. AB - The lectins of fruiting bodies of Xerocomus chrysenteron and Lactarius lignyotus were purified on Sepharose 4B containing immobilized fetuin. Both lectins agglutinate human erythrocytes nonspecifically at limit concentrations of 15 micrograms/mL. Their erythroagglutinating activities are not inhibited by simple sugars; desialyzed fetuin, desialyzed glycoprotein from edible bird's nest, and desialyzed mucin from porcine submaxillary glands are the most effective inhibitors. PMID- 4041967 TI - Mammalian lymphocytes: stress-induced synthesis of heat-shock proteins in vitro and in vivo. AB - Mammalian (human, mouse, and rabbit) white blood cells (lymphocytes) maintained in culture respond to a brief incubation at an elevated temperature (at or above 41 degrees C) by (i) the new and (or) enhanced synthesis of a small number of proteins (the so-called heat-shock proteins; HSPs) having molecular masses of approximately 110 000, 100 000, 90 000, 70 000, 65 000, and 26 000 daltons and (ii) the depressed synthesis of proteins normally made at 37 degrees C. The HSPs synthesized in culture by human, rabbit, and mouse (peripheral and splenic) lymphocytes are similar in number, molecular mass, and distribution on two dimensional (isoelectric focusing and sodium dodecyl sulfate--polyacrylamide) electrophoretic gels to those synthesized in vivo by lymphocytes in hyperthermic mice. Since the level of hyperthermia used to induce HSP synthesis in mouse lymphocytes in vitro and in vivo is of a magnitude (41 degrees C) also used to promote thermotolerance in mice and is similar to temperatures attained during febrile episodes in rabbits and in humans, we suggest that the in vitro and in vivo synthesis of HSPs by mouse lymphocytes, demonstrated in this study, represents a relevant, physiological response which mammalian lymphocytes may normally use to survive periods of thermal stress. PMID- 4041968 TI - Effects of cytochalasin B on steroid-induced oocyte meiosis and centrifugally induced nuclear movement in the goldfish Carassius auratus. AB - In goldfish, 17 alpha, 20 beta-dihydroxyprogesterone (DHP) induced oocyte nucleus or germinal vesicle migration (GVM) and dissolution (GVD) in a dose-related fashion. Administration of cytochalasin B (CB) in the presence of DHP inhibited the steroid-induced GVM and GVD after 24 and 48 h of incubation. The presence of CB alone, at concentrations below 25 micrograms/mL, had no effect on GVM or GVD. Furthermore, CB, either alone or in combination with DHP, elicited significant increases in follicular diameter after 24 and 48 h of incubation. To test the effect of CB on ooplasmic viscoelasticity, fully grown follicles were centrifuged and the centrifugally induced germinal vesicle (GV) displacement was determined. Pretreatment (24 h) of follicles with high doses of CB (25 and 50 micrograms/mL) increased the movement of GV in a centripetal direction. However, at lower concentrations (0.005-5 micrograms/mL), CB treatment was without an effect on the centrifugally induced GV movement in the oocyte. The present study suggests involvement of microfilaments or other cytoskeletal components, sensitive to CB, in the mechanisms of GVM and GVD in goldfish oocytes. In addition, a simple technique has been described for testing ooplasmic viscoelasticity determined by movement of the GV under a centrifugal force. PMID- 4041969 TI - On the interaction between 5-hydroxytryptamine and N-acetylneuraminic acid under aqueous conditions. AB - A complex designated 5-HT-NeuAc was formed between 5-hydroxytryptamine (5-HT) and N-acetylneuraminic acid (NeuAc) under aqueous conditions. Complex formation was encouraged by exposure to light (3000-3800 A; 1 A = 0.1 nm) and freeze-drying and the freeze-dried complex was isolated by gel filtration chromatography. Although stable to rechromatography on Bio-Gel P-2 if H2O was the eluent, 5-HT-NeuAc dissociated into the free components when placed in 0.1 M NaCl. Chemical analyses of the isolated complex showed that an equimolar amount of 5-HT and NeuAc was present and that all group functions were intact; these data suggested that the association between 5-HT and NeuAc was noncovalent. Spectrophotometric measurements demonstrated a small increase (approximately 12%) in extinction coefficient (275 nm) and a large increase (340- to 440-fold) in fluorescence emission (340 nm) compared with 5-HT alone. Data obtained from 1H nuclear magnetic resonance spectroscopy (250 MHz) of 5-HT and NeuAc standards compared closely to published reports. In comparison, measurements made with 5-HT-NeuAc showed that all 5-HT protons were slightly deshielded; of the NeuAc protons, slight deshielding of H8 and significant shielding of H3eq, H3ax, and H6 was observed. From these observations, a model describing the association between 5 HT and NeuAc is proposed. PMID- 4041970 TI - Hypereosinophilic syndrome in cats: a report of three cases. AB - The clinical, clinicopathological and pathological findings in three cats with hypereosinophilic syndrome are described. The cats chosen for the study had marked eosinophilia and evidence of tissue infiltration by eosinophils. Necropsies were performed on two cats, biopsy and blood samples were provided for the third cat. At necropsy, there was diffuse reddening of femoral bone marrow with ulceration and thickening of the duodenum. The livers had an enhanced lobular pattern with multiple, white, 1-3 mm nodules throughout the parenchyma. One cat had splenomegaly and the other had several enlarged, white, firm lymph nodes. Histopathologically, there was eosinophil infiltration of intestine, lymph nodes, liver, spleen, adrenal medulla and beneath the endocardium. Ultrastructurally, the eosinophils from lymph node and bone marrow of cat II were morphologically normal. The rigid criteria for eosinophilic leukemia were not fulfilled by these cases and the etiology of the eosinophilia in each case is not known. Possible pathogenic mechanisms are discussed. PMID- 4041971 TI - Interrelationships between ambient temperature, age at calving, postpartum reproductive events and reproductive performance in dairy cows: a path analysis. AB - Path analysis was used to determine the interrelationships between ambient temperature, age at calving, postpartum reproductive events and reproductive performance in dairy cows. The data used in the analysis were collected on 226 Holstein-Friesian cows calving in a commercial dairy herd during a 17 month period (May 1, 1981 to October 1, 1982). The data were obtained from a double blind study evaluating the effects of gonadotrophin releasing hormone and cloprostenol in postpartum cows. Rectal palpation to assess uterine involution and ovarian activity was performed on each cow on days 15, 24 and 28 postpartum. At the same time, blood samples were collected for subsequent progesterone assay. Data were recorded on the occurrence of reproductive diseases and events from the time of parturition until the diagnosis of pregnancy or until the cow left the herd in the case of culled cows. There was an increase in the incidence of retained placenta, in the percentage of cows with abnormal vaginal discharge in the early postpartum period as well as a delay in uterine involution during the winter months. In addition, cows calving during the winter had prolonged intervals to first estrus, first service and conception compared to cows calving during the summer. (Cows calving during the warmest months, on average, were seen in estrus 24 days sooner, received first service 42 days sooner and conceived 27 days sooner than cows calving during the coldest months of the year).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4041972 TI - Salmonellae and salmonellosis in captive reptiles. AB - In a survey of 150 pet reptiles submitted for necropsy, 51% of snakes, 48% of lizards and 7% of turtles were infected with Salmonella. About one third of the positive animals had died due to various manifestations of salmonellosis. Thirty one Salmonella serotypes were identified including three isolates new to Canada. The public health implications are discussed in view of the restricted popularity of reptiles and their possible infection from domestic agricultural products. PMID- 4041973 TI - Sequential morphological and quantitative changes in blood and bone marrow neutrophils in dogs with acute inflammation. AB - Blood and bone marrow morphology were studied sequentially in dogs during experimental inflammation induced by intramuscular injection of turpentine. Depletion of the bone marrow storage pool of mature neutrophils and an increase in mitotic activity and number of early granulocyte precursors were evident within 24 hours. During the next three days, intense granulocytic hyperplasia resulted in replenishment of the bone marrow storage pool. Neutrophils with foamy vacuolation and increased basophilia of the cytoplasm (toxic neutrophils) were present in the blood by eight hours postinjection. The number of toxic neutrophils paralleled the intensity of clinical signs and changes in rectal temperature but not the number of band neutrophils. This indicates that changes in number of toxic neutrophils in sequential leukograms can be a prognostic indicator in dogs with severe inflammation. PMID- 4041974 TI - The concentrations of copper, zinc, manganese and selenium in the hair of newborn piglets and their dams. AB - Instrumental neutron activation analysis was employed to determine the levels of certain trace elements in the hair of newborn piglets and their dams. The mean concentrations (mumoles/mg) of copper, zinc, manganese and selenium in the neonatal piglet hair samples were 222 +/- 55, 4940 +/- 1728, 12.7 +/- 17.1 and 8.9 +/- 5.5, respectively, and in sow hair samples the mean concentrations (mumoles/mg) were 156 +/- 22, 5124 +/- 1927, 31.7 +/- 22.2 and 6.5 +/- 3.7, respectively. The mean copper level was higher (p less than 0.05) in piglet hair compared with sow hair. However the mean concentration of manganese was lower (p less than 0.05) in piglet hair. There was no relationship between the trace mineral levels found in the piglets' hair and the dams' hair. The levels of copper, zinc, manganese and selenium found in piglet hair were shown to be unrelated to the piglet body weight. The feasibility of using porcine hair as a practical biopsy material for trace element analysis is discussed. PMID- 4041975 TI - Piglet blood glutathione peroxidase levels and preweaning mortality. AB - The blood glutathione peroxidase levels of one day old piglets from 22 litters were examined. Body weight and piglet survival were monitored in order to assess the relationship between these two factors and blood glutathione peroxidase activity. The mean blood glutathione peroxidase level of one day old piglets (65 mu/gHb) was significantly lower (p0.001) than the mean level (85 mu/gHb) at weaning. The mean blood glutathione peroxidase activity of one day old piglets was not related to the size of the litter, but was related (p less than 0.1) to the mean litter blood glutathione peroxidase level at weaning time. Piglet blood glutathione peroxidase was not related to piglet body weight. The blood glutathione peroxidase level of the sows at one-day post-farrowing was not related to the mean blood glutathione peroxidase activity of their litters at one day of age but was correlated (p less than 0.1) with the mean blood glutathione peroxidase levels of their litters at weaning. Piglet viability was shown to be strongly correlated (p less than 0.001) with body weight at one day of age. The blood glutathione peroxidase level of one day old piglets was weakly associated (p less than 0.1) with piglet survival. Further work is required to clarify this latter observation, which suggests that selenium supplementation to newborn piglets may be beneficial regardless of the dams nutritional status. PMID- 4041976 TI - Pathology of acute 3-acetyldeoxynivalenol toxicity in mice. AB - Mice were killed 2, 4, 6, 12, 24, 48 and 96 hours after intragastrical administration of 0, 5, 10, 20, or 40 mg/kg body weight of 3 acetyldeoxynivalenol. The animals became clinically ill after 12 hours and some animals in the highest dose group died. Histological examination of duodenal crypts, thymus and spleen revealed, in all dose groups, presence of the characteristic lesions that are known to be produced by trichothecenes, but the intensity of lesions in the 40 mg group corresponded to lesions known to be caused by 4 mg/kg of T-2 toxin. A rabbit skin bioassay with 3 acetyldeoxynivalenol gave negative results on one occasion and a mild reaction to 100 to 500 micrograms/mL on another. It is concluded that 3-acetyldeoxynivalenol is considerably less toxic than T-2 toxin, but causes acute effects in the dividing cells of the body in a manner characteristic of trichothecenes. PMID- 4041977 TI - Tracheal versus pulmonary deposition and clearance of inhaled Pasteurella haemolytica or Staphylococcus aureus in mice. AB - The aim of this investigation was to do a comparative study on the deposition and clearance of inhaled bacteria between the lungs and tracheae of mice exposed to aerosols of bacteria. Two hundred and eighty-eight mice were divided into four groups (n = 72) and exposed to aerosols of Pasteurella haemolytica or Staphylococcus aureus in four replicates. The numbers of bacteria were determined in the trachea and lungs of mice sacrificed 0, 2, 4, 8, 12, 24, 48 and 72 hours postexposure. Results indicated that bacterial deposition was greater in lungs than in tracheae. No significant (p greater than 0.05) difference was observed between P. haemolytica and S. aureus clearance rates. Although bacteria were rapidly eliminated from the whole respiratory tract, bacterial clearance was significantly (p less than 0.002) faster in tracheae than lungs. A significant (p less than 0.05) replicate effect was also observed. PMID- 4041979 TI - The sensitivity and specificity of postbreeding plasma progesterone levels as a pregnancy test for dairy cows. AB - Plasma progesterone levels on day 4 and day 8 postbreeding were measured for one hundred and eighty-four dairy cows. These two parameters (PPD4, PPD8), their absolute difference (PPDIFF) and their ratio (PPRATIO) were assessed for their ability to identify cows not conceiving, using the principles of sensitivity and specificity. PPD4 was significantly higher (p less than 0.10) and PPD8, PPDIFF and PPRATIO were significantly lower (p less than 0.01) in cows remaining open than in pregnant cows. Evaluating each parameter separately, PPDIFF greater than 3.00 units had the highest specificity, 85.7%, but a low sensitivity (27.0%). Combining two parameters using series interpretation to increase specificity resulted in the best combination of specificity (87%) and sensitivity (27%). Maximum specificity was 97% for PPD4 less than or equal to 1.00 units and PPD8 greater than 4.00 units, and also for PPD4 less than or equal to 1.00 units and PPDIFF greater than 3.00 units, but sensitivity was very low (7% and 10% respectively). Predictive values of the test results with the best specificity were evaluated; given the population pregnancy rate of 54%, none exceeded 50%, indicating that the plasma progesterone parameters were not very useful for identifying open dairy cows. PMID- 4041978 TI - Pulmonary recruitment of neutrophils and bacterial clearance in mice inoculated with aerosols of Pasteurella haemolytica or Staphylococcus aureus. AB - Pulmonary alveolar macrophages are considered to be the main phagocytic cell of the pulmonary defense mechanism. However recent studies indicate that neutrophils may also participate in the defense against inhaled bacteria. The aim of this investigation was to study in mice the correlation between numbers of phagocytic cells in the bronchoalveolar space and the pulmonary clearance of bacteria. White mice were exposed to aerosols of Pasteurella haemolytica (n = 129) or Staphylococcus aureus (n = 129) in three different experimental replicates. Another group of mice (n = 22) was sham exposed to an aerosol of sterile phosphate buffered solution in a single replicate. Animals were sacrificed at various times postaerosolization. The numbers of neutrophils and alveolar macrophages in lung lavages and the pulmonary bacterial clearance rates were determined and statistically analysed. No significant differences (p greater than 0.05) were observed in the rates of pulmonary clearance between the two genera of bacteria, but P. haemolytica had a significant (p less than 0.05) replicate effect. The number of alveolar macrophages was not significantly affected by either bacteria or phosphate buffered solution. Exposure to P. haemolytica resulted in dramatic, significant (p less than 0.01) but transient increases in neutrophils in the bronchoalveolar space as well as a significant (p less than 0.01) increase in the weights of lung. The correlation between neutrophils and clearance was positive for P. haemolytica but negative for S. aureus. These results indicate that both species of bacteria are rapidly eliminated from the lung despite a rather different cellular response. PMID- 4041980 TI - Intraocular penetration of netilmicin. AB - The intraocular penetration of the aminoglycoside netilmicin following intramuscular and subconjunctival injection was studied in 102 patients undergoing elective cataract surgery. Those who received either a single 1.5 mg/kg intramuscular injection or two 1.5-mg/kg injections 6 hours apart subsequently had therapeutic serum levels but aqueous levels of less than 2.4 micrograms/mL. Those who received a subconjunctival injection of either 12.5 or 25 mg of netilmicin subsequently had aqueous levels of up to 36 or 85.6 micrograms/mL; therapeutic levels in the anterior chamber persisted for 7 to 9 hours, with higher levels following the 25-mg injection. Despite wide variation in the aqueous levels following subconjunctival injection the ocular penetration of netilmicin was comparable to that reported for other aminoglycosides. No major complications were associated with the use of this antibiotic by either route. PMID- 4041981 TI - Ocular and oculodermal melanocytosis. AB - Thirty-three cases of ocular (27) or oculodermal (6) melanocytosis were reviewed to determine the ocular structures involved by the melanocytic hyperpigmentation. The hyperpigmentation was clinically documented to involve all quadrants of the eye in the majority of the subjects; however, nine persons had sectorial involvement. The choroid and episclera were involved diffusely or sectorially in all the subjects, and the anterior chamber angle and iris were involved in most cases. The conjunctiva, lens and optic disc were less frequently involved. Ten persons had a uveal malignant melanoma in the hyperpigmented eye, and in three of the cases the melanoma had arisen in the hyperpigmented sector. Melanocytic involvement of the trabecular meshwork was not clinically correlated with elevated intraocular pressure. PMID- 4041982 TI - Electron microscopic study of toxicity of intravitreal injections of gentamicin in primates. AB - Seven eyes of four young adult cynomolgus monkeys were injected intravitreally with 0.4 mg of gentamicin. One eye was enucleated after 1 day, and two eyes were enucleated after 1 week, 2 weeks and 1 month. The control eye received an intravitreal injection of 0.1 mL of saline and was enucleated after 1 week. All the eyes underwent electroretinography and ophthalmoscopy before and after treatment. No differences were detected by these techniques or by light and electron microscopy between the experimental eyes and the control. PMID- 4041983 TI - Phthisis bulbi after intraocular lens implantation in a child. AB - A 4-year-old boy with trisomy 21 and a congenital cataract underwent cataract extraction and implantation of an iris-supported intraocular lens (IOL). Four years later the implant dislocated anteriorly and had to be removed. Now, 11 years postoperatively, the eye is blind, painful and shrunken. IOL implantation in infants and children is theoretically justified to preserve vision, reduce amblyopia and preserve fusion. The use of modern posterior chamber IOLs, especially when implanted in the lens capsular bag (if technically feasible), could reduce the risk of complications. However, until further data are accumulated, a conservative approach is warranted. PMID- 4041984 TI - Sugar uptake into a primary culture of dog kidney proximal tubular cells. AB - We describe the functional characteristics of a new primary culture system derived from a suspension of dog proximal tubular cells. The culture system is maintained on alpha minimal essential medium with 15% fetal calf serum supplementation. At confluency the cultured cells demonstrate the following: (i) typical epithelial morphology using light microscopy, with multiple dome formation inhibited by ouabain; (ii) strong binding with a polyclonal antibody directed against dog proximal tubular brush border membrane antigens; (iii) high concentration of alkaline phosphatase activity by histochemical staining; and (iv) 25-hydroxycholecalciferol (25(OH)D3)-24-hydroxylase activity. Sugar transport was assessed using alpha-methyl-D-glucopyranoside (alpha MG), a nonmetabolizable analog of D-glucose, as well as L-glucose, and 3-O-methyl-D glucose (3OMG). The transport of alpha MG was stereospecific; temperature sensitive; inhibited strongly by phlorizin but not by cytochalasin B, phloretin, or 3OMG; and Na dependent. The transport of 3OMG is stereospecific, temperature sensitive, and inhibited strongly by phloretin and cytochalasin B, but not by phlorizin. Despite the apparent heterogeneity of cell type, this primary culture system exhibits many features of normal dog proximal tubule function. PMID- 4041985 TI - The conditioning effect of large doses of ascorbic acid in guinea pigs. AB - The influence of prolonged exposure of guinea pigs to excessive ascorbic acid (AA) on the outcome of pregnancy, as well as the adaptive effect of the vitamin either during preweanling life or following weaning, were examined. Continuous exposure to AA (1 mg/mL drinking water) from the time they were first mated up to the time of second pregnancy, had no significant effect on the number of offspring and on their weights at birth, when compared with that of the animals receiving 0.1 mg AA/mL drinking water. However, change in AA intake from 1 to 0.1 mg/mL drinking water, at the age of 21 days, resulted in a significant loss in body weight and reductions in the plasma, leukocyte, and adrenal concentrations of AA, as compared with those of the pair-fed animals receiving 0.1 mg/mL drinking water throughout. The present study also indicated that the conditioning effect is less pronounced in guinea pigs when exposed to the high AA following weanling age than in utero. PMID- 4041986 TI - Postabsorption antidotal effects of N-acetylcysteine on acetaminophen-induced hepatotoxicity in the mouse. AB - Male Swiss Webster mice, treated with N-acetylcysteine (NAC, 500 mg/kg po) 1 h following acetaminophen (NAPA, 350 mg/kg po) administration, had control levels of transaminases indicating that NAC protects against NAPA-induced hepatotoxicity by postabsorption antidotal mechanism(s). Hepatic congestion induced by NAPA was reduced by NAC. Significantly higher elimination rate constants (K) for indocyanine green (500 micrograms/kg, iv) in mice treated with NAPA and NAC (K = 0.676 +/- 0.062) than in animals receiving NAPA alone (0.341 +/- 0.105) suggested NAC improved or preserved the hepatic circulation of the compromised liver. This NAC-induced improvement and (or) preservation of hepatic circulation was reflected in biliary and urinary excretion of acetaminophen and its metabolites by a general increase in elimination during the first 6 h (70.2 +/- 2.6 vs. 32.6 +/- 7.1%), and in the repletion of glutathione (GSH) in the liver by a return to control levels more quickly (3 vs. greater than 5 h) following depletion by NAPA. The metabolic consequences of the postabsorption antidotal effect of NAC in the compromised liver was a preferential excretion of sulphydryl-derived metabolites in the 1-4 h bile (GSH conjugate 11.30 +/- 1.25 vs. 7.25 +/- 0.39%) which was subsequently observed in the urine by preferential excretion of glutathione degradation products. PMID- 4041987 TI - A comparative study of the inhibition of hepatic aldehyde dehydrogenases in the rat by methyltetrazolethiol, calcium carbimide, and disulfiram. AB - Methyltetrazolethiol (1-methyl-5-mercapto-1,2,3,4-tetrazole, MTT) is a heterocyclic substituent of the cephalosporin antibiotics, cefamandole, cefoperazone, and moxalactam. Pretreatment of rats with MTT has been reported to increase blood acetaldehyde concentration after ethanol administration. The time course of MTT-induced inhibition of hepatic aldehyde dehydrogenases (ALDH) was determined in adult, male Sprague-Dawley rats in comparison with the hepatic ALDH inhibition induced by calcium carbimide (calcium cyanamide, CC) and disulfiram (D). The apparent onset of maximal inhibition of hepatic low Km ALDH occurred at 2 h for 50 mg/kg MTT (subcutaneous, s.c.) and 7 mg/kg CC (oral) and at 24 h for 300 mg/kg D (oral). The relative magnitude of maximal inhibition of low Km ALDH was CC greater than D greater than MTT. The relative duration of enzyme inhibition was D greater than MTT greater than CC. High Km ALDH was only inhibited by CC. Hepatic low Km ALDH was selectively inhibited by s.c. and oral administration of 125 mg/kg MTT. For s.c. administration of 125 mg/kg MTT, the magnitude of maximal enzyme inhibition and the duration of inhibition were greater than for the 50 mg/kg dose. Oral administration of 125 mg/kg MTT produced similar inhibition of hepatic low Km ALDH compared with s.c. administration of the same dose. The time course of blood ethanol and acetaldehyde concentrations was determined for the intravenous infusion of two 0.3-g/kg doses of ethanol to rats that were pretreated orally with saline (1 h), MTT (125 mg/kg, 2 h), or CC (7 mg/kg, 1 h). The relative increase in blood acetaldehyde concentration compared with saline pretreatment was CC greater than MTT. The elimination of ethanol from blood was slower in the MTT- and CC-pretreated animals, and this effect was more pronounced for CC pretreatment. Overall, the data demonstrate that the characteristics of hepatic ALDH inhibition for MTT are different from those of the known ALDH inhibitors, CC and D. PMID- 4041988 TI - The effect of growth hormone on biogenic amines in the hepatic portal circulation of the dog. AB - The effects of a spike concentration of growth hormone (GH) on hepatic portal and peripheral levels of free serotonin and catecholamines were studied by improved radioenzymatic methods in trained, conscious, normal, adult dogs fitted with an indwelling portal catheter. An injection of ovine GH (6 or 100 micrograms/kg) into a cephalic vein produced in the hepatic portal circulation a transient, statistically significant rise of serotonin and a concomitant significant reduction in the concentration of dopamine, norepinephrine, and epinephrine. No change was found in the peripheral circulation, partly because the amines were conjugated to sulfates and glucuronides and these derivatives are not detectable by our assays. Thus, a pulse of GH not only stimulates the release of pancreatic hormones and glucose turnover, but also affects the portal profile of glucoregulatory bioamines. The present investigation lends further support to our view that the splanchnic area represents an endocrine system whose preferential target is the liver. PMID- 4041989 TI - Acetaminophen toxicity in lymphocytes heterozygous for glutathione synthetase deficiency. AB - We have studied the effects of acetaminophen metabolites generated by a murine hepatic microsomal system on lymphocytes from two subjects heterozygous for glutathione synthetase deficiency. Heterozygous cells exhibited greater dose related toxicity than controls. Following a 2-h incubation with acetaminophen and the microsomal system, cells were washed and incubated for 16 h in the presence or absence of N-acetylcysteine, the standard antidote for acetaminophen toxicity. In control cells, glutathione content was replenished to nearly base-line values and toxicity was prevented. N-Acetylcysteine thus prevented toxicity even after covalent binding of acetaminophen metabolites had occurred. Heterozygous cells failed to use N-acetylcysteine as efficiently to resynthesize glutathione, and the cells were not protected from acetaminophen toxicity. Heterozygotes may be at increased risk of toxicity from drugs whose metabolites are detoxified by glutathione conjugation. PMID- 4041990 TI - The effect of insulin deficiency, dietary protein intake, and plasma amino acid concentrations on brain amino acid levels in rats. AB - The effect of diabetes (streptozotocin, 65 mg/kg ip), dietary protein intake (15 60%), and plasma amino acid concentrations on brain large neutral amino acid levels in rats was examined. After 20 days, the plasma concentrations of methionine and the branched chain amino acids (BCAA), valine, isoleucine, and leucine were increased in diabetic rats. In brain tissue, methionine and valine levels were increased but threonine, tyrosine, and tryptophan concentrations were depressed. Increased protein consumption promoted a diabetic-like plasma amino acid pattern in normal rats while enhancing that of diabetic animals. However, with the exception of threonine, glycine, valine, and tyrosine, there was little effect on brain amino acid levels. A good association was found between the calculated brain influx rate and the actual brain concentration of threonine, methionine, tyrosine, and tryptophan in diabetic animals. There was no correlation, however, between brain influx rate and brain BCAA levels. Thus, the brain amino acid pattern in diabetes represents the combined effects of insulin insufficiency and composition of the diet ingested on plasma amino acid levels as well as metabolic adaptation within the brain itself. PMID- 4041991 TI - Chronic treatment of rats with D-600 causes a compensatory decrease in the calcium requirement for contractility of vascular smooth and cardiac muscles. AB - We studied the effects of chronic hypotensive treatment of normotensive Wistar rats (NWR) with methoxyverapamil (D-600) and hydralazine on in vitro contractile response of aortic strips, portal vein strips, and Langendorff-perfused hearts in normal (2.5 mM) and low (0.2 mM) calcium (Ca). Portal vein strips from rats treated with D-600, compared with the same strips from control and hydralazine treated rats, developed greater spontaneous contractile activity in normal Ca and retained greater responses to norepinephrine (NE) and 80 mM K in low Ca. Aortic strips from all three groups of rats retained similar responses to NE and K in low Ca. Hearts from D-600-treated rats produced less intraventricular pressure (IVP) to isoproterenol (ISO) than hearts from control and hydralazine-treated rats in normal Ca but greater IVP to ISO than hearts from the other two groups of rats in low Ca. Thus, chronic treatment of NWR with D-600 but not with hydralazine resulted in the reduction of Ca requirement for contractile activities of the portal vein and the myocardium. PMID- 4041992 TI - Induction of premature delivery in sheep following infusion of cortisol to the fetus. I. The effect of maternal administration of progestagens. AB - Premature induction of delivery in fetuses infused with graded doses of cortisol was brought about in 123.5 +/- 7.7 h (mean +/- SEM, n = 6) after the start of cortisol infusion. This treatment caused a rise in fetal plasma cortisol similar to that observed at normal delivery. Maternal and fetal progesterone and 20 alpha dihydroprogesterone concentrations decreased to basal levels during infusion of cortisol to the fetus. Induction of premature delivery was delayed or prevented by concomitant treatment of the ewe with progestagen. Maternal intramuscular injection of 100 mg progesterone, 2 times daily, prevented delivery in four of four ewes treated during the time that cortisol was infused into the fetus (11-13 days). Maternal plasma progesterone and 20 alpha-dihydroprogesterone concentrations were maintained during this period, but fetal plasma progesterone concentrations decreased to the same extent as in the fetuses infused with cortisol alone. A single intramuscular injection of 250 mg of medroxyprogesterone acetate to ewes on the day before commencement of infusion of cortisol to the fetus prevented delivery in four of six ewes during the time that cortisol was infused for 9, 13, 14, and 15 days, respectively. One ewe delivered a live lamb at 133.5 h and another at 147.7 h after the start of infusion of cortisol to the fetus. Maternal and fetal plasma cortisol, progesterone, and 20 alpha dihydroprogesterone concentrations were similar to those observed during infusion of cortisol alone to the fetus. Although fetal cortisol concentrations rose in a similar fashion, and to a similar extent, in all three groups during infusion of cortisol to the fetus, fetal 11-desoxycortisol concentrations only rose above basal levels close to the time of delivery in cortisol-infused fetuses or, in the progestagen-treated groups, when the fetus showed signs of being stressed. PMID- 4041994 TI - In situ molecular weight determination of rat brain [3H]phenytoin binding sites. AB - Using irradiation inactivation analysis of specific [3H]phenytoin binding to rat brain we have demonstrated that there are two different binding sites involved, with molecular weights of 73238 +/- 1535 (higher affinity site) and 108121 +/- 6935 (lower affinity site). PMID- 4041993 TI - The role aortic chemoreceptors during severe CO hypoxia. AB - The importance of aortic chemoreceptors in the circulatory responses to severe carbon monoxide (CO) hypoxia was studied in anesthetized dogs. The aortic chemoreceptors were surgically denervated in eight dogs prior to the induction of CO hypoxia, with nine other dogs serving as intact controls. Values for both whole body and hindlimb blood flow, vascular resistance, and O2 uptake were determined prior to and at 30 min of CO hypoxia in the two groups. Arterial O2 content was reduced 65% using an in situ dialysis method to produce CO hypoxia. At 30 min of hypoxia, cardiac output increased but limb blood flow remained at prehypoxic levels in both groups. This indicated that aortic chemoreceptor input was not necessary for the increase in cardiac output during severe CO hypoxia, nor for the diversion of this increased flow to nonmuscle tissues. Limb O2 uptake decreased during CO hypoxia in the aortic-denervated group but remained at prehypoxic levels in the intact group. The lower resting values for limb blood flow in the aortic-denervated animals required a greater level of O2 extraction to maintain resting O2 uptake. When CO hypoxia was superimposed upon this compensation, an O2 supply limitation occurred because the limb failed to vasodilate even as maximal levels for O2 extraction were approached. PMID- 4041995 TI - Specific binding of [3H]phenytoin in the human brain. AB - Competition between cold phenytoin and [3H]phenytoin binding was observed in normal human brain. Binding was observed in all areas examined. The highest number of sites was in the amygdala (a total of 717.71 fmol/mg protein) and the lowest in the Brodman area (BA) 4 of the motor cortex (153.91 fmol/mg protein) and cerebellar cortex (154.4 fmol/mg protein). In three areas, amygdala, cortex area BA 38 (inferior parietal lobe), and cortex area BA 8 (premotor cortex), two sets of binding sites were observed. In these areas the Kd for the higher affinity sites ranged from 35 to 116 nM, and for the lower affinity site, from 328 to 866 nM. In the four areas where only one binding site was observed the KdS ranged from 164 to 311 nM and the Scatchard plot was linear. PMID- 4041996 TI - Nutrition and metabolic development. AB - Perinatal changes in metabolic processes owing to a change from a high carbohydrate to a high fat (milk) diet at birth are described. It is pointed out that early changes in food composition may have permanent effects and it is suggested that, in the rat, this may be due to structural alterations in the brain at a time when it is still differentiating. Such changes are irreversible. PMID- 4041997 TI - The 13th J. A. F. Stevenson memorial lecture. Sexual differentiation of the brain: possible mechanisms and implications. AB - The mammalian brain appears to be inherently feminine and the action of testicular hormones during development is necessary for the differentiation of the masculine brain both in terms of functional potential and actual structure. Experimental evidence for this statement is reviewed in this discussion. Recent discoveries of marked structural sex differences in the central nervous system, such as the sexually dimorphic nucleus of the preoptic area in the rat, offer model systems to investigate potential mechanisms by which gonadal hormones permanently modify neuronal differentiation. Although effects of these steroids on neurogenesis and neuronal migration and specification have not been conclusively eliminated, it is currently believed, but not proven, that the principle mechanism of steroid action is to maintain neuronal survival during a period of neuronal death. The structural models of the sexual differentiation of the central nervous system also provide the opportunity to identify sex differences in neurochemical distribution. Two examples in the rat brain are presented: the distribution of serotonin-immunoreactive fibers in the medial preoptic nucleus and of tyrosine hydroxylase-immunoreactive fibers and cells in the anteroventral periventricular nucleus. It is likely that sexual dimorphisms will be found to be characteristic of many neural and neurochemical systems. The final section of this review raises the possibility that the brain of the adult may, in response to steroid action, be morphologically plastic, and considers briefly the likelihood that the brain of the human species is also influenced during development by the hormonal environment. PMID- 4041998 TI - Evidence for a contribution by brown adipose tissue to the development of fever in the young rabbit. AB - This study was undertaken to determine if brown adipose tissue was involved in heat production during fever produced by S. abortus equi (1 micrograms) in unanesthetized rabbits aged 19-26 days. The fever (0.9-1.6 degrees C) occurred after a delay of 20-30 min and was frequently biphasic. Radiolabelled microspheres for measuring tissue blood flow were injected intraventricularly into three groups of animals: rabbits not given pyrogen, rabbits in which the febrile response to pyrogen was developing, and rabbits in which the febrile response had peaked. Blood flow to brown fat deposits and other organs was calculated from the fractional distribution of the microspheres and the recovery of microspheres in a reference arterial blood sample. At the fever peak, blood flow to brown fat was not significantly different (p greater than 0.05) from the control value (0.9 +/- 0.2), but during the rising phase of the fever the flow increased significantly (p less than 0.01) to 2.6 +/- 0.4 mL min-1 g-1. The blood flow to muscles of the forelimbs and hind limbs was also increased significantly (p less than 0.05) during the rising phase of the fever. No significant change in blood flow to other organs or tissues was found during the rising phase of the fever. These results indicate that both nonshivering as well as shivering thermogenesis contribute to heat production during development of fever in the young rabbit. However, nonshivering thermogenesis was not involved in the maintenance of the elevated body temperature after the fever had peaked. PMID- 4041999 TI - Peripheral and central mechanisms of the pressor response elicited by stimulation of the locus coeruleus in the rat. AB - Electrical stimulation of the pontine nucleus locus coeruleus (LC) caused an increase of the arterial blood pressure in anesthetized rats, and elevated plasma noradrenaline (NA) and adrenaline (A) levels. The stimulation-induced pressor response was characteristically biphasic and consisted of a sharp rise in arterial pressure at the onset of the stimulation, followed by a second elevation at the end of the stimulus. Bilateral adrenalectomy or adrenal demedullation completely blocked the secondary phase of the pressor response elicited by stimulation, but did not affect the primary phase. The latter was specifically eliminated by the destruction of the peripheral sympathetic vasomotor axons with intravenous 6-hydroxydopamine (6-OHDA). The active sites eliciting the secondary adrenomedullary pressor component appeared to be restricted to the nucleus LC, whereas the primary sympathetic vasomotor response could be elicited from sites in and around the nucleus. After brain transection at the midbrain level, stimulation of LC failed to evoke the adrenomedullary pressor response, while the sympathetic vasomotor component was not affected. Similarly, destruction of brain NA neurons by intraventricular administration of 6-OHDA did not change the sympathetic vasomotor response, but virtually abolished the adrenal response. The results demonstrate that the pressor response to stimulation of LC in the rat is due to both increased sympathetic vasomotor activity and CA released from the adrenal medulla. The study also provides evidence suggesting that the noradrenergic LC cell group play an important role in the activation of the adrenal medulla, but is not essential for the activation of the sympathetic vasoconstrictor fiber system. PMID- 4042000 TI - Rat skeletal muscle triacylglycerol utilization during exhaustive swimming. AB - The utilization of triacylglycerol in slow oxidative, fast oxidative-glycolytic, and fast glycolytic skeletal muscle fiber types was examined in rats subjected to a prolonged exhaustive swim. Significant reductions of intramuscular triacylglycerol occurred following 2 h and 40 min of swimming in all muscles containing a predominance of slow oxidative and fast oxidative-glycolytic fibers, which possess a high capacity for free fatty acid oxidation. Triacylglycerol content in the soleus decreased by 48%, and reductions of 41, 29, and 27% were measured in the red vastus lateralis, red gastrocnemius, and plantaris muscles, respectively. In the white vastus lateralis and white gastrocnemius muscles (fast glycolytic fibers) triacylglycerol concentrations were unaffected. In all muscles the variability of intramuscular triacylglycerol measurements between animals was 20-50% and the within animal variance (right vs. left hindlimb) was similar. Analytical repeatability was approximately 10% in all muscles and significantly less than the between- and within-animal variances. It was concluded that a real biological variation exists in the triacylglycerol content of all rat skeletal muscles and that intramuscular triacylglycerol is an important energy source during prolonged exercise of moderate intensity. PMID- 4042001 TI - The renal handling of human urinary ribonuclease by rat kidneys. AB - The purpose of the study was to find out how poly(C)-avid human urinary ribonuclease is handled by the kidney. Purified human urinary ribonuclease (molecular weight 33 000) was radiolabelled with 125I. The enzyme was injected intravenously into dogs and monkeys with and without kidneys. The disappearance rate from the animals without kidneys was markedly prolonged. In the dog and monkey with kidneys, the radiolabelled enzyme which was infused was recovered in the urine unchanged. No large molecular weight fragments were found. When 125I labelled ribonuclease was infused into rats the material recovered in the urine was primarily identical with the material infused. A very small fraction of the material recovered was found to contain some fragments which had chromatographic characteristics of monoiodotyrosine and diiodotyrosine. Two other fragments were detected but could not be identified. Autoradiographic studies of the rat kidneys also showed some reabsorption of the radiolabelled ribonuclease, particularly in the proximal tubules. With electron microscopy the radiolabelled material could be seen in the lysosomes. These observations corroborate findings discovered for other low molecular enzyme such as lysozyme (molecular weight 14 000) and suggest that the human ribonuclease is mainly excreted by the kidneys unchanged and that a minor amount may be reabsorbed by the proximal tubules and metabolized in the lysosomes. PMID- 4042002 TI - Vagal afferent activity and renal nerve release of dopamine. AB - To investigate the involvement of vagal afferents in renal nerve release of catecholamines, we compared norepinephrine, dopamine, and epinephrine excretion from innervated and chronically denervated kidneys in the same rat. The difference between innervated and denervated kidney excretion rates was taken as a measure of neurotransmitter release from renal nerves. During saline expansion, norepinephrine excretion from the innervated kidney was not statistically greater than from denervated kidneys. Vagotomy increased norepinephrine release from renal nerves. Thus vagal afferents participated in the suppression of renal sympathetic nerve activity during saline expansion. No significant vagal control of dopamine release by renal nerves was detected under these conditions. Bilateral carotid ligation stimulated renal nerve release of both norepinephrine and dopamine in saline-expanded rats. The effects of carotid ligation and vagotomy were not additive with respect to norepinephrine release by renal nerves. However, the baroreflex-stimulated renal nerve release of dopamine was abolished by vagotomy. Electrical stimulation of the left cervical vagus with a square wave electrical pulse (0.5 ms duration, 10 V, 2 Hz) increased dopamine excretion exclusively from the innervated kidney of hydropenic rats. No significant change in norepinephrine excretion was observed during vagal stimulation. Increased dopamine excretion during vagal stimulation was associated with a larger natriuretic response from the innervated kidney than from its denervated mate (p less than 0.05). We conclude that under appropriate conditions vagal afferents stimulate renal release of dopamine and produce a neurogenically mediated natriuresis. PMID- 4042003 TI - Effects of thyroid and growth hormone deficiency, and food restriction on heart mass, with and without added stress (carboxyhemoglobinemia). AB - The roles of thyroid and growth hormone, and food restriction in maintenance of heart mass and in carbon monoxide-stimulated cardiac growth were examined. First, thyroidectomized and normal adult male rats inhaled up to 500 ppm CO in air for 42 days. Combined ventricular weights of thyroidectomized rats inhaling CO and air were 12 and 23% smaller than predicted, respectively, while the combined ventricular weight of normal rats inhaling CO was 29% larger than predicted. Thyroidectomy increased the mass of the left ventricle relative to the right ventricle; this was reversed by CO treatment. While the hematocrit increased in thyroidectomized-CO rats, it was lower than in normal-CO rats: likewise the hematocrit of thyroidectomized-AIR rats was lower than that of normal rats in air. Body weights of the thyroidectomized rats were 57% that of normals. As additional controls, two groups of normal rats (one AIR, one CO) were maintained at the same body weight as the thyroidectomized rats, by adjusting food intake. Combined ventricular weight was less than predicted in AIR rats and failed to increase in CO animals, while hematocrits were the same as normals in air and in CO. Serum thyroxine (T4) and growth hormone levels assayed in thyroidectomized rats were less than 15 and 25% of normal rats, respectively. Growth hormone levels were not altered by CO inhalation in thyroidectomized and in normal rats. Levels of both hormones were normal in food-restricted rats. While thyroidectomy produced cardiac atrophy, cardiac growth was stimulated by CO inhalation, although heart mass then only approached that of normals in air. Food restriction also produced cardiac atrophy, but CO inhalation failed to stimulate heart growth. PMID- 4042004 TI - Transient inhibition of the muscarinic actions of carbachol during reactivation of the electrogenic sodium pump in guinea pig taenia caeci smooth muscle. AB - In guinea pig taenia caeci smooth muscle the muscarinic receptor stimulant carbachol evoked depolarization and contraction, which was followed by hyperpolarization and relaxation on its removal. Both the hyperpolarization and relaxation were inhibited by removal of K+ from the external medium. During Na+ pump blockade (K+-free solution) the depolarizing and contracting actions of carbachol decreased. When the Na+ pump was switched on again by readmission of 5.9 mmol/L K+ to K+-depleted and Na+-enriched preparations, electrogenic hyperpolarization and relaxation developed. During this period carbachol failed to produce depolarization and contraction. PMID- 4042005 TI - Force-velocity relationships in hypertensive arterial smooth muscle. AB - Increased total peripheral resistance is the cardinal haemodynamic disorder in essential hypertension. This could be secondary to alterations in the mechanical properties of vascular smooth muscle. Adequate study has not been made of the force-velocity (F-V) relationship in hypertensive arterial smooth muscle. Increased shortening in arterial smooth muscle would result in greater narrowing of arteries. The objectives of this investigation were to see if there is (i) increased shortening or increased maximum change in muscle length (delta Lmax where L stands for muscle length), (ii) an increased maximum velocity of shortening (Vmax) measured in l omicron per second where l omicron is the optimal muscle length for tension development, and (iii) a difference in maximum isometric tension (P omicron) developed in spontaneously hypertensive rat (SHR; N = 6) compared with normotensive Wistar Kyoto rat (WKY;N = 5) caudal artery strips. An electromagnetic muscle lever was employed in recording force-velocity data. Analysis of these data revealed the following: (a) the SHR mean P omicron of 6.21 +/- 1.01 N/cm2 was not different from the mean WKY P omicron of 6.97 +/- 1.64 N/cm2 (p greater than 0.05); (b) the SHR preparations showed greater shortening for all loads imposed; (c) the SHR Vmax of 0.016 l omicron/s was greater than the WKY Vmax of 0.013 l omicron/s (p less than 0.05). This study provides evidence that while hypertensive arterial smooth muscle is not able to produce more force than normotensive arterial smooth muscle, it is capable of faster and greater shortening. The latter could result in increased narrowing of hypertensive arteries and increased blood pressure. PMID- 4042006 TI - Tension-velocity relationships in hypertensive mesenteric resistance arteries. AB - Increased total peripheral resistance is the cardinal haemodynamic disorder in essential hypertension. This could be secondary to alterations in the mechanical properties of vascular smooth muscle. Adequate study has not been made of the tension-velocity (T-V) relationship in hypertensive resistance arterial smooth muscle. Increased narrowing in such arteries would result in increased resistance. The objectives of this investigation were to determine whether there is (i) increased narrowing capacity (-delta C/C omicron, where C stands for arterial internal circumference and C omicron is the optimal arterial internal circumference for maximum tension development); (ii) an increased maximum velocity of isobaric narrowing (Vmax) measured in C omicron per second; (iii) an increased wall thickness (h); and (iv) an increased active stress development (Tmax) in the spontaneously hypertensive rat (SHR; n = 5) compared with the normotensive Wistar Kyoto (WKY; n = 5) and MK-421 (an angiotensin I converting enzyme inhibitor) treated spontaneously hypertensive rat (MK-421 trt. SHR; n = 5) mesenteric resistance (diameter, less than 300 micron) arteries. Analysis of the data for arteries constricting isobarically against a range of pressures revealed that (a) the SHR -deltaC/C omicron values at pressures ranging from 20 to 120 mmHg (1 mmHg = 133.322 Pa) showed significantly increased narrowing compared with the MK-421 trt. SHR and WKY -deltaC/C omicron values in this same pressure range (p less than 0.01), and (b) the SHR derived Vmax of 0.83 +/- 0.08 C omicron/s was significantly faster than either the MK-421 trt.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4042007 TI - Changes in isometric contractile properties of extensor digitorum longus and soleus muscles of C57BL/6J mice following denervation. AB - In this study, conducted on mice of the C57BL/6J+/+ strain, we investigated the differential effects of denervation on the isometric contractile properties of the extensor digitorum longus (EDL) and soleus (SOL) muscles. The contractile properties were studied at 1, 28, 84, and 210 days following unilateral section of the sciatic nerve at 12 weeks of age. When isometric tetanus tension was expressed relative to wet weight, the denervated SOL showed an earlier and more pronounced loss in tension generating capacity than the EDL. Both the denervated SOL and EDL showed potentiation of the twitch tension at 28 days postdenervation. The time to peak twitch tension (TTP) and the time to half-relaxation (1/2RT) were prolonged by 28 days postdenervation in both muscles. This trend continued to the oldest age-groups studied in the EDL, but reached an apparent plateau in the SOL at 84 days postdenervation. In response to fatigue, the denervated SOL showed a marked decrease in resistance to fatigue at 1 day but a relatively normal response thereafter, whereas the denervated EDL showed an increase in resistance to fatigue at and beyond the 28-day period. In spite of the fact that the total contraction time of both muscles increased following denervation, the predominantly oxidative SOL remained a slower contracting muscle than the more glycolytic EDL. PMID- 4042008 TI - Activity of in situ middle cervical ganglion neurons in dogs, using extracellular recording techniques. AB - Neuronal activity in the in situ middle cervical ganglion of dogs was investigated using extracellular recording techniques. The recorded action potentials were frequently active during specific phases of the cardiac cycle, particularly during systole, and this activity persisted following acute decentralization of the ganglion. The activity of these action potentials was modified when systemic arterial pressure was altered by isoproterenol, noradrenaline, adrenaline, or partial occlusion of the aorta, whether in the intact or acutely decentralized preparation. These neurons were active between systolic pressures of 70 and 180 mmHg (1 mmHg = 133.322 Pa). Action potentials were frequently modified by mechanical distortion of the superior vena cava, ventricular epicardium, or adventitia of the aorta, whether the preparation was acutely decentralized or not. Seventy percent of these action potentials were unaffected by stimulation (1 ms, 4 V, 0.5 Hz) of a cardiopulmonary nerve and 27% were suppressed by such stimulation. Five of the neurons were activated by such stimulation. It is presumed that the latter neurons had axons in a cardiopulmonary nerve and most likely were efferent sympathetic postganglionic neurons. Sixty-three percent of these spontaneously active phase-locked units were modified by stimulation of a ramus or an ansa. It is postulated that some of the neurons in the middle cervical ganglia can be modified by afferent axons arising from receptors in thoracic organs, in particular from the great vessels and heart, whether in an intact or acutely decentralized preparation. The majority of these neurons are presumed not to be afferent neurons or efferent postganglionic neurons, as they are not activated directly by electrical stimulation of axons in cardiopulmonary nerves. Rather they are presumed to be interneurons. These results lend support to the thesis that considerable integration of neuronal activity related to thoracic cardiovascular dynamics occurs within the middle cervical ganglia of dogs. PMID- 4042009 TI - The use of 8-phenyltheophylline as a competitive antagonist of adenosine and an inhibitor of the intrinsic regulatory mechanism of the hepatic artery. AB - Reduction of portal blood flow results in compensatory vasodilation of the hepatic artery, the hepatic arterial buffer response. The hypothesis tested is that the regulation of the buffer response is mediated by adenosine, where the local concentration of adenosine in the region of the hepatic arterial resistance vessels is regulated by washout of adenosine into portal venules that are in intimate contact with hepatic arterioles. In anesthetized cats, portal flow was reduced to zero by complete occlusion of all arterial supply to the guts. The resultant dilation of the hepatic artery compensated for 23.9 +/- 4.9% of the decrease in portal flow. Dose-response curves were obtained for the effect of intraportal adenosine infusion on hepatic arterial conductance in doses that did not lead to recirculation and secondary effects on the hepatic artery via altered portal blood flow. The dose to produce one-half maximal response for adenosine is 0.19 mg X kg-1 X min-1 (intraportal) and the estimated maximal dilation is equivalent to an increase in hepatic arterial conductance to 245% of the basal (100%) level. The adenosine antagonist, 8-phenyltheophylline, produced dose related competitive antagonism of the dilator response to infused adenosine (but not to isoproterenol) and a similar, parallel antagonism of the hepatic arterial buffer response. If supramaximal blocking doses were used, the hepatic artery showed massive and prolonged constriction with blood flow decreasing to zero. The data strongly support the hypothesis that intrinsic hepatic arterial buffer response is mediated entirely by local adenosine concentration.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4042010 TI - Histamine--whither now? AB - This review presents, from the author's viewpoint, avenues of histamine research likely to produce new information. One potentially useful approach may be to attempt to relate histamine's function to its occurrence in different body tissues such as the pituitary and hypothalamus, the gastrointestinal mucosa, and the bone marrow and white blood cells. Prospects also seem bright for quantitative studies of histamine metabolites in blood and urine and possible changes in the relative amounts of these metabolites in a variety of diseases. PMID- 4042011 TI - Temperature and histamine receptor function--what is really happening? AB - Early studies suggested that a low temperatures there was a transition of receptor type from an H1 to an H2 receptor when the temperature was reduced from 37 degrees C to temperatures below 20 degrees C. These original observations were based on the development of sensitivity of guinea-pig ileum to the H2 antagonist metiamide as the temperature was reduced. More recently, evidence from a number of laboratories has cast doubt on the existence of a simple H1-H2 receptor transition, but there is abundant evidence that there are major changes in the response of a variety of smooth muscle preparations to histamine at reduced temperatures. The evidence in regard to alterations in histamine response at low temperatures is reviewed, some new evidence presented, and a model which is consistent with most of the observations is suggested. PMID- 4042012 TI - Quantitative determination of histamine metabolites by capillary gas chromatography. AB - A method using capillary gas chromatography is described for the determination of histamine and eight of its basic and acid metabolites in a single biological sample of serum, urine, or gastric juice. Ion-exchange chromatography and extraction with organic solvents are used for isolation and purification, and gas chromatography for identification and quantitation. The heptafluorobutyryl derivatives of histamine and some basic metabolites are compatible with nitrogen phosphorus and electron capture detection modes and offer an excellent sensitivity (detection limit 0.1 pmol with electron capture). The acid metabolites are quantitated after esterification. The linearity range, the sensitivity, a partial study of reproducibility and typical chromatograms show that the method is adaptable to a variety of applications. PMID- 4042013 TI - Effects of coronary sinus pressure elevation on coronary blood flow distribution in dogs with normal preload. AB - Coronary sinus pressure (Pcs) elevation shifts the diastolic coronary pressure flow relation (PFR) of the entire left ventricular myocardium to a higher pressure intercept. This finding suggests that Pcs is one determinant of zero flow pressure (Pzf) and challenges the existence of a vascular waterfall mechanism in the coronary circulation. To determine whether coronary sinus or tissue pressure is the effective coronary back pressure in different layers of the left ventricular myocardium, the effect of increasing Pcs was studied while left ventricular preload was low. PFRs were determined experimentally by graded constriction of the circumflex coronary artery while measuring flow using a flowmeter. Transmural myocardial blood flow distribution was studied (15-micron radioactive spheres) at steady state, during maximal coronary artery vasodilatation at three points on the linear portion of the circumflex PFR both at low and high diastolic Pcs (7 +/- 3 vs. 22 +/- 5 mmHg; p less than 0.0001) (1 mmHg = 133.322 Pa). In the uninstrumented anterior wall the blood flow measurements were obtained in triplicate at the two Pcs levels. From low to high Pcs, mean aortic (98 +/- 23 mmHg) and left atrial (5 +/- 3 mmHg) pressure, percent diastolic time (49 +/- 7%), percent left ventricular wall thickening (32 +/- 4%), and percent myocardial lactate extraction (15 +/- 12%) were not significantly changed. Increasing Pcs did not alter the slope of the PFR; however, the Pzf increased in the subepicardial layer (p less than 0.0001), whereas in the subendocardial layer Pzf did not change significantly. Similar slopes and Pzf were observed for the PFR of both total myocardial mass and subepicardial region at low and high Pcs. Subendocardial:subepicardial blood flow ratios increased for each set of measurements when Pcs was elevated (p less than 0.0001), owing to a reduction of subepicardial blood flow; however, subendocardial blood flow remained unchanged, while starting in the subepicardium toward midmyocardium blood flow decreased at high Pcs. This pattern was similar for the uninstrumented anterior wall as well as in the posterior wall. Thus as Pcs increases it becomes the effective coronary back pressure with decreasing magnitude from the subepicardium toward the subendocardium of the left ventricle. Assuming that elevating Pcs results in transmural elevation in coronary venous pressure, these findings support the hypothesis of a differential intramyocardial waterfall mechanism with greater subendo- than subepi-cardial tissue pressure. PMID- 4042014 TI - Effect of nonsteroidal anti-inflammatory drugs on the microsomal monooxygenase system of rat liver. AB - The effect of acetylsalicylic acid, ibuprofen, indomethacin, ketoprofen, naproxen, phenylbutazone, and salicylic acid on the microsomal oxidative drug metabolism of rat liver was studied. Pretreatment of the rats with pharmacologic doses of acetylsalicylic acid, indomethacin, and ketoprofen decreased both the demethylase and hydroxylase activities of rat liver microsomes. These effects were paralleled by decreases in microsomal cytochrome P-450 content. The rate of the microsomal reactions was increased after pretreatment with ibuprofen and naproxen but only the former increased the concentration of cytochrome P-450. Phenylbutazone and salicylic acid had no in vivo effect on the hepatic monooxygenase. The addition of 1 mM of ibuprofen, indomethacin, ketoprofen, naproxen, and phenylbutazone to rat liver microsomes inhibit both the aminopyrine N-demethylase and p-nitro-anisole O-demethylase activities. The extent of the inhibition varied between 21 and 73% of the control incubation. Indomethacin, naproxen, and phenylbutazone also decreased the aniline hydroxylase activity to roughly 60% of the control value. Acetylsalicylic acid and salicylic acid had no in vitro effect on the microsomal monooxygenase. The nonsteroidal anti inflammatory drugs produced a reverse type I binding spectrum with oxidized cytochrome P-450; indomethacin and phenylbutazone were the strongest ligands. There is no correlation between the effect of addition of nonsteroidal anti inflammatory drugs to the hepatic microsomal homogenate and their in vivo effect on the monooxygenase activity. PMID- 4042016 TI - Very low density lipoprotein binding to cultured aortic endothelium. AB - Because of very low density lipoprotein's (VLDL) potential atherogenicity and the demonstration that VLDL can bind to other cells, we examined the interaction of human VLDL with cultured porcine aortic endothelium. The lipoprotein-cell interaction had many properties similar to those seen with the binding of a ligand to a cell surface receptor. It was time and temperature dependent, saturable, and reversible. Scatchard analysis of competition data suggested that there may be more than one class of binding site. The affinity of the low affinity site was similar to that for low density lipoprotein (LDL). Also, the capacity of endothelial cells to bind VLDL was similar to that for LDL, when related to apo B (i.e., particle) concentration. Not only was unlabelled VLDL able to compete for VLDL binding sites, but so was LDL and high density lipoprotein (HDL). The maximal competition either by LDL or by HDL was less than that by VLDL. The maximal competition by HDL was more than by LDL. The VLDL binding was dependent on Ca2+. It was not changed by the content of lipoprotein in the medium in which cells were grown prior to the binding studies. These observations suggest that VLDL binding to endothelial cells is similar in some respects, but not in all, to the binding of LDL. Comparison of the data with endothelial cells to previous data with adipocytes also indicated differences between the interaction of these two cell types with VLDL. It is possible that this binding process may be involved in the formation of atherogenic remnants of triglyceride-rich lipoproteins on the endothelial surface of large blood vessels. PMID- 4042015 TI - The effect of lidocaine on lysophosphatidylcholine-induced cardiac arrhythmias and cellular disturbances. AB - The production of arrhythmias in the isolated heart by perfusion with lysophosphatidylcholine has been well documented. However, the role of the lysophospholipid as a physiological factor in the generation of cardiac arrhythmias is not clear. In this study, a pharmacological approach was used to delineate the physiological significance of lysophosphatidylcholine during this cardiac dysfunction. Lidocaine (5-20 mg/L) was found to be effective in the protection of the isolated rat heart from the lysophospholipid-induced arrhythmias at pharmacological concentrations. The effect of lidocaine in the protection of lysophospholipid-induced membrane dysfunction was studied with red blood cells. Lidocaine (2 mg/mL) protected red blood cells from hemolysis in the presence of lysophosphatidylcholine. Lidocaine did not inhibit the binding of the lysophospholipid to the red cell membrane, but inhibited hemolysis in a manner similar to cholesterol. The results are consistent with the postulate that lysophosphatidylcholine is a physiological factor in the pathogenesis of cardiac arrhythmias during myocardial ischemia. PMID- 4042017 TI - Organization of medial elastin at aortic junctions in sheep and lambs. AB - Aortas from four sheep and three fetal lambs were fixed at physiological pressure in 10% neutral buffered formalin. The regions with branches were serially sectioned in either cross or longitudinal section at 7-micron intervals and stained for elastin with Gomori-aldehyde-fuchsin. A large model of one aortointercostal junction was made from Plexiglas to show that bundles of elastin appeared to be continuous from the aorta into the branch. These bundles were then studied from large photomicrographs of the other junctions. At the intercostals and lumbars, the elastin lamellae ran continuously from the outer third of the media into the branch. There was often an added "pad" of elastin and other acellular material on the flow divider (distal lip). The large muscular branches which arose from the abdominal aorta have much less elastin than the intercostals. In them the aortic elastin appears to merge into a raphe on the proximal and lateral sides of the junction, with a very abrupt transition. A "tongue" of muscle from the branch often penetrated into the media of the aorta distally. Occasionally a small acellular cap was seen on the apex of the flow divider. There were few significant differences between the lambs and the sheep, probably because embryologically the arteries develop very early. The proximal and distal lips of all junctions were easily distinguished from each other, and the small and large branches were also different. We suspect these regions may respond differently to pressure, but we did not test this hypothesis. PMID- 4042019 TI - Inhibitory processes of hippocampal CA1 pyramidal neurons following kindling induced epilepsy in the rat. AB - To determine the alterations in cellular function which may contribute to the chronic predisposition of neuronal tissue to epileptiform activity, the membrane properties and inhibitory processes of hippocampal CA1 pyramidal cells were investigated using in vitro slices prepared from commissural-kindled rats. No changes were observed in resting membrane potential, input resistance, spike amplitude, and membrane time constant of "kindled" CA1 pyramidal neurons when compared with controls. There were also no differences between control and kindled preparations in the amplitude of recurrent inhibitory postsynaptic potentials (IPSP) and in the duration of inhibition produced by either alvear (Alv) or stratum radiatum (SR) stimulation. Irrespective of group, repetitive stimulation of the Alv reduced the amplitude of the recurrent IPSP but failed to induce seizurelike activity. On the other hand, repetitive stimulation of SR frequently produced a neuronal burst discharge even though the duration and to some extent the amplitude of orthodromic inhibition was increased. On the basis of these data, it may be suggested that chronic changes in CA1 pyramidal cell membrane properties and transient reductions of inhibitory processes do not underlie the enhanced sensitivity of these neurons to seizure activity associated with kindling. PMID- 4042018 TI - The effect of tryptophan on biogenic amines in the hepatic portal circulation of the dog. AB - Mongrel dogs were fitted with indwelling hepatic portal catheters. After recovery from surgery, experiments were conducted in fasting, unrestrained, fully conscious, normal dogs which were accustomed to handling and withdrawal of blood samples. L-Tryptophan, a specific serotonin precursor, was injected into a saphenous vein, 10 microM/kg body weight, dissolved in saline. Plasma serotonin, dopamine, norepinephrine, and epinephrine were determined by radioenzymatic assays in blood samples withdrawn at frequent intervals for 2 h, simultaneously from the indwelling catheter and from a catheter temporarily inserted into a saphenous vein other than the one used for the injection of tryptophan. The injection of the amino acid caused a significant elevation of the concentration of platelet-free serotonin within 60 min and this was accompanied by a reduction in the concentration of the catecholamines, dopamine, norepinephrine, and epinephrine. The changes occurred only in the portal circulation and were not detected in peripheral blood samples. The results of these experiments indicate the existence of a cause and effect related interdependence between the splanchnic serotonergic and adrenergic systems in that the tryptophan-stimulated increase in serotonergic activity resulted in a concomitant reduction in gut adrenergic activity. PMID- 4042021 TI - Physiologic modulations of the systolic time intervals in the fetal lamb. AB - To examine the modulation of fetal systolic time intervals of the ovine fetus in relation to fetal maturation, heart rate, respiratory activity, and circadian rhythm, studies were carried out on 13 fetal-maternal sheep preparations. The data obtained showed that there was a significant correlation between the ejection time (ET) and the RR intervals of the electrocardiogram. The pre ejection period (PEP) and PEP/ET increased in relation to the fetal maturation (38 ms and 0.25 at 120 days to 52 ms and 0.33 at 145 days of gestation, respectively). When the circadian rhythmicity was analyzed, a relative tachycardia was in evidence during the 21- to 03-h period but systolic time intervals remained unchanged. Except for some tachycardia and cardiac rhythm variability, respiratory activity also had no influence on the systolic time intervals. PMID- 4042020 TI - Renal extraction of glutamine from plasma and whole blood: studies in dogs and rats. AB - The change in plasma and blood cell pools of L-glutamine during a single pass through the kidney was studied in dogs and rats. It was shown that the glutamine content of blood cells does not change following one passage through the renal vascular bed in normal or acidotic dogs. Furthermore, an infusion of L-glutamine elevating by 10-fold the plasma concentration of this amino acid only minimally changed the blood cells' glutamine content. Therefore within the time frame of acute experiments, the dog blood cells can be assumed to be impermeable to glutamine in vivo. Accordingly, renal glutamine extraction can be measured using either whole blood or plasma arteriovenous difference in this species. However, the latter value is larger and therefore can be measured more accurately. In normal rats, no net renal glutamine extraction is measured. In contrast, a considerable renal glutamine uptake occurs in acidotic rats, 23% of the extracted glutamine coming from the blood cell pool. A load of glutamine in vivo significantly elevates both the plasma and the blood cell concentration. It is concluded (i) that the renal extraction of glutamine is best estimated using plasma arteriovenous difference in the dog, especially when the renal extraction is small; (ii) that whole blood measurements should be obtained in the rat. PMID- 4042022 TI - Acetylcholine supersensitivity in the rat heart produced by neonatal sympathectomy. AB - Effects of neonatal sympathectomy with antiserum to nerve growth factor or 6 hydroxydopamine on the acetylcholine sensitivity of the rat left atria were investigated. Sensitivities to acetylcholine of atria from immunologically and chemically sympathectomized rats were much higher than that of control at 4 weeks of age. These results suggest possible involvement of the sympathetic nervous system in regulation of cardiac cholinergic sensitivity. PMID- 4042023 TI - Medicine and journalism. PMID- 4042024 TI - Searching for a scientific writing style. PMID- 4042025 TI - Gluten in pills. PMID- 4042026 TI - [Cost of drugs for whiplash caused by traffic accidents]. PMID- 4042027 TI - Evaluation of sponging to reduce body temperature. PMID- 4042028 TI - Preventive care in family practice. PMID- 4042029 TI - Diuretic-induced hypokalemia in hypertension. PMID- 4042030 TI - Absenteeism among hospital staff during influenza epidemic. PMID- 4042031 TI - Faith in healing. PMID- 4042033 TI - Generic drug names: deliberate mouthful? PMID- 4042032 TI - Sexual medicine. PMID- 4042034 TI - Occult blood screening of Canadians: wise or unwise? PMID- 4042035 TI - Factors influencing early diagnosis of cancer of the oral cavity. AB - Factors associated with stage at time of diagnosis and with interval between recognition of the first symptom and histologic diagnosis were assessed in a consecutive series of patients with primary epithelial tumours of the oral cavity. Of the 160 patients 55% had stage I or II disease. The proportion was significantly higher among patients with a high socioeconomic status, those with low levels of alcohol consumption and those who regularly received dental care. The interval between recognition of the first symptom and diagnosis was not significantly related to these factors, but it was shorter for the men. These relations were specific to the patients with cancer of the oral cavity, not being seen in those with other head and neck tumours. Dental practitioners are an important source of early diagnosis of oral cavity cancers. The impact of the disease might thus be lessened by more regular dental care. PMID- 4042037 TI - Erythema multiforme major following use of diclofenac. PMID- 4042036 TI - Sporadic postinfectious neuromyasthenia. AB - Outbreaks of epidemic neuromyasthenia have occurred throughout the world for many years, but sporadic cases have only recently been recognized. Fifty consecutive previously well patients with prolonged and excessive fatigue after an apparent acute infection were investigated. Most were well educated, active, unmarried women aged 30 to 40 years. The precipitating infection had many clinical presentations. The chronic phase of the illness was characterized by a fairly common set of symptoms. Physical examination and laboratory testing generally gave normal results. Of the 50 patients 16 were found to be infected with Epstein Barr virus, 7 with other viruses, 4 with parasites and 2 with Mycoplasma pneumoniae. The causative agent was not known in 22 cases. The mean duration of the illness was 27.6 months, and the mean proportion of time lost from work or school was 39%. Drug therapy was not beneficial; supportive therapy was useful. Further investigation is required to determine optimal management of sporadic neuromyasthenia. PMID- 4042039 TI - Statement on influenza vaccination for the 1985-86 season. PMID- 4042038 TI - Endometritis due to Mycobacterium tuberculosis. PMID- 4042040 TI - Influenza in Canada, 1984-85. PMID- 4042041 TI - Can medical paternalism be justified? PMID- 4042042 TI - The rising popularity of cocaine: how serious a problem? PMID- 4042043 TI - Distributing physicians. PMID- 4042044 TI - Building a table: 1. PMID- 4042045 TI - CMA's policy summaries. PMID- 4042046 TI - The Eastman prescription: a dispensable package. PMID- 4042047 TI - The plow in front of the bull. PMID- 4042049 TI - Nomifensine-induced dyskinesia. PMID- 4042048 TI - Age at death: physicians and ministers of religion. PMID- 4042050 TI - The hypocrisy of abortion. PMID- 4042051 TI - Treatment for primary varicose veins. PMID- 4042052 TI - Sleep disorders in hospital. PMID- 4042053 TI - Smoking and health. PMID- 4042054 TI - Passive smoking has no place in the workplace. PMID- 4042055 TI - Amoxicillin-clavulanate (Clavulin). Infectious Diseases and Immunization Committee, Canadian Paediatric Society. PMID- 4042056 TI - Pediculosis capitis (head lice). Infectious Diseases and Immunization Committee, Canadian Paediatric Society. PMID- 4042057 TI - A syndromic approach to common parasitic diseases. AB - Standard textbooks discuss parasitic disease according to specific organisms. In contrast, patients with parasitic infections present to physicians with a variety of clinical manifestations that may involve any of several organ systems and that often mimic nonparasitic diseases. A syndromic approach to the clinical situation may help the physician in considering the most important parasitic agents. Many parasitic infections can be acquired in temperate climates. While often considered tropical or exotic, other parasitic diseases are now seen more frequently in developed countries because of immigration and increased world travel. In this review the clinical syndromes associated with common parasitic diseases in North America are discussed, with an emphasis on risk factors and diagnosis of specific infections. PMID- 4042058 TI - New approaches to measuring nausea. AB - Valid measures of nausea are needed to evaluate the various treatments used to counter the nausea produced by chemotherapy. The overall nausea intensity (ONI) produced by 17 chemotherapy drugs was estimated by 17 physicians and 8 nurses, and 25 patients undergoing chemotherapy described the subjective qualities and ONI of their nausea on a modified form of the McGill Pain Questionnaire. The scores for the affective and miscellaneous categories of words in the questionnaire were found to correlate significantly with the physicians' and nurses' ONI estimates. The results formed the basis for the Nausea Questionnaire, which provided three indices of nausea: a nausea rating index (NRI), ONI and intensity of nausea according to a visual analogue scale (VAS). All three indices correlated significantly with the physicians' and nurses' ONI estimates and were significantly intercorrelated. All three also provided significant differences when the scores of patients who had received cisplatin or 5-fluorouracil were compared. The results indicate that the Nausea Questionnaire provides three valid indices of the subjective experience of nausea. PMID- 4042059 TI - Relative costs of specialist services in a family practice population. AB - The frequency and cost of referrals to specialists in March 1984 for 8980 rostered patients attending a family practice clinic located in a teaching hospital were analysed. The patients made 1891 visits to specialists. In all age groups and for all specialties female patients were more likely to be seen. The total direct provider costs were higher for female patients than for male patients. However, costs per patient seen were higher for male patients, except for psychiatry and medicine. Visits to surgeons had the highest total cost, while visits to psychiatrists had the highest cost per patient seen. Of the direct provider costs 61% was for specialist services. The family physician, in the "gatekeeper" role, has an opportunity to control some of the costs of the health care system by ensuring that the best and most efficient use is made of the referral network. PMID- 4042060 TI - Disseminated histoplasmosis in a nonendemic area. PMID- 4042061 TI - Cutaneous abscess due to Nocardia after "alternative" therapy for lymphoma. PMID- 4042062 TI - Case of tetanus in British Columbia. PMID- 4042063 TI - The debate: animals in laboratories. PMID- 4042064 TI - From sneakers to vinyl shoes (animal activists). PMID- 4042065 TI - Hypnosis: with legitimacy comes questions. PMID- 4042066 TI - Smoking: it's time we stopped moralizing about a health issue. PMID- 4042067 TI - Ethics and editors: when should unethical research be published? PMID- 4042068 TI - Drinking and driving. PMID- 4042070 TI - Mitomycin in metastatic breast cancer refractory to hormonal and combination chemotherapy. AB - Forty-three patients with evaluable metastatic breast cancer refractory to hormonal agents and extensive combination chemotherapy including doxorubicin were treated with mitomycin, 20 mg/m2 intravenously every 6 weeks. There were five partial responses (12%) and three minor responses (7%), with a mean time to progression of 5 months and 3.5 months, respectively. Thrombocytopenia was the major dose-limiting toxicity, and myelosuppression was cumulative. Cardiac dysfunction was observed in 12% of patients. Mitomycin had some antitumor activity in this group of metastatic breast cancer patients refractory to extensive combination chemotherapy including doxorubicin. PMID- 4042069 TI - DNA damage and cell killing. Cause and effect? AB - The evidence supporting a cause and effect relationship between DNA damage and cell killing is examined in the light of what is currently known about the organization and replication of genomic DNA in eukaryotic cells and the radio energetics of DNA breakage. A large disparity is identified between characteristic doses for cell killing and for the production of DNA lesions (i.e., single- or double-strand breaks). In contrast, the sensitive phase of the inhibition of DNA synthesis has a dependence on dose quantitatively similar to that of cell killing. A model is developed in which single- and double-strand breaks are associated with the inhibition of replicon initiation, whereas only double-strand breaks are primarily responsible for strand elongation. Furthermore, the model points to the replisome and the region of replicated DNA just downstream from the fork as the locus of radiation action. PMID- 4042071 TI - A phase I and pharmacology study of continuous-infusion low-dose methotrexate administration. AB - Continuous intravenous infusion of methotrexate (MTX) was evaluated in a Phase I study designed to establish the optimal dose rate to provide a minimum of 28 days of constant 24-hour drug exposure. Twenty-six courses were administered to 21 patients at dose rates of 0.75 mg/M2/day to 3 mg/M2/day. Dose-limiting toxicity was predominantly stomatitis at the highest dose rates. Thrombocytopenia (platelet count less than 100,000) without leukopenia developed in 8 of 26 courses at the lower dose rates, with or without stomatitis, and was rapidly reversible. Serial blood levels revealed detectable serum MTX concentrations at all dose rates delivered with mean MTX concentrations varying from 12.8 nM at 0.75 mg/M2/day to 140 nM at 2.5 mg/M2/day. Total-body clearance of MTX approximated renal creatinine clearance. The recommended dose rate for continuous infusion of methotrexate is 0.75 mg/M2/day for 28 days, and for shorter durations (less than or equal to 14 days), the optimal dose rate is 1.5 mg/M2/day. The continuous-infusion schedule for MTX, therefore, results in a substantial decrease in the delivered dose compared with that achieved with a bolus schedule. PMID- 4042072 TI - 5-Fluorouracil and methotrexate administered simultaneously as a continuous infusion. A phase I study. AB - Infusion delivery systems have been evaluated for administration of many individual chemotherapeutic agents including 5-fluorouracil (5-FU) and methotrexate (MTX). This study combined the two drugs as an admixture, and in a Phase I trial design established a useful dose schedule for each of the component drugs. 5-FU at a fixed dose rate of 300 mg/M2/day was delivered with methotrexate (MTX) at four different dose rates (0.75, 1.0, 1.5, or 2.0 mg/M2/day, respectively). The drug solution was delivered via a subclavian venous access with a portable infusion pump in an ambulatory setting. Twenty-nine patients received a total of 38 courses of the two-drug infusion: 21 courses were delivered with the two agents admixed constantly throughout treatment (Schedule A) and 17 were administered the treatment with 5-FU delivered continuously and MTX added to the 5-FU for alternate 14-day cycles (Schedule B). For the former schedule, dose-rate-limiting toxicity was related to MTX and included stomatitis developing at days 8 to 14 (median, day 8) with the higher dose rates (1.5-2.0 mg/M2/day) and thrombocytopenia developing at days 11 to 56 (median, day 14) at the lowest dose rates (1.0 mg/M2/day). For Schedule B, dose-rate-limiting toxicity was similarly due to the MTX with thrombocytopenia and/or chemical hepatitis developing in six of seven courses of MTX at 1.0 mg/M2/day and in five of ten courses delivered at 0.75 mg/M2/day. On Schedule B the MTX-associated toxicities were reversed when the MTX administration was interrupted and in the face of continued 5-FU infusion. A reasonable dose rate and schedule for continuous infusion of 5-FU combined with MTX is: 5-FU 300 mg/M2/day X 28 days and MTX 0.75 mg/M2/day for days 1 to 14, with cycles administered consecutively each 28 days. PMID- 4042073 TI - Transthoracic fine-needle aspiration. Experience in a cancer center. AB - The authors summarize 5 years' experience with transthoracic fine-needle aspiration (TFNA) in 180 patients. Aspirated tumors tended to be large and peripheral. A large pneumothorax was seen after 4.3% of aspirations, and various minor complications followed another 23.3%. Emphysema was a significant risk factor for complications. Follow-up confirmed 151 cancers, with a wide variety of origins and histologic types. In the diagnosis of cancer, TFNA cytology had a specificity of 100% and a sensitivity of 82%. Positive TFNA findings usually provided the earliest microscopic diagnosis of cancer or of cancer stage. PMID- 4042074 TI - Adenocarcinoma of the esophagus and gastroesophageal junction. Prognostic factors and results of therapy. AB - Adenocarcinomas of the esophagus and gastroesophageal junction (AE and GE) are uncommon neoplasms with a poor prognosis. AE or GE are usually analyzed as part of the larger group of carcinomas in patients with either epidermoid carcinoma of the esophagus or with gastric cancer. The prognostic variables and outcome of therapy for patients with AE and GE alone have not been well described. The records of 131 patients treated at Memorial Hospital during the period 1978 to 1982 were reviewed. The majority underwent surgery as their primary therapy. Clinical staging was found to be highly inaccurate, with almost all patients having Stage III disease at surgery. Operative mortality was 7.1%. Adjuvant chemotherapy did not appear to influence survival. Treatment of advanced disease with either conventional or investigational agents yielded modest objective response rates. Prognostic variables for those presenting with locoregional disease who were candidates for potentially curative surgery were analyzed. Only the presence or absence of weight loss and location of the primary tumor (AE versus GE) were significant variables. A model for predicting survival was employed. PMID- 4042075 TI - Gynecomastia in testicular cancer patients. Prognostic and therapeutic implications. AB - Eighty-one patients with advanced testicular cancer were evaluated for gynecomastia or severe breast tenderness at diagnosis and after platinum-based chemotherapy. The prognostic significance of gynecomastia in these two settings was explored. At presentation, 10% (8 patients) had gynecomastia or breast tenderness and elevated HCG levels. The likelihood of gynecomastia was greater with increasing HCG level (P = 0.002). However, gynecomastia at presentation was a more powerful independent discriminant of poor survival than the initial HCG level by multivariate analysis (P = 0.004). Fifteen percent (12 patients) developed transient gynecomastia after chemotherapy not attributable to other known causes. HCG levels were normal. Endocrine evaluation typically revealed elevated FSH, LH, and estradiol/testosterone ratios. This may have reflected damage to testicular germinal epithelium. All 12 patients are alive without disease in contrast to the 8 patients who had gynecomastia at diagnosis. Therapy decisions should therefore be based on the time of onset of gynecomastia and in the context of appropriate clinical markers and evaluation. PMID- 4042077 TI - The human B-cell lineage cell line ARH-77. PMID- 4042076 TI - Burkitt's lymphoma in the Middle East. A study of 34 cases. AB - The clinical features of 34 patients with Burkitt's lymphoma diagnosed at the American University Medical Center (AUMC) are described. Ages ranged between 3 and 20 years (median, 7 years). Seventy-three percent of the patients were younger than 8 years. Three cases occurred among siblings. The primary site of disease at presentation was the abdomen, 23 patients; jaw, 6; jaw and abdomen, 2; Waldeyer's ring, 2; and mediastinum, 1. Of those who had abdominal disease, the involvement was diffuse and extensive in abdomen and pelvis in 9, apparently confined to the ileocecal region in 5, mesenteric nodes and small intestine in 5, large intestine in 1, and ovary in 3. One patient presented with paraplegia. The bone marrow was studied in 19 patients; it was positive in 5 and suspicious in 2. None had frank leukemia. CSF was studied in 4 patients at presentation and was negative. Eight patients developed meningeal lymphoma during the course of the disease. Liver involvement was documented in 3 patients. Peripheral lymphadenopathy was observed at presentation in 11 patients (9, neck; 2, inguinal + axillary). In contrast to African Burkitt's, the majority of our patients presented with abdominal disease, and in contrast to the American form, our patients were younger with a median age similar to that of African Burkitt's. Thirty percent of the patients had jaw tumor at presentation--a figure intermediate between the African and the American Burkitt's. PMID- 4042078 TI - Effects of a new benzodiazepine derivative, ethyl loflazepate (CM6912), on the arousal level of normal humans assessed by the averaged photopalpebral reflex. AB - The effects of a new benzodiazepine derivative, ethyl loflazepate (CM6912), on the arousal level of normal male human subjects were investigated by use of the averaged photopalpebral reflex (PPR), the latency of which is sensitively prolonged with the lowering of the arousal level. Four doses of ethyl loflazepate, i.e., 2 mg, 4 mg, 6 mg, and 8 mg, and a placebo were administered to each subject 30 min after lunch according to a double-blind, crossover design. Ethyl loflazepate prolonged both latencies of PPR in a dose-dependent manner. The dose-response curves for both latencies, derived from the maximum prolongation, showed a definite and linear dose-response relationship. The drug action occurred within 1 h, peaked at 2.5-3 h, and continued slightly even 4 h after medication. In the subjective assessments, vagueness of thought, sleepiness, and weakness were only slightly observed. These results suggest that ethyl loflazepate could be a potent hypnotic and/or anxiolytic which possesses a relatively rapid onset of action with moderate duration and has no severe side effects. PMID- 4042079 TI - Clinical and subclinical thiamine deficiency in clinical practice. AB - Six patients with gross thiamine deficiency found during normal psychiatric practice in England are described. Two surveys of newly admitted psychiatric patients are recounted. A major degree of biochemical deficiency, with or without minimal clinical manifestations, was found. Only three (1%) of 326 patients surveyed had gross clinical deficiency. It is thought that severe thiamine deficiency, though rare in the Western countries, has not been eradicated. Deficiency may cause psychiatric conditions like Wernicke's encephalopathy or may be a secondary feature in mental illness due to anorexia, in reduced food intake, and in poor nutrition. The importance of being aware of the possibility for correct diagnosis is emphasised. PMID- 4042080 TI - Baclofen-induced memory impairment. PMID- 4042081 TI - Nomifensine in advanced parkinsonism. PMID- 4042082 TI - Transient global amnesia induced by lorazepam. PMID- 4042083 TI - Symposium on methodology and quality assurance in cancer clinical trials. Washington, DC, October 24-26, 1984. PMID- 4042084 TI - Response surface methodology and the design of clinical trials for the evaluation of cancer chemotherapy. PMID- 4042085 TI - Factorial designs for randomized clinical trials. PMID- 4042086 TI - Tree-structured survival analysis. AB - In this note, tree-structured recursive partitioning schemes for classification, probability class estimation, and regression are adapted to cover censored survival analysis. The only assumptions required are those which guarantee identifiability of conditional distributions of lifetime given covariates. Thus, the techniques are applicable to more general situations than are those of the famous semi-parametric model of Cox. PMID- 4042087 TI - Regression models for prognostic prediction: advantages, problems, and suggested solutions. AB - Multiple regression models have wide applicability in predicting the outcome of patients with a variety of diseases. However, many researchers are using such models without validating the necessary assumptions. All too frequently, researchers also "overfit" the data by developing models using too many predictor variables and insufficient sample sizes. Models developed in this way are unlikely to stand the test of validation on a separate patient sample. Without attempting such a validation, the researcher remains unaware that overfitting has occurred. When the ratio of the number of patients suffering endpoints to the number of potential predictors is small (say less than 10), data reduction methods are available that can greatly improve the performance of regression models. Regression models can make more accurate predictions than other methods such as stratification and recursive partitioning, when model assumptions are thoroughly examined; steps are taken (ie, choosing another model or transforming the data) when assumptions are violated; and the method of model formulation does not result in overfitting the data. PMID- 4042088 TI - Size of phase III cancer clinical trials. PMID- 4042090 TI - Policies for interim analysis and interim reporting of results. AB - The key ethical issues involved in developing policies for interim reports and interim analyses are considered. Then the twin topics of the appropriate contents of interim reports and the components of an appropriate interim analysis are discussed. Finally, suggested policies are offered. PMID- 4042089 TI - The doctor's dilemma: physician participation in randomized clinical trials. PMID- 4042091 TI - Eligibility exclusions, losses to follow-up, removal of randomized patients, and uncounted events in cancer clinical trials. AB - This paper reviews the potential impact of eligibility exclusions, losses to follow-up, removal of randomized patients from the analyzed data, and failure to count all observed events on the interpretation of cancer clinical trials. The pragmatic and explanatory approaches to these problems are presented, and it is argued that most clinical trials yield data that are suitable for answering pragmatic questions. Thus, the pragmatic approach to these problems is stressed. PMID- 4042092 TI - Influence of measurement error on response rates. PMID- 4042093 TI - An efficient design for phase III studies of combination chemotherapies. PMID- 4042094 TI - Food and Drug Administration requirements for approval of new anticancer drugs. AB - For approval of new drugs, the law requires a minimum of two independent well controlled studies for each indication. The preferred study design is prospective, randomized, and comparative. The use of historical controls, while sometimes acceptable, must be justified. A favorable effect on survival and/or quality of life is generally required for approval. The study of cancer drugs in combination presents problems which are discussed. Drug firms are strongly urged to discuss the protocols with the Food and Drug Administration prior to initiating phase III comparative studies to be used for approval of the drug. PMID- 4042095 TI - Applicability of phase I trial results in the design of phase II and III biological response modifier trials. PMID- 4042096 TI - Site visit monitoring program of the clinical cooperative groups: results of the first 3 years. PMID- 4042097 TI - Quality assurance in a cooperative group. AB - Quality control in a large cooperative group involves a number of different levels of checking which can be divided into three main sections: quality control in data management, quality control in special areas, and the verification that events on paper reflect real events in the clinic. Quality control in special areas is the province of those using various techniques and disciplines and it will not be discussed in this overview, since others will cover the monitoring of radiation therapy, standardization of biochemical tests, and pathology review. PMID- 4042098 TI - Clinical quality assurance in the pharmaceutical industry. PMID- 4042099 TI - Quality assurance of radiotherapy in clinical trials. PMID- 4042100 TI - Pathology quality control in the cooperative clinical cancer trial programs. AB - Pathology quality control is an essential part of clinical cancer research. However, pathology review for every study may not be practical; therefore, review in most cooperative groups will be performed only for selected protocols. The selection process should include those neoplasms with an expected diagnostic error rate which would affect the outcome of the study. Unfortunately, complete information about the diagnostic error rate for various neoplasms is not available at the present time; however, enough information is available from the pathology review experiences of the last decade to draw some general guidelines. All lymphomas should have pathology quality control review as should rare or difficult-to-diagnose neoplasms. Early cancer is likely to cause diagnostic disagreement, so protocols designed to evaluate various treatment options for such neoplasms should include pathology review. The diagnostic error rate for far advanced carcinoma, most adenocarcinomas of the gastrointestinal tract and squamous cell carcinomas, is so low that routine pathologic quality control review is not cost-effective, in our opinion. However, pathology review may be pathology research, and in this circumstance, pathology review will be carried out to answer research questions. Whether or not pathology quality control review is needed should be determined at the time of development of each protocol. PMID- 4042101 TI - Hospital ethics committees: a pediatric neurosurgical perspective. AB - The Pediatric Neurosurgical Section of the American Association of Neurological Surgeons was polled regarding the status of hospital ethics committees. Twenty four committees were identified in 74 pediatric neurosurgical centers in the United States. (Thirteen of these were formed between October 1983 and February 1984.) In addition, 21 are in the planning stages. Physicians predominate, with nurses, hospital administrators, the clergy, social workers, attorneys and lay persons usually represented. Functions include review of ethical and patient care decisions and providing counsel and support primarily to physicians and nurses. Rarely do committees make policy, determine prognosis or make final decisions regarding life-support systems. Approximately one case per year is reviewed. Committee formation frequently appears to be a crisis response to highly publicized pediatric cases and recent positions of the Department of Health and Human Services. Their purpose, construct, function and utilization raise serious questions as to their usefulness and necessity. PMID- 4042102 TI - Transplacental induction of myeloschisis associated with hindbrain crowding and other malformations in the central nervous system in Long-Evans rats. AB - Nine groups of 66 pregnant rats, grouped by gestation days 11 to 19, were subjected to a single, intragastric administration of ethylenethiourea (ETU). Cesarean section was performed on gestation day 20. No dam died following the ETU treatment, although a mortality as high as 21.2% was noted among the fetuses in this group; the remaining live fetuses were found to suffer from a high incidence of myeloschisis associated with hindbrain crowding. Exencephaly and abnormally enlarged head with occipital bossing due to the herniation of the mesencephalic tectum, with and without dilation of the mesencephalic and 4th ventricles, were induced among the fetuses of the dams given ETU at gestation days 12 and 13. Various degrees of hydranencephaly and dysplastic hydrocephalus were found among the fetuses of dams treated by ETU from gestation days 14 to 18. From the histological features of these malformations of the central nervous system (CNS), a possible mechanism in the induction of myeloschisis with hindbrain crowding induced by ETU is discussed, and compared with the previously reported similar malformations induced by trypan blue. PMID- 4042103 TI - Shunt placement and myelomeningocele repair: simultaneous vs sequential shunting. Review of 12 cases. AB - The optimal management of patients with myelomeningocele and hydrocephalus is facilitated by a constant review of the patients with the aid of the sonogram and CT scan. Six infants treated with simultaneous shunt placement and myelomeningocele repair were compared with six other neonates treated with conventional sequential myelomeningocele repairs requiring a second separate procedure for shunt placement. Infants operated upon simultaneously experienced no increase in morbidity or mortality and appeared to benefit substantially. PMID- 4042104 TI - In vitro evaluation of CSF shunt function by radionuclides. AB - An in vitro study of clearance of a radiolabeled marker was conducted on nine commonly used shunting devices. Clearance of 0.5 ml of 113mIn-diethylenetriamine pentaacetic acid (DTPA) injected into the chamber, by water infused through the system at constant rate (0.034-0.46 ml/min), was measured by monitoring activity over the chamber and accumulating counts at 5-s intervals on a multichannel analyzer. Each flow rate was triplicated, and a graph of log value of counts versus time made. A mean t1/2 was computed for each flow rate and a new graph constructed. A best-fit curve constructed for the graph of each shunt system allows determination of flow rate for a known half time of isotope clearance. PMID- 4042105 TI - Severe head injury in children: early prognosis and outcome. AB - The outcome is reported in 62 children with severe head injuries following a road traffic accident. All patients were comatose for at least 6 h; all patients were graded using the Glasgow Coma Score (GCS) or the Children Coma Score (CCS). Fifty four patients were comatose immediately after injury, 8 after a lucid interval. Thirty patients had isolated head injuries and 32 had associated injuries, either long bone fractures or rupture of an abdominal organ. Additional information concerning main brainstem reflexes, posture and respiration was included in the study. The overall mortality was 32%. The goal of the study was to identify those clinical features available soon after injury which are important indicators of treatment and outcome. PMID- 4042106 TI - Short-term culture of pediatric brain tumors. AB - Three short-term culture systems were applied to ten pediatric brain tumors and two samples each of normal child's brain and fetal brain. Growth in monolayer occurred in nine of the ten tumors but normal child's brain also produced cellular growth in these conditions. Six of nine tumors tested also formed colonies in suspension in semisolid or liquid conditions which did not permit the growth of normal glial cells. Astrocytomas and medulloblastomas have distinctive growth patterns both in monolayer and in suspension culture. Fetal brain from midtrimester abortions contained cells which, like tumor, formed colonies in suspension. The semisolid culture system was then used to test the sensitivity of brain tumor stem cells to drugs and radiation in vitro. Survival curves representative of our experience with the medulloblastomas and astrocytomas are presented. It is concluded that the system may have value in screening new agents for activity against children's brain tumors but because of the relative rarity of these diseases, a cooperative effort would be required to produce useful results. PMID- 4042107 TI - Intracranial sarcoma in childhood. AB - Three cases of intracranial sarcomas in children are presented. The children were 1 month, 8 months and 7.5 years old. In two cases the tumor was in the cerebral hemisphere and in one case (the 7.5-year-old child) in the cerebellum. The histopathological diagnosis was undifferentiated sarcoma and spindle cell sarcoma in the cases with tumor in the cerebral hemisphere and arachnoidal sarcoma of the cerebellum. There was one postoperative death. The two children subjected to postoperative X-ray therapy and cytostatic therapy survived 1.75 years and 7 months, respectively. PMID- 4042108 TI - The application of evoked potentials in the diagnosis and follow-up of children with intracranial tumors. AB - Somatosensory and brainstem auditory evoked potentials (SSEPs and BAEPs) provide sensitive measures of the central conduction functions of the auditory and somatosensory input systems at different levels of the central nervous system. The contribution of SSEPs and BAEPs in the primary diagnosis and follow-up of 26 children with infra- and supratentorial tumors were reviewed. The SSEPs, especially the specific complex, showed a latency increase in patients with supratentorial and brainstem mass lesions involving directly or distantly the somatosensory tracts. The BAEPs were sensitive for supratentorial pressure effects and for local and distant posterior fossa tumor effects. In the follow-up of children, evoked potentials offer a good method of detecting tumor recurrence, whereas neuroradiological procedures may be obscured by surgical or radiation artifacts. PMID- 4042109 TI - A cranial nail for fetal shunting. AB - A small number of human fetal hydrocephalics have been treated by ventriculoamniotic shunts of silastic tubing. The Colorado device appears to be the one most commonly used. The original experimental device tested on a primate model resembled a hollow shingle nail. This was designed by Michedja and Hodgen, contained a spring valve, measured approximately 32 X 4 mm and was placed by hysterotomy. An attractive feature of this design was its fixation by impaction in the skull, preventing displacement by fetal activity, a reported disadvantage with the silastic devices. To our knowledge, no one has used this nail-like design and tailored it to transuterine percutaneous placement in a human case. PMID- 4042110 TI - A rapid mass-spectrometric procedure for probing the non-reducing structures of lactosaminoglycan-containing glycoconjugates. PMID- 4042111 TI - Experimental modification of N-linked sugars of membrane proteins in a lymphoma cell line affects the binding of soybean agglutinin but not of several other lectins. PMID- 4042112 TI - A convenient method for methylation of glycoprotein glycans in small amounts by using lithium methylsulfinyl carbanion. AB - Treatment of dimethyl sulfoxide with butyllithium leads to rapid formation of lithium methylsulfinyl carbanion. The reaction products tend to be significantly freer from impurities when lithium methylsulfinyl carbanion is used rather than sodium or potassium methylsulfinyl carbanion. This reagent gives less background in g.l.c. and thus may be used to methylate micro-quantities of glycoprotein glycans (down to 10 micrograms) without the necessity of identifying methyl ethers by mass spectrometry. PMID- 4042113 TI - Mechanism of liposoluble drugs and general anaesthetic's membrane action: action of difluorodichloromethane (FC 12) on different types of cardiac fibres isolated from sheep hearts. AB - The effect of difluorodichloromethane (FC 12), a chemically stable aerosol propellant which has long been considered innocuous, on several types of cardiac fibres isolated from sheep hearts after preparation in a nutritive solution was studied. Modifications in resistance and transmembrane potentials suggested a mechanism of FC 12 action. Physical constraint on membrane structures produced by high FC 12 concentrations from simple dissolution in the internal lipid layer explain modifications in cardiac membrane properties. Variable effects of FC 12 with localisation and time on automatism, excitability, and conduction in various types of cardiac tissue agreed with earlier observations of the depressive and arrhythmia effect of this gas on isolated and in situ hearts. PMID- 4042114 TI - Effect of clonidine and naloxone on the pressor response during contraction of cat hind-limb muscles. AB - The possible involvement of an adrenergic-endorphin system in the mediation of the pressor response to isometric muscular contraction was studied in cats. Fatiguing contractions of the gastrocnemius and plantaris muscles caused an increase in the mean arterial blood pressure by 35 to 70 mmHg. Intravenous infusion (30 micrograms X kg-1) as well as intracisternal injection (2.5 micrograms) of clonidine-HCl eliminated the pressor response to muscular contraction. In both sets of experiments, the mean blood pressure remained at the resting level throughout the duration of the isometric contraction. Injection of naloxone (0.5 mumol X litre-1) into the cisterna magna did not alter the resting blood pressure and did not affect the rise in mean arterial pressure during muscle contractions. Intracisternal injection of naloxone (0.5 mumol X litre-1) prior to an intracisternal injection of clonidine (2.5 micrograms) did not alter the resting blood pressure but effectively antagonised the anti-pressor effects of clonidine during fatiguing isometric contractions. These data may indicate that activation of muscle "ergoreceptor" afferents (group III and IV fibres) during muscular contraction may cause an increase in the arterial blood pressure by interfering with an inhibitory adrenergic-endorphinergic pathway in the brainstem. PMID- 4042116 TI - Subendocardial and subepicardial segmental function changes in the dog heart due to gradual coronary flow reduction by an acutely developing thrombus. AB - Regional myocardial dynamics were assessed during continuous, gradual coronary flow reductions caused by spontaneous thrombus formation in the stenosed left circumflex coronary artery of eight open chest dogs. Contractile changes in the subendocardial and subepicardial layers were measured by ultrasonic crystal techniques. Segment length shortening was continuously measured as coronary flow reductions occurred. Contractile dysfunction in the subendocardium preceded that in the subepicardium. At lowest flow levels the subendocardial function degenerated to severe holosystolic bulging whereas some systolic shortening was maintained in the subepicardium. Exponential equations derived to express changes in end diastolic segment length and end systolic length as a function of coronary blood flow for both subendocardium and subepicardium indicated that increases in end systolic length were a more sensitive index of ischaemia than increases in end diastolic length for both the subendocardium and subepicardium during coronary flow reduction. Comparison of exponential curves of end diastolic segment length vs coronary blood flow in subendocardium and subepicardium showed a small but significant difference (p less than 0.02). Comparison of exponential curves of end systolic length vs coronary blood flow in subendocardium and subepicardium showed a large difference in changes at end systole occurring between subendocardium and subepicardium (p less than 0.001). Active contraction of the subepicardium may serve to limit the extent of paradoxical systolic segment lengthening in the underlying ischaemic myocardium and thus help to preserve ventricular function during acute gradual coronary flow limitation. PMID- 4042115 TI - The beneficial effect of amrinone on acute drug-induced heart failure in the anaesthetised dog. AB - Amrinone, a positive inotropic-vasodilator agent, was administered to anaesthetised dogs in an attempt to reverse heart failure induced by drugs possessing negative inotropic properties. Propranolol, a beta-adrenergic blocker; verapamil, a calcium slow-channel blocker procainamide, a type 1 antiarrhythmic agent; or sodium pentobarbital, a barbituate; administered as a bolus injection and/or infusion, produced a sustained depression in canine cardiac function. Cardiac depression was characterised by a greater than 40% reduction in cardiac contractile force (CF) and maximum left ventricular pressure development (LV dp/dtmax), a 30 to 50% reduction in cardiac output (CO) and concomitant increases in mean central venous or mean right atrial blood pressures (CVP, RAP, respectively). Amrinone, when administered intravenously as a bolus injection (1 or 3 mg X kg-1) plus an infusion (0.03 or 0.1 mg X kg-1 X min-1) reversed the depression in cardiac function by increasing CF, CO and LV dp/dtmax and decreasing preload CVP or RAP in all four drug-induced failure models. Due to the vasodilator properties of amrinone, afterload, total peripheral resistance (TPR), was reduced in verapamil and procainamide failures as well as in propranolol failure, the only model where TPR increases. In another model of heart failure, in which ouabain-induced arrhythmias preceded procainamide toxicity, amrinone was also an effective cardiotonic agent. Ouabain's inotropic effect was studied in propranolol-induced heart failure. Although an increase in LV dp/dtmax and a decrease in CVP were noted, ouabain (40 micrograms X kg-1 iv) increased TPR and had little effect on the depression in CF and CO. Drug-induced models of heart failure were useful pharmacological tools for evaluating the cardiotonic agent's ability to overcome severe cardiac depression. In propranolol-, verapamil-, procainamide-, and pentobarbital-induced cardiac toxicity, amrinone could be of therapeutic value. PMID- 4042118 TI - Abstracts of symposium organised by the Cardiac Muscle Research Group. Bath, 16 April 1985. PMID- 4042117 TI - Calf muscle adaptation to peripheral vascular disease. AB - 130 muscle biopsies were taken from the gastrocnemius of 82 patients with different degrees of peripheral vascular disease (PVD) and 19 normal controls for histochemical analysis, and 30 patients and 7 controls for biochemical analysis of "aerobic" and "anaerobic" enzymes. The results showed that the gastrocnemius of patients with PVD did not adapt by increasing its "aerobic" potential as previously suggested. Histochemical studies showed that the cross-sectional area of both Type 1 and Type 2 muscle fibres became smaller than those from age matched controls in the presence of PVD, and in some cases biopsies from both legs confirmed that this trend was greater in those limbs with increasing evidence of PVD. There is also some evidence to suggest a decrease in absolute capillary numbers per muscle fibre. The biochemical assays confirmed decreased levels of aerobic enzymes with increasing evidence of PVD as judged by ankle systolic pressure, and those patients with intermittent claudication showed some evidence of increased anaerobic enzyme levels in comparison to both the normal controls and those with rest pain. Patients with PVD do not adapt to ischaemia/anoxia by increasing their aerobic capability, but show signs of muscle atrophy probably due to reduced mobility. Training regimes may benefit patients with intermittent claudication by reversing these changes. PMID- 4042119 TI - Inhibition of the baroreceptor heart rate reflex by angiotensin II in normal man. AB - Eight normotensive male subjects were infused with angiotensin II or phenylephrine in a single blind fashion. Measurements were made of blood pressure and pulse interval every 3 min, and blood drawn for plasma catecholamines at the beginning and end of the infusion. Phenylephrine produced a rise in blood pressure which was associated with a bradycardia in all subjects. A statistically significant relationship between blood pressure and pulse interval was observed in all subjects. In contrast, angiotensin II infusion produced an equal pressor response, but the change in pulse interval was statistically significantly less than that seen following phenylephrine infusion. In seven of eight subjects no significant relationship was observed between blood pressure and pulse interval. Plasma noradrenaline levels were similar before each pressor infusion and were unchanged during each infusion. These observations are consistent with central inhibition of the baroreceptor heart rate reflex by angiotensin II in man. PMID- 4042120 TI - Lack of effect of anti-hypertensive treatment with felodipine on cardiovascular structure of young spontaneously hypertensive rats. AB - Felodipine (4(2,3-dichlorophenyl)-1,4-dihydro-2, 6-dimethyl-3-ethoxycarbonyl-5 methoxycarbonyl pyridine)), a selective vasodilating anti-hypertensive drug, was used in the treatment of spontaneously hypertensive rats (SHRs) and age-matched Wistar-Kyoto rats (WKYs) from age 6 to 14 weeks, ie during the time of high blood pressure development in SHRs. The effect of treatment on heart weight and on mesenteric resistance vessels (i.d. ca 170 microns) characteristics was investigated. In a first study, two oral doses of felodipine were added to the diet of SHRs, in concentrations of either 0.5 or 1.5 mg X g-1 rat food. Both treatments lowered mean arterial pressure by about 19% (p less than 0.001). In a second study, the lower dose of felodipine (0.5 mg . g-1 rat food) was therefore used to treat both SHRs and WKYs. Treatment did not interfere with weight or food intake of either SHRs or WKYs but increased average weekly water intake significantly. In neither strain was the pulse rate or, surprisingly, heart/body weight ratio affected by treatment. Furthermore, mesenteric resistance vessel morphology and mechanics were not affected by the blood pressure reduction. The noradrenaline and calcium sensitivity of mesenteric resistance vessels from treated rats was greater (p less than 0.001) than those from control rats. These findings indicate that blood pressure reduction with felodipine does not affect cardiovascular structure in young SHRs. PMID- 4042121 TI - Reversal of strophanthidin negative inotropy by metabolic substrates in cardiac Purkinje fibres. AB - The action of substrates and metabolic inhibitors on strophanthidin inotropy was studied in canine cardiac Purkinje fibres perfused in vitro. Both membrane potentials and contractile force were recorded. The results show that: 1) pyruvate (1 to 10 mmol X litre-1) decreases and then increases contractile force in Tyrode solution or in the presence of a low concentration of strophanthidin without modifying the action potential magnitude or configuration; 2) during the decreasing (but not the increasing) phase of strophanthidin (2 to 5 X 10(-7) mol X litre-1) inotropy, pyruvate increases contractile force; 3) beta hydroxybutyrate has effects similar to those of pyruvate; 4) glucose increases contractile force and more so during the descending phase of strophanthidin inotropy; 5) the positive inotropic effect of pyruvate during declining strophanthidin inotropy is not prevented by glucose-lack and/or by iodoacetate but is markedly reduced in a hypoxic solution; 6) in contrast, glucose under similar conditions has the usual effects in hypoxia but not in the presence of iodoacetate; 7) the combination of hypoxia and glucose-lack leads to a decline in contractile force and to contracture: strophanthidin increases both contractile and resting force whereas O2 and/or glucose relax the contracture; 8) pyruvate has a positive inotropic effect also in the presence of high (greater than 10 mmol X litre-1) calcium. It is concluded that the decline in contractile force during exposure to strophanthidin or high calcium can be reversed by providing suitable substrates and therefore may involve a deficit in the production of high energy phosphates. PMID- 4042122 TI - Verapamil induced increment of oxygen extraction in the arteriosclerotic limb. AB - The acute effect of intravenously administered verapamil (0.08 mg X kg-1 body weight, mean dose 5.1 +/- 0.7 mg) on oxygen exchange and arterial blood flow (measured electromagnetically) of the lower limb was studied during reconstructive arterial surgery in 17 patients with obliterative arterial disease of the lower limbs. Verapamil increased oxygen extraction in the diseased leg by 12% (from a median value of 28.3 to 31.6 ml X litre-1, p less than 0.01) whereas it had no effect on arterial blood flow. The increment of oxygen extraction after drug administration correlated negatively with the walking distance of the patients (r = 0.69, p less than 0.01). Systolic and diastolic blood pressure decreased significantly by 10% and 6%, respectively, whereas heart rate remained unchanged after the administration of verapamil. The results suggest that verapamil might be beneficial in the treatment of patients with intermittent claudication, despite the fact that no vasodilatation was seen after the drug. PMID- 4042124 TI - Isoprenaline-evinced disturbances in action potentials from hearts of young cardiomyopathic hamsters. AB - The electrophysiology of ventricular cells from prenecrotic stage 10 to 14 day old hamsters with hereditary cardiomyopathy (BIO 14.6 strain) was studied with the intent of learning more about the previously documented relationship of stimulation with beta-adrenergic agonist and the sarcolemmal defect contributing to the excessive uptake of calcium by diseased cells. Before catecholamine treatment only slight differences were observed in the configuration of action potentials of myopathics and control random bred hamsters (BIO RB strain). However, isoprenaline in varying concentrations, increased the action potential duration (APD) at 50% and 95% repolarisation levels to a significantly greater extent in myopathics than in controls. Repetition of the dose-response to isoprenaline in the presence of the beta-adrenergic antagonist propranolol (0.1 mumol X litre-1) permitted the calculation of the dissociation equilibrium constant for the antagonist. The similarity of dissociation constants between strains, 0.008 mumol X litre-1 for controls and 0.011 mumol X litre-1 for myopathics, suggests that a difference in interstrain receptor affinities is an unlikely cause of the isoprenaline effect. Rather, the data are more consistent with the hyper-sensitivity resulting from larger numbers of beta-adrenoceptors on sarcolemma of myopathic cells. Also, the increase in APD of myopathics indicates that isoproterenol elicits an imbalance of slow inward calcium and late outward potassium currents. The possible significance of the isoprenaline hyper sensitivity, which is the earliest pathophysiology seen in this disease, to the etiology of cellular calcium overload and degeneration of diseased myocardium remains to be determined. PMID- 4042123 TI - Effect of adenosine deaminase inhibitors on myocardial reactive hyperaemia following brief coronary occlusions. AB - Effect of two agents of adenosine deaminase inhibitor, 8-azaguanine and adenine, on myocardial reactive hyperaemia was tested in the anaesthetised open-chest dog. Reactive hyperaemic flow response of the circumflex coronary artery was observed following 5, 10, 15, 20 and 30 s coronary occlusions before, during and after infusion of 8-azaguanine and adenine, which are known as adenosine deaminase inhibitors. Intracoronary infusion of 8-azaguanine and adenine caused the minimum increase in the baseline coronary flow. Both the nucleic acids shifted the dose response curve of adenosine to the left. 8-azaguanine enhanced volume response of flow at all occlusion intervals tested. The infused dose of adenine also intensified volume response of flow after 5, 15, 20 and 30 s occlusions. Fifteen minutes after termination of the nucleic acid infusions, the reactive hyperaemia returned towards control levels. The results suggest that 8-azaguanine and adenine enhance myocardial reactive hyperaemia possibly by inhibiting adenosine deaminase to degradate myocardial interstitial adenosine to inosine. PMID- 4042125 TI - [Risks in handling antineoplastic chemotherapeutic agents]. PMID- 4042126 TI - [Intermittently studied dynamics of systolic time intervals in intensive care units]. PMID- 4042127 TI - [Soviet research on the regeneration and transplantation of central nervous system tissue]. PMID- 4042128 TI - [Problems in environmental protection in relation to pharmacology]. PMID- 4042129 TI - [The present state of male contraception]. PMID- 4042130 TI - [Basic health care of the aged]. PMID- 4042131 TI - [12 or 16 hours of hemodialysis weekly? A Czechoslovak coil dialyzer, 2 x 6 or 2 x 8 hours weekly]. PMID- 4042132 TI - [Calcium ions, calmodulin and acquired resistance to cytostatic agents]. PMID- 4042133 TI - Selective destruction and regeneration of rat Leydig cells in vivo. A new method for the study of seminiferous tubular-interstitial tissue interaction. AB - The effect of a single i.p. administration of ethane dimethanesulphonate (EDS) upon rat testicular histology was studied by light microscopy and morphometry up to 4 weeks after treatment. One day after injection the interstitial tissue exhibited degenerating Leydig cells, abundant pyknotic interstitial cells, deposition of cellular debris and extensive networks of fibrillar material. Macrophages contained greatly increased numbers of cytoplasmic inclusion bodies. From 3 to 7 days morphometric analysis showed that Leydig cells and cellular debris had disappeared from the interstitial tissue, leaving only macrophages, fibroblasts and lymphatic endothelial tissue. A very small number of new Leydig cells were seen on day 14, often located in peritubular or perivascular positions. Regeneration of foetal-like Leydig cells occurred by 4 weeks, their cytoplasm containing large lipid inclusions and, numerous Leydig cells were often observed closely applied to the walls of the seminiferous tubules. The observations suggest that, after experimental destruction and depletion of Leydig cells, an interstitial precursor cell, as yet unidentified, gives rise to a new Leydig cell population. EDS thus offers a valuable opportunity to study further the interactions between the seminiferous tubules and the interstitial tissue following the destruction and subsequent regeneration of the Leydig cells. PMID- 4042134 TI - Three-day continuous drainage of pancreatic juice in the cortisone-treated conscious rat: analysis of enzyme activities and ultrastructural changes. AB - We have investigated the short-term effects of hydrocortisone (60 mg/kg per day) and placebo on basal and stimulated pancreatic secretion in the conscious rat. Volume and enzyme secretion were determined; fine structural changes were examined simultaneously. The pancreatic and bile ducts were cannulated separately; pancreatic juice was drained via an isolated fistula, and bile was recirculated into the duodenum. The application of hydrocortisone led to an almost complete inhibition of the secretory response of the exocrine pancreas when stimulated with 0.25 U secretin in combination with 5 X 10(-8) g caerulein per h. It strongly affected the secretion rates of volume, protein, lipase, chymotrypsin, trypsin and carboxypeptidase, whereas the secretion rate of alpha amylase continued to show a slight increase after stimulation. After stimulation with secretin and caerulein, the hydrocortisone-treated animals showed a higher density of zymogen granules in the acinar cell and an increase in the number of autophagic vacuoles in comparison to the equally stimulated placebo-treated rats. It is concluded that the short-term inhibition of pancreatic secretion by hydrocortisone occurs largely as a result of an inhibition of cellular enzyme discharge. PMID- 4042136 TI - Potassium concentration in membrane-associated particles in the epiphyseal growth plate. AB - Electron-dense particles with a diameter of 50-200 nm have been observed at the cell membrane of chondrocytes in the zone of the initiation and advance of mineralization, using the dark field STEM mode. Electron-probe x-ray microanalysis and laser microprobe mass analysis indicate that these particles contain predominantly K and Na. They appear only in dry thin sections of shock frozen, freeze-dried embedded tissue and not in sections of water-treated samples; hence they contain water-extractable potassium and sodium. The function of the two elements at these special sites is not yet clear. On the one hand, they might reflect exocytotic processes connected with a Na-K-ATPase; on the other hand, they might exist as a transitory state before being replaced by Ca and phosphate in the mineralizing matrix and later transported elsewhere by the blood vessels. PMID- 4042135 TI - Structural and biochemical differentiation of the guinea-pig colon during foetal development. AB - We have studied some aspects of the morphological and biochemical differentiation of the foetal guinea-pig colonic epithelium. At day 40 the epithelium was organised in ridges and appeared pseudo-stratified. Folding of the epithelium, followed by villus formation, occurred between days 45 and 55, and by day 50 mucus-secreting goblet cells appeared at the bases of the colonic villi. By day 55 most epithelial cells, including goblet cells, possessed numerous microvilli which, by day 65, had become organised into well developed brush-borders. Between day 55 and term (day 65-68) mucosal depth increased markedly and the colon attained its final glandular morphology. Biochemical studies showed the specific activities of the microvillar hydrolases to be much lower in the washed colon than in either foetal meconium or small intestine at all times during development. Furthermore, a membrane fraction highly enriched in microvillus hydrolase activities was prepared from foetal colonic meconium using techniques originally devised to isolate the foetal small intestinal microvillus membrane. This meconial subfraction was almost identical in polypeptide composition to the highly-purified foetal small intestinal microvillus membrane. Identification of the colonic microvillus membrane was hampered by the absence of reliable membrane markers. Nevertheless, a fraction 14-fold enriched in aminopeptidase activity was prepared from day 40 foetal colon and its polypeptide composition compared by SDS PAGE to that of the small intestinal microvillus membrane at the same age. PMID- 4042137 TI - Fine structural aspects of the shift of zonula occludens and cytoorganelles during the inversion of cell polarity in cultured porcine thyroid follicles. AB - Porcine thyroid follicles, when isolated by enzymatic digestion and suspended in Eagle's MEM containing 10% fetal calf serum, undergo inversion of cellular polarity. After isolation, the strands for the tight junctions (zonulae occludentes) between follicle cells begin to move towards the side of the medium and gather at this side of the lateral plasma membrane during 24 h of incubation. Around this time, microvilli of many follicular cells protrude into the culture medium. The elements of the Golgi apparatus are located at the luminal as well as the culture-medium side of the cytoplasm, and also at the lateral side of the nucleus after 24 h of suspension culture, and by 94 h of incubation almost all elements of this organelle, as well as lysosomes and the central cilium have migrated to the side of the medium. The migration of the zonulae occludentes is considered to be the initial change in the reversal of the polarity of this cell. PMID- 4042139 TI - Ultrastructural organization of the glomerular basement membrane as revealed by a deep-etch replica method. AB - The fine structure of the glomerular basement membrane was re-evaluated by using a deep-etch replica method. The structure of the laminae rarae interna and externa of the rat glomerular basement membrane was basically identical in that 6 to 8 nm fibrils were interconnected to form a three-dimensional, polygonal network. The size of the mesh was quite variable but most often ranged from 20 to 25 nm in width. In addition, a zipper-like substructure of the epithelial slit diaphragm was observed. By contrast, the lamina densa was composed of closely packed particles. After exposure of the bovine glomerular basement membrane to ultrasonic waves or trypsin, the particles of the lamina densa were effectively removed. The underlying structure showed the fibrillar network closely resembled that seen in the laminae rarae of the rat glomerular basement membrane. The glomerular basement membrane thus revealed was as principally composed of a fibrillar network, which might be regularly arranged units of type-IV collagen. Numerous fine particles, most likely proper components of the glomerular basement membrane, were attached onto this basic fibrillar structure, giving rise to a morphologic appearance different from that of the laminae rarae. PMID- 4042138 TI - Can cells extruded from denervated skeletal muscle become circulating potential myoblasts? Implications of 3H-thymidine reutilization in regenerating muscle. AB - The hypothesis that satellite cells which leave denervated skeletal muscle might become circulating potential myoblasts which could participate in myogenesis in distant sites in the body has been tested. Sixteen mice had one hindlimb denervated and were given 7 daily injections of 3H-thymidine (3H-Tdr). One day later extensor digitorum longus muscle isografts from unlabelled mice were inserted into each hindlimb. As controls, the procedure was repeated in 6 non denervated labelled mice. Fourteen days after their insertion, isografts in denervated mice contained many labelled myotubes with a labelling index of 55 +/- 4% (mean +/- SEM). In the control isografts in non-denervated ice, 38 +/- 4% of myotube nuclei were labelled. The results show that either labelled cells, or 3H Tdr, had transferred from the host to isografts in both cases. The probability of 3H-Tdr reutilization was demonstrated in regenerating livers of 8 similarly labelled mice, where 34 +/- 3% hepatocytes adjacent to crush lesions were labelled after 14 days. This conclusion was reached because only 2-3% of normal hepatocytes incorporate 3H-Tdr under these conditions and this population is inadequate to provide sufficient labelled precursor cells for the large numbers of labelled regenerated hepatocytes. Therefore, it was concluded that 3H-Tdr reutilization is the most likely explanation for labelled myotube nuclei in the muscle isografts (rather than movement of labelled precursor cells), and that additional label for reutilization had been derived from breakdown of labelled cells in denervated muscle. The data do not support the hypothesis of a circulating precursor for skeletal muscle cells. PMID- 4042140 TI - Lamina propria of intestinal mucosa as a typical reticular tissue. A scanning electron-microscopic study of the rat jejunum. AB - The three-dimensional architecture of the lamina propria in the jejunal mucosa of the rat was studied by scanning electron microscopy. The lamina propria is a typical reticular tissue with fine nets of reticular fibers and free and fixed cells lying among them. However, the lamina propria in the core of villi displayed structural features closer to other reticular or lymphoid tissues than that among the crypts. In the villi, the tissue was supported by a spongy framework of interconnecting fibroblasts, and densely infiltrated by free cells. Among the crypts, cellular elements were rather sparsely dispersed in a complex network of reticular fibers. A thin layer of reticular fibers lined the basal lamina of the epithelium. This layer contained a network of flattened cells which anastomosed with each other via slender processes. The basal lamina and the fibrous layer were perforated with round pores, through which free cells or basal processes of the epithelial cells passed. Many macrophages were found resting on the reticular framework of the lamina propria, frequently in close association with immunoblast-like cells. This paper further includes scanning electron microscopic observations on the central lacteal with special reference to its luminal projections and trabeculae. PMID- 4042141 TI - Ultrastructural changes associated with K+-evoked peptide secretion from a neurohemal organ of the crab, Cardisoma carnifex. AB - Electron-microscopic comparison of K+-stimulated and unstimulated crab sinus glands reveals significant differences in neurosecretory terminal morphology. Sinus glands exposed to elevated K+ saline for increasing periods of time show increasing numbers of exocytotic release profiles, vacuoles, and multilamellate bodies, and a decrease in the number of microvesicles within 10 micron of release sites. These morphological changes are well correlated with secretion of red pigment-concentrating hormone, as determined by bioassay of perfusate from the individual preparations. PMID- 4042142 TI - Calcium-sensitivity of brain microtubule proteins in the presence of S-100 proteins. AB - In the presence of the usual 0.1 M Mes buffer, pH 6.7, mM free Ca2+ levels are required for half-maximal decrease in the rate and extent of brain microtubule protein (MTP) assembly in the absence of ox brain S-100, while microM free Ca2+ levels are sufficient in the presence of S-100. At the same pH 6.7, but in the presence of 0.12 M KCl, as low as 1.5 microM free Ca2+ is sufficient for S-100 to produce half-maximal reduction in the rate of assembly, while as high as 0.5 mM free Ca2+ is required in the absence of S-100. Similar results are obtained with rat brain S-100 (S-100b), indicating that single S-100 iso forms are equipotent in affecting the MTP assembly. At pH 7.5, MTPs are remarkably resistant to Ca2+ in the absence of S-100. In the presence of S-100, not only is the free Ca2+ concentration required for complete inhibition of assembly at least one order of magnitude smaller than that required in the absence of S-100, but significant S 100-dependent inhibition of assembly occurs in the absence of Ca2+. Under the two conditions where S-100 is particularly effective in inhibiting the assembly, i.e. at pH 6.7 in the presence of KCl and at pH 7.5, S-100 increases the disassembly rate even in the presence of microM Ca2+ levels. Our results suggest that the free Ca2+ concentration regulates the way S-100 disassembles microtubules (MTs): at microM Ca2+ levels, S-100 sequesters tubulin with concomitant increase in the disassembly rate; at mM Ca2+ levels, the S-100-Ca2+ complex probably interacts with MTs producing endwise disassembly. PMID- 4042143 TI - A versatile and quantitative computer-assisted photoelectronic technique used for the analysis of ciliary beat cycles. AB - The beat cycles of rabbit tracheal cilia in culture and Mytilus laterofrontal cirri were recorded using a phototransistor, transillumination, video, and phase contrast microscopy. The photoelectronic signal and video image of the ciliary activity were simultaneously recorded as a composite image. The photoelectronic signal was converted into a digital signal by a data acquisition system for further computer processing. By the selection of a small detector area and accurate detector alignment, a simple, repetitive photoelectronic signal representing ciliary activity was obtained. This signal records the ciliary beat frequency and demonstrates the triphasic nature of the beat cycle. The photoelectronic signal can be precisely correlated with the ciliary activity by analysis of the composite video recordings to provide the duration of the effective, recovery, and rest phases of the beat cycle. The video-photoelectronic signal correlations were verified by high-speed cinematography. High-speed films of ciliary activity were digitized, and the image density of selected pixels was analyzed by computer with respect to time and ciliary motion. These studies indicate that duration of the phases of the beat cycle are differentially reduced with increased beat frequency; the effective phase duration was quickly reduced to a minimum. This was followed by the reduction of the duration of the recovery phase to a minimum. The rest phase continues to be reduced without reaching a minimum, over the range of beat frequencies observed. These results suggest that ciliary beat frequency may be regulated either by modifying the rates of dynein microtubule interactions or the rate of transition from one beat phase to the next. PMID- 4042144 TI - Actin assembly and filament cross-linking in the presence of TW 260/240, the tissue-specific spectrin of the chicken intestinal brush border. AB - TW 260/240 is a tissue-specific spectrin found in the terminal web region of the chicken intestinal brush border. We have examined the effects of TW 260/240 on assembly rates and critical concentrations (Co's) for monomer addition at the barbed and pointed ends of the actin filament. For these studies, acrosomal processes (AP) from Limulus sperm were used as nuclei for actin assembly. Under conditions which favor the interaction of TW 260/240 for actin (20-75 mM KCl, 2 mM Mg++) no effect on either elongation rates or Co's at either end of the actin filament was observed in the presence of this spectrinlike protein. The Limulus AP nucleation assay also allowed visualization of the kinetics of filament binding and cross-linking by TW 260/240. Ultrastructural analysis of TW 260/240 binding to actin filaments at their growing ends indicates that TW 260/240 tetramers bind laterally to the filament. Finally, evidence is presented that indicates that filaments cross-linked by TW 260/240 are stabilized against shear dependent breakage. PMID- 4042145 TI - Management and pregnancy outcome in eclampsia at Harare Maternity Hospital. PMID- 4042147 TI - Sensitivity to antibiotics of bacteria isolated in the Public Health Laboratory, Harare. PMID- 4042146 TI - Boomslang bite--a case report. PMID- 4042148 TI - Crocodile (Crocodylus niloticus) bile acids and arrow poisons. PMID- 4042149 TI - Fournier's gangrene in Dar Es Salaam. PMID- 4042150 TI - Optimal age for vaccinating Zimbabwean children against measles. Part I & II. PMID- 4042151 TI - Giardiasis, diarrhoea and malnutrition. PMID- 4042152 TI - Thermographic and pupillary asymmetry in chronic paroxysmal hemicrania. A case study. AB - Facial temperature was measured thermographically and pupillary diameter recorded photographically during and between episodes of headache and during spontaneous remission of headache in a patient with chronic paroxysmal hemicrania (CPH). Heat loss from the orbit, nose, cheek and temple was 0.75-1.5 degrees C greater on the symptomatic side during headache, and 0.25-0.75 degrees C greater between headache episodes. Heat loss from these regions of the face was symmetrical during remission of headache. Extensive rhinorrhoea, and slight ptosis and miosis were observed during the active phase of CPH. These findings, which are similar to those previously reported in cluster headache, suggest that CPH is associated with an ocular sympathetic deficit and with overactivity in the greater superficial petrosal nerve. PMID- 4042153 TI - Migraine art. AB - An analysis is made of 207 drawings and paintings entered for a migraine art competition. All types of visual disturbances were depicted. One hundred and fifty-four of the paintings showed spectral appearances with fortification or teichopsia in 99. Sixty-two showed either a partial or complete hemianopic loss. Metamorphopsia was seen in 32 and pain was depicted in some form or another in 80. Situational or trigger factors were shown in 23. PMID- 4042154 TI - Headaches and stress in schoolchildren: an epidemiological study. AB - Headache parameters, personality variables and stress factors were assessed in a sample of about 2,300 school pupils between 10 and 17 years of age in Amsterdam. More than 15% of the subjects reported headaches occurring weekly. Fear of failure and school problems, but not achievement motivation, had significant positive correlations with headache complaints after correction for differences in sex and age. Menarche and social class had little bearing in relation to the headache variables. From all reported causes of headache, stress was mentioned most frequently in both elementary and secondary schools. PMID- 4042155 TI - Coronary angiography and intracoronary thrombolytic therapy in the coronary care unit: an alternative approach. AB - The feasibility, safety and efficacy of performing left heart catheterization, coronary angiography, and intracoronary thrombolytic therapy in the coronary care unit setting were examined in 17 patients with acute ischemic syndromes presenting at a time when routine catheterization facilities were not available. In all cases, cardiac catheterization and coronary angiography were performed in the coronary care unit without difficulty using a portable image intensifier and a portable video recording system, and selective intracoronary streptokinase was safely administered in 13 patients with a total coronary occlusion, with successful thrombolysis in seven patients (54%). No adverse effects attributable to the performance of these procedures in the coronary care unit were observed. This approach might allow for a more prompt response and wider availability of intracoronary thrombolytic therapy for patients presenting with acute myocardial infarction. PMID- 4042156 TI - Heparin elimination following continuous infusion during intra-aortic balloon counterpulsation. AB - The decline of the activated partial thromboplastin time (APTT) following discontinuation of heparin infusion was measured in six intra-aortic balloon pump (IABP) patients. The heparin infusion requirement was determined for eight other IABP patients during stable therapeutic anticoagulation. Following discontinuation of infusion, APTT declined with a relatively constant half-life (t 1/2 of 2.4 +/- 0.08 hr, suggesting elimination by first-order kinetics. In comparison, the t 1/2 following single bolus doses has been shown to be markedly dose dependent, increasing from 30 min at low doses to 2 hr at very high doses. The heparin requirement for IABP patients was found to be 16 +/- 2.5 U/kg/hr, similar to that reported for other clinical situations. The t 1/2 of the APTT following discontinuation of heparin infusion can be used to time invasive procedures that would best be done with normal hemostasis. PMID- 4042157 TI - The role of intravenous streptokinase in acute arterial occlusions after cardiac catheterization. AB - Arterial occlusions after cardiac catheterization are usually treated surgically. We report four patients with femoral thrombosis or distal emboli that developed after cardiac catheterization. Each patient was treated successfully with intravenous streptokinase. Therapy was initiated 1-60 hr after the procedure. The duration of infusion lasted 4-42 hr (mean 27 hr). Pulses were restored 4-19 hr (mean 10 hr) after the beginning of infusion. There was no major hemorrhagic complication, even in patients with very early streptokinase infusion. Thus intravenous streptokinase may be an alternate choice to surgery for arterial occlusions after invasive procedures. PMID- 4042158 TI - Acute anterior myocardial infarction complicated by mural thrombus and peripheral thromboembolism despite anticoagulation. AB - A 43-year-old man had transmural anterior wall myocardial infarction complicated by hypotension and anterior-apical aneurysmal formation. Despite continuous anticoagulation with heparin sodium (heparin) and warfarin sodium (coumadin), a large pedunculated left ventricular thrombus was formed. Four hours after uneventful left ventriculography, the patient experienced acute superior mesenteric embolism. An emergency mesenteric embolectomy and then left ventricular aneurysmectomy with clot evacuation were performed to save the bowel and to prevent further embolization. PMID- 4042159 TI - A modified catheter system for retrograde left ventricular catheterization in aortic valve stenosis. AB - Conventional retrograde catheterization of the left ventricle using a single large catheter through severely stenotic aortic valves or prostheses has recognized difficulties. An alternative method is described. This method incorporates a coronary angioplasty guide catheter and coronary probing catheter attached to separate pressure transducers allowing simultaneous recording or aortic and LV pressures. This technique was used in seven patients with aortic stenosis in whom a conventional approach had failed. The movable probing catheter permits alterations of the catheter orientation and angulation while the guiding catheter stabilizes the system within the high velocity jet formed in the ascending aorta. This stabilization and the small size of the coronary probing catheter permit exploration of the valve surface and allow for insertion through a tilting disc valve or a severely stenotic valve without significantly altering hemodynamic function. In our laboratory this technique allowed us safely and reliably to assess aortic valve dynamics in each of the patients in whom the technique was attempted without resorting to either transseptal or direct left ventricular puncture. PMID- 4042161 TI - Percutaneous brachial catheterization. PMID- 4042160 TI - Injection of contrast medium within the interatrial septum. PMID- 4042162 TI - Pattern of protein synthesis in dissociated embryonic cells of Xenopus laevis whose reaggregation was inhibited by Ca2+-deprivation and by mechanical interference. AB - Protein synthesis was studied in dissociated Xenopus embryonic cells whose reaggregation was inhibited either chemically (deprivation of Ca2+) or mechanically (cultivation on sintered glass filter). Under reaggregation inhibited conditions, synthesis of several proteins was inhibited in neurula but not in blastula and gastrula cells. Under reaggregating conditions, pattern of protein synthesis in blastula cells became 'neurula-cell-type' after 17 h. However, under non-reaggregating conditions, activation of many proteins was inhibited. The inhibition was mostly reversible and similar to that observed in neurula cells inhibited by actinomycin D. Thus, synthesis of many proteins directed by new transcripts at the neurula stage appears to depend on the maintenance of cell-to-cell contact. PMID- 4042163 TI - Monoclonal antibodies against Dictyostelium plasma membranes: their binding to simple sugars. AB - Monoclonal antibodies raised against purified membranes from Dictyostelium discoideum were classified according to three criteria: type of antigen as revealed in immunoblots, developmental regulation of the target antigens, and location of the antigens on the cell surface. Some antibodies reacted with myosin, two with glycolipids. One group of antibodies bound to the protein moiety of the contact site A glycoprotein, whereas another group reacted with carbohydrate epitopes that the contact site A glycoprotein shared with a few other membrane glycoproteins. Binding of the latter antibodies to their antigens was either specifically blocked by N-acetylglucosamine or by maltose as well as methyl-alpha-mannoside and N-acetylglucosamine. These anti-carbohydrate antibodies bound specifically to agarose beads derivatized with some sugars. These results and competition studies with several carbohydrates suggest that the epitope recognized by the antibodies contains as major components N acetylglucosamine, maltose and alpha-mannose residues. One monoclonal antibody, which reacts with N-acetylglucosamine, was used for affinity purification of the contact site A glycoprotein from a crude membrane extract. N-acetylglucosamine was used as a mild eluent of the antigen from the antibody column. No detergents were added during the entire purification procedure. PMID- 4042164 TI - Evaluation of the sensitive step of inhibition of chondrogenesis by retinoids in limb mesenchymal cells in vitro. AB - The sensitive step of inhibition of chondrogenesis in vitro by retinoids was investigated in modified micromass cultures of limb bud mesenchymal cells from mouse embryos of day 11 and 12. Evaluation of chondrogenesis was performed after alcian blue staining, using a simple random hit counting of cartilage nodules. All-trans-retinoic acid, 13-cis-retinoic acid, and a newly developed arotinoid, RO 13-6298, were tested for their ability to inhibit chondrogenesis. We found that inhibition of chondrogenesis depended on the dosage and the duration of treatment with the different retinoids. Further analysis showed that chondrogenesis in limb bud mesenchymal cells from the proximal part was irreversibly inhibited after one hour of treatment, whereas distal cells showed a reduction of cartilage development only after a treatment period of 12 and more hours. In respect to the doses of the retinoids, proximal cells were about one magnitude more vulnerable than distal cells. These proximo-distal differences were obtained with 13-cis-retinoic acid at 10 micrograms/ml, with all-trans retinoic acid at 1 microgram/ml and with arotinoid RO 13-6298 with 10 ng/ml. It is supposed that the late blastemal stage of chondrogenic differentiation before the onset of matrix synthesis is the step which is most vulnerable to retinoid treatment. PMID- 4042165 TI - Synaptic inhibition and cell communication; impairment of cell-to-cell coupling produced by gamma-aminobutyric acid (GABA) in the somatic musculature of Ascaris lumbricoides. AB - The influence of gamma-aminobutyric acid (GABA) (10(-5) M) on the electrical coupling of giant somatic muscle cells of Ascaris lumbricoides was investigated. GABA enhanced the resting potential of the cells and abolished the spike activity. The coupling coefficient (V2/V1) was reduced by 58.8% while the input resistance (Rin) was decreased by 38.8%. The decline in Rin was not related to unlinearity of the current-voltage relation. As the time constant of cell membrane was reduced by 28.4% by the addition of GABA the effect of the neurotransmitter on cell-to-cell coupling seems to be mainly related to a decrease in resistance of the non-junctional membrane due to an increase in chloride conductance. PMID- 4042166 TI - Cell-to-cell electrical coupling in seminiferous cords of mouse fetal testis. AB - Experiments performed on mouse fetal testes in vitro using electrophysiological techniques and intracellular injections of the fluorescent tracer disodium fluorescein showed that junctional transfer occurs between cells inside the seminiferous cords. This suggests a possible metabolic cooperation between testis cells at an early stage of gonad development. PMID- 4042168 TI - Organelle motility in rat pituitary clonal cells. I. Dynamic movements of intracellular organelles. AB - Intracellular organelle motion within clonal pituitary tumor cells (GH3) was observed directly with a contrast enhancement, computer-video microscope system. All particles except nuclei moved in a complex fashion. Two types of particles predominated; one large and round, the other small and elongated. We classified the movements of these particles as saltation, oscillation and slow translocation. Saltation was directional movement with velocity of the order of 1 micron/sec. Oscillation was local motion occurring within 1 micron that showed no specific direction. Its velocity was similar to that of saltation. Large particles, in particular, showed the 3rd type of movement, slow translocation. The velocity appeared to be one order slower than that of saltation. We also examined the cells with fluorescent, dark-field and electron microscopies. We concluded that the large round particles were lysosomes and the small elongated ones mitochondria. The microtubule depolymerizer, vinblastine and the microfilament depolymerizer, cytochalasin D, completely inhibited all the types of organelle movement. The mechanism and significance of these organelle movements are discussed. PMID- 4042169 TI - [How shall we further improve the care of women with gynecologic malignancies?]. PMID- 4042167 TI - Does freeze-substitution reveal the hydrophobic nature of interprotofilament bonding in microtubules? AB - The massive system of microtubules in the ovarioles of Notonecta glauca has been prepared for electron microscopy by means of freeze-substitution. With this technique the protofilaments comprising the microtubule walls can be observed in positive image, indicating that the procedure provides a valuable method for observing microtubule substructure. Surprisingly though, the cryoprotectants, which are an integral part of the method, caused a rearrangement of the microtubules from their usual pattern in the ovarioles. These observations, we believe, provide an insight into intra- and intermicrotubule interactions respectively. PMID- 4042170 TI - [Delivery after intrauterine embryo transfer obtained by fertilization and oocyte culture in vitro]. PMID- 4042171 TI - [The effect of long-term tocolytic therapy on the cardiovascular system in pregnant women]. PMID- 4042173 TI - [Acupuncture in the treatment of female incontinence]. PMID- 4042172 TI - [Is episiotomy still important?]. PMID- 4042174 TI - [Actinomycoses of the female genitalia in connection with IUD insertion]. PMID- 4042175 TI - [Chronic and recurrent vaginal mycoses and the immune system]. PMID- 4042176 TI - [The effect of alcohol on the hypothalamo-hypophyseal-ovarian axis]. PMID- 4042177 TI - [Results and perspectives in therapeutic embryo transfer]. PMID- 4042178 TI - [The first embryo transfer, pregnancy and childbirth in a woman with premature menopause]. PMID- 4042179 TI - [The views of the author of the feedback theory of pain on labor pain and labor psychoprophylaxis]. PMID- 4042180 TI - [What should the physician's role be in regulating fertility and sex behavior (a contribution for discussion)]. PMID- 4042181 TI - [SolcoTrichovac--a new trend in the immunotherapy of urogenital trichomoniasis?]. PMID- 4042182 TI - [Gastrointestinal hormones]. PMID- 4042183 TI - [Hypoxic pulmonary vasoconstriction]. PMID- 4042184 TI - [Levels of aldosterone in the blood of healthy calves and goats]. PMID- 4042185 TI - [Phacoemulsification of the rabbit lens in vivo]. PMID- 4042186 TI - [Defects in the nerve fibers of the retina and changes in computerized perimetry in the beginning stages of simple glaucoma]. PMID- 4042187 TI - [Glaucoma and retinal detachment]. PMID- 4042188 TI - [Changes in iris pigmentation in Czechoslovak children]. PMID- 4042189 TI - [Circulating immunocomplexes in uveitis]. PMID- 4042190 TI - [First aid in chemical injuries of the eye]. PMID- 4042191 TI - [Pencil points--modification of the contact test for examining stereopsis]. PMID- 4042192 TI - [A visit by Czechoslovak ophthalmologists to the Soviet Union]. PMID- 4042193 TI - [The neonate at risk and his evaluation by the pathologist. Introduction]. AB - Children with a low birth weight represented a minimal part of neonates but they shared substantially in neonatal mortality. To unify the opinion about causes of neonatal death seemed to be urgent when comparing figures from various institutes. PMID- 4042194 TI - [Biometric data of normotrophic neonates]. AB - Gestation age of a neonate could be estimated approximately by a pathologist according to some macroscopical features. In addition to the weight of large organs the authors studied weight of other organs and some biometrical data in a group of 84 normotrophic neonates. Regressive analysis gave information about the growth trend of organs; compared with tables it enabled to find out the growth retardation of a neonate or his single organ. The span of fingers represented a precise statistical figure for the estimation of gestation age in addition to the weight of organs. PMID- 4042195 TI - [Diagnosis and classification of pulmonary findings in neonates]. AB - Developmental phases could be defined in neonatal lung tissue fixed in situ or in an ordinary way: glandular lung, canalicular lung with simple tubes covered by cuboid epithelial cells, alveolar lung with usual complicated structure. Canalicular lung could manage the blood saturation which depends on the number of capillaries. There was a different picture of alveoli filled with fluid or air. Hyaline membranes, always occurring in fluid-filled alveoli, represented a barrier for drainage of intraalveolar fluid. Step-wise inflation of lung enabled a histomechanical examination giving lately "functional" figures. They showed a poor functional readiness as well as a quick postnatal adaptability of immature lung. Pressure-volume curves correlated with histological maturity and pathological finding offered a more comprehensive explanation of clinicopathological mechanisms. PMID- 4042196 TI - [Evaluation of the mucosal surface relief of the small intestine in neonates]. AB - Immature neonates have slim thread-like villi of uniform length. More matured children have rougher villi with initial club-like expansion of the tip. Later there is a triangular broadening at the base of villi and at last tongue-shaped villi occur. They develop quickly in early days of life of an immature child and simultaneously with broader square villi and crest-like formations. This phenomenon is far more expressed in immature neonates than in matured ones. PMID- 4042197 TI - [Evaluation of kidney maturity in neonates]. AB - Morphometric analysis of glomeruli allows to estimate renal maturity or find out an accidental retardation of growth. A simpler estimation of the number of yalers formed by immature glomeruli is less time-consuming. Final diagnosis of pathologist should include this estimation. An intense growth of glomeruli does not start before glomerular lobulation concurring with an increase of capillary lumina in a glomerular square unit. So lobulation expresses generally the maturity of glomeruli. PMID- 4042198 TI - [Sequence of vascular closing mechanisms beginning post partum]. AB - Ductus arteriosus, ductus venosus and umbilical vessels were studied in a group of 120 children deceased in perinatal period and 30 persons deceased at the age of 1 month till 90 years. Time sequence of evident morphological closing of vessels was analyzed. A contraction of media and proliferation of intima finished at the end of the 1st month were found in all of them except in ductus arteriosus where it finished at the end of the 3rd month. Dystrophic changes of proliferating structures were found in following months. Closing of ductus arteriosus started in an antenatal phase by pillow-like proliferation of intima. A primary thrombosis closing the vessels was extremely rare. There was not any difference between immature and hypotrophic or mature and eutrophic neonates. PMID- 4042199 TI - [Morphologic analysis of the thymo-lymphatic status in neonates and in early childhood]. AB - Lesions of B- and T-systems as well as of suprarenal cortex were studied in a group of 31 children (at the age of 2 days till 3.5 years) suffering from thymolymphatic state and correlated with their basic disease. 25 cases were of a secondary type, 6 cases belonged to an idiopathic (primary) type. Secondary thymolymphatic state mostly occurred with inflammatory diseases of the respiratory system and was characterized by a B-system exhaustion, T-system activation and suprarenal atrophy. Idiopathic thymolymphatic state found in sudden and unexpected deaths was combined with variegated B-reactin and T-system activation. Insufficiency of immune reactions (morphological as well as functional) and suprarenal cortical atrophy could contribute to the cause of death. PMID- 4042200 TI - [Criteria for neonatal maturity. Conclusions for practice]. AB - The evaluation of neonatal maturity is an important condition for interpretation of pathologist's findings. Weight of organs and other biometrical data, histological evaluation of maturity in various organs and rebuilding of circulation give objective morphological criteria of maturity as well as isolated retardation of growth or development. PMID- 4042201 TI - [Cardiac fibroma in a neonate]. AB - Fibroma of the interventricular septum 3 cm in diameter caused a heart failure in a 2-day-old neonate. The tumour infiltrated neighboring heart muscle the fibres of which grew atrophic. PMID- 4042202 TI - [Alveolar lipoproteinosis]. AB - The diagnosis of alveolar lipoproteinosis was established in a 46-year-old man's lung biopsy. The tissue was processed both for paraffin sections and electron microscopy. Morphology corresponded to the data in literature. Nevertheless, detailed clinical search and morphology failed to reveal causal factors. The case belonged to the group of alveolar proteinosis with uncertain etiopathogenesis. PMID- 4042203 TI - [Electron microscopy changes in hypophyseal lactotrophs in rats after the administration of metoclopramide]. AB - Metoclopramide (Cerucal - Germed) proved to cause an ultrastructural activation of lactotroph cells in rat males. It showed itself as an increase of granular endoplasmic reticulum forming long lamellar or spiral structures. Many lactotrophs had a conspicuous Golgi zone. Estrogens and Metoclopramide administered simultaneously manifested themselves in a picture of heightened activation. The findings concurred with immunohistochemical ones from the same group of animals which issued earlier. PMID- 4042204 TI - [Calcification in the heart. IV. Calcification of the pulmonary valve]. AB - A case is described of a 12-year-old girl suffering from Fallot's tetralogy whose atretic pulmonary valve was massively calcified. This appears to be the first case described of this condition in childhood. PMID- 4042205 TI - [Understanding and empathy as a method in psychopathology]. PMID- 4042206 TI - [The good psychiatrist]. PMID- 4042207 TI - [Ethical aspects as part of the professional approach in psychiatry]. PMID- 4042208 TI - [Factors in the pathogenesis of neuroses]. PMID- 4042210 TI - [Comparison of the results of computer tomography and pneumoencephalography in psychopathology and psychiatric nosography]. PMID- 4042209 TI - [Treatment of schizophrenia using hemodialysis]. PMID- 4042211 TI - [Lower cerebellar arteries in the diagnosis of infratentorial expansive processes]. PMID- 4042212 TI - [Radiodiagnosis of inflammatory pseudotumors of the pancreas]. PMID- 4042213 TI - [2-dimensional echoencephalography in early childhood]. PMID- 4042214 TI - [Comparison of the parenchymal phase of hepatobiliary gammagraphy with a radiocolloid gammagram of the liver]. PMID- 4042215 TI - [Modification of an industrial linear accelerator for therapeutic use]. PMID- 4042216 TI - Anti-ulcer effect of isoprenyl flavonoids. III. Synthesis and anti-ulcer activity of metabolites of 2'-carboxymethoxy-4,4'-bis(3-methyl-2-butenyloxy)chalcone. PMID- 4042217 TI - Identification of steroidal compounds as acetates in a lysate of "Depressor-I," an antihypertensive phospholipid occurring in acetone-soluble fraction of bovine brain. PMID- 4042218 TI - Total synthesis of (+/-)-silybin, an antihepatotoxic flavonolignan. PMID- 4042219 TI - Relationship of the structures of tannins to the binding activities with hemoglobin and methylene blue. PMID- 4042220 TI - Chemical transformation of protoberberines. VII. Efficient conversion of protoberberines into benzindenoazepines via 8,14-cycloberbines. PMID- 4042221 TI - Studies on the constituents of medicinal and related plants in Sri Lanka. III. Novel sesquilignans from Hedyotis lawsoniae. PMID- 4042222 TI - Synthesis and structure-activity study of protease inhibitors. IV. Amidinonaphthols and related acyl derivatives. PMID- 4042224 TI - Application of principal component analysis to the study of quantitative structure-activity relationships by means of multiple regression analysis. PMID- 4042223 TI - Antiulcer activity of dehydroabietic acid derivatives. PMID- 4042225 TI - Studies on active substances in the herbs used for oketsu ("stagnant blood") in Chinese medicine. II. On the anticoagulative principle in persicae semen. PMID- 4042226 TI - Studies on active substances in the herbs used for oketsu ("stagnant blood") in Chinese medicine. III. On the anticoagulative principles in curcumae rhizoma. PMID- 4042227 TI - Studies on active substances in the herbs used for oketsu ("stagnant blood") in Chinese medicine. IV. On the anticoagulative principle in rhei rhizoma. PMID- 4042228 TI - Studies on the constituents of asclepiadaceae plants. LVIII. The structures of five glycosides, cynatratoside-A, -B, -C, -D, and -E, from the Chinese drug "pai wei," Cynanchum atratum Bunge. PMID- 4042229 TI - Properties of hydrazones of hydralazine and colorimetric determination of hydralazine hydrochloride with p-dimethylaminocinnamaldehyde based on solvent extraction. PMID- 4042230 TI - Studies on analgesic oligopeptides. III. Synthesis and analgesic activity after subcutaneous administration of [D-Arg2]dermorphin and its N-terminal tetrapeptide analogs. PMID- 4042231 TI - The photochemical decomposition and hydroxylation of phenylalanine in the presence of riboflavin. PMID- 4042232 TI - Carbon-13 nuclear magnetic resonance spectral analysis of the fruit bodies of Grifola frondosa. PMID- 4042233 TI - Purification and characterization of alpha-L-fucosidase from the liver of seahare, Aplysia kurodai. PMID- 4042234 TI - Synthesis of the nonatetracontapeptide corresponding to the entire amino acid sequence of thymopoietin I and its effect on the low E-rosette-forming cells of a uremic patient. PMID- 4042235 TI - Effects of a cationic surfactant on the rate of alkaline hydrolysis of p substituted benzenesulfonyl fluorides. PMID- 4042236 TI - Study of crystalline drugs by means of a polarizing microscope. VI. Polarizing microscopy of drugs acting on the nervous system and on individual organs listed in the Japanese Pharmacopoeia X. PMID- 4042237 TI - Application of solid dispersions of nifedipine with enteric coating agent to prepare a sustained-release dosage form. PMID- 4042238 TI - Preparation of mean drug concentration--time curves in plasma. A study on the frequency distribution of pharmacokinetic parameters. PMID- 4042239 TI - The behavior of 1,4-benzodiazepine drugs in acidic media. II. Kinetics and mechanism of the acid-base equilibrium reaction of oxazolam. PMID- 4042240 TI - Prediction of available surface area of powdered particles of flufenamic acid in tablets. PMID- 4042241 TI - Effect of grinding on the transformations of polymorphs of chloramphenicol palmitate. PMID- 4042242 TI - Cholagogic action and characteristics of (+/-)-alpha-terpineol-beta-D-O glucopyranoside, a new monoterpenoid glucoside. PMID- 4042243 TI - Biologically active principles of crude drugs. Anti-allergic principles in "Cnidii monnieri". PMID- 4042244 TI - Effects of epoxidation on the actions of normorphine, norcodeine, N allylnormorphine(nalorphine) and N-allylnorcodeine on the electrically stimulated guinea pig ileum. PMID- 4042245 TI - High-performance liquid chromatographic determination of urinary metabolites of 2,4-dinitrotoluene in Wistar rats. PMID- 4042246 TI - A facile synthetic method for pyrimidine acyclonucleoside derivatives. PMID- 4042247 TI - Synthesis of some N-substituted 1,2,3,4,5,6-hexahydro-2,6-methano-3-benzazocines (6,7-benzomorphans). PMID- 4042248 TI - Reaction of amino acids with alkyl p-toluenesulfonates. PMID- 4042249 TI - Lactams. XXIV. Alkaline hydrolysis of 1-benzyl-2-piperidone derivatives: application to cis-trans isomerization of the 5-ethyl-2-oxo-4-piperidineacetic acid system. PMID- 4042250 TI - Natural antioxidants. III. Antioxidative components isolated from rhizome of Curcuma longa L. PMID- 4042251 TI - A new methodology for chemoselection of one amino and four hydroxyl groups of glucosamine derivatives and its use for synthesis of lipid X. PMID- 4042252 TI - Synthesis and characterization of a radioiodinated, photoreactive and physiologically active analogue of platelet activating factor. AB - The multistep synthesis of a photoreactive, radioactive and aggregating analogue of platelet-activating factor (PAF)-acether is described. The photoreactive and radioactive moiety was added at the last step; the specific radioactivity was higher than 1000 Ci/mmol. The concentration of this new analogue which causes 50% of aggregation of platelets were of the same order of magnitude as for synthetic snPAF-acether, so as for two other analogues having a bulky group at the omega end of the fatty ether chain. The photoreactivity was proved by the covalent binding of the analogue to protein (BSA) after 10-min irradiation times at 300 nm. The binding was largely prevented by prior (not by later) addition of a high concentration of lyso phosphatidyl choline. PMID- 4042253 TI - Interactions and space requirements of the phosphate head group in membrane lipids. The crystal structure of disodium lysophosphatidate dihydrate. AB - The packing arrangement and molecular conformation of lysophosphatidate (disodium 3-lauroyl-DL-glycero-1-phosphate dihydrate (LPA] was determined by single crystal analysis. The lipid crystallizes in the triclinic space group P1 with unit cell dimensions of a = 7.74, b = 5.54, c = 32.87 A and alpha = 92.6, beta = 99.2, gamma = 128.3 degrees. The molecules are arranged tail to tail in a bilayer structure. Thereby the D- and L-enantiomers pack separately in the opposite halves of the bilayer and are conformationally related by mirror symmetry. The hydrocarbon chains adopt the triclinic (T parallel) chain packing mode and are tilted by 55 degrees with respect to the layer normal. The phosphate groups are linked by one of the sodium ions to tightly packed rows. Between these rows the second sodium ion and the two water molecules of hydration are accommodated forming an extensive network of hydrogen, ionic and coordination bonds. The two sodium ions are positioned 1 A below and above the plane defined by the centres of gravity of the phosphate charges. The phosphate group and its 4 ligands thus pack effectively with a small cross-sectional area in the layer plane of 33.6 A2. PMID- 4042254 TI - D-dihexanoylphosphatidylcholine is not a pure competitive inhibitor of phospholipase A2 hydrolysis of L-dihexanoylphosphatidylcholine. AB - The inhibition of Crotalus adamanteus phospholipase A2 hydrolysis of L dihexanoylphosphatidylcholine by D-dihexanoylphosphatidylcholine was investigated with inhibitor and substrate in the monomeric concentration range. The results showed that the D-enantiomer acts as a partial (not pure) competitive inhibitor of the enzyme. These results suggest that an ESI complex exists, in which hydrolysis of the substrate still occurs. Thus, binding of the D-enantiomer to the enzyme decreases the affinity for the substrate by a factor, alpha, while Vmax is unaffected. The value of alpha was determined to be 4.70 +/- 0.14. These findings complicate the use of D-phosphatidylcholines in mixed micelles with the L-enantiomer as a possible method to investigate the mechanism of interfacial activation of this enzyme. PMID- 4042255 TI - [Cervical tumors of thymic origin in children]. AB - Cervical tumors of thymic origin are exceptional and can be either cystic or solid. The embryogenesis of the thymic gland explains the cervical location of these tumors. The authors present two cases in which the clinical picture was limited to cervical masses with very few symptoms. Treatment consisted of surgical removal. Subsequent course was uneventful without any immunological deficit or myasthenia. PMID- 4042256 TI - [The surgical form of the hemolytic-uremic syndrome]. AB - The hemolytic-uremic syndrome consist of micro-angiopathic hemolytic anemia, acute renal failure, and thrombocytopenia following a prodromal illness of gastroenteritis. The syndrome can present in dramatic fashion with severe abdominal pain and signs of peritonitis suggesting an acute surgical crisis. In some cases, laparotomy is necessary, and we report a case with colectomy. PMID- 4042257 TI - [Laryngo-tracheo-esophageal cleft associated with missed atresia]. AB - Laryngo-tracheo-esophageal cleft (LTEC) is a rare malformation. Treatment is always surgical and still has uncertain results. One case of LTEC (type III), associated with a "missed atresia" of the esophagus is reported. The diagnosis of eso-tracheal, H-Type fistula was first suspected at birth before transfer of the baby to the neonatal surgery department where the diagnostic of long LTEC was established. Surgical repair was done through lateral cervicotomy and allowed complete cure of the eso-tracheal communication without tracheotomy. Barium swallowing, controlled on the eleventh post-operative day, showed a perfect result of the reconstruction and an underlying esophageal malformation, previously described as "missed atresia". The treatment of this second malformation was performed two months later by plain resection-anastomosis with excellent outcome at a one year follow up with no recurrent fistula nor GE reflux or laryngeal nerve palsy. To the best of our knowledge, this type of association has not been previously reported. PMID- 4042258 TI - [Ethical and legal problems posed by the prenatal diagnosis of abnormalities. Medical data]. PMID- 4042259 TI - [Ethical problems posed by the prenatal diagnosis of abnormalities. The ethical problem]. PMID- 4042260 TI - [Ethical and legal problems posed by the prenatal diagnosis of abnormalities. Legal aspects]. PMID- 4042261 TI - [The calcium bile syndrome in children]. AB - The "limy bile" is uncommon in adults and very exceptional in childhood. The authors report a new case of a 7 years old girl. The review of the literature since Churchman's description (1911) allowed to collect eleven other cases of children, less than fifteen old. The usual sexual distribution in biliary diseases with female predominance is not true for them: eight boys for four girls. The youngest was three years and six months old. All but one have presented mainly right upper abdominal pain and vomiting. The diagnosis was made by an abdominal plain film showing a spontaneous visualization of the gallbladder which contained a material made of carbonate of calcium. One was an operative detection. All presented a stone of neck of gallbladder or cystic duct. The origin of "limy bile" is unknown. Nine children have been operated (cholecystectomy) with good result. Spontaneous disappearance of "limy bile" was noted in three cases. It was marked by acute abdominal pain, inconstant jaundice or pancreatic reaction. No surgical care was brought with nor further problems or recurrence. PMID- 4042262 TI - [Esophageal peristalsis and acid clearance. A study method]. AB - Peristaltic waves account for clearance of acid refluxed into the oesophagus, acting as a second anti-reflux barrier. We have developed a system combining oesophageal motor and pH studies. We use a three-lumen, constantly perfused, manometry probe attached to a pH microelectrode. Primary and secondary oesophageal waves are able to clear injected acid from the oesophagus, whilst non propulsive tertiary waves do not raise pH back to normal levels. Children with severe GER have a high proportion of tertiary waves, and it is tempting to incriminate these motor disturbances as an important for their bad tolerance to GER. PMID- 4042263 TI - [Surgical pulmonary biopsy in children]. AB - During the last 2 years an open lung biopsy was performed in 16 children aged from 2 to 14 years. Fourteen of these had a chemotherapeutic induced immunodeficiency and a radiological picture of diffuse pulmonary infiltrate. A definite diagnosis was established in 11 cases: 5 pneumocystis carinii pneumonitis, 2 CMV infections, 2 pneumocalcinosis, 1 neoplastic pulmonary lymphangitis and 1 staphylococcal infection. Three had a non-specific interstitial pneumonitis. In this series there was no post-operative death and the single complication was a wound infection. The tracheal tube could be removed within the hours following the intervention in 14 of the 16 children. The review of the recent literature suggests that the open lung biopsy is a safe and accurate way for the diagnosis of pulmonary infiltrates in pediatric immunocompromised patients. It is however a very invasive procedure and it is expectable that in the next year the bronchoalveolar lavage with a fiberoptic flexible bronchoscope will be systematically attempted prior to the open biopsy. PMID- 4042264 TI - [Principles of the surgical treatment of cloacal malformation. Apropos of 3 cases]. AB - The persistent cloaca is one of the most complex and challenging developmental malformation. It is a rare anomaly occuring only in the female newborn and represented by the association of a urogenital sinus with an anorectal malformation. We report here three cases seen and recently treated in Montpellier (France) in the unit of visceral pediatric surgery (Pr J.G. Pous) between 1981 and 1983. A precise knowledge of normal embryology is very helpful in order to understand these complex anatomical situations. Every case is probably unique, but some main principles of management can be stressed. Neonatal loop colostomy is probably safer in most cases and can allow temporizing until the child is 6 months to 1 year of age. Interim management is often needed: intermittent catheterisation of the bladder and/or urine-filled vagina via the uro-genital sinus, avoiding urinary diversions, except possible temporary supra-pubic cystostomy. Definitive reconstruction is often a long and complex procedure, strictly dependent on absolutely thorough radio-endoscopic pre-operative investigations. It is vital to know exactly the length of the cloacal canal and of the urethra, because surgical reconstruction will vary according to the level at which the various structures converge. Cloacas represent a wide anatomic spectrum: as the severity of the defect increases, there is urogenital sinus with anterior anus ("Near cloacal malformation"), low and high confluence of all three systems. The goal of surgery is to perform in a single operation, the separation of the different conduits and to preserve all the sphincteric mechanisms for urinary-anal continence and genital functions.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4042265 TI - [Frequency of congenital abnormalities in the Grand Duchy of Luxembourg. Apropos of 7015 births occurring from 1980 to 1982]. PMID- 4042266 TI - [Malaria in 1985: new recommendations]. PMID- 4042267 TI - [Anatomic basis of x-ray computed tomography of the heart and coronary arteries]. PMID- 4042268 TI - [Coronary aneurysmal disease]. PMID- 4042269 TI - [How to protect the traveler against malaria in 1985]. PMID- 4042270 TI - [Genetic polymorphism of drug metabolism: therapeutic implications]. PMID- 4042271 TI - Characterization of a microsomal fraction from rat small intestine for metabolic activation of some promutagens. AB - Rat small intestine possesses cytochrome P-450 mixed function oxidase activity and is thus potentially capable of activating procarcinogens during absorption. The low spontaneous tumour incidence at this site may be due partially to the detoxification activity of the intestinal mucosa. To study the contribution of the intestine to the metabolism of foreign chemicals, microsomes have been obtained from rat small intestine by a procedure facilitating recovery of preparations with consistently high enzyme activities and abilities to activate some selected promutagens in the Salmonella mutagenicity assay. Intestinal microsomes from animals with and without pretreatment with inducers have been used for investigations of biochemical properties and ability to activate several mutagens in the Salmonella plate incorporation assay. The effects of microsomal protein concentration and inhibitors were also studied. The results are compared with data obtained using liver microsomes from the same animals. Despite the induction of lower numbers of revertants, intestinal microsomes were at least as efficient as liver preparations for the activation of all the promutagens used when the data were corrected for cytochrome P-450 contents. Differences in dose response curves for certain mutagens using liver and intestinal microsomes are discussed in relation to variation in metabolism of promutagens. Activation was linearly dependent on microsomal protein concentration, for both liver and small intestinal microsomes. The intestine was generally less susceptible to the effects of cytochrome P-450 and P-448 inducers, although sensitivity to orally administered phenobarbitone was increased by extending treatment times. SKF525A and beta-naphthoflavone inhibited microsomes from both sources, equal inhibition being observed for each type following incorporation of the inhibitor, although they differed in their ability to activate 2-acetylaminofluorene in the presence of the deacylase inhibitor, NaF. The data are discussed in relation to the possible role of the small intestine in metabolic activation in vivo and the utility of microsomes therefrom for the in vitro detection of putative dietary carcinogens. PMID- 4042272 TI - The toxic response of preneoplastic rat tracheal epithelial cells to 12-O tetradecanoylphorbol-13-acetate. AB - The purpose of our studies was to examine the effect of 12-O-tetradecanoylphorbol 13-acetate (TPA) on survival, proliferation, and differentiation of normal and preneoplastic rat tracheal epithelial (RTE) cells. Normal RTE cells obtained from 8-week-old rats were plated into medium containing TPA at concentrations ranging from 0.1 to 100 ng/ml. A dose-related increase in colony-forming efficiency (CFE) was observed at concentrations above 0.1 ng/ml. At 100 ng/ml the CFE was increased 5-fold above that observed in controls. Similar studies were carried out with immortal, preneoplastic RTE cells derived from carcinogen-exposed primary cultures. Upon exposure to 10 ng/ml of TPA, 9 out of 11 cell lines showed a marked decrease in CFE ranging from a 70 to a greater than 99% reduction. Two out of 11 cell lines showed only a minor reduction in CFE at this TPA concentration. Teleocidin B was as potent as TPA in causing inhibition of CFE in preneoplastic RTE cells; the potency of 4-O-methyl TPA was approximately 1/100 that of TPA and phorbol was virtually inactive. Further studies suggested that inhibition of clonal growth of the preneoplastic tracheal cells by TPA was due to rapid cell death. As early as 2 h after addition of TPA to the cultures, a loss of viable cells from the cultures as well as a reduction in CFE was observed. Morphological studies support the interpretation that a large number of cells was severely damaged within 2--4 h after TPA exposure. The formation of cross-linked envelopes (CLE), a measure of keratinocyte differentiation, was determined in cultures of preneoplastic RTE cells. TPA caused only minor increases in CLE formation indicating that the cells were not dying from TPA-induced terminal keratinocyte differentiation, but rather from TPA toxicity. Thus, preneoplastic RTE cells respond differently to TPA from normal RTE cells and also from normal and transformed keratinocytes of various origins. The role of TPA toxicity in promoting preneoplastic RTE cells to the neoplastic state is being investigated. PMID- 4042273 TI - The conditions for the modification of radiation transformation in vitro by a tumor promoter and protease inhibitors. AB - These experiments were designed to define the conditions necessary for the modification of radiation-induced transformation in C3H/10T1/2 cells by TPA and protease inhibitors. The results show that: (i) the lowest effective dose of various protease inhibitors to suppress transformation in vitro varies over several orders of magnitude; on a molar basis, the inhibitors of chymotrypsin appear to be the most effective protease inhibitors at suppression of radiation induced transformation in vitro, (ii) the protease inhibitors antipain and the Bowman-Birk (soybean) protease inhibitor have no effect on radiation transformation when present only during irradiation, (iii) the protease inhibitor antipain can suppress radiation transformation in vitro when applied to proliferating "initiated' cells as late as 10 days and 13 cell divisions post irradiation, and (iv) TPA treatment following a 10-day protease inhibitor (anti pain) exposure of X-irradiated "initiated' cells does not lead to promotion in vitro. These results suggest that protease inhibitor treatment of the initiated cells has irreversibly reverted cells to their original or "uninitiated' condition which existed before irradiation. PMID- 4042274 TI - Tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced chromosome aberrations in mouse keratinocyte cell lines: a possible genetic mechanism of tumor promotion. AB - The effect of the tumor promoter, 12-O-tetradecanoyl-phorbol-13-acetate (TPA) on the induction of numerical and structural chromosomal aberrations, double minute chromosomes (DM) and homogeneously staining regions (HSR) was investigated in two mouse keratinocyte cell lines (HEL-30 and HEL-37) using G- and C-banded chromosomal preparations. The frequency of polyploid metaphases and of structural aberrations increased several fold during the first two cell cycles. The increase of gaps, chromatid and isochromatid breaks was accompanied by inter- and intrachromosomal exchanges, which were virtually absent in control cultures. The induction of chromosomal aberrations was similarly expressed in both cell lines at different passage levels and was largely independent of the TPA dose applied (10(-9) - 10(-6) M). The non-promoting phorbolester 4-O-methyl-TPA (10(-6) M) did not produce any chromosomal aberrations above the control level. Effects were already visible within one cell cycle (24 h) after treatment and increased with longer and multiple exposure. Moreover, the TPA-induced chromosomal aberrations persisted for several days after elimination of the promoter and further cultivation of cells in fresh medium. Structural alterations were not randomly distributed but chromosomes 1 and 2 were preferentially involved in breaks, while chromosomes 1-3 and 9-13 were mainly involved in chromosomal exchanges. Chromosomes 7 and 14, which are numerically underrepresented in HEL cells, were least involved in breaks. Most interesting, the frequency of metaphases carrying DMs increased 2- to 3-fold after TPA treatment, and the alterations were partially reversible after removal of TPA. These early effects of TPA at the chromosomal level could play an essential role in the mechanism of tumor promotion and may be responsible for the observed persistence of alterations induced during the first stage of tumor promotion. PMID- 4042275 TI - Quantitative aspects of enhanced liver tumour formation in CF-1 mice by dieldrin. AB - The dose-response characteristics of dieldrin-mediated enhancement of liver tumour formation in CF-1 mice were analysed, using existing tumour data from chronic feeding studies at six levels of continuous exposure, involving a total of greater than 1500 animals. The dose-response relationship can be expressed as: Dx X Tx = D0 X T0 = constant, where T0 = the median liver tumour induction period in control CF-1 mice, Tx = the median liver tumour induction period in dieldrin treated mice at a dose level Dx, D0 = the background dose equivalent for the induction of 'spontaneous' liver tumours, Dx = the sum of background dose (D0) and actual dieldrin dose (delta x). The relationship, which is a Druckrey equation (D X Tn = constant) where n = 1, indicates that: (i) the velocity of liver tumour development is proportional to the daily dose level (Dx), (ii) the total tumourigenic dose is constant across all doses, (iii) the effects of dieldrin on the neoplastic process in mouse liver are essentially irreversible and cumulative, and (iv) there is no evidence for a threshold level. However, when delta x much less than D0, the actual contribution of dieldrin to tumour formation is expected to be negligible. PMID- 4042276 TI - Toxic chemicals in sediments and biota from a creosote-polluted harbor: relationships with hepatic neoplasms and other hepatic lesions in English sole (Parophrys vetulus). AB - High prevalences of idiopathic hepatic lesions, including neoplasms (e.g., hepatocellular carcinomas, cholangiocellular carcinomas) (27%, 20 of 75 fish) and foci of cellular alteration (putative 'preneoplastic' lesions) (44%, 33 of 75 fish), were found in English sole (Parophrys vetulus) exposed to creosote contaminated sediments in Eagle Harbor, Puget Sound, WA. Sediments from the contaminated region of the harbor contained particularly high concentrations of aromatic hydrocarbons (e.g., benzo[a]pyrene and benz[a]anthracene), and a variety of nitrogen-containing aromatic compounds (e.g., carbazole and acridine). The composition of the aromatic compounds was characteristic of creosote. Dramatically lower concentrations of aromatic compounds were found in sediments from a reference site in which the bottom-dwelling fish examined were free of detectable neoplastic or 'preneoplastic' hepatic lesions. Food organisms in the stomachs of the English sole from Eagle Harbor contained substantially higher concentrations of aromatic hydrocarbons than comparable organisms from the reference site. The concentrations of individual aromatic hydrocarbons in muscle and liver from the Eagle Harbor fish were low; however, high concentrations of metabolites of aromatic compounds were present in the bile. The findings strongly suggest an association between exposure to creosote and the prevalence of hepatic lesions, including neoplasms, in the bottom-dwelling fish, and furthermore support the putative role of aromatic hydrocarbons in liver carcinogenesis in fish. PMID- 4042277 TI - Pulmonary response of hamsters to fibrous glass: chronic effects of repeated intratracheal instillation with or without benzo[a]pyrene. AB - Syrian golden hamsters were given intratracheal instillations of glass fibres with or without benzo[a]pyrene suspended in saline, once a fortnight for 52 weeks. The experiment was terminated at week 85. 'Silicotic granulomas' consisting of tightly packed, iron-positive macrophages filled with glass fibres and surrounded by a layer of alveolar epithelial cells were the predominant pulmonary lesion. No mesotheliomas or other tumours of the respiratory tract were observed in hamsters treated with glass fibres alone. There was no indication that glass fibres enhanced the development of respiratory tract tumours induced by benzo[a]pyrene. In hamsters similarly exposed to crocidolite fibres with or without benzo[a]pyrene no mesotheliomas or other respiratory tract tumours were observed either. An explanation for the absence of pulmonary tumours might be that repeated administration of fibres over a period of 52 weeks entails an acute pulmonary reaction after each administration with the implication that the fibres cannot settle down well enough to be able to induce tumours. Another possible explanation is the relatively short duration of the experimental period. PMID- 4042278 TI - Effect of nicotine and N'-nitrosonornicotine on rat lung and trachea ornithine decarboxylase activity. AB - The exposure of rats to tobacco smoke was previously reported to cause an increase in lung and trachea ornithine decarboxylase (ODC) activity. In the present paper we test the effects of the tobacco-specific components nicotine and N'-nitrosonornicotine (NNN) on lung and trachea ODC activity. In addition, a procedure for the synthesis of analytically pure NNN is described. NNN caused an increase in lung ODC activity 6 h and also 4 days after a single s.c. dose. NNN did not alter trachea ODC activity. A single s.c. dose of nicotine activated both lung and trachea ODC in a dose-response fashion. It is possible that the impact of these tobacco-specific agents upon respiratory tract polyamine biosynthesis could contribute to some of the multi-faceted effects associated with cigarette smoking. PMID- 4042279 TI - Induction of hepatic cell proliferation and unscheduled DNA synthesis in mouse hepatocytes following in vivo treatment. AB - We have modified the in vivo-in vitro hepatocyte DNA repair assay for measurement of unscheduled DNA synthesis (UDS) and hepatic cell proliferation in B6C3F1 mice. Dimethylnitrosamine and methylmethane sulfonate produced significant increases in UDS in both rats and mice. 2-Acetylaminofluorene induced a significant increase in UDS in rats, but not in mice. The mouse hepatocarcinogens, carbon tetrachloride, trichloroethylene, polybrominated biphenyls and 2,6-dichloro-p phenylenediamine all failed to induce UDS in male and female mice, but all induced significant elevations in hepatic cell proliferation. Increased cell turnover in the liver may therefore be an important mechanism in hepatocarcinogenicity in the mouse. PMID- 4042280 TI - Dependence of u.v.-induced DNA excision repair on deoxyribonucleoside triphosphate concentrations in permeable human fibroblasts: a model for the inhibition of repair by hydroxyurea. AB - We have tested the hypothesis that the inhibition by hydroxyurea of repair patch ligation and chromatin rearrangement during u.v.-induced DNA excision repair results from a reduction in cellular deoxyribonucleotide concentrations and not from a direct effect of hydroxyurea on the repair process. Using permeable human fibroblasts, we have shown that hydroxyurea has no direct effect on either repair synthesis or repair patch ligation. We also have shown that by reducing the deoxyribonucleoside triphosphate concentrations in the permeable cell reaction mixture, we can mimic the inhibition of repair patch ligation and chromatin rearrangement seen when u.v.-damaged intact confluent fibroblasts are treated with hydroxyurea. Our results are consistent with the concept that hydroxyurea inhibits DNA repair in intact cells by inhibiting deoxyribonucleotide synthesis through its effect on ribonucleotide reductase and, conversely, that continued deoxyribonucleotide synthesis is required for the excision repair of u.v.-induced DNA damage even in resting cells. PMID- 4042281 TI - Syncarcinogenic effects of methyl methanesulfonate with methylazoxymethanol acetate in rat small intestine and liver. AB - The carcinogenic potency of methyl methanesulfonate (MMS) and its combination effect with methylazoxymethanol (MAM) acetate were evaluated in rats. MMS was suggested to be weakly carcinogenic for the small intestine. Syncarcinogenic effects of MMS and MAM acetate which could be due to summation of their genotoxic influences were obtained in the small intestine and liver. PMID- 4042282 TI - Role of adenosine on ventricular overdrive suppression in isolated guinea pig hearts and Purkinje fibers. AB - The present study was undertaken to demonstrate and characterize potentiation of ventricular overdrive suppression by adenosine. To substantiate that adenosine has an enhanced effect on overdrive suppression, it would be necessary to demonstrate that adenosine increases pause duration independent of slowing spontaneous pre-drive rate. In isolated perfused guinea pig hearts with surgically induced complete atrioventricular block, the effect of adenosine (2-20 microM) on pause duration was compared to two alternative means of slowing the pre-drive rate, i.e., hypothermia (28.0 degrees C to 34.0 degrees C) and cesium chloride (0.3-1.0 mM). The slope value of the linear regression line describing the relationship between pre-drive cycle length and pause duration for adenosine (15.8) was significantly greater than control (1.7), hypothermia (1.7), and cesium chloride (5.4). The competitive adenosine antagonist, aminophylline (60 microM), when infused at the initiation of overdrive during adenosine administration, significantly reduced the effect of adenosine on pause duration by 72.9 +/- 4.2% (mean +/- SEM). The reduction in pause duration by aminophylline was specific for adenosine and did not occur under control conditions or during cesium chloride administration. During hypoxia, aminophylline and adenosine deaminase, when infused at the initiation of overdrive, caused 72.3 +/- 5.6 and 63.3 +/- 6.1% reductions in pause duration, respectively. Endogenous adenosine levels rose significantly with hypoxia (1,687 +/- 202 vs. 36 +/- 4 pmol/min per g during normoxia) and increased significantly further during hypoxic overdrive (3,004 +/- 323 pmol/min per g). In isolated guinea pig Purkinje fibers (n = 4), adenosine (20 microM) increased pause duration by 73.6 +/- 9.9% while only minimally affecting the pre-drive cycle length (7.6 +/- 3.8%). These fibers, when stimulated at 1.5 Hz, also displayed an adenosine-induced reduction in action potential duration at 90% repolarization (16 +/- 2 msec). In addition, we demonstrated that adenosine had an enhanced effect on pause duration in the presence of ouabain (1 microM)-induced attenuation of overdrive suppression. Thus, in isolated Purkinje fibers, it is unlikely that the potentiating effect of adenosine on pause duration, which is independent of its chronotropic effect, is mediated via an enhancement of sodium potassium adenosine triphosphatase pump activity. The effect of adenosine is likely to be secondary to a direct action on outward potassium conductance.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 4042283 TI - Effect of development on coronary vasodilator reserve in the isolated guinea pig heart. AB - Morphological studies have demonstrated an age-related decrease in capillary density and capillary surface area in the developing heart. However, the consequences of these changes on myocardial perfusion are not known. We tested the hypothesis that the decreased capillary density is associated with a reduction in coronary blood flow reserve. To test this hypothesis, we studied coronary responses to adenosine and sodium nitroprusside administration, reactive hyperemia, and autoregulatory capacity. We used a Langendorff-perfused heart preparation from guinea pigs of five different age groups (1 week and 1, 2, 12, and 18 months). Data are expressed as mean +/- SEM. Maximal coronary flows (ml/min per g) in response to adenosine (10(-6) to 10(-5) M) infusion are: 27 +/- 1.3, 18.5 +/- 1.4, 12.2 +/- 0.4, 10.3 +/- 0.3, and 10.6 +/- 0.8 at 1 week, 1, 2, 12, and 18 months, respectively, with the flows at 1 week and 1 month significantly higher than those at 2, 12, and 18 months. There is a similar trend for a decreased maximum coronary perfusion in response to sodium nitroprusside (10(-6) to 10(-5) M) and following a 45-second occlusion of the coronary inlet flow. Despite the decreased maximal pharmacological and reactive hyperemic flow reserve, autoregulation of flow is not altered with growth. The pressure-flow relationship exhibits autoregulation between 25 and 55 mm Hg perfusion pressure for all but the 1-week age group, which autoregulates within a narrower range of pressures (20-45 mm Hg). Total maximal coronary flow (ml/min) increases during development; this indicates that the growth of vessels continues with development.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4042284 TI - Effects of reperfusion after coronary artery occlusion on post-infarction scar tissue. AB - Early reperfusion after a coronary occlusion may reduce myocardial infarct size, but late reperfusion into necrotic myocardium may alter post-infarction healing. In rabbits, we compared 1- or 3-week-old scars resulting from permanent coronary occlusion to those resulting from a 1- or 3-hour occlusion followed by reperfusion. Reperfusion at 1 hour post-occlusion did not affect scar mechanical properties assessed at 1 week post-infarction, but at 3 weeks post-infarction, these scars had a tensile strength significantly lower than those not reperfused (78 +/- 11 vs. 158 +/- 15 g/mm2, P less than 0.001). They also were composed of a mixture of fibrous tissue (58 +/- 8%) and myocytes (43 +/- 8%) with a hydroxyproline content of 23 +/- 2.5 mg/g dry weight. The nonreperfused scars had a higher proportion of fibrous tissue (73 +/- 3%) by histological evaluation and a 35% higher hydroxyproline content (31 +/- 2 mg/g dry weight, P less than 0.001) than the scars reperfused after 1 hour. In contrast, 3-week-old scars resulting from "late" reperfusion at 3 hours post-occlusion were similar to nonreperfused scars in fibrous tissue composition and hydroxyproline content. Nonetheless, the tensile strength of these scars reperfused 3 hours post-occlusion was significantly less than that of the nonreperfused scars (72 +/- 5 vs. 158 +/- 15 g/mm2, P less than 0.001). The lower tensile strength was associated with a lower collagen cross-link density in this reperfused group of scars. At physiological stress levels (approximately 3 g/mm2), all groups of reperfused and nonreperfused scars had similar mechanical properties in terms of natural strain, stiffness, creep, and stress relaxation. Thus, although the reperfused scars ruptured more easily at high stresses, when assessed at physiological stresses their mechanical properties were not significantly different from those of nonreperfused scars. PMID- 4042285 TI - The role of oxygen-derived free radicals in ischemia-induced increases in canine skeletal muscle vascular permeability. AB - Previous studies indicate that vascular permeability is increased in skeletal muscle subjected to 4 hours of inflow occlusion. However, the mechanism(s) underlying the increase in permeability are unknown. The aim of this study was to assess the role of oxygen-derived free radicals and histamine as putative mediators of the increased permeability in skeletal muscle subjected to 4 hours of inflow occlusion. The osmotic reflection coefficient for total plasma proteins and isogravimetric capillary pressure were estimated in canine gracilis muscle for the following conditions: control, ischemia, and ischemia plus pretreatment with allopurinol (a xanthine oxidase inhibitor), catalase (a peroxidase that reduces hydrogen peroxide to water and molecular oxygen), superoxide dismutase (a superoxide anion scavenger), dimethyl sulfoxide (a hydroxyl radical scavenger), diphenhydramine (a histamine H1-receptor blocker), or cimetidine (a histamine H2 receptor blocker). Ischemia, followed by reperfusion, significantly reduced the reflection coefficient from 0.94 +/- 0.02 to 0.64 +/- 0.02 and isogravimetric capillary pressure from 13.8 +/- 1.0 mm Hg to 6.9 +/- 0.4 mmHg, indicating a dramatic increase in microvascular permeability. Prior treatment with diphenhydramine or cimetidine did not significantly alter the permeability increase induced by ischemia. However, pretreatment with allopurinol, catalase, superoxide dismutase, or dimethylsulfoxide did significantly attenuate the increase in vascular permeability. The results of this study indicate that oxygen radicals are primarily responsible for the increased vascular permeability produced by ischemia-reperfusion, that the hydroxyl radical may represent the primary damaging radical, and that xanthine oxidase may represent the primary source of oxygen-derived free radicals in ischemic skeletal muscle. PMID- 4042286 TI - The renal sympathetic baroreflex in the rabbit. Arterial and cardiac baroreceptor influences, resetting, and effect of anesthesia. AB - Curves relating renal sympathetic nerve activity and mean arterial pressure were derived in conscious rabbits during ramp changes in mean arterial pressure, elicited by perivascular balloon inflation. The renal sympathetic nerve activity mean arterial pressure relationship consisted of a high-gain sigmoidal region about resting, where renal sympathetic nerve activity rose or fell in response to moderate falls and rises of mean arterial pressure. With larger pressure rises, renal sympathetic nerve activity first fell to a lower plateau and then reversed at even higher mean arterial pressure. When mean arterial pressure was lowered below resting, renal sympathetic nerve activity rose to an upper plateau and then reversed abruptly toward resting at low mean arterial pressure. Both arterial and cardiac baroreceptors exerted substantial inhibitory influences on renal sympathetic nerve activity at all pressure levels. These effects appeared additive over the central high gain region of the curve, but beyond this region there were non-additive interactions. The latter were affected considerably by alfathesin anesthesia. In other experiments, we studied the effects of sustained alterations in resting mean arterial pressure induced by infusing nitroprusside and phenylephrine, which produced rapid resetting of the renal baroreflex. The latter could be accounted for, in part, by resetting of the threshold of the arterial baroreceptors and in part by contributions from other afferents, probably the cardiac receptors. During resetting associated with nitroprusside induced falls in resting blood pressure, high-gain reflex adjustments in renal sympathetic nerve activity to moderate changes in mean arterial pressure were preserved, but during resetting associated with phenylephrine-induced rises in resting mean mean arterial pressure, the resting renal sympathetic nerve activity lay on the lower curve plateau, resulting in reduction in the apparent gain of the reflex renal sympathetic nerve activity response to moderate changes in mean arterial pressure. PMID- 4042287 TI - American Heart Association. Abstracts. 58th scientific sessions of the American Heart Association. November 11-14, 1985, Washington, D.C. PMID- 4042288 TI - Effects of sublingual nifedipine on hemodynamics and systolic and diastolic function in patients with hypertrophic cardiomyopathy. AB - The hemodynamic effects of sublingual nifedipine were examined in 36 patients with hypertrophic cardiomyopathy. Twenty-one patients were initially given 20 mg and 15 patients were given 10 mg of the drug; 30 min after this first dose 26 patients received 10 mg and one patient 20 mg as a second dose. Hemodynamic findings in patients who received different doses of the drug were similar. Peak effects included an increase in heart rate from 79 +/- 12 to 91 +/- 14 (mean +/- 1 SD) beats/min (p less than .01), and a decrease in mean blood pressure from 89 +/- 12 to 77 +/- 10 mm Hg (p less than .01). Cardiac index increased after nifedipine (2.8 +/- 0.6 to 3.3 +/- 0.8 liters/min/m2; p less than .01); stroke volume index, however, did not change (36 +/- 7 to 36 +/- 8 ml/beat/m2; NS). Peripheral vascular resistance index fell significantly from 822 +/- 261 to 610 +/- 197 dynes X sec X cm-5 (p less than .01). Overall, left ventricular outflow tract gradient (LVOTG) did not change in patients with significant (greater than or equal to 30 mm Hg) basal LVOTG (75 +/- 22 to 83 +/- 22 mm Hg; NS), but it increased significantly in those six patients in whom peripheral vascular resistance fell by 25% or more (73 +/- 28 to 99 +/- 22 mm Hg; p less than .05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4042289 TI - Global and regional right ventricular function in normal infants and infants with transposition of the great arteries after Senning operation. AB - Echocardiographic assessment of right ventricular size, global function, and regional wall motion was performed in 29 normal infants and 19 infants with transposition of the great arteries 1 to 41 months after they underwent the Senning procedure. Sixteen of the patients with transposition of the great arteries were in clinically good condition and three had congestive heart failure. The right ventricular endocardial surface was digitized frame by frame for a complete cardiac cycle in both subxiphoid long-axis (coronal plane) and short-axis (parasagittal plane) views, and the cross-sectional area and the area change fraction (AF) were calculated. In each plane the right ventricular wall was subdivided into four anatomic regions (infundibular, free wall, diaphragmatic, and septal). With the use of a floating point center of mass model the direction and average extent of motion of the endocardium was determined for each region. In normal infants the infundibular and free wall portions of the right ventricle exhibited the greatest inward motion and the septal segments the least inward motion. Although the maximal area in both long-axis (r = .85) and short-axis (r = .85) views was highly correlated with body surface area (BSA), neither global nor regional function was significantly correlated with age or BSA. In clinically well patients after Senning procedure regional right ventricular function followed an entirely different pattern than that seen in normal infants. The endocardium of the septal segments showed the greatest inward motion in systole. In contrast to those in normal infants, maximal and minimal cross-sectional areas did not correlate significantly with BSA.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4042290 TI - Intraoperative detection of myocardial ischemia in high-risk patients: electrocardiography versus two-dimensional transesophageal echocardiography. AB - Because acute segmental wall motion abnormalities (SWMAs) of the left ventricle are highly sensitive and specific indicators of myocardial ischemia, this study compared the incidence and significance of ischemia, as detected by two dimensional transesophageal echocardiography and surface electrocardiography, during anesthesia and surgery in patients at high risk of myocardial ischemia. During surgery, 24 of the 50 patients studied had new SWMAs, whereas only six had ST segment changes. All patients with ST segment changes also had new SWMAs: in three instances, SWMAs occurred before the ST segment change, and in three instances, they occurred simultaneously. All three patients who had intraoperative myocardial infarctions also had persistent intraoperative SWMAs, whereas only one patient had ST segment changes. Ten healthy patients requiring noncardiovascular surgery were monitored similarly; none of these had SWMAs, ST segment changes, or myocardial infarction. This study demonstrates the superiority of two-dimensional transesophageal echocardiography over electrocardiography for the intraoperative detection of myocardial ischemia. Furthermore, when new SWMAs persist to the conclusion of surgery, myocardial infarction is likely to have occurred. PMID- 4042291 TI - Transcutaneous oxygen recovery and toe pulse reappearance time in the assessment of peripheral vascular disease. AB - The accuracy of measurements of transcutaneous oxygen tension (Ptco2) in the diagnosis of peripheral vascular disease (PVD) may be significantly increased by stressing limb circulation with the use of temporary ischemia. The purpose of this study was to compare the transcutaneous oxygen recovery half-time (TORT) and the toe pulse reappearance time (PRT/2) in a series of patients with symptomatic PVD before and after vascular reconstruction. The TORT was defined as the time required to recover half of the decrease in the limb/chest Ptco2 ratio caused by temporary limb ischemia, and is conceptually comparable to the toe PRT/2, the time required to recover half of the control toe pulse amplitude. Measurement of TORT was found to be more feasible (100% vs 58%) and to have a greater diagnostic yield (100% vs 92%) than that of the toe PRT/2. When measured on the dorsum of the foot, TORT values were found to correlate well with the severity of symptoms of PVD; toe PRT/2 values did not correlate with severity of symptoms. Patients who underwent successful vascular reconstruction had significant improvement in their calf and foot TORT values after surgery (p less than .005 and .0005, respectively); postoperative values were similar to those obtained in normal subjects. Toe PRT/2 values usually improved postoperatively, but in many patients postoperative values overlapped with values that were considered abnormal. There was no overlap of TORT values in normal subjects with those in patients with symptomatic PVD. The measurement of TORT may be clinically useful for screening patients with suspected PVD and for assessing quantitatively the results of conservative and surgical therapy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4042292 TI - Computer detection of atrioventricular dissociation from surface electrocardiograms during wide QRS complex tachycardias. AB - Differentiation of wide QRS complex tachycardias on surface electrocardiograms is difficult for physicians and computers due in part to their inability to identify atrial activity, specifically atrioventricular (AV) dissociation. We studied 20 examples of AV associated rhythms and 17 examples of AV dissociated ventricular tachycardia. We applied an algorithm consisting of subtraction of a mean beat from each individual beat in leads II and V1 to generate remainder electrocardiograms. The remainder electrocardiograms were visually inspected for the presence of P wave candidates and then autocorrelated. AV dissociated P wave candidates were evident on visual inspection of remainder electrocardiograms in none of 20 AV associated and 15 of 17 AV dissociated rhythms. Atrial cycle length and the presence of AV dissociation were automatically detected by applying a peak selection algorithm to the autocorrelation function. AV association was detected in all 20 AV associated rhythms and AV dissociation was detected for 11 of 17 AV dissociated rhythms (sensitivity 65%, specificity 100%, positive and negative predictive accuracy 100%, 77%). The correlation coefficient of detected vs true atrial cycle length for the 11 correctly detected AV dissociated rhythms was r = .98. Visual inspection of the remainder electrocardiograms along with the original electrocardiogram may increase the ease with which human readers can identify the presence of AV dissociation and thus diagnose ventricular tachycardia. Computer diagnosis of wide QRS complex tachycardias should be significantly improved by use of this algorithm. PMID- 4042293 TI - Maintenance of exercise stroke volume during ventricular versus atrial synchronous pacing: role of contractility. AB - Although atrial synchronous and rate-responsive ventricular pacing have been compared, the importance of maintaining synchronized atrial systole in addition to rate responsiveness has been incompletely defined. That is, the effects of these two pacing modes on cardiac volumes and contractility have not been studied. Accordingly, 16 patients with normal ventricular function were studied while in the upright position and at rest with gated radionuclide ventriculography during both atrial synchronous and ventricular pacing. Twelve of these patients were also studied during low-level upright exercise (300 kilopond meters). Rest and exercise ventricular pacing heart rates were matched to those recorded with synchronous pacing. Ventricular volumes were determined with a counts-based method. The ejection fraction and peak systolic pressure/end systolic volumes or contractility between the two pacing modes. However, during exercise to identical heart rates, blood pressures, and workloads, although stroke volume was the same during exercise with atrial synchronous and ventricular pacing (78 +/- 13 vs 75 +/- 12 ml), end-diastolic and end-systolic volumes were lower with ventricular pacing than with atrial synchronous pacing (end-diastolic volume 101 +/- 13 vs 113 +/- 16 ml, p less than .001; end-systolic volume 26 +/- 4 vs 35 +/- 7 ml, p less than .001). Stroke volume during ventricular paced exercise was maintained at atrial synchronous pacing levels by means of increased contractility (ejection fraction of 74 +/- 4% during ventricular pacing vs 69 +/- 5% during atrial synchronous pacing, p = .002; peak systolic pressure/end-systolic volume ratio of 6.51 +/- 1 during ventricular pacing vs 4.85 +/- 1 during atrial synchronous pacing, p less than .001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4042294 TI - The effects of the rate of intravenous infusion of streptokinase and the duration of symptoms on the time interval to reperfusion in patients with acute myocardial infarction. AB - We studied the influence of the following variables on the time interval from initiation of an intravenous infusion of 750,000 U of streptokinase until reperfusion (reperfusion time) in 140 consecutive patients with an evolving acute myocardial infarction: (1) the rate of infusion of streptokinase, (2) the duration of chest pain before initiation of treatment, (3) patient age, (4) patient sex, (5) location of infarction, (6) history of previous myocardial infarction, and (7) pretreatment pathologic Q waves. The time of reperfusion was recognized by clinical criteria that were completely concordant with the anatomic findings in all 119 patients in whom patency or occlusion of the artery of infarction was established at delayed angiography (n = 116) or at postmortem examination (n = 3). The mean reperfusion time for the 129 patients for whom data were available was 49 +/- 36 min. The reperfusion time was inversely related to the rate of infusion of streptokinase (r = .41, p less than .001), but this effect of infusion rate appeared to plateau at rates of greater than 500 U/kg/min. In the 64 patients receiving infusions at rates of 500 U/kg/min or less, the mean reperfusion time was 60 +/- 40 min, whereas in the 58 patients receiving the drug at rates greater than 500 U/kg/min it was 35 +/- 22 min (p less than .001). The duration of chest pain before treatment was the only other studied variable found to influence the reperfusion time, but only at infusion rates of less than 250 U/kg/min (r = .6, p less than .01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4042295 TI - Effects of intravascular volume state on the value of pulsus paradoxus and right ventricular diastolic collapse in predicting cardiac tamponade. AB - Both pulsus paradoxus and right ventricular diastolic collapse detected by two dimensional echocardiography are noninvasive markers of impaired cardiac function in cardiac tamponade, yet the reliability of each may vary with the patient's state of hydration. To examine the relative value of these noninvasive markers at various states of hydration, we studied five chronically prepared, conscious mongrel dogs during 37 episodes of cardiac tamponade at three different intravascular volumes. We continuously measured cardiac output (electromagnetic flowmeter), aortic blood pressure, right atrial blood pressure, intrapericardial pressure, and respirations. Intravascular volume was varied by adjusting the mean right atrial blood pressure to hypovolemic (-2 to -6 mm Hg), euvolemic (0 to 4 mm Hg), or hypervolemic (6 to 10 mm Hg) levels. The sensitivity and specificity of right ventricular diastolic collapse in predicting increases in intrapericardial pressure remained high at all levels of hydration. Pulsus paradoxus showed good sensitivity and specificity at low intravascular volumes, but both sensitivity and specificity declined at higher intravascular volumes. Thus right ventricular diastolic collapse was more sensitive and more specific than pulsus paradoxus in detecting increases in intrapericardial pressure during euvolemia and hypervolemia whereas the two tests were equally valuable in hypovolemic states. PMID- 4042296 TI - Comparison of pathologic and angiographic findings in a porcine preparation of coronary atherosclerosis. AB - Coronary atherosclerosis was induced in Yorkshire swine by diet-induced hyperlipidemia and balloon intimal abrasion of a coronary artery. Severe stenoses pathologically similar to the lesions of human atherosclerosis were seen after 8 months of the atherogenic regimen. To examine the relationship between the angiogram and pathology in the assessment of the extent and location of coronary atherosclerosis, antemortem angiographic results were compared with results of pathologic examination. Vernier caliper measurements of the coronary angiogram were compared with results of morphometric evaluation of perfusion-fixed coronary arteries. Isolated focal stenoses were correctly localized and quantified, as were focal lesions within vessels diffusely diseased. Both overestimation and underestimation of lesions occurred at bifurcation sites. Diffuse disease without focal stenoses was not well demonstrated angiographically. Vessels that were angiographically thought to be normal or only minimally diseased demonstrated significantly larger lumens angiographically than pathologically. This is believed to be due to fixation and paraffin-processing artifact, even though fixation was performed by perfusion at physiologic pressure. The demonstration of an excellent correlation between the luminal size as determined angiographically and morphometrically at sites of focal obstruction confirms the value of quantitation of coronary angiograms in vivo as a diagnostic tool in coronary atherosclerosis. PMID- 4042297 TI - Cesium chloride-induced long QT syndrome: demonstration of afterdepolarizations and triggered activity in vivo. AB - The identification of afterdepolarizations and their relationship to arrhythmias in vivo is not available. Experiments were undertaken to determine whether afterdepolarizations could be detected in monophasic action potentials (MAPs) recorded in vivo and whether they were related to arrhythmias in an intact canine preparation of the long QT syndrome. Isolated cardiac tissues from six dogs were studied to validate the technique. In simultaneous MAP and transmembrane recordings, afterdepolarizations induced with barium (early) or acetylstrophanthidin (delayed) were detected in MAPs when present in microelectrode recordings. MAPs were then recorded in situ in eight dogs with cesium chloride-induced long QT syndrome associated with ventricular arrhythmias. Afterdepolarizations were identified in each of the dogs and were similar to early afterdepolarizations identified in vitro; they occurred during phase 3 and were attenuated during overdrive pacing. The afterdepolarizations were closely related to arrhythmias: (1) afterdepolarizations always preceded ventricular arrhythmias, (2) the coupling intervals (CI) of the afterdepolarizations (AD) and the ventricular premature beats (VPB) were nearly identical (VPB CI = 1.06 AD CI 10.24; r2 = .87), (3) the take-off potentials of the ventricular premature beats were nearly identical to the amplitude of the afterdepolarizations (take-off potential = 0.98 afterdepolarization amplitude +0.46, r2 = .87), and (4) afterdepolarizations and ventricular arrhythmias resolved concurrently during overdrive pacing and with time. Thus, a new catheter technique has been validated and has been used to directly identify afterdepolarizations and triggered activity in vivo. PMID- 4042298 TI - Effects of right ventricular ischemia on left ventricular geometry and the end diastolic pressure-volume relationship in the dog. AB - We studied the effects of right ventricular ischemia on left ventricular three dimensional geometry and the end-diastolic pressure-volume relationship in 16 open-chest dogs before and after pericardiectomy. Left ventricular volume was calculated from three internal dimensions measured with ultrasonic crystals. In one group of eight dogs, right coronary artery (RCA) occlusion for 2 min with the pericardium intact reduced aortic flow by 24 +/- 9% (p less than .001) and septal lateral dimension by 8 +/- 5% (p less than .01), without changing anterior posterior and apical-basal dimensions. However, parameters of left ventricular systolic function (aortic flow, left ventricular systolic pressure, peak dP/dt, and mean percent systolic shortening) were similar to those observed at a comparable level of left ventricular end-diastolic volume during inferior vena caval occlusion. In the other group of eight dogs, during RCA occlusion before pericardiectomy the left ventricular end-diastolic pressure-volume relationship determined during rapid blood transfusion shifted leftward and upward significantly from the preocclusion relationship. After pericardiectomy, RCA occlusion caused less significant changes in aortic flow and septal-lateral dimension as well as in the left ventricular end-diastolic pressure-volume relationship. We concluded that right ventricular ischemia causes a leftward shift of the interventricular septum in end-diastole and an alteration of the left ventricular end-diastolic pressure-volume relationship without changing left ventricular myocardial performance. These changes are enhanced by the intact pericardium. PMID- 4042299 TI - Contrast echocardiographic estimation of regional myocardial blood flow after acute coronary occlusion. AB - Contrast echocardiography can predict pathologic area at risk during acute coronary occlusion. In this study we evaluated (1) whether the intensity and timing of contrast appearance in ischemic regions can provide a quantitative measure of residual myocardial perfusion, and (2) whether changes in these parameters observed after serial injections reflect changes in blood flow to acutely ischemic tissue. Supra-aortic hydrogen peroxide contrast echocardiography was performed in 12 consecutive dogs at 1, 20, and 120 min after acute circumflex coronary occlusion. Contrast enhancement was determined qualitatively with a segmental four-point scoring system based on the appearance time and peak perceived intensity of contrast enhancement and quantitatively with a computer algorithm designed to reflect these parameters. Comparison was made in each segment to concomitant radioactive microsphere blood flow. Qualitative scoring related systematically to normalized segmental blood flow (3+ = 93%; 2+ = 61%; 1+ = 32%; 0 = 18%; p less than .01 for each vs adjacent value), as did quantitative analysis including all segments (r = .78; p less than .01) and isolated to the ischemic region (flow = 1.13 intensity change +6.8%; r = .83, p less than .001). Changes in microsphere flow in ischemic regions between sequential observations were correlated with changes in qualitative score (r = .88, p less than .001) and results of quantitative analysis (r = 0.70, p less than .01). The amount of contrast enhancement can provide quantitative information about residual myocardial blood flow in ischemic regions and can also be used to track changing patterns of flow in vivo after acute coronary occlusion. PMID- 4042300 TI - Mechanisms of improving regional and global ventricular function by preload alterations during acute ischemia in the canine left ventricle. AB - We examined the influence of left ventricular end-diastolic pressure (LVEDP) on the mechanical interaction between ischemic and nonischemic areas during acute myocardial ischemia. Circumferentially oriented ultrasonic segment gauges were implanted in the midwall of the anterior apex and posterior apex of the left ventricle in seven anesthetized dogs. Stroke volume was measured with a flow probe around the ascending aorta in five of these animals. We varied LVEDP with vena caval occlusion and dextran infusions to three matched levels (7, 12, and 19 mm Hg) before and 30 min after complete occlusion of the mid left anterior descending coronary artery. With acute ischemia, the anterior apex or ischemic zone demonstrated marked segmental lengthening during isovolumetric systole (end diastole to aortic valve opening) and akinesis during the ejection phase (aortic valve opening to closure). In the posterior apex or nonischemic area, isovolumetric shortening increased and ejection phase shortening decreased during acute ischemia when compared with those under control conditions at the same LVEDP. Thus, a portion of the shortening generated by the nonischemic area was expended in stretching the ischemic zone during isovolumetric systole, thereby reducing the amount of ejection phase shortening. As LVEDP was increased, there was a parallel decrease in both the amount of isovolumetric lengthening in the ischemic zone and the isovolumetric shortening in the nonischemic area. As a result, acute ischemia produced less of a reduction in ejection phase shortening in the nonischemic area and in stroke volume at high as compared with low LVEDP. We conclude that the ischemic zone imposes a mechanical disadvantage on the nonischemic area, the magnitude of which is directly proportional to the amount of isovolumetric lengthening or bulge in the ischemic zone. An increase in LVEDP during acute ischemia improves regional and global ventricular function by both the Frank-Starling mechanism in the nonischemic (but not the ischemic) area and by reducing the mechanical disadvantage that the ischemic zone imposes on the nonischemic area. PMID- 4042301 TI - Coronary risk factor statement for the American public. A statement of the nutrition committee. PMID- 4042303 TI - Increased lung vasoreactivity in children from Leadville, Colorado, after recovery from high-altitude pulmonary edema. AB - Cardiac catheterization was performed on seven children after recovery from high altitude pulmonary edema. All were life-long residents at elevations above 10,000 feet. Three of the seven had developed pulmonary edema without antecedent travel to low altitude but had an upper respiratory infection. Response of pulmonary arterial pressure to 16% inspired oxygen in all seven was compared with that in six well children who resided at a similar altitude and had no history of high altitude pulmonary edema. With hypoxia the susceptible patients had a greater mean pulmonary arterial pressure (56.3 +/- 23.8) than the nonsusceptible children (18.8 +/- 3.9, p less than .05). Comparison with historical hemodynamic responses in children at high altitudes showed a similar greater mean pulmonary arterial pressure in the susceptible children. Thus, in children from high altitudes, increased pulmonary vasoreactivity to hypoxia may play a role in the pathogenesis of high-altitude pulmonary edema. The development of pulmonary edema in high altitude residents with upper respiratory infections and no antecedent low altitude journey is consistent with the presence of other factors such as inflammation, which may play a role in the pathogenesis of the edema. The finding of right ventricular hypertrophy on an electrocardiogram in children from high altitudes may be predictive of their susceptibility to high-altitude pulmonary edema. PMID- 4042302 TI - Atherogenic lipoproteins and coronary artery disease: concepts derived from recent advances in cellular and molecular biology. PMID- 4042304 TI - Complex ventricular arrhythmias in patients with Q wave versus non-Q wave myocardial infarction. AB - We examined whether or not subsets of patients with complex ventricular arrhythmias after myocardial infarction are at high risk with respect to 1 year mortality after hospital discharge. Based on previous studies showing increased risk for those with non-Q wave infarcts, we hypothesized that complex PVCs (premature ventricular complexes) in this group might be associated with a poorer prognosis than complex PVCs in patients with Q wave infarcts. Seven hundred seventy-seven patients entering our study with acute infarction were followed prospectively for 1 year after undergoing a predischarge 24 hr ambulatory electrocardiographic examination. Patients were classified by electrocardiographic criteria into the following groups: Non-Q wave (n = 191), Q wave anterior (n = 261), and Q wave inferior infarction (n = 325). The following arrhythmias were classified as complex: multiform PVCs, couplets, and ventricular tachycardia. Sixty-two percent of patients with non-Q wave infarcts who did not survive 1 year had complex PVCs, compared with 32% of survivors (p less than .01). No differences were seen in the Q wave subgroup. The survival for patients with Q wave and non-Q wave infarction without complex PVCs were nearly identical at 1 year (93% and 90%), whereas in patients with complex PVCs survival for those with Q wave and non-Q wave infarction was 92% and 76%, respectively (p less than .001). Of those with non-Q wave infarction, only 4% of nonsurvivors were free of any PVCs, as compared with 28% of nonsurvivors in the Q wave group (p less than .02).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4042305 TI - The relationship of white cell count, platelet count, and hematocrit to cigarette smoking in adolescents: the Oslo Youth Study. AB - This article reports on the relationship between cigarette smoking, white blood cell count (WBC), platelet count (PC), and hematocrit in a Norwegian adolescent population. Data were obtained on 439 youths, 14 to 16 years old, as part of the Oslo Youth Study, an investigation of risk factors and behaviors for cardiovascular disease and cancer among adolescents. Analyses of covariance, controlling for height, weight, age, sexual maturation, high-density lipoprotein (HDL) cholesterol, and hematocrit revealed that both male and female regular smokers (those reporting smoking at least once a week) had significantly higher mean WBCs. Male regular smokers also had significantly higher PCs than nonsmokers, and female regular smokers had higher PCs than young women who smoked less often than once a month. Hematocrit, after adjustment for height, weight, age, sexual maturation, and HDL cholesterol, was significantly lower in male regular smokers, while female regular smokers had higher hematocrit values than nonsmokers or occasional smokers. Results of this study show that WBC and PC were increased in adolescents who started smoking relatively recently. This indicates that the increase in white cell count observed in smokers is unlikely to be due to a longstanding smoking-induced chronic disease condition. PMID- 4042306 TI - The nature of opioid involvement in the hemodynamic respiratory and humoral responses to exercise. AB - After 30 min rest in the lying position, 12 healthy male volunteers (average age 22 years) received, in a randomized double-blind cross-over protocol, either saline or naloxone (10 mg iv followed by a continuous infusion of 10 mg/hr). Thereafter they rested for a further 30 min in the recumbent position and for 15 min sitting on a bicycle ergometer; they then exercised to exhaustion. At rest plasma levels of adrenocorticotropin (ACTH), cortisol, and aldosterone increased during infusion of naloxone, while body temperature decreased. During exercise the difference in plasma ACTH between naloxone and saline periods was abolished, while the differences in plasma cortisol and aldosterone lost statistical significance. Intra-arterial pressure, heart rate, ventilation, O2 uptake, and CO2 output were continuously monitored throughout the experiment and were not affected by naloxone. This was also the case for several hormonal and biochemical measurements, including those of plasma renin, angiotensin II, norepinephrine, 13,14-dihydro-15-keto-prostaglandin F2 alpha, glucose and lactate, and serum insulin and growth hormone. Exercise performance was not changed by naloxone. In conclusion (1) during exhaustive graded exercise of short duration opioidergic inhibition of the pituitary-adrenocortical axis is probably not sustained, (2) apart from the latter mechanism, the present study does not support the hypothesis that endogenous opioids are involved in various hemodynamic, respiratory, and hormonal responses to this type of exercise. PMID- 4042308 TI - Sodium hyaluronate (Healon) in cyclodialysis. PMID- 4042307 TI - Effects of reduced left ventricular mass on chamber architecture, load, and function: a study of anorexia nervosa. AB - We investigated the effects of reduction in left ventricular mass on cavity geometry, afterload, pump function, and exercise performance in 17 patients with anorexia nervosa and in 10 age-and sex-matched normal subjects. Left ventricular mass index determined by two-dimensional echo-cardiography was significantly lower than that in normal subjects (53 +/- 15 vs 79 +/- 18 g/m2; p less than .005). Left ventricular end-diastolic and end-systolic volume indexes were also reduced in patients with anorexia nervosa compared with normal subjects (49 +/- 11 vs 65 +/- 17 ml/m2, p less than .005; 14 +/- 5 vs 19 +/- 4 ml/m2, p less than .025). In spite of the reductions in left ventricular mass and volume indexes, left ventricular chamber architecture described as h/R ratio, mass to volume ratio, and short/long left ventricular axis ratio were normal. Left ventricular afterload assessed as end-systolic meridional and circumferential wall stress was normal (59 +/- 18 vs 79 +/- 19 dyne/cm2 X 10(3) and 170 +/- 26 vs 167 +/- 23 dyne/cm2 X 10(3)). Ejection fraction, percent fractional shortening, and the relationship between end-systolic wall stress and ejection fraction were all within normal limits. In seven patients restudied after a 15% to 20% weight gain, left ventricular mass and volume indexes increased significantly but end-systolic wall stress and ejection fraction did not change. Ten patients with anorexia nervosa and resting heart rates and systolic blood pressures significantly lower than control values underwent treadmill testing. Exercise duration, peak heart rate, peak systolic blood pressure, and peak oxygen consumption in these patients were all significantly lower than normal. The hypotensive effect of fasting resulted in an initial decrease in afterload, which was the stimulus for reduction in left ventricular mass. The left ventricular remodeling associated with the mass reduction occurred in such a way that (1) orthogonal, meridional, and circumferential wall stresses were normalized, (2) normal chamber shape and architecture were maintained, and (3) chamber function and stress-shortening relationships were preserved. Thus down-regulation of left ventricular mass per se, like up-regulation of left ventricular mass, is not associated with abnormal left ventricular function. PMID- 4042309 TI - Astigmatic analysis of the scleral pocket incision and closure technique for cataract surgery. PMID- 4042310 TI - Experience in intraocular surgery with the Meditec OPL3 mode-locked and the LASAG Microruptor II Q-switched Nd-YAG lasers. PMID- 4042311 TI - Reproducible measurement of oxygen permeability (Dk) of contact lens materials. PMID- 4042312 TI - An accommodating contact lens. PMID- 4042313 TI - Aging changes in the human lacrimal gland: role of the ducts. PMID- 4042314 TI - Tear film osmolarity and keratoconjunctivitis sicca. PMID- 4042316 TI - Correction of presbyopia with contact lenses and management of posterior capsule after cataract extraction. Adapted from the January 13, 1985 meeting of the Contact Lens Association of Ophthalmologists (CLAO). PMID- 4042315 TI - A CLAO Journal survey of trends in ophthalmology practice. PMID- 4042317 TI - Eleventh International Symposium on Clinical Enzymology 1984--Selected Papers. 15 18 February 1984, Rome, Italy. PMID- 4042318 TI - Preliminary observations on the application of carcino-placental alkaline phosphatase to the investigation of patients with seminoma of the testes. AB - Suitable tumour markers for monitoring the treatment of seminoma of the testis have not yet been established in clinical practice. Carcino-placental alkaline phosphatase (CPAP) has been suggested for this purpose but it is difficult to detect and specifically analyse this enzyme. We have devised an immunoenzymatic method of analysis in which cross-reactions with liver type and intestinal alkaline phosphatase are minimal and we have applied this test to seven patients with histologically proven seminoma. CPAP was raised in 4 patients prior to treatment and chorionic gonadotrophin in two of these. Alpha-fetoprotein was normal in all cases. We conclude that the use of CPAP in monitoring treatment of testicular seminoma is worthy of further attention. PMID- 4042319 TI - Determination of prolinase activity in plasma. Application to liver disease and its relation with prolidase activity. AB - We describe prolinase (EC 3.4.13.8) activity in human plasma for the first time. Optimum activity was obtained with prolylvaline as substrate and 0.02 mmol/L manganese concentration at pH 9.0. Moreover, preincubation with manganese was not required, contrary to prolidase (EC 3.4.13.9) activity. The mean value observed in 106 subjects without liver and renal disorders was 16 U/L +/- 14 (2 SD). We determined this plasma enzyme activity in patients with acute hepatitis and chronic liver disease. Plasma prolinase activity was strongly dependent upon cytolysis because of the high activity in liver and the low activity in plasma. Of 24 patients with chronic liver disease (4 chronic hepatitis and 20 cirrhosis) and without cytolysis, prolinase activity was slightly increased in only three patients, whereas prolidase activity was increased in 13. This could be due to a difference in the activation of these two enzymes in liver during the fibrotic process. PMID- 4042320 TI - Fecal chymotrypsin: a new diagnostic test for exocrine pancreatic insufficiency in children with cystic fibrosis. AB - The purpose of this report is to evaluate whether a new, simple, non-invasive method for chymotrypsin measurement in stools is useful for the diagnosis of exocrine pancreatic insufficiency in cystic fibrosis (CF). A hundred children aged from 2 months to 12 years were tested: 50 children had been admitted for chronic diarrhoea, 15 for cystic fibrosis and 40 acted as controls. Chymotrypsin in stools was assayed using a kinetic measurement with Succ-Ala-Ala-Pro-Phe-pNa as substrate in a simple photometric assay. In 13 of 15 children with cystic fibrosis, stool enzyme levels were always remarkably low, while all control subjects and all children not presenting cystic fibrosis had normal stool levels of chymotrypsin. Our data suggest that stool chymotrypsin measurement is a simple and reliable "tubeless" test for the evaluation of exocrine pancreatic insufficiency in children with cystic fibrosis. PMID- 4042321 TI - Macro creatine kinase type 2: a marker of myocardial damage in infants? AB - The case histories of two children (aged two months) affected by myocarditis showing an atypical band of serum creatine kinase (EC 2.7.3.2; CK) in the CK isoenzyme electrophoretic pattern are reported. The electrophoretic mobility on cellulose acetate of the atypical iso-CK band and its greater relative molecular mass, the lack of binding with immunoglobulins and the result of CK-BB determination by RIA, allowed us to identify the band with an oligomeric form of the mitochondrial isoenzyme. One child died 2 days after admission, while in the other it was possible to demonstrate reduction and disappearance of the atypical band in concomitance with a marked clinical improvement. Our findings suggest that the oligomeric form of mitochondrial-CK is released in conditions of serious heart muscle damage, and that it may be an indicator of myocardial cellular necrosis in pediatric patients. PMID- 4042322 TI - Inhibition of uricase by pyrimidine and purine drugs. AB - A number of barbiturates inhibit uricase from porcine liver competitively, the Ki, values being in the range 1 to 13 X 10(-3) mol/L. In general the Ki increases as the size of the substituents at C-5 increases. Theophylline also inhibits the enzyme competitively (Ki = 1 X 10(-3) mol/L) but theobromine and caffeine have no inhibitory action at 0.01 mol/L. A number of sulphonamides and some other heterocyclic compounds, at 10(-3) mol/L, do not inhibit uricase. The possible effects of such inhibition in clinical assays for plasma/serum urate are discussed but it is concluded that the compounds which were studied are unlikely to cause significant interference in the assay. PMID- 4042323 TI - On the difference between colonic and small intestinal alkaline phosphatase. AB - Colonic and small intestinal alkaline phosphatase extracts were studied biochemically and electrophoretically to elucidate the source of a reported difference in cellulose acetate electrophoretic mobility. Both preparations were inactivated with 0.5 mmol/L L-phenylalanine but retained full activity in the presence of 1.0 mmol/L tetramisole. Treatment with neuraminidase changed a minor fraction of the small intestinal but the major portion of the colonic alkaline phosphatase to a cathodically migrating form. The most likely explanation for our findings is that the colon and small intestinal alkaline phosphatase are mixtures of the same multiple forms but in different proportions. PMID- 4042324 TI - Preparation and certification of human hair powder reference material. AB - Human hair powder reference material was prepared and certified for elemental composition. Human scalp hair (from Japanese men) was washed in a non-ionic detergent solution in an ultrasonic cleaner, dried, ground in an agate ball mill, sieved through a polyethylene net, blended, bottled (1100 vials, 2 g each), and finally sterilized by 60Co radiation. The prepared material satisfied the homogeneity criteria for a reference material. We determined trace elements by inductively coupled plasma atomic emission spectrometry and atomic absorption spectrometry and investigated matrix interference effects. The material was certified by using the data obtained by various analytical techniques; certified values are provided for Ca, Cd, Cr, Cu, Fe, Hg, K, Mg, Mn, Na, Ni, Sr, and Zn. The elemental composition of this reference material is considered similar to normal values for the male Japanese population. PMID- 4042325 TI - Analysis for nicotine and cotinine in hair to determine cigarette smoker status. AB - Noninvasive validation of cigarette smoking behavior is necessary for large population studies, especially with adolescents, where peer pressures can compromise self-report. Saliva and urine samples provide biological material for confirmation of recent nicotine intake by analysis for cotinine, the major metabolite of nicotine. However, detection of infrequent use of cigarettes can be missed in a single annual screen when participants have not smoked in the preceding week. We analyzed scalp hair from smokers and controls, to see whether hair could provide reliable samples for determining nicotine uptake. The amounts of nicotine and cotinine we detected in these samples correlated with individual smoking habits and exposures. PMID- 4042326 TI - Peroxidase-coupled method for kinetic colorimetry of total creatine kinase activity in serum. AB - We describe a peroxidase-coupled method involving a colorimetric indicator reaction for determining the total activity of creatine kinase (EC 2.7.3.2) in serum. The kinetically favorable reverse reaction is exploited to generate adenosine 5'-triphosphate, which is used in the glycerol kinase-catalyzed phosphorylation of glycerol. The glycerol 3-phosphate so generated is oxidized in the presence of alpha-glycerophosphate oxidase to produce hydrogen peroxide, which is reduced in the presence of peroxidase with the simultaneous oxidation and coupling of 4-aminoantipyrene and 2-hydroxy-3,5-dichlorobenzenesulfonate to produce an intensely colored red chromogen. Results of the proposed method (y) correlate well with those of the Boehringer-Mannheim "CK-NAC UV" method as applied to the Hitachi 705 chemistry analyzer (y = 1.025 chi - 18.1, r = 0.9985, n = 100, range = 19-4531 U/L). The sensitivity of the method, based on molar absorptivities, is nearly fourfold that of procedures involving the reduction of NADP+. PMID- 4042327 TI - Changes in the ratio of lactate dehydrogenase isoenzymes 1 and 2 during the first day after acute myocardial infarction. AB - It is known that the ratio of isoenzyme 1 to total lactate dehydrogenase (LD, EC 1.1.1.27) in serum is increased in all patients with acute myocardial infarction within 24 h of the infarct. We now show that the LD-1/LD-2 ratio for serum more promptly indicates acute myocardial infarction, being for most patients equivalent to measurement of creatine kinase (EC 2.7.3.2) isoenzyme 2 (CK-2, CK MB) in serum. Of 128 patients with a confirmed diagnosis of myocardial infarction, 66 had normal values for all "cardiac" enzymes at the time of admission, but greater than 75% of them showed a parallel increase in values for CK-2 and the LD-1/LD-2 ratio. Of the 26 patients who had one or more abnormal values for cardiac enzymes on admission, 95% showed a parallel increase in CK-2 and the LD-1/LD-2 ratio, the median time for the beginning of these changes being 9 h from the onset of chest pain. The remaining 36 patients were excluded from the study because CK-2 decreased after admission or because the time of onset of chest pain was uncertain. PMID- 4042329 TI - Identification by nuclear magnetic resonance and mass spectrometry of a glucuronic acid conjugate of o-hydroxybenzoic acid in normal urine and uremic plasma. AB - An endogenous compound (included in the fraction of uremic toxins often called the "uremic middle molecules") was separated from plasma of uremic patients and urine from normal persons. As elucidated by mass spectrometry, enzymatic hydrolysis, and 1H, 13C nuclear magnetic resonance, it appears to be a conjugate of o-hydroxybenzoic acid with glucuronic acid. Its presence in urine of healthy subjects indicates its physiological character. PMID- 4042328 TI - Lack of specificity of current anti-digoxin antibodies, and preparation of a new, specific polyclonal antibody that recognizes the carbohydrate moiety of digoxin. AB - Current immunoassays for digoxin do not distinguish digoxin from its glycosidic metabolites. We have synthesized a novel digoxin/bovine serum albumin conjugate via reductive ozonolysis of the lactone ring such that the carbohydrate moiety of digoxin remains intact. Antibodies raised against this conjugate show minimal cross reactivity to digoxigenin, bisdigitoxide, monodigitoxide, digoxigenin, and digitoxin. With this antibody, digoxin can be measured in the presence of these metabolites. PMID- 4042330 TI - Oxygen toxicity related to exposure to lead. AB - We evaluated superoxide dismutase (EC 1.15.1.1) and glutathione peroxidase (EC 1.11.1.9) activities in the erythrocytes of lead-exposed and nonexposed workers from distinct industries localized in the State of Sao Paulo, Brazil. Concentrations of either lead or protoporphyrin IX, or both, in blood were used to indicate the extent of exposure. In all cases, values for superoxide dismutase were significantly higher in the exposed workers. The dose-response relationship between this enzyme and lead concentrations was roughly linear for the workers with greater than 40 micrograms of lead per 100 g of blood. Except for the sample from one of the industries, the corresponding glutathione peroxidase activities were also significantly higher in lead-exposed workers. These data, together with those previously found for patients with intermittent acute porphyria, suggest that in both groups the accumulation of heme precursors is connected to the exacerbated production of activated oxygen species. PMID- 4042331 TI - Chemical nature of a synthetic bilirubin conjugate and its reactivities in the total and direct reactions by the Jendrassik-Grof method. AB - Using liquid chromatography, nuclear magnetic resonance spectroscopy, and elemental analyses, we verified that a commercially available synthetic bilirubin conjugate is predominantly a ditaurobilirubin (DTB) disodium salt. The Jendrassik Grof total bilirubin (TBIL) method quantitatively measures unconjugated bilirubin (Bu) and the Bu-equivalent content in DTB, from which we infer that the azopigments of Bu and DTB have identical molar absorptivities, which do not change in the presence of either serum or serum albumin of human or bovine origin. However, based on the ratio of direct bilirubin (DBIL) to TBIL, the DBIL reaction in dilute HCI is incomplete (even up to 20 min), with lower yields in a matrix of bovine serum albumin than in human serum. By contrast, the DBIL reaction in acetate buffer (pH 4.75) is quantitative for DTB in human serum (or its albumin), but less so in bovine serum (or its albumin). DTB is water soluble, is relatively stable when lyophilized with human serum, and is determined with such high precision in the above-mentioned endpoint assays that it may be a suitable surrogate calibrator for conjugated bilirubin. PMID- 4042332 TI - Improved assay of antithrombin-III. Effects of certain additives on thrombin and on chromogenic peptide substrates. AB - When manual assays of antithrombin-III with use of different synthetic chromogenic peptide substrates are modified for a centrifugal analyzer, the downward deflection of the reference curve at the zero point raises a serious problem, because the position of the zero value is included in the calculation of the reference curve. Complete linearity was obtained by addition of polyethylene glycol 6000 to the thrombin solution and Tween 80 to the substrate solution in final concentrations of 1 g/L and 100 mg/L, respectively. The additives increased the concentration of active thrombin in the solutions by preventing its adsorption and aggregation, and the solubility of the substrates in aqueous media is increased. The precision of the optimized method, tested in routine assays during three months, yielded an estimated day-to-day CV of 3.4%. PMID- 4042333 TI - Liquid chromatography of free hydroxyproline in serum. AB - We report a "high-performance" liquid-chromatographic method for measuring free hydroxyproline in serum. After separating the free hydroxyproline from the protein- and peptide-bound forms by centrifugal ultrafiltration, we derivatize the free form with 4-dimethylaminoazobenzene-4'-sulfonyl ("dabsyl") chloride and separate and quantify the derivative on a C18 chromatographic column. The mobile phase is sodium acetate buffer and acetonitrile, in a multilinear solvent gradient. The derivative is detected at 436 nm. Mean analytical recovery was 73%. The assay curve is linear from 14 to 213 pmol of hydroxyproline per 5-microL injection. The within- and interassay CVs were 8% at 10.7 mumol/L hydroxyproline and 10% at 13.5 mumol/L hydroxyproline, respectively. PMID- 4042334 TI - Anion-exchange chromatography to determine the concentration of chloride in sweat for diagnosis of cystic fibrosis. AB - For the diagnosis of cystic fibrosis, we use the "Macroduct Sweat Collection System" (Wescor) to sample sweat, and anion-exchange chromatography to determine its chloride content. The chromatographic system consists of a Whatman Partisil SAX 10-microns column, an isocratic phosphate-buffered mobile phase, and ultraviolet detection at 200 nm. The sweat chloride concentrations of 10 individuals with cystic fibrosis ranged from 101 to 131 mmol/L (mean 111, SD 9 mmol/L). For 11 controls the values ranged from 13 to 54 mmol/L (mean 28, SD 11 mmol/L). We conclude that the procedure is reliable for the diagnosis of cystic fibrosis. PMID- 4042335 TI - Solid-phase extraction and liquid chromatography for improved assay of cyclosporine in whole blood or plasma. AB - In this simple, precise, accurate, and specific isocratic liquid chromatographic procedure for determining cyclosporine, the cyclosporine is extracted from 1 mL of whole blood or from plasma, with 500 micrograms of cyclosporin D added per liter as internal standard, by elution from a Bond-ElutTM C18 extraction column with 300 microL of a mixture of ethanol and tetrahydrofuran. A 100-microL aliquot of the eluate, injected onto a cyano-phase analytical column, is eluted with a mixture of acetonitrile and pH 7.0 phosphate buffer at a flow rate of 1.0 mL/min and at 50 degrees C. Detection is at 210 nm. The chromatography is complete in less than 14.0 min. The method can measure less than 10.0 micrograms/L. Analytical recovery of cyclosporine added to whole blood ranged from 99 to 109% for concentrations up to 2000 micrograms/L. Between-run CVs ranged from 6.4 to 6.6%. None of numerous drugs and steroids tested interfered. Results by radioimmunoassay exceeded by 20 to 350% those measured by the present method. PMID- 4042336 TI - Studies directed toward labeling analysis of angiotensin II in plasma. AB - We assay a 1-mL plasma sample containing angiotensin II (103 pg by radioimmunoassay) for the hormone by the following sequence of steps: add 125I labeled val5-angiotensin II as an internal standard, extract on a C18 Sep Pak column, extract on an antibody affinity column, label the extract with an 125I Bolton-Hunter reagent, separate on a Bio Gel P2 column, and repetitively separate on a reversed-phase "high-performance" liquid-chromatographic column, detecting the eluting compounds by counting radioactivity. The fact that we measured 46 pg of angiotensin II-like substance per milliliter in a sample of pooled plasma is encouraging for the further development of this methodology. In particular, replacing the radioisotope with a more suitable chemical label such as an electrophoric (electron-capturing) release tag should be useful. PMID- 4042337 TI - Five methods for measuring low-density lipoprotein cholesterol concentration in serum compared. AB - Five methods for the quantification of low-density-lipoprotein cholesterol were compared: ultracentrifugation, electrophoresis, precipitation with polyvinyl sulfate or heparin, and an indirect calculation procedure (Friedewald formula). Excellent agreement of results was obtained with all procedures for 49 of 51 sera. Discrepancies were as much as 1.69 g/L for the remaining two cases, which contained appreciable amounts of "floating" beta-cholesterol as detected with a combination of ultracentrifugation and electrophoresis. PMID- 4042338 TI - Increased activity of creatine kinase isoenzyme MB in a theophylline-intoxicated patient. AB - A 78-year-old woman had increased activities of creatine kinase (CK; EC 2.7.3.2) and CK-MB isoenzyme in her serum, associated with severe theophylline intoxication. The time course for CK-MB activity was similar to that from an acute myocardial infarction. Clinical findings, however, including electrocardiograms, did not support the diagnosis of myocardial infarction. We suggest caution in interpreting CK-MB results in severe theophylline intoxication. PMID- 4042339 TI - Radioimmunoassay of human choriogonadotropin. PMID- 4042340 TI - Estimation of low-density lipoprotein by the Friedewald formula and by electrophoresis compared. PMID- 4042341 TI - Prolactin concentrations in serum unchanged in transient global amnesia. PMID- 4042342 TI - Serum fructosamine and assay pH. PMID- 4042343 TI - Low thyrotropin concentrations as measured with a commercial kit. PMID- 4042344 TI - Salicylate procedure for the Cobas-Bio analyzer. PMID- 4042345 TI - Calibration of direct ion-selective electrodes for plasma Na+ to allow for the influence of protein concentration. PMID- 4042346 TI - A case of barbital poisoning. PMID- 4042347 TI - Total protein concentrations determined for CAP urine survey specimens with Coomassie Brilliant Blue reagent are dilution dependent. PMID- 4042348 TI - Prognostic significance of creatine kinase MB isoenzyme in serum of patients with renal failure. PMID- 4042349 TI - Using filtrates of urine centrifuged through a microconcentrator membrane to distinguish false and true positives for protein by sulfosalicylic acid precipitation. PMID- 4042350 TI - Recurrent infections in sickle cell disease: haematological and immune studies. AB - Some haematological and immunological indices were compared in 19 children with sickle cell disease and a history of recurrent infections and in 16 children with sickle cell disease without any known infections. The recurrent infection group had significantly greater pitted red cell counts and greater absolute monocyte counts. No differences were apparent in routine haematological indices, foetal haemoglobin, immunoglobulin, or complement levels between the groups. The interpretation of these results is discussed. PMID- 4042351 TI - Lack of effect of increased 2,3-diphosphoglycerate on flux through the oxidative pathway in phosphoglycerate kinase deficiency. AB - Erythrocyte enzyme and substrate levels in two subjects with phosphoglycerate kinase deficiency are reported. The effect of the increased 2,3 diphosphoglycerate, which has been reported as an inhibitor of 6-phosphogluconate dehydrogenase, on the flux through the pentose phosphate pathway, was assessed. There was no significant difference in the flux through erythrocytes from one of the affected subjects and normal subjects in the presence and absence of methylene blue. PMID- 4042353 TI - Anion-exchange high performance liquid chromatography method for the quantitation of nucleotides in human blood cells. AB - An anion-exchange high performance liquid chromatography (HPLC) method is described for the quantitation of intracellular purine and pyrimidine nucleotides. With an ammonium phosphate salt and pH gradient, complete separation is achieved of all major nucleotides and several interfering substances, such as dehydroascorbic acid and NAD. For optimal resolution of the monophosphates, strict control of the equilibration pH is essential. To prevent interference by a degradation product of NADPH with the determination of GDP, the pH of the high ionic strength buffer has to be in the range of 4.9-5.0. The use of radially compressed, prepacked cartridges filled with Partisil-10 SAX appeared to be a fast and cheap alternative for expensive stainless-steel columns. The use of ammonium phosphate buffers, in combination with precolumns filled with pellicular silica and SAX resin, and interim EDTA washes prevents baseline shift. This allows analysis at 0.01 Absorbance Units Full Scale during the entire column lifetime (about 180 analyses), which is sufficiently sensitive for the quantitation of low levels of nucleotides, especially when the amount of sample is limited. The usefulness of the presented chromatographic system is demonstrated by the quantitation of the nucleotides in extracts of lymphocytes and neutrophils from the blood of healthy human donors. With this method nucleotide concentrations were measured, with a within-assay variation of 5-10% and an inter-donor variation of 10%. PMID- 4042352 TI - Accurate quantitation of native Gc in serum and estimation of endogenous Gc: G actin complexes by rocket immunoelectrophoresis. AB - Complex formation between purified Gc and G-actin caused increased rocket height on immunoelectrophoresis with monospecific Gc antiserum, and artifactually high calculated Gc levels. The increase in rocket height varied in log: linear fashion with the amount of G-actin present, up to a plateau attained at equimolarity. The raw Gc values could therefore be corrected to within +/- 10% of known levels by addition of excess G-actin and use of standard plots obtained with Gc after saturation with G-actin. This also allowed quantitation of the percentage of Gc complexed with G-actin. In subsequent studies of whole human sera, comparison of normal controls with pregnant subjects and patients with liver disease showed evidence of differences both in absolute quantities of Gc and the relative proportion circulating as complex with G-actin. This appeared to be due to increased release of cellular actin into the extracellular space. These results show that rocket immunoelectrophoresis can be modified to provide accurate Gc levels, and also information concerning different molecular forms of this protein. PMID- 4042354 TI - Indices for the age of the creatine kinase M-chain in the blood. AB - The apparent activation energy of the CK reaction as well as the Michaelis-Menten constants and the isoelectric point of CK MM can be used as indices for the mean age of the CK M-chain in the blood in vivo and in vitro. Modifications in the CK M-chain take place in vivo in the blood and in vitro in a serum matrix. Gradual increases in the apparent activation energy are also observed both in vivo and in vitro. It is confirmed that the modification in the CK M-chain causes a rise in the apparent activation energy, mu. A gradual increase in apparent activation energy, due to the ageing process of the CK M-chain, was observed after myocardial infarction. A significantly increased value for u was observed at the time that total CK activity already had returned to reference values. In spite of the normal CK value, the apparent activation energy still indicated that there had been myocardial damage. The Michaelis-Menten constants for creatine phosphate and ADP are also influenced significantly by the modification in the M-chain. While the apparent activation energy increases, the Michaelis constants decrease in the order MM3, MM2, MM1. The Michaelis-Menten constants for both ADP and CrP can be used as an index for the mean age of the enzyme in the blood. The Michaelis-Menten constants for CrP and ADP show significant variations with the measuring temperature for virtually all CK MM forms. PMID- 4042355 TI - Variations in HDL and VLDL levels chronic alcoholics. Influence of the degree of liver damage and of withdrawal of alcohol. AB - Changes in plasma HDL and VLDL levels were investigated in 284 chronic alcoholics staying in a Detoxification Centre where they initiated or continued abstinence. The data show that the variations in plasma HDL are modulated by the degree of liver injury. In severe hepatic damage HDL levels are sharply decreased. An alcohol-induced rise in HDL can occur in the only subjects with no signs of hepatic insufficiency. This elevation is rapidly reversible after withdrawal of alcohol. Such a rise might reflect enhanced synthesis and release by liver but might also be due to an accelerated turnover of the VLDL. PMID- 4042356 TI - The value of combined determination of high molecular mass API and LP-X in the differential diagnosis of intrahepatic and extrahepatic obstruction. AB - Combined determination of serum lipoprotein-X and electrophoretic separation of high molecular mass (HMr) alkaline phosphatase has been proposed as a marker for the differential diagnosis between intrahepatic cholestasis and extrahepatic obstructive jaundice. Of 32 patients who were known to be lipoprotein-X positive and in whom a definitive diagnosis had been made, 13 had intrahepatic cholestasis and 17 extrahepatic obstruction, and 2 had both intrahepatic and extrahepatic obstruction. The detection of HMr alkaline phosphatase isoenzyme proved to be a sensitive and specific test for detecting liver disease, particularly obstructive liver disease. The diagnostic significance of the combined determination of serum lipoprotein-X to demonstrate or exclude cholestasis and electrophoretic separation of HMr alkaline phosphatase isoenzymes to allow differentiation between intrahepatic cholestasis and extrahepatic obstruction was investigated. PMID- 4042357 TI - Significance of vitamin A and retinol binding protein serum levels after burn injury. PMID- 4042358 TI - Stability of amino acids in human plasma. PMID- 4042359 TI - A rapid, simple and sensitive gas chromatographic micromethod for the quantitation of butyric acid and other short-chain fatty acids in serum. PMID- 4042360 TI - Adenine phosphoribosyl transferase: assay using high performance liquid chromatography. PMID- 4042361 TI - Cell density affects prolidase and prolinase activity and intracellular amino acid levels in cultured human cells. AB - Prolidase (EC 3.4.13.9) and prolinase (EC 3.4.13.8) and intracellular amino acid levels in cultured human cells increased when cell density rose. Firstly, two normal fibroblast strains were continuously cultured for 21 days and these parameters were measured on days 3, 7, 10, 14, 17 and 21 after plating. Prolidase, prolinase and amino acid levels varied considerably depending on the duration of culture and growth rate. Secondly, we studied the action of different cadmium and cobalt concentrations on prolidase activity. These two effectors altered this enzyme activity, but secondarily to modifying cell density. Thirdly, prolidase activity was investigated in 8 control amniotic cell strains, with a view to prenatal diagnosis of inherited prolidase deficiency, and we noted the same cell density interference. Due to the large variations related to cell density, we recommend specifying the number of cells per unit surface, and avoiding the term 'cells at confluency' which is unduly vague. PMID- 4042362 TI - Determination of copper in whole blood, plasma and serum using Zeeman effect atomic absorption spectroscopy. AB - Methods are presented for the determination of copper in whole blood, plasma and serum using Zeeman effect flame and furnace atomic absorption spectroscopy. Three flame measurement modes were compared: continuous aspiration, microsampling in the peak height mode and microsampling in the peak area mode. The microsampler/peak area method was the most satisfactory. The precision for the microsampler/peak area method was as follows: the within-run relative standard deviation (RSD) was 1.84% and 1.89% for whole blood specimens with copper concentrations of 983 micrograms/l and 974 micrograms/l, respectively. The within run RSD was 2.14, 1.66 and 0.87% for plasma specimens with concentrations of 990, 1,467 and 1,963 micrograms/l, respectively. Within-run RSD was 6.64, 2.86 and 1.15% for serum specimens with concentrations of 462, 984 and 2,056 micrograms/l, respectively. The average detection limit for the microsampler/peak area method was 10.3 micrograms/l. Concentrations could be read directly from standards prepared in human whole blood, plasma or serum pools or in a commercial control. PMID- 4042363 TI - Sensitive determination of urinary vanadium by solvent extraction and atomic absorption spectroscopy. PMID- 4042364 TI - Interference of labetalol metabolites in the determination of plasma catecholamines by HPLC with electrochemical detection. AB - The alpha and beta adrenoceptor blocking drug labetalol is a potent antihypertensive agent in widespread clinical use. Its interference in the classical chemical estimations of urinary catecholamines and their metabolites has been the subject of several reports. Factitiously raised values have been noted in both the fluorimetric catecholamine assay, and the standard spectrophotometric procedure for total (free and conjugated) metadrenalines. To avoid such drug interference, modification of these methods is required in the estimation of catecholamines and their o-methylated metabolites. Alternatively, VMA estimations or plasma/urinary catecholamine measurements by radioenzymatic assay may be used in patients on labetalol. Although high performance liquid chromatography coupled with electrochemical detection (HPLC-ECD) methods for estimation of plasma catecholamines are now in widespread use, the interference of labetalol in this method has not been reported. We now report that significant direct interference of labetalol in the HPLC-ECD assay does indeed occur, and can yield spuriously raised adrenaline levels. PMID- 4042365 TI - The quantification of human IgG subclasses in reference preparations. AB - Three laboratories took part in an investigation about the possibilities of quantitative determination of IgG subclasses. Polyclonal monospecific antisera were used in combination with different kinds of calibrators to assess the IgG subclass levels in three W.H.O. reference preparations. IgG 1 could be determined with satisfactory precision; for the other subclasses the quantification was less precise. The precision was dependent on the antisera for IgG 1, IgG 2 and IgG 4 but mainly on the calibrators for IgG 3. Mass units are to be preferred to relative units. W.H.O. reference preparation 67/97 is proposed as a reference for determination of IgG subclasses in mass units. The target values are 5.0 g/l for IgG 1, 2.6 g/l for IgG 2, 0.4 g/l for IgG 3 and 0.5 g/l for IgG 4. These values add up to a total IgG value close to earlier W.H.O. estimates. PMID- 4042366 TI - Semi-micro method for the determination of cation flux rate constants in erythrocytes. PMID- 4042367 TI - The tubular maximum for calcium reabsorption: normal range and correction for sodium excretion. AB - Increased tubular reabsorption of calcium is one of the three variables which can contribute to the pathogenesis of hypercalcaemia. It is therefore important to establish the normal range for this variable in a manner which allows for its variation with the plasma calcium concentration. Graphic methods depicting the relationship between urinary calcium excretion and plasma calcium concentration are valid but cumbersome and imprecise. The notional tubular maximum for calcium reabsorption (TmCa) has therefore been calculated in 130 healthy young subjects and a normal range of 1.75-2.61 mmol/l of glomerular filtrate established. Owing to the dependence of urinary calcium on urinary sodium, TmCa was negatively related to sodium excretion. Because the latter was higher in the males than the females, mean TmCa was slightly (but not significantly) lower in our male than our female subjects. The normal range of TmCa, corrected to zero sodium excretion, is 1.98-2.76 mmol/l of glomerular filtrate. The TmCa was also calculated using plasma calcium values corrected for albumin concentration. The range of TmCa using both corrections is 1.98-2.71 mmol/l of glomerular filtrate. PMID- 4042368 TI - Comparison of enzymatic characteristics of creatine kinase BB from human healthy and tumor stomach tissues. AB - Creatine kinase (ATP: creatine N-phosphotransferase, EC 2.7.3.2, CK) BB isoenzyme from stomach tumor tissue was partially purified and its characteristics were compared with those from healthy tissue. Molecular mass of tumor CK-BB was estimated to be 82 000 by polyacrylamide gel electrophoresis. Tumor CK-BB was separated into 2 main subbands around pH 4.5 and 11, minor subbands around pH 5 7.5 by agarose isoelectric focusing. The isoenzyme reacted with anti-human brain CK-BB antibodies and formed a hybrid, CK-MB, with CK-MM prepared from healthy human skeletal muscle. The above physicochemical and immunological characteristics of tumor CK-BB were the same as those of normal CK-BB from normal stomach tissue. Optimum pH of tumor CK-BB was more acidic than that of normal CK BB. Affinity for creatine phosphate and heat sensitivity of tumor CK-BB were slightly lower than those of normal CK-BB. Tumor CK-BB was more stable after iodoacetamide and urea treatments. PMID- 4042369 TI - Salivary cortisol for the evaluation of Cushing's syndrome. AB - Cortisol concentrations were measured in matched plasma and salivary samples from 8 healthy controls, 8 patients with Cushing's syndrome and 4 patients suspected of having spontaneous hypercortisolism. In healthy subjects, the circadian rhythm in salivary cortisol paralleled that in plasma. Absence of the diurnal rhythm in Cushing's syndrome was seen in saliva as well as in plasma. After ACTH stimulation, mean peak cortisol in saliva showed a 3-fold increase while in plasma there was a 2.5-fold increment above baseline. Cushing's syndrome, due to pituitary or adrenal adenoma was diagnosed equally well by measuring the cortisol response to cosyntropin in either plasma or saliva. Finally, the low- and high dose dexamethasone suppression test was reflected equally well in both plasma and saliva. In patients suspected of having Cushing's syndrome dynamic tests can be performed in both plasma and saliva. However, in some samples, the salivary cortisol measurement appears advantageous over plasma cortisol determination. PMID- 4042370 TI - The role of urea in albumin dimerisation in nephrotic urines. AB - Albumin dimerisation in nephrotic urine frozen to -20 degrees C occurs at low ionic strength in the presence of quite low concentrations of urea (greater than 0.2 mol/l). Urea will also dimerize normal serum albumin under these conditions. The appearance of dimer in patients with a nephrotic syndrome treated with steroids is significantly correlated (p less than 0.001) with an increase in urinary urea concentration. PMID- 4042371 TI - Serum and interstitial fluid apolipoprotein E levels in the healthy and in hyperlipoproteinemia type III as studied by radioimmunoassay. AB - In order to study the relationships between serum lipoprotein lipid concentrations and the concentrations of apo E in serum and interstitial fluid, we have developed a specific, sensitive and rapid radioimmunoassay for this apolipoprotein. Studies of the interstitial fluid lipoproteins and of the gradient between the lipoprotein concentrations in interstitial fluid and serum may add to our understanding of the development of atherosclerosis and xanthomatosis. Serum, interstitial fluid, lipoproteins or standards were incubated with 125I-labelled apo E and rabbit antiserum against apo E for 90-120 min at room temperature. The immune complexes were harvested with the use of formalin-treated staphylococci. The displacement curves produced by standard and samples of serum, interstitial fluid and isolated lipoproteins were linear in logit-log plots and had identical slopes. Delipidation did not change the results and the recovery of added apo E to a serum sample was 96 +/- 5% (n = 5). Apo E was found in all major lipoprotein classes and the concentrations of apo E in serum and in interstitial fluid were 36 +/- 19 mg/l and 8 +/- 4 mg/l, respectively, in normals (n = 21) and 305 +/- 125 mg/ml and 20 +/- 9 mg/l, respectively, in patients with HLP type III (n = 11). Highly significant positive correlations were found in HLP type III between the interstitial fluid level of apo E and the corresponding concentrations of cholesterol and triglyceride. Interstitial fluid apo E concentrations were significantly correlated to apo E but not to the lipid levels in serum, indicating that only some subclasses of the serum lipoproteins are transported to the interstitial compartment. PMID- 4042372 TI - Colorimetric measurement of serum magnesium with an IL micro centrifugal analyzer. PMID- 4042373 TI - A quantitative IgE radioimmunoassay in dried blood spots suitable for neonatal screening of atopy. PMID- 4042374 TI - Serum bile acid composition in patients with cystic fibrosis. AB - Serum bile acid composition was examined in detail using capillary column gas chromatography and mass spectrometry in 10 children with cystic fibrosis (CF) and 4 healthy children. The mean total bile acid concentration in fasting serum of CF patients was 2.33 +/- 0.84 mumol/l, slightly lower than but not statistically significantly different from healthy controls (mean 2.86 +/- 0.98 mumol/l) and appeared to show no relationship to the degree of exocrine pancreatic insufficiency. Analysis of individual serum bile acids in these children showed that cholic acid represented less than 10% of the total bile acids. Chenodeoxycholic acid was the predominant serum bile acid; the mean concentration in CF patients was 0.98 +/- 0.51 mumol/l, lower than for the healthy controls (1.69 +/- 0.84 mumol/l). Concentrations of lithocholic acid, 3 beta-hydroxy-5 cholenoic, ursodeoxycholic and 3 beta, 7 alpha, 12 alpha-trihydroxy-5 beta cholanoic acids in fasting serum samples of the CF patients were not significantly different from the healthy control sera but were higher than those normally found in adults. Measurements of fecal bile acid excretion indicated an increased loss of primary bile acids in patients with CF consistent with an impairment of the enterohepatic circulation of bile acids. PMID- 4042375 TI - Release patterns of CK-MB and mitochondrial CK following myocardial ischaemia. AB - Following myocardial damage as in acute myocardial infarction (AMI) or open heart surgery, the tissue damage might result in a release of mitochondrial CK (CK MIT). The presence of this CK isoenzyme in serum may be detected after chromatographic separation of CK-activity on Sephacryl S-200. By combining chromatographic separation of CK-MB with immunologic inhibition of CK-M, both CK MB and CK-MIT can be estimated in serum. Using this procedure changes in enzyme activities were studied in ten patients with AMI and twelve patients subjected to open heart surgery using cardioplegia. Following AMI CK-MB peaked about 24 h after onset of ischaemic symptoms. CK-MIT increased similarly and reached a plateau after 24 h where it remained during an additional 24-36 h. At peak CK-MB concentration, the corresponding CK-MIT activity was about 22% of the CK-MB activity. Following cardiac surgery there was a rapid release of CK-MB with a peak about 5 h after release of aortic cross-clamping, and with a simultaneous CK MIT activity amounting to 19% of the CK-MB activity. In conclusion, CK-MIT is released into serum following myocardial ischaemia. Its appearance has time characteristics similar to that of other mitochondrial enzymes. The CK-B method does not specifically determine CK-B, but non-CK-M, which in cardiac ischaemia at peak serum CK-MB concentrations includes about 20% CK-MIT. PMID- 4042376 TI - Heterogeneity of 125I-labeled human thyroglobulin preparations. AB - This study was undertaken to evaluate the heterogeneity and stability of 125I labeled human thyroglobulin (Tg) tracers. Tg, labeled with 125I by either a Chloramine T (CT) or a Glucose Oxidase/Lactoperoxidase (GO) method, showed considerable heterogeneity of labeled components, the relative proportions of which were a function of the Tg preparation and the iodination method used. The four largest components had apparent molecular weights as follows: A = 1 200 000 Da; B = 670 000 Da; C = 530 000 Da and D = 290 000 Da. Both B and C were immunoactive. B was considered to be 19S Tg. A non-specific binding difference, (NSB delta) between nonhuman matrices used for diluting standards and human sera was found for the partly immunoactive aggregate component A, (5-20%) and the nonimmunoactive component D, (20-50%), but was minimally present for components B and C (less than 5%). The [125I]19S Tg(B), stored at -70 degrees C, showed rapid spontaneous decomposition with time (50% lost by 8 days), with generation of C, D and iodide. The loss of B was related to specific activity and was least in GO labels. 125I labeling of Tg by GO produced tracers with better immunoactivity, stability and lower NSB delta than comparative CT tracers. Definitive purification and repurification of [125I]Tg tracers before use is necessary in order to remove degradation products with the potential to compromise the accuracy and specificity of serum Tg radioimmunoassay (RIA) measurement. PMID- 4042377 TI - Erythrocyte malondialdehyde release in vitro: a functional measure of vitamin E status. AB - The definition for a sufficient vitamin E level has often been based on population studies that established the normal range of values for fasting plasma or serum vitamin E and more recently for vitamin E to total lipid ratios. These endpoints for vitamin E replacement strategies may not be readily achievable, particularly in the cholestatic patient for whom it is often impossible to reach and sustain normal levels even with massive doses of vitamin E. Vitamin E is believed to function as an antioxidant in vivo protecting membranes from lipid peroxidation. Malondialdehyde (MDA), a product of polyunsaturated fat peroxidation, was measured as the thiobarbiturate derivative in the supernatant following incubation of erythrocytes in hydrogen peroxide. The two different incubation conditions described here and the subsequent measurement of MDA appear to provide a sensitive functional assessment of vitamin E status. The clinical utility of this assay, which requires just 1.5 to 2.0 ml of whole blood, was demonstrated by comparing the percent of total MDA released from individuals regarded as vitamin E sufficient by conventional methods with vitamin E deficient subjects. The release of MDA from erythrocytes from vitamin E deficient subjects was clearly greater (44.1 +/- 18.8% vs 2.0 +/- 1.8%) than for control subjects (p less than 0.001). PMID- 4042379 TI - Basal level of human growth hormone (hGH) in normal serum. PMID- 4042378 TI - Direct automated assay method for serum or urine levels of ketone bodies. PMID- 4042380 TI - A simple method for quantitative determination of lipoprotein-X (LP-X) in human serum. PMID- 4042381 TI - Hypnogenic paroxysmal dystonia: epilepsy or sleep disorder? A case report. AB - A patient was studied who every night experienced several attacks characterized by loud screaming, violent movements of limbs and trunk, and a tonic phase. No epileptiform activity was noted preceding or following these attacks. Prolonged EEG and videotape recordings before and after sleep deprivation, along with neuropsychological and pharmacological data, support the hypothesis of a seizure disorder involving the left temporal region. Nocturnal attacks completely disappeared with carbamazepine. This therapeutic effect was still present after six months of treatment. Sleep organization was also greatly influenced by this medication. The most striking change was the marked and sustained increase of stages 3 and 4 NREM sleep after treatment. PMID- 4042382 TI - Pattern-reversal visual evoked potential in a case of nitrous oxide abuse and recovery. AB - Pattern reversal visual evoked potentials were recorded in a dentist who had abused nitrous oxide while he showed neurologic impairment and during recovery. The latency of the major positive peak (P100) remained constant during both phases. However, the amplitude of this peak was markedly reduced during the stage of neurologic involvement, and increased during recovery after withdrawal. The clinical significance of this is discussed. PMID- 4042383 TI - Somatosensory evoked potentials following stimulation of the tibial, peroneal and sural nerves using four different montages. AB - Cortical and lumbar somatosensory evoked potentials (SEPs) were recorded following unilateral stimulation of the tibial, peroneal and sural nerves in 20 normal adults. The active cortical electrode (Cz) was referred to either a cephalic (mid-forehead, contralateral central scalp, linked ears) or a non cephalic (contralateral shoulder) site. The configuration of the short-latency cortical SEP waveforms was nearly identical irrespective of the nerve stimulated or the location of the reference. Central conduction times (CCTs) were also calculated by subtracting the peak latency of the lumbar SEP from that of the primary cortical response following stimulation of the tibial and peroneal nerves. A stronger relationship was consistently observed between the absolute cortical latency and height than between CCT and height. The potential clinical applications of the results are discussed. PMID- 4042384 TI - An assessment of the variability of early scalp-components of the somatosensory evoked response in uncomplicated, unshunted carotid endarterectomy. AB - Although many publications deal with the usefulness of the SER in CEAs, the criteria of calling a SER abnormal during a CEA are largely arbitrary. One way to define the limits of normalcy for SERs during the CEA will be to analyze the SER tracings obtained during unshunted and uncomplicated (intra- and postoperative) CEAs. In 23 such CEAs (10 right, 13 left; clamptime 10-23 mins.), data analysis at the ipsilateral parietal electrode, on stimulation of the contralateral median nerve (square pulse -5.1/sec, 10-30 V, 200 microseconds; bandpass-30-3000 Hz trials-500 stimuli), revealed that (1) latency fluctuations of the N20 (21.4 msec) were narrowest, being less than 1.5 msec different during and after clamping compared to the preclamp latency in all 23 CEAs, whereas those of P25 (27.4 msec) and N35 (38.5 msec) were greater than 2.0 msec different from the preclamp latency in 3 and 8 CEAs respectively, and (2) the amplitudes of N20, P25 and N35 measured from the preceding peak of opposite polarity, fell to less than 75% of the preclamp value on 3, 4 and 7 CEAs respectively. It is concluded that N20 was the most stable of the first three short-latency components in the SER and should perhaps be most relied upon to predict abnormality of the SER during CEAs. PMID- 4042385 TI - Ambulatory EEG: a community hospital prospective study with analysis of patient outcome. PMID- 4042386 TI - Saline activation of pseudoepileptic seizures: clinical EEG and neuropsychiatric observations. AB - Twenty patients with suspected pseudoseizures underwent saline infusion during prolonged sleep deprived EEG with video monitoring and nasopharyngeal electrodes. No patients had definite clinical evidence of epilepsy, but 35% had abnormal EEGs, 10% with epileptiform activity. Patients with epileptiform discharges did not experience pseudoseizures with saline infusion. Patients with generalized EEG slowing responded to saline infusion with characteristic seizures. Three groups of patients were differentiated. Eight patients had characteristic attacks with saline infusion, and in these patients females predominated, mean age was lower, and somatoform disorder was common. Six patients each either failed to respond to saline or had episodes different from their characteristic spells. These patients were more often male and more often had diagnoses of personality disorders. The findings suggest that, although saline infusion may identify pseudoseizures and confirm their non-epileptic nature, some patients may not be sufficiently suggestible to respond to saline infusion, while others may have non-epileptic attacks which are different from the spells under evaluation. Psychiatric and neuropsychological features suggestive of pseudoseizures may be more readily identified by psychiatric interview or psychometric testing. Ethical issues regarding saline infusion in the guise of a potent convulsant should also be considered. PMID- 4042387 TI - Relationship between serum sodium and blood pressure in morbid obesity. AB - We evaluated the relationship between blood pressure and serum sodium level in morbidly obese patients. Forty patients had at least 2-3 blood pressure measurements and two measurements of serum sodium. The correlation between serum sodium and systolic blood pressure was 0.66 (p less than 0.01). The correlation between diastolic pressure and serum sodium was 0.40 (p less than 0.025). Our observation linking serum sodium to blood pressure provides a lead to study mechanisms common to regulation of blood sodium and blood pressure in morbid obesity. PMID- 4042388 TI - Lack of effects of maternal salt intake on blood pressure of offspring in Dahl salt-sensitive rats. AB - Inbred Dahl salt sensitive (S/JR) and salt resistant (R/JR) rats were used to look for effects of varying maternal intake of salt (NaCl) on the blood pressure of the offspring. Neither the blood pressure at weaning nor the blood pressure response to postweaning high salt diet of S/JR or R/JR rat pups was affected whether their mothers had eaten high salt (8% NaCl) or low salt (0.15% NaCl) diet during gestation. Similarly, maternal salt intake during lactation had no effect on the blood pressure of the offspring at weaning or the blood pressure response to salt feeding after weaning. Na+ was higher and K+ was lower in milk of S/JR compared to R/JR mothers during the last half of the lactation period, but dietary salt intake did not influence milk Na+ or K+. Previous cross-fostering experiments show that this strain difference in milk electrolytes does not influence S pups blood pressure. It is concluded that neither maternal salt intake nor the existing changes in milk Na+ have any influence on the blood pressure of Dahl salt sensitive rat pups in contrast to the marked effects of salt intake in these rats after weaning. PMID- 4042389 TI - Decreased core-to-skin heat transfer in mild essential hypertensives exercising in the heat. AB - In previous reports (1,2) we examined the physiological responses of normotensive and essentially hypertensive men to steady state leg exercise (at 40% V02max) in a warm (38 degrees C dry-bulb, 28 degrees C wet-bulb) environment. Those results are reviewed. Additionally, in this paper we report relative core-to-skin heat transfer (HT) characteristics of these two groups, matched for age, aerobic fitness, and body composition, but differing in resting blood pressure. Forearm skin blood flow (as measured from changes in total forearm blood flow) was relatively reduced in the hypertensives. This resulted in a similar (but slightly compensated) reduction in HT, e.g., at minute 30, the hypertensives had 81% less skin blood flow and 56% less HT than their normotensive counterparts. This finding has important implications for unmedicated mild hypertensives exercising or working in hot environments. PMID- 4042390 TI - Slow-release nifedipine as a single or additional agent in the treatment of essential hypertension--a placebo-controlled crossover study. AB - The efficacy and safety of a new slow-release formulation of nifedipine ("Adalat Retard") were assessed in a double-blind cross-over trial in 19 subjects with essential hypertension (14 male, 5 female--ages: 34-72 years), 14 of whom continued previous antihypertensive medication. There were two 6 week treatment phases in which nifedipine 20 mg twice daily and placebo tablets twice daily were administered in random order. Supine mean blood pressure was 115 +/- 2 mm Hg during the placebo phase and 105 +/- 2 mm Hg during the nifedipine phase (p less than 0.001); and standing mean blood pressure was 121 +/- 2 mm Hg after placebo and 110 +/- 2 mm Hg after nifedipine (p less than 0.001). The magnitude of the blood pressure difference between the two phases was not related either to age or to the placebo phase blood pressure. The hypotensive effect of nifedipine was observed when administered as a single agent or in combination with diuretic and/or beta blocker. Heart rate was increased after nifedipine--75 +/- 2 beats/minute compared with 71 +/- 2 beats/minute after placebo (p less than 0.01). In this dose nifedipine (as "Adalat Retard") is an effective hypotensive agent which is a useful addition to presently available therapy. PMID- 4042391 TI - Heterogeneity of Kallmann's syndrome. AB - Kallmann's syndrome is a rare condition defined as a combination of hypogonadotropic hypogonadism and anosmia. The present study shows two genealogical tables. In the first family six male members in four generations had Kallmann's syndrome. All carrier females seemed to have normal fertility and normal olfactory function. X-linked recessive or - less probable - dominant sex linked inheritance was considered to be most probable. Renal malformation was discovered in one and was excluded in two affected members. In the second family only one affected female was discovered. She had a monozygotic twin sister with normal pubertal development, but also total anosmia. Four individuals with anosmia alone were found in this family, but no further cases of hypogonadism. The possibility of an acquired hypothalamic insufficiency on the basis of hereditary anosmia is discussed. PMID- 4042392 TI - Partial trisomy 12q: clinical and cytogenetic observations. AB - High resolution chromosome banding showed a male infant with profound mental retardation, hypertonia and multiple congenital anomalies to have the karyotype 46,XY,-der (2),t(2;12)(q37.3;q24.13)pat. Most of the clinical findings were compatible with those of the previously described cases with partial trisomy 12q. Some of the clinical features seem to disappear with increasing age. PMID- 4042393 TI - Partial trisomy 5q and partial monosomy 5q within the same family. AB - The observation of partial trisomy for 5q31-5qter and partial monosomy for the same segment in two offspring within the same family is presented. Their normal mother was a balanced carrier of a reciprocal translocation 46,XX,t(5;10) (q31.3;q26). The trisomic female had craniofacial dysplasia, a short neck, clinodactyly of the 5th fingers, a small umbilical hernia, arhinencephalia, cerebellar hypoplasia, atrial septal defect, an accessory spleen, bifid uterus and vagina, hypoplastic ovaries. Potter syndrome with cystic dysplasia of the left kidney and agenesis of the right, urethral atresia, uterus unicornus with utero-urethral fistula, true hermaphroditism with two ovaries and one testicle were found in her stillborn sister. Analysis of the manifestations of monosomy 5q and trisomy 5q in the same family supports a well known fact that the effects of deletions are more pronounced than those of duplications for the same segments. PMID- 4042394 TI - EEC syndrome without ectrodactyly? Report of 8 cases. AB - Eight cases are presented from two families with a variable manifestation of the EEC syndrome. In the first family only one of three affected persons suffers from limb defects. In the second family all five affected have a different pattern of symptoms and only two of them show limb defects. The described families as well as at least one literature report confirm that ectrodactyly is not an obligate symptom of the EEC syndrome. PMID- 4042395 TI - Expression of X-linked hypohidrotic ectodermal dysplasia in six males and in their mothers. AB - Six male patients with confirmed X-linked hypohidrotic ectodermal dysplasia and their mothers were studied to determine the variation of expressivity in patients and heterozygotes, major problems of the patients, and to find a clue to pathogenesis. The number of teeth, conic in shape, in patients varied from none to 14. In addition to hypohidrosis and hypotrichosis, dry skin, reduced salivation, hoarseness and hypoplasia of the nipples were common signs. Five patients had frequent respiratory infections. The mothers lacked more than four permanent teeth, one mother had hypodontia in the deciduous dentition. The sweat pore counts were low in patients, and lower than normal in the mothers. All patients carried beta-hemolytic streptococci, four of them group A either in nose or pharynx, without symptoms. Immunoglobulin values, including IgA were normal in serum and saliva. Unexpectedly, serum parathyroid hormone concentrations both in patients and mothers were low. The major problem of the families was the risk of hyperpyrexia due to hypohidrosis, but the patients' concern was mostly because of their facial appearance. PMID- 4042396 TI - Heritable fragility at 11q13 and 12q13. AB - The chromosomes of two mentally retarded probands were investigated because they were suspected of having the fragile X syndrome. However two other fragilities were detected. In one patient a fra(11)(q13) was found and in the other a fra(12)(q13). Family studies revealed that both fragile sites were real heritable ones. Besides these two heritable fragile sites, the common fragile site at 3p14 was frequently observed. The effects of BUdR, FUdR and methotrexate on the frequency of the three fragilities were studied. The two heritable fragile sites differed from the common fragile site at 3p14 with respect to their inducibility by FUdR and methotrexate. PMID- 4042397 TI - Duchenne-like muscular dystrophy in two sisters with normal karyotypes: evidence for autosomal recessive inheritance. AB - Two sisters, products of a consanguineous marriage (with a total of 12 children) showed muscle weakness at ages 7 and 6 yrs, respectively. The symptoms progressed rapidly and the patients were confined to wheelchairs at ages of 12 and 11 yrs, respectively. They had mild facial weakness and pseudohypertrophy of the calves, but neither cardiomyopathy nor mental retardation. Serum CK activities exceeded upper normal limit by 70 to 85-fold. Muscle biopsies were compatible with muscular dystrophy. Both girls had a normal karyotype. The healthy mother had mild CK elevations in two out of three occasions, but the muscle biopsy was normal. Three out of the six unaffected sibs had mild CK elevations. The findings support the concept of severe progressive muscular dystrophy with autosomal recessive inheritance. The condition is clinically indistinguishable from Duchenne muscular dystrophy. PMID- 4042398 TI - Cornelia de Lange syndrome in a mother and daughter. AB - The Cornelia de Lange syndrome was first described in 1933. Since then, more than 250 cases have been described in the medical literature. It has generally been considered to be sporadic, but several authors have raised the possibility of genetic factors. We present a mother and child affected with Cornelia de Lange syndrome and raise the possibility of autosomal dominant inheritance. PMID- 4042399 TI - An unusual variant chromosome 9 with an extra C-negative, G-dark segment in the short arm. AB - An unusual variant chromosome 9 is described in a mother and a daughter: an extra G-dark, C-negative and G-11 negative chromosomal segment is present in the short arm in the absence of apparent phenotypic effects. This extra material is also Ag As negative and exhibits a fluorescence similar in intensity to that of band 9q21 when stained by QFQ and DAPI/AMD, and to that of band 9p13 in RBA-banded preparations; it is slightly less fluorescent when R-banded by chromomycin A3. The possibility of an association with an increased risk of spontaneous abortion is presented. PMID- 4042401 TI - About diploid-tetraploid mosaicism. PMID- 4042400 TI - A complex structural rearrangement of chromosome 4 in a woman without phenotypic features of Wolf-Hirschhorn syndrome. AB - A 32-year-old mentally retarded woman was found to have a complex rearrangement of one chromosome 4. Her karyotype is interpreted as 46,XX,inv(4) (pter--- p14::q12----p14::q12----qter) del (4) (pter----15.33::p15.2----qter). Clinically she does not show the features of the Wolf-Hirschhorn syndrome. Her phenotype and cytogenetic findings are compared with 2 other reported cases of 4p-without Wolf Hirschhorn syndrome. PMID- 4042403 TI - Imaging techniques in muscular dystrophies. PMID- 4042402 TI - 46,X,i(Xq) karyotype in a patient with hypoplastic left heart. PMID- 4042404 TI - Prenatal testing and twinning. PMID- 4042405 TI - Frequency of fragile X chromosome in normal females. AB - Because of the ambiguities in diagnosing carriers of the fragile X syndrome, we studied thirty-six normal females to determine whether the fragile site at Xq27 can be seen in noncarrier females and at what frequency. A fragile site at Xq27 was identified in one out of thirty-six females, occurring at a frequency of 0.5% in her peripheral lymphocytes. We conclude that the fragile Xq27 site occurs only rarely in noncarrier females and that each laboratory should determine its own baseline frequencies of fragile X in order to most accurately distinguish between normal and carrier women. PMID- 4042406 TI - The Dowling Oration 1984. Device and rule. PMID- 4042407 TI - The bergapten content of garden parsley and its significance in causing cutaneous photosensitization. PMID- 4042408 TI - Acanthosis nigricans in monozygotic twins with post receptor defects causing insulin resistance. PMID- 4042409 TI - Short contact crude coal tar therapy for psoriasis. PMID- 4042410 TI - Sarcoidosis of the vulva. PMID- 4042411 TI - Elastosis perforans serpiginosa and pseudoxanthoma elasticum-like skin change due to D-penicillamine. PMID- 4042412 TI - Pseudomilia--widespread cutaneous calculi. PMID- 4042413 TI - Kaposi's sarcoma and angioimmunoblastic lymphadenopathy. PMID- 4042414 TI - Urticaria from paracetamol. PMID- 4042415 TI - Simultaneous turnover of normal and dysfunctional C1 inhibitor as a probe of in vivo activation of C1 and contact activatable proteases. AB - Simultaneous turnover of normal and dysfunctional C1-inhibitor (C1-INH) was carried out in 10 normal subjects and 13 patients with rheumatoid arthritis as a measure of the in vivo activation of C1 and the contact activatable enzymes. In the first series of experiments, dysfunctional protein We was used in simultaneous turnover studies in five normal subjects and nine patients. The fractional catabolic rate of the dysfunctional C1-INH, We, (FCR(d)) was unchanged in both groups but the fractional catabolic rate of the normal C1-INH (FCR(n)) was faster in the patients compared to the controls, in particular patients with vasculitis. The enzyme-dependent catabolism defined as FCR(n-d) X concentration of C1-INH X plasma volume, was raised in the patient group, and correlated with disease activity score (r = 0.83, P less than 0.05). Neither FCR(n) nor FCR(d) was dependent on C1-INH concentration. The latter was higher in the patients (206 mg/l compared with 155 mg/l) indicating a very high synthetic rate in the patients (280.81 micrograms/kg/h compared with 179.77 micrograms/kg). In the second series of turnovers in six patients and five normal subjects, another dysfunctional C1-INH, at, was used. The FCR of C1-INH was slower than C1-INH (We) (1.88%/h compared with 2.7%/h). Enzyme-dependent catabolism of C1-INH in these patients were raised and also correlated with disease activity score (r = 0.82, P less than 0.05). PMID- 4042416 TI - Successful tumour immunotherapy: possible role of antibodies to anti-inflammatory factors produced by neoplasms. AB - Phenol-saline tumour extracts, active in the immunotherapy of bovine ocular squamous cell carcinoma (BOSCC), were used to immunize mice. The immunized mice became resistant to the depression of delayed type hypersensitivity (DTH) reactions by products of BOSCC cells or cultured mouse or rat tumour cells. They also showed partial resistance to the growth of an unrelated tumour. Monoclonal antibodies to a type C retrovirus protein, p15E, also induced resistance to the depression of DTH by products of BOSCC and mouse tumours. It is suggested that successful immunotherapy of BOSCC is associated with the induction of resistance to anti-inflammatory or immunosuppressive tumour cell products, allowing the operation of host defences, and that these products share antigenic determinants with a retrovirus protein. PMID- 4042417 TI - Effect of human colostrum and infant formula on the phagocytic activity of macrophages. I. Resident and stimulated mouse peritoneal macrophages. AB - Phagocytosis and degradation of radiolabelled human transferrin-anti-transferrin immune complexes by resident and stimulated mouse peritoneal macrophages was inhibited by liquid infant formula, particularly in the case of resident cells. Mouse peritoneal macrophages exposed to infant formula were shown by immunofluorescence to bind casein and beta-lactoglobulin, but there was little binding of alpha-lactalbumin. Comparison of various artificial milks, cow's milk and purified casein indicated that both the concentration and the degree of denaturation of casein may be important in the impairment of macrophage function by milk. It is suggested that bottle feeding of infants might result in impairment of macrophage function in the small intestine. PMID- 4042418 TI - MRL mice show an age-related impairment of IgG aggregate removal from the circulation. AB - The fate of heat-aggregated human IgG (HAGG) was examined in young and old autoimmune MRL-lpr/lpr and MRL-+/+ mice and compared to BALB/c mice of different ages. Following iv injection of [125I] HAGG the older MRL-lpr/lpr and MRL-+/+ mice showed impaired hepatic and splenic uptake of this material. In addition the clearance rate of HAGG was significantly slower in the older MRL-lpr/lpr mice (t1/2 = 50 min) when compared to younger controls (t1/2 = 13 min) although this age-related retardation of clearance was not observed in the MRL-+/+ mice. No difference was seen in the clearance rate or organ uptake studies of the two age groups of BALB/c mice. Catabolic studies using trichloracetic acid suggested that the HAGG was catabolized to smaller fragments with time but not to such a great extent in the older diseased animals, again no age-related difference was seen in the BALB/c mice. Our studies suggest that with age both autoimmune strains of MRL mice show some saturation of the mononuclear phagocytic system (MPS) and that this process is more obvious in the MRL-lpr/lpr mice. MPS saturation may play a role in the pathogenesis of autoimmune disease in these mice. PMID- 4042419 TI - Immune function and survival in pleural mesothelioma. PMID- 4042420 TI - Report of the British Society for Immunology Working Party on Clinical Immunology: 1984. Guidelines for training the physician immunologist. PMID- 4042421 TI - Interference of hepatitis B virus surface antigen with natural killer cell function. AB - The influence of purified hepatitis B virus surface antigen (HBsAg) preparations or of supernatants derived from PLC/PRF/5 cell line (which produces HBsAg) on human natural killer (NK) activity was examined. Lymphocytes pre-incubated with HBsAg and subsequently washed showed a significant decrease in NK cytotoxicity against K-562 target cells. This effect was reversible and dose-dependent. In addition, pre-incubation with either HBsAg or PLC/PRF/5 supernatants inhibited in a reversible manner lymphocyte--K-562 conjugates and the binding of B73.1 monoclonal antibody (MoAb), which recognizes Fc receptors on NK cells. This effect was not observed with HNK-1, T3, T4, T6, T8 and T11 MoAb. HBsAg was non toxic to lymphocytes, and ineffective with K-562 target cells. Beta-interferon did not modify HBsAg-mediated inhibition, when added either before or during the contact with HBsAg. Moreover, no modification was observed when neutrophils (at various neutrophil:lymphocyte ratios) were added, even though HBsAg is known to stimulate neutrophils to produce oxygen radicals which may modulate NK activity. We speculate that HBsAg produces these effects by reacting into receptor sites (possibly Fc receptor sites) on NK cell membrane. The overall significance of our results in relation to hepatitis and hepatocellular carcinoma is discussed. PMID- 4042422 TI - Surface markers and cytotoxic activity of blood natural killer cells studied at the single cell level in Hodgkin's disease. AB - Purified peripheral blood lymphocytes (PBL) from nine untreated patients with Hodgkin's disease (HD), two HD patients in complete remission and 17 healthy donors were studied for natural killer (NK) cell activity against the K-562 cell line using a single cell cytotoxic assay, which allowed enumeration of effector cells and characterization of their surface membrane phenotypes after staining with monoclonal antibodies. The frequency of NK cells was significantly lower in HD patients than in controls (mean % +/- s.d., 1.9 +/- 0.9 and 2.8 +/- 1.2, respectively), while the fraction of target binding cells was similar in the two groups. The fraction of cytotoxic lymphocytes increased after pre-treatment of PBL with 500 iu leucocyte interferon in all tested control donors (n = 12) and the two patients in remission but only in four of seven untreated patients. No relation between the impaired NK cell frequency and age, tumour histology and clinical stage could be revealed. Subtyping of the target cell binding NK cells by monoclonal antibodies disclosed a marked heterogeneity of effector cells. NK effector cells reactive with M1 and anti-Ia antibodies were enriched while T3+ and T4+ NK lymphocytes tended to be reduced as compared to PBL. There was no difference between patients and healthy donors with regard to the surface antigen patterns of NK cells. Interferon treatment did not alter significantly the phenotypic characteristics of cytotoxic lymphocytes in patients and controls. It is concluded that the impairment of NK cell activity in HD is partly attributed to a lower frequency of cytotoxic effector cells among a normal number of target binding cells. The defect could not be attributed to a selective defect of effector cell subsets. PMID- 4042423 TI - Susceptibility and amplification of sensitivity in contact dermatitis. AB - We have examined the hypothesis that people who develop contact allergies to environmental substances do so because they have heightened susceptibility. Analysis of data from 2200 consecutive patients tested with the 20 commonest antigens in a patch-test clinic showed that more people developed multiple contact allergies than would be predicted from the frequency of single allergies; the excess was too great to be explained by chance and increased with number and rarity of the combinations of sensitizers. The possibility that this was due to enhanced individual susceptibility to sensitization rather than concomitant exposure to several sensitizers was confirmed by showing that patients with multiple allergies are more readily sensitized experimentally, and to a greater degree than normal, by dinitrochlorobenzene (DNCB), an unrelated antigen. The defect involves induction rather than expression of sensitivity. Amplification of the response to DNCB is proportional to susceptibility (calculated from the ratio of observed prevalence of multiple allergies to that predicted from the prevalence of single allergies) throughout the range from normal subjects, through those with a single sensitivity, to those with rare, multiple allergies. Therefore, we conclude that individual susceptibility is an important factor in the development of contact dermatitis, and occurs by a non-antigen-specific amplification of immune sensitization. PMID- 4042424 TI - Thyroid function in mice with experimental autoimmune thyroiditis. AB - Mice of strains high and low responders to thyroglobulin were immunized with mouse thyroglobulin emulsified in Freund's complete adjuvant. Groups of mice were killed at weekly intervals and the serum thyroxine concentration was measured with a solid-phase RIA while the titre of thyroglobulin antibodies was determined by passive haemagglutination and the magnitude of thyroid infiltration with mononuclear cells was scored. In other groups of mice, similarly immunized, radioactive iodine uptake was measured at various times after immunization. In almost all mice the lowest level of thyroxine and the lowest radioiodine uptake were observed 2 weeks after immunization. There was no clear relationship between the thyroid function and the titre of thyroglobulin antibodies or the extent of the cellular infiltrates in the thyroid. PMID- 4042425 TI - Serum from patients with pernicious anaemia blocks gastrin stimulation of acid secretion by parietal cells. AB - We examined 51 sera from patients with pernicious anaemia for their capacity to block maximal gastrin stimulation of acid secretion by isolated rodent gastric parietal cells. 14C-aminopyrine accumulation was used as the index of acid secretion in vitro. Sera from patients with pernicious anaemia gave significantly (P less than 0.005) more block of maximal gastrin stimulation of acid secretion (61.7 +/- 37.8%) than sera from 10 patients with systemic lupus erythematosus (19.6 +/- 17.7%), 10 with scleroderma (34.2 +/- 22.3%), five with rheumatoid arthritis (22.4 +/- 15.6%) or 30 from healthy persons (27.4 +/- 12.8%). Maximal histamine stimulation of acid secretion was not inhibited. The blocking factor was present in serum IgG fractions, and serum and IgG fractions gave parallel dose-response and dilution curves. The serum block was abolished by absorption with gastric mucosal cells and correlated with the presence of parietal cell surface autoantibody. We conclude that serum immunoglobulin in pernicious anaemia can block gastrin stimulation of acid secretion and suggest that this block may be mediated by competition with gastrin for surface receptors on parietal cells. PMID- 4042426 TI - Inappropriate responses to Mycobacterium leprae infections--C reactive protein in man and serum amyloid P in mice. AB - In a study of C-reactive protein (CRP) levels in the sera of 77 patients with leprosy, it was found that in the majority of newly diagnosed patients, the level was within the normal range for a healthy Malaysian population. Elevated levels did occur, but were usually found in patients with complications, and were more likely to occur in patients who had been receiving drug treatment for some time. This suggested that Mycobacterium leprae infection by itself does not stimulate CRP synthesis and could reflect a failure of synthesis by macrophages of interleukin-1, or related molecules. This was supported by the study of an analogous acute phase protein, serum amyloid P (SAP) in mice bearing M. leprae from human sources in their hind footpads. Such mice showed no significant difference in SAP levels from control mice. PMID- 4042427 TI - Suppression of collagen type II-induced arthritis by transfer of lymphoid cells from rats immunized with collagen. AB - Rats were immunized with type II collagen to induce polyarthritis. Spleen and lymph node cells were taken at various times and transferred to normal syngeneic animals. Disease was not observed in recipients of cells taken from donors either during the pre-clinical phase or the acute clinical phase of the disease. However, arthritis could not be induced in the recipient animals that had received cells taken from donors during the preclinical phase. Animals receiving cells from donors with clinical disease appeared to have a normal susceptibility to disease induced subsequently. In contrast with the differences in their susceptibility to induced disease, all recipient animals made unmodified antibody responses to a challenging injection of type II collagen. The results showed that before the appearance of clinical disease in CII immunized rats, there were cells in the spleen and lymph nodes that inhibit the development of disease but not antibody responses. PMID- 4042428 TI - Platelet involvement in the nephritis of acute serum sickness in rabbits: protection by dipyridamole and FUT-175. AB - In the acute serum sickness model in rabbits, we investigated platelet release of 5-HT, platelet surface immunoglobulins, and platelet aggregation in response to ADP, together with the effect of dipyridamole and the Clr antagonist FUT-175. The immune release of 5-HT from platelets occurred between 4 and 6 days after injection of bovine serum albumin (BSA), before immune elimination and proteinuria, but coincident with the appearance of immune complexed BSA in the circulation. Nevertheless, platelet turnovers were not detectably accelerated. Treatment with dipyridamole 50 mg/kg/24 h prevented the release of 5-HT and inhibited proteinuria, glomerular hypercellularity and immune complexes in the glomeruli. Using the Clr antagonist FUT-175, similar abrogation of the disease was obtained. We conclude that in the nephritis of acute serum sickness in rabbits, some of the immune release from platelets may be the result of immune complex binding to the platelet, perhaps through the receptor for C3b. PMID- 4042430 TI - IgG (Gm) allotypes and multiple sclerosis in a French population: phenotype distribution and quantitative abnormalities in CSF with respect to sex, disease severity, and presence of intrathecal antibodies. AB - The association of a given Gm allotype or phenotype with MS susceptibility, as previously described in some Caucasian populations, was not observed in a large French MS group, whether or not considering the possible influence of sex or disease severity. This result could be related to variations in geographical distribution of Gm alleles and MS susceptibility gene(s) or suggests the simultaneous involvement of Gm and other genetic system(s). In contrast, the corresponding CSFs exhibited already known MS-associated abnormalities of IgG1 (G1m) allotype contents, which therefore did not merely result from a Gm associated MS susceptibility. These quantitative abnormalities were not sex dependent, but may fluctuate with MS severity. The G1m allotype levels in each CSF were not correlated with titers of various intrathecal antibodies but with the number of antibody specificities detected, a picture arguing for a polyclonal, non-antigen-specific activation of G1m allotype-producing B cells present in MS brain. PMID- 4042429 TI - Antigenic analysis of immune complexes formed in normal human pregnancy. AB - Immune complexes, isolated from pregnancy sera by absorption to immobilized protein A, were dissociated and the antigen components separated from the IgG antibodies, which possessed immune reactivity directed against the plasma membrane of the syncytiotrophoblast layer of the placenta. Gel filtration studies demonstrated that five separate antigens could be identified and were of placental origin, as observed by their reactivity in an ELISA with affinity purified anti-trophoblast antibodies isolated from maternal sera. The five antigens of apparent mol. wt 2 X 10(6), 400,000, 150,000, 13,000 and less than 10,000 daltons were designated maternally recognised trophoblast antigens (MRTA), numbers V-IX; the relative proportions of these antigens in the sera were 14%, 68%, 16%, 0.5% and 1%, respectively. Immune complexes were also identified in nulliparous non-pregnant female sera and consisted of the 150,000 and the less than 10,000 daltons antigen components. The relationship between the MRTA present in the immune complexes and the MRTA (numbers I-IV) previously identified as components of the trophoblast plasma membrane is discussed. PMID- 4042431 TI - Interaction of mutant lpr gene with background strain influences renal disease. AB - The mutant gene lpr on the MRL/Mp strain of mice is responsible for converting a late onset glomerulonephritis into an early, aggressive, and fatal renal disease. This gene induces the proliferation of a unique subset of lymphocytes, the production of a variety of autoantibodies and shortened survival in MRL/Mp as well as in the genetically distinct strains C3H/HeJ, C57BL/6J, and AKR/J. The present study examined in detail the role of the lpr gene in the formation of lupus nephritis. The results show that C3H-lpr and B6-lpr mice do not develop nephritis while the AKR-lpr strain has a mild form of renal disease. None of these newly constructed congenic mutant strains have the severity of proteinuria or the degree of renal pathology characteristic of MRL-lpr mice. Thus, the lpr gene alone is insufficient in producing severe renal injury. The interaction of the lpr gene with other factors is required for the induction of life-threatening lupus nephritis. PMID- 4042432 TI - Inhibition of neutrophil-mediated cytotoxicity by exogenous adenosine 5' triphosphate. AB - Human polymorphonuclear leukocytes (PMNs) obtained from normal donors kill human tumor cells in vitro. However, if adenosine 5'-triphosphate (ATP) is added to the neutrophil tumor cell suspensions in micromolar concentrations (10-100 microM), there is marked inhibition of neutrophil-mediated cytotoxicity. The inhibitory activity resulted from an effect of ATP on both the effector cells as well as the target cells. When either the effector cells or target cells were preincubated with ATP they became resistant to the effects of the cytotoxic neutrophils. In addition, inhibitory activity was specific to ATP; as it was not demonstrated with GTP, UTP, or CTP. However, when the other adenosine compounds (AMP and ADP) were tested, both AMP and ADP had some inhibitory activity. Cytotoxicity was also inhibited when 100 microM of ATP were added to the neutrophil monolayers either at the time of addition of the tumor cells or 15-60 min after addition of the tumor cells whereas no inhibition of cytotoxicity occurred when ATP was added more than 1 hr after the initiation of the cytotoxic reaction. PMID- 4042433 TI - In vitro stimulation of lymphocytes from patients with rheumatoid arthritis. AB - Peripheral blood lymphocytes from patients with rheumatoid arthritis (RA) and from normal controls were compared in 20 microliters droplet cultures following stimulation with phytohemagglutinin or concanavalin A. The dynamics of proliferation were significantly changed in RA. Higher numbers of cells in culture were needed to achieve the same response. This may explain the low proliferative responses of lymphocytes from some patients with RA, and apparent changes of in vitro suppressor effects, reported by other authors. Diurnal variations of lymphocytes in RA patients were also studied. No differences in the response to mitogen of lymphocytes taken at 7 AM and 7 PM were found. PMID- 4042434 TI - Phenotypical and functional analysis of natural killer cells in sarcoidosis. AB - The frequency of cells reactive with natural killer (NK)-related monoclonal antibodies (MoAbs) HNK-1, NKP-15, B73.1, VEP-13, Ab8.28 has been evaluated in the peripheral blood and bronchoalveolar lavage (BAL) fluid of 39 patients with pulmonary sarcoidosis (including 19 cases with active sarcoidosis and 20 cases with inactive disease). This phenotypic analysis was carried out together with the NK in vitro functional evaluation of cell populations from peripheral blood and BAL fluid. In addition, inhibition studies were performed in order to evaluate the ability of alveolar macrophages (M phi) to modulate NK activity. Data from peripheral blood showed an increased number of mononuclear cells bearing HNK-1, NKP-15, Ab8.28, VEP-13, and B73.1 determinants in patients with active sarcoidosis with respect to patients with inactive disease and controls. The majority of HNK-1-positive cells lacked both Leu2 and Leu3 antigens when investigated in a double marker system. A parallel increase in the in vitro cytotoxicity assay has been demonstrated. On the other hand, only a few mononuclear cells recovered from BAL fluid displayed a surface pattern of NK cells. This small population of HNK-1-positive cells expresses the HNK-1/Leu3 phenotype and does not exhibit NK activity. The alveolar M phi from sarcoid patients, as well as alveolar M phi from controls, have the property of inhibiting the NK activity of autologous peripheral blood lymphocytes. The lack of lung NK function in patients with active sarcoidosis may be related to the presence of immature forms of NK cells and/or to the release of soluble factors by alveolar macrophages. PMID- 4042435 TI - Inhibition of platelet-activating factor by rabbit C-reactive protein. AB - Incubation of 0.5 nM platelet-activating factor (PAF) with 123 micrograms/ml C reactive protein (CRP) for 60 min at room temperature in the presence of 2 mM calcium resulted in total inhibition of the platelet-aggregating capacity of 0.5 nM PAF. There was no inhibition of platelet aggregation if PAF and CRP were added to the platelets simultaneously, without prior incubation of the mixture, or if calcium was not present during the incubation of CRP and PAF. The inhibitory effect of CRP (123 micrograms/ml) was dependent upon the time of incubation with PAF (1 nM). We observed 0, 42, and 85% inhibition of platelet aggregation with incubations of 0, 20, and 120 min, respectively. The inhibitory effect of CRP was also concentration dependent. After incubations of 20 min at room temperature with 0.5 nM PAF there was no inhibition of PAF-induced platelet aggregation using 12.3 micrograms/ml CRP with the inhibition increasing to 73% using 123 micrograms/ml CRP. Pretreatment of the platelets with CRP (123 micrograms/ml) for 60 min before addition of PAF did not affect the induction of platelet aggregation by PAF. These observations indicate that CRP inhibits PAF and strongly suggest that binding of CRP to PAF, presumably to the phosphocholine moiety of PAF, is required for this inhibition. PMID- 4042436 TI - Nephrotic syndrome due to scleroderma. PMID- 4042437 TI - Folic acid supplements in patients on chronic ambulatory peritoneal dialysis. PMID- 4042438 TI - Sicca syndrome in mesangial IgA glomerulonephritis. AB - Schirmer-test, history of conjunctivitis, salivary gland scintigraphy and SSA/SSB (Ro/La) antibodies were evaluated in 24 patients with mesangial IgA glomerulonephritis (IgA-GN), 58 patients with non-IgA-GN and 100 healthy controls. A sicca syndrome (positive Schirmer-test) was found in 46% of patients with IgA-GN and 17% of non-IgA-GN and 8% of controls (p less than 0.001). Only one of the IgA-GN patients volunteered a history of xerosis of the conjunctiva, but upon questioning 17% reported a history of ophthalmological treatment for recurrent conjunctivitis. The observation adds another extrarenal facet to the syndrome of mesangial IgA-GN. Diminished tear production may be another (immune?) abnormality of the oropharyngeal system. PMID- 4042439 TI - Significance of endostreptosin antibody titers in poststreptococcal glomerulonephritis. AB - Endostreptosin (ESS) is an immunologically well defined cytoplasmic antigen of group A and some group C streptococci. ESS is probably the pathogenetic antigen of poststreptococcal glomerulonephritis (ASGN). Antibodies to ESS (ESS-Ab) were determined by microcomplement fixation in 1,102 patients and by ELISA in 105 patients. In 168 patients with ASGN (90 from the U.S.A. and 78 from Kuwait) the arithmetic mean titer was 45.2 (log10 1.40 +/- 0.606) and 50.2 (log10 1.51 +/- 0.394) respectively, both significantly elevated compared to 347 age matched children and adults from the U.S.A. whose arithmetic mean titer was 9.1 (log10 0.83 +/- 0.635) and 7.5 (log10 0.55 +/- 0.492) respectively and 139 children from Kuwait whose arithmetic mean titer was 15.7 (log10 0.92 +/- 0.495). In 51 patients with ASGN, the mean ELISA value was 67.5% higher than the values obtained from 54 normal age matched controls. Patients with streptococcal infections without renal involvement had only transiently and mildly elevated values. ESS-Abs in patients with other types of glomerulonephritides were in the range of normal. ESS-Ab titers do not parallel the titers of streptococcal exoenzymes. ESS-Ab titers are of importance for the differential diagnosis of renal diseases and of similar significance for the understanding of the pathogenetic mechanism of ASGN. They are possibly of significance for therapy in the form of an active vaccine. PMID- 4042440 TI - On four cases of hemolytic-uremic syndrome without microangiopathy. AB - Four cases of hemolytic-uremic syndrome (HUS) are presented in which light and electron microscopic examination of renal biopsies (2 cases) and light microscopic examination of the kidneys on autopsy material (2 cases) revealed no changes reflecting microangiopathy. Based on these findings and on personal observation of 197 cases of HUS with glomerular or vascular changes, it is considered questionable whether the results of animal experiments by Brain et al. [1962] and Brian and Brain [1968] can be transferred to man. The cause of hemolytic anemia in HUS is considered unclarified, except for cases in which hemolysis is triggered by neuraminidase-producing bacteria and viruses. PMID- 4042441 TI - Anaphylaxis: an unusual complication of hemodialysis. AB - Anaphylaxis is a rare complication of hemodialysis. Unless there is a high index of suspicion, symptoms may not be immediately recognized as a manifestation of hypersensitivity and prompt attention may be delayed. To improve physician awareness of this problem we report a patient who developed a severe anaphylactic reaction within minutes of beginning dialysis. Review of the literature indicates that hypersensitivity reactions are most commonly associated with Cuprophan dialyzers. Although the etiology has not been established, recurrence can be prevented by selection of a different type of dialysis membrane. PMID- 4042442 TI - Platelet aggregating factor in the epidemic form of hemolytic-uremic syndrome in childhood. AB - Plasma from six out of eleven children with the epidemic forms of hemolytic uremic syndrome caused the aggregation of homologous platelets as has been described in thrombotic thrombocytopenic purpura. IgG purified from normal adults inhibited the platelet aggregation induced by plasma collected from three children during the acute phase of the disease. This inhibition by IgG may contribute to the reported successful management by infusions of plasma or plasma exchanges. PMID- 4042443 TI - Rapid differentiation between glomerular and tubular proteinurias by high performance liquid chromatography. AB - This study regards the urinary protein of patients with renal diseases. Analysis was done by high-performance ion-exchange chromatography (HPIEC). In patients with steroid responsive nephrotic syndrome, the urinary proteins could be separated into about 10 peaks by HPIEC, whereas in the tubular dysfunction about 15 peaks were obtained. Main peaks obtained by HPIEC were identified by SDS polyacrylamide gel electrophoresis (SDS-PAGE) and immunochemical methods. HPIEC is an easy, reliable and rapid method for the estimation of glomerular and tubular proteinurias patterns, and it seems to be a good indicator of the selectivity of glomerular proteinuria. So, we recommend HPIEC for routine use in the clinical investigation of proteinuria. PMID- 4042444 TI - Effects of high CaCO3 supplements on serum calcium and phosphorus in patients on regular hemodialysis treatment. AB - The effect of high doses of CaCO3 on serum phosphorus and calcium (sPi,sCa) and the changes in serum aluminum (sAl) induced by Al(OH)3 interruption were investigated in patients on regular hemodialysis treatment. Some patients were administered Al(OH)3 and CaCO3, others only the former or the latter and others nothing. Al(OH)3 was stopped in all but one in whom it was only reduced, and CaCO3 was started or increased in all patients. A better control of sPi and serum Ca-Pi product was observed during high Ca supplementation, despite Al(OH)3 discontinuation, and was associated with a significant decrease of sAl. As expected, taking into account the dialysate Ca level of 4 mEq/l, a significant hypercalcemia occurred in some patients, especially in those who had a normal predialytic sPi without Al(OH)3 supplementation. Therefore, lowering the dialysate Ca concentration according to individual need and increasing interdialytic oral Ca supplements can be recommended with the dual purpose of keeping a positive Ca balance and correcting hyperphosphatemia. PMID- 4042445 TI - Disseminated histoplasmosis in dialysis patients. AB - The unusual occurrence of disseminated histoplasmosis in two dialysis patients residing in a nonendemic area is described; one on chronic hemodialysis, the other on continuous ambulatory peritoneal dialysis (CAPD). They both presented with nonspecific febrile illness with splenomegaly and/or pancytopenia. Rapid diagnosis was made with bone marrow biopsies and cultures. In the second patient, peritonitis secondary to histoplasmosis was documented by culture of the dialysate and at autopsy. This is the first such description in a CAPD patient. PMID- 4042446 TI - Uremic pericarditis in hemophilia A. PMID- 4042447 TI - Digoxin intoxication induced by verapamil in an uremic patient. PMID- 4042448 TI - Membranous glomerulonephritis in rheumatoid arthritis unrelated to gold or penicillamine treatment. PMID- 4042449 TI - Coagulation disorders. PMID- 4042450 TI - Adenosine triphosphate and adenosine: perspectives in the acute management of paroxysmal supraventricular tachycardia. AB - Adenosine triphosphate (ATP) and adenosine exert strong and transient depressant effects on the sinoatrial and atrioventricular (AV) nodes of the human heart. The AV nodal effects of these drugs explain their high efficacy in either terminating AV re-entrant supraventricular tachycardia or in slowing ventricular rate during atrial tachyarrhythmias. Their very short half-life enables repeated administration of increased doses without reaching toxic effects and explains the transient character of their frequent but benign side effects. These agents represent a good alternative to verapamil in the acute management of paroxysmal supraventricular tachycardia both in infants and adults. PMID- 4042451 TI - Management of the prolonged QT syndrome and recurrent ventricular fibrillation with an implantable automatic cardioverter-defibrillator. AB - Two patients with the prolonged QT syndrome and recurrent ventricular tachyarrhythmias are presented, one of them refractory to combination antiarrhythmic drug therapy and bilateral stellate ganglion blockade. We implanted and tested in vivo an automatic cardioverter-defibrillator to provide a cardiac monitoring system with the capability of delivering a 25 J electrical discharge to the heart if rapid ventricular tachycardia or ventricular fibrillation is detected. Arrhythmia induction in the electrophysiology laboratory confirmed the appropriate recognition of the arrhythmias in each patient, with prompt discharge of the device and resultant termination of the tachycardias. We suggest that implantation of such a device may provide an effective adjunct to antiarrhythmic drug therapy in the management of infrequent, but potentially lethal, ventricular arrhythmias occurring in patients with the prolonged QT syndrome. PMID- 4042452 TI - A case of Wolff-Parkinson-White syndrome: conduction through the Kent bundle seems to depend on the serum potassium level. AB - A 72-year-old man with Wolff-Parkinson-White syndrome and sick sinus syndrome had colon cancer, suggesting that the conduction of the Kent bundle depends on the serum potassium level. Because of severe diarrhea or furosemide administration, the serum potassium level in this patient was sometimes low. When it was less than 3.0 mEq/l delta wave or re-entrant tachycardia via the Kent bundle occurred. These were suppressed by the administration of potassium. On the other hand, when the serum potassium level was normal or high, neither effect was noted, and electrophysiological studies, done when the level was 3.2 mEq/l, showed no evidence of conduction by the accessory pathway. This suggests that conduction through the Kent bundle depends on the serum potassium level. PMID- 4042453 TI - Purity and transplantation properties of tumor cell suspensions. AB - Cell debris is inevitably produced by the mechanical and enzymatic procedures used to dissociate solid tumors. We investigated the influence of such debris on the i.v. and s.c. transplantability of B16 melanoma cells. Cell suspensions were centrifuged on a Percoll cushion to remove the debris, and the purified preparations were compared to untreated control suspensions. The i.v. injection of a massive dose (10(6) cells) of unpurified cells killed the animals within a few minutes, while the same amount of purified cells left the animals unaffected. When 5 X 10(5) cells were given, animals receiving purified cell suspensions had more extrapulmonary tumors at their time of death than those given unpurified cells. However, with a lower cell dose, 2 X 10(4) cells, there were no such differences in tumor incidence or distribution. PMID- 4042454 TI - Increase in radiosensitivity of lung micrometastases by hyperbaric oxygen. AB - Four-day-old artificial pulmonary micrometastases of two murine fibrosarcomas, designated FSA and NFSA, showed increased sensitivity to ionizing radiation by a factor of 1.13 when animals were exposed to hyperbaric oxygen breathing before and during irradiation, implying the presence of hypoxia in the micrometastases. At the time of irradiation the diameter of FSA and NFSA metastases was smaller than 200 and 100 microns, respectively, which, on the basis of oxygen diffusion, could not be responsible for hypoxia. It is assumed that hypoxia of micrometastases is passive, reflecting the radiobiological hypoxia of lung tissue that could exist under normal breathing conditions. PMID- 4042455 TI - Interaction of high or low metastatic related tumor lines with normal or lymphokine-activated syngeneic peritoneal macrophages: in vitro analysis of tumor cell binding and cytostasis. AB - Peritoneal macrophages from normal DBA/2 mice were found to bind significantly more cells of a syngeneic low metastatic lymphoma line (Eb) than cells of a high metastatic variant (ESb) derived therefrom. These differences were observed in three different assays, at 4 degrees C and at 37 degrees C, and at various ratios of macrophages to tumor cells. Upon co-culture with normal macrophages, a tumor cytostatic effect was consistently observed with Eb but not with ESb tumor cells. Further experiments indicated that macrophages exerted their growth inhibitory effect via direct tumor cell contact. Pre-treatment of tumor cells with neuraminidase or pre-treatment of macrophages with lens culinaris lectin increased the numbers of macrophages binding Eb and ESb tumor cells. Addition of D-galactose or D-mannose at 50 mM concentration led to an increase of tumor cell binding and tumor cytostatic activity. Taken together, these results suggest (i) that carbohydrates play a role in tumor cell recognition by macrophages and (ii) that the differences observed between Eb and ESb tumor cells may be due to differences in the expression of carbohydrates. Pre-activation of the macrophages by lymphokine(s) led to a short increase in their tumor cell binding capacity. Lymphokine activation resulted in a strong but also short-lived increase of tumor cytostatic potential. This was effective against both the low and the high metastatic tumor line. PMID- 4042456 TI - Attachment, spreading and growth in vitro of highly malignant and low malignant murine fibrosarcoma cells. AB - Highly malignant cell lines and low-malignant cell lines isolated from three different methylcholanthrene-induced murine fibrosarcomas were examined for their ability to attach to plastic dishes and collagen-coated dishes under serum-free conditions and in the presence of serum. Most of the cells from the three highly malignant lines attached and spread under all conditions. By 72 h, there was a significant increase in the number of cells indicating that at least some of the cells had undergone division (even in the absence of serum). In contrast, fewer of the cells from the three low-malignant lines attached and spread on the plastic or collagen substrates in the absence of serum or in the presence of 0.1 per cent serum. However, when 15 micrograms laminin per dish was added along with the low-malignant cells, they then attached and spread on the plastic and collagen-coated dishes. Previous studies have indicated that the highly malignant lines express cell surface antigens that cross-react with laminin while the low malignant cell lines do not. We speculate that the differences between the high- and low-malignant cells in the expression of cell surface laminin-like antigens contribute to the dissimilarities in attachment and spreading capacity. These differences may also contribute to the dissimilarity between these cells in malignant potential. PMID- 4042458 TI - Localization of plasminogen activator(s) in primary and secondary rat adenocarcinoma cells. PMID- 4042457 TI - Investigation of a new murine model of regional lymph node metastasis: characteristics of the model and applications. AB - The RC tumor, originally a renal adenocarcinoma very sensitive to different classes of chemotherapeutic agents, maintained in CDF 1 mice, was examined for its ability to metastasize. When inoculated into the foot (with 10(7) tumor cells), bulky metastases developed in the popliteal and para-aortic lymph nodes, in a constant and reproducible pattern, producing a massive microscopic invasion of the liver, the lungs and the spleen. The antigenicity tests demonstrated a low immunogenicity of the tumor. Chemotherapy assays showed that adriamycin and vincristine were effective against metastatic dissemination when administered early after tumor cell inoculation and principally when combined with excision of the tumor-bearing leg. The RC model appears to be suitable for the study of lymph node metastasis and could be used in chemotherapy trials of new drugs potentially effective against metastases of the lymphatic system. PMID- 4042459 TI - The course of metastatic disease originating from carcinoma of the prostate. AB - The purpose of this work was to study the time sequence and the patterns of the multistep spread of metastases. Fifty-one patients with stage D carcinoma of the prostate, previously treated for their primary tumor by surgery or radiotherapy combined with hormonal manipulation and for metastases by hormones and chemotherapy, were included in the study. The metastatic dissemination, characterized primarily by the appearance of bone metastases, could follow two distinct patterns: The first, characterized by sequential appearance of osteoblastic metastases, followed by the development of osteolytic bone lesions, and the second pattern, characterized by the simultaneous appearance of osteoblastic and osteolytic bone lesions. In cases with solely osteoblastic bone metastases, the lesions are hormone sensitive and long-lasting remissions could be obtained. The development of osteolytic bone lesions is usually accompanied by the recurrence of the primary tumor and appearance of metastases in other sites, such as the lymph nodes and lungs. Bone metastases became resistant to hormonal manipulation and with chemotherapy short remissions were obtained. The course of the terminal period is faster, with shorter survival times. The determination of serum acid and alkaline phosphatase levels seems to reflect the course of the disease during the initial period of the disease only, i.e. when bone metastases are sensitive to hormonal treatment. PMID- 4042460 TI - Influence of adoptively transferred thioglycollate-elicited peritoneal macrophages on metastasis formation in mice with depressed or stimulated NK activity. AB - The effect of thioglycollate-elicited macrophages (TG-M phi) on natural killer (NK)-cell activity and metastases formation in mice was investigated. Intravenously (i.v.) inoculated TG-M phi inhibited spleen NK activity of normal mice and abrogated polyinosinic: polycytidylic (poly I:C) induced augmentation of NK cell function. TG-M phi also inhibited the clearance of i.v.-injected radiolabeled B16 melanoma cells from the lungs of normal or poly I:C stimulated mice. Formation of experimental B16 melanoma metastases was dramatically increased in mice pretreated with TG-M phi. Administration of TG-M phi increased metastasis formation to a greater extent than anti-asialo GM1 serum, while anti asGM1 serum was more efficient than TG-M phi in depressing spleen NK cell activity. When mice with low NK reactivity (beige mice or mice treated with anti asialo GM1 serum) were inoculated with TG-M phi, there was a substantial additive augmenting effect on metastasis formation in the lungs. Treatment with poly I:C elevated NK-cell activity and had profound antimetastatic effects in normal but not in TG-M phi pretreated mice. The metastasis augmenting effect of TG-M phi was fully expressed in poly I:C-treated mice as well as in athymic nude mice. Inoculation of proteose peptone-elicited macrophages (PM phi), unlike TG-M phi, did not depress NK activity or augment metastasis formation in normal or poly I:C treated mice. However, since the inhibition of NK activity in TG-M phi-treated mice was relatively weak, and a substantial additional increase in metastases was observed in NK-depressed mice after transfusion of TG-M phi, it seems unlikely that the TG-M phi-induced inhibition of NK reactivity is entirely responsible for the augmented formation of metastases. Further studies revealed that i.v. inoculation of TG-M phi, but not PM phi, induced intravascular inflammatory reactions, and damage to endothelial cells and basement membrane of the lung vasculature. These reactions may contribute to increased tumor cell extravasation and metastasis formation in mice pretreated with TG-M phi. PMID- 4042461 TI - Lymph node metastasis and cell movement: ultrastructural studies on the rat 13762 mammary carcinoma and Walker carcinoma. AB - The aim of this study was to determine whether tumor cells move actively through the linings of lymph node sinuses. Using 13762 carcinoma in F344 rats, and Walker carcinoma in Wistar rats, 20 X 10(6) tumor cells were injected into the footpad, and the ipsilateral popliteal lymph node examined by transmission electron microscopy. The same tumors were examined by making standard cell spots on plastic or glass surfaces, and examining these by phase and reflection contrast microscopy, fluorescent microscopy after anti-actin and phallacidin staining and transmission electron microscopy. The 13762 cells do not migrate through the lining of the lymph node sinusoid, nor move actively in vitro. Ultrastructural appearances of the Walker rat carcinoma cells suggest that they move actively through the sinus lining. After 24 h in vitro the Walker rat carcinoma cells in the centre of the spot are adherent to the surface. There is some movement of the edge of the sheet, and individual tumor cells at the edge of the sheet move actively and independently. We conclude that the Walker rat carcinoma invades the lining of the lymph node sinusoid by active cell movement, and the 13762 carcinoma does not. PMID- 4042462 TI - Enhancement of in vitro chemotherapeutic activity by dimethylsulfoxide. AB - The effects of the differentiation-inducing polar solvent dimethylsulfoxide (DMSO) on the in vitro response of murine hepatocarcinoma cells to cisplatinum, BCNU, and melphalan were investigated using the sister chromatid exchange (SCE) and cell survival assays. Growth of cells in medium containing 2 per cent DMSO enhanced drug-induced SCEs and cell kill. In order for the enhancement to occur, cells had to be exposed to DMSO for at least 48 h prior to drug treatment. The presence of DMSO during drug treatment did not affect cell response to the three chemotherapeutic agents. The enhancement of chemosensitivity was eliminated within 24 h of DMSO removal. These data suggest that the differentiation-inducing polar solvents may provide antineoplastic benefits when administered in combination with standard chemotherapeutic agents. PMID- 4042464 TI - An image analysis system for the quantification of invasion in vitro. AB - We have tested the value of a computer-assisted image analysis program for the quantitative study of invasion in vitro using experiments that were previously described semi-quantitatively. Mouse fibrosarcoma cell (MO4) aggregates were confronted with precultured fragments of embryonic chick heart in organ culture. Confronting pairs were fixed after 1, 2, 3 and 4 days, and processed for paraffin sectioning and immunostaining with an antiserum against chick heart. The image analysis system allowed separate quantification of two aspects of invasion, namely, occupation of the heart tissue by MO4 cells and degeneration of the invaded heart tissue. Complex combination of occupation and invasion added a qualitative aspect of invasion that has not been described previously and that revealed qualitative differences in invasion under various circumstances. PMID- 4042463 TI - Expression of abl and other oncogenes is independent of metastatic potential in Abelson virus-transformed malignant murine large cell lymphoma. AB - The role of oncogene expression in tumor metastasis was examined using the Abelson leukemia virus-transformed murine large cell lymphoma RAW117. Cell sublines of low and high metastatic potential expressed equally abl oncogene coded mRNA and its phosphoprotein product p160, and the capacity of p160 to become autophosphorylated with gamma-[32P]ATP was the same among low and high metastatic cells. The expression of other oncogene-coded mRNAs (fos, myc, myb), if present, was also similar in low and high metastatic RAW117 cells. Although oncogene expression is thought to be important in initiating, and in some cases maintaining, the transformed phenotype, its expression in RAW117 lymphoma cells appears to be unrelated to metastatic phenotype. PMID- 4042466 TI - Postoperative exercise rehabilitation benefits children with congenital heart disease. AB - Physical fitness was assessed in children with congenital heart disease using seven tests designed to measure cardiovascular endurance, strength, flexibility and co-ordination. Test scores for age-matched healthy children were significantly higher than preoperative scores for patients. Postoperatively, the patients were divided into a control group and a physical training group. The training group was subsequently divided into compliant and non-compliant subgroups. Patients who complied with a simple six-week home program of physical activity training after surgery improved their test scores significantly (p less than .001) and were not significantly different from normal children. The scores of the non-compliant group remained below normal (p less than .01). When retested six months postop, the scores of all patient groups had improved; however, while there was no significant difference between the healthy and compliant groups, the scores of the non-compliant and control groups remained significantly below those of the healthy children (p less than .01). PMID- 4042465 TI - Theophylline pharmacokinetics in adolescent females following coadministration of oral contraceptives. AB - The influence of 3-9 months of combined low dose oral contraceptives on theophylline pharmacokinetics was studied in 10 adolescent females (age 15-18 years, mean +/- SD 17 +/- 1) and compared to 10 age-matched control subjects (age 13.8-19 years, mean +/- SD 16.5 +/- 1.6). The distribution volume (0.44 +/- 0.06 L/kg in control vs. 0.44 +/- 0.09 L/kg oral contraceptive group), total body clearance (0.78 +/- 0.13 ml/kg/min vs 0.78 +/- 0.18 ml/kg/min) and elimination T 1/2 (402 +/- 78 min vs. 409 +/- 126 min) were identical in the two groups. It appears that during the first 3-9 months of low dose oral contraceptive treatment, these steroids do not alter the pharmacokinetic behaviour of theophylline in adolescent females. PMID- 4042467 TI - A prospective serial study of the effects of radiotherapy on semen parameters, and hamster egg penetration rates. AB - Cancer patients were studied before radiotherapy (RT) and at regular intervals after treatment (1, 3, 12, 24, 36, 48 months) to determine the effect of radiotherapy on semen parameters and sperm function as assessed by the hamster egg penetration assay. The cancer patients received testicular radiation doses of 0.4 to 5.0 grays (40 to 500 rads). The pre-radiotherapy semen profile varied considerably but in general the profile was poor: 7/11 men had a sperm concentration less than 20 X 10(6)/ml and a total count of less than 50 X 10(6), while the hamster egg penetration rates were also very low with a mean of 5% (range 0% to 15%). This is the first study demonstrating that sperm function as well as sperm concentration is impaired in cancer patients pre-radiotherapy. At 3 and 12 months post-radiotherapy, 8/11 men were azoospermic. By 24 months 8/11 were producing sperm although only 2 had hamster egg penetration rates greater than 15%. All men studied at 36 months (4) and 48 months (3) post-radiotherapy had recovered spermatogenesis but hamster egg penetration rates were still poor. There was a highly significant inverse correlation between testicular radiation dose and subsequent sperm concentration and hamster egg penetration rates. PMID- 4042468 TI - Fractures of the lateral process of the talus. AB - A retrospective review of nine patients with fractures of the lateral process of the talus indicates that a substantial portion of patients will have persistent symptoms if the fracture is not diagnosed and appropriately treated soon after the injury. When a patient is evaluated for the symptoms of a "sprained ankle," these fractures are often overlooked on the initial roentgenograms. If untreated, these fractures often fail to heal, and persistent pain over the lateral aspect of the ankle following an inversion injury should be investigated for the possibility of this diagnosis. Prompt treatment of acute fractures appears to lead to the best result. Nondisplaced fractures heal well in a short-leg cast, with six weeks of immobilization. Large displaced fracture fragments require surgical treatment: single large fragments should be reduced and internally fixed, and large comminuted fragments should be excised. PMID- 4042469 TI - Clinical application of computerized axial tomography (CAT) scanning of calcaneus fractures. AB - CAT scanning of calcaneal fractures with the 30 degree coronal or the transverse plane provides useful information not available on conventional roentgenograms. Joint alignment, displacement of fragments, and the integrity of the medial wall are key factors in deciding whether surgical reconstruction is indicated and what surgical approach to use--medial, lateral, or both. Examples of such information obtained on eight patients with calcaneal fractures is reported comparing CAT scan results to conventional roentgenograms. CAT scans can be used also with the foot immobilized in a cast. PMID- 4042470 TI - Open reduction in depressed fractures of the os calcis. AB - Fifty-two patients with subtalar joint involvement secondary to os calcis fractures have been treated with a surgical technique designed by George F. Pennal. There were 23 tongue-type fractures and 33 joint depression fractures in this series. All were treated by open reduction and internal fixation, and occasionally also by bone grafting. Patients have been followed from two to seven years from the time of their injury, and the results indicate that 39 of the patients are relatively symptom-free and doing the same work as they had done prior to their injury. Nine patients have required some modification of their work, and four patients were classified as failures. Treatment of depressed fractures of the subtalar joint by this method produces relatively predictable results. PMID- 4042471 TI - The operative treatment of fractures of the os calcis. AB - Displaced intra-articular fractures of the body of the os calcis are notorious causes of significant and prolonged disability. Treatment recommendations for these injuries have varied widely. An understanding of the anatomy and pathomechanics of the injury is important in treatment selection. Tongue-type and joint depression-type calcaneal fractures are subdivided on the basis of relations of the primary fracture line to the posterior facet. Treatment regimens are also based upon these relations and fracture classification. Choice of surgical approach depends upon the fracture pattern, including secondary comminution. The goal of operative treatment is to reestablish articular congruency, calcaneal width, and early range of motion. Operative treatment can be recommended for fractures that can be accurately reduced and rigidly transfixed. Nonoperative treatment is recommended for those fractures where accurate reduction is unattainable. PMID- 4042472 TI - Patient selection for lumbar laminectomy and discectomy with a revised objective rating system. AB - A revised objective rating system for patient selection for lumbar laminectomy and discectomy in the treatment of disc herniation is presented. Based on the severity of the findings within each of four categories (neurologic signs, root tension signs, myelogram or CT scan findings, and psychosocial environment), numerical scores are derived. A maximum score of 25 points is available in each category, for a total of 100 points. The objective rating score was determined prospectively in 106 patients who were treated by laminectomy for lumbar disc herniation and who were evaluated at least one year after surgery. The rating score was highly predictive of the surgical result. Application of this system for patient selection would reduce reliance on much of the subjective interpretation of physical and radiographic findings. With appropriate patient selection, improved surgical results are possible. PMID- 4042473 TI - Histochemical and morphometric changes in muscles of stroke patients. AB - There is little information on the muscle fiber changes or the fiber type affected in supraspinal hemiplegia. Muscle biopsy specimens from 20 patients with stroke, obtained during orthopedic reconstruction, were examined by modern histochemistry. Atrophy was present in all of the muscles, affecting Type 1 fibers in 100% and Type 2 fibers in 95% of the patients. Type 2 atrophy was more severe than Type 1 atrophy. Group atrophy and fiber type grouping, present in 40%, seemed related to peripheral nerve or root damage. Hypertrophy of Type 1 fibers was present in 45%, associated with Type 2 hypertrophy in 15%. Although diffuse morphometric atrophic seemed not to correlate with the level of motor activity in this group of 20 patients, hypertrophy appeared related to activity. Hence, efforts to mobilize and rehabilitate stroke patients cannot prevent atrophy of some fibers, they seem to stimulate a hypertrophy not seen in inactive patients. PMID- 4042474 TI - A modified lateroanterior approach in operations for hip arthroplasty. AB - When straight and bulky instruments are used in operations for hip arthroplasty, exposure of the hip is not always wide enough, and extensive tissue dissection or a trochanteric osteotomy may be necessary. To avoid this and yet obtain wide exposure, a modified lateroanterior Ling approach was used in 40 consecutive operations for hip arthroplasty. The continuity between the gluteus medius and the vastus lateralis is preserved. These muscles are split, and the anterior attachments are decorticated from the greater trochanter, forming an osteotendinous flap that is displaced ventrally, exposing the anterior capsule of the hip. This approach, causing the least disturbance to the abductor mechanism, offers the advantages of wide exposure and, postoperation, a stable and easily activated hip. PMID- 4042475 TI - Intra-articular osteochondromas of the hip joint in a child with multiple osteochondromas. Case report. AB - A child five and one-half years old with multiple osteochondromas presented with symptoms mainly affecting her right hip. Several intra-articular osteochondromas had formed about the femoral neck and acetabulum. The osteochondromas were removed, and hip development appears to be normal over a four-year follow-up period. PMID- 4042476 TI - Legg-Calve-Perthes disease in a family: genetic or environmental. AB - This is a case report of a family in which Legg-Calve-Perthes disease (LCPD) occurred in four members. All the patients were male and between the ages of three and eight years. This unusually high incidence in one family raises questions about the genetic versus the environmental factors in the etiology of LCPD. PMID- 4042477 TI - Hemophilus influenzae infection of a total hip arthroplasty. AB - Hemophilus influenzae is an uncommon, seldom considered pathogen of septic arthritis in adults. H. influenzae seems not to have been reported in association with a total joint infection. The majority of previously reported H. influenzae cases have been associated with joint trauma or preexisting joint disease. A 63 year-old woman with a late hematogenous infection due to H. influenzae of a total hip arthroplasty was treated by surgical debridement and appropriate antibiotics. In a short-term follow-up evaluation of one year, this treatment was successful in allowing retention of the prosthesis and return to satisfactory function. PMID- 4042478 TI - Primary knee ligament repair--revisited. AB - There were 4710 knee sprains resulting from skiing in the four Aspen ski areas between 1976 and 1979. Twenty percent of the patients (942) had complete tears. Of these, 302 elected to remain in Aspen for treatment. All were treated by primary ligament repair without augmentation. These cases were evaluated an average of 42 months after injury. Patients with isolated tears of the medial collateral ligament were found to be doing well; virtually all of them had returned to preinjury activity levels. Thirty-six percent of the isolated anterior cruciate repairs were rated failures, and 43% of the combination ACL-MCL injuries had failed because of anterior cruciate deficiency. Twenty-nine percent of the ACL and ACL-MCL injuries had meniscal tears. Cases that included meniscectomy had a failure rate twice as great as those in which the meniscus was preserved. The results following repair of anterior cruciate tears were not acceptable, and augmentation was indicated. Primary repair of medial collateral ligament tears produced excellent results. Meniscal tears were frequent in association with ligament disruption. Ligament repairs were less satisfactory when meniscectomy was performed at the time of the repair. PMID- 4042479 TI - Antalgic maneuvers during walking in men with unilateral knee disability. AB - The gait of men with unilateral knee disability has not been quantified previously. Interrupted-light photography was used to quantify the gait abnormalities of 35 men whose major disability was unilateral knee pain. The following antalgic maneuvers were found to be common to the gait of these patients: slow and uneven forward progression with lateral lurching toward the painful side, asymmetry in stride and temporal components, and abnormalities in the displacement patterns of most body segments. Subnormal knee motion was found during the stance and swing phases. Because treatment of patients with knee problems is usually directed toward pain relief, an understanding of how pain affects walking performance is important to the clinician when assessing a patient's problem. PMID- 4042480 TI - Infected total knee arthroplasties. AB - Thirty infected total knee arthroplasties were investigated in 29 patients over an average interval of 42 months. Eleven infections began in the immediate perioperative period. Six developed from postoperative wound-healing problems. The remainder were late infections. Staphylococcus was found in 16 infections, gram-negative agents in five, mixed organisms in five, and other gram-positives in four. Sixteen knees were arthrodesed, six knees were treated by retention of the components, and two above-knee amputations and one resection arthroplasty were performed. Five patients had two-stage revisions to new components. Evidence of persistent infection was present in three arthrodeses, two retained arthroplasties, and one knee that was revised. Perioperative infections were associated with staphylococcal organisms and responded less favorably to conservative treatment. The failure of primary wound healing demands immediate measures to obtain skin coverage. Retention of the arthroplasty components is possible only in selected patients. PMID- 4042481 TI - Bone scanning in the assessment of patellar viability following knee replacement. AB - In an attempt to diagnose avascular necrosis (AVN) of the patella, a potential complication of the surgical procedure, 99mTc-MDP bone scanning was performed pre and postoperation in 37 patients treated by 41 total knee arthroplasties. The normal immediate postoperative scan should demonstrate increased radionuclide uptake in the patella when compared to preoperative scans. Decreased uptake was seen in four cases in the early postoperative period. This latter group was believed to be at risk for osteonecrosis and stress fracture of the patella. For this reason, prophylactic restriction of activity was instituted, with subsequent return of normal radionuclide uptake in the patella. Bone scanning provides an effective method of early diagnosis of patients at risk for the development of AVN and secondary patellar fractures following total knee arthroplasty. PMID- 4042482 TI - Bilateral total knee arthroplasties. Comparison of simultaneous (two-team), sequential, and staged knee replacements. AB - Simultaneous and sequential operations for bilateral total knee arthroplasties (TKA) for arthritis were examined for determination of the relative safety of each method. The postoperative morbidity was analyzed in three groups of patients who were similar with respect to age, sex, type of arthritis, preoperative range of motion, and postoperative management. Group I (22 patients) had both knees replaced simultaneously under one anesthesia. Group II (26 patients) had two operations staged about 17 days apart during a single hospitalization. Group III (20 patients) had TKA in two hospitalizations with the operations separated by about eight months. In this small series of cases there were fewer complications and a significantly shorter hospitalization in the group having simultaneous bilateral TKA. PMID- 4042483 TI - Strength of union in human tibial shaft fracture. A prospective study of 104 cases. AB - In a consecutive prospective series of 104 tibial shaft fractures, the strength at the site of union was observed by a noninvasive technique at regular intervals. Eighty-one patients were male and 23 were female. Six fractures were open, and 13 patients had multiple injuries. The primary treatment was conservative with cast immobilization in 86 patients, external fixation by a quadrilateral system in 14, and open reduction and internal fixation in four. A measure of the strength of union is obtained by calculating a quotient between induced deflection between the fracture fragments and the applied bending moment. By plotting this quotient against time-since-injury, a curve describing the changes in stability can be constructed. With this curve it is possible to define united fracture and normal union, and the differentiation between delayed union and true nonunion is possible. Time-to-union in all 104 patients was 16 +/- 15.2 weeks. In 14 with delayed union, surgical measures intended to promote union could be avoided because repeated measurements indicated progressive increase in stability. Bone grafting was performed in 13 fractures for treatment of nonunion. Statistical analysis based on objective measurement of stability failed to identify a specific factor responsible for delayed union or nonunion. PMID- 4042484 TI - Accuracy of radiologic assessment of tibial shaft fracture union in humans. AB - In a series of 208 tibial shaft fractures, 166 were treated nonoperatively, and of these, 157 had an uncomplicated course of healing. The process of union was followed by repeated noninvasive measurements of fracture stability. Full unprotected weight-bearing was permitted when stability measurements indicated solid union. A group of 127 fractures was evaluated by seven senior radiologists for assessment of the stage of union on anteroposterior and lateral radiographs exposed at the time of measurements of stability. The time for assessment ranged from four to 46 weeks. The radiologic assessment was difficult to correlate to the stability of union; in 55% of unstable fractures, the films pointed to satisfactory union. Of the 93 fractures that were mechanically stable, the films suggested that no union had been achieved in 44%. The probability of a correct radiographic evaluation of stage of union was approximately 0.5. The period required to achieve solid union after tibial shaft fracture is relatively long and unpredictable. Definitions of stage and progress of union are controversial. Conventional roentgenographic examinations as a means of assessing the stage of union are generally inconclusive. PMID- 4042485 TI - Foreign body granuloma of bone secondary to silicone prosthesis. A case report. AB - The clinical experience with silicone rubber arthroplasties has been unremarkable except for sporadic reports of reactive synovitis in the form of a foreign body giant cell inflammation. A 21-year-old man is the first known instance of a large lytic lesion in a bone articulating with a silicone implant. PMID- 4042486 TI - A new evaluation of gross pathologic changes and concepts of rheumatoid articular cartilage degeneration. AB - Fifty-one knees in 32 ambulatory patients with rheumatoid arthritis were examined arthroscopically, enabling direct observation of the pattern of gross degeneration at the joint line and synovial chondral junction. Four distinct stages of pannus ingrowth and meniscal degeneration were observed, which correlated with the extent of articular destruction. Significant direct pannus invasion of articular cartilage was not observed in any stage in the ambulatory mobile rheumatoid knee. Stage I is comprised of synovial hypertrophy. Stage II shows invasive pannus affecting meniscal surfaces. Stage III exhibits meniscal tearing and production of abrasive debris. Stage IV is end-stage loss of meniscus and denudation of articular surfaces. Articular cartilage destruction was not observed in patients without visible meniscal degeneration or pannus ingrowth but was observed in knees without roentgenographic erosion or joint space narrowing. A new evaluation of articular degeneration in the ambulatory mobile rheumatoid knee is based on mechanical destruction by torn menisci and free debris observed by arthroscopy. PMID- 4042487 TI - Hip arthroplasty surgery in Manitoba: 1973-1978. AB - A review of all (1279) total hip arthroplasties in the Province of Manitoba, Canada, from 1973 to 1978 demonstrates an increase in the number of operations except in the very elderly. Six-week operative mortality was decreased from 2.4% to .6%, and time spent in the hospital has decreased from 54 to 40 days. Utilization of medical services by patients before and after surgery, as recorded by the Manitoba Health Services Commission, enables identification of all serious postoperative complications. Two years after surgery, 95.2% of patients were alive, and 16% had a contralateral hip arthroplasty. Fourteen patients (2.7%) required revision surgery within two years; 20 patients (4%) were readmitted to the hospital with other surgical complications, including trochanteric bursitis, osteomyelitis, pulmonary embolism, and so forth. Visits to physicians for arthritis-related problems and to chiropractors decreased in the two years after surgery compared with the two years before. PMID- 4042488 TI - A modified technique for the fixation of pathologic fractures in the lower femur. AB - Intramedullary nail fixation augmented by the pressure injection of methylmethacrylate was investigated by use of bovine femora. In this technique, the nail is first placed in its final desired position; cement is then injected with a conical-tipped syringe through a distal drill hole into the medullary canal around the nail. This method was compared with the conventional technique of first placing the cement into the medullary canal and then driving the nail into position. Calf femora were used to compare the cement pressures generated, the shear resistance at the bone/cement interface, and the contour of the endosteal cement surface produced by the two cementing techniques. Significantly higher bone/cement interface pressures were generated by the injection of cement. Shear resistance at the bone/cement interface, investigated by push-out tests, revealed no significant difference between the two techniques. Dissolution of the specimens in nitric acid produced a methylmethacrylate cast of the endosteal surface, thus revealing the pattern of cement penetration into endosteal bone. The cement surfaces made by the injection of cement revealed characteristics of superior fixation and penetration compared to those made by the conventional method. The injection of cement for pathologic long-bone fractures is safer than the conventional method, is less susceptible to intraoperative complications, and offers satisfactory fixation. PMID- 4042489 TI - Parathormone, calcitonin, and vitamin D metabolites during normal fracture healing in geriatric patients. AB - In order to study the role of calcium-regulating hormones during callus formation in elderly patients, serum levels of parathormone (PTH), calcitonin (CT), 25 hydroxyvitamin D [25-OH-D], 1,25-dihydroxyvitamin D [1,25(OH)2D], 24,25 dihydroxyvitamin D [24,25(OH)2D], and calcium (Ca) were determined in 41 patients with fractures of long bones, primarily hip fractures. The parameters were measured on admission and after eight weeks. There were almost no changes in hormone serum levels during bone repair, except for a decrease in serum levels of 1,25(OH)2D from 25.3 +/- 2.3 pg/ml on admission to 21.0 +/- 2.0 pg/ml eight weeks later (p less than .001). Patients with fractures compared to normal elderly humans have lower serum levels of PTH (0.99 +/- 0.06 ng/ml versus 1.88 +/- 0.34 ng/ml; p less than .001), 25-OH-D (10.7 +/- 1.0 ng/ml versus 17.1 +/- 1.8 ng/ml; p less than .001), and Ca (9.1 +/- 0.1 mg% versus 9.7 +/- 0.1 mg%; p less than .001) and higher serum levels of 1,25(OH)2D (25.3 +/- 2.3 pg/ml versus 17.1 +/- 2.3 pg/ml; p less than .001). Female patients have lower serum levels of 24,25(OH)2D compared to males (1.65 +/- 0.15 ng/ml versus 2.06 +/- 0.29 ng/ml; p less than .05). A similar trend was noted in serum CT levels during callus formation (0.12 +/- 0.02 ng/ml versus 0.16 +/- 0.02 ng/ml; p less than .05). Patients with subcapital fractures of the femur have significantly lower serum levels of all vitamin D metabolites on admission, compared with patients suffering from extracapsular fractures.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4042490 TI - Cefamandole levels in serum and necrotic bone. AB - Seven patients with chronic osteomyelitis were treated by surgical debridement. Cefamandole was administered intravenously before surgery. During the debridement, cefamandole concentrations were measured in serum and necrotic bone. Although adequate levels of antibiotic were achieved in the serum, minimal or no concentration of antibiotic was found in the necrotic bone. There was only minimal penetration of cefamandole into necrotic bone. PMID- 4042491 TI - Periosteal stress-induced reactions resembling stress fractures. A radiologic and histologic study in dogs. AB - An external callus is always associated with so-called stress fractures, but a fracture line cannot always be demonstrated by radiologic means. In such instances it is assumed that an undisplaced fracture or microfracture must nevertheless exist for an external callus to form. In this experimental study, 18 beagles were immobilized in a shoulder spica for periods of time ranging from 6 to 32 weeks and then remobilized. At the time of sacrifice, which varied from four to 28 weeks after remobilization was started, eight showed on radiographs an external fusiform bone formation on the distal metacarpal metaphysis during the remobilization period without evidence of a fracture line. Serial histologic examination, in seven metacarpi, also failed to reveal the presence of any break in the bone's continuity. Although this does not exclude the accumulation of microdamage (mechanical fatigue) at such sites, there is sufficient evidence that the circumscribed periosteal reaction occurred at a site of increased stress in the absence of an actual fracture. Consequently, this condition is called a periosteal stress-induced reaction. PMID- 4042492 TI - Development of nonunions in the rat fibula after removal of periosteal neural mechanoreceptors. AB - Periosteal proprioceptive nerve receptors may act as mechanoreceptors of long bones during adaptive remodeling after fracture. They may also contribute to the mechanisms of coordinated functional activity of fractured limbs and thus inhibit harmful overloading of fracture callus. The area of proprioceptive nerve receptors around the distal part of the rat fibula was stripped surgically, and a standard fracture of the fibular shaft was produced. Animals failed to unite their fractures and developed mainly atrophic nonunions. Atrophy of ununited fragments was due to osteoclastic bone resorption. Atrophy of the bone fragments was aggravated if the legs were also subjected to sciatic denervation. Sciatic denervation alone, without removal of receptors, did not interfere with the union of fractures. The results indicate that the area of proprioceptive receptors in the rat tibiofibular bone is critical for the healing of fibular fractures. Because the effect on bone healing of receptor removal was not inhibited by sciatic denervation, the effect was not transmitted through spinal pathways of the sciatic nerve. The development of nonunions could not be explained by the surgical trauma alone. Aggravation of fibular atrophy by sectioning of the sciatic nerve suggests that some neural elements are associated with the phenomenon, either directly or indirectly through neuromuscular function. PMID- 4042493 TI - Role of synovial fluid cells in the healing of flexor tendons. AB - A 1-cm segment of repaired rabbit flexor tendon was first subjected to 10,000 rads of x-radiation and then placed in the synovial cavity of a rabbit's knee joint. Macroscopic examination revealed healing at the repair site and rounding of the tendon ends without adhesions. Light- and electron-microscopic studies revealed cells resembling fibroblasts at the repair site and the periphery laying down collagen. Healing of this irradiated nonviable tendon was brought about by the cells present in the synovial fluid. PMID- 4042494 TI - Trabecular bone strength profiles at the ankle joint. AB - The mechanical strength of trabecular bone at the ankle joint was studied in ten amputation specimens by means of multiple penetration tests. Tibial bone was considerably weaker than talar bone (40% on average). An area of peak bone strength located posteriorly and medially to the center of the joint was found in most joints. The variation of bone strength with the depth from the surface was studied by comparing five successive 2-mm levels. At the tibia there was a statistically significant decrease of bone strength from the first to the second level. At the talus, bone strength increased at first, then decreased significantly. The absolute values of strength recorded suggest that in a substantial number of the joints studied, the resection surfaces--especially at the tibial side--might be too weak to support the loads imposed by current prosthetic designs. PMID- 4042495 TI - Operative arthroscopy of the ankle. Three years' experience. AB - This is a preliminary report on 15 cases of surgical arthroscopy of the ankle performed between 1979 and 1983. Age range of the patients was from 14 to 35 years. Follow-up examinations were performed between six months and two and one half years after surgery, with an average of 14 months. The indications were pain or clicking sensations accompanied by painful limitation of motion for an average of three months. Chondral and osteochondral fracture of the talar dome were observed in nine cases; chondral and osteochondral lesions of the tibial plafond in two cases; osteochondral loose bodies in two cases and; posttraumatic adhesions or arthritis was found in three cases. Treatment consisted of debridement of osteochondral lesions, removal of loose bodies, curettage, drilling, synovectomy, and abrasion of the subchondral bone. The results were assessed subjectively and objectively. Satisfactory overall results were obtained in 85% of the cases. There were no major complications. This study suggests that arthroscopic surgery has a definite role in the management of intra-articular lesions of the ankle. The results are reproducible if the arthroscopic surgeon pays proper attention to the anatomy of the area and is familiar with the use of different arthroscopic portals. PMID- 4042496 TI - Internal compression arthrodesis of the ankle. AB - Eight patients with disabling tibiotalar arthritis (one patient with a supramalleolar nonunion) were treated by arthrodesis. The procedure in all of these patients consisted of internal compression obtained by bone plates and the application of a bilateral tension device. A bilateral surgical approach was used. No bone grafting was required. This study compares two groups immobilized for ten and three weeks, respectively. In both groups, the procedure invariably produced union with excellent cosmesis, few complications, and good function. PMID- 4042497 TI - Corrective lengthening osteotomy of the fibula. AB - Widening of the ankle mortise following fracture can be a subtle diagnosis requiring special radiographs to fully appreciate the extent of shortening and rotation of the fibula. Once this fibular shortening has been recognized, a lengthening and rotational osteotomy can be conducted with use of a special compression/distraction device and bone graft. A series of 23 cases demonstrates that reconstructive lengthening osteotomy is well worthwhile when there is absent or minimal osteoarthritic change, irrespective of the time from the original injury. PMID- 4042498 TI - Measurement of the motion range in the loaded ankle. AB - In an easily practicable method of measuring the motion range in the ankle under load, the patient is asked to put his foot on a 30-cm-high stool and then lean forward as much as possible without lifting his heel from the supporting stool. In this position the knee is flexed and the greater part of the body weight is on the examined foot. Dorsal extension is then measured with a protractor as the angle between the support line of the foot and the long axis of the leg. The loaded plantar flexion is measured in the same position but with the heel raised as much as possible. In a study of 317 healthy ankles, this method was found to give greater and more reproducible values than measuring on unloaded ankles in sitting or supine positions. Measurements of the loaded dorsal extension were also made on radiographs of 66 healthy ankles. The mean value was 32.5 degrees; the mean talar forward tilt was 5.0 degrees. In normal daily life, at least 10 degrees are required; for performing athletics and sports activities, a loaded dorsal extension range of 20 degrees-30 degrees is necessary. PMID- 4042499 TI - Changes in tibiotalar joint contact areas following experimentally induced tibial angular deformities. AB - Six cadaveric legs were stripped of all soft tissue excluding the interosseous membrane and the tissues about the ankle joint and foot. Angular deformities were simulated in all planes to a maximum of 15 degrees for proximal, middle, and distal third levels following tibial resection and same-level fibular osteotomy. Anterior ankle arthrotomies allowed exposure to the tibiotalar joint so that contact area could be measured with pressure-sensitive film inserted between the tibia and talus. An angular deformity of 15 degrees or less produced no significant alteration in the contact area of the ankle joint for proximal and middle third tibial levels. Distal tibial deformities showed a dramatic change in the contact area, with as much as a 42% decrease in contact area for anterior deformities. The contact shape for distal third angular deformities of 10 degrees and 15 degrees in all planes also tended to elongate, with a shift to more lateral contact noted. Although minor degrees of angular malalignment had little effect on ankle contact for proximal and middle third levels, it would appear that distal third deformities produce a greater change in ankle joint contact; thus, fractures at the distal level should be managed to minimize the possibility of tibial malalignment. PMID- 4042500 TI - Long-term results of displaced talar neck fractures. AB - Of 36 fractures of the talar neck without comminution of the body, eight were undisplaced, treated closed, and 28 were displaced and treated by open reduction. Twenty of the operations were less than 12 hours after injury. Nineteen of 20 were performed through a medial approach, six with a medial malleolar osteotomy. The long-term results were evaluated by a standard rating system based on classification by the fracture. A protective brace was developed for non-weight bearing in two patients with complete avascular necrosis, and ankle protection with weight-bearing in ten with partial necrosis. Prompt open reduction and internal fixation, malleolar osteotomy, and protected weight-bearing are recommended in selected cases. PMID- 4042501 TI - Operative treatment of displaced talus fractures. AB - The talus is a bone with unique biomechanical features and vascular supply. Displaced fractures of the talus, therefore, frequently create problems of proper management. Forty-one severe talar fractures were treated operatively. The incidence of avascular necrosis was relatively low in this series (16%), and all of these were of Type III and IV fractures of the Marti-Weber classification. Type IV fractures were successfully treated by arthrodesis per primam, and suggested that fusion may be the indicated method of treatment in these severe injuries. Fusion of the tibiotalar joint has been used to encourage revascularization and to preserve the important function of the subtalar joint. In all other fracture types with dislocation, anatomic reduction is performed to restore joint congruity and encourage maintenance of talar dome viability. Painstaking postoperative management is important for the complete restoration of function. PMID- 4042502 TI - Eighty-five talus fractures treated by ORIF with five to eight years of follow-up study of 69 patients. AB - Four types of talus fractures can be distinguished and the prognosis predicted on the basis of vascular patterns before and after injury. Early decompression of the soft tissues or anatomic reduction by closed or (if not possible) open methods is indicated. Stable fixation by lag screws and functional aftertreatment help to improve the prognosis. The late results with reference to necrosis, posttraumatic arthrosis, secondary arthrodesis, and functional outcome show that open reduction and internal fixation, applied early, can produce better functions than was heretofore thought possible. Special emphasis is placed on careful indications, operative techniques, and postoperative treatment--particularly the time of partial weight-bearing with a caliper brace. PMID- 4042503 TI - The utility of adrenal scintigraphy in Cushing's syndrome and hyperaldosteronism. AB - Thirty-three adrenal scintigrams in 30 patients were reviewed to determine the utility of this noninvasive imaging technique. It was found to be very accurate in distinguishing bilateral from unilateral hyperfunction in patients who have clinical and biochemical evidence of adrenal cortical hyperfunction. The technique proved correct in 12 of 12 cases of Cushing's syndrome and 14 of 19 cases of hyperaldosteronism. Specific clinical questions were also answered in three miscellaneous cases. PMID- 4042504 TI - Enterogastric reflux detection with technetium-99m IDA. AB - A Tc-99m IDA scan was performed in a patient with severe alkaline esophagitis subsequent to a Billroth I gastroenterostomy. The scan showed enterogastric reflux simultaneously with gastroesophageal reflux of bile. The study was recorded in a computer and the reflux quantitated. PMID- 4042505 TI - The use of technetium-99m sulfur colloid in the detection of patent processus vaginalis in patients on continuous ambulatory peritoneal dialysis. AB - Continuous ambulatory peritoneal dialysis (CAPD) is commonly used in patients with renal failure as an alternative to hemodialysis. A not infrequent complication is scrotal swelling due to bowel or fluid passing through a patent processus vaginalis secondary to increased abdominal pressure. A radionuclide study using Tc-99m sulfur colloid is a safe and simple method to determine if this complication is present or may be used as a pre-CAPD screening procedure. PMID- 4042506 TI - "Streaming" in portal vein. Its effect on the spread of metastases to the liver. AB - Fifty-five consecutive patients with colorectal carcinoma and hepatic metastases on the Tc-99m sulfur colloid liver/spleen scan (TSC) were evaluated to see if the pattern of spread of colorectal metastases was affected by the venous drainage of the primary site. The results suggest that significant streaming probably exists in the portal vein and the spread of metastases to the liver is affected by it. This information has a potential clinical implication in terms of diagnostic workup and chemotherapeutic infusions. It also supports the speculation that a streaming effect exists in humans. PMID- 4042507 TI - Co-existent parathyroid adenoma and thyroid carcinoma. Nonspecificity of dual tracer parathyroid imaging for parathyroid lesions. AB - Dual tracer parathyroid imaging (DTPI) using Tc-99m and TI-201 has a reported sensitivity of 92% for the detection of parathyroid adenomas. A patient with biopsy-proven parathyroid adenoma as well as papillary thyroid carcinoma is presented. To date, this is the first such case ever to be reported and implies that DTPI, although a sensitive diagnostic modality for parathyroid adenoma detection, is not specific. The diagnosis of primary hyperparathyroidism has recently been established more frequently than in the past due to detection of elevated serum calcium levels on routine blood samples, relatively sensitive parathormone (PTH) assays, and noninvasive imaging modalities such as nuclear medicine, CT scanning, and ultrasonography. At our institution, we have successfully detected the location of parathyroid adenomas in many cases, using the dual tracer method with TI-201 and Tc-99m, confirmed at surgery. We present a case of primary hyperparathyroidism in which two distinct lesions were detected by nuclear imaging: one lesion was proven at surgery to be a parathyroid adenoma, while the other represented thyroid carcinoma. PMID- 4042508 TI - Thallium-201 myocardial perfusion imaging in myocarditis. AB - TI-201 myocardial perfusion imaging was performed in six patients with clinically documented myocarditis. Each case manifested electrocardiographic abnormalities with elevation of serum cardiac enzymes and no significant stenosis of the coronary arteries observed on angiogram. Resting TI-201 images were visually assessed by three observers. Focal perfusion defects were observed in three cases (50%), among which two showed multiple perfusion defects. Emission computed tomography using TI-201 clearly delineated multifocal lesions in the first case. On the other hand, no significant perfusion defects were noted in the remaining three cases. Thus, myocarditis should be considered as one of the disease entities that may produce perfusion defects on TI-201 myocardial imaging. PMID- 4042509 TI - Photopenia of a hemithorax on technetium-99m HMDP bone scintigraphy resulting from massive pleural effusion. AB - Accumulation of Tc-99m labeled phosphonate bone scanning agent in a pleural effusion usually shows a mild and diffuse increase in radioactivity of the involved thorax. A malignant neoplasm was thought to account for this accumulation. The photon deficiency of the hemithorax on Tc-99m HMDP bone scintigraphy was shown in a case of massive pleural effusion, which was proved by autopsy to be due to metastatic breast carcinoma in the pleura. Two factors caused these scintigraphic findings: 1) a large amount of fluid in the pleural cavity caused photon attenuation; 2) the higher body background in the noninvolved hemithorax and other areas of the body was due to renal dysfunction resulting from chronic pyelonephritis. Whether the accumulation of the radiopharmaceutical agent in the pleural effusion was malignant or benign could not readily be distinguished. PMID- 4042510 TI - Focal pulmonary edema. Correlation with perfusion lung scan. AB - Pulmonary embolism is diagnosed by a mismatched perfusion-ventilation lung scan. The probability is increased further when there is an associated "hot spot" in the perfusion study caused by focal pulmonary edema. PMID- 4042511 TI - Bone image detection of lesions induced by self-administered anticoagulants. PMID- 4042512 TI - Bladder in the sac. PMID- 4042513 TI - Vertebral hemangioma. Radionuclide, radiographic, and CT correlation. PMID- 4042514 TI - Focal liver defect caused by hydatid cyst in the lung. PMID- 4042515 TI - Dual "hot spot" during combined hepatic imaging. PMID- 4042516 TI - Vesicocolonic fistula. PMID- 4042517 TI - Single-dose and steady-state pharmacokinetics of aminoglutethimide. AB - The oral pharmacokinetics of aminoglutethimide were determined in 17 patients receiving the drug therapeutically. The absorption of aminoglutethimide after oral intake was almost complete as judged by recovery of radio-labelled drug in the urine. The plasma half-life of the drug was markedly reduced (mean 43%) during multiple-dose administration as compared with a single dose, but only a moderate increase in total clearance (mean 26.9%) was observed. This finding was consistent with a significant reduction (mean 29.2%) in apparent volume of distribution (Vd) occurring during prolonged treatment. These alterations in drug distribution could also be demonstrated after a drug-free interval of 96 hours during treatment. The reduction in apparent volume of distribution could not be explained by altered plasma protein binding of aminoglutethimide, as evaluated by equilibrium dialysis experiments. PMID- 4042518 TI - Doxepin plasma concentrations in clinical practice. Could there be a pharmacokinetic explanation for low concentrations? AB - During therapeutic use of doxepin, we have often observed unexpectedly low doxepin plasma concentrations in patients on moderate dosages, e.g. 100 to 200mg daily. While non-compliance seemed the most likely explanation, we present the data for 6 patients in whom we considered non-compliance unlikely. The data can be explained by hypothesizing that in some patients, there is not a linear dosage plasma concentration relationship and that on a steady dosage, plasma concentrations are not always maintained. If these phenomena can be more carefully documented they may assume clinical importance; indeed for 2 of the patients studied the falling plasma concentrations on a steady dosage were associated with a recurrence of depression. PMID- 4042519 TI - Pharmacokinetic properties and bioavailability of methimazole. AB - The pharmacokinetics of methimazole following therapeutic doses were studied in healthy subjects, in thyrotoxic and hypothyroid patients before and after treatment to euthyroidism, and in patients with renal or hepatic insufficiency, using a highly sensitive gas chromatographic-mass spectrometric assay. Following intravenous administration of 10mg to healthy subjects, methimazole had an initial distribution half-life (t1/2 alpha) of 0.10 to 0.23 hours and an elimination half-life (t1/2 beta) of 4.9 to 5.7 hours. The absolute bioavailability after oral administration of 10mg methimazole in the fasting state was high, with a mean of 93%. The pharmacokinetic profiles showed small interindividual variations, although one of the hypothyroid patients had a rapid elimination half-life, in both the hypothyroid and euthyroid state (2.6 and 2.4 hours, respectively). The elimination rate was not enhanced in the thyrotoxic patients but was slightly prolonged in the hypothyroid patients. There was no influence of renal insufficiency, but a prolonged elimination half-life was observed in patients with hepatic failure, the prolongation being proportional to the degree of impairment. Thus, the pharmacokinetics of methimazole are relatively simple with small interindividual variations. In general, there are no pharmacokinetic reasons to adjust dosage in the treatment of thyrotoxicosis, except in the rare case of concomitant advanced hepatic insufficiency. PMID- 4042520 TI - Interactions between ethanol and oral contraceptive steroids. AB - We investigated the effect of oral contraceptive steroids (OCSs) on plasma ethanol disposition and tolerance to ethanol. Fifty-four healthy women between 18 and 40 years old were classified as light (31) or moderate (23) drinkers. Each group was further subdivided into controls (no OCS; 10 light, seven moderate drinkers), 30 or 35 micrograms estrogen OCS (14 light, 11 moderate drinkers), and 50 micrograms estrogen OCS (seven light, five moderate drinkers). Four of the subjects were studied on a second occasion, thus acting as their own controls with and without OCS use. All women were studied between days 14 and 21 of their pill/menstrual cycle. Plasma ethanol concentrations and two simple tests of motor function were measured for 6 hours after ethanol, 0.9 gm/kg in orange juice drank over a 30-minute period. The groups were well matched for age and weight. There were no significant differences between any of the six subgroups in mean peak plasma ethanol concentration, mean time to peak, mean AUC, or mean rate of ethanol disappearance. This was also the case for the four women who acted as their own controls. Analyses between those receiving high and low progestogen OCSs and between smokers and nonsmokers showed no significant differences. There was acute deterioration in functional performance as measured by two motor function tests in all subjects, regardless of OCS use. Moderate drinkers were significantly less functionally impaired than light drinkers whether with or without OCS use, indicating acquired tolerance. The mean degree of impairment and mean recovery time for both tests were significantly less in the OCS groups than in the control groups. The same trend was seen in the four women who were their own controls. Our results suggest that OCS use may induce some form of "tolerance" to ethanol. However, because there is no evidence of any change in ethanol disposition even at high plasma ethanol concentrations (greater than 100 mg/dl), women taking OCSs should not attempt to drink more than usual. PMID- 4042521 TI - Sulindac metabolism: the importance of an intact colon. AB - The pharmacokinetics of sulindac have been studied after a single 200 mg oral dose in six normal subjects and five patients with surgical ileostomies. The plasma concentration-time curves for sulindac were similar in both groups up to 12 hours after dosing, indicating similar absorption of the drug. Higher plasma concentrations of sulindac were found in normal subjects after 12 hours, but this late phase accounted for only 12% of the total AUC in the subjects. The sulfone metabolite showed a similar pattern, with no statistically significant difference in the total AUC, but in patients with ileostomy there was a halving of the AUC after 12 hours. Plasma concentrations of the active sulfide metabolite were similar in both groups up to 12 hours, but negligible concentrations were detected in the plasma of patients with ileostomy after 12 hours. Thus the AUC after 12 hours, which represented 55% of the total AUC in normal subjects, was reduced to only 7% in patients with ileostomy. The rate of reduction of sulindac in vitro by ileostomy effluent was only one hundredth that by normal feces. Our results suggest that the gut microflora are an important site of reduction of sulindac in man. Comparison of AUC values suggests that about half the total sulfide is formed by the gut bacteria, probably from sulindac excreted in the bile. PMID- 4042522 TI - A family study of genetic and environmental factors determining polymorphic hydroxylation of debrisoquin. AB - Debrisoquin hydroxylation capacity determined as the ratio of debrisoquin to 4-OH debrisoquin (DMR) in urine after a single oral dose (10 mg) was studied in 52 nuclear families comprising 226 subjects. The relative importance of genetic and environmental factors for DMR was studied by path analysis. There was a significant negative correlation between DMR and coffee intake but no significant correlations between DMR and sex, age, alcohol intake, or smoking habits. Path analysis showed that genetic heritability was 0.79 while cultural heritability was only 0.06. Complex segregation analysis gave evidence for a major locus with incomplete dominance (d = 0.28) between a recessive and an additive gene. The frequency of the major gene was 0.31, allowing an estimate of the frequency of slow hydroxylators in the Swedish population of 9.4%. There was also evidence for a multifactorial component accounting for 14% of the total variation. It was not possible to distinguish between the different genotypes within the rapid hydroxylator phenotype. Our data agree with previous studies in British and German populations showing that two alleles at a major autosomal locus can explain most of the observed variation in DMR. The frequency of slow hydroxylators in Sweden is very similar to that reported in other European studies. The debrisoquin metabolic phenotype seems to be extensively controlled by a monogenic system and not significantly influenced by environmental factors or age. PMID- 4042523 TI - Interethnic differences in genetic polymorphism of debrisoquin and mephenytoin hydroxylation between Japanese and Caucasian populations. AB - Interethnic differences in debrisoquin and mephenytoin hydroxylation have been compared between normal white (n = 183) and Japanese (n = 100) subjects with the 8-hour urinary metabolic ratio of debrisoquin and the urinary S/R enantiomeric ratio of mephenytoin to identify extensive (EM) and poor (PM) metabolizers. In white subjects the frequency of PMs was 8.7% and 2.7% for debrisoquin and mephenytoin, respectively. In contrast, in Japanese subjects no PMs of debrisoquin were identified, while the incidence of PMs of mephenytoin was 18%. These substantial differences (P less than 0.001) in polymorphic distributions of oxidative drug metabolizing ability have implications for interethnic efficacy and toxicity of drugs and other xenobiotics that are metabolized by the involved cytochrome P-450 isozymes. PMID- 4042524 TI - Stereoselective mephobarbital hydroxylation cosegregates with mephenytoin hydroxylation. AB - The 8-hour urinary recovery of 4-hydroxy-mephobarbital has been measured after oral administration of racemic mephobarbital (90 mg) in 17 extensive (EM) and six poor (PM) metabolizer phenotypes of mephenytoin. The recovery of this metabolite was measurable in every EM and ranged from 2.5% to 48% (10.9% +/- 1.9% of dose), but was not detected in any PM (less than 1% of dose). In EMs, the 8-hour urine recovery of 4-OH-mephobarbital after mephobarbital was approximately half that of 4-OH-mephenytoin over the same time after mephenytoin administration. One EM received similar doses of R- and S-mephobarbital on separate occasions. Urinary recovery of 4-OH-mephobarbital was 33% and less than 1%, respectively. These results suggest that mephobarbital is stereoselectively hydroxylated by the same drug metabolizing enzyme that is responsible for the stereoselective aromatic hydroxylation of mephenytoin. PMID- 4042525 TI - Effects of long-term therapy with naltrexone on body weight in obesity. AB - The endogenous opiate system is thought to be associated with the regulation of food intake and body weight. Opiate antagonists decrease food intake in animals, but there are no controlled studies in obese man to evaluate body weight response to naltrexone. Sixty obese people were randomized into three groups and given 0, 50, or 100 mg of the opiate antagonist naltrexone for 8 weeks in an outpatient, double-blind study. Weight loss was not significant in either the 50 or 100 mg groups as compared with placebo. However, when broken down by sex, women had a significant (P less than 0.05) weight loss of 1.7 kg, while men did not lose weight. Side effects were modest, but six subjects had one or more abnormal liver function test results; in one subject these abnormalities appeared to be clinically significant. The effects of naltrexone on weight loss were less than expected in light of prior animal studies, but further studies with a wider dose range of naltrexone may be indicated. PMID- 4042526 TI - Terazosin kinetics after oral and intravenous doses. AB - Terazosin kinetics were followed in normal subjects after intravenous doses of 0.5, 1.0, and 2.0 mg and oral doses of 1.0 mg. Plasma and urine samples were collected for the first 48 and 24 hours. The samples were analyzed by a sensitive HPLC assay developed in our laboratory. Mean calculated peak plasma levels from the 0.5, 1.0, and 2.0 mg intravenous doses were 25.0, 44.1, and 83.3 ng/ml. After a 1 mg oral dose the mean peak level was 19.6 ng/ml. Data were fit to a two compartment open model with mean elimination phase t1/2 values of 7.9, 8.9, and 10.1 hours for the ascending intravenous doses and 11.6 hours for the oral dose. Mean 0 to 24-hour urinary recovery after the intravenous doses was 14%, 13%, and 11%. It is concluded that terazosin kinetics are linear after oral and intravenous doses. PMID- 4042527 TI - Ventilatory effects of atenolol and bevantolol in asthma. AB - The cardioequipotency of 400 mg bevantolol and 100 mg atenolol was determined by measuring the exercise heart rate in healthy subjects. The beta-blockers were then used in these doses to investigate their ventilatory effects in patients with asthma. The effects of both drugs on forced expiratory flow parameters for large and small airways were assessed at rest and during and after exercise. A dose-response curve was then plotted after inhalation of the beta 2-adrenoceptor agonist terbutaline. Bevantolol significantly decreased the forced expiratory volume in 1 second (FEV1) and the peak expiratory flow rate (PEFR) at rest, while there was no such change with placebo or atenolol. Both beta-blockers decreased the maximal expiratory flow rates at 50% of forced vital capacity (MEF50) and after expiration of 75% of the forced vital capacity (MEF25) at rest; the decrease was larger after bevantolol than after atenolol. During atenolol there was a decrease in FEV1 and in PEFR (P less than 0.01) 15 minutes after exercise in comparison with preexercise values. There was no significant difference between pre- and postexercise values of MEF50 and MEF25 during atenolol dosing. After bevantolol there was only a small change in PEFR after exercise, probably because of the low preexercise values of the ventilatory indices with this drug. Inhalation of terbutaline up to a dose of 2 mg significantly improved all ventilatory indices measured, but with bevantolol the values after 2 mg inhaled terbutaline were lower than the initial values.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4042528 TI - Transdermal nicotine reduces cigarette craving and nicotine preference. AB - The effects of transdermal nicotine in 10 cigarette smokers were studied in a within-subjects, double-blind design. Either 8 mg nicotine base in a 30% aqueous solution or an inactive placebo solution was applied to intact skin under a polyethylene patch. Subjective reports of cigarette craving were collected every 30 minutes during a 90-minute smoking abstinence period. Immediately before and after this abstinence period subjects smoked through a smoke mixing device that allowed them to select their desired nicotine intake with each puff. Transdermal nicotine significantly increased saliva nicotine levels within 30 minutes after application. Cigarette craving was significantly lower in the nicotine condition than in the placebo condition. Nicotine preference during the initial puffs of the smoke mixer test at the end of 90 minutes of deprivation was also decreased by transdermal nicotine. In contrast, measures of cumulative smoke intake were not affected by the nicotine dose used. Our results suggest that transdermal nicotine may enhance success in smoking cessation by preventing the rise in cigarette craving usually observed after cessation. Transdermal nicotine may be preferable to other routes of nicotine administration because of the relative absence of adverse side effects. PMID- 4042529 TI - Pharmacokinetics of high-dose pentobarbital in severe head trauma. AB - High-dose pentobarbital infusion has been advocated as an effective adjunct in controlling persistent intracranial hypertension after severe head trauma in patients refractory to conventional therapy. Pentobarbital disposition was assessed in 10 adults with severe nonpenetrating head injury after an intravenous loading dose of sodium pentobarbital, 10 mg/kg, infused over 1 hour, followed by a continuous infusion at 0.5 to 3.0 mg/kg/hr provided the cerebral perfusion pressure remained greater than 50 torr. Pharmacokinetic parameters of volume of distribution at steady state (Vss), total body clearance (CL), and t1/2 for the patients with trauma were statistically compared with similar estimates reported for seven adult subjects without head injury. On discontinuation of the pentobarbital infusion, serum concentrations in the patients followed a monoexponential decline with a mean (+/- SD) t1/2 and Vss that were significantly less than values reported for the control subjects (15.6 +/- 3.9 vs. 22.3 +/- 4.0 hours and 44.0 +/- 11.7 vs. 63.4 +/- 15.2 L, respectively). However, there was no significant difference between the mean pentobarbital CL of the patients (2.0 +/- 0.7 L/hr) and the subjects (2.0 +/- 0.4 L/hr). To our knowledge this is the first report on the disposition, elimination, and intrasubject variability of high-dose pentobarbital infusion in adult patients with head trauma. PMID- 4042530 TI - New insights into the pharmacokinetics of spironolactone. AB - Four healthy men took a single oral dose of 200 mg spironolactone after a standardized breakfast. Blood samples were drawn until 24 hours after dosing. A specific HPLC method was used to determine the serum concentrations of spironolactone and its metabolites 7 alpha-thiomethylspirolactone, 6 beta-hydroxy 7 alpha-thiomethylspirolactone, and canrenone. Pharmacokinetic parameters were derived from the serum concentration-time course of each compound. Spironolactone, 7 alpha-thiomethylspirolactone, and canrenone are known to have antimineralocorticoid activity in man. Our study demonstrated that: (1) 7 alpha Thiomethylspirolactone is the main metabolite of spironolactone after a single oral dose as judged by the AUC(0-24) and the maximum concentration; and (2) unchanged spironolactone was detected in serum, with a maximum concentration at 1 hour and detectable levels up to 8 hours after dosing. Our findings are contrary to the widely accepted belief that spironolactone is metabolized too rapidly to be detected in serum after oral dosing and that canrenone is the principal metabolite of spironolactone. PMID- 4042531 TI - Concomitant food intake does enhance the bioavailability and effect of hydralazine. PMID- 4042532 TI - Assessment of tissue sensitivity to insulin in uraemic patients on long-term haemodialysis therapy. AB - Glucose intolerance is a common concomitant of untreated chronic renal failure, but the effect of long-term treatment on the insulin resistance believed to be behind it is as yet not clarified. Peripheral tissue sensitivity to insulin was therefore examined in 7 dialyzed uraemic patients, 8 undialyzed uraemic and 8 matched healthy subjects using the hyperinsulinaemic euglycaemic clamp technique. The dialyzed subjects had been on maintenance haemodialysis for a mean of 4 yr (range, 3-131 months) and were studied both before and after a single random dialysis. The clamping was performed during 150 min using a glucose controlled insulin infusion system (Biostator). Insulin was infused at a rate of 2.0 mU/kg/min. Tissue sensitivity to insulin was expressed as glucose uptake (M) at steady state (90-150 min) over steady state serum insulin concentration (I). While M was significantly greater in healthy subjects (12.52 +/- 1.02 mg/kg/min, mean +/- 1 SEM) than in dialyzed uraemics (9.59 +/- 0.78 mg/kg/min and 9.36 +/- 0.70 mg/kg/min, both p less than 0.05), M/I was similar in chronically dialyzed patients (before and after dialysis: 0.098 +/- 0.017 mg/kg/min per microU/ml vs 0.104 +/- 0.020 mg/kg/min per microU/ml) and in controls (0.111 +/- 0.015 mg/kg/min per microU/ml; p greater than 0.20). In contrast M/I ratio of uraemic subjects who had never been dialyzed (0.062 +/- mg/kg/min per microU/ml) was significantly reduced (both p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4042534 TI - Restricted effector cell function in ADCC. AB - Human effector cell function in ADCC reactions was studied as a result of observations showing discrepant ADCC reactivities among different effector cell populations. Effector cells prepared from ten blood donors were tested individually and as a pool against a battery of nine antisera-target cell combinations in an 11-x-9 matrix. The results identified individuals with weak, intermediate, and strong effector cell functions; however, there was a wide range of ADCC reactivity by each person's effector cells against the nine targets. No single antibody-target cell combination was consistently subjected to the least kill or greatest kill by the different effector cell preparations. Pooled effector cell responses were found to be weaker than expected. There was no relationship of age or sex with effector cell function, but a trend was noted for strong and weak reactions to be associated with HLA-DR7 and DR1, respectively. Neither the sharing of HLA antigens between effector and target cells nor self ADCC reactivity could account for the variations in effector cell function. Exploratory principal components factor analysis suggested that recognition of antibody-target cell combinations by effector cells was represented by three major groupings. These data collectively indicate the existence of an allorestrictive Fc receptor recognition step in ADCC responses. PMID- 4042533 TI - Effect of psychosocial factors on success in a program of self-glucose monitoring. AB - We examined prospectively the relationship of psychosocial factors to glycemic control in a program of self-glucose monitoring (SGM). Measured intelligence (IQ), educational level, and socioeconomic status (assessed by the Two-Factor Index of Social Position) were determined in 25 patients who were followed during 6 months of self-glucose monitoring. Personality categories, reflecting degrees of psychological disturbance, were assigned using the Minnesota Multiphasic Personality Inventory (MMPI). None of the measured psychosocial variables correlated significantly with initial Hgb A1 values. In contrast, after 6 months of SGM, Hgb A1 levels correlated significantly with both socioeconomic status (r = 0.42, p less than 0.05) and educational levels (r = -0.42, p less than 0.05). Hemoglobin A1 levels also correlated significantly with the recorded frequency of SGM (r = -0.65, p less than 0.01), a measure of patient compliance. No significant correlation between IQ and Hgb A1 levels was seen, either initially or during follow-up. High A1 values differed significantly among groups classified by MMPI testing. Patients with severe psychological abnormalities had higher (p less than 0.05) mean Hgb A1 levels. We conclude that psychosocial factors, but not measured intelligence, have an important bearing on patient success in a program of SGM. PMID- 4042535 TI - Magnetic albumin/protein A immunomicrospheres. II. Specificity, reproducibility, and resolution of the magnetic cell separation technique. AB - Magnetically responsive albumin/protein A immunomicrospheres (MIMS) were prepared by reacting a mixture of albumin, iron oxide, and protein A in a two-phase emulsion coagulation procedure. The protein A ligand permits strong affinity binding of the monoclonal anti-HLA BW6 antibody to the 500-nm MIMS in a one-step process. HLA BW6+ and BW4+ human peripheral blood lymphocytes and mixtures of both were incubated with these MIMS. The findings obtained after only one run in a magnetic field were as follows: depletion of 98.6 +/- 0.9% of the target cells when 2 mg MIMS/10(6) cells were used, unspecific trapping of 5.9 +/- 2.5% of the nontarget cells from cell mixtures, and effective separation of cell populations as small as 1-0.1%. Thus, using albumin/protein A MIMS, the magnetic cell separation technique is simple, rapid, and highly sensitive. PMID- 4042536 TI - Antigen-specific immunostimulation of amino acid transport: proposed method for the diagnosis of tuberculosis in cattle. AB - Preliminary data on a novel method for the diagnosis of bovine tuberculosis (TB) has been presented. This method is based on increased amino acid transport in specifically stimulated lymphocyte cultures. Lymphocytes isolated from TB infected or -sensitized cattle and cultured with the TB antigen PPD-B had noticeably enhanced amino acid transport after 1-3 days. Transport continued to increase for up to 5 days of culture with the antigen. PPD-B did not stimulate transport in lymphocytes from nonsensitized animals. The new method correlated well with the tuberculin skin test and antigen-induced lymphocyte proliferation measured by flow cytometry. PMID- 4042537 TI - Presidential address. Responding to the challenge. PMID- 4042538 TI - Platelet associated IgG--an overview. PMID- 4042539 TI - Informed consent for research publication of patient-related data. PMID- 4042540 TI - Validation of a Doppler technique for beat-to-beat measurement of cardiac output. AB - We have measured aortic flow in the ascending aorta in man with a Bach-Simpson BVM 202 blood velocity meter, and aortic root diameter by M-mode echocardiography, and thus derived beat-to-beat cardiac output (Q). We tested the technique in 21 patients (53 comparisons) with various cardiovascular problems against a thermodilution method, and in four normal subjects at rest and two levels of exercise (50 and 100 W) against a nitrous oxide rebreathing method. We obtained excellent overall correlation in a range of 0.5-10 litres/min (r = 0.98, n = 77, sy,x = 0.48 litre/min), the formula for the least squares regression being: (Q Doppler) = 0.95 (Q Thermodilution/N2O) + 0.11 litre/min. The Doppler signal is sufficiently noise-free to obtain maximum acceleration of flow from the first derivative of velocity. PMID- 4042541 TI - A circadian rhythm of proteinuria in patients with a nephrotic syndrome. AB - Circadian variations in proteinuria were studied in 17 patients with different types of glomerulopathies. During 3-4 successive days urine was collected over periods of 3 h under standardized conditions. Thirteen of the 17 patients showed a circadian rhythm of their proteinuria with a maximum excretion in daytime around 16.00 hours and a minimum excretion at night around 03.00 hours. In the majority of patients the urinary excretory rhythms of albumin, transferrin and immunoglobulin G were 'in phase' with each other and with the circadian rhythm of total protein excretion. Nine patients had a larger degree of rhythmicity for immunoglobulin G than for transferrin excretion. In eight of them a circadian rhythm of the selectivity index of proteinuria was seen with the lowest index at night. No relation was observed between the circadian rhythm of proteinuria and the type of glomerulopathy. PMID- 4042542 TI - Serum immunoreactive erythropoietin in hypoxic lung disease with and without polycythaemia. AB - We studied 20 patients with chronic airflow obstruction, 10 patients without polycythaemia and 10 patients with compensatory polycythaemia having respectively mean red cell mass 24.7 (SD 4.2) and 47.8 (SD 7.5) ml/kg, mean daytime PaO2 7.6 and 6.9 kPa, mean FEV1 0.85 and 0.821. Groups were matched for severity of daytime arterial hypoxaemia but nocturnal arterial oxygen desaturation was more severe in the patients with polycythaemia than in those without. We also studied six additional patients with chronic airflow obstruction and polycythaemia and 19 normal controls. Estimates of serum immunoreactive erythropoietin (siEp) in those without polycythaemia were 19 m-i.u./ml (geometric mean) with 95% confidence range 11-35 m-i.u./ml and stable during 3 months. In those with polycythaemia they were similar and consistent in five and, in the other five, higher on at least one occasion. There was no significant difference between siEp in daytime (12.00 hours to 16.00 hours) and morning (07.00 hours) samples but geometric mean estimates of erythropoietin in paired daytime and morning samples were higher and more variable in patients with polycythaemia than in those without. The geometric mean estimate of siEp in all patients with chronic airflow obstruction and polycythaemia was greater than in normal subjects but, despite secondary polycythaemia, siEp could be in the range for normal subjects. In the patients with polycythaemia we were unable to predict the finding of normal or elevated siEp. Changes in siEp after erythrapheresis (10-26% reduction in packed cell volume) were observed in the 10 patients with polycythaemia and in one without. One month after erythrapheresis, packed cell volume remained below and siEp was above initial pretreatment levels, implying an erythropoietin secretory response and that the development of secondary polycythaemia had induced a fall in siEp. PMID- 4042543 TI - Changes in plasma free 3,4-dihydroxyphenylethylene glycol and noradrenaline levels after acute alcohol administration. AB - The effects of alcohol (0.9 g/kg) compared with placebo (400 ml of orange juice) on plasma noradrenaline and 3,4-dihydroxyphenylethylene glycol levels, and on erect and supine blood pressures and heart rates, were studied in eight normal male volunteers. Alcohol caused a rise in noradrenaline levels that commenced approximately 30 min after drinking and lasted about 4 h. In contrast, 3,4 dihydroxyphenylethylene glycol levels fell immediately after alcohol administration and remained low for at least 6 h. Acute alcohol administration alters noradrenaline catabolism, and may have a dual effect of increasing noradrenaline release and decreasing noradrenaline clearance. Alcohol caused a transient rise in erect and supine blood pressures that preceded the rise in plasma noradrenaline. Thereafter erect blood pressures fell compared with control. This fall was associated with a progressive rise in both supine and erect rates, and reached a maximum several hours after the maximum levels of blood alcohol. The major effect of acute alcohol administration is to lower blood pressure and induce a reflex tachycardia. Changes in noradrenaline and 3,4 dihydroxyphenylethylene glycol levels did not readily explain changes in blood pressure or heart rate, suggesting that alcohol induced changes in noradrenaline metabolism occur largely independent of changes in blood pressure and heart rate. PMID- 4042544 TI - A technique for the measurement of orthophosphate in human erythrocytes, and some studies of its determinants. AB - A technique is described for the determination of orthophosphate (Pi) in human erythrocytes. The advantages of the technique are that it uses whole blood rather than separated erythrocytes, that it avoids major hydrolysis of organic phosphates, that it takes account of incomplete recovery of Pi and that it minimizes the effects of chilling the cells. In chilled samples from 46 patients in an intensive care unit, the cellular concentration of Pi was proportional to that in plasma. Blood samples from nine normal subjects were incubated at 37 degrees C. The cellular Pi was 0.79 mmol/litre of cells using an external standardization and 0.67 using an internal standardization. When the same cell samples were chilled on ice for 30 min, the internally standardized value decreased further to 0.57 mmol/litre of cells. These results suggest that differences in recovery, and the extent of chilling, contribute to the variability in the previously reported values for erythrocyte Pi. If Pi, like chloride, had distributed passively between cells and plasma in these samples, the cell to plasma molar concentration ratio for Pi should have been 0.29, compared with the measured value of 0.64. This difference suggests that some factor, in addition to passive diffusion, determined the distribution of Pi. PMID- 4042545 TI - Phosphate metabolism in erythrocytes of critically ill patients. AB - Orthophosphate (Pi), adenosine 5'-diphosphate (ADP), adenosine 5'-triphosphate (ATP) and 2,3-diphosphoglycerate (2,3-DPG) were measured in the erythrocytes of patients in an intensive care unit. The patients' plasma concentration of Pi varied from 0.1 to 4.2 mmol/l, and the corresponding concentration in erythrocytes varied from 0.1 to 2.0 mmol/litre of cells. Marked ATP depletion (less than 1 mmol/litre of cells) was only observed when erythrocyte Pi was less than 0.3 mmol/litre of cells and plasma Pi was less than 0.35 mmol/l. No dependence of 2,3-DPG concentration on the cellular concentration of Pi was detected. The phosphorylation potential [ATP]/([ADP] X [Pi]) varied inversely with the erythrocyte concentration of Pi. Hence the calculated free energy of hydrolysis of ATP in the cell increased from -58 kJ/mol in the most hypophosphataemic samples to -51 kJ/mol in the most hyperphosphataemic. Such changes may adversely affect cell function by altering the steady state mass action ratios of ATPase reactions. When erythrocytes from normal donors were incubated in solutions containing 1 or 5 mmol/l Pi, the cellular concentrations of Pi stabilized at 1.09 and 2.85 mmol/litre of cells respectively. The corresponding rates of lactate production were 2.09 and 3.11 mmol h-1 litre-1 of cells. In spite of this stimulation of glycolysis (and hence of the flux through ATP synthesizing steps of the Embden-Meyerhof pathway), no significant change in ATP concentration was observed. As in the patients' cells, this indicates that, when extracellular Pi concentrations are perturbed, the concentrations, in erythrocytes, of organic phosphates are more closely regulated than the concentration of Pi. PMID- 4042546 TI - Twenty-four hour hormonal and metabolic profiles in uraemic patients before and during treatment with continuous ambulatory peritoneal dialysis. AB - Circulating intermediary metabolite and hormone concentrations were measured at intervals over 24 h in five uraemic patients before starting dialysis and after 3 months' treatment with continuous ambulatory peritoneal dialysis (CAPD) and in 13 non-uraemic normal controls. Fasting and postprandial glucose concentrations were significantly raised in uraemic patients undialysed and on CAPD but 24 h mean (+/ SEM) levels fell from 6.63 +/- 0.40 to 6.00 +/- 0.26 mmol/l (P less than 0.02) after 3 months' dialysis despite peritoneal glucose absorption. Insulin levels were raised in uraemic patients but were unchanged by CAPD. Uraemia was associated with raised levels of the gluconeogenic precursors lactate and alanine and a further rise in fasting and 24 h mean alanine concentrations occurred with CAPD. Fasting total ketone body concentrations were raised in undialysed uraemic patients but concentrations were suppressed throughout the 24 h in CAPD subjects. Fasting triglyceride concentrations were increased in uraemic subjects and mean 24 h levels rose by 30% from 1.55 +/- 0.42 mmol/l before dialysis to 2.02 +/- 0.59 mmol/l during CAPD. Non-esterified fatty acid concentrations were low in uraemic patients and remained low during CAPD. Undialysed and dialysed uraemic patients displayed raised plasma glucagon concentrations throughout the 24 h, suppression of the normal nocturnal secretion of growth hormone and raised mean cortisol levels, which were 23% (CAPD) to 57% (undialysed) higher than in normal controls. The endocrine and metabolic abnormalities of uraemia are not fully corrected by CAPD. Many of the additional changes observed during CAPD reflect an adaptation to the constant absorption of peritoneal glucose. PMID- 4042547 TI - Effects of age on body temperature and blood pressure in cold environments. AB - Mean deep body temperature fell by 0.4 +/- 0.1 (SD) degrees C in five sedentary, clothed 63-70 year old men and by 0.1 +/- 0.1 degrees C in four young adults after 2 h exposure in still air at 6 degrees C (P less than 0.001). The mean increase in systolic and diastolic pressure was significantly greater (P less than 0.002) in the older subjects (24 +/- 4 mmHg systolic, 13 +/- 4 mmHg diastolic) than in the young (14 +/- 6 mmHg systolic, 7 +/- 3 mmHg diastolic) after 2 h at 6 degrees C. A small rise in blood pressure occurred in the older men at 12 degrees C, but there was no increase in either group at 15 degrees C. The association of variables is particularly marked between systolic blood pressure and core temperature changes at 6 degrees C. There were no appreciable cold-adaptive changes in blood pressure or thermoregulatory responses after 7-10 days repeated exposure to 6 degrees C for 4 h each day. Blood pressure elevation in the cold was slower but more marked in the older men. These changes in blood pressure may provide a possible basis for delineating low domestic limiting temperature conditions. PMID- 4042548 TI - Abnormal vascular function and morphology in pre-eclampsia: a study of isolated resistance vessels. AB - In order to obtain direct information about vascular changes associated with pre eclampsia, the morphological and functional characteristics of isolated omental resistance vessels from 11 women with pre-eclampsia, 10 normotensive pregnant women and eight normotensive non-pregnant women were determined. In vessels from the women with pre-eclampsia, the ratio of media thickness to lumen diameter was increased, compared with that in vessels from the other two groups. The vessels from the women with pre-eclampsia had an increased responsiveness to angiotensin II and a decreased rate of relaxation, but only when compared with the vessels from the normotensive pregnant women. However, no difference in responsiveness to noradrenaline was found between any of the groups. The angiotensin II responsiveness of the vessels from the women with pre-eclampsia and from the non pregnant women were similar, suggesting that pre-eclampsia is associated with an absence of the change in vascular function which normally occurs during pregnancy. The study provides direct evidence for an involvement of vascular abnormalities in the pathogenesis of pre-eclampsia. PMID- 4042549 TI - Beta-adrenoceptor responsiveness and plasma catecholamines as determinants of cardiovascular reactivity to mental stress. AB - Twenty-five normotensive men were subjected to two periods of mental stress involving a cognitive task and a competitive electronic game. Plasma catecholamines, heart rate and blood pressure were measured before and during mental stress. Responsiveness to beta-adrenoceptor stimulation was also determined in each subject by measurement of heart rate responses to bolus injections of isoprenaline. Both periods of mental stress were associated with significant increases in systolic and diastolic blood pressures, heart rate and plasma adrenaline, but not plasma noradrenaline. Heart rate responses to mental stress varied widely, with increases ranging from 1 to 48 (mean +/- SD 13.5 +/- 10.6) beats/min for the cognitive task and from 2 to 49 (20.4 +/- 14.0) beats/min for the electronic game. Systolic blood pressure responses also varied widely and showed significant positive correlations with heart rate responses. Significant relationships were found between heart rate responses to both forms of mental stress and cardiac sensitivity to isoprenaline, subjects with low responsiveness to beta-adrenoceptor stimulation tending to have smaller heart rate responses to mental stress than subjects with high responsiveness to beta-adrenoceptor stimulation. Relationships were also found between plasma adrenaline responses and heart rate responses to mental stress, although these did not reach significance. Considerably improved relationships were found when heart rate responses were correlated with a single variable generated from the product of the adrenaline response and the inverse of the dose of isoprenaline required to raise heart rate by 25 beats/min. It is concluded that wide variation is shown between different individuals in responsiveness to beta-adrenoceptor stimulation and that this is an important factor in the variability between individuals in heart rate and systolic blood pressure responses to mental stress. Both catecholamines and adrenoceptor-mediated responses to catecholamines should be examined when determining the physiological basis for differences in cardiovascular reactivity to mental stress between individuals or groups. PMID- 4042550 TI - A new approach to non-invasive quantitative study of hepatic haemodynamics using radiocolloids in vivo. AB - A non-invasive radioisotopic method for the study of liver haemodynamics is described. Data collected by means of a computerised gamma camera for about 4 min after intravenous administration of 99Tcm human serum albumin colloids were analysed using a new mathematical model formulated on a physiopathological basis. Several quantities of possible clinical interest were determined, namely parameters related to liver blood flows, intrahepatic shunts, the intrahepatic space of distribution of the tracer, transit times and extraction efficiency. Results are not affected, within certain limits, by the shape of the radioactive bolus and, with the exception of extraction efficiency, they appear to be independent of the size of the radiocolloidal particle. The dose employed (3-4 mCi) is comparable with that used in liver scintigraphy. Results in 19 subjects with normal liver function, 45 patients with liver cirrhosis and 7 patients with focal liver lesions were in good agreement, from a quantitative viewpoint, with known physiopathological data, thus validating this method in comparison with other more traumatic and/or less practical techniques, which provide less complete information on liver haemodynamics. The method proposed appears to be sufficiently accurate, reproducible, safe and practical, and may thus be considered suitable for routine use in the assessment of functional aspects of liver perfusion for clinical purposes. PMID- 4042552 TI - A new laser interferometer for the stimulation of pattern-reversal visual evoked potentials. AB - A laser interferometer for visual-evoked-potential (VEP) stimulation that allows a rapid pattern reversal in less than 0.5 ms and a continuous variation of the spatial frequency of the pattern is described. The interferometer is applied for the assessment of objective visual acuity. The Fourier transform of the VEP response to the rapid pattern reversal shows an extremely small bandwidth. PMID- 4042551 TI - Effects of changes in heart rate and atrial filling pressure on the performance characteristics of isolated perfused pumping rat hearts. AB - Biomechanical indices of left ventricular performance were measured and computed by an on-line minicomputer in 13 isolated perfused working rat hearts subjected to a regimen of left atrial filling pressures and heart rates, to determine perfusion conditions for optimum heart work. We found that maximum values of most of the indices are achieved at a left atrial filling pressure of 20 to 25 cm H2O and a heart rate of 330 to 360 beats/min. Most of the performance indices when considered as functions of left atrial filling pressure display Starling-type behaviour: they rise with increasing left atrial pressure, reach a maximum at 20 to 25 cm H2O, and decline with further increases in left atrial pressure. Values for left ventricular (dP/dt)max, between 6000 to 8000 mm Hg s-1, and -(dP/dt)min, between 4000 to 6000 mm Hg s-1, are considerably higher than values previously reported. We believe this to be due to improved sampling techniques. PMID- 4042553 TI - Calibration and measurement of the inhaled smoke volume in cigarette smoking. PMID- 4042554 TI - A sound stimulator with electronic memory for testing infants' hearing. PMID- 4042555 TI - The claimed vasodilatory effect of a commercial permanent magnet foil: results of a double-blind trial. PMID- 4042556 TI - Comment on "Photon scattering measurements of calcaneal bone density: results of in vivo longitudinal studies'. PMID- 4042557 TI - Oral acyclovir pharmacokinetics. PMID- 4042558 TI - Change in enzyme content and manufacturer of Viokase. PMID- 4042559 TI - Gastrointestinal transit times of cathartics used with activated charcoal. PMID- 4042560 TI - Theophylline pharmacokinetics in paraplegic subjects. PMID- 4042561 TI - Reservoir aerosol delivery systems. PMID- 4042562 TI - Metallic taste associated with tetracycline therapy. PMID- 4042563 TI - Primary acquired sideroblastic anaemia and myeloproliferative disease: a report on three cases. AB - Three patients who presented with primary acquired sideroblastic anaemia (PASA) later developed myelofibrosis (MF). As both are clonal disorders a second mutation is suggested. PMID- 4042564 TI - Fresh frozen plasma in the treatment of chronic autoimmune thrombocytopenic purpura in adults: evidence for potentiating effect of vincristine. AB - Five adult patients with chronic autoimmune thrombocytopenic purpura (ATP) were given fresh frozen plasma infusion (FFP) as an alternative to intravenous gamma globulin (IV Ig). The effect of vincristine (VCR) and other agents given concomitantly is discussed and a synergistic phenomenon between VCR and FFP is proposed. This approach may provide a rational and economical alternative to the use of IV Ig in the treatment of chronic ATP in adults and it is hoped that a prospective trial can be initiated. PMID- 4042565 TI - Quality of oral anticoagulant therapy. AB - Three hundred and eighty-four patients were studied for up to 1 year while on continuous oral anticoagulant therapy and the quality of control of therapy was assessed. Two hundred and thirty-five patients were on continuous therapy throughout the year (long-term group), 73 were treated for a period between 3 and 12 months (intermediate group) and 76 were treated for less than 3 months (short term group). The therapeutic objective was to achieve and maintain British Ratio (BR) between 2.0 and 4.0. Nineteen percent of the results in the long-term group, 26.6% in the intermediate group and 41.1% in the short-term group fell outside this range. Among the long-term group only 25.1% and in the intermediate group 12.3% had all their results within the control range. It is concluded that the quality of therapeutic control of oral anticoagulant therapy needs to be improved. PMID- 4042566 TI - In-vivo neutrophil migration and nitroblue tetrazolium reduction in sickle cell disease. AB - In order to determine the contribution of neutrophil malfunction to the phenomenon of enhanced susceptibility of sickle cell disease patients to bacterial infection, the in-vivo neutrophil migration capacity in 23 sickle cell patients and in 14 normal controls; and the neutrophil reduction of nitroblue tetrazolium dye in 74 sickle cell patients and in 78 normal controls were studied. Secondarily the usefulness of the NBT test in distinguishing between osteomyelitis and uncomplicated bone pain was examined. No impairment of neutrophil migratory capacity was evident as no significant difference was observed between the mean migrated neutrophil count in the sickle cell subjects (1.99 X 10(9)/1) and that in normal controls (2.08 X 10(9)/1). The mean NBT scores were 19.9 +/- 8.9% in non-infected controls and 41.3 +/- 14.6% in infected controls (P less than 0.001). In sickle cell disease they were 23.6 +/- 6% in steady state subjects, 29.2 +/- 16.4% in sterile painful crises, 42.9 +/- 15% in non-osteomyelitic bacterial infection (P less than 0.001) and 18.9 +/- 4.2% during osteomyelitis. Thus all sickle cell subjects apart from those with osteomyelitis showed significant increases in the NBT scores during bacterial infection. The low score in sickle cell osteomyelitis is possibly associated with a relative neutrophil phagocytic defect which requires further elucidation. The NBT test was not useful in distinguishing uncomplicated painful crisis from early osteomyelitis in sickle cell disease. PMID- 4042567 TI - An assessment of the Ortho ELT-800 WBC and three-part WBC screen. AB - The ELT-800 WBC and three-part WBC screen have been evaluated. Technical assessment showed each to be satisfactory but in a small number of samples, the total WBC was found to be incorrect. Discrepancies were found in some cases of chronic lymphatic leukaemia, sickle cell disease and paraproteinaemia. The reasons for these differences are discussed. In the population studied, an accurate WBC screen was obtained on 87.3% of samples. Initial instrument WBC screen rejection occurred on 12.7% but in only 2.1% could no explanation be found to account for this. PMID- 4042568 TI - An evaluation of the Sequoia-Turner Cell Dyn 900. AB - A formal evaluation of the Sequoia-Turner Cell Dyn 900, a compact eight-parameter semi-automated blood cell counter, was carried out in a small paediatric haematology laboratory. The instrument's precision, linearity and carry-over were adequate. Comparison with a Coulter ZF6 system plus visual platelet count showed good agreement, and results in the UK National External Quality Assessment Scheme also compared well with 'all methods' values. Throughput was assessed at 54 eight parameter counts per hour. The machine proved to be reasonably economical, highly reliable and easy to operate. It was popular with staff and can be recommended, particularly for the smaller laboratory. PMID- 4042569 TI - A rapid technique for the estimation of fibrinogen. PMID- 4042570 TI - Use of danazol in the hereditary coagulation disorder hypofibrinogenaemia. PMID- 4042571 TI - Hypersensitivity to folic acid therapy. PMID- 4042572 TI - Ammonia metabolism during exercise in man. AB - Physical exercise is accompanied by increased plasma levels of ammonia but it is not known whether this rise primarily reflects accelerated formation in muscle or decreased removal by the liver. Consequently, leg and splanchnic exchange of ammonia was examined, using the catheter technique, in 11 healthy subjects at rest, during three consecutive 15 min periods of bicycle exercise at gradually increasing work loads (35%, 55% and 80% of maximum oxygen uptake) and for 60 min during post-exercise recovery. The basal arterial ammonia level was 22 +/- 2 mumol/l, the concentration rose curvilinearly in response to increasing work loads (peak value 84 +/- 12 mumol/l), and fell rapidly after exercise, reaching basal levels after 30-60 min. A linear regression was found for ammonia levels in relation to lactate concentrations at rest and during exercise (r = 0.85, P less than 0.001). A significant relationship was also observed between arterial ammonia and alanine levels (r = 0.75, P less than 0.001). Leg tissues showed a net uptake of ammonia in the basal state (2.4 +/- 0.5 mumol/min). During exercise this changed to a net production, which increased curvilinearly with rising work intensity (peak value 46 +/- 15 mumol/min) but reverted to a net ammonia uptake at 30-60 min after exercise. Splanchnic ammonia uptake (basal 12 +/- 2 mumol/min) did not change in response to exercise but increased transiently during the early post-exercise period. From the above observations we conclude that the hyperammonaemia of exercise comes primarily from muscle release, while the splanchnic removal of ammonia is essentially unaltered. Part of the ammonia formed in contracting muscle is most likely used in the synthesis of amino acids, mainly glutamine and probably alanine. PMID- 4042573 TI - A simplified technique for measurements of energy expenditure and substrate oxidation in man. AB - A technique is described for simultaneous measurements of energy expenditure and oxidation of exogenous substrates in man. The equipment comprised a semi-opened respiratory hood operated by a negative-flow pressure of the gas flow through the system. The system was constructed by assembling commercially available components with high analytical precision into an integrated constellation. We present results of instrument accuracy, assessed by calibration, and the coefficient of variation (CV) for calibration procedures of the total system, as well as findings with regard to the degree of reproducibility of applied investigations on both healthy volunteers and hospitalized patients. The overall coefficient of variation was 3-4% of the mean values for RQ and energy expenditure. This includes both biological and methodological variation. The cost of this system is less than that for a commercially available system with a similar performance. PMID- 4042575 TI - Reproducibility of coronary haemodynamics and cardiac metabolism during pacing induced angina pectoris. AB - The reproducibility of coronary sinus blood flow (CSBF) (thermodilution technique) and myocardial metabolism (exchange of oxygen, lactate, free fatty acids, glucose, citrate, glutamate and alanine) during two identical pacing periods separated by 45 min were studied in eight patients with chronic coronary artery disease. The mean of the individual difference (delta-values) between values during the first (T1) and second (T2) test, at corresponding times (rest, pacing and after 3-5 min of recovery), were calculated and expressed as a percentage of the resting level of each parameter in order to assess their reproducibility. All patients experienced angina pectoris during both pacing sessions, and pacetime to onset of symptoms did not differ between the tests. Group values for haemodynamics and exchange of metabolites were acceptably reproducible throughout the period under study. Mean delta-values of CSBF ranged from 10% to 16% and myocardial oxygen uptake from 14% to 22% in relation to the resting levels. In contrast, mean delta-values of metabolites ranged from 5% to 136% in relation to the respective A-V differences during the study. The greatest variation occurred during pacing and of all the metabolites lactate exchange varied most. A spontaneous variation in the degree of ischaemia during repeat stress tests might be the major reason for the metabolite variability. Changes in CSBF, however, tended to correlate inversely to the delta-aortocoronary sinus differences of substrates during pacing. Precision of chemical analysis and blood sampling technique were of minor importance for the variability. Since lactate exchange varied most, the study suggests that additional measurements should be made of more metabolites when assessing the efficacy of therapy by means of myocardial metabolism. PMID- 4042574 TI - Autonomic cardiovascular responses in old age. AB - The effect of age on autonomically mediated cardiovascular responses to certain manoeuvres was studied in 15, healthy, old men and women (60-80 years). The results were compared with groups of healthy young (about 25 years) and middle aged (about 45 years) subjects. There was no significant reduction in cardiovascular responses between the young and middle-aged groups. Respiratory sinus arrhythmia, and heart rate, blood-pressure and contralateral forearm blood flow increases to isometric hand grip, as well as the heart rate decrease during a dive reflex test, were significantly attenuated in the old age group. The Valsalva ratio, and the heart rate and blood-pressure changes during an 8 min orthostatic test did not differ between the old and the two younger age groups. There seems to be only a moderate attenuation of autonomic cardiovascular responses to about 60 years, after which there is a more rapid decline. The difference in reduction between different responses, even those mediated by the same type of autonomic nerve, suggests that the decreased responses are not due to an isolated impaired function of the peripheral autonomic nerve. The impairment may be due to the receptor organ or a combination of defects in function of several parts of the autonomic nervous system in old age. PMID- 4042576 TI - An evaluation of finger systolic-pressure response to local cooling in the diagnosis of primary Raynaud's phenomenon. AB - Finger systolic-pressure (FSP) in response to local cooling has been evaluated as a diagnostic test in 28 females with primary Raynaud's phenomenon (PRP). The mean FSP (%) at 15 degrees C and 10 degrees C was significantly lower in the patients than in 28 age- and sex-matched controls but there was a large overlap in the individual responses. Diagnostic sensitivity of FSP (%) at 10 degrees C was only 57%. Increasing the sensitivity of the test lowered the specificity as the number of false positives rose. This also reduced the predictive value for a positive test. As a diagnostic test of PRP in individuals, the measurement of FSP appears to be of limited value, except in severe cases when complete vessel closure often occurs. Measurement of FSP will classify groups correctly and this objective physiological measure of Raynaud's phenomenon may have a place in group comparisons. PMID- 4042577 TI - The influence of transducer position on the M-mode echocardiographic measurement of the left atrial dimension. AB - Eighty-five subjects were investigated to see if the left atrial dimension (LAD) determined by M-mode echocardiography varies with different placements of the transducer in the parasternal long-axis view. Satisfactory images from the third and fourth intercostal spaces were obtained in all subjects. A satisfactory image from the second, third and fourth intercostal spaces was obtained in 58 subjects and from the third, fourth and fifth intercostal spaces in 27 subjects. The mean LAD was significantly smaller (P less than 0.001) in the fourth intercostal space than in the third. The mean value obtained from the fifth intercostal space was smaller than that from the fourth. The beam pathway seen on the two-dimensional echocardiogram indicates that the transducer should preferably be placed in the third intercostal space. If the transducer is placed in a lower intercostal space the measured left atrial dimension might be underestimated. PMID- 4042579 TI - [Cardioinhibitory carotid sinus syndrome: Holter monitoring does not change the clinical selection of patients for treatment]. PMID- 4042578 TI - [Anti-platelet aggregation action and paradoxical effects of acetylsalicylic acid]. PMID- 4042580 TI - [Case of pseudohyperaldosteronism caused by 9-alpha-fluoroprednisolone abuse]. PMID- 4042581 TI - Symposium on nucleic acid probes and monoclonal antibodies in the diagnosis of infectious diseases. PMID- 4042582 TI - Osteoarthritis. PMID- 4042583 TI - On considerations of method and theory governing the use of clinical categories in neurolinguistics and cognitive neuropsychology: the case against agrammatism. PMID- 4042584 TI - Nutritional and lifestyle approaches to the prevention and management of hypertension. AB - We have been encouraged by the growing interest in nutrition and lifestyle for the prevention and treatment of hypertension. While no proven means for preventing hypertension exist, epidemiologic data have identified risk factors for hypertension. We have attempted to outline a reasonable program based on knowledge of risk factors for hypertension on one hand vs. the lack of data that hypertension can be prevented on the other. Managing patients who have hypertension with nondrug strategies is a different matter. First, more evidence is available indicating effectiveness for reducing a high pressure than for preventing a normotensive person from becoming hypertensive. Secondly, hypertension is a risk factor for premature cardiovascular morbidity and mortality. Thus, the risk-to-benefit ratio from intervening is tipped toward probability of benefit. Many of the nondrug therapies have been presented. It is unreasonable to expect a patient to adhere to every one. Therefore, patients with uncomplicated, newly diagnosed borderline and mild hypertension are given the range of modalities available and assisted in choosing those best suited to their lifestyle. The nondrug efforts are tried for three to six months in patients with uncomplicated mild hypertension. We advocate evaluating responses to the nondrug approaches with blood pressures measured both in and outside the office. Blood pressures measured by the patient at work and rest have been very valuable in our practice. If no antihypertensive benefit is seen, then most of these patients receive standard antihypertensive drugs. For those who have complete or partial success, the nondrug efforts are continued or reinforced with follow-up every three to six months.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4042585 TI - Dietary habits and blood chemistry levels of the stress-prone individual: the hot reactor. PMID- 4042586 TI - Aging and nutrition. PMID- 4042587 TI - Cardiovascular risks from very low calorie diets. PMID- 4042588 TI - Calories and chemically induced tumors in rodents. PMID- 4042589 TI - Iron deficiency and its functional consequences. PMID- 4042590 TI - Compliance in dietary management of hypertension. AB - Relapse is a problem common to all behavior-change programs, including weight reduction and salt-restriction programs. The process of relapse can be understood in the context of the way that emotional, social, and environmental forces impinge upon the individual's behavior. The data on compliance suggest that behavior modification programs are moderately efficient in producing changes in eating behavior. Relapse prevention programs are recommended as part of a dietary approach to the treatment of hypertension to increase treatment efficiency. If these programs are implemented using a group format, then these services can be delivered to patients at a reasonable cost. PMID- 4042591 TI - Nutrition and the elderly: helping the elderly help themselves. PMID- 4042592 TI - Carcinoma of the esophagus and cardia: current methods of treatment. PMID- 4042593 TI - Treatment of thyroid cancer. PMID- 4042594 TI - Diagnosis and treatment of thyroid nodules. PMID- 4042595 TI - Unconventional cancer therapy. PMID- 4042596 TI - Psychosocial considerations in the treatment of leukemia. PMID- 4042597 TI - Long-term effects of cancer chemotherapy. AB - As the management of advanced malignancy with multimodality therapy becomes more successful, the practicing general physician will see more chronic and late sequelae of therapy in the cured cancer patient. Chronic or late toxicities may occur in nearly every organ system. This article has briefly described the most common late toxicities that the practicing internist, pediatrician, family physician, and obstetrician/gynecologist should be prepared to recognize. PMID- 4042598 TI - Cancer screening: the primary care physician's role. PMID- 4042599 TI - Caring for patients with cancer: how stressful is it for the physician? PMID- 4042600 TI - In vitro formation of fine fibrils with a D-periodic banding pattern from type V collagen. AB - Type V collagen was isolated from human placenta by limited pepsin treatment and purified by salt fractionation. A solution of type V collagen was dialyzed at 4 degrees C against phosphate-buffered saline or against 0.02 M Na2HPO4. Aggregates formed under these in vitro conditions from a pure type V collagen solution were examined by electron microscopy. The aggregates were fine flexible fibrils. The fibrils formed during incubation at 25 degrees C were of relatively uniform diameter, 34.8 +/- 9.1 nm and did not show an axial banding pattern. When the specimen was incubated at 37 degrees C, the fibrils were of slightly larger diameter, 38.2 +/- 9.1 nm and almost all the fibrils had the axial repeat pattern of 67 nm. The ability of type V collagen to form banding fibrils is discussed in relation in the localization of the collagen in tissues. PMID- 4042601 TI - High post-translational modification levels in type II procollagen are not a consequence of slow triple-helix formation. AB - The kinetics of triple helix formation of newly synthesized type II procollagen in chick embryo sternal cartilage cells were determined. The data obtained were in agreement with a model for triple helix formation in cellulo proposed recently (Bruckner et al., 1981). The time required to produce fully triple helical type II procollagen in cartilage cells was only 30% longer than for type I procollagen in tendon cells. Therefore, the several-fold increase in post-translational modification observed for type II collagen as compared to type I collagen cannot be attributed solely to slow helix formation but rather is a result of higher levels of enzymic activity of post-translational modification present in cartilage cells. PMID- 4042602 TI - Electron microscopic demonstration of acid-labile, 4D-staggered intermolecular association of collagen formed in vitro. AB - The formation of acid-labile, unidirectional, and 4D-staggered dimers and polymers of collagen molecules in solutions at pH 4.0 and 4.5 has been demonstrated under the electron microscope. Collagen molecules extracted from lathyritic rat skin was dialyzed from 0.5 M acetic acid sequentially against 5-10 mM acetate buffer (pH 4-4.5) at 4 degrees C for 3-4 days, 0.3% glutaraldehyde in the same buffers for further 2 days, 0.5 M acetic acid, and then against 0.2% ATP X Na2/0.1 M acetic acid. Fibrous, unidirectional segment-long-spacing (SLS) forms were observed with 0.4D overlap between adjacent segments. Such a form was not observed when glutaraldehyde fixation step was omitted or when SLS was formed directly from the acidic solution; in both cases, monomeric SLS was only observed. It is concluded that collagen molecules, dispersed monomeric in acidic pH, form unidirectional linear dimers or polymers in which the molecules are associated with 0.4D overlap (4D stagger) at pH 4-4.5. PMID- 4042603 TI - Specific binding of collagen to Staphylococcus aureus. AB - In this study the specific binding of soluble type I collagen to several strains of Staphylococcus aureus was investigated. Both type I procollagen and soluble, pepsin-treated, lathyritic rat skin type I collagen bound to these bacteria in a manner which could be blocked by the addition of gelatin to the binding assay. Saturation binding studies showed more than one class of binding sites for [125 I]-lathyritic rat skin collagen to be present with each bacterium of the Cowan I strain containing approximately 135 high affinity sites with an apparent KA of 2.3 X 10(7)M-1. Like Cowan I strain, American Type Culture Collection (ATCC) strain 25923 also bound type I collagen. IgG inhibited collagen binding in a dose dependent manner. This observation together with the finding that the protein A deficient Wood strain did not bind collagen suggested that protein A might be the collagen binding site. However, failure of protein A-Sepharose to bind soluble collagen or protein A in solution to inhibit binding of collagen to Cowan I cells suggests that bacterial protein A does not mediate the binding. Addition of fibronectin to the binding assay did not affect the level of collagen binding, suggesting a) that the collagen binding site is different from the fibronectin binding site and b) that fibronectin does not mediate the binding of collagen to these cells. These results demonstrate a new example of bacterial binding to an extracellular matrix protein and suggest a possible mechanism whereby Staphylococcus aureus may adhere to mammalian tissue. PMID- 4042604 TI - Standard perinatal data: suggestions for regular review of facilities for perinatal care within a regional health authority. PMID- 4042605 TI - Monitoring preventive maternity and child health services in health authorities. PMID- 4042606 TI - The organization of district information services. PMID- 4042608 TI - How many districts have food and health policies? PMID- 4042607 TI - Accuracy of recall of surgical histories: a comparison of postal survey data and general practice records. PMID- 4042610 TI - What is under a blue flashing light? Community expressed need for the emergency ambulance service. PMID- 4042609 TI - A study of the nutrient content of hospital meals. PMID- 4042611 TI - Legionnaires disease in Reading--possible association with a cooling tower. PMID- 4042612 TI - A science lesson, a castor oil plant seed and a Salford schoolboy. PMID- 4042613 TI - Communicable disease report. January to March 1985. PMID- 4042614 TI - Contribution of nesting experience to progesterone-induced incubation in ring doves (Streptopelia risoria). AB - Injections of progesterone induce incubation behavior in gonadally intact ring doves only if the doves have had previous experience with at least the nest building phase of a breeding cycle. The present study was designed to determine whether exposure to progesterone during the nest-building phase is sufficient to account for the ability of progesterone to induce incubation at a later time or whether some other factor provided by experience with this phase of the cycle is needed. Six groups of 10 pairs of doves each were provided with different combinations of experience and progesterone priming. Progesterone priming combined with social isolation or with courtship experience had no significant effect on subsequent progesterone-induced incubation. However, doves that participated in the nesting phase of the cycle during progesterone priming later incubated in response to progesterone treatment. Nesting activity, which may or may not include building the nest, seemed to be the relevant experience. PMID- 4042615 TI - Ventral scent marking in Meriones unguiculatus may contribute to thermoregulation. AB - Three experiments were conducted with adult male Meriones unguiculatus in an attempt to demonstrate that ventral scent marking can act to transfer body heat to the object marked. Experiment 1 showed that surgical removal of the ventral gland pad reduced the amount of heat transferred by 50%, even though intact and glandless animals did not differ in the average frequency of scent marking. Experiment 2 demonstrated that the difference in heat transfer due to the presence or absence of the scent pad was not due to differential pressure applied to the substrate during marking. Experiment 3 showed that the pattern of ventral hair spread that occurs as an animal moves over an object is different between intact and glandless animals but that this difference does not account for the difference in heat transfer. It is suggested that heat transfer to the environment with ventral scent marking may increase thermoregulatory competence and also may function to volatilize sebum used in chemocommunication. PMID- 4042616 TI - Latent inhibition experiments with goldfish (Carassius auratus). AB - Evidence of latent inhibition was sought in a series of experiments with goldfish. In Experiment 1, goldfish were given nonreinforced preexposure to a color that subsequently predicted shock in an activity conditioning situation; their performance did not differ from that of control animals preexposed to a markedly different color. In Experiment 2, a group of goldfish given nonreinforced preexposure to a tone and an unstimulated control group were trained in an appetitive situation, with the tone serving either as a conditioned excitor or as a conditioned inhibitor. Preexposure had no significant effect in the conditioned excitation training, but it reduced the level of responding both to the positive stimulus and to the negative compound in the conditioned inhibition training. In Experiments 3 and 4, classical aversive conditioning was studied in the shuttle box. In Experiment 3, excitatory conditioning to a color was found to be impaired (relative to the performance of nonpreexposed control animals) as much by nonreinforced preexposure to the training color as by nonreinforced preexposure to a markedly different color; substantial variation in amount of preexposure was without significant effect. In the conditioned inhibition training of Experiment 4, animals with nonreinforced preexposure responded less than did unstimulated control animals both to the positive stimulus and to the negative compound. The results for goldfish can be understood on the assumption that the effect of preexposure in these animals is simply to reduce general responsiveness or level of arousal. PMID- 4042617 TI - Responsiveness to estrous chemostimuli in male rats (Rattus norvegicus) of different ages. AB - Previous findings indicate that Norway rats (Rattus norvegicus) respond differentially to estrous chemostimuli in early infancy and that adult male sexual responsiveness to such chemostimuli depends on infantile experience with suckling odors (Fillion & Blass, in press). The development of behavioral responsiveness to estrous chemostimuli in male rats from late infancy to adulthood was examined in this study. Preweanling, adolescent, and adult males were observed for 20 min in the presence of an anesthetized estrous or an anesthetized diestrous female. This was, for adolescent and adult subjects, the first heterosexual encounter since weaning. Rats in each age-group responded differentially according to female state, but in distinct, age-related ways. Preweanling spent more time investigating the female's body if she was estrous. Adults expressed the same affinity but by more focused investigation directed perivaginally. Adolescents showed no female-directed bias but groomed themselves more if the female was estrous. These data identify developmental continuities and discontinuities in male rat behavior toward sexually receptive females. PMID- 4042618 TI - Sex differences in urinary odors produced by young laboratory rats (Rattus norvegicus). AB - Responses of adult female rats to male and female pup urine were examined in three experiments. Investigatory sniffing of male and female pup urine deposits by maternal rats was compared in a series of simultaneous choice tests given at 3 day intervals between Day 2 and Day 17 postpartum. Male urine was consistently preferred. Introduction of male, but not female, pup urine to the nest was also found to significantly elevate maternal licking of anogenital regions of pups. Thus, urine from pups of various ages contains sex-identifying odors that differentially elicit spontaneous maternal interest. The odor of male urine may provide a sufficient stimulus to account for the greater anogenital licking that males of this species normally receive. Nonmaternal, naive, adult females behaved like maternal rats, preferring male urine in the choice test. This indicates that the maternal condition of a dam is not necessary either for the olfactory discrimination or for the male odor preference. PMID- 4042619 TI - Penile responses of rats (Rattus norvegicus) in extended ex copula tests. AB - Prolonged tests of rats' penile responses outside the context of copulation (ex copula) were undertaken to facilitate analysis of these penile components of copulatory behavior. Penile erections and flips were evoked for 1 hr following penile sheath retraction (SR), and rats were retested for 30 min after a rest interval of 5 min to 4 hr. The number of penile responses declined sharply over the course of the hour. Following a 5-min rest, there was little likelihood of additional responses. Within 2 hr some measures of penile response potential approached their original high asymptotes; other measures were still depressed after 4-hr rest. In control tests, the penile sheath was unretracted (SU) during the first 60 min, and hence few or no penile responses occurred. This condition caused no reduction in the number of erections and flips in the subsequent 30-min SR test; hence the reduction in response potential during and after SR tests was due to the responses displayed, not to the conditions of restraint. Ejaculation occurred frequently in the SU condition but rarely in SR tests, results suggesting that sheath retraction may normally inhibit ejaculation in ex copula tests, and perhaps during copulation as well. PMID- 4042620 TI - Kinship and affiliative behavior patterns in a captive group of Celebes black apes (Macaca nigra). AB - The influence of matrilineal kinship on four socially affiliative behavior patterns--grooming, contact, proximity, and play--was studied in a little-known primate species, the Celebes black ape (Macaca nigra). Twenty group-living black apes, comprising four genealogical groups, were observed for more than 100 hr; data were collected by the instantaneous scan technique. Animals spent more time than was expected by chance grooming, in contact with, and in proximity to their matrilineal relatives, but they did not play with relatives more than was expected. The proximal mechanisms responsible for these results are unknown, and increased familiarity among matrilineal relatives may have influenced the interaction patterns in the group. The results obtained in this study are similar to those of many others that demonstrate differential behavior toward kin, and they are consistent with the theory that animals may increase their inclusive fitness by interacting preferentially with relatives. PMID- 4042621 TI - NADH-ferrihemoglobin reductase in avian erythrocytes. AB - The assay for NADH-ferrihemoglobin reductase (NADH-FR) was optimized for avian blood samples. In this assay the pH optimum for Japanese quail red cell NADH-FR was 5.5, which was close to the enzyme's pI. Enzyme kinetic parameters were determined for quail, chicken and turkey NADH-FR. Preparation of erythrocyte ghost-cells and subsequent fractionation showed that the enzyme was present in the plasma membrane as well as in the nuclear membrane, while Triton X-100 treatment gave a release of enzyme activity from the membrane. In the cytosolar fraction of avian red cells no NADH-FR could be detected. PMID- 4042622 TI - Subcellular localisation of purine-metabolising enzymes in Leishmania mexicana mexicana. AB - Leishmania mexicana mexicana cultured promastigotes were fractionated by isopycnic centrifugation on linear sucrose gradients. Guanine, hypoxanthine and xanthine phosphoribosyltransferase activities were found to be associated with glycosomes, whereas adenine phosphoribosyltransferase was cytosolic. 3'- and 5' nucleotidases and IMP dehydrogenase were shown to be particulate, the former two possibly being associated with the plasma membrane, IMP dehydrogenase with the endoplasmic reticulum. Nucleosidases and deaminases were found to be cytosolic. The results demonstrate that intracellular separation of enzymes could play a part in the regulation of the parasite's purine metabolism. PMID- 4042623 TI - Isolation and characterization of deoxyribonucleic acid from tissue of the woolly mammoth, Mammuthus primigenius. AB - DNA was isolated from tissue samples of several mammoth specimens, radiocarbon dated between 10,000 and 53,000 years old. The DNA was purified by chromatography on hydroxyapatite at 60 degrees C and was characterized as a heterogeneous population of fragments ranging in size from 3000 to 200 base pairs. Thermal denaturation analysis demonstrated that approximately 25% of the DNA had a base composition similar to Asian elephant DNA calculated as 36% G + C. Preliminary analysis by nucleic acid hybridization indicated that only a small fraction of DNA isolated from mammoth tissue (2-5%) was homologous to DNA of Asian elephant, a close living relative of the mammoth. Our results provide the first definitive isolation and characterization of DNA from ancient tissue and suggest a purification strategy that will lead to preparations of DNA from mammoth tissue significantly enriched in elephant-related DNA sequences. PMID- 4042624 TI - Biochemical characterization of lysozymes present in egg white of selected species of anatid birds. AB - The isolation of lysozyme from the egg white of several representative species of waterfowl is described. The purified lysozymes were analyzed to determine the type and molecular weight of each enzyme. All enzymes found in duck egg whites were found to be of the c-type. In contrast all true geese, and the mute swan species as well as the northern blackneck screamer contain lysozyme g in their egg white. PMID- 4042625 TI - Isolation and characterization of metmyoglobin reductase from yellowfin tuna (Thunnus albacares). AB - The isolation, purification, and characterization of metmyoglobin reductase from yellowfin tuna (Thunnus albacares) is described. The enzyme has been purified 120 fold. Characterization of the enzyme includes molecular weight, isoelectric point, substrate specificity, enzyme kinetics, chromatographic behavior, and sensitivity to inhibitors. The physical and catalytic properties of the tuna enzyme are compared to those of bovine and blue-white dolphin metmyoglobin reductase. PMID- 4042627 TI - Ketogenic regulation by certain metabolites in rumen epithelium. AB - In experiments with rumen epithelium incubated in vitro in the presence of butyrate, the ketogenic effect of glucose was shared by epimeric monosaccharides but not by non-metabolizable analogues. 14C from glucose was not incorporated into ketone bodies. Malate increased ketogenesis from butyrate and decreased its oxidation, pyruvate and NH4+ had the opposite effect, and malonate inhibited both processes. The ketogenic effect of glucose was also effective with isovalerate maintaining the high proportion of acetoacetate which is characteristic of this substrate. Rumen epithelium transformed added acetoacetate into 3 hydroxybutyrate. It is concluded that reducing equivalents produced from glucose and other metabolizable substrates are responsible regulators of ketogenesis from butyrate. The results are discussed in view of the functional role of ruminal ketogenesis. PMID- 4042626 TI - An interspecies comparison of normal levels of glycosylated hemoglobin and glycosylated albumin. AB - Aminophenylboronic acid affinity chromatography was used to measure glycosylated hemoglobin and glycosylated albumin levels in a variety of species. The highest glycosylated hemoglobin levels were found in man, the lowest in the chicken and the pig. The highest glycosylated albumin levels were found in avian species, the lowest in the mouse and the rat. A simple kinetic model was used to analyze the rates of formation of glycosylated hemoglobin and albumin in the various species. Rates of glycosylated albumin formation were very similar across the species while rates of glycosylated hemoglobin formation were quite different, presumably reflecting wide differences in erythrocyte permeability to glucose among the species. PMID- 4042628 TI - Induction, isolation and a characterization of the lipid content of plasma vitellogenin from two Salmo species: rainbow trout (Salmo gairdneri) and sea trout (Salmo trutta). AB - Vitellogenin synthesis is induced in juvenile rainbow trout (Salmo gairdneri) and juvenile sea trout (Salmo trutta) by estradiol-17 beta. A purification procedure for vitellogenin from trout plasma by precipitation with MgCl2-EDTA and subsequent anion exchange chromatography on DEAE-Sephacel is described. The total lipid contents of purified rainbow trout and sea trout vitellogenins are 18 and 19%, respectively. Approximately 2/3 of the lipids are phospholipids, while the remainder consists of triglycerides and cholesterol. Phosphorus determinations on delipidated vitellogenin yield a phosphorus content of 0.63% in rainbow trout and 0.58% in sea trout vitellogenin. Native (dimeric) vitellogenins from rainbow trout and sea trout both have an apparent molecular weight of 440,000, when estimated by gel filtration on Sepharose 6B. PMID- 4042629 TI - Effects of temperature on glucose release and glycogen metabolism in isolated hepatocytes from rainbow trout (Salmo gairdneri). AB - Endogenous glucose release and glycogen metabolism were investigated in isolated hepatocytes from rainbow trout acclimated to 10 and 20 degrees C. Thermal acclimation did not significantly affect hepatocyte glycogen contents and the rates of glucose release during substrate-free incubations. In both acclimation groups glucose production and glycogen metabolism exhibited clearly different dependencies on assay temperature. It was concluded, that there are different sources of glucose release in the lower and upper temperature range- gluconeogenesis from endogenous precursors at low temperatures and glycogenolysis at high temperatures. This conclusion was supported by experiments with 3 mercaptopicolinic acid, which stimulated glycogen breakdown especially in the low temperature range. PMID- 4042630 TI - A model for L-lactate binding to Cancer magister hemocyanin. AB - L-Lactate raises the oxygen affinity of Cancer magister hemocyanin. The L-lactate analogs, D-lactate, glycolate and 2-methyl-lactate cause smaller increases in an oxygen binding affinity. Other analogs have no detectable effect. These data suggest that L-lactate binds to the hemocyanin at all four positions around the chiral carbon. The carboxyl and hydroxyl groups are required for activity. The protein can only partially distinguish between the methyl group and hydrogen atom. PMID- 4042631 TI - A comparison by HPLC of ferritin subunit types in human tissues. AB - Ferritin was isolated from human liver and spleen. Reversed phase high performance liquid chromatography of the ferritin subunits from each tissue yielded the same three chromatographic fractions. Physical and chemical characterization of the three fractions indicated that they represented at least two, perhaps three, chemically distinct subunits. PMID- 4042632 TI - Effect of denervation on the glycolytic metabolism of the main electric organ of Electrophorus electricus (L.). AB - Biochemical modifications of the glycolytic metabolism of the electric organ of Electrophorus electricus (L.) have been studied as a function of denervation. The activities of LDH, MDH and the concentrations of ATP, lactic and pyruvic acids were measured at intervals of zero, 15, 30 and 60 days following denervation. In parallel, CPK activity was also measured. All of these biochemical characteristics were substantially altered by denervation. The results obtained point to a change, after 15 days of denervation, from the normal anaerobic to an aerobic metabolism which remains after 30 days and reverts to anaerobic at 60 days. PMID- 4042633 TI - A computer-based data acquisition system for breathing and exercise entrainment studies. AB - An interactive, real-time, computer-based data acquisition system was designed to obtain data for breathing and exercise entrainment studies. By timing the steps of subjects walking on a treadmill relative to different points in the respiratory cycle (e.g. the beginning and end of inspiration), the relation between gait and ventilation can be followed on a breath-by-breath basis. Accurate establishment of the beginning and end of respiratory events from a pneumotachygraph signal was assured by using tidal volume thresholds for (1) noise, (2) minimum valid volume and (3) minimum duration. PMID- 4042634 TI - On the solution of equations for renal counterflow models. AB - The results of a comparative study of three discretization techniques and the solution of the resulting algebraic equations by three methods is given. For this study, a four-tube central core model with diffusion in the core was selected and equations were derived for a coherent and efficient implementation. The results of this study show that sparse matrix techniques that take the physiological connectivity of the kidney lead to significant savings in computer storage, running time and overall cost. PMID- 4042635 TI - Computerized EEG pattern classification by adaptive segmentation and probability density-function classification. Description of the method. AB - A phenomenological model for the representation of clinical EEGs is proposed. It assumes each individual record to consist of a few repetitive patterns which are described sufficiently by their power spectra. An algorithm for automatic EEG evaluation is described. It consists of two steps, a segmentation process which isolates the elementary patterns, and a clustering procedure which groups similar patterns with each other. Results are represented in graphical form. Diagnostic classification is not attempted. An appendix highlights the advantages of autoregressive modelling for EEG spectral analysis and, in particular, the estimation of the power contained in the various "rhythms". PMID- 4042636 TI - A new EDP assisted dietary survey employing a simple and concise data collection method. AB - The aim of the work was a diet analysis practice both accurate and simple to be used in daily applications. The subject records in real time his intake by employing the portion of food as unit of measure. Through the recipes, which may be obtained in deferred time, data are then reorganized by EDP to match food composition data of literature. A food composition table management system was developed which avoids vacancies of data: nine different sources from literature were used. The fact that the subjects records in a simple and concise way his intakes permits prolonged investigation: slight alterations of the diet are possible without changing his food preferences and with minimum reduction of compliance. PMID- 4042637 TI - Computer-assisted analysis of two-dimensional electrophoresis images using an array processor. AB - The CLIP4 machine has been used to analyze two-dimensional electrophoresis gel images. The architecture of the CLIP4 machine allows high-speed processing of gel images unavailable on conventional machines. The paper gives a brief review of the CLIP system followed by a detailed description of the segmentation and comparison algorithms. The segmentation algorithm makes full use of methods already designed for other gel analysis systems, but optimized for use on the highly parallel CLIP4 machine. The comparison algorithm is a totally new method using, to the full, the parallel efficiency of the CLIP4 computer. The algorithm attempts to match each spot on one gel with a corresponding spot on a second gel, operating simultaneously on all pairs of spots. PMID- 4042638 TI - Ridge regression and its application to medical data. AB - In this paper, data analysis techniques are employed to investigate the optimal properties of the ridge estimators and the stability of regression estimates. Numerical examples from the medical field are taken to compare the predictive ability of ridge regression analysis to that of ordinary regression analysis. PMID- 4042639 TI - Two-step estimators of the scale parameter of the Weibull distribution. AB - An efficient two-step method of estimating the scale parameter of the Weibull distribution is presented and compared to other estimation procedures. The shape parameter is obtained by a procedure other than maximum likelihood and then substituted into the maximum likelihood formula for the scale parameter. Three two-step and four one-step estimators were compared using a Monte Carlo simulation. When the shape parameter is less than one, the two-step estimator using a generalized least-squares estimate of the shape parameter was best in terms of observed relative efficiency. Maximum likelihood was best, but followed closely by the generalized least-squares estimator when the shape parameter is greater than one. PMID- 4042641 TI - Naphthol AS as a cause of pigmented contact dermatitis. AB - Naphthol AS is a coupling agent of cotton dyeing. 2 elderly women with hyperpigmentation of the neck and limbs are described. Both felt itching on the neck, forearms, and lower extremities and noted hyperpigmentation a month later. Both had worn cotton flannel nightdresses in winter. Patch testing with cotton flannel and methanol extracts were positive, but after estraction with methanol, the residual flannel did not react. The methanol extracts of cotton flannel, were analysed. The patients were tested with 5 extracted components; Naphthol AS was found to be the causative agent. PMID- 4042640 TI - Contact sensitivity in adults with atopic dermatitis in childhood. AB - 2 groups of patients were patch tested with a standard series of allergens. 1 group of 159 individuals aged 24-44 years had a history of severe atopic dermatitis, and the other group of 130 individuals in the same age range, had had moderate atopic dermatitis in childhood. In group 1, positive reactions were recorded in 17% and in group 2 in 23%. A significant difference in the % of individuals with positive reactions was found between those who had healed (9%) and those who had not healed (22%) before 15 years of age (P less than 0.05). The frequency of individuals with hand eczema in adult life was higher, but not significantly, among sensitized than non-sensitized individuals. Altogether 100 positive reactions were found in groups 1 and 2. The average number of positive reactions per person was significantly higher in individuals with than without hand eczema in adult life (P less than 0.05). The most frequent contact allergens were fragrance-mix, balsam of Peru and nickel, which had sensitized 8.0%, 4.5% and 4.1% of the individuals, respectively. PMID- 4042642 TI - Patch testing for nickel allergy. The influence of the vehicle on the response rate to topical nickel sulphate. AB - A group of 43 patients with a clinical history of nickel allergy who exhibited an equivocal or no allergic reaction to a patch test at 48 h were further challenged using several different formulations of nickel sulphate. This experimental test battery comprised aqueous, dimethyl sulphoxide (DMSO) and propylene glycol (PG) solutions of nickel sulphate, and nickel sulphate incorporated into cetomacrogol cream and yellow soft paraffin (PMF). Although some of these vehicles were irritant, a formulation-dependent test response was observed, such that in terms of the number of responses per unit weight of nickel sulphate applied to the skin, the vehicles could be ranked: DMSO greater than PG greater than aqueous solution greater than cetomacrogol cream greater than PMF preparations. This ranking could be correlated with the relative ease with which nickel sulphate could be dialysed from each vehicle in vitro. This study demonstrates that for nickel sulphate, the vehicle can influence the outcome of patch testing apparently by modifying the quantity of nickel released into the skin for elicitation of the allergic response. PMID- 4042643 TI - Inhibition of pyrethroid-induced paresthesia by scopolamine. PMID- 4042644 TI - Fiddler's neck and nickel dermatitis. PMID- 4042645 TI - Contact dermatitis to propolis. PMID- 4042646 TI - Irritant dermatitis due to Euphorbia marginata. PMID- 4042648 TI - Psychiatric diagnosis in DSM-III. PMID- 4042647 TI - Treatment of dermatitis from parthenin. AB - Composites and some other plants containing sesquiterpene lactones, frequently cause allergic contact dermatitis in man. No treatment is available to control this disease successfully. We have used an amino acid, cysteine, to treat allergic contact dermatitis in guinea pigs sensitized to parthenin, a major sesquiterpene lactone of an allergenic weed, Parthenium hysterophorus L. Cysteine treatment of the allergic reaction induced by parthenin resulted in (a) reduced time of recovery and (b) reduced intensity of the skin reaction. PMID- 4042649 TI - Guidelines for the pharmacological management of depression. PMID- 4042650 TI - Psychiatric triage. PMID- 4042651 TI - Ongoing intensive hospital treatment. PMID- 4042652 TI - The diagnosis and treatment of behavioral disturbances in the elderly. PMID- 4042653 TI - Private psychiatric hospitals in Connecticut: a tradition of excellence, a future of change. PMID- 4042654 TI - Current developments in the law: malpractice and informed consent. PMID- 4042655 TI - Computers in hospital management: patients, doctors, information and resources. PMID- 4042656 TI - Current status of therapeutic plasmapheresis and related techniques: report of the AMA Panel on Therapeutic Plasmapheresis. AMA Council on Scientific Affairs. PMID- 4042657 TI - Reflections on medicine. First the vision. PMID- 4042658 TI - Connecticut's living will statute. PMID- 4042659 TI - Norethisterone concentration in breast milk and infant and maternal plasma during ethynodiol diacetate administration. AB - Twelve women with established lactation of 4-8 weeks duration were given a low dose progestogen-only contraceptive, ethynodiol diacetate 0.5 mg (Femulen) daily. On the seventh and eight day of the study, prior to the mother's taking the pill, a blood sample was taken from her and from the infant. Further blood samples were collected from the mother 4 and 12 hours later. Breast milk samples were collected at every feed on day 7 and day 8. Ethynodiol diacetate is rapidly metabolised in humans, changing into the metabolite norethisterone which is found in both blood and milk. Hence, norethisterone concentrations were estimated. On day 7 and day 8, four hours after ingestion of the pill, the median norethisterone maternal plasma concentration was 1.60 ng/ml and it fell to a median level of 0.30 ng/ml prior to the next dose of the pill. At this time the median infant concentration was 0.10 ng/ml but the maximum observed level was 0.50 ng/ml. In the breast milk the norethisterone concentration appears to peak at around 4-8 hours following the ingestion of the pill. The maximum observed concentration in breast milk was 0.84 ng/ml. The amount of norethisterone ingested by the infant averaged 0.02% (6.65 micrograms) of the dose of ethynodiol diacetate ingested by the mother. The maximum observed on any one day was 0.07% (27.52 micrograms). The above results indicate that the amount of progestogen ingested by the infant from its mother's milk is small and is unlikely to pose a risk to the infant. PMID- 4042660 TI - Interaction of anticonvulsants and oral contraceptives in epileptic adolescents. AB - Oral contraceptives are in widespread use, and are commonly prescribed for contraception in patients taking other medications. An example of this is the concomitant use of oral contraceptives and anticonvulsants in epileptic patients. This combination creates a potential for drug interactions which may alter the efficacy of both medications. An apparent interaction between oral contraceptives and anticonvulsants was observed in this study of epileptic adolescent females. This interaction was evidenced by menstrual irregularities which occurred in 65% (7 of 11) of adolescents on both medications concomitantly. The frequency of irregularity was significantly higher in these adolescents when compared to adolescents on either medication alone. Irregularities appeared to be alleviated by increasing the strength of the oral contraceptive, and although a concern, the increased dosage did not affect seizure control. PMID- 4042661 TI - Effect of long-term hormonal contraception on plasma lipids. AB - Serum lipid and apoprotein levels were determined in fasting women after long term use (5-12 years) of Depo Provera, Orgametril, Ortho Novum SQ, Binordiol, Microgynon-50, and Ministat. Compared with matched controls, pure progestogens (Depo Provera and Orgametril) caused a moderate decrease of TG, HDL chol, and Apo A1, whereas estrogen-dominant oral contraceptives (Ortho Novum SQ) increased the same parameters. The effects of long-term use of hormonal contraception on lipids did not differ from those predicted from short-term (6 months) studies. PMID- 4042662 TI - A test of the National Death Index using the Coronary Artery Surgery Study (CASS). AB - The National Death Index (NDI) is a central, computerized index of death record information compiled from records submitted by the Vital Statistics Office of each state to the National Center for Health Statistics. A selection of 1180 cases, including 370 decedents, from the Coronary Artery Surgery Study was sent to the NDI to test the reliability of the index in identifying decedents. Five possible matching rules are considered: an NDI match with soundex included, an NDI match without soundex matches, an NDI match on social security number, an NDI match on personal data (first name, last name, sex, race, and month, day, and year of birth), and an NDI match on social security number or personal data. In determining death, the greatest positive predictive value was given by a match on social security number, while the greatest negative predictive value was given by an NDI match with soundex included. Further comparisons of sensitivity and specificity, and figures that relate predictive values to the population mortality rate, are given to assist potential users in determining an optimal matching rule. PMID- 4042663 TI - Adjusting for baseline measurements in the two-period crossover study: a cautionary note. AB - It is intuitively appealing in planning a two-period crossover study to have each patient measured on the response variable at the beginning as well as at the end of both periods, and to take the change from the value at the start of the period to the value at the end as the measure of the patient's response to the treatment given during that period. This apparently innocuous procedure may, contrary to one's intuition, produce bias in the analysis of the data for a difference between the residual effects and a difference between the direct treatment effects. PMID- 4042664 TI - Efficacy of topical chloramphenicol and tobramycin ophthalmic solutions in preventing severe Staphylococcus aureus keratitis in rabbits. AB - Various marketed chloramphenicol ophthalmic solutions were compared and various dilutions of Tobrex Ophthalmic Solution were tested for effectiveness in a Staphylococcus aureus rabbit keratitis model. Anesthetized rabbits were each infected intracorneally with 10(4) Staphylococcus aureus ATCC 29737 cells. Treatment groups consisted of five or six rabbits (10 or 12 eyes) per group. One group of rabbits was infected but not treated (Positive Control Group). Topical dosing of commercially available ophthalmic solutions was accomplished by depositing 0.1 mL of a color-coded test solution into the lower cul-de-sac of each eye. Dosing begin one hour after the mid-infection time and continued for a total of nine hourly treatments. Twenty-four hours after infection the rabbit eyes were graded (masked) using standard slit-lamp scoring procedures. The slit lamp scores for five of eight ocular parameters were used to calculate an eye score value for each rabbit eye. The five ocular parameters were selected, based on previous Stepwise Discriminant Computer Analysis of over 300 rabbit eyes infected with Staphylococcus aureus ATCC 29737 and treated with various antibiotics. The eye score values for each group were averaged and the treatments were compared for significant differences in efficacy using the nonparametric, Wilcoxon-Mann-Whitney Rank Sum Test.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4042665 TI - Fluorescence studies on tryptophan and sulfhydryl group changes of bovine lens crystallins in a photodynamic system. AB - Conformational changes in the three crystallins alpha-, beta-, and gamma- in a singlet-oxygen generating system were investigated by fluorescence studies of tryptophan and covalently-bound sulfhydryl probe 4-[(N-iodoacetoxy)N-methyl]amino 7-nitrobenz-2-oxa-1,3-diazole (IANBD). Upon excitation at 295 nm, the tryptophan emission maxima of the crystallins were red-shifted by irradiation with visible light in the presence of the photosensitizer methylene blue. beta- crystallin showed the largest shift (4 nm) of the emission spectrum. Time course of the fluorescence changes by irradiation showed that the decrease in the tryptophan fluorescence yield occurs most rapidly for beta-crystallins, as compared to alpha or gamma-crystallins. Fluorescence changes of IANBD-labeled crystallins show a 40% decrease in the fluorescence intensity of the sulfhydryl probe for beta crystallin after one hour of irradiation. For alpha- and gamma-crystallin smaller decreases (7% and 15% respectively) were observed. Since all the sulfhydryl groups of beta-crystallin are known to be exposed on the surface of the protein (Andley et al, 1982, Biochemistry 21, 1853), these results suggest that the pronounced changes in conformation of beta-crystallin by singlet oxygen may be due to a rapid loss of the protein tertiary structure by oxidation of the sulfhydryl groups. These results have potential significance in understanding the age and cataract-related changes in the ocular lens in view of the fact that several key lens enzymes are associated with beta-crystallins in vivo. PMID- 4042666 TI - Determination of bovine retinal melatonin with HPLC-EC. AB - Bovine retinae, devoid of pigment epithelium, were assayed for endogenous melatonin using high-performance liquid chromatography with electrochemical detection (HPLC-EC). A method of extracting the more polar biogenic amines and metabolites was employed, allowing for direct injection of retinal supernatants into the chromatographic column. THE RESULTS: 1) confirm the presence of melatonin in the bovine retina; 2) provide a "benchmark" of 3.01 ng/retina for normal adult retinae collected during photophase; and 3) indicate that HPLC-EC represents an adequately sensitive instrument for the detection and quantification of melatonin in a single bovine retina. PMID- 4042667 TI - Retinyl ester hydrolase of bovine retina and pigment epithelium: comparisons to the rat liver enzyme. AB - The hydrolysis of 3H-retinyl ester was examined in the retinal pigment epithelium (RPE) and neural retina of cattle eyes and compared to that in homogenates of rat liver. The optimum pH for hydrolysis was 4.0-4.5 for RPE and 7.5-8.0 for liver. The RPE activity, which shows no variability between individual animals, is localized mainly in the lysosomal fraction of the cell. It is strongly inhibited by bile salts at concentrations as low as 0.2-0.5% and conversely, is strongly activated by Triton X-100, with maximum stimulation found at a concentration of approximately 1%. The apparent Vmax for hydrolysis of labeled retinyl ester in the RPE is 2.7 nmoles/hr/mg protein, a value approximately 1/150 to 1/200 of the rate of retinol esterification in these cells. Little or no hydrolytic activity could be detected in neural retina or in rod outer segments. Studies on the specificity of the RPE retinyl ester hydrolase activity revealed unexpectedly high hydrolytic activity toward both cholesteryl oleate and triolein, approximately 20 and 5 times greater, respectively, than in rat liver. The hydrolytic activity for cholesteryl oleate in the RPE was mainly at pH 3.5, while that for triolein showed three pH maxima, one at pH 4.5-5.0, a second near neutral pH and the third at pH 8. These findings reflect an active and complex pattern of fatty acyl ester lipid-metabolizing enzymes in cattle RPE whose interrelationships to one another require further clarification. PMID- 4042668 TI - Electron microscopy of corneal surface microdiathermy. AB - Microdiathermy has recently been shown to be effective in the treatment of persistent corneal epithelial recurrent erosion. In order to determine the mechanism of action of microdiathermy on the anterior surface of the cornea, rabbit eyes were treated with microdiathermy and the course of corneal tissue repair studied by electron microscopy. Shortly after treatment, the epithelium is edematous and necrotic and the lamina densa is thickened. Within 24 hours, the epithelium appears healed and some hemidesmosomes are present, but the lamina densa is still thickened. At two weeks the epithelial surface is undulated and protrudes into the stroma in areas where the lamina densa is disrupted. Hemidesmosomes are absent in these regions. Activated fibroblasts are present in superficial stroma. At four weeks following microdiathermy, there is segmental deposition of new lamina densa and a connective tissue zone between the newly deposited lamina densa and the old lamina densa. Hemidesmosomes are present only in areas of newly deposited lamina densa. Between six weeks and three months the epithelial basal surface becomes more uniform with mature hemidesmosomes and the new lamina densa is complete. The old lamina densa remains below it but is no longer present by six months. The mechanism of action for microdiathermy in recurrent erosion is believed to be as follows: in the treated area, epithelium and activated fibroblasts secrete a new connective tissue layer, which provides a suitable substrate to which the epithelium can adhere until it secretes a new lamina densa and hemidesmosome formation can occur. PMID- 4042669 TI - Bovine lens calmodulin. Isolation, partial characterization and calcium independent binding to lens membrane proteins. AB - Calmodulin has been isolated from calf lens fiber cells. Like other vertebrate calmodulins lens calmodulin shows a calcium-dependent mobility shift on SDS polyacrylamide gels and forms immune complexes with antiserum, raised against vertebrate calmodulin. Via the gel overlay technique radioiodinated calmodulin from lens or bovine brain was found to bind to the main intrinsic protein (MIP) and the 17.5 kDa protein of lens fiber membranes in a calcium-independent manner. After proteolytic digestion of lens fiber membranes with trypsin or Staphylococcus aureus V8 protease the calmodulin-binding activity of MIP is retained. This result indicates that the small polypeptide fragment of MIP, which is accessible to proteolytic attack, apparently is not the attachment point for calmodulin. Two additional calmodulin-binding proteins (MW 14 kDa and 16.5 kDa) are observed in junction-enriched fiber membrane fractions. These junction specific proteins are bound to the membrane via calcium. In addition to MIP and the 17.5 kDa protein they are possibly involved in the calcium-dependent regulation of lens fiber junctions. The 14 and 16.5 kDa proteins are also present in epithelial membranes, prepared from freshly obtained calf lens epithelia. Whereas in the latter membranes the two proteins form part of the four 14-17 kDa major protein components, these proteins are absent in membranes from cultured lens epithelial cells. The epithelial 14 kDa and 16.5 kDa proteins thus appear to be junction-specific. The capacity of the latter proteins to bind calmodulin in the presence and absence of calcium indicates that these junction-specific proteins are very similar, if not identical, to the corresponding fiber junctional proteins.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4042670 TI - Neck dissection for cancer. AB - Control of metastatic disease in the neck is only a part of the spectrum of treatment of a patient with head and neck cancer. Concepts as to how to manage both the primary cancer and the possible metastases in the neck are constantly changing, and new combinations are being proposed almost daily. This article focuses mainly on the various surgical procedures that have been advocated in an attempt at controlling metastatic disease in the neck. The author has not considered the role of control of the primary cancer nor the significance of distant metastases in the rate of survival of patients with head and neck cancer. The frequency with which patients with cancer of the upper aerodigestive system develop second primaries indicates that we are only dealing with a portion of the problem. We have no way of reversing the premalignant changes that have probably developed in the epithelial surface of the smokers/alcoholics who constitute such a large percentage of the patients with whom we deal. PMID- 4042671 TI - The BALB/c mouse. Genetics and immunology. PMID- 4042672 TI - Immunoprophylaxis in BALB/c mice: a model for development of protection against primary and secondary infection with Leishmania major. PMID- 4042673 TI - Genetic control of systemic Leishmania major infection: identification of subline differences for susceptibility to disease. PMID- 4042674 TI - Susceptibility to Abelson or Moloney murine leukemia viruses. PMID- 4042675 TI - Differential susceptibility to experimental autoimmune orchitis in BALB/c substrains. PMID- 4042676 TI - Variation in responsiveness of BALB/c sublines and congenic mice to phase I Coxiella burnetii infection and vaccination. PMID- 4042677 TI - Pristane-induced arthritis in BALB/c mice. PMID- 4042679 TI - A series of recombinant inbred strains between the BALB/cHeA and STS/A mouse strains. PMID- 4042678 TI - Response of the peritoneal mesothelium to the mineral oil, pristane. PMID- 4042680 TI - Characteristics of the wm substrain of BALB/c mice. PMID- 4042681 TI - Genetic variation in catecholamine responsive metabolic pathways--a hypothesis for a common regulatory mechanism in BALB/c sublines. PMID- 4042682 TI - DNA hybridization subtraction: differences detected between BALB/cAnPt and BALB/cJax at the DNA level. PMID- 4042683 TI - Genetically contaminated BALB/c nude mice. PMID- 4042684 TI - Preferential nondisjunction of specific bivalents in oocytes from Djungarian hamsters (Phodopus sungorus) following colchicine treatment. AB - In an attempt to study the mechanisms leading to nondisjunction during meiosis I, Djungarian hamster females were treated with colchicine (3 mg/kg), which binds specifically to tubulin. The number of ovulated oocytes per female was significantly reduced following colchicine treatment (8.2 +/- 5.3, compared to 10.6 +/- 5.9 in controls receiving saline solution only). Application of colchicine rather late during oocyte maturation (ie, 5.5 h after injection of human chorionic gonadotrophin) caused a significant increase in the number of ovulated diploid (34.5%) and hyperhaploid (11.7%) oocytes, compared to the frequencies observed in the saline-treated controls (0.8% and 3.5%, respectively). Specific bivalents (viz, the large meta- and submetacentric chromosomes of groups A, B, and C) were preferentially involved in colchicine induced nondisjunction. The same pattern of chromosomal malsegregation was previously observed in oocytes from this hamster species following hypergonadotrophic stimulation. Preferential involvement of bivalents in the process of nondisjunction, whether induced by colchicine or hypergonadotrophic stimulation, is explained by an interference with microtubular function affecting those bivalents that are the last to segregate. PMID- 4042685 TI - Detection of Y-specific repeat sequences in normal and variant human chromosomes using in situ hybridization with biotinylated probes. AB - In situ hybridization with a cloned human Y-specific repeat, pY3.4, derived from the 3.4-kb HaeIII repetitive sequences, is useful in identifying Yq-autosome translocations. In this study nonradioactive procedures were also employed to detect the sites of hybridization. Using a biotinylated probe and either immunofluorescence or horseradish peroxidase reaction, the chromosomes of three probands and members of their families with probable Y-autosome translocations were examined. It was found that not all such translocations can be correctly diagnosed based on conventional banding analysis. The present data indicate the importance of chromosome-specific probes in studying chromosome rearrangements in man. PMID- 4042686 TI - Studies on endoreduplication. V. A three-dimensional scheme for diplo- and quadruple chromosomes and a model for DNA replication. AB - The metaphase appearance of quadruple chromosomes in colchicine-treated CHO cells was compared between air-dried and gently squashed preparations. A marked difference in morphology between the two methods suggested that the planar alignment of quadruple chromosomes is an artifact of the spreading process and that quadruple chromosomes are organized within the nucleus in a three dimensional configuration. By analyzing the alignment of the original and replicated strands, using BrdU incorporation, the three-dimensional orientation of the chromatids in quadruple chromosomes could be traced. This analysis led to a new model for DNA replication. According to this model, an opening of a DNA base pair which rotates about 90 degrees with respect to the deoxyribose phosphate backbone precedes DNA replication, resulting in the formation of the newly replicated strands perpendicular to the original plane of the base pair. This model, although derived from endoreduplication, may be applicable to a general scheme for DNA replication during normal chromosome duplication. PMID- 4042687 TI - Chromosomal evolution in Malagasy lemurs. VIII. Chromosome banding studies of Lepilemur ruficaudatus, L leucopus, and L septentrionalis. AB - The karyotypes of three Lepilemuridae species, Lepilemur ruficaudatus, L leucopus, and L septentrionalis, are described and compared. An almost complete analogy of chromosome banding is exhibited. Several complex chromosomal rearrangements, especially end-to-end translocations, have occurred in the evolution of these species. The chromosomal data indicate that the species studied are well separated. In addition, their common chromosomal characters show that they constitute a clearly distinct family among the lemurs. PMID- 4042688 TI - Assignment of the porcine major histocompatibility complex to chromosome 7 by in situ hybridization. AB - The major histocompatibility complex (SLA) of the domestic pig (Sus scrofa) was regionally mapped to 7p12----q12 by in situ hybridization with an SLA class I specific recombinant DNA probe. This localization contradicts linkage data suggesting a possible assignment of the SLA locus to porcine chromosome 15. PMID- 4042689 TI - Correlation between X-chromosome inactivation and cell differentiation in female preimplantation mouse embryos. AB - By means of a cytological method involving BrdU incorporation and acridine orange fluorescence staining in combination with embryo manipulation, we studied X chromosome activity in female preimplantation mouse embryos with special reference to the correlation between X-chromosome inactivation and cell differentiation. There was no sign of asynchronous replication between the two X chromosomes from the one-cell to intermediate blastocyst stage. The allocyclic X chromosome, first detected in late blastocysts, was paternal in origin, mostly replicating early in the S phase and limited to the trophectoderm. Subsequent X chromosome inactivation occurring in the primary endoderm was also characterized by the involvement of the paternal X and early replication. Both X chromosomes continued to replicate synchronously in the embryonic ectoderm or epiblast at this stage. It was evident that overt cell differentiation preceded the appearance of the asynchronously replicating X chromosome in the trophectoderm and primary endoderm. This finding seems to support the view that cell differentiation is an important correlate of X-chromosome inactivation. PMID- 4042690 TI - Localization of the alpha and beta casein genes to the q24 region of chromosome 12 in the rabbit (Oryctolagus cuniculus L.) by in situ hybridization. AB - The syntenic alpha and beta casein genes were localized in the rabbit by chromosomal in situ hybridization, using a mixture of two radioactive cDNA probes corresponding to these two genes. Highly significant labeling was observed on chromosome 12. A total of 175 silver grains was found on chromosomes in the 193 mitoses studied; 18% of the grains were on chromosome 12, and 42% of the grains on this chromosome were localized to the 12q24 region. Statistical analysis revealed that this labeling was highly significant. PMID- 4042691 TI - Assignment of uroporphyrinogen decarboxylase (UROD) to the pter----p21 region of human chromosome 1. AB - The assignment of the human gene for uroporphyrinogen decarboxylase (UROD) to chromosome 1 is confirmed and further localized to the pter----p21 region through the use of human-mouse somatic cell hybrids. Human and mouse UROD were separated by electrophoresis and identified with antibodies to the human enzyme after electrophoretic transfer to nitrocellulose membranes. PMID- 4042692 TI - Effects of the male contraceptive agent gossypol on meiotic chromosomes of the male rat. AB - Synaptonemal complexes (SCs) of rat spermatocytes were analyzed in silver-stained meiotic preparations 10-24 days after treatment with gossypol acetic acid, 30 mg/kg/day, for 70 days. Gossypol did not affect SC formation or function, as judged by the absence of pairing anomalies, SC fragmentation, or presynaptic arrest. The unpaired lateral axes could be seen at zygotene, and at pachytene normal SCs could be observed. The behavior of the XY axes also appeared to be normal. PMID- 4042693 TI - The structural gene for human coagulation factor X is located on chromosome 13q34. AB - The gene coding for coagulation factor X was studied in a family segregating chromosomal abnormalities involving chromosomes 13 and 6. An individual monosomic for 13q34 was deficient in levels of clotting factors VII and X, while her brother, who is trisomic for 13q34, had elevated levels. DNA dosage studies with a cloned human factor X gene demonstrated that the low levels of factor X expression in the individual with the chromosome 13q34 deletion were due to the absence of one copy of the factor X structural gene. This confirms the assignment of the human gene coding for factor X to 13q34. PMID- 4042694 TI - Familial reciprocal translocation t(1;4)(q31;p15) traced through five generations. PMID- 4042695 TI - Cystic fibrosis: analysis of linkage of the disease locus to red cell and plasma protein markers. PMID- 4042696 TI - Endometrial carcinoma. A retrospective, epidemiological study. AB - In a retrospective, epidemiological study of 414 patients with endometrial carcinoma, 73.4 percent were overweight and 55.8 percent were obese. The patients had a significantly greater absolute and relative weight than normal control subjects. A tendency was also apparent for height to be greater than in the controls. The patients had low fertility, early menarche and a tendency to late menopause, as well as a considerable premorbid consumption of estrogen preparations. Another characteristic of the patients was their low social class. The aetiology of endometrial carcinoma is presumably multifactorial. Long-term or increased estrogen stimulation of the endometrium plays a role, possibly potentiated by absence of progesterone influence. Obesity contributes to elevated estrogen level by the conversion of androstenedione to estrone in the fatty tissue. The diet depends on the social background and is significant for the development of obesity. Obesity, together with the amount and the composition of the food consumed, might predispose to endometrial cancer by elevated production of endogenous estrogen. PMID- 4042697 TI - Intravenous methylprednisolone pulse therapy in ankylosing spondylitis. AB - For several years the medical treatment of active ankylosing spondylitis (AS) has been NSAID because gold, penicillamine, antimalarials and steroids have been without efficacy. In 1981, Mintz et al reported that methylprednisolone pulse therapy (MPPT) had an excellent effect in patients with AS. Seven patients with active AS and insufficient efficacy of NSAID for three months were treated with one gram methylprednisolone daily given intravenously for three successive days. Mobility and pain were recorded before, during, and after treatment. Significant pain relief and improvement of mobility of the spine for at least six weeks were clearly demonstrated (p less than 0.05). Finger to floor distance and chin manubrium distance improved significantly for at least six months (p less than 0.05). We conclude that intravenous MPPT is a useful treatment in patients with active AS when NSAID is insufficient. PMID- 4042698 TI - Visceral artery aneurysms. A review. AB - Although rare, visceral artery aneurysms are reported with increasing frequency, mostly as a result of the growing use of angiography in unclear cases of abdominal symptoms. The splenic artery aneurysms are by far the most common, followed in frequency by the renal and hepatic artery aneurysms. The splenic and renal artery should undergo surgery in all cases of symptomatic aneurysms, asymptomatic aneurysms discovered in pregnant women or women of child-bearing age, aneurysms with documented growth, and aneurysms with a diameter more than 2 cm. The hepatic artery aneurysms as well as the more rare aneurysms should be treated surgically as soon as the diagnosis is established because the natural course of these aneurysms seems to be progression to rupture. In high risk patients, transcatheter arterial embolisation has recently proven to be a useful alternative to surgery in many cases. PMID- 4042699 TI - Lieutenant of the men of death. PMID- 4042700 TI - Alterations of pulmonary epithelial permeability caused by smoking and other injuries to the lungs. PMID- 4042701 TI - Osler-Charcot disease. A new title for an old friend. PMID- 4042702 TI - William Tell and technology. PMID- 4042703 TI - Reliability of the bronchoscopic protected catheter brush in intubated and ventilated patients. AB - The reliability of a bronchoscopic protected catheter brush (BPCB) in the diagnosis of lower respiratory tract infection was studied in 17 intubated and ventilated patients, including seven patients free from such infection (group 1) and ten patients with suspected infection (group 2). A first sample was obtained in the lower trachea by aspiration through the fiberoptic bronchoscope and a second in a distal bronchus by the BPCB procedure. In group 1, all BPCB cultures were sterile, although lower tracheal cultures yielded two or more bacterial species, showing that uncontaminated specimens can be obtained by the BPCB procedure. In three patients of group 2, BPCB cultures remained sterile as a nonbacterial pulmonary disease was certified by open lung biopsy. In seven patients from group 2, BPCB cultures yielded all of the organisms isolated simultaneously by reference methods (ie, cultures of blood or pleural fluid, serologic tests, and open lung biopsy). In two of these patients, contamination of the BPCB specimens was ascertained by the reference method bacterial results. In this study the BPCB procedure was able to obtain uncontaminated specimens in intubated and ventilated patients and was mainly accurate in identifying the bacterial etiologic agents of lower respiratory tract infections. PMID- 4042704 TI - Abnormal septal Q waves in sickle cell disease. Prevalence and causative factors. AB - Electrocardiograms and M-mode echocardiograms were obtained prospectively from 72 patients with hemoglobin SS (n = 55) or SC (n = 17) disease to assess the prevalence of abnormal Q waves in sickle cell disease and to determine if such Q waves could be explained by, or related to, echocardiographically determined anatomic or functional abnormalities. The mean age (+/- SD) of the population under study was 28 +/- 9 years, and the mean hematocrit reading was 28 +/- 5 percent; 43 male and 29 female patients were evaluated. No patient had a history of systemic arterial hypertension, valvular heart disease, or congestive heart failure. Abnormal septal Q waves (amplitude greater than or equal to 0.30 mV; duration less than or equal to 29 msec) were noted in leads V4, V5, or V6 in 15 of 72 patients, and 50 percent (36) of the population under study demonstrated electrocardiographic voltage changes consistent with left ventricular hypertrophy. M-mode echocardiography showed that 29 of 72 patients had a thickened interventricular septum (greater than or equal to 1.2 cm), 16 of 72 had an abnormally thickened left ventricular posterior wall (greater than or equal to 1.2 cm), and 31 of 72 had increased left ventricular mass (greater than 215 g). The prevalence of electrocardiographic and echocardiographic abnormalities was not significantly different between patients with hemoglobin SS and SC disease. Septal excursion was decreased in 11 of the patients, and global left ventricular function (percent fractional shortening) was slightly decreased in three patients. Regional wall motion was normal in all 72 patients. Six percent (four) of the patients met echocardiographic criteria for asymmetric septal hypertrophy. Linear regression analysis yielded significant positive correlations between septal dimension (r = 0.38; p less than 0.001) and left ventricular mass (r = 0.37; p less than 0.005) when each was compared with Q-wave amplitude. A significant negative correlation (r = 0.40; p less than 0.001) was noted between hematocrit reading and Q-wave amplitude. We conclude that abnormal septal Q waves are common in sickle cell disease and are related, in part, to septal thickness, as well as left ventricular mass and degree of anemia. PMID- 4042705 TI - Transbronchial biopsy in the thrombocytopenic patient. AB - Twenty-five flexible fiberoptic bronchoscopic procedures with transbronchial lung biopsies were performed in 24 severely thrombocytopenic immunocompromised patients (mean platelet count of 30,000/cu mm, with a range of 7,000/cu mm to 60,000/cu mm) during the diagnostic evaluation of pulmonary infiltrates. Three patients had self-limited endobronchial bleeding. A single death was attributable to massive hemorrhage after transbronchial biopsy and brushing. Specific etiologic diagnoses were established by bronchoscopy in nine cases. PMID- 4042706 TI - The relationship between functional class and cardiac performance in patients with chronic aortic insufficiency. AB - We have evaluated the relationship of New York Heart Association functional class (FC) assessment to rest and exercise hemodynamics and resting left ventricular (LV) functional data in 75 consecutive patients with isolated, chronic aortic insufficiency. Although there was a tendency for hemodynamic and angiographic variables to worsen as FC increased there was considerable overlap between patients assigned to the various groups. Statistically significant differences were seen only for resting left ventricular end-diastolic pressure (LVEDP) and pulmonary artery wedge (PAW) pressure which were higher in FC 3/4 patients than in FC 1 or 2 patients. The results of our study suggest that FC assignment cannot be used to accurately define underlying LV performance or hemodynamics in an individual patient with chronic aortic insufficiency. However, since severe abnormalities are unlikely to be present in asymptomatic patients, routine detailed frequent investigation does not seem warranted in this group. As FC worsens, the likelihood of left ventricular dysfunction increases. Thus, the presence of symptoms is an indication for more extensive evaluation. PMID- 4042707 TI - Increase in PaO2 following intravenous administration of propranolol in acutely hypoxemic patients. AB - To define the effects of beta-blockade therapy on PaO2, arterial blood gas levels were determined before and after therapeutic administration of propranolol in 44 acutely ill patients. With a FIo2 of 0.33 +/- 0.08, the PaO2 increased from 89.6 +/- 3.6 to 95.3 +/- 3.8 mmHg (p less than 0.01), 10 minutes after intravenous administration of 1 to 3 mg of propranolol. Simultaneous hemodynamic measurements obtained in six patients demonstrated a dramatic decrease in venous admixture, associated with decreases in cardiac output and mixed venous Po2. Propranolol administration generally results in a moderate increase in PaO2, which is related to a significant decrease in pulmonary shunt. The clinical implications of these findings are limited by the expected decrease in tissue oxygen delivery after beta-blockade therapy. PMID- 4042708 TI - Early neutrophil alveolitis after antigen inhalation in hypersensitivity pneumonitis. AB - Bronchoalveolar lavage (BAL) was carried out before and after antigen inhalation in ten hypersensitivity pneumonitis (HP) and five control subjects. Control subjects did not show any significant variation in BAL cells after challenge with diluted pigeon serum. In HP patients, the total number of BAL cells increased from (41.5 +/- 16.8) X 10(4) cells/ml before challenge to (84.0 +/- 28.9) X 10(4) cells/ml after challenge. Of greater interest, the values of polymorphonuclear neutrophils in patients increased from 8.3 +/- 9.7 percent before challenge to 41.2 +/- 24.35 percent, 24 hours after antigen challenge (p - 0.0001). Another BAL, carried out a week later, recovered a persistently high number of cells, (74.67 +/- 33.36) X 10(4) cells/ml. However, the percentage of polymorphonuclear neutrophils and lymphocytes did not differ from the initial pre-challenge BAL. Our study demonstrates an immediate and transient neutrophil alveolitis after antigen inhalation in patients with acute hypersensitivity pneumonitis. PMID- 4042709 TI - Complications of right heart catheterization. A prospective autopsy study. AB - The purpose of this study was to characterize the type and prevalence of abnormalities associated with right heart catheterization. We performed detailed post-mortem examinations of 32 consecutive patients brought to autopsy with a right heart catheter in the pulmonary artery. Thrombosis (17 patients, 53 percent), hemorrhagic lesions (25 patients, 78 percent), and intimal fibrin deposition (21 patients, 66 percent) were found at sites along the entire path of the catheter. Twenty-nine patients (91 percent) had either thrombosis, hemorrhage or both. While the superior vena cava was the most common site for all lesions, seven patients had thrombosis involving the chambers and valves of the heart and four had thrombosis involving the pulmonary artery. The incidence of thrombosis was significantly higher after 36 hours of catheterization (p less than 0.05). All five patients with thromboemboli in the more proximal pulmonary arteries had catheter-related thrombosis. We conclude that there is a high prevalence of thrombotic and hemorrhagic lesions in patients dying with pulmonary catheters in place; that the risk of thrombotic complications increases with duration of catheterization; and that patients with catheter-related thrombosis are at increased risk of thromboemboli to the proximal pulmonary arteries. PMID- 4042710 TI - Transbronchial fine needle aspiration of bronchogenic cysts. AB - Transbronchial fine needle aspiration (TBFNA) was used to confirm the diagnosis of bronchogenic cyst in two asymptomatic patients with mediastinal masses who declined surgical exploration. Both masses were located subcarinally but differed in computed tomographic density (7 and 59 Hounsfield units). Aspirate cytology demonstrated predominately bronchial columnar epithelial cells in mucus, without the lymphocytes and polymorphonuclear leukocytes normally seen in intrabronchial secretions. The denser cyst additionally contained some alveolar macrophages with ingested surfactant. While benignity cannot be absolutely assured, it is corroborated by serial evaluation of these patients, which has revealed no interval change in symptoms or roentgenographic size for two and three years, respectively. Under selected circumstances, it appears that TBFNA can be used to extend bronchoscopic diagnosis to benign mediastinal masses if the cytologic features of such aspirates are unique. PMID- 4042711 TI - Oral sustained-release aminophylline and bronchodilator response to inhaled fenoterol in patients with chronic airflow obstruction. AB - The bronchodilator response to inhaled fenoterol (400 micrograms) was examined in the morning and in the afternoon before and during oral sustained-release aminophylline treatment in eight patients with chronic reversible airway obstruction. Bronchodilatation was evaluated by measuring serial peak expiratory flow rates (PEFR) for eight hours after inhaled fenoterol and calculating the area under the time-response curves and the percentage increment from the baseline values. The patients showed an enhancement of the bronchodilatation achieved with fenoterol in the morning during aminophylline treatment. In the afternoon, instead, the effect of the fenoterol was not improved by oral aminophylline. This different effect of oral aminophylline might depend on the variable degree of potential reversibility present or diurnal variation in the bronchial response. PMID- 4042712 TI - Rapidly cavitating nodules in a young man. PMID- 4042713 TI - Keeping abreast of clubbing. PMID- 4042714 TI - Is the stepped-care approach to the management of hypertension still appropriate? PMID- 4042716 TI - An unusual echocardiographic finding in a ruptured sinus of Valsalva aneurysm. AB - A patient with a ruptured sinus of Valsalva aneurysm (RSVA) demonstrated an unusual two-dimensional echocardiographic manifestation of this entity. A discrete mass of echoes, appearing attached to a posterior leaflet of the tricuspid valve, moved to and fro into the right ventricle during diastole and into the right atrium in systole. This echocardiographic appearance mimics a vegetation of the tricuspid valve, a flail tricuspid leaflet, a right atrial myxoma or a pedunculated right atrial thrombus. Therefore, the differential diagnosis of this echocardiographic finding should include RSVA in addition to the above mentioned disorders. PMID- 4042715 TI - Amiodarone pulmonary toxicity. Assessment by bronchoalveolar lavage. AB - Bronchoalveolar lavage was used to demonstrate morphologic changes in alveolar macrophages characteristic of amiodarone effect in lung tissue obtained by biopsy. This procedure may be useful in the assessment of abnormal chest x-ray findings in patients suspected to have amiodarone toxicity. PMID- 4042717 TI - Endoscopic treatment of a whistling middle-lobe bronchus. AB - A 32-year old man presented with dyspnea and a loud inspiratory wheeze. Examination revealed a nonfibrous, fissure-shaped entrance to the middle-lobe bronchus. The cause of this stenosis was unclear. Endoscopic treatment consisted of splitting the spur and resulted in complete disappearance of the wheeze. PMID- 4042719 TI - Risks and benefits of peritoneal dialysis. PMID- 4042720 TI - Pulmonary edema and upper airway obstruction. PMID- 4042718 TI - Upper airway obstruction secondary to acquired immunodeficiency syndrome-related Kaposi's sarcoma. AB - A 45-year-old man with a history of intravenous drug use presented with acute respiratory distress. A pulsus paradoxus of 42 mm Hg, accessory respiratory muscle use and stridor were present. Examination of the oropharynx revealed multiple 1 to 2 cm purple lesions of the gingiva and hard palate. A purple tumor mass in the posterior pharynx obstructed the view of the larynx. An emergency tracheostomy was performed resulting in hemorrhage into the respiratory tract. Autopsy revealed disseminated Kaposi's sarcoma and large blood clots in the trachea and main stem bronchus. This case illustrates the occurrence of life threatening involvement of the upper aerodigestive tract with Kaposi's sarcoma and hemorrhagic complications resulting from surgical manipulation. PMID- 4042721 TI - Isoxsuprine and pulmonary edema. PMID- 4042722 TI - Ventricular tachycardia-like complexes in acute myocardial infarction. PMID- 4042723 TI - Pulmonary vascular smooth muscle and its interaction with endothelium. Morphologic considerations. AB - In pulmonary arteries the medial smooth muscle cells and endothelial cells, though separated by an internal elastic lamina, come into contact by way of fenestrations in this lamina. Such a continuous elastic lamina is absent in pulmonary veins facilitating this contact. If vasoconstriction is induced in experimental animals, herniations of medial smooth muscle cells protruding toward endothelial cells provide an extensive and close association and thus a potential interaction between both cell types. This is particularly prominent in the veins. In arteries these herniations, which must penetrate the fenestrations in the elastic lamina, are far less conspicuous. Intimal fibrosis, for instance, as an age change, is not necessarily an impediment for such interaction, since the cells within the intimal layer have all the characteristics of smooth muscle cells and thus may provide a smooth muscle-endothelium contact. PMID- 4042724 TI - Relevance of endothelial surface structure to the activity of vasoactive substances. AB - Increasingly it appears that expressions of vascular reactivity depend to a significant degree on reactions that occur on or near the endothelial surface. While the full scope of such reactions is not yet clear, some are now understood in terms of ultrastructural specializations of endothelium. PMID- 4042725 TI - Peptides, endothelium, and pulmonary vascular reactivity. AB - The lung contains a number of active peptides that can influence endothelial and smooth muscle function. At least two of these peptides are metabolized by endothelium, and endothelium is required for the vasodilator action of several peptides. A vasodilator peptide, VIP, may be the transmitter of the nonadrenergic, noncholinergic system, the major component of neurogenic relaxation of pulmonary vessels. PMID- 4042726 TI - Calcium kinetics in vascular smooth muscle. AB - The accumulation, binding, and mobilization of Ca++ in vascular smooth muscle directly affects intracellular free Ca++ levels and contractility. Techniques have been developed to delineate Ca++ uptake and efflux parameters in isolated vessels. Similar Ca++-related components are present in different types of vessels, but their relative importance for induction and maintenance of tension differ. PMID- 4042727 TI - Smooth muscle contractility. Effects of hypoxia. AB - Mechanical perturbation of smooth muscle provides information about the mechanical properties of its crossbridges. We have developed a method for identifying: (1) that normally cycling and very slowly cycling are sequentially activated, (2) the moment of this transition, and (3) the proportions of the two types of bridges recruited. Hypoxia decreases muscle shortening ability before isometric force. The former is due to depression of activity of both types of bridges. PMID- 4042728 TI - Effect of oxygen concentration on cellular metabolism. AB - Experimental evidence is presented that mitochondrial oxidative phosphorylation is dependent on oxygen concentration in its physiologic range both in vivo and in vitro. Mitochondrial oxidative phosphorylation is considered to act as a tissue oxygen sensor important for controlling local vascular resistance. PMID- 4042729 TI - The site and mechanism of oxygen sensing for the pulmonary vessels. AB - Lung vessels are unique in the body in that they react to hypoxia with constriction rather than dilatation. Whether this characteristic is inherent in the lung vessel or is due to an influence from a sensor in the surrounding lung parenchyma is not resolved. Recent data, however, showing that vascular hypoxia as well as airway hypoxia can produce pulmonary vasoconstriction and that the sensor for alveolar hypoxia is upstream in the precapillary vessels, allows but does not prove the precapillary pulmonary artery itself to be the O2 sensor. In addition, with the elimination of the mast cell as a necessary extravascular sensor for hypoxia at least in the mouse, there is no good candidate for an extravascular sensor for hypoxic pulmonary vasoconstriction. PMID- 4042730 TI - Site of hypoxic pulmonary vasoconstriction. PMID- 4042731 TI - Pulmonary gas exchange and exercise performance in pulmonary hypertension. AB - Patients with pulmonary hypertension have disordered pulmonary gas exchange and impaired exercise tolerance. The hypoxemia is due to mild ventilation-perfusion (VA/Q) inequality exaggerated by the presence of a low mixed venous PO2 (PvO2) and is accentuated during exercise due to a further fall in PvO2. This in turn may be worsened by vasodilators which increase the degree of VA/Q inequality. Decreased exercise tolerance is due predominantly to cardiac limitation, and thus an improvement in cardiac function subsequent to successful vasodilation can be assessed by improved exercise performance. PMID- 4042732 TI - Calcium channel blockers in primary pulmonary hypertension. AB - The demonstration that the calcium channel blockers reduce pulmonary vasomotor tone in experimental models of pulmonary hypertension has served as the rationale for their use in the management of primary pulmonary hypertension. The three currently available agents, verapamil, nifedipine, and diltiazem, have varying degrees of pulmonary vasoactivity. Experience with their use is reviewed. PMID- 4042733 TI - Use of calcium channel blockers in hypoxic lung disease. AB - COPD patients who are hypoxic develop pulmonary hypertension primarily because alveolar hypoxia induces muscular hypertrophy of pulmonary arteries. This muscular hypertrophy will regress in animals if they receive continuous oxygen therapy. Since many COPD patients refuse to use oxygen continuously, calcium channel blockers, which inhibit hypoxic pulmonary vasoconstriction, may be effective adjuvant therapy. Nifedipine lowers pulmonary vascular resistance during rest and exercise in hypoxic COPD patients. PMID- 4042734 TI - The role of vasodilators in patients with progressive systemic sclerosis. Interstitial lung disease and pulmonary hypertension. AB - The use of systemic vasodilator drugs in reducing pulmonary artery pressures in patients with pulmonary hypertension is controversial. The effect of hydralazine in four patients with pulmonary hypertension resulting from interstitial lung disease (group 1) and nifedipine in four patients with pulmonary hypertension secondary to progressive systemic sclerosis (group 2) was investigated. Hydralazine blunted exercise induced elevations in pulmonary arterial pressures in individual group 1 patients; nifedipine failed to effect significant salutory hemodynamic changes in any group 2 patients. PMID- 4042735 TI - Does pulmonary vasoconstriction play an important role in patients with primary pulmonary hypertension? A skeptic's view of vasodilator therapy. AB - Despite isolated reports of dramatic hemodynamic and clinical improvement over the past 30 years, most patients with primary pulmonary hypertension fail to benefit from treatment with vasodilator drugs and many develop serious adverse reactions. The failure of this approach strongly suggests that pulmonary vasoconstriction does not play an important role in the pathogenesis of this disorder. PMID- 4042736 TI - Dysphoric mood in young children referred to a child development unit. PMID- 4042737 TI - Mentally retarded teenagers: adolescent behavior disturbance and its relation to family environment. PMID- 4042738 TI - Normal and bright children of mentally retarded parents: the Huck Finn syndrome. PMID- 4042739 TI - Socio-psychosomatic dysfunctions: a case study. PMID- 4042740 TI - A psychological profile of juvenile firesetters in residential treatment. AB - Psychological test data of 30 known juvenile and adolescent firesetters were compared with those of a matched control group, within a residential treatment center, to distinguish the identifying characteristics of each group. Hypotheses based on 80 variables found in the literature on firesetting were treated by using a standard test equivalent for each variable. Of the hypotheses, 14 were found to differentiate significantly the two groups, but not all in the predicted direction. Four characteristics were found to be sufficient to discriminate between the groups with greater efficiency than any other combination of variables. A predictor equation is set forth. PMID- 4042741 TI - Reducing child abuse through respite center intervention. AB - Emergency respite care for children is shown to be effective in reducing stress on parents that can result in child abuse. PMID- 4042742 TI - Behavioral treatment of failure-to-thrive in a two-year-old. AB - Behavioral intervention was undertaken with a 2-year-old suffering from severe failure-to-thrive because it appeared that damaging feeding behaviors could be controlled. Altering the social patterns at mealtimes brought about gains in calorie intake and weight that continued through a 7-month follow-up period. PMID- 4042743 TI - A new multidimensional measure of children's perceptions of control. AB - Perceived control plays a central role in many motivational and cognitive accounts of behavior. In this study, a new 48-item self-report instrument, the Multidimensional Measure of Children's Perceptions of Control, is described. Perceptions of control are defined as children's understanding of the locus of the sufficient cause for success and failure outcomes. 3 dimensions of third- through ninth-grade children's perceptions of control are independently assessed: internal, powerful others, and unknown. Each of these sources of control is assessed within 3 behavioral domains: cognitive, social, and physical. General items are also included. Perceptions of control over success outcomes and failure outcomes are assessed separately. The psychometric properties of the new measure's subscales are presented. Correlations of the new measure with measures of perceived and actual competence and findings demonstrating the sensitivity of the new measure to developmental, gender, and environmental influences are reported. It is argued that the new measure is an advance over existing measures of internal versus external locus of control in children because it provides domain-specific assessments of 3 separate dimensions of locus of control, including the previously untapped dimension of unknown control. PMID- 4042745 TI - Optimality versus complications: assessing predictive values of perinatal scales. AB - In this study, 2 optimality scales and 3 complication scales were used to obtain perinatal risk scores for 103 infants. The scores generated by the 5 scales were compared for accuracy in predicting a variety of traditional and frequently used neonatal and infant outcome measures. The results were interpreted as showing an advantage in favor of the 3 complication scales in the number and variety of outcome measures that could be predicted from the scale scores. PMID- 4042744 TI - Repeated-measures analysis of variance in developmental research: selected issues. AB - This paper presents a review of recent developments in statistical techniques for repeated-measures analysis of variance. Since the literature has emphasized the issue of mixed model assumptions and their violation, we present an updated perspective on the nature of these assumptions and their implications for mixed model, adjusted mixed model, or multivariate significance tests. However, the central theme of the review is that the validity of mixed model assumptions is but one consideration in selection of an appropriate method of repeated-measures ANOVA. In particular, we recommend the avoidance of omnibus significance tests in favor of specific planned comparisons whenever hypotheses more specific than the omnibus null hypothesis may be formulated a priori. The analyst must also consider whether multiple dependent measures are to be analyzed, and the paper discusses alternative approaches to true multivariate repeated-measures designs. It also includes discussion of other relevant issues, including a brief review of the strengths and weaknesses of commonly available statistical software when applied to the analysis of repeated-measures data. PMID- 4042746 TI - Coping with aversive stimulation in the neonatal period: quiet sleep and plasma cortisol levels during recovery from circumcision. AB - Measures of behavioral state and plasma cortisol were obtained on 80 healthy, full-term, 2-3-day-old, male newborns who were scheduled to be circumcised. To establish baseline or precircumcision levels, the newborns were observed, and behavioral state was recorded for the half hour prior to circumcision. Blood was sampled via heelstick for plasma cortisol determination at the end of this observation period. The newborns were then circumcised and assigned randomly to one of 4 postcircumcision, blood-sampling time-point groups. The time points were 30, 90, 120, and 240 min following the beginning of circumcision. Behavioral state was observed during circumcision and for the half hour prior to taking the second blood sample. The results showed a return to baseline cortisol levels sometime prior to 240 min, with data from an additional group of 10 newborns indicating that the return occurred by 150 min. Behavioral distress during circumcision was associated with elevations in plasma cortisol at 30 and 90 min. Quiet sleep was correlated negatively with plasma cortisol prior to circumcision, and significant increases in quiet sleep followed circumcision, with the greatest increase corresponding to the period of most rapid reductions in cortisol. PMID- 4042747 TI - Use of the Bayley Scales to characterize abilities of premature infants. AB - The Bayley Scales of Infant Development were administered to 92 white, middle class infants, half of them premature and half full-term, at 1 year of age from term to determine whether this instrument is useful in characterizing the abilities of premature infants. Although both full-term and premature infants achieved mental and motor development scores within the average range, full-term infants attained significantly higher scores on both the Mental and Motor Scales. Both groups scored significantly lower on motor than mental functioning; however, the difference was significantly greater for premature infants. As a group, premature infants also evidenced greater variability in their performance on both the Mental and Motor Scales, and they showed greater intra-individual variability in performance of motor ability. Furthermore, premature infants were less likely to succeed on items testing eye-hand coordination, imitation, and vocalization. Preselected perinatal risk variables accounted for a significant amount of variance in both mental and motor ability of premature infants. PMID- 4042748 TI - Visual recognition memory: a predictor of later cognitive functioning in preterms. AB - A number of preterms who had participated in a study of visual recognition memory when they were 6 months of age were seen at older ages to assess the predictive validity of the early visual measures for cognitive outcome. The Bayley scales were administered at 6, 12, and 24 months, the Stanford-Binet at 34 and 40 months, and the WISC-R at 6 years. Novelty scores, which reflect the relative amount of time infants look at new compared to familiar stimuli, constituted the measure of infant visual processing. These scores, obtained by averaging over performance on the 3 or 4 problems administered at 6 months of age, were consistently and significantly related to cognitive measures from 24 months to 6 years, with correlations ranging from r = .53 to r = .66. Parental education, which was unrelated to novelty scores, bore a strong relationship to outcome beginning at 24 months. Although both measures contributed uniquely to the variance in cognitive outcome at 24 months and 6 years, visual novelty scores made a stronger contribution than did parental education. Neither 6- nor 12-month Bayley scores, nor various perinatal variables, were related to outcome. PMID- 4042749 TI - Infant temperament and subject loss in a habituation procedure. AB - It has been assumed that subject loss in habituation procedures is most likely due to random factors such as the behavioral state of the infant during testing. This study explored the possibility that infant temperament might contribute to subject loss. 114 infants at 3 age levels (11, 18, and 28 weeks) were rated by their mothers on a temperament questionnaire and then subjected to a habituation procedure. Analyses showed that female infants who were unable to complete the habituation task were reported as being more fussy and unadaptable. Female infants were less likely to complete at least part of the procedure than were male infants. The results suggest that subject loss in habituation studies may be the result of nonrandom individual difference factors and not just the result of temporary fluctuations in state. PMID- 4042750 TI - Development of the ability to use recall to guide action, as indicated by infants' performance on AB. AB - 25 infants were tested every 2 weeks on the AB Object Permanence Task devised by Piaget, from the age when they first reached for a hidden object until they were 12 months. The delay between hiding and retrieval necessary to produce the AB error increased continuously throughout this period at an average rate of 2 sec/month, from under 2 sec at 7 1/2 months to over 10 sec by 12 months. All children displayed the AB error repeatedly over the months of testing. Large between-children differences in delay needed for the AB error were found at each age. Girls tolerated longer delays than boys. The characteristic pattern to the AB error did not vary over age or sex. Range of delay producing the AB error in any child was small. Errors disappeared when delays were reduced by 2-3 sec, and reaching became random or severely perseverative when delays were increased 2-3 sec above the level producing AB error. AB provides an index of the ability to carry out an intention based on stored information despite a conflicting habitual tendency. PMID- 4042751 TI - Patterns of attachment in two- and three-year-olds in normal families and families with parental depression. AB - Patterns of attachment were examined in normal and depressed mothers. Mother's diagnosis (bipolar, major unipolar, or minor depression, or no psychiatric disorder), self-reported current mood states, and affective behavior in interaction with the child were considered. A modified version of Ainsworth and Wittig's Strange Situation was used to assess attachment. Insecure (A, C, and A/C patterns) attachments were more common among children of mothers with a major depression (bipolar or unipolar) than among children of mothers with minor depression or among children of normal mothers. Insecure attachment was more frequent in children of mothers with bipolar depression than in children of mothers with unipolar depression. A/C attachments were associated with histories of most severe depression in the mother. In families in which mothers were depressed, depression in the father did not increase the likelihood of anxious attachment between mother and child. However, if mothers with a major affective disorder were without a husband in the household, risk of an insecure mother child attachment was significantly increased. The mothers' expressed emotions (positive vs. negative) in interaction with their children in situations other than the Strange Situation, and independent of diagnosis, predicted patterns of attachment: mothers of insecurely attached children expressed more negative and less positive emotion. Mothers' self-reports of moods on the days they were observed were unrelated to attachment. Results are discussed in terms of the transmission of social and emotional disorders in relation to mothers' affective functioning. PMID- 4042753 TI - The development of error correction strategies in young children's manipulative play. AB - The focus of this study was the strategies used by young children between 18 and 42 months for correcting the errors they made as they attempted to nest a set of 5 seriated cups. In the process of combining the cups, the children committed numerous errors (such as putting a cup that was too large on a smaller cup), and they tried to correct the majority of those errors. Detailed examination of the children's correction attempts revealed that the strategies they used changed substantially with age, becoming increasingly more flexible and involving more extensive restructuring of the relations among the cups. Earlier correction attempts tended to focus on a single, nonfitting cup or on a single relation between 2 cups. Later-appearing strategies involved the coordination of relations involving several cups. The same trend toward increasing flexibility of thought and action also appeared in the procedures the children used to combine the cups. This study thus documents a finely graded series of cognitively significant changes in children's constructive activity during a period that has been poorly differentiated by cognitive developmental research. In so doing, it demonstrates the usefulness for problem-solving research of analyzing how subjects go about trying to rectify their own mistakes. PMID- 4042752 TI - How lower- and working-class youth become middle-class adults: the association between ego defense mechanisms and upward social mobility. AB - This is a report of social mobility in 278 inner-city men studied for 4 decades and over 3 generations. 63.3% of the men and 59.8% of their children were upwardly mobile. 8 variables captured 28% of the explained variance in upward social mobility: IQ, mother's education, mother's occupation, boyhood ego strength, and four ego defense mechanisms--intellectualization, dissociation, sublimation, and anticipation. Of the 8 variables, intellectualization--the capacity to isolate ideation from the associated affect--explained the most unique variance, especially over 3 generations. Childhood relations of subjects with parents and father's IQ exerted no discernible effect on children's upward social mobility. PMID- 4042754 TI - Young children's comprehension of montage. AB - 2 studies examined children's comprehension of brief stop-animation televised segments incorporating elements of cinematic montage such as pans, zooms, and cuts. Children reconstructed the action and dialogue in these segments using the same dolls and settings depicted. In Study 1, there was no effect of cinematic techniques on reconstruction performance of 3- and 5-year-olds as compared to control segments filmed without these techniques. The results challenged the assumption that the use of such techniques per se contributes to young children's poor comprehension of television shows. In Study 2, 12 new segments were produced in which comprehending the montage required inferences of character perspective, implied action sequences, spatial relationships, and simultaneity of different actions. Averaging across all segments, 62% of the 4-year-olds and 88% of the 7 year-olds demonstrated clear comprehension of the montage. Inferences concerning implied action sequences were easiest for both ages. Inferences of simultaneity were most difficult for 4-year-olds, whereas inferences of character perspective were most difficult for 7-year-olds. Preschool children are thus capable of understanding cinematic events conveyed through camera techniques and film editing, despite previous assertions to the contrary. This ability nevertheless substantially increases with age. PMID- 4042755 TI - [The influence of acidic conditions on polar exopolysaccharides which bind Rhizobium japonicum to soybean root hairs]. AB - The influence of acidic conditions on rhizobial exopolysaccharides (EPS) and their symbiotic association in host plants, were investigated. Light micrographs of soybean root hairs were taken with a Fahraeus' slide assembly after the inocubation of rhizobial bacteria; curled and swollen root hairs, and the typical shepherd's crook with an infection thread were observed. The colonizations of soybean root hairs by rhizobia were different under acidic and neutral conditions. For the Rhizobium japonicum strain USDA 136, and the indigenous acidic soil strain KR 23, morphologically distinct types of cells occurred in the acidic and neutral yeast-extract-mannitol broths. The surface structure of R. japonicum, as examined with the carbon replica and negative stain techniques, was rod shaped and polar flagellated only when the cells were incubated under neutral conditions. The materials which reacted with the ruthenium red positive reagent are in all likelihood an acidic EPS, and are believed to effect the adhesive properties of the cells. Bacterial polarity, which could be more readily observed under neutral conditions than under acidic conditions, was related to the distribution of EPS near one end of the bacteria. EPS was found to effect the initial step of polar attachment in the effective infection of host roots. By using DEAE-Sephacel ion exchange chromatography, the capsular polysaccharides from both strains of R. japonicum were also found to have different chemical components when observed in acidic and neutral cultures. PMID- 4042756 TI - Microbiological examination of foods sold via vending machines. AB - A total of 153 food specimens obtained from vending machines in Taipei city were subjects for the microbiological examination. Based on the standards for total microbial counts and total coliform counts established by the Department of Public Health, Republic of China, the unsatisfactory percentage of such counts for foods sold from vending machines were: 14% for carbonated beverages, 71% for non-carbonated beverages, 73% for ice cubes, and 100% for soft ice cream. Among the non-carbonic acid beverages examined, the unsatisfactory percentage for iced coffee, cocoa, chocolate milk, and fruit milk reached 90%. Escherichia coli and fecal streptococci each were found once. None of the pathogens causing food poisoning were found during the study. As for the sanitation control of vending machines examined, 66 to 74% percent were unsatisfactory. PMID- 4042757 TI - [Survey of helminthic infections and treatment of Taenia species infection among the aborigines in Chien-Shih District, Hsin-Chu County, northern Taiwan]. AB - Six hundred and sixteen out of 770 (80%) aborigines examined were found to be infected with intestinal helminthes. A total of 7 species of parasites were detected with the formalin-ether concentration technique. The infection rate of Ascaris lumbricoides was 77.1%, Trichuris trichiura 28.8%, Taenia sp. 18.4%, Enterobius vermicularis 1.6%, and there was one case each of hookworm, Hymenolepis nana and H. diminuta infections. Infection rate was slightly higher among females (81.3%) than males (78.9%). It was also higher in Yu-Feng (86.9%) than Shiu-Luan villages (75.5%). The incidence of helminthic parasites was found in all ages. 11-20 age-group was the highest (84.4%), followed by 1-10 (81.5%), 51 and more (80.6%), 41-50 (77%), 31-40 (76%), and 21-30 (72%). In general, the rate seems to be higher among the young and old. But, the rate of Taenia sp. was increased with the increase in age. Taenia sp. was found to be of considerable high prevalence. However, only 7 out of the 252 (2.7%) junior high school students were found infected in contrast to the 18.4% found in the villages. After atabrine treatment, 108 adult worms, 83 with and 25 without scolices were obtained from 54 of 72 treated cases. The number of expelled worms varied from 1 to 8, with an average of 2 worms per infected person. 29 (53.7%) aborigines expelled only one worm, and 25 (46.3%) cases expelled more than one worms. PMID- 4042758 TI - [Results of the surgical treatment of gallbladder carcinomas]. AB - A retrospective study of 44 patients with carcinoma of the gallbladder is presented. It is noticeable that although the prognosis for advanced carcinoma of the gallbladder is poor, that of the early stages (stage I-III) is relatively better. In no case diagnosis was made preoperatively. In 86% gallstones were found. There has been no valid staging for tumors of the gallbladder or any generally accepted standardized therapy. Attention is drawn to the possibility of improving the results of therapy at the early stages by extended radical operation and to the necessity for early operative treatment of gallstone disease. PMID- 4042760 TI - [Advantages of computerized tomography diagnosis in acetabular fractures]. AB - There is a comparison of conventional radiographs and computed tomography in 23 patients presenting acetabular fracture. Four patients were treated conservatively because of their CT-findings. The result was successful. Surgery took place in 19 patients. Intraoperative findings verified CT-diagnosis in all cases, while diagnosis with conventional radiographs in 3 projections had to be corrected in 8 of 19 cases. Advantages of CT in acetabular fracture: 1. always manageable, 2. correct topography of fracture, 3. discovery of small especially intraarticular bone fragments, 4. judgement of congruity of the joint, 5. clear decision of management. 6. definite surgical approach. In conclusion, the CT scanning of acetabular fractures is preferable for correct classification as opposed to conventional radiographs; if only plain X-ray films are available CT scanning is to be required. PMID- 4042759 TI - [Femoropedal bypass: a step forward in peripheral bypass surgery?]. AB - Femoropopliteal and femorocrural bypasses are standardized procedures. There is given a patency rate of 70-90% after a period of 5 years according to the progress of the disease and to the used graft material. Bypassing the lower limb in AOD (stage III and IV by Fontaine) it is possible to implant a femoropedal bypass. In our patients we had a patency rate of 81.3% during a follow-up time of 13 months. An av-shunt nearby the distal anastomosis seems to be important. PMID- 4042761 TI - [Biomechanical analysis of the medullary bone nail and its locking]. AB - By mechanical definition an intramedullary nail is not a nail but rather a bendable feather, subject to longitudinal tension and to a lesser degree to transverse pressure. Reaming the medullary canal is necessary for centralization of the nail as well as to increase the area of contact with the bone. However, this procedure is detrimental to the bone metabolism and reduces its elasticity against torsional forces. The dynamic locking nail-system is more biologic than conventional nailing and it reduces rotatory instability with the help of additional components, such as transverse screws. Only static locking allows true static weight bearing with crutches, but not dynamic mobilisation. Nails with conventional strength and in leaf of trefoil formation are superior to other designs. However, an improved angle in the proximal locking is suggested, as this would allow for a three to four times greater weight bearing. PMID- 4042762 TI - [Sacroiliac distorsion or subluxation--a medically established concept? X-ray diagnosis--bone scintigraphy]. AB - 50 patients with complaints in the region of the sacroiliacal joints and the hip, but negative radiographs following injury to the pelvis were investigated by bone scan. Scintigraphic diagnosis always showed involvement of the pelvis ring other than the apparent fractures. Together with the clinical symptoms scintigraphic findings are interpreted as sacroiliacal strain or subluxation. Additional injuries to the acetabulum and to the lumbosacral joints may be present. The patients' complaints are explained, the injuries are localized and documented. PMID- 4042763 TI - [Differential surgical indications in benign tumors of Vater's ampulla]. PMID- 4042764 TI - [Malignant melanoma of the gallbladder]. PMID- 4042765 TI - [Perforation by a foreign body in esophagus duplication in an infant]. PMID- 4042766 TI - [A new "nontraumatic" towel forceps]. PMID- 4042767 TI - [Chemotherapy of the recurrence of tumors of the gastrointestinal system]. PMID- 4042768 TI - [Therapy of recurrent colorectal cancers]. AB - Colorectal cancers treated for cure by operative means show tumour recurrences and metastases in about 20% of the patients. Of these colon or rectal cancers 75 and 90% respectively can be only operated for palliation. These patients have a better prognosis than those operated primarily for palliation. 25% of the cases especially with suture line recurrences can be operated upon radically enough and exhibit a total five year survival rate of 50%. PMID- 4042769 TI - [Significance of hemodynamic sequelae of aortic ligation in infrarenal aneurysms of the abdominal aorta]. AB - The operative mortality in abdominal aortic aneurysm repair is in large part attributable to a high incidence of myocardial infarction. This is a result of cardiovascular instability during aortic cross-clamping and declamping in patients with coexistent coronary artery disease. Therefore cardiodynamics (pulmonary arterial wedge pressure, PAWP; cardiac index, CJ) were studied in 31 patients during abdominal aortic aneurysm surgery. 12 patients (control) with a PAWP mean of 8 mmHg preoperatively showed impaired cardiac function after declamping and a significant fall in arterial pressure. 19 patients were volume loaded to a PAWP greater than 12 mmHg and the cyclo-oxygenase inhibitor Aspirin was given preoperatively. This resulted in improved cardiac performance with no fall in arterial pressure after declamping. Optimal volume loading and cyclo oxygenase inhibition have the ability to prevent adverse hemodynamic responses to aortic clamping and declamping. Maintenance of optimal cardiac performance will reduce cardiovascular complications and postoperative mortality in abdominal aortic aneurysm repair. PMID- 4042770 TI - Transition from somatic to meiotic pairing and progressional changes of the synaptonemal complex in spermatocytes of Aedes aegypti. AB - Aedes aegypti spermatocytes were reconstructed from electron micrographs. The species has tight somatic pairing of the chromosomes, and there are therefore no classical leptotene and zygotene stages, but rather a gradual transition from somatic pairing to meiotic pairing (= pachytene). The term "prepachytene" has been used for the transitory stage. The first visible sign of impending meiosis was a reorganization of the chromatin, which resulted in the formation of spaces (synaptic spaces) in the chromatin, about the width of the synaptonemal complexes (SCs). Diffuse material, possibly precursor material for the SC, was present in the spaces. Later short pieces of complex were formed throughout the nucleus. Late prepachytene, pachytene, and diplotene complexes were reconstructed. Each chromosome occupied a separate region of the nucleus. The complexes became progressively shorter from prepachytene (maximum complement length 289 micron) to diplotene (175 micron). The thickness of the SCs increased from prepachytene to pachytene and probably decreased again during diplotene. At the beginning of diplotene the lateral elements (LEs) separated, and the single LEs became two to three times thicker than the LEs of the SC. The centromeres were at all stages attached to the nuclear membrane, whereas the telomeres were free in the nucleoplasm during pachytene and diplotene. A heterochromatic marker was present on chromosome 1 near the sex determining locus, and a diffuse marker on chromosome 3 near the nucleolus organizer region. After breakdown of the complexes, polycomplexes were present in the nucleus. PMID- 4042772 TI - Microtubules, chromosome movement, and reorientation after chromosomes are detached from the spindle by micromanipulation. AB - The relationship between chromosome movement and microtubules was explored by combining micromanipulation of living grasshopper spermatocytes with electron microscopy. We detached chromosomes from the spindle and placed them far out in the cytoplasm. Soon, the chromosomes began to move back toward the spindle and the cells were fixed at a chosen moment. The microtubules seen in three dimensional reconstructions were correlated with the chromosome movement just prior to fixation. Before movement began, detached chromosomes had no kinetochore microtubules or a single one at most. Renewed movement was always accompanied by the reappearance of kinetochore microtubules; a single kinetochore microtubule appeared to suffice. Chromosome movements and kinetochore microtubule arrangements were unusual after reattachment, but their relationship was not: poleward forces, parallel to the kinetochore microtubule axis (as in normal anaphase), would explain the movement, however odd. The initial arrangement of kinetochore microtubules would have led to aberrant chromosome distribution if it persisted, but instead, reorientation to the appropriate arrangement always followed. Observations on living cells permitted us to place in sequence the kinetochore microtubule arrangements seen in fixed cells, revealing the microtubule transformations during reorientation. From the sequence of events we conclude that chromosome movement can cause reorientation to begin and that in the changes which follow, an unstable attachment of kinetochore microtubules to the spindle plays a major role. PMID- 4042773 TI - [Peak expiratory flow (PEF) in normal subjects and patients with bronchial asthma]. PMID- 4042771 TI - Interactions of nuclear proteins with DNA, during sperm differentiation in the ram. AB - Ram spermatid nuclei and caput epididymal sperm nuclei were prepared and treated with DTT under conditions avoiding proteolysis. Whole-mount preparations for the electron microscope were made in the presence or absence of the detergent Joy. The chromatin of the less mature, non-round spermatid nuclei displayed a nucleosomal organization that gradually disappeared at the time the histones leave the nuclei (elongating spermatids). Digestion with micrococcal nuclease suggests that polynucleosome arrays are scarcer and more accessible to nuclease in the elongating than in the round nuclei, with increasing amounts of DNA becoming devoid of nucleosomes. In the protamine-containing nuclei (elongated spermatids), only smooth filaments were observed, which formed thick fibers by parallel aggregation. The change from a nucleosomal organization to bundles of smooth filaments appeared to result from a complex process involving the transitory presence of conspicuous "knobby fibers" that suggest a periodicity in the organization of the spermatidal proteins along the DNA molecules. X-ray diffraction patterns obtained with protamine-containing spermatid nuclei and with sperm nuclei confirm that the DNA is arranged in smoothly bent bundles of parallel molecules. No higher-order reflections that might correspond to nucleosome structures were detected in the 30-200 A region. PMID- 4042775 TI - [Evaluation of measuring the diameter of the common pulmonary artery by two dimensional ultrasonic cardiography in the diagnosis of chronic cor pulmonale]. PMID- 4042774 TI - [Extrinsic allergic alveolitis: report of 8 cases with pigeon fancier's lung]. PMID- 4042776 TI - [Comparative study of the direct measurement and echocardiographic observation of pulmonary pressure in healthy adults and patients with the chronic obstructive pulmonary diseases at high altitude]. PMID- 4042777 TI - [Body-plethysmography and its constants]. PMID- 4042778 TI - [Diagnosis and treatment of atelectasis with fiberobronchoscopy: analysis of 374 cases]. PMID- 4042779 TI - [Radiographic-pathologic correlative study of 311 cases of pulmonary tuberculosis]. PMID- 4042780 TI - [Survey of the tuberculosis initiative case-finding method]. PMID- 4042781 TI - [Modes of case-finding of tuberculous patients in rural areas]. PMID- 4042782 TI - Evaluation of a new blood cell counter with sheath flow system. AB - A blood cell counter with a sheath flow system has been developed to eliminate the drawback of the Coulter type blood cell counter, namely, signal distortion caused by the cells passing through the electric aperture gate. With the new system, signal distortion was low and a near-normal distribution curve for erythrocytes and resin particles was obtained. The counter has a computer program for determining the red cell distribution width, which represents an actual size difference at 20% of the relative frequency of the distribution curve. This is independent of mean cell volume, and is considered to be of clinical importance. We examined the values in 2,300 healthy subjects and patients with various hematological disorders. PMID- 4042783 TI - Analysis of the expression of cloned HLA class I genes in mouse transfected L cells by quantitative flow cytometry. AB - By using a calibrated cell sorter and monoclonal antibodies conjugated to fluorochromes, a quantitative analysis of the levels of expression of HLA class I molecules at the surface of cloned murine L cells transfected with purified A3, B7, or CW3 genes was performed and compared with radioimmunoassay data. We selected clones of heterogeneous levels of HLA class I expression, which were shown to remain constant over a period of 4 mo in absence of HAT selection and not to be correlated to the DNA copy number of the corresponding integrated gene. PMID- 4042784 TI - Cell kinetic effects of incorporated 3H-thymidine on proliferating human lymphocytes: flow cytometric analysis using the DNA/nuclear protein method. AB - Phytohemagglutinin-stimulated human peripheral blood lymphocytes incorporating high concentrations of 3H-thymidine accumulate in G2 and show a consequent reduction in the number of cells entering M (division delay). The simultaneous flow cytometric analysis of DNA content (propidium iodide fluorescence) and nuclear protein content (fluorescein isothiocyanate fluorescence) allows for the accurate quantitation of these events; G2 and M are separated in the bivariate distributions. A good correlation was observed between mitotic indices, quantitated by manually counting mitotic cells, and integration of the M area in DNA/nuclear protein histograms. Moreover, significant differences in G2 nuclear protein levels were found between untreated and 3H-thymidine-treated lymphocytes. In order to characterize this effect, G2 was empirically divided into low nuclear protein (G2A) and high nuclear protein (G2B) compartments. 3H-thymidine caused an initial accumulation of lymphocytes in G2A, followed within 3-6 h by a gradual movement of some cells into G2B, with a subsequent accumulation of cells in G2B. The results suggest that the distribution of cells in G2 (G2A and G2B), the average nuclear protein content of G2B cells, and the proportion of cells in M are parameters that when used in combination provide a unique description of radiobiological effects. PMID- 4042785 TI - Flow cytometry of human colorectal tumors: nuclear isolation by detergent technique. AB - A simple one-step technique for detergent isolation and DNA staining of nuclei from mouse colon and from human colorectal tumors was investigated. Nuclear yield increased with treatment time, up to 24 h. There were only minor differences when detergent concentrations from 0 to 0.6% were used. The lowest (0.03%) concentration was most effective. No loss of nuclei was effected by cell lysis and no selectivity was observed for isolation of certain cell-cycle phases or ploidy classes from heterogeneous tumors. The nuclei were stable in the stain detergent solution for 24 h, but lymphocytes were sensitive to the possible proteolytic activity of one of the two commercial RNase preparations. Of the total number of parenchymal nuclei in mouse liver, as estimated by a stereological method, approximately 60% were isolated by the procedure (approximately 0.9 X 10(8) nuclei/g tissue). From mouse colon the average nuclear yield was 1.8 X 10(8)/g, and from human colorectal tumors 0.9 X 10(8)/g (ranges 0.3-1.9 X 10(8]. Microscopic examination of undissolved tissue fragments from the preparation of tumors and mouse colon showed a high selectivity for isolation of epithelial and neoplastic nuclei, leaving the stroma with its nuclei almost intact. PMID- 4042787 TI - DNA image cytometry on machine-selected breast cancer cells and a comparison between flow cytometry and scanning cytophotometry. AB - A DNA image cytometry method, implemented on the LEYTAS image processing system, has been applied to acriflavine-Feulgen-stained breast cancer cytology specimens. An essential feature of the LEYTAS image cytometry method (LCM) is the automated selection of single nuclei according to predetermined specifications. Visual interaction has been used to reject remaining artefacts like overlapping nuclei. DNA profiles obtained with LCM have been compared with DNA profiles obtained by scanning cytophotometry (SCM) or flow cytometry (FCM). The resolution of DNA profiles obtained with LCM is similar to that from SCM but lower than that from FCM. However, a high correlation is found for the DNA indices measured with LCM and FCM (r = 0.97). The LCM profiles of aneuploid tumours generally showed lower accessory diploid fractions than FCM profiles due to the automated rejection of leukocyte nuclei. Also, LCM profiles frequently showed the presence of minor subpopulations of highly aneuploid/polyploid tumour cells that could not be identified by FCM. Therefore, LCM appears to be supplementary to FCM for studying tumour cell stemline heterogeneity. PMID- 4042786 TI - Flow cytometric analysis of head and neck carcinoma DNA index and S-fraction from paraffin-embedded sections: comparison with malignancy grading. AB - Archival, paraffin-embedded, pathology specimens representing pretreatment tissue biopsies from 73 patients with epidermoid carcinoma of the head and neck were analyzed for DNA Index and %S-phase cells by flow cytometry and were scored for quantitative histomorphology. The DNA fluorescence/light scatter size patterns derived from paraffin-embedded specimens were shown to be essentially the same as those from mechanically disaggregated, ethanol-fixed cells obtained from the same tissue specimen. Patterns ranged from lymphocyte-like to highly abnormal DNA Index cytokinetic patterns. The DNA Index values ranged from 0.70 to 3.50 (median 1.42), with an aneuploidy frequency of 63/73 (86%). DNA distribution %S ranged from 4% to 45% (mean 19), with the microscopic malignancy grading showing broad heterogeneity (mean 2.1, range 1.0-3.0, where 1.0-1.7 = well differentiated, 1.8 2.3 = moderately differentiated, 2.4-3.0 = poorly differentiated). Cross comparison of these data showed that (1) the tumor %S was dependent on DNA Index (higher %S at higher ploidy), (2) low to high malignancy tumors were randomly distributed between diploid/near diploid tumors and high-degree DNA abnormality tumors, and (3) proliferative activity values broadly overlapped between low to high malignancy scored tumors. However, those carcinomas characterized by high DNA Index (greater than or equal to 1.50) and high %S-phase fractions (greater than or equal to 20) had a five fold higher incidence of high-degree malignancy, invasive tumors than diploid/near diploid (%S less than or equal to 19) tumors. PMID- 4042788 TI - Spot-blot analysis of sorted chromosomes assigns a fructose intolerance disease locus to chromosome 9. AB - The aldolase B gene was mapped to chromosome 9 using a rapid gene mapping system. This system uses a dual-laser sorter to identify and separate metaphase human chromosomes stained with either DIPI-chromomycin or Hoechst-chromomycin. Chromosome panels were constructed from a normal cell line by sorting 22 chromosome fractions directly onto nitrocellulose filters. Twelve labeled gene probes hybridized to the sorted chromosomal DNA fractions predicted by previous chromosome assignments. Eighteen newly cloned genes have been mapped using the same protocol. PMID- 4042789 TI - Droplet sorting of large particles. AB - The systematics of droplet formation conditions for orifices with diameters up to 200 micron are described. Sorting recovery experiments indicate that particles up to 44 micron in diameter can be recovered by charged droplet deflection of two drops with at least 75% recovery. By reducing the jet velocity, a deflection of greater than 1 cm was obtained for all droplet sizes. PMID- 4042790 TI - The relationship between mean channel selection and the calculated coefficient of variation. AB - Calculated coefficients of variation (CV) taken from the quotient of the standard deviation (S.D.) and the mean value of measured distributions are often used as an indicator of system performance in linear flow cytometry (FCM). The ability of the calculated CV to estimate the true CV of the underlying experiment before grouping (channelization) is dependent on the relationship between the width of the data channels and the magnitude of the S.D. of the measured distribution. When the channel width is equal to the S.D. of a distribution, the calculated CV is approximately 20% larger than the true CV of an experiment. By the time the S.D. is only one-half of a channel width, the calculated CV is unreliable. When the distribution S.D. is narrower than a channel's width, small changes in the distribution mean value will cause large variations in the calculated CV. As the true CV decreases, the calculation must be made with higher mean channel values. This dependence of calculated CV accuracy upon the relationship between S.D. and channel width places limitations upon mean channel selection that must be considered when using CV calculations for evaluating system performance, especially when looking for small improvements during optical alignment procedures. When an instrument is assumed to have a constant CV and the data are collected linearly, it is possible to improve the CV estimation accuracy by placing distributions in higher-numbered channels.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4042791 TI - A fast cell sampler for flow cytometry. AB - A simple device has been developed for delivering samples into a flow cytometer. Designed with economy, simplicity, and flexibility in mind, this device, having only one moving part, can be used for sample volumes as small as 20 microliter, for virtually any form of cell sample container, and for a wide range of cell concentrations. It consists essentially of a lever-operated disc valve that allows the cell sample to be loaded into a loop of tubing and then to be injected into the cytometer nozzle under pressure from a saline source. The sampler has lifted the maximum analytical throughput of a FACS II cell sorter to better than 120 samples per hour. PMID- 4042792 TI - Pharmacokinetics of vitamin K1 in low-birth-weight neonates. AB - The pharmacokinetics of vitamin K1 was studied in 21 newborn infants. 11 neonates had received no parenteral loading dose prior to the study (group I), while 10 had been injected 5-10 mg vitamin K1 at birth (group II). At postnatal age 2-9 h, 1 mg of vitamin K1 was injected intravenously, and small samples of blood (less than or equal to 500 microliter) were collected at different times during 6 h. Serum vitamin K1 and its epoxide were assayed by high-performance liquid chromatography (HPLC). In both groups, the disappearance curve showed two exponential components: a fast distribution component during the 1st h and a slower elimination component during the next 5 h. In group I, the plasma half life of the first component was between 18 and 52 min (median 23 min), and the half-life of the second was between 67 and 179 min (median 109 min). Both half lives were significantly higher in group II. The volumes of distribution were suggestive of distribution into plasma during the first phase and roughly into the extracellular water for the second component. Epoxide was detected in most patients 15 min after vitamin K1 injection, and after 3 h its concentration was higher than the concentration of vitamin K1. These data suggest that the kinetics of vitamin K1 in neonates is not very different from that in adults. The newborn infant is able to oxidize vitamin K1, a phenomenon in keeping with the gamma carboxylation of glutamic acid. PMID- 4042793 TI - Influence of continuous gastric suction on theophylline clearance in a newborn. PMID- 4042794 TI - Hemodynamic and acid-base effects of promazine on unanesthetized pregnant sheep and fetus. AB - Although promazine has been used in obstetrics for over 20 years, its effects upon hemodynamic and acid-base conditions of steady-state pregnant sheep and fetus has not been sufficiently investigated. To study these effects, 10 experiments were performed in 5 ewes and their fetuses. Promazine (1 mg/kg/4 min) was administered intravenously to the ewes. Significant maternal changes included: reduction in hemoglobin from 9.1 +/- 0.43 to 8.4 +/- 0.43 g/100 ml at 120 min, O2 content from 12.1 +/- 0.61 to 10.8 +/- 0.59 vol% at 90 min, O2 saturation from 9.7 +/- 2.58 to 95.4 +/- 2.80% at 15 min, and blood pressure from 86.1 +/- 4.94 to 74.1 +/- 2.55 mm Hg at 45 min. The heart rate increased from 84 +/- 2.64 to 100 +/- 5.03 beats/min at 120 min. The uterine blood flow remained unchanged. The fetus developed mild metabolic acidosis as manifested by the reduction in pH from 7.375 +/- 0.008 to 7.35 +/- 0.005 at 45 min. No other fetal hemodynamic changes were observed. The significance of these findings is discussed. PMID- 4042795 TI - Retinopathy in young-onset diabetic patients. AB - The relative importance of duration of diabetes before and after 13 yr of age as a risk factor for retinopathy was investigated using data from 200 persons who were younger than 26 yr of age. These persons were identified in a population based study of diabetic retinopathy in southern Wisconsin in 1980-1982. Retinopathy was found in 9% of persons who were younger than 13 yr and in 34% of persons who were 13 yr or older and had been diagnosed at or after 13 yr. Presence of retinopathy was more strongly associated with the duration of diabetes after 13 yr of age than before it. PMID- 4042796 TI - Incidence of diabetic retinopathy and blindness: a population-based study in Rochester, Minnesota. AB - Among the 1135 Rochester residents discovered to have diabetes in the period 1945 69, the prevalence of retinopathy was 2.6% at the time of initial diagnosis. Among those free of retinopathy at diagnosis of diabetes, the subsequent incidence of any retinopathy was 17.4 per 1000 person-years and for proliferative retinopathy alone was 1.6 per 1000 person-years, based on 12,000 person-years of follow-up. The incidence rate of retinopathy was almost three times greater among residents with insulin-dependent (IDDM) than with non-insulin-dependent diabetes (NIDDM); however, the actual number of retinopathy cases was over four times greater among the more numerous residents with NIDDM. By 20 yr after diagnosis of diabetes, the cumulative incidence of retinopathy approached 70% among IDDM subjects and was 30% and 36%, respectively, among the obese and nonobese NIDDM residents. The epidemiologic patterns for proliferative retinopathy were qualitatively similar to those for nonproliferative retinopathy. The risk of blindness was greater among those with proliferative than with nonproliferative retinopathy but was substantial even for those without retinopathy. Most blindness was caused by factors other than isolated diabetic retinopathy. PMID- 4042797 TI - The prevalence of retinopathy is similar in diabetes mellitus secondary to chronic pancreatitis with or without pancreatectomy and in idiopathic diabetes mellitus. AB - In a retrospective study, we compared the prevalence of retinopathy in two groups of 88 diabetic patients (84 men, 4 women) with either diabetes mellitus secondary to chronic pancreatitis (CP-DM group) or idiopathic diabetes mellitus (I-DM group). The patients of these two groups were pair-matched according to age (48.7 +/- 1.1 versus 48.8 +/- 1.0 yr in CP-DM and I-DM groups, respectively; mean +/- SEM), sex, duration of diabetes (7.96 +/- 0.56 versus 8.08 +/- 0.8 yr) and therapy (80 on insulin and 8 on oral hypoglycemic agents in each group). Retinopathy was assessed by bilateral ophthalmoscopic examination of the fundus after pupillary dilation in all 176 patients and by fluorescein angiography in 47 patients with CP-DM and 35 patients with I-DM. Forty-one percent of patients in the CP-DM group and 45.5% of patients in the I-DM group had diabetic retinopathy (P greater than 0.5). In each group, patients with retinopathy were older than patients without retinopathy (51.6 +/- 1.3 versus 46.7 +/- 1.8 yr in the CP-DM group, P less than 0.01, and 52.1 +/- 1.5 versus 46.0 +/- 1.2 yr in the ID-M group, P less than 0.01). They had diabetes of longer duration (10.9 +/- 1.0 versus 5.9 +/- 0.6 yr in the CP-DM group, P less than 0.001, and 10.5 +/- 1.0 versus 6.0 +/- 0.6 yr in the ID-M group, P less than 0.001). The prevalence of retinopathy increased parallel to the duration of diabetes in a similar way in both groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4042798 TI - Quantification of early subclinical limited joint mobility in diabetes mellitus. AB - Limited joint mobility (LJM) has been described in juvenile diabetic patients by Rosenbloom et al.; similar abnormalities are also present in adult diabetes. This modification may be associated with a high risk of microvascular complications. We tested the use of a goniometer in measuring subclinical joint limitation in 50 adult diabetic patients without overt, i.e., clinically evident, LJM as described by these authors. This diabetic population was compared with 118 nondiabetic adult controls. We found significant changes in hand mobility between the two groups for wrist flexion and extension of the 3rd and 5th fingers (P less than 0.001). Age was correlated to wrist flexion, wrist extension, and proximal interphalangeal flexion of the little finger. Wrist extension correlated with duration of diabetes (r = -0.37, P less than 0.01). Heavy manual activities significantly limited all motions except wrist and 5th finger metacarpophalangeal flexion. Early systematic examination by goniometry may prove to be a sensitive, quantitative, and inexpensive way of detecting joint stiffness at an early stage. PMID- 4042799 TI - Neonatal mortality in infants of diabetic mothers. AB - To assess the effects of an educational program emphasizing detection and tight control of maternal glucose levels during pregnancy, the management and outcome of all pregnancies complicated by diabetes mellitus delivered at a county hospital during two time periods, 1978-1980 and 1981-1983, are compared. The prevalence of diabetes during pregnancy was 1.4% between 1978 and 1980 and 2.6% between 1981 and 1983 (P less than 0.01). The perinatal death rate decreased for infants of diabetic mothers from 100 per thousand deliveries in 1978-1980 to 32 per thousand in 1981-1983 (P less than 0.02). The perinatal death rate for infants of mothers with gestational diabetes was nearly the same as the perinatal death rate for all neonates born in the state in 1981-1983. Congenital anomalies followed by stillbirths were the most frequent causes of perinatal death. PMID- 4042800 TI - Prospective evaluation of HDL cholesterol changes after diet and physical conditioning programs for patients with type II diabetes mellitus. AB - High-density lipoprotein (HDL) cholesterol is known to be low in patients with diabetes mellitus. Low HDL levels are correlated with premature cardiovascular mortality in several major epidemiologic studies and many investigators believe increases in HDL cholesterol may reduce the risk of coronary heart disease. We evaluated dietary and exercise interventions in relation to HDL cholesterol in patients with type II diabetes mellitus. Sixty-five volunteers were randomly assigned to one of four experimental conditions: diet, exercise, diet plus exercise, or education control. Three months after entering the program, those exposed to the dietary intervention had significant increases in HDL cholesterol. HDL increases for the other two treatment groups did not differ significantly from the education control. PMID- 4042801 TI - Pancreatic polypeptide: a marker for lean non-insulin-dependent diabetes mellitus? AB - Both basal and postprandial pancreatic polypeptide (PP) concentrations were exaggerated twofold in lean NIDDM patients, whereas they were normal in lean IDDM and obese NIDDM patients who were hyperglycemic as a result of partial insulin withdrawal. Insulin infusion from an artificial endocrine pancreas, which resulted in fasting euglycemia and near-normoglycemia postprandially, had no effect on PP responses in any of the diabetic patients. No postprandial PP responses were observed in totally pancreatectomized (TPX) patients. Excessive basal and postprandial concentrations of PP in diabetes appear to be related to both leanness and residual beta cell function and, therefore, potential markers for lean NIDDM. PMID- 4042802 TI - Self-monitoring of blood glucose: how accurate are children with diabetes at reading chemstrip bG? AB - Accuracy of self-monitoring of blood glucose (SMBG) using Chemstrip bG (Bio Dynamics, Indianapolis, Indiana) was studied in 90 randomly selected children with insulin-dependent diabetes mellitus (IDDM). For 28 children (mean age 8.3 +/ 3.6 yr) a parent routinely read the Chemstrip at home. The remaining 62 children (mean age 13.7 +/- 2.8 yr) read the Chemstrip themselves. Each child or parent analyzed 20 capillary blood samples using Chemstrips and answered a questionnaire on SMBG. The accuracy of SMBG of the group was high (mean correlation coefficient = 0.89 +/- 0.05), but consistency of measurement was variable (mean standard deviation = 1.90 +/- 0.57) and there was a general tendency to underread Chemstrips (mean y-intercept = 1.05 +/- 1.48; mean slope = 0.80 +/- 0.17). For each subject, 0-65% (mean of 34%) of readings were within 10% of the laboratory measurement, and 17-100% (mean 68%) within 20%. These results indicate that most subjects were fairly accurate in reading Chemstrips; however, analysis of accuracy is useful in identifying individuals who are inaccurate or inconsistent in SMBG. Continuing supervision of SMBG is necessary in children with IDDM. PMID- 4042803 TI - High prevalence of maturity-onset diabetes of the young (MODY) among Indians. AB - This article describes the high prevalence of maturity-onset diabetes in the young (MODY) in an Indian clinic population of diabetic patients. MODY appears to be more common among Indians than among Caucasians. Only 27% of MODY patients had definite autosomal-dominant inheritance. In 73% the mode of inheritance was not definite. Microvascular complications were common and macrovascular complications rare. The high prevalence of MODY in this diabetes clinic might suggest an ethnic variation in diabetes. PMID- 4042804 TI - The effect of blood glucose concentration on labile A1c in diabetic patients. AB - We investigated the magnitude of labile A1c in total A1c measured rapidly by a chromatographic method, and whether or not there was an effect of blood glucose before and after a meal on labile A1c in 94 type I and 178 type II diabetic subjects. There were strong correlations between serum glucose and labile A1c both in type I (r = 0.76, P less than 0.001) and in type II diabetic subjects (r = 0.72, P less than 0.001). These relationships did not change before and after the meal. As labile A1c increased in proportion to blood glucose, it could be calculated from the blood glucose level in simultaneous blood samples. In type I diabetic subjects, below the 100-mg/dl glucose level labile a was negligible, and above 100 mg/dl about 0.35% labile A1c was increased every 50-mg/dl increment of glucose. In type II diabetic subjects, below a 150-mg/dl glucose level labile A1c was in the normal range (0.58 +/- 0.15%), and above the 150-mg/dl glucose level every 50-mg/dl increment of glucose increased about 0.3% of labile A1c. If this process is used, stable A1c can be calculated easily from total A1c and coincident serum glucose, even though labile A1c is not removed by incubation. PMID- 4042805 TI - Glucose tolerance in granuloma annulare. AB - Granuloma annulare (GA) may be associated with glucose intolerance. Twenty-one patients with GA were evaluated. Four patients were found to have frank diabetes mellitus and 2 were excluded from the data analysis because of obesity. The remaining patients and 14 age- and weight-matched controls had oral and intravenous glucose tolerance tests (GTT). During the oral GTT the fasting plasma glucose, the 2-h plasma glucose, the area of the glucose curve, the 1-h serum insulin, and the area of the insulin curve were all significantly greater in the GA patients than in the controls. During the intravenous GTT the immediately releasable insulin pool was intact, while the fasting plasma glucose and the area of the glucose curve were greater in the GA patients than in the controls. The data taken together suggest that glucose tolerance may be reduced in GA and that insulin resistance may exist. PMID- 4042806 TI - Diabetic nephropathy and proliferative retinopathy with normal glucose tolerance. AB - A 61-yr-old man presented with the nephrotic syndrome and normal oral glucose tolerance. Renal biopsy showed the nodular (Kimmelstiel-Wilson) and diffuse glomerulosclerosis lesions characteristic of diabetes. Direct ophthalmoscopy and fluorescein angiography demonstrated a picture of advanced proliferative diabetic retinopathy. The patient had no history of diabetes mellitus and upon testing had normal glucose values in response to an oral glucose tolerance test. Insulin response to an intravenous glucose tolerance test was abnormally low. It is concluded that the nodular glomerulosclerosis lesions and proliferative retinopathy, thought to be specific for diabetes mellitus, may present in the absence of either overt clinical diabetes or impaired glucose tolerance. PMID- 4042807 TI - Commentary on the National Standards for Diabetes Patient Education Programs. PMID- 4042808 TI - Effect of stress on blood glucose in IDDM. PMID- 4042810 TI - "Locked in" syndrome following prolonged hypoglycemia. PMID- 4042809 TI - Rectal glucose administration cannot be used to treat hypoglycemia. PMID- 4042811 TI - Molecular cloning of mouse mammary gland kappa-casein: comparison with rat kappa casein and rat and human gamma-fibrinogen. AB - A cDNA clone for kappa-casein mRNA from the lactating mouse mammary gland was isolated and its nucleotide sequence determined. Analysis of the deduced amino acid sequence revealed a precursor protein with a 21-amino-acid signal sequence and a mature protein of 160 amino acids, the mature mouse protein being 3 amino acids longer than the rat kappa-casein. Northern blot analysis of the lactating rat and mouse mammary gland showed a specific mRNA for rat kappa-casein and two distinct mRNAs for mouse kappa-casein. This result is explained by the presence of two putative polyadenylation sites in mouse kappa-casein cDNA, whereas rat kappa-casein cDNA has only one polyadenylation site. Comparison of the nucleotide sequence and of the deduced amino acid sequence of kappa-casein from mouse with that of the rat showed 85% homology between the two sequences. However, when amino acid sequences of kappa-casein from rat and mouse were compared with ovine kappa-casein, only a 45% homology was observed. Amino acid sequences of kappa casein from rat, mouse, and sheep were 36.53% homologous with rat and human gamma fibrinogen. The extent of homology was similar (32%) when nucleotide sequences of corresponding cDNAs were compared. The stretches of homology existing at different regions between the two proteins were more confined toward the amino terminal half of gamma-fibrinogen. However, when nucleotide sequences were compared, mouse kappa-casein cDNA showed homology only with the second half of the rat gamma-fibrinogen cDNA, i.e., between nucleotides 661-1135. The homology with the human gamma-fibrinogen cDNA spanned over two regions, one between nucleotides 1-328 and the second between nucleotides 591-726.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4042812 TI - Cloning and sequencing of a human 18S ribosomal RNA gene. AB - A clone containing an 18S ribosomal RNA (rRNA) gene has been isolated from a human genomic library constructed in lambda Charon 4A. This gene was sequenced and found to be 1868 bp long. The sequence divergencies in the human 18S rRNA gene and the previously sequenced mouse and rat genes are found in one G + C-rich region of 110 bp located in the 5' domain of the molecule. Except for this variable region, extensive homology exists among these three mammalian genes. Overall, the human 18S rRNA gene is 98.8% homologous with those of rat and mouse. PMID- 4042813 TI - Thyroid hormone regulation of thyrotropin alpha- and beta-subunit gene transcription. AB - We studied the effect of thyroid hormone on the transcription of the genes for the alpha- and beta-subunits of thyrotropin (TSH) in thyrotropic tumors (IAK 109D and 109F) carried in hypothyroid mice. Gene transcription was measured in isolated nuclei by allowing completion of RNA chains initiated in vivo in the presence of [alpha-32P]UTP and by hybridization of labeled RNA transcripts to filter-bound plasmids containing alpha or TSH-beta cDNA sequences. Treatment of animals carrying tumor IAK 109D with 3,5,3'-triiodo-L-thyronine (T3) (5 micrograms/100 g body weight) for 2 hr reduced TSH-beta gene transcription to less than 10% of control levels, whereas alpha RNA synthesis was reduced to 59% of control. The inhibition of TSH-beta gene activity was maintained after 6 hr of T3 treatment, whereas alpha gene transcription rose slightly to 77% of control. The tumor content of alpha and TSH-beta mRNA, determined by dot blot hybridization with 32P-labeled plasmid probes containing alpha or TSH-beta cDNAs, was unchanged after 2 hr of T3 treatment, and each was reduced by approximately 25% at 6 hr. These untreated tumors contained approximately equal amounts of alpha and TSH-beta mRNA. However, the basal rate of TSH-beta gene transcription was threefold greater than that of alpha gene transcription. Treatment of animals bearing tumor IAK 109F with the same dose of T3 for 30 min did not significantly affect alpha or TSH-beta gene transcription, but at 2 hr alpha and TSH-beta RNA synthesis had decreased to 50% and 10% of control values, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4042814 TI - Detection of specific DNA sequences with short biotin-labeled probes. AB - We have developed a simple, general synthesis of nonradioactive DNA probes in which biotin is attached to the 5'-terminal phosphate of an oligodeoxyribonucleotide 16 bases long via an ethylenediamine or hexamethylenediamine linker. The products are stable under normal hybridization conditions. They hybridize to target DNA as efficiently as the underivatized oligodeoxyribonucleotide. Color development, using a commercially available kit, is complete within 3 hr using the biotin-detection method. The sensitivity of detection of homologous DNA with a probe to which biotin was attached via a hexamethylenediamine linker is about one-tenth of that achieved overnight by autoradiography with the corresponding 32P-labeled probe. PMID- 4042815 TI - Six cases of central serous choroidopathy induced by systemic corticosteroid therapy. AB - We report 6 cases of central serous choroidopathy (including pigment epithelial detachment in one case) which appeared in the course of systemic corticosteroid administration conducted to cure concurrent general diseases, and in one patient with a steroid-releasing pituitary adenoma. The majority of cases arose within about one month following the administration of more than 200 mg of prednisolon. It is postulated that corticosteroids operate as a kind of stress intervening in the hypophysis-adrenal system, leading eventually to the development of central serous choroidopathy. PMID- 4042816 TI - Retinitis-pigmentosa-like tapetoretinal degeneration in a rabbit breed. AB - By chance, we found a rabbit strain with retinal dystrophy. The eyes of these rabbits were examined by ophthalmoscopy, electroretinography, histology, and cytology--the latter after retina dissociation with papaine. The results suggest this rabbit strain to be a possible animal model for human retinitis pigmentosa. PMID- 4042818 TI - Electrophysiological studies on Kirisawa type uveitis (acute retinal necrosis). AB - Kirisawa type uveitis (acute retinal necrosis) is characterized by a necrotizing retinitis, heavy vitreous opacities, retinal vasculitis, and subsequent retinal detachment. Not only the etiology but also the clinical findings of this disease have not yet been defined. In the preceding year we have seen four patients whose clinical course and findings were similar to each other. In two of them a vitrectomy and an encircling operation have been performed before retinal detachment occurred. This treatment has found to be effective. In all 4 cases electrophysiological examinations were done at various stages of the disease. ERGs following pattern and flash stimuli varied in accordance with retinal changes, while VECPs were less strongly affected as ERGs. Results are discussed referring to fluorescein angiographic findings and ocular changes. PMID- 4042817 TI - Multiple sclerosis: abnormalities in luminance, chromatic, and temporal function at multiple retinal sites. AB - Visual function was assessed in a group of patients with multiple sclerosis (MS) and in a group of matched normal controls. In these patients the disease was relatively mild. For each subject, measures of a range of psychophysical visual functions were carried out at multiple sites in each eye. Previous reports have only included some of these functions. Here, luminance threshold, two-flash resolution, perceptual latency, luminance critical flicker frequency (CFF), and chromatic CFF were all measured. Variabilities of these functions and correlation between chromatic and luminance CFFs were also evaluated. For both the MS group and the normal control group, the correlations between pairs of visual parameters were not overall significantly greater than chance level. The MS group did give a significantly reduced value relative to the normal group for luminance CFF and for the gradient of the plot of chromatic CFF against luminance CFF. This group was then subdivided according to history of visual involvement. The subgroup with previous visual symptoms had significant impairment for luminance threshold, variability of luminance threshold, luminance CFF, variability of two-flash resolution, and for the gradient of the plot of chromatic CFF against luminance CFF. The subgroup without previous visual symptoms showed no significant impairment for any individual parameter, although the gradient of the plot of chromatic CFF against luminance CFF was lower than normal. PMID- 4042819 TI - The C-wave in hereditary degenerations of the ocular fundus. AB - The c-wave of the human direct current ERG may give new insights about the involvement of the retinal pigment epithelium in hereditary degenerations. In our single-sweep recordings from 236 alert patients we saw reduced c-waves not only in vitelliforme macular degenerations but also in dominantly inherited drusen, Stargardt's disease, cone dystrophies, and x-linked retinoschisis. In achromatopsia the c-wave was close to normal. The relationship of the b- and c wave, however, was altered only in Best's disease, cone dystrophy, and x-linked retinoschisis. We postulate that the c-wave when more severely reduced than the b wave reflects not merely the dysfunction of the pigment epithelium but more precisely whether this retinal layer is involved earlier than the photoreceptors. PMID- 4042820 TI - Electrophysiological analysis of Stargardt's disease fundus flavimaculatus group. AB - Stargardt's disease-fundus flavimaculatus has four general distribution patterns in fundus appearance: (1) macular degeneration without flecks; (2) macular degeneration with perifoveal flecks; (3) macular degeneration with diffuse flecks; and (4) diffuse flecks without macular degeneration (Noble and Carr, 1979). Four cases corresponding each to the four subgroups were studied electrophysiologically by our new tests for the cone receptor cell (rapid off response in the ERG) and for the retinal pigment epithelium (the hyperosmolarity response and the Diamox response). The results of our electrophysiological tests appear consistent with the histological findings by Klien and Krill (1967) and by Eagle et al. (1980), showing that the primary defect of fundus flavimaculatus is in the retinal pigment epithelium. Electrophysiologically, the severity of the disease correlated well with each fundus pattern. PMID- 4042821 TI - Electrophysiological similarities between two eyes with X-linked recessive retinoschisis. AB - Electroretinograms (ERG) and electro-oculograms (EOG) were studied in 88 eyes of 44 male patients with X-linked recessive retinoschisis. Differences of fundus appearance, ERG, and EOG between the eyes of each patient were analyzed. Fundus abnormalities were symmetrical in 77.3% of the cases. The amplitude of the ERG a wave was normal in 26.1% and was abnormally low in 73.9%. The amplitude of the b wave was below normal in all eyes; thus a small b-wave/a-wave ratio, which is characteristic of X-linked recessive retinoschisis, was observed in every case. The light peak to dark trough (LP/DT) ratio of the EOG was normal in 90.8% of the cases. The relative electrophysiological differences between the two eyes were calculated and showed that a-wave amplitude was not different between eyes in 75.0% of the cases; b-wave amplitude was not different in 77.3% of the cases; b wave/a-wave ratio was symmetrical in 93.2% of the cases; and the LP/DT ratio was consistent between eyes in 86.8% of the cases. These results suggest that in most cases of X-linked recessive retinoschisis the fundus appearance, ERG, and EOG are similarly affected in both eyes of the patient. PMID- 4042822 TI - Disease-specific electrophysiological findings in adult ceroid-lipofuscinosis (Kufs disease). AB - Two adults with mild dementia and a history of memory loss and disequilibrium were seen in the eye clinic following complaints of acuity loss in the 20/30 20/70 (Snellen) range. Results from the fundus examination of one patient were entirely normal; the other showed minimal vascular attenuation and optic atrophy. Electrophysiology was remarkable: (1) Photopic ERG b-waves were reduced, delayed, and showed pronounced oscillations. (2) EOG 'light-rise' potentials were absent or very small. (3) Binocular pattern-VER signals showed addition of the monocular signal. Scotopic ERG signals were normal. Brain biopsy and microscopy showed intercellular, autofluorescent ceroid deposits which provided a clear diagnosis of Kufs disease. Histology of model animal retinal cells show ceroid deposits in cell classes implicated by the human retinal signals. The cluster of electrophysiological results point toward early changes in the pigment epithelium and inner plexiform layer cells as a means of noninvasive diagnosis. PMID- 4042823 TI - Menkes' kinky hair disease: clinical and experimental study. AB - A pedigree of Menkes' kinky hair disease (MKHD) is reported. One patient of this family who underwent copper treatment was followed for three years with fundus examinations and ERG measurement. The blood copper level remained normal after six months of age, when intravenous treatment was switched from cupric acetate to cupric sulfate. Optic nerve atrophy and decrease in amplitude of the ERG were observed at three years of age. In an experiment using mouse models of MKHD (macular mouse mutant, Moml), we compared the affected mice that received copper treatment with normal mice. However, there was no difference between them in ERG responses, number of ganglion cells, or thickness of retinal layers. These results support the possibility of prolonged survival and maintained vision in the patients of MKHD by earlier normalization of the copper level. PMID- 4042824 TI - Hereditary retinal degeneration in the Abyssinian cat: correlation of ophthalmoscopic and electroretinographic findings. AB - Ophthalmoscopic and electroretinographic (ERG) findings were correlated in a group of Abyssinian cats affected by a slowly progressive and hereditary retinal degenerative disease. According to ophthalmoscopic findings the disease was divided into stages. At stage 1 and 2 retinal changes were minor; showing a gray discoloration most often in the peripheral and midperipheral tapetal fundus. At stage 3 discoloration was generalized and there was marked vascular attenuation. A generalized retinal atrophy was found at stage 4. ERG recordings showed an abnormally depressed stimulus response curve for the b-wave at stage 1 of disease when 30-Hz cone flicker responses were indistinguishable from normal. With progression of disease there was a successive decrease of a- and b-wave amplitudes before there was a significant reduction also of the c-wave amplitude (first seen at stage 3). The ERG was nonrecordable at stage 4. These findings suggest that the photoreceptors are affected primarily by the disease, before there is a functional involvement also of the pigment epithelium. The rod system seems to be affected early in the disease as compared with the cone system. A staging of the disease by ophthalmoscopy correlated more to the function of the rods than to that of the cones. PMID- 4042825 TI - Dark- and light-adapted visual evoked cortical potentials in retinitis pigmentosa. AB - Fifty patients with all genetic types of retinitis pigmentosa (RP) were tested with the visually evoked cortical potential (VECP) by full-field flashes of blue and red light in the dark-adapted state and white light flashes in the light adapted state. VECPs were recorded in all but one of these patients, even those with only a few degrees of central visual field remaining. In a subgroup of patients the absence of the VECP to blue light, dark-adapted, was correlated with a final dark-adapted threshold at or above cone threshold. These observations suggest that the VECP may be a useful objective method of assessment of patients with RP especially patients without detectable ERGs. PMID- 4042826 TI - Recording neuromagnetic fields in retinitis pigmentosa. AB - After stimulation of the left and right half-fields, it is possible to record contralateral visually evoked neuromagnetic fields (VEF) without any reference to the size of the half-field stimulus display. The test reacts extremely sensitively upon each shifting of the half field into the periphery to the left or right. By application of half-field pattern stimuli of an extremely high or low spatial frequency, characteristic deviation angles are obtained for both the spatial frequencies after evaluation of the VEF amplitudes. By this method the foveal acuity in RP can be investigated with an objective procedure to a very high degree of accuracy. PMID- 4042827 TI - Rod-cone interactions in the ERG of a patient with Bardet-Biedl syndrome. AB - During routine ERG testing of a patient with Bardet-Biedl syndrome, we encountered an ERG anomaly not previously reported. A white flash which produced a response during light adaptation would produce no ERG when the retina was dark adapted. Possible explanations for this phenomenon are discussed. PMID- 4042828 TI - Selective abnormality of the cone B-wave in a patient with retinal degeneration. AB - A 44-year-old woman with midperipheral pigmentary changes that resemble retinitis pigmentosa (RP) is described; unlike typical patients with RP, her photopic b wave was markedly attenuated as compared with her photopic a-wave. Otherwise, her electroretinogram (ERG) was typical of patients with early stages of photoreceptor degeneration. Scotopic and photopic a-wave amplitudes were reduced about 50%; her scotopic b/a appeared normal. PMID- 4042829 TI - Temporal aspects of the electroretinogram in cone-rod dystrophy. AB - Twelve patients with cone-rod dystrophy were studied in terms of the temporal aspects of electroretinography (ERG). The peak time of scotopic b-wave was within normal limits in all patients, while the amplitude was reduced in nine patients. The normal peak time of the scotopic-b wave may help explain rod involvement with normal or only slightly elevated final rod thresholds of subjective dark adaptation. The peak time of photopic b-wave and 30-Hz flicker response was normal in four patients and significantly delayed or nonrecordable in eight patients. Such variations of peak time in photopic and 30-Hz flicker ERG may reflect the stage of the disease or may be caused by the different hereditary mode. PMID- 4042830 TI - [Preferential initiation of unscheduled DNA synthesis on areas associated with the nuclear matrix]. PMID- 4042831 TI - [Isolation and characteristics of a protein similar to ceruloplasmin from the serum of a patient with hepatolenticular degeneration (Wilson-Konovalov disease)]. PMID- 4042832 TI - [Partial purification of the polymerase of O-specific polysaccharide in Salmonella anatum]. PMID- 4042833 TI - [Participation of cytochrome P-448 in 3,4-benzopyrene metabolism during induction by different xenobiotics in inbred mouse strains]. PMID- 4042834 TI - [Evaluation of the intensity of endogenous lipid peroxidation in human beings under hyperbaric oxygenation]. PMID- 4042835 TI - [Action of alamethicin on the coupling membrane of mitochondria]. PMID- 4042836 TI - [Possible control of cardiac rhythm by voluntary change in respiratory rate]. PMID- 4042837 TI - [In vivo displacement of an antigen from its complex with a carrier polymer removes its immunogenicity]. PMID- 4042838 TI - [DNA nucleotide sequence of the actinomycete plasmid pSB24.2]. PMID- 4042840 TI - [Electrotonic modulation of T wave changes in 37 patients with pacemakers]. PMID- 4042839 TI - [Therapeutic effect of nifedipine in the treatment of systemic hypertension]. PMID- 4042841 TI - [Intra-atrial block]. PMID- 4042842 TI - [Evaluation of the conduction function in complete atrioventricular block patients with implanted pacemakers, by external chest stimulation]. PMID- 4042843 TI - [The variance in cardiac parameters after long-term physical labor]. PMID- 4042844 TI - [Analysis of arrhythmia and ST-T wave changes in 324 cases of COPD patients in the Qinghai highlands]. PMID- 4042846 TI - [Evaluating calcification in coronary arteries using TV fluoroscopy]. PMID- 4042845 TI - [Persistent left superior vena cava draining into the coronary sinus diagnosed by contrast echocardiography: a case report]. PMID- 4042847 TI - [Experimental research of papillary muscle infarction]. PMID- 4042848 TI - [Comparative study of the recovery processes of left ventricular pump function and myocardial contractility after experimental myocardial infarction]. PMID- 4042849 TI - [A specific method of suppressing sinoatrial nodal automaticity]. PMID- 4042851 TI - [Anatomical study of the coronary arteries in Tibetans]. PMID- 4042850 TI - [Experimental study on phasic conduction block]. PMID- 4042852 TI - [Mitral valve replacement with the Shanghai-made tilting disc prosthesis: a report of 222 consecutive cases]. PMID- 4042853 TI - [Multiple valve replacement: 59 cases]. PMID- 4042854 TI - [Postoperative endocarditis after pericardial prosthetic valve replacement: 6 cases]. PMID- 4042855 TI - [74 cases of mitral valve replacement using porcine prosthesis]. PMID- 4042856 TI - [Pseudosupernormal conductivity in atrioventricular conduction]. PMID- 4042857 TI - [Conduction disorders in the early postoperative period after open-heart surgery]. PMID- 4042858 TI - Long-term survival strategy for the pharmacy profession. PMID- 4042859 TI - Is ambulatory therapeutic digoxin monitoring useful? PMID- 4042860 TI - Central nervous system toxicity associated with concurrent use of triazolam and cimetidine. AB - A 49-year-old woman treated with cimetidine 300 mg tid for more than 18 months for Zollinger-Ellison syndrome experienced lethargy, dizziness, ataxia, and auditory and visual hallucinations after receiving triazolam 0.375 mg hs for sleep. Triazolam plasma concentrations were measured, and a triazolam elimination half-life was calculated to be approximately 8 hours (reported range 1.7-3 h). Cimetidine has been reported to decrease the apparent oral clearance of triazolam, resulting in increased triazolam plasma concentrations with the potential for exaggerated triazolam pharmacologic effects. Cimetidine may have been responsible for the unusually large elimination half-life in this patient. Until the mechanisms and clinical significance of this potential drug interaction are determined, clinicians should use the combination of triazolam and cimetidine with caution. PMID- 4042861 TI - Lidocaine-induced second-degree mobitz type II heart block. AB - Lidocaine-induced atrioventricular (AV) conduction disturbances are an ill defined phenomenon. Electrophysiological studies in both animal and human subjects have shown that therapeutic doses of lidocaine have no significant effect on AV nodal and His-Purkinje conduction time in the presence of intact AV conduction. Sporadic reports of accelerated AV conduction or complete heart block following lidocaine administration have been published. One case of Mobitz type II heart block has been reported in a patient with a prolonged QTc interval (0.61 sec) who was also receiving prenylamine. Electrophysiological studies designed to evaluate lidocaine's effects on AV conduction present conflicting observations. We report a case of Mobitz type II heart block following therapeutic doses of lidocaine in the absence of acute myocardial infarction or concomitant cardioactive drug administration. This case, in conjunction with other reported data, suggests the occurrence of lidocaine-induced AV block to be unpredictable. Although its occurrence may be infrequent, the severity of these reactions warrants careful selection and monitoring of patients who are to receive lidocaine. PMID- 4042862 TI - Ticlopidine as a hemorrhagic risk factor in coronary surgery. AB - We retrospectively reviewed the postoperative hemorrhagic risk in patients undergoing surgery for coronary revascularization who had received platelet antiaggregants preoperatively. A significant increase in postoperative hemorrhage and a higher percentage of reoperations for this reason was observed in the patients treated with ticlopidine. However, there were no major differences in the platelet counts among the groups compared. PMID- 4042863 TI - The lack of inactivation of tobramycin by cefazolin, cefamandole, and moxalactam in vitro. AB - We examined the effects of mixing tobramycin with three cephalosporins, cefazolin, cefamandole, and moxalactam. Each cephalosporin was prepared from standard powder and diluted with human serum to concentrations of 50, 250, and 500 micrograms/ml and added to 10 micrograms/ml of tobramycin in human serum. Temperature environments of 4 degrees C (refrigeration), 24 degrees C (room temperature), and 37 degrees C (body temperature) were used and sampled at 0 hours (control), and at 8, 24, and 48 hours. The results indicated no inactivation of tobramycin by any of the cephalosporins, regardless of temperature, concentration, or contact time. These results indicate that significant inactivation of tobramycin does not occur when it is combined in vitro with moxalactam, cefamandole, or cefazolin. PMID- 4042864 TI - Comment: Triazolam-cimetidine reaction. PMID- 4042865 TI - Comment: Cyclosporine and vaccination. PMID- 4042866 TI - Comment: Lidocaine seizures. PMID- 4042868 TI - Lorazepam--a benzodiazepine to choose or avoid? PMID- 4042867 TI - Comment: Indomethacin sustained-release. PMID- 4042869 TI - When to dissolve stones in the gallbladder. PMID- 4042870 TI - Routine six-monthly checks for dental disease? PMID- 4042871 TI - "Don't take your medicine lying down!". PMID- 4042872 TI - Rowachol for gallstone dissolution? PMID- 4042873 TI - Management of the dry eye. PMID- 4042874 TI - Combining hydrocortisone with an antifungal on the skin. PMID- 4042875 TI - Irritant contact dermatitis. Traumiterative and cumulative impairment by cosmetics, climate, and other daily loads. AB - Based on the results of exposure experiments on living human skin a working hypothesis is launched concerning the possible pathogenesis of irritant contact dermatitis. Below a certain and critical degree of exposure there is no alteration in clinical aspect of the exposed region. However, instrumentally (watervapour-loss measurements, impedance measurements) it is usually possible to register subclinical effects in such a field. These are interpreted as signs of impairment of metabolic homoiostatic systems. It is possible in certain cases to show that the skin is able to adapt its functions to a repeated load (illustrated with exposure experiments to DMSO). It seems useful to distinguish between a traumiterative irritant contact dermatitis (a result of too early repetition of just one type of load; see Aquabrom experiment) and a cumulative irritant contact dermatitis (resulting from a too early repetition of exposures differing in type; see experiment with soap and detergent solutions). In cumulative irritant contact dermatitis the sequence of the different loading factors is of importance: first soap and then detergent or the reverse. PMID- 4042877 TI - [Clinical importance of programming of cardiac pacemakers]. PMID- 4042876 TI - Guinea pig maximization test: effect of type of Freund's complete adjuvant emulsion and of challenge site location. AB - Guinea pig maximization tests (GPMT) with chlorocresol were performed to ascertain whether the sensitization rate was affected by minor changes in the Freund's complete adjuvant (FCA) emulsion used. Three types of emulsion were evaluated: the oil phase was mixed with propylene glycol, saline with 30% (v/v) ethanol or saline, respectively. Relative viscosity was used as one measure of physical properties of the emulsion. Higher degrees of sensitization (but not rates) were obtained at the 48 h challenge reading with the oil/propylene glycol and oil/saline + ethanol emulsions compared to the saline/oil emulsion. Placing of the challenge patches affected the response, as simultaneous chlorocresol challenge on the flank located 2 cm closer to the abdomen than the usual challenge site gave decreased reactions. PMID- 4042878 TI - [Programming of pacemakers: a gain or a passtime?]. AB - Seventy-seven programmable pacemakers, selected at random from a reservoir of 1051 explanted pacemakers, made available by health-offices, institutes of pathology and institutes of forensic medicine, were examined for alterations made since the time of delivery. The results motivated our choice of title. In 41 of 74 (55.4%) no parameter was changed and in 36.5% the frequency was altered. Of the two- or multi-programmable pacemakers, the amplitude was altered in 13 of 61 (21.3%), the pulse duration in 9 out of 38 (23.7%), the sensitivity in 10 out of 32 (31.3%), hysteresis in one out of 31 (3.2%) and the refractory time in none of 30. None of the 10 pacemakers with programmable operation mode were reprogrammed although they included a DDD that was delivered, however, in the VVI state. Nine of 69 pacemakers (13%) were double- and 2 of 33 (6%) triple-programmed. The two physiological parameters (frequency and hysteresis) were clearly not utilised to the extent that would be desirable. All other programmable parameters serve exclusively for the technical adjustment to the heart. PMID- 4042879 TI - [Hyperimmunoglobulinemia E, recurring staphylococcal infections and a defect in granulocyte chemotaxis in adults. A variant of Job's syndrome]. AB - Two cases in adults with recurrent staphylococcal infections associated with abnormal granulocytic chemotaxis and hyperimmunoglobulinaemia E (Job's syndrome) are described. The pathophysiological mechanisms seems to consist of an abnormal IgE reaction against staphylococcal antigens causing secondary abnormality of granulocyte function. Abnormal cellular immune function was demonstrated in vitro and in vivo. Corticosteroid administration at first proved effective in both patients. One patient developed Hodgkin's disease of the mixed type in the course of the disease. PMID- 4042880 TI - [The physician's obligation of assistance in hospital discharge against the physician's counsel]. PMID- 4042881 TI - [Suramin therapy in patients with LAS/AIDS]. PMID- 4042882 TI - [Endoscopic ultrasonic study of the esophagus]. PMID- 4042883 TI - [Hyperprolactinemia and prolactinomas. Results of surgical and drug therapy]. AB - 185 patients with hyperprolactinaemia and prolactinoma were evaluated in a retrospective investigation. 128 patients were treated surgically whereby the prolactin serum level in 47% of the macroprolactinoma and 60% of the microprolactinoma patients was normalised (prolactin less than 25 ng/ml, no radiological evidence of tumor). Of those patients in whom the operation was less successful, a normal prolactin level could be achieved in 77% by additional therapy with dopamine agonists. Of 57 patients handled exclusively with drugs, the prolactin level was normalised by dopamine agonists in 78%. A small number of patients from both groups did not show a satisfactory fall in the prolactin level despite the use of markedly higher doses of dopamine agonists. During dopamine agonist therapy progressive tumor enlargement was detected radiologically in a previously operated patient. PMID- 4042885 TI - [Diagnosis of pregnancy hypertension]. PMID- 4042886 TI - [The importance of medical journals in undergraduate, postgraduate and continuing medical education]. PMID- 4042884 TI - [Therapeutic possibilities in hypereosinophilia syndrome with Loffler's fibroplastic endomyocarditis. Efficacy of cytarabine and 6-thioguanine]. AB - In two of four patients with hypereosinophilia and Loffler's myocarditis (confirmed by biopsy) the activity of the disease was contained with prednisone, in one instance combined with hydroxycarbamide. In two patients, in whom the disease was taking a fulminant course and other treatment had failed, cytarabine and 6-thioguanine proved effective, providing a 16-month symptom-free period in one of them. But the second patient died from septicaemia associated with treatment-induced bone-marrow hypoplasia. Prednisone (1 mg/kg daily) and hydroxycarbamide (0.5-1.5 g daily) are the drugs of choice in the hypereosinophilia syndrome. If they fail, cytarabine (100 mg/m2 on days 1-5, repeated on day 28) and 6-thioguanine (100 mg/m2 daily) should be given. PMID- 4042887 TI - [Liability of the hospital physician in inadequate care of patients]. PMID- 4042888 TI - [Antidote therapy in poisonings by calcium antagonists]. PMID- 4042889 TI - [Occlusion of a tumor fistula in the rectum with Ethibloc]. PMID- 4042890 TI - [Acute polyneuropathy after inhalation of solvent mixtures]. PMID- 4042892 TI - [Management of arterial hypertension in acute myocardial infarct]. PMID- 4042891 TI - [Errors and hazards: fatalities through sternal puncture]. AB - Iatrogenic cardiac injury due to diagnostic sternal puncture occurred in 5 patients, 2 women and 3 men, aged 14 to 37 years. Four cases ended fataly but 1 patient survived after immediate thoracotomy and suture of the damaged heart. Perforation of the anterior wall of the right ventricle resulting in pericardial tamponade was present in all patients. All fatalities resulted in conviction, under criminal law, of the clinician who carried out the puncture (Paragraph 222 StGB--causing death through negligence). PMID- 4042893 TI - [Legislation concerning the profession of midwives and delivery assistants 1985]. PMID- 4042894 TI - [AIDS in schoolchildren]. PMID- 4042895 TI - [Blood exchange instead of plasmapheresis in severe tropical malaria]. PMID- 4042897 TI - [The problem of "pluriglandular insufficiency"]. PMID- 4042896 TI - [Hypersensitivity phenomena in dialysis patients. Incidence of eosinophilia, raised IgE and ethyleneoxide-induced antibodies]. AB - The hypersensitivity parameters eosinophil count, serum IgE and IgE-type antibodies to ethylene oxide-albumin conjugates (ETO-antibodies), were determined in 182 dialysis patients. Eosinophilia was seen in 21.7% of patients, IgE elevation in 21.4% and ETO-antibodies in 12.4%. A pathological change in at least one of the measured parameters was present in 33.1%. The appearance of ETO antibodies was frequently associated with severe clinical symptoms, especially asthma and anaphylactic shock. Sensitisation is apparently common in dialysis patients. Since ETO-antibodies are often associated with severe clinical symptoms, their presence should be sought in those dialysis patients showing incompatibility reactions or asthma. PMID- 4042898 TI - [Gynecologic problems in teenagers]. PMID- 4042899 TI - [Polycystic ovaries]. PMID- 4042900 TI - [Therapy of infertility]. PMID- 4042901 TI - [In vitro fertilization]. PMID- 4042902 TI - [Disorders of the menstrual cycle]. PMID- 4042903 TI - [Precancerous lesions of the uterine cervix]. PMID- 4042904 TI - [Urinary incontinence]. PMID- 4042905 TI - [Ovarian cancer--the gynecologist's greatest challenge]. PMID- 4042906 TI - [Gynecological problems after the menopause]. PMID- 4042907 TI - A physician's view of dysthyroid disease. PMID- 4042908 TI - Radioactive iodine therapy of thyrotoxicosis. PMID- 4042909 TI - Anesthesia for thyroid surgery. PMID- 4042910 TI - Radiotherapy for thyroid tumors and thyrotoxicosis. PMID- 4042911 TI - Management of malignancy of the thyroid gland. PMID- 4042912 TI - Juvenile rhabdomyosarcoma of middle ear and mastoid. PMID- 4042913 TI - Penetrating injuries of the larynx. PMID- 4042914 TI - Open rhinoplasty. PMID- 4042915 TI - Rhinolithiasis and maxillary antrolithiasis. PMID- 4042917 TI - The endolymphatic sac operation for Meniere's disease. PMID- 4042916 TI - Petrous apicitis. PMID- 4042918 TI - Temporal bone involvement in Waardenburg's syndrome. PMID- 4042920 TI - Foreign body in the bronchus--an unusual case. PMID- 4042919 TI - A comparison of nasal balloons and posterior gauze packs for posterior epistaxis. PMID- 4042921 TI - Clinical presentation of congenital ichthyosis in two newborns seen at Kenyatta National Hospital (KNH). PMID- 4042922 TI - Epidemiology of jaw tumours in Nyanza Province with special reference to Burkitt's lymphoma: report of preliminary findings at the Nyanza General Hospital, Kisumu, Kenya. PMID- 4042923 TI - Neurological disturbances in sickle cell disease in children in Zaria, Nigeria. PMID- 4042924 TI - Foetal erythrocytes in the circulation of pregnant Nigerian women. PMID- 4042925 TI - An unusual cause of maternal mortality in homozygous sickle cell anaemia in pregnancy: case report. PMID- 4042926 TI - 100 years of post-exposure rabies vaccination. PMID- 4042927 TI - Severe depression treatment: experience using maprotiline (Ludiomil) in combination with clomipramine (Anafranil). PMID- 4042928 TI - Management of rape victims in Benin City, Nigeria. PMID- 4042929 TI - Immune complexes and immunoglobulins in Nigerian patients with typhoid fever. PMID- 4042930 TI - Psychiatric disorders in a general provincial hospital in Kenya. PMID- 4042931 TI - Perinatal mortality surveys in an African teaching hospital: I. The past and present statistics. PMID- 4042932 TI - Estimation of median age of eruption of permanent teeth in Kenyan African children. PMID- 4042933 TI - Human Salmonella serotypes in Uganda, 1967-1982. PMID- 4042934 TI - Shigella serotypes in Uganda, 1967-1982. PMID- 4042936 TI - Emetine hydrochloride in the treatment of scorpion stings. PMID- 4042935 TI - A clinical, biochemical and histochemical study of carcinoma of the cervix as seen at the Kenyatta National Hospital. PMID- 4042937 TI - A locally made external fixator. PMID- 4042938 TI - Disseminated histoplasmosis in a Kenyan African child: a case report. PMID- 4042939 TI - Feeding pattern, supplementary foods and growth of low birthweight and normal birthweight infants in Machakos, Kenya. PMID- 4042940 TI - Cerebrovascular accidents in 207 Kenyans; general peculiarities and prognosis of stroke in an urban medical centre. PMID- 4042941 TI - The experience of foreign body inhalation among children at Kenyatta National Hospital over a five-year-period. PMID- 4042942 TI - Serum cholesterol studies in healthy Nigerian children. PMID- 4042943 TI - The problems with the management of carcinoma of the cervix in Nigeria--Lagos experience. PMID- 4042944 TI - The health status of children in a rural community in north eastern Zambia. PMID- 4042945 TI - The origins of bad breath (fetor oris) from the oral cavity and its management. PMID- 4042946 TI - Hypertension over a 4-year-period at Kenyatta National Hospital (KNH). PMID- 4042947 TI - Cell-mediated immunity to spermatozoal antigens after vasectomy: recent developments. PMID- 4042948 TI - The role of bacterial pathogens in pre-operative sepsis of acute mural appendicitis. PMID- 4042949 TI - Allergen skin tests to asthmatic children screened at Muhimbili Medical Centre, Dar es Salaam, Tanzania. PMID- 4042950 TI - Systemic lupus erythematosus at Kenyatta National Hospital 1972-1984. PMID- 4042951 TI - Post-pneumonectomy oesophagopleural fistula. PMID- 4042953 TI - Current practice. Choosing variables in research in clinical medicine. PMID- 4042952 TI - Rhinoscleroma--case report. PMID- 4042954 TI - [Pathogenesis, clinical aspects and development of fatty liver]. AB - Anamnestic, clinical, biochemical and bioptic examinations were performed in 127 patients with fatty infiltration of the liver of different degrees of severity. Anamnesis, clinical practice and laboratory findings can only throw the suspicion on the fatty infiltration of the liver. For the verification of the diagnosis and for the gradation first of all the liver biopsy is necessary. Alcohol clearly plays the most important part as a cause of the development of the fatty infiltration of the liver, followed by adiposity, diabetes and hyperlipoidaemia. Because of the great medical and social-economic importance fatty infiltration of the liver cannot longer be taken for a harmless disurbance. PMID- 4042955 TI - [Bronchobiliary fistula as sequela of the stenosis of hepaticojejunostomy]. AB - This is a case report on a bronchobiliar fistula after frequent recurrences of cholangites following an occlusion of a hepaticojejunostoma. Sufficient drainage and correction of the stenosis as well as balancing of water and electrolyte metabolism were without any therapeutic success. The patient died in consequence of an acute liver dystrophy. PMID- 4042956 TI - [Effect of cimetidine on maximal stomach secretion in physical stress and at rest in patients with chronic duodenal ulcer]. AB - In 21 males suffering from chronic duodenal ulcers the effect of cimetidine on the maximum acid output (MAO) both in rest and under physical load was examined. Patients were loaded two times (60 min) with the Monark bicycle ergometer at an interval of 5-7 days. Immediately before second examination cimetidine was injected intravenously (6 mg/kg body weight). The sampling of gastric juice was done 3 times for 60 min before, during and after the physical work. In the stimulated gastric fluid the concentrations of sodium, potassium, chlorid ions, total protein and mucoproteins were checked. In the peripheral venous blood sodium, potassium, chlorid, magnesium and calcium were measured as well as glucose and the parameters of acid base state. Cimetidine significantly reduced ionic concentration, protein and mucoproteid concentrations of the gastric fluid. Cimetidine did not provoke any changes of the parameters determined in the peripheral blood. PMID- 4042957 TI - [Effect of glucose on fetal weight and the transplacental blastomogenic effect of N-nitrosomethylurea in rats]. AB - The N-nitrosomethylurea (NMU)-induced transplacental blastomogenesis in rats was studied under the effect of pre- and postnatal glucose administration. On the 21st day of pregnancy NMU (20 mg/kg) was intraperitoneally administered to rats. From the 7th day of pregnancy experimental rats were treated with 10% glucose solution instead of drinking water, and during 1.5 months after delivery they and their progeny were given 5% glucose solution. The foetal weight in glucose treated pregnant rate increased. A significant increase of tumour frequency was detected in the progeny of these rats. In male progeny tumours of the nervous system and kidneys typical of NMU effect prevailed and in females--tumours of other organs and tissues, particularly of the mammary gland, pituitary and hemopoietic system. Possible mechanisms of the modifying effect of glucose on the transplacental blastomogenic action of NMU are discussed. PMID- 4042958 TI - [Kinetics of the cell population in adenocarcinoma 755 after cyclophosphane administration and rate of tumor growth after an additional course of therapy with cyclophosphane and 6-mercaptopurine]. AB - The two injections of cyclophosphane (100 mg/kg) to mice with adenocarcinoma 755 on the 6th and 11th days after tumour transplantation had no influence on the cell cycle but induced a decrease of its growth rate due to an increase in the level of cell losses. The third cyclophosphane injection (the same dose) on the 17th day after the tumour transplantation or an additional course of five 6 mercaptopurine injections (50 mg/kg each dose) did not change essentially the growth rate of tumours. PMID- 4042960 TI - [Colony-forming ability of lymph node fibroblasts in patients with malignant lymphomas]. AB - Determination of the efficiency of fibroblasts' colony-formation in patients with Hodgkin's disease, non-Hodgkin's malignant lymphomas and reactive lymphoid hyperplasia reveals that the colony-forming ability of fibroblasts does not depend on the nature of the pathological process, but depends on the morphofunctional status of the lymphoid tissue. It is found that single determination of fibroblasts colony-formation efficiency cannot be used as a prognostic feature for determination of the further course and outcome of the disease. PMID- 4042959 TI - [Cytological characteristics of carminomycin-resistant P-388 lymphoid leukosis]. AB - The carminomycin-resistant strain (P-388/c) of P-388 lymphoid leukemia is obtained. Resistance development is accompanied by higher sensitivity to cytostatics, rise of hyperploidy, replacement of the stem line, presence of definite markers in leukemic cells as well as by the appearance of a clone of cells with higher dry mass. At the level of CFUs after the carminomycin administration more remote terms of cell restoration than in case of P-388/c lymphoid leukemia are determined. The P-388/c lymphoid leukemia cells lost their sensitivity to carminomycin at the stage of the DNA synthesis. Accumulation of cells is observed in phase G2 of the mitotic cycle. PMID- 4042962 TI - Evidence for induction by thyroid hormone of cytosolic proteins which control mitochondrial protein synthesis. AB - The effect of thyroid hormone on the generation of modulators of mitochondrial protein synthesis was investigated. The modulators were present in the 150,000 X g supernatant (S-150) prepared from Wistar rat liver and kidney. In young rats (50 g BW), a stimulator was found in liver, and an inhibitory modulator was present in kidney tissue. Generation of these modulators was stimulated by T4 administration to the animals. In aged rats (200 g BW), the production of an inhibitory modulator in both liver and kidney was stimulated by thyroid hormone administration. Both the stimulatory and inhibitory modulators were inactivated by pretreatment with trypsin. The mol wt of these modulators was estimated by gel filtration study, and for both the stimulatory and inhibitory modulator proteins was approximately 10,000. The results suggested that thyroid hormone regulates mitochondrial protein synthesis through the stimulation of synthesis of mitochondrial protein synthesis modulators and that the tissue-specific modulators (stimulatory in liver and inhibitory in kidney) can be produced in young animals. In aged animals, however, it is postulated that thyroid hormone stimulates biosynthesis of an inhibitory modulator in both liver and kidney. PMID- 4042961 TI - Effect of dopamine agonists and antagonists on the binding of [3H]estradiol to its receptors in the anterior pituitary gland of male rats. AB - The synthesis of PRL and DNA in PRL cells is regulated by estrogens and dopamine. To investigate a possible relationship between these two components, we studied the influence of dopamine agonists and antagonists on the binding of [3H]estradiol ([3H]E2) to its receptors in the anterior pituitary gland of estrogenized male rats. The administration of sulpiride (dopamine antagonist) or bromocriptine (dopamine agonist) decreased the binding of [3H]E2 to cytosolic receptors when the concentration of [3H]E2 in the assay mixture was 1 nM. Both drugs also diminished the binding of [3H]E2 when they were added in vitro to the incubation media, apparently in a competitive way. Dopamine and alpha methyltyrosine also inhibited competitively the binding of [3H]E2 to cytosolic receptors. The inhibition constants were determined by the Lineweaver-Burk plot. To overcome the competitive inhibition of dopamine agonists and antagonists, the concentration of the titrated steroid in the incubation mixture was increased to 16 nM. This concentration was established by saturation analysis. The administration of alpha-methyltyrosine increased the binding of [3H]E2 to nuclear receptors without modifying the binding to cytosolic receptors. This increase paralleled an increment in the levels of plasma PRL. Bromocriptine prevented the increase in [3H]E2 binding produced by alpha-methyltyrosine and had no effect on the binding when administered to nontreated rats. These results suggest that dopamine can regulate the biological effects of estradiol in the anterior pituitary gland by decreasing the binding of this hormone to its receptors. PMID- 4042963 TI - Restoration effects of exogenous luteinizing hormone on the testicular steroidogenesis and Leydig cell ultrastructure. AB - In the present study, we explored the restoration effects of exogenous LH on Leydig cell ultrastructure and testicular steroidogenesis in rats that were deprived of endogenous LH via treatment with testosterone-17 beta-estradiol filled Silastic implants for 10 days. Exogenous LH was supplied continuously via Alzet miniosmotic pumps at the rate of 1 microgram/h for 3, 6, 12, and 24 h or 1, 2, 4, 8, and 12 days. Testes were then perfused in vitro with medium containing 1) LH, 2) 20 alpha-hydroxycholesterol, or 3) pregnenolone substrate, which allowed us to assess LH-stimulated testosterone secretion, cholesterol side-chain cleavage activity, or the conversion of pregnenolone to testosterone, respectively. Other testes were perfusion fixed via the testicular artery for morphometric measurement of Leydig cell number and volume per testis and the surface area of Leydig cell cytoplasmic smooth endoplasmic reticulum (SER), inner mitochondrial membrane, and outer mitochondrial membrane. The results verified that Leydig cell smooth endoplasmic reticulum and inner and outer mitochondrial membrane surface areas are drastically diminished (P less than 0.05 vs. intact controls) by LH withdrawal. Also, the results verified that exogenous LH administered in situ restores Leydig cell ultrastructure and capacity to biosynthesize testosterone. However, the recovery of Leydig cell structure and steroidogenic reactions occurred at strikingly different rates upon restoration of LH after 10 days of the treatment with testosterone-17 beta-estradiol implants. For example, the restoration of testicular capacity to synthesize progesterone in response to LH stimulation or 20 alpha-hydroxycholesterol substrate was completed within 24 h. In contrast, the restoration of Leydig cell SER and testicular capacity to synthesize testosterone from pregnenolone was completed only after 8 days of continuous LH treatment (P greater than 0.05 vs. intact controls). Thus, our results show that LH rapidly restores Leydig cell post-LH receptor steroidogenic events up to and including cholesterol side-chain cleavage activity. Interestingly, there is no temporal association between the recovery of cholesterol side-chain cleavage activity and the surface area of inner mitochondrial membrane surface area. In contrast, 8 days are required to coincidentally restore SER surface area and the capacity of Leydig cells to synthesize testosterone from pregnenolone. We conclude that different cellular mechanisms are involved in the LH-dependent restoration of inner mitochondrial cholesterol side-chain cleavage activity and SER-associated conversion of pregnenolone to testosterone. PMID- 4042964 TI - Mapping of glucocorticoid receptor immunoreactive neurons in the rat tel- and diencephalon using a monoclonal antibody against rat liver glucocorticoid receptor. AB - By means of a monoclonal antibody against the rat liver glucocorticoid receptor (GR) in combination with the indirect immunoperoxidase technique it has been possible to demonstrate GR-immunoreactive nerve and glial cell nuclei all over the tel- and diencephalon of the male rat. Strongly GR-immunoreactive nerve cell nuclei were only present in the parvocellular part of the paraventricular hypothalamic nucleus, in the anterior periventricular hypothalamic nucleus, in the ventral part of the mediobasal hypothalamus, and in the CA1 and CA2 subregion of the hippocampal formation. Within the paraventricular hypothalamic nucleus a substantial overlap exists between the GR-immunoreactive area and the CRF immunoreactive area. Medium to high densities of moderately GR-immunoreactive nerve cell nuclei were present all over the cortical hemispheres. Medium densities of moderately GR-immunoreactive nerve cells were demonstrated in many thalamic nuclei and in the central amygdaloid nucleus. After adrenalectomy the GR immunoreactivity was predominantly located in the pericaryon. Upon acute corticosterone treatment of adrenalectomized male rats, the GR immunoreactivity was again mainly demonstrated in the nerve cell nuclei indicating that corticosterone can translocate GR from the cytoplasm to the cell nuclei. It is suggested that the hypothalamic GR may be involved in the regulation of especially CRF secretion but also in the secretion of other anterior pituitary hormones such as TRH and somatostatin. PMID- 4042965 TI - Interaction of estradiol and estriol with uterine estrogen receptor in vivo and in excised uteri or cell suspensions at 37 C: noncooperative estradiol binding and absence of estriol inhibition of estradiol-induced receptor activation and transformation. AB - The partial agonist and antagonist properties of estriol (E3) have been related to the brief nuclear retention of receptor-E3 complexes and to the lower affinity of E3 for the receptor compared to estradiol (E2). More recently, it was proposed that the partial agonist/antagonist activity of E3 may be due to its ability to eliminate positive cooperative binding of [3H]E2 to cytosolic estrogen receptor. In this model, positive cooperativity is related to receptor activation and transformation. We first examined the long term effects of E3 on E2 action in vivo. Mature ovariectomized rats were treated for 16 days with E2, E3, or mixtures of these two substances delivered through Alzet pumps at a constant hourly rate (E2, 0.04 microgram; E3, 0.4 and 0.04 microgram; E2 and E3, 0.04 and 0.4 microgram). The effects of E3 on uterine growth, induction of progesterone receptor synthesis, and activation (nuclear binding) of estrogen receptor suggest that when given continuously, E3 acts as a full agonist and does not inhibit E2 action. Furthermore, incubation of uteri at 37 C with [3H]E2 in the presence of a 1- to 20-fold molar excess of nonradioactive E3 did not alter the subcellular distribution of receptor-[3H]E2 complexes (80% nuclear and 20% cytosolic), demonstrating that E3 does not inhibit E2-induced receptor activation (i.e. the increased nuclear binding of receptor). Similarly, 4S to 5S transformation of [3H]E2-labeled estrogen receptor in intact uteri was not inhibited by E3. Equilibrium binding of [3H]E2 to uterine cell suspensions at physiological temperature (37 C) was noncooperative; nonradioactive E3 did not alter the affinity of the estrogen receptor for [3H]E2; Dixon plot analysis indicates that E3 is a purely competitive inhibitor of [3H]E2 binding. This, in conjunction with the lower affinity of the receptor for E3 than for E2, adequately explains the agonistic-antagonistic properties of E3.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4042966 TI - Abnormal thyroid hormone binding to serum proteins in ob/ob and db/db genetically obese mice. AB - Sera from ob/ob and db/db genetically obese mice exhibited abnormal nonspecific (no antibody present) binding measurements in T4 and T3 RIAs employing dextran charcoal separations. They also showed decreased charcoal uptake compared to sera of lean controls in a conventional charcoal T4 uptake binding test. After correction for the abnormal nonspecific binding and after extraction of serum, mean serum T4 concentrations were similar in control and ob/ob mice. Mean serum T3 concentrations differed significantly (85 ng/dl in controls and 178 ng/dl in ob/ob) when a correction for altered binding in the T3 assay was made, but not when extracted serum was assayed (109 ng/dl in lean and 124 ng/dl in ob/ob). Dialyzable fractions of T4 and T3 were significantly reduced in both ob/ob and db/db mice. Free T4 concentrations were 0.82 +/- 0.05 (+/- SE) ng/dl in control and 0.61 +/- 0.05 ng/dl in ob/ob sera (P less than 0.01). Polyacrylamide gel electrophoresis showed increased binding of tracer T4 and T3 in ob/ob and db/db sera to a postalbumin with mobility similar to that of human T4-binding globulin. In ob/ob sera, this appeared to result from an increased binding capacity of the postalbumin. After in vivo iv injection of tracer T4 and T3 to ob/ob and lean control mice, analysis of tissue and plasma radioactivity showed that, except for T4 in cerebral cortex, tissue to plasma T4 and T3 ratios were lower in cerebral cortex, cerebellum, and liver of ob/ob mice. In summary, these data show increased binding of T4 and T3 to a postalbumin in two strains of genetically obese mice and, in the ob/ob strain, complex relationships between tissue and serum concentrations of thyroid hormones. PMID- 4042967 TI - Cholera toxin treatment increases in vivo growth and development of the mouse mammary gland. AB - Daily sc injections of cholera toxin (CT; 0.1 micrograms/day), a stimulator of adenylate cyclase activity, into intact female BALB/c mice for 20 days significantly (P less than 0.05) increased mammary gland development scores from 2.0 +/- 0.1 in controls to 3.6 +/- 0.2 in CT-treated mice. Concurrent administration of 17 beta-estradiol (E; 1.0 microgram/day) and progesterone (P; 1.0 mg/day) resulted in development scores of 4.1 +/- 0.1 and 5.2 +/- 0.1 in E/P and E/P + CT treatment groups, respectively (P less than 0.05). If mice were ovariectomized before CT injection, the response to CT alone was abolished (development scores of 2.0 +/- 0.1 and 1.9 +/- 0.1 in controls and CT-treated mice, respectively). However, E/P restored the response to CT (scores of 3.2 +/- 0.2 for E/P and 4.0 +/- 0.1 for E/P + CT; P less than 0.05) in ovariectomized mice. CT significantly (P less than 0.05) increased mammary dry fat-free tissue weight from 2.89 +/- 0.41 mg (controls) to 3.78 +/- 0.37 mg (CT-treated) and from 4.03 +/- 0.59 mg (E/P-treated) to 5.42 +/- 0.91 mg (E/P + CT). Similarly, CT treatment increased mammary DNA from 138.7 +/- 11.7 micrograms (controls) to 162.8 +/- 14.4 micrograms (CT) and from 178.5 +/- 12.6 to 233.9 +/- 28.0 micrograms in the presence of E/P (P less than 0.05). Furthermore, CT was found to be mammogenic in hypophysectomized mice treated with E (1.0 microgram/day), P (1.0 mg/day), deoxycorticosterone acetate (0.5 mg/day), T4 (0.2 microgram/ml drinking water), and glucose (50 mg/ml drinking water), i.e. mammary gland development scores were 1.5 +/- 0.1 in mice treated with the above regimen and 3.1 +/- 0.1 in mice treated with the above regimen plus CT for 14 days (P less than 0.05). These results provide clear evidence, heretofore unreported, that systemic CT treatment increases mammary gland development and growth in female mice. The mammogenic effects of CT are observed in intact female mice with or without exogenous E/P, in ovariectomized mice treated with E/P, and in hypophysectomized mice treated with E/P, deoxycortisone acetate, and T4. PMID- 4042968 TI - Imprinting of growth hormone secretion, body growth, and hepatic steroid metabolism by neonatal testosterone. AB - The influence of endogenous sex steroids and exogenous testosterone treatment on pulsatile GH secretion, body weight, longitudinal bone growth, and hepatic steroid metabolism was studied in male and female adult rats. Blood samples were obtained from the tip of the tail, and maximum and minimum GH levels were determined in individual rats to evaluate pulse heights and baseline levels. Longitudinal bone growth was measured using the intravital marker tetracycline, and hepatic steroid metabolism was evaluated by determining the enzyme activities of 16 alpha-hydroxylase and 5 alpha-reductase. Neonatal, but not prepubertal, gonadectomy of male rats suppressed maximum and mean plasma GH levels during adult life. The body weight and the rate of longitudinal bone growth were also decreased. Testosterone treatment neonatally reversed all of these effects. Neonatal gonadectomy of male rats also caused an elevation of minimum plasma GH levels, an effect, however, which was not reversed by testosterone replacement during neonatal life. Neonatally gonadectomized females treated with testosterone neonatally or during adult life increased their maximum and decreased their minimum GH levels. Their longitudinal bone growth was increased. The body weight of these rats was increased by neonatal, but not adult, testosterone treatment. There was no effect of neonatal ovariectomy on plasma GH levels in 3- to 4-month old female rats. However, neonatal ovariectomy did increase the maximum and mean plasma GH levels immediately postpubertally, suggesting that the effect of the ovaries on GH secretion differs among mature female rats of different ages. Prepubertal gonadectomy of male rats feminized their hepatic steroid metabolism by decreasing 16 alpha-hydroxylase and increasing 5 alpha-reductase activities. Neonatal gonadectomy caused an even more pronounced feminization, which was partly reversed in rats given testosterone replacement therapy neonatally. In neonatally gonadectomized female rats, treatment with testosterone during adult life increased 16 alpha-hydroxylase and decreased 5 alpha-reductase to levels seen in intact male rats. The present results indicate that neonatally secreted testicular androgens imprint the high amplitude pulses characteristic of GH secretion in adult male rats. Neonatal androgens also stimulate somatic growth and partially account for the masculinized hepatic steroid metabolism in the adult animal. It is proposed that imprinting of the GH secretory pattern contributes to the influence of neonatal testicular androgens on body growth and hepatic steroid-metabolizing enzymes. PMID- 4042969 TI - Effects of maternal hypothyroidism on the weight and thyroid hormone content of rat embryonic tissues, before and after onset of fetal thyroid function. AB - Embryonic tissues were obtained from normal (C) and thyroidectomized (T) rats between 9 and 21 days of pregnancy. We determined the number and weight, as well as the T4 and T3 contents (RIA), of 9- to 12-day-old embryotrophoblasts, of 13- to 21-day-old embryos and placentas, and of liver, lung, and brain from 20- and 21-day-old fetuses. T4 and T3 were found in all samples obtained from C dams, both before and after onset of fetal thyroid function. Despite low levels of both iodothyronines in fetal plasma near term, their concentrations in fetal brain and lung had reached half the maternal values. The T3/T4 ratio in fetal organs was the same, or higher, than in adult rats. Maternal thyroidectomy resulted in a marked decrease of the number and individual weights of viable conceptuses, throughout gestation. Fetal organ weights near term were also decreased, and changes were found in brain DNA and protein concentrations. T4 and T3 were undetectable in all embryotrophoblasts, embryos and placentas obtained from T dams before onset of fetal thyroid secretion. They were still markedly reduced in 21-day-old placentas. Total extrathyroidal contents of T3 and T4 in 20- and 21 day-old fetuses from T dams were also low as compared to those from normal mothers, but individual organs were not affected to the same degree. Thus concentrations were decreased in the carcass (whole embryo minus the trachea + thyroid + liver + lung + brain), but normal in the brain. These results show that maternal hypothyroidism is accompanied by thyroid hormone deficiency of the conceptus before the fetal thyroid functions. After this, alterations of T4 and T3 concentrations persist until term. Development is also delayed. Thus, adverse effects of maternal hypothyroidism may be due, at least in part, to the thyroid hormone deficiency of the embryonic tissues, and not only to the hypothyroid condition of the mother. PMID- 4042971 TI - Examination of the effects of epinephrine, norepinephrine, and dopamine on aldosterone production in bovine glomerulosa cells in vitro. AB - This study was undertaken to explore the possibility that the neurogenic amines epinephrine and norepinephrine may influence aldosterone production in vitro and to examine again the previously reported inhibitory effect of dopamine on aldosterone production. This was accomplished using bovine glomerulosa cell suspensions and a highly specific RIA for aldosterone. Epinephrine and norepinephrine (10(-6) - 10(-10) M) had no significant effect on aldosterone production. Both basal and angiotensin II-stimulated aldosterone production were significantly inhibited by dopamine, 10(-4) M, P less than 0.05. Basal aldosterone production was unaffected by lower concentrations of dopamine whereas angiotensin II-stimulated aldosterone production was inhibited in a dose dependent manner that was significant to 10(-6) M dopamine (P less than 0.05). Pretreatment of glomerulosa cells with the dopamine antagonist metoclopramide impaired the inhibitory effect of dopamine on aldosterone production. This study supports the hypothesis that dopamine may be a significant inhibitor of aldosterone production in vivo. The other neurogenic amines studied, epinephrine and norepinephrine, had no significant effect on aldosterone production in vitro. PMID- 4042970 TI - Angiotensin II restoration of reflex adrenal medullary secretion to anephric dogs is physiologically dose dependent. AB - Acute nephrectomy seriously impairs hypovolemic adrenal epinephrine (E) release in the anesthetized dog. That systemically delivered angiotensin II totally restores E release to acutely anephric dogs is equally clear, but the dose response relationship of this angiotensin II effect is not known. Adrenal secretion rates and arterial plasma E, norepinephrine (NE), and dopamine levels were studied in nine groups of mongrel dogs (n = 5 in each group) under pentobarbital anesthesia: 1) resting animals; 2) hemorrhage (25 ml/kg); 3) hemorrhage after acute nephrectomy; 4-7) hemorrhage, acute nephrectomy, plus iv angiotensin II at a) 0.01 ng/kg X min, b) 0.10 ng/kg X min, c) 1.00 ng/kg X min, or d) 10.00 ng/kg X min; 8) no hemorrhage, acute nephrectomy, angiotensin II (10.00 ng/kg X min); and 9) hemorrhage, kidneys intact, iv angiotensin II (10.00 ng/kg X min). Arterial and adrenal blood were sampled during a baseline prehemorrhage period and 15, 30, 60, and 90 min after hemorrhage. We confirm blunting of reflex E release by acute nephrectomy in the anesthetized dog and show that angiotensin II restores E (P less than 0.01), NE (P less than 0.01), and dopamine (P less than 0.01) release in acutely anephric dogs. Aortic plasma E and NE were also restored to normal by angiotensin II (P less than 0.01 for each). Dogs with intact kidneys show a blunted hemorrhage response of arterial plasma E (P less than 0.01), NE (P less than 0.01), and DM (P less than 0.05) to our largest angiotensin II infusion rate (10 ng/kg X min). The study demonstrates that in acutely anephric conditions, angiotensin II support of reflex catecholamine release is sensitively dose dependent to physiological infusion rates of systemic angiotensin II and suggests further that this angiotensin II effect is restrained by the kidneys. PMID- 4042972 TI - Estrogen-stimulated deoxyribonucleic acid synthesis: a ratchet model for the prereplicative period. AB - Multiple injections of a short acting estrogen, 1,3,5(10)-estratriene-3,16 alpha diol (16 alpha-E2), have been used to analyze the lag or prereplicative period of approximately 12 h, which precedes the onset of estrogen-stimulated DNA synthesis. A single injection of 1.0 microgram 16 alpha-E2, which itself does not stimulate DNA synthesis, shortened by 3-4 h the lag period between subsequently administered estrogen and the initiation of DNA synthesis. This lag-shortening effect of 16 alpha-E2 was stable for 24 h, but had decayed by 36 h. One or two additional injections of 16 alpha-E2 given sequentially at 3-h intervals each further shortened the lag period but to a lesser extent than the first injection. The results indicate that estrogen induces the accumulation of relatively stable cell changes which are required for the onset of DNA synthesis. The prolonged estrogen requirement during the lag period is not truly discontinuous as previously suggested but rather can be satisfied by discontinuous pulses of estrogen in a ratchet-like fashion because of the stability of their effects. PMID- 4042973 TI - Coordinate regulation of the messenger ribonucleic acids encoding the alpha- and beta-subunits of human chorionic gonadotropin in HeLa cells and butyrate resistant variants. AB - Short term exposure of HeLa S3 cells to sodium butyrate induces accumulation of the mRNAs encoding both the alpha- and beta-subunits of hCG. Both mRNAs accumulate with the same kinetics and reach maximal levels with the same concentration of butyrate, suggesting that the levels of alpha and hCG beta mRNAs are coordinately regulated. In addition, induction of both mRNAs is tightly coupled with a similar increase in secreted levels of hCG subunit protein, further suggesting that regulation of CG biosynthesis in HeLa cells occurs before translation. To determine whether HeLa cells which have overcome the growth inhibitory properties of butyrate show uniformly high levels of alpha and hCG beta mRNAs, we isolated clonal variants by stepwise selection with increasing concentrations of butyrate. Of 69 isolated variants, at least 2 (AO and B2) display different patterns of CG gene expression. In AO cells, alpha-subunit mRNA was not detectable, while in B2 cells, the level of alpha-subunit mRNA was similar to that of wild-type HeLa S3 cells. Conversely, hCG beta mRNA levels in both variant cell lines approximated levels found in butyrate-treated HeLa S3 cultures, suggesting that the mRNAs for alpha and hCG beta are regulated independently. Analysis of genomic DNA by blot hybridization indicated that the alpha-subunit gene was present as a single unrearranged copy in HeLa S3 cells and in both variants, indicating that differences in alpha-subunit gene expression are not associated with major genomic alterations, but probably reflect more subtle changes. PMID- 4042974 TI - Autocrine stimulation by prolactin of hormone-responsive breast cancer growth in culture. AB - Evidence obtained in human breast cancer cell lines in culture suggests that estradiol stimulates the synthesis of secretory proteins which may, in turn, mediate its mitogenic effect. We questioned whether a similar mechanism could mediate the growth-promoting effect of PRL in the N-nitrosomethylurea-induced rat mammary tumor grown in soft agar, where PRL exerts a dose-dependent colony stimulating effect. Conditioned medium obtained from PRL-treated tumors, but not from control tumors, was found to exert a significant dose-dependent colony stimulating effect when added to N-nitrosomethylurea-induced mammary tumors plated in soft agar under serum-free medium conditions. The growth-promoting action of conditioned medium from PRL-treated tumors was abolished by pretreatment with heat, trypsin, and Concanavalin-A, suggesting the possible glycoprotein nature of the oPRL-induced growth factor(s). These results provide support for the novel hypothesis that estradiol and PRL may support the growth of hormone-responsive breast cancer through a similar mechanism. PMID- 4042975 TI - Fetal rat myoblasts release both rat somatomedin-C (SM-C)/insulin-like growth factor I (IGF I) and multiplication-stimulating activity in vitro: partial characterization and biological activity of myoblast-derived SM-C/IGF I. AB - The relative release of rat somatomedin-C (SM-C)/insulin-like growth factor I (IGF I) and multiplication-stimulating activity (MSA) immunoreactivity and bioactivity from isolated fetal rat myoblasts was assessed by a partial characterization of the SM peptides present in concentrated myoblast-conditioned culture medium (MCM). The SM bioactivity of MCM, measured by [3H]thymidine or [35S]sulfate uptake by fetal rat cartilage explants, eluted with an apparent size of 50-80K on Sephadex G-200 at pH 7.5, and was associated with SM-C/IGF I immunoreactivity. Chromatography of MCM on Bio-Gel P-10 or Sephadex G-75 at acidic pH resulted in a peak of SM bioactivity associated with both SM-C/IGF I and MSA immunoreactivity in the 6-9K region. SM-binding activity, measured by competition with activated charcoal for [125I]SM-C or MSA, eluted in the void volume. When these fractions were incubated with [125I]SM-C and chromatographed on Sephadex G-200 at neutral pH, a heterogeneous pattern of binding proteins was seen, with a major component of 50-80K. After chromatofocusing of proteins in the 6-9K region from Bio-Gel P-10, three peaks of SM bioactivity were recovered, each associated with SM-C immunoreactivity, with pI values of 8.5, 7.1, and 6.5. Although both the basic and neutral peaks enhanced [3H]thymidine uptake by growth restricted fetal rat myoblasts in vitro, only the bioactivity of the former could be blocked by incubation with a monoclonal antibody to human SM-C. Both human SM C/IGF I and MSA purified from Buffalo rat liver cell-conditioned medium enhanced thymidine incorporation by growth-restricted fetal rat myoblasts. The results suggest that unlike reports of other fetal rat tissues, fetal rat myoblasts released approximately equal amounts of rat SM-C/IGF I and MSA during culture. The myoblast-derived SM-C/IGF I was biologically active on the cell type of origin and may play a paracrine role in muscle development. PMID- 4042976 TI - Hypothalamo-pituitary regulation of cytochrome P-450(15) beta apoprotein levels in rat liver. AB - The regulation of the sexually differentiated steroid sulfate 15 beta hydroxylase, cytochrome P-450(15) beta of female rat liver has been investigated. Specific antibodies raised to isozyme P-450(15) beta were used with the Western blot technique to quantitate the specific levels of P-450(15) beta in liver microsomes. The method demonstrated that the levels of the protein are about 16 fold higher in female than in male microsomes and also showed that the specific microsomal content of P-450(15) beta is controlled by GH. Hypophysectomy of female animals resulted in a decrease of P-450(15) beta to male levels. Continuous infusion of human GH, mimicking the female pattern of GH secretion in intact male animals, caused an elevation of the P-450(15) beta level to that of the female. The same dose of human GH in hypophysectomized male or female animals raised the P-450(15) beta level 8-fold or 50% of that seen in normal females. Infusion of ovine PRL to intact male rats had no effect on P-450(15) beta levels, whereas infusion of rat GH caused a 4-fold increase. Thus, the regulation of P 450(15) beta by GH is mainly associated with the somatogenic properties of the hormone. Furthermore, sc injection of rat GH every 12 h, mimicking the male pattern of GH secretion, had no effect on P-450(15) beta levels, demonstrating the importance of the GH secretory pattern in regulation of the specific protein levels. Postpubertal castration of male animals did not influence the microsomal P-450(15) beta content, whereas neonatal castration led to a feminization of the P-450(15) beta content in the adult male rat. Administration of estradiol valerate to male animals caused complete feminization of P-450(15) beta levels, whereas administration of androgen to female animals caused a decrease to male levels. Before 21 days of age, the P-450(15) beta level was slightly higher in male than in female rats. At 35 days, however, the P-450(15) beta level in female rats had increased almost 100-fold, whereas the levels in males increased only slightly. These changes are concomitant with the development of the sexual differentiation of the GH secretory pattern, supporting the role of GH in P 450(15) beta regulation. In conclusion, isozyme P-450(15) beta is a GH-regulated enzyme specific for female rats. The low level of the protein in males is probably explained by neonatal androgenic programming of the GH secretory pattern. PMID- 4042977 TI - Skin is an active site for the inner ring monodeiodination of thyroxine to 3,3',5'-triiodothyronine. AB - T4 (0.26 microM) was incubated in 0.1 M phosphate buffer (pH 7.4) containing 10 mM EDTA with homogenates (3-5 mg protein) of various rat tissues and up to 400 mM dithiothreitol (DTT) for 1 h at 37 C; the rT3 generated was measured by RIA of ethanol extracts of the incubation mixture. Among the various tissues of the male rat, homogenates of skin and cerebral cortex were very active in the conversion of T4 to rT3; other tissues demonstrated little or no T4 5-monodeiodinating activity (MA). The tissue content of rT3 was also greatest in these two tissues. The MA in skin increased linearly with incubation period (up to 4 h) and with increasing concentration of protein (up to 5 mg), substrate (up to 10 microM) and DTT (up to 400 mM); its optimal pH was 7.4, and optimal temperature was 37 C. Its Km and maximum velocity approximated 0.29 microM and 9.6 pmol/h X mg protein, respectively, in the presence of 400 mM DTT. There was no appreciable difference in T4 to rT3 MA of skin from different parts of the body. The MA was most abundant in microsomes and least in cytosol. The MA was unaffected by propylthiouracil (up to 25 microM), methimazole (up to 100 microM), sodium salicylate (up to 80 microM), or 8-anilino-1-naphthalene sulfonic acid (up to 75 microM). Ipodate (up to 80 microM) weakly inhibited the MA. T3 and 3,5 diiodothyronine inhibited dermal T4 to rT3 MA in a dose-dependent manner; T3 was 3-12 times more potent than 3,5-diiodothyronine on a molar basis in different experiments. Treatment of euthyroid rats with 3,5-dimethyl-3'isopropylthyronine (45 micrograms/day, ip) for 3 or 5 days significantly increased dermal T4 to rT3 MA. Similar treatment of rats with T4 (100 micrograms/day, ip) or T3 (20 or 80 micrograms/day, ip) did not change with MA appreciably. Hypothyroidism markedly inhibited the MA, and fasting inhibited it modestly. Pregnancy was associated with marked reduction in the MA of skin in the mother [0.30 +/- 0.11 (+/- SE) vs. 7.2 +/- 2.2 ng/h X mg protein; P less than 0.02] and fetus (0.67 +/- 0.075; P less than 0.025).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 4042978 TI - Nuclear localization of unoccupied receptors for glucocorticoids, estrogens, and progesterone in GH3 cells. AB - We have previously shown that the unoccupied receptor for estrogen is not present in enucleated cells (cytoplasts) and probably is nuclear in cells that have been enucleated using cytochalasin B and centrifugation. We now demonstrate, using enucleation without cytochalasin, that the unoccupied receptors for glucocorticoids and progesterone also appear to be nuclear, and that enucleation without using cytochalasin results in the same distribution of estrogen receptor as that seen when this drug is used. Enucleated cells (cytoplasts) contained only 5-10% of the concentration of unoccupied receptors found in the whole cells. The unoccupied receptors for all three hormones were recovered instead in the nucleus containing cell fragments (nucleoplasts). The cytosolic marker lactate dehydrogenase was present in the cytoplasts at the same or higher concentration than in the whole cells or nucleoplasts. Cytoplasts were formed from approximately 90% of the cells. When the nucleoplasts were homogenized, the unoccupied receptors for all three hormones were extracted into the cytosol, as is usually seen in homogenized cells and tissues. These results are, therefore, consistent with the possibility that the unoccupied glucocorticoid and progesterone receptors, like the unoccupied estrogen receptor, are nuclear rather than cytoplasmic proteins. In addition, localization of these unfilled receptors does not appear to be an artifact of cytochalasin treatment. PMID- 4042979 TI - The effects of estrogen and progesterone in vivo on protein synthesis and secretion by cultured epithelial cells from sheep endometrium. AB - Ovariectomized ewes were treated with either nothing or implants of estrogen (E), progesterone (P), or E + P. Epithelial and stromal cells from caruncular and intercaruncular regions of sheep endometrium were dispersed by collagenase digestion and enriched by Ficoll gradient separation. Verification of cell types was by electron microscopy, keratin staining (epithelial cells), cell size, and appearance in culture. Epithelial cells were cultured under optimized conditions with [35S]methionine (S-met) and uptake of label by cells and its incorporation into cellular and secreted protein determined. Protein in the medium and lysed cells was analyzed by two-dimensional sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Cells from E-treated animals had higher S-met uptake and incorporation into proteins (cellular and secreted) than cells from ewes treated with nothing and P-treated animals. E effects were not significantly reduced in the presence of P. When secreted protein was expressed as a percent of total incorporated S-met, P treatment either alone or with E increased the proportion of labeled protein secreted by cells. There were no significant differences between caruncular and intercaruncular. Two-dimensional polyacrylamide-gel electrophoresis of secreted proteins showed one major glycoprotein (mol wt, 46,000, isoelectric point, 5.8-6.5) and four minor proteins induced by E + P greater than E, and five minor proteins inhibited by the steroids. Both induction and inhibition of cellular proteins were also apparent, though of lesser magnitude. Overall, whereas E treatment in vivo influenced the rate of incorporation of S-met into proteins by epithelial cells in vitro, P treatment increased the proportion of newly synthesized protein which was secreted. Steroids caused significant alterations in the individual proteins secreted by ovine endometrium. PMID- 4042980 TI - Escape from the sodium-retaining action of intrarenal angiotensins II and III in the conscious dog. AB - The maximum amounts of angiotensins II and III that were confined to the kidney during intrarenal arterial administration in conscious dogs were determined to be 2 and 12 pmol/kg X min, respectively. These doses were infused chronically intrarenally to uninephrectomized dogs. A significant reduction in urinary volume and excretion of sodium was observed at 24 h of the intrarenal peptide infusions. These excretory effects were more marked with angiotensin III than with angiotensin II. Escape from the antidiuretic and antinatriuretic effects of angiotensins II and III was observed after 24 h in spite of continuous administration of the peptides. To define the role of reduced intrarenal angiotensin concentration in the physiological phenomenon of escape from the sodium-retaining action of mineralocorticoids, angiotensin II or III at the above doses was administered intrarenally together with 11-deoxycorticosterone acetate. No delay in escape from the sodium-retaining effects of the mineralocorticoid was noted as a result of concurrent intrarenal angiotensin administration. In conclusion, both angiotensin II and angiotensin III have direct sodium- and volume-retaining effects on the kidney. These renal effects are abolished within 48 h, either due to tachyphylaxis to angiotensins or by other mechanisms overriding the actions of angiotensins. No association was demonstrated between suppression of the renin-angiotensin system and escape from mineralocorticoid induced sodium retention. PMID- 4042981 TI - Gas chromatography-mass spectrometry of androgens in equine ovarian follicles at ultrastructurally defined stages of development. Identification of 19 nortestosterone in follicular fluid. AB - Follicular fluid was obtained from equine follicles at different stages of development as determined by ultrastructural study. Gas chromatography-mass spectrometry associated with stable isotope dilution permitted the demonstration of high levels of 4-estrene-3,7-dione and 17 beta-hydroxy-4-estren-3-one, 17 beta hydroxy-4-estren-3-one levels often being about 10 times higher than those of testosterone. These findings suggest that in the mare ovary, an aromatizing pathway may proceed using these 19-norsteroids as intermediates. As a consequence of this high level of 19-norsteroids, testosterone content may be most often overestimated by RIA. RIA of steroids in follicular fluid should be validated by a reference technique based on gas chromatography-mass spectrometry, associated with stable isotope dilution. PMID- 4042982 TI - Dexamethasone stimulates osteogenesis in chick periosteum in vitro. AB - Folded periosteal explants derived from 16-day-old chick embryo calvariae differentiate and form bone when cultured for 6 days in chemically defined, hormone-supplemented medium or on plasma clots. We studied the effect of dexamethasone on generation of cells with osteoblastic phenotype in such cultures. Bone cell phenotype was evaluated by determination of alkaline phosphatase (AP) activity. Cellular proliferation was assessed by measuring ornithine decarboxylase (ODC) activity, [3H]thymidine uptake, and radioautography of cultures that had incorporated [3H]thymidine. Cultures were exposed to various medium concentrations of dexamethasone (10(-6) M, 10(-7) M, 10(-8) M) from the outset or from the second or fourth day of culture onwards. In cultures continuously exposed to dexamethasone and maintained in chemically defined media or on plasma clots, dexamethasone increased AP activity measured at day 6. This effect was maximal at 10(-7) M dexamethasone. Cultures exposed to dexamethasone after day 2 in culture also showed increased AP activity, but only in the cultures maintained on plasma clots. There was no stimulation of AP activity when dexamethasone was added at day 4 of culture with either medium, thus suggesting that the effect of glucocorticoids depends on the stage of differentiation of the cultures. In addition to AP stimulation, dexamethasone also stimulated ODC activity. Since ODC activity has been associated with mesenchymal cell proliferation, this suggested that dexamethasone stimulated the proliferation of similar cells in the cultured periostea. Measuring [3H]thymidine uptake in and performing autoradiography of control cultures and cultures treated with dexamethasone confirmed that stimulation of proliferation did occur and located this proliferation within the cell layer adjacent to the bone surface. These results demonstrate that dexamethasone stimulates in vitro osteogenesis, and that this effect appears to be mediated through stimulation of progenitor cell proliferation. In addition, our data indicate that factors in the clot medium modulate the responsiveness of the precursor cell population. PMID- 4042983 TI - Variations in the oligosaccharides on free and combined alpha-subunits of human choriogonadotropin in pregnancy. AB - The glycoprotein hormone hCG and a free alpha-subunit are secreted by trophoblastic cells during pregnancy. We have purified the alpha-subunit of hCG and the free alpha-subunit population from pregnancy urine. Dissociation of hCG with 10 M urea at 37 C, followed by chromatography on DEAE-Sephacel, resulted in separation of alpha- from beta-subunit, as hCG alpha does not bind to DEAE in the presence of urea, while beta-subunit does bind. Similar treatment of the free alpha population resulted in fractionation into two populations, a nonbinding fraction of free alpha and a population which was retained by DEAE in the presence of urea (free alpha 2). The three populations, hCG alpha, free alpha, and free alpha 2, were further purified by affinity chromatography using anti alpha antisera linked to Sepharose. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the preparations showed that hCG alpha consisted of a single component with an apparent mol wt of 22,000, while free alpha and free alpha 2 consisted of multiple components. Radioactive labeling of sialic acid by limited periodate oxidation and NaB[3H]4 reduction resulted in a higher specific activity for free alpha than for hCG alpha, suggesting that free alpha contains more sialic acid per immunoreactive molecule than does alpha dissociated from hCG. [3H]hCG alpha, but not 3H-labeled free alpha, was able to combine with native hCG beta-subunit. The oligosaccharide moieties were released from the different labeled subunits by alkaline hydrolysis and then compared with respect to Concanavalin A (ConA)-binding and DEAE-binding properties. Most of the oligosaccharides from dissociated hCG alpha bound to ConA-Sepharose (72%), while less material from free alpha (40%) and even less from free alpha 2 (25%) were capable of binding to ConA. DEAE chromatography of the oligosaccharides suggested that hCG alpha contained primarily monosialylated forms (greater than 60%), while free alpha and alpha 2 contained primarily (greater than 70%) di- and trisialylated forms. Thus, the ConA and DEAE binding data indicated that the oligosaccharide contents of free alpha and free alpha 2 were quite different from that of hCG alpha. These results also suggest that some of the oligosaccharide structures contained on hCG alpha and most of those on free alpha and free alpha 2 differ substantially from the structures that have been previously described. PMID- 4042984 TI - The postnatal ontogeny of rat uterine glands and age-related effects of 17 beta estradiol. AB - In the uterus of the newborn rat, only the luminal epithelium is differentiated. Differentiation of musculature and glandular epithelium occurs postnatally, the latter originating as invaginations of the luminal epithelium into the stroma. Using unambiguous criteria for quantification of uterine glands, we find that uterine glands first appear on postnatal day 9 after which the increase in the number of glands is rapid and synchronous, with approximately 4.4 glands per uterine section reached by day 15. Between days 15 and 35, the number of glands per uterine section varied in a cyclic manner with an amplitude of approximately one gland per uterine section and a period of 6-7 days. Although exogenous 17 beta-estradiol (E2) administered on postnatal days 1-5 induced slight premature gland genesis, the number of glands per uterine section was approximately 30% lower between days 15-26 compared to untreated animals. Administration of E2 during the period of normal gland genesis (days 10-14) induced a dose-related delay in the onset of appearance of glands. After this, gland genesis proceeded at a normal rate; however, the maximum levels reached were again generally below those observed in untreated controls. E2 administered after uterine glands were established (days 20-24) induced a small increase in gland number compared to controls. E2 also induced temporary hypertrophy, hyperplasia, and cellular degeneration in the luminal epithelium during each of the dosing periods without corresponding changes in the stroma or myometrium. These data demonstrate that uterine gland genesis occurs between postnatal days 9-15 and that exogenous estrogen can alter, in an age-specific manner, both uterine gland genesis and the number of glands per uterine section. PMID- 4042985 TI - Inhibition of rat uterine gland genesis by tamoxifen. AB - We have previously shown that rat uterine gland genesis occurs rapidly and synchronously between postnatal days 9-15. Exogenous estrogens either stimulate or inhibit gland genesis depending on dose and age at administration. We therefore examined the developmental effects of the triphenylethylene antiestrogen tamoxifen, which exhibits both estrogen agonist and antagonist properties, in the postnatal rat uterus. Tamoxifen administered sc in oil on postnatal days 1-5 or days 10-14 caused dose-related inhibition of uterine gland genesis which persisted to day 26 or day 60, respectively. Tamoxifen administered on postnatal days 20-24, which is after the age of normal gland genesis, did not alter the number of preexisting glands. A 24-h exposure to tamoxifen inhibited 17 beta-estradiol (E2)-induced ornithine decarboxylase (ODC) activity measured 6 h after E2 administration in 14-day-old rats. Treatment with tamoxifen before or during the period of gland genesis also reduced uterine responsiveness to a single dose of E2 as measured by both uterine weight gain (after a 24-h exposure on days 14, 19, 22, and 26) and the pattern of E2-induced ODC activity in 26-day old rats. Control rats respond to E2 with peaks of ODC activity at 6 and 18 h after administration. Treatment with tamoxifen on either postnatal days 1-5 or 10 14 reduced the 18-h peak to approximately half of controls but did not affect the 6-h E2-induced ODC peak. Analysis of both nuclear and translocatable cytosol estrogen receptor in uteri from 26-day-old rats indicate that neither the dissociation constant (KD) nor the number of binding sites was affected by tamoxifen treatment on postnatal days 1-5 or 10-14. PMID- 4042986 TI - Disturbed prolactin responses to dopamine-related substances in patients with acromegaly and hyperprolactinemia. AB - We undertook this study, because conflicting data were reported about the dopaminergic regulation of prolactin (PRL) secretion in patients with acromegaly and hyperprolactinemia. In order to clarify the dopaminergic regulation of PRL secretion in patients with acromegaly and hyperprolactinemia, the effects of nomifensine, a central dopamine agonist, FK 33-824, a centrally antidopaminergically acting agent, and domperidone, a peripheral dopamine antagonist, on plasma PRL in these patients were studied. The results were compared with those observed in normal subjects and hyperprolactinemic patients, with or without a pituitary tumor. Nomifensine did not lower the PRL levels and FK 33-824 did not raise the PRL levels in acromegalic patients. In hyperprolactinemic patients, nomifensine did not lower the PRL levels and FK 33 824 failed to raise the PRL levels. Domperidone did not increase PRL in about a third of acromegalic patients, while TRH increased PRL in the all normoprolactinemic acromegalic patients. These results suggest that in acromegalic patients there may be a disturbance in dopamine related neurotransmission and that such disorders also seem to be present in patients with hyperprolactinemia, with or without a pituitary tumor. PMID- 4042987 TI - Effect of colchicine on the depletion and replenishment of cytoplasmic glucocorticoid receptor in rat liver after administration of glucocorticoid. AB - Pretreatment of rats with colchicine (3 mg/kg body weight) modified the time course of depletion of the cytoplasmic binding sites for 3H-dexamethasone after administration of prednisolone (0.5 or 1.5 mg/kg body weight). Colchicine also decreased the rate of the cytoplasmic receptor replenishment which was confirmed by application of this drug after completion of the cytoplasmic receptor translocation to nuclei (30 min after prednisolone injection). Addition of colchicine to the incubation mixture for in vitro binding of 3H-dexamethasone labelled liver cytosol to isolated liver nuclei suspended in TKMS buffer (50 mM Tris-HCl, pH 7.5, 50 mM KCl, 5 mM MgCl2 and 250 mM sucrose) evoked no measurable changes in the rate of the nuclear binding. PMID- 4042988 TI - Development of enzyme-linked immunospecific assay (ELISA) for the detection of monoclonal antibody: application to detection of monoclonal anti-TBG. AB - An enzyme-linked immunospecific assay (ELISA) was developed to screen monoclonal antibody to human thyroxine-binding globulin (TBG). The assay is based on the absorption of TBG from human pooled serum by rabbit polyclonal anti-TBG antibody coated on a microtiter plate and subsequent binding of monoclonal antibody to the absorbed antigen. Monoclonal antibody which binds TBG can be detected by peroxidase labeled anti-mouse IgG. From the examination with two different rabbit polyclonal anti-TBG antibodies, it was demonstrated that both purified IgG fraction and whole serum could be used as coating materials. It was not necessary to use purified TBG to react with anti-TBG antibody coated on the microtiter plate. When eight commercially available microtiter ELISA plates were tested in the assay, only 3 gave satisfactory results. The sensitivity of the assay was comparable with that of the conventional immunoprecipitation method using 125I TBG and formalin fixed Staphylococcus aureus (Kowan strain) as an immunoabsorbent. The ELISA method could detect antibody activity in 0.032 microliter of medium obtained from a 3 day culture of confluent hybridoma cells. It is possible to store the antibody-antigen complexed microtiter plate for more than 2 weeks at 4 C. This makes possible rapid screening of monoclonal antibody. PMID- 4042990 TI - A case of Cushing's syndrome associated with possible adrenomedullary hyperplasia. AB - A 57-year-old male, who had been suffered from hypertension and diabetes mellitus for 10 years, was admitted to the hospital because of thirst, lassitude and muscle wasting. On admission, his urinary excretion of 17-OHCS and plasma cortisol levels were elevated without diurnal variations. Plasma ACTH levels were found to be very low with repeated determinations. Dexamethasone suppression test, 2 mg 4 times a day orally for 2 days, showed no changes in plasma cortisol levels and only a mild reduction in urinary 17-OHCS excretion. Estimation of urinary catecholamines showed an increase only in norepinephrine. Abdominal computerized tomography and radionuclide scanning of adrenal glands with 131I adosterol demonstrated a well-defined adrenal mass in the left side without apparent changes in the right side. 131I-metaiodobenzylguanidine scintigraphy was negative. At surgery, his left adrenal medulla was found to be hypertrophic in addition to the cortical tumor. The left adrenal gland was also removed. After surgery, excretion of urinary catecholamines fell to nearly the normal range and he was discharged without insulin and antihypertensive drugs. Microscopically, the cortical tumor is an adenoma consisting of lipid laden cells and eosinophilic compact cells. Medullary cells were distinctly hyperplastic in appearance and many of the cells were extensively vacuolated, suggesting an active functional status. The present report describes a patient with Cushing's syndrome who showed increased urinary catecholamine excretion due to the possible coexistence of adrenal medullary hyperplasia. As far as we know, this is the first case of Cushing's syndrome with this abnormality. PMID- 4042989 TI - A malignant pheochromocytoma with ileus, polyuria and hypercalcemia: a case of recurrence 17 years after the initial operation. AB - A case of malignant pheochromocytoma, with a recurrence 17 years after the initial diagnosis of benign pheochromocytoma, was presented. The autopsy revealed multiple metastases of pheochromocytoma to the bone marrow of the thoracic and lumbar vertebrae. Of particular note is the fact that the patient was associated with paralytic ileus, polyuria and hypercalcemia and that he died of hypercalcemia crisis. Cases like this appear to be very rare. PMID- 4042991 TI - Congenital iodide organification defect accompanied by a large nodular goiter: a case report. AB - A girl who had a nontoxic diffuse goiter with a congenital organification defect of iodide was first seen at the age of 8 years, and since then she has been followed up for a long period. The nodularity of the thyroid gland had gradually progressed, because of intermittent failure of ingestion of thyroid hormone preparation which was followed by excess TSH secretion. 18 years later, a nodular goiter developed and the patient underwent subtotal thyroidectomy. In order to prevent the development of nodular change in the thyroid gland in this disorder, supplemental thyroid hormone medication should be started as soon as the diagnosis is confirmed, and the therapy should be carried out regularly. PMID- 4042992 TI - Twenty-four hour secretory pattern of thyroid-stimulating hormone in hyperprolactinemic women with pituitary microadenoma. AB - In order to determine whether endogenous dopaminergic tone has any role in the diurnal variation in TSH secretion, the 24-h secretory pattern of TSH and the TSH response to a dopamine antagonist, metoclopramide (MCP), were evaluated in normal women (n = 4) and in hyperprolactinemic-amenorrheic women with pituitary microadenoma (n = 6). TSH concentrations expressed as percent deviation from the 24-h mean significantly differed with respect to time of day in normal women and hyperprolactinemic women. They were significantly higher during the night (2000 0700 h) than during the daytime (0800-1900 h). Whereas MCP administration induced no significant changes in serum TSH levels in normal women, it significantly increased serum TSH levels in hyperprolactinemic women. Thus, the diurnal variation in TSH secretion was demonstrated in hyperprolactinemic women with pituitary microadenoma in the face of an increased dopaminergic inhibition of TSH secretion. The present study did not provide evidence that the diurnal pattern of TSH secretion is related to the endogenous dopaminergic tone. PMID- 4042994 TI - Clinical usefulness of the (chloride-90)/phosphate ratio for distinguishing primary hyperparathyroidism from hypercalcemia due to other causes. AB - In order to obtain a good separation line between patients with primary hyperparathyroidism (1 degree HPT) and those with non-parathyroidal hypercalcemia (NPHC), serum chloride (Cl) and phosphate (P) concentrations were analyzed. Ninety-nine per cent of the patients with 1 degree HPT had a Cl/P ratio greater than or equal to 33, but 29% of patients with NPHC were also included in this range. When the (Cl-90)/P ratio was used to separate into two groups, 98% of the patients with 1 degree HPT had a ratio greater than or equal to 5.0, and 94% of the patients with NPHC had a ratio less than 5.0. From these results, while high sensitivity was achieved both with the Cl/P and (Cl-90)/P ratios, the (Cl-90)/P ratio provided higher specificity. Therefore we conclude that the (Cl-90)/P ratio was excellent in distinguishing 1 degree HPT from other types of hypercalcemia. PMID- 4042993 TI - Properties of binding of partially purified glucocorticoid receptor from rat liver with glucocorticoids of different biopotencies. AB - To elucidate the relationship between binding parameters and biopotencies of glucocorticoids, we partially purified the receptor from the liver cytosol of rats in a dexamethasone-bound and unactivated form by precipitation with protamine sulfate, gel filtration and DEAE-cellulose chromatography (approximately 100-fold) and examined the interaction of the preparation with 3 glucocorticoids of different biopotencies (dexamethasone; Dex, corticosterone; Cort and prednisolone; Pred). The partially purified receptor (PPR) was stable at -20 degrees C for at least 2 months in the presence of bovine serum albumin, glycerol, molybdate and dithiothreitol. Treatment of the PPR with p hydroxymercuribenzoate liberated the ligands and the treated PPR reassociated 3H glucocorticoids efficiently following the addition of dithiothreitol. The reassociated PPR was bound to the DNA-cellulose after a brief heating. Metabolic activity on ligands and inactivation of the binding sites in the PPR were insignificant under the conditions used. Kd's were approximately 0.9, approximately 3 and approximately 6 nM for Dex, Cort and Pred, respectively (at 0 degree C). Relative binding affinity of ligands to the PPR which was estimated by competitions was higher in the order of triamcinolone acetonide greater than Dex greater than Cort greater than Pred greater than progesterone greater than cortexolone. Association of Dex and Cort was relatively rapid and significantly accelerated by raising the incubation temperature, while the association of Pred was slower and effects of the temperature was moderate. The rate of dissociations was also varied with ligands. The rate of dissociation of Dex was the lowest among the 3 ligands and was elevated by raising the temperature. Because the effect of temperature was more pronounced in the dissociation than in the association, apparent Ka's decreased at higher temperature. Thermodynamic examinations of glucocorticoid binding in the PPR revealed that the binding reaction proceeds at a higher rate in the order of Dex greater than Cort greater than Pred. Because the relative biopotencies of these 3 glucocorticoids in vivo is higher in the order of Dex greater than Pred greater than Cort, from the results obtained in the present study, it appears that biopotency of glucocorticoids in vivo does not correlate with the affinity of the binding to the receptor estimated in vitro. PMID- 4042995 TI - Diurnal variation in carbohydrate tolerance to mixed meal in insulin-dependent diabetic adolescents during continuous intravenous insulin infusion (CIVII). PMID- 4042996 TI - Growth hormone and prolactin levels in the course of metoclopramide test in headache patients. PMID- 4042997 TI - [Circadian rhythm of growth hormone secretion in Turner's syndrome]. PMID- 4042998 TI - [Effect of subchronic cadmium chloride, lead acetate and zinc chloride poisoning on the thyroid gland in rabbits receiving adequate amounts of iodine]. PMID- 4042999 TI - [Scintigraphically detected "cold" nodules in patients of the Thyroid Disease Clinic in Gdansk--a clinical and histomorphological analysis]. PMID- 4043000 TI - Normal coordinate analysis of 5'-dGMP and its deuterated derivatives. A calculated approach to designate the guanine-residue vibration modes in B and Z forms of DNA. AB - By calculations based on the Wilson GF-method and using a valence force field, the vibration modes of 5'-dGMP have been assigned. Good agreement was obtained between the calculated and experimental results corresponding to the Raman and infrared spectra of 5'-dGMP. The calculations can also predict the displacement of infrared bands observed upon selective deuteration on C8 and simultaneously on the C8, N1 and N2 atoms of the guanine ring. In order to preserve the harmonic approximation of the potential field, the redundancy between the internal coordinates is entirely removed using a B X B matrix-product diagonalization procedure. In this treatment the local symmetry of different constituents of the molecule is taken into consideration, thus avoiding extensive linear combinations of internal coordinates. The extension of these calculations to the guanosine moiety involved in the double helix structures of DNAs allowed us to reproduce a certain number of the characteristic guanine vibration modes altered by the B--- Z transitions of poly(dG-dC).poly(dG-dC) and d(CG)3.d(CG)3. PMID- 4043001 TI - Determination of the second order doppler shift of iron in myoglobin by Mossbauer spectroscopy. AB - We have performed Mossbauer absorption experiments on a sample of deoxygenated myoglobin crystals from 5 K to 280 K. With two series of measurements, one with the source and sample at the same temperature and the other with the source always at 298 K, we are able to extract information from the second-order Doppler effect in the sample. Simple models consistent with a description of myoglobin with low lying electronic states which are thermally populated above 40 K indicate that the Debye temperature of myoglobin is 220 K, in agreement with measurements using the Lamb-Mossbauer factor. The second-order Doppler effect is proportional to the square of the velocity of the motion. We are unable to see any indication of protein specific motion from the second-order Doppler effect, thereby indicating that protein specific motions are relatively slow. PMID- 4043002 TI - On the dielectrically observable consequences of the diffusional motions of lipids and proteins in membranes. 1. Theory and overview. AB - A system consisting of any array of cylindrical, polytopic membrane proteins (or protein complexes) possessed of a permanent dipole moment and immersed in a closed, spherical phospholipid bilayer sheet is considered. It is assumed that rotation of the protein (complex) in a plane normal to the membrane, if occurring, is restricted by viscous drag alone. Lateral diffusion is assumed either to be free and random or to be partially constrained by barriers of an unspecified nature. The dielectric relaxation times calculated for membrane protein rotation in a suspension of vesicles of the above type are much longer than those observed with globular proteins in aqueous solution, and fall in the mid-to-high audio frequency range. If the long range lateral diffusion of (charged) membrane protein complexes is essentially unrestricted, as in the "fluid mosaic" membrane model, dielectric relaxation times for lateral motions will lie, except in the case of the very smallest vesicles, in the sub-audio (ELF) range. If, in contrast, the lateral diffusion of membrane protein complexes is partially restricted by "barriers" or "long-range" interactions (of unspecified nature), significant dielectric dispersions may be expected in both audio- and radio-frequency ranges, the critical (characteristic) frequencies depending upon the average distance moved before a barrier is encountered. Similar analyses are given for rotational and translational motions of phospholipids. At very low frequencies, a dispersion due to vesicle orientation might in principle also be observed; the dielectrically observable extent of this rotation will depend, inter alia, upon the charge mobility and disposition of the membrane protein complexes, as well as, of course, on the viscosity of the aqueous phase. The role of electroosmotic interactions between double layer ions (and water dipoles) and proteins raised above the membrane surface is considered. In some cases, it seems likely that such interactions serve to raise the dielectric increment, relative to that which might otherwise have been expected, of dispersions due to protein motions in membranes. Depending upon the tortuosity of the ion-relaxation pathways, such a relaxation mechanism might lead to almost any characteristic frequency, and, even in the absence of protein/lipid motions, would cause dielectric spectra to be much broader than one might expect from a simple, macroscopic treatment. PMID- 4043003 TI - Incorporation of the antimicrobial protein seminalplasmin into lipid bilayer membranes. AB - The interaction between seminalplasmin, an antimicrobial protein from bull semen, and lipid bilayers has been investigated. The fluorescence of the single tryptophan residue of the protein was measured. In the presence of phosphatidylcholine or phosphatidic acid bilayer vesicles the fluorescence maximum was shifted to shorter wavelengths, indicating transfer of the tryptophan to a more apolar environment. Circular dichroism spectra show an increased alpha helical content for the protein in the presence of lipid. Quenching experiments clearly show the incorporation of the protein with the tryptophan localized near the bilayer surface. The shift of the tryptophan fluorescence emission was used to monitor the lipid phase transition in phosphatidylcholine membranes. PMID- 4043004 TI - Ultrasonic absorption studies of protein-buffer interactions. Determination of equilibrium parameters of titratable groups. AB - The acoustic absorption of protein solutions in the presence of phosphate and other buffering ions has been studied in the physiological pH range. Buffers containing hydroxyl residues as titratable groups cause a pronounced increase of protein sound absorption, which is attributed to relaxation processes of proton transfer reactions between buffer ions and accessible imidazole and alpha-amino groups of the protein surface. Amino group based buffers like Good's buffers do not induce additional sound absorption. Measurement of the ultrasonic absorption as a function of pH and of buffer concentration, and corresponding parameter fitting of the equation describing proton transfer relaxation processes has been used to evaluate equilibrium parameters. For the imidazole group of the amino acid histidine a pK value of 6.22 and for the imidazole group of the protein lysozyme a pK value of 5.71 have been determined. In hemoglobin the ligand-linked pK changes have been monitored by recording ultrasonic titration curves. PMID- 4043005 TI - Liposomal cholesterol binding to steroid-free cytochrome P450scc: effects of fatty acyl and head groups in phospholipids. AB - The effects of fatty acyl substituents and head groups of phospholipids on the liposomal cholesterol transfer to steroid-free cytochrome P450scc were examined as a model system for ACTH-enhanced availability of cholesterol to the cytochrome in the inner membrane of adrenal cortex mitochondria. It was implicated that using a variety of saturated and unsaturated phospholipids fatty acyl groups play an important role in the transfer reaction. PMID- 4043006 TI - Injury to the isolated, perfused lung by exposure in vitro to monocrotaline pyrrole. AB - Monocrotaline pyrrole (MCTP) is a reactive metabolite of the pyrrolizidine alkaloid monocrotaline. It causes pulmonary lesions associated with pulmonary hypertension and right ventricular hypertrophy. Conditions of exposure to MCTP that result in early lung injury were examined in isolated rat lungs perfused with buffered medium containing 4% bovine serum albumin. When a high, acutely lethal dose (8.1 mg) of chemically synthesized MCTP was added to the 50-ml perfusion medium reservoir, no effects on the perfused lung occurred. However, when the same quantity of MCTP was injected directly into the pulmonary arterial (PA) cannula, the lungs accumulated considerable fluid within 1 h, and this was accompanied by elevated perfusion pressure and elevated lactate dehydrogenase (LDH) activity in the perfusion medium. A lower dose (1.2 mg) of MCTP that is pulmonary hypertensive in vivo also produced edema and elevated perfusion pressure when injected into the PA cannula. Removal of perfused 5 hydroxytryptamine, a function of pulmonary endothelium, was unaltered compared to vehicle-treated control lungs, as was perfusate LDH activity. These results indicate that injury to isolated lungs occurs soon after direct exposure to MCTP, even at a moderate dose that produces primarily delayed effects in vivo. PMID- 4043007 TI - Epithelial-mesenchymal interactions in postnatal rat lung growth. AB - Epithelial-mesenchymal interactions have been implicated in epithelial cell differentiation in fetal lung. The role of such intercellular communication during postnatal lung growth is now evaluated to correlate intercellular contacts with cell division and with biochemical function of epithelial and interstitial cells. Sexed newborn rats, killed at frequent intervals to 8 weeks, received 3H thymidine 1 h before death. A period of rapid cell proliferation between 3 and 10 days involved a five-fold increase in labeling index of both interstitial and type 2 epithelial cells. Hydroxyproline levels increased rapidly as interstitial cell division slowed, and epithelial growth was associated with elevated levels of disaturated phosphatidylcholine. Compared to the time of birth when epithelial cell division was slow, continuous basement membrane (BM) was more frequently found beneath type 2 cells during the postnatal proliferative phase, and fewer foot processes (FP) penetrated the BM; type 1 cells had few FP and uninterrupted BM. The number of intercellular contacts between type 2 cells and interstitial cells, one per two epithelial cell profiles at birth, decreased rapidly during the postnatal proliferative phase. There was a subsequent increase between 2 and 4 weeks that may reflect postmitotic epithelial differentiation. These observations support the hypothesis that transfer of mesenchymal factors may be important in the control of pulmonary epithelial growth and differentiation. The low incidence of cell-cell contacts seen after 4 weeks, one per five epithelial cell profiles, may reflect base levels of communication necessary to retain type 2 cell function in a resting cell population. PMID- 4043008 TI - Epidemiology of epilepsy in urban areas of the People's Republic of China. AB - To determine the prevalence of major neurologic disorders, a door-to-door survey was conducted in six cities of the People's Republic of China during 1983 in a well-defined population of 63,195. The survey included a complete census and a screening interview together with an examination having high sensitivity for detecting individuals with frequently occurring neurologic disorders, including epilepsy. All individuals with responses or findings suggesting neurologic disease were examined by senior neurologists using standardized diagnostic criteria. There was 100% cooperation among the study subjects. Two hundred eighty nine individuals alive on prevalence day (January 1, 1983) were identified as having epilepsy, yielding a lifetime age-adjusted (to the 1960 U.S. population) point prevalence ratio of 4.4/1,000. There were 16 people who developed epilepsy in the sample population during 1982, providing an age-adjusted incidence rate of 35/100,000 per year. The most frequent type identified was generalized convulsive seizures. Brain injury, intracranial infection, and cerebrovascular disease, in that order, were the leading putative causes of epilepsy. PMID- 4043009 TI - Neuropsychological abilities of children with epilepsy. AB - One hundred eighteen epileptic children, aged 6-15 years, underwent detailed neuropsychological testing including the Wechsler Intelligence Scale for Children Revised and the age-appropriate Halstead-Reitan battery. Eight had classical absence seizures only, eight had classic absence seizures and generalized tonic clonic seizures, 30 had generalized tonic-clonic seizures only, 31 had partial seizures only, 20 had partial seizures and generalized seizures, 15 had atypical absence seizures, and five had minor motor seizures. A control group of 100 children without seizures, matched to the general population for intelligence and matched to the seizure cases for age, underwent identical testing. The Wechsler full-scale intelligence quotient (FSIQ) of cases was significantly (p = 0.01) lower than that of controls and was related to seizure type. Children with minor motor or atypical absence seizures had the lowest average FSIQ (70 and 74, respectively). All seizure types were associated with below-control intelligence except classic absence only. Intelligence was also correlated with degree of seizure control. A highly significant inverse correlation between years with seizures and intelligence was found (p less than 0.0001). A rating of neuropsychological impairment, derived from all measures of brain function, was assigned to each child. Epileptic children had significantly more impairment than controls (p less than 0.0001). Children with seizures had been placed in special education or had repeated a grade in school almost twice as frequently as controls (p less than 0.001). Even though often placed in a class of younger children, their academic achievement was behind grade placement more often than in controls.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4043010 TI - The axial spasm--the predominant type of drop seizure in patients with secondary generalized epilepsy. AB - In 45 patients suffering from secondary generalized epilepsy, we have recorded 239 drop seizures both by radio-telemetered EEG/split-screen video taping and polygraphically. Twenty of these patients had pure tonic drop seizures. Nine patients each had myoclonic-atonic or pure atonic seizures, whereas seven had slow falls that occurred during gradually developing tonic or akinetic seizures. We term the pure tonic drop seizure "axial spasm." It consists of a uniform pattern of movement lasting from 0.5 to 0.8 s and leading to a specific bearing characterized by a moderate flexion of the hips, the upper trunk, and the head. The arms are almost always involved being abducted, elevated and in a semiflexed position. A fall is provoked by the rapidity and violence of the flexion in the hips. The spasms can occur independently (pure axial spasm) or in connection with other seizure manifestations (combined axial spasm). In pure spasms, no disturbance of consciousness and no significant EEG changes--apart from a slight attentuation--are seen. In the combined axial spasms, distinct epileptic phenomena, in close connection with the axial spasms, can be observed, appearing either in the postspasm phase or in both the pre- and the afterphases. The prephase consists always of an absence and spike-and-wave activity. The onset of the spasm coincides with the last generalized spike, which is followed by a biphasic high-voltage slow wave. In the afterphases, various seizure patterns can be seen; quite characteristic are arrest states during which the patients are completely immobile and take up a postural-like or athetoid position. Almost as frequent are absences or absence-like states and tonic seizures. The afterphase can be compounded by two or three of these seizure patterns, the most common sequence of events in these cases being tonic--arrest state--absence. From the clinical and neurophysiological points of view, axial spasms can be regarded as a more mature form of infantile spasms. Clinical and experimental findings suppose a brainstem origin. PMID- 4043011 TI - Relative bioavailability of rectally administered carbamazepine suspension in humans. AB - The relative bioavailability of an investigational carbamazepine suspension was studied following rectal administration in human volunteers. Carbamazepine, in doses of approximately 6 mg/kg, was given to nine men. The routes of administration were oral tablet, oral suspension, and rectal suspension. There was no significant difference (p greater than 0.05) in total absorption, maximum serum concentration, and time to achieve maximum serum concentration between the orally-administered tablet and the rectally administered suspension. Orally administered suspension was absorbed more quickly and completely. All volunteers complained of a strong defecatory urge after the suspension was given rectally. The slow absorption after rectal administration precludes the use of this route in status epilepticus; however, it may be a satisfactory alternative for maintenance therapy when administration by the oral route is not possible. PMID- 4043012 TI - Antiepileptic therapy, folate deficiency, and psychiatric morbidity: a general practice survey. AB - The effect of anticonvulsant drugs on folate metabolism and mental symptoms has been investigated extensively in hospital-based studies, but never before in the community or general practice setting. Blood count, serum vitamin B12, red blood cell (RBC), and serum folate were measured in a sample of 82 adult epileptic patients drawn from 5 group practices (14 general practitioners) in southeast London. All patients were receiving antiepileptic medication at the time of examination and were interviewed with a standardized measure of psychopathology. Serum folate values below the lower limit of the normal range (3-15 micrograms/L) were obtained in 9 (10.9%) subjects, and in 50 (60.9%) patients, serum folate concentrations were less than the mean (6.02 micrograms/L) for the whole sample. Macrocytosis was detected in 20 (24.3%) patients. RBC and serum folate levels were significantly correlated with one another, but not with vitamin B12 concentrations. Levels of RBC and serum folate were significantly lower in patients on polytherapy (n = 40) than in those on monotherapy (n = 42); the folate concentrations were also significantly lower in the group with psychiatric morbidity. The association between folate deficiency and affective morbidity was demonstrated for depression but not for anxiety. There was no relationship between serum vitamin B12 and psychiatric disturbance. These findings are discussed in the light of relevant literature regarding the mechanism of action of anticonvulsant drugs in folate depletion and the neuropsychiatric sequelae. PMID- 4043013 TI - Neuron density in the molecular layer of the frontal cortex in primary generalized epilepsy. AB - Developmental disturbance of the brain as a factor in the causation of epilepsies has been suspected for a long time. An increase of nerve cells in the stratum moleculare, which is qualitatively observed in primary generalized epilepsy, is thought to be an indicator for slight maldevelopment. In this morphometric study, the neuron density of layer I in the frontal lobe in primary generalized epilepsy is measured. Compared with age-matched controls, the neuron density in primary generalized epilepsy is significantly increased. Thus, neuron density could be a significant index for the disturbance of regional maturation of the cortex. PMID- 4043014 TI - A new centrifugal filtration device for free drug separation. AB - A new centrifugal membrane filtration device (Syva Corporation) has been evaluated to determine its capabilities for separation of free phenytoin for analysis. The device is a test tube-size cylinder with two compartments separated by the membrane. In serum samples from 70 patients at the Hospital of the University of Pennsylvania, free phenytoin was prepared by the new device and by equilibrium dialysis. Levels were assayed by gas chromatography and enzyme immunoassay with good agreement at all phenytoin levels. Although pH has a significant effect on the binding of some drugs to serum proteins, phenytoin binding increased to only a small extent as pH was increased from 7.0 to 7.8 (85 88.5% bound). Centrifugal filtration with this device is a reliable, fast, and easy way to prepare free drug from serum and does not include the dilution artifact inherent in equilibrium dialysis. PMID- 4043015 TI - Reduction of rat hippocampal calcium-binding protein following commissural, amygdala, septal, perforant path, and olfactory bulb kindling. AB - The calcium-binding protein (CaBP) content of the hippocampal formation was determined by radioimmunoassay in control and kindled rats. Kindling of a number of different sites resulted in a reduction in the CaBP content of the hippocampal formation, which was shown immunohistochemically to be restricted to the dentate granule cells and their processes. The maximum decline in CaBP varied with the different kindling sites: perforant path, 33%; commissural path, 32%; septum, 30%; amygdala, 18%; and olfactory bulbs, 15%. There were no changes in the CaBP content of the stimulated areas themselves. In cases where the kindling stimulus was delivered unilaterally (perforant path and amygdala), the maximum decrease in hippocampal CaBP was observed ipsilateral to the site of stimulation when the criterion for full kindling was established (six consecutive stage 5 motor seizures). Further kindling trials were required to produce a similar magnitude decrease in the CaBP content of the contralateral hippocampus. These observations are discussed both in relation to the possible role of CaBP in the establishment of a seizure response to kindling and also as a potential compensatory mechanism that may serve to overcome the epileptogenic effects of kindling. PMID- 4043016 TI - Experimental febrile convulsions in epileptic chickens: the anticonvulsant effect of elevated gamma-aminobutyric acid concentrations. AB - The high seizure susceptibility in epileptic chickens is due to an autosomal recessive mutation. In 3-day-old chicks homozygous for the epilepsy gene (epileptics), elevation of body temperature using microwave diathermy evoked an initial febrile seizure resembling the clonic seizures evoked in epileptic chicks by photic stimulation. After complete recovery, this was followed by a clonic tonic seizure. In nonepileptic heterozygote hatchmates (carriers) of the same age, only the latter seizure pattern was observed. In 16- to 17-day-old chicks of either phenotype, both seizure patterns were observed during hyperthermia. In all cases, the temperature at which seizures occurred was significantly lower in epileptic than in nonepileptic chicks, indicating a lower threshold for febrile seizures when there is an inherited predisposition to convulse. The occurrence of seizures was dependent on the body temperature and not on the rate of rise of temperature. Elevation of the brain gamma-aminobutyric acid (GABA) concentrations by administration of the GABA transaminase inhibitor gamma-vinyl GABA reduced the incidence of the initial febrile seizures and increased the latency in those birds that were not fully protected. PMID- 4043017 TI - Kindling epileptogenesis in orbital and mesial frontal cortical areas of subhuman primates. AB - Despite ready bilateralization of ictal and interictal EEG discharge throughout cortical kindling, the rate of convulsive seizure development was slow at both orbital and mesial frontal sites, even in the epileptic baboon. However, convulsive generalization occurred swiftly from the mesial frontal cortical (MF) sites once conjugate head, eye, and body adversion developed in the three primate species examined. Only epileptic baboons developed Stage 5 bisymmetrical and bisynchronous convulsion. Stimulation of the contralateral homotopic mesial cortical site readily produced afterdischarge that remained localized and convulsive seizure development did not occur. The findings suggest that (a) the frontal lobe plays an important role in the generation of nonconvulsive seizures, (b) the frontorolandic cortex plays a unique role in convulsive seizure generalization, (c) the role of the intrinsic (genetic) factor is significant in determining the quality of the kindled seizure, and (d) the development of focal epileptogenesis at one MF site interferes with clinical seizure development at the "mirror focus." Our findings underscore (a) the necessity of the conceptual differentiation between the EEG mirror focus and the epileptogenic focus capable of generating clinical seizures and (b) the importance of dissecting interictal behavior reflecting a "continuous disorder of neuronal function," which may cause symptoms other than seizures. PMID- 4043018 TI - Is adenosine an endogenous anticonvulsant? AB - The anticonvulsant properties of adenosine were tested pharmacologically on amygdala-kindled seizure activity in rats. The adenosine analogue 2 chloroadenosine and the adenosine uptake blocker papaverine both increased the latency to behavioral clonus as well as reduced the duration and severity of the clonic motor convulsion. Both drugs, however, failed to alter the postkindling afterdischarge (AD) threshold. Theophylline, an adenosine antagonist, had the opposite effects, prolonging the AD and motor seizure durations and facilitating partially kindled seizures, but again not altering the prekindling or postkindling AD thresholds of amygdala-elicited seizures. In contrast, carbamazepine raised AD thresholds, suggesting that it does not produce its anticonvulsant effects through adenosine systems. Since endogenous adenosine can impede seizure spread and seizure continuation, but does not affect seizure initiation from the amygdala, perhaps endogenous adenosine has the special property of being brought into play as an anticonvulsant only by the seizure itself. PMID- 4043019 TI - Neuronal firing pattern following amygdaloid kindling in unrestrained rats. AB - Chronic recordings of amygdaloid neurons were performed on freely moving rats following kindling. Satisfactory recordings were obtained from 22 amygdaloid neurons of the contralateral amygdala before, during, and after unilateral kindling. Kindling stimulations were given once per hour. Seven cells disappeared during kindling. Seven cells were recorded during the full course of kindling. These units showed (a) an increase in spontaneous firing, (b) a development of high-frequency bursts (the peak interval of the interval histogram decreased from 18 to 2 ms), and (c) high-frequency firings during spontaneous activity that were similar to the firings recording during afterdischarge. PMID- 4043020 TI - HGPRT- mutants of V79 cells that revert specifically by base pair substitution and frameshift mutations. AB - In order to determine the mutagenic specificity of mutagenic and carcinogenic agents in mammalian cells, a reversion system capable of distinguishing between frameshift mutations and various kinds of base pair substitutions would be useful. We report here a method for the isolation and characterization of HGPRT- Chinese hamster V79 cell mutants that might form the basis for such a system. Two mutants of different specificity have been partially characterized. DEW-1, isolated following N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) treatment, is revertible by the base pair substitution mutagens MNNG and ethyl methanesulfonate (EMS), but not by frameshift mutagens. DSW-3, isolated following ICR-191 treatment, is specifically reverted by frameshift mutagens, but not by EMS or MNNG. With the further characterization of these and other mutants, it should be feasible to determine not only whether an agent is mutagenic in V79 cells, but also to determine the type(s) of mutation(s) it produces. PMID- 4043021 TI - Induction of sister chromatid exchanges by coal dust and tobacco snuff extracts in human peripheral lymphocytes. AB - The organic solvent extracts of sub-bituminous coal dust and tobacco snuff, both together and separately, were tested for the induction of sister chromatid exchanges (SCEs) in human peripheral lymphocytes. The results indicate that these extracts induced SCEs, and that when tested together synergistically induced SCEs in two of three donors. Studies with the organic solvent extracts of all five ranks of coal indicate that the extracts of bituminous, lignite, and peat, but not anthracite, induced SCEs. Similar experiments conducted with water extracts show that bituminous, lignite, and peat, but not sub-bituminous extracts, induced SCEs, and that anthracite was equivocal. To determine whether individuals differed in their SCE responses to coal dust extracts, lymphocytes from five donors were tested with organic solvent extracts of bituminous and sub-bituminous coal. An analysis of variance indicates that the SCE response was significantly influenced by the donor (p less than 0.0001) and each of the two coal extracts (p less than 0.0001). From studies of workers occupationally exposed to coal dust, it is known that inhaled coal dust is cleared from the lungs by mucociliary action and introduced into the stomach by swallowing. Coal dust, or coal dust plus snuff, may be responsible for the increased frequency of gastric cancer observed in coal miners. The findings presented here suggest that coal dust, with or without tobacco snuff, may play a role in the elevated incidence of gastric cancer in coal miners. Because water extracts of some ranks of coal induced SCEs, there exists the possibility of adverse environmental effects due to coal leachates. PMID- 4043022 TI - Interaction of nitrilotriacetic acid with heavy metals in the induction of sister chromatid exchanges in cultured mammalian cells. AB - The ability of nitrilotriacetic acid trisodium salt (NTA) to induce sister chromatid exchanges (SCE) and to influence the induction of SCE by heavy metal compounds was evaluated with mammalian cell cultures. In accordance with the generally negative results obtained by other investigators on the mutagenic effects of NTA, no increase of SCE frequency was observed in Chinese hamster cells (CHO line) or in primary cultures of mouse (BALB/c and BALB/Mo strains) lymphocytes, after treatment with NTA at subtoxic concentrations (2 X 10(-3) M and 10(-3) M, respectively). The induction of SCE by salts of heavy metals (Cd, Hg, Ni, Pb) was evaluated with CHO cells. Soluble (CdCl2, HgCl2, NiCl2, Pb [CH3COO]2) and insoluble (CdCO3, HgCl, NiCO3, PbSO4) compounds were tested, and, with the exception of Pb(CH3COO)2, all were found to increase the frequency of SCE. NTA apparently did not affect the ability of the soluble metal compounds to induce SCE, but it significantly increased the frequency of SCE induced by treatment with all the insoluble salts. PMID- 4043023 TI - Aneuploidy and health risk assessment: current status and future directions. AB - The U.S. Environmental Protection Agency (EPA) recently sponsored a workshop to discuss the contribution of aneuploidy to human disease and disability, the development of tests for detecting chemicals that induce aneuploidy and the relevance of these tests to human risk, and the current understanding of mechanisms by which aneuploidy arises. This summary is based on the presentations given at the workshop. It is hoped that this summary will stimulate thinking in this vitally important area of risk assessment and contribute to the establishment of priorities for basic research, development of new test methods, and validation of existing test approaches. Such research is needed to enhance the scientific basis of risk assessment for aneuploidy-producing chemicals. PMID- 4043024 TI - Sister chromatid exchanges in adult epileptic patients on phenytoin therapy. AB - Sister chromatid exchanges (SCE) were studied in lymphocyte cultures of 12 adult male epileptic patients on long-term monotherapy with phenytoin (PHT) and of matched controls. Significantly increased frequency of SCE was observed in the epileptic patients as a group and in almost all individuals, indicating a detectable chromosome damaging effect of PHT therapy on its human users. PMID- 4043025 TI - Chemical enhancement of survival in aggregation of retrovirus-infected rat cells: an interlaboratory comparison. AB - This study provides a comparative evaluation among three independent laboratories of the responses to 16 chemicals in the retrovirus (Rauscher leukemia) infected Fischer rat embryo (RIFRE) cell-survival-in-aggregation assay. When suspended in liquid media above an agar base, control cells showed a rapid decline in cell survival, whereas cells that had previously been treated with chemical carcinogen survive in suspension longer than control cells. The endpoint, survival in aggregation, is measured by counting viable cells dissociated from aggregates in suspension for 4 days. By modifying previously reported procedures, we have improved the system so that a clear differential (positive or negative) response is achieved by cells treated with either a known carcinogen or known noncarcinogen. Using procedures designed to minimize assay variability, replicate assays were performed and the data analyzed for inter- and intralaboratory concordance. The RIFRE cell-survival-in-aggregation assay demonstrated a high degree of interlaboratory reproducibility in assessing the overall positive or negative responses of known carcinogens and noncarcinogens, and good qualitative reproducibility in assessing compounds tested under code. The assay could discriminate between known carcinogens and noncarcinogens. All chemicals were tested without the addition of a metabolic activation system. Cells exhibiting carcinogen-induced enhancement of survival in aggregation, when plated back onto a solid substrate and carried in culture, subsequently expressed transformation associated changes in their cellular morphology, growth in semisolid media, and tumorigenicity in nude mice. These results indicate that retrovirus-infected Fischer rat embryo cells detect a carcinogen-mediated early event that progresses to neoplastic phenotypes. Survival in aggregation appears to require the presence of the exogenous retrovirus, since uninfected cells did not show a differential survival response when carcinogen-treated, noncarcinogen-treated, or control cells were compared. This system provides a reproducible method of detecting carcinogenic chemicals based on their ability to induce enhanced survival in aggregation of treated cells. PMID- 4043026 TI - Boots for oily surfaces. PMID- 4043027 TI - Progress in the prevention of falls caused by slipping. PMID- 4043029 TI - Slipping, tripping, and falling. 2d Biennial Conference on Slipping, Tripping, and Falling Accidents. Surrey, England. PMID- 4043028 TI - Operational experience with a portable friction testing device in university buildings. PMID- 4043030 TI - Slipping, tripping and falling accidents at work: a national picture. PMID- 4043031 TI - Falls in the healthy elderly: predisposing causes. PMID- 4043032 TI - Slipping, tripping and falling accidents to delivery drivers. PMID- 4043033 TI - Femoral neck fractures: are some preventable? PMID- 4043034 TI - Review of stair-safety research with an emphasis on Canadian studies. PMID- 4043035 TI - Ergonomics international 1985. Reviews and indexes. PMID- 4043036 TI - The nature and measurement of stress. PMID- 4043037 TI - Fitness for work: bridging the gap in ergonomics. PMID- 4043038 TI - Effects of L-carnitine loading on the aerobic and anaerobic performance of endurance athletes. AB - L-Carnitine (L-C), a well known physiological carrier across the inner mitochondrial membrane of activated long chain fatty acids and acceptor of acyl groups from acyl-CoA, has been recently synthesised industrially. This has made it possible to study the effects of L-C loading (4 g X d(-1) by mouth over a period of 2 weeks) on the aerobic and anaerobic performance of 6 long distance competitive walkers. As a result of the treatment: 1) mean total, free and esterified serum L-C both at rest and shortly after completing a 120 min walk at about 65% of the individual maximal aerobic power (VO2max) were significantly increased; 2) VO2max increased 6%, from 54.5 +/- 3.7 (S.D.) to 57.8 +/- 4.7 m1O2 X kg(-1) X min(-1) (P less than 0.02); 3) blood lactate concentration (Lab) as a consequence of short bouts repeated exercise (series of 10, 15 and 20 jumps off both feet on a force platform) was unchanged; 4) heart rate, pulmonary ventilation, oxygen consumption, and respiratory quotient in the same conditions as for 1) were unchanged. It is concluded that, in trained athletes, as a consequence of L-C loading VO2max is slightly but significantly raised, probably as a result of an activation of substrate flow through the TCA cycle, whereas the lipid contribution to metabolism in prolonged submaximal exercise remains unchanged. PMID- 4043039 TI - Habituation of the cold pressor response in normo- and hypertensive human subjects. AB - The changes in cardiovascular response to repeated cold-pressor test were studied in young normotensive and in young hypertensive subjects. The cold stimulus consisted of immersing one foot in cold water (4 degrees C) for 60 s. Non invasive methods were used to record the cardiovascular responses: blood flow of the calf was measured using venous occlusion plethysmography, arterial blood pressure with sphygmomanometery, heart rate with electrocardiography. The vascular conductance level in the calf was higher in hypertensive subjects than in normotensives. The difference remained throughout the series of 6 daily experiments. In both hypertensive and normotensive groups of subjects some individuals responded to the cold stimulus with vasodilatation in the calf muscles, others with vasoconstriction. In the hypertensives blood flow increased more and habituation was only transient with a strong tendency for the vasodilatory response to recover, while in normotensives habituation was rapid and complete. Vasoconstrictor responses showed no signs of reduction. The blood pressure increases were larger in hypertensives and remained unaltered within the period of repeated tests (6 days). There was not significant difference between the heart rate changes in the two groups of subjects. It is concluded that the vasculature of the calf shows lower tone and is more labile during the early stage of hypertension.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4043040 TI - Responses of the lower limb to load carrying in walking man. AB - Muscle activity patterns of several lower limb muscles were examined in the left leg of normal human subjects walking at comfortable speed on a treadmill. In addition knee angular changes and the durations of the swing and stance phases of the step cycle were recorded. Data were collected during a period of normal control walking and when the subject carried a load, either in his right or left hand or on his back. Load (up to 20% of body weight) carried in either hand caused minimal changes in the kinematic parameters investigated but evoked significant prolongation of the normal ongoing electromyographic activity in the contralateral Gluteus medius and in the ipsilateral Gastrocnemius, Vastus lateralis and Semimembranosus. Load (up to 50% of body weight) carried on the back significantly shortened the swing phase and prolonged the ongoing electromyographic activity of the Vastus lateralis. These findings would seem to indicate that the activity of the leg musculature during walking is so tightly controlled that deviation from the normal kinematic pattern of the legs is largely prevented even when body posture and balance are disturbed by carrying substantial additional load. PMID- 4043041 TI - Blood lactate vs. exhaustive exercise to evaluate aerobic fitness. AB - This study compared the predictive power of a lactate-related index determined during submaximal cycle exercise to that of an exhaustive cycle ergometer test for evaluating the endurance exercise capacity of soldiers. The subjects (n = 48 males) performed a continuous exercise test to voluntary exhaustion on the cycle ergometer. Power output (PO) increased by 50 W steps each fourth min, with determinations of heart rate (HR), RPE and blood lactate concentrations (HLa) just prior to each PO increase. The PO at a 4 mmol L(-1) HLa concentration (WOBLA) was interpolated; based on the time to exhaustion the maximal PO that could be maintained for 6 min (Wmax6) was calculated from previously documented formulae. Subjects were timed during a 3000 m cross-country run. Both the cycle test and the run were performed again 3 months later, as was an additional 3000 m run with full military equipment weighing about 21 kg. All 3000 m times were significantly correlated (p less than 0.05) with both Wmax6 and WOBLA; similar predictive power was demonstrated for both Wmax6 and WOBLA, suggesting that accuracy in evaluation would not be sacrificed by substituting the submaximal for the exhaustive exercise test. HR and RPE-related indices showed markedly lower predictive power. The results extend the previously documented relationship between HLa during treadmill ergometry and running performance to include the use of cycle ergometry for the evaluation of running performance. The results also proved applicable to running performance while load carrying. PMID- 4043042 TI - Sympathetic control of the forearm blood flow in man during brief isometric contractions. AB - Experiments were performed to assess the possible neurally mediated constriction in active skeletal muscle during isometric hand-grip contractions. Forearm blood flow was measured by venous occlusion plethysmography on 5 volunteers who exerted a series of repeated contractions of 4 s duration every 12 s at 60% of their maximum strength of fatigue. The blood flows increased initially, but then remained constant at 20-24 ml X min(-1) X 100 ml(-1) throughout the exercise even though mean arterial blood pressure reached 21-23 kPa (160-170 mm Hg). When the same exercise was performed after arterial infusion of phentolamine, forearm blood flow increased steadily to near maximal levels of 38.7 +/- 1.4 ml X min(-1) X 100 ml(-1). Venous catecholamines, principally norepinephrine, increased throughout exercise, reaching peak values of 983 +/- 258 pg X ml(-1) at fatigue. Of the vasoactive substances measured, the concentration of K+ and osmolarity in venous plasma also increased initially and reached a steady-state during the exercise but ATP increased steadily throughout the exercise. These data indicate a continually increasing alpha-adrenergic constriction to the vascular beds in active muscles in the human forearm during isometric exercise, that is only partially counteracted by vasoactive metabolites. PMID- 4043043 TI - Human erythrocyte superoxide dismutase activity during deep diving. AB - As the practical use of high pressure oxygen (HPO) in clinical medicine and the offshore industries accelerates, knowledge of its toxic nature becomes essential. In this study, divers' erythrocyte superoxide dismutase (SOD) activity was monitored during high pressure exposure and shown to decrease on average by 20% at depths greater than 150 m. Assay of total red cell SOD protein and activity established that the recorded SOD activity decrement was by loss of immuno measurable enzyme. No evidence of intra-cellular Heinz bodies was observed. An increase of intra-membrane lipid peroxidation products, within physiological limits, was found, particularly in the denser cell fractions. Using previously in vivo pressure stressed cells, experiments at increasing O2 pressures educed that human red blood cells were oxygen "resistant" up to ten times the normal atmospheric pressure, 0.021 MPa (0.21 bar). Thereafter, a loss in SOD enzyme activity occurred with hemolysis during the in vitro decompression procedure. PMID- 4043044 TI - Blood flow in the emissary veins of the human head during hyperthermia. AB - The direction of the blood flowing in the emissary veins (vena emissaria mastoidea and v. e. partietalis) was recorded in human subjects during moderate hyperthermia and hypothermia. During hyperthermia the blood flowed rapidly from skin to brain. During hypothermia either no flow could be detected or the blood flowed slowly from brain to skin. On two fresh cadavers the calvaria was removed with the scalp adhering. Gentle massaging of the scalp produced abundant drops of blood on the inner surface of the bone each time the scalp was massaged, thus showing that cutaneous blood can flow inward through the bone. These results support the hypothesis of selective brain cooling in hyperthermic humans by offering a possible mechanism. PMID- 4043045 TI - Changes in isometric function following rhythmic exercise. AB - Seven male subjects exercised for 1, 3, 10 and 20 min on a cycle ergometer at 20, 60 and 80% VO2max, and then held to fatigue a sustained contraction of the quadriceps at 40% maximal voluntary contraction in order to determine what influence various levels of dynamic exercise would have on isometric function of the same group of muscles. Muscle temperature was measured before and within 15 s of the completion of the cycling to determine whether changes in muscle temperature might influence the subsequent isometric performance. Isometric endurance was shorter as the severity of the cycling increased beyond 20% VO2max, and as the duration of cycling increased up to 10 min. There were discrete linear relationships between muscle temperature and isometric endurance associated with cycling at 60% and 80% VO2max. There was a direct inverse relationship between quadriceps strength after cycling and muscle temperature, yet a significant reduction in strength occurred only after cycling at 80% VO2max. These results suggest that the encroachment on endurance and strength are controlled by different mechanisms. The heart rates during the isometric contractions were dependent on the preceding rhythmic exercise and decreased after exercise at 60 or 80% VO2max. In contrast, the blood pressure always increased during the isometric contractions, reaching similar values at the point of fatigue, regardless of the severity of the previous rhythmic exercise. These data provide additional evidence that separate mechanisms control changes in heart rate and blood pressure. PMID- 4043046 TI - Morphological changes in continuously stretched skeletal muscles in sheep. AB - The effects of continuous elongation of skeletal muscles were studied on six sheep who underwent a lengthening osteotomy of the right tibia. Open muscle biopsies were taken from the biceps femoris muscle preoperatively (Group A), after 5 weeks of bone distraction (Group B) and after another 5 weeks without further distraction (Group C). The size and distribution of type 1 (slow-twitch) and type 2 (fast-twitch) muscle fibres were determined from sections stained for myofibrillar ATPase activity. All sections were also evaluated by light microscopy, especially with regard to myopathic changes. The type 2 fibres showed a significant decrease in size from group A to B and from group B to C. The reduction in fibre size from group A to C was 44.2%. The type 1 fibres, on the other hand, showed no significant differences in mean fibre size between the groups. However, there were considerable individual variations in type 1 fibre size between the groups. The distribution of both fibre types was similar in groups A and B (appr. 17% type 1 fibres) whereas the relative number of type 1 fibres was reduced to 12.4% in group C (P less than 0.01). Myopathic changes, i.e. muscle fibre necroses, were not seen in any of the groups. It is concluded that the type 2 fibre atrophy is mainly caused by muscular inactivity during the postoperative period, but an additional effect of continuous stretching of the muscle cannot be excluded.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4043047 TI - Fitness changes in an Australian Antarctic expedition. AB - Serial fitness testing using a cycle ergometer and a submaximal work-load technique was performed monthly on 22 expeditioners at Davis Station, Antarctica, during the period February 1982 to January 1983. The results showed a linear increase in fitness in the group over the 12 month study period, including the winter period when outdoor activities were limited. The regression equation for fitness (measured as maximum oxygen uptake) was VO2max (ml . min-1 . kg-1) = 43.96 + 0.631 (time) where time is the month number from 1 through to 12. The correlation coefficient of the regression line representing fitness plotted against time in months was 0.918 (p less than 0.001). It is evident that indoor station activities and limited outdoor activities were more than adequate to maintain physical fitness in the winter period. Pre-departure fitness assessment for expeditioners is suggested. As fitness was lowest on arrival in Antarctica yet station workloads heaviest at this time, physical training prior to arrival in Antarctica is recommended for future expeditions. PMID- 4043048 TI - A comparison of the effects of mixed static and dynamic work with mainly dynamic work in hot conditions. AB - Current physiological criteria for limiting work in hot conditions are frequently based on responses to mainly dynamic work (eg treadmill walking). Their applicability to industrial situations containing mixed static and dynamic work is questioned, since the physiological responses to static work are different from those of dynamic work. Each of eight subjects attempted a one hour uphill treadmill walk (mainly dynamic work), and an uphill treadmill walk whilst intermittently carrying a 20 kg weight in the arms (mixed static and dynamic work). The external work rates in the two conditions were equal, effected by lowering the treadmill gradient in the loaded condition. Experiments were conducted in a hot climate (33 degrees C dry bulb, 25 degrees C wet bulb). Oxygen consumption, minute ventilation, sweat rate and rated perceived exertion were all significantly higher (p less than 0.001) for the mixed static and dynamic work than for the dynamic work. This was also the case for heart rate and forearm skin temperature (p less than 0.01), and for auditory canal temperature (p less than 0.05). There was no significant difference between the two types of work for mean skin temperature, calf skin temperature and chest skin temperature. These results show that for the same external work, physiological strain and perceived exertion are greater for mixed static and dynamic work (carrying a load in the arms) than for mainly dynamic work (walking on a treadmill). They suggest that it is not appropriate to make direct comparisons of laboratory studies based on dynamic work, with practical situations containing mixed static and dynamic work in the heat. PMID- 4043049 TI - Creatine kinase MB and citrate synthase in type I and type II muscle fibres in trained and untrained men. AB - Total creatine kinase (CK), creatine kinase MB (CK-MB) and citrate synthase (CS) were determined in isolated and pooled type I and type II skeletal muscle fibres. Determinations were made on biopsies from 3 sedentary men, 3 junior cyclists and 2 elite cyclists. CS and CK-MB activities were higher in the trained groups in both fibre types. The total CK activity was not related to training status, although it was lower in type I fibres than in type II fibres (p less than 0.05). The reverse relation was observed for CS and CK-MB activities (p less than 0.01). The ratio of type I/type II for CS was not related to training status, while the corresponding ratio for CK-MB increased with a greater degree of endurance training. For a given increase in CS activity, the increase in CK-MB activity was greater in type I fibres than in type II fibres (p less than 0.01). Thus, with endurance training there seems to be a specific adaptation for CK-MB, particularly in type I fibres. PMID- 4043050 TI - A dynamometer for the measurement of force, velocity, work and power during an explosive leg extension. AB - A dynamometer for measurement under static and dynamic conditions is presented. At different load levels, force, velocity, work and power can be measured in explosive leg extensions. Measurements on 53 subjects at different load levels (0 125.5 kg) were carried out. Peak power ranged from 2611 to 1746 W, force from 1351 to 1899 N, velocity from 1.61 to 0.89 m X s-1 and work from 329 to 605 J. Between trial correlation coefficients ranged from 0.72 to 0.95. The dynamometer is compared with others, and it is concluded that data obtained by this dynamometer have a greater practical validity. PMID- 4043051 TI - Effects of previous muscle contractions on cyclic movement dynamics. AB - In addition to muscle elastic energy, enhancement of movement performance in a stretch-shortening cycle could also be due to an increase in initial muscle force during the stretching phase. This hypothesis was tested by examining 9 male physical education students during maximum voluntary knee extensions performed with and without previous knee flexion. In both conditions movements were performed with various external loads. In addition, the force-velocity curve (FVC) parameters of the knee extensor muscles were also determined. As simple model of a muscle impulse was constructed in order to select independent biomechanical variables relevant to movement dynamics. The experimental results demonstrated that previous knee flexion enhanced the maximum angular velocity of knee extension. This effect decreased with increasing movement duration (i.e. increased external load), as well as giving positive correlation coefficients between the magnitude of this effect and the rate of development of knee extensor tension. These results are discussed in relation to a model of the dynamics. It is shown that previous muscle contractions performed during braking in the negative movement phase might play an important role in enhancing performance in cyclic movements. This role would be especially important in transient contractions of primarily slow twitch fiber muscles. PMID- 4043052 TI - All out anaerobic capacity tests on cycle ergometers. A comparative study on men and women. AB - We have studied the effects of the braking force on the results of an anaerobic capacity test derived from the Wingate test (an all out 45 s exercise on a Monark 864 cycle ergometer against a given force at the fastest velocity from the beginning to the end of the test). Seven men and seven women participated in the study and performed a total of 63 all-out tests against different braking forces. The same subjects performed a force-velocity test on the same cycle ergometer. Since the relationship between force and velocity is approximately linear for peak velocities between 100 and 200 rev X min-1 (Peres et al. 1981a, b; Nadeau et al. 1983; Vandewalle et al. 1983) we characterized each subject by three parameters: P0 (the intercept of the force-velocity regression line with the force axis), V0 (the intercept of the regression line with the velocity axis) and Wmax (maximal power). The relationship between force and mean power was parabolic for the all-out anaerobic capacity test. In the present study the optimal force (the force giving the maximal value of mean power during an all out test) was higher for the men (approximately 1 N X kg BW-1) than the force proposed by others (0.853 N X kg BW-1 for Dotan and Bar-Or 1983). However, because of the parabolic relationship between force and mean power, the mean power which corresponds to the optimal force was approximately the same in both studies.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4043053 TI - Testing phagocytic cell function. PMID- 4043054 TI - Endotoxin testing revisited. PMID- 4043055 TI - Clinical significance of Streptococcus milleri. AB - The clinical features of infection in patients from whom Streptococcus milleri was isolated were analysed in an attempt to determine the clinical significance of this organism. During a four-year period Streptococcus milleri was isolated from 232 hospitalized patients. In 44 patients Streptococcus milleri was isolated in pure culture, in 45 patients together with obligate anaerobes, and in 143 patients together with aerobes with or without anaerobes. The 82 patients in whom isolation of Streptococcus milleri was considered significant had the following infections: bacteremia (8 patients), brain abscess (2), pleural empyema (9), lung abscess (1), maxillary sinusitis (7), intra-abdominal abscess (53), infection of pacemaker (1) and infection of vascular graft (1). The 150 patients in whom isolation of Streptococcus milleri was considered of questionable significance had the following: upper respiratory tract infection (12 patients), lower respiratory tract infection (6), acute cholecystitis (8), soft tissue abscess, cellulitis and surgical wound infections (83), bone and joint infections (14), genital infection (25) and miscellaneous infections (2). The overall incidence of infection with Streptococcus milleri was five cases per 1000 admissions. The study showed that Streptococcus milleri is of clinical significance not only in suppurative infections, as previously reported, but also in acute maxillary sinusitis and infection of implant material. PMID- 4043056 TI - Fatty acid composition of Streptococcus milleri. AB - The cellular fatty acids of 31 strains belonging to the Streptococcus milleri group were analysed by capillary gas-liquid chromatography. Results were compared with findings from biochemical differentiation of the strains into Streptococcus constellatus (two strains), Streptococcus anginosus (16 strains) and Streptococcus intermedius (13 strains). Eight strains of various other streptococci were included as internal references, including three strains of streptococcus morbillorum, three strains of beta-hemolytic streptococci, and two strains of enterococci. The Streptococcus milleri strains formed a very homogeneous group according to fatty acid composition and were easily differentiated from other groups. However, within the group, it was not possible to differentiate Streptococcus constellatus, Streptococcus anginosus and Streptococcus intermedius by fatty acid composition alone. PMID- 4043057 TI - Activity of BAY n 7133 and BAY 1 9139 in vitro and in experimental murine coccidioidomycosis. AB - The activity of two new antifungal azoles, BAY n 7133 and BAY 1 9139, against Coccidioides immitis was compared with that of ketoconazole in vitro and in experimental murine coccidioidomycosis. Daily intravenous injections were given for 30 days. All mice were autopsied and suspensions of lung, liver and spleen cultured. BAY n 7133 was as active as ketoconazole while Bay 1 9139 was les active. All three drugs were coccidioidostatic only both in vitro and in vivo. PMID- 4043058 TI - Detection of anaerobic bacteria in blood cultures by lysis filtration. AB - An anaerobic adaptation of the lysis-filtration system for detection of anaerobic microorganisms in blood is described. The method was compared with a conventional broth bottle system in detection of anaerobic bacteremia after oral surgery. Of 43 blood samples obtained during and after surgery, 31 were positive with the lysis-filtration system and 17 were positive with the broth bottle system. Sixteen aerobic and 62 anaerobic strains were isolated with the lysis-filtration system versus 9 aerobic and 22 anaerobic strains with the broth bottles. The lysis-filtration technique was thus superior to the conventional broth bottle method in detecting anerobic bacteria. PMID- 4043059 TI - Hepatitis B vaccination campaign in a low endemicity area. AB - Between January 1982 and December 1983 14,666 high-risk individuals in the Canton of Zurich, which has one million inhabitants, received 36,234 hepatitis B vaccine injections. The annual number of acute hepatitis B cases dropped from an estimated 220 to 280 in 1981 to 177 in 1982 and 133 in 1983. This drop of 40-50% resulted mainly from reduced numbers of cases among health care workers, drug addicts and homosexuals. Vaccination was a factor responsible for the reduced incidence of hepatitis B among health care workers and drug addicts, high-risk categories substantial proportions of which had been vaccinated. There was no evidence of a secondary protective effect of vaccination extending to other high risk groups. PMID- 4043060 TI - Outbreak of respiratory syncytial virus in France. AB - A report is given of an outbreak of respiratory syncytial virus infection in a neonatal unit in France. Twenty-three of 32 infants were infected (72%) despite infection control procedures. Prophylactic administration of non-specific gamma globulins was associated with a significant decrease in infection rate (p less than 0.05). The administration of transfer factor to infected infants was also associated with a significantly lower rate of severe respiratory diseases (p less than 0.05). PMID- 4043061 TI - Meningitis and brain abscess due to Haemophilus paraphrophilus. AB - A case of meningitis and brain abscess due to Haemophilus paraphrophilus in a patient with congenital heart disease is reported. The abscess communicated with the cerebral ventricular system. Although the infecting strain was found to be highly sensitive to ampicillin, the patient died despite appropriate antimicrobial therapy. Characteristics distinguishing Haemophilus paraphrophilus and related species are discussed. PMID- 4043062 TI - Stomatococcus mucilaginosus endocarditis. AB - A case of non-nosocomial, spontaneously occurring endocarditis caused by growth of Stomatococcus mucilaginosus on a prolapsed mitral valve is reported. Despite the organism's high susceptibility in vitro the patient responded slowly to antibiotic treatment. Colony adherence to agar surface and absent or weak catalase reaction differentiated this gram-positive coccus from coagulase negative staphylococci and micrococci. PMID- 4043063 TI - Rarity of Legionella species in routine sputum specimens. PMID- 4043064 TI - Gastric juice microflora in patients with gastric ulcer and gastric cancer. PMID- 4043065 TI - Neonatal conjunctivitis caused by Pasteurella ureae. PMID- 4043066 TI - Isolation of Actinobacillus actinomycetemcomitans from a skin lesion. PMID- 4043067 TI - First isolation of Neisseria polysacchareae species nova in the Federal Republic of Germany. PMID- 4043068 TI - Loss of viability of Bacteroides fragilis and Bacteroides vulgatus in different media. PMID- 4043069 TI - Analysis of gram-positive anaerobic cocci in oral, fecal and vaginal flora. PMID- 4043070 TI - Isolation of Campylobacter species by filtration. PMID- 4043071 TI - Identification of Clostridium difficile by detection of p-cresol in a cooked meat medium. PMID- 4043072 TI - Lyme arthritis: does endotoxin play a role? PMID- 4043073 TI - Internalization of the vasoactive intestinal peptide (VIP) in a human adenocarcinoma cell line (HT29). AB - The time course of internalization of radioiodinated vasoactive intestinal peptide (VIP) in HT29 cells was obtained using the technique of acetic acid removal of cell-surface-bound peptide. Even after 10 min incubation at 37 degrees C, 125I-VIP, initially bound on the HT29 cell surface, was compartmentalized within the cells. During the same time, degraded radioactive material was released by cells in the incubation medium. Localization of internalized 125I-VIP was investigated using two different subcellular fractionation techniques. 10 min after the onset of internalization, 125I-VIP labelling was found in intermediate structures and 10 min later the bulk of the radioactivity was detected in a low density fraction containing very large lysosomes with a multivesicular aspect. The lysosomotropic agent NH4Cl appeared to inhibit 125I-VIP internalization, degradation and appearance of radiolabelled peptide in the large lysosomes in a time-dependent manner. Moreover, the effect of NH4Cl resulted in an accumulation of radioactive material in fractions containing microsomal structures. On the other hand, bacitracin, together with methylamine, highly enhanced 125I-VIP labelling in a membrane fraction, suggesting that these agents possibly act on a cell surface component of HT29 cells. These results support the conclusion that in HT29 cells, prelysosomal structures and large secondary lysosomes are probably part of the intracellular pathway of internalized VIP. PMID- 4043074 TI - Stimulation by 3-hydroxybutyrate of pyruvate carboxylation in mitochondria from rat liver. AB - Isolated rat liver mitochondria incubated in the presence of 3-hydroxybutyrate display a markedly increased rate of pyruvate carboxylation as measured by malate and citrate production from pyruvate. The stimulation was demonstrable both with exogenously added pyruvate, even at saturating concentration, and with pyruvate intramitochondrially generated from alanine. The concentration of DL-3 hydroxybutyrate required for half-maximal stimulation amounted to about 1.5 mM. The intramitochondrial ATP/ADP ratio as well as the matrix acetyl-CoA level was found to remain unchanged by 3-hydroxybutyrate exposure, which, however, lowered the absolute intramitochondrial contents of the respective adenine nucleotides. The effects of 3-hydroxybutyrate were diminished by the concomitant addition of acetoacetate. Moreover, a direct relationship between mitochondrial reduction by proline and the rate of pyruvate carboxylation was observed. The results seem to indicate that the mitochondrial oxidation--reduction state might be involved in the expression of the 3-hydroxybutyrate effect. As to the physiological relevance of the findings, 3-hydroxybutyrate could be shown to activate pyruvate carboxylation in isolated hepatocytes. PMID- 4043075 TI - The structure of sub-nucleosomal particles. The octameric (H3/H4)4--125-base-pair DNA complex. AB - Chicken erythrocyte chromatin was depleted of histones H1, H5, H2A and H2B. The resulting (H3/H4)-containing chromatin was digested with micrococcal nuclease to yield monomer, dimer, trimer etc. units, irregularly spaced on the DNA, with even number multimers being more prominent. Sucrose density gradient centrifugation separated monomers and dimers (7.7 S and 10.5 S). Sodium dodecyl sulphate gel electrophoresis and cross-linking indicated: the monomer contains 50-base-pair (bp), 60-bp and 70-bp DNA and the dimer 125-bp DNA; the monomer contains a tetramer and the dimer an octamer of H3 and H4. Partial association of monomer units to dimers inhibits structural studies of monomers. The internal structure of the dimer, i.e. and (H3/H4)4-125-bp-DNA particle, was studied using circular dichroism, thermal denaturation and nuclease digestion. Both micrococcal nuclease and DNase I digestion indicate that, unlike core particles, accessible sites occur in the centre of the particle and it is concluded that the (H3/H4)4-125-bp DNA particle is not a 'pseudo-core particle' in which the 'extra' H3 and H4 replace H2A and H2B. It is proposed that the octamer particle is formed by the sliding together of two 'monomer' units, each containing the (H3/H4)2 tetramer and 70 bp of DNA. Excision of this dimer unit with micrococcal nuclease results in the loss of 10 readily digestible base pairs at each end, leaving 125 bp. PMID- 4043076 TI - Two-dimensional nuclear Overhauser enhancement investigation of the solution structure and dynamics of the DNA octamer [d(GGTATACC)]2. AB - The resonances of nearly all 70 of the non-exchangeable protons of the duplex [d(GGTATACC)]2 in aqueous solution are assigned by proton two-dimensional nuclear Overhauser enhancement (2D NOE) spectra obtained in pure absorption phase at 500 MHz. Experimental and theoretical 2D NOE spectra are compared at each mixing time (100, 175, 250 and 400 ms) using two B-DNA structures: a standard B-form and an energy-minimized form. The GG and CC ends of the octamer duplex are well represented by the regular B-DNA structure. But large discrepancies from these models are observed for the 'TATA' box. All 2D NOE data are consistent with nanosecond correlation times, as indicated by non-selective proton spin-lattice relaxation times, but small variations in the correlation time are observed, suggesting that there are some local differences in mobility within the octamer duplex structure in solution. PMID- 4043077 TI - Reductive mobilisation of ferritin iron. AB - The reductive mobilisation of iron from ferritin, the principal protein of iron storage, was studied. The kinetic characteristics of iron release by dithionite, thioglycollate, and dihydroriboflavin 5'-phosphate (FMNH2) were found to differ widely. The dependence on pH is most pronounced for the dithionite reduction which proceeds 100 times faster at pH 4 than at pH 7. The experimental data can be consistently explained in terms of specific interactions of products or educts with interfacial iron(III) hydroxide of the ferritin core. Surface complexes with the product sulfite are postulated in the dithionite reaction, and with the educt in the thioglycollate reaction. Iron(II) complexes with the radical anion FMN-. are suggested to be involved in the iron release by FMNH2. The mobilisation of iron by a series of thiols of different size and coordinative properties confirmed the importance of surface complex formation. No evidence was found for predominant effects of hindered shell penetration. PMID- 4043078 TI - Synthesis of ribulose biphosphate carboxylase in greening pea leaves. Coordination of mRNA level of two subunits. AB - Ribulose biphosphate carboxylase/oxygenase, with its large subunit encoded in the chloroplast and the small subunit in the nucleus, is induced by light. Accumulation of the enzyme, its two mRNA levels, and the synthesis rate of enzyme protein in pea leaves were followed during induction to understand the role of mRNA levels during greening subunit synthesis. The relative mRNA levels for the large and the small subunits increased coordinately up to 3-4 days, which almost corresponded to an inflection point of the accumulation profile of RuBisCO, and then the two mRNA levels gradually decreased. To obtain information of subunit synthesis, the extent of labelling of the two subunits were determined for both assembled and unassembled subunits using specific IgG. Unassembled subunits were found for both polypeptides, with a slight excess of the small one. The observed synthesis rates of the small and the large subunits were roughly coordinated without overproduction and almost stoichiometric amounts of the two polypeptides were found. The profiles of observed synthesis rate of the two subunits and the holoenzyme were similar to those of their mRNA levels. These results suggest that the synthesis of ribulose biphosphate carboxylase/oxygenase protein and its accumulation are dependent on the coordinated change of the two mRNA levels in greening pea leaves. PMID- 4043079 TI - Hydrolysis of very-low-density lipoproteins labeled with a fluorescent triacylglycerol: 1,3-dioleoyl-2-(4-pyrenylbutanoyl)glycerol. AB - The fluorescent triacylglycerol (DPBG) 1,3-dioleoyl-2-(4-pyrenylbutanoyl)glycerol was incorporated into plasma very-low-density lipoproteins (VLDL) to form DPBG VLDL. In the presence of albumin, the addition of milk lipoprotein lipase to DPBG VLDL hydrolyses DPBG together with the VLDL triacylglycerol and pyrenyl fatty acids are transferred to albumin. As a consequence the monomer fluorescence increases while that of the excimer decreases [Mantulin, W. W., Massey, J. B., Gotto, A. M., Jr & Pownall, H. J. (1981) J. Biol. Chem. 256, 10815-10819]. The relationship of the intensity of the excimer at 475 nm to that of the monomer at 396 nm was measured before and after lipolysis of VLDL by milk lipoprotein lipase. These fluorescent changes parallel the release of free fatty acids from VLDL and their uptake by albumin. The rate of increase of monomer to excimer fluorescence was dependent upon the enzyme, substrate and albumin concentration. The lipolysis reaction, as monitored by fluorescence changes, followed Michaelis Menten kinetics with a Km of 1.7 M for milk lipoprotein lipase. The use of the fluorescent triacylglycerol probe increases the sensitivity of the technique by a factor 50-80 compared to a technique previously reported using a fluorescent phospholipid. The present method is applicable to 2-10 micrograms triacylglycerol corresponding to about 50-100 microliters of newborn plasma or 30-50 microliters normal adult plasma. The use of an Airfuge ultracentrifuge for VLDL isolation, in conjunction with that of DPBG as a fluorescent probe enables a rapid study of VLDL lipolysis on minimal sample amounts. It can therefore be easily applied to normal and dyslipoproteinemic samples and to the newborns. PMID- 4043080 TI - Isolation, primary structure and synthesis of heat-stable enterotoxin produced by Yersinia enterocolitica. AB - Five heat-stable enterotoxins were isolated from the culture supernatant of Yersinia enterocolitica and purified to homogeneity by DEAE-Sephacel and high performance liquid chromatographies. They caused acute fluid accumulation in the intestine of suckling mice. The amino acid sequence of one of the enterotoxins was determined to be Ser-Ser-Asp-Trp-Asp-Cys-Cys-Asp-Val-Cys-Cys-Asn-Pro-Ala-Cys Ala-Gly-Cys, by Edman degradation of its pyridylethylated derivative and a combination of fast atom bombardment mass spectrometry and carboxypeptidase B digestion. This structure was unambiguously confirmed by chemical synthesis. The other enterotoxins had longer or shorter amino acid sequences at their N termini, but the same sequence at their C termini. The six half-cystine residues formed intramolecular disulfide linkages, as shown by measurement of the molecular masses of the enterotoxins by fast atom bombardment mass spectrometry. The sequence of 13 amino acid residues at the C terminus showed similarity to those of heat-stable enterotoxins isolated from enterotoxigenic Escherichia coli [Aimoto, S. et al. (1982) Eur. J. Biochem. 129, 257-263; Takao, T. et al. (1983) FEBS Lett. 152, 1-5] suggesting that these similar sequences are related to the common biological and immunological properties of enterotoxins produced by Y. enterocolitica and enterotoxigenic E. coli. PMID- 4043081 TI - Human alpha-L-iduronidase. 1. Purification, monoclonal antibody production, native and subunit molecular mass. AB - Human alpha-L-iduronidase from liver was purified about 20 000-fold with a new rapid three-step, five-column procedure which consisted of a Concanavalin-A Sepharose/Blue-A-Agarose coupled step, a CM-Sepharose/Bio-Gel HT coupled step followed by a cupric-ion-chelating Sepharose 6B step. The behaviour of alpha-L iduronidase on gel permeation chromatography was dependent upon both pH and ionic strength of the eluting buffer. The formation of species with enzyme activity which behaved as large-molecular-mass aggregates was favoured under conditions of low ionic strength and neutral pH. The amount of high-Mr species diminished as the pH decreased or the ionic strength increased to favour a single active species of Mr 65 000. A specific monoclonal antibody was generated against liver alpha-L-iduronidase. The antibody specifically immunoprecipitated enzyme activity from both crude and purified sources. The subunit Mr of liver alpha-L-iduronidase was estimated to be 65 000 using SDS-PAGE. Monoclonal antibody immunoprecipitation of radiolabelled enzyme was used to provide definitive confirmation of this subunit size. PMID- 4043082 TI - Amino acid sequence of the N-terminal aggregation and cross-linking region (7S domain) of the alpha 1 (IV) chain of human basement membrane collagen. AB - The amino acid sequence of the 216-residue-long N-terminal aggregation and cross linking 7S domain of the alpha 1 (IV) chain of human placental basement membrane collagen is presented. The N terminus of the alpha 1 (IV) chain starts with a non triple-helical region, which is at least 15 residues long and contains four cysteine and two lysine residues as putative cross-linking sites. This segment is followed by a 120-residue-long triple helical region, which contains the unusual occurrence of a cysteine residue in the Xaa position of a Gly-Xaa-Yaa triplet. Since individual molecules in the 7S domain are associated in an antiparallel manner, this cysteine probably aligns with one of the four cysteines in the amino terminal end of an adjacent molecule, forming an intermolecular disulfide bridge. The length of the overlap of two adjacent molecules is estimated to be about 110 residues. The triple helix adjacent to the overlap zone is interrupted by a 10 residue-long non-helical area, which is probably responsible for the flexible region of the molecules in the neighbourhood of the overlap zone observed in the electron microscope. The mode of aggregation of the 7S domain, the formation of intermolecular cross-links as well as the relatively high stability of this region against proteolytic attack are discussed in the light of the elucidated amino acid sequence. PMID- 4043083 TI - Human alpha-L-iduronidase. 2. Catalytic properties. AB - The kinetic parameters of human liver alpha-L-iduronidase were determined with three disaccharide substrates: alpha-L-iduronosyl(1----4)2,5-anhydro-D-[1 3H]mannitol 6-sulphate, alpha-L-iduronosyl(1----4)2,5-anhydro-D-[1-3H]mannitol and alpha-L-iduronosyl(1----3)2,5-anhydro-D-[1-3H]talitol 4-sulphate, derived from the natural substrates heparin and dermatan sulphate and one synthetic, fluorogenic substrate, 4-methylumbelliferyl alpha-L-iduronide. The enzyme activity with all four substrates was optimal at about pH 4.5. The Km values derived using the disaccharide substrates were elevated up to 10-fold with up to a 6.5-fold increase in ionic strength whereas that for the synthetic substrate was only increased by 1.7-fold. The V values for all substrates were unaffected. The inhibitory effect of NaCl, Na2SO4, NaH2PO4 or CuCl2 on enzyme activity was more pronounced with the disaccharide substrates than with the synthetic substrate. The moiety which is most important in binding is the idopyranosyl residue. While the aglycone residue adds to the net affinity for the enzyme, it is the substituent groups of both residues which appear to control catalysis. Specifically the carboxyl moiety of the alpha-L-iduronic acid residue is essential for catalysis while the presence of sulphate on the C4 or C6 position of the aglycone residue has a major influence on catalysis rather than binding. alpha-L-Idosyl(1----4)2,5-anhydro-D-[1-3H]mannitol 6-sulphate did not undergo catalysis and was a potent inhibitor of enzyme activity, whereas beta glucuronosyl(1----4)2,5-anhydro-D-[1-3H]mannitol 6-sulphate, alpha-L-iduronosyl-2 sulphate(1----4)2,5-anhydro-D-[1-3H]-mannitol 6-sulphate and 4-methylumbelliferyl alpha-L-idoside did not undergo catalysis and were not inhibitory. A model of the catalytic requirements of alpha-L-iduronidase is proposed. PMID- 4043084 TI - Selective induction of coumarin 7-hydroxylase by pyrazole in D2 mice. AB - Pyrazole, was given to DBA/2N (D2), C57BL/6N (B6) and AKR/N mice to study its effects on hepatic drug metabolism. A decrease in the total amount of microsomal cytochrome P-450 as well as in the activities of ethylmorphine demethylase and benzo[a]pyrene hydroxylase was found. On the other hand ethoxycoumarin de ethylase was increased 1.5-2.5-fold (depending on the strain of mouse) and coumarin 7-hydroxylase as much as sevenfold (but only in D2 mice) after pyrazole treatment. This increase was much higher than that caused by phenobarbital, the only well known inducer of coumarin 7-hydroxylase. By reconstituting the mono oxygenase complex after purification of cytochrome P-450 we found a 40-fold increase in coumarin 7-hydroxylase and eightfold increase in ethoxycoumarin de ethylase after pyrazole treatment. This was found only in D2 mice. An antibody previously developed against a cytochrome P-450 fraction from the the D2 strain with a high coumarin 7-hydroxylase activity inhibited the microsomal coumarin 7 hydroxylase almost 100% after pyrazole pretreatment of the animals. In the case of control or phenobarbital-treated mice the inhibition was somewhat weaker. With the reconstituted mono-oxygenase complex the inhibition of coumarin 7-hydroxylase was almost 100% both for control and pyrazole-treated D2 mice. The data indicate that pyrazole causes an induction of the microsomal monooxygenase complex different from that caused by phenobarbital or 3-methylcholanthrene and selective for coumarin 7-hydroxylation or 7-ethoxycoumarin de-ethylation. This induction was strong in D2, weak in B6 and absent in AKR/N mice. PMID- 4043085 TI - High-mannose structure of apolipoprotein-B from low-density lipoproteins of human plasma. AB - Human plasma low-density lipoproteins were purified by flotation followed by gel filtration. The protein moiety of the lipoproteins, apolipoprotein-B, which was detected by polyacrylamide gel electrophoresis as the only protein component, contained 4.4% (by weight) carbohydrate. Glycopeptides liberated from apolipoprotein-B by pronase were fractionated by affinity chromatography on concanavalin-A--Sepharose. The results indicated that high-mannose glycopeptides interacting strongly with the lectin comprise about 37% of the total monosaccharides of apolipoprotein-B. Thus, as compared to the total serum glycoproteins having about 5% of their monosaccharides in high-mannose glycopeptides, low-density lipoproteins are relatively enriched in these structures amounting up to about 10% of the total high-mannose oligosaccharides in serum. The rest of the carbohydrates in low-density lipoproteins are suggested to be mainly biantennary acidic oligosaccharides interacting weakly with concanavalin A. The oligomannosidic chains from native low-density lipoproteins and isolated glycopeptides were released by digestion with endo-beta-N acetylglucosaminidase H. Thin-layer chromatography of the released oligosaccharides indicated that apolipoprotein-B contains five different oligomannosidic structures varying in the number of the mannose residues from Man5GlcNAc to Man9GlcNAc. Separation of the per-O-benzoylated high-mannose oligosaccharides by high-pressure liquid chromatography revealed the same polymeric structures in a molar ratio (from Man5 to Man9) of 10:2:3:2:3. Apolipoprotein-B in low-density lipoproteins was calculated to contain five high mannose chains in total. The different high-mannose oligosaccharides liberated by endo-beta-N-acetylglucosaminidase H were isolated with high-pressure liquid chromatography after reduction with NaBH4, and subjected to methylation analysis with gas-liquid chromatography--mass spectrometry. The data of these studies and the results of exoglycosidase treatment suggest the following structure for the main high-mannose oligosaccharide: (formula: see text) The higher polymeric structures are composed of chains in which the Man5GlcNAc structure is continued by one to four Man(alpha 1-2) residues. PMID- 4043086 TI - Transport of proteins into chloroplasts. The effect of incorporation of amino acid analogues on the import and processing of chloroplast polypeptides. AB - We have synthesized abnormal precursors of imported chloroplast proteins by incorporating amino acid analogues during translation in a cell-free wheat germ system. Incorporation of analogues of either proline, arginine or leucine markedly inhibits both the import of Pisum sativum ribulosebisphosphate carboxylase small subunit precursor by isolated chloroplasts and processing to the mature size by the purified processing enzyme. One effect of the arginine analogue is to remove a positive charge(s) in the precursor essential for efficient recognition by the processing enzyme. Incorporation of a lysine analogue results in moderate inhibition of the import of small subunit precursor but complete inhibition of import of the chlorophyll a/b-binding polypeptide precursor. The effect of carboxymethylation on the import of chloroplast proteins is also analyzed. The results indicate that residues essential for transport of the imported proteins by the chloroplast vary among different protein precursors. PMID- 4043087 TI - Flavobacterium heparinum 6-O-sulphatase for N-substituted glucosamine 6-O sulphate. AB - A specific glyco-6-O-sulphatase has been purified to homogeneity from Flavobacterium heparinum. The enzyme hydrolyses the 6-O-sulphates of 2-deoxy-2 sulphamido-6-O-sulpho-D-glucose (GlcNS-6S), 2-acetamido-2-deoxy-6-O-sulpho-D glucose (GlcNAc-6S) and 2-amino-2-deoxy-6-O-sulphato-D-glucose (GlcN-6S). The activity was purified 2100-fold by successive chromatography on CM-Sepharose CL 6B, Sepharose CL-4B, hydroxyapatite and blue-Sepharose CL-6B. Sodium dodecyl sulphate/polyacrylamide gel electrophoresis showed a protein of relative molecular mass 64000. Four novel assays were developed using 35S-labelled and 14C labelled monosaccharides. The purified enzyme was free of all other known heparin degrading enzymes. In particular this was the first resolution of the 6-O sulphatase from the sulphamidase. Optimal activity was at pH 7.5. Enzyme activity was virtually unaffected by Na+ and K+ ions. Enhancements of activity of 12% and 30% were effected by Mg2+ and Ca2+ ions respectively. Inorganic phosphate and sulphate (both 0.005 mol dm-3) inhibited activity by 48% and 50% respectively. The Km value for the free amino substrate GlcN-6S was 1.35 mmol dm-3. In contrast the Km values for the GlcNAc-6S and GlcNS-6S were 54 mumol dm-3 and 16 mumol dm-3 respectively. PMID- 4043088 TI - Influence of monensin on biosynthesis, processing and secretion of proteodermatan sulfate by skin fibroblasts. AB - The influence of monensin on biosynthesis, processing and secretion of proteodermatan sulfate from human skin fibroblasts was studied with the aid of a specific immunological procedure. Double-labeling experiments with [3H]leucine and [35S]sulfate indicated that monensin caused a dose-dependent parallel decrease of sulfate incorporation into total and of secretion of 3H-labeled proteodermatan sulfate. Compared with the untreated control, a greater proportion of incorporated [35S]sulfate than of incorporated [3H]leucine became secreted. Other monensin effects were a moderate intracellular accumulation of glycosaminoglycan-free core protein, a reduced chain length and a greatly reduced epimerization of D-glucuronic to L-iduronic acid residues. In contrast to the formation of N-acetylgalactosamine 4-sulfate residues 6-sulfation was not affected. Conversion of high-mannose-type oligosaccharides to complex-type N glycans which normally occurred concomitantly with glycosaminoglycan biosynthesis was inhibited. Withdrawal of monensin made possible an additional sulfation of intracellularly accumulated proteodermatan sulfate. The newly formed sulfate esters did not cluster at the non-reducing ends of the glycosaminoglycan chains. Cells preexposed to monensin and labeled with [3H]glucosamine either in the absence or continuous presence of the drug incorporated similar amounts of 3H radioactivity into proteodermatan sulfate. The results suggest that epimerization of D-glucuronic acid residues and 4-sulfation occur predominantly in the trans cisternae of the Golgi apparatus whereas chain polymerisation and 6-sulfation take place predominantly in the cis Golgi complex. PMID- 4043089 TI - Consequences of methylation on the amino group of adenine. A proton two dimensional NMR study of d(GGATATCC) and d(GGm6ATATCC). AB - A two-dimensional 500-MHz 1H-NMR study of two oligonucleotides, d(GGATATCC) and d(GGm6ATATCC), is presented in which we have investigated the effects of adenine methylation. The two-dimensional nuclear Overhauser spectra (NOESY) show that both oligonucleotides adopt a normal right-handed B-type helix and one dimensional nuclear Overhauser enhancement (NOE) studies demonstrate that any difference in conformation must be small. However methylation drastically slows down the helix in equilibrium coil exchange which becomes slow on a proton NMR time scale. While d(GGATATCC) fits a two-site exchange model, d(GGm6ATATCC) does not and we invoke the presence of a third species which may be an intermediate in helix formation. NMR and ultraviolet spectroscopy show that methylation destabilizes the helix, measured by the melting temperature and enthalpy of dissociation. PMID- 4043090 TI - Mouse teratocarcinoma and embryonic development. Two-dimensional protein patterns in nerve differentiation. AB - The transition in mouse teratocarcinomas of pluripotential stem cells to histogenetically determined ones of the neurogenic cell lineage was analysed at the total cellular protein level by two-dimensional gel electrophoresis. The change in morphology and function was found to be reflected by extensive shifts in the protein synthesis patterns. From a total of about 1000 resolved polypeptides that are synthesized in embryoid bodies of a multidifferentiating teratocarcinoma, about 12% (117 proteins) are not found or only present at a very much reduced level in two teratocarcinoma-derived neuroblastomas. On the other hand, the change in phenotype is accompanied by the de novo or greatly enhanced synthesis of another 69 proteins (about 7%) in the neurogenic tumors. In a screening for differentiation-specific proteins this set was compared with the protein synthesized in neural tissue of maturing brain and muscle tissue of developing limbs at three different postimplantation stages covering the onset of organogenesis. This comparison disclosed that a great portion of the differentiation-related proteins (26 proteins) are synthesized in both brain and muscle and are probably required by a differentiated cell in general like cytostructural proteins. Seventeen polypeptides, however, are synthesized in a cell type specific manner. In particular, 4 proteins that are synthesized in both neurogenic tumors and in brain but not in muscle tissue were tentatively called nerve-specific proteins (NSP) and are the most promising in further analyses of differentiation-specific proteins. PMID- 4043091 TI - Mouse teratocarcinoma and embryonic development. Two-dimensional protein patterns in muscle differentiation. AB - Muscle cell differentiation was analysed by two-dimensional gel electrophoresis of newly synthesized proteins compared in two parallel systems: in mouse teratocarcinoma-derived tumors that became restricted in their developmental potential to the formation of muscle-like cells and in developing limbs of the early mouse fetus. Muscle cell differentiation in teratocarcinomas was found to be reflected by both a marked decrease in the rate of synthesis of about 12% (119 proteins) of the resolved polypeptides and a pronounced increase in the synthesis of another large set of proteins (83 proteins). The majority of the newly acquired proteins (46 proteins) were also detected in fetal brain and muscle tissue. These proteins are considered to be those which accompany differentiation in general, regardless of cell type, as e.g. ubiquitously occurring structural proteins. Their expression in the muscle cells of the tumors may reflect the normal aspect of this particular differentiation pathway. Five polypeptides were found to appear specifically in both myogenic tumors and developing limbs, but not during brain formation and were tentatively termed muscle-specific proteins (MSP). The identification of differentiation-related proteins in muscle development will allow us to analyse differentiation in early development in molecular terms. PMID- 4043092 TI - Restriction of docking protein to the rough endoplasmic reticulum: immunocytochemical localization in rat liver. AB - Docking protein (or SRP receptor) is an integral membrane protein essential for translocation of nascent polypeptides across the membrane of the endoplasmic reticulum (ER). Anti-docking protein antibodies were used to localize this protein in situ in thin frozen sections using protein A-gold detection methods. The majority of gold particles was restricted to ribosome-studded membranes, whereas particles were rarely seen in areas rich in smooth ER. Quantitative evaluation of labeling suggests that there is one molecule of docking protein for roughly 10 to 20 bound ribosomes. On the basis of these results we conclude that docking protein is the first functionally-characterized integral marker protein specific for the rough membranes of ER. PMID- 4043094 TI - Rapid and sensitive assays for phagosomal acidification in Paramecium and Tetrahymena. AB - Biochemical and cytochemical procedures were developed to measure the rate of phagosomal acidification for phagosomal pH ranging from 5 to 2.5. These assays were based on the pH-dependent inactivation with time of horseradish peroxidase (HRP) activity, a result attributable to the dissociation of this enzyme to a colorless protein and ferriprotoporphyrin in acidic solutions. When preincubated in buffers of varying pH, the rate of HRP inactivation followed a sigmoid curve, with the highest rate of inactivation between 4.3 and 3.5 when using citrate phosphate buffer and between pH 3.4 and 2.8 when using the universal ABC buffer. This inactivation was temperature but not concentration dependent. When Paramecium caudatum, members of the P. aurelia complex or Tetrahymena thermophila was pulsed briefly with HRP and small fluorescent beads, the loss of HRP activity, measured biochemically in cell homogenates and/or cytochemically in phagosomes, was rapid and followed the kinetics of a first-order rate reaction. Both assays gave similar values for the rate constant for acidification and similar rates of inhibition when P. caudatum was exposed to a proton ionophore, carbonyl cyanide p-trifluoromethoxyphenyl hydrazone. These assays can readily be adapted to other phagocytic cells as long as a rapid procedure is available for removing all unphagocytosed HRP and latex beads. These procedures are sensitive and rapid thus allowing many samples to be quickly prepared and analyzed. PMID- 4043093 TI - Fibrinogen distribution on surfaces and in organelles of ADP stimulated human blood platelets. AB - The fibrinogen distribution in platelet organelles after ADP-stimulation was investigated with anti-human fibrinogen using protein A-gold applied to serial sections. Fibrinogen was detected in the so-called alpha-granules of platelets and also in granule protrusions which were observed after ADP-stimulation. The ends of these protrusions were formed as coated membranes and the tips were often in apposition to the surface connected membranes or the plasmalemma. At such places fusion events and hence signs of an exocytosis could be demonstrated by means of cryofixation and cryosubstitution. Examination of serial sections revealed fibrinogen on all these granule profiles. Surface connected membranes, free surfaces and the characteristic structure of the contact zones of aggregated platelets were also labelled by gold particles but less than anticipated. On the platelet surfaces and surface connected membranes fibrinogen was rarely demonstrable with ferritin-labelled anti-human fibrinogen on washed or thrombin stimulated, almost fibrinogen free platelets. After addition of human fibrinogen to the thrombin stimulated and disaggregated platelets a part of the platelets aggregated spontaneously and formed characteristic contact zones. Anti-human fibrinogen was observed on the free surfaces, in filamentous bridges between the contact spaces and in a tubular surface connected membrane system with involvement of coated membranes at the central ends of these structures. The results indicate the following: all alpha-granules contain fibrinogen; after ADP stimulation secretion takes place with involvement of coated membranes; during aggregation fibrinogen binds to platelet surfaces and forms contact spaces; fibrinogen is taken up by the surface connected system with involvement of coated membranes. PMID- 4043095 TI - Duration of symptoms and the effects of a more aggressive surgical policy: two factors affecting prognosis of infective endocarditis. AB - One hundred and six patients were analysed in order to assess the effect of a more aggressive surgical policy in relation to the delays in diagnosis of infective endocarditis. The average duration of symptoms before diagnosis was 9.7 weeks, even though the patients had sought medical advice at a relatively early stage of their illness (2.2 weeks). Three of the 29 (10.3%) patients who were treated surgically died and all three were operated upon five weeks or later after diagnosis. Seventy-seven patients did not have surgery and 15 died (19.5%). The outcome of surgical treatment for prosthetic valve endocarditis was no worse than for native valve endocarditis. The mortality of prosthetic valve endocarditis including early infections was 32% with medical but only 10% with surgical management compared with 14.5% and 10.5% in native valve endocarditis. Endocarditis cannot always be prevented but earlier diagnosis would reduce mortality and prevent complications. When medical treatment is failing then surgery should be considered early and urgently particularly in staphylococcal infection or when large mobile vegetations are recognized; surgery is mandatory in fungal endocarditis. Earlier diagnosis would greatly reduce the current high incidence of surgery, but that depends on a much heightened index of suspicion amongst both general practitioners and hospital physicians. PMID- 4043096 TI - Coronary angiography with flashing tomosynthesis. AB - Thirty-four patients with coronary artery disease were studied with standard 35 mm coronary cineangiography and flashing tomosynthesis, to assess the value of the latter technique to detect stenotic coronary arteries. All occluded vessels and all coronary stenoses seen by cineangiography were also found by flashing tomosynthesis. A correlation coefficient of r = 0.85 (P less than 0.001) was determined between the degrees of stenosis obtained by the two techniques. With flashing tomosynthesis, less contrast medium was needed, the investigation time was shorter, and the radiation exposure markedly reduced. At present, dynamic events, such as collateral blood flow, cannot be evaluated. We conclude that coronary arterial stenoses and occlusions can be reliably evaluated by flashing tomosynthesis. Further technological developments are necessary for the technique to gain clinical acceptance. PMID- 4043097 TI - Malignant ventricular tachyarrhythmias in association with propafenone treatment. AB - During treatment with the class Ic antiarrhythmic agent propafenone, the drug appeared to cause malignant ventricular tachyarrhythmias in five patients. Sudden cardiac death occurred in two of them. Three patients exhibited a transition from non-self-terminating ventricular tachycardia to ventricular fibrillation. In the other two patients electrocardiography during syncope revealed ventricular fibrillation. The observed malignant arrhythmias occurred within the first three days of treatment for chronic complex ventricular ectopic activity. Two of the five patients had markedly impaired left ventricular function. All patients received digoxin and low dose diuretic therapy. In contrast to drug induced arrhythmias encountered with other type I antiarrhythmic agents, the proarrhythmic effects of propafenone were not associated with marked QT prolongation. QRS duration was only slightly affected. PMID- 4043098 TI - Diurnal variation in symptom-limited exercise test responses six weeks after myocardial infarction. AB - Diurnal variation of exercise test responses occurring during symptom-limited treadmill exercise testing was investigated in 45 patients six weeks after myocardial infarction. Each patient was exercised using a Naughton protocol before 8 a.m. and after 6 p.m. on the same day. No complications arose. There was no significant diurnal variation of any of the analysed exercise induced ischaemic abnormalities (angina pectoris or ST segment shift) or of the mean maximal exercise durations and achieved workloads. Mean maximal heart rates and heart rate-systolic blood pressure double products were similar in both tests. ST segment depression occurred in 21 patients and was totally consistent in both tests. An abnormal blood pressure response occurred in 14 patients in the morning test and in 18 patients in the evening test but this discordance did not reach statistical significance. Similarly there was no significant diurnal variation in exercise induced ventricular arrhythmias, although only three of the 11 patients in whom they occurred had this abnormality on both tests. We conclude that in this group of patients, no significant diurnal variation was observed in either exercise induced ischaemic abnormalities or in exercise haemodynamics during symptom-limited exercise tests performed six weeks after myocardial infarction. These data increase the confidence in clinical management decisions based on the results of this test. PMID- 4043099 TI - Prognosis of patients with different peak serum creatine kinase levels after first myocardial infarction. AB - The extent to which patients with low peak serum creatine kinase (CK) at their first myocardial infarction differ from patients with high CK levels in terms of risk for subsequent ischaemic events was investigated in 266 patients who survived the first 48 h from the onset of infarction. All patients were followed up for one year. Four groups were formed based on peak CK less than or equal to 200, 201-400, 401-800 and greater than 800 IU l-1. During follow-up the incidence of mortality was 15% (N = 39), non-fatal re-infarction 9% (N = 23), and angina 53% (N = 140). Hospital mortality was significantly higher (P less than 0.02) in the highest CK-group (16%), but the incidence of non-fatal re-infarction, angina pectoris and late mortality was similar in the four groups. In hospital survivors, ischaemic ST-changes during pre-discharge symptom limited bicycle stress test and multiple vessel disease were equally distributed in all four groups. We conclude that while hospital mortality is directly related to peak CK, there is no relationship between peak CK and late mortality, non-fatal re infarctions, or recurrent angina. Accordingly, diagnostic and therapeutic procedures in the individual patients are not influenced by the amount of serum CK released during acute infarction. PMID- 4043100 TI - Role of blood pressure response to provocative tests in the prediction of hypertension in adolescents. AB - To assess the value of exercise stress testing and of mental stress as predictors of hypertension, we studied 130 normotensive males 14-18 years of age. Sixty-five had at least one hypertensive parent (SHT), while 65 had normotensive parents (SNT). Systolic (SBP) and diastolic (DBP) blood pressure, rate-pressure product (RPP) and 12-lead ECG were recorded at rest, throughout the tests and during the recovery phase. The two groups were not significantly different at rest for the examined variables. However, the SHT group showed a greater average SBP than the SNT group (198.4 +/- 18.7 vs 189.5 +/- 14.9 mmHg; P less than 0.05) at the peak of exercise. A significantly higher proportion of SHT subjects (40.0% vs 18.5%: P less than 0.01) had SBP greater than 200 mmHg. No difference in the ECG pattern between the two groups was observed. During mental stress, no significant differences in the examined variables between the two groups were noted, although SBP, DBP, HR and RPP were slightly higher in SHT than in SNT subjects. These data suggest that the SBP response to dynamic exercise may be a good predictor of hypertension in subjects at risk. PMID- 4043101 TI - Conversion of supraventricular arrhythmias to sinus rhythm using flecainide. AB - We evaluated the efficacy of flecainide acetate (given intravenously to a maximal dose of 2 mg kg-1 and then orally in a dose of 100 mg b.d. or 100 mg t.d.s.) in the conversion to sinus rhythm of 50 patients exhibiting supraventricular arrhythmias (39 with atrial fibrillation, 6 with atrial flutter, 4 with supraventricular tachycardia and one with supraventricular tachycardia in association with the Wolff-Parkinson-White syndrome). Conversion was achieved in 36 patients (72%) (29 cases with atrial fibrillation, 4 cases with supraventricular tachycardia, 2 cases with atrial flutter and one case with Wolff Parkinson-White syndrome), over a mean period of 7.4 +/- 9 h. The patients in which conversion was achieved had arrhythmias which had been in existence for a shorter time (5.3 +/- 9.8 days) than those in which conversion was not achieved (16.7 +/- 26.2 days) (P less than 0.01). The mean dosage of flecainide used to achieve conversion was 2.5 +/- 2.36 mg kg-1. Flecainide appears to be an effective agent for the conversion to sinus rhythm of atrial fibrillation and supraventricular tachycardias. Its efficacy in cases of atrial flutter has not yet been demonstrated. PMID- 4043102 TI - Cardiomyopathy in phaeochromocytoma: report of a case with a 16-year follow-up after surgery and review of the literature. AB - A 39-year-old woman had suffered from congestive heart failure of unknown cause for 3.5 years before a phaeochromocytoma was diagnosed. After pretreatment with phenoxybenzamine, the tumour was removed by surgery resulting in disappearance of signs of heart disease. The patient was followed for 16 years: at that time she was free of symptoms and X-ray and echocardiography showed only a slightly enlarged heart and a minor impairment of left ventricular performance. Six similar cases from the literature are reviewed. The significance of catecholamines in causing heart disease in patients with phaeochromocytoma is discussed. PMID- 4043103 TI - Anomalous left coronary artery from the pulmonary artery presenting with infective endocarditis in an adult. AB - A case is presented of a 36-year old female who presented with signs of mitral regurgitation due to infective endocarditis. Investigation revealed an anomolous left coronary artery arising from pulmonary artery. She successfully underwent mitral valve replacement. Survival following mitral valve replacement and presentation with endocarditis have never been reported in this rare condition. PMID- 4043104 TI - Anomalous origin of an accessory coronary artery from the main pulmonary artery: report of a case with arrhythmia, precordial pain and left heart failure. AB - Anomalous origin of the coronary arteries from the main pulmonary artery is a rare congenital malformation. While this anomaly rarely produces cardiac symptoms, the more frequently encountered anomalous left coronary artery arising from the main pulmonary artery is poorly tolerated, the majority of patients dying in infancy. This report describes a symptomatic sixty-year old man with anomalous posterior descending coronary artery arising from the pulmonary trunk and details the angiographic findings. PMID- 4043105 TI - Diagnosis of left coronary arteriovenous fistula by cross-sectional echocardiography. PMID- 4043106 TI - Prognostic significance of repetitive ventricular response in chronic coronary artery disease. AB - A prospective study was conducted in 267 patients with angiographically defined coronary artery disease without documented ventricular tachycardia to determine the prognostic significance of repetitive ventricular response (RVR) after programmed electrical stimulation (PES). The patients were classified inducible if RVR with 3 or more echo beats (RVR greater than or equal to 3) could be induced. 89 patients without previous myocardial infarction (MI), 61 survivors of MI occurring between 6 weeks and 3 months before and 117 patients who had survived longer than 3 months after MI were studied. A standardized stimulation protocol with single (S1S2) and double (S1S2S3) extrastimuli during ventricular drive at a cycle length of 600, 500 and 430 ms with a current strength below 5 mA at the right ventricular apex was employed. Ventricular responses with 3 to 5 echo beats (RVR3-5) and with 6 and more echo beats (RVR greater than or equal to 6) were distinguished. In 68 (25%) patients RVR3-5 and in 38 (14%) patients RVR greater than or equal to 6 was observed; in 11 patients with RVR greater than or equal to 6 sustained VT was initiated which was monomorphic in 5 of them. The occurrence of RVR greater than or equal to 6 was related to the time interval to prior MI and most frequently found within 3 months of MI. A higher incidence of RVR greater than or equal to 6 was observed in more advanced CAD, although the angiographic findings were unable to predict the results of PES. During a mean follow up of 20 months 11 patients died, 8 suddenly, 3 in cardiac failure. Those who died had more extensive CAD, RVR greater than or equal to 3 was found in 4 of them and nonsustained VT in one. The sensitivity of RVR greater than or equal to 3 as a predictor of sudden death (SD) was 36% and the specifity 60%. The predictive value of inducibility of RVR greater than or equal to 3 as indicator of SD was 4% and the predictive value of noninducibility was 98%. It is concluded that in patients with chronic CAD without spontaneous VT, RVR with 3 more echo beats does not identify a predisposition to die suddenly. PMID- 4043107 TI - Electrophysiology of normal anterograde atrio-ventricular conduction with and without autonomic blockade. AB - The electrophysiological measures of atrio-ventricular (A-V) conduction were investigated in 20 normal subjects (mean age: 43.9 +/- 15.7 years) both during basal state and after pharmacological autonomic blockade. In the basal state A-H and H-V intervals and H wave duration ranged from 55-110 ms (mean 83 +/- 15.9), 35-45 ms (mean 39.5 +/- 3.9) and 10-20 ms (mean 17 +/- 4.1), respectively. The lowest atrial rate inducing Wenckebach periods ranged from 150-200 beats min-1 (mean 176.5 +/- 13.8). The effective refractory period (ERP) and the functional refractory period from FRP) of the atrium ranged from 160-260 ms (mean 211 +/- 26.7) and 210-280 ms (mean 252.5 +/- 21.2), respectively. The ERP and the FRP of the A-V node were in the ranges 230-310 ms (mean 269.3 +/- 27.2) and 330-450 ms (mean 395 +/- 41.2), respectively. After autonomic blockade the H-V interval and the H wave duration did not change in any subject. The A-H interval was in the range 55-105 ms (mean 82.5 +/- 15) and the lowest atrial rate inducing Wenckebach periods 150-220 beats min-1 (mean 179.5 +/- 13.5). The ERP and the FRP of the atrium ranged from 170-270 ms (mean 215.5 +/- 28.3) and 210-300 ms (mean 254 +/- 27.2), respectively. The ERP and the FRP of the A-V node were in the ranges 220 320 ms (mean 260.8 +/- 32) and 330-440 ms (mean 383.3 +/- 43.7), respectively. The A-V node variables did not change significantly following autonomic blockade. These data indicate that: the definition of normal values of A-V node measurements after autonomic blockade allow us to evaluate the role of the autonomic nervous system in the patients with A-V node conduction disturbances; in the basal state the normal values of A-V conduction variables we obtained, of refractory periods in particular, are shorter than those previously reported; this appears to be related to the strict criteria we used in subject selection. PMID- 4043108 TI - Leydig-cell tumor of the ovary: visualization using 131I-19-iodocholesterol scintigraphy. AB - A Leydig (Hilus)-cell tumor of the ovary was diagnosed in a 54-year-old woman with severe hirsutism and virilization. This case is unique in that it was diagnosed in a postmenopausal female 24 years after ovarian irradiation for sterilization, and the tumor was successfully localized preoperatively using 131I 19-iodocholesterol scintigraphy. This nuclear scanning technique may be of use in documenting the biologic activity of ovarian masses and in localizing functioning ovarian tumors which are too small to palpate or to localize by other means. PMID- 4043109 TI - Evaluation of methods for qualitative and quantitative assessment of esophageal transit of liquid. AB - The aim of this work was to compare the advantages and the limitations of several data processing techniques for the assessment of esophageal transit. The following qualitative methods were evaluated: scintigraphic image, cine-display, regional time-activity curve, and condensed image. The quantitative methods evaluated were the pixel to pixel presentation of parameters of the time-activity curves such as time of arrival, time to maximum, and several downslope parameters, mean transit time, mean time, and a new transit parameter based on the radioactive decay. The study allowed us to conclude that for the detection and the quantitation of esophageal transit the method of choice was the combined use of the condensed image and the pixel to pixel mean time image. The parametric image using the transit parameter calculated from decay was shown as a valuable alternative if an ultra-short half-life radionuclide was used as the tracer. PMID- 4043110 TI - Radionuclide imaging of ovarian tumours with a radiolabelled (123I) monoclonal antibody (NDOG2). AB - The biodistribution of a radiolabelled monoclonal antibody (123I-NDOG2) was studied in patients with ovarian tumour. It was found that the uptake patterns in known tumour sites was variable and that the clearance of the agent from the vascular pool was due to renal excretion of the radionuclide and the redistribution of the radioactively labelled compound into other compartments. The mean (+/- SD) plasma clearance time was 20.8 (+/- 2.3) h and the ratios of target (tumour) to background (thigh) ranged between 1.4 and 4.8. The ratio between the plasma radioactivity at either 3.5 or 20 h after administration was calculated relative to the initial plasma radioactivity. These values (0.79 and 0.48, respectively) were incorporated into an image-subtraction technique that allowed for redistribution outside the vascular pool. A whole-body dose equivalent to 16.3 mu Sv MBq-1 (60.4 mrem.mCi-1) was calculated. PMID- 4043111 TI - Serial measurement of renal plasma flow. AB - Effective renal plasma flow was measured two or three times in 1 h in 12 healthy volunteers. Radiohippuran (ortho-iodohippurate) was injected intravenously, and blood samples were obtained 8, 13 and 18 min post-administration. The problem of interference in succeeding measurements by activity from preceding injections was overcome by the use of three different radiolabels. These were, in order of use, 125I, 123I and 131I. The principal energies of gamma- and/or X-ray emission were 30, 160 and 365 KeV, respectively, allowing completely independent assay. A close correlation was observed between the results obtained for the three radionuclides over a wide range of renal plasma flow. The technique is relatively non-invasive and is presented as a suitable method for the important task of measuring renal plasma flow under the influence of drugs, especially of anaesthetics. PMID- 4043112 TI - Intracranial meningioma with abnormal localization of bone-seeking radiopharmaceutical: correlation with gross and microscopic pathology. AB - Meningioma is one of the neoplasms in which there may be extraosseous localization of bone-seeking radiopharmaceuticals. Tumor calcification, calvarial erosion, and the formation of reactive bone have been proposed as the cause of this abnormal tracer localization. We present a patient with a frontal meningioma that was evaluated using 99mTc-methylene-diphosphonate bone scintigraphy, head computed tomography, and skull radiography; the homogeneous density seen in the radiographic studies corresponded to the area of bone-seeking-agent localization shown in the scintigram. At autopsy, bony tissue and a few psammoma bodies were found in the meningioma, and apparently accounted for the bone-tracer localization. There was no calvarial erosion and no formation of reactive bone. If skull-radiographic studies show a homogeneous, radio-opaque lesion with no reactive changes in the adjacent skull, a meningioma showing a localization of a bone-seeking radiopharmaceutical may be predicted to have bone-tissue formation with or without psammoma bodies. PMID- 4043114 TI - European Nuclear Medicine Congress. September 3-6, 1985, London, England. Abstracts. PMID- 4043115 TI - Localization of exercise-induced myocardial ischemia with single view and biplanar radionuclide ventriculography: validation in single vessel coronary disease. AB - The ability of single view and biplanar radionuclide ventriculography (RVG) to determine the location of myocardial ischemia during maximal graded supine bicycle exercise was assessed in 50 patients with chest pain, no prior myocardial infarction, and a single coronary stenosis of greater than or equal to 50% luminal diameter narrowing at coronary angiography. A biplane collimator was used so that both right anterior oblique (RAO) gated first-pass and left anterior oblique (LAO) equilibrium RVG could be performed at rest and exercise. Results were compared with those obtained using 4-view 201Tl myocardial scintigraphy in the same patients. Regional wall motion abnormalities (WMA) and 201Tl perfusion defects were detected and assigned to individual coronary vessels by agreement between at least two of three independent observers, who read all studies blinded along with those from control subjects with chest pain but no angiographically significant coronary artery disease. When scintigraphic abnormalities were detected, both biplanar RVG (36/39 = 92%) and 201Tl (25/25 = 100%) were more frequently correct in predicting the stenosed vessel than single view LAO RVG (24/32 = 75%) (P less than 0.05). At RVG only inferior WMA, in the RAO view, predicted right coronary stenosis. Only posterolateral WMA, in the LAO view, predicted left circumflex stenosis. Thus biplanar, but not single view, LAO exercise RVG is a reasonable alternative to exercise 201Tl for localizing exercise-induced ischemic abnormalities to individual coronary stenoses. PMID- 4043113 TI - Scintigraphic demonstration of a diaphragmatic defect as the cause of massive hydrothorax in cirrhosis. AB - A 64-year-old man presented with a massive right-sided hydrothorax associated with cirrhosis of the liver. There was no clinical evidence of ascites nor other underlying disease. The usual complementary tests failed to demonstrate any causative abnormality. Chest and abdominal scintigraphy after intraperitoneal injection of 99mTc-human serum albumin disclosed early filling of the pleural space by the radiopharmaceutical and suggested a diaphragmatic defect as the cause for this rare association. PMID- 4043116 TI - Nuclear medicine liver-function tests for pregnant women and children. 2. A new test method via urine using 15N-methacetin. AB - A simple, non-invasive, non-radioactive liver-function test is proposed. After an oral dose of 3 mg 15N-methacetin per kilogram body mass, the kinetics of 15N excretion via urine were characterized by the quotient of the amounts of 15N excreted in two successive urine samples (Q value). The stable nitrogen isotope 15N was found to be an excellent and easily detectable indicator of the sum of all methacetin metabolites present in urine. Alterations in the nature or ratio of methacetin metabolites due to liver diseases could not be found. From the investigation of 11 men, 3 pregnant women and 15 children, a clear difference was observed in Q values of healthy persons and patients suffering from liver-cell activity diseases. The discriminating power of our new liver-function test is shown to be equivalent to that of the 14CO2 breath test. PMID- 4043117 TI - A liver-function test using 15N-labelled ammonium chloride. AB - Malfunction of the liver involves disturbances of urea synthesis and ammonia detoxification. These phenomena became apparent, especially during ammonia loading of patients. The functional state of the liver can be assessed by oral administration of 15NH4Cl and subsequent analysis of 15N-urea and 15N-ammonia in urine by emission spectrometry. Clinical tests based on the ratio of the excess abundances of 15N-ammonia to 15N-urea excreted in urine 3 h after oral administration gave values for patients with liver disease which differed significantly from those for healthy subjects. Absorption disturbances, which often accompany liver diseases, do not influence the effectiveness of the method. PMID- 4043118 TI - Detection of occult and intermittent rhinorrhea using 111In-DTPA. AB - In an attempt to detect occult or intermittent rhinorrhea, 10 patients without and 9 cases with rhinorrhea were investigated after a lumbal injection of 1.3 mCi 111In-DTPA. Significant count rates were detectable in the nasal pledgets of all individuals, so that it was not possible to distinguish those with and those without rhinorrhea. Therefore, the ratio of activity in nasal pledgets and blood normalized for weight recommended by McKusick et al. was used. In the patients without evidence of rhinorrhea, the ratio did not exceed 2.0, whereas in 8 of the 9 cases with rhinorrhea, it was considerably increased. The detectability of rhinorrhea was increased by using more than one measurement and by provocation manoeuvres. PMID- 4043119 TI - Inquiry to standardize nuclear-medical functional investigations. PMID- 4043120 TI - Scintigraphy of lymphatic vessels in malignant melanoma of the skin before operation (en bloc excision). AB - An injection of 99mTc-labelled antimony sulphide colloid was used to show the lymphatic pathways in patients with malignant melanoma of the trunk skin. Using a gamma camera, optimal visualisation was obtained 15-30 min postinjection. Surprising deviations of the lymphatic pathways were found; therefore, this method makes it possible to plan continuity dissection appropriate to individual cases. Two examples are presented. PMID- 4043121 TI - The prevention of adhesion of 99mTc-tin (II) colloid to glass surfaces. AB - The tin(II) colloid is highly surface active and adheres strongly to glass surfaces. Treating glass with 5% (v/v) dichlorodimethylsilane in toluene causes a significant reduction in the adhesion of the colloid. PMID- 4043122 TI - Cerebral gigantism (Sotos syndrome). Compiled data of 22 cases. Analysis of clinical features, growth and plasma somatomedin. AB - An in depth study on growth, bone age, cranial CT scans and plasma somatomedin activity (SM-act) was made of 22 children with Sotos syndrome. In addition to the known characteristics of the syndrome, thin and brittle nails were found in three adolescent patients. The mean body stature, expressed as standard deviation score, increased from 2.2-2.8 in the 1st year of life, followed by a fall to 2.0 in the 2nd year. Thereafter the SDS increased slowly to values of 3.0 at 10 years of age. At least two subjects have reached an exceptionally tall final stature. After the age of 2 years, delta SDS/year remained very stable (-0.1-0.2), concurring with growth velocities in the upper normal range. Bone age was advanced in all patients. Cranial CT scans showed ventricular widening, mid-line cava and Sylvian anomalies in nine, six, and three patients respectively. SM-act dropped from high or normal values in the 1st year, to below normal from 1-5 years, and returned thereafter to the lower half of normal or below the normal range. PMID- 4043123 TI - Growth in Cushing syndrome. AB - Pre- and post-operative growth was analysed in eight children with Cushing syndrome. Six children had Cushing's disease; three of them were treated by bilateral adrenalectomy and three by transphenoidal pituitary adenectomy. One child had an adrenocortical adenoma and another primary adrenocortical nodular dysplasia. The typical cushingoid habitus was not always present during hypercortisolism. In contrast, abnormal deceleration of longitudinal growth and increase in relative weight were constant. The slowing of growth started 0.2-5.1 years before diagnosis. In four children these changes concurred. In three others the excessive weight gain preceded the slowing of growth, by 2.5-7.0 years. In one patient the deceleration appeared first; this was a girl with concomitant coeliac disease. This pattern of growth change occurring before (normal slowing of growth in) late puberty should raise the possibility of hypercortisolism. There was a suggestion of a better growth recovery in Cushing disease after pituitary adenectomy than after bilateral adrenalectomy. PMID- 4043124 TI - Epilepsy and associated handicaps in a 1 year birth cohort in northern Finland. AB - A 1 year birth cohort in the provinces of Oulu and Lapland in the Northern part of Finland consisted of 12058 live-born infants, this being 96% of all children born in 1966 in this area. Information on morbidity up to the age of 14 years was collected prospectively by means of questionnaires, special examinations and from national and regional registers of hospital admissions and social services contacts. The total number of children with epilepsy, defined as the occurrence of at least one afebrile epileptic seizure, was 208, 113 boys and 95 girls. The cumulative incidences for epilepsy up to the age of 14 years was 17.3 per 1000. Primary generalised epilepsy was present in 63% and partial seizures in 37%. At least one additional handicapping condition, such as cerebral palsy, mental retardation, and visual or auditory defect was present in 74 children (35.5%). Mental retardation was the most frequent additional handicap, being present in 28%, whereas 16% of the children had cerebral palsy. A total of 75% of the children were able to attend an ordinary school. The high frequency of epilepsy in this study, as compared to other studies, is explained by the cumulative registration of the cases and a high degree of ascertainment of cases with epilepsy. PMID- 4043125 TI - Serum zinc and copper levels in children with meningococcal disease. AB - Mean serum zinc and copper levels were depressed in 94 children aged 1 month to 9 years who presented with meningococcal disease. The mean serum zinc level was 44 micrograms/dl (reference value 78 micrograms/dl, SD 18) and the mean serum copper level 157 micrograms/dl (reference value 159 micrograms/dl, SD 27). Nineteen patients had serum zinc levels less than 25 micrograms/dl and ten patients had serum copper levels less than 101 micrograms/dl. Serum zinc levels were significantly lower in patients who were septicaemic or in whom manifestations of severe disease such as shock, more than 20 petechiae, ecchymoses and evidence of disseminated intravascular coagulation occurred compared to those without these features. Serum copper concentrations were higher than reference levels in patients with meningitis and in less severely ill patients. Copper levels were significantly lower in patients with septicaemia, severe disease, shock, more than 20 petechiae, ecchymoses, disseminated intravascular coagulation, leucopenia and patients who died compared with patients without these features. PMID- 4043126 TI - Arrhythmia or myocarditis: a novel clinical form of Legionella pneumophila infection in children without pneumonia. AB - The possibility that L. pneumophila causes cardiac disorders without respiratory or pulmonary symptoms in childhood was investigated. Out of 20 children with cardiac troubles of unknown aetiology, three showed a four-fold antibody increase or fall in titre against L. pneumophila antigens by the IFA test. Two children, aged 7 months and 2.5 years, had self-limiting arrhythmia and a third, 10-year old, was suffering from a severe myocarditis. There was no serologic evidence of concurrent infection by respiratory or coxsackie B viruses nor by M. pneumoniae. It is suggested that Legionella infection should be considered in cardiac diseases in childhood, even if pneumonia is lacking. PMID- 4043127 TI - Hepatitis B vaccination and immune response in children with malignant diseases. AB - Fifty children with malignant diseases were vaccinated against hepatitis B. Twenty-nine children suffered from leukaemia or non-Hodgkin's lymphoma; 14 of these were on intensive chemotherapy (group I) and 15 were without intensive therapy (group II). The other 21 children had various forms of solid tumours, 14 of them were on intensive therapy (group III) and 7 were without intensive therapy (group IV). To evaluate the immune response, we determined antibody titres over a period of more than 14 weeks after the first vaccination. As 22 out of 50 patients had received passive immunisation together with either the first or the first and second vaccination, antibody titres at the 14th and 18th week (i.e. more than 10 weeks after passive immunisation) were used to evaluate the vaccination results. An antibody titre of greater than or equal to 10 mIU/ml was considered to be a positive response. All patients of group IV, but only 4 out of 14 in group III, 4 out of 15 in group II, and 0 out of 14 in group I produced antibody titres higher than 50 mIU/ml. In contrast to the full response in group IV, two-thirds of all other patients had no immune response (less than 10 mIU/ml). Based on our experience we recommend vaccinating patients suffering from solid tumours and receiving no intensive therapy (group IV) against hepatitis B and protecting all the other children with malignant diseases by passive immunisation, if necessary. PMID- 4043128 TI - Biphasic (early and late) asthmatic responses to exercise in children with severe asthma, resident at high altitude. AB - Twenty-three children with severe asthma who had been resident at high altitude for at least 3 months, considerably reduced their requirement for regular anti asthma therapy. On a standard exercise challenge in low humidity, ten had no response, seven had isolated immediate bronchospasm and six had biphasic responses with immediate bronchospasm followed 4-10 h later by a late reaction sustained for at least 2 h. The existence of biphasic responses after exercise, similar to those observed after antigen challenge, supports the concept of mast cell involvement in exercise-induced asthma. PMID- 4043129 TI - Serum immunoreactive trypsin and pancreatic lipase in cystic fibrosis. AB - Serum immunoreactive trypsin (IRT) and pancreatic lipase have been measured in 59 patients with cystic fibrosis (age 1 month-27 years). Follow-up values were obtained from 49 patients. Their serum enzyme levels were compared to those of 120 healthy children of all age groups. Faecal fat excretion was determined in selected patients (n = 23) to elucidate the relationship between serum enzyme levels and pancreatic exocrine function. In cystic fibrosis IRT and lipase showed a very similar age-correlated pattern: in infancy levels were markedly elevated. During the following years the concentrations of both enzymes decreased rapidly and were found to be far below the normal range after the 10th year of life. Elevated enzyme levels in infancy as well as low levels in all age groups coincided with steatorrhea. Older patients (11-27 years) without severe pancreatic insufficiency however, had IRT and lipase levels in or above the normal range. In healthy children there was no age dependency of IRT levels, whereas in the first 12 months of life lipase levels were significantly lower than in later childhood. PMID- 4043130 TI - Inter-laboratory quality control in neonatal screening for inborn errors of metabolism. AB - Screening of neonates for inborn errors of metabolism has been carried out on a national level since 1969 in the Federal Republic of Germany. To raise the reliability of these routine investigations, we introduced an external quality control in March 1982. Every 2 months ten filter paper samples were sent to the screening centres in West Germany. Some of these samples have a normal and others a slightly raised content of phenylalanine, leucine, methionine and galactose. The success of this external quality control is appraised on the basis of the number of false negative results. In the course of time, screening centres in France, Israel, Italy, Japan, Switzerland, Taiwan, Turkey and Yugoslavia have also participated in these inter-laboratory quality controls. PMID- 4043131 TI - Homozygous hypobetalipoproteinaemia and phenylketonuria. AB - Two patients, aged 0.1 and 2 years, with homozygous hypobetalipoproteinaemia, one with PKU in addition are described. The clinical evaluation showed no neurologic abnormalities. Treatment with a fat-reduced, protein and carbohydrate-enriched diet was combined with vitamin A and E supplementation, according to the suggestions for classical abetalipoproteinaemia. In the patient with PKU the protein intake was increased by using a phenylalanine-free, amino acid mixture. Only by this, were normal growth and weight gain achieved. PMID- 4043132 TI - Development of the intestinal flora in very low birth weight infants compared to normal full-term newborns. AB - Development of faecal flora was studied in seven very low birth weight (VLBW) infants, who were fed on human milk and whose birth weights ranged from 810-1350 g. The intestine of the VLBW infants was first colonised by enterobacteria and streptococci, as it was in full-term infants. VLBW infants differed, however, from full-term infants in that both types of organism continued to be predominant for a longer period, and establishment of bifidobacterial flora was retarded. Bifidobacteria first appeared in the stools of VLBW infants at a mean age of 10.6 +/- 2.7 days and became predominant at a mean of 19.8 +/- 8.9 days, in contrast to full-term, breast-fed infants in whom bifidobacterial flora appeared at as early as 4 days of age. The delay seemed to be related to the low milk intake of the VLBW infants. The number of viable staphylococci in the stools of VLBW infants was generally higher than that in full-term infants. Although emergence of Bacteroides, Clostridium and lactobacilli was delayed compared with full-term infants, differences in their occurrence and prevalence between VLBW and full term infants were not remarkable. PMID- 4043133 TI - Anticoagulant therapy by continuous heparin-antithrombin III infusion in newborns with disseminated intravascular coagulation. AB - In ten newborns with severe alteration of the coagulation system due to DIC, AT III concentrate was infused continuously after prior activation with heparin. The rise in AT III activity showed a great variability among the infants and for one child during the course of the therapy. The mean rise of AT III activity by 40 U/kg per day heparin was 8.7%. If AT III concentrate (40 U/kg per day) was activated with 200 U/kg per day heparin, excessive anticoagulation effect was only observed in one child. In four children who had failed to respond to prior heparin therapy, improvement of the coagulation status was achieved within 2 days. PMID- 4043135 TI - Capillary sampling as an alternative to venous sampling for blood culture in neonates. PMID- 4043134 TI - Obstructive sleep apnoea probably related to a foreign body. AB - A 2-year-old child was admitted because of sudden onset of symptoms compatible with obstructive sleep apnoea. Physical examination revealed slightly hypertrophic tonsils. A polygraphic study showed 150 apnoeic episodes of obstructive type during 8 h night sleep. A foreign body consisting of a piece of a celophane candy wrapper was found by surgery. Removal of the foreign body, the adenoids and tonsils resulted in a complete recovery. A second polygraphic study performed 4 months after surgery gave entirely normal results. A foreign body should be considered in the aetiology of obstructive sleep apnoea of sudden onset in children. PMID- 4043136 TI - Aplastic anaemia induced by intravenous phenytoin and lidocaine administration. PMID- 4043137 TI - The importance of the lymphatic system. PMID- 4043138 TI - Prenatal diagnosis of tyrosinaemia type I by use of stable isotope dilution mass spectrometry. PMID- 4043139 TI - Diazepam: kinetic profiles in various brain areas, plasma and erythrocytes after chronic administration in the rat. AB - The regional distribution of diazepam (DZP) was established in eleven discrete brain areas in the rat after i.m. chronic treatment (15 days; 5 mg/kg/day). In addition, the kinetic profiles of this drug were investigated in plasma, eryhtrocytes, and three CNS regions (nucleus caudatus, hippocampus, and cerebellum) upon which the pharmacokinetic study was focused. The modifications occuring in plasma-protein binding and erythrocytes binding were reported. In the CNS, the DZP was rapidly distributed; its concentrations and its kinetic profiles were not uniform in the different brain areas studied. The highest amount of DZP was noted in the hypothalamus, while nucleus caudatus and colliculi also presented important DZP levels. Concerning the kinetic parameters after chronic administration, an increase in the elimination half-life time value in central and peripheral compartments, as compared to values reported after acute administration, was observed. The study of cerebral DZP levels as compared with those in the erythrocytes or in plasma suggests a linear correlation in the three CNS areas investigated. These experimental results demonstrate the interest of such studies for psychotropic drug monitoring. PMID- 4043140 TI - A further study of the pharmacokinetics of gitoxin in rabbit isolated liver: clearance of 3H-gitoxin. AB - Hepatic clearance of 3H-gitoxin was studied in the rabbit using an isolated perfused liver technique with an emulsion of a perfluorocarbon. The liposoluble material in the perfusion medium was extracted with dichloromethane, and gitoxin was assayed in the extract by high performance liquid chromatography. Pharmacokinetic parameters were estimated for the liposoluble (dichloromethane soluble) material in the water phase obtained by centrifugation of the emulsion, for the liposoluble material and unchanged gitoxin in the total emulsion. Distribution and elimination half-lives of the liposoluble fraction in the water phase, were estimated to be 0.47 and 4.80 hours respectively, Vd to be 148 ml.g-1 and intrinsic clearance to be 1.16 ml.min-1.g-1; these parameters were compared with those of a previous study with unlabelled gitoxin. Distribution and elimination half-lives of the liposoluble compounds in the emulsion were estimated to be 0.48 and 4.62 hours, Vd to be 47 ml.g-1 and intrinsic clearance to be 1.07 ml.min-1.g-1; these data were compared with those of the liposoluble compounds in the water phase. Distribution and elimination half-lives of unchanged gitoxin in the emulsion were estimated to be 0.22 and 0.70 hour, Vd to be 59 ml.g-1 and intrinsic clearance to be 11.4 ml.min-1.g-1; these data were compared with those of the liposoluble compounds in the emulsion. The subcellular distribution of gitoxin and its metabolites in the liver indicated that 79% of the radioactivity was found in the soluble fraction, no significant binding occurring in the mitochondrial and microsomal fractions. PMID- 4043141 TI - Pharmacokinetics of dipyrone in man; role of the administration route. AB - Pharmacokinetics of dipyrone, an aminopyrine derivative and potent analgesic, were studied in human following cross-over oral (p.o.) and intravenous (i.v.) administration of single one g doses to 6 subjects. High-performance liquid chromatographic (HPLC) methods were used to follow the drug and its active metabolite, 4-monomethylaminoantipyrine (MAA) in plasma and urine of subjects. Following p.o. doses, no unchanged dipyrone was detectable in plasma and urine. MAA appeared in plasma no later than 0.5 h after oral doses and reached its maximum concentration (7.52-22.69 micrograms/ml) in 1-2 h. Pharmacokinetic characteristics of MAA indicated a two and a one-compartment open model after i.v. and p.o. administration, respectively. Elimination half-life of MAA was found to be independent of the route of administration and ranged from 1.60 to 3.67 h. Although no significant difference was noticed between the area under plasma MAA concentration-time curves, 2.2-7.5 folds higher MAA was found unchanged in urine following i.v. administration (34.41-158.38 mg) as compared to the oral route (9.56-43.92 mg). It is suggested that after oral administration, dipyrone is rapidly and to a great extent converted to MAA during the first pass through the gut and/or liver before reaching the systemic circulations. Following i.v. administration, on the other hand, a relatively slower process of dipyrone conversion may allow a significant renal excretion of dipyrone which, in turn, is converted to MAA in the kidney and/or urine thereby giving rise to a significantly higher MAA in urine. PMID- 4043143 TI - Disposition and pharmacokinetics of cadralazine and individual metabolites in man. AB - The absorption, biotransformation and elimination of the antihypertensive drug cadralazine, 2-(3-[6-(2-hydroxypropyl)ethylamino]pyridazinyl)-ethylcarbazate , have been studied in two healthy male volunteers, following single 20 mg oral doses of the 14C-labelled preparation. Absorption was rapid and complete. In plasma total 14C-compounds reached maximum levels of 395 and 312 ng/g after 0.5 and 1.5 h in subject A and B, respectively. The levels rapidly declined to 3 and 6 ng/g after 24 h. Unchanged cadralazine constituted the major fraction, 72%, of the integrated plasma concentration (AUC, 0-24 h) of total radioactivity. As determined by an isotope dilution technique, about 1% of the AUC of plasma-14C was attributable to a pharmacologically active hydrazino-metabolite (IV) formed by decarbethoxylation and 2% to the acetylation product of the latter (V). Excretion of the radioactivity occured predominantly by the kidneys, 91 and 94% within 0-24 h in subject A and B. After 96 h 94 and 99% of the dose were found in the excreta. In the 0-48 h urine 73% of total 14C consisted of unchanged drug. The hydrazino-metabolite (IV) accounted for about 2% of urinary radioactivity, and two secondary products of the same pathway (II, V) for another 2%. Products of N-dealkylation (VI, VII) and C-oxidation (VIII) constituted together another 5%. PMID- 4043142 TI - Bioavailability and elimination kinetics of the combination furosemide retard/triamterene. AB - In a pharmacokinetic study on 18 healthy male volunteers the bioavailability and elimination kinetics of furosemide-retard and the combination furosemide retard/triamterene were investigated and compared with the non-retarded form and another retard form of furosemide. The relative bioavailability of the non retarded form of furosemide was distinctly reduced by the retardation in the substances investigated. It varied between 42-66% in the plasma and between 37 73% in the urine. In the combination with triamterene the serum concentration time curve of furosemide was only slightly modified but the renal excretion of furosemide was more influenced (36% for furosemide-retard and 25% for furosemide retard/triamterene). In comparison, the values for the renal excretion of triamterene and OH-TA sulfate were distinctly greater than those obtained after administration of triamterene alone. A renewed increase of the plasma concentration and renal excretion of furosemide were observed between 9 and 10.5 h after administration of furosemide-retard/triamterene. This observation suggests that a further absorption of furosemide occurs as a consequence of the delayed release from distal parts of the small intestine or from the large intestine. PMID- 4043144 TI - Pharmacokinetics and metabolism of tomoxiprole, a new analgesic antiinflammatory agent, in the rat. AB - The pharmacokinetics and the metabolic profile of tomoxiprole, a new analgesic antiinflammatory agent belonging to the class of 3-alkyl-2-aryl-3H-naphth (1,2 d)imidazoles, were studied in the rat. After oral administration (5 mg/kg) to male rats, tomoxiprole was rapidly absorbed, mostly by the gut, and reached maximum plasma levels of about 0.5 microgram/ml in 0.25-2 h. A metabolic first pass reduced the extent of oral bioavailability of the parent compound to about half, while absorption (total 14C data) was estimated to be complete. After intravenous injection (2.5 mg/kg), the plasma kinetics of tomoxiprole in male rats showed a bi-exponential profile, and the terminal elimination half-life was 4.2 h. The apparent volume of distribution was high, suggesting a wide distribution of the drug. Increasing the oral dose by ten times (50 mg/kg), resulted in linear kinetics with a proportional increase of the C max and AUC values and the same value of terminal elimination half-life. In females given a 5 mg/kg dose, the plasma levels of 14C, tomoxiprole and AUC values were somewhat higher than in males. The plasma levels of total 14C after iv or po treatments were higher and more sustained than those of tomoxiprole. The kinetic profile after iv administration was described by a three exponential terms equation and the terminal elimination half-life was 38.7 h. Upon iv administration, total 14C was rapidly distributed in highly vascularized tissues while in others, like the bone, fat, gonads, pancreas and skin the equilibrium with the central compartment was attained later. Target organs were the adrenals, liver, lungs, pancreas, thyroid, stomach and above all the fat tissue. Elimination from tissues was almost complete 48 h after the treatment. 14C was eliminated mainly in the feces (80% of dose) as metabolites. In the bile, five polar metabolites were detected; one of them, desmethyl tomoxiprole glucuronide, accounting alone for more than 80% of the total biliary radioactivity; was purified and its structure assigned. PMID- 4043145 TI - Absorption, tissue distribution, and excretion of 3H-labeled arbaprostil in the male rat. AB - A single dose of arbaprostil-11 beta-3H (4 micrograms/kg) was administered orally to male rats. A maximum plasma radioactivity concentration equivalent to 2.5 to 2.8 nanograms of the prostaglandin per ml was reached at 30 minutes and was maintained until 120 minutes after drug administration. The plasma drug disappearance half-life was 2.6 hours. These results along with data from tissue distribution studies suggested a rapid uptake of radiolabeled arbaprostil by the glandular stomach tissue followed by an apparent zero-order release of drug related radioactivity from this tissue "reservoir" into the plasma. Drug-related radioactivity was excreted rapidly, with 96 to 99% of the urinary excretion and 82 to 97% of the fecal excretion being completed within 24 hours. A total of 49.6 +/- 3.5% of the orally administered dose was excreted in the urine and 46.7 +/- 3.9% in the feces. No radioactive residues were detected in the animals at the end of the 120 hour specimen collection period. The metabolic stability of the 11 beta-tritium label and the suitability of arbaprostil-3H for use in human studies was demonstrated. PMID- 4043146 TI - Progressive dementia with motor neuron disease. An additional case report and neuropathological review of 20 cases in Japan. AB - A 68-year-old male had the characteristic clinical features of progressive dementia accompanied by motor neuron disease. The duration of his illness was 26 months. The chief findings from light microscopic studies were: diffue neuronal degeneration characterized by a simple atrophy and a mild disappearance of nerve cells throughout the CNS. Status spongiosus was observed in the basal ganglia. There were lesions similar to those of a motor neuron disease in the brain stem and spinal cord. Although there were no clinical symptoms of an extrapyramidal disease, severe involvement was seen in the substantia nigra. This patient belongs to the same group of cases of presenile dementia with motor neuron disease described by the author. A neuropathological review of 20 similar cases reported in Japan is discussed and the possibility of a new disease entity for these cases is suggested. PMID- 4043147 TI - Childhood experiences of endogenous and neurotic depressives. AB - The parent-child relationship, the relationship between the parents, and the contact of the child with the outside world was investigated on the basis of retrospective interview data concerning the childhood of endogenous and neurotic depressives and a nonclinical control group. A number of significant links between childhood experiences and the various forms of depression emerges. PMID- 4043148 TI - Does outpatient treatment reduce hospital stay in schizophrenics? AB - The implementation of community mental health care for psychiatric patients in Mannheim, an industrial city of approximately 300,000 inhabitants, poses questions concerning the impact of outpatient treatment on the probability of rehospitalization. For this purpose the use of extramural facilities by a group of 148 patients with a diagnosis of schizophrenia was studied over a period of 18 months. Based on a model of utilization that allows for the removal of confounding effects the statistical analysis reveals that outpatient contacts with psychiatrists in practice or with an outpatient clinic indeed reduces time in hospital and also improves the psychopathological status of the patients. PMID- 4043149 TI - Neuropsychological and neuroendocrinological disturbances associated with extracerebral cysts of the anterior and middle cranial fossa. AB - In ten adult patients various clinical signs and symptoms led to the diagnosis of an arachnoid cyst in the anterior and middle cranial fossa. In this study a functional relationship between these cysts and disturbances of higher cognitive processes is described. In addition, neuroendocrinological impairment were caused by arachnoid cysts reaching into the suprasellar cistern. Considering the short medical history of our patients we presumed the disturbances not to be primary, but rather secondary, caused by an expansion of the cysts' volume. PMID- 4043150 TI - AMP-rated psychopathology in chronic alcoholics. AB - In a group of 39 alcoholics within a withdrawal process, the psychical situation was rated using AMP scales (Angst et al. 1969). Cluster analysis of the items rendered the following five-cluster solution: (1) "aggressive-depressive" patients, (2) "less impaired" persons, (3) "slowed persons with diminished contact", (4) "emotionally inadequate" persons, (5) "appealing depressive" persons. These results are discussed with respect to other data from clinical history and diagnostic findings. PMID- 4043151 TI - Phantom phenomena (phantom arm) following cervical root avulsion. Effect of dorsal root entry zone thermocoagulation. AB - We report on nine male patients with cervical root avulsions and brachial plexus injuries following traffic accidents. These non-amputees (mean age 33.7 years) had a phantom arm beside the paralysed arm. Cervical root avulsions were demonstrated either by myelography or surgically. Mostly the roots C5-Th1 were affected. Eight of the nine patients had Horner's syndrome on the side of the root avulsion. The phantom arm appeared immediately after the accident, except in one patient who was symptom-free for 2 weeks. In two cases the phantom arm disappeared spontaneously. Four patients underwent a DREZ lesion. After surgery the phantom arm disappeared, and three of the patients became painfree, while one patient experienced pain relief of 20% to 50%. Reviewing the literature it is assumed that phantom limb following injury to the brachial plexus indicates cervical root avulsion. In such cases Horner's syndrome is a good indication for lower cervical root avulsion (C8-Th2). PMID- 4043152 TI - Electron microscopic assessment of bile regurgitation of humans in extrahepatic obstructive jaundice. AB - Thirty-seven patients were studied on the anatomic routes of bile regurgitation into the blood stream by electron microscopy. The aim was to identify the relationship between the clinical results and pathway of bile regurgitation. These patients were classified into 3 groups; recovered, delayed, and fatal. Transcellular, paracellular, direct communication, necrotic hepatocyte and ruptured ductule pathway were found. In the recovered group, the transcellular pathway was most frequent with an incidence of 54.17%, and a direct communication pathway was found to be 54.55% in the fatal group with a significant difference between that of the recovered and delayed group. Long-duration bile duct obstruction creates bile regurgitation by way of direct communication between the canaliculi and Disse's space, and usually with a poor prognosis, since the serum bilirubin reached the high level of 22.65 mg%. Therefore, it is better to relieve the intrabiliary pressure as early as possible to prevent the jaundice from producing the irreversible change of hepatic canaliculi and Disse's space. PMID- 4043153 TI - Monocyte function following surgery in man. Increased numbers and stimulation of migration, phagocytosis and chemiluminescence following abdominal surgery. AB - The whole blood monocyte count (WBMC), migratory response (MMR), phagocytosis (MPI), chemiluminescence (MCL) and serum opsonic activity (SOA) were measured in patients undergoing elective surgery. The WBMC, MMR, MPI and MCL increased significantly at 24 h after operation in patients undergoing abdominal surgery with a moderate fall at 48 h and a return to normal values at 1 week; the SOA was little altered. In patients undergoing minor surgery the WBMC was also increased after surgery but the MMR was unchanged. The finding that certain monocyte functions are increased after surgery contrasts with studies showing that reticulo-endothelial clearance is depressed in the post-operative period. PMID- 4043154 TI - Peroperative myocardial ischemia and citrate administration: cardiovascular adaptability in conscious dogs. AB - Since the hemodynamic response elicited by the administration of citrate is sensitive to alterations in the baseline cardiovascular status, we have investigated the consequences of peroperative myocardial ischemia upon this hemodynamic response. 19 dogs equipped with an electromagnetic flow probe positioned around the ascending aorta served as control (group I). 16 dogs were equipped similarly and in addition submitted to 1 h of myocardial ischemia combined with topical cardiac hypothermia (group II). Hemodynamic studies were carried out 3 h postoperatively and then daily for 1 month, before and during rapid intravenous administration of citrate. From baseline hemodynamic data, cardiac failure was only evident 3 h postoperatively in group II. Transient hypotension and myocardial depression resulted from administration of citrate in both groups with no evidence of peripheral vasodilation. Hypotension and the negative inotropic response were more pronounced in the presence of cardiac failure following peroperative myocardial ischemia. Long-term studies indicate that global myocardial ischemia did not interfere with the cardiovascular adaptability to this pharmacologic interference. PMID- 4043155 TI - Prevention of edema formation in the perfused lung preparation by oxygen radical scavengers. AB - Oxygen-derived free radicals have been implicated as mediators of pulmonary microvascular injury. In the present study we addressed the question of the role of radicals formed in the lung parenchyma in development of pulmonary edema. Rat lungs were perfused with cell-free solutions with and without addition of colloid. Edema formation was measured as dry-wet weight ratios. Edema developed following 30 min perfusion with all perfusates except nonoxygenated Dextran Tyrode. Addition of free radical scavengers, superoxide dismutase and catalase, reduced the edema formation with the various oxygenated perfusates. We conclude that in the isolated lung perfused with oxygenated solutions oxygen-derived radicals are formed that mediate increased permeability. PMID- 4043156 TI - Increased bleeding during liver resection after sympathetic block in normal rats. AB - The effect of sympathetic block on hemostasis after standardized liver resection was studied in the rat. Sympathetic block was undertaken by paravertebral block or surgical sympathectomy. Blood loss was significantly increased, but the bleeding time was not prolonged after paravertebral block. Surgical sympathectomy also increased blood loss as compared to controls, but there was no difference when compared with sham operation. Adenosine diphosphate and collagen induced platelet aggregation was not inhibited in all animals as compared to controls. The results indicate that primary hemostasis was not seriously affected, but that hepatic blood flow was augmented after sympathetic block. PMID- 4043157 TI - Circulatory and renal effects of triglycyl-lysine-vasopressin and excision in experimental burns. AB - The circulatory and renal effects of a deep dermal burn, covering one third of the total body surface area were studied in 12 thiopentone/N2O anesthetized piglets. Central circulation and renal function was monitored during 24 h and regional blood flows were determined before burn, 5 and 24 h after burn using radioactively labeled microspheres. One group was treated conservatively with fluid infusion only (control group) and the other with fluids, intermittent injections of a long-acting hormonogen, triglycyl-lysine-vasopressin (TGLVP), and excision 5 h after burn. There was earlier circulatory recovery in the TGLVP excision group with significantly higher arterial blood pressure and cardiac output than in the controls. TGLVP induced a major redistribution of blood flows, favoring the liver at the expense of the gastrointestinal tract, carcass and skin, while the blood flows were unchanged to the brain, heart and kidneys. There were also increased excretions of sodium and potassium and a temporarily increased diuresis. The earlier circulatory stabilization and blood flow redistribution might have clinical implications in burn care. PMID- 4043158 TI - Urokinase does not prevent abdominal adhesion formation in rats. AB - Damage to the fibrinolytic system preventing the resolution of temporary fibrinous adhesions was repeatedly mentioned as an etiological factor in the process of adhesion formation. We experimentally induced abdominal adhesions in rats by gentle scraping of the entire small bowel. Severe adhesions, sometimes accompanied by intestinal obstruction, developed in all of the control animals. Urokinase, a commonly used and potent fibrinolytic agent and a known plasminogen activator, was administered intragastrically, intraperitoneally, or intravenously at various doses ranging from 5,000 to 100,000 U/kg. Urokinase had no effect on the prevention of abdominal adhesions, nor did it reduce the severity or frequency of adhesion formation. PMID- 4043159 TI - Intra-arterial chemotherapy of infiltrative bladder carcinoma. AB - Twenty patients with untreated invasive high stage or high grade transitional cell carcinoma of the bladder have been treated by bilateral intra-arterial hypogastric injection of adriamycin. A total of 160 mg of adriamycin were injected during the procedure which was repeated once 3-4 weeks later. Eleven patients received two full courses of chemotherapy. In 4 patients, complete response with disappearance of all tumoral lesions was observed and in 1 patient, partial tumor regression was apparent. One patient died from pulmonary disease. Five patients received only a partial treatment because of technical difficulties, and selective catheterization was impossible in 4 because of severe arteriosclerotic lesions. No response was seen in those cases. Although this new therapeutic modality remains to be fully evaluated, preliminary results appear most encouraging since intra-arterial chemotherapy can be used safely and is effective in patients with invasive bladder carcinoma. PMID- 4043160 TI - Anatomical study of total cystoprostatectomy. AB - The authors describe an anatomical study of total cystoprostatectomy. They show that Denonvilliers' fascia is made up of many membranous layers starting at the bladder. They recall the fact that the preprostatic veins are attached at the bottom, not only to the venae dorsales penis, but also to the venae pudendae internae which runs under the levator ani muscle. These preprostatic veins lie inside a vessel-bearing blade of tissue made of muscular and collagenous tissue derived from the anterior vesical wall. This anatomical study recalls the fact that the interprostatorectal dissection line is behind Denonvilliers' fascia and that the preprostatic vein dissection line is on the anterior aspect of the membranous urethra. PMID- 4043161 TI - Natural history of renal artery aneurysm elucidated by repeated angiography and pathoanatomical studies. AB - The findings from repeated angiographies in 16 female and 5 male patients with altogether 34 renal artery aneurysms were studied. The mean interval between the first and last angiography was 35 months. Seven patients had multiple aneurysms. Two to four angiographies were performed in each patient. They showed no change in 28 aneurysms and slight or minimal enlargement, thrombosis or calcification in the other 6. The clinical course was uneventful except for severe hypertension in 3 patients. No rupture occurred. Eight patients, of whom 5 had solitary, saccular aneurysms, were operated upon. Pathoanatomically, fibromuscular dysplasia or secondarily changed fibromuscular dysplasia was found in 7 of them. Four died of unrelated disease having been followed up for 55-204 months (mean 102 months). Nine were alive and symptomless at the end of follow-up 11-195 months (mean 97 months) after the first angiography. The study supports the view that the risk of rupture of a renal artery aneurysm is very small, and indicates that fibromuscular dysplasia is common even when the angiography shows solitary, saccular aneurysm only. PMID- 4043162 TI - Rupture of renal artery aneurysm. AB - Rupture of a renal artery aneurysm, although rare, has been considered to be the most catastrophic urological injury. Three cases of ruptured and 1 case of impending rupture are reported. A review of the cases of ruptured renal artery aneurysm is presented together with emphasis on improved prognosis of this morbidity. Surgical indications are discussed. PMID- 4043163 TI - Renal pelvis reconstruction with a free peritoneal patch. AB - The authors report on the use of a patch of peritoneum in the reconstruction of the renal pelvis. Four successful cases are reported. This leads to the use of such a technique in the reconstruction of the pelvis whenever repair by simple apposition of the margins is impossible. PMID- 4043164 TI - Association of N-acetyltransferase polymorphism and environmental factors with bladder carcinogenesis. Study in a north German population. AB - The N-acetyltransferase phenotype was determined in 105 German patients with bladder carcinoma and in a control group of 42 healthy subjects. The slow phenotype was significantly more frequent among the patients (61.9% compared to 42.9% in the control group). Potential risk factors like occupational exposure, smoking habits, drug abuse and urological anamnestic predispositions were evaluated in relation to staging and grading of the disease, and acetylator phenotype. PMID- 4043165 TI - Residual stump metastasis from renal cell carcinoma. AB - A rare case of ureteral stump metastasis 8 years after nephrectomy for renal cell carcinoma is reported. Twenty-six such cases are reviewed and the etiology of such lesions is discussed. Nephroureterectomy for renal cell carcinoma may be indicated when the risk of urogenous implantation and/or hematogenous spread is present. PMID- 4043166 TI - Benign genital mesothelioma. Two case reports. AB - 2 cases of mesothelioma in the male genital system are reported: one paratesticular, the other in the tail of the epididymis, followed up for 16 months and 4 years, respectively. Clinical, anatomical and pathological findings are discussed. PMID- 4043167 TI - A new urine bag--'Urobag'. PMID- 4043168 TI - Human tumour pH and its variation. AB - The variation in human tumour pH values is large. The aim of this study was to analyse the reasons for these large variations and to determine whether tumour pH can be predicted on the basis of any easily measured parameter. One hundred and five determinations of tumour pH were performed in various human tumours, using the Philips C 902S tissue pH electrode. No correlations were found between the tumour pH and the tumour histology, degree of differentiation, tumour size, patient age or treatment history, and whether or not the tumour was ulcerated. However, tumour pH was significantly lower in primary tumours than in lymph node metastases. Tumours at their primary site (primary, recurrent or residual) were also more acid than distant metastases. The vascular disruption caused by the measuring technique was found to be acceptable. PMID- 4043169 TI - A pilot study of high-dose domperidone as an antiemetic in patients treated with cisplatin. AB - A dose-finding multicenter study was undertaken to evaluate the antiemetic efficacy of domperidone, an antidopaminergic drug, which has been proposed as a suitable alternative to high-dose metoclopramide in the control of cisplatin induced nausea and vomiting. Forty-five patients were treated with different increasing high doses of domperidone (30, 60, 120 or 150 mg) administered by i.v. infusion over 20 min every 2 hr for a total of four doses for each patient, starting 30 min before chemotherapy. The number of episodes of emesis, the duration of nausea and vomiting and side-effects were recorded. Results do not suggest any specific difference in protective effect between the regimens tested. Moreover, occurrence of serious side-effects indicated that the safety of high dose domperidone is doubtful. PMID- 4043170 TI - cis-Platinum and vindesine in combination in the treatment of non-small cell lung cancer. AB - Sixty-three patients with advanced non-small cell carcinoma of the bronchus were treated with a combination of cis-platinum and vindesine. All patients had measurable disease and were of good performance status; none had received prior chemotherapy or radiotherapy. Thirty-three per cent of patients responded, with five patients achieving complete remission. Median duration of response was 4 months, with a median survival of 14 months in the responsers, compared with 6.5 months in the whole group and 4.8 months in the nonresponders. Severe toxicity was encountered, with alopecia, gastrointestinal toxicity and neurotoxicity common. Myelosuppression and renal toxicity were not dose-limiting. Thus the activity of this drug combination is confirmed, but severe toxicity precludes its widespread use in clinical practice. PMID- 4043171 TI - Characterization of the T61 human breast carcinoma established in nude mice. AB - This paper gives a biological characterization of the T61 human breast carcinoma established in nude mice. The human origin of the tumour was verified by the demonstration of the presence of human chromosomes exclusively in the tumour cells. The tumour cells were found by chromosome analysis and flow cytometric DNA analysis to be aneuploid. By electron microscopy, the tumour cells were shown to display the characteristics of glandular epithelium; a light microscopic examination revealed morphological characteristics similar to those of an axillary metastasis of the patient from whom the T61 tumour was derived. Furthermore, the tumour was shown to contain classical receptors for oestrogen and progesterone. The growth of the tumour was characterized by gompertzian growth curves. Since the T61 tumour has a response pattern to endocrine treatment which differs from that described for other human breast tumours grown in nude mice, this tumour may provide a valuable supplement in the study of human breast cancer and endocrine treatment. PMID- 4043172 TI - Misonidazole toxicity and pharmacokinetics in mice: dependence on strain and size. AB - The toxic side-effects of misonidazole (MISO) have been studied in two strains of mice over a wide weight range. The sensitivity of the mice, determined as the LD50 within 7 days of administration, varied by almost a factor of two. Differences were seen in the same strain, with heavy mice being most sensitive, and from strain to strain, with CBA mice being more susceptible than WHT albino mice. The toxicity of the MISO was closely related to a change in the peak blood levels, but showed no correlation with biological half-life. The tissue volume available for drug distribution appears to be reduced in large, heavy mice at high drug doses, and cannot be explained simply on the basis of drug exclusion from adipose tissue. For radiobiological studies with MISO doses of more than 0.5 mg/g it is recommended that it should be administered in a dosage that will give a known blood level of the drug, rather than simply by giving a constant dose based on body weight. PMID- 4043173 TI - Activity of titanocene dihalides against a human colon carcinoma heterotransplanted to athymic mice. AB - The antitumor activity of cis-diamminedichloroplatinum (II) and of two metallocene derivatives, titanocene dichloride (C5H5)2TiCl2 and titanocene dibromide (C5H5)2TiBr2, was investigated against a human colon adenocarcinoma heterotransplanted to athymic mice. The substances were administered at various doses on a Q2DX5 or a Q3DX5 schedule. Whereas cis-diamminedichloroplatinum (II) induced an only marginal tumor-inhibiting effect, both titanocenes markedly suppressed tumor development (T/C values: 23-40%) and caused stagnation and relative decrease of tumor growth, when they were applied in subtoxic doses far below the LD10 level. The results are remarkable with respect to the general insensitivity of human colorectal carcinomas to cytostatic agents. PMID- 4043174 TI - Rat liver-mediated degradation of dibromodulcitol. AB - The rate and extent of dibromodulcitol (DBD) conversion by 9000 g rat liver supernatant with an NADPH-generating system (S-9 mix) were studied using 3H labelled drug. Results indicated that S-9 mix seemed to exert an initial protective effect delaying the solvolysis of DBD for about 30 min at 37 degrees C followed by rapid degradation into exclusively pharmacologically inactive products. Thus S-9 mix contained merely DBD as an effective agent; it amounted to less than 40% of the total radioactive compounds by 120 min. In the control mixtures the sovolytically produced effective drug content, i.e. the sum of DBD, 1,2-anhydro-6-bromo-6-deoxygalactitol (BrEpG), 1,2-5,6-dianhydrogalactitol (DAG) was 63%. Our results suggest the involvement of liver enzymes in the detoxification of DBD into inactive products. Therefore the antitumour effect of DBD cannot be attributed to its active BrEpG and DAG alone. The drug in its unchanged form may contribute to a somewhat greater extent to its cytostatic action than was believed before. PMID- 4043175 TI - Inflammatory tumor response to monoclonal antibody infusion. AB - Two patients with melanoma and one with apudoma, all three with metastatic disease, received monoclonal antibody infusions with mAb R-24, specific for the disialoganglioside GD3. This marker was shown to be restricted to melanoma cells and a few other tumors of neural crest origin. Following treatment with mAb R-24 both melanoma patients showed inflammatory cutaneous responses around tumor nodules, i.e. blister formation or inflammatory perinodular halos. Local pain in bulky intestinal tumor sites occurred in all three patients about 3 hr after onset of antibody infusion. Adverse side-effects of antibody application were not observed with antibody doses up to 200 mg (single) and 440 mg total dose. The presented data indicate that mAb R-24 is active in vivo. PMID- 4043176 TI - Serum sialyltransferase and fucosyltransferase activities in patients with multiple myeloma. AB - A significant elevation of serum sialyltransferase and fucosyltransferase mean activities was observed in 19 untreated patients with multiple myeloma. However, sialyltransferase mean activity was significantly lower in 13 other patients treated for 1-30 months with alkylating drugs and prednisolone. Such a definite decrease in serum enzyme activity on treatment was not recorded for fucosyltransferase. Instead, this activity was significantly increased in treated patients as compared to controls. The presenting clinical features of the 32 patients with multiple myeloma were the basis for a clinical staging system with regard to myeloma cell burden according to established criteria. In untreated patients (as opposed to treated ones), a significantly higher serum sialyltransferase (but not fucosyltransferase) activity was obtained among those 11 belonging to stage III than among the other eight with stages I and II, suggesting a link between tumour burden and enzyme activity. This assumption was further strengthened in those six patients followed lengthwise with regard to serum sialyltransferase activity. Concomitantly with objective evidence of change in tumour burden they showed corresponding alterations in sialyltransferase activity. The determination of sialyltransferase and fucosyltransferase activity in serum may be an additional contribution to refine initial assessment and follow-up of individual patients with multiple myeloma. PMID- 4043177 TI - Relation between enzymatic activities and the degree of malignancy of human lymphomas. AB - The relationship between the intracellular levels of DNA polymerase alpha (DP alpha), adenosine deaminase (ADA) and lactate dehydrogenase (LDH) and the degree of malignancy of human lymphomas was investigated. Twelve non-neoplastic lymph nodes and 88 malignant lymphomas were examined. For non-Hodgkin's lymphomas (NHL) the low or high grade of malignancy was established according to three classifications: the Rappaport, the Kiel and the Working Formulation for Clinical Usage, with the latter also recognizing an intermediate grade group. Non neoplastic lymph nodes had significantly lower levels of all the three enzymes than those found in high-grade malignant NHL (the P value ranged from less than 0.02 to less than 0.001). Hodgkin's disease, a slowly evolving neoplasia, showed lower levels of DP-alpha (P less than 0.001) and ADA (P less than 0.001), but not of LDH, than high-grade NHL. Among NHL, whatever classification was used, the low grade malignant lymphomas had significantly lower levels than the high-grade ones for all the three enzymes (P less than 0.005 or P less than 0.001). The intermediate-grade group of the Working Formulation differed from the high-grade group for DP-alpha (P less than 0.01) and ADA (P less than 0.02) but not for LDH. It differed from the low-grade group only for ADA (P less than 0.005). Lymphoblastic and Burkitt's lymphomas were the groups with the highest levels of the three enzymes. Among low-grade lymphomas very low values were found in the histological entities defined as DLWD in the Rappaport classification, CLL and lymphoplasmacytoid immunocytoma in the Kiel classification and small lymphocytic (group A) in the WF. The levels of all enzymes in these histotypes were always significantly different from the other low-grade histotypes, and from the intermediate-grade ones of the WF. In the Kiel classification polymorphous lymphoplasmacytoid lymphoma, recently recognized as a group with a quite aggressive clinical course, was characterized by high levels of all three enzymes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4043178 TI - Sympathetic ganglia augment growth of neuroblastoma in vitro. AB - The sympathetic nervous system modulates the growth of C-1300 mouse neuroblastoma (C-1300 NB) in vivo. We now report that the presence of sympathetic cervical ganglia in cultures containing C-1300 NB or dispersed S-20 neuroblastoma (S-20 NB) cells augments growth of these tumors in vitro. Sympathetic ganglia conditioned medium increases proliferation and survival of S-20 NB cells, indicating that nervous system-derived growth factors can exert an effect on neoplastic cells. PMID- 4043179 TI - Assay for estrogen and progesterone receptors of breast cancer cell lines in monolayer culture. AB - A whole-cell assay for measuring estrogen (ER) and progesterone (PgR) receptors in monolayer culture of human breast cancer cell lines is described. It is based on the measurement of incorporated tritiated ligands during 50 min of incubation (i.e. [3H]estradiol for ER, [3H]ORG-2058 for PgR). The assay fulfills all criteria of specificity as shown by competitive studies and measurements of the dissociation constants of the binding reactions. Moreover, a subcellular fractionation of MCF-7 labeled cells revealed that the majority of incorporated steroids was associated with the nuclear fraction. This finding is consistent with the concept of nuclear location of steroid-receptor complexes. Cultures in the presence of 10(-8) M estradiol indicated that the methodology is adequate for detecting the well-known estrogenic induction of PgR synthesis. The assay proved suitable for the quantitative assessment of the receptor content of various neoplastic (MCF-7; ZR-75-1, Cama-1, Evsa-T) and non-neoplastic (HBL-100) cell lines. The methodology has the other advantages of being simple and rapid, of requiring small amounts of cells and of allowing histological examination of the latter before, during and after biochemical analysis. PMID- 4043180 TI - The effect of treatment with single and split doses of spirohydantoin mustard on the growth delay of 9L rat brain tumor multicellular spheroids. AB - The effects of single and split doses of spirohydantoin mustard on the growth delay and cell survival of 9L rat brain tumor multicellular spheroids have been investigated. Treatment with 10-25 microM concentrations of spirohydantoin mustard inhibited the growth of spheroids. Growth delay increased rapidly when assayed during the first 6-10 days after treatment, after which a decrease in delay was observed. Plots of the values for the inflection points from growth curves vs drug concentration were linear, and growth delay correlated well with cell survival. There was less growth delay caused by treating spheroids with two 10 microM concentrations of spirohydantoin mustard than with a single 20 microM concentration. When a 2 or 4 hr time interval was allowed between treatment with 10 microM concentrations of spirohydantoin mustard the delay observed was greater than that obtained with the split dose control. When the resolution of the growth delay assay is considered, the split dose effect can be explained by the existence of a 5 microM threshold before any growth delay is observed. Nonetheless, the finding that spheroids treated on the split dose protocol recover from drug damage may have implications for the design of clinical protocols. PMID- 4043181 TI - In vivo and in vitro antiestrogenic action of 3-hydroxytamoxifen, tamoxifen and 4 hydroxytamoxifen. AB - This study demonstrates in vivo and in vitro properties of the non-steroidal antiestrogens tamoxifen (TAM), 4-OH-tamoxifen (4-OH-TAM) and 3-OH-tamoxifen (K 060 E). In immature rabbit uteri 4-OH-TAM and K 060 E bound to the respective estrogen receptors with a ten-fold higher affinity than TAM. Furthermore, K 060 E exhibited less agonistic (estrogenic) but higher antagonistic (antiestrogenic) activity in the immature rat uterus than TAM and 4-OH-TAM (change of uterine weight). The ratio of agonistic vs antagonistic effect of K 060 E was distinctly lower than in TAM and 4-OH-TAM. In addition, K 060 E reduced by approximately 45% the growth of the transplantable Fisher rat mammary tumor (R 3230 AC) as compared with TAM (33%). We assume that, due to the higher antitumor activity, K 060 E (3 OH-TAM) is a better antiestrogen than TAM. PMID- 4043182 TI - Differential effect of i.p.- and i.v.-injected adriamycin on the clonogenic spermatogonia of murine testis. AB - The response of murine clonogenic spermatogonia has been measured after intraperitoneal or intravenous injections of adriamycin (ADR). When measured over the whole testis, the survival curve for regenerating tubules after i.p. ADR had a 10-15% lower LD37 dose (that dose which sterilises 37% of tubules) but a two fold higher average D0 for the clonogenic cells than that for i.v. ADR. Survival was then measured in concentric zones of these equatorial sections of testis. For i.v. injection survival parameters varied little between zones in the centre of the testis and zones adjoining the testicular capsule. In contrast, for i.p. ADR central zones had a 40% higher LD37 but the same D0 as for i.v. ADR, while peripheral zones had LD37s as little as 35% of the i.v. figure and mean D0s 2-3 times higher. Pharmacokinetic considerations that might lead to these differences in clonogenic response are discussed. PMID- 4043183 TI - Spelling instruction in special education classrooms: a survey of practices. PMID- 4043184 TI - From school to work: a vocational transition model for handicapped students. PMID- 4043185 TI - Hearing impaired students in regular classrooms: a cognitive model for educational services. PMID- 4043186 TI - Large-scale learning disability identification: the reprieve of a concept. PMID- 4043187 TI - Variations in attention as a function of classroom task demands in learning handicapped and CA-matched nonhandicapped children. PMID- 4043188 TI - Importance of goal ambitiousness and goal mastery to student achievement. PMID- 4043189 TI - Low achiever differentiation: where's the beef? PMID- 4043190 TI - The effects of cooperative and individual goal structures on learning disabled and nondisabled students. PMID- 4043191 TI - Postsecondary vocational adjustment of rural, mildly handicapped students. PMID- 4043192 TI - Teachers' perceptions of behaviorally disordered students in a variety of settings. PMID- 4043193 TI - California's new eligibility criteria: legal and program implications. PMID- 4043194 TI - Facilitating mainstreaming by modifying the mainstream. PMID- 4043195 TI - The effects of integration on the mathematics achievement of hearing impaired adolescents. PMID- 4043196 TI - Biasing influences on test level assignments for hearing impaired students. PMID- 4043197 TI - Effects of role, gender, age, and parental status on perception of childhood problems. PMID- 4043198 TI - Overestimation of renal function in glucocorticosteroid treated patients. AB - Creatinine clearance is commonly used as a parameter for individualization of dosages of drugs primarily excreted by the kidney. Nomograms and equations have been developed for estimating creatinine clearance from serum creatinine concentration, body weight, age and sex. Glucocorticosteroids are said to cause proximal muscle wasting and therefore may be expected to cause a decrease in the creatinine production rate. The purposes of the present investigation were first to evaluate by a computed tomography the effect of long term treatment with prednisone on the mid-thigh muscle area, and second, to establish whether the presumed supposed decrease in muscle mass was associated with a decrease in the urinary creatinine excretion rate, and hence in a systematic error whenever a nomogram is used to predict creatinine clearance in such subjects. Patients taking prednisone had smaller mid-thigh muscle areas than controls. A linear relationship between the mid-thigh muscle area and the observed urinary excretion of creatinine was found, suggesting that the muscle loss could account for the decrease in the urinary excretion rate of creatinine. The ratio of observed to predicted (by nomogram) urinary creatinine excretion was lower in patients than controls, resulting in a corresponding underprediction of creatinine clearance by nomograms in the patients taking prednisone. PMID- 4043199 TI - Evaluation of infusion regimens for thiopentone as a primary anaesthetic agent. AB - Several multi-stage infusion regimens and a computer controlled exponentially decreasing infusion regimen were evaluated in twelve patients undergoing head and neck surgery or neurosurgery. Thiopentone dosage was based on the mean of pharmacokinetic parameter values from the literature and adjusted for each patient's lean body mass in order to rapidly achieve a predetermined plasma thiopentone concentration of 15 or 20 micrograms/ml in the period following the initial bolus dose to induce anaesthesia. Anaesthesia was satisfactory in all cases. Plasma thiopentone concentrations were maintained between 10-20 micrograms/ml during infusion in the five patients who received either a four or five stage infusion and in the six patients who received the exponential infusion, but not in the single patient who received a two-stage infusion. The mean recovery time was 111 min. The plasma concentrations of total and unbound thiopentone at awakening showed little intersubject variability, despite considerable differences in total dose and duration of infusion, suggesting the absence of acute tolerance to the drug. Plasma clearance of total thiopentone correlated strongly with calculated lean body mass and to a lesser extent with total body weight suggesting that lean body mass, in particular, should be an accurate predictor of thiopentone maintenance dose requirements. This study shows that it is feasible to use thiopentone as a primary anaesthetic agent during surgery by administering the drug either as an exponentially decreasing infusion or as an infusion comprising 4 or 5 stepwise decreasing rates. PMID- 4043200 TI - The influence of ascites on the pharmacokinetics of piretanide in cirrhotic patients. AB - The pharmacokinetics of piretanide, a new loop diuretic, were studied in seven patients with severe liver disease before and after resolution of ascites. The time to maximum concentration was significantly prolonged by the presence of ascites. Tmax after relief of ascites was similar to that seen for normal volunteers. Area under the curves, bioavailability, volumes of distribution and elimination half-lives did not change after resolution of the ascites: two patients in whom diuretic resistant ascites occurred showed similar pharmacokinetics to that of the diuretic responders. Reduced responsiveness to piretanide therapy in patients with gross ascites does not appear to be the result of decreased bioavailability. PMID- 4043201 TI - Effect of impairment of renal function on the accumulation and disposition of isoxicam. AB - The accumulation and disposition of the non-steroidal antiinflammatory drug isoxicam were investigated following its oral administration to 6 subjects with normal renal function and 13 patients with diminished renal function. Isoxicam was given daily as a single oral dose for 14-15 consecutive days. Steady-state plasma levels were achieved after 13 days. The effect of differences in renal function on the kinetics of isoxicam appeared to be minimal. Accumulation of isoxicam was similar in both groups of subjects and there was no significant difference between the groups in the plasma clearance or terminal half-life of isoxicam. There were substantial differences between individuals in the apparent plasma clearance and half-life of the drug, and this is reflected in the 7-fold range of steady-state plasma isoxicam concentrations encountered in the subjects. PMID- 4043202 TI - Antipyrine metabolite formation and excretion in patients with chronic renal failure. AB - In the present study the influence of chronic renal insufficiency on antipyrine clearance, metabolite formation and excretion was investigated in 8 patients. After oral administration of antipyrine, the parent compound, its metabolites and their conjugates were assayed in plasma and urine. Besides the parent drug, 3 hydroxymethylantipyrine (HMA) was present in plasma in the free and conjugated forms, whereas 4-hydroxyantipyrine (OHA) and norantipyrine (NORA) were found only in the conjugated form. The same was true for urine. The plasma concentrations of these metabolites are too low to be measured in subjects with normal renal function. Plasma antipyrine clearance in the patients was in the same range as in healthy subjects. Investigation of metabolite kinetics, however, revealed that the rate of formation of NORA was preferentially decreased, whereas that of OHA and HMA were unaltered. Renal clearance of the metabolites of antipyrine was severely impaired in patients with renal insufficiency, and the resulting accumulation made it possible for the first-time to measure the antipyrine metabolites in plasma. Mean residence times of metabolites were longer than that of the parent compound. Renal clearances of the conjugates were correlated with the creatinine clearance, but were somewhat higher. Renal clearance of free HMA was lower and was also correlated with creatinine clearance. The mean clearance for glucuronidation of HMA was 93.1 ml/min. The results suggest that in healthy subjects Phase I metabolism is the rate-limiting step in the elimination of antipyrine, which is essential for its application as a model drug in metabolism studies. PMID- 4043203 TI - Transfer of labetalol into amniotic fluid and breast milk in lactating women. AB - The transfer of labetalol into human breast milk and amniotic fluid was studied in women with pregnancy hypertension. The women were treated with labetalol 600 1200 mg daily. The ratio between the areas under the milk and plasma concentration versus time curves varied between 0.8 and 2.6. No consistent relation between milk and plasma concentration in the mother was observed either within the individuals during a dose interval or between different individuals. One of the nursed infants at the end of the dose interval had a plasma labetalol in the same range as the mother, and in another infant the level was below the detection limit. Amniotic fluid concentrations 2-3 h after dosing were generally lower than in plasma. PMID- 4043204 TI - Hepatobiliary transport of plasma IgA in the mouse: contribution to clearance of intravascular IgA. AB - Labeled monomeric and polymeric (pIgA) mouse monoclonal IgA were injected intravenously into mice which were either sequentially bled for plasma turnover studies of IgA, or cannulated at their common bile duct, with excluded gallbladder, for quantitation of plasma-to-bile transport of pIgA. Our data show that mice do display a relatively high rate of biliary transport of plasma pIgA (22-28% of the injected 125I-labeled pIgA over 3 h), which accounts for approximately 90% of the total amount of pIgA (8.8 mg/kg/day) daily delivered by hepatic bile into the duodenal fluid of this species. However, in mice the absolute biliary output of pIgA does not exceed that of IgG (9.5 mg/kg/day) and the kinetics of the hepatobiliary transport of plasma pIgA appear to be slower than in the rat. Furthermore, as plasma survival studies of 125I-labeled pIgA yielded a plasma turnover of pIgA averaging 20.6 mg/kg/day, it can be approximated that the hepatobiliary pathway contributes for only 38% to the elimination of intravascular pIgA from mouse plasma, a figure to be compared to 89.8% in the rat and approximately 8.9% in man. We conclude that internal catabolism plays a dominant role in the clearance of intravascular pIgA in the mouse which appears as a model intermediate between rats and humans. Supporting this conclusion, serum pIgA two days after common bile duct ligation in 6 mice was increased by 2.5-fold vs. greater than 14-fold in ligated rats and 1.1-fold in humans with complete biliary obstruction. PMID- 4043205 TI - Ultrastructure of human C4-binding protein: proposition for a new model. AB - The structure of human C4-binding protein (C4bp), a regulatory factor of the classical C3 convertase of complement, has been under investigation for several years, but remains poorly understood. For example, the number of subunits in the C4bp molecule has not been established. In this report, we use two different techniques (partial reduction and electron microscopy) to clarify the structure of the C4bp. Our results lead us to propose a structural model which is quite different to that suggested before, i.e. the C4bp molecule appears to be a decamer. In addition to the disulfide bonds which link each subunit to another, a second disulfide interaction leads to the association of the subunits in pairs. Each pair of subunits appears as a filament ending in a globular head at the N terminal extremity. The pairs of subunits join to form a conical central domain (at the C-terminal extremity) linked by disulfide bonds. The proposed pentameric shape of the C4bp is consistent with the stoichiometry of the C4b-C4bp interactions. The proposed model indicates an overall structural homology between C4bp and other binding proteins. PMID- 4043206 TI - Demonstration of specific binding sites for [3H]mazindol in rat hypothalamus: correlation with the anorectic properties of phenylethylamines. PMID- 4043207 TI - Adenosine inhibits forskolin-induced excitation in myenteric neurons. PMID- 4043208 TI - Prazosin but not rauwolscine reduces a component of the constrictor action of thrombin in the rabbit femoral artery. PMID- 4043209 TI - Autoradiographic localization of [3H]methylphenidate binding sites in rat brain. PMID- 4043210 TI - Possible mechanism of action of diazepam as an adenosine potentiator. AB - Diazepam (10(-5)-3 X 10(-4) M) selectively enhanced the negative inotropic responses of guinea-pig atria and the relaxation of guinea-pig taenia coli caused by adenosine and ATP. In the atria, the effect of 2-chloroadenosine, a stable analog of adenosine, was not affected by diazepam. Segments of guinea-pig atria or taenia coli took up 3H-activity during incubation with [3H]adenosine but did not take up 32P-activity from [32P]ATP. Diazepam at concentrations sufficient to enhance the in vitro responses reduced by half the uptake of 3H-activity into the preparations. Adenosine (10(-6) M) and ATP (10(-6) M) were degraded to inactive inosine during incubation with atrial segments and their degradation was inhibited by diazepam. In contrast, in rat atria, diazepam did not enhance the negative inotropic effects of adenosine and ATP, and did not prevent the uptake of adenosine. These results suggest that in guinea-pig atria and taenia coli, diazepam like dipyridamole, acts as an adenosine potentiator by preventing the uptake and degradation of adenosine. PMID- 4043211 TI - Systemic and regional hemodynamic actions of calcium entry blockers in conscious spontaneously hypertensive rats. AB - In the present study we investigated systemic and regional hemodynamic effects of the calcium entry blockers nifedipine, verapamil and PY 108-068 in conscious SHR. For systemic hemodynamic studies the animals were instrumented with an electromagnetic flowprobe on the ascending aorta, whereas for regional hemodynamic studies miniaturized Doppler flowprobes were implanted on the superior mesenteric and left renal artery and on the abdominal aorta. All three drugs caused a dose-dependent fall in mean arterial pressure and total peripheral resistance. Nifedipine and PY 108-068 increased cardiac output and heart rate, whereas verapamil only did so at high doses. Administration of each calcium entry blocker caused a dose-dependent fall in skeletal muscle vascular resistance, with renal and mesenteric resistance remaining virtually unchanged. A similar effect was observed after the administration of nifedipine to normotensive WKY rats. Surgical elimination of sino-aortic baroreflexes caused a 10 fold increase in antihypertensive potency of the three drugs in SHR. Moreover, dilatation in these animals was uniform in all beds studied. The results indicate that the three calcium entry blockers used are essentially non-selective vasodilators but that baroreflex mechanisms prevent vasodilatation in the renal and mesenteric beds in intact animals. PMID- 4043212 TI - Psychopharmacological effects of nomifensine enantiomers. AB - The effects of enantiomers of nomifensine were compared in five psychopharmacological tests in which (+/-)-nomifensine is active. In mice, (+) nomifensine increased motor activity at 16 mg/kg, 8 mg/kg reduced the hypothermia and ptosis induced by reserpine and antagonized the hypothermia induced by 16 mg/kg of apomorphine. (+)-Nomifensine 4 mg/kg potentiated yohimbine toxicity. (-) Nomifensine 4,8, or 16 mg/kg was inactive in all these tests. In rats, (+) nomifensine 8 mg/kg induced stereotyped movements whereas (-)-nomifensine 64 mg/kg did not produce stereotypies. PMID- 4043213 TI - Acute effects of taurine and a taurine antagonist on ethanol-induced central nervous system depression. AB - Sprague-Dawley rats received taurine intracerebroventricularly (i.c.v.) 30 min prior to ethanol (4 g/kg, i.p.). The duration of ethanol-induced sleep time was increased with taurine at doses of 7.5, 14.0 and 25.0 mumol/kg. In another experiment, TAG (a taurine antagonist, i.c.v.) was given 5 min prior to taurine (i.c.v.) and ethanol was administered 30 min later. TAG antagonized the effect of taurine to enhance ethanol-induced sleep time. These results suggest an interaction between taurine and the depressant effect of ethanol in the brain. PMID- 4043214 TI - Role of prostaglandins and the areas postrema in the central pressor action of bradykinin. AB - Vertebral and carotid artery infusions of bradykinin increased blood pressure and heart rate in anaesthetised greyhounds. Indomethacin pretreatment abolished the pressor response to vertebral infusion and reduced that to carotid infusion. Areas postrema ablation abolished the pressor response to bradykinin with both routes of administration. The tachycardia responses to cranial artery infusions and the entire cardiovascular response to intravenous infusion were unaffected by either treatment. It is concluded that intact areas postrema and normal prostaglandin synthesis are essential for the full expression of the central pressor action of bradykinin. PMID- 4043215 TI - Effects of adenosine on 45Ca uptake and [3H]acetylcholine release in synaptosomal preparation from guinea-pig ileum myenteric plexus. AB - The effects of adenosine on acetylcholine (ACh) release and calcium uptake were examined in a synaptosomal fraction prepared from guinea-pig ileum myenteric plexus-longitudinal muscle. A high concentration of potassium (40 mM) and electrical pulses (ES:10Hz) caused a marked increase in the output of [3H]ACh from [3H]choline-preloaded crude synaptosomes. This [3H]ACh output was calcium- and temperature-dependent. Adenosine reduced the high potassium-induced release significantly, and the electrically stimulated release completely. When the preparation was depolarized by high potassium or electrical pulses, the 45Ca uptake by synaptosomes was significantly enhanced. The uptake of 45Ca induced by high potassium was significantly reduced and that induced by electrical stimulation was completely abolished by adenosine. From these results, it may be suggested that adenosine inhibits neurotransmitter release by suppressing the presynaptic influx of calcium ion during depolarization of the cholinergic nerve terminals in guinea-pig ileum. PMID- 4043216 TI - Profile of prostaglandins generated in the detrusor muscle of rat urinary bladder: effects of adenosine triphosphate and adenosine. AB - The generation and release of PGE2, PGF2 alpha, PGD2, TXB2 and 6-keto-PGF1 alpha in the rat detrusor muscle were studied by means of radioimmunoassays. The effect of ATP (0.1 mmol/1) and adenosine (0.1 mmol/1) on the content and profile of PGs in the incubation medium was investigated. It was found that PGE2 and 6-keto-PGF1 alpha accounted for more than 80% of the total PG activity. ATP increased the amounts of PGs in the incubation medium (percentage change of the control values, N = 6: PGE2 54.53 +/- 12.69, PGF2 alpha 31.01 +/- 8.82, PGD2 44.52 +/- 12.36, TXB2 17.29 +/- 10.45, 6-keto-PGF1 alpha 36.62 +/- 5.0) but did not change their profile. Adenosine had no effect on either content or profile of the PGs. The results suggest that ATP but ot adenosine may activate PG biosynthesis via P2 purinoceptor-mediated mechanisms. PMID- 4043217 TI - Capsaicin pretreatment inhibits the flare component of the cutaneous allergic reaction in man. PMID- 4043218 TI - Effects of catecholamines, monophenolamines and phenylamines on identifiable giant neurons of an African giant snail (Achatina fulica Ferussac). AB - The effects of catecholamines, monophenolamines and phenylamines on eight identifiable giant neurons of an African giant snail (Achatina fulica Ferussac) were examined to classify these neurons into several categories according to their sensitivities to the various substances. The five neurons, PON (periodically oscillating neuron), TAN (tonically autoactive neuron), 1-VMN (left visceral multiple spike neuron), d-RPeAN (dorsal-right pedal autoactive neuron) and VIN (visceral intermittent firing neuron), were sensitive to catecholamines. Of these neurons, PON was excited most markedly by dopamine (dopamine-sensitive); TAN, 1-VMN and d-RPeAN were inhibited most markedly by epinine (epinine sensitive); and VIN was excited equally by the four catecholamines, dopamine, epinine, L-noradrenaline and L-adrenaline (widely sensitive). The three other neurons, FAN (frequently autoactive neuron), d-LPeLN (dorsal-left pedal large neuron) and d-LCDN (dorsal-left cerebral distinct neuron) were sensitive to monophenolamines. DL-Octopamine was the most inhibitory on FAN and d-LCDN, but was the most excitatory on d-LPeLN. DL-Synephrine had the same but somewhat weaker effects on the three neurons as did DL-octopamine. The three phenylamines, L-phenylalanine, beta-phenylethylamine and DL-beta-phenylethanolamine, had no effect on any of the eight neurons examined. PMID- 4043219 TI - Characterization of a high affinity piretanide receptor on kidney membranes. AB - The tritiated loop diuretic, piretanide, is a useful ligand for specific diuretic receptors which are present in the plasma membranes of renal medullary cells. Its high specific activity (30 Ci X mmol-1) made it possible to demonstrate the existence of a high affinity receptor (Kd approximately 5 nM) and a binding site with low affinity. High affinity binding is saturable, reversible and displaceable by a number of non-radioactive loop diuretics. Structural analogues, devoid of diuretic activity, do not displace piretanide binding. No specific binding occurs in liver or spleen membranes. PMID- 4043220 TI - Contractile responses of the guinea-pig esophageal muscularis mucosae in vitro to arachidonic acid and its metabolites. AB - The responsiveness of the guinea-pig esophageal muscularis mucosae to arachidonic acid (AA) and its cyclooxygenase and lipoxygenase metabolites was examined in vitro. AA (0.1-30 microM) produced a concentration-dependent contraction of the muscularis mucosae (mean EC50 +/- S.E.M. = 5.1 +/- 1.0 microM). The contractions in response to low concentrations of AA (0.1-3 microM) were prevented by pretreatment of the tissue with indomethacin (1-10 microM), while those in response to high concentrations (10-100 micron) were prevented by BW755C (10-100 microM). The contractile response to AA was antagonized by polyphloretin phosphate (PPP, 1-10 micrograms/ml) and by FPL 55712 (1-10 microM). All cyclooxygenase and lipoxygenase metabolites of AA tested also produced a sustained contraction of the muscularis mucosae with the following order of sensitivity; leukotriene (LT) D4 greater than LTC4 greater than prostaglandin (PG) E2 greater than PGF2 alpha greater than PGI2 greater than thromboxane B2. The responses to LTC4 and LTD4 were antagonized by FPL 55712 (0.1-1 microM), while those to PGE2 and PGF2 alpha were antagonized by PPP (3-100 micrograms/ml). The present results indicate that exogenously applied AA contracts the isolated muscularis mucosae of the guinea-pig esophagus by an indirect action via its metabolism to both PGs and LTs. The putative PG and LT receptors located in this tissue are probably similar to those in the ileal longitudinal muscle, but differ from those in the airway smooth muscle. PMID- 4043221 TI - Central opioid-like influence of a tetrapeptide from hamster embryo (kentsin) on gastrointestinal motility in dogs. AB - The effects of intracerebroventricular (i.c.v.) vs. intravenous (i.v.) administration of kentsin (H-Thr-Pro-Arg-Lys-OH) on gastrointestinal motility were investigated in fasted dogs. Administered i.c.v. at doses of 20 and 100 ng/kg, this peptide inhibited by 51.2 and 76.1% the antral motility index and disrupted the jejunal migrating motor complex for 2 and 4 h respectively. Similar effects were only obtained after a 25 fold higher dose administered i.v. and these effects were abolished after a previous i.c.v. administration of naloxone (50 micrograms/kg) suggesting that they are mediated through opiate receptors. PMID- 4043222 TI - Effect of alpha-chymotrypsin on the nonadrenergic noncholinergic inhibitory system in cat airways. AB - Electrical field stimulation of 5-hydroxytryptamine contracted cat trachea and bronchi in the presence of cholinergic and adrenergic blockade caused relaxation by activating intrinsic nonadrenergic noncholinergic (NANC) inhibitory nerves. Pretreatment of the tissues with the proteolytic enzyme, alpha-chymotrypsin, did not affect NANC inhibitory responses. Relaxations induced by vasoactive intestinal peptide (VIP) were abolished by alpha-chymotrypsin. These results suggest that VIP or related peptides may not act as the NANC inhibitory transmitter in cat airways. However, the possibility remains that peptides not susceptible to degradation by alpha-chymotrypsin may mediate these NANC inhibitory responses. PMID- 4043223 TI - Endothelium removal augments vasodilation by sodium nitroprusside and sodium nitrite. AB - Sodium nitroprusside (3-100 nM) and sodium nitrite (0.03-1 mM) caused relaxation of the rat aortic ring segments precontracted by norepinephrine. The relaxation was significantly augmented by removal of endothelium, and this augmentation was greater in the aorta from spontaneously hypertensive rats (SHR) than Wistar Kyoto rats (WKY). The mechanism remains unknown but such augmentation may be clinically favorable to the use of nitrovasodilators. PMID- 4043224 TI - Bombesin stimulates small intestinal motility after intracerebroventricular administration to rats. AB - The frequency and amplitude of contractions occurring in the duodenum and the jejunum of freely-moving, unanesthetized, female Sprague-Dawley rats were determined by continuously recording intestinal intraluminal pressure. Intracerebroventricular (i.c.v.) administration of saline did not significantly alter the frequency of contractions in either small bowel region when compared with activity observed during a preinjection control period. I.c.v. administration of bombesin (0.1-10 micrograms) produced a dose-related increase in the frequency of duodenal contractions of up to 583% of control. While an increase in jejunal motility was consistently seen with doses of 1 and 10 micrograms, the lowest bombesin dose tested (0.1 microgram) produced a significant decrease in the frequency of contractions in this intestinal area. The intestinal motor effects were seen within the first 30 min after the peptide, and lasted for at least 1 h. Intraperitoneal administration of bombesin, at doses 200 times higher than those given centrally, failed to significantly alter intestinal motility at either recording site. Whether all of the complex intestinal motor effects of bombesin can be directly related to its centrally initiated inhibitory transit effect is unclear; however, the stimulation of contraction frequency in the duodenum at all doses tested suggest that the antitransit effects of bombesin may be, in part, the result of either an increase in the frequency of non-propulsive contractions or a disruption of the normal coordinated propulsive motility pattern of the duodenum. PMID- 4043225 TI - Cross-tolerance between morphine- and bombesin-induced inhibition of intestinal transit in rats. AB - Intracerebroventricular (i.c.v.) injection of either morphine or bombesin to rats inhibits intestinal transit of an intraduodenally administered radiochromium marker. In this work, we show that tolerance develops to this effect of bombesin after i.c.v. infusion of the peptide (0.5 micrograms/h for 4 days via an s.c. implanted Alzet 2001 osmotic minipump). Tolerance also develops to the inhibition of intestinal transit associated with i.c.v. morphine after s.c. injections of morphine. Bombesin-induced delay of transit is not attenuated by naltrexone (10 mg/kg, s.c.), a standard narcotic antagonist. Nevertheless, two-way cross tolerance develops between bombesin and morphine in this system. This is a surprising result since both bombesin and morphine are believed to act on different receptors and cause opposite effects on intestinal motility in rats. PMID- 4043226 TI - The dynamics of dopamine metabolism in the rat superior cervical, coeliac and mesenteric ganglia. AB - Dopamine (DA) metabolism was compared in rat superior cervical ganglion, coeliac ganglion, mesenteric ganglion and adrenal medulla. Substantial amounts of DA, 3-4 dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) were found in all the above structures. The proportion of DA metabolites over total adrenergic compounds increased from the superior cervical (22 +/- 2.2%) to the mesenteric ganglia (37 +/- 1.4%) and was much higher in ganglia (30 +/- 1.6%) than in adrenal medulla (1.1 +/- 0.3%). The turnover rates of DOPAC and HVA were calculated in sympathetic ganglia after pargyline (75 mg/kg i.p.) or probenecid (200-500 mg/kg i.p.). After pargyline, the DOPAC levels decreased faster than HVA levels in all ganglia. The corresponding half-lives and calculated turnover rates were: about 4 and 10 min and 100 and 40 pmol/mg protein per h for DOPAC and HVA respectively. No differences were observed between the three ganglia. After probenecid, DOPAC accumulated in all the ganglia in a dose-dependent way; HVA accumulated in the superior cervical and coeliac ganglia but not in the mesenteric ganglion. As in central areas, the turnover rates of DOPAC and HVA calculated on the basis of the greatest accumulation of acidic levels after probenecid were much smaller than those obtained after pargyline. Probenecid increased DOPAC levels in adrenal medulla, but the concomitant changes in DA and epinephrine (E) amounts suggest that probenecid was able to enhance adrenomedullary activity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4043227 TI - Involvement of monoaminergic and peptidergic components in cathinone-induced analgesia. AB - Evidence has been obtained suggesting that cathinone-induced analgesia depends upon stimulation of alpha-adrenoceptors, followed by release of opioid peptides and by activation of serotonergic pathways. This hypothesis is supported by the following. (1) Cathinone potentiated morphine analgesia and the whole effect was antagonized by naloxone whereas onto the cathinone potentiation was counteracted by phenoxybenzamine. (2) Bestatin potentiated cathinone-induced analgesia and this effect was sensitive to both naloxone and phenoxybenzamine blockade. (3) The analgesic effect of cathinone + bestatin was further potentiated by the serotonin uptake inhibitor citalopram. PMID- 4043228 TI - Atropine-resistant excitatory junction potentials in rabbit bladder are blocked by alpha,beta-methylene ATP. PMID- 4043229 TI - Bombesin, gastrin releasing peptide and vasoactive intestinal peptide excite myenteric neurons. AB - Intracellular recording methods were used to study the actions of bombesin, gastrin releasing peptide and vasoactive intestinal peptide on electrical behavior of AH/Type 2 myenteric neurons in guinea-pig ileum in vitro. Each peptide evoked membrane depolarization associated with increased input resistance, enhanced excitability and suppression of hyperpolarizing after potentials. The effects of the peptides simulated slow synaptic excitation in the myenteric plexus and are consistent with a neurotransmitter or neuromodulatory function. PMID- 4043230 TI - DSP-4 lesioning prevents the enhancement of dopamine and 5-hydroxytryptamine mediated behavioural changes by repeated electroconvulsive shock. AB - DSP-4 (N-(2-chloroethyl)-ethyl-2-bromobenzylamine) a novel neurotoxin which destroys central noradrenaline neurones after peripheral injection was administered to rats (50 mg/kg X 2). This procedure did not alter activity responses to quipazine (7.5 mg/kg) or apomorphine (0.2 mg/kg) but prevented their enhancement by repeated electroconvulsive shocks (ECS X 10). This confirms that intact noradrenergic function is required for ECS-induced enhancement of 5-HT and dopamine mediated responses. Furthermore, DSP-4 is shown to provide a simple, effective alternative to centrally injected 6-hydroxydopamine for noradrenergic lesioning. PMID- 4043231 TI - Yohimbine can not exert its anticonvulsant action in genetically audiogenic seizure-prone mice. PMID- 4043232 TI - Ethanol preferentially stimulates dopamine release in the nucleus accumbens of freely moving rats. PMID- 4043233 TI - A centrally elicited respiratory stimulant effect by bombesin in the rat. AB - The effects of the tetradecapeptide bombesin on respiratory regulation in the rat were studied using a whole body plethysmographic model. Application of the peptide was made intracerebroventricularly (i.c.v.) as well as via microinjections into specific brainstem areas. I.c.v. injection (0.1-5 micrograms) resulted in a dose-dependent increase in tidal volume while respiratory frequency was decreased only at higher doses. The respiratory duty cycle remained unchanged while the respiratory drive was significantly increased. The respiratory effects were blunted by bilateral section of the tenth cranial nerve. Studies employing the occluded breath technique indicated a change in the threshold to afferent vagal signals while the time-setting for inspiration remained unchanged. Similar ventilation changes were elicited when the peptide was injected into the area of the nucleus ambiguous but not in several other areas of the brainstem. Such bombesin sensitive areas are consistent with a recent immunohistochemical study describing a dense pattern of immunoreactive somata in this area of the brainstem. The ventilatory stimulant effect seems to depend on an intact afferent vagal innervation. PMID- 4043234 TI - Diisopropylfluorophosphate inhibits choline efflux from the perfused rat hemidiaphragm. AB - Acetylcholine (ACh) synthesis by motor nerve terminals requires an adequate supply of its precursor, choline. The results reported here show that diisopropylfluorophosphate (DFP), an acetylcholinesterase inhibitor commonly used in ACh release studies, reduces the rate of endogenous choline efflux from the perfused rat hemidiaphragm. Perfusion of the isolated hemidiaphragm with 10 microM or 100 microM DFP reduced choline efflux by 39% and 69% respectively. DFP administration to rats (6 mg/kg) also lowered the in vitro release of choline by 33%. The rate of ACh release from hemidiaphragm preparations perfused with DFP was significantly lower than the rate of release from preparations perfused with physostigmine, an acetylcholinesterase inhibitor which had no effect on choline efflux. The addition of choline (10-30 micron) to the perfusion medium restored the rate of ACh release from DFP-treated hemidiaphragms but did not further elevated ACh release from physostigmine-treated preparations. These results demonstrate that DFP inhibits choline efflux from the isolated hemidiaphragm and further suggest that, by limiting the availability of choline for ACh synthesis, DFP reduces the rate of ACh release. PMID- 4043235 TI - Effect of GABA-T inhibitors on prolactin secretion in vitro. AB - A study was made of the effect of GABA-transaminase (GABA-T) inhibitors on the in vitro release of prolactin by pituitaries of male and female rats. Aminooxyacetic acid (AOAA) and gamma-acetylenic GABA (GAG) added to the incubation medium decreased prolactin release from both male and female rat pituitaries. Additive effects on prolactin release were only observed when male rat pituitaries were incubated with AOAA plus GABA. Prolactin concentration in the pituitary gland was also decreased by AOAA in both sexes. The present results lend support to the idea of an inhibitory action of GABA on prolactin release by the pituitary gland. PMID- 4043236 TI - Induction of artificial spermiation in the fresh water Clarias batrachus (Linn.) by clomiphene citrate. AB - Intramuscular thrice a week injections of clomiphene citrate (25 micrograms/0.5 ml/100 g body weight) were administered for a period of 3 months to the animals in the experimental group. The control group received 0.5 ml/100 g body weight of physiological saline throughout the period of experimentation (February - April). The control testes were in recrudescence in February, since spermatids and sperms came to appear in these testes from early March onwards. On the other hand, in the experimental group, as a result of drug administration, there was a steady increase in testicular size, and the spermatocytes begin to enlarge and mature into spermatids and sperms. This is to our knowledge, the first document of a commercially important male teleostean fish Clarias batrachus with high nutritive value being made to spermiate in the laboratory 4 months ahead of natural schedule, using a chemical inductor 'Clomid'. PMID- 4043237 TI - Short-term implantation of oestrogen into the anterior amygdaloid area of immature rats delays the first pubertal ovulation. AB - Unilateral implants containing oestradiol benzoate (OB) and cholesterol at the ratio of 1 + 4 were placed for 48 h either in the region of the anterior amygdaloid area (AAA) and nucleus of the lateral olfactory tract (NLOT) or in the anterior or posterior part of the mediocortical amygdala of immature 26-day-old female rats, and the age at vaginal opening and the first ovulation was recorded. Whereas implants located in the mediocortical amygdala did not influence the occurrence of ovulation or advanced it distinctively, implantation of OB into the AAA/NLOT resulted in a highly significant delay of the first pubertal ovulation that was associated with postpubertal persistent vaginal cornification in part of the rats. PMID- 4043238 TI - Acute effects of ethanol intake on the serum concentrations of parathyroid hormone, calcium and phosphate. AB - Several previous observations from animal and in-vitro studies indicate that both the acute and chronic ingestion of ethanol could affect calcium regulation but little data is available concerning the effects of ethanol in man. Twelve healthy male subjects drank 0.8 g ethanol/kg body weight in the form of whisky so that the serum ethanol concentrations reached an average of 17.4 +/- 2.5 (SD) mmol/l. At this time there were no significant differences for the serum concentrations of parathyroid hormone, calcium or phosphate. Thus, it appears that there is little acute effect on calcium homeostasis in man of a moderate rise of serum ethanol levels. PMID- 4043239 TI - Thyroidal thyroxine and triiodothyronine in autonomously functioning thyroid nodule and paranodular tissue. AB - Thyroidal thyroxine (T4), triiodothyronine (T3), thyroglobulin (Tg) and T4/T3 ratio were investigated in nodular and paranodular tissue from 16 patients with autonomously functioning thyroid adenomas. The concentration of T4 and T3 in the nodule were 97.7 +/- 20.5 (Mean +/- SE) and 10.2 +/- 2.4 micrograms/g wet weight (w.w.). Both iodothyronines were significantly lower in paranodular tissue (22.6 +/- 4.8 and 1.45 +/- 0.32 micrograms/g w.w., respectively), but with disproportionately decreased T3 which resulted in T4/T3 ratio (25.4 +/- 6.4) higher than in adenoma tissue (11.2 +/- 1.6). In patients with high normal or supranormal serum T3 concentration, thyroidal concentration of T3 in adenoma tissue was higher (15.6 +/- 5.0 vs. 6.3 +/- 1.2 micrograms/g w.w.) and T4/T3 ratio lower (8.05 +/- 2.1 vs. 13.2 +/- 1.9) than in patients with normal serum T3. The results suggest that thyroid release of T3 from adenoma is relatively higher than T4 in patients with autonomously functioning thyroid nodules and increased peripheral T3. PMID- 4043240 TI - Effects of osmotic shocks on the ultrastructure of different tissues and cell types. AB - This study deals with the effects of hyper- and hypo-osmotic media on the ultrastructure of four different types of cells and tissues: rat pheochromocytoma cells of line PC12, mouse Ehrlich ascites tumor cells, rat kidney cortex and intestine. Application of hyper-osmotic conditions induces in the nuclear compartment of the tested cell types a condensation of chromatin, a ruffling of the nuclear envelope with loosening of condensed chromatin from the lamina, and an apparent loss of nucleolar fibrillar component which disappears in a background of diffuse granular material. In hypo-osmotic media, there is a marked decondensation of chromatin and a fragmentation of the granular material of the nucleolus. As far as the cytoplasmic compartment is concerned, the electron density of the cytosol is markedly increasing when going from hypo- to hyper osmotic conditions and there is no vacuolization in hypo-osmotic media. In kidney cortex slices, application of hypo-osmotic shocks further results in a marked reduction of the extracellular space delimited by the infoldings of the tubular cells plasma membranes. These modifications are discussed in relation to the volume regulation process and the changes in ion concentration that occur in cells submitted to anisosmotic media. PMID- 4043241 TI - Perisinusoidal fat-storing cells are the main vitamin A storage sites in rat liver. AB - Highly purified sinusoidal (fat-storing, Kupffer and endothelial cells) and parenchymal cells were isolated to assess the cellular distribution of vitamin A in liver of adult vitamin A-sufficient rats. A modified simple procedure was developed for the purification of fat-storing cells from rat liver. This was achieved by a single centrifugation step in a two-layer density Nycodenz gradient. Endothelial and Kupffer cells were obtained from the same gradient and further purified by centrifugal elutriation. Reverse-phase HPLC analysis showed that fat-storing cells contained about 300-fold the amount of retinyl esters present in parenchymal cells on a mg cell protein basis. In fat-storing cells, the same retinyl esters, viz. retinyl palmitate, retinyl stearate and retinyl oleate, were present as in whole liver. It was also observed that, within 12 h after intravenous injection of chylomicron [3H]retinyl ester, most of the radioactivity had accumulated in the fat-storing cells. It is concluded that fat storing cells are the main storage sites for vitamin A in rat liver. PMID- 4043242 TI - Fibroblasts acquire beta-glucuronidase by direct and indirect transfer during co culture with macrophages. AB - Macrophages can transfer beta-glucuronidase directly to co-cultured fibroblasts during cell-to-cell contact as well as indirectly via receptor-mediated endocytosis. The degree of enzyme activity acquired by the deficient fibroblasts was determined by the ratio of donor to recipient cells and by the length of time for which cells were allowed to interact. Both mechanisms of transfer were efficient so that 70% of normal enzyme activity was restored to deficient fibroblasts after 24 h of co-culture. These observations show that macrophages have great potential as donor cells in replacement therapy for the treatment of inherited lysosomal enzyme deficiency diseases. PMID- 4043243 TI - Involvement of the Ca2+/phospholipid-dependent protein kinase in the G1 transit of T51B rat liver epithelial cells. AB - The G0----G1 and G1----S transitions (but not the intervening events) in the G1 phase of T51B rat liver epithelial cells in serum-stimulated confluent cultures required a high concentration of extracellular Ca2+ and were accompanied or immediately preceded by increases in the amount of EDTA-extractable protein kinase C, a Ca2+/phospholipid-dependent enzyme. Involvement of this Ca2+ dependent enzyme in the two Ca2+-dependent transitions was further indicated by the facts that 12-O-tetradecanoyl phorbol-13-acetate (TPA), a compound that stimulated protein kinase C from T51B cells even in the absence of Ca2+, enabled these cells to transit G1 in Ca2+-deficient medium, while a TPA analogue (4 alpha phorbol-12, 13-didecanoate (4 alpha-PDD) that did not stimulate the enzyme in cell-free preparations did not promote G0----G1 or G1----S transit in Ca2+ deficient medium. PMID- 4043244 TI - Heat-induced inhibition of DNA synthesis in L5178Y-S cells is reversed by caffeine. AB - Heating L5178Y cells for 15 min at 43 degrees C caused a decrease in [3H]thymidine incorporation, which could be reversed by post-treatment with 0.75 mM caffeine in an L5178Y-S (radiation-sensitive, heat-resistant) but not in an L5178Y-R (radiation-resistant, heat-sensitive) strain. The reversal was accompanied by a sparing effect of the treatment: survival of L5178Y-S cells increased by a factor of 1.5. The effect of combined (heat + caffeine) treatment of L5178Y-R cells was cumulative. PMID- 4043245 TI - High diadenosine tetraphosphate (Ap4A) level in germ cells and embryos of sea urchin and Xenopus and its effect on DNA synthesis. AB - Ap4A levels in sperms, eggs and different developmental stages of sea urchin (Psammechinus miliaris) and (Xenopus laevis) were determined by a method based on ATP measurement with luciferin/luciferase after splitting diadenosine 5',5''' P1,P4-tetraphosphate (Ap4A) into ATP and AMP. Appreciable storage pools of Ap4A were found in unfertilized eggs of Psammechinus and Xenopus as well as in sea urchin sperms. The actual Ap4A concentration of 28 microM in sperm represents the highest Ap4A level so far observed in eukaryotic cells. Upon fertilization an instant onset of de novo synthesis of Ap4A was demonstrated. Ap4A levels during early embryogenesis of P. miliaris and X. laevis (2.5-4 microM) are higher than those in exponentially growing mammalian culture cells and mammalian fetuses. Microinjection of Ap4A into unfertilized eggs of Psammechinus miliaris caused a 3 7 fold increase of DNA synthesis in comparison with mock-injected eggs. PMID- 4043246 TI - Proliferation-associated changes in in vitro mRNA translation in the HL60 cell line. AB - In order to characterize patterns of gene expression during the proliferation cycle of HL60 cells, we have analysed changes in the population of mRNA available for translation in vitro. HL60 cells were separated into cell cycle phases by centrifugal elutriation, monitoring the separation with flow cytometry. RNA was extracted from cell fractions highly enriched in G1, S or G2+M phases and translated in vitro. Translation products were analysed by two-dimensional electrophoresis followed by autoradiography. Autoradiograms were analysed by a computer-assisted method utilizing a drum-scanning microdensitometer. Spots were identified by their relative positions on the films and their relative intensity was estimated. Of the 159 peptides studied for cell cycle-associated changes in synthesis, nine showed phase-associated changes. The most significant changes were the accumulation of four peptides that showed maximal synthesis only in G2+M phases. An additional four peptides were synthesized maximally in both S and G2+M phases. One peptide showed maximal synthesis in S phase. These changes in gene expression suggest that these relatively abundant transcripts are regulated primarily at a quantitative level during proliferation and may be related to the doubling of structural proteins prior to mitosis. PMID- 4043247 TI - A marker of animal-vegetal polarity in the egg of the sea urchin Paracentrotus lividus. The pigment band. AB - We have examined the subequatorial accumulation of pigment granules (the so called 'pigment band') in the egg of the sea urchin Paracentrotus lividus, which constitutes an unambiguous marker of animal-vegetal polarity. Most of the reddish pigment granules are situated at the periphery of the egg. They exhibit occasional saltatory movements and can aggregate into large patches. Pigment granules are retained as a band in the isolated cortex when the egg surface complex is isolated by shearing eggs attached to polylysine-coated surfaces with calcium-free isotonic solutions. Pigment granules remain as the main vesicular component of fertilized egg cortices or of unfertilized egg cortices perfused with calcium to provoke cortical granule exocytosis. They may be anchored to the isolated cortex through associations with the plasma membrane and with an extensive subsurface network of rough endoplasmic reticulum (rough ER). Pigment granules contain antimonate-precipitable calcium and, in this respect and many others, resemble acidic vesicles recently identified in the cortex of unpigmented sea urchin eggs. We discuss the similarities observed between granules and acidic vesicles in various urchin egg species and their possible functions. PMID- 4043248 TI - Receptor-mediated uptake of horseradish peroxidase in innervated and denervated skeletal muscle. AB - The in vitro uptake of [3H]inulin and horseradish peroxidase (HRP) has been studied in innervated and 6 days denervated extensor digitorum longus muscle of the mouse. Both markers were taken up at a higher rate in denervated muscle. The increase in uptake after denervation was, however, larger for HRP than for [3H]inulin. After 2 h incubation at 37 degrees C, pH 7.3, in the presence of equimolar concentrations of HRP and [3H]inulin (approx. 2.1 microM), the uptake of HRP was approx. 8 times as great as the uptake of [3H]inulin in the same innervated muscles. In denervated muscle the HRP uptake was approx. 19 times as great as the [3H]inulin uptake in the same muscles. Various possible explanations of these differences in uptake have been considered and tested experimentally. [3H]Inulin uptake in skeletal muscle has previously been shown to obey bulk kinetics. The present investigation shows the HRP uptake to obey saturation kinetics. The HRP uptake shows dependency on divalent cations and is reduced if incubation is carried out at pH 6.4. The uptake of HRP, when used at a low, non saturating concentration (10 micrograms/ml approx. 0.25 microM), is inhibited greater than or equal to 60% by yeast mannan (0.1 mg/ml), ribonuclease B (0.1 mg/ml, approx. 7.4 microM), mannose (30 mM), monodansylcadaverine (1 mM), chloroquine (100 microM), trifluoperazine (25 microM) or maleic acid (2 mM). It is concluded that HRP is taken up in innervated and denervated skeletal muscle by a process of receptor-mediated endocytosis and that this uptake is under neurotrophic control. PMID- 4043250 TI - Low pH value of pericellular medium as a factor limiting cell proliferation in dense cultures. AB - An attempt was made to determine the role of metabolic acidification of pericellular medium in regulating cell proliferation. A method of measuring the pH of pericellular medium at a distance exceeding a Debye radius of 5-10 A from the cell surface (pHp) was developed. The values of pHp and pH measured in the medium at a distance of greater than 1 cm from cells (pHm) were found to differ, depending on the cell population density. At a density of at least 7 X 10(5) cells/cm2 (maximum saturation density) and at pHm 7.4-7.6, pHp reached a value of approximately 6.5. It was found that pHm 6.5 was unfavorable for cell proliferation in sparse cultures, where pHm and pHp were equal. Based on these findings, low pHp as revealed in the present work using dense cultures at optimal pHm can be considered to be a limiting factor for cell multiplication. PMID- 4043249 TI - Intracellular calcium redistribution during mating in Chlamydomonas reinhardii. AB - Gametes of the unicellular green alga Chlamydomonas reinhardii recognize and adhere to cells of the opposite mating type by flagellar contact. Adhesion between these specialized organelles signals a rapid series of mating events which result in gamete fusion. The sequence of morphological changes (flagellar tip activation, cell wall loss, and mating structure elongation), which occur as a consequence of the sexual signalling, have been characterized. The signalling mechanisms have, however, not been defined. Calcium is known to be involved during fertilization of animal species. Increased intracellular free calcium, which can be achieved either by calcium influx or by mobilization of ions from intracellular stores, has been observed during activation of both eggs and sperm. A recent report by Bloodgood & Levin that gametes of C. reinhardii preloaded with 45Ca showed a transient increase in Ca efflux following mating, suggests that intracellular Ca redistribution may also accompany mating in this algal species. We have used X-ray microanalysis to analyze the subcellular distribution of bound calcium during mating in Chlamydomonas reinhardii. X-ray maps reveal that calcium is sequestered in discrete granules within the gamete cell body prior to mating and that during activation and cell fusion, calcium is diffuse throughout the cell. This suggests the possibility that calcium serves as a second messenger in this species. PMID- 4043251 TI - Evidence for regulation of actin synthesis in cytochalasin D-treated HEp-2 cells. AB - In HEp-2 cells treated with 0.2 or 2.0 microM cytochalasin D (CD), the relative rate of actin synthesis increased for about 12 h and then reached a plateau; this increase was suppressed by actinomycin D (AD). When CD was washed from cells which had been treated for 20 h, the elevated rate of actin synthesis declined to the control value within ca 4 h, as the actin-containing cytoskeletal components rearranged by CD recovered their normal morphology. Subsequently, actin synthesis was depressed below control values for a prolonged period; during recovery from 2 h treatment with CD, this depression was of much shorter duration. Re-addition of CD to cells after a 3 h recovery period again induced the cytoskeletal alterations characteristic of CD treatment but did not reverse the prior decline in the rate of actin synthesis. In HEp-2 cells treated with cycloheximide during exposure to CD for 20 h, the relative rate of actin synthesis measured after removal of cycloheximide was twofold higher than with CD alone and such cells exhibited a twofold slower decline in the rate of actin synthesis during recovery from CD in the continued presence of cycloheximide. These effects of cycloheximide, which resemble observations on "super-induction", suggest that actin synthesis in CD-treated and recovering HEp-2 cells may be regulated by a repressor protein. The possibility that the proposed repressor protein is actin and that actin may thus be a feedback inhibitor of its own synthesis is discussed. PMID- 4043252 TI - Autophagic sequestration of [14C]sucrose introduced into isolated rat hepatocytes by electrical and non-electrical methods. AB - Isolated rat hepatocytes were found to become permeable to [14C]sucrose at 0 degree C under three different conditions: Immediately following their liberation from the collagenase-perfused liver. Following a short incubation under hypoxic conditions. After electropermeabilisation. All three conditions were characterised by the formation of small protuberances (blebs) indicative of localised cell surface damage, and it is possible that the stretched plasma membrane of such blebs acted as a high-permeability region. Disappearance of blebs and restoration of normal plasma membrane impermeability could be achieved by a short (15 min) incubation at 37 degrees C. It could be shown that [14C]sucrose introduced into rat hepatocytes by non-electrical means was autophagically sequestered at the same rate as [14C]sucrose introduced electrically. In both cases the sequestration was inhibited by the specific autophagy inhibitor 3-methyladenine to a similar extent. The subcellular distribution of sequestered isotope in metrizamide/sucrose density gradients was found to be independent of the conditions of its introduction into cells. PMID- 4043253 TI - Cell growth and cell proliferation may be dissociated in the mouse uterine luminal epithelium treated with female sex steroids. AB - The mouse uterine epithelium under various hormonal regimes is a good system to identify biochemical events associated with cell growth, DNA synthesis and cell division. This is because estradiol-17 beta stimulates the cells to undergo a synchronized wave of DNA synthesis and cell division. Estriol, on the other hand, also stimulates DNA synthesis but because of the rapid loss of this hormone from the tissue some of the cells abort, giving a constant epithelial cell number. Three days of progesterone pretreatment, however, completely suppresses the estradiol-17 beta-induced wave of DNA synthesis and cell proliferation. Using these hormonal treatments we have shown that both estradiol-17 beta and estriol stimulate protein and rRNA synthesis with the concomitant increase of protein and rRNA per mg of DNA. These macromolecules accumulated in direct proportion to the fraction of cell committed to DNA synthesis. Estriol, however, did not sustain the growth responses and at the peak of DNA synthesis both rRNA and protein synthesis had returned to control levels. Progesterone pretreatment, despite inhibiting the proliferative response, failed to inhibit any of the estradiol-17 beta-induced increases in protein and rRNA synthesis. Indeed 12 h after estradiol 17 beta injection the cells had identical protein and rRNA contents, regardless of whether they had been exposed to progesterone or not. The present data therefore suggests that in the uterine epithelium cell growth as defined by protein and rRNA accumulation and DNA synthesis represents two independently regulated pathways. PMID- 4043254 TI - Partial purification and characterization of mitotic factors from HeLa cells. AB - Extracts from mitotic HeLa cells, when injected into Xenopus laevis oocytes, exhibit maturation-promoting activity (MPA) as evidenced by the breakdown of the germinal vesicle and the condensation of chromosomes. In this study we have attempted to purify and characterize these mitotic factors. When 0.2 M NaCl soluble extracts of mitotic HeLa cells were concentrated by ultrafiltration and subjected to affinity chromatography on hydroxylapatite followed by DNA cellulose, the proteins with MPA eluted as a single peak and their specific activity was increased approx. 200-fold compared with crude extracts. The molecular weight of the mitotic factors was estimated to be 100 kD as determined by chromatography on Sephacryl S-200. SDS-PAGE of the partially-purified mitotic factors indicated the presence of several polypeptides ranging from 40-150 kD with a major band of about 50 kD. The majority of these polypeptides were found to be phosphoproteins as revealed by 32P-labeling and autoradiography. Very little or no phosphorylation was observed at the 50 kD band. Several of these polypeptides were reactive with mitosis-specific monoclonal antibodies, MPM-1 or MPM-2, as shown by immunoblots of these proteins but the major polypeptide band at 50 kD was not. Removal of the immunoreactive polypeptides by precipitation with these antibodies did not destroy the MPA. The MPA of the crude or the partially-purified mitotic factors was destroyed by injection of (but not pretreatment with) alkaline phosphatase within 45 min after injection of mitotic factors. These results are discussed in terms of a possible role of phosphorylation-dephosphorylation of non-histone proteins in the regulation of mitosis and meiosis. PMID- 4043256 TI - Persistence of the competent state in mouse fibroblasts is independent of c-fos and c-myc expression. AB - Induction of competence in quiescent fibroblasts by platelet-derived growth factor (PDGF) is accompanied by a dramatic increase in the expression of c-fos and c-myc genes. However, the maintenance of the competent state and progression through G1 does not require high expression of these proto-oncogenes. These results suggest that the induction of c-fos and c-myc by growth factors in quiescent fibroblasts may be required to render the cells competent for progression. PMID- 4043255 TI - Coordinate release of myosin and a high molecular weight microtubule-associated protein from PC12 cytoskeletons by ATP. AB - The association of two high molecular weight (HMW) structural proteins with the cytoskeletons of rat pheochromocytoma cells, PC12, is regulated by ATP and other nucleotides. Exposure of PC12 cytoskeletons to ATP resulted in the selective solubilization of two HMW proteins, identified as myosin and a 280 kD microtubule associated protein. These two proteins were rapidly released from the cytoskeleton following incubation with ATP, GTP, CTP, and ADP; non-hydrolysable ATP analog caused protein release to a less marked extent. The effect of the latter two nucleotides indicated that the release of the myosin and the HMW microtubule-associated protein was likely to be the result of nucleotide-induced conformational changes in one or both proteins. Myosin and the HMW microtubule associated proteins interact with actin in vitro in a nucleotide-sensitive manner. The present data demonstrate that similar interactions are likely to exist within the intact cytoskeleton and suggest that the associations of these structural proteins with the cytoskeleton are regulated by common mechanisms. The results also suggest that the cells may differentially regulate the stability of a subset of these structural proteins in their interactions with other cytoskeletal elements. PMID- 4043257 TI - Erythroid progenitors in Rauscher leukemia virus variant-A-induced erythropoietic dysplasia in mice. AB - In vitro erythropoiesis by bone marrow and spleen cells was assessed in normal mice and during progression of Rauscher leukemia virus, variant-A (RLV-A) disease in mice. As RLV-A disease progressed from early through terminal stages, there was a marked increase in the numbers of in vitro splenic CFU-E and BFU-E. Conversely, bone marrow CFU-E and BFU-E demonstrated a concomitant decrease in numbers with disease progression. At no time were erythropoietin-independent (endogenous) erythroid colonies generated. The results suggest that compartmental alterations in erythroid precursors occur during progression of RLV-A. PMID- 4043258 TI - A technique for the daily examination of spleen colonies in mice. AB - We have developed a surgical method and an insertable device for viewing the daily changes in number, shape, and development of hemopoietic spleen colonies in mice. With it we have been able to follow the spleen colony changes in individual animals over the period when macroscopic or moderately magnified counts of spleen colonies are customarily made. We have found that about half of the spleen colonies present on day 8 after transplantation do remain through day 12, while an approximately equal number disappear during this period. Further, the colonies that disappear are replaced by an equal or larger number of newly developing colonies at roughly the same temporal sequence as their disappearance. We speculate that these late-appearing colonies may be late arrivals from the recipient's previously seeded bone marrow. PMID- 4043259 TI - Stimulation of normal rat bone marrow fibroblast proliferation by sera from leukemic Fischer rats. AB - Fibroblast hyperplasia and accumulation of fibrous material in the bone marrow of patients with idiopathic (primary) or secondary myelofibrosis (MF) is believed to result from a reaction by marrow fibroblasts to an altered marrow microenvironment, the alteration being potentiated by abnormal hemic cells. We investigated the hypothesis that humoral factors might contribute to fibroblast overgrowth in MF by using an animal model, aged Fischer rats, where MF frequently occurs with leukemia. Sera from leukemic rats and leukemic cell conditioned media (CM) were assayed for enhancement of normal rat marrow fibroblast proliferation in a culture system where fibroblasts form discrete, adherent colonies. Our results demonstrated that: leukemic sera induced a 170% increase in total fibroblast colony numbers and a 325% increase in colonies containing more than 80 cells, stimulation of fibroblast growth was leukemia related since sera from rats with transplanted leukemia enhanced marrow fibroblast proliferation, leukemic cell CM did not contain a growth factor for marrow fibroblasts, sera from leukemic rats and 2-mercaptoethanol were additive in enhancing marrow fibroblast proliferation and probably act by different mechanisms, and leukemic rat sera was less effective as a colony-stimulating factor than normal rat sera, a condition mimicked when leukemic and normal spleen CM were compared. This is the first time that a serum component has been implicated in the pathogenesis of MF; our work may contribute to understanding the mechanism involved when MF occurs as a complication of leukemia. PMID- 4043260 TI - Preparation of human erythropoietin for tissue culture. AB - A simple two-step procedure has been developed for the production of human urinary erythropoietin suitable for tissue culture use. Lyophilized human urinary protein was fractionated by phenyl-Sepharose chromatography, the erythropoietin binding in 2 M lithium chloride and being eluted by an ascending linear gradient to 6 M guanidine hydrochloride. The erythropoietin was further purified by ethanol (75% vol/vol) precipitation. This two-step procedure resulted in a 25 fold purification of erythropoietin with a 50% recovery of the starting activity. The erythropoietin preparation was suitable for use in murine or human cultures, being free of protease activity, inhibitory factors, colony-stimulating factors, and erythroid-enhancing activities. PMID- 4043261 TI - Visualization of fluorescent erythrocytes in the microcirculation. AB - Erythrocytes loaded internally with FITC-BSA can be readily visualized in the microcirculation by using a television camera and a fluorescence microscope. Flow properties of the erythrocytes and their adherence to the vascular endothelium or erythrophagocytic cells can be observed. This procedure should also be useful to delineate the microcirculation under circumstances where infused free FITC-BSA can escape into the interstitial tissue. PMID- 4043262 TI - Independence of megakaryocyte number and size in long-term cultures of normal mouse marrow. AB - Megakaryocytopoiesis was evaluated in long-term cultures of normal murine marrow to determine whether the number and size of megakaryocytes were independent or interdependent. Numbers of megakaryocytes and granulocytes varied widely in different experiments, due, in part, to varying concentrations of hydrocortisone in the culture medium. The sizes of acetylcholinesterase-positive cells were the same in cultures with as much as a 20-fold difference in megakaryocyte numbers. These results indicate that, in the closed culture system containing normal stromal cells, megakaryocyte size and number are not reciprocal as they were in many previously reported cultures of S1/S1d mouse marrow. The results suggest that separate stromal functions may determine precursor cell proliferation and nuclear endomitosis in megakaryocytes in vitro. The relationship of these findings to regulation of megakaryocytopoiesis in vivo remains speculative. PMID- 4043263 TI - Increased 2,5-adenylate synthetase activity in the spleens of BALB/c mice during hypoxia-stimulated erythropoiesis. AB - In response to prolonged, intermittent exposure to hypoxia, the spleens of adult BALB/c mice displayed an initial increase and subsequent decrease in erythropoietic activity. The enzyme 2,5-adenylate synthetase was assayed during this period, and a direct relationship was found between the rate of red cell production and enzyme activity; that is, 2,5-adenylate synthetase activity was maximum in the spleen cell populations that contained the largest number of nucleated erythroid cells and minimum in those populations that contained the fewest nucleated erythroid cells. In contrast to this finding, synthetase activity was inversely related to the number of lymphocytes present in these spleen cell populations. On the basis of these observations, it appears that 2,5 adenylate synthetase is present in nucleated erythroid cells. If active in late erythroblasts, 2,5-adenylate synthetase may function as an inhibitor of DNA synthesis and/or hemoglobin synthesis. PMID- 4043264 TI - Purification of human urinary erythropoietin on controlled-pore glass and silicic acid. AB - Erythropoietin (Epo) has been isolated from raw human urine of anemic patients by controlled-pore glass and silicic acid chromatography. A purification factor of not less than 100-fold and recovery of about 80% of activity was routinely achieved. The resulting Epo preparation is active both in vivo and in vitro and can be neutralized by an antibody to human Epo indicating the native state and identity of the isolated Epo molecule. The preparation is stable at near neutral pH and is amenable to further purification. PMID- 4043265 TI - Cyclosporin-A radioimmunoassay: a modified method for whole blood determination. AB - Cyclosporin-A levels were determined by radioimmunoassay in plasma or whole blood, using split samples collected from patients receiving this agent as the only form of immunosuppression following allogeneic bone marrow transplantation. In the plasma assay the temperature at which centrifugation took place was critical since the mean levels were approximately 30% higher with separation at 37 degrees C in comparison to 20 degrees C or lower. Furthermore, the level in whole blood samples was 2.4 times higher than that from the matching serum. In addition, anticoagulated blood that had been frozen and then thawed was technically more difficult to pipette and resulted in a recovery of only 83% of the cyclosporin when compared with assay using fresh blood. In contrast, consistent measurements were obtained either when whole blood was stored at 4 degrees C and then well mixed and diluted in buffer immediately prior to use or when such buffered samples were frozen and thawed immediately before analysis. The latter modifications render the whole blood assay a practical and reliable means for monitoring cyclosporin-A concentrations and may avoid excessive and the potentially nephrotoxic levels achieved when plasma levels are held in ranges previously considered therapeutic. PMID- 4043266 TI - Characterization of murine erythropoietin. AB - Although erythropoietins from human and sheep sources have been purified, a mouse erythropoietin remains essentially uncharacterized despite the fact that the mouse is most commonly used to assay for erythropoietin. Because other murine growth factors may have erythropoietic activity it will be essential to compare these with erythropoietin from murine sources rather than from other species. Here we compare the physicochemical properties and some of the bioactivities of erythropoietins from anemic mouse serum and human urine in parallel fractionations. Both molecules showed similar molecular weights (40-45,000) by gel filtration and similar retention characteristics on reverse-phase high performance columns. However, they differed in their relative solubility in ammonium sulfate, hydrophobicity on phenyl-Sepharose, and in their ability to bind to a phenyl-boronate agarose column. Despite these differences the two molecules stimulated the same number of CFU-E in the mouse fetal liver assay and did so with similar dose-response relationships. The data indicate that putative murine erythropoietic stimuli must be compared with murine erythropoietin and not human urine erythropoietin before concluding, on the basis of fractionation results, that a factor is different from erythropoietin. PMID- 4043267 TI - Separation of human blast progenitors from granulocytic, erythroid, megakaryocytic, and mixed colony-forming cells by "panning" on cultured marrow derived stromal layers. AB - Primitive myeloid progenitor cells will adhere to stromal feeder layers of human bone-marrow-derived adherent cells grown in the presence of methylprednisolone (MP+ layers). These progenitors form colonies of blast cells on the MP+ stromal layers, but not on stromal layers grown in the absence of MP (MP- layers). The present study was designed to determine whether this failure of colony formation was caused by inability of the progenitors to adhere to the MP- layers or inability to proliferate in their presence. We also compared the capacities of the blast progenitors to adhere to MP+ and MP- stromal cells with those of mixed (GEMM-CFC), erythroid (BFU-E), megakaryocytic (Mk-CFC), and granulocyte macrophage (GM-CFC) colony-forming cells. Incubation of bone marrow mononuclear cells with MP+ stromal layers removed 90% of the blast progenitors, but did not remove the majority of the GEMM-CFC, BFU-E, Mk-CFC, and GM-CFC; incubation of bone marrow mononuclear cells with MP- stromal layers did not remove the blast progenitors or the GEMM-CFC, BFU-E, Mk-CFC, and GM-CFC. Thus, the blast progenitors adhere to MP+ stromal feeder layers, but not to MP- stromal layers. In this respect they differ from the other more mature colony-forming cells that do not show any marked tendency to adhere to either type of stromal layer. PMID- 4043268 TI - Hemopoiesis in cellulose ester membrane: characterization of the epilayer responsible for recognition and lodgement of hemopoietic cells. AB - Following intraperitoneal (i.p.) insertion of cellulose ester membranes in the mouse, the membranes develop a cellular coat that after sublethal irradiation and i.p. infusion of marrow cells supports the growth of hemopoietic colonies. The uppermost layer of this cellular coat (the epilayer) becomes extremely attenuated and develops numerous microvilli that interact with infused cells to trap and lodge them. This phenomenon is analogous to specific lodging of hemopoietic stem cells in the marrow after bone marrow transplantation. The mechanism of this interaction is not clear, but attention has recently focused on specific interaction of sugar residues of membrane glycoproteins. We have characterized the free surface of this epilayer with various lectins, glycosylated ferritins, and antifactor VIII antibody. There is strong binding of the three lectins Ricinis communis agglutinin (RCA II), phytohemagglutinin (PHA), and wheat germ agglutinin (WGA), but not Ulex europeaus agglutinin, concanavalin A, the tested glycosylated ferritins, or antifactor VIII antibody. The highest density of binding is on microvilli. Since marrow sinus endothelium also strongly binds RCA II, PHA, and WGA, it is possible that the sugar residues of membrane glycoproteins specifically binding these lectins are responsible for cellular and molecular recognition and transport across the epilayer. PMID- 4043269 TI - Convergent strabismic amblyopia in cats. AB - Experiments were carried out to determine the effects of different types of experimental strabismus on the acuities of retinal ganglion cells. Six kittens were raised from twenty-one days of age with an esotropia surgically induced by myectomy of the lateral rectus muscle and a large portion of the superior oblique muscle. The results are compared with those, previously reported, from five other cats also made esotropic, but by tenotomy of the lateral rectus. All animals tested behaviourally were amblyopic in the strabismic eye. For square wave gratings, the visual acuities were 1.0 to 2.5 cyc/deg through the strabismic eye compared with 6.0 to 7.5 cyc/deg through the non-deviating eye. The cut-off spatial frequencies were determined for 132 brisk sustained cells from five of the myectomized strabismic cats. There was a loss of approximately 20% in cut-off spatial frequency when compared with both normal and tenotomized cats. A correlate of the physiologically observed difference between the tenotomized cats and the myectomized cats was also found in the morphology of cells in the lateral geniculate nucleus. The tenotomized cats showed no evidence of cell shrinkage in laminae receiving a projection from the amblyopic eye whereas in the myectomized cats large differences were observed in cell cross-sectional areas between laminae receiving input from the amblyopic eye and those receiving input from the non-deviating eye. Together, these findings indicate that the presence of a neural deficit in the retina of strabismic cats is associated with the actual removal of extra-ocular muscle and probably has little to do with the optical quality of images arriving at the retina. PMID- 4043271 TI - Responses of cerebellar fastigial neurons to single muscle activation. AB - In lightly barbiturized cats, the discharges of neurons in the cerebellar fastigial nucleus (CBM) were recorded while single muscles in ipsilateral forelimb were activated by direct stimulation. The aim was to verify whether CBM cells could selectively detect the activity of afferent fibers from a muscle or a joint and to compare the various response characteristics of the rostral and the caudal division of the nucleus, which are known to control a different muscular periphery. Six muscles were routinely tested, two axial, two proximal and two distal ones. A good percentage of neurons in both partitions of the nucleus responded to the muscles tested (53% and 48% in the rostral and caudal part, respectively). In the rostral part of CBM a large proportion of cells (78% of those responsive) were influenced by one or more muscles having either the same function (the extensors or flexors) or acting on the same joint. Many such neurons showed a marked capability to respond to activation of distal muscles and a prevalence of inhibitory responses mainly on contraction of extensor and axial muscles. In the caudal division of the nucleus, 47% of the responsive cells displayed a stereotyped discharge pattern (excitatory or inhibitory) in response to activation of any tested muscle. In contrast to the rostral CBM the incidence of responses to proximal and distal muscles was about equal in the caudal CBM and a majority of neurons had excitatory responses to flexor muscle contraction. The latencies of the excitatory effects ranged from 8 to 53 ms in rostral and 9 up to 69 ms in caudal CBM.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4043270 TI - Classical conditioning of the nictitating membrane response of the rabbit. III. Connections of cerebellar lobule HVI. AB - We report the connections of cerebellar cortical lobule HVI in the rabbit. We have studied the anterograde and retrograde transport of wheatgerm-agglutinated horseradish peroxidase (WGA-HRP) following its injection into HVI to reveal efferent and afferent connections. All of the cases showed strong anterograde transport to the anterior interpositus nucleus (AIP) - indicating that this is the major efferent target of HVI. Retrogradely labelled cells were found in the inferior olivary, spinal trigeminal, lateral reticular, inferior vestibular and pontine nuclei. Within the olive, the medial part of the rostral dorsal accessory olive (DAO) and the adjacent medial part of the principal olive (PO) were consistently labelled in all cases. This area is known to receive somatosensory information from the face and neck. There was no projection to the hemispheral part of lobule VI from visual parts of the olive within the dorsal cap and medial parts of the medial accessory olive. Likely sources of visual and auditory information to HVI are the dorsolateral basilar pontine nuclei and nucleus reticularis tegmenti pontis, which were densely labelled in all cases. These anatomical findings are consistent with the suggestion that, during NMR conditioning, information related to the periorbital shock unconditional stimulus (US) may be provided by climbing fibres to HVI and light and white noise conditional stimulus (CS) information may be supplied by pontine mossy fibres. PMID- 4043273 TI - Simple cells in cat striate cortex: responses to stationary flashing and to moving light bars. AB - Cells in the simple family respond to a moving light bar with an average response histogram that is most commonly unimodal (single peak: encounter frequency, 64%) and less commonly bimodal (33%) or trimodal (3%). The mean width of the principal response peak given by hypercomplex I cells is narrower than that of simple cells and they have a lower mean optimal stimulus velocity. In a series of 74 cells (simple, 47; hypercomplex I, 27), detailed comparison of the spatial relations between the response peaks to the moving bar and the subregions to the stationary flashing bar led to the concept of a boundary response. The term "boundary response" refers to an isolated response peak occurring as a moving light bar leaves an OFF subregion that is the last in the sequence of subregions traversed by the bar. The presence of a boundary response leads to an apparent discrepancy between the number of response peaks to a moving light bar and the number of ON subregions in the static-field plot. The boundary response is necessarily completely direction selective. A detailed comparison of the properties of cells as revealed by hand and quantitative methods showed a very good agreement between the two methods in respect to the assignment of cells to the simple, B- and complex cell families. There were, however, serious discrepancies in respect to the receptive field organization of cells in the simple family.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4043272 TI - Spatial organization of subregions in receptive fields of simple cells in cat striate cortex as revealed by stationary flashing bars and moving edges. AB - For each of 74 simple striate cells a quantitative analysis was made of the width dimensions and spatial arrangements of the subregions responding either at light on (ON subregion) or at light off (OFF subregion). It was concluded that every cell has at least two and no more than four subregions. Cells with two subregions (57%) were much more commonly encountered than those with three (32%) or four (11%). For most cells adjacent subregions were significantly overlapped, the region of overlap responding both at light on and at light off. In the case of cells with two subregions, the overlap averaged 32% of the overall width of the two subregions. Despite the degree of the overlap, there was, on this basis, still a large measure of discrimination between cells in the simple family and those in the B-cell and complex families. In general the receptive field profiles of cells with three and four subregions were only marginally wider than those with only two subregions. In any given receptive field, the subregions tend to be roughly equal in width so that, in cells with four subregions, the subregions are, on the average, distinctly narrower than they are in cells with only two. Hypercomplex I cells tend to have receptive fields with three and four subregions much more commonly than simple cells and these cells are encountered much more frequently in cortical cell laminae 2, 3 and 4 than in lamina 6. In lamina 6 most of the cells in the simple family have receptive fields with only two subregions. The width dimensions and spatial sequences of the response peaks to moving light and dark edges were quantitatively analyzed in response profiles prepared from 82 cells. In general, for any given receptive field, the response peaks to moving edges have a one-to-one correspondence with the subregions to a stationary flashing bar. When this is not the case, the tendency is for the number of response peaks to edges to be less than the number of subregions rather than more. PMID- 4043274 TI - The organization of eye and limb movements during unrestricted reaching to targets in contralateral and ipsilateral visual space. AB - The spatial and temporal organization of unrestricted limb movements directed to small visual targets was examined in two separate experiments. Videotape records of the subjects' performance allowed us to analyze the trajectory of the limb movement through 3-dimensional space. Horizontal eye movements during reaching were measured by infrared corneal reflection. In both experiments, the trajectories of the different reaches approximated straight line paths and the velocity profile revealed an initial rapid acceleration followed by a prolonged period of deceleration. In Experiment 1, in which the target light was presented to the right or left of a central fixation point at either 10 degrees or 20 degrees eccentricity, the most consistent differences were observed between reaches directed across the body axis to targets presented in the contralateral visual field and reaches directed at ipsilateral targets. Ipsilateral reaches were initiated more quickly, were completed more rapidly, and were more accurate than contralateral reaches. While these findings suggest that hemispherically organized neural systems are involved in the programming of visually guided limb movements, it was not clear whether the inefficiency of the contralateral movements was due to reaching across the body axis or reaching into the visual hemifield contralateral to the hand being used. Therefore, in Experiment 2, the position of the fixation point was varied such that the effects of visual field and body axis could be disembedded. In this experiment, the kinematics of the reaching movement were shown to be independent of the point of visual fixation and varied only as a function of the laterality of the target position relative to the body axis. This finding suggests that the kinematics of a reaching movement are determined by differences in the processing of neural systems associated with motor output, after the target has been localized in space. The effect of target laterality on response latency and accuracy, however, could not be attributed to a single frame of reference, or to a simple additive effect of both. These findings illustrate the complex integration of visual spatial information which must take place in order to reach accurately to goal objects in extrapersonal space. Comparison of ocular and manual performance revealed a close relationship between movement latency for both motor systems. Thus, rightward going eye movements to a given target were initiated more quickly when accompanied by reaches with the right hand than when they were accompanied by reaches with the left hand.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 4043275 TI - Efferent connections of area 20 in the cat: HRP-WGA and autoradiographic studies. AB - Following injections of horseradish peroxidase-wheat germ agglutinin conjugate (HRP-WGA) and tritiated leucine into area 20 of the cat, terminal labeling was observed in visual areas 19, 21, the splenial visual area, the lateral suprasylvian area as well as in premotor, association and limbic related cerebral cortical regions. Labeled terminals in the subcortex were distributed in the caudate nucleus, the claustrum, the putamen, the anterior ventral nucleus, the intralaminar nuclei, the caudal division of the intermediate lateral nucleus, the lateralis posterior-pulvinar complex, the parvocellular C laminae of the dorsal lateral geniculate nucleus and the ventral lateral geniculate nucleus. In HRP-WGA preparations, retrogradely labeled somata were observed in these regions with the exception of certain subcortical structures. The projections are discussed with respect to the possible role area 20 plays in the cortical control of pupillary constriction. PMID- 4043276 TI - Distribution of neurons related to a hindlimb as opposed to forelimb movement in the monkey premotor cortex. AB - Single cell recordings were made from the premotor cortex (lateral part of area 6) of a monkey trained to perform either a distal hindlimb or forelimb movement separately. Out of 175 movement-related neurons, 59 neurons showed modulation of activity only prior to the hindlimb movement, and the majority of them was distributed in a focal region around the superior precentral sulcus, several mm posteromedial to the genu of the arcuate sulcus. The hindlimb focus was separate from a focal region for forelimb movement-related neurons, which lay immediately posterior to the genu of the arcuate sulcus. PMID- 4043277 TI - Binocular depth perception in the cat following early corpus callosum section. AB - The role of the corpus callosum in the mediation of binocular depth perception was examined by measuring monocular and binocular depth discrimination thresholds in cats which had undergone section of the corpus callosum shortly after birth. Three kittens had the posterior callosum sectioned at the age of eleven days. A fourth kitten underwent a sham operation and one additional animal served initially as an unoperated control. Monocular and binocular depth thresholds were measured for all kittens when they were between three and five months old. Although there was some individual variability, none of the callosum-sectioned kittens showed any deficits of binocular depth perception relative to normal animals. The initially unoperated kitten had its callosum sectioned at five months and was retested following surgery. Its performance did not change from preoperated levels. Finally, the three neonatal callosum-sectioned kittens underwent section of the optic chiasm when they were six months old, causing a complete breakdown in binocular depth discrimination. The results are interpreted to indicate that although the corpus callosum may be a sufficient pathway for the maintenance of stereopsis in cat, it is not necessary. PMID- 4043278 TI - Cutaneous facilitation of transmission in Ib reflex pathways in the human upper limb. AB - Group I effects from wrist extensors to flexors, i.e. an early inhibition followed by a relative facilitation which are thought to be Ia and Ib in origin respectively, were compared in control conditions and when preceded by a weak cutaneous stimulation. Stimulating the skin of the dorsal side of fingers II-III, which did not modify the test reflex size when applied alone, increased Ib facilitation. By contrast this Ib effect was not changed by stimulation of the skin of the palmar side. It has previously been shown that heteronymous Ib inhibition in the lower limb during voluntary contraction is facilitated by cutaneous stimulation from restricted receptive fields. Thus, present results lend support to the idea that cutaneous facilitation of transmission in Ib reflex pathways might be functional in curtailing exploratory movements. PMID- 4043279 TI - Properties of end-zone inhibition of hypercomplex cells in cat striate cortex. AB - The response properties of 96 striate cells in anaesthetized and paralyzed cats were examined by using narrow optimally-oriented light bars moved in the preferred direction at optimal velocity. The bar was lengthened systematically at both ends to plot and analyze bilateral length-response curves. We found a linear relationship between the maximum slope of the inhibitory phase of the curve and the strength of the end-zone inhibition for both cell families: simple and B cells. This observation indicates that the length of the two end-zones as given by a bilateral length-response curve is approximately constant regardless of the strength of the end-zone inhibition for a change in the strength of the inhibition from 10 to 100%. PMID- 4043280 TI - Spinal cord grafts in oculo: survival, growth, histological organization and electrophysiological characteristics. AB - Fetal spinal cord tissue was grafted to the anterior chamber of the eye of adult recipients. Transverse segments from the cervical and high thoracic levels were divided in halves which were grafted directly or further divided into ventral horn and dorsal horn parts before grafting. Survival and intraocular growth was monitored through the cornea. Grafts from E14 to E16 grew to final sizes several times the initial size. The final size of E17 grafts was approximately similar to the initial size, while the final size of E18 and E19 grafts was considerably smaller than the size at grafting. All grafts were well vascularized from the host iris. Grafts from younger donors contained several neurons typical of spinal cord including alpha-moto-neuron-type cells. Cells were found in clusters in gray matter areas surrounded by white matter. Extracellular recording revealed many spontaneously active cells. Several had high sustained discharge (10-25 Hz) and large amplitudes. Many cells could be excited by stimulation of the graft surface via activation of local afferents. It is concluded that the capacity of fetal spinal cord tissue to survive grafting to the eye chamber is inversely related to the donor age. Before E17, large grafts retaining several morphological and electrophysiological characteristics of spinal cord are obtained. The intraocular spinal cord graft provides a useful model for studies of spinal cord development and, using co-grafting techniques, a model for spinal cord regeneration and functional connectivity. PMID- 4043281 TI - Potent depressant effects of adenosine analogs on hippocampal slow-wave activity in the unanesthetized rat. AB - Adenosine and its analogs have previously been shown to exert a depressant effect on several measures of hippocampal excitability in the hippocampal slice and intact anesthetized preparation. In the present report, we examined the effects of intraventricular injections of adenosine analogs on hippocampal slow-wave activity in the freely moving rat. Each of three adenosine analogs-5'-N ethylcarboxamidoadenosine (NECA) and N6-(phenylisopropyl) adenosine (L- and D PIA)--were found to strongly suppress hippocampal electroencephalographic (EEG) activity. For instance, low doses of NECA (0.5 micrograms) produced an 80-90% decrease in the amplitude of the hippocampal EEG. NECA was approximately 20-fold more potent than L-PIA, and L-PIA was twice the potency of D-PIA. In separate experiments in the anesthetized rat, NECA and L-PIA were found to block completely the activation of the hippocampal theta rhythm elicited with brain stem stimulation. The effects of adenosine analogs on both the hippocampal EEG and theta rhythm were very effectively reversed with methylxanthine, 8-para sulphophenyl-theophylline (8-PSPT). The present findings demonstrate that adenosine analogs exert a powerful depressant effect on the hippocampal EEG in the natural unanesthetized state, and suggest that changes in the levels of endogenous adenosine may play a significant role in modulating the normal activity and function of the hippocampus. PMID- 4043282 TI - Regenerative potentials in rat neostriatal neurons in an in vitro slice preparation. AB - Regenerative potentials in rat neostriatal neurons were studied using the in vitro slice preparation. Some of the recorded neurons were intracellularly labeled with HRP. All had the morphological characteristics of the medium spiny neuron. Application of TTX (10(-5) g/ml) to the superfusing medium abolished fast action potentials generated by intracellularly injected depolarizing current. Application of TEA prolonged the spike duration by decreasing its repolarizing rate without affecting rising phase. After suppression of K-conductance by TEA, depolarizing current elicited both fast and slow all or none action potentials. Combined treatment with TTX and TEA revealed two types of depolarizing potentials, a slowly rising graded depolarizing potential and slow action potential. Substitution of Ca++ with Mg++ in the medium diminished the amplitude of these potentials. They were also blocked by application of Co++ into the superfusion medium. The duration of slow action potentials were increased with increase in the intensity of current pulse, with decrease in the resting membrane potential, and with increase in the concentration of TEA in the bathing medium. In the normal Ringer solution, local stimulation elicited depolarizing postsynaptic responses (DPSPs). Large DPSPs evoked by strong local stimulation triggered one or two fast action potentials. In some neurons, large DPSPs could trigger both fast and slow action potentials. They were consistently triggered after application of TEA (1 mM) to the medium. When a relatively high concentration of TEA (4 mM) was applied to the Ringer solution, locally evoked DPSPs could trigger only slow action potentials. In double stimulation experiments, a large reduction in the amplitude and the duration of test DPSPs was observed up to about 150 ms interstimulus interval. PMID- 4043283 TI - The pattern specificity of velocity aftereffects. AB - Interactions between two different visual patterns, a coarse grating and a fine texture pattern, were investigated in the context of velocity aftereffects in human subjects. The perceived velocity shift, in which the perceived velocity of a moving test pattern is reduced following exposure to a similarly moving adaptation pattern, is apparent when the adaptation and test patterns are of the same or different types. The aftereffect transfers interocularly in both cases. The directional tuning of the aftereffect is broad, and has a different profile for texture adaptation than for bar adaptation. When adaptation is to a composite stimulus comprising independently moving bars and texture, the aftereffect varies according to the nature of the test pattern. The results are discussed with reference to interactions between the responses of neurones in feline striate cortex to the two types of pattern. PMID- 4043284 TI - Developmental genetics of the retina: evidence that the pearl mutation in the mouse affects the time course of natural cell death in the ganglion cell layer. AB - The time course of natural cell death was studied postnatally in the ganglion cell and inner plexiform layers of the retina in the developing mouse. We examined congenic wild-type, albino and pearl mutants from birth to 12 days of age. In both wild-type and albino mice, natural cell death proceeded with an increasing rate from birth to a peak 6 days after birth, and with a decreasing rate thereafter. In contrast, cell death in pearl mutants proceeded with essentially a decreasing rate postnatally. The populations of neurones and glial cells in the ganglion cell and inner plexiform layers of the retina were also determined in adult mice. It was shown that pearl mutants had a slightly smaller number of cells in those layers than both wildtype and albino mice, and that the difference was probably due entirely to the numbers of neurones. We conclude that the pearl mutation in the mouse affects the timing of developmental cell death, but the effect is not directly related to the amount of pigment in the eye. PMID- 4043285 TI - Classical conditioning of the nictitating membrane response of the rabbit. I. Lesions of the cerebellar nuclei. AB - The classically conditioned nictitating membrane response (NMR) of the rabbit, a simple form of associative motor learning, is crucially dependent upon the cerebellum. Discrete unilateral lesions of the cerebellar nuclei were made in 20 rabbits. Lesions of the anterior interpositus nucleus (IA) abolished NMR conditioning to light and white noise stimuli on the side of the lesion without affecting unconditional responses. Lesions of the posterior interpositus nucleus, fastigial and dentate nuclei were without effect upon NMR conditioning. PMID- 4043286 TI - Classical conditioning of the nictitating membrane response of the rabbit. II. Lesions of the cerebellar cortex. AB - The nictitating membrane response (NMR) of 20 rabbits was conditioned to light and white noise conditional stimuli (CSs) using a periorbital shock unconditional stimulus (US). Unilateral lesions of the cerebellar cortex, sparing the underlying deep nuclei, were then made. Small lesions of cerebellar cortical lobule HVI abolished conditioning on the side of the lesion to both CSs leaving unconditional responses to the US intact. Larger lesions of the posterior lobe which spared HVI did not impair NMR conditioning. We conclude that cerebellar lobule HVI is essential for NMR conditioning in the rabbit. Degeneration following critical lesions of HVI was seen in a restricted region of the inferior olive - the medial part of the dorsal accessory olive and the adjoining medial part of the dorsal leaf of the principal olive. This region of the olive provides somatosensory information from the face to HVI. We suggest that HVI receives information related to the US via climbing fibres from the olive and CS information via mossy fibres from the pontine nuclei. The critical changes underlying NMR conditioning may be the association of these two inputs at the Purkinje cells of cortical lobule HVI. PMID- 4043287 TI - Respiratory roles of genioglossus, sternothyroid, and sternohyoid muscles during sleep. AB - We examined the respiratory activity of the genioglossus, sternothyroid, and sternohyoid muscles of the rat during nonrapid eye movement (non-REM) and REM sleep. Each animal carried implanted electrodes for recording the integrated EMG activity of respiratory muscles, the postural tone (EMG), and electrocortical activity (polygraphic identification of sleep-waking states). The three upper airway muscles exhibited inspiratory activity during non-REM sleep while rats breathed ambient air. Curled up postures promoted inspiratory activity of genioglossus and sternothyroid muscles, an effect enhanced by CO2 breathing but reduced by hypoxic breathing. During REM sleep, genioglossus and sternothyroid muscles lost their activity but the sternohyoid muscles retained their inspiratory activity. We conclude that the genioglossus and sternothyroid muscles contribute to upper airway patency during non-REM sleep, an effect CO2 augments but hypoxia reduces. The sternohyoid muscles have at least two functions during both sleep states: they contribute to maintenance of upper airway patency and to rib cage fixation, thereby optimizing the ventilatory action of the diaphragm. PMID- 4043288 TI - Trunk position sense in the frontal plane. AB - Twenty healthy volunteers (ages 18 to 25 years) were tested for their ability to sense the lateral position of the top of their thoracic spine. When moved slowly from side-to-side in the frontal plane with vision occluded and pelvis immobilized, they could sense the position of a midline point on the skin at the T1 level to within 3 mm of a mean center position in relaxed standing tests, and to within 9 mm in supine tests. When subjects centered themselves actively, or additionally, contracted trunk flexor or extensor muscles to predetermined levels of activity, no increase in trunk positioning accuracy was found. The effect of a lateral pelvic tilt or lateral trunk moment had little effect on trunk positioning accuracy, but always induced a characteristic trunk offset. No differences were found in any of these results between males or females, or gymnasts or nongymnasts. PMID- 4043289 TI - Relationship between interhemispheric nigrostriatal projections and the direction of rotational behavior induced by amphetamine. AB - This experiment dealth with the relationship between the direction of amphetamine induced turning and the distribution of crossed nigrostriatal projections in the rat. Animals that showed a high degree of asymmetry, as indicated by the consistency and amount of turning behavior elicited by repeated amphetamine administration, were implanted with horseradish peroxidase (HRP) in the striatum either ipsilateral or contralateral to their dominant direction of rotation. Microscopic analysis revealed a relationship between the direction of amphetamine induced asymmetry and the number of HRP-labeled cells found in the substantia nigra contralateral to the striatum into which the tracer was implanted; i.e., animals with the HRP applied contralateral to their dominant turning direction had more labeled cells in the caudal part of the substantia nigra of the opposite hemisphere than those animals implanted ipsilaterally. There was no relationship between the direction and the number of labeled cells found in the ventral tegmental area and retrorubral area contralateral to the tracer implantation site. Moreover, there was no association between the direction of amphetamine induced turning and the number of labeled cells found in the homolateral substantia nigra, or ventral tegmental and retrorubral areas. PMID- 4043290 TI - Cerebrospinal fluid pressure and resistance to absorption during development in normal and hydrocephalic mutant mice. AB - Hydrocephalic mutant mice and matched siblings at different ages were used to measure the pressure and the resistance to drainage of the cerebrospinal fluid (CSF) from the lateral ventricles and from the cisterna magna with glass micropipets. The resting CSF pressure in normal mice increased between 1 to 2 and 4 to 8 days after birth and subsequently decreased between 4 to 8 and 14 days after birth. In hydrocephalic mice the resting pressure was not significantly different from normal in the 1st week after birth, but by 14 days the pressure was significantly higher in hydrocephalic mice. For normal mice, the resistance from the lateral ventricles at 1 to 2 days after birth was 143.9 mm H2O min microliter-1 and it decreased rapidly to 62.0 at 4 to 8 days, and to 21.2 mm H2O min microliter-1 at 14 days. The resistance to absorption from the cisterna magna in normal mice declined from 94.9 to 44.4 and to 26.8 mm H2O min microliter-1 at 1 to 2 days, 4 to 8 days, and 14 days after birth, respectively, suggesting that the absorptive capacity of the subarachnoid outflow sites increased during that period. Thus resistance measured from the lateral ventricles was significantly higher than that from the cisterna magna in the 1st week after birth, suggesting that in immature mice there is a resistance to flow of CSF through the ventricular system. In hydrocephalic mice the resistance measured from the lateral ventricles was higher than for normal animals at 181.5, 106.4, and 103.7 mm H2O min microliter-1 for 1 to 2 days, 4 to 8 days, and 14 days, respectively. Resistance from the cisterna magna in hydrocephalic animals was not significantly different from normal at any age. Thus it is concluded that the hydrocephalus is associated with an obstruction to the flow of CSF from the ventricles. PMID- 4043291 TI - Respiratory inhibition induced by transient hypertension during sleep in unrestrained cats. AB - The effects of transient blood pressure elevation, induced by intravenous injection of phenylephrine, were studied in drug-free, unrestrained cats during sleep and waking. Transient hypertension evoked an increase in respiratory cycle duration (Ttot), an effect which was most prominent during quiet sleep. Transient hypertension evoked no overall change in inspiratory duration (Tdi) during any sleep-waking state, although reduction of diaphragmatic EMG amplitude was observed. Thus, the ratio of diaphragmatic activity time to total respiratory cycle duration (Tdi/Ttot) was decreased following blood pressure elevation. Apneic episodes occasionally occurred, and these occurrences were more frequent during sleep states. Apneas induced during quiet sleep were often associated with transient or sustained arousal. PMID- 4043292 TI - Effects of hypoxic-ischemic encephalopathies on kindling in the immature brain. AB - The effects of hypoxia and ischemia on subsequent kindling in the immature animal were assessed using three experimental designs. In the first experiment, 15- and 30-day-old rats were exposed to either 15 or 30 min of 6% oxygen and then subsequently kindled. In the second experiment, 15- and 30-day-old rats underwent unilateral carotid ligation followed by kindling in the ipsilateral amygdala. In the third experiment, the Levine procedure was used (unilateral carotid ligation followed by exposure to 6% oxygen) and rats were subsequently kindled in the amygdala either ipsilateral or contralateral to the side of the carotid ligation. Hypoxia and carotid ligation alone failed to result in any significant difference from controls in rate of kindling. In rats that underwent the Levine procedure and were kindled in the amygdala ipsilateral to the side of the carotid ligation, there was a marked inhibition of kindling. These results suggest that although mild hypoxia or ischemia did not alter seizure susceptibility, moderate to severe hypoxia-ischemia inhibited the development of generalized seizures. The mechanism of this inhibition is not known. PMID- 4043293 TI - Variable expression of intermediate filament proteins during embryonic development of human optic nerve. AB - The intermediate filament protein composition of human optic nerve and tract was analyzed by two-dimensional gel electrophoresis. Optic nerves were analyzed at 15, 19, 22, and 24 weeks of embryonic development and the results were compared with the composition of adult optic nerve. The optic tract was analyzed at the later stages of development. The proteins were visualized by Coomassie blue staining and immunoblotting with specific antibodies to glial fibrillary acidic protein (GFAP) and vimentin. The 70K and 150K neurofilament proteins were first observed at 24 weeks. At 15 weeks of development, only trace amounts of GFAP were observed and vimentin was the predominant intermediate filament protein. In contrast, there was more than twice as much GFAP as vimentin in the adult optic nerve. The results also showed that the ratio of GFAP to vimentin is higher in the optic tract than in the optic nerve during development, whereas in adult tissue, the ratio is the same for the two regions. In pathological situations with axonal dropout, a complete loss of neurofilament proteins was observed. The amounts of both GFAP and vimentin were the same for both the normal and involved optic nerve. These results are discussed in terms of the development of the optic nerve. PMID- 4043294 TI - Sources of the catecholaminergic innervation of the trigeminal nucleus caudalis in cat. AB - Injections of the retrogradely transported fluorescent dye, Evans blue, into the trigeminal nucleus caudalis were combined with the glyoxylic acid histofluorescence technique to determine the sources of catecholamine-containing varicosities innervating nucleus caudalis. Results indicate that the sources of this catecholamine innervation are widespread, originating from cell bodies throughout the brain stem including the medullary catecholamine cell groups as well as the noradrenergic nuclei of the dorsolateral pons, including locus ceruleus, subceruleus, Kolliker-Fuse, and the parabrachial nuclei. A small projection from the presumably dopaminergic neurons of the hypothalamus was also noted. The catecholamine innervation of n. caudalis in the cat is from widespread brain stem sources, a pattern different from the catecholamine innervation of the spinal cord, which receives its major catecholamine input from the Kolliker-Fuse nucleus. PMID- 4043295 TI - Behavior of single motor units of human tibialis anterior muscle during voluntary shortening contraction under constant load torque. AB - The recruitment and discharge frequency of motor units during voluntary shortening contraction with constant load torque were studied in tibialis anterior muscle of 10 human subjects trained to dorsiflex the tibiopedal joint as linearly as possible from 30 degrees plantar flexion from the neutral position (tibiopedal joint angle, 90 degrees) by 20 degrees in 1, 2, 3, 5, 8, and 10 s. A constant load torque of 0, 5, 10, 20, and 25% of maximum voluntary torque of the muscle was applied. When speed of shortening contraction was constant there was considerable degree of constancy in the muscle length at which individual motor units were recruited. However, the recruitment order was not rigidly fixed among the units whose length range of recruitment overlapped. When the contraction was performed faster the units were recruited earlier. The discharge frequencies of the motor units changed little with a given ramp shortening of the muscle. There were also few changes in frequency among different contraction speeds. With increasing load torque to the muscle, the discharge frequency increased slightly at a rate of 1 to 2 Hz by increase of the load. The results suggest that the speed of shortening was coded by recruitment of motor units and that discharge frequency did not play any major role when a muscle was shortened under constant load torque. PMID- 4043296 TI - Antinociceptive effect of intracisternal carbamazepine evidenced by the bradykinin-induced biting-like response in rats. AB - Intracisternal injections of carbamazepine produced a rapid and dose-dependent suppressive effect on the biting-like response induced by microapplication of bradykinin onto the tooth pulp (ED50: 2.62 micrograms/rat). Thus, the medullary dorsal horn is probably one of the primary sites for the antinociceptive activity of carbamazepine. PMID- 4043297 TI - Development of kindling: whole-brain stimulation in rats. AB - Previous studies have demonstrated that low-intensity electrical stimulation of some specific brain regions in several animal species leads to gradual changes in behavior, culminating in generalized seizures (kindling). We found that repeated whole-brain stimulation in rats with electrical currents of 5 and 3 mA elicited progressive behavioral changes and finally triggered convulsive seizures. PMID- 4043298 TI - Peroxidase activity at nodes of Ranvier in some commonly used laboratory animals after intramuscular administration of horseradish peroxidase. AB - During retrograde transport of intramuscularly administrated horseradish peroxidase (HRP) nodal axon segments of rabbit, rat, and mouse peripheral nerve fibers became HRP-positive and showed a striking proximodistal segregation of certain axoplasmic organelles. HRP-positive bodies and HRP-negative vesiculotubular membrane profiles were seen just distal and proximal to the nodal midlevel, respectively. This appearance was similar to that found earlier in HRP transporting feline muscle nerve fibers. Some mechanisms that might explain the segregated appearance are briefly discussed. PMID- 4043299 TI - GABA and phospholipids in penicillin-induced seizures. AB - The effect of a suspension of GABA and phosphatidylserine (PS), phosphatidylcholine, or phosphatidylethanolamine was studied on penicillin induced epileptic activity in rats. GABA-PS significantly reduced the number of spikes, in comparison with either the other phospholipid compounds or normal saline. No effect was observed after GABA or PS administration alone. We suggest that the different effects probably depend on extracellular and intracellular factors. PMID- 4043300 TI - Myotube clusters do not bear any quantitative relation to the extent of motoneuron survival. AB - We conducted a quantitative study of the trochlear motoneurons and the myotube clusters in the corresponding superior oblique muscle of the Japanese quail, before, during, and after the period of normally occurring motoneuron degeneration. A ratio of approximately 1:1 between myotube clusters and neurons was observed at the onset of motoneuron degeneration. The number of myotube clusters prior to neuron death was 37% greater than the number of neurons surviving after cell death. These results are in contradiction with the hypothesis that the number of myotube clusters is the deciding factor for the survival of motoneurons during the critical stages of development. PMID- 4043301 TI - Multiple sites of histamine storage in superior cervical ganglia. AB - Histamine and mast cells are present in substantial quantities in superior cervical ganglia (SCG) in a variety of animals. In this study, SCG from mast cell deficient W/Wv mice, from cogenic +/+ wild-type, and from Wistar control mice were examined for their endogenous histamine content and mast cell numbers. Measurements of SCG extracts with a micro-radioenzymatic histamine assay revealed that +/+ and Wistar ganglia contained about 20 pmol histamine per ganglion or 0.6 nmol/mg protein. Light microscopic inspection with toluidine blue staining of 6 micron sections prepared from +/+ and from Wistar SCG showed the presence of about 85 mast cells in each species. By contrast, no mast cell was observed in serial-sectioned SCG from W/Wv mice; despite the absence of stainable mast cells, their SCG consistently contained endogenous histamine, on average, 2 pmol per ganglion. These results are interpreted as evidence for the existence of a nonmast cell histamine compartment in sympathetic ganglia. PMID- 4043302 TI - Adrenocortical hormones and brain growth: reversibility and differential sensitivity during development. AB - The brain growth that follows adrenalectomy can be arrested by corticosterone replacement. Administered daily in combination with deoxycorticosterone, the brain and body conditions of intact rats are closely matched. Using this combination dose (corticosterone, 7.0 mg/kg; deoxycorticosterone, 1.0 mg/kg), hormonal replacement was systematically administered and withheld in a balanced design in order to assess the relative sensitivity of brain tissue to corticosteroids across time, and to determine if brain growth suppressed during one phase could recover upon hormone withdrawal during a second phase. Female forebrains were less sensitive to the hormones during an early phase which spanned ages 27 to 46 days. In contrast, 70 to 80% of potential growth was suppressed by replacement during a later period (ages 46 to 65 days). Brain size differences included weight and forebrain length, width, and depth. Hind brains were more sensitive to hormone replacement during phase 1. However, this suppressed growth was completely regained after hormone withdrawal during phase 2. On the other hand, growth that had occurred in the absence of adrenal steroids was not reversed, only arrested, by subsequent administration. We conclude that the rat brain became increasingly sensitive to the suppressive influence of adrenal steroids as females matured from juveniles to adults. Coupled with this sensitivity was the ability--apparently complete--to recover from steroid-induced brain growth suppression. PMID- 4043303 TI - Effect of cooling on force oscillations during maximal voluntary eccentric exercise. AB - The effect of superficial cooling on force oscillations during maximal eccentric exercises of the quadriceps femoris was studied in 10 adults. Maximal (i) shortening (concentric) and (ii) lengthening (eccentric) exercises were performed at a velocity of 120 degrees/s through 60 degrees of knee flexion while linear envelope EMG signals were recorded from the surface of the vastus medialis muscle. Force oscillations (12.4 +/- 2.8 Hz) were present in all subjects in the first series of eccentric exercises. After 30 min of cooling, the oscillations were eliminated in two subjects and were reduced in number in two others of the five subjects in the experimental group. In contrast, all subjects in the control group still had oscillations when retested after a 30-min rest period. During the eccentric exercises, a synchronous silent period in the EMG tracings was evident just before a decrease in force. Subsequently, the EMG activity resumed and the force increased (force oscillation). Because the force oscillations were of large amplitude and occurred only during eccentric exercise, we conclude that the force oscillations were similar to physiological action tremor. Because the force oscillations and EMG patterns were altered by cooling, the mechanisms that initiate such oscillations during maximal eccentric exercise are suspected to include a neural component. PMID- 4043305 TI - Intramuscular acupuncture-like electrical stimulation inhibits stretch reflexes in contralateral finger extensor muscles. AB - Electro-acupuncture is one of many physical measures used to relieve musculoskeletal pain and to improve the associated restricted range of motion. Experiments were designed to determine whether or not acupuncture-like stimulation inhibits stretch reflexes in an arm extensor muscle in human volunteers. Surface electromyographic recordings were made on the right extensor digitorum communis muscle and averaging techniques were used to study the reflex responses to brief deflection of the finger with a solenoid-driven probe. The ratio M1:M2 of two components of the reflex was reduced during continuous acupuncture-like stimulation of the contralateral first dorsal interosseus and extensor digitorum communis muscles near their motor points (acupuncture points LI 4 and LI 11). Concomitant changes in skin temperature were observed on the forehead and in the arm in which acupuncture-like stimulation was used. In control experiments, when the acupuncture needles were inserted subcutaneously and stimulated with the same current parameters at distinctly uncomfortable intensities, no change in the reflexes occurred. These findings show that acupuncture-like stimulation exerts physiologic effects on the central nervous system, mediated presumably by muscle afferent fibers. The effects may be relevant to relief of muscle spasm and musculoskeletal pain, and restoration of mobility. PMID- 4043304 TI - Effects of alcohol ingestion on zinc content of human and rat central nervous systems. AB - The abundance of zinc in hippocampal mossy fibers has stimulated investigation of zinc status in various pathologic states in which behavioral or anatomic deficits involving the hippocampus are known to occur. Limited autopsy studies of chronic alcoholic humans have suggested that the content of zinc might be reduced in several brain regions whereas reported attempts to replicate these findings in ethanol-exposed experimental animals have produced inconsistent results. In this comparative study, the zinc concentration in 10 brain regions, all spinal cord segments, and microdissected hippocampal subfields was measured by isotope ratio mass spectrometry. A widespread 15 to 20% reduction in zinc content was observed in all regions of chronic alcoholics compared with controls but a selective involvement of hippocampus was not detected. In the experimental studies, groups of rats were exposed to ethanol by one of three routes: inhalation for 2 weeks, as an ethanol/liquid diet for 3 months, or a single intoxicating i.p. dose. Determinations of tissue uptake of radiozinc and of total zinc content were made. In contrast to human pathologic material, zinc pool size and tissue uptakes were not affected by experimental ethanol administration by any route. This study confirmed that a reduction in zinc concentration occurs in the central nervous system of chronic alcoholics. The animal studies indicated, however, that simple ethanol exposure, even for prolonged periods, does not perturb zinc metabolism in brain. Together, these observations argue that the abnormalities of zinc metabolism in chronic alcoholics are possibly secondary to homeostatic alterations associated with hepatic failure. PMID- 4043306 TI - Atypical cilia in ciliated cysts of the parathyroid glands of dogs exposed to ozone. AB - This report deals with the occurrence of atypical cilia in ciliated cysts of parathyroid glands in dogs after exposure to ozone inhalation at 0.75 ppm close level for 48 h. Electron microscopic examination revealed cytoplasmic blebs with none, one, two ore more axial microtubule complexes (compound) surrounded by a single membrane and containing little or excessive matrix. Also seen where helicoidal cilia. The present anomalous behaviour of the cilia in the prevalent ciliated cysts in ozone treated dogs is consistent with the previously described effects of ozone inhalation on the parathyroid glands. PMID- 4043307 TI - Short term in vivo method for prediction of the fibrogenic effect of different mineral dusts. AB - The effect of intratracheal introduction of different metal and mineral dusts and the change in activity of pulmonary acidic phosphatase have been studied as a function of time (72 h, 2 weeks, 1, 12, 20 months). The activity and localization of acid phosphatase were compared with the degree of pulmonary damage caused by dusts. The degree of fibrosis was determined on the basis of the composition of cells and fibres, according to Belt and King's classification. Due to the membrane-damaging effect of DQ 12 silica and mixed dusts (enargite and porphyry rock dusts) an increase in acid phosphatase activity of macrophages could be observed at the end of the first month. At the same time non-fibrogenic or only mild fibrogenic dusts (bentonite, corundum, scarnic rock dust) caused a decrease or disappearance of tissue acid phosphatase activity. It has been stated that there is a very close correlation between the change in pulmonary acidic phosphatase activity and the progression of pulmonary fibrosis due to exposure to mineral dusts. The above investigations have been most useful in predicting the subsequent effect of rock patterns, emphasizing at the same time the importance of in vivo long term experiments. PMID- 4043308 TI - Effects of chloroquine on hepatocytic organelles in rat. AB - The administration of chloroquine (Resochin) in rats produces significant changes in the hepatocytic organelles, which are described by morphometric and biochemical methods. There is an increase in oxygen uptake by the isolated mitochondria together with an increase in the specific surface of cristae. Volume densities of mitochondria, lysosomes, rough and smooth endoplasmic reticulum and Golgi apparatus increase, while that of glycogen decreases. The affecting mechanisms are discussed. PMID- 4043309 TI - Skeletal muscle metabolism in mice bearing adenocarcinoma. II. Histochemical alterations in acid and alkaline phosphatases. AB - In Swiss albino mice bearing adenocarcinoma the degree of pathological damage as revealed by the activities of acid and alkaline phosphatases is greater in skeletal muscles closely proximal to the tumor site than in those away from it. Acid and alkaline phosphatases in myofibres of triceps, pectoralis and gastrocnemius muscles show a direct relationship between myofibre necrosis and activities of these phosphatases. PMID- 4043310 TI - Ischaemic contracture in isolated rat heart: reversible or irreversible myocardial injury? AB - An isolated rat heart preparation was reperfused at 37 degrees C for 10 min after 10, 20, 30 and 40 min of ischaemia. The left ventricular tension was measured by means of a balloon catheter filled with water and connected to a pressure recorder. The left ventricular resting tension began to increase at 9 +/- 1 min (mean +/- SEM) and was maximally developed (myocardial contracture) at 18 +/- 1 min of ischaemia. There was a striking and constant exacerbation of the resting tension during reperfusion after 30 and 40 min (but not after 10 or 20 min) of ischaemia with simultaneous acceleration of creatine phosphokinase (CK) release into the coronary effluent and with the loss of the recovery of contractile activity. Myocardial adenosine triphosphate (ATP)-content decreased during 20 min of ischaemia more in the endocardial (ENDO) (from 17.7 +/- 1.9 mumol/g to 0.7 +/- 0.1 mumol/g) than in epicardial (EPI) (from 15.5 +/- 0.9 mumol/g to 3.2 +/- 0.6 mumol/g) parts of myocardium. Reperfusion after 10 min of ischaemia resulted in a slight increase of myocardial ATP-content both in EPI (from 7.5 +/- 0.6 to 10.4 +/- 0.8 mumol/g, p less than 0.05) and ENDO (from 5.0 +/- 0.8 to 8.9 +/- 2.5 mumol/g, n.s.). Reperfusion after the completion of contracture (after 20 min) had no effect on myocardial ATP-content. The results indicate that there is a transmural ATP gradient in ischaemic isolated rat heart and that myocardial ATP net production during reperfusion (10 min) is prevented after the development of ischaemic contracture.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4043311 TI - The evolution of sex and the role of sex in evolution. PMID- 4043312 TI - Quantitative genetic models of sexual selection. AB - Quantitative genetic models of sexual selection have disproven some of the central tenets of both the handicap mechanism and the 'sexy son' hypothesis. These results suggest that the 'good genes' approach to sexual selection may generally lead to erroneous results. Runaway sexual selection seems possible under a wide variety of circumstances. Quantitative genetic models have revealed runaway processes for sexually selected attributes expressed in both sexes and for attributes of parental care. Furthermore, the runaway could occur simultaneously in a series of populations that straddle an environmental gradient. While the models support the feasibility of runaway processes, empirical studies are needed to evaluate whether runaways actually happen. Estimates of critical genetic parameters are particularly needed, as well as measures of natural and sexual selection acting on the same population. The models also show that sexual selection has tremendous potential to produce population differentiation, particularly in epigamic traits. Differentiation is promoted by indeterminancy of evolutionary outcome, transient differences among populations during the final slow approach to equilibrium, sampling drift among equilibrium populations, and the tendency of sexual selection to amplify geographic variation arising from spatial differences in natural selection. Recent work with two- and three-locus models of sexual selection has produced results that parallel the results of the polygenic models. Thus the feature of indeterminate equilibria (outcome dependent on initial conditions) is common to both types of model. PMID- 4043313 TI - Uninterrupted protein synthesis is essential for survival in the early stages of carbon tetrachloride-induced hepatocellular necrosis in the mouse. AB - The fatal syndrome produced by cycloheximide given 6 h after a hepatonecrogenic dose of CCl4 is due neither to direct toxic synergism between CCl4 and cycloheximide nor to transient sinusoidal thrombosis. It is suggested that survival in the presence of unknown factors released from dying liver cells requires uninterrupted protein synthesis. The life-saving effect of sterilization of the intestine by antibiotics indicates that the gut flora or its products play a vital role in pathogenesis. PMID- 4043314 TI - Hemodynamic studies in a parabiotic model of portal hypertension. AB - Splanchnic and systemic hemodynamic studies were performed in a rat model of parabiosis and portal hypertension. A portal hypertensive and a normal rat were surgically united side to side. A hyperdynamic circulation, characterized by increased cardiac index (413 +/- 26 vs 318 +/- 23 ml X min-1 X kg-1; p less than 0.05) and portal venous inflow (9.61 +/- 1.29 vs 6.33 +/- 0.36 ml X min-1 X 100 g b.wt-1; p less than 0.05), was found in all the portal hypertensive rats but not in the normal parabiotic partners. These results do not support the existence of a transferable humoral factor mediating the hyperdynamic circulatory state of chronic portal hypertension. PMID- 4043315 TI - Calcium accelerates cholesterol phase transitions in analog bile. AB - Analog bile supersaturated with cholesterol was constituted, filtered and divided into equal portions containing no calcium or calcium, 2.5-15 mM. Aliquots were removed over the next 48 h and filtrates analyzed for cholesterol, bile acid and lecithin. Calcium accelerated cholesterol loss from solution in a dose-related fashion. PMID- 4043316 TI - 5-(Hydroxyimino)-4-methoxy-2-(pivaloylimino)thiazolidine-3 -acetamide, a reduced nitroheterocyclic derivative with potent schistosomicidal properties. AB - The synthesis and antischistosome properties of 5-(hydroxyimino)-4-methoxy-2 (pivaloylimino)thiazolidine-3- acetamide (1) are described. The compound was prepared by reduction of the nitrothiazoline (2) with stannous chloride in methanol, and represents the first example of a reduced nitroheterocyclic compound showing potent schistosomicidal properties. The possible relationship of compounds such as 1 to the as yet unidentified reduced active but toxic entities formed in vivo from nitroheterocyclics like metronidazole is discussed. PMID- 4043317 TI - Serotonergic and cholinergic interaction in the regulation of pituitary-adrenal function in rats. AB - It has been proposed that the central serotonergic inputs which modulate pituitary-adrenal secretion are mediated by cholinergic neurons. We have tested this hypothesis in intact rats. Male Sprague-Dawley rats were injected with cholinergic and serotonergic agents which enhanced transmitter function and with receptor blocking agents. Agents were injected, singly and in combination, into both unstressed and stressed animals. Since the response to cholinergic agents might be due to changes to vasopressin release, Brattleboro (vasopressin deficient) rats were also injected with cholinergic agents. The level of plasma corticosterone at 1-h post-injection was determined. Results indicate that the serotonin receptor blockade decreased the stimulatory, cholinergic effect of physostigmine. Cholinergic receptor blockers did not significantly reduce the corticosterone rise induced by 5-hydroxytryptophan. These results do not support the hypothesis of cholinergic mediation of serotonergic input. Nicotinic and muscarinic receptors appeared to exert opposing influences on the system. The nicotinic receptor antagonist was able to block the stimulatory effect of physostigmine. The muscarinic receptor antagonist significantly elevated plasma corticosterone levels. No differences were found in the effect of physostigmine on Brattleboro rats as compared to controls. These data are interpreted as suggesting that 1) the acetylcholine-induced stimulation of pituitary-adrenal function is mediated, in part, by serotonergic neurons; and 2) stimulation of nicotinic receptors is facilitatory whereas stimulation of muscarinic receptors is inhibitory to pituitary-adrenal function. PMID- 4043318 TI - Effects of exchange transfusion with perfluorochemical emulsions on hepatic oxygen supply and blood flow in the rat. AB - Exchange-transfusion to hematocrit 20 with isotonic perfluorochemical (PFC) emulsions containing 3% hydroxyethylstarch (HES) in rats breathing 100% oxygen produced significant reductions of hepatic PO2 and blood flow in comparison to rats hemodiluted with isotonic 3% or 6% HES solution. The results indicate that PFC and/or emulsifiers were associated with adverse effects on liver blood supply. PMID- 4043319 TI - Role of peripheral chemoreceptors in response to smoke-induced apnea vs tracheal occlusion. AB - Reflex autonomic changes which occur after cigarette smoke enters the upper airways are partially due to peripheral chemoreceptor stimulation. Chemoreceptor denervation attenuates but does not abolish smoke induced bradycardia. Denervation nearly abolishes bradycardia induced by tracheal occlusion. Hypertension accompanies smoke induced apnea but does not occur during tracheal occlusion. PMID- 4043320 TI - Neuroma formation and abnormal afferent nerve discharges after partial beak amputation (beak trimming) in poultry. AB - Following partial amputation of the beak recordings were taken of the electrical activity from single afferent fibers of the intramandibular nerve. A total of 192 single afferent fiber units were isolated of which 47 were classified as nociceptors, with an abnormal pattern of discharge, and 89 were abnormal spontaneously active units. Following amputation neuromas were developing by 15 days after surgery and they were well formed by 20 to 30 days. The presence of neuromas together with abnormal spontaneous activity originating from them raise serious welfare questions concerning beak trimming. PMID- 4043321 TI - Axillary 5 alpha-androst-16-en-3-one in men and women: relationships with olfactory acuity to odorous 16-androstenes. AB - Axillary 5 alpha-androst-16-en-3-one (5 alpha-androstenone) levels were found to be significantly higher in men than in women but do not vary between left and right axillae, are not related to age, handedness or degree of hirsutism (in women) nor to anosmia to this steroid. In men (but not in women), levels are related linearly to axillary cholesterol concentrations but not to squalene. Olfactory thresholds for 5 alpha-androstenone varied widely, the lowest recorded being 0.2 ppb, but there was no difference in thresholds between men and women. Women (70%) found the smell 'repellant' but anosmia did not differ greatly between men and women (9-20%). Anosmia to the smell of 5 alpha-androst-16-en-3 alpha-ol was most marked in women (90%) rather than in men (45%). Axillary 5 alpha-androstenone values were generally consistent with the 'musky' or 'strong' smells of male axillary extracts, compared with the 'sweet' smell of those from female subjects. PMID- 4043322 TI - Bilateral lesions of suprachiasmatic nucleus eliminate circadian rhythms of oxygen consumption and the respiratory quotient in rats. AB - Bilateral lesions of the suprachiasmatic nucleus of the hypothalamus of rats abolished circadian rhythms of oxygen consumption and of the respiratory quotient (RQ). The RQ remained constant at a level intermediate between the maximum (about 1.0) and minimum (about 0.9) values in control animals. PMID- 4043323 TI - The effect of nicotine on ethanol-induced gastric ulcers in rats. AB - Nicotine, in concentrations of 5 and 25 micrograms/ml drinking water, given ad libitum for 10 days, dose-dependently increased lesion formation and worsened ethanol-induced ulceration in rat stomachs. Daily fluid intake and b.wt gain were not adversely affected by nicotine pretreatment. PMID- 4043324 TI - Age-dependent changes of rat liver plasma membrane composition. AB - The chemical composition of liver plasma membrane was studied in Wistar rats aged between 3 and 24 months. Results obtained indicate a significant age-dependent positive correlation of both the protein: phospholipid and cholesterol: phospholipid ratios, whereas the protein: cholesterol ratio seems to remain unaffected. Phospholipid analysis of liver plasma membrane reveals that only the phosphatidylcholine content has a significant negative correlation with age; all other phospholipid species remain basically unchanged. PMID- 4043325 TI - Spontaneous morphine withdrawal from the rat spinal cord. AB - A characteristic and reproducible sign of narcotic withdrawal is the naloxone induced increase in arterial pressure. In morphine-dependent rats allowed to undergo spontaneous withdrawal (6-24 h) and then transected at the spinal C-1 level, arterial pressure was maintained at a significantly higher level than either spinal-transected nondependent controls or morphine-dependent, spinal transected rats pithed from C-1 to L-4. These findings indicate that the morphine dependent spinal cord, independent of supraspinal influences, is able to exhibit an autonomic component of spontaneous withdrawal. PMID- 4043326 TI - Pharmacologic therapeutic window of pramiracetam demonstrated in behavior, EEG, and single neuron firing rates. AB - Following oral or intravenous administration, a representative cognition activator drug, pramiracetam sulfate, is shown to have a pharmacologic therapeutic window at three different levels of study: learned behavior, gross EEG activity of the frontal cortex and hippocampus, and firing rate of single hippocampal neurons. PMID- 4043327 TI - Nerve-mediated action of forskolin on guinea pig ileal mucosa. AB - The effects of forskolin on myenteric neuronal activity and mucosal function were examined in guinea pig ileum. Forskolin increased the excitability of myenteric neurons, and increased mucosal chloride secretion by stimulating enteric neurons as well as by acting directly on enterocytes. PMID- 4043328 TI - Role of inorganic phosphate in total biliary phosphorus determination. AB - Total phosphorus, inorganic phosphate, and phospholipids were measured in bile of rats and guinea pigs during choleresis and cholestasis produced by taurocholate and taurolithocholate, respectively. Under either experimental condition, total biliary phosphorus concentrations increased significantly in both species, due primarily to an increase in inorganic phosphate. These studies indicate that, if total phosphorus is taken as an estimate of biliary phospholipid concentration, correction for inorganic phosphate is essential under conditions associated with changes in bile secretory function. PMID- 4043329 TI - Antidiuretic hormone involvement in the release of alpha-melanocyte-stimulating hormone by hyperosmotic stimuli. AB - In the normal Wistar rat, the plasma alpha-MSH level was raised by hypertonic saline injection (as compared with control rats injected with isotonic saline). No such rise in alpha-MSH followed hypertonic saline administration in the Brattleboro (hereditary diabetes insipidus) animal (compared to isotonic saline injected controls). It is suggested that, in the rat, endogenous antidiuretic hormone is involved in the secretory response of the pars intermedia to osmotic stimuli. PMID- 4043330 TI - Differences in cardiac myosin light chain LC1 among human, monkey and sheep. AB - The atrial and ventricular myosin light chains of human, monkey and sheep hearts were compared by dodecylsulfate polyacrylamide gel electrophoresis. The atrial light chain 2 and ventricular light chain 2 are similar among these mammals. However, the atrial light chain 1 of monkey has different electrophoretic mobility from those of human and sheep. The monkey ventricular light chain 1 has same mobility as that of sheep but different from that of human. PMID- 4043331 TI - A method for karyotyping mouse blastocyst embryos developing from in vivo and in vitro fertilized eggs. AB - A method for karyotyping blastocyst-staged mouse embryos is described. The use of this protocol results in the recovery of a high percentage (greater than 70%) of readable karyotypes and can be completed rapidly. PMID- 4043332 TI - Incorporation of 32P into renal phospholipids of mice during postnatal growth. AB - During the first 40 days of life the rate of incorporation of 32P into total phospholipids and into phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, sphingomyelin, diphosphatidylglycerol, phosphatidic acid and phosphatidylinositol of mouse kidney was by some 25-35% higher than in older animals. Results suggest a different involvement of cellular membranes during of normal and compensatory renal growth. PMID- 4043333 TI - Possible involvement of calmodulin in apical constriction of neuroepithelial cells and elevation of neural folds in the chick. AB - Chlorpromazine and trifluoperazine HCl, antipsychotic drugs known to bind to calmodulin, reversibly inhibited elevation of neural folds by interfering with the contractile activity of apical microfilament bundles in developing chick neuroepithelial cells. PMID- 4043334 TI - Fecundity and longevity of houseflies after space flight. AB - After 7 days of space flight house flies, Musca domestica, exhibited similar longevity, but a reduction in reproductive output as compared to earthbound controls. This reduction was not observed in later generations. These data suggest that space flight directly alters the rate of ovarian development, but that this effect is not genetically transmitted. PMID- 4043335 TI - Immunological systematics of the extinct quagga (Equidae). AB - It has been debated whether the extinct quagga was a distinct fourth species of African zebra or whether it was merely the southern variant of the Plains zebra (Equus burchelli). Using a radioimmunoassay (RIA) technique, we have shown that proteins remaining in quagga skins from museums are much more similar to serum proteins of the Plains zebra than to those of the other two extant zebras. PMID- 4043336 TI - Isolation and characterization of hemagglutinins from the sponge Dysidea herbacea. AB - The sponge Dysidea herbacea (Keller) was found to possess hemagglutinins. The major component, DHA-I, is a protein with a mol. wt of 26,000, which dissociates into subunits of equal size (14,000). It contains large amounts of glutamic acid and aspartic acid residues, but no half-cystine, methionine or histidine residues. DHA-I reacted with rabbit and human AB0 erythrocytes. D-galactose and lactose were effective inhibitors of DHA-I. The sponge also contained a minor component(s) which reacted preferentially with rabbit erythrocytes but not with human AB0 erythrocytes. PMID- 4043337 TI - A simplified method for isocratic HPLC analysis of polyamines. AB - A simple technique is described for the separation and analysis of polyamines in tissues and body fluids, utilizing precolumn clean-up on disposable CM-cellulose columns, followed by an automatable HPLC procedure. Complete separation and analysis takes 12-15 min per sample with sensitivity in the pmole range. PMID- 4043338 TI - Connective tissue proteins on the injured endothelium of the rat aorta. AB - Type V collagen (TVC), fibronectin (FN), and laminin (LAM) were detected on the endothelial surface of mechanically injured rat aortas with the help of monospecific antisera and protein A - gold conjugates, carbon film surface replicas, and conventional embedding techniques. Deendothelialized tracks were produced in the thoracic aorta, and the presence of the connective tissue proteins on the luminal surface of the endothelium was studied. The changes in the distribution of the proteins during repair of the endothelial surface was followed for up to 6 days after injury. From 1 to 3 days after injury small numbers of gold particles, indicating the presence of TVC, were found between the adherent platelets on the freshly deendothelialized subendothelial matrix and in higher amounts on cell debris and collagen fibers. On the sixth day after injury, however, the amount of TVC between the sparsely distributed platelets on the deendothelialized areas was significantly higher than it was previously. FN and LAM were readily detectable on the subendothelial matrix and on the damaged marginal endothelial cells. These proteins were especially obvious on both margins of the tracks even from the first day after treatment. FN was found also in connection with fibrin precipitations as well as on the surface of some platelets and monocytes. The amount of FN and LAM present on the damaged area decreased slightly up to the sixth day. Monocytes and leukocytes adhered mostly at the margin of the wound area in the vicinity of the lesions on the endothelium. FN and LAM were often detectable under and around these adherent cells. Little of the connective tissue proteins was found on the uninjured and on the regenerated endothelial cells. The results showed subtle transitory changes in the surface pattern of the subendothelial connective tissue matrix of the injured intima. The adhesion of blood-borne cells may have been induced by FN and LAM on the endothelial surface near the lesions, and later partly prevented by increasing amounts of TVC on the surface. PMID- 4043339 TI - Lipids in cells of atherosclerotic and uninvolved human aorta. II. Lipid metabolism in primary culture. AB - [3H]Acetate and [3H]oleate were used to evaluate the rate of lipid synthesis in smooth muscle cells of human aorta. Experiments were carried out in primary cultures derived from the intima and media of unaffected and atherosclerotic vascular segments. The obtained results indicate that the rate of lipid synthesis in cells cultured from fatty streaks, atherosclerotic plaques, and underlying media is higher than in cells cultured from an uninvolved intima and media, respectively. The highest level of the label incorporation was observed in the fraction of phospholipids. In cultures obtained from fatty streaks and plaques, an increased incorporation of the labeled precursors into phospholipids, triglycerides, free sterols, and sterol esters was registered. The highest relative increase occurred in the fraction of sterol esters, the rate of acetate inclusion being five- to sixfold higher compared to the cell cultures derived from unaffected aortic segments. A direct and very close correlation was found between the rate of lipid synthesis and lipid levels in cells of normal and atherosclerotic aorta. The role of intracellular lipid metabolism disorders in the accumulation of excessive fat by "atherosclerotic" cells is discussed in this report. PMID- 4043340 TI - Copper toxicosis and tolerance in the rat. III. Intracellular localization of copper in the liver and kidney. AB - Male rats fed a 3 g/kg copper diet were killed sequentially up to 14 weeks. Copper in liver and kidney cortex was identified histochemically and assayed in homogenates and gradient fractions following analytical subcellular fractionation on reorientating sucrose density gradients. Copper accumulated fastest in the liver postnuclear (PNS) supernatant fraction which became saturated at 2 weeks; there was a distinct localization of copper in hepatic lysosomes which displayed progressively enhanced fragility. Rapid accumulation of copper then occurred in liver and kidney nuclear (N) fractions, peak copper concentrations coinciding with hepatic and renal tubular necrosis. Copper accumulated slowly up to 4 weeks and was maintained to 14 weeks in the cytosol of the proximal renal tubules from which it appeared to be excreted. Subsequently liver copper declined in both liver fractions and kidney (N) fractions; hepatic lysosomes regained stability, regeneration of liver and kidney occurred, and the rats were tolerant to continued copper administration. These findings do not support a primary role for copper-loaded lysosomes in the genesis of cell injury, but suggest that nuclear saturation may be the destabilizing event. Recovery is associated with changes in the subcellular distribution of copper within liver and kidney and renal excretion of excess. PMID- 4043341 TI - X-ray microanalysis of mineralized matrix vesicles of experimental saccular aneurysms. AB - An energy dispersive X-ray microanalytical study was designed to examine the mineral deposits in matrix vesicles found in the walls of experimental aneurysms from two rabbits (103 and 1071 days postoperatively) and two sheep aneurysms (234 and 1202 days postoperatively). The freeze-substitution technique was adopted for use to retain inorganic ions in situ. Numerous, various sized extracellular electron-dense structures, believed to be matrix vesicles were observed. Size histograms for the mineralized vesicles showed that the proportion of smaller vesicles was higher in the older animals. A total of 370 vesicles were analyzed. Calcium and phosphorus with small amounts of magnesium were identified. No particular calcium phosphate mineral was dominant with the mean Ca/P molar ratio for all animals falling in the 1.1-1.2 range. Correlation coefficients for interrelationships between calcium, phosphorus, magnesium, and size were weak except for calcium vs phosphorus which was close to one, consistent with some type of calcium phosphate being the major constituent of the mineralized vesicles. Smaller electron-dense particles, probably mitochondrial granules were seen in some smooth muscle cells; a small number were analyzed and contained calcium and phosphorus (mean Ca/P molar ratio of 0.86) but no magnesium. PMID- 4043342 TI - Effect of aging on human aortic protein composition. I. One-dimensional polyacrylamide gel electrophoretic analysis of tissue extracts. AB - Proteins extracted from matching areas of homogenized intimas of 17 human aortas, from two age groups (15-34 and 35-82), were studied after separation by polyacrylamide gel electrophoresis, silver staining, and densitometric scanning. Several definite protein bands including 6 major and 16 minor bands were identified in 17 aortic intima samples grossly and microscopically lesion free. However, such electrophoretic patterns were found to differ in the two age groups studied. For instance, (1) the integrated densities (amounts) of protein bands 1, 6, 13, 16, and 19 which we interpreted as of mural vascular origin were significantly higher in the younger age group, whereas the amounts of bands 2, 7, 9, 11, and 21 suspected to be of plasma origin were found to be significantly higher in the older age group; (2) protein band No. 8 was found to be double in the younger age group vs a single line in the older age group, whereas band No. 12 was the opposite. These changes in protein composition appear to correlate closely with diffuse intimal thickening found histologically in older age group, and will be further studied to relate to those in atherosclerotic lesions. PMID- 4043343 TI - Mitochondrial injury of pulmonary alveolar epithelial cells in acute paraquat intoxication. AB - The primary ultrastructural changes in pulmonary alveolar epithelial cells are described in paraquat-injected rats. Within 6-12 hr a single intravenous injection of 40 mg/kg paraquat dichloride caused selective mitochondrial swelling and loss of intramitochondrial granules within 24 hr in alveolar Type II cells. As the mitochondrial injury advanced, microvilli disappeared from apical plasma membrane followed by a cell destruction and detachment from basement membrane. This was accompanied by secondary damage to Type II cells and interstitial cells. These results indicate that paraquat may affect primarily the Type II cells and the first lesion produced occurs in mitochondria. PMID- 4043345 TI - Effect of dietary restriction on cholesterol biosynthesis in the liver and the intestine of cholesterol-fed rabbits. AB - The effect of dietary restriction (half of the control ration) on cholesterol biosynthesis was investigated in rabbits fed either standard or cholesterol-rich diets. Accompanying the amplification of hypercholesterolemia, additional disturbances of cholesterol metabolism were observed when cholesterol feeding was associated with dietary restriction. In the intestine, underfed rabbits showed a more marked inhibition of duodenal cholesterol biosynthesis from [14C]acetate following cholesterol feeding than rabbits on normal caloric ration. In contrast liver cholesterogenesis was equally suppressed in both groups receiving cholesterol-rich diets. Cholesterol biosynthesis from [14C]mevalonate was also inhibited by cholesterol feeding particularly in the duodenum of underfed rabbits. In addition cholesterol feeding induced a marked increase of the labeled esterified: free cholesterol ratio in the liver, demonstrating intensive esterification, this was enhanced by dietary restriction. The additional cholesterol which accumulates in the plasma and in various tissues in underfed rabbits is of dietary origin since the feedback control of cholesterogenesis by exogenous cholesterol was shown to be very effective in these animals. PMID- 4043344 TI - Solubility of tissue hydroxyproline in experimental intestinal anastomoses. AB - Salt and acid solubility of collagen are thought to reflect its degree of crosslinking. In order to examine postoperative changes in crosslinking of intestinal collagen, which are of importance to the stability of the intestinal wall, we have investigated the solubility of hydroxyproline in rabbit ileum and colon, both in unwounded intestine and after construction of an anastomosis. Solubility in salt and dilute acid was increased by a sonication procedure. This way, 9% of total hydroxyproline in the unwounded colonic wall was salt soluble and 65% acid soluble. A similar distribution was observed in ileum. Three days after operation the salt-soluble fraction was significantly elevated in samples from the anastomotic area. In colon, this increase also persisted 7 days postoperatively. Comparison of anastomotic samples collected 3 and 7 days after surgery shows a significant decrease in the acid-soluble and a significant increase in the solid fraction. This phenomenon occurs both in ileum and colon. These results indicate that during the first days after operation the integrity of the intestinal wall is weakened not only by a loss of collagen, but also by a changed solubility of the remaining collagen. PMID- 4043346 TI - Prognosis and diagnosis of Reye syndrome by discriminant analysis. AB - Discriminant analysis was used to discriminate between Reye syndrome (RS) patients and non-RS cases based either on conventional blood chemistry data obtained upon admission, or on the activities of hepatic mitochondrial enzymes in biopsy or necropsy tissue. The control group for blood chemistry measurements contained children with upper respiratory tract infections, varicella, etc. who did not develop RS, as well as healthy children. Subjects with no liver disorder (e.g., accidental death, sudden infant death, etc.) or with non-RS liver disorders were used as controls for hepatic enzyme studies. Hepatic damage indicators (aspartate aminotransferase, AST; alanine aminotransferase, ALT; and bilirubin) correctly classified 86-96% of non-RS cases and 61-71% of RS. By contrast, AST and ALT had little prognostic value (63% overall correct). Ammonia effectively classified favorable outcome cases (95% correct) but not unfavorable (14% correct). However, when ammonia was included with stage of coma information 88% of the favorable and 85% of the unfavorable outcome cases were correctly classified. Discriminant analysis of hepatic enzymes (glutamate dehydrogenase and monoamine oxidase activity) for a RS and a non-RS group correctly classified 80% of non-RS and 95% of RS specimens. The function was suitable for the direct evaluation of RS-like mitochondrial enzyme changes in rat liver. PMID- 4043347 TI - Nerve growth factor accelerates the early cellular events associated with wound healing. AB - The effects of injecting nerve growth factor (NGF) into subdermal air sacs on the backs of mice was studied. Sequential infiltration of cells into the lining of the sacs was observed. The initial cell type to infiltrate was the polymorphonuclear leukocyte, followed by highly vacuolated mononuclear cells, and then by fibroblast-like cells. This resembles the classical pattern of cellular responses during the normal process of wound healing. The kinetics for the peak accumulation of each cell type were dependent upon the concentration of NGF injected, and significant acceleration of infiltration of each cell type was observed with as little as 1 nM NGF. A similar acceleration of cellular infiltration was observed when mice were injected with the synthetic chemotactic peptide n-formyl-methionyl-leucyl-phenylalanine. This finding suggests that application of any chemotactic factor to wound sites may lead to accelerated tissue repair and an enhanced rate of wound contraction. The observation that NGF can act as a chemotactic factor in vivo may explain its ability to accelerate the healing of experimentally induced wounds in mice. PMID- 4043348 TI - Feed-forward: future questions, future maps. AB - "Feed-forward" is a technique that encourages families to imagine the pattern of their relationships at some future point in time. Questions about the future, in conjunction with positive connotation, put families in a metaposition to their own dilemmas and thus facilitate change by opening up new solutions for old problems. PMID- 4043349 TI - Our personal and professional lives: learning positive connotation and circular questioning. AB - The work of the Center for the Study of the Family in Milan has had wide influence. We describe its influence on us--the positive connotation of many car journeys, our self-training, and changes in how we view, and function in, our personal and professional lives. PMID- 4043350 TI - The negotiation of values in therapy. AB - Values are integral to all social systemic operations and therefore to the heart of the therapeutic process. For the therapist, values are an essential component in defining and assessing a problem, determining goals, and selecting therapeutic strategy. Therapists do not have a choice about whether they need to deal with values in therapy, only about how well. The training of therapists about their values needs to be integrated with the training about their own emotional and family issues. This training should be carried out in the context of treating families and have as its primary focus the relationship of the therapists' personal issues to the conduct of their therapy with families. Personal insight and mastery over handling their own values and family issues will maximize therapeutic effectiveness. PMID- 4043351 TI - On the boundary: family therapy in a long-term inpatient setting. AB - The paradigm for inpatient family therapy presented here is intended both as a description of, and a means of thinking about, family therapy in a long-term inpatient setting. It is meant to contribute to a delineation of treatment goals and strategies within a conceptual framework that is rooted in and expresses the complex clinical realities of inpatient treatment, where the locus of family therapy is the family-hospital boundary. The four functions described here are hierarchical in their relationships to each other, each function emerging only in the context of the logically prior function. Although, clearly, inpatient family therapy moves through stages parallel to those of other treatment modalities (14), the purpose of this paper is to explore therapeutic functions rather than present a prescriptive, linear description of successive phases of treatment. Joining, once achieved, cannot be left behind: it needs constant attending to, though more so at some times than others. Similarly with the other functions. It is helpful when pausing to examine one's work to note those functions that, at any given time, seem to be most at issue. For instance, the family of a patient well along the road toward discharge may promote a crisis (e.g., another family member may become symptomatic, the parents' marriage might suddenly seem in danger of falling apart, or the whole thrust of the treatment may be rejected peremptorily). On such occasions the inpatient family therapist must look for precipitating factors, not just in the domain of the family and its functioning and not just in his or her relationship with the family, but also in the context of the family's relationship to the hospital. Is the hospital riding roughshod over the family's feelings? Has important information from the family been ignored? Or, has important information been neglectfully withheld from the family? Is the treatment team moving too quickly toward discharge? Are staff, then, subtly pulling back from the patient or other family members as a way of coping with their feelings of loss? Have staff somehow communicated disappointment or pessimism or despair to the family? Has the family therapist somehow inadequately represented the family's needs to the treatment team or floor staff? Do treatment decisions therefore strike the family as insensitive or thoughtless? Has the family therapist been unable to frame treatment decisions in a way the family can accept and use constructively? PMID- 4043352 TI - A beginner's guide to the problem-oriented first family interview. AB - The large volume and diversity of family therapy resources can often confuse trainees who are in need of more abbreviated guidelines for managing their clinical responsibilities. This paper presents a structured outline of a problem oriented first family interview for the family therapy supervisor and the beginning family therapist. We view the first interview as an integrated process including the important tasks preceding and following the initial family meeting. After the goals that shape the work of the first interview are described, a step by-step guide to the twelve phases of the interview is presented: telephoning; forming hypotheses; the greeting; the social phase; identifying the problem; observing family patterns; defining goals; contracting; checklist; revising hypotheses; contacting the referral person; and gathering records. This approach to the first interview integrates a variety of structural and strategic procedures. The guide, intended for use in conjunction with close supervision, may serve as a foundation on which beginning therapists can build their unique styles. PMID- 4043353 TI - Stability/instability in the alcoholic marriage: the interrelationships between course of alcoholism, family process, and marital outcome. AB - Thirty-one alcoholic families who were originally studied in home, multiple family group, and laboratory settings were reassessed two years later to determine course of alcoholism and degree of marital stability. This paper presents data comparing baseline alcohol consumption and family interactional behavior at home with subsequent alcoholism and marital stability outcomes. Findings suggest that the relative degree of stability/instability in these marriages is best understood as a function of the "goodness-of-fit" between the relative predictability of drinking on the part of the identified alcoholic and the family's characteristic pattern of interactional behavior at home. PMID- 4043354 TI - The Beavers-Timberlawn model of family competence and the circumplex model of family adaptability and cohesion: separate, but equal? AB - An empirical examination of the association between instruments measuring the Beavers-Timberlawn Model of family competence and the Circumplex Model of adaptability and cohesion is presented. Even when triangulated measures were utilized to control for the divergent methods of data collection traditionally employed to operationalize these models of family health, family competence as measured by the Beavers-Timberlawn Family Evaluation Scales was either minimally (mothers) or not associated at all (fathers and children) with balanced and thereby optimal dimensions of adaptability and cohesion as measured by the Family Adaptability and Cohesion Evaluation Scales. Methodological and substantive explanations for the surprising lack of association between measures of these two prominent family assessment models are explored and short- and long-range implications for the growth and practice of family therapy are discussed. PMID- 4043355 TI - The missing triad: the case of two-child families. AB - Families, as they grow, become more complex in their psychosocial development. They also become more complex in their dyadic/triadic structure through the simple addition of another child. This article traces some of the structural changes that families undergo with the entry of each new child. It also raises several questions about how these very structures may, in turn, influence development of the children. By comparing two- and three-children families with different dyadic/triadic structures, these questions offer some basis for possible future research, as well as some speculation for the clinician. PMID- 4043356 TI - Sibling deidentification in the clinic: devil vs. angel. AB - A four-member family structure consisting of two siblings contrasting in personality (sibling deidentification) and each identified with a different parent (split-parent identification) was recently reported (15). In well functioning families, this tetrad or quadrangle is wide-spread in the first pair of siblings in the family and tends to be more common in same-sex pairs, suggesting that sibling deidentification is designed to mitigate the relatively intense sibling rivalry characteristic of these pairs and hence to maintain family harmony. In this collated case report, deidentification is found to follow the same pattern in 39 clinic first pairs. However, contrasting attributes are varied and nonevaluative in nonclinic pairs but mainly "good-bad" in clinic pairs, with polarization extreme. Results suggest that nonclinic siblings negotiate their identity (being) much as they negotiate about possessions (having) and that negotiations are blocked in clinic pairs, freezing mythic devil or angel identity. Intervention is directed at dislodging this block. PMID- 4043357 TI - [Morphobiophysical parallels in assessing the hepatotropic action of nitrosodimethylamine]. AB - On the third day after a single administration of nitrosodimethylamine (30 mg/kg) to white rats histochemistry reveals the greatest injury to the liver parenchyma. This correlates with a reduction in relative strength of intercellular contacts, an increase in relative strength of the membranes, and an elevation of the membrane potential during liver tissue survival in vitro. The latter fact can be explained, at any rate partially, by the lowering of the activity of cytoplasmic ATPase which competes with electrogenic Na+. K+-ATPase for ATP. PMID- 4043358 TI - [Effect of etatsizin on blood coagulability and the anticoagulant effect of heparin]. AB - Etacyzine, a new antiarrhythmic drug of the phenothiazine series, injected intravenously (1 mg/kg) does not change the blood coagulation balance of rabbits. The effect of heparin (100 Units/kg i.v.) reduces after preinjection of etacyzine (1 mg/kg). Etacyzine lowers the concentration of heparin in an aqueous medium and blood plasma. PMID- 4043359 TI - [Anticonvulsive activity of anticonvulsants and tranquilizers when used together]. AB - Experiments on mice were made to study anticonvulsive activity of the combinations of 5 tranquilizers (diazepam, chlorodiazepoxide, meprotan, trioxazin, mebicar) and 7 anticonvulsants (phenobarbital, hexamidine, benzonal, diphenin, chloracon, trimetin, carbamazepin) according to the maximal electroshock test. The data obtained form an experimental basis for the combined use of some anticonvulsants and tranquilizers in the treatment of epilepsy, since in a number of cases these combinations permit a significant lowering of the doses of both components without reducing their anticonvulsant activity. PMID- 4043360 TI - [Midantan activation of memory trace retrieval in rats]. AB - The authors studied the action of amantadine in recovery processes of the memory in some types of retrieval impairment: normal forgetting, "psychogenous" amnesia and latent inhibition. Antraperitoneal injection of amantadine (25 mg/kg) to rats I h before testing the preservation of the conditioned passive avoidance reaction was discovered to restore the conditioned reaction which went out as a result of long-term preservation. To restore the memory in amnesia and latent inhibition, 50 mg/kg amantadine was required. Thus, it has been shown that amantadine has reactivating properties in memory processes. PMID- 4043361 TI - [Effect of diazepam on interference processes]. AB - It has been found in experimental behavioral interference during training in two conditioned reflexes, rapidly following each other, that intraperitoneal injection of diazepam (2 mg/kg) 30 min before training potentiates the inhibitory effect of the defensive reaction to the drinking one. Electrophysiological analysis of the modulating effect of amygdaloid stimulation on the peripheral signal transmission via the central gray matter has demonstrated that in the majority of the neurons, diazepam produced a longer and pronounced inhibition of the excitatory reactions in response to electrocutaneous stimulation after conditioning stimulation of the amygdaloid. The data obtained allow an assumption that inhibitory processes determined by the activity of the GABAergic amygdalofugal system underlie the interference interrelations. PMID- 4043362 TI - [Effects of piracetam during prolonged use in an experiment]. AB - The spectrum of the pharmacological activity of piracetam administered for a long time was studied in experiments on mice and rats. It was established that administration of piracetam (300-400 mg/kg i. p.) for 10-42 days brought about potentiation of its antiamnestic effect, retardation of the processes of extinction, an increase in the emotional responsiveness, and preservation of the tranquilizing effect with no side effects (sedative or myorelaxant). The characteristic feature of piracetam effect on the extinction is its ability to decelerate this process only after its prolonged administration. It is assumed that under prolonged administration of piracetam there takes place the formation of a new functional system ensuring the memory trace stabilization. PMID- 4043363 TI - [Characteristics of the effect of psychotropic preparations on the synaptosomal uptake of monoamines]. AB - The authors investigated the ability of psychotropic drugs of different classes (psychostimulants, antidepressants and tranquilizers) to inhibit the reverse synaptosomal uptake of monoamine neurotransmitters in the rat brain. The psychostimulants amphetamine and cocaine (50 microM) powerfully suppressed noradrenaline, dopamine and serotonin transport without influencing GABA uptake. Phenazepam (50 microM) negligibly decreased the reverse synaptosomal uptake chiefly of noradrenaline. Studies of the antidepressants evidenced that inkazan is a highly selective inhibitor of the reverse uptake of serotonin, whereas other antidepressants such as zimelidine, imipramine and norzimelidine were discovered to inhibit the uptake of serotonin to a larger extent than that of other transmitters. The antidepressants pyrazidol and viloxazine turned out to be non selective inhibitors of the transport of all monoamines tested. Iproniazide and moclobamide appeared inactive as regards the reverse uptake of monoamine neurotransmitters. PMID- 4043364 TI - [Differences and similarity in the interaction of fenibut, baclofen and diazepam with phenylethylamine]. AB - The derivatives of GABA and beta-phenylethylamine (PEA) the tranquilizer phenibut and muscle relaxant baclofen (p-chloro-beta-phenyl-GABA, lioresal) diminished all studied effect of PEA in mice, namely seizures, sedation, excitation, hyperthermia. Diazepam diminished only seizures whereas haloperidol excitation and hyperthermia. PEA injections anatogonized (the sedative and hypothermic effects of phenibut and diazepam and the anticonvulsant (against l-kynurenine) effect of phenibut and baclofen. The role of antagonism to PEA in the mechanism of the antianxiety effect of tranquilizers is discussed. PMID- 4043365 TI - [Nonopiate subarachnoid analgesia induced by GABA-positive substances]. AB - It has been shown in experiments on rats exposed to a gradually increasing nociceptive action that subarachnoidal injection of GABA and its agonists (CHBA) isoguvacin, phenibut) in a dose of 0.6 mg causes an elevation of the thresholds of motor and, to a less degree, of emotional behavioral component of the painful reaction. Analgesia is potentiated by simultaneous subarachnoidal injection of inactive doses of chlorodiazepoxide. The GABA uptake inhibitor guvacin potentiates the effect of isoguvacin. The GABA-and phenibut-induced analgesia is not abolished by nalozone (0.04 mg subarachnoidally). PMID- 4043366 TI - [Changes in stimulation analgesia during chronic morphine administration]. AB - It has been shown in rat experiments that repeated administration of morphine produces tolerance to the effect of stimulation analgesia (SA). In the control group, the same stimulation of the periaqueductal gray matter (PGM) failed to produce tolerance. Naloxone (2 mg/kg i.p.) exerted a partially antagonistic influence on SA in the control group and did not affect the antinociceptive action of PGM stimulation in morphine-treated animals. PMID- 4043367 TI - [Utilization of the pharmacokinetic parameters of acetylsalicylic acid for optimizing its use with people of different ages]. AB - Nomograms for application of acetylsalicylic acid in persons of different age are presented. The nomograms are based on pharmacokinetic parameters of acetylsalicylic acid with regard to the age. Proceeding from the known constants of absorption and elimination, the nomograms are made use of to screen the loading and maintenance doses, to determine the time of administering the first maintenance dose and the maximal amount of the drug in the body, which was built up as a result of the use of the accepted treatment schedule. While using the nomograms one should be guided by the known therapeutic dose and the dosage intervals or by the therapeutic or maximal allowable dose. The nomograms are unsophisticated, fairly convenient, and help determine the optimal regimen of the use of acetylsalicylic acid in persons of different age. PMID- 4043368 TI - [Radiochromatographic study of the distribution of sidnocarb-14C and its metabolites in inbred mice]. AB - The title study permitted detecting genetic differences in sydnocarb metabolism. It was established that the rate of sydnocarb oxidation in BALB/c mice was higher than in C57B1/6 mice. PMID- 4043369 TI - [Possibilities for the strophanthin pharmacological correction of cardio- and hemodynamic disorders in dogs in the early stage of experimental lung-heart failure]. AB - Experiments on intact dogs and animals with an early stage of experimental cardiopulmonary insufficiency due to chronic pneumonia were made to study the action of strophanthine on the hemodynamics of the left and right ventricles and pressure in the pulmonary artery. Administration of the glycoside to animals with cardiopulmonary insufficiency increased the contractility of the right ventricle and the intensity of diastolic relaxation of both ventricles. Strophanthine was revealed to exert the prevailing effect on the cardiodynamics of the right ventricle both in intact dogs and in animals with experimentally induced pathology. Strophanthine increased pressure in the pulmonary artery, promoting the overload of the right ventricle to a less degree than convallotoxin. PMID- 4043370 TI - [Increased hepatocyte resistance to CC14 following the stimulation of rats with a bacterial polysaccharide]. AB - It has been established in male Wistar rats that the uptake capacity of the reticuloendothelial system (RES) increased 5-fold 1, 3 and 7 days after prodigiozan administration (50 micrograms). This was linked with the increased hepatocyte resistance to CCl4 which reached a maximum 7 and 21 days after RES stimulation. As compared with non-stimulated animals, the resistance increase looked as a 2.7- and 3.5-fold shrinkage of the necrotic zones in the central parts of liver lobules 24 h after CCl4 poisoning and less increment of alanine aminotransferase activity in blood serum (3.5- and 3.3-fold decrease, respectively). The increased resistance continued being recordable throughout a month after prodigiozan treatment. PMID- 4043371 TI - [Toxicological study of the Soviet tetracyclic antidepressant inkazan]. AB - The toxicology of an original Soviet antidepressant inkasan-3-methyl-8-methoxy 3H, 1,2,5,6-tetrahydropyrazino [1,2,3-ab] beta-carboline hydrochloride was studied in different types of experimental animals (mice, rats, rabbits, dogs). It was established that the drug is less toxic than imipramine. The toxic manifestations (seizures, stereotypy) seen in dogs receiving high doses of inkasan for a long time are likely to be linked with a stimulating component that characterizes the drug action on the central nervous system. PMID- 4043372 TI - [Quinolylhydrazones with potential antimicrobial and antiparasitic activity]. AB - Quinolinehydrazones prepared by condensation of hydrazinoquinolines with 1-phenyl 2,5-dimethyl-3-pyrrolcarboxaldehyde, 2-chloro-4-dimethylaminobenzaldehyde and 2,6 dichlorobenzaldehyde are described. All compounds were tested in vitro for antimicrobial activity, the results obtained are shown and discussed. The quinolinehydrazones of the 1-phenyl-2,5-dimethyl-3-pyrrolcarboxaldehyde were tested in vivo against Hymenolepis nana and Taenia taeniaeformis and proved inactive. PMID- 4043374 TI - [Antibacterial and antifungal compounds. V. Synthesis and antimicrobial activity of N-(2-arylethylaminophenyl)-1H-pyrryl-1-amine and 1-(1H-pyrrol-1-yl)-2 arylmethylbenzimidazole)]. AB - The synthesis and antimicrobial activities of derivatives of 1-anilinopyrrole and 1-pyrrylbenzimidazole are described. The compounds here reported can be related to chlormidazole and other antifungal imidazole agents. The antifungal activity of the new derivatives tested proved lower than that of ketoconazole; some compounds were practically inactive. PMID- 4043373 TI - Effect of chronic treatment with phosphatidyl serine on phospholipase A1 and A2 activities in different brain areas of 4 month and 24 month old rats. AB - The activities of phospholipase A1 and A2 were tested in mitochondria and microsomes from different cerebral areas of both 4 month and 24 month old rats, after 30 days i.p. treatment with ox Brain Cortex Phosphatidyl Serine (BC-PS). In the brain areas from control animals a rather great decline in its ability to hydrolize the fatty acids of the main phosphoglycerides was found. Taking into account only the effect of treatment with BC-PS on the modification of phospholipase activities caused by aging, we found that the treatment was able to balance the enzymatic functions altered by aging in several of the area examined. The importance of this result on the lipidic metabolism of the aging brain is also discussed. PMID- 4043375 TI - Synthesis and N.M.R. study of trans 2-phenoxycyclohexanol and some of its derivatives with potential antiinflammatory activity. AB - A number of amino-ethers, acids, amino-esters, amino-amides and carbamates was synthesized from trans-2-phenoxycyclohexanol. The configuration of the starting material was established by N.M.R. spectroscopy. Pharmacological tests showed an antiinflammatory activity for some of the derivatives. PMID- 4043376 TI - Antimycotic agents: evaluation of some derivatives of 2-thiocyanobenzoic acid. AB - The AA. have tested some amides, esters and thioesters of 2-thiocyanobenzoic acid for their antimycotic activity in vitro against fungal strains representative of human diseases. The results pointed out the remarkable antimycotic activities of 2-thiocyanobenzamides N-monosubstituted. PMID- 4043377 TI - Pyrrolnitrin analogues. XI--Synthesis and microbiological activity of new 1,4- and 1,5-diarylpyrroles. AB - The synthesis and microbiological activities of new 1,4- and 1,5-diarylpyrroles is reported. Antimicrobial data in comparison with fungal antibiotic pyrrolnitrin confirm an interesting antimicotic activity of 1,4-diarylpyrroles. On the contrary 1,5-diarylpyrroles show antibacterial activity and an unexpected antimicotic activity. The position of the 4-nitrophenyl group at C4 or C5 of the pyrrole ring influences antibacterial activity. PMID- 4043378 TI - Partial protection by CDP-choline against kainic acid-induced lesion in the rat caudate nucleus. AB - The acute intraperitoneal administration of CDP-choline to rats caused an increase in striatal dopamine (DA) synthesis, measured by DOPA accumulation after decarboxylase inhibition. Moreover, the chronic treatment with CDP-choline induced a decrease in the total number of 3H-spiroperidol binding sites, while partially antagonizing the disappearance of DA-sensitive adenylate cyclase activity elicited by intrastriatal kainic acid. These results suggest that CDP choline may have a trophic and/or stimulant action on the function of nigrostriatal dopaminergic neurons. PMID- 4043379 TI - Sodium-induced conformation changes in membrane transport proteins. AB - In the presence of KCl, tryptic digestion of vesicles derived from pigeon erythrocyte membranes inactivates sodium-dependent uptake of alanine by the vesicles, whereas digestion in the presence of NaCl does not. Extensive degradation of vesicle proteins occurs under both conditions. Similarly, the extent of inhibition by N-ethylmaleimide of the sodium-dependent influxes of both glycine and alanine into human erythrocytes is greater when the cells are exposed to the thiol reagent in the presence of KCl than when NaCl is used. These observations are interpreted as providing evidence for sodium-induced conformation changes in these transport proteins. PMID- 4043380 TI - A potential biochemical explanation for the genesis of porphyria cutanea tarda. Studies on the inherent biochemical defect in highly purified human erythrocyte uroporphyrinogen decarboxylase and its amplification by iron. AB - Familial porphyria cutanea tarda (PCT) is a photocutaneous disease in which subnormal activity of uroporphyrinogen decarboxylase is observed both in the liver and red cells. Hepatic iron plays a key role in the genesis of overt biochemical and clinical PCT. In this report, we have studied the properties of 10 000-fold purified erythrocyte uroporphyrinogen decarboxylase preparations from two familial PCT patients and a non-porphyric control subject. The apparent Michaelis constants (Km), determined by using uroporphyrinogen III substrate, were approx. 3.2-times higher for the enzyme from the diseased subjects (Km = approximately 1.0 microM) as compared to the normal (Km = 0.3 microM). Though both abnormal and normal enzymes were inhibited progressively with increasing concentrations of iron, the enzymes from diseased subjects exhibited greater susceptibility e.g. 0.1 mM Fe2+ inhibited the former about 50% and the latter about 20%. These observations suggest that the inherent biochemical defect in PCT is the reduced enzyme-substrate affinity and the intrinsic abnormal conformation renders the PCT enzyme particularly susceptible to inhibition by iron. PMID- 4043381 TI - Modification of mammalian fatty acid synthetase activity by NADP. AB - Experiments are described which show that the mammalian fatty acid synthetase, in the presence of NADP, synthesizes stoichiometric amounts of enzyme-bound acetoacetyl moieties. The acetoacetyl moieties can neither undergo the normal transfer reaction to a CoA acceptor, nor participate in the normal reaction sequence once NADPH is made available. Our results indicate that, since it is the product of the condensation reaction which accumulates on the inhibited enzyme, the previously held view that NADP inhibits the condensation step in fatty acid synthesis is probably incorrect. PMID- 4043382 TI - The role of metal ions in the uptake of aspartate aminotransferase and malate dehydrogenase into isolated rat liver mitochondria in vitro. AB - To gain further insight into the mitochondrial receptor area which allows selective uptake of both purified aspartate aminotransferase and malate dehydrogenase into mitochondria, the inhibition of metal complexing agents such as bathophenanthroline and tiron on the uptake of both enzymes has been investigated. In view of the nature of the inhibition found, we propose the existence of metal ion(s) at or near the aspartate aminotransferase, but far from the malate dehydrogenase binding site. PMID- 4043383 TI - Photosynthetic water oxidation. A new chemical model. AB - A sequential four-step chemical model for the water oxidation process in photosystem II is presented, based on the observation that a peroxide-linked biquinone complex can be chemically formed as a result of hydroxide ion addition to quinone. In our model, the hydroxide ion intermediate is generated in photosystem II as a result of proton abstraction from water. In the model, the first two flashes of light raise the oxidation state of the bimanganese center, while the third and fourth flashes of light sequentially generate the peroxide linked biquinone which is then directly oxidized by the bimanganese center to produce oxygen and regenerate quinone. PMID- 4043384 TI - Resonance Raman characterization of the heme prosthetic group in eosinophil peroxidase. AB - The resonance-enhanced Raman spectrum of eosinophil peroxidase (EPO) from horse and human eosinophils is reported. Based upon the spectral energies, distribution and depolarization ratios of the high-frequency skeletal modes and upon the presence of weak bands assignable to vinyl substituent groups, we conclude that the heme prosthetic group is high-spin, 6 coordinate protoporphyrin. The Raman spectrum reveals clear differences from lactoperoxidase (LPO), an enzyme which appears nearly structurally isomorphous by other physical techniques; the data indicate a stronger axial 6th ligand in EPO. Mechanistic implications are discussed in relation to LPO and myeloperoxidase, an enzyme present in neutrophils and monocytes which contains a unique functional active-site chlorin. PMID- 4043385 TI - A comparative study of structural properties of fibronectin and its 180 kDa fragment. AB - Fibronectin from human plasma and its 180 kDa fragment which retained collagen binding, cell-attachment and heparin-binding activities, were studied by velocity centrifugation and 1H-NMR methods. The fibronectin hydrodynamic radius strongly increased at pH 11 while the hydrodynamic properties of the fragment did not change noticeably. 1H-NMR spectroscopy also showed differences in the molecular properties of fibronectin and its 180 kDa fragment. Under physiological conditions the structure of fibronectin differs from that of its 180 kDa fragment. At pH 11 and in 4 M urea no differences in their structures are observed. It is suggested that interdomain and intersubunit interactions play an important role in maintaining the native conformation of intact fibronectin. PMID- 4043386 TI - Detection of the tripeptide Tyr-Gly-Gly, a putative enkephalin metabolite in brain, using a sensitive radioimmunoassay. AB - A sensitive and specific radioimmunoassay has been developed for YGG. The tripeptide was previously derivatised with p-benzoquinone to prepare the immunogen and the 125I tracer as well as in samples submitted to the RIA. The sensitivity is about 1 nM as compared with 8000 nM for underivatised YGG. Measurable amounts of endogenous YGG immunoreactivity, co-eluting in HPLC with authentic YGG, were detected in mouse striatal extracts. PMID- 4043387 TI - Resolution of bovine brain calcineurin subunits: stimulatory effect of subunit B on subunit A phosphatase activity. AB - Calcineurin was dissociated into subunits A and B by SDS and the dissociated subunits were separated by Sephadex G-100 column chromatography in SDS. The phosphatase activity was associated with the A subunit and was detected only in the presence of MnCl2 of the various divalent cations tested. The Mn2+-dependent phosphatase of A subunit was stimulated (4-5-fold) by calmodulin. The subunit B increased only modestly Mn2+ stimulated phosphatase activity of subunit A but markedly increased it when assay also contained calmodulin. These results support the view that subunit B plays an important role in Mn2+/calmodulin regulation of subunit A phosphatase activity. They also lend further support to our earlier postulate ([1984] FEBS Lett. 169, 251-255) that Mn2+ is a powerful regulator of calcineurin phosphatase. PMID- 4043388 TI - Poly-ADP-ribosylated histones: potent DNA suppressors. AB - When rat liver nuclear chromatin was sonicated in buffer containing 0.35 M (NH4)2SO4 to release the engaged RNA polymerases, a potent inhibitor was also released. This inhibitor elicited dramatic inhibition of RNA synthesis regardless of whether the free or engaged RNA polymerase was used. On further analysis, it became apparent that the site of inhibition was on the DNA template, not on the enzyme. This inhibitor could be extracted into 0.25 N HCl by the standard procedure for the isolation of histones. This acid-soluble inhibitor, showing typical histone band on gel, was RNase A and DNase I resistant, but was sensitive to both pronase and snake venom phosphodiesterase digestion, as well as to 0.1 N KOH hydrolysis. Furthermore, when [14C]adenine labeled poly-ADP-ribosylated histones were digested by snake venom phosphodiesterase, the release of radioactivity was in parallel to the loss of inhibitor activity. We conclude that the inhibitor substances are poly-ADP-ribosylated histones and propose that the poly-ADP-ribosylated histones rather than the histones are the natural suppressors of the gene. PMID- 4043389 TI - Stimulation of tyrosine phosphorylation of rat brain membrane proteins by calmodulin. AB - Calmodulin stimulates the alkali-resistant phosphorylation of peptides of 50 and 58-60 kDa in rat brain membrane. Phosphoamino acid analysis indicated a calmodulin stimulated increase of phosphotyrosine in these peptides. Calmodulin also stimulated the phosphorylation of these peptides at serine and threonine residues. This suggests the involvement of the calmodulin regulatory system in the effects of tyrosine protein kinases. PMID- 4043390 TI - Cytoplasmic pH, a key determinant of growth factor-induced DNA synthesis in quiescent fibroblasts. AB - In response to growth factors, quiescent fibroblast mutants lacking Na+/H+ exchange activity fail to elevate their cytoplasmic pH (pHi) and to reinitiate DNA synthesis at neutral and acidic pHo. A pHi threshold of approximately 7.2 exists, below which growth factors cannot set in motion the Go to S phase transition. Restoration of the pHi defect in mutant cells restores the wild-type phenotype. These findings, combined with the properties of another class of mutants able to grow at very low pHo, demonstrate that pHi, modulated by growth factor activation of the Na+/H+ antiporter, plays a determinant role in growth control. PMID- 4043391 TI - Discovery of a gamma-carboxyglutamic acid-containing protein in human spermatozoa. AB - Here we describe the identification of a gamma-carboxyglutamic acid-containing protein in human spermatozoa. After thermal decarboxylation the protein is a good substrate for vitamin K-dependent carboxylase from various origins. A quick purification procedure for the decarboxylated protein is presented and in a preliminary characterization we have established its Mr (28 000-30 000) and its amino acid composition. PMID- 4043392 TI - Presence of helodermin-like peptides of the VIP-secretin family in mammalian salivary glands and saliva. AB - Helodermin is a biologically active peptide isolated from the venom of the Gila monster lizard (Heloderma suspectum) whose structure is related to that of vasoactive intestinal peptide and secretin. Using a specific radioimmunoassay based on antisera prepared by immunizing rabbits with natural helodermin, we demonstrated the presence of helodermin-like material in mammalian salivary glands, including parotid, submaxillary and sublingual glands from rat and dog, and parotid and submaxillary glands from man. All helodermin-like materials had an apparent molecular mass of 4-12 kDa. Dog saliva, collected after pilocarpine stimulation, revealed similar immunoreactivity with a major component around 6 kDa. PMID- 4043393 TI - Effect of spectrin dimer on actin polymerization. AB - Spectrin dimer is shown to influence the polymerization behaviour of actin. The polymerization of both Mg2+- and Ca2+-actin is regulated by an enhancement in the rate of nucleation and a fragmentation of preformed actin filaments. In addition, spectrin decreases the critical concentration of Ca2+-actin but not that of Mg2+ actin. This suggests that the two types of actin may differ in their interaction with spectrin dimer probably due to the different conformations. Band 4.1 elevates the effects of spectrin under non-equilibrium conditions but its contribution is less at steady state. PMID- 4043394 TI - The 25 kDa protein kinase inhibitor present in liver cell is absent in fast growing HTC cells and is induced in sodium butyrate treated cells. AB - We have recently characterized a cAMP independent protein kinase inhibitor in rat liver. This inhibitor is absent or inactive in fast growing HTC cells and is induced according to exponential kinetics by sodium butyrate, a compound which arrests cell growth at the G1 phase of the cell cycle. It is suggested that the inhibitor could be involved in cell growth regulation. PMID- 4043395 TI - Acetylcholine stimulates phosphatidylinositol turnover at nicotinic receptors of cultured myotubes. AB - Acetylcholine treatment of [3H]inositol pre-labelled cultured chick embryo myotubes results in the stimulation of phosphatidylinositol breakdown, as shown by the measurement of inositol-1-phosphate accumulating in the presence of lithium. The described effect is dependent on agonist concentration and incubation time, and is inhibited by tubocurarine and alpha-bungarotoxin. The activation of phosphatidylinositol breakdown by acetylcholine at extrajunctional nicotinic receptors is likely to be involved in the modulation of the functional activity of the receptor. PMID- 4043396 TI - Muscarinic receptor-mediated increase in cytoplasmic free Ca2+ in isolated bovine adrenal medullary cells. Effects of TMB-8 and phorbol ester TPA. AB - The change in cytoplasmic free calcium, [Ca2+]i in isolated bovine adrenal medullary cells during stimulation by acetylcholine (ACh) in Ca2+-free incubation medium was measured using the fluorescent Ca2+ indicator quin2. ACh (1-100 microM) caused an increase in [Ca2+]i by mobilization of Ca2+ from the intracellular pool. Nicotine (10 microM) did not increase [Ca2+]i in the absence of extracellular Ca2+. Pretreatment of the cells with atropine (10 microM) completely inhibited ACh-induced increase in [Ca2+]i, whereas pretreatment with hexamethonium (100 microM) did not. The intracellular Ca2+ antagonist 8-(N,N diethylamino)octyl-3,4,5-trimethoxybenzoate (TMB-8), inhibited ACh-induced increase in [Ca2+]i. The activator of protein kinase C 12-O-tetradecanoylphorbol 13-acetate (TPA), but not its 'inactive' analog 4 alpha-phorbol-12,13-didecanoate (PDD), also inhibited ACh-induced increase in [Ca2+]i. These findings suggest that in bovine adrenal medullary cells, stimulation of muscarinic ACh receptor causes an increase in [Ca2+]i by mobilizing Ca2+ from the intracellular pool and that protein kinase C is involved in 'termination' or 'down regulation' of this response. PMID- 4043397 TI - Rapid down-regulation of protein kinase C and membrane association in phorbol ester-treated leukemia cells. AB - Peripheral blood lymphocytes from patients with chronic lymphocytic leukemia (CLL) acquire after several days of exposure to 12-O-tetradecanoylphorbol-13 acetate (TPA) several morphological, immunological and histochemical features of hairy cell leukemia. We have investigated the short term effects of TPA treatment on protein kinase C and its subcellular distribution. Within minutes of addition of TPA to CLL cells 20% of the cytosolic protein kinase C had associated with the particulate fraction. The remaining 80% of protein kinase C activity was down regulated. The association with the membrane dramatically increased the resistance of the enzyme to inhibition by the non-ionic detergent, Triton X-100. These results suggest that activation of protein kinase C causes multiple biological changes in CLL cells. PMID- 4043398 TI - Phorbol myristate acetate causes in guinea-pig lung parenchymal strip a maintained spasm which is relatively resistant to isoprenaline. AB - The effect of phorbol myristate acetate (PMA) was compared with that of histamine on the guinea-pig lung parenchymal strip. PMA, 10(-5) M, caused a slowly developing sustained contraction which had approximately the same magnitude as the maximal histamine contraction. Isoprenaline, at 10(-5) M, caused 86% relaxation of the histamine contraction but only 22% relaxation of the PMA contraction. Forskolin, at 10(-5) M had a similar action to isoprenaline on the effects of both spasmogens while aminophylline, 5 X 10(-4) M, was considerably less effective. Sodium nitroprusside had little effect on the histamine contraction and actually increased the PMA spasm. It is suggested that protein kinase C may have a role in the tonic phase of the contraction of bronchiolar smooth muscle. These findings could have relevance for the delayed phase of asthma, which is known to be insensitive to beta-agonists. PMID- 4043399 TI - Thermodynamics of the binding of calcium and strontium to bovine alpha lactalbumin. AB - Microcalorimetry and equilibrium gel filtration were used to determine the thermodynamic functions delta H degrees, delta G degrees and delta S degrees guiding the interaction of Ca2+ and Sr2+ with bovine alpha-lactalbumin. Two methods of nearly complete metal removal from the protein gave identical results. The single Ca- and Sr-binding site, which has moderate affinity for these ions (KCa = 2.5 X 10(6) M-1 and KSr = 5.1 X 10(5) M-1), displays unusually large enthalpy changes of -118 kJ X mol-1 for Ca2+ and -75 kJ X mol-1 for Sr2+. The concomitant reaction entropies equal -273 and -142 J X K-1 X mol-1, respectively. PMID- 4043400 TI - Studies on the maintenance of cytochromes P-450 and b5, monooxygenases and cytochrome reductases in primary cultures of rat hepatocytes. AB - The cytochrome P-450 content of rat hepatocytes declined rapidly over 72 h in culture, due primarily to denaturation to cytochrome P-420. Six different media were investigated for their ability to conserve cytochrome P-450 during culture, and the most successful was a modified Earle's medium. After 72 h culture in this medium, cytochromes P-450 and b5, NADH-cytochrome b5- and NADPH-cytochrome c reductases were maintained at 40, 100, 35 and 52% of fresh cell values, respectively. Cytochrome P-450 showed differential functional stability during culture with ethoxyresorufin O-deethylation being more stable than either pentoxyphenoxazone O-depentylation or biphenyl 4-hydroxylation. Monooxygenase than did cytochrome P-450 content. This discrepancy was not explained by loss of flavin nucleotides, FMN or FAD. PMID- 4043401 TI - Protein kinase C phosphorylates a component of NADPH oxidase of neutrophils. AB - A protein of 31.5 kDa belonging to the NADPH oxidase of neutrophils was phosphorylated following stimulation of the cells with phorbol myristate acetate. The same protein was phosphorylated in vitro in the presence of cytosol and of Ca2+ and phosphatidylserine. The phosphorylation in vitro of the 31.5 kDa protein was increased by phorbol myristate acetate and was inhibited by trifluoperazine. The data are compatible with an involvement of protein kinase C in the activation of NADPH oxidase. PMID- 4043402 TI - Kinetics of the reaction of intraerythrocytic haemoglobin by single cell microspectroscopy: effect of shape and osmolarity. AB - The kinetics of the reaction of CO with intraerythrocytic haemoglobin has been studied in single red blood cells (RBC) using a scanning microspectrophotometer and a photochemical perturbation method. Measurements have been carried out using red blood cells from man and camel (Camelus dromedarius), the latter at different osmotic pressures. Camel RBC, which are smaller and different in shape compared to human RBC, are known to remain intact even at an osmolarity 6-times lower than physiological (280-290 mosm/l), swelling up to twice their normal volume. The results show that the recombination time course is affected by diffusion of CO through a stagnant layer of solvent around the cell membrane, but that it is also influenced by other parameters such as intracellular diffusion of ligand and haemoglobin. PMID- 4043403 TI - Selected positions of acyl chains are affected differently by antibody binding which results in decreased membrane fluidity. AB - We have studied the interaction between monoclonal anti-trinitrophenyl antibodies (IgGl and IgG2a) and haptenated phospholipid vesicles using stopped-flow fluorometry. Conformational changes of the antibodies were induced very rapidly (within 0.1 s) after binding to lipid haptens (TNP-Cap-DPPE) on the membrane surfaces. Conversely, after that, the bound antibody molecules decreased the degree of molecular motion at different depths in the bilayer, ranging from the polar head group to the terminal methyl groups of the fatty acyl chains. Such an effect reaches all places of the bilayer within 40 s at 25 degrees C. PMID- 4043404 TI - Ovulation triggers oxytocin gene expression in the bovine ovary. AB - The gene for the nonapeptide neurohormone oxytocin is highly expressed in the bovine corpus luteum. Measurements of oxytocin-specific mRNA through the oestrous cycle of non-pregnant cows show that transcription is maximal accompanying ovulation and decreases rapidly thereafter. In contrast, immunohistochemistry shows neurophysin peptide levels to be greatest at mid-cycle. Low levels of oxytocin mRNA are detected in follicles and in the luteolytic half of the cycle. This mRNA is virtually absent in the corpus luteum of pregnant cattle. No cyclicity is evident in hypothalamic oxytocin mRNA levels. PMID- 4043405 TI - Release of T-kinin and bradykinin in carrageenin induced inflammation in the rat. AB - Plasma and inflammatory fluid kininogen levels, and blood and inflammatory fluid free kinin levels were determined in rats 24 h after the injection of carrageenin into an air pouch. Plasma T-kininogen levels increased 7-fold. In the inflammatory fluid levels reached 8 micrograms/ml. Blood levels of free kinin showed a 5-fold increase. The kinins were identified on HPLC as T-kinin (Ile-Ser bradykinin) and bradykinin, 63 and 37%, respectively. These results indicate for the first time that free T-kinin as well as bradykinin is released during an inflammatory response in rat and confirms our previous finding that T-kininogen may be a major acute-phase protein in inflammation. PMID- 4043406 TI - The myoglobin of rodents Proechimys guairae (casiragua) and Mus musculus (house mouse). AB - The amino acid sequences of the myoglobins of two rodents, the casiragua and the house mouse, have been determined. The myoglobin of casiragua differs from that of viscacha (another hystricomorph) at 6 positions. Mouse myoglobin differs from that of mole-rat (another myomorph) at 17 positions, whereas casiragua and mouse differ at 22 positions. Mouse myoglobin possesses several features unique among all known myoglobins (Gly 31, Cys 66, Thr 74 and Glu 113) and one substitution unique among known mammalian myoglobins (Glu 53). PMID- 4043407 TI - Heparin binding to lipoprotein lipase and low density lipoproteins. AB - Heparin was fractionated on an affinity column of bovine milk lipoprotein lipase (LpL) immobilized to Affi-Gel-15. The bound heparin, designated high-reactive heparin (HRH), enhanced LpL activity, presumably by stabilizing the enzyme against denaturation. The unbound heparin fraction had no observable effect on the initial rate of enzyme activity. However, at longer times of incubation there was inhibition of LpL activity. LpL-specific HRH also showed a high, Ca2+ dependent precipitating activity towards human plasma low density lipoproteins (LDL). Since LpL and LDL both bind to heparin-like molecules at the surface of the arterial wall, we suggest that their similar heparin-binding specificity may have physiological consequences as it relates to the development of atherosclerosis. PMID- 4043408 TI - Influence of platelet activation factor and prostaglandins on cholesterol esterification in human plasma. AB - Prostaglandin E1 (PGE1) and platelet activation factor (PAF) were found respectively to activate or to inhibit cholesterol esterification in whole plasma but not in lipoprotein-deficient plasma. It is suggested that these effects are mediated by the interaction of PGE1 and PAF with high-density lipoproteins [(1984) FEBS Lett. 173, 291-294]. Possible physiological implications of these findings are discussed. PMID- 4043409 TI - Functional heterogeneity of GEF-free initiation factor 2 purified from suckling and adult rat brain. AB - The functional behavior of initiation factor 2 was studied in purified preparations from the brains of suckling (4-12-day-old) and adult (60-day-old) rats. Adult eIF2 has lower GDP and GTP affinity than suckling eIF2, even in the presence of a large excess of GTP, whereas suckling eIF2 has a lower capacity to bind GTP. Since these two factors are free of guanine nucleotide exchange factor (GEF), and ribosomal fractions show an age-dependent difference in GEF activity, the observed functional heterogeneity may be due to a different ratio in eIF2 species (eIF2-GDP, eIF2(alpha P)). PMID- 4043410 TI - Different kinetic patterns in the alpha-chymotrypsin-catalysed hydrolysis of synthetic ester substrates. AB - The reaction of alpha-chymotrypsin with AcTyr-OEt and with AcTrp-OEt at pH 7.0 and 7.8 was studied over a wide range of substrate concentrations. The reaction with AcTyr-OEt at pH 7.8 was shown to be non-hyperbolic using a variety of criteria whereas those at pH 7.0 with the same substrate and at both pH values with AcTrp-OEt were hyperbolic. The non-hyperbolicity of the reaction with AcTyr OEt at pH 7.8 followed a pattern of negative cooperativity with a Hill coefficient for the high substrate concentration range of 0.48. Although other explanations are possible, the pH dependence of the reaction with AcTyr-OEt could be related to the slow transition of the two known forms of the enzyme. PMID- 4043411 TI - N-alpha-Tosyl-L-lysine chloromethyl ketone and N-alpha-tosyl-L-phenylalanine chloromethyl ketone inhibit protein kinase C. AB - TLCK (N-alpha-tosyl-L-lysine chloromethyl ketone) inhibits protein kinase C whether or not the enzyme is under the regulation of Ca2+ and phospholipid. TLCK (IC50 = 1 mM) is a much more potent inhibitor of protein kinase C than TPCK (N alpha-tosyl-L-phenylalanine chloromethyl ketone) (IC50 = 8 mM), suggesting that the lysyl moiety of TLCK may be specifically recognized by the active site of protein kinase C. These results extend the evidence that the active site of protein kinase C recognizes basic amino acids, and suggest that the active sites of protein kinase C and the cAMP-dependent protein kinase, which is also inhibited by TLCK and TPCK, are structurally related. PMID- 4043412 TI - [Effect of functional elimination of the hippocampus on learning and memory]. PMID- 4043413 TI - [Inhibition in neurons of the auditory cortex after rhythmic stimulation of geniculo-cortical fibers]. PMID- 4043414 TI - [Reaction of neurons of the neurostriatum to complex vocalization signals]. PMID- 4043415 TI - [Inhibition reaction of neurons of the chronically isolated strip of the associative cortex of cat brain (field 5) to intracortical electric stimulation]. PMID- 4043416 TI - [Effect of vasopressin on the cardiovascular system and electric activity of the hypothalamus in rabbits of various ages]. PMID- 4043417 TI - [Reaction of the central nervous system to diethyxime and phenobarbital after the application of triorthocresyl phosphate]. PMID- 4043418 TI - [Age-related changes in the membrane potential of stimulated cells, affecting the mechanism of active ion transport]. PMID- 4043419 TI - [Effect of low-energy laser irradiation on the dynamics of reparative processes in a peripheral nerve]. PMID- 4043421 TI - [Changes in the nature of unconditioned impulsive reactions of neurons of the limbic cortex after training in conditioned reflex]. PMID- 4043420 TI - [Effects of fasting and satiation monoamine levels in the brain]. PMID- 4043423 TI - [A device for determining experimental mechanical work performed by small laboratory animals]. PMID- 4043422 TI - [Effect of preliminary transplantation of autologous bone marrow on the development of experimental aortic lipidosis in rabbits]. PMID- 4043424 TI - [Diuretic and natriuretic functions of the kidneys of the rat during adaptation to cold]. AB - In cold acclimated male albino rats, in the cold the diuresis, glomerular filtration rate and water reabsorption were increased. These values did not differ from the control those. The kidney cold-induced diuresis was due to the increase of the glomerular filtration rate. The kidney excretion of the sodium was decreased during the cold adaptation both in the cold and in the heat. The decrease of the sodium excretion seemed to be due to the increase of the Na+-pump capacity in the kidneys. PMID- 4043425 TI - [Emotional stress-induced changes in catecholamines in the nuclei of the brains of rats differing in "open-field" behavior]. AB - The open-field test was used to study the role of initial emotionality in participation of brain catecholamines (CAs) in the BP control under emotional stress. The rats different in emotionality differed from each other in the level of CAs in single brain nuclei under normal conditions. Under stress, opposite CAs changes occurred in rats differing by their initial emotionality, in noradrenaline-synthetizing brain nuclei only. The neurochemical processes (features) which took part in the central BP control under stress were different in rats differing in their initial emotionality. PMID- 4043426 TI - [Catecholamines in nuclei of the brains of the August strain rat during immobilization stress]. AB - Changes in epinephrine, norepinephrine and dopamine levels in different brain nuclei of the August rats were studied after 6.5-hr immobilization. The linkage between the BP dynamics under emotional stress and changes of catecholamines content was observed in epinephrinsynthetizing area A1, norepinephrinsynthetizing area A6 (locus Coeruleus) and dopaminsynthetizing area A9 (substantia nigra). Sharp increase of the BP in the August rats was related to obvious decrease of epinephrine content in A1, norepinephrine in locus coeruleus and dopamine in substantia nigra. The data obtained suggest that deficit of the catecholamines due to the metabolic changes during emotional stress may result in distutbances of the cardiovascular functions control in the August rats. PMID- 4043427 TI - [Effect of sodium chloride on the properties of hemoglobin in the erythrocyte]. AB - The effect of iso- and hypertonic concentrations of sodium chloride (NaCl) on hemoglobin functional properties and acid-base balance in hemolysate, was studied. Washing of erythrocytes with 0.85% solution of NaCl decreased the pH and hemoglobin affinity to oxygen to such an extent that the Bohr effect increased as the result of effect of chloride ions on hemoglobin properties added to the effects of pH. PMID- 4043428 TI - [Changes in the functions of the blood vessels of skeletal muscles during acute hypothermia]. AB - In acure experiments on cats, changes of resistance, capacitance and filtration absorption functions of the m. gastrocnemius' vessels in acute cooling (from 37 degrees C to 29-27 degrees C) involved first a raise of the perfusion pressure in the vessels and its drop in further cooling to 25 degrees C. The pre- to post capillary ratio remained unchanged. Integral stretching ability of the venous bed was increasing along with the cooling. The capillary filtration coefficient was considerably increased. The capillary hydrostatic pressure increased in cooling to 27 degrees C and then decreased in further cooling to 25 degrees C. PMID- 4043429 TI - [Calcium current and electromechanical coupling in the smooth muscle cells of the stomach]. AB - The relationship between inward current and contraction was studied with double sucrose gap technique and measurement of contraction of the small muscular bundle in circular muscle from the fundus of guinea pig stomach. In voltage-clamped circular muscle, an inward current observed during depolarizing potential step was sensitive to Cd2+ or low external Ca2+ and had two components: a transient and a steady-state ones. Inactivation of this current was both voltage-dependent and Ca-current-dependent. Transient inward current activated phasic contraction, while the steady-state current activated tonic contraction. The voltage- dependence of the steady-state inward current was estimated with the Hodgkin- Huxley equation. PMID- 4043431 TI - [Detection of latent motor asymmetry of the brain in intact laboratory animals]. PMID- 4043430 TI - [Physiological properties of a protein factor isolated from the splenic tissue of the rat]. AB - The protein factor obtained from the rat spleen tissue inhibited non-enzymatic fibrinolysis and plasma anticoagulating activity both in vitro and in vivo. PMID- 4043432 TI - [Device for conjugate measurements of parameters of microcirculation and regional hemodynamics in the lungs]. PMID- 4043433 TI - Method for the preparation of plasmid DNA suitable for physicochemical measurements. AB - A method has been developed for the isolation of plasmid DNA suitable for physical and physicochemical measurements. The procedure is based on the deproteinization of the cleared lysate of bacterial cells (after amplification of plasmids by chloramphenicol) by phenol at pH 8.0 and subsequent removal of chromosomal DNA by means of phenol at pH 4.0 and separation of RNA on a hydroxyapatite column at higher temperature. ColE1 DNA sample was compared with samples of the same DNA prepared by three thus far used methods. Samples obtained by means of the latter methods were contaminated with chromosomal DNA, RNA, or ethidium bromide. The presence of ethidium bromide in the DNA sample was a factor interfering in the electrochemical analysis, chromosomal DNA and RNA were disturbing in the use of other methods. DNA separated by the method devised by us was free of any detectable contaminants and fulfilled the high requirements for sample purity of differential pulse polarography. Measurements performed by means of differential pulse polarography showed that the content of single-stranded segments in superhelical ColE1 DNA is less than 0.15% (i.e. less than 20 bases per molecule). This is in keeping with the notion that a cruciform is formed in this DNA (as a result of tension due to supercoiling) in the region of inverted repeat sequence, containing only 5 bases in the single-stranded loop region. PMID- 4043434 TI - Progesterone and androgen secretion by isolated cultured bovine corpus luteum cells: effect of LH, hCG, PRL, estradiol 17beta and testosterone. AB - Primary cell cultures of bovine corpora lutea were used in order to examine their morphology and secretion of progesterone and androgen in vitro. The cells were grown as monolayers up to 6 days at 37 degrees C medium 199 supplemented with 10% calf serum. The concentration of progesterone and androgen was measured using appropriate radioimmunoassays [1,3] respectively. Luteal cells were cultured with addition of the following amounts of hormones: 100 ng LH, 10 i.u. hCG, 100 ng PRL, 150 ng Estradiol 17 beta and 150 ng Testosterone/ml of culture medium. The luteal cells also created considerable amounts of androgens. It was found that only estradiol added to the culture medium caused an increase in the level of testosterone. Progesterone secretion following the addition of hormones increased under the influence of LH, T, and E2 in statistically significant manner while hCG and PRL had no statistically significant effects. PMID- 4043435 TI - Quantitative, qualitative and topographic distribution of lead, zinc, iron and copper in hard teeth tissues. AB - The objectives of the paper included a quantitative evaluation qualitative and topographic distribution of four microelements, namely lead, zinc, iron and copper, within enamel prisms, interprismatic region, tubular dentine, and intertubular dentine. The studies were carried out with the use of an X-ray microanalyser and an electron scanning microscope. The values of lead, zinc, iron and copper were higher in the enamel. Topographic curves for all the elements were similar within the enamel and dentin, characterized by unevenly distributed flat zero segments along with several peaks of diversified amplitude, being somewhat denser in the enamel. Qualitative distribution of the elements was also similar, and slightly denser within the enamel, the grains being unevenly scattered. PMID- 4043436 TI - The influence of the antimitotic drug CCNU on the neurosecretion of rat hypothalamo-hypophyseal system. AB - The purpose of this investigation was to evaluate the influence of the antimitotic drug CCNU on the morphology of the hypothalamo-hypophyseal neurosecretory system of rat. Adult Wistar rats were treated intragastrically with 2.5 mg CCNU once a week during 3 consecutive weeks and 5 mg at the end of the 4th week. The brains and hypophyses were fixed in Zenker-formol solution. Paraffin slices were stained with chromhematoxylin to demonstrate neurosecretory material and with cresyl violet. PAS reaction was also performed. The experiment resulted in disturbances of the neurosecretory function of the hypothalamo hypophyseal system in form of alteration in the content of neurosecretion in the neuronal cytoplasm and processes within supraoptic and paraventricular nuclei as well as in the neurohypophysis. The morphometric measurements showed enlargement of the cell nuclei and cytoplasm volumes in the nucleus supraopticus of hypothalamus. PMID- 4043437 TI - The role of the BCG dose and the mouse strain in the inhibition of development of neoplasms susceptible and nonsusceptible to the action of natural cytotoxic cells. AB - The susceptibility of Ehrlich Ascites Carcinoma (EAC) cells to the action of natural cytotoxic cells of DBA/2 and Balb/c mice in vitro was established. Leukaemia L 1210 cells proved insensitive to the in vitro action of natural cytotoxic cells of DBA/2 mice, but not to those of Balb/c ones. BCG, one of the inductors of cytotoxic NK cells, when administered to DBA/2 or Balb/c mice before introduction of EAC cells inhibited the growth of this tumour but did not retard the development of leukaemia L 1210 in DBA/2 mice. The change in the number of peritoneal exsudate cells (PEC) in DBA/2 mice after intraperitoneal injection of BCG was demonstrated to be dependent on the dose and the time elapsed after bacilli introduction. The antitumour action of BCG does not depend on changes in the number of PEC caused by the bacilli. Both large (3.0 mg) and small (0.02 mg) doses of BCG inhibit the development of EAC in Balb/c mice ("sensitive" to BCG), notwithstanding the time of administration of the bacilli. In DBA/2 mice ("resistant" to BCG) development of EAC can be inhibited only by the large dose of BCG since small one is sometimes ineffective. PMID- 4043438 TI - Temperature dependence of the dielectric properties of blood. AB - The aim of the work was to investigate the temperature effect in physiological range on the dielectric properties of a fish (Cyprinus carpio) blood. By applying an empirical non-damaging method and statistical analysis of the dielectric data, it is observed that a heating of carp blood induces an almost linear value variation of the electrical conductivity and permittivity of the intracellular matter of carp red blood cells. The dielectric data, however, reveal anomalous behaviour for conductivity and permittivity of the interior of carp erythrocytes at 23 degrees C and 23 degrees, 37 degrees C, respectively and for both volume fraction and dielectric loss factor tg delta at 30 degrees, 35 degrees, 37 degrees C. For the presented dielectric parameters the temperature coefficient and the Arrhenius activation energy were estimated. Moreover, this work led to conclusion that the changes of the volume fraction of carp erythrocytes induce corresponding variations of the maximum of the dielectric loss factor tg delta determined for a whole blood. PMID- 4043439 TI - Effect of simultaneous administration of ibuprofen and ethanol on the alkaline phosphatase activity in the small intestine. AB - Using the interferometric technique the authors studied the effect of simultaneous administration of ibuprofen (Polfa) and ethanol on the activity of alkaline phosphatase in the proximal jejunum. Both ibuprofen and ethanol cause in the digestive tract functional and morphological changes. The used technique of quantitative determination of alkaline phosphatase activity at the site of its primary location made possible an assessment of changes in the activity of the enzyme caused by the administered agents. It was found that after 60 days of the experiment both agents caused a statistically greater changes were observed in the rats receiving both these agents simultaneously. The obtained results suggest the conclusion that simultaneous administration of ibuprofen and ethanol causes in the mucosal gland in the proximal small intestine development of an interaction of the additive. PMID- 4043440 TI - Isolation of the homogeneous constituents from non-diffusible sugar-peptide (NSP) fraction originating from bovine plasma. IV. The influence on cell growth of REF and R-XC cells in vitro. AB - The effect of the NSP fraction and its four peptide constituents (A, C2, D and G) on the 3H-thymidine incorporation into REF and R-XC cells in vitro was described. Only peptide G (at concentration 5 micrograms/ml) affected the growth of the investigated cells, decreasing the 3H-thymidine uptake to 4-13% relative to untreated control, regardless of the kind of investigated cells. The effect of peptide G, added in concentration 10 ng-1 microgram, however was dependent on the type of investigated cells, suggests that neoplastic transformation changes the response of rat cells in vitro. The possible explanation of the differences in the biological response of the investigated cells to peptide G is proposed. PMID- 4043441 TI - A limited survey of retail apple and grape juices for the mycotoxin patulin. AB - A retail survey (38 samples) of apple, grape and other juice-based products for the mycotoxin patulin has been carried out using HPLC analysis. Positive results were confirmed by GC-MS of the TMS derivative using chemical ionization selected ion monitoring. No grape juice or mixed juice product contained detectable patulin (limit 5 micrograms/l), nor did the majority (58%) of the apple juices. Low levels of patulin (in the range 5-10 micrograms/l) were present in six apple juices and the remaining four positive samples contained 16, 18, 30 and 56 micrograms/l. PMID- 4043442 TI - Analysis, occurrence and control of Ochratoxin A residues in Danish pig kidneys. AB - In Denmark, porcine kidneys displaying macroscopic lesions of mycotoxic nephropathy are analysed for Ochratoxin A and the carcass condemned if the concentration exceeds 25 micrograms/kg. Since late 1982 these analyses have been conducted centrally. The reliability of the one-dimensional thin layer chromatographic method is discussed and results from an interlaboratory comparison are presented. From 1980 to 1984 there has been an overall decline in the rate of ochratoxicosis, interrupted in 1983 by a major increase geographically located in the northern half of Jutland. During that year 7639 kidneys were examined; 3% contained more than 150 micrograms/kg and 29% more than 25 micrograms/kg Ochratoxin A, corresponding to a condemnation rate of 15 per 100 000 slaughterings. The early stage of the increased incidence was characterized by kidneys with extremely high levels of the toxin; later most of the samples were negative or near-negative, as affected pigs were presumably fed a toxin-free diet before slaughtering. The efficacy of the control program is discussed in view of the 1983 data. PMID- 4043443 TI - The dietary significance of adventitious iron, zinc, copper and lead in domestically prepared food. AB - The uptake of iron, zinc, copper and lead by food cooked under domestic conditions in utensils made of different metals (cast iron, aluminium, plain and tinned copper) was investigated. It was found that the metal content of the food was generally related to the metal in immediate contact with the food during cooking. Daily dietary intake could vary from 11 to 6 mg of iron, 11 to 9 mg of zinc, 2 to 1 mg of copper and 0.4 to 0.1 mg of lead, depending on the cooking utensils used. Dietary intake of the metals was also related to sources and domestic practices regarding water supply. Consistent use of municipal water from a domestic hot water system could contribute a daily intake of 32 mg iron, 29 mg zinc and 12 mg copper. Rainwater stored in a galvanized iron tank could provide 23 mg of zinc per day when used for domestic purposes. The nutritional and toxicological significance of such adventitious sources of metals in the diet are discussed. The need to consider them when investigating the metal intake of individuals is stressed. PMID- 4043444 TI - Liquid chromatographic determination of the herbicide diuron and its metabolite 3,4-dichloroaniline in asparagus. AB - A liquid chromatographic method is presented for the determination of the phenylurea herbicide diuron and its major metabolite, 3,4-dichloroaniline in asparagus. The method involves a simple isolation step using dichloromethane extraction, followed by reversed phase chromatography on a C18 column, using a basic aqueous-organic eluent and UV detection at 254 nm. The limit of determination is 0.02 mg/kg for both analytes. PMID- 4043445 TI - Delaware's hazardous chemical law. PMID- 4043446 TI - Medical record linkage--we need it now! PMID- 4043447 TI - Medicine: the challenge of the 1990s. PMID- 4043448 TI - Spatial variation in migration processes and development: a Costa Rican example of conventional modeling augmented by the expansion method. AB - The ways in which migration and development have been linked in previous research in Third World settings are reviewed. Intercantonal migration in Costa Rica is analyzed, first in terms of a conventional model and then in terms of a paradigm of migration that focuses on place-to-place variations in development milieu. The results show there is spatial variation in the role of most variables and that these variations follow a reasonably consistent pattern with regard to development conditions. A series of maps graphically illustrates the importance of a spatial frame of reference. PMID- 4043449 TI - Variations in interstate migration of men across the early stages of the life cycle. AB - The results reported here show that the stage of an individual's life cycle not only has direct effects on the likelihood of migration, but also establishes a context within which the motives to migrate are evaluated and acted upon. One contextual impact of the life cycle concerns the effects of length of residence on migration. The results show that the probability of migrating declines more rapidly over time for married males with children than for singles males--i.e., the difference between the likelihood of migration for single males and married males with children widens with increasing length of residence. Much of this difference may be due to the greater number and strength of community ties for individuals who are married with children. These ties are not well developed at the beginning of a residence but continue to strengthen over the course of a residence. In addition, there are variations in the levels of job rewards and location-specific resources across the life cycle and there are two variations across the early life cycle in the effects of independent variables on the initial rate of migration. One resource (self-employment) and one job reward (prestige) have different effects for single individuals than for either group of married males. If the span of the life cycle considered in this analysis were broadened to include older men, additional differences in the effects of independent variables might be uncovered. In research with cross-sectional data containing a wider range of ages than the data used here, Heaton et al. (1981) found that economic variables were more important in determining the migration of younger individuals than that of older individuals, whereas noneconomic factors were more important determinants of the migration of older than of younger individuals. The results of this paper and Heaton's results suggest that at different stages of life people use a somewhat different "subjective cost-benefit calculus" in making migration decisions. The importance of certain migration determinants may vary significantly depending on whether an individual is married, whether he or she has children, and/or whether he or she is in the labor force or retired. Additional research on these issues could greatly contribute to our understanding of migration. PMID- 4043450 TI - Child support and welfare dependence: a multinomial logit analysis. AB - The relation between welfare dependency and receipt of child support is investigated with data from a special supplement to the Current Population Survey. The impact of receiving child support on a family's welfare status is estimated and the types of families for which child support enforcement policies may have the greatest impact are identified. Overall, the results indicate that receipt of child support has a modest impact on reducing welfare dependency. However, the results also indicate that if child support obligations can be established and enforced shortly after a marital dissolution takes place, the likelihood that a family will later become a welfare recipient is significantly reduced. PMID- 4043451 TI - Household structure and labor force participation of black, hispanic, and white mothers. AB - This paper investigates whether the inclusion of nonnuclear adults in a household facilitates the labor force participation of single and married mothers. Results based on a sample of extended and nuclear households show that the extension mechanism facilitates the labor market entry of married mothers, but not of single mothers. Interactions between extended structure, ethnicity, and poverty, however, suggest a complex relationship. For extended family households, the gender and employment characteristics of nonnuclear adults affected the labor force participation of single mothers, but the number of nonnuclear members was inversely associated with the market activity of married mothers. Policy implications are discussed in the final section. PMID- 4043452 TI - The effect of changing demographic composition on recent trends in underemployment. AB - The effect of changing age-sex composition on trends in unemployment and underemployment from 1969 to 1980 is estimated. This effect is positive as anticipated, but negligible in both absolute and relative terms. For example, no more than .35 percent of the increase in unemployment between 1969 and 1980 can be attributed to compositional factors. The secular rise in unemployment and underemployment from the late 1960s into the 1980s simply cannot be attributed in any substantial way to the changing demographic composition of the labor force. PMID- 4043453 TI - Reproductive impairments in the United States, 1965-1982. AB - The first national estimates of current fecundity status of women of all marital statuses indicate that, in 1982, about 5.1 million women were unable to have a future birth but would have liked to. About 2.7 million had difficulty bearing children, and the other 2.4 million were surgically sterile for noncontraceptive reasons. Since 1965, infertility was unchanged overall and in most age groups, but increased among wives aged 20-24. This paper explores a number of methodological and substantive questions related to reproductive impairments, such as the frequency of intercourse, the duration of infertility, and the possible causes of trends. PMID- 4043454 TI - An evaluation of the population and development program in Egypt. AB - Previous rural surveys analyzing the impact of the Egyptian Population and Development Program on KAP variables (knowledge, attitudes, and practices of contraception) have produced mixed results. In 1982 a survey specifically designed to measure program impact contained refinements in questionnaire measurement, sampling, and analysis. Each refinement intensified the apparent program impact. Fertility itself still appears unresponsive, and attitudes toward family size have changed little, but marked differences between program and nonprogram areas in contraceptive knowledge, attitudes, and practice suggest imminent fertility declines in program areas. PMID- 4043455 TI - Desired fertility, the "up to God" response, and sample selection bias. AB - An unresolved question in the analysis of survey data relating to fertility attitudes and beliefs is how non-numeric responses to questions on ideal family size should be treated. This paper demonstrates that simply dropping "up to God" responses will bias regression results. An unbiased estimator is presented which explicitly models the way in which observations are selected into the sample. The estimator is then employed on Guatemalan and Indian data. No support for the notion that women who answer "up to God" are women who would have given relatively large numeric answers is found in these two samples. PMID- 4043456 TI - On the dynamics of populations with two age groups. AB - By restricting the number of age groups to two and by introducing continued fractions, the dynamics of populations with deterministically changing vital rates are completely specified at all times. Explicit expressions for the sequence of the product of population projection matrices are given. From these, relative age distribution and reproductive values to any desired accuracy are obtained as functions of the vital rates. Thus, the results given in this paper are stronger than any existing weak ergodic theorems. PMID- 4043457 TI - The influence of certain clinical parameters on the immunoglobulin level in patients with simple psoriasis. PMID- 4043458 TI - [Removal of tattoos by excision and spontaneous epithelization under SYSpur derm]. PMID- 4043459 TI - [Cryptosporidium enteritidis. Occurrence in southern Lower Saxony. Study of urticaria as an example]. PMID- 4043460 TI - [Multiple basalomas as a late consequence of acute iatrogenic arsenic poisoning in childhood]. PMID- 4043461 TI - [Recommendation for a prescription of an emulsion for the care of sensitive and diseased skin]. PMID- 4043462 TI - Serum acid hydrolases in normal individuals and in patients with active plaque psoriasis. PMID- 4043463 TI - [Intrafollicular mollusca contagiosa]. PMID- 4043464 TI - [Folk medicine in Ethiopia. 3. Practical activities of a "traditional healer"]. PMID- 4043465 TI - [Is the somatotropic hormone of etiopathogenic importance in psoriasis?]. PMID- 4043466 TI - [Lipoma of brown adipose tissue]. PMID- 4043467 TI - [Contact dermatitis caused by Daphnia]. PMID- 4043468 TI - Sweet's syndrome and toxoplasmosis: a coincidental association? AB - A case report of febrile neutrophilic dermatosis as previously described by Sweet. The acute febrile illness is accompanied by plaque eruption and a positive toxoplasma indirect fluorescent antibody (IFA) test. Moreover, clinical and histopathological manifestations were compatible with the cutaneous reactive manifestation of toxoplasmosis and disappeared only after specific therapy. PMID- 4043469 TI - Multiple eruptive verrucous hemangiomas: a variant of multiple hemangiomatosis. AB - We present a case of an 8-year-old girl, who has, since birth, developed multiple angiomatous lesions of the skin. The evolution has been progressive and eruptive, with the lesions, beginning as reddish papulae, acquiring later a verrucous appearance. The case has revealed no associated systemic symptoms nor relevant family history of any interest. The clinical picture suggests multiple hemangiomatosis. The histopathology seems to relate this disorder to verrucous hemangioma, and therefore needs to be differentiated from angiokeratotic nevi. To our knowledge, reports of a similar clinicopathological picture are not mentioned in the literature. PMID- 4043470 TI - Malignant pyoderma. Report of a case associated with a disorder of the immune system. AB - A 41-year-old man developed multiple suppurative ulcers and subcutaneous inflammatory nodules and abscesses on the face, the trunk and the extremities. Repeated bacterial and fungus cultures gave nonspecific and inconstant results. Light-microscopic studies showed diffuse inflammatory reaction in the dermis with abscess formation and tissue destruction. There was no evidence of blood vessel inflammatory changes. The course of the disease was characterized by marked chronicity and partial response to systemic steroid and antibiotic therapy. Treatment with clofazimine resulted in a marked improvement of the lesions. Laboratory test results suggest that a deficiency of cell-mediated immunity, associated with increased concentrations of immunoglobulins, may have been the pathogenic event in this case. PMID- 4043471 TI - Acrosyringial epidermolytic papulosis neviformis. AB - A 42-year-old woman showed multiple verrucous papules on her right ring finger. Histology revealed a hyperkeratotic plug and epidermal foci of epidermolytic hyperkeratosis exclusively involving the intraepidermal sweat duct units. We propose the term acrosyringial epidermolytic papulosis neviformis or epidermolytic sweat duct nevus to define this unique entity. PMID- 4043472 TI - Cutaneous vasculitis in a patient with acute brucellosis. AB - A patient suffering from brucellosis developed maculonodular and purpuric lesions. The skin biopsy showed granulomatous vasculitis with no deposition of immunoglobulins and complement on the vessels. PMID- 4043473 TI - [Trichome]. AB - A 4 year-old boy presented an acute pruriginous dermatitis of the hands, forearms and abdomen. A skin surface biopsy revealed numerous trichomes, small prickles present on plants. These trichomes were those of prickly pears and stuck deeply in the skin, inducing an inflammatory reaction known as Sabra dermatitis. A number of plant dermatitides are due to the presence of trichomes such as those due to linden, primula, wild rose or nettle. PMID- 4043474 TI - Genetic susceptibility in pityriasis versicolor. AB - 300 patients with pityriasis versicolor, 168 males and 132 females, of different ages were included in this study. Each was subjected to a detailed structured questionnaire. All the available relatives had been examined. Pedigrees were constructed and segregation analysis was done using the mathematics of population genetics. The collected data showed genetic susceptibility which is inconsistent with any of the single gene defects but fulfill the criteria of multifactorial (genetic-environmental) inheritance. The heritability was estimated to be 22.2% in the first-degree relatives. PMID- 4043475 TI - Soft-X-ray therapy in Bowen's disease and erythroplasia of Queyrat. AB - The therapeutic results obtained with soft-X-ray irradiation on 77 lesions in 52 patients are reported. 35 males (67.3%) and 17 females (32.7%) were treated. Clinical and histological features revealed Bowen's disease in 73 cases (94.8%) and erythroplasia of Queyrat in 4 cases (5.2%). The primary healing was rated as 100% in all cases up to 6 months after a cumulative dosage of 3,200-5,000 R. 2 cases with a genital localization (2.6% of all sites and 11.1% of anogenital localizations) relapsed after 8 and 16 months, respectively. The follow-up period ranged from 1 to 11 years with a mean of 3 years. In order not to miss the late recurrences, the oncologic follow-up is taken care of by the Dermatology Department of the Zurich University Hospital during 10 years, or longer in some cases. Association with a malignant internal tumour (larynx, bronchi, anus) was found in 3 patients (5.8%). PMID- 4043476 TI - Combined UVB and UVA phototherapy of atopic eczema. AB - The effect of combined UVB-UVA treatment in a group of 23 patients with severe atopic eczema was compared to UVB therapy alone in 33 patients. Mean age and number of treatments were approximately the same in the two groups. With UVB-UVA treatment, 48% achieved complete remission and in another 48% good improvements were obtained as compared to 27 and 58%, respectively, in the group treated with UVB alone. A few failures were recorded in the UVB group. Some possible explanations for the better effect of the combined UVB-UVA treatment are given. PMID- 4043477 TI - [Post-traumatic proliferative myositis]. AB - A clinical and histological study of one case of proliferative myositis is reported. The relationship between that entity, and dermatofibromas and Dupuytren's disease are discussed. PMID- 4043478 TI - Terminological barbarisms overdue for retirement. PMID- 4043479 TI - Ontogeny of the invertebrate humoral immune response: studies on various developmental stages of the American cockroach (Periplaneta americana). AB - Earlier studies revealed that a specific adaptive humoral immune response can be induced in the American cockroach (Periplaneta americana) to the soluble protein complex, Honeybee venom (HBT). We have undertaken a series of ontogenetic studies to determine if there are differences between the protective responses of roaches representing different developmental stages. Our results indicated that the response to HBT in the immature cockroach (nymphs weighing 200-500 mg) was characterized by a significant lag period before immune protection began to develop. However, by the second week of the response, reactivity was comparable to that of the adult. Old adult male roaches (animals 5 months into adulthood) displayed a significant decline in reactivity during the early phases of the response in comparison to younger adults, and in general, appeared to be less vigorous in generating protection. Both the nymph and old adult roaches demonstrated good secondary responsiveness. The results from these experiments indicated that the developmental stage of the roach could be directly correlated to the degree of immunocompetency possessed by the animal. This is similar to the ontogenetic sequence typically found for immune reactivity in vertebrates. PMID- 4043480 TI - In vitro production of hydrogen peroxide by the amoebocytes of the scallop, Patinopecten yessoensis (Jay). AB - In vitro production of hydrogen peroxide (H2O2) by the amoebocytes of the scallop, Patinopecten yessoensis, was studied. The authors first confirmed the availability of the direct quantitative method using homovanillic acid, and found that both resting and stimulated amoebocytes produced H2O2. However, the latter showed higher capacity for H2O2 production. The amoebocytes stimulated by concanavalin A released a large amount of H2O2 compared with the cells challenged with three species of bacteria. PMID- 4043481 TI - Immunity to Aeromonas salmonicida in coho salmon (Oncorhynchus kisutch) induced by modified Freund's complete adjuvant: its non-specific nature and the probable role of macrophages in the phenomenon. AB - Juvenile coho salmon (Oncorhynchus kisutch), vaccinated with one intraperitoneal injection of formalin-killed virulent Aeromonas salmonicida cells suspended in saline, showed increased protection against approximately one LD60 of homologous challenge administered at 30 days post-vaccination. Under similar conditions, coho vaccinated with a modified complete Freund's adjuvant (MFCA) alone were also equally protected. When measured against a more severe A. salmonicida challenge of approximately one LD95, the strength of the MFCA-induced protection was found to exceed that produced by the homologous bacterin administered in saline or incomplete adjuvant, and the protection was still evident at 90 days post treatment. Other more precise measurements indicated the LD50 for MFCA-treated coho to be up to 450 times that for saline-treated coho. Two other tested adjuvants, levamisole and MDP (N-acetyl-muramyl-L-alanyl-D-isoglutamine), administered in a modified Freund's incomplete adjuvant, also enhanced anti-A. salmonicida immunity but to a lesser degree. The active factor in MFCA was a killed Mycobacterium butyricum preparation, and the anti-A. salmonicida immunity it induced was non-specific because the immunity extended to two other serologically distinct fish pathogens tested: A. hydrophila (LD50 increase of 5.3 fold) and Vibrio ordalii (LD50 increase of 560-fold). Macrophages are believed to account for the M. butyricum-induced anti-A. salmonicida immunity because the immunity was a) non-specific, b) very rapid in onset (it was measurable by 4 days), and c) influenced by particulate preparations, known to affect macrophage function and immunity in mammals. The possible benefits of adjuvant-induced non specific immunity in cultured fish are discussed. PMID- 4043482 TI - Cell-mediated immune response of Chelonia mydas. AB - Blastogenic and cytotoxic responsiveness of peripheral blood leukocytes from the green turtle, Chelonia mydas were examined. Blastogenic responses were low level and showed considerable variation between animals. Blastogenesis in response to phytohemagglutinin and concanavalin A was observed through out all seasons. Responses to pokeweed mitogen and lipopolysaccharide were seasonal, appearing in spring. No blastogenic response to protein A or allogeneic leukocytes was observed. Cytotoxic responses to phytohemagglutinin and antibody-dependent cell mediated cytotoxicity were of significant magnitude and, all animals responded in a similar manner. No spontaneous cytotoxic reactivity was observed. PMID- 4043483 TI - Differential effects of thyroxine on immune development and autoimmune thyroiditis in the obese strain chicken. AB - The effects of dietary thyroxine (T4) supplementation for specific periods on the early development of the primary lymphoid organs and spontaneous autoimmune thyroiditis (SAT) was examined in the Obese (OS) strain of chicken. Effects of the treatments on concentrations of serum growth hormone (GH) and testosterone were also determined. All treatment groups were examined at 6 weeks. T4 supplementation did not affect serum testosterone or GH concentrations. However T4 given for the first three weeks resulted in significantly increased bursa weights, no change in thymic weights, significantly decreased lymphoid infiltration of the thyroid and reduced thyroglobulin autoantibody levels (TgAAb). T4 supplementation for the full six weeks resulted in no change in bursal weight, significantly increased thymic weight, significantly decreased lymphoid infiltration of the thyroid, and reduced TgAAb. These results suggest that the effects of T4 supplementation on SAT and immune development are dependent on the interval during which it is administered and that testosterone and GH probably do not mediate these effects. PMID- 4043484 TI - The use of Ficoll-Hypaque double density gradients in the separation of avian granulocytes from other cell types for the purpose of cell flow cytometric analysis. AB - Avian peripheral blood and embryonic spleen cells were prepared for cell flow cytometry. The Ortho Spectrum III was the flow cytometer used in these experiments. The major objectives were to identify the location of lymphocytes and granulocytes in the cytogram displayed by flow cytometry, to develop a technique which would allow the collection of granulocytes relatively free of other cell types and to characterize the cell cycle within these cell populations. The cytogram of fresh avian cells developed in the Ortho Spectrum III revealed three characteristic cell clusters. Peripheral blood or embryonic spleen cells were separated on a Ficoll-Hypaque double density gradients into two distinct layers and a pellet. Light microscopic examination revealed the top layer of cells to be primarily lymphocytes while the middle layer of cells was granulocytes. Presentation of the cells from these layers to the Ortho Spectrum III revealed that granulocytes made up Cluster 3 while lymphocytes were included in the other clusters. The Ortho Spectrum III was employed to determine the presence of G1 (pre-DNA synthesis), S (DNA synthesis), and G2/M (post-DNA synthesis and mitosis) phases of cells in Clusters 1 and 2 and Cluster 3. While all the cells from peripheral blood were in G1, the embryonic spleen revealed cells in G1, S and G2/M in both Clusters 1 and 2 and Cluster 3. PMID- 4043485 TI - Phylogenetic origins of humoral immune mediators. Part I: The invertebrates. Symposium, Denver, December 29, 1984. PMID- 4043486 TI - Soluble mediators of cytolytic activity in hemocytes of the Asian clam, Corbicula fluminea. AB - Serum-free hemocytes from the clam, Corbicula fluminea, are cytolytic to mammalian erythrocytes (RBCs) as demonstrated in a hemoglobin release assay. The reaction is hemocyte dose- and temperature-dependent, and is mediated by the release of soluble hemolytic factors from clam cells. Initiation of hemocyte secretory activity does not appear to require contact with target RBCs. The chemical nature of the secreted lysin(s) has not been determined; however, PAGE analysis of hemocyte extracts (lysates) reveals the presence of at least five peaks of lytic activity. This activity is sensitive to heat and proteolytic enzyme treatment, and can be removed by absorption with fixed, homologous RBCs. Thus it is likely that the secreted hemocyte lysin is a heat-labile protein which exerts its hemolytic activity by binding directly to target RBC membrane constituents. PMID- 4043487 TI - Plasma components which mediate cellular defences in the gastropod mollusc Biomphalaria glabrata. AB - Blood plasmas from certain strains of Biomphalaria glabrata are known to have components which facilitate a hemocyte-effected cytotoxic response against encapsulated Schistosoma mansoni sporocysts. The possible identity of the factor(s) has been investigated. Sporocysts placed in snail plasma rapidly acquire a wide variety of host plasma antigens, at least some of which are displayed on the parasite surface. Plasmas from strains of snail resistant to the parasite agglutinate fixed sporocysts, while plasmas from susceptible strains fail to do so. Fixed sporocysts incubated in plasma bind selectively a subpopulation of plasma antigens; some are bound uniquely in resistant plasma. Another resembles a hemagglutinin from snail plasma. These and other recently acquired data are discussed in light of increasing evidence for defensive roles of multivalent lectins. PMID- 4043488 TI - Preliminary characterization of the inducible humoral factor in the American cockroach (Periplaneta americana). AB - Previous studies have defined an inducible humoral immune response in the American cockroach that demonstrates specificity and memory. In addition, the response is affected by the age and gender of the animal. Preliminary studies have been initiated to determine which of the protein components found in immune hemolymph might be responsible for mediating this activity. Comparisons between hemolymphs from immune and control animals, using SDS-PAGE gel analysis, revealed that there was a unique band generated in immune animals with an approximate MW of 162K. In addition, several other bands, with MWs of 220K, 115K, 102K, 95K, 80K and 77K, appear to be enhanced in immune hemolymph. The 240K, 220K and 115K bands were found only in females, and so have been temporarily excluded from further study because they were gender-dependent. When hemolymph samples were absorbed with HBT toxoid, the 162K band was no longer present in immune hemolymph, and the 115K, 102K, 95K and the 80/77K doublet were all greatly reduced as compared to controls. Analysis of supernatants from 24 hour cultures of cells from immune and BTS-injected animals, revealed that immune cells secreted the 162K, 102K, 95K and 80K bands. The 115K band was barely detectable, and the 77K band appeared to be missing. Thus, these studies have provided some valuable initial information that reduces the number of proteins that should be considered for further study as mediators of the roach inducible humoral response. PMID- 4043489 TI - Self blood glucose monitoring: evaluation of Haemo-Glukotest 20-800R, Visidex I and Reflolux. AB - Trained staff-members evaluated the accuracy of Haemo-Glukotest 20-800R (= HG 20 800R), Visidex I and Reflolux in 135 blood glucose measurements. A glucose oxidase method was used as reference method. Although the correlation between the 3 methods tested was excellent, more detailed analysis revealed for all methods a clear deviation from the real blood glucose, especially in the low blood glucose range. This might result in an inappropriate adaptation of the insulin dose, when the estimated blood glucose is used in connection with a classic algorithm. Apart from this limitation, Reflolux had the best accuracy, followed by HG 20-800R. If stored in a desiccated tube, the HG 20-800R strip can be reliably re-read (visually or with Reflolux) even after 7 days. Visidex I is unsuitable for storage and re-reading. PMID- 4043490 TI - Alloxan effects on mitochondria in vitro, studied with regard to inhibition of mitochondrial aconitase. AB - The recently observed inhibition by alloxan of mitochondrial aconitase was studied with regard to oxygen consumption, accumulated Ca2+ and volume of isolated mitochondria from mouse islets (not used for respiratory experiments), liver and kidneys. Altered respiration, efflux of Ca2+ and volume increase were induced in a manner dependent on the concentration of alloxan, the energetic state of the mitochondria, the addition of Ca2+ and reductant, and the type and concentration of substrate used. State 3 and, less pronounced, state 4 respiration were inhibited, accumulated Ca2+ was released, and the mitochondrial volume was increased at a minimum concentration of alloxan of 10-100 microM when pyruvate, citrate or cis-aconitate were substrates. The alloxan effects were less marked or absent when other substrates were used. The efflux of Ca2+ induced by alloxan in mitochondria respiring on pyruvate, citrate or cis-aconitate was inhibited or reversed by isocitrate. Potentiation of the alloxan effects was seen on increasing the concentration of alloxan, decreasing the concentration of substrate, addition of low concentrations of Ca2+ or reductant, and addition of alloxan before the substrate (non-energized state). The data support the finding of inhibition by alloxan of mitochondrial aconitase. PMID- 4043491 TI - Glycosylated serum proteins in diabetic patients and their relation to metabolic parameters. AB - Glycosylated plasma proteins (GSP) and some metabolic parameters (plasma glucose profile, urine glucose excretion, glycosylated hemoglobin, cholesterol, triglycerides) were evaluated in 70 diabetic and 70 normal subjects. Of the late diabetic complications, retinopathy, nephropathy and somatic neuropathy were evaluated. Proliferative retinopathy was observed in 41 of the 70 diabetics studied. No retinopathy or background retinopathy was observed in 29 diabetics. Nephropathy was diagnosed in 39 patients and somatic neuropathy in 44 patients; 26 diabetic subjects had no complications. GSP levels were 0.82 +/- 0.03 nmolHMF/mg prot in diabetics and 0.43 +/- 0.02 nmolHMF/mg prot in controls. GSP levels were positively correlated with metabolic parameters evaluated the same day and 14 days before. A positive correlation between GSP and triglycerides was seen for the first time. The patients with retinopathy showed levels of GSP significantly higher (p less than 0.001) in respect to patients with background retinopathy or absence of it (0.91 +/- 0.03 vs 0.74 +/- 0.04 nmolHMF/mg prot). GSP were significantly higher in the patients with somatic neuropathy (0.93 +/- 0.02 nmolHMF/mg prot) (p less than 0.001) than in the subjects without neuropathy (0.72 +/- 0.04 nmolHMF/mg prot). GSP levels were 0.92 +/- 0.03 nmolHMF/mg prot in diabetics with proteinuria and 0.75 +/- 0.04 nmolHMF/mg prot in diabetics without proteinuria (p less than 0.001). These results confirm the importance of GSP determination as another parameter of glycemic control and particularly as an index of the overall protein glycosylation processes. PMID- 4043492 TI - A screening procedure for diabetes in pregnancy. AB - A screening system for detection of diabetes in pregnancy was carried out in a geographically well-defined unselected population of 2 457 pregnant women all living in the community of Copenhagen. The screening was based on clinical criteria for potential diabetes consisting of previous delivery of a large baby, a family history of diabetes and obesity combined with examination of glucosuria and determination of the fasting blood glucose concentration. It was possible to follow up 95% of all pregnancies. One hundred and ninety women had a positive screening determination and among these women, 24 (1%) were found to have diabetes in pregnancy. It was established that a fasting blood glucose concentration of 4.1 mmol/l was the ideal cut-off point for referring potential diabetics to an oral glucose tolerance test (OGTT). The screening procedure is easy to administer and acceptable for the pregnant woman. The screening OGTT should be performed in the second or third trimester as only one woman had diabetes detected in the first trimester in this study. PMID- 4043493 TI - [Antihypertensive medication and glycoregulation]. PMID- 4043494 TI - [Diabetes and color vision]. PMID- 4043495 TI - Automatic measurement of walking speed and stride length. PMID- 4043496 TI - A static experimental stress analysis of a single plateau of the Geomedic knee joint using embedded strain gauges. PMID- 4043497 TI - Measuring devices for studying joint mobility in the normal population. PMID- 4043499 TI - Comprehensive creep behaviour of irradiated ultra high molecular weight polyethylene at 37 degrees C. PMID- 4043498 TI - Bone mineral assay: its relation to the mechanical strength of cancellous bone. PMID- 4043500 TI - Design of intramedullary femoral stems using computer graphics. PMID- 4043501 TI - A comparison of knee joint and muscle forces in women 36 weeks pregnant and four weeks after delivery. PMID- 4043503 TI - Processing of non-invasive signals from the fetal heart. Abstracts from the third workshop of the Working Group on Description and Evaluation of Cardiotocograms, European Community Project "Perinatal Monitoring", Heidelberg, 17-20 November 1984. PMID- 4043502 TI - Effects of fetal breathing movements on umbilical venous blood flow in fetal lambs. AB - The effects of fetal breathing movements on the blood flow pattern in the common umbilical vein were studied in six chronically instrumented fetal lambs between 106 and 143 days gestation. Umbilical venous blood flow was measured with an electromagnetic flow transducer around the intra-abdominal common umbilical vein. Fetal breathing movements were recorded by means of an intratracheal catheter. During rapid irregular breathing movements instantaneous umbilical venous blood flow showed undulations with the frequency of the breathing movements. An inspiratory movement, characterized by a fall in tracheal pressure (mean +/- S.D. = 5.3 +/- 1.7 mmHg) was accompanied by a decrease in instantaneous umbilical venous blood flow (mean +/- S.D. = 10.5 +/- 2.8%). This decrease in umbilical blood flow during inspiration was accompanied by an increase in intra-abdominal pressure. A much greater decrease (mean +/- S.D. = 40.6 +/- 18.4%) in instantaneous umbilical venous blood flow occurred during deep inspiratory efforts (mean pressure drop +/- S.D. = 15.5 +/- 4.3 mmHg), accompanied by marked increases in intra-abdominal pressure. Isolated expiratory efforts resulted in an increase in both tracheal (mean +/- S.D. = 6.3 +/- 2.6 mmHg) and intra-abdominal pressure, while umbilical venous blood flow decreased (mean +/- S.D. = 33.5 +/- 21.3%). These observations show the great influence of fetal respiratory movements on the blood flow pattern in the common umbilical vein. The changes in instantaneous umbilical venous blood flow are possibly brought about by changes in intra-abdominal pressure. PMID- 4043504 TI - Modulations in mouse hemopoiesis after engraftment with Lewis lung (3LL) carcinoma cells. AB - Hemopoietic changes in male C57BL/6Cum BR mice engrafted with Lewis lung carcinoma (3LL) were evaluated between day 7, when palpable tumors were present, to day 30 postengraftment. All experimental animals demonstrated decreasing hematocrits (down 40% by day 30) with concurrent leukocytosis which by day 30 postengraftment had reached levels 13.4 times normal. The myelocytic/erythrocytic ratio for normal animals was 1:3 (bone marrow: spleen). The ratio for engrafted animals ranged between 10:1 and 40:1. This apparent shift in production priorities is even more significant in light of the fact that femoral bone marrow cellularity had decreased by 33% on day 17. Splenomegaly, evident by day 7, was seven times control by day 17. Clonogenic analysis of erythroprogenitor cell concentrations revealed an inverse relationship between bone marrow and spleen. 27 days after engraftment, splenic populations demonstrated significant increases in colony forming unit-erythroid (115-fold), burst forming unit-erythroid (7.4 fold), whereas bone marrow concentrations had decreased (6-fold). This report suggests that initiation of 3LL tumor in mice results in a change in the degree of hematopoietic priorities and participation of erythroid organs. PMID- 4043505 TI - Biological activity of synthetic subunits of streptococcus peptidoglycan. III. Relationship of subunit and analogue structure to adjuvant activity in cell mediated immunity. AB - Each of a series of synthetic peptidoglycan subunits and subunit analogues was injected in combination with streptococcus type M24 antigen extract. The substances tested were: (8a) N-acetylmuramyldipeptide (MDP) and the following derivatives thereof: MDP modified in positions C3 and C4, or with L-alanine substituted by L-2-aminobutyric acid or with the peptide chain prolonged (by three lysines or a polylysine); (b) some synthetically prepared peptides: a hexapeptide, a tridecapeptide and an octadecapeptide. Configurations in positions C3 and C4 were found essential for the adjuvant effect. Adjuvant activity, though somewhat lower than in MDP, was pronounced in the analogue containing the L-2 aminobutyryl residue. Surprisingly, potent adjuvant effect was displayed by the hexapeptide; prolongation of the peptidic chain was not effective. The use of a polymeric carrier for MDP increased the adjuvant effect. Contrary to expectation, streptococcal antigens used with immunoadjuvant materials showed that induced delayed hypersensitivity was type related. PMID- 4043506 TI - Response to ionizing radiation of human bladder transitional cell carcinomas grown in the nude mouse. AB - The sensitivity to ionizing radiation of three human bladder transitional cell carcinomas grown in the nude mouse was investigated at four different radiation levels, 500, 1,000, 2,000 and 4,000 rad. Each tumor line exhibited a response pattern which reflected to a certain degree tumor differentiation and growth rate in the nude mouse. Exposure to 1,000 rad was the minimum amount of radiation required to produce a distinct, although transient, tumor response in all three tumor lines characterized by a growth delay of 3-4 weeks, whereas maximum tumor response was observed at the 4,000 rad radiation level. These studies would permit a better understanding of the behavior of human bladder cancer to ionizing radiation and may further facilitate efforts at identifying effective radiosensitizing agents that may result in maximizing tumor response. PMID- 4043507 TI - Effects of ethanol on the lipid composition of bovine vascular smooth muscle cells in culture. AB - Ethanol (50 mM) had no effect on the growth rate or viability of arterial smooth muscle cells over 3.5 days. The cholesterol:phospholipid ratio of the cells was unchanged after 7 days exposure. The major phospholipid components phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine and phosphatidylinositol were unchanged by ethanol exposure. Sphingomyelin content fell significantly within 12 hr. There were major changes in the fatty acid composition of the phospholipids with a reduction in saturated fatty acids and an increase in unsaturated fatty acids. PMID- 4043508 TI - Hydrophobic photolabelling of sarcoplasmic reticulum with [125I]TID. AB - [125I]TID, a small photoreactive lipophylic reagent, was used to label intrinsic proteins of rabbit and rat sarcoplasmic reticulum membranes. A 160,000 glycoprotein, the Ca2+-ATPase and polypeptides of mol. wt 53-55,000, 30,000, 20,000 and 6000 dalton were labelled suggesting that these proteins are integral membrane components. PMID- 4043509 TI - A comparison between effects of chronic ethanol consumption, ethanol withdrawal and fasting in ethanol-fed rats on the free cytosolic NADP+/NADPH ratio and NADPH regenerating enzyme activities in the liver. AB - Effects of chronic ethanol consumption, withdrawal and fasting on the free cytosolic NADP+/NADPH ratio and NADPH-regenerating enzyme activities of rat liver were studied. Ethanol consumption was shown to decrease the NADP+/NADPH ratio in non-fasted rats, and both ethanol withdrawal and fasting in ethanol-fed animals appeared to increase the ratio to the normal or higher level. Any treatment of rats caused the complex interaction on hepatic NADPH-regenerating enzyme activities, none of the enzyme activity correlating with the free cytosolic NADP+/NADPH ratio. Relationship between free cytosolic NADP+/NADPH ratio and lipogenic capacity of withdrawn rat liver is discussed, and a hypothesis for development of the fatty liver is suggested. PMID- 4043510 TI - Differences in the mode of iodination of H2a variants in chromatin. AB - Modification of H2a variants with radioactive iodine was used to study under different ionic conditions the accessibility of their tyrosine residues in chromatin, in monosomes and when free in solution. The modification of tyrosine 57 in the hydrophobic part of H2a was found responsible for the appearance of new fractions with a reduced electrophoretic mobility in the presence of Trition X 100, detected only by autoradiography (radioactive "ghosts"). At low ionic strength a very small number of molecules were iodinated in chromatin, the modification affecting only their hydrophobic region. At moderate ionic strength the tyrosine residues near the N-terminal region of the molecule were predominantly modified. In chromatin the accessibility of the tyrosine residues of H2a1 was much greater than that of H2a2, a difference not observed with free histones. PMID- 4043511 TI - Analysis of iron-binding components in the low molecular weight fraction of rat reticulocyte cytosol. AB - Rat reticulocytes were incubated with rat 125I-Tf-59Fe under conditions inhibiting heme synthesis. Cytosol, prepared from the reticulocytes, was separated and analysed by gel filtration and Amicon Ultrafiltration. An iron containing low molecular weight fraction derived from the cytosol was further analysed by HPLC size-exclusion chromatography and HPLC reversed phase chromatography. Conditions inhibiting heme synthesis and uncoupling the oxidative phosphorylations lead to a large increase in the Fe-containing low molecular weight fraction in the cytosol. The components in the low molecular weight fraction have an apparent molecular weight of 5500 Dalton as determined with HPLC size-exclusion chromatography. The low molecular weight fraction contained several iron chelating components like glycin, 1/2 cystine and citrate, but no specific iron-binding proteins, nucleotides or pyrophosphate. PMID- 4043512 TI - Effect of phosphate and other inorganic anions on the activity of chicken liver cytosolic aspartate aminotransferase. AB - Chicken liver aspartate aminotransferase was inhibited by several inorganic anions. The inhibitory effect of the anions was related to their chaotropic character. Apparent Km (2-oxoglutarate) and Km (L-aspartate) values depended on the molarity of the buffer. The profile of the curves obtained did not depend on the nature of the enzyme sample assayed. Phosphate slightly inhibited the holoaspartate aminotransferase and was a strong inhibitor of apoaspartate aminotransferase with respect to pyridoxal phosphate. PMID- 4043513 TI - Inhibition of experimental porphyria with colchicine. AB - Colchicine at the concentrations of 5 X 10(-7) - 5 X 10(-6) M decreased significantly both delta-aminolevulinic acid synthase activity and accumulation of porphyrins in monolayers of chick embryo liver cells induced by allyl isopropylacetamide, by 3,5-diethoxycarbonyl-1,4-dihydrocollidine or by phenobarbitone. No effect was noted in non-induced cells. In rats, colchicine 0.3 mg/kg, reduced significantly the allyl-isopropylacetamide induced increase in the activity of delta-aminolevulinic acid synthase in the liver and the concentration of urinary porphyrins while it did not affect these parameters in non-induced rats. PMID- 4043514 TI - Contraceptive social marketing: lessons from experience. PMID- 4043515 TI - Social marketing of oral rehydration therapy. PMID- 4043516 TI - Comparison of the efficacy of furosemide with two furosemide-triamterene combinations in the treatment of cardiac insufficiency. AB - Nine patients suffering from cardiac insufficiency were given furosemide and two furosemide-triamterene combination products in random order. A statistically significant diuretic response was achieved with all these preparations. The combination of furosemide and triamterene brought about a 'softer' diuresis, no hypokalaemia and the advantage of dosage as only one tablet, thus eliminating the need for taking two separate drugs. PMID- 4043517 TI - Food poisoning--fact or fiction? An observation of the current interpretation of the term 'food-poisoning'. AB - The Communicable Disease Report number 84/52 has given a clear indication that Campylobacter infections are now the most significant reported causes of gastrointestinal infection. The figures given indicate approximately 22,000 Campylobacter infections in 1984 as opposed to approximately 14,000 Salmonella infections, with, more importantly, the trend increasing with regard to Campylobacter, and decreasing with regard to Salmonella infections. Campylobacter enteritis would now appear to be a major problem both in terms of human suffering and in its economic effects. It is reported, for example, that at least 80,000 working days may be lost in the United Kingdom per year. The fundamental problem raised by Campylobacter enteritis is whether we need to have a standardized definition of food poisoning accepted in law to allow central government and local authorities to manage in particular the problems related to Campylobacter enteritis. From information available, it appears that local authorities have differing interpretations as to the classification and subsequent management of Campylobacter enteritis. In order to control the identified trend in the increase of Campylobacter infections, the need for a clear and explicit definition is rapidly becoming essential. PMID- 4043518 TI - Comparison between inhibin from human and bovine ovarian follicular fluid using fast protein liquid chromatography. AB - Inhibin from human and bovine ovarian follicular fluid was purified 700-900-fold using affinity chromatography on immobilized Procion Red 3B, desalting on Sephadex G-25, ion-exchange chromatography on the fast protein liquid chromatography (FPLC) columns Mono Q and Mono P and chromatography on immobilized lectins. Isoelectric points for inhibin from human and bovine origin were between 5.1-5.7 and 4.75-5.25, respectively. Inhibin from both sources was retained by immobilized lectins, indicating its association with a glycoprotein. Overall recoveries of inhibin activity after these chromatographic procedures were approximately 1%. PMID- 4043519 TI - Localization of liver-type lipase in rat ovaries and its activity during the estrous cycle and lactation. AB - The conditions for an in vitro assay of liver-type lipase, i.e. an enzyme resembling the lipase releasable from the liver by heparin (liver lipase), in rat ovaries were established. The liver-type lipase activity in the ovaries was almost completely (greater than 95%) located in the corpora lutea and its activity ranged from 0.44 to 0.77 mU per corpus luteum of (pseudo)pregnant rats. Preovulatory ovarian follicles contained very low lipase activity. During the estrous cycle the pattern of lipase activity was similar to that of serum progesterone levels (maximal at diestrus 1 and minimal at diestrus 2). In the individual rats liver-type lipase activity in the ovaries was strongly correlated with serum progesterone and 20 alpha-hydroxyprogesterone. The activity of liver type lipase also varied during lactation. It was relatively low at an early stage (2-3 days) but increased during later stages of lactation. The serum progesterone level was relatively low in rats lactating for 2-3 or 22-24 days. During the intervening time, its concentrations was elevated. Since serum 20 alpha hydroxyprogesterone levels varied inversely to progesterone, the total amount of progestagens in blood during lactation remained constant. The cholesterol content of the corpora lutea of the lactating rats was initially high and decreased during the lactation. PMID- 4043520 TI - Mammotroph autoregulation: intracellular fate of internalized prolactin. AB - As part of a study concerning the mechanism of mammotroph autoregulation, the intracellular fate of [125I]iodo rat PRL, internalized by mammotrophs, was determined by quantitative electron microscope autoradiography. Simple grain density (GD) analysis of mammotroph autoradiograms showed that 5 cellular compartments (plasma membrane, Golgi apparatus, secretory granules, nucleus and mitochondria) were significantly labeled and that the labeling pattern in these compartments changed with time. Inclusion of a 25-fold excess of unlabeled PRL inhibited the binding of radiolabeled hormone to mammotrophs by approximately 85%. At no time were any grains found associated with lysosomes and there was no evidence of degradation of the radiolabeled PRL as judged by SDS-polyacrylamide gel electrophoresis or cold perchloric acid precipitation of cell extracts or media samples. Delivery of internalized PRL to a number of specific intracellular organelles suggests that these organelles may serve in the autoregulation of PRL secretion. PMID- 4043521 TI - The International Standard for Human Growth Hormone for Bioassay: calibration and characterization by international collaborative study. AB - Two preparations of human growth hormone (hGH) were prepared as candidates for the International Standard for Human Growth Hormone for Bioassay and were studied by 22 laboratories in 10 countries in an international collaborative study. The 2 candidate preparations, freeze-dried in ampoules coded 80/505 and 80/521, were assayed against the International Standard for Growth Hormone, bovine, for Bioassay (ISbGH), by in vivo assays; against the International Reference Preparation of Growth Hormone, human, for Immunoassay (IRP hGH), by receptor-, immunoassays and other in vitro methods; and against each other by various methods. Both preparations contained the 2 recognized main growth hormone components (22 kDa and 20 kDa forms) and other components, but that in ampoules coded 80/505 had less deamidated hGH and contaminant hormones and pyrogen than that in ampoules coded 80/521. The estimates by in vivo bioassays, using immature hypophysectomized rats, of the potency of 80/505 in terms of the IS bGH were heterogeneous (1-6 IU/ampoule), probably because of the dissimilarity of the preparations of bovine and human GH. Estimates with receptor- and immunoassays of 80/505 against the IRP hGH were also heterogeneous (3-9 IU/ampoule). Nevertheless, the majority of estimates from all assays tended to be between 3 and 6 IU/ampoule. Although 80/521 and 80/505 differed in relatively minor respects, assays of one directly against the other gave relative potency estimates with in vivo assays which were significantly different from estimates with in vitro methods. With the agreement of the participants in the study, the WHO Expert Committee on Biological Standardization established the preparation in ampoules coded 80/505 as the First International Standard for Human Growth Hormone for Bioassay, with the defined potency of 4.4 IU/ampoule. This corresponds to an approximate 2.5 IU/mg of hGH extract and maintains reasonable continuity of the unit. PMID- 4043522 TI - Localization of mRNAs in mouse testes by in situ hybridization: distribution of alpha-tubulin and developmental stage specificity of pro-opiomelanocortin transcripts. AB - Gene expression of mouse testicular germ cells and surrounding somatic cells during spermatogenesis was examined by RNA:cDNA hybridization in situ and concomitant Northern and dot blot analysis. Particular attention was paid to obtaining fixation and hybridization procedures for use with mouse testes to accomplish sensitive and precise localization with the in situ technique. alpha Tubulin mRNAs were localized in virtually all testis cell types. In elongating spermatids, a unique labeling pattern was visualized; possibly corresponding to the position of the asymmetrically displaced cytoplasm. Pro-opiomelanocortin (POMC) transcripts in the adult mouse testis detected by Northern blot analysis were shown to be of a smaller size (approximately 600-800 nt) than the pituitary POMC transcripts, similar to what has been reported recently for POMC expression in the rat testis and mouse Leydig cell lines. Localization of POMC mRNAs by in situ hybridization was primarily to Leydig cells, although some labeling of spermatogonia and spermatocytes within the seminiferous epithelium was detected. A cellular or developmental specificity of the pattern of POMC localization was observed: obvious labeling of Leydig cells was limited to interstitial regions which were surrounded completely or in part by tubules in stages IX to XII of the cycle of the seminiferous epithelium. PMID- 4043523 TI - Plasticity in the cockroach neuromuscular system. AB - The retrograde transport of wheat germ agglutinin-conjugated horseradish peroxidase extracellularly injected into a leg muscle was used to identify the regenerating cockroach motor neurons that have grown an axonal branch into that muscle. At least 66% of the animals with crushed nerve roots eventually reform the original innervation pattern of this muscle with no mistakes. In spite of this apparent specificity the cockroach neuromuscular system can express plasticity as evidenced by the correction of mistakes made at early stages of regeneration. These mistakes are corrected through elimination during the time interval between 40 and 60 days after nerve crush. In addition, when the distal segments of the leg are removed, thus depriving some motor neurons of their normal target muscles, many of them form stable inappropriate axonal branches in denervated as well as fully innervated muscles. These observations are discussed in terms of possible mechanisms responsible for the specificity of the cellular interactions and in terms of their relevance to understanding the development of vertebrate neuromuscular systems. PMID- 4043524 TI - Muscle development in the grasshopper embryo. I. Muscles, nerves, and apodemes in the metathoracic leg. AB - Much is known about the development of nerve pathways in the metathoracic limb bud of the grasshopper embryo. In this series of three papers, we report on the development of muscles in the same embryonic appendage. In a fourth paper (E. E. Ball, R. K. Ho, and C. S. Goodman, 1985, J. Neurosci, in press) we examine the development of specific neuromuscular connections for one of these muscles (coxal muscle 133a). In this first paper, we present an overview of the development of muscles, nerves, and apodemes (tendons). We previously reported on a class of large mesodermal cells, called muscle pioneers (MPs), that arises early in development and appears to act as a scaffold for developing muscles and guidance cue for motoneuron growth cones (R. K. Ho, E. E. Ball, and C. S. Goodman, 1983, Nature (London) 301, 66-69). We have used the I-5 monoclonal antibody (which specifically labels the MPs as well as the nerve pathways), HRP immunocytochemistry, and Normarski optics to visualize muscle, nerve, and apodeme development in the embryonic metathoracic limb bud from 27.5% (before the appearance of the MPs) to 55% (after the muscles have attained their basic adult pattern). Cell fusions, cell migration, and cell death all appear to play important roles in the development of MPs. The patterns of muscle development vary greatly, ranging from (i) single MPs for simple muscles (which in the adult have only one bundle of muscle fibers, e.g., coxal muscle 133a), to (ii) arrays of MPs for complex muscles [which in the adult have many bundles of muscle fibers each with separate sites of insertion, e.g., the extensor tibiae (ETi) and flexor tibiae (FlTi) muscles in the femur]. PMID- 4043525 TI - Muscle development in the grasshopper embryo. II. Syncytial origin of the extensor tibiae muscle pioneers. AB - The extensor tibiae muscle (ETi) in the metathoracic leg of the grasshopper, which powers the jump, is among the most studied insect muscles. In contrast to many insect muscles which are simple (consisting of only a single bundle of muscle fibers), the ETi is a complex muscle which consists of an array of bundles of muscle fibers, each with a separate site of insertion on the body wall ectoderm and on the ETi apodeme ectoderm. Here we describe the embryonic development of this complex muscle. The ETi muscle develops from a single muscle pioneer (MP) which connects the initial invagination of the ETi apodeme to the wall of the femur. This MP then dramatically expands around the developing apodeme to form a large horseshoe-shaped, multinucleate cell, called the supramuscle pioneer (supra-MP); the number of nuclei in the supra-MP increases by cell fusion rather than by nuclear division. The arms of the supra-MP grow steadily longer and their outer edges begin to appear scalloped, certain areas remaining tightly apposed to the ectoderm of the wall of the leg while adjacent areas lose their adhesion and are pulled away. By about 50% of embryonic development the ETi supra-MP consists of a periodic series of bridges (cytoplasmic extensions) connecting the leg wall ectoderm with the apodeme, and linked into a giant syncytium near their inner, apodeme surface by a thin layer of cytoplasm containing hundreds of nuclei. Each bridge is surrounded by a cluster of many smaller mesoderm cells. Next the syncytium begins to divide such that by 60% the periodic bridges of the supra-MP have lost syncytial contact with each other and now themselves form an array of smaller, individual, multinucleate MPs connecting the body wall to the apodeme, each surrounded by a mass of undifferentiated mesoderm cells. This initial cycle of fusion and division is followed by a second similar cycle in which the individual mesoderm cells surrounding each MP fuse with the MP. At the same time, the MP divides into the initial bundle of smaller muscle fibers. Coincident with this division into muscle fibers is the further development of thick and thin filaments and the T tubule system. PMID- 4043526 TI - Muscle development in the grasshopper embryo. III. Sequential origin of the flexor tibiae muscle pioneers. AB - The flexor (FlTi) and extensor (ETi) tibiae are antagonist muscles located in the femur of the metathoracic leg of the grasshopper. Both are complex, consisting of an array of bundles of muscle fibers connecting the ectoderm of the wall of the femur with their respective apodemes. In the previous paper (E. E. Ball and C. S. Goodman, 1985, Dev. Biol. 111, 399-416) we described the embryonic development of the ETi muscle, focusing in particular on its syncytial origin from a giant supramuscle pioneer which later divides into an array of individual muscle pioneers. Here we describe the embryonic development of the FlTi muscle. In contrast to the development of the ETi muscle, the array of individual muscle pioneers for the FlTi does not have a syncytial origin but rather arises by sequential recruitment from the mass of smaller, undifferentiated mesoderm cells. The FlTi MPs first appear as two cells symmetrically placed on the corners of the FlTi apodeme at around 37%. A third MP is then added between these two; this third MP later dies. Subsequent growth occurs by symmetrical addition of MPs distally along the sides of the developing apodeme and by enlargement of the individual MPs. Initially each MP contains only a single nucleus; by about 50% there are at least two to three nuclei per MP and each is surrounded by a cluster of smaller, undifferentiated mesoderm cells. Each MP develops into a bundle of muscle fibers by a cycle of fusion and division. The individual mesoderm cells surrounding each MP fuse with it starting at about 60%. At the same time, the large MP begins to divide into smaller muscle fibers. PMID- 4043527 TI - Developmental changes in the responses of rat chromaffin cells to neuronotrophic and neurite-promoting factors. AB - This study describes the survival and neurite outgrowth behaviors of cultured adrenal medullary (chromaffin) cells obtained from postnatal rats 1 day (D1) to 100 days (D100) old in response to nerve growth factor (NGF), chick eye ciliary neuronotrophic factor (CNTF), and laminin. In the absence of trophic factors the 4-day survival of cultured chromaffin cells (relative to the number of cells attached at 2 hr) increased from one-third of the cells at D1 to 40% at D8 and 90 100% at D16 and older stages. At saturating concentrations NGF increased cell survival at D8 by 90%, but failed to support all chromaffin cells present at 2 hr. In contrast, CNTF supported the survival of all cells at D8. At D1 NGF and CNTF had only a very small effect on survival during the 4-day culture period, although both factors clearly enhanced the numbers of surviving cells after 8 days. Either NGF or CNTF also elicited neurite outgrowth from rat chromaffin cells, which amounted to approximately 15-20% at D1 and D8 and subsequently decreased to about 5-8% at D30 and virtually zero at D100. At this last age both factors applied together clearly elicited neurites. Such a potentiating effect of NGF and CNTF was also seen at earlier postnatal ages. Laminin did not affect neurite growth at D30 in the absence of trophic factors, as already described for D8 rat chromaffin cells. In the presence of NGF, however, it increased neurite length and branching during a 4-day culture period and even enhanced neurite recruitment at later culture times. These data suggest that rat chromaffin cells undergo age-related changes in their responses to NGF and CNTF and that laminin modulates their neurite outgrowth behaviors in the presence of trophic factors. PMID- 4043528 TI - Inhibition of limb chondrogenesis by a Veratrum alkaloid: temporal specificity in vivo and in vitro. AB - It has been demonstrated that jervine, a steroidal alkaloid derived from plants of the genus Veratrum, exerts teratogenic effects in several animal species. Defects were restricted to structures which depend upon normal chondrogenesis for their development. Here we report studies of the temporal specificity of cellular sensitivity using limb bud mesenchyme cells obtained from Day 10 mouse embryos. These cells, when grown as high-density "spot" cultures, undergo chondrogenesis in vitro. Prior to differentiation, exposure of limb cell cultures to jervine suppressed subsequent accumulation of cartilage proteoglycans. Treatment after differentiation had no significant effect. Additionally, there was a genetic component to jervine sensitivity: C57BL/6J mice were sensitive, whereas NIH Swiss Webster mice were insensitive. This strain-dependent difference was observed both in vivo and in vitro, supporting the validity of limb mesenchyme spot cultures as a model for jervine-induced teratogenicity. Our studies indicate that jervine acts specifically during an early phase of the differentiation of mesenchyme into cartilage. It is likely that a specific stem cell population is the target tissue of this compound. PMID- 4043529 TI - Growth regulation of the interstitial cell population in hydra. II. A new mechanism for the homeostatic recovery of reduced interstitial cell populations. AB - The interstitial cells of hydra comprise a stem cell population, producing at least two classes of terminally differentiated cell types, nerve cells and nematocytes. Exposure to hydroxyurea (HU) results in selective depletion of interstitial cells from the tissue. The surviving cells subsequently recovered to normal levels, and the mechanisms involved in this repopulation were examined. Hydra were treated for varying times with HU such that interstitial cell numbers were reduced to 7 or 35% of normal. Subsequent growth of the epithelial and interstitial cell populations in these animals was monitored. The results indicate that the growth rates of these two cell types were only slightly different from untreated controls during the 4 weeks after HU exposure, implying that repopulation should not have occurred. However, recovery of the interstitial cell population was observed. Further analysis revealed that the interstitial cells in HU animals, unlike normal hydra, were not uniformly distributed in the body column, and were especially reduced in the budding region. In normal animals a constant fraction of the interstitial and epithelial cells are lost into buds. However, as a consequence of this nonuniform distribution a smaller fraction of the interstitial cells are displaced into HU buds, thereby retaining a higher proportion in the adult tissue. Calculations indicate that this mechanism of increased retention is of sufficient magnitude to account for 40-60% of the observed recovery after HU treatment. PMID- 4043530 TI - The characterization of three monkey kidney cell lines. AB - Three monkey kidney cell lines, Vero, GL-V3 and MA-104 were subjected to karyological analysis to determine their chromosomal stability and to confirm their species of origin. Although the lines were shown to be relatively stable throughout all of the passage levels that were tested, the species of origin of one of them was found to be different from that claimed by the originators. This finding was supported by data from isoenzyme studies. PMID- 4043531 TI - A rabies vaccine produced in a non-tumorigenic rabbit cell line. AB - From the trypsinized skin of a rabbit embryo, a fibroblastic cell line has been obtained (FEL cells). The primary seed lot has been established at 11th passage. The tests for tumorigenicity on nu/nu mice were negative (10(4) cell/animal) at passage level 11th and 50th. Cell growth and morphology were not altered when 100 passages were performed. FEL cells were tested for their susceptibility to rabies virus. The production of virus on FEL cells was investigated after infection by the P.V. rabies virus strain adapted to several cell types (bovine fetal kidney, Vero and BHK cells). For the evaluation of an experimental rabies vaccine produced with this substrate, FEL cells were compared to Vero cells. The synthesis of glycoprotein (EIA) and the immunogenicity (NIH test) were similar for the vaccines obtained with both cell systems. FEL cells could therefore be an alternative to Vero cells for the production of a cell culture inactivated rabies vaccine. PMID- 4043532 TI - Cell bank characterization for recombinant DNA mammalian cell lines. AB - Cell banks were created by controlled rate freezing of pooled cell suspensions. Each line was characterized for freedom from adventitious agents, identity and biological behavior in immunosuppressed animals. Pharmacopeal culture methods were employed to search for bacterial, fungal and mycoplasma contamination. Conditioned medium was inoculated into a battery of 6 cell lines to search for acute viral contamination. Recombinant cell lines were also examined for retroviruses by electron microscopy, reverse transcriptase assay, XC plaque assay, tritiated uridine labelling, chemical induction techniques, and co cultivation with three indicator cell lines. Further characterization was obtained from inoculation of 4 animal species in vivo, mouse antibody production test, and inoculation of immunosuppressed rodents. Finally, cytogenetic evaluation including banding methods and isoenzyme analysis were employed to verify cell bank identity. These methods have generated useful data concerning the identity, safety, and biological purity of recombinant DNA mammalian cell lines. PMID- 4043533 TI - Growth kinetics of hybridoma cells: (1) The effects of varying foetal calf serum levels. AB - The growth kinetics, i.e. growth rate, cell yield and antibody production, of two murine hybridoma cell lines have been studied in several commercial media at different FCS levels in static 25 cm2 flask cultures. Reduction of FCS levels from 10% to 5% did not affect significantly the antibody yield whereas at 2% and 1% FCS levels growth rate, cell and antibody yield were reduced significantly in all media. Considerable differences were noted in the maximum cell populations obtained in the different media, with IMDM producing the highest cell and antibody yields; IMDM greater than HiGem greater than DME greater than RPMI. The cell lines did not grow in the absence of FCS but did grow in the presence of basal medium supplemented with insulin and transferrin at 10 mg per L. Both cell lines were stable during several months' passage in this medium. A supplement containing human albumin or BSA at 1 g per L combined with the insulin and transferrin (10 mg per L) could replace 1% FCS in DME without significantly affecting the cell yields of B6. PMID- 4043534 TI - Parvovirus serologically related to the minute virus of mice (MVM) as contaminant of BHK 21 cl. 13 suspension cells. AB - From BHK 21 cl. 13 suspensions cells we have isolated a virus serologically related to the Minute Virus of Mice (MVM); the same virus has been isolated from the same cells in U.K. in 1980. Besides isolating this virus from large scale cultures, we have also isolated it from many of the sublines stored in nitrogen we received at different times from different laboratories. At this time it is difficult to ascertain if the contamination originated from the serum or from other components of the medium; furthermore we do not know if many of the cells of our stock became contaminated in our laboratory or if they were already contaminated. PMID- 4043535 TI - Further investigations on serum ultrafiltrate as medium for tissue respiration in vitro. AB - Serum ultrafiltrate was shown to be able to sustain in vitro the oxygen consumption of various tissue slices, attaining values very close to those reached in vivo. Serum ultrafiltrate also exerted its stimulating effect on homogenate, and maintained this activity for some time, after dilution, after lyophilization and after boiling; finally it was not species-specific. Serum ultrafiltrate was also more efficient than Eagle's Minimum Essential Medium in supporting tissue respiration. Preliminary data, obtained from gel fractionating serum ultrafiltrate, suggested that the metabolic activity should be ascribed to a sum of small single effects due to the single fractions of serum ultrafiltrate. PMID- 4043536 TI - Factors affecting the production of plasminogen activator in cultures of normal fibroblasts. AB - Plasminogen activator (PA) is a serine protease with a proven medical application as a fibrinolytic drug. PA is a normal constituent of animal tissues and is found in low concentration 1-10 U/ml in the supernatant of various cells in culture. We found that certain strains of untransformed human diploid fibroblasts can be adapted to produce PA at levels of 100 U/ml or more by culture with specific combinations of serum and coated substrates. Once the cells are adapted, they continue to produce the enzyme in a medium devoid of serum in which cell proliferation is minimal. The time course of enzyme production revealed that its formation is controlled by negative feedback and stops when its level in the medium reaches a critical concentration. However on removal of the enzyme by continuously replacing the medium, the cells continue to produce enzyme at a constant rate for a period of several weeks. Possible biotechnological configurations for large scale production of this enzyme are now under study. The PA purified from the spent medium of these cells was identified as tissue type activator similar to the melanoma type PA. PMID- 4043537 TI - Monoclonal ELISA for the determination of BNYV-virus. AB - Monoclonal antibodies have been developed against the BNYV-virus (beet-necrotic yellow-vein) which causes the rhizomania disease in sugar beet (Beta vulgaris). The B103 hybridoma produced predominantly IgG2a at greater than 100 micrograms/ml. IgM-production could not, however, be ruled out. In a polyclonal monoclonal indirect sandwich ELISA, the B103-antibody bound to BNYVV of Austrian, German, French and Bulgarian origin at a sensitivity of 1 ng/ml or less. Comparison of sugar beet samples in ELISA and immuno-electronmicroscopy showed good correlation, demonstrating the good performance of B103 antibody for broad application in BNYVV diagnosis. PMID- 4043538 TI - RDB--a new product of plant origin for cell culture dispersion. AB - RDB is a crude preparation extracted from a plant source. It is a very potent agent for dispersion of monolayer cell cultures as well as for the preparation of primary cell suspensions. It was found to be most effective in dispersing a wide range of animal and mosquito cells and dissociating neuronal and muscular tissue for primary cell cultures. RDB was also found to be useful for preparation of primary culture for chick embryo fibroblasts. After treatment with RDB cell viability was found to be 98% as compared to 85% in trypsin treated monolayer cultures. Routine dispersion of monolayer cultures with RDB does not have any negative effect on confluency of the newly split cultures. RDB was found to have no adverse effects on viral replication and plating efficiency of Rift Valley Fever Virus, Sindbis Virus and West Nile Virus. PMID- 4043539 TI - Structural and immunogenic characteristics of rabies immunosomes. AB - Rabies immunosomes are prepared by the anchorage of glycoprotein molecules to preformed liposomes. Virosomes are associations of glycoprotein molecules with viral or non viral lipids. Virosomes can be obtained spontaneously after removal of the detergent used for lipids solubilization. Under the electron microscope immunosomes look like homogenous spherical vesicles (50-60 nm) evenly covered with spikes, although glycoprotein molecule orientation in virosomes is not yet clearly established. In addition, the size of virosomes is very heterogeneous. When glycoprotein molecules are in immunosome form, their accessibility to a lectin (WGA) is identical to that of the purified virus. Under the same conditions with virosomes accessibility is weaker. Protection induced in mice is ten to twenty fold higher with rabies immunosomes than with purified glycoprotein or virosomes. The results presented here and previous reports (10) show that immunosomes have structural and immunogen characteristics closer to those of purified and inactivated virus than does any other form of glycoprotein lipids association. PMID- 4043540 TI - Production and growth of hybridomas secreting monoclonal antibodies to human thyroid stimulating hormone. AB - Female Balb/c mice were immunized with human thyroid stimulating hormone (hTSH). The spleen cells of responding mice were used in a cell fusion with NS1 mouse myeloma cells to define 27 stable anti-hTSH hybridomas. The antibody-secreting cell lines, designated SY/T8/1-6, were characterized and three were found to be completely specific for h-TSH while the other three showed some cross reactivity with LH and hCG. Six of the monoclonal antibodies have been well characterized and their parent hybridomas isolated and banked at -196 degrees C for future studies. The hybridomas have been raised from liquid nitrogen and recultured in RPMI 1640 medium. Progress is being made in the investigation of the growth characteristics of these hybridoma cell lines. PMID- 4043541 TI - The effects of econazole on the growth of murine myeloma cells and its use in hybridoma production. AB - The effect of econazole, an antifungal agent, on the stability of NS1/Ag4 myeloma cells in culture was investigated with the view to its use in the control of fungal contamination in lymphocyte hybridoma monoclonal antibody production. The recommended dose of 1 microgram/ml was found to reduce cell numbers, viability and survival, and to effect dramatic dose related changes in DNA synthesis in the NS1 myeloma line and hence econazole is not suitable as an added antifungal agent in monoclonal antibody production using NS1 cells and their derived hybridomas. PMID- 4043542 TI - Some characteristics of the ICCe-1, a new simian embryo cell line. AB - A new simian embryo cell line has been established from a Cercopithecus male whole embryo. The resultant predominant fibroblast-like cell population has been frozen in convenient quantities and characterized for use in biological research as well as in theoretical and practical virological purposes. The cell line was designated ICCe-1 (Institute Cantacuzino Cercopithecus embryo-1). PMID- 4043543 TI - Use of plasma protein fractions as serum substitutes for in vitro cell culture. AB - Fractions produced during routine production of human plasma protein concentrates using cold ethanol precipitation have been tested for their ability to support animal cell growth in vitro. A mouse-mouse hybridoma cell line, ES-6, which secretes a monoclonal antibody (mab) to human group A red blood cell antigen, has been used as a model. Fraction 4-1 protein has been found to be effective at 0.5 1.0 g/l in RPMI 1640 and has supported growth of ES-6 for 18 months, both growth and mab. production being comparable with that achieved in 10% foetal calf serum. Fraction 4-1 protein has been shown to contain albumin, transferrin, alpha-1 antitrypsin and immunoglobulin. It is reported to be a source of somatomedin C. The immunoglobulin content can be reduced. Other mouse and rat hybridomas, human mab. producing lymphoblastoid cells, Namalva and HEP-2 cells have grown well in medium supplemented with Fraction 4-1 protein. PMID- 4043544 TI - Growth kinetics of hybridoma cells: (2) The effects of varying energy source concentrations. AB - Commercial media used for the growth of hybridoma cells contain different glucose concentrations. We have attempted to establish the optimal levels of glucose required for maximum hybridoma cell yields by studying the energy source metabolism of two murine hybridoma cell lines in several commercial media in static 25 cm2 flask cultures. The glucose and lactate quotients and growth yields from glucose of the two cell lines were similar in all media. Glucose limited growth in DME containing lg/L. Glucose supplementation to 2g/L in DME significantly increased cell and antibody yields. When fructose was used as a substitute for glucose the fructose quotient of one cell line was found to be similar to its glucose quotient whereas that of the other cell line was significantly reduced compared to its glucose quotient. PMID- 4043545 TI - A screening method to develop serum-free culture media for adherent cell lines. AB - A screening method was established to develop chemically defined, serum-free culture media for human adherent cell lines. It indicates within 2-6 months whether a certain cell line is suited for routine cultivation under serum-free conditions, and which medium supplements and surface coatings of the culture vessels the cells need for minimal demand. This method was tested with the human cell lines Bowes melanoma and prostate carcinoma 3 (PC 3). PMID- 4043546 TI - The effects of early handling on latent inhibition in male and female rats. AB - Latent inhibition (LI) is a behavioral paradigm in which repeated exposure to stimuli not followed by meaningful consequences renders these stimuli ineffective for subsequent learning. The development of LI is considered to reflect learning not to attend to, ignore, or tune out irrelevant stimuli. The present study investigated the differences in the development of LI between handled and nonhandled males and females. Infantile handled (Days 1-22) and nonhandled, male and female Wistar rats were tested in maturity in the LI paradigm. The LI procedure consisted of two stages: pre-exposure, where animals received 60 presentations of the to-be-conditioned stimulus (tone) and test, where the animals acquired a two-way active avoidance response with the tone serving as the warning signal. Handled animals reached higher percentage of avoidance responses as compared with nonhandled animals. Latent inhibition was obtained in both the handled and the nonhandled females, but only the handled males showed the LI effect. Nonhandled males failed to develop LI. The results indicate that the effects of handling are evident in learning tasks that do not involve motivational-emotional variables, i.e., learning to ignore irrelevant stimuli; handling differentially affects males and females, with a much greater impact on males and the nonhandling procedure has significant deleterious consequences on adult behavior. PMID- 4043547 TI - Effects of early experience on the development of filial preferences in the domestic chick. AB - Factors affecting the development of filial preferences in chicks were investigated. Four groups of chicks were hatched and maintained in darkness. When the chicks were 20-hr old, three of these groups were exposed to an overhead light ("primed") for .5 h. When 24-hr old, all groups were placed in running wheels for 2 hr. While in the wheels one group was exposed to a visually complex pattern, one group to diffuse overhead light, and the remaining two groups (one primed and one not primed) were in darkness. All chicks were then returned to a dark incubator until their preference for a red box or a stuffed jungle fowl was measured in a simultaneous choice test either 2 hr (Test I) or 24 hr (Test II) later. At Test I the chicks which had been exposed to the complex visual pattern showed a significant preference for the fowl. Chicks in the other groups showed no preference. At Test II all groups showed a significant preference for the fowl. The results of a second experiment suggested that the later emerging preference was related to the chicks experience in the running wheel. It was concluded that the preference for the fowl will develop in entirely dark-reared chicks that are allowed a period of time in a running wheel, but that this preference will appear earlier in chicks which have had experience of a complex visual pattern. PMID- 4043548 TI - Development of maternal behaviors in prepubertal rats at three ages: age characteristic patterns of responses. AB - Individual 18-, 24-, or 30-day-old male and female Wistar prepubertal rats (juveniles) were continuously exposed to 3-8-day old pups in order to determine developmental differences in the expression of maternal and other behaviors during the process of sensitization. The results that emerged from this study are as follows: Maternal behaviors are neither consistent nor integrated in their expression prepubertally; exposure to pups facilitates the emergence of some maternal behaviors in juveniles more easily than others, e.g., retrieving and anogenital licking more than ventral crouching or nestbuilding; there are age related differences in the expression of different maternal behaviors, e.g., 24 day-olds retrieve more than at other ages; in our strain, few, if any, gender differences are apparent in the expression of maternal behaviors prepubertally; juvenile play behaviors (charge, pounce) are related to retrieving behavior in the context of exposure to pups. Overall, the results suggest that maternal behaviors are distinct developmentally and probably involve different mechanisms in prepubertal animals. PMID- 4043549 TI - Individual differences in mood in early childhood: their relation to gender and neonatal sex steroids. AB - Predominant mood states were assessed for 104 children via 24-hr mother diaries during the first 2 years of life. Consistent sex differences were found across ages and across cohorts: boys were more often reported to be in a happy/excited mood, girls in a quiet/calm mood. The sexes did not differ in the frequency of negative moods (including crying), however. Scores for happy/excited and quiet/calm mood states were quite stable across the ages sampled: 6, 9, 12, 18, and 26 months. These stabilities were generally greater for boys. Negative moods showed only borderline stability. Relationships between the mood scores and five sex-steroid hormones (progesterone, androstenedione, testosterone, estrone, and estradiol), assayed from umbilical cord blood at the time of the children's birth, were assessed. For boys small, but significant, positive relationships were found between happy/excited moods and androstenedione, estrone, and progesterone. Correlations of opposite sign were found between these hormones and boys' scores for quiet/calm mood. For girls, the correlations were low and insignificant, but generally of opposite sign from those found for boys, and a number of hormones showed significant sex-by-hormone interactions in their relation to children's mood scores. The implication of these findings for the understanding of sex differences is discussed. Also discussed are the problems of interpretation posed by the intercorrelations among hormones when hormone scores are used for prediction of aspects of later development. PMID- 4043550 TI - The effects of rearing environment on pup development. AB - Norway rats were reared either in a standard laboratory cage or in a nest constructed by the dam from newspaper strips. Growth, thermoregulatory ability, and adrenal, gonad, adipose tissue, and brain weights were measured at weaning on Day 21 postpartum. While there was no difference in growth, nest-reared animals had lower body temperatures, but could thermoregulate as well as cage-reared animals. Nest-reared animals also had relatively smaller adrenals and less brown adipose tissue. Gonad and brain weights were similar. An interesting finding was that males and females were differentially affected by the nest-rearing. Differences between cage- and nest-reared animals were more evident in females, and thermoregulatory ability was more closely associated with the quality of the nest during the first 10 days than body weight in females. For males, body weight was more important. These latter data are discussed in relation to differential interaction between the dam and male and female pups. PMID- 4043551 TI - Adrenalectomy in the developing rat: does it cause reduced or increased brain myelination? AB - We have previously demonstrated increased myelination in adult rats that were adrenalectomized (ADX) neonatally. However, Preston and McMorris (1984) recently reported reduced myelination at Day 21 or 22 in day 14 ADX animals. The present experiment attempted to replicate Preston and McMorris' study to determine whether early adrenalectomy might be producing a transient hypomyelination prior to the hypermyelination observed at later time points. We were unable to duplicate the exact protocol of Preston and McMorris (which involved weaning at Day 18 with administration of saline and glucose drinking solutions) because of 100% mortality of our ADX rats by Day 20. However, using our standard mineralocorticoid replacement therapy which allowed the animals to remain with their mothers, all of the ADX rats survived, and we were able to assess myelination in these animals by means of standard biochemical methods. All measures showed absolutely no reduction in myelination in ADX rats compared with sham-operated controls. The discrepancy between the present results and those of Preston and McMorris are attributed, at least in part, to the early weaning procedure used by these investigators. PMID- 4043552 TI - Mediation of passive avoidance learning by nicotinic hippocampo-entorhinal components in young rats. AB - Young rats, 11, 16, and 20 days of age, received bilateral injections of three antinicotinic agents into the posteroventral hippocampo-subiculo-entorhinal area, and were trained to learn a cool-draft-stimulus, passive-avoidance task shortly after (17 min). Gallamine triethiodide had no action at low doses and provoked convulsions at higher concentrations. Pempidine tartrate produced age- and dose dependent impairments of the passive avoidance, and was much more effective in younger groups (11 and 16 days) than at 20 days. alpha-bungarotoxin also induced dose-dependent deficits. These results, together with the mecamylamine-induced deficits already reported, suggest that nicotinic cholinergic synapses located in the posteroventral part of the hippocampal complex play a role in passive avoidance learning in the young rat as soon as this type of conditioning is possible, but become relatively less important at older ages, when muscarinic mechanisms also become involved. PMID- 4043553 TI - The effect of maternal diabetes on trace element status and fetal development in the rat. AB - Despite improvements in prenatal care, there is a high incidence of congenital malformations in diabetic pregnancies. Not only is the diabetic patient characterized by a disorder of total fuel metabolism, but abnormal trace element metabolism occurs as well. In the present study, maternal and fetal zinc (Zn), copper (Cu), manganese (Mn), iron (Fe), magnesium (Mg), and calcium (Ca) status has been studied in Sprague-Dawley (SD) and Wistar rats. In addition, the effect of maternal diabetes on fetal development was also investigated. Rats were injected 27 days before mating with streptozocin (STZ, 45 mg/kg) in citrate buffer. On day 20 of gestation, litters were taken by cesarean section. Fetuses from diabetic dams weighed less, and had shorter crown-rump lengths and larger placentas than fetuses from controls. Evaluation of fetal skeletal development revealed fewer calcified sternal sites, anterior phalanges and caudal vertebrae, and an increased frequency of malformations in fetuses of diabetic dams. In dams, diabetics had larger adrenals, kidneys, and liver, and smaller thymus. Abnormal trace element metabolism was evident in diabetic dams and their fetuses. Mn was elevated in maternal liver, kidney and placenta of diabetic animals as well as in fetal liver of pups from diabetic dams. Maternal Cu and Zn levels were also higher in the liver and kidney of diabetic rats. In contrast, fetal liver Zn from fetuses of diabetic mothers was significantly decreased when compared with controls. These results suggest that diabetes may have induced fetal Zn deficiency. If this deficiency is present during embryogenesis/organogenesis, this could be one of the mechanisms of the teratogenicity of the diabetic state. PMID- 4043554 TI - The influence of body fat distribution on the incidence of diabetes mellitus. 13.5 years of follow-up of the participants in the study of men born in 1913. AB - In a prospective study of risk factors for ischemic heart disease, 792 54-yr-old men selected by year of birth (1913) and residence in Goteborg, Sweden, agreed to attend for questioning and a number of anthropometric and other measurements in 1967. Thirteen and one-half years later, these baseline findings were reviewed in relation to the number of men who had subsequently developed diabetes mellitus. This analysis focused on the importance of abdominal adipose tissue distribution, measured as the waist-to-hip circumference ratio, as a predictor for development of diabetes. Even when the confounding effect of body mass index, as a measure of the total body fat mass, was accounted for, the waist-to-hip ratio was positively and significantly associated with the risk for diabetes. These results from a prospective study strongly support previous cross-sectional findings indicating that not only the degree of obesity but also the localization of fat is a risk factor for diabetes. PMID- 4043555 TI - Reduced insulin sensitivity in nondiabetic, HLA-identical siblings of insulin dependent diabetic subjects. AB - Nondiabetic, HLA-identical siblings of insulin-dependent diabetic subjects have an increased risk of developing diabetes. Since insulin resistance is present in newly diagnosed diabetic subjects, we studied 12 HLA-identical siblings to determine whether they have impaired insulin sensitivity. Each sibling was carefully matched for age, sex, and body weight to a control from a nondiabetic family. The insulin sensitivity index (SI) was determined after an intravenous glucose tolerance test (IVGTT) using the minimal model of insulin kinetics. The insulin sensitivity index was significantly lower in the HLA-identical siblings compared with their matched controls. PMID- 4043556 TI - Pyruvate dehydrogenase activity in cardiac mitochondria from genetically diabetic mice. AB - Pyruvate dehydrogenase (PDH) was studied in isolated heart mitochondria from genetically diabetic mice (C57BL/KsJ db/db) with progressive cardiomyopathy. Both the basal activity (active enzyme) and the total activity (the sum of active and inactive enzyme) were determined. In mitochondrial extracts from 8-18-wk-old db/db mice, there was a 73% decrease of basal activity accompanied by a 38% decrease of total activity as compared with controls. The lower basal activity at 8 wk of age suggests an increased conversion of the enzyme into the phosphorylated (inactive) form. Evidence is also given that the conversion of inactive (phosphorylated) enzyme into active (dephosphorylated) enzyme is inhibited in cardiac mitochondria prepared from 8-wk and older db/db mice. These changes coincide with the onset of defective oxidative metabolism and can explain the depressed pyruvate oxidation reported previously. PMID- 4043557 TI - Tissue-specific antibodies against the fibroblast insulin receptor in a patient with lupus nephritis and hypoglycemia. AB - We recently reported that the serum from a patient with lupus nephritis, insulin resistance, and hypoglycemia contains multiple populations of antibodies directed at the human insulin receptor. In the present study, we found a subpopulation of antibodies (eluted from a protein A-Sepharose affinity column at pH 4.3) directed at the human fibroblast insulin receptor. When tested against human placental membranes, IM-9 lymphocytes, circulating monocytes and erythrocytes, and isolated adipocytes, the antibody subpopulation did not compete with 125I-insulin for binding to its receptor. In contrast, the antibody subpopulation competed with 125I-insulin for binding to the human fibroblast insulin receptor. This antibody subpopulation stimulated [3H]alpha-aminoisobutyric acid [( 3H]AIB) uptake to these cells. Unlike the effect of insulin, however, this regulation of transport was not antagonized by a mouse monoclonal antibody to the human insulin receptor that inhibits 125I-insulin binding. These studies indicate, therefore, that a tissue-specific antibody subpopulation can occur spontaneously in patients with antibodies to the human insulin receptor. Furthermore, they indicate the presence of anti-insulin receptor autoantibodies specifically directed against a tissue that is not primarily involved in glucose metabolism. PMID- 4043558 TI - Gastric acid and pancreatic polypeptide responses to sham feeding are impaired in diabetic subjects with autonomic neuropathy. AB - To assess the relationship between cardiac and extra-cardiac dysfunction in diabetic autonomic neuropathy, the gastric acid output and the pancreatic polypeptide (hPP) secretion in response to sham feeding were evaluated in diabetic patients with (group 1) and without (group 2) cardiac autonomic neuropathy (CAN), and in normal subjects (group 3). All patients assigned to the group with CAN exhibited an impaired beat-to-beat heart rate variation during deep breathing. The basal gastric acid output was comparable in the three groups (1.3 +/- 0.5, 2.8 +/- 1.5, and 3.9 +/- 1.5 mmol/h, respectively). In contrast, the gastric acid output stimulated by sham feeding was significantly lower in patients with CAN (5.3 +/- 1.3 mmol/h) than in diabetic subjects without CAN (14.0 +/- 3.5 mmol/h; P less than 0.01) and in controls (10.9 +/- 3.1; P less than 0.05). The maximal gastric acid secretion capacity, determined after pentagastrin injection, was similar in all patients. Mean basal hPP concentrations were comparable in the three groups (185 +/- 53 pg/ml, 131 +/- 29 pg/ml, and 116 +/- 19 pg/ml). In the controls and diabetic subjects without CAN, a significant mean 60% increase of the hPP levels above basal values was observed during sham feeding. In contrast, no significant hPP response occurred in the group with CAN. These data suggest that diabetic CAN is associated with dysfunctions of the vagal pathways controlling the gastric acid output and the hPP secretion. Moreover, the results demonstrate a strong association between cardiac autonomic neuropathy and gastric vagal neuropathy (P less than 0.001). PMID- 4043559 TI - Spontaneous activity of primary afferent neurons in diabetic BB/Wistar rats. A possible mechanism of chronic diabetic neuropathic pain. AB - The mechanism of painful diabetic neuropathy remains unknown. Spontaneous activity in nociceptive primary afferents has been implicated in the genesis of chronic pain due to peripheral nerve injury, and diabetic axonopathy shares some histologic features with traumatic neuropathy. We hypothesized that spontaneous hyperactivity of nociceptive neurons might represent the neurophysiologic mechanism of diabetic neuropathic pain. To test this, we examined the spontaneous activity of primary afferent axons from diabetic BB/Wistar and normal Wistar rat saphenous nerves isolated from central and peripheral connections. Microfilament recordings from diabetic nerves showed a significantly higher incidence of spontaneous discharges in comparison to normal nerves. Furthermore, this spontaneous hyperactivity occurred almost exclusively in potentially nociceptive C-fibers. We conclude that in the diabetic BB/Wistar rat, spontaneous impulses are generated in potential nociceptive primary afferent neurons, and that this may represent the mechanism of chronic diabetic neuropathic pain. PMID- 4043560 TI - Glucagon, secretin and vasoactive intestinal polypeptide immunoreactivities in rat gut after jejuno-ileal bypass and resection. AB - Jejuno-ileal bypass (JIB) and resection are associated with hyperplastic and other changes in residual functional gut. In studies on endocrine changes, circulating hormone levels are usually measured. In this study with Sprague Dawley rats, glucagon, secretin and vasoactive intestinal polypeptide (VIP), immunoreactivities were measured in extracts of gut tissues including formerly adjacent segments of functional and bypassed jejunum and ileum. Young adult (200 220 g) and mature (404-440 g) rats received greater than 90% JIB. Though slight differences were observed in the response of the young and old rats to the operations, and between the effects of JIB and resection, the results do not indicate major involvement of secretin, VIP or gut glucagon-like immunoreactivity in the effects of surgery. Changes include increased immunoreactivity of secretin in the upper and of VIP in the lower functional gut following JIB. N-terminal-to central glucagon immunoreactivity in the functional ileum did not change substantially after operations, but was significantly lower in the non-functional than functional ileum after bypass. Plasma levels of this immunoreactivity were higher following operations and highest following resection. PMID- 4043561 TI - Changes in motility after jejunal and ileal resection: electromyographic study in rats. AB - The aim of this work was to compare the effects of massive jejunal and ileal resections on intestinal motility using an electromyographic technique. Male Wistar rats were used: in the first group a massive jejunal resection was performed, conserving a 7-cm segment after the ligament of Treitz; the rats of the second group underwent an ileal resection, preserving 7 cm of the terminal ileum. Motility was studied at the 10th and 30th postoperative days by means of electrodes implanted throughout the remaining bowel and was expressed by the pattern of recurrence of the migrating myoelectric complex (MMC). In a fasting state, in both transected and resected animals at the 10th postoperative day, the gradient in the duration of MMC along the intestine still existed. However, on the 30th postoperative day, in animals with jejunal resection only, there was an adaptive process: the duration of MMC in the remaining jejunum was significantly increased to the duration in the ileum. After the end of the postprandial inhibition of the appearance of the MMC, on the 10th postoperative day there was a significant decrease in the duration of MMC in the ileum in both types of resection, compared to the controls. However, on the 30th postoperative day, the duration of MMC returned to its control value. In conclusion, jejunal resection seems to induce more important adaptive processes in intestinal motility than does ileal resection. The different results are discussed. PMID- 4043562 TI - Endoscopic pancreatography in chronic pancreatitis of the tropics. AB - The ERCP findings in 13 patients with chronic pancreatitis of the tropics are reported. 7 of the patients had pancreatic calculi on plain film of abdomen and 6 had no calcification. The changes observed in the pancreatograms were tortuosity, dilatation, stenosis, obstruction, cyst formation and presence of calculi in the main pancreatic ducts and their finer branches. The calcific variety showed a greater degree of ductal derangement compared to the non-calcific variety. The common bile duct was normal in all the patients. The pancreatographic changes observed are similar to those described in the alcoholic and other varieties of chronic pancreatitis. PMID- 4043563 TI - Exocrine pancreatic function in hepatosplenic schistosomiasis in the Sudan. AB - Exocrine pancreatic function was studied in 36 patients with hepatosplenic schistosomiasis and 31 control subjects. The secretin test and the Lundh test meal were used to assess exocrine pancreas function. Patients with hepatosplenic schistosomiasis had a significantly lower bicarbonate concentration, less than 90 mmol/l in duodenal aspirate, than the control group (p less than 0.001). There were statistically insignificant differences in the volume of the duodenal aspirate after the secretin test and in the mean tryptic activity after the Lundh test meal between patients and controls. We conclude that exocrine pancreatic function is impaired with regard to bicarbonate secretion in hepatosplenic schistosomiasis. PMID- 4043564 TI - Plasma cholecystokinin levels in patients with chronic pancreatitis. AB - Using a sensitive and specific radioimmunoassay for cholecystokinin (CCK) we have measured plasma CCK levels in patients with and without chronic pancreatitis. All patients suffered from steatorrhea. The basal plasma values in patients with chronic pancreatitis (n = 10) were significantly higher compared with a control group of 40 normal subjects. After ingestion of a test meal peak plasma levels of CCK were significantly higher than in controls, but the integrated CCK release did not differ from the normal subjects. The findings indicate a close relationship between plasma CCK concentration and exocrine pancreatic function. PMID- 4043565 TI - Tuberculous oesophagopulmonary communication: effectiveness of antituberculous chemotherapy. A case report and review of literature. AB - A patient with tuberculous oesophagopulmonary communication diagnosed by oesophagography and confirmed by endoscopy was successfully treated by medical means: a tuberculous aetiology was suggested by the detection of tubercle bacilli in the gastric washings and on culture. On reviewing the medical literature, successful results were reported in 3 adults and 2 children. PMID- 4043566 TI - Reduced intestinal protein loss in Crohn's disease after lymphovenous anastomosis. AB - In a 27-year-old patient suffering from Crohn's disease covering nearly the entire small intestine, the major problem was a marked protein-losing enteropathy which required long-term intravenous replacement. Accidentally, we disclosed a dilated thoracic duct with incompetent valves and stenosis at the junction into the subclavian vein in this patient. To reduce the intestinal protein loss, an anastomosis was performed between the thoracic duct and the internal jugular vein. Subsequently the intestinal protein loss dropped from 40 to 26% and replacement of proteins could be reduced. The patient was observed for 4 years postoperatively and the therapeutic effect continued. Besides this therapeutic aspect, the present case gives cause to consider the possible role of the lymphatics in the pathogenesis of Crohn's disease. PMID- 4043567 TI - Effect of acute and chronic oral administration of ethanol on canine exocrine pancreatic secretion. AB - The action of an intragastric injection of ethanol (1.0-1.5 g/kg), either in the fasting animal or with a solid meal, has been studied in two groups of 4 conscious dogs provided with gastric and duodenal Thomas cannulae: one group of 'alcoholic dogs' (AD) had been given 2 g/kg/day ethanol over a period of 24 months, the second group of 'nonalcoholic dogs' (NA) had been given water as control. In NA, intragastric ethanol inhibited water and bicarbonate secretions, alcohol being given in the fasting animal or with a meal. In AD: (a) the nonstimulated output of water and bicarbonate, and to a lesser extent of protein, was decreased compared to NA, protein concentration being increased; (b) the bicarbonate response to a meal without ethanol was decreased, and (c) the most interesting finding is that in AD, the inhibitory action of intragastric ethanol as observed in NA, disappeared and was even replaced by a stimulation of water, bicarbonate and protein secretions. The disappearance in AD of alcohol-induced mechanisms inhibiting pancreatic secretion had already been found with other experimental protocols and involves muscarinic receptors. Inhibition of water and bicarbonate secretions remains unexplained. PMID- 4043568 TI - Toxic products in hemorrhagic ascitic fluid generated during experimental acute hemorrhagic pancreatitis in dogs and a treatment which reduces their effect. AB - Toxic substances produced in hemorrhagic ascitic fluid during experimental hemorrhagic pancreatitis in dogs were investigated. An average of 394 ml of ascitic fluid was produced within 5 h after the induction of acute pancreatitis by intraductal injection of a mixture of autologous bile and trypsin. Hemorrhagic ascitic fluid was collected under sterile conditions, which was confirmed by aerobic and anaerobic culture and a Limulus test. The sterile fluid was injected intraperitoneally into mice in doses of 2 and 3 ml, and the mortality rate 72 h after injection was 66.0 and 88.4%, respectively. It contained high concentrations of pancreatic enzymes, including trypsin and esterase activity, as well as bradykinin, histamine and prostaglandin. Autopsy and histological examination of mice revealed shock with lung damage. The results suggest that hemorrhagic ascitic fluid produced in pancreatitis may be an important factor for early deaths in acute pancreatitis. When a new synthetic antiprotease (nafamstat mesilate) in a dosage of 0.2 mg was mixed with 1 ml of ascitic fluid, trypsin was not detectable, and bradykinin was reduced 1.0 ng/ml from 8.0 ng/ml, while esterase activity decreased to one tenth of its previous activity. The mortality following injection of the solution decreased to 26.7 and 80.6%, respectively. These results indicate that peritoneal lavage with a solution containing antiprotease may be an effective treatment for hemorrhagic acute pancreatitis. PMID- 4043569 TI - EPC. European Pancreatic Club. XVIIth meeting, Manchester, September 22-25, 1985. Abstracts. PMID- 4043570 TI - Neonatal auditory brain stem responses from ipsilateral and contralateral recording montages. AB - Ipsilateral and contralateral auditory brain stem responses were recorded from both ears of 10 neonates between 37 and 43 weeks from conception with normal auditory brain stem function. The most prominent component of the contralateral response was a forehead positive deflection occurring 0.3 millisecond before the ipsilateral wave III followed by two forehead negative waves, the latter present at the same latency as the ipsilateral wave V. The amplitude of the contralateral response was small: at 30 dB nHL only 7 of the 20 ears showed clear responses from this montage. The morphology of the neonatal contralateral response is thus considerably different than the ipsilateral, unlike the adult. A neonate could be mistakenly diagnosed as hearing impaired or neurologically involved if the interpretation is based on the contralateral recording. PMID- 4043571 TI - Hearing loss in the elderly: an epidemiologic study of the Framingham Heart Study Cohort. AB - This study used epidemiologic methods to examine hearing loss in the elderly. The Framingham Heart Study Cohort was the reference population. The participants were 935 men and 1358 women, aged 57 to 89 years. Using a conservative definition of hearing loss as threshold levels greater than 20 dB above audiometric zero for at least one frequency from 0.5 to 4 kHz, the prevalence was estimated to be 83%. The majority of cases displayed a sensorineural hearing loss. There were no statistically significant differences by sex at 1 kHz and below. Women had significantly better hearing than men at 2 kHz and above. A multivariate model was constructed to determine which variables had a significant impact upon hearing loss. Under the model, age, sex, illness, family history of hearing loss, Meniere's disease, and noise exposure were significant population risk factors. Age was by far the most critical risk factor. PMID- 4043572 TI - Older persons' performance on auditory, visual, and auditory-visual presentations of the Edgerton and Danhauer Nonsense Syllable Test. AB - The speech sound discrimination abilities of 15 normal-hearing and 15 sensorineural hearing-impaired subjects between 55 and 65 years of age were assessed using videotaped presentations of the Nonsense Syllable Test (NST). Stimuli were presented in auditory (A), visual (V), and auditory-visual (AV) modes. All subjects received the stimuli in two trials for each presentation mode; hearing-impaired subjects were unaided for the first, and wore their own hearing aids for the second. Responses were transcribed phonemically and were scored by the phoneme method. Intra- and interjudge reliability was greater than 90%. Mean phoneme discrimination scores were plotted for each group across the three presentation modes. The results revealed that: both groups' performance improved from V to A to AV modes, but differences were apparent in the amount of increase across modes within each group; the NST differentiated between groups in the A and AV modes, but not in the V mode; the NST identified "poor" speechreaders in each group under both V and AV conditions; and consonant errors in the V mode formed seven homophenous categories based on place of articulation. The NST can be a useful screening test in auditory rehabilitation to distinguish those hearing-impaired persons who naturally take advantage of visual cues from those who do not. PMID- 4043573 TI - Comparison of monaural and binaural hearing aid use on a trial period basis. AB - Thirty hearing-impaired patients compared monaural and binaural hearing aid use for a period of 4 weeks. Most of them preferred binaural hearing aids in quiet situations, but monaural hearing aids in noisy environments. Follow-up at 6 months revealed that 17 had purchased monaural hearing aids, 8 had purchased binaural hearing aids. PMID- 4043574 TI - Cordless telephones and acoustic trauma: a case study. AB - Cordless telephones have been reported to cause irreversible damage to the ear due to acoustic trauma. The present case study reports an unusual audiometric configuration associated with direct exposure to the ring from a cordless phone. Although pure-tone sensitivity was only moderately affected, speech understanding was severely compromised. PMID- 4043575 TI - Influence of temperature on the output of a mechanical coupler. AB - This research determined the influence of temperature on the output of two Bruel and Kjaer 4930 mechanical couplers using a Radioear B-71, B-72, and a Pracitronic KH 70 bone vibrator. When the temperature of the mechanical couplers was varied from 17 degrees C (62.6 degrees F) to 29 degrees C (84.2 degrees F) in steps of 3 degrees C (5.4 degrees F) and the bone vibrators had a constant temperature, the output of each mechanical coupler systematically decreased as its temperature increased for each bone vibrator type. The largest output differences for both couplers and each vibrator occurred at 4000 Hz. The average of these differences across the couplers and vibrators was 6.6 dB higher at 17 degrees C than at 29 degrees C which dB/3.6 degrees F). When the temperature of the bone vibrators was 17 and 29 degrees C and the mechanical couplers were maintained at a constant temperature, there were little or no differences in the output of the mechanical couplers. The temperature of a mechanical coupler rather than that of the bone vibrator is a critical variable in bone conduction calibration. Mechanical coupler temperature-dependent output coefficients were determined for use in bone conduction calibration from 250 to 4000 Hz for all three bone vibrator types and at 6000 and 8000 Hz for the KH 70. PMID- 4043576 TI - Self-assessment of communication skills: toward the development of a new speech audiometric tool. AB - This investigation was carried out in an effort to characterize differences between groups of normal-hearing and hearing-impaired listeners on a speech perception test based on the theory of signal detection (TSD). TSD allows the quantification of two performance measures designed to evaluate listeners' ability to assess the accuracy of their own identifications and their level of confidence in the self-assessment task. It is hoped that these measures will provide a meaningful way to quantify communication skills beyond the percent correct word recognition score routinely measured in the audiology clinic. Nonparametric indices of self-assessment ability and confidence level, P(A) and B, respectively, were measured for ten normal-hearing and ten hearing-impaired subjects at two signal-to-noise ratios (S/N). In addition, percent correct word recognition scores (%C) were measured. Results indicated that %C differed across groups and across S/Ns. In contrast, P(A) and B differed as a function of S/N but did not differ between hearing-impaired and normal-hearing groups. PMID- 4043578 TI - Relative mortality of type 1 (insulin-dependent) diabetes in Denmark: 1933-1981. AB - The relative mortality of Type 1 (insulin-dependent) diabetes in Denmark during the period 1933-1981 was studied using a modification of Cox's regression model on the basis of two patient populations, ascertained in different ways and independently of each other. Initial analysis showed that the two groups could be combined completely into one common analysis. Relative mortality was the same for both sexes. The additional variables studied were age at diagnosis, current age, calendar year at diagnosis and calendar time during follow-up. All these interrelated variables were accounted for in the analysis. The analysis showed that relative mortality decreased with increasing age at diagnosis; increased from 1933 to a maximum in about 1965, after which it decreased; increased with increased duration of diabetes to a maximum at 15-25 years, after which it declined. PMID- 4043577 TI - Real and artefactual erythrocyte swelling in hyperglycaemia. AB - The mean erythrocyte volume of patients with acute diabetic decompensation was determined by Coulter measurement and found to be elevated above normal (mean increase 5.5 mu3). Experiments in vitro revealed this to be an artefact associated with Coulter determination. A more reliable estimate of in vivo erythrocyte volume can be obtained from centrifugated haematocrit and erythrocyte count. With this method, true erythrocyte swelling parallel to glucose concentration was observed when erythrocytes were exposed to isotonic glucose NaCl solutions. This volume increase resulted from decreased sodium concentration and was in the order of 0.5-1.0 mu3 per mmol/l of sodium. Glucose was osmotically ineffective. Similar volume changes were documented in a diabetic patient parallel to his daily variations of blood glucose. In severe diabetic decompensation, dehydration usually prevents an increase in erythrocyte volume. We conclude that hyperglycaemia is associated with erythrocyte swelling if total serum tonicity remains within the normal range. PMID- 4043579 TI - Glycosylated haemoglobins in normal pregnancy. PMID- 4043580 TI - Intact glucose oxidation in human fetal pancreas. PMID- 4043581 TI - Exercise as a provocative test in early renal disease in type 1 (insulin dependent) diabetes: albuminuric, systemic and renal haemodynamic responses. AB - The value of exercise as a provocative test for early renal disease in Type 1 (insulin-dependent) diabetes was re-evaluated. Three carefully characterized groups of males were studied: 10 non-diabetic controls, 16 diabetic patients (group 1) with normal urinary albumin excretion (less than 15 micrograms/min) and 14 Albustix-negative diabetics (group 2) with increased urinary albumin excretion (15-122 micrograms/min). Assignment to a study group was made on the basis of three 24-h urine collections, and the groups were well matched for age, weight, height, and serum creatinine concentration. The two diabetic groups were similar with regard to duration of disease (13 +/- 6 versus 16 +/- 3 years), metabolic control (HbA1c: 8.4 +/- 1.4 versus 8.7 +/- 1.3%) and degree of diabetic complications (beat-to-beat variation and retinopathy). An exercise protocol of 450 and 600 kpm/min workloads was employed. In the resting state group 2 patients had elevated systolic blood pressure compared with the normal subjects (132 +/- 13 versus 119 +/- 9 mmHg), and their glomerular filtration rate was significantly reduced compared with group 1 (123 +/- 19 versus 138 +/- 15 ml/min per 1.73 m2, p less than 0.05). During exercise the urinary albumin excretion rate increased significantly in all three groups (normal subjects: 6 +/- 0.7 to 8 +/- 1.3 (microgram/min); group 1: 6 +/- 0.6 to 9 +/- 1 microgram/min and group 2: 48 +/- 10 to 113 +/- 23 micrograms/min), the relative increase being higher in group 2 (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4043582 TI - An analysis of epidemiological data in HLA-typed diabetic children. AB - To clarify the heterogeneity of Type 1 (insulin-dependent) diabetes mellitus, differences between patients with different HLA risk antigens were investigated with regard to sex, age at diagnosis, season of year and calendar year at diagnosis of the disease. The study consisted of 293 HLA-typed patients from the Department of Paediatrics, University of Oulu, Oulu, Finland. HLA-Dw2 was extremely rare among diabetic patients, whereas Dw3 and Dw4 were associated with increased risk in this as in other series. Male patients more often had the HLA A1 antigen than females. On comparison of the Dw3 positive patients, boys more frequently had the combination A1,B8 than girls. A1,B8-positive patients were more often diagnosed during the warm months, in the late summer and autumn. Patients with both Dw3 and Dw4 were younger at diagnosis when compared with the rest of the patients. The results support the concept of heterogeneity in the pathogenesis of Type 1 diabetes associated with HLA-linked genetic determinants. PMID- 4043583 TI - Incidence of diabetes in Scottish children. PMID- 4043584 TI - Characterization of alkaline phosphatase from primordial germ cells and ontogenesis of this enzyme in the mouse. AB - The physical characteristics of nonspecific alkaline phosphatase (ALP) from both mouse primordial germ cells (PGCs) and gonads were compared with corresponding samples from other organs at different developmental stages. Combining a cytochemical approach with polyacrylamide gel electrophoresis and the use of specific inhibitors, as well as neuraminidase treatment, heat sensitivity tests, and molecular-mass criteria, it was found that only one ALP isoenzyme was present in all organs up to day 14 of gestation. Distinct ALP isoenzymes first appeared in the small intestine on day 15 and, thereafter, in all other tissues except the gonads. In these organs, the embryonal ALP isoenzyme seemed to be retained until adulthood. Although the placenta had a different ALP isoenzyme than the embryo at all stages, this isoenzyme was found to be similar to that in the maternal decidual tissues. Therefore, we conclude that the mouse embryo only expresses one type of ALP that can be considered "embryonal", regardless of the organ in which it first appears, and that this ALP is conserved in the gonads. PMID- 4043585 TI - Psoriatic hair-follicle cells. II. Morphological differentiation of outer root sheath cells in culture. AB - Psoriatic human hair-follicle keratinocytes were cultured and then examined using light and electron microscopy. In comparison to control cultures derived from non psoriatics, there were significant differences: stratification in general was more extensive; suprabasal cells were flat instead of round; there were almost no depositions of basal lamina or of cellular debris on the growth substrate; numerous membrane coating granules and a few keratohyalin granules were present earlier in psoriatic cultures than in control cultures; and the differentiation pattern resulted in an earlier appearance of corneocyte-like cells, and clusters of these corneocyte-like cells appeared to have been shed into the culture medium. As in control cultures, no distinct stratum corneum was found. Whether these differences between psoriatic cultures and control cultures reveal an aberrant differentiation pattern for psoriatic cells in vitro is as yet unknown: due to the faster outgrowth in psoriatic cultures, a multilayered and therefore further-differentiated structure near the hair follicle could be obtained more rapidly in psoriatic than in normal skin. PMID- 4043586 TI - On predicting environmentally-induced human reproductive hazards: an overview and historical perspective. PMID- 4043587 TI - Recognition, evaluation, and control of chemical embryotoxins in the workplace. PMID- 4043588 TI - New mechanistic models for risk assessment. PMID- 4043589 TI - Absence of mutagenic activity for monosodium cyanurate. AB - The mutagenic potential of monosodium cyanurate was evaluated using in vitro and in vivo tests. All in vitro tests were carried out in the presence and absence of metabolic activation. In each assay, the highest concentration tested generally exceeded the solubility of monosodium cyanurate in the incubation medium. In the Salmonella microbial assay, monosodium cyanurate was not mutagenic towards test strains TA 98, 100, 1535, and 1537 up to a concentration of 10,000 micrograms/plate. Monosodium cyanurate did not induce forward mutations at the TK locus of L5178Y mouse lymphoma cells up to a concentration of 2000 micrograms/ml. No significant increases in sister chromatid exchanges were observed when monosodium cyanurate was incubated with Chinese hamster ovary cells at concentrations up to 1500 micrograms/ml. In an in vivo test, rats were administered monosodium cyanurate by gavage at single dosages up to 5000 mg/kg and killed 24 and 48 hr after dosing. Bone marrow cells were collected and examined for chromosomal aberrations. At the time points examined, there was no evidence of monosodium cyanurate-induced chromosomal aberrations in rat bone marrow cells. PMID- 4043590 TI - Studies on reproduction in rats with meclofenamate sodium, a nonsteroidal anti inflammatory agent. AB - Reproduction and teratology studies were performed in rats given meclofenamate sodium, a nonsteroidal anti-inflammatory agent. Dosages of 0, 3, 6, and 9 mg/kg were administered orally as dietary admixtures in the Fertility and Perinatal Postnatal studies. In the Teratology study, dosages of 10, 12, 15, and 20 mg/kg were administered by intragastric intubation. In the Male-Fertility study no adverse effects on fertility or litter and offspring parameters were observed in two generations. In the Female-Fertility and Perinatal-Postnatal studies, maternal toxicity (death associated with intestinal ulceration and adhesions) was particularly evident during lactation. Prolonged gestation periods, decreased weanling weights, and increased weanling mortality were evident at dosages of 6 and 9 mg/kg. Increased postimplantation loss occurred at 6 and 9 mg/kg in the Term Sacrifice subgroup of the Female-Fertility study. Fertility rates were unaffected and all other litter and offspring parameters of the F1 and F2 generations appeared normal. In the Teratology study no adverse effects on embryonic or fetal development were evident at maternally toxic dosages up to 20 mg/kg. PMID- 4043591 TI - Effects of ClO2 on the absorption and distribution of dietary iodide in the rat. AB - Aqueous chlorine dioxide (ClO2), an alternative disinfectant for drinking water, was found to decrease gastrointestinal (GI) bioavailability of dietary iodide. It has been previously reported that subchronic exposure to ClO2 decreases thyroxine (T4) levels in nonhuman primates. In this study in vitro experiments with animal feed, isolated rat stomachs, as well as in vivo studies with intact rats, showed that ClO2 in drinking water (at in situ concentrations as low as 2 ppm) oxidizes iodide to its reactive elemental (radical) state, binding it to organic substances present in the GI tract. A single instance of acute exposure to ClO2, however, did not decrease blood iodide levels, or thyroid glandular uptake of iodine. PMID- 4043592 TI - Hypophagia-induced weight loss in mice, rats, and guinea pigs treated with 2,3,7,8-tetrachlorodibenzo-p-dioxin. AB - C57BL/6 mice treated with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD; 360 micrograms/kg) displayed a significant reduction in feed intake and body weight until just before death, when they developed ascites and subcutaneous edema. This caused body weight of the mice that died to suddenly increase during the terminal stage of toxicity. TCDD-treated mice that survived did not develop ascites or edema, and maintained a body weight that was slightly less than that of pair-fed mice. Cumulative lethality in TCDD-treated mice (69%) was greater than that of pair-fed controls (14%). In guinea pigs treated with TCDD (2 micrograms/kg) both the time course and magnitude of hypophagia were closely associated with weight loss. Pair-fed guinea pigs did not lose quite as much weight as TCDD-treated animals because their total body water content was higher. Water intake in pair fed guinea pigs was greater than that of TCDD-treated animals. The time course and magnitude of lethality tended to be similar in TCDD-treated guinea pigs (81%) and pair-fed controls (64%). In Fischer F-344 rats treated with TCDD (100 micrograms/kg) body weight loss was associated with a reduction in both feed and water intake. The time course and magnitude of weight loss in TCDD-treated and pair-fed rats was essentially identical. Lethality was higher in TCDD-treated rats (95%) than pair-fed control animals (48%). Taken together, these findings suggest that hypophagia is responsible for the loss of adipose and lean tissue in mice, guinea pigs, and rats treated with a LD70-95 dose of TCDD. Under these dosage conditions, weight loss contributes more to the lethality of guinea pigs than to that of Fischer F-344 rats or C57BL/6 mice. PMID- 4043593 TI - Aryl hydrocarbon hydroxylase induction in adult rat hepatocytes in primary culture by several chlorinated aromatic hydrocarbons including 2,3,7,8 tetrachlorodibenzo-p-dioxin. AB - The induction of aryl hydrocarbon hydroxylase (AHH) by Aroclor 1254, 2,3,7,8 tetrachlorodibenzo-p-dioxin (TCDD) and other polychlorinated organic compounds was examined in primary cultures of adult rat hepatocytes isolated by a collagenase perfusion technique. Following exposure of fresh hepatocyte cultures to 1 microgram/ml Aroclor 1254, AHH induction was undetected for 48 hr and then increased dramatically up to 96 hr. Cultures maintained in control medium for either 24, 48, or 72 hr prior to a 24-hr exposure to Aroclor 1254 displayed significant inducible AHH which was sustained to 96 hr. AHH induction was extremely sensitive to two planar polyaromatic hydrocarbons, 2,3,7,8-TCDD and 2,3,7,8-tetrachlorodibenzofuran, and the PCB congener 3,4,3',4' tetrachlorobiphenyl, but insensitive to 2,6-dichlorodibenzofuran, 2,5,2',5' tetrachlorobiphenyl, 2,4,5,2',4',5'-hexachlorobiphenyl, and hexachlorobenzene. The induction of AHH activity in primary cultures of adult rat hepatocytes may represent a useful bioassay for screening extracts of foodstuffs, biological fluids, or environmental samples for dioxin-like activity. PMID- 4043594 TI - Metabolism and disposition of dipropylene glycol monomethyl ether (DPGME) in male rats. AB - Male Fischer 344 rats were given a single oral dose of approximately 1289 mg/kg (8.7 mmol/kg) of [14C]DPGME. After dosing, expired air, excreta, and tissues were analyzed for 14C activity, and metabolites in urine were isolated and identified. Approximately 60% of the administered 14C activity was excreted in urine, while 27% was eliminated as 14CO2 within 48 hr after dosing. DPGME, PGME, dipropylene glycol, propylene glycol, as well as sulfate and glucuronide conjugates of DPGME were identified in urine of animals given [14C]DPGME. Results of the study indicate that DPGME is metabolized via the same routes to the same general types of metabolites as previously identified for propylene glycol monomethyl ether (PGME). PMID- 4043595 TI - Teratological assessment of methanol and ethanol at high inhalation levels in rats. AB - Alcohols are widely used as industrial solvents. In spite of the fact that ethanol is a human teratogen, there has not been systematic investigation of the potential teratogenic effects of other alcohols, particularly using the inhalation route of exposure, as would be appropriate in assessing occupational and environmental types of experience. As part of a large teratological examination of industrial alcohols, methanol and ethanol were administered by inhalation to groups of approximately 15 pregnant Sprague-Dawley rats. Methanol was administered at 20,000 ppm (20ME), 10,000 ppm (10ME), 5000 ppm (5ME), and 0 ppm (MECO) for 7 hr/day on Days 1-19 of gestation (Days 7-15 for 20ME). Ethanol was administered at 20,000 ppm (20ET), 16,000 ppm (16ET), 10,000 ppm (10ET), and 0 ppm (ETCO) for 7 hr/day on Days 1-19 of gestation. Dams were sacrificed on Day 20 (sperm = Day 0). One-half of the fetuses were examined using the Wilson technique for visceral defects, and the other half were examined for skeletal defects. The highest concentration of methanol (20ME) produced slight maternal toxicity and a high incidence of congenital malformations (p less than 0.001), predominantly extra or rudimentary cervical ribs and urinary or cardiovascular defects. Similar malformations were seen in the 10ME group, but the incidence was not significantly different from controls. No adverse effects were noted in the 5ME group. Dams in the 20ET group were narcotized by the end of exposure, and maternal weight gain and feed intake were decreased during the first week of exposure. The 16ET dams had slightly depressed weight gain (p less than 0.01) during the first week of exposure, but there were no significant effects on feed consumption. There was no definite increase in malformations at any level of ethanol, although the incidence in the 20ET group was of borderline significance. PMID- 4043596 TI - Subchronic toxicity studies of N-D-ornithyl amphotericin B methyl ester in dogs and rats. AB - Two subchronic studies were conducted to assess the potential toxicity of N-D ornithyl amphotericin B methyl ester (OAME). In both studies the comparative control substance was amphotericin B (AMB). Dogs (5/sex/group) were given OAME (82% pure, based on high-pressure liquid chromatographic (HPLC) analysis) at 0.6, 2.5, and 10 mg/kg or AMB at 0.6 mg/kg intravenously once daily for 3 months. Two dogs per sex per group were retained for a 7-week postdose observation period. Rats (15/sex/group) were given daily doses of OAME at 4, 12, 24, and 36 mg/kg or AMB at 5 and 12 mg/kg intraperitoneally for 3 months. The principal organs of toxicity in both species were the liver, kidneys, and circulating erythrocytes. Hepatic changes in dogs consisted of periportal and centrilobular inflammation in animals of all dosed groups and were equivalent in dogs given 0.6 mg/kg OAME or AMB. In rats, acute hepatic necrosis with periportal, centrilobular, or panlobular distribution in animals of all OAME (except 4 mg/kg) and AMB-dosed groups was observed. These changes were equivalent in the 36-mg/kg OAME- and 12 mg/kg AMB-dosed animals. Renal changes, evidenced by increases in serum urea nitrogen water consumption, urine volume, decreased urine osmolality, and renal tubular changes (ranging from degeneration and regeneration to necrosis), were observed in both species. In dogs, these changes in the OAME-dosed animals were less severe at all doses than those observed in the AMB-dosed dogs. Renal changes in rats, which were mild in comparison to the dogs, were equivalent at doses of 5 and 12 mg/kg AMB and 36 mg/kg OAME. Decreased erythrocyte counts, hematocrit, and hemoglobin values were observed in both species. Unique to the dog study, however, were irreversible behavioral (somnolence, ataxia, tremors, and compulsive searching) and/or morphologic brain changes (gliosis with astrocytic hypertrophy and hyperplasia) at doses of 2.5 and 10 mg/kg OAME. Similar changes were observed in two dogs given 10 mg/kg OAME (100% pure, based on HPLC analysis) in a 6-week pilot study, indicating that the neurological changes were induced by OAME rather than by an impurity. These changes appear related to prolonged exposure to high plasma concentrations of OAME. PMID- 4043597 TI - In vitro bioassay for dioxinlike activity based on alterations in epithelial cell proliferation and morphology. AB - 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) has been shown to induce changes in morphology and proliferation characteristics of a nonkeratinizing derivative (XBF) of a keratinizing epithelial cell line (XB), cloned from a mouse teratoma, when cocultured with irradiated feeder cells. Polychlorinated dibenzodioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), polychlorinated biphenyls (PCBs), polynuclear aromatic hydrocarbons (PAHs), and pesticides (24 compounds in total) were tested for their ability to induce these effects. The results indicated that, for the representative compounds tested, these changes are relatively specific for-and that the XBF cells are extremely sensitive to--PCDDs and PCDFs. TCDD was the most potent congener tested, capable of inducing the effects at a concentration as low as 10(-11) M. The activities of other tested PCDDs and PCDFs ranged from 10(-1) to 10(-3) of TCDD activity. The PCBs, PAHs, and pesticides had lower activities ranging from 10(-3) to 10(-6) that of TCDD. This assay system using XBF cells cocultured with irradiated 3T3 fibroblast feeder cells was examined as a possible in vitro screening assay for dioxinlike activity by testing benzene extracts of soot from a fire involving a PCB-containing transformer. The results were compared to a high-resolution gas chromatographic/mass spectrometric analysis for total PCDFs in the same samples. This comparison showed a good correlation, suggesting that the XBF-3T3 system has potential for use as a semiquantitative assay for dioxinlike activity. PMID- 4043599 TI - Toxic effects on the visual system of diaminodiphenoxybutane, quinine, and ethambutol in conscious dogs. AB - The effects of diaminodiphenoxybutane (DAPB), quinine, and ethambutol (EB) on the electroretinogram (ERG) and the visual evoked potential (VEP) were examined in conscious dogs. In dogs receiving repeated oral doses of 100 mg/kg/day for 4 days or a single iv dose of 30 mg/kg of DAPB, the amplitudes of the ERG a- and b-waves were markedly depressed and the peak latency of the VEP first wave was prolonged. Thereafter, ophthalmoscopic changes consisted of mottled discoloration of the fundus, loss of visual placing reaction, and dilatation of the pupils with reduction of the pupillary light reflex were observed. These abnormal signs disappeared even though the marked depression in amplitudes of the ERG a- and b waves and the prolongation in latency of the VEP first wave continued. A single iv dose of quinine at 50 mg/kg caused a slight depression of the amplitude of the ERG, whereas the VEP remained relatively unaffected. In a dog receiving a single iv dose of quinine at 100 mg/kg, both the ERG and VEP were depressed, and a slight dilatation of the pupils with reduction of the pupillary light reflex and an impairment of visual placing reaction were observed transiently. There was no abnormality in the ocular fundus in either animal receiving quinine. The dogs receiving repeated sc doses of EB at 100, 200, and 400 mg/kg/day for 4 weeks each, for a total of 12 weeks, showed extensive decoloration of the tapetal fundus. However, neither the ERG nor VEP showed any significant abnormalities, and no behavioral signs of visual disturbance were observed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4043598 TI - Carcinogenicity of chloroform in drinking water to male Osborne-Mendel rats and female B6C3F1 mice. AB - The carcinogenic activity of chloroform administered at 0, 200, 400, 900, and 1800 mg/liter in drinking water was studied in male Osborne-Mendel rats and female B6C3F1 mice. A second control group was included in the study and was restricted to the water consumption of the high-dose group. Animals were maintained on study for 104 weeks. Group sizes were adjusted at low doses such that a detectable tumor response would result at the lowest dose if there was a linear relationship with dose, and the higher doses produced responses similar to previous carcinogenesis bioassays of chloroform. The primary finding was that chloroform increased the yield of renal tubular adenomas and adenocarcinomas in male rats in a dose-related manner. For the high-dose group, which corresponded to a time-weighted average dose of 160 mg/kg per day for 104 weeks, there was a 14% incidence of renal tubular adenomas and adenocarcinomas, vs 1% in the control group. This compares to a 24% incidence observed when 180 mg/kg per day of chloroform was administered for 78 weeks in earlier studies. In contrast, chloroform in the drinking water of mice failed to increase the incidence of hepatocellular carcinomas in female B6C3F1 mice. The highest dose group received a time-weighted average dose of 263 mg/kg for 104 weeks, resulting in a 5% combined incidence of hepatocellular adenoma and carcinoma relative to a 6% incidence in the control groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4043600 TI - A 90-day vapor inhalation toxicity study of decalin. AB - A subchronic 90-day inhalation study was conducted to determine the toxic effects of decalin, a commonly used industrial solvent. Experimental groups consisting of male and female beagle dogs, male and female Fischer-344 rats, and female C57BL/6 mice were continuously exposed to decalin concentrations of 5 or 50 ppm. An unexposed control group was also maintained. All dogs and a portion of each rodent group were sacrificed and examined at exposure termination, while the remaining rodents were held for observation up to 21 months postexposure. No distinct exposure-related lesions were noted in dogs. Dog body weights, organ weights, and blood clinical pathology were also normal. At exposure termination hepatocellular cytoplasmic vacuolization was noted in female mice exposed to both concentrations. This liver tissue change was reversible and was not a significant finding in female mice examined during the 21-month postexposure observation period. In male rats, decalin exposure produced nephropathy characterized by hyaline droplets, necrosis, and intratubular casts. Accentuated tubular degeneration and medullary mineralization were noted in exposed rats held for long-term postexposure observation. There was no associated abnormal increase in mortality nor alterations in serum, blood urea nitrogen, or creatinine levels. Female rats were free of decalin-induced renal damage. There was a slightly greater incidence of commonly occurring pituitary tumors in both mice and rats; however, the tumor incidence was not dose related. The results of this study suggest that the toxic effects of decalin are similar to those previously described for other hydrocarbon solvents and fuels. PMID- 4043601 TI - Quantity versus quality: is stress the link? PMID- 4043602 TI - Work satisfaction of general practitioners and the quality of patient care. AB - The emotional reactions of 57 general practitioners to three aspects of work was assessed by means of questionnaires. The quality of patient care was assessed by means of observations of general practice consultations, assessment of audiotaped consulting hour contacts and an analysis of the referral and prescription figures. A distinction was made between the degree of positive and the degree of negative feelings general practitioners have about their work. Many positive feelings (satisfaction, feeling at ease) correlated with more openness to patients, more attention to psychosocial aspects of the complaints but also with a higher rate of referral to medical specialists. On the other hand, many negative feelings (frustration, tension, lack of time) correlated with a high prescription rate and with giving little explanation to patients. To some extent the way that work is experienced by general practitioners correlated with the quality of care for the patients, but what constitutes cause and effect requires further study. A reflection of a doctor's own feelings about work should become part of training, continuing education and medical audit programmes. PMID- 4043603 TI - Measurement of stress as it affects the work of the general practitioner. AB - This paper describes a preliminary study which collected information on the work of 18 general practitioners during a total of 52 days, and also recorded their feelings of pressure and stress from hour to hour throughout each day. The instruments used to record information on day-to-day activities and to measure self-perceived pressure, stress and arousal are described. The reliability and validity of the methods used are discussed, and some suggestions made for future development. A few preliminary findings are presented. PMID- 4043604 TI - Does labelling and treatment for hypertension increase illness behaviour? AB - This study looked at the possible harmful effects of detection and treatment for hypertension. Patients with borderline blood pressure (diastolic 96-109 mmHg) were randomized into two groups: an intervention group receiving treatment for hypertension and a control group not told about any problem and left untreated. The morbidity in these two groups were studied for differences. During the period studied, the patients in the investigation group saw the doctor more frequently and had a larger number of diseases classified than the control group. When consultations involving hypertension and its follow up were excluded, however, no differences were demonstrable between the groups. Problem behaviour, psychosomatic and functional affections and symptom diagnoses were evenly distributed over the two groups. The difference in blood pressure between the two groups after completion of the study was not marked: the decrease in diastolic blood pressure averaged 7.6 mmHg in the control group versus 9.1 mmHg in the intervention group. In cases where the initial blood pressure values are only slightly raised, careful monitoring of blood pressure over a long period seems to be as effective as treatment for hypertension. The general practitioner should focus especially on anticipation in this sense. PMID- 4043605 TI - Physician redistribution: a worldwide medical problem. AB - The Rural Physician Associate Program may be the only undergraduate medical education programme in the world that has been able to successfully redistribute family physicians into geographically isolated areas where there are serious shortages of doctors. A number of factors are essential to this success of the scheme: absolute moral and economic support from the people and their elected leaders; a willingness of medical school faculty to give academic and clinical support to an ongoing, long-term effort with undergraduate medical students and practising family physicians; the free volunteering by rural practising physicians to make the commitment to teach the medical students for over nine months and to pay these students up to +5000; the emphasis of the programme to be placed on the importance of using a biopsychosocial-sexual model in creative problem solving; audiovisual taping, behavioural medicine seminars and family therapy sessions are additional curriculum tools in helping students and physicians care for people with somatic complaints; the student's spouse and children to be included in the professional conditioning experience; there is no legal commitment for the student and family to return to rural Minnesota after the programme. PMID- 4043606 TI - A graduate programme for academic family physicians. AB - The paper describes a graduate studies programme designed to prepare outstanding family physicians for academic leadership and reports an evaluation of the programme. The programme aims to produce academic family physicians who exhibit certain qualities: outstanding clinical skills, professional interest in the organization and transmission of knowledge, and a scholarly approach through research and skills of leadership. The course includes clinical and teaching practice, formal course work and a scholarly thesis; the emphasis is on teaching and learning, theoretical foundations of family medicine, whole person medicine, research design and techniques, ethical decision making, and administration of organizations. A survey of the first 30 graduates of the programme indicated that the majority did more clinical teaching, small group teaching, research, writing and administration than before the course. The graduates' opinions of the programme indicated the extent to which the programme goals have been met; to provide a coherent learning experience integrating the art, science and technology of the discipline of family medicine. PMID- 4043607 TI - Milestones or furlongstones? AB - A study was carried out over five years of 15000 children aged between one day and three months. It was observed that many infants passed their important 'milestones' much earlier than is suggested in present textbooks. A plea is made for discarding the traditional ages for the various landmarks in the development of a child. The changes of mental development are very important in the first three months and during the three to six months period the baby seems to be merely consolidating more methodically what he was doing less conveniently during the first three months. PMID- 4043609 TI - Health outcomes in primary care: an approach to the problems. PMID- 4043608 TI - Perinatal mortality in infants of two different ethnic groups. AB - In a retrospective survey of 1433 Chinese and 1130 Gurkha (Nepali) births in an Armed Services environment in Hong Kong, neonatal mortality rates were analysed according to birthweight. The data thus obtained were compared with similar data from published surveys with the aim of ascertaining any differences in mortality rates. PMID- 4043611 TI - Grouping together clinically homogeneous terms. PMID- 4043610 TI - Measuring the outcome of general practitioner care. PMID- 4043612 TI - Primary health care in Portugal: reflections on a Portuguese-Norwegian development project. PMID- 4043613 TI - [Most important trends in the development of human physiology during the 40 years since the victory of the Soviet people in World War II]. PMID- 4043614 TI - [Thermographic indices of the responses of the brain to visual stimuli]. PMID- 4043616 TI - [Interrelations between different ranges of bioelectrical activity of the brain]. PMID- 4043615 TI - [Neurophysiologic possibilities for studying evoked changes in the frequency of neuron discharges by the technic of component analysis]. PMID- 4043617 TI - [Reactions of neurons and evoked potentials in subcortical structures of the brain during visual discrimination. I. Defining the problem and principal methods of solving it]. PMID- 4043618 TI - [Effect of spatial-frequency filtration and length of a letter of distinguishable images on the psychophysiologic characteristics of their discrimination]. PMID- 4043620 TI - [Hemispheric asymmetry in the electroencephalogram of twins]. PMID- 4043619 TI - [Prestimulus EEG and evoked potentials in man during discrimination of a meaningful photic stimulus]. PMID- 4043621 TI - [Features of the emotional reactions of persons with different levels of neuroticism]. PMID- 4043622 TI - [Status of motor neurons and the monosynaptic reflex arc before a simple voluntary movement]. PMID- 4043623 TI - [Determination of the axes of force of the plantar flexors of the foot by a biomechanical method]. PMID- 4043624 TI - [Effect of collateral circulation on left ventricular function at rest and during exertion in patients who have sustained infarctions of the posterior wall of the myocardium]. PMID- 4043625 TI - [Impedance of the arterial system and cardiac activity]. PMID- 4043626 TI - [Features of the respiration of residents of the North-East USSR]. PMID- 4043627 TI - [Indices of external respiration among young athletes during adaptation to high environmental temperature]. PMID- 4043628 TI - [Indices of humoral-hormonal regulation of functions in highly skilled chess players]. PMID- 4043629 TI - [Effect of 24-hour sleep deprivation on the metabolism of biogenic amines]. PMID- 4043630 TI - [Characteristics of electrocutaneous conductivity in healthy men and women]. PMID- 4043631 TI - [Electromyographic criteria for the evaluation of operators]. PMID- 4043632 TI - [Changes in indices of the cardiorespiratory system in the presence of a local static load]. PMID- 4043634 TI - [Adaptation of the human body to repeated brief exposure to a hot environment]. PMID- 4043633 TI - [Relation between the spectral composition of the electroencephalogram and parameters of intermittent photostimulation]. PMID- 4043635 TI - [Changes in the sensitivity of the body to triiodothyronine and adrenaline as a result of smoking]. PMID- 4043637 TI - [Intensification of the somnogenic effect of heat pulsation by simultaneous exposure of 2 reflexogenic zones]. PMID- 4043636 TI - [Visual perception of the shape of a surface from half-tone images]. PMID- 4043638 TI - [Useful and useless controversies regarding contraction bands and the pathogenesis of ischemic cardiomyopathy]. PMID- 4043639 TI - [Identification of patients with stenosis of the main trunk of the left coronary artery by ergometric variables]. AB - In 354 patients with coronary artery disease (9 with greater than or equal to 90%, 42 with 50-75% and 303 with no left main (LM) stenosis, prevalence of ergometric criteria of severe disease was considered. In patients with LM stenosis were more frequent: work load less than or equal to 75 watt (p less than 0,001); ST depression greater than 2 mm (p less than 0,01); 3 or more leads involved (p less than 0,05); no increment of heart rate (p less than 0,01) or of blood pressure (p less than 0.01). Work load had the best predictive value (30%) of LM stenosis, associated with a reasonable sensitivity (55%). Combination ST depression + heart rate or work load + blood pressure had a predictive value of 100%, but minimal sensitivity (8%). In detecting greater than or equal to 90% LM stenosis heart rate had the best predictive value (13%), associated with high sensitivity (78%). Presence of 2 any criteria could detect all greater than or equal to 90% LM stenosis (sensitivity 100%, predictive value 11%). ST depression + heart rate had a predictive value of 100% and a sensitivity of 44%. It is concluded that no single or associated exercise variable has both high sensitivity and high predictive value of LM stenosis. PMID- 4043640 TI - [Role of bidimensional echocardiography in the study of aneurysms of a membranous septum associated with defects of the intraventricular septum of perimembranous type]. AB - Spontaneous closure of ventricular septal defects (V.S.D.) is frequently associated with aneurysm of the membranous septum (A.M.S.). However, the presence of A.M.S. may not be always indicative of closure or diminution of the size of V.S.D.. The purpose of this paper is to present the role of two-dimensional echocardiography (2D E) in the identification and assessment of A.M.S.. The dimensions, morphology and motion of A.M.S. during the cardiac cycle was also analyzed frame by frame by the 2D E technique. 20 cases of A.M.S. associated with perimembranous V.S.D. are included in this study. The most useful echocardiographic section in the assessment of A.M.S. was the apical four-chamber view with slight cranial angulation (sensitivity = 100%). The frame-by-frame analysis of A.M.S. motion during the cardiac cycle may give useful informations concerning the hemodynamic and physiopathologic abnormalities associated with the underlying congenital heart diseases. We conclude the 2D E seems to be useful in the identification and assessment of A.M.S. associated with perimembranous V.S.D. PMID- 4043641 TI - [Aortic coarctation and associated abnormalities in the first year of life. Echocardiographic diagnosis]. AB - Thirty-eight cases of "Aortic Coarctation Syndrome" presenting in the first year of life (66% under 3 months of age) were studied with cross-sectional echocardiography. Direct imaging of the coarctation was achieved in 75% of cases. Patent ductus arteriosus was present in 60% (80% before three months). Associated anomalies were present in 63%; VSD 29%, Aortic stenosis 16%, Mitral stenosis 16%, AV Canal 5%, Taussig Bing type of DORV 5%, Corrected transposition with VSD 3%, Ebstein anomaly 3%, Univentricular A-V connection 3%. The results were compared with angiographic and/or surgical and/or autoptic findings. The echocardiographic diagnosis proved to be very reliable in most cases. The policy of sending to surgery most neonates and infants with coarctation of the aorta without preoperative catheterization is discussed. PMID- 4043642 TI - [Cardiopathy and acute cerebrovascular insufficiency. Prospective study with two dimensional echocardiography]. AB - Many cardiac disorders can cause acute cerebrovascular insufficiency. The spectrum of potentially embolic cardiac conditions is wide; early recognition may determine a definite change in the management and prognosis of patients. In recent years the relevance of echocardiography in the screening of patients with cerebral ischemia has been emphasized. In order to identify potentially embolic cardiac conditions, 180 consecutive non selected patients with cerebrovascular insufficiency, underwent a clinical cardiological evaluation and an echocardiogram. The study population included 132 men and 48 women; the mean age was 51.7 years (range 19 to 72 years). A technically adequate echocardiogram was obtained in 153 patients. In 131 patients echocardiography was negative; cardiac lesions were detected in 22 patients (14.4%): mitral stenosis in 2, calcified aortic stenosis in 1, valvular endocarditis vegetations in 3, dilatative cardiomyopathy in 2, hypertrophic cardiomyopathy in 4, mitral valve prolapse in 4, regional left ventricular diskynesia in 5, mitral anulus calcification in 1. Patients were divided into 3 groups according to the results of cerebral angiography: 68 patients with normal angiography (Group I), 54 patients with atheromasic lesions on cerebral angiography (Group II), 31 patients in whom cerebral angiography was not performed (Group III). A higher incidence of cardiac diseases was found in the patients of Group I. The lack of lesions on cerebral angiography and the presence of embolic high-risk cardiac conditions strengthened a causal relationship of the cardiac disorder with cerebrovascular insufficiency in 10 of the 23 patients. In the mean follow-up period of 18 months of these 10 patients who underwent cardiac surgery or anticoagulation, no further attacks of cerebrovascular insufficiency were observed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4043643 TI - [Angioplasty of the common trunk of the left coronary artery with venous patch]. AB - Surgical angioplasty of the left main coronary artery for severe iatrogenic stenosis has been done on a 40 year old female patient operated upon five months before for mitral and aortic valve prosthetic replacement. Postoperative angiocardiographic study showed patent left main trunk and the patient is angina free six months post-operatively. Operative indication and surgical technique are discussed as an alternative to aorto-coronary by-pass surgery for left main proximal stenosis without peripheral lesions. It does not result from literature that this surgical technique has ever been employed in patients previously operated with open heart surgery. PMID- 4043644 TI - [A new dual-chamber pacemaker with an automatic antitachycardia system in the treatment of the bradycardia-tachycardia syndrome]. AB - A new dual-chamber pacemaker with automatic tachycardia terminating system was used in three patients with bradycardia-tachycardia syndrome. This pacemaker (Medtronic Symbios 7008) is a multiprogrammable, bipolar device with bidirectional telemetry and six permanent pacing modes (DDD-DVI-VVI-DOO-VOO-AOO). The antitachycardia system can be programmed in two different modes: underdrive dual demand and overdrive atrial burts (1 to 16 stimuli with selectable coupling interval from 135 to 360 msec). The pacing modes are automatically activated when five consecutive R-R cycles shorter than the tachycardia detection interval are sensed. The pacemaker may sense the ventricle (when set on VVI or DVI mode) or sense both the atrium and the ventricle (in DDD mode). The pacemaker was programmed on DVI mode in all three patients, and the overdrive atrial burst program was used for tachycardia termination, with promptly and costantly effective results. The underdrive dual demand program was tested after the implantation, but it did not show constant results because inefficacy or late termination of tachycardias. PMID- 4043645 TI - [Evaluation of left ventricular ejection fraction in coronary disease patients by the gated blood pool method and cineangiography. Critical analysis of divergences between the 2 methods]. AB - In order to assess the reliability of left ventricular ejection fraction as estimated by gated blood pool method, radionuclide angiography (LAO) and single plane (RAO) contrast cineangiocardiography were performed within 14 days in 60 patients with coronary artery disease. The mean value of radionuclide ejection fraction was found to be 55 +/- 16%; contrast cineangiographic ejection fraction was 57 +/- 15%; r = 0.92. In 23 patients with previous anterior myocardial infarction gated blood pool method was found to underestimate left ventricular ejection fraction when compared with contrast cineangiography. The observed underestimation was wide significant in 11 patients with previous anterior infarction, low (less than 50%) radioisotopic ejection fraction and septal akinesia and/or apical dyskinesia; radionuclide ejection fraction = 33 +/- 8%; contrast cineangiographic ejection fraction = 42 +/- 9%; r = 0,76. This study confirms that the values of left ventricular ejection fraction as estimated by gated blood pool method in coronary patients are quite reliable; moreover, the intrinsic variability of the data is low. This may be not true in patients with previous anterior myocardial infarction. The Authors discuss the possible causes of disagreement between radioisotopic and contrastographic ejection fraction in patients with previous anterior infarction and poor left ventricular function: physical problems of measuring ejection fraction by gated blood pool in dilated ventricles; possible mistakes in evaluating blood pool due to the low mobility of the blood mass nearest to the scintillation camera; inhability of contrast cineangiography in RAO to recognize the interventricular septum and evaluate its kinetic abnormalities; unreliability of the geometrical model of revolution elypsoid in calculating end-systolic volumes in ventricles with abnormal wall kinesis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4043646 TI - [Drug blockade of the neurovegetative system in the study of sinus node function]. PMID- 4043647 TI - [Sudden and fatal malfunction of a Bjork-Shiley prosthesis in mitral position due to rupture of the ventricular bracket and disk embolization]. AB - Mechanical complications of prosthetic valves are increasing. The following report describes a case of fracture of a Bjork-Shiley mitral prosthetic strut with dislogment of the valve occluder into the thoracic aorta. At the reoperation a new prosthesis was implanted but the patient died of acute heart failure. The diagnosis of valve disfunction must be made non invasively, because the time required for cardiac catherization usually constitutes a lethal delay. The only hope for survival is prompt surgical treatment. PMID- 4043648 TI - [Supraventricular tachyarrhythmia of a variable degree of atrial synchronization caused by drinking cold water]. AB - We report upon a patient with mitral valve prolapse of mild degree who complained of paroxysmal tachyarrhythmias after drinking ice-cold beverages. It was demonstrated that iced water ingestion was followed, in this patient, by transient episodes of supraventricular tachyarrhythmias. The reproducible induction of acute, transient rhythm disturbance can possibly be explained by the temperature changes of either the pericardium or the left atrial wall, which have been experimentally shown to follow iced water swallowing. Whether this is a direct cause-to-effect phenomenon or one involving a neural mechanism cannot be currently inferred. PMID- 4043649 TI - [Medical role of the levels of medical care]. PMID- 4043650 TI - [Brain levels of dopamine during the estrous cycle in the rat]. PMID- 4043651 TI - [Electrophoretic variants of erythrocyte acid phosphatase in samples from subjects from the Federal District and various states of the Republic of Mexico]. PMID- 4043652 TI - [Lupus nephritis. Unifying criteria: a necessity]. PMID- 4043653 TI - [Intermittent claudication of neurologic origin]. PMID- 4043654 TI - [Multiple cartilaginous exostoses in a family. Relation of its complications and association with coagulopathies]. PMID- 4043655 TI - Effect of truncal vagotomy on neurotensin-like immunoreactivity release in dogs. AB - To elucidate the relationship between the vagus nerve and circulating neurotensin release, mongrel dogs were given an intraduodenal infusion of a 50 ml water solution containing 10 g glucose (n = 4) or 5 g soybean oil (n = 7) over a period of 4 min before and after truncal vagotomy with pyloroplasty. In the prevagotomized animals only a slight increase of neurotensin-like immunoreactivity (NTLI) was observed following glucose infusion, while NTLI in response to fat infusion was significantly increased. After vagotomy, NTLI release following fat infusion was significantly decreased when compared to untreated control animals, suggesting that vagotomy causes a major alteration in circulating NTLI release and that the vagus nerve may play a definite role in fat induced NTLI release. PMID- 4043656 TI - Studies on the effects of estrogen on in vitro antibody production in autoimmune liver diseases, including lupoid hepatitis and primary biliary cirrhosis. AB - Antibody-forming cells produced by adding trinitrophenylated sheep red blood cells (TNP-SRBC) were induced, when peripheral blood mononuclear cells from normal individuals and patients with autoimmune liver diseases, including lupoid hepatitis and primary biliary cirrhosis, were stimulated in vitro with pokeweed mitogen (PWM). Although antibody responses were significantly augmented by adding estrogen simultaneously with PWM to mononuclear cell cultures prepared from normal individuals and autoimmune liver diseases patients, a significant difference was observed according to the concentrations of estrogen between the normal subjects and patients. These observations suggest that a different responsiveness to the different concentrations of estrogen underlines the immunological abnormalities involved in autoimmune liver diseases, including lupoid hepatitis and primary biliary cirrhosis. PMID- 4043657 TI - Sterol and bile acid metabolism after short-term prednisolone treatment in patients with chronic active hepatitis. AB - Serum levels of squalene, cholesterol and bile acid were measured before and after short-term prednisolone administration in patients with chronic active hepatitis. Comparison with normal controls indicated that serum bile acid levels were increased significantly (p less than 0.01) in patients with chronic active hepatitis, but serum levels of squalene and cholesterol did not differ significantly between the two groups. After short-term prednisolone treatment, serum levels of squalene and cholesterol were increased significantly (p less than 0.01) as compared with the pretreatment level. On the other hand, while serum fasting bile acid levels were found to be increased significantly (p less than 0.01), serum clearance after oral administration of ursodeoxycholic acid improved significantly (p less than 0.05) after treatment. These results indicated that short-term prednisolone treatment increases sterol metabolism in the liver in patients with chronic active hepatitis, resulting from an increase in hepatic clearance of bile acids. PMID- 4043658 TI - Proceedings of the international session of the 26th annual meeting of the Japanese Society of Gastroenterology. October 18-20, 1984, Chiba, Japan. Abstracts. PMID- 4043659 TI - Ursodeoxycholic acid treatment of bile reflux gastritis. AB - Intractable epigastric pain associated with nausea and bilious vomiting often follows gastric surgery and has been attributed to reflux of bile and the irritating effects of endogenous bile acids on the gastric remnant. To test the effect of changing bile acid composition of the refluxed material on the symptoms and gastric mucosal histology, 12 patients with symptomatic alkaline reflux gastritis were treated for 1 mo with placebo and for 1 mo with ursodeoxycholic acid, 1000 mg/day. Before treatment, all patients were symptomatic and manifested epigastric pain, nausea, and bilious vomiting. The gastric mucosa was erythematous, friable, and bile stained, and the histology revealed chronic inflammation. No significant change in symptoms was noted during administration of placebo. In contrast, ursodeoxycholic acid treatment resulted in a profound decrease in the intensity and frequency of pain and almost abolished nausea and vomiting. During bile acid therapy the proportion of ursodeoxycholic acid in gastric bile rose to 50% of total bile acids, whereas cholic and deoxycholic acids decreased and chenodeoxycholic acid remained unchanged. The macroscopic and microscopic appearance of the gastric mucosa, however, did not change after 1 mo of ursodeoxycholic acid treatment. These results suggest that increasing the proportion of ursodeoxycholic acid in refluxed gastric bile reduces the pain and frequency of symptoms associated with bile reflux. PMID- 4043660 TI - Natural history of fundic gland polyposis in patients with familial adenomatosis coli/Gardner's syndrome. AB - In order to study the natural history of fundic gland polyposis, 23 patients with familial adenomatosis coli/Gardner's syndrome were examined over a follow-up period ranging from 17 mo to 13 yr (average 6 yr). Examinations included gastric radiography and endoscopy with biopsy. Fundic gland polyps were found in 10 individuals. The size and number of polyps varied considerably. During the follow up period, there was an increase in number or size of polyps, or both, in 5 patients (aged 8-27 yr), a decrease or disappearance in 2 patients (aged 36 and 41 yr), an initial decrease or disappearance followed by a late-occurring increase in 2 patients (aged 28 and 35 yr), In addition, malignant or adenomatous changes of fundic gland polyps were not observed in any patient. Therefore, fundic gland polyposis in patients with familial adenomatosis coli/Gardner's syndrome may appear as early as 8 yr of age. In some patients there is a gradual increase in number and size of polyps, whereas in others, polyp proliferation ceases and polyps may even decrease in number and size. Our findings indicate that the fundic gland polyposis does not require prophylactic surgery and that careful periodic follow-up should suffice. PMID- 4043661 TI - Antibiotic-associated colitis due to Clostridium difficile: double-blind comparison of vancomycin with bacitracin. AB - A randomized double-blind study was carried out in patients with unresolving antibiotic-associated colitis due to Clostridium difficile, to compare the effect of bacitracin (80,000 U/day) with vancomycin (500 mg/day) on the resolution of symptoms, clearance of organism, and prevention of relapse. Forty-two patients with colitis, 9 of whom had a pseudomembrane, were randomized, 21 patients to each treatment group. The two groups were comparable in age, disease severity, and antibiotic exposure. For a 50% reduction in stool frequency the mean times (+/- SE) were 4.1 +/- 0.4 days for bacitracin and 4.2 +/- 0.4 days for vancomycin. Sixteen patients (76%) had symptom resolution after 7 days of treatment with bacitracin, compared with 18 patients (86%) given vancomycin. Patients who failed to respond were crossed over (blind) to the alternative antibiotic, but tended to be refractory to the alternative medication as well. Vancomycin-treated patients had negative toxin (83% vs. 53%, p = 0.04) and negative stool cultures (81% vs. 52%, p = 0.02) more frequently than did those patients given bacitracin. Similar numbers of patients in each group had symptomatic relapse during 1 mo of follow-up, but most of them relapsed yet again after blinded crossover therapy. Although bacitracin was significantly less effective than vancomycin in clearing C. difficile from the stools, both were of similar value in the control of symptoms in a group of patients with predominantly nonpseudomembranous colitis. In view of its low cost, bacitracin is a reasonable first-line alternative to vancomycin in the treatment of antibiotic associated colitis. PMID- 4043662 TI - Evidence for an increased risk of Crohn's disease in oral contraceptive users. AB - The risk of Crohn's disease in relation to oral contraceptive use was evaluated in a hospital-based, case-control study of 57 women with Crohn's disease and 2189 controls with other conditions. The relative risk for oral contraceptive users compared with women who had never used these drugs was 1.9 (95% confidence interval 1.0-3.5). The magnitude of the relative risk estimate was related to the timing and duration of oral contraceptive use. For use within the year before admission to a hospital (recent use), the relative risk estimate was 4.3 (2.1 8.7); the estimate dropped to 1.2 (0.5-2.6) 4 yr after discontinuation of oral contraceptive use. The relative risk estimate for recent use that lasted greater than or equal to 5 yr was 8.0 (3.1-21). The findings are in accordance with earlier reports of an increased risk of Crohn's disease in oral contraceptive users. PMID- 4043663 TI - Effect of magnesium on active and passive sodium transport in the human ileum. AB - The effect of 12.5 mM magnesium chloride on sodium transport in the human ileum in vivo was investigated using segmental perfusion. Choline chloride was used as a control. During perfusion of a balanced electrolyte solution containing isotopes of sodium and chloride, magnesium reduced unidirectional flux of sodium in both directions across the ileum; magnesium had no statistically significant effect on net sodium absorption, on chloride fluxes, or on potential difference. When sodium-free test solutions were infused, magnesium (and calcium) reduced net sodium secretion compared with choline and potassium. These results suggest that magnesium (and calcium) reduce passive sodium movement across ileal mucosa. PMID- 4043664 TI - 16,16-Dimethyl prostaglandin E2 suppresses the increases in the proliferative activity of rat colonic epithelium induced by indomethacin and aspirin. AB - Treatment of rats with indomethacin rapidly increased ornithine decarboxylase (4 h) of colonic mucosa and [3H]thymidine incorporation into colonic mucosal deoxyribonucleic acid (DNA) (1 or 5 days) when this parameter was examined in vivo and ex vivo. The changes in colonic mucosal ornithine decarboxylase and DNA synthesis induced by indomethacin were correlated temporally with suppression of colonic prostaglandin synthesis, as assessed from ex vivo colonic production of prostaglandin E, the dominant prostaglandin product of colon. Autoradiographic studies indicated that the enhancement of proliferative activity of colonic epithelium after treatment with indomethacin for 1 day was confined to the lower third of the colonic crypt (normal proliferative zone). After 5 days of indomethacin treatment, however, there was an extension of the proliferative zone to the upper third of the colonic crypts. Concurrent treatment of rats with the stable prostaglandin E2 analogue, 16,16-dimethyl prostaglandin E2, suppressed indomethacin-induced increases in colonic mucosal ornithine decarboxylase and DNA synthesis. Concurrent administration of 16,16-dimethyl prostaglandin E2 also prevented the extension of the proliferative zone of colonic epithelium induced by 5 days of indomethacin administration. 16,16-Dimethyl prostaglandin E2 alone for 1-5 days had no detectable effects on colonic mucosal ornithine decarboxylase and DNA synthesis compared with corresponding control values. Increases in colonic mucosal DNA synthesis were also induced by treatment of rats for 5 days with aspirin (ASA). The stimulation of colonic mucosal DNA synthesis induced by ASA was significantly suppressed by concurrent administration of 16,16-dimethyl prostaglandin E2 and was also correlated with the inhibition of colonic prostaglandin synthesis by ASA. The colons of rats treated with indomethacin for 1 day or ASA for 5 days appeared normal by light microscopy. However, treatment of rats for 5 days with indomethacin resulted in mild to moderate inflammation of the lamina propria and some goblet cell depletion at the mucosal surface, but no loss of surface epithelium. The ultrastructure of the surface epithelium of the colons of rats treated with indomethacin or ASA was normal as assessed by electron microscopy. The results thus demonstrate that inhibition of local colonic prostaglandin synthesis is associated with increases in the proliferative activity of colonic epithelium, and that these increases are suppressed by administration of 16,16-dimethyl prostaglandin E2.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 4043665 TI - Bone loss in autoimmune chronic active hepatitis on maintenance corticosteroid therapy. AB - To determine the frequency of osteoporosis in patients with autoimmune chronic active hepatitis who are maintained on corticosteroids, both cortical and trabecular bone loss were studied in a group of 36 patients. A significant decrease in both the total trabecular bone volume (p = 0.005) and cortical plate thickness (p = 0.01) of iliac crest biopsy specimens was found in the patients with chronic active hepatitis. Bone mineral content of the radial metaphysis, a site composed of both cortical and trabecular bone, was found to be significantly decreased (p = 0.05). However, no statistical reduction in cortical bone mass of the radial diaphysis and second metacarpal was detected. Altogether, 47% of patients had evidence of either excessive trabecular or cortical bone loss, or both, as judged by histologic and radiologic criteria. The presence of cirrhosis at the time of diagnosis or subsequently did not appear to lead to greater loss of bone mass. However, a weak inverse correlation was found between the product of mean dose and duration of corticosteroid therapy and both the trabecular bone volume and the cortical plate thickness of the iliac crest biopsy specimens. Based on these results, patients with autoimmune chronic active hepatitis on low doses of prednisolone therapy may need to be treated with calcium and vitamin D at an early stage of their disease. PMID- 4043666 TI - "Forward" and "backward" flow mechanisms of portal hypertension. Relative contributions in the rat model of portal vein stenosis. AB - The contribution of "forward" and "backward" flow mechanisms to the increased portal pressure observed in the rat model of portal vein stenosis was evaluated using experimental and theoretical data. The experimental data indicate that portal venous inflow, portasystemic shunting, and portal venous pressure are increased after 10 days of portal vein stenosis when compared with sham-operated controls. Furthermore, portal vascular resistance was 40% higher in portal hypertensive animals than in control animals. The elevated portal vascular resistance in the rat with portal vein stenosis was attributed to the high resistance of the portal venous collaterals. Incorporation of the experimental data into a mathematical model that simulated the changes induced by chronic portal vein stenosis allowed for fractionation of the "forward" and "backward" flow components involved in the pathogenesis of portal hypertension. Model predictions indicate that the "forward" and "backward" flow mechanisms account for 40% and 60% of the increase in portal pressure, respectively. PMID- 4043667 TI - In vitro dissolution of cholesterol gallstones. A study of factors influencing rate and a comparison of solvents. AB - Models of the common bile duct and gallbladder were constructed to study conditions that affect the rate of cholesterol gallstone dissolution by monooctanoin and other potential solvents. In the bile duct model, the rate of monooctanoin infusion was not an important factor in accelerating dissolution time. In contrast, the exclusion of bile from interfering with solvent-stone contact or the enhancement of solvent-stone contact by stirring significantly accelerated stone dissolution. The combination of both bile exclusion and stirring increased the dissolution rate of gallstones by monooctanoin 15-fold. When compared with two other ethers and with monooctanoin, methyl tert-butyl ether was found to be the most potent gallstone solvent. Methyl tert-butyl ether completely dissolved 219-mg cholesterol stones within 60 min. In the gallbladder model, in the absence of stirring both methyl tert-butyl ether and monooctanoin floated on bile, whereas the gallstones sank resulting in minimal stone-solvent contact. To increase the stone-solvent contact, we used a pump to create sufficient turbulence to mix the solvent with bile. Pump stirring of monooctanoin in the presence of bile achieved rates of stone dissolution approaching that of stirred monooctanoin without bile. Stirring of methyl tert-butyl ether and bile, however, did not achieve sufficient solvent-stone contact to appreciably accelerate dissolution in the presence of 50% bile. Stone-solvent contact was a critical factor in determining the rate of gallstone dissolution in both gallbladder and common bile duct models. Efforts to enhance contact include bile exclusion and intraluminal stirring--both of which are clinically applicable. Methyl tert-butyl ether is a potent new cholesterol gallstone solvent with excellent potential for use in humans. Even with this potent agent, however, rapid gallstone dissolution is likely to require removal of most of the bile from the dissolution medium. PMID- 4043668 TI - Discordance of hepatitis B e antigen/antibody and hepatitis B virus deoxyribonucleic acid in serum. Analysis of 1063 specimens. AB - Hepatitis B virus DNA was determined in 1063 serum samples from 252 patients with hepatitis B surface antigen by the spot hybridization technique. The results were correlated with hepatitis B e antigen and antibody. Hepatitis B virus DNA was detected in 87% of hepatitis B e antigen-positive patients, in 18% of hepatitis B e antibody-positive patients, and in 18% of those negative for both. Discordance of antigen/antibody and hepatitis B virus DNA, i.e., the presence of the DNA in antibody-positive sera or the absence of the DNA in antigen-positive sera, was observed in 209 of 997 (21%) samples. Of 121 patients with histologic diagnosis, this discordance was observed in none of 20 patients with nonspecific changes, in 13% of 39 with chronic persistent hepatitis, in 21% of 38 with chronic active hepatitis, and in 38% of 24 with cirrhosis. Thus, hepatitis B e antigen/antibody testing alone failed to predict the presence or absence of circulating hepatitis B virion in a significant proportion of patients with advanced chronic liver disease. PMID- 4043670 TI - Successful endoscopic transection of a partially obstructing antral diaphragm. AB - A 14-yr-old girl presented with long-standing symptoms of partial gastric outlet obstruction due to an antral mucosal diaphragm that had a central aperture of 4-5 mm. The literature of this congenital malformation is reviewed with respect to diagnostic criteria and feasibility of endoscopic transection. The procedure and outcome of this first successful endoscopic transection of a partially obstructing antral diaphragm are reported. PMID- 4043669 TI - Increased type I procollagen mRNA levels and in vitro protein synthesis in the baboon model of chronic alcoholic liver disease. AB - We have investigated the molecular mechanisms responsible for the histologic changes induced by ethanol in the baboon model of alcoholic liver disease. Eleven ethanol-fed baboons and their pair-fed controls had histology evaluated and RNA extracted from percutaneous liver biopsy specimens. In 6 of the ethanol-fed animals, fatty liver developed, but no significant differences were found when the RNA from the control and ethanol-fed livers was translated in the reticulocyte lysate system or analyzed with specific cDNA probes. Five of the baboons given ethanol, however, developed significant fibrosis. Molecular evaluation revealed that the RNA from these livers was more active in in vitro protein synthesis, and the type I procollagen mRNA content was significantly higher per microgram of liver RNA as determined by hybridization analysis (183% +/- 23% SEM of control, p less than 0.02). In addition, there were higher levels of albumin mRNA content in the livers of ethanol-fed baboons that developed fibrosis (180% +/- 21% SEM of control, p less than 0.05). There was no change, however, in the levels of beta-actin mRNA, a representative constitutive protein. These findings in the baboon model of alcoholic fibrosis show that ethanol consumption increases type I procollagen mRNA, which may foster fibrogenesis; increases albumin mRNA content without causing an increase in serum albumin; and induces no change in levels of beta-actin mRNA. These studies also show that percutaneous needle biopsy can supply sufficient tissue to evaluate molecular changes in human liver disease. PMID- 4043671 TI - Colitis cystica profunda: presenting with complete intestinal obstruction and recurrence. AB - An unusual case of colitis cystica profunda is described. The patient presented with intestinal obstruction due to a polypoid mass in the descending colon, which was diagnosed as colitis cystica profunda after the patient underwent colectomy. Three other separate lesions were present in the ascending, transverse, and sigmoid colon. There was no antecedent or associated colonic disease. The disease recurred 1 yr later in the remaining colon and rectum. PMID- 4043672 TI - Fecal fat concentration. PMID- 4043673 TI - Changes in gastroenterology 1960-1985: lessons from the past and implications for the future. PMID- 4043674 TI - Lymph and blood capillaries of the human gastric mucosa. A morphologic basis for metastasis in early gastric carcinoma. AB - The distribution of lymph and blood capillaries has been studied by light and transmission electron microscopy in 16 endoscopic and surgical specimens of human gastric mucosa and submucosa. Four specimens were completely normal, seven showed mild gastritis, and five showed severe gastritis. On light microscopy, no definite distinction could be made between small mucosal lymph and blood capillaries. The distinction was achieved only by transmission electron microscopy where lymph capillaries could be identified by the presence of anchoring filaments and the demonstration of open gaps and overlapping endothelial cell processes, as well as by the absence of a basement membrane and "fenestrations" typical of the endothelial cells of blood capillaries. Although large lymph vessels were observed in the submucosa, lymph capillaries were found only in the deep lamina propria adjacent to and within the muscularis mucosae. The upper and middle levels of the lamina propria of the gastric mucosa contained no lymph capillaries. The entire mucosa showed a rich supply of blood capillaries, many of which were adjacent to the basal lamina of gastric glands and the surface epithelium. These morphologic findings correlate with clinicopathologic observations on early gastric cancer. The particularly low incidence of lymph node metastases in the subtype of early gastric cancer that remains confined to the mucosa may be explained by the rarity of lymph capillaries in the mucosa. The high percentage of blood-borne metastases in recurrent early gastric cancer may be related to the rich vascularity of gastric mucosa. PMID- 4043675 TI - Pancreas divisum: congenital anatomic variant or anomaly? Contribution of endoscopic retrograde dorsal pancreatography. AB - The relationship between pancreas divisum and pancreatic disease has been studied in a series of 304 patients. This congenital anatomic variant, consisting of a separate pancreatic ductal system, was diagnosed by endoscopic pancreatography and dorsal duct opacification was achieved in 97 of these patients. This anatomic variation was observed with the same frequency in cases of pancreatitis (acute and chronic) (6.9%) and in the series of patients investigated by endoscopic pancreatography taken as a whole (5.7%). Moreover, incidences of pancreatic disease in patients with and without pancreas divisum were not statistically different when compared. These results show that pancreas divisum should not be regarded as an etiologic factor in pancreatitis but should be considered as a coincidental anatomic variant encountered in nearly 10% of the population. The results obtained herein do not support the hypothesis that stenosis of the accessory papilla occurs frequently in cases of pancreas divisum. We conclude that no further therapy should be systematically proposed for patients with pancreas divisum and pancreatitis. PMID- 4043676 TI - Anorectal function in elderly patients with fecal impaction. AB - Manometric and other investigations were carried out in 55 elderly patients who had impacted masses of feces in the rectum upon admission to hospital and in 36 elderly age- and sex-matched control subjects. Maximum basal and maximum squeeze sphincter pressures in the patients were similar to those in the elderly controls. Most elderly patients in the impacted group and all control subjects were able to pass a 50-ml balloon from the rectum, although a lower proportion of patients, admitted with impaction, could expel a small solid sphere. In patients the rectum had to be distended with larger volumes than in controls before the presence of the rectal balloon, pain, and the desire to defecate were perceived and before rectal contractions were generated. Rectal pressures, recorded during rectal distention, were lower in the impacted group than in the control group. Finally, anal and perianal sensation was impaired in patients with fecal impaction. These findings are similar to those described in patients with low spinal cord injuries. PMID- 4043677 TI - Damage to the innervation of the pelvic floor musculature in chronic constipation. AB - Constipation and defecation straining have been implicated in the pathogenesis of anorectal incontinence. We have studied 24 women with chronic constipation and 20 age- and parity-matched control subjects. Electrophysiologic techniques were used to study the innervations of the puborectalis and external anal sphincter muscles. The results show that damage can occur to the nerve supply of both these muscles in chronic constipation, and that this probably is due to perineal descent during defecation straining. PMID- 4043678 TI - Studies of the antidiarrheal action of clonidine. Effects on motility and intestinal absorption. AB - Clonidine, an alpha 2-adrenergic agonist, has been reported to stimulate the rate of electrolyte absorption in vitro, to alter intestinal motility in vivo, and to have antidiarrheal effects in animals. Experiments were performed in 8 healthy volunteers in order to evaluate the antidiarrheal effect of clonidine in humans. When diarrhea was induced by intragastric infusion of 2700 ml of balanced electrolyte solution over 90 min, oral administration of 0.3 mg of clonidine reduced the volume of rectal effluent by 48% (from 1233 +/- 62 to 640 +/- 77 ml, p less than 0.001), a clear-cut antidiarrheal effect. Clonidine increased total gut volume significantly (from 987 +/- 91 to 1830 +/- 142 ml, p less than 0.001), suggesting that clonidine exerted its antidiarrheal effect by altering gut motility, i.e., increasing the capacity of the gut and slowing the transit of fluid through the intestine. In other experiments, the net absorption rate of the whole gut during steady state total gut perfusion was measured. The rate of absorption of fluid was transiently stimulated by clonidine by 15% (from 696 +/- 77 to 799 +/- 55 ml/h, p less than 0.02), indicating an additional effect on mucosal cell function. These studies indicate that in this experimental diarrhea model, clonidine has antidiarrheal properties that are due largely to effects on motility of the gut but that clonidine also modestly stimulates the net rate of absorption by intestinal mucosa. PMID- 4043679 TI - Effect of central sympathectomy on gastric and small intestinal myoelectric activity and plasma motilin concentrations in the dog. AB - Using a canine model, we studied fed and fasting gastric and small intestinal myoelectric activity and plasma motilin concentrations before and after transection of the spinal cord between the second and third thoracic segments. In sham-operated dogs, migrating complexes returned to normal by the second day after operation. Immediately after spinal cord transection, migrating complexes cycled in jejunum and ileum but not in the stomach and duodenum. After 11 and 15 days, migrating complexes returned to the duodenum and stomach, respectively. Plasma motilin concentrations did not cycle in animals without duodenal migrating complexes but returned to a normal cyclical pattern when duodenal migrating complexes returned. Feeding interrupted migrating complexes after cord transection and sham operation. The data observed in animals after 15 days suggest that myoelectric activity in fasted dogs and conversion of the fasted to the fed state of myoelectric activity are not under the control of supraspinal, sympathetic pathways. PMID- 4043681 TI - Presidential address 1985. The A/S/G/E--problems, progress, and promise. PMID- 4043680 TI - Gastrointestinal transit time in human pregnancy: prolongation in the second and third trimesters followed by postpartum normalization. AB - Fifty-nine studies of gastrointestinal transit time were performed in 27 healthy women during pregnancy and postpartum. Gastrointestinal transit time was defined as the time of the first sustained rise in breath hydrogen concentration after ingestion of 10 g of lactulose. Gastrointestinal transit time was significantly prolonged in both the second and third trimesters of pregnancy (125 +/- 48 min and 137 +/- 58 min, respectively) when compared with either the first trimester of pregnancy or the postpartum period (99 +/- 39 min and 75 +/- 33 min, respectively). Transit times measured in the first trimester were not significantly different from those postpartum. Because the prolongation of transit time in late pregnancy is transient, it is probably due to hormones (perhaps progesterone) or other metabolic effects of pregnancy. PMID- 4043682 TI - Short (35-cm) versus long (60-cm) flexible sigmoidoscopy: a comparison of findings and tolerance in asymptomatic patients screened for colorectal neoplasia. AB - The purpose of this study was to compare the utility of the 35-cm versus the 60 cm flexible sigmoidoscope in screening asymptomatic patients for colorectal neoplasia. Two hundred fifty-eight patients 45 years of age or older were examined in a randomized fashion with both the 35-cm and 60-cm instruments. Fifteen percent (39/258) of patients had a total of 50 polypoid lesions 3 mm or greater in diameter (including one carcinoma). Of all polypoid lesions, 76% were detected with the 35-cm instrument compared to 98% with the 60-cm sigmoidoscope. Eighty-four percent of all polyps occurred within the distal 35 cm of colon. The mean time required to complete the examination was significantly less with the 35 cm sigmoidoscope than with the 60-cm sigmoidoscope (2.5 vs. 5.7 min). Moderate to severe discomfort was experienced by 69% of patients with the 60-cm instrument compared to only 29% with the 35-cm sigmoidoscope. Seventy-two percent of patients preferred examination with the shorter instrument compared with 7% for the longer sigmoidoscope, while 21% of patients expressed no preference. The 35 cm flexible sigmoidoscope fulfills many criteria of an effective screening test for colorectal neoplasia including rapidity of examination, safety, good sensitivity, and excellent patient acceptance. PMID- 4043683 TI - Training for flexible sigmoidoscopy. AB - Three hundred twenty-six participants of five 1-day continuing medical education courses on flexible sigmoidoscopy were surveyed to determine their use of lower intestinal endoscopes and to identify how well the education trained them to use the flexible sigmoidoscope. The number of participants using a flexible sigmoidoscope and/or colonoscope increased after the course. About one half of the respondents went from no use of the flexible sigmoidoscope to using it. About one fifth of the respondents were not using a flexible sigmoidoscope after the course for various reasons. Most respondents used more than one instrument after the course, with the combination of the 60-cm flexible sigmoidoscope and the rigid sigmoidoscope being most popular. The overwhelming majority found the flexible sigmoidoscope to be either very easy to use or reasonably easy to use. Only one complication was reported. Most of the respondents had attended only this 1-day course, but one third had taken either other courses or had been supervised for several procedures. PMID- 4043684 TI - Nodular duodenitis in chronic maintenance hemodialysis patients. AB - A retrospective study of 138 cases of chronic hemodialysis between 1977 and 1982 were reviewed for endoscopic, radiographic, and histologic characteristics of duodenitis. Forty patients underwent upper gastrointestinal barium x-rays; 13 were found to have multiple duodenal bulb nodules and three of these patients had very prominent duodenal bulb folds. There were 42 patients on whom upper panendoscopy was performed, and multiple duodenal nodules were seen in 15 patients and thickened folds in three patients. There were five patients in whom nodules were seen only on endoscopy. The size of the nodules varied between 3 and 8 mm in diameter and mucosal folds between 4 and 8 mm. Duodenal mucosal hyperplasia with chronic inflammatory cell infiltrate was found on biopsy of the nodules in 12 cases, while three cases with nodules revealed blunted villous structure with chronic inflammatory cells. PMID- 4043685 TI - Endoscopic drainage of pancreatic pseudocysts. AB - Enlarging pancreatic pseudocysts, as well as those that develop complications such as bleeding, leak, infection, and intestinal or biliary obstruction, require treatment. This treatment is usually surgical and consists of internal or external drainage or, less commonly, excision. Transcutaneous aspiration with or without drain placement has also been reported. We describe four cases of endoscopic cystogastrostomy and cystoduodenostomy undertaken in high risk patients who had either failed previous surgery (two) or were initially refused surgery because of prohibitive operative risk (two). Technique, limitations, and potential use of this procedure are discussed. PMID- 4043686 TI - Multiquadrant precut papillotomy for extraction of large impacted common bile duct stone. PMID- 4043687 TI - ERCP and endoscopic sphincterotomy in patients with situs inversus. PMID- 4043688 TI - The use of dual percutaneous endoscopic gastrostomy (DPEG) in the management of chronic intermittent gastric volvulus. PMID- 4043689 TI - Hydrostatic dilation of upper gastrointestinal strictures with endoscopic control. PMID- 4043690 TI - Flexible fiberoptic sigmoidoscopy--longer may not be better for the "nonendoscopist". PMID- 4043691 TI - The systemic complications of sclerotherapy of esophageal varices. PMID- 4043692 TI - A method for maintaining patency of an intracholedochal stent. PMID- 4043693 TI - Pancreas divisum may be only coincidental. PMID- 4043694 TI - Retrieval of two intragastric rings by a novel approach. PMID- 4043696 TI - Percutaneous endoscopic gastrostomy. PMID- 4043695 TI - The double papilla of Vater. PMID- 4043697 TI - Removal of bezoars from stomach using an endoscopic drill. PMID- 4043698 TI - Changes of AChE activity in the nerves of pig ovaries in different periods of pregnancy. AB - The paper presents a description of morphologic features of AChE-positive nerves, and changes taking place in AChE activity in pig ovaries during different stages of pregnancy. 36 sows, pregnant for the first time, were used in the studies. The animals were divided into 5 groups: Group I embraced sows on 14th d of pregnancy (n = 7), group II: on 20th d (n = 6), group III: on 30th d (n = 7), group IV: on 60th d (n = 8), and group V on 90th d of pregnancy (n = 8). The animals were slaughtered and bled. Left-side ovaries were taken for histochemical studies, and right-side ones for biochemical analyses. AChE-positive nerves in the ovaries were discovered taking advantage of the method by KARNOVSKY and ROOTS. AChE activity was determined according to RUCKENBUSH and RUCKENBUSH after homogenization of whole ovaries. It was found that: Morphological picture of the AChE-positive nerves differed in particular stages of pregnancy, this being reflected--among others--in the presence of characteristic, "bead-like" nerve fibres in later period of pregnancy (on 30th, 60th, and 90th d); The highest activity of AChE was recorded on 20th and 30th d of pregnancy, the lowest on 13th d. PMID- 4043699 TI - [Interpretation of the organization of the aortic arch in the Dibamus (Reptilia, Squamates) using findings obtained from various groups of Squamates serpentiformes]. AB - The comparative study of the aortic trunks of Dibamus (subterranean limbless Squamate) and of the other Squamata shows the presence of an original vascular organization in the serpentiform animals submitted to the subterranean life constraints as Scolecophidia, Amphisbaenia, Dibamidae, Anniellidae, Feyliniidae, and some Scincidae (genus Acontias and Typhlosaurus). Nevertheless, the morphology of the systemic and carotidian trunks supplies only few informations on the phylogenetical status of Dibamus. PMID- 4043700 TI - Studies on orthocephalization. 8. Behaviour of the visceral part of the rat head in the period between 7 and 60 days after gestation. AB - The present paper considers the significance of interosseous flexions of the palatal complex in the process of orthocephalization of the rat skull between 7 and 60 d after birth. The study is based on a sample of 25 female rats who have been X-rayed at 7, 14, 30, and 60 d with subsequent analysis of the photographs obtained. During this period the constituents of the bony palate, i.e. the palatine bone, the palatal process of maxilla and the palatal part of premaxilla grow steadily but with decreasing rate of increase with age. The premaxilla grows the most, while the palatal bone grows the least. The angle between the cranial base and the palatal plane decreases, i.e. the rat skull becomes more orthocranial with age. At the same time, the palate becomes more orthopalatal, primarily by an increase in the angle between the palatine bone and maxilla. As the angle between the cranial base and the palatine bone after 14 d increases, i.e. rotates in the opposite direction of the palatal plane, it may be concluded that the process of orthocephalization in this period is caused by the deflexion of the angle between the palatine bone and maxilla, while it before 14 d is caused by a combination of an interosseous deflexion in the palate and an upwards rotation of the palatine bone relative to the cranial base. PMID- 4043701 TI - Studies on the participation of tunica albuginea and rete testis (TA and RT) in the quantitative structure of human testis. AB - In 309 testes, the % proportion of the tunica albuginea (TA) and rete testis (RT) was determined in the quantitative composition of the testis. The weight of the testis ranged widely from 3.0 to 34.5 g, mean weight 14.67 +/- 6.0 g, with a statistically non-significant difference in favour of the right testis (15.3 +/- 6.32 g). The mean weight of the testes decreased with age, being 16.77 g in young men, 14.98 g in middle-aged men, and 13.6 g in old men. The absolute weight of TA and RT ranged from 1.0 to 12.0 g, being on the average 3.57 +/- 1.42 g. Similarly as the mean weight of the testis, that of TA and RT was not significantly different between the right and left testis, and between various age groups. On the other hand, a significant rise was observed in the % proportion of the mass of TA and RT in the total mass of the testis in various age groups. In young men, this proportion was 20.36%, in middle-aged men 24.28%, and in old men 28.83%. Statistically significant differences appeared between the mean values in the youngest and oldest age groups and the oldest and middle age groups. In the whole material, the % proportion of TA and RT in the quantitative composition of the testis ranged from 13.6 to 75.0%, being 25.7 +/- 8.1% on the average. Identical results were obtained by 2 different methods in men dying between 17 and 91 a of age, and the mean age of them was 58.2 a. PMID- 4043702 TI - [The development of the clavicle in man]. AB - The development of the human clavicle was studied in 50 to 60 d old human embryos. Our findings are summarized as follows: The whole clavicle develops from a cartilaginous anlage. In the middle part of the clavicle, an osseus cuff develops very early by the ossification in the perichondrium. In the lumen of this cuff, a cartilaginous cork persists which is resorbed and replaced by bone and marrow later than in other bones. It is possible that cartilaginous nests may persist in the middle part of the clavicle. In both extremities of the clavicle, the normal enchondral ossification exists as it is described in other anlages. It is difficult to explicate the syndrome of the cleido-facial and cleido-cranial dysostoses only as disturbances of the endesmal ossification. PMID- 4043703 TI - [Procedures of local approximation for nonparametric estimation of unknown continuous functions from given measurements]. AB - There exists a lot of literature about the nonparametric estimation of unknown continuous functions from measured values. Many formulas of different shape were discussed. In this paper, we show that a great part of those formulas may be developed by using a uniformly mathematical principle which we name the local approximation by the least squares method. The knowledge of the principle enables one to develop new estimating formulas with special properties. The LOKONREG-, LOLINREG- and LOQUAREG-estimation are compared with each other by means of two biometric examples. PMID- 4043704 TI - [The effect of low blood pressure on venous function during and outside of pregnancy and therapeutic consequences]. AB - Orthostatic dysregulations occur ten times more frequently in gravidae with low blood pressure than in those in whom it is normal. This condition can result in a temporarily insufficient blood supply to the uterus and hence to the foetus. As a consequence, abortions, premature and abnormal births, and complications during labour and lying-in occur more frequently among hypotonic women. Pathophysiologically, orthostatic dysregulations are caused by large quantities of blood remaining in the peripheral veins. In this connection it is well known that the hormonal change-over during pregnancy reduces venous tone, thus causing venous return to the heart to deteriorate. It has not yet been investigated whether or respectively how low blood pressure in pregnant and non-pregnant women affects venous hemodynamics and what effect treatment with dihydroergotamine (DHE) has. In order to answer these questions the authors performed 240 venous function measurements in a total of 140 pregnant and non-pregnant, hypotonic and normotonic women. Using a simple, non-invasive photoplethysmographic method, light reflection rheography (LRR), a check was first made as to whether there are differences in venous pumping in non-pregnant hypotonic as opposed to normotonic women. In 20 normotonic subjects the delta R mean value for venous drainage was 165 mV, while in 20 hypotonic women it was only 114 mV (p less than 0.001). While, on the basis of a corresponding classification, all of the normotonic women were classified as having normal veins or merely slight venous insufficiency, 14 hypotonic women were found to have moderately severe or severe venous insufficiency (p less than 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4043705 TI - [Significance of trial vacuum extraction in the framework of obstetric surgery in vertex presentation]. AB - On the basis of a clinical study of 76 infants born by trial vacuum extraction from the pelvic inlet, 57 infants were examined retrospectively with regard to early and late morbidity after "successful" trial vacuum extraction. In 34 cases surgery was indicated because of fetal distress; in 23 children the operation was performed because of a standstill at the pelvic inlet. The results were compared with a group of infants delivered by vacuum and forceps extraction from the centre of the pelvis (or the pelvic floor) or cesarean section in consequence of fetal distress. The results indicate the high risk for children born by trial vacuum extraction, especially in cases of fetal distress. In addition to statistically significant lower Apgar scores and a statistically significant higher acidosis morbidity (p less than 0.05) as compared to other obstetric operations, there is also a statistically significant greater number of "striking" and "injured" children as opposed to those delivered by vacuum or forceps extraction from the centre of the pelvis (or the pelvic floor) or by cesarean section in consequence of fetal distress. These neurological deviations represent primarily the static-motoric and speech development, and are analogous to late morbidity after births from breech presentation. The findings confirm the clinical impression that trial vacuum extraction-especially in cases of fetal distress at the pelvic inlet-represent an additional risk to the child. In such cases cesarean section is the only alternative method of delivery. PMID- 4043706 TI - [Pattern changes in the framework of cesarean sections in 1980/83 as compared to 1974/76 in the University Women's Clinic in Jena]. AB - In a comparative study on Caesarean section problems-based on investigations from 1974/76 and 1980/83-conducted at the Gynaecological and Obstetrical Hospital of Jena University, changes are apparent in the indication for Caesarean section and in maternal morbidity. The evident decrease in statistically uncorrected perinatal mortality as well as in uncorrected intra-and postnatal mortality during this period (difference statistically significant at p less than 0.05) was not due to a further increase in Caesarean sections from 8.23% (period 1974/76) to 9.27% (period 1980/83), but to other factors (improved medical care for pregnant women and improved neonatal check-up). In comparison with uncorrected intra-and postnatal mortality, perinatal Caesarean section lethality even showed a 2,46-fold relative increase. As late morbidity among high-risk children related to the immediate stage of labour is still poorly understood, "extended" indication for Caesarean section is maintained-in spite of high infection morbidity among mothers. General perioperative antibiotic prophylaxis for these women is recommended because of the statistically significant poor situation of secondary Caesarean sections as far as maternal morbidity is concerned. PMID- 4043707 TI - [Rh-incompatibility acidosis in newborn infants following intrauterine transfusion]. AB - Severe foetal Rh erythroblastosis is treated by intrauterine transfusion, in most cases with ACD adenine erythrocyte concentrates. In two cases where delivery took place shortly after the last intrauterine transfusion, metabolic acidosis developed post partum, which could possibly be attributed to the erythrocyte concentrates in the transfusion. Multiple pH level measurements in the ACD adenine erythrocyte concentrates revealed pH levels between 6.4 and 6.8. Erythrocyte concentrates prepared with heparin showed pH levels between 7.18 and 7.25 and should therefore be used for intrauterine transfusion in place of ACD adenine erythrocyte concentrates. PMID- 4043708 TI - [In vitro test for the radioimmunological demonstration of the adsorption of maternal antibodies to placental basal membrane collagen]. AB - Polystyrene tubes were activated by adsorption of placental basement collagen (Type IV collagen). Binding of maternal immunoglobulin from serum samples to immobilized collagen was detected with 125I-labeled Antihuman IgG. An almost complete loss of binding resulted by adding solubilized Type IV collagen to the serum or pretreating the coated tubes with highly purified collagenase as well as using uncoated tubes. A high adsorption rate of IgG to Type IV collagen (2029 +/- 388 cpm) was detected in patients with moderate to severe gestosis (n = 16) (index greater than or equal to 4). 925 +/- 192 cpm were measured in mild gestosis (n = 13). Only 315 +/- 24 cpm could be detected in samples of a healthy control group (n = 17). A correlation was found between the index of gestosis and adsorption of maternal IgG to Type IV collagen (r = 0,823). It is concluded that the concentration and adsorption of immunoglobulins binding to basement membrane collagen is related to the severity of the disease and may play an important role in the development of symptoms of gestosis. PMID- 4043709 TI - [Fertility following function-preserving surgery in tubal pregnancy]. AB - In the last few years an obvious trend toward conservative technique in tubal surgery is observed. Likewise, at our institution, emphasis was placed on preservation of function, too. 59 patients received conservative surgery of tubal pregnancies between 1979 to 1982. 7 women were lost for follow-up. 28 patients showed further desire for child-bearing. 20 of them have had a subsequent intrauterine conception (71.4%), 11 women have had term pregnancies (39.3%). 3 patients were pregnant at time of investigation. The abortion rate was 17.8%. Recurrent ectopic pregnancies were found in 5 cases (9.5%). However, the operated fallopian tube was involved only in 3 cases (5.7%). In 26 cases the patency of the tubal lumen was examined by means of hysterosalpingography. 50% of those women had remained childless. The results of HSG showed a patent passage of the operated tube in 11 cases. Our results show a high rate of subsequent pregnancies and a rather low incidence of repeat ectopic pregnancies in cases of conservative surgery and justify our decision to save the involved tube whenever fertility is desired. PMID- 4043710 TI - [Urodynamic results before and after physiotherapy of women with stress incontinence]. AB - With reference to the urodynamic results in 21 women with mild stress incontinence who underwent conservative treatment with pelvic floor exercises over a period of three to six months prior to possible surgery, the author comments on the value of this therapy. At the time of follow-up examination 11 of the women were so satisfied with the regression of their complaints that surgery was unnecessary. Only two patients reported no change in their symptoms after treatment. It may be possible to use the parameters of urethrocystometry as an objective criterion of success; however, these are not statistically significant; they merely indicate a tendency to improvement. The results are discussed together with information given in the literature. PMID- 4043711 TI - [Preoperative cervix dilatation in 1st trimester pregnancy interruption using 9 deoxy-16, 16-dimethyl-9-methylene prostaglandin E2. A randomized double-blind study]. AB - In the double-blind study reported here the authors were able to confirm the time and dose-related effect of dilatation of the cervix by means of the new prostaglandin-E2 derivative (9-deoxo-16, 16-dimethyl-9-methylene-PG-E2-potassium salt) as compared to placebo. In spite of the short preoperative duration of action of three hours it was observed that half of the patients treated with the prostaglandin derivative vomited once or several times. The authors therefore consider that administration of the prostaglandin vaginal suppository is only justified in cases with a high risk of cervical injury, and in primiparae undergoing termination under local anesthesia. In 38 patients termination was performed by means of direct cervicomyometrial analgesia. With one exception they approved of chemical dilatation of the cervix in spite of the side-effects, assuming that it would result in less intraoperative pain. PMID- 4043712 TI - [Extraoral manifestation of a white sponge nevus of the mucosa]. AB - The nevus spongiosus albus mucosae (resp. white sponge nevus in the angloamerican literature) is a hereditary leukokeratosis localised preferably in the oral mucosa, but may simultaneously manifest itself in other regions, e.g. perianally. We report the case of a 18-year old patient with a primarily and exclusively extraorally located nevus spongiosus albus mucosae of the vulva. The differential diagnosis and clinical as well as therapeutical problems of this extremely rare disease are discussed. PMID- 4043713 TI - Ethanol potentiation of carbon tetrachloride hepatotoxicity: possible role for the in vivo inhibition of aldehyde dehydrogenase. AB - A potentiation of CCl4-induced hepatotoxicity was observed in rats pretreated with ethanol 18 hr prior to CCl4 exposure. Hepatic microsomal aldehyde dehydrogenase (ALDH) was significantly inhibited in animals sacrificed 1 hr following the sequential exposure, however, no more so than in those animals receiving CCl4 alone. The animals receiving ethanol alone had ALDH activity similar to vehicle treated controls. Twenty-four hours following a potentiating dose of ethanol and CCl4 an 81 and 57% decline in NAD+-dependent microsomal and mitochondrial ALDH activity was observed, respectively. Similar results were observed for microsomal and mitochondrial NADP+-dependent ALDH activity. The decline in membrane-bound ALDH was greater in potentiated animals than in those receiving CCl4 alone. A relatively smaller decline in cytosolic ALDH activity was observed in CCl4 treated rats with or without ethanol pre-exposure. The data suggest that inhibition of membrane bound ALDH may be one of the major mechanisms of in vivo potentiation of CCl4-induced hepatotoxicity by ethanol. PMID- 4043714 TI - Resolution of multiple P-450 forms: separation of aryl hydrocarbon hydroxylase and aminopyrine N-demethylase-associated P-450 isoenzymes by chromatofocusing. AB - Chromatofocusing between pH 7.4 and 5.0 was introduced as a final step for the resolution of multiple forms of cytochrome P-450 from control, phenobarbital and 3-methylcholanthrene-pretreated rat liver microsomal fractions. Altogether, chromatofocusing produced 21 P-450-containing pools, which differed from each other with respect to substrate specificity, spectral maximum and elution pH. Aryl hydrocarbon (benzo(a)pyrene) hydroxylase (AHH) activity was concentrated into low pI pools in all animal groups. 7-Ethoxycoumarin O-deethylase (ECOD) activity comigrated with AHH activity throughout the purification procedure. Aminopyrine N-demethylase (APND) activity was spread into several pools with forms of both low and high pI proteins. PMID- 4043715 TI - Examination of the bronchoconstrictor response of guinea-pig isolated lung to beta-phenylethylamine. AB - beta-Phenylethylamine (PEA) produced a contraction of the guinea-pig isolated lung parenchymal strip and bronchoconstriction of perfused lungs. Reserpine pretreatment had little effect on these responses indicating a substantial direct effect. Phentolamine (10(-6) and 10(-5) M) had minimal effect on PEA in the lung strip compared with that on noradrenaline, eliminating involvement of alpha adrenoceptors. PEA was unaffected by atropine (10(-7)M) or a mepyramine (10( 7)M); metiamide (10(-4)M) mixture. The contraction was not therefore mediated via muscarinic or histaminergic receptors. 5-HT and dopamine receptors were also discounted. Possible stimulation of a phenylethylaminergic receptor and its relevance to bronchial asthma is discussed. PMID- 4043716 TI - Gastrointestinal effects of the extracts of Rhigiocarya racemifera (Menispermaceae). AB - The gastrointestinal effects of the aqueous extract of Rhigiocarya racemifera was studied in rats and was compared with that of cimetidine. Ulcers were induced in rats by means of drugs: indomethacin, reserpine and serotonin and by shay rats. The extract was found to have significant (P less than 0.05) antiulcer activity against all the models studied. The LD50 was found to be 141.25 mg/kg body weight and ED50 16.5 mg/kg. Phytochemical studies revealed the presence of glycosides, saponins, and tanins. The extract does not show antimicrobial effects. PMID- 4043717 TI - Influence of phenoxybenzamine on the stereotyped behaviour induced by fencamfamine in rats: evidence for a qualitative alteration. AB - The interactions between norepinephrine (NE) and dopamine (DA) systems in mediating stereotyped behaviour induced by different doses of fencamfamine (1-30 mg/kg) were studied in male rats. Pretreatment with phenoxybenzamine (5.0 mg/kg) resulted in a significant leftward shift of the control curve for stereotypy. The qualitative analysis of the stereotyped behaviour parameters when compared to controls showed: higher rearing frequency at a dose of 3.0 mg/kg; lower locomotor activity at a dose of 6.0 mg/kg; higher licking and gnawing frequencies at a dose of 10.0 mg/kg. These findings indicate that the role of DA systems on the stereotyped behaviour induced by fencamfamine is dependent on the degree of NE transmission in the CNS. PMID- 4043718 TI - Differential biochemical and behavioral effects of single and chronic administration of amphetamine and apomorphine. AB - The single and repeated effects of apomorphine (AP) and amphetamine (AM) administrations were compared on rearing behaviour in an open field (RF) and on rearing stereotyped behaviour (RSB). Single AP treatment did not modify RSB while decreased the ability of low doses of AP to inhibit RF. Opposite data were observed after AM single administration. Repeated treatment with both drugs reduced the inhibitory effects of AP low doses on open field behaviour. The AP repeated administration enhanced the dihydroxyphenilacetic (DOPAC) and homovanilic acid (HVA) striatal levels while the same AM treatment was unable to affect the dopamine (DA) metabolites levels. Taken together, our results support the view that behavioural changes observed after AP single and repeated treatment are a result of DA autoreceptors subsensitivity. Nevertheless, the behavioural changes detected after AM treatments are probably related to mechanisms other than the development of DA autoreceptors subsensitivity. PMID- 4043719 TI - The effects of 11-ketotestosterone and testosterone on the skin structure of brown trout, Salmo trutta L. AB - 11-Ketotestosterone and testosterone were administered by intraperitoneal implants to immature brown trout. Physiological levels of circulating androgens were maintained over a period of 4 months and this resulted in changes in skin structure which resembled those occurring in maturing male brown trout. 11 Ketotestosterone promoted both epidermal and dermal thickening, and markedly reduced the number of superficial goblet cells, whereas testosterone stimulated only epidermal thickening. The relative roles of these two androgens in the normal maturational processes of brown trout are discussed. PMID- 4043720 TI - Retinal modulation of the hypothalamic sensitivity to testosterone feedback in photoperiodism of quail. AB - This experiment was performed on two groups of male Japanese quail. One had been maintained in our laboratory as a closed colony (S-group), and the other had been obtained from a commercial source (R-group). Different responses of gonadal function were found between two groups following either testosterone treatment or exposure to short days. Immature birds of these groups responded to long days with rapid gonadal growth, but after sexual maturity, exposure to short days for 3 weeks induced testicular atrophy only in S-group. Involvement of the feedback effect of androgen in the photoperiodic response was then examined. Under long day conditions, intraperitoneal placement of testosterone propionate (TP)-filled Silastic tube for 2 weeks decreased testicular weights in S-group but not in R group. Apparently, sensitivity to short days is closely correlated with sensitivity to testosterone in the adult male. By bilateral enucleation, quail of S-group became less sensitive to both gonad inhibitory effect of short days and the negative feedback effect of TP. These results suggest that the photoperiodic mechanisms that are primarily mediated by the retinal system play a role in altering sensitivity to steroid feedback at the hypothalamus. PMID- 4043721 TI - Serum progesterone, estradiol-17 beta, and glucocorticoids in the collared peccary during gestation and lactation as influenced by dietary protein and energy. AB - Sixteen pregnant collared peccaries were assigned to four experimental diets representing two levels of crude protein and two levels of digestible energy. Serum levels of progesterone, estradiol-17 beta (E2), and glucocorticoids were measured by radioimmunoassay. There was no significant dietary effect (P greater than 0.05) associated with any hormone during gestation. Progesterone did not differ between days 11 and 140 of gestation (X +/- SE = 36.48 +/- 1.11 ng/ml, N = 72), began to decline during the last week prepartum, and continued to decline within 24 hr of birth. Glucocorticoid concentrations remained level throughout gestation (X +/- SE = 6.57 +/- 0.45 microgram/dl, N = 74). E2 levels were low during the first 90 days of gestation, rose significantly (P less than 0.001) from 10.11 +/- 1.73 pg/ml (X +/- SE, N = 8) at Days 81-90 gestation to 49.07 +/- 12.87 pg/ml (N = 3) at 2-4 days prepartum (Days 141-147 of gestation), and declined rapidly to baseline levels within 24 hr of farrowing. Litter size had no effect on progesterone or E2 concentrations. There was no significant dietary effect on litter size or gestation length. During lactation, glucocorticoids and E2 remained stable and did not differ by diet, while progesterone concentrations appeared to be affected by diet. Individuals on the high energy-high protein diet returned to normal ovarian function before animals on the other three diets. Results indicated that the pregnant collared peccary can maintain a reproductive steroid environment that allows for fetal development in the face of moderate caloric or protein restriction and that the lactating peccary can undergo a postpartum ovulation in the presence of good nutrition. PMID- 4043723 TI - Avian renal responses to oxidized and nonoxidized bPTH(1-34). AB - The hypotensive, hypercalcemic, and hyperphosphaturic responses to bovine synthetic 1-34 amino acid parathyroid hormone [bPTH(1-34)] were simultaneously evaluated in anesthetized laying hens, and compared to the same responses to oxidized (0.3% hydrogen peroxide) bPTH(1-34) prepared from the same commercial batch of hormone. The oxidized and nonoxidized hormones were administered intravenously into separate groups of animals, which were also receiving a constant intravenous infusion of inulin and p-aminohippuric acid (PAH) to serve as renal clearance test markers. bPTH(1-34) caused a 33.25 +/- 7.05 mm Hg decrease in mean arterial blood pressure. The corresponding change in response to the oxidized hormone preparation was a 10.75 +/- 1.49 mm Hg decrease, a significant reduction in hypotensive activity compared to the intact hormone. In contrast, oxidation had no influence on the hypercalcemic or hyperphosphaturic (relative clearance of phosphate, CPO4/CIn) responses to bPTH(1-34), both preparations causing significant and parallel increases in these variables. Both hormone preparations also caused increases in urine flow rate, GFR, CPAH, CCa/CIn, CK/CIn, CNa/CIn, and urine pH. However, on the basis of percentage change from the respective control periods, only CNa/CIn and urine pH showed significant differences between the two hormone preparations, with the intact hormone causing greater natriuresis and urine alkalinization than the oxidized hormone. The failure of peroxide oxidation to significantly affect the renal hyperphosphaturic response to bPTH(1-34) in chickens contrasts with results reported on mammalian species, and may be related to differences in the mechanism of renal phosphate transport between these groups. PMID- 4043722 TI - Renal and cardiovascular effects of angiotensin II in the rainbow trout, Salmo gairdneri. AB - The renal and cardiovascular effects of an intravenous infusion of angiotensin II in the freshwater anaesthetised rainbow trout, Salmo gairdneri, have been reappraised, without the infusion of noradrenaline. In these fish the previously reported antidiuretic response to angiotensin II was not maintained although a systemic pressor response persisted and the tubular transport maximum for glucose remained depressed. The data suggest that angiotensin has an intrarenal action which may play a role in renal adaptation to increased environmental salinities. PMID- 4043724 TI - The influence of acute or repeated immobilization on plasma prolactin levels in the turkey (Meleagris gallopavo). AB - Three experiments were conducted to evaluate the effect of immobilization on plasma prolactin (PRL) levels in the immature turkey. Acute immobilization for 120 min resulted in elevated PRL levels (P less than 0.05) starting 15 min after the onset of immobilization. Release from immobilization caused PRL levels to return to those of the nonimmobilized controls by 120-180 min following replacement of the turkeys in cages. Repeated immobilization for 3 or 5 consecutive days diminished PRL response (P less than 0.05) to subsequent immobilization. It is suggested that the PRL controlling mechanism(s) of the young turkey is both susceptible and able to habituate to changes induced by immobilization stress. PMID- 4043725 TI - Circadian control of a daily rhythm in hemolymph ecdysteroid titer in the insect Rhodnius prolixus (Hemiptera). AB - The hemolymph levels of the insect molting hormone (ecdysteroid) during the week preceding ecdysis in fifth-instar male Rhodnius prolixus have been determined using a radioimmunoassay. When animals are kept on light-dark cycles, the titer displays massive daily increases and decreases producing a daily rhythm. This rhythm is maintained with a period of approximately 24 hr in continuous darkness. The free-running period of the rhythm was determined at 24 and 28 degrees and found to be temperature compensated. Therefore the titer of ecdysteroids is modulated by a circadian system. Since ecdysteroids are known to influence a wide variety of developmental events ranging from chromosome puffing to cuticle deposition, circadian modulation of the titer will provide information concerning time to all ecdysteroid sensitive tissues hence could function as a pacemaker for imposing developmental synchrony. PMID- 4043726 TI - Light and electron microscopic identification of gonadotrophic cells in the pituitary gland of the goldfish by means of immunocytochemistry. AB - Immunocytochemical techniques were used at the light and electron microscopical levels in order to localize and to characterize the gonadotrophs in the goldfish pituitary gland by means of antibodies to carp gonadotrophin (c-GTH) or its subunit (c-GTH beta). At the light microscopical level antibodies to c-GTH reacted weakly with cells located in the rostral pars distalis (RPD) and strongly with cells of the proximal pars distalis (PPD). The labeling was restricted to the proximal pars distalis when antibodies to c-GTH beta were employed. The PAP and colloidal-gold postembedding procedures demonstrated that two cell types of the PPD react with both immune sera. These cells correspond to the so-called globular and nonglobular basophils of the goldfish pituitary. The labeling was located over the small secretory granules and the large globules. A relationship was noted between the intensity of the labeling and the electron density of the globules. PMID- 4043727 TI - [Plasma levels, metabolic clearance rates, and rates of secretion of testosterone and estradiol-l7 beta in the silver eel (Anguilla anguilla L.)]. AB - Testosterone (T) and 17 beta-estradiol (E2) plasma levels and metabolic clearance rates (MCR) were measured to investigate their ovarian production in immature silver eel. The dynamics of T and E2 metabolism were studied in catheterized eels using single injections of 0.2 to 0.5 microCi 3H-labeled steroid. The distribution volumes, biological half-life and MCR of nonconjugated tracers were calculated on the basis of a two-compartment model. At the end of the experiments, radioactivity was measured in different organs and tissues to localize the site of T and E2 catabolism. The volume of the inner compartment was 3.4% for T and E2. The outer compartment was larger for T (6.4%) than that for E2 (4.3%). The biological half-life was three to four times shorter for T (14.5 hr) than that for E2 (48.5 hr). The MCR for T (1.71 ml/kg body wt/hr) was higher than for E2 (0.51 ml/kg body wt/hr). Plasma levels were determined, using radioimmunoassay, on samples taken before injections of radiolabeled steroid. Free or protein-bound hormone levels were 0.12 and 0.31 ng/ml for T and E2, respectively. Conjugated T and E2 levels were, respectively, 0.13 and 0.23 ng/ml. Production rates were determined as the product of the MCR and the plasma concentration of the nonconjugated hormone. No significant differences were observed between the production rates of T and E2 (0.24 ng/kg body wt/hr). The liver was the principal site of metabolism for both hormones, which were excreted via the enterohepatic route. E2 injection gave rise to no metabolite in the plasma whereas after T injection a metabolite was produced, the concentration of which increased as a function of time. Its chromatographic properties were different from that of E2 or androstenedione, suggesting that no significant peripheral aromatization or 17-oxidoreduction occurs in the immature silver eel. PMID- 4043728 TI - [Tryptophan operon of methylotrophic facultative Pseudomonas sp. M bacteria. I. Isolation and characterization of auxotrophic Trp-mutants]. AB - Eighteen auxotropic trp- mutants of the facultative methylotrophic bacteria Pseudomonas sp. M. induced by nitrosoguanidine were characterized. Trp- mutants were tested for a number of biochemical properties: the capacity to grow on tryptophan intermediates, their accumulation in growth medium and activities of key enzymes. The trpE, trpD, trpC, trpF, trpB and trpA mutants were identified. The trpDC121 mutant with a one-point mutation has been obtained. This mutation caused inactivation of two enzymes--anthranilate-5-phosphoribosyl transferase and indole-3-glycerophosphate synthase. Unusual trpA and trpB auxotrophs with TrpAB- phenotype were described. It may be concluded that this type of mutations cause loss of catalytic activity of a subunit of tryptophan synthase as well as its structural modification. As a result, no active tryptophan synthase complex is formed and hence, the activity of the opposite intact subunit is inhibited. PMID- 4043729 TI - [Cytogenetic characteristics of the cells of different organs in AKR mice during the development of transplanted lympholeukemia]. AB - The process of cell generalization of lymphatic leukemia transplanted clone of AKR mice was studied by the routine and differential methods of metaphase chromosome staining. In 99.5% cases, the cells have an additional small chromosome specific for this type of leukemia, the chromosome being comparable in size with 18-19 pairs of chromosomes of mouse karyotype. Generalization process within 7 days' experiment (from the moment of transplantation up to the moment of animals' death from lymphatic leukemia) appeared to be slower in thymus and bone marrow of AKR mice than in spleen, lymphatic nodes and liver of the same animals with nearly the same generalization rate. A change in the frequency of marked leukemic cells in various organs at different time intervals after transplantation of lymphatic leukemia correlated with intensive cell division of an undulating character in all organs. The data obtained show that hyperdiploid cells carrying the specific additional small chromosome are responsible for the generalization process, this chromosome being also present in spontaneous strain of AKR mice, from which this clone was obtained. PMID- 4043730 TI - [Frequency of acrocentric chromosome associations in human blood lymphocytes when using different methods for its assessment]. AB - The indeces of frequency of associations of acrocentric chromosomes in lymphocytes of human peripheral blood were compared with the help of different criteria of their estimation: by argentofile connections and by specific location of acrocentrics in metaphase plate. It was shown by the methods of variation statistics that the specificity of orientation of associative acrocentric chromosomes towards each other by short arms to the distance equal to the length of G-chromosome long arm is not accidental. Therefore, the method elaborated on the basis of the estimation criteria reflects participation of acrocentric chromosomes association in the formation of general nucleus in interphase more completely than the Ag-method, as preservation of Ag-material depends on the extent of its resorbtion in mitosis. PMID- 4043731 TI - [Genetic aspects of the reactions of humoral immunity to collagen in man and animals. II. Modifications of the autoimmune status to collagen type I in NZB x NZW (F1) mice by sex hormones during ontogeny]. AB - The sex hormones, estradiol and testosterone, are able to modulate the status of spontaneous reactions of humoral immunity to type I collagen in ontogenesis of NZB x NZW (F1) females. Administration of estradiol to puber and unpuber females leads to a significant increase in the reactivity levels. The autoimmune status to type I collagen in NZB x NZW (F1) males is nonreactive to sex hormones influence. The results obtained corroborate the suggestion of the important role of sex hormones in formation of sex dimorphism and age variability to autoimmunity to type I collagen. PMID- 4043732 TI - Tubulin genes of the African trypanosome Trypanosoma brucei rhodesiense:nucleotide sequence of a 3.7-kb fragment containing genes for alpha and beta tubulins. AB - Most tubulin genes of the African trypanosome Trypanosoma rhodesiense are contained in 3.7-kb tandemly repeating units. One member of the 3.7-kb repeat family has been isolated from a T. rhodesiense genomic library, cloned, and sequenced. The 3646-bp fragment contains a complete alpha-tubulin gene and portions of two beta-tubulin genes. No introns are present. The genes are separated by 634- and 333-bp intergenic regions, which lack typical eukaryotic promoter and poly(A) signal sequences. However, both intergenic regions exhibit some structural similarity with sequences proposed to be involved in transcription termination and poly(A) addition in yeast. The 634-bp intergenic region shows homology to the "mini-exon" sequence associated with variable surface glycoprotein (VSG) and other trypanosome mRNAs. A comparable sequence is not found in the 333-bp intergenic region. T. rhodesiense alpha and beta-tubulins exhibit about 84-85% amino acid (aa) sequence homology with tubulins of mammals; the genes show about 74-75% nucleotide sequence homology. The alpha-tubulin contains 451 aa and the beta tubulin 442 aa; both have tyrosine as the C-terminal aa. PMID- 4043733 TI - An erythromycin-resistance gene from an erythromycin-producing strain of Arthrobacter sp. AB - A gene (ermA) coding for a presumed erythromycin-resistance (ErR) determinant from an Er-producing Arthrobacter sp. strain (NRRLB3381) was isolated from a gene bank in phage vector lambda 2001 by probing with a Streptomyces ErR gene. Strongly hybridizing fragments were subcloned and the appropriate segments sequenced. The ermA gene is 76 mol% G + C in content and specifies a protein of 340 aa with an Mr of 37454. S1 nuclease mapping and primer extension identified the putative promoter, which resembles the consensus sequence of Escherichia coli promoters particularly in the -10 region. A potential ribosome-binding site (RBS) (AGGAG) was also located. Unexpectedly, the majority of in vivo ermA transcripts detected were only 245 nt long, suggesting that expression of ErR may be regulated post-transcriptionally. Substantial homology is observed between the predicted aa sequences of the ermA-coded protein and the products of three other ErR determinants, from organisms that do not produce Er. PMID- 4043735 TI - Diagnostic dilemmas of confusion. Interview by Richard L. Peck. PMID- 4043734 TI - Polyadenylation of a human mitochondrial ribosomal RNA transcript detected by molecular cloning. AB - We have identified by molecular cloning a polyadenylated RNA transcript in the human leukemia cell line, K562, which is complementary to a portion of the gene encoding mitochondrial 16S ribosomal RNA (mt 16S rRNA). The cloned portion of the transcript corresponds to positions 2191-2395 of the human mt genome. The clone represents a cDNA copy of an RNA transcript from the H strand and carries an additional poly(A) tail 21 residues long at its 3'-end. Our data provide direct evidence for polyadenylation of some mt 16S rRNA transcripts. PMID- 4043736 TI - OTC misuse: worth the physician's attention. PMID- 4043737 TI - Headaches in older patients: Ddx and Tx of vascular and inflammatory pain. AB - Caution must be used in the elderly in making the diagnosis of complicated migraine, since transient ischemic attacks (TIAs), other cerebrovascular dysfunction, or structural lesions also can produce prolonged neurologic deficits with headache. Although hypertensive headache itself has no specific diagnostic features, patients who do complain of headache with episodes of hypertension usually localize the pain to the occipital region. This headache is most pronounced on awakening in the morning, usually diminishing 2 to 3 hours after arising. PMID- 4043738 TI - Diagnosis of noncardiac chest pain in older patients. AB - Barium swallow and gallbladder study may reveal esophageal or gastric cancer, esophageal or duodenal ulcer, or gallstones. If serious GI tract disorders such as these are ruled out, the next step is to seek an esophageal source of recurring chest pain. Intraesophageal acid infusion and edrophonium chloride (Tensilon) stimulation can be used in the office to reproduce chest pain secondary to an esophageal disorder. With either test, reproduction of the patient's typical chest pain is positive. About one-third of patients seen in our laboratory with noncardiac chest pain have a positive response. PMID- 4043739 TI - Why having older diabetics self-monitor blood sugars pays off. AB - By providing immediate positive rewards for actions that retard hyperglycemia, self-monitoring can reinforce patients' incentive to stick to their diets. This gives them a feeling of more control and satisfaction with the changes they make. Among 100 patients treated by a diabetologist, 70% were interested in home blood sugar monitoring techniques for better management of blood sugars, including more than one-half of all type II patients. PMID- 4043740 TI - Pacemakers: abnormal function. AB - Although intermittent or total loss of capture may occur at any time following pacemaker implantation, the peak incidence is either very early (less than 4 weeks) or very late (more than 3 years) in the life of the device. Oversensing may be a cause of recurrent syncope in patients who, during routine office visit testing, appear to have normally functioning pacemakers. PMID- 4043741 TI - [Use of a method of accelerated hygienic standardization for the chemical content in reservoir water exemplified by adipic and sebacic acids]. PMID- 4043742 TI - [Establishing methodological approaches to the hygienic evaluation of water soluble polymers used in hydrogeology]. PMID- 4043743 TI - [Toxicological and hygienic characteristics of benzyl acetate]. PMID- 4043744 TI - [Effect of substances released by polymeric material on the body of animals from the viewpoint of age]. PMID- 4043745 TI - [Assessment of the mutagenic hazards of benzene and its derivatives]. PMID- 4043746 TI - [Experimental study of the toxicodynamics of parachlorobenzotrifluoride]. PMID- 4043747 TI - [Modifying action of carbon tetrachloride on the cytogenetic effect of cyclophosphamide]. PMID- 4043748 TI - [Late effects of exposure to hexi- and trivalent chromium in water on the body]. PMID- 4043749 TI - [Food stimulation of the detoxifying system of the liver in preventing pesticide poisonings]. PMID- 4043750 TI - [Factors in the body adaptation of adolescents to working conditions during training in vocational and technical schools]. PMID- 4043751 TI - [New approaches in the hygienic evaluation of work loads of schoolchildren]. PMID- 4043752 TI - [Body function potentials of young schoolchildren as a criterion of physical load]. PMID- 4043753 TI - [Improved methodological protocol for the hygienic study of ion-exchange resins intended for drinking water treatment]. PMID- 4043754 TI - [Method of studying the atherogenic action of metals by using carbon-labelled cholesterol]. PMID- 4043755 TI - [Evaluation of the combined action of atmospheric pollutants in planning and implementing air protection measures]. PMID- 4043756 TI - [Characteristics of modelling the toxicokinetics of chromium and manganese]. PMID- 4043757 TI - [Hygienic evaluation of the technology for dry coke quenching in coke chemical plants]. PMID- 4043758 TI - [Hygienic principles of organizing the targeted physical education of pupils in 1 year vocational and technical schools]. PMID- 4043759 TI - [Determination of the risk of development of respiratory diseases in children exposed to chemical pollution of the atmosphere]. PMID- 4043760 TI - [Radon release from construction materials in housing]. PMID- 4043761 TI - [Establishment of the maximum permissible concentration of meliorant dust in the atmosphere]. PMID- 4043762 TI - [Experimental data on establishing the maximum permissible concentration of iron and its compounds in the atmosphere]. PMID- 4043763 TI - [Comparative hygienic characteristics of the working conditions in carpet factories located in different climatic zones]. PMID- 4043764 TI - [Analysis of the organ-tissue and intersystemic predominance of the localization of the pathology in body exposure to harmful chemical factors]. PMID- 4043765 TI - [Experimental research on the biological action of benzyl alcohol]. PMID- 4043766 TI - [Effect of elevated air pressure on the development of silicosis]. PMID- 4043767 TI - [Body function of workers operating different types of plasma units]. PMID- 4043768 TI - [Effect of the prework period on adaptive and compensatory indices of scientific researchers]. PMID- 4043769 TI - [Effect of Ciodrin residues on poultry products]. PMID- 4043770 TI - [Carcinogenic and mutagenic properties of the herbicide sencor]. PMID- 4043771 TI - [Further improvement of work with young scientists]. PMID- 4043772 TI - [Various components of bronchial secretion in dust-induced lung diseases]. PMID- 4043773 TI - [Clinico-functional characteristics of the bronchopulmonary system in workers exposed to low levels (MPEL) of asbestos-containing dust]. PMID- 4043774 TI - [Pathophysiological aspects of the development of diseases of the upper respiratory tract in workers in the asbestos-technological industry]. PMID- 4043775 TI - [Cerebral angiodystonia syndrome in the clinical picture of vibration disease]. PMID- 4043776 TI - [Effect of impulse local vibration with different time distribution of impulses on the body]. PMID- 4043777 TI - [Changes in the rate of conduction of stimulation in the motor fibers of the peripheral nerves in vibration disease]. PMID- 4043778 TI - [Evaluation of the local effect of the magnetic field on the human body in laboratory studies]. PMID- 4043779 TI - [Various physiological indicators in antenna operators of transmitting and receiving SW radio centers]. PMID- 4043780 TI - [Arteriosclerosis and arterial hypertension at remote periods after chronic carbon disulfide poisoning]. PMID- 4043781 TI - [Hygienic evaluation of microclimate in plastics molding plants]. PMID- 4043782 TI - [Effect of the level of general physical work capacity on various indicators of lipid and carbohydrate metabolism in persons with low professional motor activity]. PMID- 4043783 TI - [Activities of the Komsomol organizations with regard to implementing decisions of the Party and Government on the development of medical science and public health]. PMID- 4043784 TI - [Toxicological-hygienic characteristics of isopropyl alcohol]. PMID- 4043785 TI - [Role of the cesarean section in labor in parturients after treatment of infertility and inability to carry pregnancy to term]. PMID- 4043786 TI - [Changes in the prolactin level in the serum of the umbilical cord and peripheral blood collected during the first hour of life from newborn infants delivered by cesarean section]. PMID- 4043787 TI - [Evaluation of the condition of newborn infants delivered by obstetrical forceps and vacuum extraction]. PMID- 4043789 TI - [Effect of physical exertion during labor on the morphological picture and protein level in the blood of parturients]. PMID- 4043788 TI - [Copper, zinc and magnesium levels in placental tissue in early pregnancy and in at-term and prolonged pregnancies]. PMID- 4043790 TI - [Hysterosalpingography in a case of extensive damage of the external os and marked dilatation of the cervical canal]. PMID- 4043791 TI - [Circumvaginal muscles in sexual reactions of women]. PMID- 4043792 TI - [Crossed displacement of the kidney as a cause of anuria in pregnancy]. PMID- 4043793 TI - [Carcinoid tumor of the appendix with a metastatic focus in the parametrium]. PMID- 4043794 TI - [Indications for cesarean section in multiple pregnancy]. PMID- 4043795 TI - [Clinical aspects of septic conditions in women after cesarean sections]. PMID- 4043796 TI - [Morphological changes in the kidneys of female rabbits with experimental hypertension in pregnancy]. PMID- 4043798 TI - [Selected problems of morphology of the venous system of female internal genital organs. I. The system of uterine and ovarian veins]. PMID- 4043797 TI - [Prolactin and estradiol levels during hormone therapy of breast cancer]. PMID- 4043799 TI - [Selected elements of exertion physiology as an introduction to physiopathology in obstetrics and perinatology. II. Factors of physiological regulation of energy metabolism during physical exertion. Participation of energy substrates in exertion metabolism]. PMID- 4043800 TI - [Evaluation of the status of iron metabolism in women in the 20th and 36th weeks of pregnancy]. PMID- 4043801 TI - [Method of management of premature labor in twin pregnancies using glucocorticoids]. PMID- 4043802 TI - [Hysterographic findings in patients with cancer of the uterus and their prognostic significance]. PMID- 4043803 TI - [A case of cervical pregnancy in the second trimester complicated by placenta accreta]. PMID- 4043804 TI - [Pulmonary resection in children with chronic nonspecific diseases]. PMID- 4043805 TI - [Muscular thoracoplasty in pleural empyema]. PMID- 4043806 TI - [Combined surgery in cancer of the lung]. PMID- 4043807 TI - [Treatment of pleural empyema]. PMID- 4043808 TI - [Prevention and treatment of blood coagulation disorders after lung surgery]. PMID- 4043809 TI - [Metabolic status of peripheral blood cells according to phases of volemic disorders in patients with suppurative diseases of the lungs and pleura]. PMID- 4043810 TI - [Features of compensation of external respiratory function in children in the immediate period following pulmonary resection]. PMID- 4043811 TI - [Early diagnosis and surgical treatment of clotted hemothorax]. PMID- 4043812 TI - [Pathogenesis, diagnosis and treatment of postoperative intrapleural hemorrhages in patients subjected to surgery for tuberculosis and other pulmonary pathology]. PMID- 4043813 TI - [Classification of postoperative complications in pulmonary surgery]. PMID- 4043814 TI - [Surgical correction of transposition of the great vessels]. PMID- 4043815 TI - [Therapeutic tactics in wounds of the heart]. PMID- 4043816 TI - [Importance of protection of the ischemized myocardium in preventing acute myocardial insufficiency]. PMID- 4043817 TI - [Endoscopic diagnosis of the incomplete form of atrioventricular canal]. PMID- 4043818 TI - [Calculation of the diameter of the pulmonary arteries in tetralogy of Fallot]. PMID- 4043819 TI - [New methods in the complex treatment of suppurative-destructive diseases of the lungs and pleura]. PMID- 4043820 TI - [Effect of pulmonary artery embolism on hemodynamics of the pulmonary circulation]. PMID- 4043821 TI - [Current problems in the conservative treatment of chemical burns of the esophagus]. PMID- 4043822 TI - [Catamenial pneumothorax]. PMID- 4043823 TI - Neonatal outcome of infants delivered at 26-28 weeks of gestation. AB - The delivery results of 42 infants born to 40 mothers at the gestational age of 26-28 weeks during a period of 5 years were analyzed. The study was evaluated in two periods of time: in the first period out of 15 infants born only 5 (33.3%) survived, while in the second period 21 (77.7%) out of 27 infants survived (p less than 0.01). 38 infants were transferred to a neonatal intensive care unit for premature infants. Only 41% of the infants transferred in the first period survived, as compared to 80.7% of those transferred during the second period (p less than 0.01). There was no significant difference in the mean birth weight at each gestational age between the survivors and those who subsequently died in both periods of the study. In the study groups, cesarean section rate rose from 13.3% in the first period to 44% in the second. Mode of delivery, regardless of the presenting part, did not seem to influence neonatal survival. Obstetrical management, including the performance of operative delivery for fetal indications and active neonatal resuscitation, seems to be reasonable for infants at the gestational age of 26 weeks or more. PMID- 4043825 TI - Regulation of blood coagulation and thrombosis. AB - The syndrome of the hereditary tendency to venous thrombosis or thrombophilia has been recognized only after the discovery of regulatory mechanisms of the haemostatic system. At present, several distinct defects are known as causes of this syndrome: antithrombin III deficiency, protein C deficiency, protein S deficiency, dysfibrinogenaemia and dysplasminogenaemia. It is likely that several additional defects will be found in the near future. Consequently, it is important that a family history be taken in all cases of 'spontaneous' venous thrombosis and that laboratory studies be done to identify any underlying defect in the regulation of the blood coagulation system. We present preliminary data, which suggest that the incidence of the thrombophilia syndrome is higher than that of the haemophilias. PMID- 4043824 TI - 'False' fetal heart rate recording caused by interaction of an infusion pump and a fetal monitor. AB - The authors describe 4 cases of falsely recorded fetal heart rate pattern due to technical failure. Interaction of a fetal monitor and an infusion pump may lead to a 'false' fetal heart rate tracing, suggesting fetal compromise and masking the actual cardiac activity. The limits of indirect fetal monitoring are stressed. PMID- 4043826 TI - Delayed fibrinolysis: a cause of thrombosis? AB - On a theoretical basis, delayed fibrinolysis has always been assumed to allow a harmless, or rather, useful clotting process to develop into manifest thrombosis. Since the early sixties, when most modern concepts on fibrinolysis were postulated, the evidence for a causal relationship between impaired fibrinolysis and venous thrombosis has not become much stronger. On the other hand, several observations indicate an association between impaired fibrinolysis and arterial thrombosis. Recent years have witnessed a flare-up of interest in fibrinolytic therapy, especially of acute coronary artery thrombosis, and thanks to the availability of human tissue-type plasminogen activator, expansion of its field of application is to be expected. However, with drugs for maintenance enhancement of fibrinolysis still being out of reach, we rely on the well-established oral anticoagulant regimen for the prophylaxis of thrombosis in patients with an obvious thrombotic disposition. PMID- 4043827 TI - The mechanism of action of oral anticoagulants and its consequences for the practice of oral anticoagulation. AB - A short review on the discovery of the relation between vitamin K and the synthesis of clotting factors and on the development of anticoagulant therapy is given. The procoagulant activity induced by vitamin K resides in the postribosomal modification of N-terminal glutamic acids in gamma-COOH glutamic acids. The mode of action of oral anticoagulants is explained. The concentration effect relations and the choice of an oral anticoagulant is discussed. PMID- 4043828 TI - Standardization of the prothrombin time in oral anticoagulant control. AB - The establishment of International Reference Preparations for thromboplastin together with a recommended methodology for use has permitted the definition of a universal scale for intensity of oral anticoagulation. This scale is called International Normalized Ratio (INR). INRs can be calculated by using calibrated thromboplastin/instrument systems. A calibration model has been developed together with statistical methods to test this model. The imprecision of calculated INRs has been estimated using information from international collaborative studies and proficiency testing programs. Normalized prothrombin times obtained with calibrated thromboplastin/instrument systems have been shown to provide safe patient care in clinical practice. The development of control plasmas with assigned INR equivalents will complete the standardization system. The INR scale will facilitate the process of consensus-making with respect to optimal therapeutic ranges for anticoagulant intensity. Finally, it will improve the continuity of anticoagulant control of travelling patients. PMID- 4043829 TI - The management of stroke: fears and facts. AB - The poor definition of stroke, the lack of exact knowledge of its aetiology and natural history, particularly in an individual case, and our limited insights into the effects of both medical and surgical treatment have up to now not broadened the fairly narrow rational basis for management of stroke patients. It is argued that, despite a vast literature on the subject, treatment is mainly conducted along emotional lines in practice. The only exception to this forms the secondary prevention of cardiogenic emboli. PMID- 4043830 TI - Optimal therapeutic anticoagulation. AB - The relevant literature on the intensity of anticoagulation needed to prevent the development or growth of thrombi in patients at risk is reviewed. In case of elective surgery, prevention of venous thrombosis is easily attained with heparin or with coumarin alone, at levels of anticoagulation involving only a minor risk of bleeding complications. For posttraumatic prophylaxis, more intensive oral anticoagulation is required, similar to that for the management of active venous thrombosis, for which a combined heparin/coumarin regimen is proposed. A 90% reduction of the incidence of systemic emboli in patients with a high risk of developing intracardiac thrombosis requires high-intensity treatment with a target INR of 4. More intensive anticoagulation would be needed to obtain the same 90% protection in case of arterial (coronary) thrombosis. This is prohibited, however, by the rapidly increasing bleeding risk in cases with INR values greater than 5. With a target INR of 3.5 (sixty-Plus patients), the reinfarction rate will not be lowered by more than two thirds. Antiplatelet drugs given alone or in combination with anticoagulants have not been convincingly successful thus far in the prevention and treatment of thrombosis. PMID- 4043831 TI - [Rehabilitation of burn patients using pressure garments]. PMID- 4043833 TI - [A neuropsychiatric syndrome as the first manifestation of thyroid storm]. PMID- 4043832 TI - [Increasing incidence of pseudomembranous colitis and its association with antibiotic therapy]. PMID- 4043834 TI - [Differential diagnosis of a cervical mass]. PMID- 4043835 TI - [Pathologic aerophagia in childhood]. PMID- 4043836 TI - [Erythema nodosum due to disopyramide]. PMID- 4043837 TI - [Intramuscular myxoma associated with fibrous dysplasia of adjacent bone]. PMID- 4043838 TI - [Spontaneous antibodies to the insulin receptor]. PMID- 4043839 TI - [Endotracheal drug administration]. PMID- 4043841 TI - [Prognostic and diagnostic values of exercise stress in asymptomatic subjects]. PMID- 4043840 TI - [Premature rupture of membranes: review and update]. PMID- 4043842 TI - [Therapy with monoclonal antibodies]. PMID- 4043843 TI - [Periurethral teflon injection for urinary incontinence]. PMID- 4043844 TI - [Ranitidine or cimetidine]. PMID- 4043845 TI - [Cardiovascular effects of psychotropic drugs]. PMID- 4043846 TI - [Local hyperthermia for the treatment of deep-seated tumors]. PMID- 4043847 TI - [Predicted need for renal dialysis in Israel]. PMID- 4043848 TI - [Pacemakers implantation in children]. PMID- 4043849 TI - [A screening clinic for gynecological neoplasms]. PMID- 4043850 TI - [Fever as the only manifestation of recurrent familial Mediterranean fever]. PMID- 4043851 TI - [Subendocardial myocardial infarction after intravenous fluorescein]. PMID- 4043852 TI - [Angiolymphoid hyperplasia with eosinophilia]. PMID- 4043853 TI - [Early endoscopic sphincterotomy after cholecystectomy with T-tube drainage]. PMID- 4043854 TI - [Obstructive uropathy due to mumps]. PMID- 4043855 TI - [Contrast nephropathy]. PMID- 4043856 TI - [Non-Compliance with drug therapy]. PMID- 4043857 TI - [Breast pain: clinical significance and treatment]. PMID- 4043858 TI - [Evaluation of 1982/83 internship program by graduates of four medical schools in Israel]. PMID- 4043859 TI - [Pancreatic ascites]. PMID- 4043860 TI - [The experimental use of naloxone in the management of shock]. PMID- 4043861 TI - [Anaerobic bacterial infections]. PMID- 4043862 TI - [Anti-anaerobic antibiotic agents]. PMID- 4043863 TI - Contribution to the question of relationships between Enterobius vermicularis (L.) and inflammatory processes in the appendix. AB - We evaluated a bioptic material of appendices from the hospital in Ceske Budejovice, obtained from 1977-1981. Of these, 2173 appendices were removed as cases of a clinical appendicitis, 788 for preventive reasons. In the cases of a clinical appendicitis with the incidence of pin worms in the appendix, the histological picture displayed significantly more chronical, inflammatory changes than in acute cases (test chi 2), while in cases of a clinical appendicitis without the presence of pin worms, we found more acute than chronical forms of inflammations. Our results are supported also by an analysis of preventively removed appendices, where again more chronical, inflammatory changes were found in appendices with pin worms. PMID- 4043864 TI - Aminopeptidase inhibitor from Ascaris suum. AB - The correlation of aminopeptidase activity in the homogenate and perienteric fluid from Ascaris suum to the concentration of the studied fluids was assessed. The obtained non-linear correlations were interpreted as a result of the presence of the inhibitor. In further experiments, it was demonstrated that aminopeptidase inhibitor is present in the homogenate and perienteric fluid from A. suum. The effect of this inhibitor was studied using different substrates. The effects of the inhibitor on aminopeptidase activity of A. suum homogenate and on that of rabbit serum were studied. In other experiments it was found that an excess of the substrate impairs the effect of the inhibitor. PMID- 4043865 TI - The efficacy of Bacillus thuringiensis var. israelensis against larvae of the blackfly Odagmia ornata (Meig.) (Simuliidae) at low temperatures. AB - The effect of the suspension of Bacillus thuringiensis var. israelensis spores on larvae of the blackfly Odagmia ornata was studied in the laboratory and under field conditions of a natural biotope in southern Bohemia. The preparation Moskitur was used and its effect was tested in laboratory at temperatures 0.1-2.9 degrees C and 17-19 degrees C. Although O. ornata larvae were able to filter feed on a lethal dose of the preparation even at a lower temperature than 2.9 degrees C, no marked manifestation of mortality was observed at low temperatures in comparison with a control sample. PMID- 4043866 TI - [Anti-platelet actions of salicylates: in vivo, ex vivo and in vitro effects of choline salicylate]. AB - Effects of choline salicylate, sodium salicylate, choline chloride and acetylsalicylic acid on platelet aggregation in vivo, ex vivo and in vitro in mice were studied. These drugs all inhibited adenosine diphosphate (ADP)-induced respiratory depression, which is closely related to platelet aggregation in vivo, with choline salicylate showing the strongest inhibitory effect. Choline salicylate had a tendency to reduce the mortality of animals injected intravenously with endotoxin, but the other drugs had no such effect. The inhibitory effects of these drugs on ADP-induced platelet aggregation ex vivo were in the order of choline salicylate greater than acetylsalicylic acid congruent to sodium salicylate greater than choline chloride congruent to no effect, and plasma concentrations of protein-unbound salicylic acid at 1 hr after oral administration of drugs were in the order of choline salicylate greater than acetylsalicylic acid congruent to sodium salicylate. The in vitro effects of these drugs were in the order of choline salicylate congruent to sodium salicylate greater than choline chloride congruent to acetylsalicylic acid congruent to no effect. Therefore, it was considered that salicylic acid played an important role on the in vivo, ex vivo and in vitro effects of choline salicylate and that choline increased plasma concentrations of salicylic acid and consequently enhanced the in vivo and ex vivo effects of salicylic acid. Furthermore, the ex vivo effects of choline salicylate were found when ADP induced platelet aggregation was measured with platelet-rich plasma prepared from blood collected with heparin as anti-coagulant, but not when blood was collected with citrate.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4043867 TI - [Pharmacological studies of N-(2-mercapto-2-methylpropionyl)-L-cysteine (SA 96). VI. Effects on vitamin B6, metals and skin collagen in rats]. AB - N-(2-Mercapto-2-methylpropionyl)-L-cysteine (SA 96), an antirheumatic agent, and the main metabolite of SA 96, N-[2-methyl-2-(methylthio)propionyl]-L-cysteine (SA 679), were investigated for the effects on vitamin B6 (VB6), metals and skin collagen in rats in comparison with D-penicillamine (D-Pc). SA 96 had no effect on VB6 amount in serum and liver at doses of 30 mg/kg and 150 mg/kg, p.o., for 28 days, but SA 96 as well as SA 679 lowered the level in the liver slightly at a dose of 600 mg/kg. On the other hand, D-Pc lowered the VB6 level markedly both in serum and liver at doses of 150 mg/kg and 600 mg/kg, p.o., for 28 days. SA 96, SA 679 or D-Pc had no effect on urinary VB6 excretion. The degree of complexing of SA 96 as well as SA 679 with pyridoxal-5-phosphate in vitro was very slight as compared with D-Pc. SA 96 and D-Pc increased Cu and Zn excretion in urine, decreased Cu level both in serum and liver, and increased Zn level in serum. However, the degree of these effects of SA 96 on the metals was very slight as compared with D-Pc. SA 96 or SA 679 had no effect on skin collagen, neither soluble nor insoluble collagen, but D-Pc increased soluble collagen markedly. In addition, at a dose of 600 mg/kg, D-Pc decreased insoluble collagen.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4043868 TI - [Influences of free intake of nicotine on several circadian rhythms in rats]. AB - Male Wistar rats, aged 4 weeks, were kept in a temperature controlled room with a 12 hr light-dark cycle and given food and water ad libitum. The nicotine-treated group of rats was given water containing nicotine, which was estimated to be 10 mg/kg/day, for 40 days. Spontaneous motor activities, drinking activities and serum corticosterone levels showed circadian rhythms characteristic of a nocturnal animal in both the control and the nicotine-treated groups. As compared to the control group, however, the nicotine-treated group showed an increase in ambulatory activities, a decrease in drinking activities and a diminution of weight gain. In comparison with diurnal variations, serum corticosterone levels and liver nicotine oxidase activities increased in the nicotine-treated group during the dark period. However, the pattern of circadian rhythms characteristic of a nocturnal animal were not altered. PMID- 4043869 TI - [Effects of 4-(o-benzylphenoxy)-N-methylbutylamine hydrochloride (MCI-2016, bifemelane hydrochloride) on spontaneous motor activity under different experimental conditions]. AB - Effects of MCI-2016 on SMA changes were examined under several experimental conditions (normal conditions, hypoxia and head injury). Under normal conditions, MCI-2016 showed a significant increase of SMA after single administration of 12 mg/kg, i.p. Other doses (12.5-50 mg/kg, p.o. and 3-6 mg/kg, i.p.) of MCI-2016 were without significant effect. Under the same condition, MCI-2016 produced a dose-dependent increase of SMA after repeated doses of 12.5 to 50 mg/kg, p.o. (9 10 days administrations). After 5 days repeated administration, MCI-2016 significantly improved the decreased SMA due to hypoxia (rats) at 50 to 100 mg/kg, p.o. Furthermore, the drug also improved the decreased spontaneity due to head injury (mice) at 50 to 400 mg/kg, p.o. These improving effects of MCI-2016 were superior to those of Ca-hopantenate. The SMA increasing effect of MCI-2016 (12 mg/kg, i.p.) was antagonized more strongly by phenoxybenzamine than by haloperidol. In addition, the drug was shown to be rather antagonistic to the effects of anticholinergic agents. These effects may indicate the existence of qualitative differences between MCI-2016 and methamphetamine in the SMA increasing actions. It is also suggested that MCI-2016 may exhibit the above pharmacological effects through possible activation of noradrenergic and/or cholinergic mechanisms. PMID- 4043870 TI - [Pharmacological actions of iprazochrome on the vascular system]. AB - The pharmacological actions of iprazochrome (IC) on the vascular system were studied, and the following results were obtained: No death nor abnormal behaviors were observed in acute toxicity tests conducted on male and female mice and rats despite the administration of large doses of IC (10,000 mg/kg, p.o. and 80 mg/kg, i.v., respectively). IC inhibited dose-dependently platelet aggregation in vitro induced by arachidonate and ADP, whereas no effect was observed on ADP-induced respiratory depression in mice, which is closely related to platelet aggregation in vivo. The antiserotonergic actions of IC on the isolated external carotid arteries and femoral arteries in dogs observed in a noncompetitive manner were found to be 1/24 to 1/65 that of methysergide. On the other hand, IC showed no inhibitory effect on the paw edema of rats in vivo induced by serotonin. The inhibitory effect of IC on peritoneal dye leakage in mice was less than half that of phenylbutazone. IC prevented apoplexy in stroke-prone SHR (SHRSP) without lowering the blood pressure. Histological changes in the cerebrum of SHRSP were ischemic changes such as swelling of the neurons and shrinkage of the nuclei, mainly in the cerebral cortex and corpus striatum area. PMID- 4043871 TI - [Pharmacological effects of CM6912 and its main metabolites]. AB - Pharmacodynamic effects of ethyl 7-chloro-2,3-dihydro-5-(2-fluorophenyl)-2-oxo-1H 1,4- benzodiazepine-3-carboxylate (CM6912), a new benzodiazepine derivative, and its main metabolites (CM6913 = M1, CM7116 = M2) on the peripheral systems were investigated in several species of animals. In pentobarbital-anesthetized rabbits, CM6912 and M2 (1 or 5 mg/kg, i.v.) had little effect on blood pressure, heart rate and ECG, but it slightly reduced the respiration rate. M1 decreased the heart rate without affecting respiration, blood pressure and ECG. In conscious rabbits, CM6912 and M2 (1 mg/kg, i.v.) did not affect respiration, blood pressure, heart rate and ECG, but M1 (1 mg/kg, i.v.) increased the heart rate. CM6912 (5 or 30 mg/kg), when administered orally, also increased heart rate. In pentobarbital-anesthetized dogs, CM6912 and its metabolites (5 mg/kg, i.v.) decreased respiration and heart rate without affecting blood pressure and ECG. CM 6912 (5 mg/kg, i.v.) did not affect cardiovascular responses to the carotid occlusion, vagus stimulation, and pre- and post-ganglionic stimulation of cardiac ganglion in anesthetized dogs. CM6912 and its metabolites affected neither the spontaneous contraction nor the heart rate of isolated rabbit atria. These compounds also had no action on isolated aortic strips from rabbits. CM6912 and its metabolites did not affect the muscle tone of isolated guinea pig intestine, and it had no effects on the contractile responses to acetylcholine, histamine, serotonin and barium chloride. In isolated rabbit intestine, CM6912 and M2 slightly reduced the amplitude of contraction, while M1 had no effect. CM6912 and its metabolites did not affect the spontaneous motility of isolated non-pregnant and pregnant rat uteri as well as in situ non-pregnant rat uterus and isolated guinea pig vas deferens, including the contractile response to adrenaline. CM6912 and M2 relaxed isolated guinea pig trachea strips only at high concentrations. CM6912 and its metabolites did not affect the contractile responses of isolated rat diaphragm to electrical stimulation of the phrenic nerve. CM6912 (2 or 10 mg/kg, p.o.) did not affect the rat renal and hepatic functions. CM6912 influenced neither blood coagulation in rabbits nor blood hemolysis in rats. CM6912 and its metabolites did not affect the pupil size and its light reflex, and they did not produce a local anesthesia and edema. The present results suggest that CM6912 and its main metabolites exert only slight effects on the peripheral systems in animals. PMID- 4043872 TI - Hematologic values of normal Bolivian squirrel monkeys (Saimiri sciureus): a comparison between wild-caught and laboratory-bred male animals. AB - Complete and differential blood counts were conducted on 23 male squirrel monkeys (Saimiri sciureus) of Bolivian origin. The sample included 9 laboratory-bred and 14 wild-caught adult monkeys weighing between 600 and 1,500 g. The means of total white blood cell (WBC) counts, total hemoglobin and hematocrits of laboratory bred animals were found to be significantly different from those of wild-caught monkeys (p less than 0.01). Other hematologic parameters showed no significant differences between the two experimental groups. 3 of 14 (21.0%) wild-caught animals each had 1 reactive lymphocyte and 7% of the same group had 10 nucleated erythrocytes per 100 WBC. No reactive lymphocytes or nucleated erythrocytes were observed in laboratory-bred animals. The importance of these baseline data and the basis for the differences observed between laboratory and wild-caught monkeys are discussed within the context of experimental studies involving primates in which hematologic parameters are valuable. PMID- 4043873 TI - Cytogenetic study of complex hybrids in the genus Lemur (Primates Prosimians). AB - A cytogenetic study was carried out of several Lemur hybrids and their progeny. The effects of Robertsonian translocations in the heterozygous state on fertility and the possibility of a preferential transmission of metacentric trivalents are debated. PMID- 4043874 TI - [Demography and reproduction of Macaca sylvanus in different habitats in Algeria]. AB - Usually described as a cedar forest monkey, the Barbary macaque in effect has colonized a great variety of habitat types. At the moment, it is not known to what extent these different habitats are suitable for the species' survival. We tried to answer this question by comparing the demography of three monkey troops: one lives in a deciduous oak forest; the second lives in an nondeciduous cedar green oak forest while the third is found on rocky ridges of mountains without any arborescent vegetation. In the three sites, there is a true seasonal breeding season with most births taking place in April to May and most matings occurring in November to December. Details are given on reproduction parameters (sexual activity of females; fertility rates; young survival...). Monkeys densities are higher in cedar forest than in deciduous forest. The smallest density is found on mountain ridges. Forest troops are more numerous, highly stable; their growth rate is better and the population is relatively young. The situation is slightly better still in the cedar forest than in the oak forest with a sex ratio more in favor of females and a better survival of the young. The troop of the mountain ridges is an unstable group ranging from 10 to 25 individuals; the population is aging, with a low birth rate and more male infants surviving compared with females. Demographic differences between sites are discussed according to climate, food availability and human influences (tree-clearing and overgrazing). Conclusions are drawn from this situation, for species conservation. PMID- 4043875 TI - Sexual dimorphism in the postcranial skeleton of New World primates. AB - This study examines sexual dimorphism in 24 dimensions of the postcranial skeleton of four platyrrhine species: Callithrix jacchus, Saguinus nigricollis, Saimiri sciureus, and Cebus albifrons. The two callitrichid species show a relatively small amount of variation in the degree of sexual dimorphism among the different dimensions. Variation is considerably higher in the two cebid species as reflected by a mosaic pattern of sexual dimorphisms with males being significantly larger than females in some dimensions, and females significantly larger than males in others. In dimensions of the pectoral girdle and limb bones, males and females in each of the two cebid species are essentially scaled versions of each other, with males being peramorphic compared to females. This pattern is primarily the result of time hypermorphosis, i.e. an extension of the growth period in time in males. Rate hypermorphosis, i.e. an increase in the rate of growth in time in males, appears to play an additional role, however, in S. sciureus. By contrast, in dimensions of the true pelvis, sex differences in shape are dissociated from those in size. They are interpreted as the result of acceleration, i.e. increase in rate of shape change in females, as an adaptation to obstetrical functions. Interspecific analyses indicate positive allometry of mean degree of postcranial dimorphism with respect to body size. This coincides with previous findings by Leutenegger and Cheverud [1982, 1985] on the scaling of sexual dimorphism in body weight and canine size, and thus supports their model which posits selection on body size as the prime mover for the evolution of sexual dimorphism. PMID- 4043876 TI - Kondous laventicus, a new ceboid primate from the Miocene of the La Venta, Colombia, South America. AB - A new genus and species of fossil primate, Kondous laventicus, part of the Miocene La Venta primate fauna of Colombia, South America, is described here for the first time. Screening at a new quarry within the Monkey Unit of the Honda Formation, the Kyoto Site, has revealed dental remains of this new form of a large-sized ceboid. The La Ventan vertebrate fauna is comparable to the Friasian Land Mammal Age, indicating a middle Miocene age. Biostratigraphic studies suggest a 13.6-15.2 Ma for the Friasian faunal zone. Kondous is most closely allied to extant spider monkeys, Ateles, providing the first fossil evidence of their phylogeny. It also implies a nearly three-fold discrepancy between the molecular and paleontological estimates of the age of the Ateles lineage. PMID- 4043877 TI - Chronic toxicity/carcinogenicity study of FD & C Blue No. 2 in mice. AB - Charles River CD-1 mice were fed FD & C Blue No. 2 in the diet levels of 0.5, 1.5 and 5.0% in a long-term toxicity/carcinogenicity study. Each group consisted of 60 males and 60 females. Two concurrent control groups each of 60 males and 60 females received the basal diet. Maximum exposure was 23 months. No consistent compound-related or statistically significant biologically adverse effects were noted. PMID- 4043879 TI - Irreversible in vivo binding of thiabendazole to macromolecules in pregnant mice and its relation to teratogenicity. AB - The binding of [14C]thiabendazole ([14C]TBZ) to macromolecules in the liver, foetus and other tissues was investigated in Jcl:ICR mice on day 13 of gestation. TBZ suspended in olive oil was given orally in a dose of 1 g/kg body weight (5 microCi/mouse) and the mice (in groups of three) were killed 0.5, 1, 3, 6, 24 and 96 hr later. The bound radioactivity in the liver and foetus was at a maximum between 3 and 24 hr after treatment. The rate of decrease of the bound radioactivity was slower than that of total radioactivity. Bound radioactivity was also present in other tissues (including kidney, lung, heart, placenta and spleen). The level of bound radioactivity was measured in the liver and foetuses after oral administration of teratogenic doses of 200-1600 mg/kg. Disproportionate increases in bound radioactivity were observed in both tissues after administration of the highest dose. PMID- 4043878 TI - Induction of early lesions in the forestomach of rats by 3-tert-butyl-4 hydroxyanisole (BHA). AB - BHA was administered to Wistar rats at a dose level of 2% in a powdered diet for periods of 1, 2 and 4 wk. After 1 wk epithelial damage, mild hyperplasia and hyperkeratosis of the forestomach mucosa was observed. The hyperplasia and hyperkeratosis showed progression at wk 2 and 4 whereas other epithelial defects regressed. The lesions were most pronounced in the vicinity of the limiting ridge. A further 4 wk of feeding without BHA resulted in a complete regression of epithelial defects, although the hyperplastic changes were still apparent. Other rats were given 1 g BHA/kg body weight/day by gastric intubation in arachis oil for 1, 2, 4, 8, 16 or 32 days. Increased mitotic activity was observed after 1 day and mild hyperplasia after the second intubation, but inflammatory response and superficial defects were not prominent and the hyperplasia of the squamous epithelium did not appear to result from initial damage and subsequent hyper regenerative activity. A gradual regression of the hyperplastic changes occurred after eight daily intubations. The lesions were found in the apex of the forestomach remote from the limiting ridge. It is concluded that BHA incorporated in powdered diet or given in arachis oil by oral intubation causes lesions in the rat forestomach similar to that reported for BHA given in a pelleted diet (Ito et al. J. natn. Cancer Inst. 1983, 70, 343; idem, Gann 1983, 74, 459). The hyperplastic changes in the mucosa occur rapidly and their localization is dependent on the mode of application. Following withdrawal of the BHA there was almost complete regression of the lesion, only a residual mild hyperplasia remaining after 4 wk. PMID- 4043880 TI - Instant and brewed coffees in the in vitro human lymphocyte mutagenicity test. AB - Incubation of instant and 'home brew' coffees (caffeinated and decaffeinated) and of coffee aroma with cultured human lymphocytes in the presence and absence of S 9 increased the number of total aberrations. However, the increase was smaller in the presence of S-9 than in its absence. Pure caffeine tested with or without S-9 at doses equivalent to levels in caffeine-containing coffee did not give statistically significant increases of any type of aberration when compared with controls. In all in vitro test systems used to date, coffee and coffee aroma or their reactive compounds were metabolically deactivated in the presence of S-9. This could explain the negative results obtained in mutagenicity assays in vivo. PMID- 4043881 TI - Teratological evaluation of picloram potassium salt in rabbits. AB - The embryotoxic and teratogenic potential of orally administered picloram potassium salt was evaluated in New Zealand white rabbits. Artificially inseminated rabbits were given 0, 40, 200 or 400 mg picloram acid equivalent/kg body weight/day in the form of picloram potassium salt in aqueous solution on days 6 to 18 of gestation. The foetuses were removed for examination on day 29 of gestation. Transient weight loss was observed among rabbits given 200 or 400 mg/kg/day of the test material, though the total weight gain of the treated groups during gestation was comparable to that of controls. A few isolated, sporadic cases of foetal malformations were observed in the dosed groups, but there was no indication of a dose-related embryotoxic or teratogenic response to treatment. PMID- 4043882 TI - Long-term toxicity of hexachlorobenzene in the rat and the effect of dietary vitamin A. AB - The toxicological effects of analytical-grade hexachlorobenzene (HCB) were examined in two chronic studies. Study I was an in utero exposure carcinogenicity feeding experiment in which Sprague-Dawley rats, in groups of 40 males and 40 females except where noted, were fed from weaning on diets containing 0.0 (64 M/64 F), 0.32, 1.6, 8.0 or 40.0 (66 M/66 F) ppm HCB. After 3 months on test, the F0 rats were bred and 50 pups (F1) of each sex were randomly selected from every group. From weaning, when the F0 animals were killed, the F1 animals were fed their parents' diet for the rest of their life (130 wk). There were no treatment related effects on growth, feed consumption, haematological parameters or survival in either generation. Increased heart and liver weights were found in the 8.0 and 40 ppm F0 males. HCB had no effect on fertility but pup viability was significantly reduced in the 40 ppm group. Histopathological changes in the F1 generation included significant linear trends in the incidence of parathyroid adenomas and phaeochromocytomas in both sexes, neoplastic liver nodules in females, centrilobular basophilic chromogenesis of the liver in both sexes, peliosis of the liver in females, peribiliary lymphocytosis of the liver in males and chronic nephrosis of the kidney in males. In Study II, the toxicological effects of HCB were examined as a consequence of varying the dietary levels of vitamin A. In this single generation lifetime (119 wk) feeding study, groups of 50 weanling Sprague-Dawley male rats were randomly assigned to each of the following dietary groups: control, control + 40 ppm HCB, 1/10 the vitamin A content of the control diet, 1/10 vitamin A + 40 ppm HCB, 10 times the vitamin A content of the control diet and 10 times vitamin A + 40 ppm HCB. After 25 and 49 wk on test, five animals from each group were killed and subjected to haematological and histological examinations. All other aspects of evaluation were similar to those for the F1 generation in Study I. No consistent differences were observed in the haematological parameters and there were no significant differences in the incidence of pathological lesions between the test groups. The animals in the 1/10 vitamin A groups, with or without HCB, had significantly lower body weights and poorer survival than did their corresponding control (normal vitamin A) groups. PMID- 4043883 TI - Toxicity and neuropharmacology of cyclopiazonic acid. AB - Cyclopiazonic acid (CPA) was found to have many pharmacological properties in common with the antipsychotic drugs chlorpromazine and reserpine. Thus, in mice CPA at ip doses of 5-14 mg/kg body weight produced hypokinesia, hypothermia, catalepsy, ptosis, sedation without loss of righting reflex, tremor, gait disturbance, dyspnoea, opisthotonus, atypical convulsion and prolonged barbiturate-induced sleep. The ip LD50 of CPA was found to be 13 +/- 0.05 mg/kg. The tremors induced by near-lethal doses of CPA were associated with voluntary or forced movements (action tremors); they worsened during the days following treatment, but they were weak compared with the exhausting and continuous tremors of the whole body caused by 20 mg tremorine/kg (used for comparison). When death occurred only 24-259 min after administration of CPA (11-14 mg/kg), it was preceded by dypsnoea, cyanosis, opisthotonus and clonic leg movements and tonic extension of hind legs (convulsions). When death was delayed (2-6 days after CPA administration), it was preceded by prostration, ptosis, hypothermia, tremor and cessation of food and water intake resulting in cachexia; convulsions were not seen in this group of mice. CPA did not affect the rate of convulsion or death caused by either maximal electroshock or metrazol administration but it did delay the onset of metrazol-induced seizures. In rabbits, 10 mg CPA/kg body weight initially produced tachycardia, tachypnoea and sedation with an activated electroencephalogram. Of three rabbits given 10 mg CPA/kg one died, and in this rabbit slow delta waves were seen just before and during a brief period with clonic leg movements. In this animal death was accompanied by tonic extension of the hind legs, respiratory arrest and cardiac fibrillation; and epileptiform EEG was not seen at any time. The unexpected EEG activation with sedation in rabbits treated with CPA was similar to the effect of reserpine on EEG. PMID- 4043884 TI - Isolation and characterization of products from the nitrosation of the alkaloid gramine. AB - The nitrosation of gramine, a tertiary amine alkaloid present in barley malt, was carried out by reaction with sodium nitrite in buffered acetic acid (pH 3.4) for 1 hr at room temperature. Two major non-volatile products of the nitrosation reaction were isolated by preparative HPLC and characterized as indole-3 carboxylic acid and N1-nitroso-3-nitromethylindole. This interpretation was supported by spectral data. The nature of these products indicated that gramine did not undergo nitrosation by the expected mechanism of nitrosative dealkylation. A mechanism is offered to explain the labile nature of the dimethylamino group found in gramine. PMID- 4043885 TI - Susceptibilities of drugs to nitrosation under simulated gastric conditions. AB - Drugs of differing structures and pharmacological actions have been incubated at 37 degrees C and pH 2.0 under conditions simulating those within the normal fasting stomach. The nitrite concentration (25 microM) was kept as constant as possible for 3 hr in an attempt to mimic its in vivo replenishment from the saliva. The extents of N-nitrosation varied widely, but were less than those observed by Gillatt et al. (Fd Chem. Toxic. 1984, 22, 269) using the WHO Nitrosation Assay Procedure, in which the initial nitrite concentration is 40 mM, 1600 times greater, and the pH (3.0) is close to the optimum for the N nitrosation of secondary amines. The highest yield of N-nitroso compound was obtained with the benzathine salt of penicillin G whereas some drugs, including hydrochlorothiazide and chlorthalidone, produced no detectable N-nitroso derivative. The degree of N-nitrosation was consistently reduced when the initial nitrite concentration of 25 microM was not replenished during the incubations, underlining the importance of simulating the continuous supply of nitrite from the saliva. In all instances, the reactions of the drugs with nitrous acid were inhibited and, in most cases, completely prevented by the presence of ascorbic acid (125 mg). PMID- 4043886 TI - The consumption ratio of flavouring materials: a mechanism for setting priorities for safety evaluation. AB - The toxicological testing of the millions of known chemicals or even the thousands of food components is not practical at present. Therefore, priorities for testing should be set carefully, to ensure that primary attention is given to materials for which risk management can potentially improve public health. Most flavouring materials used today by the food industry occur widely in natural and traditional foods. A proposed Consumption Ratio (CR) relates the amount of a flavouring material found in natural and traditional foods to the amount added to food by food processors. A CR above 1 means that the consumption of the flavouring material takes place predominantly via traditional food. High CR values should establish that the priority ranking for testing these flavouring substances needs to be no higher than that for testing the complete foods. PMID- 4043887 TI - Monarticular nontraumatic synovitis of the metatarsophalangeal joint: a new diagnosis? AB - Seven patients presented with forefoot pain in the metatarsal head region, with an average age of 57 years, and no history of trauma. Six had pain in the second metatarsophalangeal joint, while one patient had pain in the third. Physical examination demonstrated generalized thickening of the involved metatarsophalangeal joint along with warmth and tenderness to compression. Range of motion was decreased in flexion and two patients had a subluxed metatarsophalangeal joint. All patients demonstrated some instability of the joint with dorsoplantar stress. Palpation of the intermetatarsal space demonstrated some evidence of irritation of the common digital nerve. The toe demonstrated some thickening. Roentgenograms demonstrated some widening of the metatarsophalangeal joint in four of these patients. One patient responded to conservative treatment, and the remaining six patients underwent synovectomy. In three cases the common digital nerve was resected. Follow-up was 16 months, and four of the six patients operated on felt their symptoms were completely relieved, one patient felt that the symptoms were improved, and one patient believed her surgery was of no benefit. Synovial tissue in all cases revealed pathologic changes of chronic synovitis. The etiology of this synovitis is unknown. The excessive synovium resulted in the joint thickening, which probably accounts for the neuritic symptoms, the generalized thickening of the toe, and the instability of the joint. Because of the poor response to conservative treatment, perhaps earlier synovectomy is the treatment of choice for this entity. PMID- 4043888 TI - Three-dimensional imaging of the ankle joint from computerized tomography. AB - A computer system was developed to rapidly reconstruct three-dimensional (3D) images of bone from computerized tomography scans of the ankle joint. Solid models of the bones were produced from the 3D image data through the use of a computer numerically controlled milling machine. A cadaver ankle joint was scanned, and models of the distal tibia and fibula and dome of the talus were made and compared to the actual bone specimens. The measurements of the models were within 3 mm or less of the bones in all three planes (average, 1.2 mm or 5.5%). These 3D images and models of bone should allow better visualization of joint pathology and a system for preoperative planning on exact bone models to optimize the results of surgery. PMID- 4043890 TI - Treatment of symptomatic first metatarsal shortened by surgery. AB - There are several complications that can result from shortening of the first metatarsal in the treatment of bunion. Metatarsalgia and recurrent deformity can be quite disabling. The surgical technique described in this brief report provides improved support of the metatarsal heads in walking while decreasing pain and enables the patient to stand for longer periods of time. The procedure is reserved for salvage of those patients with severe pain and deformity and in whom other salvage procedures have failed. PMID- 4043889 TI - Arthroscopy of the ankle: technique and normal anatomy. AB - The authors present a modified technique of ankle arthroscopy and describe the intra-articular anatomy of the ankle joint as it relates to the establishment of arthroscopic portals. Cadaveric dissection was used to demonstrate the relationship of the tendons and neurovascular structures to the placement of the arthroscope. Diagnostic arthroscopy of the ankle can be systematic and reproducible when the surgeon is knowledgeable of the intra-articular and extra articular anatomy of the ankle and when attention is given to accurate placement of the arthroscopic portals and to consistent surgical technique. PMID- 4043891 TI - Calcaneal osteomyelitis following steroid injection: a case report. AB - A 71-year-old male presented with unremitting heel pain in the region of his calcaneal tuberosity. He had been previously treated with steroid injections for plantar fasciitis. Diagnostic workup revealed a calcaneal osteomyelitis which was treated with a partial calcanectomy. This case underlines the need to rule out this expected but previously unreported complication. PMID- 4043892 TI - Primary mycetoma infection of the distal tibia secondary to an occult foreign body. AB - Mycetoma infections of the extremities usually present with characteristic cutaneous manifestations of a locally invasive chronic infection. Primary mycetoma infection of bone can occur by direct inoculation of the fungus to a bony prominence from a penetrating injury. The clinical presentation, the surgical management, and the use of oral antifungal agents differentiate primary mycetoma of bone from chronic mycetoma infections. PMID- 4043893 TI - The risks and benefits of distal first metatarsal osteotomies. AB - From a total of 138 patients who initially underwent either Chevron or Mitchell distal metatarsal osteotomies, 50 were available with complete pre- and postoperative data for study. Chevron osteotomies were performed on 60 feet (41 patients) and Mitchell osteotomies on 12 (nine patients). The results indicate that both procedures provide good or excellent subjective and objective results in about 90% of cases. There was no statistically significant difference between the procedures as regards the results. Age did not influence the outcome. Complications included damage to the proper digital nerve of the great toe in 30% indicating either direct injury to the nerve with subsequent neuroma formation or indirect injury by nerve entrapment. Osteonecrosis of the first metatarsal head occurred following Chevron osteotomies in 12 feet (12 of 60 or 20%) and following a Mitchell in one (one of 12 or 8%). However, four of the 10 (40%) patients who had a Chevron osteotomy plus a lateral adductor release developed osteonecrosis. Osteonecrosis is described and classified into three stages: stage I, the precollapse condition; stage II, the collapsed condition; and stage III, the osteoarthritic condition. The major causes of failure were preexisting osteoarthritis, injury to the dorsal proper digital nerve, and osteonecrosis. Theoretically, most of these should be avoidable. Significant metatarsus primus varus and MTP osteoarthritis are contraindications to distal metatarsal osteotomies. A tourniquet should be routine and the nerve, visualized and protected. If a distal osteotomy is performed, a concomitant lateral adductor release is contraindicated and stripping of the distal soft tissues should be minimal. PMID- 4043894 TI - The diagnostic value of postmortem blood glucose determinations in cases of diabetes mellitus. AB - In 24 cases of death in diabetic coma the peripheral venous blood showed glucose levels exceeding 3.5 mg/ml (mean value 7.76 mg/ml). In a control material of deaths of other causes the blood glucose was usually low and often zero, and all values were well below the lower limit of the diabetic concentrations. The acetone contents of the diabetic blood varied widely and were of limited diagnostic value. We conclude that glucose concentrations above 3.5 mg/ml in the peripheral blood indicate that death occurred in diabetic coma. PMID- 4043895 TI - A fatal poisoning with LSD. AB - Radioimmunoassay, high-performance liquid chromatography and capillary gas chromatography-mass spectrometry were used to detect and measure LSD in the first reported case of fatal poisoning by LSD. The levels found in ante-mortem serum and plasma and in post-mortem blood, liver blood and stomach contents are given. PMID- 4043896 TI - Detection of mustard gas bis(2-chloroethyl)-sulfide in urine. AB - Extraction procedure and detection of bis(2-chloroethyl)sulfide from urine samples of two patients are described using gas chromatography-mass spectrometry. Concentrations are found in the low ppb-range. The result is discussed in connection with the reactivity of this substance and the corresponding metabolites. PMID- 4043897 TI - The importance of the lymphatic system. PMID- 4043898 TI - [Lipoprotein patterns in gout and hyperuricemia]. PMID- 4043899 TI - [Measurement of muscle oxygen pressure in healthy subjects and patients with arterial occlusive disease]. PMID- 4043900 TI - [Cost saving and relieving the physician. The American boom in computer-assisted ECG evaluation and assessment invades Europe]. PMID- 4043901 TI - [Significance of the time factor for CCT findings in fully reversible stroke]. PMID- 4043902 TI - [Progress and new emphasis in neurologic diagnosis and therapy. Modern technologies and their clinical effects]. PMID- 4043903 TI - [Vertigo--hemiplegia--cor pulmonale--shock. Clinico-pathologic conference]. PMID- 4043904 TI - [Cell nucleus DNA content of female preinvasive neoplasms. Cytophotometric and morphologic studies]. PMID- 4043905 TI - [Hay fever: peroral desensitization as an additional measure]. PMID- 4043906 TI - [The drug tool should not become blunt. On the problem of self medication from the viewpoint of the family physician]. PMID- 4043907 TI - [Contraception in the mentally handicapped]. PMID- 4043908 TI - [Partnership, sexuality and contraception in mentally handicapped humans]. PMID- 4043909 TI - [Endoscopic retrograde cholangiopancreatography (ERCP) in childhood]. PMID- 4043910 TI - [Preventive andrology]. PMID- 4043911 TI - [Adjunctive AV fistula in femoro-crural bypass]. PMID- 4043912 TI - [Excretory urography--current indications of the status of a conventional diagnostic method. Status of nonionic and ionic contrast media]. PMID- 4043913 TI - [Contribution of computer tomography of the brain to differential typology and differential therapy of ischemic cerebral infarct]. AB - In order to provide a pathogenetically oriented differentiation of brain infarctions on the basis of CT-morphological criteria, the CTs of 422 patients with visible brain infarctions were analysed. All of the supratentorial lesions were classified according to topographical features and were associated with the underlying cardio-vascular and other general diseases. This concept lead to a typology of brain infarctions which allowed for a differentiation of ischaemic lesions due to cerebral microangiopathy on the one hand (i.e. lacunar infarctions, subcortical arteriosclerotic encephalopathy), and lesions due to cerebral macroangiopathy on the other. The latter were hemodynamically induced terminal supply area infarctions and watershed infarctions or territorial infarctions due to thromboembolism. A third group of symmetrical subcortical lesions were associated with hypoxia. The frequencies of cerebral lesions within the whole cohort were as follows: 34% cerebral microangiopathy, 45% macroangiopathy, 1% generalised hypoxia, 10% miscellaneous lesions and 10% non classifiable infarctions. Stenosing lesions of the extracranial brain supplying arteries were found in 22% of the microangiopathy group but in 71% of the macroangiopathy group. Patients with territorial infarctions presented with embolising extracranial vascular lesions in 42% and with embolising heart disease in 21% of the cases. Local thrombosis of the intracranial large arteries was a rare event. Hypoxia occurred due to haemorrhagic shock, carbon monoxide poisoning, air embolism and strangulation. The following conclusions were drawn: In patients with cerebral microangiopathy any procedures aimed at the diagnosis and therapy of major vessel disease are not useful. Therapy should follow the principles of internal medicine. If haemodynamically induced infarctions are present, the clinician's primary task is to look for high grade extracranial vessel lesions. Recanalizing techniques (endarterectomy and ECIC-bypass) are the main therapeutical strategies. In territorial infarctions the embolising extracranial vessel lesions may be haemodynamically non-significant. An intra arterial source of emboli should be removed by the vascular surgeon. In younger patients, however, and in patients with normal Doppler findings and/or multiple territorial infarctions, a cardiac source of emboli is highly probable and its diagnosis should be pursued consistently. Bilateral symmetrical ganglionic infarctions are indicative of hypoxia and help to exlude other causes of the severe neurological disturbances associated with this condition.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 4043914 TI - [Prevention of cerebrovascular circulatory disorders]. AB - On reviewing the literature, the meaning of risk factors causing stroke as well as their therapy or elimination as an effective prevention of cerebro-vascular disease is pointed out. Hypertension increases the risk of apoplexy by the fourfold, with regard to the diastolic values of blood pressure by the fivefold up to the tenfold. Consistent therapy of hypertension decreases significantly the incidence of cerebral apoplectic attacks. Manifested diabetes mellitus and even reduced glucose tolerance raise the risk of stroke by the threefold, even though factors frequently associated with diabetes (hypertension, overweight, hyperlipoidaemia) are taken into consideration. Hyperlipidaemia, hypercholesteraemia, and hypertriglyceridaemia stipulate an increase of the incidence of stroke by the twofold to the threefold. Morbidity rate rises if these abnormalities coincide with further risk factors (hypertension, reduced glucose tolerance, smoking cigarettes, hypertrophy of left heart-ECG), up to the sixfold. Nicotine consumption alone increases the risk of cerebral apoplectic attacks in relation to age, by the threefold up to the fivefold. In combination with the use of hormonal contraceptive drugs, the risk of morbidity rate in women rises to the sevenfold. Overweight of more than 30% aggravates twice the risk of stroke. Heart diseases of different kind increase the risk of apoplectic attacks by the twofold; in combination with hypertension by the fivefold. The intake of oral contraceptive drugs causes an increase of cerebral thrombo-embolic attacks by the threefold up to the fivefold, where by a relation to the content of oestrogen and to the disturbances of haemorheology is proven.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4043915 TI - [Postpuncture headache]. AB - The present study recorded prospectively subjective complaints after lumbar puncture as diagnostic procedure (n = 59), spinal - (n = 41) and peridural anaesthesia (n = 45) over a time interval of 28 days. Posture dependent headaches were never observed following peridural anaesthesis. This result disproves the hypothesis of a purely psychogenic origin of postpunctional headache. The frequency of occurrence of the postpunctional syndrome was 39% after lumbar puncture, but only 4.9% after spinal anaesthesis. The observed difference is due to the fact that needles with a smaller diameter are applied in spinal anaesthesia. PMID- 4043916 TI - [Duration of the effect of acetylsalicylic acid on circulating platelet aggregates in cerebral infarct patients]. AB - The number of "circulating platelet aggregates" was examined in 33 patients who had suffered a cerebral infarct. Examination was done before onset of treatment with acetylsalicylic acid (ASA), 2 hours after ASA medication, and 12 hours after ASA medication, employing a modification of the platelet function measuring method according to the authors Wu and Hoak. The significant increase in the number of circulating platelet aggregates, compared with healthy persons, was found to be significantly reduced 2 and 12 hours after ASA medication. After 2 hours, we found in only 6% of the patients an increase in the number of circulating platelet aggregates above the mean value + triple (simple) standard deviation for n = 71 healthy controls. 12 hours after ASA administration 30% of the patients had again passed beyond the liberally defined standard level of the method. PMID- 4043917 TI - [Effects of impurities on enzyme induction and toxicity in rats treated with 2,3,7,8-tetrachlorodibenzofuran]. PMID- 4043918 TI - [Stimulating effect of squalene on fecal excretion of a high toxic 2,3,4,7,8 pentachlorodibenzofuran (PenCDF) in rats]. PMID- 4043919 TI - Digital angiocardiography and echocardiography: fundamentals and future aspects. AB - Digital techniques of image data acquisition, processing and analysis were developed relatively early in cardiology but their broad clinical application lags behind the use of similar methods in angiography, even though these techniques have shown their advantages in reducing contrast material and X-ray dose, in quantitative evaluation of circulatory parameters and in high quality real-time electronic image storage. Recent developments in the fields of angiocardiographic image acquisition, in image processing and in the design of advanced digital processors are reported. The possibilities for an integration of echocardiographic imagery (especially of echo contrast studies) into angiocardiographic image processing are discussed. Medical and technological research is needed to define still more precisely the medical needs and to improve the technical means for digital angiocardiography and echocardiography. PMID- 4043920 TI - Computerized geometric evaluation of angio- and echocardiographic images. AB - Since the first comprehensive computerized videometric systems for quantitative assessment of the dynamic morphology and function of the heart have been developed, angiocardiographic image generation and computer aided evaluation have improved considerably. As a second method for morphological imaging echocardiography is also established in cardiology, so that videometry branched off into angio- and echocardiometry. In this paper, the common aspects of both methods are discussed concerning manual outlining and computerized contour representation, additional storage of anatomical landmarks labelled by digits and letters, and list-directed automated evaluation of data. It allows standard graphical documentations including comparisons of global volumetric and functional results for individual patients as well as versatile research orientated evaluations of oblique semi-axes, sectorial areas, wall thicknesses, shape parameters, spatial orientation and derived global and regional functional parameters for patient groups. As an example wall thickness measured from echographic long and short axis views and from angiographic projections are compared. PMID- 4043921 TI - Clinical relevance of video-angiocardiometry in the pediatric age group. AB - Routine quantitative assessment of diagnostic angiocardiograms of children with congenital heart disease is only practiced by a few groups. General availability of high quality computer technology and software as well as the increasing surgical treatment of complex congenital heart diseases warrants a critical review of the potential of quantitative angiocardiography in the pediatric age group. Video techniques allow recording and evaluation of the respective anterior posterior and lateral projections side by side on one TV-field, obviating time consuming handling of conventional films with separately recorded projections. Reproducibility of this observer dependent technique is excellent. The statistical error of the clinically important normal values during the period of growth is in the range observed for other biological methods and allows separation of normal and overloaded ventricles. Angiocardiometric parameters quantitatively describing ventricular spatial orientation, shape, size, and function characterize overloaded left and right ventricles of simple congenital heart diseases. For the assessment of the severity, prognosis, and indication for an operation in an individual patient angiocardiometry in most cases adds only information which has to be evaluated in conjunction with that of clinical examinations and other laboratory techniques. Angiocardiometry is of particular value - also for the individual patient - in more complex congenital heart diseases for the monitoring of ventricular size and function before and after one or more-stage operations. Thus deficiencies of operative methods can be delineated and may lead to improvement and introduction of new ones. Application of contrast medium and X-ray saving digital subtraction methods, possibly in conjunction with semi-automated contour detecting techniques, will allow an even more detailed angiocardiometric evaluation with broader acceptance in pediatric cardiology. PMID- 4043922 TI - Health care innovation in an era of cost containment. PMID- 4043923 TI - The illusion of discounts in the health care market. PMID- 4043924 TI - Medical education indebtedness: does it affect physician specialty choice? PMID- 4043925 TI - Binding of steroid hormones and anabolic agents to bovine sex-hormone binding globulin. AB - Binding of some selected steroids and anabolic agents to bovine sex-hormone binding globulin (SHBG) was investigated. SHBG binding affinities, relative to the reference hormone 5 alpha-dihydrotestosterone, were estimated for the compounds. The results demonstrate that binding of steroid hormones to SHBG is facilitated by the 17 beta-hydroxyl group, possibly involving hydrogen binding, and by the methyl group at C-19 of the steroid moiety. Structural modifications at C-17 of a steroid molecule involving esterification, epimerization or reduction of the 17 beta-hydroxyl group, or introduction of a bulky 17 alpha group have the effect of decreasing the SHBG binding affinity of the steroid molecule. PMID- 4043926 TI - In vitro steroid secretion by intact bovine ovarian follicles in a superfusion system. AB - A superfusion system for single intact follicles is described. Bovine follicles were superfused for 5 to 10 hours. Progesterone and testosterone secretion was stable after an adaptation period of 150 min. A 5-minute stimulation with hCG resulted in a 2-fold increase in progesterone secretion. Superfusion for 450 minutes of 3 small follicles of similar size and in the same ovary next to each other showed different secretion patterns of progesterone and testosterone. Superfusion for 150 minutes of follicles obtained from 2 pairs of ovaries showed that follicular size is not a sufficient criterion to predict the progesterone and testosterone secretion pattern. Closeness of follicles (big or small) to a corpus luteum did not impair their ability to secrete progesterone and testosterone. It is concluded that a superfusion system as has been described in this report is an effective and desirable method to study the physiology and pathophysiology of single intact follicles. PMID- 4043927 TI - Intravenous glucose infusion fails to alter monocyte insulin-binding affinity in normal subjects. AB - Previous investigations have demonstrated an increase in monocyte insulin receptor affinity two and five hours following oral carbohydrate loading. The present studies were undertaken to see if intravenous (IV) glucose challenge provokes a similar increase in monocyte insulin binding affinity. 25 grams of glucose were given to 10 lean normals and monocytes were isolated for 125I insulin tracer binding studies (8.4 X 10(-10) M) at 0, 1 and 5 hours after glucose loading. The mean data show that monocytes develop a small, statistically insignificant increase in insulin-binding affinity one hour after intravenous glucose (mean +/- SEM, 7.28 +/- 1.06 ng/ml compared to basal 50% insulin displacement value, B50, of 9.25 +/- 1.62 ng/ml). B50 values demonstrated no increase in binding affinity at five hours (10.77 +/- 2.22 ng/ml). Prior studies have shown a 50 to 70% decrease in B50 following oral glucose, indicating a rapid increase in receptor binding affinity after carbohydrate ingestion. In contrast the present studies have shown that after IV glucose six normals had no decrease in B50 at one or five hours, while the remaining four normals had a 35% decrease at one hour but no decrease at five hours. Intravenous glucose loading, unlike an oral carbohydrate challenge, fails to provoke an acute, consistent increase in monocyte insulin binding affinity at these time points. Elevations in plasma glucose and insulin do not by themselves induce the acute increase in receptor affinity. PMID- 4043928 TI - Chlorpropamide alcohol flushing at high chlorpropamide dose is not specific for non-insulin dependent diabetes. PMID- 4043929 TI - Effects of five days verapamil administration on serum GH and PRL levels. PMID- 4043930 TI - Reduced norepinephrine turnover in interscapular brown adipose tissue of Japanese KK mice. PMID- 4043932 TI - Pathology of seven mucous cell adenomas of the bronchial glands with particular reference to ultrastructure. AB - The pathology, including ultrastructure, of seven mucous cell adenomas of the bronchial glands is described. They occurred as polypoid intraluminal lesions in both male and female patients between the ages of 7 and 55 years (mean 26 years). Histologically they were all benign and consisted of predominantly mucus secreting cells arranged in acini or ducts or in solid groups. A little squamous differentiation was evident in four cases, insufficient in our opinion, to justify the term mucoepidermoid tumour. By electron microscopy, many tumour cells resembled mucous cells of the bronchial glands, containing typical large mucous granules of finely granular, reticular or fibrillated material, and sometimes small electron-dense bodies. In four cases some cells showed both secretory granules and features of squamous differentiation such as numerous tonofilaments and desmosomes. Oncocytic differentiation was seen occasionally. PMID- 4043931 TI - An immunopathologic evaluation of lymph nodes from monkey and man with acquired immune deficiency syndrome and related conditions. AB - Morphology and immunostaining of lymph nodes taken from rhesus monkeys and man are compared. The monkeys were inoculated with biologic materials known to transmit simian acquired immune deficiency syndrome (SAIDS) and the human biopsies were obtained from homosexual men with persistent generalized lymphadenopathy syndrome or acquired immune deficiency syndrome (AIDS). The lymph nodes from monkey and man share common immunohistochemical features, ranging from exhuberant follicular hyperplasia to lymphocyte depletion stage. The follicular hyperplasia differed from reactive controls by the larger follicular size and disorganization within the follicular centers as well as an increase in the number of cells with the T suppressor/cytotoxic phenotype. The lymphocyte depletion stage showed a loss of reactive follicles and small T lymphocytes with a predominance of mature monocytes/macrophages. Most monkeys and humans with the lymphocyte depletion morphology fulfilled the case definitions for AIDS and SAIDS while those with follicular hyperplasia usually had 'prodromal' findings. The simian agent is associated with alterations in lymph node morphology and immunostaining which parallel the changes seen in spontaneous human cases supporting a similar pathogenesis for AIDS and SAIDS. PMID- 4043933 TI - Expression of MHC Class II antigens by oesophageal epithelium in herpes simplex oesophagitis. AB - An immunoperoxidase technique with monoclonal antibodies for the identification of lymphocyte subsets and MHC Class II antigens was applied to oesophageal biopsies from two patients with herpetic oesophagitis. Oesophageal epithelial cells were found to express the MHC Class II antigen. The inflammatory infiltrate of the lamina propria was composed of both B lymphocytes and T lymphocytes. PMID- 4043934 TI - Non-conventional chondrosarcomas and chondrogenesis. AB - Pattern formation in chondroid development is compared with growth models exhibited by mesenchymal and myxoid chondrosarcomas. The results reveal strong similarities between mesenchymal chondrosarcoma and normal chondrogenesis. The fine vascularization of the tumor lobules of myxoid chondrosarcoma is discussed in relation to chondroid differentiation. A common histogenetic approach to the interpretation and classification of these neoplasias is proposed. PMID- 4043935 TI - Malignant epithelioid schwannoma of superficial soft tissue? A case report with immunohistology and electron microscopy. AB - Malignant epithelioid schwannoma is a well-defined entity. However epithelioid tumours arising other than in a nerve trunk, in a benign nerve sheath tumour or in neurofibromatosis are problematical. We describe a case of a nodular tumour of the cheek which recurred twice without metastasis. Light microscopy showed an amelanotic epithelioid tumour. Immunohistology showed positive staining for vimentin and S100 protein and electron microscopy showed distinctive appearances suggestive of schwannoma. We discuss the differential diagnosis of the tumour, compare it with reported tumours resembling both melanoma and schwannoma and conclude that this may be a further example of the distinctive tumour reported as "malignant epithelioid schwannoma of superficial soft tissues'. PMID- 4043936 TI - Ventures show cooperation with MDs up. PMID- 4043937 TI - Hidden costs of staff cuts: suits, lengthy compensation. PMID- 4043938 TI - Hospital goods and services to go up in '86: forecast. PMID- 4043939 TI - The future of the health care system. PMID- 4043940 TI - PPA contracting: a California experience. PMID- 4043941 TI - Affluent consumers most discriminating: survey. PMID- 4043942 TI - Executive salaries to rise 6.1 percent in '86. PMID- 4043943 TI - Hospital emergency departments learn how to make money. PMID- 4043944 TI - Administration opposes tax-policy, health-benefit link. PMID- 4043945 TI - National leaders meet to push indigent care higher on priority list. PMID- 4043946 TI - Uneven effects of wage-index changes divide industry. PMID- 4043947 TI - Industrial clinics represent prime targets for hospitals in setting diversification strategies, a new survey finds. PMID- 4043949 TI - Hospital conference center promotes health education. PMID- 4043948 TI - Outpatient sale of materials-management services boosts revenues, promotes services to physicians. PMID- 4043950 TI - Pathogenesis of "fibrosis" in interstitial pneumonia: an electron microscopic study. AB - Seven cases in which interstitial fibrosis developed in patients who had acute interstitial pneumonia were studied ultrastructurally to elucidate the pathogenesis of the interstitial thickening seen by light microscopy. Interstitial fibrosis is generally thought to result from fibroblast proliferation and collagen deposition, and this mechanism was confirmed. However, two additional mechanisms that also contributed to the interstitial thickening were identified. One, which was not described previously, involves folding of portions of alveolar septa or collapse of entire alveoli and permanent apposition of their walls. This process occurred in areas that had been denuded of alveolar lining epithelium. Granular pneumocytes attempting to re-epithelialize the denuded basal lamina proliferated over the surface of apposed septa, thereby combining the folded or collapsed alveoli and forming a single thickened septum. The second mechanism involves incorporation of intra-alveolar exudates into alveolar septa. It occurred when granular pneumocytes re-epithelialized along the luminal surface of intra-alveolar debris overlying denuded alveolar epithelial basal laminae. The relative importance of each of these mechanisms in the pathogenesis of interstitial fibrosis and their role in the more common chronic interstitial pneumonias are unknown. However, their recognition may inspire new approaches for the prevention and treatment of interstitial fibrosis. PMID- 4043951 TI - Follicular proctocolitis and neuromatous hyperplasia with lymphogranuloma venereum. AB - Lymphogranuloma venereum (LGV), a sexually transmitted disease, is caused by certain immunotypes of Chlamydia trachomatis. Proctitis due to LGV may be histologically indistinguishable from Crohn's disease of the rectum, thereby creating a diagnostic and therapeutic dilemma. The pathologic features found at autopsy at The Johns Hopkins Hospital in the 28 patients in whom LGV had been diagnosed clinically were reviewed, with the clinical features, to determine whether any of those features could be used to distinguish between LGV and Crohn's colitis. The results showed that although many of the pathologic findings in the intestines of subjects with LGV were similar to those observed in patients with Crohn's disease, the distribution of lesions in the colons of subjects with LGV was distinctly different from that observed in patients with Crohn's colitis. With LGV, the salient histopathologic lesions consisted of follicular lymphohistiocytic-plasma cell infiltrates in the submucosa, muscularis propria, and serosa; neuromatous hyperplasia in the submucosal and myenteric plexuses; and extensive thickening and fibrosis of the bowel wall. The rectum was uniformly involved by these processes and, in addition, had deep ulceration and fissuring, while more proximal segments of the colon were generally spared of severe chronic inflammation. Thus, the colonic lesions of LGV have a distal left-sided predominance, in contrast to the usual right-sided predominance with rectal sparing in Crohn's colitis. PMID- 4043952 TI - Pulmonary veno-occlusive disease: involvement of pulmonary arteries and review of the literature. AB - Pulmonary vessels from 26 patients with pulmonary veno-occlusive disease were studied histologically and morphometrically. In addition to the well-known obstruction of veins and venules, pulmonary arteries were also narrowed or obliterated in approximately half of the patients. It is unlikely that the arterial intimal fibrosis, which was sometimes as severe as the fibrosis in the veins, was secondary to the venous obstruction; rather, like the venous alterations, it probably resulted from organization of thrombi. It is possible that primary damage to the vascular wall elicited thrombosis. Such an injury may also have caused the arterialization of the venous walls, a common finding that cannot always be explained by distal narrowing of larger veins. Although the etiology of pulmonary veno-occlusive disease is obscure, it seems increasingly likely that multiple noxious agents may induce this condition. In children no predilection for either sex has been observed, but in adults, men are affected twice as often as women. PMID- 4043953 TI - The significance of mitotic rate: a retrospective study of 127 thyroid carcinomas. AB - The association between mitotic rate and biologic behavior was studied in 127 cases of thyroid cancer. Based on the observation of 12,700 high-power fields (HPF), the mitotic rate varied from 0 to 316 (33.3 +/- 4.9) mitoses/100 HPF. Mitotic rate differed among the four types of thyroid cancers and correlated inversely with the differentiation of the tumors, being highest (156.8 +/- 32.9) in the undifferentiated tumors and lowest (17.3 +/- 2.4) in the papillary tumors. By analysis of variance (AOVA), the relations between mitotic rate and the sex or age of the patient, maximal diameter of the tumor, and vascular or capsular invasion were assessed, but significant relations were not found (r2 = 44.2 per cent). Follow-up observation, possible in 74 patients, showed mitotic rate to be significantly related to the survival period (Student's t-test; P values ranging from 0.02 to 0.05). The patients who were alive five and ten years after surgery had had lower mitotic rates than those who had died during the same follow-up period. The correlation of low mitotic rate with a high degree of differentiation and low potential for invasion might, in part, explain the better surgical cure rates for papillary thyroid carcinoma than for other types of thyroid cancers. PMID- 4043955 TI - Coexisting juvenile polyps and tubulovillous adenoma of colon with carcinoma in situ: report of a case. AB - The coexistence of juvenile and adenomatous polyps is confirmed by the present case of a 17-year-old girl who had two juvenile polyps and a tubulovillous adenoma of the colon with carcinoma in situ, a clinically benign lesion. The relation between the juvenile and adenomatous processes and the risk of the development of colonic carcinoma in such cases remain ill defined. PMID- 4043954 TI - Non-Hodgkin's lymphoma classification: ultrastructural morphometric studies for the quantification of nuclear compartments in situ. AB - The condensed chromatin distribution in the nuclei of lymphocytes in non Hodgkin's lymphoma (NHL) is a key element, along with nuclear size and shape, in the classification of this disease for therapeutic and prognostic purposes. This report describes the ultrastructural comparative quantification of the condensed chromatin and the interchromatinic (nuclear matrix or euchromatin) region in the nuclei of mitogen-stimulated human peripheral T lymphocytes and mouse spleen B lymphocytes, human germinal center lymphocytes, and lymphocytes in ten cases of NHL of a variety of subtypes. The sequential morphologic nuclear changes induced in lymphocytes by mitogens are reflected in human germinal center lymphocyte populations. The common features include the changes in the distribution and volume of condensed chromatin aggregates, as well as the fact that the major increments in nuclear volume during lymphocyte transformation result from increases in the volume of the interchromatinic region. In all subtypes of NHL analyzed morphometrically, subpopulations of lymphocytes were identified in which mean nuclear, condensed chromatin, and interchromatinic volumes were more or less equivalent to those of normal lymphocyte subsets in germinal centers in reactive hyperplasia. However, in NHL the abnormal cytologic characteristics of the nucleus result, at least in part, from a complex interplay of condensed chromatin distribution and amount, and the size of the interchromatinic region. Further complexity is introduced by the fact that in NHL these two nuclear compartments can independently be normal, increased, or reduced in size. Morphometric quantification of lymphocytes in NHL indicates that the interchromatinic (matrix) region of the nucleus is the key element in establishing the nuclear volume of neoplastic lymphocytes. The structural and functional, ribonucleoprotein interchromatinic region of the nucleus was visualized in normal and neoplastic lymphocytes by regressive uranyl-EDTA staining. Quantitative morphometric analysis indicates that the cytologic appearance of neoplastic lymphocytes, even within subtypes of NHL, is heterogeneous and that condensed chromatin quantity and distribution may be more critical than nuclear size in distinguishing between certain subtypes of NHL. Improvements in the classification of NHL will occur only with understanding of the alterations in the biologic mechanisms controlling gross nuclear organization and the morphologic events of the various differentiation pathways available to antigen-stimulated lymphocytes. PMID- 4043956 TI - Congenital generalized fibromatosis causing spinal cord compression. AB - An unusual case of congenital generalized fibromatosis in which involvement of the spinal dura mater was accompanied by flaccid paralysis in the lower limbs is presented. PMID- 4043957 TI - Water-clear-cell hyperplasia mimicking parathyroid adenoma. AB - The case of a patient with primary hyperparathyroidism in whom water-clear-cell hyperplasia (WCCH) involved only the superior glands, and disproportionately so, is presented. In addition, unlike the cases of WCCH described previously, a rim of normal parathyroid tissue was observed at the periphery of each gland in this case. It is speculated that these findings are not necessarily peculiar, but may reflect an earlier stage of the disease. Such cases may mimic parathyroid adenoma, thereby leading to inadequate surgical therapy. PMID- 4043958 TI - Specificity of CEA and primary germ layers. PMID- 4043959 TI - Primary acquired melanosis. PMID- 4043960 TI - Vasculitis and connective tissue disease syndromes. PMID- 4043961 TI - Brown fat and adrenal pheochromocytoma: association or coincidence? PMID- 4043962 TI - A biochemical and immunological approach to the identification of H-Y antigenic proteins secreted from Daudi cells. AB - Conditioned culture medium from Daudi cells was used as a source of soluble H-Y antigen. Concentrated culture medium was labeled with 125I and then fractionated by gel filtration. Column fractions were assayed for the presence of H-Y antigen by urease-ELISA. H-Y antigen-containing fractions were then pooled and subjected to an improved immunoprecipitation protocol. Three predominant H-Y antigenic proteins were identified with estimated molecular weights of above 200,000, 50,000, and 20,000. PMID- 4043963 TI - A 45,X male with evidence of a translocation of Y euchromatin onto chromosome 15. AB - A 19-year-old male with azoospermia was found to have a 45,X karyotype with additional euchromatic material on 15p. The parents' karyotypes are normal. The cytogenetic data, the positive H-Y-typing, and the presence of Yp-specific restriction fragments detected in the proband's genome by molecular DNA probes suggest that the short arm of the Y chromosome, including part of the centromere, is translocated onto the nucleolus organizer region (NOR) of chromosome 15. PMID- 4043964 TI - N-Acetylneuraminic acid storage disease. AB - Increased amounts of free sialic acid were found in body fluids, leukocytes, cultured fibroblasts, and liver tissue of a four-year-old boy with mental retardation, ataxia, and clinical and radiologic findings of a mild mucopolysaccharidosis. A diagnosis of Salla disease was made though in contrast to earlier reports, recurrent upper respiratory infections and hepatosplenomegaly were present already in infancy, and skeletal abnormalities of dysostosis multiplex were found in early childhood. Free sialic acid in the urine was identified as N-acetylneuraminic acid by 1H-NMR spectroscopy. Sialidase activities were normal. Increased amounts of bound sialic acid were found in liver and cultured fibroblasts and were attributed to an intracellular inhibition of sialyloligosaccharide-degrading neuraminidase by excessive amounts of free neuraminic acid. The molecular basis of N-acetylneuraminic acid storage disease is unknown but may be related to a defective transport mechanism preventing neuraminic acid from leaving the lysosomal compartment. PMID- 4043965 TI - A craniosynostosis in a boy with a del(7)(p15.3p21.3): assignment by deletion mapping of the critical segment for craniosynostosis to the mid-portion of 7p21. AB - A tiny interstitial deletion of 7p was found in a 5-month-old boy with a craniosynostosis and many anomalies. His karyotype was 46,XY,del(7)(p15.3p21.3). Here we present not only further evidence of an association between craniosynostosis and 7p monosomy, but also deletion mapping to indicate that the critical segment for craniosynostosis lies in the mid-portion of 7p21, that is at 7p21.2 or the proximal part of 7p21.3. PMID- 4043966 TI - Mapping of human thyroglobulin gene on the long arm of chromosome 8 by in situ hybridization. AB - We report the structural organization of a segment of the human thyroglobulin gene, located 70kb from the 3' end of the gene, containing the exons 8 and 9 starting from the 3' end. Selected probes from this region have been used for the chromosomal mapping of the thyroglobulin gene by in situ hybridization techniques. Only one site in the human haploid karyotype is labeled with the genomic DNA probes. Twenty percent of the grains are localized on the long arm of chromosome 8, mostly in the subregion q-2-23 q-2-24 of the long arm of chromosome 8. The localization of the autoradiographic grains suggests a subregional assignment of the human thyroglobulin gene locus to 8q 2-23 or 8q 2-24. PMID- 4043967 TI - Rapid method for the diagnosis of partial adenine phosphoribosyltransferase deficiencies causing 2,8-dihydroxyadenine urolithiasis. AB - More than half of the Japanese patients with 2,8-dihydroxyadenine urolithiasis only partially lack adenine phosphoribosyltransferase (APRT), while all the Caucasian patients with the same disease completely lack the enzyme. APRT activities in healthy heterozygotes for the complete APRT deficiencies were at the same levels as the Japanese patients, and simple enzyme assay does not distinguish between these two conditions. We have previously shown, using viable T-cells, that the enzyme was non-functional in the cells from the Japanese patients although they contain considerable APRT activities in the cell extracts. In the present investigations, we devised a rapid method using erythrocytes for the diagnosis of partial APRT deficiencies accompanied by severe impairment in adenine metabolism causing 2,8-dihydroxyadenine lithiasis. Thus, erythrocytes from three different families with 2,8-dihydroxyadenine urolithiasis associated with partial APRT deficiencies incorporated only minimal amounts of radioactive adenine, while normal erythrocytes incorporated significant amounts. These data indicate that severe impairment in adenine metabolism is shown not only in viable T-cells but also in viable erythrocytes. The present procedures provide a rapid method suitable for routine clinical use for the diagnosis of partial APRT deficiencies causing 2,8-dihydroxyadenine lithiasis. PMID- 4043968 TI - Analysis of crossing-over in a family with translocation 9;10 involving a chromosome 9 with a pericentric inversion. AB - The presence of two markers on chromosome 9, both a balanced reciprocal translocation and an inversion, allows morphologic demonstration of recombination between the normal and rearranged homologues. In the family under discussion 50% of the progeny studied (two of four) received a translocated 9 without the inversion from a parent with a translocated and inverted 9, indicating crossing over between members of the chromosome 9 pair. Thus the morphology of the chromosomes allows a recombinant event which is normally invisible to be seen cytologically. Theoretically after crossing-over the balanced reciprocal translocation heterozygote results from adjacent-1 segregation and unbalanced derivative chromosome combinations from alternate segregation. Therefore it cannot be assumed that the balanced progeny necessarily result from alternate segregation and the unbalanced from adjacent-1. The prenatal diagnostic studies presented in this report also show that chromosome analysis of other family members is required when the recombination between homologues produces differences in chromosome morphology between parent and fetus. PMID- 4043969 TI - An unusual translocation 46,XX,t(14;17)(q33.2;p11.2) in a woman with recurrent spontaneous abortions. PMID- 4043970 TI - Further segregation analysis of the fragile X syndrome with special reference to transmitting males. PMID- 4043971 TI - Microbiological and serological study of non-gonococcal urethritis with special reference to Mycoplasma genitalium. AB - Twenty-two men with non-gonococcal urethritis (NGU), 19 with gonorrhoea, and 22 without urethritis were examined for various micro-organisms. Chlamydia trachomatis was isolated from the urethra of 45% of men with NGU, 21% of those with gonorrhoea, but from none without urethritis. Ureaplasma urealyticum but not Mycoplasma hominis was recovered from a larger proportion of men with NGU than from those in the other groups. M genitalium was isolated presumptively from 32% of men with NGU, 12% of those with gonorrhoea, from 10% of men without urethritis, and from 42% of the men with NGU from whom chlamydiae were not isolated. U urealyticum, M hominis, and M genitalium were sought also in the rectum of men in the three groups. The first two micro-organisms were confined almost exclusively to homosexual men, whereas M genitalium was apparently not restricted in this way and was found particularly in this site in men with NGU. The latter mycoplasma may be a resident primarily of the intestinal tract. A fourfold or greater rise in the titre of antibody to C trachomatis was detected in about 20% of the patients with NGU, but not in other men. A similar rise in the titre of antibody to M genitalium was seen in 29% of the patients with NGU and in 12% of those without urethritis. A concomitant antibody response to M pneumoniae, which is antigenically related to M genitalium, was seen in one patient only. The responses to M genitalium suggest infection by this mycoplasma and indicate the need for further serological studies. PMID- 4043972 TI - Cryotherapy in the management of cervical ectopy. AB - Sixty-five patients with benign ectopy of the uterine cervix were treated by cryosurgery in the departments of genitourinary medicine at St Luke's Hospital, Bradford, and the Airedale General Hospital, West Yorkshire, without analgesia or anaesthesia. A symptomatic cure rate of 98% was achieved. There were no serious complications. This treatment is considered to be appropriate in genitourinary clinics in the United Kingdom as these have routine screening procedures for various genital infections. PMID- 4043973 TI - Condylomata acuminata in children: report of four cases. AB - Four cases of condylomata acuminata in children (two boys, two girls) are reported. Three children had perianal warts and one vulvar warts. One of the four children had been sexually assaulted, but a history of sexual contact was absent in the other three. Surgical excision was undertaken in one case and the others responded well to the local application of 25% podophyllin in benzoin tincture compound. In the absence of sexual contact, a non-coital mode of transmission of infection could be a possibility. PMID- 4043974 TI - Colonisation of the urethra with Streptococcus pneumoniae: a case report. AB - A 25 year old man developed mild urethritis and urethral colonisation with Streptococcus pneumoniae five days after a single orogenital sexual contact. The diagnosis was suspected because of the appearance of Gram positive diplococci in the urethral exudate. The incidence of urethral infection with S pneumoniae is not known. Pneumococci are unlikely to grow on the routine selective media used to identify Neisseria gonorrhoeae. PMID- 4043975 TI - Knowledge and acceptance of sex education at Agbo-Oba, Ilorin, Kwara State, Nigeria. PMID- 4043976 TI - [The role of pediatric assistants in health education]. AB - France has a category of health workers called auxiliary paediatric nurse (APN) who takes care of children from zero to six years of age. APNs play a very important role in the child's development since they feed him, wash him, play with him and look after him while he sleeps. Most of the time, however, they are not aware of the important psychological role they play and consider themselves only responsible for good hygiene. The author suggests that APNs should be taught during their training to make a number of psychological observations relating to the child's development and emotional life. It is important that APNs be also trained as health educators, a task they have to perform every day. PMID- 4043977 TI - [Education for health in France. New data for an improved strategy]. AB - Until recently there was a dearth of reliable statistics in France which hampered the implementation of prevention programmes. To remedy this situation, the government created in 1981 monitoring regional stations and requested a regular report on the health of the nation. The first such report entitled Health in France has just been published. It contains data on morbidity and mortality which will enable public health administrators to develop new strategies for preventive actions and health education. PMID- 4043978 TI - Transferrin C subtypes and rheumatoid arthritis. AB - Transferrin C subtypes were studied in patients with rheumatoid arthritis (RA) and controls. A significant association was found between the C2 type and RA. This association concerned mainly male patients and patients with a family history of polyarthritis. The results were discussed in relation to previous studies of the role of oxygen free radicals in the pathogenesis of RA and to a recently proposed hypothesis that the TfC2 gene confers an increased risk for cellular damage by hydroxyl radicals. PMID- 4043979 TI - Genetic linkage analysis of the carpal tunnel syndrome. AB - Two generations of a family with autosomal dominant carpal tunnel syndrome were studied for genetic linkage to 20 informative polymorphic blood markers. No linkage was demonstrated between the syndrome and the markers tested; exclusion of close linkage (lod score less than -2.0) was found for MNSs, ACP, GALT, GPT, GLO, Hp, Gc, and Pi. PMID- 4043980 TI - A two-step test for the heterogeneity of Fst values at different loci. AB - Under genetic drift and in the absence of selection, the Fst values are expected to be equal at all loci, and heterogeneity among such values is considered as an evidence for different systematic pressures affecting the different genetic systems considered. A two-step test is here proposed. Fst values at various loci are classified into two nonarbitrary groups through the analysis of the association between pairs of genetic and environmental variables; the heterogeneity is then assessed by Wilcoxon's two-sample test. Estimation of the theoretical variance of Fst, which causes major shortcomings in the test proposed by Lewontin and Krakauer in 1973, is thus avoided. PMID- 4043981 TI - Within- and between-zygosity variance in oral traits among US and Punjabi twins. AB - Cross-cultural comparison of twin variances reveals widespread heterogeneity among zygosities for dental occlusal traits, implying various biases in calculation of genetic variance or heritability estimates. These estimates are fairly robust for dental size traits, however. Differences in pattern between Punjabi (Northwest Indian) and American twins highlight the environmental differences that affect heritability determinations. PMID- 4043982 TI - Comparison of two preliminary methods of quantitative linkage analysis. AB - Two methods of quantitative linkage analysis were evaluated as screening tests for the presence of major genes that influence the expression of a quantitative trait. Our analyses of computer-simulated pedigree data indicate that both methods can be very informative in providing evidence for major genes. PMID- 4043984 TI - Human chromosomal heteromorphisms in Delhi newborns. II. Analysis of C-band size heteromorphisms in chromosomes 1, 9 and 16. AB - Quantitative analysis of C-band size heteromorphisms in chromosomes 1,9 and 16 was carried out in 200 Delhi newborns (100 males and 100 females). The percent size heteromorphisms for chromosomes 1,9 and 16 showed nonsignificant differences between the sexes. Homozygous size level combinations showed higher incidence than the heterozygous combinations for all the three chromosome pairs studied in both sexes. Our results are compared with other reported studies and the possible role of these heteromorphisms in ethnic/racial variation and in developmental disturbances is discussed. PMID- 4043983 TI - Glutathione reductase deficiency in association with sickle cell and thalassaemia genes in Saudi populations. AB - Glutathione reductase (GR) deficiency is reported to occur with a variable frequency in some populations of the world. In this study, the populations of two regions of Saudi Arabia which have a high frequency of sickle cell, thalassaemia and glucose-6-phosphate dehydrogenase (G-6-PD) deficiency, were screened for GR deficiency. Studies were also carried out to investigate the frequency of GR deficiency with other genetic blood disorders. The frequencies of complete GR deficiency were 0.0065 and 0.006, while those of partial deficiency were 0.146 and 0.074 in Al-Hafouf and Khaiber, respectively. GR deficiency was encountered in combination with the sickle gene, the G-6-PD deficiency gene and the thalassaemia gene in both regions. Individuals with GR deficiency showed slightly reduced haematological parameters. In thalassaemic/GR-deficient subjects, mean cell volume and mean cell haemoglobin were low, while in sickle cell anaemia patients with GR deficiency the haematological parameters were higher than in sickle cell anaemia patients without GR deficiency. PMID- 4043985 TI - Distribution of transferrin C subtypes among the Bedouin and non-Bedouin populations of Jordan. AB - The distribution of transferrin C subtypes was studied in the population of Jordan. The sample comprised 121 Bedouins and 382 other Jordanians from Amman. The frequency of TfC2 was found to be 0.26 among the Bedouins and 0.23 among the non-Bedouin population. TfD was present in low frequency (0.005) among both the Bedouin and non-Bedouin populations. PMID- 4043986 TI - Gene frequencies of plasminogen in Switzerland. AB - Plasminogen (PLG) polymorphism was studied by agarose gel electrophoresis and immunofixation in 308 unrelated individuals from Switzerland. The gene frequencies observed were: PLG 1 = 0.69, PLG 2 = 0.28, and rare alleles = 0.03. PMID- 4043987 TI - Placental-soluble aconitase polymorphism in Japanese. AB - Polymorphism of soluble aconitase was investigated in 152 Japanese placentae. The allelic frequencies were ACONS1 = 0.951 and ACONS2 = 0.049. ACONS2 appears to be rather high among Orientals including Japanese, while ACONS4 seems to be characteristic for Negroids. PMID- 4043988 TI - Monoclonal antibody to a highly glycosylated protein reacts in fixed tissue with melanoma and other tumors. AB - A highly glycosylated protein with a molecular weight of 30,000 to 60,000 and a protein core of 20,000 daltons has been identified by antimelanoma monoclonal antibodies. The antigenicity of this melanoma-associated glycoprotein (MAG) was not destroyed in fixed paraffin-embedded melanoma tissue, and was present in malignant cells of cutaneous superficial spreading melanomas in skin (31/33) and in half of all metastatic melanomas examined (5/10). The antigen was not expressed by normal melanocytes. The strong reactivity of dysplastic nevi with the anti-MAG antibodies was comparable to that seen in radial growth phase melanoma. Antigen expression was much weaker in compound nevi where reactivity ranged from moderate in the junctional component and the upper dermis to absent at the base of the nevus. PMID- 4043989 TI - Inadequacy of traditional ELISA for screening hybridoma supernatants for murine monoclonal antibodies. AB - Hybridomas producing anti-creatine kinase (CK) and anti-lactate dehydrogenase (LDH) antibodies were screened by enzyme linked immunosorbant assay (ELISA) with antigen coated onto plastic wells. Out of seven antibodies positive for each isoenzyme of CK, four antibodies failed to bind to the radiolabeled antigen in solution phase radioimmunoassay (RIA) or native antigen in competitive ELISA. Moreover, out of nine antibodies shown reactive with LDH-1 and seven antibodies binding to LDH-5 by ELISA, not a single antibody bound to either radiolabeled or native antigen in solution. Our results along with other recent studies strongly suggest that antigen conformation on solid phase may frequently be different from in solution and that screening by ELISA in which antigen is attached to solid phase is often inappropriate for determining the presence of useful monoclonal antibodies. PMID- 4043990 TI - The in vitro activity of lectin I from mistletoe (ML I) and its isolated A and B chains on functions of macrophages and polymorphonuclear cells. AB - We investigated the effects of ML I and its isolated chains, A and B, in regard to selected functions of phagocytes (human granulocytes, paraffin-oil stimulated M phi from guinea pigs). On these cells, ML I has no cytotoxic effect between 10( 14) and 10(-8) (trypan blue exclusion and ethidium bromide exclusion). Over the same concentration range, ML I and B chain diminish the negative surface charge of M phi and agglutinate M phi at concentrations greater than or equal to 2 X 10( 8) M (ML I) and greater than or equal to 3 X 10(-7) M (B chain), respectively. The diminishing of the negative surface charge shows two peaks, indicating the existence of two types of receptors on the M phi surface with different affinities for sugar-binding sites. Moreover, the B chain shows a third peak at higher concentrations (3 X 10(-8) M) that could be inhibited by D-galactose (greater than or equal to 10(-4) M). In comparison, the A chain reduces the surface charge at concentrations over 3 X 10(-7) M, but D-galactose has no effect on this. By means of the agarose droplet test, the spontaneous migration of M phi is inhibited in the sequence ML I much greater than B chain greater than A chain. The phagocytic activity of human leukocytes tested with a radiometric phagocytosis technique reveals an increasing effect only for the B chain; ML I and the A chain have no effect. Perhaps the mechanism of the described activities of ML I and its B chain are comparable with the action of lymphokines activating M phi. PMID- 4043991 TI - Cell shape of polymorphonuclear leukocytes is influenced by opioids. AB - The effects of beta-endorphin(beta-End), an endogenous opioid, were tested in vitro on shape changes in polymorphonuclear leukocytes (PMNs). Cell shape changes indicate alterations of the functional status of the cells. Within 2 min, beta End but not the opioid alkaloid levorphanol or the antagonist, diprenorphine, induced a cell spreading. Subsequently, beta-End and levorphanol (10(-8) M), but not the dextrorotatory isomer, stimulated an elongation of the cells. Both effects of beta-End could be antagonized by diprenorphine in an equimolar concentration. Thus, the effects were stereo-specific and antagonizable. In this test system, the morphological changes evoked by beta-End were equal to the effects of FMLP, a chemotactic substance, used as a reference. Our findings indicate that endogenous opioids might play a role in modulating the initial phase of the PMNs' offensive behaviour, presumably cell adherence and motility. PMID- 4043992 TI - Polymorphism of the fourth complement component in the dog. AB - The polymorphism of the fourth complement component was studied in 118 unrelated dogs from different breeds and 73 unrelated beagles. In the mixed breed population, five different variants were observed with the following gene frequencies: C4*1 = 3.9%; C4*2 = 13.6%; C4*21 = 6.0%; C4*3 = 9.0% and C4*4 = 51.1%. In beagles, only four variants could be identified with gene frequencies of C4*2 = 24.2%; C4*21 = 1.4%; C4*3 = 20.6% and C4*4 = 46.3%. In both populations analyzed positive linkage disequilibria between certain DLA antigens and C4 variants were recognized. The biochemical analysis of the canine C4 revealed a double-banding pattern for the C4 alpha chain which gives preliminary evidence for two gene loci encoding for the fourth complement component in the dog. PMID- 4043994 TI - Differences in surface antigen expression of human fibroblasts cultured from bone marrow compared with those obtained from skin and embryo lung tissue. AB - We have described the optimal conditions for the culture of human fibroblast cells from whole bone marrow aspirates and have shown that these fibroblasts differ in surface markers from those obtained from the skin and embryo lung tissue. All three fibroblast types express HLA class 1 antigens, together with an antigen found on T cells, granulocytes, white matter of brain and breast epithelial cells, but none of them expressed HLA class 2 antigens. In addition, skin fibroblasts expressed an antigen found on common acute lymphoblastic leukaemia cells, while bone marrow fibroblasts expressed an antigen found on human natural killer cells. Hence, all three types of fibroblasts can be separated on the basis of their surface markers, thereby suggesting a difference in maturation pathways. PMID- 4043993 TI - Monoclonal antibodies which react with lymphocyte-lysed target cells and which cross-react with complement-lysed ghosts. AB - Monoclonal antibodies were raised against a human natural killing system and screened against targets lysed either by human lymphocytes in antibody-dependent cellular cytotoxicity (ADCC), or by human complement. Two monoclonals were identified which bound specifically to both types of killed targets. More detailed studies with one antibody showed that it inhibited ADCC, both as intact antibody and as the F(ab')2 fragment. Intact antibody enhanced natural (NK) killing, although the F(ab')2 fragment inhibited NK killing. The data support the hypothesis that lymphocyte-mediated killing involves a complex analogous in nature to the complement membrane attack complex. In addition, the antibodies provide evidence to suggest that this complex has antigenic determinants in common with the complement membrane attack complex, and indicate the possibility that the two systems are derived from a common ancestor. PMID- 4043995 TI - Immunological responses to monoassociated Bifidobacterium longum and their relation to prevention of bacterial invasion. AB - After monoassociation of Bifidobacterium longum with germ-free BALB/c mice (nu/+, heterozygous to nu gene), B. longum was recovered (10(2)-10(4) viable units per organ) from the mesenteric lymph nodes, liver and kidneys for 2 weeks post intragastric inoculation, but not after 4 weeks and later. Cessation of bacterial translocation was not observed in monoassociated nude (nu/nu) mice. Anti-B. longum IgA antibody was detected by ELISA using B. longum cell wall antigen in bile from Week 1 and in ileac wall extract from Week 8 post-association in both nu/+ and nu/nu mice. Total IgA levels in bile, ileac wall extract and caecal contents were also elevated in both mice after monoassociation. Cell-mediated immunity measured by the footpad test and macrophage migration inhibition test using B. longum protein fraction was detected in nu/+ mice in Week 4 and later, but not in nu/nu mice. Nu/nu mice reconstituted 4 weeks prior to monoassociation with lymphocytes from flora bearing nu/+ mice developed delayed footpad reactivity and bacterial translocation stopped after 4 weeks. Cell-mediated immunity rather than IgA antibody correlated well with the cessation of translocation. PMID- 4043996 TI - Prevention of oral tolerance induction to ovalbumin and enhanced antigen presentation during a graft-versus-host reaction in mice. AB - Systemic hyporesponsiveness after ingestion of a protein antigen (oral tolerance) depends on antigen processing by the gut and the actions of immunoregulatory T cells. We have examined the effects of a graft-versus-host reaction (GvHR) on oral tolerance, since both immune status and intestinal function are altered in GvHR. The GvHR was induced in unirradiated (CBA X BALB/c)F1 mice by intraperitoneal injection of CBA spleen cells. The tolerance of systemic humoral immunity and of delayed-type hypersensitivity normally found in mice fed 25 mg ovalbumin (OVA) was partially abrogated from 1 to 3 weeks after induction of the GvHR. In addition, mice with GvHR had a persistent enhancement of systemic immunity to OVA, and this was associated with an augmented ability of spleen cells to present OVA to primed T cells. The phagocytic activity of the reticuloendothelial system, as established by carbon clearance tests, was not altered by the GvHR. These findings suggest that enhanced antigen-presenting cell activity interferes with the induction of oral tolerance, and may be another pathogenetic mechanism of intestinal hypersensitivity disease. PMID- 4043998 TI - [Clinico-experimental studies on the use of hyaluronic acid in skin healing processes. Preliminary data]. PMID- 4043997 TI - Effect of specific IgG on IgE-induced systemic anaphylaxis in the rabbit. AB - Immunization of rabbits as neonates and periodically thereafter has been shown to induce the long-term preferential production of specific IgE antibodies. Specific IgG antibodies are not detected in the majority (greater than 70%) of rabbits when classical immunological detection techniques are used, including heterologous PCA in guinea-pig skin. Nevertheless, in this study we demonstrate that all rabbits neonatally immunized to the antigen horseradish peroxidase (HRP) do produce low levels of specific IgG antibody detectable by an ELISA technique. Serum levels of anti-HRP IgG were found to be log normally distributed, with a geometric mean for the heterologous PCA-negative sera of 31.6 X/divided by 2.69 micrograms/ml. Serum anti-HRP IgE levels (log2 homologous PCA titres) are bimodally distributed. Specific IgG and IgE levels in individual rabbits have a significant direct relationship. Six heterologous PCA-negative and seven heterologous PCA-positive rabbits were challenged intravenously with HRP. All of the respiratory and circulatory alterations typical of IgE anaphylaxis occurred in every challenged rabbit. Regression analysis of percentage changes in the physiological variables vs log specific IgE level indicated that none of the changes was either directly or inversely related to the specific IgG levels. Also the mean changes of the heterologous PCA-positive vs negative rabbits did not differ significantly. Thus, we could find no evidence for either a blocking or enhancing effect of the specific IgG antibodies (range 10-529 micrograms/ml serum) on the IgE-induced anaphylactic reaction. PMID- 4043999 TI - [Therapeutic activity of a hydrocortisone-carbamide (urea) combination in hyperkeratotic and/or desquamative dermatitis]. PMID- 4044000 TI - [The problem of compliance in physician-patient relations]. PMID- 4044001 TI - [Recent advances with regard to the etiology of cutaneous leishmaniasis]. PMID- 4044002 TI - [Clinical, histological and statistical study of primary skin melanomas (300) observed in the four-year period 1980-1983]. PMID- 4044003 TI - [Urticarial vasculitis]. PMID- 4044004 TI - [Natural cytotoxic activity of lymphocytes in children with atopic dermatitis]. PMID- 4044006 TI - [Lichen nitidus. Considerations on 2 clinical cases]. PMID- 4044005 TI - [A case of Waardenburg-Klein syndrome]. PMID- 4044007 TI - [Furuncular myiasis caused by Dermatobia hominis]. PMID- 4044009 TI - [Nickel: a ubiquitous hapten]. PMID- 4044008 TI - [The half and half nail phenomenon in uremic patients. Clinical and epidemiological study]. PMID- 4044010 TI - [Erythrocyte filtration in alopecia areata]. PMID- 4044011 TI - Decreased natural killer cell activity after prolonged administration of interferon in cancer patients. AB - Two patients with metastatic neoplastic disease received 2-3 X 10(6) IU alpha recombinant interferon (IFN) 3 times/wk, every other week, for 3-6 mth. The natural killer (NK) activity of their peripheral blood leukocytes, was followed during the course of the treatment. A significant decrease was observed in the NK activity, which returned to normal values at the end of IFN administration. The treatment did not modify the evolution of metastasis. PMID- 4044012 TI - Murine monoclonal antibodies which recognize adenosine deaminase from calf, mouse, rat and man. AB - Three monoclonal antibodies against calf adenosine deaminase were obtained from mice. All three strongly cross-react with the rat and human forms of adenosine deaminase, and two of them with the mouse enzyme. We show that these reagents can be useful for the preparation of adenosine deaminase-free cell culture media and consider their potential interest for the early immunofluorescence detection of T cell acute lymphoblastic leukemias. PMID- 4044013 TI - Cyclosporin-A binds lymphocyte surface receptors induced by activation. AB - Cyclosporin A (CyA) is a new immunosuppressive drug of very considerable and widespread interest not only for clinicians and transplant immunologists but also for cell biologists concerned with activation mechanisms, as it causes a selective blockade of lymphocyte proliferation. Clearly, the molecular biology of CyA action is of fundamental importance, and in attempting to understand this we have looked for a cell surface receptor. We used indirect staining with antibody (at 4 degrees C and in azide) to ensure that only those CyA molecules held at the cell surface would be seen. The drug molecules which partition into the cell membrane, due to the extreme lipophilicity of CyA, are not detected by extracellular antibody. This technique differs from other methods using a directly labelled drug, where it is not possible to discriminate between specific and non-specific binding. Using high sensitivity flow cytometric analysis we were unable to find CyA on resting lymphocytes, whereas lymphocytes activated by concanavalin A (Con A) or mixed lymphocyte reaction (MLR) showed a CyA-dependent increase in fluorescence. PMID- 4044014 TI - In vitro production of IgE in humans: kinetic studies and analysis of serum enhancing and inhibitory factors. AB - By using a sensitive and reliable method for the measurement of IgE produced in vitro by peripheral blood lymphomonocytes, the following observations may be made. Serum obtained from atopic donors shows a significant capacity to enhance the in vitro synthesis of IgE of PBL from atopic as well as of non-atopic donors. On the other hand, serum obtained from non-atopic donors demonstrates a clear-cut inhibitory effect on IgE synthesis of cells from both atopic and non-atopic individuals. The kinetics of the IgE production was studied. As early as 30 min after initiation of culture, PBL of atopic individuals showed the capacity to synthesize large amounts of IgE. The IgE synthesis continued, with variations from case to case, for 7 days. This capacity of the cells is completely inhibited following incubation of the PBL for a short period of time with a protein synthesis inhibitor, cycloheximide. This in vitro procedure represents a valuable tool for the study and identification of the enhancing and suppressor factors of IgE synthesis present in the serum. PMID- 4044015 TI - The alloimmunogenicity of heated blood and lymphoid cells. AB - Murine lymph node cells heated to 45 degrees C for 1 h or 56 degrees C for 15 min lost their ability to provoke a primary cytotoxic alloantibody response, though they were able to provoke a secondary response in animals primed with normal lymph node cells two months previously. The primary immunogenicity of whole blood and spleen cell preparations was destroyed by 56 degrees C but not by 45 degrees C treatment. Treatment of spleen cells with 45 degrees C heat, and ammonium chloride to remove red cells, destroyed their immunogenicity, whereas ammonium chloride treatment alone did not, suggesting that the red cells were the immunogenic component of heated spleen cells and, by implication, of blood. Further evidence for a difference in the immunogenicity of 45 degrees C heated blood and normal blood was provided by the finding that heated blood did not prime for a response to 45 degrees C lymph node cells given two months later. Preliminary investigations of the tolerogenicity of heated cells were unsuccessful, indicating, in view of the published data, that the precise protocol for tolerance induction is very critical. PMID- 4044016 TI - The formation of immune complexes in primiparous and multiparous human pregnancies. AB - Using a recently developed ELISA, antibodies were detected in maternal sera with reactivity directed against determinants present on the plasma membrane of the outer layer of the placenta, the syncytiotrophoblast. The anti-trophoblast antibodies were present in maternal sera in the form of "free" antibodies and "immune complex" antibodies. Examination of the sera throughout gestation and from successive pregnancies revealed that the generation of anti-trophoblast antibodies and the formation of immune complexes was predominantly a first pregnancy and early second pregnancy event, with very little activity detectable in later pregnancies. It is proposed that immune recognition occurs in a first pregnancy, which generates some form of immunosuppression that involves the activation of suppressor memory cells. PMID- 4044017 TI - Lysis of primitive teratocarcinoma cells by non-activated macrophages. AB - The capacity of non-activated murine thioglycollate-elicited macrophages and bone marrow-derived macrophages to lyse primitive F9 teratocarcinoma cells lacking H-2 antigens was investigated. Both populations of non-activated macrophages killed F9 cells efficiently whereas they were not cytolytic against murine fibrosarcoma targets. In vitro activation by lipopolysaccharide induced the macrophages to lyse fibrosarcoma cells but did not significantly increase the level of cytolysis against F9. These results are consistent with the hypothesis that the absence of H-2 expression on target cells may serve as a signal for macrophage "foreign" recognition and cytolysis. PMID- 4044019 TI - Establishment of hybridomas secreting monoclonal antibodies to Chlamydia psittaci. AB - Eleven stable anti-Chlamydia hybrid clones by fusions between X63-Ag8653 myelomas and immune splenocytes from Chlamydia psittaci immunized F1 (C57BL6 X BALB/c) mice have been established which react with the 12 reference Chlamydia strains (seven C. trachomatis and five C. psittaci. Ten of these monoclonal antibodies are directed against the genera-specific epitope (40,000 MW component) for which prolonged immunization seems to be responsible. PMID- 4044018 TI - Anti-complementary amines are immunological adjuvants in mice. AB - Complement (C) inactivation by ammonia, ethylenediamine and methylamine in mouse serum was studied in relation to a possible adjuvant effect of the substances in a cell-mediated immune response. The amines caused a dose-dependent depletion of both alternative pathway (AP) and overall C activity in vitro and showed also pronounced adjuvant effects in the delayed type hypersensitivity response of mice to SRBC. A significant correlation between momentary inhibition of AP activity and adjuvanticity was observed (r = 0.9995; P approximately 0.02), suggesting a causative relationship between these two phenomena. Both effects seem to be a direct function of the number of amino-groups per molecule. Since, on the other hand, lysosomotropic activity of amines is known to decrease with the number of amino-residues, our findings exclude an important role of direct phagocyte inhibition in the immuno-adjuvanticity of these compounds. A longer persistence and improved presentation of antigen as indirect result of local C-depletion could account for the immunological adjuvant effects of amines. PMID- 4044020 TI - Effect of melphalan administration on the activity of natural killer and natural cytotoxic spleen cells of normal and tumor-bearing mice. AB - The effect of melphalan (L-PAM; L-phenylalanine mustard) administration on natural killer (NK) and natural cytotoxic (NC) activities of spleen cells from normal noninoculated BALB/c mice and mice bearing large MOPC-315 plasmacytoma tumors was investigated. Injection of L-PAM (7.5 or 15.0 mg/kg) had no effect on NK and NC activities of spleen cells from normal mice whereas stimulation by PHA was markedly suppressed. NK activity was markedly suppressed in spleens of tumor bearing mice whereas NC activity was not affected. Therapy with L-PAM of tumor bearing mice led to transient recovery of NK activity which was possibly related to the effect of L-PAM on macrophage suppressive activity on NK cells. It is concluded that NK and NC cell activities and the response to PHA stimulation are selectively affected by L-PAM administration. PMID- 4044021 TI - Qb-1, a new class I polypeptide encoded by the Qa region of the mouse H-2 complex. PMID- 4044022 TI - Ly-30: a new mouse lymphocyte surface alloantigen defined by a monoclonal antibody. PMID- 4044023 TI - Inhibition of association vs. dissociation of high-avidity DNA/anti-DNA complexes:possible involvement of secondary hydrogen bonds. AB - Recent results on the conditions of ionic strength needed to prevent the association of dsDNA with high avidity human anti-dsDNA, were compared with the insufficiency of even the highest practicable ionic strengths to effect the dissociation of such antigen-antibody complexes, once formed (1). Further analysis of these results make us conclude that such high avidity dsDNA-anti dsDNA complexes, which in the initial stages of their formation are mainly of the Coulombic variety, subsequently evolve, at least in part, into hydrogen bonds. PMID- 4044024 TI - Treatment and follow-up of morbidity detected in medical camps in a village. PMID- 4044025 TI - Social and demographic factors influencing the acceptability of injectable method for contraception in comparison with copper 'T' I.U.D. PMID- 4044026 TI - Granules are necessary for death of neutrophils after phagocytosis of crystalline monosodium urate. AB - Crystalline monosodium urate (MSU) produces inflammation in vivo and kills phagocytes in vitro. A plausible hypothesis to account for crystal-induced cell death is that ingested crystals perforate the phagocytic vacuole into which lysosomes have degranulated: "lysis from within." However, it has also been contended that degranulation is not required for crystal-induced cell death. To resolve this controversy, we have prepared neutrophil-derived cytoplasts ("neutroplasts") which are devoid of most cellular organelles, including lysosomal granules. Both intact neutrophils and neutroplasts ingested MSU crystals, but inhibition of phagocytosis by cytochalasin B reduced crystal induced death of neutrophils (release of lactate dehydrogenase) from 42% to 16% without altering lysis of neutroplasts (27% with MSU alone and 26% with MSU and cytochalasin B). Moreover, addition of serum, which prevents direct interaction of crystals with the outer plasma membrane, reduced lysis of neutrophils, reducing cell death from 42% to 25%. After 60 min incubation, serum was totally ineffective in reducing neutrophil death but continued to reduce lysis of neutroplasts from 61% to 13%. Thus, the MSU lysed neutroplasts under conditions in which it ruptured membranes of nonphagocytic structures (erythrocytes, liposomes), i.e., in the absence of serum: "lysis from without." These data suggested that death of neutrophils after internalization of MSU requires a component that is lacking in neutroplasts. Granules (lysosomes) are the best candidates for this component, supporting the general validity of the "lysis from within" hypothesis. PMID- 4044027 TI - Human vascular smooth muscle cells and endothelial cells lack catalase activity and are susceptible to hydrogen peroxide. AB - 51Cr release as lytic and cell detachment as nonlytic injury were employed to estimate neutrophil-mediated injury of cultured human vascular smooth muscle cells and endothelial cells. The reagents hydrogen peroxide or hypoxanthine xanthine oxidase produced dose-dependent killing and nonlytic cell detachment, which were specifically inhibited by catalase but not by superoxide dismutase. The concentration of hydrogen peroxide or xanthine oxidase to induce cell detachment was less than lytic dose, suggesting that cell detachment was a much more sensitive assay of injury. Neutrophil-mediated cell lysis averaged 15% at most and was mostly dependent on hydrogen peroxide, while neutrophil-mediated cell detachment was nearly 100% and its dependency on hydrogen peroxide varied from 46% to 60%. These results suggest that vascular smooth muscle cells and endothelial cells in neutrophil-mediated events are destroyed by a hydrogen peroxide-dependent process, mainly via a nonlytic cell detachment mechanism. There was no striking difference of sensitivity to hydrogen peroxide between vascular smooth muscle cells and endothelial cells. Vascular smooth muscle cells and endothelial cells contained fairly high concentrations of superoxide dismutase, but not catalase, activity. The sensitivity of these cells to hydrogen peroxide but not to superoxide may arise from the fact that these cells lack intracellular catalase activity. The injury of vascular cells, which constitute important components of blood vessels, may lead to vascular injury and subsequent tissue damage. PMID- 4044028 TI - Cytolytic effect of polylysine on rabbit polymorphonuclear leukocytes. AB - The cationic polyamino acids polylysine and polyarginine cause a time and concentration dependent lysis of rabbit polymorphonuclear leukocytes. Lysis, measured as LDH release, is preceded by exocytosis, as can be deduced from a higher lysozyme release than LDH release, at short incubation time or with low concentrations of polylysine. The lytic effect of polylysine could be annihilated with the polyanion polyglutamic acid. Monomeric lysine or arginine, or low molecular-weight polylysine, were not lytic. This indicates that positive charges on a polymeric molecule of sufficient chain length play a predominant role in the interaction. Substances that promote exocytosis cause an increase of lysozyme release and a reduction of LDH release, whereas inhibitors of exocytosis cause the reverse: less lysozyme release and more LDH release. Negatively charged sialic groups on the plasma membrane are not important for the interaction, because their removal does not affect the lytic effect of polylysine on the cell. The possibility that the lipid part of the plasma membrane is the point of attack for the polycations is discussed. PMID- 4044029 TI - Sensitivity of Capnocytophaga species to bactericidal properties of human serum. AB - Capnocytophaga is a newly described genus of gram-negative bacteria which can cause serious oral and extraoral infections in the susceptible host. In the present study, sensitivity of Capnocytophaga spp. to the bactericidal properties of human serum was investigated. Laboratory strains representative of Capnocytophaga sputigena, C. ochracea, and C. gingivalis and seven oral isolates of Capnocytophaga spp. obtained in primary culture were determined to be sensitive to killing by pooled normal serum. In contrast, little or no killing of Capnocytophaga spp. was observed when these organisms were incubated in the presence of hypogammaglobulinemic serum despite evidence for alternative pathway activation. However, hypogammaglobulinemic serum could be reconstituted to bactericidal activity by the addition of the immunoglobulin M fraction of normal serum. Capnocytophaga spp. failed to activate the classical pathway in hypogammaglobulinemic serum, thus ruling out an antibody-independent mechanism of killing. In contrast, good correlation was observed between serum-mediated killing and antibody-dependent classical pathway consumption. These results indicate that complement in the presence of bactericidal antibody may be an important determinant of host resistance to intra- and extraoral infections caused by Capnocytophaga spp. PMID- 4044030 TI - An early effect of the S component of staphylococcal leukocidin on methylation of phospholipid in various leukocytes. AB - On incubation of rabbit polymorphonuclear leukocytes with the S component of staphylococcal leukocidin at 37 degrees C, the 3H-labeled methyl group of S adenosyl[methyl-3H]methionine was rapidly incorporated into phospholipid. Subsequently, the methylated phosphatidylcholine was degraded by activated phospholipase A2. Complete blockage of the methylation of phospholipid by a mixture of erythro-9-[2-hydroxy-3-nonyl]adenine, adenosine, and L-homocysteine thiolactone markedly inhibited the activation of phospholipase A2 by the S component. It also inhibited the binding of 125I-labeled F component to the cells, but not that of the labeled S component. These results suggest that methylation of phospholipid in the cell membranes by the S component results in activation of phospholipase A2, which induces the binding of the F component to the cells. PMID- 4044031 TI - Depressed chemiluminescence response by influenza virus is enhanced after conjugation of viral subunits to muramyl dipeptide. AB - The effect on respiratory burst of murine spleen cells after in vitro exposure to influenza virus, subunits, or subunits conjugated to muramyl dipeptide (MDP) was studied by luminol-dependent chemiluminescence (CL) in response to stimulation by zymosan. CL induced by infectious influenza A virus was depressed but could be elevated to normal levels when MDP was added together with a low, but not with a high, dose of the virus. Profound depression of CL was induced by high doses of influenza A/Brazil, A/Bangkok, and B/Singapore subunits. The same amounts of viral subunits conjugated to MDP restored or even enhanced the CL responses of spleen cells from BALB/c and C57BL/6 mice. Splenic cells from BALB/c mice generated higher levels of CL than did cells from C57BL/6 mice. PMID- 4044032 TI - Evolution of inflammatory response and cellular immune responses in a murine model of disseminated blastomycosis. AB - A reproducible model of disseminated blastomycosis was established in C57BL/6 mice by intravenous injection of 10(6) yeast-phase Blastomyces dermatiditis organisms. The infection progressed over 5 weeks to involve lungs, brains, superficial fascia, livers, and spleens of mice. By week 5, there was a greater number of organisms in lungs and brains than in livers and spleens. The tissue response in lungs, brains, and livers progressed from acute neutrophilic invasion before week 1 to pyogranuloma formation by week 5. Lymph nodes and spleens were remarkably spared. By week 5, infected mice became anergic to intradermal challenge with both specific Blastomyces antigen and a nonspecific antigen (sheep erythrocytes). At this time, the response to concanavalin A or phytohemagglutinin by splenocytes was markedly less than that of normal controls. Likewise, the plaque-forming cell response to sheep erythrocytes by splenocytes from infected mice was diminished. In coculture studies, splenocytes from 5-week-infected mice reduced the plaque-forming cell response by normal splenocytes. The development of this murine model should prove useful for elucidating the perturbations of immunoregulation associated with disseminated blastomycosis. PMID- 4044033 TI - Adenylate cyclase activity of a 68,000-molecular-weight protein isolated from the outer membrane of Bordetella bronchiseptica. AB - A method was developed which is suitable for the isolation of substantial quantities of outer membrane proteins of Bordetella species in a water-soluble form. The extracted material may then be further fractionated in the absence of detergents by ion-exchange chromatography and preparative flat-bed isoelectrofocusing. These procedures facilitated the isolation of one of the proteins, of molecular weight 68,000, for which the antibody titer correlated with the degree of protection against nasal changes induced in specific-pathogen free piglets by Bordetella bronchiseptica infection (P. Novotny, M. Kobisch, K. Cownley, A. P. Chubb, and J. A. Montaraz, Infect. Immun. 50:190-198). This protein, which banded between 7.0 and 7.6 pH in preparative isoelectrofocusing, may be further purified with a monoclonal immunosorbent. Immunopurified protein showed adenylate cyclase activity. The enzymatic activity was found to be unstable during processing; i.e., although the crude extract showed up to 150 nmol of cyclic AMP per mg/min, the immunopurified protein showed a maximum of only 200 nmol of cyclic AMP per mg/min. Two strains of B. bronchiseptica, isolated from herds of healthy pigs showing no signs of atrophic rhinitis, did not produce the 68,000-molecular-weight protein and were negative for adenylate cyclase. However, it is not known whether the 68,000-molecular-weight protein is a component of adenylate cyclase or whether it is an unrelated protein associated with this enzyme in some unknown way. Adenylate cyclase activity from culture supernatants of B. bronchiseptica, B. pertussis, and B. parapertussis can be absorbed equally to the same monoclonal immunosorbent. PMID- 4044035 TI - Bacterial adherence to human endothelial cells in vitro. AB - Differences in the ability of bacteria to adhere to normal valvular endothelium may account for the predominance of particular species as pathogens in acute endocarditis. An in vitro adherence assay was developed to simulate the host surface encountered in acute bacterial endocarditis by using confluent monolayers of human endothelial cells. Adherence of 32 gram-positive and -negative blood culture isolates to this surface was compared. All five Staphylococcus aureus strains tested were highly adherent to endothelial cells, as was one gram negative strain (Serratia marcescens). The remaining gram-positive and -negative isolates, including four viridans streptococci, were relatively nonadherent. Transmission electron microscopy demonstrated attachment of Staphylococcus aureus and invagination of the underlying endothelial cell membrane at 1 h followed by engulfment of large numbers of bacteria after 3 h. The intracellular bacteria appeared to be contained within vacuoles. Preferential attachment of some strains of bacteria, in particular Staphylococcus aureus, to human endothelial cells occurred in vitro, suggesting that adherence is an important determinant of bacterial pathogenicity in acute endocarditis. Active uptake of bacteria by endothelial cells may help account for the virulence of Staphylococcus aureus in endovascular infections and for the ability of this organism to establish multiple metastatic foci of infection. PMID- 4044034 TI - Correlation of serum opsonins with in vitro phagocytosis of Streptococcus pneumoniae. AB - C-reactive protein (CRP), an acute-phase reactant which binds to phosphocholine (PC) in the pneumococcal cell wall, and anti-PC antibodies are protective against experimental pneumococcal bacteremia in mice. To determine the relative opsonic capacities of CRP and anti-PC compared with those of antibodies against pneumococcal capsular polysaccharides (anti-PCP), we correlated in vitro opsonic activity for serotype 7F Streptococcus pneumoniae with concentrations of CRP, anti-PC, and anti-type 7F PCP in human sera from 10 normal subjects and 38 patients with sickle cell (SS) disease, a high-risk group for pneumococcal infection. Opsonic activity, measured by a radiolabeled bacterial uptake assay, correlated with anti-PCP levels but not with CRP or anti-PC in both the normal subjects and patients with SS disease. Addition of CRP to normal sera did not increase opsonic activity for serotypes 4 and 7F S. pneumoniae, although it did so for serotype 27, a nonpathogenic strain unique for having PC in its capsule. CRP and anti-PC were not effective opsonins when they bound to the pneumococcal cell wall rather than the capsule. The protective effects of CRP or anti-PC against these serotypes may be produced by means other than complement-dependent opsonization. PMID- 4044036 TI - Purification and vaccine potential of Klebsiella capsular polysaccharides. AB - Capsular polysaccharide (CPS) from 18 Klebsiella strains of different capsular types was isolated and characterized. Purified CPSs were composed primarily of carbohydrate with trace quantities of protein, nucleic acids, and lipopolysaccharide. All CPSs were of a high molecular weight, possessing a Kd of 0.01 to 0.11 as determined by gel filtration over Sepharose CL-4B. Low levels of lipopolysaccharide present in all preparations were responsible for the highly pyrogenic nature of one-half of the CPS preparations. Treatment of capsular material with dilute NaOH in 95% ethanol markedly reduced the pyrogenicity of all preparations and had a negligible effect on their molecular weight. The immunogenicity of the various native CPSs for mice varied considerably from serotype to serotype, but all evoked an anticapsular immunoglobulin G response. Five of 18 NaOH-treated polysaccharides were significantly (P less than 0.05) less immunogenic than their native counterparts. Human immunoglobulin G prepared from volunteers immunized with either native or NaOH-treated KP1-0 capsular polysaccharide was equally effective at preventing experimental fatal Klebsiella pneumoniae burn wound sepsis in mice. PMID- 4044037 TI - Monoclonal antibodies against surface antigens of Bacteroides gingivalis. AB - Monoclonal antibodies against the various surface antigens of Bacteroides gingivalis were obtained by the fusion of murine myeloma cells (SP2/0-Ag14) with spleen cells of BALB/c mice immunized with the whole cells. Two monoclonal antibodies reacted with lipopolysaccharide, and the other two reacted strongly with capsule antigen. One showed reactivity with the hemagglutinin of the cells. The five monoclonal antibodies reacted with sonicated antigen from all B. gingivalis strains tested. No cross-reactivity of the monoclonal antibodies with antigens from nine species of other black-pigmented Bacteroids strains was observed. An immunoblotting test involving the use of these monoclonal antibodies indicated that the epitope of B. gingivalis lipopolysaccharide was polysaccharide with a high molecular weight of 40,000 to 60,000. The immunoblotting test also demonstrated that the epitopes of capsule antigen and of hemagglutinin were 27,000- and 40,000-molecular-weight proteins, respectively. PMID- 4044038 TI - Changes in intestinal fluid and mucosal immune responses to cholera toxin in Giardia muris infection and binding of cholera toxin to Giardia muris trophozoites. AB - The effect of Giardia muris infection on the diarrheal response and gut mucosal antibody response to cholera toxin was examined in mice. The results obtained showed that the fluid accumulation in intestinal loops exposed to cholera toxin was increased in mice infected with a low number (5 X 10(4) ) of G. muris cysts compared with the response in noninfected mice. This effect was associated with a marked reduction in absorption of oral rehydration fluid from the intestine. In contrast, mice infected with a high dose (2 X 10(5) ) of cysts showed a marked decrease in fluid accumulation in response to the toxin. This decrease might be related to the finding that both G. muris and Giardia lamblia trophozoites can bind significant amounts of cholera toxin. Evidence is presented which suggests that the gut mucosal antibody response, mainly immunoglobulin A but also immunoglobulin G, to an immunization course with perorally administered cholera toxin was depressed in mice infected with G. muris. The reduction in antibody levels was particularly evident when the primary immunization was made very early after infection. The serum antitoxin antibodies to the oral immunization with cholera toxin were, however, not affected. Likewise, the delayed-type hypersensitivity response against sheep erythrocytes in animals primed subcutaneously with sheep erythrocytes was not modified during the course of G. muris infection. PMID- 4044039 TI - Phagocytosis of staphylococci by human polymorphonuclear leukocytes is enhanced in the presence of endothelial cells. AB - The role of various surfaces in the phagocytosis of Staphylococcus aureus by human polymorphonuclear leukocytes (PMN) was studied. Uptake of both opsonized and unopsonized staphylococci on the surface of a monolayer of human venous endothelial cells was compared with uptake on an inert plastic surface, with an assay that uses radiolabeled bacteria. Uptake of unopsonized S. aureus was threefold higher on the endothelial cell surface than on the plastic surface and was followed by efficient killing of the phagocytosed staphylococci. Uptake of unopsonized S. aureus on endothelial cells was not inhibited by treatment of the PMN with pronase or 2-deoxy-D-glucose and was only partially inhibited by cytochalasin B treatment of the PMN. The supporting effect of endothelial cells on the phagocytosis of unopsonized S. aureus was not due to opsonization of the bacteria by immunoglobulin or complement from the endothelial cell surface, nor to coating with fibronectin. PMID- 4044040 TI - Expression of the cloned toxic shock syndrome toxin 1 gene (tst) in vivo with a rabbit uterine model. AB - Toxic shock syndrome (TSS) toxin 1 (TSST1) is produced by strains of Staphylococcus aureus associated with TSS. Purified TSST1 induces in rabbits a shock-like illness with many features similar to TSS in humans. These symptoms were also induced by TSST1-producing bacteria in diffusion chambers implanted in the rabbit uterus. Naturally occurring TSST1+ strains and a TSST1- strain harboring a pE194-derived plasmid carrying the cloned TSST1 determinant tst gave the same symptoms. TSST1- strains and a TSST1- strain carrying a pE194-tst plasmid with a deletion of the tst gene had no effect in rabbits. The results with the plasmid-carrying TSST1+ and TSST1- strains, which were isogenic apart from tst, show that the toxin is responsible for the illness in rabbits and suggest that it is a major factor in the pathogenesis of TSS. PMID- 4044041 TI - Demonstration of cholera toxin-related factor in cultures of Aeromonas species by enzyme-linked immunosorbent assay. AB - The production of toxins by Aeromonas species was examined by the suckling mouse test, the hemolysin test, and the enzyme-linked immunosorbent assay with anticholera enterotoxin. A factor that was immunologically related to cholera enterotoxin was produced by 5 of 14 strains of Aeromonas hydrophila and 4 of 15 strains of Aeromonas sobria. Analysis by these assays and by a test for heat stability suggested that the factor differed from hemolysin and from toxin that was active in the suckling mouse test. PMID- 4044042 TI - Lack of correlation between known virulence properties of Aeromonas hydrophila and enteropathogenicity for humans. AB - Five strains of Aeromonas hydrophila were selected for use in volunteer challenge trials. All five strains produced cytotoxin, hemolysin enterotoxin, lysine decarboxylase, acetylmethylcarbinol, and DNase. Two strains hydrolyzed esculin. All strains produced purulent hemorrhagic fluid accumulation in rabbit ileal loops, but failed to induce keratoconjunctivitis in guinea pigs. None of the strains produced mannose-resistant hemagglutinins. In challenge studies, diarrhea was demonstrated in only 2 of 57 human volunteers with doses ranging from 10(4) to 10(10) CFU. One person experienced mild diarrhea with 10(9) CFU of strain 6Y. A second person developed moderate diarrhea with 10(7) CFU of strain 3647. At higher doses, no diarrhea was seen in any of the volunteers. The other three strains (B158, SSU, 3284) failed to cause diarrhea and were not recovered from stools of volunteers. Additional virulence properties of A. hydrophila need to be sought before enteropathogenicity for humans can be established. PMID- 4044043 TI - Combined plasmid and peptide analysis of clinical and environmental Legionella pneumophila strains associated with a small cluster of Legionnaires' disease cases. AB - Plasmid and peptide analysis was used to characterize Legionella pneumophila strains isolated in the study of a small cluster of cases in hospitalized patients. The isolates from the Denver Veterans' Administration Medical Center could be clearly separated into three groups. Two of the three clinical isolates were found to be plasmidless, as were five of 19 environmental isolates. The patient isolates had plasmid and peptide profiles which were identical to the showerhead isolates to which each patient was exposed. Thus, the data suggest that the patients acquired their disease strains from environmental sites in their particular hospital wing, and that each wing of the building had its own unique flora of Legionella strains. The results also confirm the usefulness of using both these techniques when tracing transmission patterns of nosocomial disease. PMID- 4044044 TI - How often does chronic liver disease follow acute hepatitis B in adults? AB - The risk of developing the chronic hepatitis B surface antigen (HBsAg) carrier state after primary acute hepatitis B virus infection was examined in a prospective study of adults with acute icteric (clinically apparent) viral hepatitis. Enzyme immunoassay for IgM antibody to hepatitis B core antigen (IgM anti-HBc) was positive in 176 (93.1%) and negative in 13 (6.9%) of 189 patients positive for HBsAg and negative for IgM antibody to hepatitis A virus. The former were considered to be acute hepatitis B infections and the latter chronic carriers superinfected with another virus or acute exacerbation of chronic infection. At six months, all surviving acute hepatitis B patients had cleared HBsAg. All surviving chronic carriers remained HBsAg-positive. In another prospective study, 18 adults with subclinical hepatitis B infection also cleared HBsAg within six months. These data suggest that in contrast to newborns and children, adult patients rarely develop chronic antigenemia after acute hepatitis B infection. The postulated risk should mainly be attributed to misdiagnosis of cases of superinfection of chronic carriers or acute exacerbation of chronic infection. PMID- 4044045 TI - Concentrations of mezlocillin in the serum, heart valves, muscle and subcutaneous tissue of patients undergoing open-heart surgery. AB - 4 g mezlocillin as a five-minute intravenous bolus were given preoperatively to 31 adult patients undergoing open-heart surgery. Mezlocillin serum levels declined from 42.8 mg/l at 1-2 h after injection to less than 1 mg/l at 6-8 h after application. Concentrations in muscle and subcutaneous tissue varied between 18 micrograms/g and less than 1 microgram/g. Mezlocillin levels in heart valves were higher than those in muscle and subcutaneous tissue, thus suggesting rapid diffusion of mezlocillin. PMID- 4044046 TI - Influence of fosfomycin and tobramycin on vancomycin-induced nephrotoxicity. AB - Since combinations of fosfomycin and vancomycin or tobramycin and vancomycin could be of advantage in the therapy of staphylococcal infections, we studied renal tolerance of both combinations. The experimental animal was the rat and the parameters of nephrotoxicity were cyturia and enzymuria. The experiments showed that fosfomycin at dosages of 50 and 250 mg/kg protected against nephrotoxicity caused by vancomycin (dose: 50 mg/kg), whereas the administration of both tobramycin (dose: 2.5 mg/kg) and vancomycin (dose: 50 mg/kg) resulted in an increase of cyturia and enzymuria. However, repeated dosing of vancomycin (single dose: 50 mg/kg) led to renal accumulation when combined with fosfomycin (single dose: 250 mg/kg); renal vancomycin concentrations were lower. This study suggests similarities in the renal handling of vancomycin and aminoglycosides and demonstrates the possibility of reducing drug-associated nephrotoxicity. PMID- 4044047 TI - Dessication resistance in thermotolerant Campylobacter species. PMID- 4044048 TI - Cerebellar atrophy after typhoid fever. PMID- 4044049 TI - Neutrophil and monocyte adherence in diabetes mellitus, alcoholic cirrhosis, uraemia and elderly patients. AB - The neutrophil and monocyte adherence were assessed in patients with diseases which predispose them to increased risk of infections. Neutrophil adherence was found to be markedly impaired in diabetes mellitus, alcoholic cirrhosis and uraemia. Monocyte adherence was also depressed in patients with diabetes mellitus and alcoholic cirrhosis, but not in patients with uraemia. Thus, the increased susceptibility of these categories of patients to infection can be explained in part by a defect in adherence. In contrast, neutrophil and monocyte adherence in elderly patients were comparable to that in healthy young adults, which confirms previous observations that the age-dependent decline in immunological function affects mainly the T and B cell systems. PMID- 4044050 TI - Detection of a thermostable brain antigen in the circulation of patients after cerebrovascular accident. AB - Enzyme immunoassay was developed with a thermostable antigen of human brain and its corresponding antiserum of rabbit origin. Inhibition of this assay proved to be a sensitive technique for detection of this antigen in the circulation. Using the inhibition test, we tested 170 serum samples originating from 42 patients with cerebrovascular accident (CVA), 166 sera from 166 patients with other neurological disorders, and 56 sera from 56 normal subjects. Fourteen patients with CVA were found to be "positive' and 28 "negative'. Positive results in inhibition tests were first noted within 1-2 days after CVA and they appeared to decline to negative values within 3-5 weeks after CVA. None of the sera from subjects without CVA were positive. PMID- 4044051 TI - Glycoprotein allergens in pollen of timothy. I. Investigation of carbohydrates extracted from pollen of timothy (Phleum pratense) and purification of a carbohydrate-containing allergen by affinity chromatography on concanavalin A sepharose. AB - On extraction of timothy pollen with aqueous buffer high molecular weight material (MW greater than 3,500) containing the sugars arabinose, fucose, xylose, mannose, galactose and glucose was rapidly released. When the allergen extract was subjected to crossed immunoaffinoelectrophoresis with lectins incorporated in the first- or second-dimension gel, some allergens were clearly retarded. A basic glycoprotein allergen, probably the one known as antigen 30, was bound to concanavalin A (Con A) and also to a lectin from Pisum sativum. This allergen was purified by a combination of Con A-Sepharose and CM-Sephadex chromatography, giving a product that contained the following sugars: arabinose (1.4%), fucose (traces), xylose (1.3%), mannose (2.0%), galactose (7.6%) and glucose (10.5%). The purified allergen appeared essentially homogeneous on isoelectric focusing and on gel permeation chromatography. The allergenic activity and acid phosphatase activity, which have been correlated by previous workers, were demonstrated to be entirely separable. PMID- 4044052 TI - Allergens in pollen from mugwort (Artemisia vulgaris L.). I. Partial characterization of allergen preparations from mugwort pollen with emphasis on the carbohydrate moiety. AB - The results obtained in these studies show that certain mugwort allergens are extracted after 5 min extraction time and that there is little difference whether phosphate-buffered saline or NH4HCO3 is used as extraction buffer. An extraction time of 1 h appears to be sufficient for a quantitative extraction of the main part of the allergens present. When the extracts are dialyzed, cathodic antigens/allergens are lost. Addition of thiourea leads to a reduction in the coloured matter of the extract, but not in a sufficient degree to recommend the compound to be included in the extraction procedures of allergens from mugwort pollen. A few allergens are heat-resistant, and as these fractions are richer in carbohydrate than equivalent fractions not being heat-treated, these allergens might be of glycoprotein nature. Structural features of the carbohydrate moiety are also described as well as the total amino acid composition of the protein moiety. PMID- 4044053 TI - Influence of reproductive history on age at diagnosis of breast cancer and prognosis. AB - The effect on age at breast cancer diagnosis of age at menarche, age at first baby, parity and age at menopause has been determined for 739 unselected patients diagnosed between 1975 and 1980 as having operable breast cancer. Age at diagnosis was significantly and positively associated with ages at menarche, first baby and menopause. The average number of children significantly declined with increasing age at diagnosis. This was largely due to a change in the proportion of patients who were nulliparous (15% in women aged 41-50 years compared to about 30% in those over 60 years). A group of 1,989 normal women whose reproductive history was also collected between 1975 and 1980 showed similar trends between age and age at menarche, age at first baby and parity as the patients. Thus it appears that these reproductive parameters do not alter the time of onset of breast cancer but could be explained by temporal changes in reproductive patterns. There was no significant correlation between age at menopause and age at diagnosis for patients whose age at menopause was no more than 54 years and age at diagnosis no less than 55 years, respectively. It is therefore unlikely that age at menopause affects age at diagnosis. Postmenopausal patients with 3 or more children had a significantly shorter disease-free interval and lower survival rate than those with less children. None of the other parameters was associated with prognosis. PMID- 4044054 TI - Hereditary malignant melanoma is not linked to the HLA complex on chromosome 6. AB - Detailed HLA typing was performed in 11 families with hereditary cutaneous malignant melanoma (CMM) and dysplastic nevi to determine if the melanoma susceptibility locus was genetically linked to the major histocompatibility complex. Previously published data from 19 other families were re-analyzed in the same manner. When data from all 30 families were pooled and CMM was defined as the disease trait, the hypothesis of linkage was rejected for all values of recombination (theta) less than 40%. Data on family members' status regarding dysplastic nevi (DN), a well-characterized precursor of hereditary CMM, were available for our 11 families and 7 previously-reported families. Linkage analysis between the combined CMM/DN trait and HLA provided strong evidence against this hypothesis. Significant heterogeneity was observed when various sub groups of families were compared; these data suggested that preferential reporting of positive linkage findings and misclassification of study subjects' CMM susceptibility status may have contributed to previous beliefs that the hereditary melanoma gene was linked to HLA. When our data are combined with previously-published information, we conclude that there is strong evidence against linkage of a CMM/DN gene with the major histocompatibility complex. PMID- 4044055 TI - Expression of cell surface glycoproteins in human melanoma cell lines with different tumorigenic properties. AB - Human malignant melanoma cell lines characterized by either a high or a low ability to grow subcutaneously in athymic nude mice have been examined for their cell-surface glycoproteins. Striking differences were demonstrated between these 2 groups. Cells from lines of low tumorigenicity (LT group) displayed twice as much Vibrio cholerae neuraminidase and galactose oxidase accessible glycoproteins as cells from lines of high tumorigenicity (HT group) and each group of cell lines could be characterized by specific glycoprotein profiles. LT and HT group cells displayed similar amounts of periodate accessible glycoproteins, but sialoglycoprotein profiles were characteristic for each group of cell lines. Furthermore, whereas 87% of the sialic acid released by V. cholerae neuraminidase came from cell surface glycoproteins in HT group cells, only 53-55% of the released sialic acid came from surface glycoproteins in LT group cells. These results suggest that human melanoma cell lines exhibiting different tumorigenicity in nude mice can also be characterized by differences in composition and organization within the plasma membranes of their cell-surface sialoglycoproteins. PMID- 4044056 TI - Partial purification and characterization of a vascular permeability factor secreted by a human colon adenocarcinoma cell line. AB - The established human colon adenocarcinoma cell line, HT-29, secretes a vascular permeability factor (VPF) in vitro. The factor has been purified from serum-free conditioned medium by acidification, cation-exchange, and reverse-phase and anion exchange high-performance liquid chromatography. The VPF is a non-glycosylated acidic protein of apparent molecular weight 45,000, and is at least 4 orders of magnitude more potent than histamine as an inducer of vascular permeability. Its biological activity is unaffected by soybean trypsin inhibitor or by inhibitors of histamine, kinins, prostaglandins, or acid proteases. The VPF induces vascular permeability within minutes, which suggests a direct effect on the endothelial cell. PMID- 4044057 TI - Phorbol myristate acetate (PMA) suppresses polarization and locomotion and alters F-actin content of Walker carcinosarcoma cells. AB - This study demonstrates a novel feature of PMA, its ability to suppress chemokinetic polarization and locomotion of tumor cells. Walker carcinosarcoma cells exhibit two distinct types of polarization and locomotion, i.e. spontaneous polarization characterized by ruffles at the front and stimulated polarization and locomotion in response to the microtubule-disassembling agents colchicine, vinblastine and nocodazole, which are characterized by blebbing at the front. The tumor promotor phorbol myristate acetate (PMA), but not phorbol, was found to suppress both types of polarization and random locomotion at concentrations between 10(-8) and 10(-6)M. The effect of 10(-6)M PMA was virtually complete within 5 min. Inhibition of locomotion was due to both a reduction in the speed of migrating cells and the proportion of migrating cells. Changes in shape and chemokinesis of Walker carcinosarcoma cells were associated with alterations in the relative amount and the topographical distribution of F-actin as determined by NBD-phallacidin binding. Suppression by PMA was associated with loss of the polar topographical distribution of F-actin visualized by NBD-phallacidin binding. In the presence of PMA, the relative amount of F-actin was higher than in unstimulated controls and lower in cells exposed to microtubule-disassembling agents. PMID- 4044058 TI - Lung colonization and metastasis by disseminated B16 melanoma cells: H-2 associated control at the level of the host and the tumor cell. AB - We have studied the experimental metastasis of H-2+ and H-2- melanoma sublines in H-2b/b and H-2a/b hosts by enumerating pulmonary colonies 20-50 days after i.v. inoculation of tumor cells. In H-2b/b hosts, the H-2+ "B16-S" cells gave rise to a moderate number of metastatic colonies (mean: 6.3 +/- 6). The "BL16-L" sublines that had lost the expression of MHC class-I antigens, according to FACS-analysis and quantitative absorption tests, gave no metastases under the same conditions. Pretreatment of the H-2+ met+ B16-S with interferons (beta or alpha + beta) increased their H-2 antigen expression and the number of metastatic colonies (mean: 25 +/- 16). Interferon pretreatment of B16-L cells partially restored their H-2b expression and induced them to form a small number of metastatic colonies. The reduction in pulmonary colonization by the H-2 negative B16-L cells could be attributed to their rapid elimination by natural killer cells, already observed within 24 hr of inoculation of radiolabelled cells. H-2- B16-L cells were more susceptible than H-2+ B16-S cells to in vitro lysis by poly I:C-treated splenocytes, and they acquired full metastatic abilities if the hosts were treated with anti-asialo GM-I serum. In H-2a/b heterozygous hosts, the H-2+ B16-S cells also failed to metastasize. Reduced pulmonary colonization was evident by 24 hr after injection in comparison with H-2b/b hosts, and could be reversed by anti-asialo GM-I treatment of the hosts. In vitro, H-2a/b splenocytes were more cytotoxic to the B16 cells than syngeneic effectors. The results are discussed in relation to a recent hypothesis on a surveillance mechanism for elimination of cells on the basis of their lack (or insufficient expression) of host MHC genes. PMID- 4044059 TI - A potential role for the extracellular matrix glycoprotein laminin in macrophage tumor-cell interactions. AB - Although cell surface molecules are thought to be involved in macrophage (MO) tumor-cell recognition, the nature of these molecules remains unknown. In this study we have shown that the glycoprotein laminin may facilitate macrophage-tumor cell binding. Macrophage binding to tumor cells was assessed by measuring the adherence of radiolabelled 3-MCA2 induced malignant fibrosarcoma cells to syngeneic peritoneal MOs. Addition of exogenous laminin promoted the binding of a weakly metastatic subline of these tumor cells by 31-68%. These weakly metastatic tumor cells express negligible endogenous cell-surface laminin but display specific cell-surface receptors for binding soluble laminin. Exogenous laminin promoted MO binding of these tumor cells whether it was present during the assay or whether the tumor cells were pretreated with the laminin. This increase in binding was blocked by anti-laminin antibody. In contrast, MO binding of a strongly metastatic variant of the same tumor was not enhanced by the addition of exogenous laminin. This highly malignant fibrosarcoma line already expressed endogenous cell-surface laminin. Since the MOs were found to specifically bind 125I-laminin, the interaction between laminin-bearing tumor cells and MOs may be mediated via a specific MO plasma membrane receptor. Thus, the expression of cell surface laminin and its receptors on both tumor cells and MOs may provide a mechanism for promoting MO-tumor-cell binding. PMID- 4044060 TI - The effects of single versus triple intravenous injections of B16 melanoma cells on the development of pulmonary tumors in mice. AB - During natural metastasis, cancer cells are released continuously into the bloodstream and arrested in target organs; the process is repetitive rather than a single event. In this communication, the effect of preceding on successive "pulses" of cancer cells is discussed in relation to the arrest, retention and tumor formation of B16 melanoma cells in the lungs of mice receiving 3 separate tail-vein injections at 2-hr intervals. When animals received the same total number of cells in either 1 or 3 injections, no significant differences were detected in the initial arrest and subsequent retention in the lungs. However, 15 days after injection, mice which had received 3 pulses of cancer cells were found to have fewer pulmonary tumors than those which had received a single pulse of cells. The results show that interactions between 2 successive waves of B16 melanoma cells and their host did not affect the initial arrest and "short-term" retention of a third wave of radiolabelled cells. However, the "longer-term" experiments on tumor formation show that preceding pulses of cancer cells resulted in the lungs becoming more hostile to a succeeding pulse than was the case in appropriate controls. The results indicate that the relative metastatic capacities of cancer cells arrested in microvascular beds during hematogenous metastasis could well be diminished by antecedent interactions of this type. PMID- 4044061 TI - Retention of semifloating electrode catheter. AB - A semifloating electrode was prophylactically inserted in an 84-year-old man because of the presence of bifascicular block and the suspicion of acute myocardial infarction. After 6 days it was decided to remove the electrode, but its extraction was not possible. This case demonstrates that retention of semifloating electrode, although a rare complication of temporary right ventricular pacing, is more than a theoretical hazard. PMID- 4044062 TI - Acute myocardial infarction secondary to polycythaemia in a case of cyanotic congenital heart disease. AB - A case of coronary thrombosis resulting from secondary polycythaemia due to severe cyanotic congenital heart disease in a young girl of 19 years of age is described. This resulted in a fatal myocardial infarction. There was no evidence of coronary atheroma. PMID- 4044063 TI - Debate concerning the nature of the internodal atrial myocardium. PMID- 4044064 TI - Effects of nifedipine on forearm vascular resistance and venous capacitance in normal subjects and in patients with congestive heart failure. AB - The effects of oral nifedipine on limb hemodynamics were studied in 7 normal subjects, 8 patients with congestive heart failure and 2 patients who underwent sympathectomy of unilateral limb. Forearm venous capacitance remained unchanged both in normal subjects and in patients with congestive heart failure. In normal subjects, systemic vascular resistance decreased without change in forearm vascular resistance. On the other hand, both systemic and forearm vascular resistance decreased simultaneously in patients with congestive heart failure. In 2 patients with normal left ventricular function undergoing sympathectomy, limb vascular resistance decreased in the denervated side and increased in the contralateral innervated side. These findings indicate that the effects of nifedipine on forearm vascular resistance are dependent upon the circulatory state of the patient at the time the drug is administered, while venous dynamics were not changed by nifedipine, and that the difference in the density of sympathetic innervation results in a reordering of territorial blood flow by modifying the vasodilatation due to the calcium antagonistic action of nifedipine. PMID- 4044065 TI - The relation between left ventricular asynchrony, relaxation, outward wall motion and filling characteristics during control period and pacing-induced myocardial ischaemia in coronary artery disease. AB - To assess the relation between left ventricular asynchrony, relaxation, outward wall motion and filling in patients with coronary artery disease and normal systolic function, pressure measurements and left ventricular angiography were performed at rest and after pacing. Asynchrony and outward wall motion were quantified by segmental area-time curves. At rest, there were no differences in asynchrony and time constant between 10 patients with coronary artery disease and 10 normal subjects, while the early-filling rate was less in patients with coronary artery disease than in normal subjects. Six coronary artery disease patients with isolated left anterior descending disease displayed anterior outward wall motion which was less than that of normal subjects. In 10 coronary artery disease patients with pacing-induced angina, asynchrony increased, time constant prolonged and the early-filling rate decreased. In 6 coronary artery disease patients with isolated left anterior descending disease, anterior outward wall motion decreased after pacing. Thus, impaired early diastolic filling at rest in patients with coronary artery disease and normal systolic function may result not from asynchrony nor impaired relaxation, but from reduced regional outward wall motion of the affected area supplied by diseased coronary artery during early diastole. However, during ischaemia temporal asynchrony and impaired relaxation possibly add to left ventricular filling impairment in patients with coronary artery disease. PMID- 4044066 TI - Quantification of myocardium at risk in unstable angina: comparison of patients with and without previous infarction. AB - We studied two subgroups of patients with unstable angina pectoris: 35 without (Group A) and 73 with (Group B) previous myocardial infarction. The severity of coronary artery disease was assessed by means of a previously described scoring system. This scoring system was used to calculate the proportion of left ventricular myocardium fed by significantly (greater than 75% luminal area reduction) stenosed coronary arteries (called percent myocardium threatened). To estimate the amount of myocardium lost by previous infarction we used a four point wall motion score for each of seven left ventricular wall segments: a value of 2 was given to normokinetic segments, 1 for hypokinetic segments, 0 for akinetic and -1 for dyskinetic segments. The deficit in wall motion score was used to estimate the amount of myocardium infarcted. This was then subtracted from the proportion of myocardium threatened to yield the proportion of myocardium still in jeopardy. We found a different extent and severity of coronary artery disease between the two subgroups. In the group without previous infarction, the numbers of patients with one-, two- and three-vessel disease were 15, 9, and 11, respectively (or 43, 26, and 31%). In those with a previous infarction, the respective numbers were 11, 23, and 39 (or 15, 31.5, and 53.5%). This difference is statistically significant (P less than 0.01). The mean number of stenotic arteries was 1.9 +/- 0.9 in the patients without previous infarction and 2.4 +/- 0.7 in those with an infarction (P less than 0.05). Using the above mentioned scoring system the score was 3.2 +/- 1.4 in patients without previous infarction and 4.0 +/- 1.6 in those with previous infarction (P less than 0.05). The percent myocardium threatened was 53.6 +/- 24.1 vs. 68.7 +/- 24.7 (P less than 0.01). Wall motion score was 13.8 +/- 0.6 in Group A and 10.6 +/- 3.1 in Group B (P less than 0.01), which gives values for the proportion of myocardium infarcted of 1.6 +/- 4.2 and 24.2 +/- 22.0%, respectively. The percentage still in jeopardy (after subtracting that infarcted from that threatened) was 51.8 +/- 22.7 in those without and 44.2 +/- 31.1 in those with a previous infarction: this difference is not statistically significant. We conclude that patients with unstable angina pectoris who have sustained a previous myocardial infarction have more severe coronary artery disease than similar patients without previous infarction. The amount of left ventricular myocardium still in jeopardy of becoming infarcted is, however, the same. PMID- 4044067 TI - Meteorological influences on myocardial infarction in the metropolitan area of Milan. AB - We attempted to relate admission rate for acute myocardial infarction with some meteorological variables in a region having a temperate climate. We used 2830 consecutive episodes collected over a 2-year (1979-1980) period. The temperatures, atmospheric pressure, relative humidity, front passage, rain and snow and foehn wind have been associated in the past with acute myocardial infarction. No significant association with any of them was found in our study, nor any correlation over the time between admission rates in six different Coronary Care Units (at the time the only ones active in the area) which participated in the study. PMID- 4044068 TI - Influence of the chosen model of stenosis on pressure-flow relationships in isolated perfused arteries. AB - Passive changes in luminal diameter caused by a fall in the intravascular distending pressure at the site of a severe coronary artery stenosis were recently proposed as a possible cause of transient myocardial ischaemia. We tested this hypothesis in 5 dog carotid arteries perfused with blood at a constant inflow (100 mm Hg) and variable outflow pressures (40-0 mm Hg). Similar degrees of stenosis were induced either with an external circumferential snare or with an intravascular fluid-filled balloon catheter. In 39 experiments outflow pressure was progressively decreased from 40 to 0 mm Hg. This was done first in the absence of stenosis, secondly with an external stenosis (snare) and finally with an internal stenosis of comparable severity (fluid-filled balloon). When stenosis was absent or intraluminal, flow increased progressively from 109.1 +/- 39 to 136 +/- 55 ml/min (P less than 0.06) and from 23 +/- 16 to 34.2 +/- 16 ml/min (P less than 0.001), respectively. Resistance also rose because flow increased proportionally less than the pressure gradient. Conversely, when stenosis was produced by a snare, flow decreased progressively, from 23.9 +/- 17 to 10.7 +/- 15 ml/min (P less than 0.001). Assuming the reduction of flow was caused by the external stenosis compressing the wall into the lumen (against the intravascular pressure) we prepared an artificial vessel with a foam rubber wall inside a silastic tubing. In this artificial vessel (but not in a glass model) a snare stenosis caused reduction in flow when outflow pressure was lowered. Passive changes in caliber due to a reduced distending pressure do not therefore appear to be a cause of flow reduction. PMID- 4044069 TI - Combined cardiac cinefluoroscopy, exercise testing and ambulatory ST-segment monitoring in the diagnosis of coronary artery disease; a report of 104 symptomatic patients. AB - To enhance diagnostic accuracy in coronary artery disease, cardiac cinefluoroscopy for the detection of coronary artery calcification was combined with exercise test and ambulatory ST-segment monitoring in 104 symptomatic patients before they underwent coronary angiography. In 44 patients with typical angina the combination of the three noninvasive tests and the exercise test alone both detected 92% of subjects with clinically important coronary artery disease. In 60 patients with atypical angina, the combination of the three noninvasive tests screened 77% of the subjects with clinically important coronary artery disease versus 43% after exercise test only (P less than 0.001). The exercise electrocardiogram was false negative in a substantial number of patients with atypical angina due to the presence of a good coronary reserve or to a daily circadian variation in the tone of the coronary arteries. Under these circumstances, cardiac cinefluoroscopy gave additional anatomic information to the physiological assessment of ischemia provided by the exercise test and ambulatory ST-segment monitoring. Our study suggests that the combination of cardiac cinefluoroscopy with other noninvasive tests may be particularly useful in screening atypically symptomatic populations. PMID- 4044070 TI - Pharmacokinetics of piperacillin in hospitalized patients. AB - Piperacillin is an extended-spectrum penicillin active against Pseudomonas. It has been documented to be effective in the treatment of complicated urinary tract infections and urosepsis. Much of the pharmacokinetic information available is obtained from normal subjects. The purpose of this study is to evaluate piperacillin pharmacokinetics in hospitalized patients. Ten clinically stable hospitalized urology patients were given 4 grams of piperacillin intravenously in a single dose. Serial blood samples were then obtained and serum piperacillin concentrations were determined by high performance liquid chromatography. The following pharmacokinetic parameters (mean +/- SD) were determined: half-life = 1.09 +/- 0.31 h, elimination rate constant = 0.69 +/- 0.22 h-1, volume of distribution = 0.36 +/- 0.13 l/kg, total body clearance = 0.230 +/- 0.054 l/h/kg. These parameters are comparable to those obtained in normal subjects except for the volume of distribution which is slightly higher than that reported in healthy volunteers. Pharmacokinetic information obtained in healthy subjects may, therefore, be applied to the clinically stable hospitalized urology patient. However, changes in pharmacokinetic characteristics may be found in the critically ill patient with compromise in hemodynamics and significant third spacing of fluid. PMID- 4044071 TI - A pharmacokinetic study of cefoperazone. AB - A pharmacokinetic study of cefoperazone on rats showed long half-life in serum and kidney. The most remarkable finding was that the drug was not detected in the fraction of mitochondria and lysosomes in all the experiment animals. The finding suggests the low nephrotoxic characteristics of cefoperazone. PMID- 4044072 TI - Sorbitol induced diarrheal illness model. AB - Twenty-five normal volunteers participated in this study to develop a model of diarrheal illness. The ideal model would induce diarrhea with consistent onset of 18 to 24 hours duration of watery stools, and have few associated symptoms. Groups of five to six each were studied. Volunteers who received castor oil experienced watery stools of short duration associated with abdominal cramps, making it an unacceptable model of disease. Sauerkraut and prune juices inconsistently caused watery stool. Seventy percent sorbitol induced watery diarrhea with few associated symptoms, and of five to six hours duration. The administration of 45 ml of 70% sorbitol six hours apart induced watery stools that met our objective and should be a suitable model for future drug testing of anti-diarrheal medications. PMID- 4044073 TI - Hemodynamic and pharmacokinetic study of propranolol and atenolol in cirrhosis patients. AB - The pharmacokinetic properties of propranolol and atenolol were evaluated both in 9 patients with cirrhosis and in 12 healthy subjects. The hemodynamic effects of the drugs were evaluated separately in the cirrhotic patients. Propranolol and atenolol significantly decreased wedged hepatic venous pressure and cardiac output in cirrhotic patients. Propranolol Cmax, tmax and AUC were significantly increased and plasma half-life was significantly prolonged in cirrhotic patients. In contrast, the corresponding pharmacokinetic values of atenolol were not significantly different in cirrhotic patients and in healthy subjects. PMID- 4044074 TI - Influence of food on the rate and extent of absorption of theophylline after single dose oral administration of a controlled release tablet. AB - Rate and extent of absorption of theophylline were determined in 7 healthy volunteers on pre- as well as on postprandial administration of commercially available controlled release tablets (Theograd-350 mg). In fasting subjects, maximum serum theophylline concentrations of 3.8 +/- 1.2 mg X 1(-1) (mean +/- SD) were reached at 3.4 +/- 1.2 hours after dosing, whereas under non-fasting conditions maximum serum levels of 5.8 +/- 1.3 mg X 1(-1) were found at 7.4 +/- 1.4 hours after the tablet was given. The bioavailability increased from 65 +/- 8%, observed on preprandial administration to 87 +/- 14%, when Theograd-350 mg tablets were taken after a meal. In conclusion, Theograd-350 mg tablets have a predictable absorption and give relatively high (87%) bioavailability, if the tablets are taken after a meal. PMID- 4044075 TI - Changes in plasma high density lipoproteins (HDL) levels after salbutamol. AB - Administration of salbutamol--in a single dose of 0.5 mg i.v. and in a dose of 8 mg twice daily during two weeks--was associated with an increase of HDL cholesterol concentration in the serum of patients with chronic bronchitis and severe airway obstruction. At the end of the second week of oral treatment with salbutamol, the HDL-cholesterol concentration in serum increased by 6.9% (p less than 0.01). PMID- 4044076 TI - Model independent pharmacokinetic study of cis-dichlorodiammineplatinum (II). AB - The disposition of cis-dichlorodiammineplatinum (CDDP) was evaluated in 8 patients with cancer. They received 80 mg/m2 of CDDP as a 20 min i.v. infusion. Sixteen blood samples and sixteen urine samples were obtained over 6 hours following the completion of cis-platinum infusion and were assayed for total platinum by flameless atomic absorption spectrometry. There was a great variation among maxima urinary concentrations (123 to 1436 mumol . l-1) and an important decrease of diuresis appeared 3 hours after the infusion. Model independent pharmacokinetic parameters: distribution volume and renal elimination clearance were determined. The calculated distribution volumes suggest an extremely rapid diffusion of CDDP into the peripheral compartment. The ratio of total platinum clearance to creatinine clearance decreased 75 min after infusion, this being the consequence of the variation of protein binding or nephrotoxicity. PMID- 4044077 TI - Pharmacokinetics of Josamycin in patients with liver cirrhosis and Gilbert's syndrome after repeated doses. AB - The pharmacokinetics of Josamycin was studied in 31 subjects (10 normals, 9 Gilbert's syndrome and 12 compensated liver cirrhosis) after the administration of Josamycin (1 g orally) and in 13 subjects (4 normals, 4 Gilbert's syndrome and 5 compensated liver cirrhosis) after 3-day Josamycin treatment (1 g orally every 12 hours). Josamycin pharmacokinetics was impaired in liver cirrhosis and, to a lesser extent, in Gilbert's syndrome. Moreover, in the three groups of individuals studied the drug accumulated after multiple dosing. These results suggest that a dosage adjustment of Josamycin is recommended when dealing with these patients. PMID- 4044078 TI - Methadone-maintained mothers: 3-year follow-up of parental functioning. AB - A group of 57 methadone-maintained mothers and 31 matched drug-free controls were compared on their ability to provide adequate child care, capacity for satisfying interpersonal relationships, and motivation for self-improvement. Results indicate that, as a group, methadone mothers require more assistance in parenting, are more socially isolated, and are less likely to pursue vocational and educational activities. The interpersonal and environmental impact of poor parenting further compounds the effects of in utero exposure to methadone, placing these infants at high risk. PMID- 4044079 TI - The intervention approach to drunk driver rehabilitation. Part I. Its evolution, operations, and impact. AB - In the campaign against drunk driving, the "third-generation" Weekend Intervention Program (WIP) met its clinical goals and was superior to education and treatment programs when treating DWI recidivists. Even in the face of the harsher legal climate in the case of WIP, this new intervention approach produced a lower recidivism rate than the control group. These positive findings suggest the need for further research with larger cell samples. PMID- 4044080 TI - The intervention approach to drunk driver rehabilitation. Part II. Evaluation. PMID- 4044081 TI - A longitudinal study of marijuana effects. AB - One hundred regular marijuana users volunteered to be extensively interviewed in 1968-1970, and 97 were located and reinterviewed 6 to 8 years later. As part of each interview the subjects filled out a checklist review of 105 effects of marijuana. This report focuses on the differential patterns of effects found at the two time intervals. Scores on groupings of items were examined for changes over time. Reports of sensory and hallucinatory items dropped substantially. Reports of appetite effects, sex effects, and intoxication effects on sleep remained stable. Reports of cognitive effects, mood effects, and aftereffects on sleep appeared to be shifting from desirable to undesirable, with the frequency of desirable effects dropping while frequency of undesirable effects remained the same. PMID- 4044082 TI - A clinical approach to the impaired health professional. AB - In recent years it has become abundantly clear that health professionals are at high risk for addiction to drugs and alcohol. Addiction is here defined as compulsion, loss of control, and continued use in spite of adverse consequences. Obviously health professionals with these symptoms are dangerous both to themselves and to their patients. Destigmatization at the community level, identification of addicts, intervention, and diversion into treatment are important factors in dealing with the problem. Programs for diversion and support are being developed in California for impaired physicians, nurses, and pharmacists. These are replicable elsewhere for helping impaired health professionals. PMID- 4044083 TI - Quantified human smoking behavior among various disease categories. AB - The present study reports the various quantified aspects of smoking behavior among patients (N = 244) with seven primary diagnostic categories; namely, neoplasms, endocrine, blood, circulation, respiratory, digestive, and GU. The study results indicate that patients with neoplasms and respiratory patients had longer puff durations than those in the other diagnostic categories. Patients with circulatory problems took longer to smoke a cigarette than patients with other diseases. Furthermore, patients with neoplasms tended to have higher tar delivery per cigarette than patients with other diseases. Finally, endocrine patients had the highest level of nicotine delivery per cigarette, with neoplasms and respiratory patients at the lowest level. These findings suggest a need for quantifying smoking behavior among patients of different disease categories in further studies. PMID- 4044084 TI - A test of nonrespondent bias in a family-based study: a research note. AB - The increasing use of family samples from "normal" populations (as opposed to clinical samples) in substance abuse research raises concern about the validity of responses from participating families. Nonparticipating families may have greater numbers of substance users who wish to conceal problems, when compared to families which cooperate with researchers. Unobtrusive analyses of institutional records of a health maintenance organization comparing families agreeing to participate in a substance use study (N = 508) with those families unwilling to participate (N = 538) reveal no significant differences in the use of chemical dependency services between the two groups. Surveys of the non-participating families indicate that the major reasons for noncooperation were the lack of time and inconvenience in getting family members together. These findings suggest the feasibility of sampling families from normal populations. PMID- 4044085 TI - The interface of drugs, genetics, and man. Part I. Drug actions/effects, manner of use, organismic factors, and ethical issues and considerations. PMID- 4044086 TI - The discouragement of smoking in a hospital setting. AB - Attitudes toward smoking among hospital patients and employees, smoking rates in specified areas, and the sales of tobacco products were assessed prior to a hospitalwide smoking discouragement program. Discouragement efforts consisted of the distribution of antismoking posters, educational materials, and displays, and placement of signs on the hazards of smoking at all hospital entrances and at the points of sale of cigarettes in the hospital canteen. Results show some significant decreases in the sale of tobacco products, changes in attitudes to become more critical of smoking, and changes in the smoking rate in the canteen eating area and main lobby. PMID- 4044087 TI - Intervention models for adaptation in a world of chemicals: a values approach. AB - A schema is presented designed to help intervention agents and agencies plan and carry out programs to facilitate individual and group adaptation to and within a world of an increasing variety of types of chemicals through selected value foci. PMID- 4044088 TI - Extended immunosuppression with cyclophosphamide using controlled-release polymeric implants. AB - An effective method of prolonged immunosuppressive therapy using cyclophosphamide incorporated into acrylic bone cement has been developed. We have studied the effect of this form of administration of cyclophosphamide on circulating immune cells and the inflammatory response. When the slow release mode of cyclophosphamide administration was compared with conventional systemic therapy, it was found to produce a more rapid and prolonged immunosuppression. A dose response relationship was established and the biological effects of varying the composition and surface area of the implant were determined. The inflammatory response, assessed by measuring the mobilisation of cells into subcutaneously implanted sponges, was also depressed using this mode of administration. These results, coupled with the commercial availability and existing clinical approval of Simplex P bone cement, suggest that the procedure could lead to useful clinical protocols. PMID- 4044089 TI - The immunological activity of plant toxins used in the preparation of immunotoxins--II. The immunodepressive activity of gelonin. AB - The immunological activity of Gelonin, a 30,000 dalton plant protein possessing close similarity to Ricin chain A as a protein synthesis inhibitor which may be of interest for the preparation of antibody-toxin conjugates, was studied in mice. At in vitro concentrations not affecting baseline radioactivity uptake, this substance reduced mitogen responses with the following order of sensitivity PHA less than ConA less than LPS. In microgram/ml concentrations it also markedly reduced macrophage-dependent cytotoxicity while not affecting NK activity. Macrophagic (but not NK) cytotoxicity and mitogen responses were similarly depressed after in vivo treatment. When given before (but not after) stimulus, Gelonin also reduced the primary responses to a T-dependent and, although to a lower degree, to a T-independent antigen, and decreased resistance to allogeneic tumor grafts and L. monocytogenes challenges. The immunopharmacological activity of this and similar substances should be considered in the design of antibody toxin conjugates and in the evaluation of their therapeutic activity. PMID- 4044091 TI - Regulation of histamine receptor concentration on human PBMC by homologous hormone. AB - Human peripheral blood mononuclear cells (PBMC) preincubated with 10(-3)M histamine at 37 degrees C, washed and incubated with 3H-histamine showed a reduction in the binding of the labelled hormone as compared to cells which had not been pretreated with histamine. Using competitive binding assays it was further shown that the number of specific binding sites for histamine was reduced by 46-62%. However, the affinity of receptors as indicated by Kd values remained unaltered. It would thus appear that elevated levels of histamine lead to down regulation of histamine receptors on human PBMC with a quantitative reduction in the number of binding sites without an alteration in their affinity characteristics. In view of the fact that histamine receptors have been shown to be present on suppressor lymphocytes, the down-regulation of these receptor sites may have relevance in physiological and disease states where perturbations in the levels of histamine are observed. PMID- 4044090 TI - Effect of thymosin alpha one on specific antibody response and susceptibility to infection in young and aged mice. AB - The antibody response to a variety of antigens has been shown to diminish with age. We investigated the capacity for Thymosin Alpha One (T alpha 1) treatment to augment antibody production in tetanus toxoid (TT) and pneumococcal capsular polysaccharide (PN) inoculated young and old mice. We also measured survival of these immunized mice after aerosol exposure to Streptococcus pneumoniae. As predicted antibody response to TT, but not PN, was significantly reduced in the old animals and T alpha 1 augmented antitetanus antibody in both young and old mice. T alpha 1 did not have an effect on anti pneumococcal antibody production. All mice that had received PN did have an antibody response, yet survival after exposure to the organism was strikingly less in the old animals. Our data support the contention that antibody response to T-dependent antigens (such as tetanus toxoid) falls with aging but can be reconstituted somewhat by thymic factors. Furthermore, for T-independent antigen (such as pneumococcal capsular antigens) the age-related changes are less evident. In the latter situation, the presence of a brisk antibody response after vaccination was not sufficient to prevent pneumonia and death in old animals. PMID- 4044092 TI - Characterization of histamine H-1 receptors on human mononuclear cells. AB - Histamine H-1 receptors on peripheral human mononuclear cells were characterized by radioligand binding of the H-1 receptor antagonist [3H]pyrilamine to lymphocyte-rich preparations. Simultaneous computerized analyses of sixteen separate equilibrium-binding assays indicated the presence of two distinct classes of binding sites with dissociation constants (Kds) of 4 +/- 1 nM and 55 +/- 9 microM and binding capacities of 21 +/- 7 fmol and 117 +/- 15 pmol/million cells, respectively. Competition binding curves for displacement of [3H]pyrilamine binding by histamine receptor agonists and antagonists also indicated the presence of multiple binding sites for the H-1 receptor. Further, the ED50 values determined for histamine receptor agonists and antagonists were entirely consistent with the expected rank order of potency for interactions with H-1 receptors. Thus, human mononuclear cells have a large number of H-1 receptors that exhibit two distinct binding sites, and the Kds for these sites are within the range of histamine concentrations achieved either in physiologic states or after mast cell (or basophil) degranulation. PMID- 4044093 TI - Iota-carrageenan induced reaginic antibody production in the rat--I. Characterisation and kinetics of the response. AB - The intraperitoneal injection of graded amounts of ovalbumin into inbred PVG strain rats was found to produce a dose dependent anti-ovalbumin antibody response without eliciting the production of ovalbumin-specific reaginic antibodies. The injection of ovalbumin admixed with iota-carrageenan enhanced the anti-ovalbumin response and simultaneously elicited the de novo production of reaginic anti-ovalbumin antibodies. Isotype analysis of the anti-sera revealed the presence of both IgG and IgE class anti-ovalbumin antibodies and demonstrated that non-reaginic IgE anti-ovalbumin antibodies were also a feature of this reaction. The reaginic antibody phase of the response, although transient in nature, was re-elicited by secondary antigen challenge. The administration of ovalbumin prior to the ovalbumin-carrageenan preparation was shown to abrogate the reaginic antibody response without significantly influencing the non-reaginic component of the response. Conversely the injection of iota-carrageenan prior to antigen, significantly suppressed the normal agglutinating anti-ovalbumin response but did not prevent the induction of reaginic antibodies. These observations demonstrate that iota-carrageenan can, under specific conditions, function as an efficient adjuvant, and is capable of by-passing the normal mechanisms responsible for controlling antigen specific reaginic antibody production. PMID- 4044094 TI - Opposite effects of cyclophosphamide pretreatment on tuberculin hypersensitivity during the course of sensitization of mice with Mycobacterium bovis BCG. AB - The influence of cyclophosphamide (CY) pretreatment upon the development of tuberculin hypersensitivity has been studied during the course of infection of mice with BCG. An enhancement of the DTH response to BCG antigens occurred during the induction phase, whereas a depression of this response occurred at the peak and during the decay phase of sensitization. The development of the early DTH promoting and of the late DTH-depressing effect of CY was favoured by the use of a supra-optimal dose of BCG. Both these effects were cell-dependent since they could be transferred adoptively to syngeneic recipient mice with sensitized lymphoid cells but not with specific immune sera. Pretreatment with CY favoured the emergence of cells capable of responding in vitro to BCG antigens in the draining lymph nodes of BCG-infected mice. No simple association however, exists between this in vitro lymphocyte transformation response and the DTH response. PMID- 4044095 TI - The serum pharmacokinetics of digoxin as an immunogen and hapten in the rabbit. AB - 3H-digoxin was given intradermally 4 weeks before, and at 6 and 44 weeks after immunisation with a 3H-digoxin-human serum albumin conjugate. Before immunisation, the serum digoxin distribution and elimination half-life (t1/2) values were 4.2 h and 2.1 days respectively. The immunogen-associated radioactivity showed characteristic fluctuations during a prolonged distribution phase of about 5 days, but the t1/2 of 2.7 days was similar to that of digoxin, indicating that appreciable cleavage of digoxin from the albumin may have occurred during the distribution period. At 6 weeks after immunisation, following hapten injection there was again a prolonged distribution phase of about 5 days during which concentration of digoxin were some five-fold higher than corresponding pre-immunisation values. The serum elimination t1/2 was 4.1 days. At 44 weeks the differences were even more marked; the distribution phase was some 7 days, during which serum hapten concentrations were approximately ten-fold higher than pre-immunisation values. The serum elimination t1/2 was in this case about 25 days. Surprisingly digoxin-specific antibody titres at 6 and 44 weeks were not significantly different, indicating that measurement of titre, which is a function of both antibody concentration and affinity, is not in itself reliable in predicting changes in hapten pharmacokinetics. PMID- 4044096 TI - A comparison of the effects of hydrocortisone on peritoneal inflammatory exudates, the tuberculin reaction and contact sensitivity-to DNFB in the guinea pig. AB - Hydrocortisone acetate, injected subcutaneously in five doses in a depot producing vehicle, causes prolonged suppression of the ability of guinea pigs to produce a chronic inflammatory reaction in the peritoneal cavity and also of the tuberculin reaction. This suppression of the tuberculin reaction persists for at least 65 days after the last dose of hydrocortisone. Suppression of both peritoneal exudate and the tuberculin reaction was associated with a preferential depletion of macrophages at the reaction site. A similar regime had no effect on the ability of guinea pigs to manifest contact sensitivity reactions to 2,4 dinitrofluorobenzene although there was a similar drop in macrophages in the lesion. It appears that the effect of hydrocortisone on delayed hypersensitivity reactions is not directly related to the functional contribution of macrophages in the inflammatory reactions, and may be related to the site of the inflammatory reaction in the skin. PMID- 4044097 TI - A synthetic vaccine against influenza with built-in adjuvanticity. AB - In a previous publication we demonstrated that an anti-viral response against influenza can be achieved by immunization with a conjugate of the synthetic peptide corresponding to the sequence 91-108 of the hemagglutinin, when administered in complete Freund's adjuvant. In the present study we compare the adjuvant activity of the synthetic MDP with that of CFA and alum, in the above mentioned immunological system. The level of anti-peptide antibodies raised by the three adjuvants was similar, with only slight variations, yet, only CFA led to significant cross reaction with the virus. Nevertheless, MDP, when linked covalently to the conjugate (91-108)-TT was an efficient substitute for CFA in inducing anti viral protection against in vivo challenge infection. The administration of free MDP in a mixture with the peptide-toxoid conjugate did not lead to a significant protection. PMID- 4044098 TI - Effect of lentinan on the chemiluminescence produced by human neutrophils and the murine macrophage cell line C4M phi. AB - Lentinan, an immunopotentiating polysaccharide, stimulates the production of chemiluminescence (CL) by human neutrophils and the murine macrophage cell line C4M phi. The CL enhancing effect of lentinan opsonized in human serum is greater than that of lentinan itself. Lentinan's stimulation of neutrophil CL was increased by 1/2 when opsonized in human serum inactivated at 56 degrees C to remove complement, while the CL was increased two fold by lentinan opsonized in whole serum. This indicates that C3b and immunoglobulin contribute separate signals in the activation process mediated by opsonized lentinan. The distinct roles of the C3b and Fc receptors was further illuminated by the finding that an Fc receptor-negative cell line was unresponsive to lentinan opsonized in heat inactivated serum (56 degrees C), whereas it exhibited a five fold increase in CL in response to lentinan opsonized in serum containing complement. Lentinan in an opsonized form can stimulate the production of CL via C3b and Fc receptors. This mechanism may be considered as one mode of action of lentinan and other similar immunopotentiating and antitumour glucan-type polysaccharides. PMID- 4044099 TI - Depression of Con A proliferative response of immune cells by in vitro hyperoxic exposure--protective effects of thiol compounds. AB - Time dependent response for hyperoxic exposure was determined in vitro on ConA proliferative response of rat splenocytes, peripheral blood mononuclear cells and thymocytes. The proliferative responses were evaluated after different lengths of hyperoxic exposure (12-72 h, FiO2 = 0.95). After 24 h oxygen exposure, the spleen cell viability assessed by dye exclusion was normal but DNA synthesis was markedly suppressed in the above three types of cells. Total or partial protection of the mitogenic response to ConA was obtained by 2-mercaptoethanol, reduced glutathione or L-cysteine addition in culture medium; only selenomethionine had no protective effect. Thymic cells showed a different response-curve: after 6 h exposure to normobaric oxygen DNA synthesis was decreased and was not restored by any of the thiol compounds tested. In this respect, these cells demonstrated different susceptibility to an oxidant injury, i.e. exposure to high oxygen concentration. From a pharmacological point of view O2 exposure and altered immune response could be proposed as a useful model for screening the antioxidant drug activity. PMID- 4044100 TI - Thymosin alpha 1 exerts protective effect against the 5-FU induced bone marrow toxicity. AB - Thymosin alpha 1 was shown to prevent the 5-fluorouracil(5-FU)-induced bone marrow toxicity in BDF1 mice, as determined by the cellularity, haemopoietic stem cells (CFU-s) and granulocyte-macrophage colony forming unit (GM-CFU). Furthermore, thymosin alpha 1 increased the levels of colony stimulating factor (CSF) in sera or in culture media of spleen cells derived from 5-FU-treated mice. The treatment of spleen cells with anti-Thy 1,2 antibody plus complement abolished completely the CSF production. The in vivo treatment of donor mice with anti-Thy 1,2 antibody following 5-FU abolished completely the capability of their bone marrow cells to save lethally irradiated recipients. Thymosin alpha 1 treatment prevented the damage by such combined treatment. The present study indicates that thymosin alpha 1 exerts its protective effect against the 5-FU induced bone marrow toxicity, at least partially, through its effect on the maturation of immature T cells to functional T cells which produce various kinds of lymphokines including CSF. PMID- 4044101 TI - In vitro inhibition of the activation of the human complement and coagulation systems by chloroquine. AB - The ability of chloroquine to inhibit the activation of the complement and coagulation systems was investigated. The activation of the classical pathway of complement by antibody coated sheep erythrocytes and aggregated IgG was blocked by chloroquine. Similarly, it prevented normal rabbit erythrocytes and zymosan from activating the the alternative pathway of complement. The activation of C3 by immune complexes of different solubilities also was inhibited by this drug. In addition, it abrogated the clotting of plasma by calcium chloride and thrombin. This effect could be reversed by the addition of excess thrombin but not of calcium chloride. It is suggested that the inhibition of these two important phlogistic mediator systems of inflammation may contribute to the anti inflammatory property of chloroquine. PMID- 4044102 TI - Prediction of maximal effort bicycle ergometer endurance performance. AB - Fifteen competitive cyclists and 15 subjects not involved in competitive cycling were studied to determine the relationship between VO2max, lactate threshold (LT), fixed blood lactate concentrations, body composition parameters, and maximal effort bicycle ergometer performance. The subjects were assessed for VO2max, LT, VOLT, and VO2 associated with blood lactate concentrations of 3, 4, 5, and 6 mM/l (VO2 3 mM-VO2 6 mM/l), using an incremental protocol on the bicycle ergometer. Body composition was determined by underwater weighing. Subjects also completed two 10-min drop-off performance tests (starting at 70 rpm) at the same absolute power output (4.5 kg resistance, 1890 kgm/min) (ABS) and at the same relative power output (the highest power output completed for 3 min on the VO2max test) (REL). Metabolic measures and revolution scores were collected on a minute by-minute basis during the performance tests. The results indicated that the competitive cyclists had higher VO2max (4.25 +/- 0.39 vs 3.50 +/- 0.54 l/min); VO2 LT (2.91 +/- 0.55 vs 1.66 +/- 0.49 l/min); VO2 3 mM, VO2 4 mM, VO2 5 mM, VO2 6 mM, VO2 LT/VO2max (68.5 +/- 11.2 vs 47.2 +/- 10.9 %); max resistance (5.70 +/- 0.56 vs 4.63 +/- 0.67 kg); and resistance at LT (3.57 +/- 0.70 vs 1.93 +/- 0.68 kg) as compared to the noncompetitive subjects (P less than 0.05). Correlational analysis revealed poor prediction between metabolic measures and the homogeneous cumulative rpm scores during the REL test.2+ subjects (r = 0.60 to 0.90).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4044103 TI - Variability of aerobic performance in the laboratory and its physiologic correlates. AB - To study the physiologic basis of variability of physical performance in the laboratory, ten male subjects were studied once a week, during a 9-12 month period. Previously, the reference maximal work load attained (Wref) was determined in each subject. The test protocol of the actual study was based on the individual Wref and started at 70% Wref for 5 min whereupon the work load was increased by 5% Wref every 2.5 min to exhaustion. The maximal work load attained (Wmax) was considered as the test performance. Heart rate, respiratory variables, oxygen uptake (VO2), and blood lactate concentration were determined at each work load. The rate of perceived exertion during submaximal and maximal work was also scored. In all subjects, Wmax and VO2max varied randomly, while the coefficient of variation in VO2max (4.20% - 11.35%) exceeded that in Wmax (2.95%-6.83%). No seasonal influences on VO2 max and Wmax were observed. In all subjects the physiologic variables, when plotted as a function of external work load, were shifted to the right with higher Wmax values and to the left with lower Wmax values. With lower Wmax values, the rate of perceived exertion during submaximal work tended to increase. The results suggest that the magnitude of physiologic responses to exercise is related to relative work load and that variability of physical performance is related to changes in gross mechanical efficiency. PMID- 4044104 TI - Influence of caffeine on blood lactate response during incremental exercise. AB - To test the hypothesis that caffeine ingestion prior to exercise would delay the onset of blood lactate accumulation, eight male subjects were studied during incremental exercise to maximal work rates on a cycle ergometer under two conditions: 1 h after ingestion of 200 ml of either decaffeinated, calorie-free cola (control trial) or the same cola drink with 5 mg caffeine/kg body weight added (caffeine trial). Maximal exercise values for oxygen consumption (VO2 max), ventilation, heart rate, respiratory exchange ratio (R), work rate, and blood lactate were not affected by caffeine. Submaximal exercise VO2, ventilation, and R also were unaffected by caffeine. During the caffeine trial, submaximal exercise blood lactate was significantly higher and heart rate significantly lower than during the control trial (P less than 0.05). The lower exercise heart rate at the same VO2 resulted in a significantly greater O2 pulse during all submaximal exercise intensities for the caffeine trial (P less than 0.05). Data on R indicated that caffeine had no effect on substrate utilization during exercise. Data on exercise blood lactate response suggested that caffeine does not delay and may accelerate the onset of blood lactate accumulation during incremental exercise. When defined as either a "breakpoint," delta l mM (above resting lactate), or fixed level of 4 mM, the lactate threshold (LT) did not differ between caffeine and control trials. However, in using a 2 mM lactate level as a criterion, the LT during the caffeine trial (2.13 +/- 0.22 l X min-1) was significantly (P less than 0.05) lower than during the control trial (2.71 +/ 0.17 l X min-1).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4044105 TI - Insulin sensitivity in joggers: evaluation by mini-dose insulin infusion test. AB - Insulin sensitivity in seven joggers was evaluated by a minidose insulin infusion test. The results were compared to those of 22 healthy nonjoggers with a mean body weight within +/- 115% of ideal body weight. The mean increase over base line of the individual steady-state insulin levels were delta 25 microU/ml (range 15-42 microU/ml) for controls and delta 16 microU/ml (range 11.2-23.4 microU/ml) for the joggers. The smaller incremental rise in insulin concentration most likely is due to an increased insulin turnover. The declines in glucose concentrations from 10 min after the infusion began to a nadir were similar in controls (28 +/- 2.4 mg/dl) and in the joggers (33.7 +/- 3.6 mg/dl). However, the insulin sensitivity index, defined as the rate of plasma glucose decline divided by the increment rise in insulin, was clearly higher in the joggers (0.098 +/- 0.009 vs 0.057 +/- 0.005, P less than 0.05). We conclude that the joggers as a group are more sensitive to insulin. The simplicity of a mini-dose insulin infusion should be useful in longitudinal studies where the effect of physical training on insulin sensitivity may be of interest. PMID- 4044106 TI - Effects of endurance training on the androgenic response to exercise in man. AB - Six healthy subjects, aged 35.8 +/- 4.4 years, volunteered to participate in a 40 week training program on a bicycle ergometer [three 60-min sessions per week at 80%-85% of maximal oxygen uptake (VO2 max)]. Before training and at the 10th, 20th, 30th, and 40th weeks of the training program, plasma testosterone, cortisol, and androstenedione concentrations were measured at rest (t0) and at the end (t60) of a 1-h endurance exercise requiring 85%-90% of VO2 max. Training resulted in significant increases of anaerobic threshold (12.6%) and VO2 max (7.3%). The training program did not significantly alter the resting values of plasma testosterone, androstenedione, and cortisol; in contrast, the exercise responses (delta = t60-t0) of testosterone, androstenedione, and cortisol were increased. The highest amplitude of these responses was reached at the 30th week for cortisol and androstenedione and at the 40th for testosterone. These results suggest that long-term training enhances both testicular adrenal and responses to endurance exercise. The possible role of hormonal changes in the mobilization of energy substrates during exercise is discussed. PMID- 4044107 TI - Heart rate break point may coincide with the anaerobic and not the aerobic threshold. AB - Recently, Conconi et al. (4) proposed that the point where heart rate departs from linearity in an incremental exercise test is a good predictor of the aerobic threshold (AeT, i.e., the exercise intensity at which blood lactate concentration increases systematically above resting levels). We hypothesized that this heart rate break point (BrP) is a better predictor of the anaerobic threshold (AnT, i.e., the exercise intensity at which blood lactate concentration shows a rapid rise during an incremental test). To test this hypothesis, 11 subjects with different levels of conditioning were tested on a cycle ergometer using a progressive incremental exercise protocol. Heart rate from EKG tracings and blood samples for lactate determination were taken every minute. The results showed the following significant correlation coefficients when the variables were expressed in watts: AeT and AnT = 0.92; AeT and BrP = 0.89; AnT and BrP = 0.97. The AeT was significantly lower than the BrP (166.4 +/- 52.6 W and 234.5 +/- 69.5 W). There was no significant difference between the AnT and BrP (240.0 +/- 67.1 W and 234.5 +/- 69.5 W). Another group consisting of 16 subjects performed two tests to evaluate the reproducibility of the BrP. Although a ventilatory AnT (defined as a consistent decrease in the fraction of expired CO2) was noted in all the tests, eight subjects failed to demonstrate a BrP in at least one of the evaluations, even though post-exercise blood lactate levels and peak heart rates were consistent with a maximal effort.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4044108 TI - Physiologic changes in rowing performance associated with training in collegiate women rowers. AB - To evaluate the physiologic changes in rowing performance during the training season, selected cardiorespiratory variables were measured three times at 3-month intervals in seven collegiate women rowers during incremental exercise on the rowing ergometer. Values for maximal oxygen consumption (VO2 max) and peak power production increased by 14% and 18%, respectively, over the 6-month period. Maximal heart rate was unchanged with training. Oxygen-pulse increased significantly (+ 14%) during the training season, while the ventilatory equivalent for oxygen did not change. Oxygen consumption as a percent of VO2 max and heart rate at the anaerobic threshold (AT) decreased during the first 3 months of predominantly aerobic training, but increased significantly in the last 3 months with greater anaerobic conditioning. The changes demonstrated by physiologic testing corresponded to the particular type of training emphasized during the 6-month period. Serial measurements of VO2 max and AT can be used to assess the benefits of specific training. Based on these results, individual guidelines for aerobic and anaerobic conditioning can be developed using the heart rate response at the AT. PMID- 4044109 TI - Effect of boxing on some metabolic indices of muscular contraction. AB - Muscular contraction, especially if it is protracted or particularly intense, causes notable changes in the substrate and enzymes involved. Marked changes have been found in the serum levels of myoglobin and CK in individuals subjected to very stressful physical work. This phenomenon has usually been attributed to the repeated and intense muscular traumas inherent in certain sporting activities. In the light of these facts, the authors decided to perform a study on amateur boxers aimed at measuring the difference between simple muscular work (shadow boxing) and traumatic activity (real boxing) in terms of their effect on a number of humoral parameters, especially myoglobin and CK. The serum levels of these two latter substances were found to increase more after real boxing than after shadow boxing. PMID- 4044110 TI - Southwest Chapter--American College of Sports Medicine. Las Vegas, Nevada, November, 1984. Abstracts. PMID- 4044111 TI - Importance in training physiology and clinical importance of anaerobic capacity. International congress. St. Johann, Tyrolia, 19-21 September 1985. Abstracts. PMID- 4044112 TI - Sheep in wolf's clothing: impact of normalisation teaching on human services and service providers. AB - A historical review of the development of the normalisation concept is undertaken, with an appraisal of the various historical contributions. The underlying assumptions, research foundations and methods of information transmission are examined with respect to implications for the concept. A critically evaluative stance is recommended in order to assess the utility and validity of normalisation beyond a position of moral principle and sloganeering. Some possible consequences of normalisation advocates who maintain an inflexible position in this debate are identified, together with some recommendations for an alternative perspective. PMID- 4044113 TI - Physico-mechanical aspects of decubitus prevention. AB - Reviewed is the theory of tissue deformation as cause of decubitus, as developed in cooperation with two Dutch Rehabilitation Institutes and two Dutch Rehabilitation Research Institutes. Also reviewed are the conditions of the prevention of decubitus concerning the support of the human body in the lying situation. The consequences of the new anti-deformation theory for the lying support are discussed. A classification is given of the existing lying-down support systems. Examples of the three categories of existing lying-down support systems are given and discussed in general. PMID- 4044115 TI - The Society for Research in Rehabilitation. Proceedings of scientific meetings, 1984. Abstracts. PMID- 4044114 TI - Children at-risk: child abuse in Denmark. AB - In Denmark there have been few case reports on child abuse, but only one epidemiological study conducted in 1969. We have therefore initiated a number of countrywide studies by contacting all pediatric departments, Institutes of Forensic Medicine and the public health officers in Denmark. The present study describes the findings from the city of Copenhagen during 1970-79. Only 27 children, mostly under seven years of age, were registered. Information on pregnancy, delivery, neonatal period and the children's former development provided significant findings. All the registered families belonged to the lowest social class, half of the children had a history of previous abuse, one third of siblings had also previously been abused and one third of the wives were "battered wives". In 2/3 of the cases the father-figure was the perpetrator. The study showed an urgent need for a more coherent policy on child abuse and child welfare, general guidelines on interdisciplinary work, communication, prevention, community work and follow-up. Practical guidelines for involvement with child abuse are proposed and it is recommended to establish child abuse teams in Denmark, also in order to deal with prevention at the pre- and postnatal level. The pediatric departments should get more involved with community and social work in order to deal with child abuse and neglect at an early stage, where the abuse can be prevented. PMID- 4044116 TI - Dermatology looks to the future. PMID- 4044117 TI - Changes of inner space. AB - This paper describes the relationship between the experiential aspects of the concept of inner space and of emptiness. This is based on the change of inner experience of a borderline patient during analysis from one of empty space to one of real space. The analysis is described and the relationship of inner space to schizoid and depressive emptiness elaborated, together with the emergence of a healthy inner space (positive emptiness). The components of the capacity to experience inner space from infancy onwards are enumerated and discussed. PMID- 4044118 TI - Cruelty and narrowmindedness. AB - The contention of this paper is that human understanding modifies cruelty, and that in order that cruelty can remain unmodified various mechanisms are employed. The most important processes include the worship of omnipotence which is felt to be superior to human love and forgiveness, the clinging to omnipotence as a defence against depression, and the sanctification of grievance and revenge. In order to avoid conscious guilt, the perceptions of the mind are narrowed to give ostensible justification to the cruelty, and the obviation of redeeming features in the object. The paper explores how these processes operate and how by virtue of projection the analyst's interpretations are perceived as cruel, and how the patient arranges to be locked in this vicious circle. Technical problems of dealing with these forces are explored together with the task of bringing alive the human concern that modifies cruelty. PMID- 4044119 TI - The female analyst and the erotized transference. AB - The concept of erotized transference is discussed from Freud's original writings on the subject to those of recent contributors. It is noted that there exists an almost complete absence of reports in the literature of male patients developing an erotized transference to their female analysts. The question of how significant the gender of the analyst is in the unfolding of the transference and its vicissitudes is raised. It is maintained that the four possible analyst/analysand dyads differ qualitatively in that resistance and identification in the transference may be enhanced or inhibited by the gender of the analyst and/or the homosexual or heterosexual nature of the dyad. The erotized transference to the female analyst is focused upon as a vehicle to the study of such qualitative differences. It is hypothesized that the expression of strong erotic urges to the female analyst by the male patient is somewhat inhibited by the fantasy of the overwhelming pre-oedipal mother. In contrast, such erotic feelings are freely expressed by the female patient. Two cases, a male and a female, are described to support the above hypothesis. PMID- 4044120 TI - On transference manifestations in male patients with female analysts. AB - The transference issues that are specific to the psychoanalysis of male patients by female analysts have not been widely discussed in the literature. Most of the literature on this subject has indicated, contrary to the findings reported here, that full and intense erotic transference manifestations are rarely if ever seen in this therapeutic dyad. In order to clarify the issues, we have offered some definitions that may serve as a framework for future discussions. We have utilized clinical examples from the psychoanalyses of five patients to illustrate certain aspects of the transference. We have demonstrated that male patients display a full range of erotic transference phenomena with female analysts and have focused attention on certain special features of these tranferences. For example, in some cases it was only after considerable analysis of defences against aggression that the erotic transference manifestations emerged fully. We have also shown that paternal transferences occur regularly, though they may be difficult to elucidate until the later stages of analysis. We have paid special attention to the feared loss of maleness that attends male patients' identification with their female analysts. PMID- 4044121 TI - The oedipal experience: effects on development of an absent father. AB - This paper discusses the effects on both child and adult when there has been a loss of the father through separation or divorce in the first five years of life. It is written with regard to the psychoanalytic treatment of individuals who have experienced such a loss of the father. The first part of the paper deals with the developmental effects on the child from the viewpoints of the pattern of oedipal development, superego structuralization, identification and sexual identification, and the analytic treatment process. The second part gives brief accounts of the analyses of two adults. It is proposed that while analysis of such patients may achieve a certain level of success, there may in some cases remain a relatively intractable degree of narcissistic interference and an impairment in their capacity to make an internal separation from the remaining primary object, the mother. PMID- 4044122 TI - 'Everybody must be just like me': observations on female castration anxiety. AB - The concept of primary femininity entails an assumption that the girl develops some mental representation of genital femaleness at an early age. I have suggested one form that such a mental representation may take and a particular expression of female castration anxiety that may develop in consequence. I have suggested that the young girl begins by assuming that everyone has a vulva like hers, with the possibility of an opening and the possibility of an inside space. Among the consequences of such an assumption may, in certain girls, be the development of a castration fantasy in which males represent the frightening possibility that such an opening in a female could be endangered, lost, or closed up as that opening is imagined to be in males. I have suggested that certain sterotypic features of the ways in which some women characterize men (i.e. men are emotionally closed, unable to be receptive, without access to inner feelings or sensitivities, etc.) may be understood at least in part as derivatives of this fantasy. PMID- 4044123 TI - Phantasy effects that which it represents. AB - This paper sets out to show that phantasy does not just inhabit a mental realm within the individual. With the help of some clinical examples, it tries to demonstrate that phantasy is itself an active agent, so that the image within the phantasy is brought into effect through a subtle stimulation of the social environment. The paper ends by suggesting the way in which this can happen. PMID- 4044124 TI - Family pathology and the infantile neurosis. AB - In this study we have attempted to investigate the connection (in the sense of a complex interplay) between the infantile and the adult neurosis where severe family pathology has been an important determining force. In the clinical illustrations of two female patients we tried to determine the fate (i.e. in terms of the compulsion to repeat) of the early infantile conflicts and experiences within the purview of their pathological family condition. In sorting this out, we distinguished between those repetitions viewed as passive reproductions and those repetitions viewed, as re-creative; the former finding their way essentially into the adult neurosis, the latter finding their way into parts of the personality under the aegis of their ego's organizing activity. The fashion in which the family pathology impinged upon the adult neurosis made the development of the transference in the analytic situation a most difficult arena for clarification, since there was a tendency to confuse past (early) events, past fantasy, current reality and current fantasy. In concluding we noted that both Oedipus complex and oedipal drama came together in these patients, revealing the link between the tragedy of their life-long family situation and what was termed a 'fate neurosis'. PMID- 4044125 TI - Acute coronary occlusion: oxygen pressure in the border zone studied in the pig. AB - The area between ischemic and normal myocardium after acute coronary occlusion the border zone-is of great interest. It has been proposed that this area contains reversibly damaged myocardium subjectable to myocardial salvage. Twenty Swedish land race pigs were studied, 13 after acute occlusion of the left anterior descending coronary artery (LAD), while seven served as controls. We measured tissue oxygen pressures (ptO2) subepicardially with the MDO electrode. This is a multiwire surface electrode measuring ptO2 with eight individual platinum wires. Hundred and twenty values were collected in each measuring situation. The electrode was positioned on the lateral border zone, measurements were performed before and 5, 30 and 120 min after LAD occlusion. In five cases successful measurements were performed across the border zone. A mixture of normal and ischemic ptO2 values was found 5 min after occlusion. After 30 min of occlusion the number of ischemic values decreased and this was particularly the case after two hours of occlusion. The results support the view that the border zone was very narrow. The reduced number of ischemic values after two hours of permanent LAD occlusion also indicated that the border zone may be narrow but not necessarily fixed but instead dynamic. In this case there was a spontaneous decrease of the ischemic area. PMID- 4044126 TI - Microscopic studies on the influence of erythrocyte concentration on the post junctional radial distribution of leukocytes at small venular junctions. AB - The influence of flow patterns and erythrocyte concentration on the post junctional radial position of leukocytes was studied in microvascular junctions in an isolated mesocaecum preparation and in vivo in the rat cremaster muscle. Main branch and side branch dimensions (mesentery) were approximately 60 micrograms and approximately 20 micrograms, respectively. For the analysis the main branch was divided into three equally wide sectors. Firstly, the observations indicate that the main branch and side branch flows remain separated downstream of a junction and, secondly, that the blood cells mainly leave the junction within their original streams. At zero hematocrit 71-87.5% of the leukocytes from the side branch flowed in the closest main branch sector; 12.5 29% reached the central sector-the lowest numbers were seen in the central sector when the flow velocity ratio, main branch-side branch was 2:1. No cells became marginated. At 20% and 40% hematocrit, all leukocytes from the side branch flowed in the closest main branch sector. Marginated leukocytes in the side branch or upstream in the main branch remained marginated only if passing the junction on the uninterrupted wall. In the cremaster muscle, 3-capillary confluences were studied. The blood from the capillaries seemed to flow in three separate streams in the venule. Since these streams were narrower than those observed in the mesentery, the leukocytes in the capillaries producing the peripheral streams continued to flow in contact with the vascular wall, i.e. they became marginated in the venules without any lateral movement. On the basis of this study and previous work it is proposed that the radial position of leukocytes downstream of a junction is determined not only by leukocyte-erythrocyte interactions but also by the specific flow patterns that arise in microvascular confluences. PMID- 4044127 TI - Differential vulnerability of male and female rats to the timing of various perinatal insults. AB - The results of five experiments showed that exposure to diazepam, hypoxia and monosodium glutamate during the prenatal or early postnatal period of rapid brain development may result in different behavioral consequences depending on the timing of the exposure rather than the nature of the agent. Moreover, male and female offspring may be affected differently by the same agent at different periods of development. Prenatal insults of various kinds impair the later performance of males but not the females in a complex learning task, while postnatal insults seem to affect detrimentally this same behavior in both males and females. The effects of perinatal insults on maze learning and open field activity do not lend themselves to explanation by "feminization" or "masculinization" of behavior caused by interference with prenatal gonadal hormones. PMID- 4044128 TI - Topography of the hemi-inattention syndrome. AB - The hemi-inattention syndrome was studied in 15 right-handed adults, 12 men and 3 women. One patient had a pontic-mesencephalic lesion, 3 had right hemisphere damage, 7 had left-hemisphere lesion and 4 had bilateral lesions. All lesions were confirmed by CT-scan. Different criteria of hemi-inattention were used. All patients presented extinction, inattention and in 13 visuomotor akinesia; 5 of the left and all of the right and bilateral lesion patients presented spatial neglect. CT-scans were superimposed. The posterior parietal region was the most important in producing contralateral hemi-inattention. Results are discussed with relation to the literature and the educational factor and cerebral asymmetry are discussed with regard to hemi-inattention. PMID- 4044129 TI - Effects of impeded breathing on auditory brainstem responses in conscious man. AB - Auditory brainstem responses (ABR) recorded in two groups of 10 normal volunteers were compared under conditions of impeded and unimpeded breathing. Impedance to breathing was accomplished by adding inspiratory flow-resistive loads of varying magnitude. Loaded breathing selectively augmented the amplitude of ABR components generated in the vicinity of the pontomidbrain junction. Peak latencies and other peak amplitudes of the ABR were unaffected. These findings suggest that the ABR procedure may serve as a direct noninvasive approach to the assessment of brainstem respiratory functions in conscious humans. PMID- 4044130 TI - Are lateral differences in word processing modulated by concreteness, imageability, both, or neither? AB - The classic right visual field superiority for the processing of words by normal subjects is reduced when stimuli are highly imageable or concrete. Given that these two properties are correlated, imageability and concreteness are tested separately in order to decide which is determinant. In the first experiment, 16 normal subjects were given a lexical decision task with laterally visually displayed stimuli (360 items); in the second experiment, 16 other normal subjects were given a task of reading laterally displayed words (180 items). In both experiments, the usual right field advantage emerged. It was affected neither by imageability nor by concreteness in the first experiment. In the second, the right field superiority appeared, except for highly imageable words, in males only, but this interaction was not clearly interpretable. Analysis of errors suggests that the right hemisphere could be sensitive to the imageability of words and the left to their concreteness. PMID- 4044131 TI - Memory characteristics in Parkinson's disease. AB - With regard to Parkinson's disease there are contradictory opinions concerning whether the severity of the disease, the patient's age, or the application of aids influence the patient's short term memory. In a 4 X 2 X 2 semifactorial design these conditions were tested on 24 healthy persons and 72 patients suffering from Parkinson's disease. The stimulus material consisted of 30 nouns belonging to 6 categories. The severity of the disease, the age of the patients, and the interaction between severity and assistance determined conditions of the patient's memory achievement. PMID- 4044132 TI - Behavior disorders and laterality of cerebral function. AB - A dichotic listening test was employed to test the hypothesis that behavior disorders might have an abnormal laterality patterns of cerebral function. Eighteen behavior disorder out-patients of the psychiatry department at an university hospital and seventeen normal subjects were requested to recall dichotically presented words. The results showed that compared with the normal controls, the subjects with behavior disorders yielded less prominent right ear advantage, lesser response ear alternations, but better overall performances. The results do not support the hypothesis of the left hemisphere dysfunction in behavior disorders but suggest the possibility of the right hemisphere dysfunction. PMID- 4044133 TI - Attention to television: intrastimulus effects of movement and scene changes on alpha variation over time. AB - Central and occipital EEG alpha were used as an on-line measure of momentary changes in covert attention during television viewing. Alpha was recorded during nine 30-second commercials shown embedded in a half-hour situation comedy. Two time series were constructed for data analysis. A stimulus series consisted of codes representing the presence or absence of scene changes or person and object movement for each half-second interval of the commercials. The alpha series consisted of median alpha scores for each half-second interval, aggregated across 26 subjects. The alpha series was regressed on the movement and scene change series, both of which produced significant increments in R, even after autocorrelational effects inherent in the alpha series were removed. As a validity check on the attentional interpretation of alpha, it was shown that mean alpha for each commercial was significantly (negatively) correlated with recall and recognition of commercial contents. The results are discussed in terms of their implications for further use of continuously-recorded alpha in research on factors that influence attention to television. PMID- 4044134 TI - Cortical visual evoked potentials during the sleep-wakefulness cycle in the freely moving cat. A dynamic study. AB - The dynamic features of visual evoked potentials, elicited by a light emitting diode chronically implanted in the frontal sinus of the freely moving cat, were studied during sleep stages by means of calculation of the power spectra of the EEG prior to the stimulus and the poststimulus EEG which contain the single evoked potential. The statistical analysis between mean frequencies from both EEG prior to the stimulus and single evoked potential, within each sleep stage, showed that the main changes occurred during slow sleep, with a significant increase in the percentage of the alpha band. These results are interpreted as a partial desynchronization evoked by the visual stimulation during the synchronized phase of sleep. PMID- 4044135 TI - Psychomotor decline can be described by discontinuities in response trajectories. AB - Force exerted in the isometric button-press response in a choice reaction time experiment was measured in order to study discontinuities in the response trajectory. Groups of young and elderly subjects were compared on performance with four choice reaction time tasks of varying difficulty. An additional comparison (with one task only) was made with a group of brain-damaged subjects. Velocity changes within the response trajectory were used to locate its discontinuities. The principal finding was that response discontinuities were least frequent in young subjects, intermediate in elderly, and most frequent in brain-damaged. Also, in the comparison of young and elderly across four stimulus conditions, the number of discontinuities was greater with more difficult than with easier tasks. Psychomotor decline was interpreted as an increase in the number of response discontinuities. PMID- 4044136 TI - Hemispheric differences in the perception of positive and negative faces. AB - Thirty-two right-handed subjects (15 males and 17 females) participated in a study investigating the effects of the perception of positive and negative emotional stimuli on choice reaction time. Slides of faces showing positive (happy, surprise) or negative (anger, disgust, sadness) affect were presented via a tachistoscope to either the right or left visual field. A 2 X 2 X 2 X 2 mixed analysis of variance with repeated measures over the factors of hand used by visual field by affect across sex of subject revealed a main effect for visual field (with slightly faster responses to stimuli presented in the right visual field) and a strong affect by visual field interaction with positive facial slides identified more quickly than negative facial slides when presented to the right visual field. PMID- 4044137 TI - An investigation of hemispheric asymmetry in size and semantic discriminations and related visual ERPs. AB - The present study examined possible hemispheric differences in discriminations of different sizes of geometric shapes (rectangles) and different meanings of words, and determined whether left and right hemisphere derived visual event related potentials (ERPs) were related to performance. Eighteen right-handed subjects (10 male and 8 female) participated in two separate sessions conducted on different days. The visual ERPs were recorded from over left parietal (P3) and right parietal (P4) scalp locations. Subjects were required to make discriminations of three words (PARE, PAIR, PEAR) and three sizes of rectangles (small, medium, large). Each word and rectangle was singly presented for 40 msec at 1 degree 24 minutes of arc to the left and right of central fixation (LVF and RVF respectively). The major findings were as follows: 1) there were no performance and ERP differences between hemispheres in the verbal task; 2) the left hemisphere excelled in the spatial task; however, ERPs derived from the two hemispheres were similar; 3) subjects experienced greater difficulty in their discriminations of geometric size, as compared to words, regardless of field of presentation. Discrimination of size seemed to have influenced P3 (P300) latency, i.e., it was longer (both hemispheres) when subjects made size discriminations as compared to words. It was proposed that the more difficult discriminations involved in size discrimination required a greater time for stimulus evaluation and that this was reflected in the delayed P3 response. PMID- 4044138 TI - Abnormal electrophysiological responses to successive stimuli in patients with cortical damage or multiple sclerosis. AB - We studied the cortical potentials of normal subjects and patients with unilateral hemisphere damage to two simultaneous or successive stimuli. Both groups showed variations in the interaction between the signals evoked by the stimuli as a function of interstimulus interval. However, the anomalous stimulus response function obtained from the patient group suggests pathological signal interaction. Data obtained from patients with multiple sclerosis were similar to those of the cortical-injury group suggesting that localized cerebral damage is not requisite for the disturbed profiles. We hypothesize that the results indicate abnormal temporal processing by these patients and propose that the defect may underlie visual illusions reported by patients with cerebral pathology. PMID- 4044139 TI - Radiolabeled L-fucose for diagnostic oncology: preliminary studies in mice and rats using L-1-14C-fucose. PMID- 4044140 TI - Relation between the location of elements in the periodic table and tumor-uptake rate. AB - The bipositive ions and anions, with few exceptions, indicated a low tumor uptake rate. On the other hand, compounds of Hg, Au and Bi, which have a strong binding power to protein, showed a high tumor uptake rate. As Hg2+, Au+ and Bi3+ are soft acids according to the classification of Lewis acids, it was thought that these ions would bind strongly to soft bases (R-SH, R-S-) present in tumor tissue. For many hard acids such as 85Sr2+, 67Ga3+, 181Hf4+, and 95Nb5+, tumor uptake rates are shown as a function of ionic potentials (valency/ionic radii) of the metal ions. Considering the present data and previously reported results, it was presumed that hard acids of trivalence, quadrivalence and pentavalence would replace calcium in the calcium salts of hard bases (calcium salts of acid mucopolysaccharides, etc.). Ionic potentials of alkaline metals and Tl were small, but the tumor-uptake rate of these elements indicated various values. As Ge and Sb are bound by covalent bonds to chloride, GeCl4 and SbCl3 behaved differently from many metallic compounds in tumor tissue. PMID- 4044141 TI - Protein-binding and urinary excretion of 99mTc(Sn)-MDP and 99mTc-MDP. AB - In an incubation experiment the Human Serum Albumin (HSA) binding of 99mTc-MDP (electrolytically labeled) and 99mTc(Sn)-MDP is established. During the incubation some pertechnetate is formed and in the case of 99mTc(Sn)-MDP also some hydrolyzed 99mTc. The HSA binding of 99mTc-MDP is less than the HSA binding of 99mTc(Sn)-MDP as established with gel chromatography, TCA-precipitation, ammonium sulfate precipitation and ultrafiltration. TCA-precipitation seems to be an insufficient method for determining the protein binding of 99mTc(Sn)-MDP. The urinary excretion in rats shows only one 99mTc-compound in both cases. The bone seeking properties of the urine-excreted 99mTc-compound were confirmed in another rat. PMID- 4044142 TI - Biodistribution of [14C]PnAO in rats. AB - The biodistribution of [14C]3,3'-(1,3-propanediyldiimino)-bis(3-methy 1-2 butanone)-dioxime, [( 14C]PnAO) was determined in anesthetized rats. The results of this study show that there is no significant brain accumulation or retention of the uncomplexed ligand in the brain. PMID- 4044143 TI - Lymphomatous intracardiac mass detected by radionuclide ventriculography. AB - A case of non-Hodgkin's lymphocytic lymphoma with cardiac involvement shown as an intracardiac-filling defect on the radionuclide ventriculogram is presented. The non-invasive diagnostic methods for cardiac lymphoma work-up are discussed. The known causes of cardiac-chamber filling defect(s) are reviewed. PMID- 4044144 TI - Distribution and mechanism of uptake of 111InCl3 in a tumor model for lymph node metastases. AB - The localization of 111In activity in the tumor and draining lymph nodes of the H 4-II-E ACI rat hepatoma was investigated following the injection of 111In chloride. In this tumor model, the tumors metastasize to the regional lymph nodes in male rats only. The following experiments were performed: (a) biodistribution of 111In; (b) correlation of 111In uptake with [3H]thymidine; (c) gamma camera imaging; (d) autoradiography; (e) iron competition and (f) binding of 131I transferrin to H-4-II-E cells. Tumor-to-muscle ratios of 111In in males were 4.9:1 in the primary tumor and 9.1:1 in the metastatic lymph nodes 24 h post injection. In the lymph node metastases in the males, a significant correlation between 111In uptake and [3H]thymidine was observed (r = 0.737) suggesting that 111In uptake in the metastases is related to cellular proliferation. No such correlation was observed in either primary tumors (both male and female) or in the draining lymph nodes of the females. Metastatic lymph nodes in males could be detected in gamma camera images while draining nodes in females could not be delineated. Injection of ferric citrate prior to 111In administration resulted in a significant reduction of 111In uptake in the liver, spleen and tumor and increased the amount of activity recovered from the kidney. Measurements of the binding of 131I-labeled rat transferrin to H-4-II-E cells in vitro suggest that these cells display transferrin receptors. PMID- 4044145 TI - Benzydamine: a new therapeutic concept for the treatment of inflammation. Proceedings of a symposium presented at the 1st World Conference on Inflammation, Antirheumatics, Analgesics, Immunomodulators. Venice, Italy, 16-18 April 1984. PMID- 4044146 TI - Aspects of the mechanisms of action of benzydamine. AB - Benzydamine shows some properties that are common with other nonsteroidal antiinflammatory drugs (NSAIDs) but displays also properties which are different from those of other NSAIDs. It inhibits prostaglandin and thromboxane biosynthesis at high concentrations, which however can be reached by topical application of the drug. It has no inhibiting effect on amino-acid decarboxylases, which are inhibited by various NSAIDs. Benzydamine has no effect on sulphydryl-group reactivity, contrary to most NSAIDs. It inhibits platelet aggregation and the inhibition of the collagen-induced aggregation appears to be rather selective with respect to other NSAIDs. It displays a stabilizing effect on erythrocyte membranes which appears related to its high affinity for membranes in general, and it inhibits the respiratory burst of stimulated human monocytes and granule enzyme release by human neutrophils. PMID- 4044147 TI - Pharmacokinetics of benzydamine. AB - Clinically, benzydamine can exert its action locally or systemically. Consequently the pharmacokinetics of this drug have been studied after its administration by several different routes. Oral doses of benzydamine are apparently well absorbed and plasma drug concentrations reach a peak fairly rapidly (e.g. 0.8 micrograms/ml after a 100-mg dose) and then decline with a half life of about 13 h. Less than 20% of the drug is bound to plasma proteins. Assuming complete oral systemic availability, values of 193 ml/min and 213 litres respectively were calculated for the systemic clearance and volume of distribution of benzydamine. Cutaneous doses of benzydamine are more slowly absorbed and lead to peak drug levels about three-fold lower, but more persistent than those after oral administration. Although local drug concentrations are relatively large, the systemic absorption of mouthwash-gargle, vaginal and rectal doses of benzydamine is relatively low compared to oral doses: this lower absorption should greatly diminish the potential for any systemic drug side effects when benzydamine is administered by these routes. Benzydamine is metabolized primarily by oxidation, conjugation and dealkylation. PMID- 4044148 TI - Benzydamine cream in post-traumatic oedema. AB - The therapeutical effect of drugs for ankle distortions was quantified by a volumetric method and by load distribution during walking. The results obtained were comparable and showed that 5% benzydamine cream was very effective in the reduction of oedema of post-traumatic origin. PMID- 4044149 TI - Behaviourism and clinical psychiatry. PMID- 4044150 TI - Guilt feelings and locus of control of concentration camp survivors. AB - The present study compared concentration camp survivors and controls from the same ethnic and religious background on two variables: guilt feelings in everyday life and locus of control. No significant differences were found between survivors and controls. As for sex differences, it was found that women expressed significantly more guilt than men in "behaviors contrary to moral or ethical principles" and men were significantly more internal than women. The implications of these findings were discussed. PMID- 4044151 TI - Community psychiatry and it's discontents. PMID- 4044152 TI - Cultural phenomenology and residency training revisited: a personal account. AB - A field experience in the Northern Galilee area of Israel is described by a Senior American Resident in Psychiatry, with emphasis on the cultural aspects of the experience as well as the benefits related to professional maturation. The author discusses the field experience as part of a residency education, invites other such experiences, and compares his own experiences with others described in the literature. PMID- 4044153 TI - Jungle madness: some observations on expatriate psychopathology. PMID- 4044154 TI - Clinical aspects of cultural psychiatry on Guam. PMID- 4044155 TI - Gender differences in living conditions found among male and female schizophrenic patients on a follow-up study. AB - In four provinces of Canada schizophrenic patients who had received psychiatric treatment not less than 18 months and not more than 10 years earlier, were interviewed. Findings suggest that the female schizophrenic patient, having a later age of onset than the male patient, and being more likely to form a stable spousal union, appears to enjoy a protected status which confers with the benefits of higher income levels, better housing and lessened likelihood of being placed in residential care. A further demonstration of the advantaged circumstances of the female patients may well be their superior showing on functional outcome indicators, where they out-performed males on all indices except physical activity at significant levels of differentiation. PMID- 4044156 TI - Depressive disorders in the developing world. AB - In order to find out whether the finding of different prevalence rates for depression in rural and urban areas of India is supported by a difference in symptomatology as well, 30 rural and 42 urban hospitalized MDP-Depressed patients were compared on Hamilton Depression Scale and Schedule for Standardized Assessment of Patients with Depressive Disorders. Symptoms of guilt, loss of concentration and memory were significantly more in urban patients whereas gastrointestinal somatic symptoms were significantly higher in rural subjects. The difference is probably due to urban subjects being more sophisticated, expressive and familiar with mental disorders as compared to rural patients who being more familiar with somatic illnesses tend to somatize their psychic distress. PMID- 4044157 TI - Attitudes of Turkish and American clinicians and Turkish psychology students toward mental patients. AB - A comparative study of Turkish and American clinicians and first and fourth year Turkish psychology undergraduates was carried out. The respondents' attitudes about the "behavior of a mental patient" were assessed through a semantic differential task. Statistical comparisons showed that the four groups were very similar to each other although there were some significant differences. The possibilities of Western influence, similar groups selecting the fields of psychiatry and psychology, and psychology students forming a special well informed group were discussed. A need for further research to clarify the findings was pointed out. PMID- 4044158 TI - Comparison of depressive symptomatology between Saudi and American psychiatric outpatients in an Eastern Province medical center, Saudi Arabia. AB - This study compares the responses to a self-report depression inventory administered to a sample of 243 Saudi and American expatriate psychiatric outpatients of a large Eastern Province medical centre in Saudi Arabia. The inventory was developed by Beck et al. (1961), and the Arabic language form was validated by West and Al-Kaisi (1982). A Kruskal-Wallis statistical analysis revealed that American male patients tended to be more depressed than American female patients, Saudi female patients reported "depression scores" higher than those of Saudi male patients, and Saudi patients overall reported higher "depression scores" than American patients participating in the same study. The highest and lowest significant response frequencies for Saudis were: Pessimism (H = 74.26) and Hypochondria (H = 17.13); for Americans: Indecisiveness (H = 25.57) and Self-Image (H = 7.85). (Statistical significance when H = 7.82, p less than .05; H = 16.27, p less than .001; df = 3). Although explanations are offered, the appearance of psychopathology as designated by this cross-cultural scale requires further cultural examination. PMID- 4044159 TI - Effects of timolol, epinephrine, and acetazolamide on aqueous flow during sleep. AB - The effects of timolol, epinephrine, and acetazolamide on the rate of flow of aqueous humor through the anterior chamber of awake and sleeping human subjects was studied. Timolol reduced the rate in awake subjects but not sleeping subjects. Epinephrine increased the rate in sleeping subjects to a greater extent than in awake subjects. Acetazolamide reduced the rate of flow in awake subjects or epinephrine-stimulated subjects. Acetazolamide reduced the rate of flow slightly below the basal rate observed during sleep, but the reduction was small and not statistically significant. The authors propose that the diurnal fluctuation of the rate of aqueous humor flow in humans is driven by changes in the concentration of endogenous epinephrine available to the ciliary epithelia. PMID- 4044160 TI - Trabecular meshwork glycosaminoglycans in human and cynomolgus monkey eye. AB - The glycosaminoglycans (GAGs) extractable from the trabecular meshworks (TM) of human and non-human primate eye have been analyzed by sequential enzymatic degradation and cellulose acetate electrophoresis. For comparison, similar extracts of the cornea, sclera, iris, and ciliary body have also been analyzed. The distribution of glycosaminoglycans in human and in cynomolgus monkey TMs are similar, although not identical. The human TM contains hyaluronic acid (HA), chondroitin-4-sulfate and/or 6-sulfate (CS), dermatan sulfate (DS), keratan sulfate (KS), heparan sulfate (HS), and an unidentified band of Alcian Blue staining material, which is resistant to the enzymes that we used. Based upon quantitation of the Alcian Blue staining intensities of extracted GAGs, which have been corrected by a relative dye-binding factor, the GAGs of the human TM include: 29.0% HA, 14.1% CS, 21.5% DS, 20.3% KS, and 15.0% HS. The cynomolgus monkey trabecular GAGs include: 12.8% HA, 14.3% CS, 15.2% DS, 42.1% KS, and 15.6% HS. PMID- 4044161 TI - Superoxide dismutase and catalase of calf trabecular meshwork. AB - Superoxide dismutase and catalase activities have been measured in cell-free extracts of calf trabecular meshwork, and for comparison, in calf iris, retina, lens, liver, and erythrocytes. Gel electrophoresis has been used to identify isozymes of each enzyme. The superoxide dismutase and catalase activities per milligram wet weight of calf trabecular meshwork, 0.184 and 0.884 U/mg wet wt, respectively, were comparable to those found in iris and retina, and much higher than those found in lens. Three isozymes of superoxide dismutase were identified in trabecular meshwork. Two of these presumably correspond to cytoplasmic superoxide dismutase, while the third corresponds to a mitochondrial isozyme. A presumably mitochondrial superoxide dismutase activity was also observed in iris and retina, but not in lens. A single catalase isozyme was found in all tissues examined. At physiologic H2O2 concentrations, catalase may have similar levels of activity to glutathione peroxidase. Superoxide dismutase, catalase, and glutathione peroxidase may constitute an important defense mechanism of trabecular meshwork against the toxic O2-. and H2O2 to which it must be continuously exposed from endogenous production as well as from the aqueous humor. PMID- 4044162 TI - Effects of calcium on the steady outward currents at the equator of the rat lens. AB - The relationships between calcium and the steady outward currents at the equator of the rat lens were studied using the vibrating probe technique. In a calcium free medium, the current was greatly increased and it returned to its original level when calcium was restored to the medium. The Ca-free effect was not observed in Na-free medium. Iodoacetate (IAA) inhibited the initial current, but a current then returned which is referred to as a secondary current. The secondary current was not observed in a Ca-free medium and, therefore, it is thought to be a calcium-dependent potassium current. These responses are consistent with effects on potassium efflux measured by others and lend support to the interpretation that the outward currents observed at the equator of the rat lens are potassium currents. The currents are partially inhibited but not abolished in Na-free bathing medium. This is consistent with the view that the inward currents at the optical poles may be related to the influx of sodium. PMID- 4044163 TI - NMR analyses of the cold cataract. III. 13C acrylamide studies. AB - 13C-enriched acrylamide was employed to further delineate the action of this compound in preventing the cold cataract phenomenon when it is incorporated (in vitro) into young human and rabbit lenses. The extent of acrylamide incorporation, in the dark and with concurrent UV exposure, was monitored by 13C NMR spectroscopy. These studies provide further evidence that UV exposure causes permanent acrylamide photobinding within the lens. In such lenses, the gamma crystallin fraction of the soluble lens proteins is affected to the greatest extent. It appears to become aggregated and/or combined with the alpha and beta fractions resulting in an apparent loss of most of the gamma monomers. There is also an age-related effect with respect to the amount of acrylamide that can be incorporated into the lens. The decrease in acrylamide incorporation with age directly parallels the age-related decline in gamma crystallin levels. PMID- 4044164 TI - Patterns of herpes simplex keratitis in inbred mice. AB - The authors have investigated the course of herpes simplex type 1 (HSV) keratitis in three different inbred strains of mice infected with four different HSV isolates. Severity of ocular disease and mortality is dependent upon both the virus isolate and the host strain. In particular, the likelihood of progression from self-limited dendritic keratitis to severe necrotizing stromal keratitis varies markedly among the virus-host strain combinations tested. When mice from strains resistant to stromal disease are crossed with mice from strains susceptible to stromal disease, the F1 offspring are resistant, suggesting that the gene(s) controlling resistance is dominant. Corneal stromal keratocytes and embryo fibroblasts from inbred mice differ significantly in their ability to support the replication of HSV in vitro. HSV replicates more efficiently in vitro in keratocytes from mice susceptible to stromal keratitis than it does in keratocytes from mice resistant to stromal keratitis. These findings provide evidence in an animal model for both virus- and host-related mechanisms that determine susceptibility to stromal keratitis. PMID- 4044165 TI - Zonulae adherentes pore size in the external limiting membrane of the rabbit retina. AB - The interphotoreceptor space (IPS) of the retina is bordered by the retinal pigment epithelium, photoreceptors, and Muller cells and surrounds the photoreceptor outer and inner segments. It contains a matrix composed of glycosaminoglycans and proteins, including interphotoreceptor retinol-binding protein (IRBP). The matrix does not diffuse sclerad through the tight junctions that link cells of the pigment epithelium or vitread beyond the point at which photoreceptors and Muller cells are linked by zonulae adherentes that comprise the external limiting membrane (ELM). Biotinylated protein probes of known Stokes' radius were used to determine the pore size of the ELM. Following exposure of the photoreceptor side of isolated rabbit retinas to each protein, the extent of diffusion of the probe through the retina was determined by avidin D-horseradish peroxidase histochemistry. Each protein with a Stokes' radius of 30 A or less diffused freely through the neurosensory retina while each protein with a Stokes' radius greater than 36 A was blocked abruptly at the ELM. Thus, the pore radius of the zonulae adherentes of the ELM lies between 30 and 36 A, which is sufficiently small to account for containment of IRBP (55 A) within the IPS. This study emphasizes that in addition to providing structural support, the zonulae adherentes of the ELM serve to define an important extracellular space of the retina. This has clinical relevance, since two serum proteins tested, albumin and gamma-globulin, are too large to diffuse through an intact ELM. This may explain why protein-rich fluid accumulates in the IPS when the outer blood retinal barrier is compromised by disease or injury.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4044166 TI - Interstitial retinol-binding protein (IRBP) in the RCS rat: effect of dark rearing. AB - The effect of light- and dark-rearing on the amounts of rhodopsin and interstitial retinol-binding protein (IRBP) in RCS rats and their congenic controls (RCS-rdy+) was determined. Rhodopsin was measured spectroscopically and IRBP by dot-blot enzyme immunoassay utilizing rabbit antibovine IRBP IgG. After P15-20, dark-reared RCS and RCS-rdy+ rats always had more rhodopsin than their light-reared, age-matched counterparts. The rhodopsin in the light-reared RCS rats peaked at about 2 nmol/eye at P20-25. The rhodopsin in the dark-reared RCS rats peaked at about 4 nmol/eye at P60-70. Maintenance of RCS-rdy+ rats in darkness had no effect on their IRBP content, which continued to increase up to P80-110. In both groups of RCS rats, the amount of IRBP reached a peak at P22. In RCS rats maintained in darkness, the amount of IRBP attained at this peak was about twice that in the corresponding light-reared group and in RCS-rdy+ animals at this age. The decline of IRBP after P22 in RCS rats was slowed in darkness by approximately 10 days. This slowed decline of IRBP is associated with a decreased rate of photoreceptor degeneration, and the results are therefore consistent with the hypothesis that the photoreceptors synthesize and secrete IRBP. The layer of membranous debris would restrict the diffusion of IRBP in the subretinal space and could partially exclude this retinol transport protein from access to the zone adjacent to the apical surface of the retinal pigment epithelium (RPE). PMID- 4044167 TI - Glucagon and VIP in the retina. AB - Immunoreactive glucagon and immunoreactive vasoactive intestinal polypeptide (VIP) have been demonstrated in neuronal elements in the retina of a number of species by immunohistochemistry. In the present study, the concentrations of glucagon-like and VIP-like material in retinae from different species were determined by radioimmunoassay. The retinal concentration of glucagon-like immunoreactivity was 10-35 pg/mg in goldfish, chicken, pigeon, and frog, whereas retinae from cow, pig, rabbit, and rat contained very little. Retinae from the latter four species were on the other hand rich in VIP-like material whereas retinae from cat, guinea pig, and goldfish contained very little. The glucagon like immunoreactive material in chicken and frog retina was subjected to gel chromatography and high performance liquid chromatography (HPLC). The results indicate that the extracted protein is of similar molecular size as porcine pancreatic glucagon, distinct from porcine glicentin. VIP immunoreactive material extracted from bovine retina was similar in molecular size as authentic porcine VIP by gel chromatography. PMID- 4044168 TI - Effect of laser photocoagulation on oxygenation of the retina in miniature pigs. AB - A large area of the posterior pole of the retina of the miniature pig was photocoagulated, and 2-3 wk later the PO2 in the preretinal vitreous was mapped with O2-sensitive microelectrodes. In the control retina, the PO2 was highly heterogeneous being much higher close to an artery than opposite an intervascular zone. After photocoagulation, PO2 opposite an intervascular zone was found to be significantly increased. A quantitative histologic analysis showed that in the photocoagulated areas more than 28% of the outer retina was destroyed. The authors conclude from these results that photocoagulation, by partially destroying the pigment epithelium-photoreceptor complex, causes an increase of the oxygenation of the retina. PMID- 4044169 TI - Anterior optic nerve blood flow in experimental optic atrophy. AB - This study attempts to establish whether neurogenic optic atrophy induces changes in anterior optic nerve circulation and to determine how noninvasive techniques of measuring blood flow in vivo compare to microsphere distribution. Five cats underwent unilateral optic nerve transection in the orbital apex and a sham procedure in the contralateral eye. Two to three months later, no abnormalities were detected by fluorescein angiography. Laser Doppler measurements demonstrated a 53% decrease in red blood cell speed through the capillaries of the atrophic optic nerve heads in vivo. Optic disk reflectance measurements of anterior optic nerve blood volume in vivo demonstrated a 51% decrease in the estimated blood volume of the capillaries in atrophic optic nerve heads. Flow was calculated on the basis of these noninvasive measurements and demonstrated an average decrease of 74% in optic atrophy. Histologic studies of microsphere distribution demonstrated an average decrease of 80% in flow to the anterior optic nerve in optic atrophy. These results suggest that anterior optic nerve blood flow is significantly reduced in primary neurogenic optic atrophy. This study also demonstrates that the noninvasive measurements of blood flow are substantiated by histologic evaluation of microsphere distribution. PMID- 4044170 TI - Experimental myopia in chicks: ocular refraction by electroretinography. AB - Application of devices that degrade the retinal image has been reported to produce enlargement of the ocular globe in young domestic chicks. Two such device types (domes and arches) were applied to 3-day-old chicks. The domes affected the entire visual field whereas the arches affected only the lateral field. A third group wore a thin circumorbital ring to control for possible mechanical impediments to growth. Untreated control chicks comprised a fourth group. At ages ranging from 3 to 7 wk, the chicks were refracted in their lateral visual fields with a Maxwellian view optometer based on Scheiner's principle, which yields an objective assessment of the refractive state of the photoreceptor image plane. One to seven measurements were taken from each of 48 urethane-anesthetized chicks. These indicated that the mean refractive states of the untreated eyes and the ring eyes were -0.20 D and -0.19 D, respectively, which did not differ significantly from emmetropia. In contrast, the mean refractive states of the arch eyes and the dome eyes were -4.11 D and -14.88 D, respectively, which differed significantly from emmetropia and from each other. The results indicate that early retinal image degradation can result in the relatively rapid development of a substantial myopia in these experimental animals. PMID- 4044171 TI - Nonselective losses in foveal chromatic and luminance sensitivity in multiple sclerosis. AB - A psychophysical technique involving simple increment threshold measurements was used to determine foveal chromatic and luminance sensitivity in patients with multiple sclerosis (MS) and in matched normal controls. The patient group showed substantial and nonselective losses in chromatic and luminance sensitivity relative to the normal control group, and these losses were significantly correlated with each other over individual patients. It is suggested that impairment of foveal visual function due to demyelination is not more specific to fibers carrying chromatic information than to fibers carrying luminance information. PMID- 4044172 TI - Stereochronometry: quantitative measurement of optic disc cup changes. AB - The authors have developed an objective, quantitative method for detecting optic disc cup changes that occur with time. Called stereochronometry, this new technique uses a stereoplotter to measure changes recorded in the combination of two single photographs taken of the same optic disc at different times. The reproducibility and sensitivity of stereochronometry were evaluated using a model eye. Stereochronometric measurements were significantly correlated with calibrated changes of depth and width of the cup of the model eye. Standard deviations for five measurements of cup changes without camera shift range from 2 microns to 18 microns, and errors (deviations of the mean of measurements from calibrated cup changes) ranged from -26 microns to +33 microns. Standard deviations and errors in the measurement of cup depth and width were significantly increased when the camera was shifted by 2.5 mm between photographs to simulate possible changes in photographic conditions. PMID- 4044173 TI - In vitro contractility of avascular corneal wounds in rabbit eyes. AB - Contraction of corneal wounds has been the topic of recent speculation, particularly in reference to regression of corneal flattening following radial keratotomy. In an animal model of corneal wound fibroplasia, we offer the first demonstration of in vitro contractility by avascular corneal wound tissue. Three millimeter diameter full-thickness corneal trephine wounds were made in 17 New Zealand white rabbit eyes. The animals were killed and specimens were extracted 3 4 wk postinjury. Contractile responses of corneal wounds were measured on a microdynagauge force transducer. When exposed to serotonin, epinephrine or norepinephrine corneal wounds showed contractions reaching maximum force of 20 100 mg with a peak response obtained within 5-10 min and persisting several hours. Normal corneas did not respond to any agent. All normal iris muscle specimens contracted to acetylcholine exhibiting peak responses of 30-60 mg of force within 5 sec decaying over the following 10-20 min. This is different from corneal wounds which fail to respond to acetylcholine (P less than 0.005). These data suggest that avascular corneal wounds possess contractile properties. PMID- 4044174 TI - RPE cells and choriocapillaris atrophy. PMID- 4044175 TI - Anterior chest wall mass in an elderly male. AB - A case of chondrosarcoma arising from the right anterior second rib in an 84-year old man is described. Radiographic features include amorphous calcification within a chest wall mass. CT findings include calcification and necrosis within the 8 X 8 X 10 cm tumor, and extension into the adjacent lung. The presence of zones of dedifferentiation into fibrosarcoma in the surgically resected tumor indicates a poor prognosis, with a high likelihood of early recurrence and pulmonary metastasis. PMID- 4044176 TI - Quantification of contrast in clinical MR brain imaging at high magnetic field. AB - The relative contrast between two tissues in a magnetic resonance (MR) image is shown to be quantifiable for any combination of pulse timing parameters, provided the intrinsic parameters are known. Based on multiple inversion-recovery and spin echo images, a region-of-interest T1, T2 and density analysis was conducted at 1.4T in selected patients with diagnosed neuropathology for various brain tissues. The resulting tissue parameters subsequently served to calculate the contrast-to-noise (C/N) ratio for typical tissue interfaces as a function of the operator-variable pulse timing parameters and the data were compared with the images. Although such calculations may be useful as a protocol selection aid, it is obvious that an optimized pulse protocol can only be established for a single tissue interface. The data also reveal that a T2-discriminating pulse sequence like Carr-Purcell-Meiboom-Gill with long repetition time, generally advocated as clinically most effective, may not always be ideal. PMID- 4044177 TI - Comparison of I-123 IMP cerebral uptake and MR spectroscopy following experimental carotid occlusion. AB - Both I-123 IMP scintigraphy and MRI have been suggested as sensitive detectors of changes shortly after acute cerebral infarction. We compared the uptake of N isopropyl I-123 p-iodoamphetamine (IMP) and MR spectroscopy of the brain after internal carotid artery ligation. Thirteen gerbils were lightly anesthetized with ether. After neck dissection, an internal carotid artery was occluded. After 2.8 hours, 100 muCi I-123 IMP was injected intravenously into the 13 experimental animals plus three controls. Seven gerbils remained asymptomatic while six developed hemiparesis. At 3 hours after ligation, the animals were killed. The brains were bisected and T1 and T2 relaxation times were determined for the right and left hemispheres by MR spectroscopy immediately after dissection. I-123 IMP uptake was then determined in the samples. Interhemispheric differences in uptake for I-123 IMP were 0.1 +/- 1.7% (SEM) in the control, 33.5 +/- 10% in the asymptomatic and 54.6 +/- 9.7% in the symptomatic animals. Significant differences were seen with I-123 IMP in 6/7 asymptomatic and 6/6 symptomatic animals. In conclusion, I-123 is more sensitive than T1 or T2 relaxation times for the detection of cerebral perfusion abnormalities. Prolongation in T1 and T2 relaxation times correlates closely with increased brain tissue water content and the development of symptoms, indicators of structural brain damage and probable infarction. PMID- 4044178 TI - Extracalvarial soft tissues in cranial computed tomography. Normal anatomy and pathology. AB - Computed tomography has emerged as the modality of choice for imaging soft tissues of the face and neck. However, the extracalvarial soft tissue anatomy has not been delineated. The CT appearance of normal anatomy and variants, including the cutaneous and subcutaneous tissues, muscle layers, and subgaleal space is described. A pathologic spectrum that includes congenital, inflammatory, traumatic, and neoplastic lesions is presented. When appropriate CT windows for viewing the extracalvarial soft tissues are utilized, significant clinical information may be provided. PMID- 4044179 TI - MR imaging parameters in the study of lung water. A preliminary study. AB - The use of magnetic resonance (MR) to evaluate lung water is made difficult by several factors: paucity of proton signal from normal lung, respiratory and cardiac motion, and long relaxation times of lung fluids. To optimize scanning parameters for this use, and to test MR's ability to detect and quantitate regional and temporal variations in signal intensity in hydrostatic pulmonary edema, in vivo experiments were performed with a 0.5 tesla whole body MR imaging device. Human volunteers were studied in prone and supine positions using spin echo technique (TE = 30 msec) with varying TR, and with respiratory and cardiac gating. In addition, sedated, intubated, chronically prepared sheep were paralyzed to control extraneous motion and allow the use of a high frequency ventilator, thereby eliminating respiratory gating. Elevated pulmonary hydrostatic pressure was induced in these sheep by inflation of a left atrial balloon. Relative signal intensity from the lung rises with lengthening TR. Cardiac gating diminishes motion artifact, but masks extravascular water by enhancing signal from slowly flowing blood by an average of 44%. A gravity dependent gradient of signal intensity predictably shifts in supine and prone positions. The use of longer TRs, respiratory gating, and cardiac gating all proportionally prolong data acquisition times to an objectionable degree. Without the use of gating, a gradual rise in relative signal intensity is seen in the sheep lung following the establishment of elevated hydrostatic pressure in the pulmonary circuit, and is most pronounced in the dependent portion of the lung.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4044180 TI - The etiology and implications of dense cavitary "photopenia" on myocardial perfusion scintigraphy. AB - Dense cavitary "photopenia" was observed on 21 of 200 consecutive stress perfusion scintigrams. A prominent finding in many cases, it sometimes occupied only a portion of the region overlying the ventricular cavity, was often seen in some projections and not others, and was frequently adjacent to myocardial perfusion defects. To distinguish an etiology among reduced cavitary radioactivity, relatively increased background radioactivity, or reduced radioactivity in overlying myocardium, quantitative analysis of cavitary, lung and myocardial radioactivity was performed in patients with dense cavitary "photopenia," with and without lung uptake, and compared with results from studies showing increased lung uptake without cavitary photopenia and with normal studies. The results showed that dense cavitary photopenia was related to reduced radioactivity in overlying myocardium. Correlative imaging studies performed with echocardiography and contrast ventriculography confirmed this relationship to myocardial scar in 15 of 21 patients in whom associated akinesis or dyskinesis was seen. Hence, dense cavitary photopenia on stress perfusion scintigraphy is due to a dense myocardial perfusion abnormality, and is often indicative of related scar and an associated severe contraction abnormality. PMID- 4044181 TI - Transcatheter sclerosis of the gallbladder in rabbits. A preliminary study. AB - Catheter sclerosis of 56 rabbit gallbladders was attempted at laparotomy. The proximal cystic duct was occluded with a hemoclip and transcatheter administration of six different sclerosing agents and a saline control was performed. Eight animals were used for each agent, three being sacrificed after two weeks and the remainder after six weeks. Hot contrast and sotradecol were comparable with saline in their lack of effect on gallbladder mucosa. Alcohol alone, tetracycline, methylcyanoacrylate and alcohol plus trifluoroacetic acid were successful at two weeks in denuding the gallbladder epithelium and promoting fibrosis of the gallbladder wall. After six weeks, evidence of mucosal regeneration was present with all agents, and the epithelium appeared to have grown back from the occluded cystic duct. Late regeneration has not been previously reported and its significance when considering the application of the technique to the human gallbladder is discussed. PMID- 4044182 TI - Comparison of diatrizoate, iopamidol, and ioxaglate for arterial portography. An experimental study in normal dogs and dogs with portal hypertension. AB - Diatrizoate, iopamidol and ioxaglate were compared in five normal dogs and in five dogs with presinusoidal cirrhosis and portal hypertension for arterial portography. After selective injection of 40 ml of each contrast agent in iodine concentrations of 320 mg per ml into the superior mesenteric artery, portal vein blood samples were collected in 2-second intervals and the iodine concentrations determined using x-ray energy spectrometry. The highest iodine concentrations in the portal blood were found in both normal portal pressure and portal hypertension with ioxaglate, followed by iopamidol and diatrizoate in this order. Compared with diatrizoate, ioxaglate and iopamidol increased the peak portal blood iodine concentrations 45% and 22%, respectively. The use of ioxaglate in arterial portography should show the portal system at least as well as when a conventional contrast agent is used together with a vasodilator such as tolazoline. PMID- 4044183 TI - Correlation between portal blood iodine concentrations and radiographic visualization of the portal vein in arterial portography. AB - Portal blood iodine concentrations and the radiographic visualization of the portal vein were compared in five dogs (50 portograms). The portal blood iodine concentrations required for a certain degree of portal vein opacification varied considerably. However, an overall significant difference was found in the portal blood iodine concentrations of different degrees of portal vein visualization. An increase in the portal blood iodine concentrations from 0 to 30 mg per ml was associated with an overall improvement of the portal vein visualization. With a blood iodine concentration of 30 mg per ml, an excellent visualization of the portal system was always achieved that could no longer be improved by further increasing the portal blood iodine concentration up to 50 mg per ml. For a reliable diagnostic visualization of portal vein contributaries and branches, a blood iodine concentration of 30 mg per ml appears required; whereas for the visualization of the larger portal vein, 15 mg per ml appears sufficient. PMID- 4044184 TI - Ultrastructural changes in rat aortic endothelium during contrast media infusion. AB - A rat model was employed to investigate contrast media (CM) induced ultrastructural changes in the vascular endothelium. Ionic contrast materials such as Renografin-76 (diatrizoate meglumine diatrizoate sodium), MD-76 (diatrizoate meglumine diatrizoate sodium), and Angiovist (meglumine diatrizoate) were injected into the femoral vein of anesthetized male Wistar rats (240-260 g) and allowed to circulate. Control animals were similarly injected with equiosmolar sucrose and physiologic saline. The thorax was opened 15 minutes, 1 hour, and 4 hours postinjection and cardiac perfusion performed using Karnovsky's fixative; the thoracic aorta was then surgically removed, and processed for transmission electron microscopy. All CM produced shrinkage in cell cytoplasm and nuclear structures thereby causing distortions in cell morphology. In control tissues, however, no such ultrastructural damages were noted. Within 15 minutes of CM infusion, electron dense granules were seen on the luminal surface of endothelial cells, in pinocytotic vesicles, as well as in the gap junctions between cells. These observations indicate that contrast media intake occurs via vesicular transport, and through the cell junction. PMID- 4044185 TI - Policies and attitudes toward the pregnant radiology resident. AB - To evaluate attitudes and policies toward pregnant radiology residents, a questionnaire was sent to the chiefs of radiology residency programs across the country. A return rate of 76.4% and a response rate of 75.4% were achieved. A large majority of the respondents indicated that schedule changes would be made to avoid excessive exposure of a pregnant resident to radiation. The accommodations they suggest are reviewed, and suggestions are made that would help alleviate some of the stress and conflicts that invariably arise when a resident becomes pregnant. PMID- 4044186 TI - Organ system radiology. Instruction of sophomore medical students. AB - During a six-year period we have evolved a method of teaching organ system radiology to sophomore medical students. This involves didactic and clinical sessions with small group discussions and activities central to the program. The course is designed to present a bridging course between the basic medical sciences and the clinical sciences and to better prepare students for their patient care responsibilities. PMID- 4044187 TI - The development of radiologic schemata through training and experience. A preliminary communication. AB - Research underway in our laboratory suggests that radiologists may develop a visual representation of a prototypical radiograph (a schema) in the course of clinical training. This schema appears to guide radiologists' interpretations of chest radiographs. Cognitive psychologists have demonstrated schematic processing for familiar events or scenes. In our experiments, experienced radiologists (18.5 years average experience), junior staff radiologists (3.5 years), and first-year radiology residents participated in a simple recognition/memory test of chest radiographs. The test phase followed a training phase in which each radiograph was viewed for 500 milliseconds. Both abnormal and normal chest radiographs were used. Correct responses were recorded during the test phase for measuring recognition memory. Residents showed no significant difference in memory between normal and abnormal films. Observers with greater radiologic experience exhibited poorer memory for normal films and better memory for abnormal films compared with less experienced observers. We hypothesize that the development of radiographic schemata as a result of experience accounts for these findings. PMID- 4044188 TI - Lessons in leadership from literature: a sabbatical experience. PMID- 4044189 TI - Hypertension in a patient with multiple renal and adrenal masses. PMID- 4044190 TI - The detection of inflammation in collapsed lung by alterations in proton nuclear magnetic relaxation times. AB - The purpose of this study was to establish the proton NMR relaxation times of collapsed but otherwise normal lung tissue and to determine whether an inflammatory process within a collapsed lung can be detected by alterations in relaxation times. The lungs of three groups of rabbits were studied: group A (n = 7) had a sterile collapse of one lung for two days. The two other groups also had one lung collapsed, but with bacterial (group B, n = 6) or chemically induced (group C; n = 6) pneumonitis superimposed. The contralateral lung, which was acutely deflated at the time of thoracotomy, served as a control in each animal. T1, T2 and the total water content were measured on freshly excised lung samples. In group A, there was no significant difference in T1 (606 +/- 14* ms vs. 595 +/- 18 ms;* = SEM) or T2 (80.6 +/- 1.7 ms vs. 78.4 +/- 2.6 ms) between the collapsed and the control lung tissue. In each animal in groups B and C, T2 was longer in the collapsed lung with superimposed pneumonitis than in the control lung tissue (group B: 116.8 +/- 6.9 ms vs. 82.9 +/- 1.8 ms, P less than .001; group C: 120.5 +/- 5.9 ms vs. 86.0 +/- 1.5 ms, P less than .001). T1 changes were similar, but less marked. There was a linear relationship between the relaxation times and the total water content of the lung samples (T1:r = 0.87; T2:r = 0.91). It is concluded that proton NMR may have a potential in detecting disease such as inflammation in collapsed lung tissue based on differences in relaxation parameters compared with normal lung areas. PMID- 4044191 TI - Regional myocardial blood flow, edema formation, and magnetic relaxation times during acute myocardial ischemia in the canine. AB - This study was designed to measure early changes in myocardial perfusion after acute coronary occlusion, and to examine the relationships among blood flow, myocardial edema, and magnetic relaxation times of ex vivo myocardial tissue. In ten dogs, the left anterior descending coronary artery was occluded for 4 hours prior to sacrifice of the animals. Regional myocardial blood flow was measured using radiolabeled microspheres (15 micron), which were injected into the left atrium 5 minutes prior to sacrifice. Multiple subendocardial tissue samples from the left ventricular free wall were obtained for measurement of magnetic relaxation times, percent water content and tissue radioactivity. Mild, moderate, and severe ischemia were defined as reductions in myocardial blood flow to 30% to 50%, 15% to 30%, and less than or equal to 15% of control, respectively. Myocardial water content was increased with mild ischemia (79.6 +/- 0.7%), moderate ischemia (79.9 +/- 0.4%), and severe ischemia (80.3 +/- 0.6%), all P less than .005 vs. control. T1 relaxation times rose with mild (544 +/- 10 msec, P less than .005 vs. control), moderate (543 +/- 11 msec, P less than .005 vs. control), and severe ischemia (574 +/- 10 msec, P less than .001 vs. control). T2 relaxation times behaved in a similar manner, being prolonged in the mildly, moderately, and severely ischemic groups (38.3 +/- 0.3, 38.1 +/- 0.3 and 38.2 +/- 0.3 msec, respectively; all P less than .001 vs. control).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 4044192 TI - In vitro testing for the risk of arachnoiditis from myelographic contrast media. AB - The risk of arachnoiditis from aqueous myelographic contrast media has been assayed reliably only in experimental animals. The effect of contrast media on protein and collagen production by fibroblasts in vitro was studied. Iocarmate, metrizamide, and iopamidol added to the culture medium caused cells to produce more protein and collagen. The degree to which the contrast medium stimulated collagen production correlated with the risk of arachnoiditis from the intrathecal use of the contrast medium. In vitro testing appears to be an effective assay for arachnoiditis. PMID- 4044194 TI - Combined use of magnetic resonance imaging (MRI) and spectroscopy (MRS) by whole body magnets in studying skeletal muscle morphology and metabolism. AB - As a pilot study, 31-P-spectra of the quadriceps femoris muscle (1.5T) and proton images of the right thigh (.5T) were performed in two cyclists (T) and two untrained (UT) subjects. During ischemia, while MRI did not show any change, phosphocreatine (PCr) concentration decreased and inorganic phosphate (Pi) increased. Recovery occurred within 3 minutes. Ergometric bicycle tests were performed outside the magnet. Submaximal workload (UT 150W/T 260W, 3.5 minutes) caused transient minimal changes in phosphorus metabolites. Supramaximal, partially anaerobic exercise (UT 320W/T 350W, 3.5 minutes) induced similar changes in heart rate, oxygen uptake rate, and plasma lactate in both groups. Decrease of the PCr/Pi ratio, however, was more pronounced in UT subjects and clearly lasted longer. If methodical problems can be resolved, combined MRS and MRI in whole body magnets may become a standard noninvasive modality, adding unique information on morphology (organ volume) and local metabolism to classic mechanical and global physiologic data. PMID- 4044193 TI - Dual-energy projection radiography in the evaluation of femoral neck strength, density, and mineralization. AB - Two different dual-energy projection radiography techniques were utilized in an attempt to predict femoral neck strength, bone density, and bone mineral content in 19 pairs of cadaver specimens. Positive simple linear correlation was observed between dual-energy scanned projection measurements and dry density, ash fraction, cross-sectional cortical bone area and, to a lesser degree, force required for fracture, but not trabecular bone volume, failure time, or Singh trabecular grade. Dual-energy film radiography was found to be a less reliable indicator of femoral neck strength, density, and mineral content. Dual-energy scanned projection results related linearly to mineral-equivalent solution (K2HPO4) concentration, and demonstrated long-term reproducibility in repeated specimen studies. Correction factors derived to account for differences in femoral size and rotation were shown to be reliable over a moderate range of neck projections. Although bone mineral measurement at other sites may provide comparable or greater information concerning hip fracture risk, dual-energy scanned projection radiography appears to be a useful technique for assessment of bone density, mineral content, and strength in the femoral neck. PMID- 4044195 TI - Magnetic resonance imaging of fluorine in rats infused with artificial blood. AB - An MRI pulse sequence has been developed that enables the visualization of a perfluorocarbon (PFC) emulsion in the vascular system of rats. Images were made at 0.12T on a clinical imaging system using a small receiver coil, at intervals of approximately 2 hours, two days, two weeks, and two months after replacement of 50% of total blood volume. The most successful technique produced PA projections of the entire torso for both the fluorine and proton components. Direct comparison allowed identification of PFC in heart, lung, liver, spleen, and large vessels both in vivo and postmortem. Potential clinical applications to vascular imaging are discussed. PMID- 4044196 TI - Enhanced pancreatic CT imaging utilizing a geometric magnification technique. AB - Computed tomography (CT) using a geometric magnification technique was found to improve spatial resolution in phantom studies when compared with conventional third-generation geometry images. The clinical feasibility of using geometric magnification, small focal spot size, and dynamic contrast enhancement was studied in 143 patients referred to CT for clinically suspected pancreatic disease. This population included 46 patients with a normal pancreas and 36 patients subsequently proven to have primary pancreatic carcinoma. Using this new technique in conjunction with dynamic contrast enhancement resulted in high quality pancreatic images. Despite the limitations in tube current associated with a small focal spot size and low total heat capacity of the system, clinical imaging was not adversely affected. Use of the geometric magnification technique is recommended in departments where it is technically feasible. PMID- 4044197 TI - The community hospital radiology clerkship: how should it be structured? Opinions of clinical and university faculty. AB - Michigan State University has a community-hospital-based clinical sciences curriculum. In the past, community program directors have determined radiology clerkship objectives. A survey regarding possible clerkship standardization was distributed to staff radiologists and clerkship coordinators. These radiologists were enthusiastic about standardization of the clerkship, and there was a broad consensus as to the basic elements of an effective clerkship. The university was seen as the source of minimum clerkship standards and of an objective method of evaluation. In response to these requests, basic guidelines for the clerkship have been established. PMID- 4044198 TI - Method to compute arterial blood flow. PMID- 4044199 TI - Boolarra virus: a member of the Nodaviridae isolated from Oncopera intricoides (Lepidoptera: Hepialidae). AB - A small RNA virus with a bipartite genome was isolated from Oncopera intricoides. It was named Boolarra virus (BoV). The particle had a diameter of 30 nm, a sedimentation coefficient of 140S, and a buoyant density of 1.34 g/ml in CsCl. The capsid proteins were examined by SDS-PAGE and consisted of a major species of molecular weight (mol. wt.) 38,000 and a minor one of mol. wt. 40,600. The particle contained 21.2% RNA which was divided between a 22S and a 17S species whose mol. wts. were 1.03 x 10(6) and 0.47 x 10(6), respectively. These properties were comparable to those of the Nodaviridae and established BoV as a member of the family. Serologically, BoV shared antigenic determinants with both Nodamura virus and black beetle virus. PMID- 4044200 TI - Assembly and accumulation sites of maize mosaic virus in its planthopper vector. AB - The morphology, assembly, and accumulation sites of rhabdovirus particles in Peregrinus maidis planthoppers infected with a Hawaiian isolate of maize mosaic virus (MMV) were studied. These particles were usually bullet-shaped, but were sometimes bacilliform, and averaged 234 and 247 nm, respectively, in length and 60 nm in width. They were found in most acini of the principal and accessory salivary glands and in brain, nerve ganglia, leg muscle, foregut, midgut, trachea, epidermis, and fat and connective tissues. In most tissues MMV particles accumulated mainly within intracytoplasmic, dilated cisternae that were connected to the perinuclear space. However, in the salivary glands virus particles accumulated mainly in intercellular and extracellular spaces and were found in secretion vesicles. MMV particles appeared to bud from three types of membranes: (i) inner, and rarely outer, nuclear membranes of cells in most tissues examined; (ii) intracytoplasmic membranes, e.g., endoplasmic reticulum in salivary glands; and (iii) plasma membranes of salivary gland cells and nerve axons. The plasma membrane has not been reported previously as a budding site for plant rhabdoviruses, although it is known as a major assembly site for animal rhabdoviruses. PMID- 4044201 TI - Identity between infectious pancreatic necrosis virus VR-299 and a Chilean isolate. AB - Nucleic acid and protein electrophoretic analyses of the Chilean isolate of infectious pancreatic necrosis virus showed that genomic RNA, as well as the major proteins, were indistinguishable from those of the VR-299 serotype. The data are in good agreement with the theory that the virus was introduced into Chile from North America. PMID- 4044202 TI - Clinical cardiac electrophysiology. PMID- 4044203 TI - The role of sex steroids and sex hormone binding globulin in hirsutism and/or oligomenorrhoea in obese and normal weight women. PMID- 4044204 TI - Reorganisation of blood transfusion policies in elective surgery. PMID- 4044205 TI - Home recording of blood pressure in the management of hypertension. PMID- 4044207 TI - Hospital day care for children. PMID- 4044206 TI - Congenital cutaneous candidiasis and septicaemia treated with miconazole. PMID- 4044208 TI - Rapid intestinal transit and postgastrectomy malnutrition. An experimental study in growing rats. AB - An experimental study was carried out in young, growing rats submitted to total gastrectomy followed by Roux-en-Y esophagojejunostomy (RY) or jejunal loop interposition (JI) to test the role of rapid intestinal transit time in postgastrectomy malnutrition. One to two months postoperatively esophago intestinal transit times were measured and nutrition evaluated by serial body weights. Small intestinal transit times were consistently rapid in the rats submitted to RY reconstruction, in comparison with JI (p less than 0.01). Four months after the operations the growth curves of the three groups (RY, JI and controls) were markedly different. After an initial fall in weight of 33% in the gastrectomized rats, a sizeable increase was observed in the rats with JI (p less than 0.05). This difference in growth may be due to malabsorption and accelerated intestinal transit as a result of bypassing the duodenum after RY. PMID- 4044209 TI - Calcitonin deficit syndrome in thyroidectomized patients. AB - The results of a study carried out on 10 patients who underwent total or subtotal thyroidectomy to determine the effects of a prolonged deficit in calcitonin on bone turnover, are reported. The following parameters were evaluated: serum calcium and phosphate, serum alkaline phosphatase, urinary hydroxyproline, serum iPTH, serum iCT and bone mineral content (BMC) of the distal radius. In ten patients controlled 24 months after surgery, a lowering in circulating iCT levels was noted together with a significant decrease in BMC. These observations while supporting the theory that a CT deficit can determine osteoporosis, suggest that further consideration should be given to substitutive therapies for totally and subtotally thyroidectomized patients. PMID- 4044210 TI - Diaphragmatic hernias due to blunt thoracoabdominal trauma. AB - This nineteen-year retrospective review was designed to evaluate diaphragmatic hernias due to blunt thoracoabdominal trauma in a series of 50 patients. Motor vehicle accidents were the most frequent cause. The diagnosis was made immediately after injury in 34 patients (acute hernias), but delayed from two months to 30 years in 16 (chronic hernias). Two patients, with multiple associated injuries, died soon after admission and diagnosis was made at necropsy. The nature of injury, the physical findings and the plain chest roentgenograms suggested a traumatic diaphragmatic hernia in most of the remaining acutely injured patients. All patients with chronic hernias had suggestive or suspicious abnormalities on chest roentgenograms; however, appropriate upper gastrointestinal tract and barium enema studies were of utmost importance for the correct diagnosis. Reduction of herniated viscera and repair of diaphragmatic defect were generally accomplished through a laparotomy in acute hernias, whereas thoracotomy was the preferred approach in delayed instances. There were four postoperative deaths, three with severe multiple associated injuries and one with respiratory failure. PMID- 4044211 TI - Cancer of the large intestine and previous cholecystectomy: does a relationship really exist? AB - The possible relationship between cancer of the large intestine and previous cholecystectomy has been studied both experimentally and clinically but the results are contradictory. The present study, carried out in 250 patients undergoing intestinal resection for colorectal cancer and in 200 subjects who underwent cholecystectomy more than 10 years previously (with control groups) did not evidence any statistically significant relation (p = 0.2) between cholecystectomy and cancer of the large intestine. On the basis also of data from the literature, the etiopathogenetic hypotheses of the supporters of such relationship are reviewed and the different factors potentially able to explain the discrepancy between the concordant results of experimental studies and the contrasting ones of the clinical and epidemiologic experiences are examined. From the practical point of view, it is felt that a periodic (once a year) clinical and laboratory (guaiac test) control followed, when necessary, by x-ray/and or endoscopic examination should be carried out in all the patients over the age of 40, cholecystectomized since 10 years of longer, especially if females. PMID- 4044212 TI - Relationship of the carcinoma of bile ducts to cholelithiasis. AB - Thirty-eight patients with carcinoma of the bile ducts were studied by PTC and ERCP. These instrumental procedures permit at present a precise and complete diagnosis. In 22 cases (57.9%) the association of a lithiasis was evidenced. The application of a percutaneous transhepatic drainage after PTC in cases of stricture furtherly supports the diagnostic accuracy by the cytologic examination and culture of the bile collected from drainages. PMID- 4044213 TI - Surgical treatment of congenital dilatation of the biliary system. AB - Over a total of 1612 patients undergoing surgery for biliary diseases, in 6 cases a cystic dilatation of intrahepatic bile-ducts suggestive of Caroli's disease was diagnosed. One patient with multiple dilatation of intrahepatic bile ducts and septic shock was treated by external drainage without improvement and died. Two patients were treated by left hepatectomy. One case was treated by right extended hepatic lobectomy. One patient with liver cirrhosis and bleeding oesophageal varices was treated by a distal splenorenal shunt. The last patient showed the association of a choledochal cyst and cystic dilatation of the left intrahepatic bile ducts. She was treated by resection of the cyst and biliary-jejunal anastomosis. Five patients had satisfactory recovery from the operation. They are leading a normal life, and are symptom-free. The different forms of treatment are discussed confirming that the best surgical technique on patients with partial cystic dilatation of bile ducts is liver resection. When the extrahepatic bile ducts are affected, biliary-jejunal diversion is necessary. If a choledochal cyst is present, the removal of the cyst is the most radical approach. When cirrhosis and portal hypertension with bleeding varices are diagnosed, portosystemic shunt is necessary. PMID- 4044214 TI - Carotid body tumors. A report of two cases and review of the literature. AB - Two recently observed cases of carotid body tumor (chemodectoma) are presented. The treatment was subadventitial resection of the tumor with good long-term results. The clinic, diagnostic and therapeutic problems of such tumors are re examined on the basis of the most recent informations obtained from a wide review of the literature. PMID- 4044215 TI - The Moshe Prywes lecture in medical education. Medical education--the search for international eminence and local relevance. PMID- 4044216 TI - Accuracy of endoscopy in the diagnosis of inflamed gastric and duodenal mucosa. AB - Two hundred twenty-three patients underwent upper gastrointestinal endoscopy and biopsy. Correlation of endoscopic and histological findings revealed that a normal gastric and duodenal mucosa could be correctly diagnosed endoscopically in about 80 and 88% of cases, respectively. Duodenitis was diagnosed correctly in 83% of cases; however, the correct endoscopic recognition of gastritis was achieved in only about 50% of the cases. Better results were achieved in "anastomitis," in which the endoscopic diagnosis was correct in 90% of cases. This study supports the view that endoscopy alone should not be relied upon in the diagnosis of gastritis or duodenitis. PMID- 4044217 TI - Treatment of bleeding hemorrhoids by injection sclerotherapy and rubber band ligation. AB - Between March 1981 and September 1982, 178 patients with first- to third-degree bleeding hemorrhoids were treated by injection sclerotherapy and rubber band ligation, as outpatients. Of the treated patients 85 to 90% were asymptomatic during 1 year of follow-up. Complications, ranging from mild to moderate, occurred in only 5.6% of the patients. We conclude that injection sclerotherapy and rubber band ligation, when properly used, are efficient, inexpensive and safe methods for the treatment of bleeding hemorrhoids. PMID- 4044218 TI - Assessment of splenic function in dogs following arterial ligation and autotransplantation. AB - Two methods for the preservation of splenic function following trauma to the spleen were studied and compared in dogs and puppies. One method was splenectomy and autotransplantation of small pieces of splenic tissue, and the other- ligation of the main branches of the splenic artery after partial splenectomy. Dogs subjected to splenectomy alone or laparotomy alone served as controls. Splenic function was assessed on the basis of resistance to sepsis by virulent pneumococci. Cultures were obtained from the blood, peritoneal fluid and intraabdominal organs 3 days after i.v. injection of the pneumococci; none of the adult dogs in any of the groups had positive cultures. Among splenectomized puppies, 55.5% had positive cultures for pneumococci, whereas those which underwent ligation of the splenic artery and partial splenectomy had negative cultures. Microscopic examination of the autotransplants revealed loss of the characteristic structure of splenic tissue, whereas in the dogs in which the splenic artery had been ligated, the spleen showed numerous islands of tissue with well-preserved follicular structure. We suggest that in children with severe splenic trauma, ligation of the splenic artery may provide a promising alternative to splenectomy. PMID- 4044219 TI - Treadmill exercise testing in a middle-aged Jerusalem population sample. The Jerusalem Lipid Research Clinic Prevalence Study. AB - We studied determinants of the exercising physical capacity of 1,640 subjects (1,043 men and 597 women) using the Bruce protocol as modified by Sheffield. These participants represented a sample of parents of 17-year-old adolescents living in Jerusalem. Apparently healthy participants underwent a graded treadmill exercise test (88% of the men and 87% of the women). Exercise was terminated when the subject achieved a heart rate of 85 to 90% of the predicted maximal heart rate or could not continue for other reasons, mainly fatigue or weakness. Exercise performance was assessed according to time on the treadmill. On univariate analysis, duration of exercise was related in both sexes to age, country of origin, reported physical exercise, resting heart rate, systolic and diastolic blood pressure, body mass index and plasma lipids and lipoproteins. In multivariate analysis, time was related to age, body mass index, heart rate and habitual physical exercise in both men and women, and to systolic and diastolic blood pressure in men only. Cigarette smoking and plasma lipid levels were not independently related to time on the treadmill in either sex. Ethnic differences were observed. PMID- 4044220 TI - Behavioral risk factors in adolescence as a basis for health planning. AB - Adolescence has been described as the age when the population is at its peak of health and physical performance. While this may be correct, it is also the age at which the future adult's state of health may be strongly influenced by behavior. It is therefore possible that the identification of behavior patterns that pose a risk to the adolescent (either immediately or for the later development of disease) could form the basis for logical health planning for this age-group. A model has been developed that itemizes the major behavioral risk factors in adolescence and indicates the possibilities for intervention. This model includes the following behavior characteristics: violent behavior (leading to accidents, etc.), cigarette smoking, drug use, sexual intercourse without contraception, the imbibing of alcoholic beverages, the taking of medicines without medical advice, and over- and undereating. The relevance of certain of these practices to the high school dropout phenomenon as a major social problem is emphasized. It is suggested that, on the basis of the model and of knowledge of certain demographic characteristics, risk groups can be identified and relevant health and welfare services planned. PMID- 4044221 TI - Protease inhibitors in sera as possible indicators of familial hypothyroidism. AB - Both synthesis and degradation of proteins are reduced in the hypothyroid state. The possible involvement of serum trypsin and chymotrypsin inhibitors has been studied in a family that, for four successive generations, had clinical or subclinical hypothyroidism. Increased trypsin- and chymotrypsin-inhibiting activity was demonstrated in the sera of the four clinically hypothyroid women. Cellulose acetate electrophoresis of the sera of these patients and of two other subclinical hypothyroid family members disclosed the distinct appearance of an additional fraction in the alpha 2-globulin zone. The serum protein electrophoretic pattern changes observed in familial hypothyroidism might be genetically determined. Such changes could precede the clinical onset of the disease, thus serving as a possible indicator of the hypothyroid state. PMID- 4044222 TI - Amiodarone-induced dysthyroidism. AB - A 54-year-old man, treated with amiodarone, developed thyrotoxicosis. When rechallenged with the same drug 6 months later, he developed hypothyroidism. The therapeutic implications of this clinical sequence are discussed. PMID- 4044223 TI - Legionnaires' disease: new etiologic agents. AB - Two patients with pneumonitis due to legionellosis are described. The etiologic diagnosis was based on high titers of immunoglobulin (Ig)M class antibodies (1/2048 and 1/512) detected by indirect immunofluorescence. The etiologic agents were presumed to be Legionella bozemanii in one case and either L. bozemanii or L. longbeachae in the other. Both patients made an uneventful recovery. Infections with these organisms have not been described in Israel previously. PMID- 4044224 TI - Changing resistance of uropathogens to antibiotics. PMID- 4044225 TI - Erythema multiforme and splenomegaly: an unusual presentation of Mycoplasma pneumoniae infection.